Severe head dysgenesis resulting from imbalance between anterior and posterior ontogenetic programs

Head dysgenesis is a major cause of fetal demise and craniofacial malformation. Although mutations in genes of the head ontogenetic program have been reported, many cases remain unexplained. Head dysgenesis has also been related to trisomy or amplification of the chromosomal region overlapping the CDX2 homeobox gene, a master element of the trunk ontogenetic program. Hence, we investigated the repercussion on head morphogenesis of the imbalance between the head and trunk ontogenetic programs, by means of ectopic rostral expression of CDX2 at gastrulation. This caused severe malformations affecting the forebrain and optic structures, and also the frontonasal process associated with defects in neural crest cells colonization. These malformations are the result of the downregulation of genes of the head program together with the abnormal induction of trunk program genes. Together, these data indicate that the imbalance between the anterior and posterior ontogenetic programs in embryos is a new possible cause of head dysgenesis during human development, linked to defects in setting up anterior neuroectodermal structures

Ric-8A, a Gα Protein Guanine Nucleotide Exchange Factor Potentiates Taste Receptor Signaling

Taste receptors for sweet, bitter and umami tastants are G-protein-coupled receptors (GPCRs). While much effort has been devoted to understanding G-protein-receptor interactions and identifying the components of the signalling cascade downstream of these receptors, at the level of the G-protein the modulation of receptor signal transduction remains relatively unexplored. In this regard a taste-specific regulator of G-protein signaling (RGS), RGS21, has recently been identified. To study whether guanine nucleotide exchange factors (GEFs) are involved in the transduction of the signal downstream of the taste GPCRs we investigated the expression of Ric-8A and Ric-8B in mouse taste cells and their interaction with G-protein subunits found in taste buds. Mammalian Ric-8 proteins were initially identified as potent GEFs for a range of Gα subunits and Ric-8B has recently been shown to amplify olfactory signal transduction. We find that both Ric-8A and Ric-8B are expressed in a large portion of taste bud cells and that most of these cells contain IP3R-3 a marker for sweet, umami and bitter taste receptor cells. Ric-8A interacts with Gα-gustducin and Gαi2 through which it amplifies the signal transduction of hTas2R16, a receptor for bitter compounds. Overall, these findings are consistent with a role for Ric-8 in mammalian taste signal transduction

Proteomic Identification of Interleukin-2 Therapy Response in Metastatic Renal Cell Cancer

Introduction—To detect a predictive protein profile that distinguishes between IL-2 therapy responders and non-responders among metastatic RCC patients we used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF-MS). Materials and Methods—Protein extracts of 56 metastatic clear cell RCC patients obtained from radical nephrectomy specimens and prior to IL-2 therapy were applied to protein chip arrays of different chromatographic properties and analyzed using SELDI TOF-MS. A class prediction algorithm was applied to identify a subset of protein peaks whose expression values were associated with IL-2 response status. Multivariate analysis was performed to assess the association between the proteomic profile and the IL-2 response status controlling for the effect of lymphadenopathy. Results—From a total of 513 protein peaks we discovered a predictor set of 11 peaks that performed optimally for predicting IL-2 response status (86 % accuracy, Fisher’s p\u3c0.004, permutation p\u3c0.01). The results were validated on an independent data set with an overall accuracy of 72% (p \u3c 0.05, permutation p\u3c0.01). On multivariate analysis the proteomic profile was significantly associated with IL-2 response when corrected for lymph node status (p\u3c 0.04). Conclusions—We have identified and validated a proteomic pattern that is an independent predictor of IL-2 response. The ability to predict the probability of IL-2 response could permit targeted selection of patients most likely to respond to IL-2, while avoiding unwanted toxicities in patients less likely to respond. This proteomic predictor has the potential to significantly aid clinicians in the decision making of appropriate therapy for metastatic RCC patients

Moho depth and crustal thinning in the Marmara Sea region from gravity data inversion

The free‐air gravity in the Marmara Sea reveals that the low density of sedimentary basins is partly compensated in the lower crust. We compiled geophysical upper crust studies to determine the sediment basin geometries in and around the Marmara Sea and corrected the gravity signal from this upper crust geology with the Parker method. Then, assuming long wavelength anomalies in the residual gravity signal is caused by variations in the Moho topography, we inverted the residual to build the Moho topography. The result shows that the Moho is uplifted on an area greater than the Marmara Sea with a maximum crust thinning beneath the basins where the Moho is at about 25 km, 5 km above the reference depth. We then evaluated the Neogene extension by comparing the surface covered by our 3‐D thinned model with the surface covered by an unthinned model with same crustal volume. Comparing this surface with areal extension rate from GPS data, we found a good compatibility indicating that the extension rate averaged over the Sea of Marmara area probably remained close to its present‐day value during major changes of tectonic regime, as the incursion of the North Anatolian Fault system during the Pliocene leads to the establishment of the dominantly strike‐slip present‐day system. We also show that crustal extension is distributed over a wider domain in the lower crust than in the upper crust, and that this may be accounted for by a relatively minor component of lower crustal ductile flow

Gas and seismicity within the Istanbul seismic gap

Understanding micro-seismicity is a critical question for earthquake hazard assessment. Since the devastating earthquakes of Izmit and Duzce in 1999, the seismicity along the submerged section of North Anatolian Fault within the Sea of Marmara (comprising the “Istanbul seismic gap”) has been extensively studied in order to infer its mechanical behaviour (creeping vs locked). So far, the seismicity has been interpreted only in terms of being tectonic- driven, although the Main Marmara Fault (MMF) is known to strike across multiple hydrocarbon gas sources. Here, we show that a large number of the aftershocks that followed the M 5.1 earthquake of July, 25th 2011 in the western Sea of Marmara, occurred within a zone of gas overpressuring in the 1.5–5 km depth range, from where pressurized gas is expected to migrate along the MMF, up to the surface sediment layers. Hence, gas-related processes should also be considered for a complete interpretation of the micro- seismicity (~M < 3) within the Istanbul offshore domain

Batch-adaptive rejection threshold estimation with application to OCR post-processing

An OCR process is often followed by the application of a language model to find the best transformation of an OCR hypothesis into a string compatible with the constraints of the document, field or item under consideration. The cost of this transformation can be taken as a confidence value and compared to a threshold to decide if a string is accepted as correct or rejected in order to satisfy the need for bounding the error rate of the system. Widespread tools like ROC, precision-recall, or error-reject curves, are commonly used along with fixed thresholding in order to achieve that goal. However, those methodologies fail when a test sample has a confidence distribution that differs from the one of the sample used to train the system, which is a very frequent case in post-processed OCR strings (e.g., string batches showing particularly careful handwriting styles in contrast to free styles). In this paper, we propose an adaptive method for the automatic estimation of the rejection threshold that overcomes this drawback, allowing the operator to define an expected error rate within the set of accepted (non-rejected) strings of a complete batch of documents (as opposed to trying to establish or control the probability of error of a single string), regardless of its confidence distribution. The operator (expert) is assumed to know the error rate that can be acceptable to the user of the resulting data. The proposed system transforms that knowledge into a suitable rejection threshold. The approach is based on the estimation of an expected error vs. transformation cost distribution. First, a model predicting the probability of a cost to arise from an erroneously transcribed string is computed from a sample of supervised OCR hypotheses. Then, given a test sample, a cumulative error vs. cost curve is computed and used to automatically set the appropriate threshold that meets the user-defined error rate on the overall sample. The results of experiments on batches coming from different writing styles show very accurate error rate estimations where fixed thresholding clearly fails. An original procedure to generate distorted strings from a given language is also proposed and tested, which allows the use of the presented method in tasks where no real supervised OCR hypotheses are available to train the system.Navarro Cerdan, JR.; Arlandis Navarro, JF.; Llobet Azpitarte, R.; Perez-Cortes, J. (2015). Batch-adaptive rejection threshold estimation with application to OCR post-processing. Expert Systems with Applications. 42(21):8111-8122. doi:10.1016/j.eswa.2015.06.022S81118122422

North Atlantic Rhodolith Beds

Aggregations of living unattached corallines, previously often referred to as nodules, were given the name rhodoliths by Bosselini and Ginsburg ( 1971 ). Adey and MacIntyre ( 1973 ) provided an early discussion of their genesis and distribution. Such aggregations have long been known as maerl in the North East Atlantic, a Breton term for unattached thalli that lack a shell or pebble core (Irvine and Chamberlain 1994 ). Here, we provide an overview of rhodolith/maerl occurrence in the colder/temperate waters of the North Atlantic and summarize the distribution, species composition, biodiversity and ecological importance of these habitats

Coronal Diagnostics from Narrowband Images around 30.4 nm

Images taken in the band centered at 30.4 nm are routinely used to map the radiance of the He II Ly alpha line on the solar disk. That line is one of the strongest, if not the strongest, line in the EUV observed in the solar spectrum, and one of the few lines in that wavelength range providing information on the upper chromosphere or lower transition region. However, when observing the off-limb corona the contribution from the nearby Si XI 30.3 nm line can become significant. In this work we aim at estimating the relative contribution of those two lines in the solar corona around the minimum of solar activity. We combine measurements from CDS taken in August 2008 with temperature and density profiles from semiempirical models of the corona to compute the radiances of the two lines, and of other representative coronal lines (e.g., Mg X 62.5 nm, Si XII 52.1 nm). Considering both diagnosed quantities from line ratios (temperatures and densities) and line radiances in absolute units, we obtain a good overall match between observations and models. We find that the Si XI line dominates the He II line from just above the limb up to ~2 R_Sun in streamers, while its contribution to narrowband imaging in the 30.4 nm band is expected to become smaller, even negligible in the corona beyond ~2 - 3 R_Sun, the precise value being strongly dependent on the coronal temperature profile.Comment: 26 pages, 11 figures; to be published in: Solar Physic