Description: We present herein galaxy number counts of the nine bands in the 2–24 μm range on the basis of the AKARI North Ecliptic Pole (NEP) surveys. The number counts are derived from NEP-deep and NEP-wide surveys, which cover areas of 0.5 and 5.8 deg 2 , respectively. To produce reliable number counts, the sources were extracted from recently updated images. Completeness and difference between observed and intrinsic magnitudes were corrected by Monte Carlo simulation. Stellar counts were subtracted by using the stellar fraction estimated from optical data. The resultant source counts are given down to the 80 per cent completeness limit; 0.18, 0.16, 0.10, 0.05, 0.06, 0.10, 0.15, 0.16 and 0.44 mJy in the 2.4, 3.2, 4.1, 7, 9, 11, 15, 18 and 24 μm bands, respectively. On the bright side of all bands, the count distribution is flat, consistent with the Euclidean universe, while on the faint side, the counts deviate, suggesting that the galaxy population of the distant universe is evolving. These results are generally consistent with previous galaxy counts in similar wavebands. We also compare our counts with evolutionary models and find them in good agreement. By integrating the models down to the 80 per cent completeness limits, we calculate that the AKARI NEP survey revolves 20–50 per cent of the cosmic infrared background, depending on the wavebands.

Description: Most runoff analyses using a grid-based distributed model use one parameter group calibrated at the outlet of a watershed, instead of dividing the watershed into subwatersheds. Significant differences between the observed value and the simulation result of the subwatersheds can occur if just one parameter group is used in all subwatersheds that have different hydrological characteristics from each other. Therefore, to improve the simulation results of the subwatersheds within a watershed, a model calibrated at every subwatershed needs to be used to reflect the characteristics of each subwatershed. In this study, different parameter groups were set up for one or two sites using a distributed model, the GRM (Grid based Rainfall-runoff Model), and the evaluations were based on the results of rainfall-runoff analysis, which uses a multi-site calibration (MSC) technique to calibrate the model at the outlet of each site. The Hyangseok watershed in Naeseong River, which is a tributary of Nakdong River in Korea, was chosen as the study area. The watershed was divided into 5 subwatersheds each with a subwatershed outlet that was applied to the calibration sites. The MSC was applied for 5 cases. When a site was added for calibration in a watershed, the runoff simulation showed better results than the calibration of only one site at the most downstream area of the watershed. The MSC approach could improve the simulation results on the calibrated sites and even on the non-calibrated sites, and the effects of MSC improved when the calibrated site was closer to the runoff site. This article is protected by copyright. All rights reserved.

Description: The cellulosomes produced by Clostridium cellulovorans are organized by the specific interactions between the cohesins in the scaffolding proteins and the dockerins of the catalytic components. Using a cohesin biomarker, we identified a cellulosomal enzyme which belongs to the glycosyl hydrolase family 5 and has a domain of unknown function 291 (DUF291) with functions similar to those of the surface layer homology domain in C. cellulovorans . The purified endoglucanase G (EngG) had the highest synergistic degree with exoglucanase (ExgS) in the hydrolysis of crystalline cellulose (EngG/ExgS ratio = 3:1; 1.71-fold). To measure the binding affinity of the dockerins in EngG for the cohesins of the main scaffolding protein, a competitive enzyme-linked interaction assay was performed. Competitors, such as ExgS, reduced the percentage of EngG that were bound to the cohesins to less than 20%; the results demonstrated that the cohesins prefer to bind to the common cellulosomal enzymes rather than to EngG. Additionally, in surface plasmon resonance analysis, the dockerin in EngG had a relatively weak affinity (30- to 123-fold) for cohesins compared with the other cellulosomal enzymes. In the cell wall affinity assay, EngG anchored to the cell surfaces of C. cellulovorans using its DUF291 domain. Immunofluorescence microscopy confirmed the cell surface display of the EngG complex. These results indicated that in C. cellulovorans , EngG assemble into both the cellulolytic complex and the cell wall complex to aid in the hydrolysis of cellulose substrates.

Description: Purpose: To retrospectively evaluate whether dynamic contrast agent–enhanced (DCE) magnetic resonance (MR) imaging parameters assessed by a computer-aided evaluation program are associated with recurrence-free and overall survival in breast cancer patients who received neoadjuvant chemotherapy (NAC). Materials and Methods: This study was institutional review board approved and informed consent was waived. Between January 2007 and December 2009, 187 consecutive women (mean age, 46.6 years; range, 24–78 years) who had undergone NAC, DCE MR imaging before and after NAC, and surgery for invasive breast cancers (mean size, 5.0 cm; range, 2.0–14.8 cm on surgical histologic analysis) were identified. The tumor size, volume, and kinetic parameters (persistent, plateau, or washout components) were measured with a computer-aided evaluation program on DCE MR images before and after NAC, and their percentage changes were calculated. The Cox proportional hazards model was used to determine the association between DCE MR imaging parameters and recurrence-free survival and overall survival after controlling for clinical-pathologic variables. Results: There were 50 events, including 38 recurrences (29 distant, six local, and three both) and 12 deaths, at a mean follow-up of 47.4 months. At multivariate analysis, a smaller reduction in tumor volume (recurrence-free survival hazard ratio, 5.75; 95% confidence interval: 1.14, 8.64; and overall survival hazard ratio, 2.12; 95% confidence interval: 1.08, 5.69) and a smaller reduction in washout component (recurrence-free survival hazard ratio, 1.15; 95% CI: 1.06, 1.55; and overall survival hazard ratio, 1.26; 95% confidence interval: 1.03, 1.52) after NAC were independent significant variables for worse recurrence-free survival and overall survival. Conclusion: Smaller reduction in tumor volume and a smaller reduction in washout component on DCE MR images assessed with computer-aided evaluation after NAC were independent parameters of worse recurrence-free survival and overall survival in breast cancer patients who received NAC. © RSNA, 2013

Description: Purpose: Circulating endothelial cells (CEC) have been widely used as a prognostic biomarker and regarded as a promising strategy for monitoring the response to treatment in several cancers. However, the presence and biologic roles of CECs have remained controversial for decades because technical standards for the identification and quantification of CECs have not been established. Here, we hypothesized that CECs detected by flow cytometry might be monocytes rather than endothelial cells. Experimental Design: The frequency of representative CEC subsets (i.e., CD45 – /CD31 + , CD45 – /CD31 + /CD146 + , CD45 – /CD31 + /CD105 + ) was analyzed in the peripheral blood of patients with gynecologic cancer ( n = 56) and healthy volunteers ( n = 44). CD45 – /CD31 + cells, which are components of CECs, were isolated and the expression of various markers (CD146, CD105, vWF, and CD144 for endothelial cells; CD68 and CD14 for monocytes) was examined by immunocytochemistry. Results: CD45 – /CD31 + /CD105 + cells were significantly increased in the peripheral blood of patients with cancer, whereas evaluation of CD45 – /CD31 + /CD146 + cells was not possible both in patients with cancer and healthy controls due to the limited resolution of the flow cytometry. Immunocytochemistry analyses showed that these CD45 – /CD31 + /CD105 + cells did not express vWF and CD146 but rather CD144. Furthermore, CD45 – /CD31 + /CD105 + cells uniformly expressed the monocyte-specific markers CD14 and CD68. These results suggest that CD45 – /CD31 + /CD105 + cells carry the characteristics of monocytes rather than endothelial cells. Conclusions: Our data indicate that CD45 – /CD31 + /CD105 + circulating cells, which are significantly increased in the peripheral blood of patients with gynecologic cancer, are monocytes rather than endothelial cells. Further investigation is required to determine the biologic significance of their presence and function in relation with angiogenesis. Clin Cancer Res; 19(19); 5340–50. ©2013 AACR .

Description: Objective— Experimental evidence suggests that exenatide, a glucagon-like peptide 1 receptor analogue, has significant cardiovascular protective effects in various conditions. We examined whether routine use of exenatide at the time of primary percutaneous coronary intervention would reduce infarct size in patients with ST-segment–elevation myocardial infarction. Approach and Results— Fifty-eight patients with ST-segment–elevation myocardial infarction and thrombolysis in myocardial infarction flow 0 were enrolled in the study and randomly assigned to receive either exenatide or placebo (saline) subcutaneously. Infarct size was assessed by measuring the release of creatine kinase-MB and troponin I during 72 hours and by performing cardiac magnetic resonance imaging at 1 month after infarction. Routine and speckle tracking echocardiography was performed at initial presentation and at 3 days and 6 months after primary percutaneous coronary intervention. The exenatide and control groups had similar results with respect to ischemia time, demographic characteristics, and ejection fraction before primary percutaneous coronary intervention. The releases of creatine kinase-MB and troponin I were significantly reduced in the exenatide group. In 58 patients evaluated with cardiac magnetic resonance, the absolute mass of delayed hyperenhancement was significantly reduced in the exenatide group as compared with the control group (12.8±11.7 versus 26.4±11.6 g; P 〈0.01). At 6 months, the exenatide group showed a significantly lower value of E / E ' with improved strain parameters. No significant adverse effects of exenatide administration were detected. Conclusions— In patients with ST-segment–elevation myocardial infarction, adjunctive exenatide therapy with primary percutaneous coronary intervention was associated with reduction of infarct size and improvement of subclinical left ventricular function.

Description: Background— The pathophysiological basis for the association between metabolic syndrome (MetS) and coronary artery disease is not well understood. We sought to characterize coronary plaques in patients with MetS by using optical coherence tomography. Methods and Results— We identified 451 coronary plaques from 171 subjects who underwent optical coherence tomographic imaging in 3 coronary arteries. Subjects were divided into 3 groups: diabetes mellitus (DM, n=77), MetS (n=35), and a control group (C group, n=59) without DM or MetS. Optical coherence tomographic analysis included the presence of lipid-rich plaque, maximum lipid arc, lipid-core length, lipid index (LI), fibrous cap thickness, and thin-cap fibroatheroma. We defined LI as mean lipid arc multiplied by lipid-core length. Lipid-core length and LI were significantly greater in DM and MetS than in C group (lipid-core length: 7.7±4.0 and 7.0±3.8 versus 5.5±2.4 mm; P 〈0.001 and P =0.012, and LI: 1164±716 and 1086±693 versus 796±417 mm; P 〈0.001 and P =0.008). Maximum lipid arc was significantly greater in DM than in C group, whereas no significant difference was observed between MetS and C group (196±45°, 187±42° versus 176±52°; P =0.002 and P =0.182). Fibrous cap thickness and thin-cap fibroatheroma showed no significant difference among the 3 groups. In multivariate analysis, DM and MetS were independently associated with LI, whereas only acute coronary syndrome was the independent predictor for thin-cap fibroatheroma. Conclusions— Compared with control subjects, coronary plaques in MetS contain larger lipid. However, the MetS criteria used in this study could not distinguish the vulnerable features such as thin-cap fibroatheroma, suggesting the necessity of complementary information to identify patients at high risk for cardiovascular events.

Description: Purpose: To determine whether the ratio of the initial area under the time–signal intensity curve (AUC) (IAUC) to the final AUC—or AUCR—derived from dynamic contrast material–enhanced magnetic resonance (MR) imaging can be an imaging biomarker for distinguishing recurrent glioblastoma multiforme (GBM) from radiation necrosis and to compare the diagnostic accuracy of the AUCR with commonly used model-free dynamic contrast-enhanced MR imaging parameters. Materials and Methods: The institutional review board approved this retrospective study and waived the informed consent requirement. Fifty-seven consecutive patients with pathologically confirmed recurrent GBM ( n = 32) or radiation necrosis ( n = 25) underwent dynamic contrast-enhanced MR imaging. Histogram parameters of the IAUC at 30, 60, and 120 seconds and the AUCR, which included the mean value at the higher curve of the bimodal histogram (mAUCR H ), as well as 90th percentile cumulative histogram cutoffs, were calculated and were correlated with final pathologic findings. The best predictor for differentiating recurrent GBM from radiation necrosis was determined by means of receiver operating characteristic (ROC) curve analysis. Results: The demographic data were not significantly different between the two patient groups. There were statistically significant differences in all of the IAUC and AUCR parameters between the recurrent GBM and the radiation necrosis patient groups ( P 〈 .05 for each). ROC curve analyses showed mAUCR H to be the best single predictor of recurrent GBM (mAUCR H for recurrent GBM = 0.35 ± 0.11 [standard deviation], vs 0.19 ± 0.17 for radiation necrosis; P 〈 .0001; optimum cutoff, 0.23), with a sensitivity of 93.8% and a specificity of 88.0%. Conclusion: A bimodal histogram analysis of AUCR derived from dynamic contrast-enhanced MR imaging can be a potential noninvasive imaging biomarker for differentiating recurrent GBM from radiation necrosis. © RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130016/-/DC1

Description: Cystatin SN neutralizes the inhibitory effect of cystatin C on cathepsin B activity Cell Death and Disease 4, e974 (December 2013). doi:10.1038/cddis.2013.485 Authors: J-T Kim, S-J Lee, M A Kang, J E Park, B-Y Kim, D-Y Yoon, Y Yang, C-H Lee, Y I Yeom, Y-K Choe & H G Lee

Description: Objective— Allogeneic transplantation of human embryonic stem cell (hESC) derivatives has the potential to elicit the patient’s immune response and lead to graft rejection. Although hESCs and their derivatives have been shown to have advantageous immune properties in vitro, such observations could not be determined experimentally in vivo because of ethical and technical constraints. However, the generation of humanized mice (hu-mice) harboring a human immune system has provided a tool to perform in vivo immunologic studies of human cells and tissues. Using this model, we sought to examine the therapeutic potential of hESC-derived endothelial cells, human embryonic fibroblasts, and cord blood–derived endothelial progenitor cells in a human immune system environment. Approach and Results— All cell types transplanted in hu-mice showed significantly reduced cell survival during the first 14 days post-transplantation compared with that observed in immunodeficient mice. During this period, no observable therapeutic effects were detected in the hindlimb ischemic mouse models. After this point, the cells demonstrated improved survival and contributed to a long-term improvement in blood perfusion. All cell types showed reduced therapeutic efficacy in hu-mice compared with NOD scid IL2 receptor gamma chain knockout mice. Interestingly, the eventual improvement in blood flow caused by the hESC-derived endothelial cells in hu-mice was not much lower than that observed in NOD scid IL2 receptor gamma chain knockout mice. Conclusions— These findings suggest that hESC derivatives may be considered a good source for cell therapy and that hu-mice could be used as a preclinical in vivo animal model for the evaluation of therapeutic efficacy to predict the outcomes of human clinical trials.