Correlated Binary Regression Using Orthogonalized Residuals

This paper focuses on marginal regression models for correlated binary responses when estimation of the association structure is of primary interest. A new estimating function approach based on orthogonalized residuals is proposed. This procedure allows a new representation and addresses some of the difficulties of the conditional-residual formulation of alternating logistic regressions of Carey, Zeger & Diggle (1993). The new method is illustrated with an analysis of data on impaired pulmonary function

MAPPING THE SURROUNDINGS AS A REQUIREMENT FOR AUTONOMOUS DRIVING

Motivated by the hype around driverless cars and the challenges of the sensor integration and data processing, this paper presents a model for using a XBox One Microsoft Kinect stereo camera as sensor for mapping the surroundings. Today, the recognition of the environment of the car is mostly done by a mix of sensors like LiDAR, RADAR and cameras. In the case of the outdoor delivery challenge Robotour 2016 with model cars in scale 1:5, it is our goal to solve the task with one camera only. To this end, a three-stage approach was developed. The test results show that our approach can detect and locate objects at a range of up to eight meters in order to incorporate them as barriers in the navigation process

Comparative CRISPR type III-based knockdown of essential genes in hyperthermophilic Sulfolobales and the evasion of lethal gene silencing

CRISPR type III systems, which are abundantly found in archaea, recognize and degrade RNA in their specific response to invading nucleic acids. Therefore, these systems can be harnessed for gene knockdown technologies even in hyperthermophilic archaea to study essential genes. We show here the broader usability of this posttranscriptional silencing technology by expanding the application to further essential genes and systematically analysing and comparing silencing thresholds and escape mutants. Synthetic guide RNAs expressed from miniCRISPR cassettes were used to silence genes involved in cell division (cdvA), transcription (rpo8), and RNA metabolism (smAP2) of the two crenarchaeal model organisms Saccharolobus solfataricus and Sulfolobus acidocaldarius. Results were systematically analysed together with those obtained from earlier experiments of cell wall biogenesis (slaB) and translation (aif5A). Comparison of over 100 individual transformants revealed gene-specific silencing maxima ranging between 40 and 75%, which induced specific knockdown phenotypes leading to growth retardation. Exceedance of this threshold by strong miniCRISPR constructs was not tolerated and led to specific mutation of the silencing miniCRISPR array and phenotypical reversion of cultures. In two thirds of sequenced reverted cultures, the targeting spacers were found to be precisely excised from the miniCRISPR array, indicating a still hypothetical, but highly active recombination system acting on the dynamics of CRISPR spacer arrays. Our results indicate that CRISPR type III - based silencing is a broadly applicable tool to study in vivo functions of essential genes in Sulfolobales which underlies a specific mechanism to avoid malignant silencing overdose

Orthogonalized Residuals for Estimation of Marginally Specified Association Parameters in Multivariate Binary Data: Orthogonalized residuals

This paper focuses on marginal regression models for correlated binary responses when estimation of the association structure is of primary interest. A new estimating function approach based on orthogonalized residuals is proposed. A special case of the proposed procedure allows a new representation of the alternating logistic regressions method through marginal residuals. The connections between second-order generalized estimating equations, alternating logistic regressions, pseudo-likelihood and other methods are explored. Eficiency comparisons are presented, with emphasis on variable cluster size and on the role of higher-order assumptions. The new method is illustrated with an analysis of data on impaired pulmonary function

Enhancement of the electronic contribution to the low temperature specific heat of Fe/Cr magnetic multilayer

We measured the low temperature specific heat of a sputtered $(Fe_{23\AA}/Cr_{12\AA})_{33}$ magnetic multilayer, as well as separate $1000\AA$ thick Fe and Cr films. Magnetoresistance and magnetization measurements on the multilayer demonstrated antiparallel coupling between the Fe layers. Using microcalorimeters made in our group, we measured the specific heat for $4<T<30 K$ and in magnetic fields up to $8 T$ for the multilayer. The low temperature electronic specific heat coefficient of the multilayer in the temperature range $4<T<14 K$ is $\gamma_{ML}=8.4 mJ/K^{2}g-at$. This is significantly larger than that measured for the Fe or Cr films (5.4 and $3.5 mJ/K^{2}mol$ respectively). No magnetic field dependence of $\gamma_{ML}$ was observed up to $8 T$. These results can be explained by a softening of the phonon modes observed in the same data and the presence of an Fe-Cr alloy phase at the interfaces.Comment: 20 pages, 5 figure

Whole mitochondrial DNA sequencing in Alpine populations and the genetic history of the Neolithic Tyrolean Iceman

The Tyrolean Iceman is an extraordinarily well-preserved natural mummy that lived south of the Alpine ridge ~5,200 years before present (ybp), during the Copper Age. Despite studies that have investigated his genetic profile, the relation of the Iceman´s maternal lineage with present-day mitochondrial variation remains elusive. Studies of the Iceman have shown that his mitochondrial DNA (mtDNA) belongs to a novel lineage of haplogroup K1 (K1f) not found in extant populations. We analyzed the complete mtDNA sequences of 42 haplogroup K bearing individuals from populations of the Eastern Italian Alps – putatively in genetic continuity with the Tyrolean Iceman—and compared his mitogenome with a large dataset of worldwide K1 sequences. Our results allow a re-definition of the K1 phylogeny and indicate that the K1f haplogroup is absent or rare in present-day populations. We suggest that mtDNA Iceman´s lineage could have disappeared during demographic events starting in Europe from ~5,000 ybp. Based on the comparison of our results with published data, we propose a scenario that could explain the apparent contrast between the phylogeographic features of maternal and paternal lineages of the Tyrolean Iceman within the context of the demographic dynamics happening in Europe from 8,000 ybp.This study was financed by the Provincia Autonoma di Bolzano – Alto Adige, Ripartizione Diritto allo studio, università e ricerca scientifica, funds to VCS

Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions

Altered glucocorticoid receptor (GR) signaling is a postulated mechanism for the pathogenesis of major depression. To mimic the human situation of altered GR function claimed for depression, we generated mouse strains that underexpress or overexpress GR, but maintain the regulatory genetic context controlling the GR gene. To achieve this goal, we used the following: (1) GR-heterozygous mutant mice (GR+/-) with a 50% GR gene dose reduction, and (2) mice overexpressing GR by a yeast artificial chromosome resulting in a twofold gene dose elevation. GR+/- mice exhibit normal baseline behaviors but demonstrate increased helplessness after stress exposure, a behavioral correlate of depression in mice. Similar to depressed patients, GR+/- mice have a disinhibited hypothalamic-pituitary-adrenal (HPA) system and a pathological dexamethasone/corticotropin-releasing hormone test. Thus, they represent a murine depression model with good face and construct validity. Overexpression of GR in mice evokes reduced helplessness after stress exposure, and an enhanced HPA system feedback regulation. Therefore, they may represent a model for a stress-resistant strain. These mouse models can now be used to study biological changes underlying the pathogenesis of depressive disorders. As a first potential molecular correlate for such changes, we identified a downregulation of BDNF protein content in the hippocampus of GR+/- mice, which is in agreement with the so-called neurotrophin hypothesis of depression

The Structure of IR Luminous Galaxies at 100 Microns

We have observed twenty two galaxies at 100 microns with the Kuiper Airborne Observatory in order to determine the size of their FIR emitting regions. Most of these galaxies are luminous far-infrared sources, with L_FIR > 10^11 L_sun. This data constitutes the highest spatial resolution ever achieved on luminous galaxies in the far infrared. Our data includes direct measurements of the spatial structure of the sources, in which we look for departures from point source profiles. Additionally, comparison of our small beam 100 micron fluxes with the large beam IRAS fluxes shows how much flux falls beyond our detectors but within the IRAS beam. Several sources with point- like cores show evidence for such a net flux deficit. We clearly resolved six of these galaxies at 100 microns and have some evidence for extension in seven others. Those galaxies which we have resolved can have little of their 100 micron flux directly emitted by a point-like active galactic nucleus (AGN). Dust heated to ~40 K by recent bursts of non-nuclear star formation provides the best explanation for their extreme FIR luminosity. In a few cases, heating of an extended region by a compact central source is also a plausible option. Assuming the FIR emission we see is from dust, we also use the sizes we derive to find the dust temperatures and optical depths at 100 microns which we translate into an effective visual extinction through the galaxy. Our work shows that studies of the far infrared structure of luminous infrared galaxies is clearly within the capabilities of new generation far infrared instrumentation, such as SOFIA and SIRTF.Comment: 8 tables, 23 figure

AMR, stability and higher accuracy

Efforts to achieve better accuracy in numerical relativity have so far focused either on implementing second order accurate adaptive mesh refinement or on defining higher order accurate differences and update schemes. Here, we argue for the combination, that is a higher order accurate adaptive scheme. This combines the power that adaptive gridding techniques provide to resolve fine scales (in addition to a more efficient use of resources) together with the higher accuracy furnished by higher order schemes when the solution is adequately resolved. To define a convenient higher order adaptive mesh refinement scheme, we discuss a few different modifications of the standard, second order accurate approach of Berger and Oliger. Applying each of these methods to a simple model problem, we find these options have unstable modes. However, a novel approach to dealing with the grid boundaries introduced by the adaptivity appears stable and quite promising for the use of high order operators within an adaptive framework