gebhart/patrepeval huggingface dataset:
Glycogen Synthase from Rabbit Skeletal Muscle (1982)

Glycogen synthase has been shown to be phosphorylated in vitro by five protein kinases, cyclic‐AMP‐dependent protein kinase (sites la, 1b and 2). phosphorylase kinase (site 2), glycogen synthase kinase 3 (sites 3a,3b and 3c), glycogen synthase kinase 4 (site 2) and glycogen synthase kinase 5 (site 5) [Cohen,P. et al. (1982) Eur. J. Biochem. 124, 21–35; Picton, C. et al. (1982) Eur. J. Biocliem. 124, 37–45]. All seven serine residues have now been found to be phosphorylated in vivo. Glycogen synthase purified from rabbits that had been injected with l ‐propranolol contained 0.33 mol of phosphate/mol subunit in site la, 0.38 in site Ib, 0.39 in site 2, 1.27 in sites 3a+3b+3c and 0.65 in site 5, totalling 3.0 mol/mol subunit. The activity ratio (∓ glucose‐6 P) for these preparations was 0.21 and their K a for glucose‐6‐P was 1.4mM. Glycogen synthase purified from animals that had been injected with I‐adrenaline contained 0.59 mol phosphate/mol subunit in site la, 0.65 in site lb, 1.03 in site 2, 2.43 in sites 3a + 3b + 3c and 0.65 in site 5, totalling 5.3 mol/mol subunit. The activity ratio of these preparations was 0.04 and their K a for glucose‐6‐P was 6.0mM. The results show that cyclic‐AMP‐dependent protein kinase, glycogen synthase kinase 3 and glycogen synthase kinase 5 act as glycogen synthase kinases in vivo. Glycogen synthase kinase 4 may be largely responsible for the phosphorylation of site 2 in propranolol‐treated animals, and cyclic‐AMP‐dependent protein kinase and phos‐ phorylase kinase for the increased phosphorylation of site 2 in response to adrenaline. The activity of glycogen synthase in vivo in propranolol‐treated animals is largely determined by the state of phosphorylation of sites 3a, 3b and 3c, while the inactivation in response to adrenaline is due to increased phosphorylation at site 2 as well as at sites 3a, 3b and 3c. The finding that the phosphorylation of sites 3a, 3b and 3c is increased from 1.27 mol/mol subunit to 2.43 mol/mol subunit by adrenaline was unexpected, since this enzyme is not regulated by cyclic AMP. Possible explanations for this result are discussed. Phosphofructokinase was isolated as a byproduct of the purification of glycogen synthase. The phosphate content of this enzyme did not differ significantly between l− propranolol‐treated (0.15 mol/mol subunit) and adrenaline‐treated (0.18 mol/mol subunit) animals. These results indicate that muscle phosphofructokinase is not a substrate for cyclic‐AMP‐dependent protein kinase in vivo.
Functional maps of neocortical local circuitry (2007)

This review aims to summarize data obtained with different techniques to provide a functional map of the local circuit connections made by neocortical neurones, a reference for those interested in cortical circuitry and the numerical information required by those wishing to model the circuit. A brief description of the main techniques used to study circuitry is followed by outline descriptions of the major classes of neocortical excitatory and inhibitory neurones and the connections that each layer makes with other cortical and subcortical regions. Maps summarizing the projection patterns of each class of neurone within the local circuit and tables of the properties of these local circuit connections are provided.This review relies primarily on anatomical studies that have identified the classes of neurones and their local and long distance connections and on paired intracellular and whole-cell recordings which have documented the properties of the connections between them. A large number of different types of synaptic connections have been described, but for some there are only a few published examples and for others the details that can only be obtained with paired recordings and dye-filling are lacking. A further complication is provided by the range of species, technical approaches and age groups used in these studies. Wherever possible the range of available data are summarised and compared. To fill some of the more obvious gaps for the less well-documented cases, data obtained with other methods are also summarized.
Development and reliability of a structured interview guide for the Montgomery-Åsberg Depression Rating Scale (SIGMA) (2008)

Use of the SIGMA can result in high reliability of MADRS scores in evaluating patients with depression.
Measurement of tissue oxygen with a fluorescent probe (1976)

Evidence is presented that pyrenebutyric acid is nontoxic at the concentrations required for the measurement of fluorescence quenching by physiological concentrations of oxygen. It appears that this molecule can be used to measure tissue oxygen since it does not interfere with oxygen consumption. Equally, tissue components do not interfere with the quenching of fluorescence to such an extent as to invalidate the method. The spatial resolution of the technique is limited by some tissue geometrical factors which do not, however, appear to be great enough to prevent its use to measure intercapillary oxygen gradients.
Assigning genomic sequences to CATH (2000)

We report the latest release (version 1.6) of the CATH protein domains database (http://www.biochem.ucl. ac.uk/bsm/cath ). This is a hierarchical classification of 18 577 domains into evolutionary families and structural groupings. We have identified 1028 homo-logous superfamilies in which the proteins have both structural, and sequence or functional similarity. These can be further clustered into 672 fold groups and 35 distinct architectures. Recent developments of the database include the generation of 3D templates for recognising structural relatives in each fold group, which has led to significant improvements in the speed and accuracy of updating the database and also means that less manual validation is required. We also report the establishment of the CATH-PFDB (Protein Family Database), which associates 1D sequences with the 3D homologous superfamilies. Sequences showing identifiable homology to entries in CATH have been extracted from GenBank using PSI-BLAST. A CATH-PSIBLAST server has been established, which allows you to scan a new sequence against the database. The CATH Dictionary of Homologous Superfamilies (DHS), which contains validated multiple structural alignments annotated with consensus functional information for evolutionary protein superfamilies, has been updated to include annotations associated with sequence relatives identified in GenBank. The DHS is a powerful tool for considering the variation of functional properties within a given CATH superfamily and in deciding what functional properties may be reliably inherited by a newly identified relative.
Rational design of novel antiandrogens for neutralizing androgen receptor function in hormone refractory prostate cancer (2008)

The results of this study validate our drug discovery rationale based on the structural biology of AR and pave the pay for future development of bifunctional compounds in order to block AR function in hormone refractory stage of prostate cancer.
Local Extravascular Growth Factor Delivery in Myocardial Ischemia (1996)

A number of angiogenic growth factors have been demonstrated in vivo to promote angiogenesis in ischemic myocardium, including basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). We used the porcine ameroid constrictor model to simulate chronic ischemia in an effort to study the role of exogenous growth factor delivery in the development of coronary collateral circulation. Heparin alginate microspheres were used to deliver bFGF, while an implantable osmotic pump was used for VEGF delivery. Anti-von Willebrand antibody staining was used to visualize microvessels in the porcine heart sections obtained from both ischemic and non-ischemic myocardium. A significant increase in the number of microvessels in growth factor-treated pigs compared to control animals was noted. Myocardial blood flow was used to determine the physiologic impact of these findings. In bFGF and VEGF treated animals resting collateral flow values significantly exceeded those of the control group. In addition, both bFGF and VEGF administration resulted in improvements in myocardial perfusion sufficient to prevent stress-induced deterioration of myocardial performance. Results of the studies demonstrate that local perivascular drug delivery can be effectively used to induce angiogenesis in chronically ischemic myocardium.
Hepatic steatosis (2016)

Good level of experimental evidence suggests that citrulline supply may be associated with an attenuation of NAFLD development, but further human studies are now needed to support these findings. This review may help define novel strategies to control fatty liver diseases.
An Integrated Theory of the Mind. (2004)

Adaptive control of thought-rational (ACT-R; J. R. Anderson & C. Lebiere, 1998) has evolved into a theory that consists of multiple modules but also explains how these modules are integrated to produce coherent cognition. The perceptual-motor modules, the goal module, and the declarative memory module are presented as examples of specialized systems in ACT-R. These modules are associated with distinct cortical regions. These modules place chunks in buffers where they can be detected by a production system that responds to patterns of information in the buffers. At any point in time, a single production rule is selected to respond to the current pattern. Subsymbolic processes serve to guide the selection of rules to fire as well as the internal operations of some modules. Much of learning involves tuning of these subsymbolic processes. A number of simple and complex empirical examples are described to illustrate how these modules function singly and in concert.
Improved Detection of Apoptotic Cells in Archival Paraffin Sections: Immunohistochemistry Using Antibodies to Cleaved Caspase 3 (2002)

Apoptosis has gained central importance in the study of many biological processes, including neoplasia, neurodegenerative diseases, and development. One of the limitations of many studies is the difficulty of specifically identifying individual apoptotic cells. Of the many specific methods developed to detect apoptotic cells, most are not applicable to histological sections of archival paraffin-embedded tissues. Recently, advances in the understanding of the molecular events in apoptosis have led to the realization that caspase activation is by far the most specific indicator of this cell suicide mechanism. Several publications have reported the development of antibodies directed at neoepitopes that are generated in various substrates through the action of caspases. One of these is that present on activated caspase 3, a ubiquitously distributed caspase that is a main effector caspase of the apoptotic cascade within cells. This study demonstrates the utility of using a recently commercially available antibody to cleaved caspase 3 in archival paraffin sections, suggesting that this may be a highly specific and sensitive method generally applicable to many studies of archival material.
An HPLC/mass spectrometry platform for the development of multimodality contrast agents and targeted therapeutics: prostate‐specific membrane antigen small molecule derivatives (2006)

The production of disease-targeted agents requires the covalent conjugation of a targeting molecule with a contrast agent or therapeutic, followed by purification of the product to homogeneity. Typical targeting molecules, such as small molecules and peptides, often have high charge-to-mass ratios and/or hydrophobicity. Contrast agents and therapeutics themselves are also diverse, and include lanthanide chelates for MRI, (99m)Tc chelates for SPECT, (90)Y chelates for radiotherapy, (18)F derivatives for PET, and heptamethine indocyanines for near-infrared fluorescent optical imaging. We have constructed a general-purpose HPLC/mass spectrometry platform capable of purifying virtually any targeted agent for any modality. The analytical sub-system is composed of a single dual-head pump that directs mobile phase to either a hot cell for the purification of radioactive agents or to an ES-TOF MS for the purification of nonradioactive agents. Nonradioactive agents are also monitored during purification by ELSD, absorbance and fluorescence. The preparative sub-system is composed of columns and procedures that permit rapid scaling from the analytical system. To demonstrate the platform's utility, we describe the preparation of five small molecule derivatives specific for prostate-specific membrane antigen (PSMA): a gadolinium derivative for MRI, indium, rhenium and technetium derivatives for SPECT, and an yttrium derivative for radiotherapy. All five compounds are derived from a highly anionic targeting ligand engineered to have a single nucleophile for N-hydroxysuccinimide-based conjugation. We also describe optimized column/mobile phase combinations and mass spectrometry settings for each class of agent, and discuss strategies for purifying molecules with extreme charge and/or hydrophobicity. Taken together, our study should expedite the development of disease-targeted, multimodality diagnostic and therapeutic agents.
Comparison of the crystal structures of genetically engineered human manganese superoxide dismutase and manganese superoxide dismutase from thermus thermophilus: Differences in dimer–dimer interaction (1993)

The three-dimensional X-ray structure of a recombinant human mitochondrial manganese superoxide dismutase (MnSOD) (chain length 198 residues) was determined by the method of molecular replacement using the related structure of MnSOD from Thermus thermophilus as a search model. This tetrameric human MnSOD crystallizes in space group P2(1)2(1)2 with a dimer in the asymmetric unit (Wagner, U.G., Werber, M.M., Beck, Y., Hartman, J.R., Frolow, F., & Sussman, J.L., 1989, J. Mol. Biol. 206, 787-788). Refinement of the protein structure (3,148 atoms with Mn and no solvents), with restraints maintaining noncrystallographic symmetry, converged at an R-factor of 0.207 using all data from 8.0 to 3.2 A resolution and group thermal parameters. The monomer-monomer interactions typical of bacterial Fe- and Mn-containing SODs are retained in the human enzyme, but the dimer-dimer interactions that form the tetramer are very different from those found in the structure of MnSOD from T. thermophilus. In human MnSOD one of the dimers is rotated by 84 degrees relative to its equivalent in the thermophile enzyme. As a result the monomers are arranged in an approximately tetrahedral array, the dimer-dimer packing is more intimate than observed in the bacterial MnSOD from T. thermophilus, and the dimers interdigitate. The metal-ligand interactions, determined by refinement and verified by computation of omit maps, are identical to those observed in T. thermophilus MnSOD.
Poly(5-hydroxyoctenylene) and its derivatives: synthesis via metathesis polymerization of an organoborane monomer (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPoly(5-hydroxyoctenylene) and its derivatives: synthesis via metathesis polymerization of an organoborane monomerS. Ramakrishnan and T. C. ChungCite this: Macromolecules 1990, 23, 21, 4519–4524Publication Date (Print):October 1, 1990Publication History Published online1 May 2002Published inissue 1 October 1990https://pubs.acs.org/doi/10.1021/ma00223a004https://doi.org/10.1021/ma00223a004research-articleACS PublicationsRequest reuse permissionsArticle Views285Altmetric-Citations39LEARN 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
Neural differences in the processing of semantic relationships across cultures (2010)

The current study employed functional MRI to investigate the contribution of domain-general (e.g. executive functions) and domain-specific (e.g. semantic knowledge) processes to differences in semantic judgments across cultures. Previous behavioral experiments have identified cross-cultural differences in categorization, with East Asians preferring strategies involving thematic or functional relationships (e.g. cow-grass) and Americans preferring categorical relationships (e.g. cow-chicken). East Asians and American participants underwent functional imaging while alternating between categorical or thematic strategies to sort triads of words, as well as matching words on control trials. Many similarities were observed. However, across both category and relationship trials compared to match (control) trials, East Asians activated a frontal-parietal network implicated in controlled executive processes, whereas Americans engaged regions of the temporal lobes and the cingulate, possibly in response to conflict in the semantic content of information. The results suggest that cultures differ in the strategies employed to resolve conflict between competing semantic judgments.
Global and Local Architecture of the Mammalian microRNA–Transcription Factor Regulatory Network (2007)

microRNAs (miRs) are small RNAs that regulate gene expression at the posttranscriptional level. It is anticipated that, in combination with transcription factors (TFs), they span a regulatory network that controls thousands of mammalian genes. Here we set out to uncover local and global architectural features of the mammalian miR regulatory network. Using evolutionarily conserved potential binding sites of miRs in human targets, and conserved binding sites of TFs in promoters, we uncovered two regulation networks. The first depicts combinatorial interactions between pairs of miRs with many shared targets. The network reveals several levels of hierarchy, whereby a few miRs interact with many other lowly connected miR partners. We revealed hundreds of "target hubs" genes, each potentially subject to massive regulation by dozens of miRs. Interestingly, many of these target hub genes are transcription regulators and they are often related to various developmental processes. The second network consists of miR-TF pairs that coregulate large sets of common targets. We discovered that the network consists of several recurring motifs. Most notably, in a significant fraction of the miR-TF coregulators the TF appears to regulate the miR, or to be regulated by the miR, forming a diversity of feed-forward loops. Together these findings provide new insights on the architecture of the combined transcriptional-post transcriptional regulatory network.
Towards keyword-driven analytical processing (2007)

Gaining business insights from data has recently been the focus of research and product development. On Line-Analytical Processing (OLAP) tools provide elaborate query languages that allow users to group and aggregate data in various ways, and explore interesting trends and patterns in the data. However, the dynamic nature of today's data along with the overwhelming detail at which data is provided, make it nearly impossible to organize the data in a way that a business analyst needs for thinking about the data. In this paper, we introduce "Keyword-Driven Analytical Processing" (KDAP), which combines intuitive keyword-based search with the power of aggregation in OLAP without having to spend considerable effort in organizing the data in terms that the business analyst understands. Our design point is around a user mentality that we frequently encounter: "users don't know how to specify what they want, but they know it when they see it". We present our complete solution framework, which implements various phases from disambiguating the keyword terms to organizing and ranking the results in dynamic facets, that allow the user to explore efficiently the aggregation space. We address specific issues that analysts encounter, like joins, groupings and aggregations, and we provide efficient and scalable solutions. We show, how KDAP can handle both categorical and numerical data equally well and, finally, we demonstrate the generality and applicability of KDAP to two different aspects of OLAP, namely, finding exceptions or surprises in the data and finding bellwether regions where local aggregates are highly correlated with global aggregates, using various experiments on real data.
Inflammatory bowel disease in Asia: A systematic review (2012)

The incidence and prevalence of inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are lower in Asia than in the West. However, across Asia the incidence and prevalence of IBD has increased rapidly over the last two to four decades. These changes may relate to increased contact with the West, westernization of diet, increasing antibiotics use, improved hygiene, vaccinations, or changes in the gut microbiota. Genetic factors also differ between Asians and the Caucasians. In Asia, UC is more prevalent than CD, although CD incidence is rapidly increasing in certain areas. There is a male predominance of CD in Asia, but a trend towards equal sex distribution for UC. IBD is diagnosed at a slightly older age than in the West, and there is rarely a second incidence peak as in the West. A positive family history is much less common than in the West, as are extra-intestinal disease manifestations. There are clear ethnic differences in incidence within countries in Asia, and an increased incidence in IBD in migrants from Asia to the West. Research in Asia, an area of rapidly changing IBD epidemiology, may lead to the discovery of critical etiologic factors that lead to the development of IBD.
Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: Results of a randomized trial (2004)

No effective medical therapy is available for all patients with nonalcoholic steatohepatitis (NASH). Ursodeoxycholic acid (UDCA) has been suggested to be of benefit based on open label clinical studies. We randomized 166 patients with liver biopsy-proven NASH to receive between 13 and 15 mg/kg/d of UDCA or placebo for 2 years. End points included changes in liver test results and liver histology at 2 years of therapy. The treatment groups were comparable at entry with regard to age, gender, risk factors for NASH, serum liver biochemistries, and baseline liver histology. A total of 126 patients completed 2 years of therapy. Pre- and posttreatment liver biopsies were available in 107 patients for review at the end of the study. UDCA was well tolerated and body weight was stable during the study duration. Serum liver biochemistries were stable or improved in both the UDCA and placebo-treated groups. Changes in the degree of steatosis, necroinflammation, or fibrosis that occurred with therapy were not significantly different between the UDCA and placebo groups. In conclusion, 2 years of therapy with UDCA at a dose of 13 to 15 mg/kg/d, although safe and well tolerated, is not better than placebo for patients with NASH.
Trinity of Chillingworth (2007)

Chillingworth is a complicated character in The scarlet letter. His image is a synthesis, or trinity, of the images of God, man of science and Satan, and the novel demonstrates a degradation from God to man of science and finally to a Satan of hatred. In this vicious transformation, his character as man of science plays a key role. Through the development of this character, Hawthorne expresses his criticism to those who lack necessary reverence for human heart and soul.