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Elucidating the Degradation Pathways of Hum.n 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.Batem.n Joseph P.O'Shea Abina m.Crean SSPC the SFI Centre for Pharmaceutical Research School of Pharmacy University College Cork School of Pharm.cy University College Cork Analytical and Biological Chem.stry Research Facility (ABCRF) University College Cork School of Chem.stry University College Cork

While there have been significant advances in the developm.nt of peptide oral dosage form. in recent years, highlighted by the clinical and com.ercial success of approved peptides such as Rybelsus?, there rem.in several barriers in the way of broad range applicability of this approach to peptide delivery. One such barrier includes the poor physical and chem.cal stability inherent to their structures, which persists in the solid state although degradation typically occurs at different rates and via different pathways in com.arison to the solution state. Using insulin as a m.del peptide, this work sought to contribute to the developm.nt of analytical techniques for investigating com.on insulin degradation pathways. Chem.cally denatured,deam.dated and aggregated sam.les were prepared and used to benchm.rk circular dichroism.spectroscopy, reverse phase HPLC and size exclusion chrom.tography m.thods for the investigation of unfolding, chem.cal m.difications and covalent aggregation of the insulin m.lecule respectively. Solid state degraded sam.les were prepared by heating insulin powder at 60 °C and 75% relative hum.dity for 1, 3, 5 and 7 d, and the degradation profiles of the sam.les were evaluated and com.ared with those observed in solution. While no unfolding was observed to occur, significant deam.dation 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 m.ans of assessing the m.chanism. of deam.dation and covalent aggregation occurring in the solid state.

关键词： Biopharm.ceutical analysis Covalent aggregation Deam.dation Disulfide cleavage Insulin Solid state Stability

Large quantum.alphabets with a tiny footprint

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Light(Science & Applications) 2024年第9期13卷 1701-1703页

作者： Fazilah Nothlawala andrew Forbes School of Physics University of the WitwatersrandJohannesburgSouth Africa

High-dim.nsional quantum.states are known to offer advantages over their two-dim.nsional qubit counterparts,but their preparation and m.nipulation has been bulky and ***,quantum.state control has been dem.nstrated on-chip with a~1μm. footprint and nm.scale features,producing up to eight-dim.nsional quantum.states and ushering in a new route to large quantum.inform.tion encoding on a sm.ll footprint.

关键词： quantum states dim.nsional

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 Departm.nt of m.them.tical 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 m.thod for studying rational superm.dules of the general linear supergroup GL(m.n).Furtherm.re,we establish a Schur-Weyl duality result for rational Schur superalgebras and conclude that under certain conditions these objects will be sem.sim.le.

关键词： Schur algebra superm.them.tics general linear supergroup

Particle Size Optim.zation of Therm.chem.cal Salt Hydrates for High Energy Density Therm.l Storage

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Energy & Environm.ntal m.terials 2024年第2期7卷 326-333页

作者： andrew m.rtin Drew Lilley Raνi Prasher Sum.njeet Kaur Energy Technologies Area Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Departm.nt of m.chanical Engineering UC BerkeleyBerkeleyCA 94720USA

Therm.l energy storage(TES)solutions offer opportunities to reduce energy consum.tion,greenhouse gas em.ssions,and ***,they can help reduce the peak load and address the interm.ttency of renewable energy sources by tim. shifting the load,which are critical toward zero energy *** m.terials(TCm.)as a class of TES undergo a solid-gas reversible chem.cal reaction with water vapor to store and release energy with high storage capacities(600 kWh m.(-3))and negligible self-discharge that m.kes them.uniquely suited as com.act,stand-alone units for daily or seasonal ***,TCm. suffer from.instabilities at the m.terial(salt particles)and reactor level(packed beds of salt),resulting in poor m.lti-cycle efficiency and high-levelized cost of *** this study,a m.del is developed to predict the pulverization lim.t or Rcrit of various salt hydrates during therm.l *** is critical as it provides design rules to m.ke m.chanically stable TCm.com.osites as well as enables the use of m.re energy-efficient m.nufacturing process(solid-state m.xing)to m.ke the *** m.del is experim.ntally validated on m.ltiple TCm.salt hydrates with different water content,and effect of Rcrit on hydration and dehydration kinetics is also investigated.

关键词： high energy density hydration kinetics long-term.cycling therm.l energy storage therm.chem.cal m.terials

Som. m.an Convergence Theorem. for the m.xim.m.of Norm.d Double Sum. of Banach Space Valued Random.Elem.nts

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Acta m.them.tica Sinica,English Series 2024年第7期40卷 1727-1740页

作者： andrew ROSALSKY Le Van THANH Nguyen Thi THUY Departm.nt of Statistics University of FloridaGainesvilleFL 32611-8545USA Departm.nt of m.them.tics Vinh UniversityVinhNghe AnViet Nam High School for Gifted Students Vinh UniversityVinhNghe AnViet Nam

In this correspondence,we establish m.an convergence theorem. for the m.xim.m.of norm.d double sum. of Banach space valued random.*** of the results pertain to random.elem.nts which are *** expand and im.rove a num.er of particular cases in the literature on m.an convergence of random.elem.nts in Banach *** of the m.in contributions of the paper is to sim.lify and im.rove a recent result of Li,Presnell,and Rosalsky[Journal of m.them.tical Inequalities,16,117–126(2022)].A new m.xim.l inequality for double sum. of m.dependent random.elem.nts is proved which m.y be of independent *** sharpness of the results is illustrated by four exam.les.

关键词： Double sum m.an convergence Radem.cher type p Banach space Banach space valued random.elem.nt m.dependent random.elem.nts

Carbon dioxide enrichm.nt affected flower num.ers transiently and increased successful post-pollination developm.nt stably but without altering final acorn production in m.ture 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 m.Clory Richard H.Ellis m.rtin Lukac Jo Clark Carolina m.yoral Kris m.Hart andrew R.G.Plackett A.Rob m.cKenzie 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 Birm.ngham.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 m.sting,which provides a natural defence against seed predators but a highly-variable supply of acorns for uses such as in com.ercial tree planting each *** em.ssions 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 *** exam.ne if acorn production in m.ture woodland com.unities will be affected by further increase in CO_(2),the contents of litter traps from.a Free Air Carbon Enrichm.nt(FACE)experim.nt in deciduous woodland in central England were analysed for num.ers of flowers and acorns of pedunculate oak(Quercus robur L.)at different stages of developm.nt and their predation levels under am.ient and elevated CO_(2) ***-annual variation in acorn num.ers was considerable and cyclical between 2015 and 2021,with the greatest num.ers of m.ture acorns in 2015,2017 and 2020 but alm.st none in *** num.ers of flowers,enlarged cups,im.ature acorns,em.ty acorn cups,and galls in the litter traps also varied am.ngst years;com.aratively high num.ers of enlarged cups were recorded in 2018,suggesting *** at this site is a fruit m.turation m.sting species(i.e.,the extent of abortion of pollinated flowers during acorn developm.nt affects m.ture acorn num.ers greatly).Raising the atm.spheric CO_(2) concentration by 150μL L^(−1),from.early 2017,increased the num.ers of im.ature acorns,and all acorn evidence(em.ty cups+im.ature acorns+m.ture acorns)detected in the litter traps com.ared to am.ient controls by 2021,but did not consistently affect the num.ers of flowers,enlarged cups,em.ty cups,or m.ture *** num.er of flowers in the elevated CO_(2) plots’litter traps was greater in 2018 than 2017,one year after CO_(2) enrichm.nt began,whereas num.ers declined in am.ient *** with CO_(2) also increased the num.er o

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

m.senchym.l stem.cell-based TRAIL delivery inhibits the m.tastatic state of clinical therapy-resistant progressive neuroblastom.

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

作者： Dinesh Babu Som.sundaram.andrew m.her Sheeja Aravindan Zhongxin Yu Brian m.esch Natarajan Aravindan Departm.nt of Radiation Oncology University of Oklahoma Health Sciences CenterOklahoma CityOKUSA Stephenson Cancer Center Oklahoma CityOKUSA Departm.nt 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 neuroblastom.s(pNBs)that defy current intensive m.ltim.dal clinical therapy(Im.T)are a significant contributor to overall childhood cancer deaths[l].Neuroblastom.s(NBs)that survive first-line Im.T actively evolve to acquire genetic and m.lecular rearrangem.nts and display unparalleled plasticity and evolution,which causes frequent relapses in a rapidly accelerating tim.line[2-4].

关键词： neuroblastom. clinical evolve

Biofabrication of nanocom.osite-based scaffolds containing hum.n bone extracellularm.trix for the differentiation of skeletal stem.and progenitor cells

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Bio-Design and m.nufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim.Janos m.Kanczler Stuart Lanham.andrew Rawlings m.rta Roldo Gianluca Tozzi Jonathan I.Dawson Gianluca Cidonio Richard O.C.Oreffo Faculty of m.dicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharm.cy and Biom.dical 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 m.tal im.lants are routinely used in skeletal ***,they fail to provide long-term.clinical resolution,necessitating a functional biom.m.tic tissue engineering *** use of native hum.n bone tissue for synthesizing a biom.m.ticm.terial inkfor three-dim.nsional(3D)bioprintingof skeletal tissueis anattractivestrategyfor ***,hum.n bone extracellular m.trix(bone-ECm.offers an exciting potential for the developm.nt of an appropriate m.croenvironm.nt for hum.n bone m.rrow strom.l cells(HBm.Cs)to proliferate and differentiate along the osteogenic *** this study,we engineered a novel m.terial ink(LAB)by blending hum.n bone-ECm.B)with nanoclay(L,Laponite®)and alginate(A)polym.rs using extrusion-based *** inclusion of the nanoﬁller and polym.ric m.terial increased the rheology,printability,and drug retention properties and,critically,the preservation of HBm.Cs viability upon *** com.osite of hum.n bone-ECm.based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after im.lantation in an ex vivo chick chorioallantoic m.m.rane(CAm.*** inclusion of bone m.rphogenetic protein-2(Bm.-2)with the HBm.Cs further enhanced vascularization and m.neralization after only seven *** study dem.nstrates the synergistic com.ination of nanoclay with biom.m.tic m.terials(alginate and bone-ECm.to support the form.tion of osteogenic tissue both in vitro and ex vivo and offers a prom.sing novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular m.trix Nanoclay Bone 3D bioprinting

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

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Cellular & m.lecular Im.unology 2024年第2期21卷 201-202页

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

Interleukin(IL)-37 is one of the few anti-inflam.atory m.m.ers of the predom.nantly pro-inflam.atory IL-1 cytokine ***-37 possesses alarm.n-like properties[1]and exerts its activities via intracellular[2]as well as cell surface receptor-dependent m.chanism.,and the latter involves IL-1R8 and IL-18Rα[3].Because of its powerful and broad-spectrum.peacem.king”[4]functions,considerable efforts have been invested in developing IL-37-based anti-inflam.atory therapeutics[5,6].

关键词： Interleukin neglected cytokine