Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling and Simulation of Aggregation of Membrane Protein LAT with Molecular Variability in the Number of Binding Sites for Cytosolic Grb 2-SOS 1-Grb 2

The linker for activation of T cells (LAT), the linker for activation of B cells (LAB), and the linker for activation of X cells (LAX) form a family of transmembrane adaptor proteins widely expressed in lymphocytes. These scaffolding proteins have multiple binding motifs that, when phosphorylated, bind the SH2 domain of the cytosolic adaptor Grb2. Thus, the valence of LAT, LAB and LAX for Grb2 is variable, depending on the strength of receptor activation that initiates phosphorylation. During signaling, the LAT population will exhibit a time-varying distribution of Grb2 valences from zero to three. In the cytosol, Grb2 forms 1:1 and 2:1 complexes with the guanine nucleotide exchange factor SOS1. The 2:1 complex can bridge two LAT molecules when each Grb2, through their SH2 domains, binds to a phosphorylated site on a separate LAT. In T cells and mast cells, after receptor engagement, receptor phosphoyrlation is rapidly followed by LAT phosphorylation and aggregation. In mast cells, aggregates containing more than one hundred LAT molecules have been detected. Previously we considered a homogeneous population of trivalent LAT molecules and showed that for a range of Grb2, SOS1 and LAT concentrations, an equilibrium theory for LAT aggregation predicts the formation of a gel-like phase comprising a very large aggregate (superaggregate). We now extend this theory to investigate the effects of a distribution of Grb2 valence in the LAT population on the formation of LAT aggregates and superaggregate and use stochastic simulations to calculate the fraction of the total LAT population in the superaggregate. Citation: Nag A, Monine M, Perelson AS, Goldstein B (2012) Modeling and Simulation of Aggregation of Membrane Protein LAT with Molecular Variability in the Number of Binding Sites for Cytosolic Grb2-SOS1-Grb2. PLoS ONE 7(3): e28758. doi:10.1371/journal.pone. 0028758 Editor: Thomas Höfer, German Cancer Research Center, Germany Received July 20, 2011; Accepted November 14, 2011; Published March 1, 2012 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Funding: This work was supported by the Department of Energy through contract W-7405-ENG-36, and National Institutes of Health grants R37-GM035556 (BG), R37-AI028433 (ASP), R01-RR006555 (ASP) and P01-AI071195 (ASP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: ambarish.nag@nrel.gov ¤a Current address: Computational Sciences Center, National Renewable Energy Laboratory, Golden, Colorado, United States of America ¤b Current address: Novartis Institutes for Biomedical Research, Inc., Cambridge, Massachusetts, United States of America
A Classification of Cardiac Allograft Rejection: A Modification of the Classification by Billingham

We herein propose a classification of rejection in cardiac allografts based on the original Stanford work. Our modified classification, as a work hypothesis, defines the following grades: (a) mild acute rejection (A-l), corresponding to Billingham's “mild rejection”; (b) mild acute rejection with probable conversion to moderate rejection (A-2); (c) moderate acute rejection (A-3), comparable to Billingham's “moderate rejection”; and (d) severe acute rejection (A-4), morphologically identical with the respective grade in the Billingham classification. The resolution of rejection has been classified into two grades— early (A-5a) and late (A-5b) resolution—according to the development of granulation tissues. We also grade the degree of vasculopathy (B-l, B-2) and chronic rejection (C), which is characterized by aggressive fibrosis and persistent vasculopathy. Mild rejection with possible conversion to moderate rejection is defined by an increasing quantity of retrogressive changes in myocytes. Changes not related to transplantation are characterized in our classification by descriptive diagnosis. The proposed classification was validated by 1 year of clinical experience and by the evaluation of possible prognostic aspects of the classification.
INFLUÊNCIA DA MINERALOGIA NA COMPOSIÇÃO QUÍMICA DE METAIS PESADOS NOS SEDIMENTOS PELÍTICOS SUPERFICIAIS DA PLATAFORMA CONTINENTAL DO AMAZONAS

This study was carried out in the Amazon Continental Shelf bottom sediments, along the mouth of the Pará river (PA) and the Orange cape (AP). By using of stoichiometric calculations, chemical analyses and X-ray diffraction data, the results allowed to evidence the kaolinite and illite domains in the most of the samples and some quartz and carbonate. The occurrence of heavy metals (Fe, Mn, Ti, Cr, Co, Ni) and Zn was investigated by use of chemical and Pearson linear correlations analyses. Significant correlations for Al and heavy metals show associations involving geochemical phases; for Ca, the correlations data confirm occurrence of carbonate.
Craniovertebral junction anomalies: When is resurgery required?

BACKGROUND Craniovertebral junction (CVJ) abnormalities, such as atlantoaxial dislocation (AAD) with or without basilar invagination (BI), with or without associated Chiari malformation (CM), may cause a high cervical myelopathy. Occasionally, mechanical factors such as inadequate canal decompression, torticollis, and/or scoliosis may lead to lack of improvement following the primary surgery. Furthermore, implant-related factors, requiring implant revision/removal, or the presence of surgical site infections may cause the patient to undergo resurgery. AIMS This study was aimed at highlighting the underlying etiopathogenesis of resurgery following the primary surgery undertaken in CVJ abnormalities. SETTING AND DESIGN This was a retrospective study from a tertiary care referral institute focusing on 414 operated cases of CVJ anomalies. MATERIALS AND METHODS The data of 55 patients who underwent resurgery included their clinicoradiological assessment and operative records. The inclusion criteria included failed primary procedure, repeat procedure for construct failure, infection at the surgical site, or wound dehiscence. Pure CM patients without bony anomalies were excluded from the study. RESULTS A total of 137 procedures were performed in 55/414 (13%) patients. Causes of resurgery could be divided into ventral [redo or denovo transoral decompression (TOD) or wound-related complications, n = 33, 40.2%] and dorsal causes (implant-related factors/wound infections, n = 49, 59.8%). De novo TOD was done in persisting myelopathy following posterior fusion (PF) with C1-2 distraction (n = 15,18.3%,). Redo TOD was done for residual anterior bony compression [n = 8, 9.6%, OR 0.61; [CI = 0.20-1.86]. Causes for oral wound reexplorations (n = 10, 12.2%) included velopharyngeal insufficiency, wound resuturing, oral bleeding, and cerebrospinal fluid (CSF) leak. Dorsal causes included: (A) Implant factors (n = 27, 32.7%) and (B) neck wound reexplorations (n = 22, 26.8%). Presence of subaxial spine scoliosis, torticollis, and asymmetric joints increased the incidence of reexploration. Occipitocervical fusion rather than C1-2 fusion was more prone towards construct loosening. CONCLUSIONS Patients undergoing distraction with PF may require transoral surgery due to persisting myelopathy, especially in the presence of torticollis, scoliosis, and symmetrical joints. Single stage TOD+PF increases the chances of implant infection due to tissue contamination, bacteremia, or transfacetal migration of microbes. Chronic/recurrent sinus is usually a harbinger of deeper infection and can be cured with implant removal.
Approaching Single-Hop Performance in Multi-Hop Networks: End-To-End Known-Interference Cancellation (E2E-KIC) - Long Version

To improve the efficiency of wireless data communications, new physical-layer transmission methods based on known-interference cancellation (KIC) have been developed. These methods share the common idea that the interference can be cancelled when the content of it is known. Existing work on KIC mainly focuses on single-hop or two-hop networks, with physical-layer network coding (PNC) and full-duplex (FD) communications as typical examples. This paper extends the idea of KIC to general multi-hop networks, and proposes an end-to-end KIC (E2E-KIC) transmission method together with its MAC design. With E2E-KIC, multiple nodes in a flow passing through a few nodes in an arbitrary topology can simultaneously transmit and receive on the same channel. We first present a theoretical analysis on the effectiveness of E2E-KIC in an idealized case. Then, to support E2E-KIC in multi-hop networks with arbitrary topology, we propose an E2E-KIC-supported MAC protocol (E2E-KIC MAC), which is based on an extension of the Request-to-Send/Clear-to-Send (RTS/CTS) mechanism in the IEEE 802.11 MAC. We also analytically analyze the performance of the proposed E2E-KIC MAC in the presence of
Human Monoclonal Antibody to Hepatitis C Virus E1 Glycoprotein That Blocks Virus Attachment and Viral Infectivity

ABSTRACT Human antibodies elicited in response to hepatitis C virus (HCV) infection are anticipated to react with the native conformation of the viral envelope structure. Isolation of these antibodies as human monoclonal antibodies that block virus binding and entry will be useful in providing potential therapeutic reagents and for vaccine development. H-111, an antibody to HCV envelope 1 protein (E1) that maps to the YEVRNVSGVYH sequence and is located near the N terminus of E1 and is able to immunoprecipitate E1E2 heterodimers, is described. Binding of H-111 to HCV E1 genotypes 1a, 1b, 2b, and 3a indicates that the H-111 epitope is highly conserved. Sequence analysis of antibody V regions showed evidence of somatic and affinity maturation of H-111. Finally, H-111 blocks HCV-like particle binding to and HCV virion infection of target cells, suggesting the involvement of this epitope in virus binding and entry.
Translocation of capsular polysaccharides in pathogenic strains of Escherichia coli requires a 60-kilodalton periplasmic protein

An 11.6-kilobase (kb) region of a 34-kb fragment of Escherichia coli DNA that encodes the K1 capsular polysaccharide genes is necessary for translocation of the K1 polysaccharide to the bacterial cell surface. This 11.6-kb region contains a gene, kpsD, encoding a 60-kilodalton protein. The kpsD gene was localized to a 2.4-kb PstI-BamHI fragment. Cells harboring a Tn1000 insertion in kpsD did not synthesize the 60-kilodalton protein and did not express polysaccharide on the cell surface. Immunodiffusion and rocket immunoelectrophoresis of cell extracts, however, demonstrated that K1 polysaccharide was synthesized by these cells. We present evidence that the kpsD gene product is synthesized as a precursor and that the processed form is located in the periplasmic space. Analysis of alkaline phosphatase activity of a kpsD-phoA fusion demonstrated that kpsD expression was under positive regulation. A 260-base-pair AluI fragment located within the kpsD coding sequence was used as a probe and was found to hybridize to chromosomal DNA from E. coli that synthesizes the K2, K5, K7, K12, and K13 capsular polysaccharides but not K3 and K100. These results suggest that the kpsD gene product may be required for export not only of K1 but for other K antigens as well.
Early treatment of Campylobacter jejuni enteritis

The bacteriologic and clinical effects of early antibiotic treatment of Campylobacter jejuni enteritis were studied. Erythromycin rapidly eliminated C. jejuni from stools, whereas trimethoprim-sulfamethoxazole did not. Despite its bacteriologic effectiveness, erythromycin did not reduce the duration or severity of diarrhea, abdominal pain, or other symptoms.
Phase-shift control of isolated bidirectional DC-DC converters for unidirectional power flow

In the conventional phase-shift control of isolated bidirectional DC-DC converters, the phenomenon of power backflow is quite obvious. General improved phase-shift control methods can reduce the power backflow of the input. However, they do not take the power backflow of the output into consideration. In this paper, a novel phase-shift control of isolated bidirectional DC-DC converters for unidirectional power flow is proposed. It can eliminate the power backflows of both the input and the output at the same time. Furthermore, the converters in the proposed phase-shift control can achieve the zero-current switching in the whole power rang. Experimental results from a prototype verify the feasibility and validity of the proposed control method, and show superior performance.
Income distribution and mortality: cross sectional ecological study of the Robin Hood index in the United States

Abstract Objective: To determine the effect of income inequality as measured by the Robin Hood index and the Gini coefficient on all cause and cause specific mortality in the United States. Design: Cross sectional ecological study. Setting: Households in the United States. Main outcome measures: Disease specific mortality, income, household size, poverty, and smoking rates for each state. Results: The Robin Hood index was positively correlated with total mortality adjusted for age (r=0.54; P<0.05). This association remained after adjustment for poverty (P<0.007), where each percentage increase in the index was associated with an increase in the total mortality of 21.68 deaths per 100000. Effects of the index were also found for infant mortality (P=0.013); coronary heart disease (P=0.004); malignant neoplasms (P=0.023); and homicide (P<0.001). Strong associations were also found between the index and causes of death amenable to medical intervention. The Gini coefficient showed very little correlation with any of the causes of death. Conclusion: Variations between states in the inequality of income were associated with increased mortality from several causes. The size of the gap between the wealthy and less well off—as distinct from the absolute standard of living enjoyed by the poor—seems to matter in its own right. The findings suggest that policies that deal with the growing inequities in income distribution may have an important impact on the health of the population. Key messages The size of the gap between the wealthy and less well off—as distinct from the absolute standard of living enjoyed by the poor—seems to be related to mortality Policies that deal with the growing inequities in income distribution may have a considerable impact on the health of the population
Dynamic Integrated MPP Tracker in 0.35 μm CMOS

An integrated CMOS controller with fast maximum power point regulation for module-integrated automotive solar converters with nine solar cells per string is reported. It provides the 530-kHz switching signals for the module-integrated converter whereby the mean output current of the module is maximized. The on-chip “perturb and observe” algorithm bases on a quasi-analog principle and performs more than 1000 tracking cycles/s at a power consumption around 560 μW. In order to maximize the precision, the duration of the measurement intervals is automatically adjusted to the output current. Due to the use of a very small shunt resistance of 1 mΩ for the current measurement, the insertion loss is small and the circuit complexity is kept low. Between 0.25- and 5-A photocurrent, the tracker achieves a tracking efficiency better than 99.5%.
Fever detection & classroom temperature adjustment: Using infrared cameras

Classrooms or closed areas in general have a higher chance of transmitting viral and bacterial diseases such as flu or influenza. In this paper we are proposing a new system that will help to prevent the spread of a viral disease in classrooms at its early stage by keeping track of the students' body temperature. The system uses multiple infrared cameras that controls the room temperature and also detects students with a temperature higher than 37oC. Once the camera detects a student with a temperature higher than 37oC it sends a report to the school nurse to take immediate action. The system also adjusts the class room temperature according to the students' body temperature by averaging the students' body temperature.
Regulation of Vascular Endothelial Growth Factor Receptor 2-mediated Phosphorylation of Focal Adhesion Kinase by Heat Shock Protein 90 and Src Kinase Activities*

Exposure of endothelial cells to vascular endothelial growth factor (VEGF) induced tyrosine phosphorylation of focal adhesion kinase (FAK) on site Tyr407, an effect that required the association of VEGF receptor 2 (VEGFR2) with HSP90. The association of VEGFR2 with HSP90 involved the last 130 amino acids of VEGFR2 and was blocked by geldanamycin, a specific inhibitor of HSP90. Moreover, geldanamycin inhibited the VEGF-induced activation of the small GTPase RhoA, which resulted in an inhibition of phosphorylation of FAK on site Tyr407. In this context, the inhibition of RhoA kinase (ROCK) with Y27632 or by expression of dominant negative forms of RhoA or ROCK impaired the VEGF-induced phosphorylation of Tyr407 within FAK. In contrast to phosphorylation of Tyr861, the phosphorylation of site Tyr407 was insensitive to Src kinase inhibition by 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2). We also found that the recruitment of paxillin to FAK was inhibited by geldanamycin but not by PP2, whereas both geldanamycin and PP2 inhibited the recruitment of vinculin to FAK. In accordance, the recruitment of paxillin and vinculin to FAK was inhibited in cells that express the mutant FAK-Y407F, whereas the expression of the mutant Y861F inhibited the recruitment of paxillin but not of vinculin. Importantly, cell migration was abolished in cells in which the signal from the VEGFR2-HSP90 pathway was blocked by the expression of Δ130VEGFR2, a deletant of VEGFR2 that does not associate with HSP90. Our findings underscore for the first time the key role played by the VEGFR2-HSP90-RhoA-ROCK-FAK/Tyr407 pathway in transducing the VEGF signal that leads to the assembly of focal adhesions and endothelial cell migration.
Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations

ABSTRACT Introduction: Hematopoietic cell transplantation for Fanconi Anemia (FA) has improved dramatically over the past 40 years. With an enhanced understanding of the intrinsic DNA-repair defect and pathophysiology of hematopoietic failure and leukemogenesis, sequential changes to conditioning and graft engineering have significantly improved the expectation of survival after allogeneic hematopoietic cell transplantation (alloHCT) with incidence of graft failure decreased from 35% to <10% and acute graft-versus-host disease (GVHD) from >40% to <10%. Today, five-year overall survival exceeds 90% in younger FA patients with bone marrow failure but remains about 50% in those with hematologic malignancy. Areas covered: We review the evolution of alloHCT contributing to decreased rates of transplant related complications; highlight current challenges including poorer outcomes in cases of clonal hematologic disorders, alloHCT impact on endocrine function and intrinsic FA risk of epithelial malignancies; and describe investigational therapies for prevention and treatment of the hematologic manifestations of FA. Expert commentary: Current methods allow for excellent survival following alloHCT for FA associated BMF irrespective of donor hematopoietic cell source. Alternative curative approaches, such as gene therapy, are being explored to eliminate the risks of GVHD and minimize therapy-related adverse effects.
Changing Hormone Levels during the Menstrual Cycle Affect Knee Laxity and Stiffness in Healthy Female Subjects

Background Whether knee laxity varies throughout the menstrual cycle remains controversial. As increased laxity may be a risk factor for anterior cruciate ligament (ACL) injury, further research is warranted. Hypothesis Variation in estradiol and progesterone levels during the menstrual cycle influences knee laxity and stiffness. Study Design Case control study; Level of evidence, 3. Methods The serum estradiol and progesterone levels of 26 healthy female subjects were recorded in the follicular phase, ovulation, and the luteal phase. Knee joint laxity was assessed using a standard knee arthrometer at the same intervals. Stiffness changes in the load-displacement curve were determined. Hormone levels across the cycle were compared between responders and nonresponders, defined by whether changes in knee laxity at 89 N occurred. Results Greater laxity at 89 N during ovulation was observed (ovulation: 5.13 ± 1.70 mm vs luteal: 4.55 ± 1.54 mm, P =. 012). In knee laxity testing at manual maximum load, greater laxity was noticed during ovulation (14.43 ± 2.60 mm, P =. 018), as compared with the follicular phase (13.35 ± 2.53 mm). A reduction in knee stiffness of approximately 17% (ovulation: 12.48 ± 5.46 N/mm vs luteal: 15.02 ± 7.71 N/mm, P =. 042) during ovulation was observed. However, there were no differences in hormone levels between responders and nonresponders at 89 N. Conclusion Female hormone levels are related to increased knee joint laxity and decreased stiffness at ovulation. To understand subject variations in knee joint laxity during the menstrual cycle in female athletes, further investigation is warranted.
Quality characteristics of raw and cooked spent hen Pectoralis major muscles during chilled storage : Effect of salt and phosphate

Quality characteristics of spent hen Pectoralis major muscles and effect of NaCl and sodium tripolyphosphate (STPP) on quality changes of raw and cooked spent hen muscles during chilled storage were investigated. Meat from spent hen had nutritional values the same as commercial broiler meat. Treated raw samples with 1.0% NaCl and 10% STPP showed lower drip loss during storage time (P<0.05), and lower cooking loss (P<0.05) at day 6 and day 9 of storage compared with untreated samples. However, weight loss of cookeduntreated samples exhibited lower (P<0.05) than did in cooked-treated samples as storage time increased. NaCl and STPP had more effective to reduce TBARS values and extend shelf-life of cooked samples than did in raw samples during chilled storage. There were no significant differences on other chemical and physical properties of raw and cooked spent hens all storage time, demonstrating the ineffectiveness of NaCl and STPP.