gebhart/patrepeval huggingface dataset:
Light-induced acceleration of photoreceptor degeneration in transgenic mice expressing mutant rhodopsin. (1996)

These findings suggest that light activation of rhodopsin contributes to the severity of the degenerative disease resulting from the P23H opsin mutation, and they raise the possibility that minimizing exposure to light may help to prolong useful vision of patients with this form of retinitis pigmentosa.
The parkinsonian toxin MPTP: action and mechanism (2000)

MPTP causes damage to substantia nigra pars compacta (SNpc) dopaminergic (DA) neurons as seen in Parkinson's disease (PD). After sys-temic administration of MPTP, its active metabolite, MPP +, accumulates within SNpc DA neurons, where it inhibits ATP production and stim-ulates superoxide radical formation. The produced superoxide radicals react with nitric oxide (NO) to produce peroxynitrite, a highly reactive tissue-damaging species that damages proteins by oxidation and nitration. Only selected proteins appear nitrated, and among these, is found tyrosine hydroxylase (TH), the rate limiting enzyme in DA synthesis. The process of nitration inactivates TH and, consequently dopamine pro-duction. Peroxynitrite also nicks DNA, which, in turn, activates poly(ADP-ribose) polymerase (PARP). PARP activation consumes ATP, and thus acutely depletes cell energy stores. This latter event aggravates the preexisting energy failure due to MPP + -induced mitochondrial respira-tion blockade and precipitates cell death. Altogether, these findings support the view that MPTP's deleterious cascade of events include mito-chondrial respiration deficit, oxidative stress, and energy failure. Because of the similarity between the MPTP mouse model and PD, it is tempting to propose that a similar scenario applies to the pathogenesis of PD.
The Parasympathetic Nervous System in the Quest for Stroke Therapeutics (2011)

Stroke is a devastating neurovascular disease with limited therapeutic options. The pathogenesis of stroke involves complex interrelated molecular mechanisms including excitotoxicity, oxidative and nitrosative stress, cortical spreading depolarizations, inflammation, necrosis, and apoptosis. Successful development of stroke therapeutics depends on understanding these molecular mechanisms and how to counteract them to limit tissue damage during stroke. Activation of the parasympathetic nervous system (PNS) has been shown to antagonize a multiplicity of pathologic mechanisms. Elements of parasympathetic activation such as vagus nerve stimulation have already been used successfully in treating brain disorders such as epilepsy and depression. This review discusses the anatomical basis and molecular mechanisms involved in activation of the PNS, and assesses the strength of available evidence for the further development of this modality into a stroke therapy.
Cytosolic galectin-7 impairs p53 functions and induces chemoresistance in breast cancer cells (2014)

These findings pose a challenge to the paradigm that has guided the design of galectin-specific inhibitors for the treatment of cancer. This study suggests that targeting CRD-independent cytosolic gal-7 in breast cancer cells may be a valuable strategy for the treatment of this disease. Our study will thus complement efforts towards improving selectivity of targeted anticancer agents.
Disruption of the HIV‐1 protease dimer with interface peptides: Structural studies using NMR spectroscopy combined with [2‐13C]‐Trp selective labeling (2007)

HIV-1 protease (HIV-1 PR), which is encoded by retroviruses, is required for the processing of gag and pol polyprotein precursors, hence it is essential for the production of infectious viral particles. In vitro inhibition of the enzyme results in the production of progeny virions that are immature and noninfectious, suggesting its potential as a therapeutic target for AIDS. Although a number of potent protease inhibitor drugs are now available, the onset of resistance to these agents due to mutations in HIV-1 PR has created an urgent need for new means of HIV-1 PR inhibition. Whereas enzymes are usually inactivated by blocking of the active site, the structure of dimeric HIV-1 PR allows an alternative inhibitory mechanism. Since the active site is formed by two half-enzymes, which are connected by a four-stranded antiparallel beta-sheet involving the N- and C- termini of both monomers, enzyme activity can be abolished by reagents targeting the dimer interface in a region relatively free of mutations would interfere with formation or stability of the functional HIV-1 PR dimer. This strategy has been explored by several groups who targeted the four-stranded antiparallel beta-sheet that contributes close to 75% of the dimerization energy. Interface peptides corresponding to native monomer N- or C-termini of several of their mimetics demonstrated, mainly on the basis of kinetic analyses, to act as dimerization inhibitors. However, to the best of our knowledge, neither X-ray crystallography nor NMR structural studies of the enzyme-inhibitor complex have been performed to date. In this article we report a structural study of the dimerization inhibition of HIV-1 PR by NMR using selective Trp side chain labeling.
Effect of Ovarian Cancer Ascites on Cell Migration and Gene Expression in an Epithelial Ovarian Cancer In Vitro Model (2010)

A third of patients with epithelial ovarian cancer (EOC) present ascites. The cellular fraction of ascites often consists of EOC cells, lymphocytes, and mesothelial cells, whereas the acellular fraction contains cytokines and angiogenic factors. Clinically, the presence of ascites correlates with intraperitoneal and retroperitoneal tumor spread. We have used OV-90, a tumorigenic EOC cell line derived from the malignant ascites of a chemonaive ovarian cancer patient, as a model to assess the effect of ascites on migration potential using an in vitro wound-healing assay. A recent report of an invasion assay described the effect of ascites on the invasion potential of the OV-90 cell line. Ascites sampled from 31 ovarian cancer patients were tested and compared with either 5% fetal bovine serum or no serum for their nonstimulatory or stimulatory effect on the migration potential of the OV-90 cell line. A supervised analysis of data generated by the Affymetrix HG-U133A GeneChip identified differentially expressed genes from OV-90 cells exposed to ascites that had either a nonstimulatory or a stimulatory effect on migration. Ten genes (IRS2, CTSD, NRAS, MLXIP, HMGCR, LAMP1, ETS2, NID1, SMARCD1, and CD44) were upregulated in OV-90 cells exposed to ascites, allowing a nonstimulatory effect on cell migration. These findings were validated by quantitative polymerase chain reaction. In addition, the gene expression of IRS2 and MLXIP each correlated with prognosis when their expression was assessed in an independent set of primary cultures established from ovarian ascites. This study revealed novel candidates that may play a role in ovarian cancer cell migration.
Nickel-catalyzed displacement reactions of aryl halides (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNickel-catalyzed displacement reactions of aryl halidesRichard Cramer and D. Robert CoulsonCite this: J. Org. Chem. 1975, 40, 16, 2267–2273Publication Date (Print):August 1, 1975Publication History Published online1 May 2002Published inissue 1 August 1975https://doi.org/10.1021/jo00904a001Request reuse permissionsArticle Views862Altmetric-Citations85LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (926 KB) Get e-Alertsclose Get e-Alerts
A Principal Role for the Proteasome in Endoplasmic Reticulum-associated Degradation of Misfolded Intracellular Cystic Fibrosis Transmembrane Conductance Regulator (2002)

Endoplasmic reticulum-associated degradation of misfolded cystic fibrosis transmembrane conductance regulator (CFTR) protein is known to involve the ubiquitin-proteasome system. In addition, an ATP-independent proteolytic system has been suggested to operate in parallel with this pathway and become up-regulated when proteasomes are inhibited (Jensen, T. J., Loo, M. A., Pind, S., Williams, D. B., Goldberg, A. L., and Riordan, J. R. (1995) Cell 83, 129-135). In this study, we use two independent techniques, pulse-chase labeling and a noninvasive fluorescence cell-based assay, to investigate the proteolytic pathways underlying the degradation of misfolded CFTR. Here we report that only inhibitors of the proteasome have a significant effect on preventing the degradation of CFTR, whereas cell-permeable inhibitors of lysosomal degradation, autophagy, and several classes of protease had no measurable effect on CFTR degradation, when used either alone or in combination with the specific proteasome inhibitor carbobenzoxy-l-leucyl-leucyl-l-leucinal (MG132). Our results suggest that ubiquitin-proteasome-mediated degradation is the dominant pathway for disposal of misfolded CFTR in mammalian cells and provide new mechanistic insight into endoplasmic reticulum-associated degradation.
Parkin Mono-ubiquitinates Bcl-2 and Regulates Autophagy (2010)

Parkin is an E3 ubiquitin ligase that mediates the ubiquitination of protein substrates. The mutations in the parkin gene can lead to a loss of function of parkin and cause autosomal recessive juvenile onset parkinsonism. Recently, parkin was reported to be involved in the regulation of mitophagy. Here, we identify the Bcl-2, an anti-apoptotic and autophagy inhibitory protein, as a substrate for parkin. Parkin directly binds to Bcl-2 via its C terminus and mediates the mono-ubiquitination of Bcl-2, which increases the steady-state levels of Bcl-2. Overexpression of parkin, but not its ligase-deficient forms, decreases autophagy marker LC3 conversion, whereas knockdown of parkin increases LC3 II levels. In HeLa cells, a parkin-deficient cell line, knockdown of parkin does not change LC3 conversion. Moreover, overexpression of parkin enhances the interactions between Bcl-2 and Beclin 1. Our results provide evidence that parkin mono-ubiquitinates Bcl-2 and regulates autophagy via Bcl-2.
Speeding up protocols for small messages (1996)

Many techniques have been discovered to improve performance of bulk data transfer protocols which use large messages. This paper describes a technique that improves protocol performance for protocols that use small messages, such as signalling protocols, by reducing memory system penalties. Detailed measurements show that for TCP, most memory system costs are due to poor locality in the protocol code itself, rather than movement of data. We present a new technique, analogous to blocked matrix multiplication, for scheduling layer processing to reduce memory system costs, and analyze its performance in a synthetic environment.
Inhibition of airway remodeling in IL-5–deficient mice (2004)

To determine the role of IL-5 in airway remodeling, IL-5-deficient and WT mice were sensitized to OVA and challenged by repetitive administration of OVA for 3 months. IL-5-deficient mice had significantly less peribronchial fibrosis (total lung collagen content, peribronchial collagens III and V) and significantly less peribronchial smooth muscle (thickness of peribronchial smooth muscle layer, alpha-smooth muscle actin immunostaining) compared with WT mice challenged with OVA. WT mice had a significant increase in the number of peribronchial cells staining positive for major basic protein and TGF-beta. In contrast, IL-5-deficient mice had a significant reduction in the number of peribronchial cells staining positive for major basic protein, which was paralleled by a similar reduction in the number of cells staining positive for TGF-beta, suggesting that eosinophils are a significant source of TGF-beta in the remodeled airway. OVA challenge induced significantly higher levels of airway epithelial alphaVbeta6 integrin expression, as well as significantly higher levels of bioactive lung TGF-beta in WT compared with IL-5-deficient mice. Increased airway epithelial expression of alphaVbeta6 integrin may contribute to the increased activation of latent TGF-beta. These results suggest an important role for IL-5, eosinophils, alphaVbeta6, and TGF-beta in airway remodeling.
Market Liquidity and Trading Activity (2001)

ABSTRACT Previous studies of liquidity span short time periods and focus on the individual security. In contrast, we study aggregate market spreads, depths, and trading activity for U.S. equities over an extended time sample. Daily changes in market averages of liquidity and trading activity are highly volatile and negatively serially dependent. Liquidity plummets significantly in down markets. Recent market volatility induces a decrease in trading activity and spreads. There are strong day‐of‐the‐week effects; Fridays accompany a significant decrease in trading activity and liquidity, while Tuesdays display the opposite pattern. Long‐ and short‐term interest rates influence liquidity. Depth and trading activity increase just prior to major macroeconomic announcements.
Intermolecular Oxidative Annulation of 2‐Aminoanthracenes to Diazaacenes and Aza[7]helicenes (2012)

Which way to go: The product distribution in the efficient oxidation of 2-aminoanthracene derivatives to pyrazine- and pyrrole-fused bisanthracenes can be controlled by additives (see scheme; TFA=trifluoroacetic acid, DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone). The pyrrole-fused dimer can be regarded as an aza[7]helicene with a stable helical conformation. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
9.4 A 2×2 WLAN and Bluetooth combo SoC in 28nm CMOS with on-chip WLAN digital power amplifier, integrated 2G/BT SP3T switch and BT pulling cancelation (2016)

The 2×2 wireless LAN (WLAN) + Bluetooth (BT) combo chip continues to be the most versatile product category in the wireless connectivity space. It finds usage in a wide range of applications, such as laptops, tablets, high-end smartphones, gaming consoles, set-top boxes, wireless routers and in-car/personal hot-spot devices. Digital-intensive SoCs have been relying on Moore's law to keep the cost down. However, traditional RF and analog circuits are facing more difficulties to keep up with Moore's law due to the physical constraint of inductors, capacitors, and resistors. To overcome these difficulties, we leveraged digital and mixed-signal techniques to architect the transceiver, with a WLAN Digital PA (DPA), a WLAN All-Digital PLL (ADPLL), a BT ADPLL with pulling cancellation, and a high-speed SAR-ADC with reduced analog filter order in the WLAN RX.
A novel broadcast scheduling strategy using factor graphs and sum-product algorithm (2005)

This paper presents a novel self-organizing distributed algorithm for finding a broadcasting schedule in a packet radio network via only local collaborative interactions among neighboring network stations. Inspired by the huge success of the low density parity check (LDPC) codes in the field of error control coding, we transform the broadcast scheduling problem (BSP) into an LDPC-like problem through a factor graph. In the proposed algorithm, the constraint rules of the BSP are divided into many simple local rules, each of which is enforced by a local processing unit in the factor graph. The soft-information, describing the probability that each station will transmit a data packet, is then efficiently exchanged among the local processing units by using the sum-product algorithm to iteratively optimize the broadcasting schedule. Simulation results indicate that the proposed algorithm performs better than the other existing central-processing algorithms in terms of the channel utilization and the average packet delay. This is true especially when the network scenario is very complex. Furthermore, the proposed algorithm is both low in complexity and completely distributed, which makes it suitable for implementation in practical network applications.
Nonbone Marrow-Derived Circulating Progenitor Cells Contribute to Postnatal Neovascularization Following Tissue Ischemia (2007)

Circulating progenitor cells home to sites of postnatal neovascularization and differentiate into endothelial cells but questions remain regarding the source of these cells. Indeed, a recent study suggests that nonbone marrow-derived cells may be even more important than bone marrow-derived cells in the setting of transplant arteriosclerosis. Thus, we aimed to thoroughly investigate the contribution of nonbone marrow-derived progenitor cells for neovascularization. We exclusively identified nonbone marrow-derived progenitor cells by combining a parabiosis model with reverse bone marrow transplantation followed by hindlimb ischemia. In this model, nonbone marrow-derived circulating progenitor cells attributed for 74+/-13% of the circulating progenitor cells that incorporated into the ischemic hindlimb. Increasing evidence suggests that organs such as small intestine and liver contain a considerable number of tissue resident progenitor cells and, thus, represent putative sources for nonbone marrow-derived progenitors. To track organ-derived progenitors, we transplanted sex-mismatched small intestine or liver, respectively, into rats followed by induction of hindlimb ischemia. These experiments show that organ-derived progenitor cells are contributing to postnatal vasculogenesis (intestine: 4.7+/-3.7%; liver: 6.3+/-2.2%). Based on the subsequent observation that liver-derived nonhematopoietic c-kit(+)CD45(-) progenitors are mobilized on induction of hindlimb ischemia, we prospectively isolated and intravenously infused these progenitors from murine livers. The isolated cells demonstrated a marked capacity for enhancing neovascularization and restoring blood flow to the ischemic hindlimb (no cells: 26.4+/-4.8% of normal blood flow; c-kit(+)CD45(-) cells: 67.0+/-8.0% of normal flow; P<0.01). In conclusion, we find that nonbone marrow-derived c-kit(+)CD45(-) progenitors contribute to postnatal neovascularization to an extent that is similar to that of bone marrow-derived progenitor cells. Intestine and liver represent a rich source for mobilized tissue-residing progenitor cells.
Nanoparticles and Cell Longevity (2005)

The field of engineering has made substantial strides in nanotechnology, in the realm of materials science and construction of nanoscale devices. Nanomedicine encompasses application of cutting edge engineered nanostructures to biological systems and development of novel strategies for disease intervention. In the current review, we discuss the pharmacological application of nanoparticles as free radical scavengers and the capacity of nanoparticles to promote cell and organismal longevity.
O-Fucosylation of an antibody light chain: Characterization of a modification occurring on an IgG1 molecule (2008)

We describe the characterization of an O-fucosyl modification to a serine residue on the light chain of a recombinant, human IgG1 molecule expressed in Chinese hamster ovary (CHO) cells. Cation exchange chromatography (CEX) and hydrophobic interaction chromatography (HIC) were used to isolate a Fab population which was 146 Da heavier than the expected mass. Isolated Fab fragments were treated with a reducing agent to facilitate mass spectrometric analysis of the reduced light chain (LC) and fragment difficult (Fd). An antibody light chain with a net addition of 146 Da was detected by mass spectrometric analysis of the modified Fab. A light chain tryptic peptide in complementarity determining region-1 (CDR-1) was subsequently identified with a net addition of 146 Da by a peptide map. Results from a nanospray infusion of the modified peptide into a linear ion trap mass spectrometer with electron transfer dissociation (ETD) functionality indicated that the modified residue was a serine at position 30 in the light chain. Acid hydrolysis of the modified tryptic peptide followed by fluorescent labeling with 2-aminoanthranilic acid (2AA) and HPLC comparison with monosaccharide standards confirmed the presence of fucose on the light chain peptide. The presence of O-fucose on an antibody has not been previously reported. Currently, O-fucose has been described as occurring on mammalian proteins with amino acid sequence motifs associated with epidermal growth factor (EGF)-like repeats or thrombospondin type 1 repeats (TSRs). The amino acid sequence around the modified Ser in the IgG1 molecule does not conform to any known O-fucosylation sequence motif and thus is the first description of this type of modification on a nonconsensus sequence in a mammalian protein.
Differential response of prostate specific antigen to testosterone surge after luteinizing hormone‐releasing hormone analogue in prostate cancer and benign prostatic hyperplasia (2000)

There was a marked difference in the PSA response of patients with benign or malignant disease to the testosterone surge produced by the LHRH analogue. Although a larger study would be needed before LHRH-induced provocation could be proposed as a clinical test, in this small series the response was better than that for total PSA or f/tPSA in differentiating benign and malignant disease.
Comparison of a Multiplex Flow Cytometric Assay with Enzyme-Linked Immunosorbent Assay for Quantitation of Antibodies to Tetanus, Diphtheria, and Haemophilus influenzae Type b (2002)

We developed a multiplexed indirect immunofluorescence assay for antibodies to Haemophilus influenza type b (Hib) polysaccharide and the toxoids of Clostridium tetani (Tet) and Corynebacterium diphtheriae (Dip) based on the Luminex multiple-analyte profiling system. A pooled serum standard was calibrated against World Health Organization standards for Dip and Tet and an international standard for Hib. The multiplexed Luminex assay was compared to individual enzyme-linked immunosorbent assays (ELISAs) for the same analytes. By both methods, 75 (92.6%) of 81 of random serum samples had protective levels of antibody to Tet (> or = 0.1 IU/ml). For Dip, 81.5% of the samples had protective antibody levels (> or = 0.1 IU/ml) by ELISA and 80.2% had protective antibody levels by Luminex. Protective levels (> or = 1.0 microg/ml) of antibody to Hib were found in 45.0% of the samples tested by ELISA and in 39.0% of the samples tested by Luminex. The correlations (R(2)) between ELISA and Luminex of the 81 samples were 0.96, 0.96, and 0.91 for Tet, Dip, and Hib, respectively. There was also similar agreement between Luminex and ELISA for sera collected before and 1 month after Tet, Dip, and Hib vaccine administration. Both methods detected strong postvaccination responses. The Luminex method is an attractive alternative to ELISA since it reduces labor and reagent costs, as well as assay time.