2,260 research outputs found
Field investigation of deformation characteristics and stress mobilisation of a soil slope
Stress mobilisation and deformation of a slope are important for engineers to carry out reliable design of retaining systems. However, most case histories reported mainly on the response of pore-water pressure (PWP), whereas knowledge about the stress-deformation characteristics of slope is limited. In this study, a saprolitic soil slope was instrumented to monitor not only the responses of PWP but also horizontal stress and horizontal displacement. To assist in the interpretation of field data, a series of laboratory tests was conducted to characterise the volume change behaviour of soil taken from the site, under the effects of both net stress and suction. During a rainstorm event when positive PWP built up, a remarkably large displacement of 20 mm was recorded between 5.5 and 6 m depths, and the top 5 m of the slope exhibited translational down-slope movement. This caused an increase in effective horizontal stress by 350%, which reached a peak value close to 40% of an effective passive stress. During the subsequent dry season when suction was recovered, an up-slope rebound of 10 mm was recorded. Comparison of field and laboratory data reveals that the rebound was attributed to suction-induced soil shrinkage. This rebound led to a decrease in the effective horizontal stress previously built up during the storm event
Targeted knock-down of miR21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines
We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2
Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis
Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al
Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs
Non-conding RNAs play a key role in the post-transcriptional regulation of
mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact
with their target RNAs through protein-mediated, sequence-specific binding,
giving rise to extended and highly heterogeneous miRNA-RNA interaction
networks. Within such networks, competition to bind miRNAs can generate an
effective positive coupling between their targets. Competing endogenous RNAs
(ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk.
Albeit potentially weak, ceRNA interactions can occur both dynamically,
affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA
networks as a whole can be implicated in the composition of the cell's
proteome. Many features of ceRNA interactions, including the conditions under
which they become significant, can be unraveled by mathematical and in silico
models. We review the understanding of the ceRNA effect obtained within such
frameworks, focusing on the methods employed to quantify it, its role in the
processing of gene expression noise, and how network topology can determine its
reach.Comment: review article, 29 pages, 7 figure
Centrifuge modelling of the effects of root geometry on transpiration-induced suction and stability of vegetated slopes
Shallow landslides (i.e., 1 - 2 m depth) on both man-made and natural slopes are of major concern worldwide that has led to huge amount of socio-economical losses. The use of vegetation has been considered as an environmentally friendly means of stabilising slopes. Existing studies have focused on the use of plant roots with different geometries to mechanically stabilise soil slopes, but there are little data available on the contribution of transpiration-induced suction to slope stability. This study was designed to quantify both the hydrological and mechanical effects of root geometry on the stability of shallow slopes. Centrifuge tests were conducted to measure soil suction in slope models supported by newly-developed artificial roots. These artificial roots exhibit three different representative geometries (i.e., tap, heart and plate) and could simulate the effects of transpiration. The measured suction was then back-analysed through a series of finite element seepage-stability analyses to determine the factor of safety (FOS). It is revealed that after a rainfall event with a return period of 1000 years, the slope supported by heart-shaped roots retained the highest suction of 3 kPa within the root depth and thus this type of root provided the greatest stabilisation effects. The FOS of the slope supported by the heart-shaped roots, through both mechanical reinforcement and transpiration-induced suction, is 16% and 28% higher than that supported by the tap- and plate-shaped roots, respectively
The mu - e Conversion in Nuclei, mu --> e gamma, mu --> 3e Decays and TeV Scale See-Saw Scenarios of Neutrino Mass Generation
We perform a detailed analysis of lepton flavour violation (LFV) within
minimal see-saw type extensions of the Standard Model (SM), which give a viable
mechanism of neutrino mass generation and provide new particle content at the
electroweak scale. We focus, mainly, on predictions and constraints set on each
scenario from mu --> e gamma, mu --> 3e and mu - e conversion in the nuclei. In
this class of models, the flavour structure of the Yukawa couplings between the
additional scalar and fermion representations and the SM leptons is highly
constrained by neutrino oscillation measurements. In particular, we show that
in some regions of the parameters space of type I and type II see-saw models,
the Dirac and Majorana phases of the neutrino mixing matrix, the ordering and
hierarchy of the active neutrino mass spectrum as well as the value of the
reactor mixing angle theta_{13} may considerably affect the size of the LFV
observables. The interplay of the latter clearly allows to discriminate among
the different low energy see-saw possibilities.Comment: Expressions for the factors |C_{me}|^2 and |C_{mu3e}|^2 in the mu-e
conversion and mu-->3e decay rates, eqs. (36) and (49), respectively,
corrected; results in subsections 2.2 and 2.3 quantitatively changed,
qualitatively remain the same; figures 2, 3, 4 and 5 replace
PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK- and IRE1α-mediated unfolded protein response
Poly(ADP-ribose) polymerases (PARPs; also known as ADP-ribosyl transferase D proteins) modify acceptor proteins with ADP-ribose modifications of varying length (reviewed in refs 1, 2, 3). PARPs regulate key stress response pathways, including DNA damage repair and the cytoplasmic stress response. Here, we show that PARPs also regulate the unfolded protein response (UPR) of the endoplasmic reticulum (ER). Human PARP16 (also known as ARTD15) is a tail-anchored ER transmembrane protein required for activation of the functionally related ER stress sensors PERK and IRE1α during the UPR. The third identified ER stress sensor, ATF6, is not regulated by PARP16. As is the case for other PARPs that function during stress, the enzymatic activity of PARP16 is upregulated during ER stress when it ADP-ribosylates itself, PERK and IRE1α. ADP-ribosylation by PARP16 is sufficient for activating PERK and IRE1α in the absence of ER stress, and is required for PERK and IRE1α activation during the UPR. Modification of PERK and IRE1α by PARP16 increases their kinase activities and the endonuclease activity of IRE1α. Interestingly, the carboxy-terminal luminal tail of PARP16 is required for PARP16 function during ER stress, suggesting that it transduces stress signals to the cytoplasmic PARP catalytic domain.National Cancer Institute (U.S.) (Cancer Center Support Core Grant P30-CA14051)National Institutes of Health (U.S.) (Grant 5R01 GM087465-02)Kathy and Curt Marble Cancer Research FundJeptha H. and Emily V. Wade FundVirginia and D.K. Ludwig Fund for Cancer Researc
A survey of performance enhancement of transmission control protocol (TCP) in wireless ad hoc networks
This Article is provided by the Brunel Open Access Publishing Fund - Copyright @ 2011 Springer OpenTransmission control protocol (TCP), which provides reliable end-to-end data delivery, performs well in traditional wired network environments, while in wireless ad hoc networks, it does not perform well. Compared to wired networks, wireless ad hoc networks have some specific characteristics such as node mobility and a shared medium. Owing to these specific characteristics of wireless ad hoc networks, TCP faces particular problems with, for example, route failure, channel contention and high bit error rates. These factors are responsible for the performance degradation of TCP in wireless ad hoc networks. The research community has produced a wide range of proposals to improve the performance of TCP in wireless ad hoc networks. This article presents a survey of these proposals (approaches). A classification of TCP improvement proposals for wireless ad hoc networks is presented, which makes it easy to compare the proposals falling under the same category. Tables which summarize the approaches for quick overview are provided. Possible directions for further improvements in this area are suggested in the conclusions. The aim of the article is to enable the reader to quickly acquire an overview of the state of TCP in wireless ad hoc networks.This study is partly funded by Kohat University of Science & Technology (KUST),
Pakistan, and the Higher Education Commission, Pakistan
Prevalence of ocular and oculodermal melanocytosis in Spanish population with uveal melanoma
Producción CientíficaThe aim of this study was to determine the prevalence of ocular and oculodermal melanocytosis (ODM) among patients with uveal melanoma (UM) in a Spanish population.
METHODS:
Retrospective review of the medical records of patients with ODM among patients with UM.
RESULTS:
Ten (11 eyes) of 400 patients (2.7%) with UM associated had ODM. The mean age at diagnosis of UM among patients with ODM was 62 years. One patient had bilateral tumours. UM was diagnosed during a routine-examination in two cases. All tumours were medium (7/11) or large (4/11) in size, with a mean maximum base of 13 mm and height of 7 mm. No patient had extraocular extension or metastatic disease at diagnosis. Enucleation was done in five cases and I-125-brachytherapy in six. The mean follow-up was 43 months. One patient died because of metastasis 2 years after enucleation; one patient is currently on treatment of systemic metastasis 11 years after.
CONCLUSIONS:
ODM is more frequent in spanish population with UM than in American population. Despite the risk of UM in ODM, it is often diagnosed late when a conservative treatment is not indicated
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