gebhart/patrepeval huggingface dataset:
Stereotypic culture systems for liver and bone marrow: Evidence for the development of functional tissue in vitro and following implantation in vivo (1994)

Stromal cell-associated liver cell and bone marrow (BM) culture on three-dimensional nylon screen or polyglycolic acid (PGA) felt templates conveys certain functional advantages to the parenchyma of these tissues. Hepatic parenchymal cells (PC) manifest long-term ( approximately 2 month) expression of liver-specific activities including cytochrome P450 enzyme activity and the synthesis of albumin, fibrinogen, transferrin, and other proteins. PC also undergo proliferation in association with stromal cells that were pre-established on these templates. PC mitoses are directly proportional to available space within the template for their expansion indication that geometric or sterotypic parameters influence the growth of these cells in vitro. BM cultured on a similar template exhibits long-term multilineage hematopoietic expression and limited expansion of progenitor cell numbers. Progenitor cell concentration within the cultures can be substantially enhanced if these cells are liberated from co-culture and reseeded onto a template containing fresh stromal cells. BM and liver cel cultures established on felt composed of bioresorbable PGA filaments was grafted into various sites in rats. Liver co-cultures generated sinusoids and other liver-like structures in situ; active hematopoietic blasts were observed at sites of BM co-culture grafts. Biodegradable polymer constructs may prove useful for certain clinical applications as vehicles for the delivery of tissues that were engineered in culture.
Relación del VO2 máx. medido con el test de Naveta, niveles de atención y el rendimiento académico en estudiantes de 10 a 13 años de un colegio de Santiago de Chile (2015)

El objetivo de la presente investigacion es conocer la relacion entre el consumo maximo de oxigeno, la atencion y el rendimiento academico en estudiantes de ensenanza basica. La muestra estuvo constituida por 91 escolares con edades entre 10 y 13 anos de un colegio de Santiago. Se determino el VO2 max. de forma indirecta a traves del test Naveta, para la atencion se aplico el test de Toulouse-Pieron y las notas se obtuvieron con las actas de calificaciones de los alumnos. Los resultados muestran que no existe relacion entre el VO2 max. y la atencion. Tampoco hay relacion del VO2 max. con los promedios de lenguaje, matematica, ciencias naturales e historia. Son necesarias mas investigaciones con muestras de mayor tamano que aumente la variabilidad del consumo de oxigeno para relacionarlo con otras variables que afectan el aprendizaje.
Polymeric micelles for oral drug delivery: Why and how (2004)

Abstract The oral delivery of drugs is regarded as the optimal means for achieving therapeutic effects owing to increased patient compliance. Unfortunately, the oral delivery route is beset with problems such as gastrointestinal (GI) destruction of labile molecules, low levels of macromolecular absorption, etc. To reduce the impact of digestive enzymes and to ensure the absorption of bioactive agents in an unaltered form, molecules may be incorporated into microparticulate carriers. Many approaches to achieve the oral absorption of a wide variety of drugs are currently under investigation. Among the different polymer-based drug delivery systems, polymeric micelles represent a promising delivery vehicle especially intended for poorly water-soluble pharmaceutical active ingredients in order to improve their oral bioavailability. Recent findings of a dextran-based polymeric micelle study for solubilization of a highly lipophilic drug, cyclosporin A (CsA), will be discussed.
The Effect of Shape and Distribution of Perforations on Squeeze-Film Damping in Parallel Plate Capacitors (2009)

The effect of the shape and distribution of perforations in parallel plate capacitive MEMS devices on squeeze-film damping is presented. The squeeze film effect is the most important damping effect on the dynamic behavior of most MEMS devices that employ capacitive sensing and actuation, which typically employ narrow air gaps between planar moving surfaces [1, 2]. The stationary plate of a capacitive device is often perforated to reduce the damping and sensor noise and improve the frequency response. The formula for determining the total viscous damping in the gap contains a coefficient Cp that is associated with the geometry and distribution of the holes on the stationary plate. In this study, the coefficient Cp is determined using the finite element method using ANSYS by analogy with heat conduction in a solid with internal heat generation. Round, elliptical, rectangular, and oval holes that are distributed either aligned or offset are analyzed and compared. It is shown that the surface fraction occupied by the perforations is not the only factor that determines Cp. Both the shape and distribution strongly affect the damping coefficient [3, 4]. By using elongated perforations that are properly distributed, the squeeze film damping could be minimized with the minimum amount of perforation. The analysis performed in this work is quite general being applicable to a very large spectrum of frequencies and to various fluids in capacitive sensors. These results can facilitate the design of mechanical structures that utilize capacitive sensing and actuation, such as accelerometers, optical switches, micro-torsion mirrors, resonators, microphones, etc.
Comparing Pooled Peptides with Intact Protein for Accessing Cross-presentation Pathways for Protective CD8+ and CD4+ T Cells (2009)

To better understand the mechanisms of intracellular trafficking and presentation of exogenous peptides by antigen-presenting cells (APC), we compared the handling of overlapping 24-mer peptides from HIV Nef either mixed or covalently linked in tandem in one protein. Once internalized, peptides trafficked not only to endosomes but also to cytosol, and activated CD8(+) and CD4(+) T cells. In contrast, whole protein was found to traffic only to the endosomal compartments, and primarily activated CD4(+) T cells. Finally, with adjuvant, overlapping peptides were capable of protecting against lethal viral challenge, whereas the intact protein was less protective. These data suggest that overlapping long peptides are cross-presented through more varied intracellular routes and are more efficient in priming protective immunity than the whole protein.
Effects of Metformin, Buformin, and Phenformin on the Post-Initiation Stage of Chemically Induced Mammary Carcinogenesis in the Rat (2015)

Metformin is a widely prescribed drug for the treatment of type II diabetes. Although epidemiologic data have provided a strong rationale for investigating the potential of this biguanide for use in cancer prevention and control, uncertainty exists whether metformin should be expected to have an impact in nondiabetic patients. Furthermore, little attention has been given to the possibility that other biguanides may have anticancer activity. In this study, the effects of clinically relevant doses of metformin (9.3 mmol/kg diet), buformin (7.6 mmol/kg diet), and phenformin (5.0 mmol/kg diet) were compared with rats fed control diet (AIN93-G) during the post-initiation stage of 1-methyl-1-nitrosourea-induced (50 mg/kg body weight) mammary carcinogenesis (n = 30/group). Plasma, liver, skeletal muscle, visceral fat, mammary gland, and mammary carcinoma concentrations of the biguanides were determined. In comparison with the control group, buformin decreased cancer incidence, multiplicity, and burden, whereas metformin and phenformin had no statistically significant effect on the carcinogenic process relative to the control group. Buformin did not alter fasting plasma glucose or insulin. Within mammary carcinomas, evidence was obtained that buformin treatment perturbed signaling pathways related to energy sensing. However, further investigation is needed to determine the relative contributions of host systemic and cell autonomous mechanisms to the anticancer activity of biguanides such as buformin.
Retinoic Acid Increases Foxp3+ Regulatory T Cells and Inhibits Development of Th17 Cells by Enhancing TGF-β-Driven Smad3 Signaling and Inhibiting IL-6 and IL-23 Receptor Expression (2008)

The de novo generation of Foxp3+ regulatory T (Treg) cells in the peripheral immune compartment and the differentiation of Th17 cells both require TGF-beta, and IL-6 and IL-21 are switch factors that drive the development of Th17 cells at the expense of Treg cell generation. The major vitamin A metabolite all-trans retinoic acid (RA) not only enforces the generation of Treg cells but also inhibits the differentiation of Th17 cells. Herein we show that RA enhances TGF-beta signaling by increasing the expression and phosphorylation of Smad3, and this results in increased Foxp3 expression even in the presence of IL-6 or IL-21. RA also inhibits the expression of IL-6Ralpha, IRF-4, and IL-23R and thus inhibits Th17 development. In vitro, RA significantly promotes Treg cell conversion, but in vivo during the development of experimental autoimmune encephalomyelitis it does not increase the frequency of Treg cells in the face of an ongoing inflammation. However, RA suppresses the disease very efficiently by inhibiting proinflammatory T cell responses, especially pathogenic Th17 responses. These data not only identify the signaling mechanisms by which RA can affect both Treg cell and Th17 differentiation, but they also highlight that in vivo during an autoimmune reaction, RA suppresses autoimmunity mainly by inhibiting the generation of effector Th17 cells.
What is left when anti-tumour necrosis factor therapy in inflammatory bowel diseases fails? (2014)

The inflammatory bowel diseases (IBDs) are chronic incurable conditions that primarily present in young patients. Being incurable, the IBDs may be part of the patient's life for many years and these conditions require therapies that will be effective over the long-term. Surgery in Crohn's disease does not cure the disease with endoscopic recurrent in up to 70% of patients 1 year post resection. This means that, the patient will require many years of medications and the goal of the treating physician is to induce and maintain long-term remission without side effects. The development of the anti-tumour necrosis factor alpha (TNFα) agents has been a magnificent clinical advance in IBD, but they are not always effective, with loss of response overtime and, at times, discontinuation is required secondary to side effects. So what options are available if of the anti-TNFα agents can no longer be used? This review aims to provide other options for the physician, to remind them of the older established medications like azathioprine/6-mercaptopurine and methotrexate, the less established medications like mycophenolate mofetil and tacrolimus as well as newer therapeutic options like the anti-integins, which block the trafficking of leukocytes into the intestinal mucosa. The location of the intestinal inflammation must also be considered, as topical therapeutic agents may also be worthwhile to consider in the long-term management of the more challenging IBD patient. The more options that are available the more likely the patient will be able to have tailored therapy to treat their disease and a better long-term outcome.
Atomic Resolution (0.98 Å) Structure of Eosinophil-Derived Neurotoxin, (2002)

Human eosinophil-derived neurotoxin (EDN) is a small, basic protein that belongs to the ribonuclease A superfamily. EDN displays antiviral activity and causes the neurotoxic Gordon phenomenon when injected into rabbits. Although EDN and ribonuclease A have appreciable structural similarity and a conserved catalytic triad, their peripheral substrate-binding sites are not conserved. The crystal structure of recombinant EDN (rEDN) has been determined at 0.98 A resolution from data collected at a low temperature (100 K). We have refined the crystallographic model of the structure using anisotropic displacement parameters to a conventional R-factor of 0.116. This represents the highest resolution structure of rEDN determined to date and is only the second ribonuclease structure to be determined at a resolution greater than 1.0 A. The structure provides a detailed picture of the conformational freedom at the various subsites of rEDN, and the water structure accounts for more than 50% of the total solvent content of the unit cell. This information will be crucial for the design of tight-binding inhibitors to restrain the ribonucleolytic activity of rEDN.
Reaction of myoglobin with phenylhydrazine: a molecular doorstop (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReaction of myoglobin with phenylhydrazine: a molecular doorstopDagmar Ringe, Gregory A. Petsko, David E. Kerr, and Paul R. Ortiz de MontellanoCite this: Biochemistry 1984, 23, 1, 2–4Publication Date (Print):January 3, 1984Publication History Published online1 May 2002Published inissue 3 January 1984https://pubs.acs.org/doi/10.1021/bi00296a001https://doi.org/10.1021/bi00296a001research-articleACS PublicationsRequest reuse permissionsArticle Views226Altmetric-Citations175LEARN 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
A method for directed evolution and functional cloning of enzymes (1998)

A general scheme is described for the in vitro evolution of protein catalysts in a biologically amplifiable system. Substrate is covalently and site specifically attached by a flexible tether to the pIII coat protein of a filamentous phage that also displays the catalyst. Intramolecular conversion of substrate to product provides a basis for selecting active catalysts from a library of mutants, either by release from or attachment to a solid support. This methodology has been developed with the enzyme staphylococcal nuclease as a model. An analysis of factors influencing the selection efficiency is presented, and it is shown that phage displaying staphylococcal nuclease can be enriched 100-fold in a single step from a library-like ensemble of phage displaying noncatalytic proteins. Additionally, this approach should allow one to functionally clone natural enzymes, based on their ability to catalyze specific reactions (e.g., glycosyl transfer, sequence-specific proteolysis or phosphorylation, polymerization, etc.) rather than their sequence- or structural homology to known enzymes.
Oxysterols are substrates for cholesterol sulfotransferase (2007)

Oxysterols constitute a class of cholesterol derivatives that exhibit broad biological effects ranging from cytotoxicity to regulation of nuclear receptors. The role of oxysterols such as 7-ketocholesterol (7-KC) in the development of retinal macular degeneration and atheromatous lesions is of particular interest, but little is known of their metabolic fate. We establish that the steroid/sterol sulfotransferase SULT2B1b, known to efficiently sulfonate cholesterol, also effectively sulfonates a variety of oxysterols, including 7-KC. The cytotoxic effect of 7-KC on 293T cells was attenuated when these cells, which do not express SULT2B1b, were transfected with SULT2B1b cDNA. Importantly, protection from 7-KC-induced loss of cell viability with transfection correlated with the synthesis of SULT2B1b protein and the production of the 7-KC sulfoconjugate (7-KCS). Moreover, when 7-KCS was added to the culture medium of 293T cells in amounts equimolar to 7-KC, no loss of cell viability occurred. Additionally, MCF-7 cells, which highly express SULT2B1b, were significantly more resistant to the cytotoxic effect of 7-KC. We extended the range of oxysterol substrates for SULT2B1b to include 7alpha/7beta-hydroxycholesterol and 5alpha,6alpha/5beta,6beta-epoxycholesterol as well as the 7alpha-hydroperoxide derivative of cholesterol. Thus, SULT2B1b, by acting on a variety of oxysterols, offers a potential pathway for modulating in vivo the injurious effects of these compounds.
Zinc-ion binding and cytokine activity regulation pathways predicts outcome in relapsing–remitting multiple sclerosis (2007)

Multiple sclerosis (MS) is a demyelinating disease characterized by an unpredictable clinical course with intermittent relapses that lead over time to significant neurological disability. Clinical and radiological variables are limited in the ability to predict disease course. Peripheral blood genome scale analyses were used to characterize MS patients with different disease types, but not for prediction of outcome. Using complementary-DNA microarrays we studied peripheral-blood gene expression patterns in 53 relapsing-remitting MS patients. Patients were classified into good, intermediate and poor clinical outcome established after 2-year follow-up. A training set of 26 samples was used to identify clinical outcome differentiating gene-expression signature. Supervised learning and feature selection algorithms were applied to identify a predictive signature that was validated in an independent group of 27 patients. Key genes within the predictive signature were confirmed by quantitative reverse transcription-polymerase chain reaction in an additional 10 patients. The analysis identified 431 differentiating genes between patients with good and poor clinical outcome (change in neurological disability by the expanded disability status scale was -0.33 +/- 0.24 and 1.6 +/- 0.35, P = 0.0002, total number of relapses were 0 and 1.80 +/- 0.35, P = 0.00009, respectively). An optimal set of 29 genes was depicted as a clinical outcome predictive gene expression signature and classified appropriately 88.9% of patients. This predictive signature was enriched by genes related biologically to zinc-ion binding and cytokine activity regulation pathways involved in inflammation and apoptosis. Our findings provide a basis for monitoring patients by prediction of disease outcome and can be incorporated into clinical decision-making in relapsing-remitting MS.
Recombinant collagen production optimization in Escherichia coli (2005)

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.
ErbB2 and NFκB Overexpression as Predictors of Chemoradiation Resistance and Putative Targets to Overcome Resistance in Muscle-Invasive Bladder Cancer (2011)

Radical cystectomy for muscle-invasive bladder cancer (MIBC) patients frequently impairs their quality of life (QOL) due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR) to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS) were investigated. Of the 35 patients, 11 (31%) achieved pathological CR, while tumors in the remaining 24 patients (69%) were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014), 15.4 (P = 0.024) and 14.3 (P = 0.038). The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001). The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056) along with chemoradiation resistance (P = 0.003) and hydronephrosis (P = 0.018). The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with chemoradiation-resistant disease was 61% (P = 0.018). Thus, erbB2 and NFκB overexpression are relevant to chemoradiation resistance and are putative targets aimed at overcoming chemoradiation resistance in MIBC.
Fundamental research on surface modification of nano-size silica for underfill applications (2004)

In order to improve the rheological behavior of the nanosilica composite no-flow underfill, a filler surface treatment using silane coupling agents was investigated to reduce the filler-filler interaction and to achieve monodispersity of the nanosilica in the underfill resin. The experimental conditions of the surface treatment were investigated in a design of experiment (DOE) in terms of the pre-treatment methods, coupling agent types, concentrations, and treatment durations. The particle dispersion after treatment was evaluated by laser particle analyzer and transmission electron microscopy (TEM). A monodispersed nanosilica solution in the polar medium was achieved using optimal conditions. The surface chemistry of the nanosilica was studied using Fourier transformed infrared spectroscopy (FTIR). The wettability of underfill resin and water on the silane treated glass slides was studied using a goniometer. Based on the investigations, the silane-treated nanosilica fillers were incorporated into an underfill resin to formulate a nanocomposite no-flow underfill. It was found that the proper filler treatment could significantly reduce the viscosity of the nanocomposite.
A Phase I trial of 90Y-anti-carcinoembryonic antigen chimeric T84.66 radioimmunotherapy with 5-fluorouracil in patients with metastatic colorectal cancer. (2003)

Results from this trial are encouraging and demonstrate the feasibility and possible advantages of combining continuous infusion 5-FU with 90Y-cT84.66 RIT. The addition of 5-FU does not appear to significantly enhance hematological toxicities of the radiolabeled antibody. In addition, 5-FU reduces the development of human anti-chimeric antibody response, permitting multicycle therapy in a larger number of patients. Future efforts should continue to focus on integrating radiation therapy delivered by radiolabeled antibodies into established 5-FU regimens.