gebhart/patrepeval huggingface dataset:
Natriuretic Effect of Equol (1999)

A furosemide-sensitive Na-K-Cl cotransporter (NKCC2 isoform) accounts for almost all luminal NaCl reabsorption in the thick ascending limb of Henle's loop (TALH). The activity of this transport protein is regulated by humoral factors known as cotransport inhibitory factors. One family of these compounds is represented by the urinary phytoestrogens equol and genistein, which inhibit cotransport fluxes at concentrations similar to furosemide. Moreover, they possess salidiuretic potency similar to furosemide in the isolated perfused rat kidney, but are less potent than furosemide (in vivo). Thus, dietary phytoestrogens can be responsible, at least in part, for the low blood pressure of vegetarians.
Effects of four doses of n-3 fatty acids given to hyperlipidemic patients for six months. (1991)

The long-term effects of practical amounts of fish oil on plasma lipids and lipoprotein cholesterol levels, bleeding times, erythrocyte deformabilities, and plasma phospholipid fatty acid (FA) composition were investigated in this trial. Twenty-eight hyperlipidemic patients with elevated cholesterol and triglyceride (TG) levels were randomly assigned to take 3, 6, 9, or 12 capsules of fish oil daily for 6 months, providing 1.25-5 g of n-3 FAs per day. Baseline parameters were compared to values after 1 and 6 months of treatment, and after 1 month of washout. There were no statistically significant changes in total cholesterol levels at any dose. Both low-density-lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C) levels tended to rise, resulting in an unchanged ratio of LDL-C to HDL-C. The TG and very-low-density-lipoprotein cholesterol (VLDL-C) levels decreased significantly with all but the lowest dose. Bleeding times were unaffected despite a nonsignificant 34% increase detected at the highest dose. Red blood cell deformability tended to increase with the two middle doses only. The EPA level in plasma phospholipids was strongly correlated with n-3 FA (FA) consumption. We conclude that long-term treatment of hyperlipidemic patients with practical intakes of n-3 FAs produced persistent reductions in TG levels and no change in the LDL-C/HDL-C ratio.
The Size of Blood–Brain Barrier Opening Induced by Focused Ultrasound is Dictated by the Acoustic Pressure (2014)

Focused ultrasound (FUS) in combination with microbubbles (MBs) has been successfully used in the delivery of various-size therapeutic agents across the blood-brain barrier (BBB). This study revealed that FUS-induced BBB opening size, defined by the size of the largest molecule that can permeate through the BBB, can be controlled by the acoustic pressure as dictated by cavitational mechanisms. Focused ultrasound was applied onto the mouse hippocampus in the presence of systemically administered MBs for trans-BBB delivery of fluorescently labeled dextrans with molecular weights 3 to 2,000 kDa (hydrodynamic diameter: 2.3 to 54.4 nm). The dextran delivery outcomes were evaluated using ex vivo fluorescence imaging. Cavitation detection was employed to monitor the MB cavitation activity associated with the delivery of these agents. It was found that the BBB opening size was smaller than 3 kDa (2.3 nm) at 0.31 MPa, up to 70 kDa (10.2 nm) at 0.51 MPa, and up to 2,000 kDa (54.4 nm) at 0.84 MPa. Relatively smaller opening size (up to 70 kDa) was achieved with stable cavitation only; however, inertial cavitation was associated with relatively larger BBB opening size (above 500 kDa). These findings indicate that the BBB opening size can be controlled by the acoustic pressure and predicted using cavitation detection.
Rapid determination of single base mismatch mutations in DNA hybrids by direct electric field control (1997)

We have demonstrated that controlled electric fields can be used to regulate transport, concentration, hybridization, and denaturation of single- and double-stranded oligonucleotides. Discrimination among oligonucleotide hybrids with widely varying binding strengths may be attained by simple adjustment of the electric field strength. When this approach is used, electric field denaturation control allows single base pair mismatch discrimination to be carried out rapidly (<15 sec) and with high resolution. Electric field denaturation takes place at temperatures well below the melting point of the hybrids, and it may constitute a novel mechanism of DNA denaturation.
Elastase in the Prevention of Arterial Ageing and the Treatment of Atherosclerosis (2007)

Arterial aging is defined as the age-related structural and functional changes in arteries from the precapillary to the aortic level. These include atheromatous changes. Such changes can be estimated in medium-sized or larger arteries by clinical diagnostic studies, including B-mode echography of the carotid artery (thickening of the intima, plaque formation and increase in luminal diameter) and abdominal aorta (plaque formation and increase in luminal diameter). Doppler echography (pulse wave velocity; PWV) and autopsy studies. These changes include distension of the lumen, increased arterial wall thickness (which may be associated with atherosclerotic plaques) and decreased extensibility of the arterial wall. Since 1981, an anti-atherosclerotic drug containing porcine pancreatic elastase 1 (PPE1) has been used for the prevention of arterial aging and the treatment of atherosclerosis in elderly patients in Japan. So far, the age-related increase in PWV has been found to be lower in those who take PPE1 than in controls. The atherosclerotic index of the carotid artery has also been found to be lower in subjects receiving PPE1 treatment than in control subjects. The pharmacological basis of PPE1 therapy, although paradoxical to the consensus opinion of the pathogenic role of elastase in western countries, is discussed with reference to data gathered in Japan. The pathomechanism of arterial aging and atherosclerosis, with special reference to elastin, is reviewed along with the presentation of some of our data.
Melatonin secretion in humans assessed by measuring its metabolite, 6-sulfatoxymelatonin. (1987)

Comparing a direct radioimmunoassay for 6-sulfatoxymelatonin (aMT6s) with an established gas chromatographic/mass spectrometric method for 6-hydroxymelatonin, we found a good correlation r = 0.94 (P less than 0.001, n = 100). aMT6s was stable, both in urine and plasma samples, without preservative, for at least two years at -20 degrees C and for five days at room temperature. Urinary excretion of aMT6s showed considerable inter-individual differences; however, the aMT6s excretion of any one individual was consistent over a four-day period, as assessed by continuous collection from 18 normal volunteers. Total 24-h urinary excretion of aMT6s was significantly correlated with the area under the curve of the respective profiles for plasma melatonin (r = 0.75, P = 0.0002) and plasma aMT6s (r = 0.70, P = 0.0005) for 22 healthy volunteers. At 24:00 h and 03:00 h, sampling plasma at 30-s intervals provided no evidence for episodic secretion (in short pulses) of either melatonin or aMT6s.
Comparative Assessment of a New Breath-Actuated Inhaler in Patients with Reversible Airways Obstruction (1992)

Twenty-five patients with reversible airways obstruction inhaled salbutamol (200 micrograms) from the standard press and breathe-metered dose inhaler or a new breath-actuated metered dose inhaler (Aerolin in the Autohaler inhalation device; 3M Health Care Ltd.) in a single dose, double-blind, double-dummy, 2-period, cross-over study. Forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow rate were measured in the 4-hour period after inhalation. The equivalence of the two inhaler devices was determined by analysis of the peak change and time to peak, with reference to the initial recorded baselines of the measured parameters. The efficacy of the two devices was very similar. The breath-actuated device is likely to benefit inhaler users who suffer from poor co-ordination of actuation and inhalation with a standard inhaler.
Chalcone Derivatives Antagonize Interactions between the Human Oncoprotein MDM2 and p53 (2000)

The oncoprotein MDM2 inhibits the tumor suppressor protein p53 by binding to the p53 transactivation domain. The p53 gene is inactivated in many human tumors either by mutations or by binding to oncogenic proteins. In some tumors, such as soft tissue sarcomas, overexpression of MDM2 inactivates an otherwise intact p53, disabling the genome integrity checkpoint and allowing cell cycle progression of defective cells. Disruption of the MDM2/p53 interaction leads to increased p53 levels and restored p53 transcriptional activity, indicating restoration of the genome integrity check and therapeutic potential for MDM2/p53 binding antagonists. Here, we show by multidimensional NMR spectroscopy that chalcones (1,3-diphenyl-2-propen-1-ones) are MDM2 inhibitors that bind to a subsite of the p53 binding cleft of human MDM2. Biochemical experiments showed that these compounds can disrupt the MDM2/p53 protein complex, releasing p53 from both the p53/MDM2 and DNA-bound p53/MDM2 complexes. These results thus offer a starting basis for structure-based drug design of cancer therapeutics.
<title>Electrically switchable Bragg grating technology for projection displays</title> (2001)

DigiLens Inc. (Sunnyvale, California) has developed the Application Specific Optical Element (ASOE) based on Electrically Switchable Bragg Gratings (ESBGs) using an advanced Holographic Polymer Dispersed Liquid Crystal material system. One of the embodiments of this fundamental technology is a customizable white light color sequential filter system which aims to replace traditional color wheel assemblies in microdisplay-based display applications such as business projectors, HDTV and large computer monitors. ASOEs are essentially stacks or laminates of intrinsically thin ESBGs encapsulated using transparent substrates. ASOEs have no moving parts; they are completely solid state and silent in operation. They offer the benefits of holographic optical elements in terms of being able to compress conventional optical systems into compact and lightweight form factors. Their switching speed is fast enough for color sequential display applications. They will have a major impact on the complexity and cost of a broad gamut of microdisplay applications, including projection and near- eye. This paper reviews the role of reflective ASOE filters in projection systems, with reference to design concepts currently in development.
Microfluidic device reads up to four consecutive base pairs in DNA sequencing-by-synthesis (2004)

We have developed the first fully integrated microfluidic system for DNA sequencing-by-synthesis. Using this chip and fluorescence detection, we have reliably sequenced up to 4 consecutive bps. The described sequencer can be integrated with other microfluidic components on the same chip to produce true lab-on-a-chip technology. The surface chemistry that was designed to anchor the DNA to elastomeric microchannels is useful in a broad range of studies and applications.
Effect of syk inhibition by TAK659 on proliferative, survival, and migratory signals from the microenvironment in chronic lymphocytic leukemia. (2014)

7058 Background: Chronic lymphocytic leukemia (CLL) is characterized by the accumulation and proliferation of monoclonal CD5+ mature B-cells in peripheral blood, lymph nodes (LN), and bone marrow (BM). The microenvironment in BM and LN induces proliferation of CLL cells and protects them from spontaneous and chemotherapy-induced apoptosis. Syk is a tyrosine kinase essential for the BCR signaling pathway that also participates in signaling from chemokine receptors and has been shown to be deregulated in CLL. Therefore Syk has been hypothesized to be a rational candidate for targeted therapy in CLL and its inhibition has been tested with the non-specific Syk inhibitor fostamatinib (R406). Against this background we tested the effectiveness of the highly specific Syk inhibitor TAK-659 in suppressing the induction of survival, proliferation and migration of CLL cells by the microenvironment. Methods: To mimic the microenvironment of the proliferative centers ex vivo, we co-cultured primary CLL cells with BM stromal cells (BMSC), CD40L, and CpG ODN along with anti-IgM (BCR stimulation). We evaluated the effects of TAK-659 on BCR signaling, proliferation, apoptosis and chemotaxis. Results: The co-culture system with BMSC and different stimuli induced survival and proliferation of primary CLL cells. Moreover, in this system CLL cells became chemoresistant to fludarabine and bendamustine. TAK-659 inhibited the phosphorylation of Syk, Akt, and ERK1/2 after BCR stimulation. TAK-659 induced apoptosis of co-cultured CLL cells at lower doses than R406. In addition, combination of TAK659 and fludarabine showed a synergistic effect in inducing apoptosis. TAK-659 also inhibited co-culture-induced proliferation, as assessed by Ki-67 expression, and significantly decreased chemotaxis of CLL cells toward CXCL12, CXCL13 and BMSCs. Conclusions: These findings demonstrate that, in this ex-vivo system, the specific inhibition of Syk by TAK-659 effectively overcomes the microenvironment signals that promote proliferation, survival and chemoresistance of primary CLL cells. Altogether, this study provides a rationale for the clinical development of TAK-659 in CLL.
Comparison of a New Quantitative ompA -Based Real-Time PCR TaqMan Assay for Detection of Chlamydia pneumoniae DNA in Respiratory Specimens with Four Conventional PCR Assays (2003)

Chlamydia pneumoniae, an important respiratory pathogen, is difficult to culture, and detection rates by conventional PCRs vary considerably. A new quantitative ompA-based real-time PCR assay based on TaqMan technology for detection of C. pneumoniae in respiratory samples is described, and its performance in terms of sensitivity and reproducibility is compared with those of four published conventional PCRs (one single-step PCR targeting a cloned PstI fragment; two nested PCRs, one targeting the 16S rRNA gene followed by hybridization and the other targeting the ompA gene; and a touchdown enzyme time-release [TETR] PCR also targeting the 16S rRNA gene). Both ompA-based PCRs showed the best analytical sensitivity. All five assays could detect even lower target levels from spiked sputum, with the 16S rRNA assays performing better than the ompA-based nested PCR (10(-6) inclusion-forming units [IFU] were detected in four of four and two of four replicates by the 16S rRNA TETR PCR and the 16S rRNA nested PCR, respectively). In general, the ompA-based real-time protocol produced the most consistent positive results for all replicates tested down to 10(-6) IFU. Eight of 45 patient sputum specimens (18%) were C. pneumoniae DNA positive in at least one of four replicates tested by at least one assay. Without taking into consideration the analytical sensitivity or the reproducibility of the test results, the numbers of C. pneumoniae DNA-positive sputum specimens (n = 8) were four, three, two, two, and one for the 16S rRNA TETR assay, the PstI-based single-step PCR, the ompA-based real-time PCR, the ompA-based nested touchdown PCR, and the 16S rRNA-based nested PCR, respectively. However, the overall rate of concordance of positive results was low. Only one cell culture-positive sputum specimen was positive by four of five assays (14 of 16 replicates; mean cycle threshold value, 25; 10(8) particles/ml of sputum). Thirty-seven specimens were C. pneumoniae negative by all five assays for all replicates tested, as were all negative controls (n = 65 to 100 per testing panel). No PCR inhibitors were detected by real-time PCR or by the 16S rRNA-based nested assay. We confirm that the analytical sensitivity of an assay for the detection of C. pneumoniae does not necessarily predict its ability to detect its target in sputum. A quantitative, fast, and easy-to-handle diagnostic approach such as the ompA-based real-time TaqMan PCR described here might improve the detection of C. pneumoniae in respiratory samples.
Circumventing tolerance to generate autologous monoclonal antibodies to the prion protein. (1996)

Prion diseases are disorders of protein conformation and do not provoke an immune response. Raising antibodies to the prion protein (PrP) has been difficult due to conservation of the PrP sequence and to inhibitory activity of alpha-PrP antibodies toward lymphocytes. To circumvent these problems, we immunized mice in which the PrP gene was ablated (Prnp 0/0) and retrieved specific monoclonal antibodies (mAbs) through phage display libraries. This approach yielded alpha-PrP mAbs that recognize mouse PrP. Studies with these mAbs suggest that cellular PrP adopts an unusually open structure consistent with the conformational plasticity of this protein.
New insights into the pharmacological and toxicological effects of thalidomide. (2003)

The molecular activity of thalidomide comprises a wide range of mechanisms. Alteration of cytokine synthesis and release may be as important as changes in lymphocyte trafficking and leukocyte migration. Since endothelial cells play an important role in leukocyte extravasation and maintenance of inflammatory processes in the affected tissue, thalidomide-induced alterations of cellular adhesion molecules, and consequently changes of interaction of leukocytes with the endothelial cell layer, will result in modulation of the response in inflammation and immunity. Thalidomide mainly reduces tumor necrosis factor (TNF)-alpha production by macrophages, and its TNF alpha antagonist properties explain the beneficial effects in several TNF alpha-associated complications of severe diseases. Pathophysiologically relevant alterations most likely include gene regulatory effects, with interference in growth factor-dependent pathways known to be involved in teratogenesis, and effects on the transcriptional control of the inflammatory response via nuclear factor (NF)-kappa B. The effects of thalidomide, its enantiomers and analogs, on a broad range of diseases, and their differential pharmacokinetic and pharmacodynamic properties, give the scope for ongoing investigations in the search for analogs with better selectivity but without thalidomide-related side effects and teratogenicity.
Design techniques for monolithic operational amplifiers (1969)

The characteristics of recently developed integrated-circuit components are reviewed and some new devices are described. Their impact on the design of monolithic operational amplifiers is also discussed. Emphasis is placed on realizing particularly good dc characteristics-especially low input current. However, techniques for obtaining higher operating speeds are also covered.
QoS aware storage cache management in multi-server environments (2011)

In this paper, we propose a novel two-step approach to the management of the storage caches to provide predictable performance in multi-server storage architectures: (1) An adaptive QoS decomposition and optimization step uses max-flow algorithm to determine the best decomposition of application-level QoS to sub-QoSs such that the application performance is optimized, and (2) A storage cache allocation step uses feedback control theory to allocate shared storage cache space such that the specified QoSs are satisfied throughout the execution.
NUTRIENTES NA BIOMASSA, RENDIMENTO E QUALIDADE DE ABACAXI NA SEGUNDA COLHEITA, EM FUNÇÃO DO PREPARO DO SOLO E TÉCNICAS DE PLANTIO (2000)

Buscando subsídios para melhor manejar o solo e a adubação para o abacaxizeiro, avaliou-se o efeito de técnicas de preparo do solo (convencional, cultivo em faixas e plantio direto) e de plantio (sulco e chuço) sobre o rendimento de biomassa, concentração e quantidade de nutrientes nela contidos, produtividade e qualidade de frutos do abacaxizeiro cv. Pérola na segunda colheita. O ensaio foi conduzido a campo entre ago./97 e jan./2000 na E E de Maquiné-RS, em Chernossolo Háplico Órtico típico. As técnicas de plantio não influenciaram as variáveis analisadas. As técnicas de preparo de solo não afetaram a produção de biomassa e a concentração de nutrientes na folha. No preparo convencional a produtividade de biomassa verde e seca e de frutos foi de 45,6, 7,4 e 14,4 t/ha e as quantidades de N, P, K, Ca e Mg nela contida foram: 99, 10, 238, 10 e 10 kg/ha, respectivamente. Mantidas as proporções de biomassa produzida e os nutrientes nela contidos, no nível tecnológico alto MODEL, 1999 no primeiro ciclo, o abacaxizeiro demandaria aproximadamente 587 kg de N e 946 kg de K O. A produtividade e a porcentagem de colheita no preparo convencional (14,35 t/ha e 51,2%) foram maiores do que no plantio direto (8,61 t/ha e 31,2 %), respectivamente. O diâmetro e o comprimento da coroa dos frutos, no preparo convencional, foram maiores do que no plantio direto, mas o comprimento dos frutos e o teor de sólidos solúveis totais, não foram afetados pelos tratamentos.
Integrated continuous production of recombinant therapeutic proteins (2012)

In the current environment of diverse product pipelines, rapidly fluctuating market demands and growing competition from biosimilars, biotechnology companies are increasingly driven to develop innovative solutions for highly flexible and cost-effective manufacturing. To address these challenging demands, integrated continuous processing, comprised of high-density perfusion cell culture and a directly coupled continuous capture step, can be used as a universal biomanufacturing platform. This study reports the first successful demonstration of the integration of a perfusion bioreactor and a four-column periodic counter-current chromatography (PCC) system for the continuous capture of candidate protein therapeutics. Two examples are presented: (1) a monoclonal antibody (model of a stable protein) and (2) a recombinant human enzyme (model of a highly complex, less stable protein). In both cases, high-density perfusion CHO cell cultures were operated at a quasi-steady state of 50-60 × 10(6) cells/mL for more than 60 days, achieving volumetric productivities much higher than current perfusion or fed-batch processes. The directly integrated and automated PCC system ran uninterrupted for 30 days without indications of time-based performance decline. The product quality observed for the continuous capture process was comparable to that for a batch-column operation. Furthermore, the integration of perfusion cell culture and PCC led to a dramatic decrease in the equipment footprint and elimination of several non-value-added unit operations, such as clarification and intermediate hold steps. These findings demonstrate the potential of integrated continuous bioprocessing as a universal platform for the manufacture of various kinds of therapeutic proteins.
Synthesis of 1-alkoxy-3,3-dialkyltriazene 2-oxides from alkoxyamines and nitrosoamines (1987)

The oxidation of O-alkylhydroxylamines by lead tetraacetate in the presence of dialkynitrosoamines leads to the 1-alkoxy-3,3-dialkyltriazene 2-oxides in yields up to 50%. The products were isolated by distillation. The chromato-mass spectrometric analysis of the reaction mixtures and compounds synthesized was carried out on an LKB-2091 spectrometer. The ionizing electron energy was 70 and 12 eV.