gebhart/patrepeval huggingface dataset:
Selectively targeting an inactive conformation of interleukin-2-inducible T-cell kinase by allosteric inhibitors (2014)

ITK (interleukin-2-inducible T-cell kinase) is a critical component of signal transduction in T-cells and has a well-validated role in their proliferation, cytokine release and chemotaxis. ITK is an attractive target for the treatment of T-cell-mediated inflammatory diseases. In the present study we describe the discovery of kinase inhibitors that preferentially bind to an allosteric pocket of ITK. The novel ITK allosteric site was characterized by NMR, surface plasmon resonance, isothermal titration calorimetry, enzymology and X-ray crystallography. Initial screening hits bound to both the allosteric pocket and the ATP site. Successful lead optimization was achieved by improving the contribution of the allosteric component to the overall inhibition. NMR competition experiments demonstrated that the dual-site binders showed higher affinity for the allosteric site compared with the ATP site. Moreover, an optimized inhibitor displayed non-competitive inhibition with respect to ATP as shown by steady-state enzyme kinetics. The activity of the isolated kinase domain and auto-activation of the full-length enzyme were inhibited with similar potency. However, inhibition of the activated full-length enzyme was weaker, presumably because the allosteric site is altered when ITK becomes activated. An optimized lead showed exquisite kinome selectivity and is efficacious in human whole blood and proximal cell-based assays.
Inhibition of Focal Adhesion Kinase Signaling by Integrin α6β1 Supports Human Pluripotent Stem Cell Self-Renewal (2016)

Self-renewal of human embryonic stem cells and human induced pluripotent stem cells (hiPSCs)-known as pluripotent stem cells (PSC)-is influenced by culture conditions, including the substrate on which they are grown. However, details of the molecular mechanisms interconnecting the substrate and self-renewal of these cells remain unclear. We describe a signaling pathway in hPSCs linking self-renewal and expression of pluripotency transcription factors to integrin α6β1 and inactivation of focal adhesion kinase (FAK). Disruption of this pathway results in hPSC differentiation. In hPSCs, α6β1 is the dominant integrin and FAK is not phosphorylated at Y397, and thus, it is inactive. During differentiation, integrin α6 levels diminish and Y397 FAK is phosphorylated and activated. During reprogramming of fibroblasts into iPSCs, integrin α6 is upregulated and FAK is inactivated. Knockdown of integrin α6 and activation of β1 integrin lead to FAK phosphorylation and reduction of Nanog, Oct4, and Sox2, suggesting that integrin α6 functions in inactivation of integrin β1 and FAK signaling and prevention of hPSC differentiation. The N-terminal domain of FAK, where Y397 is localized, is in the nuclei of hPSCs interacting with Oct4 and Sox2, and this immunolocalization is regulated by Oct4. hPSCs remodel the extracellular microenvironment and deposit laminin α5, the primary ligand of integrin α6β1. Knockdown of laminin α5 resulted in reduction of integrin α6 expression, phosphorylation of FAK and decreased Oct4. In conclusion, hPSCs promote the expression of integrin α6β1, and nuclear localization and inactivation of FAK to supports stem cell self-renewal. Stem Cells 2016;34:1753-1764.
Dimers, trimers, and tetramers of cytosine with guanine (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDimers, trimers, and tetramers of cytosine with guanineNidhi Gupta Williams, Loren Dean Williams, and Barbara Ramsay ShawCite this: J. Am. Chem. Soc. 1989, 111, 18, 7205–7209Publication Date (Print):August 1, 1989Publication History Published online1 May 2002Published inissue 1 August 1989https://doi.org/10.1021/ja00200a046RIGHTS & PERMISSIONSArticle Views270Altmetric-Citations50LEARN 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 InReddit PDF (600 KB) Get e-Alerts Get e-Alerts
Quantitative analysis of contribution of initial traps to breakdown in HfAlO/sub x//SiO/sub 2/ stacked gate dielectrics (2005)

We have demonstrated that the TDDB reliability should be predicted with the trap generation rate extracted excluding the amount of initial traps and that the initial trap cannot explain the low Weibull slope /spl beta/ observed in high-k stacks.
Wavelet-Based Medical Image Registration for Retrieval Applications (2008)

In this paper, a novel, fully automatic, multiscale wavelet-based image registration technique is proposed for image retrieval applications. We present a fast 2-D rigid registration scheme for retrieval applications. Here, the use of multiscale wavelet representation with mutual information (MI) is expected to facilitate matching of important anatomical structures at multiple resolutions. We propose to use a dyadic grid in the parameter search space for efficient computation in the multiscale domain. The proposed approach has several novel aspects including the use of MI in multiscale wavelet domain and variable bin sizes for each level of decomposition. The technique is also tested under varying noise levels. The results show high efficacy of the proposed approach.
Enhanced physician performance when using an artificial intelligence model to detect ischemic stroke on computed tomography (2023)

Abstract Acute ischemic stroke can be subtle to detect on non-contrast computed tomography imaging. We show that a novel artificial intelligence model significantly improves the performance of physicians, including ED physicians, neurologists and radiologists, in identifying and quantifying the volume of acute ischemic stroke lesions. This model may lead to improved clinical decision-making for stroke patients.
Altered hemodynamics and vascular reactivity in a mouse model with severe pericyte deficiency (2022)

Pericytes are the mural cells of the microvascular network that are in close contact with underlying endothelial cells. Endothelial-secreted PDGFB leads to recruitment of pericytes to the vessel wall, but this is disrupted in <i>Pdgfb<sup>ret/ret</sup></i> mice when the PDGFB retention motif is deleted. This results in severely reduced pericyte coverage on blood vessels. In this study, we investigated vascular abnormalities and hemodynamics in <i>Pdgfb</i><sup>ret/ret</sup> mice throughout the cerebrovascular network and in different cortical layers by <i>in vivo</i> two-photon microscopy. We confirmed that <i>Pdgfb</i><sup>ret/ret</sup> mice are severely deficient in pericytes throughout the vascular network, with enlarged brain blood vessels and a reduced number of vessel branches. Red blood cell velocity, linear density, and tube hematocrit were reduced in <i>Pdgfb</i><sup>ret/ret</sup> mice, which may impair oxygen delivery to the tissue. We also measured intravascular PO<sub>2</sub> and found that concentrations were higher in cortical Layer 2/3 in <i>Pdgfb</i><sup>ret/ret</sup> mice, indicative of reduced blood oxygen extraction. Finally, we found that <i>Pdgfb</i><sup>ret/ret</sup> mice had a reduced capacity for vasodilation in response to an acetazolamide challenge during functional MRI imaging. Taken together, these results suggest that severe pericyte deficiency can lead to vascular abnormalities and altered cerebral blood flow, reminiscent of pathologies such as arteriovenous malformations.
Novel cross-correlation technique for characterization of subpicosecond pulses from mode-locked semiconductor lasers (1993)

A diagnostic technique for repetitively pulsed lasers which is simple in application but provides subpicosecond temporal resolution is described. The method uses cross-correlation in a scanned Michelson interferometer, the electrical output of which is produced by a low-speed photodiode and a lock-in amplifier. A measurement on an actively mode-locked semiconductor laser emitting near a wavelength of 0.845 μm indicated a pulse width of 258±44 fs and a phase memory time for pulses in a train of 1.47 ns.
Nonflammable Electrolytes for Lithium-Ion Batteries Containing Dimethyl Methylphosphonate (2010)

A novel nonflammable electrolyte for lithium-ion batteries has been developed. The optimized electrolyte is composed of LiPF6 in a mixture of carbonate solvents with added dimethyl methylphosphonate as a flame retarding cosolvent and lithium bis(oxalatoborate) as an anode film forming additive. Conductivity, thermal stability, electrochemical stability, self extinguishing times, electrochemical cycling, and ex situ surface analysis of the cycled electrodes are reported. This novel electrolyte has a comparable cycling efficiency to the current state-of-the-art electrolytes for lithium-ion batteries but is nonflammable. © 2010 The Electrochemical Society.
Analysis and Identification of Biomarkers and Origin of Color in a Bright Blue Crude Oil (2010)

We describe the detailed analysis and characterization of an unusual blue crude oil and a deposit from the monoethylene glycol (MEG) regeneration unit (MRU) on an offshore crude oil production platform. To characterize the deposit and the components in the crude oil that give it such a distinct blue hue, we investigated the samples with comprehensive two-dimensional gas chromatography (GC × GC), Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), and two-dimensional (2D) fluorescence spectroscopy. Perylene, a polycyclic aromatic hydrocarbon, known to fluoresce, was identified in the crude oil with all three of these techniques. On the basis of its photochemical properties and abundance (55 ppm), we infer perylene to be the most likely source of the blue color. In addition, we were able to conclusively identify by GC × GC a suite of pentacyclic triterpenoids, of which the most abundant species was 17α(H),21β(H)-25-norhopane. The deposit is greatly enriched in these species. The presence of 25-norhopanes in a crude oil is considered as an indication for severe biodegradation.
Rapid Clot Formation and Abnormal Fibrin Structure in a Symptomatic Patient Taking Fenfluramine (2001)

A 35-year-old woman experienced symptomatic calf pain while taking a combination of fenfluramine and phentermine. All symptoms resolved when the medications were stopped, but pain returned when fenfluramine was restarted. Laboratory evaluation revealed mild elevations of aspartate aminotransferase and lactate dehydrogenase and a remarkably shortened prothrombin time (6.3 seconds). Additional studies revealed that the clots were composed of very thin fibrin fibers. All laboratory abnormalities, including the abnormal fibrin structure, completely resolved when fenfluramin was stopped. Direct addition of fenfluramine or phentermine to normal plasma did not alter either coagulation kinetics or fibrin structure, supporting the concept that the induced changes may have originated at the hepatic level. Clots composed of thin fibers are much more resistant to fibrinolysis, and could potentially put such patients at risk for thrombotic complications. This is the first report of clotting abnormalities associated with fenfluramine use. Subsequent to its use in this patient, fenfluramine was removed from clinical use due to reports of acquired valvular heart disease.
Dynamic phase-shifting electronic speckle pattern interferometer (2005)

The technique for measuring changes in diffuse surfaces using Electronic Speckle Pattern Interferometry (ESPI) is well known. We present a new electronic speckle pattern interferometer that takes advantage of a single-frame spatial phase-shifting technique to significantly reduce sensitivity to vibration and enable complete data acquisition in a single laser pulse. The interferometer was specifically designed to measure the stability of the James Webb Space Telescope (JWST) backplane. During each measurement the laser is pulsed once and four phase-shifted interferograms are captured in a single image. The signal is integrated over the 9ns pulse which is over six orders of magnitude shorter than the acquisition time for conventional interferometers. Consequently, the measurements do not suffer from the fringe contrast reduction and measurement errors that plague temporal phase-shifting interferometers in the presence of vibration. This paper will discuss the basic operating principle of the interferometer, analyze its performance and show some interesting measurements.
Curious about Others: Relational and Empathetic Curiosity for Diverse Societies (2015)

Sociable curiosity -wondering and finding out about others (empathetic curiosity), and being curious with them (relational curiosity) -can draw people together, bridging differences and social distances.This promises more than the distant connections that are increasingly recognised and endorsed as mechanisms of coping with diversity and living within societies that have been characterised as diverse.It reaches towards more active and definite engagement with others.But curiosity -associated as it is with taxonomy and therefore with exploring and sometimes disrupting and recasting categories -can also be a vehicle for more fundamental explorations of social difference.Understandings of sociable curiosity are distilled in this paper through readings of theoretical literature on curiosity, wonder and taxonomy, and through a series of more tangible encounters, drawn from experiences of anti-war activism and museum projects in the UK, which bring sociable curiosity into focus.
Enzyme‐altered Liver Cell Foci in Woodchucks Infected with Woodchuck Hepatitis Virus (1988)

The histochemical characteristics of liver cell foci in woodchucks were investigated. The foci appeared to be distributed throughout the liver and were observed only in the woodchuck hepatitis virus (WHV)-positive animals, including all 19 woodchucks with hepatocellular carcinoma(HCC), and 7 without HCC. No foci appeared in 11 WHV-negative animals. Histochemical studies revealed that liver cell foci and carcinoma cells were characterized by positive gamma-glutamyl transpeptidase (GGT) enzymatic reactions and decreased glucose-6-phosphatase enzyme activity compared to non-neoplastic liver. Furthermore, serum GGT was significantly elevated in almost all of the animals which had larger carcinomas. Ultrastructural findings of foci showed some resemblance to carcinoma cells, being characterized by abundant free ribosomes within the cytoplasm and undeveloped endoplasmic reticulum. These results suggest that the liver cell foci are potential precursors of HCC in WHV-infected animals, and that serum GGT may be a useful marker for indicating the development of carcinoma.
Apoptosis induction by aluminum phthalocyanine tetrasulfonate-based sonodynamic therapy in HL-60 cells (2015)

The present study aims to investigate sonodynamically-induced apoptosis using the phthalocyanine, chloroaluminum phthalocyanine tetrasulfonate (AlPcTS). HL-60 cells were exposed to ultrasound for up to 3 min in the absence and presence of AlPcTS. Apoptosis was analyzed by cell morphology, DNA fragmentation, and caspase-3 activity. Electron spin resonance was used to measure reactive oxygen species. The number of apoptotic cells showing membrane blebbing and cell shrinkage after combined treatment (ultrasound and AlPcTS) was significantly higher than following other treatments, including ultrasound alone and AlPcTS alone. Furthermore, DNA ladder formation, caspase-3 activation and enhanced nitroxide generation were observed in cells treated with ultrasound and AlPcTS. Sonodynamically induced apoptosis, caspase-3 activation, and nitroxide generation were significantly suppressed by histidine. The significant reduction by histidine indicated that ultrasonically generated reactive oxygen species, such as singlet oxygen, is an important mediator of sonodynamically-induced apoptosis.
Efficient 3D surveys in a jungle environment (1992)

For the last fourteen years , Caltex Pacific Indonesia (CPI) has been acquiring 3-D data over existing production fields in the jungle and/or swampy environment of Central Sumatra , Indonesia . The recent years have seen an increase in 3 -D activity in CPI which has forced an evolution towards cost reduction without jeopardizing data quality. CPI has successfully developed 3-D acquisition techniques which are operationally feasible and economically attractive . This achievement is the result of careful planning to optimize field parameters, the use of a gapped inline swath geometry, an increase in the number of channels available for recording , an increase in the rintis (Jungle cutting for acces) and drilling effort, surveying with GPS, and radio shooting . This paper wilt describe the above techniques and their advantages it will also demonstrate that the 3-D data acquired is of high quality with uniform fold , good offset and azimuth distributions, and economically reasonable for the difficult environment .
Oncogenic mutations and dysregulated pathways in obesity-associated hepatocellular carcinoma (2016)

Epidemiological studies showed that obesity and its related non-alcoholic fatty liver disease (NAFLD) promote hepatocellular carcinoma (HCC) development. We aimed to uncover the genetic alterations of NAFLD-HCC using whole-exome sequencing. We compared HCC development in genetically obese mice and dietary obese mice with wild-type lean mice fed a normal chow after treatment with diethylnitrosamine. HCC tumor and adjacent normal samples from obese and lean mice were then subjected to whole-exome sequencing. Functional and mechanistic importance of the identified mutations in Carboxyl ester lipase (Cel) gene and Harvey rat sarcoma virus oncogene 1 (Hras) was further elucidated. We demonstrated significantly higher incidences of HCC in both genetic and dietary obese mice with NAFLD development as compared with lean mice without NAFLD. The mutational signatures of NAFLD-HCC and lean HCC were distinct, with <3% overlapped. Eight metabolic or oncogenic pathways were found to be significantly enriched by mutated genes in NAFLD-HCC, but only two of these pathways were dysregulated by mutations in lean HCC. In particular, Cel was mutated significantly more frequently in NAFLD-HCC than in lean HCC. The multiple-site mutations in Cel are loss-of-function mutations, with effects similar to Cel knock-down. Mutant Cel caused accumulation of cholesteryl ester in liver cells, which led to induction of endoplasmic reticulum stress and consequently activated the IRE1α/c-Jun N-terminal kinase (JNK)/c-Jun/activating protein-1 (AP-1) signaling cascade to promote liver cell growth. In addition, single-site mutations in Hras at codon 61 were found in NAFLD-HCC but none in lean HCC. The gain-of-function mutations in Hras (Q61R and Q61K) significantly promoted liver cell growth through activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/3-phosphoinositide-dependent protein kinase-1 (PDK1)/Akt pathways. In conclusion, we have identified mutation signature and pathways in NAFLD-associated HCC. Mutations in Cel and Hras have important roles in NAFLD-associated hepatocellular carcinogenesis.
Reactive intermediate chemistry (2004)

Preface. PART 1: REACTIVE INTERMEDIATES. 1. Carbocations (R.A. McClelland). 2. Crossing the Borderline Between SN1 and SN2 Nucleophilic Substitution at Aliphatic Carbon(T.L. Amyes, et al.). 3. Carbanions (S. Gronert). 4. Radicals (M. Newcomb). 5. Non-Kekul Molecules as Reactive Intermediates (J.A. Berson). 6. Organic Radical Ions (H.D. Roth). 7. Singlet Carbenes (M. Jones Jr. and R.A. Moss). 8. Stable Singlet Carbenes (G. Bertrand). 9. Triplet Carbenes (H. Tomioka). 10. Atomic Carbon (P.B. Shevlin). 11. Nitrenes (M.S. Platz). 12. Synthetic Carbene and Nitrene Chemistry (M.P. Doyle). 13. Nitrenium Ions (D.E. Falvey). 14. Silylenes (W. Ando and N. Tokitoh). 15. Strained Hydrocarbons: Structures, Stability, and Reactivity (K.B. Wiberg). 16. Arynes (M. Winkler, et al.). PART 2: METHODS AND TEMPORAL REGIMES. 17. Matrix Isolation (T. Bally). 18. Nanosecond Laser Flash Photolysis: A Tool for Physica l Organic Chemistry (J.C. Scaiano). 19. The Picosecond Realm (E. Hilinski). 20. Reactions on the Femtosecond Time Scale (J.E. Baldwin). 21. Potential Energy Surfaces and Reaction Dynamics (B.K. Carpenter). 22. The Partnership Between Electronic Structure Calculations and Experiments in the Study of Reactive Intermediates (W.T. Borden). Index.
Hybrid-resolution multispectral imaging using color filter array (2012)

Hybrid-resolution multispectral imaging is a framework to acquire multispectral images through a reconstruction procedure using two types of measurement data with different spatial and spectral resolutions. In this paper, we propose a new method for such a framework on the basis of a full-resolution RGB image and the data obtained from an image sensor with a multispectral filter array (MSFA). In the proposed method, a small region of each image band is reconstructed as a linear combination of RGB images, where the weighting coefficients are determined using MSFA data. The effectiveness of the proposed approach is shown by simulations using spectral images of natural scenes.
Additivity in the Analysis and Design of HIV Protease Inhibitors (2009)

We explore the applicability of an additive treatment of substituent effects to the analysis and design of HIV protease inhibitors. Affinity data for a set of inhibitors with a common chemical framework were analyzed to provide estimates of the free energy contribution of each chemical substituent. These estimates were then used to design new inhibitors whose high affinities were confirmed by synthesis and experimental testing. Derivations of additive models by least-squares and ridge-regression methods were found to yield statistically similar results. The additivity approach was also compared with standard molecular descriptor-based QSAR; the latter was not found to provide superior predictions. Crystallographic studies of HIV protease−inhibitor complexes help explain the perhaps surprisingly high degree of substituent additivity in this system, and allow some of the additivity coefficients to be rationalized on a structural basis.
Synergies Between Operations Research and Quantum Information Science (2023)

This article highlights synergies between quantum information science (QIS) and operations research for QIS-curious operations researchers (and vice versa), and the author challenges the community to discover more. History: This “Challenge” paper was invited by the Editor in Chief and based on the topics raised by the author at his plenary address at the 2022 INFORMS Computing Society Conference in Tampa, Florida. Funding: This material is based on work supported by the U.S. Department of Energy, Office of Science, Office of Advanced Scientific Computing Research, Accelerated Research in Quantum Computing, Fundamental Algorithmic Research for Quantum Computing. This article has been authored by an employee of National Technology &amp; Engineering Solutions of Sandia, LLC, under Contract DE-NA0003525 with the U.S. Department of Energy (DOE).