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Elucidating the Degradation Pathways of Human Insulin in the Solid State

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Journal of Analysis and Testing 2024年第3期8卷 288-299页

作者： andrew Fagan Lorraine m.Bateman Joseph P.O'Shea Abina m.Crean SSPC the SFI Centre for Pharmaceutical Research School of Pharmacy University College Cork School of Pharmacy University College Cork Analytical and Biological Chemistry Research Facility (ABCRF) University College Cork School of Chemistry University College Cork

While there have been significant advances in the development of peptide oral dosage forms in recent years, highlighted by the clinical and commercial success of approved peptides such as Rybelsus?, there remain several barriers in the way of broad range applicability of this approach to peptide delivery. One such barrier includes the poor physical and chemical stability inherent to their structures, which persists in the solid state although degradation typically occurs at different rates and via different pathways in comparison to the solution state. Using insulin as a model peptide, this work sought to contribute to the development of analytical techniques for investigating common insulin degradation pathways. Chemically denatured,deamidated and aggregated samples were prepared and used to benchmark circular dichroism spectroscopy, reverse phase HPLC and size exclusion chromatography methods for the investigation of unfolding, chemical modifications and covalent aggregation of the insulin molecule respectively. Solid state degraded samples were prepared by heating insulin powder at 60 °C and 75% relative humidity for 1, 3, 5 and 7 d, and the degradation profiles of the samples were evaluated and compared with those observed in solution. While no unfolding was observed to occur, significant deamidation and covalent aggregation were detected. Reductive disulfide bond cleavage using dithiothreitol allowed for separation of the insulin A-and B-chains,offering a facile yet novel means of assessing the mechanisms of deamidation and covalent aggregation occurring in the solid state.

关键词： Biopharmaceutical analysis Covalent aggregation Deamidation Disulfide cleavage Insulin Solid state Stability

Rational Schur Superalgebras

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Algebra Colloquium 2024年第2期31卷 209-220页

作者： andrew Riesen Shun-Jen Cheng Department of mathematical and Statistical Sciences University of Alberta 1132489 Ave NWEdmontonAlbertaCanada 不详

We develop and study the generalization of rational Schur algebras to the super *** to the classical case,this provides a new method for studying rational supermodules of the general linear supergroup GL(m|n).Furthermore,we establish a Schur-Weyl duality result for rational Schur superalgebras and conclude that under certain conditions these objects will be semisimple.

关键词： Schur algebra supermathematics general linear supergroup

Some mean Convergence Theorems for the maximum of Normed Double Sums of Banach Space Valued Random Elements

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Acta mathematica Sinica,English Series 2024年第7期40卷 1727-1740页

作者： andrew ROSALSKY Le Van THANH Nguyen Thi THUY Department of Statistics University of FloridaGainesvilleFL 32611-8545USA Department of mathematics Vinh UniversityVinhNghe AnViet Nam High School for Gifted Students Vinh UniversityVinhNghe AnViet Nam

In this correspondence,we establish mean convergence theorems for the maximum of normed double sums of Banach space valued random *** of the results pertain to random elements which are *** expand and improve a number of particular cases in the literature on mean convergence of random elements in Banach *** of the main contributions of the paper is to simplify and improve a recent result of Li,Presnell,and Rosalsky[Journal of mathematical Inequalities,16,117–126(2022)].A new maximal inequality for double sums of m-dependent random elements is proved which may be of independent *** sharpness of the results is illustrated by four examples.

关键词： Double sum mean convergence Rademacher type p Banach space Banach space valued random element m-dependent random elements

Particle Size Optimization of Thermochemical Salt Hydrates for High Energy Density Thermal Storage

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Energy & Environmental materials 2024年第2期7卷 330-337页

作者： andrew martin Drew Lilley Raνi Prasher Sumanjeet Kaur Energy Technologies Area Lawrence Berkeley National Laboratory Department of mechanical Engineering UC Berkeley

Thermal energy storage（TES） solutions offer opportunities to reduce energy consumption, greenhouse gas emissions, and cost. Specifically, they can help reduce the peak load and address the intermittency of renewable energy sources by time shifting the load, which are critical toward zero energy buildings. Thermochemical materials（TCms） as a class of TES undergo a solid–gas reversible chemical reaction with water vapor to store and release energy with high storage capacities(600 k Wh m-3) and negligible selfdischarge that makes them uniquely suited as compact, stand-alone units for daily or seasonal storage. However, TCms suffer from instabilities at the material（salt particles） and reactor level（packed beds of salt）, resulting in poor multi-cycle efficiency and high-levelized cost of storage. In this study, a model is developed to predict the pulverization limit or Rcritof various salt hydrates during thermal cycling. This is critical as it provides design rules to make mechanically stable TCm composites as well as enables the use of more energy-efficient manufacturing process（solid-state mixing） to make the composites. The model is experimentally validated on multiple TCm salt hydrates with different water content, and effect of Rcriton hydration and dehydration kinetics is also investigated.

关键词： high energy density hydration kinetics long-term cycling thermal energy storage thermochemical materials

Carbon dioxide enrichment affected flower numbers transiently and increased successful post-pollination development stably but without altering final acorn production in mature pedunculate oak (Quercus robur L.)

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Journal of Forestry Research 2024年第4期35卷 1-12页

作者： Ryan mcClory Richard H.Ellis martin Lukac Jo Clark Carolina mayoral Kris m.Hart andrew R.G.Plackett A.Rob macKenzie School of Agriculture Policy and DevelopmentUniversity of ReadingAgricultureEarley GateWhiteknights RoadPO Box 237Reading RG66EUUK Faculty of Forestry and Wood Sciences Czech University of Life Sciences PraguePrague 165000Czechia Future Trees Trust Harwell Innovation CentreBuilding 173Curie AvenueHarwellOxford OX110QGUK Birmingham Institute of Forest Research University of BirminghamEdgbastonBirmingham B152TTUK School of Biosciences University of BirminghamEdgbastonBirmingham B152TTUK School of Geography Earth and Environmental SciencesUniversity of BirminghamEdgbastonBirmingham B152TTUK

Acorn production in oak(Quercus spp.)shows considerable inter-annual variation,known as masting,which provides a natural defence against seed predators but a highly-variable supply of acorns for uses such as in commercial tree planting each *** emissions of greenhouse gases have been very widely reported to influence plant growth and seed or fruit size and quantity via the‘fertilisation effect’that leads to enhanced *** examine if acorn production in mature woodland communities will be affected by further increase in CO_(2),the contents of litter traps from a Free Air Carbon Enrichment(FACE)experiment in deciduous woodland in central England were analysed for numbers of flowers and acorns of pedunculate oak(Quercus robur L.)at different stages of development and their predation levels under ambient and elevated CO_(2) ***-annual variation in acorn numbers was considerable and cyclical between 2015 and 2021,with the greatest numbers of mature acorns in 2015,2017 and 2020 but almost none in *** numbers of flowers,enlarged cups,immature acorns,empty acorn cups,and galls in the litter traps also varied amongst years;comparatively high numbers of enlarged cups were recorded in 2018,suggesting *** at this site is a fruit maturation masting species(i.e.,the extent of abortion of pollinated flowers during acorn development affects mature acorn numbers greatly).Raising the atmospheric CO_(2) concentration by 150μL L^(−1),from early 2017,increased the numbers of immature acorns,and all acorn evidence(empty cups+immature acorns+mature acorns)detected in the litter traps compared to ambient controls by 2021,but did not consistently affect the numbers of flowers,enlarged cups,empty cups,or mature *** number of flowers in the elevated CO_(2) plots’litter traps was greater in 2018 than 2017,one year after CO_(2) enrichment began,whereas numbers declined in ambient *** with CO_(2) also increased the number o

关键词： Quercus robur L. Acorns masting Pedunculate oak Carbon dioxide

mesenchymal stem cell-based TRAIL delivery inhibits the metastatic state of clinical therapy-resistant progressive neuroblastoma

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World Journal of Pediatrics 2024年第3期20卷 287-293页

作者： Dinesh Babu Somasundaram andrew maher Sheeja Aravindan Zhongxin Yu Brian mBesch Natarajan Aravindan Department of Radiation Oncology University of Oklahoma Health Sciences CenterOklahoma CityOKUSA Stephenson Cancer Center Oklahoma CityOKUSA Department of Pathology University of Oklahoma Health Sciences CenterOklahoma CityOKUSA Radiation Biology Laboratory University of Oklahoma Health Sciences CenterBSEB 302F941 Stanton L.Young BoulevardOklahoma CityOK 73104USA

Progressive neuroblastomas(pNBs)that defy current intensive multimodal clinical therapy(ImCT)are a significant contributor to overall childhood cancer deaths[l].Neuroblastomas(NBs)that survive first-line ImCT actively evolve to acquire genetic and molecular rearrangements and display unparalleled plasticity and evolution,which causes frequent relapses in a rapidly accelerating timeline[2-4].

关键词： neuroblastoma clinical evolve

Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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Bio-Design and manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim Janos m.Kanczler Stuart Lanham andrew Rawlings marta Roldo Gianluca Tozzi Jonathan I.Dawson Gianluca Cidonio Richard O.C.Oreffo Faculty of medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and Biomedical Science University of PortsmouthPortsmouth PO12DTUK School of Engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK Center for Life Nano-and Neuro-Science(CLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal ***,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering *** use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor ***,human bone extracellular matrix(bone-ECm)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBmSCs)to proliferate and differentiate along the osteogenic *** this study,we engineered a novel material ink(LAB)by blending human bone-ECm(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based *** inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBmSCs viability upon *** composite of human bone-ECm-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAm)*** inclusion of bone morphogenetic protein-2(BmP-2)with the HBmSCs further enhanced vascularization and mineralization after only seven *** study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECm)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay Bone 3D bioprinting

Thirteen years to get from b to a:one of the neglected isoforms of IL-37 enters the stage

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Cellular & molecular Immunology 2024年第2期21卷 201-202页

作者： Steven X.Cho Ina Rudloff andrew m.Ellisdon Claudia A.Nold-Petry marcel F.Nold Ritchie Centre Hudson Institute of Medical ResearchMelbourneVICAustralia Department of Pediatrics Monash UniversityMelbourneVICAustralia Cancer Program Biomedicine Discovery InstituteMonash UniversityMelbourneVICAustralia monash Newborn Monash Children’s HospitalMelbourneVICAustralia

Interleukin(IL)-37 is one of the few anti-inflammatory members of the predominantly pro-inflammatory IL-1 cytokine ***-37 possesses alarmin-like properties[1]and exerts its activities via intracellular[2]as well as cell surface receptor-dependent mechanisms,and the latter involves IL-1R8 and IL-18Rα[3].Because of its powerful and broad-spectrum“peacemaking”[4]functions,considerable efforts have been invested in developing IL-37-based anti-inflammatory therapeutics[5,6].

关键词： Interleukin neglected cytokine

Early anticoagulation in patients with stroke and atrial fibrillation is associated with fewer ischaemic lesions at 1 month: the ATTUNE study

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Stroke & Vascular Neurology 2024年第1期9卷 30-37,I0034页

作者： Angelos Sharobeam Longting Lin Christina Lam Carlos Garcia-Esperon Yash Gawarikar Ronak Patel matthew Lee-Archer andrew Wong michael Roizman Amanda Gilligan andrew Lee Kee meng Tan Susan Day Christopher Levi Stephen m Davis mark Parsons Bernard Yan melbourne Brain Centre at Royal melbourne Hospital ParkvilleVictoriaAustralia University of New South Wales South Western Sydney Clinical School LiverpoolNew South WalesAustralia Department of Neurology John Hunter HospitalNewcastleNew South WalesAustralia Department of Neurology Calvary Public HospitalCanberraAustralian Capital TerritoryAustralia Department of Neurology Northern Hospital EppingEppingVictoriaAustralia Department of Neurology Royal Brisbane and Women's HospitalHerstonQueenslandAustralia The University of Queensland School of medicine HerstonQueenslandAustralia Neurosciences Clinical Institute Epworth HealthcareRichmondVirginiaAustralia Department of Neurology Austin HealthUniversity of MelbourneHeidelbergVictoriaAustralia Flinders University College of medicine and Public Health AdelaideSouth AustraliaAustralia Department of Neurology Gold Coast University HospitalSouthportQueenslandAustralia The University of Sydney Northern Clinical School St LeonardsNew South WalesAustralia Department of Neurology and Neurophysiology Liverpool HospitalLiverpoolNew South WalesAustralia

Background The optimal time to commence anticoagulation in patients with atrial fibrillation(AF)after ischaemic stroke or transient ischaemic attack(TIA)is unclear,with guidelines differing in recommendations.A limitation of previous studies is the focus on clinically overt stroke,rather than radiologically obvious diffusion-weighted imaging ischaemic *** aimed to quantify silent ischaemic lesions and haemorrhages on mRI at 1month in patients commenced on early(mic lesions and more haemorrhages in the early anticoagulant group at 1-month *** A prospective multicentre,observational cohort study was performed at 11 Australian stroke *** and mRI data were collected at baseline and follow-up,with blinded imaging assessment performed by two *** of commencement of anticoagulation was at the discretion of the treating stroke *** We recruited 276 patients of whom 208 met the eligibility *** average age was 74.2 years(SD±10.63),and 79(38%)patients were *** National Institute of Health Stroke Scale score was 5(IQR 1–12).median baseline ischaemic lesion volume was 5mL(IQR 2–17).There were a greater number of new ischaemic lesions on follow-up mRI in patients commenced on anticoagulation≥4days after index event(17%vs 8%,p=0.04),but no difference in haemorrhage rates(22%vs 32%,p=0.10).Baseline ischaemic lesion volume of≤5mL was less likely to have a new haemorrhage at 1month(p=0.02).There was no difference in haemorrhage rates in patients with an initial ischaemic lesion volume of>5mL,regardless of anticoagulation *** Commencing anticoagulationmic lesions at 1month in AF *** is no increased rate of haemorrhage with early *** results suggest that early anticoagulation after mild-to-moderate acute ischaemic stroke associated w

关键词： patients lesions ischaemic