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Multiple mechanisms of MYCN dysregulation in Wilms tumour.

Genomic gain of the proto-oncogene transcription factor gene MYCN is associated with poor prognosis in several childhood cancers. Here we present a comprehensive copy number analysis of MYCN in Wilms tumour (WT), demonstrating that gain of this gene is associated with anaplasia and with poorer relapse-free and overall survival, independent of histology. Using whole exome and gene-specific sequenci

Unveiling Nanometer Scale Extinction and Scattering Phenomena through Combined Electron Energy Loss Spectroscopy and Cathodoluminescence Measurements

Plasmon modes of the exact same individual gold nanoprisms are investigated through combined nanometer-resolved electron energy-loss spectroscopy (EELS) and cathodoluminescence (CL) measurements. We show that CL only probes the radiative modes, in contrast to EELS, which additionally reveals dark modes. The combination of both techniques on the same particles thus provides complementary informatio

Advanced Intercross Line Mapping Suggests That Ncf1 (Ean6) Regulates Severity in an Animal Model of Guillain-Barre Syndrome

We here present the first genetic fine mapping of experimental autoimmune neuritis (EAN), the animal model of Guillain-Barre syndrome, in a rat advanced intercross line. We identified and refined a total of five quantitative trait loci on rat chromosomes 4, 10, and 12 (RNO4, RNO10, RNO12), showing linkage to splenic IFN-gamma secretion and disease severity. All quantitative trait loci were shared

Intradermal Delivery of TLR Agonists in a Human Explant Skin Model: Preferential Activation of Migratory Dendritic Cells by Polyribosinic-Polyribocytidylic Acid and Peptidoglycans

TLR agonists are attractive candidate adjuvants for therapeutic cancer vaccines as they can induce a balanced humoral and T cell-mediated immune response. With a dense network of dendritic cells (DCs) and draining lymphatics, the skin provides an ideal portal for vaccine delivery. Beside direct DC activation, TLR agonists may also induce DC activation through triggering the release of inflammatory

Effect on Survival and Hospitalization of Initiating Treatment for Chronic Heart Failure With Bisoprolol Followed by Enalapril, as Compared With the Opposite Sequence. Results of the Randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III.

Background - In patients with chronic heart failure (CHF), a beta-blocker is generally added to a regimen containing an angiotensin-converting-enzyme ( ACE) inhibitor. It is unknown whether beta-blockade as initial therapy may be as useful. Methods and Results - We randomized 1010 patients with mild to moderate CHF and left ventricular ejection fraction <= 35%, who were not receiving ACE inhibitor

The London Classification of gastrointestinal neuromuscular pathology: report on behalf of the Gastro 2009 International Working Group

Objective Guidelines on histopathological techniques and reporting for adult and paediatric gastrointestinal neuromuscular pathology have been produced recently by an international working group (IWG). These addressed the important but relatively neglected areas of histopathological practice of the general pathologist, including suction rectal biopsy and full-thickness intestinal tissue. Recommend

Providing rapid feedback in generated modular language environments adding error recovery to scannerless generalized-LR parsing

Integrated development environments (IDEs) increase programmer productivity, providing rapid, interactive feedback based on the syntax and semantics of a language. A heavy burden lies on developers of new languages to provide adequate IDE support. Code generation techniques provide a viable, efficient approach to semi-automatically produce IDE plugins. Key components for the realization of plugins

Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder: Which Patients Benefit from the Instillation?

The European Association of Urology non-muscle-invasive bladder cancer (NMIBC) guidelines recommend that all low- and intermediate-risk patients receive a single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB), but its use remains controversial.

GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma.

Glutamate receptors are well-known actors in the central and peripheral nervous systems, and altered glutamate signaling is implicated in several neurological and psychiatric disorders. It is increasingly recognized that such receptors may also have a role in tumor growth. Here we provide direct evidence of aberrant glutamate signaling in the development of a locally aggressive bone tumor, chondro

Copy Number Defects of G1-Cell Cycle Genes in Neuroblastoma are Frequent and Correlate with High Expression of E2F Target Genes and a Poor Prognosis

The tightly controlled network of cell cycle genes consists of a core of cyclin dependent kinases (CDKs) that are activated by periodically expressed cyclins. The activity of the cyclin-CDK complexes is regulated by cyclin dependent kinase inhibitors (CDKIs) and multiple signal transduction routes that converge on the cell cycle. Neuroblastoma are pediatric tumors that belong to the group of small

Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation

In development, epigenetic mechanisms such as DNA methylation have been suggested to provide a cellular memory to maintain multipotency but also stabilize cell fate decisions and direct lineage restriction. In this study, we set out to characterize changes in DNA methylation and gene expression during granulopoiesis using 4 distinct cell populations ranging from the oligopotent common myeloid prog

A car-seat example of automated anthropomorphic testing of fabrics using force-controlled robot motions

For the last years, automation is widely used to relieve humans from repetitive tasks, primarily and firstly within manufacturing. However, for products with less ideal (or hard to model) properties, and when forces depends on human interaction, automated testing has not been explored until now. This work presents the analysis of the (human-dependent) motions/forces based on a fully implemented te

Investigation by Combined Solid-State NMR and SAXS Methods of the Morphology and Domain Size in Polystyrene-b-Polyethylene Oxide-b-Polystyrene Triblock Copolymers

The microphase structure of a series of polystyrene-b-polyethylene oxide-b-polystyrene (SEOS) triblock copolymers with different compositions and molecular weights has been studied by solid-state NMR, DSC, wide and small angle X-ray scattering (WAXS and SAXS). WAXS and DSC measurements were used to detect the presence of crystalline domains of polyethylene-oxide (PEO) blocks at room temperature as

The Role of the ECG in Diagnosis, Risk Estimation, and Catheterization Laboratory Activation in Patients with Acute Coronary Syndromes: A Consensus Document

The electrocardiogram (ECG) is the most widely used imaging tool helping in diagnosis and initial management of patients presenting with symptoms compatible with acute coronary syndrome. Acute ischemia affects the configuration of the QRS complexes, the ST segments and the T waves. The ECG should be read along with the clinical assessment of the patient. ST segment elevation (and ST depression in

Effect of 3,4-Methylenedioxyamphetamine on Dendritic Spines Dynamics in Rat Neocortical Neurons - Involvement of Heat Shock Protein 27.

Along with chronic neurotoxic effects, the long-term consumption of amphetamines has been associated to psychiatric symptoms and memory disturbances. Dendritic spine dynamics have been discussed as a possible morphological correlate. However, the underlying mechanisms are still elusive. 3,4-Methylenedioxyamphetamine (MDA), a major drug of abuse and a main metabolite after 3,4-methylenedioxymethamp

Electrocardiographic classification of acute coronary syndromes: a review by a committee of the International Society for Holter and Non-Invasive Electrocardiology

The electrocardiogram (ECG) remains the most immediately accessible and widely used diagnostic tool for guiding emergency treatment strategies. The ECG recorded during acute myocardial ischemia is of diagnostic, therapeutic, and prognostic significance. In patients with myocardial ischemia as a result of decreased blood supply, the initial 12-lead ECG typically shows (1) predominant ST-segment ele

Evidence for isovector neutron-proton pairing from high-spin states in N=Z Rb-74

High-spin states in the odd-odd N=Z nucleus Rb-74(37)37 were studied using the Ca-40(Ca-40,alphanp) reaction. A previously observed odd-spin T=0 band has been extended to I-pi=(31(+)) and an even-spin T=0 band has been observed for the first time to I-pi=(22(+)); both have a pi(g(9/2))circle timesnu(g(9/2)) structure. A strongly coupled low-spin T=0,K=3 band has been interpreted as being based upo

Study of the role of functional variants of SLC22A4, RUNX1 and SUMO4 in systemic lupus erythematosus

Background: Functional polymorphisms of the solute carrier family 22, member 4 (SLC22A4), runt related transcription factor 1 (RUNX1) and small ubiquitin- like modifier 4 (SUMO4) genes have been shown to be associated with several autoimmune diseases. Objective: To test the possible role of these variants in susceptibility to or severity of systemic lupus erythematosus (SLE), on the basis that com