Immune checkpoint inhibitors in ovarian cancer: where do we stand?

Numerous retrospective studies have demonstrated that the density of intra-tumoral immune cell infiltration is prognostic in epithelial ovarian cancer (OC). These observations together with reports of programmed death ligand-1 (PD-L1) expression in advanced OC provided the rationale for investigating the benefit of programmed death-1 (PD1) or PD-L1 inhibition in OC. Unfortunately clinical trials to date evaluating PD1/PD-L1 inhibition in patients with relapsed OC have been disappointing. In this review we will discuss early results from single agent PD1/PD-L1 inhibitors and the strategies to enhance benefit from immune-oncology agents in OC, including proposing anti-PD-L1 in combination with other agents (cytotoxics, anti-angiogenics, poly(ADP-ribose) polymerase. (PARP) inhibitors, targeted therapies or other immunotherapies), as well as evaluating these agents earlier in the disease course, or in biomarker selected patients

Diagonal and Low-Rank Matrix Decompositions, Correlation Matrices, and Ellipsoid Fitting

In this paper we establish links between, and new results for, three problems that are not usually considered together. The first is a matrix decomposition problem that arises in areas such as statistical modeling and signal processing: given a matrix $X$ formed as the sum of an unknown diagonal matrix and an unknown low rank positive semidefinite matrix, decompose $X$ into these constituents. The second problem we consider is to determine the facial structure of the set of correlation matrices, a convex set also known as the elliptope. This convex body, and particularly its facial structure, plays a role in applications from combinatorial optimization to mathematical finance. The third problem is a basic geometric question: given points $v_1,v_2,...,v_n\in \R^k$ (where $n > k$) determine whether there is a centered ellipsoid passing \emph{exactly} through all of the points. We show that in a precise sense these three problems are equivalent. Furthermore we establish a simple sufficient condition on a subspace $U$ that ensures any positive semidefinite matrix $L$ with column space $U$ can be recovered from $D+L$ for any diagonal matrix $D$ using a convex optimization-based heuristic known as minimum trace factor analysis. This result leads to a new understanding of the structure of rank-deficient correlation matrices and a simple condition on a set of points that ensures there is a centered ellipsoid passing through them.Comment: 20 page

Kondo effect in a one dimensional d-wave superconductor

We derive a solvable resonant-level type model, to describe an impurity spin coupled to zero-energy bound states localized at the edge of a one dimensional d-wave superconductor. This results in a two-channel Kondo effect with a quite unusual low-temperature thermodynamics. For instance, the local impurity susceptibility yields a finite maximum at zero temperature (but no logarithmic-divergence) due to the splitting of the impurity in two Majorana fermions. Moreover, we make comparisons with the Kondo effect occurring in a two dimensional d-wave superconductor.Comment: 9 pages, final version; To be published in Europhysics Letter

Theory of anomalous magnetic interference pattern in mesoscopic SNS Josephson junctions

The magnetic interference pattern in mesoscopic SNS Josephson junctions is sensitive to the scattering in the normal part of the system. In this paper we investigate it, generalizing Ishii's formula for current-phase dependence to the case of normal scattering at NS boundaries in an SNS junction of finite width. The resulting flattening of the first diffraction peak is consistent with experimental data for S-2DEG-S mesoscopic junctions.Comment: 6 pages, 5 figures. Phys. Rev. B 68, 144514 (2003

Weighted complex projective 2-designs from bases: optimal state determination by orthogonal measurements

We introduce the problem of constructing weighted complex projective 2-designs from the union of a family of orthonormal bases. If the weight remains constant across elements of the same basis, then such designs can be interpreted as generalizations of complete sets of mutually unbiased bases, being equivalent whenever the design is composed of d+1 bases in dimension d. We show that, for the purpose of quantum state determination, these designs specify an optimal collection of orthogonal measurements. Using highly nonlinear functions on abelian groups, we construct explicit examples from d+2 orthonormal bases whenever d+1 is a prime power, covering dimensions d=6, 10, and 12, for example, where no complete sets of mutually unbiased bases have thus far been found.Comment: 28 pages, to appear in J. Math. Phy

Blinking statistics of a molecular beacon triggered by end-denaturation of DNA

We use a master equation approach based on the Poland-Scheraga free energy for DNA denaturation to investigate the (un)zipping dynamics of a denaturation wedge in a stretch of DNA, that is clamped at one end. In particular, we quantify the blinking dynamics of a fluorophore-quencher pair mounted within the denaturation wedge. We also study the behavioural changes in the presence of proteins, that selectively bind to single-stranded DNA. We show that such a setup could be well-suited as an easy-to-implement nanodevice for sensing environmental conditions in small volumes.Comment: 14 pages, 5 figures, LaTeX, IOP style. Accepted to J Phys Cond Mat special issue on diffusio