gebhart/patrepeval huggingface dataset:
Low-cost multi-touch sensing through frustrated total internal reflection (2005)

This paper describes a simple, inexpensive, and scalable technique for enabling high-resolution multi-touch sensing on rear-projected interactive surfaces based on frustrated total internal reflection. We review previous applications of this phenomenon to sensing, provide implementation details, discuss results from our initial prototype, and outline future directions.
The Convergence of Graphics and Imaging (1998)

Over twenty years ago a SIGGRAPH panel session addressed the convergence of computer graphics and image processing. At that time the emphasis was on low‐level operations such as filtering to avoid anti‐aliasing, and related psycho‐physics issues. More recently, Graphics and Imaging are converging at a higher level as we move toward blending the synthetic world of computer‐generated images with the real world of computer‐captured images. In this talk we describe several research directions that relate to this convergence, and illustrate with specific examples of work at MERL – A Mitsubishi Electric Research Laboratory. These research directions are: Analyzing images of the human face to determine identity and orientation and ultimately to reconstruct the shape of the face. Reconstruction of static and dynamic 3D geometries from 2D images separated in time or space: here the objective is to take multiple images of a real‐world scene and recreate the 3D geometry of the scene. If objects in the scene are moving, then the objective is extracting the dynamic geometry. Once the geometry has been reconstructed, editing and relighting of the scene becomes possible. Display of 3D scalar fields (also known as volume graphics) concerns 3D as opposed to 2D images, such as CT and MRI scans. These scans can be thought of as 3D images in that they are point samples of a 3D scalar field, just as a computer‐captured image is a point sample of a 2D sample field. The objective of volume graphics is to create and display the 3D geometries that underly 3D images. An inexpensive yet real‐time (30 fps for a 256 x 256 x 256 image) implementation of Pfister and Kaufman’s Cube‐4 rendering architecture will be described.
A review on polymeric hydrogel membranes for wound dressing applications: PVA-based hydrogel dressings (2017)

This review presents the past and current efforts with a brief description on the featured properties of hydrogel membranes fabricated from biopolymers and synthetic ones for wound dressing applications. Many endeavors have been exerted during past ten years for developing new artificial polymeric membranes, which fulfill the demanded conditions for the treatment of skin wounds. This review mainly focuses on representing specifications of ideal polymeric wound dressing membranes, such as crosslinked hydrogels compatible with wound dressing purposes. But as the hydrogels with single component have low mechanical strength, recent trends have offered composite or hybrid hydrogel membranes to achieve the typical wound dressing requirements.
A synthetic peptide mimic of plasma apolipoprotein E that binds the LDL receptor. (1991)

Human plasma apolipoprotein E (apoE) is a low density lipoprotein (LDL) receptor ligand. It targets cholesterol-rich lipoproteins to LDL receptors on both hepatic and peripheral cells. The region of apoE responsible for its binding to the LDL receptor has been localized to amino acids 140-160. An apoE 141-155 monomeric peptide and a dimeric 141-155 tandem peptide were synthesized and tested for their inhibition of 125I-LDL degradation by human fibroblasts and human monocytic-like cells, THP-1. The monomer had no activity at 250 microM, but the dimer inhibited 125I-LDL degradation by 50% at 5 microM. The inhibition was specific for the LDL receptor because the dimer did not inhibit the degradation of 125I-acetylated LDL by scavenger receptors expressed by phorbol ester-stimulated THP-1 cells. As reported for native apoE, amino acid substitutions of Lys-143----Ala, Leu-144----Pro, and Arg-150----Ala decreased the inhibitory effectiveness of the dimer. Furthermore, a trimer of the 141-155 sequence had a 20-fold greater inhibitory activity than the dimer. Studies with a radioiodinated dimer indicated that some of the inhibitory activity could be a result of the interaction of the dimer with LDL. However, direct binding of the 125I-dimeric peptide to THP-1 cells was observed as well. This binding was time-dependent, linear with increasing cell number, Ca(2+)- but not Mg(2+)-dependent, saturable, inhibited by lipoproteins, and increased by preculture of the cells in lipoprotein-depleted medium. Therefore, a synthetically prepared dimeric repeat of amino acid residues 141-155 of apoE binds the LDL receptor.
Gene ontology analysis for RNA-seq: accounting for selection bias (2010)

We present GOseq, an application for performing Gene Ontology (GO) analysis on RNA-seq data. GO analysis is widely used to reduce complexity and highlight biological processes in genome-wide expression studies, but standard methods give biased results on RNA-seq data due to over-detection of differential expression for long and highly expressed transcripts. Application of GOseq to a prostate cancer data set shows that GOseq dramatically changes the results, highlighting categories more consistent with the known biology.
Impact of Mitochondrial Reactive Oxygen Species and Apoptosis Signal–Regulating Kinase 1 on Insulin Signaling (2006)

Tumor necrosis factor (TNF)-alpha inhibits insulin action; however, the precise mechanisms are unknown. It was reported that TNF-alpha could increase mitochondrial reactive oxygen species (ROS) production, and apoptosis signal-regulating kinase 1 (ASK1) was reported to be required for TNF-alpha-induced apoptosis. Here, we examined roles of mitochondrial ROS and ASK1 in TNF-alpha-induced impaired insulin signaling in cultured human hepatoma (Huh7) cells. Using reduced MitoTracker Red probe, we confirmed that TNF-alpha increased mitochondrial ROS production, which was suppressed by overexpression of either uncoupling protein-1 (UCP)-1 or manganese superoxide dismutase (MnSOD). TNF-alpha significantly activated ASK1, increased serine phosphorylation of insulin receptor substrate (IRS)-1, and decreased insulin-stimulated tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt, and all of these effects were inhibited by overexpression of either UCP-1 or MnSOD. Similar to TNF-alpha, overexpression of wild-type ASK1 increased serine phosphorylation of IRS-1 and decreased insulin-stimulated tyrosine phosphorylation of IRS-1, whereas overexpression of dominant-negative ASK1 ameliorated these TNF-alpha-induced events. In addition, TNF-alpha activated c-jun NH(2)-terminal kinases (JNKs), and this observation was partially inhibited by overexpression of UCP-1, MnSOD, or dominant-negative ASK1. These results suggest that TNF-alpha increases mitochondrial ROS and activates ASK1 in Huh7 cells and that these TNF-alpha-induced phenomena contribute, at least in part, to impaired insulin signaling.
Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats. (1998)

Constitutive nitric oxide synthase (cNOS) with insufficient cofactor (6R)-5,6,7,8-tetrahydrobiopterin (H4B) may generate damaging superoxide (O2-). This study was designed to determine whether cNOS-dependent generation of O2- occurs in spontaneously hypertensive rats (SHR) before the onset of hypertension. Aortas from 4-wk-old SHR and Wistar-Kyoto rats were used. cNOS was stimulated by calcium ionophore A23187. In situ measurements of nitric oxide and hydrogen peroxide by electrochemical sensors and O2- production by chemiluminescence method were performed. Isometric tension was continuously recorded. H4B by high performance liquid chromatography and [3H]citrulline assay were determined in homogenized tissue. The A23187-stimulated production of O2- and its superoxide dismutase product hydrogen peroxide were significantly higher, whereas nitric oxide release was reduced in SHR aortas, with opposite results in the presence of exogenous H4B. Furthermore, NG-monomethyl-L-arginine inhibited the generation of cNOS-dependent O2- by approximately 70%. Natural H4B levels were similar in both strains; however, equivalent cNOS activity required additional H4B in SHR. The endothelium-dependent relaxations to A23187 were significantly inhibited by catalase, and enhanced by superoxide dismutase, only in SHR; however, these enzymes had no effect in the presence of H4B. Thus, dysfunctional cNOS may be a source of O2- in prehypertensive SHR and contribute to the development of hypertension and its vascular complications.
Structure-anticonvulsant activity relationships of cannabidiol analogs. (1987)

Cannabidiol (CBD) exhibits anticonvulsant activity in experimental animals and in man. As part of a structure-activity study, analogs were prepared wherein the terpene unit, the aryl unit, and/or the side chain were modified. Thus, several pinenyl and carenyl derivatives, aryl ethers and acetates, and a variety of 1",1"-dialkylhexyl and 1",1"-dialkylheptyl analogs were synthesized. The compounds were evaluated for anti-convulsant activity in seizure susceptible (AGS) rats and for neurotoxicity in the rat rotorod (ROT) test. Comparisons of stereoisomers of CBD and several analogs revealed a general lack of stereoselectivity for anticonvulsant and other CNS properties of this class of compounds.
Energetic origins of specificity of ligand binding in an interior nonpolar cavity of T4 lysozyme (1995)

To determine the constraints on interactions within the core of a folded protein, we have analyzed the binding of 91 different compounds to an internal cavity created in the interior of phage T4 lysozyme by site-directed mutagenesis [Eriksson et al. (1992a) Nature 355, 371-373]. The cavity is able to accommodate a variety of small, mainly nonpolar, ligands. Molecules which do not appear to bind include those that are very polar, those that are too large, and those that have appropriate volume and polarity but inappropriate shape. Calorimetric analysis of 16 of these ligands reveals that their free energies of binding are poorly correlated with their solvent-transfer free energies. In addition, their enthalpies of binding are much larger than expected on the basis of transfer of the ligands from an aqueous to a nonpolar liquid phase. The binding energetics were analyzed by dividing the reaction into three processes: desolvation, immobilization, and packing. This analysis indicates that all three processes contribute to binding specificity. For a subset of these ligands that are structurally related, however, packing interactions in the protein interior are well modeled by the interactions of the ligands with octanol.
A conserved protonation-dependent switch controls drug binding in the Abl kinase (2008)

In many protein kinases, a characteristic conformational change (the "DFG flip") connects catalytically active and inactive conformations. Many kinase inhibitors--including the cancer drug imatinib--selectively target a specific DFG conformation, but the function and mechanism of the flip remain unclear. Using long molecular dynamics simulations of the Abl kinase, we visualized the DFG flip in atomic-level detail and formulated an energetic model predicting that protonation of the DFG aspartate controls the flip. Consistent with our model's predictions, we demonstrated experimentally that the kinetics of imatinib binding to Abl kinase have a pH dependence that disappears when the DFG aspartate is mutated. Our model suggests a possible explanation for the high degree of conservation of the DFG motif: that the flip, modulated by electrostatic changes inherent to the catalytic cycle, allows the kinase to access flexible conformations facilitating nucleotide binding and release.
CYTOTOXIC EFFECTOR MOLECULE GENE EXPRESSION IN ACUTE RENAL ALLOGRAFT REJECTION (2001)

Fas ligand may be useful as an early marker of therapy-resistant acute rejection. Cells that express Fas ligand but not classical soluble cytotoxic molecules might influence clinical outcome of acute rejection episodes.
Strategies for Design of Non Peptide CCK1R Agonist/Antagonist Ligands (2007)

This review mainly covers last five year literature on CCK1R agonists and antagonists. These CCK1R ligands have been found following the two usual and complementary strategies for drug discovery: rational design based on structure activity relationships on the CCK-7 and CCK-4 peptide sequences of the endogenous ligands and random screening of diverse compounds, followed by hit optimization. The first group includes: chimeric bifunctional opioid/CCK peptides, designed as opioid agonists with balanced CCK1R/CCK2R antagonist activity for the treatment of neuropathic pain, antagonist and agonist dipeptoids, and 1,3-dioxoperhydropyrido[1,2-c]pyrimidine- and anthranilic acid-based antagonists. Among the ligands derived from random screening, a few new 1,4-benzodiazepine-, 1,5-benzodiazepine-, and five member ring heterocycle-based CCK1R ligands have been reported. Finally, taking into account the importance of receptor mapping studies for ligand optimization and future precise de novo receptor structure-based design of new selective and more effective ligands, the most significant conclusions of these studies have also been reviewed.
Speculative lock elision: enabling highly concurrent multithreaded execution (2001)

Serialization of threads due to critical sections is a fundamental bottleneck to achieving high performance in multithreaded programs. Dynamically, such serialization may be unnecessary because these critical sections could have safely executed concurrently without locks. Current processors cannot fully exploit such parallelism because they do not have mechanisms to dynamically detect such false inter-thread dependences. We propose Speculative Lock Elision (SLE), a novel micro-architectural technique to remove dynamically unnecessary lock-induced serialization and enable highly concurrent multithreaded execution. The key insight is that locks do not always have to be acquired for a correct execution. Synchronization instructions are predicted as being unnecessary and elided. This allows multiple threads to concurrently execute critical sections protected by the same lock. Misspeculation due to inter-thread data conflicts is detected using existing cache mechanisms and rollback is used for recovery. Successful speculative elision is validated and committed without acquiring the lock. SLE can be implemented entirely in microarchitecture without instruction set support and without system-level modifications, is transparent to programmers, and requires only trivial additional hardware support. SLE can provide programmers a fast path to writing correct high-performance multithreaded programs.
Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice (2008)

The vitamin D endocrine system is essential for calcium and bone homeostasis. The precise mode of action and the full spectrum of activities of the vitamin D hormone, 1,25-dihydroxyvitamin D [1,25-(OH)(2)D], can now be better evaluated by critical analysis of mice with engineered deletion of the vitamin D receptor (VDR). Absence of a functional VDR or the key activating enzyme, 25-OHD-1alpha-hydroxylase (CYP27B1), in mice creates a bone and growth plate phenotype that mimics humans with the same congenital disease or severe vitamin D deficiency. The intestine is the key target for the VDR because high calcium intake, or selective VDR rescue in the intestine, restores a normal bone and growth plate phenotype. The VDR is nearly ubiquitously expressed, and almost all cells respond to 1,25-(OH)(2)D exposure; about 3% of the mouse or human genome is regulated, directly and/or indirectly, by the vitamin D endocrine system, suggesting a more widespread function. VDR-deficient mice, but not vitamin D- or 1alpha-hydroxylase-deficient mice, and man develop total alopecia, indicating that the function of the VDR and its ligand is not fully overlapping. The immune system of VDR- or vitamin D-deficient mice is grossly normal but shows increased sensitivity to autoimmune diseases such as inflammatory bowel disease or type 1 diabetes after exposure to predisposing factors. VDR-deficient mice do not have a spontaneous increase in cancer but are more prone to oncogene- or chemocarcinogen-induced tumors. They also develop high renin hypertension, cardiac hypertrophy, and increased thrombogenicity. Vitamin D deficiency in humans is associated with increased prevalence of diseases, as predicted by the VDR null phenotype. Prospective vitamin D supplementation studies with multiple noncalcemic endpoints are needed to define the benefits of an optimal vitamin D status.
Transmembrane Insertion of theToxoplasma gondiiGRA5 Protein Occurs after Soluble Secretion into the Host Cell (1999)

The intracellular parasite Toxoplasma gondii resides within a specialized compartment, the parasitophorous vacuole (PV), that resists fusion with host cell endocytic and lysosomal compartments. The PV is extensively modified by secretion of parasite proteins, including the dense granule protein GRA5 that is specifically targeted to the delimiting membrane of the PV (PVM). We show here that GRA5 is present both in a soluble form and in hydrophobic aggregates. GRA5 is secreted as a soluble form into the PV after which it becomes stably associated with the PVM. Topological studies demonstrated that GRA5 was inserted into the PVM as a transmembrane protein with its N-terminal domain extending into the cytoplasm and its C terminus in the vacuole lumen. Deletion of 8 of the 18 hydrophobic amino acids of the single predicted transmembrane domain resulted in the failure of GRA5 to associate with the PVM; yet it remained correctly packaged in the dense granules and was secreted as a soluble protein into the PV. Collectively, these studies demonstrate that the secretory pathway in Toxoplasma is unusual in two regards; it allows soluble export of proteins containing typical transmembrane domains and provides a mechanism for their insertion into a host cell membrane after secretion from the parasite.
Measurement of the current–distance relationship using a novel refractory interaction technique (2009)

It is important to know the spatial extent of neural activation around the stimulating electrodes when using extracellular electrical stimulation for the determination of the structure and function of neural circuit connections or for the restoration of function. The current-distance relationship quantifies the relationship between the threshold current for excitation of a neuron, I(th), and the distance between the electrode and the neuron, r, with two parameters: the offset, I(0), and the current-distance constant, k, with a quadratic equation, I(th)(r) = I(0) + kr(2). We proposed a new method to determine the parameters of the current-distance relationship, and thereby estimate the spatial extent of activation, based on the refractory interaction technique. Refractory interaction is a method that exploits the interaction between the regions of activation produced by two electrodes, when the second stimulus is delivered while neurons activated by the first electrode are in their refractory period. Computer simulations of electrical stimulation of a population of nerve fibers were used to determine the accuracy of the method. The mean relative error in k was 19% and in I(0) was 17%, and the spatial extent of stimulation could be determined with an absolute error of 19 microm and a relative error less than 11%. Subsequently, the method was applied to measure the current-distance properties of peripheral motor nerve fibers and indicated that k = 27 microA mm(-2) and I(0) = 49 microA. This method provided robust estimates of the current-distance properties, and provides a means to determine the spatial extent of activation by extracellular stimulation.
Transformation of Cinchona Alkaloids into 1-N-Oxide Derivatives by Endophytic Xylaria sp. Isolated from Cinchona pubescens. (2003)

The microbial transformation of four Cinchona alkaloids (quinine, quinidine, cinchonidine, and cinchonine) by endophytic fungi isolated from Cinchona pubescens was investigated. The endophytic filamentous fungus Xylaria sp. was found to transform the Cinchona alkaloids into their 1-N-oxide derivatives.
Regiospecific C-Acylation of Pyrroles and Indoles Using N-Acylbenzotriazoles (2003)

Reactions of pyrrole (2) or 1-methylpyrrole (4) with readily available N-acylbenzotriazoles 1a-g (RCOBt, where R = 4-tolyl, 4-nitrophenyl, 4-diethylaminophenyl, 2-furyl, 2-pyridyl, 2-indolyl, or 2-pyrrolyl) in the presence of TiCl(4) produced 2-acylpyrroles 3a-g and 5a-g in good to excellent yields. 1-Triisopropylsilylpyrrole (6) under the same conditions gave the respective 3-acylpyrroles 7a-g. Similarly, indole (9) and 1-methylindole (11) gave the corresponding 3-acylated derivatives 10a-g and 12a-g. These results demonstrate that N-acylbenzotriazoles such as 1c,f,g are mild, regioselective, and regiospecific C-acylating agents of particular utility when the corresponding acid chlorides are not readily available.
Clinical significance of co-expression of VEGF-C and VEGFR-3 in non-small cell lung cancer. (2003)

In NSCLC, VEGF-C and VEGFR-3 are related to the lymphangiogenesis, angiogenesis, and occurrence and development of lung cancers. VEGF-C expression could be a useful predictor of poor prognosis in NSCLC.
Invertases. Primary Structures, Functions, and Roles in Plant Development and Sucrose Partitioning (1999)

One of the key features of plants is their ability to reduce carbon dioxide in the presence of sunlight and water to sugars, and the subsequent transport of assimilated carbon to the nonphotosynthetic tissues (sink tissues). In most plants, the transported sugar is Suc, a nonreducing disaccharide,
Synthesis of Substituted 3-Pyridinecarboxaldehydes (1987)

Reaction de Vilsmeier sur des dihydro-1,2- et -1,4 pyridinecarboxylates-1 de phenyle suivie d'aromatisation par S 8
CRISPR/Cas9 systems targeting β-globin and CCR5 genes have substantial off-target activity (2013)

The ability to precisely modify endogenous genes can significantly facilitate biological studies and disease treatment, and the clustered regularly interspaced short palindromic repeats (CRISPR) systems have the potential to be powerful tools for genome engineering. However, the target specificity of CRISPR systems is largely unknown. Here we demonstrate that CRISPR/Cas9 systems targeting the human hemoglobin β and C-C chemokine receptor type 5 genes have substantial off-target cleavage, especially within the hemoglobin δ and C-C chemokine receptor type 2 genes, respectively, causing gross chromosomal deletions. The guide strands of the CRISPR/Cas9 systems were designed to have a range of mismatches with the sequences of potential off-target sites. Off-target analysis was performed using the T7 endonuclease I mutation detection assay and Sanger sequencing. We found that the repair of the on-and off-target cleavage resulted in a wide variety of insertions, deletions and point mutations. Therefore, CRISPR/Cas9 systems need to be carefully designed to avoid potential off-target cleavage sites, including those with mismatches to the 12-bases proximal to the guide strand protospacer-adjacent motif.