Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Exposing an “Intangible” Cognitive Skill Among Collegiate Football Players: III. Enhanced Reaction Control to Motion

Football is played in a dynamic, often unpredictable, visual environment in which players are challenged to process and respond with speed and flexibility to critical incoming stimulus events. To meet this challenge, we hypothesize that football players possess, in conjunction with their extraordinary physical skills, exceptionally proficient executive cognitive control systems that optimize response execution. It is particularly important for these systems to be proficient at coordinating directional reaction and counter-reaction decisions to the very rapid lateral movements routinely made by their opponents during a game. Despite the importance of this executive skill to successful on-field performance, it has not been studied in football players. To fill this void, we compared the performances of Division I college football players (n = 525) and their non-athlete age counterparts (n = 40) in a motion-based stimulus-response compatibility task that assessed their proficiency at executing either compatible (in the same direction) or incompatible (in the opposite direction) lateralized reactions to a target's lateral motion. We added an element of decision uncertainty and complexity by giving them either sufficient or insufficient time to preload the response decision rule (i.e., compatible vs. incompatible) prior to the target setting in motion. Overall, football players were significantly faster than non-athlete controls in their choice reactions to a target's lateral motion. The reactions of all participants slowed when issuing incompatible counter-reactions to a target's lateral motion. For football players, this cost was reduced substantially compared to controls when given insufficient time to preload the decision rule, indicating that they exerted more efficient executive control over their reactions and counter-reactions when faced with decision uncertainty at the onset of stimulus motion. We consider putative sources of their advantage in reacting to a target's lateral motion and discuss how these findings advance the hypothesis that football players utilize highly-proficient executive control systems to overcome processing conflicts during motor performance

Vessel-Encoded Arterial Spin Labeling (VE-ASL) Reveals Elevated Flow Territory Asymmetry in Older Adults With Substandard Verbal Memory Performance

Neuro Imaging Researc

Security for Diversity: Studying the Effects of Verbal and Imagery Processes on User Authentication Mechanisms

Abstract. Stimulated by a large number of different theories on human cognition, suggesting that individuals have different habitual approaches in retrieving, recalling, processing and storing verbal and graphical information, this paper investigates the effect of such processes with regard to user performance and preference toward two variations of knowledge-based authentication mechanisms. In particular, a text-based password authentication mechanism and a recognition-based graphical authentication mechanism were deployed in the frame of an ecological valid user study, to investigate the effect of specific cognitive factors of users toward efficiency, effectiveness and preference of authentication tasks. A total of 145 users participated during a five-month period between February and June 2012. This recent study provides interesting insights for the design and deployment of adaptive authentication mechanisms based on cognitive factors of users. The results and implications of this paper are valuable in understanding and modeling user interactions with regard to authentication mechanisms

Search for new Higgs bosons via same-sign top quark pair production in association with a jet in proton-proton collisions at s=13TeV

A search is presented for new Higgs bosons in proton-proton (pp) collision events in which a same-sign top quark pair is produced in association with a jet, via the pp→tH/A→ttc‾ and pp→tH/A→ttu‾ processes. Here, H and A represent the extra scalar and pseudoscalar boson, respectively, of the second Higgs doublet in the generalized two-Higgs-doublet model (g2HDM). The search is based on pp collision data collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC, corresponding to an integrated luminosity of 138fb−1. Final states with a same-sign lepton pair in association with jets and missing transverse momentum are considered. New Higgs bosons in the 200–1000 GeV mass range and new Yukawa couplings between 0.1 and 1.0 are targeted in the search, for scenarios in which either H or A appear alone, or in which they coexist and interfere. No significant excess above the standard model prediction is observed. Exclusion limits are derived in the context of the g2HDM