350 Micron Dust Emission from High Redshift Objects

We report observations of a sample of high redshift sources (1.8<z<4.7), mainly radio-quiet quasars, at 350 microns using the SHARC bolometer camera at the Caltech Submillimeter Observatory. Nine sources were detected (>4-sigma) and upper limits were obtained for 11 with 350 micron flux density limits (3-sigma) in the range 30-125mJy. Combining published results at other far-infrared and millimeter wavelengths with the present data, we are able to estimate the temperature of the dust, finding relatively low values, averaging 50K. From the spectral energy distribution, we derive dust masses of a few 10^8 M_sun and luminosities of 4-33x10^{12} L_sun (uncorrected for any magnification) implying substantial star formation activity. Thus both the temperature and dust masses are not very different from those of local ultraluminous infrared galaxies. For this redshift range, the 350 micron observations trace the 60-100 micron rest frame emission and are thus directly comparable with IRAS studies of low redshift galaxies.Comment: 5 pages, 2 PS figures. Accepted for publication in Astrophysical Journal Letter

Protein Kinase C Delta (PKCδ) Affects Proliferation of Insulin-Secreting Cells by Promoting Nuclear Extrusion of the Cell Cycle Inhibitor p21Cip1/WAF1

BACKGROUND:High fat diet-induced hyperglycemia and palmitate-stimulated apoptosis was prevented by specific inhibition of protein kinase C delta (PKCδ) in β-cells. To understand the role of PKCδ in more detail the impact of changes in PKCδ activity on proliferation and survival of insulin-secreting cells was analyzed under stress-free conditions. METHODOLOGY AND PRINCIPAL FINDINGS:Using genetic and pharmacological approaches, the effect of reduced and increased PKCδ activity on proliferation, apoptosis and cell cycle regulation of insulin secreting cells was examined. Proteins were analyzed by Western blotting and by confocal laser scanning microscopy. Increased expression of wild type PKCδ (PKCδWT) significantly stimulated proliferation of INS-1E cells with concomitant reduced expression and cytosolic retraction of the cell cycle inhibitor p21(Cip1/WAF1). This nuclear extrusion was mediated by PKCδ-dependent phosphorylation of p21(Cip1/WAF1) at Ser146. In kinase dead PKCδ (PKCδKN) overexpressing cells and after inhibition of endogenous PKCδ activity by rottlerin or RNA interference phosphorylation of p21(Cip1/WAF1) was reduced, which favored its nuclear accumulation and apoptotic cell death of INS-1E cells. Human and mouse islet cells express p21(Cip1/WAF1) with strong nuclear accumulation, while in islet cells of PKCδWT transgenic mice the inhibitor resides cytosolic. CONCLUSIONS AND SIGNIFICANCE:These observations disclose PKCδ as negative regulator of p21(Cip1/WAF1), which facilitates proliferation of insulin secreting cells under stress-free conditions and suggest that additional stress-induced changes push PKCδ into its known pro-apoptotic role

High Glutathione and Glutathione Peroxidase-2 Levels Mediate Cell-Type-Specific DNA Damage Protection in Human Induced Pluripotent Stem Cells

Pluripotent stem cells must strictly maintain genomic integrity to prevent transmission of mutations. In human induced pluripotent stem cells (iPSCs), we found that genome surveillance is achieved via two ways, namely, a hypersensitivity to apoptosis and a very low accumulation of DNA lesions. The low apoptosis threshold was mediated by constitutive p53 expression and a marked upregulation of proapoptotic p53 target genes of the BCL-2 family, ensuring the efficient iPSC removal upon genotoxic insults. Intriguingly, despite the elevated apoptosis sensitivity, both mitochondrial and nuclear DNA lesions induced by genotoxins were less frequent in iPSCs compared to fibroblasts. Gene profiling identified that mRNA expression of several antioxidant proteins was considerably upregulated in iPSCs. Knockdown of glutathione peroxidase-2 and depletion of glutathione impaired protection against DNA lesions. Thus, iPSCs ensure genomic integrity through enhanced apoptosis induction and increased antioxidant defense, contributing to protection against DNA damage

Spatial organization of the mouse genome and its role in recurrent chromosomal translocations

The extent to which the three-dimensional organization of the genome contributes to chromosomal translocations is an important question in cancer genomics. We generated a high-resolution Hi-C spatial organization map of the G1-arrested mouse pro-B cell genome and used high-throughput genome-wide translocation sequencing to map translocations from target DNA double-strand breaks (DSBs) within it. RAG endonuclease-cleaved antigen-receptor loci are dominant translocation partners for target DSBs regardless of genomic position, reflecting high-frequency DSBs at these loci and their colocalization in a fraction of cells. To directly assess spatial proximity contributions, we normalized genomic DSBs via ionizing radiation. Under these conditions, translocations were highly enriched in cis along single chromosomes containing target DSBs and within other chromosomes and subchromosomal domains in a manner directly related to pre-existing spatial proximity. By combining two high-throughput genomic methods in a genetically tractable system, we provide a new lens for viewing cancer genomes

Rapid variability of Markarian 421 during extreme flaring as seen through the eyes of XMM-Newton

By studying the variability of blazars across the electromagnetic spectrum, it is possible to resolve the underlying processes responsible for rapid flux increases, so-called flares. We report on an extremely bright X-ray flare in the high-peaked BL Lacertae object Markarian 421 (Mrk 421) that occurred simultaneously with enhanced γ-ray activity detected at very high energies by First G-APD Cherenkov Telescope on 2019 June 9. We triggered an observation with XMM-Newton, which observed the source quasi-continuously for 25 h. We find that the source was in the brightest state ever observed using XMM-Newton, reaching a flux of 2.8 × 10-9 over an energy range of 0.3-10 keV. We perform a spectral and timing analysis to reveal the mechanisms of particle acceleration and to search for the shortest source-intrinsic time-scales. Mrk 421 exhibits the typical harder-when-brighter behaviour throughout the observation and shows a clock-wise hysteresis pattern, which indicates that the cooling dominates over the acceleration process. While the X-ray emission in different sub-bands is highly correlated, we can exclude large time lags as the computed z-transformed discrete correlation functions are consistent with a zero lag. We find rapid variability on time-scales of 1 ks for the 0.3-10 keV band and down to 300 s in the hard X-ray band (4-10 keV). Taking these time-scales into account, we discuss different models to explain the observed X-ray flare, and find that a plasmoid-dominated magnetic reconnection process is able to describe our observation best.ISSN:0035-8711ISSN:1365-296

Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 7