874 research outputs found
Properties of pedestrians walking in line: Stepping behavior
In human crowds, interactions among individuals give rise to a variety of
self-organized collective motions that help the group to effectively solve the
problem of coordination. However, it is still not known exactly how humans
adjust their behavior locally, nor what are the direct consequences on the
emergent organization. One of the underlying mechanisms of adjusting individual
motions is the stepping dynamics. In this paper, we present first quantitative
analysis on the stepping behavior in a one-dimensional pedestrian flow studied
under controlled laboratory conditions. We find that the step length is
proportional to the velocity of the pedestrian, and is directly related to the
space available in front of him, while the variations of the step duration are
much smaller. This is in contrast with locomotion studies performed on isolated
pedestrians and shows that the local density has a direct influence on the
stepping characteristics. Furthermore, we study the phenomena of
synchronization -walking in lockstep- and show its dependence on flow
densities. We show that the synchronization of steps is particularly important
at high densities, which has direct impact on the studies of optimizing
pedestrians flow in congested situations. However, small synchronization and
antisynchronization effects are found also at very low densities, for which no
steric constraints exist between successive pedestrians, showing the natural
tendency to synchronize according to perceived visual signals.Comment: 8 pages, 5 figure
TSC22 in mammary gland development and breast cancer
Mammary gland involution is characterised by a high degree of apoptosis. By identifying genes that are upregulated at this developmental stage, we aimed to discover key factors that are involved in the induction of mammary epithelial cell death and therefore present potential tumour suppressors for breast cancer. Among 96 genes recently identified as specifically upregulated early during involution were the transforming growth factor beta (TGFβ)-stimulated clone 22 homologue (TSC-22/TGFβ1-induced transcript 4) and TGFβ3 [1]. TGFβ3 has recently been shown to be necessary for induction of apoptosis during mammary gland involution, while TSC-22 overexpression can lead to cell death. We have therefore tested whether TSC-22 mRNA expression can be induced by TGFβ3 and whether it is involved in or necessary for TGFβ-induced apoptosis. We further show that TSC-22 can enhance TGFβ3-induced Smad response and epithelial cell death. In addition, overexpression of TSC-22 alone can induce a Smad response and apoptosis in mammary epithelial cell cultures, which is independent of p53. Further, we have performed tests to study the necessity for Smad proteins during TSC-22-induced apoptosis, and to establish the intracellular localisation of TSC-22. A pilot study on a small cohort of archival breast cancer cases, representing all stages of malignant progression, shows that TSC-22 protein was reduced or undetectable in 60% of breast carcinomas when compared with adjacent normal breast tissue, suggesting that TSC-22 could indeed be a potential novel tumour suppressor gene. We shall present data showing that methylation of the TSC-22 promoter is not involved in the reduction of TSC-22 protein in breast cancer
RIPK1-mediated immunogenic cell death promotes anti-tumour immunity against soft-tissue sarcoma.
Drugs that mobilise the immune system against cancer are dramatically improving care for many people. Dying cancer cells play an active role in inducing anti-tumour immunity but not every form of death can elicit an immune response. Moreover, resistance to apoptosis is a major problem in cancer treatment and disease control. While the term "immunogenic cell death" is not fully defined, activation of receptor-interacting serine/threonine-protein kinase 1 (RIPK1) can induce a type of death that mobilises the immune system against cancer. However, no clinical treatment protocols have yet been established that would harness the immunogenic potential of RIPK1. Here, we report the first pre-clinical application of an in vivo treatment protocol for soft-tissue sarcoma that directly engages RIPK1-mediated immunogenic cell death. We find that RIPK1-mediated cell death significantly improves local disease control, increases activation of CD8+ T cells as well as NK cells, and enhances the survival benefit of immune checkpoint blockade. Our findings warrant a clinical trial to assess the survival benefit of RIPK1-induced cell death in patients with advanced disease at limb extremities
Lab Retriever: a software tool for calculating likelihood ratios incorporating a probability of drop-out for forensic DNA profiles
BACKGROUND: Technological advances have enabled the analysis of very small amounts of DNA in forensic cases. However, the DNA profiles from such evidence are frequently incomplete and can contain contributions from multiple individuals. The complexity of such samples confounds the assessment of the statistical weight of such evidence. One approach to account for this uncertainty is to use a likelihood ratio framework to compare the probability of the evidence profile under different scenarios. While researchers favor the likelihood ratio framework, few open-source software solutions with a graphical user interface implementing these calculations are available for practicing forensic scientists. RESULTS: To address this need, we developed Lab Retriever, an open-source, freely available program that forensic scientists can use to calculate likelihood ratios for complex DNA profiles. Lab Retriever adds a graphical user interface, written primarily in JavaScript, on top of a C++ implementation of the previously published R code of Balding. We redesigned parts of the original Balding algorithm to improve computational speed. In addition to incorporating a probability of allelic drop-out and other critical parameters, Lab Retriever computes likelihood ratios for hypotheses that can include up to four unknown contributors to a mixed sample. These computations are completed nearly instantaneously on a modern PC or Mac computer. CONCLUSIONS: Lab Retriever provides a practical software solution to forensic scientists who wish to assess the statistical weight of evidence for complex DNA profiles. Executable versions of the program are freely available for Mac OSX and Windows operating systems. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0740-8) contains supplementary material, which is available to authorized users
Mechanical Tension Increases CCN2/CTGF Expression and Proliferation in Gingival Fibroblasts via a TGFβ-Dependent Mechanism
Unlike skin, oral gingival do not scar in response to tissue injury. Fibroblasts,
the cell type responsible for connective tissue repair and scarring, are exposed
to mechanical tension during normal and pathological conditions including wound
healing and fibrogenesis. Understanding how human gingival fibroblasts respond
to mechanical tension is likely to yield valuable insights not only into
gingival function but also into the molecular basis of scarless repair.
CCN2/connective tissue growth factor is potently induced in fibroblasts during
tissue repair and fibrogenesis. We subjected gingival fibroblasts to cyclical
strain (up to 72 hours) using the Flexercell system and showed that CCN2 mRNA
and protein was induced by strain. Strain caused the rapid activation of latent
TGFβ, in a fashion that was reduced by blebbistatin and FAK/src inhibition,
and the induction of endothelin (ET-1) mRNA and protein expression. Strain did
not cause induction of α-smooth muscle actin or collagen type I mRNAs
(proteins promoting scarring); but induced a cohort of pro-proliferative mRNAs
and cell proliferation. Compared to dermal fibroblasts, gingival fibroblasts
showed reduced ability to respond to TGFβ by inducing fibrogenic mRNAs;
addition of ET-1 rescued this phenotype. Pharmacological inhibition of the
TGFβ type I (ALK5) receptor, the endothelin A/B receptors and FAK/src
significantly reduced the induction of CCN2 and pro-proliferative mRNAs and cell
proliferation. Controlling TGFβ, ET-1 and FAK/src activity may be useful in
controlling responses to mechanical strain in the gingiva and may be of value in
controlling fibroproliferative conditions such as gingival hyperplasia;
controlling ET-1 may be of benefit in controlling scarring in response to injury
in the skin
Omnichannel Value Chain: Mapping Digital Technologies for Channel Integration Activities
In order to provide a seamless customer experience, researchers and practitioners have proposed creation of an omnichannel retailing environment by integrating online and offline channels. Channel integration necessitates use of digital technologies and there are myriads of technological solutions available. However, retailers are struggling with selection and implementation of suitable technologies to add value through channel integration. Despite the strong practical need, this issue has not been effectively addressed in the academic literature. This paper presents an omnichannel value chain underpinned by Porter’s value chain model. We identify ten channel integration activities for value creation by carrying out a synthesis of current research on omnichannel retailing. Enabling digital technologies are then mapped to these activities using technology implementation examples and provide a guideline for retailers to select appropriate technologies for the identified value creation activities
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