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Inhibition of Wnt signaling by Frizzled7 antibody-coated nanoshells sensitizes triple-negative breast cancer cells to the autophagy regulator chloroquine

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Nano Research 2020年第6期13卷 1693-1703页

作者： Jianxin Wang megan N.Dang Emily S.Day Department of Biomedical Engineering University of DelawareNewarkDE19716USA Department of Materials Science and Engineering University of DelawareNewarkDE19716USA Helen F.Graham Cancer Center&Research Institute NewarkDE19713USA

Nano Research volume 13,pages1693–1703(2020)Cite this article 137 Accesses 6 Altmetric Metrics details Abstract Despite improvements in our understanding of the biology behind triple-negative breast cancer(TNBC),it remains a devastating disease due to lack of an effective targeted *** Wnt signaling is a promising strategy to combat TNBC because Wnt signaling drives TNBC progression,chemoresistance,and ***,Wnt inhibition can lead to upregulation of autophagy,which confers therapeutic *** provides an opportunity for combination therapy,as autophagy inhibitors applied concurrently with Wnt inhibitors could increase treatment ***,we applied the autophagy inhibitor chloroquine(CQ)to TNBC cells in combination with Frizzled7 antibody-coated nanoshells(FZD7-NS)that suppress Wnt signaling by blocking Wnt ligand/FZD7 receptor interactions,and evaluated this dual treatment in *** found that FZD7-NS can inhibit Axin2 and CyclinD1,two targets of canonical Wnt signaling,and increase the expression of LC3,an autophagy *** FZD7-NS and CQ are applied together,they reduce the expression of several stemness genes in TNBC cells,leading to inhibition of TNBC cell migration and ***,co-delivery of FZD7-NS and CQ is more effective than either therapy alone or the combination of CQ with free FZD7 *** demonstrates that the nanocarrier design is important to its therapeutic ***,these findings indicate that combined regulation of Wnt signaling and autophagy by FZD7-NS and CQ is a promising strategy to combat TNBC.

关键词： nanomedicine nanoparticles combination therapy antibody delivery cancer stem cells

Reducing metal artifacts by restricting negative pixels

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Visual Computing for Industry,Biomedicine,and Art 2021年第1期4卷 142-151页

作者： Gengsheng L.Zeng megan Zeng Department of Computer Science Utah Valley UniversityOremUT 84058USA Department of Radiology and Imaging Sciences University of UtahSalt Lake CityUT 84108USA Department of Electrical Engineering and Computer Science University of California at BerkeleyBerkeleyCA 94720USA

When the object contains metals,its x-ray computed tomography(CT)images are normally affected by streaking *** artifacts are mainly caused by the x-ray beam hardening effects,which deviate the measurements from their true *** interesting observation of the metal artifacts is that certain regions of the metal artifacts often appear as negative pixel *** novel idea in this paper is to set up an objective function that restricts the negative pixel values in the *** must point out that the naïve idea of setting the negative pixel values in the reconstructed image to zero does not give the same *** paper proposes an iterative algorithm to optimize this objective function,and the unknowns are the metal affected *** the metal affected projections are estimated,the filtered backprojection algorithm is used to reconstruct the final *** paper applies the proposed algorithm to some airport bag CT *** bags all contain unknown metallic *** metal artifacts are effectively reduced by the proposed algorithm.

关键词： Filtered backprojection image reconstruction Iterative algorithm Metal artifact reduction Objective function X-ray computed tomography

The immune modifying effects of amino acids on gut-associated lymphoid tissue

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Journal of Animal Science and Biotechnology 2013年第3期4卷 195-204页

作者： megan R Ruth Catherine J Field Department of Agricultural Food and Nutritional Science 4-126A Li Ka Shing Health Research Innovation Centre University of AlbertaEdmonton AB T6G 2E1 Canada

The intestine and the gut-associated lymphoid tissue（GALT） are essential components of whole body immune defense,protecting the body from foreign antigens and pathogens,while allowing tolerance to commensal bacteria and dietary *** requirement for protein to support the immune system is well *** is known regarding the immune modifying properties of individual amino acids,particularly on the *** oral and parenteral feeding studies have established convincing evidence that not only the total protein intake,but the availability of specific dietary amino acids（in particular glutamine,glutamate,and arginine,and perhaps methionine,cysteine and threonine） are essential to optimizing the immune functions of the intestine and the proximal resident immune *** amino acids each have unique properties that include,maintaining the integrity,growth and function of the intestine,as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers,specific T cell functions,and the secretion of IgA by lamina propria *** understanding of this area has come from studies that have supplemented single amino acids to a mixed protein diet and measuring the effect on specific immune *** studies should be designed using amino acid mixtures that target a number of specific functions of GALT in order to optimize immune function in domestic animals and humans during critical periods of development and various disease states.

关键词： Amino acids Arginine Epithelium Glutamate Glutamine Gut-associated lymphoid tissue Intestine Mucosa

Restimate:Recovery Estimation Tool for Resilience Planning

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Journal of Safety Science and Resilience 2024年第1期5卷 47-63页

作者： Scott Miles megan Ly Nick Terry Youngjun Choe Department of Human Centered Design&Engineering Campus Box 352315University of WashingtonSeattleWA 98195United States of America Department of Industrial&Systems Engineering Box 352650University of WashingtonSeattleWA 98195United States of America

The *** Institute of Standards and Technology(NIST)published the Community Resilience Planning Guide in *** NIST Guide advocates for a participatory process for developing a performance measurement framework for the jurisdiction’s resilience against a scenario *** framework centers around tables of expected and desired recovery times for selected community assets,such as electricity,water,and natural gas *** NIST Guide does not provide a method for estimating the expected recovery ***,building high-fidelity computer models for such estimations requires substantial resources that even larger ju-risdictions cannot *** most promising approach to recovery time estimation is to systematically use data elicited from people to tap into the wisdom of the(knowledgeable)*** paper describes a novel research-through-design project to enable the computer-supported elicitation of recovery time series *** work is the first in the literature to examine people’s ability to estimate recovery curves and how design in-fluences such *** main contribution to resilience planning is three-fold:development of a new elicitation tool called Restimate,understanding its potential user base,and providing insights into how it can facilitate resilience *** is the first tool to enable evidence-based expert elicitation in any community with limited resources for resilience *** resilience planning,those who facilitate high-stakes planning activities under large uncertainties(e.g.,mission-critical system design and planning)will benefit from a similar research-through-design process.

关键词： expert elicitation disaster natural hazard infrastructure community resilience restoration user-centered design computer-supported cooperative work

Persistent Precarity and the Disaster of Everyday Life: Homeless People’s Experiences of Natural and Other Hazards

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International Journal of Disaster Risk Science 2019年第3期10卷 332-342页

作者： JC Gaillard Vicky Walters megan Rickerby Yu Shi School of Environment The University of AucklandAuckland 1142New Zealand School of People Environment and PlanningMasseyUniversityAlbany 0632New Zealand Unit for Environmental Sciences and Management North-West UniversityPotchefstroom 2520South Africa

Knowledge of how homeless people deal with natural hazards and disasters is sparse and there is a remarkable absence of homeless people in policies and practices for disaster risk reduction(DRR). This article aims at filling this gap by exploring the lives of homeless people in two New Zealand cities that are exposed to natural hazards. It shows that natural hazards are of marginal concern to homeless people in comparison to the everyday hazards that they experience and that make their everyday life a disaster in itself. The disaster of everyday life is created and compounded by homeless people’s precarious lifeworlds. The article, nonetheless, shows that homeless people’s vulnerability to natural hazards remains high as they lack power to control the processes that shape their everyday lives, to prepare for large-scale events, and to be represented in DRR policy. Therefore, the article ultimately argues that disaster policies require greater attention to be paid to the power structures that create persistent precarity and the ways in which this is experienced in everyday life.

关键词： Everyday life Hazard Homelessness New Zealand Precarity Vulnerability

Advances and controversies in the management of acute cholecystitis in high-risk, critically ill, and unfit-for-surgery patients: the Italian Society of Emergency Surgery and Trauma guidelines

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 724-726页

作者： megan Vidal Vladimir Neychev University of Central Florida College of Medicine OrlandoFLUSA Department of Surgery UCF Lake Nona HospitalUniversity of Central Florida College of MedicineOrlandoFLUSA

There is an ongoing debate about the therapeutic strategies for acute cholecystitis in high-risk,critically ill patients,and finding the optimal management option is a work in *** the recent study“Acute cholecystitis management in high-risk,critically ill,and unfit-for-surgery patients:the Italian Society of Emergency Surgery and Trauma(SICUT)guidelines”,*** et *** current knowledge on treating acute cholecystitis in high risk,critically ill,and unfit for surgery patients(1).The article encompasses topics such as patient stratification,risk factors,and outcomes of non-operative gallbladder drainage and advances the knowledge of the field by proposing specific management recommendations for these patient groups.

关键词： Acute cholecystitis management high-risk patients

The influence of hydrochar from biogas digestate on soil improvement and plant growth aspects

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Biochar 2020年第2期2卷 177-194页

作者： megan de Jager Michael Rohrdanz Luise Giani Carl Von Ossietzky Universitat Institut für Biologie und UmweltwissenschaftenOldenburgGermany

Hydrochar(HC),produced by hydrothermal carbonization,offers technical advantages over biochar(BC)produced by pyrolysis,and is suitable for soil amelioration,carbon sequestration,and enhanced plant *** grain size has been shown to influence nutrient retention,microbial colonization and aggregate formation;however,similar research for HC is *** trials were conducted to investigate the influence of HC grain size[coarse(6.3-2 mm),medium(2-0.63 mm)and fine(50%in all *** effect on NO_(3)^(−)content was indeterminable,while there was little to no effect on biom

关键词： Hydrochar Soil improvement Grain size Plant available nutrients

Identifying diabetes management opportunity areas in the USA

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Family Medicine and Community Health 2020年第1期8卷 53-58页

作者： Michael Topmiller Kyle Shaak Peter J Mallow Autumn M Kieber-emmons Health Landscape LLCCincinnatiOhioUSA Department of Family Medicine Lehigh Valley Health NetworkAllentownPennsylvaniaUSA Health Services Administration Xavier UniversityCincinnatiOhioUSA School of Medicine University of South FloridaTampaFloridaUSA

Using adherence to diabetes management guidelines as a case study,this paper applied a novel geospatial hot-spot and cold-spot methodology to identify priority counties to target *** for this study were obtained from the Dartmouth Atlas of Healthcare,the United States Census Bureau’s American Community Survey and the University of Wisconsin County Health Rankings.A geospatial approach was used to identify four tiers of priority counties for diabetes preventive and management services:diabetes management cold-spots,clusters of counties with low rates of adherence to diabetes preventive and management services(Tier D);Medicare spending hot-spots,clusters of counties with high rates of spending and were diabetes management cold-spots(Tier C);preventable hospitalisation hot-spots,clusters of counties with high rates of spending and are diabetes management cold-spots(Tier B);and counties that were located in a diabetes management cold-spot cluster,preventable hospitalisation hot-spot cluster and Medicare spending hot-spot cluster(Tier A).The four tiers of priority counties were geographically concentrated in Texas and Oklahoma,the Southeast and central *** these tiers,there were 62 Tier A *** of preventable hospitalisations and Medicare spending were higher in Tier A counties compared with national *** same counties had much lower rates of adherence to diabetes preventive and management *** novel geospatial mapping approach used in this study may allow practitioners and policy makers to target interventions in areas that have the highest *** refinement of this approach is necessary before making policy recommendations.

关键词： diabetes policy counties

New therapeutic strategies targeting D1-type dopamine receptors for neuropsychiatric disease

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Frontiers in Biology 2015年第3期10卷 230-238页

作者： Young-Cho Kim Stephanie L. Alberico Eric emmons Nandakumar S. Narayanan Department of Neurology University of Iowa Iowa City IA 52242 USA Aging Mind and Brain Initiative Carver College of Medicine University of Iowa Iowa City IA 52242 USA

The neurotransmitter dopamine acts via two major classes of receptors, Dl-type and D2-type. D1 receptors are highly expressed in the striatum and can also be found in the cerebral cortex. Here we review the role of D1 dopamine signaling in two major domains： L-DOPA-induced dyskinesias in Parkinson＇s disease and cognition in neuropsychiatric disorders. While there are many drugs targeting D2-type receptors, there are no drugs that specifically target D1 receptors. It has been difficult to use selective Dl-receptor agonists for clinical applications due to issues with bioavailability, binding affinity, pharmacological kinetics, and side effects. We propose potential therapies that selectively modulate D1 dopamine signaling by targeting second messengers downstream of D1 receptors, aUosteric modulators, or by making targeted modifications to Dl-receptor machinery. The development of therapies specific to Dl-receptor signaling could be a new frontier in the treatment of neurological and psychiatric disorders.

关键词： D1DR dopamine D1 receptor dyskinesia cognition