Robust preconditioners for a new stabilized discretization of the poroelastic equations

In this paper, we present block preconditioners for a stabilized discretization of the poroelastic equations developed in [45]. The discretization is proved to be well-posed with respect to the physical and discretization parameters, and thus provides a framework to develop preconditioners that are robust with respect to such parameters as well. We construct both norm-equivalent (diagonal) and field-of-value-equivalent (triangular) preconditioners for both the stabilized discretization and a perturbation of the stabilized discretization that leads to a smaller overall problem after static condensation. Numerical tests for both two- and three-dimensional problems confirm the robustness of the block preconditioners with respect to the physical and discretization parameters

Management of anticoagulant-refractory thrombotic antiphospholipid syndrome

Lifelong anticoagulation with warfarin or alternative vitamin K antagonist is the standard anticoagulant treatment for thrombotic antiphospholipid syndrome. Anticoagulant-refractory thrombotic antiphospholipid syndrome can be broadly defined as breakthrough thrombosis while on standard oral anticoagulation treatment and its management is a major challenge given the serious nature of the thrombotic disease observed, which has become refractory to oral anticoagulation. The factors (genetic and cellular) that cause anticoagulant-refractory thrombotic antiphospholipid syndrome are now better understood. However, efforts to use this greater understanding have not yet transformed the capacity to treat it successfully in many patients. In this Viewpoint, we review the factors that are likely to be contributing to the cause of this syndrome and consider how they might be modified or inhibited. We also discuss management, including general strategies to minimise thrombotic risk, intensification of anticoagulation, addition of an antiplatelet agent, adjunctive treatment for thrombosis, immunomodulatory therapy, complement inhibition, vascular options, and future potential therapeutic targets

Protoplanetary and Transitional Disks in the Open Stellar Cluster IC 2395

We present new deep UBVRI images and high-resolution multi-object optical spectroscopy of the young (~ 6 - 10 Myr old), relatively nearby (800 pc) open cluster IC 2395. We identify nearly 300 cluster members and use the photometry to estimate their spectral types, which extend from early B to middle M. We also present an infrared imaging survey of the central region using the IRAC and MIPS instruments on board the Spitzer Space Telescope, covering the wavelength range from 3.6 to 24 microns. Our infrared observations allow us to detect dust in circumstellar disks originating over a typical range of radii ~ 0.1 to ~ 10AU from the central star. We identify 18 Class II, 8 transitional disk, and 23 debris disk candidates, respectively 6.5%, 2.9%, and 8.3% of the cluster members with appropriate data. We apply the same criteria for transitional disk identification to 19 other stellar clusters and associations spanning ages from ~ 1 to ~ 18 Myr. We find that the number of disks in the transitional phase as a fraction of the total with strong 24 micron excesses ([8] - [24] > 1.5) increases from 8.4 +\- 1.3% at ~ 3 Myr to 46 +\- 5% at ~ 10 Myr. Alternative definitions of transitional disks will yield different percentages but should show the same trend.Comment: accepted by the Astrophysical Journa

Metabolite and thymocyte development defects in ADA-SCID mice receiving enzyme replacement therapy

Deficiency of adenosine deaminase (ADA, EC3.5.4.4), a housekeeping enzyme intrinsic to the purine salvage pathway, leads to severe combined immunodeficiency (SCID) both in humans and mice. Lack of ADA results in the intracellular accumulation of toxic metabolites which have effects on T cell development and function. While untreated ADA-SCID is a fatal disorder, there are different therapeutic options available to restore ADA activity and reconstitute a functioning immune system, including enzyme replacement therapy (ERT). Administration of ERT in the form of pegylated bovine ADA (PEG-ADA) has proved a life-saving though non-curative treatment for ADA-SCID patients. However, in many patients treated with PEG-ADA, there is suboptimal immune recovery with low T and B cell numbers. Here, we show reduced thymus cellularity in ADA-SCID mice despite weekly PEG-ADA treatment. This was associated with lack of effective adenosine (Ado) detoxification in the thymus. We also show that thymocyte development in ADA-deficient thymi is arrested at the DN3-to-DN4 stage transition with thymocytes undergoing dATP-induced apoptosis rather than defective TCRβ rearrangement or β-selection. Our studies demonstrate at a detailed level that exogenous once-a-week enzyme replacement does not fully correct intra-thymic metabolic or immunological abnormalities associated with ADA deficiency

A genome-wide association study using a DNA pooling strategy identifies BBS9 and GLIS3 as novel loci influencing patient’s outcome after stroke

Stroke is a major cause of morbidity in developed countries and therefore finding adequate treatments to promote patient’s recovery is a priority task, requiring the elucidation of the molecular pathways influencing brain recovery. Few studies, however, have assessed the role of genes in stroke outcome. This study describes a pilot genome-wide association study (GWAS) to identify genetic factors contributing to patient’s outcome, using a DNA pooling design. Methods: Patient’s outcome was assessed using the modified Rankin Scale (mRS) three months after stroke. Using the 250K Affymetrix GeneChip Mapping Assay® – Nsp I, we compared SNP allele frequencies in a pool of non-disabled stroke patients (N=87, mRS=0), with a pool of severely disabled or deceased patients (N=100, mRS>=3). The 100 most interesting SNPs were selected for validation by individual genotyping. Results: 36 SNPs were validated, showing significant differences between patients with extremely good and extremely poor outcome at three months (1.7x10-4 ).This work was supported by the grant PTDC/SAU-GMG/64426/2006, Fundação para a Ciência e Tecnologia (FCT). Helena Manso and Tiago Krug were supported by FCT fellowships

A Step Forward in Breast Cancer Research: Gold Nanoparticles as Photothermal Therapy Enhancers

Gold nanoparticles (AuNPs) have been widely used and characterized for multiple biomedical applications, including the enhancement of photothermal therapy (PTT). AuNPs present a particular plasmon resonance band and are able to convert the absorbed optical radiation into heat, which validates their use in PTT. Several production methods have already been proposed for the synthesis of AuNPs, allowing to optimize the particles' morphology, size and optical properties. However, the production methods commonly used are frequently associated with the use of toxic reagents such as Cetyltrimethylammonium bromide, which presents some concerns for clinical applications. Herein, it is proposed a novel AuNPs' core synthesis method using tetrachloroauric acid and a mixture of reducing agents, later on coated with a combination of hyaluronic and oleic acids. The coating here represents a potential improvement of AuNPs biocompatibility, biodegradability and lifetime, while simultaneously potentiating the attachment towards specific ligands, such as the CD44 receptor, to develop more localized and highly selective tools. The produced functionalized nanoparticles were characterized by Dynamic Light Scattering, Microscopy Techniques and Spectroscopy, showing diameter sizes under 350 nm, polydispersity index smaller than 0.4 and enhanced absorbance in the Near Infrared (NIR, 650 to 900 nm) range. Moreover, the AuNPs safety and efficacy were preliminarily assessed in vitro using breast cancer cell lines. No toxicity was observed by MTT assay, both in breast cancer cell lines, and red blood cells. The irradiation process was proved to be safe; however, when combined with the AuNPs administration, it resulted in a significant reduction of cell viability for some of the breast cell lines tested. Thus, the results highlight the potential of the proposed system for some type of tumors, even though further tests are required to better understand the mechanisms behind the obtained results

Producing Foils From Direct Cast Titanium Alloy Strip

This research was undertaken to demonstrate the feasibility of producing high-quality, thin-gage, titanium foil from direct cast titanium strip. Melt Overflow Rapid Solidification Technology (MORST) was used to cast several different titanium alloys into 500 microns thick strip, 10 cm wide and up to 3 m long. The strip was then either ground, hot pack rolled or cold rolled, as appropriate, into foil. Gamma titanium aluminide (TiAl) was cast and ground to approximately 100 microns thick foil and alpha-2 titanium aluminide (Ti3AI) was cast and hot pack rolled to approximately 70 microns thick foil. CP Ti, Ti6Al2Sn4Zr2Mo, and Ti22AI23Nb (Orthorhombic), were successfully cast and cold-rolled into good quality foil (less than 125 microns thick). The foils were generally fully dense with smooth surfaces, had fine, uniform microstructures, and demonstrated mechanical properties equivalent to conventionally produced titanium. By eliminating many manufacturing steps, this technology has the potential to produce thin gage, titanium foil with good engineering properties at significantly reduced cost relative to conventional ingot metallurgy processing