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A nano-enhanced vaccine for metastatic melanoma immunotherapy

Cancer Drug Resistance 2022年第3期5卷 829-845页

作者： Katelyn e.Salotto Walter C.Olson Jr Karlyn e.Pollack Anuradha Illendula elishama Michel Sydney Henriques Todd Fox Susan Walker Marya Dunlap-Brown Craig L.Slingluff Jr mark Kester Helena W.Snyde School of engineering and Applied Sciences University of VirginiaVirginiaVA 22904USA Department of Surgery School of MedicineUniversity of VirginiaVirginiaVA 22903USA Department of Dermatology School of MedicineUniversity of VirginiaVirginiaVA 22903USA Department of Pharmacology School of MedicineUniversity of VirginiaVirginiaVA 22903USA University of Virginia nanoSTAR Institute VirginiaVA 22903USA Molecular Immunologic&Translational Sciences(MITS)Core School of MedicineUniversity of VirginiaVirginiaVA 22903USA Department of Materials Science School of Engineering and Applied SciencesUniversity of VirginiaVirginiaVA 22903USA

Aim:Despite the huge advancements in cancer therapies and treatments over the past decade,most patients with metastasized melanoma still die from the *** poor prognosis largely results from resistance to conventional chemotherapies and other cytotoxic *** have previously identified 6 antigenic peptides derived from melanomas that have proven efficacious for activating CD4+T cells in clinical trials for *** aim was to improve pharmacodynamics,pharmacokinetic and toxicological parameters by individually encapsulating each of the 6 melanoma helper peptides within their own immunogenic ***:We modified these liposomes as necessary to account for differences in the peptides’chemical properties,resulting in 3 distinct *** further enhance immunogenicity,we also incorporated KDO2,a TLR4 agonist,into the lipid bilayer of all nanoliposome *** then conducted in vivo imaging studies in mice and ex vivo cell studies from 2 patient samples who both strongly expressed one of the identified ***:We demonstrate that these liposomes,loaded with the different melanoma helper peptides,can be readily mixed together and simultaneously delivered without toxicity in *** liposomes are capable of being diffused to the secondary lymphoid organs very quickly and for at least 6 *** addition,we show that these immunogenic liposomes enhance immune responses to specific peptides ex ***:Lipid-based delivery systems,including nanoliposomes and lipid nanoparticles,have now been validated for pharmacological(small molecules,bioactive lipids)and molecular(mRNA,siRNA)therapeutic ***,the utility of these formulations as cancer vaccines,delivering antigenic peptides,has not yet achieved the same degree of commercial ***,we describe the novel and successful development of a nanoliposome-based cancer vaccine for *** vaccines help to circumvent drug resistance by increasing a

关键词： Nanoliposomes nanoscale drug delivery cancer vaccines metastasized melanoma peptides melanoma drug resistance

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Claudin-11 and occludin are major contributors to Sertoli cell tight junction function, in vitro

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Asian Journal of Andrology 2016年第4期18卷 620-626页

作者： mark J McCabe Caroline FH Foo Marcel e Dinger Peter M Smooker Peter G Stanton Male Fertility Regulation Laboratory Hudson Institute of Medical Research Monash Medical Centre Clayton Victoria 3168 Australia School of Applied Sciences Royal Melbourne Institute of Technology University Bundoora Victoria 3088 Australia Kinghorn Centre for Clinical Genomics Garvan Institute of Medical Research Darlinghurst New South Wales 2010 Australia St Vincent's Clinical School UNSW Sydney New South Wales 2052 Australia.

The Sertoli cell tight junction （T J） is the key component of the blood-testis barrier, where it sequesters developing germ cells undergoing spermatogenesis within the seminiferous tubules. Hormonally regulated claudin-11 is a critical transmembrane protein involved in barrier function and its murine knockout results in infertility. We aimed to assess quantitatively the significance of the contribution of claudin-11 to TJ function, in vitro, using siRNA-mediated gene silencing. We also conducted an analysis of the contribution of occludin, another intrinsic transmembrane protein of the TJ. Silencing of claudin-11 and/or occludin was conducted using siRNA in an immature rat Sertoli cell culture model. Transepithelial electrical resistance was used to assess quantitatively TJ function throughout the culture. Two days after siRNA treatment, cells were fixed for immunocytochemical localization of junction proteins or lyzed for RT-PCR assessment of mRNA expression. Silencing of claudin-11, occludin, or both resulted in significant decreases in TJ function of 55% （P 〈 0.01）, 51% （P 〈 0.01）, and 62% （P 〈 0.01）, respectively. Data were concomitant with significant decreases in mRNA expression and marked reductions in the localization of targeted proteins to the Sertoli cell TJ. We provide quantitative evidence that claudin-11 contributes significantly （P 〈 0.01） to Sertoli cell TJ function in vitro. Interestingly, occludin, which is hormonally regulated but not implicated in infertility until late adulthood, is also a significant （P 〈 0.01） contributor to barrier function. Our data are consistent with in vivo studies that clearly demonstrate a role for these proteins in maintaining normal TJ barrier structure and function.

关键词： blood-testis barrier claudin-11 occludin Sertoli cell tight junction siRNA

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Toward the implementation of a universal angle-based optical indoor positioning system

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Frontiers of Optoelectronics 2018年第2期11卷 116-127页

作者： mark H. BeRGeN Ferdinand S. SCHAAL Richard KLUKAS Julian CHeNG Jonathan e HOLZMAN Faculty of Applied Science University of British Columbia Kelowna BC V1V 1V7 Canada Technical University of Denmark Anker Engelunds Vej 1 Bygning 101A 2800 Kgs. Lyngby Denmark

There is an emerging market today for indoor positioning systems capable of working alongside global navigation satellite systems, such as the global positioning system, in indoor environments. Many systems have been proposed in the literature but all of them have fundamental flaws that hold them back from widescale implementation. We review angle-of-arrival （AOA） and angle-difference- of-arrival （ADOA） optical indoor positioning systems which have been proven to be robust, accurate, and easily implementable. We build an AOA/ADOA optical indoor positioning system out of a simple commercial high-speed camera and white light light emitting diodes （LeDs） which operate over a working area of 1 m3, and compare its performance to other indoor positioning methods. The AOA and ADOA systems achieve positioning with low errors of 1.2 and 3.7 cm, respectively.

关键词： angle-of-arrival (AOA) angle-difference-of-arrival (ADOA) indoor positioning optical positioning

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动态系统理论的概念与技术在生物力学分析中的应用（英文）

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Journal of Sport and Health Science 2016年第1期5卷 3-13页

作者： Richard e.A.van emmerik Scott W.Ducharme Avelino C.Amado Joseph hamill Motor Control Laboratory Department of Kinesiology University of Massachusetts Amherst Amherst MA 01003 USA Biomechanics Laboratories Department of Kinesiology University of Massachusetts Amherst Amherst MA 01003 USA

Traditional biomechanical analyses of human movement are generally derived from linear *** these methods can be useful in many situations,they do not describe behaviors in human systems that are predominately *** this reason,nonlinear analysis methods based on a dynamical systems approach have become more prevalent in recent *** analysis techniques have provided new insights into how systems(1) maintain pattern stability,(2) transition into new states,and(3) are governed by short-and long-term(fractal) correlational processes at different spatio-temporal *** different aspects of system dynamics are typically investigated using concepts related to variability,stability,complexity,and *** purpose of this paper is to compare and contrast these different concepts and demonstrate that,although related,these terms represent fundamentally different aspects of system *** particular,we argue that variability should not uniformly be equated with stability or complexity of *** addition,current dynamic stability measures based on nonlinear analysis methods(such as the finite maximal Lyapunov exponent) can reveal local instabilities in movement dynamics,but the degree to which these local instabilities relate to global postural and gait stability and the ability to resist external perturbations remains to be ***,systematic studies are needed to relate observed reductions in complexity with aging and disease to the adaptive capabilities of the movement system and how complexity changes as a function of different task constraints.

关键词：系统概念技术非线性分析方法系统动力学不稳定性非线性行为自适应能力人体运动

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Improved thromboresistance and analytical performance of intravascular amperometric glucose sensors using optimized nitric oxide release coatings

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Chinese Chemical Letters 2015年第4期26卷 464-468页

作者： Alexander K.Wolf Yu Qin Terry C.Major mark e.Meyerhoff Department of Chemistry University of Michigan Department of Chemistry Nanjing University Department of Surgery University of Michigan

In this work, nitric oxide （NO） release coatings designed for intravenous amperometric glucose sensors are optimized through the use ofa polylactic acid （PLA） layer doped with a lipophilic diazeniumdiolated species that releases NO through a proton-driven mechanism. An elast-eon e2As polyurethane coating is used to both moderate NO release from the sensor surface and increase the sensor＇s linear detection range toward glucose. These sensors were evaluated for thromboresistance and in vivo glucose performance through implantation in rabbit veins. By maintaining NO flux on a similar scale to endogenous endothelial cells, implanted glucose sensors exhibited reduced surface clot formation which enables more accurate quantitative glucose measurements continuously. An in vivo time trace of implanted venous sensors demonstrated glucose values that correlated well with the discrete measurements of blood samples on a benchtop point-of-care sensor-based instrument. The raw measured currents from the implanted glucose sensors over 7 h time periods were converted to glucose concentration through use of both a one-point in vivo calibration and a calibration curve obtained in vitro within a bovine serum solution. Control sensors, assembled without NO release functionality, exhibit distinctive surface clotting over the 7 h in vivo implantation period.

关键词： Nitric oxide release coatingsGlucose sensorsPolylactic acid layerQuantitative glucose measurements

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Heart healthy=prostate healthy： SeLeCT, the symbolic end of preventing prostate cancer via heart unhealthy and over anti-oxidation mechanisms？

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Asian Journal of Andrology 2012年第2期14卷 243-244页

作者： mark A Moyad Department of Urology University of Michigan Medical Center Ann Arbor MI 48109-0330 USA

The Selenium and Vitamin e Cancer Prevention Trial （SeLeCT） randomized over 35 000 men into four groups： high-dose vitamin e （400 IU day-1）, high-dose selenium （200 mcg day-1）, combination of vitamin e and sele... 详细信息

关键词： prostate cancer Heart healthy prostate healthy anti-oxidation

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extrapolating plot-scale CO_(2) and ozone enrichment experimental results to novel conditions and scales using mechanistic modeling

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ecological Processes 2018年第1期7卷 348-367页

作者： eric J.Gustafson mark e.Kubiske Brian R.Miranda Yasutomo Hoshika elena Paoletti Institute for Applied ecosystem Studies Northern Research StationUSDA Forest Service5985 Highway KRhinelanderWIUSA Institute of Sustainable Plant Protection National Council of ResearchVia Madonna del Piano 1050019 Sesto FiorentinoItaly

Introduction:The Aspen-FACe experiment was an 11-year study of the effect of elevated CO_(2) and ozone(alone and in combination)on the growth of model aspen communities(pure aspen,aspen-birch,and aspen-maple)in the field in northern Wisconsin,*** remains about how these short-term plotlevel responses might play out over broader temporal and spatial scales where climate change,competition,succession,and disturbances interact with tree-level *** this study,we used a new physiologybased approach(PneT-Succession v3.1)within the forest landscape model LANDIS-II to extrapolate the FACe results to broader temporal scales(and ultimately to landscape scale)by mechanistically accounting for the globally changing drivers of temperature,precipitation,CO_(2),and *** added novel algorithms to the model to mechanistically simulate the effects of ozone on photosynthesis through ozone-induced impairment of stomatal control(i.e.,stomatal sluggishness)and damage of photosynthetic capacity at the chloroplast ***:We calibrated the model to empirical observations of competitive interactions on the elevated CO_(2) and O_(3) plots of the Aspen-FACe experiment and successfully validated it on the combined factor *** used the validated model to extend the Aspen-FACe experiment for 80 *** only aspen clones competed,we found that clone 271 always dominated,although the ozone-tolerant clone was co-dominant when ozone was *** all treatments,when aspen clone 216 and birch competed,birch was always dominant or co-dominant,and when clone 216 and maple competed,clone 216 was dominant,although maple was able to grow steadily because of its shade *** also predicted long-term competitive outcomes for novel assemblages of taxa under each treatment and discovered that future composition and dominant taxa depend on treatment,and that short-term trends do not always persist in the long ***:We identified the strengths and weakne

关键词： Scaling Global change elevated CO_(2) Ozone pollution Aspen-FACe Forest composition Carbon dynamics Forest landscape modeling LANDIS-II PneT-succession

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Rangeland hillslope lengths:A case study at the Walnut Gulch experimental Watershed,southeastern Arizona

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International Soil and Water Conservation Research 2022年第4期10卷 597-609页

作者： Li Li mark A.Nearing Philip Heilman Mary H.Nichols D.P.Guertin C.J.Williams School of Natural Resources and the environment University of ArizonaTucsonAZ85705USA USDA-Agricultural Research Service Southwest Watershed Research CenterTucsonAZ85719USA

Rangeland hillslopes provide much of the sediment supplied to channel systems and their lengths exert a fundamental constraint on hillslope diffusive ***,information regarding lengths of rangeland hillslopes,and how best to estimate them,is *** this study,three groups of watersheds(10 in total)were selected from the Walnut Gulch experimental Watershed according to their geology,soil and vegetation *** 1 watersheds were at lower elevations dominated by shrubs,Group 3 were at high elevations dominated by grass,and Group 2 were mixed shrub and *** hillslope lengths were calculated from 1 m-resolution DeMs using three methods:a flow routing algorithm,slope-area relationships,and inverted relationship with drainage *** that characterize the current watersheds,including Hack's exponent and coefficient,watershed shape coefficient,channel concavity and steepness,and surface roughness,were quantified and related to hillslope *** shows:(1)estimated hillslope lengths were different for the three methods and between the three groups of watersheds;(2)hillslope lengths that measured from the flow routing algorithm for the ten selected watersheds primarily ranged from 30 to 100 m,with a median value of 63.0 m,which was 20%e50%greater than those derived from slope-area plots or drainage densities;(3)hillslope lengths estimated from the flow routing method were greater in Group 3 watersheds than in Group 2 and then in Group 1 *** attributed these differences in hillslope lengths to the historic epeirogenic pulses,watershed and drainage network morphology,and differences in vegetation characteristics;(4)measured hillslope lengths from the flow routing algorithm were best correlated with hillslope relief,then surface roughness,channel steepness and *** results would benefit the applications of hydrological and erosion models in rangelands.

关键词： Rangeland hillslope Slope length Drainage density Slope-area relationship Hillslope hydrology

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Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging

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Asian Journal of Andrology 2017年第4期19卷 439-443页

作者： Shewei Dou Yan Bai Ankit Shandil Degang Ding Dapeng Shi e mark Haacke Meiyun Wang Department of Radiology Henan Provincial People's Hospital and The People's Hospital of Zhengzhou University Zhengzhou 450003 Henan China Department of Postgraduate education School of International Education Zhengzhou University Zhengzhou 450001 Henan China Department of Urology Henan Provincial People's Hospital and The People's Hospital of Zhengzhou University Zhengzhou 450003 Henan China Department of Radiology Wayne State University Detroit 48202 MI USA Department of Administration Magnetic Resonance Innovations Inc. Detroit 48202 USA.

Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar＇s Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient （P 〈 0.05）. In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient （P 〈 0.05）. Given the high incidence of susceptibility-weighted imaging （SWl） abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging.

关键词： calcification computed tomography diffusion-weighted imaging magnetic resonance imaging prostate cancer susceptibility-weighted imaging

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Novel in-capsule synthesis of metal-organic framework for innovative carbon dioxide capture system

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Green energy & environment 2023年第3期8卷 767-774页

作者： Wei Yu Ming Gao Guanhe Rim Tony G.Feric mark L.Rivers Ammar Alahmed Aqil Jamal Ah-Hyung Alissa Park State Key Laboratory of Clean energy Utilization Zhejiang UniversityHangzhou310027China Lenfest Center for Sustainable energy The Earth InstituteColumbia University918 S.W.Mudd HallMail Code 4711500 W 120th St.New YorkNY10027USA Department of earth and environmental engineering 918 S.W.Mudd HallMail Code 4711500 W 120th St.New YorkNY10027USA Department of Chemical engineering Columbia UniversityNew YorkNY10027USA University of Chicago ChicagoIL60637USA Research and Development Center Saudi AramcoDhahran31311Saudi Arabia

Metal-Organic Frameworks(MOFs)have been developed as solid sorbents for CO_(2) capture applications and their properties can be controlled by tuning the chemical blocks of their crystalline units.A number of MOFs(e.g.,HKUST-1)have been developed but the question remains how to deploy them for gas-solid ***,the direct use of MOFs as nanocrystals would lead to serious problems and ***,for the first time,we report a novel MOF-based hybrid sorbent that is produced via an innovative in-situ microencapsulated *** a custom-made double capillary microfluidic assembly,double emulsions of the MOF precursor solutions and UV-curable silicone shell fluid are ***,HKUST-1 MOF is successfully synthesized within the droplets enclosed in the gas permeable *** developed MOF-bearing microcapsules uniquely allow the deployment of functional nanocrystals without the challenge of handling ultrafine particles,and further,can selectively reject undesired compounds to protect encapsulated MOFs.

关键词： encapsulation Metal-Organic Frameworks(MOFs) Carbon capture In-situ microencapsulated synthesis

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