Analysis of GPS radio occultation data from the FORMOSAT-3/COSMIC and Metop/GRAS missions at CDAAC

This study investigates the noise level and mission-to-mission stability of Global Positioning System (GPS) radio occultation (RO) neutral atmospheric bending angle data at the UCAR COSMIC Data Analysis and Archive Center (CDAAC). Data are used from two independently developed RO instruments currently flying in orbit on the FORMOSAT-3/COSMIC (F3C) and Metop/GRAS (GNSS Receiver for Atmospheric Sounding) missions. The F3C 50 Hz RO data are post-processed with a single-difference excess atmospheric phase algorithm, and the Metop/GRAS 50 Hz closed loop and raw sampling (down-sampled from 1000 Hz to 50 Hz) data are processed with a zero-difference algorithm. The standard deviations of the F3C and Metop/GRAS bending angles from climatology between 60 and 80 km altitude from June–December 2009 are approximately 1.78 and 1.13 μrad, respectively. The F3C standard deviation reduces significantly to 1.44 μrad when single-difference processing uses GPS satellites on the same side of the spacecraft. The higher noise level for F3C bending angles can be explained by additional noise from the reference link phase data that are required with single-difference processing. The F3C and Metop/GRAS mean bending angles differences relative to climatology during the same six month period are statistically significant and have values of −0.05 and −0.02 μrad, respectively. A comparison of ~13 500 collocated F3C and Metop/GRAS bending angle profiles over this six month period shows a similar mean difference of ~0.02 ± 0.02 μrad between 30 and 60 km impact heights that is marginally significant. The observed mean difference between the F3C and Metop/GRAS bending angles of ~0.02–0.03 μrad is quite small and illustrates the high degree of re-produceability and mission independence of the GPS RO data at high altitudes. Collocated bending angles between two F3C satellites from early in the mission differ on average by up to 0.5% near the surface due to systematically lower signal-to-noise ratio for one of the satellites. Results from F3C and Metop/GRAS differences in the lower troposphere suggest the Metop/GRAS bending angles are negatively biased compared to F3C with a maximum of several percents near the surface in tropical regions. This bias is related to different tracking depths (deeper in F3C) and data gaps in Metop/GRAS which make it impossible to process the data from both missions in exactly the same way

Pitfalls in the characterization of circulating and tissue-resident human γδ T cells

Dissection of the role and function of human γδ T cells and their heterogeneous subsets in cancer, inflammation, and auto-immune diseases is a growing and dynamic research field of increasing interest to the scientific community. Therefore, harmonization and standardization of techniques for the characterization of peripheral and tissue-resident γδ T cells is crucial to facilitate comparability between published and emerging research. The application of commercially available reagents to classify γδ T cells, in particular the combination of multiple Abs, is not always trouble-free, posing major demands on researchers entering this field. Occasionally, even entire γδ T cell subsets may remain undetected when certain Abs are combined in flow cytometric analysis with multicolor Ab panels, or might be lost during cell isolation procedures. Here, based on the recent literature and our own experience, we provide an overview of methods commonly employed for the phenotypic and functional characterization of human γδ T cells including advanced polychromatic flow cytometry, mass cytometry, immunohistochemistry, and magnetic cell isolation. We highlight potential pitfalls and discuss how to circumvent these obstacles

The insertion/deletion (I/D) polymorphism in the Angiotensin-converting enzyme gene and cancer risk: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>The insertion/deletion (I/D) polymorphism in the <it>Angiotensin-converting enzyme </it>(<it>ACE</it>) gene has been implicated in susceptibility to cancer, but a large number of studies have reported inconclusive results. The aim of this study is to assess the association between the I/D polymorphism in the <it>ACE </it>gene and cancer risk by meta-analysis.</p> <p>Methods</p> <p>A search was performed in Pubmed database, Embase database, Chinese Biomedical (CBM) database, China National Knowledge Infrastructure (CNKI) database and Weipu database, covering all studies until August 31, 2010. Statistical analysis was performed by using Revman4.2 and STATA 10.0.</p> <p>Results</p> <p>A total of 25 case-control studies comprising 3914 cancer patients and 11391 controls were identified. No significant association was found between the I/D polymorphism and over all cancer risks (OR = 0.88, 95%CI = 0.73-1.06, P = 0.17 for DD+DI vs. II). In the subgroup analysis by ethnicity, no significant association was found among Asians and Europeans for the comparison of DD+DI vs. II. In the subgroup analysis by cancer types, no significant associations were found among lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer for the comparison of DD+DI vs. II. Results from other comparative genetic models also indicated the lack of associations between this polymorphism and cancer risks.</p> <p>Conclusions</p> <p>This meta-analysis suggested that the <it>ACE </it>D/I polymorphism might not contribute to the risk of cancer.</p

European consensus statement on phenotypes of pustular psoriasis

Pustularpsoriasis (PP) isagroupof inflammatoryskinconditionscharacterizedby infiltrationofneutrophil granulocytes in theepidermis tosuchanextent that clinicallyvisiblesterilepustulesdevelop.Becauseof clinical co-incidence, PP is currently groupedwith psoriasis vulgaris (PV). However, PP andPV are phenotypically different, responddifferently totreatmentsandseemtobedistinctonthegenetic level. Incontrast toPV, thephenotypesof PParenotwell defined.Descriptionsof each formof PParediscordant amongstandarddermatology textbooks [SauratDermatologie2016, Rook’sDermatology2016, Fitzpatrick’s2012andBraun-Falco2012], encumbering the collectionofphenotypicallywell-matchedgroupsofpatientsaswellasclinical trials.TheEuropeanRareandSevere PsoriasisExpertNetwork(ERASPEN)wasfoundedtodefineconsensuscriteriafordiagnosis,deeplyphenotypelarge groupsofPPpatients,analysethegeneticsandpathophysiologyandprepareforprospectiveclinical trials.Thiswork reviewshistorical aspectsof theseconditions, newgeneticfindingsandpresentsour initial considerationson the phenotypesofPPandaconsensusclassificationof clinical phenotypes thatwill beusedasabaseline for further, prospectivestudiesofPP.Generalizedpustularpsoriasis(GPP) isdefinedasprimary,sterile,macroscopicallyvisible pustulesonnon-acralskin(excludingcaseswherepustulationisrestrictedtopsoriaticplaques).GPPcanoccurwith or without systemic inflammation, with or without PV and can either be a relapsing (&gt;1 episode) or persistent (&gt;3months) condition. Acrodermatitis continua of Hallopeau (ACH) is characterized by primary, persistent (&gt;3months), sterile,macroscopicallyvisiblepustulesaffectingthenail apparatus.Palmoplantarpustulosis (PPP) has primary, persistent (&gt;3months), sterile,macroscopicallyvisiblepustulesonpalmsand/or solesandcanoccurwith orwithoutPV

AA-Amyloidosis Can Be Transferred by Peripheral Blood Monocytes

Spongiform encephalopathies have been reported to be transmitted by blood transfusion even prior to the clinical onset. Experimental AA-amyloidosis shows similarities with prion disease and amyloid-containing organ-extracts can prime a recipient for the disease. In this systemic form of amyloidosis N-terminal fragments of the acute-phase reactant apolipoprotein serum amyloid A are the main amyloid protein. Initial amyloid deposits appear in the perifollicular region of the spleen, followed by deposits in the liver. We used the established murine model and induced AA-amyloidosis in NMRI mice by intravenous injections of purified amyloid fibrils (‘amyloid enhancing factor’) combined with inflammatory challenge (silver nitrate subcutaneously). Blood plasma and peripheral blood monocytes were isolated, sonicated and re-injected into new recipients followed by an inflammatory challenge during a three week period. When the animals were sacrificed presence of amyloid was analyzed in spleen sections after Congo red staining. Our result shows that some of the peripheral blood monocytes, isolated from animals with detectable amyloid, contained amyloid-seed that primed for AA-amyloid. The seeding material seems to have been phagocytosed by the cells since the AA-precursor (SAA1) was found not be expressed by the monocytes. Plasma recovered from mice with AA amyloidosis lacked seeding capacity. Amyloid enhancing activity can reside in monocytes recovered from mice with AA-amyloidosis and in a prion-like way trigger amyloid formation in conjunction with an inflammatory disorder. Human AA-amyloidosis resembles the murine form and every individual is expected to be exposed to conditions that initiate production of the acute-phase reactant. The monocyte-transfer mechanism should be eligible for the human disease and we point out blood transfusion as a putative route for transfer of amyloidosis

Angiotensin-2 receptors (AT1-R and AT2-R), new prognostic factors for renal clear-cell carcinoma?

International audienceBackground: The growth factor Angiotensin-2 signals through Angiotensin receptor type 1 (AT1-R) in a broad range of cell types and tumours and through the type-2 receptor (AT2-R) in a more restricted group of cell types. Although numerous forms of cancer have been shown to overexpress AT1-R, expression of AT1-R and AT2-R by human renal clear-cell carcinoma (RCCC) is not well understood. In this study, the expression of both angiotensin receptors was quantified in a retrospective series of RCCC and correlated with prognostic factors.Methods: Angiotensin receptor type 1 and AT2-R expressions were quantified on tumour tissues by immunohistochemistry (IHC), western blot and quantitative reverse transcriptase PCR (qRT–PCR). IHC results were correlated to Fuhrman's grade and patient progression-free survival (PFS).Results: A total of 84 RCCC were analysed. By IHC, AT1-R and AT2-R were expressed to a greater level in high-grade tumours (AT1-R: P<0.001, AT2-R: P<0.001). Univariate analysis showed a correlation between PFS and AT1-R or AT2-R expression (P=0.001). By multivariate analysis, only AT2-R expression correlated with PFS (HR 1.021, P=0.006) and cancer stage (P<0.001). By western blot, AT1-R and AT1-R were also found to be overexpressed in higher Fuhrman's grade (P<0.01 and P=0.001 respectively). By qRT–PCR, AT1-R but not AT2-R mRNA were downregulated (P=0.001 and P=0.118, respectively).Conclusion: Our results show that AT1-R and AT2-R proteins are overexpressed in the most aggressive forms of RCCC and that AT2-R expression correlates with PFS. AT1-R or AT2-R blockage could, therefore, offer novel directions for anti-RCCC therapy

249 TP53 mutation has high prevalence and is correlated with larger and poorly differentiated HCC in Brazilian patients

<p>Abstract</p> <p>Background</p> <p>Ser-249 TP53 mutation (249^Ser) is a molecular evidence for aflatoxin-related carcinogenesis in Hepatocellular Carcinoma (HCC) and it is frequent in some African and Asian regions, but it is unusual in Western countries. HBV has been claimed to add a synergic effect on genesis of this particular mutation with aflatoxin. The aim of this study was to investigate the frequency of 249^Sermutation in HCC from patients in Brazil.</p> <p>Methods</p> <p>We studied 74 HCC formalin fixed paraffin blocks samples of patients whom underwent surgical resection in Brazil. 249^Sermutation was analyzed by RFLP and DNA sequencing. HBV DNA presence was determined by Real-Time PCR.</p> <p>Results</p> <p>249^Sermutation was found in 21/74 (28%) samples while HBV DNA was detected in 13/74 (16%). 249^Sermutation was detected in 21/74 samples by RFLP assay, of which 14 were confirmed by 249^Sermutant-specific PCR, and 12 by nucleic acid sequencing. All HCC cases with p53-249ser mutation displayed also wild-type p53 sequences. Poorly differentiated HCC was more likely to have 249^Sermutation (OR = 2.415, 95% CI = 1.001 – 5.824, p = 0.05). The mean size of 249^SerHCC tumor was 9.4 cm versus 5.5 cm on wild type HCC (p = 0.012). HBV DNA detection was not related to 249^Sermutation.</p> <p>Conclusion</p> <p>Our results indicate that 249^Sermutation is a HCC important factor of carcinogenesis in Brazil and it is associated to large and poorly differentiated tumors.</p