gebhart/patrepeval huggingface dataset:
Identification of Novel Smoothened Ligands Using Structure-Based Docking (2016)

The seven transmembrane protein Smoothened is required for Hedgehog signaling during embryonic development and adult tissue homeostasis. Inappropriate activation of the Hedgehog signalling pathway leads to cancers such as basal cell carcinoma and medulloblastoma, and Smoothened inhibitors are now available clinically to treat these diseases. However, resistance to these inhibitors rapidly develops thereby limiting their efficacy. The determination of Smoothened crystal structures enables structure-based discovery of new ligands with new chemotypes that will be critical to combat resistance. In this study, we docked 3.2 million available, lead-like molecules against Smoothened, looking for those with high physical complementarity to its structure; this represents the first such campaign against the class Frizzled G-protein coupled receptor family. Twenty-one high-ranking compounds were selected for experimental testing, and four, representing three different chemotypes, were identified to antagonize Smoothened with IC50 values better than 50 μM. A screen for analogs revealed another six molecules, with IC50 values in the low micromolar range. Importantly, one of the most active of the new antagonists continued to be efficacious at the D473H mutant of Smoothened, which confers clinical resistance to the antagonist vismodegib in cancer treatment.
Effects of Sho-saiko-to, San'o-shashin-to and Scutellariae Radix on Intracellular Ca2+ Mobilization in C6 Rat Glioma Cells. (1998)

Glial cells are able to support neurons physically and functionally. The present study was undertaken to determine the effects of Kampo medicines on glial cell function, especially Ca2+ mobilization. C6 rat glioma cells expressed H1-histamine, muscarinic cholinergic and adrenergic alpha1-receptors, stimulation of which resulted in phosphoinositide hydrolysis and increase in intracellular Ca2+ concentrations ([Ca2+]i). The water extracts of Sho-saiko-to and San'o-shashin-to, Kampo medicines which contain Scutellariae Radix (Ogon, the root of Scutellaria baicalensis GFORGI), inhibited histamine (100 microM)-induced increase in [Ca2+]i in a concentration-dependent manner. The water extract of Scutellariae Radix potently decreased [Ca2+]i in a concentration-dependent manner. Sho-saiko-to, San'o-shashin-to and Scutellariae Radix significantly inhibited histamine-induced accumulation of total [3H]inositol phosphates, consistent with their inhibition of the increase in [Ca2+1]i. These results suggest that Sho-saiko-to, San'o-shashin-to and Scutellariae Radix inhibit Ca2+ mobilization mediated via an inhibition of phospholipase C. The inhibitory effect may be important in interpreting the pharmacological actions of above Kampo medicines.
Surgical decompression for cerebral oedema in acute ischaemic stroke (2002)

There is no evidence from randomised-controlled trials to support the use of decompressive surgery for the treatment of cerebral oedema in acute ischaemic stroke. Evidence from randomised-controlled trials is needed to accurately assess the effect of decompressive surgery.
A successive-approximation-register ADC architecture for digital background calibration in high speed ADCs (2014)

In this paper, a digital background calibration scheme using an 8-b 10-MS/s successive approximation register (SAR) ADC to calibrate an 8-b 100-MS/s pipelined folding ADC is presented. In order to sample high frequency differential input signals, a new SAR ADC architecture based on the monotonic switching procedure is also proposed. Both ADCs are designed using a 0.18 µm CMOS technology. From the simulation results, it is shown that the SAR ERBW is around 400 MHz and the calibration scheme can reduce offset errors, gain mismatches, and memory effect in the high speed ADC. With Monte Carlo simulation, ENOB, SNDR, and SFDR of the pipelined folding ADC improve 1.75-b, 10.63 dB, and 7.9 dB on average, respectively.
Autocrine-Derived Epidermal Growth Factor Receptor Ligands Contribute to Recruitment of Tumor-Associated Macrophage and Growth of Basal Breast Cancer Cells In Vivo (2013)

Epidermal growth factor receptor (EGFR) expression has been linked to progression of basal breast cancers. Many breast cancer cells harbor the EGFR and produce its family of ligands, suggesting they may participate in autocrine and paracrine signaling with cells of the tumor microenvironment. EGFR ligand expression was profiled in the basal breast cancer cell line MDA-231 where AREG, TGF-alpha, and HBEGF were the three ligands most highly expressed. Autocrine signaling was modulated through silencing or overexpression of these three ligands using lentiviral constructs and the impact measured using motility, proliferation, and cytokine expression assays. Changes in receptor phosphorylation and receptor turnover were examined. Knockdown of AREG or TGF-alpha in vitro resulted in decreased motility (p < 0.05) and decreased expression of macrophage chemoattractants. Overexpression of TGF-alpha increased motility and chemoattractant expression, whereas AREG did not. HBEGF modulation had no effect on any cellular behaviors. All the cells with altered ligand production were inoculated into female athymic nude mice to form mammary fat pad tumors, followed by immunohistochemical analysis for necrosis, angiogenesis, and macrophage recruitment. In vivo, knockdown of AREG or TGF-alpha increased survival (p < 0.001) while decreasing angiogenesis (p < 0.001), tumor growth (p < 0.001), and macrophage attraction (p < 0.001). Overexpression of AREG appeared to elicit a greater effect than TGF-alpha on mammary fat pad tumor growth by increasing angiogenesis (p < 0.001) and macrophage attraction to the tumor (p < 0.01). We propose these changes in mammary tumor growth were the result of increased recruitment of macrophages to the tumor by cells with altered autocrine EGFR signaling. We conclude that AREG and TGF-alpha were somewhat interchangeable in their effects on EGFR signaling; however, TGF-alpha had a greater effect in vitro and AREG had a greater effect in vivo.
Degradation mechanism of spinel LiAl0.2Mn1.8O4 cathode materials on high temperature cycling (2001)

The structural degradation of the Al-doped spinel material, LiAl0.2Mn1.8O4, before and after charge–discharge cycling in the 4 V region at elevated temperature has been studied by X-ray diffraction and high-resolution transmission electron microscopy. The capacity loss during cycling was noticeably increased with cell operation temperature from 50 to 80 °C. The formation of tetragonal Li2Mn2O4 and the rocksalt phase Li2MnO3 in the spinel electrode cycled at elevated temperature could be responsible for the main cause of the capacity loss.
Training security officers to recognize the perils of weapons of mass destruction and pandemic flu contaminates. (2007)

In order to effectively manage disasters, hospital security operatives need to learn the ABC's of diagnosing exposure models, spotting exposed persons, and donning appropriate contaminate-controlling attire to limit potential exposure. This article spells out how the establishment of a WMD training program gives the Security Department the capability of helping to contain WMD exposures before they adversely impact the institutional setting. The department's "awesome" role in keeping hospitals free from contamination requires, according to the authors, dedicated, well trained, appropriately equipped, and highly motivated security officers who keep a watchful eye over the institutions they protect.
Multiple-Lane Vehicle Platooning based on a Multi-Agent Distributed Model Predictive Control Strategy (2018)

Vehicle platooning became an interesting topic in the last years, many researchers and practitioners from the academia and industry trying to develop new theories and design appropriate control methods and communication methodologies in order to bring this concept as fast as possible on the roads. Since vehicles drive on multi-lane roads and highways, the subsequent paradigm was to treat vehicles as swarms, i.e., groups of vehicles that travel closely together on different lanes and are electronically connected. A step forward towards this new concept would be the design of multiple-lane platoons. As such, this paper proposes a multi-agent distributed model predictive control strategy for the longitudinal coordination of the vehicles in individual platoons and a classical PI control algorithm for the lateral control of each vehicle in the platoon w.r.t. its neighbors. The simulation results obtained in Matlab/Simulink and the performance analysis prove that the concept is viable.
Feedback-Induced Temporal Control of “Breathing” Polymersomes To Create Self-Adaptive Nanoreactors (2018)

Here we present the development of self-regulated "breathing" polymersome nanoreactors that show temporally programmable biocatalysis induced by a chemical fuel. pH-sensitive polymersomes loaded with horseradish peroxidase (HRP) and urease were developed. Addition of an acidic urea solution ("fuel") endowed the polymersomes with a transient size increase and permeability enhancement, driving a temporal "ON" state of the HRP enzymatic catalysis; subsequent depletion of fuel led to shrinking of the polymersomes, resulting in the catalytic "OFF" state. Moreover, the nonequilibrium nanoreactors could be reinitiated several cycles as long as fuel was supplied. This feedback-induced temporal control of catalytic activity in polymersome nanoreactors provides a platform for functional nonequilibrium systems as well as for artificial organelles with precisely controlled adaptivity.
Thermoelectric power in carbon nanotubes and quantum wires of nonlinear optical, optoelectronic, and related materials under strong magnetic field: Simplified theory and relative comparison (2008)

We study thermoelectric power under strong magnetic field (TPM) in carbon nanotubes (CNTs) and quantum wires (QWs) of nonlinear optical, optoelectronic, and related materials. The corresponding results for QWs of III-V, ternary, and quaternary compounds form a special case of our generalized analysis. The TPM has also been investigated in QWs of II-VI, IV-VI, stressed materials, n-GaP, p-PtSb2, n-GaSb, and bismuth on the basis of the appropriate carrier dispersion laws in the respective cases. It has been found, taking QWs of n-CdGeAs2, n-Cd3As2, n-InAs, n-InSb, n-GaAs, n-Hg1−xCdxTe, n-In1−xGaxAsyP1−y lattice-matched to InP, p-CdS, n-PbTe, n-PbSnTe, n-Pb1−xSnxSe, stressed n-InSb, n-GaP, p-PtSb2, n-GaSb, and bismuth as examples, that the respective TPM in the QWs of the aforementioned materials exhibits increasing quantum steps with the decreasing electron statistics with different numerical values, and the nature of the variations are totally band-structure-dependent. In CNTs, the TPM exhibits periodic oscillations with decreasing amplitudes for increasing electron statistics, and its nature is radically different as compared with the corresponding TPM of QWs since they depend exclusively on the respective band structures emphasizing the different signatures of the two entirely different one-dimensional nanostructured systems in various cases. The well-known expression of the TPM for wide gap materials has been obtained as a special case under certain limiting conditions, and this compatibility is an indirect test for our generalized formalism. In addition, we have suggested the experimental methods of determining the Einstein relation for the diffusivity-mobility ratio and the carrier contribution to the elastic constants for materials having arbitrary dispersion laws.
Synthesis, modification and structural binding of heat-shock proteins in tomato cell cultures (1984)

Synthesis of about 30 acidic and 18 basic heat-shock proteins (hsps) is induced in suspension cultures of tomato (Lycopersicon peruvianum) if subjected to supraoptimal temperature conditions (35-40 degrees C). A characteristic aspect of the plant heat-shock response is the formation of cytoplasmic granular aggregates, heat-shock granules, containing distinct heat-shock proteins as major structural components and, in addition, several hitherto undetected minor acidic and basic heat-shock proteins. Structural binding of heat-shock proteins, i.e. assembly of heat-shock granules, is dependent on the persistance of supraoptimal temperature conditions. Despite the ongoing synthesis also at 25 degrees C, e.g. in pulse heat-shocked cultures, these proteins are accumulated exclusively in soluble form. Individual heat-shock proteins are characterized by their kinetics of synthesis and are classified by their compartmentation behaviour into class A proteins (exclusively found in soluble form, e.g. hsps 95 and 80), class B proteins (5-10% bound to heat-shock granules, e.g. hsps 70, 68), class C proteins (30-80% bound to heat-shock granules, e.g. hsps 21, 17, 15) and class D proteins, which are minor heat-shock proteins only detected in structure-bound form. Major representatives are modified proteins, i.e. hsps 95, 80, 70 and 68 are phosphorylated and hsps 80, 74, 70 and 17 are methylated proteins (numbers 70, 80 etc. refer to 10(-3) Mr). Under heat-shock conditions synthesis of the proteins detected in control cells (25 degrees C proteins) exhibits two patterns. There are proteins with continued and proteins with discontinued synthesis. Synthesis of most of the latter proteins is resumed very rapidly after shift-down to 25 degrees C, even in the presence of actinomycin D. We conclude that reversible segregation of distinct mRNA species from the translation apparatus contributes to the heat-shock-specific pattern of protein synthesis in plants also.
A Facile One‐Step Synthesis of a Lipophilic Gold(<scp>I</scp>) Carbene Complex –X‐ray Crystal Structures of LAuCl and LAuC≡CH (L = 1,3‐di‐<i>tert‐</i>Butylimidazol‐2‐ylidene) (2005)

Abstract The reaction of Au(CO)Cl with 1,3‐di‐ tert ‐butylimidazol‐2‐ylidene and 1,3‐dimesitylimidazol‐2‐ylidene in toluene at room temperature results in CO evolution and readily affords in high yield the adducts 1a and 1b , respectively. The reaction of 1a and 1b with ethynylmagnesium chloride in THF yields 2a and 2b , respectively. The crystal structures of 1a , 1b , and 2a were determined. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Interfacial Charge Carrier Dynamics of the Three-Component In<sub>2</sub>O<sub>3</sub>–TiO<sub>2</sub>–Pt Heterojunction System (2012)

The interfacial charge carrier dynamics of the three-component semiconductor–semiconductor–metal heterojunction system were investigated and presented for the first time. The samples were prepared by selectively depositing Pt nanoparticles on the TiO2 surface of In2O3-decorated TiO2 nanobelts (In2O3–TiO2 nanobelts (NBs)) using the typical photodeposition method. For In2O3–TiO2 NBs, because of the difference in band structures between In2O3 and TiO2, the photoexcited electrons of In2O3 nanocrystals would preferentially transfer to TiO2 NBs to cause charge carrier separation. With the introduction of Pt on TiO2 surface, a fluent electron transfer from In2O3, through TiO2, and eventually to Pt was achieved, giving rise to the increasingly pronounced charge separation property for the as-prepared In2O3–TiO2–Pt NBs. The remarkable charge separation of the samples was revealed with the corresponding photocurrent measurements. Time-resolved photoluminescence spectra were measured to quantitatively analyze the electron transfer event between In2O3 and TiO2 for In2O3–TiO2 NBs and its dependence on Pt deposition. Upon the deposition of Pt, In2O3–TiO2 NBs showed an increased apparent electron-scavenging rate constant, fundamentally consistent with the result of their performance evaluation in photocatalysis. The current study provides a new paradigm for designing highly efficient three-component nanoheterojunction photocatalysts which can effectively produce chemical energy from absorbing light.
Increased Survival and Function of SOD1 Mice After Glial Cell-Derived Neurotrophic Factor Gene Therapy (2002)

Amyotrophic lateral sclerosis (ALS) is caused by a progressive degeneration of motor neurons. The cause of sporadic ALS is not known, but 1-2% of all cases are familial and caused by mutations in the copper-zinc superoxide dismutase (SOD1) gene. Transgenic SOD1 mice serve as a transgenic mouse model for these cases. Glial cell-derived neurotrophic factor (GDNF) has a potent trophic effect on motor neurons. Clinical trials in which growth factors have been systemically administered to ALS patients have not been effective, owing in part to the short half-life of these factors and their low concentrations at target sites. Gene transfer of therapeutic factors to motor neurons and/or their target cells, such as muscle, may overcome these problems. Previously, we and others have shown that intramuscularly administered adenovirus vector (AVR) results in foreign gene expression not only in muscle cells, but also in relevant motor neurons in the spinal cord, because of retrograde axonal transport. In this study we utilized an AVR to introduce GDNF into muscles of neonatal SOD1 mice. We showed that AVR-mediated GDNF expression delayed the onset of disease by 7 +/- 8 days (mean +/- SD), prolonged survival by 17 +/- 10 days, and delayed the decline in motor functions (as determined on a rotating rod) by 7-14 days. These results demonstrate that gene delivery to muscle and motor neurons has the potential to treat devastating neurodegenerative diseases such as ALS.
The Functional Application of the Propeller Load Curve for Fixed Pitch Propellers (2006)

This thesis attempts to help the flight test community by using the propeller load curve (also known as prop load) to find brake horsepower (BHP) easily with only a propeller tachometer. This thesis also covers the equation for the propeller load curve. The flight test was done using a Piper Cherokee 180 equipped with a Lycoming 0-360-A3A engine. The flight test data were collected at University of Tennessee Space Institute (UTSI). This data were then compared to the prop load from the engine manufacturer. Based on the result of this flight test, using the prop load equation from the Lycoming will result in BHP that is within 96% agreement to the flight test BHP. The result of the test will also show that the equation for the propeller load curve at sea level is HP = K × (RPM3) where K = constant (Aircraft 1949). This thesis will also prove that if you are not at sea level, the equation then becomes HP = (√σ × K × RPM3) where σ = the atmospheric density ratio. Recommendations include additional tests with multiple engines on a test stand.
Investigation of the effects of an airfoil section modification on the aerodynamic characteristics at subsonic and supersonic speeds of a thin swept wing of aspect ratio 3 in combination with a body (1955)

Memorandum presenting a wind tunnel investigation to determine the effects of an airfoil section modification consisting of a greatly increased leading-edge radius and slight forward camber on the aerodynamic characteristics of a thin swept-wing-body combination at Mach numbers from 0.06 to 1.9. The tests showed that full-span modification of the wing resulted in very marked improvement in stability, drag, and high-lift characteristics for the configuration at low speeds due to the maintenance of attached flow over the wing to high lift coefficients.
Gross feature recognition of Anatomical Images based on Atlas grid (GAIA): Incorporating the local discrepancy between an atlas and a target image to capture the features of anatomic brain MRI (2013)

We aimed to develop a new method to convert T1-weighted brain MRIs to feature vectors, which could be used for content-based image retrieval (CBIR). To overcome the wide range of anatomical variability in clinical cases and the inconsistency of imaging protocols, we introduced the Gross feature recognition of Anatomical Images based on Atlas grid (GAIA), in which the local intensity alteration, caused by pathological (e.g., ischemia) or physiological (development and aging) intensity changes, as well as by atlas-image misregistration, is used to capture the anatomical features of target images. As a proof-of-concept, the GAIA was applied for pattern recognition of the neuroanatomical features of multiple stages of Alzheimer's disease, Huntington's disease, spinocerebellar ataxia type 6, and four subtypes of primary progressive aphasia. For each of these diseases, feature vectors based on a training dataset were applied to a test dataset to evaluate the accuracy of pattern recognition. The feature vectors extracted from the training dataset agreed well with the known pathological hallmarks of the selected neurodegenerative diseases. Overall, discriminant scores of the test images accurately categorized these test images to the correct disease categories. Images without typical disease-related anatomical features were misclassified. The proposed method is a promising method for image feature extraction based on disease-related anatomical features, which should enable users to submit a patient image and search past clinical cases with similar anatomical phenotypes.
Efficient Cleavage of DNA by Iron(III) Triazacyclononane Derivatives (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEfficient Cleavage of DNA by Iron(III) Triazacyclononane DerivativesGail C. Silver and William C. TroglerCite this: J. Am. Chem. Soc. 1995, 117, 14, 3983–3993Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://pubs.acs.org/doi/10.1021/ja00119a013https://doi.org/10.1021/ja00119a013research-articleACS PublicationsRequest reuse permissionsArticle Views389Altmetric-Citations49LEARN 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 (2)»Supporting Information Supporting Information Get e-Alerts