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Automatic tendencies to approach addictionrelated stimuli have been linked to the development and maintenance of harmful drug use behavior. Recent studies have shown that these automatic approaches can be directly addressed and modified by cognitive bias modification (CBM). However, the training and treatment effects are rather small and compliance could be impaired by time-consuming, multiple laboratory training sessions. Here we present a mobile variant of the Approach-Avoidance Task (app-AAT), which is evaluated by a feasibility study. The app-AAT is designed to improve the efficiency of CBM training by allowing smokers to access the training at any time, and by offering the option to track consumed cigarettes. Our first run with eight participants showed that the app was rated very positively with 4.2 out of 5 points (engagement: 3.7, functionality: 4.5, aesthetics: 4.4) by using the german Mobile App Rating Scale (MARS-G).

BACKGROUND: Many organizations are undertaking efforts to reduce the stress of (oftentimes overworked) employees. Information Technology (IT) (e.g., smartphones) has the potential to be a key instrument for reducing stress. One design-relevant factor considered to reduce stress is the concept of autonomy. Unfortunately, little research exists using autonomy as a characteristic of technology design. OBJECTIVE: Against this background, this study aimed to investigate specific autonomy-related design options with the potential to prevent stress. METHODS: In a factorial survey, this experimental study tested three design options in an overwork scenario: 1) autonomy (no intervention by design), 2) nudge ("nudging" by design), and 3) enforcement (hard stop by design). 51 participants (mean age 38 years, 50% women, mean work experience 18 years) from the Netherlands, United Kingdom, United States of America, and Germany participated in the experiment for 330 seconds on average. To test our hypothesis, we used a two-step approach. First, a multiple linear regression was applied. Second, we carried out a one-way ANCOVA comparing the effects of our design options. RESULTS: Our results indicate that autonomy can be manipulated through technology design and is negatively correlated with stress. Additionally, the design options autonomy and nudge were associated with lower levels of perceived stress than was enforcement. CONCLUSION: The study proposes a careful use of IT and policies that limit the perceived autonomy of employees. Overall, this study offers a set of design recommendations arguing that organizations should implement technology that helps employees prevent overwork and maintain their autonomy. [ABSTRACT FROM AUTHOR]

Purpose: Immersive virtual reality (IVR) has been frequently proposed as a promising tool for learning. However, researchers have commonly implemented a plethora of design elements in these IVR systems, which makes the specific aspects of the system that are necessary to achieve beneficial outcomes unclear. Against this background, this study aims to combine the literature on presence with learning theories to propose that the ability of IVR to present 3D objects to users improves the presence of these objects in the virtual environment compared with 2D objects, leading to increased learning performance. Design/methodology/approach: To test this study's hypotheses, the authors conducted a 2 (training condition: approach vs avoid) x 2 (object presence: high vs low) between-subjects laboratory experiment that used IVR with 83 female participants. Findings: The results support this study's hypotheses and show that training with high object presence leads to greater reactions to cues (chocolate cravings) and improved health behaviour (chocolate consumption). Originality/value: This study shows that increased object presence leads to unique experiences for users, which help reinforce training effects. Moreover, this work sheds further light on how immersive computer technologies can affect user attitudes and behaviour. Specifically, this work contributes to IVR research by showing that learning effects can be enhanced through an increased degree of object presence. [ABSTRACT FROM AUTHOR]

Tumour progression is an evolutionary process in which different clones evolve over time, leading to intra-tumour heterogeneity. Interactions between clones can affect tumour evolution and hence disease progression and treatment outcome. Intra-tumoural pairs of mutations that are overrepresented in a co-occurring or clonally exclusive fashion over a cohort of patient samples may be suggestive of a synergistic effect between the different clones carrying these mutations. We therefore developed a novel statistical testing framework, called GeneAccord, to identify such gene pairs that are altered in distinct subclones of the same tumour. We analysed our framework for calibration and power. By comparing its performance to baseline methods, we demonstrate that to control type I errors, it is essential to account for the evolutionary dependencies among clones. In applying GeneAccord to the single-cell sequencing of a cohort of 123 acute myeloid leukaemia patients, we find 1 clonally co-occurring and 8 clonally exclusive gene pairs. The clonally exclusive pairs mostly involve genes of the key signalling pathways. Author summary: Tumours typically display high levels of heterogeneity, not only between different tumours but also within a single one. Intra-tumour heterogeneity results from an evolutionary process, giving rise to different populations of cancer cells known as clones. How clones interact may affect tumour evolution, which in turn determines disease progression and treatment outcome. In practice, we may observe pairs of mutations that co-occur in clones or exclude each other more often than we would expect for a given cohort of patient samples. Exclusive pairs are suggestive that clones carrying one or the other mutation may cooperate in the evolutionary process. Targeting only one of them may then suffice to alter the tumour evolution. Therefore it is critical to have statistical methods which allow us to identify such pairs. GeneAccord is a novel statistical testing framework we developed especially to identify pairs of genes altered in distinct clones of the same tumour. Accounting for the evolutionary dependencies among clones emerged as critical to adequately control testing errors. In a cohort of 123 acute myeloid leukaemia patients, GeneAccord identified one clonally co-occurring and eight clonally exclusive gene pairs. The latter predominantly involved genes of key signalling pathways. [ABSTRACT FROM AUTHOR]

Abstract Background The center string (or closest string) problem is a classic computer science problem with important applications in computational biology. Given k input strings and a distance threshold d, we search for a string within Hamming distance at most d to each input string. This problem is NP complete. Results In this paper, we focus on exact methods for the problem that are also swift in application. We first introduce data reduction techniques that allow us to infer that certain instances have no solution, or that a center string must satisfy certain conditions. We describe how to use this information to speed up two previously published search tree algorithms. Then, we describe a novel iterative search strategy that is effecient in practice, where some of our reduction techniques can also be applied. Finally, we present results of an evaluation study for two different data sets from a biological application. Conclusions We find that the running time for computing the optimal center string is dominated by the subroutine calls for d = dopt -1 and d = dopt. Our data reduction is very effective for both, either rejecting unsolvable instances or solving trivial positions. We find that this speeds up computations considerably.

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The question of the optimal level of diversification in marketing research has a long history and shows an inconsistent empirical picture. Based on assumptions from the media management field, consumer engagement literature and social identity approach, this paper is aimed at obtaining a better understanding of diversification as a competitive advantage for organizations in eSports. Accordingly, we collected a sample of 216 League of Legends consumers, via the crowdsourcing marketplace Mechanical Turk- to explain the phenomenon of customer loyalty' for different eSports franchises. Using a quasi-experimental approach and structural equation modeling, our results show support for an inverted u-shaped curve of diversification. Medium diversified franchises seem to have the most beneficial positions in the eSports market. Furthermore, our holistic model illustrates that franchise identification has the potential to explain media engagement. Additionally, the two dimensions of media engagement – consumption and contribution – affect franchise loyalty in a positive manner, contrary to the third-dimension creation. We further discuss the contributions of our analyses and identify potential paths for future research in this paper. [ABSTRACT FROM AUTHOR]

Background: Comparative analyses of chromosomal gene orders are successfully used to predict gene clusters in bacterial and fungal genomes. Present models for detecting sets of co-localized genes in chromosomal sequences require prior knowledge of gene family assignments of genes in the dataset of interest. These families are often computationally predicted on the basis of sequence similarity or higher order features of gene products. Errors introduced in this process amplify in subsequent gene order analyses and thus may deteriorate gene cluster prediction. Results: In this work, we present a new dynamic model and efficient computational approaches for gene cluster prediction suitable in scenarios ranging from traditional gene family-based gene cluster prediction, via multiple conflicting gene family annotations, to gene family-free analysis, in which gene clusters are predicted solely on the basis of a pairwise similarity measure of the genes of different genomes. We evaluate our gene family-free model against a gene family-based model on a dataset of 93 bacterial genomes. Conclusions: Our model is able to detect gene clusters that would be also detected with well-established gene family-based approaches. Moreover, we show that it is able to detect conserved regions which are missed by gene family-based methods due to wrong or deficient gene family assignments. [ABSTRACT FROM AUTHOR]

Background: Genes occurring co-localized in multiple genomes can be strong indicators for either functional constraints on the genome organization or remnant ancestral gene order. The computational detection of these patterns, which are usually referred to as gene clusters, has become increasingly sensitive over the past decade. The most powerful approaches allow for various types of imperfect cluster conservation: Cluster locations may be internally rearranged. The individual cluster locations may contain only a subset of the cluster genes and may be disrupted by uninvolved genes. Moreover cluster locations may not at all occur in some or even most of the studied genomes. The detection of such low quality clusters increases the risk of mistaking faint patterns that occur merely by chance for genuine findings. Therefore, it is crucial to estimate the significance of computational gene cluster predictions and discriminate between true conservation and coincidental clustering. Results: In this paper, we present an efficient and accurate approach to estimate the significance of gene cluster predictions under the approximate common intervals model. Given a single gene cluster prediction, we calculate the probability to observe it with the same or a higher degree of conservation under the null hypothesis of random gene order, and add a correction factor to account for multiple testing. Our approach considers all parameters that define the quality of gene cluster conservation: the number of genomes in which the cluster occurs, the number of involved genes, the degree of conservation in the different genomes, as well as the frequency of the clustered genes within each genome. We apply our approach to evaluate gene cluster predictions in a large set of well annotated genomes. [ABSTRACT FROM AUTHOR]

Background: It has recently been shown that fractionation, the random loss of excess gene copies after a whole genome duplication event, is a major cause of gene order disruption. When estimating evolutionary distances between genomes based on chromosomal rearrangement, fractionation inevitably leads to significant overestimation of classic rearrangement distances. This bias can be largely avoided when genomes are preprocessed by "consolidation", a procedure that identifies and accounts for regions of fractionation. Results: In this paper, we present a new consolidation algorithm that extends and improves previous work in several directions. We extend the notion of the fractionation region to use information provided by regions where this process is still ongoing. The new algorithm can optionally work with this new definition of fractionation region and is able to process not only tetraploids but also genomes that have undergone hexaploidization and polyploidization events of higher order. Finally, this algorithm reduces the asymptotic time complexity of consolidation from quadratic to linear dependence on the genome size. The new algorithm is applied both to plant genomes and to simulated data to study the effect of fractionation in ancient hexaploids. [ABSTRACT FROM AUTHOR]

Background: Mancheron, Uricaru and Rivals (Nucleic Acids Res. 39:e101, 2011) recently introduced a new approach in the context of multiple genome comparison that allows to detect regions of strong overlaps in a set of pairwise local alignments between several reference genomes and one target genome. Such overlap regions are an important source of information in genome annotation. Results: In this paper we introduce a series of algorithms that improve over the approach of Mancheron et al., both in terms of computational complexity and in practical runtime. We also extend the problem definition such that overlaps to different reference genomes can be rated differently and regions overlapping only a subset of the reference genomes are detected. [ABSTRACT FROM AUTHOR]

Whole genome comparison based on the analysis of gene cluster conservation has become a popular approach in comparative genomics. While gene order and gene content as a whole randomize over time, it is observed that certain groups of genes which are often functionally related remain co-located across species. However, the conservation is usually not perfect which turns the identification of these structures, often referred to as approximate gene clusters, into a challenging task. In this article, we present an efficient set distance based approach that computes approximate gene clusters by means of reference occurrences. We show that it yields highly comparable results to the corresponding non-reference based approach, while its polynomial runtime allows for approximate gene cluster detection in parameter ranges that used to be feasible only with simpler, e.g., max-gap based, gene cluster models. To illustrate further the performance and predictive power of our algorithm, we compare it to a state-of-the art approach for max-gap gene cluster computation. [ABSTRACT FROM AUTHOR]

Background: The center string (or closest string) problem is a classic computer science problem with important applications in computational biology. Given k input strings and a distance threshold d, we search for a string within Hamming distance at most d to each input string. This problem is NP complete. Results: In this paper, we focus on exact methods for the problem that are also swift in application. We first introduce data reduction techniques that allow us to infer that certain instances have no solution, or that a center string must satisfy certain conditions. We describe how to use this information to speed up two previously published search tree algorithms. Then, we describe a novel iterative search strategy that is effecient in practice, where some of our reduction techniques can also be applied. Finally, we present results of an evaluation study for two different data sets from a biological application. Conclusions: We find that the running time for computing the optimal center string is dominated by the subroutine calls for d = dopt -1 and d = dopt. Our data reduction is very effective for both, either rejecting unsolvable instances or solving trivial positions. We find that this speeds up computations considerably. [ABSTRACT FROM AUTHOR]

Germinal centers (GCs) are specialized compartments within the secondary lymphoid organs where B cells proliferate, differentiate, and mutate their antibody genes in response to the presence of foreign antigens. Through the GC lifespan, interclonal competition between B cells leads to increased affinity of the B cell receptors for antigens accompanied by a loss of clonal diversity, although the mechanisms underlying clonal dynamics are not completely understood. We present here a multi-scale quantitative model of the GC reaction that integrates an intracellular component, accounting for the genetic events that shape B cell differentiation, and an extracellular stochastic component, which accounts for the random cellular interactions within the GC. In addition, B cell receptors are represented as sequences of nucleotides that mature and diversify through somatic hypermutations. We exploit extensive experimental characterizations of the GC dynamics to parameterize our model, and visualize affinity maturation by means of evolutionary phylogenetic trees. Our explicit modeling of B cell maturation enables us to characterise the evolutionary processes and competition at the heart of the GC dynamics, and explains the emergence of clonal dominance as a result of initially small stochastic advantages in the affinity to antigen. Interestingly, a subset of the GC undergoes massive expansion of higher-affinity B cell variants (clonal bursts), leading to a loss of clonal diversity at a significantly faster rate than in GCs that do not exhibit clonal dominance. Our work contributes towards an in silico vaccine design, and has implications for the better understanding of the mechanisms underlying autoimmune disease and GC-derived lymphomas. [ABSTRACT FROM AUTHOR]

Understanding the clonal architecture and evolutionary history of a tumour poses one of the key challenges to overcome treatment failure due to resistant cell populations. Previously, studies on subclonal tumour evolution have been primarily based on bulk sequencing and in some recent cases on single-cell sequencing data. Either data type alone has shortcomings with regard to this task, but methods integrating both data types have been lacking. Here, we present B-SCITE, the first computational approach that infers tumour phylogenies from combined single-cell and bulk sequencing data. Using a comprehensive set of simulated data, we show that B-SCITE systematically outperforms existing methods with respect to tree reconstruction accuracy and subclone identification. B-SCITE provides high-fidelity reconstructions even with a modest number of single cells and in cases where bulk allele frequencies are affected by copy number changes. On real tumour data, B-SCITE generated mutation histories show high concordance with expert generated trees. Intra-tumour heterogeneity provides important information about subclonal tumour evolution. Here, the authors develop B-SCITE, a computational method for inferring tumour phylogenies from combined single-cell and bulk sequencing data. [ABSTRACT FROM AUTHOR]