Inner Ear Organoids: Strengths and Limitations

Inner ear organoids derived from differentiation of human pluripotent stem cells have recently gained momentum as tools to study inner ear development and developmental defects. An additional exciting aspect about this technology is represented by its translational potential, specifically, the use of organoids to validate therapeutics for hearing and balance restoration on human/patient-specific cells. This latter aspect will be briefly discussed here including opportunities and current limitations

Towards the assessment of the flood attenuation potential of italian dams: first steps and sensitivity to basic model features

The effect of reservoirs on downstream flood regime has been largely investigated in the literature worldwide, but there is, to date, still an insufficient elaboration on the “natural” flood peak mitigation exerted by dams. In this work, the attenuation potential of flood peaks by the main Italian reservoirs is devised, based on a small number of objective factors that concur to the implementation of a ranking method. This can be used to select priorities in the implementation of Dam Emergency Plans in Italy, according to a legislation act of 2004. The attenuation potential is estimated here by means of a very simple procedure, that does not require the definition a priori of a hydrograph shape and the mitigation effect is computed assuming that the dam operates as a linear reservoir, meaning that the stored volume and the outflow are linked by a linear relationship. A realistic average annual design flood peak has been estimated for each basin upstream the dams through the rational method, using for the first time the results of a countrywide analysis of rainfall extremes. The study has been carried out using 265 dams and related watersheds throughout Italy. Results were examined in terms of both magnitude and order position of the attenuation coefficient: a strong sensitivity to the time of concentration is apparent

Gor'kij: il mito, l'oblio, la voglia di riscoperta

Lo scopo del lavoro è presentare la traduzione del primo capitolo della biografia di Maksim Gor’kij scritta da Dmitrij Bykov. Si tratta di una scelta influenzata dall’obiettivo che questa biografia mira a raggiungere: far uscire Gor’kij dall’oblio in cui è caduto. L’autore, con questo testo, vuol infatti riportare alla luce una figura intellettuale fondamentale della cultura russa. Se per Bykov lo scopo del suo lavoro è la “riscoperta” di Gor’kij, per il lettore italiano, invece, la traduzione potrebbe essere un modo per conoscere una figura importante del panorama culturale russo, un intellettuale che ha vissuto uno dei capitoli chiave della sua vita proprio in Italia, a Capri. Purtroppo data la lunghezza dell’opera non mi è sembrato opportuno riportare una traduzione integrale in questa sede, pertanto ho scelto di presentare solo il primo capitolo dell’opera. Ho deciso di non operare una selezione all’interno del testo, in quanto non sembrava una soluzione valida: trattandosi di una biografia non si presentano infatti problemi relativi alla trama dell’opera. Ho scelto di tradurre il primo capitolo perché lo ritengo la chiave di lettura della biografia. Nelle prime pagine, infatti, Bykov rende noto il senso del titolo svelandone il collegamento con il testo dello stesso Gork’ij La vita di Klim Samgin e, sempre nel primo capitolo, l’autore delinea la parabola della vita letteraria di Gor’kij: da essere mitizzato a essere del tutto “dimenticato”. L’importanza della parte iniziale del libro è da ricercarsi anche in un altro motivo. I primi anni di vita del giovane Peškov, dei quali Bykov non ci risparmia gli episodi più violenti, influenzano il comportamento e il pensiero del Gor’kij maturo, inoltre, qui l’autore ci fa assistere al passaggio da Aleksej Peškov a Maksim Gor’kij: «Come se volesse ricominciare tutto da zero, affinché la vita letteraria non avesse niente a che vedere con quella reale. Il nome non era solo un ricordo legato al padre ma anche una indicazione del massimalismo verso tutto; mentre Gor’kij era un tributo al pessimo romanticismo, che ci vuoi fare, di amarezza ne aveva vista abbastanza.» Questo elaborato si compone di due capitoli, più le conclusioni e la bibliografia, seguiti dalla mia proposta di traduzione. Nel primo capitolo ho presentato “la costruzione di Dio”, il movimento che faceva capo a Gor’kij e Lunačarskij nel quale si ipotizzava una divinizzazione laica del popolo. Questo mi ha permesso di mettere in risalto l’importanza che aveva raggiunto Gor’kij, e quanto il suo pensiero influenzasse il panorama culturale e politico russo dell’epoca. Definire Gor’kij uno “scrittore” diventa, quindi, altamente riduttivo. Il secondo capitolo si articola in due paragrafi. Nel primo ho fatto un excursus all’interno della teoria della traduzione. Ho ritenuto importante fare questo passaggio prima di passare ad analizzare le scelte traduttive per inserire nel migliore dei modi il lettore nel mondo della traduzione. Ho cercato di presentare i diversi punti di vista su tale disciplina per sottolineare che l’attività vera e propria del tradurre non segue dei parametri prefissati e non ha una soluzione univoca. Ѐ proprio questo ciò che rende viva e interessante questa disciplina. Dall’excursus emerge quanto il dibattito sulla teoria e sulle strategie traduttive mi abbia coinvolto. Nel secondo paragrafo, invece, attraverso l’analisi del testo di partenza, vengono presentate e giustificate le scelte traduttive da me adottate, riportando citazioni ed esempi

Flood Attenuation Potential of Italian Dams: Sensitivity on Geomorphic and Climatological Factors

In this work the attenuation potential of flood peaks of 265 large reservoirs all over Italy is analysed, considering a flood management that excludes gates opening and then configures strictly unsupervised attenuation effects. Key factors of dams and related basins are considered to develop a ranking method that can emphasize the interplay between dam geometry and the hydrological processes acting in the upstream watershed. To maintain a homogeneous approach in such a wide geographic area, the attenuation index is computed applying the numerical solution of the differential equation of lakes and only two different standardized hydrograph shapes have been used. An index design flood from the rational method is used as the incoming peak value for each dam, enhancing the use of the results of a recent analysis of all Italian rainfall extremes. Even with a very simple approach, twentyfour different design incoming floods are derived, by varying the shape of the incoming hydrograph and the parameters of the rational method. Exploring the ranking results in all the alternatives, the attenuation potential obtained for all dams demonstrates to be strongly sensitive to the assumptions on the time of concentration and to some rainfall features. On the other hand, the hydrograph shape seems to exert much less influence on the ranking outcome. Results obtained can be useful to studies of wide-area flood frequency analyses, as we highlighted the sensitivity of the rank of attenuation efficiency to hydrologic parameters widely used in the assessment of the design flood peaks in ungauged basins

Sensitivity of Italian dams' flood mitigation capacity to the combined effect of morphological and climatological factors

The management of reservoirs during flood events has been widely investigated to support real-time gates operation. However, there is still an insufficient elaboration of the assessment of average peak flow mitigation of dams to be used, for instance, in flood frequency analyses. Here the “natural” flood attenuation potential of 265 large reservoirs all over Italy is devised, in terms of the development of a Mitigation Efficiency Ranking (MER) based on just a few basin and dam essential factors. Simplified, yet rigorous and homogeneous assessment of MER can be used to prioritise the implementation of Dam Emergency Plans in Italy and to support similar initiatives worldwide. To maintain homogeneity in such a wide area, standardized hydrograph shapes are used and index-flood from the rational method is adopted as the incoming peak value, enhancing the results of a recent analysis of all Italian rainfall extremes. The attenuation index is computed by solving the differential equation of lakes. Twenty-four different design floods were derived adopting only two hydrograph shapes and minimal parameter options, i.e., the basin runoff coefficient, the time of concentration and the parameters of the Intensity-Duration-Frequency (IDF) curve. The MER results for the 265 dammed watersheds in all the tested configurations demonstrate to be strongly sensitive to the assumptions on the time of concentration and to some rainfall features, while, for instance, the hydrograph shape seems to exert much less influence on the ranking outcome. This analysis will be part of the research framework of the RETURN Extended Partnership Project

Rescue of spinal muscular atrophy mouse models with AAV9-Exon-specific U1 snRNA

Spinal Muscular Atrophy results from loss-of-function mutations in SMN1 but correcting aberrant splicing of SMN2 offers hope of a cure. However, current splice therapy requires repeated infusions and is expensive. We previously rescued SMA mice by promoting the inclusion of a defective exon in SMN2 with germline expression of Exon-Specific U1 snRNAs (ExspeU1). Here we tested viral delivery of SMN2 ExspeU1s encoded by adeno-associated virus AAV9. Strikingly the virus increased SMN2 exon 7 inclusion and SMN protein levels and rescued the phenotype of mild and severe SMA mice. In the severe mouse, the treatment improved the neuromuscular function and increased the life span from 10 to 219 days. ExspeU1 expression persisted for 1 month and was effective at around one five-hundredth of the concentration of the endogenous U1snRNA. RNA-seq analysis revealed our potential drug rescues aberrant SMA expression and splicing profiles, which are mostly related to DNA damage, cell-cycle control and acute phase response. Vastly overexpressing ExspeU1 more than 100-fold above the therapeutic level in human cells did not significantly alter global gene expression or splicing. These results indicate that AAV-mediated delivery of a modified U1snRNP particle may be a novel therapeutic option against SMA

Trial and error mathematics I: dialectical and quasi-dialectical systems

We define and study quasi-dialectical systems, which are an extension of Magari’s dialectical systems, designed to make Magari’s formalization of trial and error mathematics more adherent to the real mathematical practice of revision: our proposed extension follows, and in several regards makes more precise, varieties of empiricist positions a` la Lakatos. We prove severalproperties of quasi-dialectical systems and of the sets that they represent, called quasi-dialecticalsets. In particular, we prove that the quasi-dialectical sets are Delta-0-2 sets in the arithmetical hierarchy. We distinguish between “loopless” quasi-dialectal systems, and quasi-dialectical systems “with loops”. The latter ones represent exactly those coinfinite c.e. sets, that are not simple. In a subsequent paper we will show that whereas the dialectical sets are \omega-c.e., the quasi-dialectical sets spread out throughout all classes of the Ershov hierarchy of the Delta-0-2 sets