gebhart/patrepeval huggingface dataset:
NADPH Oxidases Regulate CD44 and Hyaluronic Acid Expression in Thrombin-treated Vascular Smooth Muscle Cells and in Atherosclerosis (2010)

The intracellular signaling events by which NADPH oxidase-generated reactive oxygen species (ROS) modulate vascular smooth muscle cell (VSMC) function and atherogenesis are yet to be entirely elucidated. We previously demonstrated that NADPH oxidase deficiency decreased atherosclerosis in apoE(-/-) mice and identified adhesion protein CD44 as an important ROS-sensitive gene expressed in VSMC and atherosclerotic lesions. Here, we examined the molecular mechanisms by which NADPH oxidase-generated ROS regulate the expression of CD44 and its principal ligand, hyaluronan (HA), and how CD44-HA interaction affects VSMC proliferation and migration and inflammatory gene expression in apoE(-/-) mice aortas. Thrombin-induced CD44 expression is mediated by transcription factor AP-1 in a NADPH oxidase-dependent manner. NADPH oxidase-mediated ROS generation enhanced thrombin-induced HA synthesis, and hyaluronan synthase 2 expression in VSMC. Hyaluronidase, which generates low molecular weight HA (LMW-HA), is induced in VSMC in a NADPH oxidase-dependent manner and LMW-HA stimulated ROS generation and cell proliferation in wild-type but not p47(phox-/-) VSMC, effects that were enhanced by thrombin pretreatment. Haptotactic VSMC migration toward HA was increased by thrombin in a CD44-dependent manner. HA expression in atherosclerotic lesions and plasma-soluble CD44 and HA levels were higher in apoE(-/-) compared with apoE(-/-)/p47(phox-/-) mice. HA-regulated pro-inflammatory gene expression was higher in apoE(-/-) than apoE(-/-)/p47(phox-/-) mouse aortas. GKT136901, a specific inhibitor of Nox1- and Nox4-containing NADPH oxidase activity, attenuated ROS generation and atherosclerosis and decreased CD44 and HA expression in atherosclerotic lesions. Together, these data suggest that increased CD44 and HA expression and CD44-HA-dependent gene regulation may play a role in atherosclerosis stimulated by NADPH oxidase activation.
Optical Deconstruction of Parkinsonian Neural Circuitry (2009)

Deep brain stimulation (DBS) is a therapeutic option for intractable neurological and psychiatric disorders, including Parkinson's disease and major depression. Because of the heterogeneity of brain tissues where electrodes are placed, it has been challenging to elucidate the relevant target cell types or underlying mechanisms of DBS. We used optogenetics and solid-state optics to systematically drive or inhibit an array of distinct circuit elements in freely moving parkinsonian rodents and found that therapeutic effects within the subthalamic nucleus can be accounted for by direct selective stimulation of afferent axons projecting to this region. In addition to providing insight into DBS mechanisms, these results demonstrate an optical approach for dissection of disease circuitry and define the technological toolbox needed for systematic deconstruction of disease circuits by selectively controlling individual components.
Altered expression of transforming growth factor-beta in Alzheimer's disease (1995)

We compared immunohistochemical expression of the transforming growth factor-betas (TGF-beta 1, TGF-beta 2, and TGF-beta 3) using brain tissue from patients with nondominantly inherited Alzheimer's disease (NDAD) (n = 9), autosomal dominantly inherited Alzheimer's disease with linkage to 14q24.3 (FAD-14) (n = 4), and cognitively normal controls (n = 10) to determine whether their pathologic changes are associated with an altered distribution of the TGF-betas. We found increased expression of TGF-beta 2 in large, tangle-bearing neurons with widespread staining of glia in NDAD and FAD-14 patients compared with control cases. This result was confirmed with sandwich ELISA assays of brain tissue, which showed TGF-beta 2 levels in AD and NDAD to average 3.2 times the average level of control cases. Despite proximity of TGF-beta 1 and TGF-beta 3 to the sites of susceptibility loci on chromosomes 19 and 14, we did not find that TGF-beta 1 and TGF-beta 3 were selectively altered in any AD subtypes. However, selective induction of TGF-beta 2 may occur in NDAD and FAD-14.
DFT Study of the Role of Al3+ in the Fast Ion-Conductor Li7–3xAl3+xLa3Zr2O12 Garnet (2014)

We investigate theoretically the site occupancy of Al<sup>3+</sup> in the fast-ion-conducting cubic-garnet Li<sub>7-3<i>x</i></sub> Al<sup>3+</sup><sub><i>x</i></sub> La<sub>3</sub>Zr<sub>2</sub>O<sub>12</sub> (<i>Ia</i>-3<i>d)</i> using density functional theory. By comparing calculated and measured <sup>27</sup>Al NMR chemical shifts an analysis shows that Al<sup>3+</sup> prefers the tetrahedrally coordinated 24<i>d</i> site and a distorted 4-fold coordinated 96<i>h</i> site. The site energies for Al<sup>3+</sup> ions, which are slightly displaced from the exact crystallographic sites (i.e., 24<i>d</i> and 96<i>h</i>), are similar leading to a distribution of slightly different local oxygen coordination environments. Thus, broad <sup>27</sup>Al NMR resonances result reflecting the distribution of different isotropic chemical shifts and quadrupole coupling constants. From an energetic point of view, there is evidence that Al<sup>3+</sup> could also occupy the 48<i>g</i> site with its almost regular octahedral coordination sphere. Although this has been reported by neutron powder diffraction, the NMR chemical shift calculated for such an Al<sup>3+</sup> site has not been observed experimentally.
Six-DoF Haptic Rendering of Contact Between Geometrically Complex Reduced Deformable Models (2008)

Real-time evaluation of distributed contact forces between rigid or deformable 3D objects is a key ingredient of 6-DoF force-feedback rendering. Unfortunately, at very high temporal rates, there is often insufficient time to resolve contact between geometrically complex objects. We propose a spatially and temporally adaptive approach to approximate distributed contact forces under hard real-time constraints. Our method is CPU based, and supports contact between rigid or reduced deformable models with complex geometry. We propose a contact model that uses a point-based representation for one object, and a signed-distance field for the other. This model is related to the voxmap pointshell method (VPS), but gives continuous contact forces and torques, enabling stable rendering of stiff penalty-based distributed contacts. We demonstrate that stable haptic interactions can be achieved by point-sampling offset surfaces to input "polygon soup'' geometry using particle repulsion. We introduce a multi-resolution nested pointshell construction which permits level-of-detail contact force computation, and enables contact graceful degradation in close-proximity scenarios. Parametrically deformed distance fields are proposed to support contact between reduced deformable objects. We present several examples of 6-DoF haptic rendering of geometrically complex rigid and deformable objects in distributed contact at real-time kilohertz rates.
Chlamydia trachomatis pneumonia in the severe combined immunodeficiency (SCID) mouse. (1994)

We have developed a model of pneumonia caused by the mouse pneumonitis agent (MoPn, murine Chlamydia trachomatis) in the C.B-17 severe combined immunodeficiency (SCID) mouse. In contrast to our prior models in the nude athymic (nu/nu) and heterozygous (nu/+) mouse, SCID mice lack B-cell function and gamma delta T-cell function. SCID mice were more susceptible to MoPn than nu/nu or nu/+ mice both by criteria of mortality and quantitative lung culture. SCID mice could be reconstituted with thymocytes to be more resistant to MoPn (in the absence of significant antibody production), but the protection was modest and less than that in T-cell reconstituted nu/nu mice in our previous studies. A nu/+ MoPn-specific T-cell clone with a Th1-like cytokine profile also provided modest but significant protection without significant antibody production. The SCID mouse is a useful model to study T-cell-mediated immunity to MoPn in a B cell and gamma delta T-cell-deficient environment.
Ultra-Fast Characterization of Transient Gate Oxide Trapping in SiC Mosfets (2007)

One of the most important issues that limits the performance and reliability of SiC power MOSFETs is the threshold voltage and drain current instability under normal operation conditions. This phenomenon has been recently studied using conventional dc measurements. In this work, the authors studied the threshold voltage and drain current instability in state-of-the-art 4H-SiC MOSFETs using fast I-V measurements. Fast I-V measurements reveal the full extent of the instability, underestimated by the dc measurements. Furthermore, fast measurements allow the separation of negative and positive bias stress effects. Post oxidation annealing in NO was found to passivate the oxide traps and dramatically reduce instability. A physical model involving fast transient charge trapping and de-trapping at and near the SiC/SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> interface is proposed.
Detoxification of organophosphate nerve agents by immobilized Escherichia coli with surface‐expressed organophosphorus hydrolase (1999)

An improved whole-cell technology for detoxifying organophosphate nerve agents was recently developed based on genetically engineered Escherichia coli with organophosphorus hydrolase anchored on the surface. This article reports the immobilization of these novel biocatalysts on nonwoven polypropylene fabric and their applications in detoxifying contaminated wastewaters. The best cell loading (256 mg cell dry weight/g of support or 50 mg cell dry weight/cm2 of support) and subsequent hydrolysis of organophosphate nerve agents were achieved by immobilizing nongrowing cells in a pH 8, 150 mM citrate-phosphate buffer supplemented with 1 mM Co2+ for 48 h via simple adsorption, followed by organophosphate hydrolysis in a pH 8, 50 mM citrate-phosphate buffer supplemented with 0.05 mM Co2+ and 20% methanol at 37°C. In batch operations, the immobilized cells degraded 100% of 0.8 mM paraoxon, a model organophosphate nerve agent, in approximately 100 min, at a specific rate of 0.160 mM min−1 (g cell dry wt)−1. The immobilized cells retained almost 100% activity during the initial six repeated cycles and close to 90% activity even after 12 repeated cycles, extending over a period of 19 days without any nutrient supplementation. In addition to paraoxon, other commonly used organophosphates, such as diazinon, coumaphos, and methylparathion were hydrolyzed efficiently. The cell immobilization technology developed here paves the way for an efficient, simple, and cost-effective method for detoxification of organophosphate nerve agents. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 63: 216–223, 1999.
Fluorescence holography with improved signal-to-noise ratio by near image plane recording (2012)

Holographic fluorescence imaging is very promising, as it can obtain three-dimensional fluorescence imaging without scanning. However, the current method usually records holograms far from the image plane, with the fluorescence decaying when spreading broadly. Here we show that the signal-to-noise ratio (SNR) of fluorescence holography can be improved by recording the high-contrast interferogram near the image plane. We found that this can be achieved by setting the focal length of the lens for the reference wave (f(2)) close to that for the object wave (f(1)). With experiments, we demonstrate an example of an increase of about 21 times in SNR by changing f(2) from infinity to 226 mm, which is close to f(1) (323 mm).
Invariant V 7.2-J 33 TCR is expressed in human kidney and brain tumors indicating infiltration by mucosal-associated invariant T (MAIT) cells (2008)

The anti-tumor response of human invariant NKT (NKT) cells is well established. A novel T cell subset, mucosal-associated invariant T (MAIT) cells, possesses similar regulatory properties to NKT cells in autoimmune models and disease. Here, we examined the clonality of four T cell subsets expressing invariant alphaTCR, including Valpha7.2-Jalpha33 of MAIT cells, in 19 kidney and brain tumors. The MAIT clonotype was identified and co-expressed with NKT clonotype in half of the tumors. In contrast, two other invariant T cell clonotypes (Valpha4 and Valpha19) were not present in tumors. Such tumors also expressed Vbeta2 and Vbeta13, the restricted TCRbeta chain of MAIT cells and the antigen-presenting molecule MR1. A high percentage of infiltrating T cells was CD8+ and expressed HLA-DR suggesting activation. Although the MAIT alphaTCR was identified in both peripheral CD56+ and CD56- subsets, infiltrating lymphocytes were CD56 negative. The clonal presence of MAIT cells in tumors correlated with the expression of pro-inflammatory cytokines but no IL-4, IL-5 and IL-10, suggesting that a pro-inflammatory subset of human MAIT cells may exist. Our data imply that a CD56- subset of MAIT cells may participate in tumor immune responses similarly to NKT cells.
Synthesis of phorbol C-ring analogs: a biomimetic model study on the phorbol to 12-hydroxydaphnetoxin conversion. (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of phorbol C-ring analogs: a biomimetic model study on the phorbol to 12-hydroxydaphnetoxin conversion.Sharad S. Magar, R. C. Desai, and P. L. FuchsCite this: J. Org. Chem. 1992, 57, 20, 5360–5369Publication Date (Print):September 1, 1992Publication History Published online1 May 2002Published inissue 1 September 1992https://pubs.acs.org/doi/10.1021/jo00046a017https://doi.org/10.1021/jo00046a017research-articleACS PublicationsRequest reuse permissionsArticle Views864Altmetric-Citations27LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Synthesis of Natural and Modified Trapoxins, Useful Reagents for Exploring Histone Deacetylase Function (1996)

Trapoxin, a cyclotetrapeptide isolated from the fungus Helicoma ambiens, profoundly affects mammalian cell growth and morphology. In this paper, we describe syntheses of trapoxin, [3H]trapoxin, and K-trap, a trapoxin-based affinity reagent. These reagents have allowed us to achieve the first molecular characterization of histone deacetylase, trapoxin's cellular target.
SYNTHESIS AND STEREOCHEMISTRY OF 1-OXA-6-HETERASPIRO[2.5]OCTANES. SINGLE-CRYSTAL ANALYSIS OF 6-PHENYL-1-OXA-6-PHOSPHASPIRO[2.5]OCTANE 6-SULFIDE (1984)

Abstract The synthesis of several 1-oxa-6-heteraspiro[2.5]octanes is reported herein for the first time. Stereochemical analysis via NMR studies and a single crystal X-ray diffraction analysis of 6-phenyl-1-oxa-6-phosphaspiro[2.5]octane 6-sulfide have been completed and provide the basis for correlations of structures for other members of the families yet unknown. Epoxidation of cis-2,6-diphenyl-4-thianone with dimethyl-oxosulfonium methylide in DMSO led, surprisingly, to a tertiary alcohol, presumably via ring opening of the expected intermediate epoxide. This is the first example of this type of ring opening in the presence of this base but the reaction time was longer than that normally employed in this process. Since the family members of the parent spiro[2.5]octanes are rare, an X-ray diffraction analysis was performed on 6-phenyl-1-oxa-6-phosphaspiro[2.5]octane 6-sulfide. This analysis revealed a space group of Pna21 with cell dimensions of: a=13.056(3) A, b=14.268(3) Å, and c=6.1522(11) Å. The phosphorinane ring assumes a slightly flattened chair conformation with the phenyl-P bond being equatorial and the P[dbnd]S bond being axial. The plane of the epoxide is virtually coincident with a pseudo-mirror plane through P(6), C(3), C(9) and S(15). The phenyl group is rotated out of this plane by 28.2°. Although the P—C distances (ring carbons) are 1.813(3) Å and 1.819(3) Å, respectively, and appear to be about normal, the P-phenyl bond of 1.813(3) Å is longer than in a few model systems. The C(3)—O(1) bond in the epoxide is axial or rather pseudo axial. Ring deformations are consistent with a few model epoxides the structures of which have been identified.
LIV.—A β-lactonic acid from acetone and malonic acid (1908)

A. N. Meldrum, J. Chem. Soc., Trans., 1908, 93, 598 DOI: 10.1039/CT9089300598
Homology‐dependent resistance: transgenic virus resistance in plants related to homology‐dependent gene silencing (1995)

Tobacco plants transformed with the RNA polymerase (RdRp) gene of potato virus X (PVX) that are extremely resistant to infection by potato virus X have previously been described. The PVX‐resistant plants accumulated the RdRp protein at a lower level than fully susceptible plants transformed with the same RdRp construct. In this paper the difference between the PVX‐resistant and susceptible transformed plants is investigated and it is demonstrated that there are three associated phenotypes of the RdRp transgene that vary in parallel between transformed lines. These phenotypes are: accumulation of the transgenic RdRp RNA at a low level; strain‐specific resistance to PVX; and the ability of the transgene to trans ‐inactivate homologous transgenes. This gene‐silencing potential of the transgenes conferring PVX resistance was illustrated by analysis of progeny from a cross between a transformant that was extremely resistant to PVX and a second PVX‐susceptible transformant. In other transformants, in which the resistance was less extreme, the same three phenotypes were associated but in a transgene dosage‐dependent manner. The same association of strain‐specific resistance and low‐level accumulation of the transgenic RdRp RNA was observed with plants that were transformed with mutant or wild‐type versions of the RdRp gene. Strain‐specific resistance was also produced in plants transformed with untranslatable versions of the RdRp transgene. Based on these data it is proposed that homology‐dependent gene silencing and transgenic resistance to PVX may be due to the same RNA‐based mechanism. An undefined genomic feature is proposed to account for the variation in the resistance and trans ‐inactivation phenotypes of different transformants. It is further proposed that this genome feature influences a cytoplasmic mechanism that degrades RNA with sequence homology to the silencing transgene.
Droplet-based microfluidic platform for heterogeneous enzymatic assays (2013)

Heterogeneous enzymatic reactions are used in many industrial processes including pulp and paper, food, and biofuel production. Industrially-relevant optimization of the enzymes used in these processes requires assaying them with insoluble substrates. However, platforms for high throughput heterogeneous assays do not exist thereby severely increasing the cost and time of enzyme optimization, or leading to the use of assays with soluble substrates for convenient, but non-ideal, optimization. We present an innovative approach to perform heterogeneous reactions in a high throughput fashion using droplet microfluidics. Droplets provide a facile platform for heterogeneous reactions as internal recirculation allows rapid mixing of insoluble substrates with soluble enzymes. Moreover, it is easy to generate hundreds or thousands of picoliter droplets in a small footprint chip allowing many parallel reactions. We validate our approach by screening combinations of cellulases with real-world insoluble substrates, and demonstrate that the chip-based screening is in excellent agreement with the conventional screening methods, while offering advantages of throughput, speed and lower reagent consumption. We believe that our approach, while demonstrated for a biofuel application, provides a generic platform for high throughput monitoring of heterogeneous reactions.
Ballistic Transport and Electrostatics in Metallic Carbon Nanotubes (2005)

We calculate the current and electrostatic potential drop in metallic carbon nanotube wires self-consistently by solving the Green's function and electrostatics equations in the ballistic case. About one-tenth of the applied voltage drops across the bulk of a nanowire, independent of the lengths considered here. The remaining nine-tenths of the bias drops near the contacts, thereby creating a nonlinear potential drop. The scaling of the electric field at the center of the nanotube with length (L) is faster than 1/L (roughly 1/L/sup 1.25-1.75/). At room temperature, the low bias conductance of larger-diameter nanotubes is larger than 4e/sup 2//h due to occupation of noncrossing subbands. The physics of conductance evolution with bias due to Zener tunneling in noncrossing subbands is discussed.
Aortic compliance in human hypertension. (1989)

Aortic compliance in normotensive and hypertensive Chinese subjects undergoing diagnostic cardiac catheterization was compared by using a newly described method that allows for determination of the pressure dependence of compliance if one assumes a value for the exponential coefficient of the pressure-volume relation of the large arteries. Under baseline conditions in the normotensive and hypertensive groups at mean aortic pressures of 96.3 and 128.6 mm Hg, aortic compliance averaged 1.47 and 0.80 ml/mm Hg, respectively. Compliance in the hypertensive group at a diastolic pressure of 99.4 mm Hg (which was nearly equal to the mean normotensive pressure) was 1.072 ml/mm Hg--still significantly lower than in the normotensive group. During nitroprusside infusion, however, the compliances in the hypertensive group increased to levels equal to or greater those in the normotensive group. Thus, these data confirm that aortic compliance is lower in hypertensive than in normotensive humans. They further demonstrate that the lower compliance cannot be attributed entirely to the elevated blood pressure, suggesting that excess smooth muscle tone may be partly responsible.