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CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

Signal Transduction and Targeted Therapy 2024年第8期9卷 3519-3532页

作者： Alvaro Quintanal-villalonga Kenta Kawasaki Esther Redin Fathema Uddin Swanand Rakhade vidushi Durani Amin Sabet Moniquetta Shafer Wouter R.Karthaus Samir Zaidi Yingqian A.Zhan Parvathy Manoj Harsha Sridhar Dennis Kinyua Hong Zhong Barbara P.Mello Metamia Ciampricotti Umesh K.Bhanot Irina Linkov Juan Qiu Radhika A.Patel Colm Morrsey Sanjoy Mehta Jesse Barnes Michael C.Haffner Nichlas D.Socci richard P.Koche Elisa de Stanchina Sonia Molina-Pinelo Sohrab Salehi Helena A.Yu Joseph M.Chan Charles M.Rudin Department of Medicine Thoracic Oncology ServiceMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Cancer Biology and Genetics Program Sloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA vagelos College of Physicians and Surgeons Columbia UniversityNew YorkNYUSA Weill Cornell Graduate School of Medical Sciences Weill Cornell MedicineNew YorkNYUA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Center for Epigenetics Research Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Pathology Core Facilty Department of Pathology and Laboratory MedicineMSKCCNew YorkNYUSA Antitumor Assessment Core Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Divisionsof Human Biology and Clinical Research Fred Hutchinon Cancer CenterSeattleWAUSA Deparmentof Urology University of WashingtonSeattleWAUSA Gene Editing&Screening Core Facility Memorial Sloan Kettering Cancer Center New YorkNYUSA Department of Laboratory Medicine and Pathology University of WashingtonSeattleWAUSA Bioinfomatics CoreFacility Memorial Soan Kettering Cancer CenterNew YorkNYUSA Institute of Biomedicine of Seille(Bis) HURCSCUniversidad de SevillaSevilleSpain Computational Oncology Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Well Cornell Medical College New York NYUSA Present address:Swiss Institute for Experimental Cancer Research(ISREC) School of Life SciencesEPFLLausanneSwitzerland

Neuroendocrine(NE)transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor *** to date,even if patients at high risk of transformation can be identified by the occurrence of Tumor Protein P53(TP53)and Retinoblastoma Transcriptional Corepressor 1(RB1)mutations in their tumors,no therapeutic strategies are available to prevent or delay histological *** of the cell cycle kinase Cell Division Cycle 7(CDC7)occurred in tumors during the initial steps of NE transformation,already after TP53/RB1 co-inactivation,leading to induced sensitivity to the CDC7 inhibitor ***7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the MYC Proto-Oncogen(MYC),implicated in stemness and histological *** overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype observed on targeted therapy,even in the presence of ***7 inhibition also markedly extended response to standard cytotoxics(cisplatin,irinotecan)in lung and prostate small cell carcinoma *** results nominate CDC7 inhibition as a therapeutic strategy to constrain lineage plasticity,as well as to effectively treat NE tumors de novo or after *** simurosertib clinical efficacy trials are ongoing,this concept could be readily translated for patients at risk oftransformation.

关键词： tumors markedly transformation

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Flying Capacitor Design Considerations for a 48-to-12 v,35 A Split-phase Dickson SC Converter

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Chinese Journal of Electrical Engineering 2020年第4期6卷 28-41页

作者： richard(Yue) Sun Samuel Webb Yan-Fei Liu Department of Electrical and Computer Engineering Queen's UniversityKingston K7L 3N6Canada

Switched-capacitor converters can deliver better performance,power density,and switch utilization compared to inductor-based power converters,but they suffer from current spikes during switching due to capacitor charge *** can be solved by methods such as split-phase control,which was developed to address charge redistribution in Dickson SC converters by controlling the charging and discharging of the circuit‟s flying capacitors,such that the equivalent branch voltages line up when the circuit switches ***,split-phase control is most effective at compensating for charge redistribution when all the circuit‟s flying capacitors are matched in capacitance *** between the capacitance values of the circuit flying capacitors may result in split-phase control not being able to fully compensate for charge redistribution,due to the different charge/discharge rates of the flying *** work presented in this paper provides an in-depth analysis of the sensitivity of the split-phase Dickson converter to mismatches in flying capacitor values,as well as discussions regarding the design considerations and prototype test results of a split-phase Dickson converter for high-current loads.

关键词： Switched-capacitor converter Dickson converter split-phase control capacitor mismatch

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Periodicities in the emplacement of large igneous provinces through the Phanerozoic:Relations to ocean chemistry and marine biodiversity evolution

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Geoscience Frontiers 2013年第3期4卷 263-276页

作者： Andreas Prokoph Hafida E1 Bilali richard Ernst Speedstat 19 Langstrom CrescentOttawaON K1G 5J5Canada Carleton University Department of Earth SciencesHerzberg BuildingOttawaON KIS 5B6Canada Carleton University Department of Earth SciencesHerzberg BuildingOttawaON K1S 5B6Canada ErnstGeosciences 43 Margrave AvenueOttawaON K1T 3Y2Canada

Large igneous provinces （LIPs） are considered a relevant cause for mass extinctions of marine life throughout Earth＇s history. Their flood basalts and associated intrusions can cause significant release of SO4 and CO2 and consequently, cause major environmental disruptions. Here, we reconstruct the long-term periodic pattern of LIP emplacement and its impact on ocean chemistry and biodiversity from δ34Ssulfate of the last 520 Ma under particular consideration of the preservation limits of LIP records. A combination of cross-wavelet and other time-series analysis methods has been applied to quantify a potential chain of linkage between LIP emplacement periodicity, geochemical changes and the Phanerozoic marine genera record. We suggest a mantle plume cyclicity represented by LIP volumes （v） of v= （350-770） × 103km3sin（27πt/ 170 Ma）＋（300-650）× 103 km3 sin（2πt/64.5 Ma ＋ 2.3） for t= time in Ma. A shift from the 64.5 Ma to a weaker -28-35 Ma LIP cyclicity during the Jurassic contributes together with probably independent changes in the marine sulfur cycle to less ocean anoxia, and a general stabilization of ocean chemistry and increasing marine biodiversity throughout the last -135 Ma. The LIP cycle pattern is coherent with marine biodiversity fluctuations corresponding to a reduction of marine biodiversity of -120 genera/Ma at 600 x 103 km3 LIP eruption volume. The 62-65 Ma LIP cycle pattern as well as excursion in -34Ssulfate and marine genera reduction suggest a not-vet identified found LIP event at - 440-450 Ma.

关键词： Large igneous provinces Wavelet transform Sulfur isotope Mantle plume Marine biodiversity Periodicity

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Patient-derived iPSC models of Friedreich ataxia:a new frontier for understanding disease mechanisms and therapeutic application

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Translational Neurodegeneration 2023年第1期12卷 258-280页

作者： Saumya Maheshwari Gabriela vilema-Enríquez richard Wade-Martins Department of Physiology Anatomy and GeneticsKavli Institute for Nanoscience DiscoveryUniversity of OxfordSouth Parks RoadOxford OX13QUUK

Friedreich ataxia(FRDA)is a rare genetic multisystem disorder caused by a pathological GAA trinucleotide repeat expansion in the FXN *** numerous drawbacks of historical cellular and rodent models of FRDA have caused difficulty in performing effective mechanistic and translational studies to investigate the *** recent discovery and subsequent development of induced pluripotent stem cell(iPSC)technology provides an exciting platform to enable enhanced disease modelling for studies of rare genetic *** iPSCs,researchers have created phenotypically relevant and previously inaccessible cellular models of *** models enable studies of the molecular mechanisms underlying GAA-induced pathology,as well as providing an exciting tool for the screening and testing of novel disease-modifying *** review explores how the use of iPSCs to study FRDA has developed over the past decade,as well as discussing the enormous therapeutic potentials of iPSC-derived models,their current limitations and their future direction within the field of FRDA research.

关键词： Friedreich ataxia Induced pluripotent stem cells Disease modelling Disease pathogenesis Drug development

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Thermodynamic and Environmental Assessment of Gas Flaring in the Niger Delta Region of Nigeria

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Journal of Power and Energy Engineering 2018年第12期6卷 39-56页

作者： richard v. James Howells I. Hart Barinyima Nkoi Mechanical Engineering Department Rivers State University Port Harcourt Nigeria

This paper discusses the thermodynamic and environmental assessment of flared gases in an oil field. The oil field for the case study is located in the Niger Delta region of Nigeria. The data required for this report were obtained during a nine-year period (2008-2016), which revealed production volumes, flared volumes, operating temperatures and pressures, gas compositions, gas density, and flow rates. With the data and the aid of fundamental thermodynamic equations and MATLAB program codes, analysis was carried out on combustion to ascertain the amount of flue gases. Analyses revealed that a total of 1.99175 × 1011 standard cubic feet of gas was flared during the said period, generating anthropogenics estimated at 582,319,618.1825 m3 (≈1.046 Mt) of CO2, 1,077,510,054.31 m3 (≈2.0 Mt) of water vapour, 14,960,560.91 m3 of methane emitted and contaminated the atmosphere creating serious environmental concerns. Further analyses also showed that the approximate adiabatic flame temperature is about 1965°C for the field under investigation. Exergy analyses carried out also revealed that a total of 3.6099 × 1013 kJ (36.099 TJ) of exergy was available which would have translated to 1.0189 × 1010 kWh of electrical energy for the period under investigation. Conclusively, some measures that can be taken to prevent gas flaring are that every new project on oil and gas should incorporate technical details of gas gathering and utilization plan at the conceptual and design phases of projects for gas commercialization, establishment of more gas-to-power project for gas utilization. Also Carbon capture technology should be enhanced, although the best option is flaring out based on the astronomical amount of carbon (Iv) oxide and other greenhouse gases depicted by the results. The entire work and results showed that gas flaring is undesired and pernicious because it has thermal, environmental and economic consequences.

关键词： Combustion Exergy Adiabatic Flame Temperature Gas Flaring Carbon (Iv) Oxide

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FPGA Implementation of MIMO for visible Light Communication

FPGA Implementation of MIMO for Visible Light Communication

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作者： richard Mo 上海交通大学

学位级别：硕士

As the radio frequency（RF） spectrum gets more and more congested with our constant use of Wi-Fi and 3G/4G, newer systems are being designed to alleviate if not replace some older ones. visible Light Communication（vLC）, a system in which information uses visible light as the media to transmit information has been showing promising results for indoor use. Combined with the technologies that are used in RF, it can provide high performance for relatively low costs. Techniques such as the orthogonal frequency division multiplexing modulation and multiple input multiple output（MIMO） can be adapted to work with visible light, they might not necessarily work without adjustment as the characteristics of RF waves and visible light waves *** part of a project to implement a vLC system on a FPGA hardware platform, the MIMO aspect is studied from a vLC point of view, which differs slightly from its RF counterpart. As the SNR is expected to be sufficiently high, a zero-forcing decoder with ordered successive interference cancellation is implemented. To do so, the pseudoinverse of the channel matrix needs to be computed. This is a complex process and can be done via different methods. We opt for the method using the singular value decomposition of a matrix to determine its pseudoinverse. Since resources available on hardware are more restricted than with software, hardware-efficient algorithms are used to get the most of FPGAs.

关键词： visible light communication multiple input multiple output spatial multiplexing v-BLAST zero-forcing

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Design of Polymorphic Operators for Efficient Synthesis of Multifunctional Circuits

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Journal of Computer and Communications 2016年第15期4卷 151-159页

作者： Radek Tesař václav Šimek richard Růžička Adam Crha Faculty of Information Technology Brno University of Technology Brno Czech Republic

Systematic effort dedicated to the exploration of feasible ways how to permanently come up with even more space-efficient implementation of digital circuits based on conventional CMOS technology node may soon reach the ultimate point, which is mostly given by the constraints associated with physical scaling of fundamental electronic components. One of the possible ways of how to mitigate this problem can be recognized in deployment of multifunctional circuit elements. In addition, the polymorphic electronics paradigm, with its considerable independence on a parti- cular technology, opens a way how to fulfil this objective through the adoption of emerging semiconductor materials and advanced synthesis methods. In this paper, main attention is focused on the introduction of polymorphic operators (i.e. digital logic gates) that would allow to further increase the efficiency of multifunctional circuit synthesis techniques. Key aspect depicting the novelty of the proposed approach is primarily based on the intrinsic exploitation of components with ambi- polar conduction property. Finally, relevant models of the polymorphic operators are presented in conjunction with the experimental results.

关键词： Digital Circuits Reconfiguration Multifunctional Logic Ambipolarity Polymorphic Electronics Synthesis Methods

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Solution processed MoS2-PvA composite for subbandgap mode-locking of a wideband tunable ultrafast Er：fiber laser

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Nano Research 2015年第5期8卷 1522-1534页

作者： Meng Zhang richard C. T. Howe Robert I. Woodward Edmund J. R. Kelleher Felice Torrisi Guohua Hu Sergei v. Popov J. Roy Taylor Tawfique Hasan Femtosecond Optics Group Blackett Laboratory Prince Consort Road Imperial College London London SW7 2AZ UK Cambridge Graphene Centre University of Cambridge Cambridge CB3 OFA UK

We fabricate a free-standing few-layer molybdenum disulfide （MoS2）-polymer composite by liquid phase exfoliation of chemically pristine MoS2 crystals and use this to demonstrate a wideband tunable, ultrafast mode-locked fiber laser. Stable, picosecond pulses, tunable from 1,535 nm to 1,565 nm, are generated, corresponding to photon energies below the MoS2 material bandgap. These results contribute to the growing body of work studying the nonlinear optical properties of transition metal dichalcogenides that present new opportunities for ultrafast photonic applications.

关键词： molybdenum disulfide two-dimensional materials liquid phase exfoliation polymer composites saturable absorbers ultrafast lasers

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Complications in Head and Neck Surgery 2nd ed

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2009年

作者： David W. Eisele richard v. Smith

ISBN: (纸本)9781416042204

Effectively avoiding, recognizing, and managing complications is integral to your operative success. Let a multidisciplinary team of experts in otolaryngology, plastic surgery, oral and maxillofacial surgery, and general surgery guide you through the full range of complications associated with every type of head and neck procedure . . . so you will be equipped to produce the most favorable outcomes for even the most challenging cases!

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Call for emergency action to limit global temperature increases,restore biodiversity and protect health

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Stroke & vascular Neurology 2021年第3期6卷 321-323页

作者： Lukoye Atwoli Abdullah H Baqui Thomas Benfield Raffaella Bosurgi Fiona Godlee Stephen Hancocks richard Horton Laurie Laybourn-Langton Carlos Augusto Monteiro Ian Norman Kirsten Patrick Nigel Praities Marcel GM Olde Rikkert Eric J Rubin Peush Sahni richard Smith Nicholas J Talley Sue Turale Damián vázquez East African Medical Journal NairobiKenya Journal of Health Population and NutritionBaltimoreMarylandUSA Danish Medical Journal CopenhagenDenmark PLOS Medicine CambridgeUK The BMJ LondonUK British Dental Journal LondonUK The Lancet LondonUK UK Health Alliance on Climate Change LondonUK Revista de Saúde Pública S鉶PauloBrazil International Journal of Nursing Studies LondonUK CMAJ OttawaOntarioCanada Pharmaceutical Journal LondonUK Dutch Journal of Medicine NijmegenThe Netherlands NEJM BostonMassachusettsUSA National Medical Journal of India New DelhiIndia Medical Journal of Australia NewcastleNew South WalesAustralia International Nursing Review GenevaSwitzerland Pan American Journal of Public Health WashingtonDCUSA

Wealthy nations must do much more,much *** United Nations General Assembly in September 2021 will bring countries together at a critical time for marshalling collective action to tackle the global environmental *** will meet again at the biodiversity summit in Kunming,China,and the climate conference(Conference of the Parties(COP)26)in Glasgow,*** of these pivotal meetings,we-the editors of health journals worldwide-call for urgent action to keep average global temperature increases below 1.5℃,halt the destruction of nature and protect health.

关键词： action collective faster

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