Data-matched filter

After amplification and normalization, incoming data bits are fed, alternately, to pair of integrators. While one integrator is operating, content of other is on hold, sample, and dump. Clock derived in bit-timing extractor times and controls integrators. Frequency of clock is one-half data rate

Some Problems in Probabilistic Tomography

Given probability distributions F1 , F2 , . . ., Fk on R and distinct directions θ1, . . ., θk, one may ask whether there is a probability measure μ on R2 such that the marginal of μ in direction θj is Fj, j = 1, . . ., k. For example for k = 3 we ask what the marginal of μ at 45° can be if the x and y marginals are each say standard normal? In probabilistic language, if X and Y are each standard normal with an arbitrary joint distribution, what can the distribution of X + Y or X - Y be? This type of question is familiar to probabilists and is also familiar (except perhaps in that μ is positive) to tomographers, but is difficult to answer in special cases. The set of distributions for Z = X - Y is a convex and compact set, C, which contains the single point mass Z ≡ 0 since X ≡ Y, standard normal, is possible. We show that Z can be 3-valued, Z=0, ±a for any a, each with positive probability, but Z cannot have any (genuine) two-point distribution. Using numerical linear programming we present convincing evidence that Z can be uniform on the interval [-ε, ε] for ε small and give estimates for the largest such ε. The set of all extreme points of C seems impossible to determine explicitly. We also consider the more basic question of finding the extreme measures on the unit square with uniform marginals on both coordinates, and show that not every such measure has a support which has only one point on each horizontal or vertical line, which seems surprising

GMRF Estimation under Topological and Spectral Constraints

International audienceWe investigate the problem of Gaussian Markov random field selection under a non-analytic constraint: the estimated models must be compatible with a fast inference algorithm, namely the Gaussian belief propagation algorithm. To address this question, we introduce the *-IPS framework, based on iterative proportional scaling, which incrementally selects candidate links in a greedy manner. Besides its intrinsic sparsity-inducing ability, this algorithm is flexible enough to incorporate various spectral constraints, like e.g. walk summability, and topological constraints, like short loops avoidance. Experimental tests on various datasets, including traffic data from San Francisco Bay Area, indicate that this approach can deliver, with reasonable computational cost, a broad range of efficient inference models, which are not accessible through penalization with traditional sparsity-inducing norms

Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization

Tumors build vessels by cooption of pre-existing vasculature and de novo recruitment of bone marrow (BM)-derived endothelial progenitor cells (EPCs). However, the contribution and the functional role of EPCs in tumor neoangiogenesis are controversial. Therefore, by using genetically marked BM progenitor cells, we demonstrate the precise spatial and temporal contribution of EPCs to the neovascularization of three transplanted and one spontaneous breast tumor in vivo using high-resolution microscopy and flow cytometry. We show that early tumors recruit BM-derived EPCs that differentiate into mature BM-derived endothelial cells (ECs) and luminally incorporate into a subset of sprouting tumor neovessels. Notably, in later tumors, these BM-derived vessels are diluted with non-BM-derived vessels from the periphery, which accounts for purported differences in previously published reports. Furthermore, we show that specific ablation of BM-derived EPCs with alpha-particle-emitting anti-VE-cadherin antibody markedly impaired tumor growth associated with reduced vascularization. Our results demonstrate that BM-derived EPCs are critical components of the earliest phases of tumor neoangiogenesis

Aerosolized amikacin for treatment of pulmonary Mycobacterium avium infections: an observational case series

BACKGROUND: Current systemic therapy for nontuberculous mycobacterial pulmonary infection is limited by poor clinical response rates, drug toxicities and side effects. The addition of aerosolized amikacin to standard oral therapy for nontuberculous mycobacterial pulmonary infection may improve treatment efficacy without producing systemic toxicity. This study was undertaken to assess the safety, tolerability and preliminary clinical benefits of the addition of aerosolized amikacin to a standard macrolide-based oral treatment regimen. CASE PRESENTATIONS: Six HIV-negative patients with Mycobacterium avium intracellulare pulmonary infections who had failed standard therapy were administered aerosolized amikacin at 15 mg/kg daily in addition to standard multi-drug macrolide-based oral therapy. Patients were monitored clinically and serial sputum cultures were obtained to assess response to therapy. Symptomatic improvement with radiographic stabilization and eradication of mycobacterium from sputum were considered markers of success. Of the six patients treated with daily aerosolized amikacin, five responded to therapy. All of the responders achieved symptomatic improvement and four were sputum culture negative after 6 months of therapy. Two patients became re-infected with Mycobacterium avium intracellulare after 7 and 21 months of treatment. One of the responders who was initially diagnosed with Mycobacterium avium intracellulare became sputum culture positive for Mycobacterium chelonae resistant to amikacin after being on intermittent therapy for 4 years. One patient had progressive respiratory failure and died despite additional therapy. There was no evidence of nephrotoxicity or ototoxicity associated with therapy. CONCLUSION: Aerosolized delivery of amikacin is a promising adjunct to standard therapy for pulmonary nontuberculous mycobacterial infections. Larger prospective trials are needed to define its optimal role in therapy of this disease

PET Imaging of Soluble Yttrium-86-Labeled Carbon Nanotubes in Mice

The potential medical applications of nanomaterials are shaping the landscape of the nanobiotechnology field and driving it forward. A key factor in determining the suitability of these nanomaterials must be how they interface with biological systems. Single walled carbon nanotubes (CNT) are being investigated as platforms for the delivery of biological, radiological, and chemical payloads to target tissues. CNT are mechanically robust graphene cylinders comprised of sp(2)-bonded carbon atoms and possessing highly regular structures with defined periodicity. CNT exhibit unique mechanochemical properties that can be exploited for the development of novel drug delivery platforms. In order to evaluate the potential usefulness of this CNT scaffold, we undertook an imaging study to determine the tissue biodistribution and pharmacokinetics of prototypical DOTA-functionalized CNT labeled with yttrium-86 and indium-111 ((86)Y-CNT and (111)In-CNT, respectively) in a mouse model.The (86)Y-CNT construct was synthesized from amine-functionalized, water-soluble CNT by covalently attaching multiple copies of DOTA chelates and then radiolabeling with the positron-emitting metal-ion, yttrium-86. A gamma-emitting (111)In-CNT construct was similarly prepared and purified. The constructs were characterized spectroscopically, microscopically, and chromatographically. The whole-body distribution and clearance of yttrium-86 was characterized at 3 and 24 hours post-injection using positron emission tomography (PET). The yttrium-86 cleared the blood within 3 hours and distributed predominantly to the kidneys, liver, spleen and bone. Although the activity that accumulated in the kidney cleared with time, the whole-body clearance was slow. Differential uptake in these target tissues was observed following intravenous or intraperitoneal injection.The whole-body PET images indicated that the major sites of accumulation of activity resulting from the administration of (86)Y-CNT were the kidney, liver, spleen, and to a much less extent the bone. Blood clearance was rapid and could be beneficial in the use of short-lived radionuclides in diagnostic applications

Modulation of Plasma Lipidomic Profiles in Metastatic Castration-Resistant Prostate Cancer by Simvastatin

Elevated circulating sphingolipids are associated with shorter overall survival and therapeutic resistance in metastatic castration-resistant prostate cancer (mCRPC), suggesting that perturbations in sphingolipid metabolism promotes prostate cancer growth. This study assessed whether addition of simvastatin to standard treatment for mCRPC can modify a poor prognostic circulating lipidomic profile represented by a validated 3-lipid signature (3LS). Men with mCRPC (n = 27) who were not on a lipid-lowering agent, were given simvastatin for 12 weeks (40 mg orally, once daily) with commencement of standard treatment. Lipidomic profiling was performed on their plasma sampled at baseline and after 12 weeks of treatment. Only 11 men had the poor prognostic 3LS at baseline, of whom five (45%) did not retain the 3LS after simvastatin treatment (expected conversion rate with standard treatment = 19%). At baseline, the plasma profiles of men with the 3LS displayed higher levels (p < 0.05) of sphingolipids (ceramides, hexosylceramides and sphingomyelins) than those of men without the 3LS. These plasma sphingolipids were reduced after statin treatment in men who lost the 3LS (mean decrease: 23–52%, p < 0.05), but not in men with persistent 3LS, and were independent of changes to plasma cholesterol, LDL-C or triacylglycerol. In conclusion, simvastatin in addition to standard treatment can modify the poor prognostic circulating lipidomic profile in mCRPC into a more favourable profile at twice the expected conversion rate.Blossom Mak, Hui-Ming Lin, Thy Duong, Kate L. Mahon, Anthony M. Joshua, Martin R. Stockler, Howard Gurney, Francis Parnis, Alison Zhang, Tahlia Scheinberg, Gary Wittert, Lisa M. Butler, David Sullivan, Andrew J. Hoy, Peter J. Meikle, and Lisa G. Horvat