Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

In-cylinder Temperature Measurements in a 55-cm\u3csup\u3e3\u3c/sup\u3e Two Stroke Engine via Tunable Laser Absorption Spectroscopy

In-cylinder temperature is a critical quantity for modelling and understanding combustion dynamics in internal combustion engines. It is difficult to measure in small, two-stroke engines due to high operational speeds and limited space to install instrumentation. Optical access was established in a 55 cm3 displacement two-stroke engine using M4 bolts as carriers for sapphire rods to establish a 1.5 mm diameter optical path through the combustion chamber. Temperature Laser Absorption Spectroscopy was successfully used to measure time varying in-cylinder temperature clocked to the piston position with a resolution of 3.6 crank angle degrees at 6000 rpm. The resulting temperature profiles clearly showed the traverse of the flame front and were qualitatively consistent with in-cylinder pressure, engine speed, and delivery ratio. The temperature measurements were compared to aggregate in-cylinder temperatures calculated using the ideal gas model using measured in-cylinder pressure and trapped mass calculated at exact port closure as inputs. The calculation was sensitive to the trapped mass determination, and the results show that using the ideal gas model for in-cylinder temperature calculations in heat flux models may fail to capture trends in actual in-cylinder temperature with changing engine operating conditions