Context Dependence, MOPs,WHIMs and procedures Recanati and Kaplan on Cognitive Aspects in Semantics

After presenting Kripke’s criticism to Frege’s ideas on context dependence of thoughts, I present two recent attempts of considering cognitive aspects of context dependent expressions inside a truth conditional pragmatics or semantics: Recanati’s non-descriptive modes of presentation (MOPs) and Kaplan’s ways of having in mind (WHIMs). After analysing the two attempts and verifying which answers they should give to the problem discussed by Kripke, I suggest a possible interpretation of these attempts: to insert a procedural or algorithmic level in semantic representations of indexicals. That a function may be computed by different procedures might suggest new possibilities of integrating contextual cognitive aspects in model theoretic semanti

5.11 'Raffaello Project': Application of the 'Disease and Care Management' Approach in Cardiovascular Disease Prevention

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Influence of residual perfusion within the infarct zone on the natural history of left ventricular dysfunction after acute myocardial infarction.

This study used myocardial contrast echocardiography to investigate the extent of residual perfusion within the infarct zone in a select group of patients with recently reperfused myocardial infarction and evaluated its influence on the ultimate infarct size. BACKGROUND: Limited information is available on the status of myocardial perfusion within postischemic dysfunctional segments at predischarge and on its influence on late regional and global functional recovery. METHODS: Twenty patients with acute myocardial infarction were selected for the study. Patients met the following inclusion criteria: 1) single-vessel coronary artery disease; 2) patency of infarct-related artery with persistent postischemic dysfunctional segments at predischarge; 3) stable clinical condition up to 6 months after hospital discharge. All selected patients underwent coronary angiography and myocardial contrast echocardiography before hospital discharge and repeated the echocardiographic examination 6 months later. Patients were grouped according to the pattern of contrast enhancement in predischarge dysfunctional segments. RESULTS: In nine patients (group I), the length of segments showing abnormal contraction coincided with that of the contrast defect segments. In the remaining 11 patients (group II), postischemic dysfunctional segments were partly or completely reperfused. There was no difference between the two groups in asynergic segment length at predischarge (7.3 +/- 2.5 vs. 7.2 +/- 4.3 cm, p = NS). At follow-up study, asynergic segment length was significantly reduced in group II patients, whereas no changes were observed in group I patients (from 7.2 +/- 4.3 to 4.7 +/- 3.7 cm, p < 0.005; and from 7.3 +/- 2.5 to 7.5 +/- 2.9 cm, p = NS, respectively). CONCLUSIONS: Among patients with a predischarge patent infarct-related artery, further improvement in regional and global function may be expected during follow-up when residual perfusion in the infarct zone is present

Different gene expression modulation is the major effect fue to shear stress and stent application in huvecs model: preliminary results

Although it is known that disturbed shear stress may cause endothelial damage, the mechanism by which a stent procedure may affect the endothelium is not yet fully clarify. We present the preliminary data on gene expression analysis of human endothelial cells in a laminar flow bioreactor (LFB) system submitted to different physical (flow changes) and/or mechanical (stent application) stimuli. Our preliminary results show that low shear stress together with stent procedure are the experimental conditions that mainly modulate the highest number of genes in human endothelial model. Those genes belong to pathways specifically involved in the endothelial dysfunctio

Genetic pre-participation screening in selected athletes: a new tool for the prevention of sudden cardiac death?

Sudden cardiac death (SCD) of athletes is a topical issue. “Borderline cardiac abnormalities”, which occur in ~2% of elite male athletes, may result in SCD, which may have a genetic base. Genetic analysis may help identify pathological cardiac abnormalities. We performed phenotype-guided genetic analysis in athletes who, pre-participation, showed ECG and/or echo “borderline” abnormalities, to discriminate subjects at a greater risk of SCD. Methods: We studied 24 elite athletes referred by the National Federation of Olympic sports; and 25 subjects seeking eligibility to practice agonistic sport referred by the Osservatorio Epidemiologico della Medicina dello Sport della Regione Campania. Inclusion criteria: a) ECG repolarization borderline abnormalities; b) benign ventricular arrhythmias; c) left ventricular wall thickness in the grey zone of physiology versus pathology (max wall thickness 12-15 mm in females; 13-16 mm in males). Based on the suspected phenotype, we screened subjects for the LMNA gene, for 8 sarcomeric genes, 5 desmosomal genes, and cardiac calcium, sodium and potassium channel disease genes. Results: Genetic analysis was completed in 37/49 athletes, 22 competitive and 27 non-competitive athletes, showing “borderline” clinical markers suggestive of hypertrophic cardiomyopathy (HCM,n. 24), dilated cardiomyopathy (n. 4), arrhythmogenic right ventricular dysplasia/cathecholaminergic polymorphic ventricular tachycardia (ARVD/CPVT, n. 11), long QT syndrome (LQTS, n. 4), sick sinus syndrome (SSS, n. 5), Brugada syndrome (BrS, n. 1). We identifyed 11 mutations in 9 athletes (an ARVD athlete was compound heterozygote for the PKP2 gene and an HCM athlete was double heterozygote for the MYBPC3 and TNNT2 genes): 3 known mutations related to LQTS, HCM and ARVD, respectively, and 8 novel mutations, located in the SCN5A, RyR2, PKP2, MYBPC3 and ACTC1 genes. The new mutations were absent in ~800 normal chromosomes and were predicted “probably damaging” by in silico analysis. Patch clamp analysis in channelopathies indicated for some mutation abnormal biophysical behavior of the corresponding mutant protein. Conclusion: Genetic analysis may help distinguish between physiology and pathology in athletes with clinically suspected heart disease

Full-length TDP-43 and its C-terminal domain form filamentsin vitrohaving non-amyloid properties

Accumulation of ubiquitin-positive, tau- and α-synuclein-negative intracellular inclusions of TDP-43 in the central nervous system represents the major hallmark correlated to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Such inclusions have variably been described as amorphous aggregates or more structured deposits having amyloid properties. Here we have purified full-length TDP-43 (FL TDP-43) and its C-terminal domain (Ct TDP-43) to investigate the morphological, structural and tinctorial features of aggregates formed in vitro by them at pH 7.4 and 37 °C. AFM images indicate that both protein variants show a tendency to form filaments. Moreover, we show that both FL TDP-43 and Ct TDP-43 filaments possess a largely disordered secondary structure, as ascertained by far-UV circular dichroism and Fourier transform infra-red spectroscopy, do not bind Congo red and induce a very weak increase of thioflavin T fluorescence, indicating the absence of a clear amyloid-like signature

Where does Cosmological Perturbation Theory Break Down?

We apply the effective field theory approach to the coupled metric-inflaton system, in order to investigate the impact of higher dimension operators on the spectrum of scalar and tensor perturbations in the short-wavelength regime. In both cases, effective corrections at tree-level become important when the Hubble parameter is of the order of the Planck mass, or when the physical wave number of a cosmological perturbation mode approaches the square of the Planck mass divided by the Hubble constant. Thus, the cut-off length below which conventional cosmological perturbation theory does not apply is likely to be much smaller than the Planck length. This has implications for the observability of "trans-Planckian" effects in the spectrum of primordial perturbations.Comment: 25 pages, uses FeynM

7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors

7-Azaindole-1-carboxamides were designed as a new class of PARP-1 inhibitors. The compounds displayed a variable pattern of target inhibition profile that, in part, paralleled the antiproliferative activity in cell lines characterized by homologous recombination defects. A selected compound (1l; ST7710AA1) showed significant in vitro target inhibition and capability to substantially bypass the multidrug resistance mediated by Pgp. In antitumor activity studies against the MX1 human breast carcinoma growth in nude mice, the compound exhibited an effect similar to that of Olaparib in terms of tumor volume inhibition when used at a lower dose than the reference compound. Treatment was well tolerated, as no deaths or significant weight losses were observed among the treated animals

Polymorphisms in folate-metabolizing genes, chromosome damage, and risk of Down syndrome in Italian women: identification of key factors using artificial neural networks

<p>Abstract</p> <p>Background</p> <p>Studies in mothers of Down syndrome individuals (MDS) point to a role for polymorphisms in folate metabolic genes in increasing chromosome damage and maternal risk for a Down syndrome (DS) pregnancy, suggesting complex gene-gene interactions. This study aimed to analyze a dataset of genetic and cytogenetic data in an Italian group of MDS and mothers of healthy children (control mothers) to assess the predictive capacity of artificial neural networks assembled in TWIST system in distinguish consistently these two different conditions and to identify the variables expressing the maximal amount of relevant information to the condition of being mother of a DS child.</p> <p>The dataset consisted of the following variables: the frequency of chromosome damage in peripheral lymphocytes (BNMN frequency) and the genotype for 7 common polymorphisms in folate metabolic genes (<it>MTHFR </it>677C>T and 1298A>C, <it>MTRR </it>66A>G, <it>MTR </it>2756A>G, <it>RFC1 </it>80G>A and <it>TYMS </it>28bp repeats and 1494 6bp deletion). Data were analysed using TWIST system in combination with supervised artificial neural networks, and a semantic connectivity map.</p> <p>Results</p> <p>TWIST system selected 6 variables (BNMN frequency, <it>MTHFR </it>677TT, <it>RFC1 </it>80AA, <it>TYMS </it>1494 6bp +/+, <it>TYMS </it>28bp 3R/3R and <it>MTR </it>2756AA genotypes) that were subsequently used to discriminate between MDS and control mothers with 90% accuracy. The semantic connectivity map provided important information on the complex biological connections between the studied variables and the two conditions (being MDS or control mother).</p> <p>Conclusions</p> <p>Overall, the study suggests a link between polymorphisms in folate metabolic genes and DS risk in Italian women.</p

New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background

<p>Abstract</p> <p>Background</p> <p>Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS) have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis</p> <p>Results</p> <p>Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31%) and from 69.1 to 86.2% (average 76.6%) respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%). This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg158cys; hepatic lipase -480 C/T; endothelial nitric oxide synthase 690 C/T and glu298asp; vitamin K-dependent coagulation factor seven arg353glu, glycoprotein Ia/IIa 873 G/A and E-selectin ser128arg.</p> <p>Conclusion</p> <p>This study provides an alternative and reliable method to approach complex diseases. Indeed, the application of a novel artificial intelligence-based method offers a new insight into genetic markers of sporadic ALS pointing out the existence of a strong genetic background.</p