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Vaníková, Kateřina, and Eva Buchtelová. "The physiotherapy in woman after breast surgery." Onkologie 11, no. 4 (October 1, 2017): 205–8. http://dx.doi.org/10.36290/xon.2017.039.
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Russo, Daniela M., Alan Williams, Anne Edwards, Diana M. Posadas, Christine Finnie, Marcelo Dankert, J. Allan Downie, and Angeles Zorreguieta. "Proteins Exported via the PrsD-PrsE Type I Secretion System and the Acidic Exopolysaccharide Are Involved in Biofilm Formation by Rhizobium leguminosarum." Journal of Bacteriology 188, no. 12 (June 15, 2006): 4474–86. http://dx.doi.org/10.1128/jb.00246-06.
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ABSTRACT The type I protein secretion system of Rhizobium leguminosarum bv. viciae encoded by the prsD and prsE genes is responsible for secretion of the exopolysaccharide (EPS)-glycanases PlyA and PlyB. The formation of a ring of biofilm on the surface of the glass in shaken cultures by both the prsD and prsE secretion mutants was greatly affected. Confocal laser scanning microscopy analysis of green-fluorescent-protein-labeled bacteria showed that during growth in minimal medium, R. leguminosarum wild type developed microcolonies, which progress to a characteristic three-dimensional biofilm structure. However, the prsD and prsE secretion mutants were able to form only an immature biofilm structure. A mutant disrupted in the EPS-glycanase plyB gene showed altered timing of biofilm formation, and its structure was atypical. A mutation in an essential gene for EPS synthesis (pssA) or deletion of several other pss genes involved in EPS synthesis completely abolished the ability of R. leguminosarum to develop a biofilm. Extracellular complementation studies of mixed bacterial cultures confirmed the role of the EPS and the modulation of the biofilm structure by the PrsD-PrsE secreted proteins. Protein analysis identified several additional proteins secreted by the PrsD-PrsE secretion system, and N-terminal sequencing revealed peptides homologous to the N termini of proteins from the Rap family (Rhizobium adhering proteins), which could have roles in cellular adhesion in R. leguminosarum. We propose a model for R. leguminosarum in which synthesis of the EPS leads the formation of a biofilm and several PrsD-PrsE secreted proteins are involved in different aspects of biofilm maturation, such as modulation of the EPS length or mediating attachment between bacteria.
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Souza Júnior, Manoel Teixeira, and Dennis Gonsalves. "Sequence similarity between the viral cp gene and the transgene in transgenic papayas." Pesquisa Agropecuária Brasileira 40, no. 5 (May 2005): 479–86. http://dx.doi.org/10.1590/s0100-204x2005000500009.
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The Papaya ringspot virus (PRSV) coat protein transgene present in 'Rainbow' and 'SunUp' papayas disclose high sequence similarity (>89%) to the cp gene from PRSV BR and TH. Despite this, both isolates are able to break down the resistance in 'Rainbow', while only the latter is able to do so in 'SunUp'. The objective of this work was to evaluate the degree of sequence similarity between the cp gene in the challenge isolate and the cp transgene in transgenic papayas resistant to PRSV. The production of a hybrid virus containing the genome backbone of PRSV HA up to the Apa I site in the NIb gene, and downstream from there, the sequence of PRSV TH was undertaken. This hybrid virus, PRSV HA/TH, was obtained and used to challenge 'Rainbow', 'SunUp', and an R2 population derived from line 63-1, all resistant to PRSV HA. PRSV HA/TH broke down the resistance in both papaya varieties and in the 63-1 population, demonstrating that sequence similarity is a major factor in the mechanism of resistance used by transgenic papayas expressing the cp gene. A comparative analysis of the cp gene present in line 55-1 and 63-1-derived transgenic plants and in PRSV HA, BR, and TH was also performed.
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Kusi, Baah Aye. "Financial sector transparency and bank interest margins: do quality of political and financial regulatory institutions matter?" Journal of Financial Regulation and Compliance 29, no. 4 (July 9, 2021): 409–33. http://dx.doi.org/10.1108/jfrc-10-2020-0097.
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Purpose This study aims to examine the effect of private (PRST) and public (PUST) sector-led financial sector transparencies on bank interest margins (BIM) termed as social cost of financial intermediation in different institutional quality setups. Design/methodology/approach This study uses a two-step dynamic generalized method of moments panel data and bootstrapped quantile models with 91 economies between 2004 and 2016. Data is sourced from World Development Indicator and Global Development Finance databases. Findings The results show that under strong and weak political and financial regulatory institutional setups, the reducing effect of PRST on BIM are observed and reported while the full sample reports no significant nexus between PRST and PUST on BIM. Furthermore, under political institutional quality sample, economies with strong corruption control and regulatory quality are able to reinforce the dampening effect of PRST on BIM while under the same political institutional quality sample, economies with weak rule of law are able to heighten the reducing effect of PRST on BIM. Moreover, under financial regulator institutional quality sample, economies with strong overall weighted and unweighted, chief executive officer and policy dependent central banks are able to intensify the diminishing effect of PRST on BIM while under the same financial regulator institutional quality sample, economies with weak limits on lending are able to amplify the reducing effect of PRST on BIM. However, PUST is reported to propel lower levels BIM in the bootstrap models, especially in strong institutional economies. Practical implications These findings imply that policymakers may rely on PRST to reduce BIM, especially under financial regulatory institutional quality. Additionally, economies must be careful on their reliance on PRST because the effectiveness of PRST to tame high BIM is dependent on the strength of political and financial regulatory institutions. Originality/value To the best of the authors’ knowledge, this study presents first time international evidence on the effect of private and public sector-led financial transparency on BIM in strong and weak political and financial regulatory institution economies.
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Rajapakshe, Bhavani N., Nisha S. Kottearachchi, Ravin T. Wickramarachchi, and Thilini Amalka. "MOLECULAR EVALUATION OF POTENTIAL RESISTANCE TO PAPAYA RING SPOT VIRUS IN MOUNTAIN PAPAYA (VASCONCELLEA CUNDINAMARCENSIS)." Pakistan Journal of Phytopathology 29, no. 1 (July 12, 2017): 89. http://dx.doi.org/10.33866/phytopathol.029.01.0357.
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Papaya Ring Spot virus (PRSV) is a devastating viral disease in papaya cultivation in Sri Lanka. It was reported that mountain papaya (Vasconcellea cundinamarcensis) exhibits resistance to PRSV. Therefore, this study was conducted to evaluate the potential resistance to PRSV in mountain papaya to be used in papaya improvement breeding programs. Carica papaya and V. Cundinamarcensis were inoculated with PRSV by mechanical inoculation technique and symptoms were evaluated visually. In order to detect the latent infection, a molecular method was developed. PRSV RNA genome segments were amplified using three sets of primers by RTPCR and an amplicon was sequenced to confirm the identity of PRSV. Functional ability of the cDNA was examined using SAND family protein gene (sand) as the reference gene. According to the results, visual symptoms were not observed in mountain papaya while standard visual symptoms appeared in Carica papaya. Three sets of primers were able to amplify the corresponding amplicons in inoculated Carica papaya and sequencing data confirmed that the amplicon was from PRSV. Negative amplification was observed in mountain papaya from the three sets of primers although sand gene amplification was observed, proving the correct functionality of cDNA. Therefore, it can be concluded that mountain papaya is likely to be resistant to PRSV.
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Lai, Kuo-Pao, Shinichi Yamashita, Spencer Vitkus, Chih-Rong Shyr, Shuyuan Yeh, and Chawnshang Chang. "Suppressed Prostate Epithelial Development with Impaired Branching Morphogenesis in Mice Lacking Stromal Fibromuscular Androgen Receptor." Molecular Endocrinology 26, no. 1 (January 1, 2012): 52–66. http://dx.doi.org/10.1210/me.2011-1189.
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Abstract Using the cre-loxP system, we generated a new mouse model [double stromal androgen receptor knockout (dARKO)] with selectively deleted androgen receptor (AR) in both stromal fibroblasts and smooth muscle cells, and found the size of the anterior prostate (AP) lobes was significantly reduced as compared with those from wild-type littermate controls. The reduction in prostate size of the dARKO mouse was accompanied by impaired branching morphogenesis and partial loss of the infolding glandular structure. Further dissection found decreased proliferation and increased apoptosis of the prostate epithelium in the dARKO mouse AP. These phenotype changes were further confirmed with newly established immortalized prostate stromal cells (PrSC) from wild-type and dARKO mice. Mechanistically, IGF-1, placental growth factor, and secreted phosphoprotein-1 controlled by stromal AR were differentially expressed in PrSC-wt and PrSC-ARKO. Moreover, the conditioned media (CM) from PrSC-wt promoted prostate epithelium growth significantly as compared with CM from PrSC-dARKO. Finally, adding IGF-1/placental growth factor recombinant proteins into PrSC-dARKO CM was able to partially rescue epithelium growth. Together, our data concluded that stromal fibromuscular AR could modulate epithelium growth and maintain cellular homeostasis through identified growth factors.
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Gowrishankar, J., and A. J. Pittard. "Superimposition of TyrR Protein-Mediated Regulation on Osmoresponsive Transcription of Escherichia coli proUIn Vivo." Journal of Bacteriology 180, no. 24 (December 15, 1998): 6743–48. http://dx.doi.org/10.1128/jb.180.24.6743-6748.1998.
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ABSTRACT Osmotic regulation of proU expression in the enterobacteria is achieved, at least in part, by a repression mechanism involving the histone-like nucleoid protein H-NS. By the creation of binding sites for the TyrR regulator protein in the vicinity of the ς70-controlled promoter of proU inEscherichia coli, we were able to demonstrate a superposed TyrR-mediated activation by l-phenylalanine (Phe), as well as repression by l-tyrosine, of proU expression in vivo. Based on the facts that pronounced activation in the presence of Phe was observed even at a low osmolarity and that the affinity of binding of TyrR to its cognate sites on DNA is not affected by Phe, we argue that H-NS-mediated repression of proU at a low osmolarity may not involve a classical silencing mechanism. Our data also suggest the involvement of recruited RNA polymerase in the mechanism of antirepression in E. coli.
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Kalleshwaraswamy, C. M., and N. K. Krishna Kumar. "Transmission Efficiency of Papaya ringspot virus by Three Aphid Species." Phytopathology® 98, no. 5 (May 2008): 541–46. http://dx.doi.org/10.1094/phyto-98-5-0541.
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The transmission efficiency of Papaya ringspot virus (PRSV) by three aphid vectors (i.e., Aphis gossypii, A. craccivora, and Myzus persicae) was studied. Efficiency was measured by single-aphid inoculation, group inoculation (using five aphids), duration of virus retention, and the number of plants following a single acquisition access period (AAP) to which the aphids could successfully transmit the virus. Single-aphid inoculation studies indicated that M. persicae (56%) and A. gossypii (53%) were significantly more efficient in transmitting PRSV than A. craccivora (38%). Further, in the former two species, the time required for initiation of the first probe on the inoculation test plant was significantly shorter compared to A. craccivora. PRSV transmission efficiency was 100% in all three species when a group of five aphids were used per plant. There was a perceptible decline in transmission efficiency as the sequestration period increased, although M. persicae successfully transmitted PRSV after 30 min of sequestration. A simple leaf-disk assay technique was employed for evaluating the transmission efficiency of three species of aphids. The results of leaf-disk assays also indicated that A. gossypii (48%) and M. persicae (56%) were more efficient PRSV vectors than A. craccivora. Using leaf-disk assays, the ability of individual aphids to inoculate PRSV serially to a number of plants was studied. Following a single AAP on an infected leaf, M. persicae was more efficient than the other two species with 52.5% transmission after the first inoculation access period (IAP). However, its inoculation efficiency significantly decreased with the second and subsequent IAPs. A. gossypii was able to transmit PRSV sequentially up to four successive leaf disks, but with significantly declining efficiency. Since A. gossypii is reported to be the numerically dominant vector in south India in addition to being a more efficient vector capable of inoculating PRSV to multiple plants, it should be the target vector for control strategies.
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Belangero, Sintia, Gabrielle Navarro, Lais Fonseca, Marcos Leite Santoro, Adrielle Oliveira, Leticia Spindola, Pedro Pan, Rodrigo Bressan, and Ary Gadelha. "S174. POLYENVIRONMENTAL AND POLYGENIC RISK SCORES AND THE EMERGENCE OF PSYCHOTIC EXPERIENCES IN CHILDREN AND ADOLESCENTS." Schizophrenia Bulletin 46, Supplement_1 (April 2020): S103—S104. http://dx.doi.org/10.1093/schbul/sbaa031.240.
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Abstract Background Psychotic experiences (PE) include subliminal hallucinations and delusions without the characteristic functional impairment that constitutes a psychotic disorder. PE are prevalent during childhood and adolescence and studies show a clear link with higher risk to clinical psychosis and schizophrenia. The persistence and accumulation of psychosocial problems are also well established risk factors, but how they interplay with genetic risk is still unclear, especially during developmental stages. Polygenic risk score to schizophrenia (PRS-SZ) and the polyenviromic risk score (PERS) are two validated measures created to assess the contribution of each factor on the development of such psychopathology. Our aim was to verify if PRS and PERS jointly are able to predict psychotic experiences in a cohort of children and adolescents, considering two time-points. Methods We analyzed data from the High Risk Cohort (HRC) for Psychiatric Disorders, composed of 2511 children and adolescents from São Paulo and Porto Alegre. PRS-SZ was calculated using summary statistics from the PGC and corrected for the ten first principal components (PC) of the GWAS. In order to calculate the PERS, we used data corresponding to the nine variables that are consider on the score, being respectively, winter or spring birth, urbanicity, cannabis use, advanced paternal age, obstetric and perinatal complications, physical and sexual abuse, neglect and paternal death, therefore if the person is exposed to one or more enviromic factor the odds ratio corresponding to that factor are added up and divided by all factors considered on the calculation, generating the final score. PE was assessed through the Community Assessment of Psychotic Experiences (CAPE) and a latent variable was generated through confirmatory factor analysis producing a good model fit. The prediction model was performed using different linear regressions where the clinical outcome was the CAPE score and PRS and PERS as independent variables. We performed Spearman’s correlations in order to observe possible correlation between our variables. Results Our sample varied from 9 to 18 years old (Mean: 13.49, SD: 1.9, 53.9% male) and a total of 1704 individuals provided available CAPE scores, PRS and PERS. When Spearman’s correlations were performed, we observed a non-significant weak positive correlation between PERS x CAPE (R2 = 0.0118, p = 0.623) and between PRS x CAPE (R2 = 0.0292, p = 0.228) and a non-significant negative correlation between PERS x PRS (R2 = -0.03051, p = 0.207). Lastly, we perform a multiple linear regression and used in the model the ten first PC as covariables and, we observed that with an increase in one unit in the PRS, the model explain positively about 8% of the PE variance (R2 = 0.007986 (F(12;1691) = 2.143, p = 0.01225). When we used the PRS already adjusted by ten first PC in the model, this significance is lost (R2=0.0008381 F(2);1701, p=0.1804 (PC2 and PC8 explaining the most of variance). Discussion Previous studies have shown a lack of significant association between PRS-SZ and PE for youth samples. Our results are in line with such results, but also depict a trend direction for those variables. Although all correlations were non-significant statically, they show us their direction as discussed below. The higher PERS, higher the psychotic experience, suggesting known environment risk factors for psychosis play a role in the report of PE as well. The higher PRS, the higher psychotic experience also. On the other hand, we found a negative correlation between PERS and PRS. In addition, PERS and PRS jointly were not able to predict psychotic experience. Although non-significant, our results may shed light on knowledge of disease.
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Wu, Di, Longfei Wu, Jian Chen, Mitchell Huber, Xiaoduo He, Shengli Li, Yuchuan Ding, and Xunming Ji. "Primate Version of Modified Rankin Scale for Classifying Dysfunction in Rhesus Monkeys." Stroke 51, no. 5 (May 2020): 1620–23. http://dx.doi.org/10.1161/strokeaha.119.028108.
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Background and Purpose— Nonhuman primates are increasingly used in translational studies of ischemic stroke. However, current scoring systems in monkeys (eg, Nonhuman Primate Stroke Scale) do not focus on impairments in activities of daily living, so clinically relevant data are scarce for evaluating functional deficits in this model. Methods— Here, we referenced the modified Rankin Scale to provide a primate version of Rankin Scale (pRS) for ranking neurological dysfunction in monkeys following stroke. We selected hand function and strength, level of activity, and general mobility as the main components of pRS. We also analyzed interobserver variability. Results— pRS is a simple scale with only 6 levels. Functional deficit can be easily classified into none (category 0), slight (categories 1–2), moderate (category 3–4), and severe disabilities (category 5) based on pRS. We validated this scoring system on 11 monkeys, all with varying levels of neurological dysfunction following stroke, assessed by blinded testers. After a short training period, both technicians and neurology residents were able to achieve a high level of consistency using this scoring system. Conclusions— pRS is a simple and reliable functional scale, similar to the widely used modified Rankin Scale, for evaluating long-term neurological dysfunction in nonhuman primates. We recommend further validation studies and analyses.
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Sinagra, Marco, Costanza Aricò, Tullio Tucciarelli, Pietro Amato, and Michele Fiorino. "Coupled Electric and Hydraulic Control of a PRS Turbine in a Real Transport Water Network." Water 11, no. 6 (June 7, 2019): 1194. http://dx.doi.org/10.3390/w11061194.
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Although many devices have recently been proposed for pressure regulation and energy harvesting in water distribution and transport networks, very few applications are still documented in the scientific literature. A new in-line Banki turbine with positive outflow pressure and a mobile regulating flap, named Power Recovery System (PRS), was installed and tested in a real water transport network for the regulation of pressure and flow rate. The PRS turbine was directly connected to a 55 kW asynchronous generator with variable rotational velocity, and coupled to an inverter. The start-up tests showed how automatic adjustment of the flap position and the runner velocity variation are able to change the characteristic curve of the PRS according to the flow delivered by the water manager or to the pressure set-point assigned downstream or upstream of the system, maintaining good efficiency values in hydropower production.
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Ye, Qibin, Zhengda Kuang, and Guanjun Wang. "PLATE-ROD SYSTEM IN THE MANAGEMENT FOR PROGRESSIVE SCOLIOSIS IN GROWING CHILDREN." Journal of Musculoskeletal Research 12, no. 04 (December 2009): 213–23. http://dx.doi.org/10.1142/s0218957709002365.
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Objective: To study the therapeutic mechanism of an innovative instrumentation — Plate-Rod System for Scoliosis (PRSS) and its effectiveness for the surgical management of early onset scoliosis (EOS) and adolescent scoliosis (AIS). Method: A new device — PRSS was developed in our department. Between June 2000 and July 2008, 23 patients with progressive EOS, and from October 1998 to August 2003, a total of 66 AIS patients, who underwent one-stage PRSS procedure without bony fusion and had been followed up for more than two years, were evaluated prospectively. The mean age at the time of surgery was 7.98 years in the EOS group, and was 12.15 years in the AIS group. Experimental studies including X-ray analysis, photo-elastic test and type X collagen were used to test the therapeutic mechanism. Results: The subjects were followed up for more than 2 years. The mean scoliosis improved from 80.7° to 30.5° after surgery with a corrective rate of 62.2%. The length of the growth of the instrumented spine was on average 13.3 mm in EOS group. In AIS group, the mean precentage of correction was 68.86%. There were no severe complications in our studies. When PRSS was in place, compressive stress was found to exert on the convex side, while tensile stress on the concave side of the curvature, which was reflected by the changes in the color band in the photo-elastic test and the changes in the width of the disc spaces, and more type X collagen was expressed on the convex side than the concave side. This suggests that compressive stress leads to increase in earlier cartilage degeneration of end plate on the convex side, which is correlated with the decreased growth of the end plate of this side, resulting in maximum spinal realignment. Conclusion: The PRSS which dispenses with spinal fusion and allows extension along with the children's growth, is able to provide and maintain desirable correction of scoliosis in the later growing years due to its modulating efficiency in normalizing the spinal growth. This new device is an effective instrumentation for correcting scoliosis, especially for EOS.
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de Oliveira, Diulhio, and Marco Wehrmeister. "Using Deep Learning and Low-Cost RGB and Thermal Cameras to Detect Pedestrians in Aerial Images Captured by Multirotor UAV." Sensors 18, no. 7 (July 12, 2018): 2244. http://dx.doi.org/10.3390/s18072244.
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The use of Unmanned Aerial Vehicles (UAV) has been increasing over the last few years in many sorts of applications due mainly to the decreasing cost of this technology. One can see the use of the UAV in several civilian applications such as surveillance and search and rescue. Automatic detection of pedestrians in aerial images is a challenging task. The computing vision system must deal with many sources of variability in the aerial images captured with the UAV, e.g., low-resolution images of pedestrians, images captured at distinct angles due to the degrees of freedom that a UAV can move, the camera platform possibly experiencing some instability while the UAV flies, among others. In this work, we created and evaluated different implementations of Pattern Recognition Systems (PRS) aiming at the automatic detection of pedestrians in aerial images captured with multirotor UAV. The main goal is to assess the feasibility and suitability of distinct PRS implementations running on top of low-cost computing platforms, e.g., single-board computers such as the Raspberry Pi or regular laptops without a GPU. For that, we used four machine learning techniques in the feature extraction and classification steps, namely Haar cascade, LBP cascade, HOG + SVM and Convolutional Neural Networks (CNN). In order to improve the system performance (especially the processing time) and also to decrease the rate of false alarms, we applied the Saliency Map (SM) and Thermal Image Processing (TIP) within the segmentation and detection steps of the PRS. The classification results show the CNN to be the best technique with 99.7% accuracy, followed by HOG + SVM with 92.3%. In situations of partial occlusion, the CNN showed 71.1% sensitivity, which can be considered a good result in comparison with the current state-of-the-art, since part of the original image data is missing. As demonstrated in the experiments, by combining TIP with CNN, the PRS can process more than two frames per second (fps), whereas the PRS that combines TIP with HOG + SVM was able to process 100 fps. It is important to mention that our experiments show that a trade-off analysis must be performed during the design of a pedestrian detection PRS. The faster implementations lead to a decrease in the PRS accuracy. For instance, by using HOG + SVM with TIP, the PRS presented the best performance results, but the obtained accuracy was 35 percentage points lower than the CNN. The obtained results indicate that the best detection technique (i.e., the CNN) requires more computational resources to decrease the PRS computation time. Therefore, this work shows and discusses the pros/cons of each technique and trade-off situations, and hence, one can use such an analysis to improve and tailor the design of a PRS to detect pedestrians in aerial images.
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Huang, Wei Dong, and Yong Min Yu. "Design and Research on the Cigarette Paper Smoldering Rate of PRS-2 Tester." Advanced Materials Research 694-697 (May 2013): 1382–86. http://dx.doi.org/10.4028/www.scientific.net/amr.694-697.1382.
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The measuring body of PRS-2 cigarette paper smoldering rate tester is industrial vision sensors P4E1.3, it could determine and identify the burning of the cigarette paper by using the advanced computer image processing techniques.The vision sensor can detection to 10,000 times per minute when the image resolution is 1.3 million pixels-accurate, it simultaneously monitors the 5 cigarette paper, and can ensure that the scanning frequency of each cigarette paper is not lower than 100 Hz. In the case of deducting the necessary analysis and calculation time, it can guarantee that the timing accuracy is no less than 0.1s. The instrument is able of detecting the serrated depth of the burned cigarette paper line and excludes the misjudgment which caused by human factors,so it could achieve control, data analysis, save and print independently.
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Mihaljevic, Biljana, Vojin Vukovic, Natasa Milic, Teodora Karan-Djurasevic, Natasa Tosic, Tatjana Kostic, Irena Marjanovic, et al. "Comparative analysis of international prognostic index for chronic lymphocytic leukemia, progression-risk score, and MD Anderson Cancer Center 2011 score - a single center experience." Srpski arhiv za celokupno lekarstvo 149, no. 7-8 (2021): 415–21. http://dx.doi.org/10.2298/sarh201005047m.
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Introduction/Objective. Prognostication of chronic lymphocytic leukemia (CLL) has been substantially improved in recent times. Among several prognostic models (PMs) focused on the prediction of time to first treatment (TTFT), progression-risk score (PRS), and MD Anderson Cancer Center score 2011 (MDACC 2011) are the most relevant, while CLL-International Prognostic Index (CLL-IPI), although originally developed to predict overall survival (OS), is also being used to estimate TTFT. The aim of this study was to investigate CLL-IPI, PRS, and MDACC 2011 prognostic values regarding TTFT and OS. Methods. The analyzed cohort included 57 unselected Serbian CLL patients from a single institution, with the basic characteristics reflecting more aggressive disease than in the general de novo CLL population. The eligible patients were assigned investigated PMs, and TTFT and OS analyses were performed. Results. Patients with higher risk scores according to CLL-IPI, PRS, and MDACC 2011 underwent treatment significantly earlier than patients with lower risk scores (p = 0.002, p = 0.019, and p < 0.001, respectively). In multivariate analysis, MDACC 2011 and CLL-IPI retained their significance regarding TTFT (p = 0.001 and p = 0.018, respectively), while PRS did not. CLL-IPI was the only significant predictor of OS both at the univariate (p = 0.005) and multivariate (p = 0.013) levels. Conclusion. CLL-IPI, PRS, and particularly MDACC 2011 are able to predict TTFT even in cohorts with more advanced-disease patients, while for prediction of OS, CLL-IPI is the only applicable among the three PMs. These results imply that PMs should be investigated in more diverse CLL populations, as it is in real-life setting.
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Pita, Joana Sofia, Nuno Sousa, Borja Bartolome, Carlos Loureiro, and Ana Todo Bom. "Beer: an uncommon cause of anaphylaxis." BMJ Case Reports 12, no. 1 (January 2019): e227723. http://dx.doi.org/10.1136/bcr-2018-227723.
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Beer is one of the most consumed alcoholic beverages worldwide but allergic reactions to this beverage are uncommon. The authors present a case report of a 32-year-old male patient, sent to our Allergy and Immunology Department due to anaphylaxis minutes after Franziskaner beer ingestion. He tolerates all other alcoholic beverages. Prick tests to cereals were positive to wheat, corn and barley, as well as to peach. Prick-to-prick tests were performed with nine beer brands, all positive. Immunoglobulin (Ig)E to Pru p 3 was 14.8 kU/L. Sodium dodecyl sulfate polyacrylamide gel electrophoresis inhibition immunoblotting was performed with the Franziskaner beer extract in solid phase and both cereal extracts (wheat, barley and corn) and Pru p 3 as inhibitors. Extracts from wheat, barley and corn, and Pru p 3 purified protein were able to inhibit almost totally the IgE-binding to the Franziskaner beer extract. It seemed likely that the IgE-binding bands detected in the Franziskaner beer extract could be an LTP from cereals.
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Palanisamy, Navindra Kumari, Parasakthi Navaratnam, and Shamala Devi Sekaran. "Quintuplex PCR to Detect Antibiotic Resistance Genes in Streptococcus pneumoniae." Journal of Clinical and Health Sciences 1, no. 2 (December 31, 2016): 22. http://dx.doi.org/10.24191/jchs.v2i1.5861.
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Introduction: Streptococcus pneumoniae is an important bacterial pathogen, causing respiratory infection. Penicillin resistance in S. pneumoniae is associated with alterations in the penicillin binding proteins, while resistance to macrolides is conferred either by the modification of the ribosomal target site or efflux mechanism. This study aimed to characterize S. pneumoniae and its antibiotic resistance genes using 2 sets of multiplex PCRs. Methods: A quintuplex and triplex PCR was used to characterize the pbp1A, ermB, gyrA, ply, and the mefE genes. Fifty-eight penicillin sensitive strains (PSSP), 36 penicillin intermediate strains (PISP) and 26 penicillin resistance strains (PRSP) were used. Results: Alteration in pbp1A was only observed in PISP and PRSP strains, while PCR amplification of the ermB or mefE was observed only in strains with reduced susceptibility to erythromycin. The assay was found to be sensitive as simulated blood cultures showed the lowest level of detection to be 10cfu. Conclusions: As predicted, the assay was able to differentiate penicillin susceptible from the non-susceptible strains based on the detection of the pbp1A gene, which correlated with the MIC value of the strains.
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Carden, Rich, Bill Leaning, and Tony Joy. "Delivering Community Emergency Medicine during the COVID-19 pandemic: the Physician Response Unit." Emergency Medicine Journal 38, no. 5 (April 21, 2021): 371–72. http://dx.doi.org/10.1136/emermed-2020-210112.
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The COVID-19 pandemic has presented significant challenges to services providing emergency care, in both the community and hospital setting. The Physician Response Unit (PRU) is a Community Emergency Medicine model, working closely with community, hospital and pre-hospital services. In response to the pandemic, the PRU has been able to rapidly introduce novel pathways designed to support local emergency departments (EDs) and local emergency patients. The pathways are (1) supporting discharge from acute medical and older people’s services wards into the community; (2) supporting acute oncology services; (3) supporting EDs; (4) supporting palliative care services. Establishing these pathways have facilitated a number of vulnerable patients to access patient-focussed and holistic definitive emergency care. The pathways have also allowed EDs to safely discharge patients to the community, and also mitigate some of the problems associated with trying to maintain isolation for vulnerable patients within the ED. Community Emergency Medicine models are able to reduce ED attendances and hospital admissions, and hence risk of crowding, as well as reducing nosocomial risks for patients who can have high-quality emergency care brought to them. This model may also provide various alternative solutions in the delivery of safe emergency care in the postpandemic healthcare landscape.
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Ho, Theresa D., and Craig D. Ellermeier. "PrsW Is Required for Colonization, Resistance to Antimicrobial Peptides, and Expression of Extracytoplasmic Function σ Factors in Clostridium difficile." Infection and Immunity 79, no. 8 (May 31, 2011): 3229–38. http://dx.doi.org/10.1128/iai.00019-11.
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ABSTRACTClostridium difficileis an anaerobic, Gram-positive, spore-forming, opportunistic pathogen that is the most common cause of hospital-acquired infectious diarrhea. In numerous pathogens, stress response mechanisms are required for survival within the host. Extracytoplasmic function (ECF) σ factors are a major family of signal transduction systems, which sense and respond to extracellular stresses. We have identified threeC. difficileECF σ factors. These ECF σ factors, CsfT, CsfU, and CsfV, induce their own expressions and are negatively regulated by their cognate anti-σ factors, RsiT, RsiU, and RsiV, respectively. The levels of expression of these ECF σ factors increase following exposure to the antimicrobial peptides bacitracin and/or lysozyme. The expressions of many ECF σ factors are controlled by site 1 and site 2 proteases, which cleave anti-σ factors. Using a retargeted group II intron, we generated aC. difficilemutation inprsW, a putative site 1 protease. TheC. difficile prsWmutant exhibited decreased levels of expression of CsfT and CsfU but not of CsfV. When expressed in a heterologous host,C. difficilePrsW was able to induce the degradation of RsiT but not of RsiU. When theprsWmutant was tested in competition assays against its isogenic parent in the hamster model ofC. difficileinfection, we found that theprsWmutant was 30-fold less virulent than the wild type. TheprsWmutant was also significantly more sensitive to bacitracin and lysozyme than the wild type inin vitrocompetition assays. Taken together, these data suggest that PrsW likely regulates the activation of the ECF σ factor CsfT inC. difficileand controls the resistance ofC. difficileto antimicrobial peptides that are important for survival in the host.
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Sihombing, Rilies Diorita, and Fuad Erdansyah. "PENERAPAN WPAP DENGAN COREL DRAW PADA GANTUNGAN KUNCI BERBAHAN RESIN DI KELOMPOK UKM SUMATERA UTARA." Gorga : Jurnal Seni Rupa 9, no. 2 (December 16, 2020): 430. http://dx.doi.org/10.24114/gr.v9i2.21785.
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AbstrakPenelitian ini didasari dengan beragamnya peninggalan dan budaya visual yang ada di Sumatera Utara, seperti: Pakaian adat, rumah adat, kegiatan tradisonal, bangunan bersejarah. Keberagaman tersebut menjadi daya Tarik bagi para wisatawan yang berkunjung ke Sumatera Utara dengan memiliki souvenir yang unik dan modern yaitu dengan memvisualisasikan kedalam aliran gaya desain modern WPAP pada gantungan kunci. Setelah melakukan survei di Galeri Promosi Usaha Kecil Menengah (UKM), Sumut Pekan Raya Sumatera Utara (PRSU), tampak bahwa belum adanya penerapan WPAP pada gantungan kunci yang berbahan resin. Hal inilah yang melatar belakangi penelitian ini. Penelitian ini dilaksanakan dengan metode kuantitatif deskripsi dengan pendekatan esperimental. Dimana proses pembuatan produk diawali dengan pengenalan desain grafis dan aplikasi software Corel Draw, mengamati demonstrasi pembuatan WPAP terlebih dulu kemudian melakukan perancangan desain produk dan penerapan WPAP menjadi gantungan kunci berbahan resin. Hasil dari penelitian ini adalah produk gantungan kunci anomali budaya visual WPAP Sumatera Utara berbahan resin yang dibuat oleh para pelaku UKM dimana produk yang dibuat layak untuk diproduksi karena para pelaku UKM sudah memahami teori dan konsep dasar rancangan desain WPAP serta tahapan produksi dari pencetakan, hingga finishing produk. Dengan dilaksakannya penelitian ini diharapkan mampu membantu masyarakat terutama pelaku UKM dalam memperbaiki perekonomian yang kian merosot akibat pandemi Covid-19 serta memajukan pariwisata Sumatera Utara. Kata Kunci: desain, WPAP, cenderamata, resin, UKM.AbstractThis research is based on the variety of cultural heritage and visuals in North Sumatra, such as: traditional clothing, traditional houses, traditional activities, historical buildings. This diversity is an attraction for tourists visiting North Sumatra by having unique and modern souvenirs, namely by visualizing into the flow of the modern WPAP’s design style on the key chain. After conducting a survey at the PRSU North Sumatra SME Promotion Gallery, it appears that there is no WPAP application on key chains made from resin. This is the background of this research. This research was conducted using a descriptive qualitative method through an experimental approach. The manufacturing process begins with an introduction to graphic design and the Corel Draw software application, observing the demonstration of making WPAP first then designing the product design, and application the WPAP into a resin key chain. The result of this research is the product of the visual cultural anomaly key chain of the North Sumatra WPAP made from resin made by UKM players where the products made are feasible to be produced because the SMEs already understand the basic theories and concepts of WPAP design and production stages from printing to finishing product. By carrying out this research, it is hoped that it will be able to help the community, especially SME players, in improving the economy which is increasingly deteriorating due to the Covid-19 pandemic and advancing tourism in North Sumatera.Keywords: design, WPAP, souvenirs, resins, SME.
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Haji Seyed Abolghasem, Fatemeh, Juliana Othman, and Shanina Sharatol Ahmad Shah. "ENHANCED LEARNING: THE HIDDEN ART OF REFLECTIVE JOURNAL WRITING AMONG MALAYSIAN PRE-REGISTERED STUDENT NURSES." Journal of Nusantara Studies (JONUS) 5, no. 1 (January 30, 2020): 54–79. http://dx.doi.org/10.24200/jonus.vol5iss1pp54-79.
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Background and Purpose: Although the impact of reflective journal writing (RJW) on enhanced learning has a long history, studies on this pedagogical tool for enhanced learning are never exhausted. This study attempts to highlight enhanced self-directed learning through the use of reflective journal (RJ) among Malaysian diploma nursing students.
Methodology: For this study, eight purposefully selected pre-registered student nurses (PRSN) from a public college contributed over 54 reflective journal entries over two months. Through a qualitative content analysis, the journals were analyzed using a model devised by Mezirow (1990) that was previously used by Kember (1999), Chirema (2007), and Kear (2013) to identify the students’ levels of reflection of content/descriptive, process/practical, and premise/critical reflection resembling Transformative Learning Theory (TLT).
Findings: The findings suggested that RJ helps learners become in control of themselves from the early stage of a clinical environment. They expressed their appreciation towards collaborations and are grateful to be able to express their feelings and emotions of “fears” and “trust”. Further, they indicated their mindfulness to appreciate their levels of knowledge and skills through reflection upon the nursing tasks as they make themselves ready to be a future nurse. Furthermore, it was highlighted that feeling competent and being able to work independently and to make sound decisions would not be realized if they could not think critically from the initial stage of clinical environment.
Contributions: This research confirms that PRSN become more self-directed and highly motivated to develop critical thinking to dispose for their better lifelong learning through the use of reflective journals.
Keywords: Content reflection, levels of reflection, premise reflection, process reflection, reflective journal writing.
Cite as: Seyed Abolghasem, F., Othman, J., & Ahmad Shah, S. S. (2020). Enhanced learning: The hidden art of reflective journal writing among Malaysian pre-registered student nurses. Journal of Nusantara Studies, 5(1), 54-79. http://dx.doi.org/10.24200/jonus.vol5iss1pp54-79
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Getahun, Saleamlak. "Review of Inclusive Growth and other Alternatives to Confront Authoritarian Populism." Zeszyty Naukowe SGGW w Warszawie - Problemy Rolnictwa Światowego 17(32), no. 4 (December 29, 2017): 78–84. http://dx.doi.org/10.22630/prs.2017.17.4.83.
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Our world has gone through myriad forms of administrative and economic ideological eras, some of which helped positively and others contributed regressively. Recently, the rise of authoritarian populism as an alternative path to mainstream democracy stems from the failure of inclusiveness in the political and economic institutions especially in the rural world. Due to extractive capitalism, nowadays, rural areas are characterized by persistent poverty, deep inequalities, marginalization and exclusion, fractured identities and loss of self-esteem, which in turn engenders a regressive politics dubbed 'authoritarian populism'. It endangers our future unless we confront it and it has gained momentum by winning national elections in some countries. Alternatively, inclusive growth that would successfully share benefits to the rural people via inclusive political and economic institutions could be able to transform the rural poor. Endorsing and supporting this option with emancipatory rural politics, therefore, saves globalization from a looming collapse and ultimately culminates the world to a new level of civilization.
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Marišová, Eleonóra, Ján Gaduš, Martin Mariš, and Agnieszka Parlińska. "Legal Regulations and the Perspectives of Renewable Energy Policy in Selected EU Member States." Zeszyty Naukowe SGGW w Warszawie - Problemy Rolnictwa Światowego 18(33), no. 3 (September 28, 2018): 216–28. http://dx.doi.org/10.22630/prs.2018.18.3.80.
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The main objective of the paper is an evaluation of the development of the use of the RES in V4 countries compared to the EU-28 average and assessment, if national strategic goals regarding the share of the RES on gross inland energy consumption are achievable till 2020. To achieve the main aim of the paper it was decided to apply Brown triple exponential smoothing model as a main research method. Based on gathered results and using the extrapolation for making the forecast till do 2020 it was found out, that Slovakia might track the national target with point estimation of 16.25% (90% CI: 13.98:18.53), Czech Republic 12.75% (90% CI: 10.44:15.06), Poland 19.9% (90% CI: 16.42: 23.37). In case of Hungary, it might fail to reach the national target with point estimation of 10.42% (90% CI:8.87:11.98) and overall EU in average will not be able to reach common target with point estimation of 15.94% (90% CI:13.08:18.8).
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Gao, Wei, Yuen K. Ho, Julia Verne, Emma Gordon, and Irene J. Higginson. "Geographical and temporal Understanding In place of Death in England (1984–2010): analysis of trends and associated factors to improve end-of-life Care (GUIDE_Care) – primary research." Health Services and Delivery Research 2, no. 42 (November 2014): 1–104. http://dx.doi.org/10.3310/hsdr02420.
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BackgroundPlace of death (PoD) has been used as an outcome measure for end-of-life care. Analysis of variations in PoD can improve understanding about service users’ needs and thus better target health-care services.Objectives(1) To describe PoD in England by demographic, socioeconomic and temporal variables; (2) to determine how much of the variation in PoD can be explained by potential explanatory variables at the area level, and building on this to develop individual-level multivariable regression models; and (3) to evaluate factors associated with PoD and to construct risk assessment models to inform practice.MethodsA population-based study of all registered deaths between 1984 and 2010 in England (n = 13,154,705). The outcome was the PoD. Explanatory variables included age, gender, cause of death (CoD), marital status, year of death, whether or not the death was in a holiday period (Christmas, Easter, New Year), season of death, the location of usual residence and area-level deprivation. The proportion of explained variation in PoD was estimated using the weighted aggregate-level linear regression. Factors associated with PoD were investigated using generalised linear models. The risk assessment models were constructed using the 2006–9 data; the performance was evaluated using the 2010 data.ResultsHospital was the most common PoD in 2001–10 [overall 57.3%; range – cancer 46.1% to chronic obstructive pulmonary disease (COPD) 68.3%], followed by home [overall 19.0%; range – cerebrovascular disease (CBD) 6.7% to cardiovascular disease 27.4%] or care home (overall 17.2%; range – cancer 10.1% to neurological conditions 35.2%), depending on CoD. Over the period, the proportion of hospital deaths for people who died from non-cancer increased (57.1–61.2%) and care home deaths reduced (21.2% down to 20.0%); a reverse pattern was seen for those who died of cancer (hospital: reduced, 48.6–47.3%; care home: increased, 9.3–10.1%). Hospice deaths varied considerably by CoD (range – CBD 0.2% to cancer 17.1%), and increased slightly overall from 4.1% in 1993–2000 to 5.1% in 2001–10. Multivariable analysis found that hospital deaths for all causes combined were more likely for people aged 75+ years [proportion ratios (PRs) 0.863–0.962 vs. aged 25–54 years], those who lived in London (PRs 0.872–0.988 vs. North West), those who were divorced, single and widowed (PRs 0.992–1.001 vs. married), those who lived in more deprived areas (PRs 0.929–1.000 more deprived vs. less deprived) and those who died in autumn, winter or at New Year. We were able to develop risk assessment models but the areas under the receiver operating characteristic curve indicating poor predictive performance, ranging from 0.552 (COPD) to 0.637 (CBD).ConclusionsHospital remains the most common PoD, followed by home and care home. Hospices play an important role for people who died from cancer but little for other diseases. Place of death is strongly associated with the underlying CoD. The variation in PoD by region, age, marital status and area deprivation suggests that inequities exist, which services and clinical commissioning groups could seek to address.FundingThe National Institute for Health Services and Delivery Research programme.
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Kacprzak, Marzena, Agnieszka Król, and Marta Radziszewska. "European Integration Influence on the Development of Human Capital of Small and Medium Enterprises in Poland." Zeszyty Naukowe SGGW w Warszawie - Problemy Rolnictwa Światowego 18(33), no. 4 (December 28, 2018): 236–49. http://dx.doi.org/10.22630/prs.2018.18.4.114.
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Enterprises from the SME sector significantly affect the quality of human capital in Poland and the standards of their management are rising every year. The aim of this article is to present the essence and specifics of human capital of SMEs, showing the impact of European integration on the devel-opment of human capital in this sector. In addition, the authors focus on finding the answer to the question whether employers willingly reach for EU funding (sources of knowledge, forms, types of funding, barriers to access to funds) to be able to support and develop human capital that they have in the long run. The study was carried out by a survey method. The analysis made allowed to formu-late the following conclusions. Entrepreneurs willingly undertake to raise funds from EU funds. Re-spondents were convinced that EU funds help in the development of their businesses, although ob-taining funding alone is not easy. The respondents pointed to barriers, which include complicated and lengthy procedures, as well as low availability of information.
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Singh, Devesh, Zoltan Gal, Raqif Huseynov, and Michał Wojtaszek. "Determining the Performance Measurement of SME from Economic Value Added: Study on Hungary, Somogy County." Zeszyty Naukowe SGGW w Warszawie - Problemy Rolnictwa Światowego 18(33), no. 2 (July 2, 2018): 270–79. http://dx.doi.org/10.22630/prs.2018.18.2.54.
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EVA (Economic Value Added) permits commercial businesses to figure out whether the business is operating in profit and the money can be put into effect into a more profitable source. A leading EVA is a sign that the company has a greater value. The goal of this study is to identify if SMEs' actions carried out on a daily basis are able to generate economic value added for their business. The study is based on a comparative study between Hungary and 28 EU countries. The study is carried out in Hungary’s region of Somogy county. First, the variables for research were created and research was carried out at ground level. The research used the Expletory Factor analysis method to find EVA determinants. The results showed that determinants work together to reshape the regional industrial growth. The research demonstrated that finance and sluggish production are the major determinants in Somogy county. Entrepreneurs' skills and finance have the major impact, which means that to achieve a high growth in SMEs, policy makers have to solve these two problems and make the policy concentric toward finance and high skill development problem.
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Grabowska, Bożena, and Monika Radzymińska. "Ocena postaw prozdrowotnych konsumentów nabywających żywność w sklepach specjalistycznych." Zeszyty Naukowe SGGW w Warszawie - Problemy Rolnictwa Światowego 19(34), no. 1 (April 1, 2019): 192–203. http://dx.doi.org/10.22630/prs.2019.19.1.18.
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The aim of the paper was to assess pro-health attitudes of consumers purchasing food in specialist stores. The type and frequency of food purchase was determined and respondents were classified due to pro-health attitude. The research was conducted using personal interview. A total of 190 interviews were gathered. The results showed that for customers of specialist stores, healthiness of consumed food is significant. They pay attention to its ingredients buying natural products with low content of preservatives, less processed. These consumers are willing to pay more for guaranteed quality products. Three clusters of pro-health attitudes representing: 22, 18 and 60% of surveyed population were distinguished. Cluster 1 was represented mostly by men who do not care about the amount of calories consumed and do not interested in knowledge about healthy eating. This group pay attention on purchased food quality, and they are able to pay more for guaranteed quality products. Whereas cluster 2 focused mainly men with moderate pro-health attitudes, not interested in expanding nutrition knowledge. The most-represented cluster of 3 was predominantly women with strong pro-health attitudes, counting consumed calories, seeking and exploring healthy eating knowledge.
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Frieyadie, Frieyadie. "SYSTEMATIC LITERATURE REVIEW (SLR): DISEASE DETECTION IN MELONS USING DIGITAL IMAGE PROCESSING." Jurnal Riset Informatika 3, no. 1 (May 8, 2021): 75–80. http://dx.doi.org/10.34288/jri.v3i1.178.
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Systematic Literature Review (SLR) is a technique used in this study which is used to study techniques for identifying leaf diseases using digital images as a basis for obtaining an understanding of disease identification techniques in melon leaves with digital images. Based on data from the Central Statistics Agency for the last 3 years from 2017-2019, melon production has increased considerably. Melon production data in 2017 was 92.43 tons, in 2018 was 118,708 and in 2019, overall melon production was 122,105 tons collected from 34 provinces in Indonesia. The problem that is often encountered in melon cultivation is the presence of plant pests that can harm and not maximize the yields of farmers. Several viruses cause mosaic disease that infects Cucurbitaceae plants, namely Cucumber aphid borne yellows virus (CABYV), Cucumber green mottle mosaic virus (CGMMV), Cucumber mosaic virus (CMV), Papaya ringspot virus (PRSV), Squash mosaic virus (SqMV), Squash leaf curl virus (SLCV), Watermelon mosaic virus (WMV). Information technology has now developed to be able to manage digital image data to identify problems faced by farmers. Several classification methods that can be used to answer problems include SVM, Artificial Neural Network, Decision Tree, Convolutional Neural Network.
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Madaan, Jyoti, and Indu Kashyap. "A Novel Handoff Necessity Estimation Approach Based on Travelling Distance." International Journal of Advances in Applied Sciences 7, no. 2 (June 1, 2018): 105. http://dx.doi.org/10.11591/ijaas.v7.i2.pp105-116.
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<p><em>Mobility management is one of the most important challenges in Next Generation Wireless Networks (NGWNs) as it enables users to move across geographic boundaries of wireless networks. Nowadays, mobile communications have heterogeneous wireless networks offering variable coverage and Quality of Service (QoS). The availability of alternatives generates a problem of occurrence of unnecessary handoff that results in wastage of network resources. To avoid this, an efficient algorithm needs to be developed to minimize the unnecessary handoffs. Conventionally, whenever Wireless Local Area Network (WLAN) connectivity is available, the mobile node switch from cellular network to wireless local area network to gain maximum use of high bandwidth and low cost of wireless local area network as much as possible. But to maintain call quality and minimum number of call failure, a considerable proportion of these handovers should be determined. Our algorithm makes the handoff to wireless local area network only when the Predicted Received Signal Strength (PRSS) falls below a threshold value and travelling distance inside the wireless local area network is larger than a threshold distance.Through MATLAB simulation, we show that our algorithm is able to improve handover performance.<strong> </strong></em></p>
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Fehér, Anita, Péter Boross, Tamás Sperka, Gabriella Miklóssy, János Kádas, Péter Bagossi, Stephen Oroszlan, Irene T. Weber, and József Tözsér. "Characterization of the murine leukemia virus protease and its comparison with the human immunodeficiency virus type 1 protease." Journal of General Virology 87, no. 5 (May 1, 2006): 1321–30. http://dx.doi.org/10.1099/vir.0.81382-0.
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The protease (PR) of Murine leukemia virus (MLV) was expressed in Escherichia coli, purified to homogeneity and characterized by using various assay methods, including HPLC-based, photometric and fluorometric activity measurements. The specificity of the bacterially expressed PR was similar to that of virion-extracted PR. Compared with human immunodeficiency virus type 1 (HIV-1) PR, the pH optimum of the MLV enzyme was higher. The specificity of the MLV PR was further compared with that of HIV-1 PR by using various oligopeptides representing naturally occurring cleavage sites in MLV and HIV-1, as well as by using bacterially expressed proteins having part of the MLV Gag. Inhibitors designed against HIV-1 PR were also active on MLV PR, although all of the tested ones were substantially less potent on this enzyme than on HIV-1 PR. Nevertheless, amprenavir, the most potent inhibitor against MLV PR, was also able to block Gag processing in MLV-infected cells. These results indicate that, in spite of the similar function in the life cycle of virus infection, the two PRs are only distantly related in their specificity.
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Paulus Sihombing, Nur Hanifah Yuninda, and Massus Subekti. "MODIFIKASI PANEL KONTROL SISTEM PENYEDIA AIR DINGIN PADA SISTEM VENTILASI ZONA RADIASI MENENGAH." Journal of Electrical Vocational Education and Technology 2, no. 1 (March 21, 2020): 6–12. http://dx.doi.org/10.21009/jevet.0021.02.
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This research aims to design and make modifications to the control panel of cold water supply system in the
ventilation system into the radiation zone semi-automatic medium so as to increase the value of the effectiveness and efficiency of the operation pattern 3 cold water supply system.
This study uses research and development and implemented in PRSG GAS BATAN, PUSPIPTEK SERPONG in november 2015 until June 2016. Modification of the control panel is used, CDAQ NI 9132, NI 9205, and 14.0
Labview software which will display chiller work in real time in graphs and nominal. Hardware input consists of, selector to choose the working water supply system cold, RTD PT100 as readers temperature of water entering the inlet pipe and the temperature of the water that comes out of the chiller, and sensor current transformer as a reader of electric current in the circulation pump, the output device is composed of pilot
working as an indication lamp chiller and a thermostat to control the chiller via the inlet pipe. The steps to create the control panel modification of the draft, the control panel wiring, wiring input NI 9205, a program in
Labview, then perform tests on the device.
Based on the results of testing known that the thermostat is able to control the chiller in accordance with the limits of the temperature setting on the thermostat. In the test results of pembacan incoming water temperature at the inlet pipe through the display labview program has a percentage error of 0.52%, while data readings out of the water temperature chiller 1 has a percentage of the reading error of 0.57%, the second chiller is 0 , 41% and chiller 3 is 0.45% and the data of electric current readings on the circulation pump shown in labv iew program has a percentage of error of 1.24% in chiller 1, and 1.62% in the chiller 2, and 1.27% the chiller 3. Once the system has been tested as a whole, so that it can be concluded that the modification of the control panel of the cold water supply system can work properly according to the principles of work that has been made
Abstrak
Sistem penyedia air dingin yang berjumlah 3 unit pada PRSG GAS BATAN sebagai penghasil air dingin
memiliki pola pengoperasian secara manual yang kurang efektif dan efesisen sehingga kurang optimal. Penelitian ini bertujuan untuk merancang dan membuat modifikasi panel kontrol sistem penyedia air dingin pada sistem ventilasi zona radiasi menengah menjadi semi otomatis sehingga dapat meningkatkan nilai efektifitas dan efesiensi dari pola pengoperasian 3 sistem penyedia air dingin.
Penelitian ini menggunakan metode penelitian dan pengembangan dan dilaksanakan di PRSG GAS BATAN, PUSPIPTEK SERPONG pada bulan november 2015 sampai juni 2016. Modifikasi panel kontrol ini menggunakan, CDAQ NI 9132, NI 9205, dan software Labview 14.0 yang akan menampilkan kerja chiller secara real time dalam bentuk grafik dan nominal. Peralatan input terdiri dari, selektor untuk memilih kerja sistem penyedia air dingin, RTD PT100 sebagai pembaca suhu air yang masuk pada pipa inlet dan suhu air yang keluar dari chiller, dan sensor current trafo sebagai pembaca listrik pada pompa sirkulasi, peralatan output terdiri dari pilot lamp sebagai indikasi kerja chiller dan thermostat untuk mengontrol chiller melalui pipa inlet. Langkah-langkah pembuatan modifikasi panel kontrol dari membuat rancangan, wiring panel kontrol, wiring input NI 9205, program pada Labview, kemudian melakukan uji coba pada alat.
Berdasarkan hasil dari pengujian diketahui bahwa thermostat mampu mengontrol chiller sesuai dengan batas setting suhu pada thermostat. Pada hasil pengujian dari pembacan suhu air yang masuk pada pipa inlet melalui tampilan program labview memiliki presentase kesalahan sebesar 0,52%, sedangkan data hasil pembacaan suhu air keluar dari chiller 1 memiliki presentase kesalahan pembacaan sebesar 0,57%, pada chiller 2 ialah 0,41% dan chiller 3 ialah 0,45% dan data hasil pembacaan listrik pada pompa sirkulasi yang ditampilkan dalam program labview memiliki presentase kesalahan 1,24% pada chiller 1, dan 1,62% pada chiller 2, dan 1,27% pada chiller 3. Setelah sistem diuji secara keseluruhan, sehingga dapat disimpulkan bahwa modifikasi panel kontrol sistem penyedia air dingin dapat bekerja dengan baik sesuai prinsip kerja yang telah dibuat
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Ghafoor, Abdul, Khalid Mustafa, Khalid Mushtaq, and Abedullah Abedullah. "Cointegration and Causality: An Application to Major Mango Markets in Pakistan." LAHORE JOURNAL OF ECONOMICS 14, no. 1 (January 1, 2009): 85–113. http://dx.doi.org/10.35536/lje.2009.v14.i1.a4.
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Mangoes are one of Pakistan’s most important fruits; the country is the world’s fourth largest producer and exporter of mangoes. Integrated markets are those where price signals are transferred from one to another, allowing physical arbitrage to adjust any disturbances in these markets; integrated markets are thus a sign of efficiency. From this viewpoint, we investigate domestic integration among ten major mango markets, i.e., Lahore, Faisalabad, Multan, Gujranwala, Sargodha, Karachi, Hyderabad, Sukkur, Peshawar, and Quetta employing Johansen’s cointegration approach and error correction model. Data on monthly wholesale prices data (PRs/100 kg) were obtained from the agricultural and livestock marketing advisor, Government of Pakistan. The results of the study confirm the presence of integration among major mango markets in Pakistan. These markets were able to adjust for 16 to 68% of disequilibrium in one month, implying that it takes almost two to six months to remove any disequilibrium and to move back to long-run equilibrium. The Granger causality test shows that the Karachi market has bidirectional causality with Lahore, Faisalabad, Multan, Hyderabad, and Sukkur, and a unidirectional relationship with the rest. An impulse response analysis was also conducted to check the stability of these markets given a standard error shock to the Karachi base market.
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Tang, Jennifer H., Sam Phiri, Wingston Ng’ambi, Jamie W. Krashin, Linly Mlundira, Thom Chaweza, Bernadette Samala, Hannock Tweya, Mina C. Hosseinipour, and Lisa B. Haddad. "Factors Associated with Hormonal and Intrauterine Contraceptive Use among HIV-Infected Men and Women in Lilongwe, Malawi: A Cross-Sectional Study." Infectious Diseases in Obstetrics and Gynecology 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/5429316.
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Background. Understanding the factors associated with the use of hormonal and intrauterine contraception among HIV-infected men and women may lead to interventions that can help reduce high unintended pregnancy rates.Materials and Methods. This study is a subanalysis of a cross-sectional survey of 289 women and 241 men who were sexually active and HIV-infected and were attending HIV care visits in Lilongwe, Malawi. We estimated adjusted prevalence ratios (PRs) to evaluate factors associated with hormonal and intrauterine contraceptive use for men and women in separate models.Results and Discussion. 39.8% of women and 33.2% of men (p=0.117) reported that they were using hormonal or intrauterine contraception at last intercourse. Having greater than 3 children was the only factor associated with hormonal and intrauterine contraceptive use among men. Among women, younger age, not wanting a pregnancy in 2 years, being with their partner for more than 4 years, and being able to make family planning decisions by themselves were associated with hormonal and intrauterine contraceptive use.Conclusions. The men and women in our study population differed in the factors associated with hormonal and intrauterine contraceptive use. Understanding these differences may help decrease unmet FP needs among HIV-infected men and women.
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Villarruel, Antonia M., Taryn L. Gal, Brenda L. Eakin, Aisha Wilkes, and Jeffrey H. Herbst. "From Research to Practice: The Importance of Community Collaboration in the Translation Process." Research and Theory for Nursing Practice 24, no. 1 (February 2010): 25–34. http://dx.doi.org/10.1891/1541-6577.24.1.25.
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In order for effective interventions to make an impact on their target population, they must be successfully translated and disseminated to the organizations that will ultimately deliver them to those in need. ¡Cuídate!, a culturally based intervention to reduce HIV sexual risk among Latino youth, was identified by the Centers for Disease Control and Prevention’s (CDC) Prevention Research Synthesis (PRS) project as “best evidence” of intervention efficacy and selected as part of the CDC’s Replicating Effective Programs (REP). The REP process consisted of the design, development, and field-testing of the ¡Cuídate! program package in community-based, nonacademic settings. Project staff worked with CDC and community-based partners throughout the REP process. Community partners included a community advisory board (CAB) and four case agencies. Case agency staff participated in a facilitator training and subsequently implemented the ¡Cuídate! program at their respective agencies. Process evaluation findings showed that facilitators were able to effectively use program materials and implement the program with fidelity. Adolescent participants reported they liked the program and would recommend the project to others. Only slight modifications to program and training materials were necessary following evaluation. Lessons learned included the importance of interdisciplinary collaboration and utilizing the resources available from each collaborative partner.
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Sartorius, CA, GS Takimoto, JK Richer, L. Tung, and KB Horwitz. "Association of the Ku autoantigen/DNA-dependent protein kinase holoenzyme and poly(ADP-ribose) polymerase with the DNA binding domain of progesterone receptors." Journal of Molecular Endocrinology 24, no. 2 (April 1, 2000): 165–82. http://dx.doi.org/10.1677/jme.0.0240165.
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Ligand-activated progesterone receptors (PR) bind to DNA at specific progesterone response elements by means of a DNA binding domain (DBD(PR)) containing two highly conserved zinc fingers. DNA-bound PRs regulate transcription via interaction with other nuclear proteins and transcription factors. We have now identified four HeLa cell nuclear proteins that copurify with a glutathionine-S-transferase-human DBD(PR )fusion protein. Microsequence and immunoblot analyses identified one of these proteins as the 113 kDa poly(ADP-ribose) polymerase. The three other proteins were identified as subunits of the DNA-dependent protein kinase (DNA-PK) holoenzyme: its DNA binding regulatory heterodimers consisting of Ku70 and Ku86, and the 460 kDa catalytic subunit, DNA-PK(CS). DNA-PK that was 'pulled-down' by DBD(PR) on the affinity resin was able to (1) autophosphorylate Ku70, Ku86, and DNA-PK(CS), (2) transphosphorylate DBD(PR), and (3) phosphorylate a DNA-PK-specific p53 peptide substrate. DNA-PK was also able to associate with the DBD of the yeast activator GAL4. However, neither a PR DBD mutant lacking a structured first zinc finger (DBD(CYS)) nor the core DBD of the estrogen receptor (DBD(ER)) copurified DNA-PK, suggesting the interaction is not non-specific for DBDs. Lastly, we found that DNA-PK copurified with full-length human PR transiently expressed in HeLa cells, suggesting that the human PR/DNA-PK complex can assemble in vivo. These data show that DNA-PK and DBD(PR) interact, that DBD(PR) is a phosphorylation substrate of DNA-PK, and suggest a potential role for DNA-PK in PR-mediated transcription.
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Yip, Tameson, Jennifer Ford, Colleen Ramsower, Betty Glinsmann-Gibson, Ryan Robetorye, and Lisa Rimsza. "Improving Patient Value Through Cross-Country Collaboration." American Journal of Clinical Pathology 152, Supplement_1 (September 11, 2019): S126. http://dx.doi.org/10.1093/ajcp/aqz124.006.
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Abstract Introduction Lymph2Cx lymphoma cell-of-origin assay (LM2CX) was developed by the Lymphoma/Leukemia Molecular Profiling Project (LLMPP) to better categorize diffuse large B-cell lymphoma (DLBCL). NanoString has licensed the assay and is currently pursuing FDA approval. In the meantime, the test is offered exclusively as a lab-developed test (LDT) by the Mayo Clinic Molecular Diagnostics–Arizona Lab (MDAZL) to Mayo Clinic Enterprise patients. In order to comply with these restrictions, the normal workflow for Mayo Clinic Rochester has been modified as cases are sent to Arizona. Rochester consultants order LM2CX using their local laboratory information system (LIS). Slides are prepared by Rochester histology and then shipped to Arizona, where they are entered into the Arizona LIS and processed. In July 2018, we discovered numerous cases that were ordered but not shipped. Because this step took place at the LIS transition between Arizona and Rochester, it was not detected immediately. Methods Allied Health Staff (AHS) colleagues in Rochester and Arizona had the unique opportunity to collaborate. After Arizona AHS identified the problem, they reached out to the Rochester pathology reporting specialists (PRSs) and began a joint improvement project. Together, we were able to measure the impact of the problem, with Arizona auditing digitally, while Rochester audited physical cases. We found 29% of the cases were handled improperly over a 6-month time period. In order to eliminate the gap, Rochester implemented several improvements, including training, tagging all LM2CX cases, and huddle discussions, while Arizona AHS monitored the process digitally. Results Since implementation of improvements, we have had zero defects. Modifications to AHS/consultant training in Rochester will ensure continued success. Conclusions This intervention illustrates the importance of strong collaborations in order to quickly respond to testing issues and provide the greatest value to patients.
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Beatrix, Meike Elsye, and Novera Elisa Triana. "IMPROVEMENT BONDING QUALITY OF SHOE USING QUALITY CONTROL CIRCLE." SINERGI 23, no. 2 (July 12, 2019): 123. http://dx.doi.org/10.22441/sinergi.2019.2.005.
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Shoe industry development in the era of globalization is currently overgrowing. Therefore, every company should be able to compete strictly with other companies that produce the same products. Quality maintenance is having to be done by the company to survive in business competition. PT. ABC is a manufacturer of sports shoes. The company has a problem with bonding shoes not achieved company standard in the year 2017. This paper is focused on the improvement of bonding shoe quality by using a method of Quality Control Circle which applying quality control tools are like check sheet, Pareto diagram, fishbone diagram, and 5W + 1 H. Based on the research results obtained percentage improvements of quality bonding test of 21.15%. Cement stripping on the midsole is the most significant number of the bonding test failure in Laboratory that is as much as 26.33% or 218 prs from the total collapse of the overall bonding shoes. Based on the background, the purpose of this research is to find out the root causes of the failure of bonding test shoes. The limitations of this research are only improving processes in the department, which makes the bonding shoe quality does not achieve the company standard. After doing the analysis using the quality control tools and making the improvement process in the whole areas that the percentage of the bonding test cement stripping on midsole could be increased to 5.18%. Analysis of the results obtained by applying the method of Quality Control Circle is the improvement of the quality of the bonding shoe. So, the trust customers against the company may be obtained that would eventually increase the number of orders to the company.
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Sperka, Tamás, Gabriella Miklóssy, Yunfeng Tie, Péter Bagossi, Gábor Zahuczky, Péter Boross, Krisztina Matúz, Robert W. Harrison, Irene T. Weber, and József Tözsér. "Bovine leukemia virus protease: comparison with human T-lymphotropic virus and human immunodeficiency virus proteases." Journal of General Virology 88, no. 7 (July 1, 2007): 2052–63. http://dx.doi.org/10.1099/vir.0.82704-0.
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Bovine leukemia virus (BLV) is a valuable model system for understanding human T-lymphotropic virus 1 (HTLV-1); the availability of an infectious BLV clone, together with animal-model systems, will help to explore anti-HTLV-1 strategies. Nevertheless, the specificity and inhibitor sensitivity of the BLV protease (PR) have not been characterized in detail. To facilitate such studies, a molecular model for the enzyme was built. The specificity of the BLV PR was studied with a set of oligopeptides representing naturally occurring cleavage sites in various retroviruses. Unlike HTLV-1 PR, but similar to the human immunodeficiency virus 1 (HIV-1) enzyme, BLV PR was able to hydrolyse the majority of the peptides, mostly at the same position as did their respective host PRs, indicating a broad specificity. When amino acid residues of the BLV PR substrate-binding sites were replaced by equivalent ones of the HIV-1 PR, many substitutions resulted in inactive protein, indicating a great sensitivity to mutations, as observed previously for the HTLV-1 PR. The specificity of the enzyme was studied further by using a series of peptides containing amino acid substitutions in a sequence representing a naturally occurring HTLV-1 PR cleavage site. Also, inhibitors of HIV-1 PR, HTLV-1 PR and other retroviral proteases were tested on the BLV PR. Interestingly, the BLV PR was more susceptible than the HTLV-1 PR to the inhibitors tested. Therefore, despite the specificity differences, in terms of mutation intolerance and inhibitor susceptibility of the PR, BLV and the corresponding animal-model systems may provide good models for testing of PR inhibitors that target HTLV-1.
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Abu-Dakka, Fares J., Angel Valera, Juan A. Escalera, Mohamed Abderrahim, Alvaro Page, and Vicente Mata. "Passive Exercise Adaptation for Ankle Rehabilitation Based on Learning Control Framework." Sensors 20, no. 21 (October 31, 2020): 6215. http://dx.doi.org/10.3390/s20216215.
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Ankle injuries are among the most common injuries in sport and daily life. However, for their recovery, it is important for patients to perform rehabilitation exercises. These exercises are usually done with a therapist’s guidance to help strengthen the patient’s ankle joint and restore its range of motion. However, in order to share the load with therapists so that they can offer assistance to more patients, and to provide an efficient and safe way for patients to perform ankle rehabilitation exercises, we propose a framework that integrates learning techniques with a 3-PRS parallel robot, acting together as an ankle rehabilitation device. In this paper, we propose to use passive rehabilitation exercises for dorsiflexion/plantar flexion and inversion/eversion ankle movements. The therapist is needed in the first stage to design the exercise with the patient by teaching the robot intuitively through learning from demonstration. We then propose a learning control scheme based on dynamic movement primitives and iterative learning control, which takes the designed exercise trajectory as a demonstration (an input) together with the recorded forces in order to reproduce the exercise with the patient for a number of repetitions defined by the therapist. During the execution, our approach monitors the sensed forces and adapts the trajectory by adding the necessary offsets to the original trajectory to reduce its range without modifying the original trajectory and subsequently reducing the measured forces. After a predefined number of repetitions, the algorithm restores the range gradually, until the patient is able to perform the originally designed exercise. We validate the proposed framework with both real experiments and simulation using a Simulink model of the rehabilitation parallel robot that has been developed in our lab.
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Ortega, Lorenzo, Daniel Medina, Jordi Vilà-Valls, François Vincent, and Eric Chaumette. "Positioning Performance Limits of GNSS Meta-Signals and HO-BOC Signals." Sensors 20, no. 12 (June 25, 2020): 3586. http://dx.doi.org/10.3390/s20123586.
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Global Navigation Satellite Systems (GNSS) are the main source of position, navigation, and timing (PNT) information and will be a key player in the next-generation intelligent transportation systems and safety-critical applications, but several limitations need to be overcome to meet the stringent performance requirements. One of the open issues is how to provide precise PNT solutions in harsh propagation environments. Under nominal conditions, the former is typically achieved by exploiting carrier phase information through precise positioning techniques, but these methods are very sensitive to the quality of phase observables. Another option that is gaining interest in the scientific community is the use of large bandwidth signals, which allow obtaining a better baseband resolution, and therefore more precise code-based observables. Two options may be considered: (i) high-order binary offset carrier (HO-BOC) modulations or (ii) the concept of GNSS meta-signals. In this contribution, we assess the time-delay and phase maximum likelihood (ML) estimation performance limits of such signals, together with the performance translation into the position domain, considering single point positioning (SPP) and RTK solutions, being an important missing point in the literature. A comprehensive discussion is provided on the estimators’ behavior, the corresponding ML threshold regions, the impact of good and bad satellite constellation geometries, and final conclusions on the best candidates, which may lead to precise solutions under harsh conditions. It is found that if the receiver is constrained by the receiver bandwidth, the best choices are the L1-M or E6-Public Regulated Service (PRS) signals. If the receiver is able to operate at 60 MHz, it is recommended to exploit the full-bandwidth Galileo E5 signal. In terms of robustness and performance, if the receiver can operate at 135 MHz, the best choice is to use the GNSS meta-signals E5 + E6 or B2 + B3, which provide the best overall performances regardless of the positioning method used, the satellite constellation geometry, or the propagation conditions.
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Goodison, S., S. Kenna, and S. J. H. Ashcroft. "Control of insulin gene expression by glucose." Biochemical Journal 285, no. 2 (July 15, 1992): 563–68. http://dx.doi.org/10.1042/bj2850563.
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Northern-blot analysis was used to demonstrate that an increase in extracellular glucose concentration increased the content of preproinsulin mRNA 2.3-fold in the beta-cell line HIT T15. A probe for the constitutively expressed glyceraldehyde-3-phosphate dehydrogenase was used as a control. Mannoheptulose blocked this effect of glucose. A stimulatory effect on preproinsulin mRNA levels was also observed in response to mannose and to 4-methyl-2-oxopentanoate. However, galactose and arginine were ineffective. Glucagon, forskolin and dibutyryl cyclic AMP also elicited an increase in HIT-cell preproinsulin mRNA. The ability of the 5′ upstream region of the preproinsulin gene to mediate the effect of glucose and other metabolites on transcription was studied by using a bacterial reporter gene technique. HIT cells were transfected with a plasmid, pOK1, containing the upstream region of the rat insulin-1 gene (-345 to +1) linked to chloramphenicol acetyltransferase (CAT). Co-transfection with a plasmid pRSV beta-gal containing beta-galactosidase driven by the Rous sarcoma virus promoter was used as a control for the efficiency of transfection; expression of CAT activity in transfected HIT cells was normalized by reference to expression of beta-galactosidase. Glucose caused a dose-dependent increase in expression of CAT activity, with a half-maximal effect at 5.5 mM and a maximum response of 4-fold. Mannoheptulose blocked this effect of glucose. Other metabolites (mannose, 4-methyl-2-oxopentanoate and leucine plus glutamine) were also able to increase insulin promoter-driven CAT expression, but galactose and arginine were ineffective. The stimulatory effect of glucose on CAT expression was not blocked by verapamil and was inhibited by increasing extracellular Ca2+ from 0.4 to 5 mM. Both dibutyryl cyclic AMP and forskolin caused an increase in insulin promoter-driven gene expression in the presence of 1 mM-glucose, but neither agent further increased the level of expression occurring in the presence of a maximally stimulating glucose concentration. The phorbol ester phorbol 12-myristate 13-acetate (PMA) also increased insulin promoter-driven CAT expression in the presence of 1 mM-, but not 11 mM-glucose. Staurosporine blocked the stimulatory effect not only of PMA but also of glucose and of dibutyryl cyclic AMP. We conclude that the 5′ upstream region of the insulin gene contains sequences responsible for mediating the stimulatory effect of glucose on insulin-gene transcription.(ABSTRACT TRUNCATED AT 400 WORDS)
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Scott, Roderick E. M., X. Sharon Wu-Peng, Paul M. Yen, William W. Chin, and Donald W. Pfaff. "Interactions of Estrogen- and Thyroid Hormone Receptors on a Progesterone Receptor Estrogen Response Element (ERE) Sequence: a Comparison with the Vitellogenin A2 Consensus ERE." Molecular Endocrinology 11, no. 11 (October 1, 1997): 1581–92. http://dx.doi.org/10.1210/mend.11.11.0003.
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Abstract The identification of hormone response elements in the promoter regions of hormonally regulated genes has revealed a striking similarity between the half-site of the estrogen-response element (ERE) and a consensus sequence constituting the thyroid hormone-response element. Because of the potential for thyroid hormone (T3) to affect estrogen (E)- and progesterone-dependent female reproductive behavior via EREs, we have begun to investigate the activity of an ERE identified in the progesterone receptor (PR) proximal promoter and its interactions with the estrogen receptor (ER) and thyroid hormone receptors (TR). In addition, we have compared ER and TR interactions on the PR ERE construct with that of the vitellogenin A2 (vit A2) consensus ERE. Electrophoretic mobility shift assays demonstrated that TR binds to the PR ERE as well as to the consensus ERE sequence in vitro. Further, these two EREs were differentially regulated by T3 in the presence of TR. T3 in the presence of TRα increased transcription from a PR ERE construct ∼5-fold and had no inhibitory effect on E induction. Similarly, T3 also activated a β-galactosidase reporter construct containing PR promoter sequences spanning −1400 to +700. In addition, the TR isoforms β1 and β2 also stimulated transcription from the PR ERE construct by 5- to 6-fold. A TRα mutant lacking the ability to bind AGGTCA sequences in vitro failed to activate transcription from the PR ERE construct, demonstrating dependence on DNA binding. In contrast to its actions on the PR ERE construct, TRα did not activate transcription from the vit A2 consensus ERE but rather attenuated E-mediated transcriptional activation. Attenuation from the vit A2 consensus ERE is not necessarily dependent on DNA binding as the TRα DNA binding mutant was still able to inhibit E-dependent transactivation. In contrast to TRα, the isoforms TRβ1 and TRβ2 failed to inhibit E-induced activation from the vit A2 consensus ERE. These results demonstrate that the PR ERE construct differs from the vit A2 consensus ERE in its ability to respond to TRs and that divergent pathways exist for activation and inhibition by TR. Since ERs, PRs, and TRs are all present in hypothalamic neurons, these findings may be significant for endocrine integration, which is important for reproductive behavior.
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David, Kevin A., Mitchell R. Smith, Izidore S. Lossos, Eren Roubal, Jane N. Winter, Steve T. Rosen, Leo I. Gordon, and Andrew M. Evens. "A Phase II Trial of Combination Bortezomib (Velcade®) and Rituximab for Untreated “High Tumor Burden” Indolent Non-Hodgkin Lymphoma (NHL)." Blood 112, no. 11 (November 16, 2008): 2004. http://dx.doi.org/10.1182/blood.v112.11.2004.2004.
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Abstract Traditional therapy for patients with symptomatic and/or high-risk indolent NHL most commonly includes rituximab combined with multiagent cytotoxic chemotherapy. However some patients are not able to tolerate chemotherapy due to advanced age and/ or co-morbidities. Further, combination of novel, targeted agents (non-chemotherapeutic) have been infrequently tested in newly diagnosed indolent NHL patient populations. Overall response rate (ORR) with single-agent rituximab in prior data for untreated indolent NHL was 73% with a complete remission (CR) rate of 37% following maintenance therapy (JCO2002; 20: 4261), although a good portion of patients in that series had low tumor burden at study entry. We hypothesized that frontline bortezomib and rituximab therapy would be effective and well tolerated for untreated “high tumor burden” indolent NHL. We have conducted a Simon 2-stage phase II trial for untreated indolent NHL. All patients were required to have “high tumor burden” as defined by Groupe D’Etude des Lymphomes Folliculaires (GELF) criteria. Induction therapy consisted of 3 cycles: bortezomib given at 1.6 mg/m2 days 1, 8, 15, and 22 q35 days for all 3 cycles and rituximab at 375 mg/m2 x 4 weekly doses for cycle 1, then day 1 only for cycles 2 and 3. Abbreviated consolidation therapy was subsequently given with 1 dose of each drug q2 months x 8 months. Responses were assessed by computerized tomography (CT) according to Cheson criteria (JCO 1999). We report here the results of the first stage of this 2-stage trial. Twenty-two patients have enrolled, of whom 17 were in the 1st stage. There were 9 women and 8 men; median age was 63 years (range 46–78 years). 14 patients had follicular lymphoma (FL), 2 marginal zone lymphoma, and 1 small lymphocytic lymphoma. 13 of 17 patients had stage IV disease and 4 had stage III. The median Follicular Lymphoma International Prognostic Index (FLIPI) was 3 (range 1–4) and the median follow-up was 13 months (range 1–24 months). Responses according to cycle number are shown in Table 1. After only 1 cycle, the ORR was 29% (all partial remissions (PRs)) with 71% stable disease (SD). Following cycle 3, ORR was 59% (24% CR). From cycle 1 to 3, 4/5 PRs converted to CR, 6 SDs converted to PR, while 1 PR and 4 SDs progressed or were removed from the study at physician discretion. 8 of 12 eligible patients have completed consolidation therapy. Following consolidation, 1 PR converted to CR and 2 SDs converted to PR for an ORR of 71%. According to histology, the ORR among FL patients after consolidation therapy was 86% (CR 36%, PR 50%). Therapy was very well tolerated. Grade 3 toxicities seen were lymphopenia, partial small bowel obstruction, and fatigue (all in 1 patient); no grade 4 toxicities occurred. Furthermore, no cytopenias or neurotoxicity was seen. Accrual to the 2nd stage is being completed. In summary, we found in the 1st stage of this phase II trial that bortezomib/rituximab combination therapy for untreated high tumor burden indolent NHL is well tolerated and active. Response rates improved throughout therapy (i.e., from cycle 1 through consolidation), although the CR rate achieved was low compared with chemotherapy-based regimens. Chemotherapy-based therapy should be considered standard therapy for frontline “high tumor burden” indolent NHL, although non-chemotherapy options may be considered for patients not anticipated to tolerate intensive therapy. Furthermore, responses seen here with bortezomib/rituximab, in a uniform high tumor burden patient population, were similar to rituximab alone in lower tumor burden populations. Analysis of clinical trials/reports in indolent NHL should include critical assessment of patient selection and future trials in high tumor burden should incorporate novel therapies into rituximab-chemotherapy based regimens. Table 1. Response according to cycle/treatment. After Cycle 1 After Cycle 3* Following consolidation therapy** *Three patients had PD, while 2 patients were taken off study (without PD) at physician discretion. **Eight of 12 eligible patients have completed post-induction therapy. ORR 29% (5/17) 59% (10/17) 71% (12/17) CR 0% 24% (4/17) 30% (5/17) PR 29% (5/17) 35% (6/17) 41% (7/17) SD 71% (12/17) 12% (2/17) 0% PD/off trial 0% 29% (5/17) 29% (5/17)
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Osuji, Nnenna, Ilaria Del Giudice, Estella Matutes, Claire Dearden, and Daniel Catovsky. "Alemtuzumab for Chronic Lymphocytic Leukemia with and without p53 Deletions." Blood 104, no. 11 (November 16, 2004): 2510. http://dx.doi.org/10.1182/blood.v104.11.2510.2510.
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Abstract Treatment of patients with chronic lymphocytic leukemia (CLL) who show p53 mutations or deletions remains problematic. Conventional agents such as chlorambucil, fludarabine and rituximab are ineffective in this sub-group. Possible therapeutic options for such patients include alemtuzumab and/or high dose methlylprednisolone. The literature provides 2 pieces of evidence; an initial case report (Stilgenbauer et al, New England Journal of Medicine. 2002; 347:452–3), and more recently a case series of 36 patients (Lozanski et al, Blood2004.103: 3278–81), describing the response of patients with p53 deletions to alemtuzumab. We review the treatment of 26 patients using alemtuzumab, and focus on responses in relation to the presence or absence of p53(17p) deletions as detected by fluorescence in situ hybridization (FISH). The patients were treated with alemtuzumab (CAMPATH-1H) between 1994 and 2004. This included 25 men and 1 woman with median age at diagnosis of 50 years (range 27–74). 8 patients had p53 deletion (31%). The group was heavily pre-treated with a median of 4 previous agents (range 1–11) which included fludarabine in 92% and autologous stem cell transplantation in 8%. Alemtuzumab was used 61 months from diagnosis (range 2.4–329.9) for Binet stage B or C disease (22 patients) with 3 patients receiving alemtuzumab during the terminal phase of their CLL. Duration of treatment ranged from 1 to 12 weeks with a median dose of 695mg. Three patients are still on treatment. Responses are currently evaluable in 23 patients. Good clinical responses (CR/PR) as assessed by revised NCI criteria, were documented in 12 patients (52%) and included 5 CRs, and 7 PRs. All CRs were observed in the p53 negative group although 1 patient with p53 deletion achieved CR in every respect except for mild anemia (Hb 10.2g/dl). Overall responses were seen in 3 of 7 (43%) patients with p53 deletions, and 9/16 (56%) of those without (NS) and lasted 4.1 months (range 2.8–22.2). Compared with prior agents, alemtuzumab was able to induce equivalent best responses in 7 patients or superior responses in 7 patients. In 8 of 9 cases where responses were inferior, alemtuzumab was able to transiently control the disease. Notably six patients were safely retreated with alemtuzumab with one patient receiving up to 4 courses. Toxicity was observed in 10 patients with asymptomatic CMV reactivation in 4, cytopenias with infection in 4 and anorexia in 1. One patient had evidence of pulmonary CMV, which contributed to his death. There were two other deaths due to progressive disease while on treatment. Alemtuzumab was able to induce responses in patients with progressive, refractory CLL, regardless of p53 status. Catovsky et al (ASH abstract submitted) observed few responses to conventional chemotherapy in CLL patients with >20% cells possessing 17p deletion. In the majority of our patients (6/7 cases), p53 was deleted in >20% of lymphocytes (range 36% – 91% of cells). All three PR’s in our series were seen in the patients in whom >20% of lymphocytes had p53 deletion. Responses to alemtuzumab even in these patients, provides a rationale for pre-emptive identification of this sub-group to prevent unnecessary exposure to toxicity from less effective agents and/or delayed use of alemtuzumab following multiple previous lines of therapy.
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Isambert, N., G. Spitaleri, P. Fumoleau, C. Noberasco, C. Ramazeilles, M. Chadjaa, L. Bolloni, and F. De Braud. "A phase I dose escalation safety and pharmacokinetic (PK) study of SSR244738 administered as a one-hour intravenous (IV) infusion twice-weekly during a 3-week cycle in patients (pts) with refractory solid tumors." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 2539. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.2539.
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2539 Background: SSR244738 is a new cytotoxic agent (G2-cell cycle inhibitor). In this first in man study the original schedule of administration was an IV infusion once every 3 weeks (Q3W); and due to the high clearance variability, 1300 mg/m2 was considered the maximum administered dose (MAD). The study was amended to test the twice weekly schedule (D1-D4-D8-D11-D15, every 3 weeks). Methods: Standard escalation was used in cohorts of 3–6 pts. PK profiles (up to T48h or T96h) were obtained in each pt after the 1st and the 5th administration (D1 and D15) of Cycle 1. In the Q3W, there was a trend to lower clearance (CL) in CYP2C9 *3/*3 and *1/*3 genotype pts therefore genotype samples were analyzed at baseline to identify poor metabolizers (PM) and adjust-dosing accordingly. Results: 22 heavily pretreated patients received SSR244738 at doses of 200 (3 pts), 280 (4 pts), 400 (3 pts), 560 (3 pts), 780 (3 pt), 1000 (6 pts; one pt was a PM and received 500 mg/m2). 15 females, 7 males, median age: 60 years (29–82), ECOG: (0:12, 1:9, Unk:1). Main tumor types: ovary, lung, breast, colon and prostate. Nb cycles/pts: > 2 cycles/21 (95%), > 4 cycles/9 (41%), > 6 cycles/6 (27%), > 8 cycles/2 (9%). The most common reason for treatment discontinuation was disease progression. DLT was seen in 2 pts at 1000 mg/m2 dose level: one patient had febrile neutropenia associated with Grade 3 mucositis and the second patient had Grade 3 neutropenia, which caused a treatment delay. Both pts showed high SSR244738 plasma exposures on D15. SD was reported in 11 patients. No CRs or PRs were observed. SSR244738 exhibited an overall low plasma CL (mean [range]: 0.9 [0.3–2.1] L/h). CL slightly decreased with repeated administration. The distribution volume was low [Vss mean (CV%): 11.6 L (30%)] and the terminal half life was long [mean (CV%): 15.6 h (58%)]. No deviation from dose proportionality could be observed, despite the moderate-to-high inter-individual variability (CV<64%) in exposure. Conclusions: SSR244738 is well tolerated with PK profile similar to the Q3W schedule; by changing the schedule of administration we were able to reach the MAD dose (5000 mg/m2/cycle). [Table: see text]
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Di Carlo, Brian A., Jessica L. Stern, Michael Schuster, Tsiporah Shore, John Harpel, Roger Pearse, Faiza Zafar, et al. "Breaking the Plateau Response in Myeloma: Preliminary Results of a Phase II Pilot Study of Sequential Bortezomib in Combination with Dexamethasone and Pegylated Liposomal Doxorubicin (DoVeD) in Patients No Longer Responsive to Standard Induction Regimens." Blood 108, no. 11 (November 16, 2006): 3538. http://dx.doi.org/10.1182/blood.v108.11.3538.3538.
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Abstract Thalidomide/lenalidamide with dexamethasone and vincristine/doxorubicin/ dexamethasone (VAD) are induction regimens for the treatment of MM. While most patients (pts) respond, the majority do not achieve a complete response (CR). In randomized trials, several groups have shown that meaningful responses (i.e. CR, near CR, and very good PR) correlate with longer survival. Our group has thus looked for methods to increase the percentage of pts achieving CRs by incorporating sequential, non cross-resistant agents. Bortezomib in combination with dexamethasone is superior to dexamethasone alone for relapsed/refractory multiple myeloma. The liposomal formulation of doxorubicin (Doxil) has significant anti-myeloma activity and less risk of toxicity compared with standard anthracyclines. This study was designed to treat patients whose response had reached a plateau (<25% change in paraprotein x 3 sequential determinations) in partial remission with initial induction regimens (lenalidomide/dexamethasone, thalidomide, thalidomide/dexamethasone, and VAD) to determine whether the introduction of bortezomib/dexamethasone +/− pegylated liposomal doxorubicin for six cycles (DoVeD study) can further cytoreduce and improve quality of the response. Pts’ initial treatments consisted of either BiRD (Biaxin, Revlimid, dexamethasone), thalidomide/dexamethasone or VAD received in the community setting. All pts enrolled on the study were intended to proceed into autologous stem cell transplantation. Pts were treated for six 21-day cycles receiving bortezomib at 1.3 g/m2 on days 1, 4, 8, and 11, with three, four day pulses of high dose dexamethasone. If a PR or better was not achieved after cycle 2, pts received liposomal doxorubicin on day four of every cycle. Pts who did not achieve a CR by the end of cycle four, received day four liposomal doxorubicin for cycles five and six. Eleven pts have been accrued to the study, eight of which have completed all six cycles and are evaluable. There have been 5 CRs and 3 PRs as determined by standard criteria. One pt who achieved a CR had the (4,14) translocation. Five out of the eight pts had the chromosome 13 deletion. Four of these five pts achieved a CR, three of whom have achieved a cytogenetic CR (standard cytogenetics and FISH). All pts were able to move on to autologous stem cell transplantation. Expected toxicities were seen with the high dose corticosteroids (fatigue, muscle weakness, insomnia, myalgias, hyperglycemia all grade 1–2). One pt required a dose reduction of the dexamethasone. Cytopenias were limited to grade 1 and 2 as was peripheral neuropathy. No further dose reductions were necessary. In conclusion, the DoVeD regimen is able to break the plateau typical of pts receiving standard induction therapy, inducing further cytoreduction. Our data suggest that pts with chromosome 13 deletion, in particular, may benefit from bortezomib as part of their up-front induction therapy. Though further study of this approach is warranted, the evidence suggests a possible paradigm shift for induction therapy in general. Non cross-resistant agents given in tandem can increase the percentage of patients achieving CR.
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Frasci, G., P. Comella, G. Scoppa, C. Guida, A. Gravina, F. Fiore, R. Casaretti, A. Daponte, A. Parziale, and G. Comella. "Weekly paclitaxel and cisplatin with concurrent radiotherapy in locally advanced non-small-cell lung cancer: a phase I study." Journal of Clinical Oncology 15, no. 4 (April 1997): 1409–17. http://dx.doi.org/10.1200/jco.1997.15.4.1409.
Full textAbstract:
PURPOSE Both cisplatin (CDDP) and paclitaxel have shown good antitumor activity in non-small-cell lung cancer (NSCLC) patients and are able to potentiate the antitumor effects of radiation therapy (RT). This study aimed to determine the maximum-tolerated doses (MTDs) of CDDP and paclitaxel (escalated alternately) when given concurrently with RT and to define the nature of the dose-limiting toxicity (DLT). PATIENTS AND METHODS Chemotherapy-naive patients with locally advanced NSCLC received six weekly administrations of a CDDP-paclitaxel combination with concurrent local RT. The starting doses of CDDP and paclitaxel were 30 mg/m2/wk and 35 mg/m2/wk, respectively. RT was initially given at the dose of 1.2 Gy twice daily for 5 days per week for 5 weeks (total dose, 60 Gy) and at a single daily dose of 2 Gy for 5 days per week for 6 weeks in the last two cohorts of patients. The drug doses were escalated alternately until DLT occurred in more than one third of the patients in a given cohort. RESULTS Overall, 25 patients were recruited through five different cohorts. All were assessable for toxicity. Esophagitis was the main toxicity and occurred in 16 of 25 patients (64%) and was grade 3 or 4 in five of them. At step 3 (CDDP 35 mg/m2/wk and paclitaxel 45 mg/m2/wk), two of five patients had to discontinue treatment because of severe esophagitis and one of these died of complications related to grade 4 esophagitis. However, keeping the same doses of chemotherapy and replacing hyperfractionation with a standard single-day fraction, weekly doses of CDDP and paclitaxel of 35 mg/m2 and 45 mg/m2 could be safely administered. Neutropenia was by far the most relevant hematologic toxicity and occurred in 33 of 141 weekly delivered courses, but it was of grade 4 in only four courses. Substantial pulmonary or neurologic toxicity was not observed in this study. Two complete responses (CRs) and 13 partial responses (PRs) were observed, for a 60% overall response rate (95% confidence interval [CI], 39% to 79%). The median survival time was 16 months, with a 66% 1-year survival probability. CONCLUSION CDDP 35 mg/m2/wk and paclitaxel 45 mg/m2/wk can be safely administered with concurrent standard RT. The use of hyperfractionation is associated with a more frequent occurrence of severe esophagitis and requires a reduction of the CDDP dose to 30 mg/m2/ wk. Only future randomized trials will elucidate which of these two approaches (standard or hyperfractionated RT) is the better option to improve the outcome of patients with locally advanced NSCLC.
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Fibach, Eitan, and Eliezer A. Rachmilewitz. "The In Vitro and In Vivo Effects Of Fermented Papaya Preparation On Radiation Exposure." Blood 122, no. 21 (November 15, 2013): 4929. http://dx.doi.org/10.1182/blood.v122.21.4929.4929.
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Abstract Background Various forms of radiation (radioactive, UV) cause cellular damage, which may lead to premature cell death or accumulation of somatic mutations which may lead to initiation and progression of malignancy. The damage is mediated in part by free radicals, particularly reactive oxygen species (ROS) (Reizenstein, Med Oncol Tumor Pharmacother. 1991;8:229). Fermented papaya preparation (FPP) is a product of yeast fermentation of Carica papaya Linn. FPP has been shown to have anti-oxidative potential by scavenging ROS, as well as by chelating excess iron (Prus & Fibach J Biol Regul Homeost Agents. 2012;26:203). Free iron species, such as the labile iron pool (LIP), participate in chemical reactions that generate ROS (Haber-Weiss and Fenton reactions). We studied the potential effect of FPP in preventing radiation-induced damage to various intracellular components in cultured human fibroblasts and myeloid leukemia (HL60) cells and in mice. Methods Cultured cells, human foreskin fibroblasts and myeloid leukemia (HL-60), were irradiated at various doses (0-18 Gy (Gammacell® 220, MDS Nordion, Excel, Canada). FPP (Osato Research Institute, Gifu, Japan) (10-100 µg/ml, was added either before or after irradiation. The cells were assayed after 1-3 days: Their survival was estimated by CellTiter 96® Aqueous Non-Radioactive Cell Proliferation assay. Apoptosis was determined by staining for phosphatidylserine exposure (by fluorescent Annexin V) and for intracellular uptake of propidium iodide. ROS was measured by staining with dichlorofluoresceine diacetate, and the LIP - with calcein-AM. The effects on the DNA were estimated by measuring 8-oxyguanine (a marker of DNA oxidation), using a fluorescent specific probe, and DNA instability was measured by the “comet assay”, a single-cell gel electrophoresis procedure. Apoptosis, ROS, LIP and 8-oxyguanine were quantified by flow cytometry. Experiments were also carried out on irradiated mice treated with FPP (by adding it to the drinking water) either before or after irradiation. The above mentioned parameters were assayed in their bone marrow cells in addition to determining their survival. Results The results indicated that FPP has significant (P<0.05) ameliorating effects on radiation-induced increase of LIP and generation of ROS, as well as on the generation of 8-oxyguanine and DNA instability. In addition, apoptosis was decreased and consequently the survival of the cells was increased (Fig. 1A). Moreover, about 60% of 14 Gy-irradiated mice that received 100 mg/ml of FPP in their drinking water were still alive after 30 days (Fig. 1B). Conclusions FPP was able to protect the short-term effects of radiation on cultured cells by increasing their viability. A similar effect was found in mice. The improvement in DNA instability induced by FPP may influence the long-term effects of radiation, such as the development of secondary leukemia, in patients who receive radiotherapy for their primary tumors. Disclosures: Fibach: Osato Research Institute, Gifu, Japan: Consultancy, Research Funding. Rachmilewitz:Osato Research Institute, Gifu, Japan: Consultancy, Research Funding.
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Venugopal, Parameswaran, Stephanie A. Gregory, Teresa Obrien, Ray Drasga, and Robert Bayer. "Phase II Study of 2-Weekly CHOP+Rituximab Followed by Yttrium 90 Ibritumomab Tiuxetan (Zevalin) in Patients with Previously Untreated Diffuse Large B Cell Lymphoma (DLBCL)." Blood 110, no. 11 (November 16, 2007): 4507. http://dx.doi.org/10.1182/blood.v110.11.4507.4507.
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Abstract Interval reduction from 3 to 2 weeks (CHOP-14; Pfreundschuh et al, Blood, 2004), addition of Rituximab to CHOP-21 (R-CHOP-21, Coiffier et al NEJM 2002) and consolidation with radioimmunotherapy following CHOP chemotherapy have all been shown to improve the outcome of DLBCL. We report the results of a Phase II clinical trial designed to evaluate the safety and efficacy of combination of the above, using 2-weekly CHOP+Rituximab followed by consolidation with Zevalin in patients with untreated DLBCL. Patients and Methods: Patients with previously untreated DLBCL with measurable disease, age>18 years and performance status 0-2 were eligible. Patients were required to have adequate marrow, liver and kidney functions. Patients with transformed lymphoma were excluded. Patients received standard CHOP along with Rituximab 375mg/m2 IV on day 1. Treatment was repeated every two weeks for a total of 6 cycles. Zevalin was administered within 6–8 weeks after the last dose of CHOPR therapy. Results: 14 patients were enrolled. The median age was 59.5 years (range 48–82), and 6 patients were men. All patients had an ECOG performance status of 0 or 1. 3 (21%) had stage II, 5 (36%) stage III and 6 (43%) had stage IV disease. IPI was 2 in 13 (93%) and 3 in 1 (7%). Bone marrow showed lymphoma in two patients only. LDH was elevated in 9 patients. All patients except 2 completed all 6 cycles of CHOP+R. One patient withdrew consent after 5 cycles and one patient with multiple lung masses could not be continued on therapy after two cycles because of prolonged rehab. Following CHOP+R alone in patients who received a minimum of 4 cycles of CHOP+R (13), 8 patients achieved CR and 5 achieved PR. Following consolidation with Zevalin, three patients in PR were converted to CR. After a median follow-up of 17.5 months, OSS is 14/14 (100%). 11 patients (79%) remain in CR. One patient progressed and proceeded to stem cell transplant; one came off study after 2 cycles of CHOP+R and remains with evidence of disease; and the third patient, who achieved PR with CHOP+R is waiting restaging after Zevalin. Most common adverse events were hematologic. Grade 3 Neutropenia was observed in 10 patients and grade 4 in 7. Grade 3 thrombocytopenia was observed in 3 and grade 4 in 1. Non-hematologic toxicities included: grade 3 pneumonia in 3, DVT in 1, grade 4 pneumonia in 1, grade 3 fever in 2 and grade 4 fever in 1. Conclusion: Consolidation with Zevalin radioimmunotherapy following dose dense CHOP+R therapy is well tolerated, effective and able to convert PRs to CRs.
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Voorhees, Peter M., Robert F. Manges, Pieter Sonneveld, Sundar Jagannath, George Somlo, Amrita Krishnan, Suzanne Lentzsch, et al. "A Phase 2 Multicenter Study of Siltuximab, An Anti-IL-6 Monoclonal Antibody, in Patients with Relapsed or Refractory Multiple Myeloma,." Blood 118, no. 21 (November 18, 2011): 3971. http://dx.doi.org/10.1182/blood.v118.21.3971.3971.
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Abstract Abstract 3971 Background: Although outcomes have improved for patients (pts) with multiple myeloma (MM), relapsed/refractory MM remains associated with short survival and constitutes an unmet medical need. Glucocorticoids (GCs) are an important component of MM therapy; however, resistance is common. In preclinical models, interleukin-6 (IL-6) promotes the proliferation and survival of MM cells in the context of the bone marrow microenvironment and protects these cells from GC-induced apoptosis. Therefore, blocking IL-6 may disrupt resistance and restore sensitivity to GCs. Here, we report the final results from a Phase 2 open-label, non-randomized study that evaluated the safety and efficacy of siltuximab (S), a monoclonal antibody targeting soluble human IL-6, in combination with high-dose dexamethasone (D) in pts with relapsed and relapsed/refractory MM. Methods: Pts with measurable, secretory disease who had received at least 2 prior lines of therapy, one of which contained bortezomib, and progressed during or after their last line of treatment were eligible. Other key eligibility criteria included a creatinine clearance ≥20 mL/min, platelets ≥50,000/mm3, and neutrophils ≥1,000/mm3. S was administered 6 mg/kg IV on days 1 and 15 of a 28-day cycle and oral D 40mg once daily, on days 1–4, 9–12, and 17–20 for a max of 4 cycles; days 1–4 for subsequent cycles. The first 14 pts received S alone for the initial 1 to 2 cycles; 10 pts had D added for progressive disease post-Cycle 1 or suboptimal response post-Cycle 2. 39 subsequent pts received S+D concurrently as none of the first 14 pts achieved ≥PR while on S monotherapy. The primary endpoint was overall response rate (ORR, CR+PR) using EBMT criteria. Secondary endpoints were time to progression (TTP), progression-free survival (PFS), overall survival (OS), and incidence of AEs and SAEs. Results: Forty-nine pts received S+D. The median age was 65 yrs (range 43–89) and 43% of pts were female. The median disease duration was 4 yrs (range 0.7–13.2). Pts were heavily pretreated, having received prior bortezomib (100%), steroids (100%), IMIDs (90%), alkylating agents (91%) and ASCT (65%). The median number of prior lines of therapy was 4 (range 2–9); 86% had disease that was refractory to the last prior line. Of the 44 pts with prior D exposure, 32 (73%) were refractory to the last D-containing regimen. The median duration of therapy was 4 cycles (99 days). Of the 47 pts evaluable for response, the ORR by EBMT criteria was 17% (0 CRs, 8 PRs); the ORR + minimal response (MR) rate was 23.4% (N=11). Using IMWG criteria, the ORR + MR rate was 27.7% (9 PRs, 4 MRs). Of the 11 pts with at least MR by EBMT criteria, 5 pts were refractory to the last D-containing regimen and 7 experienced less than MR on a prior D-containing regimen. The median duration of response was 5.9 months (181 days, 95% CI: 147, 365). Three pts had a long-lasting response of 9 months or more. For all 49 pts, the median PFS was 3.7 months (114 days, 95% CI: 84, 148) and median OS was 20.4 months (621 days, 95% CI: 347,984). AEs occurring in ≥25% of pts were thrombocytopenia, fatigue, anemia, abnormal hepatic function, neutropenia, diarrhea, peripheral edema, dyspnea and dizziness. 74% of pts experienced a grade ≥3 AE; the most frequent non-hematologic grade ≥3 AEs were fatigue (8%), abnormal hepatic function (8%), and pneumonia (6%). Grade 4 hematologic toxicities were thrombocytopenia (12%), neutropenia (4%) and anemia (2%). 25% of pts discontinued treatment due to an AE. Twenty (41%) of the 49 pts experienced ≥1 SAE. The most frequently occurring SAEs were pneumonia (8%), thrombocytopenia (6%), septic shock, anemia, and hemolytic anemia (4% each). Five pts died during the study; 3 due to progressive disease, 2 due to infection (nosocomial infection, septic shock). Conclusions: The combination of siltuximab with dexamethasone was well tolerated. Although the ORR was modest in this relapsed/refractory patient population, responses were seen in pts with MM refractory to prior dexamethasone-containing therapy, suggesting that siltuximab may be able to at least partially overcome dexamethasone resistance in some cases. Overall, these results provide a rationale for further studies of siltuximab in combination with dexamethasone-based MM therapy. Disclosures: Voorhees: MedImmune: Consultancy; Pfizer: Research Funding; Centocor Ortho Biotech: Research Funding; Celgene: Research Funding; Merck: Research Funding. Off Label Use: Siltuximab for the treatment of multiple myeloma. Manges:Centocor Ortho Biotech: Research Funding. Sonneveld:Millennium Pharmaceuticals: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Onyx: Consultancy, Research Funding. Jagannath:Merck: Honoraria; Millennium Pharmaceuticals: Honoraria; Johnson and Johnson Pharmaceuticals: Consultancy; Celgene: Consultancy, Honoraria; Centocor Ortho Biotech: Research Funding. Somlo:Onyx: Consultancy; Millennium: Consultancy; Celgene: Consultancy, Speakers Bureau; Centocor Ortho Biotech: Research Funding. Krishnan:Celgene: Speakers Bureau; Millennium Pharmaceuticals: Speakers Bureau; Centocor Ortho Biotech: Research Funding. Lentzsch:Celgene: Consultancy, Research Funding; Onyx: Consultancy; Genzyme: Consultancy; Centocor Ortho Biotech: Research Funding. Frank:Centocor Ortho Biotech: Research Funding. Zweegman:Centocor Ortho Biotech: Research Funding. Wijermans:Centocor Ortho Biotech Research & Development: Research Funding. Rijnbeek:Ortho Biotech Oncology Research and Development: Employment. Qin:Johnson & Johnson Pharmaceutical Research & Development, LLC: Employment. Cornfeld:Ortho Biotech Oncology Research and Development: Employment. Xie:Ortho Biotech Oncology Research & Development: Employment. Thomas:Centocor Ortho Biotech: Research Funding; Millennium Pharmaceuticals: Research Funding; Celgene: Research Funding; Novartis: Research Funding; Immunomedics: Research Funding.