gebhart/patrepeval huggingface dataset:
Developmentally Regulated Switch in Alternatively Spliced SNAP-25 Isoforms Alters Facilitation of Synaptic Transmission (2004)

Although the basic molecular components that promote regulated neurotransmitter release are well established, the contribution of these proteins as regulators of the plasticity of neurotransmission and refinement of synaptic connectivity during development is elaborated less fully. For example, during the period of synaptic growth and maturation in brain, the expression of synaptosomal protein 25 kDa (SNAP-25), a neuronal t-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) essential for action potential-dependent neuroexocytosis, is altered through alternative splicing of pre-mRNA transcripts. We addressed the role of the two splice-variant isoforms of SNAP-25 with a targeted mouse mutation that impairs the shift from SNAP-25a to SNAP-25b. Most of these mutant mice die between 3 and 5 weeks of age, which coincides with the time when SNAP-25b expression normally reaches mature levels in brain and synapse formation is essentially completed. The altered expression of these SNAP-25 isoforms influences short-term synaptic function by affecting facilitation but not the initial probability of release. This suggests that mechanisms controlling alternative splicing between SNAP-25 isoforms contribute to a molecular switch important for survival that helps to guide the transition from immature to mature synaptic connections, as well as synapse regrowth and remodeling after neural injury.
Segmentation using eigenvectors: a unifying view (1999)

Automatic grouping and segmentation of images remains a challenging problem in computer vision. Recently, a number of authors have demonstrated good performance on this task using methods that are based on eigenvectors of the affinity matrix. These approaches are extremely attractive in that they are based on simple eigendecomposition algorithms whose stability is well understood. Nevertheless, the use of eigendecompositions in the context of segmentation is far from well understood. In this paper we give a unified treatment of these algorithms, and show the close connections between them while highlighting their distinguishing features. We then prove results on eigenvectors of block matrices that allow us to analyze the performance of these algorithms in simple grouping settings. Finally, we use our analysis to motivate a variation on the existing methods that combines aspects from different eigenvector segmentation algorithms. We illustrate our analysis with results on real and synthetic images.
Structure-Function Based Design of Small Molecule Inhibitors Targeting Rho Family GTPases (2006)

Rho GTPases of the Ras superfamily are involved in the regulation of multiple cell functions and have been implicated in the pathology of various human diseases including cancer. They are attractive drug targets in future targeted therapy. A wealth of structure-function information made available by high resolution structures and mutagenesis studies has laid out the foundation for the derivation of a mechanism-based targeting strategy. Here we describe the rational design and characterizations of a first generation Rac-specific small molecule inhibitor. Based on the structure-function information of Rac interaction with GEFs, in a computer based Virtual Screening we have identified NSC23766, a highly soluble and membrane permeable compound, as a specific inhibitor of a subset of GEF binding to Rac and therefore Rac activation. In fibroblast cells NSC23766 inhibited Rac1 GTP-loading without affecting Cdc42 or RhoA activity and suppressed the Rac-GEF, Tiam1, and oncogenic Ras induced cell growth and transformation. NSC23766 also potently inhibited the prostate PC-3 cancer cell proliferation and invasion induced by Rac hyperactivation. Intraperitoneal administration of NSC23766 to laboratory mice resulted in effective Rac GTPase suppression and hematopoietic stem cell mobilization from the bone marrow to the peripheral blood, similar to the effects of genetically targeted disruption of Rac GTPases in the animals. A co-crystal structure of NSC23766 bound to Rac1 provided further insight for future medicinal chemistry modification and improvement of this lead Rac-specific inhibitor. Thus, structure-function based rational design may represent a new avenue for generating lead small molecule inhibitors of Ras superfamily GTPases that are useful for modulating pathological conditions in which the small GTPase deregulation may play a role.
The autonomous micro robot "Alice": a platform for scientific and commercial applications (2002)

Over the last years various mobile micro robots have been developed at different labs for research issues. Most of them have remarkable features but are handmade prototypes not suitable for large-scale production. This paper presents a micro robot design where major efforts have been undertaken in order to reduce costs and facilitate serial production, while improving the performances of the robot. The newly designed robot consists of only three major parts, the flexible print with the electronics and the two motors directly mounted on it, the plastic frame on which the print is attached by four screws and the battery. Thanks to its very low costs, the micro robot is of high interest for multiple robot applications, for investigation of collective behavior and for the toy market. Our robot Alice with a size about 2/spl times/2/spl times/2 cm, has a ultra low power consumption allowing autonomy up to 10 hours, and has a modular concept for programming and hardware extension. This makes it very useful for research and future developments. We extended the robot's abilities with 4 distance sensors, an infrared communication module and a radio communication module. By only modifying the software, many additional functions are available. Some of them are presented such as obstacle avoidance, wall following, remote inspection and guidance, communication between robots and multi-robot exploration.
Regioselective alkylation of phenoxy-substituted 3-(methylthio)indolin-2(3H)-ones. Preparation of 3-, 1,3-, and 1,3,3-substituted indolin-2(3H)-ones (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRegioselective alkylation of phenoxy-substituted 3-(methylthio)indolin-2(3H)-ones. Preparation of 3-, 1,3-, and 1,3,3-substituted indolin-2(3H)-onesGary M. KarpCite this: J. Org. Chem. 1992, 57, 17, 4765–4772Publication Date (Print):August 1, 1992Publication History Published online1 May 2002Published inissue 1 August 1992https://pubs.acs.org/doi/10.1021/jo00043a044https://doi.org/10.1021/jo00043a044research-articleACS PublicationsRequest reuse permissionsArticle Views357Altmetric-Citations19LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Hydrolysis of platelet-activating factor by human serum paraoxonase (2001)

Human serum paraoxonase (human PON1) has been shown to be important in the metabolism of phospholipid and cholesteryl ester hydroperoxides, thereby preventing the oxidation of low-density lipoprotein (LDL) and retarding atherogenesis. However, the exact substrate specificity of PON1 has not been established. In the present study we show that purified PON1 hydrolyses platelet-activating factor (PAF). We could find no evidence for contamination of our preparation with authentic platelet-activating-factor acetylhydrolase (PAFAH) by immunoblotting with a PAFAH monoclonal antibody or by sequencing the purified protein. In addition the specific PAFAH inhibitor SB-222657 did not affect the ability of PON1 to hydrolyse PAF (30.1±;2.8µmol/min per mg of protein with no inhibitor; 31.4±;2.2µmol/min per mg of protein with 100nM inhibitor) or phenyl acetate (242.6±;30.8 versus 240.8±;31.5µmol/min per mg of protein with and without inhibitor respectively). SB-222657 was also unable to inhibit PAF hydrolysis by isolated human high-density lipoprotein (HDL), but completely abolished the activity of human LDL. Ostrich (Struthio camelus) HDL, which does not contain PON1, was unable to hydrolyse PAF. These data provide evidence that PON1 may limit the action of this bioactive pro-inflammatory phospholipid.
The Effect of Alendronate Loaded Biphasic Calcium Phosphate Scaffolds on Bone Regeneration in a Rat Tibial Defect Model (2015)

This study investigated the effect of alendronate (Aln) released from biphasic calcium phosphate (BCP) scaffolds. We evaluated the in vitro osteogenic differentiation of Aln/BCP scaffolds using MG-63 cells and the in vivo bone regenerative capability of Aln/BCP scaffolds using a rat tibial defect model with radiography, micro-computed tomography (CT), and histological examination. In vitro studies included the surface morphology of BCP and Aln-loaded BCP scaffolds visualized using field-emission scanning electron microscope, release kinetics of Aln from BCP scaffolds, alkaline phosphatase (ALP) activity, calcium deposition, and gene expression. The in vitro studies showed that sustained release of Aln from the BCP scaffolds consisted of porous microstructures, and revealed that MG-63 cells cultured on Aln-loaded BCP scaffolds showed significantly increased ALP activity, calcium deposition, and gene expression compared to cells cultured on BCP scaffolds. The in vivo studies using radiograph and histology examination revealed abundant callus formation and bone maturation at the site in the Aln/BCP groups compared to the control group. However, solid bony bridge formation was not observed at plain radiographs until 8 weeks. Micro-CT analysis revealed that bone mineral density and bone formation volume were increased over time in an Aln concentration-dependent manner. These results suggested that Aln/BCP scaffolds have the potential for controlling the release of Aln and enhance bone formation and mineralization.
Androgens in Men — Uses and Abuses (1996)

The female steroid hormones, estrogen and progesterone, are prescribed widely by physicians, and their risks and benefits have been studied extensively. Although androgen preparations have been available for many years, most clinicians are less familiar with these hormones, and their risks and benefits have received less attention. The most common indication for androgen therapy is hypogonadism in men, but other potential uses of androgens are being explored. In addition, androgen abuse has become common among athletes and bodybuilders. It is therefore important that physicians be aware of the physiology, pharmacology, clinical indications, and adverse effects of androgens.PhysiologyThe hypothalamus . . .
Reclassification of Urinary Tract Infections in Critically Ill Trauma Patients: A Time-Dependent Analysis (2003)

Escherichia coli was the most common pathogen in all nosocomial infection categories. Increased age, gender, and obesity, in addition to catheter-days, were significant risk factors for UTI in trauma patients. Specific risk factors may predispose patients to pathogens that are not ordinarily covered by usually-chosen antibiotic therapy.
Scaling method for fast Monte Carlo simulation of diffuse reflectance spectra from multilayered turbid media (2007)

A scaling Monte Carlo method has been developed to calculate diffuse reflectance from multilayered media with a wide range of optical properties in the ultraviolet-visible wavelength range. This multilayered scaling method employs the photon trajectory information generated from a single baseline Monte Carlo simulation of a homogeneous medium to scale the exit distance and exit weight of photons for a new set of optical properties in the multilayered medium. The scaling method is particularly suited to simulating diffuse reflectance spectra or creating a Monte Carlo database to extract optical properties of layered media, both of which are demonstrated in this paper. Particularly, it was found that the root-mean-square error (RMSE) between scaled diffuse reflectance, for which the anisotropy factor and refractive index in the baseline simulation were, respectively, 0.9 and 1.338, and independently simulated diffuse reflectance was less than or equal to 5% for source-detector separations from 200 to 1500 microm when the anisotropy factor of the top layer in a two-layered epithelial tissue model was varied from 0.8 to 0.99; in contrast, the RMSE was always less than 5% for all separations (from 0 to 1500 microm) when the anisotropy factor of the bottom layer was varied from 0.7 to 0.99. When the refractive index of either layer in the two-layered tissue model was varied from 1.3 to 1.4, the RMSE was less than 10%. The scaling method can reduce computation time by more than 2 orders of magnitude compared with independent Monte Carlo simulations.
NEW YORK DERMATOLOGICAL SOCIETY (1948)

<h3>Urticaria Pigmentosa (Xanthelasmoidea). Presented by Dr. Fred Wise.</h3> D. F., a boy aged 6 weeks, exhibited the eruption shortly after birth. The family history is irrelevant, and the patient's general health appears to be unaffected. The eruption is universal, with predominance of the lesions on the torso and extremities. The entire body exhibits a distinct yellow color. The face is swollen; the eyelids are edematous and of a rather deep tan, and the skin of the face is smooth and glistening and devoid of other surface markings. The trunk and extremities show mingling of violaceous and light yellow tints and exhibit innumerable elevated papules and nodules, from the size of a pea to that of a dime, so that almost the entire body appears to be studded with these lesions, which are firmer to touch than the adjacent, nonelevated skin. The papules and nodules vary in color, exhibiting bluish, yellow
Relation of the stage of parasite development in the peripheral blood to prognosis in severe falciparum malaria (1993)

Admission blood films from 72 patients who died of severe falciparum malaria (50 Thai adults, 22 Gambian children) were matched retrospectively for parasitaemia with equal numbers of survivors. The peripheral blood parasites from fatal cases were more mature than those from survivors. Tiny rings (TR) comprised > 50% of parasites in 47/72 (65%) survivors but only 12/72 (17%) of fatal cases (P < 0.001). Parasites containing visible pigment (MTS: mature trophozoites and schizonts) comprised < 20% of the total parasite count in 10/72 (14%) survivors compared with 31/72 (43%) fatal cases (P < 0.001). Of the 39 patients with > 10(4) MTS/microL, 30 (81%) died. These findings were confirmed in a prospective study of 279 adult Thai patients admitted sequentially with acute falciparum malaria. Only 4 of the 19 fatal cases (21%) had > 50% TR, compared with 130 of 260 (50%) survivors, whereas > 20% MTS were found in 10/19 (53%) fatal cases, compared with 28/108 (27%) severe malaria survivors, and 26/155 (17%) patients with moderately severe malaria (P = 0.001). As a predictor of fatal outcome, the finding of either > 10(4) MTS/microL or > 5 x 10(5) parasites/microL in severe malaria had a sensitivity of 90% (95% confidence interval [CI] = 75-97%) and a specificity of 72% (95% CI = 59-86%). These observations are consistent with the hypothesis that a predominance of mature parasites in the peripheral blood reflects a greater sequestered biomass, and thus more severe disease. Simple microscopical assessment of parasite maturity on an admission blood slide provides important pathophysiological and prognostic information in severe falciparum malaria.
Single lymphocyte analysis with a microwell array chip (2007)

Following genomics and proteomics, cytomics, a novel method of looking at life, has emerged for analyzing large populations of cells on a single-cell basis with multiple parameters in a quantitative manner. We have developed a highly integrated live-cell microarray system for analyzing the cellular responses of individual cells using a microwell array chip that has 234,000 microwells each of which is just large enough to fit a single cell. Compared with flow cytometry and microscope-based methods, our system can analyze the history of the cellular responses of a large number of cells. We have successfully applied the system to analyze human antigen-specific B-cells and produced human monoclonal antibodies (MoAb) against hepatitis B virus surface antigen. We have also constructed a mouse system to assess hepatitis B virus-neutralization activity and have demonstrated the neutralization activity of our antibodies. Our technology should expand the horizons of cell analysis as well as enable generation of human MoAb for antibody-based therapeutics and diagnosis for infectious diseases such as hepatitis viruses.
A Nonlinear Mapping for Data Structure Analysis (1969)

An algorithm for the analysis of multivariate data is presented along with some experimental results. The algorithm is based upon a point mapping of N L-dimensional vectors from the L-space to a lower-dimensional space such that the inherent data "structure" is approximately preserved.
An Efficient Fixed Complexity QRD-M Algorithm for MIMO-OFDM using Per-Survivor Slicing (2007)

We propose a reduced complexity QRD-M algorithm based on two techniques: Diagonal Loading Preconditioning (DLP) to mitigate the impact of weak main diagonal elements of the channel matrix, and Per-Survivor Slicing (PSS) to allow for pruning of unnecessary branch computations. Both techniques can be combined. In comparison to previously published detectors, both techniques allow for <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">fixed</i> low complexity that is independent of the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SNR</i> . For PSS, a local slicer carries out <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">P</i> tentative decisions on possible symbols based on the symbol alphabet <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">A</i> of size | <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">A</i> |. Only for the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">P</i> symbols closest in Euclidean distance to the received symbol soft estimate, branch metrics are computed, the remaining | <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">A</i> |- <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">P</i> symbols are dropped. <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</i> survivors are retained at each stage. In addition, we show that the previously proposed MMSE QRD- M algorithm (MQRD-M algorithm) has an error floor at high <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SNR</i> . We show that DLP improves the QRD-M algorithm and outperforms the MQRD-M algorithm. In comparison to MQRD-M algorithm, neither the noise variance needs to be estimated, nor a prefilter (which would require a matrix inversion) is needed. Further, in order to take into account the different strengths of the layers, we propose to partition an available fixed number of branches in relation to the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SNR</i> of the layers. The proposed PSS technique is improved by this approach. DLP and PSS significantly lower the complexity. For 16-QAM modulation in a 4 times 4 MIMO system, e.g., the number of branches using the proposed PSS technique is 31.25% of the ordinary QRD-M algorithm if <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</i> = 16. With DLP used together with PSS, <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</i> can be lowered further, so that with 10.2% of the branches of QRD-M algorithm, only a small loss of 1 dB occurs.
Synthesis and hypertensive activity of neuropeptide Y fragments and analogs with modified N- or C-termini or D-substitutions (1989)

Porcine neuropeptide Y (NPY), NPY fragments, and analogues with D-Xaan, Ala9, D-Ala9, and Met17 substitutions or modifications to the C- or N-termini were synthesized. The synthesis and purification of these peptides was achieved by using routine laboratory strategies and techniques. The ability of these peptides to alter mean arterial pressure (MAP) and heart rate (HR) in conscious rats was monitored for 15 min following intraarterial administration. Potencies and efficacies of these peptides relative to NPY were determined by comparison of dose-response curves. Administration of 40 micrograms/kg NPY resulted in a rapid, though short-lived, rise in mean arterial pressure from a basal value of 107.0 +/- 2.6 to 157 +/- 5.5 mmHg (means +/- sem, n = 13). The ED50 (+/- SE) for this response was 3.04 +/- 0.88 micrograms/kg. Peptide YY (PYY) elicited a response that was similar in magnitude but with an ED50 (+/- SE, n = 3) of 0.76 +/- 0.24 micrograms/kg while porcine pancreatic polypeptide (pPP) was inactive when tested at 40 micrograms/kg (n = 4). Relative potencies for [Ac-Tyr1]NPY, [Ac-D-Tyr1]NPY, [des-amino-Tyr1] NPY, and [Me-Tyr1]NPY ranged from 1.1 to 2.2. Potencies relative to NPY for D-substitutions at positions 2-6 and 8-13 inclusive ranged from 0.1 to 1.0. Analogues with D-substitutions at positions 1-3 exhibited an extended duration of action. Analogues with D-substitutions at positions 33-35 inclusive were inactive at 40 micrograms/kg, and [D-Tyr36]NPY was 10-fold less potent than NPY, suggesting that the integrity of the C-terminal region is critical to the overall biological action of NPY. This conclusion is supported by studies with C- and N-terminal deletion peptides. NPY2-36 showed full intrinsic activity at 40 micrograms/kg and retains 40% of the hypertensive potency of NPY. There was a sequential decrease in efficacy upon further N-terminal deletion. In contrast to the finding with NPY2-36, modification of the C-terminus either from the native carboxamide to the free carboxylic acid or by deletion of the C-terminal residue resulted in analogues which were inactive at 40 micrograms/kg. These data indicate that an essentially full-length, C-terminally amidated NPY structure is required for the hypertensive activity observed in conscious rats upon intraarterial administration of NPY and NPY analogues.