Modelling trait-dependent speciation with approximate Bayesian computation

Phylogeny is the field of modelling the temporal discrete dynamics of speciation. Complex models can nowadays be studied using the Approximate Bayesian Computation approach which avoids likelihood calculations. The field's progression is hampered by the lack of robust software to estimate the numerous parameters of the speciation process. In this work we present an R package, pcmabc, based on Approximate Bayesian Computations, that implements three novel phylogenetic algorithms for trait-dependent speciation modelling. Our phylogenetic comparative methodology takes into account both the simulated traits and phylogeny, attempting to estimate the parameters of the processes generating the phenotype and the trait. The user is not restricted to a predefined set of models and can specify a variety of evolutionary and branching models. We illustrate the software with a simulation-reestimation study focused around the branching Ornstein-Uhlenbeck process, where the branching rate depends non-linearly on the value of the driving Ornstein-Uhlenbeck process. Included in this work is a tutorial on how to use the software

Strontium optical lattice clocks for practical realization of the metre and secondary representation of the second

We present a system of two independent strontium optical lattice standards probed with a single shared ultra-narrow laser. The absolute frequency of the clocks can be verified by the use of Er:fiber optical frequency comb with the GPS-disciplined Rb frequency standard. We report hertz-level spectroscopy of the clock line and measurements of frequency stability of the two strontium optical lattice clocks.Comment: This is an author-created, un-copyedited version of an article accepted for publication in Meas. Sci. Technol. The publisher is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at doi:10.1088/0957-0233/26/7/07520

Development and operational experience of magnetic horn system for T2K experiment

A magnetic horn system to be operated at a pulsed current of 320 kA and to survive high-power proton beam operation at 750 kW was developed for the T2K experiment. The first set of T2K magnetic horns was operated for over 12 million pulses during the four years of operation from 2010 to 2013, under a maximum beam power of 230 kW, and $6.63\times10^{20}$ protons were exposed to the production target. No significant damage was observed throughout this period. This successful operation of the T2K magnetic horns led to the discovery of the $\nu_{\mu}\rightarrow\nu_e$ oscillation phenomenon in 2013 by the T2K experiment. In this paper, details of the design, construction, and operation experience of the T2K magnetic horns are described.Comment: 22 pages, 40 figures, also submitted to Nuclear Instrument and Methods in Physics Research,

Combinations of cocoa antioxidants: what they tell us about the chemopreventive relevance of interactions between food components?

Antioxidant properties of polyphenols are believed to underlie cocoa chemopreventive potential. However, it has been not recognized if these effects are mainly caused by the most abundant components or result from concerted action of major and minor cocoa bioactives as proposed by food synergy concept. This study was aimed at resolving this question. Initially, the cocoa extract composition was determined by HPLC-DAD-MS. Then, bioactivities of cocoa extract and a series of artificial mixtures of cocoa phytochemicals were tested to compare their redox properties in cell-free system and redox-associated biological effects in human colon cancer HT29 cells serving as a model of human alimentary tract. Under cell-free conditions, DPPH test as well as differential pulse voltammetry showed the highest antioxidant activity for cocoa powder extract (CE), but surprisingly, did not reveal any dose-dependent differences between mixtures despite growing concentration and complexity of antioxidants. Basically, to the same conclusion lead determinations of cellular antioxidant activity; CE was the most efficient in cell protection against ROS whereby concentration of catechins in studied solutions had to be above 10 μM to override cellular redox homeostasis. Cell growth inhibition was dose-dependent only for mixtures that consisted of main catechins at narrow range of low concentrations (0.01 – 1 μM C+EC). Neither clear relationship between composition of cocoa phytochemicals and nutrigenomic activity of CE and matching mixtures was spotted. Therefore, our study indicates that the bioactivity of non-toxic complex natural mixtures such as cocoa is strongly affected by interactions between their components, as predicted by food synergy.Nutraceuticals in balancing redox status in ageing and age-related diseases WGs Meeting of the NutRedOx COST Action CA16112 Belgrade, March 2-3, 202

A magnetically-driven piston pump for ultra-clean applications

A magnetically driven piston pump for xenon gas recirculation is presented. The pump is designed to satisfy extreme purity and containment requirements, as is appropriate for the recirculation of isotopically enriched xenon through the purification system and large liquid xenon TPC of EXO-200. The pump, using sprung polymer gaskets, is capable of pumping more than 16 standard liters per minute (SLPM) of xenon gas with 750 torr differential pressure.Comment: 6 pages, 5 figure

A liquid xenon ionization chamber in an all-fluoropolymer vessel

A novel technique has been developed to build vessels for liquid xenon ionization detectors entirely out of ultra-clean fluoropolymer. We describe the advantages in terms of low radioactivity contamination, provide some details of the construction techniques, and show the energy resolution achieved with a prototype all-fluoropolymer ionization detector.Comment: 12 pages, 9 figure

NK cells with tissue-resident traits shape response to immunotherapy by inducing adaptive antitumor immunity

T cell-directed cancer immunotherapy often fails to generate lasting tumor control. Harnessing additional effectors of the immune response against tumors may strengthen the clinical benefit of immunotherapies. Here, we demonstrate that therapeutic targeting of the interferon-γ (IFN-γ)-interleukin-12 (IL-12) pathway relies on the ability of a population of natural killer (NK) cells with tissue-resident traits to orchestrate an antitumor microenvironment. In particular, we used an engineered adenoviral platform as a tool for intratumoral IL-12 immunotherapy (AdV5-IL-12) to generate adaptive antitumor immunity. Mechanistically, we demonstrate that AdV5-IL-12 is capable of inducing the expression of CC-chemokine ligand 5 (CCL5) in CD49a+ NK cells both in tumor mouse models and tumor specimens from patients with cancer. AdV5-IL-12 imposed CCL5-induced type I conventional dendritic cell (cDC1) infiltration and thus increased DC-CD8 T cell interactions. A similar observation was made for other IFN-γ-inducing therapies such as Programmed cell death 1 (PD-1) blockade. Conversely, failure to respond to IL-12 and PD-1 blockade in tumor models with low CD49a+ CXCR6+ NK cell infiltration could be overcome by intratumoral delivery of CCL5. Thus, therapeutic efficacy depends on the abundance of NK cells with tissue-resident traits and, specifically, their capacity to produce the DC chemoattractant CCL5. Our findings reveal a barrier for T cell-focused therapies and offer mechanistic insights into how T cell-NK cell-DC cross-talk can be enhanced to promote antitumor immunity and overcome resistance

NK cells with tissue-resident traits shape response to immunotherapy by inducing adaptive antitumor immunity

T cell-directed cancer immunotherapy often fails to generate lasting tumor control. Harnessing additional effectors of the immune response against tumors may strengthen the clinical benefit of immunotherapies. Here, we demonstrate that therapeutic targeting of the interferon-γ (IFN-γ)-interleukin-12 (IL-12) pathway relies on the ability of a population of natural killer (NK) cells with tissue-resident traits to orchestrate an antitumor microenvironment. In particular, we used an engineered adenoviral platform as a tool for intratumoral IL-12 immunotherapy (AdV5-IL-12) to generate adaptive antitumor immunity. Mechanistically, we demonstrate that AdV5-IL-12 is capable of inducing the expression of CC-chemokine ligand 5 (CCL5) in CD49a; +; NK cells both in tumor mouse models and tumor specimens from patients with cancer. AdV5-IL-12 imposed CCL5-induced type I conventional dendritic cell (cDC1) infiltration and thus increased DC-CD8 T cell interactions. A similar observation was made for other IFN-γ-inducing therapies such as Programmed cell death 1 (PD-1) blockade. Conversely, failure to respond to IL-12 and PD-1 blockade in tumor models with low CD49a; +; CXCR6; +; NK cell infiltration could be overcome by intratumoral delivery of CCL5. Thus, therapeutic efficacy depends on the abundance of NK cells with tissue-resident traits and, specifically, their capacity to produce the DC chemoattractant CCL5. Our findings reveal a barrier for T cell-focused therapies and offer mechanistic insights into how T cell-NK cell-DC cross-talk can be enhanced to promote antitumor immunity and overcome resistance