gebhart/patrepeval huggingface dataset:
The Economics and Ethics of Markets for Human Organs (1989)

In 1984, federal legislation outlawing payment for human organs for transplantation was adopted after only cursory discussion of the underlying policy issues. More considered analysis suggests that this prohibition may be overly broad. It appears possible to design suitably regulated market-type approaches to the acquisition and allocation of cadaveric organs (and perhaps of organs from living donors as well) that will be neither unduly offensive to ethical sensibilities nor easily abused and that may yield significant improvements over the existing system of organ procurement, which presents important ethical and practical problems of its own. Moreover, whatever ultimate judgment we reach concerning the merits of markets for transplantable organs, analysis of the sources of the initial moral resistance to the commercialization that lies behind measures such as the 1984 legislation offers insights into the respective roles of market and nonmarket institutions in general.
ChemInform Abstract: STEROIDS. PART 33. RITTER REACTION ON STEROIDS. 3. RING EXPANSION OF STEROID OXETANES INTO DIHYDROOXAZINES (1985)

Abstract Das Epoxymethylen‐androsten (I) reagiert mit den Nitrilen (II) unter Ringerweiterung zu den kondensierten Dihydrooxazinen (III), die als Tetrafluoroborate isoliert werden.
Layer-by-Layer Films from Hyaluronan and Amine-Modified Hyaluronan (2007)

Hyaluronan is a polysaccharide that is increasingly investigated for its role in cellular adhesion and for the preparation of biomimetic matrices for tissue engineering. Hyaluronan gels are prepared for application as space fillers, whereas hyaluronan films are usually obtained by adsorbing or grafting a single hyaluronan layer onto a biomaterial surface. Here, we examine the possibility to employ the layer-by-layer technique to deposit thin films of cationic-modified hyaluronan (HA+) and hyaluronan (HA) of controlled thicknesses. The buildup conditions are investigated, and growth is compared to that of other polyelectrolyte multilayer films containing either HA as the polyanion or HA+ as the polycation. The films could be formed in a low ionic strength medium but are required to be cross-linked prior to contact with a physiological medium. NIH3T3 fibroblasts were perfectly viable on self-assembled hyaluronan films with, however, a preference for hyaluronan ending films. These findings point out the possibility to tune the thickness of thin hyaluronan films at the nanometer scale. Such architectures could be employed for investigating cell/substrate interactions or for functionalizing biomaterial surfaces.
Botulinum Toxin Type A as a Migraine Preventive Treatment (2000)

Pericranial injection of botulinum toxin type A, 25 U, was found to be a safe treatment that significantly reduced migraine frequency, migraine severity, acute medication usage, and associated vomiting.
Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (Trail) Contributes to Interferon γ–Dependent Natural Killer Cell Protection from Tumor Metastasis (2001)

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is expressed by in vitro activated natural killer (NK) cells, but the relevance of this observation to the biological function of NK cells has been unclear. Herein, we have demonstrated the in vivo induction of mouse TRAIL expression on various tissue NK cells and correlated NK cell activation with TRAIL-mediated antimetastatic function in vivo. Expression of TRAIL was only constitutive on a subset of liver NK cells, and innate NK cell control of Renca carcinoma hepatic metastases in the liver was partially TRAIL dependent. Administration of therapeutic doses of interleukin (IL)-12, a powerful inducer of interferon (IFN)-gamma production by NK cells and NKT cells, upregulated TRAIL expression on liver, spleen, and lung NK cells, and IL-12 suppressed metastases in both liver and lung in a TRAIL-dependent fashion. By contrast, alpha-galactosylceramide (alpha-GalCer), a powerful inducer of NKT cell IFN-gamma and IL-4 secretion, suppressed both liver and lung metastases but only stimulated NK cell TRAIL-mediated function in the liver. TRAIL expression was not detected on NK cells from IFN-gamma-deficient mice and TRAIL-mediated antimetastatic effects of IL-12 and alpha-GalCer were strictly IFN-gamma dependent. These results indicated that TRAIL induction on NK cells plays a critical role in IFN-gamma-mediated antimetastatic effects of IL-12 and alpha-GalCer.
Inhibition of PC12 cell redox activity is a specific,early indicator of the mechanism of beta-amyloid-mediated celldeath. (1994)

An in vitro tissue culture cell model system for investigating the biochemical mechanisms involved in the neurodegenerative actions of beta-amyloid has been established. Using rat pheochromocytoma PC12 cells, it was found that an early, specific response of cells to the beta-amyloid protein or the beta-amyloid fragment 25-35 was a potent inhibition of cellular redox activity, as measured by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) reduction. This inhibitory response was rapid and occurred at nanomolar concentrations of peptide, concentrations at which no equivalent decreases in cell proliferation or cell survival were observed. The inhibition of PC12 cell MTT reduction was initially reversible upon removal of the peptide; if sustained for several days, however, by repeated peptide application, it became associated with a dramatic reduction in cell survival. Inhibition of MTT reduction may, therefore, be an early indicator of the mechanism of beta-amyloid-mediated cell death.
Calf's lung surfactant extract in acute hypoxemic respiratory failure in children (1996)

Objective Open-label trial of the safety and short-term efficacy of calf's lung surfactant in pediatric respiratory failure. Design Multi-institutional, uncontrolled, observational trial. Setting Six pediatric intensive care units of tertiary medical centers. Patients Twenty-nine children with acute hypoxemic respiratory failure, characterized by diffuse, bilateral, pulmonary infiltrates, need for ventilator support, and an oxygenation index of >or=to7. Interventions Up to four doses of intratracheal surfactant (80 mL/m2). Measurements and Main Results Ventilator parameters, arterial blood gases, and derived oxygenation and ventilation indices were recorded before, and at intervals after, surfactant administration. Complications and outcome measures were also noted. There was immediate improvement in oxygenation and moderation of ventilator support associated with surfactant administration in 24 of 29 patients. A modest but statistically insignificant effect was seen with subsequent doses. The only complications occurred in three patients who developed airleaks, two of which were coincident with surfactant administration. The overall mortality rate was 14%, which compares favorably with other published series. Conclusions Administration of calf's lung surfactant appears to be safe and is associated with rapid improvement in oxygenation and moderation of ventilator support in children with acute hypoxemic respiratory failure. These results set the stage for a randomized, controlled study. (Crit Care Med 1996; 24:1316-1322)
ChemInform Abstract: SYNTHESIS OF 11‐PHENYL‐5,6‐DIHYDRO‐11H‐DIBENZ(B,E)AZEPINE DERIVATIVES (1981)

Abstract Die Benzylaniline (I) werden mit Benzaldehyd (II) in Gegenwart von Bortrichlorid zu den Carbinolen (III) umgesetzt ,i die mit Schwefelsäure zu den Azepinen (IV) cyclisiert werden.
Stable Prenucleation Calcium Carbonate Clusters (2008)

Calcium carbonate forms scales, geological deposits, biominerals, and ocean sediments. Huge amounts of carbon dioxide are retained as carbonate ions, and calcium ions represent a major contribution to water hardness. Despite its relevance, little is known about the precipitation mechanism of calcium carbonate, and specified complex crystal structures challenge the classical view on nucleation considering the formation of metastable ion clusters. We demonstrate that dissolved calcium carbonate in fact contains stable prenucleation ion clusters forming even in undersaturated solution. The cluster formation can be characterized by means of equilibrium thermodynamics, applying a multiple-binding model, which allows for structural preformation. Stable clusters are the relevant species in calcium carbonate nucleation. Such mechanisms may also be important for the crystallization of other minerals.
IGF-1R as an anti-cancer target--trials and tribulations (2013)

Type I insulin-like growth factor receptor (IGF-1R) has long been recognized for its role in tumorigenesis and growth, but only recently have the tools for targeting the IGF pathway become available. More than 10 IGF/IGF-1R inhibitors have entered clinical trials, and these belong to three main classes: (1) monoclonal antibodies against IGF-1R, (2) monoclonal antibodies against IGF-1R ligands (IGF-1 and IGF-2), and (3) IGF-1R tyrosine kinase inhibitors. These IGF-1R-targeting agents share common effects on IGF-1R signaling but differ in mechanisms of action, spectrum of target inhibition, and pharmacological features. Clinical activity of IGF-1R inhibitors has been demonstrated with sustained responses in a small number of patients with select tumor types, such as Ewing sarcoma and thymoma. However, many large clinical trials involving patients with adult tumors, including non-small cell lung cancer, breast cancer, and pancreatic cancer, failed to show clinical benefit in the overall patient population. Possible reasons for failure include the complexity of the IGF-1R/insulin receptor system and parallel growth and survival pathways, as well as a lack of patient selection markers. While IGF-1R remains a valid target for selected tumor types, identification of predictive markers and rational combinations will be critical to success in future development.
VEGF, VEGFR-1, VEGFR-2, microvessel density and endothelial cell proliferation in tumours of the ovary (1999)

VEGF is an angiogenic factor with potent endothelial cell (EC) proliferative actions. Our aim was to investigate whether expression of VEGF and its receptors and EC proliferation differ between ovarian tumour types and regions of the vasculature. VEGF, VEGFR-1, VEGFR-2 and EC proliferation were examined immuno-histochemically, and in situ hybridisation (ISH) studies of VEGF mRNA expression were performed and assessed in regions of high (HVD) and average (AVD) vessel density. VEGF immunostaining was significantly stronger in HVD regions of malignant compared with borderline serous tumours. VEGF immunostaining did not differ between tumour types; however, the percentage of VEGFR-1- and VEGFR-2-positive vessels was significantly lower in mucinous tumours. No differences were observed between HVD and AVD regions. VEGF ISH signal was observed in 2/7 borderline mucinous tumours, 8/14 malignant serous tumours and 5/13 benign tumours. The EC proliferation index was significantly lower in the HVD regions of serous relative to benign tumours. A negative correlation between VEGFR-1 immunostaining and microvessel density was observed in benign and serous tumours. However, EC proliferation index and VEGFR-1 positivity were positively correlated in benign tumours. Our results suggest that VEGF may play a role in the control of angiogenesis in serous and benign tumours but it does not appear to contribute to the previously reported higher microvessel density in mucinous tumours or to influence heterogeneity of microvessel density in ovarian tumours.
Cell-surface expression and purification of human CD4 produced in baculovirus-infected insect cells. (1989)

CD4 is an integral membrane glycoprotein that acts as the cellular receptor for human immunodeficiency virus (HIV). A cDNA encoding full-length CD4 was inserted into the genome of Autographa californica nuclear polyhedrosis virus under transcriptional regulation of the viral polyhedrin gene promoter. The recombinant virus was used to infect insect cells, which resulted in the abundant expression of CD4 as evaluated by flow cytometry and immunoblot analysis. Recombinant CD4 expressed on the surface of infected insect cells was immunologically indistinguishable from human CD4 when using 11 different anti-CD4 monoclonal antibodies. The extraction of infected cells by phase-transition separation with Triton X-114 followed by immunoaffinity chromatography yielded a single protein detected by NaDodSO4/PAGE using silver staining. N-terminal sequence analysis of the purified recombinant protein showed that CD4 produced in Sf9 cells is efficiently cleaved from the precursor protein. Immunoblot analysis under nondenaturing conditions showed that the purified protein reacted with the anti-CD4 monoclonal antibody Leu-3a. The potential use of the recombinant membrane-associated CD4 in anti-HIV therapy is discussed.
Betaseron. (1998)

Betaseron, an analogue of human beta-interferon where serine was genetically engineered to substitute for cysteine at position 17, is produced in E. coli. The molecule is a small polypeptide of 165 amino acids with a single disulphide bond, and is non-glycosylated. The site-specific substitution was made to obtain a product that is more stable upon storage. Similar to native IFN-beta, Betaseron is hydrophobic in nature and has been shown to have the same panel of biological activities which includes antiviral activity against a variety of viruses, inhibition of cell growth, activation of natural killer cells, and binding to interferon receptors on the cell surface. Betaseron has been tested in a wide variety of clinical settings since 1983. The pivotal trial for the treatment of relapsing-remitting multiple sclerosis began in 1988. A PLA was filed for this indication in 1992 by Berlex and Chiron, and FDA approval was received in 1993. Betaseron is synthesized in E. coli and deposited as inclusion bodies. The manufacturing process involves solubilization and reduction of the insoluble protein, followed by purification by organic extraction, cystine oxidation and size exclusion chromatographic steps. The purified Betaseron is formulated with human serum albumin to maintain solubility at neutral pH. The complete primary sequence of Betaseron was verified by amino and carboxy-terminal sequence analysis, peptide mapping, amino acid analysis and fragment analysis after chemical cleavages. Overlapping amino acid sequence information confirmed that the amino acid sequence is the same as predicted by the DNA sequence. The amino-terminal methionine of Betaseron is removed after synthesis in E. coli. An intramolecular disulphide bond between Cys 31 and Cys 141 formed during the manufacturing process is routinely confirmed by peptide map analysis. The purity of Betaseron is assessed using a panel of analytical methods including non-reducing and reducing SDS-PAGE and reversed phase HPLC analysis where minor product-related components can be identified. These minor species were characterized with respect to their biological and biochemical properties, and identified using a variety of approaches including construction of additional, beta-interferon analogs. There is significant redundancy in the release testing of Betaseron. The amount of characterization information available on this relatively simple molecule along with the extensive manufacturing experience would suggest that some redundant testing could be eliminated for this well-characterized protein.
Increased leukotriene A4 hydrolase expression in the heart of angiotensin II‐induced hypertensive rat (1999)

Leukotriene A(4) (LTA(4)) hydrolase is essential for the conversion of LTA(4) to LTB(4), an inflammatory lipid mediator. We investigated whether LTA(4) hydrolase was regulated in the heart by angiotensin II (ang II) infusion. Continuous ang II infusion via an osmotic minipump for up to 7 days upregulated mRNA and protein levels of LTA(4) hydrolase ( approximately 3.5-fold of control) in the heart in a pressor-dependent manner. Immunohistochemistry demonstrated intense LTA(4) hydrolase staining in the myofibroblast as well as migrated monocytes/macrophages. These data suggest that the cardiac LTA(4) hydrolase-LTB(4) system plays a positive role in the promotion of cardiac inflammation in hypertension.
NaturallyArisingCD4+RegulatoryT Cells forImmunologicSelf-Tolerance andNegativeControl ofImmuneResponses (2003)

Naturally occurring CD4+ regulatory T cells, the majority of which express CD25, are engaged in dominant control of self-reactive T cells, contributing to the maintenance of immunologic self-tolerance. Their depletion or functional alteration leads to the development of autoimmune disease in otherwise normal animals. The majority, if not all, of such CD25+CD4+ regulatory T cells are produced by the normal thymus as a functionally distinct and mature subpopulation of T cells. Their repertoire of antigen specificities is as broad as that of naive T cells, and they are capable of recognizing both self and nonself antigens, thus enabling them to control various immune responses. In addition to antigen recognition, signals through various accessory molecules and via cytokines control their activation, expansion, and survival, and tune their suppressive activity. Furthermore, the generation of CD25+CD4+ regulatory T cells in the immune system is at least in part developmentally and genetically controlled. Genetic defects that primarily affect their development or function can indeed be a primary cause of autoimmune and other inflammatory disorders in humans. Based on recent advances in our understanding of the cellular and molecular basis of this T cell-mediated immune regulation, this review discusses how naturally arising CD25+CD4+ regulatory T cells contribute to the maintenance of immunologic self-tolerance and negative control of various immune responses, and how they can be exploited to prevent and treat autoimmune disease, allergy, cancer, and chronic infection, or establish donor-specific transplantation tolerance.
Diffuse expression of heparan sulfate proteoglycan and connective tissue growth factor in fibrous septa with many mast cells relate to unresolving hepatic fibrosis of congenital hepatic fibrosis (2005)

Abundant CTGF retained diffusely in HSPG in the fibrous portal tracts/septa may be responsible for non-resolving hepatic fibrosis in CHF, and many mast cells and portal MF not related to HSC may causally relate to such characteristic finding in CHF.
Iron polymaltose-induced FGF23 elevation complicated by hypophosphataemic osteomalacia (2009)

Iron-induced renal phosphate wasting, hypophosphataemia and osteomalacia have previously been reported in a small number of Japanese patients receiving parenteral iron sucrose. We report the case history of a European male who, as a result of regular intravenous iron polymaltose, developed prolonged hypophosphataemia complicated by widespread insufficiency fractures. The pathogenesis of this complication remains unknown however our novel finding of a marked elevation in fibroblast growth factor 23 (FGF23), which normalized after ceasing parenteral iron, suggests an important and previously unreported effect of iron on FGF23 homeostasis.
Static detection of second-order vulnerabilities in web applications (2014)

Web applications evolved in the last decades from sim-ple scripts to multi-functional applications. Such com-plex web applications are prone to different types of se-curity vulnerabilities that lead to data leakage or a com-promise of the underlying web server. So called second-order vulnerabilities occur when an attack payload is first stored by the application on the web server and then later on used in a security-critical operation. In this paper, we introduce the first automated static code analysis approach to detect second-order vulnera-bilities and related multi-step exploits in web applica-tions. By analyzing reads and writes to memory loca-tions of the web server, we are able to identify unsani-tized data flows by connecting input and output points of data in persistent data stores such as databases or ses-sion data. As a result, we identified 159 second-order vulnerabilities in six popular web applications such as the conference management systems HotCRP and Open-Conf. Moreover, the analysis of web applications eval-uated in related work revealed that we are able to detect several critical vulnerabilities previously missed. 1
Amplification of the androgen receptor gene is associated with P53 mutation in hormoneârefractory recurrent prostate cancer (1999)

p53 protein expression of 30 hormone-refractory locally recurrent prostate cancers was compared with their matched untreated primary tumour specimens. In addition, androgen receptor (AR) gene amplification and p53 protein immunostaining were compared. p53 positivity increased during hormonal therapy from 17 per cent of the untreated primary tumours to 40 per cent of the hormone-refractory recurrences (p = 0·078). None of the p53-positive primary tumour specimens lost p53 positivity during hormonal therapy. Hormone-refractory recurrences with AR gene amplification more frequently (p = 0·0342) showed positive p53 immunostaining than tumours without AR gene amplification, 75 and 27 per cent, respectively. In summary, this study has shown that a cell clone with P53 mutation seems to be selected for during endocrine therapy and that positive p53 immunostaining correlates with AR gene amplification. These results suggest that inactivation of P53 may lead to genetic instability in a subset of prostate carcinomas enabling them to achieve properties, such as AR gene amplification, that allow them to grow in low levels of androgens and therefore cause tumour progression. Copyright © 1999 John Wiley & Sons, Ltd.
Living Coupling Reaction in Living Cationic Polymerization. 2. Synthesis and Characterization of Amphiphilic A2B2Star−Block Copolymer:  Poly[bis(isobutylene)-star-bis(methyl vinyl ether)] (1998)

Amphiphilic A2B2 star−block copolymers (A = polyisobutylene (PIB) and B = poly(methyl vinyl ether) (PMeVE)) have been prepared via the living coupling reaction of living PIB, using 2,2-bis[4-(1-tolylethenyl)phenyl]propane (BDTEP) as a living coupling agent, followed by the chain ramification reaction of methyl vinyl ether (MeVE) at the junction of the living coupled PIB. Model reactions for the synthesis of A2B2 star−block copolymers indicated that the fine-tuning of Lewis acidity to the reactivity of MeVE is a crucial step for the structural integrity of the resulting A2B2 star−block copolymers. Side products were negligible using a [Ti(OEt)4]/[TiCl4] ratio of 0.7 and the minimum tuning time (∼5 min). Fractionation of the crude A2B2 star−block copolymer was carried out on a silica gel column, and on the basis of the weights of fractions, the purity of the crude A2B2 star−block copolymer was calculated to be ≥93.5%. Two Tgs (−60 °C for PIB and −20 °C for PMeVE) were observed for the star−block copolymer by DSC indicating the presence of two microphases. An A2B2 star−block copolymer with 80 wt % PMeVE composition ((IB45)2-s-(MeVE170)2) exhibited a critical micelle concentration (cmc) of 4.25 × 10-4 M in water, which is an order of magnitude higher than cmcs obtained with linear diblock copolymers with same total Mn and composition (IB90-b-MeVE340) or with same segmental lengths (IB45-b-MeVE170). This suggests that block copolymers with star architectures exhibit less tendency to micellization than their corresponding linear diblock copolymers. Average particle sizes in aqueous solution above the cmc were measured to be from 41 to 177 nm, depending on the architecture and/or the molecular weight.