833 research outputs found

    Correlation Analysis of Simultaneously Collected Bistatic and Monostatic Sea Clutter

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    In this work we analyse the correlation properties of simultaneous bistatic and monostatic polarimetric sea clutter data, collected by the NetRAD multistatic radar system. In particular, we study the temporal autocorrelation and cross-correlation functions of the texture and speckle samples, as a function of the system geometry and of the polarization of the transmitter and receiver antennas. These features can vary significantly as a function of bistatic angle and the goal of this paper is to quantify these variations and extract any trends that are observed

    Driving with no brakes: Molecular pathophysiology of Kv7 potassium channels

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    Kv7 potassium channels regulate excitability in neuronal, sensory, and muscular cells. Here, we describe their molecular architecture, physiological roles, and involvement in genetically determined channelopathies highlighting their relevance as targets for pharmacological treatment of several human disorders

    Gating currents from Kv7 channels carrying neuronal hyperexcitability mutations in the voltage-sensing domain

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    Changes in voltage-dependent gating represent a common pathogenetic mechanism for genetically inherited channelopathies, such as benign familial neonatal seizures or peripheral nerve hyperexcitability caused by mutations in neuronal K(v)7.2 channels. Mutation-induced changes in channel voltage dependence are most often inferred from macroscopic current measurements, a technique unable to provide a detailed assessment of the structural rearrangements underlying channel gating behavior; by contrast, gating currents directly measure voltage-sensor displacement during voltage-dependent gating. In this work, we describe macroscopic and gating current measurements, together with molecular modeling and molecular-dynamics simulations, from channels carrying mutations responsible for benign familial neonatal seizures and/or peripheral nerve hyperexcitability; K(v)7.4 channels, highly related to K(v)7.2 channels both functionally and structurally, were used for these experiments. The data obtained showed that mutations affecting charged residues located in the more distal portion of S(4) decrease the stability of the open state and the active voltage-sensing domain configuration but do not directly participate in voltage sensing, whereas mutations affecting a residue (R4) located more proximally in S(4) caused activation of gating-pore currents at depolarized potentials. These results reveal that distinct molecular mechanisms underlie the altered gating behavior of channels carrying disease-causing mutations at different voltage-sensing domain locations, thereby expanding our current view of the pathogenesis of neuronal hyperexcitability diseases

    Studio ab-initio di materiali atti all'immagazzinamento dell'idrogeno

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    Nell'ambito di attuali ricerche di materiali atti all'immagazzinamento dell'idrogeno, il composto intermetallico Litio-Alluminio rappresenta uno dei più promettenti candidati. Inoltre, le sue interessanti proprietà elettroniche e la sua caratteristica struttura, B32, lo rendono un materiale molto attraente dal punto di vista teorico. Il lavoro di tesi, svolto presso il politecnico di Zurigo (ETHZ) all'interno del gruppo di ricerca in Scienze Computazionali guidato dal Prof. Michele Parrinello con sede a Lugano, ha riguardato una caratterizzazione elettronica e strutturale del composto binario LiAl. L'approccio per la risoluzione del problema many-electron è stato completamente ab-initio. Nello schema della Teoria del Funzionale della Densità (DFT), sono stati usati codici basati su un utilizzo di onde piane per la rappresentazione degli stati di Kohn e Sham assieme all'impiego di pseudopotenziali per la descrizione degli atomi costituenti Li e Al. Un aspetto molto interessante del lavoro è stato lo studio del più realistico sistema in presenza di vacanze di Li. Anche in questo caso l'implementazione dei calcoli, per la risoluzione del problema, è stata eseguita da principi primi

    REVERSE MODELLING PROCESS TO SUPPORT OF A FLEMISH WOODEN ALTARPIECE PHYSICAL RESTORATION

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    This study focuses on digital Computer Aided Restoration procedures to guide the complex physical restoration of an artwork, innovating and implementing traditional survey methods. As a case study some results are presented of a complex and articulated conservative restoration project on a sculpted and painted wing altar, preserved in the Regional Gallery of Sicily in Palazzo Abatellis, Palermo. The application of non-invasive and high information density 3D survey methodologies allowed to record and integrate into a unique digital platform (designed within the UnReal Engine) a wide quantity of heterogeneous data which document the work's state (diagnostic analyses, graphical annotation, historical information). The multidisciplinary investigation process is aimed to guide the disassembly of the various components, to tell the long process of activity in the laboratory and to experiment the realization and integration of missing parts. The innovative application of 3D digital technologies shows how the integrated use of the new technology can be a useful tool for improving the conservation of a work of art. The data processed have permitted a better interpretative reading, implementing the knowledge of the scholars, and a more effective communication and fruition to the audience

    Specification of skeletal muscle differentiation by repressor element-1 silencing transcription factor (REST)-regulated Kv7.4 potassium channels

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    Changes in the expression of potassium (K(+)) channels is a pivotal event during skeletal muscle differentiation. In mouse C(2)C(12) cells, similarly to human skeletal muscle cells, myotube formation increased the expression of K(v)7.1, K(v)7.3, and K(v)7.4, the last showing the highest degree of regulation. In C(2)C(12) cells, K(v)7.4 silencing by RNA interference reduced the expression levels of differentiation markers (myogenin, myosin heavy chain, troponinT-1, and Pax3) and impaired myotube formation and multinucleation. In K(v)7.4-silenced cells, the differentiation-promoting effect of the K(v)7 activator N-(2-amino-4-(4-fluorobenzylamino)-phenyl)-carbamic acid ethyl ester (retigabine) was abrogated. Expression levels for the repressor element-1 silencing transcription factor (REST) declined during myotube formation. Transcript levels for K(v)7.4, as well as for myogenin, troponinT-1, and Pax3, were reduced by REST overexpression and enhanced upon REST suppression by RNA interference. Four regions containing potential REST-binding sites in the 5′ untranslated region and in the first intron of the K(v)7.4 gene were identified by bioinformatic analysis. Chromatin immunoprecipitation assays showed that REST binds to these regions, exhibiting a higher efficiency in myoblasts than in myotubes. These data suggest that K(v)7.4 plays a permissive role in skeletal muscle differentiation and highlight REST as a crucial transcriptional regulator for this K(+) channel subunit

    Correlating the Clinical and Genetic Features of Benign Familial Neonatal Seizures (BFNS) with the Functional Consequences of Underlying Mutations

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    Almost ten years have passed since the identification of Kv7.2 and Kv7.3, the genes altered in benign familial neonatal seizures (BFNS), a familial autosomal dominant focal epilepsy of the newborn. Despite the rarity of the disease, clinical and genetic data have been gathered from more than 50 BFNS-affected families; these studies reveal that each family harbours a specific disease-causing mutation, and that the mutation-induced functional changes range from a subtle alteration in channel behaviour to a complete ablation of channel function. Prompted by the recent identification of peculiar gating changes in Kv7.2 subunits caused by novel mutations responsible for BFNS, in the present work we attempt to link, whenever possible, the specific genetic defect with the clinical evolution of the disease in the affected families on one side, and, on the other, with the functional defects revealed by expression studies. Such genotype-phenotype correlations may provide clues on the pathogenesis of the wide variety of neuropsychiatric manifestations often associated to BFNS, and should foster our attempts to gain more detailed functional information which might help to elucidate the pathogenetic mechanisms of the disease

    Occult renal dysfunction:a mortality and morbidity risk factor in coronary artery bypass grafting surgery

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    ObjectiveElevated preoperative serum creatinine is considered an independent risk factor for postoperative mortality and morbidity in patients undergoing coronary artery bypass grafting. However, the impact of occult renal dysfunction, defined as an impairment of glomerular filtration rate with normal serum creatinine, is still unknown. The aim of this study was to analyze the effects of occult renal dysfunction on early outcomes after coronary artery bypass grafting.MethodsThis was a retrospective, observational, cohort study of prospectively collected data on 9159 consecutive patients with normal serum creatinine levels undergoing coronary artery bypass grafting between April 1996 and February 2009. Patients were divided into two groups based on preoperative creatinine clearance estimated with the Cockcroft-Gault equation: 5484 patients with a creatinine clearance ≥ 60 mL/min and 3675 patients with a creatinine clearance < 60 mL/min (occult renal dysfunction group).ResultsOverall in-hospital mortality was 1%. Occult renal dysfunction was associated with a doubling in the risk of operative mortality (1.4% vs 0.7%; P = .001), postoperative renal dysfunction (5.1% vs 2.5%; P < .0001), and need for dialysis (0.8% vs 0.4%; P = .014). Moreover, occult renal dysfunction increased the risk of stroke (1% vs 0.3%; P < .0001), arrhythmia (28.5% vs 21.2%; P < .0001), and hospital stay > 7 days (36.45 vs 24.5%; P < .0001). In a multivariable analysis adjusting for preoperative risk factors, occult renal dysfunction was confirmed to be an independent predictor of mortality (odds ratio, 1.72), postoperative renal dysfunction (odds ratio, 1.9), dialysis (odds ratio, 1.82), stroke (odds ratio, 2.6) arrhythmia (odds ratio, 1.42), and hospital stay > 7 days (odds ratio, 1.65).ConclusionsOccult renal dysfunction is an independent risk factor for early mortality and morbidity in patients undergoing coronary artery bypass grafting
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