Impact of IL8 and IL8-Receptor alpha polymorphisms on the genetics of bronchial asthma and severe RSV infections

BACKGROUND: Interleukin 8 (IL8) belongs to the family of chemokines. It mediates the activation and migration of neutrophils from peripheral blood into tissue and hereby plays a pivotal role in the initiation of inflammation. Thus it is important in inflammatory lung diseases like bronchial asthma or severe infections by Respiratory Syncytial Virus (RSV). IL8 acts through binding to the IL8-Receptor alpha (IL8RA). For both genes association with asthma has been described. In addition, IL8 has been found in association with RSV bronchiolitis. The aim of our study was to test both genes for association with asthma and severe RSV infections. In addition we were interested in whether a common genetic background of both diseases exists in regards to these genes. METHODS: We genotyped the two IL8 promotor polymorphisms -251A/T and -781C/T and the three amino acid variants M31R, S276T and R335C in IL8RA on 322 children with asthma, 131 infants with severe RSV associated diseases and 270 controls. Statistical analyses made use of the Armitage's trend test for single polymorphisms and FAMHAP for calculations of haplotypes. RESULTS: We found association of the IL8 polymorphism -781C/T as well as IL8 haplotypes with asthma (p = 0.011 and p = 0.036, respectively). In addition, direct comparison of the asthmatic population with the RSV population revealed significant differences, both for -781C/T alone (p = 0.034) and IL8 haplotypes (p = 0.005). The amino acid variants in IL8RA were evenly distributed in between all three populations. CONCLUSION: We conclude from our data that IL8 might play a role in the genetic predisposition to asthma and that these effects are different or even opposite to the effects on severe RSV diseases. Furthermore, IL8RA is unlikely to play a major role in the genetics of either disease

How to Juggle Columns: An Entropy-Based Approach for Table Compression

Many relational databases exhibit complex dependencies between data attributes, caused either by the nature of the underlying data or by explicitly denormalized schemas. In data warehouse scenarios, calculated key figures may be materialized or hierarchy levels may be held within a single dimension table. Such column correlations and the resulting data redundancy may result in additional storage requirements. They may also result in bad query performance if inappropriate independence assumptions are made during query compilation. In this paper, we tackle the specific problem of detecting functional dependencies between columns to improve the compression rate for column-based database systems, which both reduces main memory consumption and improves query performance. Although a huge variety of algorithms have been proposed for detecting column dependencies in databases, we maintain that increased data volumes and recent developments in hardware architectures demand novel algorithms with much lower runtime overhead and smaller memory footprint. Our novel approach is based on entropy estimations and exploits a combination of sampling and multiple heuristics to render it applicable for a wide range of use cases. We demonstrate the quality of our approach by means of an implementation within the SAP NetWeaver Business Warehouse Accelerator. Our experiments indicate that our approach scales well with the number of columns and produces reliable dependence structure information. This both reduces memory consumption and improves performance for nontrivial queries

Cyanobacteria net community production in the Baltic Sea as inferred from profiling pCO(2) measurements

Organic matter production by cyanobacteria blooms is a major environmental concern for the Baltic Sea, as it promotes the spread of anoxic zones. Partial pressure of carbon dioxide (pCO(2)) measurements carried out on Ships of Opportunity (SOOP) since 2003 have proven to be a powerful tool to resolve the carbon dynamics of the blooms in space and time. However, SOOP measurements lack the possibility to directly constrain depth-integrated net community production (NCP) in moles of carbon per surface area due to their restriction to the sea surface. This study tackles the knowledge gap through (1) providing an NCP best guess for an individual cyanobacteria bloom based on repeated profiling measurements of pCO(2) and (2) establishing an algorithm to accurately reconstruct depth-integrated NCP from surface pCO(2) observations in combination with modelled temperature profiles.Goal (1) was achieved by deploying state-of-the-art sensor technology from a small-scale sailing vessel. The low-cost and flexible platform enabled observations covering an entire bloom event that occurred in July-August 2018 in the Eastern Gotland Sea. For the biogeochemical interpretation, recorded pCO(2) profiles were converted to C-T*, which is the dissolved inorganic carbon concentration normalised to alkalinity. We found that the investigated bloom event was dominated by Nodularia and had many biogeochemical characteristics in common with blooms in previous years. In particular, it lasted for about 3 weeks, caused a C-T* drawdown of 90 mu mol kg(-1), and was accompanied by a sea surface temperature increase of 10 degrees C. The novel finding of this study is the vertical extension of the C-T* drawdown up to the compensation depth located at around 12 m. Integration of the C-T* drawdown across this depth and correction for vertical fluxes leads to an NCP best guess of similar to 1:2 mol m(-2) over the productive period.Addressing goal (2), we combined modelled hydrographical profiles with surface pCO(2) observations recorded by SOOP Finnmaid within the study area. Introducing the temperature penetration depth (TPD) as a new parameter to integrate SOOP observations across depth, we achieve an NCP reconstruction that agrees to the best guess within 10 %, which is considerably better than the reconstruction based on a classical mixed-layer depth constraint.Applying the TPD approach to almost 2 decades of surface pCO(2) observations available for the Baltic Sea bears the potential to provide new insights into the control and long-term trends of cyanobacteria NCP. This understanding is key for an effective design and monitoring of conservation measures aiming at a Good Environmental Status of the Baltic Sea

Study of drag and orientation of regular particles using stereo vision, Schlieren photography and digital image processing

© 2017 Elsevier B.V.A new experimental, image-based methodology suitable to track the changes in orientation of non-spherical particles and their influence on the drag coefficient as they settle in fluids is presented. Given the fact that non-spherical solids naturally develop variations in their angular orientation during the fall, none-intrusiveness of the technique of analysis is of paramount importance in order to preserve the particle/fluid interaction undisturbed. Three-dimensional quantitative data about the motion parameters is obtained through single-camera stereo vision whilst qualitative visualizations of the adjacent fluid patterns are achieved with Schlieren photography. The methodology was validated by comparing the magnitudes of the drag coefficient of a set of spherical particles at terminal velocity conditions against those estimated from drag correlations published in the literature. A noteworthy similarity was attained. During the fall of non-spherical solids, once the particle Reynolds number approximated 163 for disks, and 240 for cylinders, or exceeded those values, secondary motions composed by regular oscillations and tumbling were present. They altered the angular orientation of the particles with respect to the main motion direction and caused complete turbulent patterns in the surrounding flow, therefore affecting the instantaneous projected area, drag force, and coefficient of resistance. The impact of the changes in angular orientation onto the drag coefficient was shown graphically as a means for reinforcing existing numerical approaches, however, an explicit relation between both variables could not be observed

On an Analytical Model for Long-Range Financial Planning (2)

The inhibitor of the nuclear factor-kappa B (I kappa B) kinase (IKK) complex is a key regulator of the canonical NF-kappa B signalling cascade and is crucial for fundamental cellular functions, including stress and immune responses. The majority of IKK complex functions are attributed to NF-kappa B activation; however, there is increasing evidence for NF-kappa B pathway-independent signalling. Here we combine quantitative mass spectrometry with random forest bioinformatics to dissect the TNF-alpha-IKK beta-induced phosphoproteome in MCF-7 breast cancer cells. In total, we identify over 20,000 phosphorylation sites, of which similar to 1% are regulated up on TNF-alpha stimulation. We identify various potential novel IKK beta substrates including kinases and regulators of cellular trafficking. Moreover, we show that one of the candidates, AEG-1/MTDH/LYRIC, is directly phosphorylated by IKK beta on serine 298. We provide evidence that IKK beta-mediated AEG-1 phosphorylation is essential for I kappa B alpha degradation as well as NF-kappa B-dependent gene expression and cell proliferation, which correlate with cancer patient survival in vivo

Co-ordination failure, moral hazard and sovereign bankruptcy procedures

We study a model of sovereign debt crisis that combines problems of creditor co-ordination and debtor moral hazard. Solving the sovereign debtor’s incentives leads to excessive ‘rollover failure’ by creditors when sovereign default occurs. We discuss how the incidence of crises might be reduced by international sovereign bankruptcy procedures, involving ‘contractibility’ of sovereign debtor’s payoffs, suspension of convertibility in a ‘discovery’ phase and penalties in case of malfeasance. In relation to the current debate, this is more akin to the IMF’s Sovereign Debt Restructuring Mechanism than the Collective Action Clauses promoted by others

The Triarchic Psychopathy Measure (TriPM): alternative to the PCL-R?

Psychopathic personality disorder is the subject of many research papers and in particular in the context of forensic settings, where its link to risk of future violence has been established. This topic is well examined but there is still considerable debate about the nature of the construct and how psychopathy is measured. Contemporary models such as the triarchic theory (Patrick, Fowles & Krueger, 2009) have been put forward yet the research into psychopathy tends to rely on one assessment tool, the Psychopathy Checklist-Revised (PCL-R; Hare, 2003) that is argued not to capture elements of psychopathy such as boldness. The Triarchic Psychopathy Measure (TriPM; Patrick, 2010) is a measure that is based on the triarchic theory, and it places an equal focus on boldness when measuring psychopathy. It is however a self-report instrument, and this approach has many limitations. This paper aims to review the scientific support for the TriPM and to discuss its potential application to clinical practice. It concludes that the TriPM may not yet be a contender for the PCL-R throne as the sole tool of choice for psychopathy measurement, but the research into the application of the TriPM is expanding our understanding of psychopathy as a construct

Digenic inheritance of mutations in EPHA2 and SLC26A4 in Pendred syndrome

Enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations of the SLC26A4 gene, encoding pendrin, causes non-syndromic hearing loss with EVA or Pendred syndrome, a considerable number of patients appear to carry mono-allelic mutation. This suggests faulty pendrin regulatory machinery results in hearing loss. Here we identify EPHA2 as another causative gene of Pendred syndrome with SLC26A4. EphA2 forms a protein complex with pendrin controlling pendrin localization, which is disrupted in some pathogenic forms of pendrin. Moreover, point mutations leading to amino acid substitution in the EPHA2 gene are identified from patients bearing mono-allelic mutation of SLC26A4. Ephrin-B2 binds to EphA2 triggering internalization with pendrin inducing EphA2 autophosphorylation weakly. The identified EphA2 mutants attenuate ephrin-B2- but not ephrin-A1-induced EphA2 internalization with pendrin. Our results uncover an unexpected role of the Eph/ephrin system in epithelial function

Bioconversion of cassava starch by-product into Bacillus and related bacteria polyhydroxyalkanoates

Background: Unlike petroleum-based synthetic plastics, biodegradable biopolymer generation from industrial residue is a key strategy to reduce costs in the production process, as well as in the waste management, since efficient industrial wastewater treatment could be costly. In this context, the present work describes the prospection and use of bacterial strains capable to bioconvert cassava starch by-product into biodegradable polyhydroxyalkanoates (PHAs). Results: The first step of this study was the bacterial competence screening which was conducted with 72 strains covering 21 Bacillus and related species. The microorganism growth in a medium with a starch substrate was measured by an innovative MTT assay, while the ability of the bacteria to secrete amylase and produce PHA was evaluated by the Nile Red Dye method. Based on growth and potential for PHA production, four isolates were selected and identified as Bacillus megaterium by 16S rRNA sequencing. When cultivated in hydrolyzed cassava starch by-product, maximum production reached 4.97 g dry biomass/L with 29.7% of Poly-(3-hydroxybutyrate) (characterized by FTIR). Conclusions: MTT assay proved to be a reliable methodology for monitoring bacterial growth in insoluble media. Selected amylolytic strains could be used as an alternative industrial process for biodegradable plastics production from starchy residues, reducing costs for biodegradable biopolymer production and wastewater treatment operations