SDSS J0806+2006 and SDSS J1353+1138: Two New Gravitationally Lensed Quasars from the Sloan Digital Sky Survey

We report the discoveries of two, two-image gravitationally lensed quasars selected from the Sloan Digital Sky Survey: SDSS J0806+2006 at z_s=1.540 and SDSS J1353+1138 at z_s=1.629 with image separations of 1.40" and 1.41" respectively. Spectroscopic and optical/near-infrared imaging follow-up observations show that the quasar images have identical redshifts and possess extended objects between the images that are likely to be lens galaxies at z_l~0.6 in SDSS J0806+2006 and z_l~0.3 in SDSS J1353+1138. The field of SDSS J0806+2006 contains several nearby galaxies that may significantly perturb the system, and SDSS J1353+1138 has an extra component near its Einstein ring that is probably a foreground star. Simple mass models with reasonable parameters reproduce the quasar positions and fluxes of both systems.Comment: 27 pages, 7 figures, The Astronomical Journal accepte

Influence of atrial fibrillation on oxygen uptake and exercise tolerance in cardiovascular patients; close association with heart rate response

To investigate the effect of atrial fibrillation (AF) on the oxygen uptake and exercise tolerance, we evaluated cardiopulmonary exercise test (CPET) data in AF patients and heart rate-matched controls with sinus rhythm (cSR) who received ambulatory cardiac rehabilitation. We compared CPET data between AF (N = 27) and cSR patients (N = 106) who had similar HRs at rest and the peak points. Oxygen uptake (VO2)/kg and relative O2 pulse (ml/bpm/kg) at rest and the anaerobic threshold (AT) level was not different between AF and cSR patients, but these parameters above the AT level were significantly lower in AF than in cSR patients. Concisely the parallel increase of relative O2 pulse during exercise was blunted above the respiratory compensation level (Rc) in the AF group. In addition, the HR change during exercise was inversely correlated with the increase of the O2 pulse above the AT level and this inverse correlation was more prominent in AF patients than in cSR patients. In conclusion, the value of VO2 was significantly lower above the AT level in AF patients. The trend of O2 pulse above the AT level was strongly associated with the detrimental response of HR increase and the response was markedly exaggerated in the AF patients. Keywords: Atrial fibrillation, Oxygen uptake, O2 pulse, Heart rate response, Hemodynamic tren

ALK signaling cascade confers multiple advantages to glioblastoma cells through neovascularization and cell proliferation

<div><p>Anaplastic lymphoma kinase (ALK), which is a receptor tyrosine kinase, is essentially and transiently expressed in the developing nervous system. Here we examined the functional role of the <i>ALK</i> gene in glioblastomas (GBMs). In clinical samples of GBMs, high ALK expression without gene rearrangements or mutations was frequently observed in perivascular lesions, in contrast to the relatively low expression in the perinecrotic areas, which was positively correlated with N-myc and phosphorylated (p) Stat3 scores and Ki-67 labeling indices. ALK immunoreactivity was also found to be associated with neovascular features including vascular co-option and vascular mimicry. In astrocytoma cell lines, cells stably overexpressing full-length ALK showed an increase in expression of pStat3 and pAkt proteins, as well as hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) mRNAs, in contrast to cells with knockdown of endogenous ALK which showed decreased expression of these molecules. Transfection of the constitutively active form of Stat3 induced an increase in <i>HIF-1</i>α promoter activity, and the overexpression of HIF-1α in turn resulted in enhancement of <i>VEGF-A</i> promoter activity. In addition, cells with overexpression or knockdown of ALK also showed a tendency toward increased and decreased proliferation, respectively, through changes in expression of pAkt and pStat3. Finally, <i>ALK</i> promoter was significantly activated by transfection of Sox4 and N-myc, which are known to contribute to neuronal properties. These findings therefore suggest that N-myc/Sox4-mediated ALK signaling cascades containing Stat3, Akt, HIF-1α, and VEGF-A confer multiple advantages to tumor growth through alterations in neovascularization and cell proliferation in GBMs.</p></div

Association between ALK expression and cell proliferation in astrocytoma cells.

<p>(A) Left: KS-ALK#4 cells and mock cells were seeded at low density. The cell numbers are presented as means±SDs. P0, P2, P4, P6, and P8 indicate 0, 2, 4, 6, and 8 days after cell passage, respectively. Right: Cell Counting Kit-8 (CCK-8) assay for cell proliferation. Cells were seeded at 1x10³ cells in 96-well plates. Viable cell numbers were quantitated. Relative absorbance values (P5 or P7 relative to P2) are presented as means±SDs. P2, P5, and P7 indicate 2, 5, and 7 days after cell passage, respectively. This experiment was performed in triplicate using independent samples. (B) Western blot analysis for the indicated proteins in ALK#4 and mock cells after serum stimulation for the times shown. (C) Left: KINGS-shALK#37, #46 cells, and mock cells were seeded at low density. The cell numbers are presented as means±SDs. P0, P3, P6, and P9 indicate 0, 3, 6, and 9 days after cell passage, respectively. Right: CCK-8 assay for cell proliferation to quantitate viable cell numbers as mentioned above. (E) Staining by hematoxylin and eosin (HE) and IHC for pStat3, pAkt, and Ki-67 in GBMs. Note the strong immunoreactivity for these molecules in perivascular lesions (vessels are indicated by arrows), in contrast to the weak immunoreaction in perinecrotic areas (necrotic lesion is partitioned by dotted line). Original magnification, x100. (F) IHC scores for pStat3 and pAkt and Ki-67 labeling indices in perivascular (Pv) and perinecrotic (Pn) lesions.</p

ALK mRNA expression and gene arrangement status in GBMs.

<p>(A) Staining by hematoxylin and eosin (HE) and ISH for ALK mRNA. Note the abundant mRNA signals in tumor cells around vascular components (indicated by arrows), in contrast to the weak signals adjacent to necrotic foci (partitioned by dotted line). Insets show magnified views of the boxed areas. Original magnification, x100 and x400 (inset). (B) Relationship of ALK (5A4) expression between the ISH signal positivity and the IHC score in GBMs. (C) FISH analysis of four GMB cases with high ALK expression. The interphase nuclei of these cases indicate absence of ALK rearrangement, as shown by the merged red and green signals (indicated by arrows).</p

Correlations among IHC markers investigated in GBM cases.

<p>Correlations among IHC markers investigated in GBM cases.</p

Up-regulation of ALK expression in hypervascular areas of GBMs.

<p>(A) Left: staining by hematoxylin and eosin (HE) and IHC for ALK in GBMs. Note the strong cytoplasmic ALK (5A4) positivity in cells around vascular components (a) (indicated by arrows) of GBMs, in contrast to the sporadic staining or absence in tumor cells adjacent to necrotic foci (b) (partitioned by dotted line). Panels (a) and (b) are magnified views of the boxed areas. Original magnification, x100 (left) and x200 (middle and right). Right: IHC score for ALK (5A4) in perivascular (Peri-v) and perinecrotic (Peri-n) areas. (B) Staining by HE (upper and lower left) and double-staining for ALK/CD34 (upper and lower middle) and SMA/CD34 (upper and lower right) in mature vessels (upper) and microvessels (lower) in GBM. Strong ALK (5A4) (brown) positivity is observed in GBM cells surrounding CD34 (red)-positive mature vessels (upper middle), while focal ALK (5A4) immunoreactivity is also evident in CD34-positive microvessels (lower middle). Note the close association between SMA- and CD34-positive cells in both tumor vasculatures (upper and lower left). Insets show magnified views of the boxed areas. Original magnification, x200 and x400 (inset). (C) Left: staining by HE and IHC for ALK and CD34 in GBMs. Note the strong ALK (5A4) immunopositivity in areas with high CD34 immunoreactivity, in contrast to the sporadic staining or absence in the low immunoreactivity lesions. Original magnification, x100. Right: relationship between ALK (5A4) immunointensity and microvascular density as determined by CD34 immunoreactivity in GBMs. The data shown are means±SDs. (D) Western blot analysis of the indicated proteins after CoCl₂ treatment with the different doses shown for 24 hours (left) and 50 μM CoCl₂ for the time shown (right) in KINGS-1 cells.</p

ALK/Stat3/HIF-1α axis in astrocytoma cells.

<p>Western blot (left) and RT-PCR (right) analyses for the indicated molecules in (A) KS-ALK#4 cells and (B) KINGS-shALK#37 and #46 cells. (C) KS-1 cells were transfected with HIF-1α (left) and VEGF-A (right) reporter constructs, together with either ALK, Stat3C, or HIF-1α. Relative activity was determined based on arbitrary light units of luciferase activity normalized to pRL-TK activity. The activities of the reporter plus the effector relative to that of the reporter plus empty vector are shown as means±SDs. The experiment was performed in duplicate. v, empty vector. Western blot (left) and RT-PCR (right) analyses for the indicated molecules in (D) KS-ALK#4 cells and (E) KINGS-shALK#37 and #46 cells after CoCl₂ treatment for 4 hours. (F) Left: staining by hematoxylin and eosin (HE) and IHC for HIF-1α in GBMs. Note the strong HIF-1α immunoreactivity (indicated by arrows) in both perivascular areas and pseudopalisading around necrotic lesion (partitioned by dotted line). Original magnification, x100. Right: IHC score for HIF-1α in perivascular (Peri-v) and perinecrotic (Peri-n) areas of GBMs.</p

Association between ALK expression and neovascular features in GBMs.

<p>(A) Staining by hematoxylin and eosin (HE) and IHC for ALK in vascular co-option. Note the strong ALK (5A4) immunoreactivity in vascular co-option with classic perivascular cuffs (indicated by arrows). Insets show magnified view of the boxed area. Original magnification, x200 and x400 (inset). (B) Staining by HE and IHC for ALK and CD34 in vascular mimicry. Note the diffuse ALK (5A4) immunoreaction and focal CD34 immunoreactivity in the perfused vascular networks containing red blood cells. The lower right panel shows the magnified view of the boxed area in the lower left panel. Original magnification, x100 and x400 (lower right panel). (C) Upper: staining by HE and IHC for ALK. Note the strong ALK (5A4) immunoreactivity in tumor vasculature (indicated by boxes and magnified in the inset), as well as tumor cells around vascular components. Original magnification, x200 and x400 (inset). Middle and lower: staining by HE and ISH for ALK mRNA in GBMs. Note the positive ALK mRNA signals in tumor vasculature which are indicated by boxes in middle right panel and magnified in lower right panels (positive ALK mRNA signal in tumor vasculature are indicated by arrows), as well as tumor cells around vascular components. Original magnification, x200 and x400 (lower left panel).</p