gebhart/patrepeval huggingface dataset:
FTY720 Protects Cardiac Microvessels of Diabetes: A Critical Role of S1P1/3 in Diabetic Heart Disease (2012)

Our study represents that the deregulation of S1P1 and S1P3 is an important signalresponsible for cardiac microvascular dysfunction in diabetes. FTY720 might be competent to serve as a potential therapeutic approach for diabetic heart disease through ameliorating cardiac microvascular barrier impairment and pathologic angiogenesis, which might be partly dependent on PKCβII-mediated signaling pathway.
Supervised Learning in Spiking Neural Networks with ReSuMe: Sequence Learning, Classification, and Spike Shifting (2009)

Learning from instructions or demonstrations is a fundamental property of our brain necessary to acquire new knowledge and develop novel skills or behavioral patterns. This type of learning is thought to be involved in most of our daily routines. Although the concept of instruction-based learning has been studied for several decades, the exact neural mechanisms implementing this process remain unrevealed. One of the central questions in this regard is, How do neurons learn to reproduce template signals (instructions) encoded in precisely timed sequences of spikes? Here we present a model of supervised learning for biologically plausible neurons that addresses this question. In a set of experiments, we demonstrate that our approach enables us to train spiking neurons to reproduce arbitrary template spike patterns in response to given synaptic stimuli even in the presence of various sources of noise. We show that the learning rule can also be used for decision-making tasks. Neurons can be trained to classify categories of input signals based on only a temporal configuration of spikes. The decision is communicated by emitting precisely timed spike trains associated with given input categories. Trained neurons can perform the classification task correctly even if stimuli and corresponding decision times are temporally separated and the relevant information is consequently highly overlapped by the ongoing neural activity. Finally, we demonstrate that neurons can be trained to reproduce sequences of spikes with a controllable time shift with respect to target templates. A reproduced signal can follow or even precede the targets. This surprising result points out that spiking neurons can potentially be applied to forecast the behavior (firing times) of other reference neurons or networks.
Multiplex immunoassay analysis of biomarkers in clinically accessible quantities of human aqueous humor. (2009)

These results demonstrate that multiplex analysis of the aqueous can be a useful tool in screening for any pathophysiological changes of the ocular environment. Moreover, ocular pathology/pathophysiology-specific Multi-analyte profiles MAPs can be developed and used to analyze the aqueous.
Role of the Conserved Acidic Residue Asp21 in the Structure of Phosphatidylinositol 3-Kinase Src Homology 3 Domain:  Circular Dichroism and Nuclear Magnetic Resonance Studies (2000)

To elucidate a role of the Src homology 3 (SH3)-conserved acidic residue Asp21 of the phosphatidylinositol 3-kinase (PI3K) SH3 domain, structural changes induced by the D21N mutation (Asp21 --> Asn) were examined by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopies. In the previous study, we demonstrated that environmental alterations occurred at the side chains of Trp55 and some Tyr residues from the comparison of the near-UV CD spectra of the PI3K SH3 domain with or without a D21N mutation [Okishio, N., et al. (2000) Biopolymers 57, 208-217]. In this work, the affected Tyr residues were identified as Tyr14 and Tyr73 by the CD analysis of a series of mutants, in which every single Tyr residue was replaced by a Phe residue with or without a D21N mutation. The (1)H and (15)N resonance assignments of the PI3K SH3 domain and its D21N mutant revealed that significant chemical shift changes occurred to the aromatic side-chain protons of Trp55 and Tyr14 upon the D21N mutation. All these aromatic residues are implicated in ligand recognition. In addition, the NMR analysis showed that the backbone conformations of Lys15-Asp23, Gly54-Trp55, Asn57-Gly58, and Gly67-Pro70 were affected by the D21N mutation. Furthermore, the (15)N[(1)H] nuclear Overhauser effect values of Tyr14, Glu19, and Glu20 were remarkably changed by the mutation. These results show that the D21N mutation causes structural deformation of more than half of the ligand binding cleft of the domain and provide evidence that Asp21 plays an important role in forming a well-ordered ligand binding cleft in cooperation with the RT loop (Lys15-Glu20).
Glial cell line-derived neurotrophic factor (GDNF) therapy for Parkinson's disease. (2007)

Many studies using animals clarify that glial cell line-derived neurotrophic factor (GDNF) has strong neuroprotective and neurorestorative effects on dopaminergic neurons. Several pilot studies clarified the validity of continuous intraputaminal GDNF infusion to patients with Parkinson's disease (PD), although a randomized controlled trial of GDNF therapy published in 2006 resulted in negative outcomes, and controversy remains about the efficacy and safety of the treatment. For a decade, our laboratory has investigated the efficacy and the most appropriate method of GDNF administration using animals, and consequently we have obtained some solid data that correspond to the results of clinical trials. In this review, we present an outline of our studies and other key studies related to GDNF, the current state of the research, problems to be overcome, and predictions regarding the use of GDNF therapy for PD in the future.
Cycle time and slack optimization for VLSI-chips (1999)

We consider the problem of finding an optimal clock schedule, i.e. optimal arrival times for clock signals at latches of a VLSI chip. We describe a general model which includes all previously considered models. Then we show how to optimize the cycle time and optimally balance slacks on data paths and on clocktree paths. The problem of finding a clock schedule with the optimum cycle time was solved before, either by linear programming or by binary search, using a test for negative circuits in a digraph as a subroutine. We show for the first time that a direct combinatorial algorithm solves this problem optimally. Incidentally, this yields a new efficient method for timing analysis with transparent latches. Moreover, we extend this algorithm to the slack balancing problem: To make the chip less sensitive to routing detours, process variations and manufacturing skew it is desirable to have as few critical paths as possible. We show how to find the clock schedule with minimum number of critical paths (optimum slack distribution) in a well-defined sense. Rather than fixed dock arrival times we show how to obtain as large as possible intervals for the clock arrival times. This can be considered as slack on clocktree paths. Indeed, we can find the global optimum of simultaneous optimization of slacks on all data paths and clocktree paths. All the above is done by very efficient network optimization algorithms, based on parametric shortest paths. Our computational results with recent IBM processor chips show that the number of critical paths decreases dramatically, in addition to a considerable improvement of the cycle time. The running times are reasonable even for the largest designs.
Impact of the cystic fibrosis mutation F508del-CFTR on renal cyst formation and growth (2012)

In autosomal dominant polycystic kidney disease (ADPKD), cystic fibrosis transmembrane conductance regulator (CFTR), the protein product of the gene defective in cystic fibrosis (CF), plays a crucial role in fluid accumulation, which promotes cyst swelling. Several studies have identified individuals afflicted by both ADPKD and CF. Two studies suggested that CF mutations might attenuate the severity of ADPKD, whereas a third found no evidence of a protective effect. In this study, we investigated the impact of the commonest CF mutation F508del-CFTR on the formation and growth of renal cysts. As a model system, we used Madin-Darby canine kidney (MDCK) epithelial cells engineered to express wild-type and F508del human CFTR. We grew MDCK cysts in collagen gels in the presence of the cAMP agonist forskolin and measured transepithelial resistance and Cl(-) secretion with the Ussing chamber technique and assayed cell proliferation using nonpolarized MDCK cells. When compared with untransfected MDCK cells, cells expressing wild-type CFTR generated substantial numbers of large cysts, which grew markedly over time. By contrast, MDCK cells expressing F508del-CFTR formed very few tiny cysts that failed to enlarge. Interestingly, treatment of F508del-CFTR cysts with the CFTR corrector VRT-325 and the CFTR corrector-potentiator VRT-532 increased the number, but not size, of F508del-CFTR cysts, possibly because VRT-325 inhibited strongly cell proliferation. Based on its effects on transepithelial resistance, Cl(-) secretion, and cell proliferation, we conclude that the F508del-CFTR mutation disrupts cyst formation and growth by perturbing strongly fluid accumulation within the cyst lumen without compromising epithelial integrity.
Cold-War Stealth Science Can Aid Seismic Interpretation (1998)

This article is taken from an original manuscript, "Submarine Stealth Technology Now Aids Subsalt Navigation."
An Empirical Study of Optimizing Cognitive Load in Multimedia Integrated English Teaching (2014)

Cognitive load is one of the important factors influencing complex learning. The article introduces relevant research in optimizing cognitive load in multimedia learning at abroad and in China. Results of the empirical study of the instructional design in the multimedia Integrated English show that the means of all the scores in the tests and the number of the students who pass the TEM-4 in the experimental group are higher than those in the control group, among which significant differences can be found in Cloze, Vocabulary and Structure Reading Comprehension, Paraphrasing and Total Score between the experimental group and the controlled group whereas no significant differences exist in their average score in Translation and Writing. The study indicates that optimizing cognitive load in the multimedia learning facilitates improving English learning efficiency.
Infrared microspectroscopic imaging of the cerebellum of normal and cytarabine treated rats. (1998)

Conventionally, the diagnosis of neuropathology in a subject requires the identification of a behavioral modification, which provides direction for appropriate histological analyses. However, since the ultimate diagnosis of the pathology largely depends on the initial choice of histological tests, the opportunity exists for inaccurate or insensitive results. An innovative approach using Fourier transform infrared (FT-IR) spectroscopic imaging to diagnose neuropathology should prove useful. This novel method monitors and visualizes the underlying chemistry of the tissue, based on hundreds of vibrational absorption bands that are intrinsic to the sample. As such, it makes no prior assumptions as to the type or degree of pathology. Using this technique, we have spectroscopically imaged cerebellar tissue slices from rats [control subjects and subjects treated with the antineoplastic drug, cytarabine (Ara-C)], and have been able to correlate lipid and protein distributions within distinct cell types in the cerebellum. A further benefit of the technique is that it simultaneously records tens of thousands of independent spectra from different spatial locations within the sample. Thus, a variety of statistical and multivariate techniques can be exploited to characterize large sample areas and to provide robust classification of individual spectral signatures. In comparison to standard histological protocols, FT-IR spectroscopic imaging simultaneously analyzes cell layers and identifies subtle structural and biochemical changes within the sample. We suggest that FT-IR spectroscopic imaging should provide a highly reliable, complementary tool for standard histological tier testing.
Ionizing radiation regulates expression of the c-jun protooncogene. (1990)

There is little known about the regulation of gene expression by ionizing radiation exposure. The present studies demonstrate transcriptional activation of a mammalian gene, the c-jun protooncogene, by x-rays. The c-jun gene encodes a component of the AP-1 protein complex and is important in early signaling events involved in various cellular functions. The increase in c-jun transcripts by ionizing radiation was time- and dose-dependent as determined by Northern blot analysis. Transcriptional run-on analysis demonstrated that ionizing radiation stimulates the rate of c-jun gene transcription. Furthermore, the half-life of c-jun RNA was prolonged in the absence of protein synthesis. These findings indicate that the increase in c-jun RNA observed after irradiation is regulated by transcriptional and posttranscriptional mechanisms. Moreover, the induction of c-jun by ionizing radiation was associated with an inverse dose rate effect in that decreasing the dose rate resulted in increased c-jun expression. The present results similarly demonstrate that ionizing radiation increases levels of c-fos transcripts as well as that of jun-B, another member of the jun family. Taken together, these results suggest a role for induction of early response genes in the pathophysiologic effects of ionizing radiation.
Craniofacial Tissue Engineering (2001)

There is substantial need for the replacement of tissues in the craniofacial complex due to congenital defects, disease, and injury. The field of tissue engineering, through the application of engineering and biological principles, has the potential to create functional replacements for damaged or pathologic tissues. Three main approaches to tissue engineering have been pursued: conduction, induction by bioactive factors, and cell transplantation. These approaches will be reviewed as they have been applied to key tissues in the craniofacial region. While many obstacles must still be overcome prior to the successful clinical restoration of tissues such as skeletal muscle and the salivary glands, significant progress has been achieved in the development of several tissue equivalents, including skin, bone, and cartilage. The combined technologies of gene therapy and drug delivery with cell transplantation will continue to increase treatment options for craniofacial cosmetic and functional restoration.
Efficacy and Safety of Rasburicase (recombinant urate oxidase) for the Prevention and Treatment of Hyperuricemia During Induction Chemotherapy of Aggressive Non-Hodgkin’s Lymphoma: Results of the GRAAL1 (Groupe d’Etude des Lymphomes de l’Adulte Trial on Rasburicase Activity in Adult Lymphoma) Study (2003)

Rasburicase is the treatment of choice to control UA and prevent tumor lysis syndrome in adult patients with aggressive NHL.
Photoimmunodiagnosis with antibody-fluorescein conjugates: In vitro and in vivo preclinical studies (1992)

The use of dyes has been helpful for the photodiagnosis of small cancers accessible to endoscopic examn. An important limiting factor of this technol. is that the presently used fluorescent dye mixt. has a relatively poor capacity to accumulate preferentially in malignant tissue and a low quantum yield of fluorescence. To improve these parameters, fluorescein was coupled to an anti-carcinoembryonic antigen (CEA) MAb and the biodistribution of several conjugates was studied in nude mice bearing a human colon carcinoma xenograft. In vitro, such conjugates with fluorescein to MAb molar ratios ranging 4-19, trace labeled with 125I, showed &gt;82% binding to insolubilized CEA. However, since the aim of this work was the evaluation of MAb-dye conjugates designed for in vivo tumor localization, all newly prepd. MAb-fluorescein conjugates were tested in the exptl. model of nude mice bearing CEA expressing human colon carcinoma xenografts. Under these exptl. in vivo conditions, the conjugate contg. 10 fluorescein mols. per MAb mol. gave an excellent tumor localization (up to 30% of the injected dose per g tumor at 24 h), whereas a conjugate with 19 fluorescein mols. per MAb mol. gave almost no in vivo localization in the tumor, probably due to a very short half-life. Tumor-to-liver, -kidney, and -muscle ratios of 20, 30, and 72, resp., were obtained at 48 h after injection of the conjugate contg. 10 fluorescein mols. per MAb mol. In the spectrofluorometric anal., a high fluorescence intensity was obsd. in the tumor after injection of the anti-CEA MAb conjugate. To compare these results with a conventionally used dye, mice bearing the same xenografts received a purified form of hematoporphyrin, Photofrin II. The intensity of the fluorescence signal of the tumor after an injection of 0.44 mg fluorescein coupled to 20 mg of MAb was 8-fold higher than that obtained after injection of 60 mg of Photofrin II. These results illustrate the possibility of improving the specificity of in vivo tumor localization of dyes for laser-induced fluorescence photodetection and phototherapy by coupling them to MAb directed against tumor markers.
Electrospray Deposition as a Method for Mass Fabrication of Mono- and Multicomponent Microarrays of Biological and Biologically Active Substances (1999)

Electrospray of protein and DNA solutions is currently used to generate ions for mass spectrometric analysis of these molecules. Deposition of charged electrospray products on certain areas of a substrate under control of electrostatic forces is suggested here as a method for fabrication of multiple deposits of any size and form. For example, multiple dots of protein, DNA, or other organic substances can be deposited simultaneously through an array of holes in a dielectric mask covering any slightly conductive substrate (membrane, wet glass, semiconductor, etc.). If every new substance is deposited after a shift of the mask with respect to the substrate, a multicomponent matrix is created under each hole. It is demonstrated that dots as small as 2-6 microns can be fabricated by such an electrospray deposition (ESD). It is also demonstrated that the ES-deposited proteins and DNA retain their ability to specifically bind antibodies and matching DNA probes, respectively, enabling use of the ESD fabricated matrixes in Dot Immuno-Binding (DIB) and in DNA hybridization assays.
Projection displays using red, green, and blue solid-state laser light sources (2003)

Experiments have been carried out on light valve projectors to compare the efficiency of a projector using solid state lasers in all three primary colours.
Up-regulated Smad5 Mediates Apoptosis of Gastric Epithelial Cells Induced by Helicobacter pylori Infection (2003)

The gastric pathogen Helicobacter pylori activates epithelial cell signaling pathways, and its infection induces changes in the expression of several genes in infected human gastric tissues. Recent studies have indicated that the ability of H. pylori to regulate epithelial cell responses depends on the presence of an intact cag pathogenicity island (cagPAI). We investigated altered mRNA expression of gastric epithelial cells after infection with H. pylori, both cagPAI-positive and cagPAI-negative strains, by cDNA microarray, reverse transcription PCR, and Northern blot analysis. Our results indicated that cagPAI-positive H. pylori strains (ATCC 43504 and clinical isolated strains) significantly activated Smad5 mRNA expression of human gastric epithelial cells (AGS, KATOIII, MKN28, and MKN45). We further examined whether the up-regulated Smad5 was related to apoptosis of gastric epithelial cells induced by H. pylori. Smad5 RNA interference completely inhibited H. pylori-induced apoptosis. These results suggest that Smad5 is up-regulated in gastric epithelial cells through the presence of cagPAI of H. pylori and that Smad5 mediates apoptosis of gastric epithelial cells induced by H. pylori infection.
Expression of potassium channels during postnatal differentiation of rabbit Müller glial cells (1999)

The postnatal maturation of Müller glial cells from immature radial glial cells is accompanied by specific changes in the activity of distinct types of K+ channels, as shown by whole-cell and cell-attached records on freshly isolated cells from retinae of young (postnatal days 1-30, P1-P30) and adult rabbits. (i) The density of inwardly rectifying currents, providing the main K+ conductance in adult Müller cells, was very low (0.8 pA/pF) from P1 to P6 but increased rapidly thereafter until a relatively stable level of 11.0 pA/pF was established at P17. (ii) Transient (A-type) K+ currents were expressed in all immature cells at a high density (9.6 pA/pF). After P12, both the percentage of cells with A-type currents and the peak amplitudes of the currents (2.8 pA/pF) declined. (iii) Delayed rectifying K+ currents developed slowly until after P30. (iv) The postnatal maturation of radial glial cells was accompanied by a strong decrease in the activity of large-conductance, Ca2+-activated K+ channels, the open probability of which (measured at the resting membrane potential) decreased from 0.69 at P2-4 to 0.06 at P13-14. The developmental decrease of the activity of Ca2+-activated K+ channels is assumed to be mainly caused by alteration of the resting membrane potential which developed from low values (-49 mV) at P1-6 to high adult values (-84 mV) after P13. The activity of each distinct type of K+ channel investigated is differently modulated by developmental regulation. This may reflect different functional requirements of immature and mature Müller cells.
Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease (2007)

Inflammatory bowel disease (IBD), the most important being Crohn's disease and ulcerative colitis, results from chronic dysregulation of the mucosal immune system in the gastrointestinal tract. Although the pathogenesis of IBD remains unclear, it is widely accepted that genetic, environmental, and immunological factors are involved. Recent studies suggest that intestinal epithelial defenses are important to prevent inflammation by protecting against microbial pathogens and oxidative stresses. To investigate the etiology of IBD, animal models of experimental colitis have been developed and are frequently used to evaluate new anti-inflammatory treatments for IBD. Several models of experimental colitis that demonstrate various pathophysiological aspects of the human disease have been described. In this manuscript, we review the characteristic features of IBD through a discussion of the various chemically induced experimental models of colitis (e.g. dextran sodium sulfate-, 2,4,6-trinitrobenzene sulfonic acid-, oxazolone-, acetic acid-, and indomethacin-induced models). We also summarize some regulatory and pathogenic factors demonstrated by these models that can, hopefully, be exploited to develop future therapeutic strategies against IBD.
Effects of the histone deacetylase inhibitor valproic acid on Notch signalling in human neuroblastoma cells (2005)

Neuroblastoma (NB), a sympathetically derived childhood tumour, shows characteristics of neuronal precursor cells, suggesting a halted differentiation process. We have previously shown that the Notch signalling cascade, a key player during normal neurogenesis, also might be involved in NB differentiation. Valproic acid (VPA), a well-tolerated antiepileptic drug, has been shown to induce differentiation and cell death of NB cells, possibly associated with its recently described HDAC inhibiting activity. Stimulation of NB cells with VPA led to increased cell death and phenotypic changes associated with differentiation, that is, neurite extension and upregulation of neuronal markers. VPA treatment also led to an activated Notch signalling cascade as shown by increased levels of intracellular Notch-1 and Hes-1, mimicking the initial phase of induced differentiation. These results reinforce that VPA potentially could be used in differentiation therapy of NB and that the effects in part could be a consequence of interference with the Notch signalling cascade.