Search results for "Loss function"
showing 6 items of 46 documents
1H, 13C and 15N NMR chemical shift assignments of cAMP-regulated phosphoprotein-19 and -16 (ARPP-19 and ARPP-16)
2020
Protein Phosphatase 2A, PP2A, the principal Serine/threonine phosphatase, has major roles in broad range of signaling pathways that include regulation of cell cycle, cell proliferation and neuronal signaling. The loss of function of PP2A is linked with many human diseases, like cancer and neurodegenerative disorders. Protein phosphatase 2A (PP2A) functions as tumor suppressor and its tumor suppressor activity is inhibited by the overexpression of PP2A inhibitor proteins in most of the cancers. ARPP-19/ARPP-16 has been identified as one of the potential PP2A inhibitor proteins. Here, we report the resonance assignment of backbone 1H, 13C and 15N atoms of human ARPP-19 and ARPP-16 proteins. T…
LARP7 variants and further delineation of the Alazami syndrome phenotypic spectrum among primordial dwarfisms: 2 sisters.
2019
Abstract Alazami syndrome (AS) (MIM# 615071 ) is an autosomal recessive microcephalic primordial dwarfism (PD) with recognizable facial features and severe intellectual disability due to depletion or loss of function variants in LARP7. To date, 15 patients with AS have been reported. Here we describe two consanguineous Algerian sisters with Alazami PD due to LARP7 homozygous pathogenic variants detected by whole exome sequencing. By comparing these two additional cases with those previously reported, we strengthen the key features of AS: severe growth restriction, severe intellectual disability and some distinguishing facial features such as broad nose, malar hypoplasia, wide mouth, full li…
Conditional predictive inference for online surveillance of spatial disease incidence
2011
This paper deals with the development of statistical methodology for timely detection of incident disease clusters in space and time. The increasing availability of data on both the time and the location of events enables the construction of multivariate surveillance techniques, which may enhance the ability to detect localized clusters of disease relative to the surveillance of the overall count of disease cases across the entire study region. We introduce the surveillance conditional predictive ordinate as a general Bayesian model-based surveillance technique that allows us to detect small areas of increased disease incidence when spatial data are available. To address the problem of mult…
Progestogens and risk of breast cancer: a link between bone and breast?
2015
This article reviews the data supporting the role of receptor activator of the nuclear factor kappa (RANK) and its ligand, RANKL, in progestogen-induced breast cancer. Both experimental and clinical studies have been included. The expression of both RANK and RANKL has been described in epithelial cells of both mice and humans. Experiments of gain and loss of function in mice have shown that RANK/RANKL mediate alveologenesis during pregnancy or the estrous cycle. Moreover, the participation of the RANK/RANKL has been detected in models of breast carcinogenesis associated with progestogens-like medroxyprogesterone acetate. Recent clinical studies have found that the expression of RANK is asso…
RNA-mediated therapies in myotonic dystrophy
2018
Myotonic dystrophy 1 (DM1) is a multisystemic neuromuscular disease caused by a dominantly inherited 'CTG' repeat expansion in the gene encoding DM Protein Kinase (DMPK). The repeats are transcribed into mRNA, which forms hairpins and binds with high affinity to the Muscleblind-like (MBNL) family of proteins, sequestering them from their normal function. The loss of function of MBNL proteins causes numerous downstream effects, primarily the appearance of nuclear foci, mis-splicing, and ultimately myotonia and other clinical symptoms. Antisense and other RNA-mediated technologies have been applied to target toxic-repeat mRNA transcripts to restore MBNL protein function in DM1 models, such as…
A Multi-Objective Design Approach for the c Chart Considering Taguchi Loss Function
2014
The present paper proposes a multi-objective design approach for the c chart, considering in the optimization process of the chart parameters both the statistical and the economic objectives. In particular, the minimization of the hourly total quality related costs is the considered objective to carry out the economic goal, whereas the statistical objective is reached by the minimization the out-of-control average run length of the chart. A mixed integer non-linear constrained mathematical model is formulated to solve the treated multi-objective optimization problem, whereas the Pareto optimal frontier is described by the «-constraint method. In order to show the employment of the proposed …