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Background
High blood glucose and diabetes are amongst the conditions causing the greatest losses in years of healthy life worldwide. Therefore, numerous studies aim to identify reliable risk markers for development of impaired glucose metabolism and type 2 diabetes. However, the molecular basis of impaired glucose metabolism is so far insufficiently understood. The development of so called 'omics' approaches in the recent years promises to identify molecular markers and to further understand the molecular basis of impaired glucose metabolism and type 2 diabetes. Although univariate statistical approaches are often applied, we demonstrate here that the application of multivariate statistical approaches is highly recommended to fully capture the complexity of data gained using high-throughput methods.
Methods
We took blood plasma samples from 172 subjects who participated in the prospective Metabolic Syndrome Berlin Potsdam follow-up study (MESY-BEPO Follow-up). We analysed these samples using Gas Chromatography coupled with Mass Spectrometry (GC-MS), and measured 286 metabolites. Furthermore, fasting glucose levels were measured using standard methods at baseline, and after an average of six years. We did correlation analysis and built linear regression models as well as Random Forest regression models to identify metabolites that predict the development of fasting glucose in our cohort.
Results
We found a metabolic pattern consisting of nine metabolites that predicted fasting glucose development with an accuracy of 0.47 in tenfold cross-validation using Random Forest regression. We also showed that adding established risk markers did not improve the model accuracy. However, external validation is eventually desirable. Although not all metabolites belonging to the final pattern are identified yet, the pattern directs attention to amino acid metabolism, energy metabolism and redox homeostasis.
Conclusions
We demonstrate that metabolites identified using a high-throughput method (GC-MS) perform well in predicting the development of fasting plasma glucose over several years. Notably, not single, but a complex pattern of metabolites propels the prediction and therefore reflects the complexity of the underlying molecular mechanisms. This result could only be captured by application of multivariate statistical approaches. Therefore, we highly recommend the usage of statistical methods that seize the complexity of the information given by high-throughput methods.
Agenda gegen Waffenhandel
(2012)
Deutschlands linke Mehrheit ist gespalten. In besonderem Maße betrifft dies außenpolitische Themen. Gegen den menschenfeindlichen Irrsinn von Rüstungsexporten anzugehen könnte hingegen ein einigendes Projekt werden. Die Kanzlerin hat mit ihrer zynischen Behauptung, Rüstungsexporte könnten Bestandteil von Konfliktbearbeitung sein, eine Steilvorlage geboten.
All's well that ends well
(2012)
The transition from cell proliferation to cell expansion is critical for determining leaf size. Andriankaja et al. (2012) demonstrate that in leaves of dicotyledonous plants, a basal proliferation zone is maintained for several days before abruptly disappearing, and that chloroplast differentiation is required to trigger the onset of cell expansion.
Arabische Brüche
(2012)
Können Araber Demokratie? Im Jahr II des Arabischen Frühlings werden erste zarte Triebe der Hoffnungen, die in diese Richtung neigten, von Soldatenstiefeln und flüchtenden Demonstranten zertreten. Die versiegelte Zeit brach auf, doch was ist erreicht worden? In der neuen Ausgabe ziehen wir eine Bilanz, die ebenso sachlich wie zwiespältig ist. Sie zeigt Erfolge, ohne zu beschönigen. Probleme werden sichtbar gemacht, aber auch Wege zu ihrer Lösung. Auch Europa ist gefragt: Wir müssen zu einem neuen, partnerschaftlichen Verhältnis mit den sich wandelnden arabischen Nationen finden!
ASP modulo CSP
(2012)
We present the hybrid ASP solver clingcon, combining the simple modeling language and the high performance Boolean solving capacities of Answer Set Programming (ASP) with techniques for using non-Boolean constraints from the area of Constraint Programming (CP). The new clingcon system features an extended syntax supporting global constraints and optimize statements for constraint variables. The major technical innovation improves the interaction between ASP and CP solver through elaborated learning techniques based on irreducible inconsistent sets. A broad empirical evaluation shows that these techniques yield a performance improvement of an order of magnitude.
Wallfahrten und Pilgerreisen, allgemein der religiös motivierte Tourismus erfreut sich in Europa heute aus unterschiedlichen Motiven wachsender Zustimmung. Die Motivation hierzu wurzelt letztendlich im Bereich der religiösen Emotionalität. Untersucht wird diese Form spiritueller Orientierung in der religiösen Gegenwartskultur auch in seiner Auswirkung auf die religiösen Institutionen. Die Möglichkeit zu religiös motiviertem Reisen kommt dem Bedürfnis nach mehr Religiosität entgegen, ohne daß der Pilgertourist gezwungen ist, sich längerfristig an kirchliche Strukturen binden zu müssen. Der christliche Religionstourismus ist ein bedeutender Globalisierungsfaktor und zahlenmäßig die größte Mobilisierung von Religion.
Für Stefan Zweig war Brasilien 1941 "ein Land der Zukunft". Die Realität sieht anders aus: Bis heute ist es ein Land der Gegensätze, geprägt vor allem durch jenen von Arm und Reich. Was Gini-Koeffizienten nüchtern in Zahlen ausdrücken, kann man in Metropolen mit hypermodernen Zentren und Favelas an Berghängen auf engstem Raum erleben. Vor allem die Verteilung von Land resultiert in Auseinandersetzungen. Experten analysieren im Thema die Lage eines Staates, der in seinen Widersprüchlichkeiten gefangen ist.
The clumping of massive star winds is an established paradigm, which is confirmed by multiple lines of evidence and is supported by stellar wind theory. We use the results from time-dependent hydrodynamical models of the instability in the line-driven wind of a massive supergiant star to derive the time-dependent accretion rate on to a compact object in the Bondi-Hoyle-Lyttleton approximation. The strong density and velocity fluctuations in the wind result in strong variability of the synthetic X-ray light curves. Photoionization of inhomogeneous winds is different from the photoinization of smooth winds. The degree of ionization is affected by the wind clumping. The wind clumping must also be taken into account when comparing the observed and model spectra of the photoionized stellar wind.
The size of plant organs, such as leaves and flowers, is determined by an interaction of genotype and environmental influences. Organ growth occurs through the two successive processes of cell proliferation followed by cell expansion. A number of genes influencing either or both of these processes and thus contributing to the control of final organ size have been identified in the last decade. Although the overall picture of the genetic regulation of organ size remains fragmentary, two transcription factor/microRNA-based genetic pathways are emerging in the control of cell proliferation. However, despite this progress, fundamental questions remain unanswered, such as the problem of how the size of a growing organ could be monitored to determine the appropriate time for terminating growth. While genetic analysis will undoubtedly continue to advance our knowledge about size control in plants, a deeper understanding of this and other basic questions will require including advanced live-imaging and mathematical modeling, as impressively demonstrated by some recent examples. This should ultimately allow the comparison of the mechanisms underlying size control in plants and in animals to extract common principles and lineage-specific solutions.
Weltweit brodelt es, Bürger gehen auf die Straße. In Chile will man sich die Ungerechtigkeiten des Bildungssystems nicht länger gefallen lassen. Nur wer zahlt, darf lernen – dagegen wehrt sich vor allem die Jugend mit aller Macht, auch mit der Macht der Neuen Medien. Öffentlichkeitswirksam werden die Proteste inszeniert. Wird die chilenische Regierung weiterhin mit Knüppeln auf Demonstranten einschlagen oder einlenken?
Wir stehen vor einer Zeitenwende – entweder kommt es zum gemeinsamen Wohlstand oder zum Niedergang Europas in einer immer stärker globalisierten Welt. Deutschland, anteilig mit ca. 20 Prozent die größte und außerordentlich technologiestarke europäische Wirtschaft, trägt dabei eine zentrale politische Verant- wortung. Leider wird die derzeitige schwarz-gelbe Regierung diesen Herausforderungen nicht gerecht. Die seit zwei Jahr- zehnten erfolgreiche Exportoffensive der deutschen Großindustrie, finanziert von Banken, generiert gigantische privatwirtschaftliche Gewinne. Die Reallöhne der Masse der Bevölkerung stagnieren dagegen auf dem Niveau von 1995.
Europa in der Krise – ganz Europa? Deutschland hat von der Krise scheinbar profitiert, buchstäblich: sowohl wirtschaftlich als auch politisch. Die deutsche Führungsrolle für das angeb- lich schwankende Konstrukt der Europäischen Union gilt vielen Kommentatoren als normal. Die wirtschaftliche Kraft des Landes wird als Grundlage seiner hegemonialen Stellung in Europa anerkannt. Die „deutsche Frage“ stellt sich, im Jahr 2012, neu – und ist kritisch zu diskutieren.
Die Entwicklung der nationalen Rohstoffstrategie Deutschlands hat in den vergangenen Jahren deutlich an Struktur, Dynamik und Durchsetzungskraft gewonnen. Einige Vorhaben werden bereits realisiert. Dafür stehen der Aufbau von Rohstoffkooperationen mit Zielländern und die Diskussion über die Definition der strategischen Interessen Deutschlands im Rohstoffbereich.
Much of our knowledge about the solar dynamo is based on sunspot observations. It is thus desirable to extend the set of positional and morphological data of sunspots into the past. Gustav Spörer observed in Germany from Anklam (1861–1873) and Potsdam (1874–1894). He left detailed prints of sunspot groups, which we digitized and processed to mitigate artifacts left in the print by the passage of time. After careful geometrical correction, the sunspot data are now available as synoptic charts for almost 450 solar rotation periods. Individual sunspot positions can thus be precisely determined and spot areas can be accurately measured using morphological image processing techniques. These methods also allow us to determine tilt angles of active regions (Joy’s law) and to assess the complexity of an active region.
The project of public-reason liberalism faces a basic problem: publicly justified principles are typically too abstract and vague to be directly applied to practical political disputes, whereas applicable specifications of these principles are not uniquely publicly justified. One solution could be a legislative procedure that selects one member from the eligible set of inconclusively justified proposals. Yet if liberal principles are too vague to select sufficiently specific legislative proposals, can they, nevertheless, select specific legislative procedures? Based on the work of Gerald Gaus, this article argues that the only candidate for a conclusively justified decision procedure is a majoritarian or otherwise ‘neutral’ democracy. If the justification of democracy requires an equality baseline in the design of political regimes and if justifications for departure from this baseline are subject to reasonable disagreement, a majoritarian design is justified by default. Gaus’s own preference for super-majoritarian procedures is based on disputable specifications of justified liberal principles. These procedures can only be defended as a sectarian preference if the equality baseline is rejected, but then it is not clear how the set of justifiable political regimes can be restricted to full democracies.
Dynamic regulatory on/off minimization for biological systems under internal temporal perturbations
(2012)
Background: Flux balance analysis (FBA) together with its extension, dynamic FBA, have proven instrumental for analyzing the robustness and dynamics of metabolic networks by employing only the stoichiometry of the included reactions coupled with adequately chosen objective function. In addition, under the assumption of minimization of metabolic adjustment, dynamic FBA has recently been employed to analyze the transition between metabolic states.
Results: Here, we propose a suite of novel methods for analyzing the dynamics of (internally perturbed) metabolic networks and for quantifying their robustness with limited knowledge of kinetic parameters. Following the biochemically meaningful premise that metabolite concentrations exhibit smooth temporal changes, the proposed methods rely on minimizing the significant fluctuations of metabolic profiles to predict the time-resolved metabolic state, characterized by both fluxes and concentrations. By conducting a comparative analysis with a kinetic model of the Calvin-Benson cycle and a model of plant carbohydrate metabolism, we demonstrate that the principle of regulatory on/off minimization coupled with dynamic FBA can accurately predict the changes in metabolic states.
Conclusions: Our methods outperform the existing dynamic FBA-based modeling alternatives, and could help in revealing the mechanisms for maintaining robustness of dynamic processes in metabolic networks over time.
Early acquisition of a second language influences the development of language abilities and cognitive functions. In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the impact of early bilingualism on the organization of the cortical language network during sentence production. Two groups of adult multilinguals, proficient in three languages, were tested on a narrative task; early multilinguals acquired the second language before the age of three years, late multilinguals after the age of nine. All participants learned a third language after nine years of age. Comparison of the two groups revealed substantial differences in language-related brain activity for early as well as late acquired languages. Most importantly, early multilinguals preferentially activated a fronto-striatal network in the left hemisphere, whereas the left posterior superior temporal gyrus (pSTG) was activated to a lesser degree than in late multilinguals. The same brain regions were highlighted in previous studies when a non-target language had to be controlled. Hence the engagement of language control in adult early multilinguals appears to be influenced by the specific learning and acquisition conditions during early childhood. Remarkably, our results reveal that the functional control of early and subsequently later acquired languages is similarly affected, suggesting that language experience has a pervasive influence into adulthood. As such, our findings extend the current understanding of control functions in multilinguals.
Ernährung garantiert?
(2012)
Alle Menschen haben elementare Gemeinsamkeiten: Um zu überleben, müssen sie atmen, trinken – und essen. Doch ist Ernährung garantiert? Der Diskurs über globale Ernährungssicherung führte Jahrzehnte lang ein Schattendasein. Nun erfährt die Agrarwirtschaft eine Renaissance, doch ob dies den Hungernden zugutekommen wird, ist fraglich: Immer mehr Produkte sollen nicht den Energiebedarf der Menschen, sondern den der Maschinen decken. In unserem aktuellen Thema diskutieren Experten die Möglichkeiten und Risiken dieser veränderten Wertschätzung der Landwirtschaft.
Europa ohne Kompass
(2012)
Die noch nicht ausgestandene Staatsschuldenkrise seit Ende 2009 hat Europa stärker verändert, als viele wahrhaben wollen. Es stellt sich die grundsätzliche Frage des Sinns der europäischen Integration. Vor allem die Glaubwürdigkeit des europäischen politischen Führungspersonals hat gelitten. Ohne Kompass wurstelt man sich seit mehr als zwei Jahren durch. Keine "rote Linie", die nicht nach wenigen Wochen überschritten wurde, kein Masterplan, der nicht bald Makulatur geworden ist.
F2C2
(2012)
Background: Flux coupling analysis (FCA) has become a useful tool in the constraint-based analysis of genome-scale metabolic networks. FCA allows detecting dependencies between reaction fluxes of metabolic networks at steady-state. On the one hand, this can help in the curation of reconstructed metabolic networks by verifying whether the coupling between reactions is in agreement with the experimental findings. On the other hand, FCA can aid in defining intervention strategies to knock out target reactions.
Results: We present a new method F2C2 for FCA, which is orders of magnitude faster than previous approaches. As a consequence, FCA of genome-scale metabolic networks can now be performed in a routine manner.
Conclusions: We propose F2C2 as a fast tool for the computation of flux coupling in genome-scale metabolic networks. F2C2 is freely available for non-commercial use at https://sourceforge.net/projects/f2c2/files/.