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Method to assess component contribution to toxicity of complex mixtures： Assessment of puberty acquisition in rats exposed to disinfection byproducts

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Journal of Environmental Sciences 2017年第8期29卷 311-321页

作者： Shahid Parvez glenn E.Rice Linda K.Teuschler Jane Ellen Simmons Thomas F.Speth Susan D.Richardson Richard J.Miltner E.Sidney Hunter Ⅲ Jonathan g.Pressman Lillian F.Strader gary R.Klinefelter Jerome M.goldman michael g.narotsky Indiana University Richard M. Fairbanks School of Public Health Department of Environmental Health Sciences IUPUI Campus Indianapolis IN 46202 USA National Center for Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency Cincinnati OH 45268 USA Lincla Teuschler and Associates St. Petersburg FL 33707 USA National Health and Environmental Effects Research Laboratory Office of Research and Development U.S. Environmental Protection Agency Research Triangle Park NC 27711 USA National Risk Management Research Laboratory Office of Research and Development U.S. Environmental Protection Agency Cincinnati OH 45268 USA Department of Chemistry and Biochemistry University of South Carolina Columbia SC 29208 USA

A method based on regression modeling was developed to discern the contribution of component chemicals to the toxicity of highly complex, environmentally realistic mixtures of disinfection byproducts（DBPs）. Chemical disinfection of drinking water forms DBP *** of concerns about possible reproductive and developmental toxicity, a whole mixture（WM） of DBPs produced by chlorination of a water concentrate was administered as drinking water to Sprague–Dawley（S–D） rats in a multigenerational study. Age of puberty acquisition,i.e., preputial separation（PPS） and vaginal opening（VO）, was examined in male and female offspring, respectively. When compared to controls, a slight, but statistically significant delay in puberty acquisition was observed in females but not in males. WM-induced differences in the age at puberty acquisition were compared to those reported in S–D rats administered either a defined mixture（DM） of nine regulated DBPs or individual DBPs. Regression models were developed using individual animal data on age at PPS or VO from the DM study. Puberty acquisition data reported in the WM and individual DBP studies were then compared with the DM models. The delay in puberty acquisition observed in the WM-treated female rats could not be distinguished from delays predicted by the DM regression model, suggesting that the nine regulated DBPs in the DM might account for much of the delay observed in the WM. This method is applicable to mixtures of other types of chemicals and other endpoints.

关键词： Drinking water disinfection byproducts DBP Puberty delay Four Lab Study Mixtures risk assessment

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Resident immune responses to spinal cord injury:role of astrocytes and microglia

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Neural Regeneration Research 2024年第8期19卷 1678-1685页

作者： Sydney Brockie Cindy Zhou michael g.Fehlings Division of genetics and Development Krembil Research InstituteUniversity Health NetworkTorontoONCanada Institute of Medical Science University of TorontoTorontoONCanada Division of Neurosurgery and Spine Program Department of SurgeryUniversity of TorontoTorontoONCanada

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our *** r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal *** makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative *** these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory *** review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after ***,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural *** the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous *** advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are *** key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

关键词： astrocytes glial signaling microglia spinal cord injury synaptic transmission

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Multiple sclerosis drug repurposing for neuroregeneration

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Neural Regeneration Research 2024年第3期19卷 507-508页

作者： Peter göttle michael Dietrich Patrick Küry Department of Neurology Medical FacultyHeinrich-Heine UniversityDüsseldorfGermany

Multiple sclerosis(MS)is an autoimmune disorder of the central nervous system(CNS)and is primarily characterized by immune cell infiltration leading to relapses followed by remission phases and a disease course turning progressive over time with neurodegenerative processes taking over(Amin and Hersh,2023).Of note,beyond relapse-associated worsening early in disease progression independent of relapse activity may arise independently of relapse activity and can occur in all ***-mediated damage of myelin sheaths and the subsequent loss of mature oligodendrocytes are resulting in impaired axonal integrity,neurodegeneration and accounts for irreversible neuronal damage(Kuhlmann et al.,2023).The current landscape of available disease-modifying therapies comprises mainly immunomodulatory drugs that effectively diminish relapses and slow down progression at the onset form of the disease,namely relapsing MS(RMS).In this regard,a number of drugs have been approved as disease-modifying therapies for MS by US Food and Drug Administration and European Medicines Agencies(Box 1).

关键词： drugs impaired irreversible

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Use of an immunocapture device to detect cytokine release in discrete brain regions

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Neural Regeneration Research 2024年第4期19卷 703-704页

作者： Matthew g.Frank michael V.Baratta Department of Integrative Physiology University of Colorado BoulderBoulderCOUSA(Frank MG)Department of Psychology and NeuroscienceUniversity of Colorado BoulderBoulderCOUSA(Baratta MV)

Production of proinflammatory cytokines in the central nervous system is a key process in the neuroinflammatory response to trauma,infection,and neurodegenerative diseases(Kumar,2019).These intercellular signaling molecules play multiple roles in the immune response in the central nervous system including the orchestration of the sickness response to innate immune perturbations in the brain(Dantzer et al.,2008).

关键词： system release innate

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A randomized,controlled,open label non-inferiority trial of intravenous ferric carboxymaltose versus iron sucrose in patients with iron deficiency anemia in China

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Frontiers of Medicine 2024年第1期18卷 98-108页

作者： Jie Jin Zhihua Ran Emanuele Noseda Bernard Roubert Matthieu Marty Anna Mezzacasa Udo michael göring The First Affiliated Hospital Zhejiang University College of MedicineHangzhou310058China Renji Hospital Shanghai Jiao Tong University School of MedicineShanghai200025China Vifor Pharma Glattbrugg8152Switzerland

Iron deficiency(ID)and ID anemia(IDA)pose significant public health concerns in *** iron sucrose(IS)treatment is well-established in the country,ferric carboxymaltose(FCM)offers the advantage of higher doses and fewer *** open label,randomized,controlled,non-inferiority trial was conducted at multiple sites in China to compare the outcomes of FCM(maximum of 2 doses,500 or 1000 mg iron)and IS(up to 11 infusions,200 mg iron)treatments in subjects with *** primary endpoint was the achievement of hemoglobin(Hb)response(an increase of⩾2 g/dL from baseline)within 8 weeks,whereas secondary endpoints included changes in Hb,transferrin saturation,and serum ferritin *** the 371 randomized subjects,a similar percentage of subjects treated with FCM and IS achieved Hb-response(FCM 99.4%,IS 98.3%),thereby confirming the non-inferiority of FCM compared with IS(difference 1.12(−2.15,4.71;95%confidence interval(CI))).Furthermore,a significantly higher proportion of FCM-treated subjects achieved early Hb-response at Week 2(FCM 85.2%,IS 73.2%;difference 12.1(3.31,20.65;95%CI)).Additionally,the increase in TSAT and serum ferritin levels from baseline was significantly greater at all time points for FCM-treated *** safety profiles of FCM and IS were comparable,with the exception of transient hypophosphatemia and pyrexia,which are consistent with FCM’s known safety *** conclusion,FCM proves to be an efficacious treatment for IDA,providing faster Hb-response and correction of ID with fewer administrations than IS.

关键词： iron deficiency anemia intravenous iron ferric carboxymaltose iron sucrose Hb response early response

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Neuronal trafficking as a key to functional recovery in immune-mediated neuropathies

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Neural Regeneration Research 2024年第11期19卷 2331-2332页

作者： Felix Kohle michael Schroeter Department of Neurology University of Cologne and University Hospital CologneCologneGermany

Immune-mediated neuropathies are rare diseases of the peripheral nervous system(PNS),substantially affecting patients’functionality and quality of *** are amenable to immunomodulatory treatments,which in many cases stabilize disease progression,but long-term deficits persist in many *** long-term deficits are particularly observed in monophasic autoimmune neuropathies like guillain-Barrésyndrome and also in chronic variants,e.g.,chronic inflammatory demyelinating neuropathy(Fadia et al.,2019).

关键词： diseases autoimmune

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Implementation and validation of a bonded particle model to predict rheological properties of viscoelastic materials

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Particuology 2024年第6期89卷 198-210页

作者： michael Mascara Arno Mayrhofer Stefan Radl Christoph Kloss Institute of Process and Particle Engineering Graz University of TechnologyInffeldgasse 13Graz8010Austria DCS Computing gmbH Industriezeile 35Linz4020Austria

This work focuses on implementing a particle-based method able to characterize viscoelastic materials whose rheological properties,such as storage modulus g′and loss modulus g″,are *** is based on the bonded particle model,with the elastic constitutive relation here substituted with a viscoelastic one to capture time-scale *** Burgers model,vastly used in literature to model viscoelastic systems,is discretized and *** test case used for calibration comprises of a cubic lattice,sheared with a periodic motion,to mimic the effect of a shear *** appropriate filtering of the stress response,the rheological properties are obtained,highlighting the effect of the lattice geometry,as well as the particle size,on the accuracy of the ***,the Burgers parameters are calibrated by analytically fitting the experimental dataset,showing the limitation of the Burgers *** micro-contact parameters are obtained from the macro parameters through appropriate *** completing a frequency sweep,the simulated g′and g″show a relatively large error,around 25%for g’for *** this reason,a more robust model,namely the generalized Maxwell model,has been *** calibration procedure is performed in the same fashion as for the Burgers ***,the tangential micro-contact parameters are scaled *** normal *** scaling parameter,calledα,is calibrated by minimizing the root mean square error between simulation and experimental data,giving errors below 10%in both g′and g″for a large ***,a full ring plate-plate rheometer setup is simulated,and the simulation is compared with the given experimental dataset,again finding a good agreement.

关键词： DEM Rheology Numerical modeling Viscoelasticity

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Nonparametric Feature Screening via the Variance of the Regression Function

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Open Journal of Statistics 2024年第4期14卷 413-438页

作者： Won Chul Song michael g. Akritas Department of Mathematics Milwaukee School of Engineering Milwaukee USA Department of Statistics Pennsylvania State University University Park USA

This article develops a procedure for screening variables, in ultra high-di- mensional settings, based on their predictive significance. This is achieved by ranking the variables according to the variance of their respective marginal regression functions (RV-SIS). We show that, under some mild technical conditions, the RV-SIS possesses a sure screening property, which is defined by Fan and Lv (2008). Numerical comparisons suggest that RV-SIS has competitive performance compared to other screening procedures, and outperforms them in many different model settings.

关键词： Sure Independence Screening Nonparametric Regression Ultrahigh-Dimensional Data Variable Selection

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Challenges and opportunities in the production of magnesium parts by directed energy deposition processes

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Journal of Magnesium and Alloys 2024年第5期12卷 1663-1686页

作者： gürel Cam Ali günen Iskenderun Technical University Faculty of Engineering and Natural SciencesDepartment of Mechanical Engineering31200 Iskenderun-HatayTurkey Iskenderun Technical University Faculty of Engineering and Natural SciencesDepartment of Metallurgy and Materials Engineering31200 Iskenderun-HatayTurkey

Mg-alloys have gained considerable attention in recent years for their outstanding properties such as lightweight,high specific strength,and corrosion resistance,making them attractive for applications in medical,aerospace,automotive,and other transport ***,their widespread application is hindered by their low formability at room temperature due to limited slip *** Mg-alloys have low mechanical properties due to the presence of casting defects such as porosity and anisotropy in addition to the high *** casting methods benefit from established process optimization techniques for these problems,additive manufacturing methods are increasingly replacing casting methods in Mg alloys as they provide more precise control over the microstructure and allow specific grain orientations,potentially enabling easier optimization of anisotropy properties in certain *** metal additive manufacturing(MAM)technology also results in some manufacturing defects such as inhomogeneous microstructural evolution and porosity and additively manufactured Mg alloy parts exhibit lower properties than the wrought parts,they in general exhibit superior properties than the cast ***,MAM is a promising technique to produce Mg alloy *** energy deposition processes,particularly wire arc directed energy deposition(WA-DED),have emerged as an advantageous additive manufacturing(AM)technique for metallic materials including magnesium alloys,offering advantages such as high deposition rates,improved material efficiency,and reduced production costs compared to subtractive ***,the inherent challenges associated with magnesium,such as its high reactivity and susceptibility to oxidation,pose unique hurdles in the application of this *** review paper delves into the progress made in the application of DED technology to Mg-alloys,its challenges,and ***,the predominant imperfections,notably inhomo

关键词： Additive manufacturing DED processes Arc-DED Wire arc additive manufacturing(WAAM) 3-D printing High deposition rate

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Iterative Subregion Correction Preconditioners with Adaptive Tolerance for Problems with geometrically Localized Stiffness

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Communications on Applied Mathematics and Computation 2024年第2期6卷 811-836页

作者： michael Franco Per-Olof Persson Will Pazner Department of Mathematics University of CaliforniaBerkeleyBerkeleyCA 94720-3840USA Fariborz Maseeh Department of Mathematics and Statistics Portland State UniversityPortlandOR 97201USA

We present a class of preconditioners for the linear systems resulting from a finite element or discontinuous galerkin discretizations of advection-dominated *** preconditioners are designed to treat the case of geometrically localized stiffness,where the convergence rates of iterative methods are degraded in a localized subregion of the *** convergence may be caused by a number of factors,including the mesh size,anisotropy,highly variable coefficients,and more challenging *** approach taken in this work is to correct well-known preconditioners such as the block Jacobi and the block incomplete LU(ILU)with an adaptive inner subregion *** goal of these preconditioners is to reduce the number of costly global iterations by accelerating the convergence in the stiff region by iterating on the less expensive reduced *** tolerance for the inner iteration is adaptively chosen to minimize subregion-local work while guaranteeing global convergence *** present analysis showing that the convergence of these preconditioners,even when combined with an adaptively selected tolerance,is independent of discretization parameters(e.g.,the mesh size and diffusion coefficient)in the *** demonstrate significant performance improvements over black-box preconditioners when applied to several model convection-diffusion ***,we present performance results of several variations of iterative subregion correction preconditioners applied to the Reynolds number 2.25×10^(6)fluid flow over the NACA 0012 airfoil,as well as massively separated flow at 30°angle of attack.

关键词： Subregion correction Nested Krylov geometrically localized stiffness

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