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Investigation of androgen receptor-dependent alternative splicing has identified a unique subtype of lethal prostate cancer

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Asian Journal of Andrology 2023年第3期25卷 296-308页

作者： Sean Seltzer Paresa n Giannopoulos Tarek A Bismar Mark Trifiro Miltiadis Paliouras Lady Davis Institute for Medical Research Segal Cancer Centre-Jewish General HospitalMontrealQC H3T 1E2Canada Cumming School of Medicine Department of Pathology and Laboratory MedicineUniversity of CalgaryCalgaryAB T2N 1N4Canada Department of Medicine Division of Experimental MedicineMcGill UniversityMontrealQC H4A 3J1Canada Department of Oncology McGill UniversityMontrealQC H4A 3T2Canada

A complete proteomics study characterizing active androgen receptor(AR)complexes in prostate cancer(PCa)cells identified a diversity of protein interactors with tumorigenic annotations,including known RnA splicing ***,we chose to further investigate the functional role of AR-mediated alternative RnA splicing in PCa disease *** selected two AR-interacting RnA splicing factors,Src associated in mitosis of 68 kDa(SAM68)and DeAD(Asp-Glu-Ala-Asp)box helicase 5(DDX5)to examine their associative roles in AR-dependent alternative RnA *** assess the true physiological role of AR in alternative RnA splicing,we assessed splicing profiles of LnCaP PCa cells using exon microarrays and correlated the results to PCa clinical *** a result,we were able to highlight alternative splicing events of clinical *** use of exon-mini gene cassettes illustrated hormone-dependent AR-mediated exon-inclusion splicing events with SAM68 or exon-exclusion splicing events with DDX5 *** physiological significance in PCa was investigated through the application of clinical exon array analysis,where we identified exon-gene sets that were able to delineate aggressive disease progression profiles and predict patient disease-free outcomes independently of pathological clinical *** a clinical dataset with patients categorized as prostate cancer-specific death(PCSD),these exon gene sets further identified a select group of patients with extremely poor disease-free ***,these results strongly suggest a nonclassical role of AR in mediating robust alternative RnA splicing in ***,AR-mediated alternative spicing contributes to aggressive PCa progression,where we identified a new subtype of lethal PCa defined by AR-dependent alternative splicing.

关键词： alternative RnA splicing androgen receptor exon-gene sets lethal prostate cancer subtype prostate cancer

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外加颗粒增强非晶复合材料研究进展

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兵器装备工程学报 2024年第9期45卷 65-74页

作者：刘威苏小红胡会娥迟钧瀚金浩宇海军工程大学基础部武汉430033 海军旅顺装备技术质量监测站辽宁旅顺116041

外加颗粒是提高非晶合金室温韧性的有效手段之一,同时外加颗粒的引入也促进了功能非晶复合材料的开发。根据外加颗粒增强非晶复合材料的塑性变形机制,综述了外加颗粒的脆韧性、颗粒尺寸对非晶复合材料的室温韧性、屈服强度等力学性能的... 详细信息

外加颗粒是提高非晶合金室温韧性的有效手段之一,同时外加颗粒的引入也促进了功能非晶复合材料的开发。根据外加颗粒增强非晶复合材料的塑性变形机制,综述了外加颗粒的脆韧性、颗粒尺寸对非晶复合材料的室温韧性、屈服强度等力学性能的具体影响研究进展。针对外加颗粒增强非晶复合材料制备中存在的分散问题、两相结合问题以及成分偏析问题进行了分析和展望。对具有一定功能的外加颗粒增强非晶复合材料的研究现状进行了概述。

关键词：外加颗粒非晶复合材料室温韧性制备方法功能复合材料

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High density lipoprotein as a therapeutic target:Focus on its functionality

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BIOCeLL 2023年第11期47卷 2361-2383页

作者： LeOnARDO GÓMeZ ROSSO BeLÉn DAVICO eZeQUIeL LOZAnO CHIAPPe WALTeR TeTZLAFF LAURA BOeRO FeRnAnDO BRITeS MAXIMILIAnO MARTÍn School of Pharmacy and Biochemistry Laboratory of Lipids and AtherosclerosisDepartment of Clinical BiochemistryUniversity of Buenos AiresNational Scientific and Technical Research Council(CONICET)Buenos Aires1113Argentina

Cardiovascular diseases(CVDs)are the leading cause of death *** are a group of disorders of the heart and blood vessels and include coronary heart disease,cerebrovascular disease and rheumatic heart disease among other *** are multiple independent risk factors for CVD,including hypertension,age,smoking,insulin resistance,elevated low-density lipoprotein cholesterol(LDL-C)levels,and triglyceride ***-C levels have traditionally been the target for therapies aimed at reducing CVD *** density lipoprotein(HDL)constitutes the only lipoprotein fraction with atheroprotective *** HDL-targeted therapies have focused on increasing HDL-C ***,clinical trials have shown that raising HDL-C with niacin failed to achieve CVD reduction.A possible explanation for these findings is that these drugs could interfere with lipid metabolism and cause alterations in HDL structure and composition,leading to loss of *** a result,targeting HDL-C levels would be insufficient to achieve CVD risk reduction,making HDL functionality a more desirable focus for HDL-directed *** are several drugs which show the potential to improve HDL *** drugs include molecules already approved for human use,such as statins and niacin,and particularly,compounds currently undergoing development such as apolipoprotein A-I mimetics and reconstituted HDL *** therapies show promising potential to improve HDL functionality *** therapeutic strategies should incorporate HDL functionality as a main target of interest.

关键词： HDL Cholesterol efflux rHDL Apo A-I mimetics Statins Paraoxonase

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Field curing methods and storage duration affect the quality of hay from six rangeland grass species in Kenya

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ecological Processes 2016年第1期5卷 32-37页

作者： O.K.Koech R.n.Kinuthia G.n.Karuku S.M.Mureithi R.Wanjogu Department of Land Resource Management and Agricultural Technology Range Management SectionUniversity of NairobiP.O.Box 209053-00625NairobiKenya national Irrigation Board Mwea Irrigation Agricultural Development(MIAD)CentreP.O.Box 21010303 WanguruKenya

Introduction:Rangelands are important source of pasture for livestock in Kenya since time immemorial to pastoral ***,seasonality on forage availability has been a big challenge in meeting animals’feed *** demands harvest and storage of pastures for use during dry *** making has been done to bridge this forage deficit ***,hay quality in the rangelands is affected by curing methods,phonological stage at harvest,and the storage *** therefore evaluated the effect of field curing and storage duration on the quality(Crude Protein(CP))of hay from six rangeland grasses in ***:The grasses evaluated are Chloris roxburghiana,eragrostis superba,enteropogon macrostachyus,Cenchrus ciliaris,Chloris gayana,and Sorghum *** grasses are the common species in the rangelands of Kenya and have been promoted in the past for hay making and reseeding *** grasses were harvested at the mature flowering stage(12 weeks phenological stage),which is a period that provides high biomass without much effect on quality as practiced in the study *** grasses were then cured in the field for 1,2,and 3 days before baling and stored indoors for 12,24,and 36 *** were taken for CP content determination at the three periods following Macro-Kjeldahl ***:There was significant decline(p≤0.05)in crude protein content in all the grass species with storage *** period did not affect the CP content for all the species at a given storage period;however,3 days curing changed the hay color from green to brownish which reduces palatability and consequently reduced feed *** period of over 12 weeks adversely lowered CP to less than 6% for all the species which is the required minimum level for animal under production and *** had significantly higher decline in CP after 24 weeks storage compared to the other ***:Therefore,hay from the six grass spec

关键词： Grass quality Range grasses Semi-arid rangelands Grass storage Grass curing Kenya

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Promise of metformin for preventing age-related cognitive dysfunction

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neural Regeneration Research 2022年第3期17卷 503-507页

作者： Leelavathi n.Madhu Maheedhar Kodali Ashok K.Shetty Institute for Regenerative Medicine Department of Molecular and Cellular MedicineTexas A&M University College of MedicineCollege StationTXUSA

The expanded lifespan of people,while a positive advance,has also amplified the prevalence of age-related disorders,which include mild cognitive impairment,dementia,and Alzheimer's ***,competent therapies that could improve the healthspan of people have great *** of the dietary and pharmacological approaches that augment the lifespan could also preserve improved cognitive function in old ***,a drug widely used for treating diabetes,is one such candidate that could alleviate age-related cognitive ***,the possible use of metformin to alleviate age-related cognitive dysfunction has met with conflicting results in human and animal *** most clinical studies have suggested the promise of metformin to maintain better cognitive function and reduce the risk for developing dementia and Alzheimer's disease in aged diabetic people,its efficacy in the nondiabetic population is still ***,a previous animal model study implied that metformin could adversely affect cognitive function in the ***,a recent animal study using multiple behavioral tests has reported that metformin treatment in late middle age improved cognitive function in old *** study also revealed that cognitionenhancing effects of metformin in aged animals were associated with the activation of the energy regulator adenosine monophosphate-activated protein kinase,diminished neuroinflammation,inhibition of the mammalian target of rapamycin signaling,and augmented autophagy in the *** proficiency of metformin to facilitate these favorable modifications in the aged hippocampus likely underlies its positive effect on cognitive ***,additional studies probing the outcomes of different doses and durations of metformin treatment at specific windows in the middle and old age across sex in nondiabetic and non-obese prototypes are required to substantiate the promise of metformin to maintain better cognitive fun

关键词： activated microglia aging autophagy cognitive dysfunction memory metformin mTOR signaling neuroinflammation

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Arsenic and sulfur nanoparticle synthesis mimicking environmental conditions of submarine shallow-water hydrothermal vents

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Journal of environmental Sciences 2022年第1期34卷 301-312页

作者： Vicente Durán-Toro Kurosch Rezwan Solveig I.Bühring Michael Maas MARUM–Center for Marine environmental Sciences University of BremenBremen 28359Germany Advanced Ceramics University of BremenBremen 28359Germany MAPeX-Center for Materials and Processes University of BremenBremen 28359Germany

Arsenic and sulfur mineralization is a natural phenomenon occurring in hydrothermal systems where parameters like temperature and organic matter(OM)can influence the mobilization of the toxic metalloid in marine *** the present study we analyze the influence of temperature and OM(particularly sulfur-containing additives)on As and S precipitation based on the recent discovery of As-rich nanoparticles in the hydrothermal system near the coast of the Greek island *** this end,we experimentally recreate the formation of amorphous colloidal particles rich in As and S via acidification(pH 3–4)of aqueous precursors at various *** higher temperatures,we observe the formation of monodisperse particles within the first 24 h of the experiment,generating colloidal particles with diameters close to 160 *** S:As ratio and particle size of the synthetized particles closely correlates with val.e. for As_(x)S_(y)particles detected in the hydrothermal system off ***,organic sulfur containing additives(cysteine and glutathione,GSH)are a key factor in the process of nucleation and growth of amorphous colloidal As_(x)S_(y)particles and,together with the temperature gradient present in shallow hydrothermal vents,dictate the stabilization of As-bearing nanomaterials in the *** on these findings,we present a simple model that summarizes our new insights into the formation and mobility of colloidal As in aquatic *** this context,amorphous As_(x)S_(y)particles can present harmful effects to micro-and macro-biota not foreseen in bulk As material.

关键词： Biomineralization Milos Hydrothermal vent Arsenic Sulfur nanoparticles ecotoxicology

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基于变压器磁调谐的双模W波段VCO

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半导体技术 2024年第2期49卷 164-170页

作者：朱承同徐雷钧谢月娥陈元平江苏大学物理与电子工程学院江苏镇江212013 江苏大学电气信息工程学院江苏镇江212013

提出了一种基于变压器的用于无变容管W波段压控振荡器(VCO)的磁调谐技术。通过控制变压器磁调谐线圈所连接MOS管的开关状态,引入了四个重叠的频率子带。所提出的可切换的六线圈变压器采用40 nm CMOS工艺的顶层厚金属设计,实现了较高的... 详细信息

提出了一种基于变压器的用于无变容管W波段压控振荡器(VCO)的磁调谐技术。通过控制变压器磁调谐线圈所连接MOS管的开关状态,引入了四个重叠的频率子带。所提出的可切换的六线圈变压器采用40 nm CMOS工艺的顶层厚金属设计,实现了较高的输出频率稳定性和谐振腔品质因数。所采用的技术在对相位噪声的不利影响最小的情况下扩展了调谐范围,实现了无变容管W波段VCO的宽调谐范围和低功耗。所设计的双模W波段VCO输出频率为84.2~107.5 GHz,频率调谐范围大于24%,在1 V电源电压下功耗仅6.1 mW,在10 MHz偏移处的相位噪声为-107.203~-97.875 dBc/Hz。

关键词：变压器磁调谐无变容管 W波段压控振荡器(VCO)

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Carbonate oxygen isotope record from Lake Hovsgol,nW Mongolia,lake level changes and the link to atmospheric circulation changes during the past 25 kyr

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地球环境学报 2011年第1期 322-323页

作者： Prokopenko AA Solotchina e P Zhdanova Anastasia n Kuzmin M I Department of earth and Ocean Sciences University of South Carolina Institute of Geochemistry Siberian Branch of Russian Academy of Sciences Institute of Geology and Mineralogy Siberian Branch of Russian Academy of Sciences

Lake Hovsgol at 51°n in nW Mongolia is located in a rift basin with a small confined *** lake serves as a sensitive "water gauge" in a region dominated by westerly atmospheric circulation in summer and by the Siberian（Asiatic） High pressure system in *** most lakes in the region,Hovsgol remained relatively deep during the last glacial-interglacial transition,preserving a continuous record of finely-laminated *** in the neighboring Lake Baikal,sediments of Lake Hovsgol from the last glacial-interglacial transition contain both endogenic carbonates and ostracod *** a result,these sediments represent the first regional paleoclimate archive suitable for a study of past changes in the oxygen isotope composition of lake waters from δ;O of carbonates deposited in a stable deepwater lacustrine *** we present a synthesis of Lake Hovsgol data on changes in lake level,hydrologic budget and carbonate oxygen isotope composition to arrive at a new understanding of changes in westerly atmospheric circulation over continental interior of Asian during the past 25 cal *** show that the dramatic lowstand of the lake on the order of;00 m dates back to 22 cal ka BP,i.e.,pre-dates the interval typically recognized as last glacial maximum（LGM）.Since this major lowstand event,the lake level was rising more or less steadily with an intermediate lowstand on the order of;00 m at 16 cal ka *** positive trend in the hydrologic balance during deglaciation is consistent with the mineralogy of endogenic carbonates from X-ray diffraction analysis:the abundance of Mg-calcite and the content of Mg in calcite steadily decreased in Hovsgol sediments since the last *** isotope analysis of carbonates in Lake Hovsgol lowstand facies shows that oxygen isotope ratios of lake water were not controlled by either evaporative enrichment in the closed basin or by the hypothesized input of glacial ***,changes in the composition of atm

关键词： Lake Carbonate oxygen isotope record from Lake Hovsgol,nW Mongolia,lake level changes and the link to atmospheric circulation changes during the past 25 kyr

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A non-conventional hybrid numerical approach with multi-dimensional random sampling for cocaine abuse in Spain

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International Journal of Biomathematics 2018年第8期11卷 289-305页

作者： Maha A. Mohammed n. F. M. noor A. I. n. Ibrahim Z. Sir Department of Mathematics Ibn-Al-Haitham College of education University of Baghdad 477146 Baghdad Iraq Institute of Mathematical Sciences Faculty of Science University of Malaya 50603 Kuala Lumpur Malaysia

This paper introduces a non-conventional approach with multi-dimensional random sampling to solve a cocaine abuse model with statistical probability. The mean Latin hypercube finite difference (MLHFD) method is proposed for the first time via hybrid integration of the classical numerical finite difference (FD) formula with Latin hypercube sampling (LHS) technique to create a random distribution for the model parameters which are dependent on time t. The LHS technique gives advantage to MLHFD method to produce fast variation of the parameters' val.e. via number of multidimensional simulations (100, 1000 and 5000). The generated Latin hypercube sample which is random or non-deterministic in nature is further integrated with the FD method to complete one cycle of LHS-FD simulation iteration. This process is repeated until n final iterations of LHS-FD are obtained. The means of these n final solutions (MLHFD solutions) are tabulated, graphed and analyzed. The numerical simulation results of MLHFD for the SeIR model are presented side-by-side with deterministic solutions obtained from the classical FD scheme and homotopy analysis method with Pade approximation (HAM-Pade). The present MLHFD results are also compared with the previous non-deterministic statistical estimations from 1995 to 2015. Good agreement between the two is perceived with small errors. MLHFD method can be used to predict future behavior, range and prediction interval for the epidemic model solutions. The expected profiles of the cocaine abuse subpopulations are projected until the year 2045. Both the statistical estimations and the deterministic results of FD and HAM-Pade are found to be within the MLHFD prediction intervals for all the years and for all the subpopulations considered.

关键词： epidemic model finite difference method Latin hypercube sampling ordinarydifferential equation prediction interval random distribution SeIR

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Leaching kinetics in cyanide media of Ag contained in the industrial mining-metallurgical wastes in the state of Hidalgo, Mexico

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International Journal of Mining Science and Technology 2014年第5期24卷 689-694页

作者： Juan Hernandez Francisco Patino Isauro Rivera Iván Alejandro Reyes Misrael Uriel Flores Julio Cesar Juarez Martín Reyes Research Centre in Materials and Metallurgy Autonomous University of Hidalgo Pachuca 42184 Mexico

The leaching kinetics in cyanide media of the silver contained in the Dos Carlos waste tailings at the City of Pachuca de Soto, Hidalgo State, Mexico were carried out. The used material contained the following chemical composition: 56 10-6of Ag, 0.6 10 6of Au and 70.43%(by weight) of SiO2; 7.032%(by weight) of Al2O3; 2.69%(by weight) of Fe; 0.46%(by weight) of Mn; 3.98%(by weight) of K2O; 3.34%(by weight) of CaO; 2.50%(by weight) of na2O; 0.04%(by weight) of Zn; 0.026%(by weight) of Pb. The mineralogical phases present were the following: Silica, albite, argentite, berlinite, orthoclase, potassium jarosite, and natrojarosite. In the leaching kinetics in cyanide media, and under the studied conditions,the effect of the Cn concentration on the reaction rate has no effect on the whole process of alkaline cyanidation, of which the reaction order is n 0. Temperature has an effect on the cyanidation rate of the reaction, with an activation energy of 47.9 KJ/mol. At the same time, when the particle size decreases there is an increase in the reaction rate, which is inversely proportional to the particle diameter; when increasing the naOH concentration there is an increase in the reaction rate Kexp, with a reaction order(n) of 0.215 under the studied ranges.

关键词： Silver Waste tailings Cyanidation Leaching

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