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Quantitative proteomic analysis of microdissected breast cancer tissues : comparison of label-free and SILAC-based quantification with shotgun, directed, and targeted MS approaches

Quantitative proteomics plays an important role in validation of breast-cancer-related biomarkers. In this study, we systematically compared the performance of label-free quantification (LFQ) and SILAC with shotgun and directed methods for quantifying breast-cancer-related markers in microdissected tissues. We show that LFQ leads to slightly higher coefficient of variation (CV) for protein quantif

Proteogenomic Workflow Reveals Molecular Phenotypes Related to Breast Cancer Mammographic Appearance

Proteogenomic approaches have enabled the generat̲ion of novel information levels when compared to single omics studies although burdened by extensive experimental efforts. Here, we improved a data-independent acquisition mass spectrometry proteogenomic workflow to reveal distinct molecular features related to mammographic appearances in breast cancer. Our results reveal splicing processes detecta

Can trainees safely perform pancreatoenteric anastomosis? A systematic review, meta-analysis, and risk-adjusted analysis of postoperative pancreatic fistula

Background: The complexity of pancreaticoduodenectomy and fear of morbidity, particularly postoperative pancreatic fistula, can be a barrier to surgical trainees gaining operative experience. This meta-analysis sought to compare the postoperative pancreatic fistula rate after pancreatoenteric anastomosis by trainees or established surgeons. Methods: A systematic review of the literature was perfor

Transferability of tag SNPs in genetic association studies in multiple populations

A general question for linkage disequilibrium-based association studies is how power to detect an association is compromised when tag SNPs are chosen from data in one population sample and then deployed in another sample. Specifically, it is important to know how well tags picked from the HapMap DNA samples capture the variation in other samples. To address this, we collected dense data uniformly

Risk stratification in congestive heart failure patients using a model-based approach to heart rate turbulence characterization

Heart rate turbulence (HRT) is commonly assessed by two parameters: turbulence onset (TO) and turbulence slope (TS), both obtained by averaging RR tachograms following a ventricular premature beat (VPB). It has been recently shown that a model-based detection-theoretical approach results in HRT indices outperforming TO/TS in identifying the presence or absence of HRT. The aim of this work is to ev

Recommendations of the LHC Dark Matter Working Group : Comparing LHC searches for dark matter mediators in visible and invisible decay channels and calculations of the thermal relic density

Weakly-coupled TeV-scale particles may mediate the interactions between normal matter and dark matter. If so, the LHC would produce dark matter through these mediators, leading to the familiar “mono-X” search signatures, but the mediators would also produce signals without missing momentum via the same vertices involved in their production. This document from the LHC Dark Matter Working Group sugg

Modelling and optimisation in European Kidney Exchange Programmes

The complex multi-criteria optimisation problems arising in Kidney Exchange Programmes have received considerable attention both in practice and in the scientific literature. Whereas theoretical advancements are well reviewed and synthesised, this is not the case for practice. We present a synthesis of models and methods applied in present European Kidney Exchange Programmes, which is based on det

LUCAS versus manual chest compression during ambulance transport : A hemodynamic study in a porcine model of cardiac arrest

Background—Mechanical chest compression (CC) is currently suggested to deliver sustained high-quality CC in a moving ambulance. This study compared the hemodynamic support provided by a mechanical piston device or manual CC during ambulance transport in a porcine model of cardiopulmonary resuscitation. Methods and Results—In a simulated urban ambulance transport, 16 pigs in cardiac arrest were ra

Increased vimentin in human α- and β-cells in type 2 diabetes

Type 2 diabetes (T2DM) is associated with pancreatic islet dysfunction. Loss of β-cell identity has been implicated via dedifferentiation or conversion to other pancreatic endocrine cell types. How these transitions contribute to the onset and progression of T2DM in vivo is unknown. The aims of this study were to determine the degree of epithelial-to-mesenchymal transition occurring in α and β cel

Semiempirical breakdown curves of C2N(+) and C3N(+) molecules; application to products branching ratios predictions of physical and chemical processes involving these adducts

We constructed semiempirical breakdown curves (BDC) for C2N, C3N, C2N+ and C3N+ molecules. These BDC, which are energy dependent dissociation branching ratios (BR) curves, were used to predict products branching ratios for various processes leading to the formation of C2N(+) and C3N(+) excited adducts. These processes, of astrochemical interest, are neutral-neutral and ion-molecule reactions, diss

KRW composition theorems via lifting

One of the major open problems in complexity theory is proving super-logarithmic lower bounds on the depth of circuits (i.e., mathrm{P} nsubseteq text{NC}{1}). Karchmer, Raz, and Wigderson [13] suggested to approach this problem by proving that depth complexity behaves'as expected' with respect to the composition of functions f diamond g. They showed that the validity of this conjecture would impl

Mapping Resonance Structures in Transient Core-Ionized Atoms

The nature of transient electronic states created by photoabsorption critically determines the dynamics of the subsequently evolving system. Here, we investigate K-shell photoionized atomic neon by absorbing a second photon within the Auger-decay lifetime of 2.4 fs using the European XFEL, a unique high-repetition-rate, wavelength-tunable x-ray free-electron laser. By high-resolution electron spec

A systemic overreaction to years versus decades of warming in a subarctic grassland ecosystem

Temperature governs most biotic processes, yet we know little about how warming affects whole ecosystems. Here we examined the responses of 128 components of a subarctic grassland to either 5–8 or >50 years of soil warming. Warming of >50 years drove the ecosystem to a new steady state possessing a distinct biotic composition and reduced species richness, biomass and soil organic matter. However,

The GALAH survey : Chemical homogeneity of the Orion complex

Due to its proximity, the Orion star forming region is often used as a proxy to study processes related to star formation and to observe young stars in the environment they were born in. With the release of Gaia DR2, the distance measurements to the Orion complex are now good enough that the 3D structure of the complex can be explored. Here we test the hypothesis that, due to non-trivial structure

Hybrid speciation driven by multilocus introgression of ecological traits

Hybridization allows adaptations to be shared among lineages and may trigger the evolution of new species1,2. However, convincing examples of homoploid hybrid speciation remain rare because it is challenging to demonstrate that hybridization was crucial in generating reproductive isolation3. Here we combine population genomic analysis with quantitative trait locus mapping of species-specific trait

Myeloid CD40 deficiency reduces atherosclerosis by impairing macrophages’ transition into a pro-inflammatory state

Aims CD40 and its ligand, CD40L, play a critical role in driving atherosclerotic plaque development. Disrupted CD40-signalling reduces experimental atherosclerosis and induces a favourable stable plaque phenotype. We recently showed that small molecule-based inhibition of CD40-tumour necrosis factor receptor associated factor-6 interactions attenuates atherosclerosis in hyperlipidaemic mice via ma

Tau-neurodegeneration mismatch reveals vulnerability and resilience to comorbidities in Alzheimer's continuum

INTRODUCTION: Variability in relationship of tau-based neurofibrillary tangles (T) and neurodegeneration (N) in Alzheimer's disease (AD) arises from non-specific nature of N, modulated by non-AD co-pathologies, age-related changes, and resilience factors. METHODS: We used regional T-N residual patterns to partition 184 patients within the Alzheimer's continuum into data-driven groups. These were c

Proteomic profiling reveals that ESR1 mutations enhance cyclin-dependent kinase signaling

Three quarters of all breast cancers express the estrogen receptor (ER, ESR1 gene), which promotes tumor growth and constitutes a direct target for endocrine therapies. ESR1 mutations have been implicated in therapy resistance in metastatic breast cancer, in particular to aromatase inhibitors. ESR1 mutations promote constitutive ER activity and affect other signaling pathways, allowing cancer cell

Sex-Differences in Alpha-1 Antitrypsin Deficiency : Data From the EARCO Registry

Background: Sex and gender influence many aspects of chronic obstructive pulmonary disease (COPD). Limited data are available on this topic in alpha-1 antitrypsin deficiency (AATD). We therefore aimed to investigate sex issues in the EARCO registry, a prospective, international, observational cohort study. Methods: Baseline data from PiZZ individuals, enrolled in the registry with complete data on