Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes.

Inhibitor of Apoptosis Proteins act as E3 ubiquitin ligases to regulate NF-κB signalling from multiple pattern recognition receptors including NOD2, as well as TNF Receptor Superfamily members. Loss of XIAP in humans causes X-linked Lymphoproliferative disease type 2 (XLP-2) and is often associated with Crohn's disease. Crohn's disease is also caused by mutations in the gene encoding NOD2 but the mechanisms behind Crohn's disease development in XIAP and NOD2 deficient-patients are still unknown.

Should We Keep Walking along the Trail for Pancreatic Cancer Treatment? Revisiting TNF-Related Apoptosis-Inducing Ligand for Anticancer Therapy.

Despite recent advances in oncology, diagnosis, and therapy, treatment of pancreatic ductal adenocarcinoma (PDAC) is still exceedingly challenging. PDAC remains the fourth leading cause of cancer-related deaths worldwide. Poor prognosis is due to the aggressive growth behavior with early invasion and distant metastasis, chemoresistance, and a current lack of adequate screening methods for early detection.

DNA plasticity and damage in amyotrophic lateral sclerosis.

The pathophysiology of amyotrophic lateral sclerosis (ALS) is particularly challenging due to the heterogeneity of its clinical presentation and the diversity of cellular, molecular and genetic peculiarities involved. Molecular insights unveiled several novel genetic factors to be inherent in both familial and sporadic disease entities, whose characterizations in terms of phenotype prediction, pathophysiological impact and putative prognostic value are a topic of current researches. However, apart from genetically well-defined high-confidence and other susceptibility loci, the role of DNA damage and repair strategies of the genome as a whole, either elicited as a direct consequence of the underlying genetic mutation or seen as an autonomous parameter, in the initiation and progression of ALS, and the different cues involved in either process are still incompletely understood.

A simple parametric model observer for quality assurance in computer tomography.

Model observers are mathematical classifiers that are used for the quality assessment of imaging systems such as computer tomography. The quality of the imaging system is quantified by means of the performance of a selected model observer. For binary classification tasks, the performance of the model observer is defined by the area under its ROC curve (AUC).

Neuronal Growth and Behavioral Alterations in Mice Deficient for the Psychiatric Disease-Associated Gene.

Neuronal growth regulator 1 (NEGR1), a member of the immunoglobulin superfamily cell adhesion molecule subgroup IgLON, has been implicated in neuronal growth and connectivity. In addition, genetic variants in or near the NEGR1 locus have been associated with obesity and more recently with learning difficulties, intellectual disability and psychiatric disorders. However, experimental evidence is lacking to support a possible link between NEGR1, neuronal growth and behavioral abnormalities.

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.

Background: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis.

Methods: We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less.

CK1α overexpression correlates with poor survival in colorectal cancer.

Background: Colorectal cancer (CRC) is the fourth leading cause of cancer related deaths worldwide and prognosis in advanced tumor stage still remains poor. Since CK1 isoforms have been reported to be deregulated in several tumor entities CK1 has emerged as a novel drug target in cancer therapy. In this study we set out to investigate whether CK1α might have the potential to serve as prognostic marker.

Machine-learning approach for local classification of crystalline structures in multiphase systems.

Machine learning is one of the most popular fields in computer science and has a vast number of applications. In this work we will propose a method that will use a neural network to locally identify crystal structures in a mixed phase Yukawa system consisting of fcc, hcp, and bcc clusters and disordered particles similar to plasma crystals. We compare our approach to already used methods and show that the quality of identification increases significantly.

Measurement of the -boson mass in pp collisions at with the ATLAS detector.

A measurement of the mass of the boson is presented based on proton-proton collision data recorded in 2011 at a centre-of-mass energy of 7 TeV with the ATLAS detector at the LHC, and corresponding to of integrated luminosity. The selected data sample consists of candidates in the channel and candidates in the channel. The -boson mass is obtained from template fits to the reconstructed distributions of the charged lepton transverse momentum and of the boson transverse mass in the electron and muon decay channels, yielding where the first uncertainty is statistical, the second corresponds to the experimental systematic uncertainty, and the third to the physics-modelling systematic uncertainty.

Measurements of the production cross section of a [Formula: see text] boson in association with jets in collisions at [Formula: see text] TeV with the ATLAS detector.

Measurements of the production cross section of a [Formula: see text] boson in association with jets in proton-proton collisions at [Formula: see text] TeV are presented, using data corresponding to an integrated luminosity of 3.16 fb[Formula: see text] collected by the ATLAS experiment at the CERN Large Hadron Collider in 2015. Inclusive and differential cross sections are measured for events containing a [Formula: see text] boson decaying to electrons or muons and produced in association with up to seven jets with [Formula: see text] GeV and [Formula: see text].

The WD40-domain containing protein CORO2B is specifically enriched in glomerular podocytes and regulates the ventral actin cytoskeleton.

Podocytes are highly specialized epithelial cells essentially required to establish and maintain the kidney filtration barrier. Due to their complex cellular architecture these cells rely on an elaborated cytoskeletal apparatus providing plasticity as well as adaptive adhesion properties to withstand significant physical filtration forces. However, our knowledge about podocyte specific components of the cytoskeletal machinery is still incomplete.

Mutations in the X-linked cause a glycosylation disorder with autophagic defects.

The biogenesis of the multi-subunit vacuolar-type H-ATPase (V-ATPase) is initiated in the endoplasmic reticulum with the assembly of the proton pore V0, which is controlled by a group of assembly factors. Here, we identify two hemizygous missense mutations in the extracellular domain of the accessory V-ATPase subunit ATP6AP2 (also known as the [pro]renin receptor) responsible for a glycosylation disorder with liver disease, immunodeficiency, cutis laxa, and psychomotor impairment. We show that deficiency in the mouse liver caused hypoglycosylation of serum proteins and autophagy defects.

Purification and Identification of Membrane Proteins from Urinary Extracellular Vesicles using Triton X-114 Phase Partitioning.

Urinary extracellular vesicles (uEVs) have become a promising source for biomarkers accurately reflecting biochemical changes in kidney and urogenital diseases. Characteristically, uEVs are rich in membrane proteins associated with several cellular functions like adhesion, transport, and signaling. Hence, membrane proteins of uEVs should represent an exciting protein class with unique biological properties.

Fiducial, total and differential cross-section measurements of -channel single top-quark production in collisions at 8 TeV using data collected by the ATLAS detector.

Detailed measurements of -channel single top-quark production are presented. They use 20.2 fb[Formula: see text] of data collected by the ATLAS experiment in proton-proton collisions at a centre-of-mass energy of 8 TeV at the LHC.

Topological cell clustering in the ATLAS calorimeters and its performance in LHC Run 1.

The reconstruction of the signal from hadrons and jets emerging from the proton-proton collisions at the Large Hadron Collider (LHC) and entering the ATLAS calorimeters is based on a three-dimensional topological clustering of individual calorimeter cell signals. The cluster formation follows cell signal-significance patterns generated by electromagnetic and hadronic showers. In this, the clustering algorithm implicitly performs a topological noise suppression by removing cells with insignificant signals which are not in close proximity to cells with significant signals.

Measurements of electroweak [Formula: see text] production and constraints on anomalous gauge couplings with the ATLAS detector.

Measurements of the electroweak production of a boson in association with two jets at high dijet invariant mass are performed using [Formula: see text] 7 and 8 [Formula: see text] proton-proton collision data produced by the Large Hadron Collider, corresponding respectively to 4.7 and 20.2 fb[Formula: see text] of integrated luminosity collected by the ATLAS detector.

Jet reconstruction and performance using particle flow with the ATLAS Detector.

This paper describes the implementation and performance of a particle flow algorithm applied to 20.2 fb[Formula: see text] of ATLAS data from 8 TeV proton-proton collisions in Run 1 of the LHC. The algorithm removes calorimeter energy deposits due to charged hadrons from consideration during jet reconstruction, instead using measurements of their momenta from the inner tracker.

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton-proton collisions at the LHC.

This paper presents the method and performance of primary vertex reconstruction in proton-proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of [Formula: see text] TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy.

Performance of the ATLAS trigger system in 2015.

During 2015 the ATLAS experiment recorded [Formula: see text] of proton-proton collision data at a centre-of-mass energy of [Formula: see text]. The ATLAS trigger system is a crucial component of the experiment, responsible for selecting events of interest at a recording rate of approximately 1 kHz from up to 40 MHz of collisions. This paper presents a short overview of the changes to the trigger and data acquisition systems during the first long shutdown of the LHC and shows the performance of the trigger system and its components based on the 2015 proton-proton collision data.

Semifluorinated Alkane Eye Drops for Treatment of Dry Eye Disease Due to Meibomian Gland Disease.

Purpose: Meibomian gland disease is generally accepted as the leading cause for evaporative dry eye disease (DED). In a previous study, perfluorohexyloctane, a semifluorinated alkane, has been demonstrated to significantly increase tear film breakup time and to reduce corneal fluorescein staining in patients with evaporative DED, thereby vastly reducing dry eye-related symptoms. This study was set up to evaluate perfluorohexyloctane in a larger population of patients with Meibomian gland dysfunction.

Mitochondrial Priming by CD28.

T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand.

DNA strand breaks and TDP-43 mislocation are absent in the murine hSOD1G93A model of amyotrophic lateral sclerosis in vivo and in vitro.

Mutations in the human Cu/Zn superoxide dismutase type-1 (hSOD1) gene are common in familial amyotrophic lateral sclerosis (fALS). The pathophysiology has been linked to, e.g.