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Drugging SUmOylation for neuroprotection and oncotherapy

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Neural Regeneration Research 2018年第3期13卷 415-416页

作者： Joshua D. Bernstock Daniel G. Ye Yang-ja Lee Florian Gessler gregory K. Friedman Wei Zheng John m. Hallenbeck Stroke Branch National Institute of Neurological Disorders and Stroke National institutes of Health (NINDS/NIH) Bethesda MD USA Department of Clinical Neurosciences - Division of Stem Cell Neurobiology Wellcome Trust-Medical Research Council Stem Cell Institute and NIHR Biomedical Research Centre University of Cambridge UK Department of Pediatrics Division of Pediatric Hematology and Oncology University of Alabama at Birmingham Birmingham AL USA National Center for Advancing Translational Sciences National Institutes of Health (NCATS/NIH) Bethesda MD USA

Recently there have been exciting research advances in neuroprotective therapies for ischemic stroke. In the past, the search for neu- roprotective agents has been fraught with failure at the clinical trials stage due to numerous factors, including subject heterogeneity and improper therapeutic windows （Tymianski, 2017）. moreover, it is becoming clearer that the complex and evolving pathobiology of stroke requires multimodal therapeutic approaches capable of modulating the numerous axes that contribute to ischemia/reperfusion damage, rather than targeting a single axis （Bernstock et al., 2018a）. With the success of recent endovascular thrombectomy （EVT） trials, it has been suggested that clinical trials of EVT with adjunct neuroprotection can overcome past difficulties and maximize the effect size by using imaging to reduce patient heterogeneity （i. e., selecting those with large vessel occlusions, small ischemic cores, and good collateral circulation）, restoring perfusion using better EVT devices, and enrolling patients in the correct therapeutic window （i.e., when they still have salvageable brain tissue）（Tymianski, 2017）. Considering the opportunity that this represents for new, better clinical trials of neuroprotective agents, the search is on for high-potential compounds that may be investigated in these future studies.

关键词： Drugging SUmOylation for neuroprotection and oncotherapy OGD

Digital earth:yesterday,today,and tomorrow

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International Journal of Digital Earth 2023年第1期16卷 1022-1072页

作者： Alessandro Annoni Stefano Nativi ArzuÇöltekin Cheryl Desha Eugene Eremchenko Caroline m.Gevaert gregory Giuliani min Chen Luis Perez-mora Joseph Strobl Stephanie Tumampos International Society for Digital Earth BeijingPeople’s Republic of China National Research Council RomeItaly University of Applied Sciences and Arts Northwestern Switzerland FHNW School of EngineeringInstitute of Interactive Technologies IITBrugg-WindischSwitzerland Nathan Campus Griffith UniversityCities Research InstituteBrisbaneAustralia Lomonosov moscow State University MoscowRussia Department of Earth Observation Science University of TwenteTwenteThe Netherland Institute for Environmental Sciences/enviroSPACE University of GenevaGenevaSwitzerland Key Laboratory of Virtual Geographic Environment(ministry of Education of PRC) Nanjing Normal UniversityNanjingPeople’s Republic of China Cities Research Institute Nathan CampusGriffith UniversityBrisbaneAustralia Department of Geoinformatics University of SalzburgSalzburgAustria Chair of Remote Sensing Technology Technical University of MunichMunichGermany Big Geospatial Data management Technical University of MunichMunichGermany

The concept of Digital Earth(DE)was formalized by Al Gore in *** that time the technologies needed for its implementation were in an embryonic stage and the concept was quite *** then digital technologies have progressed significantly and their speed and pervasiveness have generated and are still causing the digital transformation of our *** creates new opportunities and challenges for the realization of DE.‘What is DE today?’,‘What could DE be in the future?’,and‘What is needed to make DE a reality?’.To answer these questions it is necessary to examine DE considering all the technological,scientific,social,and economic aspects,but also bearing in mind the principles that inspired its *** understanding the lessons learned from the past,it becomes possible to identify the remaining scientific and technological challenges,and the actions needed to achieve the ultimate goal of a‘Digital Earth for all’.This article reviews the evolution of the DE vision and its multiple definitions,illustrates what has been achieved so far,explains the impact of digital transformation,illustrates the new vision,and concludes with possible future scenarios and recommended actions to facilitate full DE implementation.

关键词： Digital Earth digital transformation sustainable development data governance and ethic citizen empowerment and industry engagement

Critical size limit of biodegradable nanopartides for enhanced lymph node trafficking and paracortex penetration

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Nano Research 2019年第4期12卷 837-844页

作者： gregory P. Howard Garima Verma Xiyu Ke Winter m. Thayer Timothy Hamerly Victoria K. Baxter John E. Lee Rhoel R. Dinglasan Hai-Quan mao Department of Biomedical Engineering Johns Hopkins School of Medicine Baltimore MD 21218 USA Institute for NanoBioTechnology Johns Hopkins University Baltimore MD 2121 & USA W. Harry Feinstone Department of molecular microbiology & Immunology and the Malaria Research Institute Johns Hopkins Bloomberg School of Public Health Baltimore MD 21205 USA Emerging Pathogens Institute Department of Infectious Diseases & Immunology College of Veterinary Medicine University of Florida Gainesville FL 32611 USA Department of materials Science and Engineering Whiting School of Engineering Johns Hopkins University Baltimore MD 21218 USA Johns Hopkins School of Nursing Baltimore MD 21205 USA Department of molecular and Comparative Pathobiology Johns Hopkins School of Medicine Baltimore MD 21205 USA Department of Biomedical Engineering Yale University New Haven CT 06520 USA Translational Tissue Engineering Center Johns Hopkins University School of Medicine Baltimore MD 21231 USA

Lymph node (LN) targeti ng through interstitial drain age of nan oparticles (NPs) is an attractive strategy to stimulate a pote nt immune respo nse, as LNs are the primary site for lymphocyte priming by antigen presenting cells (APCs) and triggering of an adaptive immune response. NP size has been shown to influence the efficiency of LN-targeting and retention after subcutaneous injection. For clinical translation, biodegradable NPs are preferred as carrier for vaccine delivery. However, the selective "size gatem for effective LN-drainage, particularly the kinetics of LN trafficking, is less well defined. This is partly due to the challenge in generating size-controlled NPs from biodegradable polymers in the sub-100-nm range. Here, we report the preparation of three sets of poly(lactic-co-glycolic)-b-poly(ethylene-glycol)(PLGA-b-PEG) NPs with number average diameters of 20-, 40-, and 100-nm and narrow size distributions using flash nanoprecipitation. Using NPs labeled with a near-infrared dye, we showed that 20-nm NPs drain rapidly across proximal and distal LNs following subcutaneous inoculation in mice and are retai ned in LNs more effectively than NPs with a nu mber average diameter of 40-nm. The drain age of 100-nm NPs was n egligible. Furthermore, the 20-nm NPs showed the highest degree of penetration around the paracortex region and had enhanced access to dendritic cells in the LNs. Together, these data confirmed that small, size-controlled PLGA-b-PEG NPs at the lower threshold of about 30-nm are most effective for LN trafficking, retention, and APC uptake after s.c. administration. This report could inform the design of LN-targeted NP carrier for the delivery of therapeutic or prophylactic vaccines.

关键词： biodegradable nano particle lymph node trafficking vaccine delivery nanoparticle size an tigen presenting cells in vivo imaging

Pre-implantation exogenous progesterone and pregnancy in sheep:***,nutrient transport,and progestamedins

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Journal of Animal Science and Biotechnology 2021年第3期12卷 935-951页

作者： Emily C.Hoskins Katherine m.Halloran Claire Stenhouse Robyn m.moses Kathrin A.Dunlap michael C.Satterfield Heewon Seo gregory A.Johnson Guoyao Wu Fuller W.Bazer Departments of Animal Science Texas A&M UniversityCollege StationTX 77843-2471USA Veterinary Integrative Biosciences Texas A&M UniversityCollege StationTX 77843USA

Background:Administration of exogenous progesterone(P4)to ewes during the pre-implantation period advances conceptus development and *** study determined effects of exogenous P4 on transport of select nutrients and pathways that enhance conceptus *** ewes(n=38)were treated with either 25 mg P4 in 1 mL corn oil(P4,n=18)or 1mL corn oil alone(CO,n=20)from day 1.5 through day 8 of pregnancy and hysterectomized on either day 9 or day 12 of *** expression of genes encoding enzymes for synthesis of polyamines,transporters of glucose,arginine,and glycine,as well as progestamedins was determined by ***:On day 12 of pregnancy,conceptuses from P4-treated ewes had elongated while those from CO-treated ewes were *** mRNA expression of AZIN2,an arginine decarboxylase,was lower in endometria of P4-treated than CO-treated ewes on day 9 of *** of FGF10,a progestamedin,was greater in endometria of CO and P4-treated ewes on day 12 of gestation in addition to P4-treated ewes necropsied on day 9 of *** with P4 down-regulated endometrial expression of amino acid transporter SLC1A4 on day 12 of ***:Results indicated that administration of exogenous P4 during the pre-implantation period advanced the expression of FGF10,which may accelerate proliferation of trophectoderm cells,but also was correlated with decreased expression of glycine and serine transporters and polyamine synthesis enzyme *** research with increased sample sizes may determine how differential expression affects endometrial functions and potentially embryonic loss.

关键词： Amino acid Endometrium Gene expression Polyamine Progesterone

Non-invasive delivery of levodopa-loaded nanoparticles to the brain via lymphatic vasculature to enhance treatment of Parkinson’s disease

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Nano Research 2021年第8期14卷 2749-2761页

作者： Tianqi Nie Zhiyu He Jinchang Zhu Kuntao Chen gregory P.Howard Jesus Pacheco-Torres II minn Pengfei Zhao Zaver m.Bhujwalla Hai-Quan mao Lixin Liu Yongming Chen School of materials Science and Engineering Key Laboratory for Polymeric Composite and Functional Materials of Ministry of EducationSun Yat-sen UniversityGuangzhou 510275China Key Laboratory of marine Chemistry Theory and Technology Ministry of EducationOcean University of ChinaQingdao 266100China Department of materials Science and Engineering Johns Hopkins University BaltimoreMD 21218USA Department of Biomedical Engineering Johns Hopkins School of medicine BaltimoreMD 21205USA Institute for NanoBioTechnology Johns Hopkins UniversityBaltimoreMD 21218USA Division of Nuclear medicine and molecular Imaging Department of Radiology and Radiological Science Johns Hopkins School of MedicineBaltimoreMD 21205USA Translational Tissue Engineering Center Johns Hopkins School of MedicineBaltimoreMD 21287USA

Levodopa(L-DOPA),a precursor of dopamine,is commonly prescribed for the treatment of the Parkinson’s disease(PD).However,oral administration of levodopa results in a high level of homocysteine in the peripheral circulation,thereby elevating the risk of cardiovascular disease,and limiting its clinical ***,we report a non-invasive method to deliver levodopa to the brain by delivering L-DOPA-loaded sub-50 nm nanoparticles via brain-lymphatic *** hydrophilic L-DOPA was successfully encapsulated into nanoparticles of tannic acid(TA)/polyvinyl alcohol(PVA)via hydrogen bonding using the flash nanocomplexation(FNC)process,resulting in a high L-DOPA-loading capacity and uniform size in a scalable *** analysis in a PD rat model demonstrated that the levels of dopamine and tyrosine hydroxylase,which indicate the dopaminergic neuron functions,were increased by 2-and 4-fold,*** disorders and cerebral oxidative stress of the rats were significantly *** formulation exhibited a high degree of biocompatibility as evidenced by lack of induced inflammation or other pathological changes in major *** antioxidative and drug-delivery platform administered through the brain-lymphatic vasculature shows promise for clinical treatment of the PD.

关键词： levodopa brain delivery cerebral lymphatic vasculature Parkinson’s disease

Process-Based Friction Factor for Pipe Flow

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Open Journal of Fluid Dynamics 2017年第2期7卷 219-230页

作者： James m. gregory John A. mcEnery Professor Emeritus Civil Engineering Department Texas Tech University Lubbock Texas USA mcEnery Water Resources LLC Arlington Texas USA

The moody Diagram is widely used to determine the friction factor for fluid flow in pipes. The diagram combines the effects of Reynolds number and relative roughness to determine the friction factor. The relationship is highly non-linear and appears to have a complex interaction between viscous and boundary roughness effects. The moody Diagram is based on predictions from an equation developed by Colebrook in 1939. The relationship requires an iteration process to make predictions. While empirical relationships have been developed that provide good predictions without an iteration process, no one has fully explained the cause for the observed results. The objective of this paper is to present a logical development for prediction of the friction factor. An equation has been developed that models the summed effect of both the laminar sublayer and the boundary roughness on the fluid profile and the resulting friction factor for pipes. The new equation does not require an iteration procedure to obtain values for the friction factor. Predicted results match well with values generated from Colebrook’s work that is expressed in the moody Diagram. Predictions are within one percent of Colebrook values and generally less than 0.3 percent error from his values. The development provides insight to how processes operating at the boundary cause the friction factor to change.

关键词： Friction Boundary Roughness Turbulence Pipe Flow moody Diagram

Oncogene interactions are required for glioma development and progression as revealed by a tissue specific transgenic mouse model

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Chinese Journal of Cancer 2011年第3期30卷 163-172页

作者： Lynette m. moore Kristen m. Holmes gregory N. Fuller Department of Pathology the University of Texas M. D. Anderson Cancer Center

The aggressive and invasive nature of brain tumors has hampered progress in the design and implementation of efficacious therapies. The recent success of targeted therapies in other tumor types makes this an attractive area for research yet complicating matters is the ability of brain tumors to circumvent the targeted pathways to develop drug resistance. Effective therapies will likely need to target more than one signaling pathway or target multiple nodes within a given pathway. Key to identifying these targets is the elucidation of the driver and passenger molecules within these pathways. Animal models provide a useful tool with many advantages in the study of these pathways. These models provide a means to dissect the critical components of tumorigenesis, as well as serve as agents for preclinical testing. This review focuses on the use of the RCAS/tv-a mouse model of brain tumors and describes their unique ability to provide insight into the role of oncogene cooperation in tumor development and progression.

关键词：转基因小鼠模型癌基因组织特异性神经胶质瘤相互作用靶向治疗脑肿瘤信号通路

CRYOABLATION:APPLICATIONS AND EXPERIENCEIN LIVER

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CRYOABLATION:APPLICATIONS AND EXPERIENCEIN LIVER

A CASE STUDY IN PERCUTANEOUS PULmONARY CRYOABLATION

2000全国肿瘤学术大会

作者： gregory m.Graves University of California at Davis Sutter Cancer CenterSacramentoCaliforniaUSA Associate Professor of Surgery M.D

＜正＞Purpose:Ciyoablation is a targeted therapy with multiple applications in gen- eral *** in cryoablation technologies,coupled with the widespread use of intraoperative ultrasound（IOUS）,have led to a resurgence of interest in the technique in the United *** review our experience with ciyoablation in the treatment of hepatic *** and meth- ods:Equipment:An argon-gas based ciyoablation system[Cryocare,Endo- care,Inc.,Iivine,California,USA]is utilized at our *** to four

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A CASE STUDY IN PERCUTANEOUS PULMONARY CRYOABLATION