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experimental design and model reduction in systems biology

Frontiers of electrical and electronic engineering in China 2018年第4期6卷 287-306页

作者： jenny e.jeong Qinwei Zhuang Mark K.Transtrum enlu Zhou Peng Qiu School of electrical and Computer engineering Georgia Institute of TechnologyAtlantaGA 30318USA School of Biological Sciences Georgia Institute of TechnologyAtlantaGA 30318USA Department of Physics and Astronomy Brigham Young UniversityProvoUT 84602USA School of Industrial and Systems engineering Georgia Institute of TechnologyAtlantaGA 30318USA Department of Biomedical engineering Georgia Institute of TechnologyAtlantaGA 30318USA、Emory UniversityAtlanta GA 30322USA

In systems biology, the dynamics of biological networks are often modeled with ordinary differential equations (ODes) that encode interacting components in the systems, resulting in highly complex models. In contrast, the amount of experimentally available data is almost always limited, and insufficient to constrain the parameters. In this situation, parameter estimation is a very challenging problem. To address this challenge, two intuitive approaches are to perform experimental design to generate more data, and to perform model reduction to simplify the model. experimental design and model reduction have been traditionally viewed as two distinct areas, and an extensive literature and excellent reviews exist on each of the two areas. Intriguingly, however, the intrinsic connections between the two areas have not been recognized. experimental design and model reduction are deeply related, and can be considered as one unified framework. There are two recent methods that can tackle both areas, one based on model manifold and the other based on profile likelihood. We use a simple sum-of-two-exponentials example to discuss the concepts and algorithmic details of both methods, and provide Matlab-based code and implementation which are useful resources for the dissemination and adoption of experimental design and model reduction in the biology community. From a geometric perspective, we consider the experimental data as a point in a high-dimensional data space and the mathematical model as a manifold living in this space. Parameter estimation can be viewed as a projection of the data point onto the manifold. By examining the singularity around the projected point on the manifold, we can perform both experimental design and model reduction. experimental design identifies new experiments that expand the manifold and remove the singularity, whereas model reduction identifies the nearest boundary, which is the nearest singularity that suggests an appropriate form of a reduced

关键词： experimental design model reduction model manifold profile likelihood

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Suicide risk in juvenile open angle glaucoma patients

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International Journal of Ophthalmology(english edition) 2024年第10期17卷 1880-1886页

作者： Hye.jeong Seong Sukyoung Jung Sooyeon Choe Department of Ophthalmology Chungnam National University HospitalDaejeon 35015Republic of Korea Department of Ophthalmology Chungnam National University College of MedicineDaejeon 35015Republic of Korea Department of Health Care Policy Research Korea Institute for Health and Social AffairsSejong 30147Republic of Korea

AIM:To investigate the association between juvenile open angle glaucoma(JOAG)and mental health among ***:This study used nationally representative data from the 8th Korea National Health and Nutrition examination Survey(KNHANeS)*** diagnosis followed the International Society of Geographical and epidemiological Ophthalmology criteria based on glaucomatous structural defects,visual field defects,corrected vision,and intraocular *** outcomes,suicidal behaviors,psychiatric counseling,and depression were evaluated through mental health *** ratios(ORs)with 95%confidence intervals(CIs)were estimated using logistic regression models,adjusting for ***:Among 7090 participants,3446 met the inclusion criteria for analysis,and 88(2.6%)were diagnosed with open angle glaucoma(OAG).After adjusting for age,sex,and best-corrected visual acuity(VA),participants with OAG were revealed to have significantly higher odds of suicidal behaviors(i.e.,ideation,planning,or attempts)compared with those without OAG(OR:2.70;95%CI:1.12-6.54;P=0.028).This association remained significant after further adjustments for socioeconomic status,lifestyle factors,and presence of chronic conditions(P=0.031 and 0.035,respectively).However,there was no significant difference for the other two outcomes,psychiatric counseling and *** age-stratified analysis revealed a stronger association between OAG and suicidal behaviors in younger JOAG participants(er OAG participants(≥40y;OR:3.80 vs 2.22;95%CI:0.79-18.22 vs 0.56-8.80,respectively).CONCLUSION:OAG patients show a higher risk of suicidal behaviors than those without glaucoma particularly in JOAG patients.

关键词： glaucoma juvenile open angle glaucoma suicide suicidal behavior

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Impact of inorganic and organic pollutants from a Belgian wastewater treatment plant on adjacent surface and groundwaters

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Frontiers of environmental Science & engineering 2024年第4期18卷 75-90页

作者： Mingyue Luo Yiqi Su Delphine jenny Vandeputte Yuwei Jia Guanlei Li Willy Baeyens Marijke Huysmans Marc elskens Yue Gao Analytical Environmental and Geo-Chemistry Department(AMGC)Vrije Universiteit Brussel(VUB)Pleinlaan 21050 BrusselsBelgium Hydrology and Hydraulic engineering(HYDR) Vrije Universiteit Brussel(VUB)Pleinlaan 21050 BrusselsBelgium

Under the pressure of global droughts and water shortage,it is essential to evolve toward a sustainable and robust water *** possible avenue is the maximum reuse of treated wastewater,but the quality of which determines its ***,inorganic(Cd,Pb,Cr,Ni,Cu,and As)and organic(xenoestrogens and polycyclic aromatic contaminants,PACs)contaminants were monthly monitored in an effluent of the wastewater treatment plant(WWTP),the surrounding surface waters and the local groundwater in *** and particulate concentrations of inorganic contaminants in these water bodies were *** addition,Diffusive Gradients in Thin-films(DGT)was used in situ to obtain bioavailable metal *** the WWTP effluent and surface waters,only Ni exceeds the Annual Average-environmental Quality Standard(AA-eQS),while in the groundwater,dissolved As was the predominant ***,in the surface and effluent waters the highest lability degrees were observed for Cd and *** concentrations of these metal species in the effluent water were lower than in the other water ***-organic pollutants,xenoestrogens and PACs were analyzed by dual estrogen and Aryl hydrocarbon Receptor-Chemical Activated LUciferase gene eXpression(eR&AhR-CALUX)*** the annual averaged(AA)bioequivalent concentration of e2(0.18 ng/L)is below the AA-eQS standard(0.4 ng/L),and the bioequivalent concentration of benzo[a]pyrene never exceeded the maximum admissible concentration(MAC),the reclamation and reuse of treated wastewater for groundwater replenishment and agricultural irrigation should pose no environmental problems,at least in a short-term.

关键词： Metal contaminants DGT Labile metal fractions eRe/AhR-CALUX BeQ Xenoestrogens and polycyclic aromatic contaminants

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Novel fabrication techniques for ultra-thin silicon based flexible electronics

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International Journal of extreme Manufacturing 2024年第4期6卷 116-149页

作者： Ju Young Lee.jeong eun Ju Chanwoo Lee Sang Min Won Ki Jun Yu School of electrical and electronic engineering Yonsei University50 Yonsei-roSeodaemunguSeoul 03722Republic of Korea Department of electrical and Computer engineering Sungkyunkwan UniversitySuwon 16419Republic of Korea YU-Korea Institute of Science and Technology(KIST)Institute Yonsei University50Yonsei-roSeodaemun-guSeoul 03722Republic of Korea

Flexible electronics offer a multitude of advantages,such as flexibility,lightweight property,portability,and high *** unique properties allow for seamless applications to curved and soft surfaces,leading to extensive utilization across a wide range of fields in consumer *** applications,for example,span integrated circuits,solar cells,batteries,wearable devices,bio-implants,soft robotics,and biomimetic ***,flexible electronic devices have been developed using a variety of materials such as organic,carbon-based,and inorganic semiconducting ***(Si)owing to its mature fabrication process,excellent electrical,optical,thermal properties,and cost efficiency,remains a compelling material choice for flexible ***,the research on ultra-thin Si in the context of flexible electronics is studied rigorously *** thinning of Si is crucially important for flexible electronics as it reduces its bending stiffness and the resultant bending strain,thereby enhancing flexibility while preserving its exceptional *** review provides a comprehensive overview of the recent efforts in the fabrication techniques for forming ultra-thin Si using top-down and bottom-up approaches and explores their utilization in flexible electronics and their applications.

关键词： flexible electronics silicon fabrication technique top-down approach bottom-up approach

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Molecular regulation of calcium-sensing receptor(CaSR)-mediated signaling

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Chronic Diseases and Translational Medicine 2024年第3期10卷 167-194页

作者： Li Tian Corey Andrews Qiuyun Yan jenny J.Yang Department of Chemistry Center for Diagnostics and TherapeuticsAdvanced Translational Imaging FacilityGeorgia State UniversityAtlantaGeorgiaUSA

Calcium-sensing receptor(CaSR),a family C G-protein-coupled receptor,plays a crucial role in regulating calcium homeostasis by sensing small concentration changes of extracellular Ca^(2+),Mg^(2+),amino acids(e.g.,L-Trp and L-Phe),small peptides,anions(e.g.,HCO_(3)^(-)and PO_(4)^(3-)),and ***-mediated intracellular Ca^(2+)signaling regulates a diverse set of cellular processes including gene transcription,cell proliferation,differentiation,apoptosis,muscle contraction,and neuronal *** of CaSR with mutations results in diseases such as autosomal dominant hypocalcemia,familial hypocalciuric hypercalcemia,and neonatal severe *** also influences calciotropic disorders,such as osteoporosis,and noncalciotropic disorders,such as cancer,Alzheimer's disease,and pulmonary arterial *** study first reviews recent advances in biochemical and structural determination of the framework of CaSR and its interaction sites with natural ligands,as well as exogenous positive allosteric modulators and negative allosteric *** establishment of the first CaSR protein-protein interactome network revealed 94 novel players involved in protein processing in endoplasmic reticulum,trafficking,cell surface expression,endocytosis,degradation,and signaling *** roles of these proteins in Ca^(2+)-dependent cellular physiological processes and in CaSR-dependent cellular signaling provide new insights into the molecular basis of diseases caused by CaSR mutations and dysregulated CaSR activity caused by its protein interactors and facilitate the design of therapeutic agents that target CaSR and other family C G-protein-coupled receptors.

关键词： calcium signaling calcium-sensing receptor G-protein-coupled receptors structure trafficking

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Systematic Radio Telescope Alignment Using Portable Fringe Projection Profilometry

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Nanomanufacturing and Metrology 2024年第1期7卷 75-85页

作者： Joel Berkson Justin Hyatt Nathan Julicher Byeongjoon jeong Isaac Pimienta Rachel Ball Wyatt ellis Jason Voris Diego Torres‑Barajas Daewook Kim James C.Wyant College of Optical Sciences University of Arizona1630 E.University Blvd.TucsonAZ 85721USA Department of Astronomy at Steward Observatory University of Arizona933 N Cherry Ave.TucsonAZ 85721USA

In 2019,the event Horizon Telescope(eHT)released the first-ever image of a black hole event *** are now aiming for higher angular resolutions of distant targets,like black holes,to understand more about the fundamental laws of gravity that govern our *** achieve this higher resolution and increased sensitivity,larger radio telescopes are needed to operate at higher frequencies and in larger *** like the next-generation Very Large Array(ngVLA)and the Square-Kilometer Array(SKA)require building hundreds of telescopes with diameters greater than 10 ms over the next *** has a twofold *** telescope surfaces need to be more accurate to operate at higher frequencies,and the logistics involved in maintaining a radio telescope need to be simplified to support them properly in large *** of these problems can be solved with improved methods for surface metrology that are faster and more accurate with a higher *** leads to faster and more accurate panel alignment and,therefore,a more productive *** this paper,we present the use of binocular fringe projection profilometry as a solution to this problem and demonstrate it by aligning two panels on a 3-m radio telescope *** measurement takes only 10 min and directly delivers feedback on the tip,tilt,and piston of each panel to create the ideal reflector shape.

关键词： Metrology Fringe projection profilometry Off-axis alignment Radio astronomy Radio antenna

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Gender-and Age-Group Specific Association of Persistent Organic Pollutants(POPs)exposure with Diabetes Mellitus:Korean National environmental Health Survey(KoNeHS)2015−2017

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environment & Health 2024年第5期2卷 322-331页

作者： Inae Lee Min Joo Kim Sohyeon Choi Young Joo Park jeongim Park Gökçe Nur Ayaz Gowoon Lee Yoon Hee Cho Hye Li Jeon Chulwoo Lee Gi jeong Cheon Min Kyong Moon Kyungho Choi Graduate School of Public Health Seoul National UniversitySeoul 08826Republic of Korea Institute of Health and environment Seoul National UniversitySeoul 08826Republic of Korea Department of Internal Medicine Seoul National University College of MedicineSeoul 03080Republic of Korea Seoul National University Hospital Healthcare System Gangnam Center Seoul 06236Republic of Korea Department of environmental Health Sciences Soonchunhyang UniversityAsan 31538Republic of Korea Department of Molecular Medicine and Biopharmaceutical Sciences Graduate School of Convergence Science and TechnologySeoul National UniversitySeoul 08826Republic of Korea Center for environmental Health Sciences Department of Biomedical and Pharmaceutical SciencesUniversity of MontanaMissoulaMontana 59812United States environmental Health Research Division National Institute of Environmental ResearchMinistry of EnvironmentIncheon 22689Republic of Korea Department of Nuclear Medicine Seoul National University College of MedicineSeoul 03080Republic of Korea Division of endocrinology Department of Internal MedicineSeoul National University Boramae Medical CenterSeoul 07061Republic of Korea

exposure to persistent organic pollutants(POPs)has been reported as a potential risk factor for diabetes in ***,effect modifications by sex and age,especially among Asian populations,have seldom been *** the present study,we assessed associations of major POPs exposure including organochlorine pesticides(OCPs),polychlorinated biphenyls(PCBs),and polybrominated diphenyl ethers(PBDes),with diabetes in Korean adults(n=1,295),a subset of the Korean National environmental Health Survey(KoNeHS)Cycle 3(2015−2017).In the adult population,serum levels of dichlorodiphenyltrichloroethanes(DDTs)and PCB167 showed an increased odds ratio(OR)for *** stratified by gender,associations became stronger and more consistent in women:In women,serum levels of OCPs including p,p′-DDT,p,p′-dichlorodiphenyldichloroethylene(p,p′-DDe),andΣOCPs and mono-ortho PCBs,such as PCB118 and PCB157,were significantly associated with *** the male participants,however,no significant positive associations were *** stratified by a cutoff age of 50 years,most studied POPs except PBDes,i.e.,p,p′-DDT,p,p′-DDe,PCB118,PCB157,PCB167,PCB138,and PCB153,showed significant associations with diabetes,in the older *** the younger group,however,no measured POPs showed a significant positive *** of endogenous sex hormones or interaction of POPs on aryl hydrocarbon receptors may partly explain the observed differences by gender and age,although further experimental confirmations should *** findings show that POPs exposure at the current levels is associated with diabetes among general Korean adults,and such associations could be modified by gender and age.

关键词： persistent organic pollutants diabetes age gender toxicity equivalency factor

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Pressure-responsive pH-triggered layer-by-layer coating of paclitaxel-eluting balloon catheters for instant high-dose drug delivery for percutaneous coronary artery intervention

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Nano Research 2024年第10期17卷 9141-9151页

作者： jeong Yu Lee Shonit Nair Sharma Sung-Yu Hong Young-Guk Ko Yangsoo Jang Minjae Do Michael Christopher Stark Qiwen Peng Benjamin Allen Mossburg Bo Chan Seo Yuhan Lee Department of Materials Science and engineering Korea Advanced Institute of Science and TechnologyDaejeon 305-701Republic of Korea Department of Anesthesiology Perioperativeand Pain MedicineCenter for Accelerated Medical Innovation&Center for NanomedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA Department of Biological engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA Cardiovascular Product evaluation Center Yonsei University College of MedicineSeoul 120-752Republic of Korea Division of Cardiology Department of Internal MedicineSeverance Cardiovascular HospitalYonsei University College of MedicineSeoul 120-752Republic of Korea

Cardiovascular diseases remain the leading cause of mortality worldwide,with percutaneous coronary interventions(PCI)using drug-eluting stents(DeS)as the standard treatment for coronary artery *** advancements in DeS technology,challenges such as restenosis and stent thrombosis still necessitate further interventions and carry considerable risks,highlighting an urgent need for a novel therapeutic approach with lower restenosis rates and reduced reintervention *** balloons(DeBs)coated with anti-proliferative agents offer a novel method of local drug delivery for reducing restenosis by directly administering drugs to the lesion ***,efficient delivery of drugs within the brief procedural window while minimizing drug loss during maneuvering to the target site remains a ***,we developed a pressure-responsive and pH-triggered,paclitaxel(PTX)coated DeB catheter for rapid and high-dose delivery of paclitaxel to the lesion sites,overcoming the limitations of drug dispersion and inefficiencies associated with conventional *** the charge reversion of albumin around its isoelectric point,paclitaxel-loaded human serum albumin nanoparticles(PTX-HSA-NPs)and heparin were coated using a layer-by-layer deposition method at pH *** exposure to physiological pH(i.e.,7.4),the coating is rapidly released from the balloon *** with a protective shellac coating,the DeB achieved controlled release of high-dose paclitaxel to the arterial tissue in vivo(up to 400μg per gram tissue),exceeding current DeBs in the *** results suggest the pH-responsive,multi-layer coated DeB’s potential for superior procedural outcomes,addressing a critical unmet need in PCI.

关键词： drug-eluting balloon layer-by-layer coating coronary artery disease paclitaxel

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Highly elastic,Bioresorbable Polymeric Materials for Stretchable,Transient electronic Systems

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Nano-Micro Letters 2024年第6期16卷 1-13页

作者： jeong‑Woong Shin Dong‑Je Kim Tae‑Min Jang Won Bae Han Joong Hoon Lee Gwan‑Jin Ko Seung Min Yang Kaveti Rajaram Sungkeun Han Heeseok Kang Jun Hyeon Lim Chan‑Hwi eom Amay J.Bandodkar Hanul Min Suk‑Won Hwang KU‑KIST Graduate School of Converging Science and Technology Korea University145 Anam‑roSeongbuk‑guSeoul 02841Republic of Korea SK Hynix 2091Gyeongchung‑daeroBubal‑eupIcheon‑siGyeonggi‑do 17336Republic of Korea Hanwha Systems Co. Ltd.188Pangyoyeok‑roBundang‑guSeongnam‑siGyeonggi‑do 13524Republic of Korea Department of electrical and Computer engineering North Carolina State UniversityRaleighNC 27606USA Center for Advanced Self‑Powered Systems of Integrated Sensors and Technologies(ASSIST) North Carolina State UniversityRaleighNC 27606USA Department of Integrative energy engineering Korea University145 Anam‑roSeongbuk‑guSeoul 02841Republic of Korea Biomaterials Research Center Korea Institute of Science and Technology(KIST)5 Hwarang‑ro 14‑gilSeongbuk‑guSeoul 02792Republic of Korea Semiconductor R&D Center Samsung Electronics Co.Ltd.Hwaseong‑siGyeonggi‑do 18448Republic of Korea Center for Advanced Biomolecular Recognition Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea

Substrates or encapsulants in soft and stretchable formats are key components for transient,bioresorbable electronic systems;however,elastomeric polymers with desired mechanical and biochemical properties are very limited compared to nontransient ***,we introduce a bioresorbable elastomer,poly(glycolide-co-ε-caprolactone)(PGCL),that contains excellent material properties including high elongation-at-break(esilience and toughness,and tunable dissolution *** of PGCLs as polymer matrices,in combination with conducing polymers,yields stretchable,conductive composites for degradable interconnects,sensors,and actuators,which can reliably function under external *** of device components with wireless modules demonstrates elastic,transient electronic suture system with on-demand drug delivery for rapid recovery of postsurgical wounds in soft,time-dynamic tissues.

关键词： Biodegradable elastomer Conductive polymer composites Biomedical device Transient electronics

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An oxygenating colloidal bioink for the engineering of biomimetic tissue constructs

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Bio-Design and Manufacturing 2024年第3期7卷 240-261页

作者： Seol-Ha jeong Jarno Hiemstra Patrick V.Blokzijl Rebeca Damian-Ferrara Danilo Martins dos Santos Jéssica H.L.da Fonseca Min-Ho Kang Jihyun Kim Dilara Yilmaz-Aykut Mei L.L.Cham-Pérez Jeroen Leijten Su Ryon Shin Division of engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02139USA Leijten Lab Department of Developmental BioEngineeringFaculty of Science and TechnologyTechnical Medical CentreUniversity of TwenteDrienerlolaan 57522 NB EnschedeThe Netherlands Nanotechnology National Laboratory for Agriculture(LNNA) Embrapa InstrumentaçãoSao CarlosSao Paulo 13560-970Brazil Department of Biomedical-Chemical engineering The Catholic University of Korea43 Jibong-roBucheon-siGyeonggi-do 14662Republic of Korea Department of Biotechnology The Catholic University of Korea43 Jibong-roBucheon-siGyeonggi-do 14662Republic of Korea

ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural *** in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted *** oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain *** study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with *** report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide ***,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase *** study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release ***,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal *** showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new *** findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated *** work thereby offers a promising avenue for the development of functional tissues with e

关键词： 3D bioprinting Bioink Colloidal gels extrusion printing Oxygen-generating microparticle

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