On the complexity of hierarchical problem solving

Competent Genetic Algorithms can efficiently address problems in which the linkage between variables is limited to a small order k. Problems with higher order dependencies can only be addressed efficiently if further problem properties exist that can be exploited. An important class of problems for which this occurs is that of hierarchical problems. Hierarchical problems can contain dependencies between all variables (k = n) while being solvable in polynomial time. An open question so far is what precise properties a hierarchical problem must possess in order to be solvable efficiently. We study this question by investigating several features of hierarchical problems and determining their effect on computational complexity, both analytically and empirically. The analyses are based on the Hierarchical Genetic Algorithm (HGA), which is developed as part of this work. The HGA is tested on ranges of hierarchical problems, produced by a generator for hierarchical problems

The Impact of Asynchrony on Parallel Model-Based EAs

In a parallel EA one can strictly adhere to the generational clock, and wait for all evaluations in a generation to be done. However, this idle time limits the throughput of the algorithm and wastes computational resources. Alternatively, an EA can be made asynchronous parallel. However, EAs using classic recombination and selection operators (GAs) are known to suffer from an evaluation time bias, which also influences the performance of the approach. Model-Based Evolutionary Algorithms (MBEAs) are more scalable than classic GAs by virtue of capturing the structure of a problem in a model. If this model is learned through linkage learning based on the population, the learned model may also capture biases. Thus, if an asynchronous parallel MBEA is also affected by an evaluation time bias, this could result in learned models to be less suited to solving the problem, reducing performance. Therefore, in this work, we study the impact and presence of evaluation time biases on MBEAs in an asynchronous parallelization setting, and compare this to the biases in GAs. We find that a modern MBEA, GOMEA, is unaffected by evaluation time biases, while the more classical MBEA, ECGA, is affected, much like GAs are.Comment: 9 pages, 3 figures, 3 tables, submitted to GECCO 202

γ-H2AX foci as in vivo effect biomarker in children emphasize the importance to minimize x-ray doses in paediatric CT imaging

Objectives: Investigation of DNA damage induced by CT x-rays in paediatric patients versus patient dose in a multicentre setting. Methods: From 51 paediatric patients (median age, 3.8 years) who underwent an abdomen or chest CT examination in one of the five participating radiology departments, blood samples were taken before and shortly after the examination. DNA damage was estimated by scoring gamma-H2AX foci in peripheral blood T lymphocytes. Patient-specific organ and tissue doses were calculated with a validated Monte Carlo program. Individual lifetime attributable risks (LAR) for cancer incidence and mortality were estimated according to the BEIR VII risk models. Results: Despite the low CT doses, a median increase of 0.13 gamma-H2AX foci/cell was observed. Plotting the induced gamma-H2AX foci versus blood dose indicated a low-dose hypersensitivity, supported also by an in vitro dose-response study. Differences in dose levels between radiology centres were reflected in differences in DNA damage. LAR of cancer mortality for the paediatric chest CT and abdomen CT cohort was 0.08 and 0.13% respectively. Conclusion: CT x-rays induce DNA damage in paediatric patients even at low doses and the level of DNA damage is reduced by application of more effective CT dose reduction techniques and paediatric protocols

The early diagenetic and PETROphysical behaviour of recent cold-water CARbonate mounds in Deep Environments (PETROCARDE)

Sub-recent cold-water carbonate mounds localized in deeper slope settings on the Atlantic continental margins cannot be any longer neglected in the study of carbonate systems. They clearly play a major role in the dynamics of mixed siliciclastic-carbonate and/or carbonate-dominated continental slopes. Carbonate accumulation rates of cold-water carbonate mounds are about 4 to 12 % of the carbonate accumulation rates of tropical shallow-water reefs but exceed the carbonate accumulation rates of their slope settings by a factor of 4 to 12 (Titschack et al.,2009). These findings emphasize the importance of these carbonate factories as carbonate niches on the continental margins. The primary environmental architecture of such carbonate bodies is well-characterized. However, despite proven evidences of early diagenesis overprinting the primary environmental record (e.g. aragonite dissolution) (Foubert & Henriet, 2009), the extent of early diagenetic and biogeochemical processes shaping the petrophysical nature of mounds is until now not yet fully understood.Understanding (1) the functioning of a carbonate mound as biogeochemical reactor triggering early diagenetic processes and (2) the impact of early diagenesis on the petrophysical behaviour of a carbonate mound in space and through time are necessary (vital) for the reliable prediction of potential late diagenetic processes. Approaching the fossil carbonate mound record, through a profound study of recent carbonate bodies is innovative and will help to better understand processes observed in the fossil mound world (such as cementation, brecciation, fracturing, etc. . . ).In this study, the 155-m high Challenger mound (Porcupine Seabight, SW of Ireland), drilled during IODP Expedition 307 aboard the R/V Joides Resolution (Foubert & Henriet, 2009), and mounds from the Gulf of Cadiz (Moroccan margin) will be discussed in terms of early diagenetic processes and petrophysical behaviour. Early differential diagenesis overprints the primary environmental signals in Challenger mound, with extensive coral dissolution and the genesis of small-scaled semi-lithified layers in the Ca-rich intervals. The low cementation rates compared to the extensive dissolution patterns can be explained by an open-system diagenetic model. Moreover, Pirlet et al. (2009) emphasizes the occurrence of gypsum and dolomite in another mound system (Mound Perseverance) in Porcupine Seabight, which might be also related with fluid oxidation events in a semi-open diagenetic system. Along the Moroccan margins, fluid seepage and fluxes in pore water transport affect the development of mound structures, enhancing extensive cold-water coral dissolution and precipitation of diagenetic minerals such as dolomite, calcite, pyrite, etc. (Foubert et al., 2008). Recent carbonate mounds provide indeed an excellent opportunity to study early diagenetic processes in carbonate systems without the complications of burial and/or later meteoric diagenesis

The R.V. Pelagia pre-drilling site survey at the Rockall and Porcupine cold water coral mounds provinces, European Atlantic margin. The CARBONATE project, ESF EuroMARC program

From 30 September to 22 October 2007 a cruise with the Royal NIOZ research vessel Pelagia was carried out within the framework of the ESF (EuroMARC) project CARBONATE. The goal of this cruise was to complete the existing data set of carbonate mounds present at the European Atlantic margin in order to be able to choose suitable coring sites to drill complete top to base sections through the carbonate mounds with the MeBo drilling device. This is a remotely operated drill that is placed at the sea floor and capable of drilling sediment cores with a maximum length of 85 metres. The drilling cruise, with the Irish research vessel Celtic Explorer, is planned to take place in the summer of 2008.During the Pelagia cruise 5 carbonate mound provinces were visited. The mounds were selected based on two main criteria:the mound provinces should represent different stages in mound developmentit must be possible to penetrate the mounds from top to base with the MeBo (expected maximum sequence thickness in the order of 75 m)The first area that was visited is located at the SE Rockall Bank margin. These mounds are characterised by abundant living cold water corals at their top. The second mound province that was visited is located at the SW Rockall Bank. Initially a large mound cluster known as Franken Mound was chosen for detailed studies. This mound, as well as smaller mounds in the vicinity, is dominated by dead corals and it is considered to be in what is often called the retirement stage. At theWand N margin of the Porcupine Bank two areas were visited. Most of the mounds occur as isolated structures. Only limited amounts of living cold water corals are present. The mounds in the last area that was visited are also referred to as the Magellan Mounds. This is a group of small (<100 m) mounds located in the Porcupine Seabight. These mounds are mostly fully buried and thus represent the final stage of mound development.At all sites a multibeam bathymetric survey was carried out. Subsequently a benthic lander was deployed which was equipped for a period of 2 to 4 days to measure near bed hydrography and sediment transport. This was followed by seismic and video surveys.The initial results of the cruise indicate that at all proposed drilling sites carbonate mounds with a total thickness that can be penetrated by the MeBo are present. The video observations did not reveal the presence of any rough terrain that may hamper the positioning of the MeBo at the seabed

Characterization of the c.190T>C missense mutation in BRCA1 codon 64 (Cys64Arg).

In the Milan area (Northern Italy), we identified a family characterized by a high prevalence of ovarian and breast cancer cases (5 out of 6 subjects, over 3 generations), and a predominant prevalence of ovarian lesions (4 out of 5 patients). Analysis of BRCA1 and BRCA2 genes allowed the identification of the missense c.190T>C mutation in codon 64 (Cys64Arg) of BRCA1. The aims of the present investigation were to characterize the functional implications of the c.190T>C mutation at the molecular level, and to search whether additional polymorphisms might be linked to the peculiar phenotypic features observed in the Italian pedigree. Molecular modelling studies suggested that substitution of the cysteine 64 with an arginine likely disrupts the architecture of the BRCA1 RING finger domain, responsible for the interaction with BARD1, essential for the tumor-suppressor activity of the BRCA1-BARD1 complex. By splicing site information analysis, exonic splicing enhancer site characterization, and analysis of transcript fragment length and sequence, we showed that the c.190T>C mutation was able to modulate the splicing of exon 5 in a fashion opposite to the c.190T>G transversion, responsible for the functionally-related Cys64Gly amino acid substitution. Genotyping of BRCA1 and BRCA2 in the Italian family revealed the presence of two significant polymorphisms: the cancer-associated c.2612C>T SNP in BRCA1, and the c.-26G>A SNP in the BRCA2 gene, acting as an ovarian cancer risk modifier in carriers of deleterious BRCA1 mutations. Analysis of these SNPs in a genotypically-unrelated Polish family, characterized by prevalent breast neoplasms in carriers of the c.190T>C mutation, revealed a genetic profile consistent with the hypothetic role of both polymorphisms

Comparison of established and emerging biodosimetry assays

Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging &gamma;-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the &gamma;-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and &gamma;-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses &ge;1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools

The in vitro remineralizing effect of CPP-ACP and CPP-ACPF after 6 and 12 weeks on initial caries lesion

Objective: The aim of this in vitro study was to determine the effects of remineralization promoting agents containing casein phosphopeptidestabilized amorphous calcium phosphate (CPP-ACP), or CPP-ACP in combination with fluoride (CPP-ACPF) on artificial white spot lesions (WSLs) after 6 and 12 weeks. Methodology: White spot lesions were created on 123 sectioned premolars (246 specimens) with a demineralization solution during a 96 hours pH-cycling regime. Two experimental groups were created: a CPP-ACP group (Tooth MousseTM), and a CPP-ACPF group (Mi Paste PlusTM). Additionally, two control groups were created, one using only a conventional toothpaste (1450 ppm fluoride) and another one without any working agents. All teeth were also daily brushed with the conventional toothpaste except the second control group. Tooth MousseTM and Mi Paste PlusTM were applied for 180 seconds every day. The volume of demineralization was measured with transverse microradiography. Six lesion characteristics regarding the lesion depth and mineral content of WSLs were also determined. Results: The application of CPP-ACP and CPP-ACPF had a significant regenerative effect on the WSLs. Compared to Control group 1 and 2 the volume of demineralization after 6 weeks decreased significantly for CPP-ACP (respectively p&lt;0.001 and p&lt;0.001) and CPP-ACPF (respectively p=0.001 and p=0.003). The same trend was observed after 12 weeks. For the CPP-ACPF group, WSL dimensions decreased significantly between 6 and 12 weeks follow-up (p=0.012). The lesion depth reduced significantly after application of CPP-ACP and CPP-ACPF but increased significantly in the Control groups. Mineral content increased for CPP-ACP and CPP-ACPF after an application period of 12 weeks, but this was only significant for CPP-ACP. Conclusions: Long-term use of CPP-ACP and CPP-ACPF in combination with a conventional tooth paste shows beneficial effects in the recovery of in vitro subsurface caries lesions