Detection of the Far-infrared [O III] and Dust Emission in a Galaxy at Redshift 8.312: Early Metal Enrichment in the Heart of the Reionization Era

We present the Atacama Large Millimeter/submillimeter Array (ALMA) detection of the [O III] 88 $\mu$m line and rest-frame 90 $\mu$m dust continuum emission in a Y-dropout Lyman break galaxy (LBG), MACS0416_Y1, lying behind the Frontier Field cluster MACS J0416.1-2403. This [O III] detection confirms the LBG with a spectroscopic redshift of $z = 8.3118 \pm 0.0003$, making this object one of the furthest galaxies ever identified spectroscopically. The observed 850 $\mu$m flux density of $137 \pm 26$ $\mu$Jy corresponds to a de-lensed total infrared (IR) luminosity of $L_{\rm IR} = (1.7 \pm 0.3) \times 10^{11} L_{\odot}$ if assuming a dust temperature of $T_{\rm dust} = 50$ K and an emissivity index of $\beta = 1.5$, yielding a large dust mass of $4 \times 10^6 M_{\odot}$. The ultraviolet-to-far IR spectral energy distribution modeling where the [O III] emissivity model is incorporated suggests the presence of a young ($\tau_{\rm age} \approx 4$ Myr), star-forming (SFR $\approx 60 M_{\odot}$ yr$^{-1}$), moderately metal-polluted ($Z \approx 0.2 Z_{\odot}$) stellar component with a mass of $M_{\rm star} = 3 \times 10^8 M_{\odot}$. An analytic dust mass evolution model with a single episode of star-formation does not reproduce the metallicity and dust mass in $\tau_{\rm age} \approx 4$ Myr, suggesting a pre-existing evolved stellar component with $M_{\rm star} \sim 3 \times 10^9 M_{\odot}$ and $\tau_{\rm age} \sim 0.3$ Gyr as the origin of the dust mass.Comment: Accepted by ApJ. 18 pages, 10 figures, 5 table

Perturbation study on the spin and charge susceptibilities of the two-dimensional Hubbard model

We investigate the spin and charge susceptibilities of the two-dimensional Hubbard model based upon the perturbative calculation in the strength of correlation $U$. For $U$ comparable to a bare bandwidth, the charge susceptibility decreases near the half-filling as hole-doping approaches zero. This behavior suggesting the precursor of the Mott-Hubbard gap formation cannot be obtained without the vertex corrections beyond the random phase approximation. In the low-temperature region, the spin susceptibility deviates from the Curie-Weiss-like law and finally turns to decrease with the decrease of temperature. This spin-gap-like behavior is originating from the van Hove singularity in the density of states.Comment: Revtex file + 11 figures, to appear in Phys. Rev.

A gene-alteration profile of human lung cancer cell lines

ABSTRACT: Aberrant proteins encoded from genes altered in tumors drive cancer development and may also be therapeutic targets. Here we derived a comprehensive gene-alteration profile of lung cancer cell lines. We tested 17 genes in a panel of 88 lung cancer cell lines and found the rates of alteration to be higher than previously thought. Nearly all cells feature inactivation at TP53 and CDKN2A or RB1, whereas BRAF, MET, ERBB2, and NRAS alterations were infrequent. A preferential accumulation of alterations among histopathological types and a mutually exclusive occurrence of alterations of CDKN2A and RB1 as well as of KRAS, epidermal growth factor receptor (EGFR), NRAS, and ERBB2 were seen. Moreover, in nonsmall- cell lung cancer (NSCLC), concomitant activation of signal transduction pathways known to converge in mammalian target of rapamycin (mTOR) was common. Cells with single activation of ERBB2, PTEN, or MET signaling showed greater sensitivity to cell-growth inhibition induced by erlotinib, LY294002, and PHA665752, respectively, than did cells featuring simultaneous activation of these pathways, underlining the need for combined therapeutic strategies in targeted cancer treatments. In conclusion, our gene-alteration landscape of lung cancer cell lines provides insights into how gene alterations accumulate and biological pathways interact in cancer. Hum Mutat 30, 1199–1206, 2009. & 2009Wiley-Liss, Inc

A Conditional Deletion of the NR1 Subunit of the NMDA Receptor in Adult Spinal Cord Dorsal Horn Reduces NMDA Currents and Injury-Induced Pain

To determine the importance of the NMDA receptor (NMDAR) in pain hypersensitivity after injury, the NMDAR1 (NR1) subunit was selectively deleted in the lumbar spinal cord of adult mice by the localized injection of an adenoassociated virus expressing Cre recombinase into floxed NR1 mice. NR1 subunit mRNA and dendritic protein are reduced by 80% in the area of the virus injection, and NMDA currents, but not AMPA currents, are reduced 86–88% in lamina II neurons. The spatial NR1 knock-out does not alter heat or cold paw-withdrawal latencies, mechanical threshold, or motor function. However, injury-induced pain produced by intraplantar formalin is reduced by 70%. Our results demonstrate conclusively that the postsynaptic NR1 receptor subunit in the lumbar dorsal horn of the spinal cord is required for central sensitization, the central facilitation of pain transmission produced by peripheral injury

Essential Factors for Incompatible DNA End Joining at Chromosomal DNA Double Strand Breaks In Vivo

Non-homologous end joining (NHEJ) is a major pathway for the repair of DNA double strand break (DSBs) with incompatible DNA ends, which are often generated by ionizing irradiation. In vitro reconstitution studies have indicated that NHEJ of incompatible DNA ends requires not only the core steps of synapsis and ligation, employing KU80/DNA-PKcs and LIG4, but also additional DNA end processing steps, such as DNA end resection by Artemis and gap-filling by POLλ and POLμ. It seems that DNA end processing steps are important for joining of incompatible DNA ends rather than compatible ends. Despite the fact that DNA end processing is important for incompatible DNA end joining in vitro, the role of DNA processing in NHEJ of incompatible DSBs in vivo has not yet been demonstrated. Here we investigated the in vivo roles of proteins implicated in each step of NHEJ using an assay in which NHEJ of incompatible DNA ends on chromosomal DNA can be assessed in living human cells. siRNA- or inhibitor-mediated impairment of factors in each NHEJ step resulted in a reduction in joining efficiency. Strikingly, stronger effects were observed when DNA end resection and ligation protein functions were impaired. Disruption of synapsis by KU80 and DNA-PKcs impairment, or the disruption of gap filling by POLλ and POLμ depletion, resulted in higher levels of microhomology-mediated joining. The present study indicates that DNA end resection and ligation factors are critical for the efficient joining of incompatible ends in vivo, further emphasizing the importance of synapsis and gap-filling factors in preventing illegitimate joining

Percutaneous Cryoablation for the Treatment of Medically Inoperable Stage I Non-Small Cell Lung Cancer

BACKGROUND: To evaluate the midterm results of percutaneous cryoablation for medically inoperable stage I non-small cell lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Between January 2004 and June 2010, 160 patients underwent computer tomography guided percutaneous cryoablation for lung tumors at our institution. Of these patients, histologically proven stage I lung cancer patients with more than one year of follow-up, were retrospectively reviewed. All of these patients were considered to be medically inoperable with Charlson comorbidity index of 3 or greater. Follow-up was based primarily on computed tomography. There were 22 patients with 34 tumors who underwent 25 sessions of cryoablation treatment. Complications were pneumothoraces in 7 treatments (28%, chest tube required in one treatment), and pleural effusions in 8 treatments (31%). The observation period ranged from 12-68 months, average 29±19 months, median 23 months. Local tumor progression was observed in one tumor (3%). Mean local tumor progression-free interval was 69±2 months. One patient died of lung cancer progression at 68 months. Two patients died of acute exacerbations of idiopathic pulmonary fibrosis which were not considered to be directly associated with cryoablation, at 12 and 18 months, respectively. The overall 2- and 3-year survivals were 88% and 88%, respectively. Mean overall survival was 62±4 months. Median overall survival was 68 months. The disease-free 2- and 3-year survivals were 78% and 67%, respectively. Mean disease-free survival was 46±6 months. Pulmonary function tests were done in 16 patients (18 treatments) before and after cryoablation. Percentage of predicted vital capacity, and percentage of predicted forced expiratory volume in 1 second, did not differ significantly before and after cryoablation (93±23 versus 90±21, and 70±11 versus 70±12, respectively). CONCLUSIONS/SIGNIFICANCE: Although further accumulation of data is necessary regarding efficacy, cryoablation may be a feasible option in medically inoperable stage I lung cancer patients

Circadian Disruption Accelerates Tumor Growth and Angio/Stromagenesis through a Wnt Signaling Pathway

Epidemiologic studies show a high incidence of cancer in shift workers, suggesting a possible relationship between circadian rhythms and tumorigenesis. However, the precise molecular mechanism played by circadian rhythms in tumor progression is not known. To identify the possible mechanisms underlying tumor progression related to circadian rhythms, we set up nude mouse xenograft models. HeLa cells were injected in nude mice and nude mice were moved to two different cases, one case is exposed to a 24-hour light cycle (L/L), the other is a more “normal” 12-hour light/dark cycle (L/D). We found a significant increase in tumor volume in the L/L group compared with the L/D group. In addition, tumor microvessels and stroma were strongly increased in L/L mice. Although there was a hypervascularization in L/L tumors, there was no associated increase in the production of vascular endothelial cell growth factor (VEGF). DNA microarray analysis showed enhanced expression of WNT10A, and our subsequent study revealed that WNT10A stimulates the growth of both microvascular endothelial cells and fibroblasts in tumors from light-stressed mice, along with marked increases in angio/stromagenesis. Only the tumor stroma stained positive for WNT10A and WNT10A is also highly expressed in keloid dermal fibroblasts but not in normal dermal fibroblasts indicated that WNT10A may be a novel angio/stromagenic growth factor. These findings suggest that circadian disruption induces the progression of malignant tumors via a Wnt signaling pathway

Paradoxical expression of IL-28B mRNA in peripheral blood in human T-cell leukemia virus Type-1 mono-infection and co-infection with hepatitis C Virus

<p>Abstract</p> <p>Background</p> <p>Human T-cell leukemia virus type-1 (HTLV-1) carriers co-infected with and hepatitis C virus (HCV) have been known to be at higher risk of their related diseases than mono-infected individuals. The recent studies clarified that IL-28B polymorphism rs8099917 is associated with not only the HCV therapeutic response by IFN, but also innate immunity and antiviral activity. The aim of our research was to clarify study whether IL-28B gene polymorphism (rs8099917) is associated with HTLV-1/HCV co-infection.</p> <p>Results</p> <p>The genotyping and viral-serological analysis for 340 individuals showed that IL-28B genotype distribution of rs8099917 SNP did not differ significantly by respective viral infection status. However, the IL-28B mRNA expression level was 3.8 fold higher in HTLV-1 mono-infection than HTLV-1/HCV co-infection. The high expression level was associated with TT (OR, 6.25), whiles the low expression was associated with co-infection of the two viruses (OR, 9.5). However, there was no association between down-regulation and ATL development (OR, 0.8).</p> <p>Conclusion</p> <p>HTLV-1 mono-infection up-regulates the expression of IL-28B transcripts in genotype-dependent manner, whiles HTLV-1/HCV co-infection down-regulates regardless of ATL development.</p

Safety of Postoperative Administration of Human Urinary Trypsin Inhibitor in Lung Cancer Patients with Idiopathic Pulmonary Fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) undergoing pulmonary resection for lung cancer carry risks of acute exacerbations of IPF (AE) postoperatively. Currently, agents which may attenuate AE are actively sought. Urinary trypsin inhibitor, ulinastatin, is a synthetic glycoprotein which may potentially inhibit various inflammatory factors associated with the development and progression of IPF. The present study was done to evaluate the effects of administration of high dose ulinastatin in lung cancer patients with IPF immediately following lung resection.Patients with IPFs radiologically diagnosed on high resolution CT, and histologically diagnosed resectable lung cancers, were eligible for the study. The effects of escalating doses of ulinastatin 3×10(5), 6×10(5), and 9×10(5) units/body/day, administered postoperatively for 3 days were evaluated. The endpoints were safety and feasibility.Nine patients were evaluated, in cohorts of 3 patients per dosage. Postoperative follow up ranged from 3 to 12 months (median 9 months). The postoperative courses were uneventful in all patients. No subjective adverse events such as abdominal symptoms or skin rashes, or objective adverse events as per serum laboratory tests, such as liver or kidney dysfunctions potentially attributable to ulinastatin administration were observed. AE was seen in one patient at 3 months after surgery, but since this occurred shortly after administration of chemotherapy, it was considered to be attributable to the chemotherapy rather than surgery.Ulinastatin administration after lung resection in lung cancer patients with IPF was considered to be safe and feasible. Further study is planned at the highest dose of this study to evaluate efficacy.UMIN.ac.jp/ctr/UMIN000002410