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Navigating the dynamic landscape of alpha-synuclein morphology: a review of the physiologically relevant tetrameric conformation

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Neural Regeneration Research 2020年第3期15卷 407-415页

作者： heather R.lucas Ricardo d.Fernández department of Chemistry Virginia Commonwealth University

N-acetylatedα-synuclein(αSyn)has long been established as an intrinsically disordered protein associated with a dysfunctional role in Parkinson’s *** recent years,a physiologically relevant,higher order conformation has been identified as a helical tetramer that is tailored by buried hydrophobic interactions and is distinctively aggregation *** canonical mechanism by which the tetramer assembles remains *** novel biochemical approaches,computational methods,pioneering purification platforms,and powerful imaging techniques continue to develop,puzzling information that once sparked debate as to the veracity of the tetramer has now shed light upon this new counterpart inαSyn *** magnetic resonance and computational studies on multimericαSyn structure have revealed that the protein folding propensity is controlled by small energy barriers that enable large scale ***,familial mutations ablate tetramerization and reconfigure polymorphic *** this review,we will discuss the dynamic landscape ofαSyn quaternary structure with a focus on the tetrameric conformation.

关键词： alpha-synuclein amyloid fibrils intrinsically disordered protein multimer N-acetylation oligomer Parkinson’s disease protein folding protein structure tetramer

Comparison of cross sectional optical coherence tomography images of elevated optic nerve heads across acquisition devices and scan protocols

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Eye and Vision 2018年第1期5卷 163-171页

作者： Megh d.Patel Fareshta Khushzad heather E.Moss department of Ophthalmology Stanford University2370 Watson Courtsuite 200Palo AltoCA 94303USA department of Neurology and Neurological Sciences Stanford University2370 Watson Courtsuite 200Palo AltoCA 94303USA

Background:Optic nerve head measurements extracted from optical coherence tomography(OCT)show promise for monitoring clinical conditions with elevated optic nerve *** aim of this study is to compare reliability within and between raters and between image acquisition devices of optic nerve measurements derived from OCT scans in eyes with varying degrees of optic nerve ***:Wide angle line scans and narrow angle radial scans through optic nerve heads were obtained using three spectral domain(Sd)OCT devices on 5 subjects(6 swollen optic nerves,4 normal optic nerves).Three raters independently semi-manually segmented the internal limiting membrane(ILM)and Bruch’s membrane(BM)on each scan using customized *** rater segmented each scan *** were qualitatively and quantitatively ***-rater,intra-rater and inter-device reliability was assessed for the optic nerve cross sectional area calculated from the ILM and BM segmentations using intraclass correlation coefficients and graphical ***:Line scans from all devices were qualitatively *** scans for which frame rate could not be adjusted were of lower ***-rater reliability for segmentation and optic nerve cross sectional area was better than inter-rater reliability,which was better than inter-device reliability,though all ICC exceeded *** was not impacted by the degree of optic nerve ***:Sd-OCT devices acquired similar quality scans of the optic nerve head,with choice of scan protocol affecting the *** image derived markers,variability between devices was greater than that attributable to inter and intra-rater differences.

关键词： Optic nerve head Optical coherence tomography Bruch’s membrane Inner limiting membrane Comparison

An examination of the population dynamics of syngnathid fishes within Tampa Bay,Florida,USA

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Current Zoology 2010年第1期56卷 118-133页

作者： heather d.MASONJONES Emily ROSE Lori Benson McRAE danielle L.dIXSON Biology department University of Tampa Biology department Texas A & M University School of Marine and Tropical Biology James Cook University

Seagrass ecosystems worldwide have been declining, leading to a decrease in associated fish populations, especially those with low mobility such as syngnathids （pipefish and seahorses）. This two-year pilot study investigated seasonal patterns in density, growth, site fidelity, and population dynamics of Tampa Bay （FL） syngnathid fishes at a site adjacent to two marinas under construction. Using a modified mark-recapture technique, fish were collected periodically from three closely located sites that varied in seagrass species （Thalassia spp., Syringodium spp., and mixed-grass sites） and their distance from open water, but had consistent physical/chemical environmental characteristics. Fish were marked, photographed for body size and gender measurements, and released the same day at the capture site. Of the 5695 individuals surveyed, 49 individuals were recaptured, indicating a large, flexible population. Population density peaks were observed in July of both years, with low densities in late winter and late summer. Spatially, syngnathid densities were highest closest to the mouth of the bay and lowest near the shoreline. Seven species of syngnathid fishes were observed, and species-specific patterns of seagrass use emerged during the study. However, only two species, Syngnathus scovelli and Hippoeampus zosterae, were observed at high frequencies. For these two species, body size decreased across the study period, but while S. scovelli＇s population density decreased, H. zosterae＇s increased. Across six of the seven species, population size declined over the course of this preliminary study; however, seasonal shifts were impossible to distinguish from potential anthropogenic effects of construction [Current Zoology 56 （1）： 118-133, 2010].

关键词： Syngnathids Habitat-use Seahorse Pipefish Population density Mark-recapture

Scattering and diffraction of plane P-waves in a 2-d elastic half-space Ⅱ：shallow arbitrary shaped canyon

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Earthquake Engineering and Engineering Vibration 2017年第3期16卷 459-485页

作者： heather P.Brandow Vincent Lee Civil and Environmental Engineering University of Southern California Los Angeles 90089 United States

Scattering and diffraction of elastic in-plane P-and SV-waves by a surface topography such as an elastic canyon at the surface of a half-space is a classical problem which has been studied by earthquake engineers and strong-motion seismologists for over forty years. The case of out-of-plane SH waves on the same elastic canyon that is semi-circular in shape on the half-space surface is the first such problem that was solved by analytic closed form solutions over forty years ago by Trifunac. The corresponding case of in-plane P-and SV-waves on the same circular canyon is a much more complicated problem because, the in-plane P-and SV-scattered waves have different wave speeds and together they must have zero normal and shear stresses at the half-space surface. It is not until recently in 2014 that analytic solution for such problem is found by the author in the work of Lee and Liu. This paper uses the technique of Lee and Liu of defining these stress-free scattered waves to solve the problem of the scattered and diffraction of these in-plane waves on an almost-circular surface canyon that is arbitrary in shape.

关键词： diffraction elastic P-waves SV-waves weighted-residual method arbitrary-shaped canyon

Impact of colorectal cancer screening participation in remote northern Canada:A retrospective cohort study

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World Journal of Gastroenterology 2020年第48期26卷 7652-7663页

作者： heather A Smith Andrew d Scarffe Nicole Brunet Cait Champion Kami Kandola Alisha Tessier Robin Boushey Craig Kuziemsky department of Surgery University of OttawaOttawa K1Y4E9OntarioCanada Telfer School of Management University of OttawaOttawa K1N6N5OntarioCanada Faculty of Medicine University of OttawaOttawa K1Y4E9OntarioCanada department of Surgery Northern Ontario School of MedicineSudbury P3E2C6OntarioCanada department of Health and Social Services Government of the Northwest TerritoriesYellowknife X1A1P5Northwest TerritoriesCanada department of Surgery Stanton Territorial Health AuthorityYellowknife X1A0H1Northwest TerritoriesCanada division of General Surgery University of OttawaOttawa K1H 8L6OntarioCanada Office of Research Services MacEwan UniversityEdmonton T5J4S2AlbertaCanada

BACKGROUNd Screening provides earlier colorectal cancer(CRC)detection and improves *** remains poorly understood if these benefits are realized with screening guidelines in remote northern populations of Canada where CRC rates are nearly twice the national average and access to colonoscopy is *** To evaluate the participation and impact of CRC screening guidelines in a remote northern *** This retrospective cohort study included residents of the Northwest Territories,a northern region of Canada,age 50-74 who underwent CRC screening by a fecal immunohistochemical test(FIT)between January 1,2014 to March 30,*** assess impact,individuals with a screen-detected CRC were compared to clinically-detected CRC cases for stage and location of CRC between *** assess participation,we conducted subgroup analyses of FIT positive individuals exploring the relationships between signs and symptoms of CRC at the time of screening,wait-times for colonoscopy,and screening *** sample Welch t-test was used for normally distributed continuous variables,Mann-Whitney-Wilcoxon Tests for data without normal distribution,and Chi-square goodness of fit test for categorical variables.A P value ofdered to be statistically *** 6817 fecal tests were completed,meaning an annual average screening rate of 25.04%,843(12.37%)were positive,629 individuals underwent a follow-up colonoscopy,of which,24.48%had advanced neoplasia(AN),5.41%had *** were no significant differences in stage,pathology,or location between screen-detected cancers and clinically-detected *** assessing participation and screening outcomes,we observed 49.51%of individuals referred for colonoscopy after FIT were ineligible for CRC screening,most often due to signs and symptoms of *** were more likely to have AN if they had signs and symptoms of cancer at the time of screening,waited over 180 d for colonoscopy,or were indigenous[

关键词： Gastroenterology Rural health services Public health Colorectal neoplasms Early detection of cancer Northwest Territories

Experimental repetitive mild traumatic brain injury induces deficits in trabecular bone microarchitecture and strength in mice

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Bone Research 2017年第4期5卷 357-366页

作者： Chandrasekhar Kesavan Nikita M Bajwa heather Watt Subburaman Mohan Musculoskeletal disease Center VA Loma Linda Healthcare SystemLama LindaCAUSA department of Medicine Loma DndaCAUSA department of Orthopedic Surgery Loma Linda UniversityLoma LindaCAUSA

To evaluate the long-term consequence of repetitive mild traumatic brain injury （mTBI） on bone, mTBI was induced in 10-week-old female C57BL/6J mice using a weight drop model, once per day for 4 consecutive days at different drop heights （0.5, 1 and 1.5 m） and the skeletal phenotype was evaluated at different time points after the impact. In vivo micro-CT （μ-CT） analysis of the tibial metaphysis at 2, 8 and 12 weeks after the impact revealed a 5%-32% reduction in trabecular bone mass. Histomorphometric analyses showed a reduced bone formation rate in the secondary spongiosa ofl.5 m impacted mice at 12 weeks post impact. Apparent modulus （bone strength）, was reduced by 30% （P 〈 0.05） at the proximal tibial metaphysis in the 1.5 m drop height group at 2 and 8 weeks post impact. Ex vivo μ-CT analysis of the fifth lumbar vertebra revealed a significant reduction in trabecular bone mass at 12 weeks of age in all three drop height groups. Serum levels of osteocalcin were decreased by 22%, 15%, and 19% in the 0.5, 1.0 and 1.5 m drop height groups, respectively, at 2 weeks post impact. Serum IGF-I levels were reduced by 18%-32% in mTBI mice compared to control mice at 2 weeks post impact. Serum osteocalcin and IGF-I levels correlated with trabecular BV/TV （r2 = 0.14 and 0.16, P 〈 0.05）. In conclusion, repetitive mTBI exerts significant negative effects on the trabecular bone microarchitecture and bone mechanical properties by influencing osteoblast function via reduced endocrine IGF-I actions.

关键词： IGF TBI Experimental repetitive mild traumatic brain injury induces deficits in trabecular bone microarchitecture and strength in mice

Applying robust design to study the effects of stratigraphic characteristics on brittle failure and bump potential in a coal mine

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International Journal of Mining Science and Technology 2018年第1期28卷 137-144页

作者： Bo-Hyun Kim Mark K.Larson heather E.Lawson Spokane Mining Research division NIOSH/CDC

Bumps and other types of dynamic failure have been a persistent, worldwide problem in the underground coal mining industry, spanning *** example, in just five states in the *** 1983 to 2014,there were 388 reportable *** significant advances in mine design tools and mining practices,these events continue to *** conditions have been associated with bump potential, such as the presence of stiff units in the local *** effect of a stiff sandstone unit on the potential for coal bumps depends on the location of the stiff unit in the stratigraphic column, the relative stiffness and strength of other structural members, and stress concentrations caused by *** study describes the results of a robust design to consider the impact of different lithologic risk factors impacting dynamic failure *** the inherent variability of stratigraphic characteristics in sedimentary formations,such as thickness, engineering material properties, and location, is significant and the number of influential parameters in determining a parametric study is large, it is impractical to consider every simulation case by varying each parameter ***, to save time and honor the statistical distributions of the parameters, it is necessary to develop a robust design to collect sufficient sample data and develop a statistical analysis method to draw accurate conclusions from the collected *** this study,orthogonal arrays, which were developed using the robust design, are used to define the combination of the(a) thickness of a stiff sandstone inserted on the top and bottom of a coal seam in a massive shale mine roof and floor,(b) location of the stiff sandstone inserted on the top and bottom of the coal seam,and(c) material properties of the stiff sandstone and contacts as interfaces using the 3-dimensional numerical model, *** completion of the numerical experiments, statistical and multivariate analysis are performed using

关键词： Bumps Robust design FLAC3d Plastic dissipated energy Multiple regression

Weighted residual method for diffraction of plane P-waves in a 2-d elastic half-spaceⅢ:on an almost circular arbitrary-shaped alluvial valley

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Earthquake Science 2018年第1期31卷 19-34页

作者： heather P.Brandow Vincent Lee Brandow&Nastar Inc. Rancho Santa MargaritaCA 92688USA Asanti Civil Environmental Engineering University of Southern CaliforniaLos AngelesCA 90089-2531USA

Scattering and diffraction of elastic in-plane P- and SV-waves by a surface topography such as an elastic canyon at the surface of a half-space is a classical problem which has been studied by earthquake engineers and strong motion seismologists for over forty years. The case of out-of- plane SH-waves on the same elastic canyon that is semicircular in shape on the half-space surface is the first such problem that was solved by analytic closed-form solutions over forty years ago by Trifunac. The corresponding case of in-plane P- and SV- waves on the same circular canyon is a much more complicated problem because the in-plane P- and SV- scattered waves have different wave speeds and together they must have zero normal and shear stresses at the half-space surface. It is not until recently in 2014 that analytic solution for such problem is found by Lee and Liu. This paper uses their technique of defining these stress-free scattered waves, which Brandow and Lee previously used to solve the problem of the scattering and diffraction of these in-plane waves on an almost-circular surface canyon that is arbitrary in shape, to the study of the scattering and diffraction of these in-plane waves on an almost circular arbitrary-shaped alluvial valley.

关键词： Scattering diffraction Alluvial valley Arbitrary shaped Weighted-residues Amplification

Revealing the identity of regulatory T-cell-suppressed self-reactive Cd4^(+)T cells

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Cellular & Molecular Immunology 2023年第10期20卷 1093-1094页

作者： Judith N.Mandl heather J.Melichar department of Physiology and McGill Research Centre on Complex Traits McGill UniversityMontrealQCCanada Immunology-Oncology Unit Maisonneuve-Rosemont Hospital Research CenterMontrealQCCanada department of Medicine Universitéde MontréalMontrealQCCanada

A recent study published in Nature Immunology by Peter Savage and colleagues sought to characterize regulatory T-cell(Treg)-suppressed self-reactive Cd4^(+)T cells using an elegant system combining the depletion of Tregs with T-cell receptor(TCR)sequencing of expanded conventional Cd4^(+)T-cell *** tracking the fate of T cells engineered to express the identified TCRs,Lee et *** a‘new’subpopulation of Cd4^(+)T cells bearing antigen receptors with high levels of self-reactivity that take on a T follicular helper(TFH)-like phenotype in the periphery in the absence of immune challenge[1].Antigen-specificαβTCRs are generated through the somatic recombination of V(d)J gene segments during thymic development,giving rise to T cells that can recognize an enormously diverse set of peptides presented by major histocompatibility complex(pMHC)molecules.A risk of this process is that it can also lead to the generation of potentially highly self-reactive TCRs.T cells with TCRs with high affinity for self-pMHC molecules are purged in the thymus by clonal deletion,a key tolerance mechanism that prevents ***,this process is incomplete,and highly self-reactive T cells can escape negative selection and join the peripheral naive T-cell ***,while the naive Cd4^(+)T-cell pool is heterogeneous with regard to an individual T cell’s reactivity for self-pMHC molecules,the distribution of T cells with differing strengths of self-reactivity leaving the thymus is skewed toward those with relatively higher self-pMHC binding strengths[2].A subset of these highly self-reactive Cd4^(+)T cells in the periphery are deleted,some become functionally anergic,and others differentiate into Tregs,which go on to play an important role in peripheral tolerance,holding other Cd4^(+)T cells with potentially dangerous levels of self-reactivity in check[3].What is the fate of these Treg-suppressed self-reactive cells?

关键词： reactivity incomplete expanded