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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 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

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Investigating low dispersion isotope dissolution Lu-Hf garnet dates via in situ Lu-Hf geochronology,Kanchenjunga Himal

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Geoscience Frontiers 2024年第3期15卷 137-145页

作者： Kyle p.Larson John M.Cottle Mark Button Brendan Dyck Iva Lihter Sudip Shrestha Department of Earth Environmental and Geographic SciencesUniversity of British ColumbiaOkanaganKelownaCanada Department of Earth Science University of CaliforniaSanta BarbaraUSA Fipke Laboratory for Trace Element Research University of British ColumbiaOkanaganKelownaCanada

Re-examination of three specimens from the Kanchenjunga Himal of Nepal via in situ Lu-Hf garnet geochronology yields evidence of multiple garnet growth *** analyses from grain cores in two specimens define paleozoic regressions whereas analyses from grain rims in the same specimens define low-precision regressions consistent with the timing of Himalayan *** dates contrast with previously published low dispersion,ca.290 Ma isotope dissolution(ID)Lu-Hf garnet dates for the same *** of Lu and spot age distribution in representative grains from the specimens examined yields calculated dates that approximate the permian-age regressions through the original ID *** findings demonstrate that it is possible to generate low dispersion ID Lu-Hf data from multigenerational garnet with significantly different-age growth events when approximately equal proportions of the different age reservoirs are included in multi-component aliquots.

关键词： Lu-Hf geochronology In situ Lu-Hf geochronology Kanchenjunga Himal

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predictive Modeling of Sedentary Behavior patterns in Adults Using Stacked LSTM

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Journal of Harbin Institute of Technology(New Series) 2024年第4期31卷 74-84页

作者： p Sanju Department of Computer Science and Engineering University College of Engineering TindivanamTamil Nadu 604001India

A new health concern in recent periods has seen the evolution of uncertain sedentary *** sedentary for extended durations is regarded as a notable hazard across various adult age brackets,especially the excessive dependence on automobiles for *** the active period,monitoring seating habits has been made easier by ***,there exists a disagreement among professionals regarding the most suitable quantifiable criteria for encompassing the comprehensive data on sedentary behavior throughout the *** to variations in measurement methodologies,data analysis approaches,and the lack of essential outcome indicators such as the total sedentary duration,the assessment of sedentary patterns in numerous research investigations was considered *** research suggested fleeting granularity distinguish occurrences of regular human *** units(essential cells) acquire multivariate transitory *** Behavior patterns(FBps) can be identified with a estimation of timeframe using our proposed scalable algorithms that employ collected widespread multivariate data(fleeting granularity).The research outcome,supported by rigorous analyses on two validated datasets,mark a significant *** the final stages of the study,a stacked Long Short-Term Memory(LSTM) model was utilized to replicate and forecast repetitive sedentary behavior patterns,leveraging data from the preceding six-hour window blocks of sedentary *** model effectively replicated state traits,previous action sequences,and duration,attaining an impressive 99% accuracy level as assessed through RMSE,MSE,MApE,and r-correlation metrics.

关键词： health care sedentary behavior LSTM

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Effect of stress-dependent microannulus aperture on well leakage

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第6期16卷 1967-1976页

作者： Meng Meng Luke p.Frash J.William Carey Mohamed Mehana Wenfeng Li Bailian Chen Earth and Environmental Sciences Los Alamos National LaboratoryLos AlamosNMUSA

Debonding at the cement-casing interface is recognized as a principal failure mechanism leading to CO_(2) leakage in *** detachment gives rise to a microannulus,which notably possesses greater permeability than undamaged cement,undermining its sealing ***,the permeability of the microannulus is regarded as a uniform value throughout the ***,fundamentally,a microannulus is one type of fracture,and its gap or aperture size is affected by the effective *** this work,we developed a unique experimental *** equipment facilitates the curing of cement inside a steel casing,the formation of a microannulus between the casing and the cement,and the investigation of the fluid flow dynamics along the microannulus under laboratory-replicated in situ *** microannulus was formed by injecting fluid from one end of the setup,and receiving similar amount of fluid on the other end signified the development of the leakage ***,strain gauges affixed to the casing’s external surface yielded key information on the microannulus’s opening and *** observed a noticeable decline in microannulus hydraulic aperture(or permeability)in relation to effective stress and an exponential equation fits their *** findings also indicate a distinct behavior when comparing liquid CO_(2) with ***,it is easier for liquid CO_(2) to create the ***,the hydraulic aperture range for this microannulus(0.7-6 mm)is considerably smaller than that created by water flow(2-17 mm).Finally,we integrated the stressdependent microannulus aperture size into the combined analysis of well mechanical integrity and well *** outcomes consistently demonstrated that when factoring in the stress-dependent aperture sizes,the leakage rates are 3e5 times compared to a fixed aperture *** traditional assumption of a constant aperture significantly underestimates fluid leakage risks.

关键词： Microannulus Leakage assessment Aperture size Triaxial experiment Carbon sequestration

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Efficiency and effectiveness of systems for the treatment of domestic wastewater based on subsurface flow constructed wetlands in Jarabacoa, Dominican Republic

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Water Science and Engineering 2024年第2期17卷 118-128页

作者： Yvelisse pérez Enmanuel Vargas Daniel Garcia-Cortes William Hernandez Humberto Checo Ulises Jauregui-Haza Area de Ciencias Basicas y Ambientales Instituto Tecnologico de Santo Domingo(INTEC)Avenida de Los Proceres 49Los Jardines del NorteSanto Domingo 10602Dominican Republic Ministry of Environment and Natural Resources Calle Cayetano Germosen esq.Ave.LuperonEl PedregalSanto Domingo 11107Dominican Republic plan Yaque Calle Estela Geraldino 14 AltosJarabacoa 41000Dominican Republic Institute of Technologies and Applied Sciences University of HavanaHavana 10400Cuba

Constructed wetlands(CwW)are well known nature-based systems for water *** study evaluated the efficiency and effectiveness of seven domestic wastewater treatment systems based on horizontal flow CWs in Jarabacoa,the Dominican *** results showed that the CWs were efficient in reducing the degree of contamination of wastewater to levels below the Dominican wastewater discharge standards for parameters such as the 5-day biochemical oxygen demand(BOD5)and chemical oxygen demand,but not for the removal of phosphorus and fecal *** addition,a horizontal flow subsurface wetland in the peri-urban area El Dorado was evaluated in terms of the performance of wastewater treatment in tropical climatic *** concentrations of heavy metals,such as zinc,copper,chromium,and iron,were found to decrease in the effluent of the wetland,and the concentrations for nickel and manganese tended to *** levels of heavy metals in the effluent were lower than the limit values of the Dominican wastewater discharge *** construction cost of these facilities was around 200 USD per population equivalent,similar to the cost in other countries in the same *** study suggested some solutions to the improved performance of CWs:selection of a microbial flora that guarantees the reduction of nitrates and nitrites to molecular nitrogen,use of endemic plants that bioaccumulate heavy metals,combination of constructed wetlands with filtration on activated carbon,and inclusion of water purification processes that allow to evaluate the reuse of treated water.

关键词： Domestic wastewater Constructed wetland BOD COD pathogens Heavy metals

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Seasonal changes in Hermit Thrush (Catharus guttatus) song syntax

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Avian Research 2024年第2期15卷 172-179页

作者： Sean p.Roach Luke C.McLean Jeff W.MacLeod Leslie S.phillmore psychology Department University of New Brunswick Saint John100 Tucker Park RoadSaint JohnNBCanada Department of psychology and Neuroscience Dalhousie University1355 Oxford StHalifaxNSB3H 4J1Canada

In many songbird species,birdsong features phonological syntax,meaning that the units within their vocal se-quences are ordered in a non-random way that adheres to a *** such syntactical patterns have been richly described in many species,comparatively little is known about how those patterns contribute to song achieving its important *** each of song’s main functions,territorial defense and mate attraction,evidence of a role for syntax is *** species for which syntax has been thoroughly described is the Hermit Thrush(Catharus guttatus),which presents song types from their repertoires in a semi-predictable order and,in doing so,rapidly cycle up and down the frequency *** objective of the present study was to explore the importance of song syntax in the Hermit Thrush through a within-subject examination of how measures of syntax,such as the predictability of song type order within song sequences,shift over the breeding *** hypothesized that,if such syntactical characteristics are important to breeding behaviour,they would be most prominent at the start of the breeding season when activity associated with territory establishment and mate attraction is most *** revealed that,as predicted,the rigidness of song type ordering within se-quences was highest at the start of the season and declined *** song type sequences were most predictable at the vitally important early part of the breeding season fit our hypothesis that this aspect of song syntax is important to song’s functions related to territory establishment and/or mate *** work will clarify whether that role relates to one of song’s two main functions or serves song transmission in some broader way.

关键词： Birdsong Hermit Thrush Seasonal change Stereotypy Syntax

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Diagnostic challenges and individualized treatment of cervical adenocarcinoma metastases to the breast:A case report

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World Journal of Clinical Cases 2024年第2期12卷 412-417页

作者： Allison Akers Susan Read John Feldman Casey Gooden Diana p English Department of Obstetrics and Gynecology University of South FloridaTampaFL 33606United States Department of Gynecologic Oncology Sky Ridge Medical CenterLone TreeCO 80124United States Department of Radiology University of South FloridaTampaFL 33606United States Department of pathology University of South FloridaTampaFL 33606United States

BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in *** metastases are associated with poor *** following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized *** SUMMARY A 44-year-old G7p5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node *** biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(pET/CT)did not show evidence of metastatic *** received concurrent cisplatin with external beam radiation *** up pET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic *** was lost to follow up for six *** was re-imaged on re-presentation and found to have widely metastatic disease including breast *** biopsy confirmed programmed death-ligand 1 positive metastatic cervical *** patient received six cycles of carboplatin and paclitaxel with *** imaging demonstrated *** continued on pembrolizumab with disease *** Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis *** history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the ***,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.

关键词： Cervical adenocarcinoma Breast metastases Immunotherapy pembrolizumab Carboplatin paclitaxel Case report

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Challenging the term symbiosis in plant-microbe associations to create an understanding across sciences

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Journal of Integrative plant Biology 2024年第1期66卷 7-11页

作者： Anna Neubauer Daniela Aros‐Mualin Vicente Mariscal péter Szövényi Department of Systematic and Evolutionary Botany University of ZurichZurich 8008Switzerland Zurich‐Basel plant Science Center Zurich 8092Switzerland Instituto de Bioquímica Vegetal y Fotosíntesis CSIC y Universidad de SevillaSevilla 41092Spain

THE IMpORTANCE OF WELL DEFINED TERMINOLOGY,Effective communication across fields and disciplines relies on well defined *** use of accurate definitions has been advocated by scientists across various disciplines(pySek... 详细信息

关键词： terminology definition fields

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Ion-conducting Membranes Based on Bacterial Cellulose Nanofibers Modified by poly(sodium acrylate-co-2-acrylamido-2-methylpropanesulfonic acid)

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Chinese Journal of polymer Science 2024年第3期42卷 333-343,I0007页

作者： Elizaveta V.Batishcheva Nikolay N.Smirnov Natalya V.Bobrova Maria p.Sokolova Michael A.Smirnov Institute of Macromolecular Compounds Russian Academy of SciencesBolshoy pr.31Saint Petersburg 199004Russia

Green method for preparation of ion-conducting membranes(ICM) based on bacterial cellulose nanofibers(CNF) modified by a copolymer of sodium acrylate and 2-acrylamido-2-methylpropanesulfonic acid was elaborated. FTIR and NMR data confirmed grafting of polyacrylate onto cellulose surface. Formation of porous structure of the ICM was controlled by SEM and AFM. The maximal ionic conductivity of the membranes reaches 1.5 and 3.1 mS·cm^(-1)(60 ℃ and 98% relative humidity) when they are saturated with water or H_2SO_4(1 mol·L^(-1)) electrolyte,respectively. prepared ICM was tested as a separator in a symmetrical supercapacitor with electrodes based on polyaniline hydrogel. The assembled cell demonstrate ability to operate at high current density up to 100 A·g^(-1) maintaining specific capacitance 165 F·g^(-1). Maximal specific capacitance of 289 F·g^(-1) was achieved at current density 1 A·g^(-1). Retaining of 90% of initial capacitance after 10000 of charge-discharge cycles proves high electrochemical stability of prepared ICM.

关键词： Bacterial cellulose Ion conductivity porous membrane Supercapacitor

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Comparative Study of the Effects of Nano ZnO and CuO on the Biodegradation,Biocompatibility,and Antibacterial properties of Micro-arc Oxidation Coating of Magnesium Alloy

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Acta Metallurgica Sinica(English Letters) 2024年第2期37卷 242-254页

作者： Ying Shen Xianfeng Shan Iniobong p.Etim Muhammad Ali Siddiqui Yang Yang Zewen Shi Xuping Su Junxiu Chen Key Laboratory of Materials Surface Science and Technology of Jiangsu province Changzhou UniversityChangzhou213164China Department of Stomatology The Affiliated Xinhua Hospital of Dalian UniversityDalian116000China Department of physics University of CalabarCalabar540242Nigeria Metallurgical Engineering Department NED University of Engineering and TechnologyUniversity RoadKarachi75270Pakistan Ningbo No.2 Hospital Ningbo315010China

This research systematically examined the degradation,antibacterial effects,and biocompatibility of micro-arc oxidation(MAO)coatings with nano CuO and ZnO on extruded Mg *** copper(Cu)and Zinc(Zn)possess antibacterial *** findings demonstrated that adding ZnO will appreciably reduce the degradation rate of MAO-coating alloy due to the self-sealing micro ***+MAO coating exhibited excellent antibacterial performance,with an antibacterial rate of over 90%within 6 h co-cultured with Staphylococcus ***,the antibacterial rate of ZnO+MAO coating reached 90%after 12 h *** test using MG63 cell indicated that the incorporation of CuO and ZnO did not notably affect the cell viability rate of the ***,after 14 days of culture,the CuO+MAO and ZnO+MAO coated samples exhibited higher alkaline phosphatase(ALp)activity than the MAO-coated and uncoated samples,suggesting favorable osteogenic properties.

关键词： Copper oxide Zinc oxide Micro-arc oxidation(MAO)coating Corrosion behavior Antibacterial characteristics

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