Generalized Strong Curvature Singularities and Cosmic Censorship

A new definition of a strong curvature singularity is proposed. This definition is motivated by the definitions given by Tipler and Krolak, but is significantly different and more general. All causal geodesics terminating at these new singularities, which we call generalized strong curvature singularities, are classified into three possible types; the classification is based on certain relations between the curvature strength of the singularities and the causal structure in their neighborhood. A cosmic censorship theorem is formulated and proved which shows that only one class of generalized strong curvature singularities, corresponding to a single type of geodesics according to our classification, can be naked. Implications of this result for the cosmic censorship hypothesis are indicated.Comment: LaTeX, 11 pages, no figures, to appear in Mod. Phys. Lett.

A Rough Set-Based Model of HIV-1 Reverse Transcriptase Resistome

Reverse transcriptase (RT) is a viral enzyme crucial for HIV-1 replication. Currently, 12 drugs are targeted against the RT. The low fidelity of the RT-mediated transcription leads to the quick accumulation of drug-resistance mutations. The sequence-resistance relationship remains only partially understood. Using publicly available data collected from over 15 years of HIV proteome research, we have created a general and predictive rule-based model of HIV-1 resistance to eight RT inhibitors. Our rough set-based model considers changes in the physicochemical properties of a mutated sequence as compared to the wild-type strain. Thanks to the application of the Monte Carlo feature selection method, the model takes into account only the properties that significantly contribute to the resistance phenomenon. The obtained results show that drug-resistance is determined in more complex way than believed. We confirmed the importance of many resistance-associated sites, found some sites to be less relevant than formerly postulated and—more importantly—identified several previously neglected sites as potentially relevant. By mapping some of the newly discovered sites on the 3D structure of the RT, we were able to suggest possible molecular-mechanisms of drug-resistance. Importantly, our model has the ability to generalize predictions to the previously unseen cases. The study is an example of how computational biology methods can increase our understanding of the HIV-1 resistome

Implementation of the Vectorized Position-Specific Iterated Smith-Waterman Algorithm with Heuristic Filtering Algorithm on Cray Architecture

ABSTRACT: Smith-Waterman is the algorithm for finding local optimal alignments of two amino acid sequences, but is too slow for use in regular large database scanning. We have implemented SW algorithm on Cray X1 architecture, exploiting vectorization and parallelization. In addition we have proposed heuristic database filtering algorithm, which is particularly well suited for the Cray architecture, exploiting possibilities given by the BMM unit

The need for standardisation in life science research - an approach to excellence and trust

Today, academic researchers benefit from the changes driven by digital technologies and the enormous growth of knowledge and data, on globalisation, enlargement of the scientific community, and the linkage between different scientific communities and the society. To fully benefit from this development, however, information needs to be shared openly and transparently. Digitalisation plays a major role here because it permeates all areas of business, science and society and is one of the key drivers for innovation and international cooperation. To address the resulting opportunities, the EU promotes the development and use of collaborative ways to produce and share knowledge and data as early as possible in the research process, but also to appropriately secure results with the European strategy for Open Science (OS). It is now widely recognised that making research results more accessible to all societal actors contributes to more effective and efficient science; it also serves as a boost for innovation in the public and private sectors. However for research data to be findable, accessible, interoperable and reusable the use of standards is essential. At the metadata level, considerable efforts in standardisation have already been made (e.g. Data Management Plan and FAIR Principle etc.), whereas in context with the raw data these fundamental efforts are still fragmented and in some cases completely missing. The CHARME consortium, funded by the European Cooperation in Science and Technology (COST) Agency, has identified needs and gaps in the field of standardisation in the life sciences and also discussed potential hurdles for implementation of standards in current practice. Here, the authors suggest four measures in response to current challenges to ensure a high quality of life science research data and their re-usability for research and innovation