gebhart/patrepeval huggingface dataset:
Purification and Properties of the Acetohydroxy Acid Isomeroreductase of Salmonella typhimurium (1969)

α-Acetohydroxy acid isomeroreductase, which catalyzes both the second step specific to valine biosynthesis and the third step specific to isoleucine biosynthesis, has been purified from derepressed Salmonella typhimurium. The enzyme appears to be homogeneous in the ultracentrifuge and by immunodiffusion in agar. The molecular weight, as determined by sedimentation equilibrium ultracentrifugation, is approximately 220,000. The enzyme is stereospecific for the B side of NADPH. At pH 7.5, the optimal pH for the isomeroreductase, the reversibility of the reaction cannot be shown, but at higher values the reaction is readily reversible. The pH optimum of the reverse reaction is about 9.4. The purified enzyme catalyzes the isomerization of α-keto-β-hydroxyisovalerate to α-acetolactate and the NADPH-linked reduction of α-keto-β-hydroxyisovalerate to α,β-dihydroxyisovalerate as well as the over-all conversion of α-acetolactate to α,β-dihydroxyisovalerate. The ratio of these activities remains constant during purification and the coenzyme and Mg++ requirements suggest that the isomerase and reductase activities are inherent properties of the enzyme. However, experiments with labeled substrate indicate that α-keto-β-hydroxyisovalerate is not a free intermediate of the over-all reaction.
Intimidad y propia imagen: los ecos del common law americano y la evolución de la jurisprudencia constitucional española (2014)

If we examine the Spanish constitutional jurisprudence about the disputed relationships between freedom of speech and personality rights, such as privacy and one s own image (right to publicity), it 1 Es abogada en ejercicio y profesora del Departamento de Derecho Publico del Estado de la Universidad Carlos III de Madrid, donde imparte Information Law in Multimedia Context dentro del Grado bilingue de Periodismo y Derecho Audiovisual en el Master de Derecho de las Telecomunicaciones y Tecnologias de la Informacion. Tambien es profesora de Propiedad Intelectual en la Universidad Complutense (Centro de Estudios Superiores Felipe II).
Glutathione S-transferase omega-1 modifiesage-at-onset of Alzheimer disease and Parkinson disease (2003)

We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of 'genomic convergence' to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1beta. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.
Testosterone Formation and Metabolism During Male Sexual Differentiation in the Human Embryo (1974)

The formation by the gonads of [3H] testosterone from [7α-3H]pregnenolone and [1,2-3H] progesterone and the metabolism of [1,2-3H]testosterone by various tissues have been studied in 33 human fetuses that varied in age from phenotypically undifferentiated stages (1–3 cm crown-rump length) to sexually differentiated male and female embryos greater than 21 cm in length. In the first series of studies utilizing thinlayer and celite column chromatography for quantification of the metabolic products following incubation of the gonads with the C21 steroids, it was concluded that testosterone is the principal androgen formed by the fetal testis at the time of male sexual differentiation. The capacity for testosterone formation from these precursors was shown to rise from undetectable levels at 1–3 cm of development to maximal rates of about 150 pinoles/10 mg tissue/2 hr in the testes obtained from embryos of 7.1–9 cm crown-rump length, a sequence that correlates closely with the androgenmediated events in male sexual differentiation. No testosterone formation was demonstrated in the ovaries at any stage of development. To characterize the mechanisms involved in androgen-mediated development of the male urogenital tract, the rate of conversion of [1,2-3H] testosterone to [3H]dihydrotestosterone was measured in a variety of tissues in these embryos. Dihydrotestosterone formation was most rapid in the tissues of the urogenital tract. In the urogenital sinus and urogenital tubercle the capacity for dihydrotestosterone formation was maximal prior to the onset of male differentiation, suggesting that dihydrotestosterone is probably the effective intracellular androgen that mediates male development in these tissues. In contrast, in the wolffian ducts the ability to form dihydrotestosterone could not be demonstrated until late in male differentiation, indicating that testosterone itself is the likely hormone that initiates the development of this anlage into the epididymis, vas deferens, and seminal vesicle. The implications of these findings for the elucidation of the pathogenesis of several disorders of male sexual differentiation have been discussed
Production of functional transgenic mice by DNA pronuclear microinjection. (2004)

Successful experiments involving the production of transgenic mice by pronuclear microinjection are currently limited by low efficiency of random transgene integration into the mouse genome. Furthermore, not all transgenic mice express integrated transgenes, or in other words are effective as functional transgenic mice expressing the desired product of the transgene, thus allowing accomplishment of the ultimate experimental goal--in vivo analysis of the function of the gene or gene network. The purpose of this review is to look at the current state of transgenic technology, utilizing a pronuclear microinjection method as the most accepted way of gene transfer into the mouse genome.
Formation-Damaging Characteristics of Mixed Metal Hydroxide Drill-In Fluids and a Comparison With Polymer-Base Fluids (1999)

Summary Horizontal wells are commonly completed without casing and the fluids used to drill said sections can have a significant effect on the production outcome. Mixed metal hydroxide (MMH)/bentonite-based fluids are compared to two commonly used reservoir drill-in fluids (DIFs) with respect to filter-cake characteristics and regain in permeability. The MMH fluids are found to produce filter cakes with unique features which result in efficient backflow without need for chemical treatment. Return permeability results which equal or exceed those for more commonly used DIFs raise questions over the conventional view that bentonite-containing DIFs are harmful to reservoirs.
How Does the Eye Breathe? (2003)

Visual performance of the vertebrate eye requires large amounts of oxygen, and thus the retina is one of the highest oxygen-consuming tissues of the body. Here we show that neuroglobin, a neuron-specific respiratory protein distantly related to hemoglobin and myoglobin, is present at high amounts in the mouse retina (approximately 100 microm). The estimated concentration of neuroglobin in the retina is thus about 100-fold higher than in the brain and is in the same range as that of myoglobin in the muscle. Neuroglobin is expressed in all neurons of the retina but not in the retinal pigment epithelium. Neuroglobin mRNA was detected in the perikarya of the nuclear and ganglion layers of the neuronal retina, whereas the protein was present mainly in the plexiform layers and in the ellipsoid region of photoreceptor inner segment. The distribution of neuroglobin correlates with the subcellular localization of mitochondria and with the relative oxygen demands, as the plexiform layers and the inner segment consume most of the retinal oxygen. These findings suggest that neuroglobin supplies oxygen to the retina, similar to myoglobin in the myocardium and the skeletal muscle.
Reduction of Myocardial Infarct Size After Ischemia and Reperfusion by the Glycosaminoglycan Pentosan Polysulfate (1999)

Activation of the complement system contributes to the tissue destruction associated with myocardial ischemia/reperfusion. Pentosan polysulfate (PPS), a negatively charged sulfated glycosaminoglycan (GAG) and an effective inhibitor of complement activation, was studied for its potential to decrease infarct size in an experimental model of myocardial ischemia/reperfusion injury. Open-chest rabbits were subjected to 30-min occlusion of the left coronary artery followed by 5 h of reperfusion. Vehicle (saline) or PPS (30 mg/kg/h) was administered intravenously immediately before the onset of reperfusion and every hour during the reperfusion period. Treatment with PPS significantly (p < 0.05) reduced infarct size as compared with vehicle-treated animals (27.5+/-2.9% vs. 13.34+/-2.6%). Analysis of tissue demonstrated decreased deposition of membrane-attack complex and neutrophil accumulation in the area at risk. The results indicate that, like heparin and related GAGs, PPS possesses the ability to decrease infarct size after an acute period of myocardial ischemia and reperfusion. The observations are consistent with the suggestion that PPS may mediate its cytoprotective effect through modulation of the complement cascade.
The Genes of Capsicum (2006)

Pepper ( Capsicum spp.) is one of the most cultivated vegetable and spice crops in the world. Capsicum genetics have been extensively studied, but the most recent Capsicum gene list was published more than a decade ago. Since then, new genes have been described. This updated gene list provides detailed descriptions of genes, including the genes' characteristics, the genetic background of the mutants/lines, action mechanisms of genes, gene interactions, molecular markers, and chromosome localization when available. This new list includes 292 genes for morphological traits; physiological traits; sterility; and resistance to diseases, nematodes, and herbicides, which includes the 92 genes that have not been previously described.
SEQUENCE ANALYSIS OF SOMATOMEDIN-C: CONFIRMATION OF IDENTITY WITH INSULIN-LIKE GROWTH FACTOR I (1983)

Somatomedin-C (Sm-C) was purified from Cohn fraction IV of human plasma by previously published methods. Purity was established by SDS polyacrylamide electrophoresis followed by silver staining of the gel. Amino acid analysis of an acid hydrolysate revealed no significant discrepancies from the amino acid composition of insulin-like growth factor I (IGF-I). The first 24 residues beginning at the amino terminal glycine were identical to the corresponding residues in IGF-I. Tryptic and chymotryptic degradation followed by determination of the amino acid composition and sequence of the resultant peptides was used to complete the primary structure of Sm-C. The results of these studies document that Sm-C and IGF-I are identical peptides, thus supporting previous observations that Sm-C and IGF-I are qualitatively and quantitatively indistinguishable in radioligand and biological assay systems.
Targeted inactivation of sister of P-glycoprotein gene ( spgp ) in mice results in nonprogressive but persistent intrahepatic cholestasis (2001)

Mutations in the sister of P-glycoprotein (Spgp) or bile salt export pump (BSEP) are associated with Progressive Familial Intrahepatic Cholestasis (PFIC2). Spgp is predominantly expressed in the canalicular membranes of liver. Consistent with in vitro evidence demonstrating the involvement of Spgp in bile salt transport, PFIC2 patients secrete less than 1% of biliary bile salts compared with normal infants. The disease rapidly progresses to hepatic failure requiring liver transplantation before adolescence. In this study, we show that the knockout of spgp gene in mice results in intrahepatic cholestasis, but with significantly less severity than PFIC2 in humans. Some unexpected characteristics are observed. Notably, although the secretion of cholic acid in mutant mice is greatly reduced (6% of wild-type), total bile salt output in mutant mice is about 30% of wild-type. Also, secretion of an unexpectedly large amount of tetra-hydroxylated bile acids (not detected in wild-type) is observed. These results suggest that hydroxylation and an alternative canalicular transport mechanism for bile acids compensate for the absence of Spgp function and protect the mutant mice from severe cholestatic damage. In addition, the spgp(-/-) mice display a significant increase in the secretion of cholesterol and phospholipids into the bile. This latter observation in spgp(-/-) mice suggests that intrahepatic, rather than intracanalicular, bile salts are the major driving force for the biliary lipid secretion. The spgp(-/-) mice thus provide a unique model for gaining new insights into therapeutic intervention for intrahepatic cholestasis and understanding mechanisms associated with lipid homeostasis.
Efficient Homogeneous Catalytic Hydrogenation of Esters to Alcohols (2006)

With open arms: A ruthenium PNN complex (see scheme) catalyzes the hydrogenation of esters in high yields under neutral conditions. The analogous PNP complex is less active. A mechanism is proposed based on the hemilabile nature of the PNN ligand which allows a vacant site to be created by decoordination of the CH2NEt2 arm.
New insights into p53 based therapy. (2011)

A common step in human cancer is the inactivation of the p53 tumor suppressor pathway. This occurs either by mutations in the coding region of the p53 gene itself, or equally commonly, by inactivation of pathways that are required for p53 to exert its cellular function. Dramatic new results from animal models and the widespread availability of p53 activating small molecules are yielding important new insights into the therapeutic and toxic effects of p53 and how these can be exploited for improving therapy of cancer and other diseases.
Interleukin 12 and B7-1 costimulatory molecule expressed by an adenovirus vector act synergistically to facilitate tumor regression (1997)

Stimulation of antitumor immune mechanisms is the primary goal of cancer immunotherapy, and accumulating evidence suggests that effective alteration of the host-tumor relationship involves immunomodulating cytokines and also the presence of costimulatory molecules. To examine the antitumor effect of direct in vivo gene transfer of murine interleukin 12 (IL-12) and B7-1 into tumors, we developed an adenovirus (Ad) vector, AdIL12-B7-1, that encodes the two IL-12 subunits in early region 1 (E1) and the B7-1 gene in E3 under control of the murine cytomegalovirus promoter. This vector expressed high levels of IL-12 and B7-1 in infected murine and human cell lines and in primary murine tumor cells. In mice bearing tumors derived from a transgenic mouse mammary adenocarcinoma, a single intratumoral injection with a low dose (2.5 x 10(7) pfu/mouse) of AdIL12-B7-1 mediated complete regression in 70% of treated animals. By contrast, administration of a similar dose of recombinant virus encoding IL-12 or B7-1 alone resulted in only a delay in tumor growth. Interestingly, coinjection of two different viruses expressing either IL-12 or B7-1 induced complete tumor regression in only 30% of animals treated at this dose. Significantly, cured animals remained tumor free after rechallenge with fresh tumor cells, suggesting that protective immunity had been induced by treatment with AdIL12-B7-1. These results support the use of Ad vectors as a highly efficient delivery system for synergistically acting molecules and show that the combination of IL-12 and B7-1 within a single Ad vector might be a promising approach for in vivo cancer therapy.
Preferential gene expression in quiescent human lung fibroblasts. (1993)

The exit from the proliferative cell cycle into a reversible quiescence (G0) is an active process that is not yet well understood at the molecular level. Investigation of G0-specific gene expression is an important step in studying the mechanism regulating the entrance to quiescence. Using the human embryo lung fibroblast (WI38) as a model system, we have isolated complementary DNA clones that are expressed at a higher level in quiescent cells than in logarithmically growing cells. We have identified complementary DNAs from eight genes including collagen alpha 1(VI), collagen alpha 1(III), decorin, complement C1r, collagen alpha 1(I), collagen alpha 2(I), and two novel genes, Q6 and Q10. We have named this class of quiescence-inducible genes quiescins. Expression of these genes was induced just as proliferation slowed, as indicated by the level of histone H2B mRNA, [3H]-thymidine incorporation, and cell number. The level of expression of the novel genes, Q6 and Q10, increased at the same time as the other genes. Q6 has two mRNAs of 3 and 4 kb, whereas Q10 mRNA is about 1.0 kb. The expression of the quiescins was not induced by blocking the cell cycle in S phase with aphidicolin or in G1 with lovastatin. However, the genes were highly induced by trypsinization or scraping of the cells during logarithmic growth. This induction was not blocked by inhibitors of RNA synthesis. The expression of decorin and Q6 was very low in SV40-transformed cells (VA13) either in logarithmic growth or at high density, whereas the gene Q10 was expressed more highly in VA13 than in WI38 cells. The finding that expression of some components of the extracellular matrix is induced as cells enter G0 suggests that they may have a role in both the induction and the maintenance of the quiescent state. The quiescins will serve as molecular markers for the investigation of mechanisms that regulate the onset of quiescence.
Phytochrome assembly in living cells of the yeast Saccharomyces cerevisiae. (1994)

The biological activity of the plant photoreceptor phytochrome requires the specific association of a linear tetrapyrrole prosthetic group with a large apoprotein. As an initial step to develop an in vivo assay system for structure-function analysis of the phytochrome photoreceptor, we undertook experiments to reconstitute holophytochrome in the yeast Saccharomyces cerevisiae. Here we show that yeast cells expressing recombinant oat apophytochrome A can take up exogenous linear tetrapyrroles, and, in a time-dependent manner, these pigments combine with the apoprotein to form photoactive holophytochrome in situ. Cell viability measurements indicate that holophytochrome assembly occurs in living cells. Unlike phytochrome A in higher plant tissue, which is rapidly degraded upon photoactivation, the reconstituted photoreceptor appears to be light stable in yeast. Reconstitution of photoactive phytochrome in yeast cells should enable us to exploit the power of yeast genetics for structure-function dissection of this important plant photoreceptor.
The Coronavirus Transmissible Gastroenteritis Virus Causes Infection after Receptor-Mediated Endocytosis and Acid-Dependent Fusion with an Intracellular Compartment (1998)

Aminopeptidase N is a species-specific receptor for transmissible gastroenteritis virus (TGEV), which infects piglets, and for the 229E virus, which infects humans. It is not known whether these coronaviruses are endocytosed before fusion with a membrane of the target cell, causing a productive infection, or whether they fuse directly with the plasma membrane. We have studied the interaction between TGEV and a cell line (MDCK) stably expressing recombinant pig aminopeptidase N (pAPN). By electron microscopy and flow cytometry, TGEV was found to be associated with the plasma membrane after adsorption to the pAPN-MDCK cells. TGEV was also observed in endocytic pits and apical vesicles after 3 to 10 min of incubation at 38 degrees C. The number of pits and apical vesicles was increased by the TGEV incubation, indicating an increase in endocytosis. After 10 min of incubation, a distinct TGEV-pAPN-containing population of large intracellular vesicles, morphologically compatible with endosomes, was found. A higher density of pAPN receptors was observed in the pits beneath the virus particles than in the surrounding plasma membrane, indicating that TGEV recruits pAPN receptors before endocytosis. Ammonium chloride and bafilomycin A1 markedly inhibited the TGEV infection as judged from virus production and protein biosynthesis analyses but did so only when added early in the course of the infection, i.e., about 1 h after the start of endocytosis. Together our results point to an acid intracellular compartment as the site of fusion for TGEV.
The Effects of Glyceride Structure on Absorption and Metabolism (1991)

The subtle effects of the stereochemistry of acyl glycerols are apparent from the cited studies. It is not adequate to simply measure the fatty acid composition of dietary lipids or chylomicrons generated from them. To understand the importance of stereospecific acyl glycerols, simplification of the systems is necessary because of the incredible diversity found among dietary triacylglycerols. By feeding simple analogues corresponding to major triacylglycerols found in oils and fats it should be possible to determine the absorption, uptake into the mucosa, resynthesis into chylomicrons, and the stereospecificity that remains. Hydrolysis and uptake of these defined chylomicron triacylglycerols into adipose tissue or muscle could be followed and stereospecificity again determined in depot fats. Finally, the composition of the remnants, particularly the core and surface, and of the bound apoproteins needs to be related to their plasma residence time, hepatic removal, and deposition in nonhepatic tissues such as spleen, bone marrow, and arterial intima. Since increased serum cholesterol and atherogenicity in animals have been related to different dietary fats, some of the effects noted here, that is the retention of certain kinds of remnants in plasma, may lead to increased serum cholesterol and atherogenesis. We must study the metabolism of a few key stereospecific triacylglycerols in more detail to increase our understanding of their effects on hypercholesterolemia and atherogenesis.
L'échec de l'État dans les pays en développement et les stratégies de réforme institutionnelle (2003)

le cas échéant, des conditions générales de la licence souscrite par votre établissement.
Sensitivity Analysis for Simulations via Likelihood Ratios (1989)

We present a simple method of estimating the sensitivity of quantities obtained from simulation with respect to a class of parameters. Here sensitivity means the derivative of an expectation with respect to a parameter. The class of parameters includes, for example, Poisson rates, discrete probabilities, and the mean and variance of a Normal distribution. The method is extremely well suited to regenerative simulation, and can be implemented on extant simulations with little effort, increase in running time, or memory requirements. It is based on some change-of-measure formulas derived from likelihood ratios. In addition to the theorems that underly the technique, we present some numerical examples.