133 research outputs found

    Alzheimer’s disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology

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    Introduction: Cerebrospinal fluid (CSF) biomarkers, although of established utility in the diagnostic evaluation of Alzheimer's disease (AD), are known to be sensitive to variation based on pre-analytical sample processing. We assessed whether gravity droplet collection versus syringe aspiration was another factor influencing CSF biomarker analyte concentrations and reproducibility. Methods: Standardized lumbar puncture using small calibre atraumatic spinal needles and CSF collection using gravity fed collection followed by syringe aspirated extraction was performed in a sample of elderly individuals participating in a large long-term observational research trial. Analyte assay concentrations were compared. Results: For the 44 total paired samples of gravity collection and aspiration, reproducibility was high for biomarker CSF analyte assay concentrations (concordance correlation [95%CI]: beta-amyloid1-42 (Aβ42) 0.83 [0.71 - 0.90]), t-tau 0.99 [0.98 - 0.99], and phosphorylated tau (p-tau) 0.82 [95 % CI 0.71 - 0.89]) and Bonferroni corrected paired sample t-tests showed no significant differences (group means (SD): Aβ42 366.5 (86.8) vs 354.3 (82.6), p = 0.10; t-tau 83.9 (46.6) vs 84.7 (47.4) p = 0.49; p-tau 43.5 (22.8) vs 40.0 (17.7), p = 0.05). The mean duration of collection was 10.9 minutes for gravity collection and <1 minute for aspiration. Conclusions: Our results demonstrate that aspiration of CSF is comparable to gravity droplet collection for AD biomarker analyses but could considerably accelerate throughput and improve the procedural tolerability for assessment of CSF biomarkers

    Nucleation and growth of biomimetic apatite layers on 3D plotted biodegradable polymeric scaffolds : effect of static and dynamic coating conditions

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    Apatite layers were grown on the surface of newly developed starch/polycaprolactone (SPCL)-based scaffolds by a 3D plotting technology. To produce the biomimetic coatings, a sodium silicate gel was used as nucleating agent, followed by immersion in a simulated body fluid (SBF) solution. After growing a stable apatite layer for 7 days, the scaffolds were placed in SBF under static, agitated (80 strokes min!1) and circulating flow perfusion (Q = 4 ml min!1; tR = 15 s) for up to 14 days. The materials were characterized by scanning electron microscopy/energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy and thin-film X-ray diffraction. Cross-sections were obtained and the coating thickness was measured. The elemental composition of solution and coatings was monitored by inductively coupled plasma spectroscopy. After only 6 h of immersion in SBF it was possible to observe the formation of small nuclei of an amorphous calcium phosphate (ACP) layer. After subsequent SBF immersion from 7 to 14 days under static, agitated and circulating flow perfusion conditions, these layers grew into bone-like nanocrystalline carbonated apatites covering each scaffold fiber without compromising its initial morphology. No differences in the apatite composition/chemical structure were detectable between the coating conditions. In case of flow perfusion, the coating thickness was significantly higher. This condition, besides mimicking better the biological milieu, allowed for the coating of complex architectures at higher rates, which can greatly reduce the coating step.The authors acknowledge the Portuguese Foundation for Science and Technology (PhD grant to A.L.O., SFRH/BD/10956/2002 and post-doctoral Grant to R.A.S., SFRH/BPD/17151/2004, under the POCTI Program). This work was partially supported by FCT through POCTI and/or FEDER programmes and also partially supported by the EU Project HIPPOCRATES (NMP3-CT-2003-505758) and EXPERTISSUES (NMP-CT-2004-500283)

    Genetic loci regulate Sarbecovirus pathogenesis: A comparison across mice and humans

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    Coronavirus (CoV) cause considerable morbidity and mortality in humans and other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) in 2003, Middle East Respiratory CoV (MERS-CoV) in 2012, and SARS-CoV-2 in 2019. Although poorly characterized, natural genetic variation in human and other mammals modulate virus pathogenesis, as reflected by the spectrum of clinical outcomes ranging from asymptomatic infections to lethal disease. Using multiple human epidemic and zoonotic Sarbecoviruses, coupled with murine Collaborative Cross genetic reference populations, we identify several dozen quantitative trait loci that regulate SARS-like group-2B CoV pathogenesis and replication. Under a Chr4 QTL, we deleted a candidate interferon stimulated gene, Trim14 which resulted in enhanced SARS-CoV titers and clinical disease, suggesting an antiviral role during infection. Importantly, about 60 % of the murine QTL encode susceptibility genes identified as priority candidates from human genome-wide association studies (GWAS) studies after SARS-CoV-2 infection, suggesting that similar selective forces have targeted analogous genes and pathways to regulate Sarbecovirus disease across diverse mammalian hosts. These studies provide an experimental platform in rodents to investigate the molecular-genetic mechanisms by which potential cross mammalian susceptibility loci and genes regulate type-specific and cross-SARS-like group 2B CoV replication, immunity, and pathogenesis in rodent models. Our study also provides a paradigm for identifying susceptibility loci for other highly heterogeneous and virulent viruses that sporadically emerge from zoonotic reservoirs to plague human and animal populations

    Analytical solutions for wall slip effects on magnetohydrodynamic oscillatory rotating plate and channel flows in porous media using a fractional burgers viscoelastic model

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    A theoretical analysis of magnetohydrodynamic (MHD) incompressible flows of Burger's fluid through a porous medium in a rotating frame of reference is presented. The constitutive model of a Burger's fluid is used based on a fractional calculus formulation. Hydrodynamic slip at the wall (plate) is incorporated and a fractional generalized Darcy model deployed to simulate porous medium drag force effects. Three different cases are considered- namely, flow induced by a general periodic oscillation at a rigid plate, periodic flow in a parallel plate channel and finally Poiseuille flow. In all cases the plate (s) boundary (ies) are electrically-non-conducting and small magnetic Reynolds is assumed, negating magnetic induction effects. The well-posed boundary value problems associated with each case are solved via Fourier transforms. Comparisons are made between the results derived with and without slip conditions. 4 special cases are retrieved from the general fractional Burgers model, viz Newtonian fluid, general Maxwell viscoelastic fluid, generalized Oldroyd-B fluid and the conventional Burger’s viscoelastic model. Extensive interpretation of graphical plots is included. We study explicitly the influence on wall slip on primary and secondary velocity evolution. The model is relevant to MHD rotating energy generators employing rheological working fluids

    Search for the Chiral Magnetic Effect in Au+Au collisions at sNN=27\sqrt{s_{_{\rm{NN}}}}=27 GeV with the STAR forward Event Plane Detectors

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    A decisive experimental test of the Chiral Magnetic Effect (CME) is considered one of the major scientific goals at the Relativistic Heavy-Ion Collider (RHIC) towards understanding the nontrivial topological fluctuations of the Quantum Chromodynamics vacuum. In heavy-ion collisions, the CME is expected to result in a charge separation phenomenon across the reaction plane, whose strength could be strongly energy dependent. The previous CME searches have been focused on top RHIC energy collisions. In this Letter, we present a low energy search for the CME in Au+Au collisions at sNN=27\sqrt{s_{_{\rm{NN}}}}=27 GeV. We measure elliptic flow scaled charge-dependent correlators relative to the event planes that are defined at both mid-rapidity ∣Ρ∣<1.0|\eta|<1.0 and at forward rapidity 2.1<∣Ρ∣<5.12.1 < |\eta|<5.1. We compare the results based on the directed flow plane (Ψ1\Psi_1) at forward rapidity and the elliptic flow plane (Ψ2\Psi_2) at both central and forward rapidity. The CME scenario is expected to result in a larger correlation relative to Ψ1\Psi_1 than to Ψ2\Psi_2, while a flow driven background scenario would lead to a consistent result for both event planes[1,2]. In 10-50\% centrality, results using three different event planes are found to be consistent within experimental uncertainties, suggesting a flow driven background scenario dominating the measurement. We obtain an upper limit on the deviation from a flow driven background scenario at the 95\% confidence level. This work opens up a possible road map towards future CME search with the high statistics data from the RHIC Beam Energy Scan Phase-II.Comment: main: 8 pages, 5 figures; supplementary material: 2 pages, 1 figur

    Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

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    Alignment of the CMS silicon tracker during commissioning with cosmic rays

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    This is the Pre-print version of the Article. The official published version of the Paper can be accessed from the link below - Copyright @ 2010 IOPThe CMS silicon tracker, consisting of 1440 silicon pixel and 15 148 silicon strip detector modules, has been aligned using more than three million cosmic ray charged particles, with additional information from optical surveys. The positions of the modules were determined with respect to cosmic ray trajectories to an average precision of 3–4 microns RMS in the barrel and 3–14 microns RMS in the endcap in the most sensitive coordinate. The results have been validated by several studies, including laser beam cross-checks, track fit self-consistency, track residuals in overlapping module regions, and track parameter resolution, and are compared with predictions obtained from simulation. Correlated systematic effects have been investigated. The track parameter resolutions obtained with this alignment are close to the design performance.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

    Commissioning and performance of the CMS pixel tracker with cosmic ray muons

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    This is the Pre-print version of the Article. The official published verion of the Paper can be accessed from the link below - Copyright @ 2010 IOPThe pixel detector of the Compact Muon Solenoid experiment consists of three barrel layers and two disks for each endcap. The detector was installed in summer 2008, commissioned with charge injections, and operated in the 3.8 T magnetic field during cosmic ray data taking. This paper reports on the first running experience and presents results on the pixel tracker performance, which are found to be in line with the design specifications of this detector. The transverse impact parameter resolution measured in a sample of high momentum muons is 18 microns.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)
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