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Molecular basis of inherited calcium channelopathies:role of mutations in pore-forming subunits

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Acta Pharmacologica Sinica 2006年第7期27卷 799-812页

作者： Lynn MCKEOWN Philip ROBIN owen T JONES Faculty of Life Sciences the University of ManchesterManchesterUK

The pore-forming alpha subunits of voltage-gated calcium channels contain theessential biophysical machinery that underlies calcium influx in response to *** combination with requisite auxiliary subunits,these pore sub-units form calcium channel complexes that are pivotal to the physiology andpharmacology of diverse cells ranging from sperm to *** surprisingly,mutations in the pore subunits generate diverse pathologies,termedchannelopathies,that range from failures in excitation-contraction coupling tonight *** the last decade,major insights into the mechanisms ofpathogenesis have been derived from animals showing spontaneous or *** parallel,there has been considerable growth in our understandingof the workings of voltage-gated ion channels from a structure-function,regula-tion and cell biology *** we document our current understandingof the mutations underlying channelopathies involving the voltage-gated calciumchannel alpha subunits in humans and other species.

关键词： calcium channels channelopathies mutation

Chain-to-Chain Competition Under Demand Uncertainty

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Journal of the Operations Research Society of China 2016年第1期4卷 49-75页

作者： owen Q.Wu Hong Chen Kelley School of Business Indiana UniversityBloomingtonINUSA Shanghai Advanced Institute of Finance Shanghai 200030China

In this paper,we aim to study the structure choice of supply chains under competitive environment with uncertain *** consider two competing supply chains,each of which chooses to either vertically integrate or decentralize with coordinating *** first analyze firms’strategic behavior under given supply chain structures:two integrated chains(II),two decentralized chains(DD),and a mixed structure with one decentralized chain and one integrated *** then compare different supply chain structures and examine the equilibrium structure *** find that the equilibrium structure depends on the product *** substitutable products,DD is the equilibrium supply chain structure choice,whereas for complementary products,II is the equilibrium ***,a high demand uncertainty strengthens these equilibrium choices.

关键词： coordination Chain-to-chain competition Demand unce

SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation

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World Journal of Transplantation 2024年第3期14卷 132-143页

作者： Amr Alnagar Nekisa Zakeri Konstantinos Koilias Rosemary E Faulkes Rachel Brown owen Cain M Thamara P R Perera Keith J Roberts Rebeca Sanabria-Mateos David C Bartlett Yuk Ting Ma Shivan Sivakumar Shishir Shetty Tahir Shah Bobby V M Dasari Department of HBP and Liver Transplantation Surgery Queen Elizabeth HospitalUniversity Hospitals BirminghamBirmingham B152GWUnited Kingdom Centre for Liver Research Institute of Biomedical ResearchBirmingham B152TTUnited Kingdom Department of Hepatology Queen Elizabeth HospitalUniversity Hospitals BirminghamBirmingham B152GWUnited Kingdom Department of Pathology University Hospitals Birmingham NHS Foundation TrustBirmingham B152GWUnited Kingdom Department of Oncology Queen Elizabeth HospitalUniversity Hospitals of BirminghamBirmingham B152GWUnited Kingdom

BACKGROUND Recurrence of hepatocellular carcinoma(HCC)following liver transplantation(LT)has a devastating influence on recipients’survival;however,the risk of recur-rence is not routinely *** stratification is vital with a long LT waiting time,as that could influence the recurrence despite strict listing *** This study aims to identify predictors of recurrence and develop a novel risk pre-diction score to forecast HCC recurrence following *** A retrospective review of LT for HCC recipients at University Hospitals Bir-mingham between July 2011 and February *** and multivariate analyses were performed to identify recurrence predictors,based on which the novel SIMAP500(satellite nodules,increase in size,microvascular invasion,AFP>500,poor differentiation)risk score was *** 234 LTs for HCC were performed with a median follow-up of 5.3 *** developed in 25 patients(10.7%).On univariate analyses,RETREAT score>3,α-fetoprotein(AFP)at listing 100-500 and>500,bridging,increased tumour size between imaging at the listing time and explant histology,increase in the size of viable tumour between listing and explant,presence of satellite nodules,micro-and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence,based on which,the SIMAP500 risk score is *** SIMAP500 demonstrated an excellent predictive ability(c-index=0.803)and outper-formed the RETREAT score(c-index=0.73).SIMAP500 is indicative of the time to disease *** SIMAP500 risk score identifies the LT recipients at risk of HCC *** stratification allows patient-centric post-transplant surveillance *** validation of the score is recommended.

关键词： Liver transplantation Hepatocellular carcinoma Recurrence Survival

Minor fibrillar collagens,variable regions alternative splicing,intrinsic disorder,and tyrosine sulfation

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Protein & Cell 2012年第6期3卷 419-433页

作者： Ming Fang Reed Jacob owen McDougal Julia Thom Oxford Department of Biological Sciences Boise State UniversityBoiseID 83725USA Department of Chemistry and Biochemistry Boise State UniversityBoiseID 83725USA Biomolecular Research Center Boise State UniversityBoiseID 83725USA

Minor fibrillar collagen types V and XI,are those less abundant than the fibrillar collagen types I,II and *** alpha chains share a high degree of similarity with respect to protein sequence in all domains except the variable *** variation and,in some cases,extensive alternative splicing contribute to the unique sequence characteristics of the variable *** unique expression patterns in tissues exist,the functions and biological relevance of the variable regions have not been *** this review,we summarize the existing knowledge about expression patterns and biological functions of the collagen types V and XI alpha *** of biochemical similarities among the peptides encoded by each exon of the variable region suggests the potential for a shared *** alternative splicing,conservation of biochemical characteristics in light of low sequence conservation,and evidence for intrinsic disorder,suggest modulation of binding events between the surface of collagen fibrils and surrounding extracellular molecules as a shared function.

关键词： minor fibrillar collagens variable regions alternative splicing fibrillogenesis heparan sulfate binding sites intrinsic disorder tyrosine sulfation

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Philosophy and Science Dialogue： Consciousness

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Frontiers of Philosophy in China 2018年第3期13卷 332-348页

作者： Giulio Tononi owen Flanagan School of Medicine Department of Psychiatry University of Wisconsin-Madison MadisonWI 53719 USA Department of Philosophy Duke University Durham NC 27708 USA

This is a dialogue between scientific explanation of consciousness. a philosopher and a scientist about the What is consciousness？ Does it admit of scientific explanation？ If so, what must a scientific theory of consciousness be like in order to provide us with a satisfying explanation of its explanandum？ And what types of entities might such a theory acknowledge as being conscious？ Philosopher owen Flanagan and scientist Giulio Tononi weigh in on these issues during an exchange about the nature and scientific explanation of consciousness.

关键词： consciousness integrated information theory phenomenology hard problem of consciousness scientific explanation

Alum split applications strengthened phosphorus fixation and phosphate sorption in high legacy phosphorus calcareous soil

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Journal of Environmental Sciences 2021年第3期33卷 87-97页

作者： Bingqian Fan owen Fenton Karen Daly Jiahui Ding Shuo Chen Qing Chen Beijing Key Laboratory of Farmyard Soil Pollution Prevention-control and Remediation College of Resources and Environmental SciencesChina Agricultural UniversityBeijing 100193China Teagasc Environmental Research CentreJohnstown CastleCo.WexfordIreland

High phosphorus(P)saturation arising from historic P inputs to protected vegetable fields(PVFs)drives high P mobilisation to *** of soils with alum has shown potential in terms of fixing labile P and protecting water *** present 15 month pot experiment investigated P stabilisation across single alum application(Alum-1 treatment,20 g alum/kg soil incorporated into soil before the maize was sown),alum split applications(Alum-4 treatment,5 g alum/kg soil incorporated into soil before each crop was sown i.e.4×5 g/kg)and soil only treatment(Control).Results showed that the Alum-1 treatment caused the strongest stabilisation of soil labile P after maize plant removal,whereas the P stabilisation effect was gradually weakened due to the transformation of soil non-labile P to labile P and the reduced active Al^(3+)in soil *** the Alum-4 treatment,soil labile P decreased gradually with each crop planting and was lower than the Alum-1 treatment at the end of the final crop removal,without any impairment on plant *** better P stabilisation at the end of Alum-4 treatment was closely correlated with a progressive supply of Al^(3+)and a gradual decrease of pH,which resulted in higher contents of poorlycrystalline Al,Fe and exchangeable *** aspects were conducive to increasing the soil P stabilisation and phosphate *** terms of management,growers in continuous cropping systems could utilise split alum applications as a strategy to alleviate P losses in high-P enriched calcareous soil.

关键词： High legacy phosphorus Calcareous soil Phosphorus stabilisation Alum split applications Non-crystalline Fe/Al

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Theoretical modelling of hot gas ingestion through turbine rim seals

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Propulsion and Power Research 2012年第1期1卷 1-11页

作者： J.Michael owen Department of Mechanical Engineering University of BathBath BA27AYUK

The rim seals of gas turbines are used to prevent or reduce the ingestion of hot mainstream gas into the wheel-space between the turbine rotor and its adjacent stationary *** ingestion is caused by local pressure differences between the mainstream and the wheel-space;ingress usually occurs where the mainstream pressure is higher than that in the wheel-space and egress occurs where it is *** air,which is supplied to the wheel-space,flows through the seal clearance and joins the mainstream *** much sealing air is inefficient;too little can lead to disastrous *** nozzle guide vanes create three-dimensional(3D)variations in the distribution of pressure in the mainstream annulus and the turbine blades create unsteady *** fluid dynamics(CFD)is both time-consuming and expensive for these 3D unsteady flows,and engine designers tend to use correlations or simple models to predict *** paper describes the application of simple‘orifice models’,the analytical solutions of which can be used to calculate the sealing effectiveness of turbine rim *** solutions agree well with available data for externally-induced ingress,where the effects of rotation are negligible,for rotationally-induced ingress,where the effects of the external flow are small,and for combined ingress,where the effects of both external flow and rotation are significant.

关键词： Gas turbine Rim seal Hot gas ingestion Orifice models Rotationally-induced ingress Externally-induced ingress

Lipid species dependent vesicles clustering caused by alpha-synuclein as revealed by single-vesicle imaging with total internal reflection fluorescence microscopy

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Biophysics Reports 2021年第6期7卷 437-448页

作者： Chinta Mani Aryal owen Tyoe Jiajie Diao Department of Cancer Biology University of Cincinnati College of Medicine Department of Physics University of Cincinnati

Single-molecule methods have been applied to study the mechanisms of many biophysical systems that occur on the nanometer scale. To probe the dynamics of such systems including vesicle docking, tethering, fusion, trafficking, protein-membrane interactions, etc., and to obtain reproducible experimental data; proper methodology and framework are crucial. Here, we address this need by developing a protocol for immobilization of vesicles composed of synthetic lipids and measurement using total internal reflection fluorescence(TIRF) microscopy. Furthermore, we demonstrate applications including vesicle clustering mediated by proteins such as alpha-Synuclein(αSyn) and the influence of external ions by using TIRF microscopy. Moreover, we use this method to quantify the dependence of lipid composition and charge on vesicle clustering mediated by αSyn which is based on the methods previously reported.

关键词： Single molecule Alpha-Synuclein Lipids Vesicles Clustering Total internal reflection fluorescence microscopy

Lipopolysaccharide inhibits or accelerates biomedical titanium corrosion depending on environmental acidity

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International Journal of Oral Science 2015年第3期7卷 179-186页

作者： Fei Yu owen Addison Stephen J Baker Alison J Davenport School of Metallurgy and Materials University of Birmingham Biomaterials Unit College of Medical and Dental Sciences University of Birmingham School of Geography Earth and Environmental Sciences University of Birmingham

Titanium and its alloys are routinely used as biomedical implants and are usually considered to be corrosion resistant under physiological conditions. However, during inflammation, chemical modifications of the peri-implant environment including acidification occur. In addition certain biomolecules including lipopolysaccharide（LPS）, a component of Gram-negative bacterial cell walls and driver of inflammation have been shown to interact strongly with Ti and modify its corrosion resistance. Gram-negative microbes are abundant in biofilms which form on dental implants. The objective was to investigate the influence of LPS on the corrosion properties of relevant biomedical Ti substrates as a function of environmental acidity. Inductively coupled plasma mass spectrometry was used to quantify Ti dissolution following immersion testing in physiological saline for three common biomedical grades of Ti（ASTM Grade 2, Grade 4 and Grade 5）. Complementary electrochemical tests including anodic and cathodic polarisation experiments and potentiostatic measurements were also conducted. All three Ti alloys were observed to behave similarly and ion release was sensitive to p H of the immersion solution. However, LPS significantly inhibited Ti release under the most acidic conditions（p H 2）, which may develop in localized corrosion sites, but promoted dissolution at p H 4–7, which would be more commonly encountered *** observed pattern of sensitivity to environmental acidity of the effect of LPS on Ti corrosion has not previously been reported. LPS is found extensively on the surfaces of skin and mucosal penetrating Ti implants and the findings are therefore relevant when considering the chemical stability of Ti implant surfaces in vivo.

关键词： corrosion electrochemistry inductively coupled plasma mass spectrometry lipopolysaccharide titanium

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