Smoke Test Planning using Answer Set Programming

Smoke testing is an important method to increase stability and reliability of hardware- gramming, Testing depending systems. Due to concurrent access to the same physical resource and the impracticality of the use of virtualization, smoke testing requires some form of planning. In this paper, we propose to decompose test cases in terms of atomic actions consisting of preconditions and effects. We present a solution based on answer set programming with multi-shot solving that automatically generates short parallel test plans. Experiments suggest that the approach is feasible for non-inherently sequential test cases and scales up to thousands of test cases

Volume Effects on the Glass Transition Dynamics

The role of jamming (steric constraints) and its relationship to the available volume is addressed by examining the effect that certain modifications of a glass-former have on the ratio of its isochoric and isobaric activation enthalpies. This ratio reflects the relative contribution of volume (density) and temperature (thermal energy) to the temperature-dependence of the relaxation times of liquids and polymers. We find that an increase in the available volume confers a stronger volume-dependence to the relaxation dynamics, a result at odds with free volume interpretations of the glass transition.Comment: 9 pages 5 figure

Tissue specific expression of 11BHSD and its effects on plasma corticosterone during the stress response

The hypothalamic-pituitary-adrenal (HPA) axis is under complex regulatory control at multiple levels. Enzymatic regulation plays an important role in both circulating levels and target tissue exposure. Three key enzyme pathways are responsible for the immediate control of glucocorticoids. De novo synthesis of glucocorticoid from cholesterol involves a multistep enzymatic cascade. This cascade terminates with 11β-hydroxylase, responsible for the final conversion of 11 deoxy- precursors into active glucocorticoids. Additionally, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) controls regeneration of glucocorticoids from inactive metabolites, providing a secondary source of active glucocorticoids. Localized inactivation of glucocorticoids is under the control of Type 2 11β-HSD (11β-HSD2). The function of these enzymes is largely unexplored in wild species, particularly songbirds. Here we aim to explore the contribution of both clearance and generation of glucocorticoids to regulation of the hormonal stress response via use of pharmacological antagonists. Additionally, we mapped 11β-HSD gene expression. We found 11β-HSD1 primarily in liver, kidney, and adrenal glands though it was detectable across all tissue types. 11β-HSD2 was predominately expressed in the adrenal glands and kidney with moderate gonadal and liver expression. Inhibition of glucocorticoid generation by metyrapone was found to decrease levels peripherally, while both peripheral and central DETC administration resulted in elevated concentrations of corticosterone. These data suggest that during the stress response, peripheral antagonism of the 11β-HSD system has a greater impact on circulating glucocorticoid levels than central control. Further studies show aim to elucidate the respective roles of the 11β-HSD and 11β-hydroxylase enzymes

Formation and evolution of S0 galaxies: a SAURON case study of NGC7332

We present SAURON integral-field observations of the S0 galaxy NGC7332. Existing broad-band ground-based and HST photometry reveals a double disk structure and a boxy bulge interpreted as a bar viewed close to edge-on. The SAURON two-dimensional stellar kinematic maps confirm the existence of the bar and inner disk but also uncover the presence of a cold counter-rotating stellar component within the central 250 pc. The Hbeta and [OIII] emission line maps show that the ionised gas has a complex morphology and kinematics, including both a component counter-rotating with respect to the stars and a fainter co-rotating one. Analysis of the absorption line-strength maps show that NGC7332 is young everywhere. The presence of a large-scale bar can explain most of those properties, but the fact that we see a significant amount of unsettled gas, together with a few peculiar features in the maps, suggest that NGC7332 is still evolving. Interactions as well as bar-driven processes must thus have played an important role in the formation and evolution of NGC7332, and presumably of S0 galaxies in general.Comment: 12 pages, 12 figures, accepted for publication in MNRA

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Enhanced Membrane Pore Formation through High-Affinity Targeted Antimicrobial Peptides

Many cationic antimicrobial peptides (AMPs) target the unique lipid composition of the prokaryotic cell membrane. However, the micromolar activities common for these peptides are considered weak in comparison to nisin, which follows a targeted, pore-forming mode of action. Here we show that AMPs can be modified with a high-affinity targeting module, which enables membrane permeabilization at low concentration. Magainin 2 and a truncated peptide analog were conjugated to vancomycin using click chemistry, and could be directed towards specific membrane embedded receptors both in model membrane systems and whole cells. Compared with untargeted vesicles, a gain in permeabilization efficacy of two orders of magnitude was reached with large unilamellar vesicles that included lipid II, the target of vancomycin. The truncated vancomycin-peptide conjugate showed an increased activity against vancomycin resistant Enterococci, whereas the full-length conjugate was more active against a targeted eukaryotic cell model: lipid II containing erythrocytes. This study highlights that AMPs can be made more selective and more potent against biological membranes that contain structures that can be targeted

Stellar Kinematics and Populations of Early-Type Galaxies with the SAURON and OASIS Integral-Field Spectrographs

We summarise the results and achievements of integral-field spectroscopy of early-type galaxies, observed as part of a survey using both the SAURON and OASIS spectrographs. From the perspective of integral-field spectroscopy, these otherwise smooth and featureless objects show a wealth of structure, both in their stellar kinematics and populations. We focus on the stellar content, and examine properties on both kiloparsec scales with SAURON, and scales of 100's of parsecs with OASIS. These complementary studies reveal two types of kinematically distinct components (KDCs), differing primarily in their intrinsic sizes. In previous studies, KDCs and their host galaxies have generally been found to be unremarkable in other aspects. We show that large KDCs, typical of the well-studied cases, indeed show little or no age differences with their host galaxy. The KDCs detected with the higher spatial-resolution of OASIS are intrinsically smaller and include, in contrast, a significant fraction of young stars. We speculate on the relationship between KDCs and their host galaxies, and the implications for young populations in early-type galaxies.Comment: 20 pages, 6 figures. Invited talk, submitted to "Adaptive Optics-Assisted Integral-Field Spectroscopy", Rutten R.G.M., Benn C.R., Mendez J., eds., May 2005, La Palma (Spain), New Astr. Rev. For full resolution PS, see http://www.strw.leidenuniv.nl/~mcdermid/mcdermid_ao_workshop_20050830.ps.g

Exploring the genetics of lithium response in bipolar disorders

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II

The human keratins: biology and pathology

The keratins are the typical intermediate filament proteins of epithelia, showing an outstanding degree of molecular diversity. Heteropolymeric filaments are formed by pairing of type I and type II molecules. In humans 54 functional keratin genes exist. They are expressed in highly specific patterns related to the epithelial type and stage of cellular differentiation. About half of all keratins—including numerous keratins characterized only recently—are restricted to the various compartments of hair follicles. As part of the epithelial cytoskeleton, keratins are important for the mechanical stability and integrity of epithelial cells and tissues. Moreover, some keratins also have regulatory functions and are involved in intracellular signaling pathways, e.g. protection from stress, wound healing, and apoptosis. Applying the new consensus nomenclature, this article summarizes, for all human keratins, their cell type and tissue distribution and their functional significance in relation to transgenic mouse models and human hereditary keratin diseases. Furthermore, since keratins also exhibit characteristic expression patterns in human tumors, several of them (notably K5, K7, K8/K18, K19, and K20) have great importance in immunohistochemical tumor diagnosis of carcinomas, in particular of unclear metastases and in precise classification and subtyping. Future research might open further fields of clinical application for this remarkable protein family