Adaptive Redundancy Management for Durable P2P Backup

We design and analyze the performance of a redundancy management mechanism for Peer-to-Peer backup applications. Armed with the realization that a backup system has peculiar requirements -- namely, data is read over the network only during restore processes caused by data loss -- redundancy management targets data durability rather than attempting to make each piece of information availabile at any time. In our approach each peer determines, in an on-line manner, an amount of redundancy sufficient to counter the effects of peer deaths, while preserving acceptable data restore times. Our experiments, based on trace-driven simulations, indicate that our mechanism can reduce the redundancy by a factor between two and three with respect to redundancy policies aiming for data availability. These results imply an according increase in storage capacity and decrease in time to complete backups, at the expense of longer times required to restore data. We believe this is a very reasonable price to pay, given the nature of the application. We complete our work with a discussion on practical issues, and their solutions, related to which encoding technique is more suitable to support our scheme

Le Elezioni Politiche 2013

Le elezioni politiche del 24 e 25 febbraio 2013 hanno sancito un forte cambiamento della struttura del sistema partitico italiano. In un contesto di altissima volatilità elettorale e di accelerato declino della partecipazione al voto, il sistema è divenuto sostanzialmente tripolare, dopo vent’anni di strutturazione e tenuta del bipolarismo. A questo esito hanno concorso da un lato l’erosione dei principali schieramenti politici che a partire dal novembre 2011 avevano sostenuto l’esperienza del governo Monti (nonché la deludente prova elettorale dello stesso Presidente del Consiglio uscente), e dall’altro lo straordinario successo del Movimento 5 stelle. Quest’ultimo, al primo test elettorale di livello nazionale, ha raccolto un risultato sorprendente, giungendo ad oltre un quarto dei voti validi. Siamo di fronte ad una parentesi momentanea dovuta all’effetto combinato di crisi economica e crisi politica, oppure le contraddizioni interne alla Seconda Repubblica l’hanno condotta effettivamente al suo crepuscolo? Come uscirà il sistema partitico italiano da questa nuova fase di destabilizzazione? Questo quarto Dossier CISE, che raccoglie contributi apparsi sul sito web del Cise prima e dopo le elezioni, fornisce una prima analisi del voto, presentando elaborazioni su dati aggregati, stime dei flussi elettorali, alcune prime analisi su dati di sondaggio, nonché una panoramica dei nuovi eletti e un’appendice ricca di tabelle e mappe riassuntive del risultato elettorale. Come i precedenti Dossier, si tratta di uno strumento prodotto rapidamente all’indomani del voto, con l’intento di suggerire primi spunti di interpretazione da approfondire in seguito, cercando di contribuire alla lettura di un risultato elettorale cruciale, in una delicata fase di cambiamento del sistema partitico italiano

Musculoskeletal Features without Ataxia Associated with a Novel de novo Mutation in KCNA1 Impairing the Voltage Sensitivity of Kv1.1 Channel

The KCNA1 gene encodes the subunit of the voltage-gated Kv1.1 potassium channel that critically regulates neuronal excitability in the central and peripheral nervous systems. Mutations in KCNA1 have been classically associated with episodic ataxia type 1 (EA1), a movement disorder triggered by physical and emotional stress. Additional features variably reported in recent years include epilepsy, myokymia, migraine, paroxysmal dyskinesia, hyperthermia, hypomagnesemia, and cataplexy. Interestingly, a few individuals with neuromyotonia, either isolated or associated with skeletal deformities, have been reported carrying variants in the S2–S3 transmembrane segments of Kv1.1 channels in the absence of any other symptoms. Here, we have identified by whole-exome sequencing a novel de novo variant, T268K, in KCNA1 in a boy displaying recurrent episodes of neuromyotonia, muscle hypertrophy, and skeletal deformities. Through functional analysis in heterologous cells and structural modeling, we show that the mutation, located at the extracellular end of the S3 helix, causes deleterious effects, disrupting Kv1.1 function by altering the voltage dependence of activation and kinetics of deactivation, likely due to abnormal interactions with the voltage sensor in the S4 segment. Our study supports previous evidence suggesting that specific residues within the S2 and S3 segments of Kv1.1 result in a distinctive phenotype with predominant musculoskeletal presentation

The SPTLC1 p.S331 mutation bridges sensory neuropathy and motor neuron disease and has implications for treatment

Aims SPTLC1-related disorder is a late onset sensory-autonomic neuropathy associated with perturbed sphingolipid homeostasis which can be improved by supplementation with the serine palmitoyl-CoA transferase (SPT) substrate, l-serine. Recently, a juvenile form of motor neuron disease has been linked to SPTLC1 variants. Variants affecting the p.S331 residue of SPTLC1 cause a distinct phenotype, whose pathogenic basis has not been established. This study aims to define the neuropathological and biochemical consequences of the SPTLC1 p.S331 variant, and test response to l-serine in this specific genotype. Methods We report clinical and neurophysiological characterisation of two unrelated children carrying distinct p.S331 SPTLC1 variants. The neuropathology was investigated by analysis of sural nerve and skin innervation. To clarify the biochemical consequences of the p.S331 variant, we performed sphingolipidomic profiling of serum and skin fibroblasts. We also tested the effect of l-serine supplementation in skin fibroblasts of patients with p.S331 mutations. Results In both patients, we recognised an early onset phenotype with prevalent progressive motor neuron disease. Neuropathology showed severe damage to the sensory and autonomic systems. Sphingolipidomic analysis showed the coexistence of neurotoxic deoxy-sphingolipids with an excess of canonical products of the SPT enzyme. l-serine supplementation in patient fibroblasts reduced production of toxic 1-deoxysphingolipids but further increased the overproduction of sphingolipids. Conclusions Our findings suggest that p.S331 SPTLC1 variants lead to an overlap phenotype combining features of sensory and motor neuropathies, thus proposing a continuum in the spectrum of SPTLC1-related disorders. l-serine supplementation in these patients may be detrimental