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High-resolution two-photon polymerization:the most versatile technique for the fabrication of microneedle arrays

Microsystems & Nanoengineering 2021年第5期7卷 1-17页

作者： Zahra Faraji Rad philip D.Prewett Graham J.Davies School of Mechanical and Elearical Engineering University of Southern QueenslandSpringfield CentralQLD 4300Australia Department of Mechanical Engineering University of BirminghamBirmingham B152TTUK Oxacus Ltd Dorchester-on-Thames 0X107HNUK Faculty of Engineering UNSW AustraliaKensingtonNSW 2052Australia College of Engineering and Physical Sciences School of EngineeringUniversity of BirminghamBirmingham B152TTUK

Microneedle patches have received much interest in the last two decades as drug/vaccine delivery or fluid sampling systems for diagnostic and monitoring *** are manufactured using a variety of additive and subtractive micromanufacturing *** the last decade,much attention has been paid to using additive manufacturing techniques in both research and industry,such as 3D printing,fused deposition modeling,inkjet printing,and two-photon polymerization(2PP),with 2PP being the most flexible method for the fabrication of microneedle arrays.2PP is one of the most versatile and precise additive manufacturing processes,which enables the fabrication of arbitrary three-dimensional(3D)prototypes directly from computer-aided-design(CAD)models with a resolution down to 100 *** to its unprecedented flexibility and high spatial resolution,the use of this technology has been widespread for the fabrication of bio-microdevices and bio-nanodevices such as microneedles and microfluidic *** is a pioneering transformative technology that facilitates the fabrication of complex miniaturized structures that cannot be fabricated with established multistep manufacturing methods such as injection molding,photolithography,and ***,microstructures are designed according to structural and fluid dynamics considerations rather than the manufacturing constraints imposed by methods such as machining or etching *** article presents the fundamentals of 2PP and the recent development of microneedle array fabrication through 2PP as a precise and unique method for the manufacture of microstructures,which may overcome the shortcomings of conventional manufacturing processes.

关键词： resolution needle additive

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Inhibition of vascular adhesion protein-1 modifies hepatic steatosis in vitro and in vivo

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World Journal of Hepatology 2020年第11期12卷 931-948页

作者： Emma L Shepherd Sumera Karim philip N Newsome Patricia F Lalor Centre for Liver and Gastroenterology Research Birmingham National Institute for Health ResearchBirmingham Biomedical Research CentreInstitute of Immunology and ImmunotherapyUniversity of BirminghamBirmingham B152TTWest MidlandsUnited Kingdom Liver Unit Queen Elizabeth HospitalUniversity Hospitals BirminghamBirmingham B152TTWest MidlandsUnited Kingdom

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is associated with obesity,insulin resistance and dyslipidaemia and currently is estimated to affect up to a third of all individuals in developed *** standard of care for patients varies according to disease stage,but includes lifestyle interventions common insulin sensitizers,antioxidants and lipid ***,to date specific therapies have shown little histological or fibrosis stage improvement in large clinical trials,and there is still no licensed therapy for *** the high prevalence,limited treatment options and significant screening costs for the general population,new treatments are urgently *** To assess the potential for inhibition of the amine oxidase enzyme vascular adhesion protein-1(VAP-1)to modify hepatic lipid accumulation in *** We have used immunochemical and qPCR analysis to document expression of VAP-1 and key functional proteins and transporters across the NAFLD *** then utilised hepatocytes in culture and human precision cut liver slices in concert with selective enzyme activity inhibitors to test the effects of activating the semicarbazide-sensitive amine oxidase activity of VAP-1 on hepatic lipid uptake and triglyceride export.A murine model of NAFLD was also used to determine the consequences of VAP-1 knockout and gene expression arrays were used to quantify the effects of VAP-1 activity on key lipid modifying and proinflammatory gene *** We confirmed that increasing severity of NAFLD and progression to cirrhosis was associated with a significant increase in hepatocellular VAP-1 *** in vitro exposed to recombinant VAP-1 and its substrate methylamine showed increased lipid accumulation as determined by quantification of Oil Red O *** was recapitulated using hydrogen peroxide,and lipid accumulation was accompanied by changes in expression of the lipid transporter molecules FABP3,FATP6,insulin recep

关键词： Non-alcoholic fatty liver disease Hepatocyte Lipid Cell biology Vascular adhesion protein-1 Steatosis

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Correlation and prognostic significance of beta-galactoside alpha-2,6-sialyltransferase and serum monosialylated alpha-fetoprotein in hepatocellular carcinoma

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World Journal of Gastroenterology 2005年第42期11卷 6701-6706页

作者： Terence CW Poon Clarissa HS Chiu Paul BS Lai Tony SK Mok Benny Zee Anthony TC Chan Joseph JY Sung philip J Johnson Department of Medicine and Therapeutics Sir YK Pao Cancer Centre the Chinese University of Hong Kong Prince of Wales Hospital NT Hong Kong China Department of Clinical Oncology Sir YK Pao Cancer Centre the Chinese University of Hong Kong Prince of Wales Hospital NT Hong Kong China Department of Surgery Sir YK Pao Cancer Centre the Chinese University of Hong Kong Prince of Wales Hospital NT Hong Kong China Cancer Research UK Institute for Cancer Studies University of Birmingham Vincent Drive Edgbaston Birmingham B15 2TT United Kingdom

AIM： To investigate the correlation between tissue ST6Gal I and serum msAFP in HCC patients, and to investigate their prognostic significance. METHODS： Preoperative sera, paired tumorous and non-tumorous tissues were collected from 19 consecutive patients who had undergone surgical resection of HCC. ST6Gal I activities in the tissues were measured by an in vitro microsomal enzyme activity assay. The percentages of tumor-specific msAFP in the sera were also estimated by an isoelectric focusing-immunoblotting assay. RESULTS： The tumor ST6Gal I activity was negatively correlated with serum msAFP percentage （r = -0.53, P = 0.019）. Both decreased tumor ST6Gal I activity and increased serum msAFP percentage were associated with poor tumor cell differentiation. Univariate analyses showed that both decreased tumor ST6Gal I activity （P = 0.028）, increased serum msAFP percentage （P = 0.034） and poor tumor cell differentiation （P = 0.031）were associated with shorter overall survival. Multivariate analysis using the Cox regression model showed that the preoperative serum msAFP percentage （P = 0.022） and tumor cell differentiation status （P = 0.048） were independent prognostic indicators for patient overall survival. CONCLUSION： Our results indicate that the presence of msAFP in blood circulation is associated with a decreased activity of ST6Gal I activity in HCC. Both tissue ST6Gal I and serum msAFP are potential prognostic markers for patients with operable HCC.

关键词： Alpha-fetoprotein Beta-galactoside alpha-2,6-sialyltransferase Hepatocellular carcinoma Patientsurvival Cell differentiation

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Simulated annealing algorithm for ill-posed or ill-conditioning deconvolution problem

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Chinese Journal of Acoustics 1996年第2期15卷 141-151页

作者： WANG Yingmin MA Yuanliang LIU Jianmin and philip R. Atkins (Institute of Acoustic Engineering, Northwestern Polytechnical University Xi’an 710072) (School of Electronic & Electrical Engineering The University of Birnimgham, Birmingham B15 2tt, U.K.)

A simulated annealing deconvolution technique dealing with the ill-posed and ill-Conditioning problems is presented. Following a survey about direct and iterative deconvolution techniques, the simulated annealing approach for ill-posed and ill-conditioning decon volution is introduced. With comparison to some deconvolution techniques the new approach is described in details. A specific ill-posed and ill-Conditioning deconvolution example is consid ered and the deconvolution results using the simulated annealing approach and some conventional techniques such as clipped inverse filtering, reblurring, multiple-operator, constrained iteration, etc., are given. It has shown that the simulated annealing approach fights against the ill-posed and ill-conditioning successfully.

关键词： Annealing algorithm Deconvolution

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Association of IL-17A and IL-17F Gene Polymorphisms with Acute Immune Thrombocytopenia in Egyptian Children

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Open Journal of Blood Diseases 2018年第3期8卷 49-60页

作者： Shereen philip Aziz Heba A. Ahmed Ramadan A. Mahmoud Marwa Ahmed Mahmoud Department of Clinical Pathology Faculty of Medicine Sohag University Sohag Egypt Department of Pediatrics Faculty of Medicine Sohag University Sohag Egypt Department of Physiology Faculty of Medicine Sohag University Sohag Egypt

Background: IL-17 is an inflammatory cytokine that plays a crucial role in many autoimmune diseases. Aim: To investigate the association of IL-17A rs2275913 and IL-17F rs763780 gene polymorphisms with acute immune thrombocytopenic purpura (ITP) in Egyptian children. Patients and methods: We examined 80 patients (male/female, 33/47;median age, 7 years old) diagnosed with acute ITP and 55 healthy controls (male/female, 28/27;median age, 7 years old). Genotyping was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: In the acute ITP group compared to control, statistical analysis of the genotype frequencies (GG, AG, AA) of the IL-17A rs2275913 polymorphism and its alleles (A, G) showed no significant difference between the two groups (p > 0.05). Interestingly, the IL17A rs2275913 GG genotype was associated with early recovery (p = 0.04). As regard the genotype frequencies of the IL-17F rs763780 polymorphism, there was statistical significant difference in the tt and TC genotype frequencies between the case and control groups (p = 0.001 and p = 0.003, respectively). The number of IL-17F rs763780 T alleles was significantly higher in acute ITP patients as compared with children in the control group (p Conclusion: The present findings indicate that the IL-17 polymorphism IL-17F rs763780, but not IL-17A rs2275913 may be associated with a higher risk of acute ITP in Egyptian children.

关键词： Acute Immune Thrombocytopenia IL-17F IL-17A Polymorphism Genotyping

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Generation of knockout rabbits using transcription activator-like effector nucleases

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Cell Regeneration 2014年第1期3卷 21-29页

作者： Yu Wang Nana Fan Jun Song Juan Zhong Xiaogang Guo Weihua Tian Quanjun Zhang Fenggong Cui Li Li philip N Newsome Jon Frampton Miguel A Esteban Liangxue Lai Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine South China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthGuangzhou 510530China NIHR Liver BRU and Centre for Liver Research University of BirminghamBirminghamUK Liver and Hepatobiliary Unit Queen Elizabeth Hospital BirminghamBirminghamUK Institute for Biomedical Research College of Medical and Dental SciencesUniversity of BirminghamBirmingham B152TTUK

Zinc-finger nucleases and transcription activator-like effector nucleases are novel gene-editing platformscontributing to redefine the boundaries of modern biological research. They are composed of a non-specificcleavage domain and a tailor made DNA-binding module, which enables a broad range of genetic modifications byinducing efficient DNA double-strand breaks at desired loci. Among other remarkable uses, these nucleases havebeen employed to produce gene knockouts in mid-size and large animals, such as rabbits and pigs, *** approach is cost effective, relatively quick, and can produce invaluable models for human disease studies,biotechnology or agricultural purposes. Here we describe a protocol for the efficient generation of knockout rabbitsusing transcription activator-like effector nucleases, and a perspective of the field.

关键词： Rabbits Animal models Zinc-finger nucleases Transcription activator-like effector nucleases TALENs Genome editing Knockout

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Nanotechnology:fundamental research to product development

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Engineering Sciences 2012年第5期10卷 42-44页

作者： Graham J Davie Zahra F Rad Carl Anthony philip Prewett Jing Peng Robert Nordon The University of New South Wales Sydney NSW 2025 Australi The University of Birmingham Birmingham B15 2TT UK Harbin Institute of Technology Harbin 150001 China

The concept of an integrated "lab on a chip" has long been a goal for the micro-electro-mechanical-systems(MEMS) *** would entail the integration of not only the sampling and analysis of various functions,but also the ability to transmit this information off the chip to a central *** paper describes the initial steps in the fabrication of a "lab on a chip" which would continually analyze blood sampled via microneedles using techniques such as nano plasmonics,specifically,concentrations of *** analysis could then be transmitted off the chip using digital signal *** paper describes the analysis and optimization of the microneedle shape and size and the fabrication of the resulting needles in silicon using deep reactive ion etching(DRIE).The paper also describes the opportunities for fabrication of such needles in alternative materials and describes the issues that still have to be overcome before such an integrated device is realized.

关键词： MEMS micro-needles lab on a chip nanotechnology

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High-fidelity replication of thermoplastic microneedles with open microfluidic channels

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Microsystems & Nanoengineering 2017年第1期3卷 96-106页

作者： Zahra Faraji Rad Robert E.Nordon Carl J.Anthony Lynne Bilston philip D.Prewett Ji-Youn Arns Christoph H.Arns Liangchi Zhang Graham J.Davies Graduate School of Biomedical Engineering University of New South WalesSydneyNSW 2052Australia School of Mechanical Engineering University of BirminghamBirmingham B152TTUK School of Mechanical and Manufacturing Engineering University of New South WalesSydneyNSW 2052Australia Prince of Wales Clinical School University of New South WalesSydneyNSW 2052Australia School of Petroleum Engineering University of New South WalesSydneyNSW 2052Australia

Development of microneedles for unskilled and painless collection of blood or drug delivery addresses the quality of healthcare through early intervention at *** with submicron to millimeter features have been fabricated from materials such as metals,silicon,and polymers by subtractive machining or ***,to date,large-scale manufacture of hollow microneedles has been limited by the cost and complexity of microfabrication *** paper reports a novel manufacturing method that may overcome the complexity of hollow microneedle *** microneedles with open microfluidic channels are fabricated by laser *** replicas are manufactured from these templates by soft-embossing with high fidelity at submicron *** manufacturing advantages are(a)direct printing from computeraided design(CAD)drawing without the constraints imposed by subtractive machining or etching processes,(b)high-fidelity replication of prototype geometries with multiple reuses of elastomeric molds,(c)shorter manufacturing time compared to three-dimensional stereolithography,and(d)integration of microneedles with open-channel *** work will address development of open-channel microfluidics for drug delivery,fluid sampling and analysis.

关键词： drug delivery laser lithography microneedles point-of-care diagnostics soft embossing

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CEPC Technical Design Report

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Radiation Detection Technology and Methods 2024年第1期8卷 I0003-I0016,1-1091页

作者： Waleed Abdallah Tiago Carlos Adorno de Freitas Konstantin Afanaciev Shakeel Ahmad Ijaz Ahmed Xiaocong Ai Abid Aleem Wolfgang Altmannshofer Fabio Alves Weiming An Rui An Daniele Paolo Anderle Stefan Antusch Yasuo Arai Andrej Arbuzov Abdesslam Arhrib Mustafa Ashry Sha Bai Yu Bai Yang Bai Vipul Bairathi Csaba Balazs philip Bambade Yong Ban Tripamo Bandyopadhyay Shou-Shan Bao Desmond P.Barber Ayse Bat Varvara Batozskaya Subash Chandra Behera Alexander Belyaev Michele Bertucci Xiao-Jun Bi Yuanjie Bi Tianjian Bian Fabrizio Bianchi Thomas Biekotter Michela Biglietti Shalva Bilanishvili Deng Binglin Denis Bodrov Anton Bogomyagkov Serge Bondarenko Stewart Boogert Maarten Boonekamp Marcello Borri Angelo Bosotti Vincent Boudry Mohammed Boukidi Igor Boyko Ivanka Bozovic Giuseppe Bozzi Jean-Claude Brient Anastasiia Budzinskaya Masroor Bukhari Vladimir Bytev Giacomo Cacciapaglia Hua Cai Wenyong Cai Wujun Cai Yijian Cai Yizhou Cai Yuchen Cai Haiying Cai Huacheng Cai Lorenzo Calibbi Junsong Cang Guofu Cao Jianshe Cao Antoine Chance Xuejun Chang Yue Chang Zhe Chang Xinyuan Chang Wei Chao Auttakit Chatrabhuti Yimin Che Yuzhi Che Bin Chen Danping Chen Fuqing Chen Fusan Chen Gang Chen Guoming Chen Hua-Xing Chen Huirun Chen Jinhui Chen Ji-Yuan Chen Kai Chen Mali Chen Mingjun Chen Mingshui Chen Ning Chen Shanhong Chen Shanzhen Chen Shao-Long Chen Shaomin Chen Shiqiang Chen Tianlu Chen Wei Chen Xiang Chen Xiaoyu Chen Xin Chen Xun Chen Xurong Chen Ye Chen Ying Chen Yukai Chen Zelin Chen Zilin Chen Gang Chen Boping Chen Chunhui Chen Hok Chuen Cheng Huajie Cheng Shan Cheng Tongguang Cheng Yunlong Chi Pietro Chimenti Wen Han Chiu Guk Cho Ming-Chung Chu Xiaotong Chu Ziliang Chu Guglielmo Coloretti Andreas Crivellin Hanhua Cui Xiaohao Cui Zhaoyuan Cui Brunella D'Anzi Ling-Yun Dai Xinchen Dai Xuwen Dai Antonio De Maria Nicola De Filippis Christophe De La Taille Francesca De Mori Chiara De Sio Elisa Del Core Shuangxue Deng Wei-Tian Deng Zhi Deng Ziyan Deng Bhupal Dev Tang Dewen Biagio Di Micco Ran Ding Siqin Dingl Yadong Ding Haiyi Dong Jianin AGH University of Science and Technology Faculty of Physics and Applied Computer ScienceKrakow Anhui University HefeiAnhui Applied Physics Department Federal Urdu University of ArtsScience and TechnologyIslamabad Banaras Hindu University Institute of ScienceVaranasi Bandirma Onyedi Eylul University Bandirma Beihang University Beijing Beijing Computational Science Research Center Beijing Beijing Conveyi LTD Beijing Beijing Glass Research Institute Co. LtdBeijing Beijing Institute of Technology Beijing Beijing Normal University Beijing Brown University ProvidenceRI Budker Institute of Nuclear Physics Novosibirsk Cadi Ayyad University Laboratory of Fundamental and Applied PhysicsPolydisciplinary FacultyMarrakech Cairo University Giza Center for Theory and Computation National Tsing Hua UniversityHsinchu Central China Normal University WuhanHubei Central South University ChangshaHunan Centro de Fisica Teorica de Particulas Universidade Tecnica de LisboaLisboa Chengdu KaitengSifang Digital Radio&TV Equipment Co. LtdChengduSichuan China academy of engineering physics MianyangSichuan China building materials academy Beijing China Center of Advanced Science and Technology Beijing China Institute of Atomic Energy Beijing China Jiliang University HangzhouZhejiang China Nuclear Instrument CO. LTDBeijing China University of Geosciences Beijing China University of Geosciences WuhanHubei China University of Mining and Technology XuzhouJiangsu China West Normal University NanchongSichuan Chongqing University Department of PhysicsChongqing Chulalongkorn University Bangkok City University of Hong Kong Department of PhysicsHong Kong Cockcroft Institute Daresbury Cornell University IthacaNY CPPM(AMU/IPhU&CNRS/INP) Marseille Dalian Minzu University DalianLiaoning Dalian University of Technology Department of PhysicsDalian Deutsches Elektronen-Synchrotron DESY Hamburg Dzhelepov Laboratory of Nuclear Problems of Joint Institute for Nuclear Research(DLNP JINR) Dubna East China University Of Science And Technol

The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international *** complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs *** its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs *** the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of *** Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering ***,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection *** is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 *** commencement of experiments and data collection could potentially be initiated in the mid-2030s.

关键词： initiated exceeding precise

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