Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of Antigenicity and Topology of E2 Glycoprotein Present on Recombinant Hepatitis C Virus-Like Particles

ABSTRACT Purification of hepatitis C virus (HCV) from sera of infected patients has proven elusive, hampering efforts to perform structure-function analysis of the viral components. Recombinant forms of the viral glycoproteins have been used instead for functional studies, but uncertainty exists as to whether they closely mimic the virion proteins. Here, we used HCV virus-like particles (VLPs) generated in insect cells infected with a recombinant baculovirus expressing viral structural proteins. Electron microscopic analysis revealed a population of pleomorphic VLPs that were at least partially enveloped with bilayer membranes and had viral glycoprotein spikes protruding from the surface. Immunogold labeling using specific monoclonal antibodies (MAbs) demonstrated these protrusions to be the E1 and E2 glycoproteins. A panel of anti-E2 MAbs was used to probe the surface topology of E2 on the VLPs and to compare the antigenicity of the VLPs with that of truncated E2 (E2660) or the full-length (FL) E1E2 complex expressed in mammalian cells. While most MAbs bound to all forms of antigen, a number of others showed striking differences in their abilities to recognize the various E2 forms. All MAbs directed against hypervariable region 1 (HVR-1) recognized both native and denatured E2660 with comparable affinities, but most bound either weakly or not at all to the FL E1E2 complex or to VLPs. HVR-1 on VLPs was accessible to these MAbs only after denaturation. Importantly, a subset of MAbs specific for amino acids 464 to 475 and 524 to 535 recognized E2660 but not VLPs or FL E1E2 complex. The antigenic differences between E2660, FL E1E2, and VLPs strongly point to the existence of structural differences, which may have functional relevance. Trypsin treatment of VLPs removed the N-terminal part of E2, resulting in a 42-kDa fragment. In the presence of detergent, this was further reduced to a trypsin-resistant 25-kDa fragment, which could be useful for structural studies.
Different but Equal: Total Work, Gender and Social Norms in EU and US Time Use

Overall, the issue of whether Europeans are lazy or Americans are crazy seems of second-order importance relative to understanding the determinants of individual behavior. Amore useful, scientific approach is to assume that underlying tastes are common to both continents, while technologies, institutions, or interpersonal influences like norms or externalities may differ and evolve differently. The fact that Americans work on weekends or more often at odd hours of the day may simply represent a bad equilibrium that no individual agent can improve upon--and would certainly not wish to deviate from, given what all others are doing. Especially if norms and other externalities are important, one should recognize that the invisible hand may lead agents to places like this.
Low expression of BMPRIB indicates poor prognosis of breast cancer and is insensitive to taxane-anthracycline chemotherapy

Bone morphogenetic protein receptor type IB (BMPRIB) is one osteogenesis factor, which function in breast cancer has been rarely explored until recently. In the clinical study presented here, involving a cohort of 368 invasive ductal carcinoma (IDC) patients, we identified that patients with low expression of BMPRIB exhibited poor prognosis, especially in the luminal B subtype. We also provided the first piece of evidence that low level of BMPRIB was a promoting factor for breast cancer patients to develop bone metastasis, but not lung, liver or brain. The first of its kind, we reported that patients with high expression of BMPRIB exhibited favorable prognosis by a retrospective analysis consisting of 168 patients treated with TE (taxane and anthracycline) regimens. And the patients with high expression of BMPRIB were more sensitive to TE regimens in the detection of 32 paired pre-neoadjuvant and post-neoadjuvant specimens. Overall, our study concluded that low expression of BMPRIB indicated poor prognosis of breast cancer and was insensitive to taxane-anthracycline chemotherapy. Our findings also lay a foundation to help clinicians improve identification of patients for TE regimens by BMPRIB in the era of precision medicine.
Poly(ethylene glycol)-Coated Hexadecylcyanoacrylate Nanospheres Display a Combined Effect for Brain Tumor Targeting

The aim of the present study was to evaluate the tumor accumulation of radiolabeled long-circulating poly(ethylene glycol) (PEG)-coated hexadecylcyanoacrylate nanospheres and non-PEG-coated hexadecylcyanoacrylate nanospheres (used as control), after intravenous injection in Fischer rats bearing intracerebrally well established 9L gliosarcoma. Both types of nanospheres showed an accumulation with a retention effect in the 9L tumor. However, long-circulating nanospheres concentrated 3.1 times higher in the gliosarcoma, compared with non-PEG-coated nanospheres. The tumor-to-brain ratio of pegylated nanospheres was found to be 11, which was in accordance with the ratios reported for other carriers tested for brain tumor targeting such as long-circulating liposomes or labels for magnetic resonance imaging. In addition, a 4- to 8-fold higher accumulation of the PEG-coated carriers was observed in normal brain regions, when compared with control nanospheres. Using a simplified pharmacokinetic model, two different mechanisms were proposed to explain this higher concentration of PEG-coated nanospheres in a tumoral brain. 1) in the 9L tumor, the preferential accumulation of pegylated nanospheres was attributable to their slower plasma clearance, relative to control nanospheres. Diffusion/convection was the proposed mechanism for extravasation of the nanospheres in the 9L interstitium, across the altered blood-brain barrier. 2) In addition, PEG-coated nanospheres displayed an affinity with the brain endothelial cells (normal brain region), which may not be considered as the result of a simple diffusion/convection process. The exact underlying mechanism of such affinity deserves further investigation, since it was observed to be as important as specific interactions described for immunoliposomes with the blood-brain barrier.
Discovering robust protein biomarkers for disease from relative expression reversals in 2‐D DIGE data.

This study assesses the ability of a novel family of machine learning algorithms to identify changes in relative protein expression levels, measured using 2‐D DIGE data, which support accurate class prediction. The analysis was done using a training set of 36 total cellular lysates comprised of six normal and three cancer biological replicates (the remaining are technical replicates) and a validation set of four normal and two cancer samples. Protein samples were separated by 2‐D DIGE and expression was quantified using DeCyder‐2D Differential Analysis Software. The relative expression reversal (RER) classifier correctly classified 9/9 training biological samples (p<0.022) as estimated using a modified version of leave one out cross validation and 6/6 validation samples. The classification rule involved comparison of expression levels for a single pair of protein spots, tropomyosin isoforms and α‐enolase, both of which have prior association as potential biomarkers in cancer. The data was also analyzed using algorithms similar to those found in the extended data analysis package of DeCyder software. We propose that by accounting for sources of within‐ and between‐gel variation, RER classifiers applied to 2‐D DIGE data provide a useful approach for identifying biomarkers that discriminate among protein samples of interest.
Phenotypic Characterization of Prostate Cancer LNCaP Cells Cultured within a Bioengineered Microenvironment

Biophysical and biochemical properties of the microenvironment regulate cellular responses such as growth, differentiation, morphogenesis and migration in normal and cancer cells. Since two-dimensional (2D) cultures lack the essential characteristics of the native cellular microenvironment, three-dimensional (3D) cultures have been developed to better mimic the natural extracellular matrix. To date, 3D culture systems have relied mostly on collagen and Matrigel™ hydrogels, allowing only limited control over matrix stiffness, proteolytic degradability, and ligand density. In contrast, bioengineered hydrogels allow us to independently tune and systematically investigate the influence of these parameters on cell growth and differentiation. In this study, polyethylene glycol (PEG) hydrogels, functionalized with the Arginine-glycine-aspartic acid (RGD) motifs, common cell-binding motifs in extracellular matrix proteins, and matrix metalloproteinase (MMP) cleavage sites, were characterized regarding their stiffness, diffusive properties, and ability to support growth of androgen-dependent LNCaP prostate cancer cells. We found that the mechanical properties modulated the growth kinetics of LNCaP cells in the PEG hydrogel. At culture periods of 28 days, LNCaP cells underwent morphogenic changes, forming tumor-like structures in 3D culture, with hypoxic and apoptotic cores. We further compared protein and gene expression levels between 3D and 2D cultures upon stimulation with the synthetic androgen R1881. Interestingly, the kinetics of R1881 stimulated androgen receptor (AR) nuclear translocation differed between 2D and 3D cultures when observed by immunofluorescent staining. Furthermore, microarray studies revealed that changes in expression levels of androgen responsive genes upon R1881 treatment differed greatly between 2D and 3D cultures. Taken together, culturing LNCaP cells in the tunable PEG hydrogels reveals differences in the cellular responses to androgen stimulation between the 2D and 3D environments. Therefore, we suggest that the presented 3D culture system represents a powerful tool for high throughput prostate cancer drug testing that recapitulates tumor microenvironment.
1 PAIR PROGRAMMING : PAIRING ALONE IS NOT ENOUGH Version 1

The current focus on lightweight software processes emphasizes improvements in productivity and quality when two programmers work closely during development. We examine the productivity of two-person teams tasked to work independently on module construction versus two-person teams tasked to work concurrently on module construction. Analysis of this comparison reveals that teams in which member work more independently are significantly more productive than tightly coupled teams. Pair programming and lightweight software processes need to incorporate approaches designed to counteract this phenomenon. ACM
The Type I Inositol 1,4,5-Trisphosphate Receptor Interacts with Protein 4.1N to Mediate Neurite Formation through Intracellular Ca2+ Waves

Ca2+ waves are an important mechanism for encoding Ca2+ signaling information, but the molecular basis for wave formation and how this regulates neuronal function is not entirely understood. Using nerve growth factor-differentiated PC12 cells as a model system, we investigated the interaction between the type I inositol 1,4,5-trisphosphate receptor (IP3R1) and the cytoskeletal linker, protein 4.1N, to examine the relationship between Ca2+ wave formation and neurite development. This was examined using RNAi and overexpressed dominant negative binding regions of each protein. Confocal microscopy was used to monitor neurite formation and Ca2+ waves. Knockdown of IP3R1 or 4.1N attenuated neurite formation, as did binding regions of IP3R1 and 4.1N, which colocalized with endogenous 4.1N and IP3R1, respectively. Upon stimulation with the IP3-producing agonist carbachol, both RNAi and dominant negative molecules shifted signaling events from waves to homogeneous patterns of Ca2+ release. These findings provide evidence that IP3R1 localization, via protein 4.1N, is necessary for Ca2+ wave formation, which in turn mediates neurite formation.
The M2 Muscarinic Receptor Mediates Contraction through Indirect Mechanisms in Mouse Urinary Bladder

We investigated the contractile role of M2 muscarinic receptors in mouse urinary bladder. When measured in the absence of other agents, contractions elicited to the muscarinic agonist oxotremorine-M exhibited properties consistent with that expected for an M3 response in urinary bladder from wild-type and M2 knockout (KO) mice. Evidence for a minor M2 receptor-mediated contraction was revealed by a comparison of responses in M3 knockout and M2/M3 double knockout mice. Treatment of wild-type and M2 knockout urinary bladder with N-2-chloroethyl-4-piperidinyl diphenylacetate (4-DAMP mustard) caused a large inhibition of the muscarinic contractile response. The residual contractions were much smaller in M2 knockout bladder compared with wild type, suggesting that M2 receptors rescue the muscarinic contractile response in wild-type bladder following inactivation of M3 receptors with 4-DAMP mustard. When measured in the presence of prostaglandin F2α and isoproterenol or forskolin, oxotremorine-M mediated a potent contractile response in urinary bladder from M3 KO mice. This response exhibited an M2 profile in competitive antagonism studies and was completely absent in M2/M3 KO mice. Following 4-DAMP mustard treatment, oxotremorine-M elicited a contractile response in wild-type urinary bladder in the presence of KCl and isoproterenol or forskolin, and this response was diminished in M2 KO mice. Our results show that the M2 receptor mediates contractions indirectly in the urinary bladder by enhancing M3 receptor-mediated contractions and inhibiting relaxation. We also show that it is difficult to detect M2 receptor function in competitive antagonism studies under conditions where a simultaneous activation of M2 and M3 receptors occurs.
Determining the Precise Cerebral Response to Acupuncture: An Improved fMRI Study

Background In acupuncture brain imaging trials, there are many non-acupuncture factors confounding the neuronal mapping. The modality of the placebo, subjects’ psychological attitude to acupuncture and their physical state are the three most confounding factors. Objective To obtain more precise and accurate cerebral fMRI mapping of acupuncture. Design and Setting A 2×2 randomized, controlled, participant-blinded cross-over factorial acupuncture trial was conducted at Xuanwu Hospital in Beijing, China. Participants Forty-one college students with myopia were recruited to participate in our study and were allocated randomly to four groups, Group A, Group B, Group C and Group D. Interventions Group A received real acupuncture (RA) and treatment instruction (TI); Group B received RA and non-treatment instruction (NI); Group C received sham acupuncture (SA) and TI; Group D received SA and NI. Results Stimulation at LR3 activated some areas of the visual cortex, and the cerebral response to non-acupuncture factors was complex and occurred in multiple areas. Conclusions The results provide more evidence regarding the credibility of acupuncture therapy and suggest that more precise experimental designs are needed to eliminate sources of bias in acupuncture controlled trials and to obtain sound results.
Coping with Imprisonment: Testing the Special Sensitivity Hypothesis for White-Collar Offenders

This study uses nationally representative prison data to test two competing theories of how white-collar offenders experience prison. The first perspective, referred to as the special sensitivity hypothesis, assumes that because of their social and demographic background characteristics white-collar offenders are more susceptible to the pains of imprisonment than other inmates. The second perspective, referred to as the special resiliency hypothesis, is based on the idea that these same background characteristics may reduce the pains of imprisonment for white-collar offenders. Ordinal and binary logistic regression models are used to estimate the effect of white-collar inmate status on several indicators of psychological adjustment. The current study finds partial support for the special resiliency hypothesis, but not the special sensitivity hypothesis. The results for each outcome are discussed regarding both theoretical and practical applications. The study’s limitations are also addressed and suggestions for future research on incarcerated white-collar offenders are given.
An ensemble learning based approach for building airfare forecast service

Modern airlines use sophisticated pricing models to maximize their revenue, which results in highly volatile airfares. Without sufficient information, it is usually difficult for ordinary customers to estimate future price changes. Over the last few years, several studies have tried to solve the problem of optimal purchase timing for flight tickets, in which the prediction task is described as a binary classification concerning to buy or wait at a given point. However, forecasting the real-time price changes has never received much attention from the research community. In this paper, we address the problem of airfare forecast and present a systematic approach that covers the most important aspects of building a forecast service, including data modelling, forecast algorithm and long-term prediction strategies. A novel matrix-like data schema is first introduced to organize price series and extract temporal features. For the prediction task, we specifically investigate Learn++. NSE, an incremental ensemble classifier designed for learning in nonstationary environments. We propose a modification of the original algorithm to make a regressor that is capable of learning incrementally from streaming price series, with an extra ability of multi-step ahead forecasting. We further evaluate the forecast model on real-world price data collected from diverse routes and discuss its performance with respect to short-term and long-term prediction.
Lithium: Implications for Neuropsychiatry and Wellness

Lithium is ubiquitous in the environment and probably an essential trace nutrient. The guidelines of major psychiatric association name lithium as a first-line therapy for bipolar disorder. Some studies have shown an association between low lithium intakes from water supplies and suicidality, as well as criminality. Other studies have shown that trace levels of lithium have neuroprotective abilities or improvements in mood and cognitive function. In animals, lithium upregulates neurotrophins, including brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3, as well as receptors to these growth factors in brain. Lithium has been reported to be beneficial in animal models of brain injury, stroke, amyotrophic lateral sclerosis, spinal cord injury, and degenerative diseases. A wide range of intracellular responses may be secondary to the inhibition of glycogen synthase kinase-3 beta and inositol monophosphatase by lithium. In humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of anti-apoptotic genes, inhibition of cellular oxidative stress, synthesis of brainderived neurotrophic factor, cortical thickening, increased grey matter density, and hippocampal enlargement. Many findings pose the question of whether the prospect of adding lithium to drinking water is realistic, weighing the benefits and potential risks. The bulk of evidence suggests that the optimum level of lithium intake is more than most people get from food and drinking water.
Some ergodic problems for differential games

We present a notion of ergodicity for deterministic zero-sum differential games that extends the one in classical ergodic control theory to systems with two conflicting controllers. We describe its connections with the existence of a constant and uniform long-time limit of the value function of finite horizon games, and characterize this property in terms of Hamilton-Jacobi-Isaacs equations. We also give several sufficient conditions for ergodicity and describe some extensions of the theory to stochastic differential games.
The Magnetic Landscape of the Sun's Polar Region

We present observations of the magnetic landscape of the polar region of the Sun that are unprecedented in terms of spatial resolution, field of view, and polarimetric precision. They were carried out with the Solar Optical Telescope aboard Hinode. Using a Milne-Eddington inversion, we find many vertically oriented magnetic flux tubes with field strengths as strong as 1 kG scattered in latitude between 70° and 90°. They all have the same polarity, consistent with the global polarity of the polar region. The field vectors are observed to diverge from the centers of the flux elements, consistent with a view of magnetic fields that are expanding and fanning out with height. The polar region is also found to have ubiquitous horizontal fields. The polar regions are the source of the fast solar wind, which is channeled along unipolar coronal magnetic fields whose photospheric source is evidently rooted in the strong-field, vertical patches of flux. We conjecture that vertical flux tubes with large expansion around the photospheric-coronal boundary serve as efficient chimneys for Alfvén waves that accelerate the solar wind.
Epidemiologic features of child unintentional injury in rural PuCheng, China

Abstract: Background: Epidemiologic features of unintentional injuries among children in rural China are unknown. Methods: Using a stratified sampling method, we conducted a retrospective study of injury reports over a year-long period. Structured oral questionnaires were administered to parents of 2551 children ages 0 to 14. Results: The annual incidence of unintentional injuries was 15.6%, with boys (16.7%) having a slightly higher rate than girls (14.5%; p greater than .05). The four leading causes of injury for both genders were falls (5.1% annual incidence), burns (2.9%), animal-related injuries (1.7%), and traffic injuries (1.6%). Conclusions: Unintentional injuries have substantial negative effects on children and their families. In rural PuCheng, China, the incidence of unintentional injury among children is extremely high compared to other regions of the world. The types of injuries incurred are somewhat different from those reported in other geographic areas. Injury prevention programs targeting the issues specific to this region, and similar rural regions of China, are needed.
Social reality makes the social mind

This paper contests social psychology’s emphasis on the biased, erroneous, and constructed nature of social cognition by: (1) showing how the extent of bias and error in classic research is overstated; (2) summarizing research regarding the accuracy of social beliefs; and (3) describing how social stereotypes sometimes improve person perception accuracy. A Goodness of Judgment Index is also presented to extract evidence regarding accuracy from research focusing on bias. We conclude that accuracy is necessary for understanding social cognition.
Alta prevalência de estresse em pós-graduandos de ciências veterinárias (High prevalence of stress in veterinary science post-graduate)

Stress is an unspecific physiological response in which the organism maintains homeostasis against stressor agents. The persistence of these agents may overcome the adaptation process, causing risks to ones heath. Graduate students are often submitted to stressful situations increasing their risk of presenting symptoms. The objective of this study was to evaluate stress prevalence in veterinary sciences graduate (master degree) students . The sample comprised 49 volunteers (26.14 ± 3,71 years of age), being 14 males (27,80 ± 5,03) and 35 women (26,84 ± 2,99) in all academic semesters. Lipp's Inventory of Stress Symptoms was employed in order to identify the predominant kind of symptom and the phase of development. The data analysis was performed by G test and Mann-Whitney (p<0,05). It was observed that stress symptoms were present in 75.51% of the volunteers especially at the resistance phase with predominance of psychological symptoms. It can be concluded that stress was very common among master degree students affecting both sexes similarly.