Substrate Integrated Waveguide Filters based on Even-And Odd-Mode Predistortion Technique

Novel techniques for the design of predistorted Substrate Integrated Waveguide (SIW) bandpass and bandstop filter are presented. The techniques allow for the realization of lossy filters with ideal lossless transmission and reflection response, offset by a constant amount. Two prototype third-degree Chebyshev bandpass and Inverse Chebyshev bandstop filters are proposed and designed. The two SIW filters having the same center frequency of 6.5 GHz and bandwidth of 125 MHz are implemented on RT/Duroid 4350 substrate with thickness of 0.508 mm. Experimental results show excellent agreement with simulated performance. These new class of filters would be useful in microwave systems where the increased insertion loss can be tolerated, such as in a satellite IMU

Miniaturized dielectric waveguide filters

Design techniques for a new class of integrated monolithic high-permittivity ceramic waveguide filters are presented. These filters enable a size reduction of 50% compared to air-filled transverse electromagnetic filters with the same unloaded Q-factor. Designs for Chebyshev and asymmetric generalised Chebyshev filter and a diplexer are presented with experimental results for an 1800 MHz Chebyshev filter and a 1700 MHz generalised Chebyshev filter showing excellent agreement with theory

Targeted expression profiling reveals distinct stages of early canine fibroblast reprogramming are regulated by 2-oxoglutarate hydroxylases

Background: Ectopic expression of a defined set of transcription factors allows the reprogramming of mammalian somatic cells to pluripotency. Despite continuous progress in primate and rodent reprogramming, limited attention has been paid to cell reprogramming in domestic and companion species. Previous studies attempting to reprogram canine cells have mostly assessed a small number of presumptive canine induced pluripotent stem cell (iPSC) lines for generic pluripotency attributes. However, why canine cell reprogramming remains extremely inefficient is poorly understood. Methods: To better characterize the initial steps of pluripotency induction in canine somatic cells, we optimized an experimental system where canine fetal fibroblasts (cFFs) are transduced with the Yamanaka reprogramming factors by Sendai virus vectors. We use quantitative PCR arrays to measure the expression of 80 target genes at various stages of canine cell reprogramming. We ask how cFF reprogramming is influenced by small molecules affecting the epigenomic modification 5-hydroxymethylcytosine, specifically L-ascorbic acid and retinoic acid (AA/RA). Results: We found that the expression and catalytic output of a class of 2-oxoglutarate-dependent (2-OG) hydroxylases, known as ten-eleven translocation (TET) enzymes, can be modulated in canine cells treated with AA/RA. We further show that AA/RA treatment induces TET1 expression and facilitates early canine reprogramming, evidenced by upregulation of epithelial and pluripotency markers. Using a chemical inhibitor of 2-OG hydroxylases, we demonstrate that 2-OG hydroxylase activity regulates the expression of a subset of genes involved in mesenchymal-to-epithelial transition (MET) and pluripotency in early canine reprogramming. We identify a set of transcription factors depleted in maturing reprogramming intermediates compared to pluripotent canine embryonic stem cells. Conclusions: Our findings highlight 2-OG hydroxylases have evolutionarily conserved and divergent functions regulating the early reprogramming of canine somatic cells and show reprogramming conditions can be rationally optimized for the generation of maturing canine iPSC

Inferring copy number and genotype in tumour exome data

Background: Using whole exome sequencing to predict aberrations in tumours is a cost effective alternative to whole genome sequencing, however is predominantly used for variant detection and infrequently utilised for detection of somatic copy number variation. Results: We propose a new method to infer copy number and genotypes using whole exome data from paired tumour/normal samples. Our algorithm uses two Hidden Markov Models to predict copy number and genotypes and computationally resolves polyploidy/aneuploidy, normal cell contamination and signal baseline shift. Our method makes explicit detection on chromosome arm level events, which are commonly found in tumour samples. The methods are combined into a package named ADTEx (Aberration Detection in Tumour Exome). We applied our algorithm to a cohort of 17 in-house generated and 18 TCGA paired ovarian cancer/normal exomes and evaluated the performance by comparing against the copy number variations and genotypes predicted using Affymetrix SNP 6.0 data of the same samples. Further, we carried out a comparison study to show that ADTEx outperformed its competitors in terms of precision and F-measure. Conclusions: Our proposed method, ADTEx, uses both depth of coverage ratios and B allele frequencies calculated from whole exome sequencing data, to predict copy number variations along with their genotypes. ADTEx is implemented as a user friendly software package using Python and R statistical language. Source code and sample data are freely available under GNU license (GPLv3) at http://adtex.sourceforge.net/

A prebiotic galactooligosaccharide mixture reduces severity of hyperpnoea-induced bronchoconstriction and markers of airway inflammation

Gut microbes have a substantial influence on systemic immune function and allergic sensitisation. Manipulation of the gut microbiome through prebiotics may provide a potential strategy to influence the immunopathology of asthma. This study investigated the effects of prebiotic Bimuno-galactooligosaccharide (B-GOS) supplementation on hyperpnoea-induced bronchoconstriction (HIB), a surrogate for exercise-induced bronchoconstriction, and airway inflammation. A total of ten adults with asthma and HIB and eight controls without asthma were randomised to receive 5·5 g/d of either B-GOS or placebo for 3 weeks separated by a 2-week washout period. The peak fall in forced expiratory volume in 1 s (FEV1) following eucapnic voluntary hyperpnoea (EVH) defined HIB severity. Markers of airway inflammation were measured at baseline and after EVH. Pulmonary function remained unchanged in the control group. In the HIB group, the peak post-EVH fall in FEV1 at day 0 (−880 (SD 480) ml) was unchanged after placebo, but was attenuated by 40 % (−940 (SD 460) v. −570 (SD 310) ml, P= 0·004) after B-GOS. In the HIB group, B-GOS reduced baseline chemokine CC ligand 17 (399 (SD 140) v. 323 (SD 144) pg/ml, P =0·005) and TNF-α (2·68 (SD 0·98) v. 2·18 (SD 0·59) pg/ml, P= 0·040) and abolished the EVH-induced 29 % increase in TNF-α. Baseline C-reactive protein was reduced following B-GOS in HIB (2·46 (SD 1·14) v. 1·44 (SD 0·41) mg/l, P=0·015) and control (2·16 (SD 1·02) v. 1·47 (SD 0·33) mg/l, P=0·050) groups. Chemokine CC ligand 11 and fraction of exhaled nitric oxide remained unchanged. B-GOS supplementation attenuated airway hyper-responsiveness with concomitant reductions in markers of airway inflammation associated with HIB

Structure of Tagatose-1,6-bisphosphate Aldolase. Insight into chiral discrimination, mechanism, and specificity of class II aldolases

Tagatose-1,6-bisphosphate aldolase (TBPA) is a tetrameric class II aldolase that catalyzes the reversible condensation of dihydroxyacetone phosphate with glyceraldehyde 3-phosphate to produce tagatose 1,6-bisphosphate. The high resolution (1.45 Å) crystal structure of the Escherichia coli enzyme, encoded by the agaY gene, complexed with phosphoglycolohydroxamate (PGH) has been determined. Two subunits comprise the asymmetric unit, and a crystallographic 2-fold axis generates the functional tetramer. A complex network of hydrogen bonds position side chains in the active site that is occupied by two cations. An unusual Na(+) binding site is created using a interaction with Tyr(183) in addition to five oxygen ligands. The catalytic Zn(2+) is five-coordinate using three histidine nitrogens and two PGH oxygens. Comparisons of TBPA with the related fructose-1,6-bisphosphate aldolase (FBPA) identifies common features with implications for the mechanism. Because the major product of the condensation catalyzed by the enzymes differs in the chirality at a single position, models of FBPA and TBPA with their cognate bisphosphate products provide insight into chiral discrimination by these aldolases. The TBPA active site is more open on one side than FBPA, and this contributes to a less specific enzyme. The availability of more space and a wider range of aldehyde partners used by TBPA together with the highly specific nature of FBPA suggest that TBPA might be a preferred enzyme to modify for use in biotransformation chemistry

Animation or leaflet: Does it make a difference when educating young people about genome sequencing?

Objective: To compare the effectiveness of an animation against two leaflets with and without images, in educating young people about genome sequencing (GS). Methods: An experimental survey with three assessment points (pre- intervention [T1], post – intervention [T2], 6-week follow-up [T3]). Participants (N = 606) were randomly assigned to receive one of three educational interventions; animation (n = 212); leaflet with images (n = 197); or leaflet with text only (n = 197). Measures of objective and subjective knowledge were completed at T1 (N = 606), T2 (N = 606) and T3 (N = 459). Measures of attitudes, intentions and beliefs towards GS and satisfaction with intervention were completed at T2 only. Results: The type of educational intervention young people received had no significant impact on their objective or subjective knowledge at both T2 and T3 (all p > .05), nor did the educational intervention type affect their attitudes, intentions and beliefs towards GS at T2 (p > .05). However, participant satisfaction was significantly higher in the animation group than the leaflet groups (p < .001). Conclusion: Animations and leaflets are both effective ways to deliver genomic education to young people, but the animations lead to higher satisfaction. Practice implications: Different individuals may find different modes of educational resources more accessible than others. Therefore a range of resources should ideally be made available to patients