Type 1 autoimmune pancreatitis

Before the concept of autoimmune pancreatitis (AIP) was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney) and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of regulatory T-cells are assumed to be involved in the underlying immune reaction. IgG4 antibodies have two unique biological functions, Fab-arm exchange and a rheumatoid factor-like activity, both of which may play immune-defensive roles. However, the exact role of IgG4 in this disease still remains to be clarified. It seems important to recognize this unique entity given that the disease is treatable with steroids

Fall vortex ozone as a predictor of springtime total ozone at high northern latitudes

Understanding the impact of atmospheric dynamical variability on observed changes in stratospheric O₃ is a key to understanding how O₃ will change with future climate dynamics and trace gas abundances. In this paper we examine the linkage between interannual variability in total column O₃ at northern high latitudes in March and lower-to-mid stratospheric vortex O₃ in the prior November. We find that these two quantities are significantly correlated in the years available from TOMS, SBUV, and POAM data (1978-2004). Additionally, we find that the increase in March O₃ variability from the 1980s to years post-1990 is also seen in the November vortex O₃, i.e., interannual variability in both quantities is much larger in the later years. The cause of this correlation is not clear, however. Interannual variations in March total O₃ are known to correspond closely with variations in winter stratospheric wave driving consistent with the effects of varying residual circulation, temperature, and chemical loss. Variation in November vortex O₃ may also depend on dynamical wave activity, but the dynamics in fall are less variable than in winter and spring. We do not find significant correlations of dynamic indicators for November such as temperature, heat flux, or polar average total O₃ with the November vortex O₃, nor with dynamical indicators later in winter and spring that might lead to a connection to March. We discuss several potential hypotheses for the observed correlation but do not find strong evidence for any considered mechanism. We present the observations as a phenomenon whose understanding may improve our ability to predict the dependence of O₃ on changing dynamics and chemistry

Safety and feasibility of Lin- cells administration to ALS patients : a novel view on humoral factors and miRNA profiles

Therapeutic options for amyotrophic lateral sclerosis (ALS) are still limited. Great hopes, however, are placed in growth factors that show neuroprotective abilities (e.g., nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF)) and in the immune modulating features, in particular, the anti-inflammatory effects. In our study we aimed to investigate whether a bone marrow-derived lineage-negative (Lin-) cells population, after autologous application into cerebrospinal fluid (CSF), is able to produce noticeable concentrations of trophic factors and inflammatory-related proteins and thus influence the clinical course of ALS. To our knowledge, the evaluation of Lin- cells transplantation for ALS treatment has not been previously reported. Early hematopoietic Lin- cells were isolated from twelve ALS patients’ bone marrow, and later, the suspension of cells was administered into the subarachnoid space by lumbar puncture. Concentrations of selected proteins in the CSF and plasma were quantified by multiplex fluorescent bead-based immunoassays at different timepoints post-transplantation. We also chose microRNAs (miRNAs) related to muscle biology (miRNA-1, miRNA-133a, and miRNA-206) and angiogenesis and inflammation (miRNA-155 and miRNA-378) and tested, for the first time, their expression profiles in the CSF and plasma of ALS patients after Lin- cells transplantation. The injection of bone marrow cells resulted in decreased concentration of selected inflammatory proteins (C3) after Lin- cells injection, particularly in patients who had a better clinical outcome. Moreover, several analyzed miRNAs have changed expression levels in the CSF and plasma of ALS patients subsequent to Lin- cells administration. Interestingly, the expression of miR-206 increased in ALS patients, while miR-378 decreased both in the CSF and plasma one month after the cells’ injection. We propose that autologous lineage-negative early hematopoietic cells injected intrathecally may be a safe and feasible source of material for transplantations to the central nervous system (CNS) environment aimed at anti-inflammatory support provision for ALS adjuvant treatment strategies. Further research is needed to evaluate whether the observed effects could significantly influence the ALS progression

Impact of doping and silicon substrate resistivity on the blistering of atomic-layer-deposited aluminium oxide

Aluminium oxide (Al2O3) thin films grown at low temperatures using atomic layer deposition (ALD) are known to often suffer from local delamination sites, referred to as "blisters", after post-deposition annealing during device processing. In this work, we report our observation that doping of the silicon substrate has an effect on blister formation. The introduction of a highly doped layer by diffusion or implantation is found to significantly reduce blistering, compared to the non-doped regions in the immediate vicinity. Similar behavior is observed for both phosphorus and boron doping. Further investigation of this phenomenon using substrates with different resistivities reveals that even when introduced already during silicon crystal growth, doping affects the blistering of aluminium oxide films. Changes in several properties of silicon affected by doping, most importantly surface terminating groups, native oxide growth, and passivation of defects with hydrogen, are discussed as potential reasons behind the observed effect on blistering.Peer reviewe

Comparing Global Atmospheric CO2 Flux and Transport Models with Remote Sensing (and Other) Observations

We report recent progress derived from comparison of global CO2 flux and transport models with new remote sensing and other sources of CO2 data including those from satellite. The overall objective of this activity is to improve the process models that represent our understanding of the workings of the atmospheric carbon cycle. Model estimates of CO2 surface flux and atmospheric transport processes are required for initial constraints on inverse analyses, to connect atmospheric observations to the location of surface sources and sinks, to provide the basic framework for carbon data assimilation, and ultimately for future projections of carbon-climate interactions. Models can also be used to test consistency within and between CO2 data sets under varying geophysical states. Here we focus on simulated CO2 fluxes from terrestrial vegetation and atmospheric transport mutually constrained by analyzed meteorological fields from the Goddard Modeling and Assimilation Office for the period 2000 through 2009. Use of assimilated meteorological data enables direct model comparison to observations across a wide range of scales of variability. The biospheric fluxes are produced by the CASA model at 1x1 degrees on a monthly mean basis, modulated hourly with analyzed temperature and sunlight. Both physiological and biomass burning fluxes are derived using satellite observations of vegetation, burned area (as in GFED-3), and analyzed meteorology. For the purposes of comparison to CO2 data, fossil fuel and ocean fluxes are also included in the transport simulations. In this presentation we evaluate the model's ability to simulate CO2 flux and mixing ratio variability in comparison to remote sensing observations from TCCON, GOSAT, and AIRS as well as relevant in situ observations. Examples of the influence of key process representations are shown from both forward and inverse model comparisons. We find that the model can resolve much of the synoptic, seasonal, and interannual variability in the observations, although reasons for persistent discrepancies in northern hemisphere vegetation uptake are examined. At this time, we do not find any serious shortcomings in the model transport representation, but this is still the subject of close scrutiny. In general, the fidelity of these simulations leads us to anticipate incorporation of real-time, highly resolved remote sensing and other observations into quantitative analyses that will reduce uncertainty in CO2 fluxes and revolutionize our understanding of the key processes controlling atmospheric CO2 and its evolution with time

Expression of selected angiogenesis-related small microRNAs in patients with abnormally increased secretion of glucocorticoids

Introduction: Higher cortisol levels are associated with cardiovascular morbidity and mortality in the elderly, partially resulting from biologic effects of glucocorticoids (GCs) on endothelial cells observed in an experimental setting. These features are replicated in patients with endogenous GC excess (Cushing’s syndrome) or with exogenous hypercortisolism due to excessive pharmacological application of GCs. Both groups present also an increased cardiovascular disease event rate. GCs may also adversely influence recovery after myocardial infarction. Recently it was proposed that microRNAs (miRNAs) — small noncoding RNAs functioning as antisense regulators of gene expression by targeting mRNA — may have a central role in regulating endothelial function through multiple mechanisms. Thus, the purpose of this study was to evaluate the effects of chronic GC excess on the expression of selected endothelium-controlling miRNAs expressed in nucleated cells circulating in peripheral blood (PBNCs) of patients with endogenous hypercortisolism either due to corticotrophin‐independent or corticotrophin‐dependent Cushing’s syndrome (CS). Material and methods: Peripheral blood nuclear cells were collected from 35 healthy subjects and 31 patients with endogenous hypercortisolism as a source of miRNAs. A self-validated individual quantitative RT-PCR study was then performed to evaluate the expression levels of selected miRNAs in PBNCs. Additionally, endothelin-1 (ET-1) expression in peripheral blood was assessed with respect to endothelial dysfunction using Western blotting. Results: The ET-1 expression levels in CS were higher than in controls, confirming endothelial dysfunction in the CS group. Furthermore, miRNA analysis revealed a significantly decreased intracellular expression of selected endothelium-related miRNAs in patients with endogenous hypercortisolism, including miRNA-17-5p, miRNA-126-3p, and miRNA-126-5p, compared to controls. In contrast, two other angiogenic miRNAs, miRNA-150-5p and miRNA-223-3p, were significantly upregulated compared to controls. Conclusions: Cardiovascular events related to hypercortisolism remain a challenging problem in medical practice. This study has demonstrated that the chronic excess of GCs in endogenous CS might induce significant dysregulation of selected miRNAs involved in the control of endothelium biology. However, the lack of knowledge about specific miRNA expression postpones the full understanding of the biological roles of such miRNAs in hypercortisolism. Moreover, dysregulated miRNAs seem to be promising targets for further research, especially to search for potential therapies for several GC-induced cardiovascular complications

Teleparallel Versions of Friedmann and Lewis-Papapetrou Spacetimes

This paper is devoted to investigate the teleparallel versions of the Friedmann models as well as the Lewis-Papapetrou solution. We obtain the tetrad and the torsion fields for both the spacetimes. It is shown that the axial-vector vanishes for the Friedmann models. We discuss the different possibilities of the axial-vector depending on the arbitrary functions $\omega$ and $\psi$ in the Lewis-Papapetrou metric. The vector related with spin has also been evaluated.Comment: 13 pages, accepted for publication in GR

Winter Bird Assemblages in Rural and Urban Environments: A National Survey

Urban development has a marked effect on the ecological and behavioural traits of many living organisms, including birds. In this paper, we analysed differences in the numbers of wintering birds between rural and urban areas in Poland. We also analysed species richness and abundance in relation to longitude, latitude, human population size, and landscape structure. All these parameters were analysed using modern statistical techniques incorporating species detectability. We counted birds in 156 squares (0.25 km2 each) in December 2012 and again in January 2013 in locations in and around 26 urban areas across Poland (in each urban area we surveyed 3 squares and 3 squares in nearby rural areas). The influence of twelve potential environmental variables on species abundance and richness was assessed with Generalized Linear Mixed Models, Principal Components and Detrended Correspondence Analyses. Totals of 72 bird species and 89,710 individual birds were recorded in this study. On average (±SE) 13.3 ± 0.3 species and 288 ± 14 individuals were recorded in each square in each survey. A formal comparison of rural and urban areas revealed that 27 species had a significant preference; 17 to rural areas and 10 to urban areas. Moreover, overall abundance in urban areas was more than double that of rural areas. There was almost a complete separation of rural and urban bird communities. Significantly more birds and more bird species were recorded in January compared to December. We conclude that differences between rural and urban areas in terms of winter conditions and the availability of resources are reflected in different bird communities in the two environments