gebhart/patrepeval huggingface dataset:
Models, mechanisms and etiology of tumour promotion: proceedings of a symposium organized by the Hungarian Cancer Society and the IARC, held in Budapest, 16-18 May 1983 (1984)

Models, mechanisms and etiology of tumour promotion: proceedings of a symposium organized by the Hungarian Cancer Society and the IARC, held in Budapest, 16-18 May 1983 , Models, mechanisms and etiology of tumour promotion: proceedings of a symposium organized by the Hun... , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
New Preparation Method for Polymer‐Electrolyte Fuel Cells (1995)

A new preparation method for the catalyst layer in the electrodes of a polymer electrolyte fuel cell, based on the process of preparing perfluorosulfonate‐ionomer (PFSI) colloid, was developed. In this method, both a good network of PFSI and uniformity of PFSIs on Pt particles were achieved with colloid formation of PFSI chains in the specific organic solvents. The applicable organic solvents had dielectric constants ranging from 3 to 10. The PFSI colloids were selectively adsorbed onto the carbon agglomerates with highly dispersed Pt particles on the surface, and a catalyst paste‐formation followed. Then the catalyst paste was spread over a carbon paper representing the gas diffusion layer, and two sheets of carbon paper with catalyst paste on them were hot pressed onto an ion‐exchange membrane from both sides. This simple preparation method provided high performance in fuel cells at low temperature (50°C).
New Insight into the Therapeutic Role of 5-HT1A Receptors in Central Nervous System Disorders (2010)

The serotonergic system plays a crucial role in regulating psychoemotional, cognitive and motor functions in the central nervous system (CNS). Among 5-HT receptor subtypes, 5-HT(1A) receptors have long been implicated in the pathogenesis and treatment of anxiety and depressive disorders. 5-HT(1A) receptors function as both presynaptic (autoreceptor) and postsynaptic receptors in specific brain regions such as the limbic areas, septum and raphe nuclei. 5-HT(1A) receptors negatively regulate cAMP-dependent signal transduction and inhibit neuronal activity by opening G-protein-gated inwardly rectifying potassium channels. The therapeutic action of 5-HT(1A) agonists and their mechanism in alleviating anxiety and depressive disorders have been well documented. In addition, recent studies have revealed new insights into the therapeutic role of 5-HT(1A) receptors in treating various CNS disorders, including not only depressive disorders (e.g., delayed onset of action and refractory symptoms), but also schizophrenia (e.g., cognitive impairment and antipsychotic-induced extrapyramidal side effects) and Parkinson's disease (e.g., extrapyramidal motor symptoms and L-DOPA-induced dyskinesia). These lines of evidences encourage us to design new generation 5-HT(1A) ligands such as 5-HT(1A) agonists with greater potency, higher selectivity and improved pharmacokinetic properties, and 5-HT(1A) ligands which combine multiple pharmacological actions (e.g., inhibition of serotonin transporter, dopamine D(2) receptors and other 5-HT receptor subtypes). Such new 5-HT(1A) ligands may overcome clinical efficacy limitations and/or improve adverse reactions in current CNS therapies.
Surface‐active phospholipid: a Pandora’s box of clinical applications. Part II. Barrier and lubricating properties (2002)

In Part I, it was described how their configuration renders phospholipid molecules surface active and capable of acting at interfaces in addition to the liquid-air interface to which conventional theory has hitherto confined the study of 'surfactant' in the lung. Surface-active phospholipid (SAPL) appears no different to comparable surfactants studied in the physical sciences for the highly desirable properties that their adsorption (reversible binding) can impart to solid surfaces. In Part II, these properties are considered in sites where there is no air. Highly desirable properties include boundary lubrication (lubricity), release (antistick) and the ability of the strongly adsorbed and strongly cohesive SAPL linings to act as barriers against abrasion, corrosion and, possibly, against invasion by microorganisms. As the 'sealant', it could be the true barrier rather than the cells providing its mechanical support. Evidence is reviewed for SAPL providing the gastric mucosal barrier to acid in the stomach and preventing the digestion of Helicobacter pylori until that barrier is broken by bile in the duodenum, where H. pylori cause ulcers. The concept that SAPL provides effortless sliding of many tissues, including pleura, pericardium and peritoneum is reviewed. Particular attention is paid to the load-bearing joints, where a deficiency has been associated with osteoarthritis. The ability of the same SAPL lining to perform multiple roles is discussed in relation to the peritoneum, where it could provide the lubricant/release agent preventing surgical adhesions, while imparting semipermeability to 'the membrane' vital for peritoneal dialysis. In each site, the prophylactic use of exogenous SAPL is discussed for its potential clinical applications.
Graft-versus-leukemia following bone marrow transplantation. (1987)

Considerable data in animals suggest an anti-leukemia reaction associated with transplantation of allogeneic bone marrow cells. In some instances, this graft-versus leukemia (GVL) reaction may be distinct from graft-versus-host-disease (GVHD). Data in humans also support the concept of a GVL effect associated with bone marrow transplantation. These observations include an increased risk of leukemia relapse in identical twin transplants and in recipients of T cell-depleted allogeneic transplants, and a decreased risk-of leukemia relapse in individuals who develop acute or chronic GVHD. These findings are among the most convincing evidence that the immune system plays a role against cancer in man.
Chinese Hamster Ovary Cell Mutants Defective in Glycosaminoglycan Assembly and Glucuronosyltransferase I (1999)

The proteoglycans of animal cells typically contain one or more heparan sulfate or chondroitin sulfate chains. These glycosaminoglycans assemble on a tetrasaccharide primer, -GlcAbeta1, 3Galbeta1,3Galbeta1,4Xylbeta-O-, attached to specific serine residues in the core protein. Studies of Chinese hamster ovary cell mutants defective in the first or second enzymes of the pathway (xylosyltransferase and galactosyltransferase I) show that the assembly of the primer occurs by sequential transfer of single monosaccharide residues from the corresponding high energy nucleotide sugar donor to the non-reducing end of the growing chain. In order to study the other reactions involved in linkage tetrasaccharide assembly, we have devised a powerful selection method based on induced resistance to a mitotoxin composed of basic fibroblast growth factor-saporin. One class of mutants does not incorporate 35SO4 and [6-3H]GlcN into glycosaminoglycan chains. Incubation of these cells with naphthol-beta-D-xyloside (Xylbeta-O-Np) resulted in accumulation of linkage region intermediates containing 1 or 2 mol of galactose (Galbeta1, 4Xylbeta-O-Np and Galbeta1, 3Galbeta1, 4Xylbeta-O-Np) and sialic acid (Siaalpha2,3Galbeta1, 3Galbeta1, 4Xylbeta-O-Np) but not any GlcA-containing oligosaccharides. Extracts of the mutants completely lacked UDP-glucuronic acid:Galbeta1,3Gal-R glucuronosyltransferase (GlcAT-I) activity, as measured by the transfer of GlcA from UDP-GlcA to Galbeta1,3Galbeta-O-naphthalenemethanol (<0.2 versus 3.6 pmol/min/mg). The mutation most likely lies in the structural gene encoding GlcAT-I since transfection of the mutant with a cDNA for GlcAT-I completely restored enzyme activity and glycosaminoglycan synthesis. These findings suggest that a single GlcAT effects the biosynthesis of common linkage region of both heparan sulfate and chondroitin sulfate in Chinese hamster ovary cells.
Comparative efficacy of alemtuzumab and&nbsp;established treatment in the management of&nbsp;multiple sclerosis (2015)

Alemtuzumab is the newest disease-modifying therapy approved for the treatment of relapsing multiple sclerosis. Alemtuzumab is an anti-CD52 targeted antibody that causes lysis of T and B lymphocytes, monocytes, natural killer cells, macrophages, and dendritic cells. Following its administration, a prolonged T-cell lymphopenia results with emergence of a reconstituted immune system that differs in its composition from that pretreatment. In clinical trials, alemtuzumab has shown impressive efficacy with regard to clinical and radiological outcomes in relapsing multiple sclerosis, along with sustained long-term beneficial effects, and it is attractive for its once-yearly administration. Despite this, the occurrence of serious secondary autoimmune disorders, infections, and a potential risk of malignancy necessitates a careful evaluation of risks versus benefits for an individual patient prior to its use. The requirement of patient commitment to the intense mandatory monitoring program is also a factor to be considered when incorporating alemtuzumab into the treatment regimen.
Effects of recombinant and hybrid recombinant human leukocyte interferons on cytotoxic activity of natural killer cells. (1983)

Two recombinant human leukocyte interferons (A and D), five hybrid interferons containing varying portions of A and D, and one fibroblast recombinant interferon were tested over a wide range of concentrations for their ability to modulate cytolytic activity of human natural killer (NK) cells. All of the interferons tested were purified to homogeneity. Although all the interferons were active, there were significant quantitative differences in their ability to augment cytolysis and the rank order of potency was reproducible among donors. The various recombinant interferons were also tested for their ability to augment mouse NK activity and the parental D and the A/D hybrids exhibited significant augmentation of cytolysis, which was consistent with their interspecies reactivity in viral neutralization assays. There generally was a direct correlation between antiviral activity and the ability of interferon to augment mouse NK activity; however, this correlation was not evident when tested on human cells. The study of these hybrids led to the identification of two molecules (A/D Bgl and A/D Pvu) which are very active in augmenting mouse NK activity. In addition, considerable insight has been obtained regarding the structure-function relationship of these leukocyte interferons and their ability to boost murine NK. This biological activity was associated with the COOH-terminal portion of the D interferon.
Resistance to an Herbivore Through Engineered Cyanogenic Glucoside Synthesis (2001)

The entire pathway for synthesis of the tyrosine-derived cyanogenic glucoside dhurrin has been transferred from Sorghum bicolor to Arabidopsis thaliana. Here, we document that genetically engineered plants are able to synthesize and store large amounts of new natural products. The presence of dhurrin in the transgenic A. thaliana plants confers resistance to the flea beetle Phyllotreta nemorum, which is a natural pest of other members of the crucifer group, demonstrating the potential utility of cyanogenic glucosides in plant defense.
Near-Field Investigations of the Landers Earthquake Sequence, April to July 1992 (1993)

The Landers earthquake, which had a moment magnitude (M(w)) of 7.3, was the largest earthquake to strike the contiguous United States in 40 years. This earthquake resulted from the rupture of five major and many minor right-lateral faults near the southern end of the eastern California shear zone, just north of the San Andreas fault. Its M(w) 6.1 preshock and M(w) 6.2 aftershock had their own aftershocks and foreshocks. Surficial geological observations are consistent with local and far-field seismologic observations of the earthquake. Large surficial offsets (as great as 6 meters) and a relatively short rupture length (85 kilometers) are consistent with seismological calculations of a high stress drop (200 bars), which is in turn consistent with an apparently long recurrence interval for these faults.
Linker-Mediated Modulation of the Chemiluminescent Signal from N10-(3-Sulfopropyl)-N-sulfonylacridinium-9-carboxamide Tracers (2000)

Four chemiluminescent N-sulfonylacridinium-9-carboxamide active esters (17-20) were prepared from the corresponding acids and coupled to both of the aminated phenobarbital (13) and N-(6-aminohexyl)phenytoin (16) haptens. The level of signal produced by chemiluminescent N-sulfonylacridinium-9-carboxamide phenobarbital and phenytoin tracers in a solid-phase immunoassay format was found to be modulated by at least 20-fold by the judicious choice of the reactive acridinium-hapten linking group.
Characterization of point-plane corona in air at radio frequency using a FE-FCT method (1999)

The development of corona under RF conditions in point-plane configuration has been investigated in this paper, using the recently developed finite-element flux-corrected transport (FE-FCT) method. The study was made in air for a 1 cm gap with 50 µm tip radius needle at 40 MHz and the effects of different parameters, such as the peak applied voltage (in the range 3-4.5 kV) on the coronal development and particularly on the current and light output, are examined. Polarity and hysteresis effects are observed, as well as a plateau in the current waveform, which are confirmed by previously published experimental results. Finally, a Fourier analysis on the steady-state current waveform is performed.
Non-neuronal and neuronal BACE1 elevation in association with angiopathic and leptomeningeal β-amyloid deposition in the human brain (2015)

These results suggest that BACE1 elevation in the endothelia and perivascular neurites may be involved in angiopathic Aβ deposition, while BACE1 elevation in meningeal cells might contribute Aβ to leptomeningeal amyloidosis.
PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells (2004)

Both positive and negative regulatory roles have been suggested for the B7 family member PD-L1(B7-H1). PD-L1 is expressed on antigen-presenting cells (APCs), activated T cells, and a variety of tissues, but the functional significance of PD-L1 on each cell type is not yet clear. To dissect the functions of PD-L1 in vivo , we generated PD-L1-deficient (PD-L1 –/– ) mice. CD4 + and CD8 + T cell responses were markedly enhanced in PD-L1 –/– mice compared with wild-type mice in vitro and in vivo . PD-L1 –/– dendritic cells stimulated greater wild-type CD4 + T cell responses than wild-type dendritic cells, and PD-L1 –/– CD4 + T cells produced more cytokines than wild-type CD4 + T cells in vitro , demonstrating an inhibitory role for PD-L1 on APCs and T cells. In vivo CD8 + T cell responses also were significantly enhanced, indicating that PD-L1 has a role in limiting the expansion or survival of CD8 + T cells. Studies using the myelin oligodendrocyte model of experimental autoimmune encephalomyelitis showed that PD-L1 on T cells and in host tissues limits responses of self-reactive CD4 + T cells in vivo . PD-L1 deficiency converted the 129S4/SvJae strain from a resistant to experimental autoimmune encephalomyelitis-susceptible strain. Transfer of encephalitogenic T cells from wild-type mice into PD-L1 –/– recipients led to exacerbated disease. Disease was even more severe in PD-L1 –/– recipients of PD-L1 –/– T cells. These results demonstrate that PD-L1 on T cells, APCs, and host tissue inhibits naïve and effector T cell responses and plays a critical role in T cell tolerance.
Recent advances in cutaneous melanoma oncogenesis research. (1994)

The oncogenic transformation of epidermal melanocytes produces primary cutaneous melanoma. In this article, previously published cytogenetic, biochemical, molecular biology, and cell biology studies of cutaneous melanoma oncogenesis are reviewed. A variety of laboratory animal models have been developed for studies of the induction of melanoma, including mice, the laboratory opossum Monodelphis domestica, Sinclair swine, and Xiphophorus fish. Some of the advantages and disadvantages of these animal models are presented for comparison to human melanoma. Cytogenetic and loss of heterozygosity studies over the past decade have demonstrated that human metastatic melanomas contain numerous chromosomal abnormalities, and that normal melanocytes have putative tumor suppressor genes that are presumably deleted or inactivated in transformed melanocytes to yield malignant melanoma cells. The status of research efforts to identify the putative tumor suppressor genes of human chromosomes 1p, 6q, and 9p, implicated in sporadic and familial melanoma, is presented. Furthermore, the roles of ultraviolet radiation, genetic susceptibility, dominant oncogenes, growth factors, the p53 gene, antioxidant enzymes, and DNA tumor viruses in the formation of cutaneous primary melanoma are discussed.
Cobalt dependence of the magneto-optical response in magnetoplasmonic nanodisks (2010)

In this work, we study the plasmon-mediated enhancement of the magneto-optical (MO) activity in the case of Au/Co/Au nanodisks as a function of the Co content. We show that both the spectral shape and amplitude of the complex polar Kerr rotation are modified by the relative amount of gold (diamagnetic) and cobalt (ferromagnetic). We demonstrate that such shape modification is dictated by the predominance of the absorptive or dispersive part of the MO constant in each material, which is intimately related to the origin of their MO activity.
A Digital Signature Scheme Secure Against Adaptive Chosen-Message Attacks (1988)

We present a digital signature scheme based on the computational difficulty of integer factorization. The scheme possesses the novel property of being robust against an adaptive chosen-message attack: an adversary who receives signatures for messages of his choice (where each message may be chosen in a way that depends on the signatures of previously chosen messages) cannot later forge the signature of even a single additional message. This may be somewhat surprising, since in the folklore the properties of having forgery being equivalent to factoring and being invulnerable to an adaptive chosen-message attack were considered to be contradictory. More generally, we show how to construct a signature scheme with such properties based on the existence of a “claw-free” pair of permutations—a potentially weaker assumption than the intractibility of integer factorization. The new scheme is potentially practical: signing and verifying signatures are reasonably fast, and signatures are compact.
Phase I study of MK-3475 (anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. (2012)

2512 Background: Programmed death-1 (PD-1) is an inhibitory T-cell coreceptor that may lead to suppression of antitumor immunity. MK-3475 is a humanized monoclonal IgG4 antibody against PD-1. Preclinically, MK-3475 has shown antitumor activity in multiple tumor types. This first-in-human phase I trial explored safety, PK, PD, and antitumor activity of MK-3475. Methods: An open-label, dose escalation study was conducted in patients with advanced malignancy refractory to standard therapy. Cohorts of 3-6 patients were enrolled (3+3 design) at escalating IV doses of 1, 3, and 10 mg/kg. Following an initial dose and 28-day Cycle 1, patients were allowed to subsequently receive multiple doses given every 2 wks. Radiographic assessment was conducted every 8 wks using RECIST 1.1 guidelines. Results: Nine patients, 3 at each dose level, completed the dose-limiting toxicity (DLT) period (28 d). Patients had non–small cell lung cancer (NSCLC, n=3), rectal cancer (n=2), melanoma (MEL, n=2), sarcoma (n=1), or carcinoid (n=1). To date, a total of 63 doses were administered (median 7/patient; max 12) without DLT. Drug-related adverse events (AEs) across all doses included Grade 1 fatigue (n=3), nausea (n=2), diarrhea (n=1), dysgeusia (n=1), breast pain (n=1), and pruritus (n=1). One drug-related Grade 2 AE of pruritus was reported. No drug-related AEs ≥ Grade 3 were observed. PK data are shown in the table. Based on RECIST, 1 patient with MEL on therapy &gt;6 mths had a partial response, and preliminary evidence of tumor size reduction (stable disease) was observed in 3 additional patients with advanced cancer. Conclusions: MK-3475 was well-tolerated without DLT across 3 tested dose levels. Evidence of antitumor activity was observed. Enrollment continues to obtain additional safety, PK, and efficacy data; updated data will be presented at the meeting. [Table: see text]
Activin type IIA and IIB receptors mediate Gdf11 signaling in axial vertebral patterning (2002)

Vertebral bodies are segmented along the anteroposterior (AP) body axis, and the segmental identity of the vertebrae is determined by the unique expression pattern of multiple Hox genes. Recent studies have demonstrated that a transforming growth factor beta (TGF-beta) family protein, Gdf11 (growth and differentiation factor 11), and the activin type II receptor, ActRIIB, are involved in controlling the spatiotemporal expression of multiple Hox genes along the AP axis, and that the disruption of each of these genes causes anterior transformation of the vertebrae. Skeletal defects are more severe in Gdf11-null mice than in ActRIIB-null mice, however, leaving it uncertain whether Gdf11 signals via ActRIIB. Here we demonstrate using genetic and biochemical studies that ActRIIB and its subfamily receptor, ActRIIA, cooperatively mediate the Gdf11 signal in patterning the axial vertebrae, and that Gdf11 binds to both ActRIIA and ActRIIB, and induces phosphorylation of Smad2. In addition, we also show that these two receptors can functionally compensate for one another to mediate signaling of another TGF-beta ligand, nodal, during left-right patterning and the development of anterior head structure.
The DNA Damage Signaling Pathway Connects Oncogenic Stress to Cellular Senescence (2007)

The mechanisms of tumor suppression must be linked to the oncogenic threats that may affect a normal cell. An important cancer causing mechanism is the accidental activation of genes that stimulate cell proliferation (oncogenes) by a variety of endogenous or environmental mutagens. This event has been experimentally modelled by enforcing the expression of oncogenes in primary cells. The astonishing outcome of these manipulations is that oncogenes trigger antiproliferative responses preventing progression to malignant transformation. These responses bring to an end proliferation due to cell death or a permanent cell cycle arrest called senescence. Here we review evidence indicating that oncogene induced senescence (OIS) involves activation of p53 via the DNA damage response (DDR). These results imply mechanisms of DNA damage in cells expressing oncogenes, that may be secondary to reactive oxygen species and/or some form of "oncogenic stress" that affect normal DNA replication. Interestingly, DNA damage signals persist in cells that escape from senescence. The implications of these signals for tumorigenesis are also discussed. Given that DNA damage signals have now been observed in cells treated with any stimuli known to induce senescence, the process can be redefined as a metabolically viable but permanent cell cycle arrest with persistent DNA damage signaling.