gebhart/patrepeval huggingface dataset:
Phenotypic Fingerprinting of Small Molecule Cell Cycle Kinase Inhibitors for Drug Discovery (2009)

Phenotypic drug discovery, primarily abandoned in the 1980's in favor of targeted approaches to drug development, is once again demonstrating its value when used in conjunction with new technologies. Phenotypic discovery has been brought back to the fore mainly due to recent advances in the field of high content imaging (HCI). HCI elucidates cellular responses using a combination of immunofluorescent assays and computer analysis which increase both the sensitivity and throughput of phenotypic assays. Although HCI data characterize cellular responses in individual cells, these data are usually analyzed as an aggregate of the treated population and are unable to discern differentially responsive subpopulations. A collection of 44 kinase inhibitors affecting cell cycle and apoptosis were characterized with a number of univariate, bivariate, and multivariate subpopulation analyses demonstrating that each level of complexity adds additional information about the treated populations and often distinguishes between compounds with seemingly similar mechanisms of action. Finally, these subpopulation data were used to characterize compounds as they relate in chemical space.
HMM-based databases in InterPro (2002)

Protein family databases are an important resource for protein annotation and understanding protein evolution and function. In recent years hidden Markov models (HMMs) have become one of the key technologies used for detection of members of these families. This paper reviews the Pfam, TIGRFAMs and SMART databases that use the profile-HMMs provided by the HMMER package.
Structure-Related Initiation of Reentry by Rapid Pacing in Monolayers of Cardiac Cells (2006)

This study examines how a zigzag pattern of conduction, a form of structural heterogeneity frequently found in old or diseased hearts, affects the vulnerability to reentry during rapid pacing. A central rectangular island (8x4 mm) containing a predefined zigzag pattern was created in cultured isotropic monolayers of neonatal rat ventricular myocytes. Impulse propagation was optically mapped from 253 sites using voltage-sensitive dye and was anisotropic within the zigzag island. With increasing interval between neighboring transverse connections (a), relative to the distance between longitudinal strands (b), transverse conduction velocity (CV) decreased to 66+/-6%, 20+/-2%, and 15+/-2% of CV in the surrounding isotropic region, whereas longitudinal CV increased to 102+/-8%, 113+/-12%, and 131+/-23% for a:b ratios of 1:1, 1:5, and 1:9, respectively. During rapid pacing, propagation distal to the island was steered from the side of the island with more transverse connections ("dominant" side) toward the side with fewer connections ("weak" side). Increased asymmetry in the pattern accentuated this effect, and resulted in increased rate-dependent differences in CV on the 2 sides. Consequently, a functional obstacle formed on the weak side, followed by development of single loop reentry. The reentrant wave revolved around a line of block defined by the border of the island. Reentry chirality was determined by the weak side location, and the pacing rate needed to initiate reentry decreased with increased asymmetry in the pattern. In conclusion, reentry is readily induced by rapid pacing in confluent cardiac cell monolayers containing a central and asymmetric island of zigzag conduction.
High quality ultra-thin TiO/sub 2//Si/sub 3/N/sub 4/ gate dielectric for giga scale MOS technology (2002)

This paper presents the study of physical and electrical properties of ultra-thin (2.0-3.0 nm EOT) TiO/sub 2//Si/sub 3/N/sub 4/ stack gate dielectrics for future giga scale MOS technology. Both layers of the dielectric stack are deposited by the jet vapor deposition (JVD) process. Our experimental data indicate that the leakage current in the TiO/sub 2//Si/sub 3/N/sub 4/ stack is substantially (several decades) lower than that in single oxide layer of the same equivalent oxide thickness (EOT). These films also exhibit excellent interface quality, dielectric reliability, and MOSFET transistor performance comparable to that of thermal oxide.
Enterotoxins from Clostridium difficile; diarrhoeogenic potency and morphological effects in the rat intestine. (1990)

The action of toxins A, B, and C from Clostridium difficile was studied in the small intestine and colon of rats. All three caused fluid accumulation in the small intestine, maximal secretion being induced by 1 micrograms of toxin A, 20 micrograms of B, and 15 micrograms of C. Both toxins A and C caused shedding of epithelial cells from the villi without visible damage to crypt cells; toxin A caused further extensive necrosis and bleeding. Toxin B caused secretion without visible damage to the epithelial cells, though this activity was unstable and decreased significantly after one week of storage. In the colon, toxin A caused secretion and shedding of surface epithelial cells without damage to crypt cells, toxin C caused only a weak secretion, and toxin B had no effect at all. In terms of immunohistochemistry, it was found that toxin A bound to the enterocytes at the tips of the villi but not to goblet and crypt cells. The complex expression or interaction of the toxins produced by Cl difficile may explain the broad spectrum of disease (diarrhoea, colitis, and pseudomembranous colitis) associated with this micro-organism.
High power heterojunction GaAs switch IC with P-1 dB of more than 38 dBm for GSM application (2002)

A high power handling of 4 W and low control voltage of +3/0 V GaAs Switch IC, available for the hand-held phone unit for GSM dual and triple mode applications, has been successfully developed. As a basic switch element, heterojunction FET technology has been applied. The optimized stacked-structure with a dual-gate-FET and a triple-gate-FET has demonstrated high linearity of Pin-Pout with a P-1 dB (Pin) of more than 38 dBm, an insertion loss of less than 0.6 dB and an isolation of more than 22 dB in a wide frequency range of 0.5 GHz to 2.0 GHz.
Combination Therapy with Flupirtine and Opioid: Open-Label Case Series in the Treatment of Neuropathic Pain Associated with Cancer (2008)

These results in humans follow animal studies that suggest a role for flupirtine in the treatment of neuropathic pain. This short duration open-label study in 10 subjects suggests that flupirtine may be useful in the treatment of neuropathic pain when used in combination with opioids.
Characterization of plasma-enhanced chemical vapor deposition carbon nanotubes by Auger electron spectroscopy (2002)

Plasma-enhanced chemical vapor deposition (PECVD) is a versatile technique for growing well-aligned, precisely patterned, multiwalled carbon nanotubes directly on substrates. We report on the characterization of PECVD deposited nanotubes using Auger Electron Spectroscopy (AES); we believe that this is the first comprehensive AES study of nanotubes and the effect of the deposition process on the substrate. The nanotubes contained well-crystallized graphitic carbon, in contrast to the amorphous/disordered carbon byproduct which is condensed on the substrate surface. By adjusting the deposition gas ratios, we show, using depth-profiled composition analysis, that it is possible to eliminate the unwanted amorphous carbon on the substrate surface. However, a 5 nm interfacial layer, which contained the plasma species, was always present on the substrate surface due to its exposure to the plasma. We could prevent the formation of this interfacial layer by shielding areas of the substrate from the plasma to achieve truly byproduct free deposition. This technique has allowed us to fabricate promising microelectronic field emission devices using vertically aligned carbon nanotubes.
Pressurized Aerosol versus Jet Aerosol Delivery to Mechanically Ventilated Patients (1990)

SUMMARY The purpose of this study was to compare deposition of aerosol to the lung from a metered-dose inhaler (MOl) and aerosol holding chamber and from a jet nebulizer in ventilator­ dependent patients. Twenty-one patients were entered into the study, all receiving assisted ventila­ tion and inhaled bronchodilators because of airflow limitation. The average age was 68 yr; there were 10 men and 11 women. The patients were randomized to receive either 4 puffs (800 J.1g) of radiolabeled fenoterol by MOl of 1.75 ml (1,750 J.1g) of radiolabeled fenoterol solution by nebulizer. Imaging of lung fields was made by a portable scintillation camera at 5-min intervals during the study. Results showed that 20 patients completed the study, 9 receiving fenoterol by MOl, and 11 by jet nebulizer. Fourwe~ excluded from analysis because of previous pneumonectomy, two from each group. Lung depositl'on measured as apercent of given dose from either system was 5.65 ± 1.09 (mean ± SEM) for MOl plus extension chamber and 1.22 ± 0.35 for jet nebulizer (p < 0.001).There­ fore, this trial shows significantly greater efficiency of aerosol deposition to the lung In ventilator­ dependent patients when using an MOl plus aerosol holding chamber than when using a jet neb­ ulizer. AM REV RESPIR DIS 1990; 141:440-444
The 11-β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor INCB13739 Improves Hyperglycemia in Patients With Type 2 Diabetes Inadequately Controlled by Metformin Monotherapy (2010)

INCB13739 added to ongoing metformin therapy was efficacious and well tolerated in patients with type 2 diabetes who had inadequate glycemic control with metformin alone. 11BetaHSD1 inhibition offers a new potential approach to control glucose and cardiovascular risk factors in type 2 diabetes.
High-efficiency Silicon Heterojunction Solar Cells: A Review (2012)

Abstract Silicon heterojunction solar cells consist of thin amorphous silicon layers deposited on crystalline silicon wafers. This design enables energy conversion efficiencies above 20% at the industrial production level. The key feature of this technology is that the metal contacts, which are highly recombination active in traditional, diffused-junction cells, are electronically separated from the absorber by insertion of a wider bandgap layer. This enables the record open-circuit voltages typically associated with heterojunction devices without the need for expensive patterning techniques. This article reviews the salient points of this technology. First, we briefly elucidate device characteristics. This is followed by a discussion of each processing step, device operation, and device stability and industrial upscaling, including the fabrication of solar cells with energy-conversion efficiencies over 21%. Finally, future trends are pointed out.
Endocytosis of liposomes containing lysosomal proteins increases intracellular protein degradation in growing L‐132 cells (1990)

We have used a new approach to test the possible participation of lysosomes in the degradation of long-lived proteins. Rat liver lysosomal proteins were introduced, via multilamellar liposomes, into L-132 cells. Viability and protein synthesis were not impaired by this treatment. The liposomal content was released into the lysosomes of the cultured cells, as revealed by ferritin uptake and electron microscopy. Degradation rates of long-lived proteins increased with the uptake of lysosomal proteases. However, the increased protein degradation of chloroquine and leupeptin, in contrast to the inhibition by these reagents of the increased protein degradation of cells 'starved' of serum (step-down conditions). This approach opens a new way of investigating the degradation of intracellular proteins in cultured cells.
Comparison of 10 influenza A (H1N1 and H3N2) haemagglutinin sequences obtained directly from clinical specimens to those of MDCK cell- and egg-grown viruses (1993)

PCR was used to amplify and sequence the complete HA1 region of the haemagglutinin (HA)-encoding genes of 10 clinical isolates of influenza virus of the H1N1 or H3N2 subtypes. These sequences were compared to those obtained from viruses isolated from the same specimens after passage in eggs and MDCK cells. Amino acid substitutions in the egg-derived HA sequences were found in nine out of the 10 specimens analysed, whereas seven out of eight of the MDCK-derived HA sequences were identical to those in the corresponding original specimens. Changes in the H1 HA occurred at residues 77a, 196 (also found in the corresponding HA from the MDCK isolate), 225, 226 and 227; changes in the H3 HA occurred at residues 137, 156, 186, 248 and 276. In addition, we have shown that an amino acid change at residue 145 in the HA of the H3 subtype that was previously demonstrated to be egg-selected is now present in circulating strains.
Processing operations with restrictions in RDBMS without external sorting: the Tetris algorithm (1999)

Most operations of the relational algebra or SQL require a sorted stream of tuples for efficient processing. Therefore, processing complex relational queries relies on efficient access to a table in some sort order. In principle, indexes could be used, but they are superior to a full table scan only if the result set is sufficiently restricted in the index attribute. We present the Tetris algorithm, which utilizes restrictions to process a table in sort order of any attribute without the need for external sorting. The algorithm relies on the space partitioning of a multidimensional access method. A sweep line technique is used to read data in sort order of any attribute, while accessing each disk page of a table only once. Results are produced earlier than with traditional sorting techniques allowing better response times for interactive applications and pipelined processing of the result set. We describe a prototype implementation of the Tetris algorithm using UB-Trees on top of Oracle 8, define a cost model and present performance measurements for some queries of the TPC-D benchmark.
Synthesis of heteroaryl 1-thio-ß-D-galactofuranosides and evaluation of their inhibitory activity towards a ß-D-galactofuranosidase (2006)

Heteroaryl 1-thio--D-galactofuranosides have been synthesized and evaluated as inhibitors of the exo--D-galactofuranosidase from Penicillium fellutanum. 2-Pyridinethiol, 4-pyridinethiol, 1methylimidazole-2-thiol, 5-methyl-1,3,4-thiadiazole-2-thiol, 2-pyrimidinethiol and 4,6-dimethyl-2-pyrimidinethiol were employed as thiols, as such heteroaromatic aglycons are expected to display particular interactions with the active site of the enzyme. These thiols were condensed with per-O-benzoyl-D-galactofuranose, in the presence of SnCl4 or BF3.OEt2, followed by Odebenzoylation under mild conditions to afford the heteroaryl 1-thio--D-galactofuranosides in high yields. The enzymatic assays showed that 4,6-dimethyl-2-pyrimidyl 1-thio--Dgalactofuranoside was the best inhibitor (IC50 135 M), considerable more potent than the analogue lacking the methyl groups in the aglycon moiety.
Combinatorial chips for optimizing the growth and integration of carbon nanofibre based devices (2003)

The growth of carbon nanofibres (CNF) by plasma enhanced chemical vapour deposition (PECVD) and the integration of CNFs into devices are studied using high throughput methodology. A growth compatibility chip containing candidate metal contact underlayers and transition metal catalyst layers are used to explore growth activity from various pairings of these two layers. In addition, catalyst density microarray chips (CDMCs) where each chip consists of catalyst patterns with various feature sizes and densities were used to investigate CNF growth and integration. The CDMCs were used to efficiently explore CNF growth conditions as well as subsequent downstream integration and testing for applications in ultrasensitive biosensing and field emission. The methodology described here is widely applicable as a general approach for optimizing the bottom-up growth and integration of nanostructures.
Human-centred approaches in slipperiness measurement (2001)

A number of human-centred methodologies--subjective, objective, and combined--are used for slipperiness measurement. They comprise a variety of approaches from biomechanically-oriented experiments to psychophysical tests and subjective evaluations. The objective of this paper is to review some of the research done in the field, including such topics as awareness and perception of slipperiness, postural and balance control, rating scales for balance, adaptation to slippery conditions, measurement of unexpected movements, kinematics of slipping, and protective movements during falling. The role of human factors in slips and falls will be discussed. Strengths and weaknesses of human-centred approaches in relation to mechanical slip test methodologies are considered. Current friction-based criteria and thresholds for walking without slipping are reviewed for a number of work tasks. These include activities such as walking on a level or an inclined surface, running, stopping and jumping, as well as stair ascent and descent, manual exertion (pushing and pulling, load carrying, lifting) and particular concerns of the elderly and mobility disabled persons. Some future directions for slipperiness measurement and research in the field of slips and falls are outlined. Human-centred approaches for slipperiness measurement do have many applications. First, they are utilized to develop research hypotheses and models to predict workplace risks caused by slipping. Second, they are important alternatives to apparatus-based friction measurements and are used to validate such methodologies. Third, they are used as practical tools for evaluating and monitoring slip resistance properties of footwear, anti-skid devices and floor surfaces.
Efficacy of Methylnaltrexone Versus Naloxone for Reversal of Morphine-Induced Depression of Hypoxic Ventilatory Response (1994)

Methylnaltrexone (MNTX) is a quaternary derivative of naltrexone. It does not cross the blood-brain barrier and, thus, it reverses peripherally mediated effects of morphine without blocking its centrally located analgesic effects. The effects of MNTX on morphine-induced depression of hypoxic ventilatory response are unknown. We evaluated the efficacy of MNTX, compared with naloxone, in reversing this effect. On three sessions separated by a week, 10 healthy male volunteers received morphine, 0.125 mg/kg, as a bolus at 20 min after completing a control hypoxic ventilatory challenge. At 60 min, naloxone, 5 micrograms/kg, MNTX, 0.3 mg/kg, or placebo was administered in a randomized double-blind order. Four isocapnic hypoxic ventilatory challenges were conducted: 0 min (control), 40 min (postmorphine), and 80 and 120 min (postreversal) and the hypoxic respiratory responses were recorded. Morphine administration was associated with a significant depression in hypoxic responses: The slope of the response (L/min/Spo2) and the predicted ventilation at 80% O2 saturation (VE80) (L/min) decreased significantly in the three sessions (P < 0.05). Naloxone injection reversed the respiratory depression at 80 min (85% of the control value of the slope and 89% of VE80), whereas MNTX and placebo did not. At 120 min, the slope (69%) and VE80 (80%) after naloxone administration were not significantly different from control. MNTX slope (69%) was not statistically different from the control, whereas VE80 (70%) was still depressed (P < 0.05). Placebo slope and VE80, at 120 min, remained lower than the control (P < 0.05). These data show that MNTX is not as effective as naloxone for reversal of morphine-mediated depression of respiration during acute hypoxia.
Alpha-skeletal muscle actin mRNA's accumulate in hypertrophied adult rat hearts. (1986)

Cardiac hypertrophy due to a chronic hemodynamic overload is accompanied by isoformic changes of two proteins of the thick filament of the sarcomere, myosin, and creatine phosphokinase. We have looked for isoactin changes, using deoxyribonucleic acid probes complementary to alpha-skeletal and alpha-cardiac actin messenger ribonucleic acids. Three groups of rats were studied at various days after application of a pressure overload (2-4 days, n = 13, 8-15 days, n = 5, and 30-40 days, n = 7) and were compared to control animals (n = 11). Whereas alpha-skeletal actin messenger ribonucleic acids were hardly detectable in the normal hearts (0.6 +/- 0.16%), they accumulated significantly in the first 4 days after the aortic stenosis (4.6 +/- 3.1%, p less than 0.001 vs. controls) and then slowly declined (8-15 days, 3.2 +/- 1.7% and 30-40 days, 1.6 +/- 0.6%, p less than 0.05 and NS vs. controls). This figure is similar to that observed in 8-day-old rats (2.27 +/- 0.3%, p less than 0.01 vs. controls). We conclude that, in rat myocardium, the expression of messenger ribonucleic acids encoding the sarcomeric actins is altered at the onset of a pressure overload hypertrophy. Although the physiological significance of isoactin changes is unknown, our results show that the thin filament participates as well as the thick filament in the response of cardiac muscle to new functional requirements.
Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A. (1992)

In the present report, we have investigated the in vitro differentiation of surface(s) sIgD+ and sIgD- human B cells into Ig-secreting cells in response to various stimuli. sIgD+ B cells homogeneously expressed some of the antigens identifying mantle zone B cells, but lacked expression of germinal center markers, thus confirming that the B cell populations positively selected on the basis of sIgD expression were highly enriched for naive B lymphocytes. Conversely, sIgD- B cells expressed some of the antigens specifically associated with germinal center B cells. T cell-independent differentiation of sIgD+ and sIgD- B cells could be achieved by simultaneous crosslinking of sIgs and CD40 in the presence of a mouse Ltk- cell line stably expressing human CDw32/Fc gamma RII (CDw32 L cells). In this experimental system, sIgD+ B cells were exclusively proned for IgM synthesis, whereas sIgD- B cells produced IgG, IgM, and IgA. Both the human and viral forms of interleukin 10 (IL-10) strongly increased the Ig secretion by sIgD+ and sIgD- B cells simultaneously activated through sIgs and CD40. IgM and IgG constituted the predominant Ig isotype produced by sIgD+ and sIgD- B cells, respectively, in response to IL-10. sIgD+ B cells could be induced for IgA synthesis upon co-culturing with transforming growth factor beta (TGF-beta) and IL-10, in the presence of an anti-CD40 monoclonal antibody presented by the CDw32 L cells. In contrast, TGF-beta suppressed the IL-10-mediated IgG, IgM, and IgA secretions by sIgD- B cells. sIgD+ B cells could not be induced for IgA synthesis by TGF-beta and IL-10 after crosslinking of their sIgs, suggesting that ligation of CD40 was one of the obligatory signals required for commitment of naive B cells to IgA secretion. Limiting dilution experiments indicated that the IgA-potentiating effect of TGF-beta was due to its capacity to increase the frequency of IgA-producing cells, most likely as a consequence of class switching. Taken together, our data strongly suggest that TGF-beta is involved in the regulation of IgA isotype selection in humans.