gebhart/patrepeval huggingface dataset:
Complex Protein Interactions within the Human Polyadenylation Machinery Identify a Novel Component (2000)

Polyadenylation of mRNA precursors is a two-step reaction requiring multiple protein factors. Cleavage stimulation factor (CstF) is a heterotrimer necessary for the first step, endonucleolytic cleavage, and it plays an important role in determining the efficiency of polyadenylation. Although a considerable amount is known about the RNA binding properties of CstF, the protein-protein interactions required for its assembly and function are poorly understood. We therefore first identified regions of the CstF subunits, CstF-77, CstF-64, and CstF-50, required for interaction with each other. Unexpectedly, small regions of two of the subunits participate in multiple interactions. In CstF-77, a proline-rich domain is necessary not only for binding both other subunits but also for self-association, an interaction consistent with genetic studies in Drosophila. In CstF-64, a small region, highly conserved in metazoa, is responsible for interactions with two proteins, CstF-77 and symplekin, a nuclear protein of previously unknown function. Intriguingly, symplekin has significant similarity to a yeast protein, PTA1, that is a component of the yeast polyadenylation machinery. We show that multiple factors, including CstF, cleavage-polyadenylation specificity factor, and symplekin, can be isolated from cells as part of a large complex. These and other data suggest that symplekin may function in assembly of the polyadenylation machinery.
EpiJen: a server for multistep T cell epitope prediction (2006)

EpiJen is a reliable multi-step algorithm for T cell epitope prediction, which belongs to the next generation of in silico T cell epitope identification methods. These methods aim to reduce subsequent experimental work by improving the success rate of epitope prediction.
Exogenous Natural Surfactant for Treatment of Acute Lung Injury and the Acute Respiratory Distress Syndrome (2009)

In this study, instillation of a large bolus of exogenous natural porcine surfactant HL 10 into patients with acute lung injury and ARDS did not improve outcome and showed a trend toward increased mortality and adverse effects. Clinical trial registered with www.clinicaltrials.gov (NCT 00742482).
A Quantitative Assessment of Group Delay Methods for Identifying Glottal Closures in Voiced Speech (2006)

Measures based on the group delay of the LPC residual have been used by a number of authors to identify the time instants of glottal closure in voiced speech. In this paper, we discuss the theoretical properties of three such measures and we also present a new measure having useful properties. We give a quantitative assessment of each measure's ability to detect glottal closure instants evaluated using a speech database that includes a direct measurement of glottal activity from a Laryngograph/EGG signal. We find that when using a fixed-length analysis window, the best measures can detect the instant of glottal closure in 97% of larynx cycles with a standard deviation of 0.6 ms and that in 9% of these cycles an additional excitation instant is found that normally corresponds to glottal opening. We show that some improvement in detection rate may be obtained if the analysis window length is adapted to the speech pitch. If the measures are applied to the preemphasized speech instead of to the LPC residual, we find that the timing accuracy worsens but the detection rate improves slightly. We assess the computational cost of evaluating the measures and we present new recursive algorithms that give a substantial reduction in computation in all cases.
Levetiracetam in social phobia: a placebo controlled pilot study (2005)

While serotonergic antidepressants are now established as first-line pharamcotherapy for generalized social anxiety disorder (SAD), other agents with different mechanisms have shown promise in treating SAD. The aim of this pilot study is to examine the efficacy and safety of levetiracetam (LEV), an anticonvulsant with calcium channel modulating properties, in treating SAD. Adult outpatients meeting DSM-IV criteria for SAD were randomly assigned (2:1) to double-blind treatment with either LEV (500-3000 mg/day) or placebo (PBO) for 7 weeks. The primary outcome measures were the change from baseline in the Brief Social Phobia Scale (BSPS) and response using the Clinical Global Impression of Improvement scale (CGI-I). The mean (SD) BSPS scores at baseline and endpoint were 45.4 (9.7) and 31.2 (19.7) for LEV (n=9), compared to 43.5 (8.4) and 37.8 (19.9) for PBO (n =7) (ITT; ns). Rates of response were 22% for LEV and 14% for PBO using the CGI-I. Using a BSPS response criterion (>30% reduction), response rates were 44% for LEV and 14% for PBO. The effect sizes of LEV relative to PBO were 0.33 for the BSPS and 0.50 for the LSAS. In summary, the results of this study, while negative on the pre-defined measures, suggest promise for LEV as a new treatment of SAD. Further work should be carried out with larger sample sizes and optimal dosing strategies of the drug.
Application of anti-sialyl Lea monoclonal antibody, KM231, for immunotherapy of cancer. (1992)

A mouse monoclonal antibody (MoAb), KM231 raised against human gastric cancer was found to recognize sialyl Lea -epitope expressed on glycoprotein and glycolipid with high affinity. KM231 reacted with many human gastrointestinal cancer tissues and could detect the antigen shed in sera of cancer patients. The present study was designed to evaluate competence of KM231 for immunotherapy of cancer. We first confirmed that KM231 could probe the cancer cells in vivo by injecting biotinylated KM231 into nude mice bearing human colorectal carcinoma cell, SW1116. Light- and electron-microscopic examination showed that the MoAb was localized in the tumor tissues and bound to the plasma membrane and cytoplasmic endosomes. Imaging studies with 125I-labeled KM231 revealed specific localization of the antibody in SW1116 tumors transplanted into nude mice. From Scatchard analysis of KM231 binding, the number of KM231 molecules bound to per SW1116 cell was calculated approximately 1.9 x 10(6) and the association constant was 1.3 x 10(8) liter/mol. We made KM231-ricin A chain immunotoxin for evaluating the tumoricidal effect of KM231. The immunotoxin exerted strong cytotoxicity toward sialyl Lea-expressing tumor cells specifically in vitro, but not toward sialyl Lea non-expressing cells. The in vivo tumoricidal effect of the immunotoxin was examined on ascites and subcutaneous xenograft tumors in nude mice. Three intraperitoneal injections of the immunotoxin (1.6 x 10(-6) mol) into nude mice bearing SW1116 ascites tumor resulted in extension of survival by 204% compared with controls. Further, repeated intraperitoneal administration of the immunotoxin (1.4 - 2 x 10(-6) mol) significantly inhibited the growth of established subcutaneous tumor (ratio of tumor inhibition = 0.7 - 0.54). These results indicated that KM231 has the ability to probe sialyl Lea-expressing tumor cells in vivo with high efficiency and to become tumoricidal drug when it conjugated with cytotoxic reagents like ricin A chain.
Targeting TRAIL Agonistic Receptors for Cancer Therapy (2007)

Based on preclinical studies demonstrating that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exerts a potent and cancer cell-specific proapoptotic activity, recombinant TRAIL as well as agonistic anti-TRAIL-R1 and anti-TRAIL-R2 antibodies recently entered clinical trials. Additionally, gene therapy approaches using TRAIL-encoding adenovirus (Ad-TRAIL) are currently being developed to overcome the limitations inherent to TRAIL receptor targeting, i.e., pharmacokinetic of soluble TRAIL, pattern of receptor expression, and tumor cell resistance. To optimize gene therapy approaches, CD34+ cells transduced with Ad-TRAIL (CD34-TRAIL+) have been investigated as cellular vehicles for TRAIL delivery. Transduced cells exhibit a potent tumor killing activity on a variety of tumor cell types both in vitro and in vivo and are also cytotoxic against tumor cells resistant to soluble TRAIL. Studies in tumor-bearing nonobese diabetic/severe combined immunodeficient mice suggest that the antitumor effect of CD34-TRAIL+ cells is mediated by both direct tumor cell killing due to apoptosis and indirect tumor cell killing due to vascular-disrupting mechanisms. The clinical translation of cell and gene therapy approaches represent a challenging strategy that might achieve systemic tumor targeting and increased intratumor delivery of the therapeutic agent.
Classification of Stroke Subtypes (2009)

This article reviews published stroke subtype classification systems and offers rules and a basis for a new way to subtype stroke patients. Stroke subtyping can have different purposes, e.g. describing patients' characteristics in a clinical trial, grouping patients in an epidemiological study, careful phenotyping of patients in a genetic study, and classifying patients for therapeutic decision-making in daily practice. The classification should distinguish between ischemic and hemorrhagic stroke, subarachnoid hemorrhage, cerebral venous thrombosis, and spinal cord stroke. Regarding the 4 main categories of etiologies of ischemic stroke (i.e. atherothrombotic, small vessel disease, cardioembolic, and other causes), the classification should reflect the most likely etiology without neglecting the vascular conditions that are also found (e.g. evidence of small vessel disease in the presence of severe large vessel obstructions). Phenotypes of large cohorts can also be characterized by surrogate markers or intermediate phenotypes (e.g. presence of internal carotid artery plaque, intima-media thickness of the common carotid artery, leukoaraiosis, microbleeds, or multiple lacunae). Parallel classifications (i.e. surrogate markers) may serve as within-study abnormalities to support research findings.
Low temperature cycled PCR protocol for Klenow fragment of DNA polymerase I in the presence of proline (1999)

A method for performing cycled PCR at low temperatures, using the thermolabile Klenow fragment of DNA polymerase I, is reported. Application of proline as a buffer additive in the range of 3.0-5.5 M remarkably increases the thermal stability of the polymerase and decreases the denaturation temperature of DNAtemplate. This method might be applicable to a broad spectrum of thermolabile DNA polymerases in cycled PCR and other methods of DNA amplification.
Piperidine Derivatives. XXX. 1,4-Dialkyl-4-arylpiperidines (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPiperidine Derivatives. XXX. 1,4-Dialkyl-4-arylpiperidinesS. M. McElvain and David H. ClemensCite this: J. Am. Chem. Soc. 1958, 80, 15, 3915–3923Publication Date (Print):August 1, 1958Publication History Published online1 May 2002Published inissue 1 August 1958https://pubs.acs.org/doi/10.1021/ja01548a030https://doi.org/10.1021/ja01548a030research-articleACS PublicationsRequest reuse permissionsArticle Views483Altmetric-Citations55LEARN 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
Identification of the Major Site of Apolipoprotein B Modification by Advanced Glycosylation End Products Blocking Uptake by the Low Density Lipoprotein Receptor (1995)

Advanced glycosylation end products (AGEs) arise from glucose-derived Amadori products and have been implicated in the pathogenesis of diabetic vascular disease. We recently reported the presence of an AGE-modified form of low density lipoprotein (LDL) that circulates in high amounts in patients with diabetes or renal insufficiency and that exhibits impaired plasma clearance kinetics. We utilized AGE-specific antibodies to identify the major sites of AGE modification within protease-digested preparations of apolipoprotein B that impair the binding of the AGE-modified form of LDL by human fibroblast LDL receptors. The predominant site of AGE immunoreactivity was found to lie within a single, 67-amino acid region located 1791 residues NH2-terminal of the putative LDL receptor binding domain. These data point to the high reactivity and specificity of this site for AGE formation and provide further evidence for important structural interactions between the LDL receptor binding domain and remote regions of the apolipoprotein B polypeptide.
Role of the Mannose Receptor in the Immune Response (2001)

The mannose receptor (MR) recognizes a range of carbohydrates present on the surface and cell walls of micro-organisms. The MR is primarily expressed on macrophages and dendritic cells and is involved in MR-mediated endocytosis and phagocytosis. In addition, the MR plays a key role in host defense and provides a link between innate and adaptive immunity. Herein, we will review the role of the MR in innate host defense as well as the recent evidence for its role in the adaptive response, for both humoral and cellular immune responses.
Quercetin reduces cisplatin nephrotoxicity in rats without compromising its anti-tumour activity (2011)

Co-treatment with quercetin partially prevented all the renal effects of cisplatin, whereas it did not impair its anti-tumour activity. In conclusion, in a model of tumour-bearing rats, quercetin prevents the nephrotoxic effect of cisplatin without affecting its anti-tumour activity.
Potent Neuroprotective Properties against the Alzheimer β-Amyloid by an Endogenous Melatonin-related Indole Structure, Indole-3-propionic Acid (1999)

Widespread cerebral deposition of a 40-43-amino acid peptide called the amyloid beta-protein (Abeta) in the form of amyloid fibrils is one of the most prominent neuropathologic features of Alzheimer's disease. Numerous studies suggest that Abeta is toxic to neurons by free radical-mediated mechanisms. We have previously reported that melatonin prevents oxidative stress and death of neurons exposed to Abeta. In the process of screening indole compounds for neuroprotection against Abeta, potent neuroprotective properties were uncovered for an endogenous related species, indole-3-propionic acid (IPA). This compound has previously been identified in the plasma and cerebrospinal fluid of humans, but its functions are not known. IPA completely protected primary neurons and neuroblastoma cells against oxidative damage and death caused by exposure to Abeta, by inhibition of superoxide dismutase, or by treatment with hydrogen peroxide. In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals. In contrast with other antioxidants, IPA was not converted to reactive intermediates with pro-oxidant activity. These findings may have therapeutic applications in a broad range of clinical situations.
Apolipoprotein B localization in coronary atherosclerotic plaques from cynomolgus monkeys. (1983)

The presence of apolipoprotein B (apo B) was determined in atherosclerotic lesions of coronary arteries from cynomolgus monkeys placed on a hypercholesterolemic diet for one year. Immunofluorescence techniques were applied to sections of arteries that were fixed by perfusion with formalin and embedded in paraffin. Segments of right coronary, left anterior descending, and left circumflex arteries were observed. All segments demonstrated substantial intimal thickening, accompanied by areas of necrosis at the base of the plaque, usually located on the luminal side of the internal elastic lamina. Large clusters of foam cells could be found at the base of such plaques, between intimal smooth muscle cells in the fibromuscular cap, and frequently in the tunica media in regions of necrosis. Immunofluorescence depicting apo B was usually confined to the intima, especially in the necrotic core, but could also be seen in the media in regions in which the internal elastic lamina was missing. Apo B often filled the extracellular space between smooth muscle cells and groups of foam cells but was not identified in the cytoplasm of intact cells. Apo B-positive areas were usually also positive for alcian blue staining, suggesting LDL-sulfated glycosaminoglycan coexistence at such sites. The localization pattern of apo B in lesioned coronary arteries from cynomolgus monkeys was consistent with that found in human coronary lesions, suggesting that diet-induced hypercholesterolemia in such monkeys may be a valid model for studying the role of LDL in human atherogenesis.
Adjuvant Treatment With Neuroserpin Increases the Therapeutic Window for Tissue-Type Plasminogen Activator Administration in a Rat Model of Embolic Stroke (2002)

Administration of neuroserpin after stroke is neuroprotective, seemingly because it blocks the extravascular effect of tPA, leading to subsequent decrease in stroke volume and widening of the therapeutic window for the thrombolytic effect of tPA.
Ribonuclease H2 mutations induce a cGAS / STING ‐dependent innate immune response (2016)

Aicardi-Goutières syndrome (AGS) provides a monogenic model of nucleic acid-mediated inflammation relevant to the pathogenesis of systemic autoimmunity. Mutations that impair ribonuclease (RNase) H2 enzyme function are the most frequent cause of this autoinflammatory disorder of childhood and are also associated with systemic lupus erythematosus. Reduced processing of eitherRNA:DNAhybrid or genome-embedded ribonucleotide substrates is thought to lead to activation of a yet undefined nucleic acid-sensing pathway. Here, we establishRnaseh2b(A174T/A174T)knock-in mice as a subclinical model of disease, identifying significant interferon-stimulated gene (ISG) transcript upregulation that recapitulates theISGsignature seen inAGSpatients. The inflammatory response is dependent on the nucleic acid sensor cyclicGMP-AMPsynthase (cGAS) and its adaptorSTINGand is associated with reduced cellular ribonucleotide excision repair activity and increasedDNAdamage. This suggests thatcGAS/STINGis a key nucleic acid-sensing pathway relevant toAGS, providing additional insight into disease pathogenesis relevant to the development of therapeutics for this childhood-onset interferonopathy and adult systemic autoimmune disorders.
An Unusually Easy Oxidative Dequaternization of N-Alkyl-1,2,4-triazinium Salts (1995)

Unusually easy dequaternization has been found to occur on treatment of 1-alkyl-3-morpholino-5-phenyl-1,2,4-triazinium iodides with triethylamine in alcohol or acetone solutions at room temperature; a plausible reaction mechanism has been advanced on the basis of NMR and kinetic studies.
JIPs and RIPs: the regulation of plant gene expression by jasmonates in response to environmental cues and pathogens. (1994)

After its first description as a fragrant constituent of the es? sential oil of Jasminum grandiflorum (Demole et al., 1962), (-)-jasmonic acid methyl ester (methyl c/s-2-(2-penten-1-yl)3-oxocyclopentenyl acetate, also known as methyl jasmonate [MeJA]), and related compounds were found to be widespread in the plant kingdom (Meyer et al., 1984). In addition, jas? monates occur in fungi and algae (for references, see Sembdner and Parthier, 1993). Interestingly, MeJA js also a component of female-attracting pheromones in certain moths (Baker et al., 1991). (-)-Jasmonic acid [(-)-JA] and its derivatives are cyclopentanone compounds that are synthesized from linolenic acid by a sequence of as yet poorly characterized reactions (Vick and Zimmerman, 1984). The natural biosynthetic product of this pathway in most plant species appears to be (+)-7-/so-JA, which is rapidly converted into (-)-JA by isomerization. (-)-JA has been shown to undergo various modifications, giving rise to numerous metabolites with differing structures and biologi? cal activities. Major physiologically active compounds are (-)-JA, MeJA, and the amino acid conjugates of (-)-JA with isoleucine, valine, or leucine (for review, see Sembdner and Parthier, 1993). (-)-JA and MeJA (which will be collectively referred to throughout this review as jasmonates) affect plant growth and development in a pleiotropic manner (for reviews, see Parthier, 1990,1991; Staswick, 1992; Sembdner and Parthier, 1993). Re? cently, jasmonates have been proposed to be stress-related compounds (Farmer and Ryan, 1990; Parthier, 1990, 1991; Enyedi et al., 1992; Farmer et al., 1992; Gundlach et al., 1992; Muller et al., 1993). MeJA, in particular, is a signal molecule that is released in plants in response to various stresses, such as wounding or pathogen attack (Creelman et al., 1992),
Taxol: the first of the taxanes, an important new class of antitumor agents. (1992)

The taxanes represent the first class of antimicrotubule agents with a new mechanism of cytotoxic action since the introduction of the vinca alkaloids several decades ago. These compounds may prove to be the "anticancer drugs of the 1990s," just as the anthracyclines and the platinum compounds were the "anticancer drugs" of the 1970s and 1980s. Like the platinums, taxol, the prototypic taxane, has shown significant antineoplastic activity in patients with advanced ovarian cancer, with response rates ranging from 20% to 50%. Moreover, taxol has been shown to be useful in patients with platinum-resistant ovarian cancer. Although phase II screening is not yet complete, the results of phase II studies of taxol in advanced cancers of the ovary, breast (response rates, 56% to 62%), and lung (response rates, 21% to 24%) have rekindled interest in the microtubule as a prime strategic target for cancer therapy. After briefly reviewing the mechanisms of antineoplastic action and resistance and the results of preliminary clinical and pharmacological studies, this review will discuss several critical issues that will be addressed in future clinical trials, developmental directions, and drug supply. Although this review will focus primarily on taxol, the results of preliminary investigations with the semisynthetic taxane analog taxotere will also be discussed.
Transmembrane Rectified Electron Transfer through π-Conjugated Electroactive Langmuir–Blodgett Monolayers on Gold Electrodes (1994)

Abstract Novel amphiphiles with π-conjugated electroactive groups, 1-methyl-4-[2-[4-[2-(4-pyridyl)vinyl]phenyl]vinyl]pyridinium perchlorate (1), and 1-methyl-4-[2-[4-[2-(4-quinolyl)vinyl]phenyl]vinyl]quinolinium perchlorate (2), were designed and synthesized. Both compounds formed expanded monolayers at air–water interfaces. The monolayers transferred on gold disk electrodes at 25 mN m−1 by the Langmuir–Blodgett technique (horizontal lifting method) show one electron reduction/oxidation couple: Epa = −0.86 V, Epc = −1.08 V vs. SCE for 1/Au and Epa = −0.78 V, and Epc = −0.84 V vs. SCE for 2/Au. Rectified transmembrane electron transfer through the LB monolayers of 1 and 2 on gold electrodes to [Fe(CN)6]3− in aqueous solutions has been proved by cyclic voltammetry and potential-step chronocoulometry.