gebhart/patrepeval huggingface dataset:
Transforming Growth Factor β in Tissue Fibrosis (1994)

Progressive fibrosis in the kidney, liver, lung, heart, bone marrow, and skin is both a major cause of suffering and death and an important contributor to the cost of health care. All of this is likely to change in the future. Advances in cell and cytokine biology have brought a new understanding of the molecular events underlying tissue fibrosis. It is becoming clear that fibrogenesis is not a unique pathologic process but is due to excesses in the same biologic events involved in normal tissue repair1.A central event in tissue repair is the release of cytokines in response . . .
Antiviral Characteristics of GSK1265744, an HIV Integrase Inhibitor Dosed Orally or by Long-Acting Injection (2014)

GSK1265744 is a new HIV integrase strand transfer inhibitor (INSTI) engineered to deliver efficient antiviral activity with a once-daily, low-milligram dose that does not require a pharmacokinetic booster. The in vitro antiviral profile and mechanism of action of GSK1265744 were established through integrase enzyme assays, resistance passage experiments, and cellular assays with site-directed molecular (SDM) HIV clones resistant to other classes of anti-HIV-1 agents and earlier INSTIs. GSK1265744 inhibited HIV replication with low or subnanomolar efficacy and with a selectivity index of at least 22,000 under the same culture conditions. The protein-adjusted half-maximal inhibitory concentration (PA-EC50) extrapolated to 100% human serum was 102 nM. When the virus was passaged in the presence of GSK1265744, highly resistant mutants with more than a 10-fold change (FC) in EC50 relative to that of the wild-type were not observed for up to 112 days of culture. GSK1265744 demonstrated activity against SDM clones containing the raltegravir (RAL)-resistant Y143R, Q148K, N155H, and G140S/Q148H signature variants (FC less than 6.1), while these mutants had a high FC in the EC50 for RAL (11 to >130). Either additive or synergistic effects were observed when GSK1265744 was tested in combination with representative anti-HIV agents, and no antagonistic effects were seen. These findings demonstrate that, similar to dolutegravir, GSK1265744 is differentiated as a new INSTI, having a markedly distinct resistance profile compared with earlier INSTIs, RAL, and elvitegravir (EVG). The collective data set supports further clinical development of GSK1265744.
The Neurobiology of Autism (2007)

Improving clinical tests are allowing us to more precisely classify autism spectrum disorders and diagnose them at earlier ages. This raises the possibility of earlier and potentially more effective therapeutic interventions. To fully capitalize on this opportunity, however, will require better understanding of the neurobiological changes underlying this devastating group of developmental disorders. It is becoming clear that the normal trajectory of neurodevelopment is altered in autism, with aberrations in brain growth, neuronal patterning and cortical connectivity. Changes to the structure and function of synapses and dendrites have also been strongly implicated in the pathology of autism by morphological, genetic and animal modeling studies. Finally, environmental factors are likely to interact with the underlying genetic profile, and foster the clinical heterogeneity seen in autism spectrum disorders. In this review we attempt to link the molecular pathways altered in autism to the neurodevelopmental and clinical changes that characterize the disease. We focus on signaling molecules such as neurotrophin, Reelin, PTEN and hepatocyte growth factor, neurotransmitters such as serotonin and glutamate, and synaptic proteins such as neurexin, SHANK and neuroligin. We also discuss evidence implicating oxidative stress, neuroglial activation and neuroimmunity in autism.
Sequence-Dependent Thermodynamic Parameters for Locked Nucleic Acid (LNA)−DNA Duplex Formation (2004)

The design of modified nucleic acid probes, primers, and therapeutics is improved by considering their thermodynamics. Locked nucleic acid (LNA) is one of the most useful modified backbones, with incorporation of a single LNA providing a substantial increase in duplex stability. In this work, the hybridization DeltaH(o), DeltaS(o), and melting temperature (T(M)) were measured from absorbance melting curves for 100 duplex oligonucleotides with single internal LNA nucleotides on one strand, and the results provided DeltaDeltaH(o), DeltaDeltaS(o), DeltaDelta, and DeltaT(M) relative to reference DNA oligonucleotides. LNA pyrimidines contribute more stability than purines, especially A(L), but there is substantial context dependence for each LNA base. Both the 5' and 3' neighbors must be considered in predicting the effect of an LNA incorporation, with purine neighbors providing more stability. Enthalpy-entropy compensation in DeltaDeltaH(o) and DeltaDeltaS(o) is observed across the set of sequences, suggesting that LNA can stabilize the duplex by either preorganization or improved stacking, but not both simultaneously. Singular value decomposition analysis provides predictive sequence-dependent rules for hybridization of singly LNA-substituted DNA oligonucleotides to their all-DNA complements. The results are provided as sets of DeltaDeltaH(o), DeltaDeltaS(o), and DeltaDelta parameters for all 32 of the possible nearest neighbors for LNA+DNA:DNA hybridization (5' MX(L) and 5' X(L)N, where M, N, and X = A, C, G, or T and X(L) represents LNA). The parameters are applicable within the standard thermodynamic prediction algorithms. They provide T(M) estimates accurate to within 2 degrees C for LNA-containing oligonucleotides, which is significantly better accuracy than previously available.
Tracing the Evolution of the Floral Homeotic B- and C-Function Genes through Genome Synteny (2010)

The evolution of the floral homeotic genes has been characterized using phylogenetic and functional studies. It is possible to enhance these studies by comparing gene content and order between species to determine the evolutionary history of the regulatory genes. Here, we use a synteny-based approach to trace the evolution of the floral B- and C-function genes that are required for specification of the reproductive organs. Consistent with previous phylogenetic studies, we show that the euAP3-TM6 split occurred after the monocots and dicots diverged. The Arabidopsis TM6 and papaya euAP3 genes are absent from the respective genomes, and we have detected loci from which these genes were lost. These data indicate that either the TM6 or the euAP3 lineage genes can be lost without detriment to flower development. In contrast, PI is essential for male reproductive organ development; yet, contrary to predictions, complex genomic rearrangements have resulted in almost complete breakdown of synteny at the PI locus. In addition to showing the evolution of B-function genes through the prediction of ancestral loci, similar reconstructions reveal the origins of the C-function AG and PLE lineages in dicots, and show the shared ancestry with the monocot C-function genes. During our studies, we found that transposable elements (TEs) present in sequenced Antirrhinum genomic clones limited comparative studies. A pilot survey of the Antirrhinum data revealed that gene-rich regions contain an unusually high degree of TEs of very varied types, which will be an important consideration for future genome sequencing efforts.
Intracellular Interleukin-1 Receptor 2 Binding Prevents Cleavage and Activity of Interleukin-1α, Controlling Necrosis-Induced Sterile Inflammation (2013)

Necrosis can induce profound inflammation or be clinically silent. However, the mechanisms underlying such tissue specificity are unknown. Interleukin-1α (IL-1α) is a key danger signal released upon necrosis that exerts effects on both innate and adaptive immunity and is considered to be constitutively active. In contrast, we have shown that necrosis-induced IL-1α activity is tightly controlled in a cell type-specific manner. Most cell types examined expressed a cytosolic IL-1 receptor 2 (IL-1R2) whose binding to pro-IL-1α inhibited its cytokine activity. In cell types exhibiting a silent necrotic phenotype, IL-1R2 remained associated with pro-IL-1α. Cell types possessing inflammatory necrotic phenotypes either lacked IL-1R2 or had activated caspase-1 before necrosis, which degraded and dissociated IL-1R2 from pro-IL-1α. Full IL-1α activity required cleavage by calpain after necrosis, which increased its affinity for IL-1 receptor 1. Thus, we report a cell type-dependent process that fundamentally governs IL-1α activity postnecrosis and the mechanism allowing conditional release of this blockade.
Temperature and stress tuning characteristics of long-period gratings imprinted in Panda fiber (2003)

Temperature and stress tunabilities of long-period Bragg gratings imprinted in Panda fiber are presented in this letter. It is shown that the temperature and strain response of the resonance peaks for fast and slow axes are different not only in their magnitudes but also in the signs of the slope. Furthermore, the characteristics for different order modes are different both in magnitudes and signs. The complicated phenomena are discussed by using a simplified model.
Statistical approach to segmentation of single-channel cerebral MR images (1997)

A statistical model is presented that represents the distributions of major tissue classes in single-channel magnetic resonance (MR) cerebral images. Using the model, cerebral images are segmented into gray matter, white matter, and cerebrospinal fluid (CSF). The model accounts for random noise, magnetic field inhomogeneities, and biological variations of the tissues. Intensity measurements are modeled by a finite Gaussian mixture. Smoothness and piecewise contiguous nature of the tissue regions are modeled by a three-dimensional (3-D) Markov random field (MRF). A segmentation algorithm, based on the statistical model, approximately finds the maximum a posteriori (MAP) estimation of the segmentation and estimates the model parameters from the image data. The proposed scheme for segmentation is based on the iterative conditional modes (ICM) algorithm in which measurement model parameters are estimated using local information at each site, and the prior model parameters are estimated using the segmentation after each cycle of iterations. Application of the algorithm to a sample of clinical MR brain scans, comparisons of the algorithm with other statistical methods, and a validation study with a phantom are presented. The algorithm constitutes a significant step toward a complete data driven unsupervised approach to segmentation of MR images in the presence of the random noise and intensity inhomogeneities.
Catalytic hydrogenation of isoflavones. The preparation of (±)-equol and related isoflavans (1978)

Hydrogenation of daidzein, or preferably its O,O-diacetyl derivative, gives (±)-equol in good yield only over Pd/C prepared according to the Wessely and Prillinger method, whereas other Pd/C catalysts give mixtures of products. Hydrogenation of O,O,O-triacetylgenistein can be used to prepare isoflavan-4',5,7-triol.
STEVIOL GLYCOSIDES AND THEIR USE IN FOOD PROCESSING: A REVIEW (2014)

Steviol glycosides are the proteinacious secondary metabolites present in the leaves of Stevia rebaudiana Bertoni. These SG’s are the principal sweetening agents which are 200-300 times more sweeter than sucrose. A number of SG’s are present in the leaves of Stevia namely, stevioside, dulcoside A, rebaudioside A, rebaudioside B,  rebaudioside C (previously known as dulcoside B),  rebaudioside D, rebaudioside E and steviolbioside, 100–125. At the 63rd meeting a temporary ADI of 0-2 mg/kg bodyweight and day, expressed as steviol, was established based on a No-Observed-Effect-Level (NOEL). Steviol glycoside extracts have broad applications as sweetener in the manufacture of fruit and milk drinks, desserts, yoghurt, delicacies, confectioneries, fruit products, processed seafood products, pickles, table-top  sweeteners and dietary supplements. Other aspects considered are physicochemical and biologic properties for food processing, stability and therapeutic value of SG’s. nutritional information, Stevia market and household uses.
2-Cyanoethyl Phosphate and its Use in the Synthesis of Phosphate Esters1 (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT2-Cyanoethyl Phosphate and its Use in the Synthesis of Phosphate Esters1G. M. TenerCite this: J. Am. Chem. Soc. 1961, 83, 1, 159–168Publication Date (Print):January 1, 1961Publication History Published online1 May 2002Published inissue 1 January 1961https://pubs.acs.org/doi/10.1021/ja01462a032https://doi.org/10.1021/ja01462a032research-articleACS PublicationsRequest reuse permissionsArticle Views1876Altmetric-Citations367LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Gene therapy technologies, applications and regulations : from laboratory to clinic (1999)

Cationic Liposomes for Gene Therapy Applications (J. Clancy & E. Sorscher). DNA Condensation and Receptor-mediated Gene Transfer (A. Ziady & T. Ferkol). Retroviral Vectors (W. Gunzburg & B. Salmons). Lentiviral Vectors (A. Lever). Adenoviral Vectors (S. Connelly). Adeno-associated Viral Vectors (T. Flotte & B. Carter). Advances in Engineering HSV Vectors for Gene Transfer to the Nervous System (M. Soares, et al.). Mammalian Artificial Chromosomes: Prospects for Gene Therapy (T. Ebersole & C. Farr). Gene Therapy for Severe Combined Immunodeficiency (A. Thrasher, et al.). Gene Therapy for Haemophilia (R. Hoeben, et al.). Cystic Fibrosis: Gene Therapy Approaches (N. Caplen). Therapeutic Approaches to Haemoglobinopathies (Y. Beuzard). Gene Therapy Approaches to Duchenne Muscular Dystrophy (S. Murphy & G. Dickson). Lysosomal Storage Diseases (L. Lashford, et al.). Prospects for Gene Therapy of HIV Infections and AIDS (C. Lee, et al.). The Developemnt of the Regulatory Process in Europe for Biological Medicines: How it Affects Gene Therapy Products (A. Meager, et al.). Developement and Regulation of Gene Therapy Drugs in Germany (K. Cichutek). The Transfer of Technology from the Laboratory to the Clinic: In Process Controls and Final Product Testing (F. Borellini & J. Ostrove). Good Laboratory Practice in the Research and Development Laboratory (A. Shepherd). Facilities for Large-scale Production of Vectors Under GMP Conditions (J. Boyd). Addendum. Index.
Demonstration of an ion-implanted, wavelength-shifted quantum-well laser (1996)

A technique for fabricating many different wavelength lasers on the same wafer has been developed. High energy ion implantation was used to selectively blue shift the emission wavelength of an InP-based quantum well laser structure. This structure was then processed into fully functional broad-area lasers whose current threshold was unaffected by the implantation process, indicating extremely high material quality after bandgap-shifting. This process has the potential for the integration of not only different wavelength lasers, but also other devices, such as waveguides, detectors, modulators, etc., on a single wafer.
Selective Staudinger Modification of Proteins Containing p‐Azidophenylalanine (2005)

The unnatural amino acid p-azidophenylalanine was genetically introduced into a phage-displayed peptide and mutant Z-domain protein. These azide-containing proteins were selectively and efficiently modified by using fluorescein-derived phosphines and the Staudinger ligation reaction (see picture). This work provides a powerful new tool for the selective modification of proteins with a variety of synthetic agents. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2268/2005/z500314_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
World Health Organization and International League of Associations for Rheumatology core endpoints for symptom modifying antirheumatic drugs in rheumatoid arthritis clinical trials. (1994)

The WHO/ILAR core set of endpoints for rheumatoid arthritis clinical trials signifies progress in a continuing worldwide effort. This core set includes the following measures: pain, patient global assessment, physical disability, swollen joints, tender joints, acute phase reactants, and physician global assessment; in studies of one or more years' duration, radiographs of joints should be performed.
Metabotropic Glutamate Receptors 1 and 5 Differentially Regulate CA1 Pyramidal Cell Function (2001)

The activation of group I metabotropic glutamate receptors (mGluRs) produces a variety of actions that lead to alterations in excitability and synaptic transmission in the CA1 region of the hippocampus. The group I mGluRs, mGluR1 and mGluR5, are activated selectively by (S)-3,5-dihydroxyphenylglycine (DHPG). To identify which of these mGluR subtypes are responsible for the various actions of DHPG in area CA1, we took advantage of two novel subtype-selective antagonists. (S)-(+)-alpha-amino-a-methylbenzeneacetic acid (LY367385) is a potent competitive antagonist that is selective for mGluR1, whereas 2-methyl-6-(phenylethynyl)-pyridine (MPEP) is a potent noncompetitive antagonist that is selective for mGluR5. The use of these compounds in experiments with whole-cell patch-clamp recording and Ca(2+)-imaging techniques revealed that each group I mGluR subtype plays distinct roles in regulating the function of CA1 pyramidal neurons. The block of mGluR1 by LY367385 suppressed the DHPG-induced increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) and the direct depolarization of CA1 hippocampal neurons. In addition, the increase in the frequency of spontaneous IPSCs (sIPSCs) caused by the DHPG-induced depolarization of inhibitory interneurons also was blocked by LY367385, as was the DHPG-induced inhibition of transmission at the Schaffer collateral-->CA1 synapse. On the other hand, the block of mGluR5 by MPEP antagonized the DHPG-induced suppression of the Ca(2+)-activated potassium current (I(AHP)) and potentiation of the NMDA receptor. Finally, antagonism of the DHPG-induced suppression of evoked IPSCs required the blockade of both mGluR1 and mGluR5. These data suggest that mGluR1 and mGluR5 play distinct roles in the regulation of the excitability of hippocampal CA1 pyramidal neurons.
Direct Comparison of Inhaled Nitric Oxide and Aerosolized Prostacyclin in Acute Respiratory Distress Syndrome (1996)

Inhalation of NO and aerosolization of PGI2 have been suggested to achieve selective pulmonary vasodilation and improvement of arterial oxygenation in patients with ARDS. We directly compared these two modes of transbronchial vasodilator therapy in 16 ARDS patients mechanically ventilated (mean lung injury score [1] 2.75 +/- 0.05). Patients were randomized to receive either first NO and then PGI2, or vice versa. Each drug was individually titrated to find the maximum improvement of arterial oxygenation. Gas exchange variables, including data from the multiple inert gas elimination technique (MIGET), and hemodynamics under application of NO/PGI2 were compared with pre- and post-challenge values. NO (17.8 +/- 2.7 ppm) increased Pa O2/FI O2 from 115 +/- 12 to 144 +/- 15 mm Hg (p<0.01) and reduced the shunt-flow from 33.1 +/- 3.6 to 26.6 +/- 4.5% (p<0.05). Aerosolized PGI2 (7.5 +/- 2.5 ng/kg min) augmented Pa O2/FI O2 from 114 +/- 12 to 135 +/- 12 mm Hg (p<0.01), and decreased shunt from 33.5 +/- 3.8 to 26.0 +/- 3.9% (p<0.05). In 10 patients, both NO and PGI2 caused an increase in Pa O2/FI O2 by at least 10 mm Hg. Two further patients displayed an improvement of arterial oxygenation in response to either NO or PGI2. NO decreased mean pulmonary artery pressure from 34.8 +/- 2.2 to 33.0 +/- 1.8 mm Hg, and PGI2 from 35.0 +/- 2.2 to 31.9 +/- 1.7 mm Hg (p<0.05). We conclude that individually titrated doses of inhaled NO and aerosolized PGI2 effect selective pulmonary vasodilation and redistribute blood-flow from shunt-areas to well-ventilated regions with nearly identical efficacy profiles.
Promoter-regulatory region of the major immediate early gene of human cytomegalovirus. (1984)

The DNA templates containing immediate early (IE) genes of human cytomegalovirus (CMV) were transcribed in vitro by using a HeLa cell extract. When IE region 1, 2, and 3 were used, transcription was detected qualitatively only from IE region 1. Transcription was detected with DNA representing IE region 2 when the IE region 1 promoter was not present. DNA sequence analysis of the upstream regulatory region of IE region 1 detected two distinct repeats of 19 and 18 nucleotides, both being repeated four times. A putative cruciform structure could form through the surrounding sequences with each 18-nucleotide repeat being located in the unpaired region. The potential secondary structure and the repeat sequences in the regulatory region of IE region 1 are presumably related to the high level of transcription of this IE gene.
Bacterial Adhesion: Seen Any Good Biofilms Lately? (2002)

The process of surface adhesion and biofilm development is a survival strategy employed by virtually all bacteria and refined over millions of years. This process is designed to anchor microorganisms in a nutritionally advantageous environment and to permit their escape to greener pastures when essential growth factors have been exhausted. Bacterial attachment to a surface can be divided into several distinct phases, including primary and reversible adhesion, secondary and irreversible adhesion, and biofilm formation. Each of these phases is ultimately controlled by the expression of one or more gene products. Ultrastructurally, the mature bacterial biofilm resembles an underwater coral reef containing pyramidal or mushroom-shaped microcolonies of organisms embedded within an extracellular glycocalyx, with channels and cavities to allow the exchange of nutrients and waste. The biofilm protects its inhabitants from predators, dehydration, biocides, and other environmental extremes while regulating population growth and diversity through primitive cell signals. From a physiological standpoint, surface-bound bacteria behave quite differently from their planktonic counterparts. Recognizing that bacteria naturally occur as surface-bound and often polymicrobic communities, the practice of performing antimicrobial susceptibility tests using pure cultures and in a planktonic growth mode should be questioned. That this model does not reflect conditions found in nature might help explain the difficulties encountered in the management and treatment of biomedical implant infections.