Initial results of in vivo non-invasive cancer imaging in the human breast using near-infrared photoacoustics

Near-infrared photoacoustic images of regions-of-interest in 4 of the 5 cases of patients with symptomatic breasts reveal higher intensity regions which we attribute to vascular distribution associated with cancer. Of the 2 cases presented here, one is especially significant where benign indicators dominate in conventional radiological images, while photoacoustic images reveal vascular features suggestive of malignancy, which is corroborated by histopathology. The results show that photoacoustic imaging may have potential in visualizing certain breast cancers based on intrinsic optical absorption contrast. A future role for the approach could be in supplementing conventional breast imaging to assist detection and/or diagnosis.\ud \u

V_H replacement in rearranged immunoglobulin genes

Examples suggesting that all or part of the V<sub>H</sub> segment of a rearranged V<sub>H</sub>DJ<sub>H</sub> may be replaced by all or part of another V<sub>H</sub> have been appearing since the 1980s. Evidence has been presented of two rather different types of replacement. One of these has gained acceptance and has now been clearly demonstrated to occur. The other, proposed more recently, has not yet gained general acceptance because the same effect can be produced by polymerase chain reaction artefact. We review both types of replacement including a critical examination of evidence for the latter. The first type involves RAG proteins and recombination signal sequences (RSS) and occurs in immature B cells. The second was also thought to be brought about by RAG proteins and RSS. However, it has been reported in hypermutating cells which are not thought to express RAG proteins but in which activation-induced cytidine deaminase (AID) has recently been shown to initiate homologous recombination. Re-examination of the published sequences reveals AID target sites in V<sub>H</sub>-V<sub>H</sub> junction regions and examples that resemble gene conversion

Full probabilistic design of a submerged floating tunnel and format for partial safety factors

A submerged floating tunnel (SFT) can be a promising solution for crossing a deep or wide waterway. This innovative concept however lacks research into its probabilistic design. In this research, the reliability of the tether-stabilized SFT is assessed. A first-order reliability method (FORM) and a Monte Carlo simulation (MCS) are performed for the limit state functions of the most important failure mechanisms. Stochastic variables are chosen so that a target reliability index of 3.8 for a reference period of 50 years is met. The calculated factors from the full probabilistic design are compared with the general recommended partial factors for strength and resistance from Eurocode EN1990. For the strength mechanisms, the calculated factors are smaller than the factors from Eurocode. However, for the equilibrium mechanism, the calculated factor for the unfavorable loading is larger than the factor from Eurocode and should be increased by 10% in order to design a safe enough SFT

Eye–hand coordination during manual object transport with the affected and less affected hand in adolescents with hemiparetic cerebral palsy

In the present study we investigated eye–hand coordination in adolescents with hemiparetic cerebral palsy (CP) and neurologically healthy controls. Using an object prehension and transport task, we addressed two hypotheses, motivated by the question whether early brain damage and the ensuing limitations of motor activity lead to general and/or effector-specific effects in visuomotor control of manual actions. We hypothesized that individuals with hemiparetic CP would more closely visually monitor actions with their affected hand, compared to both their less affected hand and to control participants without a sensorimotor impairment. A second, more speculative hypothesis was that, in relation to previously established deficits in prospective action control in individuals with hemiparetic CP, gaze patterns might be less anticipatory in general, also during actions performed with the less affected hand. Analysis of the gaze and hand movement data revealed the increased visual monitoring of participants with CP when using their affected hand at the beginning as well as during object transport. In contrast, no general deficit in anticipatory gaze control in the participants with hemiparetic CP could be observed. Collectively, these findings are the first to directly show that individuals with hemiparetic CP adapt eye–hand coordination to the specific constraints of the moving limb, presumably to compensate for sensorimotor deficits

Mining for viral fragments in methylation enriched sequencing data

Most next generation sequencing experiments generate more data than is required for the experimental set up. For example, methyl-CpG binding domain (MBD) affinity purification based sequencing is often used for DNA-methylation profiling, but up to 30% of the sequenced fragments cannot be mapped uniquely to the reference genome. Here we present and evaluate a methodology for the identification of viruses in these otherwise unused paired-end MBD-seq data. Viral detection is accomplished by mapping non-reference alignable reads to a comprehensive set of viral genomes. As viruses play an important role in epigenetics and cancer development, 92 (pre)malignant and benign samples, originating from two different collections of cervical samples and related cell lines, were used in this study. These samples include primary carcinomas (n=22), low- & high-grade cervical intrapeithelial neoplasia (CIN1 & CIN2/3 - n=2/n=30) and normal tissue (n=20), as well as control samples (n=17). Viruses that were detected include phages, adenoviruses, herpesviridae and HPV. HPV, which causes virtually all cervical cancers, was identified in 95% of the carcinomas, 100% of the CIN2/3 samples, both CIN1 samples and in 55% of the normal samples. Comparing the amount of mapped fragments on HPV for each HPV-infected sample yielded a significant difference between normal samples and carcinomas or CIN2/3 samples (adjusted p-values resp. < 10^-5, < 10^-5), reflecting different viral loads and/or methylation degrees in non-normal samples. Fragments originating from different HPV types could be distinguished and were independently validated by PCR-based assays with a specificity of 98% and a sensitivitity of 66%. In conclusion, although limited by the a priori knowledge of viral reference genome sequences, the proposed methodology can provide a first but substantial insight into the presence, concentration and types of methylated viral sequences in MBD-seq data without additional costs

Actor roles in transition: Insights from sociological perspectives

AbstractTo date, the field of transition research lacks a suitable vocabulary to analyse the (changing) interactions and relations of actors as part of a sustainability transition. This article addresses this knowledge gap by exploring the potential of the concept of ‘roles’ from social interaction research. The role concept is operationalized for transition research to allow the analysis of (changing) roles and relations between actor roles as indicative of changes in the social fabric and shared values, norms and beliefs. It also allows considering the use of roles as a transition governance intervention. This includes creating new roles, breaking down or altering existing ones and explicitly negotiating or purposefully assigning roles, as well as the flexible use of roles as resources

How effortful is cognitive control? Insights from a novel method measuring single-trial evoked beta-adrenergic cardiac reactivity

The ability to adjust attentional focus to varying levels of task demands depends on the adaptive recruitment of cognitive control processes. The present study investigated for the first time whether the mobilization of cognitive control during response-conflict trials in a flanker task is associated with effort-related sympathetic activity as measured by changes in the RZinterval at a single-trial level, thus providing an alternative to the pre-ejection period (PEP) which can only be reliably measured in ensemble-averaged data. We predicted that response conflict leads to a physiological orienting response (i.e. heart rate slowing) and increases in effort as reflected by changes in myocardial beta-adrenergic activity (i.e. decreased RZ interval). Our results indeed showed that response conflict led to cardiac deceleration and decreased RZ interval. However, the temporal overlap of the observed heart rate and RZ interval changes suggests that the effect on the latter reflects a change in cardiac pre-load (Frank-Starling mechanism). Our study was thus unable to provide evidence for the expected link between cognitive control and cardiovascular effort. However, it demonstrated that our single-trial analysis enables the assessment of transient changes in cardiac sympathetic activity, thus providing a promising tool for future studies that aim to investigate effort at a single-trial level