gebhart/patrepeval huggingface dataset:
Hematopoietic Stem Cells Need Two Signals to Prevent Apoptosis; Bcl-2 Can Provide One of These, Kitl/C-KIT Signaling the Other (2000)

Growth factors can cause cells to proliferate, differentiate, survive, or die. Distinguishing between these responses is difficult in multicellular, multiparameter systems. Yet this is essential to understand the impact on cells like hematopoietic stem cells (HSCs), which have strict and still poorly understood growth factor requirements. Single cell plating in serum-free medium allows direct assessment of growth factor responses. The range of tested factors can be expanded if the cells are protected from growth factor deprivation-induced apoptosis. BCL-2 is overexpressed in HSCs of H2K-BCL-2 transgenic mice, protecting them from many apoptotic stimuli. The response of single wild-type and transgenic HSCs to stimulations with individual factors was tested. Surprisingly, we find that high level BCL-2 expression does not prevent rapid death under serum-free conditions, even though it does in the presence of serum. We also find that transgenic, but not wild-type cells, survive and proliferate rapidly in response to steel factor (Kit ligand). These studies show that two separate signals are necessary to prevent apoptosis in HSCs, and that Kit ligand by itself provides a strong proliferative stimulus to HSCs. However, the proliferative response does not result in self-renewal, but in differentiation to all known hematopoietic oligolineage progenitors.
Convolutional face finder: a neural architecture for fast and robust face detection (2004)

In this paper, we present a novel face detection approach based on a convolutional neural architecture, designed to robustly detect highly variable face patterns, rotated up to +/-20 degrees in image plane and turned up to +/-60 degrees, in complex real world images. The proposed system automatically synthesizes simple problem-specific feature extractors from a training set of face and nonface patterns, without making any assumptions or using any hand-made design concerning the features to extract or the areas of the face pattern to analyze. The face detection procedure acts like a pipeline of simple convolution and subsampling modules that treat the raw input image as a whole. We therefore show that an efficient face detection system does not require any costly local preprocessing before classification of image areas. The proposed scheme provides very high detection rate with a particularly low level of false positives, demonstrated on difficult test sets, without requiring the use of multiple networks for handling difficult cases. We present extensive experimental results illustrating the efficiency of the proposed approach on difficult test sets and including an in-depth sensitivity analysis with respect to the degrees of variability of the face patterns.
Time-dependent outward current in guinea pig ventricular myocytes. Gating kinetics of the delayed rectifier. (1990)

Several conflicting models have been used to characterize the gating behavior of the cardiac delayed rectifier. In this study, whole-cell delayed rectifier currents were measured in voltage-clamped guinea pig ventricular myocytes, and a minimal model which reproduced the observed kinetic behavior was identified. First, whole-cell potassium currents between -10 and +70 mV were recorded using external solutions designed to eliminate Na and Ca currents and two components of time-dependent outward current were found. One component was a La3(+)-sensitive current which inactivated and resembled the transient outward current described in other cell types; single-channel observations confirmed the presence of a transient outward current in these guinea pig ventricular cells (gamma = 9.9 pS, [K]o = 4.5 mM). Analysis of envelopes of tail amplitudes demonstrated that this component was absent in solutions containing 30-100 microM La3+. The remaining time-dependent current, IK, activated with a sigmoidal time course that was well-characterized by three time constants. Nonlinear least-squares fits of a four-state Markovian chain model (closed - closed - closed - open) to IK activation were therefore compared to other models previously used to characterize IK gating: n2 and n4 Hodgkin-Huxley models and a Markovian chain model with only two closed states. In each case the four-state model was significantly better (P less than 0.05). The failure of the Hodgkin-Huxley models to adequately describe the macroscopic current indicates that identical and independent gating particles should not be assumed for this K channel. The voltage-dependent terms describing the rate constants for the four-state model were then derived using a global fitting approach for IK data obtained over a wide range of potentials (-80 to +70 mV). The fit was significantly improved by including a term representing the membrane dipole forces (P less than 0.01). The resulting rate constants predicted long single-channel openings (greater than 1 s) at voltages greater than 0 mV. In cell-attached patches, single delayed rectifier channels which had a mean chord conductance of 5.4 pS at +60 mV ([K]o = 4.5 mM) were recorded for brief periods. These channels exhibited behavior predicted by the four-state model: long openings and latency distributions with delayed peaks. These results suggest that the cardiac delayed rectifier undergoes at least two major transitions between closed states before opening upon depolarization.
DNA-mediated immunization in a transgenic mouse model of the hepatitis B surface antigen chronic carrier state. (1996)

Transgenic mice expressing the sequences coding for the envelope proteins of the hepatitis B virus (HBV) in the liver have been used as a model of the HBV chronic carrier state. We evaluated the possibility of inducing a specific immune response to the viral envelope antigens and thus potentially controlling chronic HBV infection. Using HBV-specific DNA-mediated immunization in this transgenic model, we show that the immune response induced after a single intramuscular injection of DNA resulted in the complete clearance of circulating hepatitis B surface antigen and in the long-term control of transgene expression in hepatocytes. This response does not involve a detectable cytopathic effect in the liver. Adoptive transfer of fractionated primed spleen cells from DNA-immunized mice shows that T cells are responsible for the down-regulation of HBV mRNA in the liver of transgenic mice. To our knowledge, this is the first demonstration of a potential immunotherapeutic application of DNA-mediated immunization against an infectious disease and raises the possibility of designing more effective ways of treating HBV chronic carriers.
Vocabulary Tailored Summary Generation (2018)

Neural sequence-to-sequence models have been successfully extended for summary generation.However, existing frameworks generate a single summary for a given input and do not tune the summaries towards any additional constraints/preferences. Such a tunable framework is desirable to account for linguistic preferences of the specific audience who will consume the summary. In this paper, we propose a neural framework to generate summaries constrained to a vocabulary-defined linguistic preferences of a target audience. The proposed method accounts for the generation context by tuning the summary words at the time of generation. Our evaluations indicate that the proposed approach tunes summaries to the target vocabulary while still maintaining a superior summary quality against a state-of-the-art word embedding based lexical substitution algorithm, suggesting the feasibility of the proposed approach. We demonstrate two applications of the proposed approach - to generate understandable summaries with simpler words, and readable summaries with shorter words.
Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Is Associated with Hyperinsulinemia and Insulin Resistance (2000)

High exposures of Vietnam veterans to 2,3,7, 8-Tetrachlorodibenzo-p-dioxin, a dioxin contained in the herbicide mixture Agent Orange, have previously been demonstrated to be associated with an increased prevalence of diabetes and hyperinsulinemia in non-diabetic subjects. Sixty-nine persons were identified who were in good health and had normal glucose levels during glucose tolerance testing. These subjects lived within 25 miles of the Vertac/Hercules Superfund site located in Jacksonville, Arkansas. The blood sera lipid concentrations of TCDD for the 69 subjects ranged between 2 and 94 ppt. When subjects with blood sera lipid TCDD levels in the top 10% (TCDD > 15 ppt, n = 7) were compared to subjects with lower levels (2-15 ppt, n = 62), there were no group differences in age, obesity, gender distribution, total lipids, or glucose levels. However, plasma insulin concentrations, at fasting and 30, 60, and 120 min following a 75 g glucose load, were significantly higher in the group with high blood TCDD levels. These finding could not be explained by other known risk factors for hyperinsulinemia. The finding of the TCDD-hyperinsulinemia relationship is consistent with studies of Vietnam veterans and suggests that high blood TCDD levels may cause insulin resistance.
Evaluation of a competitive ELISA method for the determination of Klebsiella O antigens (1996)

Strains of Klebsiella spp. are often inagglutinable by O-specific antisera because of the copious capsule produced by most isolates. A competitive ELISA method based on the observation that bacterial supernates containing homologous O antigen specifically inhibited the reaction of type-specific antisera with purified LPS coated on ELISA plates was used to examine the O antigen of 82 isolates of different Klebsiella species and subspecies. The O antigens O1/2ab (19 isolates), O2ab (13 isolates), O2ac (11 isolates) and O3 (16 isolates) were found to account for > 70% of the O antigenic types. Overall, 65 (79%) of the strains could be assigned to a specific O serogroup. The method is suitable for examining the role of individual O antigens in systemic klebsiella infections such as nosocomial septicaemia and pneumonia.
N-(2-hydroxybenzyl)-omega-amino carbonic acids and their derivatives as tools for biochemical and biophysical investigations. (1993)

We propose N-(2-hydroxybenzyl)-omega-amino carbonic acids (An) as multifunctional probes for fatty acid metabolism studies. Multifunctionality could be achieved by introduction of different isotopes into An molecule. Deuteration of An results in probes for 2H-NMR membrane studies. Introduction of radioactive iodine and bromine isotopes into An gives diagnosticums for gamma-tomography and PET. AnI and AnBr are fluorescence quenchers usable for membrane studies. This multifunctionality of An derivatives is valuable because they participate in such metabolic pathways of fatty acids as beta-oxidation and inclusion into lipids. They can also inhibit natural FA oxidation.
Sequence analysis of polypeptides by collision activated dissociation on a triple quadrupole mass spectrometer (1981)

A new approach to the direct sequencing of oligopeptides in complex mixtures is described. Mixtures of [2Ho]/[2H3]-N-acetylated and N,O-permethylated peptides are analyzed by collision activate dissociation on a triple quadrupole mass spectrometer using isobutane chemical ionization. Analysis of the collision activated dissociation spectra enables peptide sequences to be deduced. Use of electron capture negative chemical ionization for the sequence analysis of neuropeptides at the picomole level is also described.
Synthesis and Bio-adsorptive Properties of Large-Pore Periodic Mesoporous Organosilica Rods (2005)

Highly ordered large-pore periodic mesoporous organosilica (PMO) with a rodlike morphology was successfully synthesized at low acid concentrations and in the presence of inorganic salt using triblock copolymer P123 as a template. The inorganic salt can not only promote the formation of highly ordered mesoporous structure but also control the morphology of PMO materials. The adsorption of bovine heart cytochrome c (cyt c) on PMO was studied at different ionic strengths and pHs by comparing with the adsorption on pure silica materials with similar morphology and pore structure. The results show that the adsorbed amount reaches the maximum around the isoelectric point of cyt c and the PMO materials do not have higher adsorbed capacity than SBA-15 silica. The specific adsorption amounts of cyt c on PMO or pure silica decrease as ionic strengths increase at all pH conditions. Our results directly support the conclusion that the electrostatic interaction between cyt c and PMO/pure silica surface is more dominant than hydrophobic forces in the bioadsorption of cyt c.
Isolation and characterization of cDNA clones for rat liver 10-formyltetrahydrofolate dehydrogenase. (1991)

We have isolated and characterized cDNA clones encoding rat liver cytosol 10-formyltetrahydrofolate dehydrogenase (EC 1.5.1.6). An open reading frame of 2706 base pairs encodes for 902 amino acids of Mr 99,015. The deduced amino acid sequence contains exact matches to the NH2-terminal sequence (28 residues) and the sequences of five peptides derived from cyanogen bromide cleavage of the purified protein. The amino acid sequence of 10-formyltetrahydrofolate dehydrogenase has three putative domains. The NH2-terminal sequence (residues 1-203) is 24-30% identical to phosphoribosylglycinamide formyltransferase (EC 2.1.2.2) from Bacillus subtilis (30%), Escherichia coli (24%), Drosophila melanogaster (24%), and human hepatoma HepG2 (27%). Residues 204-416 show no extensive homology to any known protein sequence. Sequence 417-900 is 46% (mean) identical to the sequences of a series of aldehyde dehydrogenase (NADP+) (EC 1.2.1.3). Intact 10-formyltetrahydrofolate dehydrogenase exhibits NADP-dependent aldehyde dehydrogenase activity. The sequence identity to phosphoribosylglycinamide formyltransferase is discussed, and a binding region for 10-formyltetrahydrofolate is proposed.
Antigenic Drift of the Influenza A(H1N1)pdm09 Virus Neuraminidase Results in Reduced Effectiveness of A/California/7/2009 (H1N1pdm09)-Specific Antibodies (2019)

The effectiveness of influenza vaccines against circulating A(H1N1)pdm09 viruses was modest for several seasons despite the absence of antigenic drift of hemagglutinin (HA), the primary vaccine component. Since antibodies against HA and neuraminidase (NA) contribute independently to protection against disease, antigenic changes in NA may allow A(H1N1)pdm09 viruses to escape from vaccine-induced immunity. In this study, analysis of the specificities of human NA-specific monoclonal antibodies identified antigenic sites that have changed over time. The impact of these differences on <i>in vitro</i> inhibition of enzyme activity was not evident for polyclonal antisera until viruses emerged in 2013 without a predicted glycosylation site at amino acid 386 in NA. Phylogenetic and antigenic cartography demonstrated significant antigenic changes that in most cases aligned with genetic differences. Typical of NA drift, the antigenic difference is observed in one direction, with antibodies against conserved antigenic domains in A/California/7/2009 (CA/09) continuing to inhibit NA of recent A(H1N1)pdm09 viruses reasonably well. However, ferret CA/09-specific antiserum that inhibited the NA of A/Michigan/45/2015 (MI/15) very well <i>in vitro</i>, protected mice against lethal MI/15 infection poorly. These data show that antiserum against the homologous antigen is most effective and suggest the antigenic properties of NA should not be overlooked when selecting viruses for vaccine production.<b>IMPORTANCE</b> The effectiveness of seasonal influenza vaccines against circulating A(H1N1)pdm09 viruses has been modest in recent years, despite the absence of antigenic drift of HA, the primary vaccine component. Human monoclonal antibodies identified antigenic sites in NA that changed early after the new pandemic virus emerged. The reactivity of ferret antisera demonstrated antigenic drift of A(H1N1)pdm09 NA from 2013 onward. Passive transfer of serum raised against A/California/7/2009 was less effective than ferret serum against the homologous virus in protecting mice against a virus with the NA of more recent virus, A/Michigan/45/2015. Given the long-standing observation that NA-inhibiting antibodies are associated with resistance against disease in humans, these data demonstrate the importance of evaluating NA drift and suggest that vaccine effectiveness might be improved by selecting viruses for vaccine production that have NAs antigenically similar to those of circulating influenza viruses.
Biochemical Mechanisms in Inflammation (1960)

Biochemical mechanisms in inflammation , Biochemical mechanisms in inflammation , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Neutralizing Antibody Responses against Autologous and Heterologous Viruses in Acute versus Chronic Human Immunodeficiency Virus (HIV) Infection: Evidence for a Constraint on the Ability of HIV To Completely Evade Neutralizing Antibody Responses (2006)

ABSTRACT Acute human immunodeficiency virus (HIV) infection is associated with the rapid development of neutralization escape mutations. The degree to which viral evolution persists in chronic infection has not been well characterized, nor is it clear if all patients develop high-level neutralization antibody escape. We therefore measured neutralizing antibody responses against autologous and heterologous viruses in a cohort of acutely and chronically infected subjects ( n = 65). Neutralizing antibody responses against both autologous virus and heterologous viruses were lower among individuals with acute infection than among those with chronic infection. Among chronically infected individuals, there was a negative correlation between the level of neutralizing antibodies against autologous virus and the level of viremia. In contrast, there was a positive correlation between the level of neutralizing antibodies against a panel of heterologous viruses and the level of viremia. Viral evolution, as defined by the presence of higher neutralizing titers directed against earlier viruses than against contemporaneous viruses, was evident for subjects with recent infection but absent for those with chronic infection. In summary, neutralizing antibody responses against contemporaneous autologous viruses are absent in early HIV infection but can be detected at low levels in chronic infection, particularly among those controlling HIV in the absence of therapy. HIV replication either directly or indirectly drives the production of increasing levels of antibodies that cross-neutralize heterologous primary isolates. Collectively, these observations indicate that although HIV continuously drives the production of neutralizing antibodies, there may be limits to the capacity of the virus to evolve continuously in response to these antibodies. These observations also suggest that the neutralizing antibody response may contribute to the long-term control of HIV in some patients while protecting against HIV superinfection in most patients.
Liquid-to-crystal nucleation: Automated lag-time apparatus to study supercooled liquids (2001)

The statistics of liquid-to-crystal nucleation are studied using an automated lag-time apparatus. A single 500 μL sample of distilled water is repeatedly supercooled to a fixed temperature below its equilibrium freezing temperature, held until freezing occurred, and then thawed. Our raw data is then a set of approximately 300 lag-times for each of three set supercooling temperatures. In each case, a small insoluble AgI crystal was added to ensure heterogeneous nucleation and average nucleation temperatures around ΔT=8 K. The distribution of lag-times is analyzed, and shown to be well approximated by a single exponential decay, with average lag-times in the range of 1000–3000 seconds. This average lag-time decreases markedly at deeper levels of supercooling, and for the present data, this decrease is fit equally well by exponential, power law decay, and classical nucleation functional forms.
Metabotropic glutamate receptors (2008)

AC=
: adenylyl cyclase; 
DAG=
: diacylglycerol; 
FMRP=
: fragile X mental retardation protein; 
FXS=
: fragile X syndrome; 
G=
: guanine; 
GPCR=
: guanine nucleotide binding protein coupled receptor; 
GPe=
: external segment of the globus pallidus; 
GPi=
: internal segment of the globus pallidus; 
IP3=
: inositol triphosphate; 
LTD=
: long-term depression; 
LTP=
: long-term potentiation; 
mGluR=
: metabotropic glutamate receptor; 
PKC=
: protein kinase C; 
PLC=
: phospholipase C; 
SNc=
: substantia nigra pars compacta; 
SNr=
: substantia nigra pars reticulata; 
STN=
: subthalamic nucleus; 
SWD=
: spike-and-wave discharges.

Glutamate is the primary excitatory neurotransmitter in the CNS and acts via two main classes of receptors: ionotropic and metabotropic. Whereas ionotropic receptors are responsible for fast excitatory synaptic transmission, metabotropic glutamate receptors (mGluRs) have an important role in synaptic modulation throughout the CNS. Different subtypes of mGluRs regulate neuronal excitability, synaptic plasticity, neurotransmitter release, and glial functions, which are important for brain development and mechanisms of learning, injury, and neuroprotection.1–8 Not surprisingly, mGluRs have been implicated in the pathophysiology of several neurologic and psychiatric disorders, including hypoxic injury, epilepsy, Parkinson disease, Alzheimer disease, pain, anxiety, schizophrenia, and drug addiction. The development of selective non-competitive allosteric modulators of different subtypes of mGluRs allows elucidating the physiologic role of these receptors and their potential as therapeutic targets in neurologic disorders.9–11 This brief review focuses on the synaptic effects of mGluRs in some representative circuits and the potential clinical and therapeutic implications. Several publications provide a comprehensive coverage of these and related topics.1,3,5,8–16

The metabotropic receptors (mGluRs) are guanine nucleotide binding (G)-protein coupled receptors (GPCRs) that consist of dimers of subunits with seven transmembrane domains.1,2 There are eight subtypes of mGluRs that are classified, according to their structure, transduction mechanisms, and pharmacology into group I (mGluR1 and mGluR5), group II (mGlu2 and mGlu3), and group III (mGluR4, mGluR6, mGluR7, and mGluR8) receptors1–3 (table 1). Some of these receptors include several isoforms.



View this table:

Table 1 Overview of metabotropic glutamate receptors



Group I receptors (mGluR1 and mGluR5) are positively coupled to phospholipase C, and trigger calcium (Ca2+) release from the endoplasmic reticulum and activation of protein kinase C. These receptors also potentiate l-type Ca2+ channels and inhibit K+ channels. Type I mGluRs may also act independently of G proteins to activate transducing cascades that trigger phosphorylation of …
A Comparison of Phase Organization of Model Segmented Polyurethanes with Different Intersegment Compatibilities (2008)

Three series of chemically well-defined polyurethanes were synthesized with the same hard segments but different soft-segment chemistries of interest in biomedical applications. The multiblock polyurethanes have soft segments composed of either an aliphatic polycarbonate [poly(1,6-hexyl 1,2-ethyl carbonate)], polytetramethylenoxide, or a mixed macrodiol of polyhexamethylenoxide and hydroxyl-terminated poly(dimethylsiloxane) and the same hard-segment chemistry [4,4′-methylenediphenyl diisocyanate and 1,4-butanediol]. Analysis using small-angle X-ray scattering and other methods demonstrates that demixing of the hard and soft segments varies greatly between the three series of copolymers. For example, the PDMS/PHMO-based copolymers exhibit a three-phase, core−shell morphology, while the other two series exhibit a typical two-phase structure. In addition to quantitative measurements of hard/soft-segment demixing for the two-phase copolymers, FTIR spectroscopy was used to assess inter- and intracomponent hydrogen bonding, and tapping mode AFM was used to characterize the nanoscale morphology.