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Identification of arylamine N-acetyltransferase inhibitors as an approach towards novel anti-tuberculars

Protein & Cell 2010年第1期1卷 82-95页

作者： Isaac M.Westwood Sanjib Bhakta Angela J.Russell Elizabeth Fullam Matthew C.Anderton Akane Kawamura Andrew W.Mulvaney Richard J.Vickers Veemal Bhowruth gurdyal S.Besra Ajit Lalvani stephen g.davies Edith Sim Department of Pharmacology University of OxfordOxford OX13QTUnited Kingdom Chemistry Research Laboratory Department of Organic ChemistryUniversity of OxfordOxford OX13QLUnited Kingdom School of Biosciences University of BirminghamEdgbastonBirmingham B152TTUnited Kingdom Tuberculosis Immunology group Department of Respiratory MedicineNational Heart and Lung InstituteWright Fleming Institute of Infection and ImmunityImperial College LondonNorfolk PlaceLondon W21PGUnited Kingdom Structure-Based Drug Design Team Sections of Structural Biology and Cancer TherapeuticsInstitute of Cancer ResearchChester Beatty LaboratoriesLondon SW36JBUnited Kingdom Institute of Structural and Molecular Biology Department of Biological ScienceBirkbeckUniversity of LondonLondon WC1E 7HXUnited Kingdom

New anti-tubercular drugs and drug targets are urgently needed to reduce the time for treatment and also to identify agents that will be effective against Mycobacterium tuberculosis persisting *** have a unique cell *** of the gene for arylamine N-acetyltransferase(NAT)decreases mycobacterial cell wall lipids,particularly the distinctive mycolates,and also increases antibiotic susceptibility and killing within macrophage of Mycobacterium bovis *** nat gene and its associated gene cluster are almost identical in sequence in *** BCg and *** gene cluster is essential for intracellular survival of *** have therefore used pure NAT protein for high-throughput screening to identify several classes of small molecules that inhibit NAT ***,we characterize one class of such molecules—triazoles—in relation to its effects on the target enzyme and on both *** BCg and *** most potent triazole mimics the effects of deletion of the nat gene on growth,lipid disruption and intracellular *** also present the structure-activity relationship between NAT inhibition and effects on mycobacterial growth,and use ligand-protein analysis to give further insight into the structure-activity *** conclude that screening a chemical library with NAT protein yields compounds that have high potential as anti-tubercular agents and that the inhibitors will allow further exploration of the biochemical pathway in which NAT is involved.

关键词： N-acetyltransferase Mycobacterium tuberculosis triazoles screening

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Modeling mitochondria,where are the numbers?

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Neural Regeneration Research 2024年第7期19卷 1435-1436页

作者： Adrian M.davies Alan g.Holt University Center Shrewsbury ShrewsburyShropshireUK

Models and simulations are particularly useful for exploring ideas and concepts in the biological sciences that are expe rimentally *** silico methods are also gaining acceptance with regulatory authorities as an alte... 详细信息

关键词： eliminate authorities acceptance

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Applications of cnoidal and snoidal wave solutions via optimal system of subalgebras for a generalized extended (2+1)-D quantum Zakharov-Kuznetsov equation with power-law nonlinearity in oceanography and ocean engineering

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Journal of Ocean Engineering and Science 2024年第2期9卷 126-153页

作者： Oke davies Adeyemo International Institute for Symmetry Analysis and Mathematical Modelling Department of Mathematical SciencesNorth-West UniversityMafikeng CampusPrivate Bag X 2046Mmabatho 2735Republic of South Africa

The nonlinear evolution equations have a wide range of applications,more precisely in physics,biology,chemistry and engineering *** domain serves as a point of interest to a large extent in the world’s mathematical ***,this paper purveys an analytical study of a generalized extended(2+1)-dimensional quantum Zakharov-Kuznetsov equation with power-law nonlinearity in oceanography and ocean *** Lie group theory of differential equations is utilized to compute an optimal system of one dimension for the Lie algebra of the *** further reduce the equation using the subalgebras ***,more general solutions of the underlying equation are secured for some special cases of n with the use of extended Jacobi function expansion ***,we secure new bounded and unbounded solutions of interest for the equation in various solitonic structures including bright,dark,periodic(cnoidal and snoidal),compact-type as well as singular *** applications of cnoidal and snoidal waves of the model in oceanography and ocean engineering for the first time,are outlined with suitable *** can be of interest to oceanographers and ocean engineers for future ***,to visualize the dynamics of the results found,we present the graphic display of each of the ***,we construct conservation laws of the understudy equation via the application of Noether’s theorem.

关键词： A generalized extended(2+1)-dimensional quantum Zakharov-Kuznetsov equation Lie point symmetries Optimal system of subalgebras Cnoidal and snoidal waves Extended Jacobi function expansion technique Conservation laws

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LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu Elizabeth R.davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben g.Marshall David Hancock Tim Wallis Julian Downward Rob M.Ewing Donna E.davies Mark g.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a *** IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39L Crosstalk EMT LKB1 Pulmonary fibrosis

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Developing a new agenda for increased food and climate security

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Frontiers of Agricultural Science and Engineering 2024年第1期11卷 35-54页

作者： William J.davies Lancaster Environment Centre Lancaster UniversityLancasterLA14YQUK

In many countries, political and environmental pressures are currently combining to generate a perfect storm of circumstances that is reducing food availability, increasing food costs and thereby reducing the availability of food to many. The UK is currently considering new national food and land management policies, and attention is also being given to legislation to address diet-related health issues. Many now argue for a revolution in UK farming practices to reduce their impact on the natural environment. The UK is not alone in facing these and other challenges. Both the contribution of agriculture to greenhouse gas(gHg) emissions and the effects of climate change on food production are issues receiving worldwide *** agricultural practices can result in greater C capture, reduced gHg emissions, enhanced soil quality and enhanced biodiversity. However, it is questioned if such farming systems will be productive enough to feed a growing population with the food required for social and health benefits. To fully exploit the impact of new plant science in farmer fields, it is imperative to effectively link science to farming practices and conduct a broader conversation around the food revolution with social scientists and with the general public.

关键词： Climate resilience food security human health planetary health regenerative agriculture

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DEM investigation of strength and critical state behaviours of granular materials under true triaxial loadings

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Particuology 2024年第2期85卷 198-212页

作者： Minyi Zhu guobin gong Jun Xia stephen Wilkinson Department of Civil Engineering Xi'an Jiaotong-Liverpool UniversityChina Department of Civil Engineering and Industrial Design University of LiverpoolLiverpoolUK Faculty of Engineering and Information Sciences University of Wollongong in DubaiUnited Arab Emirates

This paper investigates the strength and critical state(CS)behaviours of granular materials via DEM simulations of true triaxial drained tests under three different loading modes including constant b(in-termediate stress ratio)tests with constantσ'1(major principal stress),constant p(mean pressure)and constantσ'3(minor principal stress)*** this end,a series of samples are generated with the same particle size distribution,and with the confining stresses ranging from 100 kPa to 900 *** CS is achieved for all *** the macroscopic behaviours and the microscopic behaviours are examined and compared considering different loading modes,confining stresses and intermediate stress ratios(b).The critical state lines(CSLs)are found to be unique and independent of the loading modes,but dependent on the b *** CSLs with b=0 and b=1 form the two boundaries of CSLs respectively beyond which CSLs under all other b tests cannot go *** different strength criteria are examined and compared in terms of both peak and CS *** Mohr-Coulomb strength criterion is found to be only suitable for axisymmetric loading *** Lade-Duncan criterion is only suitable for describing peak strengths,which is dependent on the loading modes and confining *** Satake criterion and Matsuoka-Nakai criterion are the more appropriate strength criteria for describing CS failures,indicating that the CS values of both the Satake parameter and the Matsuoka-Nakai parameter describe an inherent property that characterizes the CS failure for a given type of *** CS mechanical coordination number is fitted by a curved line for a given b value,which is unique regardless of the loading *** peak and CS values of both major and minor principal fabric tensors decrease with increasing b values,while they increase with increasing b values for the intermediate principal fabric tensor.

关键词： Discrete element method Intermediate stress ratio Dilation Critical state Failure criterion

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Non-canonical BRAF variants and rearrangements in hairy cell leukemia

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Oncology Research 2024年第9期32卷 1423-1427页

作者： stephen E.LANgABEER Cancer Molecular Diagnostics St.James’s HospitalDublinD08 W9RTIreland

Hairy cell leukemia(HCL)is an uncommon mature B-cell malignancy characterized by a typical morphology,immunophenotype,and clinical *** vast majority of HCL patients harbor the canonical BRAF V600E mutation which has become a rationalized target of the subsequently deregulated RAS-RAF-MEK-MAPK signaling pathway in HCL patients who have relapsed or who are refractory to front-line ***,several HCL patients with a classical phenotype display non-canonical BRAF mutations or *** include sequence variants within alternative exons and an oncogenic fusion with the IgH *** must be taken in the molecular diagnostic work-up of patients with typical HCL but without the BRAF V600E to include investigation of these uncommon ***,functional characterization,and reporting of further such patients is likely to provide insights into the pathogenesis of HCL and enable rational selection of targeted inhibitors in such patients if required.

关键词： Hairy cell leukemia BRAF Molecular diagnostics Targeted therapy

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DCFNet:Discriminant Correlation Filters Network for Visual Tracking

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Journal of Computer Science & Technology 2024年第3期39卷 691-714页

作者：胡卫明王强高晋李兵 stephen Maybank State Key Laboratory of Multimodal Artificial Intelligence Systems Institute of AutomationChinese Academy of Sciences Beijing 100190China Department of Computer Science and Information Systems Birkbeck CollegeLondon WC1E 7HXU.K.

CNN(convolutional neural network)based real time trackers usually do not carry out online network update in order to maintain rapid tracking *** inevitably influences the adaptability to changes in object *** filter based trackers can update the model parameters online in real *** this paper,we present an end-to-end lightweight network architecture,namely Discriminant Correlation Filter Network(DCFNet).A differentiable DCF(discriminant correlation filter)layer is incorporated into a Siamese network architecture in order to learn the convolutional features and the correlation filter *** correlation filter can be efficiently updated *** previous work,we introduced a joint scale-position space to the DCFNet,forming a scale DCFNet which carries out the predictions of object scale and position *** combine the scale DCFNet with the convolutional-deconvolutional network,learning both the high-level embedding space representations and the low-level fine-grained representations for *** adaptability of the fine-grained correlation analysis and the generalization capability of the semantic embedding are complementary for visual *** back-propagation is derived in the Fourier frequency domain throughout the entire work,preserving the efficiency of the *** evaluations on the OTB(Object Tracking Benchmark)and VOT(Visual Object Tracking Challenge)datasets demonstrate that the proposed trackers have fast speeds,while maintaining tracking accuracy.

关键词： correlation filter convolutional neural network(CNN) visual tracking

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Data Temperature Informed Streaming for Optimising Large-Scale Multi-Tiered Storage

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Big Data Mining and Analytics 2024年第2期7卷 371-398页

作者： Dominic davies-Tagg Ashiq Anjum Ali Zahir Lu Liu Muhammad Usman Yaseen Nick Antonopoulos Department of Computing University of DerbyDerbyDE221GBUK Department of Informatics University of LeicesterLeicesterLE17RHUK Department of Computer Science COMSATS University IslamabadIslamabad 45550Pakistan Edinburgh Napier University EdinburghEH114BNUK

Data temperature is a response to the ever-growing amount of *** data have to be stored,but they have been observed that only a small portion of the data are accessed more frequently at any one *** leads to the concept of hot and cold *** data can be migrated away from high-performance nodes to free up performance for higher priority *** studies classify hot and cold data primarily on the basis of data age and usage *** present this as a limitation in the current implementation of data *** is due to the fact that age automatically assumes that all new data have priority and that usage is purely *** propose new variables and conditions that influence smarter decision-making on what are hot or cold data and allow greater user control over data location and their *** identify new metadata variables and user-defined variables to extend the current data temperature *** further establish rules and conditions for limiting unnecessary movement of the data,which helps to prevent wasted input output(I/O)*** also propose a hybrid algorithm that combines existing variables and new variables and conditions into a single data *** proposed system provides higher accuracy,increases performance,and gives greater user control for optimal positioning of data within multi-tiered storage solutions.

关键词： data temperature hot and cold data multi-tiered storage metadata variable multi-temperature system

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Role of intravascular ultrasound and optical coherence tomography in intracoronary imaging for coronary artery disease:a systematic review

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Journal of geriatric Cardiology 2024年第1期21卷 104-129页

作者： Maruf Sarwar stephen Adedokun Mahesh Anantha Narayanan Department of Cardiovascular Sciences White River HealthBatesvilleARUSA Division of Cardiology University of Tennessee at MemphisTNUSA University of Arkansas Medical Sciences Little RockARUSA

Coronary angiography has long been the standard for coronary imaging,but it has limitations in assessing vessel wall anatomy and guiding percutaneous coronary intervention(PCI).Intracoronary imaging techniques like intravascular ultrasound(IVUS)and optical coherence tomography(OCT)can overcome these *** uses ultrasound and OCT uses near-infrared light to visualize coronary pathology in unique ways due to differences in temporal and spatial *** techniques have evolved to offer clinical utility in plaque characterization and vessel assessment during ***-analyses and adjusted observational studies suggest that both IVUS and OCT-guided PCI correlate with reduced cardiovascular risks compared to angiographic guidance *** IVUS demonstrates consistent clinical outcome benefits,OCT evidence is less *** has progressed from early motion detection to high-resolution systems,with smaller compatible *** utilizes near infrared light to achieve unparalleled resolutions,but requires temporary blood clearance for optimal *** visualization and guidance make IVUS and OCT well-suited for higher risk PCI in patients with diabetes and chronic kidney disease by allowing detailed visualization of complex lesions and ensuring optimal stent deployment and positioning in PCI for patients with type 2 diabetes and chronic kidney disease,improving *** and recent advancements in zero-and low-contrast OCT techniques can reduce nephrotoxic contrast exposure,thus helping to minimize PCI complications in these high-risk patient *** and OCT provide valuable insights into coronary pathophysiology and guide interventions precisely compared to angiography *** have comparable clinical outcomes,emphasizing the need for tailored imaging choices based on clinical *** refinement and integration of intravascular imaging will likely play a pivotal role in optimizing coronary interventions and outcomes.

关键词： coronary anatomy limitations

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