Advanced Microscopic Evaluation of Parallel Type I and Type II Cell deaths Induced by Multi-functionalized Gold Nanocages in Breast Cancer

Despite aggressive surgical resections and combinatorial chemoradiations, certain highly malignant populations of tumor cells resurrect and metastasize. Mixed-grade cancer cells fail to respond to standard-of-care therapies by developing intrinsic chemoresistance and subsequently result in tumor relapse. Macroautophagy is a membrane trafficking process that underlies drug resistance and tumorigenesis in most breast cancers. Manipulating cellular homeostasis by a combinatorial nanotherapeutic model, one can evaluate the crosstalk between type I and type II cell death and decipher the fate of cancer therapy. Here, we present a multi-strategic approach in cancer targeting to mitigate the autophagic flux with subcellular toxicity via lysosome permeation, accompanied by mitochondrial perturbation and apoptosis. In this way, a nanoformulation is developed with a unique blend of a lysosomotropic agent, an immunomodulating sulfated-polysaccharide, an adjuvant chemotherapeutic agent, and a monoclonal antibody as a broad-spectrum complex for combinatorial nanotherapy of all breast cancers. To the best of our knowledge, this manuscript illustrates for the first time the applications of advanced microscopic techniques such as electron tomography, three-dimensional rendering and segmentation of subcellular interactions, and fate of the multifunctional therapeutic gold nanocages specifically targeted toward breast cancer cells

Thermomechanical surface instability at the origin of surface fissure patterns on heated circular MDF samples

When a flat sample of medium density fibreboard (MDF) is exposed to radiant heat in an inert atmosphere, primary crack patterns suddenly start to appear over the entire surface before pyrolysis and any charring occurs. Contrary to common belief that crack formation is due to drying and shrinkage, it was demonstrated for square samples that this results from thermomechanical instability. In the present paper, new experimental data are presented for circular samples of the same MDF material. The sample was exposed to radiant heating at 20 or 50 kW/m2, and completely different crack patterns with independent Eigenmodes were observed at the two heat fluxes. We show that the two patterns can be reproduced with a full 3-D thermomechanical surface instability model of a hot layer adhered to an elastic colder foundation in an axisymmetric domain. Analytical and numerical solutions of a simplified 2-D formulation of the same problem provide excellent qualitative agreement between observed and calculated patterns. Previous data for square samples together with the results reported in the present paper for circular samples confirm the validity of the model for qualitative predictions, and indicate that further refinements can be made to improve its quantitative predictive capability.Comment: 9 pages, 13 figures. New title and abstract, added experimental and simulation details and figures, conclusions unchanged. Matches the version published in Fire And Material

Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana

We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is ~32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

Progress of long pulse discharges by ECH in LHD

Using ion cyclotron heating and electron cyclotron heating (ECH), or solo ECH, trials of steady state plasma sustainment have been conducted in the superconducting helical/stellarator, large helical device (LHD) (Ida K et al 2015 Nucl. Fusion 55 104018). In recent years, the ECH system has been upgraded by applying newly developed 77 and 154 GHz gyrotrons. A new gas fueling system applied to the steady state operations in the LHD realized precise feedback control of the line average electron density even when the wall condition varied during long pulse discharges. Owing to these improvements in the ECH and the gas fueling systems, a stable 39 min discharge with a line average electron density ne_ave of 1.1  ×  1019 m−3, a central electron temperature Te0 of over 2.5 keV, and a central ion temperature Ti0 of 1.0 keV was successfully performed with ~350 kW EC-waves. The parameters are much improved from the previous 65 min discharge with ne_ave of 0.15  ×  1019 m−3 and Te0 of 1.7 keV, and the 30 min discharge with ne_ave of 0.7  ×  1019 m−3 and Te0 of 1.7 keV

Stable sustainment of plasmas with electron internal transport barrier by ECH in the LHD

The long pulse experiments in the Large Helical Device has made progress in sustainment of improved confinement states. It was found that steady-state sustainment of the plasmas with improved confinement at the core region, that is, electron internal transport barrier (e-ITB), was achieved with no significant difficulty. Sustainment of a plasma having e-ITB with the line average electron density ne_ave of 1.1 × 1019 m−3 and the central electron temperature Te0 of ∼3.5 keV for longer than 5 min only with 340 kW ECH power was successfully demonstrated