gebhart/patrepeval huggingface dataset:
Identification of new susceptibility loci for IgA nephropathy in Han Chinese (2015)

IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P=7.27 × 10(-10)), ACCS on 11p11.2 (rs2074038, OR=1.14, P=3.93 × 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1.13, P=1.41 × 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P=2.26 × 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P=1.15 × 10(-19); rs12716641, P=9.53 × 10(-9); rs9314614, P=4.25 × 10(-9), multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1, ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.
334 CONSTRUCTION OF A GENETICALLY ENGINEERED PIG EXPRESSING GREEN FLUORESCENT PROTEIN (GFP)-LABELLED PROTEASOMES (2010)

Proteasomes are large protein complexes involved in protein degradation in eukaryotes and undergo dynamic redistribution between cellular compartments. Characterising the cellular localization of proteasomes at various stages of development and in response to stimuli is of interest. We hypothesised that porcine proteasomes could be visualised in vivo via a ubiquitously expressed transgene fusion comprising a proteasomal subunit and green florescent protein (GFP). The full-length sequence for porcine PSMA-1 was first constructed in silico from public data and was used to retrieve a GenBank expressed sequence tag (EST) sequence that appeared to be full length (accession CO946059; kind gift from R. S. Prather). Primers were designed to remove the stop codon and create homology for cloning with InFusion (Clontech, Palo Alto, CA, USA). The amplimer was inserted into pCAG-CreGFP (Addgene plasmid 13776) in place of the Cre coding region. The resulting plasmid (pKW14) was screened via restriction digest and sequenced for confirmation. This plasmid was confirmed functional in porcine fetal fibroblasts. After removal of the plasmid backbones, pKW14, a G418 resistance cassette (NEO), and the chicken egg white matrix attachment region were co-electroporated into male fetal fibroblasts (10 µg of total DNA, 5:2:2 ratio, respectively). Cells were grown in DMEM with 10% fetal bovine serum (FBS) and selection was initiated 36 h after transfection. Following 12 days of selection at 400 mg L–1 G418, colonies were screened by epifluorescence. Positive colonies were harvested and confirmed transgenic for all 3 input DNAs. Positive colonies were randomly pooled as sets of 3 independent integration events. Embryos were reconstructed via SCNT and transferred to 2 recipients. The fusion rates were 70 and 78%, respectively, with transfer numbers of 120 and 125 fused couplets being transferred into synchronized recipients on Day 0 of heat. Both recipients became pregnant and delivered 2 piglets each on Day 114 by Caesarean section. One live piglet was produced from each litter. Of the 2 live-born piglets, 1 survived beyond Day 3 and continues to be healthy. Transgenic status was verified by PCR. Expression was confirmed by epifluorescence of GFP-labelled proteasomes. This founder will be used to establish a model to evaluated cellular localization of proteasomes in vivo and in culture.
Cross-Reactivity to Kynureninase Tolerizes B Cells That Express the HIV-1 Broadly Neutralizing Antibody 2F5 (2019)

2F5 is an HIV-1 broadly neutralizing Ab that also binds the autoantigens kynureninase (KYNU) and anionic lipids. Generation of 2F5-like Abs is proscribed by immune tolerance, but it is unclear which autospecificity is responsible. We sampled the BCR repertoire of 2F5 knock-in mice before and after the first and second tolerance checkpoints. Nearly all small pre-B (precheckpoint) and 35-70% of anergic peripheral B cells (postcheckpoint) expressed the 2F5 BCR and maintained KYNU, lipid, and HIV-1 gp41 reactivity. In contrast, all postcheckpoint mature follicular (MF) B cells had undergone L chain editing that purged KYNU and gp41 binding but left lipid reactivity largely intact. We conclude that specificity for KYNU is the primary driver of tolerization of 2F5-expressing B cells. The MF and anergic B cell populations favored distinct collections of editor L chains; surprisingly, however, MF and anergic B cells also frequently expressed identical BCRs. These results imply that BCR autoreactivity is the primary determinant of whether a developing B cell enters the MF or anergic compartments, with a secondary role for stochastic factors that slightly mix the two pools. Our study provides mechanistic insights into how immunological tolerance impairs humoral responses to HIV-1 and supports activation of anergic B cells as a potential method for HIV-1 vaccination.
Aromatic architecture. Use of the N-methylamide structure as a molecular splint (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAromatic architecture. Use of the N-methylamide structure as a molecular splintKentaro Yamaguchi, Go Matsumura, Hiroyuki Kagechika, Isao Azumaya, Yuji Ito, Akiko Itai, and Koichi ShudoCite this: J. Am. Chem. Soc. 1991, 113, 14, 5474–5475Publication Date (Print):July 1, 1991Publication History Published online1 May 2002Published inissue 1 July 1991https://pubs.acs.org/doi/10.1021/ja00014a060https://doi.org/10.1021/ja00014a060research-articleACS PublicationsRequest reuse permissionsArticle Views657Altmetric-Citations146LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Implementation of an extended simulator for the HF channel on a multi-DSP board (1997)

An extended model for the HF channel is being implemented on a multi-DSP board. As a channel model, an extension of the Watterson (1970) model is proposed, adjusted to encompass both frequency dependencies to serve as a basis for testing wideband modems, and structural variations of the propagation parameters to subject modems using adaptive algorithms and equalisers to proper test conditions. The implementation of the model on a multi-DSP board is accomplished using `Grape' (Graphical Rapid Prototyping Environment). The hardware implementation has to cope both with the complex channel model and the wide bandwidths of the signals that have to be treated. The use of general purpose DSP boards enables a modular and flexible design, which is kept as close to the physical phenomena as possible. There is an option for a division in subbands in order to simplify the processing of wideband signals.
Sr+excitation and electron temperatures in an Sr+laser (1992)

Measurement of the relative intensities of three spectral lines originating from different upper levels in the Sr+ ion has enabled the authors to follow the variation with time of the excitation temperature in the afterglow of a pulsed strontium-vapour laser discharge. From an equation connecting the population of three levels in the presence of a steady-state electron recombination flux, it has been attempted to deduce the corresponding values of the electron temperature throughout the afterglow period in which laser action occurs.
Induction of labor using high-dose or low-dose prostaglandin vaginal pessaries. (1984)

Two hundred women were studied in a randomized controlled trial of induction of labor using high-dose (3 mg) or low-dose (0.5 mg) prostaglandin E2 vaginal pessaries. Induction using 3-mg pessaries was more successful, with a shorter overall induction-delivery interval and less requirement for analgesia, although uterine hyperstimulation occurred in two patients. In contrast, the low-dose regimen did not cause hypertonus and, though less successful in inducing labor, the total dose of prostaglandin E2 used was considerably less than in the 3-mg group. The cesarean section rate when the cervix was initially unfavorable was high in both groups (high dose 18.2%, low dose 16.7%). The response to prostaglandin E2 did not relate closely to the initial cervical state.
Activation regimens to prepare bovine oocytes for intracytoplasmic sperm injection (1998)

Activation of bovine oocytes to produce a single haploid pronucleus in preparation for intracytoplasmic sperm injection (ICSI) has been investigated with various combinations of ionomycin and 6-dimethylaminopurine (DMAP). Effects were evaluated by immunocytochemical staining, chromosomal analysis and assessment of development in vitro. Oocytes matured in vitro were exposed to: ionomycin alone (single or repeated treatments, Groups 1 and 2 respectively), ionomycin followed by DMAP (immediately or after a 3-h delay, Groups 3 and 4), or no treatment (control, Group 5). They were then co-cultured in M199 with bovine oviductal epithelial cells. Activation rates were not significantly different among groups but significantly fewer oocytes in Group 3 extruded a second polar body than in Groups 1, 2, and 4. Most parthenotes (60% to 80%) in Groups 1, 2, and 4 were haploid, whereas 82% in Group 3 were mixoploid or polyploid. Most of the parthenotes (88%) in Group 4 formed a single pronucleus besides extruding the second polar body and were therefore more suitable for ICSI than those of Groups 1 and 2 in which condensed chromosomes predominated. The respective rates of oocyte cleavage in Groups 1 to 4 were 24%, 36%, 70%, and 75%; corresponding blastocyst rates were 1%, 5%, 17%, and 8%. There were significantly fewer cells in the parthenotes of Groups 1, 2, and 4 than of Group 3, or of embryos produced by in vitro fertilization. Thus, delaying the addition of DMAP after ionomycin decreases chromosomal abnormalities and produces a high proportion of activated oocytes suitable for ICSI.
Regional and Temporal Variation of Ventricular and Conduction Tissue Activity During Ventricular Fibrillation in Canines (2021)

[Figure: see text].
Analysis of the 5'-upstream region of mouse P/Q-type Ca2+ channel alpha1A subunit gene for expression in pancreatic islet beta cells using transgenic mice and HIT-T15 cells (2000)

The omega-agatoxin-IVA-sensitive P/Q-type Ca(2+) channel plays a role in insulin release from the pancreatic islets of beta cells. To dissect the molecular mechanisms underlying beta cell expression of the P/Q-type channel, we characterized the 5'-upstream region of the mouse alpha(1A) subunit gene using transgenic mice and HIT insulinoma cells. The E. coli lacZ reporter gene was expressed in pancreatic acini and islets in transgenic mice carrying the 6.3 kb or 3.0 kb of the 5'-upstream region, although those with 1.5 kb or 0. 5 kb of the 5'-upstream region failed to show reporter expression on histological examination. As the expression of alpha(1A)subunit gene could not be detected in acini using RT-PCR analysis, the reporter expression in acini might have been ectopic expression. When linked to the placental alkaline phosphatase reporter gene to examine promoter activity for beta cell expression, the 6.3 kb and 3.0 kb fragment of the 5'-upstream region, but not the smaller 1.5 kb fragment, were able to drive reporter gene expression in HIT cells. The sequence between 3.0 and 1.5 kb upstream of the start codon enhanced thymidine kinase promoter activity in HIT cells, but not in fibroblast NIH3T3 cells. These results suggested that the beta cell-specific elements of the alpha(1A) subunit gene are likely to be located in the distal upstream region (-3021 to-1563) of the 5'-upstream sequence and that the 6.3 kb fragment of the 5'-upstream region alone might be a lack of a negative cis-regulatory element(s) to suppress the alpha(1A) subunit gene expression in acini.
Small Molecule SARM1 Inhibitors Recapitulate the SARM1−/− Phenotype and Allow Recovery of a Metastable Pool of Axons Fated to Degenerate (2021)

Axonal degeneration is responsible for disease progression and accumulation of disability in many neurodegenerative conditions. The axonal degenerative process can generate a metastable pool of damaged axons that remain structurally and functionally viable but fated to degenerate in the absence of external intervention. SARM1, an NADase that depletes axonal energy stores upon activation, is the central driver of an evolutionarily conserved program of axonal degeneration. We identify a potent and selective small molecule isoquinoline inhibitor of SARM1 NADase that recapitulates the SARM1<sup>-/-</sup> phenotype and protects axons from degeneration induced by axotomy or mitochondrial dysfunction. SARM1 inhibition post-mitochondrial injury with rotenone allows recovery and rescues axons that already entered the metastable state. We conclude that SARM1 inhibition with small molecules has the potential to treat axonopathies of the central and peripheral nervous systems by preventing axonal degeneration and by allowing functional recovery of a metastable pool of damaged, but viable, axons.
Thin and robust organic solvent cation exchange membranes for ion separation (2019)

An ultrathin and robust organic solvent cation exchange membrane (CEM) was successfully fabricated for the first time using dissolved Kevlar aramid nanofibers as the casting solution and 4-aminobenzenesulfonic acid (ABS) as the negatively charged functional group <italic>via</italic> an amide condensation reaction for ion separation.
Living carbocationic polymerisation. XI. Copolymerisation of isobutylene with isoprene. Initial investigations (1987)

Abstract The copolymerisation of various isobutylene (IB)‐isoprene (IP) charges has been investigated by the use of the cumyl acetate‐BCl 3 complex initiating system in CH 3 Cl or CH 2 Cl 2 diluents at — 30°C. Conditions have been defined under which charges containing 2 0 120mol % IP lead to living copolymerizations and yield soluble (gel‐free) copolymers containing from 1 2 to 7 8 mol % 1,4‐IP units in the M̄; n = 2400−12 100 range with M̄; w /M̄; n ∼ 1 8. Conversion (rate) and M̄; n decrease with increasing IP in the charge. The reactivity ratios in this IP range are r IB = 2 4 ± 0 35 and r IP = 4 5 ± 3 0, i.e. r IB r IP = 10 8; nonetheless the copolymers are statistical because of the very low IP contents in the charge. With 20–50 mol % IP in the charge two or more contiguous IP units will be formed at the growing chain end which may lead to cyclisation. Cyclisation leads to proton elimination which ultimately results in chain transfer to monomer. A mechanism has been developed that accounts for the observations and points the way for further research.
Equalization of nonuniform EDFA gain using a fiber loop mirror (2002)

We experimentally demonstrate gain equalization and show that after 1,500-km transmission, the maximum power differential is reduced from 30 dB to 2 dB for three WDM channels covering a 9-nm wavelength range. By varying the polarization inside the fiber loop mirror, the filter peak wavelength can be tuned by greater than 7 nm, and the filter shape and filter bandwidth can also be modified.
Experimental Comparison of Cap and Cup Probabilistically Shaped PAM for O-Band IM/DD Transmission System (2021)

For 200Gbit/s net rates, uniform PAM-4, 6 and 8 are experimentally compared against probabilistic shaped PAM-8 cap and cup variants. In back-to-back and 20km measurements, cap shaped 80GBd PAM-8 outperforms 72GBd PAM-8 and 83GBd PAM-6 by up to 5.17dB and 2.17dB in receiver sensitivity, respectively.
Comparative analysis of human Wharton’s jelly mesenchymal stem cells derived from different parts of the same umbilical cord (2017)

Easy isolation, lack of ethical issues, high proliferation, multi-lineage differentiation potential and immunomodulatory properties of umbilical cord (UC)-derived mesenchymal stem cells (MSCs) make them a valuable tool in stem cell research. Recently, Wharton's jelly (WJ) was proven as the best MSC source among various compartments of UC. However, it is still unclear whether or not Wharton's jelly-derived MSCs (WJMSCs) from different parts of the whole cord exhibit the same characteristics. There may be varied MSCs present in different parts of WJ throughout the length of the UC. For this purpose, using an explant attachment method, WJMSCs were isolated from three different parts of the UC, mainly present towards the placenta (mother part), the center of the whole cord (central part) and the part attached to the fetus (baby part). WJMSCs from all three parts were maintained in normal growth conditions (10% ADMEM) and analyzed for mesenchymal markers, pluripotent genes, proliferation rate and tri-lineage differentiation potential. All WJMSCs were highly proliferative, positively expressed CD90, CD105, CD73 and vimentin, while not expressing CD34, CD45, CD14, CD19 or HLA-DR, differentiated into adipocytes, osteocytes and chondrocytes and expressed pluripotency markers OCT-4, SOX-2 and NANOG at gene and protein levels. Furthermore, MSCs derived from all the parts were shown to have potency towards hepatocyte-like cell differentiation. Human bone marrow-derived MSCs were used as a positive control. Finally, we conclude that WJMSCs derived from all the parts are valuable sources and can be efficiently used in various fields of regenerative medicine.
Silicon photonics: some remaining challenges (2016)

This paper discusses some of the remaining challenges for silicon photonics, and how we at Southampton University have approached some of them. Despite phenomenal advances in the field of Silicon Photonics, there are a number of areas that still require development. For short to medium reach applications, there is a need to improve the power consumption of photonic circuits such that inter-chip, and perhaps intra-chip applications are viable. This means that yet smaller devices are required as well as thermally stable devices, and multiple wavelength channels. In turn this demands smaller, more efficient modulators, athermal circuits, and improved wavelength division multiplexers. The debate continues as to whether on-chip lasers are necessary for all applications, but an efficient low cost laser would benefit many applications. Multi-layer photonics offers the possibility of increasing the complexity and effectiveness of a given area of chip real estate, but it is a demanding challenge. Low cost packaging (in particular, passive alignment of fibre to waveguide), and effective wafer scale testing strategies, are also essential for mass market applications. Whilst solutions to these challenges would enhance most applications, a derivative technology is emerging, that of Mid Infra-Red (MIR) silicon photonics. This field will build on existing developments, but will require key enhancements to facilitate functionality at longer wavelengths. In common with mainstream silicon photonics, significant developments have been made, but there is still much left to do. Here we summarise some of our recent work towards wafer scale testing, passive alignment, multiplexing, and MIR silicon photonics technology.
Investigation of the composite structure of peak 5 in the thermoluminescent glow curve of LiF:Mg,Ti (TLD-100) using optical bleaching (1999)

The composite structure of glow peak 5 in LiF:Mg,Ti (TLD-100), has been investigated using optical bleaching by 310 nm (4 eV) light. The decay of composite peak 5 and the growth of peak 4 are described by two exponential components of the same mean lives for both peaks. Using computerized glow curve deconvolution and contrary to previous investigations, it is determined that peak 4 does not decrease in intensity at long bleaching times and is therefore not associated with the 4 eV absorption band. The fast and slow components of the exponential decay are associated with the bleaching of peaks 5a and 5, respectively. Optical bleaching as a function of the temperature of post-irradiation annealing reveals that the conversion efficiency of peak 5a to peak 4 is very high, at a constant value of approximately 30%, whereas the conversion efficiency of peak 5 is no greater than a few per cent. The behaviour of the conversion efficiency as a function of the temperature of the post-irradiation anneal is explained in the framework of the spatially correlated trapping centre/luminescent (TC/LC) centre model. In this model, the TL of peak 5a results from the geminate recombination of a locally trapped electron-hole pair: peak 5 results from recombination via electron diffusion in the conduction band following thermal release of a singly-trapped electron in the TC/LC structure. Peak 4 arises from a singly-trapped hole in the TC/LC structure. The high conversion efficiency of peak 5a to peak 4 arises from direct optical ionization of the electron in the electron-hole pair, leaving behind a singly-trapped hole (glow peak 4), a direct mechanism not subject to competitive processes. Optical ionization of the `singly-trapped' electron (peak 5), however, can lead to peak 4 only via a multi-stage mechanism involving charge carrier transport in the conduction band, a mechanism subject to competitive processes, which leads to an order-of-magnitude decrease in the observed efficiency
The Role of Mcl-1 inS. aureus-Induced Cytoprotection of Infected Macrophages (2013)

As a facultative intracellular pathogen, Staphylococcus aureus invades macrophages and then promotes the cytoprotection of infected cells thus stabilizing safe niche for silent persistence. This process occurs through the upregulation of crucial antiapoptotic genes, in particular, myeloid cell leukemia-1 (MCL-1). Here, we investigated the underlying mechanism and signal transduction pathways leading to increased MCL-1 expression in infected macrophages. Live S. aureus not only stimulated de novo synthesis of Mcl-1, but also prolonged the stability of this antiapoptotic protein. Consistent with this, we proved a crucial role of Mcl-1 in S. aureus-induced cytoprotection, since silencing of MCL1 by siRNA profoundly reversed the cytoprotection of infected cells leading to apoptosis. Increased MCL1 expression in infected cells was associated with enhanced NFκB activation and subsequent IL-6 secretion, since the inhibition of both NFκB and IL-6 signalling pathways abrogated Mcl-1 induction and cytoprotection. Finally, we confirmed our observation in vivo in murine model of septic arthritis showing the association between the severity of arthritis and Mcl-1 expression. Therefore, we propose that S. aureus is hijacking the Mcl-1-dependent inhibition of apoptosis to prevent the elimination of infected host cells, thus allowing the intracellular persistence of the pathogen, its dissemination by infected macrophages, and the progression of staphylococci diseases.
Cover Image (2019)

The cover image, by Daniel F. Klessig et al., is based on the Original Article Nematode ascaroside enhances resistance in a broad spectrum of plant–pathogen systems. DOI: 10.1111/jph.12795. Photo credit: Cover image © Aardra Kachroo University of Kentucky Images