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BACKGROUND: CaSR gene is a candidate for calcium nephrolithiasis. Single-nucleotide polymorphisms (SNPs) encompassing its regulatory region were associated with calcium nephrolithiasis. AIMS: We tested SNPs in the CaSR gene regulatory region associated with calcium nephrolithiasis and their effects in kidney. SUBJECTS AND METHODS: One hundred sixty-seven idiopathic calcium stone formers and 214 healthy controls were genotyped for four CaSR gene SNPs identified by bioinformatics analysis as modifying transcription factor binding sites. Strontium excretion after an oral load was tested in 55 stone formers. Transcriptional activity induced by variant alleles at CaSR gene promoters was compared by luciferase reporter gene assay in HEK-293 and HKC-8 cells. CaSR and claudin-14 mRNA levels were measured by real-time PCR in 107 normal kidney medulla samples and compared in patients with different CaSR genotype. RESULTS: Only rs6776158 (A>G), located in the promoter 1, was associated with nephrolithiasis. Its minor G allele was more frequent in stone formers than controls (37.8% vs 26.4%, P = .001). A reduced strontium excretion was observed in GG homozygous stone formers. Luciferase fluorescent activity was lower in cells transfected with the promoter 1 including G allele at rs6776158 than cells transfected with the A allele. CaSR mRNA levels were lower in kidney medulla samples from homozygous carriers for the G allele at rs6776158 than carriers for the A allele. Claudin-14 mRNA levels were also lower in GG homozygous subjects. CONCLUSIONS: Minor allele at rs6776158 may predispose to calcium stones by decreasing transcriptional activity of the CaSR gene promoter 1 and CaSR expression in kidney tubules.

Stato dell'arte sulle tecniche di analisi di difetti in materiali compositi

Tecniche di registrazione di nuvole di punti per il confronto di modelli di scene indoor

BACKGROUND: Calcium-sensing receptor gene (CaSR) is a candidate to explain susceptibility to calcium kidney stones. Thus, we studied CaSR gene single-nucleotide polymorphisms (SNPs) and haplotypes associated with stones. METHODS: Four hundred and sixty-three calcium stone formers and 213 healthy controls were genotyped for 21 SNPs mapping the whole CaSR gene. CaSR gene structure was studied. SNPs and haplotypes were analysed for association with stones. RESULTS: Three haplotype blocks were identified in the CaSR gene. The first block was characterized by six SNPs and included gene promoters. The rs7652589 and rs1501899 SNPs and the CATTCA haplotype of the first block were significantly more frequent in normocitraturic calcium kidney stone formers than controls. The risk of stones was increased in normocitraturic homozygous patients and heterozygotes for the CATTCA haplotype. The rate of stones was higher in stone formers with the CATTCA haplotype. In a three-generation family, calcium stones were associated with the CATTCA haplotype. The bioinformatic analysis identified a new site for the octamer-binding transcription factor 1 in the presence of the variant alleles at the rs7652589 and rs1501899 SNPs. This transcription factor may downregulate the transcription of vitamin D-dependent genes and the CaSR expression. Conclusion. SNPs and CATTCA haplotype of the CaSR gene first block is associated with kidney stones in normocitraturic patients.

Prendendo spunto dalla pubblicazione della nuova edizione della norma ISO 4498,sono qui riassunte le indicazioni essenziali per una corretta esecuzione delle prove di macroe microdurezza sui componenti sinterizzati metallici e sui metalli duri, ed è ampiamente commentatala loro interpretazione, tenuto conto che la struttura di questi materiali presenta aspetti talmentepeculiari da aver richiesto la stesura di norme apposite, che sono pertanto richiamate nella bibliografiainsieme con quelle di carattere generale.In particolare lo scopo è quello di fornire elementi per una corretta impostazione dell’assicurazionequalità in campo industriale: in questo modo si può instaurare tra fornitore ed utilizzatore un rapportoi cui termini siano reciprocamente accettabili, senza equivoci.

Most of the work in multiple model adaptive control with various forms of switching focused on continuous-time systems. The purpose of this technical note is to extend the results of one approach, the adaptive mixing control (AMC), to discrete-time systems. Further, the technical note solves the tracking problem which has not been addressed in most schemes of this class. Stability and robustness properties of the AMC scheme for discrete-time systems are analyzed. It is shown that in the ideal case, when no disturbances or unmodeled dynamics are present, the tracking error converges to zero. In the non ideal case, the mean-square tracking error is of the order of magnitude of the modeling error provided the unmodeled dynamics satisfy a norm-bound condition. While these robustness results are conceptually similar to those of traditional robust adaptive control, the proposed scheme does not suffer from the drawback of stabilizability of the estimated plant and in addition performs much better in simulation studies. Furthermore, it allows well developed results from robust control to be incorporated in the design. © 2011 IEEE. 57 4 1040 1045 Cited By :20

Calcium ions coordinate multiple cellular functions, among which the release of neurotransmitters, the gene expression, the regulation of inflammatory processes and the activation of apoptosis. The regulation of calcium metabolism involves several biochemical pathways, different sub-cellular compartments and it is strongly compromised during aging. In fact, alterations of the calcium signalling process are frequent in the neurodegenerative diseases and mainly result in the hyper-activation of the apoptotic process. To investigate molecular alterations occurring in neurodegenerative diseases, an integrative mathematical model designed to represent the calcium metabolism has been defined. The model, which is mathematically defined by ODEs system, reproduces the calcium ions functions during glutamate stimulation. In particular, a number of different situations, such as (i) the glutamatergic transmission using different impulse frequencies, (ii) the comparison between normal and excessive stimulation and (iii) the calcium homeostasis in young/aging neurons have been reproduced. In particular, the simulations of several features associated to neurodegenerative disease, especially at molecular level and with a particular focus on the apoptotic process, allow highlighting the differences occurring in calcium metabolism in normal and pathological states. Furthermore collecting the achieved simulation and sensitivity analysis results, we propose an in silico strategy for preventing the activation of the apoptotic pathway in the neurodegenerative diseases.

Cancer cells differ from their normal counterparts more in terms of regulatory networks than of specific molecules. A recently recognized hallmark of cancer is the increased uptake of nutrients, particularly glucose, associated with a higher lactate pro- duction. A common step of tumorigenesis, which influences these metabolic alterations, is the constitutive activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Fol- lowing an integrative systems biology approach, we propose a model for the in silico investigation of the PI3K/Akt pathway effects on the central metabolism. This model represents a useful tool for the computational analysis of the metabolic differences be- tween normal and pathological conditions.

Several classes of identifier and non-identifier based adaptive control schemes using a supervisory switching logic have been proposed in the literature. These schemes are based on different assumptions and claim to guarantee certain stability and performance properties. The purpose of this paper is to clarify what each algorithm guarantess in theory and how it performs in simulations. The identifier based schemes: Robust Multiple Model Adaptive Control (RMMAC) and Adaptive Mixing Control (AMC) and the non-identifier based schemes: Unfalsified Adaptive Switching Control (UASC) and Multi-model Unfalsified Adaptive Switching Control (MUASC). For each scheme we present the basic features of the algorithm and state the stability and performance guaranteed in theory. The benchmark example of [1] is used to test the stability and performance properties of the schemes considered using extensive simulations. Our results show that the identifier based schemes require some knowledge about the plant whereas the non identifier based do not. The identifier based schemes however typically perform better than non-identifier based schemes when all the plant assumptions are satisfied, and can guarantee, from a theory viewpoint, at least for the AMC scheme, transient and asymptotic performance. The main positive feature the UASC and MUASC schemes is that, even in the absence of any prior information on the uncertain plant, they can select in finite time a final controller yielding, a finite affine gain from the reference to the data, under the minimal conceivable requirement, viz. the existence of a stabilizing candidate controller in the candidate controller set. ©2010 IEEE. Sponsors: Cyprus University of Technology University of Cyprus Conference code: 80672 Cited By :4

Due to the lack of experimental measurements, biological variability and experimental errors, the value of many parameters of the systems biology mathematical models is yet unknown or uncertain. A possible computational solution is the parameter estimation, that is the identification of the parameter values that determine the best model fitting respect to experimental data. We have developed an experiment to distribute each run of the parameter estimation algorithm on a different computational resource. The key feature of the implementation is a relational database that allows the user to swap the candidate solutions among the working nodes during the computations. The comparison of the distributed implementation with the parallel one showed that the presented approach enables a faster and better estimation of systems biology models.