gebhart/patrepeval huggingface dataset:
Prevention of experimental antiphospholipid syndrome and endothelial cell activation by synthetic peptides (1999)

Antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, repeated thromboembolic phenomena, and thrombocytopenia. The syndrome is believed to be caused by antiphospholipid beta-2-glycoprotein-I (beta2GPI)-dependent Abs or anti-beta2GPI Abs by themselves. Using a hexapeptide phage display library, we identified three hexapeptides that react specifically with the anti-beta2GPI mAbs ILA-1, ILA-3, and H-3, which cause endothelial cell activation and induce experimental APS. To enhance the binding of the peptides to the corresponding mAbs, the peptides were lengthened to correspond with the site of the beta2GPI epitope being recognized by these mAbs. As a result, the following three peptides were prepared: A, NTLKTPRVGGC, which binds to ILA-1 mAb; B, KDKATFGCHDGC, which binds to ILA-3 mAb; and C, CATLRVYKGG, which binds to H-3 mAb. Peptides A, B, and C specifically inhibit both in vitro and in vivo the biological functions of the corresponding anti-beta2GPI mAbs. Exposure of endothelial cells to anti-beta2GPI mAbs and their corresponding peptides led to the inhibition of endothelial cell activation, as shown by decreased expression of adhesion molecules (E-selectin, ICAM-1, VCAM-1) and monocyte adhesion. In vivo infusion of each of the anti-beta2GPI mAbs into BALB/c mice, followed by administration of the corresponding specific peptides, prevented the peptide-treated mice from developing experimental APS. The use of synthetic peptides that focus on neutralization of pathogenic anti-beta2GPI Abs represents a possible new therapeutic approach to APS.
Targeting the r(CGG) Repeats That Cause FXTAS with Modularly Assembled Small Molecules and Oligonucleotides (2014)

We designed small molecules that bind the structure of the RNA that causes fragile X-associated tremor ataxia syndrome (FXTAS), an incurable neuromuscular disease. FXTAS is caused by an expanded r(CGG) repeat (r(CGG)(exp)) that inactivates a protein regulator of alternative pre-mRNA splicing. Our designed compounds modulate r(CGG)(exp) toxicity in cellular models of FXTAS, and pull-down experiments confirm that they bind r(CGG)(exp) in vivo. Importantly, compound binding does not affect translation of the downstream open reading frame (ORF). We compared molecular recognition properties of our optimal compound to oligonucleotides. Studies show that r(CGG)(exp)'s self-structure is a significant energetic barrier for oligonucleotide binding. A fully modified 2'-OMethyl phosphorothioate is incapable of completely reversing an FXTAS-associated splicing defect and inhibits translation of the downstream ORF, which could have deleterious effects. Taken together, these studies suggest that a small molecule that recognizes structure may be more well suited for targeting highly structured RNAs that require strand invasion by a complementary oligonucleotide.
Regulation of metabolism and growth during immune challenge: an overview of cytokine function. (1997)

Commercially reared food animals encounter serial pathogenic and nonpathogenic immune challenges throughout production. Because of the diversion of nutrients away from growth in support of immune-related processes, immune challenge is considered a major obstacle to animals' achieving their genetic potential for growth or efficiency of gain. Scientists now recognize that many metabolic processes respond directly or indirectly to proinflammatory cytokines. This cytokine-mediated "reprogramming" of metabolism is a homeorhetic mechanism that ensures an adequate supply of nutrients for proliferation of lymphocyte and macrophage populations, antibody production, and hepatic synthesis of acute phase proteins. Proinflammatory cytokines have been linked to altered nutrient uptake and utilization. Anabolic processes are interrupted, and companion catabolic activities are amplified. Furthermore, cytokines may influence prenatal growth and development, and to the extent that postnatal proliferation and differentiation of myogenic and adipogenic cells contribute to postnatal growth, cytokine regulation of these events may ultimately influence growth. The following discussion is an overview of the impact of immune challenge and proinflammatory cytokines on metabolism and growth.
Morphological features of TMPRSS2–ERG gene fusion prostate cancer (2007)

The TMPRSS2-ETS fusion prostate cancers comprise 50-70% of the prostate-specific antigen (PSA)-screened hospital-based prostate cancers examined to date, making it perhaps the most common genetic rearrangement in human cancer. The most common variant involves androgen-regulated TMPRSS2 and ERG, both located on chromosome 21. Emerging data from our group and others suggests that TMPRSS2-ERG fusion prostate cancer is associated with higher tumour stage and prostate cancer-specific death. The goal of this study was to determine if this common somatic alteration is associated with a morphological phenotype. We assessed 253 prostate cancer cases for TMPRSS2-ERG fusion status using an ERG break-apart FISH assay. Blinded to gene fusion status, two reviewers assessed each tumour for presence or absence of eight morphological features. Statistical analysis was performed to look for significant associations between morphological features and TMPRSS2-ERG fusion status. Five morphological features were associated with TMPRSS2-ERG fusion prostate cancer: blue-tinged mucin, cribriform growth pattern, macronucleoli, intraductal tumour spread, and signet-ring cell features, all with p-values < 0.05. Only 24% (n=30/125) of tumours without any of these features displayed the TMPRSS2-ERG fusion. By comparison, 55% (n=38/69) of cases with one feature (RR=3.88), 86% (n=38/44) of cases with two features (RR=20.06), and 93% (n=14/15) of cases with three or more features (RR=44.33) were fusion positive (p<0.001). To our knowledge, this is the first study that demonstrates a significant link between a molecular alteration in prostate cancer and distinct phenotypic features. The strength of these findings is similar to microsatellite unstable colon cancer and breast cancer involving BRCA1 and BRCA2 mutations. The biological effect of TMPRSS2-ERG overexpression may drive pathways that favour these common morphological features that pathologists observe daily. These features may also be helpful in diagnosing TMPRSS2-ERG fusion prostate cancer, which may have both prognostic and therapeutic implications.
Mechanisms of dominant negative G‐protein α subunits (2007)

G-protein-coupled receptors (GPCRs) represent the largest class of membrane proteins and are the targets of 25-50% of drugs currently on the market. Dominant negative mutant Galpha subunits of heterotrimeric G-proteins have been extensively utilized to delineate G-protein signaling pathways and represent a promising new tool to study GPCR-dependent signaling in the CNS. There are different regions in various types of Galpha subunits in which mutations can give rise to a dominant negative phenotype. Such a mutant Galpha would compete with wild-type Galpha for binding to other proteins involved in the G-protein cycle and either block or reduce the response caused by wild-type Galpha. To date, there are three different mechanisms described for dominant negative Galpha subunits: sequestration of the Gbetagamma subunits, sequestration of the activated GPCR by the heterotrimeric complex, and sequestration of the activated GPCR by nucleotide-free Galpha. This review focuses on the development of dominant negative Galpha subunits, the different mechanisms used by various mutant Galpha subunits, and potential structural changes underlying the dominant negative effects.
Herpes Simplex Virus Type 1 DNA in Cerebrospinal Fluid of a Patient with Mollaret's Meningitis (1991)

MOLLARET'S meningitis is a rare disease characterized by recurrent, self-limited episodes of aseptic meningitis.1 Signs and symptoms of meningeal irritation appear acutely, in association with fever and pleocytosis of mononuclear cells. These episodes last two to five days or occasionally longer and remit spontaneously.2–6 Five to 15 attacks may occur, separated by symptom-free intervals of weeks to months. Transient neurologic abnormalities may be present during the attacks, but they disappear after the acute illness. The diagnosis of Mollaret's meningitis is made only after other recognized causes of recurrent lymphocytic meningitis have been excluded.2 Numerous attempts to establish a microbiologic cause . . .
PD-L1 Binds to B7-1 Only In Cis on the Same Cell Surface (2018)

Programmed death ligand 1 (PD-L1)-mediated immunosuppression regulates peripheral tolerance and is often co-opted by tumors to evade immune attack. PD-L1 binds to PD-1 but also binds to B7-1 (CD80) to regulate T-cell function. The binding interaction of PD-L1 with B7-1 and its functional role need further investigation to understand differences between PD-1 and PD-L1 tumor immunotherapy. We examined the molecular orientation of PD-L1 binding to B7-1 using cell-to-cell binding assays, ELISA, and flow cytometry. As expected, PD-L1-transfected cells bound to PD-1-transfected cells, and B7-1 cells bound to CD28 or CTLA-4-transfected cells; however, PD-L1 cells did not bind to B7-1 cells. By ELISA and flow cytometry with purified proteins, we found PD-L1 and B7-1 had a strong binding interaction only when PD-L1 was flexible. Soluble PD-1 and B7-1 competed for binding to PD-L1. Binding of native PD-L1 and B7-1 <i>in cis</i> on the same cell surface was demonstrated with NanoBiT proximity assays. Thus, PD-L1-B7-1 interaction can occur <i>in cis</i> on the same cell but not <i>in trans</i> between two cells, which suggests a model in which PD-L1 can bend via its 11-amino acid, flexible stalk to bind to B7-1 <i>in cis</i>, in a manner that can competitively block the binding of PD-L1 to PD-1 or of B7-1 to CD28. This binding orientation emphasizes the functional importance of coexpression of PD-L1 and B7-1 on the same cell. We found such coexpression on tumor-infiltrating myeloid cells. Our findings may help better utilize these pathways in cancer immunotherapy. <i>Cancer Immunol Res; 6(8); 921-9. ©2018 AACR</i>.
StreamObjects : dynamically-segmented scalable media over the Internet (1996)

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1996.
On Bandwidth Variation in Kernel Estimates-A Square Root Law (1982)

We consider kernel estimation of a smooth density $f$ at a point, but depart from the usual approach in admitting an adaptive dependence of the sharpness of the kernels on the underlying density. Proportionally varying the bandwidths like $f^{-1/2}$ at the contributing readings lowers the bias to a vanishing fraction of the usual value, and makes for performance seen in well-known estimators that force moment conditions on the kernel (and so sacrifice positivity of the curve estimate). Issues of equivariance and variance stabilitization are treated.
THE VIRUS WATCH PROGRAM: A CONTINUING SURVEILLANCE OF VIRAL INFECTIONS IN METROPOLITAN NEW YORK FAMILIES (1969)

During 10,577 person-months of surveillance over a four year period 142 coxsackie and 76 echovirus infections were detected by virus isolation. Serology revealed 73 additional infections, 65 with coxsackie and 8 with echoviruses. Because of the large number of sero-types encountered (types A9 and Bl–5 coxsackieviruses, types 2, 3, 6, 9, 11, 12, 14, 15, 17, 18, 20, 25, and 26 echoviruses plus reovirus type 1), generalization of the findings must be confined to the two major virus groups. Overall, entero-virus infection was a relatively rare occurrence. Fecal excretion predominated but respiratory excretion also occurred, especially of coxsackieviruses. Excretion of relatively long duration (up to 70 days) was not uncommon for coxsackie but infrequent for echoviruses. Based on intra-household spread, infectivity of cox-sackieviruses was fairly high (76% of exposed susceptible! and 25% of immunes); for echoviruses, apparent infectivity was substantially lower (43% of susceptibles and a single immune). At least 49% of coxsackie and 55% of echo-virus infections were subclinical. Allowance for illness “expected” in the absence of the observed infections yielded attributable illness rates of 24 or 19% for coxsackie and 9.4 or 18.5% for echovirus infections (depending on whether “virus-fre” or “self” controls were used in the correction). The true rates are believed to be somewhat higher. All of the associated illness was mild (respiratory disease alone or accompanied by enteric disease, rash or other manifestation). This suggests that the more severe manifestations attributed to these agents are relatively rare or that the viral strains invading the VW families were of low virulence.
Semantic issues in integrating data from different models to achieve data interoperability. (2007)

Matching clinical data to codes in controlled terminologies is the first step towards achieving standardisation of data for safe and accurate data interoperability. The MoST automated system was used to generate a list of candidate SNOMED CT code mappings. The paper discusses the semantic issues which arose when generating lexical and semantic matches of terms from the archetype model to relevant SNOMED codes. It also discusses some of the solutions that were developed to address the issues. The aim of the paper is to highlight the need to be flexible when integrating data from two separate models. However, the paper also stresses that the context and semantics of the data in either model should be taken into consideration at all times to increase the chances of true positives and reduce the occurrence of false negatives.
Singel-Polarisation Operation of Injection Locked Fibre DFB Lasers (2005)

We report that fibre DFB lasers could successfully operate in a single polarisation, either by injection locking with an external singlepolarisation light, or by self-injection locking with a polarisation-selective optical feedback
Polarity analysis of texts using discourse structure (2011)

Sentiment analysis has applications in many areas and the exploration of its potential has only just begun. We propose Pathos, a framework which performs document sentiment analysis (partly) based on a document's discourse structure. We hypothesize that by splitting a text into important and less important text spans, and by subsequently making use of this information by weighting the sentiment conveyed by distinct text spans in accordance with their importance, we can improve the performance of a sentiment classifier. A document's discourse structure is obtained by applying Rhetorical Structure Theory on sentence level. When controlling for each considered method's structural bias towards positive classifications, weights optimized by a genetic algorithm yield an improvement in sentiment classification accuracy and macro-level F1 score on documents of 4.5% and 4.7%, respectively, in comparison to a baseline not taking into account discourse structure.
Identification of new NIK inhibitors by discriminatory analysis‐based molecular docking and biological evaluation (2019)

NF-κB inducing kinase (NIK) is a key regulator in the noncanonical nuclear factor κB cells (NF-κB) signaling pathway. Dysregulation of NIK is often related with autoimmune disorders and malignancies. However, the number of reported NIK inhibitors is scarce. Discriminatory analysis-based molecular docking was used to examine the accuracy of the binding conformation and to estimate the binding affinity, leading to the identiﬁcation of several new NIK inhibitors with moderate IC<sub>50</sub> (ranging from 48.9 to 103.4 μM). Among them, compound 5, the most potent one (IC<sub>50</sub> 48.9 ± 6.9 μM), also showed moderate antiproliferation activity against cancer SW1990 cells, with an IC<sub>50</sub> value of 20.1 ± 6.0 μM. Further dynamic simulations were performed to provide more in-depth details on the binding conformation of compound 5 and the NIK protein, providing some structural clues for further optimization of compound 5 as a novel NIK inhibitor.
Stimulation of gene expression by introns: conversion of an inhibitory intron to a stimulatory intron by alteration of the splice donor sequence (1993)

Efficient expression of many mammalian genes depends on the presence of at least one intron. We previously showed that addition of almost any of the introns from the mouse thymidylate synthase (TS) gene to an intronless TS minigene led to a large increase in expression. However, addition of intron 4 led to a reduction in minigene expression. The goal of the present study was to determine why TS intron 4 was unable to stimulate expression. Insertion of intron 4 into an intron-dependent derivative of the ribosomal protein L32 gene did not lead to a significant increase in expression, suggesting that its inability to stimulate expression was due to sequences within the intron. Deleting most of the interior of intron 4, improving the putative branch point, removing purines from the pyrimidine stretch at the 3' end of the intron, or removing possible alternative splice acceptor or donor sites within the intron each had little effect on the level of expression. However, when the splice donor sequence of intron 4 was modified so that it was perfectly complementary to U1 snRNA, the modified intron 4 stimulated expression approximately 6-fold. When the splice donor site of TS intron 1 (a stimulatory intron) was changed to that of TS intron 4, the modified intron 1 was spliced very inefficiently and lost the ability to stimulate mRNA production. Our observations support the idea that introns can stimulate gene expression by a process that depends directly on the splicing reaction.
Identification of isoform‐specific T‐cell epitopes in the major timothy grass pollen allergen, Phl p 5 (1999)

The T-cell reactivity of the three grass-allergic patients investigated shows that isoallergen-specific T-cell epitopes are found throughout the peptide backbone of Phl p 5a and Phl p 5b, and dominant T-cell epitopes of Phl p 5 were not identified. This indicates that a mixture of at least full-length rPhl p 5a and rPhl p 5b may be required to target the total Phl p 5-specific T-cell response of atopic patients.
Specific Integrin Labeling in Living Cells Using Functionalized Nanocrystals (2007)

We present an integrin labeling method using functionalized quantum dots (QDs). Cyclic Arg-Gly-Asp (RGD) peptides and a biotin-streptavidin linkage are used to specifically couple individual QDs to integrins of living cells. The spacer distance between the RGD sequence and the QD surface is a crucial parameter to ensure specific binding to individual alpha(v)beta(3) integrins of osteoblast cells. Despite blinking, the position of single QDs is tracked with nanometer precision and localized diffusive behavior is observed. We show that blinking events do not prevent the acquisition of quantitative parameters from the QD trajectories.
Protective Effect of Carbon Monoxide–Releasing Compounds in Ischemia-Induced Acute Renal Failure (2005)

Heme oxygenase (HO) induction has been demonstrated to be beneficial in limiting the extent of cellular damage after ischemia-induced acute renal failure (ARF). Because increased HO activity is associated with the production of carbon monoxide (CO) as well as the potent antioxidant bilirubin, it is unclear which of the two is of greater importance in the protective effects of HO induction. The purpose of this study was to determine the protective role of CO alone in ischemia-induced ARF. Bilateral clamping of the renal pedicle for 40 min was associated with a ninefold increase in the levels of plasma creatinine 24 h after reperfusion as compared with normal plasma creatinine levels; however, administration of CO donor compounds tricarbonyldichlororuthenium(II) dimer, ([Ru(CO)(3)Cl(2)](2), 10 mg/kg) or tricarbonylchloro(glycinato)ruthenium(II) ([Ru(CO)(3)Cl(glycinate)], (CORM-3) 1 h before the onset of ischemia significantly decreased the levels of plasma creatinine 24 h after reperfusion as compared with vehicle-treated mice. Surprising, treatment with the CO donors was associated with an increase in HO activity 24 h after ischemia. For determining whether the protective effects of the CO donors were due to CO or HO-1 induction, experiments were performed in which HO was inhibited before administration of the CO donors. Pretreatment with the HO inhibitor had no effect on the level of plasma creatinine 24 h after reperfusion after treatment with the CO donor compounds. These results suggest that CO itself may be protective and limit renal damage in ischemia induced ARF.
Phi DM-Dialog: an experimental speech-to-speech dialog translation system (1991)

Phi DM-Dialog, one of the first experimental speech-to-speech systems and the first to demonstrate simultaneous interpretation possibilities, is described. An overview is given of the model behind Phi DM-Dialog. It consists of a memory network for representing various knowledge levels and markers for inferencing. The markers have rich information content. The integration of speech and natural language processing in Phi DM-Dialog and its cost-based scheme of ambiguity resolution are discussed. Its simultaneous interpretation capability, which is made possible by an incremental parsing and generation algorithm, is examined. Prototype system results are reported.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Chemistry of Chloroformates (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Chemistry of ChloroformatesMarkus Matzner, Raymond P. Kurkjy, and Robert J. CotterCite this: Chem. Rev. 1964, 64, 6, 645–687Publication Date (Print):December 1, 1964Publication History Published online1 May 2002Published inissue 1 December 1964https://pubs.acs.org/doi/10.1021/cr60232a004https://doi.org/10.1021/cr60232a004research-articleACS PublicationsRequest reuse permissionsArticle Views2284Altmetric-Citations121LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts