gebhart/patrepeval huggingface dataset:
Comparison of the Particle Sizes of Different Steroids and the Effect of Dilution (2007)

Commercial betamethasone is the recommended preparation if a nonsoluble steroid is preferred. Dexamethasone is a nonparticulate steroid, but its routine use awaits further studies on its safety and efficacy.
1,3-Dipolar cycloadditions of 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide to (phenylsulfonyl)allenes (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1,3-Dipolar cycloadditions of 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide to (phenylsulfonyl)allenesLuca Bruche, Maria Luisa Gelmi, and Gaetano ZecchiCite this: J. Org. Chem. 1985, 50, 17, 3206–3208Publication Date (Print):August 1, 1985Publication History Published online1 May 2002Published inissue 1 August 1985https://pubs.acs.org/doi/10.1021/jo00217a037https://doi.org/10.1021/jo00217a037research-articleACS PublicationsRequest reuse permissionsArticle Views167Altmetric-Citations25LEARN 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
Improved accuracy of supervised CRM discovery with interpolated Markov models and cross-species comparison (2011)

Despite recent advances in experimental approaches for identifying transcriptional cis-regulatory modules (CRMs, 'enhancers'), direct empirical discovery of CRMs for all genes in all cell types and environmental conditions is likely to remain an elusive goal. Effective methods for computational CRM discovery are thus a critically needed complement to empirical approaches. However, existing computational methods that search for clusters of putative binding sites are ineffective if the relevant TFs and/or their binding specificities are unknown. Here, we provide a significantly improved method for 'motif-blind' CRM discovery that does not depend on knowledge or accurate prediction of TF-binding motifs and is effective when limited knowledge of functional CRMs is available to 'supervise' the search. We propose a new statistical method, based on 'Interpolated Markov Models', for motif-blind, genome-wide CRM discovery. It captures the statistical profile of variable length words in known CRMs of a regulatory network and finds candidate CRMs that match this profile. The method also uses orthologs of the known CRMs from closely related genomes. We perform in silico evaluation of predicted CRMs by assessing whether their neighboring genes are enriched for the expected expression patterns. This assessment uses a novel statistical test that extends the widely used Hypergeometric test of gene set enrichment to account for variability in intergenic lengths. We find that the new CRM prediction method is superior to existing methods. Finally, we experimentally validate 12 new CRM predictions by examining their regulatory activity in vivo in Drosophila; 10 of the tested CRMs were found to be functional, while 6 of the top 7 predictions showed the expected activity patterns. We make our program available as downloadable source code, and as a plugin for a genome browser installed on our servers.
THE EFFECT OF ALTERNATIVE REGULATORY TREATMENT OF TAX DEPRECIATION ON UTILITY TAX PAYMENTS (1973)

A simulation model is utilized to generate representative time streams of income tax payments by typical regulated utilities under the flow through and normalization regulatory methods. A comparison of the present worth of such simulated tax payments over time under the alternative regulatory methods provides a means of determining the impact of each regulatory method on income tax payments by regulated utilities. These simulations indicate that the flow through regulatory method can frequently result in a higher present value of tax revenue. The normalization regulatory method generates more income taxes than flow through only in high, constant growth situations where the regulatory case for using normalization is weak.
WebWinnow (2014)

Organized cybercrime on the Internet is proliferating due to exploit kits. Attacks launched through these kits include drive-by-downloads, spam and denial-of-service. In this paper, we tackle the problem of detecting whether a given URL is hosted by an exploit kit. Through an extensive analysis of the workflows of about 40 different exploit kits, we develop an approach that uses machine learning to detect whether a given URL is hosting an exploit kit. Central to our approach is the design of distinguishing features that are drawn from the analysis of attack-centric and self-defense behaviors of exploit kits. This design is based on observations drawn from exploit kits that we installed in a laboratory setting as well as live exploit kits that were hosted on the Web. We discuss the design and implementation of a system called WEBWINNOW that is based on this approach. Extensive experiments with real world malicious URLs reveal that WEBWINNOW is highly effective in the detection of malicious URLs hosted by exploit kits with very low false-positives.
Circulating L-Selectin is Elevated in Patients with Plasmodium falclparum Malaria (1995)

Colleagues-The interactions between malaria-parasitized erythrocytes and host cells are highly cooperative and finely regulated processes that contribute to the evasion of host immune mechanisms as well as to the pathogenesis of the disease, in particular the development of complicated malaria [I]. Intercellular adhesion molecule-l , vascular cell adhesion molecule-l , CD36, thrombospondin, and E-selectin are endothelial counterreceptors for parasitized erythrocytes. Elevated serum concentrations of corresponding soluble forms have been demonstrated during acute malaria
Alloying element vaporization during laser spot welding of stainless steel. (2004)

Alloying element loss from the weld pool during laser spot welding of stainless steel was investigated experimentally and theoretically. The experimental work involved determination of work-piece weight loss and metal vapor composition for various welding conditions. The transient temperature and velocity fields in the weld pool were numerically simulated. The vaporization rates of the alloying elements were modeled using the computed temperature profiles. The fusion zone geometry could be predicted from the transient heat transfer and fluid flow model for various welding conditions. The laser power and the pulse duration were the most important variables in determining the transient temperature profiles. The velocity of the liquid metal in the weld pool increased with time during heating and convection played an increasingly important role in the heat transfer. The peak temperature and velocity increased significantly with laser power density and pulse duration. At very high power densities, the computed temperatures were higher than the boiling point of 304 stainless steel. As a result, evaporation of alloying elements was caused by both the total pressure and the concentration gradients. The calculations showed that the vaporization occurred mainly from a small region under the laser beam where the temperatures were very high. Themore » computed vapor loss was found to be lower than the measured mass loss because of the ejection of tiny metal droplets owing to the recoil force exerted by the metal vapours. The ejection of metal droplets has been predicted by computations and verified by experiments.« less
Capsaicin and its analogs induce ion channels in planar lipid bilayers (1995)

The irritating, pungent compound, capsaicin (10-20 microM), induces the formation of non-selective ion channels with a wide variety of conductances in protein-free lipid bilayers form from a mixture of zwitterionic phospholipids. The channel-forming activity of capsaicin and four of its analogs followed the sequence: resiniferatoxin > capsaicin = pelargonic acid vanillylamide > methylcapsaicin >> veratrylamine. The ability to form channels correlated with the biological activity of these compounds observed in other studies that measured 45Ca uptake into rat dorsal root ganglion cells. The correlation obtained suggests that an interaction with the lipid bilayer may be an important component of the biological activity of capsaicin.
Carbon-13 nuclear magnetic resonance studies of adenosylcobalamin and alkylcorrinoids, selectively enriched with carbon-13 (1975)

The carbon-13 nuclear magnetic resonance spectra of a series of alkylcorrinoids, selectively enriched with 13C in the alkyl ligand, were recorded at 25.2 MHz and 25 degrees. The nature of the axial ligands markedly affects the chemical shift of the labeled alkyl moiety (trans effect) as well as the 13C resonances of selected carbon atoms of the corrin ring (cis effect). Although a number of factors appear to influence the trans effect on the chemical shift of the alkyl ligand (important among them being electric field effects), the cis effect appears to be dominated by changes in charge density (at the methine bridge carbon atoms, C-5, C-10, C-15) and by steric effects (at the methyl groups at C-1, C-5, and C-15) accompanying axial ligation. Spin-latice relaxation times of several organocorrinoids, selectively labeled with 13C in the ligands attached to cobalt, were also measured. The T1 values of the methylene carbons of [5'-13C]adenosylcobalamin and [2-13C]carboxymethylcobalamin are very similar to that of the methine bridge carbon atom C-10 of the corrin ring, indicating that rotation about the carbon-cobalt bond of these two corrinoids is severely restricted. On the other hand, internal rotation about the carbon-cobalt bond of methylcobalamin is rapid.
Neural cell adhesion molecule‐mediated neurite outgrowth is repressed by overexpression of HES‐1 (2002)

The neural cell adhesion molecule (NCAM) stimulates neurite outgrowth by activating intracellular signaling cascades. We investigated the role of the transcriptional repressor HES-1 in NCAM-dependent neurite outgrowth by estimating neurite extension from PC12-E2 cells grown in coculture with NCAM-negative or NCAM-positive fibroblasts. PC12-E2 cells were transiently transfected with an expression plasmid encoding HES-1. We found that expression of HES-1 inhibited NCAM-dependent neurite outgrowth. Treatment with arachidonic acid (an important messenger in NCAM-dependent signaling) restored NCAM-induced neurite outgrowth inhibited by HES-1. These results suggest that HES-1 is a regulator of intracellular signal transduction stimulated by cell adhesion molecules involved in neurite outgrowth.
Signaling by two-component system noncognate partners promotes intrinsic tolerance to polymyxin B in uropathogenic Escherichia coli (2017)

Bacteria use two-component systems (TCSs) to react appropriately to environmental stimuli. Typical TCSs comprise a sensor histidine kinase that acts as a receptor coupled to a partner response regulator that coordinates changes in bacterial behavior, often through its activity as a transcriptional regulator. TCS interactions are typically confined to cognate pairs of histidine kinases and response regulators. We describe two distinct TCSs in uropathogenic Escherichia coli (UPEC) that interact to mediate a response to ferric iron. The PmrAB and QseBC TCSs were both required for proper transcriptional response to ferric iron. Ferric iron induced the histidine kinase PmrB to phosphotransfer to both its cognate response regulator PmrA and the noncognate response regulator QseB, leading to transcriptional responses coordinated by both regulators. Pretreatment of the UPEC strain UTI89 with ferric iron led to increased resistance to polymyxin B that required both PmrA and QseB. Similarly, pretreatment of several UPEC isolates with ferric iron increased tolerance to polymyxin B. This study defines physiologically relevant cross talk between TCSs in a bacterial pathogen and provides a potential mechanism for antibiotic resistance of some strains of UPEC.
Reversibly locking a protein fold in an active conformation with a disulfide bond: Integrin αL I domains with high affinity and antagonist activityin vivo (2001)

The integrin alphaLbeta2 has three different domains in its headpiece that have been suggested to either bind ligand or to regulate ligand binding. One of these, the inserted or I domain, has a fold similar to that of small G proteins. The I domain of the alphaM and alpha2 subunits has been crystallized in both open and closed conformations; however, the alphaL I domain has been crystallized in only the closed conformation. We hypothesized that the alphaL domain also would have an open conformation, and that this would be the ligand binding conformation. Therefore, we introduced pairs of cysteine residues to form disulfides that would lock the alphaL I domain in either the open or closed conformation. Locking the I domain open resulted in a 9,000-fold increase in affinity to intercellular adhesion molecule-1 (ICAM-1), which was reversed by disulfide reduction. By contrast, the affinity of the locked closed conformer was similar to wild type. Binding completely depended on Mg(2+). Orders of affinity were ICAM-1 > ICAM-2 > ICAM-3. The k(on), k(off), and K(D) values for the locked open I domain were within 1.5-fold of values previously determined for the alphaLbeta2 complex, showing that the I domain is sufficient for full affinity binding to ICAM-1. The locked open I domain antagonized alphaLbeta2-dependent adhesion in vitro, lymphocyte homing in vivo, and firm adhesion but not rolling on high endothelial venules. The ability to reversibly lock a protein fold in an active conformation with dramatically increased affinity opens vistas in therapeutics and proteomics.
MicroRNAs and future therapeutic applications in cancer. (2009)

Every cellular process is likely to be regulated by microRNAs (miRNAs), and an aberrant expression signature of these small non-coding RNAs is a hallmark of several diseases, including cancer. miRNA expression profiling by microarray techniques has provided a powerful tool to reveal the involvement of these tiny molecules in tumor development and progression, showing that they are differentially expressed in tumors as compared to normal tissues. Moreover, specific miRNA signatures have been associated with histopathological and clinical features, suggesting a potential role of these molecules as prognostic and predictive markers. Focusing then on their biological effects and role in cancer, it has been shown that miRNAs can function as potential oncogenes or oncosuppressor genes, depending on the cellular context and on the target genes they regulate. The possibility to modulate miRNA expression either in vitro and in vivo by developing synthetic pre-miRNA molecules or antisense oligonucleotides have at the same time provided a powerful tool to a deeper comprehension of the molecular mechanisms regulated by these molecules, and suggested the intriguing and promising perspective of their possible use in therapy. Herein we review our current knowledge about the involvement of miRNAs in cancer, and their potential as diagnostic, prognostic and therapeutic tools.
Binding of Cu(II) or Zn(II) in a de novo designed triple‐stranded α‐helical coiled‐coil toward a prototype for a metalloenzyme (2004)

We previously reported the IZ-3adH peptide, which formed a triple-stranded coiled-coil after binding Ni(II), Cu(II), or Zn(II). In this paper, we report the peptide, IZ-3aH, having a new metal binding specificity. The IZ-3aH peptide was found to bind Cu(II) and Zn(II) and form a triple-stranded coiled-coil. However, it did not bind Ni(II). Metal ion titrations monitored by circular dichroism revealed that the dissociation constants, K(d) were 9 microm for Zn(II) and 10 microm for Cu(II). The bound Cu(II) ion has a planar tetragonal geometry, where the coordination positions are three nitrogens of the His residues and one H(2)O.
Characterization of a novel thermophilic, cellulose-degrading bacterium Paenibacillus sp. strain B39 (2008)

Based on the ability to hydrolyse CMC and avicel, the cellulase produced by Paenibacillus sp. strain B39 would have potential applications in cellulose biodegradation.
Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C‐oxidase (1998)

Cytochrome P450 2A6 (CYP2A6) is a polymorphic enzyme responsible for the oxidation of certain precarcinogens and drugs and is the major nicotine C-oxidase. The role of CYP2A6 for nicotine elimination was emphasised recently by the finding that smokers carrying defective CYP2A6 alleles consumed fewer cigarettes [Pianezza et al. (1998) Nature 393, 750]. The method used for CYP2A6 genotyping has, however, been found to give erroneous results with respect to the coumarin hydroxylase phenotype, a probe reaction for the CYP2A6 enzyme. The present study describes an allele-specific PCR genotyping method that identifies the major defective CYP2A6 allele and accurately predicts the phenotype. An allele frequency of 1-3% was observed in Finnish, Spanish, and Swedish populations, much lower than described previously.
Prediction of the Coding Sequences of Unidentified Human Genes. IV. The Coding Sequences of 40 New Genes (KIAA0121-KIAA0160) Deduced by Analysis of cDNA Clones from Human Cell Line KG-1 (1995)

In this series of projects regarding the accumulation of sequence information of unidentified human genes, we newly deduced the sequences of 40 full-length cDNA clones of human cell line KG-1, and predicted the coding sequences of the corresponding genes, named KIAA0121 to 0160. The results of a computer search of public databases indicated that the sequences of 13 genes were unrelated to any reported genes, while the remaining 27 genes carried sequences which showed some similarities to known genes. Obvious unique sequences noted were as follows. A stretch of triplet repeats was contained in each of three genes: These were GAG(Glu) in KIAA0122 and KIAA0147, and TCC(Ser) in KIAA0150. A stretch of 10 amino acid-residues was repeated 21 times in KIAA0139, and a homologous sequence of 76-78 nucleotides was found repeated 6 times in the untranslated region of KIAA0125. Northern hybridization analysis demonstrated that 13 genes were expressed in a cell- or tissue-specific manner. Although a vast number of expressed sequence tags (ESTs) have been registered for comprehensive analysis of cDNA clones, our sequence data indicated that their distribution is very unbalanced: e.g. while no EST hit 7 genes, 85 ESTs fell in a single gene.
A Nerve Growth Factor-Induced Gene Encodes a Possible Transcriptional Regulatory Factor (1987)

Nerve growth factor (NGF) is a trophic agent that promotes the outgrowth of nerve fibers from sympathetic and sensory ganglia. The neuronal differentiation stimulated by this hormone was examined in the NGF-responsive cell line PC12. Differential hybridization was used to screen a complementary DNA library constructed from PC12 cells treated with NGF and cycloheximide. One of the complementary DNA clones that was rapidly induced by NGF was found to have a nucleotide sequence that predicts a 54-kilodalton protein with homology to transcriptional regulatory proteins. This clone, NGFI-A, contains three tandemly repeated copies of the 28- to 30-amino acid "zinc finger" domain present in Xenopus laevis TFIIIA and other DNA-binding proteins. It also contains another highly conserved unit of eight amino acids that is repeated at least 11 times. The NGFI-A gene is expressed at relatively high levels in the brain, lung, and superior cervical ganglion of the adult rat.
National Academy of Clinical Biochemistry Standards of Laboratory Practice: Recommendations for the Use of Cardiac Markers in Coronary Artery Diseases (1999)

The Sixth Conference on the "Standards of Laboratory Practice Series", sponsored by the National Academy of Clinical Biochemistry (NACB), was held on August 4-5, 1998, at the Annual Meeting of the American Association for Clinical Chemistry, in Chicago, IL. An expert committee was assembled to write recommendations on the use of cardiac markers in coronary artery diseases. The NACB Committee prepared a preliminary draft of the guidelines, made them available on the World Wide Web (www.nacb.org), and distributed them before the presentations. The recommendations were divided into four areas: the use of markers in the triage of patients with chest pain, acute coronary syndromes, clinical applications other than acute myocardial infarction and research, and assay platforms and markers of acute myocardial infarction. The recommendations were revised and subsequently re-presented in part at the "Biomarkers in Acute Cardiac Syndromes Conference", sponsored by the Jewish Hospital Heart and Lung Institute, Louisville KY, on October 16-17, 1998. This report lists each recommendation, its scientific justification, and a summary of discussions from conference participants and reviewers. Approximately 100 individuals responded to various versions of these recommendations via direct correspondences, telephone calls to Committee members, electronic mail correspondence to the Committee Chairman, or oral questions and comments raised during one of the two conference presentations. Some of the recommendations were changed to reflect the consensus opinion. In cases in which there was no consensus, the Committee included pertinent discussion without necessarily changing the original recommendations. At times, the Committee members felt that although a particular recommendation might not be the current standard of care today, they anticipate that it likely will be adopted in the near future.
Flexibility in peptide molecules and restraints imposed by hydrogen bonds, the AIB residue, and core inserts (1996)

The first segments of this article review some of the early crystal structure determinations of beta-bends, gamma-bends, large conformational changes in cyclic peptides upon complexation with metal ions, and both the stability and drastic change in conformation as a function of the solvent used for growing crystals. More recent structure analyses have concerned helical peptides containing the Aib and/or Dpg residues and associated conformational problems such as 310-/alpha-helix transitions, helix aberrations, reversals, severe curving of the helix, unfolding, and hydration of backbone. Ion channels occurring in three crystal forms of zervamicin and possible ion transport and gating mechanisms are described. Finally, hydrogen bonding patterns are presented in supramolecular assemblies of retropeptides with core inserts consisting of oxalyl, adipoyl, suberoyl and polymethylene moieties.
Donepezil Improves Cognition and Global Function in Alzheimer Disease<subtitle>A 15-Week, Double-blind, Placebo-Controlled Study</subtitle> (1998)

Donepezil hydrochloride (5 and 10 mg) administered once daily is a well-tolerated and efficacious agent for treating the symptoms of mild to moderately severe Alzheimer disease.