Metabolite accumulation in lysosomal storage disorders (LSDs) results in impaired cell function and multi-systemic disease. Although substrate reduction and lysosomal overload-decreasing therapies can ameliorate disease progression, the significance of lysosomal overload-independent mechanisms in the development of cellular dysfunction is unknown for most LSDs. Here, we identify a mechanism of ...

BACKGROUND Chronic metabolic acidosis (CMA) in normal adults results in complex endocrine and metabolic alterations including growth hormone (GH) insensitivity, hypothyroidism, hyperglucocorticoidism, hypoalbuminaemia and loss of protein stores. Similar alterations occur in chronic renal failure, a prototypical state of CMA. We evaluated whether metabolic acidosis contributes to the endocrine a...

The well-known Covariance Matrix Adaptation Evolution Strategy (CMA-ES) is a robust stochastic search algorithm for optimizing functions defined on a continuous search space R. Recently, mirrored samples and sequential selection have been introduced within CMA-ES to improve its local search performances. In this paper, we benchmark the (1,4m)-CMA-ES which implements mirrored samples and sequent...

Cow's milk allergy (CMA) is a complex disorder. Numerous milk proteins have been implicated in allergic responses and most of these have been shown to contain multiple allergenic epitopes. There is considerable heterogeneity amongst allergic individuals for the particular proteins and epitopes to which they react, and to further complicate matters, allergic reactions to cow's milk are driven by...

We have investigated the effects of Concanamycin A (CMA), a specific inhibitor of vacuolar type H(+)-ATPases, on acidification and function of the endo-lysosomal and contractile vacuole (CV) systems of D. discoideum. This drug inhibited acidification and increased the pH of endo-lysosomal vesicles both in vivo and in vitro in a dose dependent manner. Treatment also inhibited endocytosis and exo...

Colonie mucoprotein antigen (CMA), a high-molecularweight, tissue-specific mucin, was obtained from 9 normal mucosa! samples and 12 colonie adenocarcinomas. Puri fication was achieved by means of phenokwater extrac tion followed by ethanol precipitation and molecular sieve chromatography. Chemical analyses of the individual nor mal CMA preparations indicated similar qualitative and quantitative...

INTRODUCTION The aim of the study was to assess the use of faecal calprotectin (FCP) in infants with signs and symptoms of non-IgE-mediated cow's milk protein allergy (CMA) for both diagnosis and prediction of clinical response at the time of withdrawal of milk proteins. PATIENTS AND METHODS A one year prospective study was conducted on 82 infants between 1 and 12 months of age in the Eastern...

The covariance matrix adaptation evolution strategy (CMA-ES) is an efficient derivativefree optimization algorithm. It optimizes a black-box objective function over a well defined parameter space. In some problems, such parameter spaces are defined using function approximation in which feature functions are manually defined. Therefore, the performance of those techniques strongly depends on the...