Unveiling the pathway to Z-DNA in the protein-induced B–Z transition

Left-handed Z-DNA is an extraordinary conformation of DNA, which can form by special sequences under specific biological, chemical or physical conditions. Human ADAR1, prototypic Z-DNA binding protein (ZBP), binds to Z-DNA with high affinity. Utilizing single-molecule FRET assays for Z-DNA forming sequences embedded in a long inactive DNA, we measure thermodynamic populations of ADAR1-bound DNA conformations in both GC and TG repeat sequences. Based on a statistical physics model, we determined quantitatively the affinities of ADAR1 to both Z-form and B-form of these sequences. We also reported what pathways it takes to induce the B–Z transition in those sequences. Due to the high junction energy, an intermediate B* state has to accumulate prior to the B–Z transition. Our study showing the stable B* state supports the active picture for the protein-induced B–Z transition that occurs under a physiological setting. (c)The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research

The Far-Infrared Surveyor (FIS) for AKARI

The Far-Infrared Surveyor (FIS) is one of two focal plane instruments on the AKARI satellite. FIS has four photometric bands at 65, 90, 140, and 160 um, and uses two kinds of array detectors. The FIS arrays and optics are designed to sweep the sky with high spatial resolution and redundancy. The actual scan width is more than eight arcmin, and the pixel pitch is matches the diffraction limit of the telescope. Derived point spread functions (PSFs) from observations of asteroids are similar to the optical model. Significant excesses, however, are clearly seen around tails of the PSFs, whose contributions are about 30% of the total power. All FIS functions are operating well in orbit, and its performance meets the laboratory characterizations, except for the two longer wavelength bands, which are not performing as well as characterized. Furthermore, the FIS has a spectroscopic capability using a Fourier transform spectrometer (FTS). Because the FTS takes advantage of the optics and detectors of the photometer, it can simultaneously make a spectral map. This paper summarizes the in-flight technical and operational performance of the FIS.Comment: 23 pages, 10 figures, and 2 tables. Accepted for publication in the AKARI special issue of the Publications of the Astronomical Society of Japa

Retrospective analyses of cisplatin-based doublet combination chemotherapy in patients with advanced gastric cancer

<p>Abstract</p> <p>Backgrounds</p> <p>Cisplatin-based chemotherapy, in combination with fluoropyrimidines or taxanes, have demonstrated efficacy against advanced gastric cancer (AGC). This retrospective study was performed with the data obtained from our cancer chemotherapy registry and eight another cancer centers.</p> <p>Methods</p> <p>In 2008, a total of 283 AGC patients were treated with cisplatin-based doublet chemotherapy in the first-line setting: capecitabine plus cisplatin (XP, n = 77), S-1 plus cisplatin (SP, n = 97), taxanes (docetaxel, paclitaxel) plus cisplatin (TP, n = 72), and 5-fluorouracil plus platinum (FP, n = 37). The primary endpoint of this study was overall survival (OS) and the secondary endpoints were safety, response rate and progression-free survival (PFS).</p> <p>Results</p> <p>The median age was 54 years with a range of 28-78 years and median delivered number of chemotherapy cycles were XP: 4, SP: 5, TP: 5 and FP: 5, respectively. Objective tumor responses (38%; 95% CI, 32-43%) were 40% for XP, 42% for SP, 36% for DP, and 24% for FP. The estimated median PFS was 4.5 months (95% CI, 3.6-5.4 months) and the median OS was 12.3 months (95% CI, 10.8-13.7 months). No statistically significant difference was found between each regimen used as first-line chemotherapy. At multivariate analysis, independent prognostic parameters for OS were prior gastrectomy, peritoneal dissemination, performance status and hemoglobin level</p> <p>Conclusion</p> <p>All of the cisplatin-based doublet chemotherapy regimens appear to be active as first-line chemotherapy for AGC. With better patient selection according to clinical parameters and molecular markers, clinical outcomes of AGC patients in first-line setting can be improved.</p

Glioma Through the Looking GLASS: Molecular Evolution of Diffuse Gliomas and the Glioma Longitudinal AnalySiS Consortium

Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas (TCGA) and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal AnalySiS Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities, and ultimately, improved outcomes for a patient population in need

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Liquid crystal clad near-infrared metamaterials with tunable negative-zero-positive refractive indices

Near-infrared metamaterials that possess a reconfigurable index of refraction from negative through zero to positive values are presented. Reconfigurability is achieved by cladding thin layers of liquid crystal both as a superstrate and a substrate on an established negative-index metamaterial, and adjusting the permittivity of the liquid crystal. Numerical results show that the index of refraction for the proposed structure can be changed over the range from -1 to +1.8 by tuning the liquid crystal permittivity from 2 to 6 at a wavelength of 1.4 mu m

Tunable optical negative-index metamaterials employing anisotropic liquid crystals

A full-wave analysis technique based on the finite element-boundary integral method is developed and used to rigorously treat the scattering from periodically structured metamaterials incorporating anisotropic liquid crystals (LCs) and dispersive materials. Reconfiguration of the negative-index metamaterials is achieved by controlling the magnetic resonance via tuning permittivity of the embedded anisotropic LCs. Numerical results show that the refractive index of the metamaterials can be reconfigured by tuning the director orientation of anisotropic LCs or by using temperature-dependent LCs. The design configurations and their characteristics in the near- and the mid-infrared ranges are presented

Magnetic properties of natural and modified DNAs

info:eu-repo/semantics/publishe

Majorana fermions in the Kitaev quantum spin system alpha-RuCl3

Geometrical constraints to the electronic degrees of freedom within condensed-matter systems often give rise to topological quantum states of matter such as fractional quantum Hall states, topological insulators, and Weyl semimetals(1-3). In magnetism, theoretical studies predict an entangled magnetic quantum state with topological ordering and fractionalized spin excitations, the quantum spin liquid(4). In particular, the so-called Kitaev spin model(5), consisting of a network of spins on a honeycomb lattice, is predicted to host Majorana fermions as its excitations. By means of a combination of specific heat measurements and inelastic neutron scattering experiments, we demonstrate the emergence of Majorana fermions in single crystals of alpha-RuCl3, an experimental realization of the Kitaev spin lattice. The specific heat data unveils a two-stage release of magnetic entropy that is characteristic of localized and itinerant Majorana fermions. The neutron scattering results corroborate this picture by revealing quasielastic excitations at low energies around the Brillouin zone centre and an hour-glass-like magnetic continuum at high energies. Our results confirm the presence of Majorana fermions in the Kitaev quantum spin liquid and provide an opportunity to build a unified conceptual framework for investigating fractionalized excitations in condensed matter(1,6-8).1133Ysciescopu