gebhart/patrepeval huggingface dataset:
Solution-state structure of an intramolecular G-quadruplex with propeller, diagonal and edgewise loops (2012)

We herein report on the formation and high-resolution NMR solution-state structure determination of a G-quadruplex adopted by d[G(3)ATG(3)ACACAG(4)ACG(3)] comprised of four G-tracts with the third one consisting of four guanines that are intervened with non-G streches of different lengths. A single intramolecular antiparallel (3+1) G-quadruplex exhibits three stacked G-quartets connected with propeller, diagonal and edgewise loops of different lengths. The propeller and edgewise loops are well structured, whereas the longer diagonal loop is more flexible. To the best of our knowledge, this is the first high-resolution G-quadruplex structure where all of the three main loop types are present.
Evaluation of a New Silicone Adhesive Tape among Clinicians Caring for Patients with Fragile or At-Risk Skin (2014)

These results indicate that the silicone tape fills a performance-expectation gap of current acrylic tapes among users of tapes on patients with fragile or at-risk skin.
Structural investigations of ylides. Part I. Crystal and molecular structures of trimethylammoniobenzamidate and trimethylammonionitramidate: two stabilised nitrogen–nitrogen ylides (1972)

Crystal structure analyses of the title compounds (IIa) and (III) have been carried out with diffractometer data. Both were solved by direct methods and refined by least-squares techniques to R 0·072 [(IIa), 977 reflexions] and 0·078 [(III), 378 reflexions]. Crystal data are: (IIa), monoclinic, space group P21/c,Z= 4, a= 11·620(10), b= 7·928(6), c= 11·454(10)Å, β= 113·75(3)°; (III), orthorhombic, space group Pnma, Z= 4, a= 12·245(6), b= 6·718(3), c= 7·099(5)Å. The results of the analyses indicate significant charge delocalijsation on the oxygen atoms of the stabilising benzoyl- and nitro-groups respectively. In both molecules the quaternary nitrogen and delocalised anionic moieties adopt a syn-planar relationship, this conformation resulting in possible interactions between oxygen and methyl-hydrogen atoms in each case In compounds (II; a–d) temperature invariant n.m.r. spectra, consistent with a single conformation in solution, were obtained.
Epidermal Growth Factor (EGF) Treatment on Multipotential Stromal Cells (MSCs). Possible Enhancement of Therapeutic Potential of MSC (2010)

Adult bone marrow multipotential stromal cells (MSCs) hold great promise in regenerative medicine and tissue engineering. However, due to their low numbers upon harvesting, MSCs need to be expanded in vitro without biasing future differentiation for optimal utility. In this concept paper, we focus on the potential use of epidermal growth factor (EGF), prototypal growth factor for enhancing the harvesting and/or differentiation of MSCs. Soluble EGF was shown to augment MSC proliferation while preserving early progenitors within MSC population, and thus did not induce differentiation. However, tethered form of EGF was shown to promote osteogenic differentiation. Soluble EGF was also shown to increase paracrine secretions including VEGF and HGF from MSC. Thus, soluble EGF can be used not only to expand MSC in vitro, but also to enhance paracrine secretion through drug-releasing MSC-encapsulated scaffolds in vivo. Tethered EGF can also be utilized to direct MSC towards osteogenic lineage both in vitro and in vivo.
Novel Retinoic Acid Receptor Alpha Agonists for Treatment of Kidney Disease (2011)

Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA) attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs): RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1) in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN). Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN.
Oxygen permeation through electrochemical vapor deposited solid oxide membranes (1994)

Dense thin yttria doped zirconia membranes were coated on the surface of porous alumina ceramic supports by the electrochemical vapor deposition method. The oxygen permeation through these thin dense oxide membranes were measured at several different temperatures (800-1000{degrees}C) in a high temperature CVD reactor. A new approach was employed to derive theoretical equations for oxygen permeation through various types of thin dense oxide membranes. These equations, which took into account both the surface reactions and the bulk diffusion, were employed to describe the electrochemical vapor deposition kinetics and the oxygen permeation through these thin dense oxide membranes. Theoretical analysis and experimental data show that the surface permeation constant is directly related to the oxygen isotope exchange coefficient measured under equilibrium conditions. For oxygen permeation through yttria doped zirconia membranes the surface reaction becomes the rate limiting step when the film thickness approaches 0.5 {mu}m, with a maximum oxygen permeation flux of about 5x10{sup -8} mol/cm{sup 2} s at 1000{degrees}C. The dependence of the oxygen permeation flux on oxygen partial pressure and membrane thickness will be discussed for oxygen permeation through fast ionic conducting oxide membranes.
Atomic Nanotube Welders:  Boron Interstitials Triggering Connections in Double-Walled Carbon Nanotubes (2005)

Here we demonstrate that the incorporation of boron (B) atoms between double-walled carbon nanotubes (DWNTs) during thermal annealing (1400-1600 degrees C) results in covalent nanotube "Y" junctions, DWNT coalescence, and the formation of flattened multiwalled carbon nanotubes (MWNTs). These processes occur via the merging of adjacent tubes, which is triggered by B interstitial atoms. We observe that B atom interstitials between DWNTs are responsible for the rapid establishment of covalent connections between neighboring tubes (polymerization), thereby resulting in the fast annealing of the carbon cylinders with B atoms embedded in the newly created carbon nanotube network. Once B is in the lattice, tube faceting (polygonization) starts to occur, and the electronic properties are expected to change dramatically. Therefore, B atoms indeed act as atomic nanotube fusers (or welders), and this process could now be used in assembling novel electronic nanotube devices, nanotube networks, carbon nanofoams and heterojunctions exhibiting p-type electronic properties.
How to measure cognitive complexity in human-computer interaction (1996)

A framework to conceptualize measure of behaviour complexity (BC), system complexity (SC) and task complexity (TC) was developed. From this framework cognitive complexity (CC) is derived as CC=SC+TC-BC. In an empirical study to investigate different measures of cognitive complexity 6 beginners and 6 experts solved four different tasks with an interactive database management system. To analyze the empirical data recorded during the interactive sessions a special program was developed. The program's purpose and the program architecture are described. Four different approaches from the literature to measure complexity in a quantitative way were considered and discussed. Application of these four approaches were compared and tested against the empirical results of the experiment. The measure of McCabe (1976) proved to be the most effective
Structure of a c-Kit Product Complex Reveals the Basis for Kinase Transactivation (2003)

The c-Kit proto-oncogene is a receptor protein-tyrosine kinase associated with several highly malignant human cancers. Upon binding its ligand, stem cell factor (SCF), c-Kit forms an active dimer that autophosphorylates itself and activates a signaling cascade that induces cell growth. Disease-causing human mutations that activate SCF-independent constitutive expression of c-Kit are found in acute myelogenous leukemia, human mast cell disease, and gastrointestinal stromal tumors. We report on the phosphorylation state and crystal structure of a c-Kit product complex. The c-Kit structure is in a fully active form, with ordered kinase activation and phosphate-binding loops. These results provide key insights into the molecular basis for c-Kit kinase transactivation to assist in the design of new competitive inhibitors targeting activated mutant forms of c-Kit that are resistant to current chemotherapy regimes.
Sub-10-nm nanogap fabrication by silicidation (2013)

We developed a simple and reliable method for the fabrication of sub-10-nm wide nanogaps. The self-formed nanogap is based on the stoichiometric solid-state reaction between metal and Si atoms during silicidation. The nanogap width is determined by the metal layer thickness. Our proposed method provides nanogaps with either symmetric or asymmetric electrodes, as well as multiple nanogaps within one unique process step. Therefore, this method allows for high throughput and large-scale production.
Molecular Genetics of Lung Cancer (2003)

Lung cancer results from multiple changes in the genome of susceptible pulmonary cells caused by exposure to carcinogens found in tobacco smoke, the environment, or the workplace. Recent studies suggest that histologically apparent lung cancer is due to the sequential accumulation of specific genetic and morphologic changes to the normal epithelial cells of the lung. Positive signallers, such as those mediated by the oncogene RAS, and negative signallers, such as those mediated by the tumor suppressor retinoblastoma protein (RB), contribute to unchecked cell growth and proliferation. Other key molecular derangements can also be considered hallmarks of cancer, including evasion of apoptosis and senescence, angiogenesis, tissue invasion, and metastases. Epigenetic inactivation of genes via DNA methylation provides another novel way of evading normal cellular control mechanisms. The new knowledge of the human genome coupled with global methods of detecting genetic abnormalities and profiling gene expression in tumor cells may enable us to understand the signaling pathways of lung cancer cells. These are molecular targets for new cancer therapeutics such as receptor tyrosine kinase inhibitors. This information could advance risk assessment, early detection, prognosis, and therapy for lung cancer.
Mad2 transiently associates with an APC/p55Cdc complex during mitosis (1998)

Activation of the mitotic checkpoint pathway in response to mitotic spindle damage in eukaryotic cells delays the exit from mitosis in an attempt to prevent chromosome missegregation. One component of this pathway, hsMad2, has been shown in mammalian cells to physically associate with components of a ubiquitin ligase activity (termed the anaphase promoting complex or APC) when the checkpoint is activated, thereby preventing the degradation of inhibitors of the mitotic exit machinery. In the present report, we demonstrate that the inhibitory association between Mad2 and the APC component Cdc27 also takes place transiently during the early stages of a normal mitosis and is lost before mitotic exit. We also show that Mad2 associates with the APC regulatory protein p55Cdc in mammalian cells as has been reported in yeast. In contrast, however, this complex is present only in nocodazole-arrested or early mitotic cells and is associated with the APC as a Mad2/p55Cdc/Cdc27 ternary complex. Evidence for a Mad2/Cdc27 complex that forms independent of p55Cdc also is presented. These results suggest a model for the regulation of the APC by Mad2 and may explain how the spindle assembly checkpoint apparatus controls the timing of mitosis under normal growth conditions.
Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease (2003)

Intestinal mucosal damage in the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) involves reactive oxygen metabolites (ROMs). ROMs are neutralized by endogenous antioxidant enzymes in a carefully balanced two-step pathway. Superoxide dismutases (SODs) convert superoxide anion to hydrogen peroxide (H(2)O(2)), which is subsequently neutralized to water by catalase (CAT) or glutathione peroxidase (GPO). Remarkably changed expression levels of the three isoforms of SOD in paired non-inflamed and inflamed mucosae from CD and UC patients have been previously reported in comparison to normal control mucosa. Most notable was the strong up-regulation of Mn-SOD in inflamed epithelium. It was hypothesized that in order to provide optimal protection against ROM-mediated damage, these changes should be coordinately counterbalanced by an increased H(2)O(2)-neutralizing capacity. Therefore, the same tissue samples were used to assess the levels, activities, and/or localization of the most prominent mucosal H(2)O(2)-related antioxidants CAT, GPO, glutathione (GSH), myeloperoxidase (MPO), and metallothionein (MT). Quantitative measurements showed that in both CD and UC patients, intestinal inflammation was associated with increased activities of CAT, GPO, and MPO, whereas the mucosal GSH content was unaffected and the concentration of MT was decreased. Despite this overall increase in mucosal H(2)O(2)-metabolizing enzyme capacity, immunohistochemical analysis revealed a differentially disturbed antioxidant balance in IBD epithelium and lamina propria. In the lamina propria, the risk of direct H(2)O(2)-mediated damage seemed to be restrained by the increasing numbers of CAT- and MPO-positive monocytes/macrophages and neutrophils that infiltrated the inflamed areas. On the other hand, MPO overexpression might increase the lamina propria levels of hypochlorous acid, a stable ROM with multiple pro-inflammatory effects. In the epithelium, the number of cells that expressed CAT remained unchanged during inflammation and GPO was found in only a very low and constant number of epithelial cells. In addition, the inflamed epithelium displayed decreased expression of the hydroxyl radical (OH(*)) scavenger MT. In view of the high epithelial SOD levels in inflamed IBD epithelium, it is speculated that the efficient removal of excess H(2)O(2) is hampered in these cells, thereby increasing not only the risk of detrimental effects of H(2)O(2) directly, but also those of its extremely reactive derivatives such as OH(*). Taken together, the results suggest an imbalanced and inefficient endogenous antioxidant response in the intestinal mucosa of IBD patients, which may contribute to both the pathogenesis and the perpetuation of the inflammatory processes.
On the hunt for helminths: innate immune cells in the recognition and response to helminth parasites (2008)

The generation of protective immunity to helminth parasites is critically dependent upon the development of a CD4(+) T helper type 2 cytokine response. However, the host-parasite interactions responsible for initiating this response are poorly understood. This review will discuss recent advances in our understanding of how helminth-derived products are recognized by innate immune cells. Specifically, interactions between helminth excretory/secretory products and host Toll-like receptors and lectins will be discussed as well as the putative functions of helminth proteases and chitin in activating and recruiting innate immune cells. In addition, the functional significance of pattern recognition by epithelial cells, granulocytes, dendritic cells and macrophages including expression of alarmins, thymic stromal lymphopoetin, interleukin (IL)-25, IL-33 and Notch ligands in the development of adaptive anti-parasite Th2 cytokine responses will be examined.
Cytomegalovirus-mediated induction of antisense mRNA expression to UL44 inhibits virus replication in an astrocytoma cell line: identification of an essential gene (1995)

We have used an antisense RNA approach in the analysis of gene function in human cytomegalovirus (HCMV). An astrocytoma cell line (U373-MG) that is permissive for virus replication was permanently transfected with a construct bearing sequence from HCMV UL44 (coding for the major late DNA-binding protein, ppUL44, also known as pp52 or ICP36) in an antisense orientation and under the control of the immediate-early enhancer-promoter element. Upon HCMV infection at a high multiplicity, we found a marked reduction in UL44 protein products (the ICP36 family of proteins) in established cell transfectants and a strong inhibition of virus yield in infected-cell supernatants at two weeks postinfection, while herpes simplex virus replication was not affected. In infected cells, viral DNA replication was strongly inhibited. While gene products such as pUS22 and pUL32 were also inhibited, pUL123 and pUL82 accumulated in the infected cells over time. Our data suggest an essential role for the UL44 family of proteins in HCMV replication and represent a model of virus inhibition by virus-induced antisense RNA synthesis in genetically modified cells.
Mouse Models of Abdominal Aortic Aneurysms (2004)

Many mouse models of abdominal aortic aneurysms have been developed that use a diverse array of methods for producing the disease, including genetic manipulation and chemical induction. These models could provide insight into potential mechanisms in the development of this disease. Although experimental studies on abdominal aortic aneurysms (AAAs) have used a variety of mammalian and avian approaches, there is an increasing reliance on the use of mice. The models recapitulate some facets of the human disease including medial degeneration, inflammation, thrombus formation, and rupture. Most of the mouse models of AAA are evoked either by genetically defined approaches or by chemical means. The genetic approaches are spontaneous and engineered mutations. These include defects in extracellular matrix maturation, increased degradation of elastin and collagen, aberrant cholesterol homeostasis, and enhanced production of angiotensin peptides. The chemical approaches include the intraluminal infusion of elastase, periaortic incubations of calcium chloride, and subcutaneous infusion of AngII. A common feature of these models is the reduction of AAA incidence and severity by the prophylactic administration of matrix metalloproteinase (MMP) inhibitors or genetically engineered deficiencies of specific members of this proteolytic protein family. The validation of mouse models of AAAs will provide insight into the mechanisms of progression of the human disease.
Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study. (1992)

increased gluconeogenesis is responsible for the increased whole body glucose production in type II diabetes mellitus after an overnight fast.
Integrating Genetic Approaches into the Discovery of Anticancer Drugs (1997)

The discovery of anticancer drugs is now driven by the numerous molecular alterations identified in tumor cells over the past decade. To exploit these alterations, it is necessary to understand how they define a molecular context that allows increased sensitivity to particular compounds. Traditional genetic approaches together with the new wealth of genomic information for both human and model organisms open up strategies by which drugs can be profiled for their ability to selectively kill cells in a molecular context that matches those found in tumors. Similarly, it may be possible to identify and validate new targets for drugs that would selectively kill tumor cells with a particular molecular context. This article outlines some of the ways that yeast genetics can be used to streamline anticancer drug discovery.
Association of heterogeneous nuclear ribonucleoprotein A1 and C proteins with reiterated AUUUA sequences. (1993)

Post-transcriptional regulatory mechanisms have been shown to play a major role in gene expression in eukaryotic cells. The presence of a reiterated pentamer (AUUUA) in the 3'-untranslated region (UTR) of mRNAs encoding lymphokines, cytokines, transcription factors, and proto-oncogenes has been shown to be associated with rapid turnover and translation attenuation. Cytoplasmic proteins (70, 50, 43, 36, and 25 kDa) capable of specifically binding to RNAs containing these AU-rich sequences were identified in human peripheral blood T lymphocytes. Levels of the 36-kDa protein were markedly increased following transcriptional, but not translational inhibition, a feature recently reported for hnRNP A1, a protein of comparable mass. Antibodies directed against heterogeneous nuclear ribonucleoproteins (hnRNPs) A1 and C immunoprecipitated 36- and 43-kDa proteins that had bound the AUUUA-rich region contained in the 3'-UTR of granulocyte-macrophage colony-stimulating factor mRNA. Recombinant hnRNP A1 was shown to preferentially bind to RNAs containing AUUUA sequences in a specific manner, and displayed comparable patterns to the 36-kDa AU-specific binding proteins following partial proteolysis. These data identify for the first time hnRNP A1 and C as cytoplasmic proteins in human lymphocytes that are capable of specifically associating with reiterated AUUUA sequences present in the 3'-UTR of labile mRNAs. As such, they may play a role as trans-acting factors in the modulation of cytoplasmic mRNA turnover and translation, in addition to their previously characterized roles as pre-mRNA binding proteins involved in nuclear mRNA processing.
A Six Degree-of-Freedom God-Object Method for Haptic Display of Rigid Bodies (2006)

This paper describes a generalization of the god-object method for haptic interaction between rigid bodies. Our approach separates the computation of the motion of the six degree-of-freedom god-object from the computation of the force applied to the user. The motion of the god-object is computed using continuous collision detection and constraint-based quasi-statics, which enables high-quality haptic interaction between contacting rigid bodies. The force applied to the user is computed using a novel constraint-based quasi-static approach, which allows us to suppress force artifacts typically found in previous methods. Our approach has been implemented on a 3.2 GHz Xeon bi-processor and has been successfully tested on complex benchmarks. Our results show that the separation into asynchronous processes allows us to satisfy the different update rates required by the haptic and the visual displays. The constraint-based force applied to the user, which handles any number of simultaneous contact points, is typically computed within a few microseconds, while the update of the configuration of the rigid god-object is performed within a few milliseconds for rigid bodies containing up to tens of thousands of triangles.