Fundamental bounds on transmission through periodically perforated metal screens with experimental validation

This paper presents a study of transmission through arrays of periodic sub-wavelength apertures. Fundamental limitations for this phenomenon are formulated as a sum rule, relating the transmission coefficient over a bandwidth to the static polarizability. The sum rule is rigorously derived for arbitrary periodic apertures in thin screens. By this sum rule we establish a physical bound on the transmission bandwidth which is verified numerically for a number of aperture array designs. We utilize the sum rule to design and optimize sub-wavelength frequency selective surfaces with a bandwidth close to the physically attainable. Finally, we verify the sum rule and simulations by measurements of an array of horseshoe-shaped slots milled in aluminum foil.Comment: 10 pages, 11 figures. Updated Introduction and Conclusion

Single molecule analysis of combinatorial splicing

Alternative splicing creates diverse mRNA isoforms from single genes and thereby enhances complexity of transcript structure and of gene function. We describe a method called spliceotyping, which translates combinatorial mRNA splicing patterns along transcripts into a library of binary strings of nucleic acid tags that encode the exon composition of individual mRNA molecules. The exon inclusion pattern of each analyzed transcript is thus represented as binary data, and the abundance of different splice variants is registered by counts of individual molecules. The technique is illustrated in a model experiment by analyzing the splicing patterns of the adenovirus early 1A gene and the beta actin reference transcript. The method permits many genes to be analyzed in parallel and it will be valuable for elucidating the complex effects of combinatorial splicing

A dual-tag microarray platform for high-performance nucleic acid and protein analyses

DNA microarrays serve to monitor a wide range of molecular events, but emerging applications like measurements of weakly expressed genes or of proteins and their interaction patterns will require enhanced performance to improve specificity of detection and dynamic range. To further extend the utility of DNA microarray-based approaches we present a high-performance tag microarray procedure that enables probe-based analysis of as little as 100 target cDNA molecules, and with a linear dynamic range close to 105. Furthermore, the protocol radically decreases the risk of cross-hybridization on microarrays compared to current approaches, and it also allows for quantification by single-molecule analysis and real-time on-chip monitoring of rolling-circle amplification. We provide proof of concept for microarray-based measurement of both mRNA molecules and of proteins, converted to tag DNA sequences by padlock and proximity probe ligation, respectively

Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

<p>Abstract</p> <p>Background</p> <p>Familial adenomatous polyposis (FAP) is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the <it>APC </it>gene mutation, possible genotype-phenotype correlations largely remain to be defined for the extracolonic manifestations.</p> <p>Methods</p> <p>Full genomic sequencing combined with multiplex ligation-dependent probe amplification was used to identify <it>APC </it>gene mutations, which were correlated to the clinical presentations.</p> <p>Results</p> <p>10 novel <it>APC </it>gene mutations were identified in 11 families. A broad spectrum of extracolonic manifestations was identified in most of these individuals. Two sisters with an insertion in codon 528 (c.1582_1583insGC) both showed severe phenotypes with classical polyposis, upper gastrointestinal polyps and thyroid cancer. A woman with a 3'<it>APC </it>mutation (c.5030_5031insAA) developed colon cancer at age 72 as the first manifestation of attenuated FAP.</p> <p>Conclusion</p> <p>With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel <it>APC </it>mutations and present two FAP cases that suggest familial aggregation of thyroid cancer and demonstrate the need to consider attenuated FAP also among elderly patients with colon cancer.</p

Targeted resequencing of candidate genes using selector probes

Targeted genome enrichment is a powerful tool for making use of the massive throughput of novel DNA-sequencing instruments. We herein present a simple and scalable protocol for multiplex amplification of target regions based on the Selector technique. The updated version exhibits improved coverage and compatibility with next-generation-sequencing (NGS) library-construction procedures for shotgun sequencing with NGS platforms. To demonstrate the performance of the technique, all 501 exons from 28 genes frequently involved in cancer were enriched for and sequenced in specimens derived from cell lines and tumor biopsies. DNA from both fresh frozen and formalin-fixed paraffin-embedded biopsies were analyzed and 94% specificity and 98% coverage of the targeted region was achieved. Reproducibility between replicates was high (R2 = 0, 98) and readily enabled detection of copy-number variations. The procedure can be carried out in <24 h and does not require any dedicated instrumentation

ProteinSeq: High-Performance Proteomic Analyses by Proximity Ligation and Next Generation Sequencing

Despite intense interest, methods that provide enhanced sensitivity and specificity in parallel measurements of candidate protein biomarkers in numerous samples have been lacking. We present herein a multiplex proximity ligation assay with readout via realtime PCR or DNA sequencing (ProteinSeq). We demonstrate improved sensitivity over conventional sandwich assays for simultaneous analysis of sets of 35 proteins in 5 µl of blood plasma. Importantly, we observe a minimal tendency to increased background with multiplexing, compared to a sandwich assay, suggesting that higher levels of multiplexing are possible. We used ProteinSeq to analyze proteins in plasma samples from cardiovascular disease (CVD) patient cohorts and matched controls. Three proteins, namely P-selectin, Cystatin-B and Kallikrein-6, were identified as putative diagnostic biomarkers for CVD. The latter two have not been previously reported in the literature and their potential roles must be validated in larger patient cohorts. We conclude that ProteinSeq is promising for screening large numbers of proteins and samples while the technology can provide a much-needed platform for validation of diagnostic markers in biobank samples and in clinical use

Utvecklingssamtal i grupp - En studie i några kommunala verksamheter

Syftet med studien är att undersöka hur samtalsledare och medarbetare upplever utvecklingssamtal i grupp jämfört med individuella utvecklingssamtal. Den har genomförts med hjälp av semistrukturerade intervjuer i några olika kommunala verksamheter och visar att deltagarna upplever skillnader mellan de olika samtalsmetoderna och att olika frågor behandlas i respektive samtal. De är positiva till utvecklingssamtal i grupp men anser samtidigt att de individuella utvecklingssamtalen inte helt kan ersättas av utvecklingssamtal i grupp. Individuella utvecklingssamtal, mellan chefen och den anställde, ska vara personliga och handla om individen medan grupputvecklingssamtal handlar om verksamheten, arbetsmiljön, målen och arbetsrelaterade frågor. Att känna trygghet i gruppen framhålls som viktig för att kunna genomföra utvecklingssamtal i grupp

Fatigue Strength of Friction Stir Welded Joints in Aluminium

Solid state Friction stir welding (FSW) is of major interest in the welding of aluminium since it improves the joint properties. Many applications where Al-alloys are used are subject to varying load conditions, making fatigue failure a critical issue. In the scope of this thesis, the fatigue performance of friction stir welded AlMgSi-alloy 6082 has been investigated. Static and dynamic properties of different joint configurations and welds produced with varying process parameters have been determined. Microstructures of fractured surfaces have been studied to evaluate the effect of weld discontinuities on fatigue. The mechanical strength of the friction stir welds was set in relation to that of conventional fusion welds, and that of other FS welded Al-alloys. The friction stir process produced aluminium butt welds with high and consistent fatigue strengths, which exceeded the strengths of similar fusion welded samples. A smooth weld geometry showed to be of great importance for the fatigue performance, favouring the friction stir welds. Welding speed in a tested range of 0.35-1.4 m/min had only a modest influence on the properties of the friction stir welds; properties were not deteriorating at the highest speed. The softening of the alloy around the weldline was modelled. A fair description of the hardness profiles across the weld was obtained. At a low and high welding speed a full and partial softening respectively was predicted, indicating that full softening is not required to obtain a flawless weld. In case of friction stir overlap welds, tool design is even more important than in butt welding to secure weld quality. A broad tool shoulder with a concave pin end gave the best performance. In particular, the minimal influence on the sheet interface when welding with such a tool was beneficial for the fatigue strength. The stress distribution in overlap and T-type test specimens has been modelled. The stress intensity factors were determined. The corresponding crack propagation rates were in fair accordance with the experimental results. It was found that a simplified approach, developed to estimate ∆K for overlap spot welds, could be used also for friction stir overlap joints.QC 2010100

Fatigue Strength of Friction Stir Welded Joints in Aluminium

Solid state Friction stir welding (FSW) is of major interest in the welding of aluminium since it improves the joint properties. Many applications where Al-alloys are used are subject to varying load conditions, making fatigue failure a critical issue. In the scope of this thesis, the fatigue performance of friction stir welded AlMgSi-alloy 6082 has been investigated. Static and dynamic properties of different joint configurations and welds produced with varying process parameters have been determined. Microstructures of fractured surfaces have been studied to evaluate the effect of weld discontinuities on fatigue. The mechanical strength of the friction stir welds was set in relation to that of conventional fusion welds, and that of other FS welded Al-alloys. The friction stir process produced aluminium butt welds with high and consistent fatigue strengths, which exceeded the strengths of similar fusion welded samples. A smooth weld geometry showed to be of great importance for the fatigue performance, favouring the friction stir welds. Welding speed in a tested range of 0.35-1.4 m/min had only a modest influence on the properties of the friction stir welds; properties were not deteriorating at the highest speed. The softening of the alloy around the weldline was modelled. A fair description of the hardness profiles across the weld was obtained. At a low and high welding speed a full and partial softening respectively was predicted, indicating that full softening is not required to obtain a flawless weld. In case of friction stir overlap welds, tool design is even more important than in butt welding to secure weld quality. A broad tool shoulder with a concave pin end gave the best performance. In particular, the minimal influence on the sheet interface when welding with such a tool was beneficial for the fatigue strength. The stress distribution in overlap and T-type test specimens has been modelled. The stress intensity factors were determined. The corresponding crack propagation rates were in fair accordance with the experimental results. It was found that a simplified approach, developed to estimate ∆K for overlap spot welds, could be used also for friction stir overlap joints.QC 2010100