Problems Affecting Labor

Much experimental work has been devoted in comparing the folding behavior of proteins sharing the same fold but different sequence. The recent design of proteins displaying very high sequence identities but different 3D structure allows the unique opportunity to address the protein-folding problem from a complementary perspective. Here we explored by ℙ-value analysis the pathways of folding of three different heteromorphic pairs, displaying increasingly high-sequence identity (namely, 30%, 77%, and 88%), but different structures called G A (a 3-α helix fold) and G B (an α/β fold). The analysis, based on 132 site-directed mutants, is fully consistent with the idea that protein topology is committed very early along the pathway of folding. Furthermore, data reveals that when folding approaches a perfect two-state scenario, as in the case of the G A domains, the structural features of the transition state appear very robust to changes in sequence composition. On the other hand, when folding is more complex and multistate, as for the G Bs, there are alternative nuclei or accessible pathways that can be alternatively stabilized by altering the primary structure. The implications of our results in the light of previous work on the folding of different members belonging to the same protein family are discussed

InSAR Time Series Analysis of Natural and Anthropogenic Coastal Plain Subsidence: The Case of Sibari (Southern Italy)

We applied the Small Baseline Subset multi-temporal InSAR technique (SBAS) to two SAR datasets acquired from 2003 up to 2013 by Envisat (ESA, European Space Agency) and COSMO-SkyMed (ASI, Italian Space Agency) satellites to investigate spatial and temporal patterns of land subsidence in the Sibari Plain (Southern Italy). Subsidence processes (up to ~20 mm/yr) were investigated comparing geological, hydrogeological, and land use information with interferometric results. We suppose a correlation between subsidence and thickness of the Plio-Quaternary succession suggesting an active role of the isostatic compensation. Furthermore, the active back thrusting in the Corigliano Gulf could trigger a flexural subsidence mechanism even if fault activity and earthquakes do not seem play a role in the present subsidence. In this context, the compaction of Holocene deposits contributes to ground deformation. Despite the rapid urbanization of the area in the last 50 years, we do not consider the intensive groundwater pumping and related water table drop as the main triggering cause of subsidence phenomena, in disagreement with some previous publications. Our interpretation for the deformation fields related to natural and anthropogenic factors would be a comprehensive and exhaustive justification to the complexity of subsidence processes in the Sibari Plain

Volcanic spreading forcing and feedback in geothermal reservoir development, Amiata Volcano, Italia

We made a stratigraphic, structural and morphologic study of Amiata Volcano in Italy. We find that the edifice is dissected by intersecting grabens that accommodate the collapse of the higher sectors of the volcano. In turn, a number of compressive structures and diapirs exist all around the margin of the volcano. These structures create an angular drainage pattern, with stream damming and captures, and a set of lakes within and around the volcano. We interpret these structures as the result of volcanic spreading of the edifice of Amiata onto its weak substratum, formed by the late Triassic evaporites (Anidriti of Burano) and the Middle-Jurassic to Early-Cretaceous clayey chaotic complexes (Ligurian Complex). Regional doming created a slope in the basement forcing the outward flow and spreading of the ductile layers below the volcano. We model the dynamics of spreading with a scaled lubrication approximation of the Navier Stokes equations, and numerically study a solution. In the model we include simple functions for volcanic deposition and surface erosion that change the topography over time. Scaling indicates that spreading at Amiata could still be active. The numerical solution shows that, as the central part of the edifice sinks into the weak basement, diapiric structures of the underlying formations form around the base of the volcano. Deposition of volcanic rocks within the volcano and surface erosion away from it both enhance spreading. In addition, a sloping basement may constitute a trigger for the formation of trains of adjacent diapirs. Finally, we observe that volcanic spreading has created ideal heat traps that constitute todays’ exploited geothermal fields at Amiata. Normal faults generated by volcanic spreading, volcanic conduits, and direct contact between volcanic rocks (which host an extensive fresh-water aquifer) and the rocks of the geothermal field, constitute ideal pathways for water recharge during vapour extraction for geothermal energy production. We think that volcanic spreading could maintain faults in a critically stressed state, facilitating the occurrence of triggered seismicity

Where Are You Going, Nephrology? Considerations on Models of Care in an Evolving Discipline

Nephrology is a complex discipline, including care of kidney disease, dialysis, and transplantation. While in Europe, about 1:10 individuals is affected by chronic kidney disease (CKD), 1:1000 lives thanks to dialysis or transplantation, whose costs are as high as 2% of all the health care budget. Nephrology has important links with surgery, bioethics, cardiovascular and internal medicine, and is, not surprisingly, in a delicate balance between specialization and comprehensiveness, development and consolidation, cost constraints, and competition with internal medicine and other specialties. This paper proposes an interpretation of the different systems of nephrology care summarising the present choices into three not mutually exclusive main models (“scientific”, “pragmatic”, “holistic”, or “comprehensive”), and hypothesizing an “ideal-utopic” prevention-based fourth one. The so-called scientific model is built around kidney transplantation and care of glomerulonephritis and immunologic diseases, which probably pose the most important challenges in our discipline, but do not mirror the most common clinical problems. Conversely, the pragmatic one is built around dialysis (the most expensive and frequent mode of renal replacement therapy) and pre-dialysis treatment, focusing attention on the most common diseases, the holistic, or comprehensive, model comprehends both, and is integrated by several subspecialties, such as interventional nephrology, obstetric nephrology, and the ideal-utopic one is based upon prevention, and early care of common diseases. Each model has strength and weakness, which are commented to enhance discussion on the crucial issue of the philosophy of care behind its practical organization. Increased reflection and research on models of nephrology care is urgently needed if we wish to rise to the challenge of providing earlier and better care for older and more complex kidney patients with acute and chronic kidney diseases, with reduced budgets

Towards a Geological Information System: the CARGeo System and the Regione Lombardia Geological Database.

In the framework of the national mapping program «CARGNew Italian Geological Map at 1:50.000 scale», Regione Lombardia is generating a detailed map (1:10.000 scale) of its territory. Surveying criteria have been carefully defined in order to produce homogeneous geological maps: geological survey has been performed at the 1:10.000 scale, and data have been stored in a GIS-oriented database. The detailed survey scale improved the geological knowledge: the new maps represent an important tool for territorial planning requirements of public administrations and engineering geologists (e.g. in hydrogeological and seismic risk evaluation). Field geologists performed data input in the geological data base by alternating field campaigns and data input throughout the year, taking advantage of periods when field activities are slackened (i.e. according to climate conditions). In this way, data entry is nearly synchronous with data collection, and field data become quickly accessible. Data entry by the field geologists on one side slows down the field activity, however, it guarantees a precise digitalization of geometric data and a correct attribute assignment, allowing to optimize working time. To allow the data entry to non-GIS-specialized users, we developed an ArcView®-VisualBasic®-MSAccess® application, enabling the simultaneous acquisition of geometric and alphanumeric data. Data base management and cartographic production are performed with ArcInfo®, through specific procedures which, after data reorganization and control (both alphanumeric and geometric), lead to the final cartographic output at different scales. The 1:10.000 geological database is migrated in the ArcSDE structure and prepared for data view, query and download (www.cartografia.regione.lombardia.it/cargweb) using ESRI (ArcIMS) tools. From the 1:10.000 geological database we derived the database for the 1:50.000 CARG maps by both automatic and manual generalization according to the CARG-APAT standards. During the different phases of the project, several problems arose, due to both project organization and data storage system (from data collection in the field to elaboration and digitalization, and, in case, to final publication). – Data collection: the survey activity was divided between «bedrock » and «quaternary» specialists. The double survey provided a high-quality geological description of the territory, but slowed the generation of the data-flow. Based on this experience, the last assigned areas are surveyed by a single geologist, under the supervision of quaternary and bedrock experts. – Users feedback: geologists are normally used to draw their maps on paper; learning how to produce electronic maps can be difficult, and the software tools have to be studied very carefully and present user friendly interfaces. Nevertheless, in our experience, a training period has to be planned, and geologists have to be supported by a GIS expert, who can understand their needs and modify the software accordingly. – System architecture: the ArcView®-VisualBasic®-MSAccess® (Windows platform) – ArcInfo® (UNIX platform) environment, revealed problems in the client-server stability of an earlier version; some unsolved troubles remain, mainly related to the network architecture. The presence in the CARG-Regione Lombardia crew of consultant geologists, experienced and trained in collection, analysis and data entry in the final database, accelerated the critical phases of: – Data base derivation from Regione Lombardia dataset to CARG-APAT standard

Characterization of active fault scarps from LiDAR data: a case 1 study from Central 2 Apennines (Italy)

A high resolution DEM (1 ms spacing) derived from an airborne LiDAR campaign was 11 used in an attempt to characterize the structural and erosive elements of the geometry of the Pettino 12 fault, a seismogenic normal fault in Central Apennines (Italy). Four 90- to 280 m -long fault scarp 13 segments were selected and the surface between the base and the top of the scarps was analyzed 14 through the statistical analysis of the following DEM-derived parameters: altitude, height of the 15 fault scarp, distance along strike, slope and aspect. The results identify slopes of up to 40° in faults 16 lower reaches interpreted as fresh faces, 34° up the faces. The Pettino fault maximum long slipe17 rate (0.6-1.1 mm/yr) was estimated from the scarp heights, which are up to 12 and 19 m in the 18 selected four segments, and the age (ca. 18 ka) of the last glacial erosional phase in the area. The 19 combined analysis of the DEM-derived parameters allow us to (a) define aspects of 3D scarp 20 geometry, (b) decipher its geomorphological significance, and (c) estimate the long-term slip rate

The Folding Mechanism of the SH3 Domain from Grb2

SH3 domains are small protein modules involved in the regulation of important cellular pathways. These domains mediate protein-protein interactions recognizing motifs rich in proline on the target protein. The SH3 domain from Grb2 (Grb2-SH3) presents the typical structure of an SH3 domain composed of two-three stranded antiparallel \u3b2-sheets orthogonally packed onto each other, to form a single hydrophobic core. Grb2 interacts, via SH3 domain, with Gab2, a scaffolding disordered protein, triggering some key metabolic pathways involved in cell death and differentiation. In this work we report a mutational analysis (\u3c6-value analysis) of the folding pathway of Grb2-SH3 that, coupled with molecular dynamic simulations, allows us to assess the structure of the transition state and the mechanism of folding of this domain. Data suggest that Grb2-SH3 folds via a native-like, diffused transition state with a concurrent formation of native-like secondary and tertiary structure (nucleation-condensation mechanism) and without the accumulation of folding intermediates. The comparison between our data and previous folding studies on SH3 domains belonging to other proteins, highlights that proteins of this class may fold via alternative pathways, stabilized by different nuclei leading or not to accumulation of folding intermediates. This comparative analysis suggests that the alternative folding pathways for this class of SH3 domains can be selectively regulated by the specific aminoacid sequences

HISTORICAL AND ARCHAEOSEISMIC STUDIES IN THE POLLINO AREA

Section 1. Reappraisal of the January 8, 1693 Pollino earthquake Section 2. Archaeoseismic field survey Section 3. Investigation of damaged speleothem