Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor recognition by ROR 1-specific CARs 1 Receptor affinity and extracellular domain modifications affect tumor recognition by ROR 1-specific chimeric antigen receptor T-cells

Purpose: The adoptive transfer of T-cells modified to express a chimeric antigen receptor (CAR) comprised of an extracellular single chain antibody (scFV) fragment specific for a tumor cell surface molecule, and linked to an intracellular signaling module has activity in advanced malignancies. ROR1 is a tumor-associated molecule expressed on prevalent B-lymphoid and Research. on June 3, 2017. © 2013 American Association for Cancer clincancerres.aacrjournals. org Downloaded from Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on April 25, 2013; DOI: 10.1158/1078-0432.CCR-13-0330
How Investors Face Financial Risk: Loss Aversion and Wealth Allocation

We study how the wealth-allocation decisions and the loss aversion of non-professional investors change subject to behavioral factors. The optimal wealth assignment between risky and risk-free assets results within a VaR portfolio model, where risk is individually assessed according to an extended prospect-theory framework. We show how the past performance and the portfolio evaluation frequency impact investor behavior. Myopic loss aversion holds at different evaluation frequencies. One year is the optimal frequency at which, under practical constraints, risky holdings are maximized. Previous research using standard VaR-significance levels may underestimate the loss aversion of individual investors.
DNA-protein interaction dynamics at the Lamin B2 replication origin

To date, a complete understanding of the molecular events leading to DNA replication origin activation in mammalian cells still remains elusive. In this work, we report the results of a high resolution chromatin immunoprecipitation study to detect proteins interacting with the human Lamin B2 replication origin. In addition to the pre-RC component ORC4 and to the transcription factors USF and HOXC13, we found that 2 components of the AP-1 transcription factor, c-Fos and c-Jun, are also associated with the origin DNA during the late G1 phase of the cell cycle and that these factors interact with ORC4. Both DNA replication and AP-1 factor binding to the origin region were perturbed by cell treatment with merbarone, a topoisomerase II inhibitor, suggesting that DNA topology is essential for determining origin function.
Induction and Modulation of Hepatic Preneoplasia and Neoplasia in the Rat by Dehydroepiandrosterone

Dehydroepiandrosterone (DHEA), the main adrenal steroid in humans and a precursor in androgen and estrogen biosynthesis, acts as a peroxisome proliferator and as a hepatocarcinogen in rats. Neoplasms emerge from a glycogenotic/amphophilic/basophilic preneoplastic cell lineage. A higher female tumor incidence suggests a relevant influence of sex hormones. DHEA enhances hepatocarcinogenesis induced byN-nitrosomorpholine (NNM), which is characterized by the glycogenotic/basophilic cell lineage. The tumor promoting effect is related to an additional amphophilic/basophilic preneoplastic lesion sequence and to faster proliferation of the basophilic preneoplastic lesions. Nevertheless, hepatocellular carcinomas provided under DHEA treatment seem to have a less malignant phenotype compared to tumors induced by NNM only. Further, DHEA treatment reduces growth and generation of glycogen storage foci (GSF) in initial NNM-treated rats. Thus, DHEA treatment results in both, a growth stimulation of the late basophilic lesion type with an additional amphophilic lesion sequence, and in a growth inhibition of early preneoplastic lesions, addressing especially GSF. DHEA also inhibits the growth of physiologically proliferating liver tissue. This might be explained by a DHEA related cellular metabolism, which results in significant energy consumption. Additionally, a DHEA-induced alteration of cytokine levels might contribute to this growth inhibition as well.
Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate

ABSTRACT Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are the first and second leading viral agents of severe respiratory tract disease in infants and young children worldwide. Vaccines are not available, and an RSV vaccine is particularly needed. A live attenuated chimeric recombinant bovine/human PIV3 (rB/HPIV3) vector expressing the RSV fusion (F) glycoprotein from an added gene has been under development as a bivalent vaccine against RSV and HPIV3. Previous clinical evaluation of this vaccine candidate suggested that increased genetic stability and immunogenicity of the RSV F insert were needed. This was investigated in the present study. RSV F expression was enhanced 5-fold by codon optimization and by modifying the amino acid sequence to be identical to that of an early passage of the original clinical isolate. This conferred a hypofusogenic phenotype that presumably reflects the original isolate. We then compared vectors expressing stabilized prefusion and postfusion versions of RSV F. In a hamster model, prefusion F induced increased quantity and quality of RSV-neutralizing serum antibodies and increased protection against wild-type (wt) RSV challenge. In contrast, a vector expressing the postfusion F was less immunogenic and protective. The genetic stability of the RSV F insert was high and was not affected by enhanced expression or the prefusion or postfusion conformation of RSV F. These studies provide an improved version of the previously well-tolerated rB/HPIV3-RSV F vaccine candidate that induces a superior RSV-neutralizing serum antibody response. IMPORTANCE Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are two major causes of pediatric pneumonia and bronchiolitis. The rB/HPIV3 vector expressing RSV F protein is a candidate bivalent live vaccine against HPIV3 and RSV. Previous clinical evaluation indicated the need to increase the immunogenicity and genetic stability of the RSV F insert. Here, we increased RSV F expression by codon optimization and by modifying the RSV F amino acid sequence to conform to that of an early passage of the original isolate. This resulted in a hypofusogenic phenotype, which likely represents the original phenotype before adaptation to cell culture. We also included stabilized versions of prefusion and postfusion RSV F protein. Prefusion RSV F induced a larger quantity and higher quality of RSV-neutralizing serum antibodies and was highly protective. This provides an improved candidate for further clinical evaluation.
Los Antecedentes de la Capacidad de Absorción: Análisis Crítico y Proposición de un Modelo de Integración

Este articulo contiene una revision de la literatura relacionada con los antecedentes de la capacidad de absorcion publicada hasta la fecha. En el se destacan los aportes mas relevantes que se han hecho sobre el tema. Ademas, se describen las principales fortalezas alcanzadas y las debilidades aun existentes en la materia. Para hacer frente a una de las principales carencias encontradas, el articulo propone un modelo que permite reconocer y ordenar los antecedentes identifi cados en la literatura; percibir el nivel de abstraccion en que han sido enunciados; comprender las relaciones fundamentales entre ellos y advertir la precedencia en que deben ser obtenidos. Lo anterior, observando el caracter acumulativo de la capacidad de absorcion en dos dimensiones, el nivel organizativo y el tipo de capacidad de absorcion y de conocimiento.
Thy‐1 positive tingible body macrophages (TBM) in mouse lymph nodes

This study was prompted by the observation that cells in mouse lymph nodes (LN) with cytological characteristics of tingible body macrophages (TBM) appeared to be Thy‐1 positive. The objective of this study was to determine if these large cells were TBM and to conclusively demonstrate their reactivity for Thy‐1. The cells were studied using monoclonal antibodies (MoAb) against Thy‐1 and macrophage markers including F4/80 and Ia antigens at both light microscopic (LM) and electron microscopic (EM) levels. Immunocytochemical reactivity by TBM for Thy‐1 antigen specific MoAb was demonstrated by LM in both in situ and in vitro LN preparations. Furthermore, ultrastructural examination of these germinal center cells in situ demonstrated that the Thy‐1 reactivity visualized at the LM level was associated with ribosomes and endoplasmic reticulum as well as their plasma membrane. Similarly, these cells expressed intracytoplasmic and membrane reactivity for Ia antigens and also for the macrophage specific antigen F4/80. This indicates that the reactivity is due to active synthesis of the Thy‐1 antigen and not attributable to reactivity of any phagocytosed Thy‐1 positive cells. As defined by their germinal center location and morphological characteristics, these Thy‐1 reactive macrophages were identified as TBM. Germinal center TBM thus represent a unique, vigorously phagocytic subset of mature macrophages which express both macrophage and thymocyte markers.
Evaluation of Aintree LOSS, a community‐based, multidisciplinary weight management service: outcomes and predictors of engagement

Aintree LOSS is a community‐based, multidisciplinary weight management programme for patients with severe and complex obesity, focusing on a flexible and individualized service with follow‐up for up to 2 years. We evaluated all 2472 patients referred to the service between October 2009 and 2013. Demographic data were recorded at baseline, with the Index of Multiple Deprivation (IMD) used to measure socioeconomic deprivation. Weight was recorded at each visit. Mean body mass index at baseline was 45.6 (standard deviation 6.8), and 58.9% of patients lived in areas in the most deprived decile nationally. Of 2315 appropriate referrals, 1249 (55.1%) attended >2 visits; mean final weight loss was 3.50 ± 8.55 kg, and 24.1% achieved ≥5% weight loss. Of the patients, 754 (33.3%) attended for over 6 months; mean final weight loss was 4.94 ± 10 kg, and 34% achieved 5% weight loss. Multivariate logistic regression analysis showed increasing age, residence in a less deprived area and sleep apnoea to be independently associated with attendance for >6 months, and there was a linear relationship between 6‐month attendance and deprivation quintile. Year‐on‐year analyses showed improvement in engagement over time, coinciding with efforts to improve access to the service. This work shows a multidisciplinary, community‐based weight loss programme prioritizing a fully flexible and individualized approach functioning effectively in real‐world practice. Maintaining engagement remains a challenge in weight loss programmes, and our results suggest younger patients living in areas with greater deprivation should be a target for efforts to improve engagement.
Middle East respiratory syndrome coronavirus in children

The Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). The disease is reported mainly in adults. Data in children are scarce. The disease caused by MERS-CoV in children presents with a wide range of clinical manifestations, and it is associated with a lower mortality rate compared with adults. Poor outcome is observed mainly in admitted patients with medical comorbidities. We report a new case of MERS-CoV infection in a 9-month-old child complicated by severe respiratory symptoms, multi-organ dysfunction, and death. We reviewed the literature in an attempt to characterize the mode of presentation, the risk factors, and outcome of MERS-CoV infection in the pediatric population.
Income Redistribution Predicts Greater Life Satisfaction Across Individual, National, and Cultural Characteristics

The widening income gap between the rich and the poor has important social implications. Governmental-level income redistribution through tax and welfare policies presents an opportunity to reduce income inequality and its negative consequences. The current longitudinal studies examined whether within-region changes in income redistribution over time relate to life satisfaction. Moreover, I examined potential moderators of this relationship to test the strong versus weak hypotheses of income redistribution. The strong hypothesis posits that income redistribution is beneficial to most. The weak hypothesis posits that income redistribution is beneficial to some and damaging to others. Using a nationally representative sample of 57,932 German respondents from 16 German states across 30 years (Study 1) and a sample of 112,876 respondents from 33 countries across 24 years (Study 2), I found that within-state and within-nation changes in income redistribution over time were associated with life satisfaction. The models predicted that a 10% reduction in Gini through income redistribution in Germany increased life satisfaction to the same extent as an 37% increase in annual income (Study 1), and a 5% reduction in Gini through income redistribution increased life satisfaction to the same extent as a 11% increase in GDP (Study 2). These associations were positive across individual, national, and cultural characteristics. Increases in income redistribution predicted greater satisfaction for tax-payers and welfare-receivers, for liberals and conservatives, and for the poor and the rich. These findings support the strong hypothesis of income redistribution and suggest that redistribution policies may play an important role in societal well-being.
The pgdA Gene Encodes for a PeptidoglycanN-Acetylglucosamine Deacetylase in Streptococcus pneumoniae *

Analytical work on the fractionation of the glycan strands of Streptococcus pneumoniae cell wall has led to the observation that an unusually high proportion of hexosamine units (over 80% of the glucosamine and 10% of the muramic acid residues) was not N-acetylated, explaining the resistance of the peptidoglycan to the hydrolytic action of lysozyme, a muramidase that cleaves in the glycan backbone. A gene, pgdA, was identified as encoding for the peptidoglycanN-acetylglucosamine deacetylaseA with amino acid sequence similarity to fungal chitin deacetylases and rhizobial NodB chitooligosaccharide deacetylases. Pneumococci in which pgdA was inactivated by insertion duplication mutagenesis produced fully N-acetylated glycan and became hypersensitive to exogenous lysozyme in the stationary phase of growth. The pgdA gene may contribute to pneumococcal virulence by providing protection against host lysozyme, which is known to accumulate in high concentrations at infection sites.
Interactions between the L1 cell adhesion molecule and ezrin support traction‐force generation and can be regulated by tyrosine phosphorylation

An Ig superfamily cell‐adhesion molecule, L1, forms an adhesion complex at the cell membrane containing both signaling molecules and cytoskeletal proteins. This complex mediates the transduction of extracellular signals and generates actin‐mediated traction forces, both of which support axon outgrowth. The L1 cytoplasmic region binds ezrin, an adapter protein that interacts with the actin cytoskeleton. In this study, we analyzed L1–ezrin interactions in detail, assessed their role in generating traction forces by L1, and identified potential regulatory mechanisms controlling ezrin–L1 interactions. The FERM domain of ezrin binds to the juxtamembrane region of L1, demonstrated by yeast two‐hybrid interaction traps and protein binding analyses in vitro. A lysine‐to‐leucine substitution in this domain of L1 (K1147L) shows reduced binding to the ezrin FERM domain. Additionally, in ND7 cells, the K1147L mutation inhibits retrograde movement of L1 on the cell surface that has been linked to the generation of the traction forces necessary for axon growth. A membrane‐permeable peptide consisting of the juxtamembrane region of L1 that can disrupt endogenous L1–ezrin interactions inhibits neurite extension of cerebellar cells on L1 substrates. Moreover, the L1–ezrin interactions can be modulated by tyrosine phosphorylation of the L1 cytoplasmic region, namely, Y1151, possibly through Src‐family kinases. Replacement of this tyrosine together with Y1176 with either aspartate or phenylalanine changes ezrin binding and alters colocalization with ezrin in ND7 cells. Collectively, these data suggest that L1–ezrin interactions mediated by the L1 juxtamembrane region are involved in traction‐force generation and can be regulated by the phosphorylation of L1. © 2008 Wiley‐Liss, Inc.
PURIFICATION AND EVIDENCE FOR THE INVOLVEMENT OF TRYPTOPHAN RESIDUE AT THE CATALYTIC SITE OF B FRUCTOFURANOSIDASE FROM A THERMOTOLERANT YEAST KLUYVEROMYCES MARXIANUS NCYC 2675

β Fructofuranosidase from Kluyveromyces. marxianus NCYC 2675 was purified using hydrophobic interaction chromatography.The purified enzyme had specific activity of 2116 3moles/min/ml. Molecular weight was determined by gel filtration and SDSPAGE. This was further confirmed by MALDITOF. The protein was found to be a non glycosylated monomer of molecular mass 67 kDa and exhibited a pI of 3.7. Effects of amino acid specific modifying agents were studied to determine the amino acid residue at the catalytic site. NBS and HNBBr, chemical modifiers of tryptophan showed concentration and time dependant linear inactivation of the enzyme. Modification with 60 =M of NBS and 40 mM of HNBBr resulted in 75% and 70% inactivation respectively. Substrate sucrose, and the products glucose and fructose, significantly lowered the extent of inactivation by the tryptophan modifying reagents. The reactions followed pseudo firsto rder kinetics and the inactivation kinetics indicated the presence of a single tryptophan residue near or at the catalytic site .
A Novel Design of Microstrip Diplexer Using Meander-Line Resonators

In this paper, a compact microstrip diplexer is proposed for Wimax and DCS applications at 2.5 GHz and 1710-1880 MHz respectively. The microstrip diplexer consists of two band-pass filters operating at different frequency bands and a coupledjunction. Each filter is formed by a meander-line resonator and two Input/Output feed lines. The frequency response of each filter can be easily controlled by modifying the dimensions of the meander-line resonators. ADS and CST-MWS solvers have been used to characterize the response of the diplexer. Good electrical performances are obtained after an optimization of the proposed circuit. The microstrip diplexer presents an insertion loss of 2.3 dB a return loss of 30 dB and an isolation between the two filters better than 22 dB for an overall size of 25×32 mm 2 .
Coal miners exposed to diesel exhaust emissions.

Abstract The possibility of adverse respiratory health effects amongst coal miners in and at diesel-use mines has been investigated. Coal miners working in and at non-diesel-use mines served as matched controls. Differences in symptom prevalence and pulmonary function performance are documented. Several health indices have been related to a measure of diesel exposure. A preliminary characterization of the underground environment is shown. Underground miners in diesel-use mines reported more symptoms of cough and phlegm and had generally lower pulmonary function performance than matched controls. Similar trends were noted for surface workers at diesel-use mines compared with matched controls. Although a pattern consistent with small airways disease is shown, factors other than diesel exposure may be responsible. Exposure time to diesel emissions for miners in this study is relatively short and measured concentrations are low. Based on present information, sufficient and consistent evidence does not exist allowing for the rejection of hypotheses of health equality between matched groups. A prudent public health stance dictates reservation of judgment pending prospective examinations and detailed environmental surveys.
Ligament strain on the iliofemoral, pubofemoral, and ischiofemoral ligaments in cadaver specimens: Biomechanical measurement and anatomical observation

The iliofemoral, pubofemoral, and ischiofemoral ligaments are major structures that stabilize the hip joint. We have sought evidence on which to base more effective hip stretching positions. The purpose of this study was to measure strains on these ligaments and to observe them. Eight fresh/frozen translumbar cadaver specimens were used. Clinically available stretching positions for these ligaments were adopted. Strain on each ligament was measured by a displacement sensor during passive torque to the hip joint. Hip motion was measured using an electromagnetic tracking device. The strained ligaments were captured on clear photographs. Significantly, high strains were imposed on the superior iliofemoral ligament by external rotation of the hip (3.48%); on the inferior iliofemoral ligament by maximal extension and 10° or 20° of external rotation with maximal extension (1.86%, 1.46%, 1.25%); on the pubofemoral ligament by maximal abduction and 10°, 20°, or 30° of external rotation with maximal abduction (3.18%, 3.28%, 3.11%, 2.99%); and on the ischiofemoral ligament by 10° or 20° of abduction with maximal internal rotation (7.11%, 7.83%). Fiber direction in each ligament was clearly identified. Significantly, high strains on hip ligaments corresponded with the anatomical direction of the ligament fibers. Positions were identified for each ligament that imposed maximal increase in strain on it. Clin. Anat. 27:1068–1075, 2014. © 2014 Wiley Periodicals, Inc.
Evidence of Bose-Einstein Condensation in an Atomic Gas with Attractive Interactions.

Evidence for Bose-Einstein condensation of a gas of spin-polarized {sup 7}Li atoms is reported. Atoms confined to a permanent-magnet trap are laser cooled to 200 {mu}K and are then evaporatively cooled to lower temperatures. Phase-space densities consistent with quantum degeneracy are measured for temperatures in the range of 100 to 400 nK. At these high phase-space densities, diffraction of a probe laser beam is observed. Modeling shows that this diffraction is a sensitive indicator of the presence of a spatially localized condensate. Although measurements of the number of condensate atoms have not been performed, the measured phase-space densities are consistent with a majority of the atoms being in the condensate, for total trap numbers as high as 2{times}10{sup 5} atoms. For {sup 7}Li, the spin-triplet {ital s}-wave scattering length is known to be negative, corresponding to an attractive interatomic interaction. Previously, Bose-Einstein condensation was predicted not to occur in such a system.
“Shocking” Masculinity: Stanley Milgram, “Obedience to Authority,” and the “Crisis of Manhood” in Cold War America

Stanley Milgram's study of “obedience to authority” is one of the best-known psychological experiments of the twentieth century. This essay examines the study's special charisma through a detailed consideration of the intellectual, cultural, and gender contexts of Cold War America. It suggests that Milgram presented not a “timeless” experiment on “human nature” but, rather, a historically contingent, scientifically sanctioned “performance” of American masculinity at a time of heightened male anxiety. The essay argues that this gendered context invested the obedience experiments with an extraordinary plausibility, immediacy, and relevance. Immersed in a discourse of masculinity besieged, many Americans read the obedience experiments not as a fanciful study of laboratory brutality but as confirmation of their worst fears. Milgram's extraordinary success thus lay not in his “discovery” of the fragility of individual conscience but in his theatrical flair for staging culturally relevant masculine performances.