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Despite the recent increase in Virtual Reality (VR) technologies employed for training manufacturing operators on industrial robotic tasks, the impact of VR methods compared to traditional ones is still unclear. This paper presents an experimental comparison of the two training approaches, with novice operators performing the same manufacturing tasks with a VR robot and with a real robot. The hardware selected is an ABB IRB 120 industrial robot, a HTC Vive head mounted display to operate it, besides a corresponding VR model developed in Unity. Twenty-four students performed two actions — drawing and “pick and place” -– in tasks with increasing difficulty, with both the VR model and the real robot. Completion time and task pass rate are adopted to estimate the learning efficiency, while a questionnaire evaluates the users’ satisfaction. The results show that students using VR overall need less elapsed time to complete all tasks, and they record a higher pass rate. The questionnaire answers show that 83% of participants find the VR model helpful in familiarizing with the real robot, and 75% are in favor of using the virtual tool for training novice operators. Users also report that moving the real robot is more complex than the virtual one; adjusting the speed is harder and the possibility of causing damage is worrisome, whereas the VR robot feels safer to operate and easier to drive. The majority of students are satisfied with the design of the tasks, and feel content with the experience. The main finding is that learning from a VR model allows to master driving a real robot quickly and easily. VR training is more useful than conventional methods because it reduces the learning time, allows for training without hindering production, lowers the risk perception, and improves safety for operators and industrial equipment. QC 20221116

The last Intergovernmental Panel on Climate Change (IPPC) assessment report highlighted how actions to reduce CO2 emissions have not been effective so far to achieve the 1.5 C limit and that radical measures are required. Solutions such as the upgrading of waste biomass, the power-to-X paradigm, and an innovative energy carrier such as hydrogen can make an effective contribution to the transition toward a low-carbon energy system. In this context, the aim of this study is to improve the hydrogen production process from wet residual biomass by examining the advantages of an innovative integration of anaerobic digestion with thermochemical transformation processes. Furthermore, this solution is integrated into a hybrid power supply composed of an electric grid and a photovoltaic plant (PV), supported by a thermal energy storage (TES) system. Both the performance of the plant and its input energy demand—splitting the power request between the photovoltaic system and the national grid—are carefully assessed by a Simulink/Simscape model. The preliminary evaluation shows that the plant has good performance in terms of hydrogen yields, reaching 5.37% kgH2/kgbiomass, which is significantly higher than the typical value of a single process (approximately 3%). This finding demonstrates a good synergy between the biological and thermochemical biomass valorization routes. Moreover, thermal energy storage significantly improves the conversion plant’s independence, almost halving the energy demand from the grid.

On August 21, 2017, the volcanic island of Ischia was struck by a Mw 3.9 (http://cnt.rm.ingv.it/event/16796811) earthquake which caused two victims and heavy damages on wide portions of the Casamicciola Terme, Lacco Ameno and Forio municipalities. Following the Decree 1/2018 of the Government Commission for the reconstruction of damaged areas of Ischia Island, a Grade 3 Seismic Microzonation study was committed by each municipality to private consultants, who were scientifically supported by a multidisciplinary team of geologists, geophysicists and geotechnical engineers from CNR, INGV and University of Naples "Federico II". The existing data from previous geological and geotechnical investigations were integrated with the results of new geo-lithological surveys and geophysical measurements (HVSR, MASW, Down hole tests) carried out by the consultants. The whole amount of data was quality checked, homogenized and collected in a SQLite/SpatiaLite geodatabase using a QGIS open source software by the support team. A geo-lithological map of northern and western sides of the island was then produced, and the results of routine geophysical tests were coupled with those of seismic 2D ambient vibration arrays, to obtain shear wave velocity profiles (several hundreds of meters deep) down to the seismic bedrock, made of lithic tuffs and lavas, and to define its buried morphology. This in turn enabled to draw a map of seismically homogeneous microzones of the entire study area. Cyclic torsional shear tests were carried out on 10 undisturbed soil samples, mainly taken from epiclastic cover deposits, to characterize their non-linear behavior to be adopted for seismic response analyses. These latter were carried out along 1D profiles characterizing each microzone and along selected 2D cross sections running from the Mount Epomeo to the coast. The dynamic analyses allowed to detect and map areas characterized by variable amplification factors, of spectral accelerations throughout different ranges of periods (0.1-0.5s, 04.-0.8s, 0.7-1.1 s). The zones most prone to site amplification are those corresponding to localized graben-like depressions at the toe of Mount Epomeo, such as Maio neighborhood of Casamicciola, where thickened epiclastic covers are entrenched into blocks of uplifted bedrock and where a combination of 1D stratigraphic amplification and 2D reflection and diffraction effects is expected.

BackgroundEven though breast cancer is the most frequent extra-abdominal tumor causing peritoneal metastases, clear clinical guidelines are lacking. Our aim is to establish whether cytoreductive surgery (CRS) could be considered in selected patients with peritoneal metastases from breast cancer (PMBC) to manage abdominal spread and allow patients to resume or complete other medical treatments.MethodsWe considered patients with PMBC treated in 10 referral centers from January 2002 to May 2019. Clinical data included primary cancer characteristics (age, histology, and TNM) and data on metastatic disease (interval between primary BC and PM, molecular subtype, other metastases, and peritoneal spread). Overall survival (OS) was estimated using the Kaplan–Meier method. Univariate and multivariable data for OS were analyzed using the Cox proportional hazards model.ResultsOf the 49 women with PMBC, 20 were treated with curative aim (CRS with or without HIPEC) and 29 were treated with non-curative procedures. The 10-year OS rate was 27%. Patients treated with curative intent had a better OS than patients treated with non-curative procedures (89.2% vs. 6% at 36 months, p < 0.001). Risk factors significantly influencing survival were age at primary BC, interval between BC and PM diagnosis, extra-peritoneal metastases, and molecular subtype.ConclusionsThe improved outcome in selected cases after a multidisciplinary approach including surgery should lead researchers to regard PMBC patients with greater attention despite their scarce epidemiological impact. Our collective efforts give new information, suggest room for improvement, and point to further research for a hitherto poorly studied aspect of metastatic BC.

The dentate gyrus of the hippocampus is one of two brain areas generating throughout life new neurons, which contribute to the formation of episodic/associative memories. During aging, the production of new neurons decreases and a cognitive decline occurs. Dietary factors influence neuronal function and synaptic plasticity; among them the phenolic compound hydroxytyrosol (HTyr), present in olive oil, displays neuroprotective effects. As age impacts primarily on the hippocampus-dependent cognitive processes, we wondered whether HTyr could stimulate hippocampal neurogenesis in vivo in adult and aged wild-type mice as well as in the B-cell translocation 1 gene (Btg1) knockout mouse model of accelerated neural aging. We found that treatment with HTyr activates neurogenesis in the dentate gyrus of adult, aged, and Btg1-null mice, by increasing survival of new neurons and decreasing apoptosis. Notably, however, in the aged and Btg1-null dentate gyrus, HTyr treatment also stimulates the proliferation of stem and progenitor cells, whereas in the adult dentate gyrus HTyr lacks any proliferative effect. Moreover, the new neurons generated in aged mice after HTyr treatment are recruited to existing circuits, as shown by the increase of BrdU(+)/c-fos(+) neurons. Finally, HTyr treatment also reduces the markers of aging lipofuscin and Iba1. Overall, our findings indicate that HTyr treatment counteracts neurogenesis decline during aging.

The investigation of soil response to dynamic loads is necessary to predict site-specific seismic hazard. This paper presents the results of cyclic and dynamic laboratory tests carried out after the 2016–2017 Central Italy Earthquake sequence, within the framework of the seismic microzonation studies of the most damaged municipalities in the area. The database consists of 79 samples investigated by means of dynamic resonant column tests, cyclic torsional shear tests or cyclic direct simple shear tests. Results are firstly analysed in terms of field and laboratory values of small-strain shear wave velocity, highlighting the influence of the sample disturbance and of the mean effective consolidation pressure. The cyclic threshold shear strains as a function of plasticity index are then compared with findings from the published literature and the outliers are analysed. Subsequently, the dynamic soil behaviour is investigated with reference to the small-strain damping ratio. Differences between results from different tests are analysed in the light of the loading frequencies. Finally, the database is used to develop a predictive model for soil nonlinear curves according to plasticity index, mean effective confining stress, and loading frequency. The model represents a useful tool to predict the nonlinear stress–strain behaviour of Central Italy soils, necessary to perform site-specific ground response analyses.

The dentate gyrus of the hippocampus and the subventricular zone are neurogenic niches where neural stem and progenitor cells replicate throughout life to generate new neurons. The Btg1 gene maintains the stem cells of the neurogenic niches in quiescence. The deletion of Btg1 leads to an early transient increase of stem/progenitor cells division, followed, however, by a decrease during adulthood of their proliferative capability, accompanied by apoptosis. Since a physiological decrease of neurogenesis occurs during aging, the Btg1 knockout mouse may represent a model of neural aging. We have previously observed that the defective neurogenesis of the Btg1 knockout model is rescued by the powerful neurogenic stimulus of physical exercise (running). To identify genes responsible for stem and progenitor cells maintenance, we sought here to find genes underlying this premature neural aging, and whose deregulated expression could be rescued by running. Through RNA sequencing we analyzed the transcriptomic profiles of the dentate gyrus isolated from Btg1 wild-type or Btg1 knockout adult (2-month-old) mice submitted to physical exercise or sedentary. In Btg1 knockout mice, 545 genes were deregulated, relative to wild-type, while 2081 genes were deregulated by running. We identified 42 genes whose expression was not only down-regulated in the dentate gyrus of Btg1 knockout, but was also counter-regulated to control levels by running in Btg1 knockout mice, vs. sedentary. Among these 42 counter-regulated genes, alpha-synuclein (Snca), Fos, Arc and Npas4 showed significantly greater differential regulation. These genes control neural proliferation, apoptosis, plasticity and memory and are involved in aging. In particular, Snca expression decreases during aging. We tested, therefore, whether an Snca-expressing lentivirus, by rescuing the defective Snca levels in the dentate gyrus of Btg1 knockout mice, could also reverse the aging phenotype, in particular the defective neurogenesis. We found that the exogenous expression of Snca reversed the Btg1 knockout-dependent decrease of stem cell proliferation as well as the increase of progenitor cell apoptosis. This indicates that Snca has a functional role in the process of neural aging observed in this model, and also suggests that Snca acts as a positive regulator of stem cell maintenance.

We have previously generated a mouse model (Ptch1+/−/Tis21KO), which displays high frequency spontaneous medulloblastoma, a pediatric tumor of the cerebellum. Early postnatal cerebellar granule cell precursors (GCPs) of this model show, in consequence of the deletion of Tis21, a defect of the Cxcl3-dependent migration. We asked whether this migration defect, which forces GCPs to remain in the proliferative area at the cerebellar surface, would be the only inducer of their high frequency transformation. In this report we show, by further bioinformatic analysis of our microarray data of Ptch1+/−/Tis21KO GCPs, that, in addition to the migration defect, they show activation of the PI3K/AKT/mTOR pathway, as the mRNA levels of several activators of this pathway (e.g., Lars, Rraga, Dgkq, Pdgfd) are up-regulated, while some inhibitors (e.g. Smg1) are down-regulated. No such change is observed in the Ptch1+/− or Tis21KO background alone, indicating a peculiar synergy between these two genotypes. Thus we investigated, by mRNA and protein analysis, the role of PI3K/AKT/mTOR signaling in MBs and in nodules from primary Ptch1+/−/Tis21KO MB allografted in the flanks of immunosuppressed mice. Activation of the PI3K/AKT/mTOR pathway is seen in full-blown Ptch1+/−/Tis21KO MBs, relative to Ptch1+/−/Tis21WT MBs. In Ptch1+/−/Tis21KO MBs we observe that the proliferation of neoplastic GCPs increases while apoptosis decreases, in parallel with hyper-phosphorylation of the mTOR target S6, and, to a lower extent, of AKT. In nodules derived from primary Ptch1+/−/Tis21KO MBs, treatment with MEN1611, a novel PI3K inhibitor, causes a dramatic reduction of tumor growth, inhibiting proliferation and, conversely, increasing apoptosis, also of tumor CD15+ stem cells, responsible for long-term relapses. Additionally, the phosphorylation of AKT, S6 and 4EBP1 was significantly inhibited, indicating inactivation of the PI3K/AKT/mTOR pathway. Thus, PI3K/AKT/mTOR pathway activation contributes to Ptch1+/−/Tis21KO MB development and to high frequency tumorigenesis, observed when the Tis21 gene is down-regulated. MEN1611 could provide a promising therapy for MB, especially for patient with down-regulation of Btg2 (human ortholog of the murine Tis21 gene), which is frequently deregulated in Shh-type MBs.

We have previously generated a mouse model (Ptch1+/−/Tis21KO), which displays high frequency spontaneous medulloblastoma, a pediatric tumor of the cerebellum. Early postnatal cerebellar granule cell precursors (GCPs) of this model show, in consequence of the deletion of Tis21, a defect of the Cxcl3-dependent migration. We asked whether this migration defect, which forces GCPs to remain in the proliferative area at the cerebellar surface, would be the only inducer of their high frequency transformation. In this report we show, by further bioinformatic analysis of our microarray data of Ptch1+/−/Tis21KO GCPs, that, in addition to the migration defect, they show activation of the PI3K/AKT/mTOR pathway, as the mRNA levels of several activators of this pathway (e.g., Lars, Rraga, Dgkq, Pdgfd) are up-regulated, while some inhibitors (e.g. Smg1) are down-regulated. No such change is observed in the Ptch1+/− or Tis21KO background alone, indicating a peculiar synergy between these two genotypes. Thus we investigated, by mRNA and protein analysis, the role of PI3K/AKT/mTOR signaling in MBs and in nodules from primary Ptch1+/−/Tis21KO MB allografted in the flanks of immunosuppressed mice. Activation of the PI3K/AKT/mTOR pathway is seen in full-blown Ptch1+/−/Tis21KO MBs, relative to Ptch1+/−/Tis21WT MBs. In Ptch1+/−/Tis21KO MBs we observe that the proliferation of neoplastic GCPs increases while apoptosis decreases, in parallel with hyper-phosphorylation of the mTOR target S6, and, to a lower extent, of AKT. In nodules derived from primary Ptch1+/−/Tis21KO MBs, treatment with MEN1611, a novel PI3K inhibitor, causes a dramatic reduction of tumor growth, inhibiting proliferation and, conversely, increasing apoptosis, also of tumor CD15+ stem cells, responsible for long-term relapses. Additionally, the phosphorylation of AKT, S6 and 4EBP1 was significantly inhibited, indicating inactivation of the PI3K/AKT/mTOR pathway. Thus, PI3K/AKT/mTOR pathway activation contributes to Ptch1+/−/Tis21KO MB development and to high frequency tumorigenesis, observed when the Tis21 gene is down-regulated. MEN1611 could provide a promising therapy for MB, especially for patient with down-regulation of Btg2 (human ortholog of the murine Tis21 gene), which is frequently deregulated in Shh-type MBs.

Industrial processes are mainly based on procedural knowledge that must be continually elicited from experienced operators and learned by novice operators. In the context of Industry 4.0, machines already play a key role in knowledge transfer; however, new models and methods based on the artificial intelligence advances of the past few years need to be developed and applied. The future of human-machine collaboration is not limited to physical applications, but it has the potential to harness both the strength of human skills, experience and the computational power provided by the surrounding machines for truly adaptive industrial processes. The winning recipe is a balance between letting humans exploit their inherent experience and letting machines integrate the missing skills to preserve production standards. This work introduces a procedural knowledge model to be used for the design of industrial and scientific adaptive processes and it paves the way to transforming human-machine collaboration into an efficient solution to make industrial and scientific processes resilient to a constantly changing world. Industriella processer baseras huvudsakligen på den procedurella kunskapen som fortlöpande måste tas fram och anpassas av erfarna operatörer och läras in av nybörjare. Inom ramen för Industri 4.0 spelar maskiner redan en nyckelroll i kunskapsöverföring; dock behöver nya modeller och metoder utvecklas och användas, som baseras på de senaste årens framsteg inom artificiell intelligens. Framtiden för samarbete mellan människa och maskin är inte begränsad till fysiska applikationer, utan den har potential att utnyttja såväl styrkan i mänsklig kompetens och erfarenhet som den beräkningskraft som de omgivande maskinerna tillhandahåller, för att åstadkomma verkligt anpassningsbara industriella processer. Det vinnande receptet är att hitta en balans mellan att låta människor utnyttja sina egna erfarenheter och att låta maskiner tillhandahålla de saknade färdigheterna för att kunna följa produktionsstandarder. I detta arbete introduceras en procedurell kunskapsmodell som kan användas för utformning av industriella och vetenskapliga, anpassningsbara processer och banar väg för att omvandla samarbete mellan människor och maskiner till effektiva lösningar för att göra industriella och vetenskapliga processer följsamma i en ständigt föränderlig värld.

Questo articolo scientifico sostiene la tesi che un algoritmo di controllo, facente uso di intelligenza artificiale, per poter essere efficiente necessiti di sfruttare le simmetrie integrate in ogni manipolatore robotico industrale così che quest’ultimo possa essere ulteriormente caratterizzato ed utilizzato. Il prodotto di questo miglioramento è uno spazio discreto a griglia cilindrica quadridimensionale (4D) che può direttamente sostituire complessi modelli robotici. A* è scelto per il suo ampio utilizzo tra simili algoritmi di ricerca, in modo da studiare i vantaggi e gli svantaggi del controllo di robot industriali tramite la griglia discreta cilindrica 4D. Lo studio mostra che questo approccio consente di controllare un robot senza alcuna conoscenza specifica dei modelli cinematici e dinamici del robot al momento della pianificazione e dell’esecuzione. In effetti, le posizioni dei giunti del robot per ciascuna cella della griglia vengono precalcolate e memorizzate come conoscenza, quindi recuperate rapidamente dall’algoritmo di ricerca di percorso quando necessario. Lo spazio discreto cilindrico 4D presenta sia i vantaggi dello spazio di configurazione che dello spazio di lavoro cartesiano tridimensionale del robot. Poiché l’ottimizzazione del percorso è il nucleo di qualsiasi algortimo di ricerca, incluso A*, la griglia cilindrica 4D fornisce uno spazio di ricerca che può incorporare ulteriori conoscenze sotto forma di proprietà delle celle, inclusa la presenza di ostacoli e l’occupazione volumetrica dell’intero corpo del robot industriale, da usare in applicazioni per l’evitamento degli ostacoli. Il compromesso principale è tra una capacità limitata della conosenza precalcolata nella griglia e la velocità di ricerca del percorso migliore. Questo approccio innovativo incoraggia l’uso di algoritmi di ricerca per applicazioni robotiche industriali, apre la via allo studio di altre simmetrie fisiche presenti in altri modelli di robot e pone le basi per l’applicazione di algoritmi dinamici per l’evitamento degli ostacoli.

In the adult mammalian brain new neurons are continuously generated throughout life in two niches, the dentate gyrus of the hippocampus and the subventricular zone. This process, called adult neurogenesis, starts from stem cells, which are activated and enter the cell cycle. The proliferative capability of stem cells progressively decreases during aging. The population of stem cells is generally quiescent, and it is not clear whether the potential for stem cells to expand is limited, or whether they can expand and then return to quiescence, remaining available for further activation. Certain conditions may deregulate stem cells quiescence and self-renewal. In fact we discuss the possibility of activation of stem cells by neurogenic stimuli as a function of the intensity of the stimulus (i.e., whether this is physiological or pathological), and of the deregulation of the system (i.e., whether the model is aged or carrying genetic mutations in the gene network controlling quiescence). It appears that when the system is aged and/or carrying mutations of quiescence-maintaining genes, preservation of the quiescent state of stem cells is more critical and stem cells can be activated by a neurogenic stimulus which is ineffective in normal conditions. Moreover, when a neurogenic stimulus is in itself a cause of brain damage (e.g., kainic acid treatment) the activation of stem cells occurs bypassing any inhibitory control. Plausibly, with strong neurogenic stimuli, such as kainic acid injected into the dentate gyrus, the self-renewal capacity of stem cells may undergo rapid exhaustion. However, the self-renewal capability of stem cells persists when normal stimuli are elicited in the presence of a mutation of one of the quiescence-maintaining genes, such as p16Ink4a, p21Cip1 or Btg1. In this case, stem cells become promptly activated by a neurogenic stimulus even during aging. This indicates that stem cells retain a high proliferative capability and plasticity, and suggests that stem cells are protected against the response to stimulus and are resilient to exhaustion. It will be interesting to assess at which functional degree of deregulation of the quiescence-maintaining system, stem cells will remain responsive to repeated neurogenic stimuli without undergoing exhaustion of their pool.

Of wide interest for health is the relation existing between depression, a very common psychological illness, accompanied by anxiety and reduced ability to concentrate, and adult neurogenesis. We will focus on two neurogenic stimuli, fluoxetine and physical exercise, both endowed with the ability to activate adult neurogenesis in the dentate gyrus of the hippocampus, known to be required for learning and memory, and both able to counteract depression. Fluoxetine belongs to the class of selective serotonin reuptake inhibitor (SSRI) antidepressants, which represent the most used pharmacological therapy; physical exercise has also been shown to effectively counteract depression symptoms in rodents as well as in humans. While there is evidence that the antidepressant effect of fluoxetine requires its pro-neurogenic action, exerted by promoting proliferation, differentiation and survival of progenitor cells of the hippocampus, on the other hand fluoxetine exerts also neurogenesis-independent antidepressant effects by influencing the plasticity of the new neurons generated. Similarly, the antidepressant action of running also correlates with an increase of hippocampal neurogenesis and plasticity, although the gene pathways involved are only partially coincident with those of fluoxetine, such as those involved in serotonin metabolism and synapse formation. We further discuss how extra-neurogenic actions are also suggested by the fact that, unlike running, fluoxetine is unable to stimulate neurogenesis during aging, but still displays antidepressant effects. Moreover, in specific conditions, fluoxetine or running activate not only progenitor but also stem cells, which normally are not stimulated; this fact reveals how stem cells have a long-term, hidden ability to self-renew and, more generally, that neurogenesis is subject to complex controls that may play a role in depression, such as the type of neurogenic stimulus or the state of the local niche. Finally, we discuss how fluoxetine or running are effective in counteracting depression originated from stress or neurodegenerative diseases.

About 30% of medulloblastomas (MBs), a tumor of the cerebellum, arise from cerebellar granule cell precursors (GCPs) undergoing transformation following activation of the Sonic hedgehog (Shh) pathway. To study this process, we generated a new MB model by crossing Patched1 heterozygous (Ptch1 +/-) mice, which develop spontaneous Shh-type MBs, with mice lacking B-cell translocation gene 1 (Btg1), a regulator of cerebellar development. In MBs developing in Ptch1 +/- mice, deletion of Btg1 does not alter tumor and lesion frequencies, nor affect the proliferation of neoplastic precursor cells. However, in both tumors and lesions arising in Ptch1 +/- mice, ablation of Btg1 increases by about 25% the apoptotic neoplastic precursor cells, as judged by positivity to activated caspase-3. Moreover, although Btg1 ablation in early postnatal GCPs, developing in the external granule cell layer, leads to a significant increase of proliferation, and decrease of differentiation, relative to wild-type, no synergy occurs with the Ptch1 +/- mutation. However, Btg1 deletion greatly increases apoptosis in postnatal GCPs, with strong synergy between Btg1-null and Ptch1 +/- mutations. That pronounced increase of apoptosis observed in Ptch1 +/- /Btg1 knockout young or neoplastic GCPs may be responsible for the lack of effect of Btg1 ablation on tumorigenesis. This increased apoptosis may be a consequence of increased expression of protein arginine methyltransferase 1 (Prmt1) protein that we observe in Btg1 knockout/Ptch1 +/- MBs. In fact, apoptotic genes, such as BAD, are targets of Prmt1. Moreover, in Btg1-null MBs, we observed a two-fold increase of cells positive to CD15, which labels tumor stem cells, raising the possibility of activation of quiescent tumor cells, known for their role in long-term resistance to treatment and relapses. Thus, Btg1 appears to play a role in cerebellar tumorigenesis by regulating the balance between apoptosis and proliferation during MB development, also influencing the number of tumor stem cells.

This study investigated the effect of motor learning with informational feedback into response to anaerobic exercises with and without motor learning tasks in handball physical education university students. Participants were randomly divided into two groups: experimental group (EG, n = 10) and control group (CG, n = 10). Measurements of T-half test, 15-m and 30-m sprints, and ZIG-ZAG test were assessed in both groups before (T1), between (T2) a 4-week intervention program, and after (T3) an 8-week intervention program, which included agility and speed teaching with (EG) or without (CG) informational feedback (i.e., verbal instruction). The test-retest reliability for all tests was excellent, and the ICC ranged from 0.76 (ZIG-ZAG test) to 0.99 (Agility T test). The interday measurement error was clearly below 1% in all tests (CV range: 0.2–0.8). Time effects for the Agility T test (p = 0.012, ηp2 = 0.245) and the 15-m sprint (p = 0.035, ηp2 = 0.190) were found. For the Agility T test, a total interaction effect (p = 0.001, ηp2 = 0.380) and a partial interaction effect were calculated between T2 and T3 (p < 0.001, ηp2 = 0.603). A large effect size (d = 0.87) was observed in the EG from T2 to T3. The second relevant (d ≥ 0.5) effect size was calculated for the parameter sprint 30 m. The CG showed a significant sprint performance reduction from T2 to T3 (d = −0.60; parameter: sprint 30 m). All other effect sizes were less than 0.44. The ZIG-ZAG test revealed the largest main and partial effect sizes for all parameters. The EG showed the largest improvement (d = 2.00) between T2 and T3. The results demonstrate that motor learning with informational feedback improves performances of Agility T test, sprint, and ZIG-ZAG performance. It appears that a well-formulated verbal instruction may induce performance enhancement in young trainees in educational environment.

Since the 1980s, a Business District is located in the eastern area of Naples. The first pioneer studies carried out in this area showed that a significant variability of site amplification can be predicted due to the morphology of seismic bedrock and to the presence of vanishing lenses of peat. More recently, the seismic vulnerability of the New Law Court was assessed adopting the hypothesis of 1D conditions for the seismic response analysis. This paper aims at verifying the reliability of this assumption, evaluating the 2D seismic site response of a representative geological section. Geotechnical characterization of the soil deposits has been carried out by integrating the available experimental data with literature data. Two suites of accelerograms have been considered as input motions, representative of ‘near field’ and ‘far field’ seismic events. Equivalent linear and non-linear 2D analyses have been carried out through a finite element and a finite difference code, respectively. Results provide insights on the non-linear soil behaviour of peat and allow for recognizing the limits and advantages of both adopted approaches. Finally, the comparison between the results of 2D and 1D analyses allows for highlighting the effects of focalization of seismic waves on the amplification of the ground motion at the surface.

Response time is a fencing fundamental sensorimotor skill. Therefore, the aim of the current study was to examine the efficacy of a light-based electronic target in fencers, designed to measure and train this entity. Ninety-five fencers (M=53; F=42) were tested in regard to their response time, using a light-based electronic target, for three different attack types: simple attack, the lunge, and an attack following a 1.5-m thrust. All participants were divided into elite vs. novice fencers. Elite fencers had national and international rankings, and were again divided with regard to used weapon: épéeists (n=32; M=19; F=13) and foilists (n=30; M=13; F=17). Measurement was evaluated for validity/reliability, sensitivity/specificity, and correlation. Reliability was high for all attack types (ICC 0.94-0.96). Lower response times were found in males for two attack types with good sensitivity (81-93%)/specificity (50-91%) for all attack types. Elite fencers responded faster than novice fencers for all attack types (P

PC3/Tis21 is a transcriptional cofactor that inhibits proliferation in several cell types, including neural progenitors. Here, we report that PC3/Tis21 associates with HDAC1, HDAC4, and HDAC9 in vivo, in fibroblast cells. Furthermore, when HDAC1, HDAC4, or HDAC9 are silenced in fibroblasts or in a line of cerebellar progenitor cells, the ability of PC3/Tis21 to inhibit proliferation is significantly reduced. Overexpression of HDAC1, HDAC4, or HDAC9 in fibroblasts and in cerebellar precursor cells synergizes with PC3/Tis21 in inhibiting the expression of cyclin D1, a cyclin selectively inhibited by PC3/Tis21. Conversely, the depletion of HDAC1 or HDAC4 (but not HDAC9) in fibroblasts and in cerebellar precursor cells significantly impairs the ability of PC3/Tis21 to inhibit cyclin D1 expression. An analysis of HDAC4 deletion mutants shows that both the amino-terminal moiety and the catalytic domain of HDAC4 associate to PC3/Tis21, but neither alone is sufficient to potentiate the inhibition of cyclin D1 by PC3/Tis21. As a whole, our findings indicate that PC3/Tis21 inhibits cell proliferation in a way dependent on the presence of HDACs, in fibroblasts as well as in neural cells. Considering that several reports have demonstrated that HDACs can act as transcriptional corepressors on the cyclin D1 promoter, our data suggest that the association of PC3/Tis21 to HDACs is functional to recruit them to target genes, such as cyclin D1, for repression of their expression. J. Cell. Physiol. 232: 1696-1707, 2017. © 2016 Wiley Periodicals, Inc.

Purpose. To evaluate implant survival, peri-implant bone loss, and complications affecting fixed full-arch (FFA) restorations supported by implants with a knife-edge thread design and nanostructured, calcium-incorporated surface. Methods. Between January 2013 and December 2015, all patients referred for implant-supported FFA restorations were considered for enrollment in this study. All patients received implants with a knife-edge thread design and nanostructured calcium-incorporated surface (Anyridge®, Megagen, South Korea) were restored with FFA restorations and enrolled in a recall program. The final outcomes were implant survival, peri-implant bone loss, biologic/prosthetic complications, and “complication-free” survival of restorations. Results. Twenty-four patients were selected. Overall, 215 implants were inserted (130 maxilla, 85 mandible), 144 in extraction sockets and 71 in healed ridges. Thirty-six FFAs were delivered (21 maxilla, 15 mandible): 27 were immediately loaded and 9 were conventionally loaded. The follow-up ranged from 1 to 3 years. Two fixtures failed, yielding an implant survival rate of 95.9% (patient-based). A few complications were registered, for a “complication-free” survival of restorations of 88.9%. Conclusions. FFA restorations supported by implants with a knife-edge thread design and nanostructured, calcium-incorporated surface are successful in the short term, with high survival and low complication rates; long-term studies are needed to confirm these outcomes.

In the neurogenic niches – the dentate gyrus of the hippocampus and the subventricular zone (SVZ) adjacent to lateral ventricles – stem cells continue to divide during adulthood, generating progenitor cells and new neurons, and to self-renew, thus maintaining the stem cell pool. During aging the numbers of stem/progenitor cells in the neurogenic niches are reduced. The preservation of the neurogenic pool is committed to a number of antiproliferative genes, with the role of maintaining the quiescence of neural cells. The cyclin-dependent kinase inhibitor p16Ink4a, whose expression increases with age, controls the expansion of SVZ aging stem cells, since in mice its deficiency prevents the decline of neurogenesis in SVZ. No change of neurogenesis is however observed in the p16Ink4a-null dentate gyrus. Here we hypothesized that p16Ink4a plays a role as a regulator of the self-renewal of the stem cell pool also in the dentate gyrus, and to test this possibility we stimulated the dentate gyrus neural cells of p16Ink4a-null aging mice with physical exercise, a powerful neurogenic activator. We observed that running highly induced the generation of new stem cells in the p16Ink4a-null dentate gyrus, forcing them to exit from quiescence. Stem cells, notably, are not induced to proliferate by running in wild-type mice. Moreover, p16Ink4a-null progenitor cells were increased by running significantly above the number observed in wild-type mice. The new stem and progenitor cells generated new neurons, and continued to actively proliferate in p16Ink4a-null mice longer than in the wild-type after cessation of exercise. Thus, p16Ink4a prevents aging dentate gyrus stem cells from being activated by exercise. Therefore, p16Ink4a may play a role in the maintenance of dentate gyrus stem cells after stimulus, by keeping a reserve of their self-renewal capacity during aging.

Con l'Ordinanza n.1 del 27 novembre 2018 (in seguito, Ordinanza), il Commissario straordinario del Governo per la ricostruzione nei territori dell'isola di Ischia interessati dall'evento sismico del 21 agosto 2017 ha disposto la realizzazione degli studi di microzonazione sismica di III livello come definiti dagli "Indirizzi e criteri per la microzonazione sismica" approvati il 13 novembre 2008 dalla Conferenza delle Regioni e delle Province autonome di Trento e Bolzano, da utilizzare per la pianificazione e la progettazione esecutiva nelle aree maggiormente colpite dal sisma. Il presente documento corrisponde al report 8.2_4 "Relazione tecnico-scientifica finale" previsto dall'allegato A dell'allegato 2 dell'Ordinanza. In particolare questa relazione si riferisce all'attività A.8.2 "Monitoraggio delle attività di progetto per la verifica del raggiungimento dei risultati attesi" e riassume le modalità con le quali si è espletata l'attività in oggetto. La relazione integra e completa tutti i prodotti fino ad ora consegnati al Commissario. Essa si articola in un primo capitolo "Quadro riassuntivo delle attività" che sintetizza per fasi cronologiche le attività svolte e i prodotti correlati di volta in volta consegnati. Segue un secondo capitolo "Dati di base", in cui si riportano i dati relativi all'evento sismico del 21 agosto 2017 e si elencano le indagini pregresse e di nuova esecuzione, svolte dagli affidatari e dalla Struttura di supporto e coordinamento. Il terzo capitolo "Considerazione sui risultati degli studi di MS" concerne l'elaborazione dei dati di base e l'analisi e lo sviluppo degli studi di microzonazione sismica di III livello consegnati dagli affidatari. Il quarto capitolo "Considerazioni conclusive" sintetizza i punti di forza e le criticità emerse durante l'intero lavoro di coordinamento e supporto agli studi di microzonazione sismica nei territori di interesse.

Con l'Ordinanza n.1 del 27 novembre 2018 (in seguito, Ordinanza), il Commissario straordinario del Governo per la ricostruzione nei territori dell'isola di Ischia interessati dall'evento sismico del 21 agosto 2017 ha disposto la realizzazione degli studi di microzonazione sismica di III livello come definiti dagli "Indirizzi e criteri per la microzonazione sismica" approvati il 13 novembre 2008 dalla Conferenza delle Regioni e delle Province autonome di Trento e Bolzano, da utilizzare per la pianificazione e la progettazione esecutiva nelle aree maggiormente colpite dal sisma. Il presente documento corrisponde a uno dei report relativi alle attività A.4, "Stesura di protocolli e esecuzione di analisi ed elaborazioni" previste dall'allegato A dell'allegato 2 dell'Ordinanza. In particolare tale report si riferisce all'attività A.4.4 "Analisi numeriche di risposta sismica locale bidimensionale (2D), con elaborazione dei risultati in termini di fattori di amplificazione e spettri di risposta elastici in accelerazione". Il presente Report riguarda i risultati delle analisi geotecniche effettuate sui campioni prelevati, disturbati e indisturbati, dai sondaggi effettuati dagli affidatari nell'ambito dello studio di microzonazione sismica di III livello. Le analisi geotecniche sono state condotte dall'unità di supporto geotecnico del Dipartimento di Ingegneria Civile, Edile ed Ambientale dell'Università degli Studi di Napoli Federico II, in qualità di membri della Struttura di supporto e coordinamento individuata nell'art. 4 dell'allegato A dell'Allegato 2. Nella sezione Appendice, sono riportati i certificati finali delle prove fisiche e meccaniche dinamiche per ogni comune. Per quanto riguarda i risultati delle analisi numeriche bidimensionali, previste da progetto si rimanda ad una successiva integrazione del presente prodotto.

OBJECTIVE: To provide an overall estimate of the direct, indirect and total costs of irritable bowel syndrome (IBS) for the adult population of the European countries with universal healthcare coverage.MATERIALS AND METHODS: We searched MedLine and Scopus databases (up to September 2018) to identify the European studies that evaluated the economic impact of IBS. Mean annual direct, indirect and total per-capita IBS costs were estimated using random-effect single-group meta-analyses of continuous data. All analyses were stratified by payer category (governments, insurance, societal), and the results were expressed as summary mean and 95% CI.RESULTS: A total of 24 studies were included in the meta-analyses. Only two studies evaluated IBS costs in Italy. The pooled summary of direct IBS per-capita cost, obtained from 23 European datasets (n=15,157), was (sic)1837/year (95% CI: 1480-2195), with large differences across payers (from (sic)1183 to (sic)3358, in countries with publicly-funded and insurance-based health systems, respectively). The mean indirect cost, extracted from 13 datasets (n=3978), was (sic)2314/year (95% CI: 1811-2817), again with wide differences across payers. Finally, the meta-analysis estimating the total annual cost, based upon 11 European datasets (n=2757), yielded a summary estimate of (sic)2889/year (95% CI: 2318-3460) per patient, ranging from (sic)1602 (insurance-based health systems) to (sic)3909 (studies adopting a societal perspective).CONCLUSIONS: Considering a conservative estimate of 2,736,700 Italian adults affected by the syndrome, the minimum costs due to IBS in Italy - likely underestimated - range from 6 to 8 billion euro per year. Given the substantial economic burden for patients, healthcare systems and society, IBS should be included among the priorities of the public health agenda.

The Seismic Microzonation (SM) of Level 3 allows quantifying numerically seismic amplification effects on microzones, previously introduced after detailed geological reconstructions of local subsoil and geophysical-geotechnical characterization of bedrock and cover terrains. Major goals of the Level 3 SM studies are, indeed, the calculation and mapping of Amplification Factors (AF) at ground for different period intervals of engineering interest, and the defining of acceleration response spectra for each microzone. According to the Italian standards (Gruppo di Lavoro MS, 2008; SM Working Group, 2015), this can be achieved through 1D and 2D numerical simulations of the ground motion performed respectively on stratigraphic logs and on engineering-geological cross sections, with litothypes parametrized in terms of Vs and G/G0-? and D-? curves. The obtained results are basic for correct Urban Planning Strategies and Seismic Risk Mitigation Policies. It is here presented the case of Level 3 SM studies concerning the municipalities of Casamicciola Terme, Lacco Ameno and Forio (Island of Ischia, Naples, Italy), affected by the 21 August 2017 earthquake (Mw 3.9, http://iside.rm.ingv.it/en/event/16796811), which caused two victims and heavy damages to a large number of buildings. Ground acceleration was 0.28g at IV.IOCA station, EW component. Soon after the event, it was issued the OCDPC 476/2017 Decree by the Italian Civil Protection Head to promote studies on these territories for: 1) defining the engineering geological setting, and 2) collecting geophysical data (312 seismic noise measurements, 20 MASW tests, 4 passive 2D arrays), both preparatory for SM. The synthesis of borehole and literature data on the complex stratigraphy and volcano-tectonics of the island, coupled with results from the geophysical investigations, allowed to detect in a preliminary way the boundary depth between bedrock and cover units (Cavinato et al., 2018, with references therein). The following Decree 1/2018, by the Government Commissioner for reconstruction of damaged territories of the Island of Ischia, established purposes, time schedule (January-July 2019) and roles of participants to Level 3 SM studies on those areas. The studies, aimed at defining the AF and response spectra, were conducted by professionals, constantly and scientifically supported by a team of researchers from CNR (IGAG and ISMAR), INGV, and University of Naples "Federico II" (DICEA). In particular, the scientific community was responsible for the integration and validation of the study results.

Purpose. To present a digital technique for the fabrication of custom-made subperiosteal implants and to report on the survival and complication rates encountered when using these fixtures.Methods. The data used for this retrospective clinical study were derived from the medical records of five different private dental practices. Inclusion criteria were patients over the age of 60, treated with custom-made direct metal laser sintering (DMLS) titanium subperiosteal implants (Eagle-Grid®, BTK, Dueville, Vicenza) during a two-year period (2014-2015) and restored with fixed restorations; all enrolled patients needed to have complete pre- and postoperative clinical and radiographic documentation, with at least 2 years of follow-up. Exclusion criteria were smoking and bruxism. The main outcomes looked at were implant survival and complications.Results. Seventy patients (39 males and 31 females, aged 62-79 years) who had been treated with custom-made DMLS titanium subperiosteal implants were enrolled in this study. After 2 years of follow-up, three implants were lost due to recurrent, untreatable infections; the survival rate was therefore 95.8% (67/70 implants). Four patients reported pain/discomfort/swelling after implant placement; the incidence of immediate postoperative complications was therefore 5.7% (4/70 implants). During the follow-up period, one patient suffered from recurrent infections classified as a biologic complication; the incidence of biologic complications was therefore 1.4% (1/67 surviving implants). Finally, four patients experienced prosthetic problems with their implant-supported restorations during the provisional phase (fracture of the acrylic restoration) and two patients had ceramic chipping of the definitive restoration; the incidence of prosthetic complications was therefore 8.9% (6/67 surviving implants).Conclusions. Within the limits of the present study (limited follow-up time and low number of patients treated, retrospective design), the application of custom-made DMLS titanium subperiosteal implants showed satisfactory implant survival (95.8%) and low complication rates. Further studies are needed to confirm the positive outcomes found in this research.

La relazione scientifica riguarda i risultati derivanti dalle prime acquisizioni geofisiche (ERT, MASW, indagini sismiche a riflessione, misure di rumore sismico, Array) condotte a seguito del sisma del 21 agosto 2017 occorso sull'Isola di Ischia. Inoltre la relazione è corredata da sette carte geo-tematiche (carta geolitologica, carte geologico-tecniche, carte delle frequenze fondamentali, carte delle indagini) relative ai territori comunali di Casamicciola Terme, Lacco Ameno, Forio (NA). Vengono anche presentati i risultati preliminari di modellazioni numeriche bidimensionali di risposta sismica locale, relativi alla zona rossa di Casamicciola Terme.

Cell proliferation and differentiation are interdependent processes. Here, we have asked to what extent the two processes of neural progenitor cell amplification and differentiation are functionally separated. Thus, we analyzed whether it is possible to rescue a defect of terminal differentiation in progenitor cells of the dentate gyrus, where new neurons are generated throughout life, by inducing their proliferation and/or their differentiation with different stimuli appropriately timed. As a model we used the Tis21 knockout mouse, whose dentate gyrus neurons, as demonstrated by us and others, have an intrinsic defect of terminal differentiation. We first tested the effect of two proliferative as well as differentiative neurogenic stimuli, one pharmacological (fluoxetine), the other cognitive (the Morris water maze (MWM) training). Both effectively enhanced the number of new dentate gyrus neurons produced, and fluoxetine also reduced the S-phase length of Tis21 knockout dentate gyrus progenitor cells and increased the rate of differentiation of control cells, but neither factor enhanced the defective rate of differentiation. In contrast, the defect of terminal differentiation was fully rescued by in vivo infection of proliferating dentate gyrus progenitor cells with retroviruses either silencing Id3, an inhibitor of neural differentiation, or expressing NeuroD2, a proneural gene expressed in terminally differentiated dentate gyrus neurons. This is the first demonstration that NeuroD2 or the silencing of Id3 can activate the differentiation of dentate gyrus neurons, complementing a defect of differentiation. It also highlights how the rate of differentiation of dentate gyrus neurons is regulated genetically at several levels and that a neurogenic stimulus for amplification of neural stem/progenitor cells may not be sufficient in itself to modify this rate.

Scope.To demonstrate guided implant placement and the application of fixed, implant-supported prosthetic restorations with a fully digital workflow.Methods.Over a 2-year period, all patients with partial edentulism of the posterior maxilla, in need of fixed implant-supported prostheses, were considered for inclusion in this study. The protocol required intraoral scanning and cone beam computed tomography (CBCT), the superimposition of dental-gingival information on bone anatomy, surgical planning, 3D-printed teeth-supported surgical templates, and modelling and milling of polymethylmethacrylate (PMMA) temporaries for immediate loading. After 3 months, final optical impression was taken and milled zirconia frameworks and 3D-printed models were fabricated. The frameworks were veneered with ceramic and delivered to the patients.Results.Fifteen patients were selected for this study. The surgical templates were stable. Thirty implants were placed (BTK Safe®, BTK, Vicenza, Italy) and immediately loaded with PMMA temporaries. After 3 months, the temporaries were replaced by the final restorations in zirconia-ceramic, fabricated with a fully digital process. At 6 months, none of the patients reported any biological or functional problems with the implant-supported prostheses.Conclusions.The present procedure for fully digital planning of implants and short-span fixed implant-supported restorations has been shown to be reliable. Further studies are needed to validate these results.

PC3/Tis21 is a transcriptional cofactor that inhibits proliferation in several cell types, including neural progenitors. Here, we report that PC3/Tis21 associates with HDAC1, HDAC4, and HDAC9 in vivo, in fibroblast cells. Furthermore, when HDAC1, HDAC4, or HDAC9 are silenced in fibroblasts or in a line of cerebellar progenitor cells, the ability of PC3/Tis21 to inhibit proliferation is significantly reduced. Overexpression of HDAC1, HDAC4, or HDAC9 in fibroblasts and in cerebellar precursor cells synergizes with PC3/Tis21 in inhibiting the expression of cyclin D1, a cyclin selectively inhibited by PC3/Tis21. Conversely, the depletion of HDAC1 or HDAC4 (but not HDAC9) in fibroblasts and in cerebellar precursor cells significantly impairs the ability of PC3/Tis21 to inhibit cyclin D1 expression. An analysis of HDAC4 deletion mutants shows that both the amino-terminal moiety and the catalytic domain of HDAC4 associate to PC3/Tis21, but neither alone is sufficient to potentiate the inhibition of cyclin D1 by PC3/Tis21. As a whole, our findings indicate that PC3/Tis21 inhibits cell proliferation in a way dependent on the presence of HDACs, in fibroblasts as well as in neural cells. Considering that several reports have demonstrated that HDACs can act as transcriptional corepressors on the cyclin D1 promoter, our data suggest that the association of PC3/Tis21 to HDACs is functional to recruit them to target genes, such as cyclin D1, for repression of their expression. J. Cell. Physiol. 232: 1696-1707, 2017. © 2016 Wiley Periodicals, Inc.

In the frame of a research project involving a private collection of artworks a panel painting representing the Nursing Madonna (Madonna del latte) was studied by means of scientific examination.The Department of Chemistry and Industrial Chemistry (DCCI) of the University of Genoa carried out non-invasive exams, combining imaging techniques with analytical analyses.Infrared reflectography (IRR), infrared false colour (IRFC), UV fluorescence (UVF), X-ray fluorescence (XRF) and reflectance spectroscopy in the visible range (vis-RS) were used to analyse the painting palette thus obtaining more information on a possible creation date of the painting.Some of the most interesting results are the identification of a freehand underdrawing and the usage of lead white, cinnabar, Fe-based pigments for yellows and browns and Cu-based pigments for blue and green colours.The scientific results, as well as historical researches allow the hypothesis that the Madonna del latte was authored in the early 16th century by a Florentine artist, probably a scholar of Baccio della Porta.

Restricted Boltzmann Machines (RBMs) and autoencoders have been used-in several variants-for similar tasks, such as reducing dimensionality or extracting features from signals. Even though their structures are quite similar, they rely on different training theories. Lately, they have been largely used as building blocks in deep learning architectures that are called deep belief networks (instead of stacked RBMs) and stacked autoencoders. In light of this, the student has worked on this thesis with the aim to understand the extent of the similarities and the overall pros and cons of using either RBMs, autoencoders or denoising autoencoders in deep networks. Important characteristics are tested, such as the robustness to noise, the influence on training of the availability of data and the tendency to overtrain. The author has then dedicated part of the thesis to study how the three deep networks in exam form their deep internal representations and how similar these can be to each other. In result of this, a novel approach for the evaluation of internal representations is presented with the name of F-Mapping. Results are reported and discussed.

In this thesis I demonstrated how a singular neural network can potentially represent the set of more latent neural circuits, able to execute different functions, based on an input encoding so to reprogram their functionality. Such programmable structure, in passing from one behavior to another, does not require further learning procedures, nor any structural modifications. This is ideal to execute quick and reversible transitions such as the ones showed in biological organisms’ behaviors.

An accurate measurement of dynamic soil properties is essential to predict the nonlinear soil behavior under seismic loading conditions. This paper presents a database of cyclic and dynamic laboratory tests carried out after the 2016-2017 Central Italy Earthquake sequence, as part of the seismic microzonation studies in the area. The database consists of experimental results obtained on 79 samples investigated by means of dynamic resonant column tests, cyclic torsional shear tests or cyclic double specimen direct simple shear tests. The dynamic soil behavior is analyzed with reference to the small-strain wave velocity and damping ratio and to the modulus reduction and damping ratio curves. Experimental data are compared with the most widely used predictive models to underline the peculiarities of the investigated soils. Finally, a predictive model is calibrated to capture the nonlinear behavior of typical fine-grained soils from Central Italy.