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Journal of Cancer Metastasis and Treatment 2019年第1期4卷 18-40页

作者： Reem Ali ALHulais stephen john ralph School of Medical Sciences Griffith University Menzies Health Institute Queensland Gold Coast QLD 4222 Australia

Few studies have reported on the analyses of drugs targeting enriched populations of cancer stem cells (CSCs) as a means for identifying potent anti-CSC agents. This review evaluates recent information on the identification and functions of specific CSC surface markers, with particular emphasis on colorectal cancers and the screening of drugs to eliminate such cells. Many of these CSC markers are found commonly expressed on CSCs from different cancer types as well as embryonic stem cells. These markers are often related to hypoxic activation of the WNT/b-catenin pathway, cyclooxygenase-2/prostaglandin E signalling and their relationship to LGR5. By effectively using drugs that inhibit these pathways to kill the CSC population, or otherwise forcing them out of dormancy into active cell division, cancers should become more susceptible to chemotherapy. Such combinational therapies targeting both CSCs and proliferating tumor cells should greatly improve upon the current basis for treatment.

关键词： Cancer stem cells colorectal cancer markers selective drug targeting

NSAID celecoxib: a potent mitochondrial pro-oxidant cytotoxic agent sensitizing metastatic cancers and cancer stem cells to chemotherapy

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Journal of Cancer Metastasis and Treatment 2018年第1期4卷 571-596页

作者： stephen john ralph Sam Nozuhur Rafael Moreno-Sanchez Sara Rodriguez-Enriquez Rhys Pritchard School of Medical Science Griffith UniversitySouthport 4222Gold CoastAustralia Departmento de Bioquímica Instituto Nacional de CardiologiaTlalpan 14080Mexico

Intermittent hypoxia within tumor microenvironments causes pro-oxidative stress impairing oxidative phos-phorylation(OxPhos)and increases mitochondrial production of reactive oxygen species(ROS).In primary tu-mors this provokes metabolic reprogramming of both tumor cells and cancer stem cells and emergence of highly metastatic cancer *** reprogramming is initiated by activating nuclear respiratory factors and hypoxia-inducible factors in response to changes in oxygen and ROS ***,hypoxia-induced pro-oxidative stress drives invasion and ***,it is also the Achilles’heel of metastatic cancer cells because pro-oxi-dative agents further overload the mitochondria and intracellular milieu with excessive ROS to trigger apoptosis,whereas antioxidant agents promote their survival and tumor *** lies the metastatic tumor cell sensitivity to non-steroidal anti-inflammatory drugs(NSAIDs)and we and others have shown that the NSAID celecoxib exerts powerful pro-oxidative anticancer effects by directly targeting mitochondria to increase ROS production and trigger cancer cell death,including metastatic cancer cells and cancer stem *** review highlights the considerable benefits from appropriate NSAID use in humans against post-diagnosis metastatic tumors and the need to further develop their use as adjuvant therapy for advanced stage metastatic disease where they are already showing significantly improved clinical outcomes.

关键词： Non-steroidal anti-inflammatory drug celecoxib metastasis anticancer mitocans chemosensitizing cancer stem cells therapy

An update on penile reconstruction

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Asian Journal of Andrology 2011年第3期13卷 391-394,511页

作者： Giulio Garaffa Amr Abdel Raheem David john ralph St Peter＇s Andrology and the Institute Of Urology wig 6BJ London UK

Penile reconstruction still represents a formidable challenge for the urologist. In this review, the most recent advances in penile reconstruction after trauma, excision of benign and malignant disease and in patients... 详细信息

关键词： aphallia female-to-male sex reassignment surgery genital lymphoedema lichen sclerosus micropenis penile cancer penile trauma

Sub-dissociative dose ketamine administration for managing pain in the emergency department

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World Journal of Emergency Medicine 2018年第4期9卷 249-255页

作者： Sergey Motov Jefferson Drapkin Antonios Likourezos Joshua Doros ralph Monfort john Marshall Department of Emergency Medicine Maimonides Medical Center

BACKGROUND： We describe our experience of utilizing sub-dissociative dose ketamine （SDK） in managing a variety of acute and chronic painful conditions in the emergency department （ED）. METHODS： A descriptive study was conducted in our ED over a period of seven years （2010-2016） by retrospectively reviewing charts of patients aged 18 and older presenting to the ED with painful complaints and receiving SDK analgesia. Primary data analyses included type of SDK administration （intravenous push [IVP], short-infusion [SI] or continuous infusion [CI]）, dosing, rates of analgesic utilization before and after SDK administration, and adverse effects. RESULTS： Three hundred sixty-two patients were enrolled in the study. Mean ketamine doses given by IVP, St and CI were 26.3 rag, 23.4 rag, and 11.3 rag. The mean duration of CI was 135.87 minutes. The percentage of patients not requiring post-SDK analgesia increased by 16%, 18%, and 37% in IVP, SI and CI groups. Adverse effects were recorded for 13% of patients. CONCLUSION： SDK administered by IVP, SI, and CI in the ED for a variety of painful conditions is a feasible analgesic modality in the ED that is associated with a decrease in overall requirements of post-ketamine analgesia and opioid sparing.

关键词： Ketamine Analgesia Emergency department Sub-dissociative Infusion

Characterizing drought in California:new drought indices and scenario-testing in support of resource management

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Ecological Processes 2018年第1期7卷 1-13页

作者： Lorraine E.Flint Alan L.Flint john Mendoza Julie Kalansky F.M.ralph U.S.Geological Survey 6000 J.StSacramentoCA 95819USA Sonoma County Water Agency 404 Aviation Dr.Santa RosaCA 95403USA Scripps Institution of Oceanography 9500 Gilman Dr.La JollaCA 92093USA

Introduction:California’s recent drought(2012–2016)has implications throughout the state for natural resource management and adaptation planning and has generated many discussions about drought characterization and *** study characterizes drought conditions with two indices describing deficits in natural water supply and increases in landscape stress developed on the basis of water balance modeling,at a fine spatial scale to assess the variation in conditions across the entire state,and provides an in-depth evaluation for the Russian River basin in northern California to address local resource management by developing extreme drought scenarios for consideration in planning and ***:We employed the USGS Basin Characterization Model to characterize drought on the basis of water supply(a measure of recharge plus runoff)and landscape stress(climatic water deficit).These were applied to the state and to the Russian River basin where antecedent soil moisture conditions were evaluated and extreme drought scenarios were developed and run through a water management and reservoir operations model to further explore impacts on water ***:Drought indices indicated that as of the end of water year 2016 when reservoirs were full,additional water supply and landscape replenishment of up to three average years of precipitation in some locations was needed to return to normal *** soil conditions in the Russian River were determined to contribute to very different water supply results for different years and were necessary to understand to anticipate proper watershed response to *** drought scenarios manifested very different kinds of drought and recovery and characterization helps to guide the management response to ***:These scenarios and indices illustrate how droughts differ with regard to water supply and landscape stress and how long warm droughts recover much more slowly than short very dry dro

关键词： California drought Russian River Water supply Basin Characterization Model

Identification of Lignin and Polysaccharide Modifications in Populus Wood by Chemometric Analysis of 2D NMR Spectra from Dissolved Cell Walls

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Molecular Plant 2009年第5期2卷 933-942页

作者： Mattias Hedenstrom Susanne Wiklund-Lindstrom Tommy Oman Fachuang Lu Lorenz Gerber Paul Schatz Bjorn Sundberg john ralph Department of Chemistry Umea University SE-90187 Umea Sweden Department of Biochemistry and Great Lakes Bioenergy Research Center University of Wisconsin Madison WI 53706 USA Umea Plant Science Centre Department of Forest Genetics and Plant Physiology Swedish University of Agricultural Sciences SE-90183 Umea Sweden US Dairy Forage Research Center USDA-Agricultural Research Service Madison WI 53706 USA

2D ^13C-^1H HSQC NMR spectroscopy of acetylated cell walls in solution gives a detailed fingerprint that can be used to assess the chemical composition of the complete wall without extensive degradation. We demonstrate how multivariate analysis of such spectra can be used to visualize cell wall changes between sample types as high-resolution 2D NMR loading spectra. Changes in composition and structure for both lignin and polysaccharides can subsequently be interpreted on a molecular level. The multivariate approach alleviates problems associated with peak picking of overlapping peaks, and it allows the deduction of the relative importance of each peak for sample discrimination. As a first proof of concept, we compare Populus tension wood to normal wood. All well established differences in cellulose, hemicellulose, and lignin compositions between these wood types were readily detected, confirming the reliability of the multivariate approach, In a second example, wood from transgenic Populus modified in their degree of pectin methylesterification was compared to that of wild-type trees. We show that differences in both lignin and polysaccharide composition that are difficult to detect with traditional spectral analysis and that could not be a priori predicted were revealed by the multivariate approach. 2D NMR of dissolved cell wall samples combined with multivariate analysis constitutes a novel approach in cell wall analysis and provides a new tool that will benefit cell wall research.

关键词： Aspen biostatistics cell walls multivariate data analysis NMR spectroscopy tension wood

PagMYB128 regulates secondary cell wall formation by direct activation of cell wall biosynthetic genes during wood formation in poplar

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Journal of Integrative Plant Biology 2024年第8期66卷 1658-1674页

作者： Yuanyuan Hao Fachuang Lu Seung-Won Pyo Min-Ha Kim Jae-Heung Ko Xiaojing Yan john ralph Quanzi Li State Key Laboratory of Tree Genetics and Breeding Chinese Academy of ForestryBeijing 100091China Department of Biochemistry and DOE Great Lakes Bioenergy Research Center Wisconsin Energy InstituteUniversity of Wisconsin-MadisonWisconsin 53726USA Department of Plant&Environmental New Resources Kyung Hee UniversityYongin 17104Korea

The biosynthesis of cellulose,lignin,and hemicelluloses in plant secondary cell walls(SCWs)is regulated by a hierarchical transcriptional regulatory *** network features orthologous transcription factors shared between poplar and Arabidopsis,highlighting a foundational similarity in their genetic ***,knowledge on the discrepant behavior of the transcriptional-level molecular regulatory mechanisms between poplar and Arabidopsis remains *** this study,we investigated the function of PagMYB128 during wood formation and found it had broader impacts on SCW formation compared to its Arabidopsis ortholog,*** poplar trees overexpressing PagMYB128 exhibited significantly enhanced xylem development,with fiber cells and vessels displaying thicker walls,and an increase in the levels of cellulose,lignin,and hemicelluloses in the *** contrast,plants with dominant repression of PagMYB128 demonstrated the opposite *** sequencing and reverse transcription–quantitative polymerase chain reaction showed that PagMYB128 could activate SCW biosynthetic gene expression,and chromatin immunoprecipitation along with yeast one-hybrid,and effector–reporter assays showed this regulation was *** analysis revealed that PagSND1(SECONDARY WALL-ASSOCIATED NAC-DOMAIN PROTEIN1)directly regulates PagMYB128 but not cell wall metabolic genes,highlighting the pivotal role of PagMYB128 in the SND1-driven regulatory network for wood development,thereby creating a feedforward loop in SCW biosynthesis.

关键词： cellulose hemicellulose lignin PagMYB128 Populus transcription factor wood formation

Confucian Political Philosophy for Non-Confucians

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Frontiers of Philosophy in China 2015年第4期10卷 547-567页

作者： ralph Weber Institute for European Global Studies University of Basel Gellertstrasse 27 4020 BaselSwitzerland

Contemporary proponents of Confucian political philosophy often ignore the fact that any sizeable future Confucian political order will have to accommodate many “non-Confucians.” The guiding question of this paper is therefore the following: how could a Confucian political philosophy, if it can at all, adequately take into account a plurality of comprehensive worldviews? I first turn to john Rawls and his account of these terms and of reasonable pluralism more generally. I then examine some particularly relevant developments and criticism of Rawls’ account. Finally, I offer a discussion of some recent proposals for a Confucian political philosophy, and examine to what extent each recognizes the fact of pluralism, sees it as a challenge, and deals with it in a persuasive manner. The paper concludes with a depiction of two major stumbling blocks that might stand firmly in the way of such a pluralism-accommodating political Confucianism.

关键词： Confucian political philosophy liberal democracy pluralism comprehensive worldviews john Rawls

Entropy generation in bypass transitional boundary layer flows

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Journal of Hydrodynamics 2014年第5期26卷 669-680页

作者： GEORGE Joseph OWEN Landon D. XING Tao MCELIGOT Donald M. CREPEAU john C. BUDWIG ralph S. NOLAN Kevin P. Department of Mechanical Engineering College of EngineeringUniversity of IdahoMoscowIdaho 83843USA University of Idaho Idaho FallsIdaho 83402USA University of Idaho BoiseIdaho 83702USA Imperial College London London SW7-28ZUK

The primary objective of this study is to evaluate the accuracy of using computational fluid dynamics （CFD） turbulence models to predict entropy generation rates in bypass transitional boundary layers flows under zero and adverse pressure gradients. Entropy generation rates in such flows are evaluated employing the commercial CFD software, ANSYS FLUENT. Various turbulence and transitional models are assessed by comparing their results with the direct numerical simulation （DNS） data and two recent CFD studies. A solution verification study is conducted on three systematically refined meshes. The factor of safety method is used to estimate the numerical error and grid uncertainties. Monotonic convergence is achieved for all simulations. The Reynolds number based on momentum thickness, Reo, skin-friction coefficient, Cf, approximate entropy generation rates, S, dissipation coefficient, Cd , and the intermittency, y, are calculated for bypass transition simulations. All Reynolds averaged Navier-Stokes （RANS） turbulence and transitional models show improvement over previous CFD results in predicting onset of transition. The transition SST k - ω 4 equation model shows closest agreement with DNS data for all flow conditions in this study due to a much finer grid and more accurate inlet boundary conditions. The other RANS models predict an early onset of transition and higher boundary layer entropy generation rates than the DNS shows.

关键词： entropy generation bypass transition Reynolds averaged Navier-Stokes (RANS) transitional boundary layer turbulence models

Near-Surface Wind-Speed Stilling in Alaska during 1984-2016 and Its Impact on the Sustainability of Wind Power

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Journal of Power and Energy Engineering 2019年第7期7卷 71-124页

作者： Gerhard Kramm Nicole Molders john Cooney ralph Dlugi Engineering Meteorology Consulting Fairbanks AK USA Department of Atmospheric Sciences and Geophysical Institute University of Alaska Fairbanks Fairbanks AK USA Department of Atmospheric Sciences Texas A&M University College Station TX USA Arbeitsgruppe Atmospharische Prozesse (AGAP) Munich Germany

Based on wind-speed records of Alaska’s 19 first-order weather stations, we analyzed the near-surface wind-speed stilling for January 1, 1984 to December 31, 2016. With exception of Big Delta that indicates an increase of 0.0157 m·s–1·a–1, on average, all other first-order weather stations show declining trends in the near-surface wind speeds. In most cases, the average trends are less then?–0.0300?m·s–1·a–1. The strongest average trend of?–0.0500?m·s–1·a–1 occurred at Homer, followed by?–0.0492?m·s–1·a–1 at Bettles, and?–0.0453?m·s–1·a–1 at Yakutat, while the declining trend at Barrow is marginal. The impact of the near-surface wind-speed stilling on the wind-power potential expressed by the wind-power density was predicted and compared with the wind-power classification of the National Renewable Energy Laboratory and the Alaska Energy Authority. This wind-power potential is, however, of subordinate importance because wind turbines only extract a fraction of the kinetic energy from the wind field characterized by the power efficiency. Since wind turbine technology has notably improved during the past 35 years, we hypothetically used seven currently available wind turbines of different rated power and three different shear exponents to assess the wind-power sustainability under changing wind regimes. The shear exponents 1/10, 1/7, and 1/5 served to examine the range of wind power for various conditions of thermal stratification. Based on our analysis for January 1, 1984 to December 31, 2016, Cold Bay, St. Paul Island, Kotzebue, and Bethel would be very good candidates for wind farms. To quantify the impact of a changing wind regime on wind-power sustainability, we predicted wind power for the periods January 1, 1984 to December 31, 1994 and January 1, 2006 to December 31, 2016 as well. Besides Big Delta that suggests an increase in wind power of up to 12% for 1/7, predicted wind power decreased at all sites with the highest decline at Annette (≈38%), Kodiak (≈30%),

关键词： Near-Surface Wind Speed Wind Power Wind-Power Potential Wind-Power Density Wind-Speed Stilling Energy Flux Budget Sensible and Latent Heat