Miracle-dz/UniFAR-FTUs huggingface dataset:
A human scFv antibody that targets and neutralizes high molecular weight pathogenic amyloid‐β oligomers

Brain accumulation of soluble oligomers of the amyloid‐β peptide (AβOs) is increasingly considered a key early event in the pathogenesis of Alzheimer's disease (AD). A variety of AβO species have been identified, both in vitro and in vivo, ranging from dimers to 24mers and higher order oligomers. However, there is no consensus in the literature regarding which AβO species are most germane to AD pathogenesis. Antibodies capable of specifically recognizing defined subpopulations of AβOs would be a valuable asset in the identification, isolation, and characterization of AD‐relevant AβO species. Here, we report the characterization of a human single chain antibody fragment (scFv) denoted NUsc1, one of a number of scFvs we have identified that stringently distinguish AβOs from both monomeric and fibrillar Aβ. NUsc1 readily detected AβOs previously bound to dendrites in cultured hippocampal neurons. In addition, NUsc1 blocked AβO binding and reduced AβO‐induced neuronal oxidative stress and tau hyperphosphorylation in cultured neurons. NUsc1 further distinguished brain extracts from AD‐transgenic mice from wild type (WT) mice, and detected endogenous AβOs in fixed AD brain tissue and AD brain extracts. Biochemical analyses indicated that NUsc1 targets a subpopulation of AβOs with apparent molecular mass greater than 50 kDa. Results indicate that NUsc1 targets a particular AβO species relevant to AD pathogenesis, and suggest that NUsc1 may constitute an effective tool for AD diagnostics and therapeutics.
Is the WKL1 gene associated with schizophrenia?

A missense mutation Leu309Met in the WKL1 (MLC1, KIAA0027) gene, mapped to 22q13.3, was reported to co‐segregate with periodic catatonic schizophrenia (SCZ) in a single large German pedigree with seven affected individuals (Meyer et al. [2001: Mol Psychiatry 6:302–306]). This report raised the following questions that were dealt with in the present study: does the Leu309Met mutation have a role in SCZ, or only in catatonic SCZ? Does the mutation Leu309Met in the WKL1 gene, encoding a putative membrane protein, non‐selective cation channel, have any effect on the channel activity? Is the WKL1 gene, which is expressed exclusively in brain, expressed differently in SCZ brains compared to controls? These questions were answered by screening the Leu309Met mutation in 117 Israeli Jewish patients with SCZ (55 Ashkenazi and 62 non‐Ashkenazi Jews) and 176 matched controls. In search of differences in the level of WKL1 gene expression, postmortem dorsalateral prefrontal cortex of 16 schizophrenic patients and 15 controls was checked. We also measured the putative channel activity of normal WKL1 subcloned in pcDNA3 to determine the effect of the reported Leu309Met mutation. Our results argue against the involvement of WKL1 in SCZ susceptibility. © 2003 Wiley‐Liss, Inc.
Variable prediction accuracy of polygenic scores within an ancestry group

Fields as diverse as human genetics and sociology are increasingly using polygenic scores based on genome-wide association studies (GWAS) for phenotypic prediction. However, recent work has shown that polygenic scores have limited portability across groups of different genetic ancestries, restricting the contexts in which they can be used reliably and potentially creating serious inequities in future clinical applications. Using the UK Biobank data, we demonstrate that even within a single ancestry group, the prediction accuracy of polygenic scores depends on characteristics such as the age or sex composition of the individuals in which the GWAS and the prediction were conducted, and on the GWAS study design. Our findings highlight both the complexities of interpreting polygenic scores and underappreciated obstacles to their broad use.
Sexual Harassment as a Gendered Expression of Power

Drawing on recent insights from the study of legal consciousness and gender relations, the authors test the generality of Catharine MacKinnon's theory of the sexual harassment of adult women. Survey and interview data from the Youth Development Study and the General Social Survey are analyzed to identify a behavioral syndrome of sexual harassment for males and females during adolescence and young adulthood and to compare the syndrome against subjective reports of sexual harassment. A clear harassment syndrome is found for all age and sex groups and MacKinnon's predictions about the influence of workplace power and gender relations are generally supported. Financially vulnerable men as well as women are most likely to experience harassing behaviors, and men pursuing more egalitarian gender relationships are most likely to identify such behaviors as sexual harassment. Nevertheless, adult women remain the most frequent targets of classic sexual harassment markers, such as unwanted touching and invasion of personal space.
Macrolide maintenance treatment for bronchiectasis

Bronchiectasis, pathological widening of the small and medium sized bronchi, may result from various disorders with one common trait; a faltering airway defence system. This allows for persistent bacterial infection and an augmented airway inflammatory response. Patients’ suffering is often considerable and is characterized by a chronic, productive cough and intermittent infectious exacerbations. In case of failure of non-pharmaceutical treatment options, bronchiectasis patients with frequent exacerbations have frequently been treated with long term, low dose antibiotic treatment, more specifically, the macrolide antibiotic azithromycin. This medical practice has not been based on solid evidence to confirm the efficacy of macrolide maintenance treatment and surprisingly little was known about the potential downsides of this treatment modality. In this thesis, we provide an overview of the current knowledge on bronchiectasis, its diagnostic challenges and the available treatment options. A structured clinical workup is advocated, for which a diagnostic flow chart is offered. We investigate efficacy and safety of macrolide maintenance treatment in a randomised controlled trial, describe radiological responses to treatment and some of azithromycin’s pharmacokinetic properties. We conclude by expressing our concerns on indiscriminate use of azithromycin maintenance treatment, because of its important downsides; the induction of microbial resistance, besides other detrimental effects. Ideally, azithromycin maintenance treatment should be reserved for a ‘macrolide-responsive’ phenotype of bronchiectasis patients and in this thesis we give directions for further research in this area by proposing patient characteristics which might be predictive for a beneficial response to this treatment modality.
Pit2 Assemblies at the Cell Surface Are Modulated by Extracellular Inorganic Phosphate Concentration

ABSTRACT Pit2 is a type III sodium-dependent phosphate transporter and the cell surface receptor for amphotropic murine leukemia virus. Indirect arguments have previously suggested that retrovirus receptor assembly play a role in triggering membrane fusion. Using CHO cells expressing physiological amounts of functional versions of human Pit2 fused to various tagging epitopes, we provide evidence that Pit2 forms assemblies at the cell surface. Living cells were exposed to cross-linking reagents and protein extracts were treated with trifluoroacetic acid (TFA), a chemical that destroys all protein interactions but covalent links. Assemblies were also detected in the absence of cross-linking and TFA treatment, indicating that they are partially resistant to detergent denaturation. The formation of homo-oligomers was documented by the coimmunoprecipitation of differently tagged molecules. The amounts of Pit2 assemblies detected in the presence or in the absence of cross-linking reagents varied with extracellular inorganic phosphate concentration ([Pi]). Variation of signal intensity was in the range of twofold, occurred in the absence of de novo protein synthesis and took place at the cell surface. These results indicate that Pit2 assemblies exhibit variable conformations at the surface of living cells. Susceptibility to virus infection and phosphate uptake also vary with extracellular [Pi]. A model is proposed in which cell surface Pit2 assemblies switch from a compacted to an expanded configuration in response to changes of extracellular [Pi], and possible relationships with the variation of biological activities are discussed.
Ensembling Factored Neural Machine Translation Models for Automatic Post-Editing and Quality Estimation

This work presents a novel approach to Automatic Post-Editing (APE) and Word-Level Quality Estimation (QE) using ensembles of specialized Neural Machine Translation (NMT) systems. Word-level features that have proven effective for QE are included as input factors, expanding the representation of the original source and the machine translation hypothesis, which are used to generate an automatically post-edited hypothesis. We train a suite of NMT models that use different input representations, but share the same output space. These models are then ensembled together, and tuned for both the APE and the QE task. We thus attempt to connect the state-of-the-art approaches to APE and QE within a single framework. Our models achieve state-of-the-art results in both tasks, with the only difference in the tuning step which learns weights for each component of the ensemble.
Insights into the CtrA regulon in development of stress resistance in obligatory intracellular pathogen Ehrlichia chaffeensis

Ehrlichia chaffeensis is an obligate intracellular bacterium that causes human monocytic ehrlichiosis. Ehrlichiae have a biphasic developmental cycle consisting of dense‐cored cells (DCs) and reticulate cells (RCs). Isolated DCs are more stress resistant and infectious than RCs. Here, we report that a response regulator, CtrA was upregulated in human monocytes at the late growth stage when DCs develop. E. chaffeensis CtrA bound to the promoters of late‐stage transcribed genes: ctrA, ompA (peptidoglycan‐associated lipoprotein), bolA (stress‐induced morphogen) and surE (stationary‐phase survival protein), which contain CtrA‐binding motifs, and transactivated ompA, surE and bolA promoter–lacZ fusions in Escherichia coli. OmpA was predominantly expressed in DCs. E. chaffeensis binding to and subsequent infection of monocytes were inhibited by anti‐OmpA IgG. E. chaffeensis BolA bound to the promoters of genes encoding outer surface proteins TRP120 and ECH_1038, which were expressed in DCs, and transactivated trp120 and ECH_1038 promoter–lacZ fusions. E. chaffeensis bolA complemented a stress‐sensitive E. coli bolA mutant. E. coli expressing E. chaffeensis SurE exhibited increased resistance to osmotic stress. Our results suggest that E. chaffeensis CtrA plays a role in co‐ordinating development of the stress resistance for passage from the present to the next host cells through its regulon.
Alpha-Fetoprotein

Alpha-fetoprotein (AFP) is a circulating glycopro tein that is a major component of embryonic and fetal serum that decreases to nearly undetectable amounts near the time of birth. Serum levels of AFP do not increase in adults except under three distinct conditions: pregnancy, liver injury and carcinoma (hepatic or certain germ cell tumors). During preg nancy, maternal serum and amniotic fluid levels of AFP may be abnormal in a wide variety of fetal abnormalities and pregnancy complications. Meas urement of AFP in adults has evolved into two dis tinct clinical roles: as a tumor marker for hepatic and germ cell carcinoma, and as a screen for abnormal pregnancies
Applicability of the Dyes CFSE, CM-DiI and PKH26 for Tracking of Human Preadipocytes to Evaluate Adipose Tissue Engineering

Adipose tissue engineering with preadipocyte-loaded scaffolds requires adequate tracking of preadipocytes to allow evaluation and quantification of cell proliferation, expansion and differentiation in three-dimensional systems. To differentiate between graft and host cells, labeling of preadipocytes before implantation and tracking of these cells until harvest would be useful. Immunohistochemistry enables the differentiation between cells of different species but is time-consuming, expensive, elaborate, and not applicable for autologous transplantation. So far, there is no published method to use externally applied dyes for tracking of human preadipocytes in adipose tissue engineering. We tested the cell dyes PKH26, CM-DiI, and CFSE to analyze their applicability for labeling human preadipocytes. CM-DiI had toxicity levels of 45–70%, while 3–4% proliferating cells were stained on day 35. CFSE revealed clear cytoplasmic coloring in proliferating cells with 5–6% stained cells after 35 days and toxicity ranging from 55 to 90% dead cells. PKH26 demonstrates lowest levels of toxicity and best labeling results after 4 weeks in proliferating preadipocytes in monolayer. Although none of the dyes showed long-lasting labeling during proliferation, all three dyes demonstrated permanent staining in differentiated cells. The results reveal the problems of preadipocyte tracking with fluorescent dyes but justify the dye application for limited time periods.
The Impact of Biometeorological Conditions on the Perception of Landscape

A landscape is part of our daily lives and our perception of its features may significantly impact our quality of life. This article presents the results of research aimed at determining the influence of biometeorological conditions on the way in which we perceive the landscape. An eye tracker was used throughout each season of the year to determine how 52 respondents observed the landscape while taking into consideration whether the landscape had a favorable or unfavorable impact on those same respondents. Additionally, each test was preceded by the completion of a questionnaire intended to assess the mental and physical state of each respondent. The calculated eye movement indexes demonstrated the impact of the biometeorological conditions on their perception of the landscape. Statistically significant differences in their perception of the landscape were ascertained depending on the type of weather and the respondents’ general feeling irrespective of their sex.
Advances in Brief A p 53-independent Pathway for Induction of p 21 w & IflciPland Concomitant G , Arrest in UV-irradiated Human Skin Fibroblasts '

Largely on the basis of studies using the potent clastogen ionizing radiation, it has been widely assumed that up-regulation of the cydin dependent kinase inhibitor p2l@'@' in cultured cells exposed to DNA damaging agents is contingent upon the presence of functional p53 tumor suppressor protein. Nevertheless, we demonstrate here that the model mutagen 254-nm UV light induces p21'@Â°@ protein and concomitant G1 arrest in normal human skin fibroblasts, as well as in p53-deficient fibroblasts derived from cancer-prone Li-Fraumeni syndrome patients. However, as expected, following exposure to ionizing radiation, elevated @21wafl@@1@ protein levels and G1 arrest were observed only in normal fibroblasts. These data provide a prominent and clinically relevant exam pIe in which p215va@@l.mediatedgrowth arrest occurs independently of p53 in human cells treated with a model DNA-damaging agent.
Topological Insulator: $\hbox{Bi}_{2}\hbox{Te}_{3}$  Saturable Absorber for the Passive Q-Switching Operation of an in-Band Pumped 1645-nm Er:YAG Ceramic Laser

An in-band pumped 1.645-μm Er:YAG ceramic laser passively Q-switched by a topological insulator: Bi<sub>2</sub>Te<sub>3</sub> saturable absorber is reported. The average output power could reach up to 210 mW, corresponding to a pulsewidth, a pulse repetition rate, and a per-pulse energy of 6.3 μs, 40.7 kHz, and 5.3 μJ, respectively. This result indicates that the topological insulator: Bi<sub>2</sub>Te<sub>3</sub> could be a promising saturable absorber such as graphene, with potential applications for solid-state lasers.
Early stalked stages in ontogeny of the living isocrinid sea lily Metacrinus rotundus

The early stalked stages of an isocrinid sea lily, Metacrinus rotundus, were examined up to the early pentacrinoid stage. Larvae induced to settle on bivalve shells and cultured in the laboratory developed into late cystideans. Three-dimensional (3D) images reconstructed from very early to middle cystideans indicated that 15 radial podia composed of five triplets form synchronously from the crescent-shaped hydrocoel. The orientation of the hydrocoel indicated that the settled postlarvae lean posteriorly. In very early cystideans, the orals, radials, basals and infrabasals, with five plates each in the crown, about five columnals in the stalk, and five terminal stem plates in the attachment disc, had already formed. In mid-cystideans, an anal plate appeared in the crown. Late cystideans cultured in the field developed into pentacrinoids about 5 months after settlement. These pentacrinoids shared many crown structures with adult sea lilies. On the other hand, many features of the stalk differed from those in adult isocrinids, while sharing many characteristics with the stalk of feather star pentacrinoids, including disc-like proximal columnals, high and slender median columnals, synarthrial articulations developmentally derived from the symplexial articulations, limited formation of cirri only in the proximal columnal(s), and an attachment disc. On the basis of these findings, phylogenetic relationships among extant crinoid orders are discussed.
The Use of Propensity Scores for Nonrandomized Designs With Clustered Data

In this article we propose several modeling choices to extend propensity score analysis to clustered data. We describe different possible model specifications for estimation of the propensity score: single-level model, fixed effects model, and two random effects models. We also consider both conditioning within clusters and conditioning across clusters. We examine the underlying assumptions of these modeling choices and the type of randomized experiment approximated by each approach. Using a simulation study, we compare the relative performance of these modeling and conditioning choices in reducing bias due to confounding variables at both the person and cluster levels. An applied example based on a study by Hughes, Chen, Thoemmes, and Kwok (2010) is provided in which the effect of retention in Grade 1 on passing an achievement test in Grade 3 is evaluated. We find that models that consider the clustered nature of the data both in estimation of the propensity score and conditioning on the propensity score performed best in our simulation study; however, other modeling choices also performed well. The applied example illustrates practical limitations of these models when cluster sizes are small.
Genetic exchange of determinants for capsular polysaccharide biosynthesis between Klebsiella pneumoniae strains expressing serotypes K2 and K21a

The production of a capsular polysaccharide (CPS; K antigen) is characteristic of Klebsiella pneumoniae, but CPS structure varies among strains, and many different serotypes are now known. In this study, cps gene clusters encoding the elements of capsular polysaccharide biosynthesis were exchanged by homologous recombination between strains expressing different serotypes. The wild-type K. pneumoniae strains used for genetic exchange were KPA1 (cpsK2), expressing K2 CPS, and KPB1 (cpsK21a), expressing K21a CPS. Plasmid R68.45 was used to mobilize fragments of chromosomal DNA from auxotrophic derivatives of donor strains. Auxotrophic his alleles introduced into recipient strains provided selectable markers to coinherit the adjacent cps gene clusters from donors expressing a heterologous CPS. Each of the capsule-switched recombinants, KPA5 (cpsK21a) and KPB20 (cpsK2), was shown to have a CPS that was immunologically identical to the serotype of the respective donor. The recombinants retained their respective recipient strain background, as evidenced by a genetic marker and demonstration of a distinctive restriction fragment length polymorphism in genomic DNA. KPB1 CPS contained a sequence (mannose-alpha-2-mannose) that binds to a macrophage lectin and may be responsible for their higher susceptibility to macrophage binding and phagocytosis compared with KPA1, whose CPS lacked such sequences. The recombinant strains expressing heterologous cps genes inherited the macrophage-binding phenotype of the donor, thus confirming that relative susceptibility to phagocytosis was determined by the capsule type expressed. KPA1 was highly virulent in a mouse lethality assay, which is a feature typical of K2 strains, whereas KPB1 was not virulent in mice. Recombinant KPA5 retained relatively high virulence in mice, even though it produced the heterologous K21a CPS, which suggests that a virulence factor other than capsule biosynthesis is encoded by the KPA genomic strain background. In contrast, KPB20 gained marginal virulence in the mouse lethality assay through the inheritance and expression of the K2 CPS from the virulent strain. Thus, pathogenesis in K. pneumoniae may be multifactorial. Specific antibody was used to stabilize the CPS on the surface of K. pneumoniae, and the structural organization of the homologous and heterologous capsules was examined by electron microscopy. Recombinant KPB20, expressing heterologous K2 CPS, had a uniform layer of capsule surrounding the organism that was similar to that seen on the surfaces of the parental strains. However, KPA5, expressing the heterologous K21a CPS, was unusual in that the uniform capsular layer was physically separated from the cell wall by approximately 50 nm. (ABSTRACT TRUNCATED AT 400 WORDS)
Incidence of Spontaneous Resorption of Lumbar Disc Herniation: A Meta-Analysis.

BACKGROUND Lumbar disc herniation (LDH), a common disease, is often treated conservatively, frequently resulting in spontaneous resorption of the herniated disc. The incidence of this phenomenon, however, remains unknown. OBJECTIVE To analyze the incidence of spontaneous resorption after conservative treatment of LDH using computed tomography and magnetic resonance imaging. STUDY DESIGN Meta-analysis and systematic review of cohort studies. SETTING The work was performed at The Suzhou Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine. METHODS We initiated a search for the period from January 1990 to December 2015 using PubMed, Embase, and the Cochrane Library. Two independent reviewers examined the relevant reports. The references from these reports were also searched for additional trials using the criteria established in the PRISMA statement. RESULTS Our results represent the pooled results from 11 cohort studies. The overall incidence of spontaneous resorption after LDH was 66.66% (95% CI 51% - 69%). The incidence in the United Kingdom was 82.94% (95% CI 63.77% - 102.11%). The incidence in Japan was 62.58% (95% CI 55.71% - 69.46%). LIMITATIONS Our study was limited because there were few sources from which to extract data, either in abstracts or published studies. There were no randomized, controlled trials that met our criteria. CONCLUSIONS The phenomenon of LDH reabsorption is well recognized. Because its overall incidence is now 66.66% according to our results, conservative treatment may become the first choice of treatment for LDH. More large-scale, double-blinded, randomized, controlled trials are necessary to study the phenomenon of spontaneous resorption of LDH.Key words: Lumbar, disc herniation, spontaneous resorption, conservative treatment, incidence, country, meta-analysis, systematic review, observational studies, study designs.