A simulation-based multi-criteria management system for optimal water supply under uncertainty

For cost and reliability efficiency, optimal design and operation of pressurized water distribution networks is highly important. However, optimizing such networks is still a challenge since it requires an appropriate determination of: (1) dimension of pipe / pump / tank - decision variables (2) cost / network reliability - objective functions and (3) limits or restrictions within which the network must operate - a given set of constraints. The costs mentioned here consist in general of capital, construction, and operation costs. The reliability of a network mainly refers to the intrinsic capability of providing water with adequate volume and a certain pressure to consumers under normal and extreme conditions. These contradicting objective functions are functions of network configuration regarding component sizes and network layout. Because considerable uncertainties finally render the overall task to a highly complex problem, most recent approaches mainly focus only on finding a trade-off between minimizing cost and maximizing network reliability. To overcome these limitations, a novel model system that simultaneously considers network configuration, its operation and the relevant uncertainties is proposed in this study. For solving this multi-objective design problem, a simulation-based optimization approach has been developed and applied. The approach couples a hydraulic model (Epanet) with the covariance matrix adaptation evolution strategy (CMA-ES) and can be operated in two different modes. These modes are (1) simulation–based Single-objective optimization and (2) simulation-based multi-objective optimization. Single-objective optimization yields the single best solution with respect to cost or network reliability, whereas multi-objective optimization produces a set of non-dominated solutions called Pareto optimal solutions which are trade-offs between cost and reliability. In addition, to prevent a seriously under-designed network, demand uncertainties was also taken into account through a so called “robustness probability” of the network. This consideration may become useful for a more reliable water distribution network. In order to verify the performance of the proposed approach, it was systematically tested on a number of different benchmark water distribution networks ranging from simple to complex. These benchmark networks are either gravity-fed or pumped networks which need to be optimally designed to supply urban or irrigation water demand under specific constraints. The results show that the new approach is able: • to solve optimization problems of pressurized water distribution network design and operation regarding cost and network reliability; • to directly determine the pumping discharge and head, thus allowing to select pumps more adequately; • to simulate time series of tank water level; • to eliminate redundant pipes and pumps to generate an optimal network layout; • to respond well to complex networks other than only to simple networks; • to perform with multiple demand loading; • to produce reliable Pareto optimal solutions regarding multi-objective optimization. In conclusion, the new technique can be successfully applied for optimization problems in pressurized water distribution network design and operation. The new approach has been demonstrated to be a powerful tool for optimal network design not only for irrigation but also for an urban water supply

Meiotic recombination and synapsis in wild-type and asynaptic mutants of tomato (Solanum lycopersicum)

2010 Fall.Includes bibliographical references.Recombination nodules (RNs) and synaptonemal complexes (SCs) are meiosis-specific structures that play important roles in crossing over. During pachytene, RNs mark crossover sites along SCs. MLH1, a mismatch repair protein, promotes crossing over and is a component of most RNs. In wild-type tomato, each bivalent has one, two or three crossovers (=chiasmata), and the number and distribution of these crossovers is affected by crossover interference (the tendency for one crossover to reduce the likelihood of another crossover nearby). Although the phenomenon of genetic interference was discovered nearly one hundred years ago, its molecular basis is still unknown. SCs occur between pairs of homologous chromosomes (bivalents) during prophase I and consist of two parallel rod-like lateral elements held together by transverse fibers. Each lateral element is associated with the two sister chromatids of one of the homologous chromosomes. Cohesin complexes consisting of four proteins (SMC1, SMC3, SYN1/REC8 and SCC3) are found in lateral elements and link sister chromatids together. My research addressed the question of how synapsis (SC formation) is related to the frequency and control of crossing over using tomato, particularly the as1 meiotic mutant, as a model system. Meiocytes from tomato plants homozygous for the mutation as1 do not complete chromosome synapsis and have few chiasmate bivalents, resulting in unbalanced chromosome segregation and sterility. We found a severe delay of prophase I in the as1 mutant compared to wild-type tomato using an in vivo BrdU labeling method, which may be related to the asynaptic phenotype. The asynapsis and delay in the as1 mutant are not likely to be due to a defect in the early steps of recombination, since the frequency and distribution of early recombination proteins (MRE11, RAD50, and RAD51) are similar in wild-type and in the as1 mutant. EM immunolabeling demonstrated that MLH1, a late recombination protein, is present in a subset of RNs in as1, an observation similar to that in wild-type. However, RNs in as1 are larger than those in wild-type. Previous work by other researchers showed a normal level of crossovers in several genetic intervals of the as1 mutant, which was unexpected based on the high degree of asynapsis observed at the cytological level. To evaluate crossing over in the as1 mutant, we examined the immunolabeling patterns of MLH1 foci that mark crossover sites. In as1 meiocytes, we observed that most MLH1 foci were associated with SC segments between two homologous chromosomes. We found that the number of MLH1 foci per micrometer is higher in the as1 mutant compared to wild-type. In addition, interference between MLH1 foci was lower in the mutant than in wild-type tomato. The weakened genetic interference in the as1 mutant may be due to a defect of the medium of interference, since early events of the recombination pathway in as1 seem normal, and MLH1 foci representing crossovers, the last step of the recombination pathway, are still present in the mutant. A good candidate to transmit interference is the cohesin complex that makes up a part of lateral elements. Compared to wild-type, we observed reduced immunofluorescence for the cohesins SMC1, SYN1, and SCC3, but not SMC3 in the as1 mutant. Although we do not yet know the specific mutation of as1 in tomato, we have shown that the asynaptic phenotype is accompanied by alterations in cohesin proteins in AE/LEs and in the distribution of MLH1 foci compared to wild-type. To our knowledge, this is the first report of an association between cohesin proteins and crossover interference regulation in any organism. This discovery represents a significant advance in our efforts to understand the molecular basis of crossover interference

Uniting sex and eukaryote origins in an emerging oxygenic world

<p>Abstract</p> <p>Background</p> <p>Theories about eukaryote origins (eukaryogenesis) need to provide unified explanations for the emergence of diverse complex features that define this lineage. Models that propose a prokaryote-to-eukaryote transition are gridlocked between the opposing "phagocytosis first" and "mitochondria as seed" paradigms, neither of which fully explain the origins of eukaryote cell complexity. Sex (outcrossing with meiosis) is an example of an elaborate trait not yet satisfactorily addressed in theories about eukaryogenesis. The ancestral nature of meiosis and its dependence on eukaryote cell biology suggest that the emergence of sex and eukaryogenesis were simultaneous and synergic and may be explained by a common selective pressure.</p> <p>Presentation of the hypothesis</p> <p>We propose that a local rise in oxygen levels, due to cyanobacterial photosynthesis in ancient Archean microenvironments, was highly toxic to the surrounding biota. This selective pressure drove the transformation of an archaeal (archaebacterial) lineage into the first eukaryotes. Key is that oxygen might have acted in synergy with environmental stresses such as ultraviolet (UV) radiation and/or desiccation that resulted in the accumulation of reactive oxygen species (ROS). The emergence of eukaryote features such as the endomembrane system and acquisition of the mitochondrion are posited as strategies to cope with a metabolic crisis in the cell plasma membrane and the accumulation of ROS, respectively. Selective pressure for efficient repair of ROS/UV-damaged DNA drove the evolution of sex, which required cell-cell fusions, cytoskeleton-mediated chromosome movement, and emergence of the nuclear envelope. Our model implies that evolution of sex and eukaryogenesis were inseparable processes.</p> <p>Testing the hypothesis</p> <p>Several types of data can be used to test our hypothesis. These include paleontological predictions, simulation of ancient oxygenic microenvironments, and cell biological experiments with Archaea exposed to ROS and UV stresses. Studies of archaeal conjugation, prokaryotic DNA recombination, and the universality of nuclear-mediated meiotic activities might corroborate the hypothesis that sex and the nucleus evolved to support DNA repair.</p> <p>Implications of the hypothesis</p> <p>Oxygen tolerance emerges as an important principle to investigate eukaryogenesis. The evolution of eukaryotic complexity might be best understood as a synergic process between key evolutionary innovations, of which meiosis (sex) played a central role.</p> <p>Reviewers</p> <p>This manuscript was reviewed by Eugene V. Koonin, Anthony M. Poole, and Gáspár Jékely.</p

BBP: Brucella genome annotation with literature mining and curation

BACKGROUND: Brucella species are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and animals. Sequences of four Brucella genomes have been published, and various Brucella gene and genome data and analysis resources exist. A web gateway to integrate these resources will greatly facilitate Brucella research. Brucella genome data in current databases is largely derived from computational analysis without experimental validation typically found in peer-reviewed publications. It is partially due to the lack of a literature mining and curation system able to efficiently incorporate the large amount of literature data into genome annotation. It is further hypothesized that literature-based Brucella gene annotation would increase understanding of complicated Brucella pathogenesis mechanisms. RESULTS: The Brucella Bioinformatics Portal (BBP) is developed to integrate existing Brucella genome data and analysis tools with literature mining and curation. The BBP InterBru database and Brucella Genome Browser allow users to search and analyze genes of 4 currently available Brucella genomes and link to more than 20 existing databases and analysis programs. Brucella literature publications in PubMed are extracted and can be searched by a TextPresso-powered natural language processing method, a MeSH browser, a keywords search, and an automatic literature update service. To efficiently annotate Brucella genes using the large amount of literature publications, a literature mining and curation system coined Limix is developed to integrate computational literature mining methods with a PubSearch-powered manual curation and management system. The Limix system is used to quickly find and confirm 107 Brucella gene mutations including 75 genes shown to be essential for Brucella virulence. The 75 genes are further clustered using COG. In addition, 62 Brucella genetic interactions are extracted from literature publications. These results make possible more comprehensive investigation of Brucella pathogenesis. Other BBP features include publication email alert service, Brucella researchers' contact database, and discussion forum. CONCLUSION: BBP is a gateway for Brucella researchers to search, analyze, and curate Brucella genome data originated from public databases and literature. Brucella gene mutations and genetic interactions are annotated using Limix leading to better understanding of Brucella pathogenesis

Comparative genomics of Bacillus thuringiensis phage 0305φ8-36: defining patterns of descent in a novel ancient phage lineage

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Interactomics-Based Functional Analysis: Using Interaction Conservation To Probe Bacterial Protein Functions

The emergence of genomics as a discrete field of biology has changed humanity’s understanding of our relationship with bacteria. Sequencing the genome of each newly-discovered bacterial species can reveal novel gene sequences, though the genome may contain genes coding for hundreds or thousands of proteins of unknown function (PUFs). In some cases, these coding sequences appear to be conserved across nearly all bacteria. Exploring the functional roles of these cases ideally requires an integrative, cross-species approach involving not only gene sequences but knowledge of interactions among their products. Protein interactions, studied at genome scale, extend genomics into the field of interactomics. I have employed novel computational methods to provide context for bacterial PUFs and to leverage the rich genomic, proteomic, and interactomic data available for hundreds of bacterial species. The methods employed in this study began with sets of protein complexes. I initially hypothesized that, if protein interactions reveal protein functions and interactions are frequently conserved through protein complexes, then conserved protein functions should be revealed through the extent of conservation of protein complexes and their components. The subsequent analyses revealed how partial protein complex conservation may, unexpectedly, be the rule rather than the exception. Next, I expanded the analysis by combining sets of thousands of experimental protein-protein interactions. Progressing beyond the scope of protein complexes into interactions across full proteomes revealed novel evolutionary consistencies across bacteria but also exposed deficiencies among interactomics-based approaches. I have concluded this study with an expansion beyond bacterial protein interactions and into those involving bacteriophage-encoded proteins. This work concerns emergent evolutionary properties among bacterial proteins. It is primarily intended to serve as a resource for microbiologists but is relevant to any research into evolutionary biology. As microbiomes and their occupants become increasingly critical to human health, similar approaches may become increasingly necessary

Computational Investigations of Biomolecular Mechanisms in Genomic Replication, Repair and Transcription

High fidelity maintenance of the genome is imperative to ensuring stability and proliferation of cells. The genetic material (DNA) of a cell faces a constant barrage of metabolic and environmental assaults throughout the its lifetime, ultimately leading to DNA damage. Left unchecked, DNA damage can result in genomic instability, inviting a cascade of mutations that initiate cancer and other aging disorders. Thus, a large area of focus has been dedicated to understanding how DNA is damaged, repaired, expressed and replicated. At the heart of these processes lie complex macromolecular dynamics coupled with intricate protein-DNA interactions. Through advanced computational techniques it has become possible to probe these mechanisms at the atomic level, providing a physical basis to describe biomolecular phenomena. To this end, we have performed studies aimed at elucidating the dynamics and interactions intrinsic to the functionality of biomolecules critical to maintaining genomic integrity: modeling the DNA editing mechanism of DNA polymerase III, uncovering the DNA damage recognition/repair mechanism of thymine DNA glycosylase and linking genetic disease to the functional dynamics of the pre-initiation complex transcription machinery. Collectively, our results elucidate the dynamic interplay between proteins and DNA, further broadening our understanding of these complex processes involved with genomic maintenance