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Implanting 1.1B4 human β-cell pseudoislets improves glycaemic control in diabetic severe combined immune deficient mice

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World Journal of diabetes 2016年第19期7卷 523-533页

作者： alastair d green Srividya Vasu Neville H McClenaghan Peter R Flatt SAAd Centre for Pharmacy and diabetes University of Ulster Cell Growth and Metabolism Section National Institute for Diabetes and Digestive and Kidney diseasesNational Institutes of Health

AIM To investigate the potential of implanting pseudoislets formed from human insulin-releasing β-cell lines as an alternative to islet transplantation. METHOdS In this study, the anti-diabetic potential of novel human insulin releasing 1.1B4 β-cells was evaluated by implanting the cells, either as free cell suspensions, or as three-dimensional pseudoislets, into the subscapular region of severe combined immune deficient mice rendered diabetic by single high-dose administration of streptozotocin. Metabolic parameters including food and fluid intake, bodyweight and blood glucose were monitored throughout the study. At the end of the study animals were given an intraperitoneal glucosetolerance test. Animals were then culled and blood and tissues were collected for analysis. Insulin and glucagon contents of plasma and tissues were measured by insulin radioimmunoassay and chemiluminescent enzyme-linked immunosorbance assay respectively. Histological analyses of pancreatic islets were carried out by quantitative fluorescence immunohistochemistry staining. RESULTS Both pseudoislet and cell suspension implants yielded well vascularised β-cell masses of similar insulin content. This was associated with progressive amelioration of hyperphagia(P dipsia(P dy weight loss(P d glucose tolerance(P d in both groups of transplanted mice, with increased β-cell(P d decreased alpha cell(P d hypoglycaemic complications, pseudoislet recipients displayed a more gradual amelioration of diabetes, and achieved stable blood glucose control similar to non-diabetic mice at the end of the study. CONCLUSION Although further work is needed to address safety issues, these results provide proof of concept for possible therapeutic applica

关键词： Human β-cell line 1.1B4 Cell therapy Insulin Pseudoislets

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Anti-N-methyl-d-aspartate receptor-associated encephalitis: A review of clinicopathologic hallmarks and multimodal imaging manifestations

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World Journal of Radiology 2024年第1期16卷 1-8页

作者： Bryce david Beutler alastair E Moody Jerry Mathew Thomas Benjamin Phillip Sugar Mark B Ulanja daniel Antwi-Amoabeng Lucas Anthony Tsikitas department of Radiology University of Southern CaliforniaKeck School of MedicineLos AngelesCA 90033United States department of Anesthesiology University of UtahSalt Lake CityUT 84132United States department of Internal Medicine Christus Ochsner St.Patrick HospitalLake CharlesLA 70601United States

Anti-N-methyl-d-aspartate receptor-associated encephalitis(NMdARE)is a rare immune-mediated neuroinflammatory condition characterized by the rapid onset of neuropsychiatric symptoms and autonomic *** mechanism of pathogenesis remains incompletely understood,but is thought to be related to antibodies targeting the GluN1 subunit of the NMdA receptor with resultant downstream dysregulation of dopaminergic *** adults are most frequently affected;the median age at diagnosis is 21 *** is a strong female predilection with a female sex predominance of 4:*** often develops as a paraneoplastic process and is most commonly associated with ovarian ***,NMdARE has also been described in patients with small cell lung cancer,clear cell renal carcinoma,and other benign and malignant *** is based on correlation of the clinical presentation,electro-encephalography,laboratory studies,and *** tomography,positron emission tomography,and magnetic resonance imaging are essential to identify an underlying tumor,exclude clinicopathologic mimics,and predict the likelihood of long-term functional *** imaging may be of value for prognostication and to assess the response to *** may involve high-dose corticosteroids,intravenous immunoglobulin,and plasma ***,we review the hallmark clinicopathologic features and imaging findings of this rare but potentially devastating condition and summarize diagnostic criteria,treatment regimens,and proposed pathogenetic mechanisms.

关键词： Anti-N-methyl-d-aspartate receptor-associated encephalitis Autoimmune encephalitis Encephalitis Ovarian teratoma Paraneoplastic syndrome Teratoma

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Interaction of Waves, Surface Currents, and Turbulence: the Application of Surface-Following Coordinate Systems

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Journal of Ocean University of China 2007年第4期6卷 319-331页

作者： Jenkins alastair d Bjerknes Centre for Climate Research Geophysical Institute Allegaten 70 N-5007 Bergen Norway

Surface waves comprise an important aspect of the interaction between the atmosphere and the ocean, so a dynamically consistent framework for modelling atmosphere-ocean interaction must take account of surface waves, either implicitly or explicitly. In order to calculate the effect of wind forcing on waves and currents, and vice versa, it is necessary to employ a consistent formula- tion of the energy and momentum balance within the airflow, wave field, and water column. It is very advantageous to apply sur- face-following coordinate systems, whereby the steep gradients in mean flow properties near the air-water interface in the cross-interface direction may be resolved over distances which are much smaller than the height of the waves themselves. We may account for the waves explicitly by employing a numerical spectral wave model, and applying a suitable theory of wave–mean flow interaction. If the mean flow is small compared with the wave phase speed, perturbation expansions of the hydrodynamic equations in a Lagrangian or generalized Lagrangian mean framework are useful: for stronger flows, such as for wind blowing over waves, the presence of critical levels where the mean flow velocity is equal to the wave phase speed necessitates the application of more general types of surface-following coordinate system. The interaction of the flow of air and water and associated differences in temperature and the concentration of various substances (such as gas species) gives rise to a complex boundary-layer structure at a wide range of vertical scales, from the sub-millimetre scales of gaseous diffusion, to several tens of metres for the turbulent Ekman layer. The bal- ance of momentum, heat, and mass is also affected significantly by breaking waves, which act to increase the effective area of the surface for mass transfer, and increase turbulent diffusive fluxes via the conversion of wave energy to turbulent kinetic energy.

关键词： wind-wave-current interaction coordinate systems upper-ocean turbulence air-sea exchange of momentum, heat, andmass

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Management of hypertension in COVId-19

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World Journal of Cardiology 2020年第5期12卷 228-230页

作者： daniel Antwi-Amoabeng Bryce d Beutler alastair E Moody Zahara Kanji Nageshwara Gullapalli Christopher J Rowan department of Internal Medicine Reno School of MedicineUniversity of NevadaRenoNV 89052United States department of Anesthesiology University of UtahSalt Lake CityUT 84132United States Renown Institute for Heart and Vascular Health RenoNV 89512United States

The ACE2 receptor plays a central role in severe acute respiratory syndrome coronavirus 2 host cell entry and *** has therefore been postulated that angiotensin converting enzyme inhibitors and angiotensin receptor blockers may upregulate ACE2 expression and thus increase susceptibility to *** suggest that alternative anti-hypertensive agents should be preferred among individuals who may be exposed to this increasingly common and potentially lethal virus.

关键词： Angiotensin converting enzyme inhibitor Angiotensin receptor blocker Carvedilol Coronavirus disease-19 COVId-19 SARS-CoV-2 Verapamil

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On the Validity of the Imbert-Fick Law: Mathematical Modelling of Eye Pressure Measurement

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World Journal of Mechanics 2016年第3期6卷 35-51页

作者： Gabriela González Castro alastair d. Fitt John Sweeney IRC in Polymer Science and Technology University of Bradford Bradford UK Oxford Brookes University Oxford UK

Ophthalmologists rely on a device known as the Goldmann applanation tonometer to make intraocular pressure (IOP) measurements. It measures the force required to press a flat disc against the cornea to produce a flattened circular region of known area. The IOP is deduced from this force using the Imbert-Fick principle. However, there is scant analytical justification for this analysis. We present a mathematical model of tonometry to investigate the relationship between the pressure derived by tonometry and the IOP. An elementary equilibrium analysis suggests that there is no physical basis for traditional tonometric analysis. Tonometry is modelled using a hollow spherical shell of solid material enclosing an elastic liquid core, with the shell in tension and the core under pressure. The shell is pressed against a rigid flat plane. The solution is found using finite element analysis. The shell material is anisotropic. Values for its elastic constants are obtained from literature except where data are unavailable, when reasonable limits are explored. The results show that the force measured by the Goldmann tonometer depends on the elastic constant values. The relationship between the IOP and the tonometer readings is complex, showing potentially high levels of inaccuracy that depend on IOP.

关键词： Tonometry Finite Element Analysis Imbert-Fick Law

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The effect of tailing lipidation on the bioactivity of antimicrobial peptides and their aggregation tendency Special Issue:Emerging Investigators

聚集体(英文)

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聚集体(英文) 2023年第4期4卷 195-209页

作者： Bruce Lin Andrew Hung William Singleton Kevion K.darmawan Rachael Moses Bicheng Yao Hongkang Wu Anders Barlow Marc-Antoine Sani alastair J.Sloan Mohammed Akhter Hossain John d.Wade Yuning Hong Neil M.O’Brien-Simpson Wenyi Li The Bio21 Institute of Molecular Science and Biotechnology University of MelbourneMelbourneVictoriaAustralia ACTV Research group Melbourne Dental SchoolCentre for Oral Health ResearchUniversity of MelbourneMelbourneVictoriaAustralia School of Science RMIT UniversityMelbourneVictoriaAustralia Melbourne dental School Division of Basic and Clinical Oral SciencesUniversity of MelbourneMelbourneVictoriaAustralia department of Biochemistry and Chemistry La Trobe Institute for Molecular ScienceLa Trobe UniversityMelbourneVictoriaAustralia Florey Institute of Neuroscience and Mental Health University of MelbourneMelbourneVictoriaAustralia School of Chemistry University of MelbourneMelbourneVictoriaAustralia Materials Characterisation and Fabrication Platform University of MelbourneMelbourneVictoriaAustralia

Antimicrobial peptides(AMPs)are potentially powerful alternatives to conven-tional antibiotics in combating multidrug resistance,given their broad spectrum of *** mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structures,resulting in permeability and destruction of target microorganism *** earlier work showed that two leading AMPs,MSI-78(4–20)and pardaxin(1–22),had potent antimicrobial activ-ity against a range of *** is known that the attachment of moderate-length lipid carbon chains to cationic peptides can further improve the functionality of these peptides through enhanced interactions with the membrane lipid bilayer,inducing membrane curvature,destabilization,and potential ***,in this work,we aimed to investigate the antimicrobial activity,oligomerization propensity,and lipid-membrane binding interactions of a range of N-terminal lipidated analogs of MSI-78(4–20)and pardaxin(1–22).Molecular modeling results suggest that aggregation of the N-lipidated AMPs may impart greater structural stability to the peptides in solu-tion and a greater depth of lipid bilayer insertion for the N-lipidated AMPs over the parental *** experimental and computationalfindings provide insights into how N-terminal lipidation of AMPs may alter their conformations,with subsequent effects on their functional properties in regard to their self-aggregation behavior,membrane interactions,and antimicrobial activity.

关键词： aggregation antimicrobial peptide lipidation membrane active peptide

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Methane Emissions from Grazing Holstein-Friesian Heifers at different Ages Estimated Using the Sulfur Hexafluoride Tracer Technique

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Engineering 2017年第5期3卷 753-759页

作者： Steven J. Morrisonn Judith McBride Alan W. Gordon alastair R. G. Wylie Tianhai Yan Agri-Food and Biosciences Institute Hillsborough County Down BT26 6DR UK Agri-Food and Biosciences Institute Belfast BT9 5PX UK

Although the effect of animal and diet factors on enteric methane （CH4） emissions from confined cattle has been extensively examined, less data is available regarding CH4 emissions from grazing young cattle. A study was undertaken to evaluate the effect of the physiological state of Holstein-Friesian heifers on their enteric CH4 emissions while grazing a perennial ryegrass sward. Two experiments were conducted： Experiment 1 ran from May 2011 for 11 weeks and Experiment 2 ran from August 2011 for 10 weeks. In each experiment, Holstein-Friesian heifers were divided into three treatment groups （12 animals/group） consisting of calves, yearling heifers, and in-calf heifers （average ages： 8.5, 14.5, and 20.5 months, respectively）. Methane emissions were estimated for each animal in the final week of each experiment using the sulfur hexafluoride tracer technique. dry matter （dM） intake was estimated using the calculated metabolizable energy （ME） requirement divided by the ME concentration in the grazed grass. As expected, live weight increased with increasing animal age （P 〈 0.001）; however, there was no difference in live weight gain among the three groups in Experiment 1, although in Experiment 2, this variable decreased with increasing animal age （P 〈 0.001 ）. In Experiment 1, yearling heifers had the highest CH4 emissions （g·d^-1） and in-calf heifers produced more than calves （P 〈 0.001 ）. When expressed as CH4 emissions per unit of live weight, dM intake, and gross energy （GE） intake, yearling heifers had higher emission rates than calves and in-calf heifers （P 〈 0.001）. However, the effects on CH4 emissions were different in Experiment 2, in which CH, emissions （g·d^-1） increased linearly with increasing animal age （P 〈 0.001）, although the difference between yearling and in-calf heifers was not significant. The CH4/live weight ratio was lower in in-calf heifers than in the other two groups （P 〈 0.001 ）, while CH4 energy output as a proportion of GE intake was lower

关键词： Methane emission Grazing dairy heifer Prediction Sulfur hexafluoride tracer technique

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Redefinition of Fatty Liver disease from NAFLd to MAFLd through the Lens of drug development and Regulatory Science

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Journal of Clinical and Translational Hepatology 2022年第2期10卷 374-382页

作者： Yasser Fouad Melissa Palmer Minjun Chen Arie Regev Rajarshi Banerjee Rob Myers Robert Riccio Richard Torstenson Ramy Younes Puneet SArora Henrik Landgren Morten A.Karsdal Martin Blake david A.Shapiro Hans-Juergen Gruss Muhammad Y.Sheikh dina Attia Steven Bollipo alastair d.Smith Bradley Freilich Robert G.Gish detlef Schuppan department of Gastroenterology Hepatologyand Endemic MedicineFaculty of MedicineMinia UniversityMiniaEgypt Gan-nex/Ascletis Pharma Co Ltd BeijingChina Liver Consulting LLC New YorkNYUSA division of Bioinformatics and Biostatis-tics National Center for Toxicological ResearchUS Food and Drug AdministrationJeffersonARUSA Eli Lilly and Company IndianapolisINUSA Perspectum diagnostics Ltd OxfordUK Gilead Sciences Inc Foster CityCAUSA Syneos Health LLC MorrisvilleNCUSA Allergan Marlow International BuckinghamshireUKAstraZenecaCambridgeUK Boehringer Ingel-heim International GmbHIngelheimGermany Genentech IncSouth San FranciscoCAUSA AbbVie MarlowBuck-inghamshireUK Nordic Bioscience A/S HerlevDenmark Resonance Health BurswoodWAAustralia Intercept Phar-maceuticals Inc San DiegoCAUSA Fresno Clinical Research Center FresnoCAUSA Gastroenterology and Hepatology department Beni-Suef UniversityBeni SuefEgypt department of Gastroenterology and Endoscopy John Hunter HospitalNewcastleNSWAustralia School of Medicine and Public Health University of NewcastleNewcastleNSWAustralia Kan-sas City Research Institute Kansas CityMOUSA division of Gastroenterology and Hepatology Loma Linda UniversityLoma LindaCAUSA Institute of Translational Immunology and Research Center for Immune Therapy University Medical CenterMainzGermany division of Gastroenterology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA

Metabolic(dysfunction)-associated fatty liver disease(MAFLd)affects a third of the population and is a leading cause of liver-related *** no effective treatments exist,novel approaches to drug development are ***,outdated terminology and definitions of the disease are hampering efforts to develop new drugs and *** international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease(NAFLd)to MAFLd,includ-ing a proposal for how the disease should be *** allies with the many stakeholders in MAFLd care―including patients,patients’advocates,clinicians,researchers,nurse and allied health groups,regional societies,and others―we are aware of the negative consequences of the NAFLd term and *** share the sense of urgency for change and will act in new ways to achieve our *** there is much work to be done to overcome clinical inertia and reverse worrisome recent trends,the MAFLd initiative provides a firm foundation to build *** provides a roadmap for moving for-ward toward more efficient care and affordable,sustainable drug and device innovation in MAFLd *** hope it will bring promising new opportunities for a brighter future for MAFLd care and improve care and outcomes for patients of one of the globe’s largest and costliest public health *** this viewpoint,we have revisited this initiative through the perspectives of drug development and regulatory science.

关键词： NAFLd MAFLd NASH Fatty liver disease Liver Fibrosis

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α受体阻滞剂对于输尿管支架管引起不适的治疗作用的荟萃分析

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中华泌尿外科杂志 2012年第9期33卷 654-654页

作者： alastair d( et al.) 席志军(摘译)

输尿管支架管留置可以引起患者明显不适，主要町能是由于输尿管平滑肌的痉挛和三角区的刺激。α受体阻滞剂可以减少平滑肌的活动，并且已经广泛地用于输尿管结石的排石治疗。

关键词：输尿管支架管 α受体阻滞剂荟萃分析治疗作用不适输尿管平滑肌支架管留置输尿管结石

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儿童急性咳嗽

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英国医学杂志中文版 2004年第5期7卷 314-315页

作者： alastair d Hay Knut Schroeder Tom Fahey 赵长安 division of Primary Health Care University of Bristol Bristol BS6 6JL clinical lecturer in primary health care Tayside Centre for General Practice University of Dundee Dundee DD2 4AD professor of primary care medicine

2月份，一位母亲带着她2岁的男孩来到诊所。患儿有进行性加剧的咳嗽、发热以及流涕等症状已10天。平时身体健康，但他的父母均患哮喘，因此其母亲担心他也可能患上哮喘。

关键词：咳嗽哮喘急性进行性流涕儿童诊所母亲父母男孩

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