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We present XMM-Newton and Chandra observations of the born-again planetary nebula A 30. These X-ray observations reveal a bright unresolved source at the position of the central star whose X-ray luminosity exceeds by far the model expectations for photospheric emission and for shocks within the stellar wind. We suggest that a “born-again hot bubble” may be responsible for this X-ray emission. Diffuse X-ray emission associated with the petal-like features and one of the H-poor knots seen in the optical is also found. The weakened emission of carbon lines in the spectrum of the diffuse emission can be interpreted as the dilution of stellar wind by mass-loading or as the detection of material ejected during a very late thermal pulse.
Background
Riociguat is the first of a new class of drugs, the soluble guanylate cyclase (sGC) stimulators. Riociguat has a dual mode of action: it sensitizes sGC to the body’s own NO and can also increase sGC activity in the absence of NO. The NO-sGC-pathway is impaired in many cardiovascular diseases such as heart failure, pulmonary hypertension and diabetic nephropathy (DN). DN leads to high cardiovascular morbidity and mortality. There is still a high unmet medical need. The urinary albumin excretion rate is a predictive biomarker for these clinical events. Therefore, we investigated the effect of riociguat, alone and in combination with the angiotensin II receptor antagonist (ARB) telmisartan on the progression of DN in diabetic eNOS knock out mice, a new model closely resembling human pathology.
Methods
Seventy-six male eNOS knockout C57BL/6J mice were divided into 4 groups after receiving intraperitoneal high-dose streptozotocin: telmisartan (1 mg/kg), riociguat (3 mg/kg), riociguat+telmisartan (3 and 1 mg/kg), and vehicle. Fourteen mice were used as non-diabetic controls. After 12 weeks, urine and blood were obtained and blood pressure measured. Glucose concentrations were highly increased and similar in all diabetic groups.
Results
Riociguat, alone (105.2 ± 2.5 mmHg; mean±SEM; n = 14) and in combination with telmisartan (105.0 ± 3.2 mmHg; n = 12), significantly reduced blood pressure versus diabetic controls (117.1 ± 2.2 mmHg; n = 14; p = 0.002 and p = 0.004, respectively), whereas telmisartan alone (111.2 ± 2.6 mmHg) showed a modest blood pressure lowering trend (p = 0.071; n = 14). The effects of single treatment with either riociguat (97.1 ± 15.7 µg/d; n = 13) or telmisartan (97.8 ± 26.4 µg/d; n = 14) did not significantly lower albumin excretion on its own (p = 0.067 and p = 0.101, respectively). However, the combined treatment led to significantly lower urinary albumin excretion (47.3 ± 9.6 µg/d; n = 12) compared to diabetic controls (170.8 ± 34.2 µg/d; n = 13; p = 0.004), and reached levels similar to non-diabetic controls (31.4 ± 10.1 µg/d, n = 12).
Conclusion
Riociguat significantly reduced urinary albumin excretion in diabetic eNOS knock out mice that were refractory to treatment with ARB’s alone. Patients with diabetic nephropathy refractory to treatment with ARB’s have the worst prognosis among all patients with diabetic nephropathy. Our data indicate that additional stimulation of sGC on top of standard treatment with ARB`s may offer a new therapeutic approach for patients with diabetic nephropathy resistant to ARB treatment.
Following up on research suggesting an age-related reduction in the rightward extent of the perceptual span during reading (Rayner, Castelhano, & Yang, 2009), we compared old and young adults in an N+2-boundary paradigm in which a nonword preview of word N+2 or word N+2 itself is replaced by the target word once the eyes cross an invisible boundary located after word N. The intermediate word N+1 was always three letters long. Gaze durations on word N+2 were significantly shorter for identical than nonword N+2 preview both for young and for old adults with no significant difference in this preview benefit. Young adults, however, did modulate their gaze duration on word N more strongly than old adults in response to the difficulty of the parafoveal word N+1. Taken together, the results suggest a dissociation of preview benefit and parafoveal-on-foveal effect. Results are discussed in terms of age-related decline in resilience towards distributed processing while simultaneously preserving the ability to integrate parafoveal information into foveal processing. As such, the present results relate to proposals of regulatory compensation strategies older adults use to secure an overall reading speed very similar to that of young adults.
This article presents several acceptability rating experiments concerned with crossing wh-movement in German multiple questions. Our results show that there is no general superiority effect in German, thus refuting claims to the contrary by Featherston (2005). However, acceptability is reduced when a whphrase crosses a wh-subject with which it agrees in animacy. We explain this finding in terms of the availability of different sorting keys for the answers to the multiple questions.
Building biological models by inferring functional dependencies from experimental data is an important issue in Molecular Biology. To relieve the biologist from this traditionally manual process, various approaches have been proposed to increase the degree of automation. However, available approaches often yield a single model only, rely on specific assumptions, and/or use dedicated, heuristic algorithms that are intolerant to changing circumstances or requirements in the view of the rapid progress made in Biotechnology. Our aim is to provide a declarative solution to the problem by appeal to Answer Set Programming (ASP) overcoming these difficulties. We build upon an existing approach to Automatic Network Reconstruction proposed by part of the authors. This approach has firm mathematical foundations and is well suited for ASP due to its combinatorial flavor providing a characterization of all models explaining a set of experiments. The usage of ASP has several benefits over the existing heuristic algorithms. First, it is declarative and thus transparent for biological experts. Second, it is elaboration tolerant and thus allows for an easy exploration and incorporation of biological constraints. Third, it allows for exploring the entire space of possible models. Finally, our approach offers an excellent performance, matching existing, special-purpose systems.
Indirect resource competition and interference are widely occurring mechanisms of interspecific interactions. We have studied the seasonal expression of these two interaction types within a two-species, boreal small mammal system. Seasons differ by resource availability, individual breeding state and intraspecific social system. Live-trapping methods were used to monitor space use and reproduction in 14 experimental populations of bank voles Myodes glareolus in large outdoor enclosures with and without a dominant competitor, the field vole Microtus agrestis. We further compared vole behaviour using staged dyadic encounters in neutral arenas in both seasons. Survival of the non-breeding overwintering bank voles was not affected by competition. In the spring, the numbers of male bank voles, but not of females, were reduced significantly in the competition populations. Bank vole home ranges expanded with vole density in the presence of competitors, indicating food limitation. A comparison of behaviour between seasons based on an analysis of similarity revealed an avoidance of costly aggression against opponents, independent of species. Interactions were more aggressive during the summer than during the winter, and heterospecific encounters were more aggressive than conspecific encounters. Based on these results, we suggest that interaction types and their respective mechanisms are not either–or categories and may change over the seasons. During the winter, energy constraints and thermoregulatory needs decrease direct aggression, but food constraints increase indirect resource competition. Direct interference appears in the summer, probably triggered by each individual’s reproductive and hormonal state and the defence of offspring against conspecific and heterospecific intruders. Both interaction forms overlap in the spring, possibly contributing to spring declines in the numbers of subordinate species.
Preference handling and optimization are indispensable means for addressing nontrivial applications in Answer Set Programming (ASP). However, their implementation becomes difficult whenever they bring about a significant increase in computational complexity. As a consequence, existing ASP systems do not offer complex optimization capacities, supporting, for instance, inclusion-based minimization or Pareto efficiency. Rather, such complex criteria are typically addressed by resorting to dedicated modeling techniques, like saturation. Unlike the ease of common ASP modeling, however, these techniques are rather involved and hardly usable by ASP laymen. We address this problem by developing a general implementation technique by means of meta-prpogramming, thus reusing existing ASP systems to capture various forms of qualitative preferences among answer sets. In this way, complex preferences and optimization capacities become readily available for ASP applications.
Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
We introduce an approach to detecting inconsistencies in large biological networks by using answer set programming. To this end, we build upon a recently proposed notion of consistency between biochemical/genetic reactions and high-throughput profiles of cell activity. We then present an approach based on answer set programming to check the consistency of large-scale data sets. Moreover, we extend this methodology to provide explanations for inconsistencies by determining minimal representations of conflicts. In practice, this can be used to identify unreliable data or to indicate missing reactions.
Background: The ability to create nanostructures with biomolecules is one of the key elements in nanobiotechnology. One of the problems is the expensive and mostly custom made equipment which is needed for their development. We intended to reduce material costs and aimed at miniaturization of the necessary tools that are essential for nanofabrication. Thus we combined the capabilities of molecular ink lithography with DNA-self-assembling capabilities to arrange DNA in an independent array which allows addressing molecules in nanoscale dimensions.
Results: For the construction of DNA based nanostructures a method is presented that allows an arrangement of DNA strands in such a way that they can form a grid that only depends on the spotted pattern of the anchor molecules. An atomic force microscope (AFM) has been used for molecular ink lithography to generate small spots. The sequential spotting process allows the immobilization of several different functional biomolecules with a single AFM-tip. This grid which delivers specific addresses for the prepared DNA-strand serves as a two-dimensional anchor to arrange the sequence according to the pattern. Once the DNA-nanoarray has been formed, it can be functionalized by PNA (peptide nucleic acid) to incorporate advanced structures.
Conclusions: The production of DNA-nanoarrays is a promising task for nanobiotechnology. The described method allows convenient and low cost preparation of nanoarrays. PNA can be used for complex functionalization purposes as well as a structural element.