β-Diketonate versus β-Ketoiminate: The Importance of a Ferrocenyl Moiety in Improving the Anticancer Potency

Herein we present a library of fully characterized β-diketonate and β-ketoiminate compounds that are functionalized with a ferrocenyl moiety. Their cytotoxic potential has been determined by screening against human breast adenocarcinomas (MCF-7 and MDA-MB-231), human colorectal carcinoma p53 wild type (HCT116 p53^+/+) and normal human prostate (PNT2) cell lines. The ferrocenyl β-diketonate compounds are more than 18 times more cytotoxic than the ferrocenyl β-ketoiminate analogues. Against MCF-7, compounds functionalized at the meta position are up to nine times more cytotoxic than when functionalized at the para position. The ferrocenyl β-diketonate compounds have increased selectivity towards MCF-7 and MDA-MB-231, with several complexes having selectivity index (SI) values that are more than nine times (MCF-7) and more than six times (MDA-MB-231) that of carboplatin. The stability of these compounds in dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) has been assessed by NMR spectroscopy and mass spectrometry studies, and the compounds show no oxidation of the iron center from Fe^II to Fe^III. Cytotoxicity screening was performed in both DMSO and DMF, with no significant differences observedin their potency.     

A toy or a friend? Children's anthropomorphic beliefs about robots and how these relate to second-language word learning

This study investigates the degree to which children anthropomorphize a robot tutor and whether this anthropomorphism relates to their vocabulary learning in a second-language (L2) tutoring intervention. With this aim, an anthropomorphism questionnaire was administered to 5-year-old children (N = 104) twice: prior to and following a seven-session L2 vocabulary training with a humanoid robot. On average, children tended to anthropomorphize the robot prior to and after the lessons to a similar degree, but many children changed their attributed anthropomorphic features. Boys anthropomorphized the robot less after the lessons than girls. Moreover, there was a weak but significant positive correlation between anthropomorphism as measured before the lessons and scores on a word-knowledge post-test administered the day after the last lesson. There was also a weak but significant positive correlation between the change in anthropomorphism over time and scores on a word-knowledge post-test administered approximately 2 weeks after the last lesson. Our results underscore the need to manage children's expectations in robot-assisted education. Also, future research could explore adaptations to individual children's expectations in child-robot interactions.     

Mining sequences with exceptional transition behaviour of varying order using quality measures based on information-theoretic scoring functions

Data Mining and Knowledge Discovery - Discrete Markov chains are frequently used to analyse transition behaviour in sequential data. Here, the transition probabilities can be estimated using...     

Intake of ruminant versus industrial trans fatty acids and risk of coronary heart disease – what is the evidence?

Several studies have reported a positive association between intake of trans fatty acids and risk of heart disease. It has been suggested that trans fatty acids from ruminant sources are less detrimental than trans fatty acids from industrial sources. Legislation or advice on limiting trans fatty acids has, in some instances, been restricted to trans fatty acids from industrial sources. However, comparisons of ruminant and industrial trans fatty acids have been based on few studies using relative intake data (e.g. quintiles of intakes). Therefore, we have reviewed data describing the associations between absolute intake (g eaten per day) of ruminant and industrial trans fatty acids and risk of coronary heart disease, and examined the associations graphically. Where direct comparison is possible, there are no differences in risk of coronary heart disease between total, ruminant and industrial trans fatty acids for intakes up to 2.5 g/d. At higher intakes (more than 3 g/d) total and industrial trans fatty acids are associated with an increased risk of coronary heart disease but there is insufficient data available on ruminant trans fatty acids at this level of intake. The scarce data do not support discrimination between ruminant and industrial trans fatty acids in dietary recommendations or legislation.     

Substructure-based virtual screening for adenosine A2A receptor ligands

A virtual ligand-based screening approach was designed and evaluated for the discovery of new A(2A) adenosine receptor (AR) ligands. For comparison and evaluation, the procedures from a recently published virtual screening study that used the A(2A) AR X-ray crystal structure for the target-based discovery of new A(2A) ligands were largely followed. Several screening models were constructed by deriving the distinguishing structural features from selected sets of A(2A) AR antagonists, so-called frequent substructure mining. The best model in statistical terms was subsequently applied to large-scale virtual screens of a commercial vendor library. This resulted in the selection of 36 candidates for acquisition and testing. Of the selected candidates, eight compounds significantly inhibited radioligand binding at A(2A) AR (>30%) at 10 μM, corresponding to a "hit rate" of 22%. This hit rate is quite similar to that of the referenced target-based virtual screening study, while both approaches yield new, non-overlapping sets of ligands.     

Placental Complement Activation in Fetal and Neonatal Alloimmune Thrombocytopenia: An Observational Study

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also bind to the placenta, causing placental damage. This study aims to explore signs of antibody-mediated placental damage in FNAIT. We performed a retrospective study that included pregnant women, their newborns, and placentas. It comprised 23 FNAIT cases, of which nine were newly diagnosed (14 samples) and 14 were antenatally treated with intravenous immune globulins (IVIg) (21 samples), and 20 controls, of which 10 had anti-HLA-class I antibodies. Clinical information was collected from medical records. Placental samples were stained for complement activation markers (C1q, C4d, SC5b-9, and mannose-binding lectin) using immunohistochemistry. Histopathology was examined according to the Amsterdam criteria. A higher degree of C4d deposition was present in the newly diagnosed FNAIT cases (10/14 samples), as compared to the IVIg-treated FNAIT cases (2/21 samples, p = 0.002) and anti-HLA-negative controls (3/20 samples, p = 0.006). A histopathological examination showed delayed maturation in four (44%) placentas in the newly diagnosed FNAIT cases, five (36%) in the IVIg-treated FNAIT cases, and one in the controls (NS). C4d deposition at the syncytiotrophoblast was present in combination with low-grade villitis of unknown etiology in three newly diagnosed FNAIT cases that were born SGA. We conclude that a higher degree of classical pathway-induced complement activation is present in placentas from pregnancies with untreated FNAIT. This may affect placental function and fetal growth.     

Understanding the Potential In Vitro Modes of Action of Bis(β-diketonato) Oxovanadium(IV) Complexes

To understand the potential in vitro modes of action of bis(β-diketonato) oxovanadium(IV) complexes, nine compounds of varying functionality have been screened using a range of biological techniques. The antiproliferative activity against a range of cancerous and normal cell lines has been determined, and show these complexes are particularly sensitive against the lung carcinoma cell line, A549. Annexin V (apoptosis) and Caspase-3/7 assays were studied to confirm these complexes induce programmed cell death. While gel electrophoresis was used to determine DNA cleavage activity and production of reactive oxygen species (ROS), the Comet assay was used to determine induced genomic DNA damage. Additionally, Förster resonance energy transfer (FRET)-based DNA melting and fluorescent intercalation displacement assays have been used to determine the interaction of the complexes with double strand (DS) DNA and to establish preferential DNA base-pair binding (AT versus GC).     

The influence of personality on user satisfaction: multi-tenant offices

Many different multi-tenant offices have arisen over the last decades, as building owners address the changing nature of the workplace – a need for users to share facilities. However, the existing literature on multi-tenant buildings from the point of view of user satisfaction is scarce, limiting input for user-centred design. This study analyses the influence of personality on user satisfaction with multi-tenant office characteristics. Data were collected through a questionnaire distributed among users of 17 different multi-tenant offices (business centres, incubators serviced offices and co-working places), which yielded 190 respondents. To determine the effects of personal characteristics, a multiple regression model was performed per office variable category. Results showed that users who are more extraverted, open to new experiences and more agreeable were overall more satisfied with the multi-tenant office characteristics. However, the effects of demographics and work-related characteristics were much larger. Men, older users and users working in an open and flexible work environment were overall more satisfied with the office characteristics. Owners, developers and managers can use these results for developing user-centred designs, optimizing the level of satisfaction in their offices.     

Analysing user preferences for co-working space characteristics

ABSTRACT

Over the past decades, the use of mobile technology has increased and the attitude towards work has changed, making it possible to work anywhere at any time. However, workers still seek work environments that stimulate networking and collaboration possibilities. This has led to the growing popularity of co-working spaces. However, little is known about the specific preferences of co-working space users. The aim of this research is to analyse user preferences for co-working space characteristics. Stated choice data were collected by means of a questionnaire which was completed by 219 respondents of 25 co-working spaces in the Netherlands. A mixed-multinomial logit model was used to analyse the user preferences. Results show that the main motivations for co-workers to work in a co-working space were that they were looking for a workplace outside their home that allows them to work in an inspiring work environment where the accommodation is affordable. Accessibility and atmosphere/interior are the most important characteristics when choosing a specific co-working space. These results provide owners or managers of co-working spaces with clear insights about how to cope with co-worker preferences by offering co-working spaces with good accessibility by car and public transport, a semi-open layout and a homelike interior.