The H-factor as a novel quality metric for homology modeling

BACKGROUND: Drug discovery typically starts with the identification of a potential target that is then tested and validated either through high-throughput screening against a library of drug compounds or by rational drug design. When the putative target is a protein, the latter approach requires the knowledge of its structure. Finding the structure of a protein is however a difficult task. Significant progress has come from high-resolution techniques such as X-ray crystallography and NMR; there are many proteins however whose structure have not yet been solved. Computational techniques for structure prediction are viable alternatives to experimental techniques for these cases. However, the proper validation of the structural models they generate remains an issue. FINDINGS: In this report, we focus on homology modeling techniques and introduce the H-factor, a new indicator for assessing the quality of protein structure models generated with these techniques. The H-factor is meant to mimic the R-factor used in X-ray crystallography. The method for computing the H-factor is fully described with a demonstration of its effectiveness on a test set of target proteins. CONCLUSIONS: We have developed a web service for computing the H-factor for models of a protein structure. This service is freely accessible at http://koehllab.genomecenter.ucdavis.edu/toolkit/h-factor

Crustal and upper-mantle structure in the Eastern Mediterranean from the analysis of surface wave dispersion curves

The dispersive properties of surface waves are used to infer earth structure in the Eastern Mediterranean region. Using group velocity maps for Rayleigh and Love waves from 7100 s, we invert for the best 1D crust and uppermantle structure at a regular series of points. Assembling the results produces a 3D lithospheric model, along with corresponding maps of sediment and crustal thickness. A comparison of our results to other studies finds the uncertainties of the Moho estimates to be about 5 km. We find thick sediments beneath most of the Eastern Mediterranean basin, in the Hellenic subduction zone and the Cyprus arc. The Ionian Sea is more characteristic of oceanic crust than the rest of the Eastern Mediterranean region as demonstrated in particular by the crustal thickness. We also find significant crustal thinning in the Aegean Sea portion of the backarc, particularly towards the south. Notably slower Swave velocities are found in the uppermantle, especially in the northern Red Sea and Dead Sea Rift, central Turkey, and along the subduction zone. The low velocities in the uppermantle that span from North Africa to Crete, in the Libyan Sea, might be an indication of serpentinized mantle from the subducting African lithosphere. We also find evidence of a strong reverse correlation between sediment and crustal thickness which, while previously demonstrated for extensional regions, also seems applicable for this convergence zone

Rayleigh wave dispersion measurements reveal low-velocity zones beneath the new crust in the Gulf of California

Rayleigh wave tomography provides images of the shallow mantle shear wave velocity structure beneath the Gulf of California. Low-velocity zones (LVZs) are found on axis between 26 and 50 km depth beneath the Guaymas Basin but mostly off axis under the other rift basins, with the largest feature underlying the Ballenas Transform Fault. We interpret the broadly distributed LVZs as regions of partial melting in a solid mantle matrix. The pathway for melt migration and focusing is more complex than an axis-centered source aligned above a deeper region of mantle melt and likely reflects the magmatic evolution of rift segments. We also consider the existence of solid lower continental crust in the Gulf north of the Guaymas Basin, where the association of the LVZs with asthenospheric upwelling suggests lateral flow assisted by a heat source. These results provide key constraints for numerical models of mantle upwelling and melt focusing in this young oblique rift

Elementary seismological analysis applied to the April 6, 2009 L'Aquila mainshock and its larger aftershock

To understand the source complexity of the April 6, 2009 L’Aquila earthquake (MW = 6.3), a quick seismological analysis is done on the waveforms of the mainshock and the larger aftershock that occurred on April 7, 2009. We prove that a simple waveform analysis gives useful insights into the source complexity, as soon as the seismograms are available after the earthquake occurrence, whereas the reconstruction of the rupture dynamics through the application of sophisticated techniques requires a definitely longer time. We analyzed the seismograms recorded at broadband and strong motion stations and provided firm constraints on rupture kinematics, slip distribution, and static surface deformation, also discriminating the actual fault plane. We found that two distinct rupture patches associated with different fracture propagation directions and possibly occurring on distinct rupture planes, characterized the source kinematics of the April 6 events. An initial updip propagation successively proceeds toward SE, possibly on a different plane. We also show that the same processing, applied to the April 7, 2009 aftershock (MW = 5.6), allows us to obtain useful information also in the case of lower magnitude events. Smaller events with similar location and source mechanism as the mainshock, to be used as Green’s empirical function, occur in the days before or within tens of minutes to a few hours after the mainshock. These quick, preliminary analyses can provide useful constraints for more refined studies, such as inversion of data for imaging the rupture evolution and the slip distribution on the fault plane. We suggest implementing these analyses for real, automatic or semi-automatic, investigations

Seismic structure beneath the Gulf of California: a contribution from group velocity measurements

Rayleigh wave group velocity dispersion measurements from local and regional earthquakes are used to interpret the lithospheric structure in the Gulf of California region. We compute group velocity maps for Rayleigh waves from 10 to 150 s using earthquakes recorded by broad-band stations of the Network of Autonomously Recording Seismographs in Baja California and Mexico mainland, UNM in Mexico, BOR, DPP and GOR in southern California and TUC in Arizona. The study area is gridded in 120 longitude cells by 180 latitude cells, with an equal spacing of 10 × 10 km. Assuming that each gridpoint is laterally homogeneous, for each period the tomographic maps are inverted to produce a 3-D lithospheric shear wave velocity model for the region. Near the Gulf of California rift axis, we found three prominent low shear wave velocity regions, which are associated with mantle upwelling near the Cerro Prieto volcanic field, the Ballenas Transform Fault and the East Pacific Rise. Upwelling of the mantle at lithospheric and asthenospheric depths characterizes most of the Gulf. This more detailed finding is new when compared to previous surface wave studies in the region. A low-velocity zone in northcentral Baja at ∼28ºN which extends east–south–eastwards is interpreted as an asthenospheric window. In addition, we also identify a well-defined high-velocity zone in the upper mantle beneath central-western Baja California, which correlates with the previously interpreted location of the stalled Guadalupe and Magdalena microplates. We interpret locations of the fossil slab and slab window in light of the distribution of unique post-subduction volcanic rocks in the Gulf of California and Baja California. We also observe a high-velocity anomaly at 50-km depth extending down to ∼130 km near the southwestern Baja coastline and beneath Baja, which may represent another remnant of the Farallon slab

Coastal sensitivity/vulnerability characterization and adaptation strategies: A review

Coastal area constitutes a vulnerable environment and requires special attention to preserve ecosystems and human activities therein. To this aim, many studies have been devoted both in past and recent years to analyzing the main factors affecting coastal vulnerability and susceptibility. Among the most used approaches, the Coastal Vulnerability Index (CVI) accounts for all relevant variables that characterize the coastal environment dealing with: (i) forcing actions (waves, tidal range, sea-level rise, etc.), (ii) morphological characteristics (geomorphology, foreshore slope, dune features, etc.), (iii) socio-economic, ecological and cultural aspects (tourism activities, natural habitats, etc.). Each variable is evaluated at each portion of the investigated coast, and associated with a vulnerability level which usually ranges from 1 (very low vulnerability), to 5 (very high vulnerability). Following a susceptibility/vulnerability analysis of a coastal stretch, specific strategies must be chosen and implemented to favor coastal resilience and adaptation, spanning from hard solutions (e.g., groins, breakwaters, etc.) to soft solutions (e.g., beach and dune nourishment projects), to the relocation option and the establishment of accommodation strategies (e.g., emergency preparedness)

Implementação da metodologia BIM em um gabinete de estruturas

Building Information Modeling (BIM) é uma inovadora metodologia de trabalho colaborativo que vem proporcionar uma nova abordagem à gestão da informação na construção, baseada na elaboração de um modelo digital da informação. A metodologia BIM assenta na geração de um modelo digital centralizado de toda a informação relacionada com a construção, acessível a todos os intervenientes, permitindo reduzir significativamente a ocorrência de erros e conflitos e, por consequência, dos custos associadas às diferentes fases do ciclo de vida de uma obra. A utilização de modelos computacionais para análise e dimensionamento de estruturas é já uma prática corrente entre os projetistas estruturais. Nesta dissertação é realizado um estudo sobre o estado do conhecimento relativo a metodologia BIM, com foco no processo corrente no desenvolvimento do projeto de estruturas. Assim é realizado o estudo utilizando plataformas e ferramentas BIM comuns a um gabinete de projeto de estruturas na elaboração do projeto de um edifício. São analisadas as capacidades destas ferramentas procurando estabelecer recomendações para a modelação e gestão do fluxo de informação, na perspectiva do engenheiro de estruturas. É verificado o nível de interoperabilidade entre os programas, por ligação direta e a partir de ficheiros em formato aberto, tendo atenção a análise da qualidade de informação transferida e na consistência do produto final. Durante o processo são identificadas limitações e são referidas as adaptações pertinentes a serem realizadas, de forma a otimizar a aplicação da metodologia BIM no projeto de estruturas.Building Information Modeling (BIM) is an innovative methodology for collaborative work that has to provide a new approach to information management in construction, based on the elaboration of a virtual information model. The methodology allows the creation of a digital model in which all information linked with the construction is accessible for all stakeholders. Existence of this open digital model significantly improves the detection and solution for errors or conflicts and therefore, reduces costs associated with different stages of the life cycle from the building. The use of computer models for analysis and design of structures is already current practice among structural designers. In this thesis is studied the use of BIM methodology with focus on the common design process of structures. BIM platforms and tools are used in the design of a building structures and the capabilities of these tools are analyzed, applied to the design and an optimized work-flow is presented from the viewpoint of the structural engineer. The level of interoperability between the programs is checked by direct link and from open files, paying attention to the analysis of the quality of information transferred and the consistency of the final product. During the process, limitations are identified and the adjustments are referred in order to optimize the application of BIM methodology in the design of structures

Normal faults and thrusts re-activated by deep fluids: the 6 April 2009 Mw 6.3 L’Aquila earthquake, central Italy.

On April 6 2009, a Mw=6.3 earthquake occurred in the central Apennines (Italy) damaging L’Aquila city and the surrounding country. We relocate the October 2008-April 6 2009 foreshocks and about 2000 aftershocks occurred between April 6 and April 30 2009, by applying a double-difference technique and determine the stress field from focal mechanisms. The events concentrate in the upper 15 km of the crust. Three main NW-SE to NNW-SSE striking, 30°-45° and 80°-90° dipping faults activate during the seismic sequence. Among these, a normal fault and a thrust were re-activated with dip-slip movements in response to NE-SW extension. The structural maturity of the seismogenic fault system is lower than that displayed by other systems in southern Apennines, because of the lower strain rate of the central sector of the chain with respect to the southern one. VP/VS increases progressively from October 2008 to the April 6 2009 mainshock occurrence along a NW-SE strike due to an increment in pore fluid pressure along the fault planes. Pore pressure diffusion controls the space-time evolution of aftershocks. A hydraulic diffusivity of 80 m2/s and a seismogenic permeability of about 10-12 m2 suggest the involvement of gas-rich (CO2) fluids within a highly fractured medium. Suprahydrostatic, high fluid pressure (about 200 MPa at 10 km of depth) within overpressurized traps, bounded by pre-existing structural and/or lithological discontinuities at the lower-upper crust boundary, are required to activate the April 2009 sequence. Traps are the storage zone of CO2-rich fluids uprising from the underlying, about 20 km deep, metasomatized mantle wedge. These traps easily occur in extensional regimes like in the axial sector of Apennines, but are difficult to form in strike-slip regimes, where sub-vertical faults may cross the entire crust. In the Apennines, fluids may activate faults responsible for earthquakes up to Mw=5-6. Deep fluids more than tectonic stress may control the seismotectogenesis of accretionary wedges

Coastal Sensitivity/Vulnerability Characterization and Adaptation Strategies: A Review

Coastal area constitutes a vulnerable environment and requires special attention to preserve ecosystems and human activities therein. To this aim, many studies have been devoted both in past and recent years to analyzing the main factors affecting coastal vulnerability and susceptibility. Among the most used approaches, the Coastal Vulnerability Index (CVI) accounts for all relevant variables that characterize the coastal environment dealing with: (i) forcing actions (waves, tidal range, sea-level rise, etc.), (ii) morphological characteristics (geomorphology, foreshore slope, dune features, etc.), (iii) socio-economic, ecological and cultural aspects (tourism activities, natural habitats, etc.). Each variable is evaluated at each portion of the investigated coast, and associated with a vulnerability level which usually ranges from 1 (very low vulnerability), to 5 (very high vulnerability). Following a susceptibility/vulnerability analysis of a coastal stretch, specific strategies must be chosen and implemented to favor coastal resilience and adaptation, spanning from hard solutions (e.g., groins, breakwaters, etc.) to soft solutions (e.g., beach and dune nourishment projects), to the relocation option and the establishment of accommodation strategies (e.g., emergency preparedness)