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ca^(2+) binding to the c_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

Protein & cell 2024年第4期15卷 305-312页

作者： Han chen Mehar Monga Qinghua Fang Loujin Slitin Jakob Neef Shashank S.chepurwar Regina célia Mingroni Netto Karina Lezirovitz Alfredo Tabith,Jr. Fritz Benseler Nils Brose Kathrin Kusch carolin Wichmann Nicola Strenzke Barbara Vona julia Preobraschenski Tobias Moser Institute for Auditory Neuroscience and InnerEarLab University Medical Center Göttingen37075 GöttingenGermany collaborative Research center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and Synaptic Nanophysiology Group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Göttingen Graduate center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics Group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of Synapses Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory Systems Physiology Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de Genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil Laboratório de Otorrinolaringologia/LIM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DERDIc Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging cluster of Excellence(MBExc) University of Göttingen37075 GöttingenGermany Functional Auditory Genomics Group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany Hearing Genomics Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Institute of Human Genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(IHcs)employ a unique molecular machinery(see extended background in Supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and Starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-c_(2)-domain protein(Fig.1Ai)specific to hair cells(Roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of major disease relevance(Pangršičet al.,2012),also see Supplementary *** is distributed broadly within IHcs(Fig.2Ai-Aiii;Pangrsic et al.,2010;Roux et al.,2006).

关键词： auditory hair

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Barosinusitis due to routine weather changes:A cross-sectional analysis of public websites

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 18-23页

作者： James c.campbell julia E.canick Philip G.chen Ralph Abi Hachem David W.Jang Department of Head and Neck Surgery&communication Sciences Duke University School of MedicineDurhamNorth CarolinaUSA Duke University School of Medicine DurhamNorth CarolinaUSA Department of Otolaryngology-Head and Neck Surgery University of Texas Health Science Center San AntonioSan AntonioTexasUSA

Background:Sinusitis is a common diagnosis that can be erroneously associated with routine weather‐related barometric pressure *** actuality,these pressure changes likely exacerbate migraine headaches,which can cause facial pain and pressure rather than true sinus ***:The present study sought to characterize the representation of both sinusitis and migraine in association with barometric pressure changes across websites on the ***:An Internet search for relevant terms was conducted,and content of the resulting pages was assessed for associations between weather‐related pressure changes and either sinusitis or *** in reported results across different subtypes of Internet sources were *** primary outcomes measured were(1)whether a given media source associated barometric weather changes with sinusitis,(2)whether that source associated barometric weather changes with migraine,and(3)treatment options offered by that ***:Of the 116 included webpages,36(31.03%)associated sinusitis and routine barometric pressure *** these,10(27.77%)were otolaryngology practice ***‐seven webpages(57.76%)associated migraine and routine barometric pressure *** these,nonotolaryngology webpages were more likely to report this ***:Otolaryngology practice sites were observed to be the most frequent professional medical resource reporting the unsubstantiated claim that routine barometric pressure changes are associated with *** sources were more likely to link weather‐related pressure changes to *** results suggest that opportunities exist for otolaryngology practice sites to educate patients about nonrhinogenic headache etiologies.

关键词： acute rhinosinusitis balloon sinus dilation headache migraine sinusitis

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Otolaryngology residency program factors associated with female resident representation

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 7-11页

作者： julia E.canick James c.campbell charles R.Woodard Lars J.Grimm Alissa M.collins Duke University School of Medicine DurhamNorth CarolinaUSA Department of Head and Neck Surgery&communication Sciences Duke University School of MedicineDurhamNorth CarolinaUSA Department of Radiology Duke University School of MedicineDurhamNorth CarolinaUSA

Objective:Female representation in the field of otolaryngology is *** is the first point at which medical school graduates specialize in a chosen field and thus represents an opportunity to recruit and train more female *** study sought to identify program factors associated with greater female representation among resident ***:Departmental websites of all 124 otolaryngology residency programs in the United States and Puerto Rico were examined for a list of *** programs with a resident roster available,the genders of residents,faculty,program directors,and chairpersons were *** and city population for each program was also recorded,as was female resident *** were compared using Pearson chi‐squared univariate ***:1,632 residents and 2,605 faculty were included in the analysis of 109 *** median female resident representation was 40%.Programs with larger faculty sizes,more female faculty,and urban location were associated with an above‐median female resident *** with a larger residency cohort approached significance regarding above‐median female resident *** female faculty representation,program director gender,chairperson gender,and US region were not associated with variation in female resident ***:Greater female otolaryngology residency representation was associated with programs having an urban location and greater numbers of female and total *** was also likely that a larger resident cohort size may affect female resident *** proportions of female faculty,program director,and chairperson gender,as well as the US region,were not associated with variation in female resident gender representation.

关键词： gender program director recruitment residency training

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Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes

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World Journal of Diabetes 2024年第8期15卷 1717-1725页

作者： Jorge M Molina Patricia G Medina Rita A Gomez julia R Herrera Nancy L Martínez Brenda Hernández Yesenia García Department of Endocrinology Children’s Hospital Federico GomezMexico 06720Mexico National Medical center"Siglo XXI" UMAE Hosp EspecialidadesUnidad Invest Med Epidemiol ClinMexican Social Security InstituteMexico 06720Mexico Research Division UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIMexican Institute of Social SecurityMexico 06720Mexico Epidemiology Research Unit in Endocrinology and Nutrition Federico Gómez Children’s HospitalMexico 06720Mexico Department of Endocrinology Comprehensive Health Unit for Trans PersonsMexico 11340Mexico

BAcKGROUND Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus(T2DM),that is,patients who have insulin resistance,obesity,and other cardiovascular risk factors,suggesting that the presence of glutamic acid decarboxylase(anti-GAD65),islet antigen 2(anti-IA2),and zinc transporter 8(anti-Zn8T)antibodies could have deleterious effects on beta cell function,causing failure and earlier requirement for insulin *** To evaluate anti-GAD65,anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of *** This was a case–control study in patients with clinically diagnosed with T2DM(68 cases and 64 controls with and without early insulin dependence respectively),male and female,aged 12–18 ***,blood pressure,glucose,insulin,c-peptide,glycated hemoglobin A1c,and lipid profiles were *** was used to measure anti-GAD65,anti-IA2,and anti-Zn8T *** statistics,Pearson'sχ2 test,Student's t test,and logistic regression was performed.Pconsidered statistically *** There were 132 patients(53.8%female),with a mean age was 15.9±1.3 years,and there was a disease evolution time of 4.49±0.88 *** presence of anti-GAD65,anti-IA2,and anti-Zn8T positivity was found in 29.5%,18.2%,and 15.9%,*** the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity:anti-GAD65 odds ratio(OR):2.42(1.112–5.303,P=0.026);anti-IA2:OR:1.55(0.859–2.818,P=0.105);and anti-Zn8T:OR:7.32(2.039–26.279,P=0.002).cONcLUSION Anti-GAD65 positivity was high in our ***-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype,leading to an increased risk of early insulin dependence.

关键词： Diabetes Obesity Adolescents Autoimmunity Beta cell Insulin requirements

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Modeling and Simulation of an Organic Photovoltaic cell: ITO/MoO3/cARAPA/PcBM/Alq3/Al with ScAPS

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Modeling and Numerical Simulation of Material Science 2024年第3期14卷 79-96页

作者： Donafologo Soro Adama Sylla Aboudramane Gbané Bamba Abdoulaye Franck julia Mari Guaita Amal Bouich Siaka Toure Bernabé Marí Dpartement des Sciences et Technologie Ecole Normale Suprieure (ENS) dAbidjan Abidjan Cte dIvoire LASMES Laboratory (Laboratory of Material Sciences Environment and Solar Energy) Universit FHB DAbidjan-Cocody Abidjan Cte dIvoire Unit de Formation et de Recherche Sciences Technologiques Universit de Man Man Cte dIvoire Departament de Fsica Aplicada-IDF Universitat Politcnica de Vlencia Vlencia Spain

Renewable energies are of major interest due to their inexhaustible and clean nature, with minimal impact on the environment. Numerous technological pathways exist in this field, each distinguished by the materials used and their implementation principles. However, the cost-efficiency ratio remains a significant challenge for researchers. currently, organic materials are gaining popularity due to their relatively low cost. However, their performance, particularly in terms of conversion efficiency, still requires improvements. This study focuses on optimizing the organic photovoltaic cell ITO/MoO3/cARAPA/PcBM/Alq3/Al using ScAPS. Several parameters were considered, such as layer thickness, recombination center density, and doping, to improve the cell’s performance. The optimal parameters obtained include an efficiency of 3%, a fill factor of 81.67%, an open-circuit voltage of 1610 mV, and a short-circuit current of 2.28 mA/cm2. The study also revealed that doping the phenyl-c61-butyric acid methyl ester (PcBM) layer has a significant impact on efficiency and short-circuit current, improving these parameters up to a certain point before causing degradation due to increased recombination. Furthermore, high doping of the tri (8-hydroxyquinoline) aluminum (Alq3) layer improves performance up to a critical threshold, after which degradation is also observed. In contrast, doping the molybdenum trioxide (MoO3) layer does not have a notable impact on cell performance. Regarding the thickness of the active carapaprocera (cARAPA) and PcBM layers, non-optimal values lead to a decrease in performance. Similarly, an optimal thickness of the Alq3 layer significantly improves efficiency. These results highlight the importance of parameter optimization to maximize the efficiency of organic solar cells.

关键词： Renewable Energie Solar cells Simulation Organic Materials Performance

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Polycystic Ovarian Syndrome (PcOS): Exploring Its Impact on Obstetrical Outcomes

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Open Journal of Obstetrics and Gynecology 2024年第8期14卷 1111-1123页

作者： Ranjitha Vasa Gayatri Venkataraman Kelly Gorman Rythika Francis Elise Zwicklbauer julia Fisher Polina Safovich Mudar Dalloul Ozgul Muneyyirci-Delale Department of Obstetrics and Gynecology SUNY Downstate Health Science University Brooklyn United States of America Department of Obstetrics and Gynecology Kings County Hospital Center NYC Health and Hospitals Brooklyn United States of America

Polycystic ovarian syndrome (PcOS) disrupts ovulation leading to both infertility and miscarriage;yet, its impact on obstetrical outcomes remains largely uncertain due to conflicting findings. We analyzed data from the cDc Pregnancy Risk Assessment of Monitoring System, specifically Standard core and Phase 8 responses, with 9549 respondents across the United States through SPSS 28 software in this cross-sectional study. Two variables assessed PcOS status in respondents: history of PcOS and PcOS during pregnancy. With a history of PcOS, there were significantly increased odds of diabetic (OR 1.665, p cy, neonatal mortality (OR 1.550, p cesarean section (c/S) (OR 1.489, p cOS diagnosed during pregnancy, there were significantly greater odds of diabetes (OR 3.278, p cy, and significantly decreased risk for small for gestational age (2 standard deviations) (OR 0.337, p = 0.024). PcOS is a significant risk factor that contributes to maternal morbidity. Our results support the hypothesis that PcOS’ impact extends well into a woman’s obstetrical journey, with varying degrees of associated adverse maternal and fetal risks. Preliminary pathophysiologic explanations associated with PcOS gestational diabetes include pre-existing insulin resistance. Meanwhile, altered placentation and endovascular changes associated with PcOS secondary to a baseline deranged metabolic environment predispose patients to developing hypertensive disorders, PPROM, and preterm delivery. Associations between neonatal mortality and c/S can be attributed to elevated maternal body mass index. The pathophysiologic link between PcOS and the above obstetrical outcomes still remains unknown, necessitating further investigation;however, this study identifies the outcomes that

关键词： PcOS Polycystic Ovarian Syndrome Obstetrics Reproduction Pregnancy

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Understanding chemical Reactivity in Extended Systems：Exploring Models of chemical Softness in carbon Nanotubes

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物理化学学报 2018年第6期34卷 631-638页

作者： cáRDENAS carlos MUNOZ Macarena cONTRERAS julia AYERS Paul W. GóMEZ Tatiana FUENTEALBA Patricio Departamento de Flsica Facultad de Ciencias Universidad de Chile Casilla 653 Santiago Chile centro para el Desarrollo de la Nanociencias y Nanotecnologia CEDENNA Avenida Ecuador 3493 Santiago Chile Nucleo de Matematicas Fisica y Estad

chemical reactivity towards electron transfer is captured by the Fukui ***,this is not well defined when the system or its ions have degenerate or pseudo-degenerate ground *** such a case,the first-order chemical response is not independent of the perturbation and the correct response has to be computed using the mathematical formalism of perturbation theory for degenerate ***-degeneracy is ubiquitous in nanostructures with high symmetry and totally extended *** the size of these systems,using degenerate-state perturbation theory is impractical because it requires the calculation of many excited *** we present an alternative to compute the chemical response of extended systems using models of local softness in terms of the local density of *** local softness is approximately equal to the density of states at the Fermi ***,such approximation leaves out the contribution of inner *** order to include and weight the contribution of the states around the Fermi level,a model inspired by the long-range behavior of the local softness is *** wall capped carbon nanotubes(SWccNT) illustrate the limitation of the frontier orbital theory in extended ***,we have used a c360 SWccNT to test the proposed model and how it compares with available models based on the local density of ***,a simple Hü ckel approximation captures the main features of chemical response of these *** results suggest that density-of-states models of the softness along simple tight binding Hamiltonians could be used to explore the chemical reactivity of more complex system,such a surfaces and nanoparticles.

关键词： Local softness Fukui function Reactivity carbon nanotubes Density of states

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Behavioural and energetic consequences of competition among three overwintering swan(cygnus spp.)species

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Avian Research 2021年第4期12卷 707-721页

作者： Kevin A.Wood julia L.Newth Geoff M.Hilton Eileen c.Rees Wildfowl&Wetlands Trust SlimbridgeGloucestershire GL27BTUnited Kingdom centre for Ecology and conservation/Environment and Sustainabil-ity Institute College of Life and Environmental SciencesUniversity of ExeterExeter TR109EZUnited Kingdom Department of Zoology University of CambridgeDowning StreetCambridge CB23EJUnited Kingdom

Background:Winter numbers of the northwest European population of Bewick's Swans(cygnus columbianus bewickii)declined recently by c.40%.During the same period,numbers of two sympatric and ecologically-similar congeners,the Mute Swan(cygnus olor)and Whooper Swan(cygnus cygnus)showed increases or *** has been suggested that these opposing population trends could have a causal relationship,as Mute and Whooper Swans are larger and competitively dominant to Bewick's Swans in foraging *** so,effects of competition of Mute and Whooper Swans on Bewick's Swans should be detectable as measurable impacts on behaviour and ***:Here,we studied the diurnal behaviour and energetics of 1083 focal adults and first-winter juveniles("cygnets")of the three swan species on their winter grounds in eastern *** analysed video recordings to derive time-activity budgets and these,together with estimates of energy gain and expenditure,were analysed to determine whether individual Bewick's Swans altered the time spent on key behaviours when sharing feeding habitat with other swan species,and any consequences for their energy expenditure and net energy ***:All three swan species spent a small proportion of their total time(0.011)on aggressive interactions,and these were predominantly intraspecific(≥0.714).Mixed-effects models indicated that sharing feeding habitat with higher densities of Mute and Whooper Swans increased the likelihood of engaging in aggression for cygnet Bewick's Swans,but not for *** levels of interspecific competition decreased the time spent by Bewick's Swan cygnets on foraging,whilst adults showed the opposite *** among low densities of conspecifics(c.200 individuals/km^(2)),individual Bewick's Swans spent more time on vigilance in the presence of higher densities of Mute and Whooper Swans,whilst individuals within higher density Bewick's Swan flocks showed the opposite ***,we found no evide

关键词： Avian behaviour Energy expenditure Ethology Interference competition Interspecific interactions Time activity budgets Video observations

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Early Holocene climate signals from stable isotope composition of ice wedges in the chara Basin,northern Transbaikalia,Russia

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Geoscience Frontiers 2018年第2期9卷 471-483页

作者： Yurij K.Vasil’chuk Alla c.Vasil’chuk julia V.Stanilovskaya Geography and Geology Departments Lomonosov Moscow State UniversityMoscowRussia Sergeev Environmental Geoscience Institute of the Russian Academy of Sciences Russia

Stable isotope composition of syngenetic and epigenetic ice wedges, radiocarbon age, and pollen spectra of the surrounding deposits were studied during long term investigations at the "Belyi Klyuch" site on the first(6-8 m height) terrace of the chara River(720 m.a.s.l.) in northern Transbaikalia to assess climatic conditions during ice-wedge formation. It was revealed that Holocene ice wedges had been formed from 10 to 7.5 ka 14 c BP. The isotope composition(δ^(18)O, δ~2 H) of relict ice wedges is the lightest and amounts-23‰ and-185‰, correspondingly. The isotopic compositions of ice lenses from sandy loam above ice wedges are-15.7‰, and-133‰; of small ice wedge in peat and sand are-15.3‰ and-117.9‰, *** of the ice wedge isotope composition has yielded that mean winter temperatures during cold stages of Holocene optimum were lower than today, during warm stages they were close to modern ones. During the coldest stages of Holocene optimum the total annual freezing index varied from-5100 to-5700 ℃ degree days, i.e. 300-600 ℃ degree days colder than during extremely severe modern winters. The total annual thawing index varied from 1300 to 1800 ℃ degree days, which was slightly higher than modern ones.

关键词： Holocene Ice wedge Stable isotopes Southern permafrost areas Northern Transbaikalia

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Moth Flame Optimization Based FcNN for Prediction of Bugs in Software

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Intelligent Automation & Soft computing 2023年第5期36卷 1241-1256页

作者： c.Anjali julia Punitha Malar Dhas J.Amar Pratap Singh Department of cSE Noorul Islam Center for Higher Studies629180Tamil NaduIndia

The software engineering technique makes it possible to create high-quality *** of the most signiﬁcant qualities of good software is that it is devoid of *** of the most time-consuming and costly software proce-dures isﬁnding andﬁxing *** it is impossible to eradicate all bugs,it is feasible to reduce the number of bugs and their negative *** broaden the scope of bug prediction techniques and increase software quality,numerous causes of software problems must be identiﬁed,and successful bug prediction models must be *** study employs a hybrid of Faster convolution Neural Network and the Moth Flame Optimization(MFO)algorithm to forecast the number of bugs in software based on the program data itself,such as the line quantity in codes,methods characteristics,and other essential software ***,the MFO method is used to train the neural network to identify optimal *** proposed MFO-FcNN technique is compared with existing methods such as AdaBoost(AB),Random Forest(RF),K-Nearest Neighbour(KNN),K-Means clustering(KMc),Support Vector Machine(SVM)and Bagging clas-siﬁer(Bc)are examples of machine learning(ML)*** assessment method revealed that machine learning techniques may be employed successfully and through a high level of *** obtained data revealed that the proposed strategy outperforms the traditional approach.

关键词： Faster convolution neural network Moth Flame Optimization(MFO) Support Vector Machine(SVM) AdaBoost(AB) software bug prediction

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