Alveolar macrophages and the diagnosis of drowning

In the present study, we examined the number of alveolar macrophages in lung tissue from 17 cases of fresh water drowning, 22 cases of acute death and 6 cases of lung emphysema. When counting only the number of alveolar macrophages per alveolus without consideration of the alveolar size we found no relevant differences between the groups investigated. To exclude any influence of the alveolar size on the results the surface density of the alveolar macrophages and interstitial tissue was estimated and compared in the different groups. In cases of drowning, the lungs showed significantly lower values in both categories. The ratio of ‘alveolar macrophages/interstitial tissue’ was also reduced in cases of drowning in comparison to the other groups, however, without significant differences. These morphometrical results characterizing the ‘emphysema aquosum’ with almost ‘empty’ and dilated alveoli could be explained by a wash-out effect of the drowning fluid leading to a partial removal of the macrophages from the alveoli. This hypothesis was confirmed by the detection of alveolar macrophages in the drowning froth by immunohistochemical analysis. Even though alveolar macrophages were unambiguously identified in advanced putrefied lungs in HE-stained sections as well as by immunohistochemical staining, an estimation of the number of these cells cannot provide further information for the diagnosis of drowning in putrefied corpses due to the autolytic destruction of the lung architecture providing no reliable values

Generating Performance Portable Code using Rewrite Rules: From High-Level Functional Expressions to High-Performance OpenCL Code

Computers have become increasingly complex with the emergence of heterogeneous hardware combining multicore CPUs and GPUs. These parallel systems exhibit tremendous computational power at the cost of increased programming effort resulting in a tension between performance and code portability. Typically, code is either tuned in a low-level imperative language using hardware-specific optimizations to achieve maximum performance or is written in a high-level, possibly functional, language to achieve portability at the expense of performance. We propose a novel approach aiming to combine high-level programming, code portability, and high-performance. Starting from a high-level functional expression we apply a simple set of rewrite rules to transform it into a low-level functional representation, close to the OpenCL programming model, from which OpenCL code is generated. Our rewrite rules define a space of possible implementations which we automatically explore to generate hardware-specific OpenCL implementations. We formalize our system with a core dependently-typed λ-calculus along with a denotational semantics which we use to prove the correctness of the rewrite rules. We test our design in practice by implementing a compiler which generates high performance imperative OpenCL code. Our experiments show that we can automatically derive hardware-specific implementations from simple functional high-level algorithmic expressions offering performance on a par with highly tuned code for multicore CPUs and GPUs written by experts

Quantum algorithms for algebraic problems

Quantum computers can execute algorithms that dramatically outperform classical computation. As the best-known example, Shor discovered an efficient quantum algorithm for factoring integers, whereas factoring appears to be difficult for classical computers. Understanding what other computational problems can be solved significantly faster using quantum algorithms is one of the major challenges in the theory of quantum computation, and such algorithms motivate the formidable task of building a large-scale quantum computer. This article reviews the current state of quantum algorithms, focusing on algorithms with superpolynomial speedup over classical computation, and in particular, on problems with an algebraic flavor.Comment: 52 pages, 3 figures, to appear in Reviews of Modern Physic

3T3 Cell Lines Stably Expressing Pax6 or Pax6(5a) – A New Tool Used for Identification of Common and Isoform Specific Target Genes

Pax6 and Pax6(5a) are two isoforms of the evolutionary conserved Pax6 gene often co-expressed in specific stochiometric relationship in the brain and the eye during development. The Pax6(5a) protein differs from Pax6 by having a 14 amino acid insert in the paired domain, causing the two proteins to have different DNA binding specificities. Difference in functions during development is proven by the fact that mutations in the 14 amino acid insertion for Pax6(5a) give a slightly different eye phenotype than the one described for Pax6. Whereas quite many Pax6 target genes have been published during the last years, few Pax6(5a) specific target genes have been reported on. However, target genes identified by Pax6 knockout studies can probably be Pax6(5a) targets as well, since this isoform also will be affected by the knockout. In order to identify new Pax6 target genes, and to try to distinguish between genes regulated by Pax6 and Pax6(5a), we generated FlpIn-3T3 cell lines stably expressing Pax6 or Pax6(5a). RNA was harvested from these cell lines and used in gene expression microarrays where we identified a number of genes differentially regulated by Pax6 and Pax6(5a). A majority of these were associated with the extracellular region. By qPCR we verified that Ncam1, Ngef, Sphk1, Dkk3 and Crtap are Pax6(5a) specific target genes, while Tgfbi, Vegfa, EphB2, Klk8 and Edn1 were confirmed as Pax6 specific target genes. Nbl1, Ngfb and seven genes encoding different glycosyl transferases appeared to be regulated by both. Direct binding to the promoters of Crtap, Ctgf, Edn1, Dkk3, Pdgfb and Ngef was verified by ChIP. Furthermore, a change in morphology of the stably transfected Pax6 and Pax6(5a) cells was observed, and the Pax6 expressing cells were shown to have increased proliferation and migration capacities

Multiple Promoters and Alternative Splicing: Hoxa5 Transcriptional Complexity in the Mouse Embryo

The genomic organization of Hox clusters is fundamental for the precise spatio-temporal regulation and the function of each Hox gene, and hence for correct embryo patterning. Multiple overlapping transcriptional units exist at the Hoxa5 locus reflecting the complexity of Hox clustering: a major form of 1.8 kb corresponding to the two characterized exons of the gene and polyadenylated RNA species of 5.0, 9.5 and 11.0 kb. This transcriptional intricacy raises the question of the involvement of the larger transcripts in Hox function and regulation.We have undertaken the molecular characterization of the Hoxa5 larger transcripts. They initiate from two highly conserved distal promoters, one corresponding to the putative Hoxa6 promoter, and a second located nearby Hoxa7. Alternative splicing is also involved in the generation of the different transcripts. No functional polyadenylation sequence was found at the Hoxa6 locus and all larger transcripts use the polyadenylation site of the Hoxa5 gene. Some larger transcripts are potential Hoxa6/Hoxa5 bicistronic units. However, even though all transcripts could produce the genuine 270 a.a. HOXA5 protein, only the 1.8 kb form is translated into the protein, indicative of its essential role in Hoxa5 gene function. The Hoxa6 mutation disrupts the larger transcripts without major phenotypic impact on axial specification in their expression domain. However, Hoxa5-like skeletal anomalies are observed in Hoxa6 mutants and these defects can be explained by the loss of expression of the 1.8 kb transcript. Our data raise the possibility that the larger transcripts may be involved in Hoxa5 gene regulation.Our observation that the Hoxa5 larger transcripts possess a developmentally-regulated expression combined to the increasing sum of data on the role of long noncoding RNAs in transcriptional regulation suggest that the Hoxa5 larger transcripts may participate in the control of Hox gene expression