QBF with Soft Variables

QBF formulae are usually considered in prenex form, i.e. the quantifierblock is completely separated from the propositional part of the QBF.Among others, the semantics of the QBF is defined by the sequence ofthe variables within the prefix, where existentially quantifiedvariables depend on all universally quantified variables stated to theleft.In this paper we extend that classical definition and consider a newquantification type which we call soft variable. The idea is toallow a flexible position and quantifier type for these variables.Hence the type of quantifier of the soft variable can also bealtered. Based on this concept, we present an optimization problemseeking an optimal prefix as defined by user-given preferences. We statean algorithm based on MaxQBF, and present several applications – mainlyfrom verification area – which can be naturally translated into theoptimization problem for QBF with soft variables. We further implementeda prototype solver for this formalism, and compare our approach toprevious work, that differently from ours does not guarantee optimalityand completeness

Bioenergetik und Biochemie bei zerebralen Organoazidopathien am Beispiel der Glutaryl-CoA-Dehydrogenase-Defizienz und der Succinat-Semialdehyd-Dehydrogenase-Defizienz

In der vorliegenden Arbeit wurde die Rolle der Biochemie und Bioenergetik bei zerebralen Organoazidopathien am Beispiel der Glutaryl-CoA-Dehydrogenase (GCDH)-Defizienz und der Succinatsemialdehyd-Dehydrogenase (SSADH)-Defizienz untersucht. Die GCDH-Defizienz ist eine erbliche Stoffwechselstörung im Abbau der Aminosäuren L-Lysin, L-Hydroxylysin und L-Tryptophan. Durch einen Defekt der GCDH akkumulieren bei Patienten Glutaryl-CoA, Glutarsäure (GA) und 3-Hydroxyglutarsäure (3-OH-GA) in Geweben und Körperflüssigkeiten. Unbehandelt wird diese Krankheit in der Kindheit zumeist durch eine striatale Degeneration im Rahmen einer enzephalopathischen Krise nach einer katabolen Stoffwechsellage kompliziert. Die SSADH-Defizienz ist eine erbliche Stoffwechselstörung im Abbau des Neurotransmitters gamma-Aminobuttersäure (GABA). Patienten fallen durch eine Akkumulation von GABA, gamma-Hydroxybuttersäure, Succinatsemialdehyd und 4,5-Dihydroxyhexansäure in Geweben und Körperflüssigkeiten infolge einer defekten SSADH auf. Häufige klinische Befunde sind psychomotorische Retardierung, epileptische Krampfanfälle, Bewegungstörungen und Verhaltensauffälligkeiten. Im bioenergetischen Teil der vorliegenden Arbeit wurde untersucht, ob eine mitochondriale, bioenergetische Dysfunktion an der Pathogenese dieser Erkrankungen beteiligt ist. Hierfür wurden endogene Enzymaktivitäten der Atmungskette und der beta-Oxidation in Gewebehomogenaten von Gcdh- und Ssadh-defizienten Mäusen bestimmt. An isolierten Enzymen, Gewebehomogenaten und submitochondrialen Partikeln wurde der Einfluss der akkumulierenden Metabolite auf die Enzyme der Atmungskette, der beta-Oxidation und des Citratzyklusses getestet. Oxidativer Stress wurde über die Glutathion-Konzentrationen in Gewebehomogenaten abgeschätzt. Das wichtigste Ergebnis für die GCDH-Defizienz war eine unkompetitive Hemmung der alpha-Ketosäure-Dehydrogenase-Komplexe - insbesondere des alpha-Ketoglutarat-Dehydrogenase Komplexes - durch Glutaryl-CoA. Es konnte kein weiterer Einfluss akkumulierender Metabolite auf die Enzyme des Citratzyklusses, der Atmungskette und der beta-Oxidation gefunden werden. Bei Gcdh-defizienten Mäusen waren die endogenen Aktivitäten von Enzymen der beta-Oxidation erniedrigt, die Aktivitäten der Atmungskettenkomplexe waren jedoch unverändert. Für die SSADH-Defizienz konnte keine Änderung endogener Enzymaktivitäten der Atmungskette oder ein direkter Einfluss akkumulierender Metabolite auf die Enzyme der Atmungskette oder des Citratzyklusses gefunden werden. Bei beiden Mausmodellen wurden im Gehirn erniedrigte Glutathion-Konzentrationen als Hinweis auf oxidativen Stress nachgewiesen Die biochemischen Eigenschaften (Gewebeverteilung, Bluthirnschranke [BBB]-Permeabilität und Herkunft der zerebralen Konzentrationen) akkumulierender Metabolite sind für die SSADH-Defizienz gut beschrieben. Obwohl GA und 3-OH-GA postulierte Neurotoxine sind, sind diese Faktoren bei der GCDH-Defizienz noch relativ unbekannt. Deshalb wurden diese biochemischen Eigenschaften für GA und 3-OH-GA untersucht. Hierzu wurden die Konzentrationen dieser Dicarbonsäuren in Gcdh-defizienten (Gcdh-/-) Mäusen, hepatozytären Gcdh-/--Mäusen und C57Bl/6-Mäusen nach einer intraperitonealen Injektion von d4-GA und d5-3-OH-GA gemessen. Zusätzlich wurde der Transport von d4-GA und d5-3-OH-GA über kapilläre Endothelzellen aus Schweinehirn, einem in vitro-Modell der BBB, untersucht. Die wichtigsten Ergebnisse waren wie folgt: 1) ein äquimolarer Anstieg zerebraler und hepatischer GA- und 3-OH-GA-Konzentrationen in Gcdh-/--Mäusen, 2) ein unterschiedlicher Anstieg (Leber >> Gehirn) bei hepatozytären Gcdh-/--Mäusen und C57Bl/6-Mäusen nach einer intraperitonealen Injektion von d4-GA und d5-3-OH-GA und 3) eine geringe Permeabilität der BCEC für GA und 3-OH-GA (Efflux > Influx). Diese Ergebnisse weisen auf eine zerebrale de novo-Synthese von GA und 3-OH-GA und anschließendes Trapping durch eine stark limitierte BBB-Permeabilität für diese Dicarbonsäuren hin

A selectively reduced degree basis for efficient mixed nonlinear isogeometric beam formulations with extensible directors

The effect of higher order continuity in the solution field by using NURBS basis function in isogeometric analysis (IGA) is investigated for an efficient mixed finite element formulation for elastostatic beams. It is based on the Hu-Washizu variational principle considering geometrical and material nonlinearities. Here we present a reduced degree of basis functions for the additional fields of the stress resultants and strains of the beam, which are allowed to be discontinuous across elements. This approach turns out to significantly improve the computational efficiency and the accuracy of the results. We consider a beam formulation with extensible directors, where cross-sectional strains are enriched to avoid Poisson locking by an enhanced assumed strain method. In numerical examples, we show the superior per degree-of-freedom accuracy of IGA over conventional finite element analysis, due to the higher order continuity in the displacement field. We further verify the efficient rotational coupling between beams, as well as the path-independence of the results.Comment: 50 pages, 23 figure

A change of the seaward boundary of Goukamma Marine Protected Area could increase conservation and fishery benefits

Goukamma Marine Protected Area (MPA) on the South African temperate South Coast has been shown to be effective in maintaining a spawning stock of roman, Chrysoblephus laticeps (Sparidae). The larval ecology and the oceanographic conditions in the area suggest a good potential for the enhancement of roman stocks outside the reserve through larval dispersal. A high rate of illegal fishing just inside the seaward boundary of the MPA could severely compromise its function.We suggest that a change of the seaward boundary of the reserve to coincide with a latitudinal line could increase its function as a harvest refuge for resident reef fishes such as roman, facilitate voluntary compliance and monitoring and prosecution of illegal fishing without a significant negative impact on the commercial linefishing fleet in the area. Simple adjustments such as the one proposed here could be attempted at a number of South African MPAs as they would be beneficial to achieve fishery and conservation goals alike

A change of the seaward boundary of Goukamma Marine Protected Area could increase conservation and fishery benefits

Goukamma Marine Protected Area (MPA) on the South African temperate South Coast has been shown to be effective in maintaining a spawning stock of roman, Chrysoblephus laticeps (Sparidae). The larval ecology and the oceanographic conditions in the area suggest a good potential for the enhancement of roman stocks outside the reserve through larval dispersal. A high rate of illegal fishing just inside the seaward boundary of the MPA could severely compromise its function. We suggest that a change of the seaward boundary of the reserve to coincide with a latitudinal line could increase its function as a harvest refuge for resident reef fishes such as roman, facilitate voluntary compliance and monitoring and prosecution of illegal fishing without a significant negative impact on the commercial linefishing fleet in the area. Simple adjustments such as the one proposed here could be attempted at a number of South African MPAs as they would be beneficial to achieve fishery and conservation goals alike

Investigating Cellular Structures at the Nanoscale with Organic Fluorophores

Super-resolution fluorescence imaging can provide insights into cellular structure and organization with a spatial resolution approaching virtually electron microscopy. Among all the different super-resolution methods single-molecule-based localization microscopy could play an exceptional role in the future because it can provide quantitative information, for example, the absolute number of biomolecules interacting in space and time. Here, small organic fluorophores are a decisive factor because they exhibit high fluorescence quantum yields and photostabilities, thus enabling their localization with nanometer precision. Besides past progress, problems with high-density and specific labeling, especially in living cells, and the lack of suited standards and long-term continuous imaging methods with minimal photodamage render the exploitation of the full potential of the method currently challenging

Fundus autofluorescence beyond lipofuscin: lesson learned from ex vivo fluorescence lifetime imaging in porcine eyes

Fundus autofluorescence (FAF) imaging is a well-established method in ophthalmology; however, the fluorophores involved need more clarification. The FAF lifetimes of 20 post mortem porcine eyes were measured in two spectral channels using fluorescence lifetime imaging ophthalmoscopy (FLIO) and compared with clinical data from 44 healthy young subjects. The FAF intensity ratio of the short and the long wavelength emission (spectral ratio) was determined. Ex vivo porcine fundus fluorescence emission is generally less intense than that seen in human eyes. The porcine retina showed significantly (p<0.05) longer lifetimes than the retinal pigment epithelium (RPE): 584 ± 128 ps vs. 121 ± 55 ps 498-560 nm, 240 ± 42 ps vs. 125 ± 20 ps at 560-720 nm. Furthermore, the lifetimes of the porcine RPE were significantly shorter (121 ± 55 ps and 125 ± 20 ps) than those measured from human fundus in vivo (162 ± 14 ps and 179 ± 13 ps, respectively). The fluorescence emission of porcine retina was shifted towards a shorter wavelength compared to that of RPE and human FAF. This data shows the considerable contribution of fluorophores in the neural retina to total FAF intensity in porcine eyes

Effects of cold winters and roost site stability on population development of non-native Asian ring-necked parakeets (Alexandrinus manillensis) in temperate Central Europe – Results of a 16-year census

Asian ring-necked parakeets (Alexandrinus manillensis, formerly Psittacula krameri, hereafter RNP) first bred in&nbsp;Germany in 1969. Since then, RNP numbers increased in all three major German subpopulations (Rhineland,&nbsp;Rhine-Main, Rhine-Neckar) over the period 2003–2018. In the Rhine-Neckar region, the population increased to more than fivefold within only 15 years. Interestingly, there was no significant breeding range expansion of &nbsp;RNP in the period 2010–2018. In 2018, the total number of RNP in Germany amounted to &gt;16,200 birds. Differences&nbsp;in RNP censuses between years were evident. Surprisingly, cold winters (extreme value, −13.7 °C) and&nbsp;cold weather conditions in the breeding season (coldest month average, −1.36 °C) were not able to explain&nbsp;between-year variation. This finding suggests that in general winter mortality is low – with exceptions for winters&nbsp;2008/2009 and 2009/2010, and a population-relevant loss of broods is low in our study population.&nbsp;Surprisingly, the social behaviour in terms of spatio-temporal stability of roost sites could well explain positive and negative population trends. Years of spatially stable and regularly used roost sites seem to correlate with increasing population sizes. In contrast, known shifts of RNP among different roost sites or the formations of&nbsp;new roost sites by split are related to population stagnation or a decrease in numbers. Climate change may lead&nbsp;to further range expansion as cities not suitable yet for RNP may become so in the near future.