Satellite Ocean Aerosol Retrieval (SOAR) algorithm extension to S-NPP VIIRS as part of the 'Deep Blue' aerosol project.

The Suomi National Polar-Orbiting Partnership (S-NPP) satellite, launched in late 2011, carries the Visible Infrared Imaging Radiometer Suite (VIIRS) and several other instruments. VIIRS has similar characteristics to prior satellite sensors used for aerosol optical depth (AOD) retrieval, allowing the continuation of space-based aerosol data records. The Deep Blue algorithm has previously been applied to retrieve AOD from Sea-viewing Wide Field-of-view Sensor (SeaWiFS) and Moderate Resolution Imaging Spectro-radiometer (MODIS) measurements over land. The SeaWiFS Deep Blue data set also included a SeaWiFS Ocean Aerosol Retrieval (SOAR) algorithm to cover water surfaces. As part of NASA's VIIRS data processing, Deep Blue is being applied to VIIRS data over land, and SOAR has been adapted from SeaWiFS to VIIRS for use over water surfaces. This study describes SOAR as applied in version 1 of NASA's S-NPP VIIRS Deep Blue data product suite. Several advances have been made since the SeaWiFS application, as well as changes to make use of the broader spectral range of VIIRS. A preliminary validation against Maritime Aerosol Network (MAN) measurements suggests a typical uncertainty on retrieved 550nm AOD of order ±(0.03+10%), comparable to existing SeaWiFS/MODIS aerosol data products. Retrieved Ångström exponent and fine mode AOD fraction are also well-correlated with MAN data, with small biases and uncertainty similar to or better than SeaWiFS/MODIS products.

Observations of the Interaction and Transport of Fine Mode Aerosols with Cloud and/or Fog in Northeast Asia from Aerosol Robotic Network (AERONET) and Satellite Remote Sensing.

Analysis of sun photometer measured and satellite retrieved aerosol optical depth (AOD) data has shown that major aerosol pollution events with very high fine mode AOD (>1.0 in mid-visible) in the China/Korea/Japan region are often observed to be associated with significant cloud cover. This makes remote sensing of these events difficult even for high temporal resolution sun photometer measurements. Possible physical mechanisms for these events that have high AOD include a combination of aerosol humidification, cloud processing, and meteorological co-variation with atmospheric stability and convergence. The new development of Aerosol Robotic network (AERONET) Version 3 Level 2 AOD with improved cloud screening algorithms now allow for unprecedented ability to monitor these extreme fine mode pollution events. Further, the Spectral Deconvolution Algorithm (SDA) applied to Level 1 data (L1; no cloud screening) provides an even more comprehensive assessment of fine mode AOD than L2 in current and previous data versions. Studying the 2012 winter-summer period, comparisons of AERONET L1 SDA daily average fine mode AOD data showed that Moderate Resolution Imaging Spectroradiometer (MODIS) satellite remote sensing of AOD often did not retrieve and/or identify some of the highest fine mode AOD events in this region. Also, compared to models that include data assimilation of satellite retrieved AOD, the L1 SDA fine mode AOD was significantly higher in magnitude, particularly for the highest AOD events that were often associated with significant cloudiness.

Cross-calibration of S-NPP VIIRS moderate resolution reflective solar bands against MODIS Aqua over dark water scenes.

The Visible Infrared Imaging Radiometer Suite (VIIRS) is being used to continue the record of Earth Science observations and data products produced routinely from National Aeronautics and Space Administration (NASA) Moderate Resolution Imaging Spectroradiometer (MODIS) measurements. However, the absolute calibration of VIIRS's reflected solar bands is thought to be biased, leading to offsets in derived data products such as aerosol optical depth (AOD) as compared to when similar algorithms are applied to different sensors. This study presents a cross-calibration of these VIIRS bands against MODIS Aqua over dark water scenes, finding corrections to the NASA VIIRS Level 1 (version 2) reflectances between approximately +1 % and -7 % (dependent on band) are needed to bring the two into alignment (after accounting for expected differences resulting from different band spectral response functions), and indications of relative trending of up to ^0.35 % per year in some bands. The derived calibration gain corrections are also applied to the VIIRS reflectance and then used in an AOD retrieval, and are shown to decrease the bias and total error in AOD across the midvisible spectral region compared to the standard VIIRS NASA reflectance calibration. The resulting AOD bias characteristics are similar to those of NASA MODIS AOD data products, which is encouraging in terms of multisensor data continuity.

Evaluation of NASA Deep Blue/SOAR aerosol retrieval algorithms applied to AVHRR measurements.

The Deep Blue (DB) and Satellite Ocean Aerosol Retrieval (SOAR) algorithms have previously been applied to observations from sen-sors like the Moderate Resolution Imaging Spectroradiometers (MODIS) and Sea-viewing Wide Field-of-view Sensor (SeaWiFS) to provide records of mid-visible aerosol optical depth (AOD) and related quantities over land and ocean surfaces respectively. Recently, DB and SOAR have also been applied to Ad-vanced Very High Resolution Radiometer (AVHRR) observations from several platforms (NOAA11, NOAA14, and NOAA18), to demonstrate the potential for extending the DB and SOAR AOD records. This study provides an evaluation of the initial version (V001) of the resulting AVHRR-based AOD data set, including validation against Aerosol Robotic Network (AERONET) and ship-borne observations, and comparison against both other AVHRR AOD Research (GESTAR), Universities Space Research Association. records and MODIS/SeaWiFS products at select long-term AERONET sites. Although it is difficult to distil error characteristics into a simple expression, the results suggest that one standard deviation confidence intervals on retrieved AOD of ±(0.03+15%) over water and ±(0.05+25%) over land represent the typical level of uncertainty, with a tendency towards negative biases in high-AOD conditions, caused by a combination of algorithmic assumptions and sensor calibration issues. Most of the available validation data are for NOAA18 AVHRR, although performance appears to be similar for the NOAA11 and NOAA14 sensors as well.

Fifteen-year global time series of satellite-derived fine particulate matter.

Ambient fine particulate matter (PM2.5) is a leading environmental risk factor for premature mortality. We use aerosol optical depth (AOD) retrieved from two satellite instruments, MISR and SeaWiFS, to produce a unified 15-year global time series (1998-2012) of ground-level PM2.5 concentration at a resolution of 1° x 1°. The GEOS-Chem chemical transport model (CTM) is used to relate each individual AOD retrieval to ground-level PM2.5. Four broad areas showing significant, spatially coherent, annual trends are examined in detail: the Eastern U.S. (-0.39 ± 0.10 µg m(-3) yr(-1)), the Arabian Peninsula (0.81 ± 0.21 µg m(-3) yr(-1)), South Asia (0.93 ± 0.22 µg m(-3) yr(-1)) and East Asia (0.79 ± 0.27 µg m(-3) yr(-1)). Over the period of dense in situ observation (1999-2012), the linear tendency for the Eastern U.S. (-0.37 ± 0.13 µg m(-3) yr(-1)) agrees well with that from in situ measurements (-0.38 ± 0.06 µg m(-3) yr(-1)). A GEOS-Chem simulation reveals that secondary inorganic aerosols largely explain the observed PM2.5 trend over the Eastern U.S., South Asia, and East Asia, while mineral dust largely explains the observed trend over the Arabian Peninsula.

Distant metastasis in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) relapses more frequently than hormone receptor-positive subtypes and is often associated with poor outcomes. This retrospective study reviewed the pattern of distant metastasis with regard to survival in patients with TNBC. A total of 205 TNBC patients were analyzed. TNBC patients with lung metastases had the longest median post-metastatic OS (with 95% confidence interval) of 16.6 (10.3-22.9) months, followed by the bone, 16.3 (11.7-20.8) months, the liver, 8.9 (3.5-14.4) months, the pleura, 7.5 (2.8-12.3) months, and the brain, 4.3 (0.6-8.0) months. Kaplan-Meier plots indicated that TNBC patients with metastatic spread to brain, liver, and pleural had poorer post-metastatic OS rate than patients with lung metastases (p = 0.001, 0.004, and 0.029, respectively). Moreover, brain and liver metastases correlated significantly with poorer post-metastatic OS as compared to bone metastasis (p = 0.004 and 0.011, respectively). Route of first metastasis correlated significantly with survival of TNBC patients with brain metastases being the poorest survival indicator, followed by metastases to liver, pleura, bone, and lung.

Risk factors for 30-day readmission in general medical patients admitted from the emergency department: a single centre study.

BACKGROUND: Overcrowding in emergency departments (ED) around the world is an increasingly serious problem with an adverse impact on both patient flow and patient outcomes. A significant contributing factor to ED overcrowding is possibly due to readmission. Risk factors for readmission in patients admitted from ED are rarely studied, particularly in Asian countries where the length of stay is reportedly longer. METHODS: A retrospective study of patients admitted to general medical wards from the ED of a referral centre in northern Taiwan from November 2009 to April 2010 was conducted. The primary outcome was 30-day hospital readmission and clinical characteristics were analysed for predictors of readmission. RESULTS: Of the recruited 2698 patients, 451 (16.7%) were readmitted within 30 days after discharge. Age, gender, marital status and the activities of daily living (Barthel's score) were not associated with 30-day readmission. Higher Charlson score ((score 2-4) hazard ratio (HR): 1.42, 95% confidence interval (CI): 1.07-1.89; (score >4) HR: 1.93, 95% CI: 1.37-2.73), longer hospital stay ((8-14 days) HR: 1.51, 95% CI: 1.17-1.95; (15-28 days) HR: 1.64, 95% CI: 1.22-2.19; (>28 days) HR: 1.97, 95% CI: 1.43-2.71), and presence of underlying active malignancy (HR: 1.66, 95% CI: 1.27-2.16) and anaemia (HR: 1.26, 95% CI: 1.02-1.55) were independently associated with readmission. CONCLUSION: Medical patients admitted from the ED of a referral centre have a 30-day readmission rate of 16.7%. Post-discharge care should focus on patients with higher Charlson score, longer hospitalisation, anaemia and underlying active malignancy, which are independent predictive factors for 30-day readmission.

Functions of the upstream and proximal steroidogenic factor 1 (SF-1)-binding sites in the CYP11A1 promoter in basal transcription and hormonal response.

The CYP11A1 gene encodes P450scc (cholesterol side-chain cleavage enzyme), which catalyzes the first step for the synthesis of steroids. Expression of CYP11A1 is controlled by transcription factor SF-1 (steroidogenic factor 1). Two functional SF-1-binding sites, P and U, located at -40 and -1,600 regions of the CYP11A1 gene, have been identified, but their exact functions with respect to basal activation vs. cAMP response have not been dissected. We have addressed this question by examining the ability of the mutated human CYP11A1 promoter to drive LacZ reporter gene expression in transgenic mouse lines. The activity of the mtP mutant promoter was greatly reduced, indicating the importance of the P site. Mutation of the upstream U site also resulted in reduced reporter gene expression, but some residual activity remained. This residual reporter gene activity was detected in the adrenal and gonad in a tissue-specific manner. ACTH and hCG can stimulate LacZ gene expression in the adrenals and testes of transgenic mice driven by the wild-type but not the mtU promoter. These results indicate that the upstream SF-1-binding site is required for hormonal stimulation. Our experiments demonstrate the participation of both the proximal and the upstream SF-1-binding sites in hormone-responsive transcription.

Regulation of steroidogenesis in transgenic mice and zebrafish.

Steroid hormones are important physiological regulators in the body. Steroid hormones are mainly synthesized in the adrenal and gonads. Their synthesis is stimulated by pituitary hormones through cAMP as an intracellular mediator. The first and rate-limiting step for steroid biosynthesis is catalyzed by CYP11A1. Important regulatory elements for the control of the CYP11A1 gene expression have been characterized both in vitro and in vivo. The SF-1-binding sites are cis-acting elements controlling the basal and cAMP-stimulated gene expression. Our transgenic mouse studies showed that the 2.3kb promoter contains information controlling developmentally regulated gene expression. Finally, we present our results on the cloning of steroidogenic genes in zebrafish, a new model organism for genetic studies.

Tissue-specific, hormonal, and developmental regulation of SCC-LacZ expression in transgenic mice leads to adrenocortical zone characterization.

We report here the study of the human CYP11A1 promoter in driving tissue-specific, developmentally and hormonally regulated reporter gene expression. A 4.4-kb fragment containing all known regulatory elements is more efficient than a short basal promoter fused to an upstream adrenal enhancer in driving reporter LacZ gene expression both in cell culture and in transgenic mice. The LacZ gene controlled by the 4.4- and 2.3-kb promoters was expressed in the adrenal cortex, testicular Leydig cells, ovarian corpora lutea, and granulosa cells. Transgene expression in the adrenals was stimulated by ACTH, indicating the presence of ACTH-responsive sequence. Beta-galactosidase activity was first detected in the adrenal primordia at 11.5 days postcoitum. Its expression continued throughout all stages of adrenal development in a pattern similar to that of the endogenous CYP11A1, which was expressed in all zones of the adrenal cortex, but was strongest in the X zone. The X zone grew before puberty but regressed afterward, as did the levels of CYP11A1 and LacZ gene expression in the X zone. Our study of the CYP11A1 promoter in transgenic mice led to characterization of the adrenocortical zones.

Function of steroidogenic factor 1 domains in nuclear localization, transactivation, and interaction with transcription factor TFIIB and c-Jun.

Normal endocrine development and function require nuclear hormone receptor SF-1 (steroidogenic factor 1). To understand the molecular mechanism of SF-1 action, we have investigated its domain function by mutagenesis and functional analyses. Our mutant studies show that the putative AF2 (activation function 2) helix located at the C-terminal end is indispensable for gene activation. SF-1 does not have an N-terminal AF1 domain. Instead, it contains a unique FP region, composed of the Ftz-F1 box and the proline cluster, after the zinc finger motif. The FP region interacts with transcription factor IIB (TFIIB) in vitro. This interaction requires residues 178-201 of TFIIB, a domain capable of binding several transcription factors. The FP region also mediates physical interaction with c-Jun, and this interaction greatly enhances SF-1 activity. The putative SF-1 ligand, 25-hydroxycholesterol, has no effects on these bindings. In addition, the Ftz-F1 box contains a bipartite nuclear localization signal (NLS). Removing the basic residues at either end of the key nuclear localization sequence NLS2.2 abolishes the nuclear transport. Expression of mutants containing only the FP region or lacking the AF2 domain blocks wild-type SF-1 activity in cells. By contrast, the mutant having a truncated nuclear localization signal lacks this dominant negative effect. These results delineate the importance of the FP and AF2 regions in nuclear localization, protein-protein interaction, and transcriptional activation.

Characterization of the consequence of a novel Glu-380 to Asp mutation by expression of functional P450c21 in Escherichia coli.

P450c21 catalyzes an important step in steroid synthesis. Its deficiency leads to symptoms of steroid imbalance. To obtain enough P450c21 for structure and function studies, we developed a method to express P450c21 in Escherichia coli. The 5'-region of the human P450c21 cDNA was modified to ensure efficient translation and the C terminus of the protein was extended with four His residues for easy purification. Mutant proteins with substitutions at residues 172 and 281 exhibited decreased enzymatic activities similar to those found in mammalian cells. One new mutation changing Glu-380 to Asp (D380) caused 3-fold reduction in enzymatic activity. The amount of apoprotein production detected by immunoblotting and the affinity of the mutant protein towards substrate as measured by Km were normal. The defect lies in the decreased ability of the apoprotein to bind heme, which was measured by CO difference and substrate-binding spectra. The D380 mutant protein had 3-fold reduction in peak heights in both spectra. This reduced heme binding resulted in 3-fold lower enzymatic activity.

Interferon-alpha and granulocyte-macrophage colony-stimulating factor differentiate peripheral blood monocytes into potent antigen-presenting cells.

The diverse roles of interferon-alpha (IFN-alpha) in regulating the immune response to infectious agents suggested that it might affect dendritic cell (DC) development. Peripheral blood mononuclear cells cultured with IFN-alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) developed a dendritic morphology and expressed high levels of the class I and II human leukocyte antigens (HLA), B7 co-stimulatory molecules, adhesion proteins, and CD40. Elevated DC expression of B7-2 and HLA-DR was observed with increasing IFN-alpha concentrations up to 5000 U/mL. The effects of IFN-alpha on DC immunophenotype were not reversed by adding neutralizing antibodies against interleukin-4 (IL-4) or tumor necrosis factor alpha to the cell cultures or by eliminating lymphocytes from the cultures. The addition of IFN-alpha to cultures containing optimal concentrations of IL-4 and GM-CSF significantly increased the B7-2 and HLA-DR levels above those present on DCs grown in two cytokines. The DCs generated with IFN-alpha and GM-CSF were potent antigen-presenting cells in allogeneic mixed leukocyte reactions. They also were capable of taking up, processing, and presenting tetanus toxin to autologous T lymphocytes. These results demonstrate an important role for IFN-alpha in the generation of DCs with potent antigen-presenting capabilities from peripheral blood monocytes.

Local synthesis of C3 within the splenic lymphoid compartment can reconstitute the impaired immune response in C3-deficient mice.

Mice bearing a disrupted C3 locus (C3-/-) have an impaired Ab response to T-dependent Ags (bacteriophage phiX 174 and nuclear protein-keyhole limpet hemocyanin) characterized by a reduction in number and size of germinal centers and impaired retention of Ag by follicular dendritic cells. To test the importance of C3 synthesized locally within the lymphoid compartment during an immune response to T-dependent Ag, we reconstituted C3-/- mice with wild-type bone marrow of MHC-identical littermates. Engraftment not only restored local C3 synthesis in the spleen, but also rescued the impaired humoral response. The major source of C3 mRNA was MOMA-2+ macrophages localized within the white pulp areas of the spleen. Interestingly, C3 expression is apparently regulated as C3 mRNA was not detected in splenic sections of nonimmune mice. Furthermore, local C3 synthesis by donor macrophages reversed the impaired Ag trapping by splenic follicular dendritic cells in C3-deficient mice.

Function and membrane topology of wild-type and mutated cytochrome P-450c21.

We have studied membrane topology of cytochrome P-450c21 (P450c21) using the approaches of mutagenesis and protease digestion. P450c21 is located at the cytoplasm with an N-terminal hydrophobic domain integrated into microsomal membranes. When this hydrophobic domain was replaced by a secretory signal peptide, P450c21 was translocated into the lumen and lost enzymic activity. No other topogenic sequence was detected in the bulk of the P450c21 peptide. A mutant protein with Pro-30 replaced by Leu (L30) corresponding to the mutation found in the diseased state was created. L30 protein lost 90% of enzymic activity, while a double mutant (L30R32) with an additional Leu-32 to Arg mutation had slightly higher residual enzymic activity. Apart from lower activity, L30 was also present in the cell at a lower level than wild-type P450c21. This lower level is probably due to increased degradation, as L30 is synthesized at a normal rate. Both L30 and L30R32 proteins, however, were integrated into membranes normally. Therefore the Pro-30 --> Leu mutation did not affect membrane integration, but affected the abundance and enzymic activity of P450c21.

The common I172N mutation causes conformational change of cytochrome P450c21 revealed by systematic mutation, kinetic, and structural studies.

We have investigated the structure and function of P450c21 with regard to a conserved site around Ile-172 by site-directed mutagenesis making single amino acid substitutions of residues 169 173. Substitutions of Ile-171 and -172 resulted in production of mutant proteins with dramatic reductions in enzymatic activities, indicating the importance of these two residues in maintaining the structure and function of P450c21. The I171N protein was present at a slightly lower level, due to a decreased rate of protein synthesis. The I172N apoprotein was synthesized at the normal rate, but its heme-bound P450 form was present at a much lower level. This I172N protein was tightly integrated into the membrane of endoplasmic reticulum, similar to the wild type P450c21, as shown by immunofluorescence detection, alkaline extraction, and cellular fractionation. Kinetic studies indicated that I172N had a lower Vmax value. In addition, the I172N protein was more sensitive to proteinase K digestion, indicating a possible alteration of conformation. This conformational change may result in the lower yield of the I172N hemoprotein and the reduced catalytic activity.

Analysis of c-kit gene integrity in aplastic anemia.

Mice harboring the "white spotting" (W) locus have abnormalities in hematopoiesis due to one of various mutations of the c-kit proto-oncogene, which encodes the stem cell factor (SCF) receptor. The c-kit mutations identified in W mice cause diminished, absent or dominant negative receptor function. This study explores the hypothesis that acquired mutations of c-kit in the hematopoietic stem cell participate in the pathogenesis of aplastic anemia (AA). Genomic DNA was prepared from granulocytes and monocytes of 11 patients with acquired AA and one patient with a non-Fanconi's form of inherited AA. DNA was subjected to polymerase chain reaction (PCR) amplification and single-stranded conformation polymorphism (SSCP) analysis for all 21 exons of the c-kit gene. Two patients were heterozygous for a previously described polymorphism involving exon 17. Two other patient samples had an extra band on SSCP analysis of exon 10. DNA extracted from epithelial cells of one patient revealed the same SSCP pattern as that from the blood cells, suggesting that the alteration was in the germ-line. PCR-SSCP analysis of leukocyte DNA from 12 normal individuals revealed that 2 samples also had an extra band in exon 10. DNA sequencing of PCR-amplified and cloned DNA from the patients and the normal individuals with the aberrant SSCP results showed them all to be heterozygous for an ATG to CTG transition in codon 541, resulting in substitution of methionine by leucine in the transmembrane region of the protein. The same two patients and two controls were heterozygous for a silent change in codon 862 (exon 18). Matching serum samples from 4 of 6 AA patients tested had SCF levels more than two standard deviations above the normal mean value. These results suggest that neither c-kit mutations nor decreased soluble SCF levels are commonly involved in the pathogenesis of acquired AA.

Identification of an internal promoter of the latent membrane protein 1 gene of Epstein-Barr virus.

The latent membrane protein 1 (LMP 1) gene of an Epstein-Barr virus (EBV) variant derived from an nasopharyngeal carcinoma (NPC) biopsy in Taiwan was isolated and characterized (Chen et al., 1992). Transient expression of the genomic sequence containing this gene showed two proteins with molecular masses of 62 kD and 50 kD, respectively, recognized by LMP-specific antibody S12. To determine if these two proteins were derived from independent promoters, we generated a series of mutant plasmids from plasmid pT7(E) that contained the upstream and the coding regions of the LMP 1 gene. These mutants were introduced into a human epithelial cell line, C33A, and LMP 1 proteins were examined by Western blotting analysis with the S12 antibody. Data showed that plasmid with a fragment containing approximately 3 kb of upstream sequence of LMP 1 gene produced the 62-kD protein. Removal of 2.7 kb of the upstream sequence (plasmid delta 2710, deleted to nucleotide 169,571) resulted in the production of both 62-kD and 50-kD proteins. This suggested that the upstream sequence interfered with the production of the 50-kD protein. Plasmid DNA deleted to Acc I site (nucleotide 169,223) generated only the 50-kD protein, designated as tr-LMP. Further deletion to nucleotide 169,038 resulted in the expression of another smaller LMP1 (49 kD, named as str-LMP1). The region between nucleotides 168,789 and 169,038 was tested to see if it possessed a promoter activity by using the luciferase gene as a reporter. Data showed that this region contained promoter activity with a level compatible to the previously reported ED-L1A promoter.(ABSTRACT TRUNCATED AT 250 WORDS)