gebhart/patrepeval huggingface dataset:
The post‐natal heart contains a myocardial stem cell population (2002)

The recent identification of stem cell pools in a variety of unexpected tissue sources has raised the possibility that a pluripotent stem cell population may reside in the myocardium and contribute to the post-natal growth of this tissue. Here, we demonstrate that the post-natal myocardium contains a resident verapamil-sensitive side population (SP), with stem cell-like activity. When growth of the post-natal heart was attenuated through over-expression of a dominant negative cardiac transcription factor (MEF2C), the resident SP cell population was subject to activation, followed by a consequent depletion. In addition, cardiac SP cells are capable of fusion with other cell types, but do not adopt the corresponding gene expression profile. These observations suggest that a responsive stem cell pool resides in the adult myocardium, and may influence adaptation of the post-natal heart.
Engineering Biosensors by Introducing Fluorescent Allosteric Signal Transducers:  Construction of a Novel Glucose Sensor (1998)

The development of biosensors based on genetically engineered proteins offers many potential advantages to sensors that rely on natural proteins only. Here we present how protein engineering techniques can be used to integrate optical signal transduction functions directly into proteins by incorporating environmentally sensitive fluorescent groups that are allosterically linked to a ligand binding site, using a structure-based rational design approach. The location of potential fluorescent allosteric signal transduction (FAST) sites were predicted in the periplasmic Glucose Binding Protein of Escherichia coli. Single cysteine mutations were constructed at these locations, which allowed site-specific, covalent coupling of environmentally sensitive fluorophores. The fluorescence of these conjugates was shown to be hyperbolically dependent upon glucose concentration, indicating that the behavior of the fluorophore is allosterically coupled to the degree of occupancy at the glucose binding site, as predicted. Glucose Binding Proteins with engineered FAST functions may allow the development of a new class of optical glucose sensors.
Perfect spatial hashing (2006)

We explore using hashing to pack sparse data into a compact table while retaining efficient random access. Specifically, we design a perfect multidimensional hash function -- one that is precomputed on static data to have no hash collisions. Because our hash function makes a single reference to a small offset table, queries always involve exactly two memory accesses and are thus ideally suited for parallel SIMD evaluation on graphics hardware. Whereas prior hashing work strives for pseudorandom mappings, we instead design the hash function to preserve spatial coherence and thereby improve runtime locality of reference. We demonstrate numerous graphics applications including vector images, texture sprites, alpha channel compression, 3D-parameterized textures, 3D painting, simulation, and collision detection.
ALKFusions in a Wide Variety of Tumor Types Respond to Anti-ALK Targeted Therapy (2017)

Rearrangements involving the <i>ALK</i> gene have been detected in dozens of cancer types using next-generation sequencing. Patients whose tumors harbor <i>ALK</i> rearrangements or fusions respond to treatment with crizotinib and alectinib, including tumors not normally associated with <i>ALK</i> mutations, such as non-Langerhans cell histiocytosis or renal cell carcinoma. Comprehensive genomic profiling using next-generation sequencing can detect targetable <i>ALK</i> fusions irrespective of tumor type or fusions partner.
The UVA/PADOVA Type 1 Diabetes Simulator (2014)

Recent studies have provided new insights into nonlinearities of insulin action in the hypoglycemic range and into glucagon kinetics as it relates to response to hypoglycemia. Based on these data, we developed a new version of the UVA/PADOVA Type 1 Diabetes Simulator, which was submitted to FDA in 2013 (S2013). The model of glucose kinetics in hypoglycemia has been improved, implementing the notion that insulin-dependent utilization increases nonlinearly when glucose decreases below a certain threshold. In addition, glucagon kinetics and secretion and action models have been incorporated into the simulator: glucagon kinetics is a single compartment; glucagon secretion is controlled by plasma insulin, plasma glucose below a certain threshold, and glucose rate of change; and plasma glucagon stimulates with some delay endogenous glucose production. A refined statistical strategy for virtual patient generation has been adopted as well. Finally, new rules for determining insulin to carbs ratio (CR) and correction factor (CF) of the virtual patients have been implemented to better comply with clinical definitions. S2013 shows a better performance in describing hypoglycemic events. In addition, the new virtual subjects span well the real type 1 diabetes mellitus population as demonstrated by good agreement between real and simulated distribution of patient-specific parameters, such as CR and CF. S2013 provides a more reliable framework for in silico trials, for testing glucose sensors and insulin augmented pump prediction methods, and for closed-loop single/dual hormone controller design, testing, and validation.
Disruption of Cortical Actin in Skeletal Muscle Demonstrates an Essential Role of the Cytoskeleton in Glucose Transporter 4 Translocation in Insulin-sensitive Tissues (2004)

Cell culture work suggests that signaling to polymerize cortical filamentous actin (F-actin) represents a required pathway for the optimal redistribution of the insulin-responsive glucose transporter, GLUT4, to the plasma membrane. Recent in vitro study further suggests that the actin-regulatory neural Wiskott-Aldrich syndrome protein (N-WASP) mediates the effect of insulin on the actin filament network. Here we tested whether similar cytoskeletal mechanics are essential for insulin-regulated glucose transport in isolated rat epitrochlearis skeletal muscle. Microscopic analysis revealed that cortical F-actin is markedly diminished in muscle exposed to latrunculin B. Depolymerization of cortical F-actin with latrunculin B caused a time- and concentration-dependent decline in 2-deoxyglucose transport. The loss of cortical F-actin and glucose transport was paralleled by a decline in insulin-stimulated GLUT4 translocation, as assessed by photolabeling of cell surface GLUT4 with Bio-LC-ATB-BMPA. Although latrunculin B impaired insulin-stimulated GLUT4 translocation and glucose transport, activation of phosphatidylinositol 3-kinase and Akt by insulin was not rendered ineffective. In contrast, the ability of insulin to elicit the cortical F-actin localization of N-WASP was abrogated. These data provide the first evidence that actin cytoskeletal mechanics are an essential feature of the glucose transport process in intact skeletal muscle. Furthermore, these findings support a distal actin-based role for N-WASP in insulin action in vivo.
The Associations between VEGF Gene Polymorphisms and Diabetic Retinopathy Susceptibility: A Meta-Analysis of 11 Case-Control Studies (2014)

AIMS. Published data on the associations of VEGF polymorphisms with diabetic retinopathy (DR) susceptibility are inconclusive. A systematic meta-analysis was undertaken to clarify this topic. METHODS. Data were collected from the following electronic databases: PubMed, Embase, OVID, Web of Science, Elsevier Science Direct, Excerpta Medica Database (EMBASE), and Cochrane Library with the last report up to January 10, 2014. ORs and 95% CIs were calculated for VEGF-2578C/A (rs699947), -1154G/A (rs1570360), -460T/C (rs833061), -634G>C (rs2010963), and +936C/T (rs3025039) in at least two published studies. Meta-analysis was performed in a fixed/random effect model by using the software STATA 12.0. RESULTS. A total of 11 studies fulfilling the inclusion criteria were included in this meta-analysis. A significant relationship between VEGF+936C/T (rs3025039) polymorphism and DR was found in a recessive model (OR = 3.19, 95% CI = 1.20-8.41, and P(z) = 0.01) in Asian and overall populations, while a significant association was also found between -460T/C (rs833061) polymorphism and DR risk under a recessive model (OR = 2.12, 95% CI = 1.12-4.01, and P(z) = 0.02). CONCLUSIONS. Our meta-analysis demonstrates that +936C/T (rs3025039) is likely to be associated with susceptibility to DR in Asian populations, and the recessive model of -460T/C (rs833061) is associated with elevated DR susceptibility.
Magnetic Permeability Measurements in Bioanalysis and Biosensors (1996)

A new transducer concept in bioanalysis and biosensors, utilizing measurements of magnetic permeability, is reported. A model system based on dextran ferrofluid, concanavalin A immobilized to a carrier (Sepharose), and glucose was used to demonstrate the feasibility of this approach. Direct ferromagnetic detection of the dextran ferrofluid was achieved by using a measuring coil (transducer) in a Maxwell bridge. A sensitivity of 21 μV/(μg Fe/mL) and a rsd value of 3.8% were obtained (n = 5). It was also demonstrated that a small, non-ferromagnetic metabolite (glucose) could be detected using a competitive approach. With an increasing concentration of glucose (20-40 mM), we observed a decrease in the response (0.59-0.11 mV). Reference measurements performed on Sepharose without the biorecognition element, concanavalin A, showed no significant response (0.01 mV). Some potential advantages and drawbacks of this novel type of magnetic transducer are discussed. The advantages include very low interference from the sample matrix, as the transducer is only sensitive to ferromagnetic substances, which rarely are present in samples. In addition, it is suggested that these transducers should be free from fouling. The new transducers are proposed to provide the basis for a new group of affinity biosensors suitable for in vivo and in vitro use.
El self como una estructura relacional: Un diálogo con la teoría del self múltiple (2003)

Este artículo encara la crítica postmoderna a las teorías del self unificado, crítica que sostiene que el self no es algo unificado sino múltiple, no es una entidad estática sino que fluctúa constantemente, no es un centro de iniciativa aislado sino constituido intersubjetivamente. El autor propone que existen dos tipos de división en la experiencia del self: las divisiones disociativas de la teoría del self múltiple y otra división, similar a las divisiones entre las agencias estructurales de Freud, entre lo que se denomina aquí el ¿self intersubjetivo¿ y la ¿experiencia subjetiva primaria¿. En contraste con los estados del self disociados, que tienen lugar en diferentes momentos a lo largo del tiempo, estas dos dimensiones de la experiencia del self se producen de forma simultánea; en realidad, lo más importante es la relación entre ellas. El autor sugiere que es esta relación intrapsíquica, tal como ocurre en un momento psicológico determinado, la que determina las cualidades de la experiencia del self que se enfatizan en las teorías del self unificado: cualidades tales como cohesión versus fragmentación; autenticidad vs. falsedad; vitalidad versus agotamiento; regulación del self óptima versus regulación no óptima; e iniciativa versus sentir que uno está a merced de los otros. Más aún, uno de los organizadores más importantes del self intersubjetivo son las identificaciones tempranas, especialmente las ¿identificaciones con la respuesta del otro al self¿. Se discuten las implicaciones de estos conceptos para la acción terapéutica y se ilustran con una extensa exposición de un caso analítico.
Conformationally Locked Nucleoside Analogs. Synthesis of Dideoxycarbocyclic Nucleoside Analogs Structurally Related to Neplanocin C (1994)

The glycon moiety of nucleosides in solution is known to exist in a rapid dynamic equilibrium between extreme northern and southern conformations as defined by the pseudorotation cycle. The concept of preparing rigid nucleoside analogues with the glycon conformation locked in one of these two extremes was tested with the synthesis of some cyclopropane-fused dideoxycarbocyclic nucleosides, similar to the well-known class of anti-HIV active dideoxynucleosides. The new compounds described here are dideoxynucleoside analogues of the fermentation product neplanocin C (6) which exhibits a typical northern geometry for its 6-oxabicyclo[3.1.0]hexane pseudosugar moiety. However, in view of the lability of the epoxide ring in this system, the equivalent cyclopropane-fused bicyclo[3.1.0]hexane system was used instead to prepare the corresponding dideoxynucleoside analogues bearing all the common bases [(+/-)-9-13]. Due to the well-documented preference of unrestricted bicyclo[3.1.0]hexane systems to exist exclusively in a boat conformation, the resulting nucleosides are structurally locked in a typical northern conformation similar to that of neplanocin C. The locked northern conformation in these nucleosides remained unchanged in solution in the 20-80 degrees C temperature range according to variable temperature 1H NMR studies. For the synthesis of these compounds, racemic trans-1-[(benzyloxy)methyl]-4-hydroxybicyclo[3.1.0]hexane [(+/-)-18] was prepared by a samarium-promoted cyclopropanation reaction with the antecedent cyclopentenol. All of the bases were incorporated under Mitsunobu conditions and converted to the desired final products following a standard methodology. Anti-HIV evaluation revealed that only the adenosine analogue (+/-)-9 possessed enough activity to warrant resolution into its optical antipodes. This was realized by chiral HPLC chromatography to give the individual enantiomers (-)-32 and (+)-33. Adenosine deaminase was used to identify isomer (+)-33 as the enantiomer with the "natural" configuration which was solely responsible for the observed biological activity and toxicity of (+/-)-9. It is possible that the exclusive northern conformation adopted by these nucleosides reduces their substrate affinity for the various activating kinases, except in the case of the adenosine analogue.
Two New Tryptophan-Derived Alkaloids from the Okinawan Marine Sponge Aplysina Sp. (1994)

Two new indole alkaloids, isoplysin A [2] and D-6-bromohypaphorine [3], have been isolated from the Okinawan marine sponge Aplysina sp. and their structures were elucidated by spectral and chemical means.
Single-Channel Multi-Speaker Separation Using Deep Clustering (2016)

Deep clustering is a recently introduced deep learning architecture that uses discriminatively trained embeddings as the basis for clustering. It was recently applied to spectrogram segmentation, resulting in impressive results on speaker-independent multi-speaker separation. In this paper we extend the baseline system with an end-to-end signal approximation objective that greatly improves performance on a challenging speech separation. We first significantly improve upon the baseline system performance by incorporating better regularization, larger temporal context, and a deeper architecture, culminating in an overall improvement in signal to distortion ratio (SDR) of 10.3 dB compared to the baseline of 6.0 dB for two-speaker separation, as well as a 7.1 dB SDR improvement for three-speaker separation. We then extend the model to incorporate an enhancement layer to refine the signal estimates, and perform end-to-end training through both the clustering and enhancement stages to maximize signal fidelity. We evaluate the results using automatic speech recognition. The new signal approximation objective, combined with end-to-end training, produces unprecedented performance, reducing the word error rate (WER) from 89.1% down to 30.8%. This represents a major advancement towards solving the cocktail party problem.
Fully-depleted FBC (floating body cell) with enlarged signal window and excellent logic process compatibility (2005)

Fully-depleted (FD) floating body cell on 55nm SOI featuring excellent logic process compatibility has been successfully developed. For the first time FD operation is reported through significant signal enlargement by negative substrate bias. Using standard salicide process and FD operation, high-density embedded memory on SOI is achievable.
Magic Angle Spinning NMR Structure Determination of Proteins from Pseudocontact Shifts (2013)

Magic angle spinning solid-state NMR is a unique technique to study atomic-resolution structure of biomacromolecules which resist crystallization or are too large to study by solution NMR techniques. However, difficulties in obtaining sufficient number of long-range distance restraints using dipolar coupling based spectra hamper the process of structure determination of proteins in solid-state NMR. In this study it is shown that high-resolution structure of proteins in solid phase can be determined without the use of traditional dipolar-dipolar coupling based distance restraints by combining the measurements of pseudocontact shifts (PCSs) with Rosetta calculations. The PCSs were generated by chelating exogenous paramagnetic metal ions to a tag 4-mercaptomethyl-dipicolinic acid, which is covalently attached to different residue sites in a 56-residue immunoglobulin-binding domain of protein G (GB1). The long-range structural restraints with metal-nucleus distance of up to ∼20 Å are quantitatively extracted from experimentally observed PCSs, and these are in good agreement with the distances back-calculated using an X-ray structure model. Moreover, we demonstrate that using several paramagnetic ions with varied paramagnetic susceptibilities as well as the introduction of paramagnetic labels at different sites can dramatically increase the number of long-range restraints and cover different regions of the protein. The structure generated from solid-state NMR PCSs restraints combined with Rosetta calculations has 0.7 Å root-mean-square deviation relative to X-ray structure.
Oral immunization with a replication-deficient recombinant vaccinia virus protects mice against influenza (1996)

Mice immunized with two intragastrically administered doses of a replication-deficient recombinant vaccinia virus containing the hemagglutinin and nucleoprotein genes from H1N1 influenza virus developed serum anti-H1 immunoglobulin G (IgG) antibody that completely protected the lungs from challenge with H1N1. Almost all of the mice given two intragastric doses also developed mucosal anti-H1 IgA antibody, and those with high anti-H1 IgA titers had completely protected noses. Intramuscular injection of the vaccine protected the lungs but not the noses from challenge. We also found that the vaccine enhanced recovery from infection caused by a shifted (H3N2) influenza virus, probably through the induction of nucleoprotein-specific cytotoxic T-lymphocyte activity. A replication-deficient, orally administered, enteric-coated, vaccinia virus-vectored vaccine might safely protect humans against influenza.
Moisture measurement in free flowing particulate solids using an off-the-shelf capacitance level probe (1999)

A proprietary level probe which responds to changes in the di-electric properties of the medium surrounding it has been used to measure the moisture content of a powdered dairy product. The in situ bulk density of the test material was also significant. The moisture content of the test material was varied by changing the drying time in a laboratory oven, and bulk density was altered by controlled mechanical tapping of the test cell. A simple empirical model which includes the bulk density of the test material has been used to correlate the experimental results. Factory trials confirmed the feasibility of using a level probe as an in-line moisture sensor.
A Layer-To-Layer Model and Feedback Control of Ink-Jet 3-D Printing (2014)

Ink-jet 3-D printing is a promising additive manufacturing technology with the potential for impacting a wide variety of industries. In typical ink-jet 3-D printing, the part is built up by depositing droplets layer upon layer in an open-loop manner, while curing each layer after it is deposited. Droplet and edge dimensions are typically predicted through extensive experimentation and are assumed to remain constant throughout the printing process. However, there is no guarantee of the consistent droplet shape and dimensions or the smoothness of the finished parts due to the inherent uncertainty in the process. To address this issue, we propose a model-based feedback control law for ink-jet 3-D printing that uses a height sensor for measuring profile height after each layer for determining the appropriate layer patterns for subsequent layers. Toward this goal, a model describing the relationship between height profile change and droplet deposition in the layer building process is first proposed and experimentally identified. Based on this model, a closed-loop layer-to-layer control algorithm is then developed for the ink-jet printing process. The proposed algorithm uses a model predictive control algorithm to minimize the difference between the predicted height and the desired height and the predicted surface unevenness after a fixed number of layers. We also present an extension of the algorithm for two-material printing, which can enable printing of complex 3-D geometry (by using a support material for overhang). Experimental and simulation results show that the algorithm is able to achieve more consistent shapes between layers, reduced edge shrinking of the part, and a smoother top layer surface.
Effects of 4-Aminopyridine on Motor Evoked Potentials in Patients with Spinal Cord Injury (1997)

The potassium (K+) channel-blocking agent 4-aminopyridine (4-AP) is currently being investigated for its potential therapeutic value in patients with spinal cord injury (SCI). The present study was designed to test the hypothesis that 4-AP ameliorates central motor conduction deficits in individuals with SCI. Oral 4-AP (10 mg) was administered to 19 (n = 19) SCI subjects with stable neurological deficits. Their response to the drug was monitored using motor evoked potentials (MEPs) following transcranial magnetic stimulation of motor cortex and various measures of segmental or peripheral reflex activity (F-waves, H-reflex, and M-response) recorded from lower limb muscles. The mean MEP amplitude in the extensor digitorum brevis muscle (left) was significantly (p < .05) increased from x = .25 +/- .42 mV to x = .59 +/- 1.04 mV at 2 h after drug administration, and the cortical stimulation threshold was reduced (p < .05) by 5.8%. Similar results were obtained in all subjects exhibiting MEPs (n = 13) and in all muscles (n = 6) studied. These changes were maintained at 4 h postdrug. MEP latencies were reduced in all subjects who initially exhibited abnormally prolonged MEP latencies relative to control group (n = 13) values. F-wave, H-reflex, and M-response values (latency and amplitude) were not systematically altered by 4-AP, leading to the conclusion that it was central motor conduction that was enhanced. This interpretation was supported by observed reductions in central motor conduction time (CMCT) in the majority of SCI subjects from whom CMCT measurements were obtained, two of whom anecdotally reported improved motor control after 4-AP, and by increased MEP:M-wave amplitude ratios. The MEP:M-wave ratios indicated that the magnitude of the effect of 4-AP on motoneuron recruitment was not large, in absolute terms (<4% motoneuron pool), but was appreciable relative to the initial level of motoneuron recruitment. These results provide the first statistically significant, objective evidence of improved functioning of the neuromuscular system in chronically injured SCI subjects receiving 4-AP and suggest that the improvements are mediated through enhanced central conduction. The results further support the emerging view that pharmaceutical management of central conduction deficits may prove to be a useful therapeutic strategy for some patients with long-standing SCI.