Oracle-based optimization applied to climate model calibration

In this paper, we show how oracle-based optimization can be effectively used for the calibration of an intermediate complexity climate model. In a fully developed example, we estimate the 12 principal parameters of the C-GOLDSTEIN climate model by using an oracle- based optimization tool, Proximal-ACCPM. The oracle is a procedure that finds, for each query point, a value for the goodness-of-fit function and an evaluation of its gradient. The difficulty in the model calibration problem stems from the need to undertake costly calculations for each simulation and also from the fact that the error function used to assess the goodness-of-fit is not convex. The method converges to a Fbest fit_ estimate over 10 times faster than a comparable test using the ensemble Kalman filter. The approach is simple to implement and potentially useful in calibrating computationally demanding models based on temporal integration (simulation), for which functional derivative information is not readily available

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

The relationship between the presence of neighbours and rates of sexual and asexual reproduction in a colonial invertebrate

The colonial ascidian Didemnum moseleyi (Herdman) is apparently the kind of organism that should conform to the so-called "Strawberry-Coral model", which predicts that the ratio of sexual to asexual reproduction in organisms like strawberries and corals is greater in crowded than open conditions. It is a thin, white, subtidal colonial ascidian dwelling beneath kelp forests in the shallow coastal waters of New South Wales, Australia. Colonies regularly undergo fission and fusion; the resultant effect is a population of ramets each up to 15 mm diameter. Individuals brood their embryos until a fairly late stage. Rates of sexual and asexual reproduction were examined here for colonies of D. moseleyi that were crowded by a sponge or by conspecific ascidians. Rates of sexual and asexual reproduction were smaller close to sponges, suggesting that exudates from sponges may have had toxic effects on D. moseleyi. Where the natural death of sponges provided free space for D. moseleyi, this was often not colonized, suggesting that, despite appearances, sponges and D. moseleyi were not in immediate competition for space. Rates of fission and production of embryos were also recorded for D. moseleyi ramets at different densities. Again, contrary to expectation, the ratio of sexual to asexual reproduction was larger in colonies at small densities. It was concluded that experimental tests are required to determine causal relationships between crowding and rates of reproduction

The effect of solar activity on the Doppler and multipath spread of HF signals received over paths oriented along the mid-latitude trough

Measurements of the Doppler and delay spread associated with HF signals propagating along an oblique (1440 km) path tangential to the midlatitude ionospheric trough are presented for sunspot maximum and minimum. During the day, Doppler spread is independent of solar activity, but for winter and equinoctial nights, it is very much higher at sunspot maximum. The delay spread is also generally higher at sunspot maximum for all seasons and times of day. For sunspot minimum, measurements from a second, longer path (1800 km) are also presented. The observed Doppler and delay spreads are similar for both paths. Finally, a novel method of more accurately deriving the delay spread defined by the International Telecommunication Union (i.e., the largest delay spread including all modes that have a peak power within a user-defined threshold of that of the strongest mode) from Voice of America coverage analysis program (VOACAP) predictions is presented. For the first time, the predicted values are compared with the measured delay spreads and, while there is generally good agreement at sunspot minimum, the agreement at sunspot maximum tends to be poor because the behavior of the high-order ionospheric modes (e.g., 3F2) is not well predicted by VOACAP