Functional Metagenomic Investigations of the Human Intestinal Microbiota

The human intestinal microbiota encode multiple critical functions impacting human health, including metabolism of dietary substrate, prevention of pathogen invasion, immune system modulation, and provision of a reservoir of antibiotic resistance genes accessible to pathogens. The complexity of this microbial community, its recalcitrance to standard cultivation, and the immense diversity of its encoded genes has necessitated the development of novel molecular, microbiological, and genomic tools. Functional metagenomics is one such culture-independent technique, used for decades to study environmental microorganisms, but relatively recently applied to the study of the human commensal microbiota. Metagenomic functional screens characterize the functional capacity of a microbial community, independent of identity to known genes, by subjecting the metagenome to functional assays in a genetically tractable host. Here we highlight recent work applying this technique to study the functional diversity of the intestinal microbiota, and discuss how an approach combining high-throughput sequencing, cultivation, and metagenomic functional screens can improve our understanding of interactions between this complex community and its human host

Research on stress and smoking: progress and problems

Despite evidence that smoking behaviour increases in the context of stress, there has yet to be a clear-cut demonstration that nicotine intake is similarly enhanced. Although nicotine intake has been shown to reduce reported anxiety in the context of stress, the controlling conditions (type of stressor, intensity, temporal relationships, etc.) need further exploration. Recent findings involving nicotine's effects on the hypophyseal-adrenal axis provide a new perspective on these issues, in that increased nicotine intake during exposure to a stressor may represent, at least in part, behavioral compensation for diminished sensitivity to nicotine brought about by nicotine-stimulated corticosteroid release. Corticosteroids may decrease central nervous system excitability in a way that could account for anxiety reduction; on the other hand, anxiety reduction may be an epiphenomenon with respect to the reinforcement of smoking behaviour. The integration of behavioural, physiological, and biochemical research exemplified by the above approach should lead to a better understanding of stress and smoking.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73317/1/j.1360-0443.1991.tb01815.x.pd

Simulating Serial-Target Antibacterial Drug Synergies Using Flux Balance Analysis

Flux balance analysis (FBA) is an increasingly useful approach for modeling the behavior of metabolic systems. However, standard FBA modeling of genetic knockouts cannot predict drug combination synergies observed between serial metabolic targets, even though such synergies give rise to some of the most widely used antibiotic treatments. Here we extend FBA modeling to simulate responses to chemical inhibitors at varying concentrations, by diverting enzymatic flux to a waste reaction. This flux diversion yields very similar qualitative predictions to prior methods for single target activity. However, we find very different predictions for combinations, where flux diversion, which mimics the kinetics of competitive metabolic inhibitors, can explain serial target synergies between metabolic enzyme inhibitors that we confirmed in Escherichia coli cultures. FBA flux diversion opens the possibility for more accurate genome-scale predictions of drug synergies, which can be used to suggest treatments for infections and other diseases

On the Dialectics of Global Governance in the Twenty-first Century : A Polanyian Double Movement?

Following decades of economic globalisation and market-oriented reforms across the world, Karl Polanyi’s double movement has been invoked not only to explain what is happening but also to give reasons for being hopeful about a different future. Some have suggested a pendulum model of history: a swing from markets to society leading, in the next phase, to a swing from society to markets, and so on. The double movement can also be understood dialectically as a description of an irreversible historical development following its own inner laws or schemes of development. Going beyond a thesis – antithesis – synthesis pattern, I maintain that conceptions and schemes drawn from dialectics, and especially dialectical critical realism, can provide better geo-historical hypotheses for explaining past changes and for building scenarios about possible future changes. I analyse political economy contradictions and tendencies, and focus on normative rationality, to assess substantial claims about rational tendential directionality of world history. I argue that democratic global Keynesianism would enable processes of decommodification and new syntheses concerning the market/social nexus. A learning process towards qualitatively higher levels of reflexivity can help develop global transformative agency. Existing contradictions can be resolved by means of rational collective actions and building more adequate common institutions. These collective actions are likely to involve new forms of political agency such as world political parties.Peer reviewe

A modality-adaptive method for segmenting brain tumors and organs-at-risk in radiation therapy planning

In this paper we present a method for simultaneously segmenting brain tumors and an extensive set of organs-at-risk for radiation therapy planning of glioblastomas. The method combines a contrast-adaptive generative model for whole-brain segmentation with a new spatial regularization model of tumor shape using convolutional restricted Boltzmann machines. We demonstrate experimentally that the method is able to adapt to image acquisitions that differ substantially from any available training data, ensuring its applicability across treatment sites; that its tumor segmentation accuracy is comparable to that of the current state of the art; and that it captures most organs-at-risk sufficiently well for radiation therapy planning purposes. The proposed method may be a valuable step towards automating the delineation of brain tumors and organs-at-risk in glioblastoma patients undergoing radiation therapy

Adaptation to climate change in Finland : Current state and future prospects

The KOKOSOPU project has aimed at a comprehensive evaluation of the national adaptation policy with particular emphasis on the National Adaptation Plan and international policy development. In addition, future challenges related to societal development have been taken into account. Projections of climate change, Finland’s Climate Act and the strengthened adaptation policy in the EU emphasise the importance of the national adaptation policy. A key objective of the National Adaptation Plan 2014–2022 was to strengthen the adaptive capacity of Finnish society. This objective is still relevant. The conditions for reaching the objective have, however, partly changed. First, cross border consequences of climate change are increasingly emphasised. Second, issues of justice and fairness with respect to the consequences of climate change and adaptation actions are being identified as central. Third, greater weight is given to the overall sustainability of adaptation and climate action. The changing conditions for climate change adaptation should be reflected in the allocation of resources, in improved coordination within the administration and in co-operation between the public and private sector. In addition, knowledge and education should be enhanced, and resources provided for RDI, and for monitoring and evaluation that supports continued improvement of adaptation activities

Adaptation to climate change in Finland : Current state and future prospects

The KOKOSOPU project has aimed at a comprehensive evaluation of the national adaptation policy with particular emphasis on the National Adaptation Plan and international policy development. In addition, future challenges related to societal development have been taken into account. Projections of climate change, Finland’s Climate Act and the strengthened adaptation policy in the EU emphasise the importance of the national adaptation policy. A key objective of the National Adaptation Plan 2014–2022 was to strengthen the adaptive capacity of Finnish society. This objective is still relevant. The conditions for reaching the objective have, however, partly changed. First, cross border consequences of climate change are increasingly emphasised. Second, issues of justice and fairness with respect to the consequences of climate change and adaptation actions are being identified as central. Third, greater weight is given to the overall sustainability of adaptation and climate action. The changing conditions for climate change adaptation should be reflected in the allocation of resources, in improved coordination within the administration and in co-operation between the public and private sector. In addition, knowledge and education should be enhanced, and resources provided for RDI, and for monitoring and evaluation that supports continued improvement of adaptation activities

Comparing nuclear power trajectories in Germany and the UK: from ‘regimes' to ‘democracies’ in sociotechnical transitions and Discontinuities

This paper focuses on arguably the single most striking contrast in contemporary major energy politics in Europe (and even the developed world as a whole): the starkly differing civil nuclear policies of Germany and the UK. Germany is seeking entirely to phase out nuclear power by 2022. Yet the UK advocates a ‘nuclear renaissance’, promoting the most ambitious new nuclear construction programme in Western Europe.Here,this paper poses a simple yet quite fundamental question: what are the particular divergent conditions most strongly implicated in the contrasting developments in these two countries. With nuclear playing such an iconic role in historical discussions over technological continuity and transformation, answering this may assist in wider understandings of sociotechnical incumbency and discontinuity in the burgeoning field of‘sustainability transitions’. To this end, an ‘abductive’ approach is taken: deploying nine potentially relevant criteria for understanding the different directions pursued in Germany and the UK. Together constituted by 30 parameters spanning literatures related to socio-technical regimes in general as well as nuclear technology in particular, the criteria are divided into those that are ‘internal’ and ‘external’ to the ‘focal regime configuration’ of nuclear power and associated ‘challenger technologies’ like renewables. It is ‘internal’ criteria that are emphasised in conventional sociotechnical regime theory, with ‘external’ criteria relatively less well explored. Asking under each criterion whether attempted discontinuation of nuclear power would be more likely in Germany or the UK, a clear picture emerges. ‘Internal’ criteria suggest attempted nuclear discontinuation should be more likely in the UK than in Germany– the reverse of what is occurring. ‘External’ criteria are more aligned with observed dynamics –especially those relating to military nuclear commitments and broader ‘qualities of democracy’. Despite many differences of framing concerning exactly what constitutes ‘democracy’, a rich political science literature on this point is unanimous in characterising Germany more positively than the UK. Although based only on a single case,a potentially important question is nonetheless raised as to whether sociotechnical regime theory might usefully give greater attention to the general importance of various aspects of democracy in constituting conditions for significant technological discontinuities and transformations. If so, the policy implications are significant. A number of important areas are identified for future research, including the roles of diverse understandings and specific aspects of democracy and the particular relevance of military nuclear commitments– whose under-discussion in civil nuclear policy literatures raises its own questions of democratic accountability