Supersymmetric AdS_5 solutions of M-theory

We analyse the most general supersymmetric solutions of D=11 supergravity consisting of a warped product of five-dimensional anti-de-Sitter space with a six-dimensional Riemannian space M_6, with four-form flux on M_6. We show that M_6 is partly specified by a one-parameter family of four-dimensional Kahler metrics. We find a large family of new explicit regular solutions where M_6 is a compact, complex manifold which is topologically a two-sphere bundle over a four-dimensional base, where the latter is either (i) Kahler-Einstein with positive curvature, or (ii) a product of two constant-curvature Riemann surfaces. After dimensional reduction and T-duality, some solutions in the second class are related to a new family of Sasaki-Einstein spaces which includes T^{1,1}/Z_2. Our general analysis also covers warped products of five-dimensional Minkowski space with a six-dimensional Riemannian space.Comment: 40 pages. v2: minor changes, eqs. (2.22) and (D.12) correcte

Branes on Generalized Calibrated Submanifolds

We extend previous results on generalized calibrations to describe supersymmetric branes in supergravity backgrounds with diverse fields turned on, and provide several new classes of examples. As an important application, we show that supersymmetric D-branes in compactifications with field strength fluxes, and on SU(3)-structure spaces, wrap generalized calibrated submanifolds, defined by simple conditions in terms of the underlying globally defined, but non-closed, 2- and 3-forms. We provide examples where the geometric moduli of D-branes (for instance D7-branes in 3-form flux configurations) are lifted by the generalized calibration condition. In addition, we describe supersymmetric D6-branes on generalized calibrated 3-submanifolds of half-flat manifolds, which provide the mirror of B-type D-branes in IIB CY compactifications with 3-form fluxes. Supersymmetric sets of such D-branes carrying no homology charges are mirror to supersymmetric sets of D-branes which are homologically non-trivial, but trivial in K-theory. As an additional application, we describe models with chiral gauge sectors, realized in terms of generalized calibrated brane box configurations of NS- and D5-branes, which are supersymmetric but carry no charges, so that no orientifold planes are required in the compactification.Comment: 40 pages, 3 figures, references adde

FHIT gene therapy prevents tumor development in Fhit-deficient mice

The tumor suppressor gene FHIT spans a common fragile site and is highly susceptible to environmental carcinogens. FHIT inactivation and loss of expression is found in a large fraction of premaligant and malignant lesions. In this study, we were able to inhibit tumor development by oral gene transfer, using adenoviral or adenoassociated viral vectors expressing the human FHIT gene, in heterozygous Fhit+/- knockout mice, that are prone to tumor development after carcinogen exposure. We therefore suggest that FHIT gene therapy could be a novel clinical approach not only in treatment of early stages of cancer, but also in prevention of human cancer

The Hitchin functionals and the topological B-model at one loop

The quantization in quadratic order of the Hitchin functional, which defines by critical points a Calabi-Yau structure on a six-dimensional manifold, is performed. The conjectured relation between the topological B-model and the Hitchin functional is studied at one loop. It is found that the genus one free energy of the topological B-model disagrees with the one-loop free energy of the minimal Hitchin functional. However, the topological B-model does agree at one-loop order with the extended Hitchin functional, which also defines by critical points a generalized Calabi-Yau structure. The dependence of the one-loop result on a background metric is studied, and a gravitational anomaly is found for both the B-model and the extended Hitchin model. The anomaly reduces to a volume-dependent factor if one computes for only Ricci-flat Kahler metrics.Comment: 33 pages, LaTe

Generalized Kaehler Potentials from Supergravity

We consider supersymmetric N=2 solutions with non-vanishing NS three-form. Building on worldsheet results, we reduce the problem to a single generalized Monge-Ampere equation on the generalized Kaehler potential K recently interpreted geometrically by Lindstrom, Rocek, Von Unge and Zabzine. One input in the procedure is a holomorphic function w that can be thought of as the effective superpotential for a D3 brane probe. The procedure is hence likely to be useful for finding gravity duals to field theories with non-vanishing abelian superpotential, such as Leigh-Strassler theories. We indeed show that a purely NS precursor of the Lunin-Maldacena dual to the beta-deformed N=4 super-Yang-Mills falls in our class.Comment: "38 pages. v3: improved exposition and minor mistakes corrected in sec. 4

New Examples of Flux Vacua

Type IIB toroidal orientifolds are among the earliest examples of flux vacua. By applying T-duality, we construct the first examples of massive IIA flux vacua with Minkowski space-times, along with new examples of type IIA flux vacua. The backgrounds are surprisingly simple with no four-form flux at all. They serve as illustrations of the ingredients needed to build type IIA and massive IIA solutions with scale separation. To check that these backgrounds are actually solutions, we formulate the complete set of type II supergravity equations of motion in a very useful form that treats the R-R fields democratically.Comment: 38 pages, LaTeX; references updated; additional minor comments added; published versio

Evaluating immunological and inflammatory changes of treatment-experienced people living with HIV switching from first-line triple cART regimens to DTG/3TC vs. B/F/TAF: the DEBATE trial

Background: The aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR). Methods: An open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders. Results: Between the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm–time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = −6.7 cells/mm3; 95% CI; −16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12. Conclusion: No evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04054089

Evaluating immunological and inflammatory changes of treatment-experienced people living with HIV switching from first-line triple cART regimens to DTG/3TC vs. B/F/TAF: the DEBATE trial

Background: The aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR).Methods: An open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders.Results: Between the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm-time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = -6.7 cells/mm(3); 95% CI; -16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12.Conclusion: No evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results

A primary cutaneous adenoid-cystic carcinoma in a young woman. Differential diagnosis and clinical implications

Primary cutaneous adenoid-cystic carcinoma (PCACC) is a rare slow-growing neoplasm of disputed histogenesis characterized by a cribriform pattern at histology and local aggressive behaviour. Up to date about 60 cases of PCACC have been reported in the literature. This tumour is most common in the scalp, affects middle-aged and older individuals (mean age 59) and has predilection for women. We describe an unexpected case of PCACC in a 32-years-old woman referred to our clinic for a subcutaneous nodule in the scalp showing a slow growth and indolent course. The differential diagnosis and the clinical management of this PCACC patient, successfully treated with a wide local excision, are presented and discussed

Non-Perturbative Superpotentials in F-theory and String Duality

We use open-closed string duality between F-theory on K3xK3 and type II strings on CY manifolds without branes to study non-perturbative superpotentials in generalized flux compactifications. On the F-theory side we obtain the full flux potential including D3-instanton contributions and show that it leads to an explicit and simple realization of the three ingredients of the KKLT model for stringy dS vacua. The D3-instanton contribution is highly non-trivial, can be systematically computed including the determinant factors and demonstrates that a particular flux lifts very effectively zero modes on the instanton. On the closed string side, we propose a generalization of the Gukov-Vafa-Witten superpotential for type II strings on generalized CY manifolds, depending on all moduli multiplets.Comment: 49 pages, harvmac, 1 figure; references & figures adde