Uncertainty in multitask learning: joint representations for probabilistic MR-only radiotherapy planning

Multi-task neural network architectures provide a mechanism that jointly integrates information from distinct sources. It is ideal in the context of MR-only radiotherapy planning as it can jointly regress a synthetic CT (synCT) scan and segment organs-at-risk (OAR) from MRI. We propose a probabilistic multi-task network that estimates: 1) intrinsic uncertainty through a heteroscedastic noise model for spatially-adaptive task loss weighting and 2) parameter uncertainty through approximate Bayesian inference. This allows sampling of multiple segmentations and synCTs that share their network representation. We test our model on prostate cancer scans and show that it produces more accurate and consistent synCTs with a better estimation in the variance of the errors, state of the art results in OAR segmentation and a methodology for quality assurance in radiotherapy treatment planning.Comment: Early-accept at MICCAI 2018, 8 pages, 4 figure

Contractile force is enhanced in Aortas from pendrin null mice due to stimulation of angiotensin II-dependent signaling.

Pendrin is a Cl-/HCO3- exchanger expressed in the apical regions of renal intercalated cells. Following pendrin gene ablation, blood pressure falls, in part, from reduced renal NaCl absorption. We asked if pendrin is expressed in vascular tissue and if the lower blood pressure observed in pendrin null mice is accompanied by reduced vascular reactivity. Thus, the contractile responses to KCl and phenylephrine (PE) were examined in isometrically mounted thoracic aortas from wild-type and pendrin null mice. Although pendrin expression was not detected in the aorta, pendrin gene ablation changed contractile protein abundance and increased the maximal contractile response to PE when normalized to cross sectional area (CSA). However, the contractile sensitivity to this agent was unchanged. The increase in contractile force/cross sectional area observed in pendrin null mice was due to reduced cross sectional area of the aorta and not from increased contractile force per vessel. The pendrin-dependent increase in maximal contractile response was endothelium- and nitric oxide-independent and did not occur from changes in Ca2+ sensitivity or chronic changes in catecholamine production. However, application of 100 nM angiotensin II increased force/CSA more in aortas from pendrin null than from wild type mice. Moreover, angiotensin type 1 receptor inhibitor (candesartan) treatment in vivo eliminated the pendrin-dependent changes contractile protein abundance and changes in the contractile force/cross sectional area in response to PE. In conclusion, pendrin gene ablation increases aorta contractile force per cross sectional area in response to angiotensin II and PE due to stimulation of angiotensin type 1 receptor-dependent signaling. The angiotensin type 1 receptor-dependent increase in vascular reactivity may mitigate the fall in blood pressure observed with pendrin gene ablation

Electrical transport signatures of metallic surface state formation in the strongly-correlated insulator FeSb2

We present local and nonlocal electrical transport measurements of the correlated insulator FeSb$_2$. By employing wiring configurations that delineate between bulk- and surface-dominated conduction, we reveal the formation of a metallic surface state in FeSb$_2$ for temperatures $\lessapprox 5$~K. This result is corroborated by an angular rotation study of this material's magnetotransport, which also shows signatures of the transition from bulk- to surface-dominated conduction over the same temperature interval as the local/nonlocal transport divergence. Notable similarities with the topological Kondo insulator candidate SmB$_6$ are discussed

Listeriolysin O Causes ENaC Dysfunction in Human Airway Epithelial Cells.

Pulmonary permeability edema is characterized by reduced alveolar Na⁺ uptake capacity and capillary barrier dysfunction and is a potentially lethal complication of listeriosis. Apical Na⁺ uptake is mainly mediated by the epithelial sodium channel (ENaC) and initiates alveolar liquid clearance. Here we examine how listeriolysin O (LLO), the pore-forming toxin of Listeria monocytogenes, impairs the expression and activity of ENaC. To that purpose, we studied how sub-lytic concentrations of LLO affect negative and positive regulators of ENaC expression in the H441 airway epithelial cell line. LLO reduced expression of the crucial ENaC-α subunit in H441 cells within 2 h and this was preceded by activation of PKC-α, a negative regulator of the channel\u27s expression. At later time points, LLO caused a significant reduction in the phosphorylation of Sgk-1 at residue T256 and of Akt-1 at residue S473, both of which are required for full activation of ENaC. The TNF-derived TIP peptide prevented LLO-mediated PKC-α activation and restored phospho-Sgk-1-T256. The TIP peptide also counteracted the observed LLO-induced decrease in amiloride-sensitive Na⁺ current and ENaC-α expression in H441 cells. Intratracheally instilled LLO caused profound pulmonary edema formation in mice, an effect that was prevented by the TIP peptide; thus indicating the therapeutic potential of the peptide for the treatment of pore-forming toxin-associated permeability edema

On-chip single-photon subtraction by individual silicon vacancy centers in a laser-written diamond waveguide

Modifying light fields at single-photon level is a key challenge for upcoming quantum technologies and can be realized in a scalable manner through integrated quantum photonics. Laser-written diamond photonics offers three-dimensional fabrication capabilities and large mode-field diameters matched to fiber optic technology, though limiting the cooperativity at the single-emitter level. To realize large cooperativities, we combine excitation of single shallow-implanted silicon vacancy centers via large numerical aperture optics with detection assisted by laser-written type-II waveguides. We demonstrate single-emitter extinction measurements with a cooperativity of 0.153 and a beta factor of 13% yielding 15.3% as lower bound for the quantum efficiency of a single emitter. The transmission of resonant photons reveals single-photon subtraction from a quasi-coherent field resulting in super-Poissonian light statistics. Our architecture enables single quantum level light field engineering in an integrated design which can be fabricated in three dimensions and with a natural connectivity to optical fiber arrays.Comment: 8 pages, 4 figure

Super-poissonian light statistics from individual silicon vacancy centers coupled to a laser-written diamond waveguide

Modifying light fields at the single-photon level is a key challenge for upcoming quantum technologies and can be realized in a scalable manner through integrated quantum photonics. Laser-written diamond photonics offers 3D fabrication capabilities and large mode-field diameters matched to fiber optic technology, though limiting the cooperativity at the single-emitter level. To realize large coupling efficiencies, we combine excitation of single shallow-implanted silicon vacancy centers via high numerical aperture optics with detection assisted by laser-written type-II waveguides. We demonstrate single-emitter extinction measurements with a cooperativity of 0.0050 and a relative beta factor of 13%. The transmission of resonant photons reveals single-photon subtraction from a quasi-coherent field resulting in super-Poissonian light statistics. Our architecture enables light field engineering in an integrated design on the single quantum level although the intrinsic cooperativity is low. Laser-written structures can be fabricated in three dimensions and with a natural connectivity to optical fiber arrays

An Inventory and Assessment of Sample Sources for Survey Research with Agricultural Producers in the U.S.

Researchers need probability samples to collect representative survey data about the behaviors and attitudes of agricultural producers they study in relation to the natural resources that they manage, yet obtaining accurate and complete sampling frames is challenging. We extract data from a publication database to identify the most commonly used sampling frame sources in survey research of agricultural producers in the U.S., finding that government program participant lists are used most often, while private vendor samples are increasingly being purchased. Based on our research experience, we find that for many projects, private vendors can provide the most rigorous samples. Given that survey methods remain a useful and popular method for studying the behaviors and attitudes of producers on a variety of topics, such an assessment and guide is needed for researchers and practitioners

DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients

Background: Loss of A, B and H antigens from the red blood cells of patients with myeloid malignancies is a frequent occurrence. Previously, we have reported alterations in ABH antigens on the red blood cells of 55% of patients with myeloid malignancies. Methodology/Principal Findings: To determine the underlying molecular mechanisms of this loss, we assessed ABO allelic expression in 21 patients with ABH antigen loss previously identified by flow cytometric analysis as well as an additional 7 patients detected with ABH antigen changes by serology. When assessing ABO mRNA allelic expression, 6/12 (50%) patients with ABH antigen loss detected by flow cytometry and 5/7 (71%) of the patients with ABH antigen loss detected by serology had a corresponding ABO mRNA allelic loss of expression. We examined the ABO locus for copy number and DNA methylation alterations in 21 patients, 11 with loss of expression of one or both ABO alleles, and 10 patients with no detectable allelic loss of ABO mRNA expression. No loss of heterozygosity (LOH) at the ABO locus was observed in these patients. However in 8/11 (73%) patients with loss of ABO allelic expression, the ABO promoter was methylated compared with 2/10 (20%) of patients with no ABO allelic expression loss (P = 0.03). Conclusions/Significance: We have found that loss of ABH antigens in patients with hematological malignancies is associated with a corresponding loss of ABO allelic expression in a significant proportion of patients. Loss of ABO allelic expression was strongly associated with DNA methylation of the ABO promoter.Tina Bianco-Miotto, Damian J. Hussey, Tanya K. Day, Denise S. O'Keefe and Alexander Dobrovi

Integrated magnetometry platform with stackable waveguide-assisted detection channels for sensing arrays

The negatively charged nitrogen vacancy (N-V−) center in diamond has shown great success in nanoscale, high-sensitivity magnetometry. Efficient fluorescence detection is crucial for improving the sensitivity. Furthermore, integrated devices enable practicable sensors. Here, we present an integrated architecture which allows us to create N-V− centers a few nanometers below the diamond surface, and at the same time covering the entire mode field of femtosecond-laser-written type-II waveguides. We experimentally verify the coupling efficiency, showcase the detection of magnetic resonance signals through the waveguides and perform proof-of-principle experiments in magnetic field and temperature sensing. The sensing task can be operated via the waveguide without direct light illumination through the sample, which is important for magnetometry in biological systems that are sensitive to light. In the future, our approach will enable the development of two-dimensional sensing arrays facilitating spatially and temporally correlated magnetometry

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures