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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

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Connection Between High-Harmonic Generation and Above-Threshold Ionization

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Chinese Physics Letters 2001年第9期18卷 1199-1201页

作者： WANG Bhig-Bhig LI Xiao-Feng GAO Liang-Hui FU Pan-Ming GUO Dong-Sheng r.r.freeman Laboratory of Optical Physics Institute of Physics and Center for Condensed Matter PhysicsChinese Academy of SciencesBeijing 100080 Department of Applied Science University of CaliforniaDavisCalifornia 95616USA

Based on the nonperturbative quantum electrodynamics theory of high-order harmonic generation (HHG), we establish a direct connection between above-threshold ionization (ATI) and HHG. HHG can be described simply as an... 详细信息

关键词： simply harmonic Harmonic

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Quantum Electrodynamics Basis of Classical-Field High-Harmonic Generation Theory

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Chinese Physics Letters 2001年第9期18卷 1196-1198页

作者： WANG Bing-Bing LI Xiao-Feng GAO Liang-Hui FU Pan-Ming GUO Dong-Sheng r.r.freeman Laboratory of Optical Physics Institute of Physics and Center for Condensed Matter PhysicsChinese Academy of SciencesBeijing 100080 Department of Applied Science University of CaliforniaDavisCalifornia 95616USA

From the nonperturbative quantum electrodynamics theory, we derive the Landau-Dykhne formula which represents the quantum-mechanical formulation of the three-step model. These studies provide a basis for the classical... 详细信息

关键词： quantum formulation harmonic

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Like mother, like daughter： heritability of female richardson＇s ground squirrel Urocitellus richardsonii cortisol stress responses

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Current Zoology 2018年第2期64卷 153-163页

作者： Kevin r. BAIrOS-NOVAK Calen r rYAN Angela r. freeman W. Gary ANDErSON James F, HArE Department of Biological Sciences University of Manitoba Winnipeg Manitoba R3T 2N2 Canada Departmentof Biology University of Saskatchewan Saskatoon S7N 5E2 Saskatchewan Canada Department ofAnthropology Northwestern University Evanston 60208 Illinois USA Department of Biological Sciences Kent State University Kent 44242 Ohio USA

Activation of the hypothalamic-pituitary-adrenal （HPA） axis liberates glucocorticoids, which provides an acute indication of an individual＇s response to stressors. The heritability of the stress response in wild mammals, however, remains poorly documented. We quantified the cortisol stress response of female richardson＇s ground squirrels （rGSs） to handling and physical restraint, testing for：（1） the effects of individual age, time of day, and sample latency; （2） repeatability within individuals; （3） narrow-sense heritability; and （4） differences among individuals owing to potential genetic and/or environmental effects. We detected a positive linear relationship between baseline plasma cortisol （BL-cortisol） concentration and stress-induced plasma cortisol （Sl-cortisol） concentration that defined each individual＇s cortisol stress response. BL-cortisol, SI-cortisol, and stress response did not differ according to the time the sample was taken, or by subject age. Cortisol stress response was highly repeatable within individuals, had a mother-offspring heritability of h2 =0.40 ± 0.24 （mean ±SE）, full-sibling heritability of h2s = 0.37 ± 0.71, and half-sibling heritabil- ity of hHS^2 = 0.75 ± 1.41. Stress responses of sibling groups, immediate-family groups, and squir- rels within a given area did not differ, whereas those of individuals from more distantly related matrilines did. Our results highlight the natural variability in HPA axis reactivity among individuals by quantifying both BL- and SI-cortisol levels, demonstrate partial heritability of the stress response that is not attributable to environmental variation, and suggest that at least part of an indi- vidual＇s stress response can be accounted for by differences in matrilineal history.

关键词： glucocorticoids ground squirrel heritability hypothalamic-pituitary-adrenal axis reactivity stress response.

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Trading in your spindles for blebs： the amoeboid tumor cell phenotype in prostate cancer

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Asian Journal of Andrology 2014年第4期16卷 530-535页

作者： Samantha Morley Martin H Hager Sara G Poilan Beatrice Knudsen Dolores Di Vizio Michael r freeman Division of Cancer Biology and Therapeutics Departments of Surgery Medicine and Biomedical Sciences and The Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center Los Angeles CA Urological Diseases research Center Boston Children's Hospital Boston MA Department of Surgery Harvard Medical School Boston MA Department of Medicine David Geffen School of Medicine University of California Los Angeles CA USA.

Prostate cancer （PCa） remains a principal cause ofmortalityin developed *** no clinical interventions overcome resistance to androgen ablation therapy, management of castration resistance and metastatic disease remains largely untreatable. Metastasis is a multistep process in which tumor cells lose cell-cell contacts, egress from the primary tumor, intravasate, survive shear stress within the vasculature and extravasate into tissues to colonize ectopic sites. Tumor ceils reestablish migratory behaviors employed during nonneoplastic processes such as embryonic development, leukocyte trafficking and wound healing. While mesenchymal motility is an established paradigm of dissemination, an alternate, ＇amoeboid＇ phenotype is increasingly appreciated as relevant to human cancer.

关键词： @@

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Predictors of visual outcome in eyes with choroidal neovascularization secondary to age related macular degeneration treated with intravitreal bevacizumab monotherapy

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International Journal of Ophthalmology(English edition) 2013年第1期6卷 62-66页

作者： Jay Chhablani Jae SukKim William r freeman Igor Kozak Hai-Yan Wang Lingyun Cheng Jacob's retina Center at Shiley Eye Center University of California L V Prasad Eye Institute Department of Ophthalmology Sanggye Paik Hospital Inje University

AIM:To evaluate the predictors of visual improvement in eyes with naive choroidal neovascularization secondary to age-related macular degeneration (CNV -AMD) treated with intravitreal bevacizumab (IVB) monotherapy. METHODS:Fifty eyes with naive CNV-AMD with pretreatment best-corrected visual acuity (BCVA) better than 20/200 and treated with IVB monotherapy were evaluated. Several variables including age, sex, pre-treatment BCVA, CNV type and lesion size on fluorescein angiogram as well as SD-OCT parameters including pre-treatment central macular thickness (CMT), inner-segment/outer-segment (IS/OS) junction integrity, and external limiting membrane (ELM) integrity were analyzed to predict visual ***:On univariate regression, pretreatment ELM damage was associated with less visual improvement after treatment (P =0.0145). However, ELM damage predicted only 10% of the visual outcome. On multivariate regression, pretreatment BCVA, IS/OS junction, and ELM integrity on SD-OCT were the significant predictors for the treatment effect and together predicted 37% of visual improvement. CONCLUSION:Pretreatment BCVA, ELM and IS/OS junction integrity on SD-OCT are of significant value inpredicting the visual improvement in naive wet AMD patients treated with IVB monotherapy.

关键词： external limiting membrane age-related macular degeneration choroidal neovascularization avastin

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Even-odd harmonics generated from above-threshold ionization

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Frontiers of physics 2014年第1期9卷 69-73页

作者： Dong-Sheng Guo Jing-Tao Zhang Zhen-rong Sun Jin T. Wang Ju Gao Zhi-Wei Sun r. r. freeman State Key Laboratory of Precision Spectroscopy Department of Physics East China Normal University Shanghai 200062 China Department of Physics Southern University Baton Rouge LA 70813 USA State Key Laboratory of High Field Laser Physics Shanghai Institute of Optics and Fine Mechanics Chinese Academy of Sciences Shanghai 201800 China Jingpin Opto-Electronic Co. Jiangsu FOHO Science Park Fenhu Town Wujiang 215211 China Key Laboratory of Microgravity Institute of Mechanics Chinese Academy of Sciences Beijing 100190 China Department of Physics Ohio State University Columbus OH 43210 USA

We are reporting a theoretical prediction： The photoelectrons forming above-threshold-ionization （ATI） peaks emit both even and odd harmonics. These harmonics exhibit plateau and cut-off features similar to those o... 详细信息

关键词： strong-field laser physics above-threshold inoization high harmonic generation evenodd harmonics nonperturbative quantum electrodynamics

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Temporal pattern of resolution/recurrence of choroidal neovascularization during bevacizumab therapy for wet age-related macular degeneration

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International Journal of Ophthalmology(English edition) 2013年第5期6卷 600-605页

作者： Haiyan Wang Giulio Barteselli William r.freeman Su Na Lee Jay Chhablani Sharif El-Emam Lingyun Cheng Department of Ophthalmology Jacobs Retina Center at Shiley Eye CenterUniversity of California San Diego

AIMTo characterize temporal pattern of resolution and recurrence of naive choroidal neovascularization (CNV) secondary to wet age-related macular degeneration (AMD) treated with intravitreal bevacizumab on as needed r... 详细信息

关键词： bevacizumab age-related macular degeneration recurrence anti-vascular endothelial growth factor therapy

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It’s Not Just the Money: Why Consumers Do Not Purchase Pharmacist-Provided Services

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Pharmacology & Pharmacy 2014年第6期5卷 570-576页

作者： Patricia r. freeman Mikael Jones Karen Blumenschein Department of Pharmacy Practice and Science University of Kentucky College of Pharmacy Lexington USA

The reimbursement model for pharmaceutical care remains a barrier to successful widespread implementation of pharmacist-provided services. In some instances, community pharmacists have been successful in obtaining direct compensation for services from patients;however, evidence suggests that lack of patient demand for pharmacist-services may ultimately undermine the campaign for widespread third-party payment. The purpose of this study is to conduct a secondary analysis of data indicating consumer/patients’ rationale for not purchasing pharmacist-provided disease management services when offered the opportunity to do so in community pharmacies. Our review of the data indicates that while financial concerns are clearly important in consumer demand for pharmacist-provided services, other considerations exist. The consumer/patient belief that pharmacist-provided services are duplicative or that these services are not needed are significant barriers to overcome. Intensive education and marketing campaigns are needed to sway consumer opinion on the value of pharmacist-provided services.

关键词： Pharmacist-Provided Services Pharmaceutical Care Compensation

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Field-resolved high-order sub-cycle nonlinearities in a terahertz semiconductor laser

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Light(Science & Applications) 2021年第12期10卷 2531-2540页

作者： J.riepl J.raab P.Abajyan H.Nong J.r.freeman L.H.Li E.H.Linfield A.G.Davies A.Wacker T.Albes C.Jirauschek C.Lange S.S.Dhillon r.Huber Department of Physics University of RegensburgRegensburgGermany Laboratoire de Physique de l’Ecole Normale Supérieure ENSUniversitéPSLCNRSSorbonne UniversitéUniversitéde ParisParisFrance School of Electronic and Electrical Engineering University of LeedsWoodhouse LaneLeedsUK Mathematical Physics and NanoLund Lund UniversityLundSweden Department of Electrical and Computer Engineering Technical University of MunichMunichGermany Department of Physics TU Dortmund UniversityDortmundGermany

The exploitation of ultrafast electron dynamics in quantum cascade lasers(QCLs)holds enormous potential for intense,compact mode-locked terahertz(THz)sources,squeezed THz light,frequency mixers,and comb-based metrology *** the important sub-cycle dynamics have been notoriously difficult to access in operational THz ***,we employ high-field THz pulses to perform the first ultrafast two-dimensional spectroscopy of a free-running THz *** incoherent and coherent nonlinearities up to eight-wave mixing are detected below and above the laser *** data not only reveal extremely short gain recovery times of 2 ps at the laser threshold,they also reflect the nonlinear polarization dynamics of the QCL laser transition for the first time,where we quantify the corresponding dephasing times between 0.9 and 1.5 ps with increasing bias currents.A density-matrix approach reproducing the emergence of all nonlinearities and their ultrafast evolution,simultaneously,allows us to map the coherently induced trajectory of the Bloch *** observed high-order multi-wave mixing nonlinearities benefit from resonant enhancement in the absence of absorption losses and bear potential for a number of future applications,ranging from efficient intracavity frequency conversion,mode proliferation to passive mode locking.

关键词： polarization mixer cycle

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