gebhart/patrepeval huggingface dataset:
Genetic polymorphisms in the cytochrome P450 2A6 (CYP2A6) gene: implications for interindividual differences in nicotine metabolism. (2001)

During the last couple of years, cytochrome P450 2A6 (CYP2A6; coumarin 7-hydroxylase) has received a lot of attention because it has been shown that it is the principle human nicotine C-oxidase. This enzyme also activates a number of structurally unrelated precarcinogens including many nitrosamines and aflatoxin B1, and metabolizes certain clinically used drugs. There is a pronounced interindividual and interethnic variability in CYP2A6 levels and activity, and much of this can be attributed to polymorphisms in the CYP2A6 gene, where a few inactivating mutations as well as gene deletions have been described. The frequency of the inactive alleles is low in European populations and very few poor metabolizers for the probe drug coumarin have been described in these populations. In contrast, a relatively high allele frequency (15-20%) of the CYP2A6 gene deletion has been found in Asians, resulting in a generally reduced activity in these populations. Because of the importance of CYP2A6 in nicotine metabolism, it has been suggested that the CYP2A6 genotype influences the interindividual differences in smoking behavior as well as lung cancer susceptibility. Several case-control studies have been conducted in this area, but these have yielded conflicting results. The recent progress in the field of CYP2A6 genetics and the development of more specific genotyping methods will facilitate molecular epidemiological studies aimed at clarifying these important issues.
Methylation of the estrogen receptor-α gene promoter is selectively increased in proliferating human aortic smooth muscle cells (2000)

Our data support the concept that the genome of aortic smooth muscle cells is responsive to environmental conditions, and that DNA methylation, in particular methylation of the ERalpha, could contribute to the switch in phenotype observed in these cells.
Global transcriptional responses to the bacteriocin colicin M in Escherichia coli (2013)

At subinhibitory concentrations colicin M induces an adaptive response primarily to protect the bacterial cells against envelope stress provoked by peptidoglycan damage. Among the first induced were genes of the CreBC two-component system known to promote increased resistance against colicins M and E2, providing novel insight into the ecology of colicin M production in natural environments. While an adaptive response was induced nevertheless, colicin M application did not increase biofilm formation, nor induce SOS genes, adverse effects that can be provoked by a number of traditional antibiotics, providing support for colicin M as a promising antimicrobial agent.
Telomerase Reverse Transcriptase Deficiency Prevents Neointima Formation Through Chromatin Silencing of E2F1 Target Genes (2016)

These data indicate a previously unrecognized role for TERT in neointima formation through epigenetic regulation of proliferative gene expression in SMC.
Fluorometric determination of subnanogram levels of nitrite using 5-aminofluorescein (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleFluorometric determination of subnanogram levels of nitrite using 5-aminofluoresceinHerman D. Axelrod and Nancy A. EngelCite this: Anal. Chem. 1975, 47, 6, 922–924Publication Date (Print):May 1, 1975Publication History Published online1 May 2002Published inissue 1 May 1975https://pubs.acs.org/doi/10.1021/ac60356a054https://doi.org/10.1021/ac60356a054research-articleACS PublicationsRequest reuse permissionsArticle Views336Altmetric-Citations57LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Improving vulnerability remediation through better exploit prediction (2020)

Abstract Despite significant innovations in IT security products and research over the past 20 years, the information security field is still immature and struggling. Practitioners lack the ability to properly assess cyber risk, and decision-makers continue to be paralyzed by vulnerability scanners that overload their staff with mountains of scan results. In order to cope, firms prioritize vulnerability remediation using crude heuristics and limited data, though they are still too often breached by known vulnerabilities for which patches have existed for months or years. And so, the key challenge firms face is trying to identify a remediation strategy that best balances two competing forces. On one hand, it could attempt to patch all vulnerabilities on its network. While this would provide the greatest ‘coverage’ of vulnerabilities patched, it would inefficiently consume resources by fixing low-risk vulnerabilities. On the other hand, patching a few high-risk vulnerabilities would be highly ‘efficient’, but may leave the firm exposed to many other high-risk vulnerabilities. Using a large collection of multiple datasets together with machine learning techniques, we construct a series of vulnerability remediation strategies and compare how each perform in regard to trading off coverage and efficiency. We expand and improve upon the small body of literature that uses predictions of ‘published exploits’, by instead using ‘exploits in the wild’ as our outcome variable. We implement the machine learning models by classifying vulnerabilities according to high- and low-risk, where we consider high-risk vulnerabilities to be those that have been exploited in actual firm networks.
The Stickizer: a layout to symbolic converter (2003)

The Stickizer, a tool for conversion from layout to symbolic, is presented. Thinning, a method borrowed from mathematical morphology is used to achieve Stickizing of polygons. Stickizer's main features are applicability to Manhattan-geometry and 45 degrees -geometry layouts, extraction of transistors of any shape, strict symbolic/layout equivalence for Manhattan-geometry cells (reversibility of the translation), adaptation of 45 degrees -geometry cells to Manhattan compactors, independence from the technology, hierarchy handling with minimal user intervention, adaptability to a wide range of layout formats and design conventions, and reasonable execution time. It has been used on over 300 cells with sizes up to 6000 transistors and 2 Mbit.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Taking whispering gallery-mode single virus detection and sizing to the limit (2012)

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 V. R. Dantham, S. Holler, V. Kolchenko, Z. Wan, S. Arnold; Taking whispering gallery-mode single virus detection and sizing to the limit. Appl. Phys. Lett. 23 July 2012; 101 (4): 043704. https://doi.org/10.1063/1.4739473 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 ContentAIP Publishing PortfolioApplied Physics Letters Search Advanced Search |Citation Search
Characterization of Nanoparticle Dispersion in Red Blood Cell Suspension by the Lattice Boltzmann-Immersed Boundary Method (2016)

Nanodrug-carrier delivery in the blood stream is strongly influenced by nanoparticle (NP) dispersion. This paper presents a numerical study on NP transport and dispersion in red blood cell (RBC) suspensions under shear and channel flow conditions, utilizing an immersed boundary fluid-structure interaction model with a lattice Boltzmann fluid solver, an elastic cell membrane model and a particle motion model driven by both hydrodynamic loading and Brownian dynamics. The model can capture the multiphase features of the blood flow. Simulations were performed to obtain an empirical formula to predict NP dispersion rate for a range of shear rates and cell concentrations. NP dispersion rate predictions from the formula were then compared to observations from previous experimental and numerical studies. The proposed formula is shown to accurately predict the NP dispersion rate. The simulation results also confirm previous findings that the NP dispersion rate is strongly influenced by local disturbances in the flow due to RBC motion and deformation. The proposed formula provides an efficient method for estimating the NP dispersion rate in modeling NP transport in large-scale vascular networks without explicit RBC and NP models.
Updates in the Clinical Development of Epacadostat and Other Indoleamine 2,3-Dioxygenase 1 Inhibitors (IDO1) for Human Cancers (2018)

Recent application of immunotherapy in clinical oncology revolutionized our management of advanced human cancers. Check point inhibitors targeting CTLA4 and PD-1/PD-L1 axis are immunotherapeutic agents currently available to treat a variety of cancers. However, a novel therapeutic approach is needed to further improve patient outcome with these agents. Indoleamine 2,3-dioxygenase 1 (IDO1) is a rate-limiting enzyme in the metabolism of essential amino acid tryptophan in the peripheral tissue. IDO1 is overexpressed in human cancer cells and suppresses effector T cell function and promotes regulatory T cells (Tregs). Overexpression of IDO1 is associated with poor patient survival in several types of human cancer. These findings indicate that IDO1 is a promising target that can improve the treatment outcome in the field of Immuno-oncology. Several orally available IDO1 inhibitors including Epacadostat have entered human clinical trials over the last few years without a major safety concern. Although there is no objective response in single-agent trials, combination regimens with PD-1 inhibitors appear to exceed the activity of PD-1 inhibitors alone. Recent phase III ECHO 301 trial testing the combination of Epacadostat with Pembrolizumab in melanoma did not show superior outcome compared to Pembrolizumab alone. This lead to halting of other phase III trials using IDO1 inhibitors. In this minireview, we will discuss the recent clinical development of Epacadostat and other IDO1 inhibitors.
Piperidine Derivatives. XVII. Local Anesthetics Derived from Substituted Piperidinoalcohols (1946)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPiperidine Derivatives. XVII. Local Anesthetics Derived from Substituted PiperidinoalcoholsS. M. McElvain and Thomas P. CarneyCite this: J. Am. Chem. Soc. 1946, 68, 12, 2592–2600Publication Date (Print):December 1, 1946Publication History Published online1 May 2002Published inissue 1 December 1946https://pubs.acs.org/doi/10.1021/ja01216a051https://doi.org/10.1021/ja01216a051research-articleACS PublicationsRequest reuse permissionsArticle Views720Altmetric-Citations39LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Imaging of the active <i>B<sub>1</sub></i> field <i>in vivo</i> (1996)

The authors describe a method for accurate in vivo multislice imaging of the active component of the B1 field which is based on a previously proposed method, which uses the signal intensity ratio of two images measured with different excitation angles, and a repetition time TR 5 > or = 5 T1. The new method essentially reduces repetition and scan time by means of an additional compensating pulse. The suppression of T1 effects by this pulse are verified with simulations and measurements. Further investigations concerned the influence of slice selective excitation and magnetization transfer in multislice imaging to the B1 field determination. The stability and accuracy of the presented method is shown by several phantom and in vivo measurements. With the described method the active B1 field can be determined in vivo in 23 cross-sections in less than 6 min.
Soluble Thrombomodulin Antigen in Conditioned Medium Is Increased by Damage of Endothelial Cells (1991)

Thrombomodulin (TM) exists not only in endothelial cells but also in circulating plasma as soluble heterogeneous fragments. A release mechanism of soluble TM antigen from endothelial cells was investigated. Cultured human umbilical vein endothelial cells released about 0.6% of total cellular TM antigen into conditioned medium during 24 h. The release of TM antigen was not influenced by addition of various concentrations (0.01-5.0 microM) of monensin, which inhibits intracellular transport of secretory proteins, though the secretion of plasminogen activator inhibitor-1 from the cells was inhibited. The release of TM antigen was not increased when total cellular TM level increased 1.3- or 1.4-fold relative to control cells after stimulation with 0.1-1.0 U/ml thrombin or 3 mM dibutyryl cAMP, respectively. Exposure of endothelial cells for 6 h to mixture of 1 microM N-formyl-methionyl-leucyl-phenylalanine (FMLP) and 100 ng/ml lipopolysaccharide (LPS) decreased cellular TM level by 30% relative to control cells without increase in the TM release. The FMLP and LPS-stimulated leukocyte treatment of the cells increased the release of TM antigens into the medium in a time-dependent manner and the increased release of TM antigen paralleled the extent of cell damage as measured by 51Cr release. Hydrogen peroxide treatment of the cells increased the release of TM antigens into the medium in a time- and concentration-dependent manner. The increased release of TM antigen by hydrogen peroxide also paralleled the extent of cell damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Bis(1,3-di-<i>tert</i>-butylimidazolin-2-iminato) Titanium Complexes as Effective Catalysts for the Monodisperse Polymerization of Propylene (2012)

The use of bis(1,3-di-tert-butylimidazolin-2-iminato) titanium dichloride (1) and dimethyl (2) complexes in the polymerization of propylene is presented. The complexes were activated using different amounts of methylalumoxane (MAO), giving in each case a very active catalytic mixture and producing polymers with a narrow molecular weight distribution (polydispersity = 1.10). The use of the cocatalyst triphenylcarbenium (trityl) tetra(pentafluorophenyl)borate totally inhibits the reaction, producing the corresponding bis(1,3-di-tert-butylimidazolin-2-iminato) titanium(III) methyl complex, the trityl radical ((•)CPh(3)), the anionic MeB(C(6)F(5))(4)(-), B(C(6)F(5))(3), and the bis(1,3-di-tert-butylimidazolin-2-iminato) titanium(IV) dimethyl·B(C(6)F(5))(3) complex. The use of a combination of physical methods such as NMR, ESR-C(60), and MALDI-TOF analyses enabled us to propose a plausible mechanism for the polymerization of propylene, presenting that the polymerization is mainly carried out in a living fashion. In addition, we present a slow equilibrium toward a small amount of a dormant species responsible for 2,1-misinsertions and chain transfer processes.
Inhibition of Follicle-Stimulating Hormone Receptor Binding by CirculatingImmunoglobulins* (1982)

We have characterized a circulating inhibitor of FSH receptor binding found in two patients with hypergonadotropic amenorrhea and myasthenia gravis. The inhibitor behaves as an immunoglobulin according to several criteria, including precipitation by 30% ammonium sulfate, migration on DEAE-cellulose chromatography, specific binding to protein A-Sepharose, characterization as a 7S protein in sucrose density gradients, and immunoprecipitation with specific antihuman immunoglobulin G. Evidence suggests that these antibodies are directed at determinants on or near the FSH receptor, and they may be responsible for the observed clinical FSH resistance.
Tau Aggregation and Toxicity in a Cell Culture Model of Tauopathy (2007)

Intracellular aggregation of the microtubule-associated protein tau into filamentous inclusions is a defining characteristic of Alzheimer disease. Because appearance of tau-aggregate bearing lesions correlates with both cognitive decline and neurodegeneration, it has been hypothesized that tau aggregation may be directly toxic to cells that harbor them. Testing this hypothesis in cell culture has been complicated by the resistance of full-length tau isoforms to aggregation over experimentally tractable time periods. To overcome this limitation, a small-molecule agonist of the tau aggregation reaction, Congo red, was used to drive aggregation within HEK-293 cells expressing full-length tau isoform htau40. Formation of detergent-insoluble aggregates was both time and agonist concentration dependent. At 10 microM Congo red, detergent-insoluble aggregates appeared with pseudo-first order kinetics and a half-life of approximately 5 days. By 7 days in culture, total tau levels increased 2-fold, with approximately 30% of total tau converted into detergent-insoluble aggregates. Agonist addition also led to rapid losses in the tubulin binding activity of tau, although tau was not hyperphosphorylated as judged by occupancy of phosphorylation sites Ser396/Ser404. Tau aggregation was associated with decreased viability as detected by ToPro-3 uptake. The results, which establish a new approach for analysis of tau aggregation in cells independent of tau hyperphosphorylation, suggest that conformational changes associated with aggregation are incompatible with microtubule binding, and that toxicity associated with intracellular tau aggregation is not acute but develops over a period of days.
A DC-isolated gate drive IC with drive-by-microwave technology for power switching devices (2012)

Outstanding GaN-based HFETs (HFET: Heterojunction Field-Effect Transistors) [1] power devices are expected to replace all Si power devices in high power applications such as inverter systems due to their excellent performance. In order to exploit the full potential of such emerging GaN power devices, the gate driver that controls the device by a pulse width modulation (PWM) signal is becoming more important. The vital function of the gate driver is to provide an isolated gate signal against the reference source voltage that operates at high voltage. In addition to this function, their integration with GaN power HFETs is also desirable to achieve smaller system size, lower cost and user-friendliness. Although there are several signal isolation techniques for a gate driver such as to use a photo-coupler and wireless pulse transformer [2], these techniques have disadvantages such as large system size and difficulty in integration. Other bootstrap or charge pump techniques [3] in high voltage gate drivers (HVIC) have been developed to generate a reference voltage, but the driver can only be used in particular applications such as inverters. Meanwhile, we have focused our attention on the recent technology of wireless power transmission using an electromagnetic resonant coupler (EMRC) [4] with an open-ring resonator [5], which is very attractive due to its high efficiency in power transmission and its compactness at high frequency.
Rapid and Sensitive Spectrophotometry. II. A Stopped-Flow Attachment for a Stabilized Quartz Spectrophotometer (1951)

The stabilization of the light sources and the photocell circuits of a quartz spectrophotometer and the design of suitable stopped flow apparatuses are described. The latter have been designed for 1.6- and 10-mm optical paths and have been shown to give rapid mixing (&lt;0.1 sec). Errors of optical density measurement are diminished by rectangular observation tubes, and errors of extinction coefficients are minimized by a narrow spectral interval (less than 2 mμ from 230–600 mμ). The error of optical density caused by the photoelectric circuits is about 1×10−4 for a response time (10–90 percent) of 1 sec. The application of this apparatus to the measurement of rapid chemical reactions in the visible and ultraviolet regions is described.
Virulence factors in<i>Escherichia coli</i>isolated from calves with diarrhea in Vietnam (2011)

This study was conducted to determine the prevalence and characteristics of pathogenic Escherichia (E.) coli strains from diarrheic calves in Vietnam. A total of 345 E. coli isolates obtained from 322 diarrheic calves were subjected to PCR and multiplex PCR for detection of the f5, f41, f17, eae, sta, lt, stx1, and stx2 genes. Of the 345 isolates, 108 (31.3%) carried at least one fimbrial gene. Of these 108 isolates, 50 carried genes for Shiga toxin and one possessed genes for both enterotoxin and Shiga toxin. The eae gene was found in 34 isolates (9.8%), 23 of which also carried stx genes. The Shiga toxin genes were detected in 177 isolates (51.3%) and the number of strains that carried stx1, stx2 and stx1/stx2 were 46, 73 and 58, respectively. Among 177 Shiga toxin-producing E. coli isolates, 89 carried the ehxA gene and 87 possessed the saa gene. Further characterization of the stx subtypes showed that among 104 stx1-positive isolates, 58 were the stx1c variant and 46 were the stx1 variant. Of the 131 stx2-positive strains, 48 were stx2, 48 were stx2c, 11 were stx2d, 17 were stx2g, and seven were stx2c/stx2g subtypes. The serogroups most prevalent among the 345 isolates were O15, O20, O103 and O157.
A persistent level of Cisd2 extends healthy lifespan and delays aging in mice (2012)

The CISD2 gene, which is an evolutionarily conserved novel gene, encodes a transmembrane protein primarily associated with the mitochondrial outer membrane. Significantly, the CISD2 gene is located within the candidate region on chromosome 4q where a genetic component for human longevity has been mapped. Previously, we have shown that Cisd2 deficiency shortens lifespan resulting in premature aging in mice. Additionally, an age-dependent decrease in Cisd2 expression has been detected during normal aging. In this study, we demonstrate that a persistent level of Cisd2 achieved by transgenic expression in mice extends their median and maximum lifespan without any apparent deleterious side effects. Cisd2 also ameliorates age-associated degeneration of the skin, skeletal muscles and neurons. Moreover, Cisd2 protects mitochondria from age-associated damage and functional decline as well as attenuating the age-associated reduction in whole-body energy metabolism. These results suggest that Cisd2 is a fundamentally important regulator of lifespan and provide an experimental basis for exploring the candidacy of CISD2 in human longevity.