BioScript: programming safe chemistry on laboratories-on-a-chip

This paper introduces BioScript, a domain-specific language (DSL) for programmable biochemistry which executes on emerging microfluidic platforms. The goal of this research is to provide a simple, intuitive, and type-safe DSL that is accessible to life science practitioners. The novel feature of the language is its syntax, which aims to optimize human readability; the technical contributions of the paper include the BioScript type system and relevant portions of its compiler. The type system ensures that certain types of errors, specific to biochemistry, do not occur, including the interaction of chemicals that may be unsafe. The compiler includes novel optimizations that place biochemical operations to execute concurrently on a spatial 2D array platform on the granularity of a control flow graph, as opposed to individual basic blocks. Results are obtained using both a cycle-accurate microfluidic simulator and a software interface to a real-world platform

Induced Rotation in 3D Simulations of Core Collapse Supernovae: Implications for Pulsar Spins

It has been suggested that the observed rotation periods of radio pulsars might be induced by a non-axisymmetric spiral-mode instability in the turbulent region behind the stalled supernova bounce shock, even if the progenitor core was not initially rotating. In this paper, using the three-dimensional AMR code CASTRO with a realistic progenitor and equation of state and a simple neutrino heating and cooling scheme, we present a numerical study of the evolution in 3D of the rotational profile of a supernova core from collapse, through bounce and shock stagnation, to delayed explosion. By the end of our simulation ($\sim$420 ms after core bounce), we do not witness significant spin up of the proto-neutron star core left behind. However, we do see the development before explosion of strong differential rotation in the turbulent gain region between the core and stalled shock. Shells in this region acquire high spin rates that reach $\sim$$150\,$ Hz, but this region contains too little mass and angular momentum to translate, even if left behind, into rapid rotation for the full neutron star. We find also that much of the induced angular momentum is likely to be ejected in the explosion, and moreover that even if the optimal amount of induced angular momentum is retained in the core, the resulting spin period is likely to be quite modest. Nevertheless, induced periods of seconds are possible.Comment: Accepted to the Astrophysical Journa

New developments in the treatment of metastatic melanoma – role of dabrafenib–trametinib combination therapy

Development of selective inhibitors of BRAF has improved the survival of patients with BRAF-mutant melanoma. The progression-free survival after treatment with a BRAF inhibitor is modest, however, and BRAF inhibitors induce cutaneous toxicity, likely due to paradoxical activation of the mitogen-activated protein kinase pathway. Combining selective BRAF and MEK inhibition, such as the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib, has been shown to improve the response rate and progression-free survival in patients with advanced melanoma while significantly alleviating the paradoxical activation of mitogen-activated protein kinase. This combination treatment results in a reduction in skin toxicity relative to that seen with a BRAF inhibitor alone; however, addition of the MEK inhibitor adds other toxicities, such as pyrexia and gastrointestinal or ocular toxicity. While combined BRAF–MEK inhibition appears primed to become a standard molecular approach for BRAF-mutant melanoma, the utility of the combination has to be considered in the rapidly changing landscape of immunotherapeutics, such as immune checkpoint blockade using anti-cytotoxic T lymphocyte antigen-4 and anti-programmed death-1/programmed death-L1 antibodies. Here we review the development of the dabrafenib plus trametinib combination, the characteristics of each drug and the combination, and the role of this combination in the management of patients with BRAF-mutant melanoma

Wellington : a novel method for the accurate identification of digital genomic footprints from DNase-seq data

The expression of eukaryotic genes is regulated by cis-regulatory elements such as promoters and enhancers, which bind sequence-specific DNA-binding proteins. One of the great challenges in the gene regulation field is to characterise these elements. This involves the identification of transcription factor (TF) binding sites within regulatory elements that are occupied in a defined regulatory context. Digestion with DNase and the subsequent analysis of regions protected from cleavage (DNase footprinting) has for many years been used to identify specific binding sites occupied by TFs at individual cis-elements with high resolution. This methodology has recently been adapted for high-throughput sequencing (DNase-seq). In this study, we describe an imbalance in the DNA strand-specific alignment information of DNase-seq data surrounding protein–DNA interactions that allows accurate prediction of occupied TF binding sites. Our study introduces a novel algorithm, Wellington, which considers the imbalance in this strand-specific information to efficiently identify DNA footprints. This algorithm significantly enhances specificity by reducing the proportion of false positives and requires significantly fewer predictions than previously reported methods to recapitulate an equal amount of ChIP-seq data. We also provide an open-source software package, pyDNase, which implements the Wellington algorithm to interface with DNase-seq data and expedite analyses

Self-similarities in the frequency-amplitude space of a loss-modulated CO2_2 laser

We show the standard two-level continuous-time model of loss-modulated CO$_2$ lasers to display the same regular network of self-similar stability islands known so far to be typically present only in discrete-time models based on mappings. For class B laser models our results suggest that, more than just convenient surrogates, discrete mappings in fact could be isomorphic to continuous flows.Comment: (5 low-res color figs; for ALL figures high-res PDF: http://www.if.ufrgs.br/~jgallas/jg_papers.html

Time-Evolution of a Fractal Distribution: Particle Concentrations in Free-Surface Turbulence

Steady-state turbulence is generated in a tank of water and the trajectories of particles forming a compressible system on the surface are tracked in time. The initial uniformly distributed floating particles coagulate and form a fractal distribution, a rare manifestation of a fractal object observable in real-space. The surface pattern reaches a steady state in approximately 1 s. Measurements are made of the fractal dimensions $D_q(t)$ ($q=1$ to $6$) of the floating particles starting with the uniform distribution $D_q(0)$ = 2 for Taylor Microscale Reynolds number $Re_{\lambda} \simeq 160$. Focus is on the the time-evolution of the correlation dimension $D_2(t)$ as the steady state is approached. This steady state is reached in several large eddy turnover times and does so at an exponential rate

Complex Radio Spectral Energy Distributions in Luminous and Ultraluminous Infrared Galaxies

We use the Expanded Very Large Array to image radio continuum emission from local luminous and ultraluminous infrared galaxies (LIRGs and ULIRGs) in 1 GHz windows centered at 4.7, 7.2, 29, and 36 GHz. This allows us to probe the integrated radio spectral energy distribution (SED) of the most energetic galaxies in the local universe. The 4-8 GHz flux densities agree well with previous measurements. They yield spectral indices \alpha \approx -0.67 (where F_\nu \propto \nu^\alpha) with \pm 0.15 (1\sigma) scatter, typical of nonthermal (synchrotron) emission from star-forming galaxies. The contrast of our 4-8 GHz data with literature 1.5 and 8.4 GHz flux densities gives further evidence for curvature of the radio SED of U/LIRGs. The SED appears flatter near \sim 1 GHz than near \sim 6 GHz, suggesting significant optical depth effects at the lower frequencies. The high frequency (28-37 GHz) flux densities are low compared to extrapolations from the 4-8 GHz data. We confirm and extend to higher frequency a previously observed deficit of high frequency radio emission for luminous starburst galaxies.Comment: 7 pages, 3 figures, 1 table, accepted for publication in the EVLA Special Issue of ApJ Letter

A Detection of Sgr A* in the far infrared

We report the first detection of the Galactic Centre massive black hole, Sgr~A*, in the far infrared. Our measurements were obtained with PACS on board the \emph{Herschel} satellite at $100~\mathrm{\mu m}$ and $160~\mathrm{\mu m}$. While the warm dust in the Galactic Centre is too bright to allow for a direct detection of Sgr~A*, we measure a significant and simultaneous variation of its flux of $\Delta F_{\nu\widehat{=}160 ~\mathrm{\mu m}} = (0.27\pm0.06)~\mathrm{Jy}$ and $\Delta F_{\nu\widehat{=}100 ~\mathrm{\mu m}}= (0.16\pm0.10)~\mathrm{Jy}$ during one observation. The significance level of the $160 ~\mathrm{\mu m}$ band variability is $4.5\sigma$ and the corresponding $100 ~\mathrm{\mu m}$ band variability is significant at $1.6\sigma$. We find no example of an equally significant false positive detection. Conservatively assuming a variability of $25\%$ in the FIR, we can provide upper limits to the flux. Comparing the latter with theoretical models we find that 1D RIAF models have difficulties explaining the observed faintness. However, the upper limits are consistent with modern ALMA and VLA observations. Our upper limits provide further evidence for a spectral peak at $\sim 10^{12} ~ \mathrm{Hz}$ and constrain the number density of $\gamma \sim 100$ electrons in the accretion disk and or outflow.Comment: accepted for publication in AP