gebhart/patrepeval huggingface dataset:
Atrial natriuretic peptide in a rat model of cardiac failure. Atrial and ventricular mRNA, atrial content, plasma levels, and effect of volume loading. (1989)

This study examined the relation between synthesis, atrial storage, and plasma levels of atrial natriuretic peptide (ANP), and it examined plasma ANP levels and hemodynamic output in response to volume expansion in a rat model of myocardial infarction and failure. Arterial ANP concentrations did not correlate linearly with infarct size, but they did show an abrupt increase when infarct size exceeded 30% of the left ventricle, similar to the abrupt increase of left ventricular end-diastolic pressure with infarct size greater than 30%. Consequently, a close relation was found between plasma ANP levels and left ventricular end-diastolic pressure (n = 23, r = 0.89, p less than 0.001). Atrial ANP content per gram of tissue but not ANP content per pair of atria was reduced in rats with large infarcts (greater than 40%, p less than 0.05 vs. control animals). ANP mRNA level per pair of atria (related to total atrial RNA), determined by liquid hybridization (controlled by northern blot analysis), was increased by 38% in infarcted rats (p less than 0.05 vs. controls), but the ratio of atrial ANP mRNA relative to atrial beta-actin mRNA levels was not increased. Right and left ventricular ANP mRNA level increased by 90% and 380%, respectively, far exceeding the concomitant increase in beta-actin mRNA (+26% in the left ventricle). Plasma ANP increased with volume loading in controls and rats with moderate infarcts but not in rats with large infarcts despite a similar increase in right atrial pressure (compared with control animals); thus, the relation of delta ANP/delta right atrial pressure exerted by volume loading decreased in rats with large infarcts. Similarly, the response of cardiac output and renal blood flow (determined by radioactive microspheres) to volume loading was attenuated in rats with large infarcts. Thus, in this model of chronic cardiac failure, the activation of the ANP system is closely coupled with the increase in intracardiac pressures without correlating linearly to the extent of myocardial loss. Second, in severe cardiac failure, additional stimulation such as volume loading may elicit only an attenuated ANP secretion response, for example, due to saturation of the ANP receptor sensing system or to a limited transformation rate of pro-ANP. Third, the increase in atrial ANP synthesis and the increase in atrial ANP gene expression seems limited; however, substantial specific ANP gene expression occurs in the ventricles, which, in turn, may contribute to increased plasma ANP levels in chronic heart failure.
Prostate cancer disparities in Black men of African descent: a comparative literature review of prostate cancer burden among Black men in the United States, Caribbean, United Kingdom, and West Africa (2009)

The growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry follows the path of the Transatlantic Slave Trade. To better understand and address the global prostate cancer disparities seen in Black men of West African ancestry, future studies should explore the genetic and environmental risk factors for prostate cancer among this group.
Recovering Internet Service Sessions from Operating System Failures (2005)

Current Internet service architectures lack support for salvaging stateful client sessions when the underlying operating system fails due to hangs, crashes, deadlocks, or panics. The backdoors (BD) system is designed to detect such failures and recover service sessions in clusters of Internet servers by extracting lightweight state associated with client service sessions from server memory. The BD architecture combines hardware and software mechanisms to enable accurate monitoring and remote healing actions, even in the presence of failures that render a system unavailable.
A controlled study of Tourette syndrome. I. Attention-deficit disorder, learning disorders, and school problems. (1987)

Tourette syndrome (TS) is a common, hereditary, neurobehavioral disorder of childhood. To determine the frequency of various behavioral manifestations, we have compared 47 random normal controls to 246 patients with TS, 17 with attention-deficit disorder (ADD), and 15 with ADD secondary to a TS gene (ADD 2(0) TS). All subjects were examined prospectively with a 425-item questionnaire based on the Diagnostic Interview Schedule and the Diagnostic and Statistical Manual of Mental Disorders (DSM III). The TS patients were divided into grade 1 (too mild to treat [17.5%]), grade 2 (requiring treatment [58.9%]), and grade 3 (severe [23.6%]). Patients in all three grades of TS were significantly different from controls for DSM III symptoms of inattention, impulsivity, and hyperactivity. Sixty-two percent of TS patients had ADD, compared with 6.3% of controls; and 48.8% had ADD with hyperactivity (ADDH), compared with 4.2% of controls. In the majority of TS patients, the natural history of the disease was to start with ADDH and 2.4 years later develop motor and vocal tics. Among TS patients, 39% had previously received medication for ADDH or behavior problems, compared with 2% of the controls. Although stimulants can occasionally exacerbate tics, there was no evidence that stimulants cause TS and they are often a valuable adjunct to the treatment of TS. It is estimated that 10%-30% of ADDH is due to or associated with the presence of a TS gene. TS patients had a significantly increased frequency of (1) attending classes for the educationally handicapped, (2) placement in classes for the severely emotionally disturbed, (3) attending any special classes, (4) severe test anxiety, (5) stuttering, (6) letter, number, or word reversal, (7) reading very slowly, and (8) poor retention of material read. A reading-problem score (dyslexia) greater than or equal to 3 was present in 26.8% of TS patients, compared with 4.2% of controls. Number reversal, word reversal, and poor retention were significant even for the TS patients with tics too mild to treat. The multiple ways in which TS impacts school performance, as well as potential remedies, are discussed.
RSVP-TE: Extensions to RSVP for LSP Tunnels (2001)

This document describes the use of RSVP (Resource Reservation Protocol), including all the necessary extensions, to establish label-switched paths (LSPs) in MPLS (Multi-Protocol Label Switching).Since the flow along an LSP is completely identified by the label applied at the ingress node of the path, these paths may be treated as tunnels.A key application of LSP tunnels is traffic engineering with MPLS as specified in RFC 2702.We propose several additional objects that extend RSVP, allowing the establishment of explicitly routed label switched paths using RSVP as a signaling protocol.The result is the instantiation of labelswitched tunnels which can be automatically routed away from network failures, congestion, and bottlenecks.
Possible Incompatibility between Amino Acids and Copper in Solutions for Pediatric Parenteral Nutrition (2014)

The nutrient formulas used for parenteral nutrition are highly complex admixtures of multiple solutions, infused by the IV route to patients who are unable to receive nutrition by mouth or by the enteral route. The administered products contain macronutrients (amino acids, dextrose, and lipids), electrolytes (sodium, potassium, calcium, phosphate, magnesium, chloride, and acetate), micronutrients (vitamins, trace elements), and water. The solution for parenteral administration can be prepared as a “2-in-1” solution, with lipids being infused separately from the other components, or as a “3-in-1” admixture, in which all components are mixed together. 1 The complexity of these solutions poses a significant risk of incompatibility between components. The most widely known incompatibility involving components of parenteral nutrition solutions is precipitation of calcium phosphate. In 1994, the US Food and Drug Administration published a safe ty communication describing cases of incompatibility between calcium and phosphate in parenteral nutrition solutions, in which infusion of the solutions resulted in death (2 patients) or respiratory distress (2 patients). 2 Measures taken to prevent adverse events related to incompatibilities include the use of filters during infusion, specifically 0.22-µm filters for 2-in-1 solutions and 1.2-µm filters for 3-in-1 admixtures. For compounded parenteral nutrition solutions, components should be added in the same order every time, and contact between incompatible solutions should be minimized. 3 Specif ically, phosphates should be added at the beginning of the mixing sequence, and calcium gluconate should be added last, such that the calcium is added when the volume of the solution being compounded is at its maximum. 1
Cerebrospinal fluid A?42 is increased early in sporadic Alzheimer's disease and declines with disease progression (1999)

All mutations known to cause familial Alzheimer's disease (AD) act by increasing the levels of soluble beta-amyloid peptide (A beta), especially the longer form, A beta42. However, in vivo elevation of soluble A beta in sporadic AD has so far not been shown. In the present study, we used enzyme-linked immunosorbent assays specific for A beta42 and A beta40 to investigate cerebrospinal fluid from sporadic AD at different stages of disease severity, to clarify the roles of A beta42 and A beta40 during disease progression. We also evaluated three other groups--one group of patients with mild cognitive impairment who were at risk of developing dementia, a cognitively intact, nondemented reference group diagnosed with depression, and a perfectly healthy control group. We found that A beta42 is strongly elevated in early and mid stages of AD, and thereafter it declines with disease progression. On the contrary, A beta40 levels were decreased in early and mid stages of AD. The group of cognitively impaired patients and the depression reference group had significantly higher levels of A beta42 than the healthy control group, implying that A beta42 is increased not only in AD, but in other central nervous system conditions as well. Our data also point out the importance of having thoroughly examined control material. The initial increase and subsequent decrease of A beta42 adds a new biochemical tool to follow the progression of AD and might be important in the monitoring of therapeutics.
Analysis of basic fibroblast growth factor in rats with inherited retinal degeneration (1996)

In RCS rats, photoreceptors degenerate between postnatal days 20 and 60, secondary to a genetic defect expressed in the neonatal retinal pigmented epithelium (RPE). Previous work has shown delay of the photoreceptor degeneration in this model by intraocular injection of basic fibroblast growth factor (bFGF). Evidence is presented here, from bFGF immunostaining and Northern analysis of bFGF mRNA, for reduced bFGF expression in uncultured RPE of dystrophic RCS pups. It is also shown that in the mutant eyes angiogenesis in the underlying choroid, which normally occurs between postnatal days 7 and 10, is markedly delayed, with irregular distribution of vessels, consistent with a reduction in this known angiogenesis factor. Mutational analysis of the bFGF transcript and gene by denaturing gradient gel electrophoresis and Southern analysis did not, however, reveal abnormalities in the coding sequence of this gene in RCS rats.
Wnt‐5a and G‐protein signaling are required for collagen‐induced DDR1 receptor activation and normal mammary cell adhesion (2002)

The collagen-induced phosphorylation of discoidin domain receptor 1 (DDR1) in Wnt-5a-expressing HB2 mammary cells was effectively inhibited by pertussis toxin, but not by cholera toxin or antibodies blocking beta(1) integrins. Moreover, pertussis toxin reduced adhesion of the cells to collagen by approximately 50%, and antibodies against beta(1) integrins had a similar effect that was in fact additive to that of pertussis toxin. Cholera toxin had accordingly no such effect on adhesion. By comparison, pertussis toxin did not influence adhesion of Wnt-5a-antisense HB2 cells or MCF-7 mammary tumor cells, neither of which express Wnt-5a or exhibit activation of DDR1. In accordance with these results, direct mastoparan-induced activation of G-proteins in Wnt-5a-deficient MCF-7 cells enabled collagen-induced phosphorylation of DDR1 and enhanced their adhesion. The inactive analogue mastoparan-17 had no such effects on MCF-7 cells nor did active mastoparan affect adhesion of Wnt-5a-expressing HB2 cells. A possible explanation for how DDR1, a receptor tyrosine kinase (RTK), potentiates mammary cell adhesion comes from our observations that pertussis toxin also inhibited the recruitment of the cytoskeletal regulator phosphatidylinositol 3-kinase (PI3K) to DDR1 as well as its phosphorylation/activation. In accordance with that, the PI3K inhibitor wortmannin significantly impaired adhesion of normal Wnt-5a-expressing HB2 cells but had little effect on adhesion of Wnt-5a-antisense HB2 cells. Thus, a G(i/o)-protein signaling pathway mediates the effect of Wnt-5a expression by enabling collagen-induced activation of DDR1, which, in parallel with beta(1) integrins, regulates adhesion of mammary cells.
Low Reserve of Cytochrome c Oxidase Capacity in Vivo in the Respiratory Chain of a Variety of Human Cell Types (1998)

The question of whether and to what extent the in vivo cytochrome c oxidase (COX) capacity in mammalian cells exceeds that required to support respiration is still unresolved. In the present work, to address this question, a newly developed approach for measuring the rate of COX activity, either as an isolated step or as a respiratory chain-integrated step, has been applied to a variety of human cell types, including several tumor-derived semidifferentiated cell lines, as well as specialized cells removed from the organism. KCN titration assays, carried out on intact uncoupled cells, have clearly shown that the COX capacity is in low excess (16-40%) with respect to that required to support the endogenous respiration rate. Furthermore, measurements of O2 consumption rate supported by 0.4 mM tetramethyl-p-phenylenediamine in antimycin-inhibited uncoupled intact cells have given results that are fully consistent with those obtained in the KCN titration experiments. Similarly, KCN titration assays on digitonin-permeabilized cells have revealed a COX capacity that is nearly limiting (7-22% excess) for ADP + glutamate/malate-dependent respiration. The present observations, therefore, substantiate the conclusion that the in vivo control of respiration by COX is much tighter than has been generally assumed on the basis of experiments carried out on isolated mitochondria. This conclusion has important implications for understanding the role of physiological or pathological factors in affecting the COX threshold.
Engineering Functional Antithrombin Exosites in α1-Proteinase Inhibitor That Specifically Promote the Inhibition of Factor Xa and Factor IXa (2008)

We have previously shown that residues Tyr-253 and Glu-255 in the serpin antithrombin function as exosites to promote the inhibition of factor Xa and factor IXa when the serpin is conformationally activated by heparin. Here we show that functional exosites can be engineered at homologous positions in a P1 Arg variant of the serpin alpha1-proteinase inhibitor (alpha1PI) that does not require heparin for activation. The combined effect of the two exosites increased the association rate constant for the reactions of alpha1PI with factors Xa and IXa 11-14-fold, comparable with their rate-enhancing effects on the reactions of heparin-activated antithrombin with these proteases. The effects of the engineered exosites were specific, alpha1PI inhibitor reactions with trypsin and thrombin being unaffected. Mutation of Arg-150 in factor Xa, which interacts with the exosite residues in heparin-activated antithrombin, abrogated the ability of the engineered exosites in alpha1PI to promote factor Xa inhibition. Binding studies showed that the exosites enhance the Michaelis complex interaction of alpha1PI with S195A factor Xa as they do with the heparin-activated antithrombin interaction. Replacement of the P4-P2 AIP reactive loop residues in the alpha1PI exosite variant with a preferred IEG substrate sequence for factor Xa modestly enhanced the reactivity of the exosite mutant inhibitor with factor Xa by approximately 2-fold but greatly increased the selectivity of alpha1PI for inhibiting factor Xa over thrombin by approximately 1000-fold. Together, these results show that a specific and selective inhibitor of factor Xa can be engineered by incorporating factor Xa exosite and reactive site recognition determinants in a serpin.
New agents for endocrine resistance in breast cancer (2017)

Estrogen receptor positive (ER+) and HER2-negative (HER2-) breast cancer (BC) is the most common BC subtype, defined by expression of the ER and absence of HER2 amplification. Endocrine treatment (ET), aiming at therapeutic blockade of ER signaling, represents the therapeutic mainstay for patients with both early and advanced disease. Despite its wide therapeutic efficacy, ET fails for a proportion of ER+, HER2- BC patients with early disease who develop endocrine resistance, resulting in disease recurrence. Endocrine resistance occurs almost invariably in patients with metastatic disease. Recently, increasing understanding of the molecular mediators of endocrine resistance has been achieved. This review focuses on the molecular mechanisms mediating endocrine resistance, on molecularly targeted agents to overcome or delay it, and potential predictive biomarkers for accurate patient stratification.
Two simple and rugged designs for creating microfluidic sheath flow (2008)

A simple design capable of 2-dimensional hydrodynamic focusing is proposed and successfully demonstrated. In the past, most microfluidic sheath flow systems have often only confined the sample solution on the sides, leaving the top and bottom of the sample stream in contact with the floor and ceiling of the channel. While relatively simple to build, these designs increase the risk of adsorption of sample components to the top and bottom of the channel. A few designs have been successful in completely sheathing the sample stream, but these typically require multiple sheath inputs and several alignment steps. In the designs presented here, full sheathing is accomplished using as few as one sheath input, which eliminates the need to carefully balance the flow of two or more sheath inlets. The design is easily manufactured using current microfabrication techniques. Furthermore, the sample and sheath fluid can be subsequently separated for recapture of the sample fluid or re-use of the sheath fluid. Designs were demonstrated in poly(dimethylsiloxane) (PDMS) using soft lithography and poly(methyl methacrylate) (PMMA) using micromilling and laser ablation.
Mechanisms of p53 loss in human sarcomas. (1990)

An important role for the p53 gene in neoplastic transformation in vitro and in vivo has been imputed by functional studies and identification of tumor-acquired gene defects or alterations in its expression. To study the generality and mechanisms of p53 alteration in human cancer, we examined 241 tumors of several types for structural aberrations of the locus. Alterations of the gene or its RNA or protein products consistent with loss of function by either recessive or dominant mechanisms were identified among this set uniquely in rhabdomyosarcomas and osteosarcomas. The alterations of p53 in rhabdomyosarcoma tumors included cases with complete deletion of both p53 alleles, complete deletions of one allele with or without point mutation of the remaining allele, and absence of detectable RNA. Similarly, we detected homozygous deletion and lack of expression of p53 RNA or aberrant expression of p53 protein in osteosarcomas. These observations provide strong support for the inclusion of the p53 locus in the group of loci whose functional inactivation by either dominant or recessive modes plays a significant role in human cancer.
Pharmacokinetics and Concentration-Effect Relationship of Oral LSD in Humans (2015)

These first data on the pharmacokinetics and concentration-effect relationship of oral lysergic acid diethylamide are relevant for further clinical studies and serve as a reference for the assessment of intoxication with lysergic acid diethylamide.
Seven Yearsʼ Experience with Antilymphoblast Globulin for Renal Transplantation From Cadaver Donors (1976)

Antibody of the IgGab type can be isolated from horses immunized with cultured human lymphoblasts plus complete Freund's adjuvant. The essential steps for the production of a safe, potent anti-human lymphoblast globulin (ALG) are: A) the use of early bleedings after immunization to reduce the titer of antibodies which react with red blood cells and platelets; B) careful absorption with human red blood cell stroma and platelets; C) stabilization with non-crystalline silica dioxide; D) chromatography through QAE sephadex to remove pyrogens, microaggregates and possible inhibitors of ALG activity; E) careful safety testing in animals for toxicity and pyrogenicity; and F) testing in vitro for sterility. Such a purified horse ALG (IgGab) can be administered safely intravenously to patients to supplement a standardized immunosuppressive regimen incorporating azathioprine and prednisone. Under these circumstances, allergic reactions are very rare, antibodies to horse IgG do not develop, skin tests to horse IgG remain negative, and immune elimination of circulating horse IgG from the human circulation cannot be demonstrated. The overall results of ALG patient survival and transplant function after 184 consecutive first cadaver transplants at the University of Minnesota demonstrate a statistically significant improvement in both parameters accompanying increases in ALG dose while rigidly utilizing standardized doses of azathioprine and prednisone. There is a significant reduction in the number of grafts lost to rejection; significant reduction in the number of rejection episodes; significant delay in the onset of rejection episodes; but there is no increase in septic loss of patients or kidneys. These efforts could be seen in the gross data or when subgroups controlling for patient age, tissue typing were analyzed. Excluding patients at high risk did not alter the results. The beneficial effects of ALG were particularly striking in good matches. In the highest doses, ALG may be dangerous for older patients with poor matches who develop an increased incidence of septic loss of kidney and/or life. Thus, ALG appears to be a useful adjunct in the early management of cadaver transplants by reducing the incidence and frequency of rejection episodes. The dose should probably be reduced in the older patients who receive kidneys from badly mismatched donors. One cannot conclude from this study that ALG manufactured in other centers by this or other techniques, will accomplish the same results since the multiplicity of factors involved in the success and failure of transplants must be controlled so that the influence of intravening variables in the assessment of ALG effectiveness can be assessed.