gebhart/patrepeval huggingface dataset:
Synthesis of Eight Stereoisomers of Pochonicine: Nanomolar Inhibition of β-N-Acetylhexosaminidases (2013)

Pochonicine, the first naturally occurring polyhydroxylated pyrrolizidine containing an acetamidomethyl group, which was isolated from Pochonia suchlasporia var. suchlasporia TAMA 87, together with its enantiomer and their C-1 and/or C-3 epimers, have been synthesized from the sugar-derived cyclic nitrones 9D and 9L, respectively. An in-depth NMR study showed that both the (1)H and (13)C NMR spectra of the synthetic pochonicines (1D and 1L) matched very well with those of natural pochonicine in D2O, which unequivocally determined the relative configuration of the natural product as 1D or 1L. In addition, comparison of the optical rotations of the synthetic pochonicines and that of the natural product, but more convincingly their glycosidase inhibition profiles, confirmed the absolute configuration of natural pochonicine as 1R,3S,5R,6R,7S,7aR. Thereby, the structure of natural pochonicine was unequivocally determined as (+)-(1R,3S,5R,6R,7S,7aR)-pochonicine (1D). Glycosidase inhibition experiments showed that natural pochonicine 1D and its epimers 2D, 3D, and 4D all are powerful inhibitors of hexosaminidases (five β-N-acetylglucosaminidases and two β-N-acetylgalactosaminidases) while their enantiomers 1L, 2L, 3L, and 4L are much weaker inhibitors of the same enzymes. (-)-3-epi-Pochonicine (2L) was found to be a potent and selective inhibitor of α-l-rhamnosidase. None of the compounds showed any inhibition of α-GalNAcase.
High susceptibility of MDR and XDR Gram-negative pathogens to biphenyl-diacetylene-based difluoromethyl-allo-threonyl-hydroxamate LpxC inhibitors (2016)

These in vitro data highlight the therapeutic potential of the new LpxC inhibitor LPC-058 against MDR/XDR strains and set the stage for subsequent in vivo studies.
Progress in Quantitative Viral Load Testing: Variability and Impact of the WHO Quantitative International Standards (2016)

It has been hoped that the recent availability of WHO quantitative standards would improve interlaboratory agreement for viral load testing; however, insufficient data are available to evaluate whether this has been the case. Results from 554 laboratories participating in proficiency testing surveys for quantitative PCR assays of cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK virus (BKV), adenovirus (ADV), and human herpesvirus 6 (HHV6) were evaluated to determine overall result variability and then were stratified by assay manufacturer. The impact of calibration to international units/ml (CMV and EBV) on variability was also determined. Viral loads showed a high degree of interlaboratory variability for all tested viruses, with interquartile ranges as high as 1.46 log<sub>10</sub> copies/ml and the overall range for a given sample up to 5.66 log<sub>10</sub> copies/ml. Some improvement in result variability was seen when international units were adopted. This was particularly the case for EBV viral load results. Variability in viral load results remains a challenge across all viruses tested here; introduction of international quantitative standards may help reduce variability and does so more or less markedly for certain viruses.
More Than Structural Cells, Fibroblasts Create and Orchestrate the Tumor Microenvironment (2006)

The tumor microenvironment comprises many cell types including infiltrating immune cells such as lymphocytes, endothelial cells and a complex stroma consisting mainly of fibroblasts. Fibroblasts are heterogeneous and consist of Thy-1+ and Thy-1- subsets that define different biosynthetic and differentiation potential. They produce mediators linked to carcinogenesis and metastasis, including Cox-2 and PGE2, both of which are also increased in most cancers. This review will highlight the emerging role of the complex fibroblastic stroma in establishing a microenvironment supporting malignant transformation, tumor growth and attenuation of host anti-tumor immune responses.
Metareasoning in Modular Software Systems: On-the-Fly Configuration\n using Reinforcement Learning with Rich Contextual Representations (2019)

Assemblies of modular subsystems are being pressed into service to perform\nsensing, reasoning, and decision making in high-stakes, time-critical tasks in\nsuch areas as transportation, healthcare, and industrial automation. We address\nthe opportunity to maximize the utility of an overall computing system by\nemploying reinforcement learning to guide the configuration of the set of\ninteracting modules that comprise the system. The challenge of doing\nsystem-wide optimization is a combinatorial problem. Local attempts to boost\nthe performance of a specific module by modifying its configuration often leads\nto losses in overall utility of the system's performance as the distribution of\ninputs to downstream modules changes drastically. We present metareasoning\ntechniques which consider a rich representation of the input, monitor the state\nof the entire pipeline, and adjust the configuration of modules on-the-fly so\nas to maximize the utility of a system's operation. We show significant\nimprovement in both real-world and synthetic pipelines across a variety of\nreinforcement learning techniques.\n
Transfer of a mutant dihydrofolate reductase gene into pre- and postimplantation mouse embryos by a replication-competent retrovirus vector (1989)

In order to explore the potential of retrovirus vectors for efficiently transferring foreign genes into mouse embryos, a replication-competent recombinant Moloney murine leukemia virus (Mo-MLV) vector carrying a mutant dihydrofolate reductase (DHFR) cDNA insert in the U3 region of the viral long terminal repeat was used to infect pre- and postimplantation embryos. When preimplantation mouse embryos were infected with the vector, as expected, the provirus integrated into the embryos and the germ line with the same efficiency as that observed with wild-type Mo-MLV, leading to inactivation of the recombinant virus. In contrast, when postimplantation mouse embryos were microinjected with virus-producing cells, between 90 to 100% of the surviving animals proved to be infected with the virus. The recombinant virus spread as efficiently as wild-type Mo-MLV in the infected embryos, resulting in up to three to five proviral copies per genome in heart, thymus, and brain tissues. Substantial expression of mutant DHFR*-coding viral message was found in all somatic tissues analyzed, the amounts correlating with the proviral copy number in the respective organ. These results suggest that replication-competent vectors are useful for efficient transfer and expression of foreign genes into tissues or whole animals when virus spread is needed.
Attosecond science: Symbiosis of electrons and light (2011)

The symbiosis of electrons and light forms the basis of life: The microscopic motion of electrons creates light which supplies our globe with life-giving energy from the sun. Electrons transform light into biological energy during photosynthesis and into biological signals endowing us with the capability of seeing the world around us. Upon their motion inside and between atoms electrons emit light, carry and process information in biological systems and man-made devices, create, destroy, or modify molecules and thereby affect biological function. Consequently, they are key players in physical, chemical or life sciences as well as information, industrial and medical technologies likewise.
Oligomerization of CXCL10 Is Necessary for Endothelial Cell Presentation and In Vivo Activity (2006)

The chemokine IFN-gamma-inducible protein of 10 kDa (IP-10; CXCL10) plays an important role in the recruitment of activated T lymphocytes into sites of inflammation by interacting with the G protein-coupled receptor CXCR3. IP-10, like other chemokines, forms oligomers, the role of which has not yet been explored. In this study, we used a monomeric IP-10 mutant to elucidate the functional significance of oligomerization. Although monomeric IP-10 had reduced binding affinity for CXCR3 and heparin, it was able to induce in vitro chemotaxis of activated T cells with the same efficacy as wild-type IP-10. However, monomeric IP-10 was unable to induce recruitment of activated CD8+ T cells into the airways of mice after intratracheal instillation. Use of a different IP-10 mutant demonstrated that this inability was due to lack of oligomerization rather than reduced CXCR3 or heparin binding. Molecular imaging demonstrated that both wild-type and monomeric IP-10 were retained in the lung after intratracheal instillation. However, in vitro binding assays indicated that wild-type, but not monomeric, IP-10 was retained on endothelial cells and could induce transendothelial chemotaxis of activated T cells. We therefore propose that oligomerization of IP-10 is required for presentation on endothelial cells and subsequent transendothelial migration, an essential step for lymphocyte recruitment in vivo.
Diagnostic Accuracy of Intraoperative Techniques for Margin Assessment in Breast Cancer Surgery (2016)

Pooled data suggest that frozen section and cytology have the greatest diagnostic accuracy. However, these methods are resource intensive and turnaround times for results have prevented widespread international adoption. Emerging technologies need to compete with the diagnostic accuracy of existing techniques while offering advantages in terms of speed, cost, and reliability.
Environmental Degradation of Heat-Resistant Alloys During Exposure to Simulated and Actual Gas Turbine Recuperator Environments (2008)

Primary surface recuperators (PSR’s) for land-based industrial gas turbines are typically constructed from heat-resistant alloys such as nickel-base superalloys or highly-alloyed austenitic stainless steels. The water vapor present in gas turbine exhaust has been shown to increase the rate of chromium oxide volatility, which in turn can cause rapid oxidation of the underlying metal. As PSR’s are generally fabricated from thin foil materials, excessive degradation can cause perforation, leading to failure of components. The results of a field test program will be summarized, based on analysis of recuperator stand-in components which were exposed to a full-flow exhaust stream during gas turbine operation for times ranging from 500 hours to 21,500 hours. A significant effect of service on the materials of construction was observed, with near-surface chromium depletion and microstructural instability evident after the longest exposures. These results will be combined with those from an extensive laboratory test program to evaluate the performance of heat-resistant alloys during recuperator service, outlining the different modes of degradation and means for their mitigation.
ELLIPTICITY ANALYSIS OF THE BOOMERanG CMB MAPS (2003)

The properties of the Cosmic Microwave Background (CMB) maps carry valuable cosmological information. Here we report the results of the analysis hot and cold CMB anisotropy spots in the BOOMERanG 150 GHz map in terms of number, area, ellipticity, vs. temperature threshold. We carried out this analysis for the map obtained by summing independent measurement channels (signal plus noise map) and for a comparison map (noise only map) obtained by differencing the same channels. The anisotropy areas (spots) have been identified for both maps for various temperature thresholds and a catalog of the spots has been produced. The orientation (obliquity) of the spots is random for both maps. We computed the mean elongation of spots obtained from the maps at a given temperature threshold using a simple estimator. We found that for the sum map there is a region of temperature thresholds where the average elongation is not dependent on the threshold. Its value is ∼ 2.3 for cold areas and ∼ 2.2 for hot areas. This is a non-trivial result. The bias of the estimator is � +0.4 for areas of size � 30 ′ , and smaller for larger areas. The presence of noise also biases the ellipticity by � +0.3. These biases have not been subtracted in the results quoted above. The
ChemInform Abstract: An Improved Method for the Palladium‐Catalyzed Amination of Aryl Triflates. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Nonsteroidal Anti-inflammatory Drug Use Associated with Reduced Incidence of Adenocarcinomas of the Esophagus and Gastric Cardia that Overexpress Cyclin D1 (2004)

This study was undertaken to determine whether selected risk factors for esophageal and gastric cancer are associated with tumors that overexpress cyclin D1. Archived tumor tissue was available for 630 esophageal and gastric cancer patients who participated in a population-based case-control study. Patients were categorized into case groups based on whether protein overexpression of the cyclin D1 gene, as assessed by immunohistochemistry, was present (cyclin D1+, n = 285) or not (cyclin D1-, n = 345) in the tumor. The distribution of risk factors in each of these case groups was then compared with the distribution among the 695 controls. Multivariate-adjusted odds ratios (OR) for esophageal adenocarcinoma were reduced in relation to use of aspirin and other nonsteroidal anti-inflammatory drug (NSAID) use but only among patients with cyclin D1+ tumors (0.45, 95% confidence interval [CI] = 0.26, 0.79) and not among those with cyclin D1- tumors (1.12, 95% CI = 0.67, 1.86). A similar pattern was observed for gastric cardia adenocarcinomas. In contrast, ORs for esophageal squamous cell carcinoma and noncardia gastric adenocarcinomas in relation to NSAID use were reduced, regardless of cyclin D1 status. ORs did not vary with cyclin D1 status in relation to alcohol, body size, or cigarette smoking, with the following exception; for noncardia gastric adenocarcinomas the cyclin D1- tumors showed a 2-fold elevation in the OR with ever smoking. These data suggest that the reduction in risk associated with NSAID use may be restricted to those esophageal and gastric cardia adenocarcinomas that overexpress cyclin D1.
Using FPGA Block-RAM for fast white light interferometry (2017)

White light interferometry is a time consuming operation even on modern architectures. To overcome the high power consumption and size of traditional desktop computers an embedded approach containing the hybrid architecture Zynq will be presented. This architecture contains a dual core ARM and programmable logic provided by an FPGA. FPGAs offer massively parallel logic gates and DSP-slices to parallelise certain tasks. Another important part is the internal memory BRAM. The presented approach aims to speedup calculation time of the ARM processor by utilization of this BRAM. It is well known that memory transfers consume a lot of time. To speed the transfers up, the bottlenecks have to be identified. In this paper it will be illustrated how to easily access an FPGA BRAM from a running operating system and the possible speedup will be analysed and estimated.
A hospital based cross-sectional study to assess various types of non-glaucomatous optic neuropathies (2018)

There is paucity of data on non-glaucomatous optic neuropathy (NGON) from low-and middle-income countries (LMIC). This study was conducted with a purpose to collect a variety of NGON in the adult population.
CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation (2002)

The CC chemokine receptor 3 (CCR3) is expressed by eosinophils, mast cells, and Th2 cells. We used CCR3–/– mice to assess the role of CCR3 in a murine model of allergic skin inflammation induced by repeated epicutaneous sensitization with ovalbumin (OVA), and characterized by eosinophil skin infiltration, local expression of Th2 cytokines, and airway hyperresponsiveness (AHR) to inhaled antigen. Eosinophils and the eosinophil product major basic protein were absent from the skin of sham and OVA-sensitized CCR3–/– mice. Mast cell numbers and expression of IL-4 mRNA were normal in skin of CCR3–/– mice, suggesting that CCR3 is not important for infiltration of the skin by mast cells and Th2 cells. CCR3–/– mice produced normal levels of OVA-specific IgE, and their splenocytes secreted normal amounts of IL-4 and IL-5 following in vitro stimulation with OVA, indicating effective generation of systemic Th2 helper responses. Recruitment of eosinophils to lung parenchyma and bronchoalveolar lavage (BAL) fluid was severely impaired in CCR3–/– mice, which failed to develop AHR to methacholine following antigen inhalation. These results suggest that CCR3 plays an essential role in eosinophil recruitment to the skin and the lung and in the development of AHR.
A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density (2016)

SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its α1 isoform binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95, the principal PSD scaffold, and can occupy as many as 15% of these PDZ domains. We present evidence that synGAP-α1 regulates the composition of the PSD by restricting binding to the PDZ domains of PSD-95. We show that phosphorylation by Ca<sup>2+</sup>/calmodulin-dependent protein kinase II (CaMKII) and Polo-like kinase-2 (PLK2) decreases its affinity for the PDZ domains by several fold, which would free PDZ domains for occupancy by other proteins. Finally, we show that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present in higher concentration in PSDs isolated from mice with a heterozygous deletion of synGAP.
Direct Synthesis of Cycloalkanes from Diols and Secondary Alcohols or Ketones Using a Homogeneous Manganese Catalyst (2019)

A method for the synthesis of substituted cycloalkanes was developed using diols and secondary alcohols or ketones via a cascade hydrogen borrowing sequence. A non-noble and air-stable manganese catalyst (2 mol %) was used to perform this transformation. Various substituted 1,5-pentanediols (3-4 equiv) and substituted secondary alcohols (1 equiv) were investigated to prepare a collection of substituted cyclohexanes in a diastereoselective fashion. Similarly, cyclopentane, cyclohexane, and cycloheptane rings were constructed from substituted 1,4-butanediol, 1,5-pentanediol, and 1,6-hexanediol, and sterically hindered ketones following a (4 + 1), (5 + 1), and (6 + 1) strategy, respectively. This reaction provides an atom economic methodology to construct two C-C bonds at a single carbon center generating high-value cycloalkanes from readily available alcohols as feedstock using an earth-abundant metal catalyst.
BAYWATCH: Robust Beaconing Detection to Identify Infected Hosts in Large-Scale Enterprise Networks (2016)

Sophisticated cyber security threats, such as advanced persistent threats, rely on infecting end points within a targeted security domain and embedding malware. Typically, such malware periodically reaches out to the command and control infrastructures controlled by adversaries. Such callback behavior, called beaconing, is challenging to detect as (a) detection requires long-term temporal analysis of communication patterns at several levels of granularity, (b) malware authors employ various strategies to hide beaconing behavior, and (c) it is also employed by legitimate applications (such as updates checks). In this paper, we develop a comprehensive methodology to identify stealthy beaconing behavior from network traffic observations. We use an 8-step filtering approach to iteratively refine and eliminate legitimate beaconing traffic and pinpoint malicious beaconing cases for in-depth investigation and takedown. We provide a systematic evaluation of our core beaconing detection algorithm and conduct a large-scale evaluation of web proxy data (more than 30 billion events) collected over a 5-month period at a corporate network comprising over 130,000 end-user devices. Our findings indicate that our approach reliably exposes malicious beaconing behavior, which may be overlooked by traditional security mechanisms.
Molecular Determinants of Voltage-dependent Human Ether-a-Go-Go Related Gene (HERG) K+ Channel Block (2002)

The structural determinants for the voltage-dependent block of ion channels are poorly understood. Here we investigate the voltage-dependent block of wild-type and mutant human ether-a-go-go related gene (HERG) K(+) channels by the antimalarial compound chloroquine. The block of wild-type HERG channels expressed in Xenopus oocytes was enhanced as the membrane potential was progressively depolarized. The IC(50) was 8.4 +/- 0.9 microm when assessed during 4-s voltage clamp pulses to 0 mV. Chloroquine also slowed the apparent rate of HERG deactivation, reflecting the inability of drug-bound channels to close. Mutation to alanine of aromatic residues (Tyr-652 or Phe-656) located in the S6 domain of HERG greatly reduced the potency of channel block by chloroquine (IC(50) > 1 mm at 0 mV). However, mutation of Tyr-652 also altered the voltage dependence of the block. In contrast to wild-type HERG, block of Y652A HERG channels was diminished by progressive membrane depolarization, and complete relief from block was observed at +40 mV. HERG channel block was voltage-independent when the hydroxyl group of Tyr-652 was removed by mutating the residue to Phe. Together these findings indicate a critical role for Tyr-652 in voltage-dependent block of HERG channels. Molecular modeling was used to define energy-minimized dockings of chloroquine to the central cavity of HERG. Our experimental findings and modeling suggest that chloroquine preferentially blocks open HERG channels by cation-pi and pi-stacking interactions with Tyr-652 and Phe-656 of multiple subunits.
The reaction of hexamethyldisilazane and subsequent oxidation of trimethylsilyl groups on silica studied by solid-state NMR and FTIR (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe reaction of hexamethyldisilazane and subsequent oxidation of trimethylsilyl groups on silica studied by solid-state NMR and FTIRSuvi Haukka and Andrew RootCite this: J. Phys. Chem. 1994, 98, 6, 1695–1703Publication Date (Print):February 1, 1994Publication History Published online1 May 2002Published inissue 1 February 1994https://pubs.acs.org/doi/10.1021/j100057a025https://doi.org/10.1021/j100057a025research-articleACS PublicationsRequest reuse permissionsArticle Views1586Altmetric-Citations123LEARN 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