Planar cell polarity genes Frizzled3a, Vangl2, and Scribble are required for spinal commissural axon guidance

Background A fundamental feature of early nervous system development is the guidance of axonal projections to their targets in order to assemble neural circuits that control behavior. Spinal commissural neurons are an attractive model to investigate the multiple guidance cues that control growth cone navigation both pre- and post-midline crossing, as well as along both the dorsal–ventral (D–V) and anterior–posterior (A–P) axes. Accumulating evidence suggests that guidance of spinal commissural axons along the A–P axis is dependent on components of the planar cell polarity (PCP) signaling pathway. In the zebrafish, the earliest born spinal commissural neuron to navigate the midline and turn rostrally is termed commissural primary ascending (CoPA). Unlike mammalian systems, CoPA axons cross the midline as a single axon and allow an analysis of the role of PCP components in anterior pathfinding in single pioneering axons. Results Here, we establish CoPA cells in the zebrafish spinal cord as a model system for investigating the molecular function of planar cell polarity signaling in axon guidance. Using mutant analysis, we show that the functions of Fzd3a and Vangl2 in the anterior turning of commissural axons are evolutionarily conserved in teleosts. We extend our findings to reveal a role for the PCP gene scribble in the anterior guidance of CoPA axons. Analysis of single CoPA axons reveals that these commissural axons become responsive to PCP-dependent anterior guidance cues even prior to midline crossing. When midline crossing is prevented by dcc gene knockdown, ipsilateral CoPA axons still extend axons anteriorly in response to A–P guidance cues. We show that this ipsilateral anterior pathfinding that occurs in the absence of midline crossing is dependent on PCP signaling. Conclusion Our results demonstrate that anterior guidance decisions by CoPA axons are dependent on the function of planar cell polarity genes both prior to and after midline crossing

Specific wavelength colorimeter

A self contained, specific wavelength, single beam colorimeter is described for direct spectrophotometric measurement of the concentration of a given solute in a test sample. An electrical circuit employing a photoconductive cell converts the optical output into a linear, directly readable meter output. The colorimeter is simple to operate and is adapted for use in zero gravity conditions. In a specific application, the colorimeter is designed to analyze the concentration of iodine in potable water carried aboard a space vehicle such as the 4B stage of Skylab

European Paediatric Formulation Initiative (EuPFI)-Formulating Ideas for Better Medicines for Children.

© American Association of Pharmaceutical Scientists 2016, published by Springer US, available online at doi: https://doi.org/10.1208/s12249-016-0584-1The European Paediatric Formulation Initiative (EuPFI), founded in 2007, aims to promote and facilitate the preparation of better and safe medicines for children through linking research and information dissemination. It brings together the capabilities of the industry, academics, hospitals, and regulators within a common platform in order to scope the solid understanding of the major issues, which will underpin the progress towards the future of paediatric medicines we want.The EuPFI was formed in parallel to the adoption of regulations within the EU and USA and has served as a community that drives research and dissemination through publications and the organisation of annual conferences. The membership and reach of this group have grown since its inception in 2007 and continue to develop and evolve to meet the continuing needs and ambitions of research into and development of age appropriate medicines. Five diverse workstreams (age-appropriate medicines, Biopharmaceutics, Administration Devices, Excipients and Taste Assessment & Taste Masking (TATM)) direct specific workpackages on behalf of the EuPFI. Furthermore, EuPFI interacts with multiple diverse professional groups across the globe to ensure efficient working in the area of paediatric medicines. Strong commitment and active involvement of all EuPFI stakeholders have proved to be vital to effectively address knowledge gaps related to paediatric medicines, discuss potential areas for further research and identify issues that need more attention and analysis in the future.Peer reviewedFinal Accepted Versio

HeI in the central Giant HII Region of NGC 5253. A 2D observational approach to collisional and radiative transfer effects

ABRIDGED: NGC5253 is an ideal laboratory for detailed studies of starburst galaxies. We present for the first time in a starburst galaxy a 2D study of the spatial behavior of collisional and radiative transfer effects in He^+. The HeI lines are analysed based on data obtained with FLAMES and GMOS. Collisional effects are negligible for transitions in the singlet cascade while relatively important for those in the triplet cascade. In particular, they can contribute up to 20% of the flux in the HeIl7065 line. Radiative transfer effects are important over an extended and circular area of 30pc in diameter centered at the Super Star Clusters. HeI abundance, y^+, has been mapped using extinction corrected fluxes of six HeI lines, realistic assumptions for T_e, n_e, and the stellar absorption equivalent width as well as the most recent emissivities. We found a mean of 10^3 y^+ ~80.3 over the mapped area. The relation between the excitation and the total helium abundance, y_tot, is consistent with no abundance gradient. Uncertainties in the derivation of He abundances are dominated by the adopted assumptions. We illustrated the difficulty of detecting a putative He enrichment due to the presence of Wolf-Rayet stars in the main GHIIR. Data are marginally consistent with an excess in the N/He ratio in the N enriched area of the order of both, the atmospheric N/He ratios in WR stars and the uncertainties estimated for the N/He ratios.Comment: Accepted in Astronomy and Astrophysics; the emissivities presented in the Corrigendum, Porter et al. 2013, arXiv:1303.5115, have been include

Local search for stable marriage problems

The stable marriage (SM) problem has a wide variety of practical applications, ranging from matching resident doctors to hospitals, to matching students to schools, or more generally to any two-sided market. In the classical formulation, n men and n women express their preferences (via a strict total order) over the members of the other sex. Solving a SM problem means finding a stable marriage where stability is an envy-free notion: no man and woman who are not married to each other would both prefer each other to their partners or to being single. We consider both the classical stable marriage problem and one of its useful variations (denoted SMTI) where the men and women express their preferences in the form of an incomplete preference list with ties over a subset of the members of the other sex. Matchings are permitted only with people who appear in these lists, an we try to find a stable matching that marries as many people as possible. Whilst the SM problem is polynomial to solve, the SMTI problem is NP-hard. We propose to tackle both problems via a local search approach, which exploits properties of the problems to reduce the size of the neighborhood and to make local moves efficiently. We evaluate empirically our algorithm for SM problems by measuring its runtime behaviour and its ability to sample the lattice of all possible stable marriages. We evaluate our algorithm for SMTI problems in terms of both its runtime behaviour and its ability to find a maximum cardinality stable marriage.For SM problems, the number of steps of our algorithm grows only as O(nlog(n)), and that it samples very well the set of all stable marriages. It is thus a fair and efficient approach to generate stable marriages.Furthermore, our approach for SMTI problems is able to solve large problems, quickly returning stable matchings of large and often optimal size despite the NP-hardness of this problem.Comment: 12 pages, Proc. COMSOC 2010 (Third International Workshop on Computational Social Choice

Using HINODE/Extreme-Ultraviolet Imaging Spectrometer to confirm a seismologically inferred coronal temperature

The Extreme-Ultraviolet Imaging Spectrometer on board the HINODE satellite is used to examine the loop system described in Marsh et al. (2009) by applying spectroscopic diagnostic methods. A simple isothermal mapping algorithm is applied to determine where the assumption of isothermal plasma may be valid, and the emission measure locii technique is used to determine the temperature profile along the base of the loop system. It is found that, along the base, the loop has a uniform temperature profile with a mean temperature of 0.89 +- 0.09 MK which is in agreement with the temperature determined seismologically in Marsh et al. (2009), using observations interpreted as the slow magnetoacoustic mode. The results further strengthen the slow mode interpretation, propagation at a uniform sound speed, and the analysis method applied in Marsh et al. (2009). It is found that it is not possible to discriminate between the slow mode phase speed and the sound speed within the precision of the present observations

Review of operational aspects of initial experiments utilizing the U.S. MLS

An exercise to support the Federal Aviation Administration in demonstrating the U.S. candidate for an international microwave landing system (MLS) was conducted by NASA. During this demonstration the MLS was utilized to provide the TCV Boeing 737 research airplane with guidance for automatic control during transition from conventional RNAV to MLS RNAV in curved, descending flight; flare; touchdown; and roll-out. Flight profiles, system configuration, displays, and operating procedures used in the demonstration are described, and preliminary results of flight data analysis are discussed. Recent experiences with manually controlled flight in the NAFEC MLS environment are also discussed. The demonstration shows that in automatic three-dimensional flight, the volumetric signal coverage of the MLS can be exploited to enable a commercial carrier class airplane to perform complex curved, descending paths with precision turns into short final approaches terminating in landing and roll-out, even when subjected to strong and gusty tail and cross wind components and severe wind shear

The Phase Diagram of 1-in-3 Satisfiability Problem

We study the typical case properties of the 1-in-3 satisfiability problem, the boolean satisfaction problem where a clause is satisfied by exactly one literal, in an enlarged random ensemble parametrized by average connectivity and probability of negation of a variable in a clause. Random 1-in-3 Satisfiability and Exact 3-Cover are special cases of this ensemble. We interpolate between these cases from a region where satisfiability can be typically decided for all connectivities in polynomial time to a region where deciding satisfiability is hard, in some interval of connectivities. We derive several rigorous results in the first region, and develop the one-step--replica-symmetry-breaking cavity analysis in the second one. We discuss the prediction for the transition between the almost surely satisfiable and the almost surely unsatisfiable phase, and other structural properties of the phase diagram, in light of cavity method results.Comment: 30 pages, 12 figure

Both doublecortin and doublecortin-like kinase play a role in cortical interneuron migration

Type I lissencephaly, a genetic disease characterized by disorganized cortical layers and gyral abnormalities, is associated with severe cognitive impairment and epilepsy. Two genes, LIS1 and doublecortin (DCX), have been shown to be responsible for a large proportion of cases of type I lissencephaly. Both genes encode microtubule-associated proteins that have been shown to be important for radial migration of cortical pyramidal neurons. To investigate whether DCX also plays a role in cortical interneuron migration, we inactivated DCX in the ganglionic eminence of rat embryonic day 17 brain slices using short hairpin RNA. We found that, when DCX expression was blocked, the migration of interneurons from the ganglionic eminence to the cerebral cortex was slowed but not absent, similar to what had previously been reported for radial neuronal migration. In addition, the processes of DCX-deficient migrating interneurons were more branched than their counterparts in control experiments. These effects were rescued by DCX overexpression, confirming the specificity to DCX inactivation. A similar delay in interneuron migration was observed when Doublecortin-like kinase (DCLK), a microtubule-associated protein related to DCX, was inactivated, although the morphology of the cells was not affected. The importance of these genes in interneuron migration was confirmed by our finding that the cortices of Dcx, Dclk, and Dcx/Dclk mutant mice contained a reduced number of such cells in the cortex and their distribution was different compared with wild-type controls. However, the defect was different for each group of mutant animals, suggesting that DCX and DCLK have distinct roles in cortical interneuron migration