Thermodynamics of beta-amyloid fibril formation

Amyloid fibers are aggregates of proteins. They are built out of a peptide called $\beta$--amyloid (A$\beta$) containing between 41 and 43 residues, produced by the action of an enzyme which cleaves a much larger protein known as the Amyloid Precursor Protein (APP). X-ray diffraction experiments have shown that these fibrils are rich in $\beta$--structures, whereas the shape of the peptide displays an $\alpha$--helix structure within the APP in its biologically active conformation. A realistic model of fibril formation is developed based on the seventeen residues A$\beta$12--28 amyloid peptide, which has been shown to form fibrils structurally similar to those of the whole A$\beta$ peptide. With the help of physical arguments and in keeping with experimental findings, the A$\beta$12--28 monomer is assumed to be in four possible states (i.e., native helix conformation, $\beta$--hairpin, globular low--energy state and unfolded state). Making use of these monomeric states, oligomers (dimers, tertramers and octamers) were constructed. With the help of short, detailed Molecular Dynamics (MD) calculations of the three monomers and of a variety of oligomers, energies for these structures were obtained. Making use of these results within the framework of a simple yet realistic model to describe the entropic terms associated with the variety of amyloid conformations, a phase diagram can be calculated of the whole many--body system, leading to a thermodynamical picture in overall agreement with the experimental findings. In particular, the existence of micellar metastable states seem to be a key issue to determine the thermodynamical properties of the system

Nature versus Nurture: The curved spine of the galaxy cluster X-ray luminosity -- temperature relation

The physical processes that define the spine of the galaxy cluster X-ray luminosity -- temperature (L-T) relation are investigated using a large hydrodynamical simulation of the Universe. This simulation models the same volume and phases as the Millennium Simulation and has a linear extent of 500 h^{-1} Mpc. We demonstrate that mergers typically boost a cluster along but also slightly below the L-T relation. Due to this boost we expect that all of the very brightest clusters will be near the peak of a merger. Objects from near the top of the L-T relation tend to have assembled much of their mass earlier than an average halo of similar final mass. Conversely, objects from the bottom of the relation are often experiencing an ongoing or recent merger.Comment: 8 pages, 7 figures, submitted to MNRA

Algorithms for Stable Matching and Clustering in a Grid

We study a discrete version of a geometric stable marriage problem originally proposed in a continuous setting by Hoffman, Holroyd, and Peres, in which points in the plane are stably matched to cluster centers, as prioritized by their distances, so that each cluster center is apportioned a set of points of equal area. We show that, for a discretization of the problem to an $n\times n$ grid of pixels with $k$ centers, the problem can be solved in time $O(n^2 \log^5 n)$, and we experiment with two slower but more practical algorithms and a hybrid method that switches from one of these algorithms to the other to gain greater efficiency than either algorithm alone. We also show how to combine geometric stable matchings with a $k$-means clustering algorithm, so as to provide a geometric political-districting algorithm that views distance in economic terms, and we experiment with weighted versions of stable $k$-means in order to improve the connectivity of the resulting clusters.Comment: 23 pages, 12 figures. To appear (without the appendices) at the 18th International Workshop on Combinatorial Image Analysis, June 19-21, 2017, Plovdiv, Bulgari

Minor structural modifications to alchemix influence mechanism of action and pharmacological activity

Alchemix is an exemplar of a class of anthraquinone with efficacy against multidrug resistant tumors. We have explored further the mechanism of action of alchemix and investigated the effect of extending its side arm bearing the alkylating functionality with regard to DNA binding and activity against multidrug resistant cancer cells. Increasing the distance between the intercalating chromophore and the alkylating functionality of ICT2901 (propyl), ICT2902 (butyl) and ICT2903 (pentyl), led to a higher number of DNA alkylation sites, more potent topoisomerase II inhibition and generated more apoptotic and necrotic cells when analysed in p53-proficient HCT116 cells. Intriguingly, alchemix, the compound with the shortest distance between its intercalative chromophore and alkylating functionality (ethyl), did not conform to this SAR. A different toxicity pattern against DNA repair defective CHO cell lines as well as arrest of cells in G1 supports a somewhat distinct mode of action by alchemix compared with its analogues. Importantly, both alchemix and ICT2901 demonstrated greater cytotoxic activity against anthraquinone-resistant MCF-7/adr cells than wild-type MCF-7 cells. Subtle synthetic modification in this anthraquinone series has led to significant changes to the stability of DNA-compound complexes and cellular activity. Given that the failure of chemotherapy in the clinic is often associated with MDR, the results of both alchemix and ICT2901 represent important advances towards improved therapies

Developing an On-Line Interactive Health Psychology Module.

On-line teaching material in health psychology was developed which ensured a range of students could access appropriate material for their course and level of study. This material has been developed around the concept of smaller 'content chunks' which can be combined into whole units of learning (topics), and ultimately, a module. On the basis of the underlying philosophy that the medium is part of the message, we considered interactivity to be a key element in engaging the student with the material. Consequently, the key aim of this development was to stimulate and engage students, promoting better involvement with the academic material, and hence better learning. It was hoped that this was achieved through the development of material including linked programmes and supporting material, small Java Scripts and basic email, forms and HTML additions. This material is outlined as are some of the interactive activities introduced, and the preliminary student and tutor experience described

MScMS-II: an innovative IR-based indoor coordinate measuring system for large-scale metrology applications

According to the current great interest concerning large-scale metrology applications in many different fields of manufacturing industry, technologies and techniques for dimensional measurement have recently shown a substantial improvement. Ease-of-use, logistic and economic issues, as well as metrological performance are assuming a more and more important role among system requirements. This paper describes the architecture and the working principles of a novel infrared (IR) optical-based system, designed to perform low-cost and easy indoor coordinate measurements of large-size objects. The system consists of a distributed network-based layout, whose modularity allows fitting differently sized and shaped working volumes by adequately increasing the number of sensing units. Differently from existing spatially distributed metrological instruments, the remote sensor devices are intended to provide embedded data elaboration capabilities, in order to share the overall computational load. The overall system functionalities, including distributed layout configuration, network self-calibration, 3D point localization, and measurement data elaboration, are discussed. A preliminary metrological characterization of system performance, based on experimental testing, is also presente

Covariant scalar representation of iosp(d,2/2)iosp(d,2/2) quantization of the scalar relativistic particle

A covariant scalar representation of $iosp(d,2/2)$ is constructed and analysed in comparison with existing methods for the quantization of the scalar relativistic particle. It is found that, with appropriately defined wavefunctions, this $iosp(d,2/2)$ produced representation can be identified with the state space arising from the canonical BFV-BRST quantization of the modular invariant, unoriented scalar particle (or antiparticle) with admissible gauge fixing conditions. For this model, the cohomological determination of physical states can thus be obtained purely from the representation theory of the $iosp(d,2/2)$ algebra.Comment: 16 pages Late

Long-range pollution transport during the MILAGRO-2006 campaign: a case study of a major Mexico City outflow event using free-floating altitude-controlled balloons

One of the major objectives of the Megacities Initiative: Local And Global Research Observations (MILAGRO-2006) campaign was to investigate the long-range transport of polluted Mexico City Metropolitan Area (MCMA) outflow and determine its downwind impacts on air quality and climate. Six research aircraft, including the National Center for Atmospheric Research (NCAR) C-130, made extensive chemical, aerosol, and radiation measurements above MCMA and more than 1000 km downwind in order to characterize the evolution of the outflow as it aged and dispersed over the Mesa Alta, Sierra Madre Oriental, Coastal Plain, and Gulf of Mexico. As part of this effort, free-floating Controlled-Meteorological (CMET) balloons, commanded to change altitude via satellite, made repeated profile measurements of winds and state variables within the advecting outflow. In this paper, we present an analysis of the data from two CMET balloons that were launched near Mexico City on the afternoon of 18 March 2006 and floated downwind with the MCMA pollution for nearly 30 h. The repeating profile measurements show the evolving structure of the outflow in considerable detail: its stability and stratification, interaction with other air masses, mixing episodes, and dispersion into the regional background. Air parcel trajectories, computed directly from the balloon wind profiles, show three transport pathways on 18–19 March: (a) high-altitude advection of the top of the MCMA mixed layer, (b) mid-level outflow over the Sierra Madre Oriental followed by decoupling and isolated transport over the Gulf of Mexico, and (c) low-level outflow with entrainment into a cleaner northwesterly jet above the Coastal Plain. The C-130 aircraft intercepted the balloon-based trajectories three times on 19 March, once along each of these pathways; in all three cases, peaks in urban tracer concentrations and LIDAR backscatter are consistent with MCMA pollution. In comparison with the transport models used in the campaign, the balloon-based trajectories appear to shear the outflow far more uniformly and decouple it from the surface, thus forming a thin but expansive polluted layer over the Gulf of Mexico that is well aligned with the aircraft observations. These results provide critical context for the extensive aircraft measurements made during the 18–19 March MCMA outflow event and may have broader implications for modelling and understanding long-range transport

Normal frames and the validity of the equivalence principle. III. The case along smooth maps with separable points of self-intersection

The equivalence principle is treated on a mathematically rigorous base on sufficiently general subsets of a differentiable manifold. This is carried out using the basis of derivations of the tensor algebra over that manifold. Necessary and/or sufficient conditions of existence, uniqueness, and holonomicity of these bases in which the components of the derivations of the tensor algebra over it vanish on these subsets, are studied. The linear connections are considered in this context. It is shown that the equivalence principle is identically valid at any point, and along any path, in every gravitational theory based on linear connections. On higher dimensional submanifolds it may be valid only in certain exceptional cases.Comment: 15 standard LaTeX 2e (11pt, A4) pages. The package amsfonts is require

A pp-adic RanSaC algorithm for stereo vision using Hensel lifting

A $p$-adic variation of the Ran(dom) Sa(mple) C(onsensus) method for solving the relative pose problem in stereo vision is developped. From two 2-adically encoded images a random sample of five pairs of corresponding points is taken, and the equations for the essential matrix are solved by lifting solutions modulo 2 to the 2-adic integers. A recently devised $p$-adic hierarchical classification algorithm imitating the known LBG quantisation method classifies the solutions for all the samples after having determined the number of clusters using the known intra-inter validity of clusterings. In the successful case, a cluster ranking will determine the cluster containing a 2-adic approximation to the "true" solution of the problem.Comment: 15 pages; typos removed, abstract changed, computation error remove