gebhart/patrepeval huggingface dataset:
The use of agalsidase alfa enzyme replacement therapy in the treatment of Fabry disease (2009)

Clinical trials data, along with experience of the treatment collected through participation of treating physicians in a world-wide Fabry disease registry, have demonstrated that it improves pain and stabilizes renal function, as well as cardiomyopathy, in some patients. More data are needed to evaluate the role of treatment with this drug in the prevention of stroke and adverse cardiac events, and its overall effect on the lifespan and quality of life of affected individuals.
Neurotoxicity of NMDA receptor antagonists: an overview. (1994)

The glutamate transmitter system provides several benevolent/malevolent paradoxes. Glutamate itself serves vitally important functions in the CNS but has enormous neurodestructive potential. NMDA glutamate receptor antagonists protect many neurons against glutamate neurotoxicity, while injuring or destroying certain other neurons and inducing psychotic symptoms and memory impairment. Therefore, the challenge in developing protective therapies against glutamate's neurodestructive potential is to find benevolent agents that are not malevolent as well. There are two possible approaches. One is to develop neuroprotective agents that are free from neuropsychopathological side effects; the other is to use NMDA antagonists even though they have neuropsychopathological side effects, but to use them in combination with other agents that block the side effects without producing side effects of their own.
Role of Modulators in Controlling the Colloidal Stability and Polydispersity of the UiO-66 Metal–Organic Framework (2017)

Nanoscale UiO-66 Zr<sub>6</sub>(OH)<sub>4</sub>O<sub>4</sub>(C<sub>8</sub>O<sub>4</sub>H<sub>4</sub>)<sub>6</sub> has been synthesized with a series of carboxylic acid modulators, R-COOH (where R = H, CH<sub>3</sub>, CF<sub>3</sub>, and CHCl<sub>2</sub>). The phase purity and size of each MOF was confirmed by powder X-ray diffraction, BET surface area analysis, and scanning transmission electron microscopy (STEM). Size control of UiO-66 crystals from 20 nm to over 1 μm was achieved, and confirmed by STEM. The colloidal stability of each MOF was evaluated by dynamic light scattering and was found to be highly dependent on the modulator conditions utilized in the synthesis, with both lower pKa and higher acid concentration resulting in more stable structures. Furthermore, STEM was carried out on both colloidally stable samples and those that exhibited a large degree of aggregation, which allowed for visualization of the different degrees of dispersion of the samples. The use of modulators at higher concentrations and with lower pK<sub>a</sub>s leads to the formation of more defects, as a consequence of terephthalic acid ligands being replaced by modulator molecules, thereby enhancing the colloidal stability of the UiO-66 nanoparticles. These findings could have a significant impact on nanoscale MOF material syntheses and applications, especially in the areas of catalysis and drug delivery.
A Highly Active Manganese Precatalyst for the Hydrosilylation of Ketones and Esters (2013)

The reduction of ((Ph2PPr)PDI)MnCl2 allowed the preparation of the formally zerovalent complex, ((Ph2PPr)PDI)Mn, which features a pentadentate bis(imino)pyridine chelate. This complex is a highly active precatalyst for the hydrosilylation of ketones, exhibiting TOFs of up to 76,800 h(-1) in the absence of solvent. Loadings as low as 0.01 mol % were employed, and ((Ph2PPr)PDI)Mn was found to mediate the atom-efficient utilization of Si-H bonds to form quaternary silane products. ((Ph2PPr)PDI)Mn was also shown to catalyze the dihydrosilylation of esters following cleavage of the substrate acyl C-O bond. Electronic structure investigation of ((Ph2PPr)PDI)Mn revealed that this complex possesses an unpaired electron on the metal center, rendering it likely that catalysis takes place following electron transfer to the incoming carbonyl substituent.
Antimicrobial Activity of Topical Skin Pharmaceuticals – An In vitro Study (2010)

The aim of this study was to investigate the antimicrobial activity of currently available topical skin pharmaceuticals against Candida albicans, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes. The agar dilution assay was used to determine the minimal inhibitory concentration for cream formulations and their active substances. Corticosteroid formulations with the antiseptics clioquinol or halquinol were active against all microbes. The hydrogen peroxide formulation was primarily active against staphylococci. Clotrimazole, miconazole and econazole showed an effect against staphylococci in addition to their effect on C. albicans. In contrast, terbinafine had no antibacterial effect. Fusidic acid was active against staphylococci, with slightly weaker activity against S. pyogenes and no activity against C. albicans or E. coli. In summary, some topical skin pharmaceuticals have broad antimicrobial activity in vitro, clioquinol and halquinol being the most diverse. In limited superficial skin infection topical treatment can be an alternative to systemic antibiotics and should be considered. With the global threat of multi-resistant bacteria there is a need for new, topical, non-resistance-promoting, antimicrobial preparations for the treatment of skin infections.
Vertically integrated Josephson circuits with stacked Nb/Alo<inf>x</inf>/Nb junctions (1987)

Since Josephson circuit has a multi-layered wiring structure, planarization is necessary for fabricating integrated Josephson circuits. We used bias-sputtered SiO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> films as the insulators in Josephson circuits for planarization. By using with bias-sputtered SiO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> films, the surface on the junctions becomes smooth. The planarized junctions show the good I-V characteristics such as a gap voltage of 2.9 mV and a Vm of over 50 mV. In addition, we stacked another Josephson junction above the planarized junction. We obtained a high quality junction with the same gap voltage and Vm as the lower junctions. Bias-sputtered SiO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> films are effective for the planarization of Josephson circuits, and makes it possible to fabricate three-dimensional integrated circuits.
A dual role for the cAMP-dependent protein kinase in tyrosine hydroxylase gene expression. (1993)

Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine to 3,4-dihydroxy-L-phenylalanine, the first and rate-limiting step in catecholamine biosynthesis. The cAMP-dependent protein kinase (PKA) phosphorylates and activates the TH enzyme and is thought to mediate transcriptional induction of the TH gene. To better understand the functional role of PKA in TH gene regulation, we studied TH gene expression at the transcriptional, translational, and post-translational levels in several PKA-deficient cell lines derived from rat PC12 pheochromocytoma cells. Strikingly, all PKA-deficient cell lines analyzed in this study showed substantial deficits in basal TH expression as measured by TH enzymatic activity, level of TH immunoreactivity, TH protein level, and steady-state mRNA level. Interestingly, the steady-state level of mRNA correlated well with levels of TH activity, immunoreactivity, and protein. In addition, PKA-deficient cell lines lacked transcriptional induction of the TH gene following treatment with dibutyryl cAMP. Cotransfection of PKA-deficient cells with an expression plasmid for the catalytic subunit of PKA fully reversed transcriptional defect, as indicated by robust transcriptional induction of a reporter construct containing 2400 bp of TH upstream sequence in all PC12 cells tested. These data indicate that the PKA system regulates both the basal and the cAMP-inducible expression of the TH gene primarily at the transcriptional level in PC12 cells.
Subwavelength cylindrical grating by holistic phase-mask coordinate transform (2012)

A periodic grating with an integer number of periods is fabricated at the resist-coated wall of a cylinder by exposing a circularly symmetrical planar high index phase mask to a cylindrical wave. This extends the spatial coherence features easily achievable in a planar 2D space to the 3D space of cylindrical waves and elements.
Advances in the design of macroporous polymer scaffolds for potential applications in dentistry (2013)

A paradigm shift is taking place in medicine and dentistry from using synthetic implants and tissue grafts to a tissue engineering approach that uses degradable porous three-dimensional (3D) material hydrogels integrated with cells and bioactive factors to regenerate tissues such as dental bone and other oral tissues. Hydrogels have been established as a biomaterial of choice for many years, as they offer diverse properties that make them ideal in regenerative medicine, including dental applications. Being highly biocompatible and similar to native extracellular matrix, hydrogels have emerged as ideal candidates in the design of 3D scaffolds for tissue regeneration and drug delivery applications. However, precise control over hydrogel properties, such as porosity, pore size, and pore interconnectivity, remains a challenge. Traditional techniques for creating conventional crosslinked polymers have demonstrated limited success in the formation of hydrogels with large pore size, thus limiting cellular infiltration, tissue ingrowth, vascularization, and matrix mineralization (in the case of bone) of tissue-engineered constructs. Emerging technologies have demonstrated the ability to control microarchitectural features in hydrogels such as the creation of large pore size, porosity, and pore interconnectivity, thus allowing the creation of engineered hydrogel scaffolds with a structure and function closely mimicking native tissues. In this review, we explore the various technologies available for the preparation of macroporous scaffolds and their potential applications.
Impact of the Environmental Low-Level Wind Profile on Ensemble Forecasts of the 4 May 2007 Greensburg, Kansas, Tornadic Storm and Associated Mesocyclones (2011)

The early tornadic phase of the Greensburg, Kansas, supercell on the evening of 4 May 2007 is simulated using a set of storm-scale (1-km horizontal grid spacing) 30-member ensemble Kalman filter (EnKF) data assimilation and forecast experiments. The Next Generation Weather Radar (NEXRAD) level-II radar data from the Dodge City, Kansas (KDDC), Weather Surveillance Radar-1988 Doppler (WSR-88D) are assimilated into the National Severe Storms Laboratory (NSSL) Collaborative Model for Multiscale Atmospheric Simulation (COMMAS). The initially horizontally homogeneous environments are initialized from one of three reconstructed soundings representative of the early tornadic phase of the storm, when a low-level jet (LLJ) was intensifying. To isolate the impact of the low-level wind profile, 0–3.5-km AGL wind profiles from Vance Air Force Base, Oklahoma (KVNX), WSR-88D velocity-azimuth display (VAD) analyses at 0130, 0200, and 0230 UTC are used. A sophisticated, double-moment bulk ice microphysics scheme is employed. For each of the three soundings, ensemble forecast experiments are initiated from EnKF analyses at various times prior to and shortly after the genesis of the Greensburg tornado (0200 UTC). Probabilistic forecasts of the mesocyclone-scale circulation(s) are generated and compared to the observed Greensburg tornado track. Probabilistic measures of significant rotation and observation-space diagnostic statistics are also calculated. It is shown that, in general, the track of the Greensburg tornado is well predicted, and forecasts improve as forecast lead time decreases. Significant variability is also seen across the experiments using different VAD wind profiles. Implications of these results regarding the choice of initial mesoscale environment, as well as for the “Warn-on-Forecast” paradigm for probabilistic numerical prediction of severe thunderstorms and tornadoes, are discussed.
Gene Replacement Analysis of the <i>Streptomyces virginiae barA</i> Gene Encoding the Butyrolactone Autoregulator Receptor Reveals that BarA Acts as a Repressor in Virginiamycin Biosynthesis (1998)

Virginiae butanolides (VBs), which are among the butyrolactone autoregulators of Streptomyces species, act as a primary signal in Streptomyces virginiae to trigger virginiamycin biosynthesis and possess a specific binding protein, BarA. To clarify the in vivo function of BarA in the VB-mediated signal pathway that leads to virginiamycin biosynthesis, two barA mutant strains (strains NH1 and NH2) were created by homologous recombination. In strain NH1, an internal 99-bp EcoT14I fragment of barA was deleted, resulting in an in-frame deletion of 33 amino acid residues, including the second helix of the probable helix-turn-helix DNA-binding motif. With the same growth rate as wild-type S. virginiae on both solid and liquid media, strain NH1 showed no apparent changes in its morphological behavior, indicating that the VB-BarA pathway does not participate in morphological control in S. virginiae. In contrast, virginiamycin production started 6 h earlier in strain NH1 than in the wild-type strain, demonstrating for the first time that BarA is actively engaged in the control of virginiamycin production and implying that BarA acts as a repressor in virginiamycin biosynthesis. In strain NH2, an internal EcoNI-SmaI fragment of barA was replaced with a divergently oriented neomycin resistance gene cassette, resulting in the C-terminally truncated BarA retaining the intact helix-turn-helix motif. In strain NH2 and in a plasmid-integrated strain containing both intact and mutated barA genes, virginiamycin production was abolished irrespective of the presence of VB, suggesting that the mutated BarA retaining the intact DNA-binding motif was dominant over the wild-type BarA. These results further support the hypothesis that BarA works as a repressor in virginiamycin production and suggests that the helix-turn-helix motif is essential to its function. In strain NH1, VB production was also abolished, thus indicating that BarA is a pleiotropic regulatory protein controlling not only virginiamycin production but also autoregulator biosynthesis.
A solid state paramagnetic resonance spectrometer (1957)

A spectrometer is described for use in the frequency range 9000 to 10 000 Mc/s and at the fixed temperatures of boiling refrigerants and a small range below obtained by pumping on the liquid. The lowest temperature available is the triple point of hydrogen (14°K). A high sensitivity is achieved by modulating the magnetic field at 115 kc/s. The sensitivity is such that 1013 atoms of 56Co have been detected at 20°K with a signal/noise ratio of 3: 1; it is estimated that 2 × 10-11 moles of the free radical diphenyltrinitro phenyl hydrazyl (DPPH) would be detectable at 290°K.
Recent Developments in Polyurethanes and Poly(acrylates) Interpenetrating Polymer Networks (2003)

Abstract Owing to the great versatility offered by polyurethanes regarding the ease of synthesis and variable properties of the final product obtained (elastomeric or rigid polymer), polyurethanes become a basic component used in IPN formation. Numerous studies were conducted on IPNs based on polyurethanes and various vinyl monomers. Tensile strength, hardness, swelling, and thermal properties were obtained, and morphology studies have been conducted. This review gives a comprehensive compilation of the recent studies on these properties. The article specifically deals with the systematic coverage of all the research work carried out in the field of interpenetrating polymer networks (IPNs) based on polyurethanes (PUs) and various vinyl monomers.
Reservable Transactions: An Approach for Reliable Multidatabase Transaction Management (1992)

Atomically committing global transactions in a multidatabase system is difficult beca.use of local system autonomy. Traditional tra.nsaction management methods, such as two phase commit (2PC), are often not possible, since many database systems do not support a (visible) prepare-to-commlt state. And, even where the local database systems of a multidatabase do provide such support, the potential blocking and long dela.ys of 2PC can severly degrade local execution autonomy. Transaction models that use compensation (such as Sagas), can avoid some of these problems, however these methods are only appropriate for certain cases. This paper presents reservable transactions, which contain a reservation phase that utilizes data semantics to ensure that a transaction can commit, without completely blocking the data. that the transaction accesses. The method presented can handle cases where compensation is not applicable. In addition, the reservation concept can be used to jncrease the cases where compensation is applicable. ·This research is funded by the Indiana Corporation for Science and Technology (CST), a PYI Award from NSF under grant IRI-8857952, a Graduate Student Researcher Program (GSRP) grant from NASA, and grants from the AT&T Foundation, Tektronix, SERC, Mobil Oil and Bell Northern Research.
Ras and Signal Transducer and Activator of Transcription (STAT) Are Essential and Sufficient Downstream Components of <i>Janus</i> Kinases in Cell Proliferation (2000)

Cytokines exert their activities in cell growth and differentiation by binding specific cell membrane receptors. Janus kinases (JAKs) are cytoplasmic protein tyrosine kinases that physically interact with intracellular domains of the cytokine receptors and they play crucial roles in transducing signals triggered by the cytokine-receptor interaction. We have previously shown that conditional activation of JAK through membrane-proximal dimerization confers cytokine-independence on interleukin-3 (IL-3)-dependent Ba / F3 lymphoid cells and that the cytokine-independent proliferation is completely inhibited by dominant negative Ras. In this work, we demonstrate that ectopic expression of a dominant negative form of Stat5, a major signal transducer and activator of transcription (STAT) expressed in Ba / F3 cells, also inhibits JAK-triggered mitogenesis. In contrast, overexpression of constitutively active Ras or conditional activation of Stat5 by chemical dimerization fails to confer cytokine-independence. However, concomitant activation of ectopic Ras and Stat5 molecules in Ba / F3 cells suffices for cell proliferation in the absence of IL-3. Our results indicate that Ras and STAT are essential and sufficient components of JAK-triggered mitogenesis. Our findings further indicate that the cytokine signal bifurcates into Ras and STAT pathways following JAK activation.
Cell cycle and cell death in disease: past, present and future (2010)

Cell division and cell death are the two predominant physiological processes that regulate tissue homeostasis in the adult organism. The importance of dysregulation of these processes in the pathogenesis of major diseases, such as cancer, myocardial infarction, stroke, atherosclerosis, infection, inflammation and neurodegenerative disorders, is becoming increasingly evident. Hence, attempts to find modulators of the cell cycle and cell death programmes are being made with the hope of creating novel therapeutic approaches to the treatment of these diseases. It is clear that improved understanding of how cells balance life-and-death processes is crucial for this development. In view of this, a Nobel Symposium entitled 'The Cell Cycle and Apoptosis in Disease' was organized in conjunction with the celebration of the 200-year anniversary of the Karolinska Institute in 2010. The symposium focused on the importance of dysregulation of cell cycle/cell death programmes in the pathogenesis of human disease. Three comprehensive reviews based on presentations at this symposium are presented in this issue of the Journal of Internal Medicine. They include a discussion of autophagy in anticancer therapy, the description of a role for type 2 transglutaminase in Huntington's disease and the proposal that 'redox-sensing' mechanisms might act as an orthogonal control in cell cycle and apoptosis signalling.
Real-Time Obstacle Avoidance Using Potential Field for a Nonholonomic Vehicle (2010)

In this chapter, a practical method of local obstacle avoidance for a nonholonomic vehicle with rectangular body has been proposed. Simple potential field directly using local sensor data is applied. Repulsive forces according to distances between obstacles and vehicle's body are generated at either front or rear point of action on the vehicle and their forces are treated like a lever. Both motion constraint and shape of a vehicle can be considered by this simple idea. Simulation results for various situations and experimental results by a wheelchair have proved effectiveness of our algorithm. Although this method has a disadvantage of local minima as well as general potential field method, it is intended for practical use because adequate path for local obstacle avoidance can be obtained with a little computing power. Furthermore, this algorithm may be applied to not only vehicles with two independently driven wheels but also car-like vehicles. Some improvements of the intelligent wheelchair such as 3D obstacle sensing and haptic joystick for obstacle avoidance, and consideration about general shape of vehicles are remained for our further works.
Structure of a naturally occurring plasmid with genes for enterotoxin production and drug resistance (1981)

A physical map of the 117-kilobase conjugative plasmid pCG86 was constructed using electron microscope heteroduplex analysis. This plasmid carries the genes elt, for heat-labile enterotoxin, and estA, for heat-stable enterotoxin, as well as the genes for resistance to tetracycline, streptomycin, sulfonamides, and mercury. These genes were mapped using deletions and Tn5 insertions as physical markers. Analysis of a heteroduplex between pCG86 and a previously described enterotoxin plasmid (EntP307) showed a 48-kilobase region of complete homology which included the genes elt and estA. An 8.8-kilobase BamHI fragment of EntP307 carrying elt, cloned by others, was also shown to be completely homologous with pCG86. The position of elt on the fragment was verified, and it was shown to carry estA as well. A 44-kilobase region of pCG86 showed partial homology with the region of EntP307 previously shown to contain conjugal transfer genes. The gene for tetracycline resistance is carried on a stem-loop structure with the dimensions of Tn10, and the genes for the other drug resistance markers are carried on a 14.6-kilobase segment that forms an insertion loop in heteroduplexes with EntP307. These studies suggest that pCG86 arose either by recombination between an enterotoxin plasmid of incompatibility group FI, like EntP307, and a multiple resistance factor of incompatibility group FII, or by transposition into EntP307 of two transposons.