gebhart/patrepeval huggingface dataset:
Genotyping of the N-acetyltransferase2 Polymorphism in the Prediction of Adverse Drug Reactions to Isoniazid in Japanese Patients (2002)

To investigate the association between NAT2 genotypes and the incidence of isoniazid (INH)-induced adverse reactions, in the hope of identifying a pharmacogenetic approach that could be useful in the prediction and prevention of adverse reactions in Japanese patients, we retrospectively studied the genotypes of NAT2 in 102 Japanese patients treated with INH (without rifampicin co-administration). The subjects were classified into three groups according to their genotypes: rapid-type, intermediate-type, and slow-type. The clinical conditions of the patients were followed-up in order to evaluate the development of any adverse drug reactions (ADRs) and correlate them with patient genotypes. Six out of the 102 patients (5.9%) developed various ADRs following INH treatment. These reactions included nausea/vomiting, fever, visual impairment, and peripheral neuritis. We found a statistically significant difference between the incidence of ADRs and NAT2 genotype. The incidence of ADRs was significantly higher in the slow type than in the other two types, as 5 out of the 6 ADR patients were of the slow-type, and the other one was of the intermediate-type, while no patients of the rapid-type developed any ADRs. The results indicated that the genes coding for slow acetylation were associated with the incidence of serious ADRs following INH treatment. Our findings suggest that determination of NAT2 genotype might be clinically useful in the evaluation of patients at high risk of developing ADRs induced by INH.
Nanoporous Thin Films Formed by Salt-Induced Structural Changes in Multilayers of Poly(acrylic acid) and Poly(allylamine) (2001)

We report here on the influence of changes in the solution salt concentration on the structure of multilayers of weak polyelectrolytes. For poly(acrylic acid) (PAA) and poly(allylamine) (PAH) multilayers assembled by the layer-by-layer process in the presence of sodium chloride, washing with pure water after deposition of each layer produces films with considerable surface roughness (root-mean-squared (rms) roughness ∼17 nm for a 10 layer film), as assessed by scanning force microscopy. In contrast, relatively smooth (rms roughness ∼1 nm) and homogeneous PAH/PAA multilayer films are formed when the salt concentration is kept constant both during the assembly process and in the washing steps. For such smooth films, subsequent exposure to pure water leads to the introduction of regular, discrete, nanometer-sized pores, thus providing a means of introducing lateral structure into the PAH/PAA multilayer films. Electrochemical measurements revealed that the pores formed in less than 10 min. The sensitivity of the multilayer films to salt as well as the subsequent creation of nanopores potentially makes them attractive candidates for use in controlled-release applications where defined permeability characteristics are desired.
Analysis of CHO Cells Metabolic Redistribution in a Glutamate-Based Defined Medium in Continuous Culture (2001)

The effect of glutamine replacement by glutamate and the balance between glutamate and glucose metabolism on the redistribution of t-PA-producing recombinant CHO cells metabolism is studied in a series of glucose shift down and shift up experiments in continuous culture. These experiments reveal the existence of multiple steady states, and experimental data are used to perform metabolic flux analysis to gain a better insight into cellular metabolism and its redistribution. Regulation of glucose feed rate promotes a higher efficiency of glucose and nitrogen source utilization, with lower production of metabolic byproducts, but this reduces t-PA specific production rate. This reduction under glucose limitation can be attributed to the fact that the cells are forced to efficiently utilize the carbon and energy source for growth, impairing the production of dispensable metabolites. It is, therefore, the combination of growth rate and carbon and energy source availability that determines the level of t-PA production in continuous culture.
The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo (1998)

Mutations in the SMAD4/DPC4 tumor suppressor gene, a key signal transducer in most TGFbeta-related pathways, are involved in 50% of pancreatic cancers. Homozygous Smad4 mutant mice die before day 7.5 of embryogenesis. Mutant embryos have reduced size, fail to gastrulate or express a mesodermal marker, and show abnormal visceral endoderm development. Growth retardation of the Smad4-deficient embryos results from reduced cell proliferation rather than increased apoptosis. Aggregation of mutant Smad4 ES cells with wild-type tetraploid morulae rescues the gastrulation defect. These results indicate that Smad4 is initially required for the differentiation of the visceral endoderm and that the gastrulation defect in the epiblast is secondary and non-cell autonomous. Rescued embryos show severe anterior truncations, indicating a second important role for Smad4 in anterior patterning during embryogenesis.
Appointment breaking: causes and solutions. (1992)

From a review of research on health care appointment breaking, the authors find that patient demographic characteristics, psychosocial problems, previous appointment keeping, health beliefs, and situational factors predict no-show behavior. Suggestions are offered for designing the marketing mix to increase patient appointment keeping. Methods for mitigating the negative effects of no-shows on health care providers are described.
Detection of circulating dna by counterimmunoelectrophoresis (cie) (1973)

Abstract Using counterimmunoelectrophoresis, DNA may be detected at concentrations as low as 1.5 μ/ml in plasma and 0.2 μg/ml in serum . Serum, however, was not suitable for this study because DNA was sporadically released into serum during the clotting process. Counterimmunoelectrophoresis is at least ten times more sensitive than simple immunodiffusion in the detection of DNA. DNA was found in plasma in a variety of illnesses which are delineated in this study.
Tuning CRISPR-Cas9 Gene Drives in Saccharomyces cerevisiae (2018)

Control of biological populations is an ongoing challenge in many fields, including agriculture, biodiversity, ecological preservation, pest control, and the spread of disease. In some cases, such as insects that harbor human pathogens (<i>e.g.</i>, malaria), elimination or reduction of a small number of species would have a dramatic impact across the globe. Given the recent discovery and development of the CRISPR-Cas9 gene editing technology, a unique arrangement of this system, a nuclease-based "gene drive," allows for the super-Mendelian spread and forced propagation of a genetic element through a population. Recent studies have demonstrated the ability of a gene drive to rapidly spread within and nearly eliminate insect populations in a laboratory setting. While there are still ongoing technical challenges to design of a more optimal gene drive to be used in wild populations, there are still serious ecological and ethical concerns surrounding the nature of this powerful biological agent. Here, we use budding yeast as a safe and fully contained model system to explore mechanisms that might allow for programmed regulation of gene drive activity. We describe four conserved features of all CRISPR-based drives and demonstrate the ability of each drive component-Cas9 protein level, sgRNA identity, Cas9 nucleocytoplasmic shuttling, and novel Cas9-Cas9 tandem fusions-to modulate drive activity within a population.
Differential Responsiveness of a Splice Variant of the Human Type I Interferon Receptor to Interferons (1996)

Chinese hamster ovary cells containing the yeast artificial chromosome F136C5 (alphaYAC) respond to all type I human interferons including IFN-alphaA, IFN-beta, and IFN-omega. The alphaYAC contains at least two genes encoding interferon-alpha receptor (IFN-alphaR) chains that are required for response to type I human interferons: Hu-IFN-alphaR1 and Hu-IFN-alphaR2. We previously isolated a splice variant of the Hu-IFN-alphaR1 chain designated Hu-IFN-alphaR1s. Chinese hamster ovary cells containing a disrupted alphaYAC, which contains a deletion in the human IFNAR1 gene, were transfected with expression vectors for the Hu-IFN-alphaR1 and Hu-IFN-alphaR1s chains. With these cells, two type I interferons have been identified which can interact with the splice variant (Hu-IFN-alphaR1s) and with the Hu-IFN-alphaR1 chains: Hu-IFN-alphaA and IFN-omega. Two other type I interferons, Hu-IFN-alphaB2 and Hu-IFN-alphaF, are capable of signaling through the Hu-IFN-alphaR1 chain only and cannot utilize the splice variant Hu-IFN-alphaR1s. Hu-IFN-alphaR1 and Hu-IFN-alphaR1s differ in that the latter is missing a single subdomain of the receptor extracellular domain encoded by exons 4 and 5 of the IFNAR1 gene. These results therefore indicate that different type I interferons require different subdomains of the Hu-IFN-alphaR1 receptor chain, and that the splice variant chain (Hu-IFN-alphaR1s) is functional.
Purification, Characterization, and Sequence Analysis of a Potential Virulence Factor from Porphyromonas gingivalis , Peptidylarginine Deiminase (1999)

The initiation and progression of adult-onset periodontitis has been associated with infection of the gingival sulcus by Porphyromonas gingivalis. This organism utilizes a multitude of virulence factors to evade host defenses as it establishes itself as one of the predominant pathogens in periodontal pockets. A feature common to many other oral pathogens is the production of ammonia due to its protective effect during acidic cleansing cycles in the mouth. Additionally, ammonia production by P. gingivalis has been proposed as a virulence factor due to its negative effects on neutrophil function. In this study, we describe the first purification of a peptidylarginine deiminase (PAD) from a prokaryote. PAD exhibits biochemical characteristics and properties that suggest that it may be a virulence agent. PAD deiminates the guanidino group of carboxyl-terminal arginine residues on a variety of peptides, including the vasoregulatory peptide-hormone bradykinin, to yield ammonia and a citrulline residue. The soluble protein has an apparent mass of 46 kDa, while the DNA sequence predicts a full-length protein of 61.7 kDa. PAD is optimally active at 55 degrees C, stable at low pH, and shows the greatest activity above pH 9.0. Interestingly, in the presence of stabilizing factors, PAD is resistant to limited proteolysis and retains significant activity after short-term boiling. We propose that PAD, acting in concert with arginine-specific proteinases from P. gingivalis, promotes the growth of the pathogen in the periodontal pocket, initially by enhancing its survivability and then by assisting the organism in its circumvention of host humoral defenses.
Review: Tissue engineering in the nervous system (1994)

The nervous system presents a challenge to the field of tissue engineering because some of its complex neurochemical and neuroanatomical architecture is just beginning to be understood. A combination of advances in molecular neurobiology, gene transfer techniques, and the concomitant advances in the engineering of biomaterials at a molecular level, are making tissue engineering in the nervous system possible. Due to the vast range of fields that this highly interdisciplinary task spans, any review is bound to be somewhat limited. Given that, this review attempts to cover some solutions engineered for: (a) the functional replacement of a missing neuroactive component; (b) the rescue or regeneration of degenerated neural tissue; and (c) the building of intelligent neural cell-based biosensors and simple in vitro neural circuits based on controlled neural cell attachment to electrically relevant substrates. (c) 1994 John Wiley & Sons, Inc.
Development of an Artificial Calcium-Dependent Transcription Factor To Detect Sustained Intracellular Calcium Elevation (2014)

The development of a synthetic transcription factor that responds to intracellular calcium signals enables analyzing cellular events at the single-cell level or "rewiring" the intracellular information networks. In this study, we developed the calcium-dependent transcription factor (CaTF), which was cleaved by calpain and then translocated to the nuclei where it induced reporter expression. Our results demonstrated that CaTF-mediated reporter expression was stable and responded to the intracellular calcium level and calpain activity. In addition, CaTF detected the sustained calcium increase that was induced by physiological stimulation with epidermal growth factor (EGF). These results suggest that CaTF could be a useful tool to analyze intracellular calcium signals and be an interface between an endogenous signal network and synthetic gene network.
High-Performance Immunoassays Based on Through-Stencil Patterned Antibodies and Capillary Systems (2008)

We present a simple method to pattern capture antibodies (cAbs) on poly(dimethylsiloxane) (PDMS), with high accuracy and in a manner compatible with mass fabrication for use with capillary systems (CSs), using stencils microfabricated in Si. Capture antibodies are patterned as 60−270 μm wide and 2 mm long lines on PDMS and used with CSs that have been optimized for convenient handling, pipetting of solutions, pumping of liquids, such as human blood serum, and visualization of signals for fluorescence immunoassays. With the use of this method, C-reactive protein (CRP) is detected with a sensitivity of 0.9 ng mL-1 (7.8 pM) in 1 μL of CRP-spiked human serum, within 11 min and using only four pipetting steps and a total volume of sample and reagents of 1.35 μL. This exemplifies the high performances that can be achieved using this approach and an otherwise conventional surface sandwich fluorescence immunoassay. This method is simple and flexible and should therefore be applicable to a large number of demanding immunoassays.
Determination of the activated form of the progesterone receptor (PR) in endometrial cancer (EC). (2013)

5602 Background: Endocrine treatments, in general have limited clinical efficacy in endometrial cancer. Upon ligand binding, PRs in normal tissue form discrete focal subnuclear distribution patterns (FDP), which are associated with DNA transcription. FDP are indicative of functionally activated PRs (APRs), and are observed in EC, independently of menopausal status. The feasibility of using an IHC technique to characterize the PR functional status has previously been reported in breast cancer and the APR phenotype in cell lines correlates with anti-progestin activity. The goal of this study is to determine if APR can be identified in EC and to determine if this IHC technique &amp; APR phenotype could be developed as a companion diagnostic to predict anti-progestin efficacy in patients with EC. Methods: 72 archived primary EC specimens were processed with standard IHC for estrogen receptor (ER), PR &amp; proliferation (Ki67). APR status was determined using commercially available antibodies specific to the A and B isoforms of the PR (PRA and PRB) with standard microscopy at 1000x magnification. Results: 56 (78%) tumors were of endometrioid histology. Endometrioid tumors were ER + (68%) and PR + (84%). Two PR nuclear distribution patterns were observed: an aggregated pattern (A) which is indicative of APR and a diffuse or finely granular pattern (D) indicative of an inactivated PR. This resulted in three tumor phenotypes: A cells only, D cells only, and a mix of A + D cells. APR was defined as any tumor with more than 5% A cells. An average of 49% of tumor cells were positive with PRA, 35% were positive for PRB. APR was present with PR A in 41% and with PR B in 47% of the PR + endometrioid tumors. The APR status, for both PR A and PR B, was independent of PR positivity rate, PR staining intensity score and % Ki67 positive. APR pos phenotype was associated with a lower % ER pos staining. When observable, endometrial stromal and normal cells were PR positive (D pattern). Conclusions: APR can be identified using either PRA or PRB, in ~50 % of the EC samples; there was a pattern consistent with the presence of APR positive cells. The IHC technique to identify APR has the potential to be developed as companion diagnostic as a potential predictor of anti-progestin efficacy.
Neocortical Long-Term Potentiation and Long-Term Depression: Site of Expression Investigated by Infrared-Guided Laser Stimulation (2002)

The synaptic site of expression of long-term potentiation (LTP) and long-term depression (LTD) is still a matter of debate. To address the question of presynaptic versus postsynaptic expression of neocortical LTP and LTD in a direct approach, we measured the glutamate sensitivity of apical dendrites of layer 5 pyramidal neurons during LTP and LTD. We used infrared-guided laser stimulation to release glutamate from its "caged" form with high spatial and temporal resolution. Responses to photolytically released glutamate and synaptically evoked EPSPs were recorded with patch-clamp pipettes from the neuronal somata. LTP and LTD could be induced by electrical stimulation at the same synapses in succession. The NMDA receptor-dependent LTD was accompanied by a decrease in the dendritic glutamate sensitivity, suggesting a postsynaptic expression of neocortical LTD. In contrast, LTP was never accompanied by a change in the dendritic glutamate sensitivity. A possible explanation for this finding is a presynaptic expression of neocortical LTP. Another set of experiments corroborated these results: Photolytic application of glutamate with a frequency of 5 Hz caused a long-lasting Ca2+ and NMDA receptor-dependent decrease in the dendritic glutamate sensitivity. In contrast, LTP of dendritic glutamate sensitivity was never induced by photostimulation, despite several experimental modifications to prevent washout of the induction mechanism and to induce a stronger postsynaptic Ca2+ influx. In conclusion, our findings provide strong evidence for a postsynaptic expression of neocortical LTD and favor a primarily presynaptic locus of neocortical LTP.
Cell surface glycoproteins involved in the stimulation of interleukin 1-dependent interleukin 2 production by a subline of EL4 thymoma cells. I. Functional characterization by monoclonal antibodies. (1985)

Three rat monoclonal antibodies (MAb) capable of stimulating interleukin 2 (IL 2) production by a variant subline of EL4 thymoma cells (EL4-6.1) have been produced. The stimulatory capacity of these MAb (designated RL73, RL119, and RL388) was originally found to be dependent on the presence of irradiated peritoneal exudate cells; however, this requirement could be replaced by the cellfree supernatant of the "macrophage-like" cell line P388D1 or by biochemically purified human interleukin 1 (IL 1). A number of other rat MAb directed against cell surface structures did not stimulate IL 1-dependent IL 2 production by EL4-6.1 cells; however, certain MAb directed against Thy-1 as well as the lectin phytohemagglutin did have this capacity. Furthermore, the stimulatory activity of MAb RL73, RL119, and RL388 appeared to be restricted to the EL4-6.1 variant line, because neither the parental EL4 line from which it was derived nor a series of ovalbumin-specific T-T hybrids responded to these MAb. The cell surface antigens recognized by MAb RL73, RL119, and RL388 were present on a wide variety of T cell lines and T-T hybrids, as well as on lines of B cell, macrophage, and fibroblast origin. Interestingly, the MAb reacted with the majority (approximately 85%) of thymocytes but not (or only to a very small extent) with resting T lymphocytes. After stimulation by concanavalin A, however, the three MAb reacted strongly with activated T lymphoblasts. The latter data suggest that MAb RL73, RL119, and RL388 may react with cell surface structures that are normally expressed as a consequence of lymphocyte activation.
On Packet Switches with Infinite Storage (1987)

Most prior work on congestion in datagram systems focuses on buffer management. We find it illuminating to consider the case of a packet switch with infinite storage. Such a packet switch can never run out of buffers. It can, however, still become congested. The meaning of congestion in an infinite-storage system is explored. We demonstrate the unexpected result that a datagram network with infinite storage, first-in, first-out queueing, at least two packet switches, and a finite packet lifetime will, under overload, drop all packets. By attacking the problem of congestion for the infinite-storage case, we discover new solutions applicable to switches with finite storage.
BOTULISM. STUDIES ON THE MANNER IN WHICH THE TOXIN OF CLOSTRIDIUM BOTULINUM ACTS UPON THE BODY (1923)

1. In addition to the effect upon the fibers of the parasympathetic nervous system which was described in a previous report (1), the toxin of Clostridium botilinum. Types A and B, exerts an influence upon the endings of the motor fibers of the voluntary nervous system which leads to a marked susceptibility to fatigue. It has not been determined whether the damage is in the anatomical nerve endings of the somatic motor nerve fibers or upon the myoneural junction, but it is not of the nature of an organic destruction of tissue. 2. There is no effect upon the sensory fibers of the peripheral nerves. 3. The muscle cells of the smooth and striated muscles are not affected. 4. The disturbances in function which have been demonstrated in the voluntary and involuntary nervous systems fully explain the characteristic signs and symptoms of botulinus intoxication.
Germline‐Encoded IgG Antibodies Bind Mouse Cartilage In Vivo: Epitope‐ and Idiotype‐Specific Binding and Inhibition (1994)

Autoantibodies specific for type-II collagen (CII) occur in mice and rats with collagen-induced arthritis (CIA). The binding in vitro and in vivo of mouse monoclonal antibodies (MoAbs) specific for separate epitopes in CII have been investigated. Two-day-old mice were injected intraperitoneally (i.p.) with the anti-CII antibody CIID3 in both unlabelled and biotinylated form. It was found that antibodies binding to the same epitope in CII in vivo can inhibit others from binding in an epitope-specific fashion. The binding in vivo and in vitro of anti-CII antibodies could be inhibited also by an anti-idiotypic rat antiserum produced against the D3 antibody. The anti-idiotypic antiserum inhibited the binding of the antibody D3 and the idiotypically related antibody C2. The cDNA's of anti-CII antibodies D3, C2, and F4 were sequenced and found to contain germline encoded V-genes, apparently without somatic mutations. The variable heavy chain of D3 and C2 both expressed the same VH rearrangement, confirming that they share idiotypes. This report demonstrates that CII-specific germline-encoded IgG autoantibodies bind specifically to normal cartilage in vivo via their combining site.