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Evolving landscape and novel treatments in, metastatic castrate-resistant prostate cancer

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Asian Journal of Andrology 2013年第3期15卷 342-349页

作者： Paul J Toren martin E Gleave Department of Urologic Sciences Faculty of Medicine University of British Columbia Vancouver BC V5Z 1M9 Canada

Treatment options for castrate-resistant prostate cancer （CRPC） have advanced in recent years and significantly improved the Outlook for patients with this aggressive and lethal disease. Further understanding of the biology＇of CRPC has led to several new targeted therapies and continues to emphasize the importance of androgen receptor （AR） directed therapy. The treatment landscape is rapidly changing and further biologically rationale, biomarker-based ongoing clinical trials are needed. We review the recent results of major clinical trials in CRPC. New and investigational agents now in clinical evaluation are reviewed including inhibitors of angiogenesis, microtubules, chaperones, AR and intracellular kinases, as well as immunotherapy, radiopharmaceuticals and bone-targeted agents. The recent improvement in prognosis for CRPC brings continued optimism for further improvements. Thoughtful planning of clinical trials and further understanding of the mechanisms of resistance to therapies will allow for continued progress in patient care.

关键词： prostate cancer treatment resistance androgen receptor antagonists molecular targets

Domestication and crop evolution of wheat andbarley: Genes, genomics, and future directions

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Journal of Integrative Plant Biology 2019年第3期61卷 204-225页

作者： Matthew Haas Mona Schreiber martin Mascher Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) Gatersleben Palaeogenetics Group Institute of Organismic and Molecular Evolution Johannes Gutenberg University Mainz German Center for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig

Wheat and barley are two of the founder crops of the agricultural revolution that took place 10,000 years ago in the Fertile Crescent and both crops remain among the world's most important crops. Domestication of these crops from their wild ancestors required the evolution of traits useful to humans, rather than survival in their natural environment. Of these traits, grain retention and threshability, yield improvement, changes to photoperiod sensitivity and nutritional value are most pronounced between wild and domesticated forms. Knowledge about the geographical origins of these crops and the genes responsible for domestication traits largely pre-dates the era of nextgeneration sequencing, although sequencing will lead to new insights. Molecular markers were initially used to calculate distance(relatedness), genetic diversity and to generate genetic maps which were useful in cloning major domestication genes. Both crops are characterized by large,complex genomes which were long thought to be beyond the scope of whole-genome sequencing. However, advances in sequencing technologies have improved the state of genomic resources for both wheat and barley. The availability of reference genomes for wheat and some of its progenitors,as well as for barley, sets the stage for answering unresolved questions in domestication genomics of wheat and barley.

关键词： Domestication Wheat barley

Biomaterials for spinal cord repair

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Neuroscience Bulletin 2013年第4期29卷 445-459页

作者： Agnes E. Haggerty martin oudega Departments of Bioengineering University of Pittsburgh Departments of the Center for the Neural Basis of Cognition University of Pittsburgh Departments of Physical Medicine and Rehabilitation University of Pittsburgh Departments of Neurobiology University of Pittsburgh

Spinal cord injury （SCI） results in permanent loss of function leading to often devastating personal, economic and social problems. A contributing factor to the permanence of SCI is that damaged axons do not regenerate, which prevents the re-establishment of axonal circuits involved in function. Many groups are working to develop treatments that address the lack of axon regeneration after SCI. The emergence of biomaterials for regeneration and increased collaboration between engineers, basic and translational scientists, and clinicians hold promise for the development of effective therapies for SCI. A plethora of biomaterials is available and has been tested in various models of SCI. Considering the clinical relevance of contusion injuries, we primarily focus on polymers that meet the specific criteria for addressing this type of injury. Biomaterials may provide structural support and/or serve as a delivery vehicle for factors to arrest growth inhibition and promote axonal growth. Designing materials to address the specific needs of the damaged central nervous system is crucial and possible with current technology. Here, we review the most prominent materials, their optimal characteristics, and their potential roles in repairing and regenerating damaged axons following SCI.

关键词： spinal cord injury axon regeneration biodegradable materials extracellular matrix proteins functionalrecovery growth factor guidance injury and repair spinal motor neuron

Boosting corticospinal system synaptic plasticity to recover motor functions

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Neural Regeneration Research 2023年第10期18卷 2182-2183页

作者： Weiguo Song John H.martin Feinstein Institutes for Medical Research ManhassetNYUSA Department of Molecular Cellularand Biomedical SciencesCenter for Discovery and Innovation Neuroscience Program Graduate Center of the City University of New YorkNew YorkNYUSA

An importa nt strategy to promote voluntary movements after motor system injury is to strengthen the connections between the motor cortex and muscles by taking advantage of the plasticity of the corticospinal motor *** neuromodulation approaches are directed to activate the spinal cord and peripheral axons to strengthen muscle *** discuss in this perspective that,the cortex and spinal cord should be ta rgeted together to enhance cortex-to-musclefunction(Amer and martin,2022).

关键词： plasticity system activation

On ultrahigh temperature crustal metamorphism:Phase equilibria,trace element thermometry,bulk composition,heat sources,timescales and tectonic settings

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Geoscience Frontiers 2015年第3期6卷 311-356页

作者： David E.Kelsey martin Hand Department of Geology and Geophysics School of Physical SciencesThe University of Adelaide

Ultrahigh temperature （UHT） metamorphism is the most thermally extreme form of regional crustal metamorphism, with temperatures exceeding 900 ℃. UHT crustal metamorphism is recognised in more than 50 localities globally in the metamorphic rock record and is accepted as ＇normal＇ in the spectrum of regional crustal processes. UHT metamorphism is Wpically identified on the basis of diagnostic mineral assemblages such as sapphirine ＋ quartz, orthopyroxene ＋ sillimanite ＋ quartz and osumilite in Mg-Al- rich rock compositions, now usually coupled with pseudosection-based thermobarometry using internally-consistent thermodynamic data sets and/or Al-in-Orthopyroxene and ternary feldspar thermobarometry. Significant progress in the understanding of regional UHT metamorphism in recent years includes：（1） development of a ferric iron activity-composition thermodynamic model for sapphirine, allowing phase diagram calculations for oxidised rock compositions; （2） quantification of UHT conditions via trace element thermometry, with Zr-in-rutile more commonly recording higher temperatures than Ti-in-zircon. Rutile is likely to be stable at peak UHT conditions whereas zircon may only grow as UHT rocks are cooling. In addition, the extent to which Zr diffuses out of rutile is controlled by chemical communication with zircon; （3） more fully recognising and utilising temperature-dependent thermal properties of the crust, and the possible range of heat sources causing metamorphism in geodynamic modelling studies; （4） recognising that crust partially melted either in a previous event or earlier in a long-duration event has greater capacity than fertile, unmelted crust to achieve UHT conditions due to the heat energy consumed by partial melting reactions; （5） more strongly linking U-Pb geochronological data from zircon and monazite to P-T points or path segments through using Y ＋ REE partitioning between accessory and major phases, as well as phase diagrams incorporating Zr and REE; and （

关键词： Sapphirine + quartz P-T pseudosections Zr-in-rutile Ti-in-zircon U-Pb geochronology Subduction

Next-Generation Plant Metabolic Engineering, Inspired by an Ancient Chinese Irrigation System

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Molecular Plant 2018年第1期11卷 47-57页

作者： Rao Fu Cathie martin Yang Zhang Key Laboratory of Bio-resource and Eco-environment of Ministry of Education College of Life Sciences Sichuan University Chengdu 610064 China Department of Metabolic Biology John Innes Centre Norwich NR4 7UH UK

Specialized secondary metabolites serve not only to protect plants against abiotic and biotic challenges, but have also been used extensively by humans to combat diseases. Due to the great importance of medicinal plants for health, we need to find new and sustainable ways to improve the production of the specialized metabolites. In addition to direct extraction, recent progress in metabolic engineering of plants offers an alternative supply option. We argue that metabolic engineering for producing the second- ary metabolites in plants may have distinct advantages over microbial production platforms, and thus pro- pose new approaches of plant metabolic engineering, which are inspired by an ancient Chinese irrigation system. Metabolic engineering strategies work at three levels： introducing biosynthetic genes, using tran- scription factors, and improving metabolic flux including increasing the supply of precursors, energy, and reducing power. In addition, recent progress in biotechnology contributes markedly to better engineering, such as the use of specific promoters and the deletion of competing branch pathways. We propose that next-generation plant metabolic engineering will improve current engineering strategies, for the purpose of producing valuable metabolites in plants on industrial scales.

关键词： plant metabolic engineering secondary metabolites specialized metabolites transcription factor flux control multi-level engineering

Structural and mechanical properties of La_(1/3)NbO_3 and La_(1/3)TaO_3 thin films prepared by chemical solution deposition

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Journal of Rare Earths 2017年第11期35卷 1115-1125页

作者： Helena Brunckova Lubomir Medvecky Alexandra Kovalcikova martin Fides Erika Mudra Juraj Durisin martin Sebek Maria Kanuchova Jiri Skvarla Institute of Materials Research Slovak Academy of Sciences Watsonova 47040O1 Kosice Slovakia Technical "University of Kosice BERG Faculty Letna 9 04200 Kosice SIovakia

In this work, properties of perovskite lanthanum niobate La1/3NbO3(LN) and tantalate La1/3TaO3(LT)transparent thin films(200 nm thickness) prepared by chemical solution deposition on Pt/SiO2/Si substrates were described. The precursors and films were analyzed using FTIR and XPS spectra, XRD and SEM imaging. The both films after annealing at 1100 ℃ contained perovskite phase with a small fraction of pyrochlore LaNb5O14(in LN). The heterogeneous micro structure of LN film was composed from spherical or needle-like particles and homogeneous LT film that resulted in significant changes of their mechanical properties. The elastic modulus and hardness of these films were characterized for the first time by conventional and continuous stiffness(CSM) nanoindentation. The LT film modulus(E) and hardness(H) were higher(105.7 and 5.3 GPa) than LN(91.5 and 3.8 GPa). The effect of microstructure on mechanical properties is significant. In addition, the average Derjaguin-Muller-Toporov(DMT)-based elastic modulus of LN film surface were estimated50 GPa using AFM PeakForce QNM elastic mapping. The findings presented here can contribute to the fabrication of LN and LT films for the application to electrolytic thin film devices.

关键词： Thin films Sol-gel Perovskites Microstructures Mechanical properties

Transient Ablation Regime in Circuit Breakers

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Plasma Science and Technology 2007年第6期9卷 653-656页

作者： Alexandre martin Jean-Yves TREPANIER Marcelo REGGIO Ecole Polytechnique MontrealQuebecCanada

Nozzle wall ablation caused by high temperature electric arcs is studied in the context of high voltage SF6 circuit breakers. The simplified ablation model used in litterature has been updated to take into account the unsteady state of ablation. Ablation rate and velocity are now calculated by a kinetic model using two layers of transition, between the bulk plasma and the ablating wall. The first layer （Knudsen layer）, right by the wall, is a kinetic layer of a few mean-free path of thickness. The second layer is collision dominated and makes the transition between the kinetic layer and the plasma bulk. With this new coupled algorithm, it is now possible to calculate the temperature distribution inside the wall, as well as more accurate ablation rates.

关键词： circuit breakers electric arc ablation Teflon radiation

Comparative population genomics reveals glacial cycles to drive diversifications in tropical montane birds(Aves,Timaliidae)

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Avian Research 2022年第4期13卷 399-406页

作者： Per G.P.Ericson martin Irestedt Department of Bioinformatics and Genetics Swedish Museum of Natural HistoryP.O.Box 50007SE-10405StockholmSweden

Many bird species are specialized to live in the broadleaved,evergreen forests in the mountain regions in Southeast *** mountain habitats are not continuously distributed as the different mountain areas are separated by lowlands,which has restricted gene flow and thus contributed to the high biological diversity in this *** degree of connectivity between mountain areas has fluctuated with the Pleistocene glacial cycles,being largest during the glaciations when the mountain forests spread to lower *** we study how the intermittent periods of restricted gene flow and connectivity between the populations of five montane species of babblers(Aves,Timaliidae)in Vietnam may be traced in their *** results suggest that the babbler species in the Central Highlands have been isolated from their sister-populations in northern Vietnam for between ca.585 and 380 *** two species with populations in both the Central Highlands and the Da Lat region,we found that these split at more or less the same time(440–340 kya).We also found a significant statistical correlation between the time of the splits of these populations and the lowest altitude at which they are known to occur(no similar correlation was found with the geographic distances between populations).The populations in northern Vietnam show higher genetic variation than their counterparts in South-Central Vietnam,supporting the postulate that smaller populations may have lower genetic variation than *** accordance with this,we found the lowest genetic variation in the two species with the smallest populations in the Central *** two populations also show low levels of genomic *** results show that the south-central populations of the studied babbler species are genetically distinct from their sister-populations in northern Vietnam,providing additional argument for the long-term protection of the evergreen mountain forests in Southeast Asia.

关键词： Aves Timaliidae Babblers Demographic history Fragmented distributions Pleistocene glacial cycles Population genomics Tropical mountain forests