Journal articles on the topic 'API activity recognition'

We propose a system that can recognize daily human activities with a Kinect-style depth camera. Our system utilizes a set of view-invariant features and the hidden state conditional random field (HCRF) model to recognize human activities from the 3D body pose stream provided by MS Kinect API or OpenNI. Many high-level daily activities can be regarded as having a hierarchical structure where multiple subactivities are performed sequentially or iteratively. In order to model effectively these high-level daily activities, we utilized a multiclass HCRF model, which is a kind of probabilistic graphical models. In addition, in order to get view-invariant, but more informative features, we extract joint angles from the subject’s skeleton model and then perform the feature transformation to obtain three different types of features regarding motion, structure, and hand positions. Through various experiments using two different datasets, KAD-30 and CAD-60, the high performance of our system is verified.

Nowadays, not all the patient can be hospitalized because of the COVID-19 pandemics. So, the self-quarantine for the patient with the various diseases will be the given solution by the hospital. It would make the hospital needs a system that can monitor the activity and the position of the patient from a distance. Nowadays, mobile phone is equipped by the sensor that can detect the user movement. Not only the user’s position, but also the user’s activity. In this paper, it will be developed an activity and position monitoring system for the self-quarantine patient that can be used in their home. The mobile activity monitoring can be achieved by activity recognition using classification method. For the needs of performance testing, we evaluate some classification method for activity recognition to compare the among classification method for the activity recognition. Some tested classification methods are Naïve Bayes, KNN, KStar and TreeJ48. Furthermore, we tested the impact of sliding windows per N samples taken to the accuracy of the activity recognition. We choose the best N sample that could give the best accuracy for activity recognition. The system not only monitor the patient’s activity, but also the patient’s position. The position monitoring can be achieved using Google Maps API. The result is Naive bayes has the accuracy of 81.25%, KNN has the accuracy of 78.125%, KStar has the accuracy of 78.125% and TreeJ48 has the accuracy of 75%. The N sample that could give the best accuracy is 6 with the accuracy of 90.15%.

<span>In the world where streets brimmed with vehicles are no longer an foreign sight, vehicle accidents come along as one of unwanted consequences. Accidents are due to many reasons, though however the reason is, most of the times it leads to damaged vehicle(s), injuries or even fatality. In this research, we present Car Safe, a smartphone application which can make phone call reception decision, text readout to prevent distraction, driving time alert and send the location of the driver upon the occurrence of a detected crash. While the Google Activity Recognition API only detects driving state approximately 89% of the time, our proposed method yields more than 93% detection.</span>

AbstractWeb-based browser fingerprint (or device fingerprint) is a tool used to identify and track user activity in web traffic. It is also used to identify computers that are abusing online advertising and also to prevent credit card fraud. A device fingerprint is created by extracting multiple parameter values from a browser API (e.g. operating system type or browser version). The acquired parameter values are then used to create a hash using the hash function. The disadvantage of using this method is too high susceptibility to small, normally occurring changes (e.g. when changing the browser version number or screen resolution). Minor changes in the input values generate a completely different fingerprint hash, making it impossible to find similar ones in the database. On the other hand, omitting these unstable values when creating a hash, significantly limits the ability of the fingerprint to distinguish between devices. This weak point is commonly exploited by fraudsters who knowingly evade this form of protection by deliberately changing the value of device parameters. The paper presents methods that significantly limit this type of activity. New algorithms for coding and comparing fingerprints are presented, in which the values of parameters with low stability and low entropy are especially taken into account. The fingerprint generation methods are based on popular Minhash, the LSH, and autoencoder methods. The effectiveness of coding and comparing each of the presented methods was also examined in comparison with the currently used hash generation method. Authentic data of the devices and browsers of users visiting 186 different websites were collected for the research.

Location Based Service (LBS) is a service to provide information that has been created, compiled, selected or filtered by considering the location of users or other people or current mobile devices [1]. It is possible to implement LBS using GPS because mobile devices have GPS services [6]. Based on these services, making an application for room recognition can be done by utilizing the Google Maps API by implementing GIS, LBS, and GPS. Implementation of application with extreme programming methods is carried out in accordance with the stages. In the planning part, an analysis is carried out on the business needs and user stories, in the design, use case diagrams and activity diagrams are made, coding is done by implementing the design using the mobile programming language, and testing is done using black box testing. The application of LBS is carried out when calling the room information page which functions to find the location of the room and displays notifications and room information when the user enters the radius that has been determined in the room data. Determining the radius is very important to do so that the information about the room that is displayed does not overlap with other rooms. This is done to keep the room information displayed to the user only to display information about one room only. Therefore, when determining the radius of the room, it must be determined carefully so that the radius can create a circle that does not intersect with other radius circles. The room information displayed is obtained from data management by the admin through the building management page, rooms, and items. In managing, admins can add, edit, and delete data.

Location Based Service (LBS) is a service to provide information that has been created, compiled, selected or filtered by considering the location of users or other people or current mobile devices [1]. It is possible to implement LBS using GPS because mobile devices have GPS services [6]. Based on these services, making an application for room recognition can be done by utilizing the Google Maps API by implementing GIS, LBS, and GPS. Implementation of application with extreme programming methods is carried out in accordance with the stages. In the planning part, an analysis is carried out on the business needs and user stories, in the design, use case diagrams and activity diagrams are made, coding is done by implementing the design using the mobile programming language, and testing is done using black box testing. The application of LBS is carried out when calling the room information page which functions to find the location of the room and displays notifications and room information when the user enters the radius that has been determined in the room data. Determining the radius is very important to do so that the information about the room that is displayed does not overlap with other rooms. This is done to keep the room information displayed to the user only to display information about one room only. Therefore, when determining the radius of the room, it must be determined carefully so that the radius can create a circle that does not intersect with other radius circles. The room information displayed is obtained from data management by the admin through the building management page, rooms, and items. In managing, admins can add, edit, and delete data.

In Ambient Intelligence (AmI), the activity a user is engaged in is an essential part of the context, so its recognition is of paramount importance for applications in areas like sports, medicine, personal safety, and so forth. The concurrent use of multiple sensors for recognition of human activities in AmI is a good practice because the information missed by one sensor can sometimes be provided by the others and many works have shown an accuracy improvement compared to single sensors. However, there are many different ways of integrating the information of each sensor and almost every author reporting sensor fusion for activity recognition uses a different variant or combination of fusion methods, so the need for clear guidelines and generalizations in sensor data integration seems evident. In this survey we review, following a classification, the many fusion methods for information acquired from sensors that have been proposed in the literature for activity recognition; we examine their relative merits, either as they are reported and sometimes even replicated and a comparison of these methods is made, as well as an assessment of the trends in the area.

Deep learning (DL) models have emerged in recent years as the state-of-the-art technique across numerous machine learning application domains. In particular, image processing-related tasks have seen a significant improvement in terms of performance due to increased availability of large datasets and extensive growth of computing power. In this paper we investigate the problem of group activity recognition in office environments using a multimodal deep learning approach, by fusing audio and visual data from video. Group activity recognition is a complex classification task, given that it extends beyond identifying the activities of individuals, by focusing on the combinations of activities and the interactions between them. The proposed fusion network was trained based on the audio–visual stream from the AMI Corpus dataset. The procedure consists of two steps. First, we extract a joint audio–visual feature representation for activity recognition, and second, we account for the temporal dependencies in the video in order to complete the classification task. We provide a comprehensive set of experimental results showing that our proposed multimodal deep network architecture outperforms previous approaches, which have been designed for unimodal analysis, on the aforementioned AMI dataset.

Apical membrane sodium hydrogen exchanger 3 (NHE3), a major pathway for non-nutrient-dependent intestinal Na+ absorption, is tightly regulated by second messenger systems that affect its functional activity and membrane trafficking. However, the events and components involved in NHE3 regulation are only partially understood. We report that the adaptor protein synaptotagmin I (Syt I) plays a pivotal role in cAMP- and Ca2+-induced cargo recognition of NHE3 and initiation of its endocytosis. Both mouse small intestine (jejunum) and Caco-2BBe Syt I coimmunoprecipitated with NHE3, particularly following increases in cellular cAMP or Ca2+. Following short interfering RNA (siRNA) suppression of Syt I expression, cAMP- and Ca2+-induced inhibition of NHE3 activity were still observed but NHE3 endocytosis was blocked, as assessed by 22Na influx and apical membrane biotin labeling, respectively. Similar effects on NHE3 inhibition and endocytosis were observed by siRNA suppression of either the μ-subunit of the adaptor protein 2 (AP2) complex or the heavy chain of clathrin. Coimmunoprecipitation analyses of NHE3 with these adaptor proteins revealed that cAMP- and Ca2+-induced NHE3-Syt I interaction preceded and was required for recruitment of AP2 and the clathrin complex. Confocal microscopy confirmed both the time sequence and protein associations of these events. We conclude that Syt I plays a pivotal role in mediating cAMP- and Ca2+-induced endocytosis of NHE3 (but not in inhibition of activity) through cargo recognition of NHE3 and subsequent recruitment of AP2-clathrin assembly required for membrane endocytosis.

Abstract The acute chest syndrome (ACS) is a form of acute lung injury (ALI) unique to sickle cell disease (SCD), and for children >10 years of age represents the major cause of morbidity and mortality. ALI is thought to be neutrophil (PMN)-mediated; however, the pathogenesis of ACS is not known but is linked to an increase of secretory phospholipase A2-IIA (sPLA2) activity within 24 hours of its development (Styles, Blood87:2573, 1996). We hypothesize that sPLA2 cleavage of membrane lipids generates biologically active lipophilic compounds that prime PMNs, which provokes ACS in patients with SCD, resulting in increased lipid priming activity during ACS. After obtaining informed consent, heparinized whole blood was drawn from children with SCD when well, at their annual comprehensive visit, and serially when admitted to the hospital, upon admission and every other day until discharge. Plasma was isolated, and the plasma lipids extracted. In selected patients the plasma was treated with buffer or sPLA2 for 1 hour at 37°C prior to lipid extraction. Lipids were assayed for their ability to prime fMLP-activation of the PMN oxidase as measured by the maximal rate of O2− production by the SOD-inhibitable reduction of cytochrome c at 550 nm. The data (mean ± SEM of fold increase over fMLP-treated controls of the lipid priming activity at baseline and over hospitalization) consists of three groups: patients with SCD, patients with SCD treated with daily hydroxyurea (HU), or patients with SCD treated with monthly, red cell exchanges (EX). At baseline, there was slightly more lipid priming activity in untreated SCD patients versus either HU- or EX-treated patients, which was not statistically different (Table). The lipid activity did not increase with vaso-occlusive crisis (VOC) but significantly increased in the one patient with ACS. Moreover, sPLA2 treatment of the plasma obtained 12 hours prior to developing ACS, while this patient was in VOC, demonstrated an increase in lipid priming activity versus the patient’s prior samples (0.96- to 1.73-fold control with sPLA2). The lipids from healthy African-American patients, did not exhibit increased activity vs controls (data not shown). We conclude that both HU and EX therapies may diminish the baseline activity of plasma lipids as compared to untreated children with SCD. In addition, sPLA2-treatment of the plasma 12 hours prior to the devlopment of ACS increased the amount of bioactive lipids released. Moreover, the amount of lipid priming activity was significantly increased during ACS as compared to baseline and during VOC. These preliminary results support the concept that the pathogenesis of ACS involves sPLA2 activity, which generates bioactive lipids that may provoke ACS, and need to be extended through the recruitment of more patients and completion of a multi-institutional trial. Lipid priming activity in children with SCD Group/Clinical Status Baseline VOC ACS Units are nmol O2−/min; † = p≤0.05 versus Baseline and VOC. SCD 1.8±0.8 1.3±0.1 2.3±0.2† SCD + HU 1.6±0.2 1.4±0.3 no data SCD + EX 1.5±0.2 1.8±0.2 no data

The intestinal alkaline phosphatase gene ( ALPI) encodes a digestive brush-border enzyme, which is highly upregulated during small intestinal epithelial cell differentiation. To identify new putative promoter motifs responsible for the regulation of ALPI expression during differentiation of the enterocytes, we have conducted a computer-assisted cis-element search of the proximal human ALPI promoter sequence. A putative recognition site for the transcription factor hepatocyte nuclear factor (HNF)-4 was predicted at the positions from −94 to −82 in relation to the translational start site. The ability of HNF-4α to stimulate the expression from the ALPI promoter was investigated in the nonintestinal Hela cell line. Cotransfection with an HNF-4α expression vector demonstrated a direct activation of the ALPI promoter through this −94 to −82 element. EMSA showed that HNF-4α from nuclear extracts of differentiated intestinal epithelial cells (Caco-2) bound with high affinity to the predicted HNF-4 binding site. A 521 bp promoter fragment containing the HNF-4 binding site demonstrated a differentiation-dependent increase in promoter activity in Caco-2 cells. The presence of the HNF-4 binding site was necessary for this increase to occur.

Abstract The acute chest syndrome (ACS) is a form of acute lung injury (ALI) unique to sickle cell disease (SCD), and for children &gt; 10 years represents the major cause of morbidity and mortality. Although most ALI is thought to be neutrophil (PMN)-mediated, the role of the PMN in ACS remains unknown. ACS has been linked to increases in plasma secretory phospholipase A2-IIA (sPLA2-IIA) activity within 24 hours of its development (Styles et al Blood87:2573–8, 1996). We hypothesize that sPLA2-IIA cleavage of membrane lipids releases lipophilic compounds that prime PMNs and provoke ACS in patients SCD. After obtaining informed consent, heparinized whole blood was drawn from children with SCD when well, at their annual comprehensive clinic visit, and serially when admitted to the hospital, upon admission and every other day until discharge. Plasma was isolated, divided, and stimulated with buffer or sPLA2 for 30 minutes at 37°C. The lipids were extracted and assayed for their ability to prime fMLP-activation of the PMN oxidase quantitated by the rate of O2− production determined by the SOD-inhibitable reduction of cytochrome c at 550 nm. The data (mean ± the standard error of the mean of lipid priming activity at baseline and during hospitalization, see Table) consists of three groups: patients with SCD: patients with no chronic treatment (SCD), patients treated with daily hydroxyurea (+HU), and patients treated with monthly red cell exchanges (+EX). At baseline, there was significant lipid priming activity in untreated patients (SCD) versus either +HU- or +EX-treated patients. The lipid priming decreased in patients with vaso-occlusive disease (VOD = pain crisis) and became significantly different in the four patients with ACS as comapred to their baseline samples. Moreover, 12 hours prior to developing ACS one hospitalized patient demonstrated an increase in sPLA2-IIA liberated lipid priming activity (1.0– to 1.7–fold). We conclude that both HU and EX therapies appear to diminish baseline sPLA2-IIA release of lipid activity in children with SCD as comapred to the untreated SCD group, during the time period prior to development of ACS, the sPLA2-IIA release of lipid priming activity increased as compared to baseline, and when ACS is diagnosed, sPLA2-IIA release of lipid priming activity is statistically increased as compared to baseline lipid priming. These data demonstrate an association between the sPLA2-IIA release of bioactive lipids and ACS, a relationship seen in other forms of ALI including both TRALI and ARDS. Furthermore, the PMN may play a role in ACS but not in VOD. These data need to be corroborated in a larger study of SCD patients in a multi-institutional trial. Lipid Priming Activity in Plasma from SCD patients Treat./Diagnosis Baseline VOD ACS §= p&lt;.05 vs. HU and EX baseline; †=p&lt;.05 vs SCD baseline. SCD 2.3±0.4§ 1.3±0.1 3.4±0.4† SCD + HU 1.6±0.2 1.4±0.3 No data SCD + EX 1.5±0.2 1.8±0.2 No data

AbstractBackground. Acute intermittent porphyria (AIP) is a hereditary metabolic aberration resulting from a partial defect in the activity of the enzyme porphobilinogen deaminase (PBDG) during the course of haeme synthesis. Diabetic metabolism may attenuate the episodes of porphyria related symptoms.Case report. Our subject (male; age 75) was hospitalized one week after onset of diffuse abdominal pain and constipation and overt type 2 diabetes mellitus (DM). The patient’s long history of alcohol intake with acute alcohol consumption 12 days before admission, in the presence of abdominal pain with spectacular remission after oral administration of 5% glucose solution, accompanied by a 2.5 fold increase of urinary porphobilinogen with normal values for porphyrins and urinary lead, and normal full blood count establishes the diagnosis of AIP.Conclusion We describe a case of AIP probably triggered by acute alcohol consumption, with neurovisceral dominant clinical picture mimicking an acute abdomen. Late disease occurrence as first acute episode at older age accompanied by overt type 2 DM, suggests a latent type of AIP in our patient. The appropriate recognition of latent AIP cases in proband’s offspring prevents unnecessary blind surgery when repeated episodes of unexplained abdominal pain occur.

ABSTRACT The Abi protein family consists of putative membrane-bound metalloproteases. While they are involved in membrane anchoring of proteins in eukaryotes, little is known about their function in prokaryotes. In some known bacteriocin loci, Abi genes have been found downstream of bacteriocin structural genes (e.g., pln locus from Lactobacillus plantarum and sag locus from Streptococcus pyogenes), where they probably are involved in self-immunity. By modifying the profile hidden Markov model used to select Abi proteins in the Pfam protein family database, we show that this family is larger than presently recognized. Using bacteriocin-associated Abi genes as a means to search for novel bacteriocins in sequenced genomes, seven new bacteriocin-like loci were identified in Gram-positive bacteria. One such locus, from Lactobacillus sakei 23K, was selected for further experimental study, and it was confirmed that the bacteriocin-like genes (skkAB) exhibited antimicrobial activity when expressed in a heterologous host and that the associated Abi gene (skkI) conferred immunity against the cognate bacteriocin. Similar investigation of the Abi gene plnI and the Abi-like gene plnL from L. plantarum also confirmed their involvement in immunity to their cognate bacteriocins (PlnEF and PlnJK, respectively). Interestingly, the immunity genes from these three systems conferred a high degree of cross-immunity against each other's bacteriocins, suggesting the recognition of a common receptor. Site-directed mutagenesis demonstrated that the conserved motifs constituting the putative proteolytic active site of the Abi proteins are essential for the immunity function of SkkI, and to our knowledge, this represents a new concept in self-immunity.

ABSTRACT Financial reporting operates in a changing social landscape. One focus of change in the contemporary social landscape is growing recognition of the impact of human activity on the natural environment, a significant part of which derives from economic activity. Evidence exists that financial statement users want environmental accounting information, yet it remains underdeveloped. This underdevelopment becomes notable because it is increasingly clear that long-term economic viability is wholly dependent on ecological sustainability. This study furthers our understanding of financial reporting, accounting standards, and the standard-setting process as institutional practices in the U.S. by exploring whether voices raising these emerging concerns find receptivity in accounting standards setting. Searle's (1995, 1998) work on constructing institutional reality provides the theoretical frame. Results add a layer of empirical analysis to prior accounting research using this frame to critique the openness of discourse in developing financial reporting. The American Institute of Certified Public Accountants (AICPA) received 77 comment letters in consideration of SOP 96-1, “Environmental Remediation Liabilities.” These letters are evaluated for rhetorical tone using quantitative content analysis. Sixteen letters take issue with the narrow scope of the proposed treatment of environmental reporting. These 16 are further analyzed using qualitative content analysis. Comparing rhetorical tone and meaning content of the comment letters reveals active discussion of important environmental reporting issues that go beyond the narrow technical standard adopted. Data Availability: Data used in this study are available by contacting the author.

Abl is a nonreceptor tyrosine kinase and plays an essential role in the modeling and remodeling of F-actin by transducing extracellular signals. Abl and its paralog, Arg, are unique among the tyrosine kinase family in that they contain an unusual extended C-terminal half consisting of multiple functional domains. This structural characteristic may underlie the role of Abl as a mediator of upstream signals to downstream signaling machineries involved in actin dynamics. Indeed, a group of SH3-containing accessory proteins, or adaptor proteins, have been identified that bind to a proline-rich domain of the C-terminal portion of Abl and modulate its kinase activity, substrate recognition, and intracellular localization. Moreover, the existence of signaling cascade and biological outcomes unique to each adaptor protein has been demonstrated. In this paper, we summarize functional roles and mechanisms of adaptor proteins in Abl-regulated actin dynamics, mainly focusing on a family of adaptor proteins, Abi. The mechanism of Abl's activation and downstream signaling mediated by Abi is described in comparison with those by another adaptor protein, Crk.

As one of the four major families of pattern recognition receptors (PRRs), toll like receptors (TLRs)are crucial and important components of the innate immune system. Peroxisome proliferatoractivatedreceptors (PPARs) with three isoforms are transcription factors classified as a subfamilyof nuclear receptor proteins, and are of significant regulatory activity in cellular differentiation,development, metabolism, and tumorigenesis. It is well established that PPARs agonists displayanti-inflammatory effects through inhibition of the nuclear factor-kappa B (NF-κB) pathway, akey regulator of immune and inflammatory responses, in a sense that TLRs signaling pathwaysare mainly toward activation of NF-κB. Through a systematic review of previous studies, weaimed to address and clarify the reciprocal interaction between TLRs and PPARs in hope to findalternative therapeutic approaches for inflammatory diseases. Among the available scientificdatabase, 31 articles were selected for this review. A comprehensive review of this databaseconfirms the presence of a cross-talk between PPARs and TLRs, indicating that not onlyPPARs stimulation may affect the expression level of TLRs via several mechanisms leading tomodulating TLRs activities, but also TLRs have the potential to moderate the expression of PPARs.We, therefore, conclude that, as a key regulator of the innate immune system, the interactionbetween PPARs and TLRs is a potential therapeutic target in disease treatment.

We have previously shown that laminin gamma 1 (laminin B2)-chain mRNA levels increase in response to treatment of rat glomerular epithelial cells (GEC) with the cytokine interleukin-1 beta (IL-1 beta) [C. A. Richardson, K. L. Gordon, W. G. Couser, and K. Bomsztyk. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F273-F278, 1995]. IL-1 beta-induced increase in laminin gamma 1-chain gene expression is likely to be transcriptionally regulated. As the laminin gamma 1-chain gene promoter had not previously been cloned in the rat, we cloned the 5'-flanking region of this gene from a rat genomic library. Like the human and murine laminin gamma 1-chain gene promoters, the rat laminin gamma 1-chain gene fragment spanning from nucleotides -1104 to +109, relative to the start codon, is "GC" rich and lacks TATA or CAAT boxes. This rat laminin gamma 1-chain gene promoter region appears to contain at least two transcription initiation sites, i.e., position -169 and -234. In transient transfections in GEC, the -1104/+35 and -1104/-15 fragments cloned upstream of a luciferase reporter gene had very little constitutive activity and were not IL-1 beta responsive. In sharp contrast, a -1104/-234 fragment exhibited constitutive activity and was IL-1 beta responsive. The -1104/-234 fragment contains motifs that recognize Sp1, BCN-1, and ApoE-B1-AP1 DNA-binding activities in GEC nuclear extracts. Collectively, the results of this study suggest that multiple inducible transcription factors may regulate laminin gamma 1-chain gene promoter activity in GEC.

In the past few years, research efforts have focused on plant exploitation for deriving some valuable compounds. Extraction has been usually performed using petrochemical and volatile organic solvents, but nowadays, increased recognition of environmental pollution has prompted the utilization of green solvents as alternatives. Therefore, the aim of the present study was to exploit deep eutectic solvents (DES) (choline chloride: citric acid and choline chloride: glucose) as solvents for extracting valuable phenolic antioxidants from grapes. Investigation was conducted on ten grape varieties, observing seeds and skin as different matrix. Total polyphenol content (TPC) was determined by Folin-Ciocalteu spectrophotometric microassay. Antioxidant activity was investigated using four different tests and results were combined in a unique Antioxidant Composite Index (ACI) to reveal comprehensive information about this biological activity. Polyphenol compounds were identified and quantified with the aim of HPLC-diode array detector (DAD). Overall results support that DES (particularly choline chloride: citric acid) were comparable to conventional solvent, and in most cases even outperformed acidified aqueous ethanol (concerning extraction efficiency and antioxidant activity). Regardless of varietal distinctions, grape seeds have higher antioxidant capacity compared to grape skin, and such findings are according to their phenol compound concentrations.

As the volume of gambling activity continues to expand in the U.S. the question of exactly what constitutes a gambling transaction for income tax purposes takes on increasing significance for taxpayers as well as tax practitioners. The law requires reporting gambling winnings separately from gambling losses. This separation raises the question of what constitutes a gambling winning which rests in turn on the definition of a gambling transaction. Is it a hand of blackjack or a day at the racetrack, a spin of a roulette wheel or the result from $100 placed in a slot machine, a roll of the dice or the night's poker results? Revenue recognition is not often an issue for individual taxpayers who report their income on a cash basis. The income recognition doctrine of constructive receipt reduces the direct control a cash basis taxpayer can exercise over the timing of the recognition of income. For the increasing number of taxpayers engaging in gambling activities, this doctrine may directly impact the amount of income they are required to recognize not merely because of the gambling income itself (some or all of which may be offset with a deduction for gambling losses) but as a result of this income's impact on adjusted gross income (AGI). While the exact definition of a gambling transaction, and thus the proper recognition of gambling income, is addressed by the I.R.S., it remains a contentious issue. However, when the doctrine of constructive receipt is extended to gambling revenue it clarifies the meaning of a gambling transaction and hence the proper amount of gambling income to be reported by taxpayers.

Factor VIII (FVIII) with a multi-domain structure (A1-a1-A2-a2-B-a3-A3-C1-C2) is a procofactor and precursor for the anti-hemophilic cofactor protein, FVIIIa. Following the intracellular processing within the B domain, secreted FVIII circulates as a heterodimer with variably sized (90K-200K) heavy chain (A1-a1-A2-a2-B) and an 80K light chain (a3-A3-C1-C2). Proteolytic activation of FVIII by thrombin that yields heterotrimeric FVIIIa (A1-a1/A2-a2/A3-C1-C2), the cofactor for intrinsic tenase, involves cleavage of three peptide bonds between Arg372-Ser373, Arg740-Ser741, and Arg1689-Ser1690. Cleavage at Arg740 removes the B-domain, and cleavage at Arg1689 removes the a3-acidic region and releases FVIII from vWF, its carrier protein, and exposes membrane binding sites within the FVIII light chain. Cleavage at Arg372 separates A1-a1 and A2-a2 domains and is implicated in the cofactor-dependent recognition and enhancement in the rate of factor X (FX) activation by intrinsic tenase. Subsequently, the separated A2-a2 domain dissociates spontaneously from the heterotrimeric FVIIIa resulting in the rapid loss of cofactor activity. We speculated that the requirement for cleavage at Arg372 might be obviated by the insertion of an optimized linker sequence between A1-a1 and A2-a2 domains on an uncleavable Gln372 backbone. To investigate this possibility, we prepared cDNA constructs of B-domain deleted FVIII variants; FVIII wild-type (FVIIIWT), FVIII372Q, and FVIII372Q followed by a rigid (Ala-Pro)5 linker sequence (FVIII372Q-AP5). All three FVIII constructs were stably transfected into BHK cells and high expressing clones were selected by one stage aPTT and western blotting of expression media. Selected stable clones were further expanded to collect 15L of expression media over 5-day period, and recombinant FVIII variants were purified using a three-step chromatographic approach. These FVIII variants were studied using SDS-PAGE, western blotting, aPTT assays, thrombin generation assay (TGA) and purified assays to assess kinetics of FX activation and spontaneous loss of cofactor activity. In contrast to FVIIIWT, FVIII372Q and FVIII372Q-AP5 were completely resistant to cleavage at Gln372 by thrombin, yielding bands corresponding to A1-a1-A2-a2 (90K) and A3-C1-C2 (73K). In one stage aPTT assays, FVIII372Q showed prolonged clotting times with specific activity in the range of 200-400 U/mg, while FVIIIWT and FVIII372Q-AP5 displayed comparable clotting times with specific activities ranging between 8000-10000 U/mg and 4500-5500 U/mg, respectively. In TGA initiated with either 0.1 pM tissue factor or 1 pM factor XIa, both FVIIIWT and FVIII372Q-AP5 displayed similar TGA profiles. In steady state kinetic studies of FX activation using limiting concentrations of factor IXa, saturating concentrations of FVIII variants pretreated with thrombin, membranes and increasing concentrations of FX, the cofactor function of thrombin-cleaved FVIII372Q was severely impaired. However, despite lack of cleavage at Gln372 in FVIII372Q-AP5, catalytic efficiency for FX activation by intrinsic tenase assembled by this variant was comparable to that seen with FVIIIaWT. At the physiological concentration of FX, the initial velocity for Xa formation (v/E) for intrinsic tenase assembled with FVIIIa372Q-AP5 was within a factor of 2 of that observed with FVIIIaWT while the rate observed with FVIIIa372Q was &gt;10-fold lower. Following rapid activation with thrombin, loss of cofactor function was significantly slower for FVIIIa372Q-AP5(t1/2 ~ 10 min) compared to FVIIIaWT (t1/2 ~ 2 min). Our findings indicate that the requirement for cleavage at Arg372 for the development of full FVIIIa cofactor function can be overcome by modulating the A1-A2 connector with an optimized linker sequence. Failure to yield an infinitely stable cofactor in the case of FVIIIa372Q-AP5 suggests that cleavage at Arg372 does not solely explain the spontaneous loss of FVIIIa cofactor function. Disclosures Krishnaswamy: Bayer: Research Funding.

Abstract Introduction A previous high-density electroencephalography (EEG) investigation in asymptomatic OSA showed regional deficits in sleep EEG power particularly slow wave activity (SWA) during NREM sleep in the parietal region. It is unclear whether treatment with CPAP can reverse local sleep EEG abnormalities in OSA, and whether any recovery is related to improvement in sleep-dependent memory consolidation. Methods Fifteen male participants (age 50.4±6.5yrs, AHI 51.7±23.5/h) with moderate-severe OSA (AHI&gt;15/h) underwent overnight polysomnography with 256-channel high-density EEG at baseline and following 3 months of CPAP therapy. A word paired associates declarative memory task was administered before and after sleep. After artefact removal, spectral analysis was performed for all channels. Topographical power maps were calculated for standard frequency ranges for NREM sleep (164 channels within a 0.57 radius from the vertex). Maps were compared using both absolute and normalized power (z-scores computed for each subject) and differences between baseline and treatment were determined by statistical nonparametric mapping. Results In 11 CPAP compliant patients (intolerant of CPAP [n=3]/high-density EEG [n=1]), analysis of polysomnographic variables showed that total sleep time did not differ but N1 (baseline vs. treatment: 66.9 vs. 39.5 mins,p=0.008) and N2 (195.0 vs. 150.6 mins,p=0.002) sleep was lower and N3 (89.8 vs. 128.7 mins,p=0.003) was higher after CPAP. Topographic analysis of high-density EEG data revealed a regional increase in SWA (1-4.5Hz) EEG power during N3 sleep in a cluster of electrodes overlying the centro-parietal cortex (cluster mean t-value=2.87,p=0.02). The change in overnight declarative memory consolidation (% recognition) after CPAP was significantly correlated with the change in slow spindle frequency activity in frontal regions (cluster mean r=0.875,p=0.003). Conclusion CPAP treatment may enhance localised deficits in sleep EEG activity in OSA, and specific regional recovery may translate to memory improvements in the short-term. These data also highlight the potential for long-term therapeutic effects on cognitive outcomes in OSA. Support

Purpose – This study analyses the role of social networks and their effects on academics' entrepreneurial intentions (AEI), from an academic cognitive perspective. Specifically, the paper investigates how business (distinguishing between industrial and financial links) and personal social networks, through opportunity-relevant information and support, could influence academics' intentions to start a business venture on the basis of their research knowledge. The paper examines the mediator roles of entrepreneurial attitudes (EA) and self-efficacy on opportunity recognition (SOR) as important psychological variables for academics. In the same context, the paper examines the mediator role of gender. Design/methodology/approach – The hypotheses were tested using structural equation modelling analysis, on a sample population of 500 Spanish academics engaged in commercially oriented fields of research. Findings – The results obtained highlight the positive roles played by business (industrial and financial) networks, both directly in promoting AEI, and indirectly via EA and SOR. The paper finds that male and female academics differ in their perceptions of support from business and financial networks and in their use of these resources in business start-up. Practical implications – An understanding of these issues offers opportunities to shape government interventions to assist academic entrepreneurs embarking on a business venture, or those already active in this respect, increasing their effectiveness in building, utilizing and enhancing the quality of networking activities. Originality/value – The paper explores business networking for academics as a factor promoting entrepreneurship. Furthermore, the paper considers an under-researched area that of female entrepreneurship in what is traditionally considered a male-dominated activity.

ABSTRACT Mediator is a general coactivator complex connecting transcription activators and RNA polymerase II. Recent work has shown that the nuclear receptor-interacting MED1/TRAP220 subunit of Mediator is required for peroxisome proliferator-activated receptor γ (PPARγ)-stimulated adipogenesis of mouse embryonic fibroblasts (MEFs). However, the molecular mechanisms remain undefined. Here, we show an intracellular PPARγ-Mediator interaction that requires the two LXXLL nuclear receptor recognition motifs on MED1/TRAP220 and, furthermore, we show that the intact LXXLL motifs are essential for optimal PPARγ function in a reconstituted cell-free transcription system. Surprisingly, a conserved N-terminal region of MED1/TRAP220 that lacks the LXXLL motifs but gets incorporated into Mediator fully supports PPARγ-stimulated adipogenesis. Moreover, in undifferentiated MEFs, MED1/TRAP220 is dispensable both for PPARγ-mediated target gene activation and for recruitment of Mediator to a PPAR response element on the aP2 target gene promoter. However, PPARγ shows significantly reduced transcriptional activity in cells deficient for a subunit (MED24/TRAP100) important for the integrity of the Mediator complex, indicating a general Mediator requirement for PPARγ function. These results indicate that there is a conditional requirement for MED1/TRAP220 and that a direct interaction between PPARγ and Mediator through MED1/TRAP220 is not essential either for PPARγ-stimulated adipogenesis or for PPARγ target gene expression in cultured fibroblasts. As Mediator is apparently essential for PPARγ transcriptional activity, our data indicate the presence of alternative mechanisms for Mediator recruitment, possibly through intermediate cofactors or other cofactors that are functionally redundant with MED1/TRAP220.

Recognition hyperinsulinemia as the root cause of type 2 diabetes mellitus is becoming more supporters. The overload nutrition cell and insulin resistance is developing as a result of hyperinsulinemia. Insulin resistance is not the only one protection mechanism. Functional system to limited excessive insulin action includes other mechanisms. This review describes the reactions that develop in the tissues in diabetic patients and their relationship with excessive exposure to insulin. Negative feedback mechanism under excessive stimulation of insulin action includes action contrainsular hormones, no β-cell response on increasing the glucose in the extracellular medium, reduction of C-peptide, induction of β-cell apoptosis. The compensation mechanisms includes the restriction of consumption of substances and flow of information, the redirecting excess in the adi-pose tissue, the glycogen synthesis and the activation of kinase-3 synthase glycogen. The conditions GI insulin is able to bind and activate receptors IGF-type 1 to a greater extent than insulin receptors. At diabetes the repro-duction, the growth and the differentiation of cells are accelerated, leading to tumor growth, the accumulation of senescent cells. The depletion and reduction of telomerase activity in diabetes mellitus also have an adaptive value. Contact with receptors undifferentiated cells caused by their high sensitivity and low capacity for insulin resistance, operates referral mechanism power is the same as for obesity. Young cells of functionally active or-gans die, some cells accelerate differentiation and less active peripheral located in hypoxic conditions, may be-come cancerous. The author believes that the growth of tumors after intensive treatment of diabetes is associated with excess insulin action.

Abstract CD56+ NK subsets exhibit differential NK receptors (NKR ) such as NCR profiles including killer-Ig-like receptors (KIR), C-lectin (NKG2) and natural cytoxicity receptors (NCR) involved with tumor target recognition (Farag et al Blood, 2002). NK cell activation and NK mediated cytolysis is induced by several NKRs such as NCR (i.e. NKp44, NKp46) and NKG2 surface receptors like NKG2D (Moretta et al, Curr Opinion in Immunol, 2004). Target cell killing by activated NK cells via the granule-dependent pathway is a common mechanism of NK and CTLs and degranulation is followed by the expression of lysosomal-associated membrane protein-1 [LAMP-1] on the cell surface (Penack et al, Leukemia, 2005). CB is limited by the absence of available donor effector cells (NK, CTL, LAK and NKT cells) for infusion after UCBT (Cairo, et al, Transfusion, 2005). We have demonstrated the ability to EvE CB in short-term culture (48 hrs) with IL-2, IL-7, IL-12 and anti-CD3 (ABCY) cryopreserved, thawed, recryopreserved, rethawed and EvE (CTCTE) CB with significant increase in CD3−/16+/56+ bright/dim subsets expressing KIR3DL1, KIR2DL1/S1, KIR2DL2 and CD94/NKG2a (Ayello/Cairo et al BBMT, 2006). In this study, we compared short-term culture (48 hrs) with prolonged cultures (4 to 10 days) on expansion, expression of NCR, NKG2, KIR and cytolytic ability and mechanisms in CTCTE CB. Rethawed nonadherent CB cells were cultured (2–10 days) in serum-free media alone or with anti-CD3 (50 ng/ml), IL-2 (5 ng/ml), IL-7 (10 ng/ml) and IL-12 (10 ng/ml) [ABCY]. NKR expression (CD94, NKG2D, Nkp44 and KIR2DS4), intracellular perforin, granzyme B activity and LAMP-1 receptor (CD107a) expression were determined by flow cytometry. Cytoxicity was measured by europium release assay and tumor targets used were K562, Daudi, neuroblastoma (SHSY5Y) and AML (Kasumi-1) at a 20:1 E:T ratio. C-lectin activating receptor CD94/NKG2D was increased at day 7 vs 2 following ABCY EvE (41.4±0.43 vs 23.7±2.%, p&lt;0.001). Significant increases were seen in activating KIR2DS4 at day 10 vs 2 in ABCY in both CD3−/16+/56+dim and bright subsets (16.9±0.4 vs 2.1±0.2% and 22.3±0.3 vs 0.9± 0.2%, p&lt;0.001, respectively). In contrast, NCR expression in CD3−/16+/56+dim NKp44 subset was significantly decreased at day 10 vs 2 of EvE CB in ABCY (15.2±0.7 vs 27.2±0.7%, p&lt;0.001). Granzyme B expression was increased from day 2 to 10 (25.8± vs 45.1± 1.7%, p&lt;0.001) yet perforin was decreased in EvE CB in ABCY at day 7 vs 2 (68.3±2.19 vs 84.3±1.3%, p&lt;0.001). CD107a expression was significantly increased at day 7 vs 2 in ABCY EvE CB (12.95±1.47 vs 69.34±2.22%, p&lt;0.001). In addition, significant increases in cytolytic activity was demonstrated at day 7 vs 2 of EvE CB cells in ABCY against tumor targets K562 (71.5±±0.81 vs 53.8±3.9%, p&lt;0.001), Daudi (63.9±0.73 vs 31.8±1.8%, p&lt;0.001), SYSY5Y (76.8±6.5 vs 57.5±3.4%, p&lt;0.05) and Kasumi-1 (56.6.5±0.4 vs 38±1.1%, p&lt;0.001). In summary, CB MNC may be thawed at time of CB transplantation, recryopreserved, rethawed at a later date, EvE and activated for up to 10 days to yield significantly increased cytotolytic activity against NHL, AML and neuroblastoma with increased expression of NK KAR KIR2DS4 and granzyme B, LAMP-1 degranulation (NK activation) but decreased NK C-lection CD94/NKG2D, NCR NKp44 and perforin expression.

Liver cirrhosis yearly causes 1.2 million deaths worldwide, ranking as the 10th leading cause of death in the most developed countries. High susceptibility to infections along with a significant risk for infection-related mortality justifies the description of liver cirrhosis as the world’s most common immunodeficiency syndrome. Liver cirrhosis is an end-stage organic disease hallmarked by a multifaceted immune dysfunction due to deterioration of antimicrobial recognition and elimination mechanisms in macrophages along with an impaired antigen presentation ability in circulating monocytes. Bacterial translocation supports—and is supported by—uncontrolled activation of immune cell responses and/or loss of toll-like receptor (TLR) tolerance, which can turn exaggerated inflammatory responses to systemic inflammation. Lipopolysaccharide (LPS) or endotoxin boosts systemic inflammatory activity through activation of TLR-2- and TLR-4-dependent pathways and facilitate a massive production of cytokines. This, in turn, results into elevated secretion of reactive oxygen species (ROS), which further enhances intestinal hyperpermeability and thus sustains a vicious circle of events widely known as “leaky gut.” Albumin can be of particular benefit in cirrhotic patients with spontaneous bacterial peritonitis and/or hepatorenal syndrome type of acute kidney injury (HRS-AKI) due to anti-inflammatory and antioxidative stress as well as volume-expanding properties and endothelial-stabilizing attributes. However, presence of autoantibodies against albumin in patients with liver cirrhosis has been described. Although previous research suggested that these antibodies should be regarded as naturally occurring antibodies (NOA), the origin of the antialbumin immune response is obscure. High occurrence of NAO/albumin complexes in patients with liver disease might reflect a limited clearance capacity due to bypassing portal circulation. Moreover, high burden of oxidized albumin is associated with less favorable outcome in patients with liver cirrhosis. To date, there is no data available as to whether oxidized forms of albumin result in neoepitopes recognized by the immune system. Nevertheless, it is reasonable to hypothesize that these alterations may have the potential to induce antialbumin immune responses and thus favor systemic inflammation.

Abstract CD56+ NK subsets exhibit differential receptor profiles including killer-Ig-like receptors (KIR), C-lectin (NKG2) and natural cytotoxicity receptors (NCR) involved with tumor target recognition which may play a role in ACI for malignancies (Farag et al Blood, 2002). NK cell activation and NK mediated cytolysis is induced by several triggering receptors such as NCR (i.e. NKp44, NKp46) and NKG2 surface receptors like NKG2D (Moretta, et al, Curr Opinion in Immunol, 2004; Marcenaro et al, Eur J Immunol, 2003). UCB is limited by the absence of available donor effector cells (NK, CTL, LAK and NKT cells) for infusion after transplantation for the treatment of minimal residual resistant hematological relapse and/or PTLD (Barker et al, Blood, 2001; Locatelli, et al Blood,1999). We demonstrated the ability to EvE CB in short term culture (48 hrs) with IL-2, IL-7, IL-12 and anti-CD3 (ABCY) cryopreserved, thawed, recryopreserved, rethawed and ex vivo expanded (CTCTE) with significant increase in CD3−/16+/56+ bright/dim subsets expressing KIR3DL1, KIR2DL1/S1, KIR2DL2 and CD94/NKG2A (Ayello/Cairo et al, BBMT, 25a, 2004). In this study, we compared short-term cultures (48 hrs) with prolonged cultures (4 to 10 days) on expansion, maturation and expression of NCR, NKG2, KIR and cytolytic mechanisms in previously cryopreserved CB that were TCTE. CB was cryopreserved and thawed by the NHLBI/COBLT method. (Kurtzberg/Cairo, Transfuison, 2005). Rethawed nonadherent CB cells were cultured (2–10 days) in serum-free medium alone or with anti-CD3 (50 ng/ml, IL-2 (5 ng/ml), IL-7 (10 ng/ml) and IL-12 (10 ng/ml) (ABCY). NK receptor expression (CD94, NKG2C, NKG2D, NKp44, NKp46, KIR2DS4) and intracellular perforin and granzyme B activity were determined by flow cytometry. NK and LAK cytotoxicity was measured by europium release assay. Significant increases were seen in NK activating KIR2DS4 at day 10 vs 2 in ABCY both in CD3−/16+/56+ dim and bright subsets (16.9±0.4 vs 2.1±0.2% and 22.3±0.3 vs 0.9±0.2%, p&lt;0.001, respectively). C-lectin activating receptor CD94/NKG2D was increased at day 7 vs 2 following ABCY EvE (41.4 ±0.43 vs 23.7±2.0 %, p&lt;0.001). A significant increase was seen in NK (CD3−/16+/56+dim) KIR3DL1 subset at day 10 vs 2 (38.3±2.8 vs 18.9±6.3 7%, p&lt;0.05). In contrast, NCR expression in CD3−/16+/56+ dim NKp44 subset was significantly decreasedat day 10 vs 2 of EvE with ABCY (15.2±0.7 vs 27.2±0.7%, p&lt;0.001). A significant decrease was seen in CD3−/16+/56+ dim NKp46 expression following day 10 vs 2 (8.5±0.2 vs 23.5±1.2 %, p&lt;0.001). Perforin expression demonstrated a significant decrease in ABCY at day 10 vs 2 (55.7±1.8 vs 84.3±1.3%, p&lt;0.001) yet increasing levels of granzyme B from day 2 to 10 (25.8±1.8 vs 45.1±1.7%, p&lt;0.0001). A significant increase in CB NK and LAK cytotoxicity was seen in ABCY on day 10 vs 2 (NK: 71.5 ±1.6 vs 53.8±10.3%, p&lt;0.001; LAK: 63.2±0.24 vs 31.8±1.8%, p&lt;0.001). In summary, CB MNC may be thawed at time of CB transplantation, recryopreserved, rethawed and at a later date EvE and activated for 7–10 days to yield viable NK subsets. EvE in ABCY at 10 days yielded increased expression of NK KAR (CD56+dim and bright) and granzyme B expression but decreased NK C-lectin CD94/NKG2D, NCR NKp46 and NKp48 and perforin expression.

Abstract Abstract 3928 Background: NK cells play a role in reducing relapse in hematological malignancy following AlloSCT (Dunbar et al, Haematologica, 2008). NK cell limitations include lack of tumor recognition and/or limited numbers of viable and functional NK cells (Shereck/Cairo et al, Ped Bld Can, 2007). NK ACI provide safe and effective therapy against tumor relapse; yet NK cells are limited to specific cancer types and not all patients demonstrate optimal response (Ruggieri et al. Science, 2002; Ljunggren et al. Nat Rev Immuno, 2007). To circumvent these limitations, methods to expand and activate PBMNCs with genetically engineered K562 cells expressing membrane bound IL-15 and 41BB ligand (K562-mbIL15-41BBL [modK562]; Imai/Campana et al, Blood, 2005) have shown to significantly increase NK cells in number and maintain heterogeneous KIR expression (Fusaki/Campana et al BJH, 2009). We have shown that CB NK cells can be activated/expanded and exhibit enhanced cytolytic activity when cultured in a cytokines/antibody cocktail (Ayello/Cairo et al, BBMT, 2006; Exp Heme, 2009). Objective: To evaluate CBNK expansion, activation, cytolytic mechanism and function against Burkitt lymphoma (BL) tumor target and its influence on NK cell mediated in-vitro and in-vivo cytotoxicity in NOD-SCID mice following stimulation with modK562 cells (generously supplied by D.Campana, St Jude's Children's Hospital, Memphis, Tx). Methods: Following 100GY irradiation, modK562cells were incubated 1:1 with CBMNCs in RPMI+IL-2 (10IU/ml) for 7 days in 5%CO2, 37°C. NK activation marker (LAMP-1), perforin and granzyme B were determined by flow cytometry. Cytotoxicty was determined via europium assay at 20:1 E:T ratio with Ramos (BL) tumor targets (ATCC). The mammalian expression construct (ffLucZeo-pcDNA (generously supplied by L.Cooper, MD, PhD) was transfected to BL cells using lipofectin and selected by zeocin for stable transfection. Six week old NOD-SCID mice received 5×106 BL cells subcutaneously. Upon engraftment, xenografted NOD-SCID mice were divided in 5 groups: injected with PBS (control), BL only, 5×106 wildtype (WT) K562 expanded (E) CBNK cells, modK562 expanded (E) CB NK cells (5×106) and modK562 expanded (E) CBNK cells (5×107). Ex-vivo ECBNK cells were injected weekly for 5 weeks and xenografted NOD-SCID mice were monitored by volumetric measurement of tumor size (Tomayko/Reynolds, Can Chemother Pharmac, 1989), bioluminescent imaging (Inoue et al Exp Heme, 2007) and survival. The survival distribution for each group was estimated using the Fisher exact test. Results: On Day 0, NK cells (CD56+/3-) population was 3.9±1.3%. After 7 days, modK562 expanded CBNK cells was significantly increased compared to WTK562 and media alone (72±3.9 vs 43±5.9 vs 9±2.4%, p<0.01). This represented a 35-fold or 3374±385% increase of the input NK cell number. This was significantly increased compared to WTK562 (1771±300%, p<0.05). ModK562 ECBNK cells demonstrated increased perforin and granzyme B expression compared to WTK562 (42±1.5 vs 15±0.5%,p<0.001; 22±0.5 vs 11±0.3%,p<0.001, respectively). Cytotoxicity was against BL tumor targets was significantly increased (42±3 vs 18±2%,p<0.01), along with NK activation marker expression, CD107a (p<0.05). At 5 weeks, in-vivo studies demonstrated increased survival of NOD-SCID mice receiving both 5×106 and 5×107 modK562 ECBNK cells when compared to those with no treatment (p=0.05, p=0.0007, respectively). There was no difference in survival when comparing mice that received 5×106 vs 5×107 modK562 ECBNK cells (p=0.0894) at 5 weeks. Tumor volume of mice receiving either dose of modK562 ECBNK cells was significantly less than those receiving WTK562 ECBNK cells (1.92±0.57 and 0.37±0.05 vs 3.41±0.25, p=0.0096 and p=0.0001, respectively). Conclusions: CBMNCs stimulated and expanded with modK562 cells results in significant expansion of CBNK cells with enhanced in-vitro cytotoxicity, significant receptor expression of NK activation marker (LAMP-1), and perforin and granzyme B. Furthermore, modK562 ECBNK cells leads to increased survival and lower tumor burden of NOD-SCID mice xenografted with BL. Future directions include modK562 ECBNK cells to be genetically modified to express chimeric antigen receptor CD20 (MSCV-antiCD20-41BB-CD3 ζ) against CD20+ hematologic malignancies for future studies to evaluate whether targeting enhances in-vitro and in-vivo cytotoxicity. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 499 Introduction: CD56+ NK subsets exhibit differential NK receptors (NKR) such as cytotoxicity profiles including killer-Ig-like receptors (KIR), C-lectin (NKG2) and natural cytotoxicity receptors (NCR) involved with tumor target recognition, which, in part, may play a role in adoptive cellular immunotherapy (ACI) for malignancies (Farag et al Blood, 2002). NK cell activation and NK mediated cytolysis is induced by triggering receptors such as NCR (i.e. NKp46), and NKG2 surface receptors like NKG2D (Moretta et al, Curr Opin in Immunol, 2004, Marcenaro et al, Eur J Immunol, 2003). The major limitations of the use of NK cells in ACI include lack of tumor recognition and/or limited numbers of viable and functionally active NK cells (Shereck/Cairo et al. PBC, 2007). To circumvent these limitations, methods to expand and activate PB NK cells by genetic reengineering have been developed (Imai/Campana et al. Blood, 2005). It has been demonstrated that PB NK cells expanded with modified K562 cells expressing membrane bound IL-15 and 4-1BBL (K562-mb15-41BBL; Imai et al Blood, 2005) are significantly increased in number and maintain heterogeneous KIR expression (Fusaki/Campana et al, BJH, 2009) .We have previously reported the ex-vivo expansion, activation and cytolytic activity of CB NK cells with a cocktail of antibody and cytokines (Ayello/Cairo et al, BBMT, 2006; Ayello/Cairo, Exp Hem, 2009, In Press). Objective: In this study, we compared CB NK expansion and activation following stimulation with genetically engineered K562 cells (K562-mb15-41BBL, generously supplied by D.Campana, St Jude's Children's Hospital, Memphis, TN) with wild-type (WT) K562 cells and NK cell characterization expressing inhibiting and activating KIRs, c-lectin, NCRs and NK cytolytic activation. Methods: Following irradiation with 100Gy, K562-mb15-41BBL or WTK562 were incubated at a 1:1 ratio with fresh CB MNCs at 37C, 5% CO2 for 7 days in RPMI-1640+10IU IL-2. NKR expression (KIR2DS4, NKG2D, NKG2A, CD94, KIR3DL1, KIR2DL2, Nkp46) and LAMP-1 (CD107a) receptor expression and NK cell phenotype (CD56 dim and bright subsets) were determined by flow cytometry. Results: On Day 0, NK cells population was 3.9±1.3%. After 7 days in culture, CB NK cells were significantly increased compared to WTK562 and media alone (72±3.9 vs 43±5.9 vs 9±2.4%, p<0.01). This represented a 35-fold or 3374±385% increase of the input NK cell number. This was significantly increased compared to WTK562 (1771±300%, p<0.05). Concomitantly, there was a significant decrease in CB T cells vs WTK562 or media alone (15±2 vs 36±2 vs 51±7%, p<0.001),respectively. There was a significant increase in CD56bright vs CD56dim populations (67 vs 33%, p<0.01) following stimulation with K562-mb15-41BBL. Also, there was a 10-fold increase in CB NK cells expressing KIR3DL1 following stimulation with K562-mb15-41BBL vs WTK562 (p<0.01) and a 5-fold increase in NK KIR2DS4 expression (p<0.05), respectively. There was a significant increase in the expression of NK activation marker, CD107a, compared to WTK562 (51±0.7 vs 32±1.1,p<0.05). There was no change in CB NK cell expression of the c-lectin receptor, CD94/NKG2A and CD94/NKG2D after stimulation with K562-mb15-41BBL. A standard cryopreserved CB unit (25 ml) contains approximately 750×106 MNC. By using the smaller 5-ml aliquot (20%) of a two-aliquot bag (150×106 MNCs × 3.9%=5.8×106 NK cells), this expansion method would hypothetically yield 200×106 CB NK cells after 7 days stimulation with K562-mb15-41BBL. Conclusion: These results suggest that CB MNC can be ex-vivo expanded with K562-mb15-41BBL resulting in specific expansion of CB NK cells with increased NK KIR expression (KIR2DS4 and KIR3DL1) and NK activation (CD107a), along with a significant decrease in CB T cells. This expansion provides a means to enhance specific CB NK cell expansion for possible use for adoptive cellular immunotherapy in the post UCBT setting Disclosures: No relevant conflicts of interest to declare.

It is a great pleasure and at the same time a challenge to introduce a new journal into the global community, especially when the objective is to publish high quality impactful manuscripts or papers. Although, accounting and finance studies constituted a primary focus for most of the scholars because of our understanding of their values. However, only a few of us spend much time to explore emerging areas. Notwithstanding the challenges, this journal seeks to provide readers throughout the world with technology backed quality peer reviewed scholarly articles on a broad range of established and emergent areas to accounting and finance in particular, and business, economics and social sciences in general. A one on one discussions with distinguished scholars attests to the fact that there is a dire necessity for such a journal in the Indian-Pacific axis. In order to create a niche for IPJAF as the most authoritative journal on accounting and finance, a team of highly valuable or distinguished scholars has agreed to serve on the editorial board. I am privileged and opportune to have Associate Editor-in-Chief, Aidi Ahmi (Universiti Utara Malaysia), and Associate Editors: Muhammad Ali Abdul Hamid (University of Sharjah, UAE), Bamidele Adepoju (Bayero University), Abayomi Ambali Alaka (Institute of Chartered Accountants of Nigeria), and Dorcas Adebola Babatunde (Afe Babalola University of Ado-Ekiti). Our editorial board members are scholars from several countries worldwide that are actively engaged in academic and professional committees, supervising doctoral thesis and doctoral teaching level courses. The Editorial Board is supported by a group of competent and experienced international review panel members from different continents of the world. With this synergy, the journal brings a significant representation of the field of accounting and finance both in established and developing areas. Our existence is anchored on the service and dedication of IPJAF editorial board and the editorial team. This inaugural volume consists of five manuscripts. Shitu and Popoola’s article, An investigation of Socially Sustainable Behaviour of Local Players in the Supply Chain of Shea Butter: A Role Theory Perspective, explores the roles, practices, and behaviour of local supply chain stakeholders (women entrepreneurs) in Shea nut picking and Shea butter processing in Rural Borgu, Nigeria. Also, the research examines the local buying agents (LBA) who serve as the middlemen between the rural women and the exporters of Shea butter. The findings indicate that the present active engagement and practices of these local stakeholders do not align with the principles of the sustainable supply chain. The paper exposes factors such as gender disparity, weak access to financial support, and information asymmetry as major contributors to the present roles, practices, and behaviour of the local actors. Lina and Jingga's article, Factors influencing Tax Avoidance activity: An empirical study from Indonesia Stock Exchange, examines the influence of the firm characteristics to tax avoidance activity in the listed companies in Indonesia. The paper adopts the proxies of firm size, leverage, capital intensity, inventory intensity as the business characteristics and return on asset and market-to-book ratio as control variables. The result of this research reveals that leverage has a positive influence towards tax avoidance activity, while the rest variables have no influence towards tax avoidance activity. Adedeji, Popoola and Ong Tse San's article, National Culture and Sustainability Disclosure Practices: A Literature Review, investigates the extent to which national culture is an explanatory variable for firm’s disclosure choices for sustainable development in the advanced, emerging and developing nations of the world, especially that entities interact in globally knowledge-based economies. The paper identifies that not much work had been done in the area of traits and characteristics in specific national cultural environments and their effects on sustainability disclosures, in particular, social and environmental disclosures. The paper concludes with the recognition of the need to gear up researchers and policy making bodies to encourage advancement of studies on the intellectual capital concept and resource-based value theory to enhance sustainability development globally. Imelda and Alodia's article, The analysis of Altman Model and Ohlson Model in Predicting Financial Distress of Manufacturing companies in the Indonesia Stock Exchange, examines the accuracy of the Altman Model and the Ohlson Model in Bankruptcy Prediction. The results of the paper show that the Ohlson Model and the Logit Analysis are more accurate than the Altman Model and the Multiple Discriminant Analysis in predicting bankruptcy of manufacturing firms in the Indonesian Stock Exchange (BEI) in 2010-2014. The paper reveals benchmark for consideration in determining the financial distress of a company such as the ratio of retained earnings to total assets, earnings before interest and taxes to total assets, market value of equity to total liabilities, sales to total assets, debt ratio, and return on assets, working capital to total assets and net income. Arowolo and Ahmad's article, Quality-differentiated Auditors, Block-holders and Monitoring Mechanisms, seeks to investigate how monitoring mechanisms influence the block-holders in 111 Nigerian non-financial listed companies to resolve the problem of business failures as a result of information asymmetry existing in the relationship of the managements with the shareholders. The study also investigates the mediating effect of the quality-differentiated auditors on the relationship between block-holders and monitoring mechanisms. The findings indicate that the block-holders significantly influence monitoring mechanisms. Also, the results reveal that quality-differentiated auditors positively affect monitoring mechanisms and that it significantly explains the relationship between block-holders and monitoring mechanisms. It is my conviction that in the coming year, the vision of IPJAF to publish high quality manuscripts in the established and emergent areas of accounting and finance from academic and professional researchers will be attained, maintained and appreciated. As you read throughout this inaugural volume of IPJAF, I would like to remind you that the success of our journal depends on your active participation and those of your colleagues and friends through submission of high quality articles for review and publication. I assure our prospective authors, regardless of the acceptance of your manuscripts or not, to enjoy the benefits IPJAF provides about mentoring nature of our review process, which provides high quality, helpful reviews tailored to assist authors in improving their manuscripts. I acknowledge your support as we strive to make IPJAF the most authoritative journal on accounting and finance for the community of academic, professional, industry, society and government. Oluwatoyin Muse Johnson PopoolaEditor-in-Chiefpopoola@omjpalpha.com

This research studies about flouting maxim in The B.F.G movie. The research concerns on finding the flouting maxims in The B.F.G movie. This research employed mainly descriptive qualitative method to support in interpreting and analysing the data. The data of this research were utterances produced by Sophie and BFG as main characters in The B.F.G movie. The context of the research was the dialogues of the movie. The data sources of this research were The B.F.G and its script. Meanwhile, the primary instrument of this research was the researcher ourselves. The data were collected by downloading the movie and the script, watching the movie, and then collecting the data which reflects the phenomena of maxim flouting. The paper examines the use of flouts in different situations and explores in what situations the different characters flout the maxims for any conversation. The results show that there were 10 flouting maxims of quantity (42%); 10 flouting maxims of relevance (42%); 2 flouting maxims of quality (8%); and 2 flouting maxims of manner (8%). Hence the total number of flouting maxims is 24. These results suggest that the use of flouts has to do with their different personalities and communities.Keywords: Cooperative Principle, Grice’s Maxim, Flouting MaximHow to Cite: Ulfah-1, R.A.A.N.U.-1., Afrilia, R-2. (2018). An Analysis of Fluting Maxim in BFG Movie. Project, X (X), XX-XX. INTRODUCTIONCommunication is a medium to convey meaning from one to another. As stated by Yule (2006) that communication involves word recognition and meaning recognition. There could be hidden intention in some utterances. Failing to recognize those intentions may lead to misunderstanding and even a dispute. Nevertheless, listener is not always to be in guilt. Sometimes in communication, the speaker may provide incomplete or unclear utterance hence the listener found difficulties to comprehend. Thus it is claimed that language as a tool for communication serves as an instrument to maintain a good relationship between the speaker and the hearer. Dealing with language and communication, cooperative principle proposed by Grice serves as means to achieve effective communication. It is described that speakers and listeners must give contribution as required by each other so that both of them may come to the same understanding of the meaning they are trying to convey. Grice elaborates four conversational maxims: maxim of relevance, maxim of quantity, maxim of quality, and maxim of manner. During conversation, speakers may break the rule of the maxims. The flouting of the maxims may occur in daily life or in movies. Movies as one of literary works mostly functions to entertain the audience. The flouting maxims in movies may be intentionally created to achieve the purpose of entertaining. The BFG is one fantasy adventure film released in 2016 by Walt Disney. It tells about the journey of two different species, a human (Sophie) and a giant (that Sophie called Big Friendly Giant). Since they are from different group of communities, their communication may run ineffective. This study aims at analyzing the flouting maxims occurred in The BFG movie.The Cooperative Principle Cooperative Principle is the basic principle in pragmatics. The Cooperative Principle is principle of conversation that was proposed by Grice. He called The Cooperative Principle as when we try to talk to be cooperative by elevating. He says, “make your conversational contribution such as is required, at the stage at which it occurs, by the accepted purpose or direction of talk exchange in which you are engaged.” Within this principle, he intended four maxims.(Grundy, 1998) (in Ginarsih, 2014)Grice’s MaximMaxim of RelevanceMaxim of relation: This maxim may seem clear in the first look but as Grice himself mentioned it is very difficult to define it exactly: "Though the maxim itself is terse, its formulation conceals a number of problems that exercise me a good deal: questions about what different kinds and focuses of relevance there may be, how these shift in the course of a talk exchange, how to allow for the fact that subjects of conversations are legitimately changed, and so on. I find the treatment of such questions exceedingly difficult, and I hope to revert to them in later work." Grice ( in Kheirabadi, 2012).Maxim of Quantity Maxim of quantity requires that participants of a conversation give their contribution as is required in terms of the quantity of information. To say beyond the quantity of information needed in the conversation is to break the maxim. In making their contribution to the conventional talk, participants should gauge the amount information that is really sought for and give it as much as is necessary. They should not make their contribution either more informative or less informative. (Seken, n.d.2015)Maxim of QualityMaxim of quality requires conventional participants to say things that are true or things that they believe to be true. That is, they do not say anything than they believe to be false or anything of which they do not have any evidence. In other words, to comply with this maxim, a speaker in a conventional exchange must speak on the basis of facts, or he/she must have factual evidence by which to sufficiently support what he/she says as truth. (Seken, n.d.2015)Maxim of Manner Utterances may conform to the maxims or may disobey them by infringing, opting out, and flouting or violating. The infringement of the maxims is because of the speaker‟s imperfect knowledge of linguistic. When speakers decided to be uncooperative, they opt out of observing the maxims. ( Thomas 1995 in Jafari, 2013) Maxim Flouting Flouting a maxim is the case when a speaker purposefully disobeys a maxim at the level of what is said with the deliberate intention of generating an implicature. In this case, the speaker’s choice not to observe the maxim by the words he/she utters may be related to the some motive (such as politeness, style of speaking, etc.) (Seken, n.d.2015).According to Thomas (1995:64 in Mohammed & Alduais, 2012) flouting a maxim occurs where a participant in a conversation chooses to ignore one or more of the maxims by using a conversational implicature. Ignoring maxims by using conversational implicatures means that the participant adds meaning to the literal meaning of the utterance. He further explains the conversational implicature that is added when flouting is not intended to deceive the recipient of the conversation, but the purpose is to make the recipient look for other meaning. Moreover Black (2006:25 in Mohammed & Alduais, 2012) explains that a speaker who flouts maxims is actually aware of the Cooperative Principles and the maxims. In other words, it is not only about the maxims that are broken down but that the speaker chooses an indirect way to achieve the cooperation of the communication.Types of Flouting Maxim In ( Grice’s theory in Nur & Fatmawati, 2015) there are four types of maxim flouting. They are quantity maxim flouting, quality maxim flouting, relevance maxim flouting, and manner maxim flouting. Quantity Maxim FloutingWhen a speaker flouts the maxims under the category of Quantity, she/he blatantly gives either more or less information than the situation demands.For example: A : The other giants. Are they nice, like you a nice?B : No, I regret to say that the guys would eat you alive bite. My twenty four foot, but not in Giant country, and that's where you are. In Giants country now.In the example above, it is not appropriate, because when A asks the B about another giant, B does not answer according to the question. He give more information that not needed by A.Quality Maxim Flouting Thomas (in Fami 2015:15) said that flout maxim of quality occur when the speaker say something which is blatantly untrue or for which he/she lack adequate evidence.For example:A : Not as it happens to me, it is most terrible speakB : Well, I think you speak beautifullyIn the example above, B say untrue or lie. She do this, because she doesn’t want B sad with his speaking.Relevance Maxim FloutingFlouting of maxim relevance, (Ginarsih 2014, n.d.) said that by changing the subject or by failing the address the topic directly is encountered very frequently. For example:A : You mean of my life. For the rest of my life?B : Hey, do not you cold?In this case B did not answer according to the question, B changes the topic of conversation. Manner Maxim FloutingAccording to (Ginarsih 2014, n.d.) The maxim under the category of manner is exploited by giving ambiguity and obscure expressions, failure to be brief and orderly. It is often trying to exclude a third party, as in this sort of exchange between husband and wife.A : Where are you off to?B : I was thinking of going out to get some of that funny white stuff for somebody.A : OK, but don’t be long – dinner is nearly readyB speaks in an ambiguous way, saying “that funny white stuff” and“somebody”, because he is avoiding saying “ice cream” and “her/his Daugther”, so that his little daughter does not become excited and ask for the ice cream before her meal. Sometimes the speakers play with words to heighten the ambiguity, in order to make a point.Movie(Chandra Yuliasman 2014) Movie is happen based on script, but it reflect to our daily life activity mostly. That is why the researcher interested to use movie as media to increase the researcher understanding about flouting maxim. Movie also affect masses in childhood and youth. Movie is also called a film or motion picture, is a series of still or moving images. Based on the theories above, the researcher chose “The BFG (Big Friendly Giant)” as the object of the research.The B.F.GThe B.F.G is a 2016 American fantasy adventure film directed and produced by Steven Spielberg, written by Melissa Mathison and based on the 1982 novel of the same name by Roald Dahl. In the film, an orphan human girl be friends a benevolent giant, dubbed the "Big Friendly Giant", who takes her to Giant Country, where they attempt to stop the man-eating giants that are invading the human world. The writers chose The B.F.G, because in the film contain about friendship and courage, in that movie also have morality and ethics quotes. Steven Spielberg is known for his quality films, such as Jurrasic Park. He has also received three Oscars, and received a Life Achievement Award from the American Film Institute (AFI). Steven hooked some Hollywood actresses to play in the movie B.F.G, such as: Mark Rylance (B.F.G), Ruby Barnhill (Sophie), Penelope Wilton, Jemani Clement, Rebecca Hall, Rafe Spall, and Bill Hader. Steven Spielberg films this In the premiere of premiere The BFG managed to triumph in the Top 10 Box Office by collecting revenues of USD 31 million. Although not a chance to taste the top of the Box Office but The BFG still loved by his fans, especially for lovers of fantasy and adventure movies.METHODThis research uses a descriptive qualitative method to analyse the flouting maxim in The B.F.G movie directed by Steven Spielberg. According to Holloway (in Nur & Fatmawati, n.d.) qualitative research is a form of social inquiry focusing on the interpretation of experience and the world by people.” Therefore, this research is conducted systematically through the technique of data collecting and data analysis. The data are taken from the script, the writers analysed of flouting maxim of quantity, maxim of quality, maxim of relation, and maxim of manner based on Grice’s theories, being used to choose the most frequently method among them, the writer used percentage category based on Multihajz’s formula, in Selvia (2014) as follows: P = Percentage F = Frequency n = Number of Maxims RESULTS AND DISCUSSIONResultsThere are 24 conversations from 100 conversations that found in The B.F.G Movie between the main characters, Sophie and B.F.G that flouted the Grice’s cooperative principle. They flouted the maxim of quantity, the maxim of quality, the maxim of relation, and the maxim of manner. In the calculation the writers employed percentage technique as described below:Table 1The Classification of Maxim:NoTypes of MaximQuantityPercentage1.The Maxim of Quantity1042 %2. The Maxim of Quality28 %3The Maxim of Relevance1042 %4The Maxim of Manner28 %Total24100 %From the classification above, it could be seen clearly that among four types of maxim in conversation between the main characters, Sophie and B.F.G in “The B.F.G” Movie, the maxim of Quantity and Relevance were the most identifiable types. First is Quantity. There are 10 conversations or cover 42 %. The second was the maxim of Relevance; there are 10 conversations or cover 42 %. The third was maxim of Quality; there are 2 conversations or cover 8 %. The fourth was the maxim of Manner; there are 2 conversations or cover 8 %. Based on the table above, here are the explanations of each maxim that the main character, Sophie and B.F.G flouted in The B.F.G Movie. The maxim of quantitySophie : The other giants. Are they nice, like you a nice?B.F.G : No, I regret to say that the guys would eat you alive bite. My twenty four foot, but not in Giant country, and that's where you are. In Giants country now.Analysis: It is not appropriate, because when Sophie asks the BFG about another giant, the BFG does not answer according to the question. He give more information that not needed by Sophie.Sophie : We can’t have secrets. I'll tell you mine. I sneak around at night too, and that still sometimes theft and lying. So I’m alone at the time. I've never had a best friend, I told you all thatB.F.G : We got over.Analysis: The BFG did not give the right reasons to reply to a statement from Sophie.Sophie : You should not let them treat you like that. You should notB.F.G : Live with nine giant eats beans. They take so I return. Murmur good dreams. It's what I can do, I do something. I do something.Analysis: The BFG ignored Sophie’s suggestion of another giant treating the BFG badly and he changed the subject.Sophie : No I’m not.B.F.G : Yes you here. If you are a human being and human being is a strawberry cream for giants. They are the prey of those giants out there, so you stay in a nice safe place right here. Analysis: BFG answer does not fit with the context of the conversation at that time.B.F.G : Someone called me a big, friendly giant. How should I call you? Sophie : My name is SophieAnalysis: Sophie does not understand about a nickname, so she just answers with her name only "Sophie".B.F.G: So you're an orphan?Sophie: Yes. You took me to an orphanage. You did not know?Analysis: Sophie did not give the right reasons to reply to a statement from B.F.G.B.F.G: I did not know that. Are you happy there?Sophie: No! I hate that. The lady who runs it is incompetent and she’s crazy rules and you get punish a lot.Analysis: In this conversation, Sophie should answer yes or no , because the question is are you happy there ?.Sophie : Being is not be ing .What is that green thing ?B.F.G : Frobscuttel. All giant drink frobscottel.Analysis: BFG answer does not fit with the context of the conversation at that time.Sophie : Where are you going now ?B.F.G : A dreams blow .It's what I do next.Analysis: BFG answer does not fit with the context of the conversation at that time. In this conversation Sophie asks where, it means that ask about place.Sophie : But why did you bring me here? Why did you take me?B.F.G : I had did to take you, because the first thing you, you would do spread the news you actually saw a giant and then there would be a big fuss and all human beans would be looking for the giant dresses all excited, and then I would be locked up in a cage to look at me with all the noisy hypo-fat and crocodiles and giraffes. And then there would be a huge hunt for all the boy giantsAnalysis: The BFG gives too much give reason to Sophie, should the BFG give Sophie a simple and precise reason for the question.The maxim of RelevanceSophie : Then, who are you? What kind of monster are you?B.F.G : You as me wrongAnalysis: BFG does not honestly reply to Shopie that he is a giant kind.Sophie : You mean of my life. For the rest of my life. B.F.G : Hey, do not you cold?Analysis: BFG did not answer according to the questionSophie : What did you work? B.F.G : And now she asks me to tell you very big secrets.Analysis: BFG did not answer according to the questionSophie : Flesh head ,he comes to eat me, my blood will be on your hands. B.F.G : Everything about you going against my better judgment.Analysis: BFG tries to make Shopie calm by diverting the conversationSophie : Look at all the stars! B.F.G : Often when it is clear I hear distant music living of the stars in the skyAnalysis: When Shopie wants to show something, BFG answer it with things that are not appropriate.Sophie: Really? B.F.G : You think I'm kidding, right? Analysis: BFG should simply answer "yes" or "no".Sophie : Are there bad dreams here too? B.F.G : It will a TrogglehumperAnalysis: BFG did not answer the question correctly.Sophie : Make them all happy. BFG, your father and your mother taught you about dreams? B.F.G : The Giants do not have mothers or fathers. Analysis: BFG should simply answer “has” or “has not”.Sophie : What is the Sophie’s dream? B.F.G : A golden Phizzwizard. I had not seen in a while. Analysis: BFG does not explain what dreams Sophie will experience.Sophie : You snapped me.B..F.G : Well, you are right. After all, you're just a little thing. I can’t help thinking what your poor mother and father must be …Analysis: BFG should simply answer "yes" and "no", and not discuss the unnecessaryThe maxim of QualityB.F.G : You do, you really do?Sophie : Simply beautifully.Analysis: In this situation of conversation, Sophie gives untrue respond to B.F.G or she lies, because she didn’t want make B.F.G sad with B.F.G’s sentence.B.F.G : Not as it happens to me, it is most terrible speak.Sophie : Well, I think you speak beautifully.Analysis: In this conversation, Sophie say untrue or lie. She did it, because she didn’t want B.F.G sad with his statement.The maxim of mannerSophie : Blood bottler ? B.F.G : Yes and butcherSophie : The butcher. Please don’t eat me.Analysis: BFG does not explain in detail about Bottler.Sophie : But then I wake up.B.F.G : And you wake up.Sophie : But not here.Analysis: There is no alignment in the conversationDiscussionThe writer found total numbers of flouting maxim that produce by main character in “The B.F.G” movie those were 24 utterances. Then divided into four types of flouting, they were quality which had 10 data or 42%, quantity had 2 data or 8%, relevance had 10 data or 42% and manner had 2 data or 8%. Thus the most frequent category of flouting maxim produce is the main character was maxim of quality and maxim of relevance. It means that in this movie, The BFG tended to conduct his flouted utterance for move the conversations. CONCLUSIONThe aim of this research is to find out the flouting maxim by the main characters in “The B.F.G” movie. The result show the most frequent category of flouting maxim by the main character was quality and relevance. It indicates that based on the maxim of quantity, there are some conversations that giving more or less information. Based on the semantics theory it is wrong, because giving more information than the need is flouting the maxim of quantity. For the maxim of relevance, there are some conversations that are not relevance, it is related with Ginarsih statement relevance maxim flouting by changing the subject or by failing the address the topic directly is encountered very frequently. There are only two flouting maxims of quality and manner was less frequent. It indicates mostly the conversation in The B.F.G movie is cooperative. It is different with the previous study, from Iniyanti, A et.al (2014) they found two flouting maxims, there are: maxim of relation and maxim of manner. And from Al-Qaderi (2015) he found that the maxim of quantity was most frequently flouted.After the research, the researcher took a conclusion that even the famous movie, the flouting maxims are can’t be avoid. ACKNOWLEDGMENTSPlace Acknowledgments, including information on the source of any financial support received for the work being published. Place Acknowledgments, including information on the source of any financial support received for the work being published.

This article discusses the existing software, the main task of which is to extract information from digitized documents. From all the software was selected what is based on neural network technology and deep learning. To extract information from documents, manual work of personal computer operators can be used, which takes a long time and does not exclude the influence of the human factor, as well as digitization of documents with further processing in software based on the principle of subordination of documents to templates and rules, data processing speed and the need to make changes to the settings due to a change in the type of document. The article aims to investigate the existing software for extracting data from digital documents based on neural network technology, and their applicability to Ukrainian-language documents. To do this, a simple set of invoices was created and uploaded to the system. The development of a system for extracting information from digitized Ukrainian-language documents using neural networks will speed up data processing, provide an opportunity for their processing depending on the scope of the user of this software. It is established that at present, there are no systems that can independently determine what data is needed for extraction from Ukrainian-language documents. Existing systems require the creation of software that will act as a cover for the functionality of systems that transmit their information through the REST API. Google Form Parser is considered to be the best system, but it requires a constant connection to the Internet, which can be a serious obstacle to the use of such a product in certain areas of activity.

Reading is an activity person to obtain information from something written. Reading involves recognition of the symbol and the letters that make a language. But there are some people who are lazy to read text in English language which is not a language that is used everyday by Indonesian people. In addition to reading, there are also the most common activities to obtain information that is heard. Hear is a way to gain an understanding of the meaning of the information in the form or sound using auditory senses. Reading activities contributed 10% ability for know information, with listening, knowing information can reach 30%. With conditions like this, then it needs an alternative media that can help treat the condition. The alternative media that can be made is text to speech fo r read text in Indonesia language and English language, for detection language using Ari Borneo Algorithm. These systems are made using Delphi 7 programming language, MBROLA Tools as Indonesia-speaking sound generators and Microsoft Speech API as English sound generator. Through this system, userscan absorb information from listening to the reading o f text by both systems.

Lists and Social MediaLists have long been an ordering mechanism for computer-mediated social interaction. While far from being the first such mechanism, blogrolls offered an opportunity for bloggers to provide a list of their peers; the present generation of social media environments similarly provide lists of friends and followers. Where blogrolls and other earlier lists may have been user-generated, the social media lists of today are more likely to have been produced by the platforms themselves, and are of intrinsic value to the platform providers at least as much as to the users themselves; both Facebook and Twitter have highlighted the importance of their respective “social graphs” (their databases of user connections) as fundamental elements of their fledgling business models. This represents what Mejias describes as “nodocentrism,” which “renders all human interaction in terms of network dynamics (not just any network, but a digital network with a profit-driven infrastructure).”The communicative content of social media spaces is also frequently rendered in the form of lists. Famously, blogs are defined in the first place by their reverse-chronological listing of posts (Walker Rettberg), but the same is true for current social media platforms: Twitter, Facebook, and other social media platforms are inherently centred around an infinite, constantly updated and extended list of posts made by individual users and their connections.The concept of the list implies a certain degree of order, and the orderliness of content lists as provided through the latest generation of centralised social media platforms has also led to the development of more comprehensive and powerful, commercial as well as scholarly, research approaches to the study of social media. Using the example of Twitter, this article discusses the challenges of such “big data” research as it draws on the content lists provided by proprietary social media platforms.Twitter Archives for ResearchTwitter is a particularly useful source of social media data: using the Twitter API (the Application Programming Interface, which provides structured access to communication data in standardised formats) it is possible, with a little effort and sufficient technical resources, for researchers to gather very large archives of public tweets concerned with a particular topic, theme or event. Essentially, the API delivers very long lists of hundreds, thousands, or millions of tweets, and metadata about those tweets; such data can then be sliced, diced and visualised in a wide range of ways, in order to understand the dynamics of social media communication. Such research is frequently oriented around pre-existing research questions, but is typically conducted at unprecedented scale. The projects of media and communication researchers such as Papacharissi and de Fatima Oliveira, Wood and Baughman, or Lotan, et al.—to name just a handful of recent examples—rely fundamentally on Twitter datasets which now routinely comprise millions of tweets and associated metadata, collected according to a wide range of criteria. What is common to all such cases, however, is the need to make new methodological choices in the processing and analysis of such large datasets on mediated social interaction.Our own work is broadly concerned with understanding the role of social media in the contemporary media ecology, with a focus on the formation and dynamics of interest- and issues-based publics. We have mined and analysed large archives of Twitter data to understand contemporary crisis communication (Bruns et al), the role of social media in elections (Burgess and Bruns), and the nature of contemporary audience engagement with television entertainment and news media (Harrington, Highfield, and Bruns). Using a custom installation of the open source Twitter archiving tool yourTwapperkeeper, we capture and archive all the available tweets (and their associated metadata) containing a specified keyword (like “Olympics” or “dubstep”), name (Gillard, Bieber, Obama) or hashtag (#ausvotes, #royalwedding, #qldfloods). In their simplest form, such Twitter archives are commonly stored as delimited (e.g. comma- or tab-separated) text files, with each of the following values in a separate column: text: contents of the tweet itself, in 140 characters or less to_user_id: numerical ID of the tweet recipient (for @replies) from_user: screen name of the tweet sender id: numerical ID of the tweet itself from_user_id: numerical ID of the tweet sender iso_language_code: code (e.g. en, de, fr, ...) of the sender’s default language source: client software used to tweet (e.g. Web, Tweetdeck, ...) profile_image_url: URL of the tweet sender’s profile picture geo_type: format of the sender’s geographical coordinates geo_coordinates_0: first element of the geographical coordinates geo_coordinates_1: second element of the geographical coordinates created_at: tweet timestamp in human-readable format time: tweet timestamp as a numerical Unix timestampIn order to process the data, we typically run a number of our own scripts (written in the programming language Gawk) which manipulate or filter the records in various ways, and apply a series of temporal, qualitative and categorical metrics to the data, enabling us to discern patterns of activity over time, as well as to identify topics and themes, key actors, and the relations among them; in some circumstances we may also undertake further processes of filtering and close textual analysis of the content of the tweets. Network analysis (of the relationships among actors in a discussion; or among key themes) is undertaken using the open source application Gephi. While a detailed methodological discussion is beyond the scope of this article, further details and examples of our methods and tools for data analysis and visualisation, including copies of our Gawk scripts, are available on our comprehensive project website, Mapping Online Publics.In this article, we reflect on the technical, epistemological and political challenges of such uses of large-scale Twitter archives within media and communication studies research, positioning this work in the context of the phenomenon that Lev Manovich has called “big social data.” In doing so, we recognise that our empirical work on Twitter is concerned with a complex research site that is itself shaped by a complex range of human and non-human actors, within a dynamic, indeed volatile media ecology (Fuller), and using data collection and analysis methods that are in themselves deeply embedded in this ecology. “Big Social Data”As Manovich’s term implies, the Big Data paradigm has recently arrived in media, communication and cultural studies—significantly later than it did in the hard sciences, in more traditionally computational branches of social science, and perhaps even in the first wave of digital humanities research (which largely applied computational methods to pre-existing, historical “big data” corpora)—and this shift has been provoked in large part by the dramatic quantitative growth and apparently increased cultural importance of social media—hence, “big social data.” As Manovich puts it: For the first time, we can follow [the] imaginations, opinions, ideas, and feelings of hundreds of millions of people. We can see the images and the videos they create and comment on, monitor the conversations they are engaged in, read their blog posts and tweets, navigate their maps, listen to their track lists, and follow their trajectories in physical space. (Manovich 461) This moment has arrived in media, communication and cultural studies because of the increased scale of social media participation and the textual traces that this participation leaves behind—allowing researchers, equipped with digital tools and methods, to “study social and cultural processes and dynamics in new ways” (Manovich 461). However, and crucially for our purposes in this article, many of these scholarly possibilities would remain latent if it were not for the widespread availability of Open APIs for social software (including social media) platforms. APIs are technical specifications of how one software application should access another, thereby allowing the embedding or cross-publishing of social content across Websites (so that your tweets can appear in your Facebook timeline, for example), or allowing third-party developers to build additional applications on social media platforms (like the Twitter user ranking service Klout), while also allowing platform owners to impose de facto regulation on such third-party uses via the same code. While platform providers do not necessarily have scholarship in mind, the data access affordances of APIs are also available for research purposes. As Manovich notes, until very recently almost all truly “big data” approaches to social media research had been undertaken by computer scientists (464). But as part of a broader “computational turn” in the digital humanities (Berry), and because of the increased availability to non-specialists of data access and analysis tools, media, communication and cultural studies scholars are beginning to catch up. Many of the new, large-scale research projects examining the societal uses and impacts of social media—including our own—which have been initiated by various media, communication, and cultural studies research leaders around the world have begun their work by taking stock of, and often substantially extending through new development, the range of available tools and methods for data analysis. The research infrastructure developed by such projects, therefore, now reflects their own disciplinary backgrounds at least as much as it does the fundamental principles of computer science. In turn, such new and often experimental tools and methods necessarily also provoke new epistemological and methodological challenges. The Twitter API and Twitter ArchivesThe Open API was a key aspect of mid-2000s ideas about the value of the open Web and “Web 2.0” business models (O’Reilly), emphasising the open, cross-platform sharing of content as well as promoting innovation at the margins via third-party application development—and it was in this ideological environment that the microblogging service Twitter launched and experienced rapid growth in popularity among users and developers alike. As José van Dijck cogently argues, however, a complex interplay of technical, economic and social dynamics has seen Twitter shift from a relatively open, ad hoc and user-centred platform toward a more formalised media business: For Twitter, the shift from being primarily a conversational communication tool to being a global, ad-supported followers tool took place in a relatively short time span. This shift did not simply result from the owner’s choice for a distinct business model or from the company’s decision to change hardware features. Instead, the proliferation of Twitter as a tool has been a complex process in which technological adjustments are intricately intertwined with changes in user base, transformations of content and choices for revenue models. (van Dijck 343)The specifications of Twitter’s API, as well as the written guidelines for its use by developers (Twitter, “Developer Rules”) are an excellent example of these “technological adjustments” and the ways they are deeply interwined with Twitter’s search for a viable revenue model. These changes show how the apparent semantic openness or “interpretive flexibility” of the term “platform” allows its meaning to be reshaped over time as the business models of platform owners change (Gillespie).The release of the API was first announced on the Twitter blog in September 2006 (Stone), not long after the service’s launch but after some popular third-party applications (like a mashup of Twitter with Google Maps creating a dynamic display of recently posted tweets around the world) had already been developed. Since then Twitter has seen a flourishing of what the company itself referred to as the “Twitter ecosystem” (Twitter, “Developer Rules”), including third-party developed client software (like Twitterific and TweetDeck), institutional use cases (such as large-scale social media visualisations of the London Riots in The Guardian), and parasitic business models (including social media metrics services like HootSuite and Klout).While the history of Twitter’s API rules and related regulatory instruments (such as its Developer Rules of the Road and Terms of Use) has many twists and turns, there have been two particularly important recent controversies around data access and control. First, the company locked out developers and researchers from direct “firehose” (very high volume) access to the Twitter feed; this was accompanied by a crackdown on free and public Twitter archiving services like 140Kit and the Web version of Twapperkeeper (Sample), and coincided with the establishment of what was at the time a monopoly content licensing arrangement between Twitter and Gnip, a company which charges commercial rates for high-volume API access to tweets (and content from other social media platforms). A second wave of controversy among the developer community occurred in August 2012 in response to Twitter’s release of its latest API rules (Sippey), which introduce further, significant limits to API use and usability in certain circumstances. In essence, the result of these changes to the Twitter API rules, announced without meaningful consultation with the developer community which created the Twitter ecosystem, is a forced rebalancing of development activities: on the one hand, Twitter is explicitly seeking to “limit” (Sippey) the further development of API-based third-party tools which support “consumer engagement activities” (such as end-user clients), in order to boost the use of its own end-user interfaces; on the other hand, it aims to “encourage” the further development of “consumer analytics” and “business analytics” as well as “business engagement” tools. Implicit in these changes is a repositioning of Twitter users (increasingly as content consumers rather than active communicators), but also of commercial and academic researchers investigating the uses of Twitter (as providing a narrow range of existing Twitter “analytics” rather than engaging in a more comprehensive investigation both of how Twitter is used, and of how such uses continue to evolve). The changes represent an attempt by the company to cement a certain, commercially viable and valuable, vision of how Twitter should be used (and analysed), and to prevent or at least delay further evolution beyond this desired stage. Although such attempts to “freeze” development may well be in vain, given the considerable, documented role which the Twitter user base has historically played in exploring new and unforeseen uses of Twitter (Bruns), it undermines scholarly research efforts to examine actual Twitter uses at least temporarily—meaning that researchers are increasingly forced to invest time and resources in finding workarounds for the new restrictions imposed by the Twitter API.Technical, Political, and Epistemological IssuesIn their recent article “Critical Questions for Big Data,” danah boyd and Kate Crawford have drawn our attention to the limitations, politics and ethics of big data approaches in the social sciences more broadly, but also touching on social media as a particularly prevalent site of social datamining. In response, we offer the following complementary points specifically related to data-driven Twitter research relying on archives of tweets gathered using the Twitter API.First, somewhat differently from most digital humanities (where researchers often begin with a large pre-existing textual corpus), in the case of Twitter research we have no access to an original set of texts—we can access only what Twitter’s proprietary and frequently changing API will provide. The tools Twitter researchers use rely on various combinations of parts of the Twitter API—or, more accurately, the various Twitter APIs (particularly the Search and Streaming APIs). As discussed above, of course, in providing an API, Twitter is driven not by scholarly concerns but by an attempt to serve a range of potentially value-generating end-users—particularly those with whom Twitter can create business-to-business relationships, as in their recent exclusive partnership with NBC in covering the 2012 London Olympics.The following section from Twitter’s own developer FAQ highlights the potential conflicts between the business-case usage scenarios under which the APIs are provided and the actual uses to which they are often put by academic researchers or other dataminers:Twitter’s search is optimized to serve relevant tweets to end-users in response to direct, non-recurring queries such as #hashtags, URLs, domains, and keywords. The Search API (which also powers Twitter’s search widget) is an interface to this search engine. Our search service is not meant to be an exhaustive archive of public tweets and not all tweets are indexed or returned. Some results are refined to better combat spam and increase relevance. Due to capacity constraints, the index currently only covers about a week’s worth of tweets. (Twitter, “Frequently Asked Questions”)Because external researchers do not have access to the full, “raw” data, against which we could compare the retrieved archives which we use in our later analyses, and because our data access regimes rely so heavily on Twitter’s APIs—each with its technical quirks and limitations—it is impossible for us to say with any certainty that we are capturing a complete archive or even a “representative” sample (whatever “representative” might mean in a data-driven, textualist paradigm). In other words, the “lists” of tweets delivered to us on the basis of a keyword search are not necessarily complete; and there is no way of knowing how incomplete they are. The total yield of even the most robust capture system (using the Streaming API and not relying only on Search) depends on a number of variables: rate limiting, the filtering and spam-limiting functions of Twitter’s search algorithm, server outages and so on; further, because Twitter prohibits the sharing of data sets it is difficult to compare notes with other research teams.In terms of epistemology, too, the primary reliance on large datasets produces a new mode of scholarship in media, communication and cultural studies: what emerges is a form of data-driven research which tends towards abductive reasoning; in doing so, it highlights tensions between the traditional research questions in discourse or text-based disciplines like media and communication studies, and the assumptions and modes of pattern recognition that are required when working from the “inside out” of a corpus, rather than from the outside in (for an extended discussion of these epistemological issues in the digital humanities more generally, see Dixon).Finally, even the heuristics of our analyses of Twitter datasets are mediated by the API: the datapoints that are hardwired into the data naturally become the most salient, further shaping the type of analysis that can be done. For example, a common process in our research is to use the syntax of tweets to categorise it as one of the following types of activity: original tweets: tweets which are neither @reply nor retweetretweets: tweets which contain RT @user… (or similar) unedited retweets: retweets which start with RT @user… edited retweets: retweets do not start with RT @user…genuine @replies: tweets which contain @user, but are not retweetsURL sharing: tweets which contain URLs(Retweets which are made using the Twitter “retweet button,” resulting in verbatim passing-along without the RT @user syntax or an opportunity to add further comment during the retweet process, form yet another category, which cannot be tracked particularly effectively using the Twitter API.)These categories are driven by the textual and technical markers of specific kinds of interactions that are built into the syntax of Twitter itself (@replies or @mentions, RTs); and specific modes of referentiality (URLs). All of them focus on (and thereby tend to privilege) more informational modes of communication, rather than the ephemeral, affective, or ambiently intimate uses of Twitter that can be illuminated more easily using ethnographic approaches: approaches that can actually focus on the individual user, their social contexts, and the broader cultural context of the traces they leave on Twitter. ConclusionsIn this article we have described and reflected on some of the sociotechnical, political and economic aspects of the lists of tweets—the structured Twitter data upon which our research relies—which may be gathered using the Twitter API. As we have argued elsewhere (Bruns and Burgess)—and, hopefully, have begun to demonstrate in this paper—media and communication studies scholars who are actually engaged in using computational methods are well-positioned to contribute to both the methodological advances we highlight at the beginning of this paper and the political debates around computational methods in the “big social data” moment on which the discussion in the second part of the paper focusses. One pressing issue in the area of methodology is to build on current advances to bring together large-scale datamining approaches with ethnographic and other qualitative approaches, especially including close textual analysis. More broadly, in engaging with the “big social data” moment there is a pressing need for the development of code literacy in media, communication and cultural studies. In the first place, such literacy has important instrumental uses: as Manovich argues, much big data research in the humanities requires costly and time-consuming (and sometimes alienating) partnerships with technical experts (typically, computer scientists), because the free tools available to non-programmers are still limited in utility in comparison to what can be achieved using raw data and original code (Manovich, 472).But code literacy is also a requirement of scholarly rigour in the context of what David Berry calls the “computational turn,” representing a “third wave” of Digital Humanities. Berry suggests code and software might increasingly become in themselves objects of, and not only tools for, research: I suggest that we introduce a humanistic approach to the subject of computer code, paying attention to the wider aspects of code and software, and connecting them to the materiality of this growing digital world. With this in mind, the question of code becomes increasingly important for understanding in the digital humanities, and serves as a condition of possibility for the many new computational forms that mediate our experience of contemporary culture and society. (Berry 17)A first step here lies in developing a more robust working knowledge of the conceptual models and methodological priorities assumed by the workings of both the tools and the sources we use for “big social data” research. Understanding how something like the Twitter API mediates the cultures of use of the platform, as well as reflexively engaging with its mediating role in data-driven Twitter research, promotes a much more materialist critical understanding of the politics of the social media platforms (Gillespie) that are now such powerful actors in the media ecology. ReferencesBerry, David M. “Introduction: Understanding Digital Humanities.” Understanding Digital Humanities. Ed. David M. Berry. 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Ed. David M. Berry. London: Palgrave Macmillan, 2012. 191-209.Fuller, Matthew. Media Ecologies: Materialist Energies in Art and Technoculture. Cambridge, Mass.: MIT P, 2005.Gillespie, Tarleton. “The Politics of ‘Platforms’.” New Media & Society 12.3 (2010): 347-64.Harrington, Stephen, Highfield, Timothy J., & Bruns, Axel (2012) “More than a Backchannel: Twitter and Television.” Ed. José Manuel Noguera. Audience Interactivity and Participation. COST Action ISO906 Transforming Audiences, Transforming Societies, Brussels, Belgium, pp. 13-17. 18 Sept. 2012 http://www.cost-transforming-audiences.eu/system/files/essays-and-interview-essays-18-06-12.pdfLotan, Gilad, Erhardt Graeff, Mike Ananny, Devin Gaffney, Ian Pearce, and danah boyd. “The Arab Spring: The Revolutions Were Tweeted: Information Flows during the 2011 Tunisian and Egyptian Revolutions.” International Journal of Communication 5 (2011): 1375-1405. 18 Sep. 2012 ‹http://ijoc.org/ojs/index.php/ijoc/article/view/1246/613›.Manovich, Lev. “Trending: The Promises and the Challenges of Big Social Data.” Debates in the Digital Humanities. Ed. Matthew K. Gold. Minneapolis: U of Minnesota P, 2012. 460-75.Mejias, Ulises A. “Liberation Technology and the Arab Spring: From Utopia to Atopia and Beyond.” Fibreculture Journal 20 (2012). 18 Sep. 2012 ‹http://twenty.fibreculturejournal.org/2012/06/20/fcj-147-liberation-technology-and-the-arab-spring-from-utopia-to-atopia-and-beyond/›.O’Reilly, Tim. “What is Web 2.0? Design Patterns and Business Models for the Next Generation of Software.” O’Reilly Network 30 Sep. 2005. 18 Sep. 2012 ‹http://www.oreillynet.com/pub/a/oreilly/tim/news/2005/09/30/what-is-web-20.html›.Papacharissi, Zizi, and Maria de Fatima Oliveira. “Affective News and Networked Publics: The Rhythms of News Storytelling on #Egypt.” Journal of Communication 62.2 (2012): 266-82.Sample, Mark. “The End of Twapperkeeper (and What to Do about It).” ProfHacker. The Chronicle of Higher Education 8 Mar. 2011. 18 Sep. 2012 ‹http://chronicle.com/blogs/profhacker/the-end-of-twapperkeeper-and-what-to-do-about-it/31582›.Sippey, Michael. “Changes Coming in Version 1.1 of the Twitter API.” 16 Aug. 2012. Twitter Developers Blog. 18 Sep. 2012 ‹https://dev.Twitter.com/blog/changes-coming-to-Twitter-api›.Stone, Biz. “Introducing the Twitter API.” Twitter Blog 20 Sep. 2006. 18 Sep. 2012 ‹http://blog.Twitter.com/2006/09/introducing-Twitter-api.html›.Twitter. “Developer Rules of the Road.” Twitter Developers Website 17 May 2012. 18 Sep. 2012 ‹https://dev.Twitter.com/terms/api-terms›.Twitter. “Frequently Asked Questions.” 18 Sep. 2012 ‹https://dev.twitter.com/docs/faq›.Van Dijck, José. “Tracing Twitter: The Rise of a Microblogging Platform.” International Journal of Media and Cultural Politics 7.3 (2011): 333-48.Walker Rettberg, Jill. Blogging. Cambridge: Polity, 2008.Wood, Megan M., and Linda Baughman. “Glee Fandom and Twitter: Something New, or More of the Same Old Thing?” Communication Studies 63.3 (2012): 328-44.

ABSTRACTStreptococcus pyogenes(group AStreptococcus[GAS]) causes ~700 million human infections/year, resulting in >500,000 deaths. There is no commercial GAS vaccine available. The GAS surface protein arginine deiminase (ADI) protects mice against a lethal challenge. ADI is an enzyme that converts arginine to citrulline and ammonia. Administration of a GAS vaccine preparation containing wild-type ADI, a protein with inherent enzymatic activity, may present a safety risk. In an approach intended to maximize the vaccine safety of GAS ADI, X-ray crystallography and structural immunogenic epitope mapping were used to inform vaccine design. This study aimed to knock out ADI enzyme activity without disrupting the three-dimensional structure or the recognition of immunogenic epitopes. We determined the crystal structure of ADI at 2.5 Å resolution and used it to select a number of amino acid residues for mutagenesis to alanine (D166, E220, H275, D277, and C401). Each mutant protein displayed abrogated activity, and three of the mutant proteins (those with the D166A, H275A, and D277A mutations) possessed a secondary structure and oligomerization state equivalent to those of the wild type, produced high-titer antisera, and avoided disruption of B-cell epitopes of ADI. In addition, antisera raised against the D166A and D277A mutant proteins bound to the GAS cell surface. The inactivated D166A and D277A mutant ADIs are ideal for inclusion in a GAS vaccine preparation. There is no human ortholog of ADI, and we confirm that despite limited structural similarity in the active-site region to human peptidyl ADI 4 (PAD4), ADI does not functionally mimic PAD4 and antiserum raised against GAS ADI does not recognize human PAD4.IMPORTANCEWe present an example of structural biology informing human vaccine design. We previously showed that the administration of the enzyme arginine deiminase (ADI) to mice protected the mice against infection with multiple GAS serotypes. In this study, we determined the structure of GAS ADI and used this information to improve the vaccine safety of GAS ADI. Catalytically inactive mutant forms of ADI retained structure, recognition by antisera, and immunogenic epitopes, rendering them ideal for inclusion in GAS vaccine preparations. This example of structural biology informing vaccine design may underpin the formulation of a safe and efficacious GAS vaccine.

AbstractThis article reviews possible papyrological evidence for rebel activity in the Fayum during the Great Revolt (206-185 BC). A recently-published archive belonging to two Tanis taricheutai has provided evidence for Fayum rebels. Seven further papyri that might describe rebel activity, but have not been read that way before, complement this picture. These documents shed light on the meaning and recognition of violence and crime in a time of revolt.

Pulmonary macrophages play a critical role in the recognition of pathogens, initiation of host defense via inflammation, clearance of pathogens from the airways, and resolution of inflammation. Recently, we have shown a pivotal role for the nuclear factor of activated T-cell cytoplasmic member 3 (NFATc3) transcription factor in modulating pulmonary macrophage function in LPS-induced acute lung injury (ALI) pathogenesis. Although the NFATc proteins are activated primarily by calcineurin-dependent dephosphorylation, here we show that LPS induces posttranslational modification of NFATc3 by polyADP-ribose polymerase 1 (PARP-1)-mediated polyADP-ribosylation. ADP-ribosylated NFATc3 showed increased binding to iNOS and TNFα promoter DNA, thereby increasing downstream gene expression. Inhibitors of PARP-1 decreased LPS-induced NFATc3 ribosylation, target gene promoter binding, and gene expression. LPS increased NFAT luciferase reporter activity in lung macrophages and lung tissue that was inhibited by pretreatment with PARP-1 inhibitors. More importantly, pretreatment of mice with the PARP-1 inhibitor olaparib markedly decreased LPS-induced cytokines, protein extravasation in bronchoalveolar fluid, lung wet-to-dry ratios, and myeloperoxidase activity. Furthermore, PARP-1 inhibitors decreased NF-кB luciferase reporter activity and LPS-induced ALI in NF-кB reporter mice. Thus, our study demonstrates that inhibiting NFATc3 and NF-кB polyADP-ribosylation with PARP-1 inhibitors prevented LPS-induced ALI pathogenesis.

AbstractRecognition of emotional facial expressions is based on simulation and mirroring processes, and the premotor cortex is supposed to support this simulation mechanism. The role of this prefrontal area in processing emotional faces with different valence (anger, fear, happiness and neutral) was explored taking into account the effect of the lateralization model (more right-side activation for negative emotions; more left-side activation for positive emotions) of face processing and anxiety level (high vs low). High-frequency repetitive transcranial magnetic stimulation (rTMS, 10 Hz) was applied to the left prefrontal area to induce an increased activation response within the left premotor cortex. Twenty-nine subjects, who were divided into two different groups depending on their anxiety level (high/low anxiety; State-Trait-Anxiety Inventory (STAI), were asked to detect emotion / no emotion. Accuracy (AcI) and response times (RTs) were considered in response to the experimental conditions. A general significant increased performance was found in response to positive emotions in the case of left-side stimulation. Moreover, whereas high-anxiety subjects revealed a significant negative-valence bias in absence of stimulation, they showed a more significant AcI increasing and RTs decreasing in response to positive emotions in case of left premotor brain activation. The present results highlight the role of the premotor system for facial expression processing as a function of emotional type, supporting the existence of a valence-specific lateralized system within the prefrontal area. Finally, a sort of “restoring effect” induced by TMS was suggested for high-anxiety subjects.

ABSTRACTOnly one naturally occurring human antibody has been described thus far that is capable of potently neutralizing all five ebolaviruses. Here we present two crystal structures of this rare, pan-ebolavirus neutralizing human antibody in complex with Ebola virus and Bundibugyo virus glycoproteins (GPs), respectively. The structures delineate the key protein and glycan contacts for binding that are conserved across the ebolaviruses, explain the antibody’s unique broad specificity and neutralization activity, and reveal the likely mechanism behind a known escape mutation in the fusion loop region of GP2. We found that the epitope of this antibody, ADI-15878, extends along the hydrophobic paddle of the fusion loop and then dips down into a highly conserved pocket beneath the N-terminal tail of GP2, a mode of recognition unlike any other antibody elicited against Ebola virus, and likely critical for its broad activity. The fold of Bundibugyo virus glycoprotein, not previously visualized, is similar to the fold of Ebola virus GP, and ADI-15878 binds to each virus’s GP with a similar strategy and angle of attack. These findings will be useful in deployment of this antibody as a broad-spectrum therapeutic and in the design of immunogens that elicit the desired broadly neutralizing immune response against all members of the ebolavirus genus and filovirus family.IMPORTANCEThere are five different members of theEbolavirusgenus. Provision of vaccines and treatments able to protect against any of the five ebolaviruses is an important goal of public health. Antibodies are a desired result of vaccines and can be delivered directly as therapeutics. Most antibodies, however, are effective against only one or two, not all, of these pathogens. Only one human antibody has been thus far described to neutralize all five ebolaviruses, antibody ADI-15878. Here we describe the molecular structure of ADI-15878 bound to the relevant target proteins of Ebola virus and Bundibugyo virus. We explain how it achieves its rare breadth of activity and propose strategies to design improved vaccines capable of eliciting more antibodies like ADI-15878.

Pl@ntnet is a citizen observatory that relies on artificial intelligence (AI) technologies to help people identify plants with their smartphones (Joly 2014). Over the past few years, Pl@ntNet has become one of the largest plant biodiversity observatories in the world with several million contributors (Bonnet 2020b). Based on user demands, a set of tools and services following the FAIR (Findable, Accessible, Interoperable, Reusable) principles (Wilkinson 2016) were implemented to allow the development of e-floras. After a short description of the platform (see Joly (2015) and Joly (2016) for details), we present three complementary services dedicated to the customization of e-floras. The general workflow of Pl@ntNet can be divided into three main components. First, the Pl@ntNet mobile Android and iOS apps, dedicated to plant identification, allow both anonymous and authenticated users to take a picture of a plant, and to send it to a server for recognition at the species level. This recognition, which is performed by a convolutional neural network (Affouard 2017), allows the user to get a list of candidate species, each associated with a confidence score. The second component of Pl@ntNet's workflow is the enrichment of the database to improve the observation quality of the data collected. Because of the huge volume of data (over four million observations shared in 2020, Pl@ntNet statistics), this enrichment cannot be done solely by expert botanists. This is why various crowdsourcing mechanisms have been put in place allowing the collaborative curation of the data. The third part of the Pl@ntNet workflow is the exploitation of the database, which is made available for the needs of stakeholders such as researchers. For example, the recent sharing of Pl@ntNet data on GBIF's (Global Biodiversity Information Facility) platform, through two complementary datasets, has increased the benefit to the scientific community (examples are available here). To support the development of customized e-floras, three complementary concepts have been developed: micro-projects, groups, and monitoring work spaces, whose services are detailed below: (a) Micro-projects allow full adaptation of all the interfaces of the Pl@ntNet apps to a species list of interest. This e-flora can be linked to a specific geographical area, which allows it to be automatically selected according to the user's location. When several specific geographical areas overlap for a given geolocation, the smallest one is automatically selected. This adaptation increases the accuracy of the identification, as the number of potential species for a given identification request is reduced to the checklist of the micro-project (e.g., Bonnet (2020a)). Up to now, 12 micro-projects adapted to European, African or Asian contexts are running on the platform. A full description of this service is provided in Bonnet (2020c). The API (Application Programming Interface) for the identification service of each e-flora is available on My-Pl@ntNet. (b) Groups allow any user to create a private or public space on the platform (https://identify.plantnet.org/groups), to permit everyone to aggregate a part or all of their observations in the group. A group is "observation-centered" as opposed to a micro-project, which is species-centered. If the group is public, any authenticated user can join and contribute to it; if it is private, only users validated by the group's moderators can become members. When a group is restricted to a specific geographical zone (such as a school, city, or natural area), only observations found in that area are displayed in the group, contrary the micro-project. As all the group's observations can be downloaded (as tabbed or comma separated values) by any of the group's members, group features can be used to conduct statistical analyses on the data in order to study plant plots, plant phenology or user profiles. These groups are used by people who want to structure the activity of a group of people interested in monitoring the biodiversity of a given area, a taxonomical group, or a type of plant habitat. Over 260 groups have already been created by e.g., professional land managers, educators, and plant enthusiasts. (c) Monitoring work spaces allows a given stakeholder to access all the observations and identification requests of a given species list in a particular area. Micro-projects and Groups only allow exploration of plant observations explicitly shared by the authenticated users. However, Pl@ntNet's database contains hundreds of millions of plant identification requests submitted by anonymous users. Monitoring work spaces was set up to allow access by land managers to this rich and important material. These work spaces provide the maps, the list of plant observations, and identification requests (with a very high confidence score on the species identification), for all the species of interest to a given partner. For example, this service has been mobilized to follow the recent development of an invasive species (i.e., Hakea sericea Schrad. &amp; J.C. Wendl.) in and around a natural reserve on the Mediterranean coast. All of these on-demand e-floras and monitoring services accelerate the use of daily-produced data, and inform land managers and scientists of the changes in the floristic composition of monitoring areas.

Abstract Background Acute kidney injury (AKI) is a serious problem during pregnancy. Once occurred, it causes devastating maternal and fetal outcomes. In developed nations, the trend of pregnancy-related AKI (PRAKI) is on a decline due to the advances in obstetrics care and the legality of abortion. On the contrary, this situation remains a major health problem in the developing countries. Aim of the work in the present study, we determine the incidence, etiology and outcome of PRAKI in a sample of Egyptian patients. Methods Prospective observational study to determine the incidence, etiology and outcome of PRAKI was conducted over a period of one year from January to December 2017 at Ain Shams university obstetrics & gynecology hospital. Patients were enrolled in this study once PRAKI at antepartum as well as postpartum period was diagnosed according to the definition of KDIGO AKI guidelines diagnostic criteria Results During the period of the study a total of 13050 obstetric patients were admitted in Ain Shams university obstetrics & gynecology hospital. In total, 78 patients met the diagnostic criteria of PRAKI representing an incidence of 0.59% (78/13050). Pre-eclampsia & sepsis were the two most common causes of PRAKI, others were dehydration, postpartum hge, antepartum hge, UTI, proteinuria for investigation, SLE activity, DIC, TTP, Acute fatty liver of pregnancy, eclampsia, eclampsia complicated with HELLP syndrome, eclampsia with acute fatty liver of pregnancy, HUS, hyperemesis gravidarum, hypertensive emergency. Fifty five patients (70.5%) received conservative management. Hemodialysis was initiated in twelve patients (15.3%) based on standard indication (azotemia, oliguria volume overload, hyperkalemia and/or metabolic acidosis). Hemodialysis and plasma exchange was used for four patients (5.1%). Plasma exchange was indicated for seven patients. None of the patients received peritoneal dialysis or continuous renal replacement therapy. The ultimate evolution was good in 47 (60%) patients with complete recovery of the kidney function.14 women (17.9%) had an increased serum creatinine level at discharge for follow up at outpatient clinic. 6 patients (7.6%) had kept with advanced renal failure requiring hemodialysis. There were 11 cases of death, mortality rate was 14%. Conclusion AKI during pregnancy poses a challenge for physicians. In view of the multifaceted problems that potentially complicate pregnancy in women with AKI. Fortunately, with ongoing improvements in obstetrical care, multidisciplinary approaches comprising nephrologists, obstetricians and neonatologists maternal and perinatal mortality in this setting are largely avoidable. Therefore early recognition of signs and symptoms, close monitoring in high risk cases, early referral and a multidisciplinary team management could potentially prevent progression to higher stages of PRAKI and reduce morbidity and mortality.

Background Acacia cyanophylla is a medicinal plant of the Fabaceae family that is widely distributed in Australia and Asia, also it has many medicinal properties such as antibacterial and antioxidant activity. Thin layer chromatography (TLC) is wildly used in natural product extract analysis as a finger print. Aim and objective: This study is aimed to conducting a qualitative detection of the active compounds in Acacia cyanophylla, Phlomis syriaca and Scolymus hispanicus plants by thin layer chromatography (TLC) method and studying their antibacterial activity. Methods: the qualitative detection of three plants was conducting using thin layer chromatography (TLC) method. Then, aqueous and ethanolic extracts of the aerial parts of the three plants were extracted using an Ultrasonic bath. The antibacterial activity on E. coli isolates for six extracts was evaluated using minimum inhibitory concentration (MIC) test. The active compounds that may be responsible for the antibacterial effect was isolated by direct bioautograph method. Results: Performing Thin-layer chromatography TLC tests show that the three plant contain flavonoids, saponin, bitter principles and essential oils, and all extracts showed antibacterial activity on E. coli isolates, but the ethanolic extract of Acacia cyanophylla was the most effective as the MIC values ranged from 0.097to 3.125mg/mL. Bioautography showed that Escherichia coli was inhibited by most of the separated flavonoids on the TLC plates where four inhibiting spots appeared in yellow color with Acacia cyanophylla and five spots with Scolymus hispanicus, while only one spot appeared with Phlomis syriaca. Conclusion: Acacia cyanophylla extract has been considered as the best antibacterial properties among the selected plants due to the presence of flavonoids Peer Review History: Received: 19 July 2021; Revised: 7 August; Accepted: 2 September, Available online: 15 September 2021 Academic Editor: Ahmad Najib, Universitas Muslim Indonesia, Makassar, Indonesia, ahmad.najib@umi.ac.id UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Sangeetha Arullappan, Universiti Tunku Abdul Rahman, Malaysia, sangeetha@utar.edu.my Taha A.I. El Bassossy, Medicinal and Aromatic Plants Department, Desert Research Center, Cairo, Egypt, tahachemist2008@gmail.com Similar Articles: EVALUATION OF ANTIBACTERIAL RESISTANCE OF BIOFILM FORMS OF AVIAN SALMONELLA GALLINARUM TO FLUOROQUINOLONES

Cassava Leaves (Manihot esculenta Crantz) is one of the food resources that many people consume as vegetables in some regions. People believe that it has natural antioxidant compounds such as phenolic and flavonoids. Also, it contains HCN elements known as toxic compounds. However, HCN levels can be reduced by dry heating and boiling. Phenolic and flavonoids are not resistant to heating and are easily oxidized. This article aim to assess the effect of temperature to antioxidant activity and the decrease of HCN level of cassava leaves. The pretreatment heating by oven (dry heating) and cooking (boiling heating) greatly affects to the antioxidant activity and the reduction of cyanide acid (HCN) level in cassava leaves. This article may be useful for any one or any researcher to determine pretreatment heating temperature and heating method to process prepare cassava leaves. Peer Review History: Received 6 November 2020; Revised 25 Decembe; Accepted 4 January, Available online 15 January 2021 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Comments of reviewer(s): Average Peer review marks at initial stage: 5.0/10 Average Peer review marks at publication stage: 7.5/10 Reviewer(s) detail: Ahmad Najib, Universitas Muslim Indonesia, Makassar, Indonesia, ahmad.najib@umi.ac.id Dr. Marwa A. A. Fayed, University of Sadat City, Egypt, maafayed@gmail.com Prof. Dr. Ali Gamal Ahmed Al-kaf, Sana'a university, Yemen, alialkaf21@gmail.com Similar Articles: PHYTOCHEMICAL INVESTIGATION AND EVALUATION OF ANTIOXIDANT AND THROMBOLYTIC PROPERTIES OF LEAVE EXTRACTS OF GARDENIA CORONARIA BUCH-HAM PHYTOCHEMICAL SCREENING AND IN VITRO ANTIOXIDANT AND ANTI-DIABETIC POTENTIALS OF PERSEA AMERICANA MILL. (LAURACEAE) FRUIT EXTRACT

Cola nitida has been used in traditional medicine to treat diverse ailments including diarrhea. This study is carried out to investigate the antidiarrheal activity of the ethanol and chloroform seed extract of Cola nitida in Wistar albino rats. The ethanol and chloroform extracts of Cola nitida were evaluated with different doses (100mg/kg, 300mg/kg and 650mg/kg of animal weight) orally for antidiarrheal activity using castor oil induced-diarrhea, gastrointestinal motility test and castor oil-induced gastroenteropooling in Wistar albino rats. The observed activity was compared to standard antidiarrheal drug Lopermaide hydrochloride (2mg/kg) and to distilled water (10ml/kg) which served as the negative control. Cola nitida ethanol extract at 150, 300 and 650mg/kg showed 55.64%, 59.73%, and 71.34% inhibition in gastrointestinal motility respectively. A significant reduction in diarrheal episodes (p<0.0001) was also observed with 650mg/kg of both extracts showing 100% inhibition. A reduction in the volume of fluid in the small intestine was also seen, this was however not significant. The chloroform extract of Cola nitida on the other hand produced a significant reduction in volume and weight of small intestinal content (p<0.05) with 650mg/kg showing a 92.73% inhibition of intestinal fluid accumulation. The ethanol and chloroform extract of Cola nitida showed anti-diarrheal activity in animal model by decreasing the frequency of defecation and by reducing gastrointestinal motility and intraluminal fluid accumulation in the intestine. Peer Review History: UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Name: Prof. Dr. Hüsniye Kayalar Affiliation: Ege University, Turkey E-mail: husniyekayalar@gmail.com Name: Dr. Ali Gamal Ahmed Al-kaf Affiliation: Sana'a university, Yemen E-mail: alialkaf21@gmail.com Comments of reviewer(s):

Aim and objective: The discovery and development of new natural antiviral compounds which exhibit various antiviral activities are required. The aim of this investigation is to assess the potential use of the red seaweed Asparagopsis taxiformis as a new source of anti H5N1 agent. Methods: The seaweed was collected from Marsa Matrouh, Mediterranean Sea, Egypt during spring season, the effects of successive extracts and the pure compounds from the investigated alga on H5N1 virus were performed using plaque reduction assay. In addition, the mechanism of action of promising extract on the virus adsorption and replication was determined. Chromatographic and spectroscopic analyses were used for the identification of chemical structure of active compound(s) isolated from the studied seaweed. Results: The obtained results showed that petroleum ether and water algal extracts exhibited high antiviral activity (>99.9%) and the mode of action of extracts was not correlated with virus replication but with its adsorption process.The isolated pure compound was identified as 6-methyl-Δ22-stigmasterol-2, 3 di acetate and its antiviral activity (for H5N1)was tested. Pure compound showed antiviral activity reached 56% at 100 µg/ml. Conclusion: The obtained results suggests that crude extracts and isolated active compound from A. taxiformis has the capacity to protect people against pandemic H5N1preventing virus adsorption to the human host cells. Recommendation for testing the extracts and pure compounds from the studied seaweed as potential inhibitor of COVID-19. Peer Review History: Received 16 March 2021; Revised 29 March; Accepted 21 April, Available online 15 May 2021 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Prof. Dr. Hassan A.H. Al-Shamahy, Sana'a University, Yemen, shmahe@yemen.net.ye Dr. Wadhah Hassan Ali Edrees, Hajja University, Yemen, edress2020@gmail.com Similar Articles: ANTIDIABETIC AND ANTIHYPERLIPIDEMIC ACTIVITY OF DRACAENA CINNABARI BALF. RESIN ETHANOLIC EXTRACT OF SOQATRA ISLAND IN EXPERIMENTAL ANIMALS ANTIHYPERGLYCEMIC AND ANTI-OXIDANT POTENTIAL OF ETHANOL EXTRACT OF VITEX THYRSIFLORA LEAVES ON DIABETIC RATS

Present work involve study of the toxicity and the antitrypanosomal activity of the hemi syntheses (total of thiosemicarbazones) extracted from the substrates (reagents of thiosemicarbazides) in 1N hydrochloric acid medium from Mitracarpus Scaber harvested in the region of Abomey-calavi. The ethanolic, dichloromethane and hydroethanol extracts (50:50 v/v) yielded the alkaloid extracts with yields of 4.44%, 2.48% and 5.08% respectively leading to three products of hemi-synthesis P1, P2 and P3 whose larval toxicities have respective values LC50: 78.1μg/mL, 95μg/mL, and 48.8 μg/mL whereas the toxicity tests of the alkaloid samples of ethanol, dichloromethane and hydroethanolic E1, E2 and E3 extracted from the evaluation of the same larval toxicity test gave values of 83.41μg/mL 102.51μg/mL and 52.91μg/mL respectively. These results were less toxic than those of semisynthetic products. Acute and sub-acute toxicity in non-pregnant NMRI female mice after oral gavage of P2 product has been shown to be non-toxic. The antitrypanosomal test was carried out according to the Alamar blue method, it revealed that P1 moderately inhibits trypanosome parasites (IC50=18.06 μg/mL) as well as P2 and P3 with a respective IC50 of 17.24 μg/mL and 20, 68 μg/mL while the alkaloid totals had lower antitrypanosomal activity than the hemi-synthesis products. Peer Review History: UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 8.5/10 Reviewer(s) detail: Name: Dr. Gehan Fawzy Abdel Raoof Kandeel Affiliation: Pharmacognosy Department, National Research Centre, Dokki, 12622, Giza, Egypt E-mail: gehankandeel9@yahoo.com Name: Dr. Dalia Kamal Zaffar Ali Affiliation: Modern University for technology and information, Egypt E-mail: dr.moda88@gmail.com Comments of reviewer(s):

Aim and objective: Clerodendrum thomsoniae leaves are used in Cameroon to manage diabetes and its related disorders. The study aimed at investigating the antidiabetic effect of the aqueous extract on diet and dexamethasone induced diabetic rats. Methods: Young mature leaves of C thomsoniae were dried, finely powdered and submitted to aqueous extraction. The dehydrated extract was tested in rats at 3 doses 312.5, 625 and 1250 mg/kg based on the local use of the plant. The effect of the extract on the fasting blood glucose in normoglycemic rats and MACAPOS 1 type diet induced diabetic rats, using respectively glibenclamide and metformin as positive control groups, were investigated. Results: AECT significantly reduced blood glucose levels in normoglycemic rats (p<0.05) two hours after administration, from 83±2 mg/dL to 57.39±1.7 mg/dL with the dose of 1250 mg/kg. given the highest reduction rate of 30.86%. In normoglycemic rats 30 minutes after oral glucose overload, the maximum reduction rate was observed with glibenclamide 5 mg / kg and calculated at 49.90% followed by 36.39%, for the extract at 1250 mg / kg. After 30 days of repeated oral administration, AECT produced a reduction on blood glucose levels (p<0.05) in type 2 diabetic rats. This reduction in blood sugar was much more expressed with the dose of 1250mg/kg (73.52±0.71 mg/dL) followed by metformin 38mg/kg (70.21±0.89 mg/dL) as the normal control with no significant difference (P < 0.05). Conclusion: These results show that the antidiabetic activity of AECT can be explained by insulin stimulating effect, also give support to the traditional use of this plant. Peer Review History: Received 11 May 2021; Revised 17 June; Accepted 27 June, Available online 15 July 2021 Academic Editor: Dr. Asia Selman Abdullah, Al-Razi university, Department of Pharmacy, Yemen, asia_abdullah65@yahoo.com UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Dr. Terhemen Festus Swem, Department of Veterinary Physiology and Biochemistry, College of Veterinary Medicine, Federal University of Agriculture, Makurdi, Benue State, Nigeria, swemfestus422@gmail.com Taha A.I. El Bassossy, Medicinal and Aromatic Plants Department, Desert Research Center, Cairo, Egypt, tahachemist2008@gmail.com Prof. Dr. Ali Gamal Ahmed Al-kaf, Sana'a university, Yemen, alialkaf21@gmail.com Similar Articles: ANTIDIABETIC AND ANTIHYPERLIPIDEMIC ACTIVITY OF DRACAENA CINNABARI BALF. RESIN ETHANOLIC EXTRACT OF SOQATRA ISLAND IN EXPERIMENTAL ANIMALS THE SCOPING REVIEW OF CHINESE AND WESTERN MEDICINE TREATMENT OF DIABETIC FOOT IN ASIA ANTIHYPERGLYCEMIC AND ANTI-OXIDANT POTENTIAL OF ETHANOL EXTRACT OF VITEX THYRSIFLORA LEAVES ON DIABETIC RATS EFFECTS OF EMODIN ON BLOOD GLUCOSE AND BODY WEIGHT IN TYPE 1 DIABETIC RATS

The harvested Mitracarpus Scaber plants are identified in the national herbarium and registered under the number AA. 6252/HLB. During this work, three crude extracts are prepared from three organic solvents, namely dichloromethane; ethanol and hydro ethanol in 50/50 v/v proportion. The respective alkaloid extracts obtained from the corresponding crude extracts served as substrates for the hemi synthesis of thiosemicarbazone totals from thiosemicarbazides. The three hemi-synthesis products obtained were tested on eight (08) strains of germs, namely E. coli ATCC 25922, S. aureus ATCC 25923, E. faecalis ATCC 22921, P. aeruginosa ATCC 27853, C. albicans ATCC 10231, S. typhi, K. pneumoniae and Dermatophilus 146. The ethanolic extract of thiosemicarbazones exhibited the best bioactive activity and was found to be the most selective. By a series of bio guided chromatographies: TLC thin layer chromatography; CPA atmospheric pressure chromatography and medium pressure liquid chromatography. MPLC (medium pressure liquid chromatography), separation on dextran gel: Sephadex® LH20). The use of available spectral data, cross-checked with that of the literature, made it possible to identify and purify three (03) molecules of thiosemicarbazones, making it possible to study the biological activity of their combination. Peer Review History: UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Name: Prof. Dr. Ali Gamal Ahmed Al-kaf Affiliation: Sana'a university, Yemen E-mail: alialkaf21@gmail.com Name: Prof. Dr. Amani S. Awaad Affiliation: College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj. KSA E-mail: amaniawaad@hotmail.com Comments of reviewer(s): Similar Articles: ANTIFUNGAL, CYTOTOXIC AND PHYTOTOXICITY OF AERIAL PART OF RANUNCULUS MURICATUS ANTI-INFLAMMATORY AND ANTI-OXIDANT ACTIVITIES OF METHANOL EXTRACT OF BAPHIA NITIDA

Excessive sun exposure causes the epidermal tissue of the skin to be unable to fight negative effects such as skin disorders ranging from mild dermatitis to skin cancer, so skin protection is needed such as the use of sunscreen, many plants in Indonesia contain phenolic and flavonoid contents that can potentially act as sunscreens. This study aims to determine the chemical content of several plants that have potential as sunscreen. Where this research was conducted through data collection from several scientific research journals. The data collection is done online using Google, Google Scholar. Based on the data obtained from several scientific research journals, it can be stated that some plants have the potential to act as sunscreens, by looking at the content they have, namely phenolic and flavonoids. The ethanol extract of 96% of Sembung Rambat Plants (Mikania micrantha Kunth) with an SPF value of 42.8810 with a total flavanoid content of 1.175%. Peer Review History: Received: 10 September 2020; Revised: 15 October; Accepted: 23 October, Available online: 15 November 2020 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 5.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Ahmad Najib, Department of Pharmacognosy-Phytochemystry Universitas Muslim Indonesia-Indonesia, ahmad.najib@umi.ac.id Dr. Gehan Fawzy Abdel Raoof Kandeel, Pharmacognosy Department, National Research Centre, Dokki, 12622, Giza, Egypt, gehankandeel9@yahoo.com Dr. Mohamed Said Fathy Al-Refaey, University of Sadat City, Menofia, Egypt, mido_ph212@yahoo.com Prof. Dr. Ali Gamal Ahmed Al-kaf, Sana'a university, Yemen, alialkaf21@gmail.com Comments of reviewer(s): Similar Articles: A REVIEW ON MEDICINAL USES OF DIFFERENT PLANTS OF EUPHORBIACEAE FAMILY EXPLORING THE ANTIPARASITIC ACTIVITY OF MEDICINAL PLANTS A STUDY ON DIFFERENT PLANTS OF APOCYNACEAE FAMILY AND THEIR MEDICINAL USES PHYTOCHEMISTRY STUDY OF PLANTS BELONGING TO CAPPARIS