gebhart/patrepeval huggingface dataset:
Methylation Confers Accessibility, Stability and Selectivity to Picrotoxinin (2022)

Natural product total synthesis enables gain of function through deep-seated modification of structure. Synthetic difficulty can, however, obstruct meaningful optimization campaigns. To simplify access, the complexity of the target (TGT) can be lowered—a strategy described within function-oriented synthesis. Alternatively, the chemical space immediately surrounding the TGT can be searched for analogs of equal or greater complexity that also simplify access. This strategy—dynamic retrosynthetic analysis—maintains most physicochemical properties of the TGT (locus in chemical space) but opens new synthetic paths unavailable to the natural product itself and can provide functional advantage. Here we experimentally interrogate these ideas by generation of two parallel series of picrotoxinin (PXN) analogs to identify leads with ligand-gated ion channel (LGIC) selectivity. One series derives from PXN via semi-synthesis, and the other from 5MePXN via total synthesis. Methylation at C5 decreases potency against vertebrate ion channels (GABAa receptors) but maintains or increases antagonism of homologous invertebrate GABA-gated chloride channels (RDL receptors). Optimal 5MePXN analogs appear to change the PXN binding pose within GABAARs by disruption of a hydrogen bond network. The C5 methyl also stabilizes the scaffold substantially against irreversible C15 solvolysis by destabilizing an intermediate twist-boat conformer, which returns to 5MePXN instead of progressing to degradant. These discoveries are made possible by the lower synthetic burden of 5MePXN and are illuminated by the parallel analog series, which allows unambiguous identification of the role of the synthetically simplifying C5 methyl. Rapid access to functionally-privileged analogs by TGT point mutation underscores the value of dynamic retrosynthetic analysis as a problem-solving heuristic.
Abstract B209: A self-emulsifying lipid suspension formulation enhances oral bioavailability of MP-470 in a randomized two-way crossover study in healthy male subjects (2009)

Abstract Background: MP-470 is an orally bioavailable multi-targeted tyrosine kinase inhibitor specifically designed to be a potent inhibitor of mutant c-Kit and PDGFR. MP-470 is also active as an inhibitor of DNA repair following chemotherapy. MP-470 has shown significant synergistic activity with DNA damaging chemotherapy in several xenograft models and in a phase I combination study. Oral bioavailability of this agent is limited by its solubility but not permeability. An in vitro/in vivo iterative approach was utilized preclinically for formulation selection. In the Beagle dog model, the oral bioavailability of MP-470 is enhanced to a maximum of 4–5-fold by formulating it in tocopherols and lipidic surfactants with self-emulsification ability (5%, dry powder vs. 20%, lipid suspension). Results presented herein are from a randomized two-way crossover pharmacokinetic (PK) study evaluating two formulations in healthy human subjects. Methods: Twelve healthy male subjects 18–45 years with a body mass index of 18–35 kg/m2 were randomized in a 1:1 ratio to receive either a 100 mg dry powder capsule or 90 mg (3 × 30 mg) lipid suspension capsules in a fasted condition with 240 mL of water. Subjects receiving MP-470 90 mg lipid suspension capsules ingested all three capsules within one minute. The alternate formulation was administered after a 14 day washout. Plasma for PK assessments was collected and evaluated at pre-dose through hour 48 post MP-470 administration. Results: Comparative PK results from twelve subjects are summarized below. Additional information will be summarized in the final presentation. Conclusions: Solubility of the drug in the formulation vehicle alone plays a limited role in bioavailability enhancement; rather the ability of the formulation to keep the drug in solution after dilution in the GI tract seems critical. It is also possible that physiological mechanisms such as active transport or metabolism contribute to the enhanced absorption of MP-470 in the tocopherol-based vehicles. Consistent with preclinical Beagle dog data, the lipid suspension formulation offers an enhanced oral bioavailability over the dry powder formulation in healthy human subjects. The lipid suspension formulation will be utilized in future MP-470 clinical studies. Pharmacokinetic summary - Dry Powder vs. Lipid Suspension Capsules Parameters 100 mg MP-470 Dry Powder Average (CV, n=12) 90 mg MP-470 Lipid Suspension Average (CV, n=12) Average % Increase* (95% CI) Cmax (ng/mL) 23.2 (71%) 132.6 (55%) 635% (420%, 851%) Tmax (h) 4.1 (44%) 1.7 (54%) - AUClast (ng·h/mL) 253 (54%) 488 (40%) 131% (85%, 177%) Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B209.
Recycle slurry oil characterization. Final report, October 1980-March 1985 (1985)

This report includes results and interpretation of Conoco's analyses of process oils from Wilsonville Run 246 operated from April through August, 1984, in the DITSL and ITSL modes with Clovis Point subbituminous coal. Seventy-one samples were analyzed from Run 246. Characterization and interpretation of eight samples from HRI CTSL Run 227-18 (a scoping run) and twenty-five samples from HRI CTSL Run 227-20 (a demonstration run) are presented. Results are given from analysis of eleven distillate and eleven resid samples from Lummus Run 4LCF14 which tested the effects of LC-Finer conditions on recycle solvent quality. The molecular composition of a typical Lummus ITSL recycle distillate is presented. The reproducibility of several of our routine analytical and empirical methods is demonstrated. 15 refs., 17 figs., 45 tabs.
C3d binding to the circumsporozoite protein carboxy-terminus deviates immunity against malaria (2005)

The immunogenicity of recombinant protein or anti-viral DNA vaccines can be significantly improved by the addition of tandem copies of the complement fragment C3d. We sought to determine if the efficacy of a circumsporozoite protein (CSP)-based DNA vaccine delivered to mouse skin by gene gun was improved by using this strategy. Instead, we found that C3d suppressed the protective immunity against Plasmodium berghei malaria infection and deviated immunity, most notably by suppressing the induction of antibodies specific for the CSP C-terminal flanking sequence and by suppressing the induction of CSP-specific IL-4-producing spleen cells. We further showed that C3d bound to the C-terminal flanking sequence of the CSP, which may explain the immune deviation observed in CS/C3d chimeric antigen. We have thus identified C3d-mediated epitope masking and shifting of both the humoral and cellular immune responses as a potential novel escape mechanism, which plasmodia may use to divert the induction of protective immunity.
Guidelines for accreditation of endoscopy units: quality measures from the Korean Society of Coloproctology (2021)

The KSCP recommends that endoscopy units performing CRC screening evaluate 6 key performance measures during daily practice.
An Electrokinetic Testing Apparatus for Undisturbed/Remoulded Soils under In-Situ Stress Conditions (2000)

Abstract In this paper, the design and construction of an apparatus for the study of electrokinetics are presented in detail. The apparatus is capable of both applying a designated effective stress to a soil sample and measuring the volume change and pore pressure during the electrokinetic testing. The results of a high voltage electrokinetic test on a remolded natural clay sample are reported to illustrate the operation of the apparatus and to study the mechanism of high voltage electrokinetics. During the 91 day test period of, including the application of a high voltage (−10 kV to −12 kV) for 51 days via insulated electrodes, the volume and pore pressure changes were negligible. Nevertheless, the geotechnical properties of the soil significantly improved, including increases in shear strength (69%), shear modulus (151%) and preconsolidation pressure (700%). Since the increases are calculated with respect to the control sample under identical effective stress and drainage conditions over the same time period, they can only be attributed to high voltage electrokinetic effects, possibly cementation bonding, diagenesis, and ionic diffusion. The electrokinetic testing apparatus developed in this study provides a viable tool for the study of electrokinetics on clayey soils for better understanding of the mechanisms involved in the process.
Conversion of Methyl Radicals to Methanol and Formaldehyde over Molybdenum Oxide Catalysts (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConversion of Methyl Radicals to Methanol and Formaldehyde over Molybdenum Oxide CatalystsSergei Pak, Michael P. Rosynek, and Jack H. LunsfordCite this: J. Phys. Chem. 1994, 98, 45, 11786–11790Publication Date (Print):November 1, 1994Publication History Published online1 May 2002Published inissue 1 November 1994https://pubs.acs.org/doi/10.1021/j100096a025https://doi.org/10.1021/j100096a025research-articleACS PublicationsRequest reuse permissionsArticle Views183Altmetric-Citations22LEARN 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 options Get e-Alerts
S(O)‐Pixyl Protecting Group as Efficient Mass‐Tag. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Conformational Changes Spanning Angstroms to Nanometers via a Combined Protein-Induced Fluorescence Enhancement–Förster Resonance Energy Transfer Method (2017)

Förster resonance energy transfer (FRET)-based single-molecule techniques have revolutionized our understanding of conformational dynamics in biomolecular systems. Recently, a new single-molecule technique based on protein-induced fluorescence enhancement (PIFE) has aided studies in which minimal (<3 nm) displacements occur. Concerns have been raised regarding whether donor fluorophore intensity (and correspondingly fluorescence quantum yield Φ<sub>f</sub>) fluctuations, intrinsic to PIFE methods, may adversely affect FRET studies when retrieving the donor-acceptor dye distance. Here, we initially show through revisions of Förster's original equation that distances may be calculated in FRET experiments regardless of protein-induced intensity (and Φ<sub>f</sub>) fluctuations occurring in the donor fluorophore. We additionally demonstrate by an analysis of the recorded emission intensity and competing decay pathways that PIFE and FRET methods may be conveniently combined, providing parallel complementary information in a single experiment. Single-molecule studies conducted with Cy3- and ATTO647N-labeled RNA structures and the HCV-NS5B polymerase protein undergoing binding dynamics along the RNA backbone provide a case study to validate the results. The analysis behind the proposed method enables for PIFE and FRET changes to be disentangled when both FRET and PIFE fluctuate over time following protein arrival and, for example, sliding. A new method, intensity-FRET, is thus proposed to monitor conformational changes spanning from angstroms to nanometers.
Enhancing School-Based Asthma Education Efforts Using Computer-Based Education for Children (2012)

Educational games and other programs are effective methods of delivering knowledge about asthma management and control. Research about the long-term effects of this increased knowledge, in regard to behavior change, is needed. Additionally, developing sustainable projects, which are culturally relevant, is a goal for future research.
Catalytically Grown Carbon Nanotubes of Small Diameter Have a High Young's Modulus (2005)

Experimental studies of carbon nanotubes (CNTs) obtained through different synthesis routes show considerable variability in their mechanical properties. The strongest CNTs obtained so far had a high Young's modulus of 1 TPa but could only be produced in gram scale quantities. The synthesis by catalytic chemical vapor deposition, a method that holds the greatest potential for large-scale production, gives CNTs with a high defect density. This leads to low Young's modulus values below 100 GPa for multiwall CNTs. Here we performed direct measurements of the mechanical properties of catalytically grown CNTs with only a few walls and find a Young's modulus of 1 TPa. This high value is confirmed for CNTs grown under two different growth conditions where the synthesis parameters such as the hydrocarbon source, catalyst material, and the synthesis temperature were varied. The results indicate that the observed difference in the Young's modulus for the catalytically grown CNTs with high and low numbers of walls is probably related to the growth mechanism of CNT.
Valsartan and the Kidney: Present and Future (1999)

Angiotensin (Ang) II type 1 (AT1) receptor antagonists are orally active drugs that specifically block the subtype 1 of Ang receptors. In contrast to AT1 receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors block the actions of Ang II incompletely. Furthermore, the bradykinin-potentiating effects of ACE inhibitors may contribute to the mechanism of action of ACE inhibitors. Data in experimental animals suggest that AT1 receptor antagonists decrease the glomerular filtration rate (GFR) to a lesser degree than ACE inhibitors. The greater effect of ACE inhibitors in decreasing glomerular pressure was attenuated with a bradykinin antagonist. In rat models of renal damage with proteinuria, acute reduction of proteinuria was seen with ACE inhibitors but not with AT1 receptor antagonists, whereas long-term reductions of proteinuria were of similar magnitude with both agents. Renal histology after several months revealed that AT1 receptor antagonists and ACE inhibitors were equally renoprotective in various renal damage models. AT1 receptor antagonists, like ACE inhibitors, exhibit a natriuretic effect equal to moderate doses of a thiazide diuretic. In patients with severe volume depletion, use of AT1 receptor antagonists may lead to acute renal failure. Valsartan was tested in a double-blind trial in patients with moderate to severe renal failure and led to a substantial decrease in diastolic and systolic blood pressure, whereas there was no difference from placebo for changes in GFR. Urine protein increased with placebo and decreased with valsartan. The data indicate that valsartan in renal failure patients is effective in lowering blood pressure while leaving renal excretory function unaltered. Whether there is a renoprotective effect can only be shown in long-term trials, which are under way.
Parametric Regression on the Grassmannian (2015)

We address the problem of fitting parametric curves on the Grassmann manifold for the purpose of intrinsic parametric regression. As customary in the literature, we start from the energy minimization formulation of linear least-squares in Euclidean spaces and generalize this concept to general nonflat Riemannian manifolds, following an optimal-control point of view. We then specialize this idea to the Grassmann manifold and demonstrate that it yields a simple, extensible and easy-to-implement solution to the parametric regression problem. In fact, it allows us to extend the basic geodesic model to (1) a time-warped variant and (2) cubic splines. We demonstrate the utility of the proposed solution on different vision problems, such as shape regression as a function of age, traffic-speed estimation and crowd-counting from surveillance video clips. Most notably, these problems can be conveniently solved within the same framework without any specifically-tailored steps along the processing pipeline.
A Micro-expression Recognition Algorithm for Students in Classroom Learning Based on Convolutional Neural Network (2019)

In classroom teaching, the teachers should adjust the teaching strategy and improve the teaching effect based on the expression and learning state of each student. This paper mainly develops a micro-expression recognition algorithm for students in classroom learning, based on convolutional neural network (CNN) and automatic face detection. Specifically, the multitask deep convolution network (DNN) was adopted to detect the landmark points of human face, and a hybrid DNN was designed to extract the optical-flow features of micro-expression. The extracted features were improved through redundancy removal and dimensionality reduction. The rationality of our algorithm was proved through a comparative experiment on real-world databases and an application in classroom teaching. The research results provide a new direction for applying deep learning in face recognition.
Sequences and expression of alleles of polymorphic arylamine N-acetyltransferase of human liver. (1992)

Fifty human livers obtained at autopsy were analyzed for N-acetyltransferase and classified into six genotypes. Determination of N-acetyltransferase activity and proteins from supernatants of liver homogenates indicate that genotype I corresponds to rapid acetylator, genotypes II and III to intermediate acetylator, and genotypes IV, V, and VI to slow acetylator phenotypes. Northern blot analysis shows that levels of mRNA for N-acetyltransferase in the livers do not markedly differ among the six genotypes. Three alleles of the N-acetyltransferase gene were cloned and sequenced. mRNA is coded in two exons. Comparison of alleles 2 and 3, which correspond to low N-acetyltransferase activity, with allele 1, which corresponds to high N-acetyltransferase activity, revealed several polymorphisms. Two gene sequence differences occur in the coding exons of alleles 2 and 3, one of which would produce different amino acids in the proteins. Those sequence differences that lead to amino acid substitutions result in a loss of BamHI and TaqI sites for alleles 2 and 3, respectively. Expression studies of the alleles in Chinese hamster ovary cells show that allele 1 expresses high levels of N-acetyltransferase activity and enzyme protein, while alleles 2 and 3 express low levels of both protein and activity.
Hydrogenated ultra-thin tin films predicted as two-dimensional topological insulators (2014)

10.1088/1367-2630/16/11/115008
Tuning the Drug Release from Antibacterial Polycaprolactone/Rifampicin-Based Core–Shell Electrospun Membranes: A Proof of Concept (2022)

The employment of coaxial fibers for guided tissue regeneration can be extremely advantageous since they allow the functionalization with bioactive compounds to be preserved and released with a long-term efficacy. Antibacterial coaxial membranes based on poly-ε-caprolactone (PCL) and rifampicin (Rif) were synthesized here, by analyzing the effects of loading the drug within the core or on the shell layer with respect to non-coaxial matrices. The membranes were, therefore, characterized for their surface properties in addition to analyzing drug release, antibacterial efficacy, and biocompatibility. The results showed that the lower drug surface density in coaxial fibers hinders the interaction with serum proteins, resulting in a hydrophobic behavior compared to non-coaxial mats. The air-plasma treatment increased their hydrophilicity, although it induced rifampicin degradation. Moreover, the substantially lower release of coaxial fibers influenced the antibacterial efficacy, tested against <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, and <i>Pseudomonas aeruginosa</i>. Indeed, the coaxial matrices were inhibitory and bactericidal only against <i>S. aureus</i>, while the higher release from non-coaxial mats rendered them active even against <i>E. coli</i>. The biocompatibility of the released rifampicin was assessed too on murine fibroblasts, revealing no cytotoxic effects. Hence, the presented coaxial system should be further optimized to tune the drug release according to the antibacterial effectiveness.
Chromate-free corrosion resistant conversion coatings for aluminum (1993)

We have developed a method for generating chromate-free corrosion resistant coatings on aluminum alloys using a process procedurally similar to standard chromate conversion. These coatings provide good corrosion resistance on 6061-T6 and 1100 A1 under salt spray testing conditions. The resistance of the new coating is comparable to that of chromate conversion coatings in four point probe tests, but higher when a mercury probe technique is used. Initial tests of paint adhesion, and under paint corrosion resistance are promising. Primary advantage of this new process is that no hazardous chemicals are used or produced during the coating operation.
Membership in a Surgical Specialty Organization Is a Better Predictor of High-Volume Surgeons and Hospitals Than Specialty Training Pathway for Endocrine Operations (2019)

Kuo, Jennifer H. MD, MS, FACS; Duh, Quan-Yang MD, FACS; Chen, Herbert MD, FACS; Chabot, John A. MD, FACS; Lee, James A. MD, FACS Author Information
Measuring viscoelastic properties with in-situ ultrasonically induced microbubbles (2008)

A preliminary study on new bubble-mediated microenvironment viscoelastic imaging technique using our novel contrast agent phase-change nano droplet is performed. Apparent difference is observed among acoustic signals obtained from gel phantoms with difference in elastic properties at the timing of phase change induction. In particular, frequency of responding motion to impulse (f <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">res</inf> ) exhibited high correlation with gel's elastic properties between Young's modulus of 10 – 39 kPa. Furthermore, other parameters such as magnitude of phase change are influenced by change in gel's polyacrylamide concentration, possibly due to change in both elasticity and viscosity. These results suggest that PCND is a promising tool for characterizing microenvironment tissue viscoelastic properties.