New nonlinear-laser effects in crystalline fine-grained ceramics based on cubic Sc2O3 and Lu2O3 oxides: second and third harmonic generation, and cascaded self-sum-frequency mixing in UV spectral region

We report on the first observation of the nonlinear cascading chi((3)) chi((3)) effects in UV spectral range and second harmonic generation stipulated by the "defect" nonlinearity under one-micron pumping in crystalline ceramics based on cubic oxides Sc2O3 and Lu2O3. Broadband their multi-wavelength Stokes and anti-Stokes combs with the extension of 10475 cm(-1) (for Sc2O3) and 8232 cm(-1) (for Lu2O3) were recorded as well

Targeted bisulfite sequencing by solution hybrid selection and massively parallel sequencing

We applied a solution hybrid selection approach to the enrichment of CpG islands (CGIs) and promoter sequences from the human genome for targeted high-throughput bisulfite sequencing. A single lane of Illumina sequences allowed accurate and quantitative analysis of ~1 million CpGs in more than 21 408 CGIs and more than 15 946 transcriptional regulatory regions. Of the CpGs analyzed, 77–84% fell on or near capture probe sequences; 69–75% fell within CGIs. More than 85% of capture probes successfully yielded quantitative DNA methylation information of targeted regions. Differentially methylated regions (DMRs) were identified in the 5′-end regulatory regions, as well as the intra- and intergenic regions, particularly in the X-chromosome among the three breast cancer cell lines analyzed. We chose 46 candidate loci (762 CpGs) for confirmation with PCR-based bisulfite sequencing and demonstrated excellent correlation between two data sets. Targeted bisulfite sequencing of three DNA methyltransferase (DNMT) knockout cell lines and the wild-type HCT116 colon cancer cell line revealed a significant decrease in CpG methylation for the DNMT1 knockout and DNMT1, 3B double knockout cell lines, but not in DNMT3B knockout cell line. We demonstrated the targeted bisulfite sequencing approach to be a powerful method to uncover novel aberrant methylation in the cancer epigenome. Since all targets were captured and sequenced as a pool through a series of single-tube reactions, this method can be easily scaled up to deal with a large number of samples

X-ray Astronomy in the Laboratory with a Miniature Compact Object Produced by Laser-Driven Implosion

Laboratory spectroscopy of non-thermal equilibrium plasmas photoionized by intense radiation is a key to understanding compact objects, such as black holes, based on astronomical observations. This paper describes an experiment to study photoionizing plasmas in laboratory under well-defined and genuine conditions. Photoionized plasma is here generated using a 0.5-keV Planckian x-ray source created by means of a laser-driven implosion. The measured x-ray spectrum from the photoionized silicon plasma resembles those observed from the binary stars Cygnus X-3 and Vela X-1 with the Chandra x-ray satellite. This demonstrates that an extreme radiation field was produced in the laboratory, however, the theoretical interpretation of the laboratory spectrum significantly contradicts the generally accepted explanations in x-ray astronomy. This model experiment offers a novel test bed for validation and verification of computational codes used in x-ray astronomy.Comment: 5 pages, 4 figures are included. This is the original submitted version of the manuscript to be published in Nature Physic

A Real-Time Contouring Feedback Tool for Consensus-Based Contour Training

PURPOSE: Variability in contouring structures of interest for radiotherapy continues to be challenging. Although training can reduce such variability, having radiation oncologists provide feedback can be impractical. We developed a contour training tool to provide real-time feedback to trainees, thereby reducing variability in contouring. METHODS: We developed a novel metric termed localized signed square distance (LSSD) to provide feedback to the trainee on how their contour compares with a reference contour, which is generated real-time by combining trainee contour and multiple expert radiation oncologist contours. Nine trainees performed contour training by using six randomly assigned training cases that included one test case of the heart and left ventricle (LV). The test case was repeated 30 days later to assess retention. The distribution of LSSD maps of the initial contour for the training cases was combined and compared with the distribution of LSSD maps of the final contours for all training cases. The difference in standard deviations from the initial to final LSSD maps, ΔLSSD, was computed both on a per-case basis and for the entire group. RESULTS: For every training case, statistically significant ΔLSSD were observed for both the heart and LV. When all initial and final LSSD maps were aggregated for the training cases, before training, the mean LSSD ([range], standard deviation) was -0.8 mm ([-37.9, 34.9], 4.2) and 0.3 mm ([-25.1, 32.7], 4.8) for heart and LV, respectively. These were reduced to -0.1 mm ([-16.2, 7.3], 0.8) and 0.1 mm ([-6.6, 8.3], 0.7) for the final LSSD maps during the contour training sessions. For the retention case, the initial and final LSSD maps of the retention case were aggregated and were -1.5 mm ([-22.9, 19.9], 3.4) and -0.2 mm ([-4.5, 1.5], 0.7) for the heart and 1.8 mm ([-16.7, 34.5], 5.1) and 0.2 mm ([-3.9, 1.6],0.7) for the LV. CONCLUSIONS: A tool that uses real-time contouring feedback was developed and successfully used for contour training of nine trainees. In all cases, the utility was able to guide the trainee and ultimately reduce the variability of the trainee\u27s contouring

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The Antioxidant Protein Peroxiredoxin 4 Is Epigenetically Down Regulated in Acute Promyelocytic Leukemia

The antioxidant peroxiredoxin (PRDX) protein family comprises 6 members, which are implicated in a variety of cellular responses, including growth factor signal transduction. PRDX4 resides in the endoplasmic reticulum (ER), where it locally controls oxidative stress by reducing H2O2levels. We recently provided evidence for a regulatory function of PRDX4 in signal transduction from a myeloid growth factor receptor, the granulocyte colony-stimulating factor receptor (G-CSFR). Upon activation, the ligand-induced G-CSFR undergoes endocytosis and routes via the early endosomes where it physically interacts with ER-resident PRDX4. PRDX4 negatively regulates G-CSFR mediated signaling. Here, we investigated whether PRDX4 is affected in acute myeloid leukemia (AML); genomic alterations and expression levels of PRDX4 were investigated. We show that genomic abnormalities involving PRDX4 are rare in AML. However, we find a strong reduction in PRDX4 expression levels in acute promyelocytic leukemia (APL) compared to normal promyelocytes and different molecular subtypes of AML. Subsequently, the possible role of DNA methylation and histone modifications in silencing of PRDX4 in APLs was investigated. We show that the reduced expression is not due to methylation of the CpG island in the promoter region of PRDX4 but correlates with increased trimethylation of histone 3 lysine residue 27 (H3K27me3) and lysine residue 4 (H3K4me3) at the transcriptional start site (TSS) of PRDX4, indicative of a bivalent histone code involved in transcriptional silencing. These findings suggest that the control of G-CSF responses by the antioxidant protein PRDX4 may be perturbed in APL

ATF3 Plays a Key Role in Kdo2-Lipid A-Induced TLR4-Dependent Gene Expression via NF-κB Activation

Background: Activating transcription factor 3 (ATF3) is a negative regulator of proinflammatory cytokine expression in macrophages, and ATF3 deficient mice are more susceptible to endotoxic shock. This study addresses the role of ATF3 in the Kdo 2-Lipid A-induced Toll-like receptor 4 (TLR4) signaling pathway in mouse embryonic fibroblasts (MEF). Kdo 2-Lipid A upregulates ATF3 expression in wild type MEF cells and induces both nuclear factor kappa B (NF-kB) and c-Jun N-terminal kinase (JNK) activation via the TLR4 signaling pathway, while neither of these pathways is activated in ATF3-/- MEF cells. Interestingly, in contrast to Kdo 2-Lipid A, the activation of both NF-kB and JNK by TNF-a was normal in ATF3-/- MEF cells. Methodology/Principal Findings: We found that several genes were dramatically upregulated in ATF3+/+ MEF cells in response to Kdo2-Lipid A treatment, while little difference was observed in the ATF3-/- MEF cells. However, we also found that the signal intensities of IkBf in ATF3-/- MEF cells were substantially higher than those in wild type MEF cells upon microarray analyses, and upregulated IkBf expression was detected in the cytosol fraction. Conclusions/Significance: Our findings indicate that ATF3 deficiency affects Kdo 2-Lipid A-induced TLR4 signaling pathways in MEF cells, that it may upregulate IkBf expression and that the high levels of IkBf expression in ATF3-/- cells disrupts Kdo2-Lipid A-mediated signaling pathways

FAST-ASKAP Synergy: Quantifying Coexistent Tidal and Ram-Pressure Strippings in the NGC 4636 Group

Combining new HI data from a synergetic survey of ASKAP WALLABY and FAST with the ALFALFA data, we study the effect of ram-pressure and tidal interactions in the NGC 4636 group. We develop two parameters to quantify and disentangle these two effects on gas stripping in HI-bearing galaxies: the strength of external forces at the optical-disk edge, and the outside-in extents of HI-disk stripping. We find that gas stripping is widespread in this group, affecting 80% of HI-detected non-merging galaxies, and that 34% are experiencing both types of stripping. Among the galaxies experiencing both effects, the strengths (and extents) of ram-pressure and tidal stripping are independent of each other. Both strengths are correlated with HI-disk shrinkage. The tidal strength is related to a rather uniform reddening of low-mass galaxies ($M_*<10^9\,\text{M}_\odot$) when tidal stripping is the dominating effect. In contrast, ram pressure is not clearly linked to the color-changing patterns of galaxies in the group. Combining these two stripping extents, we estimate the total stripping extent, and put forward an empirical model that can describe the decrease of HI richness as galaxies fall toward the group center. The stripping timescale we derived decreases with distance to the center, from $\mathord{\sim}1\,\text{Gyr}$ around $R_{200}$ to $\mathord{\lesssim}10\,\text{Myr}$ near the center. Gas-depletion happens $\mathord{\sim}3\,\text{Gyr}$ since crossing $2R_{200}$ for HI-rich galaxies, but much quicker for HI-poor ones. Our results quantify in a physically motivated way the details and processes of environmental-effects-driven galaxy evolution, and might assist in analyzing hydrodynamic simulations in an observational way.Comment: 44 pages, 22 figures, 5 tables, accepted for publication in ApJ. Tables 4 and 5 are also available in machine-readable for

Automated Contouring and Planning in Radiation Therapy: What Is \u27Clinically Acceptable\u27?

Developers and users of artificial-intelligence-based tools for automatic contouring and treatment planning in radiotherapy are expected to assess clinical acceptability of these tools. However, what is \u27clinical acceptability\u27? Quantitative and qualitative approaches have been used to assess this ill-defined concept, all of which have advantages and disadvantages or limitations. The approach chosen may depend on the goal of the study as well as on available resources. In this paper, we discuss various aspects of \u27clinical acceptability\u27 and how they can move us toward a standard for defining clinical acceptability of new autocontouring and planning tools