gebhart/patrepeval huggingface dataset:
Co-expression of Defective Luteinizing Hormone Receptor Fragments Partially Reconstitutes Ligand-induced Signal Generation (1997)

Gonadotropin receptors are unique members of the seven-transmembrane (TM), G protein-coupled receptor family with a large extracellular (EC) sequence forming the high-affinity ligand binding domain. In a patient with Leydig cell hypoplasia, we identified a mutant LH receptor that is truncated at TM5. This protein retains limited ligand binding ability but cannot mediate cAMP responses. To study interactions between receptor fragments defective in either ligand binding or signal transduction, we co-expressed this truncated receptor together with a chimeric receptor containing the EC region of the FSH receptor and the TM region of the LH receptor. Although the chimeric receptor could not respond to human chorionic gonadotropin in producing cAMP, co-expression with the truncated LH receptor allowed partial restoration of ligand signaling through intermolecular interactions. In addition, co-expression of the same truncated LH receptor with an N-terminally truncated LH receptor that lacked the EC ligand binding domain also partially restored ligand signaling. Further shortening of the TM region in the mutant receptor found in the patient indicated that the EC domain and TM1 were sufficient for interactions with the N terminally truncated receptor. In contrast, co-expression of the N terminally truncated receptor together with cell-associated or soluble EC region of the LH receptor did not allow ligand signaling. Unlike thrombin receptors, co-expression of the anchored EC region of the LH receptor together with the N-terminally truncated receptor did not allow ligand signaling despite moderate levels of human chorionic gonadotropin binding in transfected cells. These studies demonstrate that the co-expression of binding (+)/signaling (-) and binding (-)/signaling (+) receptor fragments partially restores ligand-induced signal generation and indicate the importance of TM1 of the LH receptor in the proper orientation of the EC ligand binding domain.
Lateral bipolar transistor fabricated on a deep-submicron technology (2003)

The performance of a NPN Lateral Bipolar Transistor (LBJT), based on a minimally modified submicron MOSFET without gate oxide, was studied by means of simulations and measurements on fabricated devices. Large-tilt angle, single-sided implants were successfully used to control the breakdown voltage by tailoring the asymmetric collector doping profile in a self-aligned way. Because of the lack of carrier confinement in the base of devices built on bulk silicon the common emitter current gain is lower than one. Two options for solving this problem were studied using simulators: Building the LBJT on Silicon-On-Insulator (SOI) or introducing SiGe into the base. This project was developed in close cooperation with National Semiconductor Corp., Santa Clara, California.
Improved Cell Therapy Protocols for Parkinson's Disease Based on Differentiation Efficiency and Safety of hESC-, hiPSC-, and Non-Human Primate iPSC-Derived Dopaminergic Neurons (2013)

The main motor symptoms of Parkinson's disease are due to the loss of dopaminergic (DA) neurons in the ventral midbrain (VM). For the future treatment of Parkinson's disease with cell transplantation it is important to develop efficient differentiation methods for production of human iPSCs and hESCs-derived midbrain-type DA neurons. Here we describe an efficient differentiation and sorting strategy for DA neurons from both human ES/iPS cells and non-human primate iPSCs. The use of non-human primate iPSCs for neuronal differentiation and autologous transplantation is important for preclinical evaluation of safety and efficacy of stem cell-derived DA neurons. The aim of this study was to improve the safety of human- and non-human primate iPSC (PiPSC)-derived DA neurons. According to our results, NCAM(+) /CD29(low) sorting enriched VM DA neurons from pluripotent stem cell-derived neural cell populations. NCAM(+) /CD29(low) DA neurons were positive for FOXA2/TH and EN1/TH and this cell population had increased expression levels of FOXA2, LMX1A, TH, GIRK2, PITX3, EN1, NURR1 mRNA compared to unsorted neural cell populations. PiPSC-derived NCAM(+) /CD29(low) DA neurons were able to restore motor function of 6-hydroxydopamine (6-OHDA) lesioned rats 16 weeks after transplantation. The transplanted sorted cells also integrated in the rodent brain tissue, with robust TH+/hNCAM+ neuritic innervation of the host striatum. One year after autologous transplantation, the primate iPSC-derived neural cells survived in the striatum of one primate without any immunosuppression. These neural cell grafts contained FOXA2/TH-positive neurons in the graft site. This is an important proof of concept for the feasibility and safety of iPSC-derived cell transplantation therapies in the future.
Glucose metabolism in the rat small intestine: the effect of glucose analogues on hexokinase activity (Short Communication) (1973)

The effect of intubation of starved rats with solutions of glucose, 3-O-methylglucose, mannose, 2-deoxyglucose and sorbitol on the subcellular location of hexokinase in the mucosa of the small intestine was studied. Glucose, 3-O-methylglucose and mannose caused the soluble hexokinase activity to rise to a value similar to that found in fed animals, whereas sorbitol and 2-deoxyglucose caused smaller increases.
Stability of Volterra system with impulsive effect (1991)

Sufficient conditions for uniform stability and uniform asymptotic stability of impulsive integrodifferential equations are investigated by constructing a suitable piecewise continuous Lyapunov‐like functionals without the decresent property. A result which establishes no pulse phenomena in the given system is also discussed.
Noncovalent Wild-type–Sparing Inhibitors of EGFR T790M (2012)

EGFR-mutant lung cancer patients who respond to currently used EGFR kinase inhibitors invariably develop drug resistance, which is associated with the EGFR T790M resistance mutation in about half these cases. We unexpectedly identified a class of reversible potent inhibitors of EGFR T790M that do not inhibit wild-type EGFR, revealing a promising therapeutic strategy to overcome T790M-associated drug-resistant lung cancers.
Structural and functional analysis of the PDZ domains of human HtrA1 and HtrA3 (2007)

High-temperature requirement A (HtrA) and its homologs contain a serine protease domain followed by one or two PDZ domains. Bacterial HtrA proteins and the mitochondrial protein HtrA2/Omi maintain cell function by acting as both molecular chaperones and proteases to manage misfolded proteins. The biological roles of the mammalian family members HtrA1 and HtrA3 are less clear. We report a detailed structural and functional analysis of the PDZ domains of human HtrA1 and HtrA3 using peptide libraries and affinity assays to define specificity, structural studies to view the molecular details of ligand recognition, and alanine scanning mutagenesis to investigate the energetic contributions of individual residues to ligand binding. In common with HtrA2/Omi, we show that the PDZ domains of HtrA1 and HtrA3 recognize hydrophobic polypeptides, and while C-terminal sequences are preferred, internal sequences are also recognized. However, the details of the interactions differ, as different domains rely on interactions with different residues within the ligand to achieve high affinity binding. The results suggest that mammalian HtrA PDZ domains interact with a broad range of hydrophobic binding partners. This promiscuous specificity resembles that of bacterial HtrA family members and suggests a similar function for recognizing misfolded polypeptides with exposed hydrophobic sequences. Our results support a common activation mechanism for the HtrA family, whereby hydrophobic peptides bind to the PDZ domain and induce conformational changes that activate the protease. Such a mechanism is well suited to proteases evolved for the recognition and degradation of misfolded proteins.
Prolactin Prevents Chronic Stress-Induced Decrease of Adult Hippocampal Neurogenesis and Promotes Neuronal Fate (2009)

Chronic exposure to stress results in a reduction of hippocampal neurogenesis and of hippocampal volume. We examined whether prolactin (PRL), a regulator of the stress response and stimulator of neurogenesis in the subventricular zone, influences neurogenesis in the hippocampal dentate gyrus (DG) of chronically stressed adult C57BL/6 male mice. Chronically stressed (4 h daily immobilization for 21 d) or nonstressed mice were treated with either ovine PRL or vehicle between days 1-14. BrdU was injected daily between days 1-7 to evaluate cell survival and fate, or twice on day 21 to evaluate cell proliferation. Hippocampal cell proliferation was unchanged by either stress exposure or PRL at the end of the treatments. In contrast, the number of cells in the DG that incorporated BrdU during the first phase of the experiment and survived to the end of the experiment was decreased in vehicle-treated stressed mice compared with PRL- or vehicle-treated nonstressed control mice. Stressed animals receiving PRL had significantly more BrdU-labeled cells than vehicle-treated stressed mice at this time point. Cell fate analysis revealed a higher percentage of neurons in PRL- compared with vehicle-treated stressed mice. The results demonstrate that PRL protects neurogenesis in the DG of chronically stressed mice and promotes neuronal fate.
One-step microfluidic generation of pre-hatching embryo-like core–shell microcapsules for miniaturized 3D culture of pluripotent stem cells (2013)

A novel core–shell microcapsule system is developed in this study to mimic the miniaturized 3D architecture of pre-hatching embryos with an aqueous liquid-like core of embryonic cells and a hydrogel-shell of zona pellucida. This is done by microfabricating a non-planar microfluidic flow-focusing device that enables one-step generation of microcapsules with an alginate hydrogel shell and an aqueous liquid core of cells from two aqueous fluids. Mouse embryonic stem (ES) cells encapsulated in the liquid core are found to survive well (>92%). Moreover, ~20 ES cells in the core can proliferate to form a single ES cell aggregate in each microcapsule within 7 days while at least a few hundred cells are usually needed by the commonly used hanging-drop method to form an embryoid body (EB) in each hanging drop. Quantitative RT-PCR analyses show significantly higher expression of pluripotency marker genes in the 3D aggregated ES cells compared to the cells under 2D culture. The aggregated ES cells can be efficiently differentiated into beating cardiomyocytes using a small molecule (cardiogenol C) without complex combination of multiple growth factors. Taken together, the novel 3D microfluidic and pre-hatching embryo-like microcapsule systems are of importance to facilitate in vitro culture of pluripotent stem cells for their ever-increasing use in modern cell-based medicine.
The TOR Kinases Link Nutrient Sensing to Cell Growth (2001)

Rapamycin is an immunosuppressive natural product that inhibits the proliferation of T-cells in response to nutrients and growth factors. Rapamycin binds to the peptidyl-prolyl isomerase FKBP12 and forms protein-drug complexes that inhibit signal transduction by the TOR kinases. The FKBP12 and TOR proteins are conserved from fungi to humans, and in both organisms the TOR signaling pathway plays a role in nutrient sensing. In response to nitrogen sources or amino acids, TOR regulates both transcription and translation, enabling cells to appropriately respond to growth-promoting signals. Rapamycin is having a profound impact on clinical medicine and was approved as an immunosuppressant for transplant recipients in 1999. Ongoing clinical studies address new clinical applications for rapamycin as an antiproliferative drug for chemotherapy and invasive cardiology.
Failure of attenuated temperature-sensitive influenza A (H3N2) virus to induce heterologous interference in humans to parainfluenza type 1 virus (1975)

The present investigation was undertaken to determine if a candidate live vaccine virus, influenza A/Hong Kong/68-ts-1 [E] (H3N2), induced heterologous interference against an interferon-sensitive, wild-type, parainfluenza type 1 challenge virus. The parainfluenza virus was administered 7 days after Hong Kong/68-ts-1 [E] virus infection. The clinical response, daily quantitative virus shedding, interferon production, and serum and nasal wash antibody responses were determined in an experimental group (influenza A virus followed by parainfluenza virus) and 10 volunteers in a control group (parainfluenza virus only). The volunteers were selected on the basis of susceptibility to the two viruses, i.e. serum hemagglutination-inhibition antibody titer of is less than or greater to 1:8 for influenza virus and low nasal wash antibody titer (is less than or greater to 1:8) for parainfluenza virus. Despite a 100% infection rate in the Hong Kong/68-ts-1 [E] vaccinees, no heterologous interference was induced against the parainfluenza type 1 virus challenge.
A Synthetic CD4-CDR3 Peptide Analog Enhances Skin Allograft Survival Across a MHC Class II Barrier (1998)

The efficacy of a synthetic peptide analogue (rD-mPGPtide), mimicking the CDR3 region in the first domain of the CD4 surface molecule, was investigated in a murine model for CD4+ T cell-mediated skin allograft rejection. A single injection of rD-mPGPtide shortly before transplantation exhibited significantly prolonged graft survival in the B6 anti-B6.C-H2bm12 MHC class II-disparate strain combination. Long-term graft survival (>100 days) was achieved when thymectomized adult recipient mice were transplanted along with rD-mPGPtide treatment. The peptide also affected secondary rechallenge responses with MHC class II allografts. In addition, the inhibitory effect of the rD-mPGPtide in this transplantation model was directed against CD4+ T cells and was exclusively specific toward donor alloantigen. In vitro analysis of CD4+ T cells isolated from the draining lymph nodes of rD-mPGPtide-treated recipients indicated a 450-fold decrease in precursor frequency in response to donor allostimulation compared with the untreated control group. There was also significant down-regulation of the frequency of IL-2-, IFN-gamma-, and IL-4-producing CD4+ T cells upon in vitro allogeneic restimulation of host cells 4 days posttransplantation. However, these same CD4+ T cells maintained the capacity to produce normal cytokine levels upon third-party allostimulation. Thus, these studies demonstrate that a CD4-CDR3 peptide analogue can specifically and effectively prolong skin graft survival across MHC class II barriers.
A Survey of Current Approaches for Mapping of Relational Databases to RDF (2009)

This document surveys current techniques, tools and applications for mapping between Relational Databases (RDB) and the Resource Description Framework (RDF). Basic knowledge of RDF as well as RDB
The kinetics of cytological events during double fertilization in Zea mays L. (1994)

By using a clearing method, the process of double fertilization in Zea mays L. (line A 188) was analysed and the precise sequence of events was determined. The period from pollen tube arrival to gamete fusion was relatively short, possibly less than 1 h. The karyogamy was of premitotic type, and the time from the contact of male and female nuclei to the fusion of male and female nucleoli was about 5 h in the egg cell and 3 h in the central cell. In the central cell, the sperm nucleus fused with either one of the polar nuclei or the secondary nucleus, the latter being observed for the first time in maize. The zygote was in the resting period for 13–16 h before division commenced, changing the cell polarity during karyogamy and the resting period. The primary endosperm nucleus divided immediately after karyogamy was completed in the central cell. The embryo sacs with two‐celled proembryos contained four to eight endosperm nuclei. The timetable of fertilization events could be a standard for further studies on in vitro fertilization at the cytological and molecular levels.
Duplication of medial erosion in unicompartmental knee arthroplasties (1995)

Osteoarthritis of the medial compartment of the knee often shows a specific pattern of anterior wear. Review of our revisions from a series of medial metal-backed Brigham unicondylar knee replacements performed between 1983 and 1989 showed that this wear pattern was common on the tibial polyethylene surface. We reviewed these cases retrospectively to compare the pattern of preoperative erosion with the wear of the prosthesis. In all 14 knees with severe anterior wear in a unicompartmental replacement, the prearthroplasty radiographs showed similar patterns, suggesting that the implanted tibial component may continue to be subjected to the same localised stresses that precipitated the failure of the original articular cartilage. Many tibial components implanted during the 1980s had an unacceptably thin anterior rim of polyethylene and it seems that greater thickness is essential at the anterior and peripheral margins of the tibial plateau.
Pseudo-lignin and pretreatment chemistry (2010)

The formation of pseudo-lignin by the combination of carbohydrate and lignin degradation products has been proposed to be responsible for the increased Klason lignin content in biomass pretreated under acidic conditions. Direct evidence for the presence of pseudo-lignin has never been presented. The formation of additional lignin-like material may be detrimental to enzymatic hydrolysis due to the non-productive binding of enzymes with lignin. To investigate the chemistry of pseudo-lignin formation, dilute acid pretreatments were performed on delignified hybrid poplar biomass under conditions of varying severity. The results show a progressive increase in the Klason lignin content of the acid pretreated material with increasing pretreatment severity. NMR and FT-IR spectroscopic characterization shows the development of aliphatic, unsaturated and carbonyl carbon functionalities in the samples pretreated at higher severities. Given the very low Klason lignin content of the starting material, acid catalyzed dehydration of carbohydrates is responsible for the formation of pseudo-lignin.
Cytokinin-mediated control of leaf longevity by AHK3 through phosphorylation of ARR2 in Arabidopsis (2006)

Cytokinins are plant hormones with profound roles in growth and development, including control of leaf longevity. Although the cytokinin signal is known to be perceived by histidine kinase receptors, the underlying molecular mechanism and specificity of the receptors leading to delayed leaf senescence have not yet been elucidated. Here, we found that AHK3, one of the three cytokinin receptors in Arabidopsis, plays a major role in controlling cytokinin-mediated leaf longevity through a specific phosphorylation of a response regulator, ARR2. This result was obtained through identification of a gain-of-function Arabidopsis mutant that shows delayed leaf senescence because of a missense mutation in the extracellular domain of AHK3. A loss-of-function mutation in AHK3, but not of the other cytokinin receptors, conferred a reduced sensitivity to cytokinin in cytokinin-dependent delay of leaf senescence and abolished cytokinin-dependent phosphorylation of ARR2. Consistently, transgenic overexpression of wild-type, but not an unphosphorylatable mutant ARR2, led to delayed senescence of leaves.
Fatty acid modulation of K+ channels in taste receptor cells: gustatory cues for dietary fat (1997)

In an attempt to determine the chemosensory cues, if any, provided by fats in the oral cavity, we have performed patch-clamp recordings on isolated rat taste receptor cells during application of free fatty acids. Cis-polyunsaturated fatty acids, when applied extracellularly, inhibit delayed-rectifying K+ channels. In a subset of cells, these fatty acids also enhance inwardly rectifying K+ currents. Saturated, monounsaturated, and trans-polyunsaturated fatty acids have no significant effect on K+ currents. These effects do not involve activation of G protein-mediated pathways, including protein kinase C and protein kinase A, lipoxygenase pathways, cyclooxygenase pathways, or cytochrome P-450 pathways, consistent with direct effects on these ion channels or closely associated proteins. The net effect of fatty acids is to prolong stimulus-induced depolarizations of taste receptor cells, and we propose the effects on K+ channels represent the mechanism by which fats are detected by receptor cells in the oral cavity.
The immunomodulator glatiramer acetate augments the expression of neurotrophic factors in brains of experimental autoimmune encephalomyelitis mice (2005)

Neurotrophins (NTs) such as BDNF, NT-3, and NT-4 are important modulators of neuronal function and survival. Their expression in the CNS after various insults is thus of major therapeutic consequence. Glatiramer acetate [(GA) Copaxone], an approved drug for the treatment of multiple sclerosis, has been shown to induce Th2/3 cells that accumulate in the CNS, expressing in situ antiinflammatory cytokines and BDNF. In the present study, we investigated whether s.c. injections of GA, applied at various stages of experimental autoimmune encephalomyelitis, affect the expression of NTs, particularly BDNF, in the brain. In untreated experimental autoimmune encephalomyelitis mice, the expression of NTs was elevated shortly after disease appearance but subsequently declined below that of naive mice. In contrast, GA treatment led to sustained augmentation in the expression of BDNF, NT-3, and NT-4 in various brain regions as demonstrated by histological analysis of immunostained brain sections. GA treatment, even when started 45 days after disease induction, restored the impaired level of NTs to that of healthy mice. BDNF elevation after GA treatment was demonstrated on both protein and mRNA levels. Prominent staining was manifested not only by infiltrating GA-induced T cells, but also by CNS resident cells (neurons and astrocytes), indicative of a bystander therapeutic effect. Of importance, in GA-treated mice, intense BDNF expression was manifested by neuronal progenitors that migrated into lesions in injured regions. These results indicate that the immunomodulator GA exerts not only an antiinflammatory effect, but also enhances neuroprotection and regeneration of neural elements in the diseased brain.
Memory-efficient turbo decoder architectures for LDPC codes (2003)

In this paper, we propose a turbo decoding message-passing (TDMP) algorithm to decode regular and irregular low-density parity-check (LDPC) codes. The TDMP algorithm has two main advantages over the commonly employed two-phase message-passing algorithm. First, it exhibits a faster convergence behavior (up to 50% less iterations), and improvement in coding gain (up to an order of magnitude for moderate-to-high SNR and small number of iterations). Second, the corresponding decoder architecture has a significantly reduced memory requirement that amounts to a savings of (75 + 25n//spl Sigma/ node-degrees)% > 75% for code-length n. A decoder architecture featuring the TDNW algorithm is also presented. Furthermore, we propose a new structure on the parity-check matrix of an LDPC code based on permutation matrices aimed at reducing interconnect complexity and improving decoding throughput. In addition, we construct a wide range of LDPC codes based on Ramanujan graphs which possess this structure.