No-go for Partially Massless Spin-2 Yang-Mills

There are various no-go results forbidding self-interactions for a single partially massless spin-2 field. Given the photon-like structure of the linear partially massless field, it is natural to ask whether a multiplet of such fields can interact under an internal Yang-Mills like extension of the partially massless symmetry. We give two arguments that such a partially massless Yang-Mills theory does not exist. The first is that there is no Yang-Mills like non-abelian deformation of the partially massless symmetry, and the second is that cubic vertices with the appropriate structure constants do not exist.Comment: 18 pages. v2 small corrections and ref

Programmed Death-Ligand 1 Expression in Lung Cancer and Paired Brain Metastases-a Single-Center Study in 190 Patients.

Expression of programmed death-ligand 1 (PD-L1) is the only routinely used tissue biomarker for predicting response to programmed cell death protein 1/PD-L1 inhibitors. It is to date unclear whether PD-L1 expression is preserved in brain metastases (BMs). In this single-center, retrospective study, we evaluated PD-L1 expression using the SP263 assay in consecutively resected BMs of lung carcinomas and paired primary tumors, diagnosed from 2000 to 2015, with correlation to clinicopathological and molecular tumor and patient characteristics. PD-L1 tumor proportional score (TPS) could be evaluated on whole tissue slides in 191 BMs and 84 paired primary lung carcinomas. PD-L1 TPS was less than 1% in 113 of 191 (59.2%), 1% to 49% in 34 of 191 (17.8%), and greater than or equal to 50% in 44 of 191 (23.0%) BMs. TPS was concordant between BMs and paired primary lung carcinomas in most cases, with discordance regarding the clinically relevant cutoffs at 1% and 50% in 18 of 84 patients (21.4%). Four of 18 discordant cases had no shared mutations between the primary lung carcinoma and BM. Intratumoral heterogeneity, as assessed using tissue microarray cores, was only significant at the primary site (p <sub>Wilcoxon signed rank</sub> = 0.002) with higher PD-L1 TPS at the infiltration front (mean = 40.4%, interquartile range: 0%-90%). Neither TPS greater than or equal to 1% nor TPS greater than or equal to 50% nor discordance between the primary lung carcinoma and BMs had prognostic significance regarding overall survival or BM-specific overall survival. PD-L1 expression was mostly concordant between primary lung carcinoma and its BM and between resections of BM and stereotactic biopsies, mirrored by tissue microarray cores. Differences in PD-L1 TPS existed primarily in cases with TPS greater than 10%, for which also human assessment tends to be most error prone

Zero-point quantum fluctuations in cosmology

We re-examine the classic problem of the renormalization of zero-point quantum fluctuations in a Friedmann-Robertson-Walker background. We discuss a number of issues that arise when regularizing the theory with a momentum-space cutoff, and show explicitly how introducing non-covariant counter-terms allows to obtain covariant results for the renormalized vacuum energy-momentum tensor. We clarify some confusion in the literature concerning the equation of state of vacuum fluctuations. Further, we point out that the general structure of the effective action becomes richer if the theory contains a scalar field phi with mass m smaller than the Hubble parameter H(t). Such an ultra-light particle cannot be integrated out completely to get the effective action. Apart from the volume term and the Einstein-Hilbert term, that are reabsorbed into renormalizations of the cosmological constant and Newton's constant, the effective action in general also has a term proportional to F(phi)R, for some function F(phi). As a result, vacuum fluctuations of ultra-light scalar fields naturally lead to models where the dark energy density has the form rho_{DE}(t)=rho_X(t)+rho_Z(t), where rho_X is the component that accelerates the Hubble expansion at late times and rho_Z(t) is an extra contribution proportional to H^2(t). We perform a detailed comparison of such models with CMB, SNIa and BAO data.Comment: 23 pages, 9 figures. v3: refs added. To appear in Phys. Rev.

Optimized Inhibitors of MDM2 via an Attempted Protein-Templated Reductive Amination

Innovative and efficient hit-identification techniques are required to accelerate drug discovery. Protein-templated fragment ligations represent a promising strategy in early drug discovery, enabling the target to assemble and select its binders from a pool of building blocks. Development of new protein-templated reactions to access a larger structural diversity and expansion of the variety of targets to demonstrate the scope of the technique are of prime interest for medicinal chemists. Herein, we present our attempts to use a protein-templated reductive amination to target protein-protein interactions (PPIs), a challenging class of drug targets. We address a flexible pocket, which is difficult to achieve by structure-based drug design. After careful analysis we did not find one of the possible products in the kinetic target-guided synthesis (KTGS) approach, however subsequent synthesis and biochemical evaluation of each library member demonstrated that all the obtained molecules inhibit MDM2. The most potent library member (Ki=0.095 μm) identified is almost as active as Nutlin-3, a potent inhibitor of the p53-MDM2 PPI

LNCS

Static program analyzers are increasingly effective in checking correctness properties of programs and reporting any errors found, often in the form of error traces. However, developers still spend a significant amount of time on debugging. This involves processing long error traces in an effort to localize a bug to a relatively small part of the program and to identify its cause. In this paper, we present a technique for automated fault localization that, given a program and an error trace, efficiently narrows down the cause of the error to a few statements. These statements are then ranked in terms of their suspiciousness. Our technique relies only on the semantics of the given program and does not require any test cases or user guidance. In experiments on a set of C benchmarks, we show that our technique is effective in quickly isolating the cause of error while out-performing other state-of-the-art fault-localization techniques