Optimization viewpoint on Kalman smoothing, with applications to robust and sparse estimation

In this paper, we present the optimization formulation of the Kalman filtering and smoothing problems, and use this perspective to develop a variety of extensions and applications. We first formulate classic Kalman smoothing as a least squares problem, highlight special structure, and show that the classic filtering and smoothing algorithms are equivalent to a particular algorithm for solving this problem. Once this equivalence is established, we present extensions of Kalman smoothing to systems with nonlinear process and measurement models, systems with linear and nonlinear inequality constraints, systems with outliers in the measurements or sudden changes in the state, and systems where the sparsity of the state sequence must be accounted for. All extensions preserve the computational efficiency of the classic algorithms, and most of the extensions are illustrated with numerical examples, which are part of an open source Kalman smoothing Matlab/Octave package.Comment: 46 pages, 11 figure

What happens if you single out? An experiment

We present an experiment investigating the effects of singling out an individual on trust and trustworthiness. We find that (a) trustworthiness falls if there is a singled out subject; (b) non-singled out subjects discriminate against the singled out subject when they are not responsible of the distinct status of this person; (c) under a negative frame, the singled out subject returns significantly less; (d) under a positive frame, the singled out subject behaves bimodally, either selecting very low or very high return rates. Overall, singling out induces a negligible effect on trust but is potentially disruptive for trustworthiness

Trans-eQTLs Reveal That Independent Genetic Variants Associated with a Complex Phenotype Converge on Intermediate Genes, with a Major Role for the HLA

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Blow-up profile of rotating 2D focusing Bose gases

We consider the Gross-Pitaevskii equation describing an attractive Bose gas trapped to a quasi 2D layer by means of a purely harmonic potential, and which rotates at a fixed speed of rotation $\Omega$. First we study the behavior of the ground state when the coupling constant approaches $a\_*$ , the critical strength of the cubic nonlinearity for the focusing nonlinear Schr{\"o}dinger equation. We prove that blow-up always happens at the center of the trap, with the blow-up profile given by the Gagliardo-Nirenberg solution. In particular, the blow-up scenario is independent of $\Omega$, to leading order. This generalizes results obtained by Guo and Seiringer (Lett. Math. Phys., 2014, vol. 104, p. 141--156) in the non-rotating case. In a second part we consider the many-particle Hamiltonian for $N$ bosons, interacting with a potential rescaled in the mean-field manner $--a\_N N^{2\beta--1} w(N^{\beta} x), with$w$a positive function such that$\int\_{\mathbb{R}^2} w(x) dx = 1$. Assuming that$\beta < 1/2$and that$a\_N \to a\_*$sufficiently slowly, we prove that the many-body system is fully condensed on the Gross-Pitaevskii ground state in the limit$N \to \infty$

Trapped lipopolysaccharide and LptD intermediates reveal lipopolysaccharide translocation steps across the Escherichia coli outer membrane

Lipopolysaccharide (LPS) is a main component of the outer membrane of Gram-negative bacteria, which is essential for the vitality of most Gram-negative bacteria and plays a critical role for drug resistance. LptD/E complex forms a N-terminal LPS transport slide, a hydrophobic intramembrane hole and the hydrophilic channel of the barrel, for LPS transport, lipid A insertion and core oligosaccharide and O-antigen polysaccharide translocation, respectively. However, there is no direct evidence to confirm that LptD/E transports LPS from the periplasm to the external leaflet of the outer membrane. By replacing LptD residues with an unnatural amino acid p-benzoyl-L-phenyalanine (pBPA) and UV-photo-cross-linking in E.coli, the translocon and LPS intermediates were obtained at the N-terminal domain, the intramembrane hole, the lumenal gate, the lumen of LptD channel, and the extracellular loop 1 and 4, providing the first direct evidence and “snapshots” to reveal LPS translocation steps across the outer membrane

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

Pyrimidine biosynthesis is not an essential function for trypanosoma brucei bloodstream forms

&lt;p&gt;Background: African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host, but it is unknown whether either process is essential to the parasite.&lt;/p&gt; &lt;p&gt;Methodology/Principal Findings: Pyrimidine requirements for growth were investigated using strictly pyrimidine-free media, with or without single added pyrimidine sources. Growth rates of wild-type bloodstream form Trypanosoma brucei brucei were unchanged in pyrimidine-free medium. The essentiality of the de novo pyrimidine biosynthesis pathway was studied by knocking out the PYR6-5 locus that produces a fusion product of orotate phosphoribosyltransferase (OPRT) and Orotidine Monophosphate Decarboxylase (OMPDCase). The pyrimidine auxotroph was dependent on a suitable extracellular pyrimidine source. Pyrimidine starvation was rapidly lethal and non-reversible, causing incomplete DNA content in new cells. The phenotype could be rescued by addition of uracil; supplementation with uridine, 2′deoxyuridine, and cytidine allowed a diminished growth rate and density. PYR6-5−/− trypanosomes were more sensitive to pyrimidine antimetabolites and displayed increased uracil transport rates and uridine phosphorylase activity. Pyrimidine auxotrophs were able to infect mice although the infection developed much more slowly than infection with the parental, prototrophic trypanosome line.&lt;/p&gt; &lt;p&gt;Conclusions/Significance: Pyrimidine salvage was not an essential function for bloodstream T. b. brucei. However, trypanosomes lacking de novo pyrimidine biosynthesis are completely dependent on an extracellular pyrimidine source, strongly preferring uracil, and display reduced infectivity. As T. brucei are able to salvage sufficient pyrimidines from the host environment, the pyrimidine biosynthesis pathway is not a viable drug target, although any interruption of pyrimidine supply was lethal.&lt;/p&gt

Electrical control over single hole spins in nanowire quantum dots

Single electron spins in semiconductor quantum dots (QDs) are a versatile platform for quantum information processing, however controlling decoherence remains a considerable challenge. Recently, hole spins have emerged as a promising alternative. Holes in III-V semiconductors have unique properties, such as strong spin-orbit interaction and weak coupling to nuclear spins, and therefore have potential for enhanced spin control and longer coherence times. Weaker hyperfine interaction has already been reported in self-assembled quantum dots using quantum optics techniques. However, challenging fabrication has so far kept the promise of hole-spin-based electronic devices out of reach in conventional III-V heterostructures. Here, we report gate-tuneable hole quantum dots formed in InSb nanowires. Using these devices we demonstrate Pauli spin blockade and electrical control of single hole spins. The devices are fully tuneable between hole and electron QDs, enabling direct comparison between the hyperfine interaction strengths, g-factors and spin blockade anisotropies in the two regimes

Influence of wiring cost on the large-scale architecture of human cortical connectivity

In the past two decades some fundamental properties of cortical connectivity have been discovered: small-world structure, pronounced hierarchical and modular organisation, and strong core and rich-club structures. A common assumption when interpreting results of this kind is that the observed structural properties are present to enable the brain's function. However, the brain is also embedded into the limited space of the skull and its wiring has associated developmental and metabolic costs. These basic physical and economic aspects place separate, often conflicting, constraints on the brain's connectivity, which must be characterized in order to understand the true relationship between brain structure and function. To address this challenge, here we ask which, and to what extent, aspects of the structural organisation of the brain are conserved if we preserve specific spatial and topological properties of the brain but otherwise randomise its connectivity. We perform a comparative analysis of a connectivity map of the cortical connectome both on high- and low-resolutions utilising three different types of surrogate networks: spatially unconstrained (‘random’), connection length preserving (‘spatial’), and connection length optimised (‘reduced’) surrogates. We find that unconstrained randomisation markedly diminishes all investigated architectural properties of cortical connectivity. By contrast, spatial and reduced surrogates largely preserve most properties and, interestingly, often more so in the reduced surrogates. Specifically, our results suggest that the cortical network is less tightly integrated than its spatial constraints would allow, but more strongly segregated than its spatial constraints would necessitate. We additionally find that hierarchical organisation and rich-club structure of the cortical connectivity are largely preserved in spatial and reduced surrogates and hence may be partially attributable to cortical wiring constraints. In contrast, the high modularity and strong s-core of the high-resolution cortical network are significantly stronger than in the surrogates, underlining their potential functional relevance in the brain

How I report breast magnetic resonance imaging studies for breast cancer staging and screening

Magnetic resonance imaging (MRI) of the breast is the most sensitive imaging technique for the diagnosis and local staging of primary breast cancer and yet, despite the fact that it has been in use for 20 years, there is little evidence that its widespread uncritical adoption has had a positive impact on patient-related outcomes. This has been attributed previously to the low specificity that might be expected with such a sensitive modality, but with modern techniques and protocols, the specificity and positive predictive value for malignancy can exceed that of breast ultrasound and mammography. A more likely explanation is that historically, clinicians have acted on MRI findings and altered surgical plans without prior histological confirmation. Furthermore, modern adjuvant therapy for breast cancer has improved so much that it has become a very tall order to show a an improvement in outcomes such as local recurrence rates. In order to obtain clinically useful information, it is necessary to understand the strengths and weaknesses of the technique and the physiological processes reflected in breast MRI. An appropriate indication for the scan, proper patient preparation and good scan technique, with rigorous quality assurance, are all essential prerequisites for a diagnostically relevant study. The use of recognised descriptors from a standardised lexicon is helpful, since assessment can then dictate subsequent recommendations for management, as in the American College of Radiology BI-RADS (Breast Imaging Reporting and Data System) lexicon (Morris et al., ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System, 2013). It also enables audit of the service. However, perhaps the most critical factor in the generation of a meaningful report is for the reporting radiologist to have a thorough understanding of the clinical question and of the findings that will influence management. This has never been more important than at present, when we are in the throes of a remarkable paradigm shift in the treatment of both early stage and locally advanced breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40644-016-0078-0) contains supplementary material, which is available to authorized users