A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking

Insights gained from multilevel computational models of biological systems can be translated into real-life applications only if the model correctness has been verified first. One of the most frequently employed in silico techniques for computational model verification is model checking. Traditional model checking approaches only consider the evolution of numeric values, such as concentrations, over time and are appropriate for computational models of small scale systems (e.g. intracellular networks). However for gaining a systems level understanding of how biological organisms function it is essential to consider more complex large scale biological systems (e.g. organs). Verifying computational models of such systems requires capturing both how numeric values and properties of (emergent) spatial structures (e.g. area of multicellular population) change over time and across multiple levels of organization, which are not considered by existing model checking approaches. To address this limitation we have developed a novel approximate probabilistic multiscale spatio-temporal meta model checking methodology for verifying multilevel computational models relative to specifications describing the desired/expected system behaviour. The methodology is generic and supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to generate it. In addition, the methodology can be automatically adapted to case study specific types of spatial structures and properties using the spatio-temporal meta model checking concept. To automate the computational model verification process we have implemented the model checking approach in the software tool Mule (http://mule.modelchecking.org). Its applicability is illustrated against four systems biology computational models previously published in the literature encoding the rat cardiovascular system dynamics, the uterine contractions of labour, the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. Our methodology and software will enable computational biologists to efficiently develop reliable multilevel computational models of biological systems

Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to resistance; and strengthen the case for a role in survival of systems involved in manganese and iron homeostasis

Undergraduate political attitudes: An examination of peer, faculty, and social influences

A socialization perspective is used to examine the processes through which undergraduate student political attitudes are influenced by peers, faculty, and social trends. Using the model of undergraduate socialization provided by Weidman (1989) as a framework, I examine how the normative contexts of college campuses and students' interactions with peers and faculty serve to influence the political orientations of students, net of precollege and college characteristics. Based on longitudinal data from the Cooperative Institutional Research Program, the results indicate that student orientations change in ways quite similar to trends observed more generally, and that peer and faculty normative contexts tend to have a positive influence of equal magnitude on political orientations of students.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43617/1/11162_2005_Article_BF01724937.pd

Is Happiness a trait?

ABSTRACT One of the ideological foundations of the modern welfare states is the belief that people can be made happier by providing them with better living conditions. This belief is challenged by the theory that happiness is a fixed 'trait', rather than a variable 'state'. This theory figures both at the individual level and at the societal level. The individual level variant depicts happiness as an aspect of personal character; rooted in inborn temperament or acquired disposition. The societal variant sees happiness as a matter of national character; embedded in shared values and beliefs. Both variants imply that a better society makes no happier people. Happiness can be regarded as a trait if it meets three criteria: 1) temporal stability, 2) cross-situational consistency, and 3) inner causation. This paper checks whether that is, indeed, the case. The theory that happiness is a personal-character-trait is tested in a (meta) analysis of longitudinal studies. The results are: 1) Happiness is quite stable on the short term, but not in the long run, neither relatively nor absoloutely. 2) Happiness is not insensitive to fortune or adversity. 3) Happiness is not entirely built-in: its genetic basis is at best modest and psychological factors explain only part of its variance. The theory that happiness is a national-character-trait is tested in an analysis of differences in average happiness between nations. The results point in the same direction: 1) Though generally fairly stable over the last decades, nation-happiness has changed profoundly in some cases both absolutely and relatively. 2) Average happiness in nations is clearly not indep