Glycosylation in Indolent,Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling

The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.     

Hyperparameter estimation for satellite image restoration using a MCMC maximum-likelihood method

The satellite image deconvolution problem is ill-posed and must be regularized. Herein, we use an edge-preserving regularization model using a ? function, involving two hyperparameters. Our goal is to estimate the optimal parameters in order to automatically reconstruct images. We propose to use the maximum-likelihood estimator (MLE), applied to the observed image. We need sampling from prior and posterior distributions. Since the convolution prevents use of standard samplers, we have developed a modified Geman-Yang algorithm, using an auxiliary variable and a cosine transform. We present a Markov chain Monte Carlo maximum-likelihood (MCMCML) technique which is able to simultaneously achieve the estimation and the reconstruction.     

Projection of the sexually dimorphic area of the gerbil hypothalamus to the retrorubral field is essential for male sexual behavior: Role of A8 and other cells.

To determine if the sexually dimorphic area (SDA) of the gerbil hypothalamus affects male sexual behavior through its projections to the retrorubral field (RRF) or ventrolateral periaqueductal gray (PAGvl), these pathways were lesioned asymmetrically. Unilateral radio frequency lesions of the lateral SDA (LSDA), the major source of the pathways, impaired mating when combined with contralateral RRF, but not PAGvl, lesions. N-methyl-{d}-aspartate (NMDA) lesions of the medial SDA, LSDA, and the area between them (the total pathway source) eliminated mating when combined with contralateral, but not ipsilateral, NMDA lesions of the RRF. To determine if A8 cells contributed to these effects, males received NMDA in the SDA and NMDA or 6-hydroxydopamine in the contralateral RRF. When combined with large SDA lesions, A8 lesions impaired but did not eliminate mating. Thus the SDA–RRF pathway, but not an SDA-A8 pathway, is essential for sexual behavior in male gerbils. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Isotherm analyses for single component and multi-component metal sorption onto lignite

The adsorption of the three metal ions, copper, cadmium and zinc in single component and multi-component mixtures in aqueous solutions by lignite is reported. A comparison is made between the single component saturation uptake and the multi-component uptakes. The isotherms indicate a competitive uptake with copper being preferentially absorbed by the lignite in multi-component solutions. The isotherms are plotted to obtain the Langmuir constants, the Freundlich constants and the Redlich–Peterson constants. Lignite is shown to possess an affinity for the metal ions which make its use as an adsorbent a possible alternative to the use of more expensive activated carbons.     

Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1s/sα2s/s Mouse Model of High Affinity for Cardiotonic Steroids

The Na/K-ATPase is the specific receptor for cardiotonic steroids (CTS) such as ouabain and digoxin. At pharmacological concentrations used in the treatment of cardiac conditions, CTS inhibit the ion-pumping function of Na/K-ATPase. At much lower concentrations, in the range of those reported for endogenous CTS in the blood, they stimulate hypertrophic growth of cultured cardiac myocytes through initiation of a Na/K-ATPase-mediated and reactive oxygen species (ROS)-dependent signaling. To examine a possible effect of endogenous concentrations of CTS on cardiac structure and function in vivo, we compared mice expressing the naturally resistant Na/K-ATPase α1 and age-matched mice genetically engineered to express a mutated Na/K-ATPase α1 with high affinity for CTS. In this model, total cardiac Na/K-ATPase activity, α1, α2, and β1 protein content remained unchanged, and the cardiac Na/K-ATPase dose–response curve to ouabain shifted to the left as expected. In males aged 3–6 months, increased α1 sensitivity to CTS resulted in a significant increase in cardiac carbonylated protein content, suggesting that ROS production was elevated. A moderate but significant increase of about 15% of the heart-weight-to-tibia-length ratio accompanied by an increase in the myocyte cross-sectional area was detected. Echocardiographic analyses did not reveal any change in cardiac function, and there was no fibrosis or re-expression of the fetal gene program. RNA sequencing analysis indicated that pathways related to energy metabolism were upregulated, while those related to extracellular matrix organization were downregulated. Consistent with a functional role of the latter, an angiotensin-II challenge that triggered fibrosis in the α1^r/rα2^s/s mouse failed to do so in the α1^s/sα2^s/s. Taken together, these results are indicative of a link between circulating CTS, Na/K-ATPase α1, ROS, and physiological cardiac hypertrophy in mice under baseline laboratory conditions.     

Adaptive output-feedback stabilization of non-local hyperbolic PDEs

We address the problem of adaptive output-feedback stabilization of general first-order hyperbolic partial integro-differential equations (PIDE). Such systems are also referred to as PDEs with non-local (in space) terms. We apply control at one boundary, take measurements on the other boundary, and allow the system’s functional coefficients to be unknown. To deal with the absence of both full-state measurement and parameter knowledge, we introduce a pre-transformation (which happens to be based on backstepping) of the system into an observer canonical form. In that form, the problem of adaptive observer design becomes tractable. Both the parameter estimator and the control law employ only the input and output signals (and their histories over one unit of time). Prior to presenting the adaptive design, we present the non-adaptive/baseline controller, which is novel in its own right and facilitates the understanding of the more complex, adaptive system. The parameter estimator is of the gradient type, based on a parametric model in the form of an integral equation relating delayed values of the input and output. For the closed-loop system we establish boundedness of all signals, pointwise in space and time, and convergence of the PDE state to zero pointwise in space. We illustrate our result with a simulation.     

A framework for dynamic implicit curve approximation by an irregular discrete approach

The approximation of implicit planar curves by line segments is a very classical problem. Many algorithms use interval analysis to approximate this curve, and to handle the topology of the final reconstruction. In this article, we use discrete geometry tools to build an original geometrical and topological representation of the implicit curve. The polygonal approximation contains few segments, and the Reeb graph permits to sum up efficiently the shape and the topology of the curve. Furthermore, we propose two algorithms to process local cells refinement and local cells grouping schemes. We illustrate these schemes with a global system that efficiently handles manual or automatic fast updates on the global reconstruction, by considering topological or geometrical constraints. We also compare the speed and the quality of our approach with two classical methods.     

Enacting language games: the development of a sense of ‘we‐ness’ in online forums

A sense of ‘we‐ness’– enacted through collective identity and culture – is both crucial in online, remote contexts, and particularly difficult to develop in such settings. Using Wittgenstein's concept of language games, we examine how participants of two online forums construct collective identity and culture through their discursive practices. We suggest a strong performative interpretation of the notion of language games, i.e. members of a community produce a sense of we‐ness through their participation in the language game while also defining their expected behaviours and actions. We illustrate how the notion of language games offers an approach for researching and analysing the emergence of collective identity and culture in online forums.     

Automatic computation of pebble roundness using digital imagery and discrete geometry

The shape of sedimentary particles is an important property, from which geographical hypotheses related to abrasion, distance of transport, river behavior, etc. can be formulated. In this paper, we use digital image analysis, especially discrete geometry, to automatically compute some shape parameters such as roundness, i.e. a measure of how much the corners and edges of a particle have been worn away.In contrast to previous work in which traditional digital images analysis techniques, such as Fourier transform, are used, we opted for a discrete geometry approach that allowed us to implement Wadell's original index, which is known to be more accurate, but more time consuming to implement in the field.Our implementation of Wadell's original index is highly correlated (92%) with the roundness classes of Krumbein's chart, used as a ground-truth. In addition, we show that other geometrical parameters, which are easier to compute, can be used to provide good approximations of roundness.We also used our shape parameters to study a set of pebbles digital images taken from the Progo basin river network (Indonesia). The results we obtained are in agreement with previous work and open new possibilities for geomorphologists thanks to automatic computation.