The potential of an observational data set for calibration of a computationally expensive computer model

PublishedJournal ArticleWe measure the potential of an observational data set to constrain a set of inputs to a complex and computationally expensive computer model. We use each member in turn of an ensemble of output from a computationally expensive model, corresponding to an observable part of a modelled system, as a proxy for an observational data set. We argue that, given some assumptions, our ability to constrain uncertain parameter inputs to a model using its own output as data, provides a maximum bound for our ability to constrain the model inputs using observations of the real system. The ensemble provides a set of known parameter input and model output pairs, which we use to build a computationally effic. © 2013 Author(s).This work was supported by funding from the ice2sea programme from the European Union 7th Framework Programme, grant number 226375. Ice2sea contribution number 154

Cardiovascular magnetic resonance in patients with pectus excavatum compared with normal controls

<p>Abstract</p> <p>Purpose</p> <p>To assess cardiothoracic structure and function in patients with pectus excavatum compared with control subjects using cardiovascular magnetic resonance imaging (CMR).</p> <p>Method</p> <p>Thirty patients with pectus excavatum deformity (23 men, 7 women, age range: 14-67 years) underwent CMR using 1.5-Tesla scanner (Siemens) and were compared to 25 healthy controls (18 men, 7 women, age range 18-50 years). The CMR protocol included cardiac cine images, pulmonary artery flow quantification, time resolved 3D contrast enhanced MR angiography (CEMRA) and high spatial resolution CEMRA. Chest wall indices including maximum transverse diameter, pectus index (PI), and chest-flatness were measured in all subjects. Left and right ventricular ejection fractions (LVEF, RVEF), ventricular long and short dimensions (LD, SD), mid-ventricle myocardial shortening, pulmonary-systemic circulation time, and pulmonary artery flow were quantified.</p> <p>Results</p> <p>In patients with pectus excavatum, the pectus index was 9.3 ± 5.0 versus 2.8 ± 0.4 in controls (P < 0.001). No significant differences between pectus excavatum patients and controls were found in LV ejection fraction, LV myocardial shortening, pulmonary-systemic circulation time or pulmonary flow indices. In pectus excavatum, resting RV ejection fraction was reduced (53.9 ± 9.6 versus 60.5 ± 9.5; P = 0.013), RVSD was reduced (P < 0.05) both at end diastole and systole, RVLD was increased at end diastole (P < 0.05) reflecting geometric distortion of the RV due to sternal compression.</p> <p>Conclusion</p> <p>Depression of the sternum in pectus excavatum patients distorts RV geometry. Resting RVEF was reduced by 6% of the control value, suggesting that these geometrical changes may influence myocardial performance. Resting LV function, pulmonary circulation times and pulmonary vascular anatomy and perfusion indices were no different to controls.</p

A 100%-complete sequence reveals unusually simple genomic features in the hot-spring red alga Cyanidioschyzon merolae

<p>Abstract</p> <p>Background</p> <p>All previously reported eukaryotic nuclear genome sequences have been incomplete, especially in highly repeated units and chromosomal ends. Because repetitive DNA is important for many aspects of biology, complete chromosomal structures are fundamental for understanding eukaryotic cells. Our earlier, nearly complete genome sequence of the hot-spring red alga <it>Cyanidioschyzon merolae </it>revealed several unique features, including just three ribosomal DNA copies, very few introns, and a small total number of genes. However, because the exact structures of certain functionally important repeated elements remained ambiguous, that sequence was not complete. Obviously, those ambiguities needed to be resolved before the unique features of the <it>C. merolae </it>genome could be summarized, and the ambiguities could only be resolved by completing the sequence. Therefore, we aimed to complete all previous gaps and sequence all remaining chromosomal ends, and now report the first nuclear-genome sequence for any eukaryote that is 100% complete.</p> <p>Results</p> <p>Our present complete sequence consists of 16546747 nucleotides covering 100% of the 20 linear chromosomes from telomere to telomere, representing the simple and unique chromosomal structures of the eukaryotic cell. We have unambiguously established that the <it>C. merolae </it>genome contains the smallest known histone-gene cluster, a unique telomeric repeat for all chromosomal ends, and an extremely low number of transposons.</p> <p>Conclusion</p> <p>By virtue of these attributes and others that we had discovered previously, <it>C. merolae </it>appears to have the simplest nuclear genome of the non-symbiotic eukaryotes. These unusually simple genomic features in the 100% complete genome sequence of <it>C. merolae </it>are extremely useful for further studies of eukaryotic cells.</p

Complete Sequencing and Pan-Genomic Analysis of Lactobacillus delbrueckii subsp. bulgaricus Reveal Its Genetic Basis for Industrial Yogurt Production

Lactobacillus delbrueckii subsp. bulgaricus (Lb. bulgaricus) is an important species of Lactic Acid Bacteria (LAB) used for cheese and yogurt fermentation. The genome of Lb. bulgaricus 2038, an industrial strain mainly used for yogurt production, was completely sequenced and compared against the other two ATCC collection strains of the same subspecies. Specific physiological properties of strain 2038, such as lysine biosynthesis, formate production, aspartate-related carbon-skeleton intermediate metabolism, unique EPS synthesis and efficient DNA restriction/modification systems, are all different from those of the collection strains that might benefit the industrial production of yogurt. Other common features shared by Lb. bulgaricus strains, such as efficient protocooperation with Streptococcus thermophilus and lactate production as well as well-equipped stress tolerance mechanisms may account for it being selected originally for yogurt fermentation industry. Multiple lines of evidence suggested that Lb. bulgaricus 2038 was genetically closer to the common ancestor of the subspecies than the other two sequenced collection strains, probably due to a strict industrial maintenance process for strain 2038 that might have halted its genome decay and sustained a gene network suitable for large scale yogurt production

Widespread Over-Expression of the X Chromosome in Sterile F1 Hybrid Mice

The X chromosome often plays a central role in hybrid male sterility between species, but it is unclear if this reflects underlying regulatory incompatibilities. Here we combine phenotypic data with genome-wide expression data to directly associate aberrant expression patterns with hybrid male sterility between two species of mice. We used a reciprocal cross in which F1 males are sterile in one direction and fertile in the other direction, allowing us to associate expression differences with sterility rather than with other hybrid phenotypes. We found evidence of extensive over-expression of the X chromosome during spermatogenesis in sterile but not in fertile F1 hybrid males. Over-expression was most pronounced in genes that are normally expressed after meiosis, consistent with an X chromosome-wide disruption of expression during the later stages of spermatogenesis. This pattern was not a simple consequence of faster evolutionary divergence on the X chromosome, because X-linked expression was highly conserved between the two species. Thus, transcriptional regulation of the X chromosome during spermatogenesis appears particularly sensitive to evolutionary divergence between species. Overall, these data provide evidence for an underlying regulatory basis to reproductive isolation in house mice and underscore the importance of transcriptional regulation of the X chromosome to the evolution of hybrid male sterility

Cholera- and Anthrax-Like Toxins Are among Several New ADP-Ribosyltransferases

Chelt, a cholera-like toxin from Vibrio cholerae, and Certhrax, an anthrax-like toxin from Bacillus cereus, are among six new bacterial protein toxins we identified and characterized using in silico and cell-based techniques. We also uncovered medically relevant toxins from Mycobacterium avium and Enterococcus faecalis. We found agriculturally relevant toxins in Photorhabdus luminescens and Vibrio splendidus. These toxins belong to the ADP-ribosyltransferase family that has conserved structure despite low sequence identity. Therefore, our search for new toxins combined fold recognition with rules for filtering sequences – including a primary sequence pattern – to reduce reliance on sequence identity and identify toxins using structure. We used computers to build models and analyzed each new toxin to understand features including: structure, secretion, cell entry, activation, NAD+ substrate binding, intracellular target binding and the reaction mechanism. We confirmed activity using a yeast growth test. In this era where an expanding protein structure library complements abundant protein sequence data – and we need high-throughput validation – our approach provides insight into the newest toxin ADP-ribosyltransferases

Value Chain Integration – A Framework for Assessment

Despite an abundance of research on the topic, firms continue to struggle with integrating their value chains in order to create and deliver more value to customers. Silo-thinking (rather than systems-thinking) is a typical symptom of poorly integrated value chains. In this paper, we explore the enablers of better value chain integration, before developing and presenting a framework that can be used for assessing the maturity of value chain integration in organizations. We draw on practical insights from a multiple case study of several diverse companies currently working with the systematic integration of their value chains