gebhart/patrepeval huggingface dataset:
Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs (2015)

Two decades after the discovery of the first animal microRNA (miRNA), the number of miRNAs in animal genomes remains a vexing question. Here, we report findings from analyzing 1,323 short RNA sequencing samples (RNA-seq) from 13 different human tissue types. Using stringent thresholding criteria, we identified 3,707 statistically significant novel mature miRNAs at a false discovery rate of ≤ 0.05 arising from 3,494 novel precursors; 91.5% of these novel miRNAs were identified independently in 10 or more of the processed samples. Analysis of these novel miRNAs revealed tissue-specific dependencies and a commensurate low Jaccard similarity index in intertissue comparisons. Of these novel miRNAs, 1,657 (45%) were identified in 43 datasets that were generated by cross-linking followed by Argonaute immunoprecipitation and sequencing (Ago CLIP-seq) and represented 3 of the 13 tissues, indicating that these miRNAs are active in the RNA interference pathway. Moreover, experimental investigation through stem-loop PCR of a random collection of newly discovered miRNAs in 12 cell lines representing 5 tissues confirmed their presence and tissue dependence. Among the newly identified miRNAs are many novel miRNA clusters, new members of known miRNA clusters, previously unreported products from uncharacterized arms of miRNA precursors, and previously unrecognized paralogues of functionally important miRNA families (e.g., miR-15/107). Examination of the sequence conservation across vertebrate and invertebrate organisms showed 56.7% of the newly discovered miRNAs to be human-specific whereas the majority (94.4%) are primate lineage-specific. Our findings suggest that the repertoire of human miRNAs is far more extensive than currently represented by public repositories and that there is a significant number of lineage- and/or tissue-specific miRNAs that are uncharacterized.
Activation of NLRX1 by NX-13 Alleviates Inflammatory Bowel Disease through Immunometabolic Mechanisms in CD4+ T Cells (2019)

Inflammatory bowel disease (IBD) is a complex autoimmune disease with dysfunction in pattern-recognition responses, including within the NLR family. Nucleotide-binding oligomerization domain, leucine rich repeat containing X1 (NLRX1) is a unique NLR with regulatory and anti-inflammatory functions resulting in protection from IBD in mouse models. NX-13 is an orally active, gut-restricted novel drug candidate that selectively targets and activates the NLRX1 pathway locally in the gut. In vitro and in vivo efficacy of NLRX1 activation by NX-13 was examined. Oral treatment with NX-13 alleviates disease severity, colonic leukocytic infiltration, and cytokine markers of inflammation in three mouse models of IBD (dextran sulfate sodium, Mdr1a<sup>-/-</sup>, and CD45RB<sup>hi</sup> adoptive transfer). Treatment of naive CD4<sup>+</sup> T cells with NX-13 in vitro decreases differentiation into Th1 and Th17 subsets with increased oxidative phosphorylation and decreased NF-κB activation and reactive oxygen species. With stimulation by PMA/ionomycin, TNF-α, or H<sub>2</sub>O<sub>2</sub>, PBMCs from ulcerative colitis patients treated with NX-13 had decreased NF-κB activity, TNF-α<sup>+</sup> and IFN-γ<sup>+</sup> CD4<sup>+</sup> T cells and overall production of IL-6, MCP1, and IL-8. NX-13 activates NLRX1 to mediate a resistance to both inflammatory signaling and oxidative stress in mouse models and human primary cells from ulcerative colitis patients with effects on NF-κB activity and oxidative phosphorylation. NX-13 is a promising oral, gut-restricted NLRX1 agonist for treating IBD.
Inhibitors of the Lipid Phosphatase SHIP2 Discovered by High Throughput Affinity Selection-Mass Spectrometry Screening of Combinatorial Libraries (2009)

This manuscript describes the discovery and characterization of inhibitors of the lipid phosphatase SHIP2, an important target for the treatment of Type 2 diabetes, using the Automated Ligand Identification System. ALIS is an affinity selection-mass spectrometry platform for label-free, high throughput screening of mixture-based combinatorial libraries. We detail the mass-encoded synthesis of a library that yielded NGD-61338, a pyrazole-based SHIP2 inhibitor. Quantitative ALIS affinity measurements and inhibition of SHIP2 enzymatic activity indicate that this compound has micromolar binding affinity and inhibitory activity for this target. This inhibitor, which does not contain a phosphatase "warhead," binds the active site of SHIP2 as determined by ALIS-based competition experiments with the enzyme's natural substrate, phosphatidylinositol 3,4,5-triphosphate (PIP3). Structure-activity relationships for NGD-61338 and two other ligand classes discovered by ALIS screening were explored using a combination of combinatorial library synthesis and ALIS-enabled affinity ranking in compound mixtures.
A novel force microscope and point contact probe (1993)

The mechanical properties of very small volumes of material can vary greatly from bulk properties. These modified properties are of interest in many areas including the operation of atomic force microscopy (AFM), the study of adhesion and fracture, and the evaluation of electrical contact response. Despite the importance of these properties, AFM has not yet been successfully utilized for their investigation. Most existing AFMs still rely on the control and monitoring of displacements, with forces being inferred from spring constants. This would be fine if other interactions, such as those between the tip and the surface, were minor perturbations. However, this is frequently not the case, particularly for contact mode AFM. Hence very little is known about the forces applied in the contact and their affect on both the tip and the sample. In this article we describe an AFM probe where forces rather than displacements are applied to the tip. This allows absolute determination of contact compliance and hence provides a measure of the tip–surface interaction. As an example of its use we show quantitatively the effect of the adsorbed water and meniscus forces present in ambient probe microscopy.
Effect of catalyst film thickness on carbon nanotube growth by selective area chemical vapor deposition (2001)

The correlation between prepatterned catalyst film thickness and carbon nanotube (CNT) growth by selective area chemical vapor deposition (CVD) was studied using Fe and Ni as catalyst. To eliminate sample-to-sample variations and create a growth environment in which the film thickness is the sole variable, samples with continuously changing catalyst film thickness from 0 to 60 nm were fabricated by electron-gun evaporation. Using thermal CVD CNTs preferentially grow as a dense mat on the thin regions of the catalyst film. Moreover, beyond a certain critical film thickness no tubes were observed. The critical film thickness for CNT growth was found to increase with substrate temperature. There appears to be no strong correlation between the film thickness and the diameter of the tubes. In contrast, using plasma enhanced CVD with Ni as catalyst, vertically oriented CNTs grow in the entire range of catalyst film thickness. The diameter of these CNTs shows a strong correlation with the catalyst film thickness. The significance of these experimental trends is discussed within the framework of the diffusion model for CNT growth.
Propagation of genetically altered tumor cells derived from fine-needle aspirates of primary breast carcinoma. (1998)

Because primary breast tumors are diagnosed earlier in the clinic, procurement of sufficient amounts of tumor tissue for in-depth biological characterization is becoming increasingly difficult. We demonstrate here that relatively small numbers of tumor cells within samples of fine-needle aspirates (FNA) can be propagated in culture. Of 25 cases attempted, 12 were passageable, resulting in up to 10(7) viable cells. FNA-derived cultures were evaluated for anchorage-independence, c-erb-B2 overexpression, aneusomy, and pattern of allelic loss. In every case examined, the cultured cells closely resembled the original tumor tissue and displayed one or more tumor phenotypes. The incidence of erb-B2 overexpressing tumors was similar in passageable and nonpassageable cases (33% versus 31%, respectively). FNAs that are expanded from a wide range of clinical breast material could be useful for functional studies presently limited to rare established cell lines, such as aberrant signal transduction and gene regulation, and for testing potential anticancer vaccines and drugs.
Perinatal programming, renal development, and adult renal function*1 (2002)

Substantial data indicate that maternal diet during gestation, as well as perinatal events, affect organogenesis and, furthermore, may affect organ function at maturity, thus determining whether an individual is prone or resistant to a variety of health problems such as hypertension, cardiovascular disease, or renal dysfunction. This concept is called perinatal programming, or the fetal origins of adult disease (FOAD), a concept that arose after the publication of epidemiologic observations by Barker and colleagues that birth weight among apparently normal individuals studied in midlife was inversely associated with the presence of cardiovascular disease and hypertension. We now review evidence from studies in experimental animal models that have used nutritional and pharmacologic manipulation to extend epidemiologic observations.
Learning Spread-out Local Feature Descriptors (2017)

We propose a simple, yet powerful regularization technique that can be used to significantly improve both the pairwise and triplet losses in learning local feature descriptors. The idea is that in order to fully utilize the expressive power of the descriptor space, good local feature descriptors should be sufficiently "spread-out" over the space. In this work, we propose a regularization term to maximize the spread in feature descriptor inspired by the property of uniform distribution. We show that the proposed regularization with triplet loss outperforms existing Euclidean distance based descriptor learning techniques by a large margin. As an extension, the proposed regularization technique can also be used to improve image-level deep feature embedding.
Vision in bad weather (1999)

Current vision systems are designed to perform in clear weather. Needless to say, in any outdoor application, there is no escape from "bad" weather. Ultimately, computer vision systems must include mechanisms that enable them to function (even if somewhat less reliably) in the presence of haze, fog, rain, hail and snow. We begin by studying the visual manifestations of different weather conditions. For this, we draw on what is already known about atmospheric optics. Next, we identify effects caused by bad weather that can be turned to our advantage. Since the atmosphere modulates the information carried from a scene point to the observer it can be viewed as a mechanism of visual information coding. Based on this observation, we develop models and methods for recovering pertinent scene properties, such as three-dimensional structure, from images taken under poor weather conditions.
Effect of the microbial lactase (EC 3.2.1.23) activity in yoghurt on the intestinal absorption of lactose: An in vivo study in lactase-deficient humans (1990)

Breath hydrogen excretion was measured in eight lactase (EC 3.2.1.108)-deficient volunteers ingesting 18 g lactose in the form of milk, yoghurt and heated yoghurt. Total excess hydrogen excretion (area under curve) was significantly lower after yoghurt and heated yoghurt, than after milk: 103 (SE 29), 191 (SE 32), and 439 (SE 69) respectively (P less than 0.001). The oro-caecal transit time of fermentable components from yoghurt and heated yoghurt (mainly lactose) was longer than that from milk: 165 (SE 17), 206 (SE 19), v. 103 (SE 19) min (P less than 0.01). An intestinal perfusion technique was used in the same subjects after ingestion on two consecutive days of 18 g lactose in yoghurt and heated yoghurt. Significantly less lactose was recovered from the terminal ileum after yoghurt than after heated yoghurt meals: 1740 (SE 260) v. 2825 (SE 461) mg (P less than 0.05), and approximately one-fifth of the lactase activity contained in yoghurt reached the terminal ileum. These findings indicate that more than 90% of the lactose in yoghurt is digested in the small intestine of lactase-deficient subjects and suggest that both the lactase activity contained in the viable starter culture and a slow oro-caecal transit time are responsible for this excellent absorption.
Tratamiento preventivo en el pie diabético (2002)

espanolEste articulo muestra la clasificacion del pie diabetico en seis grupos. Esta clasificacion se lleva a cabo despues de la exploracion de los llamados factores de riesgo en este tipo de pacientes. Una vez conocemos a que grupo incluimos ese pie, determinamos nuestra actuacion preventiva, con el fin de evitar la amputacion parcial o total del mismo. Los factores de riesgo son los siguientes: neuropatia, angiopatia, morfologia del pie, queratopatias y edema. Despues de realizar la exploracion y observar o no la presencia de los factores de riesgo clasificamos el pie en: Grupo 1: el pie diabetico no tiene de ulceracion; Grupo 2: los factores de riesgo estan presentes; Grupo 3: existencia de ulceracion; Grupo 4: la infeccion retrasa la curacion y puede destruir los tejidos; Grupo 5: la necrosis es el resultado de la destruccion del tejido a partir de la infeccion y la isquemia; Grupo 6: aparicion de osteitis extensa, la amputacion es inevitable. EnglishThis report shows a classification of the diabetic foot into six stages. This staging system is realized after the professional explores risk factors of this kind of patients. Once we know the stage, we determinate our preventive management,with the purpose of avoiding total or partial foot amputation. Risk factors are: neuropathy, ischaemia, foot morphology, keratotic lesions and edema. After the exploration has been realized and the presence or absence of risk factors has been noticed, the foot is classified into: Stage 1: The diabetic foot may have no risk factor for ulceration; Stage 2: Risk factors are present; Stage 3: Ulceration exists; Stage 4: Infection delays healing and may damage tissues; Stage 5: Necrosis is the outcome of tissue destruction starting from infection and ischaemia; Stage 6: Extensive osteomyelitis is present, the amputation is inevitable.
The triple combination of tenofovir, emtricitabine and efavirenz shows synergistic anti-HIV-1 activity in vitro: a mechanism of action study (2009)

This study demonstrated a clear correlation between the synergistic antiviral activities of TFV+FTC, TFV+EFV, FTC+EFV, and TFV+FTC+EFV combinations and synergistic HIV-1 RT inhibition at the enzymatic level. We propose the molecular mechanisms for the TFV+FTC+EFV synergy to be a combination of increased levels of the active metabolites TFV-DP and FTC-TP and enhanced DEC formation by a chain-terminated DNA and HIV-1 RT in the presence of the second and the third drug in the combination. This study furthers the understanding of the longstanding observations of synergistic anti-HIV-1 effects of many NRTI+NNRTI and certain NRTI+NRTI combinations in cell culture, and provides biochemical evidence that combinations of anti-HIV agents can increase the intracellular drug efficacy, without increasing the extracellular drug concentrations.
Assembly of Colloidal Crystals at Electrode Interfaces (1997)

We describe a theory for a new type of colloid behavior whereby particles deposited on a surface by electrophoresis are manipulated to form two-dimensional crystals. Since the particles are equally charged, the clustering is opposite that expected from electrostatic considerations. Such behavior is consistent with migration due to electrohydrodynamic flows associated with polarization layers and ion currents. Provided colloid stability is maintained, the assembly processes take place with both dc and ac fields and may be modulated by adjusting the field strength or frequency. No migration is present at frequencies above 1 MHz. Two-dimensional fluid and crystalline states can be formed on the electrode surface. Experiments with patterned electrodes demonstrate the presence of the electrohydrodynamic flow. A mathematical model of the electrohydrodynamics provides insight into the assembly process.
List of Icons (2012)

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Cause of Death in Follicular Lymphoma in the First Decade of the Rituximab Era: A Pooled Analysis of French and US Cohorts (2018)

Despite the improvement in overall survival in patients with FL in the rituximab era, their leading COD remains lymphoma, especially after disease transformation. Treatment-related mortality also represents a concern, which supports the need for less-toxic therapies.
Novel Modification of 5-Formyluracil by Cysteine Derivatives in Aqueous Solution (1998)

Reactivities of 5-formyl-2'-deoxyuridine (fdU) and its 5'-monophosphate (fdUMP) to amino acids, amines and thiol compounds in neutral aqueous solution have been studied to elucidate the postmodification of the 5-formyluracil (fU) moiety in cells. fdU and fdUMP specifically reacted with cysteine and its analogs to form thiazolidine derivatives. The reaction involved condensation of the formyl group of fU with both alpha-NH2 (or NH2 at the equivalent position) and SH groups of cysteine derivatives.
Sample immobilization protocols for matrix‐asssisted laser‐desorption mass spectrometry (1992)

Methods are described for the purification of proteins prior to analysis by matrix-assisted laser-desorption mass spectrometry. Contaminated protein samples were immobilized onto the surfaces of sample targets and rinsed. In general, a layer of electrosprayed nitrocellulose gave better results than the roughened gold surface of an untreated target. Using this approach, spectra could be obtained from low picomole quantities of protein in the presence of contaminants which did not inhibit the binding of the protein to the substrate.
ISO 9000 for Building and Civil Engineering Contractors (1998)

Quality assurance has been widely adopted by the construction sectors in Hong Kong since the introduction of ISO 9000 quality standards in 1987. Over 100 building and Civil engineering contractors have successfully achieved ISO 9000 certification in Hong Kong but a vigorous debate still continues on how appropriate ISO 9000 is to the construction Industry. The ISO 9000 was initially developed with the manufacturing industry in mind and may not be totally suitable for the construction Industry. A survey has been conducted on certified contractors to collect objective and representative evidence of the practicability of applying ISO 9000. This paper reveals their motivation for and experience in impiementing a quality management system to ISO 9000. The benefits of the ISO 9000 quality system on construction companies and the inter-relationship between quality, cost and time are also discussed.
ChemInform Abstract: A Water‐Stable Gadolinium(III) Complex Derived from a New Pentadentate “Expanded Porphyrin” Ligand. (1989)

Abstract The general lanthanoid‐binding properties of new monoanionic porphyrin‐like ligands are explored.
Pharmacological characterization of the human histamine H2receptor stably expressed in Chinese hamster ovary cells (1994)

1. The gene for the human histamine H2 receptor was stably expressed in Chinese hamster ovary (CHO) cells and characterized by [125I]-iodoaminopotentidine binding studies. In addition, the coupling of the expressed receptor protein to a variety of signal transduction pathways was investigated. 2. After cotransfection of CHO cells with pCMVhumH2 and pUT626, a phleomycine-resistant clonal cell line (CHOhumH2) was isolated that expressed 565 +/- 35 fmol kg-1 protein binding sites with high affinity (0.21 +/- 0.02 nM) for the H2 antagonist, [125I]-iodoaminopotentidine. 3. Displacement studies with a variety of H2 antagonists indicated that the encoded protein was indistinguishable from the H2 receptor identified in human brain membranes and guinea-pig right atrium. The Ki-values observed in the various preparations correlated very well (r2 = 0.996-0.920). 4. Displacement studies with histamine showed that a limited fraction (32 +/- 6%) of the binding sites showed a high affinity for histamine (2 +/- 1.2 microM); the shallow displacement curves were reflected by a Hill-coefficient significantly different from unity (nH = 0.58 +/- 0.09). The addition of 100 microM Gpp(NH)p resulted in a steepening of the displacement curve (nH = 0.79 +/- 0.02) and a loss of high affinity sites for histamine. 5. Displacement studies with other agonists indicated that the recently developed specific H2 agonists, amthamine and amselamine, showed an approximately 4-5 fold higher affinity for the human H2 receptor than histamine. 6. Stimulation of CHOhumH2 cells with histamine resulted in a rapid rise of the intracellular cyclic AMP levels. After 10 min an approximately 10 fold increase in cyclic AMP could be measured. TheEC50 value for this response was 7 +/- 1 nM for histamine. This response was effectively blocked by tiotidine and cimetidine, resulting in Ki values of 8 +/- 1 nM and 0.56 +/- 0.24 MicroM respectively.7. Stimulation of CHOhumH2 cells with histamine neither inhibited the A23187-induced release of[3H]-arachidonic acid nor changed the intracellular IP3 levels.8. These results show that the cloned human gene encodes a histamine H2 receptor that is indistinguishable from the H2 receptor identified in human brain tissue. This receptor is functionally coupled to the adenylate cyclase in CHO cells, but does not influence the inositolphosphate turnover or arachidonic acid release.
Lithium tris(3-ethyl-3-pentyloxy)aluminohydride. A new remarkably chemoselective reagent for the reduction of aldehydes in the presence of ketones (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLithium tris(3-ethyl-3-pentyloxy)aluminohydride. A new remarkably chemoselective reagent for the reduction of aldehydes in the presence of ketonesS. KrishnamurthyCite this: J. Org. Chem. 1981, 46, 22, 4628–4629Publication Date (Print):October 1, 1981Publication History Published online1 May 2002Published inissue 1 October 1981https://pubs.acs.org/doi/10.1021/jo00335a082https://doi.org/10.1021/jo00335a082research-articleACS PublicationsRequest reuse permissionsArticle Views401Altmetric-Citations54LEARN 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