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The fourth industrial revolution, also referred to as Industry 4.0, is a disruptive transformation process aimed which, by means of digital technologies, is substantially innovating the value creation processes in all industry contexts. With such premise, industry 4.0 is in particular expected to have a substantial impact on the maritime transport and shipping sectors, where smart ships and autonomous vessels are expected to be the building blocks of a new interconnected maritime ecosystem. The application of Industry 4.0 principles to the shipping domain (Shipping 4.0) has thus raised a scientific debate about the efficiency, sustainability, and safety of maritime transport. Recent researches, however, mostly focus on technological aspects, neglecting the issues related to the current dynamics of value creation in the shipping industry. This paper addresses such topic by discussing the shortfalls of the current industrial practice and the existing gap with the next generation concept

Tumors are composed of proliferating cells that invade healthy tissue and grow over time. Even though it is still unclear, it is a common opinion that the cells of origin should possess a proliferative capacity (Blanpain, 2013; Visvader, 2011). Particularly for brain cancers, the transition of neural progenitors to differentiated postmitotic neurons is considered irreversible in physiological and pathological conditions. Therefore, postmitotic neurons have not been considered as suitable cell of origin for brain cancer. Here, we show that neurons reprograming may occur upon Shh activation leading to medulloblastoma (MB) formation in vivo. Human SHH medulloblastoma (MB) is a brain tumor affecting adults and infants that is thought to originate from cerebellar granule neuron progenitors. Notably, several groups have shown that Shh pathway activation (SmoM2 overexpression) in mouse granule neuron progenitors is able to induce Shh MB (Schuller et al., 2008; Z.-J. Yang et al., 2008). These progenitors are present in infants and newborn mice, but they seem to be absent in adult humans and mice (Biran, Verney, & Ferriero, 2012; Marzban et al., 2014; Z.-J. Yang et al., 2008). Furthermore, it was recently discovered that the two different forms of SHH MB are distinguished by different transcriptome/methylome levels suggesting that the adult SHH MB may originate from a different cell of origin (Cavalli et al., 2017; Kool et al., 2014). Relying on these data, we take advantage of a conditional Cre-Lox recombination system to recapitulate the human adult medulloblastoma pathogenesis in mice, demonstrating that cerebellar post-migratory mature granule neurons upon SmoM2 overexpression can dedifferentiate and give rise to SHH MB in vivo. Moreover, human adult patients present inactivating mutations of the chromatin reader BRPF1 that are associated with SMO mutations and absent in pediatric and adolescent patients. Here we found that truncated BRPF1 protein, as found in human adult patients, is able to induce medulloblastoma in adult mice upon SmoM2 activation. Notably, gene expression profiling on our samples allowed to associate ?cerebellar granule progenitors-derived MB? with the human infant form while ?truncated BRPF1-induced tumors? clustered with human adult SHH MB. Furthermore, as previously described by Kool et al., 2014, human adult SHH MB is characterised by the copresence of p-AKT and p-S6, compared to the human infant SHH MB that are positive for either p- AKT or p-S6 and always in a mutually exclusive way. Truncated BRPF1-induced tumors are double positive for p-AKT and p-S6, similarly to adult patients, while cerebellar granule progenitors derived MB present only p-S6. Furthermore, to define the contribution of chromatin changes in granule neurons dedifferentiation in response to Shh activation, we profiled changes in chromatin accessibility by ATAC-seq analysis on mice cerebella. SmoM2 overexpression changed the epigenetic landscape of granule neurons, enriching the number of open chromatin regions 12 associated with stem/progenitor-like genes. Moreover, the cooperation between truncated BRPF1 and SmoM2 in reshaping the chromatin arrangement of granule neurons was explored applying ATAC-seq on differentiated human cerebellar neurons derived from neuroepithelial cells. ATAC-seq analysis pointed out a synergistic mechanism between SmoM2 and truncated BRPF1 in modifying the epigenetic landscape of postmitotic neurons, increasing the chromatin accessibility of super-enhancers, associated with stemness and chromatin organization/modification genes. Our novel model of cancer development could explain the human SHH medulloblastoma onset in adult individuals where granule neuron progenitors are no more present. For these reasons, we strongly believe that our model configures as an important starting point for a new field in cancer and stem cell biology focusing on the study of mechanisms driving tumorigenesis in postmitotic cells.

The most recent data obtained at the Montalbano Jonico succession (MJS), in the interval including the Marine Isotope Stage (MIS) 19, document the occurrence of numerous chronostratigraphic constraints and paleoenvironmental events contributing to the knowledge of a crucial time through the Lower-Middle Pleistocene transition, characterised by major modifications of the Earth’s climate system. Marine and terrestrial biologic data-sets (pollen, ostracods, benthic and planktonic foraminifera, coccolithophores, teleostean fishes, mollusks) are compared with the high resolution astronomically-tuned benthic oxygen isotope curve in order to provide accurate paleonvironmental reconstruction and acquire additional climatostratigraphic and biostratigraphic constraints within a chronostratigraphic framework which also includes the 40Ar/39Ar ages of three volcaniclastic layers. Environmental and climatic events (e.g. Termination IX, substages 19.3, 19.2, and 19.1, maximum flooding and climate optimum, maximum depth) highlight a succession of clear paleoenvironmental changes close to MIS 19, showing a remarkable correspondence between the response of marine and terrestrial proxies. Such changes have stratigraphic implication and high potential of correlation as they evidence wide scale climate changes, stressing the tight interconnection between the Mediterranean region and North Atlantic Ocean. Based on these results the MJS reveals to be an excellent candidate for the Lower-Middle Pleistocene Subseries boundary. In fact, at present the MJS fully meets the requirements indicated by Remane et al. (1996) for a GSSP selection with the sole exception that a paleomagnetic signal is missing. 10Be analyses are in progress and should enhance the already rich documentation of several independent age-significant elements, contributing to the recent critical discussion on the significance of the magnetic signal at the Matuyama-Brunhes boundary as well as its role as a primary marker for the Middle Pleistocene GSSP definition.

Metodo per la realizzazione di sensori elettrochimici con materiali recuperati da dispositivi di memorizzazione di scarto, quali CD e DVD

The variability of the reticulum pattern, ornamentation and outline of the Urocythereis populations of the La Strea Bay has been analysed. The results show that the shell features of the form U. distinguenda (Neviani, 1928) (= U. oblonga Brady, 1866) have to be included within the high variability range of U. margaritifera (G.W. Müller, 1894). Consequently, it is suggested that in the upper infralittoral waters of the inlet two (and not three, as stated in previous investigations) Urocythereis species presently live. A second form, displaying a relatively low variability, has been described as new species, U. ilariae sp. nov.

Urocythereis ilariae sp. nov. urn:lsid:zoobank.org:act: 607A810F-773C-4F8F-91E7-D2EB5223CB7D Figs 2B; 3 G–H; 4G–H; 5G–H; 6G–H; 14; 18A–J; 19A–C, E–J Urocythereis favosa (Roemer) n. ssp. Bassiouni, 1965: pl. 40, figs 8–9. Urocythereis favosa (Roemer) subsp. – Wouters 1973: 385, pl. 2, fig. 7. Urocythereis sp. – Bonaduce, Ciampo & Masoli 1976: 46, pl. 22, fig. 9. ? Urocythereis sp. – Athersuch 1977: pl. 17, fig. 2. Urocythereis aff. U. favosa (Roemer) – Arbulla, Pugliese & Russo 2001: fig. 3t. ? Urocythereis sp.1 – Barra 1997: 82, pl. 4, fig. 6. Urocythereis sp.1 – Aiello et al. 2006: tables 3, 10. — Aiello, Barra & Parisi 2013: fig. 1d. Diagnosis A large reticulate species of Urocythereis, subrectangular in lateral view, inflated-ovate in dorsal view. Reticulum with large polygonal-rounded, frequently coalescing, large fossae separated by broad muri. In the anteroventral area the muri form distinct riblets running parallel to the margin. Etymology In honour of our friend and collegue Ilaria Mazzini, in recognition of her important contribution to ostracodology. Type material (4 carapaces, 43 valves: 29 adults and 14 juveniles) Holotype IONIAN SEA: ABMC 2014 /03 Paratypes IONIAN SEA: ABMC2 014/026–036, ABMC 2014/038, ABMC 2014/042, ABMC 2014/044, ABMC 2014/046–049, ABMC 2014/063–064, ABMC 2014/069, ABMC 2014/072–073, ABMC 2014/080, ABMC 2014/097–103, ABMC 2014/120–135. Stratum typicum Recent. Locus typicus La Strea Bay (Porto Cesareo Lagoon), Southern Italy, Ionian Sea, sampling station E4, 17°54'25" N, 40°15'59" E, depth 1.5 m bsl. Description Measurements (holotype): LV: L = 0.85 mm, H = 0.44 mm (Fig. 18A). Large (L = 0.85–0.90 mm) species of Urocythereis, characterized by large fossae and strongly developed muri, subrectangular in lateral view, inflated-ovate in dorsal view. Valves strongly calcified and thick. Dorsal margin gently, unevenly convex, ventral margin weakly sinuous; anterior end broadly rounded, denticulate in the lower part; upper part of the posterior margin concave, lower part of the posterior margin convex, variably denticulate, forming short blunt caudal process located below mid-height. Maximum height at anterior cardinal angle, greatest length below mid-height. Surface of valves coarsely reticulate. Fossae, showing subrounded or irregular shape, coalesce, especially in marginal areas, forming both multiple anastomized elongated fossae and deep sulci parallel to margin. The corresponding muri tend to form a system of concentric riblets. Marginal rim starts from anterior part of dorsal margin, behind eye tubercle (Fig. 19C), and ends in posteroventral angle. Second riblet, constantly well developed, runs parallel to margin of valve except posterior end. This ocular riblet is connected with eye tubercle and rises above dorsal margin. Marginal rim and second riblet not connected. Third riblet, irregularly developed, delimits anteriorly the reticulum stricto sensu from subocular area to posterior part of ventral area and is connected with second riblet anteriorly, at mid height, through single radial murus; in the ventral area second and third riblets converge and, in lateral view, they seem apparently to be connected, but ventral view (Fig. 19A) shows they remain separate. The fossae between second and third riblet mainly anastomized. Fourth riblet fully part of reticulum, and shows a rather regular parallel trend only in anterocentral area. Surface of central area irregularly reticulate with subrounded/polygonal fossae with a low degree of anastomosis. Conversely, fossae located in proximity of caudal process coalesce following a longitudinal trend. Rare specimens show celation, never fully developed. Muri smooth, not papillate (Fig. 19E). Hinge holamphidont (sensu Scott 1961): in left valve posterior hinge socket elongate and curved; anterior element formed by ovate-rounded (or elongate) tooth and elongate socket; median bar smooth; its posterior thickening forms, in some cases, barely defined toothlet; right valve hinge complementary, with faintly crenulate teeth (Figs 18 I–J; 19G–J). Inner lamella, marginal pore canals and muscle scar pattern (Fig. 19F) characteristic of genus (details in Athersuch 1977). Distribution The species occurs in the Recent of the Mediterranean: Gulf of Naples (Bassiouni 1965), Sardinia (Arbulla et al. 2001), South Adriatic Sea (Bonaduce et al. 1976) and possibly Libya (see section Remarks); it has previously been recorded in fossil associations from the Tyrrhenian (upper Pleistocene) of Tunisia only (Wouters 1973). Distribution data are summarized in Fig. 14. Remarks U. ilariae sp. nov. has previously been assigned to U. favosa (Bassiouni 1965; Wouters 1973), type species of the genus Urocythereis (neotype figured by Athersuch 1977). The reticulation of U. favosa differs from that of U. ilariae sp. nov. in the different style of fossal anastomosis. This is mostly evident, for example, in the anterodorsal zone, where the continuous depressed area formed by the fossal pattern C1-C2/B1-B4 is present in U. ilariae sp. nov. and absent in the Pliocene species. The shell characters of U. exedata, described by Uliczny (1969) as a subspecies of U. favosa (SEM micrographs in Mostafawi & Matzke-Karasz 2006), show a close resemblance to those of U. ilariae sp. nov., especially in the structure of the ocular riblet, homologous to Bradleya ’s “ocular ridge” (Benson 1972). The Pliocene species probably represents an ancestor of the living form. The two species differ in some reticulum features. In the anteroventral area of U. ilariae sp. nov. the third and the fourth riblets are connected ventrally and anteriorly; consequently they delimit the merged C fossae, forming an anteroventral furrow enclosed by muri. Conversely, in U. exedata the anteroventral area is characterized by a segment of the third riblet encircled by an elongated ring made up of B and C anastomized fossae, anteriorly and ventrally connected. In the anterodorsal area of U. ilariae sp. nov., the third concentric riblet is more or less developed in different specimens (Figs 2B; 18D, F), while in U. exedata in the anterodorsal area the fossae of the B group coalesce with C and D fossae, the muri follow a radial trend and consequently the third concentric riblet is virtually absent. The assignment of the North-African form, figured by Athersuch (1977) as Urocythereis sp. and by Barra (1997) as Urocythereis sp. 1, to U. ilariae sp. nov. needs further investigation. At the current state of knowledge we are inclined to interpret the morphological differences between the central Mediterranean species and the Lybian deme as the beginning of an allopatric speciation. Urocythereis margaritifera (G.W. Müller, 1894) Figs 2A; 3 A–F; 4A–F; 5A–F; 6A–F; 16A–K; 17A–J; 19D Cythere oblonga Brady, 1866: 353, pl. 59, figs 5a–d (non C. oblonga M’Coy, 1844). Cythereis margaritifera G.W. Müller, 1894: 368, pl. 32, figs 26, 29, 32, 35–37. Cythereis (Auris) distinguenda Neviani, 1928: 105 (synonymy only) (non p. 105 description and pl. 2, figs 91–93). Urocythereis margaritifera alba Uliczny, 1969: 65, pl. 15, fig. 9. Urocythereis sp. Athersuch, 1977: pl. 17, fig. 5. Urocythereis sp. 2 Barra, 1997: 82-83, pl. 4, fig.8. Urocythereis sp. 3 Barra, 1997: 83, pl. 4, fig. 11. Hemicythere (Urocythereis) margaritifera – Ruggieri 1953: 94, pl. 6, fig. 1. Urocythereis britannica Athersuch – Kubanc 1995: 32–33, pl. 8, figs 4a–b. Urocythereis crenulosa (Terquem) – Mostafawi & Matzke-Karasz 2006: pl. 6, fig. 9 (non pl. 8, fig. 1; non Cythere crenulosa Terquem, 1878). Urocythereis distinguenda – Athersuch 1977: 257, 259, pl. 7, figs 1–6; pl. 8, figs 1–6; pl. 9, figs 1–5; pl. 12, figs 5–6; figs 3c–d. — Athersuch 1979: fig. 2.19. — Aiello et al. 2006: tabs. 3, 7, 10. — Aiello, Barra & Parisi 2013: fig. 1b. Urocythereis favosa (Roemer) – Barbeito-Gonzalez 1971: 279, pl. 13, figs 1b, 3b, 4b, 6b, pl. 46, figs 24- 27 (non pl. 13, figs 2b, 5b, pl. 46, figs 28–29). — Doruk 1974: pl. 38, fig. 3, pl. 40, figs 1–3 (non pl. 34, figs 1-2, pl. 38, figs 1-2). — Puri 1974: pl. 13, fig. 3. — Tunoglu 1999: pl. 7, fig. 1. Urocythereis aff. U. favosa – Bonaduce, Ciampo & Masoli 1976: 45, pl. 22, fig. 8 (sic fig. 7). ? Urocythereis favosa – Triantaphyllou, Tsourou, Koukousioura & Dermitzakis 2005: pl. 3, fig 11. Urocythereis margaritifera – Athersuch 1977: 260, 262, pl. 12, figs 1–4; pl. 13, figs 1–6; pl. 14, figs 1–5; figs 3e–f. — Tsapralis 1981: 100, pl. 1, fig. 1. — Lachenal 1989: 175–176, pl. 3, fig. 14. — Kubanç 1995: 31–32, pl. 8, figs 3a–c. — Aiello et al. 2006: tabs. 3, 5. — Perçin-Paçal & Balkis 2012: pl. 2, fig. 3. — Aiello, Barra & Parisi 2013: fig. 1a. ? Urocythereis margaritifera – Aranki 1987: 72, pl. 19, figs 5–7. — Stancheva 1989: pl. 2, fig. 9. — Şafak, Avşar & Meriç 1999: pl. 3, fig. 12. Urocythereis cf. U. margaritifera – Arbulla, Pugliese & Russo 2001: fig. 3s. Urocythereis ? margaritifera – Aiello, Barra & Parisi 2013: fig. 1c. Urocythereis margaritifera alba – Breman 1976: 63-64, pl. 9, fig. 124. — Aiello, Barra, De Pippo & Donadio 2012: pl. 2, fig. 8. ? Urocythereis margaritifera alba – Uffenorde 1972: 79, pl. 8, fig. 9. Urocythereis margaritifera margaritifera – Uliczny 1969: 65, pl. 15, fig. 8. ? Urocythereis margaritifera margaritifera – Sissingh 1972: 128, pl. 10, fig. 8. Urocythereis seminulum (Seguenza) – Şafak, Avşar & Meriç 1999: pl. 3, fig. 11. Urocythereis sp. – Mostafawi, 1994: 107, pl. 7, fig. 6. Distribution The species is widely distributed in the infralittoral waters of the Eastern Mediterranean (Brady 1866; Barbeito-Gonzalez 1971; Doruk 1974; Athersuch 1977, 1979; Kubanç 1995; Tunoglu 1999; Perçin- Paçal & Balkis 2012), the Tyrrhenian Sea (G.W. Müller 1894; Puri 1974) and the southern Mediterranean (Athersuch 1977; Lachenal 1989; Barra 1997). Recordings from the Black Sea are uncertain: the specimen figured by Stancheva (1989) is a young instar, and Schornikov (1969) reported Müller’s original drawings. The species is present in the southern part of the Adriatic Sea; the findings in the central and northern Adriatic are doubtful (Uffenorde 1972; Bonaduce et al. 1976; Breman 1976). Fossil specimens have been reported from the Upper Pleistocene–Holocene of the Gulf of Gabès (Lachenal 1989), the Pleistocene of Southern Italy (Ruggieri 1953; Aiello et al. 2012), Zakynthos (Tsapralis 1981), the Northern Peloponnesus (Mostafawi 1994) and, possibly, Rhodes (Sissingh 1972) and from the Pliocene of Cephalonia (Uliczny 1969). Distribution data are summarized in Fig. 14. The presence of the species in Miocene sediments (Şafak et al. 1999) has to be confirmed by further studies. Remarks The analysis of the shell features of the Urocythereis population in the La Strea Bay and comparisons with the literature have convinced us that U. margaritifera and U. distinguenda (= U. oblonga) are two morphotypes of the same species. In particular, we consider the latter “species” as the celated variation of the former. Celation is not expressed homogeneously on the valves in all the specimens; consequently, also “transitional” shells show different morphs. The original illustration by Müller (1894: pl. 32, fig. 26) shows anteroventral fossae horizontally merged; the lectotype reported by Athersuch (1977: pl. 13, fig. 2) and the Libyan specimen figured by Barra (1997, as U. sp. 2) shows the same feature. Presently, we do not regard this character as diagnostic, due to the observed variability. Athersuch (1977) figured some appendages, including the right copulatory appendage, of U. distinguenda and the left copulatory appendage of U. margaritifera. Regarding the discrimination of the two species, the author stated that in U. margaritifera the ductus ejaculatorius is short and is contained within the area of the appendage, whereas in U. distinguenda the duct is much longer and passes beyond the ventral margin. Examination of Athersuch’s illustrations (figs 4.d; 5.i) and a comparison with Müller’s drawing of the male copulatory appendage of Cythereis margaritifera (pl. 32, fig. 32) show that only very subtle differences are present and they represent, in our opinion, intraspecific variations. The maximum mesh size is reached in the subspecies Urocythereis margaritifera alba Uliczny, 1969. This form, in which celation is not developed, does not occur in the La Strea Bay. In some specimens the SEM micrographs revealed a feeble trace of the muri underlying the secondary calcification, as shown in Fig. 15. The comparison of this hidden reticulation with the specimens figured by Uliczny (1969), Breman (1976) and Aiello et al. (2012) suggests that U. m. alba is a non-celate morphotype of U. margaritifera. The North Adriatic form figured by Uffenorde (1972) (very similar to the Pliocene specimen figured by Şafak et al. 1999 as U. margaritifera) shows some tiny differences in the reticulation pattern and the assignment to U. margaritifera is queried. The Libyan form figured by Athersuch (1977: pl. 17, fig. 5) as U. sp. and by Barra (1997) as U. sp. 3 fits the U. margaritifera morph c (Fig. 17E) well. The left valve, figured by Aranki (1987) from the western Mediterranean shallow waters, shows some minor differences in the reniform outline and in some details of the reticulum. The relationships between Mediterranean and Atlantic forms (i.e., between U. margaritifera and U. britannica, frequently reported as U. oblonga) need further investigations. Ruggieri (1953) hypothesized that U. favosa and U. margaritifera might be conspecific, the latter species representing a subspecies of the former. In spite of the similarity of the two forms, some features of the reticulum seem to allow a separation of the two species. In U. favosa (neotype figured in Athersuch 1977) the fossae B3 and B4 are merged, as well as C3 and C4; in U. margaritifera they are distinct; in U. favosa the fossae D2-D1 and α4 coalesce while in U. margaritifera they are distinct. In the caudal group the fossa Cg 4 in U. margaritifera is separate, whereas in U. favosa the arrangement of the fossae is similar to that in U. ilariae sp. nov. In the La Strea Bay, and possibly in the Recent of the Mediterranean, U. favosa s.s. is not recorded and we prefer to retain them as separate species. Some Urocythereis spp. from the Pliocene of Rhodes have been described by Terquem (1878) and figured by Mostafawi (1989). They are distinct from U. margaritifera in some characters of the reticulum. By contrast, the specimen from Cephalonia figured by Mostafawi & Matzke-Karasz (2006) as U. crenulosa fits well with some specimens of U. margaritifera from Porto Cesareo. The Atlantic forms reported as U. britannica and (erroneously) as U. oblonga (e.g., Guillaume et al. 1985; Ruiz et al. 2006) show a high variability and a complex affinity with U. margaritifera and U. favosa and they have not been considered in the present study.