gebhart/patrepeval huggingface dataset:
Novel<i>katG</i>mutations causing isoniazid resistance in clinical<i>M. tuberculosis</i>isolates (2015)

We report the discovery and confirmation of 23 novel mutations with previously undocumented role in isoniazid (INH) drug resistance, in catalase-peroxidase (katG) gene of Mycobacterium tuberculosis (Mtb) isolates. With these mutations, a synonymous mutation in fabG1 (g609a), and two canonical mutations, we were able to explain 98% of the phenotypic resistance observed in 366 clinical Mtb isolates collected from four high tuberculosis (TB)-burden countries: India, Moldova, Philippines, and South Africa. We conducted overlapping targeted and whole-genome sequencing for variant discovery in all clinical isolates with a variety of INH-resistant phenotypes. Our analysis showed that just two canonical mutations (katG 315AGC-ACC and inhA promoter-15C-T) identified 89.5% of resistance phenotypes in our collection. Inclusion of the 23 novel mutations reported here, and the previously documented point mutation in fabG1, increased the sensitivity of these mutations as markers of INH resistance to 98%. Only six (2%) of the 332 resistant isolates in our collection did not harbor one or more of these mutations. The third most prevalent substitution, at inhA promoter position -8, present in 39 resistant isolates, was of no diagnostic significance since it always co-occurred with katG 315. 79% of our isolates harboring novel mutations belong to genetic group 1 indicating a higher tendency for this group to go down an uncommon evolutionary path and evade molecular diagnostics. The results of this study contribute to our understanding of the mechanisms of INH resistance in Mtb isolates that lack the canonical mutations and could improve the sensitivity of next generation molecular diagnostics.
Activation of the orphan nuclear receptor RORα counteracts the proliferative effect of fatty acids on prostate cancer cells: Crucial role of 5‐lipoxygenase (2004)

The incidence of prostate carcinoma is very low in Eastern countries, such as Japan, suggesting that life style conditions may play a crucial role in the development of this pathology. Dietary omega-6 polyunsaturated fatty acids, such as linoleic (LA) and arachidonic (AA) acids, have been shown to stimulate the proliferation of prostate cancer cells after being converted into 5-HETE by means of the 5-lipoxygenase (5-LOX) pathway. Blockade of 5-LOX activity has been proposed as an attractive target for the prevention of the mitogenic action of dietary fats on prostate cancer. The 5-LOX gene has been shown to carry a response element for the orphan nuclear receptor RORalpha (for its RORalpha1 isoform in particular) in its promoter region. We attempt to clarify whether activation of RORalpha might modulate the expression of 5-LOX, thus interfering with the mitogenic activity of fatty acids in prostate cancer cells. We show that in androgen-independent DU 145 prostate cancer cells, LA, AA and their metabolite 5-HETE exert a strong stimulatory action on cell proliferation. This effect is completely counteracted by the simultaneous treatment of the cells with a non redox inhibitor of 5-LOX activity. We then demonstrate that: i) RORalpha, and specifically its RORalpha1 isoform, is expressed in DU 145 cells; ii) activation of RORalpha, by means of the thiazolidinedione derivative CGP 52608 (the synthetic RORalpha activator), significantly reduces 5-LOX expression, both at mRNA (as evaluated by comparative RT-PCR) and at protein (as investigated by Western blot analysis) level (this was confirmed by the reduced activity of 5-LOX in CGP 52608 treated cells); and iii) the treatment of DU 145 cells with CGP 52608 completely abrogated the proliferative action of both LA and AA. These results have been confirmed in another androgen-independent prostate cancer cell line (PC3). Our data indicate that, by decreasing the expression of 5-LOX, activation of RORalpha might interfere with the mitogenic activity of fatty acids on prostate cancer. We have shown previously that CGP 52608 reduces the proliferation and the metastatic behavior of DU 145 cells. These observations indicate that the orphan nuclear receptor RORalpha might be considered as a molecular target for the development of new chemopreventive or chemotherapeutic strategies for prostate carcinoma.
Threshold perception performance with computed and screen-film radiography: implications for chest radiography. (1992)

Images of a phantom obtained with computed radiography and standard screen-film imaging were compared to evaluate observer threshold perception performance with a modified contrast-detail technique. Optimum exposure necessary for performance with the imaging plate technique to match that with screen-film techniques was determined, as was comparative performance with variation in kilovoltages, plate type, spatial enhancement, and hard-copy interpolation method. It was found that computed radiography necessitates about 75%-100% more exposure than screen-film radiography to optimally match performance with Ortho-C film with Lanex regular or medium screens (Eastman Kodak, Rochester, NY) for detection of objects 0.05-2.0 cm in diameter. However, only minimal loss of detection performance (approximately 10% overall) was experienced if standard screen-film exposures were used with computed radiography. Little change in observer performance was found with variation in plate type, spatial enhancement, or method of hard-copy interpolation. However, perception performance with computed radiographic images was better at lower kilovoltages.
Synthesis of 6‐phosphatidyl‐L‐ascorbic acid by phospholipase D (1991)

Phospholipase D (EC 3.1.4.4) of Streptomyces species was found to catalyze transphosphatidylation to L-ascorbic acid from phosphatidylcholine (PC) in a biphasic reaction system. The product was identified as 1,2-diacyl-sn-glycero-3-phospho-6'-L-ascorbic acid (PA-AsA) by mass spectrometry and nuclear magnetic resonance spectroscopy. The optimal pH of transphosphatidylation was 4.5 and the rate of PA-AsA formation increased as concentrations of L-ascorbic acid increased. The conversion of PC to PA-AsA was greater than 80%. PA-AsA was found to be more resistant to hydrolysis by phospholipase D than was PC.
Regio‐ and Stereospecific Hydroxylation of Alicyclic Hydrocarbons with Substituted Perbenzoic Acids (1979)

Reactions of the type RH → ROH rarely yield homogeneous products. However, substituted perbenzoic acids transform the cyclic “paraffins” cis-and trans-(1) to (3), X = H, regio- and stereospecifically into the corresponding compounds with X = OH. Acyclic alkanes are likewise oxidizable.
Chitinolytic Microorganisms and Their Possible Application in Environmental Protection (2013)

This paper provides a review of the latest research findings on the applications of microbial chitinases to biological control. Microorganisms producing these enzymes can inhibit the growth of many fungal diseases that pose a serious threat to global crop production. Currently, efforts are being made to discover producers of chitinolytic enzymes. The potential exists that natural biofungicides will replace chemical fungicides or will be used to supplement currently used fungicides, which would reduce the negative impact of chemicals on the environment and support the sustainable development of agriculture and forestry.
The Chief Technology Officer: Strategic Responsibilities and Relationships (2003)

OVERVIEW:The significant role of technology in strategic business decisions has created the need for executives who understand technology and recognize profitable applications to products, services and processes. Many companies have addressed this need through the appointment of a chief technology officer (CTO) whose responsibilities include: monitoring new technologies and assessing their potential to become new products or services; overseeing the selection of research projects to ensure that they have the potential to add value to the company; providing reliable technical assessments of potential mergers and acquisitions; explaining company products and future plans to the trade media; and participating in government, academic and industry groups where there are opportunities to promote the company's reputation and to capture valuable data. Integrating these technology-based activities into the corporate strategy requires that the CTO nurture effective relationships with key people throughout the company. These include the CEO, members of the executive committee, chief scientists, research laboratory directors, and marketing leaders.
Study on a Large-Scale Three-Dimensional Ultrasonic Plastic Welding Vibration System Based on a Quasi-Periodic Phononic Crystal Structure (2020)

The uniformity of amplitude distribution and amplitude gain are two main factors affecting the performance of ultrasonic welding vibration system. In order to improve the uniformity of amplitude distribution and amplitude gain of welding surface to enhance the performance of the vibration system, a new design method of a large-scale three-dimensional ultrasonic plastic welding vibration system based on a quasi-periodic phononic crystal structure is proposed. In this method, the composite horn combined with a conical section and a cylindrical section can effectively improve the output amplitude gain of the welding surface. In addition, the method forms a quasi-periodic phononic crystal structure by slotting in a large-scale three-dimensional tool head, and utilizes the band gap property of the structure to effectively suppress lateral vibration of the tool head and improve the amplitude distribution uniformity of the tool head’s welding surface. However, when the size of the tool head is relatively large, the quasi-periodic phononic crystal structure cannot suppress the lateral vibration very well. Therefore, the paper processes fan-shaped slopes on the output surface of the tool head which can further improve the uniformity of the amplitude distribution and amplitude gain. Finally, the simulation analysis and experiments show that the design method can optimize the large-scale three-dimensional ultrasonic plastic welding system, improve the uniformity of the vibration distribution and increase the output amplitude gain of the welding surface.
Offset pixel aperture technique for extracting depth information (2017)

The 3-dimensional (3D) imaging is an important area which can be applied to face detection, gesture recognition, and 3D reconstruction. Many techniques have been reported for 3D imaging using various methods such as time of fight (TOF), stereo vision, and structured light. These methods have limitations such as use of light source, multi-camera, or complex camera system. In this paper, we propose the offset pixel aperture (OPA) technique which is implemented on a single chip so that the depth can be obtained without increasing hardware cost and adding extra light sources. 3 types of pixels including red (R), blue (B), and white (W) pixels were used for OPA technique. The aperture is located on the W pixel, which does not have a color filter. Depth performance can be increased with a higher sensitivity because we use white (W) pixels for OPA with red (R) and blue (B) pixels for imaging. The RB pixels produce a defocused image with blur, while W pixels produce a focused image. The focused image is used as a reference image to extract the depth information for 3D imaging. This image can be compared with the defocused image from RB pixels. Therefore, depth information can be extracted by comparing defocused image with focused image using the depth from defocus (DFD) method. Previously, we proposed the pixel aperture (PA) technique based on the depth from defocus (DFD). The OPA technique is expected to enable a higher depth resolution and range compared to the PA technique. The pixels with a right OPA and a left OPA are used to generate stereo image with a single chip. The pixel structure was designed and simulated. Optical performances of various offset pixel aperture structures were evaluated using optical simulation with finite-difference time-domain (FDTD) method.
Modelling of Fuel Cell APU Utilisation for Aircraft Applications (2010)

To reduce emissions and increase fuel efficiency, the use fuel cell as an APU has been investigated in aircraft applications. This paper examines when such a system would be advantageous over gas turbine based equipment, in terms of an overall fuel burn saving. It also investigates the impact on fuel consumption with fuel cell APUs installed, including the effect on the engine performance by integrating a fuel cell model with an aircraft network model and a engine driven generator. From this, the impact of fuel cell APUs on the overall fuel efficiency of a flight cycle can be assessed. The study considers the power density of the fuel cells, as the weight of the fuel cell will have a negative impact on fuel consumption. Finding the balance of weight against fuel efficiency is essential to assess the viability of fuel cell APUs. The paper concludes that advances in increasing fuel cell power density may allow fuel cells to be viable as APU replacements. Nomenclature E = Thermodynamic potential (V) E0 = Thermodynamic potential at standard conditions, 1.229 (V) R = Universal gas constant, 8.314 (J/mol.K) T = Absolute temperature (K) N = Number of participating electrons F = Faraday’s constant, 96485.34 (C/mol) a = Activity of species vi = Stochiometric factor of species
Hierarchical image content analysis with an embedded marked point process framework (2014)

In this paper we introduce a probabilistic approach for extracting complex hierarchical object structures from digital images. The proposed framework extends conventional Marked Point Process models by (i) admitting object-subobject ensembles in parent-child relationships and (ii) allowing corresponding objects to form coherent object groups. The proposed method is demonstrated in three application areas: optical circuit inspection, built in area analysis in aerial images, and traffic monitoring on airborne Lidar data.
Performance of a brain PET camera based on anger-logic gadolinium oxyorthosilicate detectors. (2003)

The G-PET scanner attains the goal of high performance for brain imaging through the use of an Anger-logic GSO detector design with continuous optical coupling. This detector design leads to good energy resolution, which is needed in 3D imaging to minimize scatter and random coincidences.
An active radiation shield for cylindrically shaped vehicles (1971)

Covers advancements in spacecraft and tactical and strategic missile systems, including subsystem design and application, mission design and analysis, materials and structures, developments in space sciences, space processing and manufacturing, space operations, and applications of space technologies to other fields.
Boiling water-catalyzed neutral and selective N-Boc deprotection (2009)

A general protocol for removing Boc groups from various types of nitrogen is reported and a preliminary investigation of the reaction mechanism indicates that water acts as a dual acid/base catalyst at elevated temperature.
11 Years of Cyanopyrrolidines as DPP-IV Inhibitors (2007)

Cyanopyrrolidines (cyanopyrrolidides, pyrrolidine-2-nitriles, prolinenitriles) as inhibitors of the serine protease dipeptidyl peptidase IV (DPP-IV, DP IV, CD26, EC 3.4.14.5) were first reported in 1995. The interest in this compound class grew immensely when DPP-IV was discovered as a target for the treatment of type 2 diabetes. The research on cyanopyrrolidines cumulated in the discoveries of vildagliptin (LAF237, NVP-LAF237) and saxagliptin (BMS-477118). These compounds entered Phase III clinical trials in 2004 and 2005, respectively, and an application for market approval has been filed for vildagliptin in 2006. Today cyanopyrrolidines are, as judged by the numbers of patent applications, the most prominent of several series of DPP-IV inhibitors, and have the potential to become valuable medicines for type 2 diabetes in the near future. This review summarizes some historical aspects of the discovery of cyanopyrrolidine DPP-IV inhibitors, and then focuses mainly on structure-activity-relationships, the evolution of different subseries, the possibilities to improve on the chemical instability that is associated with this compound class, and on the discoveries of vildagliptin and saxagliptin. Within this context, the properties of individual compounds and results from biological studies are discussed. The rationale of DPP-IV inhibition, clinical data, and the relevance of selectivity over related proteases are extensively reviewed in other contributions to this issue of Curr. Top. Med. Chem., and are therefore only very briefly touched.
New Models of the Pathophysiology of Schizophrenia: Editors' Introduction (1998)

New models of the pathogenesis of schizophrenia are presented. These models represent hypotheses intended to stimulate discussion and new experimentation. Each of the contributions approach the pathophysiology of schizophrenia from a unique perspective. Yet, all of them emphasize the integration of new advances in basic neuroscience, the functional neuroanatomy of schizophrenia, and information drawn from new biotechnologies, such as neuroimaging and molecular genetics, to provide unique insights into schizophrenia. In each case, the novel hypotheses proposed also illustrate the continuing need for a better understanding of the dynamic interaction between synaptic plasticity and neural circuitry to further our understanding of the human brain in health and disease.
Studies on Chemical Synthesis of Human Cystatin A Gene and Its Expression in Escherichia coli (1989)

A synthetic gene containing the coding sequence for the human cysteine proteinase inhibitor, cystatin A, was obtained by enzymatic assembly of 20 oligodeoxyribonucleotides which had been chemically synthesized by the solid phase phosphoramidite method. It was cloned into an Escherichia coli plasmid. The expression plasmid for cystatin A was constructed by introducing the synthetic gene downstream of the tac promoter of an E. coli plasmid which is a derivative of pKK223-3 with high copy number. The gene was expressed in E. coli JM109 without IPTG-induction. The expression of cystatin A was detected by SDS-polyacrylamide gel electrophoresis of the E. coli JM109 lysate, followed by immunoblotting using rabbit antiserum raised with human epidermal cystatin A and alkaline phosphatase-conjugated goat anti-rabbit IgG. The result showed that the molecular weight of the expression product is identical with that of the authentic protein and the antigenic properties are also the same. Furthermore, the expression product purified with a CM-papain Sepharose affinity column and FPLC system with a Mono-Q column showed the same inhibitory activity for various cysteine proteinases. Also, purified recombinant cystatin A was found to have identical amino acid composition, NH2-terminal amino acid sequence, and peptide-map on reverse phase HPLC with those of the authentic inhibitor.
Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants (2016)

Ketamine, at sub-anesthetic doses, is reported to rapidly decrease depression symptoms in patients with treatment-resistant major depressive disorder (MDD). Many patients do not respond to currently available antidepressants, (for example, serotonin reuptake inhibitors), making ketamine and its enantiomer, esketamine, potentially attractive options for treatment-resistant MDD. Although mechanisms by which ketamine/esketamine may produce antidepressant effects have been hypothesized on the basis of preclinical data, the neurobiological correlates of the rapid therapeutic response observed in patients receiving treatment have not been established. Here we use a pharmacometabolomics approach to map global metabolic effects of these compounds in treatment-refractory MDD patients upon 2 h from infusion with ketamine (n=33) or its S-enantiomer, esketamine (n=20). The effects of esketamine on metabolism were retested in the same subjects following a second exposure administered 4 days later. Two complementary metabolomics platforms were used to provide broad biochemical coverage. In addition, we investigated whether changes in particular metabolites correlated with treatment outcome. Both drugs altered metabolites related to tryptophan metabolism (for example, indole-3-acetate and methionine) and/or the urea cycle (for example, citrulline, arginine and ornithine) at 2 h post infusion (q<0.25). In addition, we observed changes in glutamate and circulating phospholipids that were significantly associated with decreases in depression severity. These data provide new insights into the mechanism underlying the rapid antidepressant effects of ketamine and esketamine, and constitute some of the first detailed metabolomics mapping for these promising therapies.
Distribution, Orientation, and Dynamics of DPH Probes in DPPC Bilayer (2004)

We employ 50 ns molecular dynamics simulations to study the distribution, orientation, and dynamics of 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescent probes in a dipalmitoylphosphatidylcholine (DPPC) bilayer. We find no evidence for clustering of DPH molecules, and our results show that DPH does not prefer to be embedded in the membrane center where free volume is largest. Rather, DPH prefers to be accommodated in the hydrophobic acyl chain region of DPPC, oriented such that the long axis of DPH along its rodlike shape is approximately aligned in the direction of the bilayer normal, thus reflecting the ordering of lipid acyl chains. These conclusions are supported by further studies of radial distribution functions indicating DPH to be located beside the lipid acyl chains. Studies of DPH dynamics in DPPC bilayers reveal a number of rare events, including flip-flops of DPH molecules from one leaflet to another, their rotational diffusion whose time scale can be compared with that found through experiments, and the lateral diffusion of DPH in the plane of the bilayer. For lateral diffusion of DPH, we consider its diffusion mechanism and find that to take place through jumps from one void to another. In all, our results are in favor of using DPH for probing lipid membranes.
<b>Studies of Boron-Nitrogen Compounds. V.<sup>1</sup> Two Isomers of 1,3,5-Trimethylcycloborazane</b> (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies of Boron-Nitrogen Compounds. V.1 Two Isomers of 1,3,5-TrimethylcycloborazaneDonald F. Gaines and Riley. SchaefferCite this: J. Am. Chem. Soc. 1963, 85, 4, 395–397Publication Date (Print):February 1, 1963Publication History Published online1 May 2002Published inissue 1 February 1963https://pubs.acs.org/doi/10.1021/ja00887a006https://doi.org/10.1021/ja00887a006research-articleACS PublicationsRequest reuse permissionsArticle Views130Altmetric-Citations19LEARN 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