Microscale Flow Modeling in Geologic Materials

Three-dimensional imaging techniques, numerical methods for simulating flow and transport, and emergent computational architectures are combined to enable fundamental studies of fluid flow at the pore scale. High resolution reconstructions of porous media obtained using laser scanning confocal microscopy reduce sampling artifacts to sub-micron features, and simultaneously capture multiple grain length scales. However, the volumetric image data sets are extremely large, and there are significant computational challenges in utilizing this information effectively. The principal problem lies in the complexity of the geometry and the retention of this structure in numerical analyses. Lattice Boltzmann (LB) methods provide a direct means to simulate transport processes in complex geometric domains due to the unique ability to treat accurately and efficiently the multitude of discrete boundary conditions. LB methods are numerically explicit as formulated, and this characteristic is exploited through a mapping of the numerical domain to distributed computing architectures. These techniques are applied to perform single phase flow simulations in 3D data sets obtained from cores of Berea sandstone using confocal microscopy. Simulations are performed using both a purpose-built distributed processor computer and a massively parallel processer (MPP) platform

Aldosterone signaling through transient receptor potential melastatin 7 cation channel (TRPM7) and its α-kinase domain

We demonstrated a role for the Mg2 + transporter TRPM7, a bifunctional protein with channel and α-kinase domains, in aldosterone signaling. Molecular mechanisms underlying this are elusive. Here we investigated the function of TRPM7 and its α-kinase domain on Mg2 + and pro-inflammatory signaling by aldosterone. Kidney cells (HEK-293) expressing wild-type human TRPM7 (WThTRPM7) or constructs in which the α-kinase domain was deleted (ΔKinase) or rendered inactive with a point mutation in the ATP binding site of the α-kinase domain (K1648R) were studied. Aldosterone rapidly increased [Mg2 +]i and stimulated NADPH oxidase-derived generation of reactive oxygen species (ROS) in WT hTRPM7 and TRPM7 kinase dead mutant cells. Translocation of annexin-1 and calpain-II and spectrin cleavage (calpain target) were increased by aldosterone in WT hTRPM7 cells but not in α-kinase-deficient cells. Aldosterone stimulated phosphorylation of MAP kinases and increased expression of pro-inflammatory mediators ICAM-1, Cox-2 and PAI-1 in Δkinase and K1648R cells, effects that were inhibited by eplerenone (mineralocorticoid receptor (MR) blocker). 2-APB, a TRPM7 channel inhibitor, abrogated aldosterone-induced Mg2 + responses in WT hTRPM7 and mutant cells. In 2-APB-treated ΔKinase and K1648R cells, aldosterone-stimulated inflammatory responses were unchanged. These data indicate that aldosterone stimulates Mg2 + influx and ROS production in a TRPM7-sensitive, kinase-insensitive manner, whereas activation of annexin-1 requires the TRPM7 kinase domain. Moreover TRPM7 α-kinase modulates inflammatory signaling by aldosterone in a TRPM7 channel/Mg2 +-independent manner. Our findings identify novel mechanisms for non-genomic actions of aldosterone involving differential signaling through MR-activated TRPM7 channel and α-kinase

Sources and mixing state of size-resolved elemental carbon particles in a European megacity: Paris

An Aerosol Time-Of-Flight Mass Spectrometer (ATOFMS) was deployed to investigate the size-resolved chemical composition of single particles at an urban background site in Paris, France, as part of the MEGAPOLI winter campaign in January/February 2010. ATOFMS particle counts were scaled to match coincident Twin Differential Mobility Particle Sizer (TDMPS) data in order to generate hourly size-resolved mass concentrations for the single particle classes observed. The total scaled ATOFMS particle mass concentration in the size range 150–1067 nm was found to agree very well with the sum of concurrent High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) and Multi-Angle Absorption Photometer (MAAP) mass concentration measurements of organic carbon (OC), inorganic ions and black carbon (BC) (R2 = 0.91). Clustering analysis of the ATOFMS single particle mass spectra allowed the separation of elemental carbon (EC) particles into four classes: (i) EC attributed to biomass burning (ECbiomass), (ii) EC attributed to traffic (ECtraffic), (iii) EC internally mixed with OC and ammonium sulfate (ECOCSOx), and (iv) EC internally mixed with OC and ammonium nitrate (ECOCNOx). Average hourly mass concentrations for EC-containing particles detected by the ATOFMS were found to agree reasonably well with semi-continuous quantitative thermal/optical EC and optical BC measurements (r2 = 0.61 and 0.65–0.68 respectively, n = 552). The EC particle mass assigned to fossil fuel and biomass burning sources also agreed reasonably well with BC mass fractions assigned to the same sources using seven-wavelength aethalometer data (r2 = 0.60 and 0.48, respectively, n = 568). Agreement between the ATOFMS and other instrumentation improved noticeably when a period influenced by significantly aged, internally mixed EC particles was removed from the intercomparison. 88% and 12% of EC particle mass was apportioned to fossil fuel and biomass burning respectively using the ATOFMS data compared with 85% and 15% respectively for BC estimated from the aethalometer model. On average, the mass size distribution for EC particles is bimodal; the smaller mode is attributed to locally emitted, mostly externally mixed EC particles, while the larger mode is dominated by aged, internally mixed ECOCNOx particles associated with continental transport events. Periods of continental influence were identified using the Lagrangian Particle Dispersion Model (LPDM) "FLEXPART". A consistent minimum between the two EC mass size modes was observed at approximately 400 nm for the measurement period. EC particles below this size are attributed to local emissions using chemical mixing state information and contribute 79% of the scaled ATOFMS EC particle mass, while particles above this size are attributed to continental transport events and contribute 21% of the EC particle mass. These results clearly demonstrate the potential benefit of monitoring size-resolved mass concentrations for the separation of local and continental EC emissions. Knowledge of the relative input of these emissions is essential for assessing the effectiveness of local abatement strategies

Quantitative determination of carbonaceous particle mixing state in Paris using single-particle mass spectrometer and aerosol mass spectrometer measurements

Single-particle mixing state information can be a powerful tool for assessing the relative impact of local and regional sources of ambient particulate matter in urban environments. However, quantitative mixing state data are challenging to obtain using single-particle mass spectrometers. In this study, the quantitative chemical composition of carbonaceous single particles has been determined using an aerosol time-of-flight mass spectrometer (ATOFMS) as part of the MEGAPOLI 2010 winter campaign in Paris, France. Relative peak areas of marker ions for elemental carbon (EC), organic aerosol (OA), ammonium, nitrate, sulfate and potassium were compared with concurrent measurements from an Aerodyne high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS), a thermal–optical OCEC analyser and a particle into liquid sampler coupled with ion chromatography (PILS-IC). ATOFMS-derived estimated mass concentrations reproduced the variability of these species well (R2 = 0.67–0.78), and 10 discrete mixing states for carbonaceous particles were identified and quantified. The chemical mixing state of HR-ToF-AMS organic aerosol factors, resolved using positive matrix factorisation, was also investigated through comparison with the ATOFMS dataset. The results indicate that hydrocarbon-like OA (HOA) detected in Paris is associated with two EC-rich mixing states which differ in their relative sulfate content, while fresh biomass burning OA (BBOA) is associated with two mixing states which differ significantly in their OA / EC ratios. Aged biomass burning OA (OOA2-BBOA) was found to be significantly internally mixed with nitrate, while secondary, oxidised OA (OOA) was associated with five particle mixing states, each exhibiting different relative secondary inorganic ion content. Externally mixed secondary organic aerosol was not observed. These findings demonstrate the range of primary and secondary organic aerosol mixing states in Paris. Examination of the temporal behaviour and chemical composition of the ATOFMS classes also enabled estimation of the relative contribution of transported emissions of each chemical species and total particle mass in the size range investigated. Only 22% of the total ATOFMS-derived particle mass was apportioned to fresh, local emissions, with 78% apportioned to regional/continental-scale emissions

Mechanisms underlying a thalamocortical transformation during active tactile sensation

During active somatosensation, neural signals expected from movement of the sensors are suppressed in the cortex, whereas information related to touch is enhanced. This tactile suppression underlies low-noise encoding of relevant tactile features and the brain’s ability to make fine tactile discriminations. Layer (L) 4 excitatory neurons in the barrel cortex, the major target of the somatosensory thalamus (VPM), respond to touch, but have low spike rates and low sensitivity to the movement of whiskers. Most neurons in VPM respond to touch and also show an increase in spike rate with whisker movement. Therefore, signals related to self-movement are suppressed in L4. Fast-spiking (FS) interneurons in L4 show similar dynamics to VPM neurons. Stimulation of halorhodopsin in FS interneurons causes a reduction in FS neuron activity and an increase in L4 excitatory neuron activity. This decrease of activity of L4 FS neurons contradicts the "paradoxical effect" predicted in networks stabilized by inhibition and in strongly-coupled networks. To explain these observations, we constructed a model of the L4 circuit, with connectivity constrained by in vitro measurements. The model explores the various synaptic conductance strengths for which L4 FS neurons actively suppress baseline and movement-related activity in layer 4 excitatory neurons. Feedforward inhibition, in concert with recurrent intracortical circuitry, produces tactile suppression. Synaptic delays in feedforward inhibition allow transmission of temporally brief volleys of activity associated with touch. Our model provides a mechanistic explanation of a behavior-related computation implemented by the thalamocortical circuit

Spallation reactions. A successful interplay between modeling and applications

The spallation reactions are a type of nuclear reaction which occur in space by interaction of the cosmic rays with interstellar bodies. The first spallation reactions induced with an accelerator took place in 1947 at the Berkeley cyclotron (University of California) with 200 MeV deuterons and 400 MeV alpha beams. They highlighted the multiple emission of neutrons and charged particles and the production of a large number of residual nuclei far different from the target nuclei. The same year R. Serber describes the reaction in two steps: a first and fast one with high-energy particle emission leading to an excited remnant nucleus, and a second one, much slower, the de-excitation of the remnant. In 2010 IAEA organized a worskhop to present the results of the most widely used spallation codes within a benchmark of spallation models. If one of the goals was to understand the deficiencies, if any, in each code, one remarkable outcome points out the overall high-quality level of some models and so the great improvements achieved since Serber. Particle transport codes can then rely on such spallation models to treat the reactions between a light particle and an atomic nucleus with energies spanning from few tens of MeV up to some GeV. An overview of the spallation reactions modeling is presented in order to point out the incomparable contribution of models based on basic physics to numerous applications where such reactions occur. Validations or benchmarks, which are necessary steps in the improvement process, are also addressed, as well as the potential future domains of development. Spallation reactions modeling is a representative case of continuous studies aiming at understanding a reaction mechanism and which end up in a powerful tool.Comment: 59 pages, 54 figures, Revie

Implementing subtype-specific pre-clinical models of breast cancer to study pre-treatment aspirin effects

YesBackgorund Prior data suggest pre-diagnostic aspirin use impacts breast tumour biology and patient outcome. Here, we employed faithful surgical resection models of HER2+ and triple-negative breast cancer (TNBC), to study outcome and response mechanisms across breast cancer subtypes. Method NOD/SCID mice were implanted with HER2+ MDA-MB-231/LN/2-4/H2N, trastuzumab-resistant HER2+ HCC1954 or a TNBC patient-derived xenograft (PDX). A daily low-dose aspirin regimen commenced until primary tumours reached ~250 mm3 and subsequently resected. MDA-MB-231/LN/2-4/H2N mice were monitored for metastasis utilising imaging. To interrogate the survival benefit of pre-treatment aspirin, 3 weeks post-resection, HCC1954/TNBC animals received standard-of-care (SOC) chemotherapy for 6 weeks. Primary tumour response to aspirin was interrogated using immunohistochemistry. Results Aspirin delayed time to metastasis in MDA-MB-231/LN/2-4/H2N xenografts and decreased growth of HER2+/TNBC primary tumours. Lymphangiogenic factors and lymph vessels number were decreased in HER2+ tumours. However, no survival benefit was seen in aspirin pre-treated animals (HCC1954/TNBC) that further received adjuvant SOC, compared with animals treated with SOC alone. In an effort to study mechanisms responsible for the observed reduction in lymphangiogenesis in HER2+ BC we utilised an in vitro co-culture system of HCC1954 tumour cells and mesenchymal stromal cells (MSC). Aspirin abrogated the secretion of VEGF-C in MSCs and also decreased the lymph/angiogenic potential of the MSCs and HCC1954 by tubule formation assay. Furthermore, aspirin decreased the secretion of uPA in HCC1954 cells potentially diminishing its metastatic capability. Conclusion Our data employing clinically relevant models demonstrate that aspirin alters breast tumour biology. However, aspirin may not represent a robust chemo-preventative agent in the HER2+ or TNBC setting.Funding is acknowledged from the Irish Cancer Society Collaborative Cancer Research Centre under BREAST- PREDICT grant CCRC13GAL (www.breas tpred ict.com). I.S.M, E.M and A.T.B, are members of the EurOPDX Consortium, and receive funding from the European Union's Horizon 2020 research and innovation programme, grant agreement no. #731105 (EurOPDX Research Infrastructure, www.europ dx.eu)

Integrated motor drives: state of the art and future trends

With increased need for high power density, high efficiency and high temperature capabilities in Aerospace and Automotive applications, Integrated Motor Drives (IMD) offers a potential solution. However, close physical integration of the converter and the machine may also lead to an increase in components temperature. This requires careful mechanical, structural and thermal analysis; and design of the IMD system. This paper reviews existing IMD technologies and their thermal effects on the IMD system. The effects of the power electronics (PE) position on the IMD system and its respective thermal management concepts are also investigated. The challenges faced in designing and manufacturing of an IMD along with the mechanical and structural impacts of close physical integration is also discussed and potential solutions are provided. Potential converter topologies for an IMD like the Matrix converter, 2-level Bridge, 3-level NPC and Multiphase full bridge converters are also reviewed. Wide band gap devices like SiC and GaN and their packaging in power modules for IMDs are also discussed. Power modules components and packaging technologies are also presented