gebhart/patrepeval huggingface dataset:
Functional Consequences of APO-1/Fas (CD95) Antigen Expression by Normal and Neoplastic Hematopoietic Cells (1995)

Murine monoclonal antibody (mAb) 7C11 binds to the same cell surface epitope as anti-APO-1 and anti-Fas and reacts specifically with cells transfected with a cDNA encoding the human Fas antigen. Furthermore, incubation with 7C11 causes death of hematopoietic cell lines that express APO-1/Fas but not APO-1/Fas-negative cell lines. 7C11 therefore recognizes the human APO-1/Fas (CD95) antigen, a 40 to 50 kDa cell surface glycoprotein that can trigger apoptosis or programmed cell death. Expression of APO-1/Fas antigen by normal and neoplastic hematopoietic cells was determined by flow cytometry using 7C11. APO-1/Fas is expressed by approximately 30 to 40% of resting peripheral blood T cells, B cells, and monocytes and by approximately 5% of resting NK cells and thymocytes. It was not detected on granulocytes, erythrocytes, or platelets. Approximately 80 to 90% of activated T cells, B cells, and thymocytes express APO-1/Fas, as do the majority of activated NK cells. Perturbation of APO-1/Fas by 7C11 does not affect the viability of resting lymphocytes or monocytes. In contrast, activated T cells and NK cells undergo apoptosis within 3 hours of exposure to 7C11. Other mAb that stimulate T cells or NK cells do not cause rapid induction of programmed cell death. APO-1/Fas antigen is expressed by many cell lines of lymphoid and myeloid lineage. However, this antigen was detected on neoplastic cells from only one of 69 patients with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, or multiple myeloma. Only 3 out of 25 tumor samples from patients with non-Hodgkin's lymphoma were found to express APO-1/Fas. All three of these lymphomas harbored the bcl-2-Ig fusion gene associated with the chromosomal translocation t (14;18). Conversely, only 27% of lymphomas that possessed the bcl-2-Ig gene were found to express the APO-1/Fas antigen. Like normal activated lymphocytes, leukemia and lymphoma cells that expressed APO-1/Fas antigen were found to undergo apoptosis in vitro after incubation with 7C11. The APO-1/Fas antigen appears to regulate the growth of normal hematopoietic cells, and the marked upregulation of this antigen on activated normal lymphocytes contrasts sharply with the absence of APO-1/Fas on neoplastic cells of hematopoietic lineage. Defects in the apoptotic signal delivered through this antigen might contribute to the pathogenesis of hematopoietic neoplasms. Thus, the gene encoding APO-1/Fas can be considered a novel type of tumor suppressor gene, just as bcl-2 can be considered a cellular proto-oncogene.
Oxidative stress and left ventricular remodelling after myocardial infarction (2008)

In acute myocardial infarction (MI), reactive oxygen species (ROS) are generated in the ischaemic myocardium especially after reperfusion. ROS directly injure the cell membrane and cause cell death. However, ROS also stimulate signal transduction to elaborate inflammatory cytokines, e.g. tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and -6, in the ischaemic region and surrounding myocardium as a host reaction. Inflammatory cytokines also regulate cell survival and cell death in the chain reaction with ROS. Both ROS and inflammatory cytokines are cardiodepressant mainly due to impairment of intracellular Ca(2+) homeostasis. Inflammatory cytokines stimulate apoptosis through a TNF-alpha receptor/caspase pathway, whereas Ca(2+) overload induced by extensive ROS generation causes necrosis through enhanced permeability of the mitochondrial membrane (mitochondrial permeability transition). Apoptosis signal-regulating kinase-1 (ASK1) is an ROS-sensitive, mitogen-activated protein kinase kinase kinase that is activated by many stress signals and can activate nuclear factor kappaB and other transcription factors. ASK1-deficient mice demonstrate that the ROS/ASK1 pathway is involved in necrotic as well as apoptotic cell death, indicating that ASK1 may be a therapeutic target to reduce left ventricular (LV) remodelling after MI. ROS and inflammatory cytokines activate matrix metalloproteinases which degrade extracellular matrix, causing a slippage of myofibrils and hence LV dilatation. Consequently, collagen deposition is increased and tissue repair is enhanced with myocardial fibrosis and angiogenesis. Since the extent of LV remodelling is a major predictor of prognosis of the patients with MI, the therapeutic approach to attenuating LV remodelling is critically important.
ChemInform Abstract: New Pharmaceutical Excipients in Solid Dosage Forms (2012)

Abstract Review: 26 refs.
Detection of Hydrogen Peroxide with Fluorescent Dyes (2017)

Constant improvements will lead to the generation of probes that are not only more sensitive but also specifically tailored to individual cellular compartments. Antioxid. Redox Signal. 29, 585-602.
Stimulation of anti-influenza cytolytic T lymphocytes by a synthetic peptide of the influenza hemagglutinin can be modulated by at least three independent helper factors. (1984)

Secondary murine anti-influenza cytolytic T lymphocytes (CTL) could be induced in vitro by the chemically synthesized peptide HA1(181-204), corresponding to amino acids 181-204 of the hemagglutinin molecule of influenza strain A/Japan/305/57. This stimulation required the addition of exogenous helper factors, termed CHFP, which could be obtained from supernatant fluids of the WEHI-3 cell line or spleen cells stimulated by either concanavalin A or Sendai virus. Because the activities from these three sources could reflect different molecules, they were referred to as CHFPW, CHFPC, and CHFPS, respectively. When CHFPS was fractionated by using reverse-phase high performance liquid chromatography (HPLC), the CHFP activity was found to elute at two hydrophobicities. The more hydrophilic factor(s) was designated CHFPS1, while the more hydrophobic factor(s) was called CHFPS2. Similarly, CHFPW could be separated into more hydrophilic (CHFPW1) and more hydrophobic (CHFPW2) molecules. In contrast, CHFPC molecules eluted at only one hydrophobicity (CHFPC1). Based on HPLC characteristics, CHFPS1, CHFPW1, and CHFPC1 all could reflect the same molecule. That molecule could be interleukin 3 (IL 3), because IL 3, purified to homogeneity, was also found to function in the CHFP assay. In contrast, CHFPW2 and CHFPS2 had different hydrophobicities. Therefore, a possibility exists that there are a minimum number of three factors functional in the CHFP assay: IL 3, CHFPW2, and CHFPS2. Based on HPLC separations, CHFPS2 represents a molecule distinct from biochemically characterized cytokines implicated previously in the generation of CTL:CHF, CSF, interferon, and interleukins 1, 2, and 3. The killer cells stimulated are both virus-specific and H-2-restricted as is characteristic of CTL.
Functional and structural studies of the vaccinia virus virulence factor N1 reveal a Bcl-2-like anti-apoptotic protein (2007)

Vaccinia virus (VACV) encodes many immunomodulatory proteins, including inhibitors of apoptosis and modulators of innate immune signalling. VACV protein N1 is an intracellular homodimer that contributes to virus virulence and was reported to inhibit nuclear factor (NF)-kappaB signalling. However, analysis of NF-kappaB signalling in cells infected with recombinant viruses with or without the N1L gene showed no difference in NF-kappaB-dependent gene expression. Given that N1 promotes virus virulence, other possible functions of N1 were investigated and this revealed that N1 is an inhibitor of apoptosis in cells transfected with the N1L gene and in the context of VACV infection. In support of this finding virally expressed N1 co-precipitated with endogenous pro-apoptotic Bcl-2 proteins Bid, Bad and Bax as well as with Bad and Bax expressed by transfection. In addition, the crystal structure of N1 was solved to 2.9 A resolution (0.29 nm). Remarkably, although N1 shows no sequence similarity to cellular proteins, its three-dimensional structure closely resembles Bcl-x(L) and other members of the Bcl-2 protein family. The structure also reveals that N1 has a constitutively open surface groove similar to the grooves of other anti-apoptotic Bcl-2 proteins, which bind the BH3 motifs of pro-apoptotic Bcl-2 family members. Molecular modelling of BH3 peptides into the N1 surface groove, together with analysis of their physico-chemical properties, suggests a mechanism for the specificity of peptide recognition. This study illustrates the importance of the evolutionary conservation of structure, rather than sequence, in protein function and reveals a novel anti-apoptotic protein from orthopoxviruses.
Synthesis of 3‘-Fluoro-2‘,3‘-dideoxy-2‘,3‘-didehydro-4‘-ethynyl-d- and -l-furanosyl Nucleosides (2004)

An efficient procedure has been developed for the synthesis of 3'-fluoro-2',3'-dideoxy-2',3'-didehydro-4'-ethynyl D- and L-furanosyl nucleosides (1 and 2) starting from 2,3-O-isopropylidene-d-glyceraldehyde. The key intermediate 1-O-benzoyl-3E-fluoro-3,4-unsaturated-5,6-di(tert-butyldimethylsilyloxy)-2-hexanone 8 was obtained in nine steps with the overall yield of 22%. The alpha,beta-unsaturated ketone 8 was then treated with ethynylmagnesium bromide in a typical Grignard reaction procedure to afford the two intermediates 9 and 10, which after deprotection, oxidation, and acetylation gave the corresponding 4-ethynyl-substituted D- and L-sugar moieties 15 and 16, respectively. A series of D- and L-pyrimidine and purine nucleosides were prepared by the coupling of the sugar moieties with various silylprotected bases. The anomeric mixtures were obtained after condensation. After separation, the beta-isomers were further deprotected to yield the target nucleosides. All the newly synthesized 4'-substituted nucleosides were tested for their activities against HIV, among which the D-adenine derivative showed moderate anti-HIV activity (EC(50) = 25.1 microM) without significant cytotoxicity.
Robust superpoll protocol for IEEE 802.11 wireless LANs (2002)

As wireless local area networks (WLANs) are rapidly deployed to expand the field of wireless products in military settings, the provision of robust and efficient communication in the face of noisy environments will be mandatory. Such design needs to take into consideration the WLANs limited bandwidth and high error rates. We introduce the concept of super polling which can be implemented within the IEEE 802.11 Point Coordination Function (PCF) media access control scheme. We notice a dramatic throughput increase (up to 85%) when compared with the single poll mechanism used in IEEE 802.11 PCF. The throughput increase is measured as a function of the channel noise, the superpoll overhead per data packet and the packet size.
Preexisting Insulin Autoantibodies Predict Efficacy of Otelixizumab in Preserving Residual β-Cell Function in Recent-Onset Type 1 Diabetes (2015)

There is important specificity of IAA among other diabetes autoantibodies to predict good therapeutic response of recent-onset type 1 diabetic patients to anti-CD3 treatment. If confirmed, future immune intervention trials in type 1 diabetes should consider both relatively preserved functional β-cell mass and presence of IAA as inclusion criteria.
Identification of new biomarkers for clinical trials of Hsp90 inhibitors (2006)

The selective heat shock protein 90 (HSP90) inhibitor 17-allyamino-17-demethoxygeldanamycin (17-AAG) is currently in phase I/II clinical studies at numerous institutions. Heretofore, the biomarkers to detect 17-AAG bioactivity (Hsp70, Raf-1, and cyclin-dependent kinase 4) had to be analyzed by Western blot of cellular samples, either from tumor biopsies or peripheral blood leukocytes, a method that is both laborious and invasive. We have identified two new biomarkers [insulin-like growth factor binding protein-2 (IGFBP2) and HER-2 extracellular domain] that can be readily detected in patient sera by ELISA. Both secreted proteins are derived from or regulated by Hsp90 client proteins, raising hopes that they might be sensitive serum markers of HSP90 inhibitor activity. Several structurally unrelated HSP90 inhibitors dose-dependently decreased secretion of both IGFBP-2 and HER-2 extracellular domain into culture medium, and both proteins were more sensitive to HSP90 inhibitors than previously identified biomarkers. In sera from BT474 tumor-bearing mice, both IGFBP-2 and HER-2 extracellular domain were down-regulated by 17-AAG in a time-dependent and dose-dependent manner, coincident with the degradation of HER-2 and attenuation of AKT activity in the tumors. Furthermore, IGFBP-2 levels at the end of treatment correlated with residual tumor load, suggesting that IGFBP-2 might serve as an early indicator of therapeutic response. In addition, we also found that both IGFBP-2 and HER-2 extracellular domain levels are elevated in patient sera from several cancer types, suggesting that these novel secreted biomarkers could be valuable pharmacodynamic tools in clinical trials of HSP90 inhibitors.
Three-Dimensional Photonic Crystal Fluorinated Tin Oxide (FTO) Electrodes: Synthesis and Optical and Electrical Properties (2011)

Photovoltaic (PV) schemes often encounter a pair of fundamentally opposing requirements on the thickness of semiconductor layer: a thicker PV semiconductor layer provides enhanced optical density, but inevitably increases the charge transport path length. An effective approach to solve this dilemma is to enhance the interface area between the terminal electrode, i.e., transparent conducting oxide (TCO) and the semiconductor layer. As such, we report a facile, template-assisted, and solution chemistry-based synthesis of 3-dimensional inverse opal fluorinated tin oxide (IO-FTO) electrodes. Synergistically, the photonic crystal structure possessed in the IO-FTO exhibits strong light trapping capability. Furthermore, the electrical properties of the IO-FTO electrodes are studied by Hall effect and sheet resistance measurement. Using atomic layer deposition method, an ultrathin TiO(2) layer is coated on all surfaces of the IO-FTO electrodes. Cyclic voltammetry study indicates that the resulting TiO(2)-coated IO-FTO shows excellent potentials as electrodes for electrolyte-based photoelectrochemical solar cells.
Phase modelling of speech excitation for low bit-rate sinusoidal transform coding (2002)

Sinusoidal transform coding (STC) techniques model speech as the sum of sine-waves whose frequencies, amplitudes and phases are specified at regular intervals. To achieve a low-bit rate representation, only the spectral envelope is encoded and the phases are regenerated according to a minimum phase assumption. In this paper, the inaccuracy of the minimum phase model is demonstrated. It is shown that the phase spectra of decoded speech segments may be corrected using either the parameters of a Rosenberg pulse model or a second order all-pass filter. Experiments have shown that by applying this correction, the phase accuracy increases and the speech quality improves.
Allosteric enzymes as biosensors for molecular diagnosis (2003)

Biosensors are hybrid analytical devices that amplify signals generated from the specific interaction between a receptor and the analyte, through a biochemical mechanism. Biosensors use tissues, whole cells, artificial membranes or cell components like proteins or nucleic acids as receptors, coupled to a physicochemical signal transducer. Allosteric enzymes exhibit a catalytic activity that is modulated by specific effectors, through binding to receptor sites that are distinct from the active site. Several enzymes, catalyzing easily measurable reactions, have been engineered to allosterically respond to specific ligands, being themselves the main constituent of new-generation biosensors. The molecular basis, robustness and application of allosteric enzymatic biosensing are revised here.
Differential Targeting of β-Adrenergic Receptor Subtypes and Adenylyl Cyclase to Cardiomyocyte Caveolae (2000)

Differential modes for beta(1)- and beta(2)-adrenergic receptor (AR) regulation of adenylyl cyclase in cardiomyocytes is most consistent with spatial regulation in microdomains of the plasma membrane. This study examines whether caveolae represent specialized subdomains that concentrate and organize these moieties in cardiomyocytes. Caveolae from quiescent rat ventricular cardiomyocytes are highly enriched in beta(2)-ARs, Galpha(i), protein kinase A RIIalpha subunits, caveolin-3, and flotillins (caveolin functional homologues); beta(1)-ARs, m(2)-muscarinic cholinergic receptors, Galpha(s), and cardiac types V/VI adenylyl cyclase distribute between caveolae and other cell fractions, whereas protein kinase A RIalpha subunits, G protein-coupled receptor kinase-2, and clathrin are largely excluded from caveolae. Cell surface beta(2)-ARs localize to caveolae in cardiomyocytes and cardiac fibroblasts (with markedly different beta(2)-AR expression levels), indicating that the fidelity of beta(2)-AR targeting to caveolae is maintained over a physiologic range of beta(2)-AR expression. In cardiomyocytes, agonist stimulation leads to a marked decline in the abundance of beta(2)-ARs (but not beta(1)-ARs) in caveolae. Other studies show co-immunoprecipitation of cardiomyocytes adenylyl cyclase V/VI and caveolin-3, suggesting their in vivo association. However, caveolin is not required for adenylyl cyclase targeting to low density membranes, since adenylyl cyclase targets to low buoyant density membrane fractions of HEK cells that lack prototypical caveolins. Nevertheless, cholesterol depletion with cyclodextrin augments agonist-stimulated cAMP accumulation, indicating that caveolae function as negative regulators of cAMP accumulation. The inhibitory interaction between caveolae and the cAMP signaling pathway as well as domain-specific differences in the stoichiometry of individual elements in the beta-AR signaling cascade represent important modifiers of cAMP-dependent signaling in the heart.
LEDGINs inhibit late stage HIV-1 replication by modulating integrase multimerization in the virions (2013)

Our results suggest that LEDGINs modulate IN multimerization in progeny virions and impair the formation of regular cores during the maturation step, resulting in a decreased infectivity of the viral particles in the target cells. LEDGINs thus profile as unique antivirals with combined early (integration) and late (IN assembly) effects on the HIV replication cycle.
Low level laser irradiation precondition to create friendly milieu of infarcted myocardium and enhance early survival of transplanted bone marrow cells (2009)

We suggested that low-level laser irradiation (LLLI) precondition prior to cell transplantation might remodel the hostile milieu of infarcted myocardium and subsequently enhance early survival and therapeutic potential of implanted bone marrow mesenchymal stem cells (BMSCs). Therefore, in this study we wanted to address: (1) whether LLLI pre-treatment change the local cardiac micro-environment after myocardial infarction (MI) and (2) whether the LLLI preconditions enhance early cell survival and thus improve therapeutic angiogenesis and heart function. MI was induced by left anterior descending artery ligation in female rats. A 635 nm, 5 mW diode laser was performed with energy density of 0.96 J/cm(2) for 150 sec. for the purpose of myocardial precondition. Three weeks later, qualified rats were randomly received with LLLI precondition (n= 26) or without LLLI precondition (n= 27) for LLLI precondition study. Rats that received thoracotomy without coronary ligation were served as sham group (n= 24). In the cell survival study, rats were randomly divided into 4 groups: serum-free culture media injection (n= 8), LLLI precondition and culture media injection (n= 8), 2 million male BMSCs transplantation without LLLI pre-treatment (n= 26) and 2 million male BMSCs transplantation with LLLI precondition (n= 25) group, respectively. Vascular endothelial growth factor (VEGF), glucose-regulated protein 78 (GRP78), superoxide dismutase (SOD) and malondialdehyde (MDA) in the infarcted myocardium were evaluated by Western blotting, real-time PCR and colorimetry, respectively, at 1 hr, 1 day and 1 week after laser irradiation. Cell survival was assayed with quantitative real-time PCR to identify Y chromosome gene and apoptosis was assayed with transferase-mediated dUTP end labelling staining. Capillary density, myogenic differentiation and left ventricular function were tested by immunohistochemistry and echocardiography, respectively, at 1 week. After LLLI precondition, increased VEGF and GRP78 expression, as well as the enhanced SOD activity and inhibited MDA production, was observed. Compared with BMSC transplantation and culture media injection group, although there was no difference in the improved heart function and myogenic differentiation, LLLI precondition significantly enhanced early cell survival rate by 2-fold, decreased the apoptotic percentage of implanted BMSCs in infarcted myocardium and thus increased the number of newly formed capillaries. Taken together, LLLI precondition could be a novel non-invasive approach for intraoperative cell transplantation to enhance cell early survival and therapeutic potential.
Valvular Heart Disease (2008)

This chapter contains sections titled: Introduction Echocardiography Quantification of severity of valve disease Endocarditis prophylaxis Rheumatic fever prophylaxis Specific valve lesions Future directions
Causation: a user's guide (2014)

Preface 1. The scope and aims of this guide 2. Framework and preliminaries 3. Varieties of redundant causation 4. Causation involving omissions 5. Cases that threaten transitivity 6. Concluding remarks References Index
Therapy for Human Immunodeficiency Virus Infection (1993)

Much is known about the replication of the human immunodeficiency virus type 1 (HIV-1) from the time of cell attachment to the release of mature virions (Figure 1), and drugs that interfere with many of the steps in HIV replication have been developed and tested in vitro. These drugs include inhibitors of reverse transcriptase, protease, and a regulatory protein, Tat (Table 1). Inhibitors of reverse transcriptase can prevent the spread of infectious virus to new cells but do not interfere with the replication of HIV genomes that are integrated into the host genome. Two of the most promising agents target . . .
Selective expression of carcinoembryonic antigen promoter in cancer cell lines (1998)

The expression of pCEA correlates well with the CEA production by the specific cell line offering a potential tissue-specific targeting strategy for colon cancer gene therapy. Furthermore, the tissue-specific CEA promoter has a higher and more persistent activity in CEA-positive human cancer cells than a viral promoter. The lack of response to interferon-gamma treatment suggests a different mechanism of action for interferon-gamma other than directly interacting with the promoter.