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Simple and customizable method for fabrication of high-aspect ratio microneedle molds using low-cost 3D printing

microsystems & Nanoengineering 2019年第1期5卷 250-263页

作者： Kevin J.Krieger Nicky Bertollo manita Dangol John T.Sheridan madeleine m.lowery Eoin D.O’Cearbhaill UCD Centre for Biomedical Engineering University College DublinBelfieldDublin 4Ireland School of mechanical&materials Engineering University College DublinBelfieldDublin 4Ireland School of Electrical&Electronic Engineering University College DublinBelfieldDublin 4Ireland

We present a simple and customizable microneedle mold fabrication technique using a low-cost desktop SLA 3D *** opposed to conventional microneedle fabrication methods,this technique neither requires complex and expensive manufacturing facilities nor expertise in *** most low-cost 3D-printed microneedles to date display low aspect ratios and poor tip sharpness,we show that by introducing a two-step“Print&Fill”mold fabrication method,it is possible to obtain high-aspect ratio sharp needles that are capable of penetrating *** first the effect of varying design input parameters and print settings,it is shown that printed needles are always shorter than *** decreasing input height,needles also begin displaying an increasingly greater than specified needle base *** factors contribute to low aspect ratio needles when attempting to print submillimeter height *** setting input height tall enough,it is possible to print needles with high-aspect ratios and tip radii of 20–40μ*** tip sharpness is smaller than the specified printer ***,high-aspect ratio sharp needle arrays are printed in basins which are backfilled and cured in a second step,leaving sub-millimeter microneedles exposed resulting microneedle arrays which can be used as male *** female master molds are then formed from the fabricated microneedle *** the molds,both carboxymethyl cellulose loaded with rhodamine B as well as polylactic acid microneedle arrays are produced and their quality examined.A skin insertion study is performed to demonstrate the functional capabilities of arrays made from the fabricated *** method can be easily adopted by the microneedle research community for in-house master mold fabrication and parametric optimization of microneedle arrays.

关键词： needle cost printer

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High human disturbance decreases individual variability in skink escape behavior

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Current Zoology 2020年第1期66卷 63-70页

作者： Dana m.WILLIAmS Phat-Tan NGUYEN Kemal CHAN madeleine KROHN Daniel T.BLUmSTEIN Department of Ecology&Evolutionary Biology University of California621 Young Drive SouthLos AngelesCA90095-1606USA

Animals living around people may modify their antipredator behavior as a function of proximity to humans,and this response has profound implications for whether or not a population can coexist with *** asked whether inland blue-tailed skinks Emoia impar modified their individual antipredator behavior as a function of differential exposure to *** conducted multiple consecutive flushes and recorded 2 measures of antipredator response:flight initiation distance(FID),the distance from a threatening stimulus at which an individual flees,and distance fled,the distance an individual fled after a *** used a multiple model comparison approach to quantify variation in individual escape behavior across multiple approaches and to test for differences in between-individual variation among *** found that individuals tolerated closer approach and fled shorter distances at locations with relatively less human disturbance than at locations with medium and high human disturbance,*** addition,skinks living at high human disturbance sites had less variable FIDs than at low human disturbance *** theories may explain these *** against less favorable phenotypes has reduced behavioral variation in urban habitats and behavioral plasticity allows individuals to flexibly adjust their behavioral patterns in response to human *** results highlight the importance of studying variation within populations,at the individual level,which may better elucidate the impact that human disturbance has on the behavioral composition of populations.

关键词： distance fled Emoia impar flight initiation distance habitat sorting habituation urbanization

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Co-delivery of PARP and PI3K inhibitors by nanoscale metal-organic frameworks for enhanced tumor chemoradiation

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Nano Research 2019年第12期12卷 3003-3017页

作者： megan J.Neufeld Allison N.DuRoss madeleine R.Landry Hayden Winter Andrea m.Goforth Conroy Sun Department of Pharmaceutical Sciences College of PharmacyOregon State UniversityPortlandOregon 97201USA Department of Chemistry Portland State University1719 SW 10th AvePortlandOregon 97201USA Department of Radiation medicine Oregon Health&Science University3181 S.W.Sam Jackson Park RdPortlandOregon 97239USA

Due to their complementary activity,the use of DNA damage repair(DDR)inhibitors during radiotherapy(RT)has yielded promising ***,this approach is often hindered by toxicity and poor in vivo stability of the DDR in *** scale metal-organic frameworks(nmOFs)represent an emerging class of crystalline materials which exhibit advantageous properties over traditional nanomaterials and demonstrate great potential in ***,a unique,synergistic treatment strategy for enhancing the therapeutic efficacy of RT vianmOF-mediated drug delivery and RT enhancement was evaluated.A nmOF containing the high-Zelement Hf and the ligand 1,4-dicarboxybenzene(Hf-BDC)was synthesized and loaded with the two DDR inhibitor drugs,talazoparib and buparlisib(TB@Hf-BDC-PEG).TB@Hf-BDC-PEGaugmented RT by increasing reactive oxygen species generation and thus DNA damage of which repair was inhibited *** enhancement was demonstrated in vivo where the combination of concurrent radiation with in travenous TB@Hf-BDC-PEG administration resulted in improved tumor control and increased ***,no apparent toxicity was observed with nmOF treatment,supporting its potential as an attractive candidate over traditional nano *** work provides the first report of nmOFs employed to enhance thetherapeutic response to RT through DDR inhibitor delivery and physical radiation dose enhancement.

关键词： nano scale metal-organic frameworks chemoradiotherapy DNA damage repair inhibitors drug delivery radiation dose enhancement

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Catquest-9SF functioning over a decade–a study from the Swedish National Cataract Register

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Eye and Vision 2020年第1期7卷 553-562页

作者： mats Lundström maria Kugelberg Per montan Ingela Nilsson madeleine Zetterberg Konrad Pesudovs Anders Behndig Department of Clinical Sciences/Ophthalmology Faculty of MedicineLund UniversityTrossögatan 437137 KarlskronaLundSweden Department of Clinical Neuroscience Division of Ophthalmology and VisionKarolinska InstitutetStockholmSweden St Erik Eye Hospital StockholmSweden Capio medocular LundSweden Department of Clinical Neuroscience Institute of Neuroscience and PhysiologySahlgrenska Academy at the University of GothenburgGothenburgSweden University of New South Wales AdelaideSAAustralia Department of Clinical Sciences/Ophthalmology UmeåUniversityUmeåSweden

Background:The Swedish National Cataract Register(NCR)collects data on cataract surgery outcomes during march,including patient-reported outcomes using the Catquest-9SF questionnaire for over 11 *** studies from NCR have shown that the preoperative visual acuity has improved over *** main purpose of this study was to evaluate the Catquest-9SF Rasch scoring performance in this changing environment.A second purpose was to describe clinical data over the same period for those who completed the ***:The performance of the Catquest-9SF was analysed by a separate Rasch analysis for each year,resulting in a preoperative and postoperative score for each participating patient in the annual *** clinical data and questionnaire scoring were analysed for each year in the period 2008-2018 ***:Data were available for 42,023 eyes for 11 annual cohorts(2008-2018).The psychometric properties of the questionnaire were stable during the study *** separation(precision)for the whole period was 2.58 and varied between 2.45 and *** person reliability was 0.87 and varied between 0.86 and *** targeting of question difficulty to person ability became less accurate over time meaning that the item activities became easier to carry out without *** average targeting for the whole period was−2.06 and changed from−1.92 in 2008 to−2.31 in *** person score improved both before surgery and after surgery,indicating that patients are undergoing surgery at a more able level and getting better *** average improvement by surgery decreased from 3.41 logits in 2008 to 3.21 logits in 2018(p=0.003).Over time,patient age decreased from 75 to 74 years(pmen decreased from 63.9 to 57.9%(pmean preoperative visual acuity in both the operated eye and the better eye improved over time(0.47 to 0.40 logmAR,pmAR,pmean post

关键词： Cataract extraction Outcomes Questionnaire Patient-reported outcomes Rasch analysis

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Enrichment of retinal ganglion and müller glia progenitors from retinal organoids derived from human induced pluripotent stem cells-possibilities and current limitations

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World Journal of Stem Cells 2020年第10期12卷 1171-1183页

作者： Kristine Karla Freude Sarkis Saruhanian Alanna mcCauley Colton Paterson madeleine Odette Annika Oostenink Poul Hyttel mark Gillies Henriette Haukedal miriam Kolko Department of Veterinary and Animal Sciences Group of Stem Cell Models for Studies of Neurodegenerative DiseasesSection for Pathobiological SciencesFaculty of Health and Medical SciencesUniversity of CopenhagenFrederiksberg 1870Denmark Department of Drug Design and Pharmacology University of CopenhagenCopenhagen 2100Denmark Save Sight Institute South BlockSydney Eye HospitalSydney 2000Australia Department of Ophthalmology Copenhagen University HospitalRigshospitalet-GlostrupGlostrup 2600Denmark

BACKGROUND Retinal organoids serve as excellent human-specific disease models for conditions affecting otherwise inaccessible retinal tissue from *** permit the isolation of key cell types affected in various eye diseases including retinal ganglion cells(RGCs)and müller *** To refine human-induced pluripotent stem cells(hiPSCs)differentiated into threedimensional(3D)retinal organoids to generate sufficient numbers of RGCs and müller glia progenitors for downstream *** In this study we described,evaluated,and refined methods with which to generate müller glia and RGC progenitors,isolated them via magnetic-activated cell sorting,and assessed their lineage stability after prolonged 2D *** progenitor populations were characterized via quantitative PCR and immunocytochemistry,and the ultrastructural composition of retinal organoid cells was *** Our study confirms the feasibility of generating marker-characterized müller glia and RGC progenitors within retinal *** retinal organoids can be dissociated and the müller glia and RGC progenitor-like cells isolated via magnetic-activated cell sorting and propagated as *** Enrichment of müller glia and RGC progenitors from retinal organoids is a feasible method with which to study cell type-specific disease phenotypes and to potentially generate specific retinal populations for cell replacement therapies.

关键词： Human induced pluripotent stem cells Retinal organoids Retinal ganglion cells müller glia Progenitors Cell-type enrichment

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Hearing Loss among Grain millers in the Informal Sector in Benin

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Occupational Diseases and Environmental medicine 2022年第1期10卷 35-47页

作者： mênonli Adjobimey Antoine Vikkey Hinson Rose mikponhoué Eyidi m. madeleine Concheta Tchibozo Esdras Hountohotegbe Paul Ayélo Research and Education Unit in Occupational Health and Environment FSS Cotonou Benin Occupational Health Service of the National University Hospital of Pneumo-Phtisiology of Cotonou Cotonou Benin Laboratory of Epidemiology of Chronic and Neurological Diseases FSS Cotonou Benin

Introduction: Noise-induced hearing loss is a preventable health problem worldwide. However, it continues to affect workers especially in the informal sector, due to the lack of medical and environmental monitoring. In Benin, millers are highly exposed. The objective of the study was to assess the hearing health situation of grain millers in the Dantokpa market in 2020. methods: This was a cross-sectional study that included by exhaustive recruitment 57 millers. The data were collected using a standardized questionnaire followed by blood pressure measurements, noise levels and the performance of audiometries. Descriptive and univariate analysis was performed. Results: The sample consisted only of men. The median age was 25 years with extremes of 18 and 50 years. Noise levels at the workstation ≥ 85 dB (A) were obtained for 94.74% of the workers. No worker was wearing hearing protection equipment. The prevalence of hearing loss was 87.72% (95% CI = [76.32%;94.92%]) and that of occupational deafness was 29.82% (95% CI = [18.43% - 43.40%]) which was associated with age over 28 and high blood pressure. An awareness campaign with donation of hearing pads was carried out. Conclusion: Hearing loss is important among millers who do not benefit from any supervision because they are in the informal sector. A restructuring of this sector is necessary for the hearing health of workers.

关键词： Noise Hearing Loss Blood Pressure millers Benin

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Thermomechanical Characterisation of Compressed Clay Bricks Reinforced by Thatch Fibres for the Optimal Use in Building

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materials Sciences and Applications 2018年第12期9卷 913-935页

作者： madeleine Nitcheu Pierre meukam Jean Claude Damfeu Donatien Njomo Department of Physics Faculty of Science Environmental Energy Technologies Laboratory (EETL) University of Yaounde I Yaounde Cameroon Department of Basic Scientific Teaching School of Geology and Mining Engineering University of Ngaoundere Ngaoundere Cameroon Laboratory of Energy Water and Environment (L3E) National Advanced School of Engineering Yaounde Cameroon

Thatch fibres grow in large quantity in the Adamawa region of Cameroon. During the long dry season, these fibres cause numerous fire incidents, which not only devastate large areas of cash crops, but also contribute to increase emissions of greenhouse gases into the atmosphere. This article aims to show how fibres could be used with compressed clay bricks to manufacture an insulating material used in building. Four fibre contents 1%, 2%, 3% and 4% made up the sample studied. The asymmetric hot plate methodology was used to determine the thermophysical properties of these composite materials. The volumetric heat capacity and the thermal effusivity of these materials were estimated. These two parametres were used to determine their apparent thermal conductivities. The results obtained show that the thermal conductivity decreases as the volume of fibres in the mixture increases. It is 0.689 W·m-1·K-1 for simple compressed clay bricks and 0.510 W·m-1·K-1 for a dosage at 3% of thatch fibres. In a bit to validate the results of the pilot study of the apparent thermal conductivity, the heat mass capacity of this composite material was achieved through the use of the dehydration method. The relative difference obtained with the results of the volumetric heat capacity carried out with these two methods was good. All results showed that the use of fibres in compressed laterite brick gives a more insulating composite material that respects Civil Engineering Norms.

关键词： Thatch Fibres Clay Bricks Thermo mechanical Properties Transient method mixing method

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Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AmPK activation in high fat fed Zucker fatty rats

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World Journal of Gastroenterology 2017年第21期23卷 3805-3814页

作者： Yi Tan Jane Kim Jing Cheng madeleine Ong Wei-Guo Lao Xing-Liang Jin Yi-Guang Lin Linda Xiao Xue-Qiong Zhu Xian-Qin Qu School of medical and molecular Biosciences University of Technology Sydney The Second Affiliated Hospital of Wenzhou medical University

AIm To investigate protective effects and molecular mechanisms of green tea polyphenols(GTP) on nonalcoholic fatty liver disease(NAFLD) in Zucker fatty(ZF) *** male ZF rats were fed a high-fat diet(HFD) for 2 wk then treated with GTP(200 mg/kg) or saline(5 m L/kg) for 8 wk, with Zucker lean rat as their control. At the end of experiment, serum and liver tissue were collected for measurement of metabolic parameters, alanine aminotransferase(ALT) and aspartate aminotransferase(AST), inflammatory cytokines and hepatic triglyceride and liver histology. Immunoblotting was used to detect phosphorylation of AmP-activated protein kinase(AmPK) acetyl-Co A carboxylase(ACC), and sterol regulatory element-binding protein 1c(SREBP1c). RESULTS Genetically obese ZF rats on a HFD presented with metabolic features of hepatic pathological changes comparable to human with NAFLD. GTP intervention decreased weight gain(10.1%, P = 0.052) and significantly lowered visceral fat(31.0%, P mpared with ZF-controls, GTP treatment significantly reduced fasting serum insulin, glucose and lipids levels. Reduction in serum ALT and AST levels(both P ment also attenuated the elevated TNFα and IL-6 in the circulation. The increased hepatic TG accumulation and cytoplasmic lipid droplet were attenuated by GTP treatment, associated with significantly increased expression of AmPK-Thr172(P minished hepatic lipogenesis and triglycerides out flux from liver in GTP treated rats. CONCLUSION The protective effects of GTP against HFD-induced NAFLD in genetically obese ZF rats are positively correlated to reduction in hepatic lipogenesis through upregulating the AmPK pathway.

关键词： Non-alcoholic fatty liver disease Green tea polyphenols Hepatic lipogenesis Inflammatory cytokines AmP-activated protein kinase

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monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia

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Genes & Diseases 2024年第1期11卷 413-429页

作者： Dongsheng Zhang Wenjuan Tang Haitao Niu William Tse Hai-Bin Ruan Helmut Dolznig Thomas Knosel Friedrich Karl-Heinz madeleine Themanns Jiang Wang mingquan Song Lee Denson Lukas Kenner Richard moriggl Yi Zheng Xiaonan Han Division of Hematology and Oncology Division of Cancer BiologyDepartment of MedicineMetroHealth Medical Center(MHMC)Case Western Reserve University(CWRU)School of MedicineClevelandOH 44109USA Cancer Genomics and Epigenomics Program Case Comprehensive Cancer CenterCase Western Reserve University(CWRU)ClevelandOH 44106USA Division of Gastroenterology Hepatology and NutritionCincinnati Children’s Hospital Medical Center(CCHMC)CincinnatiOH 45229USA Children’s Hospital of Fudan University Shanghai 201102China School of medicine Jinan UniversityGuangzhouGuangdong 510632China Laboratory Animal Science(ILAS) Chinese Academy of Medical Science(CAMS)and Peking Union Medical College(PUMC)Beijing 100006China Department of Integrative Biology and Physiology University of Minnesota Medical SchoolMinneapolisMI 55455USA Institute of medical Genetics Medical University of ViennaVienna 1040Austria Institute of Pathology Ludwig-Maximilians-University MunichMunich 80539Germany Institute of Biochemistry II University Hospital JenaJena 07743Germany Laboratory Animal Pathology University of Veterinary Medicine ViennaVienna 1210Austria Department of Pathology University of CincinnatiCincinnatiOH 45221USA Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266005China Department of Pathology Medical University of ViennaVienna 1040Austria Ludwig Boltzmann Institute for Cancer Research Vienna 1090Austria medical University of Vienna Vienna 1040Austria Institute of Animal Breeding and Genetics University of Veterinary Medicine ViennaVienna 1210Austria Division of Experimental Hematology CCHMCCincinnatiOH 45229USA

CDC42 controls intestinal epithelial(IEC)stem cell(IESC)*** aberrant CDC42 initiates intestinal inflammation or neoplasia is *** utilized models of inflam-matory bowel diseases(IBD),colorectal cancer,aging,and IESC injury to determine the loss of intestinal Cdc42 upon inflammation and *** specimens were collected to determine the levels of CDC42 in IBD or colorectal ***42 floxed mice were crossed with Villin-Cre,Villin-CreERT2 and/or Lgr5-eGFP-IRES-CreERT2,or Bmi1-CreERT2 mice to generate Cdc42 deficient ***,colitis,aging,and intestinal organoid were used to evaluate CDC42 upon mucosal inflammation,IESC/progenitor regenerative capacity,and IEC *** studies revealed that increased CDC42 in colorectal cancer correlated with lower survival;in contrast,lower levels of CDC42 were found in the inflamed IBD *** Cdc42 depletion significantly reduced Lgr5+IEsCs,increased progenitors'hyperplasia,and induced mucosal inflammation,which led to crypt *** Cdc42 depletion markedly enhanced irra-diation-or chemical-induced *** or inhibition of Cdc42 reduced colonic Lgr5+IESC *** conclusion,depletion of Cdc42 reduces the IESC regeneration and IEC repair,leading to prolonged mucosal *** monogenic loss of Cdc42 in-duces mucosal inflammation,which could result in intestinal neoplasia in the context of aging.

关键词： Cell divisioncycle 42(CDC42) Colitis Colorectal cancer(CRC) Inflammatory bowel diseases(IBD) Intestinal epithelial cell(IEC) Intestinal epithelial stem cell(IESC) Irradiation

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A Survey of the Floristic Diversity of the National Park of marahouéafter the Armed Conflicts in Ivory Coast

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Open Journal of Forestry 2016年第4期6卷 259-268页

作者： Yao Sadaiou Sabas Barima Kouassi Apollinaire Kouakou Akoua Tamia madeleine Kouakou Yao Charles Sangne Training and Research Unit in Environment University Jean Lorougnon Guédé Daloa Ivory Coast

most of the Ivorian areas designated as protected were trickled in for various agricultural activities. For these last few decades, the situation worsened in Ivory Coast because these protected areas were not guarded during the armed conflict of the years 2002-2011. The objective of this study is to assess the condition in which the floristic diversity of the National park of marahoué (NPm) is after the armed conflicts of the years 2000. To achieve our purpose, a sampling has been conducted along five transects that go through different environments: inner the park, the edge of the park and the non-domanial property. A 20 × 20 m plot square has been settled in each of these environments along each transect and each one separated from one another by 200 m. Four (4) other pilots plots of 20 × 20 m have been built up inside the park, relatively in the protected areas. Regarding these surveys, 303 plant species have been identified among which the most important are Fabaceae (6.27%), Euphorbiaceae (5.28%) and Rubiaceae (5.28%) families. Twenty-four (24) species have a particular status according to the International Union for the Nature Conservation among which nineteen (19), and about 79.16% have been seen in the relatively protected areas. One of these species, Baphia Bancoensis Aubrév, is endemic in Ivory Coast. In the park, the agricultural activities have reduced the number of trees which diameter is over 30 cm. Although the infiltration of clandestines in the NPm started long before the beginning of the conflicts, our work nevertheless permitted to point out them. During this period, these infiltrations were accelerated mainly because these people were looking for new lands to cultivate cocoas trees.

关键词： Floristic Diversity Conflicts Anthropogenic Activities Endemism Ivory Coast

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