gebhart/patrepeval huggingface dataset:
The Diabetes Prevention Program. Design and methods for a clinical trial in the prevention of type 2 diabetes. (1999)

The Diabetes Prevention Program is a randomized clinical trial testing strategies to prevent or delay the development of type 2 diabetes in high-risk individuals with elevated fasting plasma glucose concentrations and impaired glucose tolerance. The 27 clinical centers in the U.S. are recruiting at least 3,000 participants of both sexes, approximately 50% of whom are minority patients and 20% of whom are > or = 65 years old, to be assigned at random to one of three intervention groups: an intensive lifestyle intervention focusing on a healthy diet and exercise and two masked medication treatment groups--metformin or placebo--combined with standard diet and exercise recommendations. Participants are being recruited during a 2 2/3-year period, and all will be followed for an additional 3 1/3 to 5 years after the close of recruitment to a common closing date in 2002. The primary outcome is the development of diabetes, diagnosed by fasting or post-challenge plasma glucose concentrations meeting the 1997 American Diabetes Association criteria. The 3,000 participants will provide 90% power to detect a 33% reduction in an expected diabetes incidence rate of at least 6.5% per year in the placebo group. Secondary outcomes include cardiovascular disease and its risk factors; changes in glycemia, beta-cell function, insulin sensitivity, obesity, diet, physical activity, and health-related quality of life; and occurrence of adverse events. A fourth treatment group--troglitazone combined with standard diet and exercise recommendations--was included initially but discontinued because of the liver toxicity of the drug. This randomized clinical trial will test the possibility of preventing or delaying the onset of type 2 diabetes in individuals at high risk.
Active Control of Low-Frequency Sound Radiation From Vibrating Panel Using Planar Sound Sources (2001)

Active control of low frequency sound radiation using planar secondary sources is theoretically investigated in this paper. The primary sound field originates from a vibrating panel and the planar sources are modeled as simply supported rectangular panels in an infinite baffle. The sound power of the primary and secondary panels are calculated using a near field approach, and then a series of formulas are derived to obtain the optimum reduction in sound power based on minimization of the total radiate sound power. Finally, active reduction for a number of secondary panel arrangements is examined and it is concluded that when the modal distribution of the secondary panel does not coincide with that of the primary panel, one secondary panel is sufficient. Otherwise four secondary panels can guarantee considerable reduction in sound power over entire frequency range of interest.
Efficient wideband linear arrays for imaging and therapy (2003)

Focused ultrasound surgery has typically been investigated with a large aperture single element dish, or narrowband transducer array, both of which preclude good ultrasound imaging. However, guidance is essential for effective therapy. The goal of this work was to develop linear arrays that have both the high transmit efficiency needed for therapy, yet the wide bandwidth associated with transducers for modern imaging systems. The authors present analysis and measurements on linear array transducers from 3 to 6 MHz, with measured transmit efficiencies up to 90 percent and pulse-echo fractional bandwidths of 45 to 65 percent. Power measurements on a 3.2 MHz, 5/spl times/5.5 mm linear array revealed unfocused continuous acoustic output in excess of 30 watts at greater than 80% efficiency while retaining the array's performance. Human scanning results and ultrasound imaging of phantoms is shown, as well as in vitro lesion formation with the 32 to 64 element arrays. By combining these features into one transducer, several benefits result, including real time electronic imaging, therapy and monitoring, lack of spatial misregistration, low cost, multiple-frequency imaging/therapy and the power of acoustic beamforming techniques. The high efficiency allows the transducer to be small in size, enables endoscopic and catheter-based procedures, provides close access to the region of interest with less intervening tissue layers, supports higher frequencies, and yields better spatial resolution for imaging and therapy. The results of the study can help guide the design of such systems.
Protective immunity against malaria liver stage after vaccination with live parasites (2008)

Despite nearly 100 years of research and control efforts, malaria remains one of the most important infectious diseases. An efficient vaccine would be a powerful to tool to reduce mortality and morbidity. Experimentally, induction of sterile immunity in humans after vaccination with attenuated sporozoites has been obtained. This observation has spurred the search for subunit vaccines that aim to reproduce this protection. As yet none of the current candidate subunit vaccines achieved complete protection reproducibly. This failure coupled to the recent advent of genetically modified Plasmodium parasites has led to a renewed interest in the use of live parasites for vaccination against malaria pre-erythrocytic stages. In this article, we review and discuss the recent developments in this field.
Modulation of CGRP-Induced Light Aversion in Wild-Type Mice by a 5-HT<sub>1B/D</sub>Agonist (2012)

The neuropeptide calcitonin gene-related peptide (CGRP) plays a critical role in the pathophysiology of migraine. We have focused on the role of CGRP in photophobia, which is a common migraine symptom. We previously used an operant-based assay to show that CGRP-sensitized transgenic (nestin/hRAMP1), but not control, mice exhibited light aversion in response to an intracerebroventricular CGRP injection. A key question was whether the transgenic phenotype was due to overexpression of the CGRP receptor at endogenous or novel expression sites. We reasoned that if endogenous receptor sites were sufficient for light-aversive behavior, then wild-type mice should also show the phenotype when given a sufficiently strong stimulus. In this study, we report that mice with normal levels of endogenous CGRP receptors demonstrate light avoidance following CGRP administration. This phenotype required the combination of two factors: higher light intensity and habituation to the testing chamber. Control tests confirmed that light aversion was dependent on coincident exposure to CGRP and light and cannot be fully explained by increased anxiety. Furthermore, CGRP reduced locomotion only in the dark, not in the light. Coadministration of rizatriptan, a 5-HT(1B/D) agonist anti-migraine drug, attenuated the effects of exogenous CGRP on light aversion and motility. This suggests that triptans can act by mechanisms that are distinct from inhibition of CGRP release. Thus, we demonstrate that activation of endogenous CGRP receptors is sufficient to elicit light aversion in mice, which can be modulated by a drug commonly used to treat migraine.
How to overcome (and exploit) tumor hypoxia for targeted gene therapy (2003)

Tumor hypoxia has long been recognized as a critical issue in oncology. Resistance of hypoxic areas has been shown to affect treatment outcome after radiation, chemotherapy, and surgery in a number of tumor sites. Two main strategies to overcome tumor hypoxia are to increase the delivery of oxygen (or oxygen-mimetic drugs), and exploiting this unique environmental condition of solid tumors for targeted therapy. The first strategy includes hyperbaric oxygen breathing, the administration of carbogen and nicotinamide, and the delivery of chemical radiosensitizers. In contrast, bioreductive drugs and hypoxia-targeted suicide gene therapy aim at activating cytotoxic agents at the tumor site, while sparing normal tissue from damage. The cellular machinery responds to hypoxia by activating the expression of genes involved in angiogenesis, anaerobic metabolism, vascular permeability, and inflammation. In most cases, transcription is initiated by the binding of the transcription factor hypoxia-inducible factor (HIF) to hypoxia responsive elements (HREs). Hypoxia-targeting for gene therapy has been achieved by utilizing promoters containing HREs, to induce selective and efficient transgene activation at the tumor site. Hypoxia-targeted delivery and prodrug activation may add additional levels of selectivity to the treatment. In this article, the latest developments of cancer gene therapy of the hypoxic environment are discussed, with particular attention to combined protocols with ionizing radiation. Ultimately, it is proposed that by adopting specific transgene activation and molecular amplification systems, resistant hypoxic tumor tissues may be effectively targeted with gene therapy.
Active-Power Control of Individual Converter Cells for a Battery Energy Storage System Based on a Multilevel Cascade PWM Converter (2010)

The battery energy storage system is an essential enabling device of the smart grid, because it helps grid connection of massive renewable energy resources. This paper has a brief discussion on a battery energy storage system based on a multilevel cascade pulsewidth-modulated (PWM) converter for its practical use. The active-power control of individual converter cells is presented to make it possible to charge and discharge the battery units at different power levels while producing a three-phase balanced line-to-line voltage. This results in the maximum utilization of battery energy even when the power-handling capabilities of the battery units differ. Experimental results obtained from a 200-V, 10-kW, 3.6-kWh battery energy storage system verify the effectiveness of the presented active-power control.
Control of the γ-alumina to α-alumina phase transformation for an optimized alumina densification (2016)

In this work, we studied the aptitude to sintering green bodies using γ-Al2O3 transition alumina as raw powder. We focused on the influence of the heating rate on densification and microstructural evolution. Phase transformations from transition alumina γ → δ → θ → α-Al2O3 were studied by in situ X-rays diffraction from the ambient to 1200 °C. XRD patterns revealed coexistence of various phase transformations during the heating cycle. DTA and dilatometry results showed that low heating rate leads to a significant reduction of the temperature of the α-Al2O3 alumina formation. Around 1190, 1217 and 1240 °C were found when using 5, 10 and 20 °C/min of heating rate, respectively. The activation energy for θ-Al2O3 → α-Al2O3 transformation calculated by Kissinger and JMA equations using dilatometry method were 464.29 and 488.79 kJ/mol, respectively and by DTA method were 450.72 and 475.49 kJ/mol, respectively. In addition, the sintering of the green bodies with low heating rate promotes the rearrangement of the grains during θ-Al2O3 → α-Al2O3 transformation, enhancing the relative density to 95% and preventing the development of a vermicular structure. En este trabajo, se ha estudiado la capacidad de sinterización de muestras en verde a partir de γ-Al2O3 de transición en forma de polvo. El trabajo se ha focalizado en la influencia de la velocidad de calentamiento sobre la densificación y la evolución microestructural. Las transformaciones de fase de alúminas de transición γ→δ→θ→α-Al2O3 se han estudiado in situ mediante Difracción de Rayos X (DRX) desde temperatura ambiente hasta 1.200 °C. Los diagramas de XRD han revelado la coexistencia de diversas transformaciones de fase durante el ciclo de calentamiento. Los Análisis Térmicos Diferenciales (ATD) realizados y los datos de dilatometría han mostrado que velocidades de calentamiento bajas conducen a una reducción significativa de la temperatura de formación de α-Al2O3. Detectándose alrededor de 1.190, 1.217 y 1.240 °C cuando se utilizan 5, 10 y 20 °C/min como velocidad de calentamiento, respectivamente. La Energía de Activación para la transformación θ-Al2O3→α-Al2O3 calculada mediante las ecuaciones de Kissinger y JMA usando métodos dilatometricos han sido 464,29 y 488,79 kJ/mol, respectivamente, y mediante ATD 450,72 y 475,49 kJ/mol, respectivamente. Además, la sinterización con velocidad de calentamiento baja promueve la reorganización de los granos durante la transformación θ-Al2O3 → α-Al2O3, el aumento de la densidad relativa al 95% y la prevención del desarrollo de una estructura vermicular.
A 22-kd surface antigen detected by monoclonal antibody E 48 is exclusively expressed in stratified squamous and transitional epithelia. (1990)

After immunization of mice with viable cells of a metastasis of a laryngeal squamous cell carcinoma, a monoclonal antibody E 48 was obtained that detects an epitope present exclusively in squamous and transitional epithelium and their neoplastic counterparts. Immunoblotting revealed that E 48 recognizes a 22 kd molecule. Seventy-five of 76 squamous cell carcinomas from the head and neck, lung, cervix, and skin stained positively, whereas various adenocarcinomas from the colon, lung, and breast, and small cell lung carcinomas consistently stained negatively. The E 48 antigen, which is formaldehyde resistant, appears to be a reliable marker for differentiation of squamous cell carcinomas from adenocarcinoma, and small cell carcinomas.
Effect of microfluidization parameters on the physical properties of PEG-PLGA nanoparticles prepared using high pressure microfluidization (2008)

The objective of this work was to develop uniformly distributed poly(ethylene glycol) grafted poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles of mean size range approximately 100-200 nm using ethyl acetate as the solvent. In the multiple emulsion solvent evaporation method a high pressure microfluidization process was adopted to produce the W/O/W multiple emulsion. Non-toxic ethyl acetate was used to solubilize PEG-PLGA. The mean size of nanoparticles obtained was less than 180 nm. The particle size and size distribution were dependent on the microfluidization conditions applied. Mean particle size steadily increased from 121 nm at three passes to 172 nm at 20 passes of the microfluidizer, indicating that over-processing may be detrimental to PEG-PLGA nanoparticles prepared using this technique. There was no significant alteration of the PEG-PLGA matrix, as evidenced from the differential scanning calorimetric studies.
The structure of tautomycetin, a dialkylmaleic anhydride antibiotic. (1990)

The chemical structure of tautomycetin (C33H50O10) was determined by chemical degradation and spectroscopic evidence. Tautomycetin exists in methanol-buffer solution (1% diethylamine-formic acid, pH 7.3) as an equilibrium mixture of a 2,3-dialkylmaleic anhydride and its dicarboxylic acid. The structure of tautomycetin is similar to tautomycin in many respects.
Therapies under investigation for treating Parkinson's disease psychosis (2014)

Parkinson’s disease (PD) psychosis is a distressing condition that affects up to 60% of patients at the advanced stages of the disease. It significantly impairs patients’ and caregiver’s quality of life. Current therapeutic options are limited, and only clozapine and, more recently, pimavanserin were demonstrated to be effective in Phase III clinical trials. Phase II studies, open-label trials, case series and case reports have suggested an anti-psychotic efficacy of donepezil, melperone, mianserin, mirtazapine, ondansetron, quetiapine, rivastigmine and sarcosine. In contrast, aripiprazole, galantamine and memantine do not appear effective to alleviate PD psychosis. This review article discusses some of the available therapies to treat PD psychosis and surveys drugs that have recently undergone investigation, or that are presently being studied to address this condition.
Characterization of the inducible polyamine transporter in bovine lymphocytes (1988)

The polyamine uptake system in bovine lymphocytes was activated by concanavalin A. The system was common to putrescine, spermidine and spermine. The K t values for uptake activities of putrescine, spermidine and spermine were 3.7 uM, 0.38 uM and 0.23 uM in that order. The uptake activity was inhibited by carbonyl cyanide m ‐chlorophenylhydrazone, gramicidin D or valinomycin in the presence of 20 mM K + suggesting that polyamine uptake depends on the membrane potential. The uptake activity appeared 10 h after addition of concanavalin A, and the maximum was reached at 28 h indicating that induction of the polyamine transporter precedes the initiation of DNA synthesis. Addition of polyamine antimetabolites, such as α‐difluoromethyl‐ornithine and ethylglyoxal bis(guanylhydrazone), to the medium enhanced at least eightfold the induction of the polyamine transporter. The induction was repressed by addition of 50 uM spermidine or spermine, but not putrescine. We propose here that the induction of the membrane‐potential‐dependent polyamine transporter is regulated by the intracellular level of spermidine and spermine.
Dynamic Isolation and Unloading of Target Proteins by Aptamer-Modified Microtransporters (2011)

We describe here a new strategy for isolating target proteins from complex biological samples based on an aptamer-modified self-propelled microtube engine. For this purpose, a thiolated thrombin or a mixed thrombin-ATP aptamer (prehybridized with a thiolated short DNA) was coassembled with mercaptohexanol onto the gold surface of these microtube engines. The rapid movement of the aptamer-modified microtransporter resulted in highly selective and rapid capture of the target thrombin, with an effective discrimination against a large excess of nontarget proteins. Release of the captured thrombin can be triggered by the addition of ATP that can bind and displace the immobilized mixed thrombin-ATP aptamer in 20 min. The rapid loading and unloading abilities demonstrated by these selective microtransporters are illustrated in complex matrixes such as human serum and plasma. The new motion-driven protein isolation platform represents a new approach in bioanalytical chemistry based on active transport of proteins and offers considerable promise for diverse diagnostic applications.
Phase I evaluation of a synthetic mutant of beta-interferon. (1985)

A synthetic mutant of beta-interferon, produced by recombinant DNA technology, was prepared with serine substituted for the naturally occurring cysteine at amino acid 17. This molecule, after purification to homogeneity, was evaluated in 23 patients with cancer for tolerated doses, safety, and pharmacokinetics. Each patient was begun on twice weekly administration, one dose i.m., then an identical dose i.v. Doses, escalated weekly, were tolerated by 9 of 12 patients at 100 X 10(6) units i.m., 11 of 14 patients at 100 X 10(6) units i.v., and 8 of 10 patients receiving i.v. doses of 200 X 10(6) units. Fever (greater than or equal to 38.9 degrees C), the commonest cause for ceasing dose escalation, occurred in 11 of 13 patients who developed limiting i.v. toxicity and 6 of 11 who developed limiting i.m. toxicity. Patients who did not have progressive cancer after completion of dose escalation received five consecutive daily doses at their maximum tolerated single dose by each route, i.m. and i.v. These two 5-day treatments were given without difficulty. All patients treated with 300 X 10(6) units or less, i.m. (n = 13) or i.v. (n = 10), were able to receive five daily doses without limiting toxicity. Peak serum titers occurred immediately after i.v. administration and declined in an exponential manner thereafter. Despite absence of measurable titers in serum after i.m. injection, fever and significant (P less than 0.05) depression of WBC and platelet counts, serum calcium, and serum cholesterol occurred (prestudy to maximum tolerated dose). An immunoglobulin antibody to beta-interferon, detected by enzyme-linked immunoabsorbent assay, developed in 17 of 23 patients. Neutralizing activity (titer 10(2] was found in only 1 of 23 patients. No immune-mediated sequelae (symptomatic or renal) were identified. Further Phase I and II trials with this molecule will determine whether it will prove to have a better therapeutic index or different spectrum of therapeutic activity from alpha-interferon or gamma-interferon.
Integrated waveguide-coupled terahertz microcavity resonators (2007)

We demonstrate integrated square terahertz microcavity resonators side coupled to waveguides. We present the microcavity transmission spectra for different resonator sizes and coupling strengths. The measured quality factors due to external coupling and cavity loss are found to be between 40 and 90 and between 30 and 40, respectively, for cavity resonance frequencies between 1.077 and 1.331THz.
Regulatory switch enforced by basic helix-loop-helix and ACT-domain mediated dimerizations of the maize transcription factor R (2012)

The maize R2R3-MYB regulator C1 cooperates with the basic helix-loop-helix (bHLH) factor R to activate the expression of anthocyanin biosynthetic genes coordinately. As is the case for other bHLH factors, R harbors several protein-protein interaction domains. Here we show that not the classical but rather a briefly extended R bHLH region forms homodimers that bind canonical G-box DNA motifs. This bHLH DNA-binding activity is abolished if the C-terminal ACT (aspartokinase, chorismate, and TyrA) domain is licensed to homodimerize. Then the bHLH remains in the monomeric form, allowing it to interact with R-interacting factor 1 (RIF1). In this configuration, the R-RIF1 complex is recruited to the promoters of a subset of anthocyanin biosynthetic genes, such as A1, through the interaction with its MYB partner C1. If, however, the ACT domain remains monomeric, the bHLH region dimerizes and binds to G-boxes present in several anthocyanin genes, such as Bz1. Our results provide a mechanism by which a dimerization domain in a bHLH factor behaves as a switch that permits distinct configurations of a regulatory complex to be tethered to different promoters. Such a combinatorial gene regulatory framework provides one mechanism by which genes lacking obviously conserved cis-regulatory elements are regulated coordinately.
Immune tolerance and protection against allergic sensitization (1995)

Recent studies in our laboratory have focused on the nature of the primary T-cell response to inhaled allergens in the regional lymph nodes (RLN) draining the upper airways, in immunologically naive mice and rats. In general terms, the first detectable response involves activation of allergen-specific interleukin 4 (IL-4) secreting CD4+ Th-0/Th-2 cells, which triggers (at least in genetically high-immunoglobulin E (IgE)-responders) an initial burst of IgE antibody synthesis. This is followed by a rapidly expanding interferon gamma (IFN-gamma) response in the RLN, which terminates IL-4 secretion and IgE production. We have presented evidence that the initial source of IFN-gamma in this response is a population of major histocompatibility complex (MHC) class I restricted CD8+ T-cells, which respond specifically to the allergen. The initial activation of these CD8+ T-cells requires a source of exogenous IL-2, which appears to be supplied by the Th-0/Th-2 cells, which are themselves eventually suppressed by the cytokine products of the CD8+ T-cells. It is hypothesized that the IFN-gamma-rich milieu created by the allergen-specific CD8+ T-cells eventually selects for allergen-specific Th-1 cells, which, with chronic stimulation, eventually outgrow the CD8+ population and become dominant in the allergen-specific T-cell memory pool. Our most recent experiments have identified a previously covert but highly potent effector cell subset within the CD8+ T-cell population, in the form of allergen-specific TcR1 (gamma/delta) T-cells. Less than 500 of these cells, purified by positive sorting, are required to regulate the CD4 T-cell response in adult mice or rats, in adoptive transfer experiments.(ABSTRACT TRUNCATED AT 250 WORDS)