Probing prothrombin structure by limited proteolysis

Prothrombin, or coagulation factor II, is a multidomain zymogen precursor of thrombin that undergoes an allosteric equilibrium between two alternative conformations, open and closed, that react differently with the physiological activator prothrombinase. Specifically, the dominant closed form promotes cleavage at R320 and initiates activation along the meizothrombin pathway, whilst the open form promotes cleavage at R271 and initiates activation along the alternative prethrombin-2 pathway. Here we report how key structural features of prothrombin can be monitored by limited proteolysis with chymotrypsin that attacks W468 in the flexible autolysis loop of the protease domain in the open but not the closed form. Perturbation of prothrombin by selective removal of its constituent Gla domain, kringles and linkers reveals their long-range communication and supports a scenario where stabilization of the open form switches the pathway of activation from meizothrombin to prethrombin-2. We also identify R296 in the A chain of the protease domain as a critical link between the allosteric open-closed equilibrium and exposure of the sites of cleavage at R271 and R320. These findings reveal important new details on the molecular basis of prothrombin functio

THE SANSEVERO CHAPEL, A THREE-DIMENSIONAL POINT OF VIEW

Abstract. In this article, the importance of the three-dimensional survey in architectural spaces will be studied, taking special relevance in the study of the perception of perspective, since three-dimensional space would not be understood from a two-dimensional representation of space. The project aims to develop a comparison between the representation systems based on the automatic acquisition of various data by different 3D survey techniques. In particular, the document reports the results of an analysis based on the Sansevero Chapel in Naples.</p

URBAN DESIGN STRATEGIES FOR THE UPCYCLING OF URBAN INFRASTRUCTURE RESIDUAL POCKETS: 3D CITY MODELLING FROM OPEN DATA AND LOW-COST RAPID MAPPING TOOLS

This paper deals with the 3D City Modelling specific procedure developed as a tool to support strategies for urban regeneration, within the framework of the B-ROAD research project.The B-ROAD research project, whose acronym stands for Below the Road, is developing urban design strategies for upcycling urban infrastructure residual pockets.The B-ROAD’s methodology is conceived as research by design as it is carried out by creating pilot scenarios, disclosing the latent and still unexpressed potential of these wasted areas and displaying their potential transformations, to turn them into precious resources for the contemporary city.The 3D City Modelling of the study area has proved to be essential and strategic yet often complex and critical as most of the spatial and architectural features of B-ROAD spaces, as well as their potential, cannot be detected nor represented through the traditional means of representation of urbanised land, as aerial survey-based representations, or GIS. Likewise, traditional, or even cutting-edge, survey techniques that can be used to acquire missing data are often costly and time-consuming, thus making it hardly impossible to achieve the purpose of extensive and deep knowledge of such a vast area. Thus, 3D City Modelling aimed at examining spaces and providing a final representation of pilot scenarios has been a crucial stage requiring a specific in-depth study.</p

Inclined Surface Locomotion Strategies for Spherical Tensegrity Robots

This paper presents a new teleoperated spherical tensegrity robot capable of performing locomotion on steep inclined surfaces. With a novel control scheme centered around the simultaneous actuation of multiple cables, the robot demonstrates robust climbing on inclined surfaces in hardware experiments and speeds significantly faster than previous spherical tensegrity models. This robot is an improvement over other iterations in the TT-series and the first tensegrity to achieve reliable locomotion on inclined surfaces of up to 24\degree. We analyze locomotion in simulation and hardware under single and multi-cable actuation, and introduce two novel multi-cable actuation policies, suited for steep incline climbing and speed, respectively. We propose compelling justifications for the increased dynamic ability of the robot and motivate development of optimization algorithms able to take advantage of the robot's increased control authority.Comment: 6 pages, 11 figures, IROS 201

Molecular and Biological Analysis on Ommastrephes caroli Findings in the Central Western Mediterranean Sea (Sardinian Waters) Including First Age Investigation Using Eye Lenses and Beaks

Molecular identifications based on two mitochondrial markers (cytochrome c oxidase subunit I -COI- and 16S ribosomal RNA gene -16S-) have been implemented to confirm the morphological identification of eight specimens collected in the Central western Mediterranean. Molecular data show they belonged to a recently resurrected species of the genus Ommastrephes, i.e., O. caroli, known to be distributed in the Atlantic Ocean and Mediterranean Sea. Despite this, molecular analyses of COI sequences evidenced the presence of potential genetic differentiation between Mediterranean and Atlantic samples, highlighting the need for further studies, with more individuals to investigate the connectivity between individuals living in the two areas. Furthermore, morphological, biometric and reproductive features here reported, could be useful in evaluating possible distinctive biological features between the Mediterranean and Atlantic individuals. Female mature size was larger than the male. The relationships obtained between the beak measurements and body sizes (DML; TW) were better described by a power model. Asynchronous oocytes development with relatively small oocytes (0.05–1.10 mm) and a protracted intermittent spawning with active feeding were observed. This study also reported for the specie O. caroli the first data on the potential fecundity estimated (840061 oocytes), the oviducal load (90000 ripe oocytes) as well as the number of seminal receptacles and the size and morphology of the spermatangia found in the buccal mass of all mated females. Even if on a low sample size, beaks and eye lenses were used for the first time in O. caroli for age estimation. The statistically significant relationship found between increments counted in eye lenses and beaks highlighted the reliability of the lenses to estimate age in O. caroli, even if further studies will be needed for its validation. Assuming a daily increment for both structures, a mean life span of about 12–13 months was estimated for both sexes, which is consistent with the sexual maturity condition observed in all the samples and the semelparity known for cephalopods coleoids

The Importance and Potential Value of a Regional Midsize Arthropod Collection: An Example of IBULC

During the last three centuries, people involved in natural history sciences have produced thousands of natural history collections worldwide. Specimens have been used for scientific proof of various discoveries and for gaining new knowledge in many disciplines of science not only in the area of biodiversity but also in taxonomy, species biology and ecology, parasitology, evolution, organisms’ responses to climate change, nature conservation and many other biological sub-disciplines. Despite never-ending financial struggles, the world’s largest collections as well as many regional midsize collections contain billions of specimens. This provides an enormous database for present and future studies. This article presents a critical description of the material of the Institute of Biology, University of Latvia collection (IBULC) containing roughly 59,000 identified arthropod individuals of about 3,700 species, including twenty-eight primary types as a part of around ninety type specimens, to illustrate the importance of midsize regional natural history collections in detail.Some Rights Reserved. Public Licensed Material: Available under the terms and conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Public License (CC BY-NC-ND 4.0). The use of this material is permitted for non-commercial use provided the creator(s) and publisher receive attribution. No derivatives of this version are permitted. Official terms of this public license apply as indicated here: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcod

Holistic Slowdown Driven Scheduling and Resource Management for Malleable Jobs

In job scheduling, the concept of malleability has been explored since many years ago. Research shows that malleability improves system performance, but its utilization in HPC never became widespread. The causes are the difficulty in developing malleable applications, and the lack of support and integration of the different layers of the HPC software stack. However, in the last years, malleability in job scheduling is becoming more critical because of the increasing complexity of hardware and workloads. In this context, using nodes in an exclusive mode is not always the most efficient solution as in traditional HPC jobs, where applications were highly tuned for static allocations, but offering zero flexibility to dynamic executions. This paper proposes a new holistic, dynamic job scheduling policy, Slowdown Driven (SD-Policy), which exploits the malleability of applications as the key technology to reduce the average slowdown and response time of jobs. SD-Policy is based on backfill and node sharing. It applies malleability to running jobs to make room for jobs that will run with a reduced set of resources, only when the estimated slowdown improves over the static approach. We implemented SD-Policy in SLURM and evaluated it in a real production environment, and with a simulator using workloads of up to 198K jobs. Results show better resource utilization with the reduction of makespan, response time, slowdown, and energy consumption, up to respectively 7%, 50%, 70%, and 6%, for the evaluated workloads

Characterization of resting state activity in MCI individuals

Objectives. Aging is the major risk factor for Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI). The aim of this study was to identify novel modifications of brain functional connectivity in MCI patients. MCI individuals were compared to healthy elderly subjects. Methods. We enrolled 37 subjects (age range 60–80 y.o.). Of these, 13 subjects were affected by MCI and 24 were age-matched healthy elderly control (HC). Subjects were evaluated with Mini Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and prose memory (Babcock story) tests. In addition, with functional Magnetic Resonance Imaging (fMRI), we investigated resting state network (RSN) activities. Resting state (Rs) fMRI data were analyzed by means of Independent Component Analysis (ICA). Subjects were followed-up with neuropsychological evaluations for three years. Results. Rs-fMRI of MCI subjects showed increased intrinsic connectivity in the Default Mode Network (DMN) and in the Somatomotor Network (SMN). Analysis of the DMN showed statistically significant increased activation in the posterior cingulate cortex (PCC) and left inferior parietal lobule (lIPL). During the three years follow-up, 4 MCI subjects converted to AD. The subset of MCI AD-converted patients showed increased connectivity in the right Inferior Parietal Lobule (rIPL). As for SMN activity, MCI and MCI-AD converted groups showed increased level of connectivity in correspondence of the right Supramarginal Gyrus (rSG). Conclusions. Our findings indicate alterations of DMN and SMN activity in MCI subjects, thereby providing potential imaging-based markers that can be helpful for the early diagnosis and monitoring of these patients

Random, blocky and alternating ordering in supramolecular polymers of chemically bidisperse monomers

As a first step to understanding the role of molecular or chemical polydispersity in self-assembly, we put forward a coarse-grained model that describes the spontaneous formation of quasi-linear polymers in solutions containing two self-assembling species. Our theoretical framework is based on a two-component self-assembled Ising model in which the bidispersity is parameterized in terms of the strengths of the binding free energies that depend on the monomer species involved in the pairing interaction. Depending upon the relative values of the binding free energies involved, different morphologies of assemblies that include both components are formed, exhibiting paramagnetic-, ferromagnetic- or anti ferromagnetic-like order,i.e., random, blocky or alternating ordering of the two components in the assemblies. Analyzing the model for the case of ferromagnetic ordering, which is of most practical interest, we find that the transition from conditions of minimal assembly to those characterized by strong polymerization can be described by a critical concentration that depends on the concentration ratio of the two species. Interestingly, the distribution of monomers in the assemblies is different from that in the original distribution, i.e., the ratio of the concentrations of the two components put into the system. The monomers with a smaller binding free energy are more abundant in short assemblies and monomers with a larger binding affinity are more abundant in longer assemblies. Under certain conditions the two components congregate into separate supramolecular polymeric species and in that sense phase separate. We find strong deviations from the expected growth law for supramolecular polymers even for modest amounts of a second component, provided it is chemically sufficiently distinct from the main one.Comment: Submitted to Macromolecules, 6 figures. arXiv admin note: substantial text overlap with arXiv:1111.176