IT University of Copenhagen

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother–father–child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10−8 per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research. This issue of Nature contains the first publication from The 1000 Genomes Project, an international collaboration that will produce an extensive public catalogue of human genetic variation. The plan, in fact, is to sequence about 2,000 unidentified individuals from 20 populations around the world. This first paper presents the results from the project's pilot phase, testing three different strategies for genome-wide sequencing with high-throughput platforms: low-coverage whole-genome sequencing of 179 individuals in three population groups, high-coverage sequencing of two mother–father–child trios, and exon-targeted sequencing of 697 individuals from seven populations. The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Recent years have seen a rapid proliferation of mass-market consumer software that takes inspiration from video games. Usually summarized as "gamification", this trend connects to a sizeable body of existing concepts and research in human-computer interaction and game studies, such as serious games, pervasive games, alternate reality games, or playful design. However, it is not clear how "gamification" relates to these, whether it denotes a novel phenomenon, and how to define it. Thus, in this paper we investigate "gamification" and the historical origins of the term in relation to precursors and similar concepts. It is suggested that "gamified" applications provide insight into novel, gameful phenomena complementary to playful phenomena. Based on our research, we propose a definition of "gamification" as the use of game design elements in non-game contexts.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

"Gamification" is an informal umbrella term for the use of video game elements in non-gaming systems to improve user experience (UX) and user engagement. The recent introduction of 'gamified' applications to large audiences promises new additions to the existing rich and diverse research on the heuristics, design patterns and dynamics of games and the positive UX they provide. However, what is lacking for a next step forward is the integration of this precise diversity of research endeavors. Therefore, this workshop brings together practitioners and researchers to develop a shared understanding of existing approaches and findings around the gamification of information systems, and identify key synergies, opportunities, and questions for future research.

Despite active research and significant progress in the last 30 years, eye detection and tracking remains challenging due to the individuality of eyes, occlusion, variability in scale, location, and light conditions. Data on eye location and details of eye movements have numerous applications and are essential in face detection, biometric identification, and particular human-computer interaction tasks. This paper reviews current progress and state of the art in video-based eye detection and tracking in order to identify promising techniques as well as issues to be further addressed. We present a detailed review of recent eye models and techniques for eye detection and tracking. We also survey methods for gaze estimation and compare them based on their geometric properties and reported accuracies. This review shows that, despite their apparent simplicity, the development of a general eye detection technique involves addressing many challenges, requires further theoretical developments, and is consequently of interest to many other domains problems in computer vision and beyond.

This article examines five common misunderstandings about case-study research: (a) theoretical knowledge is more valuable than practical knowledge; (b) one cannot generalize from a single case, therefore, the single-case study cannot contribute to scientific development; (c) the case study is most useful for generating hypotheses, whereas other methods are more suitable for hypotheses testing and theory building; (d) the case study contains a bias toward verification; and (e) it is often difficult to summarize specific case studies. This article explains and corrects these misunderstandings one by one and concludes with the Kuhnian insight that a scientific discipline without a large number of thoroughly executed case studies is a discipline without systematic production of exemplars, and a discipline without exemplars is an ineffective one. Social science may be strengthened by the execution of a greater number of good case studies.La version espanola de este articulo se puede encontrar en: http://www.ssrn.com/abstract=2278291Den danske version af denne artikel kan findes pa: http://www.ssrn.com/abstract=2278229Den Svenska versionen av denna artikel finns pa: http://www.ssrn.com/abstract=2278403Polska wersja tego artykulu znajduje sie tutaj: http://www.ssrn.com/abstract=2278318Listed as Most Read and Most Cited paper on the journal's home page.

This article reflects the kinds of situations and spaces where people and algorithms meet. In what situations do people become aware of algorithms? How do they experience and make sense of these algorithms, given their often hidden and invisible nature? To what extent does an awareness of algorithms affect people's use of these platforms, if at all? To help answer these questions, this article examines people's personal stories about the Facebook algorithm through tweets and interviews with 25 ordinary users. To understand the spaces where people and algorithms meet, this article develops the notion of the algorithmic imaginary. It is argued that the algorithmic imaginary – ways of thinking about what algorithms are, what they should be and how they function – is not just productive of different moods and sensations but plays a generative role in moulding the Facebook algorithm itself. Examining how algorithms make people feel, then, seems crucial if we want to understand their social power.

Lipopeptides constitute a structurally diverse group of metabolites produced by various bacterial and fungal genera. In the past decades, research on lipopeptides has been fueled by their antimicrobial, antitumour, immunosuppressant and surfactant activities. However, the natural functions of lipopeptides in the lifestyles of the producing microorganisms have received considerably less attention. The substantial structural diversity of lipopeptides suggests that these metabolites have different natural roles, some of which may be unique to the biology of the producing organism. This review gives a detailed overview of the versatile functions of lipopeptides in the biology of Pseudomonas and Bacillus species, and highlights their role in competitive interactions with coexisting organisms, including bacteria, fungi, oomycetes, protozoa, nematodes and plants. Their functions in cell motility, leading to colonization of novel habitats, and in the formation and development of highly structured biofilms are discussed in detail. Finally, this review provides an update on lipopeptide detection and discovery as well as on novel regulatory mechanisms and genes involved in lipopeptide biosynthesis in these two bacterial genera.

Macroscopic organic aggregates, which are > 500 m and known as marine and lake snow, are important components in the turnover, decomposition and sinking flux of both organic and inorganic matter and elements in aquatic ecosystems. They are composed of various organic and inorganic materials depending largely on the given system and environmental conditions. The systems include the pelagic limnetic, the neritic and oceanic marine region, as well as shallow turbid environments, e.g. rivers, the littoral zone of lakes, estuaries and tidally affected coastal areas with intense turbulence and a high load of suspended matter. Aggregate abundance and size vary greatly among these systems. Macroaggregates are heavily colonized by bacteria and other heterotrophic microbes and greatly enriched in organic and inorganic nutrients as compared to the surrounding water. During the last 15 yr, many studies have been carried out to examine various aspects of the formation of aggregates, their microbial colonization and decomposition, nutrient recycling and their significance for the sinking flux. They have been identified as hot-spots of the microbial decomposition of organic matter. Further, microaggregates, which are < 5 to 500 m in size and stained by different dyes, such as transparent exopolymer particles (TEP) and Coomassie blue-stained particles, have been discovered and shown also to be important in the formation and decomposition of macroaggregates. In this review we give an overview of the present state of the microbial ecology of macro-and microaggregates, including the mentioned points but highlighting in particular the recent findings on the bacterial colonization of aggregates using molecular tools, their microbial decomposition and mineralization, and the significance of protozoans and metazoans for the colonization and decomposition of macroaggregates. Today it is evident that not only the aggregates but also their surroundings are sites and hot-spots of microbial processes, with the plume of solutes leaking out of the aggregates and greatly extending the volume of the intense decomposition processes. This microheterogeneity has important implications for the spatial and temporal dynamics of the organic-matter field in aquatic ecosystems and for our understanding of how heterotrophic organisms are involved in the decomposition of organic matter. The significance of aggregate-associated microbial processes as key processes and also for the overall decomposition and flux of organic mattervaries greatly among the various systems, and is greatly affected by the total amount of suspended particulate matter. A conclusion from the presented studies and results is that the significance of bacteria for the formation and decomposition of aggregates appears to be much greater than previously estimated. For a better understanding of the functioning of aquatic ecosystems it is of great importance to include aggregate-associated processes in ecosystem modeling approaches.

Abstract IF … THEN provides an account of power and politics in the algorithmic media landscape that pays attention to the multiple realities of algorithms, and how these relate and coexist. The argument is made that algorithms do not merely have power and politics; they help to produce certain forms of acting and knowing in the world. In processing, classifying, sorting, and ranking data, algorithms are political in that they help to make the world appear in certain ways rather than others. Analyzing Facebook’s news feed, social media user’s everyday encounters with algorithmic systems, and the discourses and work practices of news professionals, the book makes a case for going beyond the narrow, technical definition of algorithms as step-by-step procedures for solving a problem in a finite number of steps. Drawing on a process-relational theoretical framework and empirical data from field observations and fifty-five interviews, the author demonstrates how algorithms exist in multiple ways beyond code. The analysis is concerned with the world-making capacities of algorithms, questioning how algorithmic systems shape encounters and orientations of different kinds, and how these systems are endowed with diffused personhood and relational agency. IF … THEN argues that algorithmic power and politics is neither about algorithms determining how the social world is fabricated nor about what algorithms do per se. Rather it is about how and when different aspects of algorithms and the algorithmic become available to specific actors, under what circumstance, and who or what gets to be part of how algorithms are defined.

The contribution of psychological disorders to the burden of skin disease has been poorly explored, and this is a large-scale study to ascertain the association between depression, anxiety, and suicidal ideation with various dermatological diagnoses. This international multicenter observational cross-sectional study was conducted in 13 European countries. In each dermatology clinic, 250 consecutive adult out-patients were recruited to complete a questionnaire, reporting socio-demographic information, negative life events, and suicidal ideation; depression and anxiety were assessed with the Hospital Anxiety and Depression Scale. A clinical examination was performed. A control group was recruited among hospital employees. There were 4,994 participants––3,635 patients and 1,359 controls. Clinical depression was present in 10.1% patients (controls 4.3%, odds ratio (OR) 2.40 (1.67–3.47)). Clinical anxiety was present in 17.2% (controls 11.1%, OR 2.18 (1.68–2.82)). Suicidal ideation was reported by 12.7% of all patients (controls 8.3%, OR 1.94 (1.33–2.82)). For individual diagnoses, only patients with psoriasis had significant association with suicidal ideation. The association with depression and anxiety was highest for patients with psoriasis, atopic dermatitis, hand eczema, and leg ulcers. These results identify a major additional burden of skin disease and have important clinical implications. The contribution of psychological disorders to the burden of skin disease has been poorly explored, and this is a large-scale study to ascertain the association between depression, anxiety, and suicidal ideation with various dermatological diagnoses. This international multicenter observational cross-sectional study was conducted in 13 European countries. In each dermatology clinic, 250 consecutive adult out-patients were recruited to complete a questionnaire, reporting socio-demographic information, negative life events, and suicidal ideation; depression and anxiety were assessed with the Hospital Anxiety and Depression Scale. A clinical examination was performed. A control group was recruited among hospital employees. There were 4,994 participants––3,635 patients and 1,359 controls. Clinical depression was present in 10.1% patients (controls 4.3%, odds ratio (OR) 2.40 (1.67–3.47)). Clinical anxiety was present in 17.2% (controls 11.1%, OR 2.18 (1.68–2.82)). Suicidal ideation was reported by 12.7% of all patients (controls 8.3%, OR 1.94 (1.33–2.82)). For individual diagnoses, only patients with psoriasis had significant association with suicidal ideation. The association with depression and anxiety was highest for patients with psoriasis, atopic dermatitis, hand eczema, and leg ulcers. These results identify a major additional burden of skin disease and have important clinical implications. confidence interval Hospital Anxiety and Depression Scale odds ratio

There is extensive, yet fragmented, evidence of gender differences in academia suggesting that women are underrepresented in most scientific disciplines and publish fewer articles throughout a career, and their work acquires fewer citations. Here, we offer a comprehensive picture of longitudinal gender differences in performance through a bibliometric analysis of academic publishing careers by reconstructing the complete publication history of over 1.5 million gender-identified authors whose publishing career ended between 1955 and 2010, covering 83 countries and 13 disciplines. We find that, paradoxically, the increase of participation of women in science over the past 60 years was accompanied by an increase of gender differences in both productivity and impact. Most surprisingly, though, we uncover two gender invariants, finding that men and women publish at a comparable annual rate and have equivalent career-wise impact for the same size body of work. Finally, we demonstrate that differences in publishing career lengths and dropout rates explain a large portion of the reported career-wise differences in productivity and impact, although productivity differences still remain. This comprehensive picture of gender inequality in academia can help rephrase the conversation around the sustainability of women's careers in academia, with important consequences for institutions and policy makers.

The aims of this study were to (1) determine the activity profiles of a large sample of English FA Premier League soccer players and (2) examine high-intensity running during elite-standard soccer matches for players in various playing positions. Twenty-eight English FA Premier League games were analysed during the 2005-2006 competitive season (n=370), using a multi-camera computerised tracking system. During a typical match, wide midfielders (3138 m, s=565) covered a greater distance in high-intensity running than central midfielders (2825 m, s= 73, P=0.04), full-backs (2605 m, s=387, P < 0.01), attackers (2341 m, s=575, P < 0.01), and central defenders (1834 m, s=256, P < 0.01). In the last 15 min of a game, high-intensity running distance was approximately 20% less than in the first 15-min period for wide midfielders (467 m, s=104 vs. 589 m, s=134, P < 0.01), central midfielders (429 m, s=106 vs. 534 m, s=99, P < 0.01), full-backs (389 m, s=95 vs. 481 m, s=114, P < 0.01), attackers (348 m, s=105 vs. 438 m, s=129, P < 0.01), and central defenders (276 m, s=93 vs. 344 m, s=80, P < 0.01). There was a similar distance deficit for high-intensity running with (148 m, s=78 vs. 193 m, s=96, P < 0.01) and without ball possession (229 m, s=85 vs. 278 m, s=97, P < 0.01) between the last 15-min and first 15-min period of the game. Mean recovery time between very high-intensity running bouts was 72 s (s=28), with a 28% longer recovery time during the last 15 min than the first 15 min of the game (83 s, s=26 vs. 65 s, s=20, P < 0.01). The decline in high-intensity running immediately after the most intense 5-min period was more evident in attackers (216 m, s=50 vs. 113 m, s=47, P < 0.01) and central defenders (182 m, s=26 vs. 96 m, s=39, P < 0.01). The results suggest that high-intensity running with and without ball possession is reduced during various phases of elite-standard soccer matches and the activity profiles and fatigue patterns vary among playing positions. The current findings provide valuable information about the high-intensity running patterns of a large sample of elite-standard soccer players, which could be useful in the development and prescription of specific training regimes.

The largest terrestrial organic carbon pool, carbon in soils, is regulated by an intricate connection between plant carbon inputs, microbial activity, and the soil matrix. This is manifested by how microorganisms, the key players in transforming plant-derived carbon into soil organic carbon, are controlled by the physical arrangement of organic and inorganic soil particles. Here we conduct an incubation of isotopically labelled litter to study effects of soil structure on the fate of litter-derived organic matter. While microbial activity and fungal growth is enhanced in the coarser-textured soil, we show that occlusion of organic matter into aggregates and formation of organo-mineral associations occur concurrently on fresh litter surfaces regardless of soil structure. These two mechanisms-the two most prominent processes contributing to the persistence of organic matter-occur directly at plant-soil interfaces, where surfaces of litter constitute a nucleus in the build-up of soil carbon persistence. We extend the notion of plant litter, i.e., particulate organic matter, from solely an easily available and labile carbon substrate, to a functional component at which persistence of soil carbon is directly determined.

The microbial community of 21 full-scale biogas reactors was examined using 454 pyrosequencing of 16S rRNA gene sequences. These reactors included seven (six mesophilic and one thermophilic) digesting sewage sludge (SS) and 14 (ten mesophilic and four thermophilic) codigesting (CD) various combinations of wastes from slaughterhouses, restaurants, households, etc. The pyrosequencing generated more than 160,000 sequences representing 11 phyla, 23 classes, and 95 genera of Bacteria and Archaea. The bacterial community was always both more abundant and more diverse than the archaeal community. At the phylum level, the foremost populations in the SS reactors included Actinobacteria, Proteobacteria, Chloroflexi, Spirochetes, and Euryarchaeota, while Firmicutes was the most prevalent in the CD reactors. The main bacterial class in all reactors was Clostridia. Acetoclastic methanogens were detected in the SS, but not in the CD reactors. Their absence suggests that methane formation from acetate takes place mainly via syntrophic acetate oxidation in the CD reactors. A principal component analysis of the communities at genus level revealed three clusters: SS reactors, mesophilic CD reactors (including one thermophilic CD and one SS), and thermophilic CD reactors. Thus, the microbial composition was mainly governed by the substrate differences and the process temperature.

Polycomb group (PcG) proteins form multiprotein complexes, called Polycomb repressive complexes (PRCs). PRC2 contains the PcG proteins EZH2, SUZ12, and EED and represses transcription through methylation of lysine (K) 27 of histone H3 (H3). Suz12 is essential for PRC2 activity and its inactivation results in early lethality of mouse embryos. Here, we demonstrate that Suz12(-/-) mouse embryonic stem (ES) cells can be established and expanded in tissue culture. The Suz12(-/-) ES cells are characterized by global loss of H3K27 trimethylation (H3K27me3) and higher expression levels of differentiation-specific genes. Moreover, Suz12(-/-) ES cells are impaired in proper differentiation, resulting in a lack of repression of ES cell markers as well as activation of differentiation-specific genes. Finally, we demonstrate that the PcGs are actively recruited to several genes during ES cell differentiation, which despite an increase in H3K27me3 levels is not always sufficient to prevent transcriptional activation. In summary, we demonstrate that Suz12 is required for the establishment of specific expression programs required for ES cell differentiation. Furthermore, we provide evidence that PcGs have different mechanisms to regulate transcription during cellular differentiation.

Blockchain technology offers a sizable promise to rethink the way interorganizational business processes are managed because of its potential to realize execution without a central party serving as a single point of trust (and failure). To stimulate research on this promise and the limits thereof, in this article, we outline the challenges and opportunities of blockchain for business process management (BPM). We first reflect how blockchains could be used in the context of the established BPM lifecycle and second how they might become relevant beyond. We conclude our discourse with a summary of seven research directions for investigating the application of blockchain technology in the context of BPM.

The focus of this survey is on research in applying evolutionary and other metaheuristic search algorithms to automatically generating content for games, both digital and nondigital (such as board games). The term search-based procedural content generation is proposed as the name for this emerging field, which at present is growing quickly. A taxonomy for procedural content generation is devised, centering on what kind of content is generated, how the content is represented and how the quality/fitness of the content is evaluated; search-based procedural content generation in particular is situated within this taxonomy. This article also contains a survey of all published papers known to the authors in which game content is generated through search or optimisation, and ends with an overview of important open research problems.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

Blockchain technology is often referred to as a groundbreaking innovation and the harbinger of a new economic era. Blockchains may be capable of engendering a new type of economic system: the blockchain economy. In the blockchain economy, agreed-upon transactions would be enforced autonomously, following rules defined by smart contracts. The blockchain economy would manifest itself in a new form of organizational design—decentralized autonomous organizations (DAO)—which are organizations with governance rules specified in the blockchain. We discuss the blockchain economy along dimensions defined in the IT governance literature: decision rights, accountability, and incentives. Our case study of a DAO illustrates that governance in the blockchain economy may depart radically from established notions of governance. Using the three governance dimensions, we propose a novel IT governance framework and a research agenda for governance in the blockchain economy. We challenge common assumptions in the blockchain discourse, and propose promising information systems research related to these assumptions.