Material characterisation for discrete element modelling calibration

The accurate determination of the microparameters needed in a Discrete Element Method (DEM) simulation is essential to obtain reliable results. In this work the DEM model parameters sensitivity in three different laboratory tests (single particle drop test, uniaxial particle compression and rotating drum) are investigated with respect to parameter value changes. The DEM parameters are varied by ± 25% from standard values. Materials used are 3.0 mm soda lime glass spheres and 3.0 mm polyamide spheres. Drop test simulations were sensitive only to change in coefficient of restitution parameter. The single particle compression test indicates that mainly the elasticity parameters influence the numerical response, Young’s modulus and Poisson’s ratio respectively. The sensitivity analysis indicates that the dynamic angle of repose in simulations depends on static as well as rolling friction coefficients

Diking, young volcanism and diffuse hydrothermal activity on the southern Mid-Atlantic Ridge: The Lilliput field at 9°33'S

Detailed exploration with remotely operated and autonomous deep submergence vehicles has revealed, at 9 degrees 33'S, the presence of the southernmost active hydrothermal field known so far on the Mid-Atlantic Ridge. The size of the hydrothermal field, which we have named "Lilliput", is about 1000 m x 250 m. It lies in a water depth of 1500 m on a ridge segment (Segment A3) with considerably thickened crust of 11 km. Four relatively small diffuse vent sites occur on a large young (estimated <100 years old) lava flow, partly covering the flow with hydrothermal Fe-oxide/hydroxide sediments. Based on homogeneous major element compositions of ca. 25 lava samples, this flow covers an area of at least 5 km x 0.6 km. The lava flow erupted from a series of parallel fissures at the western edge of the flow and a volcanic ridge consisting of up to 30 m high pillow mounds. The volcanic ridge probably represents the surface expression of an underlying dike which fed the flow. Several drained lava pond structures were observed within the flow but only one shows hydrothermal activity. The hydrothermal venting and precipitation of abundant Fe-oxyhydroxides appear to be related to the young diking and eruption event and the four different hydrothermally active sites of the Lilliput field lie along and almost equidistant from the eastern flank of the supposed dike. Although a hydrothermal plume some 500 m above the seafloor was found in two consecutive years (2005 and 2006), no high-temperature venting associated with Lilliput has been found. in agreement with findings at other ridges with thick crust such as Reykjanes. High magma supply rate and frequent diking and eruption events may lead to hot hydrothermal vents being rare in slow-spreading segments with thick crust whereas diffuse venting is abundant. Interestingly, the fauna at the Lilliput vents largely consists of small and apparently juvenile mussels (Bathymodiolus sp.) and did not show any signs of growth during the four years of continuing observations possibly reflecting pulsing hydrothermal activity

Comparing cortical signatures of atrophy between late-onset and autosomal dominant Alzheimer disease

Defining a signature of cortical regions of interest preferentially affected by Alzheimer disease (AD) pathology may offer improved sensitivity to early AD compared to hippocampal volume or mesial temporal lobe alone. Since late-onset Alzheimer disease (LOAD) participants tend to have age-related comorbidities, the younger-onset age in autosomal dominant AD (ADAD) may provide a more idealized model of cortical thinning in AD. To test this, the goals of this study were to compare the degree of overlap between the ADAD and LOAD cortical thinning maps and to evaluate the ability of the ADAD cortical signature regions to predict early pathological changes in cognitively normal individuals. We defined and analyzed the LOAD cortical maps of cortical thickness in 588 participants from the Knight Alzheimer Disease Research Center (Knight ADRC) and the ADAD cortical maps in 269 participants from the Dominantly Inherited Alzheimer Network (DIAN) observational study. Both cohorts were divided into three groups: cognitively normal controls (nADRC = 381; nDIAN = 145), preclinical (nADRC = 153; nDIAN = 76), and cognitively impaired (nADRC = 54; nDIAN = 48). Both cohorts underwent clinical assessments, 3T MRI, and amyloid PET imaging with either 11C-Pittsburgh compound B or 18F-florbetapir. To generate cortical signature maps of cortical thickness, we performed a vertex-wise analysis between the cognitively normal controls and impaired groups within each cohort using six increasingly conservative statistical thresholds to determine significance. The optimal cortical map among the six statistical thresholds was determined from a receiver operating characteristic analysis testing the performance of each map in discriminating between the cognitively normal controls and preclinical groups. We then performed within-cohort and cross-cohort (e.g. ADAD maps evaluated in the Knight ADRC cohort) analyses to examine the sensitivity of the optimal cortical signature maps to the amyloid levels using only the cognitively normal individuals (cognitively normal controls and preclinical groups) in comparison to hippocampal volume. We found the optimal cortical signature maps were sensitive to early increases in amyloid for the asymptomatic individuals within their respective cohorts and were significant beyond the inclusion of hippocampus volume, but the cortical signature maps performed poorly when analyzing across cohorts. These results suggest the cortical signature maps are a useful MRI biomarker of early AD-related neurodegeneration in preclinical individuals and the pattern of decline differs between LOAD and ADAD.Fil: Dincer, Aylin. Washington University in St. Louis; Estados UnidosFil: Gordon, Brian A.. Washington University in St. Louis; Estados UnidosFil: Hari-Raj, Amrita. Ohio State University; Estados UnidosFil: Keefe, Sarah J.. Washington University in St. Louis; Estados UnidosFil: Flores, Shaney. Washington University in St. Louis; Estados UnidosFil: McKay, Nicole S.. Washington University in St. Louis; Estados UnidosFil: Paulick, Angela M.. Washington University in St. Louis; Estados UnidosFil: Shady Lewis, Kristine E.. University of Kentucky; Estados UnidosFil: Feldman, Rebecca L.. Washington University in St. Louis; Estados UnidosFil: Hornbeck, Russ C.. Washington University in St. Louis; Estados UnidosFil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Ances, Beau M.. Washington University in St. Louis; Estados UnidosFil: Berman, Sarah B.. University of Pittsburgh; Estados UnidosFil: Brickman, Adam M.. Columbia University; Estados UnidosFil: Brooks, William S.. Neuroscience Research Australia; Australia. University of New South Wales; AustraliaFil: Cash, David M.. UCL Queen Square Institute of Neurology; Reino UnidoFil: Chhatwal, Jasmeer P.. Harvard Medical School; Estados UnidosFil: Farlow, Martin R.. Indiana University; Estados UnidosFil: Fougère, Christian la. German Center for Neurodegenerative Diseases; Alemania. University Hospital of Tübingen; AlemaniaFil: Fox, Nick C.. UCL Queen Square Institute of Neurology; Reino UnidoFil: Fulham, Michael J.. Royal Prince Alfred Hospital; Australia. University of Sydney; AustraliaFil: Jack, Clifford R.. Mayo Clinic; Estados UnidosFil: Joseph-Mathurin, Nelly. Washington University in St. Louis; Estados UnidosFil: Karch, Celeste M.. Washington University in St. Louis; Estados UnidosFil: Lee, Athene. University Brown; Estados UnidosFil: Levin, Johannes. German Center for Neurodegenerative Diseases; Alemania. Ludwig Maximilians Universitat; Alemania. Munich Cluster for Systems Neurology; AlemaniaFil: Masters, Colin L.. University of Melbourne; AustraliaFil: McDade, Eric M.. Washington University in St. Louis; Estados UnidosFil: Oh, Hwamee. University Brown; Estados UnidosFil: Perrin, Richard J.. Washington University in St. Louis; Estados Unido

Preparation of azide biosynthetic surrogates of myo-Inositol

As a prelude to biomolecular incorporation studies, practical routes to a series of four regioisomeric azido-deoxy derivatives of inositol that mimic the natural myo-stereochemistry are described. Starting from commercially available myo-inositol, the regioselective and stereoselective introduction of azide functionality was achieved at the C-2, C-3, C-4 and C-5 positions via azide displacement of the corresponding O-sulfonates of suitably protected scyllo-, chiro-, epi- and neo-inositols, respectively. Notably, a final one-pot acetolysis method conveniently allowed for rapid access to pentaacetate azido-deoxy inositols. Investigations on the metabolic incorporation of these myo-inositol azide surrogates in both acetate and free alcohol forms are in progress

Geochemistry of abyssal peridotites (Mid-Atlantic Ridge, 15°20′N, ODP Leg 209) : implications for fluid/rock interaction in slow spreading environments

Author Posting. © Elsevier B.V., 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Chemical Geology 234 (2006): 179-210, doi:10.1016/j.chemgeo.2006.04.011.Abyssal peridotite from the 15°20’N area of the Mid-Atlantic Ridge show complex geochemical variations among the different sites drilled during ODP Leg 209. Major element compositions indicate variable degrees of melt depletion and refertilization as well as local hydrothermal metasomatism. Strongest evidence for melt-rock interactions are correlated Light Rare Earth Element (LREE) and High Field Strength Element (HFSE) additions at sites 1270 and 1271. In contrast, hydrothermal alteration at Sites 1274, 1272, and 1268 causes LREE mobility associated with minor HFSE variability, reflecting the low solubility of HFSE in aqueous solutions. Site 1274 contains the least-altered, highly refractory, peridotite with strong depletion in LREE and shows a gradual increase in the intensity of isochemical serpentinization; except for the addition of H2O which causes a mass gain of up to 20 g/100 g. The formation of magnetite is reflected in decreasing Fe2+/Fe3+ ratios. This style of alteration is referred to as rock-dominated serpentinization. In contrast, fluid-dominated serpentinization at Site 1268 is characterized by gains in sulfur and development of U-shaped REE pattern with strong positive Eu anomalies which are also characteristic for hot (350 to 400°C) vent-type fluids discharging from black smoker fields. Serpentinites at Site 1268 were overprinted by talc alteration under static conditions due to interaction with high aSiO2 fluids causing the development of smooth, LREE-enriched patterns with pronounced negative Eu anomalies. These results show that hydrothermal fluid-peridotite and fluid-serpentinite interaction processes are an important factor regarding the budget of exchange processes between the lithosphere and the hydrosphere in slow spreading environments.ODP is sponsored by the U.S. National Science Foundation (NSF) and participating countries under management of Joint Oceanographic Institutions (JOI), Inc

Compositional variation and 226Ra-230Th model ages of axial lavas from the southern Mid-Atlantic Ridge, 8°48′S

We present geological observations and geochemical data for the youngest volcanic features on the slow-spreading Mid-Atlantic Ridge at 8°48'S that shows seismic evidence for a thickened crust and excess magma formation. Young lava flows with high sonar reflectivity cover about 14 km2 in the axial rift and were probably erupted from two axial volcanic ridges each of about 3 km in length. Three different lava units occur along an about 11 km long portion of the ridge, and lavas from the northern axial volcanic ridge differ from those of the southern axial volcanic ridge and surrounding lava flows. Basalts from the axial rift flanks and from a pillow mound within the young flows are more incompatible element depleted than those from the young volcanic field. Lavas from this volcanic area have 226Ra-230Th disequilibria model ages of 1,000 and 4,000 years whereas the older lavas from the rift flank and the pillow mound, but also some of the lava field, are older than 8,000 years. Glasses from the northern and southern ends of the southern lava unit indicate up to 100°C cooler magma temperatures than in the center and increased assimilation of hydrothermally altered material. The compositional heterogeneity on a scale of 3 km suggests small magma batches rising vertically from the mantle to the surface without significant lateral flow and mixing. The observations on the 8°48'S lava field support the model of low frequency eruptions from single ascending magma batches that has been developed for slow-spreading ridges

Transcript Expression Analysis of Putative Trypanosoma brucei GPI-Anchored Surface Proteins during Development in the Tsetse and Mammalian Hosts

Human African Trypanosomiasis is a devastating disease caused by the parasite Trypanosoma brucei. Trypanosomes live extracellularly in both the tsetse fly and the mammal. Trypanosome surface proteins can directly interact with the host environment, allowing parasites to effectively establish and maintain infections. Glycosylphosphatidylinositol (GPI) anchoring is a common posttranslational modification associated with eukaryotic surface proteins. In T. brucei, three GPI-anchored major surface proteins have been identified: variant surface glycoproteins (VSGs), procyclic acidic repetitive protein (PARP or procyclins), and brucei alanine rich proteins (BARP). The objective of this study was to select genes encoding predicted GPI-anchored proteins with unknown function(s) from the T. brucei genome and characterize the expression profile of a subset during cyclical development in the tsetse and mammalian hosts. An initial in silico screen of putative T. brucei proteins by Big PI algorithm identified 163 predicted GPI-anchored proteins, 106 of which had no known functions. Application of a second GPI-anchor prediction algorithm (FragAnchor), signal peptide and trans-membrane domain prediction software resulted in the identification of 25 putative hypothetical proteins. Eighty-one gene products with hypothetical functions were analyzed for stage-regulated expression using semi-quantitative RT-PCR. The expression of most of these genes were found to be upregulated in trypanosomes infecting tsetse salivary gland and proventriculus tissues, and 38% were specifically expressed only by parasites infecting salivary gland tissues. Transcripts for all of the genes specifically expressed in salivary glands were also detected in mammalian infective metacyclic trypomastigotes, suggesting a possible role for these putative proteins in invasion and/or establishment processes in the mammalian host. These results represent the first large-scale report of the differential expression of unknown genes encoding predicted T. brucei surface proteins during the complete developmental cycle. This knowledge may form the foundation for the development of future novel transmission blocking strategies against metacyclic parasites

N-Glycans and Glycosylphosphatidylinositol-Anchor Act on Polarized Sorting of Mouse PrPC in Madin-Darby Canine Kidney Cells

The cellular prion protein (PrPC) plays a fundamental role in prion disease. PrPC is a glycosylphosphatidylinositol (GPI)-anchored protein with two variably occupied N-glycosylation sites. In general, GPI-anchor and N-glycosylation direct proteins to apical membranes in polarized cells whereas the majority of mouse PrPC is found in basolateral membranes in polarized Madin-Darby canine kidney (MDCK) cells. In this study we have mutated the first, the second, and both N-glycosylation sites of PrPC and also replaced the GPI-anchor of PrPC by the Thy-1 GPI-anchor in order to investigate the role of these signals in sorting of PrPC in MDCK cells. Cell surface biotinylation experiments and confocal microscopy showed that lack of one N-linked oligosaccharide leads to loss of polarized sorting of PrPC. Exchange of the PrPC GPI-anchor for the one of Thy-1 redirects PrPC to the apical membrane. In conclusion, both N-glycosylation and GPI-anchor act on polarized sorting of PrPC, with the GPI-anchor being dominant over N-glycans