gebhart/patrepeval huggingface dataset:
High Y‐chromosomal Differentiation Among Ethnic Groups of Dir and Swat Districts, Pakistan (2017)

The ethnic groups that inhabit the mountainous Dir and Swat districts of northern Pakistan are marked by high levels of cultural and phenotypic diversity. To obtain knowledge of the extent of genetic diversity in this region, we investigated Y-chromosomal diversity in five population samples representing the three main ethnic groups residing within these districts, including Gujars, Pashtuns and Kohistanis. A total of 27 Y-chromosomal short tandem repeats (Y-STRs) and 331 Y-chromosomal single nucleotide polymorphisms (Y-SNPs) were investigated. In the Y-STRs, we observed very high and significant levels of genetic differentiation in nine of the 10 pairwise between-group comparisons (R<sub>ST</sub> 0.179-0.746), and the differences were mirrored in the Y-SNP haplogroup frequency distribution. No genetic differences were found between the two Pashtun subethnic groups Tarklanis and Yusafzais (R<sub>ST</sub> = 0.000). Utmankhels, also considered Pashtuns culturally, were not closely related to any of the other population samples (R<sub>ST</sub> 0.451-0.746). Thus, our findings provide examples of both associations and dissociations between cultural and genetic legacies. When analyzed within a larger continental-scale context, these five ethnic groups fall mostly outside the previously characterized Y-chromosomal gene pools of the Indo-Pakistani subcontinent. Male founder effects, coupled with culturally and topographically based constraints upon marriage and movement, are likely responsible for the high degree of genetic structure in this region.
Tryptophan scanning mutagenesis as a way to mimic the compound-bound state and probe the selectivity of allosteric inhibitors in cells (2020)

Understanding the selectivity of a small molecule for its target(s) in cells is an important goal in chemical biology and drug discovery. One powerful way to address this question is with dominant negative (DN) mutants, in which an active site residue in the putative target is mutated. While powerful, this approach is less straightforward for allosteric sites. Here, we introduce tryptophan scanning mutagenesis as an expansion of this idea. As a test case, we focused on the challenging drug target, heat shock cognate protein 70 (Hsc70), and its allosteric inhibitor JG-98. Structure-based modelling predicted that mutating Y149W in human Hsc70 or Y145W in the bacterial ortholog DnaK would place an indole side chain into the allosteric pocket normally occupied by the compound. Indeed, we found that the tryptophan mutants acted as if they were engaged with JG-98. We then used DnaK Y145W to suggest that this protein may be an anti-bacterial target. Indeed, we found that DnaK inhibitors have minimum inhibitory concentration (MIC) values <0.125 μg mL<sup>-1</sup> against several pathogens, including multidrug-resistant <i>Staphylococcus aureus</i> (MRSA) strains. We propose that tryptophan scanning mutagenesis may provide a distinct way to address the important problem of target engagement.
Optimized fluorescent labeling to identify memory B cells specific for <i>Neisseria meningitidis</i> serogroup B vaccine antigens <i>ex vivo</i> (2013)

Antigen-specific memory B cells generate anamnestic responses and high affinity antibodies upon re-exposure to pathogens. Attempts to isolate rare antigen-specific memory B cells for in-depth functional analysis at the single-cell level have been hindered by the lack of tools with adequate sensitivity. We applied two independent methods of protein labeling to sensitive and specific ex vivo identification of antigen-specific memory B cells by flow cytometry: stringently controlled amine labeling, and sortagging, a novel method whereby a single nucleophilic fluorochrome molecule is added onto an LPETG motif carried by the target protein. We show that sortagged NadA, a major antigen in the meningococcal serogroup B vaccine, identifies NadA-specific memory B cells with high sensitivity and specificity, comparable to NadA amine-labeled under stringent reaction parameters in a mouse model of vaccination. We distinguish NadA-specific switched MBC induced by vaccination from the background signal contributed by splenic transitional and marginal zone B cells. In conclusion, we demonstrate that protein structural data coupled with sortag technology allows the development of engineered antigens that are as sensitive and specific as conventional chemically labeled antigens in detecting rare MBC, and minimize the possibility of disrupting conformational B cell epitopes.
Autoimmune thyroiditis induced in mice depleted of particular T cell subsets. Characterization of thyroiditis-inducing T cell lines and clones derived from thyroid lesions (1993)

We have previously shown that autoimmune thyroiditis spontaneously develops in T cell-depleted (C57BL/6xC3H/He)F1 mice after adoptive transfer of syngeneic lymphoid cells that have been depleted of CD5bright T lymphocytes. This mouse model was considered to be an instructive model for Hashimoto's thyroiditis in humans, and suggested that CD5dull CD4+ autoreactive T cells are not deleted in normal lymphoid cell populations and induce thyroiditis after elimination of regulatory T cell subsets. In our study, we have established thyroid-derived T cell lines and clones by culturing thyroid-infiltrating lymphocytes with thyroid epithelial cells and syngeneic feeder cells in the presence of exogenous IL-2. Both CD4+ T cells and CD8+ T cells were identified and their CD5 expression was dull or negative. In our report, we focused on CD4+ T cells. Four CD4+ T cell lines and 19 clones were generated and characterized. CD4+ T cell clones derived from F1 hybrid (H-2b/k) mice responded to thyroid Ag in the context of not only class II MHC molecules from both parental strains (I-Ak or I-Ab), but also F1 unique MHC molecules. Thyroglobulin (Tg) was demonstrated to be a major autoantigen of the thyroid for T cell responses, and at least two epitopes of Tg were suggested to be recognized by T cell clones. An additional undefined thyroid component other than Tg was recognized by some T cell clones. Thyroid-derived T cells were all TCR-alpha beta+. Five types of V beta usage (V beta 2, 4, 8.3, 14, and an undefined V beta) were found in CD4+ T cells. Finally, the thyroid lesions could be transferred to syngeneic mice by five distinct groups of CD4+ T cell clones, which were distinguished on the basis of their Ag specificity, MHC restriction, and TCRV beta usage. The considerable heterogeneity of TCRV beta usage of thyroiditis-inducing T cell clones in this study may be attributed to the multiple patterns of their recognition of the thyroid autoantigens. These findings provide important implications for further understanding of organ-specific autoimmune processes induced by depletion of regulatory T cell subsets.
The TNO Vehicle Dynamics Database (VDD): a tool for comparision of vehicle dynamics behaviour (1996)

TNO has started a database containing data of vehicle dynamics properties of passenger cars, based on the results of eight objective ISO driving tests. From this database, car manufacturers and their suppliers can get the required information for design and marketing purposes in a fast and cost-saving manner. In close cooperation with the customer, the vehicles are chosen that will be tested. Every vehicle is submitted to a preparation programme, containing verification of manufacturers specifications with respect to wheel alignment, measurement of damper characteristics and mounting of new tyres. After the tests have been carried out and the data have been analysed, the results of the resuits will be presented in reports or in elecEonic format. TNO is also working on a presentation programme for the Database data, to create a helpful tool for analysis of vehicle handling performance. An example of working with the database is presented. Seven vehicles in the database are compared with respect to handling performance on crosswind sensitivity and lane change manoeuvre. The vehicles vary from small passenger cars to an MPV. The objective was not to compare vehicles in one class, but to demonstrate the use of a database in the design process.
On the Regiochemistry of Nucleophilic Attack on 2-Halo π-Allyl Complexes. 4. The Effect of Silver Acetate and Nucleophile Concentrations in Competitive Nucleophilic Attack with Malonate and Phenoxide Nucleophiles (2003)

2,3-Dibromo-1-propene or its allyl carbonate analogue are ionized under Pd catalysis to generate the 2-bromo Pd-pi-allyl complex (triphenylphosphine ligand), which alkylates with malonate nucleophile at the terminal position. The presence of acetate ion in the reaction mixture results in some malonate attack being redirected to the central carbon. The acetate ion can come from the ionization of 1-acetoxy-2-bromo-2-propene or by the addition of silver acetate to the reaction mixture. The addition of phenoxide ion to the reaction also causes the same regiochemical phenomena, although harder anions such as methoxide exert no such effect.
Can insulating gaseous layers provide a dielectric barrier discharge effect? (2015)

This letter reports observations of the breakdown characteristics of helium/nitrogen parallel jets when AC voltage was applied across them. Below a certain voltage level, the plasma emission was fully confined to the helium stream as in a traditional dielectric barrier discharge, where the role of the dielectric was played by an insulating gas barrier (nitrogen as compared to helium). The discharge had characteristics of self-organized patterns. Some differences to traditional solid dielectrics are discussed.
A novel endoplasmic stress mediator, Kelch domain containing 7B (KLHDC7B), increased Harakiri (HRK) in the SubAB-induced apoptosis signaling pathway (2021)

Locus for Enterocyte Effacement (LEE)-positive Shiga-toxigenic Escherichia coli (STEC) contributes to many global foodborne diseases, with infection characterized by severe gastrointestinal symptoms, including bloody diarrhea. The incidence of LEE-negative STEC-mediated disease is also increasing globally. Subtilase cytotoxin (SubAB) is released by some LEE-negative STEC strains. It cleaves BiP, which is a chaperone protein located in the endoplasmic reticulum (ER), thereby causing apoptosis induced by ER stress. To date, the apoptotic signaling pathway mediated by SubAB has not been identified. In the current study, RNA-seq analysis showed that SubAB significantly induced the expression of Kelch domain containing 7B (KLHDC7B). We explored the role of KLHDC7B in the SubAB-induced apoptotic pathway. SubAB-induced KLHDC7B mRNA expression was increased after 12 h of incubation of toxin with HeLa cells. KLHDC7B expression was downregulated by knockdown of PKR-like endoplasmic reticulum kinase (PERK), CEBP homologous protein (CHOP), activating transcription factor 4 (ATF4), and CEBP β (CEBPB). KLHDC7B knockdown suppressed SubAB-stimulated CHOP expression, poly(ADP-ribose) polymerase (PARP) cleavage, and cytotoxicity. The over-expressed KLHDC7B was localized to the nucleus and cytosolic fractions. Next, we used RNA-seq to analyze the effect of KLHDC7B knockdown on apoptosis induced by SubAB, and found that the gene encoding for the pro-apoptotic Bcl-2 family protein, Harakiri (HRK), was upregulated in SubAB-treated control cells. However, this effect was not observed in SubAB-treated KLHDC7B-knockdown cells. Therefore, we identified the pathway through which SubAB-induced KLHDC7B regulates HRK expression, which is essential for apoptosis in toxin-mediated ER stress.
Model-based Object Localization and Pose Estimation Method Robust Against the Stereo Miscorrespondence (2011)

The miscorrespondence in stereo image analysis, which is caused by occlusion among images with failure in edge detection, often occurs in real factory environment, and this seriously disturbs the object localization and pose estimation. This work shows that, even under such conditions, the location and attitude of target object can precisely be measured, based on the three base-line trinocular stereo image analysis, using a “model-based verification” method, i.e., a model-based object recognition method including a multi-modal optimization algorithm. This method is suitable for real applications which need object localization and pose estimation, like a bin picking of parts randomly placed on factory automation.
Functionalization of magnetic nanowires by charged biopolymers (2009)

We report on a facile method for the preparation of biocompatible and bioactive magnetic nanowires. The method consists of the direct deposition of polysaccharides by layer-by-layer (LbL) assembly onto a brush of metallic nanowires obtained by electrodeposition of the metal within the nanopores of an alumina template supported on a silicon wafer. Carboxymethylpullulan (CMP) and chitosan (CHI) multilayers were grown on brushes of Ni nanowires; subsequent grafting of an enzyme was performed by conjugating free amine side groups of chitosan with carboxylic groups of the enzyme. The nanowires are finally released by a gentle ultrasonic treatment. Transmission electron microscopy, electron energy-dispersive loss spectroscopy, and x-ray photoelectron spectroscopy indicate the formation of an homogeneous coating onto the nickel nanowires when one, two, or three CMP/CHI bilayers are deposited. This easy and efficient route to the biochemical functionalization of magnetic nanowires could find widespread use for the preparation of a broad range of nanowires with tailored surface properties.
Quasi-Diabatic Band Theory with Localized Crystal Orbital Transformation (1996)

Quasi-diabatic band theory has been developed by using the localized crystal orbital (LCO) transformation to study the electronic structure representing the diabatic behavior of electrons. The theory has been applied to nondoped alternating trans-polyacetylene (t-PA) to understand better the electronic structure from this new standpoint. The results show that the π- (π*-) band of the newly constructed crystal orbital becomes higher (lower) than that of the canonical crystal orbital. The occupation number analysis also indicates that the π-bands near the Fermi energy level play a significant role in the electron transport. These results have been discussed in terms of the LCOs representing the biradical and zwitterionic states.
Muscle-derived cell injection to treat anal incontinence due to obstetric trauma: pilot study with 1 year follow-up (2009)

Injection of autologous myoblasts is safe, well tolerated, and significantly improves symptoms of anal incontinence due to obstetric anal sphincter trauma.
Endothelial Function in HIV-Infected Persons (2006)

HIV-infected patients have significant impairment of endothelial function, and this impairment is worse among those with elevated levels of HIV replication, particularly injection drug users.
Ultrasound- and microbubble-mediated targeted delivery of therapeutic microRNA-loaded nanocarriers to deep liver and kidney tissues in pigs (2019)

Abstract In this study, we designed and validated a platform for ultrasound (US) and microbubble (MB)-mediated delivery of FDA-approved pegylated poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with anticancer microRNAs (miRNAs) to deep tissues in a pig model. Small RNAs have the ability to reprogram tumor cells and sensitize them to clinically used chemotherapy. However, to overcome their short intravascular circulation half-life and achieve controlled and sustained release into tumor cells, anticancer miRNAs need to be encapsulated into NPs. Moreover, focused US combined with gas-filled MBs provides a safe and noninvasive way to improve the permeability of tumor vasculature and increase the delivery efficiency of drug-loaded nanocarriers. A single handheld, curvilinear US array was used in this study for image-guidance and therapy with clinical-grade SonoVue MBs. First, we validated the platform on phantoms to optimize the MB cavitation dose based on acoustic parameters, including peak negative pressure, pulse length, and pulse repetition frequency. We then tested the system in vivo by delivering PLGA-NPs co-loaded with antisense-miRNA-21 and antisense-miRNA-10b in pig liver and kidney. Enhanced miRNA delivery was observed (1.9- to 3.7-fold increase) as a result of the US-MB treatment compared to untreated control regions. Additionally, we used highly fluorescent semiconducting polymer nanoparticles (SPNs) co-delivered with miRNA-loaded PLGA-NPs to visually assess NP delivery. Fluorescent microscopy of SPNs confirmed NP extravasation and showed the presence of particles in the extravascular compartment. Hematoxylin and eosin staining of treated tissues did not reveal tissue damage. The results presented in this manuscript suggest that enhanced delivery of miRNA-loaded NPs to target regions in deep organs is feasible in large animal models using the proposed platform.
Similarities, Differences, and Unknowns in Biology and Management of Three Parasitic Lampreys of North America (2010)

Abstract Sea lampreys, Petromyzon marinus, are invasive to the Laurentian Great Lakes where they have decimated native fishes. Great Lakes sea lampreys have been subjected to control measures for several decades, and the drive to control them has led to major advances in understanding their biology and in informing management. In contrast, anadromous sea and Pacific (Entosphenus tridentatus) lampreys have co-evolved with their oceanic prey. Both of these anadromous lampreys are in decline, and a limited amount of information on their biology has stymied conservation. The tendency has been to make biological inferences about anadromous lampreys based on the Great Lakes sea lamprey without justifiable evidence. We identify areas in which key information is missing for the juvenile (parasitic feeding) phase and adult freshwater spawning migrations, and compare and contrast information for these lampreys. Our comparisons reveal major differences, some intriguing similarities, and key unknowns that will require empirical testing. Resumen la lamprea marina, Petromyzon marinus, es una especie invasiva de la región de los grandes lagos de los Estados Unidos de Norteamérica, en los cuales han diezmado las poblaciones de peces nativos. La lamprea marina de los grandes lagos ha sido sujeto de medidas de control por varias décadas y esta necesidad ha dado lugar a importantes avances en el entendimiento de su biología y manejo. En contraste, la lamprea anádroma y la del Pacífico (Entosphenus tridentatus) han co-evolucionado con sus presas oceánicas. Actualmente las poblaciones de ambas lampreas se encuentran en declive y la escasez de información sobre su biología ha interferido con su conservación. La tendencia ha sido hacer, sin evidencia que lo justifique, inferencias acerca de la lamprea del Pacífico sobre la base de lo que se conoce de la lamprea de los grandes lagos. Se identificaron áreas en las que se carece de información crítica de la fase juvenil (alimentación parasitaria) y de las migraciones reproductivas de los adultos y se comparó y contrastó información para estas lampreas. La comparación reveló diferencias significativas, algunas similitudes interesantes e interrogantes clave que demandarán de comprobación empírica.
Globalisation and Nature Policy: An Integrated Environmental-Economic Framework (1999)

The search for a framework to study globalisation, economics and ecology for nature conservation andbiodiversity protection requires the integration of concepts, theories and models from economics andecology. This allows for the study of interactions between economic and ecological processes, includingprotection of species and biodiversity, sustainable and optimal use of renewable resources, land use andphysical planning, maintenance of nature areas, acquisition of nature areas, and development of outdoorrecreation areas. Economic theories relating to nature and ecosystems have focused on notions of capitaltheory and intertemporal trade-offs, decision making under uncertainty and irreversibility, and marginalvaluation and cost-benefit analysis. Recently, the conservation and valuation of biodiversity, and theresilience of ecological and combined ecological-economic systems, have attracted a great deal of attentionin the environmental and resource economics literature. In addition, the distinction between local and globalcosts and benefits of environmental and biodiversity policies is regarded to have significant impacts oninternational co-operation.Ecology can be incorporated in economic analyses in various ways, notably by offering informationabout the hierarchy of dynamic ecological processes, including population dynamics, ecosystem successionand cycles, and long run trends of selection and evolution. Biodiversity has been linked to resilience in theanalysis of complex ecological-economic systems. Understanding of ecosystem irreversibility anduncertainty can improve economic analysis of decisions with impacts on ecosystem. Ecosystemperformance indicators, such as those proposed around the concept of ecosystem health, can be useful formultidisciplinary modelling and evaluation studies. Finally, monetary valuation studies of goods and servicesprovided by ecosystems can be complemented by detailed information about ecosystem scenarios andfunctions.The paper discusses existing approaches to integrate economics and ecology, reviews the mostimportant studies found in the literature, and suggests a number of general frameworks and models toaddress pressing policy questions relating to globalisation, conservation of biodiversity, sustainable use ofnatural resources, and sustainable land use.
Comparison of the structural characteristics of chromosome VI inSaccharomyces sensu stricto: The divergence, species-dependent features and uniqueness of saké yeasts (1998)

Previous studies have revealed that chromosome VI of saké yeasts is much larger than that of the other strains of Saccharomyces cerevisiae. Southern analysis using segments of chromosome VI of a laboratory strain as probes suggested that the nucleotide sequence of a major portion of this chromosome is conserved, but considerable diversity was found in the distal parts in the other strains. Physical maps also indicated that differences in length of chromosome VI were mainly due to differences in its ends. NotI was found to generate 9 kb and/or 16 kb fragments from the left telomere of chromosome VI in most saké yeasts, but no fragment in the case of AB972. SfiI produced one or two 30-50 kb fragments from the right end of this chromosome in all saké yeasts tested, but produced a 20 kb fragment in the case of AB972. All S. cerevisiae strains not employed in saké brewing were the same as AB972 in these respects. S. paradoxus had one NotI site in chromosome VI, while S. bayanus had two, one of which is possibly common to both species. The SfiI site mentioned above was present in chromosome VI of all species, while that of S. bayanus and S. paradoxus each had a second site distinct from the other. Chromosome VI of S. pastorianus was not distinguishable from that of S. bayanus.