Local Behavior of Sparse Analysis Regularization: Applications to Risk Estimation

In this paper, we aim at recovering an unknown signal x0 from noisy L1measurements y=Phi*x0+w, where Phi is an ill-conditioned or singular linear operator and w accounts for some noise. To regularize such an ill-posed inverse problem, we impose an analysis sparsity prior. More precisely, the recovery is cast as a convex optimization program where the objective is the sum of a quadratic data fidelity term and a regularization term formed of the L1-norm of the correlations between the sought after signal and atoms in a given (generally overcomplete) dictionary. The L1-sparsity analysis prior is weighted by a regularization parameter lambda>0. In this paper, we prove that any minimizers of this problem is a piecewise-affine function of the observations y and the regularization parameter lambda. As a byproduct, we exploit these properties to get an objectively guided choice of lambda. In particular, we develop an extension of the Generalized Stein Unbiased Risk Estimator (GSURE) and show that it is an unbiased and reliable estimator of an appropriately defined risk. The latter encompasses special cases such as the prediction risk, the projection risk and the estimation risk. We apply these risk estimators to the special case of L1-sparsity analysis regularization. We also discuss implementation issues and propose fast algorithms to solve the L1 analysis minimization problem and to compute the associated GSURE. We finally illustrate the applicability of our framework to parameter(s) selection on several imaging problems

POSYDON: A General-Purpose Population Synthesis Code with Detailed Binary-Evolution Simulations

Most massive stars are members of a binary or a higher-order stellar systems, where the presence of a binary companion can decisively alter their evolution via binary interactions. Interacting binaries are also important astrophysical laboratories for the study of compact objects. Binary population synthesis studies have been used extensively over the last two decades to interpret observations of compact-object binaries and to decipher the physical processes that lead to their formation. Here, we present POSYDON, a novel, binary population synthesis code that incorporates full stellar-structure and binary-evolution modeling, using the MESA code, throughout the whole evolution of the binaries. The use of POSYDON enables the self-consistent treatment of physical processes in stellar and binary evolution, including: realistic mass-transfer calculations and assessment of stability, internal angular-momentum transport and tides, stellar core sizes, mass-transfer rates and orbital periods. This paper describes the detailed methodology and implementation of POSYDON, including the assumed physics of stellar- and binary-evolution, the extensive grids of detailed single- and binary-star models, the post-processing, classification and interpolation methods we developed for use with the grids, and the treatment of evolutionary phases that are not based on pre-calculated grids. The first version of POSYDON targets binaries with massive primary stars (potential progenitors of neutron stars or black holes) at solar metallicity.Comment: 60 pages, 33 figures, 8 tables, referee's comments addressed. The code and the accompanying documentations and data products are available at https:\\posydon.or

Safety and Effectiveness of Central Venous Catheterization in Patients with Cancer: Prospective Observational Study

This study investigated the safety and effectiveness of each type of central venous catheters (CVC) in patients with cancer. We prospectively enrolled patients with cancer who underwent catherization involving a subclavian venous catheter (SVC), peripherally inserted central venous catheter (PICC), or chemo-port (CP) in our department. From March 2007 to March 2009, 116 patients underwent 179 episodes of catherization. A SVC was inserted most frequently (46.4%). Fifty-four complications occurred (30.1%): infection in 23 cases, malpositioning or migration of the tip in 18 cases, thrombosis in eight cases, and bleeding in five cases. Malpositioning or migration of the tip occurred more frequently with a PICC (P<0.001); infection occurred more often with a tunneled catheter (P=0.028) and was observed more often in young patients (P=0.023). The catheter life span was longer for patients with solid cancer (P=0.002) than for those with hematologic cancer, with a CP (P<0.001) than a PICC or SVC, and for an indwelling catheter with image guidance (P=0.014) than a blind procedure. In conclusion, CP is an effective tool for long term use and the fixation of tip is important for the management of PICC

Footprints of Inversions at Present and Past Pseudoautosomal Boundaries in Human Sex Chromosomes

The human sex chromosomes have stopped recombining gradually, which has left five evolutionary strata on the X chromosome. Y inversions are thought to have suppressed X–Y recombination but clear evidence is missing. Here, we looked for such evidence by focusing on a region—the X-added region (XAR)—that includes the pseudoautosomal region and the most recent strata 3 to 5. We estimated and analyzed the whole set of parsimonious scenarios of Y inversions given the gene order in XAR and its Y homolog. Comparing these to scenarios for simulated sequences suggests that the strata 4 and 5 were formed by Y inversions. By comparing the X and Y DNA sequences, we found clear evidence of two Y inversions associated with duplications that coincide with the boundaries of strata 4 and 5. Divergence between duplicates is in agreement with the timing of strata 4 and 5 formation. These duplicates show a complex pattern of gene conversion that resembles the pattern previously found for AMELXY, a stratum 3 locus. This suggests that this locus—despite AMELY being unbroken—was possibly involved in a Y inversion that formed stratum 3. However, no clear evidence supporting the formation of stratum 3 by a Y inversion was found, probably because this stratum is too old for such an inversion to be detectable. Our results strongly support the view that the most recent human strata have arisen by Y inversions and suggest that inversions have played a major role in the differentiation of our sex chromosomes

Genipin cross-linked chitosan for signal enhancement in the colorimetric detection of aflatoxin B1 on 3MM chromatography paper

Detection of mycotoxins by conventional methods such as ELISA or LC-MS can be expensive and time-consuming. Therefore, paper-based biosensors can be effectively used for on-site analysis, due to their low cost and easy detection procedures. Nevertheless, even when the application of colorimetric methods on paper enhance the simplicity and affordability of multiple determinations, the signal intensity and final readout can be affected by a limited color uniformity. In this work, Ellman’s method for the quantification of aflatoxin B1 was utilized as a model colorimetric assay on paper, in which the test zones were modified with chitosan-immobilized enzyme (AChE). A comparison of the cross-linking effect of genipin on two chitosans of varying molar mass and degree of acetylation, exhibited a greater signal enhancement from the sample with a higher degree of acetylation and molecular weight

MalDA, Accelerating Malaria Drug Discovery

© 2021 The Authors The Malaria Drug Accelerator (MalDA) is a consortium of 15 leading scientific laboratories. The aim of MalDA is to improve and accelerate the early antimalarial drug discovery process by identifying new, essential, druggable targets. In addition, it seeks to produce early lead inhibitors that may be advanced into drug candidates suitable for preclinical development and subsequent clinical testing in humans. By sharing resources, including expertise, knowledge, materials, and reagents, the consortium strives to eliminate the structural barriers often encountered in the drug discovery process. Here we discuss the mission of the consortium and its scientific achievements, including the identification of new chemically and biologically validated targets, as well as future scientific directions

Low Pathogenic Avian Influenza Isolates from Wild Birds Replicate and Transmit via Contact in Ferrets without Prior Adaptation

Direct transmission of avian influenza viruses to mammals has become an increasingly investigated topic during the past decade; however, isolates that have been primarily investigated are typically ones originating from human or poultry outbreaks. Currently there is minimal comparative information on the behavior of the innumerable viruses that exist in the natural wild bird host. We have previously demonstrated the capacity of numerous North American avian influenza viruses isolated from wild birds to infect and induce lesions in the respiratory tract of mice. In this study, two isolates from shorebirds that were previously examined in mice (H1N9 and H6N1 subtypes) are further examined through experimental inoculations in the ferret with analysis of viral shedding, histopathology, and antigen localization via immunohistochemistry to elucidate pathogenicity and transmission of these viruses. Using sequence analysis and glycan binding analysis, we show that these avian viruses have the typical avian influenza binding pattern, with affinity for cell glycoproteins/glycolipids having terminal sialic acid (SA) residues with α 2,3 linkage [Neu5Ac(α2,3)Gal]. Despite the lack of α2,6 linked SA binding, these AIVs productively infected both the upper and lower respiratory tract of ferrets, resulting in nasal viral shedding and pulmonary lesions with minimal morbidity. Moreover, we show that one of the viruses is able to transmit to ferrets via direct contact, despite its binding affinity for α 2,3 linked SA residues. These results demonstrate that avian influenza viruses, which are endemic in aquatic birds, can potentially infect humans and other mammals without adaptation. Finally this work highlights the need for additional study of the wild bird subset of influenza viruses in regard to surveillance, transmission, and potential for reassortment, as they have zoonotic potential