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Open-porous magnesium-based scaffolds withstand in vitro corrosion under cyclic loading:A mechanistic study

Bioactive Materials 2023年第1期19卷 406-417页

作者： Roxane Bonithon Colin Lupton Marta Roldo joseph nicholas dunlop Gordon William Blunn Frank Witte Gianluca Tozzi Zeiss Global Centre School of Mechanical and Design EngineeringUniversity of PortsmouthAnglesea RoadPO13DJPortsmouthUnited Kingdom School of Pharmacy and Biomedical Sciences University of PortsmouthWhite Swan RoadPO12DTPortsmouthUnited Kingdom School of the Environment Geography&GeosciencesUniversity of PortsmouthBurnaby RoadPO13QLPortsmouthUnited Kingdom Department of Prosthodontics Geriatric Dentistry and Craniomandibular DisordersCharite-Universitätsmedizin BerlinAßmannshauser Straße 4-614197BerlinGermany Biotrics Bioimplants AG Ullsteinstr.10812109BerlinGermany

The successful application of magnesium(Mg)alloys as biodegradable bone substitutes for critical-sized defects may be comprised by their high degradation rate resulting in a loss of mechanical *** study investigates the degradation pattern of an open-porous fluoride-coated Mg-based scaffold immersed in circulating Hanks’Balanced Salt Solution(HBSS)with and without in situ cyclic compression(30 N/1 Hz).The changes in morphological and mechanical properties have been studied by combining in situ high-resolution X-ray computed tomography mechanics and digital volume *** in situ cyclic compression induced acceleration of the corrosion rate,probably due to local disruption of the coating layer where fatigue microcracks were formed,no critical failures in the overall scaffold were observed,indicating that the mechanical integrity of the Mg scaffolds was *** changes,due to the accumulation of corrosion debris between the scaffold fibres,resulted in a significant increase(p<0.05)in the material volume fraction from 0.52±0.07 to 0.47±0.03 after 14 days of ***,despite an increase in fibre material loss,the accumulated corrosion products appear to have led to an increase in Young’s modulus after 14 days as well as lower third principal strain(εp3)accumulation(-91000±6361μεand-60093±2414μεafter 2 and 14 days,respectively).Therefore,this innovative Mg scaffold design and composition provide a bone replacement,capable of sustaining mechanical loads in situ during the postoperative phase allowing new bone formation to be initially supported as the scaffold resorbs.

关键词： Magnesium alloys Bone regeneration In vitro corrosion X-ray computed tomography(XCT) Digital volume correlation(DVC)

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Single and multiplexed gene repression in solventogenic Clostridium via Cas12a-based CRISPR interference

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Synthetic and Systems Biotechnology 2023年第1期8卷 148-156页

作者： Rochelle Carla joseph nicholas R.Sandoval Department of Chemical and Biomolecular Engineering Tulane UniversityNew OrleansLA70118United States

The Gram-positive,spore-forming,obligate anaerobic firmicute species that make up the Clostridium genus have broad feedstock consumption capabilities and produce value-added metabolic products,but genetic manipulation is difficult,limiting their broad ***-Cas systems have recently been applied to Clostridium species,primarily using Cas9 as a counterselection marker in conjunction with plasmid-based homologous *** interference is a method that reduces gene expression of specific genes via precision targeting of a nuclease deficient Cas effector ***,we develop a dCas12a-based CRISPR interference system for transcriptional gene repression in multiple mesophilic Clostridium *** show the Francisella novicida Cas12a-based system has a broader applicability due to the low GC content in Clostridium species compared to CRISPR Cas systems derived from other *** demonstrate>99%reduction in transcript levels of targeted genes in Clostridium acetobutylicum and>75%reduction in Clostridium *** also demonstrate multiplexed repression via use of a single synthetic CRISPR array,achieving 99%reduction in targeted gene expression and elucidating a unique metabolic profile for their reduced ***,this work builds a foundation for high throughput genetic screens without genetic editing,a key limitation in current screening methods used in the Clostridium community.

关键词： CRISPR Cas12a Clostridium CRISPRi

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Artificial intelligence in gastroenterology:where are we heading?

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Frontiers of Medicine 2020年第4期14卷 511-517页

作者： joseph JY Sung nicholas CH Poon Institute of Digestive Disease Faculty of MedicineThe Chinese University of Hong KongHong KongChina Big Data Decision Analytic Cancer The Chinese University of Hong KongHong KongChina

Artificial intelligence(AI)is coming to medicine in a big *** making diagnosis in various medical conditions,following the latest advancements in scientific literature,suggesting appropriate therapies,to predicting prognosis and outcome of diseases and conditions,AI is offering unprecedented possibilities to improve care for *** is a field that AI can make a significant *** is partly because the diagnosis of gastrointestinal conditions relies a lot on image-based investigations and procedures(endoscopy and radiology).AI-assisted image analysis can make accurate assessment and provide more information than conventional *** integration of genomic,epigenetic,and metagenomic data may offer new classifications of gastrointestinal cancers and suggest optimal personalized *** managing relapsing and remitting diseases such as inflammatory bowel disease,irritable bowel syndrome,and peptic ulcer bleeding,convoluted neural network may formulate models to predict disease outcome,enhancing treatment *** and surgical robots can also assist surgeons in conducting gastrointestinal *** the advancement and new opportunities are exciting,the responsibility and liability issues of AI-assisted diagnosis and management need much deliberations.

关键词： artificial intelligence endoscopy robotics gastrointestinal diseases

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Thermal hypersensitivity in a subset of irritable bowel syndrome patients

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World Journal of Gastroenterology 2009年第26期15卷 3254-3260页

作者： QiQi Zhou Roger B Fillingim joseph L Riley Ⅲ G nicholas Verne Department of Medicine OhioState University Columbus Ohio 43210 United States College of Dentistry University of Florida Gainesville Florida 32610 United States North Florida/South Georgia Veteran Health System Gainesville Florida 32610 United States Research Service Cincinnati VAMCCincinnati Ohio 45220 United States

AIM： To characterize thermal hypersensitivity in patients with constipation- and diarrhea-predominant irritable bowel syndrome （IBS）. METHODS： Thermal pain sensitivity was tested among patients with diarrhea-predominant IBS （D-IBS） and constipation-predominant IBS （C-IBS） compared to healthy subjects. A total of 42 patients （29 female and 13 male; mean age 27.0 ＋ 6.4 years） with D-IBS; 24 patients （16 female and eight male; mean age 32.5 ：1：8.8 years） with C-IBS; and 52 control subjects （34 female and 18 male; mean age 27.3 ± 8.0 years） participated in the study. Thermal stimuli were delivered using a Medoc Thermal Sensory Analyzer with a 3 cm × 3 cm surface area. Heat pain threshold （HPTh） and heat pain tolerance （HPTo） were assessed on the left ventral forearm and left calf using an ascending method of limits. The Functional Bowel Disease Severity Index （FBDSI） was also obtained for all subjects. RESULTS： Controls were less sensitive than C-IBS and D-IBS （both at P 〈 0.001） with no differences between C-IBS and D-IBS for HPTh and HPTo. Thermal hyperalgesia was present in both groups of IBS patients relative to controls, with IBS patients reporting significantly lower pain threshold and pain tolerance at both test sites. Cluster analysis revealed the presence of subgroups of IBS patients based on thermal hyperalgesia. One cluster （17% of the sample） showed a profile of heat pain sensitivity very similar to that of healthy controls; a second cluster （47% of the sample） showed moderate heat pain sensitivity; and a third cluster （36% of the sample） showed a very high degree of thermal hyperalgesia. CONCLUSION： A subset of IBS patients had thermal hypersensitivity compared to controls, who reported significantly lower HPTh and HPTo. All IBS patients had a higher score on the FBDSI than controls. Interestingly, the subset of IBS patients with high thermal sensitivity （36%） had the highest FBDSI score compared to the other two groups of IBS patients.

关键词： Irritable bowel syndrome Visceral pain thermal hypersensitivity Heat pain threshold Heat pain tolerance

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Multimode vibrational strong coupling in direct laser written mid-IR plasmonic MIM nano-patch antennas

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Photonics Research 2023年第12期11卷 2136-2148页

作者： nicholas V.PROSCIA MICHAEL A.MEEKER nicholas SHARAC FRANK K.PERKINS CHASE T.ELLIS PAUL D.CUNNINGHAM joseph G.TISCHLER NRC Postdoc residing at U.S.Naval Research Laboratory WashingtonD.C.20375USA U.S.Naval Research Laboratory WashingtonD.C.20375USA Current address:Rigetti Computing FreemontCalifornia 94538USA Current address:Homer L.Dodge Department of Physics and Astronomy The University of OklahomaNormanOklahoma 73019USA

Strong coupling of mid-infrared(mid-IR)vibrational transitions to optical cavities provides a means to modify and control a material’s chemical reactivity and offers a foundation for novel chemical detection ***,the relatively large volumes of the mid-IR photonic cavities and weak oscillator strengths of vibrational transitions restrict vibrational strong coupling(VSC)studies and devices to large ensembles of molecules,thus representing a potential limitation of this nascent ***,we experimentally and theoretically investigate the mid-IR optical properties of 3D-printed multimode metal-insulator-metal(MIM)plasmonic nanoscale cavities for enabling strong light-matter interactions at a deep subwavelength *** observe strong vibration-plasmon coupling between the two dipolar modes of the L-shaped cavity and the carbonyl stretch vibrational transition of the polymer *** cavity mode volume is half the size of a typical square-shaped MIM geometry,thus enabling a reduction in the number of vibrational oscillators to achieve strong *** resulting three polariton modes are well described by a fully coupled multimode oscillator model where all coupling potentials are *** 3D printing technique of the cavities is a highly accessible and versatile means of printing arbitrarily shaped submicron-sized mid-IR plasmonic cavities capable of producing strong light–matter interactions for a variety of photonic or photochemical ***,similar MIM structures fabricated with nanoscopic voids within the insulator region could constitute a promising microfluidic plasmonic cavity device platform for applications in chemical sensing or photochemistry.

关键词： coupling vibrational shaped

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Estimation of spatial and temporal water requirements of grain amaranth using satellite,local and virtual weather stations datasets in Uganda

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International Journal of Agricultural and Biological Engineering 2016年第2期9卷 85-97页

作者： joseph Kyagulanyi Isa Kabenge Noble Banadda John Muyonga Peter Mulamba nicholas Kiggundu Department of Agricultural and Biosystems Engineering Makerere UniversityP.O.Box 7062KampalaUganda Department of Food Technology and Nutrition Makerere University P.O Box 7062 KampalaUganda

In this study,an integrated approach incorporating Remote Sensing(RS),Geographical Information System(GIS),local meteorological weather stations’data and NASA’s virtual meteorological stations’data were used to quantify Grain Amaranth(GA)water requirements in ***-Monieth method within CropWAT8 model and Surface Energy Balance Algorithm for Land(SEBAL)Model was used to quantify the *** Difference Vegetation Index(NDVI),daily spatial distribution of Evapotranspiration(ET),Land Surface Temperature(LST)and surface albedo were extracted from satellite *** ratio of effective rainfall(Pe)to Potential Evapotranspiration(PET)–(Pe/PET)and time series for NDVI were computed to determine the growth stage of GA in different *** GA water demand was the highest in Karamoja sub-region(467.5 mm/season)and the lowest in Tororo(174.1 mm/season).The growing season for GA in most areas of Uganda was from March to *** of evapotranspiration in Karamoja sub-region with SEBAL model corresponded to the NDVI extracted,especially for highly vegetated *** indicated that if GA was planted during the late September and early October in Karamoja sub-region,despite the decreasing moisture levels,the crop could have sufficient water supply during emergence to *** ability to utilize low available moisture levels makes GA a potential crop to bridge the gap(due to the elongated drought)for the food production cycle in Karamoja sub-region.

关键词： grain amaranth water requirement remote sensing SEBAL evapotranspiration Uganda

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The formation of massif anorthosite:Petrology in reverse

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Geoscience Frontiers 2013年第2期4卷 195-198页

作者： nicholas Arndt ISTerre Universite Joseph Fourier:UMR5275CNRS1381 rue de la Piscine38400 St Martin d'HeresFrance

Massif anorthosites form when basaltic magma differentiates in crustal magma chambers to form lowdensity plagioclase and a residual liquid whose density was greater than that of enclosing crustal rocks. The plagioclase and minor pyroxene crystallized in-situ on the floor of the magma chamber to produce the anorthosite complex,and the residual liquid migrated downwards,eventually to solidify as dense Fe-rich cumulates some of which were removed to the *** movements were facilitated by high temperatures in Proterozoic continental crust,thus explaining the restriction of large anorthosite massifs to this period in Earth history.

关键词： Anorthosite Petrology Proterozoic

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Intrusions of the Panxi region,China,and their magmatic ore deposits

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Geoscience Frontiers 2013年第5期4卷 479-480页

作者： nicholas Arndt ISTerre Universite Joseph Fourier38400 St Martin d'HeresFrance

The intrusions of the Panzhihua-Xichang（Panxi） region in southwest China have become well known in the past decade because they host large and rich magmatic oxide deposits that are mined for Fe,Ti and *** intrusions form part of the Emeishan large igneous province（ELIP）,which is commonly believed to be the product of melting in a mantle *** ELIP was emplaced about 260 Ma ago,at the same time as the end-Guadalupian mass *** investigation of the Panxi intrusions therefore provides information relevant to three broad areas of the earth sciences：（1）the petrogenesis of mafic magmas,

关键词： Intrusions magmatic nicholas

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Macrophage migration inhibitory factor inhibits BMP-4 induced apoptosis

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Advances in Bioscience and Biotechnology 2012年第8期3卷 1206-1213页

作者： nicholas Matluk Tamara Adams Aldona Karaczyn joseph Verdi Maine Medical Center Research Institute Research Drive Scarborough USA

Non-canonical bone morphogenic protein (BMP) pathway signaling plays a critical role during embryonic neurogenesis, inducing apoptosis and eliminating an excess of neural progenitor cells, in preparation for the population of the neural stem cell niches. Our previous work discovered that non-canonical BMP signaling also induced the expression of the anti-apoptotic cytokine macrophage migration inhibitory factor (MIF). Because there are residual neural progenitors that escape BMP induced apoptosis, we believed the expression of MIF could be used to counter this specific type of developmental apoptosis. In vitro studies using P19 cells and ex vivo studies using E13 neural progenitor from wild type and mif-/-mice revealed that overexpression of mif was able to counteract BMP induced apoptosis, while in contrast ablation of mif resulted in a dramatic increase in apoptosis. Despite this finding, it is interesting to note that mif-/-mice, while presenting an overall increase in apoptosis are viable, ablation of mif expression in zebrafish and frog are embryonic lethal, suggesting a redundant or non-critical role of MIF in the developing mammalian embryo.

关键词： MIF BMP Apoptosis Embryonic Neural Stem Cell

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Bronchodilator responsiveness assessed by forced oscillometry and multiple breath washout techniques in preschool children

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Pediatric Investigation 2018年第2期2卷 83-89页

作者： nicholas L.Friedman joseph M.McDonough Xuemei Zhang Erik B.Hysinger Kelly M.Adams Julian L.Allen Division of Pulmonary Medicine The Children's Hospital of PhiladelphiaPhiladelphia PA USA Department of Pediatrics Madigan Army Medical Center Tacoma WAUSA Division of Pulmonary Medicine The Children's Hospital of PhiladelphiaPhiladelphia PA USA Division of Pulmonary Medicine Cincinnati Children's Hospital Medical Center Cincinnati OH USA Division of Pulmonary Medicine Northwell Health System Lake SuccessNY USA

Importance:The forced oscillation (FOT) and multiple breath washout (MBW) techniques are passive tests of lung function,and are reliable for preschool-age *** has not been comparison testing to determine which test could more accurately differentiate between healthy controls and poorly controlled asthmatics,or differentiate a response to bronchodilator ***:To determine whether the MBW and/or FOT could differentiate between healthy controls and poorly controlled asthmatics,and whether the two tests could detect a response to bronchodilator ***:Twenty-eight healthy controls and 23 poorly controlled asthmatics 3-6 years of age *** subjects were administered the MBW followed by the FOT.A bronchodilator was then administered and testing was *** Rank Sum tests were used to compare the difference between healthy controls and poorly controlled *** Signed Rank tests were used to compare the pre-and post-bronchodilator ***:Neither MBW nor FOT differentiated healthy controls from poorly controlled asthmatics (pre-bronchodilator data);both groups had similar baseline gas mixing and airway *** was no improvement in any MBW outcomes post-bronchodilator *** detected a significant and similar degree of improvement in the airway mechanics in both ***:Neither MBW nor FOT differentiated between poorly controlled asthmatics (when well) and healthy *** did not detect a significant bronchodilator response in either subject group,whereas FOT detected a similar degree of bronchodilator responsiveness in both *** discrepancy may reflect differential changes in airway mechanics and gas mixing properties in response to bronchodilators.

关键词： Forced oscillation technique Multiple breath washout Pediatric lung function measurement Pediatric asthma

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