gebhart/patrepeval huggingface dataset:
Formulation of Fast-Release Gastroretentive Solid Dispersion of Glibenclamide with Gelucire 50/13 (2012)

Purpose: Fast-release gastroretentive solid dispersions of glibenclamide using gelucire were prepared to achieve improved bioavailability.Methods: Hot melt granulation technique was adopted to prepare solid dispersions (SDs) of glibenclamide in gelucire 50/13 and were compared with pure glibenclamide and physical mixtures of drug and gelucire using hot stage polarized microscopy, powder x-ray diffraction (PXRD), Fourier transform infrared spectroscopy FTIR, bouyancy as well as by in vitro release and in vivo studies. Further aging studies were carried out for the samples.Results: PXRD showed that glibenclamide was present in SD in an amorphous form while FTIR spectroscopy revealed the presence of hydrogen bonding in the SDs. In vitro buoyancy was found for 11 h and there was improvement in solubility and dissolution rate for all test formulations. Formulations were found to follow Zero order kinetic. During aging study, no decrease of in vitro drug dissolution was observed over 3-month period. Crystallinity in the SDs was observed following aging. A more pronounced lowering of blood glucose level in Wistar rats compared with the pure drug, suggests that the test formulations are superior.Conclusion: This study demonstrates the high potential of hot melt technique for obtaining stable fast release gastroretentive solid dispersions of poorly water soluble drug using polyglycolized glycerides as carriers.
Expression of the SM22alpha promoter in transgenic mice provides evidence for distinct transcriptional regulatory programs in vascular and visceral smooth muscle cells. (1996)

SM22alpha is a putative calcium-binding protein that is expressed in cardiac, smooth, and skeletal muscle lineages during mouse embryogenesis and in adult smooth muscle cells (SMC). To define the mechanisms that regulate smooth muscle-specific gene transcription, we isolated the SM22alpha gene and analyzed its 5'-flanking region for elements that direct smooth muscle expression in transgenic mice. Using a series of promoter deletions, a region of the SM22alpha promoter containing 445 base pairs of 5'-flanking sequence was found to be sufficient to direct the specific expression of a lacZ transgene in mouse embryos in the vascular smooth, cardiac, and skeletal muscle lineages in a temporospatial pattern similar to the endogenous SM22alpha gene. However, in contrast to the endogenous gene, transgene expression was not detected in venous, nor visceral SMCs. This SM22alpha-lacZ transgene was therefore able to distinguish between the transcriptional regulatory programs that control gene expression in vascular and visceral SMCs and revealed heretofore unrecognized differences between these SMC types. These results suggest that distinct transcriptional regulation programs control muscle gene expression in vascular and visceral SMCs.
Fast Ignition Inertial Fusion: An Introduction and Preview (2006)

The motivation for the fast ignition inertial fusion concept is presented as well as a brief synopsis of the papers contained within this dedicated issue. The papers cover a comprehensive view of the fast ignition inertial fusion field at the close of 2005, including both the present status and the future research that will exploit the next generation of facilities now under construction to investigate this emerging field of science and technology.
Heteroepitaxial wurtzite and zinc-blende structure GaN grown by reactive-ion molecular-beam epitaxy: Growth kinetics, microstructure, and properties (1993)

Reactive-ion molecular-beam epitaxy has been used to grow epitaxial hexagonal-structure α-GaN on Al2O3(0001) and Al2O3(011̄2) substrates and metastable zinc-blende-structure β-GaN on MgO(001) under the following conditions: growth temperature Ts=450–800 °C; incident N+2/Ga flux ratio JN+2/JGa=1–5; and N+2 kinetic energy EN+2=35–90 eV. The surface structure of the α-GaN films was (1×1), with an ≊3% contraction in the in-plane lattice constant for films grown on Al2O3(0001), while the β-GaN films exhibited a 90°-rotated two-domain (4×1) reconstruction. Using a combination of in situ reflection high-energy electron diffraction, double-crystal x-ray diffraction, and cross-sectional transmission electron microscopy, the film/substrate epitaxial relationships were determined to be: (0001)GaN∥ (0001)Al2O3 with [21̄1̄0]GaN∥[11̄00]Al2O3 and [11̄00]GaN∥[12̄10]Al2O3, (21̄1̄0)GaN∥(011̄2)Al2O3 with [0001]GaN∥[01̄11]Al2O3 and [01̄10]GaN∥[21̄1̄0]Al2O3, and (001)GaN∥(001)MgO with [001]GaN∥[001]MgO. Films with the lowest extended defect number densities (nd≂1010 cm−2 threading dislocations with Burgers vector a0/3&amp;lt;112̄0≳) and the smallest x-ray-diffraction ω rocking curve widths (5 min) were obtained using Al2O3(0001) substrates, Ts≥650 °C, JN+2/JGa≥3.5, and EN+2=35 eV. Higher N+2 acceleration energies during deposition resulted in increased residual defect densities. In addition, EN+2 and JN+2/JGa were found to have a strong effect on film growth kinetics through a competition between collisionally induced dissociative chemisorption of N2 and stimulated desorption of Ga as described by a simple kinetic growth model. The room-temperature resistivity of as-deposited GaN films grown at Ts=600–700 °C with EN+2=35 eV increased by seven orders of magnitude, from 10−1 to 106 Ω cm, with an increase in JN+2/JGa from 1.7 to 5.0. Hall measurements on the more conductive samples yielded typical electron carrier concentrations of 2×1018 cm−3 with mobilities of 30–40 cm2 V−1 s−1. The room-temperature optical band gaps of α-GaN and β-GaN were 3.41 and 3.21 eV, respectively.
Linear efficient antialiased displacement and reflectance mapping (2013)

We present Linear Efficient Antialiased Displacement and Reflectance (LEADR) mapping, a reflectance filtering technique for displacement mapped surfaces. Similarly to LEAN mapping, it employs two mipmapped texture maps, which store the first two moments of the displacement gradients. During rendering, the projection of this data over a pixel is used to compute a noncentered anisotropic Beckmann distribution using only simple, linear filtering operations. The distribution is then injected in a new, physically based, rough surface microfacet BRDF model, that includes masking and shadowing effects for both diffuse and specular reflection under directional, point, and environment lighting. Furthermore, our method is compatible with animation and deformation, making it extremely general and flexible. Combined with an adaptive meshing scheme, LEADR mapping provides the very first seamless and hardware-accelerated multi-resolution representation for surfaces. In order to demonstrate its effectiveness, we render highly detailed production models in real time on a commodity GPU, with quality matching supersampled ground-truth images.
Construction of l‐Lysine‐, l‐Threonine‐, or l‐Isoleucine‐Overproducing Strains of Corynebacterium glutamicum (1996)

The gram-negative bacterium Corynebacterium glutamicum is used for the industrial production of amino acids, for example, of L-glutamate and L-lysine. By cloning and expressing the various genes of the L-lysine pathway in C. glutamicum, we would demonstrate that an increase of the flux of L-aspartate semialdehyde to L-lysine could be obtained in strains with increased dihydrodipicolinate synthase activity. Recently we detected that in C. glutamicum two pathways exist for synthesis of D,L-diaminopimelate and L-lysine. Mutants defective in one pathway are still able to synthesize enough L-lysine for growth, but the L-lysine secretion is reduced to 50 to 70%. Using NMR spectroscopy, we could calculate how much of the L-lysine secreted into the medium is synthesized via either one or the other pathway. Amplification of the feedback inhibition insensitive homoserine dehydrogenase and homoserine kinase in a high L-lysine-overproducing strain enabled channeling of the carbon flow from the intermediate aspartate semialdehyde towards homoserine, resulting in a high accumulation of L-threonine. For a further flux from L-threonine to L-isoleucine, the allosteric control of threonine dehydratase was eliminated.
The neuropathology of frontotemporal lobar degeneration caused by mutations in the progranulin gene (2006)

The most common pathology in frontotemporal dementia (FTD) is tau-negative, ubiquitin-immunoreactive (ub-ir) neuronal inclusions (FTLD-U). Recently, we identified mutations in the progranulin (PGRN) gene as the cause of autosomal dominant FTLD-U linked to chromosome 17. Here, we describe the neuropathology in 13 patients from 6 different families, each with FTD caused by a different PGRN mutation. The most consistent feature was the presence of ub-ir lentiform neuronal intranuclear inclusions (NII) in the neocortex and striatum. In addition, the neocortex showed moderate-to-severe superficial laminar spongiosis, chronic degenerative changes, ub-ir neurites and well-defined ub-ir neuronal cytoplasmic inclusions (NCI). In the striatum, there were numerous ub-ir neurites. NCI in the hippocampus usually had a granular appearance. In contrast, familial FTLD-U cases without PGRN mutations had no NII, less severe neocortical and striatal pathology and hippocampal NCI that were more often solid. Eight cases in which genetic analysis was not available also had NII and an overall pathology similar to those with proven mutations. None of our cases of FTLD-U without NII showed the same pattern of pathology as those with mutations. These findings suggest that FTD caused by PGRN mutations has a recognizable pathology with the most characteristic feature being ub-ir NII.
Multiple tissues express alpha 1-antitrypsin in transgenic mice and man. (1988)

Hepatocytes are considered to be the predominant source of alpha1-antitrypsin (AAT), the major antiprotease in human plasma. The development of emphysema in the hereditary PiZ AAT deficiency state suggests that, inhibition of leukocyte elastase in the lung is a major function of this protein. In addition, patients with AAT deficiency are at increased risk for developing cholestasis in infancy and chronic liver disease as adults. The mechanism for hepatic cell injury, however, is not understood. Transgenic mice that express the normal human AAT gene demonstrate abundant AAT in hepatocytes and spe- cific cell types of numerous nonhepatic tissues. Immunoperoxi- dase techniques have previously disclosed AAT in many of the cell types seen in transgenic mice; however, the issue of local synthesis vs. endocytosis in these cell types has remained unresolved. In this study, AAT mRNA was seen in a variety of tissues in the transgenic mouse. Imimunoelectron microscopy of renal tubular and small intestinal epithelial cells in the transgenic mice demonstrated AAT within the cisternae of the rough endoplasmic reticulum, as in hepatocytes. These find- ings support the possibility of local synthesis in the various cell types. The results -suggest that in addition to maintaining tissue integrity in the lung, the protease/antiprotease balance may have physiological functions in other organs as well.
Functional Tissue Engineering: The Role of Biomechanics (2000)

"Tissue engineering" uses implanted cells, scaffolds, DNA, protein, and/or protein fragments to replace or repair injured or diseased tissues and organs. Despite its early success, tissue engineers have faced challenges in repairing or replacing tissues that serve a predominantly biomechanical function. An evolving discipline called "functional tissue engineering" (FTE) seeks to address these challenges. In this paper, the authors present principles of functional tissue engineering that should be addressed when engineering repairs and replacements for load-bearing structures. First, in vivo stress/strain histories need to be measured for a variety of activities. These in vivo data provide mechanical thresholds that tissue repairs/replacements will likely encounter after surgery. Second, the mechanical properties of the native tissues must be established for subfailure and failure conditions. These "baseline data" provide parameters within the expected thresholds for different in vivo activities and beyond these levels if safety factors are to be incorporated. Third, a subset of these mechanical properties must be selected and prioritized. This subset is important, given that the mechanical properties of the designs are not expected to completely duplicate the properties of the native tissues. Fourth, standards must be set when evaluating the repairs/replacements after surgery so as to determine, "how good is good enough?" Some aspects of the repair outcome may be inferior, but other mechanical characteristics of the repairs and replacements might be suitable. New and improved methods must also be developed for assessing the function of engineered tissues. Fifth, the effects of physical factors on cellular activity must be determined in engineered tissues. Knowing these signals may shorten the iterations required to replace a tissue successfully and direct cellular activity and phenotype toward a desired end goal. Finally, to effect a better repair outcome, cell-matrix implants may benefit from being mechanically stimulated using in vitro "bioreactors" prior to implantation. Increasing evidence suggests that mechanical stress, as well as other physical factors, may significantly increase the biosynthetic activity of cells in bioartificial matrices. Incorporating each of these principles of functional tissue engineering should result in safer and more efficacious repairs and replacements for the surgeon and patient.
Applications of Delayed Extraction Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry to Oligonucleotide Analysis (1996)

A delayed ion extraction technique is shown to dramatically improve mass resolution and the overall quality of matrix-assisted laser desorption ionization (MALDI) mass spectra of oligonucleotides. Isotope limited mass resolution was obtained on samples up to 10-kDa molecular mass in linear mode, and as high as 7500 mass resolution (defined at half peak height) was observed in reflector mode. This performance is as good as that achieved to date for peptides and proteins. Applications included the detection of oxidized byproducts of phosphorothioate DNA and separation of components differing only by 15 Da at 9.5-kDa molecular mass. In addition to single components, complex mixtures could also be analyzed at greatly improved performance over conventional MALDI. An example is shown for sequence verification of an oligonucleotide of 31 bases in length by analyzing the failure products. Mass accuracy was adequate to verify sequences of oligodeoxyribonucleotides up to 9500-Da molecular mass. Fast fragmentation taking place between the ionizing pulse and the extraction pulse is demonstrated to be a sequencing tool for small oligonucleotides. By proper selection of matrix material, wavelength, and irradiance, fast fragmentation can be promoted efficiently. Fragment ions tend to form from cleavage of phosphodiester bonds, as previously observed in infrared MALDI.
Site-specific DNA cleavage by vaccinia virus DNA topoisomerase I. Role of nucleotide sequence and DNA secondary structure (1991)

Cleavage of linear duplex DNA by purified vaccinia virus DNA topoisomerase I occurs at a conserved sequence element (5'-C/T)CCTT decreases) in the incised DNA strand. Oligonucleotides spanning the high affinity cleavage site CCCTT at nucleotide 2457 in pUC19 DNA are cleaved efficiently in vitro, but only when hybridized to a complementary DNA molecule. As few as 6 nucleotides proximal to the cleavage site and 6 nucleotides downstream of the site are sufficient to support exclusive cleavage at the high affinity site (position +1). Single nucleotide substitutions within the consensus pentamer have deleterious effects on the equilibria of the topoisomerase binding and DNA cleavage reactions. The effects of base mismatch within the pentamer are more dramatic than are the effects of mutations that preserve base complementarity. Competition experiments indicate that topoisomerase binds preferentially to DNA sites containing the wild-type pentamer element. Single-stranded DNA containing the sequence CCCTT in the cleaved stand is a more effective competitor than is single-stranded DNA containing the complementary sequence in the noncleaved strand.
Anti‐MuSK patient antibodies disrupt the mouse neuromuscular junction (2008)

IgG from anti-MuSK-positive patients can cause myasthenia gravis when injected into mice. This may be explained by a progressive reduction in the density of postsynaptic AChR combined with changes in the nerve terminal and its relation to the postsynaptic structure.
Shallow Bounding Volume Hierarchies for Fast SIMD Ray Tracing of Incoherent Rays (2008)

Abstract Photorealistic image synthesis is a computationally demanding task that relies on ray tracing for the evaluation of integrals. Rendering time is dominated by tracing long paths that are very incoherent by construction. We therefore investigate the use of SIMD instructions to accelerate incoherent rays. SIMD is used in the hierarchy construction, the tree traversal and the leaf intersection. This is achieved by increasing the arity of acceleration structures, which also reduces memory requirements. We show that the resulting hierarchies can be built quickly and are smaller than acceleration structures known so far while at the same time outperforming them for incoherent rays. Our new acceleration structure speeds up ray tracing by a factor of 1.6 to 2.0 compared to a highly optimized bounding interval hierarchy implementation, and 1.3 to 1.6 compared to an efficient k d‐tree. At the same time, the memory requirements are reduced by 10–50%. Additionally we show how a caching mechanism in conjunction with this memory efficient hierarchy can be used to speed up shadow rays in a global illumination algorithm without increasing the memory footprint. This optimization decreased the number of traversal steps up to 50%.
Stimulus Perception in Bacterial Signal-Transducing Histidine Kinases (2006)

Two-component signal-transducing systems are ubiquitously distributed communication interfaces in bacteria. They consist of a histidine kinase that senses a specific environmental stimulus and a cognate response regulator that mediates the cellular response, mostly through differential expression of target genes. Histidine kinases are typically transmembrane proteins harboring at least two domains: an input (or sensor) domain and a cytoplasmic transmitter (or kinase) domain. They can be identified and classified by virtue of their conserved cytoplasmic kinase domains. In contrast, the sensor domains are highly variable, reflecting the plethora of different signals and modes of sensing. In order to gain insight into the mechanisms of stimulus perception by bacterial histidine kinases, we here survey sensor domain architecture and topology within the bacterial membrane, functional aspects related to this topology, and sequence and phylogenetic conservation. Based on these criteria, three groups of histidine kinases can be differentiated. (i) Periplasmic-sensing histidine kinases detect their stimuli (often small solutes) through an extracellular input domain. (ii) Histidine kinases with sensing mechanisms linked to the transmembrane regions detect stimuli (usually membrane-associated stimuli, such as ionic strength, osmolarity, turgor, or functional state of the cell envelope) via their membrane-spanning segments and sometimes via additional short extracellular loops. (iii) Cytoplasmic-sensing histidine kinases (either membrane anchored or soluble) detect cellular or diffusible signals reporting the metabolic or developmental state of the cell. This review provides an overview of mechanisms of stimulus perception for members of all three groups of bacterial signal-transducing histidine kinases.
A Programmable TV Receiver (1976)

Digital circuit technique has begun to be applied to television receivers recently. Digital channel selection systems using a varactor tuner and remote control switches are two such examples.
RECESSION HEADLINE NEWS, CONSUMER SENTIMENT, THE STATE OF THE ECONOMY AND PRESIDENTIAL POPULARITY: A TIME SERIES ANALYSIS 1989–1993 (1995)

Journal Article RECESSION HEADLINE NEWS, CONSUMER SENTIMENT, THE STATE OF THE ECONOMY AND PRESIDENTIAL POPULARITY: A TIME SERIES ANALYSIS 1989–1993 Get access Deborah J. Blood, Deborah J. Blood Search for other works by this author on: Oxford Academic Google Scholar Peter C. B. Phillips Peter C. B. Phillips Search for other works by this author on: Oxford Academic Google Scholar International Journal of Public Opinion Research, Volume 7, Issue 1, SPRING 1995, Pages 2–22, https://doi.org/10.1093/ijpor/7.1.2 Published: 01 March 1995
Combined effects of prostaglandin E receptor subtype EP1 and subtype EP4 antagonists on intestinal tumorigenesis in adenomatous polyposis coli gene knockout mice (2003)

Previous studies have shown that prostaglandin E(2) (PGE(2)) is involved in intestinal carcinogenesis through its binding to the PGE(2) receptor subtypes EP(1) and EP(4) and activation of downstream pathways. ONO-8711 and ONO-AE2-227, prostaglandin E receptor subtype EP(1)- and EP(4)-selective antagonists, respectively, are known to suppress formation of intestinal polyps in adenomatous polyposis coli gene-deficient mice. The present study was designed to investigate the combined effects of EP(1) and EP(4) antagonists on spontaneous polyp formation in APC1309 mice in order to determine the contribution of each receptor to intestinal tumorigenesis. APC1309 mice were treated with 400 ppm of ONO-8711 alone, 400 ppm of ONO-AE2-227 alone or both in combination in the diet for 6 weeks. The mean area of polyps found in the intestine, calculated as the longer diameter x the shorter diameter x pi, was reduced by 12%, 43% (P < 0.01) and 56% (P < 0.01) of the mean control value (8.8 mm(2)) in the ONO-8711 alone, ONO-AE2-227 alone and combination treatment groups, respectively, suggesting clear additive effects of the combination. The same additive tendency for suppression was also observed with respect to the numbers of polyps in the intestine. Polyp size reduction was more remarkable with the EP(4) antagonist, while the number reduction was more pronounced with the EP(1) antagonist. Our results indicate that EP(1) and EP(4) may have separate intrinsic roles and, to some extent, contribute to polyp formation independently. Thus, combination treatment has potential for the chemoprevention of colon carcinogenesis.
An expectation-maximization algorithm for probabilistic reconstructions of full-length isoforms from splice graphs (2006)

Reconstructing full-length transcript isoforms from sequence fragments (such as ESTs) is a major interest and challenge for bioinformatic analysis of pre-mRNA alternative splicing. This problem has been formulated as finding traversals across the splice graph, which is a directed acyclic graph (DAG) representation of gene structure and alternative splicing. In this manuscript we introduce a probabilistic formulation of the isoform reconstruction problem, and provide an expectation-maximization (EM) algorithm for its maximum likelihood solution. Using a series of simulated data and expressed sequences from real human genes, we demonstrate that our EM algorithm can correctly handle various situations of fragmentation and coupling in the input data. Our work establishes a general probabilistic framework for splice graph-based reconstructions of full-length isoforms.