Academic literature on the topic 'CR.pIX'

Seasonal influenza infections have a significant global impact leading to increased health and economic burden. The efficacy of currently available seasonal influenza vaccines targeting polymorphic surface antigens has historically been suboptimal. Cellular immune responses against highly conserved Influenza A virus antigens, such as nucleoprotein (NP) and matrix protein-1 (M1), have previously been shown to be associated with protection from disease, whilst viral-vectored vaccines are an effective strategy to boost cell-mediated immunity. We have previously demonstrated that MVA encoding NP and M1 can induce potent and persistent T cell responses against influenza. In this Phase I study, we evaluated the safety and immunogenicity of MVA-NP+M1, which was newly manufactured on an immortalized cell line, in six healthy adult participants. The vaccine was well-tolerated with only mild to moderate adverse events that resolved spontaneously and were comparable to previous studies with the same vaccine manufactured in chick embryo fibroblasts. A significant increase in vaccine-specific T cell responses was detected seven days after immunization and was directed against both antigens in the vector insert. This small Phase I study supports progression of this vaccine to a Phase IIb study to assess immunogenicity and additional protective efficacy in older adults receiving licensed seasonal influenza vaccines.

AbstractVectored vaccines based on highly attenuated modified vaccinia Ankara (MVA) are reported to be immunogenic, tolerant to pre-existing immunity, and able to accommodate and stably maintain very large transgenes. MVA is usually produced on primary chicken embryo fibroblasts, but production processes based on continuous cell lines emerge as increasingly robust and cost-effective alternatives. An isolate of a hitherto undescribed genotype was recovered by passage of a non-plaque-purified preparation of MVA in a continuous anatine suspension cell line (CR.pIX) in chemically defined medium. The novel isolate (MVA-CR19) replicated to higher infectious titers in the extracellular volume of suspension cultures and induced fewer syncytia in adherent cultures. We now extend previous studies with the investigation of the point mutations in structural genes of MVA-CR19 and describe an additional point mutation in a regulatory gene. We furthermore map and discuss an extensive rearrangement of the left telomer of MVA-CR19 that appears to have occurred by duplication of the right telomer. This event caused deletions and duplications of genes that may modulate immunologic properties of MVA-CR19 as a vaccine vector. Our characterizations also highlight the exceptional genetic stability of plaque-purified MVA: although the phenotype of MVA-CR19 appears to be advantageous for replication, we found that all genetic markers that differentiate wildtype and MVA-CR19 are stably maintained in passages of recombinant viruses based on either wildtype or MVA-CR.

Background: Chromium, an essential trace mineral plays an important role in the metabolism of carbohydrate, fat and proteins. Chromium picolinate (Cr.Pic) is used in alternative medicine to treat chromium deficiency. Though Cr.Pic is increasingly used to treat diabetes and obesity, studies on its safety profile is limited.Methods: Acute toxicity study was conducted by oral administration of Cr.Pic (2000 mg/kg body weight). The animals were maintained another 14 days with once a day observation. For sub-chronic studies, test groups were treated with Cr.Pic 10 mg/kg/day for 90 days. Tests for hepatic and renal function were conducted. Effect of Cr.Pic on behavioural changes and motor co-ordination was done on every week. Histopathological studies were conducted on day 90 at the end of the experiment.Results: Acute toxicity study of Cr.Pic showed no signs of toxicity and mortality. Absence of any behavioural alteration or mortality during the period of 14 days indicates that Cr.Pic has no latent effect. Similar results were obtained with sub-chronic studies suggesting safety of Cr.Pic. Cr.Pic treated groups showed no changes in learning and motor co-ordination compared to the untreated group. No gross histopathological changes were seen in any group indicating safety of Cr.Pic.Conclusions: The present study conferred safety profile of Cr.Pic from normal results obtained in hepatic function, renal function, behavioural and histopathological studies, suggesting its safety.

Abstract Background The initial management of Acute bacterial skin and skin structure infection (ABSSSI) is burdensome. It requires empirical antibiotic therapy that covers both gram-positive and gram-negative bacteria. Vancomycin plus aztreonam are the most commonly used antibiotic combination, nonetheless, they have many limitations which limits their use. Hence, many new single agents with MRSA and gram-negative coverage, oral options, and/or good safety profile have been developed to be a potential alternative such as: ceftaroline, ceftobiprole, tigecycline and the recent FDA approved antibiotic (delafloxacin). In the absence of head-to-head trials comparing these agents, we decided to conduct a network meta-analysis for these therapeutic regimens. Methods A Bayesian network meta-analysis of randomized clinical trials identified in PubMed/Medline and Embase databases was conducted. We performed both fixed and random effect models for clinical cure as the primary outcome of interest. Additionally, rankograms were generated using the surface under the cumulative ranking curve (SUCRA) to obtain the treatment ranking probabilities in relation to their relative effect. Results We identified 10 eligible studies involving 4,914 patients. The indirect comparison demonstrated that delafloxacin showed no difference in terms of clinical cure compared with ceftaroline (OR, 0.82, 95% Cr.I 0.39–1.8), ceftobiprole (OR, 0.79, 95% Cr.I 0.32–1.9), SOC (OR, 1.2, 95% Cr.I 0.62–2.4) and tigecycline (OR, 1.0, 95% Cr.I 0.45–2.2) in the fixed effect analysis, nor in the random-effect analysis (OR, 0.8, 95% Cr.I 0.26–2.2; OR, 0.78, 95% Cr.I 0.2–3.0; OR, 1.2, 95% Cr.I 0.51–3.1; and OR, 0.96, 95% Cr.I 0.30–3.0), respectively. Furthermore, the ranking probabilities in the fixed-effect and random-effect analysis showed that ceftaroline was ranked the first in terms of clinical cure (SUCRA, 40.02%) followed by ceftobiprole (SUCRA, 22.80%), delafloxacin (SUCRA, 16.60%), SOC (SUCRA, 13.80%), and then tigecycline (SUCRA, 6.70%). Conclusion Ceftaroline, ceftbiprole, delafoxacin, SOC and tigecycline are similarly effective. However, delafloxacin provides better convenience. Further comparative studies regarding their safety are needed. Disclosures All authors: No reported disclosures.

The aim of this study was to investigate, through finite element analysis, the impact of different restorative techniques on stress distribution in endodontically-treated maxillary first premolars. A human maxillary first premolar was modeled following the real anatomical dimensions, through a periapical radiography, using the Rhinoceros software, version 4.0SR8. The model was then replicated to compose the groups according to the coronary restorative technique: C (coltosol), GI.C (glass ionomer + coltosol), GI (glass ionomer), CR.GI (conventional resin + glass ionomer), and BR.GI (Bulk Fill resin + glass ionomer). After the models were finished, they were imported as IGES files into ANSYS software, version 17.2. Fixation was defined at the base of the cortical bone and the load was applied with 300 N axially to the buccal and palatal cusps. The results generated were in maximum principal stress (MPS), with the CR.GI and BR.GI groups presenting the lowest values of tension concentration and more homogeneous stress distribution, followed by GI, GI.C and C. All restorative techniques affected the stress distribution in endodontically-treated maxillary first premolars, promoting greater tension in the occlusal third, at the interface with the buccal wall, and in the cervical third. Conventional or Bulk Fill resins associated with a glass ionomer base have a superior biomechanical behavior in relation to coltosol or glass ionomer.

To minimize sample dilution effect on SARS-CoV-2 pool testing, we assessed analytical and diagnostic performance of a new methodology, namely swab pooling. In this method, swabs are pooled at the time of collection, as opposed to pooling of equal volumes from individually collected samples. Paired analysis of pooled and individual samples from 613 patients revealed 94 positive individuals. Having individual testing as reference, no false-positives or false-negatives were observed for swab pooling. In additional 18,922 patients screened with swab pooling (1,344 pools), mean Cq differences between individual and pool samples ranged from 0.1 (Cr.I. -0.98 to 1.17) to 2.09 (Cr.I. 1.24 to 2.94). Overall, 19,535 asymptomatic patients were screened using 4,400 RT-qPCR assays. This corresponds to an increase of 4.4 times in laboratory capacity and a reduction of 77% in required tests. Therefore, swab pooling represents a major alternative for reliable and large-scale screening of SARS-CoV-2 in low prevalence populations.

An investigative officer is the first stake holder of the criminal justice system who is responsible to bring each and every fact of the crime and to bring accused before the court of law. Sec- 328,Cr.P.C. emphasis on the inquiry of unsoundness of mind of an accused that believe to be suffering from any mental illness and a magistrate immediately directs prosecution for the a medical examination. If Magistrate is convinced that the person is of unsound mind and consequently incapable of making his defence, he shall postpone proceedings and referred the accused to the hospital for the treatment. Section- 100 to 105 of Mental Health Care Act, 2017 also laid down procedures to deal with mentally ill people who come in contact with law. However, it is found that investigative officers are either not aware of these criminal procedures or showing negligence towards it. Few cases of insanity were cometo notice by the Hon’ble High Courts where investigative officer’s negligence resulted into miscarriage of judgments by lower courts. In this research article authors discussed few cases where Court has found lacuna’s in investigative process and by setting past judgments aside deliver fresh judgment in the favour of an insane defendant. Researcher also explores the issue of human right violation by the criminal justice system itself. In conclusion some deliberations are made to eliminate such issues from criminal justice system.

The purpose of the present study was to determine whether carnitine was responsible for the increased energy metabolism observed in Sprague-Dawley rats following inclusion of lamb meat in their diet. This was tested by feeding one of the following three diets: a control diet (control) based on a standard formulation (AIN-93G), a carnitine-supplemented control diet (CD) and a lamb meat diet (LD). All diets were isocaloric (15.46 kJ/g DM) and contained 18.3% protein, 7.1% fat and 58.3% carbohydrate. The carnitine concentrations in the control diet, CD and LD were 29, 984 and 953 mg/kg, respectively. The expression of carnitine palmitoyltransferase-I(CPT-I)α and CTP-Iβ genes, Na,K-ATPase activities and the contents of fat, ATP and creatine phosphate (Cr.P) in liver and skeletal muscle tissues were measured on Days 7 and 14. Bodyweights, bodyweight gains and oxygen consumption rates (OCR) of rats were also measured. The rats fed the LD had higher OCR, ATP and Cr.P concentrations, expressions of CPT-I gene, Na,K-ATPase activities, and lower fat contents, bodyweights and bodyweight gains (P < 0.05) than did the control-group rats. However, rats fed the CD were not significantly different from those fed the control diet, except for the higher CPT-Iα expression, ATP concentrations and lower fat contents in liver (P < 0.05). We conclude that carnitine intake from lamb was not the main factor accounting for the significant effects of lamb consumption on energy metabolism. However, it is likely that carnitine intake by consumption of lamb meat in the LD partly contributed to lowering fat contents in liver, compared with the CD and the control diet groups.

Background: Randomized-controlled trials (RCTs) reported a finding on the safety and efficacy of percutaneous patent foramen ovale (PFO) closure to prevent stroke recurrence. It showed that the Amplatzer (AMP) device appears to be superior to medical therapy (MT) in preventing strokes and episodes of atrial fibrillation (AF), than other devices. We performed a network meta-analysis (NMA) to evaluate the closure of PFO in preventing subsequent neurological events while investigating the results obtained by specific devices. Methods: We searched 3 databases (MEDLINE, EMBASE, CENTRAL/CCTR) and identified 6 RCTs until March 2019. We performed an NMA and used pooled ORs. Analyses were done in NetMetaXL1.6-WinBUGS1.4. Results: Six RCTs with 3,560 patients (mean age 45.2–46.2 years) were included in the present NMA. Depending on the device, 4 groups of patients were compared with MT: 1,889 patients undergoing PFO closure were significantly less likely to experience a stroke than 1,671 patients treated with MT (ORs 0.41; 95% Cr.I. 0.27–0.60 with fixed-effects model and ORs 0.22; 95% Cr.I. 0.05–0.70 with random-effects model). The patients with AMP showed a similar risk than those treated with Helex/Cardioform (HLX/CF) or with a group of 11 multiple devices. This suggests the equality between the 2 most currently used devices. When assessing TIA and, for the safety analysis, major bleeding, both models confirm no significant difference between any devices and MT. PFO closure increased the risk of new-onset AF: MT induces AF significantly less than all the devices. In favor of the AMP, there is a reduced number of cases of AF versus MT; however, no device superiority has been established in comparing HLX/CF and other devices in a random effect model. Conclusions: Our NMA provides evidence in favor of PFO closure with all the devices currently in use. We can conclude that these devices are better than MT, but not that 1 device is better than the rest in reducing stroke recurrences and AF episodes in the follow-up.

The article deals with the land categorization with special focus on the definition of category FO­REST in the National Forest Inventory of the Czech Republic (NFI CR). Definitions of land categories used in the first cycle of forest inventory in 2001–2004 are evaluated. The first task is to assess the appropriateness of existing land categorization and definition of category FOREST in terms of suitability of used parameters defining individual categories and their values. Their compatibility with international definitions of category FOREST is also assessed. The second task is, based on data from the first cycle of NFI CR, to calculate the area of category FOREST according to the international definition of European National Forest Inventory Network (ENFIN) and to determine whether the area of category FOREST is the same or varies from the area according to the definition FOREST defined in NFI CR.In the first part there is a list of used land classifications in the Czech Republic and there are also described used international classifications. Land categorization and definitions according ENFIN are presented. Further the parameters are chosen in the national definition of NFI CR, which are compared with analogous parameters defined by ENFIN, indicating differences. Subsequently, the area of category FOREST is calculated according to the parameters of national definition and ENFIN definition. Finally, suggestions are given for the land classification into categories for the second cycle of NFI CR, including the appropriate parameters and their values for the definition of category FOREST. Possible ways of their implementation into the methodology of NFI CR are listed.

Le travail concerne la modélisation du soudage par laser Nd:YAG continu. Le modèle est basé sur la définition de deux sources de chaleur qui permettent de déterminer la géométrie de la zone fondue, paramètre essentiel pour prévoir les caractéristiques des assemblages soudés. La première source de chaleur est le capillaire formé au sein du bain liquide. Sa géométrie est définie à partir de l'équation d'équilibre des pressions et de l'ajustement du coefficient d'absorption équivalent intervenant dans la définition de la loi de dépôt d'énergie. La deuxième source de chaleur est liée a la présence du panache au-dessus du capillaire. Une caractérisation de celui-ci est mise en oeuvre montrant qu'il crée une défocalisation partielle du faisceau laser. Une source de géométrie fixée a priori est utilisée de facon à obtenir une partie supérieure de zone fondue conforme à l'expérience. L'évolution expérimentale des paramètres ajustés est ensuite étudiée. Le coefficient d'absorption équivalent est comparé au coefficient lié aux absorptions de Fresnel. Ce dernier est déterminé expérimentalement à partir de la connaissance de l'inclinaison du capillaire. Les valeurs obtenues différant largement des valeurs proposées par ailleurs, ceci montre la nécessité d'aborder les phénomènes d'absorption à l'intérieur du capillaire d'une facon différente. Quant au dimensionnement de la seconde source de chaleur, il a permis de montrer que la puissance diffusée par le panache est de l'ordre de 50% de la puissance incidente. A partir de ce résultat, il est alors possible de modéliser cette seconde source de façon similaire au capillaire. Finalement une seule source de chaleur, association du capillaire et du cratère peut être prise en compte. Cependant la définition de cette source de chaleur nécessite l'étude théorique de la diffusion du faisceau par le panache et du dépôt réel d'énergie à l'intérieur du capillaire

Continuous cell lines that proliferate in chemically defined and simple media have been highly regarded as suitable alternatives for vaccine production. One such cell line is the AG1.CR.pIX avian cell line developed by PROBIOGEN. This cell line can be cultivated in a fully scalable suspension culture and adapted to grow in chemically defined, calf serum free, medium [1]–[5]. The medium composition and cultivation strategy are important factors for reaching high virus titers. In this project, a series of computational methods was used to simulate the cell’s response to different environments. The study is based on the metabolic model of the central metabolism proposed in [1]. In a first step, Metabolic Flux Analysis (MFA) was used along with measured uptake and secretion fluxes to estimate intracellular flux values. The network and data were found to be consistent. In a second step, Flux Balance Analysis (FBA) was performed to access the cell’s biological objective. The objective that resulted in the best predicted results fit to the experimental data was the minimization of oxidative phosphorylation. Employing this objective, in the next step Flux Variability Analysis (FVA) was used to characterize the flux solution space. Furthermore, various scenarios, where a reaction deletion (elimination of the compound from the media) was simulated, were performed and the flux solution space for each scenario was calculated. Growth restrictions caused by essential and non-essential amino acids were accurately predicted. Fluxes related to the essential amino acids uptake and catabolism, the lipid synthesis and ATP production via TCA were found to be essential to exponential growth. Finally, the data gathered during the previous steps were analyzed using principal component analysis (PCA), in order to assess potential changes in the physiological state of the cell. Three metabolic states were found, which correspond to zero, partial and maximum biomass growth rate. Elimination of non-essential amino acids or pyruvate from the media showed no impact on the cell’s assumed normal metabolic state.

This thesis addresses computer-augmented collaborative work. More precisely, it focuses on co-located collaboration where co-workers get together at the same place, usually a meeting room. We assume co-workers to use both mobile devices (i.e. hand-held devices) and a static device (i.e., interactive table). These devices provide multiple output modalities, such as visual output and sound output. The co-workers are assumed to process digital content (e.g., document, videos etc.). According to both common experience and scientific evidence, co-workers often switch between rather individual, self directed work and tightly shared group work; these working styles are denoted as loose and tight collaboration, respectively. The overarching goal of this thesis is to better support seamless transitions between loose and tight collaboration, denoted as fluid collaboration. In order to support such fluid transitions between the two working styles, we have to reflect and mitigate conflicting requirements for both output modalities. In tight collaboration, co-workers appreciate proximity and equal access to content; both workspaces and content are shared. In loose collaboration, co-workers desire sufficient space of their own and minimal interference of their contents and interaction. It was shown that in conventional settings (e.g., interactive tables), a transition between tight and loose collaboration leads to limited personal workspace and thereby to workspace interference, clutter and other constraints. During collaboration, such interference concerns both visual and sound output. In light of these facts, further research on interactive devices (e.g., interactive tables and mobile devices) is needed to support fluid collaboration with different output modalities. These observations lead to the central research question of this thesis: How to support fluid co-located collaboration using visual and sound content? This thesis explores this question in three main research directions: (1) surface-based interaction, (2) spatial interaction and (3) embodied sound interaction, while (1) and (2) address visual content, (3) focuses on auditory content. In each direction, we conceptualized, implemented, and evaluated a set of device concepts plus corresponding interaction concepts, respectively. The first research direction, Surface-Based Interaction, contributes a novel tabletop, called Permulin, that provides (1) a group view providing a common ground during phases of tight collaboration, (2) private full screen views for each collaborator to scaffold loosely coupled collaboration and (3) interaction and visualization techniques for sharing content in-between these views for coordination and mutual awareness. Results from an exploratory study and from a controlled experiment provide evidence for the following advancements: (1) Permulin supports fluid collaboration by allowing the user to transition fluidly between loose and tight collaboration. (2) Users perceive and use Permulin as both a cooperative and an individual device. Amongst others, this is reflected by participants occupying significantly larger interaction areas on Permulin than on a tabletop system. (3) Permulin provides unique awareness properties: participants were highly aware of each other and of their interactions during tightly coupled collaboration, while being able to unobtrusively perform individual work during loosely coupled collaboration. In the second research direction, Spatial Interaction, we simulate future paper-like display devices and investigate how well-known collaboration and interaction techniques with paper documents can be transferred to the field of video navigation based on such devices. Thereby we contribute a device concept and interaction techniques that allows multiple users to collaboratively process collections of videos on multiple paper-like displays. It enables users to navigate in video collections, create an overview of multiple videos, and structure and organize video contents. The proposed approach, coined as CoPaperVideo, leverages physical arrangement of the devices. Results of two user studies indicate that our spatial interaction concepts allow users to flexibly organize and structure multiple videos in physical space and to easily and seamlessly transition between individual and group work. In addition, the spatial interaction concepts leverage the 3D space for interaction and for mitigating space limitations. The first two research directions contribute novel devices and interaction concepts for visual content. Visual interfaces are particularly suitable for collaboration, because they afford direct manipulation of visual content. However, while current devices support both visual and sound output, there is still a lack of suitable devices and interaction concepts for a collaborative direct manipulation of sound content. Hence, the third research direction, Embodied Sound Interaction, explores novel devices and interaction concepts for direct manipulation of sound for fluid collaboration. First, we contribute interfaces that enable users to control sound individually by means of body-based interaction. The concept focuses on the body part where sound is perceived: a user’s own ear. Second, direct manipulation of sound is supported through spatial control of sound sources. Virtual sound sources are situated in 3D space and physically associated with spatially aware paper-like displays that embed videos. By physically moving these displays, each user can then control - and focus on - multiple sound sources individually or collaboratively. The evaluation supports our hypothesis that our embodied sound interaction concepts provide effective sound support for users during fluid collaboration.