Suppressed phase variations in a high amplitude rapidly oscillating Ap star pulsating in a distorted quadrupole mode

We present the results of a multisite photometric observing campaign on the rapidly oscillating Ap (roAp) star 2MASS 16400299-0737293 (J1640; $V=12.7$). We analyse photometric $B$ data to show the star pulsates at a frequency of $151.93$ d$^{-1}$ ($1758.45 \mu$Hz; $P=9.5$ min) with a peak-to-peak amplitude of 20.68 mmag, making it one of the highest amplitude roAp stars. No further pulsation modes are detected. The stellar rotation period is measured at $3.6747\pm0.0005$ d, and we show that rotational modulation due to spots is in anti-phase between broadband and $B$ observations. Analysis and modelling of the pulsation reveals this star to be pulsating in a distorted quadrupole mode, but with a strong spherically symmetric component. The pulsational phase variation in this star is suppressed, leading to the conclusion that the contribution of $\ell>2$ components dictate the shape of phase variations in roAp stars that pulsate in quadrupole modes. This is only the fourth time such a strong pulsation phase suppression has been observed, leading us to question the mechanisms at work in these stars. We classify J1640 as an A7 Vp SrEu(Cr) star through analysis of classification resolution spectra

Benzyne in V4334 Sqr: A Quest for the Ring with SOFIA/EXES

Large aromatic molecules are ubiquitous in both circumstellar and interstellar environments. Detection of small aromatic molecules, such as benzene (C6H6) and benzyne (C6H4), are rare in astrophysical environments. Detection of such species will have major implications for our understanding of the astrochemistry involved in the formation of the molecules necessary for life, including modeling the chemical pathways to the formation of larger hydrocarbon molecules. We conducted a search for the infrared 18 μm spectral signature of benzyne in V4334 Sgr with the Stratospheric Observatory for Infrared Astronomy (SOFIA)/Echelon-Cross-Echelle Spectrograph (EXES) finding no evidence for a feature at the sensitivity of our observations

Algorithms for optimizing drug therapy

BACKGROUND: Drug therapy has become increasingly efficient, with more drugs available for treatment of an ever-growing number of conditions. Yet, drug use is reported to be sub optimal in several aspects, such as dosage, patient's adherence and outcome of therapy. The aim of the current study was to investigate the possibility to optimize drug therapy using computer programs, available on the Internet. METHODS: One hundred and ten officially endorsed text documents, published between 1996 and 2004, containing guidelines for drug therapy in 246 disorders, were analyzed with regard to information about patient-, disease- and drug-related factors and relationships between these factors. This information was used to construct algorithms for identifying optimum treatment in each of the studied disorders. These algorithms were categorized in order to define as few models as possible that still could accommodate the identified factors and the relationships between them. The resulting program prototypes were implemented in HTML (user interface) and JavaScript (program logic). RESULTS: Three types of algorithms were sufficient for the intended purpose. The simplest type is a list of factors, each of which implies that the particular patient should or should not receive treatment. This is adequate in situations where only one treatment exists. The second type, a more elaborate model, is required when treatment can by provided using drugs from different pharmacological classes and the selection of drug class is dependent on patient characteristics. An easily implemented set of if-then statements was able to manage the identified information in such instances. The third type was needed in the few situations where the selection and dosage of drugs were depending on the degree to which one or more patient-specific factors were present. In these cases the implementation of an established decision model based on fuzzy sets was required. Computer programs based on one of these three models could be constructed regarding all but one of the studied disorders. The single exception was depression, where reliable relationships between patient characteristics, drug classes and outcome of therapy remain to be defined. CONCLUSION: Algorithms for optimizing drug therapy can, with presumably rare exceptions, be developed for any disorder, using standard Internet programming methods

Transkingdom Networks: A Systems Biology Approach to Identify Causal Members of Host-Microbiota Interactions

Improvements in sequencing technologies and reduced experimental costs have resulted in a vast number of studies generating high-throughput data. Although the number of methods to analyze these "omics" data has also increased, computational complexity and lack of documentation hinder researchers from analyzing their high-throughput data to its true potential. In this chapter we detail our data-driven, transkingdom network (TransNet) analysis protocol to integrate and interrogate multi-omics data. This systems biology approach has allowed us to successfully identify important causal relationships between different taxonomic kingdoms (e.g. mammals and microbes) using diverse types of data

Parametric study of EEG sensitivity to phase noise during face processing

<b>Background: </b> The present paper examines the visual processing speed of complex objects, here faces, by mapping the relationship between object physical properties and single-trial brain responses. Measuring visual processing speed is challenging because uncontrolled physical differences that co-vary with object categories might affect brain measurements, thus biasing our speed estimates. Recently, we demonstrated that early event-related potential (ERP) differences between faces and objects are preserved even when images differ only in phase information, and amplitude spectra are equated across image categories. Here, we use a parametric design to study how early ERP to faces are shaped by phase information. Subjects performed a two-alternative force choice discrimination between two faces (Experiment 1) or textures (two control experiments). All stimuli had the same amplitude spectrum and were presented at 11 phase noise levels, varying from 0% to 100% in 10% increments, using a linear phase interpolation technique. Single-trial ERP data from each subject were analysed using a multiple linear regression model. <b>Results: </b> Our results show that sensitivity to phase noise in faces emerges progressively in a short time window between the P1 and the N170 ERP visual components. The sensitivity to phase noise starts at about 120–130 ms after stimulus onset and continues for another 25–40 ms. This result was robust both within and across subjects. A control experiment using pink noise textures, which had the same second-order statistics as the faces used in Experiment 1, demonstrated that the sensitivity to phase noise observed for faces cannot be explained by the presence of global image structure alone. A second control experiment used wavelet textures that were matched to the face stimuli in terms of second- and higher-order image statistics. Results from this experiment suggest that higher-order statistics of faces are necessary but not sufficient to obtain the sensitivity to phase noise function observed in response to faces. <b>Conclusion: </b> Our results constitute the first quantitative assessment of the time course of phase information processing by the human visual brain. We interpret our results in a framework that focuses on image statistics and single-trial analyses

The politics of protest in newspaper campaigns: dissent, populism and the rhetoric of authenticity

Newspaper campaigns embody newspaper’ most emphatic claims to speak for ‘the people’, and as such are generally regarded as populist. However, they can be oppositional, engaging in dissent of one sort or another, and often assume a certain amount of political engagement with that dissent on the part of the audience. This article examines the potential of newspaper camapigns to facilitate the political engagement of citizens through the politics of protest. It draws on qualitative analysis of seven campaigns that ran in the Scottish press between 2000 and 2005, and semi-structured interviews with relevant journalists. The distinction between legitimate protest and manipulative populism is made in terms of: (a) the rhetoric and strategies of political representation, participation and influence and (b) the construction of political legitimacy in terms of the public interest and the moral authority of the ‘victim’. It is argued that populist impulses dominate, driving a tendency to use discourses of emotional authenticity and offence to legitimise demands for a plebiscitary response to popular of ‘victim’ preference and to close down controversy and debate, with the principal objective marketing the newspaper as an influential community champion

Angiostatin generating capacity and anti-tumour effects of D-penicillamine and plasminogen activators

BACKGROUND: Upregulation of endogenous angiostatin levels may constitute a novel anti-angiogenic, and therefore anti-tumor therapy. In vitro, angiostatin generation is a two-step process, starting with the conversion of plasminogen to plasmin by plasminogen activators (PAs). Next, plasmin excises angiostatin from other plasmin molecules, a process requiring a donor of a free sulfhydryl group. In previous studies, it has been demonstrated that administration of PA in combination with the free sulfhydryl donor (FSD) agents captopril or N-acetyl cysteine, resulted in angiostatin generation, and anti-angiogenic and anti-tumour activity in murine models. METHODS: In this study we have investigated the angiostatin generating capacities of several FSDs. D-penicillamine proved to be most efficient in supporting the conversion of plasminogen to angiostatin in vitro. Next, from the optimal concentrations of tPA and D-penicillamine in vitro, equivalent dosages were administered to healthy Balb/c mice to explore upregulation of circulating angiostatin levels. Finally, anti-tumor effects of treatment with tPA and D-penicillamine were determined in a human melanoma xenograft model. RESULTS: Surprisingly, we found that despite the superior angiostatin generating capacity of D-penicillamine in vitro, both in vivo angiostatin generation and anti-tumour effects of tPA/D-penicillamine treatment were impaired compared to our previous studies with tPA and captopril. CONCLUSION: Our results indicate that selecting the most appropriate free sulfhydryl donor for anti-angiogenic therapy in a (pre)clinical setting should be performed by in vivo rather than by in vitro studies. We conclude that D-penicillamine is not suitable for this type of therapy

Compressed collagen and decellularized tissue: novel components in a pipeline approach for the study of cancer metastasis

Metastasis is a complex process which is difficult to study and model. Experimental ingenuity is therefore essential when seeking to elucidate the biological mechanisms involved. Typically, in vitro models of metastasis have been overly simplistic, lacking the characteristic elements of the tumour microenvironment, whereas in vivo models are expensive, requiring specialist resources. Here we propose a pipeline approach for the study of cell migration and colonization, two critical steps in the metastatic cascade.We used a range of extracellular matrix derived contexts to facilitate a progressive approach to the observation and quantification of cell behaviour in 2D, 3D and at border zones between dimensions. At the simplest level, cells were set onto collagen-coated plastic or encapsulated within a collagen matrix. To enhance this, a collagen compression technique provided a stiffened, denser substrate which could be used as a 2D surface or to encapsulate cells. Decellularized tissue from the chorioallantoic membrane of the developing chicken embryo was used to provide a more structured, biologically relevant extracellular matrix-based context in which cell behaviour could then be compared with its in vivo counterpart.Cell behaviour could be observed and quantified within each context using standard laboratory techniques of microscopy and immunostaining, affording the opportunity for comparison and contrast of behaviour across the whole range of contexts. In particular, the temporal constraints of the in vivo CAM were removed when cells were cultured on the decellularized CAM, allowing for much longer-term cell colonization and cell-cell interaction.Together the assays within this pipeline provide the opportunity for the study of cell behaviour in a replicable way across multiple environments. The assays can be set up and analysed using easily available resources and standard laboratory equipment. We believe this offers the potential for the detailed study of cell migration and colonization of tissue, essential steps in the metastatic cascade. Also, we propose that the pipeline could be used in the wider arena of cell culture in general with the increasingly more complex contexts allowing cell behaviours and interactions to be explored in a stepwise fashion in an integrated way

Relative contribution of various chronic diseases and multi-morbidity to potential disability among Dutch elderly

BACKGROUND: The amount of time spent living with disease greatly influences elderly people’s wellbeing, disability and healthcare costs, but differs by disease, age and sex. METHODS: We assessed how various single and combined diseases differentially affect life years spent living with disease in Dutch elderly men and women (65+) over their remaining life course. Multistate life table calculations were applied to age and sex-specific disease prevalence, incidence and death rates for the Netherlands in 2007. We distinguished congestive heart failure, coronary heart disease (CHD), breast and prostate cancer, colon cancer, lung cancer, diabetes, COPD, stroke, dementia and osteoarthritis. RESULTS: Across ages 65, 70, 75, 80 and 85, CHD caused the most time spent living with disease for Dutch men (from 7.6 years at age 65 to 3.7 years at age 85) and osteoarthritis for Dutch women (from 11.7 years at age 65 to 4. 8 years at age 85). Of the various co-occurrences of disease, the combination of diabetes and osteoarthritis led to the most time spent living with disease, for both men (from 11.2 years at age 65 to 4.9 -years at age 85) and women (from 14.2 years at age 65 to 6.0 years at age 85). CONCLUSIONS: Specific single and multi-morbid diseases affect men and women differently at different phases in the life course in terms of the time spent living with disease, and consequently, their potential disability. Timely sex and age-specific interventions targeting prevention of the single and combined diseases identified could reduce healthcare costs and increase wellbeing in elderly people