gebhart/patrepeval huggingface dataset:
Growing radial basis neural networks: merging supervised and unsupervised learning with network growth techniques (1997)

This paper proposes a framework for constructing and training radial basis function (RBF) neural networks. The proposed growing radial basis function (GRBF) network begins with a small number of prototypes, which determine the locations of radial basis functions. In the process of training, the GRBF network gross by splitting one of the prototypes at each growing cycle. Two splitting criteria are proposed to determine which prototype to split in each growing cycle. The proposed hybrid learning scheme provides a framework for incorporating existing algorithms in the training of GRBF networks. These include unsupervised algorithms for clustering and learning vector quantization, as well as learning algorithms for training single-layer linear neural networks. A supervised learning scheme based on the minimization of the localized class-conditional variance is also proposed and tested. GRBF neural networks are evaluated and tested on a variety of data sets with very satisfactory results.
AD Vaccines: Conclusions and Future Directions (2009)

disease and Huntington's chorea. Immunomodulation holds great promise as a disease altering therapeutic approach for all these disorders. For example, it has been shown that prion directed mucosal vaccination can prevent infection from an exogenous source Ultimately, the successful application of immunomodulation approaches may lead to dramatic novel interventions for a wide spectrum of age associated diseases.
Production of lovastatin from rice straw using Aspergillus terreus in solid state fermentation (2013)

Responce surface methodology (RSM) was used to optimize&nbsp; production of lovastatin from rice straw in solid state fermentation by&nbsp;Aspergillus terreus&nbsp;ATCC 74135.&nbsp;A four-factor-five-level central composite design (CCD) was used&nbsp; to examine the combining effects of temprature, moisture, inoculum and pH on lovastatin production.&nbsp; Results of the CCD study showed&nbsp; that only temperature and moisture contents significantly affected (P&lt;0.01) lovastatin production. The maximum lovastatin production from experimentation and predicted by the CCD were 351.54 and 357.54 mg/kgDM, respectively, under the optimal conditions of&nbsp; 51.19% moisture, 28.29&deg;C incubation temperature, inoculum size of 10.26% and pH of 6.31. Results of the present study showed that lovastatin can be produced from rice straw in solid state fermentation and the lovastatin enriched rice straw has the potential to be used as feed ingredient for reduction of ruminal methanogenesis. &nbsp; Key words:&nbsp;Lovastatin, solid state fermentation,&nbsp;Aspergillus terreus, rice straw, responce surface methodology.
Improved Protocols for Illumina Sequencing (2014)

In this unit, we describe a set of improvements that have been made to the standard Illumina protocols to make the sequencing process more reliable in a high-throughput environment, reduce amplification bias, narrow the distribution of insert sizes, and reliably obtain high yields of data.
Genome-Wide Identification of Regulatory DNA Elements and Protein-Binding Footprints Using Signatures of Open Chromatin in Arabidopsis (2012)

Gene expression and regulation in eukaryotes is controlled by orchestrated binding of regulatory proteins, including both activators and repressors, to promoters and other cis-regulatory DNA elements. An increasing number of plant genomes have been sequenced; however, a similar effort to the ENCODE project, which aimed to identify all functional elements in the human genome, has yet to be initiated in plants. Here we report genome-wide high-resolution mapping of DNase I hypersensitive (DH) sites in the model plant Arabidopsis thaliana. We identified 38,290 and 41,193 DH sites in leaf and flower tissues, respectively. The DH sites were depleted of bulk nucleosomes and were tightly associated with RNA polymerase II binding sites. Approximately 90% of the binding sites of two well-characterized MADS domain transcription factors, APETALA1 and SEPALLATA3, were covered by the DH sites. We demonstrate that protein binding footprints within a specific genomic region can be revealed using the DH site data sets in combination with known or putative protein binding motifs and gene expression data sets. Thus, genome-wide DH site mapping will be an important tool for systematic identification of all cis-regulatory DNA elements in plants.
The family of the IL-6-Type cytokines: Specificity and promiscuity of the receptor complexes (1997)

The cytokines IL-6, LIF, CNTF, OSM, IL-11, and CT-1 have been grouped into the family of IL-6-type cytokines, since they all require gp130 for signal transduction. Interestingly, gp130 binds directly to OSM, whereas complex formation with the other cytokines depends on additional receptor subunits. Only limited structural information on these cytokines and their receptors is available. X-ray structures have been solved for the cytokines LIF and CNTF, whose up-up-down-down four-helix bundle is common to all of these cytokines, and for the receptors of hGH and prolactin, which contain two domains with a fibronectin III-like fold. Since cocrystallization and x-ray analysis of the up to four different proteins forming the receptor complexes of the IL-6-type cytokines is unlikely to be achieved in the near future, model building based on the existing structural information is the only approach for the time being. Here we present model structures of the complexes of human and murine IL-6 with their receptors. Their validity can be deduced from the fact that published mutagenesis data and the different receptor specificity of human and murine IL-6 can be understood. It is now possible to predict the relative positions and contacts for all molecules in their respective complexes. Such information can be used for the rational design of cytokine and receptor antagonists, which may have a valuable therapeutic perspective.
Gold Nanoparticle−Cytochrome c Complexes:  The Effect of Nanoparticle Ligand Charge on Protein Structure (2005)

We report the effect of nanoparticle ligand charge on the structure of a covalently, site-specifically linked protein. Au nanoparticles with positive, negative, and neutral ligands were appended to a specific cysteine, C102, of Saccharomyces cerevisiae cytochrome c. Conjugates were purified by HPLC or gel electrophoresis. Circular dichroism spectroscopy shows that changing the nanoparticle ligand dramatically influences the attached cytochrome c structure. The protein retains its structure with neutral ligands but denatures in the presence of charged species. This is rationalized by the electrostatic interaction of amino acids in the local vicinity of C102 with the endgroups of the ligand.
Treatment of Mild Cognitive Impairment (MCI) (2009)

Mild cognitive impairment (MCI), an intermediate stage between normalcy and dementia, is characterized by fewer symptoms and less functional decline than dementia with less established biological disease processes and is an attractive target for both symptomatic and disease progression therapies. It is always desirable to treat symptoms or slow disease at a stage where the individual is still largely functional. Therapeutic studies in MCI have either been symptomatic, usually of shorter duration or of longer multiyear terms to demonstrate whether disease progression is delayed. Symptomatic agents tested to date include donepezil, SGS-742, and Piracetam. No symptomatic drug study has demonstrated clinically convincing differences between placebo and the study medication. Disease progression trials in MCI investigations of 2 to 4 year durations have included donepezil, vitamin E, rivastigmine, galantamine and rofecoxib. None have demonstrated convincing effects in delaying longer term disease progression or conversion to dementia. Problems that may have undermined these trials; i) disease heterogeneity, ii) slow early progression of the disease, and iii) insensitive cognitive and functional instruments. Future MCI studies may benefit from the use of biomarkers such as apolipoprotein E (APOE4), cerebrospinal fluid amyloid-beta1-42 and Tau levels and PIB positivity on brain PET scans as well as more sensitive neuropsychological test measures may also more accurately reflect clinical changes related to drug effects.
The Human Gut Chip “HuGChip”, an Explorative Phylogenetic Microarray for Determining Gut Microbiome Diversity at Family Level (2013)

Evaluating the composition of the human gut microbiota greatly facilitates studies on its role in human pathophysiology, and is heavily reliant on culture-independent molecular methods. A microarray designated the Human Gut Chip (HuGChip) was developed to analyze and compare human gut microbiota samples. The PhylArray software was used to design specific and sensitive probes. The DNA chip was composed of 4,441 probes (2,442 specific and 1,919 explorative probes) targeting 66 bacterial families. A mock community composed of 16S rRNA gene sequences from intestinal species was used to define the threshold criteria to be used to analyze complex samples. This was then experimentally verified with three human faecal samples and results were compared (i) with pyrosequencing of the V4 hypervariable region of the 16S rRNA gene, (ii) metagenomic data, and (iii) qPCR analysis of three phyla. When compared at both the phylum and the family level, high Pearson's correlation coefficients were obtained between data from all methods. The HuGChip development and validation showed that it is not only able to assess the known human gut microbiota but could also detect unknown species with the explorative probes to reveal the large number of bacterial sequences not yet described in the human gut microbiota, overcoming the main inconvenience encountered when developing microarrays.
Uncoupling Protein-3 Is a Mediator of Thermogenesis Regulated by Thyroid Hormone, β3-Adrenergic Agonists, and Leptin (1997)

Mitochondrial uncoupling proteins (UCPs) are transporters that are important for thermogenesis. The net result of their activity is the exothermic movement of protons through the inner mitochondrial membrane, uncoupled from ATP synthesis. We have cloned a third member of the UCP family, UCP3. UCP3 is expressed at high levels in muscle and rodent brown adipose tissue. Overexpression in yeast reduced the mitochondrial membrane potential, showing that UCP3 is a functional uncoupling protein. UCP3 RNA levels are regulated by hormonal and dietary manipulations. In contrast, levels of UCP2, a widely expressed UCP family member, showed little hormonal regulation. In particular, muscle UCP3 levels were decreased 3-fold in hypothyroid rats and increased 6-fold in hyperthyroid rats. Thus UCP3 is a strong candidate to explain the effects of thyroid hormone on thermogenesis. White adipose UCP3 levels were greatly increased by treatment with the beta3-adrenergic agonist, CL214613, suggesting another pathway for increasing thermogenesis. UCP3 mRNA levels were also regulated by dexamethasone, leptin, and starvation, albeit differently in muscle and brown adipose tissue. Starvation caused increased muscle and decreased BAT UCP3, suggesting that muscle assumes a larger role in thermoregulation during starvation. The UCP3 gene is located close to that encoding UCP2, in a chromosomal region implicated in previous linkage studies as contributing to obesity.
Agonistic Human Antibodies Binding to Lecithin-Cholesterol Acyltransferase Modulate High Density Lipoprotein Metabolism (2015)

Drug discovery opportunities where loss-of-function alleles of a target gene link to a disease-relevant phenotype often require an agonism approach to up-regulate or re-establish the activity of the target gene. Antibody therapy is increasingly recognized as a favored drug modality due to multiple desirable pharmacological properties. However, agonistic antibodies that enhance the activities of the target enzymes are rarely developed because the discovery of agonistic antibodies remains elusive. Here we report an innovative scheme of discovery and characterization of human antibodies capable of binding to and agonizing a circulating enzyme lecithin cholesterol acyltransferase (LCAT). Utilizing a modified human LCAT protein with enhanced enzymatic activity as an immunogen, we generated fully human monoclonal antibodies using the XenoMouse(TM) platform. One of the resultant agonistic antibodies, 27C3, binds to and substantially enhances the activity of LCAT from humans and cynomolgus macaques. X-ray crystallographic analysis of the 2.45 Å LCAT-27C3 complex shows that 27C3 binding does not induce notable structural changes in LCAT. A single administration of 27C3 to cynomolgus monkeys led to a rapid increase of plasma LCAT enzymatic activity and a 35% increase of the high density lipoprotein cholesterol that was observed up to 32 days after 27C3 administration. Thus, this novel scheme of immunization in conjunction with high throughput screening may represent an effective strategy for discovering agonistic antibodies against other enzyme targets. 27C3 and other agonistic human anti-human LCAT monoclonal antibodies described herein hold potential for therapeutic development for the treatment of dyslipidemia and cardiovascular disease.
Multiscale-based image enhancement (2002)

Wavelet-based image analysis offers the opportunity to enhance images using features extracted at different scales and subbands. We propose a two-part wavelet domain image enhancement method. First, we apply a locally adaptive filter to the wavelet transform detail coefficients to simultaneously suppress noise and enhance edge contrast. Our estimates of noise variance behaviour across the decomposition scales and subbands are based on simulations. To enhance contrast between large, flat image regions, we apply global histogram equalisation to the wavelet transform approximation coefficients at the coarsest decomposition level.
Dietary Olive Oil Reduces Low-Density Lipoprotein Uptake by Macrophages and Decreases the Susceptibility of the Lipoprotein to Undergo Lipid Peroxidation (1993)

Low-density lipoprotein (LDL) oxidation and macrophage cholesterol accumulation are both involved in atherogenesis. Recently it was shown that feeding rabbits or humans with an oleic-acid-rich diet reduced the susceptibility of their LDL to in vitro oxidation. Since olive oil is highly enriched with oleic acid, we tested the effect of olive oil supplementation (50 g/day) to the diet of 10 healthy male subjects, during a 2-week period, on macrophage uptake of their LDL and on the propensity of their LDL to oxidation (with copper ions). Olive oil supplementation to the diet resulted in LDL enrichment with oleic acid (C18:1) and sitosterol. No effect on plasma cholesterol levels was found, but the LDL cholesteryl ester content was reduced (16%) whereas its unesterified cholesterol was increased (41%). Even after 1 week of the olive oil diet, the LDL susceptibility to in vitro oxidation was significantly reduced (p < 0.01). Macrophage uptake of LDL was studied by analysis of cellular cholesterol content and by analysis of the macrophage cholesterol esterification rates. LDL obtained after 1 and 2 weeks of the olive oil diet demonstrated reduced cellular uptake in comparison with LDL obtained before the supplementation of olive oil, by 50 and 61%, respectively. The LDL resistance to oxidation was shown by a reduction in its peroxide, malondialdehyde and conjugated diene content by 73, 28 and 32%, respectively. LDL incubation with oleic acid for the period of its oxidation with copper ions demonstrated a dose-dependent inhibition of lipoprotein oxidation by up to 72% as opposed to linoleic and arachidonic acids (50 microM) which increased LDL oxidation by 22 and 72%, respectively. Sitosterol, in a similar incubation system, inhibited LDL oxidation by up to 26%. We conclude that olive oil supplementation to the diet modifies LDL lipid composition and enriches the lipoprotein with oleic acid and sitosterol. The antiatherogenic properties of this modified lipoprotein may be related to its resistance to in vitro peroxidation and its reduced uptake by macrophages.
Organization-Induced Charge Redistribution in Self-Assembled Organic Monolayers on Gold (2005)

The charge redistribution that occurs within dipolar molecules as they self-assemble into organized organic monolayer films has been studied. The extent of charge transfer is probed by work function measurements, using low-energy photoelectron spectroscopy (LEPS), contact potential difference (CPD), and X-ray photoelectron spectroscopy (XPS), with the latter providing fine details about the internal charge distribution along the molecule. In addition, two-photon photoelectron spectroscopy is applied to investigate the electronic structure of the adsorbed layers. We show that charge transfer acts to reduce the dipole-dipole interaction between the molecules but may either decrease or increase the molecule-to-surface dipole moment.
Mutation of BCL-6 Gene in Normal B Cells by the Process of Somatic Hypermutation of Ig Genes (1998)

Immunoglobulin (Ig) genes are hypermutated in B lymphocytes that are the precursors to memory B cells. The mutations are linked to transcription initiation, but non-Ig promoters are permissible for the mutation process; thus, other genes expressed in mutating B cells may also be subject to somatic hypermutation. Significant mutations were not observed in c-MYC, S14, or alpha-fetoprotein (AFP) genes, but BCL-6 was highly mutated in a large proportion of memory B cells of normal individuals. The mutation pattern was similar to that of Ig genes.
Activation of somatostatin receptor subtype 2 inhibits acid secretion in rats (1995)

Somatostatin is a potent inhibitor of gastric acid secretion. Recently, at least five distinct somatostatin receptor subtypes (SSTR) have been characterized and evaluated using relatively selective peptide analogues of somatostatin. We sought to determine which somatostatin receptor subtypes are involved in peripheral regulation of gastric acid secretion. Fasted, male Sprague-Dawley rats were anesthetized and were implanted with a double-lumen cannula in the stomach. Acid secretion was measured in gastric samples collected every 10 min by backtitration to pH 7. After a 30-min basal period, a 2-h intravenous infusion of pentagastrin (24 micrograms.kg-1.h-1 i.v.) was started. During the second pentagastrin hour, a 1-h intravenous infusion of either vehicle (0.1% canine serum albumin in 0.9% saline) or somatostatin receptor agonists was begun. The somatostatin receptor agonists included peptides with relative specificity for SSTR1-5 (somatostatin-14; 10 nmol.kg-1.h-1); SSTR2, SSTR3, and SSTR5 [SMS-(201-995); 10 nmol.kg-1.h-1]; SSTR2 (1-1,000 nmol.kg-1.h-1); SSTR3 (10-1,000 nmol.kg-1.h-1); and SSTR5 (10-1,000 nmol.kg-1.h-1). The SSTR2 agonist decreased pentagastrin-stimulated acid secretion dose dependently, from 82 +/- 7% of maximum acid output at 1 nmol.kg-1.h-1 to 4 +/- 7% of maximum at 100 nmol.kg-1.h-1. At 10 nmol.kg-1.h-1, the SSTR2 agonist inhibited acid secretion (40 +/- 7% of maximum) similarly to somatostatin (37 +/- 4% of maximum) and SMS-(201-995) (31 +/- 4% of maximum). The SSTR2 agonist inhibited acid secretion approximately 10- to 100-fold more potently than either the SSTR3 or the SSTR5 agonist. These results indicate that somatostatin regulates gastric acid secretion by activation of SSTR2 receptors.
GENE TRANSFER OF IMMUNOMODULATORY PEPTIDES CORRELATES WITH HEME OXYGENASE-1 INDUCTION AND ENHANCED ALLOGRAFT SURVIVAL 1 (2000)

These results demonstrate that plasmid mediated gene transfer is an effective means for delivering immunosuppressive peptides to extend allograft survival. The experiments suggest that these peptides may act by increasing HO-1 activity and support a role for HO-1 in immune regulation and allograft survival.
A recessive defect in lymphocyte or granulocyte function caused by an integrated transgene. (1992)

A line of transgenic mice has been identified with a recessive defect in lymphocyte or granulocyte function, presumably as a result of insertional mutagenesis by the integrated transgene. Transgenic mice homozygous for the transgene integrant showed nearly complete absence of lymphocytes in peripheral lymph nodes and Peyer's patches, a severely diminished thymus medulla, and a greatly enlarged spleen. These animals also developed a syndrome characterized by granulocyte and mononuclear infiltrates in numerous tissues, including skin, liver, and lung, and immunoglobulin deposits in kidney glomeruli. Lung infiltrates were specifically localized around large blood vessels and bronchi, accompanied in some cases by destruction of arterial walls. The light scatter profile of spleen lymphocytes suggested an extremely high percentage of blast cells. Because tissue development and morphology appears to be normal in all other tissues observed, the genetic lesion appears to specifically affect the regulation of lymphocyte or granulocyte activation.
Molecular Mechanisms Involved in the Growth Stimulation of Breast Cancer Cells by Leptin (2004)

Obesity is a risk factor for breast cancer in postmenopausal women. Leptin, an adipocyte-derived cytokine, elicits proliferative effects in some cell types and potentially stimulates the growth of mammary epithelium. Here we show that leptin induced time- and dose-dependent signal transducer and activator of transcription 3 (STAT3) phosphorylation and extracellular signal-regulated kinase (ERK) 1/2 kinase activation in breast carcinoma cells. Blocking STAT3 phosphorylation with a specific inhibitor, AG490, abolished leptin-induced proliferation of MCF-7 cells, whereas blocking ERK1/2 activation by a specific ERK1/2 kinase inhibitor, U0126, did not result in any significant changes in leptin-induced cell proliferation. Our experiments also showed that one member of the p160 family of steroid receptor coactivators, steroid receptor coactivator (SRC)-1, but not glucocorticoid receptor interacting protein 1 (GRIP1) or amplified in breast cancer 1 (AIB1), also functioned in gene transactivation in response to leptin treatment. Glutathione S-transferase pull-down experiments showed that SRC-1 physically interacted with the activation domain of STAT3 and that chromatin immunoprecipitation experiments detected the occupancy of SRC-1, but not GRIP1 or AIB1, on the promoter of STAT3 target genes. Our experiments collectively showed that SRC-1 is involved in STAT3 signaling pathway that is implicated in leptin-stimulated cell growth.