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Identification of Global DNA Methylation Signatures in Glioblastoma-Derived cancer Stem cells

Journal of Genetics and Genomics 2015年第7期42卷 355-371页

作者： Eun-Joon Lee Prakash Rath Jimei Liu Dungsung Ryu Lirong Pei Satish K.Noonepalle Austin Y.Shull Qi Feng N.Scott Litofsky douglas c.Miller douglas c.anthony Mark D.Kirk John Laterra Libin Deng Hong-Bo Xin Xinguo Wang Jeong-Hyeon choi Huidong Shi GRU cancer center Georgia Regents University Department of Biology College of Art and SciencesUniversity of Missouri Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological HealthFood and Drug Administration Department of Biochemistry and Molecular Biology Georgia Regents University Division of Neurological Surgery University of Missouri School of Medicine Department of Pathology and Anatomical Sciences University of Missouri School of Medicine Department of Pathology and Laboratory Medicine Brown University and Lifespan Academic Medical Center Department of Neurology The Hugo W.Moser Research Institute at Kennedy Krieger Inc.and The Johns Hopkins University School of Medicine Institute of Translational Medicine Nanchang University David H.Murdock Research Institute Department of Biostatistics and Epidemiology Georgia Regents University

Glioblastoma （GBM） is the most common and most aggressive primary brain tumor in adults. The existence of a small population of stem-like tumor cells that efficiently propagate tumors and resist cytotoxic therapy is one proposed mechanism leading to the resilient behavior of tumor cells and poor prognosis. In this study, we performed an in-depth analysis of the DNA methylation landscape in GBM- derived cancer stem ceils （GScs）. Parallel comparisons of primary tumors and GSc lines derived from these tumors with normal controls （a neural stem cell （NSc） line and normal brain tissue） identified groups of hyper- and hypomethylated genes that display a trend of either increasing or decreasing methylation levels in the order of controls, primary GBMs, and their counterpart GSc lines, respectively. Interestingly, concurrent promoter hypermethylation and gene body hypomethylation were observed in a subset of genes including MGMT, AJAP1 and PTPRN2. These unique DNA methylation signatures were also found in primary GBM-derived xenograft tumors indicating that they are not tissue culture-related epigenetic changes. Integration of GSc-specific epigenetic signatures with gene expression analysis further identified candidate tumor suppressor genes that are frequently down-regulated in GBMs such as SPINT2, NEFM and PENK. Forced re-expression of SPINT2 reduced glioma cell proliferative capacity, anchorage independent growth, cell motility, and tumor sphere formation in vitro. The results from this study demonstrate that GScs possess unique epigenetic signatures that may play important roles in the pathogenesis of GBM.

关键词： Glioblastoma cancer stem cells DNA methylation SPINT2

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Impact of vasculature damage on the outcome of spinal cord injury:a novel collagenase-induced model may give new insights into the mechanisms involved

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Neural Regeneration Research 2014年第20期9卷 1783-1786页

作者： Patrick Losey Daniel c.anthony Experimental Neuropathology Department of PharmacologyUniversity of OxfordOxfordUK

The deleterious effect of vasculature damage on the outcome of spinal cord injury has long been recognized, and numerous clinical studies have shown that the presence of hemorrhage into the spinal cord is directly associated with a poorer neurological outcome. Vascular damage leads to de- creased blood flow to the cord and the release of potentially toxic blood-borne components. Here we consider the mechanisms that may be contributing to hemorrhage-induced damage and discuss the utility of a new model of spinal cord hemorrhage, which was urgently required as most of our current understanding has been extrapolated from intracerebral hemorrhage studies.

关键词： spinal cord injury vasculature hemorrhage animal model collagenase stereotaxic microinjection

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Potential distributional shifts in North America of allelopathic invasive plant species under climate change models

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Plant Diversity 2022年第1期44卷 11-19页

作者： Anson Wang anthony E.Melton douglas ESoltis Pamela SSoltis Department of Biology University of FloridaGainesvilleFL32611USA Florida Museum of Natural History University of FloridaGainesvilleFL32611USA Genetics Institute University of FloridaGainesvilleFL32610USA Biodiversity Institute University of FloridaGainesvilleFL32611USA

Predictive studies play a crucial role in the study of biological invasions of terrestrial plants under possible climate change *** species are recognized for their ability to modify soil microbial communities and influence ecosystem ***,we focused on six species of allelopathic flowering plants-Ailanthus altissima,casuarina equisetifolia,centaurea stoebe ***,Dioscorea bulbifera,Lantana camara,and Schinus terebinthifolia-Xhat are invasive in North America and examined their potential to spread further during projected climate *** used Species Distribution Models(SDMs)to predict future suitable areas for these species in North America under several proposed future climate *** and Maxent were used to develop SDMs,estimate current distributions,and predict future areas of suitable climate for each *** with the greatest predicted suitable climate in the future include the northeastern and the coastal northwestern regions of North *** size estimations demonstrate the possibility of extreme range loss for these invasives in the southeastern United States,while new areas may become suitable in the northeastern United States and southeastern *** findings show an overall northward shift of suitable climate during the next few decades,given projected changes in temperature and *** results can be utilized to analyze potential shifts in the distribution of these invasive species and may aid in the development of conservation and management plans to target and control dissemination in areas at higher risk for potential future invasion by these allelopathic species.

关键词： Allelopathy Invasive species Species distribution models Ecological niche models Invasion impacts Multi-species assessment

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Risk Management——An Industry Approach

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Biomedical and Environmental Sciences 2001年第1期14卷 21-29页

作者： anthony c. HUGGETT Regional Quality Assurance Laboratory

An effective risk management system covering the whole process of food production from “farm to fork” is required by the food industry in order to assure that the food provided to consumers is safe. Food safety and quality assurance begins with the design and development of food products starting with product conceptualisation and continuing with the selection, purchasing, and evaluation of raw materials and with the specifications for processing, packaging and distribution. Within a larger quality management framework a number of tools have been developed by the food industry, which when used in an integrated fashion facilitate the management of food safety. These include good manufacturing practice (GMP), good hygiene practice (GHP) and HAccP (hazard analysis critical control point) as well as quality systems which allow the verification that all factors affecting the safety of a product are under control. Finally, regulations and systems can only function if they are applied. Everyone, from the farmer, the line operator in the manufacturing plant, to the person handling the food in distribution and sales, needs to be aware of his influence with regards safety. The effectiveness of safety awareness programs specific to each area is key to an industry approach to risk management.

关键词： Food Industry Risk Management Agriculture Food contamination Food Handling Humans Public Health Public Policy Quality control Risk Assessment Safety

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Powering brain power: GLUT1 and the era of structure based human transporter biology

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National Science Review 2015年第1期2卷 3-4页

作者： douglas c.Rees chemistry and chemical Engineering Howard Hughes Medical InstituteCalifornia Institute of Technology

Every student of biochemistry quickly appreciates the central role of glycolysis in cellular *** is not usually addressed in an introductory course is how glucose gets inside a cell in the irst *** integral membrane p... 详细信息

关键词： GLUT1 and the era of structure based human transporter biology Powering brain power

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Multivariate adaptive regression splines and neural network models for prediction of pile drivability

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Geoscience Frontiers 2016年第1期7卷 45-52页

作者： Wengang Zhang anthony T.c.Goh School of civil and Environmental Engineering Nanyang Technological UniversitySingapore 639798Singapore

Piles are long, slender structural elements used to transfer the loads from the superstructure through weak strata onto stiffer soils or rocks. For driven piles, the impact of the piling hammer induces compression and tension stresses in the piles. Hence, an important design consideration is to check that the strength of the pile is sufficient to resist the stresses caused by the impact of the pile hammer. Due to its complexity, pile drivability lacks a precise analytical solution with regard to the phenomena *** situations where measured data or numerical hypothetical results are available, neural networks stand out in mapping the nonlinear interactions and relationships between the system’s predictors and dependent responses. In addition, unlike most computational tools, no mathematical relationship assumption between the dependent and independent variables has to be made. Nevertheless, neural networks have been criticized for their long trial-and-error training process since the optimal configuration is not known a priori. This paper investigates the use of a fairly simple nonparametric regression algorithm known as multivariate adaptive regression splines（MARS）, as an alternative to neural networks, to approximate the relationship between the inputs and dependent response, and to mathematically interpret the relationship between the various parameters. In this paper, the Back propagation neural network（BPNN） and MARS models are developed for assessing pile drivability in relation to the prediction of the Maximum compressive stresses（McS）, Maximum tensile stresses（MTS）, and Blow per foot（BPF）. A database of more than four thousand piles is utilized for model development and comparative performance between BPNN and MARS predictions.

关键词： Back propagation neural network Multivariate adaptive regression splines Pile drivability computational efficiency Nonlinearity

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Hadron resonances as rovibrational states

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chinese Physics c 2021年第8期45卷 99-104页

作者： douglas L.Bernardo cristiano c.Bastos Antonio c.Pavao Departamento de Quimica Fundamental Universidade Federal de PernambucoRecife50740-540Brazil Departamento de Quimica Universidade Federal Rural de PernambucoRecife52171-900Brazil

A rovibrational model,including anharmonic,centrifugal,and coriolis corrections,is used to calculate π,K,N,and ∑ orbital and radial *** four orbital excitations of the n meson correspond to the/?(1235),ti2(1670),63(2030),and π4(2250)*** first four radial excitations correspond to the π(1300),π(1800),π(2070),and 7t(2360)*** orbital excitations of the K meson are interpreted as the K_(1)(1270),K_(2)(1770),K_(3)(2320),and K_(4)(2500)resonances;its radial excitations correspond to the K(1460)and K(1830)*** N orbital excitations are identified with the N(1520),N(1680),N(2190),N(2220),and N(2600)*** first four radial excitations of the N family correspond to the N(1440),N(1880),N(2100),and N(2300)*** orbital excitations of the ∑ baryon are associated with the ∑(1670),∑(1915),∑(2100),and ∑(2250)resonances,whereas its radial excitations are identified with the ∑(1660),∑(1770),and ∑(1880)*** proposed rovibrational model calculations show a good agreement with the corresponding experimental values and allow for the prediction of hadron resonances,thereby proving to be useful for the interpretation of excited hadron spectra.

关键词： excited hadron spectrum orbital and radial resonances rovibrational states

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Forest composition and red oak (Quercus sp.) response to elevation gradients across greentree reservoirs

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Forest Ecosystems 2023年第5期10卷 607-617页

作者： cassandra Hug Pradip Saud Keith McKnight douglas c.Osborne college of Forestry Agriculturaland Natural ResourcesUniversity of Arkansas at MonticelloMonticelloAR71656USA USFWS/Lower Mississippi Valley Joint Venture TylerTX75707USA Five Oaks Ag Research and Education center HumphreyAR72073USA

Elevation gradients within forested wetlands have long been recognized for their role in defining species composition through factors such as hydrology and soil *** reservoirs(GTRs)are leveeimpounded tracts of bottomland hardwood forest flooded throughout the winter months to provide habitat for overwintering *** flooding of GTRs alters the forest composition due to flood frequency,depth,and duration in combination with slight changes in *** evaluate the effect of elevation gradients,soil properties,and management techniques in the overstory species composition and red oak(Quercus spp.)species abundance,we inventoried 662 plots across 12 independent GTRs in eastern *** the lower elevations ranging from 50.98 to 54.99 m above sea level,the importance value index(IVI)was highest for nuttall oak(Quercus texana)and overcup oak(Quercus lyrata),whereas IVI shifted to cherrybark oak(Quercus pagoda)in the higher elevations ranging from 54.99 to 58.00 *** diversity did not differ by elevation gradient,soil property,or management technique within *** diversity,using non-metric multi-dimensional scaling(NMDS)analysis,indicated site-specific variability significantly correlated with the environmental predictors,including elevation(R^(2)=0.57),easting(R^(2)=0.47),soil texture(R^(2)=0.21),and pH(R^(2)=0.12).Red oak species-specific mixed-effects modeling of abundance response using Poisson distribution suggested an inverse correlation of nuttall oak and a direct correlation of cherrybark oak abundance with ***,willow oak(Quercus phellos)abundance was not significantly affected by elevation but was by silt loam soil texture and restoration management *** findings will aid management efforts to reduce the dominance of less desirable species that are prominent under specific environmental conditions and promote the dominance of more desirable *** GTR sustainability is increas

关键词： Bottomland hardwoods Diversity Forested wetland Overstory Red oak Soil Thinning and management

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Effects of the mass and volume shrinkage of ground chip and pellet particles on drying rates

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Particuology 2018年第3期16卷 1-9页

作者： Hamid Rezaei Shahab Sokhansaj c. Jim Lim anthony Lau Xiaotao Bi chemical and Biological Engineering Department University of British Columbia Vancouver BC V6T 1Z3 Canada Environmental Science Division Oak Ridge National Laboratory Oak Ridge TN 37381 USA

The effects of varying the mass and volume of ground chip and pellet particles on the particle drying rate were analyzed. Samples of whole pellets and chips were hammer milled using a 3.2 mm screen and the ground chip and pellet particles were found to have similar size distributions, although the pellet particles were denser and more spherical than the chip particles. Prior to drying, water was added to the particles to obtain 0.10, 0.30, 0.50, 0.70, and 0.90 moisture contents （on a dry mass basis）. The moistened particles were subsequently dried in a constant temperature thin layer dryer set at 50,100, 150, or 200 ~c under dry pure nitrogen, dry compressed air, or atmospheric air. The chip and pellet particles exhibited similar degrees of shrinkage, but the pellet particles underwent a greater reduction in their bulk volume during drying. It appears that the more spherical pellet particles are prone to shrinkage in more than one direction, whereas the needle-like chip particle shrink only in one direction. A variable radius first order drying model was found to fit the experimental data better than a fixed radius model.

关键词： Moisture loss Particle density Ground chip Ground pellet Particle shrinkage Bulk shrinkage

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Long-term stabilization of stage 4 colon cancer using sodium dichloroacetate therapy

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World Journal of clinical cases 2016年第10期4卷 336-343页

作者： Akbar Khan douglas Andrews Anneke c Blackburn Medicor cancer centres Inc. The John curtin School of Medical Research The Australian National University

Oral dichloroacetate sodium(DcA) has been investigated as a novel metabolic therapy for various cancers since 2007, based on data from Bonnet et al that DcA can trigger apoptosis of human lung, breast and brain cancer cells. Response to therapy in human studies is measured by standard response evaluation criteria for solid tumours definitions, which define "response" by the degree of tumour reduction, or tumour disappearance on imaging. However, Blackburn et al have demonstrated that DcA can also act as a cytostatic agent in vitro and in vivo, without causing apoptosis(programmed cell death). A case is presented in which oral DcA therapy resulted in tumour stabilization of stage 4 colon cancer in a 57 years old female for a period of nearly 4 years, with no serious toxicity. Since the natural history of stage 4 colon cancer consists of steady progression leading to disability and death, this case highlights a novel use of DcA as a cytostatic agent with a potential to maintain long-term stability of advanced-stage cancer.

关键词： Dichloroacetate cancer colon colorectal cytostatic Stabilization Growth inhibition Intravenous

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