gebhart/patrepeval huggingface dataset:
Teachers researching their teaching: learning through practitioner inquiry (2014)

Teachers researching their teaching: learning through practitioner inquiry
Nature of PO Bonds in Phosphates (2009)

Making use of a combination of ab initio calculated geometries, orbital energies, and orbital spatial distributions as well as experimental information about bond lengths, bond energies, vibrational frequencies, and dipole moments, the nature of the terminal PO bond in phosphates such as (MeO)(3)PO was probed and compared to the case in MeO-P=O where P is trivalent and a PO pi bond is thus assumed to exist. We find that the MeO-P and terminal PO bond lengths in (MeO)(3)PO are essentially the same as in MeO-P=O and the terminal PO lengths are substantially shorter than single P-OMe bond lengths. We also find that the HOMO orbital energies in the two compounds are within 0.1 eV of one another and that these orbitals have spatial characteristics much like one would expect of a bonding pi orbital connecting two atoms from different rows of the periodic table. Using this data, making a comparison to the more familiar bonding arising in N(2), CO, and BF, and taking note of the dipole moments in compounds known to possess dative bonds, we conclude that it is best to represent the terminal PO bond in phosphates in terms of valence-bond structures such as (MeO)(3)P=O in which the formal charges are P(0)O(0) and where a single PO pi bond exists. However, when it comes to characterizing the PO antibonding pi* orbitals, significant differences arise. Electronic structure methods were able to identify the pi* orbital of MeO-P=O and to determine its energy (the MeO-P=O(-) anion is even bound). Similar attempts to identify the PO pi* orbital in the unbound (MeO)(3)P=O(-) anion lead us to conclude that this anion state is probably so strongly coupled to the continuum (i.e., to states corresponding to (MeO)(3)P=O plus a free electron) that it is so short lived as to be undetectable in experiments.
Growth hormone releasing activity by intranasal administration of a synthetic hexapeptide (hexarelin) (1994)

Summary OBJECTIVE Hexarelin is a new synthetic growth hormone releasing peptide. We have tested the efficacy of intranasal (i.n.) administration of hexarelin to stimulate plasma GH and have compared this to the intravenous (i.v.) administration of the peptide. PATIENTS Ten children with familial short stature (FSS) aged 5·5‐15·5 years and two known GH deficient patients aged 24 and 28 years without GH treatment. METHODS All 12 subjects were submitted to i.v. (1 μg/kg) and i.n. (20 μg/kg) hexarelin tests with a one‐week interval between tests. Blood samples for GH, TSH, fT4 and T3 were obtained at 0, 15, 30, 60, 90 and 120 minutes. The hormone determinations were made by standard radio‐immunoassays (RIA). RESULTS Both the i.n. and i.v. administration of hexarelin induced a large GH response, the mean (±SD) being 72·2± 35·5 mU/l for the i.n. test and 79·6 ± 53·0 mU/l for the i.v. test. The peak GH in the i.v. test occurred at 15–30 minutes and in the i.n. test between 30 and 60 minutes. The GH deficient patients showed no GH response In either test. Plasma TSH decreased in the FSS children from a mean (±SD) of 1.0 ± 0·26 to 0·64±0 2 mU/l ( P <0 005) during the i.n. test and from 1·0±0·3 to 0·7±0·3mU/l ( P > 0 05) during the I.v. test. In the isolated GH deficient patient, plasma TSH decreased from 1·06±0·38 mU/l to 0·86±0·17 during the i.v. test and from 1·60±0·01 to 1·11±0·06mU/l during the i.n. test. There were no significant changes in plasma fT4 or T3 in any of the tests. CONCLUSIONS The synthetic hexapeptide hexarelin is a potent pituitary GH stimulator when administered intra‐nasally. The GH response was similar to that observed after intravenous hexarelin. Simultaneously, there was a significant decrease in plasma TSH but the concentrations remained in the normal range. These findings appear to be of theoretical and practical relevance to the investigation and management of short children.
Polyphenol (-)-Epigallocatechin Gallate during Ischemia Limits Infarct Size Via Mitochondrial K<sub>ATP</sub>Channel Activation in Isolated Rat Hearts (2010)

Polyphenol (-)-epigallocatechin gallate (EGCG), the most abundant catechin of green tea, appears to attenuate myocardial ischemia/reperfusion injury. We investigated the involvement of ATP-sensitive potassium (K(ATP)) channels in EGCG-induced cardioprotection. Isolated rat hearts were subjected to 30 min of regional ischemia and 2 hr of reperfusion. EGCG was perfused for 40 min, from 10 min before to the end of index ischemia. A nonselective K(ATP) channel blocker glibenclamide (GLI) and a selective mitochondrial K(ATP) (mK(ATP)) channel blocker 5-hydroxydecanoate (HD) were perfused in EGCG-treated hearts. There were no differences in coronary flow and cardiodynamics including heart rate, left ventricular developed pressure, rate-pressure product, +dP/dt(max), and -dP/dt(min) throughout the experiments among groups. EGCG-treatment significantly reduced myocardial infarction (14.5+/-2.5% in EGCG 1 microM and 4.0+/-1.7% in EGCG 10 microM, P<0.001 vs. control 27.2+/-1.4%). This anti-infarct effect was totally abrogated by 10 microM GLI (24.6+/-1.5%, P<0.001 vs. EGCG). Similarly, 100 microM HD also aborted the anti-infarct effect of EGCG (24.1+/-1.2%, P<0.001 vs. EGCG ). These data support a role for the K(ATP) channels in EGCG-induced cardioprotection. The mK(ATP) channels play a crucial role in the cardioprotection by EGCG.
Effect of cilostazol on cerebral blood flows in chronic stage of cerebral circulation. (2000)

In order to find out the difference between cilostazol and ticlopidine hydrochloride in the cerebral vasodilating effect in the chronic stage of cerebral infarction, cerebral blood flows were measured while the patients were on ticlopidine hydrochloride and after ticlopidine hydrochloride was switched to cilostazol. Single photon emission computed tomography (SPECT) was performed using Prism 2000XP gamma camera system. Ultrasound examinations of the carotid artery was performed using Ultramark 9. The blood flows in the frontal white matter, temporal cortex and occipital cortex after cilostazol were significantly higher than those before cilostazol. The peak systolic velocity, time-averaged peak velocity and volume flow after cilostazol were significantly higher than those before cilostazol. The total cholesterol, triglyceride and apolipoprotein B concentrations after cilostazol were significantly lower than those before cilostazol. The present study suggests that cilostazol has better influence on cerebral circulation than ticlopidine hydrochloride in the chronic stage of cerebral infarction.
Population Dynamics of Phenol-Degrading Bacteria in Activated Sludge Determined by <i>gyrB</i> -Targeted Quantitative PCR (1998)

A method for quantifying bacterial populations introduced into an activated-sludge microbial community is described. The method involves extraction of DNA from activated sludge, appropriate dilution of the extracted DNA with DNA extracted from nonintroduced activated sludge, PCR amplification of a gyrB gene fragment from the introduced strain with a set of strain-specific primers, and quantification of the electrophoresed PCR product by densitometry. The adequacy of the method was examined by analyzing the population dynamics of two phenol-degrading bacteria, Pseudomonas putida BH and Comamonas sp. strain E6, that had been introduced into phenol-digesting activated sludge. The density of each of the two populations determined by the PCR method immediately after the introduction was consistent with the density estimated from a plate count of the inoculum. This quantitative PCR method revealed different population dynamics for the two strains in the activated sludge under different phenol-loading conditions. The behavior of both of these strains in the activated sludge reflected the growth kinetics of the strains determined in laboratory axenic cultures.
Phase II Study of Bevacizumab and Vorinostat for Patients with Recurrent World Health Organization Grade 4 Malignant Glioma (2017)

Combination treatment of BEV and VOR was well tolerated. This combination therapy for this study population did not improve PFS6 or median OS when compared with BEV monotherapy.
Profiling and Characterizing Skin Ceramides Using Reversed-Phase Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry (2011)

An LC-MS based method for the profiling and characterization of ceramide species in the upper layer of human skin is described. Ceramide samples, collected by tape stripping of human skin, were analyzed by reversed-phase liquid chromatography coupled to high-resolution quadrupole time-of-flight mass spectrometry operated in both positive and negative electrospray ionization mode. All known classes of ceramides could be measured in a repeatable manner. Furthermore, the data set showed several undiscovered ceramides, including a class with four hydroxyl functionalities in its sphingoid base. High-resolution MS/MS fragmentation spectra revealed that each identified ceramide species is composed of several skeletal isomers due to variation in carbon length of the respective sphingoid bases and fatty acyl building blocks. The resulting variety in skeletal isomers has not been previously demonstrated. It is estimated that over 1000 unique ceramide structures could be elucidated in human stratum corneum. Ceramide species with an even and odd number of carbon atoms in both chains were detected in all ceramide classes. Acid hydrolysis of the ceramides, followed by LC-MS analysis of the end-products, confirmed the observed distribution of both sphingoid bases and fatty acyl groups in skin ceramides. The study resulted in an accurate mass retention time library for targeted profiling of skin ceramides. It is furthermore demonstrated that targeted data processing results in an improved repeatability versus untargeted data processing (72.92% versus 62.12% of species display an RSD < 15%).
Introduction to Smoothing (1999)

The prelims comprise: Slicing a Scatterplot Estimating E(y|x) by Slicing Checking a Theory Boxplots Snow Geese Complements Problems
Vertex Entropy As a Critical Node Measure in Network Monitoring (2017)

Understanding which node failures in a network have more impact is an important problem. Current understanding, motivated by the scale free models of network growth, places emphasis on the degree of the node. This is not a satisfactory measure; the number of connections a node has does not capture how redundantly it is connected into the whole network. Conversely, the structural entropy of a graph captures the resilience of a network well, but is expensive to compute, and, being a global measure, does not attribute any specific value to a given node. This lack of locality prevents the use of global measures as a way of identifying critical nodes. In this paper, we introduce local vertex measures of entropy which do not suffer from such drawbacks. In our theoretical analysis, we establish the possibility that our local vertex measures approximate global entropy, with the advantage of locality and ease of computation. We establish properties that vertex entropy must have in order to be useful for identifying critical nodes. We have access to a proprietary event, topology, and incident dataset from a large commercial network. Using this dataset, we demonstrate a strong correlation between vertex entropy and incident generation over events.
Chemogenomic Profiling of Human and Microbial FK506-Binding Proteins (2018)

FK506-binding proteins (FKBPs) are evolutionarily conserved proteins that display peptidyl-prolyl isomerase activities and act as coreceptors for immunosuppressants. Microbial macrophage-infectivity-potentiator (Mip)-type FKBPs can enhance infectivity. However, developing druglike ligands for FKBPs or Mips has proven difficult, and many FKBPs and Mips still lack biologically useful ligands. To explore the scope and potential of C<sup>5</sup>-substituted [4.3.1]-aza-bicyclic sulfonamides as a broadly applicable class of FKBP inhibitors, we developed a new synthesis method for the bicyclic core scaffold and used it to prepare an FKBP- and Mip-focused library. This allowed us to perform a systematic structure-activity-relationship analysis across key human FKBPs and microbial Mips, yielding highly improved inhibitors for all the FKBPs studied. A cocrystal structure confirmed the molecular-binding mode of the core structure and explained the affinity gained as a result of the preferred substituents. The best FKBP and Mip ligands showed promising antimalarial, antileginonellal, and antichlamydial properties in cellular models of infectivity, suggesting that substituted [4.3.1]-aza-bicyclic sulfonamides could be a novel class of anti-infectives.
Extraction of alkaloids and oil from bitter lupin seed (1982)

Abstract Quinolizidine alkaloids and the oil were recovered from seeds of bitter lupin, Lupinus mutabilis , by 2 extractions using hexane as the only organic solvent, Ground and flaked lupin seed was extracted first with hexane, which recovers the oil and those alkaloids that occur as free bases. Subsequently, the hexane‐insoluble salts of the alkaloids retained in the defatted flakes were converted into hexanesoluble free bases by treatment with aq sodium carbonate or ammonium hydroxide and removed by another extraction with hexane. A low‐alkaloid proteinaceous meal was obtained with practically no loss of protein. The alkaloids dissolved in the oil were completely recovered by extraction with aq hydrochloric acid.
Stereoselective Synthesis of Highly Substituted .gamma.-Lactones and Butenolides by Intramolecular Michael Addition of Enantiomerically Enriched .gamma.-[(Phenylthio)acyl]oxy .alpha.,.beta.-Unsaturated Esters (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereoselective Synthesis of Highly Substituted .gamma.-Lactones and Butenolides by Intramolecular Michael Addition of Enantiomerically Enriched .gamma.-[(Phenylthio)acyl]oxy .alpha.,.beta.-Unsaturated EstersCarmen M. Rodriguez, Tomas Martin, Miguel A. Ramirez, and Victor S. MartinCite this: J. Org. Chem. 1994, 59, 16, 4461–4472Publication Date (Print):August 1, 1994Publication History Published online1 May 2002Published inissue 1 August 1994https://pubs.acs.org/doi/10.1021/jo00095a022https://doi.org/10.1021/jo00095a022research-articleACS PublicationsRequest reuse permissionsArticle Views456Altmetric-Citations29LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Periodic courses of human 1–34 parathyroid peptide alternating with calcitriol paradoxically reduce bone remodelling in spinal osteoporosis (1987)

Abstract. In an attempt to achieve an anabolic response in both axial and peripheral bone, we treated twelve patients with osteoporosis using human 1–34 parathyroid peptide given discontinuously. The peptide was given as seven daily subcutaneous injections followed by 21 days' treatment with 0·25 mg calcitriol orally. This regime was repeated cyclically for at least sixteen cycles, of which the first four were at a lower dose of hPTH 1–34 than used subsequently. The results of treatment were monitored by kinetic, densitometric, histomorphometric and biochemical studies performed before and during treatment. Two patients developed hPTH 1–34 binding in their plasma during treatment: this was presumed to be due to the development of antibodies. The remainder, instead of increasing their indices of bone turnover as judged by iliac bone histomorphometry, were found to have consistent reductions in trabecular resorption surfaces. The other indices of bone formation and resorption measured showed no change or comparable reductions. The small increases seen in total body calcium were consistent with ‘in‐filling’ of deleted basic multicellular units (BMUs). Because there is no evidence that calcitriol alone causes comparable reductions in activation of bone remodelling in osteoporosis, interruption of treatment with hPTH 1–34 after 7 days may have led to a failure of the activation mechanism to proceed to the resorption stage, with a consequent overall reduction in remodelling activity. This type of treatment regime, with its calcitonin‐like effect, might be effective in reducing net bone loss due to imbalance between bone formation and resorption at the BMU level, particularly in patients with increased numbers of BMUs (‘high turnover’ osteoporosis). However, it proved a less promising regime than daily injections of PTH 1–34 or sodium fluoride plus calcium therapy for the substantial reversal of axial trabecular bone loss in patients able to respond to these therapies.
Disruptive Effect of Chloroquine on Lysosomes in Cultured Rat Hepatocytes (2005)

Chloroquine has been used as an anti-malarial drug and is known as a lysosomotropic amine as well. The effects of chloroquine on lysosomal integrity in cultured rat hepatocytes were studied by measuring lysosomal enzyme beta-glucuronidase (beta-G) or lysosomal membrane glycoprotein (lamp-1) in Percoll density gradient fractions, in the cytosolic fraction obtained from cells permeabilized by digitonin or in the cytosolic fraction obtained by conventional cell fractionation. The distribution of beta-G on a Percoll density gradient in chloroquine-treated cells was approximately similar to that of a cytosolic protein, mevalonate pyrophosphate decarboxylase, in nontreated cells. Lamp-1 was decreased in the lysosomal fractions on a Percoll density gradient in chloroquine-treated cells, and was increased in the plasma membrane fraction, as compared with the levels in nontreated cells. Furthermore, after cells were cultured in the presence and absence of chloroquine, the proportions of beta-G activity in the cytosolic fraction obtained from the digitonin-permeabilized cells were 19% and 4%, while those in the cytosolic fraction obtained by conventional cell fractionation were 54% and 26%, respectively. From these findings, we infer that chloroquine caused the disruption of lysosomes in the living cells, and that lysosomes treated with chloroquine were easily disrupted by homogenization or centrifugation during cell fractionation.
Heat shock protein hsp70 accelerates the recovery of heat-shocked mammalian cells through its modulation of heat shock transcription factor HSF1. (1995)

The role of mammalian 70-kDa heat shock protein (hsp70) in regulating cellular response to heat shock was examined by using three closely related rat cells: control Rat-1 cells, thermotolerant Rat-1 (TT Rat-1) cells, and heat-resistant M21 cells, a derivative of Rat-1 cells that constitutively overexpress human hsp70. In all these cells, after a prescribed heat shock, the level of the phosphorylated form of heat shock transcription factor HSF1 and that of HSF1 capable of binding to its cognitive DNA sequence heat shock element (HSE) exhibit similar time dependence. The amount of a constitutive HSE-binding activity (CHBA), on the other hand, inversely correlates with those of the two aforementioned forms of HSF1. The recovery kinetics from heat shock are different for the three cell lines, with the thermal-resistant TT Rat-1 and M21 cells showing faster recovery in terms of the state of phosphorylation of HSF1 and its ability to bind HSE or in terms of the reappearance of CHBA. Treatment with okadaic acid, a serine/threonine phosphatase inhibitor, delays the recovery kinetics of Rat-1 cells but not that of thermal-resistant M21 cells. These results are interpreted in terms of a role for hsp70 in the recovery of heat-shocked mammalian cells.
Conversion of encapsulated 5-fluoro-2'-deoxyuridine 5'-monophosphate to the antineoplastic drug 5-fluoro-2'-deoxyuridine in human erythrocytes. (1988)

The fluoropyrimidine deoxyribonucleotide 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) was encapsulated in human erythrocytes by a procedure based on hypotonic hemolysis and isotonic resealing. Encapsulated FdUMP (up to 9 mumol/ml of packed erythrocytes) did not affect erythrocyte metabolism or morphology. Hemolysates were found to catalyze efficient dephosphorylation of FdUMP to yield nearly stoichiometric amounts of the corresponding deoxyribonucleoside 5-fluoro-2'-deoxyuridine (FdUrd), an antineoplastic drug showing selective cytotoxicity toward liver metastases from colorectal carcinomas. The dephosphorylation reaction had an apparent Km of 7.7 +/- 1.2 mM FdUMP at pH 7.4 and was remarkably slower at pH 8.2. ATP, GTP, and UTP inhibited both the disappearance of FdUMP and the formation of FdUrd in hemolysates. The enzyme responsible for the FdUMP-to-FdUrd conversion was identified with the deoxyribonucleotide-specific isozyme of erythrocyte pyrimidine 5'-nucleotidase (EC 3.1.3.5). Intracellular formation and subsequent release of FdUrd were observed in intact erythrocytes loaded with FdUMP. Inhibition of FdUrd release from these erythrocytes was obtained by raising the pH intracellularly and, alternatively, by coencapsulation of ATP. Autologous FdUMP-loaded erythrocytes might be used as endogenous bioreactors designed for time-programmed and liver-targeted delivery of FdUrd.
Tissue-specific expression of the gene encoding hepatocyte nuclear factor 1 may involve hepatocyte nuclear factor 4. (1991)

Hepatocyte nuclear factor 1 (HNF-1) is a transcriptional regulatory protein possibly involved in the activation of many liver-specifically expressed genes. HNF-1 mRNA is restricted to a small number of tissues, suggesting that the HNF-1 gene itself is regulated at the transcriptional level. We have isolated and characterized the promoter region of this gene and have determined its transcriptional potential in several cell types by cell-free transcription and transient transfection experiments. In in vitro transcription assays, an HNF-1 promoter is active in nuclear extracts from liver and kidney, two tissues that contain HNF-1, but silent in nuclear extracts from spleen and lung, which are devoid of this transcription factor. Likewise, in transfection experiments, HNF-1 promoter-chloramphenicol acetyltransferase (CAT) fusion genes are expressed in Hep G2 cells, which express HNF-1, but not in mouse L cells or Hela cells, which do not express HNF-1. In both cell-free transcription and transient transfection assays, a relatively short promoter segment located between positions -82 and -40 is necessary and sufficient to direct cell type-specific HNF-1 transcription. This region contains a single site for a DNA-binding protein that has been tentatively identified as hepatocyte nuclear factor 4, a member of the steroid hormone receptor family.