BackgroundThe default-mode network (DMN) is a functional network with increasing relevance for psychiatric research, characterized by increased activation at rest and decreased activation during task performance. The degree of DMN deactivation during a cognitively demanding task depends on its difficulty. However, the relation of hemodynamic responses in the resting phase after a preceding cognitive challenge remains relatively unexplored. We test the hypothesis that the degree of activation of the DMN following cognitive challenge is influenced by the cognitive load of a preceding working-memory task.Methodology/Principal FindingsTwenty-five healthy subjects were investigated with functional MRI at 3 Tesla while performing a working-memory task with embedded short resting phases. Data were decomposed into statistically independent spatio-temporal components using Tensor Independent Component Analysis (TICA). The DMN was selected using a template-matching procedure. The spatial map contained rest-related activations in the medial frontal cortex, ventral anterior and posterior cingulate cortex. The time course of the DMN revealed increased activation at rest after 1-back and 2-back blocks compared to the activation after a 0-back block.Conclusion/SignificanceWe present evidence that a cognitively challenging working-memory task is followed by greater activation of the DMN than a simple letter-matching task. This might be interpreted as a functional correlate of self-evaluation and reflection of the preceding task or as relocation of cerebral resources representing recovery from high cognitive demands. This finding is highly relevant for neuroimaging studies which include resting phases in cognitive tasks as stable baseline conditions. Further studies investigating the DMN should take possible interactions of tasks and subsequent resting phases into account.

Cloud computing offers massively scalable, elastic resources (e.g., data, computing power, and services) over the internet from remote data centres to the consumers. The growing market penetration, with an evermore diverse provider and service landscape, turns Cloud computing marketplaces a highly competitive one. In this highly competitive and distributed service environment, the assurances are insufficient for the consumers to identify the dependable and trustworthy Cloud providers. This paper provides a landscape and discusses incentives and hindrances to adopt Cloud computing from Cloud consumers' perspective. Due to these hindrances, potential consumers are not sure whether they can trust the Cloud providers in offering dependable services. Trust-aided unified evaluation framework by leveraging trust and reputation systems can be used to assess trustworthiness (or dependability) of Cloud providers. Hence, cloud-related specific parameters (QoS+) are required for the trust and reputation systems in Cloud environments. We identify the essential properties and corresponding research challenges to integrate the QoS+ parameters into trust and reputation systems. Finally, we survey and analyse the existing trust and reputation systems in various application domains, characterizing their individual strengths and weaknesses. Our work contributes to understanding 1) why trust establishment is important in the Cloud computing landscape, 2) how trust can act as a facilitator in this context and 3) what are the exact requirements for trust and reputation models (or systems) to support the consumers in establishing trust on Cloud providers.

Abstract. Solutions calculated by Evolutionary Algorithms have come to surpass exact methods for solving various problems. The Rubik's Cube multiobjective optimization problem is one such area. In this work we present an evolutionary approach to solve the Rubik's Cube with a low number of moves by building upon the classic Thistlethwaite's approach. We provide a group theoretic analysis of the subproblem complexity induced by Thistlethwaite's group transitions and design an Evolutionary Algorithm from the ground up including detailed derivation of our custom fitness functions. The implementation resulting from these observations is thoroughly tested for integrity and random scrambles, revealing performance that is competitive with exact methods without the need for pre-calculated lookup-tables.

In this study we used a Random Forest-based approach for an assignment of small guanosine triphosphate proteins (GTPases) to specific subgroups. Small GTPases represent an important functional group of proteins that serve as molecular switches in a wide range of fundamental cellular processes, including intracellular transport, movement and signaling events. These proteins have further gained a special emphasis in cancer research, because within the last decades a huge variety of small GTPases from different subgroups could be related to the development of all types of tumors. Using a random forest approach, we were able to identify the most important amino acid positions for the classification process within the small GTPases superfamily and its subgroups. These positions are in line with the results of earlier studies and have been shown to be the essential elements for the different functionalities of the GTPase families. Furthermore, we provide an accurate and reliable software tool (GTPasePred) to identify potential novel GTPases and demonstrate its application to genome sequences.

BackgroundMaturation inhibitors such as Bevirimat are a new class of antiretroviral drugs that hamper the cleavage of HIV-1 proteins into their functional active forms. They bind to these preproteins and inhibit their cleavage by the HIV-1 protease, resulting in non-functional virus particles. Nevertheless, there exist mutations in this region leading to resistance against Bevirimat. Highly specific and accurate tools to predict resistance to maturation inhibitors can help to identify patients, who might benefit from the usage of these new drugs.ResultsWe tested several methods to improve Bevirimat resistance prediction in HIV-1. It turned out that combining structural and sequence-based information in classifier ensembles led to accurate and reliable predictions. Moreover, we were able to identify the most crucial regions for Bevirimat resistance computationally, which are in line with experimental results from other studies.ConclusionsOur analysis demonstrated the use of machine learning techniques to predict HIV-1 resistance against maturation inhibitors such as Bevirimat. New maturation inhibitors are already under development and might enlarge the arsenal of antiretroviral drugs in the future. Thus, accurate prediction tools are very useful to enable a personalized therapy.