gebhart/patrepeval huggingface dataset:
Adaptation to persistent growth in the H9 cell line renders a primary isolate of human immunodeficiency virus type 1 sensitive to neutralization by vaccine sera (1995)

Seven diverse primary isolates of human immunodeficiency virus type 1 (HIV-1) were examined and found to be refractory to neutralization by antisera to recombinant gp120 (rgp120) protein from HIV-1 MN. This stands in marked contrast to the sensitivity exhibited by certain laboratory-adapted viruses. To understand the difference between primary and laboratory-adapted viruses, we adapted the primary virus ACH 168.10 to growth in the FDA/H9 cell line. ACH 168.10 was chosen because the V3 region of gp120 closely matches that of MN. After 4 weeks, infection became evident. The virus (168A) replicated in FDA/H9 cells with extensive cytopathic effect but was unchanged in sensitivity to antibody-mediated neutralization. Thus, growth in cell lines is not sufficient to render primary virus sensitive to neutralization. The 168A virus was, however, partially sensitive to CD4 immunoadhesin (CD4-Ig). Adaptation was continued to produce a persistently infected FDA/H9 culture that displayed minimal cytopathic effect. The virus (168C) was now sensitive to neutralization by MN rgp120 vaccine sera and by MN-specific monoclonal antibodies and showed increased sensitivity to HIVIG and CD4-Ig. 168C encoded three amino acid changes in gp120, including one within the V3 loop (I-166-->R, I-282-->N, G-318-->R). MN-specific monoclonal antibodies bound equally to the surface of cells infected with either neutralization-resistant or -sensitive virus. The coincidence of changes in neutralization sensitivity with changes in cell tropism and cytopathic effect suggests a common underlying mechanism(s) acting through the whole of the envelope protein complex.
Highly efficient endonucleolytic cleavage of RNA by a Cys 2 His 2 zinc-finger peptide (1999)

We have identified a 30-aa peptide that efficiently cleaves single-stranded RNA. The peptide sequence corresponds to a single zinc finger of the human male-associated ZFY protein; a transcription factor belonging to the Cys(2)His(2) family of zinc-finger proteins. RNA cleavage was observed only in the absence of zinc. Coordination with zinc resulted in complete loss of ribonuclease activity. The ribonuclease active structure was determined to be a homodimeric form of the peptide. Dimerization of the peptide occurred through a single intermolecular disulfide between two of the four cystines. The observed hydrolytic activity was single-stranded RNA-specific. Single-stranded DNA, double-stranded RNA and DNA, and 2'-methoxy-modified sequences were not degraded by the peptide. The peptide specifically cleaved pyrimidines within single-stranded RNA and the dinucleotide sequence 5'-pyr-A-3' was preferred. The RNA cleavage products consisted of a 3' phosphate and 5' hydroxyl. The initial rates of cleavage (V(0)) observed for the finger peptide were comparable to rates observed for human ribonucleases, and the catalytic rate (K(cat)) was comparable to rates observed for the group II intron rybozymes. The pH profile exhibited by the peptide is characteristic of general acid-base catalytic mechanisms observed with other ribonucleases. These observations raise interesting questions about the potential biological roles of zinc-finger proteins.
Bone morphogenetic protein and retinoic acid signaling cooperate to induce osteoblast differentiation of preadipocytes (2002)

Mesenchymal cells can differentiate into osteoblasts, adipocytes, myoblasts, or chondroblasts. Whether mesenchymal cells that have initiated differentiation along one lineage can transdifferentiate into another is largely unknown. Using 3T3-F442A preadipocytes, we explored whether extracellular signals could redirect their differentiation from adipocyte into osteoblast. 3T3-F442A cells expressed receptors and Smads required for bone morphogenetic protein (BMP) signaling. BMP-2 increased proliferation and induced the early osteoblast differentiation marker alkaline phosphatase, yet only mildly affected adipogenic differentiation. Retinoic acid inhibited adipose conversion and cooperated with BMP-2 to enhance proliferation, inhibit adipogenesis, and promote early osteoblastic differentiation. Expression of BMP-RII together with BMP-RIA or BMP-RIB suppressed adipogenesis of 3T3-F442A cells and promoted full osteoblastic differentiation in response to retinoic acid. Osteoblastic differentiation was characterized by induction of cbfa1, osteocalcin, and collagen I expression, and extracellular matrix calcification. These results indicate that 3T3-F442A preadipocytes can be converted into fully differentiated osteoblasts in response to extracellular signaling cues. Furthermore, BMP and retinoic acid signaling cooperate to stimulate cell proliferation, repress adipogenesis, and promote osteoblast differentiation. Finally, BMP-RIA and BMP-RIB induced osteoblast differentiation and repressed adipocytic differentiation to a similar extent.
Macrophage Oxidation of L-Arginine to Nitric Oxide, Nitrite, and Nitrate (1989)

A new metabolic pathway characterized recently that is expressed in activated macrophages involves the formation of nitric oxide ('N = O) as an intermediate. The 'N = O formed decomposes to nitrite (NO2-) and nitrate (NO3-). The substrate for the reaction is the amino acid arginine which is oxidized at the guanido nitrogen to yield citrulline as the other product of the reaction. The studies reported here show that the activity for this unusual oxidation reaction which is contained in the 100,000 x g supernatant was lost after desalting on a Sephadex G-25 column. A small molecule cofactor was found to be required for the restoration of activity. The addition of (6R)-tetrahydrobiopterin (BH4) and NADPH led to complete recovery of activity in this desalted protein. Analysis of macrophage cell extracts, using high performance liquid chromatography with electrochemical detection, showed that BH4 was present at 17 pmol/10(6) cells or 2.1 microM in macrophage supernatant. Only the (6R)-isomer was present. With the addition of BH4 and NADPH, there was loss of arginine that was equal to the NO2-, NO3-, and citrulline formed. With substoichiometric levels of NADPH relative to BH4, the loss of arginine was greater than the formation of the end products of the reaction. A scheme for the reaction pathway consistent with the results involves N-hydroxylation of arginine as the initial step. The participation of BH4 in this type of oxidative chemistry is consistent with previous characterizations of this co-factor.
Rationale of Platelet Gel to Augment Adaptive Remodeling of the Injured Heart (2004)

Cardiac pathologic events including; myocardial infarction, viral infection and hypertrophy, and aging, may trigger maladaptive remodeling of the myocardium. Maladaptive remodeling results in diastolic and systolic dysfunction, myocyte loss, and malformation of the extracellular matrix. It is proposed that platelet gel applied to the site of myocardial injury may provide the proper cytokines, growth factors, and chemokines to promote adaptive remodeling. The hypothesis is that platelet gel concentrates may provide a temporary and local hyperphysiologic concentration of platelet secretory factors that may initiate adaptive myocardial healing. Autologous platelet gel can be derived from concentrated platelets activated and induced to secrete cytokines, growth factors, and chemokines with an array of stimulating agents. This report discusses selected platelet secretory factors, including; IL-1beta, TGF-beta, TGF-alpha, FGF, EGF, PDGF, and IGF, which support the concept that platelet concentrates can mediate cardiac wound healing. In conclusion, application of platelet gel to areas of cardiac injury may offer a therapeutic means to stimulate myocyte regeneration, angiogenesis, and restoration of a normal extracellular matrix composition.
Standards for photoluminescence quantum yield measurements in solution (IUPAC Technical Report) (2011)

The use of standards for the measurement of photoluminescence quantum yields (QYs) in dilute solutions is reviewed. Only three standards can be considered well established. Another group of six standards has been investigated by several independent researchers. A large group of standards is frequently used in recent literature, but the validity of these is less certain. The needs for future development comprise: (i) confirmation of the validity of the QY values of many commonly used standard materials, preferably in the form of SI traceable standards; (ii) extension of the set of standard materials to the UV and near-IR spectral ranges; and (iii) good standards or robust protocols for the measurements of low QYs.
Probability Theory-Based SNP Association Study Method for Identifying Susceptibility Loci and Genetic Disease Models in Human Case-Control Data (2010)

One of the most challenging points in studying human common complex diseases is to search for both strong and weak susceptibility single-nucleotide polymorphisms (SNPs) and identify forms of genetic disease models. Currently, a number of methods have been proposed for this purpose. Many of them have not been validated through applications into various genome datasets, so their abilities are not clear in real practice. In this paper, we present a novel SNP association study method based on probability theory, called ProbSNP. The method firstly detects SNPs by evaluating their joint probabilities in combining with disease status and selects those with the lowest joint probabilities as susceptibility ones, and then identifies some forms of genetic disease models through testing multiple-locus interactions among the selected SNPs. The joint probabilities of combined SNPs are estimated by establishing Gaussian distribution probability density functions, in which the related parameters (i.e., mean value and standard deviation) are evaluated based on allele and haplotype frequencies. Finally, we test and validate the method using various genome datasets. We find that ProbSNP has shown remarkable success in the applications to both simulated genome data and real genome-wide data.
Biological Activity of Retinoids Correlates with Affinity for Nuclear Receptors but Not for Cytosolic Binding Protein (1988)

In order to better understand the respective roles of the nuclear retinoic acid receptors (RARs) and the cytosolic retinoic acid binding protein (CRABP) in the mode of action of retinoic acid (RA), several types of RA analogs have been synthesized. Representative compounds have been radiolabeled to a high specific activity and their binding (direct and competition) to RARs and CRABP was determined. Their biological activity on F9 embryonal carcinoma cell differentiation has been determined by a quantitative assay of plasminogen activator (PA). All biologically active analogs studied in this work bound to RARs. A good correlation was found between PA induction and affinity for the RARs, with the exception of RA itself which was a good ligand but a moderate inducer of F9 differentiation. Two biologically active analogs (compounds II and III) did not bind to the CRABP. One biologically inactive analog (compound VIII) bound to CRABP. These results strongly suggest that retinoids must bind to RARs but not necessarily to CRABP in order to induce cell differentiation in F9 cells.
Engineering a targeted delivery platform using Centyrins (2016)

Targeted delivery of therapeutic payloads to specific tissues and cell types is an important component of modern pharmaceutical development. Antibodies or other scaffold proteins can provide the cellular address for delivering a covalently linked therapeutic via specific binding to cell-surface receptors. Optimization of the conjugation site on the targeting protein, linker chemistry and intracellular trafficking pathways can all influence the efficiency of delivery and potency of the drug candidate. In this study, we describe a comprehensive engineering experiment for an EGFR binding Centyrin, a highly stable fibronectin type III (FN3) domain, wherein all possible single-cysteine replacements were evaluated for expression, purification, conjugation efficiency, retention of target binding, biophysical properties and delivery of a cytotoxic small molecule payload. Overall, 26 of the 94 positions were identified as ideal for cysteine modification, conjugation and drug delivery. Conjugation-tolerant positions were mapped onto a crystal structure of the Centyrin, providing a structural context for interpretation of the mutagenesis experiment and providing a foundation for a Centyrin-targeted delivery platform.
Assessment of Blood Flow Through the Lung Using Laser Doppler Flowmetry (1991)

The value of laser Doppler flowmetry in measuring blood flow through the lung was assessed comparing it with flow measured by electromagnetic flowmetry. This was an experimental laboratory-based prospective study performed in an approved University animal research facility. Ten beagle dogs were used. Simultaneous measurement of pulmonary blood flow by laser Doppler flowmetry and electromagnetic flowmetry was carried out at varying degrees of pulmonary artery constriction. There was a linear relationship between the two methods of assessing blood flow (regression equation: y = 0.9x + 5.5; p = .00001) using a least-squares, best fit, straight line analysis (160 data points). The results of this study demonstrate that laser Doppler flowmetry provides an accurate indicator of pulmonary blood flow, which in practice is both simple and reproducible.
Candidate 'Gene Silencers' Found (1999)

Sometimes genes don't add up. About a decade ago, researchers added additional copies of pigment genes to petunias, hoping to darken their purple flowers. Instead, the petals turned white. Biologists now know that in many organisms, including plants, worms, and flies, adding an extra dose of a gene can have the paradoxical effect of slashing that gene's expression. This phenomenon, which goes by the name posttranscriptional gene silencing (PTGS) and helps organisms defend themselves against viral and other foreign nucleic acids, occurs because the added gene somehow causes destruction of the messenger RNA (mRNA) made by both it and the corresponding cellular gene. As a result, production of the gene's protein product shuts down. Now, researchers may have found the tracking system that homes in on the mRNA and triggers its destruction.
Lithium Trifluoromethanesulfonate (LiOTf) as a Recyclable Catalyst for Highly Efficient Acetylation of Alcohols and Diacetylation of Aldehydes under Mild and Neutral Reaction Conditions (2003)

A variety of alcohols and aldehydes were reacted with acetic anhydride at room temperature in the presence of a catalytic amount of lithium triflate (LiOTf) to produce the corresponding esters and 1,1-diacetates, respectively, in good to excellent yields under essentially neutral reaction conditions. Sensitive functional groups such as PhCO(2)-, OMe, and OTBDMS ethers survived intact under the described reaction conditions.
Identification and characterization of a basic cell surface-located protein from Lactobacillus fermentum BR11 (1997)

Extraction of Lactobacillus fermentum BR11 cells with 5 M LiCl yielded a preparation containing a single predominant polypeptide with an apparent molecular mass of 32 kDa. A clone encoding an immunoreactive 32-kDa polypeptide was isolated from a pUC18 library of L. fermentum BR11 DNA by screening with an antiserum raised against whole cells of L. fermentum BR11. Sequence determination of the insert in the clone revealed a complete 795-bp open reading frame (ORF) that defines a 28,625-Da polypeptide (BspA). N-terminal sequencing of the LiCl-extracted polypeptide from L. fermentum BR11 confirmed that it is the same as the cloned BspA. BspA was found to have a sequence similar to those of family III of the bacterial solute-binding proteins. The sequences of two ORFs upstream of bspA are consistent with bspA being located in an operon encoding an ATP-binding cassette-type uptake system. Unusually, BspA contains no lipoprotein cleavage and attachment motif (LXXC), despite its origin in a gram-positive bacterium. Biotin labelling and trypsin digestion of whole cells indicated that this polypeptide is exposed on the cell surface. The isoelectric point as predicted from the putative mature sequence is 10.59. It was consequently hypothesized that the positively charged BspA is anchored by electrostatic interaction with acidic groups on the cell surface. It was shown that BspA could be selectively removed from the surface by extraction with an acidic buffer, thus supporting this hypothesis.
ELISA for the measurement of serum and urinary chorionic gonadotropin concentrations in the laboratory macaque (1997)

A rapid, sensitive, enzyme-linked immunosorbant assay (ELISA) for the measurement of chorionic gonadotropin (CG) in serum and urine samples of laboratory macaques is reported. The ligand (CG) is captured by a readily available, widely used, and well-characterized monoclonal antibody (Mab, 518B7) generated against the beta subunit of bovine luteinizing hormone (LH). This Mab, while specific for LH, shows very little species specificity, and has been shown to detect LH and CG by radioimmunoassay (RIA) in both human and non-human primates. A polyclonal antiserum raised in rabbits against human chorionic gonadotropin (hCG) is conjugated to horseradish peroxidase, and is used as the second antibody signal. This anti-hCG antiserum cross reacts with CG secreted by both the human (hCG) and macaque (mCG). The ELISA utilizes hCG as the standard, and results are based on the relative concentrations of mCG in serum and urine. Total assay time is less than 5 hours. Range of the standard curve is 0.002 to 0.5 ng hCG/well, and the least detectable concentration of hCG is 0.0023 +/- 0.0007 ng/well. Pregnancy was detected in early pregnant macaques (M. fascicularis) on 9 (N = 1/16), 10 (N = 1/16), 11 (N = 1/16), 12 (N = 6/16), 13 (N = 1/16), 14 (N = 4/16), and 15 (N = 2/16) days following the pre-ovulatory urinary estrone conjugate peak. The detection of pregnancy by urinary mCG occurred approximately 24 to 72 hours after its detection in serum.
Hypoxia-induced pulmonary vascular remodeling: a model for what human disease? (2000)

Exposure of most animals to low levels of environmental oxygen results in alveolar hypoxia and reliably causes chronic pulmonary hypertension and morphological alterations of the precapillary pulmonary vessels (1-4). Chronic hypoxic exposure of animals has been used for decades to induce pulmonary vascular remodeling and, more recently, to assess the roles in this process of lipid mediators (5), endothelin (6), serotonin (7), nitric oxide (NO) (8, 9), and prostacyclin (10), as well as VEGF and its receptors As one measure of the clinical importance of work in this system, trials are now ongoing to test endothelin receptor blockers in the treatment of severe pulmonary hypertension.
Catalytic Promiscuity in Biocatalysis: Using Old Enzymes to Form New Bonds and Follow New Pathways (2004)

Biocatalysis has expanded rapidly in the last decades with the discoveries of highly stereoselective enzymes with broad substrate specificity. A new frontier for biocatalysis is broad reaction specificity, where enzymes catalyze alternate reactions. Although often under-appreciated, catalytic promiscuity has a natural role in evolution and occasionally in the biosynthesis of secondary metabolites. Examples of catalytic promiscuity with current or potential applications in synthesis are reviewed here. Combined with protein engineering, the catalytic promiscuity of enzymes may broadly extend their usefulness in organic synthesis.
Sensorless Control of Induction Motor Drives Equipped With Inverter Output Filter (2006)

This paper deals with the speed sensorless vector control of an induction motor in a special case where the output voltage of the pulsewidth-modulated inverter is filtered by an inductance-capacitance (LC) filter. The system states are estimated by means of an adaptive full-order observer, and no additional voltage, current, or speed measurements are needed. The rotor speed adaptation is based on the estimation error of the inverter output current. Quasi-steady-state and linearization analyses are used to design an observer that enables a wide operation region, including very low and very high speeds. A torque-maximizing control method is applied in the field-weakening region. Simulation and experimental results show that the performance is comparable to that of a drive without the LC filter
Myotonic dystrophy type 1 is associated with nuclear foci of mutant RNA, sequestration of muscleblind proteins and deregulated alternative splicing in neurons (2004)

Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG repeat in the DMPK gene. In skeletal muscles, DM1 may involve a novel, RNA-dominant disease mechanism in which transcripts from the mutant DMPK allele accumulate in the nucleus and compromise the regulation of alternative splicing. Here we show evidence for a similar disease mechanism in brain. Examination of post-mortem DM1 tissue by fluorescence in situ hybridization indicates that the mutant DMPK mRNA, with its expanded CUG repeat in the 3'-untranslated region, is widely expressed in cortical and subcortical neurons. The mutant transcripts accumulate in discrete foci within neuronal nuclei. Proteins in the muscleblind family are recruited into the RNA foci and depleted elsewhere in the nucleoplasm. In parallel, a subset of neuronal pre-mRNAs show abnormal regulation of alternative splicing. These observations suggest that CNS impairment in DM1 may result from a deleterious gain-of-function by mutant DMPK mRNA.
Versatile low power media access for wireless sensor networks (2004)

We propose <i>B-MAC</i>, a carrier sense media access protocol for wireless sensor networks that provides a flexible interface to obtain ultra low power operation, effective collision avoidance, and high channel utilization. To achieve low power operation, <i>B-MAC</i> employs an adaptive preamble sampling scheme to reduce duty cycle and minimize idle listening. <i>B-MAC</i> supports on-the-fly reconfiguration and provides bidirectional interfaces for system services to optimize performance, whether it be for throughput, latency, or power conservation. We build an analytical model of a class of sensor network applications. We use the model to show the effect of changing <i>B-MAC</i>'s parameters and predict the behavior of sensor network applications. By comparing <i>B-MAC</i> to conventional 802.11-inspired protocols, specifically SMAC, we develop an experimental characterization of <i>B-MAC</i> over a wide range of network conditions. We show that <i>B-MAC</i>'s flexibility results in better packet delivery rates, throughput, latency, and energy consumption than S-MAC. By deploying a real world monitoring application with multihop networking, we validate our protocol design and model. Our results illustrate the need for flexible protocols to effectively realize energy efficient sensor network applications.
The renal renin-angiotensin system (2009)

The renin-angiotensin system (RAS) is a critical regulator of sodium balance, extracellular fluid volume, vascular resistance, and, ultimately, arterial blood pressure. In the kidney, angiotensin II exerts its effects to conserve salt and water through a combination of the hemodynamic control of renal blood flow and glomerular filtration rate and tubular epithelial cell sodium chloride and water transport mechanisms. Pharmacological inhibition of the actions of the RAS are widely used in the treatment of patients with hypertension, congestive heart failure, left ventricular dysfunction, pulmonary and systemic edema, diabetic nephropathy, cirrhosis of the liver, scleroderma, and migraines. Therefore, a thorough understanding of the influences of the RAS on normal renal physiology is of major importance for first-year medical students.