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The ubiquitin ligase Siah2 is revealed as an accomplice of the androgen receptor in castration resistant prostate cancer

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Asian Journal of Andrology 2013年第4期15卷 447-448页

作者： michael R Freeman Research Division of Cancer Biology and Therapeutics Departments of Surgery Medicine and BiomedicalSciences Cancer Biology Program Samuel OschinComprehensive Cancer Institute Los Angeles CA90048 USA

The androgen receptor （AR） remains the primary molecular target forprostate cancer （PCa） treatment and for development of novel therapies. Profiling and other analyses of human prostate adenocarcinoma have shown that the AR is still functional during latestage disease in the absence of circulating hormone fol lowing castration therapy. The molecular mechanisms that operate during this ＇cas tration resistant＇ phase are still not well understood. Qi et al. have now implicated the ubiquitin ligase Siah2 as an important mediator of AR action in castration resis tant prostate cancer （CRPC）. Siah2 was found to target repressed AR chromatin complexes for degradation, resulting in activation of ARregulated genes involved in tumor cell proliferation, cell motility and lipid metabolism. The authors show a requirement for Siah2 activity for PCa cell growth under conditions of low androgen, and also that targeting Siah2 results in tumor growth suppression under castrate conditions. These findings identify a new mechanism of AR regulation in progressing disease as well as a novel enzymatic target for therapeutic intervention. The AR is a wellstudied hormone receptor that belongs to the large nuclear receptor gene superfamily. AR is activated by androgen binding （principally 5：~dihydrotestosterone, 5DHT）, which elicits changes in AR resident cytosolic complexes, translocation of the receptor to cell nuclei, formation of multiprotein transcriptional complexes onchromatin, and activation or repression of gene expression. Experiments with in vivo model systems have provided evidence that virtually all physiologic processes affected by androgens require the AR as a mediator of molecular effects at the gene level.1 AR is widely expressed beyond the reproductive systems and is believed to play important roles in several nonreproductive tissues, including muscle and brain. The fact that PCa growth is initially dependent on the pre sence of androgens in the circulation, and that prostat

关键词： ligase revealed accomplice

Two-dimensional near-infrared photonic crystal fabrication by generation of void channels in solid resin

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Chinese Optics Letters 2003年第12期1卷 719-721页

作者： michael James Ventura Centre for Micro-Phtonics and the Centre for Ultrahigh-Highwidth Devices for Optical Systems School of Biophysical Sciences and Electrical Engineering Swinburne University of Technology PO Box 218 Hawthorn Victoria 3122 Australia

Two-dimensional (2D) triangular void channel photonic crystals with different lattice constants stacked in two different directions were fabricated by using femtosecond laser micro-explosion in solid polymer material. Fundamental and higher-order stop gaps were observed both in the infrared transmission and reflection spectra. There is an approximately linear relationship between the gap position and the lattice constant. The suppression of the fundamental gap is as high as 70% for 24-layer structures stacked in the T-M direction.

关键词： of as Two-dimensional near-infrared photonic crystal fabrication by generation of void channels in solid resin by that were for with

Pico-washing:simultaneous liquid addition and removal for continuous-flow washing of microdroplets

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Microsystems & Nanoengineering 2022年第2期8卷 249-261页

作者： michael J.Siedlik David Issadore Department of Bioengineering University of PennsylvaniaPhiladelphiaPA 19104United States

Droplet microfluidics is based on a toolbox of several established unit operations,including droplet generation,incubation,mixing,pico-injection,and *** the last two decades,the development of droplet microfluidic systems,which incorporate these multiple unit operations into a workflow,has demonstrated unique capabilities in fields ranging from single-cell transcriptomic analyses to materials *** unit operation that is sorely underdeveloped in droplet microfluidics is washing,exchange of the fluid in a droplet with a different ***,we demonstrate what we name the"pico-washer,"a unit operation capable of simultaneously adding fluid to and removing fluid from droplets in flow while requiring only a small footprint on a microfluidic *** describe the fabrication strategy,device architecture,and process parameters required for stable operation of this technology,which is capable of operating with kHz droplet ***,we provide an image processing workflow to characterize the washing process with microsecond and micrometer ***,we demonstrate the potential for integrated droplet workflows by arranging two of these unit operations in series with a droplet generator,describe a design rule for stable operation of the pico-washer when integrated into a system,and validate this design rule *** anticipate that this technology will contribute to continued development of the droplet microfluidics toolbox and the realization of novel droplet-based,multistep biological and chemical assays.

关键词： operations simultaneous removing

Ricochet quantification using a multiple sensor approach

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Defence Technology（防务技术） 2021年第2期17卷 305-314页

作者： michael Muster Amer Hameed David Wood Centre for Defence Engineering Cranfield UniversityDefence Academy of the United KingdomShrivenhamSN68LAUK

This study investigates the ricochet behaviour of three different small-arms projectile types using a novel ricochet measuring *** results can be used to estimate the danger potential of ricochets on shooting ranges.A ricochet is the change of direction and velocity of a projectile after impacting an oblique *** impact produces strong vibrations on a rigid *** this impact,flexural waves travel radially outwards from the point of *** waves are used to determine the properties of the impactor with accelerometers situated on the target *** the use of two measurement plates,one can produce a ricochet and detect the velocity at the same *** are suitable for accurate momentum measurements of single ***,depending upon strike velocity and the impact angle,a ricochet can separate in multiple fragments after being *** the operational safety perspective,these fragments need to be detected,as *** approach of a coupled sensor concept was chosen to solve this *** sensors were additionally used to visualise the heat which is produced after penetrating a rubber layer pasted in front of the steel target *** this approach one was able to detect the position of *** investigations showed that the measurement system performance is better with a multiple sensor design,which includes accelerometers for the velocity,impact strength and partly the position measurement,while the thermographic sensor was used for the position measurement and partly the momentum *** investigated ammunition showed plausible fragmentation behaviour,and the results can already be used to estimate the danger potential of different ammunition *** projectiles fragment to small particles already after being deflected under a small ***,Full Metal Jacket projectiles with or without a steel core do not fragment under angles which are less than 5.The objective of the pa

关键词： Ricochet analysis Small-calibre ammunition Velocity measurement Thermography

Value of incorporating geospatial information into the prediction of on-street parking occupancy - A case study

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Geo-Spatial Information Science 2021年第3期24卷 438-457页

作者： michael Balmer Robert Weibel Haosheng Huang Department of Geography University of ZurichZurichSwitzerland Department of Geography Ghent UniversityGhentBelgium

In light of growing urban traffic,car parking becomes increasingly critical for cities to *** a result,the prediction of parking occupancy has sparked significant research interest in recent *** many external data sources have been considered in the prediction models,the underlying geographic context has mostly been ***,in order to study the contribution of geospatial information to parking occupancy prediction models,road network centrality,land use,and Point of Interest(POI)data were incorporated in Random Forest(RF)and Artificial Neural Network(ANN,specifically Feedforward Neural Network FFNN)prediction models in this *** performances were compared to a baseline,which only considers historical and temporal input ***,the influence of the amount of training data,the prediction horizon,and the spatial variation of the prediction were *** results show that the inclusion of geospatial information led to a performance improvement of up to 25%compared to the ***,as the prediction horizon expanded,predictions became less reliable,while the relevance of geospatial data *** general,land use and POI data proved to be more beneficial than road network *** amount of training data did not have a significant influence on the performance of the RF *** ANN model,conversely,achieved optimal results on a training input of 5 *** attributable to varying occupancy patterns,prediction performance disparities could be identified for different parking districts and street ***,the RF model outperformed the ANN model on all predictions.

关键词： Parking occupancy prediction on-street parking geospatial information machine learning

Machines as readers: A solution to the copyright problem

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2005年第11期6卷 1179-1187页

作者： SHAMOS michael I. School of Computer Science Carnegie Mellon University Pittsburgh PA 15213 USA Department of Computer Science University of Hong Kong Hong Kong China

Copyright and its international complications have presented a significant barrier to the Universal Digital Library （UDL）＇s mission to digitize all the published works of mankind and make them available throughout the world. We discuss the effect of existing copyright treaties and various proposals, such as compulsory licensing and the public lending fight that would allow access to copyrighted works without requiring permission of their owners. We argue that these schemes are ineffective for purposes of the UDL. Instead, making use of the international consensus that copyright does not protect facts, information or processes, we propose to scan works digitally to extract their intellectual content, and then generate by machine synthetic works that capture this content, and then translate the generated works automatically into multiple languages and distribute them free of copyright restriction.

关键词： Universal Digital Library (UDL) Copyright Digital rights management Compulsory license Berne convention Public lending right Synthetic documents Machine translation

The insect cellular immune response

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Insect Science 2008年第1期15卷 1-14页

作者： michael R. Strand Department of Entomology and Center for Emerging and Tropical Global Diseases University of Georgia Athens Georgia USA

The innate immune system of insects is divided into humoral defenses that include the production of soluble effector molecules and cellular defenses like phagocytosis and encapsulation that are mediated by hemocytes. This review summarizes current understand- ing of the cellular immune response. Insects produce several terminally differentiated types of hemocytes that are distinguished by morphology, molecular and antigenic markers, and function. The differentiated hemocytes that circulate in larval or nymphal stage insects arise from two sources： progenitor cells produced during embryogenesis and mesodermally derived hematopoietic organs. Regulation of hematopoiesis and hemocyte differentiation also involves several different signaling pathways. Phagocytosis and encapsulation require that hemocytes first recognize a given target as foreign followed by activation of downstream signaling and effector responses. A number of humoral and cellular receptors have been identified that recognize different microbes and multicellular parasites. In turn, activation of these receptors stimulates a number of signaling pathways that regulate different hemocyte functions. Recent studies also identify hemocytes as important sources Of a number of humoral effector molecules required for killing different foreign invaders.

关键词： antimicrobial peptides clotting cytokines Diptera Drosophila encapsulation,hemocytes immunity insects Lepidoptera nodulation phagocytosis

OPTIMAL CONTROL OF THE LAPLACE-BELTRAMI OPERATOR ON COMPACT SURFACES： CONCEPT AND NUMERICAL TREATMENT

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Journal of Computational Mathematics 2012年第4期30卷 392-403页

作者： michael Hinze Morten Vierling Schwerpunkt Optimierung und Approximation Universit~it Hamburg Bundesstrafle 55 20146 Hamburg Germany

We consider optimal control problems of elliptic PDEs on hypersurfaces F in R^n for n = 2, 3. The leading part of the PDE is given by the Laplace-Beltrami operator, which is discretized by finite elements on a polyhedral approximation of F. The discrete optimal control problem is formulated on the approximating surface and is solved numerically with a semi-smooth Newton algorithm. We derive optimal a priori error estimates for problems including control constraints and provide numerical examples confirming our analytical findings.

关键词： Elliptic optimal control problem Laplace-Beltrami operator Surfaces Controlconstraints Error estimates Semi-smooth Newton method.

FINITE ELEMENT EXTERIOR CALCULUS FOR PARABOLIC EVOLUTION PROBLEMS ON RIEMANNIAN HYPERSURFACES

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Journal of Computational Mathematics 2018年第6期36卷 792-832页

作者： michael Hoist Christopher Tiee Department of Mathematics University of California San Diego La Jolla CA 92093 USA

Over the last ten years, Finite Element Exterior Calculus （FEEC） has been developed as a general framework for linear mixed variational problems, their numerical approximation by mixed methods, and their error analysis. The basic approach in FEEC, pioneered by Arnold, Falk, and Winther in two seminal articles in 2006 and 2010, interprets these problems in the setting of Hilbert complexes, leading to a more general and complete understanding. Over the last five years, the FEEC framework has been extended to a broader set of problems. One such extension, due to Hoist and Stern in 2012, was to problems with variational crimes, allowing for the analysis and numerical approximation of linear and geometric elliptic partial differential equations oil Riemannian manifolds of arbitrary spatial dimension. Their results substantially generalize the existing surface finite element approximation theory in several respects. In 2014, Gillette, Hoist, and Zhu extended FEEC in another direction, namely to parabolic and hyperbolic evolution systems by combining the FEEC framework for elliptic operators with classical approaches for parabolic and hyperbolic operators, by viewing solutions to the evolution problem as lying in Bochner spaces （spaces of Banach-space valued parametrized curves）. Related work on developing an FEEC theory for parabolic evolution problems has also been done independently by Arnold and Chen. In this article, we extend the work of Gillette-Holst- Zhu and Arnold-Chen to evolution problems on Riemannian manifolds, through tile use of framework developed by Holst and Stern for analyzing variational crimes. We establish a priori error estimates that reduce to the results from earlier work in tile flat （non-criminal） setting. Some numerical examples are also presented.

关键词： FEEC Elliptic equations Evolution equations Approximation theory Inf-supconditions A priori estimates Variational crimes Equations on manifolds