gebhart/patrepeval huggingface dataset:
Unraveling DNA helicases (2004)

DNA helicases are molecular 'motor' enzymes that use the energy of NTP hydrolysis to separate transiently energetically stable duplex DNA into single strands. They are therefore essential in nearly all DNA metabolic transactions. They act as essential molecular tools for the cellular machinery. Since the discovery of the first DNA helicase in Escherichia coli in 1976, several have been isolated from both prokaryotic and eukaryotic systems. DNA helicases generally bind to ssDNA or ssDNA/dsDNA junctions and translocate mainly unidirectionally along the bound strand and disrupt the hydrogen bonds between the duplexes. Most helicases contain conserved motifs which act as an engine to drive DNA unwinding. Crystal structures have revealed an underlying common structural fold for their function. These structures suggest the role of the helicase motifs in catalytic function and offer clues as to how these proteins can translocate and unwind DNA. The genes containing helicase motifs may have evolved from a common ancestor. In this review we cover the conserved motifs, structural information, mechanism of DNA unwinding and translocation, and functional aspects of DNA helicases.
双（3—三乙氧基甲硅烷基丙基）四硫烷对白炭黑补强丁苯橡胶性能的影响 (1999)

白炭黑是除炭黑外目前橡胶工业中采用的另一种经济实用的重要补强填料。白炭黑补强胶料的定伸应力一般低于炭黑补强胶料。但是,白炭黑能赋予撕裂强度、耐磨性、耐老化性和粘合性的独特性能组合。采用适当的硅烷偶联剂(如硫醇基硅烷、四硫代硅烷和偶氮硅烷)一般能提高白炭黑补强胶料的定伸应力。硅烷偶联剂含能与橡胶和白
Abstract 3620: LIV-1 antibody-drug conjugate: A novel therapeutic agent for breast and prostate cancer (2011)

Abstract LIV-1, also known as SLC39A6 or ZIP6, is a member of the zinc transporter family and was first identified as an estrogen-inducible gene in breast cancer. LIV-1, as a downstream target of STAT3, promotes the epithelial to mesenchymal transition that is important in the malignant progression to metastasis. Consistent with its role in cancer, we determined by immunohistochemical (IHC) analysis that LIV-1 is expressed by estrogen receptor-positive (ER+), hormone-treated tumors (both primary and metastatic sites) and ER-/PR-/Her2- (triple-negative) breast cancers. Hormone refractory metastatic prostate tumor samples express Liv-1, with expression confirmed in both bone and soft tissue metastatic sites by IHC. In healthy human tissues, LIV-1 expression is limited to hormonally-regulated organs (prostate, uterus, and breast). The broad expression of LIV-1 in prostate and breast cancer tumors in combination with the limited expression in vital organs makes LIV-1 an excellent target for an antibody-drug conjugate (ADC). We generated an ADC consisting of a humanized anti-LIV-1 mAb conjugated to the antitubulin agent monomethyl auristatin E (MMAE), via a plasma stable, enzyme-cleavable linker (vc). The humanized LIV-1 mAb bound with high affinity to both human and cynomolgous LIV-1. In vitro, anti-LIV-1-vcMMAE ADCs showed specific cytotoxic activity against a breast cancer cell line. In vivo studies also demonstrated antitumor activity of anti-LIV-1-vcMMAE ADCs in preclinical xenograft models with significant delay of tumor growth compared to control groups. These findings demonstrate that further evaluation and development of anti-LIV-1-vcMMAE is warranted as a promising and potential therapeutic agent for the treatment of prostate and ER+ and triple-negative breast cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3620. doi:10.1158/1538-7445.AM2011-3620
Characterization of the Butyrivibrio fibrisolvens glgB gene, which encodes a glycogen-branching enzyme with starch-clearing activity (1991)

A Butyrivibrio fibrisolvens H17c glgB gene, was isolated by direct selection for colonies that produced clearing on starch azure plates. The gene was expressed in Escherichia coli from its own promoter. The glgB gene consisted of an open reading frame of 1,920 bp encoding a protein of 639 amino acids (calculated Mr, 73,875) with 46 to 50% sequence homology with other branching enzymes. A limited region of 12 amino acids showed sequence similarity to amylases and glucanotransferases. The B. fibrisolvens branching enzyme was not able to hydrolyze starch but stimulated phosphorylase alpha-mediated incorporation of glucose into alpha-1,4-glucan polymer 13.4-fold. The branching enzyme was purified to homogeneity by a simple two-step procedure; N-terminal sequence and amino acid composition determinations confirmed the deduced translational start and amino acid sequence of the open reading frame. The enzymatic properties of the purified enzyme were investigated. The enzyme transferred chains of 5 to 10 (optimum, 7) glucose units, using amylose and amylopetin as substrates, to produce a highly branched polymer.
Zirconium‐Metalloporphyrin PCN‐222: Mesoporous Metal–Organic Frameworks with Ultrahigh Stability as Biomimetic Catalysts (2012)

Biomimetisches MOF: Die hochstabilen MOFs PCN-222(M) (M=Fe, Mn, Co, Ni, Cu und Zn) mit offenen Metallzentren und besonders großen 1D-Kanälen enthalten achtfach verknüpfte Zr6-Cluster und redoxaktive Metalloporphyrinmotive. PCN-222(Fe) zeigt Peroxidase-ähnliche Aktivität in wässriger Lösung und oxidiert eine Reihe von Substraten hocheffizient in biomimetischer Weise.
New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function--a study in normals and dilated cardiomyopathy. (1995)

Because systolic and diastolic dysfunction frequently coexist, it is hypothesized that a combined measure of left ventricular chamber performance may be more reflective of overall cardiac dysfunction than systolic or diastolic measures alone. METHODS Study patients consisted of 170 subjects: 70 normals, 47 patients with severe dilated cardiomyopathy in NYHA class III-IV awaiting cardiac transplantation and 53 patients with idiopathic dilated cardiomyopathy of intermediate severity [NYHA class II, ejection fractions (EF) 30-50%]. EF, stroke volume and cardiac indexes were measured using conventional echo-Doppler methods. Pre-ejection period/ejection time (PEP/ET), isovolumetric relaxation time (IRT), isovolumetric contraction time/ET (ICT/ET) were also measured. A new derived index of myocardial performance: (ICT+IRT)/ET, was obtained by subtracting ET from the interval between cessation and onset of the mitral inflow velocity to give the sum of ICT and IRT. RESULTS The index was easily measured, reproducible, and had a narrow range in normals. The mean value of the index was significantly different between normal, intermediate and pre-transplant subjects (0.39 +/- 0.05, 0.59 +/- 0.10 and 1.06 +/- 0.24, respectively, p < 0.001 for all comparisons). The degree of inter-group overlap was smaller for the index compared to PEP/ET, ICT/ET and other parameters. Within functional groups, the value of the index did not appear to be related to heart rate, mean arterial pressure and the degree of mitral regurgitation. CONCLUSION (ICT+IRT)/ET is a conceptually new, simple and reproducible Doppler index of combined systolic and diastolic myocardial performance in patients with primary myocardial systolic dysfunction.
CNMGRAF—graphic presentation services for network management (1985)

Two key problems in the design of systems and network management applications are: how to efficiently manage large quantities of related data, and how to allow the application user to view this data at a user-defined level of detail. This paper describes an architecture for network management facilities that may help solve these problems. It also describes CNMgraf (Communications Network Management Graphics Facility), which was developed to test the presentation service model defined by this architecture.
Proteomics: Capacity versus utility (2000)

Until recently scientists studied genes or proteins one at a time. With improvements in technology, new tools have become available to study the complex interactions that occur in biological systems. Global studies are required to do this, and these will involve genomic and proteomic approaches. High-throughput methods are necessary in each case because the number of genes and proteins in even the simplest of organisms are immense. In the developmental phase of genomics, the emphasis was on the generation and assembly of large amounts of nucleic acid sequence data. Proteomics is currently in a phase of technological development and establishment, and demonstrating the capacity for high throughput is a major challenge. However, funding bodies (both in the public and private sector) are increasingly focused on the usefulness of this capacity. Here we review the current state of proteome research in terms of capacity and utility.
The role of IL-17 and family members in the pathogenesis of arthritis. (2003)

Interleukin (IL)-17 is a T-cell-derived cytokine that is expressed in the synovium of patients with arthritis. IL-17 contributes to the pathogenesis of arthritis, and demonstrates additive or even synergistic effects with IL-1 and tumor necrosis factor (TNF) in inducing joint pathology. It is a potent inducer of receptor activator of nuclear factor-kappa B. IL-17 also has the capacity to induce joint destruction in an IL-1-independent manner. The discovery of IL-17 family members may further elucidate the role of this cytokine family in arthritis pathology, with IL-17F a promising candidate. Anti-IL-17 cytokine therapy may be an interesting new antirheumatic approach to the prevention of joint destruction, in addition to anti-TNF and anti-IL-1 therapy.
Site-specific prodrug activation by antibody-beta-lactamase conjugates: regression and long-term growth inhibition of human colon carcinoma xenograft models. (1993)

Antibody-directed catalysis (ADC) is a two-step method for the delivery of chemotherapeutic agents in which enzyme-antibody conjugate, prelocalized to antigen-bearing tumor cells, catalyzes the site-specific conversion of prodrug to drug. An ADC system consisting of F(ab')-beta-lactamase conjugates and a cephalosporin derivative of the oncolytic agent 4-desacetylvinblastine-3-carboxhydrazide was investigated. The ability of the system to mediate antitumor activity was compared with that of free drug given alone and with covalent drug-antibody conjugates in LS174T and T380 colon carcinoma xenografts in nude mice. Efficacy increased from moderate tumor growth inhibition by using free 4-desacetylvinblastine-3-carboxhydrazide to tumor regression and long-term stabilization with the ADC system. Labile covalent drug-antibody conjugates prepared from the same antibodies were less effective than ADC and required much higher antibody doses. The antigens KS1/4, carcinoembryonic antigen, and tumor-associated glycoprotein-72, TAG-72, present on the model cell lines, were chosen to investigate the effect of differences in subcellular location and expression heterogeneity on the efficacy of ADC delivery. Response was equivalent with the three tumor antigens. Hence, heterogeneous expression and membrane shedding of carcinoembryonic antigen and TAG-72, did not diminish the suitability of these antigens as targets for ADC therapy. In contrast, drug-antibody conjugate efficacy was more sensitive to subcellular location and heterogeneity. Thus, ADC is a highly effective form of immunochemotherapy in preclinical models, with applicability toward a variety of antigen targets.
Rescue of a mitochondrial deficiency causing Leber hereditary optic neuropathy (2002)

A G to A transition at nucleotide 11778 in the ND4 subunit gene of complex I was the first point mutation in the mitochondrial genome linked to a human disease. It causes Leber Hereditary Optic Neuropathy, a disorder with oxidative phosphorylation deficiency. To overcome this defect, we made a synthetic ND4 subunit compatible with the "universal" genetic code and imported it into mitochondria by adding a mitochondrial targeting sequence. For detection we added a FLAG tag. This gene was inserted in an adeno-associated viral vector. The ND4FLAG protein was imported into the mitochondria of cybrids harboring the G11778A mutation, where it increased their survival rate threefold, under restrictive conditions that forced the cells to rely predominantly on oxidative phosphorylation to produce ATP. Since assays of complex I activity were normal in G11778A cybrids we focused on changes in ATP synthesis using complex I substrates. The G11778A cybrids showed a 60% reduction in the rate of ATP synthesis. Relative to mock-transfected G11778A cybrids, complemented G11778A cybrids showed a threefold increase in ATP synthesis, to a level indistinguishable from that in cybrids containing normal mitochondrial DNA. Restoration of respiration by allotopic expression opens the door for gene therapy of Leber Hereditary Optic Neuropathy.
Pulmonary Interleukin-23 Gene Delivery Increases Local T-Cell Immunity and Controls Growth ofMycobacterium tuberculosisin the Lungs (2005)

Interleukin-23 (IL-23) is a heterodimeric cytokine that shares IL-12 p40 but contains a unique p19 subunit similar to IL-12 p35. Previous studies indicate a greater importance for intact IL-12/23 p40 expression than IL-12 p35 for immunity against Mycobacterium tuberculosis, suggesting a role for IL-23 in host defense. The effects of IL-23 on the outcome of pulmonary infection with M. tuberculosis have not been described. Here, we show that local delivery of replication-defective adenovirus vectors encoding IL-23 (AdIL-23) greatly stimulated expression of both gamma interferon (IFN-gamma) and IL-17 in lung tissues of otherwise normal mice. When given 72 h prior to infection with M. tuberculosis, AdIL-23 significantly reduced the bacterial burden at 14, 21, and 28 days. Markedly lower levels of lung inflammation were observed at 28 days than in control mice pretreated with control adenovirus (AdNull) or vehicle controls. AdIL-23 pretreatment resulted in increased numbers of CD4(+) CD25(+) activated T cells in lungs and draining lymph nodes compared to control groups and more CD4(+) T cells bearing surface memory markers in lung lymph nodes. IL-23 gene delivery also significantly enhanced host anti-mycobacterial T-cell responses, as shown by elevated levels of IFN-gamma and IL-17 secreted in vitro following restimulation with M. tuberculosis purified protein derivative. Overall, our data show that transient IL-23 gene delivery in the lung is well tolerated, and they provide the initial demonstration that this factor controls mycobacterial growth while augmenting early pulmonary T-cell immunity.
Radiation characteristics of thin-wire ternaryfractal trees (1999)

The multiband electromagnetic behaviour of thin-wire structures based on a ternary tree fractal geometry are investigated. As an example, experimental and numerical results are presented for the particular case of a three-band monopole structure, which show the expected self-similar behaviour at those bands. Some interesting properties are observed for these ternary tree fractal structures that are not evident in their Sierpinski monopole counterparts.
Synthesis and antiarrhythmic activity of new [(dialkylamino)alkyl]pyridylacetamides (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and antiarrhythmic activity of new [(dialkylamino)alkyl]pyridylacetamidesClaude A. Bernhart, Christian Condamine, Henri Demarne, Romeo Roncucci, Jean Pierre Gagnol, Patrick J. Gautier, and Martine A. SerreCite this: J. Med. Chem. 1983, 26, 3, 451–455Publication Date (Print):March 1, 1983Publication History Published online1 May 2002Published inissue 1 March 1983https://pubs.acs.org/doi/10.1021/jm00357a026https://doi.org/10.1021/jm00357a026research-articleACS PublicationsRequest reuse permissionsArticle Views426Altmetric-Citations20LEARN 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
Vesicular Stomatitis Virus-Based Vaccine Protects Hamsters against Lethal Challenge with Andes Virus (2011)

Andes virus (ANDV) is a highly pathogenic South American hantavirus that causes hantavirus pulmonary syndrome (HPS). A high case fatality rate, the potential for human-to-human transmission, the capacity to infect via aerosolization, and the absence of effective therapies make it imperative that a safe, fast-acting, and effective ANDV vaccine be developed. We generated and characterized a recombinant vesicular stomatitis virus (VSV) vector expressing the ANDV surface glycoprotein precursor (VSVΔG/ANDVGPC) as a possible vaccine candidate and tested its efficacy in the only lethal-disease animal model of HPS. Syrian hamsters immunized with a single injection of VSVΔG/ANDVGPC were fully protected against disease when challenged at 28, 14, 7, or 3 days postimmunization with a lethal dose of ANDV; however, the mechanism of protection seems to differ depending on when the immunization occurs. At 28 days postimmunization, a lack of detectable ANDV RNA in lung, liver, and blood tissue samples, as well as a lack of seroconversion to the ANDV nucleocapsidprotein in nearly all animals, suggested largely sterile immunity. The vaccine was able to generate high levels of neutralizing anti-ANDV G(N)/G(C) antibodies, which seem to play a role as a mechanism of vaccine protection. Administration of the vaccine at 7 or 3 days before challenge also resulted in full protection but with no specific neutralizing humoral immune response, suggesting a possible role of innate responses in protection against challenge virus replication. Administration of the vaccine 24 h postchallenge was successful in protecting 90% of hamsters and again suggested the induction of a potent antiviral state by the recombinant vector as a potential mechanism. Overall, our data suggest the potential for the use of the VSV platform as a fast-acting and effective prophylaxis/postexposure treatment against lethal hantavirus infections.
Bacterial Vaginosis Is a Strong Predictor ofNeisseria gonorrhoeaeandChlamydiatrachomatisInfection (2003)

To evaluate whether bacterial vaginosis predicts the acquisition of sexually transmitted diseases (STDs), we studied 255 nonpregnant female subjects aged 15-30 who reported recent sexual contact with a male partner in whom either gonococcal or chlamydial urethritis or nongonococcal urethritis was diagnosed. Compared to subjects with normal vaginal flora, subjects with bacterial vaginosis were more likely to test positive for Neisseria gonorrhoeae (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.7-9.7) and Chlamydia trachomatis (OR, 3.4; 95% CI, 1.5-7.8). Subjects colonized vaginally by hydrogen peroxide-producing lactobacilli were less likely to receive a diagnosis of chlamydial infection or gonorrhea than subjects without such lactobacilli. Bacterial vaginosis was a strong predictor of gonorrhea and chlamydial infection among subjects who reported recent exposure to a male partner with urethritis. These data support the importance of vaginal flora in the defense against STD acquisition.
Novel Pathway of Salicylate Degradation by Streptomyces sp. Strain WA46 (2004)

A novel salicylate-degrading Streptomyces sp., strain WA46, was identified by UV fluorescence on solid minimal medium containing salicylate; trace amounts of gentisate were detected by high-pressure liquid chromatography when strain WA46 was grown with salicylate. PCR amplification of WA46 DNA with degenerate primers for gentisate 1,2-dioxygenase (GDO) genes produced an amplicon of the expected size. Sequential PCR with nested GDO primers was then used to identify a salicylate degradation gene cluster in a plasmid library of WA46 chromosomal DNA. The nucleotide sequence of a 13.5-kb insert in recombinant plasmid pWD1 (which was sufficient for the complete degradation of salicylate) showed that nine putative open reading frames (ORFs) (sdgABCDEFGHR) were involved. Plasmid pWD1 derivatives disrupted in each putative gene were transformed into Streptomyces lividans TK64. Disruption of either sdgA or sdgC blocked salicylate degradation; constructs lacking sdgD accumulated gentisate. Cell extracts from Escherichia coli DH5 alpha transformants harboring pUC19 that expressed each of the sdg ORFs showed that conversions of salicylate to salicylyl-coenzyme A (CoA) and salicylyl-CoA to gentisyl-CoA required SdgA and SdgC, respectively. SdgA required CoA and ATP as cofactors, while NADH was required for SdgC activity; SdgC was identified as salicylyl-CoA 5-hydroxylase. Gentisyl-CoA underwent spontaneous cleavage to gentisate and CoA. SdgA behaved as a salicylyl-CoA ligase despite showing amino acid sequence similarity to an AMP-ligase. SdgD was identified as a GDO. These results suggest that Streptomyces sp. strain WA46 degrades salicylate by a novel pathway via a CoA derivative. Two-dimensional polyacrylamide gel electrophoresis and reverse transcriptase-PCR studies indicated that salicylate induced expression of the sdg cluster.
Rapid Intradermal Delivery of Liquid Formulations Using a Hollow Microstructured Array (2010)

3M's hMTS can provide rapid, intradermal delivery of 300-1,500 µL of liquid formulations of small molecules salts and proteins, compounds not typically compatible with passive transdermal delivery.
New insights into paroxysmal nocturnal hemoglobinuria (2001)

The characteristic, defining defect in paroxysmal nocturnal hemoglobinuria is the somatic mutation of the PIG-A gene (essential to the biosynthesis of the glycosylphosphatidylinositol moiety that affixes a number of proteins to the cellular surface) in hematopoietic cells. These cells thus lack the proteins usually held in place by this anchor. The absence of these proteins is the most reliable diagnostic criterion of the disease and is responsible for many of the clinical manifestations of PNH. The current hypothesis explaining the disorder suggests that there are two components: (1) hematopoietic stem cells with the characteristic defect are present in the marrow of many if not all normal individuals in very small numbers; (2) some aplastogenic influence suppresses the normal stem cells but does not suppress the defective stem cells, thus allowing the proportion of these cells to increase. Current research attempts to substantiate this hypothesis and design therapy consistent with the hypothesis. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem cell disorder characterized by intravascular hemolysis, hypercoagulability, and relative bone marrow failure [1]. It is characterized by a somatic mutation in the gene encoding the alpha1-6-N-acetylglucosaminyltransferase necessary for the formation of the glycosylphosphatidylinositol (GPI) anchor that binds certain proteins to the membrane surface (Fig. 1) [2,3*]. Whereas many of the manifestations can be accounted for by the absence of these proteins on the cells of the hematopoietic system, it is not entirely clear whether this defect is sufficient to make the disease manifest. In this paper, the author reviews recent clinical observations and relates them to the underlying pathophysiology of the disease.