High-Performance Computing involves exploiting the capabilities of powerful computing resources to achieve high computational performance, efficiency, and scalability. By enabling to process complex tasks and/or large amounts of data efficiently, HPC plays an essential role in multiple domains. Parallelization and distribution of workloads across multiple processing resources is at the core of HPC and has been done via many approaches, including different programmatic models and service frameworks. In recent years, HPC has been coupled with Containerization, as a way to deploy, manage and run workloads in an automated and efficient manner, including those relying on accelerators. The performance of heterogeneous workloads, however, depends on the behavior of the platform scheduler, and of the mechanisms used to share accelerators, being also constraint by the limited number of accelerators that each node may host. This paper describes an approach by which the last limitation may be overcome, using a Kubernetes cluster as a show case. The approach builds on the integration of Kubernetes with rOpenCL, an OpenCL API forwarder for remote execution of OpenCL calls. This combination may also be particularly useful in Edge Computing scenarios, where containerized edge services gain the ability to access, transparently and efficiently, remote (e.g. cloud-based) accelerators. Some preliminary experimental results are presented, demonstrating the feasibility of this integration, and the impact on performance for an OpenCL application.

Nowadays, more and more services are dependent on the use of resources hosted on the web. The realization of operations such as access to the account bank, credit card operations, among other operations, is something increasingly common in current times, demonstrating not only human dependence on the internet connection, as well as the need to adapt the web resources to the daily life of society. As a result of this growing dependency, web resources now provide a greater amount of confidential information, making the risk of a cyberattack and information leaking grow considerably. In the web context, one of the most well-known attacks is SQL injection that allows the attacker to exploit, through the injection of malicious queries, access to confidential information. This paper suggests a solution for the detection of SQL injection via web resources, using the analysis of the logs of the executed queries.

In heterogeneous computing systems, general purpose CPUs are coupled with co-processors of different architectures, like GPUs and FPGAs. Applications may take advantage of this heterogeneous device ensemble to accelerate execution. However, developing heterogeneous applications requires specific programming models, under which applications unfold into code components targeting different computing devices. OpenCL is one of the main programming models for heterogeneous applications, set apart from others due to its openness, vendor independence and support for different co-processors. In the original OpenCL application model, a heterogeneous application starts in a certain host node, and then resorts to the local co-processors attached to that host. Therefore, co-processors at other nodes, networked with the host node, are inaccessible and cannot be used to accelerate the application. rOpenCL (remote OpenCL) overcomes this limitation for a significant set of the OpenCL 1.2 API, offering OpenCL applications transparent access to remote devices through a TPC/IP based network. This paper presents the architecture and the most relevant implementation details of rOpenCL, together with the results of a preliminary set of reference benchmarks. These prove the stability of the current prototype and show that, in many scenarios, the network overhead is smaller than expected.

SUMMARY: EasyModel is a new user-friendly web application that contains ready-for-simulation versions of the BioModels Database, and allows for the intuitive creation of new models. Its main target audience is the experimental biologist and students of bioinformatics or systems biology without programming skills. Expert users can also benefit from it by implementing basic models quickly and downloading the code for further tailoring. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at https://easymodel.udl.cat. Implementation is described in its own section.

The initial diagnosis of rare diseases is difficult because they are infrequent and doctors do not often see or recognize their symptoms. Developing tools to assist in this diagnosis would provide a way to facilitate medical practice in this area. The broader goal of this project is to develop such a tool, which we name rare disease discovery (http://disease-discovery.udl.cat). This tool is designed to identify rare diseases on the basis of a patient's symptoms. To create it, several software entities were designed and integrated. First, a database of symptoms associated with every human rare disease known was designed and implemented. This database was derived from information available from Orphanet. Orphanet provides gold-standard data regarding rare diseases in the world. Second, a user-friendly website was also designed, implemented, and connected to the database. This website connects the users, the database, and the third software entity, a disease prediction engine. Overall, we create an accurate, efficient, and user-friendly diagnosis tool that can be quickly learnt and handled by medical doctors for the prediction of rare diseases.

MOTIVATION: Chemical named entity recognition is used to automatically identify mentions to chemical compounds in text and is the basis for more elaborate information extraction. However, only a small number of applications are freely available to identify such mentions. Particularly challenging and useful is the identification of International Union of Pure and Applied Chemistry (IUPAC) chemical compounds, which due to the complex morphology of IUPAC names requires more advanced techniques than that of brand names. RESULTS: We present CheNER, a tool for automated identification of systematic IUPAC chemical mentions. We evaluated different systems using an established literature corpus to show that CheNER has a superior performance in identifying IUPAC names specifically, and that it makes better use of computational resources. AVAILABILITY AND IMPLEMENTATION: http://metres.udl.cat/index.php/9-download/4-chener, http://chener.bioinfo.cnio.es/

Biblio-MetReS is a single-thread data mining application that facilitates the reconstruction of molecular networks based on automated text mining analysis of published scientific literature. This application is very CPU-intensive, requiring High Performace Computing (HPC). Due to the amount of execution tasks, it can be quite slow. Those tasks are repetitive and consist in mining the information from large sets of scientific documents, a process where the time-cost of the application could be improved through paralellization.

BACKGROUND: Reconstruction of genes and/or protein networks from automated analysis of the literature is one of the current targets of text mining in biomedical research. Some user-friendly tools already perform this analysis on precompiled databases of abstracts of scientific papers. Other tools allow expert users to elaborate and analyze the full content of a corpus of scientific documents. However, to our knowledge, no user friendly tool that simultaneously analyzes the latest set of scientific documents available on line and reconstructs the set of genes referenced in those documents is available. RESULTS: This article presents such a tool, Biblio-MetReS, and compares its functioning and results to those of other user-friendly applications (iHOP, STRING) that are widely used. Under similar conditions, Biblio-MetReS creates networks that are comparable to those of other user friendly tools. Furthermore, analysis of full text documents provides more complete reconstructions than those that result from using only the abstract of the document. CONCLUSIONS: Literature-based automated network reconstruction is still far from providing complete reconstructions of molecular networks. However, its value as an auxiliary tool is high and it will increase as standards for reporting biological entities and relationships become more widely accepted and enforced. Biblio-MetReS is an application that can be downloaded from http://metres.udl.cat/. It provides an easy to use environment for researchers to reconstruct their networks of interest from an always up to date set of scientific documents.

Yeast successfully adapts to an environmental stress by altering physiology and fine-tuning metabolism. This fine-tuning is achieved through regulation of both gene expression and protein activity, and it is shaped by various physiological requirements. Such requirements impose a sustained evolutionary pressure that ultimately selects a specific gene expression profile, generating a suitable adaptive response to each environmental change. Although some of the requirements are stress specific, it is likely that others are common to various situations. We hypothesize that an evolutionary pressure for minimizing biosynthetic costs might have left signatures in the physicochemical properties of proteins whose gene expression is fine-tuned during adaptive responses. To test this hypothesis we analyze existing yeast transcriptomic data for such responses and investigate how several properties of proteins correlate to changes in gene expression. Our results reveal signatures that are consistent with a selective pressure for economy in protein synthesis during adaptive response of yeast to various types of stress. These signatures differentiate two groups of adaptive responses with respect to how cells manage expenditure in protein biosynthesis. In one group, significant trends towards downregulation of large proteins and upregulation of small ones are observed. In the other group we find no such trends. These results are consistent with resource limitation being important in the evolution of the first group of stress responses.

BACKGROUND: Understanding the relationship between gene expression changes, enzyme activity shifts, and the corresponding physiological adaptive response of organisms to environmental cues is crucial in explaining how cells cope with stress. For example, adaptation of yeast to heat shock involves a characteristic profile of changes to the expression levels of genes coding for enzymes of the glycolytic pathway and some of its branches. The experimental determination of changes in gene expression profiles provides a descriptive picture of the adaptive response to stress. However, it does not explain why a particular profile is selected for any given response. RESULTS: We used mathematical models and analysis of in silico gene expression profiles (GEPs) to understand how changes in gene expression correlate to an efficient response of yeast cells to heat shock. An exhaustive set of GEPs, matched with the corresponding set of enzyme activities, was simulated and analyzed. The effectiveness of each profile in the response to heat shock was evaluated according to relevant physiological and functional criteria. The small subset of GEPs that lead to effective physiological responses after heat shock was identified as the result of the tuning of several evolutionary criteria. The experimentally observed transcriptional changes in response to heat shock belong to this set and can be explained by quantitative design principles at the physiological level that ultimately constrain changes in gene expression. CONCLUSION: Our theoretical approach suggests a method for understanding the combined effect of changes in the expression of multiple genes on the activity of metabolic pathways, and consequently on the adaptation of cellular metabolism to heat shock. This method identifies quantitative design principles that facilitate understating the response of the cell to stress.

MOTIVATION: The method of mathematically controlled comparison has been used for some time to determine which of two alternative regulatory designs is better according to specific quantitative criteria for functional effectiveness. In some cases, the results obtained using this technique are general and independent of parameter values and the answers are clear-cut. In others, the result might be general, but the demonstration is difficult and numerical results with specific parameter values can help to clarify the situation. In either case, numerical results with specific parameter values can also provide an answer to the question of how much larger the values might be. In contrast, a more ambiguous result is obtained when either of the alternatives can have the larger value for a given systemic property, depending on the specific values of the parameters. In any case, introduction of specific values for the parameters reduces the generality of the results. Therefore, we have been motivated to develop and apply statistical methods that would permit the use of numerical values for the parameters and yet retain some of the generality that makes mathematically controlled comparison so attractive. RESULTS: We illustrate this new numerical method in a step-by-step application using a very simple didactic example. We also validate the results by comparison with the corresponding results obtained using the previously developed analytical method. The analytical approach is briefly present for reference purposes, since some of the same key concepts are needed to understand the numerical method and the results are needed for comparison. The numerical method confirms the qualitative differences between the systemic behavior of alternative designs obtained from the analytical method. In addition, the numerical method allows for quantification of the differences and it provides results that are general in a statistical sense. For example, the older analytical method showed that overall feedback inhibition in an unbranched pathway makes the system more robust whereas it decreases the stability margin of the steady state. The numerical method shows that the magnitudes of these differences are not comparable. The differences in stability margins (1-2% on average) are small when compared to the differences in robustness (50-100% on average). Furthermore, the numerical method shows that the system with overall feedback responds more quickly to change than the otherwise equivalent system without overall feedback. These results suggest reasons why overall feedback inhibition is such a prevalent regulatory pattern in unbranched biosynthetic pathways.

Abstract Motivation: When dealing with questions that concern a general class of models for biological networks, large numbers of distinct models within the class can be grouped into an ensemble that gives a statistical view of the properties for the general class. Comparing properties of different ensembles through the use of point measures (e.g. medians, standard deviations, correlation coefficients) can mask inhomogeneities in the correlations between properties. We are therefore motivated to develop strategies that allow these inhomogeneities to be more easily detected. Results: Methods are described for constructing ensembles of models within the context of a Mathematically Controlled Comparison. A Density of Ratios Plot for a given systemic property is then defined as follows: the \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(y\) \end{document}axis represents the value of the systemic property in a reference model divided by the value in the alternative model, and the \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(x\) \end{document}axis represents the value of the systemic property in the reference model. Techniques involving moving quantiles are introduced to generate secondary plots in which correlations and inhomogeneities in correlations are more easily detected. Several examples that illustrate the advantages of these techniques are presented and discussed. Contact: [email protected] * To whom correspondence should be addressed.

MOTIVATION: Mathematical models are the only realistic method for representing the integrated dynamic behavior of complex biochemical networks. However, it is difficult to obtain a consistent set of values for the parameters that characterize such a model. Even when a set of parameter values exists, the accuracy of the individual values is questionable. Therefore, we were motivated to explore statistical techniques for analyzing the properties of a given model when knowledge of the actual parameter values is lacking. RESULTS: The graphical and statistical methods presented in the previous paper are applied here to simple unbranched biosynthetic pathways subject to control by feedback inhibition. We represent these pathways within a canonical nonlinear formalism that provides a regular structure that is convenient for randomly sampling the parameter space. After constructing a large ensemble of randomly generated sets of parameter values, the structural and behavioral properties of the model with these parameter sets are examined statistically and classified. The results of our analysis demonstrate that certain properties of these systems are strongly correlated, thereby revealing aspects of organization that are highly probable independent of selection. Finally, we show how specification of a given behavior affects the distribution of acceptable parameter values.