gebhart/patrepeval huggingface dataset:
Role of the sympathetic nervous system in human hypertension (1998)

Animal studies have shown conclusively that sympathetic neural factors are involved in the development and/or maintenance of high blood pressure. Whether this is also the case for human hypertension has been documented less conclusively, owing to technical difficulties in assessing human adrenergic function. Recent studies have used sophisticated and sensitive techniques to evaluate sympathetic activity in humans, e.g. the norepinephrine spillover method and the microneurographic quantification of sympathetic nerve traffic, allowing documentation of the participation of adrenergic mechanisms in the early and late phases of the hypertensive process. Evidence has been also provided that the activation of the sympathetic nervous system (1) is peculiar to the essential hypertensive state, (2) parallels the degree of the blood pressure elevation, (3) is triggered by reflex and humoral mechanisms and (4) may exert deleterious metabolic and cardiovascular effects, accelerating the progression of the end organ damage accompanying hypertension. These findings explain why non-pharmacological and pharmacological approaches to the treatment of hypertension should be aimed not only at lowering elevated blood pressure values but also at exerting sympathoinhibitory effects.
A high-speed ESFI SOS programmable logic array with an MNOS version (1975)

A programmable logic array (PLA) with J-K flip-flops as feedback loops and having a maximum operating speed of 12 MHz has been designed and realized in epitaxial-silicon-films-on-insulators (ESFI) silicon-on-sapphire (SOS) technology. The advantages of the ESFI SOS technology and the circuit of the PLA are described and experimental results are presented. In addition, a twin PLA using metal-nitride-oxide-semiconductor (MNOS) transistors in the AND and OR matrices and having the same number of inputs, outputs, and feedback loops as the mask-programmable PLA has been designed. This MNOS PLA has full on-chip decoding capability and can be programmed or reprogrammed individually. The circuit of the MNOS PLA is described and the speed of the device is calculated.
One-Pot Synthesis of Anionic (Nitrogen) and Cationic (Sulfur) Codoped High-Temperature Stable, Visible Light Active, Anatase Photocatalysts (2009)

An efficient and straightforward method for the preparation of nitrogen and sulfur (N, S) codoped high-temperature stable, visible light active, anatase titania is reported. For the first time simultaneous nitrogen and sulfur doping was achieved using a single source, ammonium sulfate [(NH4)2SO4], as the modification agent of the titanium isopropoxide (TTIP) precursor. A stoichiometric modification of 1:8 TTIP:(NH4)2SO4 composition (TNS8) was found to be the most effective in extending the stability of anatase to higher temperatures. This particular modification resulted in 100% anatase at 850 °C and 41% anatase at 900 °C, whereas the control titania contained only 12% anatase at 700 °C and completely transformed to rutile at 800 °C. Codoped (N, S) titania was investigated by a range of characterization techniques including XRD, Raman spectroscopy, XPS, and FTIR. XPS indicated the existence of nitrogen as an anion dopant and sulfur as a cation dopant within the TiO2 lattice. The UV/visible and visible light photocatalytic studies were carried out using the rhodamine 6G dye as a model system. The visible light photocatalytic activity of the TNS8 sample calcined at 850 °C was double that of Degussa P25, and the rate constant calculated by pseudo-first-order kinetics was 0.019 min−1 for the TNS8 sample and 0.008 min−1 for Degussa P25. This higher photocatalytic activity was attributable to a combination of improved anatase phase stability, higher surface area, and codoped (N, S) titania lattice. Moreover, this codoped (N, S) sample also exhibits excellent photocatalytic activity under UV/visible light.
Predominant role of alpha 4-integrins for distinct steps of lymphoma metastasis. (1996)

To analyze the role of alpha4-integrins in lymphoma metastasis, sublines of the T-cell lymphoma LB were generated by retrovirus-mediated gene transfer that differ exclusively in the expression of alpha4-integrins. Using LB-alpha4 and control LB-NTK cells, we demonstrate that expression of alpha4-integrins strongly suppresses metastasis formation of LB lymphoma cells in secondary lymphoid organs such as spleen, mesenteric and peripheral lymph nodes, or Peyer's patches after i.v. injection into syngeneic BALB/c mice. Moreover, alpha4-integrin expression inhibited development of metastatic tumors in liver, lung, and kidney. Expansion of LB lymphoma cells in bone marrow was not affected by alpha4-integrin expression. In vivo migration assays using 51Cr-labeled lymphoma cells demonstrated that low-metastatic LB-alpha4 cells accumulated with the same efficiency as high-metastatic LB-NTK cells in all target organs examined and were even enriched in mucosal lymphoid organs. Collectively, these results indicate that alpha4-integrins inhibit metastasis formation of lymphoma cells at a stage subsequent to the invasion of target organs.
Generation and monitoring of cell lines producing humanized antibodies. (1999)

Antibody humanization has eliminated or reduced the human antimouse antibody response associated with the administration of murine antibodies. We have successfully humanized three different antibodies: (a) hMN-3 (granulocyte targeting); (b) hMu-9 (colorectal cancer targeting); and (c) hWI2 (anti-idiotype to the anti-carcinoembryonic antigen antibody MN-14). All humanized antibodies demonstrated immunoreactivities comparable to their parent counterparts. Previously, we reported the generation of high productivity cell lines for hMN-14 and hLL2 using the amplifiable vector pdHL2. Through amplification, selection, and cloning procedures, cell lines capable of large scale production were established, and further enhancement of production was achieved by a fed-perfusion bioreactor process. Using a similar and improved approach, we have enhanced the production of the above-mentioned humanized antibodies by gene amplification induced by a stepwise increase in the concentration of methotrexate in the culture media. A reliable IgG determination method is essential to monitor amplification, especially at the final cloning stage, for the selection of the subclones with the highest productivity. We found that measurement of humanized IgG concentration in culture media supplemented with more than 1 microM methotrexate by a standard ELISA assay could be unreliable and misleading. Whereas the determination of antibody by adsorption/elution on protein A from a 100-ml culture is accurate and reproducible, the method is time-consuming, tedious, and labor intensive. We have recently developed a Western blot assay that enables us to monitor the productivity of the cultures. The assay is simple and sensitive, and it makes simultaneous determinations of relative antibody production from individual clones at the 96-well stage feasible. With this method, amplification, cloning, and adaptation to serum-free conditions of multiple cell lines can be monitored in an efficient manner.
A microfluidic approach for in vitro assessment of interorgan interactions in drug metabolism using intestinal and liver slices (2010)

Over the past two decades, it has become increasingly clear that the intestine, in addition to the liver, plays an important role in the metabolism of xenobiotics. Previously, we developed a microfluidic-based in vitro system for the perifusion of precision-cut liver slices for metabolism studies. In the present study, the applicability of this system for the perifusion of precision-cut intestinal slices, and for the sequential perifusion of intestinal and liver slices, all from rat, was tested to mimic the in vivo first pass situation. Intestinal and liver slices, exposed to the substrates 7-ethoxycoumarin (7-EC), 7-hydroxycoumarin (7-HC) and lidocaine (Li), exhibited similar metabolic rates in the biochip and in the well plates for periods of at least 3 h. The metabolic rate remained the same when two slices were placed in adjacent microchambers and perifused sequentially. In addition, the system has been adapted to sequentially perifuse intestinal and liver tissue slices in a two-compartment co-culture perfusion system with a continuous flow of medium. It becomes possible to direct metabolites or other excreted compounds formed by an intestinal slice in the first compartment to the second compartment containing a liver slice. The intestine does not influence liver metabolism for these substrates. The interplay between these two organs was demonstrated by exposing the slices to the primary bile acid, chenodeoxycholic acid (CDCA). CDCA induced the expression of fibroblast growth factor 15 (FGF15) in the intestinal slice, which resulted in a stronger down-regulation of the enzyme, cytochrome P450 7A1 (CYP7A1), in the liver slice in the second compartment than when the liver slice was exposed to CDCA in a single-microchamber biochip. We thus demonstrate in this paper that intestinal slices, in addition to liver slices, remain functional in the biochip under flow conditions, and that the two-microchamber biochip has great potential for the study of interorgan effects. This is the first example of the incorporation of both liver and intestinal slices in a microfluidic device. Use of this microfluidic system will improve our insight into interorgan interactions and elucidate as yet unknown mechanisms involved in toxicity, gene regulation and drug-drug interactions.
Comparative effects of various classes of mouse interferons on macrophage activation for tumor cell killing. (1985)

The effects of mouse interferon-alpha (MuIFN-alpha), -beta (MuIFN-beta), and -gamma (MuIFN-gamma) on macrophage activation for tumor cell killing were determined by using proteose peptone-elicited peritoneal macrophages from C3H/HeN and C3H/HeJ mice under conditions that either included or were free of detectable endotoxin. Alone, under the conditions used, none of the interferons was able to activate macrophages directly for tumor cell killing. However, with a second signal provided to responsive macrophages by contaminating endotoxin, added bacterial lipopolysaccharide (LPS), or heat-killed Listeria monocytogenes (HKLM), all three types of interferon induced cytolytic activity, with MuIFN-gamma approximately 500 to 1000-fold more active than either MuIFN-alpha or -beta. Thus, all three interferons were able to prime macrophages for killing but required a second signal before cytolytic activity could be expressed. When MuIFN-gamma was mixed with either MuIFN-alpha or -beta and placed on macrophages, little or no killing developed. Mixtures of MuIFN-gamma with either MuIFN-alpha or -beta did increase the sensitivity of macrophages to triggering by LPS, however, compared with macrophages treated with MuIFN-gamma alone. The results are collectively important because they i) confirm that significant quantitative differences exist between the various interferons with regard to their capacity to prime macrophages for tumor cell killing; ii) indicate that to be an efficient activator each type of interferon must be combined with a second stimulus, such as LPS or HKLM; iii) show that neither MuIFN-alpha nor -beta can provide an efficient second triggering signal for macrophages that are primed by MuIFN-gamma; and iv) document that mixtures of MuIFN-gamma with either MuIFN-alpha or -beta are most efficient at inducing priming, compared with any one of the interferons used alone.
IMPROVEMENT OF CARDIAC OUTPUT AND LIVER BLOOD FLOW AND REDUCTION OF PULMONARY VASCULAR RESISTANCE BY INTRAVENOUS INFUSION OF l-ARGININE DURING THE EARLY REPERFUSION PERIOD IN PIG LIVER TRANSPLANTATION1 (1997)

From these data, we conclude that the infusion of L-arginine during OLT improves the hemodynamic performance of the heart, lung, and liver.
Pyridone Methylsulfone Hydroxamate LpxC Inhibitors for the Treatment of Serious Gram-Negative Infections (2012)

The synthesis and biological activity of a new series of LpxC inhibitors represented by pyridone methylsulfone hydroxamate 2a is presented. Members of this series have improved solubility and free fraction when compared to compounds in the previously described biphenyl methylsulfone hydroxamate series, and they maintain superior Gram-negative antibacterial activity to comparator agents.
Small form factor full parallax tiled light field display (2015)

With the recent introduction of Ostendo’s Quantum Photonic Imager (QPI) display technology, a very small pixel pitch, emissive display with high brightness and low power consumption became available. We used QPI’s to create a high performance light field display tiles with a very small form factor. Using 8 of these QPI light field displays tiled in a 4x2 array we created a tiled full parallax light field display. Each individual light field display tile combines custom designed micro lens array layers with monochrome green QPIs. Each of the light field display tiles can address 1000 x 800 pixels placed under an array of 20 x 16 lenslets with 500 &mu;m diameters. The light field display tiles are placed with small gaps to create a tiled display of approximately 46 mm (W) x 17 mm (H) x 2 mm (D) in mechanical dimensions. The prototype tiled full parallax light field display demonstrates small form factor, high resolution and focus cues.
Superior Neutralizing Antibody Response and Protection in Mice Vaccinated with Heterologous DNA Prime and Virus Like Particle Boost against HPAI H5N1 Virus (2011)

These results provide strong support for clinical evaluation of heterologous DNA-VLP prime-boost strategy as a public health intervention against a possible H5N1 pandemic.
Wavelength-Selective Reflector Based on a Circular Array of Coupled Microring Resonators (2004)

We propose and analyze a novel type of wavelength-selective reflector for planar lightwave technology based on a circular array of coupled microring resonators. Narrow-band reflection peaks can be achieved without the need for additional complex lithography and processing steps. The ring resonators also allow for simple and wide-range tuning of the reflection peak.
A Comparison of Azacitidine and Decitabine Activities in Acute Myeloid Leukemia Cell Lines (2010)

These data demonstrate shared mechanisms of action of AZA and DAC on DNA-mediated markers of activity, but distinctly different effects in their actions on cell viability, protein synthesis, cell cycle, and gene expression. The differential effects of AZA may be mediated by RNA incorporation, as the distribution of AZA in nucleic acid of KG-1a cells was 65:35, RNA:DNA.
Effect of endotoxin in IL-1 β-deficient mice (1996)

IL-1 plays an important role in the pathophysiologic responses to infection and inflammation, in part by mediating its own production and that of other proinflammatory cytokines. However, the relative contribution of IL-1 alpha and IL-1 beta to the inflammatory response has not been well clarified. Using IL-1 beta-deficient (IL-1 beta -/-) mice, we investigated the specific role of IL-1 beta in the in vivo and in vitro response to LPS. No differences between IL-1 beta +/+ and IL-1 beta -/- mice were observed in circulating levels for IL-1 alpha, IL-6, or TNF-alpha after the systemic administration of either a low (5 micrograms/kg) or high (5 mg/kg) dose of LPS. IL-1 beta -/- mice also had a normal response to LPS in terms of activation of the hypothalamus-pituitary-adrenal axis, hypoglycemia, serum amyloid A production, and anorexia. IL-1 beta -/- mice were normally sensitive to the lethal effect of LPS and were protected against LPS toxicity when pretreated with low-dose LPS. However, in vitro, peritoneal macrophages from IL-1 beta -/- mice stimulated with LPS produced significantly less IL-1 alpha than macrophages from IL-1 beta +/+ mice (p < 0.05). No differences in IL-6 or TNF-alpha synthesis were observed between macrophages from IL-1 beta +/+ and IL-1 beta -/- mice. In summary, our results suggest that either IL-1 beta is not essential for the in vivo systemic response to LPS or that its role can be fulfilled by other cytokines with overlapping activities.
Identification of putative multifunctional peptide synthetase genes using highly conserved oligonucleotide sequences derived from known synthetases (1992)

Many peptide antibiotics in prokaryotes and lower eukaryotes are produced non-ribosomally by multi-enzyme complexes. Analysis of gene-derived amino acid sequences of some peptide synthetases of bacterial and fungal origins revealed a high degree of conservation (35–50% identity). The genes encoding those peptide synthetases are clustered into large operons with repetitive domains (about 600 amino acids), in the case of synthetases activating more than one amino acid. We used two 35-mer oligonucleotides derived from two highly conserved regions of known peptide synthetases to identify the surfactin synthetase operon in Bacillus subtilis ATCC 21332, a strain not accessible to genetic manipulation. We show that the derived oligonucleotides can be used not only for the identification of unknown peptide synthetase genes by hybridization experiments but also in sequencing reactions as primers to identify internal domain sequences. Using this method, a 25.8-kb chromosomal DNA fragment bearing a part of the surfactin biosynthesis operon was cloned and partial sequences of two internal domains were obtained.
Cystathionine beta-synthase null homocystinuric mice fail to exhibit altered hemostasis or lowering of plasma homocysteine in response to betaine treatment (2010)

Cystathionine beta-synthase (CBS) deficient homocystinuria is an inherited metabolic defect that if untreated typically results in mental retardation, thromboembolism and a range of connective tissue disturbances. A knockout mouse model has previously been used to investigate pathogenic mechanisms in classical homocystinuria (Watanabe et al., PNAS 92 (1995) 1585-1589). This mouse model exhibits a semi-lethal phenotype and the majority of mice do not survive the early neonatal period. We report here that the birth incidence of cbs (-/-) mice produced from heterozygous crosses is non-Mendelian and not significantly improved by treatment with either the Hcy lowering compound betaine or the cysteine donor N-acetylcysteine. Betaine treatment did improve survival of cbs (-/-) mice and restored fertility to female cbs (-/-) mice but did so without significantly lowering Hcy levels. Surviving cbs (-/-) mice failed to show any alteration in coagulation parameters compared to wild-type controls. Moribund cbs (-/-) mice exhibited severe liver injury and hepatic fibrosis while surviving cbs (-/-) mice although less severely affected, still exhibited a level of severe liver injury that is not found in the human disease. The hepatopathy observed in this model may offer an explanation for the failure of cbs (-/-) mice to respond to betaine or exhibit a hypercoagulative phenotype. We conclude that although this model provides useful data on the biochemical sequelae of classical homocystinuria, it does not successfully recapitulate a number of important features of the human disease and its use for studying mechanisms in homocystinuria should be treated with caution as the hepatopathy produces changes which could influence the results.
A new immuno quantitative method by latex agglutination--application for the determination of serum C-reactive protein (CRP) and its clinical significance. (1986)

We developed a new method for the determination of CRP by latex immunoassay which measures the increase in optical density as a result of latex agglutination due to antigen-antibody reaction. This latex agglutination photometric immunoassay can be used for quantitative analysis of various biological substances. We have established the best conditions for CRP determination for the instrument employed here (LA system) which allows rapid and accurate to low concentration measurement. The measurement range of the system is from 0.01-3 mg/l (non-diluted method), which when compared to the lower detection limit of RIA, 3 micrograms/l, it has the same order of magnitude. It is more sensitive than radial immunodiffusion which has the lower detection limit of 2 mg/l and has the similar value to that of radio-electroimmunodiffusion, 10 micrograms/l. Furthermore, the usual method used in the clinical laboratories, the capillary microprecipitation method, has the lower detection limit of approximately 10 mg/l. The method presented here is adequately sensitive to measure the low concentration of CRP among healthy individuals which has not been possible except by using RIA. The normal value derived from 106 healthy individuals by this method is found to be 0.2 +/- 0.2 mg/l (mean +/- 2SD).
Benzocycloarene hydroxylation by P450 biocatalysis (2002)

Experimental and theoretical studies of the hydroxylation of a family of benzocycloarene compounds [benzocyclobutene, benzocyclopentene (indan), benzocyclohexene (tetralin), and benzocycloheptene] by wild type and Y96F mutant P450cam were performed in order to understand the factors affecting product distribution, catalytic rate and cofactor utilization. The products of all reactions except that of benzocycloheptene were regiospecifically hydroxylated in the 1-position. Reaction energetics predominated over active site steric constraints in this case so that quantum mechanical calculations (B3LYP/6-31G*) comparing the energetics of all possible radical intermediates successfully predicted hydroxylation at the 1- and 3-positions of benzocycloheptene, and at the 1-position for the other three compounds. However, the fact that the ratio of 1-alcohol to 3-alcohol changes significantly between wild type and Y96F mutant P450cam indicates that active site geometry and composition also play a significant role in determining BCA7 product regiospecificity. The indan and tetralin reaction products were stereoselective for the R enantiomer (88 and 94%, respectively). Steric constraints of the active site were confirmed by molecular dynamics calculations (locally enhanced sampling dynamics) to control enantiomer distribution for tetralin hydroxylation. NADH coupling, binding affinity, and product turnover rates were dramatically higher for Y96F P450cam, showing that the removal of the active site hydroxyl group on tyrosine makes the enzyme better suited for oxidation of these hydrophobic compounds. NADH coupling, binding affinity and product turnover rate for each enzyme generally increased with arene ring size. For both enzymes, NADH coupling and product turnover rates were correlated with the extent of high-spin shift upon substrate binding as determined by the shift in Soret absorption bands at 417 and 391 nm.
Left Ventricular Volume Reduction Surgery: The 4th International Registry Report 2004 (2005)

Avoidance of risk factors appears to have contributed to the recent survival improvement and may help stratify patients for LVVR. While performance has been decreasing, the concept has been extended to other LVVR and less invasive procedures, which are now under clinical trials.
Implementation of local area digital audio broadcasting system upon 12C network (2004)

Conventionally, local area audio broadcasting systems use analog channels for voice transmission. They are constructed with one main voice transmitter and many loudspeakers. The inherent disadvantages lie in the difficulties to make individual or restricted area communication without additional complex switching box; besides, a pre-planed wiring are necessary, which makes any on-line re-distribution almost impossible. To overcome above problems, the system developed here uses digital voice transmission upon I2C network. This system has many advantages: enhance the voice quality of broadcasting, encrypts the voice data for secret communication and reduce the overall system cost for construction and maintenance. Other devices such as sensors and actuators can be added or removed from this I2C bus easily; therefore a cost effective network of communication with security/monitoring functions for buildings, plants or communities can be built.