Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.

Protein-protein interactions (PPIs) are of pivotal importance in the regulation of biological systems and are consequently implicated in the development of disease states. Recent work has begun to show that, with the right tools, certain classes of PPI can yield to the efforts of medicinal chemists to develop inhibitors, and the first PPI inhibitors have reached clinical development. In this Review, we describe the research leading to these breakthroughs and highlight the existence of groups of structurally related PPIs within the PPI target class. For each of these groups, we use examples of successful discovery efforts to illustrate the research strategies that have proved most useful.JS, DES and ARB thank the Wellcome Trust for funding.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nrd.2016.2

Clinical applications of PD-L1 bioassays for cancer immunotherapy

Abstract Programmed death ligand 1 (PD-L1) has emerged as a biomarker that can help to predict responses to immunotherapies targeted against PD-L1 and its receptor (PD-1). Companion tests for evaluating PD-L1 expression as a biomarker of response have been developed for many cancer immunotherapy agents. These assays use a variety of detection platforms at different levels (protein, mRNA), employ diverse biopsy and surgical samples, and have disparate positivity cutoff points and scoring systems, all of which complicate the standardization of clinical decision-making. This review summarizes the current understanding and ongoing investigations regarding PD-L1 expression as a potential biomarker for clinical outcomes of anti-PD-1/PD-L1 immunotherapy

Genome-wide association studies of cancer: current insights and future perspectives.

Genome-wide association studies (GWAS) provide an agnostic approach for investigating the genetic basis of complex diseases. In oncology, GWAS of nearly all common malignancies have been performed, and over 450 genetic variants associated with increased risks have been identified. As well as revealing novel pathways important in carcinogenesis, these studies have shown that common genetic variation contributes substantially to the heritable risk of many common cancers. The clinical application of GWAS is starting to provide opportunities for drug discovery and repositioning as well as for cancer prevention. However, deciphering the functional and biological basis of associations is challenging and is in part a barrier to fully unlocking the potential of GWAS

Solar and heliospheric observatory/coronal diagnostic spectrograph and ground-based observations of a two-ribbon flare: Spatially resolved signatures of chromospheric evaporation

During a coordinated observing campaign (Solar and Heliospheric Observatory, SOHO JOP 139), we obtained simultaneous spectroheliograms of a solar active region in several spectral lines, sampling levels from the chromosphere to the corona. Ground-based spectroheliograms were acquired at the Dunn Solar Tower of the National Solar Observatory/Sacramento Peak in four chromospheric lines, while the coronal diagnostic spectrograph on board SOHO was used to obtain rasters of the active region in transition region (TR) and coronal lines. Such a complete data set allowed us to compare the development of intensity and velocity fields during a small two-ribbon flare in the whole atmosphere. In particular, we obtained for the first time quasi-simultaneous and spatially resolved observations of velocity fields during the impulsive phase of a flare, in both the chromosphere and upper atmosphere. In this phase, strong downflows (up to 40 km s-1) following the shape of the developing ribbons are measured at chromospheric levels, while strong upward motions are instead measured in TR (up to -100 km s-1) and coronal lines (-160 km s-1). The spatial pattern of these velocities have a common area about 10'' wide. This is the first time that opposite-directed flows at different atmospheric levels are observed in the same spatial location during a flare. These signatures are highly suggestive of the chromospheric evaporation scenario predicted in theoretical models of flares

The Face Deepfake Detection Challenge

Multimedia data manipulation and forgery has never been easier than today, thanks to the power of Artificial Intelligence (AI). AI-generated fake content, commonly called Deepfakes, have been raising new issues and concerns, but also new challenges for the research community. The Deepfake detection task has become widely addressed, but unfortunately, approaches in the literature suffer from generalization issues. In this paper, the Face Deepfake Detection and Reconstruction Challenge is described. Two different tasks were proposed to the participants: (i) creating a Deepfake detector capable of working in an "in the wild" scenario; (ii) creating a method capable of reconstructing original images from Deepfakes. Real images from CelebA and FFHQ and Deepfake images created by StarGAN, StarGAN-v2, StyleGAN, StyleGAN2, AttGAN and GDWCT were collected for the competition. The winning teams were chosen with respect to the highest classification accuracy value (Task I) and "minimum average distance to Manhattan" (Task II). Deep Learning algorithms, particularly those based on the EfficientNet architecture, achieved the best results in Task I. No winners were proclaimed for Task II. A detailed discussion of teams' proposed methods with corresponding ranking is presented in this paper