gebhart/patrepeval huggingface dataset:
Anticonvulsant activity of a nonpeptide galanin receptor agonist (2002)

Galanin is a neuropeptide with a wide variety of biological functions, including that of a strong endogenous anticonvulsant. No nonpeptide ligands, capable of activating galanin receptors, are available today. Based on known pharmacophores of galanin, a combinatorial library was designed, synthesized, and screened at the rat hippocampal galanin receptor. A low molecular weight galanin receptor agonist, 7-((9-fluorenylmethoxycarbonyl)cyclohexylalanyllysyl)amino-4-methylcoumarin (galnon) was found to displace (125)I-galanin with micromolar affinity at Bowes cellular and rat hippocampal membranes. Autoradiographic binding assay on rat spinal cord sections confirmed the ability of galnon to displace (125)I-galanin from its binding sites. Galnon inhibited adenylate cyclase activity, suggesting an agonist action at galanin receptors. When injected i.p. galnon reduced the severity and increased the latency of pentylenetetrazole-induced seizures in mice and reversed the proconvulsant effects of the galanin receptor antagonist M35, injected into a lateral ventricle. Intrahippocampal injection of galnon also shortened the duration of self-sustaining status epilepticus in rats, confirming its agonist properties in vivo. Pretreatment of rats with antisense peptide nucleic acid targeted to galanin receptor type 1 mRNA abolished the effect of galnon, suggesting mediation of its anticonvulsant properties through this receptor subtype. These findings introduce a systemically active nonpeptide galanin agonist anticonvulsant.
Biochemical studies on bovine adenovirus type 3. III. Cleavage maps of viral DNA by restriction endoncleases EcoRI, BamHI, and HindIII (1978)

Cleavage of bovine adenovirus type 3 (BAV3) DNA by restriction endonucleases EcoRI, BamHI, and HindIII yielded 7 (A to G), 5 (A to E), and 12 (A to L) fragments, respectively. The order of these fragments has been determined to be GDACBFE for EcoRI fragments, AEBDC for BamHI fragments, and JEBKACDHFGIL for HindIII fragments, and cleavage sites of these enzymes have been mapped on the genome of BAV3. BAV3 preparation contains incomplete virus whose genome has a deletion of about 13% of complete virus genome. Restriction endonuclease digestion of the incomplete virus DNA revealed that EcoRI E and F, BamHI C and HindIII G, I, and L fragments were deleted. Therefore, the deleted region of incomplete virus DNA is located near the right-hand end of the BAV3 DNA molecule, a result consistent with our previous electron-microscopic observations on heteroduplex molecules formed between complete and incomplete BAV3 DNA.
Human β-Mannosidase Deficiency (1986)

LYSOSOMAL disorders in humans due to deficiencies of lysosomal enzymes or effector proteins (activator or protector proteins) have been described for most steps in the catabolism of glycoproteins, glycolipids, and glycosaminoglycans (mucopolysaccharides).1 2 3 A deficiency of one of these enzymes or proteins usually results in the accumulation of undegraded storage products (some primary and others secondary to the defect), and this leads to most of the clinical features observed in the patients. Disorders affecting the catabolism of the oligosaccharide portion of glycoproteins, such as sialidosis, GM1 gangliosidosis, α-mannosidosis, Sandhoff's disease, fucosidosis, and aspartylglycosaminuria have been described previously.1 , 2 The enzyme defects . . .
DC-Link ripple reduction of series-connected module integrated converter for Photovoltaic systems (2011)

Recently, Building Integrated Photovoltaic (BIPV) generation systems have been studied in renewable energy engineering Held because the systems require small space installation and a reduced building material cost in spite of the performance degradation from partial shading. In case of a MIC with series connected output, it is easy to obtain a high DC-Link voltage for grid-connected applications. However, DC-Link voltage ripple also increases as the number of modules increases. In this paper, as a manner of ripple reduction, interleaved control method is applied to the PV MIC modules. For the implementation of the phase synchronization, Zigbee (Xbee-pro) wireless communications transceiver and DSP's Series Communications Interface are utilized. A 80W hardware prototype two boost-type of MIC is built to verify the DC Link voltage ripple reduction.
Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse (2010)

As reported with other surfactants, the surfactant/emulsifier GML markedly increased susceptibility to HSV-2. Glycerin at 30% significantly increased susceptibility, and, undiluted propylene glycol and PEG-8 greatly increased susceptibility.
Reperfusion-Activated Akt Kinase Prevents Apoptosis in Transgenic Mouse Hearts Overexpressing Insulin-Like Growth Factor-1 (2001)

Abstract -Hearts of wild-type and insulin-like growth factor-1 overexpressing (Igf-1(+/-)) transgenic mice were subjected to Langendorff perfusions and progressive periods of ischemia followed by reperfusion. Apoptosis was measured by DNA nucleosomal cleavage and a hairpin probe labeling assay to detect single-base overhang. Transgenic hearts subjected to 20 minutes of ischemia and 4 hours of reperfusion (I/R) sustained a rate of apoptosis of 1.8+/-0.3% compared with 4.6+/-1.1% for wild-type controls (n=4; P<0.03). Phosphorylation of the protein kinase Akt/protein kinase B was elevated 6.2-fold in transgenic hearts at baseline and increased another 4.4-fold within 10 minutes of reperfusion, remaining elevated for up to 2 hours. I/R activated Akt in wild-type hearts but to a lesser extent (1.6+/-0.3-fold). Pretreatment of transgenic hearts with wortmannin immediately before and during ischemia eliminated reperfusion-mediated activation of Akt and neutralized the resistance to apoptosis. The stress-activated kinase p38 was also activated during ischemia and reperfusion in both wild-type and transgenic hearts. Perfusion with the p38 inhibitor SB203580 (10 micromol/L) blocked both p38 activation and phosphorylation of Akt and differentially modulated apoptosis in wild-type and transgenic hearts. Pretreatment with SB203580 reduced apoptosis in wild-type hearts but increased apoptosis in transgenic hearts. These results demonstrate that Akt phosphorylation during I/R is modulated by IGF-1 and prevents apoptosis in hearts that overexpress the IGF-1 transgene.
Audio-visual speech recognition (2000)

We have made signi cant progress in automatic speech recognition ASR for well-de ned applications like dictation and medium vocabulary transaction processing tasks in relatively controlled environments.However, for ASR to approach h uman levels of performance and for speech to become a truly pervasive user interface, we need novel, nontraditional approaches that have the potential of yielding dramatic ASR improvements.Visual speech is one such source for making large improvements in high noise environments with the potential of channel and task independence.It is not e ected by the acoustic environment and noise, and it possibly contains the greatest amount of complementary information to the acoustic signal.In this workshop, our goal was to advance the state-of-the-art in ASR by demonstrating the use of visual information in addition to the traditional audio for large vocabulary continuous speech recognition LVCSR.Starting with an appropriate audio-visual database, collected and provided by IBM, we demonstrated for the rst time that LVCSR performance can be improved by the use of visual information in the clean audio case.Speci cally, b y conducting audio lattice rescoring experiments, we showed a 7 relative word error rate WER reduction in that condition.Furthermore, for the harder problem of speech contaminated by s p e e c h babble" noise at 10 dB SNR, we demonstrated that recognition performance can beimproved by 27 in relative WER reduction, compared to an equivalent audio-only recognizer matched to the noise environment.We believe that this paves the way to seriously address the challenge of speech recognition in high noise environments and to potentially achieve human levels of performance.In this report, we detail a number of approaches and experiments conducted during the summer workshop in the areas of visual feature extraction, hidden Markov model based visual-only recognition, and audio-visual information fusion.The later was our main concentration: In the workshop, a numberof feature fusion as well as decision fusion techniques for audio-visual ASR were explored and compared.
Hyperbilirubinemia in Low Birth Weight Infants and Outcome at 5 Years of Age (1992)

The collaborative national survey on morbidity and mortality in preterm and small for gestational age infants in the Netherlands enrolled initially 1338 infants born in 1983. The relationship between maximal serum total bilirubin concentration in the neonatal period and neurodevelopmental outcome in the survivors of this cohort was studied. This relationship at the corrected age of 2 years was previously reported. A dose-response relationship between maximal serum total bilirubin concentration and risk of adverse outcome was observed in the 831 surviving children. The present study reassessed the relationship at the age of 5 years in 814 children. There was no significant difference in mean maximal serum total bilirubin concentration between the children with and without a handicap. This was confirmed by logistic regression analysis. After correction for seven suspected confounding factors (gestational age, birth weight, intracranial hemorrhage, ventriculomegaly, seizures, bronchopulmonary dysplasia, and socioeconomic status) the estimated odds ratio was 1.2 (confidence interval 0.89, 1.43) per 50 mumol/L increase of total bilirubin. However, in this analysis an interaction between bilirubin and intracranial hemorrhage was observed. Therefore, the cohort was divided into two groups according to the absence or presence of an intracranial hemorrhage. Logistic regression analysis including four suspected confounding factors (gestational age, ventriculomegaly, seizures, and socioeconomic status) was then again applied. In children who had suffered from an intracranial hemorrhage in the neonatal period the estimated odds ratio was 1.84 (confidence interval 1.08, 3.15) per 50 mumol/L increase of bilirubin. Similar results were obtained treating bilirubin as a categorized exposure. The odds ratio in children without a hemorrhage was 1.05 (confidence interval 0.80, 1.38), probably because of the small number of surviving handicapped children.
R-cadherin expression during nucleus formation in chicken forebrain neuromeres (1995)

The primordial neuroepithelium of the vertebrate forebrain consists of transverse and longitudinal morphogenetic compartments ("neuromeres"). During development, neurons born in the ventricular zone of each neuromere migrate outward to the mantle zone. Here, neuroblasts gradually accumulate and aggregate either into sheets ("laminae") or into roundish structures ("nuclei"). As brain architecture matures, sets of nuclei and laminae derived from several neuromeres become connected by fiber tracts to form functional circuits. We show by immunostaining and in situ hybridization techniques that, in the E3-E5 chicken embryo, the cell adhesion molecule R-cadherin is expressed in several stripes and patches in the forebrain neuroepithelium. This expression pattern reflects, at least in part, the neuromeric organization of the forebrain. For example, in both the ventral and dorsal thalamus, R-cadherin expression has a sharp border at the respective caudal neuromere boundary. Moreover, focusing on the mid-hypothalamic region, we demonstrate that a subset of postmitotic neuroblasts in the ventricular zone express R-cadherin during their migration to the mantle zone, where they aggregate into particular nuclei. In the mantle zone, R-cadherin-expressing neuroblasts accumulate in parallel with neuroblasts expressing another cadherin, N-cadherin. The two types of cells segregate from each other to form adjacent nuclei. Some of the R- and the N-cadherin-positive nuclei form parts of particular functional circuits in the mature brain. In conclusion, our results suggest that cadherins play a role in the formation of brain nuclei and in the developmental transformation from neuromeric to functional organization in the vertebrate forebrain.
Inflammation produces catecholamine resistance in obesity via activation of PDE3B by the protein kinases IKKε and TBK1 (2013)

Obesity produces a chronic inflammatory state involving the NFκB pathway, resulting in persistent elevation of the noncanonical IκB kinases IKKε and TBK1. In this study, we report that these kinases attenuate β-adrenergic signaling in white adipose tissue. Treatment of 3T3-L1 adipocytes with specific inhibitors of these kinases restored β-adrenergic signaling and lipolysis attenuated by TNFα and Poly (I:C). Conversely, overexpression of the kinases reduced induction of Ucp1, lipolysis, cAMP levels, and phosphorylation of hormone sensitive lipase in response to isoproterenol or forskolin. Noncanonical IKKs reduce catecholamine sensitivity by phosphorylating and activating the major adipocyte phosphodiesterase PDE3B. In vivo inhibition of these kinases by treatment of obese mice with the drug amlexanox reversed obesity-induced catecholamine resistance, and restored PKA signaling in response to injection of a β-3 adrenergic agonist. These studies suggest that by reducing production of cAMP in adipocytes, IKKε and TBK1 may contribute to the repression of energy expenditure during obesity. DOI: http://dx.doi.org/10.7554/eLife.01119.001.
Early Metabolic Markers of the Development of Dysglycemia and Type 2 Diabetes and Their Physiological Significance (2012)

Metabolomic screening of fasting plasma from nondiabetic subjects identified α-hydroxybutyrate (α-HB) and linoleoyl-glycerophosphocholine (L-GPC) as joint markers of insulin resistance (IR) and glucose intolerance. To test the predictivity of α-HB and L-GPC for incident dysglycemia, α-HB and L-GPC measurements were obtained in two observational cohorts, comprising 1,261 nondiabetic participants from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) study and 2,580 from the Botnia Prospective Study, with 3-year and 9.5-year follow-up data, respectively. In both cohorts, α-HB was a positive correlate and L-GPC a negative correlate of insulin sensitivity, with α-HB reciprocally related to indices of β-cell function derived from the oral glucose tolerance test (OGTT). In follow-up, α-HB was a positive predictor (adjusted odds ratios 1.25 [95% CI 1.00-1.60] and 1.26 [1.07-1.48], respectively, for each standard deviation of predictor), and L-GPC was a negative predictor (0.64 [0.48-0.85] and 0.67 [0.54-0.84]) of dysglycemia (RISC) or type 2 diabetes (Botnia), independent of familial diabetes, sex, age, BMI, and fasting glucose. Corresponding areas under the receiver operating characteristic curve were 0.791 (RISC) and 0.783 (Botnia), similar in accuracy when substituting α-HB and L-GPC with 2-h OGTT glucose concentrations. When their activity was examined, α-HB inhibited and L-GPC stimulated glucose-induced insulin release in INS-1e cells. α-HB and L-GPC are independent predictors of worsening glucose tolerance, physiologically consistent with a joint signature of IR and β-cell dysfunction.
Increased Levels of Antimicrobial Peptides in Tracheal Aspirates of Newborn Infants during Infection (2002)

Pneumonia and systemic infection are common in premature infants. The antimicrobial peptides human beta-defensin 1 and 2 (hBD-1 and hBD-2) and the cathelicidin LL-37/hCAP-18 are effector molecules of the innate respiratory immune system. It is unknown whether these host defense substances are produced in the respiratory tract of newborns. Concentrations of these peptides were determined in tracheal aspirates of mechanically ventilated newborn infants. All three antimicrobial peptides could be detected in airway lining fluid with equivalent levels in term and preterm newborns. Concentrations of antimicrobial peptides correlated with each other and with levels of interleukin-8 and tumor necrosis factor-alpha in the bronchoalveolar lavage fluid. Pulmonary or systemic infections were associated with significantly increased concentrations of LL-37, hBD-1, and hBD-2. Western blotting detected mature peptides in the lavage fluid. In conclusion, mucosal antimicrobial peptides are present in lung secretions of premature and mature newborns. The molecules are upregulated in response to infection and inflammation and probably represent effector molecules of the respiratory defense system.
Show Me Microsoft Office PowerPoint 2003 (2003)

See it done, do it yourself! Spend less time reading and more time doing with this simple, step-by-step approach to learning the new version of PowerPoint. PowerPoint 2003 provides powerful new tools with which to create presentations more easily, illustrate ideas more powerfully, and share it all in any setting, from meeting rooms to the Web. Based on a proven, successful series format, this book uses a visual page design with easy-to-read text to teach beginning to intermediate level PowerPoint tasks. Troubleshooting guides, see also referencing, sample projects, and MOS objectives add even more for the ambitious learner. Author Steve Johnson is a professional trainer and author of several best-selling books.
Simultaneous prediction of protein secondary structure and transmembrane spans (2013)

Prediction of transmembrane spans and secondary structure from the protein sequence is generally the first step in the structural characterization of (membrane) proteins. Preference of a stretch of amino acids in a protein to form secondary structure and being placed in the membrane are correlated. Nevertheless, current methods predict either secondary structure or individual transmembrane states. We introduce a method that simultaneously predicts the secondary structure and transmembrane spans from the protein sequence. This approach not only eliminates the necessity to create a consensus prediction from possibly contradicting outputs of several predictors but bears the potential to predict conformational switches, i.e., sequence regions that have a high probability to change for example from a coil conformation in solution to an α-helical transmembrane state. An artificial neural network was trained on databases of 177 membrane proteins and 6048 soluble proteins. The output is a 3 × 3 dimensional probability matrix for each residue in the sequence that combines three secondary structure types (helix, strand, coil) and three environment types (membrane core, interface, solution). The prediction accuracies are 70.3% for nine possible states, 73.2% for three-state secondary structure prediction, and 94.8% for three-state transmembrane span prediction. These accuracies are comparable to state-of-the-art predictors of secondary structure (e.g., Psipred) or transmembrane placement (e.g., OCTOPUS). The method is available as web server and for download at www.meilerlab.org.
Carbohydrate and Protein Immobilization onto Solid Surfaces by Sequential Diels−Alder and Azide−Alkyne Cycloadditions (2005)

We demonstrate the applicability of sequential Diels-Alder and azide-alkyne [3 + 2] cycloaddition reactions (click chemistry) for the immobilization of carbohydrates and proteins onto a solid surface. An alpha,omega-poly(ethylene glycol) (PEG) linker carrying alkyne and cyclodiene terminal groups was synthesized and immobilized onto an N-(epsilon-maleimidocaproyl) (EMC)-functionalized glass slide via an aqueous Diels-Alder reaction. In the process, an alkyne-terminated PEGylated surface was provided for the conjugation of azide-containing biomolecules via click chemistry, which proceeded to completion at low temperature and in aqueous solvent. As anticipated, alkyne, azide, cyclodiene, and EMC are independently stable and do not react with common organic reagents nor functional groups in biomolecules. Given an appropriate PEG linker, sequential Diels-Alder and azide-alkyne [3 + 2] cycloaddition reactions provide an effective strategy for the immobilization of a wide range of functionally complex substances onto solid surfaces.
More insight into mesenchymal stem cells and their effects inside the body (2010)

Based on current data, although limited, the mesenchymal-epithelial transition is proposed to be one of the important ways for MSCs to participate tissue repair.
The effects of prolonged phacoemulsification time on the corneal endothelium. (1986)

The question of whether or not phacoemulsification causes significant corneal endothelial damage has been studied in many ways. In this study, we used videotaped specular microscopy and nitroblue tetrazolium (NBT) staining to assess cell damage under conditions in which the two most commonly blamed sources of damage--probe tip trauma and lens fragments--cannot be implicated. After 15 minutes of irrigation, aspiration, and ultrasound in a modified corneal viewing and storage (CVS) chamber, the four test corneas showed less than 5% cell damage as assessed by NBT staining, which was no more than in the control. In one case, an unexpected air bubble on the endothelium caused a loss of endothelial cells. Because small air bubbles are common during phacoemulsification, and because such air bubbles may represent a cause of endothelial cell loss, the endothelial damage caused by air bubbles during phacoemulsification merits further study.
Introducing instant messaging and chat in the workplace (2002)

We report on our experiences of introducing an instant messaging and group chat application into geographically distributed workgroups. We describe a number of issues we encountered, including privacy concerns, individual versus group training, and focusing on teams or individuals. The perception of the tool's utility was a complex issue, depending both on users' views of the importance of informal communication, and their perceptions of the nature of cross-site communication issues. Finally, we conclude with a discussion of critical mass, which is related to the features each user actually uses. More generally, we encountered a dilemma that imposes serious challenges for user-centered design of groupware systems
Cyclotides, a Novel Ultrastable Polypeptide Scaffold for Drug Discovery (2011)

Cyclotides are a unique and growing family of backbone cyclized peptides that also contain a cystine knot motif built from six conserved cysteine residues. This unique circular backbone topology and knotted arrangement of three disulfide bonds makes them exceptionally stable to thermal, chemical, and enzymatic degradation compared to other peptides of similar size. Aside from the conserved residues forming the cystine knot, cyclotides have been shown to have high variability in their sequences. Consisting of over 160 known members, cyclotides have many biological activities, ranging from anti-HIV, antimicrobial, hemolytic, and uterotonic capabilities; additionally, some cyclotides have been shown to have cell penetrating properties. Originally discovered and isolated from plants, cyclotides can also be produced synthetically and recombinantly. The high sequence variability, stability, and cell penetrating properties of cyclotides make them potential scaffolds to be used to graft known active peptides or engineer peptide-based drug design. The present review reports recent findings in the biological diversity and therapeutic potential of natural and engineered cyclotides.