gebhart/patrepeval huggingface dataset:
Hormonal therapy in cancer of the breast. V. The effect of methyltestosterone on clinical course and hormonal excretion (1953)

T earned a well-deserved place in the armaineiitariuin of physicians treating advanced mammary canter.Unfortunately, these agents have the disadvantage of requiring parenteral administration.Methyltestosterone is an androgen which is clinically effective both by oral and buccal administration.However, its effect on hormonal excretion,'; carbohydrate metabolism: production of gynecornastia,s and hepatic functionl is known to differ from that of parenterally administered testosterone or its esters.We recently published comparative studies on androstenedio1,s a weak androgen, and its 17-methyl analogue.'Whereas neither of these agents appeared to be so effective as testosterone or its esters, there did not appear to be any great change in anticancer activity produced by the 17-methyl substituent.Indeed, 17-methylandrostenediol was slightly more effective than the parent androstenediol.Because of these considerations, it was decided to undertake the administration of niethyltestosteione to a series of patients with advanced cancer of the breast. MATERIAL AND METHODSThis compound is a 17-a-methyl-A-'-androstene-3-one, 17p 01, according to the nomenclature proposed by Fieser and Fieser.It has a melting point of 163" to 164" C .and was designated as Compound No. 244 by Selye.
Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction (2002)

Enoxaparin is associated with similar TIMI 3 flow rates as UFH at an early time point while exhibiting advantages over UFH with respect to ischemic events through 30 days. These findings with enoxaparin are achieved with a similar risk of major hemorrhage.
Mass Spectrometry Based Targeted Protein Quantification: Methods and Applications (2008)

The recent advance in technology for mass spectrometry-based targeted protein quantification has opened new avenues for a broad range of proteomic applications in clinical research. The major breakthroughs are highlighted by the capability of using a "universal" approach to perform quantitative assays for a wide spectrum of proteins with minimum restrictions and the ease of assembling multiplex detections in a single measurement. The quantitative approach relies on the use of synthetic stable isotope labeled peptides or proteins, which precisely mimic their endogenous counterparts and act as internal standards to quantify the corresponding candidate proteins. This report reviews recently developed platform technologies for emerging applications of clinical proteomics and biomarker development.
Platelet/Polymorphonuclear Leukocyte Interaction: P-Selectin Triggers Protein-Tyrosine Phosphorylation–Dependent CD11b/CD18 Adhesion: Role of PSGL-1 as a Signaling Molecule (1999)

Abstract Polymorphonuclear leukocyte (PMN) adhesion to activated platelets is important for the recruitment of PMN at sites of vascular damage and thrombus formation. We have recently shown that binding of activated platelets to PMN in mixed cell suspensions under shear involves P-selectin and the activated β2-integrin CD11b/CD18. Integrin activation required signaling mechanisms that were sensitive to tyrosine kinase inhibitors.1 Here we show that mixing activated, paraformaldehyde (PFA)-fixed platelets with PMNs under shear conditions leads to rapid and fully reversible tyrosine phosphorylation of a prominent protein of 110 kD (P∼110). Phosphorylation was both Ca2+ and Mg2+ dependent and was blocked by antibodies against P-selectin or CD11b/CD18, suggesting that both adhesion molecules need to engage with their respective ligands to trigger phosphorylation of P∼110. The inhibition of P∼110 phosphorylation by tyrosine kinase inhibitors correlates with the inhibition of platelet/PMN aggregation. Similar effects were observed when platelets were substituted by P-selectin–transfected Chinese hamster ovary (CHO-P) cells or when PMN were stimulated with P-selectin–IgG fusion protein. CHO-P/PMN mixed-cell aggregation and P-selectin–IgG–triggered PMN/PMN aggregation as well as P∼110 phosphorylation were all blocked by antibodies against P-selectin or CD18. In each case PMN adhesion was sensitive to the tyrosine kinase inhibitor genistein. The antibody PL-1 against P-selectin glycoprotein ligand-1 (PSGL-1) blocked platelet/PMN aggregation, indicating that PSGL-1 was the major tethering ligand for P-selectin in this experimental system. Moreover, engagement of PSGL-1 with a nonadhesion blocking antibody triggered β2-integrin–dependent genistein-sensitive aggregation as well as tyrosine phosphorylation in PMN. This study shows that binding of P-selectin to PSGL-1 triggers tyrosine kinase–dependent mechanisms that lead to CD11b/CD18 activation in PMN. The availability of the β2-integrin to engage with its ligands on the neighboring cells is necessary for the tyrosine phosphorylation of P∼110.
5G NR PDCCH: Design and Performance (2018)

This paper analyzes physical downlink control channel (PDCCH) for 5G New Radio (NR) technology defined as part of Rel-15 3GPP physical layer specifications. The particular combination of design elements makes NR PDCCH unique compared to the PDCCH or EPDCCH designs in LTE. We focus on the physical aspects of NR PDCCH structure and provide an in-depth summary of the design considerations, analysis of novel search space (SS) design options to better balance the PDCCH blind decoding (BD) and channel estimation capabilities, and performance evaluation of various transmission schemes and configurations supported by NR PDCCH. This study attests the flexibility and robustness of NR PDCCH design in addition to potential further enhancements for the scenarios with more stringent reliability requirements, e.g., URLLC applications.
Handbook on Injectable Drugs. (1977)

Handbook on injectable drugs , Handbook on injectable drugs , کتابخانه مرکزی دانشگاه علوم پزشکی تهران
Rehabilitation Robot with Patient-Cooperative Control for Bimanual Training of Hemiparetic Subjects (2011)

Hemiparesis is the most common motor deficit following stroke. Bimanual training and robot-assisted therapy are often used to regain motor functionality of the paretic limb. The goal of this study is the development and validation of a bimanual training system that stimulates the use of both arms of hemiparetic subjects. The adaptive assistance control adjusts the contribution of the unaffected arm, thus reducing the load on the paretic arm. Hemiparetic subjects performed three different tracking exercises in bimanual mode and in two unimanual modes to validate the applicability of the system. In bimanual mode, the patient uses the unaffected limb to initiate and guide the movement. The movement of the paretic limb must be coordinated with the unaffected limb to complete the exercise. The training resulted in improvements of motor performance. High and significant correlation between bimanual training and unimanual performance was observed.
Contribution of Active Site Residues to Substrate Hydrolysis by USP2: Insights into Catalysis by Ubiquitin Specific Proteases (2011)

The ubiquitin-specific protease (USP) structural class represents the largest and most diverse family of deubiquitinating enzymes (DUBs). Many USPs assume important biological roles and emerge as potential targets for therapeutic intervention. A clear understanding of USP catalytic mechanism requires a functional evaluation of the proposed key active site residues. Crystallographic data of ubiquitin aldehyde adducts of USP catalytic cores provided structural details on the catalytic triad residues, namely the conserved Cys and His, and a variable putative third residue, and inferred indirect structural roles for two other conserved residues (Asn and Asp), in stabilizing via a bridging water molecule the oxyanion of the tetrahedral intermediate (TI). We have expressed the catalytic domain of USP2 and probed by site-directed mutagenesis the role of these active site residues in the hydrolysis of peptide and isopeptide substrates, including a synthetic K48-linked diubiquitin substrate for which a label-free, mass spectrometry based assay has been developed to monitor cleavage. Hydrolysis of ubiquitin-AMC, a model substrate, was not affected by the mutations. Molecular dynamics simulations of USP2, free and complexed with the TI of a bona fide isopeptide substrate, were carried out. We found that Asn271 is structurally poised to directly stabilize the oxyanion developed in the acylation step, while being structurally supported by the adjacent absolutely conserved Asp575. Mutagenesis data functionally confirmed this structural role independent of the nature (isopeptide vs peptide) of the bond being cleaved. We also found that Asn574, structurally located as the third member of the catalytic triad, does not fulfill this role functionally. A dual supporting role is inferred from double-point mutation and structural data for the absolutely conserved residue Asp575, in oxyanion hole formation, and in maintaining the correct alignment and protonation of His557 for catalytic competency.
A new routing protocol for the reconfigurable wireless networks (2002)

We propose a new routing protocol, the Zone Routing Protocol (ZRP), for the reconfigurable wireless networks, a large scale, highly mobile ad-hoc networking environment. The novelty of the ZRP protocol is that it is applicable to large flat-routed networks. Furthermore, through the use of the zone radius parameter, the scheme exhibits the adjustable hybrid behavior of proactive and reactive routing schemes. We evaluate the performance of the protocol, showing the reduction in the number of control messages, as compared with other reactive schemes, such as flooding.
A new evolutionary scenario for the Mycobacterium tuberculosis complex (2002)

The distribution of 20 variable regions resulting from insertion-deletion events in the genomes of the tubercle bacilli has been evaluated in a total of 100 strains of Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium canettii, Mycobacterium microti, and Mycobacterium bovis. This approach showed that the majority of these polymorphisms did not occur independently in the different strains of the M. tuberculosis complex but, rather, resulted from ancient, irreversible genetic events in common progenitor strains. Based on the presence or absence of an M. tuberculosis specific deletion (TbD1), M. tuberculosis strains can be divided into ancestral and "modern" strains, the latter comprising representatives of major epidemics like the Beijing, Haarlem, and African M. tuberculosis clusters. Furthermore, successive loss of DNA, reflected by region of difference 9 and other subsequent deletions, was identified for an evolutionary lineage represented by M. africanum, M. microti, and M. bovis that diverged from the progenitor of the present M. tuberculosis strains before TbD1 occurred. These findings contradict the often-presented hypothesis that M. tuberculosis, the etiological agent of human tuberculosis evolved from M. bovis, the agent of bovine disease. M. canettii and ancestral M. tuberculosis strains lack none of these deleted regions, and, therefore, seem to be direct descendants of tubercle bacilli that existed before the M. africanum-->M. bovis lineage separated from the M. tuberculosis lineage. This observation suggests that the common ancestor of the tubercle bacilli resembled M. tuberculosis or M. canettii and could well have been a human pathogen already.
Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects (1996)

We tested peptide immunotherapy in cat-allergic humans, using a formation of two synthetic peptides, IPC-1 and IPC-2, each of which is 27 amino acids long and contains T cell-reactive regions of Fel d 1, the major cat allergen. In this exploratory, randomized, double-blind, parallel-group study, 42 subjects received s.c. injections of treatment peptides 250 micrograms or placebo weekly for four consecutive weeks. Changes in immediate- and late-phase skin test reactivity, and in antigen-driven cytokine synthesis were assessed. Epicutaneous (end-point titration) and intradermal tests were performed with cat extract (ALK SQ Cat Hair) containing Fel d 1, before the first injection, then 2, 6 and 24 weeks after the fourth and last injection of peptides or placebo. IL-4, IL-10 and IFN-gamma expression by circulating peripheral blood mononuclear cells (PBMC) in response to cat extract was measured using short-term bulk culture of PBMC and short-term limiting dilution analysis. Subjects who received peptide immunotherapy did not tolerate significantly more cat extract containing Fel d 1 in the skin tests 2, 6 or 24 weeks after the last injection than they did at baseline, and their late-phase responses did not decrease significantly compared to baseline. Substantial IL-4, IL-10 and IFN-gamma responses were observed following primary culture of cat antigen-stimulated PBMC; however, the intensity of cytokine synthesis and the IFN-gamma: IL-4 ratio were unchanged in peptide- and placebo-treated groups 6 and 24 weeks after the last injection. A few hours after the injections, subjects receiving peptides reported more allergic rhinitis and asthma symptoms and more pruritus than those receiving placebo. We conclude that under the conditions tested, peptide immunotherapy did not reduce immediate- or late-phase skin reactivity to cat extract containing Fel d 1 or modify cat antigen-specific cytokine production significantly.
Efficient Induction of Hepatocyte Spheroids in a Suspension Culture Using a Water-Soluble Synthetic Polymer as an Artificial Matrix (1998)

The preparation of hepatocyte spheroids by adding a water-soluble synthetic polymer as an artificial matrix was performed in a cell suspension system. Cell-aggregation was promoted without cytotoxicity by adding Eudragit (a copolymer of methacrylic acid and methylmethacrylate) to the culture medium. Spheroid-like cell aggregates, whose liver functions were enhanced, were effectively formed in the presence of 0.1% Eudragit, independent of the cultural substratum. Moreover, the mass preparation of spheroids could be achieved with a high production yield by means of a suspension culture in a spinner flask. In this case, the polymer protected the cells from damage due to agitation. The spheroids induced with Eudragit expressed high liver functions, such as albumin secretion, ammonia removal, and urea synthesis. On histological observation, the spheroids showed a well-developed cell adhesion apparatus and bile canaliculi. In addition, a higher calcium ion concentration in the cells of spheroids was observed compared with in monolayer cells.
100-mW high-power angled-stripe superluminescent diodes with a new real refractive-index-guided self-aligned structure (1996)

We have developed 100-mW high-power angled-stripe superluminescent diodes with a new angled-stripe real refractive-index guided self-aligned structure. The structure has a GaAlAs optical confinement layer on a planar active layer and an inclined current injection stripe by 5/spl deg/ with respect to the facet normal. The structure gives small internal loss (/spl sim/10 cm/sup -1/) and facet power reflectivity less than the order of 10/sup -6/. As a result, the output power as high as 105 mW at a low operating current of 270 mA is obtained with less than 3% spectral modulation and 10.5 nm full width at half maximum (FWHM) spectral width.
Horizontal transmission and retention of malignancy, as well as functional human genes, after spontaneous fusion of human glioblastoma and hamster host cells in vivo (2011)

Cell fusion in vitro has been used to study cancer, gene mapping and regulation, and the production of antibodies via hybridomas. However, in-vivo heterosynkaryon formation by cell-cell fusion has received less attention. This investigation describes the spontaneous fusion of a human glioblastoma with normal hamster cells after xenogeneic transplantation, resulting in malignant cells that express both human and hamster genes and gene products, and retention of glioblastoma traits with an enhanced ability to metastasize. Three of 7 human genes found showed translation of their proteins during serial propagation in vivo or in vitro for years; namely, CD74, CXCR4 and PLAGL2, each implicated with malignancy or glioblastoma. This supports the thesis that genetic hybridization of cancer and normal cells can transmit malignancy and also, as first described herein, regulatory genes involved in the tumor's organotypic morphology. Evidence also is increasing that even cell-free human cancer DNA can induce malignancy and transfer genetic information to normal cells. Hence, we posit that the transfer of genetic information between tumor and stromal cells, whether by cell-cell fusion or other mechanisms, is implicated in the progression of malignancy, and may further define the crosstalk between cancer cells and their stromal neighbors.
Roles of membrane‐type matrix metalloproteinase‐1 in tumor invasion and metastasis (2005)

Degradation of extracellular matrix (ECM) is one of the first steps in tumor invasion and metastasis. Matrix metalloproteinases (MMP) have been strongly implicated in this step. Membrane-type MMP-1 (MT1-MMP) was first identified as an activator of proMMP-2 expressed on the surface of tumor cells and later, not only ECM macromolecules but also various biologically important molecules, were shown to serve as substrates for MT1-MMP. Accumulated lines of evidence have demonstrated that MT1-MMP expression level is closely associated with invasiveness and malignancy of tumors, suggesting that MT1-MMP is one of the most critical factors for tumor invasion and metastasis. Despite enthusiasm for MMP inhibitors, phase III trials have not yet demonstrated significance in overall survival and side-effects remain an issue. An understanding of the functions of MT1-MMP could supply clues for developing novel therapeutic strategies targeting MT1-MMP.
Targeting cognitive deficits in schizophrenia: a review of the development of a new class of medicines from the perspective of community mental health researchers (2011)

The evolving concept of neurocognition and the current guidelines for the design and methodology of clinical trials of cognitive-enhancing drugs for the treatment of individuals with schizophrenia are critically examined. The future directions in the development of cognitive-enhancing medicines for the treatment of schizophrenia from the perspective of clinicians and researchers from community mental health settings are discussed.
Growth Factor Synthesis and Human Breast Cancer Progression (1995)

Data obtained using long-established human breast cancer cell lines have suggested that autocrine growth factors secreted by the cells are important for their growth in vitro. Such data alone cannot definitively establish a role for autocrine growth factors in human breast cancer cell proliferation in vivo, but they create a paradigm that can be tested by analysis of data obtained with primary breast cancer cells and tissues. This review is aimed at examining experimental data obtained using fresh human breast cancer cells and tissues to determine whether the results obtained are consistent with predictions made by autocrine models of human breast cancer cell proliferation. Conceptually, for autocrine loops to be of primary importance in human breast cancer cell proliferation, breast cancer cells in vivo must 1) synthesize biologically active growth factors that are available to growth factor receptors, 2) synthesize the cognate growth factor receptors, 3) require the specific factors for proliferation, and 4) express the autocrine loop as a pathologic, rather than a physiologic, process. Since the proportion of tumors that express growth factors of a given family is consistently higher than the proportion of tumors that express the cognate receptors, it is likely that growth factor synthesis has an important, nonautocrine role in breast cancer progression as well. Data obtained with primary human breast cancer specimens indicate that growth factors synthesized by breast cancer cells have an important role in tumor development and progression but that these factors act in a true autocrine fashion only in a subset of tumors.
Cardiovascular disease and hyperlipidaemia (1994)

Life Sciences Division, Department of Molecular and Nuclear Medicine, Lawrence Berkeley Laboratory, University of California, Berkeley, California, USA *Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
Intracellular trafficking of influenza virus: clinical implications for molecular medicine (2001)

The trafficking and processing steps that occur in cells that are infected with influenza virus play a crucial role in the outcome of infection. These steps are targets for new and future anti-viral drugs, and can affect the relative virulence of the virus and its ability to cause disease. The virus first binds to its host cell via specific sialic acid residues, which can control the species tropism of the virus. The internalisation of the virus, into the nucleus of the cell, is dependent on a low pH, and this process is therapeutically targeted by the drug amantadine. Following replication, the newly formed viral genomes leave the nucleus and assemble into infectious particles at the plasma membrane. The targeting and processing of the various viral components at this late stage of the infectious cycle can have a major effect on the ability of the virus to spread and cause disease in its host. Finally, the release of viruses is dependent on the enzyme neuraminidase (NA), and this function has recently been targeted by the NA inhibitors, a new generation of drugs against influenza virus.
Durability and correlates of vaccine protection against Zika virus in rhesus monkeys (2017)

An effective Zika virus (ZIKV) vaccine will require long-term durable protection. Several ZIKV vaccine candidates have demonstrated protective efficacy in nonhuman primates, but these studies have typically involved ZIKV challenge shortly after vaccination at peak immunity. We show that a single immunization with an adenovirus vector-based vaccine, as well as two immunizations with a purified inactivated virus vaccine, afforded robust protection against ZIKV challenge in rhesus monkeys at 1 year after vaccination. In contrast, two immunizations with an optimized DNA vaccine, which provided complete protection at peak immunity, resulted in reduced protective efficacy at 1 year that was associated with declining neutralizing antibody titers to subprotective levels. These data define a microneutralization log titer of 2.0 to 2.1 as the threshold required for durable protection against ZIKV challenge in this model. Moreover, our findings demonstrate that protection against ZIKV challenge in rhesus monkeys is possible for at least 1 year with a single-shot vaccine.
An adaptive congestion control scheme for real-time packet video transport (1993)

In this paper we show that modulating the source rate of a video encoder based on feedback information from the network results in graceful degradation in picture quality during periods of congestion. Such source rate modulation techniques have been used in the past in designing video encoders used to generate data at a fixed rate. In such constant bit rate encoders, the source rate modulation is done using feedback information about the occupancy of a local buffer. Since the buffer is local, the feedback information is available instantaneously to the encoder. In the proposed scheme, the feedback information is delayed because it comes from within a packet-switching network. The feedback provides information about the traffic at switches along the path of the video connection. We show that the proposed scheme performs well, even though the information is delayed for relatively large intervals of time. We believe that the use of such schemes will simplify the architecture used for supporting real-time services in future nationwide gigabit networks.