Modeling pedestrian evacuation movement in a swaying ship

With the advance in living standard, cruise travel has been rapidly expanding around the world in recent years. The transportation of passengers in water has also made a rapid development. It is expected that ships will be more and more widely used. Unfortunately, ship disasters occurred in these years caused serious losses. It raised the concern on effectiveness of passenger evacuation on ships. The present study thus focuses on pedestrian evacuation features on ships. On ships, passenger movements are affected by the periodical water motion and thus are quite different from the characteristic when walking on static horizontal floor. Taking into consideration of this special feature, an agent-based pedestrian model is formulized and the effect of ship swaying on pedestrian evacuation efficiency is investigated. Results indicated that the proposed model can be used to quantify the special evacuation process on ships.Comment: Traffic and Granular Flow'15, At Delft, the Netherland

W/Z Bremsstrahlung as the Dominant Annihilation Channel for Dark Matter, Revisited

We revisit the calculation of electroweak bremsstrahlung contributions to dark matter annihilation. Dark matter annihilation to leptons is necessarily accompanied by electroweak radiative corrections, in which a $W$ or $Z$ boson is also radiated. Significantly, while many dark matter models feature a helicity suppressed annihilation rate to fermions, bremsstrahlung process can remove this helicity suppression such that the branching ratios Br($\ell \nu W$), Br($\ell^+\ell^-Z$), and Br($\bar\nu \nu Z$) dominate over Br($\ell^+\ell^-$) and Br($\bar\nu \nu$). We find this is most significant in the limit where the dark matter mass is nearly degenerate with the mass of the boson which mediates the annihilation process. Electroweak bremsstrahlung has important phenomenological consequences both for the magnitude of the total dark matter annihilation cross section and for the character of the astrophysical signals for indirect detection. Given that the $W$ and $Z$ gauge bosons decay dominantly via hadronic channels, it is impossible to produce final state leptons without accompanying protons, antiprotons, and gamma rays.Comment: 8 pages, 6 figures; replaced to match published versio

Biomechanical coupling facilitates spinal neural tube closure in mouse embryos

Neural tube (NT) formation in the spinal region of the mammalian embryo involves a wave of “zippering” that passes down the elongating spinal axis, uniting the neural fold tips in the dorsal midline. Failure of this closure process leads to open spina bifida, a common cause of severe neurologic disability in humans. Here, we combined a tissue-level strain-mapping workflow with laser ablation of live-imaged mouse embryos to investigate the biomechanics of mammalian spinal closure. Ablation of the zippering point at the embryonic dorsal midline causes far-reaching, rapid separation of the elevating neural folds. Strain analysis revealed tissue expansion around the zippering point after ablation, but predominant tissue constriction in the caudal and ventral neural plate zone. This zone is biomechanically coupled to the zippering point by a supracellular F-actin network, which includes an actin cable running along the neural fold tips. Pharmacologic inhibition of F-actin or laser ablation of the cable causes neural fold separation. At the most advanced somite stages, when completion of spinal closure is imminent, the cable forms a continuous ring around the neuropore, and simultaneously, a new caudal-to-rostral zippering point arises. Laser ablation of this new closure initiation point causes neural fold separation, demonstrating its biomechanical activity. Failure of spinal closure in pre-spina bifida Zic2Ku mutant embryos is associated with altered tissue biomechanics, as indicated by greater neuropore widening after ablation. Thus, this study identifies biomechanical coupling of the entire region of active spinal neurulation in the mouse embryo as a prerequisite for successful NT closure

Direct-current-dependent shift of theta-burst-induced plasticity in the human motor cortex

Animal studies using polarising currents have shown that induction of synaptic long-term potentiation (LTP) and long-term depression (LTD) by bursts of patterned stimulation is affected by the membrane potential of the postsynaptic neurone. The aim of the present experiments was to test whether it is possible to observe similar phenomena in humans with the aim of improving present protocols of inducing synaptic plasticity for therapeutic purposes. We tested whether the LTP/LTD-like after effects of transcranial theta-burst stimulation (TBS) of human motor cortex, an analogue of patterned electrical stimulation in animals, were affected by simultaneous transcranial direct-current stimulation (tDCS), a non-invasive method of polarising cortical neurones in humans. Nine healthy volunteers were investigated in a single-blind, balanced cross-over study; continuous TBS (cTBS) was used to introduce LTD-like after effects, whereas intermittent TBS (iTBS) produced LTP-like effects. Each pattern was coupled with concurrent application of tDCS (<200 s, anodal, cathodal, sham). Cathodal tDCS increased the response to iTBS and abolished the effects of cTBS. Anodal tDCS changed the effects of cTBS towards facilitation, but had no impact on iTBS. Cortical motor thresholds and intracortical inhibitory/facilitatory networks were not altered by any of the stimulation protocols. We conclude that the after effects of TBS can be modulated by concurrent tDCS. We hypothesise that tDCS changes the membrane potential of the apical dendrites of cortical pyramidal neurones and that this changes the response to patterned synaptic input evoked by TBS. The data show that it may be possible to enhance LTP-like plasticity after TBS in the human cortex

Exposure to the tsunami disaster, PTSD symptoms and increased substance use – an Internet based survey of male and female residents of Switzerland

BACKGROUND: After the tsunami disaster in the Indian Ocean basin an Internet based self-screening test was made available in order to facilitate contact with mental health services. Although primarily designed for surviving Swiss tourists as well as relatives and acquaintances of the victims, the screening instrument was open to anyone who felt psychologically affected by this disaster. The aim of this study was to evaluate the influences between self-declared increased substance use in the aftermath of the tsunami disaster, trauma exposure and current PTSD symptoms. METHODS: One section of the screening covered addiction related behavior. We analyzed the relationship between increased substance use, the level of PTSD symptoms and trauma exposure using multivariable logistic regression with substance use as the dependent variable. Included in the study were only subjects who reported being residents of Switzerland and the analyses were stratified by gender in order to control for possible socio-cultural or gender differences in the use of psychotropic substances. RESULTS: In women PTSD symptoms and degree of exposure enlarged the odds of increased alcohol, pharmaceuticals and cannabis use significantly. In men the relationship was more specific: PTSD symptoms and degree of exposure only enlarged the odds of increased pharmaceutical consumption significantly. Increases in alcohol, cannabis and tobacco use were only significantly associated with the degree of PTSD symptoms. CONCLUSION: The tsunami was associated with increased substance use. This study not only replicates earlier findings but also suggests for a gender specificity of post-traumatic substance use increase

The N-terminal intrinsically disordered domain of mgm101p is localized to the mitochondrial nucleoid.

The mitochondrial genome maintenance gene, MGM101, is essential for yeasts that depend on mitochondrial DNA replication. Previously, in Saccharomyces cerevisiae, it has been found that the carboxy-terminal two-thirds of Mgm101p has a functional core. Furthermore, there is a high level of amino acid sequence conservation in this region from widely diverse species. By contrast, the amino-terminal region, that is also essential for function, does not have recognizable conservation. Using a bioinformatic approach we find that the functional core from yeast and a corresponding region of Mgm101p from the coral Acropora millepora have an ordered structure, while the N-terminal domains of sequences from yeast and coral are predicted to be disordered. To examine whether ordered and disordered domains of Mgm101p have specific or general functions we made chimeric proteins from yeast and coral by swapping the two regions. We find, by an in vivo assay in S.cerevisiae, that the ordered domain of A.millepora can functionally replace the yeast core region but the disordered domain of the coral protein cannot substitute for its yeast counterpart. Mgm101p is found in the mitochondrial nucleoid along with enzymes and proteins involved in mtDNA replication. By attaching green fluorescent protein to the N-terminal disordered domain of yeast Mgm101p we find that GFP is still directed to the mitochondrial nucleoid where full-length Mgm101p-GFP is targeted

Prognostic utility of HOXB13 : IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial

Background: A dichotomous index combining two gene expression assays, HOXB13:IL17BR (H:I) and molecular grade index (MGI), was developed to assess risk of recurrence in breast cancer patients. The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer. Methods: In a blinded retrospective analysis of 588 ER-positive tamoxifen-treated and untreated breast cancer patients from the randomized prospective Stockholm trial, H:I and MGI were measured using real-time RT-PCR. Association with patient outcome was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. A continuous risk index was developed using Cox modeling. Results: The dichotomous H:I+MGI was significantly associated with distant recurrence and breast cancer death. The &gt;50% of tamoxifen-treated patients categorized as low-risk had &lt;3% 10-year distant recurrence risk. A continuous risk model (Breast Cancer Index (BCI)) was developed with the tamoxifen-treated group and the prognostic performance tested in the untreated group was 53% of patients categorized as low-risk with an 8.3% 10-year distant recurrence risk. Conclusion: Retrospective analysis of this randomized, prospective trial cohort validated the prognostic utility of H:I+MGI and was used to develop and test a continuous risk model that enables prediction of distant recurrence risk at the patient level.Original Publication:Piiha-Lotta Jerevall, Xiai-Jun Ma, Hongying Li, Ranelle Salunga, Nicole C. Kesty, Mark G. Erlander, Dennis Sgroi, Birgitta Holmlund, Lambert Skoog, Tommy Fornander, Bo Nordenskjöld and Olle Stål, Prognostic utility of HOXB13:IL17BR and Molecular Grade Index in early-stage breast cancer patients from the Stockholm trial, 2011, British Journal of Cancer, (104), 11, 1762-1769.http://dx.doi.org/10.1038/bjc.2011.145Copyright: Nature Publishing Grouphttp://npg.nature.com

Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms. Methodology/Principal Findings: We have generated fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as confirmed by immunocytochemical analysis of cell specific markers. The three YG8R mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat stability, together with reduced expression of frataxin and reduced aconitase activity compared to control Y47R cells. Furthermore, YG8R cells also show increased sensitivity to oxidative stress and downregulation of Pgc-1α and antioxidant gene expression levels, especially Sod2. We also analysed various DNA mismatch repair (MMR) gene expression levels and found that YG8R cells displayed significant reduction in expression of several MMR genes, which may contribute to the GAA repeat stability. Conclusions/Significance: We describe the first fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be differentiated into neurons and glia. These novel FRDA mouse cell models, which exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources to further study FRDA molecular pathogenesis. They will also provide very useful tools for preclinical testing of frataxin-increasing compounds for FRDA drug therapy, for gene therapy, and as a source of cells for cell therapy testing in FRDA mice. © 2014 Sandi et al

Prognostic significance of immunohistochemically detected breast cancer node metastases in 218 patients

Axillary lymph node metastases detected by immunohistochemistry in standard node-negative patients with breast carcinomas (13 out of 129 infiltrating ductal carcinomas and 37 out of 89 infiltrating lobular carcinomas) do not have any prognostic significance in patients followed up for a long time (respectively 24 and 18 years). Moreover, their pejorative significance in the literature is debatable since the groups and events taken into account are heterogeneous

An Explicit Strategy Prevails When the Cerebellum Fails to Compute Movement Errors

In sensorimotor adaptation, explicit cognitive strategies are thought to be unnecessary because the motor system implicitly corrects performance throughout training. This seemingly automatic process involves computing an error between the planned movement and actual feedback of the movement. When explicitly provided with an effective strategy to overcome an experimentally induced visual perturbation, people are immediately successful and regain good task performance. However, as training continues, their accuracy gets worse over time. This counterintuitive result has been attributed to the independence of implicit motor processes and explicit cognitive strategies. The cerebellum has been hypothesized to be critical for the computation of the motor error signals that are necessary for implicit adaptation. We explored this hypothesis by testing patients with cerebellar degeneration on a motor learning task that puts the explicit and implicit systems in conflict. Given this, we predicted that the patients would be better than controls in maintaining an effective strategy assuming strategic and adaptive processes are functionally and neurally independent. Consistent with this prediction, the patients were easily able to implement an explicit cognitive strategy and showed minimal interference from undesirable motor adaptation throughout training. These results further reveal the critical role of the cerebellum in an implicit adaptive process based on movement errors and suggest an asymmetrical interaction of implicit and explicit processes