Are Protein Folds Atypical?

Protein structures are a very special class among all possible structures. It was suggested that a ``designability principle'' plays a crucial role in nature's selection of protein sequences and structures. Here we provide a theoretical base for such a selection principle, using a novel formulation of the protein folding problem based on hydrophobic interactions. A structure is reduced to a string of 0's and 1's which represent the surface and core sites, respectively, as the backbone is traced. Each structure is therefore associated with one point in a high dimensional space. Sequences are represented by strings of their hydrophobicities and thus can be mapped into the same space. A sequence which lies closer to a particular structure in this space than to any other structures will have that structure as its ground state. Atypical structures, namely those far away from other structures in the high dimensional space, have more sequences which fold into them, and are thermodynamically more stable. We argue that the most common folds of proteins are the most atypical in the space of possible structures.Comment: 15 pages, 5 figure

Timed Automata Semantics for Analyzing Creol

We give a real-time semantics for the concurrent, object-oriented modeling language Creol, by mapping Creol processes to a network of timed automata. We can use our semantics to verify real time properties of Creol objects, in particular to see whether processes can be scheduled correctly and meet their end-to-end deadlines. Real-time Creol can be useful for analyzing, for instance, abstract models of multi-core embedded systems. We show how analysis can be done in Uppaal.Comment: In Proceedings FOCLASA 2010, arXiv:1007.499

Types for Location and Data Security in Cloud Environments

Cloud service providers are often trusted to be genuine, the damage caused by being discovered to be attacking their own customers outweighs any benefits such attacks could reap. On the other hand, it is expected that some cloud service users may be actively malicious. In such an open system, each location may run code which has been developed independently of other locations (and which may be secret). In this paper, we present a typed language which ensures that the access restrictions put on data on a particular device will be observed by all other devices running typed code. Untyped, compromised devices can still interact with typed devices without being able to violate the policies, except in the case when a policy directly places trust in untyped locations. Importantly, our type system does not need a middleware layer or all users to register with a preexisting PKI, and it allows for devices to dynamically create new identities. The confidentiality property guaranteed by the language is defined for any kind of intruder: we consider labeled bisimilarity i.e. an attacker cannot distinguish two scenarios that differ by the change of a protected value. This shows our main result that, for a device that runs well typed code and only places trust in other well typed devices, programming errors cannot cause a data leakage.Comment: Short version to appear in Computer Security Foundations Symposium (CSF'17), August 201

Exploiting Homology Information in Nontemplate Based Prediction of Protein Structures

In this paper we describe a novel strategy for exploring the conformational space of proteins and show that this leads to better models for proteins the structure of which is not amenable to template based methods. Our strategy is based on the assumption that the energy global minimum of homologous proteins must correspond to similar conformations, while the precise profiles of their energy landscape, and consequently the positions of the local minima, are likely to be different. In line with this hypothesis, we apply a replica exchange Monte Carlo simulation protocol that, rather than using different parameters for each parallel simulation, uses the sequences of homologous proteins. We show that our results are competitive with respect to alternative methods, including those producing the best model for each of the analyzed targets in the CASP10 (10th Critical Assessment of techniques for protein Structure Prediction) experiment free modeling category

Visible Volume: a Robust Measure for Protein Structure Characterization

We propose a new characterization of protein structure based on the natural tetrahedral geometry of the β carbon and a new geometric measure of structural similarity, called visible volume. In our model, the side-chains are replaced by an ideal tetrahedron, the orientation of which is fixed with respect to the backbone and corresponds to the preferred rotamer directions. Visible volume is a measure of the non-occluded empty space surrounding each residue position after the side-chains have been removed. It is a robust, parameter-free, locally-computed quantity that accounts for many of the spatial constraints that are of relevance to the corresponding position in the native structure. When computing visible volume, we ignore the nature of both the residue observed at each site and the ones surrounding it. We focus instead on the space that, together, these residues could occupy. By doing so, we are able to quantify a new kind of invariance beyond the apparent variations in protein families, namely, the conservation of the physical space available at structurally equivalent positions for side-chain packing. Corresponding positions in native structures are likely to be of interest in protein structure prediction, protein design, and homology modeling. Visible volume is related to the degree of exposure of a residue position and to the actual rotamers in native proteins. In this article, we discuss the properties of this new measure, namely, its robustness with respect to both crystallographic uncertainties and naturally occurring variations in atomic coordinates, and the remarkable fact that it is essentially independent of the choice of the parameters used in calculating it. We also show how visible volume can be used to align protein structures, to identify structurally equivalent positions that are conserved in a family of proteins, and to single out positions in a protein that are likely to be of biological interest. These properties qualify visible volume as a powerful tool in a variety of applications, from the detailed analysis of protein structure to homology modeling, protein structural alignment, and the definition of better scoring functions for threading purposes.National Library of Medicine (LM05205-13

Local area [pye]-calculus

All computers on the Internet are connected, but not all connections are equal. Hosts are grouped into islands of local communication. It is the agreed conventions and shared knowledge that connect these islands, just as much as the switches and wires that run between them. The power and limitation of these conventions and shared knowledge and hence their effectiveness can be investigated by an appropriate calculus. In this thesis I describe a development of the 7r-calculus that is particularly well suited to express such systems. The process calculus, which I call the local area n-calculus or Ian, extends the 7r-calculus so that a channel name can have within its scope several disjoint local areas. Such a channel name may be used for communication within an area or it may be sent between areas, but it cannot itself be used to transmit information from one area to another. Areas are arranged in a hierarchy of levels which distinguish, for example, between a single application, a machine, or a whole network. I present a semantics for this calculus that relies on several side-conditions which are essentially runtime level checks. I show that a suitable type system can provide enough static information to make most of these checks unnecessary. I examine the descriptive power of the /a7r-calculus by comparing it to the 7r-calculus. I find that, perhaps surprisingly, local area communication can be encoded into the 7T-calculus with conditional matching. The encoding works by replacing communication inside an area with communication on a new channel created just for that area. This is analogous to replacing direct communication between two points with a system that broadcasts packets over a background ether. I show a form of operational correspondence between the behaviour of a process in lan and its 7r-calculus translation. One of my aims in developing this calculus is to provide a convenient and ex¬ pressive framework with which to examine convention-laden, distributed systems. I offer evidence that the calculus has achieved this by way of an extended case study. I present a model of Internet communication based on Sockets and TCP over IP and then extend this system with Network Address Translation. I then 4 give a model of the File Transfer Protocol that uses TCP/IP to communicate between networks. Traces of the model show that FTP, run in its normal mode, will fail when the client is using Network Address Translation, whereas, an alternative mode of FTP will succeed. Moreover a normal run of the model over NAT fails in the same way as the real life system would, demonstrating that the model can pick up this failure and correctly highlight the reasons behind it

Geometrical model for the native-state folds of proteins

We recently introduced a physical model [Hoang et al., P. Natl. Acad. Sci. USA (2004), Banavar et al., Phys. Rev. E (2004)] for proteins which incorporates, in an approximate manner, several key features such as the inherent anisotropy of a chain molecule, the geometrical and energetic constraints placed by the hydrogen bonds and sterics, and the role played by hydrophobicity. Within this framework, marginally compact conformations resembling the native state folds of proteins emerge as broad competing minima in the free energy landscape even for a homopolymer. Here we show how the introduction of sequence heterogeneity using a simple scheme of just two types of amino acids, hydrophobic (H) and polar (P), and sequence design allows a selected putative native fold to become the free energy minimum at low temperature. The folding transition exhibits thermodynamic cooperativity, if one neglects the degeneracy between two different low energy conformations sharing the same fold topology.Comment: 12 pages, 3 figure

Geometry and symmetry presculpt the free-energy landscape of proteins

We present a simple physical model which demonstrates that the native state folds of proteins can emerge on the basis of considerations of geometry and symmetry. We show that the inherent anisotropy of a chain molecule, the geometrical and energetic constraints placed by the hydrogen bonds and sterics, and hydrophobicity are sufficient to yield a free energy landscape with broad minima even for a homopolymer. These minima correspond to marginally compact structures comprising the menu of folds that proteins choose from to house their native-states in. Our results provide a general framework for understanding the common characteristics of globular proteins.Comment: 23 pages, 5 figure

Encapsulating peritoneal sclerosis presenting with haemorrhagic ascites after transfer from peritoneal dialysis to haemodialysis

A patient with end-stage kidney disease due to chronic glomerulonephritis was initiated on continuous ambulatoryperitoneal dialysis. After three years he was transferred to haemodialysis following recurrent episodes of peritonitis.After the commencement of haemodialysis the patient developed progressive abdominal distension; paracentesisrevealed bloody ascites. Radiographic imaging revealed features of small bowel obstruction with bowel loops matted tothe posterior abdominal wall. A diagnosis of encapsulating peritoneal sclerosis was made. Treatment with prednisonewas initiated but the patients condition steadily worsened and he demised a year later due to severe malnutrition andsepsis