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Fabrication of 3D-printed molds for polydimethylsiloxane-based microfluidic devices using a liquid crystal display-based vat photopolymerization process:printing quality,drug response and 3D invasion cell culture assays

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microsystems & Nanoengineering 2023年第6期9卷 205-219页

作者： matthew D.Poskus Tuo Wang Yuxuan Deng Sydney Borcherding jake Atkinson Ioannis K.Zervantonakis Department of Bioengineering UPMC Hillman Cancer CenterUniversity of PittsburghPittsburghPAUSA mcGowan Institute of Regenerative medicine PittsburghPAUSA

microfluidic platforms enable more precise control of biological stimuli and environment dimensionality than conventional macroscale cell-based assays;however,long fabrication times and high-cost specialized equipment limit the widespread adoption of microfluidic technologies.Recent improvements in vat photopolymerization three-dimensional(3D)printing technologies such as liquid crystal display(LCD)printing offer rapid prototyping and a cost-effective solution to microfluidic fabrication.Limited information is available about how 3D printing parameters and resin cytocompatibility impact the performance of 3D-printed molds for the fabrication of polydimethylsiloxane(PDmS)-based microfluidic platforms for cellular studies.Using a low-cost,commercially available LCD-based 3D printer,we assessed the cytocompatibility of several resins,optimized fabrication parameters,and characterized the minimum feature size.We evaluated the response to both cytotoxic chemotherapy and targeted kinase therapies in microfluidic devices fabricated using our 3D-printed molds and demonstrated the establishment of flow-based concentration gradients.Furthermore,we monitored real-time cancer cell and fibroblast migration in a 3D matrix environment that was dependent on environmental signals.These results demonstrate how vat photopolymerization LCD-based fabrication can accelerate the prototyping of microfluidic platforms with increased accessibility and resolution for PDmS-based cell culture assays.

关键词： invasion printing culture

Highwall mining of thick,steeply dipping coal–A case study in geotechnical design and recovery optimization

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International Journal of mining Science and Technology 2019年第5期29卷 777-780页

作者： Chris Ross David Conover jake Baine Agapito Associate Inc.GoldenCOUSA Westmoreland Kemmerer LLC Kemmerer MineKemmererUSA

Highwall mining of thick(up to 30.48 m)steeply dipping(20°or more)coal seams provides many chal lenges,both geotechnically and operationally,as seam dips near or in excess of highwall mining machine capabilities are encountered.maximizing coal recovery while maintaining highwall stability requires innovative techniques with regard to web and barrier pillar layout,depth of penetration,and choice of mining horizon within the seam.Stability of highwall mining slopes,openings,and pillarsare typically analyzed using the ARmPS-HWm program,as well as LAmODEL,UDEC and SLOPE/W modeling.Highwall stability can be maintained,and highwall mining production optimized by applying design cri-teria in creative ways,including alternating miner penetration depths and initiating mining of thick seams toward the bottom of the seam.Highwall mining of thick,steeply dipping coal requires careful planning and execution,including close cooperation between geotechnical design engineers,the mining company,and the highwall mining contractor.This paper describes the application of creative design techniques to a specific pit arrangement at the Westmoreland Kemmerer mine,Kemmerer,Wyoming.Highwall mining was accomplished by UGm ADDCAR Systems,LLC on a contract basis.

关键词： mining thick optimization

Dynamic energy system modeling using hybrid physics-based and machinelearning encoder–decoder models

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能源与人工智能(英文)

能源与人工智能(英文) 2022年第3期9卷 128-138页

作者： Derek machalek jake Tuttle Klas Andersson Kody m.Powell Department of Chemical Engineering University of UtahSalt Lake CityUTUnited States of America Taber International LLCUnited States of America Department of Space Earthand EnvironmentUniversity of ChalmersGothenburgSweden Department of mechanical Engineering University of UtahSalt Lake CityUTUnited States of America

Three model configurations are presented for multi-step time series predictions of the heat absorbed by thewater and steam in a thermal power plant. The models predict over horizons of 2, 4, and 6 steps into thefuture, where each step is a 5-minute increment. The evaluated models are a pure machine learning model, anovel hybrid machine learning and physics-based model, and the hybrid model with an incomplete dataset. Thehybrid model deconstructs the machine learning into individual boiler heat absorption units: economizer, waterwall, superheater, and reheater. Each configuration uses a gated recurrent unit (GRU) or a GRU-based encoder–decoder as the deep learning architecture. mean squared error is used to evaluate the models compared totarget values. The encoder–decoder architecture is over 11% more accurate than the GRU only models. Thehybrid model with the incomplete dataset highlights the importance of the manipulated variables to the system.The hybrid model, compared to the pure machine learning model, is over 10% more accurate on averageover 20 iterations of each model. Automatic differentiation is applied to the hybrid model to perform a localsensitivity analysis to identify the most impactful of the 72 manipulated variables on the heat absorbed in theboiler. The models and sensitivity analyses are used in a discussion about optimizing the thermal power plant.

关键词： Hybrid model Encoder-decoder Time series Automatic differentiation Thermal power plant

On the Hybrid model of Nerve Pulse: mathematical Analysis and Numerical Results

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Journal of Applied mathematics and Physics 2023年第8期11卷 2373-2396页

作者： Alexander mengnjo jake Leonard Nkeck Department of mathematics Faculty of Science University of Buea Buea Cameroon

Amongst the important phenomena in neurophysiology, nerve pulse generation and propagation is fundamental. Scientists have studied this phenomena using mathematical models based on experimental observations on the physiological processes in the nerve cell. Widely used models include: the Hodgkin-Huxley (H-H) model, which is based entirely on the electrical activity of the nerve cell;and the Heimburg and Jackson (H-J), model based on the thermodynamic activity of the nerve cell. These classes of models do not, individually, give a complete picture of the processes that lead to nerve pulse generation and propagation. Recently, a hybrid model proposed by mengnjo, Dikandé and Ngwa (m-D-N), takes into consideration both the electrical and thermodynamic activities of the nerve cell. In their work, the first three bound states of the model are analytically computed and they showed great resemblance to some of the experimentally observed pulse profiles. With these bound states, the m-D-N model reduces to an initial value problem of a linear parabolic partial differential equation with variable coefficients. In this work we consider the resulting initial value problem and, using the theory of function spaces, propose and prove conditions under which such equations will admit unique solutions. We then verify that the resulting initial value problem from the m-D-N model satisfies these conditions and so has a unique solution. Given that the derived initial value problem is complex and there are no known analytic techniques that can be deployed to obtain its solution, we designed a numerical experiment to estimate the solutions. The simulations revealed that the unique solution is a stable pulse that propagates in the x-t plane with constant velocity and maintains the shape of the initial profile.

关键词： Nerve Impulse Nerve Pulse Propagation Hodgkin-Huxley Equation Korteweg-de Vries Equation Heimburg Jackson model Neurophysiology

multimodal alarm behavior in urban and rural gray squirrels studied by means of observation and a mechanical robot

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Current Zoology 2010年第3期56卷 313-326页

作者： Sarah R.PARTAN Andrew G FULmER maya A.m.GOUNARD jake E.REDmOND Hampshire College School of Cognitive Science

Urbanization of animal habitats has the potential to affect the natural communication systems of any species able tosurvive in the changed environment. Urban animals such as squirrels use multiple signal channels to communicate, but it is unknownhow urbanization has affected these behaviors. multimodal communication, involving more than one sensory modality,can be studied by use of biomimetic mechanical animal models that are designed to simulate the multimodal signals and be presentedto animal subjects in the field. In this way the responses to the various signal components can be compared and contrastedto determine whether the multimodal signal is made up of redundant or nonredundant components. In this study, we presentedwild gray squirrels in relatively urban and relatively rural habitats in Western massachusetts with a biomimetic squirrel modelthat produced tail flags and alarm barks in a variety of combinations. We found that the squirrels responded to each unimodalcomponent on its own, the bark and tail flag, but they responded most to the complete multimodal signal, containing both theacoustic and the moving visual components, providing evidence that in this context the signal components are redundant and thattheir combination elicits multimodal enhancement. We expanded on the results of Partan et al. (2009) by providing data on signalingbehavior in the presence and absence of conspecifics, suggesting that alarm signaling is more likely if conspecifics arepresent. We found that the squirrels were more active in the urban habitats and that they responded more to tail flagging in theurban habitats as compared to the rural ones, suggesting the interesting possibility of a multimodal shift from reliance on audio tovisual signals in noisier more crowded urban habitats [Current Zoology 56 (3): 313-326, 2010].

关键词：观测手段多式联运机器人行为报警机械灰色农村

Facile synthesis of insulin fusion derivatives through sortase A ligation

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2719-2725页

作者： maria m.Disotuar jake A.Smith Jinze Li Steve Alam Nai-Pin Lin Danny Hung-Chieh Chou Department of Biochemistry School of MedicineUniversity of UtahSalt Lake CityUT 84112USA Division of Endocrinology and Diabetes Department of PediatricsSchool of MedicineStanford UniversityPalo AltoCA 94305USA

Insulin derivatives such as insulin detemir and insulin degludec are U.S.Food and Drug Administration(FDA)-approved long-acting insulin currently used by millions of people with diabetes.These derivatives are modified in C-terminal B29 lysine to retain insulin bioactivity.New and efficient methods for facile synthesis of insulin derivatives may lead to new discovery of therapeutic insulin.Herein,we report a new method using sortase A(SrtA)-mediated ligation for the synthesis of insulin derivatives with high efficiency and functional group tolerance in the C-terminal B chain.This new insulin molecule(Ins-SA) with an SrtA-recognizing motif can be conjugated to diverse groups with N-terminal oligoglycines to generate new insulin derivatives.We further demonstrated that a new insulin derivative synthesized by this SrtA-mediated ligation shows strong cellular and in vivo bioactivity.This enzymatic method can therefore be used for future insulin design and development.

关键词： Diabetes mellitus Insulin synthesis Sortase A(SrtA)ligation Albumin-binding peptide SA21 Long-acting insulin

Diabetic heart disease:A clinical update

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World Journal of Diabetes 2021年第4期12卷 383-406页

作者： jake Rajbhandari Cornelius James Fernandez mayuri Agarwal Beverly Xin Yi Yeap Joseph m Pappachan College of medical and Dental Sciences University of Birmingham Medical SchoolBirmingham B152THUnited Kingdom Department of Endocrinology and metabolism Pilgrim HospitalBoston PE219QSUnited Kingdom Department of medicine The University of Manchester Medical SchoolManchester M139PLUnited Kingdom Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

Diabetes mellitus(Dm) significantly increases the risk of heart disease,and Dmrelated healthcare expenditure is predominantly for the management of cardiovascular complications.Diabetic heart disease is a conglomeration of coronary artery disease(CAD),cardiac autonomic neuropathy(CAN),and diabetic cardiomyopathy(DCm).The Framingham study clearly showed a 2 to 4-fold excess risk of CAD in patients with Dm.Pathogenic mechanisms,clinical presentation,and management options for Dm-associated CAD are somewhat different from CAD among nondiabetics.Higher prevalence at a lower age and more aggressive disease in Dm-associated CAD make diabetic individuals more vulnerable to premature death.Although common among diabetic individuals,CAN and DCm are often under-recognised and undiagnosed cardiac complications.Structural and functional alterations in the myocardial innervation related to uncontrolled diabetes result in damage to cardiac autonomic nerves,causing CAN.Similarly,damage to the cardiomyocytes from complex pathophysiological processes of uncontrolled Dm results in DCm,a form of cardiomyopathy diagnosed in the absence of other causes for structural heart disease.Though optimal management of Dm from early stages of the disease can reduce the risk of diabetic heart disease,it is often impractical in the real world due to many reasons.Therefore,it is imperative for every clinician involved in diabetes care to have a good understanding of the pathophysiology,clinical picture,diagnostic methods,and management of diabetes-related cardiac illness,to reduce morbidity and mortality among patients.This clinical review is to empower the global scientific fraternity with up-to-date knowledge on diabetic heart disease.

关键词： Diabetic heart disease Type 2 diabetes mellitus Type 1 diabetes mellitus Coronary artery disease Cardiovascular disease Cardiac autonomic neuropathy Diabetic cardiomyopathy

An economic analysis of varicella immunization in the Singapore military

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Journal of medical Colleges of PLA(China) 2016年第1期31卷 43-50页

作者： jake J.K.Goh marc Ho W.m.Koh Vernon J.Lee Specialist medicine Centre AFPN 0047 27 Medical Drive #08-01 Singapore 117510 Singapore National University of Singapore MD3 16 Medical Drive Singapore 117597 Singapore

Background:Varicella outbreaks occur frequently in closed environments such as those of militaries.This paper compares the economic outcomes of varicella vaccination in enlisted servicemen without prior reported varicella infection or vaccination.methods:We analyzed the economic outcomes of a varicella vaccination program on all enlisted servicemen without prior reported varicella infection or vaccination in the Singapore Armed Forces(SAF) between December 11,2010–December 20,2013,compared with the previous program of varicella vaccination only for selected personnel between December 1,2007–December 10,2010.Results:In the at-risk population of all active SAF servicemen,the program of varicella vaccination for all servicemen without prior reported varicella infection or vaccination upon enlistment would save 72.0 work days per 1000(95% CI:61.2-82.9),valued at SG$6,544 per 1000(95% CI:6,524-6,564),i.e.,costing SG$91.5 per work day saved(95% CI:78.7-107.3).This also results in a reduction of 2.7 varicella cases per 1000 and 5.43 outbreaks per 10000,or a total savings of SG$1,695 per 1000(95% CI:–2,730-6,834),taking into account the cost of work days lost over a three-year period,compared with the previous regime of vaccinations only for selected individuals.Conclusion:The varicella vaccination strategy targeting all enlisted servicemen without prior reported varicella infection or vaccination is able to prevent varicella infections and outbreaks,thus reducing absenteeism and days lost.

关键词： Varicella Vaccination military Singapore Economic analysis

The influence of large dams building on resettlement in the Upper mekong River

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Journal of Geographical Sciences 2013年第5期23卷 947-957页

作者： ZHANG Yong HE Daming LU Ying FENG Yan jake REZNICK Yunnan Key Laboratory of International Rivers and Transboundary Eco-security Yunnan University Kunming 650091 China Asian International Rivers Center Yunnan University Kunming 650091 China Heifer International China Office Chengdu 610045 China

This paper seeks to quantify the social and economic impact of resettlement based on the physiographic element changes post relocation. We focus on communities affected by the Nuozhadu hydropower project, the largest existing hydropower project on the mainstream of the Upper mekong River. Soil and meteorological data were collected from the Soil Spatial Database and the China Terrestrial Ecological Information Spatial meteorology Database, while social and economic data were collected via field surveys. We have three major con- clusions：（1） Communities will be relocated to a new climate and new elevation, moving from a north tropical climate zone under 700 m to a subtropical climate zone above 700 m. （2） Physiographic element changes due to relocation will reduce household economic income. After relocation, the annual family income of the Shidaimao group decreased by 62%; the annual family income of the other 5 study groups （Lasa, Hani, Nochangchangyi, mengsa, and Dawazi） dropped by 65%. （3） Communities relocated across the study township are 61.1% less connected with their former relatives after relocation while family-to-family free labor exchange, a previous community norm, decreased by 91%. China＇s dam resettlement compensation system focuses on the loss of economic resources after relocation. However, this study finds that the physiographic elements of the relocation sites are an important driver of ensuring economic growth and stability after relocation. As a result, we recommend more attention be paid to physiographic continuity when designing relocation models.

关键词： Upper mekong River resettlement influence physiographic element displaced community large dam building Lancang River