gebhart/patrepeval huggingface dataset:
N‐Substituted Phenothiazine Derivatives: How the Stability of the Neutral and Radical Cation Forms Affects Overcharge Performance in Lithium‐Ion Batteries (2014)

Phenothiazine and five N-substituted derivatives were evaluated as electrolyte additives for overcharge protection in LiFePO4 /synthetic graphite lithium-ion batteries. We report on the stability and reactivity of both the neutral and radical-cation forms of these six compounds. While three of the compounds show extensive overcharge protection, the remaining three last for only one to a few cycles. UV/Vis studies of redox shuttle stability in the radical cation form are consistent with the overcharge performance: redox shuttles with spectra that show little change over time exhibit extensive overcharge performance, whereas those with changing spectra have limited overcharge protection. In one case, we determined that a C-N bond cleaves upon oxidation, forming the phenothiazine radical cation and leading to premature overcharge protection failure; in another case, poor solubility appears to limit protection.
Structural and functional analysis of temperature-sensitive mutants of the phage phi 29 DNA polymerase. (1990)

The cloning and complete sequencing of gene 2 from four independently isolated temperature-sensitive mutants in the phage phi 29 DNA polymerase (ts2 mutants) is reported. The results obtained indicate that, in vivo, the mutations only affect the initial steps of the replication process. Interestingly, three of these mutations consist in the single amino acid change Ala to Val at position 492 of the protein. The ts2(24) and ts2(98) mutant phi 29 DNA polymerases were expressed, purified and their thermosensitivity was studied at two different steps of DNA replication: 1) protein-primed initiation and 2) elongation of the DNA chain. Whereas the ts2(24) mutation gave rise to a temperature-sensitive phenotype in both reactions, the ts2(98) mutant protein was rather insensitive to the temperature increase. In addition, the ts2(98) mutant protein showed clear differences in the activation by divalent cations. The relationship of these results with structural and functional domains in the phi 29 DNA polymerase are discussed.
Recent progress in three-dimensional information processing based on integral imaging (2009)

Recently developed integral imaging techniques are reviewed. Integral imaging captures and reproduces the light rays from the object space, enabling the acquisition and the display of the three-dimensional information of the object in an efficient way. Continuous effort on integral imaging has been improving the performance of the capture and display process in various aspects, including distortion, resolution, viewing angle, and depth range. Digital data processing of the captured light rays can now visualize the three-dimensional structure of the object with a high degree of freedom and enhanced quality. This recent progress is of high interest for both industrial applications and academic research.
GROWTH INHIBITION OF CLOSTRIDIUM FESERI BY CARCINOSTATIC PURINE AND PYRIMIDINE ANALOGS. I. EFFECT OF MEDIUM ON GROWTH INHIBITION. (1964)

Summary Clostridium feseri (chuavoei), ATCC-10092, grows well in a semi-synthetic basal medium devoid of purine bases and folic acid. Growth inhibition of this organism in such a medium by carcinostatic purine analogs is pronounced, and by pyrimidine analogs marked. Purines in the medium block the growth inhibition of Clostridium feseri by purine analogs. Greater agreement occurs between the growth inhibition of the organism and Adenocarcinoma 755 when carcinostatic purine and pyrimidine analogs are studied in purineless media as compared with complex thioglycollate medium.
Design, Synthesis, and Biochemical Evaluation of Phosphonate and Phosphonamidate Analogs of Glutathionylspermidine as Inhibitors of Glutathionylspermidine Synthetase/Amidase fromEscherichia coli (1997)

Three phosphapeptides designed to mimic two distinct tetrahedral intermediates formed during either the synthesis or hydrolysis of glutathionylspermidine (Gsp) were synthesized and evaluated as inhibitors of the bifunctional enzyme Gsp synthetase/amidase. While the polyamine-containing phosphapeptides were determined to be potent and selective inhibitors, they selectively inhibit the synthetase activity over the amidase domain. A phosphonate-containing tetrahedral mimic is a reversible mixed-type inhibitor of Gsp synthetase with an inhibition constant of 6 microM for the inhibitor binding to the free enzyme (Ki) and 14 microM for the inhibitor binding to the enzyme-substrate complex (Ki'). The corresponding phosphonamidate is a slow-binding inhibitor with a Ki of 24 microM and a Ki* (isomerization inhibition constant) of 0.88 microM. A non-polyamine-containing phosphonamidate exhibits no significant inhibition of the synthetase or amidase activity.
Effect of microencapsulated ampicillin on cell-mediated immune responses in mice (1997)

The effects of free ampicillin, microencapsulated ampicillin anhydrate (MEAA) and antibiotic-free microspheres on the cell-mediated immune response in Balb/c mice were measured by lymphoproliferation assay, delayed-type hypersensitivity (DTH) and cytokine production. Injection into mice for seven consecutive days with equivalent subcutaneous doses of ampicillin, MEAA or placebo microspheres did not produce any consistent change in lymphocyte proliferation nor did it affect DTH responses or interleukin-2 production. Although the production of interleukin-4 in mice treated with ampicillin or MEAA increased compared with the control mice, this increase was not statistically significant. These results indicate that ampicillin and MEAA have similar effects on cell-mediated immunity in mice.
Androgen receptor inactivation contributes to antitumor efficacy of 17α-hydroxylase/17,20-lyase inhibitor 3β-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene in prostate cancer (2008)

We previously reported that our novel compound 3beta-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene (VN/124-1) is a potent 17alpha-hydroxylase/17,20-lyase (CYP17) inhibitor/antiandrogen and strongly inhibits the formation and proliferation of human prostate cancer LAPC4 tumor xenografts in severe combined immunodeficient mice. In this study, we report that VN/124-1 and other novel CYP17 inhibitors also cause down-regulation of androgen receptor (AR) protein expression in vitro and in vivo. This mechanism of action seems to contribute to their antitumor efficacy. We compared the in vivo antitumor efficacy of VN/124-1 with that of castration and a clinically used antiandrogen, Casodex, and show that VN/124-1 is more potent than castration in the LAPC4 xenograft model. Treatment with VN/124-1 (0.13 mmol/kg twice daily) was also very effective in preventing the formation of LAPC4 tumors (6.94 versus 2410.28 mm(3) in control group). VN/124-1 (0.13 mmol/kg twice daily) and VN/124-1 (0.13 mmol/kg twice daily) + castration induced regression of LAPC4 tumor xenografts by 26.55% and 60.67%, respectively. Treatments with Casodex (0.13 mmol/kg twice daily) or castration caused significant tumor suppression compared with control. Furthermore, treatment with VN/124-1 caused marked down-regulation of AR protein expression, in contrast to treatments with Casodex or castration that caused significant up-regulation of AR protein expression. The results suggest that VN/124-1 acts by several mechanisms (CYP17 inhibition, competitive inhibition, and down-regulation of the AR). These actions contribute to inhibition of the formation of LAPC4 tumors and cause regression of growth of established tumors. VN/124-1 is more efficacious than castration in the LAPC4 xenograft model, suggesting that the compound has potential for the treatment of prostate cancer.
Targeted brain delivery of itraconazole via RVG29 anchored nanoparticles (2010)

The blood-brain barrier is a major barrier in the neurological diseases treatment and precludes the entry of drugs from blood to brain. Here, we developed 29-amino-acid peptide derived from rabies virus glycoprotein (RVG29) peptide conjugated itraconazole-loaded albumin nanoparticles (RVG29-ITZ-NPs). The RVG29 peptide was conjugated to the albumin NPs using biotin-binding streptavidin as crosslinker. The NPs were characterized in terms of particle size, zeta potential, drug loading and release behavior in vitro. Cellular uptake of RVG29-ITZ-NPs was investigated by flow cytometry. Pharmacokinetics and brain distribution of RVG29-ITZ-NPs were investigated after intravenous administration of NPs. The particle size of RVG29-ITZ-NPs was 89.3 ± 1.9 nm as determined by dynamic light scattering. The zeta potential of RVG29-ITZ-NPs was -33.1 ± 0.9 mV. RVG29-ITZ-NPs exhibited a sustained release profile within 24 h. In vitro cellular uptake studies demonstrated that RVG29 significantly facilitated the intracellular delivery of NPs. A significant (P < 0.05) accumulation of ITZ in brain was observed for RVG29-ITZ-NPs as compared with ITZ-NPs and cyclodextrin formulation of ITZ (ITZ-CD). These results suggested that RVG29-ITZ-NPs can be exploited as a potential therapeutic formulation for the intracranial fungal infection.
The Genetics of Lignin Biosynthesis: Connecting Genotype to Phenotype (2010)

The processes underlying lignification, which for many years have been the near-exclusive purview of chemists and biochemists, have more recently been approached using both classical forward genetic screens and targeted reverse genetic approaches such as antisense suppression, RNAi, and characterization of insertional mutants. In this review, we provide an overview of the current understanding of lignin biosynthesis and structure, with emphasis on mutant and transgenic plants that have contributed to this knowledge. We also discuss ongoing work aimed at elucidating the relationship between lignin structure and function in vivo, as well as the phenotypic consequences arising from genetic manipulation of the lignin biosynthetic pathway.
A new inverse kinematics algorithm for binary manipulators with many actuators (2001)

In this paper we present a new, and extremely fast, algorithm for the inverse kinematics of discretely actuated manipulator arms with many degrees of freedom. Our only assumption is that the arm is macroscopically serial in structure, meaning that the overall structure is a serial cascade of units with each unit having either a serial or parallel kinematic structure. Our algorithm builds on previous works in which the authors and coworkers have used the workspace density function in a breadthfirst search for solving the inverse kinematics problem. The novelty of the method presented here is that only the 'mean' of this workspace density function is used. Hence the requirement of storing a sampled version of the workspace density function (which is a function on a six-dimensional space in the case of a spatial manipulator) is circumvented. We illustrate the technique with both planar revolute and variable-geometry-truss manipulators, and briefly describe a new manipulator design for which this algorithm is applicable.
Anti‐HCV therapies in chimeric scid‐Alb/uPA mice parallel outcomes in human clinical application† (2006)

Compounds with in vitro anti-hepatitis C virus (HCV) activity are often advanced directly into clinical trials with limited or no in vivo efficacy data. This limits prediction of clinical efficacy of compounds in the HCV drug pipeline, and may expose human subjects to unnecessary treatment effects. The scid-Alb-uPA mouse supports proliferation of transplanted human hepatocytes and subsequent HCV infection. Cohorts of genotype 1a HCV-infected mice were treated with interferon alpha-2b(IFN-alpha), BILN-2061 (anti-NS3 protease), or HCV371 (anti-NS5B polymerase). Mice treated with 1350 IU/g/day IFN-alpha intramuscularly for 10 to 28 days demonstrated reduced viral titers compared with controls in all five experiments (P < .05, t test); viral titers rebounded after treatment withdrawal. A more pronounced antiviral effect with IFN-alpha was seen in genotype 3a-infected mice. Pilot studies with BILN2061 confirmed exposure to 10X replicon EC50 at trough and reduced viral titer over 2 log at 4 days. In a second 7-day study, mean HCV RNA titers dropped 1.1 log in BILN2061-treated animals, 0.6 log in IFN-treated mice, and rose 0.2 log in controls (P = .013, ANOVA). Pre-existing mutants with partial resistance to BILN2061 were identified by sequencing both the human inoculum and sera from treated mice. The polymerase inhibitor HCV371 yielded a decline in HCV titers of 0.3 log relative to vehicle-treated controls (P = NS). Performance of all three antiviral regimens in the chimeric mouse model paralleled responses in humans. In conclusion, this system may help selection of lead compounds for advancement into human trials with an increased likelihood of clinical success while broadening the tools available for study of the biology of HCV infection.
Classification of signatures of Bovine Spongiform Encephalopathy in serum using infrared spectroscopy (2004)

Signatures of Bovine Spongiform Encephalopathy (BSE) have been identified in serum by means of "Diagnostic Pattern Recognition (DPR)". For DPR-analysis, mid-infrared spectroscopy of dried films of 641 serum samples was performed using disposable silicon sample carriers and a semi-automated DPR research system operating at room temperature. The combination of four mathematical classification approaches (principal component analysis plus linear discriminant analysis, robust linear discriminant analysis, artificial neural network, support vector machine) allowed for a reliable assignment of spectra to the class "BSE-positive" or "BSE-negative". An independent, blinded validation study was carried out on a second DPR research system at the Veterinary Laboratory Agency, Weybridge, UK. Out of 84 serum samples originating from terminally-ill, BSE-positive cattle, 78 were classified correctly. Similarly, 73 out of 76 BSE-negative samples were correctly identified by DPR such that, numerically, an accuracy of 94.4 % can be calculated. At a confidence level of 0.95 (alpha = 0.05) these results correspond to a sensitivity > 85% and a specificity > 90%. Identical class assignment by all four classifiers occurred in 75% of the cases while ambiguous results were obtained in only 8 of the 160 cases. With an area under the ROC (receiver operating charateristics) curve of 0.991, DPR may potentially supply a valuable surrogate marker for BSE even in cases in which a deliberate bias towards improved sensitivity or specificity is desired. To the best of our knowledge, DPR is the first and--up to now--only method which has demonstrated its capability of detecting BSE-related signatures in serum.
Characterization of the receptor for glucagon-like peptide-1(7–36)amide on plasma membranes from rat insulinoma-derived cells by covalent cross-linking (1989)

125I-Labelled glucagon-like peptide-1(7-36)amide was cross-linked to a specific binding protein in plasma membranes prepared from RINm5F rat insulinoma-derived cells using disuccinimidyl suberate. Consistent with the presence of a single class of binding site on the surface of intact cells, only a single radiolabelled band at Mr63,000 was identified by SDS-PAGE after solubilization of the ligand-binding protein complex. The band was not observed when 10nM glucagon-like peptide-1(7-36)amide was included in the binding assay, but 1 microM concentrations of glucagon-like peptide-1(1-36)amide, glucagon-like peptide-2 and glucagon did not decrease the intensity of labelling. No change in the mobility of the band was observed under reducing conditions, suggesting that the binding protein in the receptor is not attached to other subunits via disulphide bonds. In control incubations using plasma membranes from pig intestinal epithelial cells, which do not contain specific binding sites for glucagon-like peptide-1(7-36)amide, no cross-linked ligand-binding protein complex was observed.
Carbon-Halogen Bond Cleavage (1968)

Abstract Extracts of a pseudomonad isolated from soil have two halidohydrolases, one induced by chloroacetate, the other by dichloroacetate. Both enzymes have been partially purified and each catalyzes a variety of dehalogenations which conform to the general equation l-RCHXCOO- + OH- → d-RCHOHCOO- + X- where X = Cl or I. Like haloacetate halidohydrolase, these enzymes have a pH optimum of 9.0 to 9.4 and utilize the hydroxyl group from water to replace the halogen in the substrate. The inversion of the configuration which occurs during the dehalogenation of optically active substrates gives additional insight into the mechanism of this type of reaction.
Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium (2015)

Cystic fibrosis (CF) is a lethal genetic disorder most commonly caused by the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It is not readily amenable to gene therapy because of its systemic nature and challenges including in vivo gene delivery and transient gene expression. Here we use triplex-forming peptide nucleic acids and donor DNA in biodegradable polymer nanoparticles to correct F508del. We confirm modification with sequencing and a functional chloride efflux assay. In vitro correction of chloride efflux occurs in up to 25% of human cells. Deep-sequencing reveals negligible off-target effects in partially homologous sites. Intranasal delivery of nanoparticles in CF mice produces changes in the nasal epithelium potential difference assay, consistent with corrected CFTR function. Also, gene correction is detected in the nasal and lung tissue. This work represents facile genome engineering in vivo with oligonucleotides using a nanoparticle system to achieve clinically relevant levels of gene editing without off-target effects.
The purification and properties of human liver ketohexokinase. A role for ketohexokinase and fructose-bisphosphate aldolase in the metabolic production of oxalate from xylitol (1985)

Ketohexokinase (EC 2.7.1.3) was purified to homogeneity from human liver, and fructose-bisphosphate aldolase (EC 4.1.2.13) was partially purified from the same source. Ketohexokinase was shown, by column chromatography and polyacrylamide-gel electrophoresis, to be a dimer of Mr 75000. Inhibition studies with p-chloromercuribenzoate and N-ethylmaleimide indicate that ketohexokinase contains thiol groups, which are required for full activity. With D-xylulose as substrate, ketohexokinase and aldolase can catalyse a reaction sequence which forms glycolaldehyde, a known precursor of oxalate. The distribution of both enzymes in human tissues indicates that this reaction sequence occurs mainly in the liver, to a lesser extent in the kidney, and very little in heart, brain and muscle. The kinetic properties of ketohexokinase show that this enzyme can phosphorylate D-xylulose as readily as D-fructose, except that higher concentrations of D-xylulose are required. The kinetic properties of aldolase show that the enzyme has a higher affinity for D-xylulose 1-phosphate than for D-fructose 1-phosphate. These findings support a role for ketohexokinase and aldolase in the formation of glycolaldehyde. The effect of various metabolites on the activity of the two enzymes was tested to determine the conditions that favour the formation of glycolaldehyde from xylitol. The results indicate that few of these metabolites affect the activity of ketohexokinase, but that aldolase can be inhibited by several phosphorylated compounds. This work suggests that, although the formation of oxalate from xylitol is normally a minor pathway, under certain conditions of increased xylitol metabolism oxalate production can become significant and may result in oxalosis.
BizTalk Unleashed (2002)

From the Publisher:
BizTalk Unleashed covers a wide range of implementation and development tools, techniques, and technologies for use with BizTalk Server. You will learn everything from the basic foundation and history of XML to how to create, transform, process, and configure BizTalk server specifications, maps, and BizTalk Messaging.

Instead of just skimming the surface of what BizTalk Server has to offer, this book provides an overarching view of how BizTalk Server impacts the traditionally difficult application integration tasks developers face. Detailed information and example code is given on the new BizTalk 2002 features as well as the correlation of BizTalk Messaging and Orchestration services, the integration of .NET, and the RosettaNet and HIPPA BizTalk Server accelerators.
Glucagon and glucagon-like peptide 1: selective receptor recognition via distinct peptide epitopes. (1994)

Glucagon and glucagon-like peptide 1 (GLP-1) are homologous peptide hormones that are recognized by likewise homologous, but highly selective receptors. Analogs of glucagon and GLP-1, in which the divergent residues were systematically exchanged, were employed to identify the structural requirements for their selective receptor recognition. Substitutions in the NH2-terminal part of the glucagon molecule with the corresponding GLP-1 residues, as for example in [Ala2,Glu3]-glucagon and [Val10,Ser12]glucagon, reduced the binding affinity for the glucagon receptor several hundred-fold without increasing the affinity for the GLP-1 receptor. In contrast, introduction of GLP-1 residues into the far COOH-terminal part of the glucagon molecule, e.g. [Val27,Lys28,Gly29,Arg30]glucagon, had a minimal effect on recognition of the glucagon receptor, but improved the affinity of the analog for the GLP-1 receptor up to 200-fold. Similarly, substitutions in especially the far COOH-terminal part of the GLP-1 molecule with the corresponding glucagon residues, e.g. des-Arg30-[Met27,Asn28,Thr29]GLP-1, decreased the affinity for the GLP-1 receptor several hundred-fold (IC50 = 0.4-190 nM) without increasing the affinity for the glucagon receptor. Conversely, substitutions in the NH2-terminal part of the GLP-1 molecule impaired the affinity for the GLP-1 receptor only moderately. We conclude that the selective recognition of the glucagon and GLP-1 receptors is determined by residues located at opposite ends of the homologous peptide ligands. This conclusion is supported by the observation that a "chimeric" peptide consisting of the NH2-terminal part of the glucagon molecule joined to the COOH-terminal part of the GLP-1 molecule was recognized with high affinity by both receptors.