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molecular targets in the treatment of alcoholic hepatitis

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World Journal of Gastroenterology 2012年第39期18卷 5504-5513页

作者： Ashwin D Dhanda Richard WL Lee Peter L collins C anne mcCune Department of Liver medicine University Hospitals Bristol NHS Foundation TrustBS2 8HW BristolUnited Kingdom Department of Cellular and molecular medicine School of Clinical SciencesUniversity of BristolBS9 1TD BristolUnited Kingdom

Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, CXCL9 and CXCR3) and augmentation of anti-inflam- matory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease.

关键词： Alcoholic hepatitis Tumour necrosis factor-m Pentoxifylline Interleukins Chemokine receptors

An Efficient,Energy Stable Scheme for the Cahn-Hilliard-Brinkman System

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Communications in Computational Physics 2013年第4期13卷 929-957页

作者： Craig collins Jie Shen Steven m.Wise Department of mathematics University of TennesseeKnoxvilleTN 37912USA Department of mathematics Purdue UniversityWest LafayetteIN 47907USA

We present an unconditionally energy stable and uniquely solvable finite difference scheme for the Cahn-Hilliard-Brinkman(CHB)system,which is comprised of a Cahn-Hilliard-type diffusion equation and a generalized Brinkman equation modeling fluid *** CHB system is a generalization of the Cahn-Hilliard-Stokes model and describes two phase very viscous flows in porous *** scheme is based on a convex splitting of the discrete CH energy and is *** equations at the implicit time level are nonlinear,but we prove that they represent the gradient of a strictly convex functional and are therefore uniquely solvable,regardless of time step *** to energy stability,we show that the scheme is stable in the time and space discrete ℓ^(∞)(0,T;H_(h)^(1))and ℓ^(2)(0,T;H_(h)^(2))*** also present an efficient,practical nonlinear multigrid method–comprised of a standard FAS method for the Cahn-Hilliard part,and a method based on the Vanka smoothing strategy for the Brinkman part-for solving these *** particular,we provide evidence that the solver has nearly optimal complexity in typical *** solver is applied to simulate spinodal decomposition of a viscous fluid in a porous medium,as well as to the more general problems of buoyancy-and boundary-driven flows.

关键词： Cahn-Hilliard equation Stokes equations Brinkman equation finite difference methods nonlinear multigrid convex splitting energy stability

Late Neoproterozoic adakitic magmatism of the eastern Arabian Nubian Shield

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Geoscience Frontiers 2019年第6期10卷 1981-1992页

作者： Grant m.Cox John Foden Alan S.collins Centre for Tectonics Resources and Exploration(TRaX) Dept of Earth SciencesThe University of Adelaide

Late Neoproterozoic adakitic magmatism within the Eastern Arabian Nubian Shield has been dated at633.2±9.0 ma(2σ).These magnas intrude the forearc Ad Dawadimi Basin,which is composed of metapelitic schists and greywacke along with ophiolitic melanges of boninitic affinity which underwent inversion and deformation by^620 *** adakitic magmatism,while intruding parts of the Ad Dawadimi Basin,predates this deformation,but is possibly coincident with basin *** adakitic magmatism requires melting of an amphibolite or eclogitic source,empirical and experimental constraints require anomalously hot supra-subduction zone *** that this magmatism immediately predates basin inversion,these magmas possibly pinpoint the timing of the slab breaking,marking the terminal stages of arc magmatism,terrane accretion and the influx of hot oceanic asthenospheric *** influx of hot asthenospheric mantle may also be responsible for postcolltsional A-type magmatism.

关键词： Arabian Nubian Shield Adakites A-type magmatism

Two-dimensional discrete mathematical model of tumor-induced angiogenesis

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Applied mathematics and mechanics(English Edition) 2009年第4期30卷 455-462页

作者：赵改平陈二云吴洁许世雄 m.W.collins 龙泉 School of medical Instrument and Food Engineering University of Shanghai for Scienceand Technology School of Energy and Power Engineering University of Shanghai for Science and Technology Department of mechanics and Engineering Science Fudan University Brunel Institute for Bioengineering School of Engineering and DesignBrunel University

A 2D discrete mathematical model of a nine-point finite difference scheme is built to simulate tumor-induced angiogenesis. Nine motion directions of an individual endothelial cell and two parent vessels are extended in the present model. The process of tumor-induced angiogenesis is performed by coupling random motility, chemotaxis, and haptotaxis of endothelial cell in different mechanical environments inside and outside the tumor. The results show that nearly realistic tumor microvascular networks with neoplastic pathophysiological characteristics can be generated from the present model. moreover, the theoretical capillary networks generated in numerical simulations of the discrete model may provide useful information for further clinical research.

关键词： tumor angiogenesis discrete mathematical model nine-point scheme nu-merical simulation

Chest complications in autologous breast reconstruction

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Plastic and Aesthetic Research 2023年第1期10卷 205-215页

作者： Candice m.Leach meredith S.collins Department of Plastic and Reconstructive Surgery University of Kansas Medical CenterKansas CityKS 66160USA

Complications from autologous free flap reconstruction of the breast can present with both common surgical complications and unique complications at the chest recipient *** review covers complications at the chest recipient site,including chest wall deformity,chronic pain,mastectomy skin flap necrosis,infection,pyoderma gangrenosum,bleeding complications,pneumothorax,chyle leak,and positive internal mammary lymph node metastasis.

关键词： Autologous breast reconstruction complications chest wall deformity pneumothorax mastectomy skin flap necrosis chyle leak internal mammary node metastasis

The potential of bone morphogenetic protein 2 as a neurotrophic factor for Parkinson’s disease

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Neural Regeneration Research 2020年第8期15卷 1432-1436页

作者： Susan R.Goulding Aideen m.Sullivan Gerard W.O’Keeffe Louise m.collins Department of Biological Sciences Cork Institute of TechnologyCorkIreland Department of Anatomy and Neuroscience and Cork Neuroscience Centre University College CorkCorkIreland Department of Physiology University College CorkCorkIreland

Parkinson’s disease is the second most common neurodegenerative disorder;it affects 1%of the population over the age of *** number of people with Parkinson’s disease is set to rapidly increase due to changing demographics and there is an unmet clinical need for disease-modifying *** pathological hallmarks of Parkinson’s disease are the progressive degeneration of dopaminergic neurons in the substantia nigra and their axons which project to the striatum,and the aggregation ofα-synuclein;these result in a range of debilitating motor and non-motor *** application of neurotrophic factors to protect and potentially regenerate the remaining dopaminergic neurons is a major area of research ***,this strategy has had limited success to *** trials of two well-known neurotrophic factors,glial cell line-derived neurotrophic factor and neurturin,have reported limited efficacy in Parkinson’s disease patients,despite these factors showing potent neurotrophic actions in animal *** is therefore a need to identify other neurotrophic factors that can protect againstα-synuclein-induced degeneration of dopaminergic *** bone morphogenetic protein(BmP)family is the largest subgroup of the transforming growth factor-βsuperfamily of *** are naturally secreted proteins that play crucial roles throughout the developing nervous ***,many BmPs have been shown to be potent neurotrophic factors for dopaminergic *** we discuss recent work showing that transcripts for the BmP receptors and BmP2 are co-expressed with several key markers of dopaminergic neurons in the human substantia nigra,and evidence for downregulation of BmP2 expression at distinct stages of Parkinson’s *** also discuss studies that explored the effects of BmP2 treatment,in in vitro and in vivo models of Parkinson’s *** studies found potent effects of BmP2 on dopaminergic neurites,which is important given that axon deg

关键词： axon growth BmP2 dopaminergic neurons neuroprotection neurotrophic factor neuroregeneration Parkinson’s disease α-synuclein

Ultra-resolution scalable microprinting

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microsystems & Nanoengineering 2023年第3期9卷 195-207页

作者： Callum Vidler Kenneth Crozier David collins Department of Biomedical Engineering University of MelbourneMelbourneVICAustralia School of Physics University of MelbourneVictoria 3010Australia Department of Electrical and Electronic Engineering University of MelbourneVictoria 3010Australia Australian Research Council(ARC)Centre of Excellence for Transformative meta-Optical Systems University of MelbourneVictoria 3010Australia The Graeme Clark Institute The University of MelbourneParkville 3052 VICAustralia

Projection micro stereolithography(PµSL)is a digital light processing(DLP)based printing technique for producing structured *** this approach there is often a tradeoff between the largest object that can be printed and the minimum feature size,with higher resolution generally reducing the overall extent of the *** ability to produce structures with high spatial resolution and large overall volume,however,is immensely important for the creation of hierarchical materials,microfluidic devices and bioinspired *** this work,we report a low-cost system with 1µm optical resolution,representing the highest resolution system yet developed for the creation of micro-structured parts whose overall dimensions are nevertheless on the order of *** do so,we examine the limits at which PµSL can be applied at scale as a function of energy dosage,resin composition,cure depth and in-plane feature *** doing so we develop a unique exposure composition approach that allows us to greatly improve the resolution of printed *** ability to construct high-resolution scalable microstructures has the potential to accelerate advances in emerging areas,including 3D metamaterials,tissue engineering and bioinspired constructs.

关键词： lithography resolution printing

Growth differentiation factor 5:a neurotrophic factor with neuroprotective potential in Parkinson’s disease

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Neural Regeneration Research 2022年第1期17卷 38-44页

作者： Susan R.Goulding Jayanth Anantha Louise m.collins Aideen m.Sullivan Gerard W.O’Keeffe Department of Anatomy and Neuroscience and Cork Neuroscience CentreUniversity College CorkCorkIreland Department of Physiology University College CorkCorkIreland

Parkinson’s disease is the most common movement disorder worldwide,affecting over 6 million *** is an age-related disease,occurring in 1%of people over the age of 60,and 3%of the population over 80 *** disease is characterized by the progressive loss of midbrain dopaminergic neurons from the substantia nigra,and their axons,which innervate the striatum,resulting in the characteristic motor and non-motor symptoms of Parkinson’s *** is paralleled by the intracellular accumulation ofα-synuclein in several regions of the nervous *** therapies are solely symptomatic and do not stop or slow disease *** promising disease-modifying strategy to arrest the loss of dopaminergic neurons is the targeted delivery of neurotrophic factors to the substantia nigra or striatum,to protect the remaining dopaminergic neurons of the nigrostriatal ***,clinical trials of two well-established neurotrophic factors,glial cell line-derived neurotrophic factor and neurturin,have failed to meet their primary *** failure is thought to be at least partly due to the downregulation byα-synuclein of Ret,the common co-receptor of glial cell line-derived neurorophic factor and ***/differentiation factor 5 is a member of the bone morphogenetic protein family of neurotrophic factors,that signals through the Ret-independent canonical Smad signaling ***,we review the evidence for the neurotrophic potential of growth/differentiation factor 5 in in vitro and in vivo models of Parkinson’s *** discuss new work on growth/differentiation factor 5’s mechanisms of action,as well as data showing that viral delivery of growth/differentiation factor 5 to the substantia nigra is neuroprotective in theα-synuclein rat model of Parkinson’s *** data highlight the potential for growth/differentiation factor 5 as a disease-modifying therapy for Parkinson’s disease.

关键词： adeno-associated virus bone morphogenetic protein dopaminergic neurons growth/differentiation factor 5 neurodegeneration neuroprotection neurotrophic factor Parkinson’s disease Smad signaling α-synuclein

Prograde and retrograde growth of monazite in migmatites:An example from the Nagercoil Block,southern India

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Geoscience Frontiers 2015年第3期6卷 373-387页

作者： Tim E.Johnson Chris Clark Richard J.m.Taylor m.Santosh Alan S.collins Department of Applied Geology The Institute for Geoscience Research(TIGeR)Curtin University School of the Earth Sciences and Resources China University of Geosciences(Beijing) Tectonics Resources and Exploration(TRaX)Department of Earth SciencesUniversity of Adelaide

Data from a migmatised metapelite raft enclosed within charnockite provide quantitative constraints on the pressure-temperature-time （P-T-t） evolution of the Nagercoil Block at the southernmost tip of peninsular India. An inferred peak metamorphic assemblage of garnet, K-feldspar, sillimanite, plagioclase, magnetite, ilmenite, spinel and melt is consistent with peak metamorphic pressures of 6-8 kbar and temperatures in excess of 900 ℃. Subsequent growth of cordierite and biotite record high-temperature retrograde decompression to around 5 kbar and 800 ℃. SHRImP U-Pb dating of magmatic zircon cores suggests that the sedimentary protoliths were in part derived from felsic igneous rocks with Palae- oproterozoic crystallisation ages. New growth of metamorphic zircon on the rims of detrital grains constrains the onset of melt crystallisation, and the minimum age of the metamorphic peak, to around 560 ma. The data suggest two stages of monazite growth. The first generation of REE-enriched monazite grew during partial melting along the prograde path at around 570 ma via the incongruent breakdown of apatite. Relatively REE-depleted rims, which have a pronounced negative europium anomaly, grew during melt crystallisation along the retrograde path at around 535 ma. Our data show the rocks remained at suprasolidus temperatures for at least 35 million years and probably much longer, supporting a long-lived high-grade metamorphic history. The metamorphic conditions, timing and duration of the implied clockwise P-T-t path are similar to that previously established for other regions in peninsular India during the Ediacaran to Cambrian assembly of that part of the Gondwanan supercontinent.

关键词： monazire migmatite Zircon Geochronology Phase equilibria modelling Gondwana