gebhart/patrepeval huggingface dataset:
Evidence showing that a proline-specific endopeptidase has an absolute requirement for a trans peptide bond immediately preceding the active bond (1983)

The proline-specific endopeptidase (EC 3.4.21.26) from Flavobacterium meningosepticum is specific for the cleavage of peptide bonds on the C-terminal side of prolyl residues. Such bonds will normally exist in the all-trans configuration. However, the preceding peptide bond in the sequence (i.e., on the N-terminal side of the prolyl residue) will exist as a mixture of cis and trans forms in solution. In this study, the activity of the proline-specific endopeptidase toward the substrates N-Cbz-Gly-Pro-MCA (where MCA = 4-methylcoumarinyl-7-amine) and N-Cbz-Gly-Pro-Leu-Gly has been examined. At a high ratio of enzyme activity/substrate concentration, the hydrolysis pattern for each substrate shows two well-separated kinetic phases. It is concluded that the fast kinetic phase, whose velocity depends on enzyme concentration, results from the direct hydrolysis of the active substrate bond (i.e., either the Pro-MCA or Pro-Leu bond, respectively) in molecules where the preceding Gly-Pro bond is trans. The slow phase, whose velocity is independent of enzyme concentration, is rate-limited by the cis-to-trans isomerization of those substrate molecules which initially have the preceding Gly-Pro bond in the cis configuration. That is, substrate molecules having the cis form of the Gly-Pro bond which precedes the active bond cannot be hydrolyzed directly but must first isomerize to the trans form before cleavage can occur. The amplitude, relaxation time, and activation energy for the slow phase are consistent with this interpretation. Thus, the proline-specific endopeptidase from Flavobacterium has an absolute requirement for a trans peptide bond at the position immediately preceding the active bond.
Prediction of tissular body composition from protein and lipid deposition in growing pigs1 (1995)

Tissular and chemical body composition were measured for 85 pigs that were serially slaughtered between 15 and 110 kg BW and considered lean (boars from a Synthetic Line and the Piétrain breed), conventional (boars, gilts, and barrows from the Large White breed), or obese (Meishan barrows). These six groups were expected to be quite different with regard to their body composition. Tissular body composition was predicted from chemical body composition, according to nonlinear regression models. Common relationships were obtained for lean and conventional pigs (Group effect: P > .05). Empty body weight and the weight of adipose tissues were predicted directly from the amounts of body protein and lipid, whereas for estimation of weights of carcass, muscle, and lean, the prediction was improved when the weight of offals (visceral organs and blood) was also included in the model. Validation of prediction models on literature data indicated good agreement between calculated and measured values (R2 > .90). These relationships were not applicable to Meishan barrows. In pig growth modeling approaches, proposed equations can be used in order to predict the tissular composition of body weight gain and commercial value at slaughter.
Engineered Pentafunctional Minicellulosome for Simultaneous Saccharification and Ethanol Fermentation in Saccharomyces cerevisiae (2014)

Several yeast strains have been engineered to express different cellulases to achieve simultaneous saccharification and fermentation of lignocellulosic materials. However, successes in these endeavors were modest, as demonstrated by the relatively low ethanol titers and the limited ability of the engineered yeast strains to grow using cellulosic materials as the sole carbon source. Recently, substantial enhancements to the breakdown of cellulosic substrates have been observed when lytic polysaccharide monooxygenases (LPMOs) were added to traditional cellulase cocktails. LPMOs are reported to cleave cellulose oxidatively in the presence of enzymatic electron donors such as cellobiose dehydrogenases. In this study, we coexpressed LPMOs and cellobiose dehydrogenases with cellobiohydrolases, endoglucanases, and β-glucosidases in Saccharomyces cerevisiae. These enzymes were secreted and docked onto surface-displayed miniscaffoldins through cohesin-dockerin interaction to generate pentafunctional minicellulosomes. The enzymes on the miniscaffoldins acted synergistically to boost the degradation of phosphoric acid swollen cellulose and increased the ethanol titers from our previously achieved levels of 1.8 to 2.7 g/liter. In addition, the newly developed recombinant yeast strain was also able to grow using phosphoric acid swollen cellulose as the sole carbon source. The results demonstrate the promise of the pentafunctional minicellulosomes for consolidated bioprocessing by yeast.
Osteoclast Precursor Interaction with Bone Matrix Induces Osteoclast Formation Directly by an Interleukin-1-mediated Autocrine Mechanism (2008)

Interleukin-1 (IL-1) and tumor necrosis factor (TNF) mediate bone resorption in a variety of diseases affecting bone. Like TNF, IL-1 is secreted by osteoclast precursors (OCPs), but unlike TNF, it does not induce osteoclast formation directly from OCPs in vitro. TNF induces IL-1 expression and activates c-Fos, a transcription factor required in OCPs for osteoclast formation. Here, we examined whether IL-1 can induce osteoclast formation directly from OCPs overexpressing c-Fos and whether interaction with bone matrix affects OCP cytokine expression. We infected OCPs with c-Fos or green fluorescent protein retrovirus, cultured them with macrophage colony-stimulating factor and IL-1 on bone slices or plastic dishes, and assessed osteoclast and resorption pit formation and expression of IL-1 by OCPs. We used a Transwell assay to determine whether OCPs secrete IL-1 when they interact with bone matrix. IL-1 induced osteoclast formation directly from c-Fos-expressing OCPs on plastic. c-Fos-expressing OCPs formed osteoclasts spontaneously on bone slices without addition of cytokines. OCPs on bone secreted IL-1, which induced osteoclast formation from c-Fos-expressing OCPs in the lower Transwell dishes. The bone matrix proteins dentin sialoprotein and osteopontin, but not transforming growth factor-beta, stimulated OCP expression of IL-1 and induced c-Fos-expressing OCP differentiation into osteoclasts. Osteoclasts eroding inflamed joints have higher c-Fos expression compared with osteoclasts inside bone. We conclude that OCPs expressing c-Fos may induce their differentiation directly into osteoclasts by an autocrine mechanism in which they produce IL-1 through interaction with bone matrix. TNF could induce c-Fos expression in OCPs at sites of inflammation in bone to promote this autocrine mechanism and thus amplify bone loss.
Sequence-Specific DNA Alkylation by Hybrid Molecules between Segment A of Duocarmycin A and Pyrrole/Imidazole Diamide (1999)

In the absence of distamycin A (Dist), hybrids 1 (X=N, CH) selectively alkylate the 3' end of adenine in AT-rich DNA sequences. However, these hybrids can form a heterodimer with Dist to alkylate G residues of predetermined DNA sequences efficiently and with high selectivity.
VOCACIÓN ONTOLÓGICA DE CARLOS FERNÁNDEZ SESSAREGO. APROXIMACIÓN AL ITINERARIO VITAL E INTELECTUAL DEL MAESTRO SANMARQUINO (2007)

Sumario: Introducción I. Estudios y formación sanmarquina II. Magisterio y vocación III. Estadía en Italia. Aporte civilista y jusfilosófico IV. Experiencia forense y política V. Aportes jusfilosóficos y jurídicos. Apuntes parciales V.1. La pregunta por el ser del Derecho. Itinerario de una investigación jusfilosófica V.2. Anticipación al planteamiento de Reale. Significado de la indagación de 1950 V.3. La pregunta sobre la persona. Relación con el Derecho.
COVNET: a cooperative coevolutionary model for evolving artificial neural networks (2003)

This paper presents COVNET, a new cooperative coevolutionary model for evolving artificial neural networks. This model is based on the idea of coevolving subnetworks that must cooperate to form a solution for a specific problem, instead of evolving complete networks. The combination of this subnetworks is part of a coevolutionary process. The best combinations of subnetworks must be evolved together with the coevolution of the subnetworks. Several subpopulations of subnetworks coevolve cooperatively and genetically isolated. The individual of every subpopulation are combined to form whole networks. This is a different approach from most current models of evolutionary neural networks which try to develop whole networks. COVNET places as few restrictions as possible over the network structure, allowing the model to reach a wide variety of architectures during the evolution and to be easily extensible to other kind of neural networks. The performance of the model in solving three real problems of classification is compared with a modular network, the adaptive mixture of experts and with the results presented in the bibliography. COVNET has shown better generalization and produced smaller networks than the adaptive mixture of experts and has also achieved results, at least, comparable with the results in the bibliography.
Changes to the Equine Hindgut Microflora in Response to Antibiotic Challenge (2012)

Antibiotics are important to equine medicine, but can cause detrimental side-effects including reduced feed intake, allergic reactions, and diarrhea. Antibiotic-associated diarrhea (AAD) is attributed to disruption of the hindgut microflora, permitting proliferation of pathogenic microbes. The objectives were to evaluate the effects of antibiotics on beneficial fecal bacteria, AAD-associated pathogens, microbial species richness and fermentation. Horses were assigned to treatment groups: control (no antibiotics, n=6), trimethoprim-sulfadiazine (oral, n=6), or sodium ceftiofur (IM, n=6). Fecal samples were taken during adaptation (3 wk), antibiotic challenge (1 wk), and withdrawal (1 wk). Fecal cellulolytics decreased by >99% during challenge and did not recover during withdrawal (P < 0.0001). Lactobacilli decreased by >60% during challenge (P = 0.0453). Salmonella spp. increased 94% with trimethoprim-sulfadiazine challenge (P = 0.0115). There was no detectable Clostridium difficile during adaptation or in any control horse. C. difficile increased (P < 0.0001) when horses were challenged, and remained elevated 7 d after withdrawal. There was no effect of challenge on in vitro digestibility or microbial species richness as evaluated by denaturing gradient gel electrophoresis (P > 0.05). These results indicate that antibiotics can disrupt the normal flora and allow proliferation of pathogens, even without affecting digestibility and causing AAD.
Phase Separation in an SiCO Glass Studied by Transmission Electron Microscopy and Electron Energy‐Loss Spectroscopy (2001)

SiCO glasses prepared from sol–gel precursors via pyrolysis in argon at temperatures ranging from 1000° to 1400°C were studied by transmission electron microscopy (TEM), in conjunction with electron energy‐loss spectroscopy (EELS). EELS analysis showed that stoichiometric SiCO glass underwent phase separation, forming SiO 2 ‐ and SiC‐based environments. This process started at ∼1200°C. However, at temperatures &gt;1300°C, precipitation of nanometer‐sized SiC particles embedded in vitreous SiO 2 was monitored by high‐resolution TEM.
A Mouse Model Of Adult Polyglucosan Body Disease (APBD), A Late Onset Variant Of Glycogen Storage Disease Type IV (GSD IV). (P1.054) (2014)

Objective: Generation and characterization of a mouse model of APBD with the most common mutation found in Adult Polyglucosan Body Disease (APBD, adult onset GSD IV) patients, substituting amino acid tyrosine with serine "Y329S" in glycogen branching enzyme (GBE1). Background: Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder caused by deficiency of the glycogen branching enzyme (GBE). The pathologic hallmark of the disease is the accumulation of a poorly branched form of glycogen known as polyglucosan (PG). The disease is clinically heterogeneous, with variable tissue involvement and age of onset. Absence of enzyme activity is lethal in utero or in infancy, affecting primarily muscle and liver. However, residual enzyme activity (5-20%) leads to a juvenile or adult-onset disorder that affects primarily muscle and both central and peripheral nervous systems. Design: Here, we describe a mouse model of GSD IV that reflects the adult form of this disease. Homologous recombination was used to insert the Y329S human mutation in exon 7 of the mouse Gbe1 leading to reduced GBE activity. Results: Mice bearing this mutation (Gbe1YS/YS) exhibit a phenotype similar to APBD, with wide spread accumulation of PG. In contrast, FLPe-mediated homozygous deletion of exon 7 abrogated GBE activity completely (Gbe1-/-), leading to a phenotype of lethal early-onset GSD IV. Adult mice with low GBE activity exhibit progressive neuromuscular dysfunction but live more than 18 months whereas mice (Gbe1neo/neo) with severely reduced GBE activity die prematurely. At difference from muscle, PG in liver is a degradable source of glucose and is readily depleted by fasting, emphasizing that there are structural and regulatory differences in glycogen metabolism among tissues. Conclusion: This mouse model recapitulates the typical histological and physiological features of the adult variant of human branching enzyme deficiency.
Abnormal melatonin response to 5-methoxypsoralen in dementia (1989)

The authors investigated the melatonin response to 5-methoxypsoralen in 39 healthy adult and elderly subjects and in 13 demented, 13 depressed, and 13 schizophrenic inpatients. Subjects' plasma melatonin levels were evaluated before they took single, oral 40-mg doses of 5-methoxypsoralen and 3 hours afterward. The preliminary results indicate that the melatonin response of the pineal gland to 5-methoxypsoralen is reduced in demented patients compared to that in healthy elderly subjects. Depressed and schizophrenic patients had a normal melatonin response to the drug. This finding suggests that the pineal gland may be functionally impaired in dementia but not in depression.
Cytokine Manipulation in Animal Models of Asthma (1997)

We have developed in C57 Black 6 mice an in vivo model of allergic airway inflammation characterized by the presence of IgE antibodies to an inhaled antigen, peribronchial infiltrates with an increased number of eosinophils, and an increased airway responsiveness to nonantigenic bronchoconstrictor stimuli. In this animal model we have investigated the role of different cytokines in the development of IgE antibodies to inhaled antigen, eosinophilic airway inflammation, and airway hyperresponsiveness. The studies were performed by using knockout mice or by exogenous administration of cytokines or cytokine antagonists. Interleukin-4 (IL-4) knockout mice were unable to develop an allergic eosinophilic airway infiltration and did not produce specific IgE antibodies. Chronic aerosol exposure to antigen also did not induce an increase in airway responsiveness. In studies of wild-type mice, pretreatment with the combination of anti-IL5 and anti-IL-5 receptor antibodies, given in an attempt to fully inhibit the effect of endogenously released IL-5, caused a pronounced inhibition of the antigen-induced airway eosinophilia but did not prevent the increase in airway responsiveness. Treatment with IL-12 during the active immunization prevented airway eosinophilia, production of specific IgE antibodies, and the antigen-induced increase in airway responsiveness. In contrast, administration of IL-12 to actively immunized mice during the aerosol exposure abolished airway eosinophilia and airway hyperresponsiveness without affecting the production of specific IgE.
Effects of the Conjugated Equine Estrogen/Bazedoxifene Tissue-Selective Estrogen Complex (TSEC) on Mammary Gland and Breast Cancer in Mice (2012)

A tissue-selective estrogen complex (TSEC), combining a selective estrogen receptor modulator, bazedoxifene (BZA), with conjugated equine estrogen (CEE), represents a novel strategy of menopausal hormone therapy without involving a progestin. We hypothesized that the antiestrogenic properties of BZA can also block the estrogenic effects of CEE on breast tissue and thereby prevent breast cancer in women. To test our hypothesis, the effects of estradiol (E(2)), CEE, and BZA on mammary gland and breast cancer xenografts were assessed in mouse models. In immature castrate mice, BZA completely blocked CEE- or E(2)-stimulated ductal and terminal end bud growth of mammary gland as well as estrogen-responsive gene expression. As a positive control, E(2) stimulated tumor growth in nude mice bearing MCF-7 xenografts. This effect was completely blocked by BZA as were E(2)-stimulated expression of PR, pS2 (trefoil factor 1), cMyc, and AREG; the enhancement of Ki67 and proliferating cell nuclear antigen (PCNA); and the antiapoptotic effect. CEE was much less potent than E(2) in stimulating Ki67, reducing apoptosis, and stimulating gene expression, but all effects were blocked by BZA. Unexpectedly, CEE alone, even at high doses, did not stimulate tumor growth. As confirmation of its absorption and deconjugation, CEE caused a 6-fold increase in uterine weight and stimulation of gene expression. These data support our hypothesis that the net effect of the CEE/BZA TSEC is to block estrogen action in benign and malignant breast tissue. These findings provide a rationale for a clinical study to determine whether this TSEC prevents breast cancer in women.
Atropisomers of Arylmaleimides: Stereodynamics and Absolute Configuration (2013)

4-Aryl-3-bromo-N-benzylmaleimides and 3,4-biaryl-N-benzylmaleimides have been synthesized by a modified Suzuki cross-coupling reaction from 3,4-dibromo-N-benzylmaleimide. The conformational studies by dynamic NMR and DFT calculations showed that the interconversion barrier between the two available skewed conformations is under steric control. When the aryl group was a 2-methylnaphthyl, thermally stable atropisomers were isolated by enantioselective HPLC and their absolute configurations were assigned by TD-DFT simulations of the ECD spectra.
Inhibition of Cellular Proliferation by the Wilms’ Tumor Suppressor WT1 Is Associated with Suppression of Insulin-Like Growth Factor I Receptor Gene Expression (1995)

We have investigated the regulation of the insulin-like growth factor I receptor (IGF-I-R) gene promoter by the Wilms' tumor suppressor WT1 in intact cells. The levels of endogenous IGF-I-R mRNA and the activity of IGF-I-R gene promoter fragments in luciferase reporter constructs were found to be significantly higher in G401 cells (a Wilms' tumor-derived cell line lacking detectable WT1 mRNA) than in 293 cells (a human embryonic kidney cell line which expresses significant levels of WT1 mRNA). To study whether WT1 could suppress the expression of the endogenous IGF-I-R gene, WT1-negative G401 cells were stably transfected with a WT1 expression vector. Expression of WT1 mRNA in G401 cells resulted in a significant decrease in the rate of cellular proliferation, which was associated with a reduction in the levels of IGF-I-R mRNA, promoter activity, and ligand binding and with a reduction in IGF-I-stimulated cellular proliferation, thymidine incorporation, and anchorage-independent growth. These data suggest that a major aspect of the action of the WT1 tumor suppressor is the repression of IGF-I-R gene expression.
I-SceI Endonuclease, a New Tool for Studying DNA Double-Strand Break Repair Mechanisms in Drosophila (1999)

As a step toward the development of a homologous recombination system in Drosophila, we have developed a methodology to target double-strand breaks (DSBs) to a specific position in the Drosophila genome. This method uses the mitochondrial endonuclease I-SceI that recognizes and cuts an 18-bp restriction site. We find that >6% of the progeny derived from males that carry a marker gene bordered by two I-SceI sites and that express I-SceI in their germ line lose the marker gene. Southern blot analysis and sequencing of the regions surrounding the I-SceI sites revealed that in the majority of the cases, the introduction of DSBs at the I-SceI sites resulted in the complete deletion of the marker gene; the other events were associated with partial deletion of the marker gene. We discuss a number of applications for this novel technique, in particular its use to study DSB repair mechanisms.
Kv7 Channels: Function, Pharmacology and Channel Modulators (2006)

K(v)7 channels are unique among K(+) channels, since four out of the five channel subtypes have well-documented roles in the development of human diseases. They have distinct physiological functions in the heart and in the nervous system, which can be ascribed to their voltage-gating properties. The K(v)7 channels also lend themselves to pharmacological modulation, and synthetic openers as well as blockers of the channels, regulating neuronal excitability, have existed even before the K(v)7 channels were identified by cloning. In the present review we give an account on the focused efforts to develop selective modulators, openers as well as blockers, of the K(v)7 channel subtypes, which have been undertaken during recent years, along with a discussion of the K(v)7 ion channel physiology and therapeutic indications for modulators of the neuronal K(v)7 channels.
Formulation, characterization and evaluation of rotavirus encapsulated PLA and PLGA particles for oral vaccination (2008)

Polylactide (PLA) and polylactide-co-glycolide (PLGA) particles entrapping rotavirus (strain SA11) were formulated using a solvent evaporation technique. To minimize denaturation of viral antigen during the emulsification process, serum albumin was used as a stabilizer. Use of NaHCO3 and sucrose during the primary emulsification step resulted in uniform stabilized particles entrapping rotavirus. Sonication during the primary emulsion and homogenization during the secondary emulsion process resulted in particles of sizes 2–8 μm, whereas nanoparticles were formed when sonication was used during both primary and secondary emulsion processes. Scanning electron and atomic force microscopy showed uniform pores and roughness throughout the polymer particle surface. Single dose oral immunization with 20 μg of antigen entrapped in PLA particles elicited improved and long-lasting IgA and IgG antibody titer in comparison to the soluble antigen. The study shows results illustrating the usefulness of polymeric microparticles as a potential oral delivery system for rotavirus vaccine.
Quantitation of Metal Content in the Silver-Assisted Growth of Gold Nanorods (2006)

The seed-mediated approach to making gold nanorods in aqueous surfactant solutions has become tremendously popular in recent years. Unlike the use of strong chemical reductants to make spherical gold nanoparticles, the growth of gold nanorods requires weak reducing conditions, leading to an unknown degree of gold reduction. The metal content of gold nanorods, made in high yield in the presence of silver ion, is determined by inductively coupled plasma atomic emission spectroscopy. Through the use of the known gold concentration in nanorods, molar extinction coefficients are calculated for nanorods of varying aspect ratios from 2.0 to 4.5. The extinction coefficients at the longitudinal plasmon band peak maxima for these nanorods vary from 2.5x10(9) to 5.5x10(9) M-1 cm-1, respectively, on a per-particle basis. Many of the gold ions present in the growth solution remain unreacted; insights into the growth mechanism of gold nanorods are discussed.
Safety and efficacy of a mutagen-attenuated Rift Valley fever virus vaccine in cattle (1997)

RVF MP-12 may be safe and efficacious for use in pregnant or lactating bovids, and a minimal dose of vaccine may provide suitable protection against viremia.