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Novel,non-colonizing,single-strain live biotherapeutic product ADS024 protects against Clostridioides difficile infection challenge in vivo

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World Journal of Gastrointestinal Pathophysiology 2023年第4期14卷 71-85页

作者： christopher k murphy Michelle M O’Donnell James W Hegarty Sarah Schulz Colin Hill R Paul Ross Mary C Rea Ronald Farquhar Laurent Chesnel Research and Development Adiso Therapeutics Inc.ConcordMA 01742United States APC Microbiome Ireland University College CorkCork T12 K8AFIreland Teagasc Food Research Centre Moorepark FermoyCork P61 C996Ireland Executive Leadership Team Adiso Therapeutics Inc.ConcordMA 01742United States

BACkGROUND The Centers for Disease Control and Prevention estimate that Clostridioides difficile(***)causes half a million infections(CDI)annually and is a major cause of total infectious disease death in the United States,causing inflammation of the colon and potentially deadly *** recently reported the isolation of ADS024,a Bacillus velezensis(***)strain,which demonstrated direct in vitro bactericidal activity against ***,with minimal collateral impact on other members of the gut *** this study,we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse *** To investigate the in vivo efficacy of *** ADS024 in protecting against CDI challenge in mouse *** To mimic disruption of the gut microbiota,the mice were exposed to vancomycin prior to dosing with *** the mouse single-dose study,the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h,8 h,and 24 h after a single oral dose of 5×108 colony-forming units(CFU)/mouse of freshly grown *** single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024,and a group that was not pre-dosed with vancomycin and received a single dose of *** ADS024 colonies[assessed by quantitative polymerase chain reaction(qPCR)using ADS024-specific primers]were counted on agar *** the 28-d miniature swine study,qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5×109 CFU for 28 consecutive days,followed by MiSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on *** studies were performed to determine the efficacy of ADS024 in a mouse model of CDI:Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical mani

关键词： Gut Single-strain live biotherapeutic product ADS024 Clostridioides difficile Clostridioides difficile challenge model Microbiota

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Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： christopher J.O’Connell Matthew J.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA James L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

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Uterine receptivity and the plasma membrane transformation

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Cell Research 2004年第4期14卷 259-267页

作者： christopher R murphy Department of Anatomy and Histology The University of Sydney NSW 2006. Australia

This review begins with a brief commentary on the diversity of placentation mechanisms, and then goes on to examine the extensive alterations which occur in the plasma membrane of uterine epithelial cells during early pregnancy across species. Ultrastructural, biochemical and more general morphological data reveal that strikingly common phenomena occur in this plasma membrane during early pregnancy despite the diversity of placental types-from epitheliochorial to hemochorial, which ultimately form in different species. To encapsulate the concept that common morphological and molecular alterations occur across species, that they are found basolaterally as well as apically, and that moreover they are an ongoing process during much of early pregnancy, not just an event at the time attachment, the term ’plasma membrane transformation’ is suggested which also emphasises that alterations in this plasma membrane during early pregnancy are key to uterine receptivity.

关键词： uterine epeithelial cells membrane tranformation.

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Novel theoretical constraints for color-octet scalar models

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Chinese Physics C 2019年第9期43卷 1-11页

作者： Li Cheng Otto Eberhardt christopher W.murphy Institute of Applied Physics and Computational Mathematics Beijing 100094China Instituto de Fisica Corpuscular Universitat de Valencia-CSICApt.Correus 22085E-46071 ValenciaSpain Department of Physics Brookhaven National LaboratoryUptonNew York11973USA

We study the theoretical constraints on a model whose scalar sector contains one color octet and one or two color singlet SU(2)L *** ensure unitarity of the theory,we constrain the parameters of the scalar potential for the first time at the next-to-leading order in perturbation ***,we derive new conditions guaranteeing the stability of the *** employ the HEPfit package to extract viable parameter regions at the electroweak scale and test the stability of the renormalization group evolution up to the multi-TeV ***,we set upper limits on the scalar mass *** results are given for both cases with and without a second scalar color singlet.

关键词： beyond the Standard Model extension of Higgs sector EW symmetry breaking

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Numerical prediction of the frictional losses in sliding bearings during start-stop operation

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Friction 2021年第3期9卷 583-597页

作者： Florian kÖNIG christopher SOUS Georg JACOBS Institute for Machine Elements and Systems Engineering Rheinisch-Westfälische Technische Hochschule Aachen UniversitySchinkelstraße 10Aachen 52062Germany

With the increased use of automotive engine start-stop systems,the numerical prediction and reduction of frictional losses in sliding bearings during starting and stopping procedures has become an important *** engineering practice,numerical simulations of sliding bearings in automotive engines are performed with statistical asperity contact models with empirical values for the necessary surface *** aim of this study is to elucidate the applicability of these approaches for the prediction of friction in sliding bearings subjected to start-stop *** this purpose,the friction performance of sliding bearings was investigated in experiments on a test rig and in transient mixed elasto-hydrodynamic simulations in a multi-body simulation environment(mixed-EHL/MBS).In mixed-EHL/MBS,the extended Reynold’s equation with flow factors according to Patir and Cheng has been combined on the one hand with the statistical asperity contact model according to Greenwood and Tripp and on the other hand with the deterministic asperity contact model according to *** detailed comparison of simulation and experimental results clarifies that the application of statistical asperity contact models with empirical values of the necessary inputs leads to large deviations between experiment and *** actual distribution and position of surface roughness,as used in deterministic contact modelling,is necessary for a reliable prediction of the frictional losses in sliding bearings during start-stop operation.

关键词： sliding bearing friction wearing-in contact model,mixed elasto-hydrodynamic simulation

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Pediatric inflammatory bowel disease

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World Journal of Gastroenterology 2006年第20期12卷 3204-3212页

作者： karen A Diefenbach christopher k Breuer Department of Surgery Yale University School of Medicine Division of Pediatric Surgery330 Cedar StreetRm. 132 FMBNorth HavenCT 06520United States

Inflammatory bowel disease is an important cause of gastrointestinal pathology in children and adolescents. The incidence of pediatric inflammatory bowel disease is increasing; therefore, it is important for the clinician to be aware of the presentation of this disease in the pediatric population. Laboratory tests, radiology studies, and endoscopic procedures are helpful in diagnosing inflammatory bowel disease and differentiating between Crohn＇s disease and ulcerative colitis. Once diagnosed, the goal of medical management is to induce remission of disease while minimizing the side effects of the medication. Specific attention needs to be paid to achieving normal growth in this susceptible population. Surgical management is usually indicated for failure of medical management, complication, or malignancy. Algorithms for diagnostic evaluation and treatment of pediatric inflammatory bowel disease are presented. The specific psychosocial issues facing these patients are also discussed in this review as are the future goals of research in the complex problem of pediatric inflammatory bowel disease.

关键词： Pediatric Inflammatory bowel Ulcerative colitis Crohn's disease

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MicroRNA-based therapeutics for optic neuropathy:opportunities and challenges

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Neural Regeneration Research 2021年第10期16卷 1996-1997页

作者： Heather k.Mak christopher k.S.Leung Department of Ophthalmology and Visual Sciences The Chinese University of Hong KongHong Kong Special Administrative RegionChina

Optic nerve degeneration is a major cause of irreversible blindness worldwide with glaucoma being the most common optic neuropathy,affecting approximately 76 million people worldwide in *** optic nerve comprises axons of retinal ganglion cells(RGCs),the output neurons of the inner *** RGCs and axons from degeneration and regenerating RGC axons to preserve and recover vision in patients with progressive optic neuropathy is an unmet *** embryonic neurons,mature neurons of the mammalian central nervous system fail to regenerate their axons following *** age-related loss of axon regenerative capacity of RGCs over time renders vision loss from optic neuropathy *** failure of injured RGCs to regenerate axons is largely attributed to inhibitory molecules in the extrinsic environment and a change in the intrinsic molecular makeup of aging *** studies have demonstrated that RGCs require specific molecular signals for the stimulation of axon growth even without inhibitory molecules in the extrinsic environment,leading successive efforts to focus on uncovering the intrinsic signaling pathways that control axon extension during RGC development.

关键词： neuropathy degeneration stimulation

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Potential Use of Strain Hardening ECC in Permanent Formwork with Small Scale Flexural Beams

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Journal of Wuhan University of Technology(Materials Science) 2009年第3期24卷 482-487页

作者：李贺东 christopher k Y Leung Department of Civil Engineering Hong Kong University of Science and Technology

Utilizing pre-cast ECC panels as participating permanent formwork of concrete members, and the validity of using ECC to disperse the single crack in concrete into multiple ones in ECC were studied. In the process, totally two kinds of ECC with different tensile properties, 7 series of flat panels with different top surface figures and 3 U-shape panels with different inner surface forms were investigated. To evaluate the performance of the permanent formworks, small ECC-concrete composite beams were cast and tested mechanically. The 4-point bending test results show that the use of pre-cast ECC panels as permanent formwork can significantly improve the load capacity and toughness of a concrete member, effectively dispersing single widely opened crack in concrete into multiple ones in ECC. Most permanent formworks show perfect bond with the concrete cast on them, while the ones with partially debonded zone achieve the best mechanical performance. The U-shape permanent formworks show better performances than the flat ones, achieving much betler improvements in both the load capacity and toughness, together with better crack width control.

关键词： pseudo strain hardening cementitious composites permanent formwork toughness crack

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High-cycle Fatigue Life Extension of Glass Fiber/Polymer Composites with Carbon Nanotubes

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Journal of Wuhan University of Technology(Materials Science) 2009年第2期24卷 167-173页

作者： christopher S Grimmer C k H Dharan Berkeley Composites Laboratory University of California 5135 Etcheverry Hall Berkeley CA94720-1740 USA

The present work shows that the addition of small volume fractions of multi-walled carbon nanotubes （CNTs） to the matrix results in a significant increase in the high-cycle fatigue life. It is proposed that carbon nanotubes tend to inhibit the formation of large cracks by nucleating nano-scale damage zones. In addition, the contribution to energy absorption from the fracture of nanotubes bridging across nano-scale cracks and from nanotube pull-out from the matrix are mechanisms that can improve the fatigue life. An energy-based model was proposed to estimate the additional strain energy absorbed in fatigue. The distributed nanotubes in the matrix appear to both distribute damage as well as inhibit damage propagation resulting in an overall improvement in the fatigue strength of glass fiber composites.

关键词： glass fiber composites carbon nanotubes fatigue strain energy

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Characterisation of dissolved organic matter in stormwater using high-performance size exclusion chromatography

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Journal of Environmental Sciences 2016年第4期28卷 236-245页

作者： Huiping Huang christopher W.k.Chow Bo Jin School of Chemical Engineering The University of Adelaide School of Earth and Environmental Sciences The University of Adelaide Australian Water Quality Centre SA Water Corporation

Understanding the complexity of dissolved organic matter（DOM）in stormwater has drawn a lot of interest,since DOM from stormwater causes not only environmental impacts,but also worsens downstream aquatic quality associated with water supply and *** study introduced and employed high-performance size exclusion chromatography（HPSEC）coupled with an ultraviolet–visible（UV–vis）diode array detector to assess changes in stormwater-associated DOM *** DOM was also analysed in relation to storm event characteristics,water quality and spectroscopic *** tools were used to determine the correlations within DOM and water quality *** showed that dissolved organic carbon（DOC）and UV absorbance at 254 nm（UV（254））as conventional DOM parameters were found to be correlated well to the changes in stormwater quality during each of the three storm events *** detector wavelengths（210and 254 nm）and their ratio（A（210）/A（254））were found to provide additional information on the physiochemical properties of stormwater-associated *** study indicated that A（210）/A（254） is an important parameter which could be used to estimate the DOM proportions of functional groups and conjugated carbon *** study provided also an understanding of stormwater quality constituents through assessing variability and sensitivity for various parameters,and the additional information of rainfall characteristics on runoff quality data for a better understanding of parameter correlations and influences.

关键词： Stormwater Dissolved organic matter HPSEC

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