gebhart/patrepeval huggingface dataset:
Effects of methylation on a synthetic polynucleotide: the B--Z transition in poly(dG-m5dC).poly(dG-m5dC). (1981)

We have compared the behavior in solution of the synthetic polynucleotide poly(dG-m5dC).poly(dG-m5dC) with that of the unmethylated polynucleotide poly(dG-dC).poly(dG-dC). In solutions containing high concentrations of salt, poly(dG-dC).poly(dG-dC) is known to exhibit altered circular dichroic and absorption spectra correlated with formation of a left-handed Z DNA structure. Poly(dG-m5dC).poly(dG-m5dC) behaves similarly, but the spectral transition from the B to the Z form occurs at much lower salt concentrations, close to usual physiological conditions. Divalent and polyvalent ions are particularly effective: The B--Z transition of poly(dG-m5dC).(dG-m5dC) can be induced at a Mg2+ concentration three orders of magnitude lower than that required for the unmethylated polymer. We have also studied mixed copolymers containing both dC and m5dC. Our results suggest that the sequence m5dC-dG, which occurs in eukaryotic DNA, can have a disproportionately large effect on the B--Z transition.
Requirements for Internet gateways (1987)

This document is a formal statement of the requirements to be met by gateways used in the Internet system.As such, it is an official specification for the Internet community.Distribution of this memo is unlimited.This RFC summarizes the requirements for gateways to be used between networks supporting the Internet protocols.While it was written specifically to support National Science Foundation research programs, the requirements are stated in a general context and are applicable throughout the Internet
PEGylation Confers Greatly Extended Half-Life and Attenuated Immunogenicity to Recombinant Methioninase in Primates (2004)

Methionine depletion by recombinant methioninase (rMETase) has been demonstrated previously to be highly effective in tumor-bearing mouse models. However, the therapeutic potential of rMETase has been limited by its short plasma half-life and immunologic effects, including high antibody production in mice and monkeys and anaphylactic reactions in monkeys. To overcome these limits of rMETase, the enzyme has been coupled to methoxypolyethylene glycol succinimidyl glutarate (MEGC-PEG-5000). In this study, we evaluated the pharmacokinetics, antigenicity and toxicity of MEGC-PEG-rMETase in Macaca fascicularis monkeys using an escalating-dose strategy. Dose ranging studies at 1,000, 4,000, and 8,000 units/kg i.v. determined that a single dose of 4,000 units/kg was sufficient to reduce plasma methionine to <5 micromol/L for 12 hours. Pharmacokinetic analysis with the single 4,000 units/kg dose showed that MEGC-PEG-rMETase holoenzyme activity was eliminated with a biological half-life of 1.3 hours, and the MEGC-PEG-rMETase apoenzyme was eliminated with a biological half-life of 90 hours, an approximately 36-fold increase compared with non-PEGylated rMETase. A single dose at 2,000 units/kg of MEGC-PEG-rMETase resulted in an apoenzyme half-life of 143 hours. A seven-day i.v. administration of 4,000 units/kg every 12 hours resulted in a steady-state depletion of plasma methionine to <5 micromol/L. The only manifest toxicity was decreased food intake and slight weight loss. Red cell values and hemoglobin declined transiently during treatment but recovered after cessation of treatment. Subsequent challenges on days 29, 50 and, 71 did not result in any immunologic reactions. This result is in contrast to non-PEGylated rMETase, which elicited anaphylactic reactions in monkeys. Anti-MEGC-PEG-rMETase antibodies (at 10(-2)) were found on day 29, and these increased to 10(-3) to 10(4) on day 71, 100 to 1,000-fold less than antibodies elicited by naked rMETase. Although anti-MEGC-PEG-rMETase antibodies were produced, no neutralizing antibody was identified, and each challenge dose was effective in depleting plasma methionine levels. The results of the present study demonstrate that PEGylation greatly prolongs serum half-life of the rMETase apoenzyme and eliminated anaphylactic reactions. The results indicate a profile with respect to serum half-life, toxicity, and antigenicity that suggest clinical potential of MEGC-PEG-rMETase.
Development of Human Cloned Blastocysts Following Somatic Cell Nuclear Transfer with Adult Fibroblasts (2008)

Nuclear transfer stem cells hold considerable promise in the field of regenerative medicine and cell-based drug discovery. In this study, a total of 29 oocytes were obtained from three young (20-24 years old) reproductive egg donors who had been successful in previous cycles. These oocytes, deemed by intended parents to be in excess of their reproductive needs, were donated for research without financial compensation by both the egg donor and intended parents after receiving informed consent. All intended parents successfully achieved ongoing pregnancies with the oocytes retained for reproductive purposes. Mature oocytes, obtained within 2 hours following transvaginal aspiration, were enucleated using one of two methods, extrusion or aspiration, after 45 minutes of incubation in cytochalasin B. Rates of oocyte lysis or degeneration did not differ between the two methods. Somatic cell nuclear transfer (SCNT) embryos were constructed using two established adult male fibroblast lines of normal karyotype. High rates of pronuclear formation (66%), early cleavage (47%), and blastocyst (23%) development were observed following incubation in standard in vitro fertilization culture media. One cloned blastocyst was confirmed by DNA and mitochondrial DNA fingerprinting analyses, and DNA fingerprinting of two other cloned blastocysts indicated that they were also generated by SCNT. Blastocysts were also obtained from a limited number of parthenogenetically activated oocytes. This study demonstrates, for the first time, that SCNT can produce human blastocyst-stage embryos using nuclei obtained from differentiated adult cells and provides new information on methods that may be needed for a higher level of efficiency for human nuclear transfer.
Toward Proteomics in Uroscopy: Urinary Protein Profiles after Radiocontrast Medium Administration (2001)

Previous attempts to use urinary protein profiles for diagnostic purposes have been rather disappointing with respect to their clinical validity, in part because of the insufficient reproducibility, sensitivity, and rapidity of available techniques. Therefore, a newly developed, high-throughput technique, namely surface-enhanced laser desorption/ionization (SELDI) ProteinChip array-time of flight mass spectrometry, was studied, to assess its applicability for protein profiling of urine and to exemplify its use for a group of patients receiving radiocontrast medium. Assessment of the accuracy, sensitivity, and reproducibility of SELDI in test urinary protein profiling was performed. Renal function was studied in 20 male Sprague-Dawley rats before and after intravenous administration of either 1.25 g/kg ioxilan (n = 10) or hypertonic saline solution (n = 10) as a control. Urine samples from 25 patients undergoing cardiac catheterization were obtained before, immediately after, and 6 to 12 h after the procedure. Administration of ioxilan to rats resulted in changes in the abundance of proteins of 9.9, 18.7, 21.0, and 66.3 kD. For patients, even in uncomplicated cases of radiocontrast medium infusion during cardiac catheterization, perturbations in the protein composition occurred but returned to baseline values after 6 to 12 h. Proteins with molecular masses of 9.75, 11.75, 23.5, and 66.4 kD changed in abundance. For patients with impaired renal function, these changes were not reversible within 6 to 12 h. As a proof of principle, one of the peaks, i.e., that at 11.75 kD, was identified as beta(2)-microglobulin. SELDI is a promising tool for the detection, identification, and characterization of trace amounts of proteins in urine. Even for patients without renal complications, proteins with a broad range of molecular masses either appear in or disappear from the urine. Some of these might represent markers of impending nephropathy.
The Relation between Serum Albumin Levels and Risk of Coronary Heart Disease in the Multiple Risk Factor Intervention Trial (1991)

The relation between serum albumin levels and subsequent incidence of myocardial infarction and coronary heart disease deaths was evaluated using stored serum from the Multiple Risk Factor Intervention Trial (MRFIT). There were 91 coronary heart disease deaths, 113 myocardial infarction patients, and 405 controls matched to cases within 5 years of age, treatment group, and clinic site. There was a highly significant inverse relation between serum albumin level and risk of coronary heart disease. Individuals with a baseline level of serum albumin greater than or equal to 4.7 g/dl had an odds ratio of 0.45 as compared with individuals with a baseline level of serum albumin less than 4.4 g/dl. The relation persisted after adjusting for other cardiovascular risk factors (blood pressure, smoking, and serum cholesterol). The association was stronger for coronary heart disease deaths than for surviving myocardial infarction patients, and for cigarette smokers as compared with cigarette nonsmokers. The deaths studied occurred in the time period at least 6 years after the sera had been obtained and up to 10.5 years of follow-up, and the myocardial infarctions studied occurred within the first 6.5 years of follow-up. There was no consistent relation between time and death due to coronary heart disease or myocardial infarction and albumin levels. Albumin levels are related to the acute phase reaction. Lower albumin levels may be a marker of persistent injury to arteries and progression of atherosclerosis and thrombosis. The consistent relation between albumin and coronary heart disease risk requires further evaluation.
Intramolecular Diels–Alder chemistry of pyrroles (1984)

The 1-pyrrolyl fumarate (5), prepared by condensation of 1-hydroxypyrrole (1a) with trans-3-(methoxycarbonyl)-acryloyl chloride (4), undergoes a facile interamolecular Diels–Alder reaction to give the product (6), the first intramolecular cycloaddition of a pyrrole.
Patterns of Gene Expression Reveal a Temporally Orchestrated Wound Healing Response in the Injured Spinal Cord (2004)

Spinal cord injury (SCI) induces a progressive pathophysiology affecting cell survival and neurological integrity via complex and evolving molecular cascades whose interrelationships are not fully understood. The present experiments were designed to: (1) determine potential functional interactions within transcriptional expression profiles obtained after a clinically relevant SCI and (2) test the consistency of transcript expression after SCI in two genetically and immunologically diverse rat strains characterized by differences in T cell competence and associated inflammatory responses. By interrogating Affymetrix U34A rat genome GeneChip microarrays, we defined the transcriptional expression patterns in midcervical contusion lesion sites between 1 and 90 d postinjury of athymic nude (AN) and Sprague Dawley (SD) strains. Stringent statistical analyses detected significant changes in 3638 probe sets, with 80 genes differing between the AN and SD groups. Subsequent detailed functional categorization of these transcripts unveiled an overall tissue remodeling response that was common to both strains. The functionally organized gene profiles were temporally distinct and correlated with repair indices observed microscopically and by magnetic resonance microimaging. Our molecular and anatomical observations have identified a novel, longitudinal perspective of the post-SCI response, namely, that of a highly orchestrated tissue repair and remodeling repertoire with a prominent cutaneous wound healing signature that is conserved between two widely differing rat strains. These results have significant bearing on the continuing development of cellular and pharmacological therapeutics directed at tissue rescue and neuronal regeneration in the injured spinal cord.
Biomedical applications of 10B and 11B NMR (2005)

This review focuses mainly on the detection and investigation of molecules used for boron neutron capture therapy (BNCT) by 10B and 11B NMR. In this binary radiation treatment, boron-containing molecules (also called 'BNCT agents') enriched in the 10B isotope, are targeted to the tumor, and irradiated with thermal or epithermal neutrons. Capture of these neutrons by 10B nuclei generates cell-damaging radiation, confined to single cell dimensions. NMR research efforts have primarily been applied in two directions: first, to investigate the metabolism and pharmaco-kinetics of BNCT agents in-vivo, and second, to use localized NMR spectroscopy and/or MRI for non-invasive mapping of the administered molecules in treated animals or patients. While the first goal can be pursued using 11B NMR for natural-abundance samples (80% 11B / 20% 10B), molecules used in the actual treatment are > 95% enriched in 10B, and must therefore be detected by 10B NMR. Both 10B (spin 3) and 11B (spin 3/2) are quadrupolar nuclei, and their typical relaxation times, in common BNCT agents in biological environments, are rather short. This poses some technical challenges, particularly for MRI, which will be reviewed, along with possible solutions. The first attempts at 11B NMR and MRI detection of BNCT agents in biological tissue were conducted over a decade ago. Since then, results from 11B MRI in laboratory animals and in humans have been reported, and 11B NMR spectroscopy provided interesting and unique information about the metabolism of some BNCT agents in cultured cells. 10B NMR was applied either 'indirectly' (in double-resonance experiments involving coupled protons), but also by direct 10B MRI in mice. However, no results involving the NMR detection of 10B-enriched compounds in treated patients have been reported yet.
Structure of sortase, the transpeptidase that anchors proteins to the cell wall of Staphylococcus aureus (2001)

Surface proteins of Gram-positive bacteria play important roles during the pathogenesis of human infections and require sortase for anchoring to the cell-wall envelope. Sortase cleaves surface proteins at the LPXTG motif and catalyzes the formation of an amide bond between the carboxyl group of threonine (T) and the amino group of cell-wall crossbridges. The NMR structure of sortase reveals a unique beta-barrel structure, in which the active-site sulfhydryl of cysteine-184 is poised for ionization by histidine-120, presumably enabling the resultant thiolate to attack the LPXTG peptide. Calcium binding near the active site stimulates catalysis, possibly by altering the conformation of a surface loop that recognizes newly translocated polypeptides. The structure suggests a mechanistic relationship to the papain/cathepsin proteases and should facilitate the design of new antiinfective agents.
Ge-on-SOI-Detector/Si-CMOS-Amplifier Receivers for High-Performance Optical-Communication Applications (2007)

In this paper, an overview and assessment of high-performance receivers based upon Ge-on-silicon-on-insulator (Ge-on-SOI) photodiodes and Si CMOS amplifier ICs is provided. Receivers utilizing Ge-on-SOI lateral p-i-n photodiodes paired with high-gain CMOS amplifiers are shown to operate at 15 Gb/s with a sensitivity of -7.4 dBm (BER=10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-12</sup> ) while utilizing a single supply voltage of only 2.4 V. The 5-Gb/s sensitivity of similar receivers is constant up to 93 degC, and 10-Gb/s operation is demonstrated at 85 degC. Error-free (BER<10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-12</sup> ) operation of receivers combining a Ge-on-SOI photodiode with a single-ended high-speed receiver front end is demonstrated at 19 Gb/s, using a supply voltage of 1.8 V. In addition, receivers utilizing Ge-on-SOI photodiodes integrated with a low-power CMOS IC are shown to operate at 10 Gb/s using a single 1.1-V supply while consuming only 11 mW of power. A perspective on the future technological capabilities and applications of Ge-detector/Si-CMOS receivers is also provided
[Isolation and partial characterization of EGF-like growth factor from rat glioma tissue]. (1987)

Using acid-ethanol extraction, two proteins with Mr=8 and 12 kD were extracted from rat glioma tissue induced with ethylnitrosourea. These proteins were shown to complete for the receptor with [125I]EGF (epidermal growth factor) on A431 cells. The 8 kD protein exhibited a marked mitogenic effect by stimulating DNA synthesis in resting NIH 3T3 cells. Stepwise chromatography of the acid-ethanol extract on Biogels P-60 and P-10 resulted in preparative amounts of the protein and allowed for its partial characterization. It was found that the half-maximum stimulation of DNA synthesis in NIH 3T3 cells was achieved at growth factor protein concentration of 5 micrograms/ml. The preparation obtained possessed the EGF-competing activity of 10 ng-equiv. EGF per 1 microgram of protein and stimulated protein phosphorylation of the 170 kD protein in NRK cell membranes. The data obtained suggest that this factor may be related to the family of the so-called EGF-like growth factors.
Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes. (1989)

The analysis of DNA for the presence of particular mutations or polymorphisms can be readily accomplished by differential hybridization with sequence-specific oligonucleotide probes. The in vitro DNA amplification technique, the polymerase chain reaction (PCR), has facilitated the use of these probes by greatly increasing the number of copies of target DNA in the sample prior to hybridization. In a conventional assay with immobilized PCR product and labeled oligonucleotide probes, each probe requires a separate hybridization. Here we describe a method by which one can simultaneously screen a sample for all known allelic variants at an amplified locus. In this format, the oligonucleotides are given homopolymer tails with terminal deoxyribonucleotidyltransferase, spotted onto a nylon membrane, and covalently bound by UV irradiation. Due to their long length, the tails are preferentially bound to the nylon, leaving the oligonucleotide probe free to hybridize. The target segment of the DNA sample to be tested is PCR-amplified with biotinylated primers and then hybridized to the membrane containing the immobilized oligonucleotides under stringent conditions. Hybridization is detected nonradioactively by binding of streptavidin-horseradish peroxidase to the biotinylated DNA, followed by a simple colorimetric reaction. This technique has been applied to HLA-DQA genotyping (six types) and to the detection of Mediterranean beta-thalassemia mutations (nine alleles).
Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. (1999)

Oxidative stress and oxidative damage to tissues are common end points of chronic diseases, such as atherosclerosis, diabetes, and rheumatoid arthritis. The question addressed in this review is whether increased oxidative stress has a primary role in the pathogenesis of diabetic complications or whether it is a secondary indicator of end-stage tissue damage in diabetes. The increase in glycoxidation and lipoxidation products in plasma and tissue proteins suggests that oxidative stress is increased in diabetes. However, some of these products, such as 3-deoxyglucosone adducts to lysine and arginine residues, are formed independent of oxidation chemistry. Elevated levels of oxidizable substrates may also explain the increase in glycoxidation and lipoxidation products in tissue proteins, without the necessity of invoking an increase in oxidative stress. Further, age-adjusted levels of oxidized amino acids, a more direct indicator of oxidative stress, are not increased in skin collagen in diabetes. We propose that the increased chemical modification of proteins by carbohydrates and lipids in diabetes is the result of overload on metabolic pathways involved in detoxification of reactive carbonyl species, leading to a general increase in steady-state levels of reactive carbonyl compounds formed by both oxidative and nonoxidative reactions. The increase in glycoxidation and lipoxidation of tissue proteins in diabetes may therefore be viewed as the result of increased carbonyl stress. The distinction between oxidative and carbonyl stress is discussed along with the therapeutic implications of this difference.
Clinical implications of recurrent gene mutations in acute myeloid leukemia (2020)

Acute myeloid leukemia (AML) is a genetically heterogeneous clonal malignancy characterized by recurrent gene mutations. Genomic heterogeneity, patients' individual variability, and recurrent gene mutations are the major obstacles among many factors that impact treatment efficacy of the AML patients. With the application of cost- and time-effective next-generation sequencing (NGS) technologies, an enormous diversity of genetic mutations has been identified. The recurrent gene mutations and their important roles in acute myeloid leukemia (AML) pathogenesis have been studied extensively. In this review, we summarize the recent development on the gene mutation in patients with AML.
Pairwise alignment using HMMs (1998)

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Expression and processing of human immunodeficiency virus type 1 gp160 using the vesicular stomatitis virus New Jersey serotype vector system (2009)

The Indiana serotype of vesicular stomatitis virus (VSV(IND)), but not the New Jersey serotype (VSV(NJ)), has been widely used as a gene expression vector. In terms of prime-boost-based vaccine strategies, it would be desirable to use two different VSV serotypes to avoid immunity against the priming viral vector. Here, we report that we have applied the VSV(NJ) vector system for expression of the env gene of human immunodeficiency virus type 1 (HIV-1). The HIV-1 env gene was inserted into the VSV(NJ) vector system at two different sites: between the P and M genes (NP-gp160-MGL) and between the G and L genes (NPMG-gp160-L). The HIV-1 env gene product, gp160, was efficiently expressed and processed in cells infected with either of these two recombinant VSV-HIV-1(gp160) viruses. In this study, we have investigated the applicability of the VSV(NJ) vector system for foreign gene expression.
Mondrian (1993)

Mondrian is an object-oriented graphical editor that can learn new graphical procedures through programming by demonstration. A user can demonstrate a sequence of graphical editing commands on a concrete example to illustrate how the new procedure should work. An interface agent records the steps of the procedure in a symbolic form, using machine learning techniques, tracking relationships between graphical objects and dependencies among the interface operations. The agent generalizes a program that can then be used on “analogous” examples. The generalization heuristics set it apart from conventional “macros” that can only repeat an exact sequence of steps. The system represents user-defined operations using pictorial “storyboards” of examples. By bringing the power of procedural programming to easy-to-use graphical interfaces, we hope to break down the “Berlin Wall” that currently exists between computer users and computer programmers.