gebhart/patrepeval huggingface dataset:
Sequence specificity in DNA for the interaction with adriamycin or daunomycin. (1982)

The interactions of adriamycin and daunomycin with various polydeoxyribonucleotides and some natural DNAs having different base pairs composition were studied by means of fluorimetric titrations. The quenching of the fluorescence occurring in the drugs complexed with polynucleotides and DNA is more efficiently induced by the C-G rich regions than by the A-T rich ones. By contrast, the affinity of the drugs for polynucleotides and DNAs in forming the molecular intercalated complexes is correlated mainly with the sequence of purines and pyrimidines in each strand of the duplex polymers, fairly independently of their nature. The regions having an alternate sequence of purines and pyrimidines in each strand are much more preferred than the regions having a continuous sequence; among the various alternate sequences, those having the structure of poly d(A-T) X poly d(A-T) appear to be a little more preferred than the others.
Prediction of creatinine clearance from serum creatinine concentration based on lean body mass (1981)

An equation for predicting endogenous creatinine clearance (CrCl) in adults and children (with both stable and unstable renal function) from serum creatinine concentration is presented. The predictions are compared with four other available estimating methods, bases on values in 110 subjects with renal impairment of widely differing degrees. In patients with stable and with unstable renal function the corelaion between measured and predicted CrCl was better with the new equation. In patients with rapid changing renal function the new equation resulted in accurate predictions CrCl within a few hours after the change, as opposed to several with the other methods. The elimination rate constant of the aminoglycoside antibiotic amikacin correlated more precisely with CrCl values estimated from the new equation that with those measured doing 24 hr or with the other prediction methods.
The PYRIN domain: A member of the death domain‐fold superfamily (2001)

PYRIN domains were identified recently as putative protein-protein interaction domains at the N-termini of several proteins thought to function in apoptotic and inflammatory signaling pathways. The approximately 95 residue PYRIN domains have no statistically significant sequence homology to proteins with known three-dimensional structure. Using secondary structure prediction and potential-based fold recognition methods, however, the PYRIN domain is predicted to be a member of the six-helix bundle death domain-fold superfamily that includes death domains (DDs), death effector domains (DEDs), and caspase recruitment domains (CARDs). Members of the death domain-fold superfamily are well established mediators of protein-protein interactions found in many proteins involved in apoptosis and inflammation, indicating further that the PYRIN domains serve a similar function. An homology model of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1, a member of the Apaf-1/Ced-4 family of proteins, was constructed using the three-dimensional structures of the FADD and p75 neurotrophin receptor DDs, and of the Apaf-1 and caspase-9 CARDs, as templates. Validation of the model using a variety of computational techniques indicates that the fold prediction is consistent with the sequence. Comparison of a circular dichroism spectrum of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1 with spectra of several proteins known to adopt the death domain-fold provides experimental support for the structure prediction.
Porous Hydroxyapatite Grafts in Chronic Subcrestal Periodontal Defects in Rhesus Monkeys: A Histological Investigation (1989)

The purpose of this investigation was to evaluate the histologic response to replamineform (porous) hydroxyapatite grafts in chronically inflamed, surgically created, periodontal pockets in Rhesus monkeys. Forty-eight subcrestal defects were surgically created in 8 Rhesus monkeys. Orthodontic wires were adapted to the base of the defects and left in place for 8 weeks. The defects were randomly assigned a treatment modality so that 8 granular porous and 8 block porous hydroxyapatite grafts were done. Eight sites were left as unoperated controls. Twenty-four contralateral sham-operated sites were treated by open curettage. Histometric measurements of the length of regenerated connective tissue attachment were recorded. Block hydroxyapatite, granular hydroxyapatite, and sham-operated sites exhibited similar amounts of regenerated connective tissue attachment, which was significantly greater than that which occurred in unoperated controls. Newly formed bone was observed within the porous channels of the hydroxyapatite grafts as well as in direct apposition on the surface of implant particles. New bone, cementum, and periodontal ligament was observed in grafted sites and in defects treated by open curettage. In some instances healing occurred by means of a long junctional epithelium. Histology confirmed that unoperated defects remained as unhealed, inflamed periodontal pockets. The results of this study suggest that porous hydroxyapatite grafts have the potential to regenerate the attachment apparatus in primates.
Fetal nigral grafts survive and mediate clinical benefit in a patient with Parkinson's disease (1998)

We have previously demonstrated that fetal nigral grafts can survive, reinnervate the striatum, and mediate clinically relevant recovery in a patient with Parkinson's disease (PD). Most previous autopsy cases have failed to identify meaningful numbers of viable grafted cells suggesting that differences in critical transplant variables determine graft viability. The present study evaluated the structural and functional correlates of fetal nigral transplantation in a second PD patient who received fetal nigral grafts according to our previously published transplant protocol. A 61-year-old woman with severe PD received bilateral fetal nigral grafts to the postcommissural putamen from seven donor fetuses (four right side and three left side) aged 6.5-9 weeks postconception. This patient died 19 months after surgery from a cause unrelated to the transplant surgery. Her postoperative clinical course was characterized by improved motor and activities of daily living scores during "off time," reduced "off time," and increased "on" time without dyskinesia. Positron emission tomography (PET) scans revealed a bilateral and progressive increase in fluorodopa (FD) uptake within the grafted putamen. Postmortem examination of the right hemisphere revealed large oval-shaped grafts containing more than 138,000 tyrosine-hydroxylase-immunoreactive (TH-ir) neurons. Grafted cells formed a seamless border with the host and provided dense TH-ir innervation to 78% of the host postcommissural putamen. Graft-mediated sprouting of host fibers was not observed. These data provide essential confirmation that, under appropriate transplant conditions, grafted nigral neurons can survive, reinnervate the host striatum, and provide clinical benefit to PD patients. These findings also support the concept that improved motor function and striatal FD uptake on PET after nigral grafting in PD are the result of the viability of grafted neurons and graft-derived reinnervation of the host striatum.
普通教科「情報」における情報倫理教育の位置づけ（第3報）―高校普通教科「情報」教科書分析を通して― (2003)

本研究は、高等学校に新たに平成15年度から必履修教科として設置される普通教科「情報」の指導において重要な意味を持つ情報倫理教育のあり方を探る基礎的な研究として、第1報、第2報で論じた中学生・高校生・大学生への情報倫理意識の実態調査と教育の実態の比較を行うため、現在発行されている全ての「情報」教科書の教育内容の比較を通して、学習者の意識と教科書における情報教育内容の特質を吟味しその内容特性について考察した。全ての教科書の記述内容の質的分析結果を横断的に比較整理し、その記述内容の特徴を論考した。そして高校生への調査との比較において教科書の実態分析をふまえた高等学校の普通教科「情報」における情報倫理教育の方向性について提言した。
Fluconazole-Resistant Candida auris Is Susceptible to Salivary Histatin 5 Killing and to Intrinsic Host Defenses (2017)

<i>Candida auris</i> is a newly identified species causing invasive candidemia and candidiasis. It has broad multidrug resistance (MDR) not observed for other pathogenic <i>Candida</i> species. Histatin 5 (Hst 5) is a well-studied salivary cationic peptide with significant antifungal activity against <i>Candida albicans</i> and is an attractive candidate for treating MDR fungi, since antimicrobial peptides induce minimal drug resistance. We investigated the susceptibility of <i>C. auris</i> to Hst 5 and neutrophils, two first-line innate defenses in the human host. The majority of <i>C. auris</i> clinical isolates, including fluconazole-resistant strains, were highly sensitive to Hst 5: 55 to 90% of cells were killed by use of 7.5 μM Hst 5. Hst 5 was translocated to the cytosol and vacuole in <i>C. auris</i> cells; such translocation is required for the killing of <i>C. albicans</i> by Hst 5. The inverse relationship between fluconazole resistance and Hst 5 killing suggests different cellular targets for Hst 5 than for fluconazole. <i>C. auris</i> showed higher tolerance to oxidative stress than <i>C. albicans</i>, and higher survival within neutrophils, which correlated with resistance to oxidative stress <i>in vitro</i> Thus, resistance to reactive oxygen species (ROS) is likely one, though not the only, important factor in the killing of <i>C. auris</i> by neutrophils. Hst 5 has broad and potent candidacidal activity, enabling it to combat MDR <i>C. auris</i> strains effectively.
Ordered stretching of single molecules of deoxyribose nucleic acid between microfabricated polystyrene lines (2001)

A technique for creating arrays of parallel, stretched single molecules of deoxyribose nucleic acid (DNA) on an arbitrary substrate for high-resolution scanning-probe imaging is discussed. The technique consists of lithographically patterning polystyrene lines on a substrate which then provide attachment sites for the ends of individual DNA molecules. Molecular combing is performed to stretch DNA from one polystyrene line to the other. Scanning-tunneling and atomic-force microscope images of single molecules of bacteriophage-lambda DNA are shown to demonstrate the advantages of this technique. Several applications, from high-resolution genomics to molecular electronics, are discussed.
(-)-Stepholidine antagonizes the inhibition by D2 receptor agonists on synaptosomal tyrosine hydroylase in rat corpus striatum. (1995)

The negative feedback regulation of presynaptic DA receptors is mediated via D2 receptors and SPD is an antagonist on presynaptic D2 DA receptors.
Effect of subinhibitory concentrations of vancomycin, cefazolin, ofloxacin, L-ofloxacin and D-ofloxacin on adherence to intravascular catheters and biofilm formation by Staphylococcus epidermidis (1998)

Staphylococcus epidermidis is the preeminent cause of nosocomial bacteraemia and infection of prosthetic medical devices. Bacterial adherence to biomaterial is a crucial early event in the pathogenesis of these infections. Antibiotics affect bacterial adherence to eukaryotic cells, capsule formation and biofilm production. However, results from studies involving coagulase-negative staphylococci are equivocal. In this study, the in-vitro adherence of radiolabelled bacteria was assayed to determine the effect of sublethal concentrations of a number of antibiotics on the attachment of four strains of S. epidermidis, with well-characterized adherence profiles, to intravascular catheters. The effect of antibiotics on biofilm production by S. epidermidis was assayed using a quantitative spectrophotometric assay. Although there was some strain-to-strain variability, none of the tested antibiotics affected bacterial attachment. However, treatment with cefazolin or vancomycin resulted in a significant decrease in biofilm elaboration. These data suggest that bacterial attachment by S. epidermidis, the initiating event associated with prosthetic device infection, cannot be prevented by subtherapeutic levels of fluoroquinolone, glycopeptide or beta-lactam antibiotics. However, later aggregative stages of adherence, associated with biofilm production, may be influenced by cell wall-active agents such as cefazolin and vancomycin.
Characterization of prion proteins with monospecific antisera to synthetic peptides. (1988)

The prion protein (PrP) 27-30 is the major macromolecular component in highly purified preparations of prions derived from scrapie-infected hamster brain. Immunoblotting studies demonstrated that this protein is generated by partial protease digestion of a larger precursor (PrPSc) with an apparent Mr of 33 to 35 kDa, and that a protease-sensitive cellular PrP isoform, designated PrPC, is present in normal hamster brain. To characterize the relationships among these proteins, ELISA and immunoblotting studies were undertaken with rabbit antisera raised against three synthetic PrP peptides. All three antisera were found to specifically react with the prion proteins, and failed to identify other lower or higher m.w. PrP proteins. Our results provide evidence that the primary structures of PrP 27-30, PrPSc, and PrPC are related; this conclusion supports molecular cloning studies indicating that these proteins are encoded by the same chromosomal gene.
Co-delivery of as-miR-21 and 5-FU by Poly(amidoamine) Dendrimer Attenuates Human Glioma Cell Growth in Vitro (2010)

MicroRNAs have been demonstrated to be deregulated in different types of cancer. miR-21 is a key player in the majority of cancers. Down-regulation of miR-21 in glioblastoma cells leads to repression of cell growth, increased cellular apoptosis and cell-cycle arrest, which can theoretically enhance the chemotherapeutic effect in cancer therapy. In this study, the poly(amidoamine) (PAMAM) dendrimer was employed as a carrier to co-deliver antisense-miR-21 oligonucleotide (as-miR-21) and 5-fluorouracil (5-FU) to achieve delivery of as-miR-21 to human glioblastoma cells and enhance the cytotoxicity of 5-FU antisense therapy. The inhibitory effect toward brain tumors was evaluated by MTT assay, and measurements of cell apoptosis and invasion using the human brain glioma cell line U251. PAMAM could be simultaneously loaded with 5-FU and as-miR-21, forming a complex smaller than 100 nm in diameter. Both the chemotherapeutant and as-miR-21 could be efficiently introduced into tumor cells. The co-delivery of as-miR-21 significantly improved the cytotoxicity of 5-FU and dramatically increased the apoptosis of U251 cells, while the migration ability of the tumor cells was decreased. These results suggest that our co-delivery system may have important clinical applications in the treatment of miR-21-overexpressing glioblastoma.
A 97.8% Efficient GaN HEMT Boost Converter With 300-W Output Power at 1 MHz (2008)

A 175-to-350 V hard-switched boost converter was constructed using a high-voltage GaN high-electron-mobility transistor grown on SiC substrate. The high speed and low on-resistance of the wide-band-gap device enabled extremely fast switching transients and low losses, resulting in a high conversion efficiency of 97.8% with 300-W output power at 1 MHz. The maximum efficiency was 98.0% at 214-W output power, well exceeding the state of the art of Si-based converters at similar frequencies.
Stem cell factor and c-kit in the mammalian testis: lessons originating from Mother Nature's gene knockouts (1997)

Analysis of mice with naturally occurring mutation in the genes encoding the tyrosine kinase receptor protein, c-kit, and its ligand, stem cell factor (SCF), has implicated these proteins in testicular development and function because of the phenotype of these mice of reduced or absent fertility. Descriptive and functional studies have highlighted the involvement of these proteins in primordial germ cell migration and survival, and in spermatogonial proliferation, survival and adhesion. This review summarises the current knowledge regarding functions of c-kit and SCF in the testis and discusses the implications of information gleaned from other biological systems.
Murine DNA Cytosine-C5 Methyltransferase:  Pre-Steady- and Steady-State Kinetic Analysis with Regulatory DNA Sequences (1996)

We present the first description of KmDNA, KdDNA, Kcat, and Kmethylation for a mammalian DNA methyltransferase. Homogeneous, 190 000 MTDNA (cytosine-5-)-methyltransferase isolated from mouse erythroleukemia cells has turnover constants of 0.15-0.59 h-1 with single-stranded and unmethylated double-stranded oligonucleotides containing a single CpG dinucleotide. These substrates were designed to mimic DNA transcriptional cis elements previously reported to have cytosine C-5-methylated regulation. The rate-limiting step for these substrates is the methylation step itself. In contrast, hemimethylated double-stranded substrates show burst kinetics, consistent with a rapid methylation event (3 h-1) followed by a slower step which determines steady-state Kcat. Hemimethylated and unmethylated double-stranded DNA shows similar binding affinities; these results reveal the molecular basis for the enzyme's preference for hemimethylated DNA to be the methyl transfer step. Substrates with multiple recognition sites do not show burst kinetics and have turnover rate constants of 6 h-1. Catalytic turnover for the mammalian enzyme is thus approximately 10-fold slower than that for the related bacterial enzymes. Our combined results show quantitatively that one enzyme is certainly capable of both maintenance and de novo methylation and that maintenance of the genomic methylation pattern is preferred over the de novo establishment of new patterns. Direct comparison of the mammalian enzyme with the bacterial DNA cytosine-C5 methyltransferase, M.SssI, indicates dramatic differences in preferences for single-stranded, double-stranded, and hemimethylated double-stranded substrates. Moreover, the specificity hierarchy shown for the M.SssI is derived from very different changes in K(m) and catalysis than those observed for the mammalian DCMTase. These results demonstrate that the M.SssI, and perhaps other DNA cytosine methyltransferases from bacteria, is functionally dissimilar to the mammalian enzyme.
Protein Backbone Modification by Novel C.alpha.-C Side-Chain Scission (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtein Backbone Modification by Novel C.alpha.-C Side-Chain ScissionDarshan Ranganathan, Narendra K. Vaish, and Kavita ShahCite this: J. Am. Chem. Soc. 1994, 116, 15, 6545–6557Publication Date (Print):July 1, 1994Publication History Published online1 May 2002Published inissue 1 July 1994https://pubs.acs.org/doi/10.1021/ja00094a008https://doi.org/10.1021/ja00094a008research-articleACS PublicationsRequest reuse permissionsArticle Views977Altmetric-Citations32LEARN 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
A novel recognition motif for phosphatidylinositol 3-kinase binding mediates its association with the hepatocyte growth factor/scatter factor receptor. (1993)

The pleiotropic effects (mitogenesis, motogenesis, and morphogenesis) elicited by hepatocyte growth factor/scatter factor (HGF/SF) are mediated by the activation of the tyrosine kinase receptor encoded by the MET proto-oncogene. Following autophosphorylation, the receptor associates with the p85/110 phosphatidylinositol (PI) 3-kinase complex in vivo and in vitro. By a combination of two complementary approaches, competition with synthetic phosphopeptides and association with Tyr-Phe receptor mutants, we have identified Y-1349 and Y-1356 in the HGF/SF receptor as the binding sites for PI 3-kinase. Y-1349VHV and Y-1356VNV do not conform to the canonical consensus sequence YXXM for PI 3-kinase binding and thus define YVXV as a novel recognition motif. Y-1349 and Y-1356 are located within the C-terminal portion of the HGF/SF receptor and are phosphorylation sites. The affinity of the N- and C-terminal src homology region 2 (SH2) domains of p85 for the phosphopeptides including Y-1349 and Y-1356 is 2 orders of magnitude lower than that measured for Y-751 in the platelet-derived growth factor receptor binding site. However, the closely spaced duplication of the novel recognition motif in the native HGF/SF receptor may allow binding with both SH2 domains of p85, thus generating an efficient docking site for PI 3-kinase. In agreement with this model, we have observed that a phosphopeptide including both Y-1349 and Y-1356 activates PI 3-kinase in vitro.
Apoptosis by genetic engineering. (1994)

Apoptotic cell death is physiological. Malignant cells often escape programmed cell death. Many genes that promote (p53) or antagonize (bcl-2, fes) apoptosis have been recognized. Apoptosis promoter genes can be activated by growth factor or hormone withdrawal in growth factor- or hormone-dependent tumor cells. Malignant cells acquiring apoptosis-resistance, still can be killed by cytotoxic lymphocytes releasing lymphotoxins. This phenomenon gives further support to the therapeutic use of activated and expanded lymphocyte populations and/or apoptosis-inducing cytokines. Chemotherapeutic agents (esp. topoisomerase inhibitors) frequently kill tumor cells by activating programmed cell death (PCD). Biologicals and chemotherapeutics may synergize in evoking apoptosis. We propose the cloning of apoptotic genes and their transfer by transfection in vivo into tumor cells. While transfection of genes into tumor cells in vitro is widely practiced, the lack of proper technology for transfection in vivo and the unknown aspects of apoptotic cell death are recognized.
Point of Disconnect: Internet Traffic and the U.S. Communications Infrastructure (2007)

The public communications infrastructure in the United States is largely invisible to all but a few engineers and operations personnel. Were it visible as a road system, it would appear to be excellent in some places, but showing wear with potholes in others — heavily congested at many times and locations, and in need of massive investment and redesign to support new vehicle types. It is as if most of the drivers in the country rushed out and traded in their cars for massive 20-wheeled trucks, blocking and slowing traffic everywhere they went.
SHOX2 DNA Methylation is a Biomarker for the diagnosis of lung cancer based on bronchial aspirates (2010)

Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.