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Multidisciplinary perspective of hepatocellular carcinoma: A pacific Northwest experience

World Journal of Hepatology 2015年第11期7卷 1460-1483页

作者： Matthew M Yeh Raymond S Yeung Smith Apisarnthanarax Renuka Bhattacharya Carlos Cuevas william p harris Tony Lim Kiat Hon Siddharth A padia James O park Kevin M Riggle Sayed S Daoud Department of pathology University of Washington School of Medicine Department of Medicine University of Washington School of Medicine Northwest Liver Research program Depart-ment of Surgery University of Washington School of Medicine Department of Radiation Oncology University of Washington School of Medicine Department of Radiology University of Washington School of Medicine Seattle Department of pathology Singapore General Hospital Department of pharmaceutical Sciences Washington State University Health Sciences

Hepatocellular carcinoma(HCC) is the most rapidly increasing type of cancer in the United States. HCC is a highly malignant cancer, accounting for at least 14000 deaths in the United States annually, and it ranks third as a cause of cancer mortality in men. One major difficulty is that most patients with HCC are diagnosed when the disease is already at an advanced stage, and the cancer cannot be surgically removed. Furthermore, because almost all patients have cirrhosis, neither chemotherapy nor major resections are well tolerated. Clearly there is need of a multidisciplinary approach for the management of HCC. For example, there is a need for better understanding of the fundamental etiologic mechanisms that are involved in hepatocarcinogenesis, which could lead to the development of successful preventive and therapeutic modalities. It is also essential to define the cellular and molecular bases for malignant transformation of hepatocytes. Such knowledge would:(1) greatly facilitate the identification of patients at risk;(2) prompt efforts to decrease risk factors; and(3) improve surveillance and early diagnosis through diagnostic imaging modalities. possible benefits extend also to the clinical management of this disease. Because there are many factors involved in pathogenesis of HCC,this paper reviews a multidisciplinary perspective of recent advances in basic and clinical understanding of HCC that include: molecular hepatocarcinogenesis, noninvasive diagnostics modalities, diagnostic pathology, surgical modality, transplantation, local therapy and oncological/target therapeutics.

关键词： Genetic alterations Epigenetic alterations Diagnostic pathology Diagnostic imaging Surgicalmodality Liver transplantation Locoregional therapy Sorafenib Hepatocellular carcinoma Liver resection

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The Jurassic-Cretaceous boundary： An age-old correlative enigma

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Episodes 2008年第4期31卷 423-428页

作者： william A.p. Wimbledon Department of Earth Sciences University of Bristol Queens Road Bristol BS8 United Kingdom

The Jurassic-Cretaceous boundary interval has been problematic since the start of stratigraphic study. This is reflected in different stage names being employed in Boreal and Tethyan realms below and above the putative boundary. Despite attempts at homogenisation where stage terminology is concerned, correlative precision over long distances at or close to a boundary has not yet been achieved. But the new Berriasian/ J-K boundary working-group of the Cretaceous Subcommission is now attempting to remedy this situation.

关键词：侏罗纪白垩纪交界时期地层学

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Testosterone therapy in men with prostate cancer： literature review, clinical experience, and recommendations

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Asian Journal of Andrology 2015年第2期17卷 206-211,I0007页

作者： Abraham Morgentaler william p Conners III Men's Health Boston 200 Boylston St Suite A309 Chestnut Hill MA 02467 USA.

For several decades any diagnosis of prostate cancer （pCa） has been considered an absolute contraindication to the use of testosterone （T） therapy in men. Yet this prohibition against T therapy has undergone recent re-examination with refinement of our understanding of the biology of androgens and pCa, and increased appreciation of the benefits of T therapy. A reassuringly low rate of negative outcomes has been reported with T therapy after radical prostatectomy （Rp）, radiation treatments, and in men on active surveillance. Although the number of these published reports are few and the total number of treated men is low, these experiences do provide a basis for consideration of T therapy in selected men with pCa. For clinicians considering offering this treatment, we recommend first selecting patients with low grade cancers and undetectable prostate-specific antigen following Rp. Further research is required to define the safety of T therapy in men with pCa. However, many patients symptomatic from T deficiency are willing to accept the potential risk of pCa progression or recurrence in return for the opportunity to live a fuller and happier life with T therapy.

关键词： androgen deprivation androgens hypogonadism prostate cancer prostate-specific antigen testosterone testosterone therapy

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Estimating ancestral distributions of lineages with uncertain sister groups:a statistical approach to Dispersal-Vicariance Analysis and a case using Aesculus L.(Sapindaceae) including fossils

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Journal of Systematics and Evolution 2009年第5期47卷 349-368页

作者： A.J.harris North Carolina State University Department of Plant Biology

We propose a simple statistical approach for using Dispersal-Vicariance Analysis(DIVA) software to infer biogeographic histories without fully bifurcating *** this approach,ancestral ranges are first optimized for a sample of Bayesian *** probability p of an ancestral range r at a node is then calculated as p(rY) = n t=1 F(rY)t pt where Y is a node,and F(rY) is the frequency of range r among all the optimal solutions resulting from DIVA optimization at node Y,t is one of n topologies optimized,and pt is the probability of topology *** Y is a hypothesized ancestor shared by a specific crown lineage and the sister of that lineage "x",where x may vary due to phylogenetic uncertainty(polytomies and nodes with posterior probability provide inference of the geographic origins of the specific crown group of *** approach takes into account phylogenetic uncertainty as well as uncertainty from DIVA *** is an extension of the previously described method called Bayes-DIVA,which pairs Bayesian phylogenetic analysis with biogeographic analysis using ***,we show that the probability p of an ancestral range at Y calculated using this method does not equate to pp*F(rY) on the Bayesian consensus tree when both variables are pp is the posterior probability and F(rY) is the frequency of range r for the node containing the specific crown *** tested our DIVA-Bayes approach using Aesculus L.,which has major lineages unresolved as a *** inferred the most probable geographic origins of the five traditional sections of Aesculus and of Aesculus californica *** examined range subdivisions at parental nodes of these ***,we used the DIVA-Bayes data from Aesculus to quantify the effects on biogeographic inference of including two wildcard fossil taxa in phylogenetic *** analysis resolved the geographic ranges of the pare

关键词： Aesculus biogeography DIVA fossil wildcards MrBayes phylogenetic uncertainty.

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Measuring magnetic declination with a compass, virtual globes and a global positioning system

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International Journal of Digital Earth 2009年第1期2卷 31-43页

作者： william p.O’Brien Jr physics Department Southwestern UniversityGeorgetownTexas78626USA

Earth’s magnetic declination was experimentally measured at 15 sites in western USA from Alaska to Texas;each site exhibited a large linear feature identifiable in virtual globe imagery(NASA’s World Wind or Google Earth).The difference between the geographic bearing of the linear feature measured directly on a virtual globe image and the magnetic bearing of the same linear feature measured on the ground with a compass defines the magnetic declination d for that *** all 15 sites,d values,determined by this differencing procedure,ranged from about 208 to 58 E and fell within 18(over half within 0.58)of expected *** positioning system(GpS)data recorded at most sites and plotted on virtual globe images aided in the identification of relevant *** straightforward method for determining magnetic declination using virtual globe software and a compass provides a contemporary geospatial field/laboratory activity that dramatically elucidates and contrasts features of magnetic and geographic coordinate systems for students in various disciplines involving geomagnetism,navigation,geography or spherical polar geometry.

关键词： Earth observation GpS magnetic declination geophysics

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Advances in Regioselective Functionalization of Endohedral Metallofullerenes

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Chinese Journal of Chemistry 2023年第16期41卷 2025-2034页

作者： Yanbang Li Yue Sun william p.Kopcha Jianyuan Zhang Deportment of Chemistry and Chemical Biology RutgersThe Stote University of New Jersey123 Bevier RdPiscotawayNJ 08854USA

Comprehensive Summary Endohedral metallofullerenes(EMFs)are a family of molecules with metal clusters or ions encapsulated inside a fullerene *** unique structures provide a powerful interface for organic chemists to manipulate metal *** a decade ago,many reactions on empty fullerenes were adopted for EMFs,resulting in a series of reactions that are well-established and reviewed in the *** recent years,new topics have emerged in EMF ***,new addition reactions were developed,notably some that are not based on known empty-fullerene ***,considerable progress has been made on regioselective multi-additions on EMFs.

关键词： Regioselectivity Fullerenes Crystal growth Cycloaddition Rare earth

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Molecular markers in prostate cancer part Ⅱ： potential roles in management

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Asian Journal of Andrology 2009年第1期11卷 22-27页

作者： Sachin Agrawal Krishnaji p. patil william D. Dunsmuir Department of Urology St Peters Hospital Chertsey KT16 OPZ UK

predicting treatment responses in advanced prostate cancer （pCa） currently centres on prostate-specific antigen （pSA） kinetics and on being able to visualize measurable changes in imaging modalities. New molecular markers have emerged as potential diagnostic and prognostic indicators; these were summarized in part I of this review in the Asian Journal ofAndrology. A number of molecular markers are now being used to enhance pCa imaging and staging. However, management options for advanced and hormone-resistant pCa （HRpC） are limited and additional therapeutic options are needed. Molecular markers have been proposed as potential therapeutic targets using gene therapy and immunomodulation. Additionally, markers identified in early pCa and precursor lesions may offer novel targets for chemoprevention and vaccine development. This review summarizes the current advances regarding the roles of these markers in the management of pCa.

关键词： genetics management molecular prostate cancer

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In situ measurement of ECM rheology and microheterogeneity in embedded and overlaid 3D pancreatic tumor stroma co-cultures via passive particle tracking

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Journal of Innovative Optical Health Sciences 2017年第6期10卷 26-34页

作者： Dustin p.Jones william Hanna Gwendolyn M.Cramer Jonathan p.Celli Department of physics University of Massachusetts Boston Boston MA 02215USA

Tumor growth is regulated by a diverse set of extraellular infuences,including paracrine crosstalk with stromal partners,and biophysical interactions with surrounding cells and *** elucidating the role of physical force and the mechanical properties of the extracellular matrix(ECM)itself as regulators of tumor growth and invasion have been greatly catalyzed by the use of in ritro three-dimensional(3D)tumor *** systems provide the ability to systematically isolate,manipulate,and evaluate impact of stromal components and extracellular mechanics in a platform that is both conducive to imaging and biologically ***,recognizing that mechanoregulatory crosstalk is bi-directional and fully utilizing these models requires complementary methods for in situ measurements of the local mechanical ***,in 3D tumor/fbroblast co-culture models of pancreatic canocer,a discase characterized by its prominent stromal involvement,we evaluate the use of particle-tracking microrhoology to probe dynamic mechanical *** videos of fuorescently labeled polystyrene micro-spheres embedded in ollagen I ECM,we measure spatiotemporal changes in the Brownian motion of probes to report local ECM shear modulus and *** approach reveals st ffening of collagen in fibroblast co-cultures relative to cultures with cancer cells only,which exhibit degraded ECM with heterogeneous *** further show that these effects are dependent on culture geometry with contrast ing behavior for embedded and overlay *** addition to potential application to screening stroma targeted therapeutics,this work also provides insight into how the compoition and plating geometry impact the mechanical propertios of 3D cell cultures that are increasingly widey used in cancer biology.

关键词： Microrheology 3D tumor models matrix remodeling mechanobiology stromal depletion

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Separation of atropisomers by chiral liquid chromatography and thermodynamic analysis of separation mechanism

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Journal of pharmaceutical Analysis 2017年第3期7卷 156-162页

作者： Ling Zhang Yue Hu Elizabeth Galella Frank p. Tomasella william p. Fish Chemical and Synthetic Development Bristol-Myers Squibb Co.New BrunswickNJ 08903USA Drug product Science and Technology Bristol-Myers Squibb Co.New BrunswickNJ 08903USA

In the pharmaceutical industry, the analysis of atropisomers is of considerable interest from both scientific and regulatory perspectives. The compound of interest contains two stereogenic axes due to the hindered rotation around the single bonds connecting the aryl groups, which results in four potential configurational isomers(atropisomers). The separation of the four atropisomers was achieved on a derivatized β-cyclodextrin bonded stationary phase. Further investigation showed that low temperature conditions, including sample preparation(-70 °C), sample storage(-70 °C), and chromatographic separation(6 °C), were critical to preventing interconversion. LC-UV-laser polarimetric analysis identified peaks 1 and 2 as a pair of enantiomers and peaks3 and 4 as another. Thermodynamic analysis of the retention data indicated that the separation of the pairs of enantiomers is primarily enthalpy controlled as indicated by the positive slope of the van't Huff plot. The difference in absolute Δ(Δ H), ranged from 2.20 k J/mol to 2.42 k J/mol.

关键词： Atropisomer separation Chiral HpLC Thermodynamic parameters β-cyclodextrin stationary phase Chiral separation mechanism

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Cryogenic wedges on the NE Qinghai-Tibet and Ordos plateaus:Their characteristics,origin and OSL dating

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Research in Cold and Arid Regions 2021年第6期13卷 463-473页

作者： Stuart A.harris Department of Geography University of CalgaryCalgaryAlbertaT2N 1N4Canada

Cryogenic wedges developed due to very cold,rather arid conditions during the maximum of the last cold event when the drying up of the neighboring China Sea resulted in the failure of the East Asian *** the climate ameliorated and the Monsoon rains reappeared,ice-wedges *** warming permitted thawing of the ice infillings accompanied by replacement of the ice by sediments partly from the host ground as well as from the surface by wind or sheet *** cases of extreme surface water flow on slopes after 10 ka B.p.,small baydjarakhs typically c.50 cm high developed,only to have the resulting hollows infilled by sediments carried by wind and/or sheet *** shallow structures form a network on top of many of the cryogenic *** complex history makes dating the ages of the wedges difficult using OSL ***,past field work ignored the problem of the angle of the cut face to the direction of the wedge infilling when sampling the contents of the narrow wedges,resulting in potential contamination of the samples with the host *** of the larger deposits should be alright,but the likelihood of contamination makes the interpretation of the resulting OSL dates from the narrow wedges *** wedges consisting of primary mineral infillings should still have similar OSL dates with depth for a given wedge,but the distinction between ice-wedge infillings and soil wedges is difficult since both can exhibit older dates of the infillings with *** available data suggests that ice-wedges were significantly more common than sediment-filled primary wedges.A protocol to avoid having to obtain large numbers of OSL dates by more careful field sampling and the use of grain size determinations is provided in the Appendix.

关键词： cryogenic wedges OSL dating NE Qinghai-Tibet plateau differentiation of primary and secondary wedges baydjarakhs in arid climates

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