gebhart/patrepeval huggingface dataset:
Evolving Therapeutic Indications for N-Type Calcium Channel Blockers: From Chronic Pain to Alcohol Abuse (2010)

Clinical exploitation of the therapeutic potential of calcium channels has long been limited to L-type blockers for cardiovascular diseases. Recently, N-type blockers have been fully validated for the treatment of chronic pain, following approval of the intrathecally active ziconotide (Prialt(®)). This review describes the successful efforts to broaden the therapeutic scope of this mechanism to other major CNS indications, based on the discovery of N-type blockers orally active against pain. In animal models, the N-type blocker and pain-reducing NP078585 is efficacious against key elements of ethanol dependency, including self-administration and relapse. NP078585 moderately stimulates brain dopamine release without inducing reward or hyperlocomotion. N-type blockers may emerge as a novel class of 'dopamine stabilizers' for the treatment of drug dependency and other neuropsychiatric disorders without the side effects of current therapies.
Strong broadband intensity noise squeezing from near-infrared to terahertz frequencies in semiconductor lasers with nonlinear dissipation (2022)

The generation and application of squeezed light have long been central goals of quantum optics, enabling sensing below the standard quantum limit, optical quantum computing platforms, and more. Intensity noise squeezing of bright (coherent) states, in contrast to squeezed vacuum, is relatively underdeveloped. Bright squeezing has been generated directly through nonlinear optical processes or ``quietly pumped'' semiconductor lasers. However, these methods suffer from weak squeezing limits, narrow operating wavelength ranges, and have not been explored at large bandwidths. Here, we show how semiconductor lasers with sharp intensity-dependent dissipation can support highly broadband intensity noise squeezing from infrared (IR) to terahertz (THz) wavelengths, the latter of which has remained unexplored in quantum noise studies. Our protocol realizes strongly ($&gt;10$ dB) intensity noise-squeezed intracavity quantum states, which could create a new regime for cavity quantum electrodynamics experiments, as well as strong output squeezing surpassing gigahertz bandwidths. Furthermore, we show how the same systems also create self-pulsing and bistable mean field behavior, enabling control of light in both the temporal and noise domains. The existence of these multiple functionalities in both the classical and quantum mechanical domains in a single semiconductor laser platform, from IR to THz wavelengths, could enable advances in on-chip quantum optical communication, computing, and sensing across the electromagnetic spectrum.
Improvement and commissioning of a novel technology for the measurement of laser-beam profiles (2007)

Measurement of the laser beam propagation factor M<sup>2</sup> is essential in many laser applications including materials processing, laser therapy, and lithography. In this paper we describe the characterisation of a prototype device using a cross-distorted diffraction grating known as an Image Multiplex (IMP<sup>(R)</sup>) grating, to measure the M<sup>2</sup> value of laser beams. The advantage of the IMP<sup>(R)</sup> grating instrument lies in its ability to simultaneously image nine positions along the beam path. This enables beam propagation parameters to be calculated both for pulsed lasers and lasers with rapidly changing propagation characteristics. This is in contrast to the scanned technique recommended by the ISO, which is relatively slow and in practice can only be easily used with cw sources. The characterisation was accomplished by comparison of results from the IMP<sup>(R)</sup> grating device with those obtained using the accepted methodology described in the ISO 11146 series of standards through measurements conducted by the National Physical Laboratory. The scope of the work also included provision of a traceability route to international standards, and an uncertainty budget, to allow the intended user community to have confidence in measurements obtained when using the device, and to enable them to use it as part of their quality framework.
Simulation of Ion Transport through Percolated Aggregates in Precise Sulfophenylated Polyethylene Ionomers (2020)

Abstract not provided.
Invasion of Epithelial Cells by Locus of Enterocyte Effacement-Negative EnterohemorrhagicEscherichia coli (2005)

The majority of enterohemorrhagic Escherichia coli (EHEC) strains associated with severe disease carry the locus of enterocyte effacement (LEE) pathogenicity island, which encodes the ability to induce attaching and effacing lesions on the host intestinal mucosa. While LEE is essential for colonization of the host in these pathogens, strains of EHEC that do not carry LEE are regularly isolated from patients with severe disease, although little is known about the way these organisms interact with the host epithelium. In this study, we compared the adherence properties of clinical isolates of LEE-negative EHEC with those of LEE-positive EHEC O157:H7. Transmission electron microscopy revealed that LEE-negative EHEC O113:H21 was internalized by Chinese hamster ovary (CHO-K1) epithelial cells and that intracellular bacteria were located within a membrane-bound vacuole. In contrast, EHEC O157:H7 remained extracellular and intimately attached to the epithelial cell surface. Quantitative gentamicin protection assays confirmed that EHEC O113:H21 was invasive and also showed that several other serogroups of LEE-negative EHEC were internalized by CHO-K1 cells. Invasion by EHEC O113:H21 was significantly reduced in the presence of the cytoskeletal inhibitors cytochalasin D and colchicine and the pan-Rho GTPase inhibitor compactin, whereas the tyrosine kinase inhibitor genistein had no significant impact on bacterial invasion. In addition, we found that EHEC O113:H21 was invasive for the human colonic cell lines HCT-8 and Caco-2. Overall these studies suggest that isolates of LEE-negative EHEC may employ a mechanism of host cell invasion to colonize the intestinal mucosa.
How Complex Is Cancer Intracellular Signaling Space in FIB-SEM Images? (2012)

How cell regulates its intracellular features to optimize their signaling pathways is still far from understanding. Recent advancement in microscopy imaging of the structure of cell organelles enables biomedical researchers to study cell morphology in great detail to discover the pathogeneses of diseases by information obtained at molecular level. A particular interest is to quantify the complexity of the spatial content of the intracellular space captured by the combination of focused ion beam (FIB) and scanning electron microscope (SEM) imaging systems. Such quantitative measure of the complexity of organelles is expected to be a useful tool for benchmarking biological simulations of cancers and controlling disease-specific drug effects. In this paper, for the first time nonlinear dynamical models are utilized to investigate the structural characteristics of intracellular space using FIB-SEM technology to quantify the complex architecture of cell organelles.
Human H7N9 and H5N1 Influenza Viruses Differ in Induction of Cytokines and Tissue Tropism (2014)

The novel avian-origin H7N9 pandemic represents a serious threat to public health. The ability of H7N9 to cause serious lung pathology, leading in some cases to the development of acute respiratory distress syndrome, is of particular concern. Initial reports of H7N9 infection compared them to infections caused by highly pathogenic avian (HPAI) H5N1 viruses. Thus, it is of critical importance to understand the pathology and immunological response to infection with H7N9 compared to HPAI H5N1 viruses. We compared these responses in both in vitro and in vivo models, and found that H5N1 and H7N9 infections exhibit distinct pathological, immunological, and tissue tropism differences that could explain differences in clinical disease and viral transmission.
Feature analysis for automatic detection of pathological speech (2003)

This study focuses on a robust, rapid and accurate system for automatic detection of normal and pathological speech. This system employs noninvasive, non-expensive and fully automated measures of vocal tract characteristics and excitation information. Mel-frequency filterbank cepstral coefficients and measures of pitch dynamics were modeled by Gaussian mixtures in a hidden Markov model (HMM) classifier. The method was evaluated using the sustained phoneme /a/ data obtained from over 700 subjects of normal and different pathological cases from the Massachusetts Eye and Ear Infirmary (MEEI) database. This method attained 99.44% correct classification rates for discrimination of normal and pathological speech for sustained /a/. This represents 8% detection error rate improvement over the best performing classifier using carefully measured features prevalent in the state-of-the-art in pathological speech analysis.
Pharmacologically blocking p53-dependent apoptosis protects intestinal stem cells and mice from radiation (2015)

Exposure to high levels of ionizing radiation (IR) leads to debilitating and dose-limiting gastrointestinal (GI) toxicity. Using three-dimensional mouse crypt culture, we demonstrated that p53 target PUMA mediates radiation-induced apoptosis via a cell-intrinsic mechanism, and identified the GSK-3 inhibitor CHIR99021 as a potent radioprotector. CHIR99021 treatment improved Lgr5+ cell survival and crypt regeneration after radiation in culture and mice. CHIR99021 treatment specifically blocked apoptosis and PUMA induction and K120 acetylation of p53 mediated by acetyl-transferase Tip60, while it had no effect on p53 stabilization, phosphorylation or p21 induction. CHIR99021 also protected human intestinal cultures from radiation by PUMA but not p21 suppression. These results demonstrate that p53 posttranslational modifications play a key role in the pathological and apoptotic response of the intestinal stem cells to radiation and can be targeted pharmacologically.
Inherently Safe Resonant Reset Forward Converter Using a Bias-Enhanced SiC JFET (2006)

The power junction field effect transistor (JFET) is the second most mature SiC device, after the SiC Schottky diode, and is commonly associated with normally on functionality; but this feature is often viewed problematically for off-line dc-to-dc converter applications. Two inherently safe, single-switch dc-dc converter designs have been developed that put into practice pure SiC JFET devices (i.e., without cascoded devices) that possess enhancement-mode functionality and bias-enhanced blocking. These ‘Quasi-Off’ devices are designed to block half of the rated blocking voltage at zero gate bias and achieve full rated blocking voltage with a modest negative bias, typically between 0 and -5 V. Inherent safety is provided by utilizing the enhancement mode functionality of these devices as well as appropriate gate driver design. Bias enhanced blocking matches the dynamic stress encountered by modern high-frequency power supply topologies to the ratings of the device while recognizing that the larger dynamic stress is typically encountered only when the power supply (and especially the gate driver) is functioning properly.
Measurement of the cross-section ratio σ(χc2)/σ(χc1) for prompt χc production at s=7 TeV (2012)

The prompt production of the charmonium χc1 and χc2 mesons has been studied in proton–proton collisions at the Large Hadron Collider at a centre-of-mass energy of s=7 TeV. The χc mesons are identified through their decays χc→J/ψγ with J/ψ→μ+μ− using 36 pb−1 of data collected by the LHCb detector in 2010. The ratio of the prompt production cross-sections for the two χc spin states, σ(χc2)/σ(χc1), has been determined as a function of the J/ψ transverse momentum, pTJ/ψ, in the range from 2 to 15 GeV/c. The results are in agreement with the next-to-leading order non-relativistic QCD model at high pTJ/ψ and lie consistently above the pure leading-order colour-singlet prediction.
The Effects of Hyperosmolar Solutions on (1983)

Hyperosmotic sucrose solutions elicited tension from rat aortic strips in direct proportion to osmolarity. Norepinephrine-induced tension was reduced in proportion to increases in osmolarity; however, reduction of barium-induced tension by hyperosmolar solutions was minimal. Norepinephrine-induced tension is primarily dependent on intracellular calcium mobilization, while barium-induced tension is primarily dependent on extracellular calcium influx. Therefore, hyperosmolar solutions may alter vasoconstriction associated with intracellular calcium mobilization rather than that associated with extracellular calcium influx. In the presence of verapamil which blocks calcium entry into muscle, barium-induced tension was eliminated while the direct tension elicited by hyperosmolar solutions was slightly affected (6% reduction) and the inhibitory effect of hyperosmolar solutions on norepinephrine-induced tension was still observed. In contrast, the tension elicited by hyperosmolar solutions was greatly reduced by papaverine which promotes sequestration of myoplasmic calcium to cause relaxation. The vascular effects of hyperosmolar solutions may be due to alterations in the intracellular calcium rather than the extracellular calcium utilized by vasoconstricting agents.
Imidazopyridine‐Based Inhibitors of Glycogen Synthase Kinase 3: Synthesis and Evaluation of Amide Isostere Replacements of the Carboxamide Scaffold (2012)

In this study, we explored the effect of bioisostere replacement in a series of glycogen synthase kinase 3 (GSK3) inhibitors based on the imidazopyridine core. The synthesis and biological evaluation of a number of novel sulfonamide, 1,2,4-oxadiazole, and thiazole derivates as amide bioisosteres, as well as a computational rationalization of the obtained results are reported.
Processeur vidéo programmable pour la téléphonie mobile eISP, une architecture de calcul très basse consommation à faible empreinte silicium pour le traitement vidéo HD (2010)

CMOS sensors are more and more integrated in consumer products. The images issued from these sensors need to be digitally processed before being displayed. Today, CMOS sensors are associated to dedicated components, thus maintaining the power consumption to a low level. On the opposite side, the use of dedicated components limits the flexibility of the hardware and prevents the development of platforms able to run newer image processing algorithms. This paper describes eISP, a programmable architecture which presents a computational efficiency, a silicon area and a power consumption suitable for the processing of 1080p HD images inside of a mobile phone.
First Measurement of theCP-Violating Phase inBs0→ϕϕDecays (2013)

A first flavor-tagged measurement of the time-dependent CP-violating asymmetry in B(s)(0) → ϕϕ decays is presented. In this decay channel, the CP-violating weak phase arises due to CP violation in the interference between B(s)(0)-B(s)(0) mixing and the b → sss gluonic penguin decay amplitude. Using a sample of pp collision data corresponding to an integrated luminosity of 1.0 fb(-1) and collected at a center-of-mass energy of 7 TeV with the LHCb detector, 880 B(s)(0) → ϕϕ signal decays are obtained. The CP-violating phase is measured to be in the interval [-2.46,-0.76] rad at a 68% confidence level. The p value of the standard model prediction is 16%.
An Efficient Fpga Based Mimo-Mmse Detector (2007)

Publication in the conference proceedings of EUSIPCO, Poznan, Poland, 2007
Characterization of electronic displays using CMOS single‐photon avalanche diode image sensors (2018)

Abstract Advanced complementary metal‐oxide semiconductor‐compatible single‐photon avalanche diode array technology is progressing rapidly and is being deployed in a wide range of applications. We report for the first time the use of a complementary metal‐oxide semiconductor‐compatible single‐photon avalanche diode array to perform detailed optical measurements on pixels of an organic light‐emitting diode microdisplay at very high sampling rate, very low light level, and over a very wide dynamic range of luminance. This offers a clear demonstration of the huge potential of this single‐photon avalanche diode technology to reveal hitherto obscure details of the optical characteristics of individual and groups of organic light‐emitting diode pixels.
Social Simulacra: Creating Populated Prototypes for Social Computing Systems (2022)

Social computing prototypes probe the social behaviors that may arise in an envisioned system design. This prototyping practice is currently limited to recruiting small groups of people. Unfortunately, many challenges do not arise until a system is populated at a larger scale. Can a designer understand how a social system might behave when populated, and make adjustments to the design before the system falls prey to such challenges? We introduce social simulacra, a prototyping technique that generates a breadth of realistic social interactions that may emerge when a social computing system is populated. Social simulacra take as input the designer's description of a community's design -- goal, rules, and member personas -- and produce as output an instance of that design with simulated behavior, including posts, replies, and anti-social behaviors. We demonstrate that social simulacra shift the behaviors that they generate appropriately in response to design changes, and that they enable exploration of "what if?" scenarios where community members or moderators intervene. To power social simulacra, we contribute techniques for prompting a large language model to generate thousands of distinct community members and their social interactions with each other; these techniques are enabled by the observation that large language models' training data already includes a wide variety of positive and negative behavior on social media platforms. In evaluations, we show that participants are often unable to distinguish social simulacra from actual community behavior and that social computing designers successfully refine their social computing designs when using social simulacra.
Abstract 060: POLDIP-2/NOX-4 Generates Hydrogen Peroxide that Impairs Myogenic Response of Afferent Arterioles from Mice with the Reduced Renal Mass Model of Chronic Kidney Disease (2015)

Background: Because we have found that myogenic contractions are stimulated by superoxide (O 2 .- ) but inhibited by hydrogen peroxide (H 2 O 2 ), we tested the hypothesis that H 2 O 2 is the cause of the impaired myogenic responses of afferent arterioles from mice with the reduced renal mass (RRM) model of chronic kidney disease (CKD). Methods: Mice were subjected to 5/6 surgical nephrectomy or sham operations and fed 6% salt for 3 months. Single afferent arterioles were perfused, their diameter measured directly and O 2 .- and H 2 O 2 measured by fluorescence microscopy. Results: The perfusion pressure of isolated afferent arterioles was increased from 40 to 80 mmHg to study myogenic responses. Arterioles from mice with RRM (vs sham) had a greater increase in O 2 .- (21.2 ± 1.9 versus 11.3 ± 2.5%; p &lt; 0.01) and especially H 2 O 2 (28.7 ± 3.7 versus 4.2 ± 0.4%, P&lt;0.005), but a reduction in myogenic contraction (-1.7 ± 4.3 versus -14.4 ± 3.6%; p &lt; 0.005) . Myogenic contractions were paradoxically reversed in afferent arterioles from mice with RRM after reduction in O 2 .- by PEG-SOD (+3.3 ± 1.5 versus -1.7 ± 4.3%, P&lt;0.05) or deletion of p47 phox (+2.5 ± 1.4 versus -1.7 ± 4.3%, P&lt;0.05). In contrast, myogenic responses were increased even above the levels of shams in arterioles from mice with RRM after reduction in H 2 O 2 by PEG-catalase (-19.1 ± 1.6 versus -1.7 ± 4.3%, P&lt;0.005) or transgenic overexpression of catalase in smooth muscle cells (-10.7 ± 1.3 versus -1.7 ± 4.3%, P&lt;0.01). Gene expression for NOX-4 and POLDIP-2 (main source of H 2 O 2 ) was increased 40-50% (P&lt;0.05) in individual afferent arterioles from mice with RRM. Moreover, the myogenic contractions in the arterioles from POLDIP-2+/- mice with RRM were similar to POLDIP-2+/- with sham operations (-7.7 ± 0.9 versus -8.0 ± 0.6, P=NS). Conclusions: Afferent arterioles from mice with RRM had severely impaired myogenic responses that were attributed to increased H 2 O 2 generation from POLDIP-2/NOX-4 that may therefore be novel targets to maintain autoregulation and protect kidneys from barotrauma in CKD.
Expression of CXCR3 on Adaptive and Innate Immune Cells Contributes Oviduct Pathology throughout Chlamydia muridarum Infection. (2017)

CXCR3 is a chemokine receptor expressed on a wide range of leukocytes, and it is involved in leukocyte migration throughout the blood and lymphatics. Specifically, CXCR3 is required for lymphocyte homing to the genital mucosa. When compared to wild type (WT) mice, CXCR3 deficiency (CXCR3-/-) mice infected with <i>Chlamydia muridarum (C. muridarum)</i> did not display impaired clearance and resolution of infection. However, they possessed significantly higher bacterial burden and lower levels of IFN-γ-producing TH1 cells. The knockouts also demonstrated a significant decrease in the level of activated conventional dendritic cells in the GT, ultimately leading to the decrease in activated TH1 cells. In addition, few activated plasmacytoid dendritic cells, which possess an inflammatory phenotype, were found in the lymph node of infected mice. This reduction in pDCs may be responsible for the decrease in neutrophils, which are acute inflammatory cells, in the CXCR3-/- mice. Due to the significantly reduced level of acute inflammation, these mice also possess a decrease in dilation and pathology in the oviduct. This demonstrates that the CXCR3-/- mice possess the ability to clear <i>C. muridarum</i> infections, but they do so without the increased inflammation and pathology in the GT.
The quantitation of long‐chain acyl‐CoA in mammalian tissue (1992)

Intracellular long-chain acyl-CoA esters are key metabolites in lipid metabolism. A rapid procedure was developed for the isolation of long-chain acyl-CoA from mammalian tissues. Acyl-CoA was extracted from the tissue with chloroform/methanol and separated from other lipid-containing metabolites by phase partition with solvents. The content and the molecular species of acyl-CoA were determined by gas-liquid chromatography. In rat liver and hamster heart, the total acyl-CoA content was estimated to be 83 +/- 11 and 61 +/- 9 nmol/g wet weight, respectively. The results obtained are comparable to those reported in previous studies. The relative ease of this procedure would permit the determination of acyl-CoA contents in a large number of samples.
Cadmium sulfide/copper sulfide heterojunction cell research. Volume I. Final report, September 1, 1979-March 15, 1982 (1983)

Thin-film Cu/sub 2/S/(CdZn)S solar cells have been made with a conversion efficiency of over 10% in actual sunlight testing. A reliable laboratory scale procedure has been developed for producing cells of this type. A technique has been developed for laser scanning ungridded cell material to locate the defects responsible for electrolytic decomposition of the Cu/sub 2/S and the associated loss in cell output. Improved production procedures were developed to reduce by orders of magnitude the number of such defects. Remaining defects have been neutralized using a laser pulse technique. Defect-free Cu/sub 2/S/CdS material has been shown to be stable under continuous illumination at open-circuit voltage for periods in excess of 500 hours. A procedure for depositing compound semiconductors such as (CdZn)S has been developed utilizing temperature controlled elemental sources. The technique has also been applied to CuInSe/sub 2/.