gebhart/patrepeval huggingface dataset:
A new nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxyl]methyl]guanine, highly active in vitro against herpes simplex virus types 1 and 2 (1982)

A novel nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]-guanine (BIOLF-62), was found to have potent antiviral activity against herpes simplex virus types 1 and 2 at concentrations well below cytotoxic levels. For example, the Patton strain of herpes simplex virus type 1 was susceptible at concentrations 140- to 2,900-fold below that which inhibited cell division by 50%, depending upon the cell line used for assay. Different herpesvirus strains varied considerably in their susceptibility to the drug, as did results obtained with the same virus strain in different cell lines. BIOLF-62 compared favorably with 5-iodo-2'-deoxyuridine and acyclovir with respect to ratios of viral to cell inhibitory drug concentrations. Patterns of drug resistance to herpesvirus mutants suggested that the primary mode of action of BIOLF-62 is different from that of known antiviral compounds. Human adenovirus type 2, varicella-zoster virus, and Epstein-Barr virus were inhibited by this drug but at concentrations within the cell inhibitory range. Vaccinia virus and human cytomegalovirus were not inhibited at high drug concentrations.
Drugs in type 2 diabetes: their properties and recommended use (2010)

Abstract There are now six classes of oral antidiabetic drugs and a new class of injectable GLP‐1 agonists in the drug therapy of type 2 diabetes, with metformin remaining the cornerstone of treatment. Our Drug review considers their mode of action, properties and recommended use, followed by sources of further information and an analysis of prescription data. Copyright © 2010 Wiley Interface Ltd
Bone marrow transplant in myelodysplastic syndromes: new technologies, same questions. (2004)

Myelodysplastic syndrome (MDS) comprises a heterogeneous group of hematologic disorders characterized by a clonal abnormality of hematopoietic stem cells that results in a varying degree of cytopenias and risk of transformation into acute leukemia. Only allogeneic transplant has been shown to cure this disease. However, high nonrelapse mortality rates limit the applicability of conventional allografts and, even in young patients, long-term disease control ranging from only 30% to 50% has been reported. Novel transplant regimens, availability of alternative donors, and busulfan targeting promise to increase transplant applicability and reduce nonrelapse mortality rates. However, high relapse rates in patients with high-risk disease limit the success of this procedure to the point that a definite advantage of allografting over standard therapy remains controversial. New agents being developed for MDS may have a potential impact on transplant outcomes. Therefore, design and implementation of clinical trials of transplant for MDS should be encouraged to improve the natural history of this disease.
An Opioid Antagonist for Postoperative Ileus (2001)

Postoperative ileus, a temporary impairment of gastrointestinal motility, occurs universally after major abdominal surgery. This condition exacerbates nausea and vomiting, delays oral feeding, increases postoperative pain, and prolongs hospitalization. Nearly 100 years ago, Cannon and Murphy1 demonstrated in dogs that opening the peritoneal cavity and manipulating the intestines resulted in a “striking” inhibition of contractile activity in the gastrointestinal tract.In people, typical postoperative ileus is generally followed by the restoration of motility in the stomach and small bowel within 24 hours; colonic function is recovered over a period of 48 to 72 hours.2,3 Gastrointestinal transit is modulated by . . .
Fabrication of Bi-(Pb)-Sr-Ca-Cu-O mono- and multifilamentary superconductors and improvement in critical current density (1989)

The Bi-(Pb)-Sr-Ca-Cu-O superconductor has been fabricated into tapes without sheathing and into multifilamentary wires and tapes with Ag sheathing. Metallurgical studies as well as measurements have been made for them. Tape specimens prepared by combination and repetition of cold work (or cold press) and sintering showed critical current density Jc as high as 5×103 A/cm2 at 77 K with good reproducibility and reliability, although these specimens are sufficiently thick (0.5–1.0 mm). (Generally, Jc at zero field is inversely proportional to thickness.) For these tape specimens (with Cu sheath), sintering and Jc measurement were performed after the Cu sheath was removed. X-ray analysis showed that most of these tape specimens consist purely of high-Tc phase (∼107 K). In these specimens, the c axis tends to align well. This c axis alignment as well as compacting effect may be a cause of the enhancement in Jc . On the other hand, the tape specimens cold-worked and sintered only once (not repeated) showed Jc as small as only 102 A/cm2 with the c axis showing no sign of alignment. A 1330-filament Bi-Pb-Sr-Ca-Cu-O wire with a Ag sheath has been successfully fabricated. This multifilamentary wire shows critical temperature Tc of ∼105 K. A multifilamentary tape specimen fabricated by a combination of cold work and sintering showed Jc of 1.05×103 A/cm2 at 77 K.
1:n 10G-PON overlay of GPON link using bidirectional raman amplifier (2014)

We describe a novel 1: n 10G-PON overlay of GPON system using 1: n splitter and a bidirectional 10G-PON optical amplifier. We experimentally demonstrate an n=8 10G-PON overlay of GPON link with the 20-km feeder fiber and 1:32-way splitter using a bidirectional discrete Raman amplifier.
Potent activity of the Hsp90 inhibitor ganetespib in prostate cancer cells irrespective of androgen receptor status or variant receptor expression (2012)

Androgen ablation therapy represents the first line of therapeutic intervention in men with advanced or recurrent prostate tumors. However, the incomplete efficacy and lack of durable response to this clinical strategy highlights an urgent need for alternative treatment options to improve patient outcomes. Targeting the molecular chaperone heat shock protein 90 (Hsp90) represents a potential avenue for therapeutic intervention as its inhibition results in the coordinate blockade of multiple oncogenic signaling pathways in cancer cells. Moreover, Hsp90 is essential for the stability and function of numerous client proteins, a number of which have been causally implicated in the pathogenesis of prostate cancer, including the androgen receptor (AR). Here, we examined the preclinical activity of ganetespib, a small molecule inhibitor of Hsp90, in a panel of prostate cancer cell lines. Ganetespib potently decreased viability in all lines, irrespective of their androgen sensitivity or receptor status, and more effectively than the ansamycin inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). Interestingly, while ganetespib exposure decreased AR expression and activation, the constitutively active V7 truncated isoform of the receptor was unaffected by Hsp90 inhibition. Mechanistically, ganetespib exerted concomitant effects on mitogenic and survival pathways, as well as direct modulation of cell cycle regulators, to induce growth arrest and apoptosis. Further, ganetespib displayed robust antitumor efficacy in both AR-negative and positive xenografts, including those derived from the 22Rv1 prostate cancer cell line that co-expresses full-length and variant receptors. Together these data suggest that further investigation of ganetespib as a new therapeutic treatment for prostate cancer patients is warranted.
ChemInform Abstract: Two Stereoisomeric Pentacyclic Oxindole Alkaloids from Uncaria tomentosa: Uncarine C (I) and Uncarine E (II) (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Blockade by polyamine NMDA antagonists related to ifenprodil of NMDA‐induced synthesis of cyclic GMP, increases in calcium and cytotoxicity in cultured neurones (1995)

1. Antagonists acting at the polyamine site of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, including a number of heterocyclic aminoalcohols related to ifenprodil, were investigated to establish their functional interaction at the NMDA receptor and their neuroprotective profile. 2. In murine cultured neocortical neurones, NMDA (100 microM)-stimulated production of guanosine 3':5'-cyclic monophosphate (cyclic GMP) was blocked by N-1([thienyl]-cyclohexyl)-piperidine (1 microM) and by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (100 microM). Ifenprodil and structurally related heterocyclic aminoalcohols inhibited in a concentration-dependent manner the NMDA-stimulated, NO-dependent production of cyclic GMP; rank potency order was: ifenprodil > 2309 BT > tibalosine > threo-tibalosine > 840S. 3. All of the polyamine NMDA antagonists blocked NMDA (300 microM)-stimulated increases in intracellular calcium concentrations as measured by changes in the fluorescence of pre-loaded fluo-3-acetoxy methyl ester. Rank potency order was: ifenprodil > 2309 BT > 840S > tibalosine > threo-tibalosine. 4. In a series of experiments to evaluate the effectiveness of the polyamine NMDA antagonists as blockers of NMDA-induced cytotoxicity, all of the drugs were found to inhibit the leakage of lactate dehydrogenase after the exposure of the murine neocortical cultures to NMDA (100 microM, 5 h). Rank potency order was: 2309 BT > ifenprodil > tibalosine > threo-tibalosine > 840S. 5. These results provide direct evidence that polyamine NMDA antagonists produce a functional blockade of the NMDA receptor complex. The heterocyclic amino alcohols described herein, likeifenprodil, block NMDA-mediated elevation of intracellular NO and calcium, two key events in the excitotoxic cascade, and are cytoprotective.
Molecular characterization and expression of an alfalfa protein with sequence similarity to mammalian ERp72, a glucose‐regulated endoplasmic reticulum protein containing active site sequences of protein disulphide isomerase (1992)

A complementary DNA clone (G1) containing sequence similarity to the mammalian lumenal endoplasmic reticulum protein ERp72 was isolated from an alfalfa (Medicago sativa L.) cDNA library by screening with a cDNA encoding human protein disulphide isomerase (PDI), which contains two thioredoxin-like active site regions which are highly conserved in ERp72. The polypeptide encoded by G1 consists of 364 amino acids, possesses a putative N-terminal secretory signal sequence and two regions, 113 amino acids apart, identical to the active sites of PDI and ERp72. G1 appears to be encoded by a small gene family in alfalfa, whose transcripts are constitutively expressed in all major organs of the plant. In alfalfa cell suspension cultures, G1 transcripts were markedly induced by treatment with tunicamycin, but not in response to calcium ionophore, heat shock or fungal elicitor. A similar expression pattern was observed for transcripts encoded by B2, a recently cloned alfalfa cDNA with strong sequence similarity to PDI. We discuss potential roles of plant proteins resembling vertebrate PDI and ERp72.
Organ Hypertrophic Signaling within Caveolae Membrane Subdomains Triggered by Ouabain and Antagonized by PST 2238 (2004)

In addition to inhibition of the Na-K ATPase, ouabain activates a signal transduction function, triggering growth and proliferation of cultured cells even at nanomolar concentrations. An isomer of ouabain (EO) circulates in mammalians at subnanomolar concentrations, and increased levels are associated with cardiac hypertrophy and hypertension. We present here a study of cardiac and renal hypertrophy induced by ouabain infused into rats for prolonged periods and relate this effect to the recently described ouabain-induced activation of the Src-EGFr-ERK signaling pathway. Ouabain infusion into rats (15 microg/kg/day for 18 weeks) doubled plasma ouabain levels from 0.3 to 0.7 nm and increased blood pressure by 20 mm Hg (p < 0.001), cardiac left ventricle (+11%, p < 0.05), and kidney weight (+9%, p < 0.01). These effects in vivo are associated with a significant enrichment of alpha1, beta1, gammaa Na-K ATPase subunits together with Src and EGFr in isolated renal caveolae membranes and activation of ERK1/2. In caveolae, direct Na-K ATPase/Src interactions can be demonstrated by co-immunoprecipitation. The interaction is amplified by ouabain, at a high affinity binding site, detectable in caveolae but not in total rat renal membranes. The high affinity site for ouabain is associated with Src-dependent tyrosine phosphorylation of rat alpha1 Na-K ATPase. The antihypertensive compound, PST 2238, antagonized all ouabain-induced effects at 10 microg/kg/day in vivo or 10(-10)-10(-8) m in vitro. These findings provide a molecular mechanism for the in vivo pro-hypertrophic and hypertensinogenic activity of ouabain, or by analogy those of EO in humans. They also explain the pharmacological basis for PST 2238 treatment.
Highly Porous Polymer Matrices as a Three-Dimensional Culture System for Hepatocytes (1997)

Hepatocyte-based therapies (e.g., hepatocyte transplantation and extracorporeal support devices) may provide alternative therapies to treat patients with liver disease, but suitable approaches to localize these cells to a given location while maintaining liver-specific gene expression must be developed. The suitability of highly porous three-dimensional sponges fabricated from poly (l-lactic acid) [PLLA] as an hepatocyte culture system was evaluated in this study. Sponges were fabricated utilizing a particulate leaching technique, and were approximately 95% porous, with an average pore diameter of 180 μm. Hepatocytes seeded into these sponges adhered and remained viable for 14 days. However, the secretion rate of albumin from these cells, an indication of liver-specific gene expression, was low (approximately 6 pg/cell/day at day 1), and decreased steadily over the 14 days of the experiment. Coating sponges with collagen, and more preferably, immobilizing cells within the PLLA sponges with a collagen gel, led to enhanced cell survival and albumin secretion at all time points. These data suggest that porous PLLA sponges may provide a novel system for long-term culture of hepatocytes, and proper design of the system may allow the liver-specific gene expression of hepatocytes transplanted in these matrices to be enhanced.
Recombinant Adeno-Associated Virus Serotype 6 (rAAV2/6)-Mediated Gene Transfer to Nociceptive Neurons through Different Routes of Delivery (2009)

We have found that rAAV2/6 is an efficient vector to deliver transgenes to nociceptive neurons in mice. Furthermore, the characterization of the transduction profile may facilitate gene transfer studies to dissect mechanisms behind neuropathic pain.
Purification and biochemical properties of tumor-associated transplantation antigens from methylcholanthrene-induced murine sarcomas. (1982)

A tumor-associated transplantation antigen with an apparent molecular weight of 75,000 has been isolated from the cytosol of the BALB/c methylcholanthrene-induced sarcoma, Meth A. The antigen was purified either by preparative electrophoresis in the presence of NaDodSO4 or by immunoaffinity chromatography after hexylamine agarose chromatography, gel filtration, and hydroxylapatite chromatography. The 75-kilodalton (kDal) protein prepared by either of these methods effectively primed BALB/c mice to reject the Meth A tumor; such priming provided no protection against challenge by other independently derived sarcomas of BALB/c origin. A second protein, also 75 kDal, was isolated from the cytosol of the recently derived methylcholanthrene-induced sarcoma CI-4 by essentially the same chromatographic scheme. This protein also was immunogenic in the tumor rejection assay and provided protection only against CI-4 challenge. The antigens purified from the Meth A and CI-4 sarcomas appear to be closely related proteins. Both of them can be purified from the cytosol fraction and can be recognized by a rabbit antiserum prepared against the Meth A 75-kDal protein. The two proteins have approximately the same molecular weight, have similar but not identical amino acid compositions, and differ in their chromatographic behavior on hexylamine agarose and hydroxylapatite as well as in their isoelectric points. These results indicate that the individually specific transplantation antigens found in chemically induced sarcomas may be the products of a single multigene family or somatic derivatives of a single gene.
Synthesis of .beta.-resorcylic macrolides via organopalladium chemistry. Application to the total synthesis of (S)-zearalenone (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of .beta.-resorcylic macrolides via organopalladium chemistry. Application to the total synthesis of (S)-zearalenoneA. Kalivretenos, J. K. Stille, and L. S. HegedusCite this: J. Org. Chem. 1991, 56, 8, 2883–2894Publication Date (Print):April 1, 1991Publication History Published online1 May 2002Published inissue 1 April 1991https://pubs.acs.org/doi/10.1021/jo00008a053https://doi.org/10.1021/jo00008a053research-articleACS PublicationsRequest reuse permissionsArticle Views1894Altmetric-Citations110LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Learning Multiple Layers of Features from Tiny Images (2024)

April 8, 2009Groups at MIT and NYU have collected a dataset of millions of tiny colour images from the web. It is, in principle, an excellent dataset for unsupervised training of deep generative models, but previous researchers who have tried this have found it di cult to learn a good set of lters from the images. We show how to train a multi-layer generative model that learns to extract meaningful features which resemble those found in the human visual cortex. Using a novel parallelization algorithm to distribute the work among multiple machines connected on a network, we show how training such a model can be done in reasonable time. A second problematic aspect of the tiny images dataset is that there are no reliable class labels which makes it hard to use for object recognition experiments. We created two sets of reliable labels. The CIFAR-10 set has 6000 examples of each of 10 classes and the CIFAR-100 set has 600 examples of each of 100 non-overlapping classes. Using these labels, we show that object recognition is signi cantly
New assertion concepts for self-metric software validation (1975)

Automated tools and structured programming techniques are in use on a variety of scientific and business application programming projects within the McDonnell Douglas Corporation. An examination of the resulting programs reveals certain development and maintenance characteristics that suggest new and very interesting applications for automated tools. An extension of PET (a currently operational McDonnell Douglas validation tool for FORTRAN) to include a user embedded assertion capability offers a step in the direction of automatically verifying the dynamic execution of programs. A user-oriented local and global assertion capability is introduced and its implementation is discussed. Application of these tools within a well-conceived structured programming environment offers a positive step forward in the development of more reliable software systems.
Prolonged Absence of Mechanoluminal Stimulation in Human Intestine Alters the Transcriptome and Intestinal Stem Cell Niche (2017)

Even with sufficient systemic caloric intake, human ileum responds to the chronic absence of mechanoluminal stimulation by up-regulating brush-border enzymes, transporters, structural genes, and ISC genes <i>LGR5</i> and <i>ASCL2</i>. These data suggest that unfed intestine is primed to replenish the ISC population upon re-introduction of enteral feeding. Therefore, the elucidation of pathways involved in these processes may provide therapeutic targets for patients with intestinal failure. RNA sequencing data are available at Gene Expression Omnibus series GSE82147.
Circular Oligonucleotides: New Concepts in Oligonucleotide Design (1996)

Recent progress in the synthesis and properties of circular oligonucleotides as ligands for DNA and RNA and as templates for polymerase enzymes is described. Small synthetic circular DNAs, RNAs, and chimeric analogues ranging from 28 to 74 nucleotides in size have been synthesized with the use of nonenzymatic ligation strategy. Some of these were designed to undergo triplex formation with single-stranded DNA and RNA targets, and many bind with affinities and sequence selectivities considerably greater than those seen for linear oligonucleotides. Design strategies and modes of binding are discussed in the light of possible use of such molecules as hybridization probes, molecular diagnostics, and sequence-specific inhibitors of gene expression. Small circular oligonucleotides have also been shown to act as unusually efficient templates for DNA and RNA polymerases, which produce long, repeating copies of the circular sequence by a rolling circle process.
Orientation insensitive power transfer by magnetic resonance for mobile devices (2013)

The efficiency of wireless power transfer (WPT) from an orientation insensitive system to a mobile device by strongly coupled magnetic resonance (SCMR) is reported here. This paper compares an optimal loop-based design in standard SCMR systems with misalignment insensitive system (3D and 3loop structure), which exhibits higher efficiency than typical SCMR devices in several directions in a sphere.
Resetting proteostasis with ISRIB prevents pulmonary fibrosis (2020)

Abstract Aging is among the most important risk factors for the development of pulmonary fibrosis. We found that a small molecule that specifically inhibits translational inhibition induced by activation of the integrated stress response (ISRIB) attenuated the severity of pulmonary fibrosis in young and old mice. The more severe fibrosis in old compared to young mice was associated with increased recruitment of pathogenic monocyte-derived alveolar macrophages. Using genetic lineage tracing and transcriptomic profiling we found that ISRIB modulates stress response signaling in alveolar epithelial cells resulting in decreased apoptosis and decreased recruitment of pathogenic monocyte-derived alveolar macrophages. These data support multicellular model of fibrosis involving epithelial cells, pathogenic monocyte-derived alveolar macrophages and fibroblasts. Inhibition of the integrated stress response in the aging lung epithelium ameliorates pulmonary fibrosis by preventing the prolonged recruitment of monocyte-derived alveolar macrophages.