Atherosusceptible Shear Stress Activates Endoplasmic Reticulum Stress to Promote Endothelial Inflammation.

Atherosclerosis impacts arteries where disturbed blood flow renders the endothelium susceptible to inflammation. Cytokine activation of endothelial cells (EC) upregulates VCAM-1 receptors that target monocyte recruitment to atherosusceptible regions. Endoplasmic reticulum (ER) stress elicits EC dysregulation in metabolic syndrome. We hypothesized that ER plays a central role in mechanosensing of atherosusceptible shear stress (SS) by signaling enhanced inflammation. Aortic EC were stimulated with low-dose TNFα (0.3 ng/ml) in a microfluidic channel that produced a linear SS gradient over a 20mm field ranging from 0-16 dynes/cm2. High-resolution imaging of immunofluorescence along the monolayer provided a continuous spatial metric of EC orientation, markers of ER stress, VCAM-1 and ICAM-1 expression, and monocyte recruitment. VCAM-1 peaked at 2 dynes/cm2 and decreased to below static TNFα-stimulated levels at atheroprotective-SS of 12 dynes/cm2, whereas ICAM-1 rose to a maximum in parallel with SS. ER expansion and activation of the unfolded protein response also peaked at 2 dynes/cm2, where IRF-1-regulated VCAM-1 expression and monocyte recruitment also rose to a maximum. Silencing of PECAM-1 or key ER stress genes abrogated SS regulation of VCAM-1 transcription and monocyte recruitment. We report a novel role for ER stress in mechanoregulation at arterial regions of atherosusceptible-SS inflamed by low-dose TNFα

A dual output polarimeter devoted to the study of the Cosmic Microwave Background

We have developed a correlation radiometer at 33 GHz devoted to the search for residual polarization of the Cosmic Microwave Background (CMB). The two instruments`s outputs are linear combination of two Stokes Parameters (Q and U or U and V). The instrument is therefore directly sensitive to the polarized component of the radiation (respectively linear and circular). The radiometer has a beam-width oif 7 or 14 deg, but it can be coupled to a telescope increasing the resolution. The expected CMB polarization is at most a part per milion. The polarimeter has been designed to be sensitive to this faint signal, and it has been optimized to improve its long term stability, observing from the ground. In this contribution the performances of the instrument are presented, together with the preliminary test and observations.Comment: 12 pages, 6 figures, in print on the Proc. SPIE Conf. - August 200

A note on the integral equation for the Wilson loop in N = 2 D=4 superconformal Yang-Mills theory

We propose an alternative method to study the saddle point equation in the strong coupling limit for the Wilson loop in $\mathcal{N}=2$ D=4 super Yang-Mills with an SU(N) gauge group and 2N hypermultiplets. This method is based on an approximation of the integral equation kernel which allows to solve the simplified problem exactly. To determine the accuracy of this approximation, we compare our results to those obtained recently by Passerini and Zarembo. Although less precise, this simpler approach provides an explicit expression for the density of eigenvalues that is used to derive the planar free energy.Comment: 12 pages, v2: section 2.5 (Free Energy) amended and reference added, to appear in J. Phys.

AGT on the S-duality Wall

Three-dimensional gauge theory T[G] arises on a domain wall between four-dimensional N=4 SYM theories with the gauge groups G and its S-dual G^L. We argue that the N=2^* mass deformation of the bulk theory induces a mass-deformation of the theory T[G] on the wall. The partition functions of the theory T[SU(2)] and its mass-deformation on the three-sphere are shown to coincide with the transformation coefficient of Liouville one-point conformal block on torus under the S-duality.Comment: 14 pages, 3 figures. v2: Revised the analysis in sections 3.3 and 4. Notes and references added. Version to appear in JHE

Bipartite quantum states and random complex networks

We introduce a mapping between graphs and pure quantum bipartite states and show that the associated entanglement entropy conveys non-trivial information about the structure of the graph. Our primary goal is to investigate the family of random graphs known as complex networks. In the case of classical random graphs we derive an analytic expression for the averaged entanglement entropy $\bar S$ while for general complex networks we rely on numerics. For large number of nodes $n$ we find a scaling $\bar{S} \sim c \log n +g_e$ where both the prefactor $c$ and the sub-leading O(1) term $g_e$ are a characteristic of the different classes of complex networks. In particular, $g_e$ encodes topological features of the graphs and is named network topological entropy. Our results suggest that quantum entanglement may provide a powerful tool in the analysis of large complex networks with non-trivial topological properties.Comment: 4 pages, 3 figure

A note on perturbation series in supersymmetric gauge theories

Exact results in supersymmetric Chern-Simons and N=2 Yang-Mills theories can be used to examine the quantum behavior of observables and the structure of the perturbative series. For the U(2) x U(2) ABJM model, we determine the asymptotic behavior of the perturbative series for the partition function and write it as a Borel transform. Similar results are obtained for N=2 SU(2) super Yang-Mills theory with four fundamental flavors and in N=2* super Yang-Mills theory, for the partition function as well as for the expectation values for Wilson loop and 't Hooft loop operators (in the 0 and 1 instanton sectors). In all examples, one has an alternate perturbation series where the coefficient of the nth term increases as n!, and the perturbation series are Borel summable. We also calculate the expectation value for a Wilson loop operator in the N=2* SU(N) theory at large N in different regimes of the 't Hooft gauge coupling and mass parameter. For large masses, the calculation reproduces the running gauge coupling for the pure N=2 SYM theory.Comment: 28 pages. V2: minor additions and reference adde

Management of imatinib-resistant CML patients

Imatinib has had marked impact on outcomes in chronic myelogenous leukemia (CML) patients for all stages of the disease and is endorsed by international treatment guidelines as the first line option. Although imatinib is highly effective and well tolerated, the development of resistance represents a clinical challenge. Since the most frequently identified mechanism of acquired imatinib resistance is bcr-abl kinase domain point mutations, periodic hematologic, cytogenetic, and molecular monitoring is critical throughout imatinib therapy. Once cytogenetic remission is achieved, residual disease can be monitored by bcr-abl transcript levels as assayed by reverse transcription polymerase chain reaction (RT-PCR). Detection of bcr-abl mutants prior to and during imatinib therapy can aid in risk stratification as well as in determining therapeutic strategies. Thus, mutation screening is indicated in patients lacking or losing hematologic response. Moreover, search for mutations should also be performed when a 3-log reduction of bcr-abl transcripts is not achieved or there is a reproducible increase of transcript levels. In patients harboring mutations which confer imatinib resistance, novel second line tyrosine kinase inhibitors have demonstrated encouraging efficacy with low toxicity. Only the T315I bcr-abl mutant has proved totally resistant to all clinically available bcr-abl inhibitors. Strategies to further increase the rates of complete molecular remissions represent the next frontier in the targeted therapy of CML patients