gebhart/patrepeval huggingface dataset:
Imminent Commercialization of Sexed Bovine Sperm (1999)

Cattle breeders demand products and services that improve efficiency and maximize profits. Research and development for these products, once done primarily in academic settings, now is occurring more within the private corporate sector who now fund research that was previously funded from public sources. These products often are patented and licensed to individual companies. Product availability is hastened, but sometimes at higher costs. Sex-specific sperm soon will be available to the cattle industry for use in high profile, genetically elite herds. Widespread availability of sex-specific sperm for commercial herds should follow within 2 years. Sex-specific sperm for use with artificial insemination (AI) will enable producers to pre-determine the sex of calves from specific genetic matings, resulting in faster genetic gain within herds. This technology will reduce numbers of unwanted dairy bull calves that currently end up as dairy beef. Efficacious use of sex-specific sperm depends upon increased genetic merit and/or phenotypic gain for production traits, and increased economic efficiency of genetically superior females by the production of specific sex offspring. Managerial gains also will be realized with accurately predicted calf sex. Hair color, milk production and rate of gain are examples of many traits determined by genetic code contained in the DNA (deoxyribonucleic acid). DNA, which is organized in packets called chromosomes, specifies what each cell does and when. Bovine sperm contain 30 chromosomes, one of which is the sex chromosome. Sex is determined by X- (female) or Y- (male) chromosome-bearing sperm. In mammalians, more DNA is contained within the X-chromosome (Table 1); for bulls, X-chromosome-bearing sperm have 3.8% more DNA content than Y-chromosome-bearing sperm. This forms the basis for separating sperm via flow cytometry/sperm sorting. DNA content is the only reliably proven difference between X- and Y-chromosome-bearing sperm (Johnson and Welch, 1999).
CD62L+ NKT cells have prolonged persistence and antitumor activity in vivo (2016)

Vα24-invariant natural killer T cells (NKTs) localize to tumors and have inherent antitumor properties, making them attractive chimeric antigen receptor (CAR) carriers for redirected cancer immunotherapy. However, clinical application of CAR-NKTs has been impeded, as mechanisms responsible for NKT expansion and the in vivo persistence of these cells are unknown. Here, we demonstrated that antigen-induced expansion of primary NKTs in vitro associates with the accumulation of a CD62L+ subset and exhaustion of CD62L- cells. Only CD62L+ NKTs survived and proliferated in response to secondary stimulation. When transferred to immune-deficient NSG mice, CD62L+ NKTs persisted 5 times longer than CD62L- NKTs. Moreover, CD62L+ cells transduced with a CD19-specific CAR achieved sustained tumor regression in a B cell lymphoma model. Proliferating CD62L+ cells downregulated or maintained CD62L expression when activated via T cell receptor alone or in combination with costimulatory receptors. We generated HLAnull K562 cell clones that were engineered to express CD1d and costimulatory ligands. Clone B-8-2 (HLAnullCD1dmedCD86high4-1BBLmedOX40Lhigh) induced the highest rates of NKT expansion and CD62L expression. B-8-2-expanded CAR-NKTs exhibited prolonged in vivo persistence and superior therapeutic activities in models of lymphoma and neuroblastoma. Therefore, we have identified CD62L as a marker of a distinct NKT subset endowed with high proliferative potential and have developed artificial antigen-presenting cells that generate CD62L-enriched NKTs for effective cancer immunotherapy.
Pharmacokinetics of oral fumarates in healthy subjects (2004)

The pharmacokinetics of monomethylfumarate in healthy subjects after a single tablet of fumarate are highly variable, particularly after food intake. Further experiments exploring the pharmacokinetics of oral fumarates are warranted in order to elucidate the mechanisms underlying variability in response in patients.
Single Amino Acid Mutations Affect Zika Virus Replication In Vitro and Virulence In Vivo (2020)

The 2014-2016 Zika virus (ZIKV) epidemic in the Americas resulted in large deposits of next-generation sequencing data from clinical samples. This resource was mined to identify emerging mutations and trends in mutations as the outbreak progressed over time. Information on transmission dynamics, prevalence, and persistence of intra-host mutants, and the position of a mutation on a protein were then used to prioritize 544 reported mutations based on their ability to impact ZIKV phenotype. Using this criteria, six mutants (representing naturally occurring mutations) were generated as synthetic infectious clones using a 2015 Puerto Rican epidemic strain PRVABC59 as the parental backbone. The phenotypes of these naturally occurring variants were examined using both cell culture and murine model systems. Mutants had distinct phenotypes, including changes in replication rate, embryo death, and decreased head size. In particular, a NS2B mutant previously detected during in vivo studies in rhesus macaques was found to cause lethal infections in adult mice, abortions in pregnant females, and increased viral genome copies in both brain tissue and blood of female mice. Additionally, mutants with changes in the region of NS3 that interfaces with NS5 during replication displayed reduced replication in the blood of adult mice. This analytical pathway, integrating both bioinformatic and wet lab experiments, provides a foundation for understanding how naturally occurring single mutations affect disease outcome and can be used to predict the of severity of future ZIKV outbreaks. To determine if naturally occurring individual mutations in the Zika virus epidemic genotype affect viral virulence or replication rate in vitro or in vivo, we generated an infectious clone representing the epidemic genotype of stain Puerto Rico, 2015. Using this clone, six mutants were created by changing nucleotides in the genome to cause one to two amino acid substitutions in the encoded proteins. The six mutants we generated represent mutations that differentiated the early epidemic genotype from genotypes that were either ancestral or that occurred later in the epidemic. We assayed each mutant for changes in growth rate, and for virulence in adult mice and pregnant mice. Three of the mutants caused catastrophic embryo effects including increased embryonic death or significant decrease in head diameter. Three other mutants that had mutations in a genome region associated with replication resulted in changes in in vitro and in vivo replication rates. These results illustrate the potential impact of individual mutations in viral phenotype.
Polycyclic aromatic hydrocarbon oxidation by the white-rot fungusBjerkandera sp. strain BOS55 in the presence of nonionic surfactants (1998)

The effect of nonionic surfactants on the polycyclic aromatic hydrocarbon (PAH) oxidation rates by the extracellular ligninolytic enzyme system of the white-rot fungus Bjerkandera sp. strain BOS55 was investigated. Various surfactants increased the rate of anthracene, pyrene, and benzo[a]pyrene oxidation by two to fivefold. The stimulating effect of surfactants was found to be solely due to the increased bioavailability of PAH, indicating that the oxidation of PAH by the extracellular ligninolytic enzymes is limited by low compound bioavailability. The surfactants were shown to improve PAH dissolution rates by increasing their aqueous solubility and by decreasing the PAH precipitate particle size. The surfactant Tween 80 was mineralized by Bjerkandera sp. strain BOS55; as a result both the PAH solubilizing activity of Tween 80 and its stimulatory effect on anthracene and pyrene oxidation rates were lost within 24 h after addition to 6-day-old cultures. It was observed that the surfactant dispersed anthracene precipitates recrystallized into larger particles after Tween 80 was metabolized. However, benzo[a]pyrene precipitates remained dispersed, accounting for a prolonged enhancement of the benzo[a]pyrene oxidation rates. Because the endogenous production of H2O2 is also known to be rate limiting for PAH oxidation, the combined effect of adding surfactants and glucose oxidase was studied. The combined treatment resulted in anthracene and benzo[a]pyrene oxidation rates as high as 1450 and 450 mg L-1 d-1, respectively, by the extracellular fluid of 6-day-old fungal cultures.
Albumin binding of insulins acylated with fatty acids: characterization of the ligand-protein interaction and correlation between binding affinity and timing of the insulin effect in vivo (1995)

Albumin is a multifunctional transport protein that binds a wide variety of endogenous substances and drugs. Insulins with affinity for albumin were engineered by acylation of the epsilon-amino group of LysB29 with saturated fatty acids containing 10-16 carbon atoms. The association constants for binding of the fatty acid acylated insulins to human albumin are in the order of 10(4)-10(5) M-1. The binding apparently involves both non-polar and ionic interactions with the protein. The acylated insulins bind at the long-chain fatty acid binding sites, but the binding affinity is lower than that of the free fatty acids and depends to a relatively small degree on the number of carbon atoms in the fatty acid chain. Differences in affinity of the acylated insulins for albumin are reflected in the relative timing of the blood-glucose-lowering effect after subcutaneous injection into rabbits. The acylated insulins provide a breakthrough in the search for soluble, prolonged-action insulin preparations for basal delivery of the hormone to the diabetic patient. We conclude that the biochemical concept of albumin binding can be applied to protract the effect of insulin, and suggest that derivatization with albumin-binding ligands could be generally applicable to prolong the action profile of peptide drugs.
The Pharmacology of Chinese Herbs (1998)

Introduction A Brief History of Chinese Medicine The Cardiovascular System Herbs with Multiple Actions Cardiac Herbs Antiarrhythmic Herbs Antihypertensive Herbs Antianginal Herbs Antihypercholesteroliemic Herbs Antishock Herbs The Nervous System Anesthetics and Muscle-Relaxing Herbs Sedatives and Hypnotic Herbs Anticonvulsive Herbs Anti-Alzheimer and Nootropic Herbs Analgesic Herbs Antipyretic Herbs Antirheumatic Herbs Central Stimulating Herbs The Alimentary System Stomachic and Wind-Dispelling Herbs Herbs Promoting Digestion Antacid and Antiulcer Herbs Laxative Herbs Antidiarrheal Herbs Emetic and Antiemetic Herbs Choleretic and Antihepatitis Herbs Tonics and Supporting Herbs The Respiratory System Antitussives Expectorants Antiasthmatic Herbs The Genitourinary System Diuretic Herbs Herbs Affecting the Uterus Fertility and Contraceptive Herbs The Hematopoietic System Herbs Promoting Blood Formation Immunoenhancing and Immunosuppressing Herbs Hemostatic and Antistasic Herbs The Endocrine System Herbs Affecting the Thyroid Gland Herbs Affecting the Adrenal Cortex Antidiabetic Herbs Chemotherapy Antibacterial, Antiviral, and Antifungus Herbs Anti-Human Immunodeficiency Viral (HIV) Herbs Antitubercular Herbs Antiseptics and Disinfectants Anthelmintics Antiamebial and Antitrichomonial Herbs Antimalarial Herbs Anticancer Herbs Appendix Index
Islet-Derived CD4 T Cells Targeting Proinsulin in Human Autoimmune Diabetes (2016)

Type 1 diabetes results from chronic autoimmune destruction of insulin-producing β-cells within pancreatic islets. Although insulin is a critical self-antigen in animal models of autoimmune diabetes, due to extremely limited access to pancreas samples, little is known about human antigenic targets for islet-infiltrating T cells. Here we show that proinsulin peptides are targeted by islet-infiltrating T cells from patients with type 1 diabetes. We identified hundreds of T cells from inflamed pancreatic islets of three young organ donors with type 1 diabetes with a short disease duration with high-risk HLA genes using a direct T-cell receptor (TCR) sequencing approach without long-term cell culture. Among 85 selected CD4 TCRs tested for reactivity to preproinsulin peptides presented by diabetes-susceptible HLA-DQ and HLA-DR molecules, one T cell recognized C-peptide amino acids 19–35, and two clones from separate donors responded to insulin B-chain amino acids 9–23 (B:9–23), which are known to be a critical self-antigen–driving disease progress in animal models of autoimmune diabetes. These B:9–23–specific T cells from islets responded to whole proinsulin and islets, whereas previously identified B:9–23 responsive clones from peripheral blood did not, highlighting the importance of proinsulin-specific T cells in the islet microenvironment.
Patterns of survival in patients with recurrent follicular lymphoma: a 20-year study from a single center. (1995)

Age and previous and continuing responsiveness of follicular lymphoma to therapy are the principal determinants of survival following recurrence. Improvement in survival with new treatments will be demonstrated most readily in older patients, while more intensive approaches should be tested in younger patients in whom remission is achieved with difficulty.
Mediation of the Immunomodulatory Effect of β-Estradiol on Inflammatory Responses by Inhibition of Recruitment and Activation of Inflammatory Cells and Their Gene Expression of TNF-α and IFN-γ (2000)

Collectively, the results suggest that E2-mediated inhibition of inflammatory responses may be due to a combination of suppression of homing and activation of inflammatory cells and their production of TNF-alpha and IFN-gamma.
Hormone withdrawal symptoms in oral contraceptive users (2000)

Almost all symptoms assessed were significantly worse during the 7-day hormone-free interval than during the 21 days of hormone-containing pills.
Plaque inhibition assay for drug susceptibility testing of influenza viruses (1980)

The relative antiviral activities of four drugs against contemporary strains of influenza A and B viruses were determined in Madin-Darby canine kidney cell monolayers with a plaque inhibition assay. This assay proved to be a reliable, rapid method of determining 50% inhibitory concentrations that correlated well with clinically achievable drug levels and the results of clinical trials. Contemporary strains of influenza A viruses (subtypes H1N1, H3N2, HSW1N1) required amantadine hydrochloride and rimantadine hydrochloride 50% inhibitory concentrations in the range of 0.2 to 0.4 microgram/ml, whereas 50% inhibitory concentrations ranged from approximately 50 to 100 micrograms/ml against influenza B viruses. Ribavirin was approximately 10-fold less active than amantadine hydrochloride against influenza A viruses, and the ribavirin 50% inhibitory concentrations against both influenza A and B viruses ranged from 2.6 to 6.8 micrograms/ml. Inosiplex had no antiviral activity in this test system.
Optical scanning extrinsic Fabry–Perot interferometer for absolute microdisplacement measurement (1997)

We report an optical-scanning, dual-fiber, extrinsic Fabry-Perot interferometer system for absolute measurement of microdisplacement. The system involves two air-gapped Fabry-Perot cavities, formed by fiber end faces, functioning as sensing and reference elements. Taking the scanning wavelength as an interconverter to compare the gap length of the sensing head with the reference-cavity length yields the absolute measurement of the sensing-cavity length. The measurement is independent of the wavelength-scanning accuracy, and the reference-cavity length can be self-calibrated simply by one's changing the sensing-head length by an accurate value.
Single molecule force spectrometer with magnetic force control and inductive detection (1999)

Mechanical investigations with single molecules have opened a rich spectrum of new experiments, ranging from molecular recognition over polymer elasticity and DNA unzipping to protein unfolding. Here we present the design of a novel instrument, where the force is applied to the molecule via magnetic fields acting on a magnetic cantilever for atomic force microscopy. The performance of this instrument was demonstrated by measuring the binding force of biotin/avidin complexes. A new and technically very appealing detection scheme for measurements of unbinding forces was introduced, which consists of picking up the induced voltage pulse caused by a discontinuous change of the magnet position upon bond rupture.
Angiogenesis and inflammation in invasive carcinoma of the breast. (1997)

The correlations between inflammation and vascularity were weak in this study (r2 about 0.04) and thus there was no evidence of an important relation. Discrepancies between this and other studies may be resolved by studying expression of angiogenic cytokines and proteolytic enzymes by tumour infiltrating inflammatory cells, and their relation to tumour vascularity.
The cytochrome P450 1A2 active site: Topology and perturbations caused by glutamic acid-318 and threonine-319 mutations (1993)

Phenyldiazene reacts with rat liver CYP1A2 expressed in Saccharomyces cerevisiae to give a phenyl-iron complex that rearranges to a mixture (NB:NA:NC:ND = 12:54:14:20, subscript indicates pyrrole ring) of N-phenyl-PPIX (PPIX = protoporphyrin) regioisomers. The same isomer pattern is obtained in each instance when the purified or microsomal enzyme reacts with phenyldiazene, indicating that the active site topology is not altered by removal of the protein from the membrane. Reaction of the enzyme with biphenylhydrazine gives a similar distribution of N-biphenyl-PPIX isomers, but reaction with (2-naphthyl)-hydrazine only gives the NC and ND regioisomers and a trace of the NA isomer of N-(2-naphthyl)-PPIX. The mutations E318D, E318A, and E318V cause relatively minor changes in the observed regioisomer ratios. In contrast, the mutations T319A, T319V, and T319S suppress formation of the NC and ND isomers of N-phenyl-PPIX. The reaction of T319A with biphenylhydrazine yields major amounts of the NB adduct rather than the small amounts observed with CYP1A2 and the Glu-318 mutants, but does not give the NC and ND regioisomers. Other, less dramatic, changes in the isomer ratios are also observed. The results indicate that the active site of CYP1A2 is open above all four quadrants of the heme group including, to some extent, the region above pyrrole ring B. Pyrrole ring B is completely inaccessible in most cytochrome P450 enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacokinetics and Toxicity of Inhaled Human Interferon-α in Patients with Lung Cancer (1989)

Eight patients with advanced, previously treated non-small cell lung cancer inhaled natural leukocyte interferon-alpha (IFN-alpha) from a dosimeter-equipped jet nebulizer. Single doses of IFN ranged from 1 x 10(6) to 120 x 10(6) IU. Serum IFN was undetectable after single doses of 1 x 10(6) to 18 x 10(6) IU, but 60 x 10(6) IU resulted in measurable levels of circulating IFN in 3 out of 6 patients. All 5 patients who inhaled 120 x 10(6) IU had between 11 and 35 IU of IFN per milliliter of serum for at least 12 h. No systemic or local side effects were observed after 1 x 10(6) to 18 x 10(6) IU, but doses of 60 x 10(6) to 120 x 10(6) IU resulted in temperature rise, headache, and malaise. All symptoms started within 3-6 h, reached their peak by 8-10 h, and lasted until 12-24 h after inhalation. A decrease (greater than 20%) in peak expiratory flow following inhalation was temporarily found in 2 patients. We conclude that IFN, given by inhalation, penetrates into the blood stream, thus causing systemic side effects similar to those described after systemic IFN administration and, in addition, occasionally reversible airflow obstruction.
Pumpkin seed inhibitor of human factor XIIa (activated Hageman factor) and bovine trypsin (1982)

A strong inhibitor of human Hageman factor fragment (HFf, beta-factor XIIa) and bovine trypsin was isolated from pumpkin (Cucurbita maxima) seed extracts by acetone fractionation, by chromatography on columns of diethyl-aminoethylcellulose and carboxylmethyl-Sephadex C-25, and by Sephadex G-50 gel filtration. Pumpkin seed Hageman factor inhibitor (PHFI) is unusual in its lack of inhibition of several other serine proteinases tested--human plasma, human urinary, and porcine pancreatic kallikreins, human alpha-thrombin, and bovine alpha-chymotrypsin. Human plasmin and bovine factor Xa are only weakly inhibited. PHFI also inhibits the HFf-dependent activation of plasma prekallikrein and clotting of plasma. Other properties of PHFI are a pI of 8.3, 29 amino acid residues, amino-terminal arginine, carboxyl-terminal glycine, 3 cystine residues, undetectable sulfhydryl groups and carbohydrate, and arginine at the reactive site. The minimum molecular weight of PHFI is 3268 by amino acid analysis. PHFI may be the smallest protein inhibitor of trypsin known.
Endothelial expression of VCAM-1 in experimental crescentic nephritis and effect of antibodies to very late antigen-4 or VCAM-1 on glomerular injury. (1999)

The migration of leukocytes into glomeruli in crescentic glomerulonephritis is fundamental to pathogenesis, and offers important therapeutic opportunities. We addressed the importance of VCAM-1, and its leukocyte ligand very late antigen-4 (VLA-4), in such leukocyte migration. In a rat model of nephrotoxic nephritis, glomerular expression of VCAM-1, studied by immunohistochemistry, was up-regulated by day 6 of nephritis. To quantify kidney endothelial VCAM-1 expression, a differential radiolabeled mAb technique was used, which demonstrated that protein expression was not up-regulated by day 2 of nephritis, but rose threefold between days 2 and 5, and remained elevated until at least day 28. An in vivo study was then performed, using blocking mAbs to either VCAM-1 or VLA-4, starting mAb treatment on the day prior to disease induction, and continuing until animals were sacrificed at day 7. mAbs to VLA-4 significantly attenuated renal injury (albuminuria, glomerular fibrinoid necrosis, and crescent formation), but mAbs to VCAM-1 had no significant effect. Surprisingly, the number of leukocytes within glomeruli was unaffected by anti-VLA-4 mAb therapy, despite the reduction in renal injury. Paradoxically, classical markers of macrophage activation were increased in the anti-VLA-4- and anti-VCAM-1-treated animals. This study demonstrates that kidney endothelial VCAM-1, in contrast to ICAM-1, is not up-regulated by day 2 of nephrotoxic nephritis, and plays little part in early leukocyte influx into glomeruli. However, VLA-4 is an important mediator of glomerular injury, operating after transendothelial leukocyte migration, and presumably binding to alternate ligands within the kidney.
A 39-year-old man with acute hemolytic crisis secondary to intravenous injection of hydrogen peroxide. (1991)

The diagnosis of cancer or its recurrence is often emotionally devastating for patients and those close to them. People may have a great deal of difficulty accepting the diagnosis and may seek others' opinions about the best course of treatment. When a physician projects that there is no hope, or if a cure is no longer probable, the patient and those close to him or her may feel helpless and hopeless. Given the resultant psychologic turmoil, the patient may be led to try unproven methods. Such methods, often referred to as "cancer quackery," represent a person's attempt to reassert personal control in response to these feelings of helplessness and hopelessness. Cancer quackery involves about $2 billion each year in the United States alone. One study demonstrated that approximately 39% of the pediatric outpatients studied had either tried, considered, or received recommendations for unproven methods of cancer treatment. Laetrile and faith healing were the most frequent methods used. One of the most recent of the unproven methods of cancer treatment that have been shown to cause life-threatening complications is IV injection of hydrogen peroxide. The scientific rationale behind this procedure is still unclear, but the side effects are clearly life threatening.