gebhart/patrepeval huggingface dataset:
Limited proteolysis of tetanus toxin (1991)

Tetanus toxin is synthesized by Clostridium tetani as a 151-kDa peptide chain. The primary gene product is processed post-translationally by removal of the initiating methionine residue, formation of disulfide bridges and limited proteolysis by bacterial or exogenous proteinases. The mature toxins consist of a 52-kDa light chain and a 98-kDa heavy chain, linked together by a disulfide bond. Proteolytic nicking is accompanied by increased pharmacological potency. To identify the structural alterations involved, single-chain toxin has been subjected to limited proteolysis with various enzymes. The new N-termini have been determined by Edman degradation and the C-termini by isolation of short C-terminal peptide fragments and subsequent analysis of the sequence and composition. All two-chain toxins result from proteolytic nicking within the 17-residue segment of residues 445-461. Thus, the protease(s) of the culture broth cleave on the C-terminal side of Glu449 and partially Ala456, giving rise to two heavy chain N-termini. Trypsin and clostripain first attack the C-terminal of Arg454 and later Arg448, whereas endoproteinase Arg-C cleaves the former bond only. Chymotrypsin and endoproteinase Glu-C each split a single peptide bond, i.e. that located after Tyr452 and Glu449, respectively. Papain gives rise to a large number of cleavages within the 17-residue segment, the new C-terminus being Thr445 or Asn446 and the new N-terminus being Asp460 or Leu461. Further papain digestion leads to an additional cleavage within the heavy chain between Ser863 and Lys864. The original N-terminal Pro1 and C-terminal Asp1314, predicted from the nucleotide sequence, are conserved in all proteolytic digests. The pharmacological activity of the various two-chain toxins was 5-11 times that of the single-chain toxin, as estimated from the inhibition of [3H]noradrenaline release from rat-brain homogenate. The present data on the processing and activation by limited proteolysis prove the existence of several active tetanus isotoxins. These data, together with our previous data on the localization of disulfide bridges and sulfhydryl groups (Krieglstein, K., Henschen, A., Weller, U. & Habermann, E. (1990) Eur. J. Biochem. 188, 39-45), provide the detailed protein chemical characterization of the tetanus isotoxins.
Demand response via large scale charging of electric vehicles (2016)

The problem of centralized scheduling of large scale charging of electric vehicles (EVs) with demand response options is considered. A stochastic dynamic programming model is introduced in which the EV charging service provider faces stochastic demand, convex non-completion penalties, and random demand response requirements. Formulated as a restless multi-armed bandit problem, the EV charging problem is shown to be indexable, thus low complexity index policies exist. An enhancement of the Whittle's index policy based on spatial interchange according to the less laxity and longer processing time (LLLP) principle is presented. Numerical results illustrate the performance improvement and the capability of handling various operation uncertainties of the proposed index policy.
Standard- vs High-Dose Clopidogrel Based on Platelet Function Testing After Percutaneous Coronary Intervention (2011)

clinicaltrials.gov Identifier: NCT00645918.
Diagnostic Accuracy of a Machine-Learning Approach to Coronary Computed Tomographic Angiography–Based Fractional Flow Reserve (2018)

On-site CT-FFR based on ML improves the performance of CTA by correctly reclassifying hemodynamically nonsignificant stenosis and performs equally well as CFD-based CT-FFR.
Prostate-Specific Antigen and Premalignant Change: Implications for Early Detection (1989)

PSA represents a major advance in our tumor marker armamentarium. PIN fulfills the majority of requirements for a premalignant change. If we could determine a subset of individuals with PIN, an enriched population on which to base screening studies would emerge. In this regard the observation that PIN may be associated with elevation of the serum PSA is particularly intriguing. Considerable interest exists for early detection of prostate cancer. The high morbidity and mortality associated with this tumor coupled with the late stage at presentation by conventional means underscore the justification for such enthusiasm. However, the wisdom of screening for a cancer for which the mortality is far less than the histologic incidence remains to be proven. In the final analysis, the question is not whether we can detect more carcinoma, but rather whether we can significantly decrease patient morbidity and mortality. Until prospective randomized clinical trials demonstrate the effectiveness of early detection programs for carcinoma of the prostate, it is difficult to recommend such screening to the general public.
RUTHENIUM (2003)

RETURN TO ISSUEPREVNewsNEXTRUTHENIUMROBERT H. GRUBBSView Author Information CALIFORNIA INSTITUTE OF TECHNOLOGYCite this: Chem. Eng. News 2003, 81, 36, 112Publication Date (Print):September 8, 2003Publication History Published online13 November 2010Published inissue 8 September 2003https://doi.org/10.1021/cen-v081n036.p112Copyright © 2003 AMERICAN CHEMICAL SOCIETYArticle Views66Altmetric-Citations6LEARN 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 (811 KB) SUBJECTS:Ruthenium Get e-Alerts
Percutaneous implantation of a biological valve in the aorta to treat aortic valve insufficiency -- a sheep study. (2002)

Percutaneously implanted valves in the thoracic aorta of sheep with massive aortic insufficiency function well in the acute study. In comparison to previous surgical results, this technique might become an alternative to surgery in patients with chronic aortic insufficiency in whom perioperative risks are high.
Carboplatin in the treatment of squamous cell head and neck cancers. (1992)

Cancer of the head and neck, or aerodigestive tract, represents only a small percentage of all cancer cases in the United States, yet its variable presentations have wide-ranging implications that make it one of the most problematic cancers. Recent research has focused on treatment approaches for the patient with advanced disease. Encouraging results have been noted with combination cisplatin/5-fluorouracil (5-FU) and, more recently, with carboplatin/5-FU, particularly in previously untreated patients. The carboplatin-containing regimen has several important advantages over that with cisplatin, including outpatient administration and less severe nausea and vomiting, an important consideration in terms of nutritional support for head and neck cancer patients. The demonstration of possible synergistic activity between platinum compounds and radiation therapy also has prompted considerable interest, as such a combined-modality approach offers the potential for improved quality of life in patients with head and neck cancers. Carboplatin is an excellent agent for the treatment of squamous cell head and neck cancers, with recognized single-agent activity and a high degree of efficacy, when combined with 5-FU. Carboplatin can be combined effectively with concurrent radiotherapy and, with its advantages over cisplatin, is increasingly used as part of initial therapy for head and neck cancers.
Direct Interaction of SRY-Related Protein SOX9 and Steroidogenic Factor 1 Regulates Transcription of the Human Anti-Müllerian Hormone Gene (1998)

For proper male sexual differentiation, anti-Müllerian hormone (AMH) must be tightly regulated during embryonic development to promote regression of the Müllerian duct. However, the molecular mechanisms specifying the onset of AMH in male mammals are not yet clearly defined. A DNA-binding element for the steroidogenic factor 1 (SF-1), a member of the orphan nuclear receptor family, located in the AMH proximal promoter has recently been characterized and demonstrated as being essential for AMH gene activation. However, the requirement for a specific promoter environment for SF-1 activation as well as the presence of conserved cis DNA-binding elements in the AMH promoter suggest that SF-1 is a member of a combinatorial protein-protein and protein-DNA complex. In this study, we demonstrate that the canonical SOX-binding site within the human AMH proximal promoter can bind the transcription factor SOX9, a Sertoli cell factor closely associated with Sertoli cell differentiation and AMH expression. Transfection studies with COS-7 cells revealed that SOX9 can cooperate with SF-1 in this activation process. In vitro and in vivo protein-binding studies indicate that SOX9 and SF-1 interact directly via the SOX9 DNA-binding domain and the SF-1 C-terminal region, respectively. We propose that the two transcription factors SOX9 and SF-1 could both be involved in the expression of the AMH gene, in part as a result of their respective binding to the AMH promoter and in part because of their ability to interact with each other. Our work thus identifies SOX9 as an interaction partner of SF-1 that could be involved in the Sertoli cell-specific expression of AMH during embryogenesis.
Amine effect on phenylboronic acid complex with glucose under physiological pH in aqueous solution (1996)

A new "intelligent' polymer system was developed utilizing the binding and exchange of phenylboronic acid (PBA) with polyols and/or glucose. In this improved system, an amine component was incorporated into the polymer chain along with PBA, to enhance binding between PBA and glucose under physiological conditions. The PBA-based polymer was formed by free-radical copolymerization of 3-methacrylamidophenylboronic acid (MAPB) with comonomers, N,N-dimethylaminopropylacrylamide (DMAPAA) and acrylamide (AAm) in the presence of N,N'-methylenebis(acrylamide) (Bis-AAm) as a cross-linker. The proportion of the amount of PBA groups complexed with glucose vs total amount of PBA groups was determined by the batch method. Compared to PBA copolymers synthesized without amine component, the proportion increased as a function of the amine content as well as the pH of the buffer. These results confirm that the interaction of neighboring amines (unprotonated) to PBA strengthens the binding with glucose, especially at pH 7.4 and above. This new PBA-amine copolymer is promising as a material useful for polyol separation, protection of polyols, and possibly, as an insulin delivery device.
Release of lymphokines after infection with Epstein Barr virus in vitro. II. A monocyte-dependent inhibitor of interleukin 1 downregulates the production of interleukin 2 and interferon-gamma in rheumatoid arthritis. (1986)

Epstein Barr virus (EBV)-infection of normal peripheral blood mononuclear cells (PBMC) in vitro induces IFN-alpha secretion from B cell and natural killer (NK) cell populations, and IFN-gamma secretion from T cells. IFN-gamma depends on prior elaboration of IL 2 and IL 1 that originates from monocytes and NK cells. PBMC from rheumatoid arthritis (RA) patients released moderately elevated levels of IFN-alpha (236 +/- 62 U/ml vs 168 +/- 34 in normals). In contrast, IFN-gamma was significantly lower in RA (88 +/- 34 U/ml vs 209 +/- 32) with an associated deficit in IL 2. A monocyte-dependent factor was shown to be responsible for this deficit, since monocyte depletion of RA cultures normalized the levels of IL 2 and IFN-gamma. Significantly lower levels of IL 1 activity were present in the supernatants of RA PBMC cultures as compared with normal cultures, and this was shown to be associated with presence of a nondialyzable IL 1 inhibitor. This inhibitor was capable of preventing the IL 1-dependent synthesis of IL 2 and IFN-gamma by normal PBMC. Exogenous IL 1 or IL 2 restored the deficient IFN-gamma secretion in RA PBMC. Thus, the deficient ability of RA lymphocytes to control EBV infection may be secondary to impairment of a monocyte-T cell interaction at the level of IL 1.
Movers and shakers: cell cytoskeleton in cancer metastasis (2014)

This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24.
Contributions of Two Nuclear Localization Signals of Influenza A Virus Nucleoprotein to Viral Replication (2006)

The RNA genome of influenza A virus, which forms viral ribonucleoprotein complexes (vRNPs) with viral polymerase subunit proteins (PA, PB1, and PB2) and nucleoprotein (NP), is transcribed and replicated in the nucleus. NP, the major component of vRNPs, has at least two amino acid sequences that serve as nuclear localization signals (NLSs): an unconventional NLS (residues 3 to 13; NLS1) and a bipartite NLS (residues 198 to 216; NLS2). Although both NLSs are known to play a role in nuclear transport, their relative contributions to viral replication are poorly understood. We therefore investigated their contributions to NP subcellular/subnuclear localization, viral RNA (vRNA) transcription, and viral replication. Abolishing the unconventional NLS caused NP to localize predominantly to the cytoplasm and affected its activity in vRNA transcription. However, we were able to create a virus whose NP contained amino acid substitutions in NLS1 known to abolish its nuclear localization function, although this virus was highly attenuated. These results indicate that while the unconventional NLS is not essential for viral replication, it is necessary for efficient viral mRNA synthesis. On the other hand, the bipartite NLS, whose contribution to the nuclear transport of NP is limited, was essential for vRNA transcription and NP's nucleolar accumulation. A virus with nonfunctional NLS2 could not be generated. Thus, the bipartite NLS, but not the unconventional NLS, of NP is essential for influenza A virus replication.
Delayed childbearing: more women are having their first child later in life. (2009)

Of particular interest to both researchers and the public is the "average" age of women when they have a child, especially their first. Age at first birth influences the total number of births that a woman might have in her life, which impacts the size, composition, and future growth of the population. The age of the mother, both younger and older, plays a strong role in a wide range of birth outcomes (e.g., birthweight, multiple births, and birth defects), so it is critical to track the average age at which women have their first birth.
A Four-Base Paired Genetic Helix with Expanded Size (2003)

We describe a new molecular class of genetic-pairing system that has a native DNA backbone but has all four base pairs replaced by new, larger pairs. The base pairs include size-expanded analogs of thymine and of adenine, both extended by the width of a benzene ring (2.4 A). The expanded-diameter double helices are more thermodynamically stable than the Watson-Crick helix, likely because of enhanced base stacking. Structural data confirm a right-handed, double-stranded, and base-paired helical form. Because of the larger base size, all the pairs of this helical system are fluorescent, which suggests practical applications in detection of natural DNA and RNA. Our findings establish that there is no apparent structural or thermodynamic prohibition against genetic systems having sizes different from the natural one.
The Transcriptional Landscape of the Yeast Genome Defined by RNA Sequencing (2008)

The identification of untranslated regions, introns, and coding regions within an organism remains challenging. We developed a quantitative sequencing-based method called RNA-Seq for mapping transcribed regions, in which complementary DNA fragments are subjected to high-throughput sequencing and mapped to the genome. We applied RNA-Seq to generate a high-resolution transcriptome map of the yeast genome and demonstrated that most (74.5%) of the nonrepetitive sequence of the yeast genome is transcribed. We confirmed many known and predicted introns and demonstrated that others are not actively used. Alternative initiation codons and upstream open reading frames also were identified for many yeast genes. We also found unexpected 3'-end heterogeneity and the presence of many overlapping genes. These results indicate that the yeast transcriptome is more complex than previously appreciated.
Immunity to influenza in ferrets. II. Influence of adjuvants on immunization. (1972)

Immunization of ferrets with a single intramuscular inoculation of killed A2/Hong Kong virus did not induce serum or nasal antibody, and these animals were found to be completely susceptible to subsequent infection with virulent influenza virus A2/Hong Kong/3/68. A similar result was found for ferrets immunized with 2 inoculations of killed virus vaccine given 2 weeks apart. Ferrets immunized with killed A2/Hong Kong virus in conjunction with Bordetella pertussis produced relatively low levels of serum HI antibody to A2/Hong Kong virus; when infected with virulent influenza virus, these ferrets showed a modified reaction, with a less marked febrile reaction than was observed for non-immunized animals. Immunization of ferrets with killed A2/Hong Kong virus in Freund's complete adjuvant resulted in the production of relatively high levels of serum HI antibody, but no detectable nasal antibody. These animals were shown to be partially immune to subsequent infection with virulent influenza virus. However, although the serum antibody levels of these animals following immunization was comparable to that found following infection with live virus, the degree of immunity to infection with virulent influenza virus was measurably less.
Fetal-Specific DNA Methylation Ratio Permits Noninvasive Prenatal Diagnosis of Trisomy 21 (2011)

The standard procedures for prenatal genetic diagnosis of trisomy 21 (or Down syndrome) are invasive techniques based on cytogenetic or DNA analyses. Fetal genetic material with these techniques is obtained by amniocentesis, chorionic villus sampling, or cordocentesis, and there is significant risk of miscarriages of normal pregnancies. Safer alternatives investigated include a promising test for noninvasive prenatal diagnosis of trisomy 21 that can detect methylation differences (differentially methylated regions) between the free-fetal DNA in the maternal circulation among cases with and without trisomy 21. The test combines methylated DNA immunoprecipitation (MeDIP) methodology with real-time quantitative PCR to distinguish fetal DNA of trisomy 21 cases from normal cases. Worldwide trials have demonstrated that this test (called MeDIP) has considerable medical and commercial potential for noninvasive prenatal diagnosis of trisomy 21 as an alternative to invasive diagnostic procedures. The aim of this study was to demonstrate the efficacy of this test to discriminate between trisomy 21 and normal cases among blind samples. DNA methylation ratio values were determined for 40 blind and 40 known samples of free fetal DNA obtained from normal and trisomy 21 cases. The test correctly identified all 40 blind samples of the fetal-specific differentially methylated regions. There were 14 cases of trisomy 21 and 26 normal cases. These findings demonstrate that application of MeDIP in combination with real-time quantitative PCR is an accurate procedure for noninvasive prenatal detection of trisomy 21 and has future potential for routine testing of all pregnancies.
ChemInform Abstract: ADRIAMYCIN ANALOGS. 2. SYNTHESIS OF 13‐DEOXYANTHRACYCLINES (1978)

Abstract Aus Rhodomycinon (Ia) erhält man über (Ib) das Glykosid (Ic).
Toxin Gene Expression by Shiga Toxin-Producing Escherichia coli: the Role of Antibiotics and the Bacterial SOS Response (2000)

Toxin synthesis by Shiga toxin-producing Escherichia coli (STEC) appears to be coregulated through induction of the integrated bacteriophage that encodes the toxin gene. Phage production is linked to induction of the bacterial SOS response, a ubiquitous response to DNA damage. SOS-inducing antimicrobial agents, particularly the quinolones, trimethoprim, and furazolidone, were shown to induce toxin gene expression in studies of their effects on a reporter STEC strain carrying a chromosome-based stx2::lacZ transcriptional fusion. At antimicrobial levels above those required to inhibit bacterial replication, these agents are potent inducers (up to 140-fold) of the transcription of type 2 Shiga toxin genes (stx2); therefore, they should be avoided in treating patients with potential or confirmed STEC infections. Other agents (20 studied) and incubation conditions produced significant but less striking effects on stx2 transcription; positive and negative influences were observed. SOS-mediated induction of toxin synthesis also provides a mechanism that could exacerbate STEC infections and increase dissemination of stx genes. These features and the use of SOS-inducing antibiotics in clinical practice and animal husbandry may account for the recent emergence of STEC disease.
A novel sine wave in AC to DC converter with high frequency transformer isolation (1985)

A novel Switch-Mode-Rectifier (SMR) Structure is proposed and analyzed in this paper. The proposed converter structure employs a High-Frequency Sine PWM cycloconverter to provide high frequency ohmic isolation between the source and the load. Furthermore, it draws high quality current from the AC source thus requiring only small input reactive components. Consequently, the proposed converter structure exhibits high power density and has low implementation cost.
Mucosal delivery of vaccines in domestic animals (2006)

Mucosal vaccination is proving to be one of the greatest challenges in modern vaccine development. Although highly beneficial for achieving protective immunity, the induction of mucosal immunity, especially in the gastro-intestinal tract, still remains a difficult task. As a result, only very few mucosal vaccines are commercially available for domestic animals. Here, we critically review various strategies for mucosal delivery of vaccines in domestic animals. This includes live bacterial and viral vectors, particulate delivery-systems such as polymers, alginate, polyphosphazenes, immune stimulating complex and liposomes, and receptor mediated-targeting strategies to the mucosal tissues. The most commonly used routes of immunization, strategies for delivering the antigen to the mucosal surfaces, and future prospects in the development of mucosal vaccines are discussed.