gebhart/patrepeval huggingface dataset:
Lens epithelium-derived growth factor: increased survival and decreased DNA breakage of human RPE cells induced by oxidative stress. (2001)

LEDGF enhanced survival of RPE cells in culture when challenged by oxidative stress and UVB irradiation. LEDGF protected DNA from single-strand breakage and upregulated the expression of Hsp27. These results suggest that LEDGF may be a potential agent for protecting RPE cells under various stress conditions.
Mechanisms for the pleiotropic effects of the agouti gene. (1995)

The agouti locus is one of several classic genetic loci that affect the coat color of mice. The wild-type agouti phenotype, exemplified by dorsal coat hairs that are black with a single subapical band of yellow and lighter-colored ventral hairs, is found in many mammals including animals of the genera Mus (mice), Oryctolagus (rabbits), Sciurus (squirrels), and Canis (wolves) (reviewed in ref. 1). Much interest has focused on the agouti gene because several dominant mutations result in mice that exhibit adult onset obesity, hyperinsulinemia, and' noninsulindependent diabetes. In addition, mice carrying dominant agouti mutations show an increased susceptibility to a variety of spontaneous and/or induced solid tumors. These mutations provide potential animal models of human disease, and the mouse provides an organism amenable to molecular genetic, biochemical, physiological, and pharmacological manipulations to investigate the causes and treatments of these diseases. The mechanism of action of the agouti gene in all of these phenotypes is under intense investigation. Several recent papers including two in this issue by Klebig et al (2) and Zemel et al (3) now shed light on some modes of action of the agouti protein as well as provide models for in vivo and in vitro tests of agouti function.
Novel Detection Method of Nitric Oxide Using Horseradish Peroxidase. (1996)

Nitric oxide (NO) readily makes corresponding complexes not only with ferrous iron but also with ferric iron. However, NO-ferric complexes of many heme proteins were unstable, while horseradish peroxidase formed the very stable NO-ferric porphyrin complex with a shift of the Soret band of the absorption wavelength from 396.5 nm to 420.0 nm. The concentration of NO in aqueous media could be monitored by measuring the absorption changes, and the detection limit was 10 nM. The simple procedure is convenient for concentration determination of NO solution.
Record High Hole Mobility in Polymer Semiconductors via Side-Chain Engineering (2013)

Charge carrier mobility is still the most challenging issue that should be overcome to realize everyday organic electronics in the near future. In this Communication, we show that introducing smart side-chain engineering to polymer semiconductors can facilitate intermolecular electronic communication. Two new polymers, P-29-DPPDBTE and P-29-DPPDTSE, which consist of a highly conductive diketopyrrolopyrrole backbone and an extended branching-position-adjusted side chain, showed unprecedented record high hole mobility of 12 cm(2)/(V·s). From photophysical and structural studies, we found that moving the branching position of the side chain away from the backbone of these polymers resulted in increased intermolecular interactions with extremely short π-π stacking distances, without compromising solubility of the polymers. As a result, high hole mobility could be achieved even in devices fabricated using the polymers at room temperature.
Polymerized pickering HIPEs: Effects of synthesis parameters on porous structure (2010)

Abstract A polyHIPE is a highly porous polymer synthesized from monomers within the external phase of a high internal phase emulsion (HIPE). The large amount of difficult to remove surfactant needed for HIPE stabilization can affect the properties of the resulting polymer. A Pickering emulsion is a surfactant‐free emulsion stabilized by solid particles that preferentially migrate to the interface. In this article, the synthesis of crosslinked polyacrylate polyHIPEs based on Pickering HIPEs stabilized using silane‐modified silica nanoparticles is described and the effects of the synthesis parameters on the porous structure are discussed. The silane chemistry, silane content, and nanoparticle content had significant effects on the size of the polyhedral, relatively closed‐cell polyHIPE voids that resulted from aqueous‐phase initiation. Increasing the mixing intensity reduced the wall thickness and produced a more open‐cell structure. The locus of initiation had a significant effect on polyHIPE morphology. Organic‐phase initiation yielded larger, more spherical voids from the more extensive coalescence before the structure could be “locked‐in” at the gel point. Most significantly, the nanoparticles were located within the polymer walls rather than at the interface, as might be expected. The void walls were shown to be an assembly of nanoparticle agglomerate shells that become embedded within the polymer. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1516–1525, 2010
Butyrate inhibits interleukin-17 and generates Tregs to ameliorate colorectal colitis in rats (2016)

Our results suggest that butyrate plays a key role in regulating the Treg/Th17 balance and ultimately protects the colon mucosa against the development of IBD.
Release of Thioredoxin via the Mechanosensitive Channel MscL during Osmotic Downshock of Escherichia coli Cells (1998)

Escherichia coli cells possess several mechanosensitive ion channels but only MscL, the channel with the highest conductance, which is activated at the highest membrane tension, has been cloned. We investigated the putative involvement of MscL in the effluxes caused by osmotic downshock. Osmotic shock caused the release of potassium glutamate, trehalose, and glycine betaine from wild type cells and cells lacking MscL. There was no difference between the two strains, but the extreme rapidity of the efflux process, as shown herein for glycine betaine, suggests that it is channel-mediated. Osmotic downshock also induces the release of some cytosolic proteins from EDTA-treated cells. We investigated the release of thioredoxin. This protein was totally released from wild type cells but was retained by MscL- cells. Release was restored by expression of the gene coding for MscL. Thus MscL is not necessary for the excretion of osmoprotectants, but it does open in vivo during shock and catalyzes the efflux of thioredoxin and possibly other small cytosolic proteins. It follows that the other mechanosensitive channels, which are known to be activated at lower tension, must also open during osmotic shock. Their opening and that of MscL could account for the rapid release of osmolytes.
The modified Julia olefination: alkene synthesis via the condensation of metallated heteroarylalkylsulfones with carbonyl compounds (2002)

Covering: until May 2002.
Integrated fluid handling system for biomolecular interaction analysis (1991)

An integrated fluid handling system used for multichannel biomolecular interaction analysis is described. Reactions between biological molecules are monitored in real time by measuring changes in the angular position where surface plasmon resonance occurs at a biospecific active surface. The adsorption efficiency of the analyte onto the biospecific active surface is up to approximately 3%, due to the low channel height, 50 microns, in the flow cell. When a large part of the total biospecific active surface for surface plasmon resonance probing (approximately 0.15 mm2) is used, the sensitivity is high. Sample sizes in the order of 1-50 microL can be injected. The sample zone dispersion is minimized by the low dead volume in the system (approximately 0.4 microL) accomplished by using integrated sample loops and thin conduits. An asset of this integration is the low reagent consumption. The sensor chip with the biospecific active surface is reusable and easily exchanged. Experimental results obtained with a theophylline monoclonal antibody as the analyte are compared with a theoretical model. The standard deviation for the repeatability is approximately 5% typically with 50 microL of 250 pM analyte, and the assay time is 10 min. The detection limit is approximately 10 pg of the analyte on the probed spot of the surface. Possible improvements of the sensitivity and detection limit are discussed.
Abstract B212: QTc study of picoplatin with emphasis on pharmacodynamics of cardiac repolarization (2009)

Abstract Introduction: Clinical studies have demonstrated that picoplatin (Pico), a new-generation platinum analogue designed to overcome platinum resistance, has activity when administered IV in solid tumors patients (pts); over 1,100 pts have received pico. The primary toxicity is hematological. Clinically significant nephro-, oto-, or neurotoxicity has rarely been observed (&amp;lt;1% grade 3 and 0% grade 4), even in platinum-pretreated patients. Pico (150 mg/m2) Q3W is currently being studied in a Phase 3 trial as 2nd-line monotherapy for SCLC. Pico is also being studied in Phase 2 trials in combination with other chemotherapy drugs for colorectal and prostate cancers. In preclinical studies in dogs, pico had no effect on cardiovascular function, including the QT interval. In clinical trials to date, drug-related serious ventricular arrhythmias have not been observed. The purpose of this study was to assess cardiac effects of Pico in patients with advanced solid tumors. Methods: The effect of pico on the QT/QTc interval as measured by the ECG was evaluated. The correlation between the QTcF interval and platinum concentration in plasma and plasma ultrafiltrate (PUF) was evaluated. ECG was recorded continuously with a Holter monitor. Triplicate 20 second ECG readings were extracted at 3 times before (baseline reference) and at 8 times in the 24 hrs after pico administration in Cycle 1. Triplicate 12-lead ECGs were obtained at the end of the pico infusion in subsequent cycles. Blood samples were collected before study drug administration and immediately after each ECG timepoint in Cycle 1 for pharmacokinetic analysis. The primary endpoint was the Fredericia corrected QT (QTcF). Time-averaged and time point analyses for QTcF were performed. Heart rate, PR, QRS, QT, QTcB (Bazett's) and morphological changes were also evaluated. Results: 45 pts (28 women and 17 men), age 44–79 years (median = 60) received 150 mg/m2 pico as a 1-hr IV infusion. The time-averaged mean change from baseline of QTcF duration during Cycle 1 was +2.2 ms, which is considered a nonsignificant increase. At each time point in Cycle 1 and in subsequent cycles, there were only minimal changes from baseline in QTcF duration. Other ECG changes from baseline were unremarkable: ST depression was noted in 9% of pts at baseline and new T-wave changes in 7% of pts in Cycle 1. Mean ± SD Cmax in plasma and PUF were 5566 ± 1079 ng/mL and 4034 ± 674 ng/mL, respectively. The change in QTcF vs. platinum concentration in plasma or PUF showed a Cmax effect of 5–6 ms with an upper confidence interval of 8–9 ms, suggesting no clear effect of picoplatin on QTcF. Conclusions: Pico had no effect on the QTcF interval or any other ECG parameter, supporting the clinical data showing that Pico does not increase the risk of serious ventricular arrhythmias. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B212.
Deletion of Mouse Rad9 Causes Abnormal Cellular Responses to DNA Damage, Genomic Instability, and Embryonic Lethality (2004)

The fission yeast Schizosaccharomyces pombe rad9 gene promotes cell survival through activation of cell cycle checkpoints induced by DNA damage. Mouse embryonic stem cells with a targeted deletion of Mrad9, the mouse ortholog of this gene, were created to evaluate its function in mammals. Mrad9(-/-) cells demonstrated a marked increase in spontaneous chromosome aberrations and HPRT mutations, indicating a role in the maintenance of genomic integrity. These cells were also extremely sensitive to UV light, gamma rays, and hydroxyurea, and heterozygotes were somewhat sensitive to the last two agents relative to Mrad9(+/+) controls. Mrad9(-/-) cells could initiate but not maintain gamma-ray-induced G(2) delay and retained the ability to delay DNA synthesis rapidly after UV irradiation, suggesting that checkpoint abnormalities contribute little to the radiosensitivity observed. Ectopic expression of Mrad9 or human HRAD9 complemented Mrad9(-/-) cell defects, indicating that the gene has radioresponse and genomic maintenance functions that are evolutionarily conserved. Mrad9(+/-) mice were generated, but heterozygous intercrosses failed to yield Mrad9(-/-) pups, since embryos died at midgestation. Furthermore, Mrad9(-/-) mouse embryo fibroblasts were not viable. These investigations establish Mrad9 as a key mammalian genetic element of pathways that regulate the cellular response to DNA damage, maintenance of genomic integrity, and proper embryonic development.
Enhanced 5-methylcytosine detection in single-molecule, real-time sequencing via Tet1 oxidation (2013)

We have developed a method for the enhancement of directly detecting 5-methylcytosine during single-molecule, real-time sequencing. Using Tet1 to convert 5-methylcytosine to 5-carboxylcytosine improves the detection rate of this important epigenetic marker, thereby complementing the set of readily detectable microbial base modifications, and enhancing the ability to interrogate eukaryotic epigenetic markers.
SpliceDB: database of canonical and non-canonical mammalian splice sites (2001)

A database (SpliceDB) of known mammalian splice site sequences has been developed. We extracted 43 337 splice pairs from mammalian divisions of the gene-centered Infogene database, including sites from incomplete or alternatively spliced genes. Known EST sequences supported 22 815 of them. After discarding sequences with putative errors and ambiguous location of splice junctions the verified dataset includes 22 489 entries. Of these, 98.71% contain canonical GT-AG junctions (22 199 entries) and 0.56% have non-canonical GC-AG splice site pairs. The remainder (0.73%) occurs in a lot of small groups (with a maximum size of 0.05%). We especially studied non-canonical splice sites, which comprise 3.73% of GenBank annotated splice pairs. EST alignments allowed us to verify only the exonic part of splice sites. To check the conservative dinucleotides we compared sequences of human non-canonical splice sites with sequences from the high throughput genome sequencing project (HTG). Out of 171 human non-canonical and EST-supported splice pairs, 156 (91.23%) had a clear match in the human HTG. They can be classified after sequence analysis as: 79 GC-AG pairs (of which one was an error that corrected to GC-AG), 61 errors corrected to GT-AG canonical pairs, six AT-AC pairs (of which two were errors corrected to AT-AC), one case was produced from a non-existent intron, seven cases were found in HTG that were deposited to GenBank and finally there were only two other cases left of supported non-canonical splice pairs. The information about verified splice site sequences for canonical and non-canonical sites is presented in SpliceDB with the supporting evidence. We also built weight matrices for the major splice groups, which can be incorporated into gene prediction programs. SpliceDB is available at the computational genomic Web server of the Sanger Centre: http://genomic.sanger.ac. uk/spldb/SpliceDB.html and at http://www.softberry. com/spldb/SpliceDB.html.
PACAP and its receptor VPAC1 regulate megakaryocyte maturation: therapeutic implications (2007)

Megakaryocytes and platelets express the Gs-coupled VPAC1 receptor, for which the pituitary adenylyl cyclase-activating peptide (PACAP) and the vasointestinal peptide (VIP) are agonists. We here demonstrate a regulatory role for VPAC1 signaling during megakaryopoiesis. A total of 2 patients with trisomy 18p with PACAP overexpression and transgenic mice overexpressing PACAP in megakaryocytes have thrombopathy, a mild thrombocytopenia, and a reduced number of mature megakaryocytes in their bone marrow. In vitro differentiation of hematopoietic stem cells from the patient and transgenic mice shows a reduced number of megakaryocyte colonies compared with controls. The addition of PACAP, VIP, or the adenylyl cyclase activator forskolin to CD34(+) cells inhibits megakaryocyte differentiation. In contrast, neutralizing monoclonal anti-PACAP (PP1A4) or anti-VPAC1 (23A11) antibodies inhibit cAMP formation and stimulate megakaryopoiesis in a thrombopoietin-independent manner. Moreover, wild-type mice obtain an increased platelet count after subcutaneous injection of PP1A4 or 23A11. These antibodies also elevate platelet numbers in animal models of myelosuppressive therapy and in GATA1-deficient mice with congenital thrombocytopenia. Furthermore, 23A11 stimulates the in vitro megakaryocyte differentiation of both normal and GATA1-deficient human CD34(+) cells. Together, our data strongly suggest that VPAC1 signaling tempers normal megakaryopoiesis, and that inhibition of this pathway stimulates megakaryocyte differentiation, enhancing platelet recovery after myelosuppressive therapy and in GATA1 deficiency.
ABO, D Blood Typing and Subtyping Using Plug-Based Microfluidics (2008)

A plug-based microfluidic approach was used to perform multiple agglutination assays in parallel without cross-contamination and using only microliter volumes of blood. To perform agglutination assays on-chip, a microfluidic device was designed to combine aqueous streams of antibody, buffer, and red blood cells (RBCs) to form droplets 30-40 nL in volume surrounded by a fluorinated carrier fluid. Using this approach, proof-of-concept ABO and D (Rh) blood typing and group A subtyping were successfully performed by screening against multiple antigens without cross-contamination. On-chip subtyping distinguished common A1 and A2 RBCs by using a lectin-based dilution assay. This flexible platform was extended to differentiate rare, weakly agglutinating RBCs of A subtypes by analyzing agglutination avidity as a function of shear rate. Quantitative analysis of changes in contrast within plugs revealed subtleties in agglutination kinetics and enabled characterization of agglutination of rare blood subtypes. Finally, this platform was used to detect bacteria, demonstrating the potential usefulness of this assay in detecting sepsis and the potential for applications in agglutination-based viral detection. The speed, control, and minimal sample consumption provided by this technology present an advance for point of care applications, blood typing of newborns, and general blood assays in small model organisms.
Calculus revisited (1986)

Although there is no doubt that gingivitis can develop in the absence of supragingival calculus, it is not clear to what extent the presence of mineralized deposit enhances gingival inflammation. Partial inhibition of plaque mineralization can be accomplished by chemical agents, but there has been no demonstration in humans of a reduction in gingivitis. It remains to be established what level of inhibition (if any) is required to have more than a cosmetic effect. Since the accepted scenario is that apical growth of supragingival plaque precedes the formation of subgingival calculus, there is no longer an issue of whether subgingival calculus is the cause or the result of periodontal disease. Subgingival mineralization results from the interaction of subgingival plaque with the influx of mineral salts that is part of the serum transudate and inflammatory exudate. This chronology, however, should not be the basis for relegating calculus to the ash heap. Morphologic and analytical studies point to the porosity of calculus and retention of bacterial antigens and the presence of readily available toxic stimulators of bone resorption. When coupled with the increased build up of plaque on the surface of the calculus, the combination has the potential for extending (beyond that of plaque alone) the radius of destruction and the rate of displacement of the adjacent junctional epithelium. The centrality of thorough scaling and root planing in the successful maintenance of periodontal health supports the view that subgingival calculus contributes significantly to the chronicity and progression of the disease, even if it can no longer be considered as responsible for initiation.
Formation of high molecular weight complexes of mutant Cu,Zn-superoxide dismutase in a mouse model for familial amyotrophic lateral sclerosis (2000)

Deposition of aggregated protein into neurofilament-rich cytoplasmic inclusion bodies is a common cytopathological feature of neurodegenerative disease. How-or indeed whether-protein aggregation and inclusion body formation cause neurotoxicity are presently unknown. Here, we show that the capacity of superoxide dismutase (SOD) to aggregate into biochemically distinct, high molecular weight, insoluble protein complexes (IPCs) is a gain of function associated with mutations linked to autosomal dominant familial amyotrophic lateral sclerosis. SOD IPCs are detectable in spinal cord extracts from transgenic mice expressing mutant SOD several months before inclusion bodies and motor neuron pathology are apparent. Sequestration of mutant SOD into cytoplasmic inclusion bodies resembling aggresomes requires retrograde transport on microtubules. These data indicate that aggregation and inclusion body formation are mechanistically and temporally distinct processes.
Isolation and characterization of the methionine aminopeptidase from porcine liver responsible for the co-translational processing of proteins. (1992)

A methionine aminopeptidase that specifically removes methionine residues from peptides with amino-terminal sequences of Met-Ala-, Met-Val-, Met-Ser-, Met-Gly-, and Met-Pro- but not Met-Leu- or Met-Lys- has been isolated to homogeneity from porcine liver by a procedure involving five chromatographic steps. The enzyme, whose specificity matches that predicted for the entity responsible for the co-translational amino-terminal processing of nascent polypeptide chains, has a measured molecular mass of 70,000 Da by SDS-polyacrylamide electrophoresis and 67,000 Da by gel chromatography (under nondenaturing conditions), suggesting the native molecule is a monomer. It is activated by Co2+ and inhibited by beta-mercaptoethanol and EDTA. With octapeptide substrates related to the amino-terminal portion of the beta-chain of human hemoglobin (with a histidine in position 3), the enzyme had a pH optimum of 6.0. With a synthetic peptide devoid of histidine, it showed no pH dependence from 6.0 to 8.0. This sensitivity may be due to the propensity of peptides with histidine in the third position to bind divalent cations such as Co2+. The measured Km and kappa cat values were affected by residues in the second position. The peptide corresponding to the natural sequence (Met-Val-His-) gave a kappa cat/Km value of 260 mM-1 s-1; substitution of alanine in the second position raised the kappa cat/Km to 1523 mM-1 s-1, but substitution of proline lowered the value to 130. The effects are primarily on the kappa cat. The substitution of proline (for histidine) in the third position, the mutation found in hemoglobin Long Island, prevents the removal of the methionine residue, as occurs with the mutant protein. The porcine liver enzyme is similar to methionine aminopeptidases isolated from Escherichia coli, Salmonella typhimurium, and yeast in that it also is stimulated by Co2+. However, it is much larger than these enzymes and differs somewhat in specificity, particularly with the yeast enzyme.