MOLECULAR AND GENOMIC BASED INSIGHTS INTO THE EVOLUTION OF ENTEROCOCCUS FAECIUM FROM COMMENSAL TO HOSPITAL-ADAPTED PATHOGEN

The basis for the recent transition of Enterococcus faecium from a primarily commensal organism to one of the leading causes of hospital-acquired infections in the United States is not yet understood. To address this, the first part of my project assessed isolates from early outbreaks in the USA and South America using sequence analysis, colony hybridizations, and minimal inhibitory concentrations (MICs) which showed clinical isolates possess virulence and antibiotic resistance determinants that are less abundant or lacking in community isolates. I also revealed that the level of ampicillin resistance increased over time in clinical strains. By sequencing the pbp5 gene, I demonstrated an ~5% difference in the pbp5 gene between strains with MICs <4ug/ml and those with MICs >4µg/ml, but no specific sequence changes correlated with increases in MICs within the latter group. A 3-10% nucleotide difference was also seen in three other genes analyzed, which suggested the existence of two distinct subpopulations of E. faecium. This led to the second part of my project analyzing concatenated core gene sequences, SNPs, the 16S rRNA, and phylogenetics of 21 E. faecium genomes confirming two distinct clades; a community-associated (CA) clade and hospital-associated (HA) clade. Molecular clock calculations indicate that these two clades likely diverged ~ 300,000 to > 1 million years ago, long before the modern antibiotic era. Genomic analysis also showed that, in addition to core genomic differences, HA E. faecium harbor specific accessory genetic elements that may confer selection advantages over CA E. faecium. The third part of my project discovered 6 E. faecium genes with the newly identified “WxL” domain. My analyses, using RT-PCR, western blots, patient sera, whole-cell ELISA, and immunogold electron microscopy, indicated that E. faecium WxL genes exist in operons, encode bacterial cell surface localized proteins, that WxL proteins are antigenic in humans, and are more exposed on the surface of clinical isolates versus community isolates (even though they are ubiquitous in both clades). ELISAs and BIAcore analyses also showed that proteins encoded by these operons bind several different host extracellular matrix proteins, as well as to each other, suggesting a novel cell-surface complex. In summary, my studies provide new insights into the evolution of E. faecium by showing that there are two distantly related clades; one being more successful in the hospital setting. My studies also identified operons encoding WxL proteins whose characteristics could also contribute to colonization and virulence within this species.

The evolution of high-temperature mylonitic microfabrics: evidence from simple shearing of a quartz analogue (norcamphor)

Plane strain simple shearing of norcamphor (C7H10O) in a see-through deformation rig to a shear strain of γ = 10.5 at a homologous temperature of Th = 0.81 yields a microfabric similar to that of quartz in amphibolite facies mylonite. Synkinematic analysis of the norcamphor microfabric reveals that the development of a steady-state texture is linked to changes in the relative activities of several grain-scale mechanisms. Three stages of textural and microstructural evolution are distinguished: (1) rotation and shearing of the intracrystalline glide planes are accommodated by localized deformation along three sets of anastomozing microshears. A symmetrical c-axis girdle reflects localized pure shear extension along the main microshear set (Sa) oblique to the bulk shear zone boundary (abbreviated as SZB); (2) progressive rotation of the microshears into parallelism with the SZB increases the component of simple shear on the Sa microshears. Grain-boundary migration recrystallization favours the survival of grains with slip systems oriented for easy glide. This is associated with a textural transition towards two stable c-axis point maxima whose skeletal outline is oblique with respect to the Sa microshears and the SZB; and (3) at high shear strains (γ > 8), the microstructure, texture and mechanism assemblage are strain invariant, but strain continues to partition into rotating sets of microshears. Steady state is therefore a dynamic, heterogeneous condition involving the cyclic nucleation, growth and consumption of grains.

Transport Development and the Evolution of Economic Geography

In this paper, based on the recent advances in the new economic geography (e.g., Fujita, Krugman and Venables [12]), we analyze impacts of transport costs on the spatial patterns of economic agglomeration. We first identify prototypes from the existing models, and explain the mechanism of how transport costs influence the balance between economic forces of agglomeration and dispersion. We then investigate the transformation of the agglomeration/dispersion patterns given gradually decreasing transport costs for different goods.

On the Evolution of the Spatial Economy with Multi-unit/Multi-plant Firms: The Impact of IT Development

This paper examines how the decline of communication costs between management and production facilities within firms and the decrease in trade costs of manufactured goods affect the spatial organization of a two-region economy with multi-unit/multi-plant firms. The development of information technology decreases the costs of communication and trade costs. Thus, the fragmentation of firms is promoted. Our result indicates that, with decreasing communication costs, firms producing low trade-cost products (such as consumer electronics) tend to concentrate their manufacturing plants in low wage countries. In contrast, firms producing high trade-cost products (such as automobiles) tend to have multiple plants serving to segmented markets, even in the absence of wage differentials.

Globalization and the Evolution of the Supply Chain: who gains and who loses?

This paper focuses on two distinct facets of globalization: the decrease in the trade costs of goods and the decline of communication costs between headquarters and production facilities within firms. When the unskilled have about the same wage in the two regions, the decrease of these costs fosters the gradual agglomeration of plants in the core region accommodating the headquarters. By contrast, when the wage gap is significant, the process of integration eventually triggers the re-location of plants into the periphery. In particular, when the process of re-location is driven by falling communication costs, the welfare of all workers living in the core goes down whereas the welfare of those who reside in the periphery rises.

The Evolution of the "One China" Concept in the Process of Taiwan's Democratization

This paper investigates how Taiwan's "one China" concept evolved during the democratization process that occurred under the leadership of former President Lee Teng-hui. The author argues that there was a crucial evolution of the "one China" concept and that the transformation of the concept resulted from changes in Taiwan's internal political circumstances. The evolution of the concept creates a real possibility that the "status quo" sought by the ROC in the Taiwan Strait both during and after the Cold War might be destroyed. In addition, any further evolution of the "one China" concept will surely make the "status quo" of Taiwan untenable, in that it would induce Taiwan to seek de jure instead of de facto independence, possibly initiating a conflict between the PRC and the ROC. To prevent such a conflict in the Taiwan Strait, the international community must persuade the ROC not to go beyond the "status quo" and to stay within the framework of de facto independence. At the same time, both the PRC and the ROC should be urged to maintain an open conduit of communication for productive talks on the reunification of China.

Modification and Developer Metrics at the Function Level: Metrics for the Study of the Evolution of a Software Project

Software evolution, and particularly its growth, has been mainly studied at the file (also sometimes referred as module) level. In this paper we propose to move from the physical towards a level that includes semantic information by using functions or methods for measuring the evolution of a software system. We point out that use of functions-based metrics has many advantages over the use of files or lines of code. We demonstrate our approach with an empirical study of two Free/Open Source projects: a community-driven project, Apache, and a company-led project, Novell Evolution. We discovered that most functions never change; when they do their number of modifications is correlated with their size, and that very few authors who modify each; finally we show that the departure of a developer from a software project slows the evolution of the functions that she authored.

Numerical simulation of the evolution of viscous rotating drops

In this contribution we simulate numerically the evolution of a viscous fluid drop rotating about a fixed axis at constant angular velocity ? or constant angular momentum L, surrounded by another viscous fluid. The problem is considered in the limit of large Ekman number and small Reynolds number. In the lecture we will describe the numerical method we have used to solve the PDE system that describes the evolution of the drop (3D boundary element method). We will also present the results we have obtained, paying special attention to the stability/instability of the equilibrium shapes.

Study of the evolution of the seismic cycle of stress and strain associated to the El Salvador Fault Zone

• Central America: – Regional studies in Central America (Seismic Hazard). – El Salvador Fault Zone (ESFZ). – Aguacaliente‐Navarro Fault Zone (ANFZ), Central Valley of Costa Rica. – Haiti (seismic hazard) • Spain: – Regional‐Nacional studies of seismic hazards (applications to building codes, eurocode, emergency plans, etc.) – Betic range zone, south of Spain. – Ibero‐Maghrebi region (collision zone)

The evolution of the brain, the human nature of cortical circuits and intellectual creativity

The tremendous expansion and the differentiation of the neocortex constitute two major events in the evolution of the mammalian brain. The increase in size and complexity of our brains opened the way to a spectacular development of cognitive and mental skills. This expansion during evolution facilitated the addition of microcircuits with a similar basic structure, which increased the complexity of the human brain and contributed to its uniqueness. However, fundamental differences even exist between distinct mammalian species. Here, we shall discuss the issue of our humanity from a neurobiological and historical perspective.

Intensive Metrics for the Study of the Evolution of Open Source Projects: Case Studies from Apache Software Foundation Projects

Based on the empirical evidence that the ratio of email messages in public mailing lists to versioning system commits has remained relatively constant along the history of the Apache Software Foundation (ASF), this paper has as goal to study what can be inferred from such a metric for projects of the ASF. We have found that the metric seems to be an intensive metric as it is independent of the size of the project, its activity, or the number of developers, and remains relatively independent of the technology or functional area of the project. Our analysis provides evidence that the metric is related to the technical effervescence and popularity of project, and as such can be a good candidate to measure its healthy evolution. Other, similar metrics -like the ratio of developer messages to commits and the ratio of issue tracker messages to commits- are studied for several projects as well, in order to see if they have similar characteristics.

Modeling the evolution of item rating networks using time-domain preferential attachment

The understanding of the structure and dynamics of the intricate network of connections among people that consumes products through Internet appears as an extremely useful asset in order to study emergent properties related to social behavior. This knowledge could be useful, for example, to improve the performance of personal recommendation algorithms. In this contribution, we analyzed five-year records of movie-rating transactions provided by Netflix, a movie rental platform where users rate movies from an online catalog. This dataset can be studied as a bipartite user-item network whose structure evolves in time. Even though several topological properties from subsets of this bipartite network have been reported with a model that combines random and preferential attachment mechanisms [Beguerisse Díaz et al., 2010], there are still many aspects worth to be explored, as they are connected to relevant phenomena underlying the evolution of the network. In this work, we test the hypothesis that bursty human behavior is essential in order to describe how a bipartite user-item network evolves in time. To that end, we propose a novel model that combines, for user nodes, a network growth prescription based on a preferential attachment mechanism acting not only in the topological domain (i.e. based on node degrees) but also in time domain. In the case of items, the model mixes degree preferential attachment and random selection. With these ingredients, the model is not only able to reproduce the asymptotic degree distribution, but also shows an excellent agreement with the Netflix data in several time-dependent topological properties.

The evolution of the laws of software evolution. A discussion based on a systematic literature review

After more than 40 years of life, software evolution should be considered as a mature field. However, despite such a long history, many research questions still remain open, and controversial studies about the validity of the laws of software evolution are common. During the first part of these 40 years the laws themselves evolved to adapt to changes in both the research and the software industry environments. This process of adaption to new paradigms, standards, and practices stopped about 15 years ago, when the laws were revised for the last time. However, most controversial studies have been raised during this latter period. Based on a systematic and comprehensive literature review, in this paper we describe how and when the laws, and the software evolution field, evolved. We also address the current state of affairs about the validity of the laws, how they are perceived by the research community, and the developments and challenges that are likely to occur in the coming years.