gebhart/patrepeval huggingface dataset:
A Novel Approach to the Study of Solution Structures and Dynamic Behavior of Paclitaxel and Docetaxel Using Fluorine-Containing Analogs as Probes (1997)

Three fluorine-containing paclitaxel and docetaxel analogs, 3'-dephenyl-3'-(4-fluorophenyl)-3'N-debenzoyl-3'N-(4-fluorobenzoyl)paclitaxel (3), 3'-dephenyl-3'-(4-fluorophenyl)docetaxel (4), and 2',10-diacetyl-3'-dephenyl-3'-(4-fluorophenyl)docetaxel (5), are prepared and used as probes for the conformational analysis of paclitaxel and docetaxel in aqueous and nonaqueous solvent systems. The dependence of the 19F chemical shifts and the JH2'-H3' values of these fluorinated analogs is examined through 19F and 1H variable temperature (VT) NMR measurements. The experiments clearly indicate highly dynamic behavior of these molecules and the existence of equilibrium between conformers, especially in protic solvents, i.e., DMSO-d6/D2O, CH3OD/D2O, and CH3OD, which have not clearly been recognized by the previous studies. The analysis of the VT NMR data in combination with molecular modeling including restrained molecular dynamics (RMD) has identified three key conformers, A, B, and C, in which conformer C possesses rather unusual nearly eclipsed arrangements at the C2'−C3' bond. Conformers A and C are essentially the same as those identified by X-ray analysis of docetaxel and paclitaxel, respectively. RMD evaluation of conformer C in a simulated aqueous environment shows substantial stabilization of this conformer in protic solvents as compared to the other conformers. The 19F−1H heteronuclear NOE measurements of these fluoro analogs also support the structures of the three conformers. Conformers B and C form a hydrophobic clustering among the 4-fluorophenyl at C-3', the phenyl at the C-2 benzoate, and the methyl at the C-4 acetate moieties. Since conformer C appears to be the predominant molecular structure at ambient temperature in aqueous solvents, this conformer is likely to be the molecular structure of paclitaxel or docetaxel that is recognized at the tubulin binding site. This study has unambiguously demonstrated the usefulness of these "fluorine probes" for the solution structures and dynamic behavior of complex molecules such as paclitaxel and docetaxel.
Meeting Abstracts of the BACR conference: response and resistance in cancer therapy (2018)

Cancer Drug Resistance is an open access journal, focusing on pharmacological aspects of drug resistance and its reversal, molecular mechanisms of drug resistance and drug classes, etc. Both clinical and experimental aspects of drug resistance in cancer are included.
Intraepidermal Nerve Fibers Are Indicators of Small-Fiber Neuropathy in Both Diabetic and Nondiabetic Patients (2004)

IENF was not significantly altered in these patients at <5 years' duration of diabetes, but fell significantly after 5 years of diabetes. MDL exhibited a linear loss with time, suggesting a different mechanism of change. MDL and IENF together may prove a useful end point in therapeutic trials for neuropathy.
Newer Is Sometimes Better (2015)

The popular Network File System (NFS) protocol is 30 years old. The latest version, NFSv4, is more than ten years old but has only recently gained stability and acceptance. NFSv4 is vastly different from its predecessors: it offers a stateful server, strong security, scalability/WAN features, and callbacks, among other things. Yet NFSv4's efficacy and ability to meet its stated design goals had not been thoroughly studied until now. This paper compares NFSv4.1's performance with NFSv3 using a wide range of micro- and macro-benchmarks on a testbed configured to exercise the core protocol features. We (1) tested NFSv4's unique features, such as delegations and statefulness; (2) evaluated performance comprehensively with different numbers of threads and clients, and different network latencies and TCP/IP features; (3) found, fixed, and reported several problems in Linux's NFSv4.1 implementation, which helped improve performance by up to 11X; and (4) discovered, analyzed, and explained several counter-intuitive results. Depending on the workload, NFSv4.1 was up to 67\% slower than NFSv3 in a low-latency network, but exceeded NFSv3's performance by up to 2.9X in a high-latency environment. Moreover, NFSv4.1 outperformed NFSv3 by up to 172X when delegations were used.
Water Overcomes Methyl Group Directing Effects in Epoxide-Opening Cascades (2009)

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionWater Overcomes Methyl Group Directing Effects in Epoxide-Opening CascadesChristopher J. Morten and Timothy F. Jamison*Cite this: J. Am. Chem. Soc. 2009, 131, 26, 9463Publication Date (Web):June 1, 2009Publication History Published online1 June 2009Published inissue 8 July 2009https://pubs.acs.org/doi/10.1021/ja903581chttps://doi.org/10.1021/ja903581ccorrectionACS PublicationsCopyright © 2009 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views2015Altmetric-Citations2LEARN 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 PDF (60 KB) Get e-AlertscloseSUBJECTS:Alkyls Get e-Alerts
The miR-185/PAK6 axis predicts therapy response and regulates survival of drug-resistant leukemic stem cells in CML (2020)

Overcoming drug resistance and targeting cancer stem cells remain challenges for curative cancer treatment. To investigate the role of microRNAs (miRNAs) in regulating drug resistance and leukemic stem cell (LSC) fate, we performed global transcriptome profiling in treatment-naive chronic myeloid leukemia (CML) stem/progenitor cells and identified that miR-185 levels anticipate their response to ABL tyrosine kinase inhibitors (TKIs). miR-185 functions as a tumor suppressor: its restored expression impaired survival of drug-resistant cells, sensitized them to TKIs in vitro, and markedly eliminated long-term repopulating LSCs and infiltrating blast cells, conferring a survival advantage in preclinical xenotransplantation models. Integrative analysis with mRNA profiles uncovered PAK6 as a crucial target of miR-185, and pharmacological inhibition of PAK6 perturbed the RAS/MAPK pathway and mitochondrial activity, sensitizing therapy-resistant cells to TKIs. Thus, miR-185 presents as a potential predictive biomarker, and dual targeting of miR-185-mediated PAK6 activity and BCR-ABL1 may provide a valuable strategy for overcoming drug resistance in patients.
Tangram (2019)

Resource control in heterogeneous computers built with subsystems from different vendors is challenging. There is a tension between the need to quickly generate local decisions in each subsystem and the desire to coordinate the different subsystems for global optimization. In practice, global coordination among subsystems is considered hard, and current commercial systems use centralized controllers. The result is high response time and high design cost due to lack of modularity.
Immunogenetics of the Host Response to Viral Infections (2014)

This chapter reviews the main steps of the adaptive immune responses and discusses the consequences of genetic polymorphism for the susceptibility to viral infections. It also reviews recent important results obtained with particular viral infections of mice and of humans and concludes with some general remarks on the consequences of these studies for both our fundamental understanding of viral pathogenesis and practical applications to human medicine. Extensive polymorphism of class I and class II molecules, the number of alleles, and their heterozygosity account for the ability to mount efficient immune responses against a large variety of infectious agents. Nevertheless, the modulation of the immune response to viruses by the major histocompatibility complex (MHC) haplotype is well documented for mice and other laboratory animals. The Mx genes and their protein products constitute one of the best-characterized systems of genetically regulated control of viral infections. Importantly, the effect of the Mx1 gene on resistance was not mediated by the adaptive immune responses but was dependent on alpha/beta interferon. A better comprehension of the genetic control of virus infections will help us understand not only how we have evolved but also what we can and cannot achieve with antiviral drugs and vaccines.
Birational morphisms of the plane (2003)

Let A^2 be the affine plane over a field K of characteristic 0. Birational morphisms of A^2 are mappings A^2 \to A^2 given by polynomial mappings ϕof the polynomial algebra K[x,y] such that for the quotient fields, one has K(ϕ(x), ϕ(y)) = K(x,y). Polynomial automorphisms are obvious examples of such mappings. Another obvious example is the mapping τ_x given by x \to x, y \to xy. For a while, it was an open question whether every birational morphism is a product of polynomial automorphisms and copies of τ_x. This question was answered in the negative by P. Russell (in an informal communication). In this paper, we give a simple combinatorial solution of the same problem. More importantly, our method yields an algorithm for deciding whether a given birational morphism can be factored that way.
Slurry Activation for Enhanced Surface Redox Reactions in CMP (2023)

A novel add-on hardware device is placed near the point of slurry dispense that can instantaneously activate slurry performance during polishing via megasonic irradiation. This new technology (Flucto-CMP® is able to overcome the inherent polisher-slurry weaknesses such as wafer-level defects, process vibrations, cost of ownership, slurry waste, remval rate (RR), and RR selectivity. Flucto-CMP® has been successfully applied to various types of CMP slurries resulting in significant increases in the removal rates of copper, SiC, borosilicate hard mask, ILD, TiN, and silicon carbide through chemical alteration of the passivation layer needed for material removal. Specifically, for copper CMP, using Flucto-CMP®, we see an up to 31% boost in RR which is well correlated with the amount of reactive oxidizing species generated through irradiation as well as the measured relative indentation depth of the passivation layer. In addition to boosts in RR, for copper, we see a 50X drop in the variance of shear force and a 5X drop in the variance of normal force when Flucto-CMP® is used. This dramatic reduction in process vibration for copper soft-landing processes ought to reduce wafer-level defects. Much greater rate improvements are observed when polishing SiC, and borosilicate hard masks.
Involvement of the Arg179 in the active site of human IL‐6 (1993)

Three internal-amino acid deletions of amino acids 171-179 of human interleukin 6 (IL-6) were introduced at the cDNA level. While all deletion proteins were biologically inactive, immunoprecipitations with a set of conformation-specific anti-(IL-6) monoclonal antibodies showed that only mutant delta 177-179 does not present major alterations in folding. This finding, together with the observation that delta 177-179 is not able to compete with IL-6 for binding to the soluble human IL-6 receptor, suggested that some or all of these three residues participate to the composition of the receptor-binding site of human IL-6. A large number of single-amino-acid-substitution mutants were generated in residues 177, 178 and 179. Their detailed analysis revealed that Arg179 is crucial for activity in mouse cells, because all amino acid substitutions in this position cause a dramatic drop of biological activity on murine hybridoma cells without affecting the overall protein folding. The only substitution which preserved some residual activity was the conservative Arg to Lys change. This demonstrates the absolute requirement for a positive charge in position 179 for the interaction of human IL-6 with its receptor.
Discovery and SAR of Novel 2,3‐Dihydroimidazo[1,2‐c]quinazoline PI3K Inhibitors: Identification of Copanlisib (BAY 80‐6946) (2016)

The phosphoinositide 3-kinase (PI3K) pathway is aberrantly activated in many disease states, including tumor cells, either by growth factor receptor tyrosine kinases or by the genetic mutation and amplification of key pathway components. A variety of PI3K isoforms play differential roles in cancers. As such, the development of PI3K inhibitors from novel compound classes should lead to differential pharmacological and pharmacokinetic profiles and allow exploration in various indications, combinations, and dosing regimens. A screening effort aimed at the identification of PI3Kγ inhibitors for the treatment of inflammatory diseases led to the discovery of the novel 2,3-dihydroimidazo[1,2-c]quinazoline class of PI3K inhibitors. A subsequent lead optimization program targeting cancer therapy focused on inhibition of PI3Kα and PI3Kβ. Herein, initial structure-activity relationship findings for this class and the optimization that led to the identification of copanlisib (BAY 80-6946) as a clinical candidate for the treatment of solid and hematological tumors are described.
Genetically-Encoded Discovery of Perfluoroaryl-Macrocycles that Bind to Albumin and Exhibit Extended Circulation in-vivo (2022)

Abstract In this paper, we report selection of albumin-binding macrocyclic peptides from genetically encoded libraries of peptides modified by perfluoroaryl-cysteine S N Ar chemistry. Modification of phage-displayed libraries SXCX n C-phage, n =3–5, where X is any amino acid except for cysteine by decafluoro-diphenylsulfone ( DFS ), yields genetically-encoded library of octafluoro-diphen-ylsulfone-crosslinked macrocycles ( OFS -SXCX n C-phage). Selection from these libraries using albumin as a bait identified a family of significantly enriched perfluoroaryl-macrocycles. Synthesis of perfluoroaryl-macrocycles predicted by phage display and testing their binding properties by 19 F NMR and fluorescent polarization identified OFS -macrocycle with SICRFFC sequence as the most potent albumin binder. We observed that OFS -macrocycles slowly react with biological nucleophiles such as glutathione. Replacing decafluoro-diphenylsulfone by nearly isosteric pentafluorophenyl sulfide yielded perfluorophenylsulfide ( PFS )-crosslinked macrocycles devoid of undesired reactivity. The augmented lead PFS -macrocycle with SICRFFC sequence exhibited K D = 4–6 μM towards human serum albumin and similar affinities towards rat and mouse albumins. When injected in mouse, the PFS -SICRFFCGGG compound was significantly retained in circulation in vivo when compared to control PFS -macrocyclic peptide. The perfluoroaryl-macrocycles with SICRFFC motif are the smallest known peptide macrocycle with significant affinity for human albumin and they are a productive starting point for future development of compact macrocycles with predictable circulation half-life in vivo .
Hypervalent Iodine Compounds as Versatile Reagents for Extremely Efficient and Reversible Patterning of Graphene with Nanoscale Precision (2021)

Rational patterning and tailoring of graphene relies on the disclosure of suitable reagents for structuring the target functionalities on the 2D-carbon network. Here, a series of hypervalent iodine compounds, namely, 1-chloro-1,2-benziodoxol-3(1H)-one, 1,3-dihydro-1-hydroxy-3,3-dimethyl-1,2-benziodoxole, and 3,3-dimethyl-1-(trifluoromethyl)-1,2-benziodoxole is reported to be extremely efficient for a diversified graphene patterning. The decomposition of these compounds generates highly reactive Cl, OH, and CF<sub>3</sub> radicals exclusively in the irradiated areas, which subsequently attach onto the graphene leading to locally controlled chlorination, hydroxylation, and trifluoromethylation, respectively. This is the first realization of a patterned hydroxylation of graphene, and the degrees of functionalization of the patterned chlorination and trifluoromethylation are both unprecedented. The usage of these mild reagents here is reasonably facile compared to the reported methods using hazardous Cl<sub>2</sub> or ICl and allows for sophisticated pattern designs with nanoscale precision, promising for arbitrary nanomanipulation of graphene's properties like hydrophilicity and conductivity by the three distinct functionalities (Cl, OH, and CF<sub>3</sub> ). Moreover, the attachment of functional entities to these highly functionalized graphene nanoarchitectures is fully reversible upon thermal annealing, enabling a full writing/storing/reading/erasing control over the chemical information stored within graphene. This work provides an exciting clue for target 2D functionalization and modulation of graphene by using suitable hypervalent iodine compounds.
An algebraic framework for edge-disjoint permutations on hypercubes (2003)

The operation of permuting data among the vertices of a hypercube computer induces a set of paths from senders to receivers. Permutations with edge-disjoint paths are desirable for efficient communication. The authors give simple algebraic descriptions for large classes of permutations that induce edge-disjoint paths for the commercially popular 'e-cube' routing algorithm. The descriptions cover most useful edge-disjoint permutations, and are easily applied in practice. Many previous proofs in the literature that specific permutations are edge-disjoint fall out as simple corollaries of the present work. Some new applications of this framework are presented. The first application considered concerns Gray code embeddings: the others are motivated by the connection of the present results to switching networks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Analysis and Predictive Modeling of Body Language Behavior in Dyadic Interactions from Multimodal Interlocutor Cues (2014)

During dyadic interactions, participants adjust their behavior and give feedback continuously in response to the behavior of their interlocutors and the interaction context. In this paper, we study how a participant in a dyadic interaction adapts his/her body language to the behavior of the interlocutor, given the interaction goals and context. We apply a variety of psychology-inspired body language features to describe body motion and posture. We first examine the coordination between the dyad's behavior for two interaction stances: friendly and conflictive. The analysis empirically reveals the dyad's behavior coordination, and helps identify informative interlocutor features with respect to the participant's target body language features. The coordination patterns between the dyad's behavior are found to depend on the interaction stances assumed. We apply a Gaussian-Mixture-Model-based (GMM) statistical mapping in combination with a Fisher kernel framework for automatically predicting the body language of an interacting participant from the speech and gesture behavior of an interlocutor. The experimental results show that the Fisher kernel-based approach outperforms methods using only the GMM-based mapping, and using the support vector regression, in terms of correlation coefficient and RMSE. These results suggest a significant level of predictability of body language behavior from interlocutor cues.
Inhibition of Prolyl Hydroxylase Domain-Containing Protein Suppressed Lipopolysaccharide-Induced TNF-α Expression (2009)

PHD inhibition by DMOG or RNA interference inhibited LPS-induced TNF-alpha upregulation in macrophages possibly through NF-kappaB inhibition, which is independent of HIF-1alpha accumulation. This study suggests that PHDs are positive regulators of LPS-induced inflammatory process, and therefore inhibition of PHD may be a novel strategy for the treatment of inflammatory diseases.
Concentration dependence of shear and extensional rheology of polymer solutions: Brownian dynamics simulations (2006)

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation Christopher Stoltz, Juan J. de Pablo, Michael D. Graham; Concentration dependence of shear and extensional rheology of polymer solutions: Brownian dynamics simulations. J. Rheol. 1 March 2006; 50 (2): 137–167. https://doi.org/10.1122/1.2167468 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentThe Society of RheologyJournal of Rheology Search Advanced Search |Citation Search
Heat equation inversion framework for average SAR calculation from magnetic resonance thermal imaging (2016)

Deposition of radiofrequency (RF) energy can be quantified via electric field or temperature change measurements. Magnetic resonance imaging has been used as a tool to measure three dimensional small temperature changes associated with RF radiation exposure. When duration of RF exposure is long, conversion from temperature change to specific absorption rate (SAR) is nontrivial due to prominent heat-diffusion and conduction effects. In this work, we demonstrated a method for calculation of SAR via an inversion of the heat equation including heat-diffusion and conduction effects. This method utilizes high-resolution three dimensional magnetic resonance temperature images and measured thermal properties of the phantom to achieve accurate calculation of SAR. Accuracy of the proposed method was analyzed with respect to operating frequency of a dipole antenna and parameters used in heat equation inversion. Bioelectromagnetics. 37:493-503, 2016. © 2016 Wiley Periodicals, Inc.
Abstract 633: Unique AF-Specific Symptom Score Assesses Long-Term Symptom Relief After Ablation (2008)

Introduction: Ablation is indicated in pts with highly symptomatic atrial fibrillation (AF). While trials of ablation report favorable rhythm and quality of life (QoL) outcomes, corroborative data ...