Cataract and optic disk drusen in a patient with glycogenosis and di George syndrome: clinical and molecular report

Background We report the ophthalmic findings of a patient with type Ia glycogen storage disease (GSD Ia), DiGeorge syndrome (DGS), cataract and optic nerve head drusen (ONHD). Case presentation A 26-year-old white woman, born at term by natural delivery presented with a post-natal diagnosis of GSD Ia. Genetic testing by array-comparative genomic hybridization (CGH) for DGS was required because of her low levels of serum calcium. The patient has been followed from birth, attending the day-hospital every six months at the San Paolo Hospital, Milan, outpatient clinic for metabolic diseases and previously at another eye center. During the last day-hospital visit, a complete eye examination showed ONHD and cataract in both eyes. Next Generation Sequencing (NGS) was subsequently done to check for any association between the eye problems and metabolic aspects. Conclusions This is the first description of ocular changes in a patient with GSD Ia and DGS. Mutations explaining GSD Ia and DGS were found but no specific causative mutation for cataract and ONHD. The metabolic etiology of her lens changes is known, whereas the pathogenesis of ONHD is not clear. Although the presence of cataract and ONHD could be a coincidence; the case reported could suggest that hypocalcemia due to DGS could be the common biochemical pathway

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

Modulation of CYP1A1 by PKC Inhibitors and TPA Pre-Treatments in MH1C1 Rat Hepatoma Cells Exposed to 3 -Methylcholanthrene

Cytochrome P4501A1 (CYP1A1), an enzyme known to metabolize polycyclic aromatic hydrocarbons, is regulated by the aryl hydrocarbon receptor (AhR). The involvement of protein kinase C (PKC) in the regulation of AhR signal transduction pathway, has been widely studied but the role of specific PKC isoform(s) involved in this process it is not well clarified. To study which PKC isoform(s) is implicated in the regulation of CYP1A1, in the poorly tumorigenic MH1C1 rat hepatoma cells, we examined the effects of some PKC pharmacological inhibitors, Calphostin C (CAL), Staurosporine (STA) and H7, and of 12-0-tetradecanoyl phorbol 13-acetate (TPA), a PKC activator, on basal and 3- methylcholanthrene (MC)-induced CYP1A1 protein expression and mediated ethoxyresorufin O-deethylation (EROD) activity. In parallel, the activities of PKC-α, -βI, -δ and -ε isoforms, the most expressed in MH1C1 cells, were monitored. After pre-treatment with CAL, STA and H7, the MC-induced CYP1A1 protein and EROD activity were rapidly reduced with temporal profile similar to the profile of the activity of α and β1 PKC isoforms. Moreover, TPA pre-treatment induced a biphasic effect on EROD activity, and a decline of PKC -βI and -α, in first instance, and -δ and -ε activities later on. These findings clearly show that, in MH1C1 cells, PKC is involved in CYP1A1 regulation and that α and βI classic PKC isoforms play an active role in modulating this process

Genetic Classification of Populations using Supervised Learning

There are many instances in genetics in which we wish to determine whether two candidate populations are distinguishable on the basis of their genetic structure. Examples include populations which are geographically separated, case--control studies and quality control (when participants in a study have been genotyped at different laboratories). This latter application is of particular importance in the era of large scale genome wide association studies, when collections of individuals genotyped at different locations are being merged to provide increased power. The traditional method for detecting structure within a population is some form of exploratory technique such as principal components analysis. Such methods, which do not utilise our prior knowledge of the membership of the candidate populations. are termed \emph{unsupervised}. Supervised methods, on the other hand are able to utilise this prior knowledge when it is available. In this paper we demonstrate that in such cases modern supervised approaches are a more appropriate tool for detecting genetic differences between populations. We apply two such methods, (neural networks and support vector machines) to the classification of three populations (two from Scotland and one from Bulgaria). The sensitivity exhibited by both these methods is considerably higher than that attained by principal components analysis and in fact comfortably exceeds a recently conjectured theoretical limit on the sensitivity of unsupervised methods. In particular, our methods can distinguish between the two Scottish populations, where principal components analysis cannot. We suggest, on the basis of our results that a supervised learning approach should be the method of choice when classifying individuals into pre-defined populations, particularly in quality control for large scale genome wide association studies.Comment: Accepted PLOS On

Two-colour generation in a chirped seeded Free-Electron Laser

We present the experimental demonstration of a method for generating two spectrally and temporally separated pulses by an externally seeded, single-pass free-electron laser operating in the extreme-ultraviolet spectral range. Our results, collected on the FERMI@Elettra facility and confirmed by numerical simulations, demonstrate the possibility of controlling both the spectral and temporal features of the generated pulses. A free-electron laser operated in this mode becomes a suitable light source for jitter-free, two-colour pump-probe experiments

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

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

Implementation of Radio-Frequency Deflecting Devices for Comprehensive High-Energy Electron Beam Diagnosis

In next-generation light sources, high-brightness electron beams are used in a free-electron laser configuration to produce light for use by scientists and engineers in numerous fields of research. High-brightness beams are described for such light sources as having low transverse and longitudinal emittances, high peak currents, and low slice emittance and energy spread. The optimal generation and preservation of such high-brightness electron beams during the acceleration process and propagation to and through the photon-producing element is imperative to the quality and performance of the light source. To understand the electron beam's phase space in the accelerating section of a next-generation light source machine, we employed radio-frequency cavities operating in a deflecting mode in conjunction with a magnetic spectrometer and imaging system for both low (250 MeV) and high (1.2 GeV) electron energies. This high-resolution, high-energy system is an essential diagnostic for the optimization and control of the electron beam in the FERMI light source generating fully transversely and longitudinally coherent light in the VUV to soft x-ray wavelength regimes. This device is located at the end of the linear accelerator in order to provide the longitudinal phase space nearest to the entrance of the photon-producing beam-lines. Here, we describe the design, fabrication, characterization, commissioning, and operational implementation of this transverse deflecting cavity structure diagnostic system for the high-energy (1.2 GeV) regime

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

Effective Theory Approach to the Spontaneous Breakdown of Lorentz Invariance

We generalize the coset construction of Callan, Coleman, Wess and Zumino to theories in which the Lorentz group is spontaneously broken down to one of its subgroups. This allows us to write down the most general low-energy effective Lagrangian in which Lorentz invariance is non-linearly realized, and to explore the consequences of broken Lorentz symmetry without having to make any assumptions about the mechanism that triggers the breaking. We carry out the construction both in flat space, in which the Lorentz group is a global spacetime symmetry, and in a generally covariant theory, in which the Lorentz group can be treated as a local internal symmetry. As an illustration of this formalism, we construct the most general effective field theory in which the rotation group remains unbroken, and show that the latter is just the Einstein-aether theory.Comment: 45 pages, no figures