A Practical Approach for Wall Shear Stress Topological Skeleton Analysis Applied to Intracranial Aneurysm Hemodynamics

The physiopathological role of Wall Shear Stress (WSS) in intracranial aneurysm development/rupture and the action of contraction/expansion played by shear forces on vessel wall make topological skeleton analysis of the WSS vector field of great interest. Here we present a practical way to analyze WSS topological skeleton through the identification and classification of WSS fixed points and manifolds. The method is based on the calculation of the WSS vector field divergence and Poincarè index, and it is here successfully applied to a dataset computational hemodynamic models of intracranial aneurysms

Exploring novel arterio-venous graft designs to reduce vascular access failure risk

Although arterio-venous grafts (AVGs) are the second best option as permanent vascular access for hemodialysis, this solution is still affected by a relevant failure rate associated with neointimal hyperplasia (IH), mainly located at the venous anastomosis, where abnormal hemodynamics occurs. In this study we use computational fluid dynamics (CFD) to investigate the impact of six innovative AVG designs on reducing the IH risk at the distal anastomosis in AVGs. Findings from simulations clearly show that using a helical shaped flow divider located in the venous side of the graft could assure a reduced hemodynamic risk of failure at the distal anastomosis, with a clinically irrelevant increase in pressure drop over the graft

LARGE Volume String Compactifications at Finite Temperature

We present a detailed study of the finite-temperature behaviour of the LARGE Volume type IIB flux compactifications. We show that certain moduli can thermalise at high temperatures. Despite that, their contribution to the finite-temperature effective potential is always negligible and the latter has a runaway behaviour. We compute the maximal temperature $T_{max}$, above which the internal space decompactifies, as well as the temperature $T_*$, that is reached after the decay of the heaviest moduli. The natural constraint $T_*<T_{max}$ implies a lower bound on the allowed values of the internal volume $\mathcal{V}$. We find that this restriction rules out a significant range of values corresponding to smaller volumes of the order $\mathcal{V}\sim 10^{4}l_s^6$, which lead to standard GUT theories. Instead, the bound favours values of the order $\mathcal{V}\sim 10^{15}l_s^6$, which lead to TeV scale SUSY desirable for solving the hierarchy problem. Moreover, our result favours low-energy inflationary scenarios with density perturbations generated by a field, which is not the inflaton. In such a scenario, one could achieve both inflation and TeV-scale SUSY, although gravity waves would not be observable. Finally, we pose a two-fold challenge for the solution of the cosmological moduli problem. First, we show that the heavy moduli decay before they can begin to dominate the energy density of the Universe. Hence they are not able to dilute any unwanted relics. And second, we argue that, in order to obtain thermal inflation in the closed string moduli sector, one needs to go beyond the present EFT description.Comment: 54 pages + appendix, 5 figures; v2: minor corrections, references and footnotes added, version published on JCA

Non Abelian Geometrical Tachyon

We investigate the dynamics of a pair of coincident D5 branes in the background of $k$ NS5 branes. It has been proposed by Kutasov that the system with a single probing D-brane moving radially in this background is dual to the tachyonic DBI action for a non-BPS Dp brane. We extend this proposal to the non-abelian case and find that the duality still holds provided one promotes the radial direction to a matrix valued field associated with a non-abelian geometric tachyon and a particular parametrization for the transverse scalar fields is chosen. The equations of motion of a pair of coincident D5 branes moving in the NS5 background are determined. Analytic and numerical solutions for the pair are found in certain simplified cases in which the U(2) symmetry is broken to $U(1) \times U(1)$ corresponding to a small transverse separation of the pair. For certain range of parameters these solutions describe periodic motion of the centre of mass of the pair 'bouncing off' a finite sized throat whose minimum size is limited by the D5 branes separation.Comment: 18 pages, 2 figures, PdfLatex: references added.accepted for publication in JHE

BRCA1/BRCA2 rearrangements and CHEK2 common mutations are infrequent in Italian male breast cancer cases.

Male breast cancer (MBC) is a rare and poorly known disease. Germ-line mutations of BRCA2 and, to lesser extent, BRCA1 genes are the highest risk factors associated with MBC. Interestingly, BRCA2 germ-line rearrangements have been described in high-risk breast/ovarian cancer families which included at least one MBC case. Germ-line mutations of CHEK2 gene have been also implicated in inherited MBC predisposition. The CHEK2 1100delC mutation has been shown to increase the risk of breast cancer in men lacking BRCA1/BRCA2 mutations. Intriguingly, two other CHEK2 mutations (IVS2+1G > A and I157T) and a CHEK2 large genomic deletion (del9-10) have been associated with an elevated risk for prostate cancer. Here, we investigated the contribution of BRCA1, BRCA2 and CHEK2 alterations to MBC predisposition in Italy by analysing a large series of MBC cases, unselected for breast cancer family history and all negative for BRCA1/BRCA2 germ-line mutations. A total of 102 unrelated Italian MBC cases were screened for deletions/duplications of BRCA1, BRCA2 and CHEK2 by multiplex ligation-dependent probe amplification. No BRCA1, BRCA2 and CHEK2 genomic rearrangements, including the CHEK2 del9-10, were found in the series analysed. Furthermore, none of the MBC cases and 263 male population controls, also included in this study, carried the CHEK2 1100delC, IVS2+1G > A and I157T common mutations. Overall, our data suggest that screening of BRCA1/2 rearrangements is not advantageous in MBC cases not belonging to high-risk breast cancer families and that common CHEK2 mutations play an irrelevant role in MBC predisposition in Italy

Clones Identification and Genetic Characterization of Garnacha Grapevine by Means of Different PCR-Derived Marker Systems

This study uses PCR-derived marker systems to investigate the extent and distribution of genetic variability of 53 Garnacha accessions coming from Italy, France and Spain. The samples studied include 28 Italian accessions (named Tocai rosso in Vicenza area; Alicante in Sicily and Elba island; Gamay perugino in Perugia province; Cannonau in Sardinia), 19 Spanish accessions of different types (named Garnacha tinta, Garnacha blanca, Garnacha peluda, Garnacha roja, Garnacha erguida, Garnacha roya) and 6 French accessions (named Grenache and Grenache noir). In order to verify the varietal identity of the samples, analyses based on 14 simple sequence repeat (SSR) loci were performed. The presence of an additional allele at ISV3 locus (151 bp) was found in four Tocai rosso accessions and in a Sardinian Cannonau clone, that are, incidentally, chimeras. In addition to microsatellite analysis, intravarietal variability study was performed using AFLP, SAMPL and M-AFLP molecular markers. AFLPs could discriminate among several Garnacha samples; SAMPLs allowed distinguishing few genotypes on the basis of their geographic origin, whereas M-AFLPs revealed plant-specific markers, differentiating all accessions. Italian samples showed the greatest variability among themselves, especially on the basis of their different provenance, while Spanish samples were the most similar, in spite of their morphological diversity

Non Abelian Tachyon Kinks

Starting from the action of two coincident non-BPS D9-branes, we investigate kink configurations of the U(2) matrix tachyon field. We consider both Str and Tr prescriptions for the trace over gauge indices of the non-BPS action. Non-abelian tachyon condensation in the theory with Tr prescription, and the resulting fluctuations about the kink profile, are shown to give rise to a theory of two coincident BPS D8-branes. This is a natural non-abelian generalization of Sen's mechanism of tachyon condensation on a single non-BPS Dp-brane yielding a single BPS brane of codimesion one. By contrast, starting with the Str gauge trace prescription of the coincident non-BPS D9-brane action, such a generalization of Sen's mechanism appears problematic.Comment: 18 pages, references added, version to appear in JHE

Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction

The nociceptin (NOP) receptor is a G-protein-coupled receptor whose natural ligand is the nociceptin/orphanin FQ (N/OFQ) peptide. Evidence from pharmacological studies suggests that the N/OFQ system is implicated in the regulation of several addiction-related phenomena, such as drug intake, withdrawal and relapse. Here, to further explore the role of NOP system in addiction, we used NOP (-/-) rats to study the motivation for cocaine, heroin and alcohol self-administration in the absence of N/OFQ function. Conditioned place preference (CPP) and saccharin (0.2% w/v) self-administration were also investigated. Results showed that NOP (-/-) rats self-administer less cocaine (0.25, 0.125 or 0.5 mg/infusion) both under a Fixed Ratio 1 and a Progressive Ratio schedule of reinforcement compared to wild type (Wt) controls. Consistently, cocaine (10 mg/kg, i.p.) was able to induce CPP in Wt but not in NOP (-/-). When NOP (-/-) rats were tested for heroin (20 μg/infusion) and ethanol (10% v/v) self-administration, they showeda significantly lower drug intake compared to Wt. Conversely, saccharin self-administration was not affected by NOP deletion, excluding the possibility of nonspecific learning deficits or generalized disruption of reward mechanisms in NOP (-/-) rats. These findings were confirmed with pharmacological experiments using two selective NOP antagonists, SB-612111 and LY2817412. Both drugs attenuated alcohol self-administration in Wt rats but not in NOP (-/-) rats. In conclusion, our results demonstrate that genetic deletion of NOP receptors confers resilience to drug abuse and support a role for NOP receptor antagonism as a potential treatment option for drug addiction.Neuropsychopharmacology accepted article preview online, 26 August 2016. doi:10.1038/npp.2016.171

Carbon Monoxide Induced Erythroid Differentiation of K562 Cells Mimics the Central Macrophage Milieu in Erythroblastic Islands

Growing evidence supports the role of erythroblastic islands (EI) as microenvironmental niches within bone marrow (BM), where cell-cell attachments are suggested as crucial for erythroid maturation. The inducible form of the enzyme heme oxygenase, HO-1, which conducts heme degradation, is absent in erythroblasts where hemoglobin (Hb) is synthesized. Yet, the central macrophage, which retains high HO-1 activity, might be suitable to take over degradation of extra, harmful, Hb heme. Of these enzymatic products, only the hydrophobic gas molecule - CO can transfer from the macrophage to surrounding erythroblasts directly via their tightly attached membranes in the terminal differentiation stage