Spatial heterogeneity and peptide availability determine CTL killing efficiency in vivo

The rate at which a cytotoxic T lymphocyte (CTL) can survey for infected cells is a key ingredient of models of vertebrate immune responses to intracellular pathogens. Estimates have been obtained using in vivo cytotoxicity assays in which peptide-pulsed splenocytes are killed by CTL in the spleens of immunised mice. However the spleen is a heterogeneous environment and splenocytes comprise multiple cell types. Are some cell types intrinsically more susceptible to lysis than others? Quantitatively, what impacts are made by the spatial distribution of targets and effectors, and the level of peptide-MHC on the target cell surface? To address these questions we revisited the splenocyte killing assay, using CTL specific for an epitope of influenza virus. We found that at the cell population level T cell targets were killed more rapidly than B cells. Using modeling, quantitative imaging and in vitro killing assays we conclude that this difference in vivo likely reflects different migratory patterns of targets within the spleen and a heterogeneous distribution of CTL, with no detectable difference in the intrinsic susceptibilities of the two populations to lysis. Modeling of the stages involved in the detection and killing of peptide-pulsed targets in vitro revealed that peptide dose influenced the ability of CTL to form conjugates with targets but had no detectable effect on the probability that conjugation resulted in lysis, and that T cell targets took longer to lyse than B cells. We also infer that incomplete killing in vivo of cells pulsed with low doses of peptide may be due to a combination of heterogeneity in peptide uptake and the dissociation, but not internalisation, of peptide-MHC complexes. Our analyses demonstrate how population-averaged parameters in models of immune responses can be dissected to account for both spatial and cellular heterogeneity

Kernelization and Parameterized Algorithms for 3-Path Vertex Cover

A 3-path vertex cover in a graph is a vertex subset $C$ such that every path of three vertices contains at least one vertex from $C$. The parameterized 3-path vertex cover problem asks whether a graph has a 3-path vertex cover of size at most $k$. In this paper, we give a kernel of $5k$ vertices and an $O^*(1.7485^k)$-time and polynomial-space algorithm for this problem, both new results improve previous known bounds.Comment: in TAMC 2016, LNCS 9796, 201

On Arnold's 14 `exceptional' N=2 superconformal gauge theories

We study the four-dimensional superconformal N=2 gauge theories engineered by the Type IIB superstring on Arnold's 14 exceptional unimodal singularities (a.k.a. Arnold's strange duality list), thus extending the methods of 1006.3435 to singularities which are not the direct sum of minimal ones. In particular, we compute their BPS spectra in several `strongly coupled' chambers. From the TBA side, we construct ten new periodic Y-systems, providing additional evidence for the existence of a periodic Y-system for each isolated quasi-homogeneous singularity with $\hat c<2$ (more generally, for each N=2 superconformal theory with a finite BPS chamber whose chiral primaries have dimensions of the form N/l).Comment: 73 pages, 7 figure

The temperature and chronology of heavy-element synthesis in low-mass stars

Roughly half of the heavy elements (atomic mass greater than that of iron) are believed to be synthesized in the late evolutionary stages of stars with masses between 0.8 and 8 solar masses. Deep inside the star, nuclei (mainly iron) capture neutrons and progressively build up (through the slow-neutron-capture process, or s-process) heavier elements that are subsequently brought to the stellar surface by convection. Two neutron sources, activated at distinct temperatures, have been proposed: 13C and 22Ne, each releasing one neutron per alpha-particle (4He) captured. To explain the measured stellar abundances, stellar evolution models invoking the 13C neutron source (which operates at temperatures of about one hundred million kelvin) are favoured. Isotopic ratios in primitive meteorites, however, reflecting nucleosynthesis in the previous generations of stars that contributed material to the Solar System, point to higher temperatures (more than three hundred million kelvin), requiring at least a late activation of 22Ne. Here we report a determination of the s-process temperature directly in evolved low-mass giant stars, using zirconium and niobium abundances, independently of stellar evolution models. The derived temperature supports 13C as the s-process neutron source. The radioactive pair 93Zr-93Nb used to estimate the s-process temperature also provides, together with the pair 99Tc-99Ru, chronometric information on the time elapsed since the start of the s-process, which we determine to be one million to three million years.Comment: 30 pages, 10 figure

Tunable few-electron double quantum dots and Klein tunnelling in ultra-clean carbon nanotubes

Quantum dots defined in carbon nanotubes are a platform for both basic scientific studies and research into new device applications. In particular, they have unique properties that make them attractive for studying the coherent properties of single electron spins. To perform such experiments it is necessary to confine a single electron in a quantum dot with highly tunable barriers, but disorder has until now prevented tunable nanotube-based quantum-dot devices from reaching the single-electron regime. Here, we use local gate voltages applied to an ultra-clean suspended nanotube to confine a single electron in both a single quantum dot and, for the first time, in a tunable double quantum dot. This tunability is limited by a novel type of tunnelling that is analogous to that in the Klein paradox of relativistic quantum mechanics.Comment: 21 pages including supplementary informatio

Discrete Convex Functions on Graphs and Their Algorithmic Applications

The present article is an exposition of a theory of discrete convex functions on certain graph structures, developed by the author in recent years. This theory is a spin-off of discrete convex analysis by Murota, and is motivated by combinatorial dualities in multiflow problems and the complexity classification of facility location problems on graphs. We outline the theory and algorithmic applications in combinatorial optimization problems

General Argyres-Douglas Theory

We construct a large class of Argyres-Douglas type theories by compactifying six dimensional (2,0) A_N theory on a Riemann surface with irregular singularities. We give a complete classification for the choices of Riemann surface and the singularities. The Seiberg-Witten curve and scaling dimensions of the operator spectrum are worked out. Three dimensional mirror theory and the central charges a and c are also calculated for some subsets, etc. Our results greatly enlarge the landscape of N=2 superconformal field theory and in fact also include previous theories constructed using regular singularity on the sphere.Comment: 55 pages, 20 figures, minor revision and typos correcte

Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH