Puente sobre el tramo inferior del Elba, Hamburgo

This bridge joins to Hamburg-Hannover and the Hamburg-Lübeck roadways. It is 411 m long, 30.74 m wide, and has five spans. The main span is 172 m long, and is suspended by cables from two towers, rising 53 m above the bridge pavement. The stiffening; structure of this suspended span consists of a central box and two lateral full web girders, with a uniform depth of 2 ms. The towers support two sets of cables, which rest on supports situated at unequal heights with respect to each other. These supports are so arranged that thermal deformations shall not be excessive nor cause large secondary moments. Most of the bridge elements have been manufactured in the workshops and taken to the site by river transport. The main span has been built by successive overhangs, till the two sides have met together at the crown.Este puente, que une las autopistas Hamburgo-Hannover y Hamburgo-Lübeck, tiene 411 m de longitud, 30,74 m de anchura y 5 tramos. El entramado de rigidez del tramo central, de 173 m de luz, que está suspendido por cables que se apoyan en dos torres, de 53 m de altura respecto a la calzada, tiene la sección transversal formada por un cajón central y dos vigas laterales de alma llena con un canto uniforme de 3 m. Dichas torres soportan dos paquetes de cables que se apoyan en sillas montadas a diferente altura, estando estos apoyos organizados de forma que permitan los movimientos provocados por las diferencias de temperatura sin originar deformaciones abusivas ni momentos secundarios. La mayor parte de los elementos han sido prefabricados en taller y transportados por vía fluvial. La construcción del tramo central se ha realizado por voladizos sucesivos hasta llegar al cierre en la clave

Expression profiling of human donor lungs to understand primary graft dysfunction after lung transplantation

Lung transplantation is the treatment of choice for end-stage pulmonary diseases. A limited donor supply has resulted in 4000 patients on the waiting list. Currently, 10-20% of donor organs offered for transplantation are deemed suitable under the selection criteria, of which 15-25% fails due to primary graft dysfunction (PGD). This has resulted in increased efforts to search for alternative donor lungs selection criteria. In this study, we attempt to further our understanding of PGD by observing the changes in gene expression across donor lungs that developed PGD versus those that did not. Our second goal is to use a machine learning tool - support vector machine (SVM), to distinguish unsuitable donor lungs from suitable donor lungs, based on the gene expression data. From our analysis, we have obtained transcripts that were involved in signalling, apoptosis and stress-activated pathways. Results also indicate that metallothionein 3 may prevent lungs from developing PGD. Preliminary classification results for distinguishing suitable and unsuitable lungs for transplantation using a SVM were promising. This is the first such attempt to use human lungs used for transplantation and combine the identification of a molecular signature for PGD, with machine learning methods for donor lung prediction

Disease variants in genomes of 44 centenarians

To identify previously reported disease mutations that are compatible with extraordinary longevity, we screened the coding regions of the genomes of 44 Ashkenazi Jewish centenarians. Individual genome sequences were generated with 30x coverage on the Illumina HiSeq 2000 and single-nucleotide variants were called with the genome analysis toolkit (GATK). We identified 130 coding variants that were annotated as pathogenic or likely pathogenic based on the ClinVar database and that are infrequent in the general population. These variants were previously reported to cause a wide range of degenerative, neoplastic, and cardiac diseases with autosomal dominant, autosomal recessive, and X-linked inheritance. Several of these variants are located in genes that harbor actionable incidental findings, according to the recommendations of the American College of Medical Genetics. In addition, we found risk variants for late-onset neurodegenerative diseases, such as the APOE epsilon4 allele that was even present in a homozygous state in one centenarian who did not develop Alzheimer\u27s disease. Our data demonstrate that the incidental finding of certain reported disease variants in an individual genome may not preclude an extraordinarily long life. When the observed variants are encountered in the context of clinical sequencing, it is thus important to exercise caution in justifying clinical decisions

Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivity.

Allergic contact hypersensitivity (CHS) is a T cell-mediated inflammatory skin disease. Interleukin (IL)-12 is considered to be important in the generation of the allergen-specific T cell response. Loss of IL-12 function in IL-12Rbeta2-deficient mice, however, did not ameliorate the allergic immune response, suggesting alternate IL-12-independent pathways in the induction of CHS. Because exposure to contact allergens always takes place in the presence of microbial skin flora, we investigated the potential role of Toll-like receptors (TLRs) in the induction of CHS. Using mice deficient in TLR4, the receptor for bacterial lipopolysaccharide (LPS), IL-12 receptor (R) beta2, or both, we show that the concomitant absence of TLR4 and IL-12Rbeta2, but not the absence of TLR4 or IL-12Rbeta2 alone, prevented DC-mediated sensitization, generation of effector T cells, and the subsequent CHS response to 2,4,6-trinitro-1-chlorobenzene (TNCB), oxazolone, and fluorescein isothiocyanate. Introduction of the TLR4 transgene into the TLR4/IL-12Rbeta2 mutant restored the CHS inducibility, showing a requirement for TLR4 in IL-12-independent CHS induction. Furthermore, the concomitant absence of TLR2 and TLR4 prevented the induction of CHS to TNCB in IL-12-competent mice. Finally, CHS was inducible in germ-free wild-type and IL-12Rbeta2-deficient mice, but not in germ-free TLR4/IL-12Rbeta2 double deficient mice, suggesting that the necessary TLR activation may proceed via endogenous ligands

Current versus flux in the control of electromechanical valve actuators

Abstract-Due to a lack of bandwidth separation, it is unclear which combination of feedback signals would be most advantageous for controlling electromechanical valve actuators. To address this issue, this paper investigates the use of position, current, and flux measurements in the feedback. Based on the analysis, a combination of position and flux best achieves the design specifications without incurring large control signals

A Simple Method for Analyzing Exome Sequencing Data Shows Distinct Levels of Nonsynonymous Variation for Human Immune and Nervous System Genes

To measure the strength of natural selection that acts upon single nucleotide variants (SNVs) in a set of human genes, we calculate the ratio between nonsynonymous SNVs (nsSNVs) per nonsynonymous site and synonymous SNVs (sSNVs) per synonymous site. We transform this ratio with a respective factor f that corrects for the bias of synonymous sites towards transitions in the genetic code and different mutation rates for transitions and transversions. This method approximates the relative density of nsSNVs (rdnsv) in comparison with the neutral expectation as inferred from the density of sSNVs. Using SNVs from a diploid genome and 200 exomes, we apply our method to immune system genes (ISGs), nervous system genes (NSGs), randomly sampled genes (RSGs), and gene ontology annotated genes. The estimate of rdnsv in an individual exome is around 20% for NSGs and 30–40% for ISGs and RSGs. This smaller rdnsv of NSGs indicates overall stronger purifying selection. To quantify the relative shift of nsSNVs towards rare variants, we next fit a linear regression model to the estimates of rdnsv over different SNV allele frequency bins. The obtained regression models show a negative slope for NSGs, ISGs and RSGs, supporting an influence of purifying selection on the frequency spectrum of segregating nsSNVs. The y-intercept of the model predicts rdnsv for an allele frequency close to 0. This parameter can be interpreted as the proportion of nonsynonymous sites where mutations are tolerated to segregate with an allele frequency notably greater than 0 in the population, given the performed normalization of the observed nsSNV to sSNV ratio. A smaller y-intercept is displayed by NSGs, indicating more nonsynonymous sites under strong negative selection. This predicts more monogenically inherited or de-novo mutation diseases that affect the nervous system

Epitaxial growth and anisotropy of La(O,F)FeAs thin films deposited by Pulsed Laser Deposition

LaFeAsO1-xFx thin films were deposited successfully on (001)-oriented LaAlO3 and MgO substrates from stoichiometric LaFeAsO1-xFx polycrystalline targets with fluorine concentrations up to x = 0.25 by PLD. Room temperature deposition and post annealing of the films yield nearly phase pure films with a pronounced c-axis texture and a strong biaxial in-plane orientation. Transport measurements show metallic resistance and onset of superconductivity at 11 K. Hc2(T) was determined by resistive measurements and yield Hc2 values of 3 T at 3.6 K for B||c and 6 T at 6.4 K for B||ab.Comment: 11 pages, 5 figure

Eureka and beyond: mining's impact on African urbanisation

This collection brings separate literatures on mining and urbanisation together at a time when both artisanal and large-scale mining are expanding in many African economies. While much has been written about contestation over land and mineral rights, the impact of mining on settlement, notably its catalytic and fluctuating effects on migration and urban growth, has been largely ignored. African nation-states’ urbanisation trends have shown considerable variation over the past half century. The current surge in ‘new’ mining countries and the slow-down in ‘old’ mining countries are generating some remarkable settlement patterns and welfare outcomes. Presently, the African continent is a laboratory of national mining experiences. This special issue on African mining and urbanisation encompasses a wide cross-section of country case studies: beginning with the historical experiences of mining in Southern Africa (South Africa, Zambia, Zimbabwe), followed by more recent mineralizing trends in comparatively new mineral-producing countries (Tanzania) and an established West African gold producer (Ghana), before turning to the influence of conflict minerals (Angola, the Democratic Republic of Congo and Sierra Leone)