gebhart/patrepeval huggingface dataset:
Human monoclonal antibody HA-1A binds to endotoxin via an epitope in the lipid A domain of lipopolysaccharide (1993)

HA-1A, a human IgM mAb, has been shown to significantly reduce mortality in septic patients with Gram-negative bacteremia, especially those with septic shock, in a controlled clinical trial. To confirm the reported specificity of this antibody for the lipid A domain of endotoxin, several assay systems were developed. These assay systems included an ELISA, which measured the binding of HA-1A to lipid A adsorbed to a solid phase; a rate nephelometry assay, which measured the ability of HA-1A to bind and aggregate lipid A in solution; and a dot-blot immunoassay, which measured the ability of HA-1A to interact with lipid A adsorbed to Immobilon-P. In all three assay systems, HA-1A bound in a dose-dependent manner to lipid A prepared from Salmonella minnesota R595 LPS, whereas negative control human IgM mAb or polyclonal antibodies did not. Several experimental approaches were employed to demonstrate the specificity of HA-1A in these assay systems. Both polymyxin B and murine IgG mAb (8A1) with a specificity for lipid A were able to competitively inhibit HA-1A reactivity with lipid A in a dose-dependent manner. Furthermore, a murine IgG anti-Id mAb (9B5.5) developed against HA-1A was also able to block the binding of HA-1A to lipid A in these assay formats. HA-1A reactivity with synthetic lipid A confirmed that HA-1A binding to the natural lipid A was not the result of contaminants in the latter. Finally, the reactivity of HA-1A against a variety of glucosamine-containing and fatty acid-containing compounds was assessed. Some weak interaction was seen with cardiolipin and chitin, but not with serum proteins, lipoteichoic acid, or DNA. Collectively, these results conclusively establish that HA-1A binds to the lipid A region of LPS by an interaction with the V region of the antibody.
Surface Plasmon Resonance Imaging of Liquid Crystal Anchoring on Patterned Self-Assembled Monolayers (1997)

The anchoring of the nematic liquid crystal (LC) 4‘-n-octyl-4-cyanobiphenyl (8CB) at derivatized self-assembled monolayer (SAM) surfaces has been investigated using surface plasmon resonance (SPR) microscopy. Surfaces having distinct areas (patterns) covered by different ω-functionalized groups, one (−CF3) promoting homeotropic anchoring of the nematic director and the other (−OH) planar anchoring, were fabricated from photopatterned SAMs. Our results show that SPR microscopy, which is sensitive to the alignment on the mesoscale (i.e., within 300 nm of the interface) can be used to spatially resolve the anchoring of adsorbed LC films, with a lateral resolution on the order of a few micrometers, as a function of temperature. In addition, we observe surface melting of the crystalline phase at the SAM boundary by both homeotropic and planar aligned melts.
A Subset of β-Endorphin- or Dynorphin-Containing Neurons in the Medial Basal Hypothalamus Accumulates Estradiol (1985)

We used the combined steroid autoradiography-immunocytochemical method to determine whether estradiol- or dexamethasone-concentrating cells contain endogenous opioid peptides. Ovariectomized-adrenalectomized female rats were given highly radioactive doses of 3H-estradiol or 3H-dexamethasone, then sacrificed to demonstrate nuclear steroid binding. Autoradiograms were prepared, exposed for 2-12 months, photodeveloped, and fixed; immunocytochemistry was carried out on the same sections using antibodies to beta-endorphin or dynorphin A (1-17). In the medial basal hypothalamus, many estradiol- and some dexamethasone-concentrating neurons were found intermingled with beta-endorphin or dynorphin-immunoreactive neurons. Of the beta-endorphin-immunoreactive neurons in the medial basal hypothalamus, 4% concentrated estradiol in their nuclei. In addition, a subset of beta-endorphin-immunoreactive cells in the anterior pituitary concentrated estradiol in their nuclei. Although none of the beta-endorphin-immunoreactive neurons in the medial basal hypothalamus concentrated dexamethasone in their nuclei, many of the beta-endorphin-immunoreactive cells in the anterior pituitary did. Of the dynorphin-immunoreactive neurons in the medial basal hypothalamus, 10% concentrated estradiol in their nuclei. These data are consistent with the hypothesis of a genomic effect of estradiol on a particular subset of medial basal hypothalamic neurons that produce endogenous opioid peptides.
Gene Expression Profile of Antithrombotic Protein C Defines New Mechanisms Modulating Inflammation and Apoptosis (2001)

Human protein C is a natural anticoagulant factor, and a recombinant activated form of the molecule (rhAPC) is completing clinical evaluation for treatment of severe sepsis. Because of the pathophysiologic role of endothelial dysfunction in severe inflammatory disease and sepsis, we explored the possibility that rhAPC might directly modulate endothelial function, independent of its anticoagulant activity. Using broad transcriptional profiling, we show that rhAPC directly modulates patterns of endothelial cell gene expression clustering into anti-inflammatory and cell survival pathways. rhAPC directly suppressed expression of p50 and p52 NFkappaB subunits, resulting in a functional decrease in NFkappaB binding at target sites. Further, rhAPC blocked expression of downstream NFkappaB regulated genes following tumor necrosis factor alpha induction, including dose-dependent suppression of cell adhesion expression and functional binding of intracellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin. Further, rhAPC modulated several genes in the endothelial apoptosis pathway, including the Bcl-2 homologue protein and inhibitor of apoptosis protein. These pathway changes resulted in the ability of rhAPC to inhibit the induction of apoptosis by the potent inducer, staurosporine. This new mechanistic understanding of endothelial regulation and the modulation of tumor necrosis factor-induced endothelial dysfunction creates a novel link between coagulation, inflammation, and cell death and provides insight into the molecular basis for the efficacy of APC in systemic inflammation and sepsis.
A very sensitive microcalorimetry technique for measuring specific heat of μg single crystals (1997)

A microcalorimetry technique allowing one to measure the specific heat of bulk single crystals of a mass typically 10 μg, with a relative resolution Δc/c of 10−4 is presented. The well known ac steady state technique is employed. The sample holder is a polymer membrane with lithographically patterned thermometer and heaters made out of metallic thin films. The diameter of the useful area is 0.6 mm and the specific heat of the addendum is 1.5 μJ/K at 100 K. The sample is thermally coupled to the membrane through a gold thin film sputtered on its surface. The thermal coupling time constant of the sample is ∼5 ms, allowing to work at frequencies of 10 Hz. The method was applied to small single crystals of YBCO, providing the specific heat jump at the superconducting transition with a relative resolution of 10−2 and a precision of 10−1. The method is optimized at the temperature range 40–160 K, but can easily be modified for lower temperatures.
High-solids saccharification and viscosity studies in a scraped surface bio-reactor. (2008)

High solids processing of biomass slurries provides the following benefits: maximized product concentration in the fermentable sugar stream, reduced water usage, and reduced reactor size. However, high solids processing poses mixing and heat transfer problems above about 15% for pretreated corn stover solids due to their high viscosities. Also, highly viscous slurries require high power consumption in conventional stirred tanks since they must be run at high rotational speeds to maintain proper mixing. An 8 liter scraped surface bio-reactor (SSBR) is employed here that is designed to efficiently handle high solids loadings for enzymatic saccharification of pretreated corn stover (PCS) while maintaining power requirements on the order of low viscous liquids in conventional stirred tanks. The determination of the rheological behavior of biomass slurries is vital for process design at industrial scale. The viscosities of biomass slurries are seen here to be a function of initial solids concentration and initial biomass particle size. An extensive study has been conducted to investigate the effect of solids loading and viscosity on the rates and extent of enzymatic hydrolysis reactions. For batch testing with 25% (highest loading studied) initial PCS solids concentration, about 10% more glucose is released in the SSBR than in the shake flask after 168 hours of the saccharification reaction. The role of the viscosity of biomass slurries in power consumption of the reactor is presented. A semi-batch approach is employed to maintain lower slurry viscosity and, therefore, improved glucose release rates and reduced power consumption when operating with higher solids content. A processing efficiency is defined as sugar released per unit energy input. The 20% semi-batch saccharification test efficiency is about 27% higher than the 20% batch saccharification test efficiency. The settling of biomass particles presents a serious problem for measuring the viscosity of the slurries. Maintaining homogeneity by uniformly suspending all the particles is necessary for accurate viscosity measurements. Therefore, a new viscosity measuring technique has been developed here that incorporates the uniform suspension speed (USS) for particles in the viscometer cup that can be applied to any type of particulate suspension. The USS has been determined experimentally and computationally by a Computational Fluid Dynamics (CFD) model developed here that is well validated by experimental results. The wet density of PCS solids, which is not reported in the literature, is determined from the CFD model to be 1100 ± 50 kg/m3 based on the volume fraction distribution of
Function and heterogeneity of human Fc receptors for immunoglobulin G. (1989)

The recognition of foreign antigens by receptors on the surface of cells of the immune system is a fundamental feature of immune defenses. The receptor systems involved include the T cell receptor complex, surface Ig of B cells, class I and II histocompatibility antigens, CD4, CD8, complement recep- tors, and receptors for the Fc domain of IgG (FcYR).1 It is
Potent Fluorinated Agelastatin Analogues for Chronic Lymphocytic Leukemia: Design, Synthesis, and Pharmacokinetic Studies (2014)

Chronic lymphocytic leukemia (CLL) is the most common lymphoid neoplasia in Western societies and is currently incurable. Multiple treatment options are practiced, but the available small molecule drugs suffer from dose-limiting toxicity and undesirable side effects. The need for new, less toxic treatments is a pressing concern. Here, we demonstrate that (-)-agelastatin A (1a), a pyrrole-imidazole alkaloid obtained from a marine sponge, exhibits potent in vitro activity against primary cell lines of CLL and disclose the synthesis of several analogues that are equipotent or exceed the potency of the natural product. The novel synthetic analogue, 13-debromo-13-trifluoromethyl agelastatin A (1j), showed higher activity than the natural product when tested against the same cell lines and is the most potent agelastatin derivative reported to date. A detailed in vitro structure-activity relationship of 1a in CLL compared to that of 22 synthetic analogues is described along with preliminary in vivo pharmacokinetic and metabolism studies on the most potent compounds.
The background of INTERNIST-1 and QMR (1990)

chapter Free Access Share on The background of INTERNIST-1 and QMR Author: Jack D. Myers View Profile Authors Info & Claims A history of medical informaticsJune 1990 Pages 427–433https://doi.org/10.1145/89482.89519Published:01 June 1990Publication History 5citation21DownloadsMetricsTotal Citations5Total Downloads21Last 12 Months11Last 6 weeks2 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
TNFRSF1Bin Genetic Predisposition to Clinical Neuropathy and Effect on HDL Cholesterol and Glycosylated Hemoglobin in Type 2 Diabetes (2001)

Genetic variation in or near TNFRSF1B may predispose clinical neuropathy, reduced glycosylated hemoglobin, and increased HDL cholesterol in type 2 diabetes patients. The latter could be part of a protective response.
Tooth labeling in cone-beam CT using deep convolutional neural network for forensic identification (2017)

In large disasters, dental record plays an important role in forensic identification. However, filing dental charts for corpses is not an easy task for general dentists. Moreover, it is laborious and time-consuming work in cases of large scale disasters. We have been investigating a tooth labeling method on dental cone-beam CT images for the purpose of automatic filing of dental charts. In our method, individual tooth in CT images are detected and classified into seven tooth types using deep convolutional neural network. We employed the fully convolutional network using AlexNet architecture for detecting each tooth and applied our previous method using regular AlexNet for classifying the detected teeth into 7 tooth types. From 52 CT volumes obtained by two imaging systems, five images each were randomly selected as test data, and the remaining 42 cases were used as training data. The result showed the tooth detection accuracy of 77.4% with the average false detection of 5.8 per image. The result indicates the potential utility of the proposed method for automatic recording of dental information.
Limitation of substratum size alters cytoskeletal organization and behaviour of Swiss 3T3 fibroblasts (1989)

Cell spreading and adhesion formation in Swiss 3T3 cells was studied on circular adhesive islands of size 400-500 microns 2 made by evaporating palladium through a mask onto an underlying non-adhesive surface. Cell spreading was limited since focal contacts were restricted to the palladium. On islands less than 2000 microns 2, focal contacts and actin bundles were arranged at the cell periphery. On islands less than 1000 microns 2, the size and number of focal contacts were reduced. Focal contacts may be important regulators of proliferation, but they do not seem to form a deterministic link between substratum contact and proliferative stimulus.
Lack of chemopreventive effects of lycopene and curcumin on experimental rat prostate carcinogenesis (2001)

The chemopreventive efficacy of lycopene and curcumin with regard to prostate carcinogenesis was investigated using 3,2'-dimethyl-4-aminobiphenol (DMAB)- and 2-amino-1-methylimidazo[4,5-b]pyridine (PhIP)-induced rat ventral prostate cancer models. Three 60 week experiments with male F344 rats were carried out. In the first DMAB was given for the first 20 weeks and lycopene or curcumin were administered concomitantly or subsequently at dietary doses of 15 and 500 p.p.m., respectively. In the second experiment lycopene and curcumin were given to rats pretreated with DMAB at doses of 5, 15 or 45 p.p.m. or 100 or 500 p.p.m. In the third PhIP was selected as an initiator for prostate carcinogenesis and administered for 20 weeks. Rats were then fed a diet containing lycopene at a dose of 45 p.p.m. or curcumin at a dose of 500 p.p.m. or both together. Chemopreventive effects of lycopene and curcumin on development of DMAB-induced ventral prostate carcinomas were observed only in the first experiment and no confirmation of inhibition potential was obtained in the following studies. Neither summational nor synergistic chemoprevention was evident. It is concluded from the present data that, overall, neither lycopene nor curcumin can consistently prevent rat prostate carcinogenesis.
5‐Hydroxymethylfurfural (HMF). A Review Focussing on its Manufacture (1990)

Abstract The acid‐catalysed dehydration of hexoses results in the formation of 5‐hydroxymethylfurfural (HMF). Fructose and inulin are especially good starting materials. A review is given of the many methods to produce HMF. The reaction kinetics are dealt with in the sections: raw material, hydrolysis and reversion, catalysts, reaction temperature and time, the concentration and the risk of polymerization and the solvent and HMF stability. Manufacturing processes are illustrated for fructose as the starting material: aqueous systems with homogeneous acid catalysis or those using ion‐exchangers as catalyst, systems using dimethyl sulfoxide as the solvent and those using other organic solvents. A short treatment is given on processes starting with glucose, work up procedures and the formation of levulinic acid and other in situ ‐formed HMF‐derivatives.
\nPositional cloning of the gene for Nijmegen breakage syndrome (1998)

Nijmegen breakage syndrome (NBS), also known as ataxia-telangiectasia (AT) variant, is an autosomal recessive disorder characterized by microcephaly, growth retardation, severe combined immunodeficiency and a high incidence of lymphoid cancers. Cells from NBS patients display chromosome instability, hypersensitivity to ionizing radiation and abnormal cell-cycle regulation after irradiation, all of which are characteristics shared with AT. Recently, the NBS locus was mapped at 8q21 by two independent approaches, complementation studies and linkage analysis. Here, we report the positional cloning of the NBS gene, NBS1, from an 800-kb candidate region. The gene comprises 50 kb and encodes a protein of 754 amino acids. The amino-terminal region of the protein shows weak homology to the yeast XRS2, MEK1, CDS1 and SPK1 proteins. The gene is expressed at high levels in the testes, suggesting that it might be involved in meiotic recombination. We detected the same 5-bp deletion in 13 individuals, and conclude that it is likely to be a founder mutation.
YAP1 over‐expression in Saccharomyces cerevisiae enhances glutathione accumulation at its biosynthesis and substrate availability levels (2011)

Microbiological production of glutathione using genetically engineered yeast strains has a potential to satisfy the increasing industrial demand of this tripeptide. In the present work accumulation of glutathione in response to YAP1 over-expression in Saccharomyces cerevisiae was studied. The over-expression resulted in intracellular glutathione level over two times higher than in the parent strain. Transcript analyses revealed that, in addition to the genes encoding enzymes in the glutathione biosynthesis pathway (GSH1 and GSH2), the expression levels of the genes in the cysteine biosynthesis pathway (CYS3 and CYS4) were also significantly higher in the YAP1 over-expressed strain. This suggests that YAP1 over-expression affects glutathione accumulation at both its biosynthesis and substrate availability levels.
Ultrafast Parallelized Microfluidic Platform for Antimicrobial Susceptibility Testing of Gram Positive and Negative Bacteria (2019)

Antimicrobial susceptibility testing (AST) is an essential diagnostic procedure to determine the correct course of treatment for various types of pathogen infections. Patients are treated with broad spectrum antibiotics until AST results become available, which has contributed to the emergence of multidrug resistant bacteria worldwide. Conventional AST methods require 16-24 h to assess sensitivity of the bacteria to a given drug and establish its minimum inhibitory concentration (MIC). A rapid AST assay can assist clinicians in making an informed choice of targeted therapy and avoid unnecessary overprescription. Here, we have developed a highly parallelized droplet microfluidic platform that can screen four antibiotics/pathogens simultaneously and assess antibiotic sensitivity in 15-30 min. The device consists of four integrated microdroplet arrays, each hosting over 8000 docking sites, which can be operated individually or jointly for greater flexibility of operation. Small numbers (1-4) of bacterial cells were entrapped in droplets of 110 pL volume and monitored dynamically over 2 h. This imaging-based AST approach was used to determine the growth rates of four types of clinically relevant bacteria known to cause urinary tract infection (UTI) in millions of patients. We quantified doubling times of both Gram positive ( Staphylococcus aureus, Enterococcus faecalis) and Gram negative bacteria (e.g., Escherichia coli, Klebsiella pneumoniae) with varying levels of antibiotic resistance. Six concentrations of bactericidal and bacteriostatic antibiotics (oxacillin and tetracycline, respectively) were tested to determine the MIC of the strains as well as the heterogeneity in growth profiles of bacteria at single cell resolution. The MIC determined from phenotypic analysis in droplets matched the MIC obtained from broth microdilution method for all strains. The advantages of the proposed droplet-based AST, including rapid drug sensitivity response, morphological analysis, and heterogeneity in antibiotic-resistance profiles, make it an excellent alternative to standard phenotypic AST with potential applications in clinical diagnostics and point of care testing.
Visualization of α9 acetylcholine receptor expression in hair cells of transgenic mice containing a modified bacterial artificial chromosome (1999)

The alpha9 acetylcholine receptor (alpha9 AChR) is specifically expressed in hair cells of the inner ear and is believed to be involved in synaptic transmission between efferent nerves and hair cells. Using a recently developed method, we modified a bacterial artificial chromosome containing the mouse alpha9 AChR gene with a reporter gene encoding green fluorescent protein (GFP) to generate transgenic mice. GFP expression in transgenic mice recapitulated the known temporal and spatial expression of alpha9 AChR. However, we observed previously unidentified dynamic changes in alpha9 AChR expression in cochlear and vestibular sensory epithelia during neonatal development. In the cochlea, inner hair cells persistently expressed high levels of alpha9 AChR in both the apical and middle turns, whereas both outer and inner hair cells displayed dynamic changes of alpha9 AChR expression in the basal turn. In the utricle, we observed high levels of alpha9 AChR expression in the striolar region during early neonatal development and high levels of alpha9 AChR in the extrastriolar region in adult mice. Further, simultaneous visualization of efferent innervation and alpha9 AChR expression showed that dynamic expression of alpha9 AChR in developing hair cells was independent of efferent contacts. We propose that alpha9 AChR expression in developing auditory and vestibular sensory epithelia correlates with maturation of hair cells and is hair-cell autonomous.