Diagnosis and Location of Pinhole Defects in Tunnel Junctions using only Electrical Measurements

In the development of the first generation of sensors and memory chips based on spin-dependent tunneling through a thin trilayer, it has become clear that pinhole defects can have a deleterious effect on magnetoresistance. However, current diagnostic protocols based on Andreev reflection and the temperature dependence of junction resistance may not be suitable for production quality control. We show that the current density in a tunnel junction in the cross-strip geometry becomes very inhomogeneous in the presence of a single pinhole, yielding a four-terminal resistance that depends on the location of the pinhole in the junction. Taking advantage of this position dependence, we propose a simple protocol of four four-terminal measurements. Solving an inverse problem, we can diagnose the presence of a pinhole and estimate its position and resistance.Comment: 9 pages, eplain TeX, other macro files included; some versions of TeX epsf may have trouble with figures, in which case try the Postscript or PDF generated automatically by the Archiv

An Optimal and Distributed Method for Voltage Regulation in Power Distribution Systems

This paper addresses the problem of voltage regulation in power distribution networks with deep-penetration of distributed energy resources, e.g., renewable-based generation, and storage-capable loads such as plug-in hybrid electric vehicles. We cast the problem as an optimization program, where the objective is to minimize the losses in the network subject to constraints on bus voltage magnitudes, limits on active and reactive power injections, transmission line thermal limits and losses. We provide sufficient conditions under which the optimization problem can be solved via its convex relaxation. Using data from existing networks, we show that these sufficient conditions are expected to be satisfied by most networks. We also provide an efficient distributed algorithm to solve the problem. The algorithm adheres to a communication topology described by a graph that is the same as the graph that describes the electrical network topology. We illustrate the operation of the algorithm, including its robustness against communication link failures, through several case studies involving 5-, 34-, and 123-bus power distribution systems.Comment: To Appear in IEEE Transaction on Power System

Neoadjuvant sipuleucel-T induces both Th1 activation and immune regulation in localized prostate cancer.

Sipuleucel-T is the only FDA-approved immunotherapy for metastatic castration-resistant prostate cancer. The mechanism by which this treatment improves survival is not fully understood. We have previously shown that this treatment can induce the recruitment of CD4 and CD8 T cells to the tumor microenvironment. In this study, we examined the functional state of these T cells through gene expression profiling. We found that the magnitude of T cell signatures correlated with the frequency of T cells as measured by immunohistochemistry. Sipuleucel-T treatment was associated with increased expression of Th1-associated genes, but not Th2-, Th17 - or Treg-associated genes. Post-treatment tumor tissues with high CD8+T cell infiltration was associated with high levels of CXCL10 expression. On in situ hybridization, CXCL10+ cells colocalized with CD8+T cells in post-treatment prostatectomy tumor tissue. Neoadjuvant sipuleucel-T was also associated with upregulation of immune inhibitory checkpoints, including CTLA4 and TIGIT, and downregulation of the immune activation marker, dipeptidylpeptidase, DPP4. Treatment-associated declines in serum PSA were correlated with induction of Th1 response. In contrast, rises in serum PSA while on treatment were associated with the induction of multiple immune checkpoints, including CTLA4, CEACAM6 and TIGIT. This could represent adaptive immune resistance mechanisms induced by treatment. Taken together, neoadjuvant sipuleucel-T can induce both a Th1 response and negative immune regulation in the prostate cancer microenvironment

Large Deviations for Stochastic Heat Equation with Rough Dependence in Space

In this paper we establish a large deviation principle for the nonlinear one dimensional stochastic heat equation driven by a Gaussian noise which is white in time and which has the covariance of a fractional Brownian motion with Hurst parameter H ∈( 14 ; 12) in the space variable

Adaptation Algorithm and Theory Based on Generalized Discrepancy

We present a new algorithm for domain adaptation improving upon a discrepancy minimization algorithm previously shown to outperform a number of algorithms for this task. Unlike many previous algorithms for domain adaptation, our algorithm does not consist of a fixed reweighting of the losses over the training sample. We show that our algorithm benefits from a solid theoretical foundation and more favorable learning bounds than discrepancy minimization. We present a detailed description of our algorithm and give several efficient solutions for solving its optimization problem. We also report the results of several experiments showing that it outperforms discrepancy minimization

Combination immunotherapy induces distinct T-cell repertoire responses when administered to patients with different malignancies.

BackgroundCTLA-4 blockade with ipilimumab is Food and Drug Administration-approved for melanoma as a monotherapy and has been shown to modulate the circulating T-cell repertoire. We have previously reported clinical trials combining CTLA-4 blockade with granulocyte-macrophage colony-stimulating factor (GM-CSF) in metastatic melanoma patients and in metastatic castration resistant prostate cancer (mCRPC) patients. Here, we investigate the effect that cancer type has on circulating T cells in metastatic melanoma and mCRPC patients, treated with ipilimumab and GM-CSF.MethodsWe used next-generation sequencing of T-cell receptors (TCR) to compare the circulating T cells of melanoma and mCRPC patients receiving the same treatment with ipilimumab and GM-CSF by Wilcoxon rank sum test. Flow cytometry was utilized to investigate specific T-cell populations. TCR sequencing results were correlated with each T-cell subpopulation by Spearman's rank correlation coefficient. Of note, 14 metastatic melanoma patients had samples available for TCR sequencing and 21 had samples available for flow cytometry analysis; 37 mCRPC patients had samples available for sequencing of whom 22 have TCR data available at both timepoints; 20 of these patients had samples available for flow cytometry analysis and 16 had data available at both timepoints.ResultsWhile melanoma and mCRPC patients had similar pretreatment circulating T-cell counts, treatment induces greater expansion of circulating T cells in melanoma patients. Metastatic melanoma patients have a higher proportion of clones that increased more than fourfold after the treatment compared with mCRPC patients (18.9% vs 11.0%, p=0.017). Additionally, melanoma patients compared with mCRPC patients had a higher ratio of convergent frequency (1.22 vs 0.60, p=0.012). Decreases in clonality induced by treatment are associated with baseline CD8+ T-cell counts in both patient groups, but are more pronounced in the melanoma patients (r=-0.81, p<0.001 vs r=-0.59, p=0.02).Trial registration numbersNCT00064129; NCT01363206