gebhart/patrepeval huggingface dataset:
New Synthetic Triterpenoids: Potent Agents for Prevention and Treatment of Tissue Injury Caused by Inflammatory and Oxidative Stress (2011)

We review the original rationale for the development and the chemistry of a series of new synthetic oleanane triterpenoids (SO), based on oleanolic acid (1) as a starting material. Many of the new compounds that have been made, such as 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid ("CDDO", 8), are highly potent (activities found at levels below 1 nM) anti-inflammatory agents, as measured by their ability to block the cellular synthesis of the enzyme inducible nitric oxide synthase (iNOS) in activated macrophages. Details of the organic synthesis of new SO and their chemical mechanisms of biological activity are reviewed, as is formation of biotin conjugates for investigation of protein targets. Finally, we give a brief summary of important biological activities of SO in many organ systems in numerous animal models. Clinical investigation of a new SO (methyl 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate, "CDDO-Me", bardoxolone methyl, 13) is currently in progress.
Silicon realization of an OFDM synchronization algorithm (2003)

In this paper a hardware architecture for an OFDM synchronizer is presented. The proposed synchronization unit can be used in any OFDM system that uses a cyclic prefix. The algorithm is based on the correlation introduced by the cyclic prefix, which is exploited in the time domain where both time and frequency offset are estimated simultaneously. The synchronization unit also performs frequency correction, which means that no feedback to the analog parts is necessary. Although the algorithm is too complex to be implemented on today's most powerful standard DSP, a hardware architecture that is optimized for the algorithm can be implemented with moderate complexity. The unit contains 32 kbit RAM and 5000 gates and the sample rate is 25 Msamples/s.
Identification of a Binding Site for Glycoprotein Ibα in the Apple 3 Domain of Factor XI (2004)

Factor XI (FXI) is a homodimeric plasma zymogen that is cleaved at two internal Arg(369)-Ile(370) bonds by thrombin, factor XIIa, or factor XIa. FXI circulates as a complex with the glycoprotein high molecular weight kininogen (HK). FXI binds to specific sites (K(d) = approximately 10 nM, B(max) = approximately 1,500/platelet) on the surface of stimulated platelets, where it is efficiently activated by thrombin. The FXI Apple 3 (A3) domain mediates binding to platelets in the presence of HK and zinc ions (Zn(2+)) or prothrombin and calcium ions. The platelet glycoprotein (GP) Ib-IX-V complex is the receptor for FXI. Using surface plasmon resonance, we determined that FXI binds specifically to glycocalicin, the extracellular domain of GPIbalpha, in a Zn(2+)-dependent fashion (K(d) = approximately 52 nM). We now show that recombinant FXI A3 domain inhibits FXI inbinding to glycocalicin in the presence of Zn(2+), whereas the recombinant FXI A1, A2, or A4 domains have no effect. Experiments with full-length recombinant FXI mutants show that, in the presence of Zn(2+), glycocalicin binds FXI at a heparin-binding site in A3 (Lys(252) and Lys(253)) and not by amino acids previously shown to be required for platelet binding (Ser(248), Arg(250), Lys(255), Phe(260), and Gln(263)). However, binding in the presence of HK and Zn(2+) requires Ser(248), Arg(250), Lys(255), Phe(260), and GLn(263) and not Lys(252) and Lys(253). Thus, binding of FXI to GPIbalpha is mediated by amino acids in the A3 domain in the presence or absence of HK. This interaction is important for the initiation of the consolidation phase of blood coagulation and the generation of thrombin at sites of platelet thrombus formation.
Ets-1 is an early response gene activated by ET-1 and PDGF-BB in vascular smooth muscle cells (1998)

Ets-1 is a transcription factor that activates expression of matrix-degrading proteinases such as collagenase and stromelysin. To study the control of ets-1 gene expression in rat vascular smooth muscle cells (VSMC), cells were exposed to factors known to regulate VSMC migration and proliferation. Platelet-derived growth factor-BB (PDGF-BB), endothelin-1 (ET-1), and phorbol 12-myristate 13-acetate (PMA) induced a dose-dependent expression of ets-1 mRNA. These effects were abrogated by inhibition of protein kinase C (PKC) by H-7 or chronic PMA treatment. Ets-1 mRNA was superinduced by PDGF-BB and ET-1 in the presence of cycloheximide. The chelation of intracellular Ca2+ by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester and the depletion of endoplasmic reticulum intracellular Ca2+ concentration ([Ca2+]i) by thapsigargin inhibited PDGF-BB- and ET-1-induced ets-1 mRNA, whereas ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid had no effect. However, [Ca2+]i release alone was not sufficient to increase ets-1 mRNA. Forskolin blocked ET-1-, PDGF-BB-, and PMA-induced ets-1 mRNA, as well as inositol phosphate formation, consistent with an effect through impairment of PKC activation. Inhibitors of ets-1 gene expression, such as H-7 and herbimycin A, inhibited the ET-1 induction of collagenase I mRNA. We propose that ets-1 may be an important element in the orchestration of matrix proteinase expression and of vascular remodeling after arterial injury.
Defining the Cellular Target(s) of Porcine Reproductive and Respiratory Syndrome Virus Blocking Monoclonal Antibody 7G10 (2005)

We produced a monoclonal antibody (MAb) (7G10) that has blocking activity against porcine reproductive and respiratory syndrome virus (PRRSV). In this study, we identified the components of the 7G10 MAb-bound complex as cytoskeletal filaments: vimentin, cytokeratin 8, cytokeratin 18, actin, and hair type II basic keratin. Vimentin bound to PRRSV nucleocapsid protein and anti-vimentin antibodies showed PRRSV-blocking activity. Vimentin was expressed on the surface of MARC-145, a PRRSV-susceptible cell line. Simian vimentin rendered BHK-21 and CRFK, nonsusceptible cell lines, susceptible to PRRSV infection. These results suggest that vimentin is part of the PRRSV receptor complex and that it plays an important role in PRRSV binding with the other cytoskeletal filaments that mediate transportation of the virus in the cytosol.
SiGe-on-insulator substrate using SiGe alloy grown Si(001) (1999)

Low-energy oxygen ion (25 keV O+) implantation was performed on a pseudomorphic Si1−xGex/Si(001) of uniform composition in an attempt to create a SiGe-on-insulator (SiGe-OI) substrate using the separation-by-implanted-oxygen technique. Choosing a small Ge composition (&amp;lt;0.3) was found to be essential to achieving a SiGe-OI geometry of structural integrity.
Overproduction of Escherichia coli integration host factor, a protein with nonidentical subunits (1987)

Integration host factor (IHF) is a small, basic protein that is needed for efficient recombination of bacteriophage lambda, as well as for other host and viral functions. We have constructed strains in which the two subunits of IHF, encoded by the himA and hip genes of Escherichia coli, are expressed under the control of the lambda rho L promoter. Separate overexpression of himA and hip led to the production of unstable and insoluble peptides, respectively. In contrast, the overexpression of both genes conjointly led to the accumulation of large amounts of active IHF. Extracts of such cells provided the starting material for a rapid purification procedure that results in milligram quantities of apparently homogeneous IHF.
Characterization of the 3‘ → 5‘ Exonuclease Activity Found in Human Nucleoside Diphosphate Kinase 1 (NDK1) and Several of Its Homologues (2005)

Nucleoside diphosphate kinases (NDKs), an evolutionarily conserved family of proteins, synthesize nucleoside triphosphates from nucleoside diphosphates and ATP. Here, we have characterized the kinase activity and DNA processing functions of eight human proteins that contain at least one domain homologous to Escherichia coli NDK. Not all human proteins with NDK-like domains exhibited NDK activity when expressed as recombinant proteins in E. coli. Human NDK1 (NM23-H1) has been reported to have 3' --> 5' exonuclease activity. In addition to human NDK1, we also find that human NDK5, NDK7, and NDK8 contain 3' --> 5' exonuclease activity. Site-directed mutagenesis, competition assays between wild-type and mutant NDK proteins, and NMR studies confirmed that the DNA-binding and 3' --> 5' exonuclease activity of human NDK1 is an intrinsic activity of the protein. Using double-stranded DNA substrates containing modified bases, human NDK1 efficiently excised nucleotides from the single-strand break produced by APE1 or Nth1. When human cells were treated with various DNA-damaging agents, human NDK1 translocated from the cytoplasm to the nucleus. These results suggest that, in addition to maintenance of nucleotide pool balance, the human NDK-like proteins may have previously unrecognized roles in DNA nucleolytic processing.
Self-organization of jets in electrospinning from free liquid surface: A generalized approach (2008)

Electrospinning has enabled creation of excellent materials for a great number of applications. Previously, it was based on less productive capillary spinners. The present study is based on recent efforts to elevate electrospinning technology to an industrial level by simultaneously provoking innumerable polymeric jets from a sufficiently large liquid surface to increase productivity. Particularly, it deals with electrospinning from free surface of conductive liquids and validates a formulated hypothesis that explains self-organization of jets on one-dimensional free liquid surfaces in terms of electrohydrodynamic instability of surface waves. Here, it is shown how the hypothesis, based on a profound analysis of a dispersion law, explains that above a certain critical value of applied electric field intensity∕field strength the system starts to be self-organized in mesocopic scale due to the mechanism of the “fastest forming instability.” The mechanism plays a key role in selecting a particular wave with a characteristic wavelength whose amplitude boundlessly grows faster than the others. The fastest growing stationary wave, according to the hypothesis, marks the onset of electrospinning from a free liquid surface with its jets originating from the wave crests. Singularity of this approach lies in predicting critical values of the phenomenon, viz., critical field strength and corresponding critical interjet distance. The critical field strength, will, thereafter, be used in defining a unique dimensionless electrospinning number. It will, subsequently, be shown how the critical interjet distance, i.e., the maximal distance between the neighboring jets, simply depends on the capillary length. The capillary length represents a latent characteristic spatial scale of the system. The theory also predicts interjet distance for field strengths above the critical value. The said prediction is universally applicable for all conductive liquids if it is expressed in terms of the dimensionless parameters of the interjet distance and the electrospinning number. The theory also predicts relaxation time, necessary for spontaneous jetting after a high voltage is applied. The theoretical considerations are eventually compared to that of Zeleny’s, obtained for capillary electrospinner to demonstrate universality of the approach. Eventually, jetting from free liquid surface on specially designed linear cleft electrospinner are observed, analyzed, and compared to the theoretical predictions obtaining satisfactory results.
Is Gut Microbiota Dysbiosis a Predictor of Increased Susceptibility to Poor Outcome of COVID-19 Patients? An Update (2020)

The scientific knowledge already attained regarding the way severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells and the clinical manifestations and consequences for Coronavirus Disease 2019 (COVID-19) patients, especially the most severe cases, brought gut microbiota into the discussion. It has been suggested that intestinal microflora composition plays a role in this disease because of the following: (i) its relevance to an efficient immune system response; (ii) the fact that 5-10% of the patients present gastrointestinal symptoms; and (iii) because it is modulated by intestinal angiotensin-converting enzyme 2 (ACE2) (which is the virus receptor). In addition, it is known that the most severely affected patients (those who stay longer in hospital, who require intensive care, and who eventually die) are older people with pre-existing cardiovascular, metabolic, renal, and pulmonary diseases, the same people in which the prevalence of gut microflora dysbiosis is higher. The COVID-19 patients presenting poor outcomes are also those in which the immune system's hyperresponsiveness and a severe inflammatory condition (collectively referred as "cytokine storm") are particularly evident, and have been associated with impaired microbiota phenotype. In this article, we present the evidence existing thus far that may suggest an association between intestinal microbiota composition and the susceptibility of some patients to progress to severe stages of the disease.
Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis (2006)

Ubiquitin-positive, tau- and alpha-synuclein-negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders. Pathologic TDP-43 was hyper-phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments and was recovered only from affected central nervous system regions, including hippocampus, neocortex, and spinal cord. TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders.
Pharmacological and functional characterization of muscarinic receptor subtypes in developing oligodendrocytes (2001)

This study focused on the molecular and pharmacological characterization of muscarinic acetylcholine receptors expressed by progenitors and differentiated oligodendrocytes. We also analyzed the role of muscarinic receptors in regulating downstream signal transduction pathways and the functional significance of receptor expression in oligodendrocytes. RT-PCR analysis revealed the expression of transcripts for M3, and to a lesser extent M4, followed by M1, M2 and M5 receptor subtypes in both progenitors and differentiated oligodendrocytes. Competition binding experiments using [(3)H]N-methylscopolamine and several antagonists, as well as inhibition of carbachol-mediated phosphoinositide hydrolysis, showed that M3 is the main subtype expressed in these cells. In progenitors the activation of p42/44-mitogen-activated protein kinase (MAPK) and cAMP-response element binding protein (CREB) as well as c-fos mRNA expression were blocked by the M3 relatively selective antagonist, 4-DAMP, and its irreversible analogue, 4-DAMP-mustard. Carbachol increased proliferation of progenitors, an effect prevented by atropine and 4-DAMP, as well as by the MAPK kinase inhibitor PD98059. These results indicate that carbachol modulates oligodendrocyte progenitor proliferation through M3 receptors, involving activation of a MAPK signaling pathway. Receptor density and phosphoinositide hydrolysis are down-regulated during oligodendrocyte differentiation. Functional consequences of these events are a reduction in carbachol-stimulated p42/44(MAPK) and CREB phosphorylation, as well as induction of c-fos.
Hematopoietic responses to stress conditions in young dogs compared with elderly dogs (2001)

Clinical observations show that older patients do not tolerate high-dose chemoradiotherapy as well as younger patients. It is unclear whether this is due to age-related differences in their responses to hematopoietic injury or to differential toxicities to other organs. In the present study, 6 young (0.5 years) and 6 elderly (8 years) dogs were challenged with 7 repeated nonlethal doses of 50 or 100 cGy total body irradiation (TBI) each (total 550 cGy), and 21 days of recombinant canine granulocyte-colony stimulating factor (rcG-CSF) after the last TBI dose. Recoveries of absolute neutrophil, platelet, and lymphocyte counts after each TBI dose, responses to rcG-CSF treatment, and telomere lengths in neutrophils were compared before and after the study. No differences were found in recoveries of neutrophils, platelets, or in responses to rcG-CSF among young and old dogs. In contrast, recoveries were suggestively worse in younger dogs. After rcG-CSF, platelet recoveries were poor in both groups compared with previous platelet recoveries (P <.01). Consequently, 2 old and 3 young dogs were euthanized because of persistent thrombocytopenia and bleeding. At the study's completion, marrow cellularities and peripheral blood counts of the remaining young and elderly dogs were equivalent. The telomere lengths in both groups were significantly reduced after the study versus beforehand (P =.03), but the median attritions of telomeres were not different. It was concluded that aging does not appear to affect hematopoietic cell recoveries after repeated low-dose TBI, suggesting that poor tolerance of radiochemotherapy regimens in older patients may be due to nonhematopoietic organ toxicities rather than age-related changes in hematopoietic stem cells reserves.
Hierarchical Forecasting of Web Server Workload Using Sequential Monte Carlo Training (2007)

Internet service utilities host multiple server applications on a shared server cluster (server farm). One of the essential tasks of the hosting service provider is to allocate servers to each of the websites to maintain a certain level of quality of service for different classes of incoming requests at each point of time, and optimize the use of server resources, while maximizing its profits. Such a proactive management of resources requires accurate prediction of workload, which is generally measured as the amount of service requests per unit time. As a time series, the workload exhibits not only short time random fluctuations but also prominent periodic (daily) patterns that evolve randomly from one period to another. We propose a solution to the Web server load prediction problem based on a hierarchical framework with multiple time scales. This framework leads to adaptive procedures that provide both long-term (in days) and short-term (in minutes) predictions with simultaneous confidence bands which accommodate not only serial correlation but also heavy-tailedness, and nonstationarity of the data. The long-term load is modeled as a dynamic harmonic regression (DHR), the coefficients of which evolve according to a random walk, and are tracked using sequential Monte Carlo (SMC) algorithms; whereas the short-term load is predicted using an autoregressive model, whose parameters are also estimated using SMC techniques. We evaluate our method using real-world Web workload data
Receptor binding specificities of Herstatin and its intron 8‐encoded domain (2004)

Retention of intron 8 in alternative HER-2 mRNA generates an inhibitory secreted ligand, Herstatin, with a novel receptor-binding domain (RBD) encoded by the intron. This study examines binding interactions with several receptors and investigates sequence variations in intron 8. The RBD, expressed as a peptide, binds at nM concentrations to HER-2, the EGFR, DeltaEGFR, HER-4 and to the IGF-1 receptor, but not to HER-3 nor to the FGF-3 receptor, whereas a rare mutation in the RBD (Arg to Ile) eliminates receptor binding. The full-length Herstatin binds with 3-4-fold higher affinity than its RBD, but with approximately 10-fold lower affinity to the IGF-IR. Sequence conservation in rhesus monkey but not in rat suggests that intron 8 recently diverged as a receptor-binding module critical for the function of Herstatin.
Fertile Hypomorphic ARGONAUTE (ago1) Mutants Impaired in Post-Transcriptional Gene Silencing and Virus Resistance (2002)

Transgene-induced post-transcriptional gene silencing (PTGS) results from specific degradation of RNAs that are homologous with the transgene transcribed sequence. This phenomenon, also known as cosuppression in plants and quelling in fungi, resembles RNA interference (RNAi) in animals. Indeed, cosuppression/quelling/RNAi require related PAZ/PIWI proteins (AGO1/QDE-2/RDE-1), indicating that these mechanisms are related. Unlike Neurospora crassa qde-2 and Caenorhabditis elegans rde-1 mutants, which are morphologically normal, the 24 known Arabidopsis ago1 mutants display severe developmental abnormalities and are sterile. Here, we report the isolation of hypomorphic ago1 mutants, including fertile ones. We show that these hypomorphic ago1 mutants are defective for PTGS, like null sgs2, sgs3, and ago1 mutants, suggesting that PTGS is more sensitive than development to perturbations in AGO1. Conversely, a mutation in ZWILLE/PINHEAD, another member of the Arabidopsis AGO1 gene family, affects development but not PTGS. Similarly, mutations in ALG-1 and ALG-2, two members of the C. elegans RDE-1 gene family, affect development but not RNAi, indicating that the control of PTGS/RNAi and development by PAZ/PIWI proteins can be uncoupled. Finally, we show that hypomorphic ago1 mutants are hypersensitive to virus infection, confirming the hypothesis that in plants PTGS is a mechanism of defense against viruses.
Use of Interferon for Prevention of Hepatocellular Carcinoma in Cirrhotic Patients with Hepatitis B or Hepatitis C Virus Infection (1999)

The incidence of hepatocellular carcinoma in North America is increasing. Current debate focuses on whether interferon administered to cirrhotic patients-with or without biochemical or virologic response-delays or prevents cancer of the liver. Review of the literature revealed several studies that showed improvement in or delay in progression of histologic fibrosis in patients with hepatitis C virus (HCV) infection. In patients with hepatitis B virus (HBV) infection, conversion to the nonreplicative stage may be associated with histologic improvement. However, only 11 studies (6 of HCV, 3 of HBV, and 2 of HCV and HBV) compared development of hepatocellular carcinoma in interferon-treated patients with cirrhosis and cirrhotic patients who were not treated with interferon. Although no firm statistical conclusions could be drawn, the literature suggests that interferon therapy may prevent hepatocellular carcinoma in patients with cirrhosis, particularly those infected with HCV. Interferon treatment cannot be recommended for all persons with cirrhosis and HBV or HCV infection because the current evidence is only suggestive. Long-term randomized, controlled trials may provide definitive data; however, it will be difficult, if not impossible, to conduct such trials because of the improved efficacy of combination therapy with interferon and ribavirin in patients with chronic HCV infection and the development of new therapies for patients with HBV infection.
Off-resonance excitation in a linear ion trap (2008)

Off-resonance excitation coupled with mass-selective axial ejection of ions in a linear ion trap is shown to allow coherent control of a trapped ion population. Oscillations of the detected ion current have been found to correspond to the degree of detuning of the excitation field from the resonance frequency. Under appropriate excitation conditions coherent oscillations at the excitation frequency are seen that evolve into the ions' secular frequency on termination of the excitation field. Termination of the excitation field at various points during the off-resonance excitation profile leaves the ions with different degrees of radial excitation. The degree of radial excitation can be controlled by the coherent excitation field and is demonstrated to be useful for collision-induced dissociation.