Cohomological tautness for Riemannian foliations

In this paper we present some new results on the tautness of Riemannian foliations in their historical context. The first part of the paper gives a short history of the problem. For a closed manifold, the tautness of a Riemannian foliation can be characterized cohomologically. We extend this cohomological characterization to a class of foliations which includes the foliated strata of any singular Riemannian foliation of a closed manifold

Simplicial cohomology of orbifolds

For any orbifold M, we explicitly construct a simplicial complex S(M) from a given triangulation of the ‘coarse ’ underlying space together with the local isotropy groups of M. We prove that, for any local system on M, this complex S(M) has the same cohomology as M. The use of S(M) in explicit calculations is illustrated in the example of the ‘teardrop ’ orbifold. Introduction. Orbifolds or V-manifolds were first introduced by Satake [9], and arise naturally in many ways. For example, the orbit space of any proper action by a (discrete) group on a manifold has the structure of an orbifold; this applies in particular to moduli spaces. Furthermore, the orbit space of any almost free action by

The Volume of some Non-spherical Horizons and the AdS/CFT Correspondence

We calculate the volumes of a large class of Einstein manifolds, namely Sasaki-Einstein manifolds which are the bases of Ricci-flat affine cones described by polynomial embedding relations in C^n. These volumes are important because they allow us to extend and test the AdS/CFT correspondence. We use these volumes to extend the central charge calculation of Gubser (1998) to the generalized conifolds of Gubser, Shatashvili, and Nekrasov (1999). These volumes also allow one to quantize precisely the D-brane flux of the AdS supergravity solution. We end by demonstrating a relationship between the volumes of these Einstein spaces and the number of holomorphic polynomials (which correspond to chiral primary operators in the field theory dual) on the corresponding affine cone.Comment: 25 pp, LaTeX, 1 figure, v2: refs adde

Gauge Formalism for General Relativity and Fermionic Matter

A new formalism for spinors on curved spaces is developed in the framework of variational calculus on fibre bundles. The theory has the same structure of a gauge theory and describes the interaction between the gravitational field and spinors. An appropriate gauge structure is also given to General Relativity, replacing the metric field with spin frames. Finally, conserved quantities and superpotentials are calculated under a general covariant form.Comment: 18 pages, Plain TEX, revision, explicit expression for superpotential has been adde

Novel intravesical bacterial immunotherapy induces rejection of BCG-unresponsive established bladder tumors

Background Intravesical BCG is the gold-standard therapy for non-muscle invasive bladder cancer (NMIBC); however, it still fails in a significant proportion of patients, so improved treatment options are urgently needed. Methods Here, we compared BCG antitumoral efficacy with another live attenuated mycobacteria, MTBVAC, in an orthotopic mouse model of bladder cancer (BC). We aimed to identify both bacterial and host immunological factors to understand the antitumoral mechanisms behind effective bacterial immunotherapy for BC. Results We found that the expression of the BCG-absent proteins ESAT6/CFP10 by MTBVAC was determinant in mediating bladder colonization by the bacteria, which correlated with augmented antitumoral efficacy. We further analyzed the mechanism of action of bacterial immunotherapy and found that it critically relied on the adaptive cytotoxic response. MTBVAC enhanced both tumor antigen-specific CD4 + and CD8 + T-cell responses, in a process dependent on stimulation of type 1 conventional dendritic cells. Importantly, improved intravesical bacterial immunotherapy using MBTVAC induced eradication of fully established bladder tumors, both as a monotherapy and specially in combination with the immune checkpoint inhibitor antiprogrammed cell death ligand 1 (anti PD-L1). Conclusion These results contribute to the understanding of the mechanisms behind successful bacterial immunotherapy against BC and characterize a novel therapeutic approach for BCG-unresponsive NMIBC cases. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Quantum and thermal ionic motion, oxygen isotope effect, and superexchange distribution in La₂CuO₄

We study the zero-point and thermal ionic motion in La$_2$CuO$_4$ by means of high-resolution neutron diffraction experiments. Our results demonstrate anisotropic motion of O and to a lesser extent of Cu ions, both consistent with the structure of coupled CuO$_6$ octahedra, and quantify the relative effects of zero-point and thermal contributions to ionic motion. By substitution of $^{18}$O, we find that the oxygen isotope effect on the lattice dimensions is small and negative ($-0.01\%$), while the isotope effect on the ionic displacement parameters is significant ($-6$ to $50\%$). We use our results as input for theoretical estimates of the distribution of magnetic interaction parameters, $J$, in an effective one-band model for the cuprate plane. We find that ionic motion causes only small ($1\%$) effects on the average value $\langle J\rangle$, which vary with temperature and O isotope, but results in dramatic ($10$-$20\%$) fluctuations in $J$ values that are subject to significant ($8$-$12\%$) isotope effects. We demonstrate that this motional broadening of $J$ can have substantial effects on certain electronic and magnetic properties in cuprates.Comment: 13 pages, 9 figure

Bivalent therapeutic vaccine against HPV16/18 genotypes consisting of a fusion protein between the extra domain A from human fibronectin and HPV16/18 E7 viral antigens.

In vivo targeting of human papillomavirus (HPV) derived antigens to dendritic cells might constitute an efficient immunotherapeutic strategy against cervical cancer. In previous works, we have shown that the extra domain A from murine fibronectin (mEDA) can be used to target antigens to toll-like receptor 4 (TLR4) expressing dendritic cells and induce strong antigen-specific immune responses. In the present study, we have produced a bivalent therapeutic vaccine candidate consisting of the human EDA (hEDA) fused to E7 proteins from HPV16 and HPV18 (hEDA-HPVE7-16/18) and evaluate its potential as a therapeutic vaccine against cervical cancer. Recombinant fusion proteins containing HPV E7 proteins from HPV16 and HPV18 virus subtypes fused to hEDA were produced and tested in vitro on their capacity to bind TLR4 and induce the production of tumor necrosis factor-α or interleukin (IL)-12 by human monocytes and dendritic cells. The immunogenicity and potential therapeutic activity of the vaccine in combination with cisplatin or with the TLR3 agonist molecules polyinosinic-polycytidylic acid (Poly IC) or Poly ICLC was evaluated in mice bearing subcutaneous or genital orthotopic HPV16 TC-1 tumors. hEDA-HPVE7-16/18 prototype vaccine binds human TLR4 and stimulate TLR4-dependent signaling pathways and IL-12 production by human monocyte-derived dendritic cell. Vaccination with hEDA-HPVE7-16/18 induced strong HPVE7-specific Cytotoxic T lymphocyte (CTL) responses and eliminated established tumors in the TC-1-based tumor model. The antitumor efficacy was significantly improved by combining the fusion protein with cisplatin or with the TLR-3 ligand Poly IC and especially with the stabilized analog Poly ICLC. Moreover, hEDA-HPVE7-16/18+Poly ICLC induced full tumor regression in 100% of mice bearing orthotopic genital HPV tumors. Our results suggest that this therapeutic vaccine formulation may be an effective treatment for cervical tumors that do not respond to current therapies

Fibroblast growth factor receptor (FGFR) inhibitor rogaratinib in patients with advanced pretreated squamous-cell non-small cell lung cancer over-expressing FGFR mRNA: The SAKK 19/18 phase II study.

BACKGROUND Patients with advanced squamous-cell lung cancer (SQCLC) frequently (46%) exhibit tumor overexpression of fibroblast growth factor receptor (FGFR) messenger ribonucleic acid (mRNA). Rogaratinib is a novel oral pan-FGFR inhibitor with a good safety profile and anti-tumor activity in early clinical trials as a single agent in FGFR pathway-addicted tumors. SAKK 19/18 determined clinical activity of rogaratinib in patients with advanced SQCLC overexpressing FGFR1-3 mRNA. METHODS Patients with advanced SQCLC failing standard systemic treatment and with FGFR1-3 mRNA tumor overexpression as defined in the protocol received rogaratinib 600 mg BID until disease progression or intolerable toxicity. A 6-months progression-free survival rate (6mPFS) ≤15 % was considered uninteresting (H0), whereas a 6mPFS ≥38 % was considered promising (H1). According to a Simon 2-stage design, 2 out of 10 patients of the first stage were required to be progression-free at 6 months. Comprehensive Genomic Profiling was performedusing the Oncomine Comprehensive Assay Plus (Thermo Fisher Scientific). RESULTS Between July 2019 and November 2020, 49 patients were screened and 20 were classified FGFR-positive. Among a total of 15 patients, 6mPFS was reached in 1 patient (6.7 %), resulting in trial closure for futility after the first stage. There were 7 (46.7 %) patients with stable disease and 5 (33.3 %) patients with progressive disease. Median PFS was 1.6 (95 % CI 0.9-3.5) months and median overall survival (OS) 3.5 (95 % CI 1.0-5.9) months. Most frequent treatment-related adverse events (TRAEs) included hyperphosphatemia in 8 (53 %), diarrhea in 5 (33 %), stomatitis in 3 (20 %) and nail changes in 3 (20 %) patients. Grade ≥3 TRAEs occurred in 6 (40 %) patients. No associations between mutational profile and treatment outcome were observed. CONCLUSION Despite preliminary signals of activity, rogaratinib failed to improve PFS in patients with advanced SQCLC overexpressing FGFR mRNA. FGFR inhibitors in SQCLC remain a challenging field, and more in-depth understanding of pathway crosstalks may lead to the development of drug combinations with FGFR inhibitors resulting in improved outcomes

Secondary LS category of measured laminations

In the author's Ph.D., a version of the tangential LS category for foliated spaces depending on a transverse invariant measure, called the measured category, was introduced. Unfortunately, the measured category vanishes easily. When it is zero, the rate of convergence to zero of the quantity involved in the definition, by taking arbitrarily large homotopies, gives a new invariant, called the secondary measured category. Several versions of classical results are proved for the secondary measured category. It is also shown that the secondary measured category is a transverse invariant related to the growth of (pseudo)groups. The equality between secondary category and the growth of a group is done in the case of free suspensions by Rohlin groups.Comment: 14 pages. arXiv admin note: substantial text overlap with arXiv:1112.500

Quantized reduction as a tensor product

Symplectic reduction is reinterpreted as the composition of arrows in the category of integrable Poisson manifolds, whose arrows are isomorphism classes of dual pairs, with symplectic groupoids as units. Morita equivalence of Poisson manifolds amounts to isomorphism of objects in this category. This description paves the way for the quantization of the classical reduction procedure, which is based on the formal analogy between dual pairs of Poisson manifolds and Hilbert bimodules over C*-algebras, as well as with correspondences between von Neumann algebras. Further analogies are drawn with categories of groupoids (of algebraic, measured, Lie, and symplectic type). In all cases, the arrows are isomorphism classes of appropriate bimodules, and their composition may be seen as a tensor product. Hence in suitable categories reduction is simply composition of arrows, and Morita equivalence is isomorphism of objects.Comment: 44 pages, categorical interpretation adde