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Elucidating the Degradation Pathways of Human Insulin in the Solid State

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 ResearchSchool of PharmacyUniversity College CorkCork T12 YT20Ireland School of Pharmacy University College CorkCork T12 YT20Ireland Analytical and Biological Chemistry Research Facility(ABCRF) University College CorkCork T12 YN60Ireland School of Chemistry University College CorkCork T12 YN60Ireland

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 *** 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 *** insulin as a model peptide,this work sought to contribute to the development of analytical techniques for investigating common insulin degradation *** 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 *** 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 *** no unfolding was observed to occur,significant deamidation and covalent aggregation were *** 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： Insulin Stability Solid state Deamidation Covalent aggregation Disulfide cleavage Biopharmaceutical analysis

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Examination of the molecular control of ruminal epithelial function in response to dietary restriction and subsequent compensatory growth in cattle

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Journal of Animal Science and Biotechnology 2017年第1期8卷 107-118页

作者： Emma O＇shea Sinead m. Waters Kate Keogh Alan K. Kelly David A. Kenny School of Agriculture and Food Science University College DublinBelfield Dublin 4Ireland Animal and Bioscience Research Department Animal & Grassland Research and Innovation Centre Teagasc Grange Dunsany Co Meath Ireland UCD Earth Institute University College Dublin Belfield Dublin 4 Ireland

Background： The objective of this study was to investigate the effect of dietary restriction and subsequent compensatory growth on the relative expression of genes involved in volatile fatty acid transport, metabolism and cell proliferation in ruminal epithelial tissue of beef cattle. Sixty Holstein Friesian bulls（mean liveweight 370 ± 35 kg;mean age 479 ± 15 d） were assigned to one of two groups：（i） restricted feed allowance（RES; n = 30） for 125 d（Period 1） followed by ad libitum access to feed for 55 d（Period 2） or（ii） ad libitum access to feed throughout（ADLIB; n = 30）. Target growth rate for RES was 0.6 kg/d during Period 1. At the end of each dietary period, 15 animals from each treatment group were slaughtered and ruminal epithelial tissue and liquid digesta harvested from the ventral sac of the rumen. Real-time q PCR was used to quantify m RNA transcripts of 26 genes associated with ruminal epithelial function. Volatile fatty acid analysis of rumen fluid from individual animals was conducted using gas ***： Diet × period interactions were evident for genes involved in ketogenesis（BDH2, P = 0.017）, pyruvate metabolism（LDHa, P = 0.048; PDHA1, P = 0.015） and cellular transport and structure（DSG1, P = 0.019; CACT, P = 0.027）. Ruminal concentrations of propionic acid（P = 0.018） and n-valeric acid（P = 0.029） were lower in RES animals, compared with ADLIB, throughout the experiment. There was also a strong tendency（P = 0.064）toward a diet × period interaction for n-butyric with higher concentrations in RES animals, compared with ADLIB, during Period ***： These data suggest that following nutrient restriction, the structural integrity of the rumen wall is compromised and there is upregulation of genes involved in the production of ketone bodies and breakdown of pyruvate for cellular energy. These results provide an insight into the potential molecular mechanisms regulating ruminal epithelial absorptive metabolism and growth following nutri

关键词： Beef cattle Compensatory growth Feed efficiency Nutrient restriction Rumen epithelium

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Optimization of micropatterned poly(lactic-coglycolic acid) films for enhancing dorsal root ganglion cell orientation and extension

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Neural Regeneration Research 2018年第1期13卷 105-111页

作者： Ching-Wen Li Brett Davis Jill shea Himanshu Sant Bruce Kent Gale Jayant Agarwal Department of mechanical Engineering National Chung Hsing University Department of Surgery School of Medicine University of Utah Department of mechanical Engineering University of Utah

Nerve conduits have been a viable alternative to the ‘gold standard’ autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffective in large gap injuries. Ridge/groove surface micropatterning has been shown to promote neural cell orientation and guide growth. However, optimization of the ratio of ridge/groove parameters to promote orientation and extension for dorsal root ganglion （DRG） cells on poly（lactic-co-glycolic acid）（PLGA） films has not been previously conducted. Photolithography and micro-molding were used to define various combinations of ridge/groove dimensions on PLGA films. The DRG cells obtained from chicken embryos were cultured on micropatterned PLGA films for cell orientation and migration *** of the films occurred during the test period, however, this did not cause deformation or distortion of the micropatterns. Results from the DRG cell orientation test suggest that when the ridge/groove ratio equals 1 （ridge/groove width parameters are equal, i.e., 10 μm/10 μm （even））, the degree of alignment depends on the size of the ridges and grooves, when the ratio is smaller than 1 （groove controlled） the alignment increases as the ridge size decreases, and when the ratio is larger than 1 （ridge controlled）, the alignment is reduced as the width of the grooves decreases. The migration rate and neurite extension of DRG neurons were greatest on 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films. Based on the data, the 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films are the optimized ridge/groove surface patterns for the construction of nerve repair devices.

关键词： nerve regeneration nerve repair neural cell migration neural cell alignment micropattern dorsal root ganglion topological cues neural regeneration

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Controlled release of FK506 from micropatterned PLGA films:potential for application in peripheral nerve repair

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Neural Regeneration Research 2018年第7期13卷 1247-1252页

作者： Brett Davis Susan Wojtalewicz Pratima Labroo Jill shea Himanshu Sant Bruce Gale Jayant Agarwal Department of Bioengineering University of Utah Department of Surgery University of Utah Department of mechanical Engineering University of Utah

After decades of research,peripheral nerve injury and repair still frequently results in paralysis,chronic pain and neuropathies leading to severe disability in *** clinically available nerve conduits only provide crude guidance of regenerating axons across nerve gap without additional ***506（Tacrolimus）,an FDA approved immunosuppressant,has been shown to enhance peripheral nerve regeneration but carries harsh side-effects when delivered *** objective of this study was to develop and evaluate a bioresorbable drug delivery system capable of local extended delivery of FK506 that also provides topological guidance cues to guide axon growth via *** was used to create micropatterned poly（lactide-co-glycolic acid）（PLGA） films embedded with ***-patterned,10/10 μm（ridge/groove width）,and 30/30 μm patterned films loaded with 0,1,and 3 μg/cm2 FK506 were manufactured and *** vitro FK506 rate of release testing indicated that the films are capable of an extended（at least 56 days）,controlled,and scalable release of *** extension bioactivity assay indicated that FK506 released from the films（concentration of samples tested ranged between 8.46–19.7 ng/m L） maintained its neural bioactivity and promoted neurite extension similar to control FK506 dosages（10 ng/m L FK506）.The multi-functional FK506 embedded,micropatterned poly（lactide-co-glycolic acid） films developed in this study have potential to be used in the construction of peripheral nerve repair devices.

关键词： nerve regeneration FK506 controlled release micropatterns topological cues PLGA

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Association of trainee participation with adenoma and polyp detection rates

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World Journal of Gastrointestinal Endoscopy 2017年第5期9卷 204-210页

作者： Emad Qayed Lauren shea Stephan Goebel Roberd m Bostick Department of medicine Division of Digestive diseasesEmory University School of Medicine Grady memorial Hospital Emory University Rollins School of Public Health Department of Epidemiology Emory University Winship Cancer Institute

To investigate whether adenoma and polyp detection rates (ADR and PDR, respectively) in screening colonoscopies performed in the presence of fellows differ from those performed by attending physicians alone. mETHODSWe performed a retrospective review of all patients who underwent a screening colonoscopy at Grady memorial Hospital between July 1, 2009 and June 30, 2015. Patients with a history of colon polyps or cancer and those with poor colon preparation or failed cecal intubation were excluded from the analysis. Associations of fellowship training level with the ADR and PDR relative to attendings alone were assessed using unconditional multivariable logistic regression. models were adjusted for sex, age, race, and colon preparation quality. RESULTSA total of 7503 colonoscopies met the inclusion criteria and were included in the analysis. The mean age of the study patients was 58.2 years; 63.1% were women and 88.2% were African American. The ADR was higher in the fellow participation group overall compared to that in the attending group: 34.5% vs 30.7% (P = 0.001), and for third year fellows it was 35.4% vs 30.7% (aOR = 1.23, 95%CI: 1.09-1.39). The higher ADR in the fellow participation group was evident for both the right and left side of the colon. For the PDR the corresponding figures were 44.5% vs 40.1% (P = 0.0003) and 45.7% vs 40.1% (aOR = 1.25, 95%CI: 1.12-1.41). The ADR and PDR increased with increasing fellow training level (P for trend ma and polyp detection.

关键词： Screening colonoscopy Adenoma detection rate Polyp detection rate Gastroenterology training Colorectal cancer

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Dynamic control of high-voltage actuator arrays by light-pattern projection on photoconductive switches

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microsystems & Nanoengineering 2023年第3期9卷 387-396页

作者： Vesna Bacheva Amir Firouzeh Edouard Leroy Aiste Balciunaite Diana Davila Israel Gabay Federico Paratore moran Bercovici Herbert shea Govind Kaigala Faculty of mechanical Engineering Technion-Israel Institute of Technology3200003 HaifaIsrael IBm Research Europe-Zurich Säumerstrasse 48803 RüschlikonSwitzerland Soft Transducers Laboratory(LmTS) Ecole Polytechnique Fédérale de Lausanne(EPFL)2000 NeuchâtelSwitzerland Present address:Laboratory of Soft materials and Interfaces ETH Zürich8093 ZürichSwitzerland Present address:School of Biomedical Engineering Vancouver Prostate CentreLife Sciences InstituteUniversity of British ColumbiaVancouverCanada

The ability to control high-voltage actuator arrays relies, to date, on expensive microelectronic processes or on individual wiring of each actuator to a single off-chip high-voltage switch. Here we present an alternative approach that uses on-chip photoconductive switches together with a light projection system to individually address high-voltage actuators. Each actuator is connected to one or more switches that are nominally OFF unless turned ON using direct light illumination. We selected hydrogenated amorphous silicon (a-Si:H) as our photoconductive material, and we provide a complete characterization of its light to dark conductance, breakdown field, and spectral response. The resulting switches are very robust, and we provide full details of their fabrication processes. We demonstrate that the switches can be integrated into different architectures to support both AC and DC-driven actuators and provide engineering guidelines for their functional design. To demonstrate the versatility of our approach, we demonstrate the use of the photoconductive switches in two distinctly different applications—control of µm-sized gate electrodes for patterning flow fields in a microfluidic chamber and control of cm-sized electrostatic actuators for creating mechanical deformations for haptic displays.

关键词： projection light sized

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Correlating the electronic structure of perovskite La_(1-x)SrxCoO_(3) with activity for the oxygen evolution reaction:The critical role of Co 3d hole state

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Journal of Energy Chemistry 2022年第2期31卷 637-645页

作者： Zechao Shen mei Qu Jueli Shi Freddy E.Oropeza Victor A.de la Peña O’shea Giulio Gorni C.m.Tian Jan P.Hofmann Jun Cheng Jun Li Kelvin H.L.Zhang State Key Laboratory of Physical Chemistry of Solid Surfaces College of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005FujianChina Photoactivated Processes Unit IMDEA Energy InstituteParque Tecnológico de MóstolesAvda.Ramón de la Sagra 328935 MóstolesMadridSpain CELLS-ALBA Synchrotron Carrer de la Llum 2-2608290 Cerdanyola del VallèsSpain Surface Science Laboratory Department of Materials and Earth SciencesTechnical University of Darmstadt Otto-Berndt-Strasse 364287 DarmstadtGermany

Perovskite LaCoO_(3) is being increasingly explored as an effective low-cost electrocatalyst for the oxygen evolution reaction(OER).Sr doping in LaCoO_(3)(La1-xSrxCoO_(3))has been found to substantially increase its catalytic *** this work,we report a detailed study on the evolution of the electronic structure of La1-xSrxCoO_(3) with 0≤x≤1 and its correlation with electrocatalytic activity for the OER.A combination of X-ray photoemission spectroscopy(XPS)and X-ray absorption spectroscopy(XAS)was used to unravel the electronic density of states(DOS)near the Fermi level(EF),which provide insights into the key electronic structure features for the enhanced OER catalytic *** analysis on the Co L-edge XAS suggest that LaCoO_(3) has a low spin state with t_(2g)^(6) e_(g)^(0) configuration at room *** implies that the high OER catalytic activity of LaCoO_(3) should not be rationalized by the occupancy of eg=1 *** Sr^(2+) for La^(3+) in LaCoO_(3) induces Co4+oxidation states and effectively dopes hole states into the top of valence band.A semiconductor-to-metal transition is observed for x>0.2,due to the holeinduced electronic DOS at the EF and increased hybridization between Co 3 d and O 2 *** an electronic modulation enhances the surface adsorption of the*OH intermediate and reduces the energy barrier for interfacial charge transfer,thus improving the OER catalytic activity in La_(1-x)Sr_(x)CoO_(3).In addition,we found that the La_(1-x)Sr_(x)CoO_(3) surface undergoes amorphization after certain period of OER measurement,leading to a partial deactivation of the *** Sr doping levels accelerated the amorphization process.

关键词： Perovskite oxide Oxygen evolution Cobalt Electronic structure

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Vertically aligned Ni/NiO nanocomposites with abundant oxygen deficient hetero-interfaces for enhanced overall water splitting

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Science China Chemistry 2022年第10期65卷 1885-1894页

作者： Hongxia Wang meiyan Cui Gaoliang Fu Jiaye Zhang Xingyu Ding Irene Azaceta matthew Bugnet Demie m.Kepaptsoglou Vlado K.Lazarov Victor Ade la Peña O’shea Freddy E.Oropeza Kelvin H.L.Zhang State Key Laboratory of Physical Chemistry of Solid Surfaces College of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China Henan Provincial Key Laboratory of Nanocomposites and Applications Institute of Nanostructured Functional MaterialsHuanghe Science and Technology CollegeZhengzhou 450006China Department of Physics University of YorkHeslingtonYorkYO105DDUK SuperSTEm Laboratory SciTech Daresbury CampusDaresbury WA44ADUK School of Chemical and Process Engineering Univeristy of LeedsLeeds LS29JTUK Univ Lyon CNRSINSA LyonUCBLMATEISUMR 551069621 VilleurbanneFrance Photoactivated Processes Unit IMDEA Energy InstituteParque Tecnológico de MóstolesAvda.Ramón de la Sagra 328935 MóstolesMadridSpain

The design of heterostructured transition metal-based electrocatalysts with controlled composition and interfaces is key to increasing the efficiency of the water electrolysis and the elucidation of reaction *** this work,we report the synthesis of well-controlled vertically aligned Ni/NiO nanocomposites consisting of Ni nanoclusters embedded in NiO,which result in highly efficient electrocatalysts for overall water *** show that such a high catalytic efficiency toward both the hydrogen evolution reaction(HER)and the oxygen evolution reaction(OER)originates from a synergetic effect at Ni/NiO interfaces that significantly reduces the energy barrier for water dissociation,and favours the formation of reactive H*intermediates on the Ni side of the interface,and OH_(ads) on the NiO side of the interface.A study of water chemisorption based on near-ambient pressure photoelectron spectroscopy indicates that the abundant hetero-interfaces in Ni/NiO nanocomposite promote the dissociation of water with a three-fold increase in the surface concentration of OH_(ads) compared with pure *** functional theory calculations indicate that Ni/NiO interface leads to the reduction of the water dissociation energy barrier due to a high concentration of oxygen vacancies at NiO side of the interface,whereas the formation of highly active metallic Ni sites with an optimal value of Gibbs free energy of H*(ΔG_(H*)=−0.16 eV)owes to a favourable adjustment of the electron energetics at the interface,thus accelerating the overall electrochemical water splitting.

关键词： water splitting hydrogen evolution reaction electronic structure heterostructure vertically aligned nanocomposites

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活细胞微囊化——长效释放体系

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药学进展 1991年第2期15卷 90-92页

作者： A m Sun G.m.O'shea 朱央央

引言固定化酶和其它大分子已被制成许多在工业和医学上使用的长效释药体系。但是,这些体系受下列因素限制:(A)包于释药体系的物质数量受限;(B)体系的非控释性;(C)需用外科手术取出不降解骨架;(D)骨架的生物相容性差。理论上讲,采用细胞... 详细信息

引言固定化酶和其它大分子已被制成许多在工业和医学上使用的长效释药体系。但是,这些体系受下列因素限制:(A)包于释药体系的物质数量受限;(B)体系的非控释性;(C)需用外科手术取出不降解骨架;(D)骨架的生物相容性差。理论上讲,采用细胞微囊化作为激素、酶和其它大分子的释药体系有一定优点,因在生物相容膜内的细胞.由于免疫隔离使副反应减少,同时使细胞分泌物的生理性释放延长。本文叙述有关藻酸盐—聚赖氨酸—藻酸盐膜包囊的胰岛、肝细胞的体内外长效性研究。材料和方法动物杂交Wistar大鼠,雄性。

关键词：活细胞微囊化长效释放体系

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Herpetological Diversity of Timor-Leste: Updates and a Review of Species Distributions

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Asian Herpetological Research 2015年第2期6卷 73-131页

作者： mark O'shea Caitlin SANCHEZ Andrew KATHRINER Sven mECKE Venancio LOPES CARVALHO Agivedo VARELA RIBEIRO Zito AFRANIO SOARES Luis LEmOS DE ARAUJO Hinrich KAISER Faculty of Science and Engineering University of Wolverhampton Wulfruna Street Wolverhampton WV1 1LY United Kingdom and West midland Safari Park Bewdley Worcestershire DY12 LF United Kingdom Department of Biology Victor Valley College Department of Biology Villanova University 800 East Lancaster Avenue Villanova Pennsylvania 19085 USA Department of Herpetology Bronx Zoo 2300 Southern Boulevard Bronx New York 10460 USA Department of Animal Evolution and Systematics Faculty of Biology Philipps Universit?t Marburg Universidade National Timor-Lorosa’e Faculdade de Ciencias da Educa?ao Departamentu da Biologia Avenida Cidade de Lisboa Liceu Dr. Francisco Machado Dili Timor-Leste Department of Vertebrate Zoology National Museum of Natural History Smithsonian Institution

We report the results of five herpetological surveys during 2011-2013 that included visits to all districts of Timor-Leste （Aileu, Ainaro, Baucau, Bobonaro, Dili, Covalima, Ermera, Laut6m, Liquiga, manatuto, manufahi, Viqueque） except the Oecusse exclave. Our fieldwork culminated in the discovery of one putative new frog species （genus Kaloula）, at least five putative new lizard species （genera Cyrtodactylus, Cryptoblepharus, and Sphenomorphus）, and two putative new snake species （genera Stegonotus and Indotyphlops）. In addition, we present new distribution records of amphibians and reptiles for 11 of the country＇s 12 contiguous districts, along with additional natural history data. Results from our surveys increase the number of amphibian and reptiles known to occur in Timor-Leste from 22 species before our surveys began to over 60, including over 20 as yet undescribed species.

关键词： Timor-Leste Kaloula Cyrtodactylus Eremiascincus Stegonotus

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