Repacking protein cores with backbone freedom: structure prediction for coiled coils.

Progress in homology modeling and protein design has generated considerable interest in methods for predicting side-chain packing in the hydrophobic cores of proteins. Present techniques are not practically useful, however, because they are unable to model protein main-chain flexibility. Parameterization of backbone motions may represent a general and efficient method to incorporate backbone relaxation into such fixed main-chain models. To test this notion, we introduce a method for treating explicitly the backbone motions of alpha-helical bundles based on an algebraic parameterization proposed by Francis Crick in 1953 [Crick, F. H. C. (1953) Acta Crystallogr. 6, 685-689]. Given only the core amino acid sequence, a simple calculation can rapidly reproduce the crystallographic main-chain and core side-chain structures of three coiled coils (one dimer, one trimer, and one tetramer) to within 0.6-A root-mean-square deviations. The speed of the predictive method [approximately 3 min per rotamer choice on a Silicon Graphics (Mountain View, CA) 4D/35 computer] permits it to be used as a design tool.

Common origin for surface reconstruction and the formation of chains of metal atoms

During the fracture of nanocontacts gold spontaneously forms freely suspended chains of atoms, which is not observed for the isoelectronic noble metals Ag and Cu. Au also differs from Ag and Cu in forming reconstructions at its low-index surfaces. Using mechanically controllable break junctions we show that all the 5d metals that show similar reconstructions (Ir, Pt, and Au) also form chains of atoms, while both properties are absent in the 4d neighbor elements (Rh, Pd, and Ag), indicating a common origin for these two phenomena. A competition between s and d bonding is proposed as an explanation.

Morocco, 1908 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Maroc, carte dessinée par R. de Flotte de Roquevaire. It was published by Maison Andriveau-Goujon, Henry Barrère Editeur in 1908. Scale 1:1,000,000. Covers Morocco and portions of Algeria. Map in French. The image inside the map neatline is georeferenced to the surface of the earth and fit to a modified 'Europe Lambert Conformal Conic' projection with a central meridian of 7 degrees West. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as drainage, cities and other human settlements, roads, ruins, territorial boundaries, shoreline features, and more. Relief shown by landforms and spot heights. Includes indexs and insets: Mazagan (Scale 1:20,000) -- Casa Blanca (Scale 1:20,000) -- Tanger (Scale 1:20,000) -- Safi (Scale 1:20,000) -- Larache (Scale 1:20,000) -- El-Qsar el-Kebir (Scale 1:20,000) -- Rabat (Scale 1:50,000) -- Taroudant (Scale 1:40,000) -- Mogador (Scale 1:20,000) -- Agadir Irir (Scale 1:20,000) -- Oujda (Scale 1:20,000) -- El-Aïoun Si Mellouk (Scale 1:10,000) -- Meknes (Scale 1:50,000) -- Fes (Scale 1:30,000) -- Figuig (Scale 1:200,000) -- Marrakech (Scale 1:60,000) -- Environs de Fes (Scale 1:100,000). This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection as part of the Open Collections Program at Harvard University project: Islamic Heritage Project. Maps selected for the project represent a range of regions, originators, ground condition dates, scales, and purposes. The Islamic Heritage Project consists of over 100,000 digitized pages from Harvard's collections of Islamic manuscripts and published materials. Supported by Prince Alwaleed Bin Talal and developed in association with the Prince Alwaleed Bin Talal Islamic Studies Program at Harvard University.

Maroc

carte dessinée par R. de Flotte de Roquevaire.

Investigating the Role of cAMP-Signaling in the Regulation of Vascular Endothelial Cell Adaptive Responses to Fluid Shear Stress

The circulating blood exerts a force on the vascular endothelium, termed fluid shear stress (FSS), which directly impacts numerous vascular endothelial cell (VEC) functions. For example, high rates of linear and undisturbed (i.e. laminar) blood flow maintains a protective and quiescent VEC phenotype. Meanwhile, deviations in blood flow, which can occur at vascular branchpoints and large curvatures, create areas of low, and/or oscillatory FSS, and promote a pro-inflammatory, pro-thrombotic and hyperpermeable phenotype. Indeed, it is known that these areas are prone to the development of atherosclerotic lesions. Herein, we show that cyclic nucleotide phosphodiesterase (PDE) 4D (PDE4D) activity is increased by FSS in human arterial endothelial cells (HAECs) and that this activation regulates the activity of cAMP-effector protein, Exchange Protein-activated by cAMP-1 (EPAC1), in these cells. Importantly, we also show that these events directly and critically impact HAEC responses to FSS, especially when FSS levels are low. Both morphological events induced by FSS, as measured by changes in cell alignment and elongation in the direction of FSS, and the expression of critical FSS-regulated genes, including Krüppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS) and thrombomodlin (TM), are mediated by EPAC1/PDE4D signaling. At a mechanistic level, we show that EPAC1/PDE4D acts through the vascular endothelial-cadherin (VECAD)/ platelet-cell adhesion molecule-1 (PECAM1)/vascular endothelial growth factor receptor 2 (VEGFR2) mechanosensor to activate downstream signaling though Akt. Given the critical role of PDE4D in mediating these effects, we also investigated the impact of various patterns of FSS on the expression of individual PDE genes in HAECs. Notably, PDE2A was significantly upregulated in response to high, laminar FSS, while PDE3A was upregulated under low, oscillatory FSS conditions only. These data may provide novel therapeutic targets to limit FSS-dependent endothelial cell dysfunction (ECD) and atherosclerotic development.

Inference of binding affinity from neuronal receptors in humans

Tese de mestrado, Bioinformática e Biologia Computacional (Bioinformática), Universidade de Lisboa, Faculdade de Ciências, 2016

La digitalizzazione del processo costruttivo: la strategia Building Information Modeling and Management (BIMM) applicata ad un caso di studio di edilizia scolastica.

L’obiettivo della tesi è quello di fare una panoramica sulla strategia BIM e quindi sulla digitalizzazione del processo costruttivo. Grazie alla analisi di un caso di studio, altro obiettivo è quello di analizzare e valutare la metodologia BIM 4D/5D, ossia la gestione dei tempi e dei costi di realizzazione dell’opera. Nella prima fase si affronta il tema del BIM, con una analisi sull’evoluzione degli strumenti di elaborazione e rappresentazione digitale del progetto architettonico, su come questi strumenti si differenzino sia dal punto di vista operativo che concettuale rivoluzionando il flusso di lavoro odierno. Quindi, partendo da un’analisi che e ritrae l’estrema frammentazione del settore delle costruzioni, si va ad analizzare come il BIM aumenti e favorisca la collaborazione delle parti interessate, armonizzando l’intero processo costruttivo dell’opera. Si prosegue con l'esame della diffusione e del livello di maturità degli strumenti BIM, di come i privati e le amministrazioni pubbliche, a livello mondiale, stiano spingendo per favorire l’adozione della metodologia BIM. Inoltre si analizzano le dinamiche dell’interoperabilità, delle metodologie e protocolli di interscambio dati, che sono un elemento chiave per il successo del BIM per via dei numerosi strumenti, specializzati nelle varie discipline del settore edile. Nella terza parte, dedicata al Project Management di un caso di studio, si verifica la bontà delle metodologie teorizzate attraverso la realizzazione di un modello virtuale in Revit. Dal modello realizzato dal laureando sono estrapolate le informazioni necessarie alla gestione, e tramite il software STRVison CPM, si elaborano i principali documenti per la progettazione e gestione del cantiere: il CM, il CME, i tempi operativi, il cronoprogramma Gantt. Obbiettivo è constatare l’effettivo livello di maturità della strategia BIM 4D e 5D e la reale possibilità di un impiego capillare nel panorama italiano del settore delle costruzioni.

Analysis of analogue models by helical X-ray computed tomography

The aim of analogue model experiments in geology is to simulate structures in nature under specific imposed boundary conditions using materials whose rheological properties are similar to those of rocks in nature. In the late 1980s, X-ray computed tomography (CT) was first applied to the analysis of such models. In early studies only a limited number of cross-sectional slices could be recorded because of the time involved in CT data acquisition, the long cooling periods for the X-ray source and computational capacity. Technological improvements presently allow an almost unlimited number of closely spaced serial cross-sections to be acquired and calculated. Computer visualization software allows a full 3D analysis of every recorded stage. Such analyses are especially valuable when trying to understand complex geological structures, commonly with lateral changes in 3D geometry. Periodic acquisition of volumetric data sets in the course of the experiment makes it possible to carry out a 4D analysis of the model, i.e. 3D analysis through time. Examples are shown of 4D analysis of analogue models that tested the influence of lateral rheological changes on the structures obtained in contractional and extensional settings.

On ANOVA Decompositions of Kernels and Gaussian Random Field Paths

The FANOVA (or “Sobol’-Hoeffding”) decomposition of multivariate functions has been used for high-dimensional model representation and global sensitivity analysis. When the objective function f has no simple analytic form and is costly to evaluate, computing FANOVA terms may be unaffordable due to numerical integration costs. Several approximate approaches relying on Gaussian random field (GRF) models have been proposed to alleviate these costs, where f is substituted by a (kriging) predictor or by conditional simulations. Here we focus on FANOVA decompositions of GRF sample paths, and we notably introduce an associated kernel decomposition into 4 d 4d terms called KANOVA. An interpretation in terms of tensor product projections is obtained, and it is shown that projected kernels control both the sparsity of GRF sample paths and the dependence structure between FANOVA effects. Applications on simulated data show the relevance of the approach for designing new classes of covariance kernels dedicated to high-dimensional kriging.

(Table 2) Picked maximum velocities from 3 radars (RAY, SHK, and SUM), showing 10 explosions at Erebus volcano, Antarctica, and their respective directivity vectors

We used a novel system of three continuous wave Doppler radars to successfully record the directivity of i) Strombolian explosions from the active lava lake of Erebus volcano, Antarctica, ii) eruptions at Stromboli volcano, Italy, and iii) a man-made explosion in a quarry. Erebus volcano contains a convecting phonolite lava lake, presumably connected to a magma chamber at depth. It is one of the few open vent volcanoes that allow a direct observation of source processes during explosions. Its lava lake is the source of frequent violent Strombolian explosions, caused by large gas bubbles bursting at the lake surface. The exact mechanism of these bubble bursts is unclear, as is the mechanism of the creation of the infrasound signal accompanying the explosions. We use the Doppler radar data to calculate the directivity of Strombolian eruptions at Erebus. This allows us to derive information about the expected type of infrasound source pattern (i.e. the role of a dipole in addition to the monopole signature) and the physical structure of the volcano. We recorded 10 large explosions simultaneously with three radars, enabling us to calculate time series of 3D directivity vectors (i.e. effectively 4D), which describe the direction of preferred expansion of the gas bubble during an explosion. Such directivity information allows a comparison to dipole infrasound radiation patterns recorded during similar explosions only a few weeks later. Video observations of explosions support our interpretation of the measurements. We conclude that at Erebus, the directivity of explosions is mainly controlled by random processes. Since the geometry of the uppermost conduit is assumed to have a large effect on the directivity of explosions, the results suggest a largely symmetrical uppermost conduit with a vertical axis of symmetry. For infrasound recordings, a significant dipole signature can be expected in addition to the predominant monopole signature.