gebhart/patrepeval huggingface dataset:
Bioavailability Challenges Associated with Development of Anti-Cancer Phenolics (2010)

Phenolics including many polyphenols and flavonoids have the potentials to become chemoprevention and chemotherapy agents. However, poor bioavailability limits their biological effects in vivo. This paper reviews the factors that affect phenolics absorption and their bioavailabilities from the points of view of their physicochemical properties and disposition in the gastrointestinal tract. The up-to-date research data suggested that solubility and metabolism are the primary reasons that limit phenolic aglycones' bioavailability although stability and poor permeation may also contribute to the poor bioavailabilities of the glycosides. Future investigations should further optimize phenolics' bioavailabilities and realize their chemopreventive and chemotherapeutic effects in vivo.
Vascular reactivity, tissue levels, and binding sites for endothelin: a comparison in the spontaneously hypertensive and Wistar–Kyoto rats (1991)

The role of endothelin (ET-1) in mediating the development of blood pressure was investigated in the spontaneously hypertensive (SHR) rat using the Wistar-Kyoto (WKY) rat as the normotensive control. The following were characterized in both rat strains: age-dependent changes in mean arterial blood pressure (MAP), tissue (blood, lung, heart, and kidney) levels of immunoreactive ET-1 like related peptides (ET-1RP), aortic ring responses to ET-1, and specific high-affinity tissue (lung, atrium, ventricle, aorta, and kidney) binding sites for 125I-labelled ET-1. Commencing at age 10 weeks through to 12 weeks, SHR rats but not WKY rats developed a significant increase in MAP (from 152 +/- 7 to 189 +/- 3 mmHg) (1 mmHg = 133.32 Pa). However, in both WKY and SHR rats immunoreactive levels of ET-1RP increased (100 and 80%, respectively) throughout the same measurement period. The potency of ET-1 to contract aortic rings from SHR rats was slightly but not significantly greater than that for aortic rings from WKY rats, although aortic rings from SHR rats contracted in the presence of 0.5 nM ET-1, while those from WKY rats did not. The levels of immunoreactive ET-1RP were significantly reduced (32%) in the kidney and unchanged in the heart and lung of SHR rats compared with WKY rats. Specific 125I-labelled ET-1 binding sites displayed an increase and a significant decrease (24%) of density in the atrium and ventricle, respectively, a significant increase (31%) of affinity in the lung, and were unchanged in the kidney and aorta of SHR rats compared with WKY rats following the development of hypertension. The lack of a correlation between circulating levels of immunoreactive ET-1RP and the development of hypertension coupled with a lack of significant differences in vascular reactivity suggest that ET-1 is not the sole mediator of hypertension in this animal model. However, the tissue-specific changes in immunoreactive ET-1RP and 125I-labelled ET-1 binding sites suggest that ET-1 may be a partial mediator of hypertension and is subject to compensatory changes in response to the increased total peripheral resistance in SHR rats.
Grouped graphical Granger modeling for gene expression regulatory networks discovery (2009)

We consider the problem of discovering gene regulatory networks from time-series microarray data. Recently, graphical Granger modeling has gained considerable attention as a promising direction for addressing this problem. These methods apply graphical modeling methods on time-series data and invoke the notion of 'Granger causality' to make assertions on causality through inference on time-lagged effects. Existing algorithms, however, have neglected an important aspect of the problem--the group structure among the lagged temporal variables naturally imposed by the time series they belong to. Specifically, existing methods in computational biology share this shortcoming, as well as additional computational limitations, prohibiting their effective applications to the large datasets including a large number of genes and many data points. In the present article, we propose a novel methodology which we term 'grouped graphical Granger modeling method', which overcomes the limitations mentioned above by applying a regression method suited for high-dimensional and large data, and by leveraging the group structure among the lagged temporal variables according to the time series they belong to. We demonstrate the effectiveness of the proposed methodology on both simulated and actual gene expression data, specifically the human cancer cell (HeLa S3) cycle data. The simulation results show that the proposed methodology generally exhibits higher accuracy in recovering the underlying causal structure. Those on the gene expression data demonstrate that it leads to improved accuracy with respect to prediction of known links, and also uncovers additional causal relationships uncaptured by earlier works.
Investigation of the Short-Term Effect of Chemonucleolysis with Chondroitinase ABC. (2001)

Chondroitinase ABC (C-ABC) is expected to be a novel agent for chemonucleolysis. The effect of C-ABC was investigated by magnetic resonance (MR) and radiograph. C-ABC was administered into the lumbar intervertebral disks on the clinically normal beagles (n=5), in a dose of 50 microl (12.5 units as C-ABC). MR scans were performed pre-dose, and 1, 3, 7, 14 and 28 days after administration of C-ABC, and the signal intensity (SI) of the nucleus pulposus was measured. Radiographs were taken pre-dose, and 1, 2, 3, 4, 5, 6, 7, 14 and 28 days post-dose, to evaluate narrowing of the disk space in terms of height index (HI). In addition, the quantity of the chondroitin sulfate (CS) and the hyaluronic acid (HA) in the nucleus pulposus were measured by high performance liquid chromatography on day 28 after dosing. SI and HI continuously decreased, following the injection to 37.1% and 78.9% of the pre-dose values, respectively. Statistically significant differences (p<0.01) were observed between the C-ABC group and the control group in the respects on day 1 post-dose. CS and HA contents of the nucleus pulposus were noted to be significantly decreased on day 28 (p<0.01) in the treated group. This agent proved to degenerate proteoglycans in the nucleus pulposus, thus progressively reducing the interdiskal pressure from day 1 post-dose onwards. It is concluded that C-ABC is expected to afford its efficacy from early in the course of chemonucleolysis.
Macroscopic Hydrogels by Self-Assembly of Oligolactate-Grafted Dextran Microspheres (2007)

A novel approach is presented to create self-assembling hydrogels. Microspheres based on cross-linked dextran were chemically modified with L- or D-oligolactate chains. Successful grafting of the particles was confirmed by Fourier transform infrared (FT-IR) and Raman and X-ray photoelectron spectroscopy (XPS). Rheological analysis of aqueous dispersions of oligolactate-grafted microspheres demonstrated that hydrophobic interactions between oligolactate chains on the surface of various microspheres resulted in the formation of an almost fully elastic gel. A mixture of microspheres substituted with L- or D-oligolactates of opposite chirality resulted in gels with highest strength, likely due to stereocomplexation between the enantiomers. The network properties could be modulated by varying the solid content of the gel, the DS (i.e., number of lactate grafts per 100 glucopyranose units) and the DP (i.e., degree of polymerization) of the oligolactate grafts. Protein loading of the hydrogels could be achieved by simply mixing the microspheres with protein solution. Release experiments showed a continuous release of the entrapped lysozyme, with 50% released after 5 days and full preservation of its enzymatic activity. The biocompatible nature of the material, the protein-friendly self-assembly of the hydrogel and the possibility to tailor the gel properties, makes this hydrogel system an attractive candidate for pharmaceutical and biomedical applications.
Regional myocardial downregulation of the inhibitory guanosine triphosphate-binding protein (Gi alpha 2) and beta-adrenergic receptors in a porcine model of chronic episodic myocardial ischemia. (1993)

Regional myocardial ischemia is associated with increased levels of adenosine and norepinephrine, factors that may alter activation of the beta-adrenergic receptor (beta AR)-G protein-adenylyl cyclase pathway in the heart. We have used the ameroid constrictor model to determine whether alterations in myocardial signal transduction through the beta AR-G protein-adenylyl cyclase pathway occur in the setting of chronic episodes of reversible ischemia. Pigs were instrumented with ameroid occluders placed around the left circumflex coronary artery. 5 wk later, after ameroid closure, flow and function were normal in the ischemic bed, but flow (P = 0.001) and function (P < 0.03) were abnormal when metabolic demands were increased. The ischemic bed showed a reduction in myocardial beta AR number (P < 0.005). Despite regional downregulation of myocardial beta AR number, adenylyl cyclase activity was similar in the ischemic and control beds. Quantitative immunoblotting showed that the cardiac inhibitory GTP-binding protein, Gi alpha 2, was decreased in the ischemic bed (P = 0.02). In contrast, the cardiac stimulatory GTP-binding protein, Gs alpha, was increased in endocardial sections from the ischemic bed (P = < 0.05). Decreased Gi alpha 2 content was associated with decreased inhibition of adenylyl cyclase. Reduced Gi alpha 2 content, in conjunction with increased Gs alpha content in the endocardium, may provide a means by which adrenergic activation is maintained in the setting of chronic episodic myocardial ischemia.
The CMU MIDI Toolkit (1986)

The CMU MIDI Toolkit is a collection of programs for experimental computer music education, composition, performance, and research. The programs are intended to allow low-cost commercial synthesizers to be used in experimental and educational applications. The CMU MIDI Toolkit features a text-based score language and translator, a real-time programming environment, and it supports arbitrary tuning and rhythm. 1. Introduction and Overview The CMU MIDI Toolkit (CMT) is a software package designed for experimental computer music education, composition, performance, and research. CMT includes a compiler for a simple, text-based music language, and software for recording, playing, and computing MIDI data in real time. CMT has three major attractions: the flexibility of an open-ended design, the availability of source code, and low system cost. What does CMT do? The major components and their functions are described below: Adagio is a language and an associated compiler. In Adagio, a note ...
Structural Characteristics of the Nucleotide-Binding Site of Escherichia coli Primary Replicative Helicase DnaB Protein. Studies with Ribose and Base-Modified Fluorescent Nucleotide Analogs (1994)

Structural characteristics of the base- and ribose-binding regions of the high-affinity noninteracting nucleotide-binding site of Escherichia coli primary replicative helicase DnaB protein have been studied, using the base-modified fluorescent nucleotide analog 1, N6-ethenoadenosine diphosphate (epsilon ADP) and the ribose-modified fluorescent analogs 3'(2')-O-(N-methylantraniloyl)adenosine 5'-diphosphate (MANT-ADP), 3'-O-(N-methylantraniloyl)deoxyadenosine 5'-diphosphate (MANT-dADP), 3'-O-(N-methylantraniloyl)-deoxyadenosine 5'-triphosphate (MANT-dATP), and 2'(3')-O-(2,4,6-trinitrophenyl)adenosine 5'-diphosphate (TNP-ADP). The obtained data indicate contrasting differences between these two regions. Binding of epsilon ADP to the DnaB helicase causes only approximately 21% increase of the nucleotide fluorescence intensity and no shift of the emission spectrum maximum. The fluorescence of bound epsilon ADP is characterized by a single lifetime of 24.2 +/- 0.6 ns, only slightly shorter than the fluorescent lifetime of the free epsilon ADP in solution (25.5 +/- 0.6 ns). Solute-quenching studies of bound epsilon ADP, using different quenchers, acrylamide, I-, and Tl+, indicate limited accessibility of ethenoadenosine to the solvent. These results strongly suggest that the base-binding region of the DnaB nucleotide-binding site is located in the polar cleft on the enzyme's surface. Moreover, the limiting emission anisotropy of bound epsilon ADP is 0.21 +/- 0.02, compared to the anisotropy of 0.3 of completely immobilized epsilon ADP at the same excitation wavelength (lambda ex = 325 nm, lambda em = 410 nm), indicating that the adenine preserves substantial mobility when bound in the base-binding site. In contrast, fluorescence intensity at the emission maximum of TNP-ADP and MANT-ADP, which has modifying groups attached to the 2' and/or 3' oxygens of the ribose, increases upon binding to DnaB by factors of approximately 4.7 (lambda ex = 408 nm) and approximately 2.6 (lambda ex = 356 nm), respectively. Moreover, the maximum of emission spectrum of bound TNP-ADP is blue-shifted by approximately 11 nm and that of MANT-ADP by approximately 12 nm. Comparisons between spectral properties of TNP-ADP and MANT-ADP bound to DnaB and in different solvents suggest that the ribose-binding region of the DnaB nucleotide-binding site has relatively low polarity. Solute quenching studies of MANT-ADP fluorescence, using acrylamide, I-, and Tl+, indicate that the MANT group has very little accessibility to the solvent when bound to DnaB. Taken together, these results suggest that the ribose-binding region constitutes a hydrophobic cleft, or pocket, with very limited, if any, contact with the solvent.(ABSTRACT TRUNCATED AT 400 WORDS)
Intravenous plasmin-treated gammaglobulin therapy in idiopathic thrombocytopenic purpura. Results in 40 patients. (1985)

A study of the effects of high-dose IV plasmin-treated IgG was undertaken in 40 patients (30 children and 10 adults) with idiopathic thrombocytopenic purpura (ITP). After a first course of treatment, a success therapy (platelet counts greater than 100 X 10(9)/l) was observed in 21 patients. The results after additional courses of pH 4 treated IgG in 7 patients tended to indicate that the 2 kinds of concentrates might induce similar platelet responses. No significant side-effects were observed. Platelet associated (PA), IgG, IgM and C3 levels were determined before therapy and on the 7th day after the first infusion (day 8) in 27 patients (36 courses). In spite of great variability, overall results showed a significant decrease in PA IgG (P less than 0.05), PA IgM (P less than 0.01) and PA C3 (P less than 0.001) at day 8. A significant inverse relationship was found between either PA IgG, or PA IgM or PA C3 levels, and platelets counts (respectively, r = -0.57, -0.55, -0.66, P less than 0.001). Our results also showed that pretreatment platelet counts were higher in patients with success therapy (25.8 +/- 16.9 X 10(9)/l) than in others (11.3 +/- 12.1 X 10(9)/l, P less than 0.001). This suggested that pretreatment platelet counts could help predicting the platelet response.
Disodium Cromoglycate Relieves Symptoms in Symptomatic Young Smokers (1984)

We have undertaken a double blind placebo controlled study of disodium cromoglycate (DSCG) in 32 symptomatic young smokers. These individuals had regular morning cough and sputum with the sensation of wheeze, but were not asthmatics as determined by the usual criteria. No significant changes were observed in sputum or serum eosinophils, IgE, IgG or IgA, or sputum histamine concentrations following the administration, for 3 weeks, of either DSCG (20 mg) or placebo, thrice daily. However DSCG, but not placebo, was associated with significant improvements in the symptoms of cough (P less than 0.01) and wheezing (P less than 0.025). We suggest that these changes may be due to an effect of DSCG on the irritant receptor mediated reflex response to cigarette smoke rather than the involvement of mast cells.
Interleukin 15 Controls both Proliferation and Survival of a Subset of Memory-Phenotype CD8+ T Cells (2002)

Previous work has shown that memory-phenotype CD44(hi) CD8(+) cells are controlled by a cytokine, interleukin (IL)-15. However, the dependency of CD44(hi) CD8(+) cells on IL-15 is partial rather than complete. Here, evidence is presented that CD44(hi) CD8(+) cells comprise a mixed population of IL-15-dependent and IL-15-independent cells. The major subset of CD122(hi) CD44(hi) CD8(+) cells is heavily dependent on IL-15 by three different parameters, namely (1) "bystander" proliferation induced via IFN-induced stimulation of the innate immune system, (2) normal "background" proliferation, and (3) T cell survival; IL-15 dependency is most extreme for the Ly49(+) subset of CD122(hi) CD44(hi) CD8(+) cells. In contrast to CD122(hi) cells, the CD122(lo) subset of CD44(hi) CD8(+) cells is IL-15 independent; likewise, being CD122(lo), CD44(hi) CD4(+) cells are IL-15 independent. Thus, subsets of memory-phenotype T cells differ radically in their sensitivity to IL-15.
Properties of the telomeric DNA-binding protein from Oxytricha nova (1989)

Telomeres of Oxytricha macronuclear DNA exist as discrete DNA-protein complexes. Different regions of each complex display characteristic DNA-protein interactions. In the most terminal region, binding of a 43- and a 55-kDa protein to the telomeric DNA appears to account for all the DNA-protein interactions that can be detected by chemical and nuclease footprinting. We have used gradient sedimentation and protein-protein cross-linking to establish that the 43- and 55-kDa proteins are subunits of a heterodimer. Both subunits are very basic, which is unexpected considering the resistance of the DNA-protein interaction to high concentrations of salt. It is extremely difficult to dissociate the two subunits either from telomeric DNA or from each other. Even after extensive treatment of protein preparations with nuclease, a fragment of the 3' tail from macronuclear DNA remains bound to the protein. A wide range of conditions was screened for dissociation of the subunits from the DNA and/or from each other. Dissociation was only obtained by using conditions that caused some inactivation of the DNA-binding capacity of the protein. The use of reagents that covalently modify sulfydryl groups during the purification procedure facilitates preparation of telomere protein with full DNA-binding activity.
Dynamic Changes in Binding of Immunoglobulin Heavy Chain 3′ Regulatory Region to Protein Factors during Class Switching (2011)

The 3' regulatory region (3' RR) of the Igh locus works at long distances on variable region (V(H)) and switch region (I) region promoters to initiate germ line (non-coding) transcription (GT) and promote class switch recombination (CSR). The 3' RR contains multiple elements, including enhancers (hs3a, hs1.2, hs3b, and hs4) and a proposed insulator region containing CTCF (CCCTC-binding factor) binding sites, i.e. hs5/6/7 and the downstream region ("38"). Notably, deletion of each individual enhancer (hs3a-hs4) has no significant phenotypic consequence, suggesting that the 3' RR has considerable structural flexibility in its function. To better understand how the 3' RR functions, we identified transcription factor binding sites and used chromatin immunoprecipitation (ChIP) assays to monitor their occupancy in splenic B cells that initiate GT and undergo CSR (LPS±IL4), are deficient in GT and CSR (p50(-/-)), or do not undergo CSR despite efficient GT (anti-IgM+IL4). Like 3' RR enhancers, hs5-7 and the 38 region were observed to contain multiple Pax5 binding sites (in addition to multiple CTCF sites). We found that the Pax5 binding profile to the 3' RR dynamically changed during CSR independent of the specific isotype to which switching was induced, and binding focused on hs1.2, hs4, and hs7. CTCF-associated and CTCF-independent cohesin interactions were also identified. Our observations are consistent with a scaffold model in which a platform of active protein complexes capable of facilitating GT and CSR can be formed by varying constellations of 3' RR elements.
α-Enolase Expressed on the Surfaces of Monocytes and Macrophages Induces Robust Synovial Inflammation in Rheumatoid Arthritis (2012)

α-Enolase (ENO1) is a multifunctional glycolytic enzyme expressed abundantly in the cytosol. It has been implicated in autoimmune and inflammatory diseases. Serum Abs against ENO1 were reported in rheumatoid arthritis (RA). Cell-surface expression of ENO1 has been found to be increased rapidly in response to inflammatory stimuli, but its expression and function has not been reported in RA. In this study, we show that cell-surface expression of ENO1 is increased on monocytes and macrophages isolated from RA patients but not on those from osteoarthritis patients, and Ab against ENO1 can stimulate these cells to produce higher amounts of proinflammatory mediators, such as TNF-α, IL-1 α/β, IFN-γ, and PGE(2) via p38 MAPK and NF-κB pathway. The frequency of ENO1-positive cells in synovial fluid mononuclear cells was higher than PBMCs. ENO1-positive cells were also found in the inflamed synovium from RA patients and arthritic ankle tissues of mice with collagen-induced arthritis. Taken together, these findings suggest that Abs against ENO1 present in RA sera may stimulate monocytes and macrophages expressing cell-surface ENO1 and contribute to production of proinflammatory mediators during the effector phase of synovial inflammation.
Subretinal Microelectrode Arrays Allow Blind Retinitis Pigmentosa Patients to Recognize Letters and Combine them to Words (2009)

Eleven patients received subretinal implants, powered and controlled via a subdermal cable ending in a thin intraocular foil, placed transsclerally between the retinal pigment epithelium and the neuroretina. The tip of this foil carries two distinct arrays, a Multiphotodiode Array (MPDA) with 1500 electrodes, each electrode being controlled by an adjacent photodiode and an amplifier within a 3times3times0.1 mm chip, as well as a second array with 16 electrodes, for direct stimulation (DS). Subretinal multielectrode implants with currents close to recognition threshold (10 to 27 nC/electrode) produce retinotopically correct patterns that allow for the first time recognition of individual letters (8 cm high, viewed in appr. 62 cm distance) even at low luminance levels. Stripe patterns of moderate luminance can be resolved up to 0.35 cycles/deg via the subretinal chip. This clearly supports the feasibility of light sensitive subretinal multielectrode devices for restoration of useful visual percepts in blind patients.
HHsenser: exhaustive transitive profile search using HMM-HMM comparison (2006)

HHsenser is the first server to offer exhaustive intermediate profile searches, which it combines with pairwise comparison of hidden Markov models. Starting from a single protein sequence or a multiple alignment, it can iteratively explore whole superfamilies, producing few or no false positives. The output is a multiple alignment of all detected homologs. HHsenser's sensitivity should make it a useful tool for evolutionary studies. It may also aid applications that rely on diverse multiple sequence alignments as input, such as homology-based structure and function prediction, or the determination of functional residues by conservation scoring and functional subtyping.HHsenser can be accessed at http://hhsenser.tuebingen.mpg.de/. It has also been integrated into our structure and function prediction server HHpred (http://hhpred.tuebingen.mpg.de/) to improve predictions for near-singleton sequences.