gebhart/patrepeval huggingface dataset:
A Randomized Trial Comparing the Pharmacokinetics, Safety, and Tolerability of DFN‐02, an Intranasal Sumatriptan Spray Containing a Permeation Enhancer, With Intranasal and Subcutaneous Sumatriptan in Healthy Adults (2016)

In healthy subjects, DFN-02, an intranasal spray containing 10 mg sumatriptan plus DDM, had a more rapid absorption profile than commercially available intranasal sumatriptan 20 mg, and systemic exposure from a single-dose administration of DFN-02 was similar to 4 mg SC sumatriptan and two-thirds that of 6 mg SC sumatriptan. With DFN-02, plasma sumatriptan peaked 5 minutes earlier than with both subcutaneous formulations. Systemic exposure to sumatriptan was similar with DFN-02 and 4 mg subcutaneous sumatriptan; both yielded lower systemic exposure than 6 mg subcutaneous sumatriptan. Systemic exposure to DFN-02's excipient DDM was short-lived. DFN-02's safety and tolerability appear to be comparable to subcutaneous sumatriptan. Addition of a permeation enhancer improved the absorption profile compared with commercially available intranasal sumatriptan 20 mg.
Stimulation of in vivo angiogenesis by cytokine-loaded hyaluronic acid hydrogel implants and potential gene expression mechanisms for new vessel growth (2003)

As a first step to developing cytokine-impregnated hydrogels capable of promoting desired physiologic responses, we have tested in vivo angiogenesis in a mouse model. Hyaluronic acid (HA) hydrogel samples pre-loaded with vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) were surgically implanted in an ear pocket in the mouse. The implants were then retrieved at 7 and 14 days post surgery, and the number of ingrowing microvessels evaluated by direct counting. As compared to contralateral controls, we show that released degrading hyaluronan alone is itself an effective stimulus for new vessel growth. Pre-loading of the gel with VEGF, however, dramatically augments the rate of new microvessel growth, resulting in a 2.3-fold increase in neovascularization over the sum of the rates produced by HA and VEGF individually. In contrast, although bFGF alone greatly augments vessel growth, no such potentiation effect was observed between bFGF and HA. We present physiologic data demonstrating vessel growth and correlate those data with gene expression changes measured by microarray analysis. The results show that HA-cytokine combinations can be designed to optimize angiogenesis, and suggest potential mechanisms by which angiogenic vessel proliferation may occur.
Genetic testing for retinal dystrophies and dysfunctions: benefits, dilemmas and solutions (2007)

Human retinal dystrophies have unparalleled genetic and clinical diversity and are currently linked to more than 185 genetic loci. Genotyping is a crucial exercise, as human gene-specific clinical trials to study photoreceptor rescue are on their way. Testing confirms the diagnosis at the molecular level and allows for a more precise prognosis of the possible future clinical evolution. As treatments are gene-specific and the 'window of opportunity' is time-sensitive; accurate, rapid and cost-effective genetic testing will play an ever-increasing crucial role. The gold standard is sequencing but is fraught with excessive costs, time, manpower issues and finding non-pathogenic variants. Therefore, no centre offers testing of all currently 132 known genes. Several new micro-array technologies have emerged recently, that offer rapid, cost-effective and accurate genotyping. The new disease chips from Asper Ophthalmics (for Stargardt dystrophy, Leber congenital amaurosis [LCA], Usher syndromes and retinitis pigmentosa) offer an excellent first pass opportunity. All known mutations are placed on the chip and in 4 h a patient's DNA is screened. Identification rates (identifying at least one disease-associated mutation) are currently approximately 70% (Stargardt), approximately 60-70% (LCA) and approximately 45% (Usher syndrome subtype 1). This may be combined with genotype-phenotype correlations that suggest the causal gene from the clinical appearance (e.g. preserved para-arteriolar retinal pigment epithelium suggests the involvement of the CRB1 gene in LCA). As approximately 50% of the retinal dystrophy genes still await discovery, these technologies will improve dramatically as additional novel mutations are added. Genetic testing will then become standard practice to complement the ophthalmic evaluation.
Length-encoded multiplex binding site determination: application to zinc finger proteins. (1994)

The screening of combinatorial libraries is becoming a powerful method for identifying or refining the structures of ligands for binding proteins, enzymes, and other receptors. We describe an oligonucleotide library search procedure in which the identity of each member is encoded in the length of oligonucleotides. This encoding scheme allows binding-site preferences to be evaluated via DNA length determination by denaturing gel electrophoresis. We have applied this method to determine the binding-site preferences for 18 Cys2His2 zinc finger domains as the central domain within a fixed context of flanking zinc fingers. An advantage of the method is that the relative affinities of all members of the library can be estimated in addition to simply determining the sequence of the optimal or consensus ligand. The zinc finger domain specificities determined will be useful for modular zinc finger protein design.
Forming Electrical Networks in Three Dimensions by Self-Assembly (2000)

Self-assembly of millimeter-scale polyhedra, with surfaces patterned with solder dots, wires, and light-emitting diodes, generated electrically functional, three-dimensional networks. The patterns of dots and wires controlled the structure of the networks formed; both parallel and serial connections were generated.
ABT-751, a novel tubulin-binding agent, decreases tumor perfusion and disrupts tumor vasculature (2009)

ABT-751 is an orally bioavailable tubulin-binding agent that is currently under clinical development for cancer treatment. In preclinical studies, ABT-751 showed antitumor activity against a broad spectrum of tumor lines including those resistant to conventional chemotherapies. In this study, we investigated the antivascular properties of ABT-751 in a rat subcutaneous tumor model using dynamic contrast-enhanced magnetic resonance imaging. A single dose of ABT-751 (30 mg/kg, intravenously) induced a rapid, transient reduction in tumor perfusion. After 1 h, tumor perfusion decreased by 57% before recovering to near pretreatment levels within 6 h. In contrast, ABT-751 produced little change in muscle perfusion at either time point. To further elucidate mechanisms of drug action at the cellular level, we examined the effects of ABT-751 on endothelial cells using an in-vitro assay. ABT-751, at concentrations corresponding to plasma levels achieved in vivo, caused endothelial cell retraction and significant loss of microtubules within 1 h. The severity of these morphological changes was dose-dependent but reversible within 6 h after the discontinuation of the drug. Taken together, these results show that ABT-751 is a tubulin-binding agent with antivascular properties. Microtubule disruption and morphological changes in vascular endothelial cells may be responsible, at least in part, for the dysfunction of tumor blood vessels after ABT-751 treatment.
Synthesis and characterization of a series of diarylguanidines that are noncompetitive N-methyl-D-aspartate receptor antagonists with neuroprotective properties. (1989)

Four diarylguanidine derivatives were synthesized. These compounds were found to displace, at submicromolar concentrations, 3H-labeled 1-[1-(2-thienyl)cyclohexyl]piperidine and (+)-[3H]MK-801 from phencyclidine receptors in brain membrane preparations. In electrophysiological experiments the diarylguanidines blocked N-methyl-D-aspartate (NMDA)-activated ion channels. These diarylguanidines also protected rat hippocampal neurons in vitro from glutamate-induced cell death. Our results show that some diarylguanidines are noncompetitive antagonists of NMDA receptor-mediated responses and have the neuroprotective property that is commonly associated with blockers of the NMDA receptor-gated cation channel. Diarylguanidines are structurally unrelated to known blockers of NMDA channels and, therefore, represent a new compound series for the development of neuroprotective agents with therapeutic value in patients suffering from stroke, from brain or spinal cord trauma, from hypoglycemia, and possibly from brain ischemia due to heart attack.
Differentiation of Mouse Embryonic Stem Cells into Blood (2008)

Embryonic stem (ES) cells can be maintained as pluripotent stem cells or induced to differentiate into many different somatic cell types. As ES-derived somatic cells can potentially be used for cell transplantation or cell-based therapy, ES cells have gained much scientific and general public attention. Successful derivation of blood from ES cells for tissue engineering will require a comprehensive understanding of inductive signals and downstream effectors involved in blood lineage development. Ideally, directed differentiation of ES cells into blood and isolation of pure hematopoietic progenitors will enhance our ability to utilize ES-derived blood cells for future clinical applications. The protocols provided in this unit describe methods of maintaining and differentiating mouse ES cells as well as identifying and isolating hematopoietic progenitors by utilizing flow cytometry and progenitor assays.
Improving Multi-Step Prediction of Learned Time Series Models (2015)

Most typical statistical and machine learning approaches to time series modeling optimize a single-step prediction error. In multiple-step simulation, the learned model is iteratively applied, feeding through the previous output as its new input. Any such predictor however, inevitably introduces errors, and these compounding errors change the input distribution for future prediction steps, breaking the train-test i.i.d assumption common in supervised learning. We present an approach that reuses training data to make a no-regret learner robust to errors made during multi-step prediction. Our insight is to formulate the problem as imitation learning; the training data serves as a "demonstrator" by providing corrections for the errors made during multi-step prediction. By this reduction of multi-step time series prediction to imitation learning, we establish theoretically a strong performance guarantee on the relation between training error and the multi-step prediction error. We present experimental results of our method, DaD, and show significant improvement over the traditional approach in two notably different domains, dynamic system modeling and video texture prediction.
Streaming QSplat: a viewer for networked visualization of large, dense models (2001)

Article Share on Streaming QSplat: a viewer for networked visualization of large, dense models Authors: Szymon Rusinkiewicz Stanford Univ., Stanford, CA Stanford Univ., Stanford, CAView Profile , Marc Levoy Stanford Univ., Stanford, CA Stanford Univ., Stanford, CAView Profile Authors Info & Claims I3D '01: Proceedings of the 2001 symposium on Interactive 3D graphicsMarch 2001 Pages 63–68https://doi.org/10.1145/364338.364350Online:01 March 2001Publication History 77citation679DownloadsMetricsTotal Citations77Total Downloads679Last 12 Months10Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Role of signal peptides in targeting of proteins in cyanobacteria (1994)

Proteins of cyanobacteria may be transported across one of two membrane systems: the typical eubacterial cell envelope (consisting of an inner membrane, periplasmic space, and an outer membrane) and the photosynthetic thylakoids. To investigate the role of signal peptides in targeting in cyanobacteria, Synechococcus sp. strain PCC 7942 was transformed with vectors carrying the chloramphenicol acetyltransferase reporter gene fused to coding sequences for one of four different signal peptides. These included signal peptides of two proteins of periplasmic space origin (one from Escherichia coli and the other from Synechococcus sp. strain PCC 7942) and two other signal peptides of proteins located in the thylakoid lumen (one from a cyanobacterium and the other from a higher plant). The location of the gene fusion products expressed in Synechococcus sp. strain PCC 7942 was determined by a chloramphenicol acetyltransferase enzyme-linked immunosorbent assay of subcellular fractions. The distribution pattern for gene fusions with periplasmic signal peptides was different from that of gene fusions with thylakoid lumen signal peptides. Primary sequence analysis revealed conserved features in the thylakoid lumen signal peptides that were absent from the periplasmic signal peptides. These results suggest the importance of the signal peptide in protein targeting in cyanobacteria and point to the presence of signal peptide features conserved between chloroplasts and cyanobacteria for targeting of proteins to the thylakoid lumen.
HLA-A*0201-Restricted T Cells from Humanized NOD Mice Recognize Autoantigens of Potential Clinical Relevance to Type 1 Diabetes (2006)

In both humans and NOD mice, particular MHC genes are primary contributors to development of the autoreactive CD4+ and CD8+ T cell responses against pancreatic beta cells that cause type 1 diabetes (T1D). Association studies have suggested, but not proved, that the HLA-A*0201 MHC class I variant is an important contributor to T1D in humans. In this study, we show that transgenic expression in NOD mice of HLA-A*0201, in the absence of murine class I MHC molecules, is sufficient to mediate autoreactive CD8+ T cell responses contributing to T1D development. CD8+ T cells from the transgenic mice are cytotoxic to murine and human HLA-A*0201-positive islet cells. Hence, the murine and human islets must present one or more peptides in common. Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is one of several important T1D autoantigens in standard NOD mice. Three IGRP-derived peptides were identified as targets of diabetogenic HLA-A*0201-restricted T cells in our NOD transgenic stock. Collectively, these results indicate the utility of humanized HLA-A*0201-expressing NOD mice in the identification of T cells and autoantigens of potential relevance to human T1D. In particular, the identified antigenic peptides represent promising tools to explore the potential importance of IGRP in the development of human T1D.
Graded Doping for Enhanced Colloidal Quantum Dot Photovoltaics (2013)

A novel approach to improving all-inorganic colloidal quantum dot (CQD) homojunction solar cells by engineering the doping spatial profile to produce a doping gradient within the n-type absorber is presented. The doping gradient greatly improves carrier collection and enhances the voltages attainable by the device, leading to a 1 power point power conversion efficiency (PCE) improvement over previous inorganic CQD solar cells.
Indoor Positioning System Using Magnetic Field Map Navigation and an Encoder System (2017)

In the indoor environment, variation of the magnetic field is caused by building structures, and magnetic field map navigation is based on this feature. In order to estimate position using this navigation, a three-axis magnetic field must be measured at every point to build a magnetic field map. After the magnetic field map is obtained, the position of the mobile robot can be estimated with a likelihood function whereby the measured magnetic field data and the magnetic field map are used. However, if only magnetic field map navigation is used, the estimated position can have large errors. In order to improve performance, we propose a particle filter system that integrates magnetic field map navigation and an encoder system. In this paper, multiple magnetic sensors and three magnetic field maps (a horizontal intensity map, a vertical intensity map, and a direction information map) are used to update the weights of particles. As a result, the proposed system estimates the position and orientation of a mobile robot more accurately than previous systems. Also, when the number of magnetic sensors increases, this paper shows that system performance improves. Finally, experiment results are shown from the proposed system that was implemented and evaluated.
Anti-Tumor Activity of a Novel Compound-CDF Is Mediated by Regulating miR-21, miR-200, and PTEN in Pancreatic Cancer (2011)

These results strongly suggest that the anti-tumor activity of CDF is associated with inhibition of CSC function via down-regulation of CSC-associated signaling pathways. Therefore, CDF could be useful for the prevention of tumor recurrence and/or treatment of PC with better treatment outcome in the future.
β-Glucuronidase of Rat Liver Lysosomes (1971)

Abstract Previous work has established that rat liver contains several closely related forms of β-glucuronidase differing in their subcellular distribution. The present report focuses on the most abundant form, which is the major one occurring in lysosomes. This β-glucuronidase was purified 8,400-fold, to the highest specific activity thus far reported. The preparation is homogeneous by all criteria applied. It contains a relatively high content of glutamic and aspartic acids and a very low content of sulfur-containing amino acids. The enzyme has a molecular weight of approximately 280,000, the value obtained depending upon the method used for the determination. Since gel filtration in the presence of urea, or polyacrylamide gel electrophoresis under denaturing conditions, yielded results suggesting that the enzyme consists of subunits of molecular weight of approximately 75,000, the native enzyme apparently is a tetramer.
Error Monitoring Using External Feedback: Specific Roles of the Habenular Complex, the Reward System, and the Cingulate Motor Area Revealed by Functional Magnetic Resonance Imaging (2003)

The dopaminergic system has been shown to be involved in the processing of rewarding stimuli, specifically of errors in reward prediction, in animal studies as well as in recent neuroimaging studies in humans. Furthermore, a specific role of dopamine in the human homolog of the rostral cingulate motor area (rCMA) was proposed in a recent model of error detection. Negative feedback as well as self-detected errors elicit a negative event-related brain potential probably generated in the rCMA. We performed two experiments using functional magnetic resonance imaging to investigate the brain activity related to negative and positive feedback in a dynamically adaptive motion prediction task. Whereas positive feedback raised hemodynamic activity in the ventral striatum (nucleus accumbens), negative feedback activated the rCMA, the inferior anterior insula, and the epithalamus (habenular complex). These data demonstrate the role of the habenular complex in the control of the human reward system, a function previously hypothesized on the basis of animal research. The rCMA reacted only to errors with negative feedback but not to errors without feedback, which ruled out an influence of response conflict or uncertainty on its role in error detection by external signals.
Analysis of Photo-initiators in Visible-light-cured Dental Composite Resins (1988)

Seven commercial visible-light-cured (VL) dental composite resins were analytically studied for identification of the photo-initiator consisting of photo-sensitizer and reducing agent. Gas-liquid chromatography (GC) was used for the determination of the dilute components extracted from the composite resin. Mass spectroscopy (GC-MS) was used for confirmation of the qualitative data obtained by GC. The results showed that all composite resins examined included camphorquinone (CQ) as a photo-sensitizer. The concentration of CQ in the resin phase, however, ranged from 0.17 to 1.03% w/w. The composite resin with hybrid-sized filler tended to have a higher concentration of CQ than did the micro-filled composite resin. As for the reducing agent, two out of seven brands contained dimethylaminoethyl methacrylate (DMAEMA), and one included dimethyl-p-toluidine (DMPTI). The mixing ratio between CQ and the amine in these three composite resins also varied. Another four brands did not contain either DMAEMA or DMPTI, and would utilize different reducing agents.
Computer Aided Structural Analysis of Axle Tilting Effect on Tractor Front Axle Support (2014)

Studies were carried out to determine the worst load case scenario on Ursus 3512 60hp Tractor Front Axle Support using MATLAB to analyze 36 load cases. The worst load case scenario was found to be the dynamic load case of 3g with wheel force of 9810N and axle angle of 12 0 .The load on the Pivot hole of the tractor support was found to be 56057N. The component was modelled using Pro-Engineer (now CREO Elements). The structural analysis of component was done with the worst load case using Pro-Mechanica. The working or design stress was generated from the analysis within best convergence limit. The estimated maximum limiting yield stress estimated as von Mises stress of the front axle support is 88 N/mm 2 . The factor of safety for the component design was calculated to be 2.84 which were lower than the recommended value of 5.5 to 6.5. The Minimum allowable stress and Maximum allowable stress for the Component design would be 484N/mm 2 and 572N/mm 2 .
Metalloproteinase inhibitors: biological actions and therapeutic opportunities (2002)

Tissue inhibitors of metalloproteinases (TIMPs) are the major cellular inhibitors of the matrix metalloproteinase (MMP) sub-family, exhibiting varying efficacy against different members, as well as different tissue expression patterns and modes of regulation. Other proteins have modest inhibitory activity against some of the MMPs, including domains of netrins, the procollagen C-terminal proteinase enhancer (PCPE), the reversion-inducing cysteine-rich protein with Kazal motifs (RECK), and tissue factor pathway inhibitor (TFPI-2), but their physiological significance is not at all clear. Alpha2-macroglobulin, thrombospondin-1 and thrombospondin-2 can bind to some MMPs and act as agents for their removal from the extracellular environment. In contrast, few effective inhibitors of other members of the metzincin family, the astacins or the distintegrin metalloproteinases, ADAMs have been identified. Many of these MMP inhibitors, including the TIMPs, possess other biological activities which may not be related to their inhibitory capacities. These need to be thoroughly characterized in order to allow informed development of MMP inhibitors as potential therapeutic agents. Over activity of MMPs has been implicated in many diseases, including those of the cardiovascular system, arthritis and cancer. The development of synthetic small molecule inhibitors has been actively pursued for some time, but the concept of the use of the natural inhibitors, such as the TIMPs, in gene based therapies is being assessed in animal models and should provide useful insights into the cell biology of degradative diseases.