Novel approach to analysing large data sets of personal sun exposure measurements

Personal sun exposure measurements provide important information to guide the development of sun awareness and disease prevention campaigns. We assess the scaling properties of personal ultraviolet radiation (pUVR) sun exposure measurements using the wavelet transform (WT) spectral analysis to process long-range, high-frequency personal recordings collected by electronic UVR dosimeters designed to measure erythemal UVR exposure. We analysed the sun exposure recordings of school children, farmers, marathon runners and outdoor workers in South Africa, and construction workers and work site supervisors in New Zealand. We found scaling behaviour in all the analysed pUVR data sets. We found that the observed scaling changes from uncorrelated to long-range correlated with increasing duration of sun exposure. Peaks in the WT spectra that we found suggest the existence of characteristic times in sun exposure behaviour that were to some extent universal across our data set. Our study also showed that WT measures enable group classification, as well as distinction between individual UVR exposures, otherwise unattainable by conventional statistical methods

Mutations with pathogenic potential in proteins located in or at the composite junctions of the intercalated disk connecting mammalian cardiomyocytes: a reference thesaurus for arrhythmogenic cardiomyopathies and for Naxos and Carvajal diseases

In the past decade, an avalanche of findings and reports has correlated arrhythmogenic ventricular cardiomyopathies (ARVC) and Naxos and Carvajal diseases with certain mutations in protein constituents of the special junctions connecting the polar regions (intercalated disks) of mature mammalian cardiomyocytes. These molecules, apparently together with some specific cytoskeletal proteins, are components of (or interact with) composite junctions. Composite junctions contain the amalgamated fusion products of the molecules that, in other cell types and tissues, occur in distinct separate junctions, i.e. desmosomes and adherens junctions. As the pertinent literature is still in an expanding phase and is obviously becoming important for various groups of researchers in basic cell and molecular biology, developmental biology, histology, physiology, cardiology, pathology and genetics, the relevant references so far recognized have been collected and are presented here in the following order: desmocollin-2 (Dsc2, DSC2), desmoglein-2 (Dsg2, DSG2), desmoplakin (DP, DSP), plakoglobin (PG, JUP), plakophilin-2 (Pkp2, PKP2) and some non-desmosomal proteins such as transmembrane protein 43 (TMEM43), ryanodine receptor 2 (RYR2), desmin, lamins A and C, striatin, titin and transforming growth factor-β3 (TGFβ3), followed by a collection of animal models and of reviews, commentaries, collections and comparative studies

Generalized Disjunctive Programming: Solution Strategies

Generalized disjunctive programming (GDP) is an extension of the disjunctive programming paradigm developed by Balas. The GDP formulation involves Boolean and continuous variables that are specified in algebraic constraints, disjunctions and logic propositions, which is an alternative representation to the traditional algebraic mixed-integer programming formulation. GDP has proven to be very useful in representing a wide variety of problems successfully. Even though a wealth of powerful algorithms exist to solve these problems, GDP suffers a lack of mature solver technology. The main goal of this paper is to review the basic concepts and algorithms related to GDP problems and describe how solver technology is being developed. With this in mind after providing a brief review of MINLP optimization, we present an overview of GDP for the case of convex functions emphasizing the quality of continuous relaxations of alternative reformulations that include the big-M and the hull relaxation. We then review disjunctive branch and bound as well as logic-based decomposition methods that circumvent some of the limitations in traditional MINLP optimization. The first implemented GDP solver LogMIP successfully demonstrated that formulating and solving such problems can be done in an algebraic modeling system like GAMS. Recently, LogMIP has been introduced into GAMS’ Extended Mathematical Programming (EMP) framework integrating it much closer into the GAMS system and language and at the same time offering much more flexibility to the user. Since the model is separated from the reformulation chosen and from the solver used to solve the automatically generated model, this setup allows to easily switch methods at no costs and to benefit from advancing solver technology.Fil: Ruiz, Juan Pablo. University of Carnegie Mellon; Estados UnidosFil: Jagla, Jan H.. No especifíca;Fil: Grossmann, Ignacio E.. University of Carnegie Mellon; Estados UnidosFil: Meeraus, Alex. No especifíca;Fil: Vecchietti, Aldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo y Diseño. Universidad Tecnológica Nacional. Facultad Regional Santa Fe. Instituto de Desarrollo y Diseño; Argentin

Landscape of genetic lesions in 944 patients with myelodysplastic syndromes.

High-throughput DNA sequencing significantly contributed to diagnosis and prognostication in patients with myelodysplastic syndromes (MDS). We determined the biological and prognostic significance of genetic aberrations in MDS. In total, 944 patients with various MDS subtypes were screened for known/putative mutations/deletions in 104 genes using targeted deep sequencing and array-based genomic hybridization. In total, 845/944 patients (89.5%) harbored at least one mutation (median, 3 per patient; range, 0-12). Forty-seven genes were significantly mutated with TET2, SF3B1, ASXL1, SRSF2, DNMT3A, and RUNX1 mutated in >10% of cases. Many mutations were associated with higher risk groups and/or blast elevation. Survival was investigated in 875 patients. By univariate analysis, 25/48 genes (resulting from 47 genes tested significantly plus PRPF8) affected survival (P<0.05). The status of 14 genes combined with conventional factors revealed a novel prognostic model ('Model-1') separating patients into four risk groups ('low', 'intermediate', 'high', 'very high risk') with 3-year survival of 95.2, 69.3, 32.8, and 5.3% (P<0.001). Subsequently, a 'gene-only model' ('Model-2') was constructed based on 14 genes also yielding four significant risk groups (P<0.001). Both models were reproducible in the validation cohort (n=175 patients; P<0.001 each). Thus, large-scale genetic and molecular profiling of multiple target genes is invaluable for subclassification and prognostication in MDS patients

Molecular profiling of myeloid progenitor cells in multi-mutated advanced systemic mastocytosis identifies KIT D816V as a distinct and late event

To explore the molecular profile and its prognostic implication in systemic mastocytosis (SM), we analyzed the mutation status of granulocyte-macrophage colony-forming progenitor cells (CFU-GM) in patients with KIT D816V+ indolent systemic mastocytosis (ISM, n=4), smoldering SM (SSM, n=2), aggressive SM (ASM, n=1), SM with associated clonal hematologic non-mast cell lineage disorder (SM-AHNMD, n=5) and ASM-AHNMD (n=7). All patients with (A)SM-AHNMD (n=12) carried 1 to 4 (median 3) additional mutations in 11 genes tested, most frequently TET2, SRSF2, ASXL1, CBL and EZH2. In multi-mutated (A)SM-AHNMD, KIT D816V positive single-cell-derived CFU-GM colonies were identified in 8/12 patients (median 60%, range 0–95). Additional mutations were identified in CFU-GM colonies in all patients, and logical hierarchy analysis indicated that mutations in TET2, SRSF2 and ASXL1 preceded KIT D816V. In ISM/SSM, no additional mutations were detected and CFU-GM colonies were exclusively KIT D816V negative. These data indicate that (a) (A)SM-AHNMD is a multi-mutated neoplasm, (b) mutations in TET2, SRSF2 or ASXL1 precede KIT D816V in ASM-AHNMD, (c) KIT D816V is thus a phenotype-modifier towards SM and (d) KIT D816V or other mutations are rare in CFU-GM colonies of ISM/SSM patients which might explain at least in part their better prognosis