gebhart/patrepeval huggingface dataset:
Effects of hypothyroidism on glucose and glutamine metabolism by the gut of the rat (1991)

1. The metabolism of glucose and glutamine was studied in the small intestine and the colon of rats after 4-5 weeks of hypothyroidism. 2. Hypothyroidism resulted in increases in the plasma concentrations of ketone bodies (P less than 0.05), cholesterol (P less than 0.001) and urea (P less than 0.001), but decreases in the plasma concentrations of free fatty acids (P less than 0.05) and triacylglycerol (P less than 0.001). These changes were associated with decreases in the plasma concentrations of total tri-iodothyronine, free tri-iodothyronine, total thyroxine and free thyroxine. 3. Hypothyroidism decreased both the DNA content (by 30.5%) and the protein content (by 23.6%) of intestinal mucosa, with the protein/DNA ratio remaining unchanged. The villi in the jejunum were shorter (P less than 0.05) and the crypt depth was decreased by about 26.5% in hypothyroid rats. 4. Portal-drained visceral blood flow showed no marked change in response to hypothyroidism, but was accompanied by decreased rates of extraction of glucose, lactate and glutamine and release of glutamate, alanine and ammonia. 5. Enterocytes and colonocytes isolated from hypothyroid rats showed decreased rates of utilization and metabolism of glucose and glutamine. 6. The maximal activities of hexokinase (EC 2.7.1.1), 6-phosphofructokinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40), citrate synthase (EC 4.1.3.28), oxoglutarate dehydrogenase (EC 1.2.4.2) and phosphate-dependent glutaminase (EC 3.5.1.2) were decreased in intestinal mucosal scrapings from hypothyroid rats. Similar decreases were obtained in colonic mucosal scrapings (except for citrate synthase and oxoglutarate dehydrogenase) from hypothyroid rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Volatile compounds in blood headspace and nasal breath (2017)

Breath analysis is a form of metabolomics that utilises the identification and quantification of volatile chemicals to provide information about physiological or pathological processes occurring within the body. An inherent assumption of such analyses is that the concentration of the exhaled gases correlates with the concentration of the same gas in the tissue of interest. In this study we have investigated this assumption by quantifying some volatile compounds in peripheral venous blood headspace, and in nasal breath collected in Tedlar bags obtained at the same time from 30 healthy volunteers, prior to analysis by selected ion flow tube mass spectrometry. Some endogenous compounds were significantly correlated between blood headspace and nasal breath, such as isoprene (r <sub>p</sub> = 0.63) and acetone (r <sub>p</sub> = 0.68), however many, such as propanol (r <sub>p</sub> = -0.26) and methanol (r <sub>p</sub> = 0.23), were not. Furthermore, the relative concentrations of volatiles in blood and breath varied markedly between compounds, with some, such as isoprene and acetone, having similar concentrations in each, while others, such as acetic acid, ammonia and methanol, being significantly more abundant in breath, and others, such as methanal, being detectable only in breath. We also observed that breath propanol and acetic acid concentrations were higher in male compared to female participants, and that the blood headspace methanol concentration was negatively correlated to body mass index. No relationship between volatile concentrations and age was observed. Our data suggest that breath concentrations of volatiles do not necessarily give information about the same compound in the blood stream. This is likely due to the upper airway contributing compounds over and above that originating in the circulation. An investigation of the relationship between breath volatile concentrations and that in the tissue(s) of interest should therefore become a routine part of the development process of breath-based biomarkers.
Efficient Photochemical Dihydrogen Generation Initiated by a Bimetallic Self-Quenching Mechanism (2016)

Artificial photosynthesis relies on coupling light absorption with chemical fuel generation. A mechanistic study of visible light-driven H<sub>2</sub> production from [Cp*Ir(bpy)H]<sup>+</sup> (1) has revealed a new, highly efficient pathway for integrating light absorption with bond formation. The net reaction of 1 with a proton source produces H<sub>2</sub>, but the rate of excited state quenching is surprisingly acid-independent and displays no observable deuterium kinetic isotopic effect. Time-resolved photoluminescence and labeling studies are consistent with diffusion-limited bimetallic self-quenching by electron transfer. Accordingly, the quantum yield of H<sub>2</sub> release nearly reaches unity as the concentration of 1 increases. This unique pathway for photochemical H<sub>2</sub> generation provides insight into transformations catalyzed by 1.
1,2-Benzisoxazol-3-yl diphenyl phosphate: a new, reactive activating agent for the synthesis of amides, esters, and peptides via condensation (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1,2-Benzisoxazol-3-yl diphenyl phosphate: a new, reactive activating agent for the synthesis of amides, esters, and peptides via condensationMitsuru Ueda and Hideaki OikawaCite this: J. Org. Chem. 1985, 50, 6, 760–763Publication Date (Print):March 1, 1985Publication History Published online1 May 2002Published inissue 1 March 1985https://pubs.acs.org/doi/10.1021/jo00206a006https://doi.org/10.1021/jo00206a006research-articleACS PublicationsRequest reuse permissionsArticle Views904Altmetric-Citations35LEARN 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
Replicative Potential and Telomere Length in Human Skeletal Muscle: Implications for Satellite Cell-Mediated Gene Therapy (1997)

In this study, we have evaluated the ability of human satellite cells isolated from subjects aged from 5 days to 86 years to proliferate in culture. Cells were cultivated until they became senescent. The number of cell divisions was calculated by counting the number of cells plated in culture compared to the number of cells removed following proliferation. Telomere length, which is known to decrease during each round of cell division, has been used to analyze the in vitro replicative capacity and in vivo replicative history of human satellite cells at isolation. The rate of telomere shortening in myonuclei of these muscle biopsies was also examined. Our results show that both proliferative capacity and telomere length of satellite cells decreases with age during the first two decades but that the myonuclei of human skeletal muscle are remarkably stable because telomere length in these myonuclei remains constant from birth to 86 years. The lack of shortening of mean terminal restriction fragments (TRF) in vivo confirms that skeletal muscle is a stable tissue with little nuclear turnover and therefore an ideal target for cell-mediated gene therapy. Moreover, our results show that it is important to consider donor age as a limiting factor to obtain an optimal number of cells. One of the gene transfer methods currently being explored is cell-mediated gene therapy. This technique involves the genetic manipulation of cells followed by their in vitro amplification. Skeletal muscle due to its stability and the presence of mononucleate myogenic precursor cells (satellite cells) has been suggested to be an ideal target for gene therapy. Satellite cells can be isolated from donor or host tissue, amplified in vitro, and then reinjected into host muscle where they will become incorporated into growing or regenerating muscle fibers. The success of cell-mediated gene therapy is related to the capacity of cells to proliferate during the stage of in vitro amplification and their ability to fuse with host muscle fibers subsequent to their transplantation. In this study, we have used telomere length to measure the in vitro replicative capacity of satellite cells. We have shown that both replicative capacity and telomere length decline rapidly during the first two decades of life but the myonuclei are stable because telomere length remains constant in adult muscle.
PU.1 and pRB Interact and Cooperate To Repress GATA-1 and Block Erythroid Differentiation (2003)

PU.1 and GATA-1 are two hematopoietic specific transcription factors that play key roles in development of the myeloid and erythroid lineages, respectively. The two proteins bind to one another and inhibit each other's function in transcriptional activation and promotion of their respective differentiation programs. This mutual antagonism may be an important aspect of lineage commitment decisions. PU.1 can also act as an oncoprotein since deregulated expression of PU.1 in erythroid precursors causes erythroleukemias in mice. Studies of cultured mouse erythroleukemia cell lines indicate that one aspect of PU.1 function in erythroleukemogenesis is its ability to block erythroid differentiation by repressing GATA-1 (N. Rekhtman, F. Radparvar, T. Evans, and A. I. Skoultchi, Genes Dev. 13:1398-1411, 1999). We have investigated the mechanism of PU.1-mediated repression of GATA-1. We report here that PU.1 binds to GATA-1 on DNA. We localized the repression activity of PU.1 to a small acidic N-terminal domain that interacts with the C pocket of pRB, a well-known transcriptional corepressor. Repression of GATA-1 by PU.1 requires pRB, and pRB colocalizes with PU.1 and GATA-1 at repressed GATA-1 target genes. PU.1 and pRB also cooperate to block erythroid differentiation. Our results suggest that one of the mechanisms by which PU.1 antagonizes GATA-1 is by binding to it at GATA-1 target genes and tethering to these sites a corepressor that blocks transcriptional activity and thereby erythroid differentiation.
Renal effects of soluble guanylate cyclase stimulators and activators: A review of the preclinical evidence (2015)

Direct stimulation of soluble guanylate cyclase (sGC) is emerging as a potential new approach for the treatment of renal disorders. sGC catalyzes the formation of cyclic guanosine monophosphate (cGMP), deficiency of which is implicated in the pathogenesis of chronic kidney disease (CKD). Therefore, new classes of drugs sGC stimulators and activators are being investigated in preclinical models under conditions where nitric oxide is deficient. In preclinical models with different etiologies of CKD, the sGC stimulators BAY 41-2272, BAY 41-8543, BAY 60-4552, riociguat and vericiguat and the sGC activators cinaciguat, ataciguat, BI 703704 and GSK2181236A have shown consistently renoprotective effects. Clinical trials are required to confirm these findings in humans, and to ascertain whether these agents could provide a future alternative to guideline-recommended treatments.
Wireless therapeutic endoscopic capsule: in vivo experiment (2008)

This study reports the first successful in vivo surgical experiment using a wireless endoscopic capsule, paving the way to a new generation of capsule devices able to perform both diagnostic and therapeutic tasks.
Cardiovascular Regeneration and Stem Cell Therapy (2007)

Contributors. Preface. Introduction. Annarosa Leri, Piero Anversa, William Frishman. Part I Stem Cell Biology. 1 Homing of Stem Cells and Tissue Injury. Ayelet Dar, Orit Kollet, Tsvee Lapidot. 2 Adult Stem Cell Plasticity: Lineage potential on a Continuum. Peter J. Quesenberry, Gerald Colvin, Mehrdad Abedi. 3 Embryonic Stem Cells and Cardiogenesis. Timothy J. Kamp, Gary E. Lyons. 4 Mesenchymal Stem Cell-Derived Cardiomyogenic Cells. Keiichi Fukuda, Jun Fujita, Daihiko Hakuno, Shinji Makino. 5 Bone Marrow Cells and Vascular Growth. Takayuki Asahara. 6 Progenitor Cells and Vascular Repair. Kaushik Mandal, Marjan Jahangiri, Qingbo Xu. Part II Cardiac Progenitor Cells in the Adult Heart. 7 Cardiac Side Population Cells: Phenotype and Functional Significance. Ronglih Liao, Frederic Mouquet, Otmar Pfister. 8 Phenotype and Function of c-kit Positive-Derived Amplifying Myocytes. Rachel Wilson, Xiongwen Chen, Hajime Kubo, Remus Berretta, Steven Houser. 9 Cardiac Stem Cells and their Niches. Annarosa Leri, Alessandro Boni, Robert Siggins, Angelo Nascimbene, Toru Hosoda. 10 Activation of the Local Regenerative System of the Heart. Antonia Germani, Federica Limana, Maurizio C. Capogrossi. Part III Progenitor Cells and the Diseased Heart. 11 Embryonic Stem Cells and Myocardial Regeneration. Ahmad Y. Sheikh, Phillip C. Yang, Joseph C. Wu, Robert C. Robbins. 12 Bone Marrow-Derived Cells in Myocardial Repair and Regeneration. Raj Kishore, Douglas W. Losordo. 13 Endothelial Progenitor Cells And The Infarcted Heart. Stefanie Dimmeler, Masamichi Koyanagi, Carmen Urbich, Andreas M. Zeiher. 14 Cytokines and Heart Remodeling. Issei Komuro, Hiroyuki Takano. 15 IGF-1, Muscle Progenitors and Heart Failure. Nadia Rosenthal, Nadine Winn, Maria Paola Santini. Part IV Cardiac Progenitor Cells and Heart Failure. 16 Cardiac Stem Cells and the Diabetic Cardiomyopathy. Jan Kajstura, Nicole LeCapitaine, Maria Loredo, Marco Giorgio, Thomas S. Mitchell, Susanna Valentini, Francesco Rotatori, Pier Giuseppe Pelicci. 17 Stem Cells and Cardiac Aging. Roberto Bolli, Piero Anversa. 18 Bioengineered Scaffolds: Myocytes, Endothelial Cells and Cardiac Repair. Vincent F.M. Segers, Richard T. Lee. 19 Gene Therapy and Cellular Therapy in Cardiac Repair. Mark A. Sussman. 20 Cardiac Stem Cells and the Failing Heart. Piero Anversa, Konrad Urbanek, Claudia Bearzi, Antonella De Angelis, Marcello Rota. 21 Myocardial Infarction: Risks and Hope. Marc A. Pfeffer. Part V Future Directions. 22 Conclusions - Future Directions. Piero Anversa, Edmund H. Sonnenblick, William Frishman. Index
Molecular Differences Caused by Differentiation of 3T3-L1 Preadipocytes in the Presence of either Dehydroepiandrosterone (DHEA) or 7-Oxo-DHEA (2002)

The effects of dehydroepiandrosterone (DHEA) and 7-oxo-DHEA on the cell size, adiposity, and fatty acid composition of differentiating 3T3-L1 preadipocyte cells are correlated with stearoyl-CoA desaturase (SCD) expression (mRNA and protein levels) and enzyme activity. Fluorescence-activated cell sorting shows that preadipocyte cells treated with methylisobutylxanthine, dexamethasone, and insulin (MDI) plus DHEA comprise a population distribution of predominantly large cells with reduced adiposity. In contrast, cells treated with MDI plus 7-oxo-DHEA comprise a population distribution of almost equal proportions of small and large cells that have an adiposity equivalent to cells differentiated with MDI alone. The cells treated with MDI plus DHEA have significantly reduced levels of total fatty acid, mainly due to a dramatic reduction in the level of palmitoleic (Delta(9)-16:1) acid. The cells treated with MDI plus 7-oxo-DHEA have a significantly increased level of total fat, primarily due to increased levels of Delta(9)-16:1 and palmitic (16:0) acids. At the molecular level, the DHEA-treated cells contain lowered amounts of SCD1 mRNA and antibody-detectable desaturase protein, while 7-oxo-DHEA-treated cells contained elevated levels of SCD1 mRNA and protein. Inhibition of differentiation in DHEA-treated cells was also suggested by a reduction in the mRNA level of the adipogenic gene aP2. At the level of microsomal enzymatic activity, SCD activity was decreased in DHEA-treated cells while the SCD activity was increased in 7-oxo-DHEA-treated cells. The changes in mRNA levels and enzyme activity were concentration-dependent and appeared as early as day 3 of the differentiation protocol. The results show that DHEA and 7-oxo-DHEA have distinct modes of action with respect to the complex transcriptional cascade required for differentiation. Furthermore, differences in the insulin-stimulated uptake of 2-deoxyglucose and in the activity of carnitine palmitoyl transferase observed from either DHEA- or 7-oxo-DHEA-treated cells support the ability of DHEA to produce a thermogenic effect in differentiating preadipocytes, while 7-oxo-DHEA promotes differentiation without other changes typical of thermogenesis.
Regulation of bioactive IL-12 production in lipopolysaccharide-stimulated human monocytes is determined by the expression of the p35 subunit (1996)

IL-12 enhances IFN-gamma production by NK cells and T lymphocytes and plays a pivotal role in the development of Th1 cells. Bioactive IL-12 (p70) is composed of two subunits, p35, which is only secreted as part of the p70 dimer, and p40, which can also be secreted by itself. The IL-12 subunits are encoded by two separate genes. Therefore, we studied to what extent the expression of each of the subunits contributes to the regulation of IL-12 production. We found that in LPS-stimulated whole blood and purified monocytes, p70 and p40 production are enhanced by IFN-gamma and inhibited by IL-10 and IL-4. However, IFN-gamma and IL-10 had stronger effects on p70 production than on p40 production, and IL-4 affected p40 production more strongly. Concomitantly, in all experimental conditions tested, p40 production greatly exceeded p70 production, suggesting that p35 expression was limiting. Analysis of p35 and p40 mRNA expression by PCR confirmed this notion. Resting purified monocytes expressed neither p40 nor p35 mRNA. The effects of IFN-gamma, IL-10, and IL-4 on the p35 mRNA expression in LPS-stimulated purified monocytes were similar to the effects of these cytokines on p70 protein production, and the p40 mRNA expression corresponded to p40 protein production. Our results imply that production of the two IL-12 subunits is differently regulated for each subunit, mainly at the level of mRNA expression, and that the level of bioactive IL-12 production in monocytes in response to LPS and cytokines is determined by the level of p35 expression.
Towards Internet-scale multi-view stereo (2010)

This paper introduces an approach for enabling existing multi-view stereo methods to operate on extremely large unstructured photo collections. The main idea is to decompose the collection into a set of overlapping sets of photos that can be processed in parallel, and to merge the resulting reconstructions. This overlapping clustering problem is formulated as a constrained optimization and solved iteratively. The merging algorithm, designed to be parallel and out-of-core, incorporates robust filtering steps to eliminate low-quality reconstructions and enforce global visibility constraints. The approach has been tested on several large datasets downloaded from Flickr.com, including one with over ten thousand images, yielding a 3D reconstruction with nearly thirty million points.
Enzyme Molecular Mechanism as a Starting Point to Design New Inhibitors: A Theoretical Study of O-GlcNAcase (2011)

O-Glycoprotein 2-acetamino-2-deoxy-β-D-glucopyranosidase (O-GlcNAcase) hydrolyzes O-linked 2-acetamido-2-deoxy-β-D-glucopyranoside (O-GlcNAc) residues from post-translationally modified serine/threonine residues of nucleocytoplasmic protein. The chemical process involves substrate-assisted catalysis, where two aspartate residues have been identified as the two key catalytic residues of O-GlcNAcase. In this report, the first step of the catalytic mechanism used by O-GlcNAcase involving substrate-assisted catalysis has been studied using a hybrid quantum mechanical/molecular mechanical (QM/MM) Molecular Dynamics (MD) calculations. The free energy profile shows that the formation of the oxazoline intermediate in the O-GlcNAcase catalytic reaction takes place by means of a stepwise mechanism. The first step would be a cyclization of the acetomide group, which seems to be dependent on the proton transfer from a conserved aspartate, Asp298 in Clostridium perfringens O-GlcNAcase. From this new intermediate, a proton is transferred from the azoline ring to another conserved aspartate (Asp297) thus forming the oxazoline ion and departure of the aglycone. In addition, averaged values of protein-substrate interaction energy along the reaction path shows that, in fact, the transition states present the highest binding affinities. A deeper analysis of the binding contribution of the individual residues shows that Asp297, Asp298, and Asp401 are basically responsible of the stabilization of these complexes. These results would explain why O-(2-acetamido-2deoxy-d-glucopyranosylidene)amino-N-phenycarbamate (PUGNAc), 1,2-dideoxy-2'-methyl-α-D-glucopyranoso-[2,1-d]-Δ2'-thiazoline (NAG-thiazoline), and GlcNAcstatin derivatives are potent inhibitors of this enzyme, resembling the two transition states of the O-GlcNAcase catalytic reaction path. These results may be useful to rational design compounds with more interesting inhibitory activity.
Sequential cardiorespiratory patterns in septic shock (1983)

Sequential hemodynamic and oxygen transport monitoring was performed in 33 patients with septic shock to define the temporal pattern of physiologic events. Measurements taken over a 24-h period before the hypotensive crisis, defined as the lowest initial mean arterial pressure (MAP), were compared to those taken during the 48 h thereafter. In the 24-h period before the hypotensive crisis, there were increases in cardiac index (CI), central venous pressure (CVP), pulmonary capillary wedge pressure (WP), pulmonary vascular resistance index (PVRI), and pulmonary shunt (Qsp/Qt), but decreases in MAP, systemic vascular resistance index (SVRI) and oxygen delivery (Do2). When sequential cardiorespiratory patterns were examined, oxygen consumption (VO2) fell transiently to significantly low values 12 h before as well as at the time of the hypotensive crisis. SVRI fell and CI rose to values significantly different from normal in the 4 h before the low MAP. During the subsequent 48 h after the hypotensive crisis, CI, CVP, WP, PVRI and Qsp/Qt remained elevated. Values for MAP, SVRI, DO2, and VO2 were significantly reduced. These results demonstrate the existence of antecedent cardiorespiratory alterations that precede the hypotensive episode in septic shock and suggest that flow maldistribution in the systemic circulation is an early event with possible pathogenic significance.
Gene therapy using bone marrow transplantation. (1987)

As a result of new techniques in molecular biology, the basic defects in a variety of genetic diseases have been characterized and the corresponding normal genes cloned. Methods have been devised for transferring specific genes with high efficiency into various cell types that exploit the use of replication-defective retroviruses as vectors. Bone marrow may be the ideal target for these attempts to transfer genes, because it contains self-renewing stem cells and because it can readily be collected by standard techniques, manipulated ex vivo as required with comparative ease and then reinfused. In a murine system, recent studies have shown that genes can indeed be incorporated into haemopoietic stem cells that can then completely reconstitute the marrows of syngeneic recipients. Thus far, such genes after transfer have not been appropriately expressed in vivo, although appreciable expression has been documented in cell culture studies in vitro. It is reasonable to expect that improvements in the design of retroviral vectors should permit appropriate expression of a transferred gene. When this is achieved, the use of bone marrow transplantation for gene transfer will offer new options for therapy.