400 research outputs found
Control of vehicle driving model by non-linear controller
A new drive control system which has an effect on controlling the vehicle slip during accelerating and braking is proposed in this paper. This drive control system uses a nonlinear controller designed by following the Lyapunov theorem. The controller is designed in order that it can work at both conditions that is the slippery and non-slippery road. The effectiveness of this control system is proved by a basic experiments
Spatial control of Cdc42 signalling by a GM130-RasGRF complex regulates polarity and tumorigenesis
The small GTPase Cdc42 is a key regulator of polarity, but little is known in mammals about its spatial regulation and the relevance of spatial Cdc42 pools for polarity. Here we report the identification of a GM130-RasGRF complex as a regulator of Cdc42 at the Golgi. Silencing GM130 results in RasGRF-dependent inhibition of the Golgi pool of Cdc42, but does not affect Cdc42 at the cell surface. Furthermore, active Cdc42 at the Golgi is important to sustain asymmetric front-rear Cdc42-GTP distribution in directionally migrating cells. Concurrent to Cdc42 inhibition, silencing GM130 also results in RasGRF-dependent Ras-ERK pathway activation. Moreover, depletion of GM130 is sufficient to induce E-cadherin downregulation, indicative of a loss in cell polarity and epithelial identity. Accordingly, GM130 expression is frequently lost in colorectal and breast cancer patients. These findings establish a previously unrecognized role for a GM130-RasGRF-Cdc42 connection in regulating polarity and tumorigenesis
Wnt signaling in triple negative breast cancer is associated with metastasis
Background
Triple Negative subset of (TN) Breast Cancers (BC), a close associate of the basal-like subtype (with limited discordance) is an aggressive form of the disease which convey unpredictable, and poor prognosis due to limited treatment options and lack of proven effective targeted therapies.
Methods
We conducted an expression study of 240 formalin-fixed, paraffin-embedded (FFPE) primary biopsies from two cohorts, including 130 TN tumors, to identify molecular mechanisms of TN disease.
Results
The annotation of differentially expressed genes in TN tumors contained an overrepresentation of canonical Wnt signaling components in our cohort and others. These observations were supported by upregulation of experimentally induced oncogenic Wnt/β-catenin genes in TN tumors, recapitulated using targets induced by Wnt3A. A functional blockade of Wnt/β-catenin pathway by either a pharmacological Wnt-antagonist, WntC59, sulidac sulfide, or β-catenin (functional read out of Wnt/β-catenin pathway) SiRNA mediated genetic manipulation demonstrated that a functional perturbation of the pathway is causal to the metastasis- associated phenotypes including fibronectin-directed migration, F-actin organization, and invasion in TNBC cells. A classifier, trained on microarray data from β-catenin transfected mammary cells, identified a disproportionate number of TNBC breast tumors as compared to other breast cancer subtypes in a meta-analysis of 11 studies and 1,878 breast cancer patients, including the two cohorts published here. Patients identified by the Wnt/β-catenin classifier had a greater risk of lung and brain, but not bone metastases.
Conclusion
These data implicate transcriptional Wnt signaling as a hallmark of TNBC disease associated with specific metastatic pathways
Searches for very high energy gamma rays from blazars with CANGAROO-III telescope in 2005-2009
We have searched for very high energy (VHE) gamma rays from four blazars
using the CANGAROO-III imaging atmospheric Cherenkov telescope. We report the
results of the observations of H 2356-309, PKS 2155-304, PKS 0537-441, and 3C
279, performed from 2005 to 2009, applying a new analysis to suppress the
effects of the position dependence of Cherenkov images in the field of view. No
significant VHE gamma ray emission was detected from any of the four blazars.
The GeV gamma-ray spectra of these objects were obtained by analyzing Fermi/LAT
archival data. Non-simultaneous wide range (radio to VHE gamma-ray bands)
spectral energy distributions (SEDs) including CANGAROO-III upper limits, GeV
gamma-ray spectra, and archival data are discussed using a one-zone synchrotron
self-Compton (SSC) model in combination with a external Compton (EC) radiation.
The HBLs (H 2356-309 and PKS 2155-304) can be explained by a simple SSC model,
and PKS 0537-441 and 3C 279 are well modeled by a combination of SSC and EC
model. We find a consistency with the blazar sequence in terms of strength of
magnetic field and component size.Comment: 11 pages, 8 figures, Accepted for publication in Astroparticle
Physic
Expression of Mcm2, geminin and Ki67 in normal oral mucosa, oral epithelial dysplasias and their corresponding squamous-cell carcinomas
Proteins necessary for the normal regulation of the cell cycle include minichromosome maintenance protein 2 (Mcm2) and geminin.
These are overexpressed in several premalignant and malignant tumours. The Mcm2/Ki67 ratio can be used to estimate the
population of cells that are in early G1 (licensed to proliferate), and the geminin/Ki67 ratio can determine the relative length of G1.
A high ratio indicates a short G1 and a high rate of cell proliferation. Mcm2 and geminin have been scarcely explored in oral epithelial
dysplasia (OED) and oral squamous-cell carcinoma (OSCC). The purpose of this study was to identify the expression pattern of
Mcm2, Ki67 and geminin in normal oral mucosa (NOM), OED and their subsequent OSCC, to determine if expression could help
predict the prognosis of OED. Paraffin sections of 41 OED cases that progressed to carcinoma, 40 OED without malignant
progression, 38 OSCC and 15 NOM were immunostained with antibodies against Mcm2, geminin and Ki67. Labelling indices (LIs)
increased progressively from NOM, OED and OSCC (Mcm2, Po0.001; geminin, Po0.001 and Ki67, Po0.001). In all the OED cases
(n ¼ 81) the levels of expression of Mcm2 (LI, 73.6), geminin (LI, 24.4) and Ki67 (LI, 44.5) were elevated indicating a constant cellcycle
re-entry. When the OED groups were compared, Mcm2 protein expression was higher in the OED with malignant progression
(P ¼ 0.04), likewise there was a significant increase in the Mcm2/Ki67 and geminin/Ki67 ratios (P ¼ 0.04 and 0.02 respectively). Mcm2
and geminin proteins seem to be novel biomarkers of growth and may be useful prognostic tools for OED
The Cherenkov Telescope Array Large Size Telescope
The two arrays of the Very High Energy gamma-ray observatory Cherenkov
Telescope Array (CTA) will include four Large Size Telescopes (LSTs) each with
a 23 m diameter dish and 28 m focal distance. These telescopes will enable CTA
to achieve a low-energy threshold of 20 GeV, which is critical for important
studies in astrophysics, astroparticle physics and cosmology. This work
presents the key specifications and performance of the current LST design in
the light of the CTA scientific objectives.Comment: 4 pages, 5 figures, In Proceedings of the 33rd International Cosmic
Ray Conference (ICRC2013), Rio de Janeiro (Brazil). All CTA contributions at
arXiv:1307.223
Detection of bridge emission above 50 GeV from the Crab pulsar with the MAGIC telescopes
The Crab pulsar is the only astronomical pulsed source detected at very high
energy (VHE, E>100GeV) gamma-rays. The emission mechanism of VHE pulsation is
not yet fully understood, although several theoretical models have been
proposed. In order to test the new models, we measured the light curve and the
spectra of the Crab pulsar with high precision by means of deep observations.
We analyzed 135 hours of selected MAGIC data taken between 2009 and 2013 in
stereoscopic mode. In order to discuss the spectral shape in connection with
lower energies, 4.6 years of {\it Fermi}-LAT data were also analyzed. The known
two pulses per period were detected with a significance of and
. In addition, significant emission was found between the two
pulses with . We discovered the bridge emission above 50 GeV
between the two main pulses. This emission can not be explained with the
existing theories. These data can be used for testing new theoretical models.Comment: 5 pages, 4 figure
First broadband characterization and redshift determination of the VHE blazar MAGIC J2001+439
We aim to characterize the broadband emission from 2FGL J2001.1+4352, which
has been associated with the unknown-redshift blazar MG4 J200112+4352. Based on
its gamma-ray spectral properties, it was identified as a potential very high
energy (VHE; E > 100 GeV) gamma-ray emitter. The source was observed with MAGIC
first in 2009 and later in 2010 within a multi-instrument observation campaign.
The MAGIC observations yielded 14.8 hours of good quality stereoscopic data.
The object was monitored at radio, optical and gamma-ray energies during the
years 2010 and 2011. The source, named MAGIC J2001+439, is detected for the
first time at VHE with MAGIC at a statistical significance of 6.3 {\sigma} (E >
70 GeV) during a 1.3-hour long observation on 2010 July 16. The
multi-instrument observations show variability in all energy bands with the
highest amplitude of variability in the X-ray and VHE bands. We also organized
deep imaging optical observations with the Nordic Optical Telescope in 2013 to
determine the source redshift. We determine for the first time the redshift of
this BL Lac object through the measurement of its host galaxy during low blazar
activity. Using the observational evidence that the luminosities of BL Lac host
galaxies are confined to a relatively narrow range, we obtain z = 0.18 +/-
0.04. Additionally, we use the Fermi-LAT and MAGIC gamma-ray spectra to provide
an independent redshift estimation, z = 0.17 +/- 0.10. Using the former (more
accurate) redshift value, we adequately describe the broadband emission with a
one-zone SSC model for different activity states and interpret the few-day
timescale variability as produced by changes in the high-energy component of
the electron energy distribution.Comment: 17 pages, 15 figures, Accepted for publication in A&
Measurement of the Crab Nebula spectrum over three decades in energy with the MAGIC telescopes
The MAGIC stereoscopic system collected 69 hours of Crab Nebula data between
October 2009 and April 2011. Analysis of this data sample using the latest
improvements in the MAGIC stereoscopic software provided an unprecedented
precision of spectral and night-by-night light curve determination at gamma
rays. We derived a differential spectrum with a single instrument from 50 GeV
up to almost 30 TeV with 5 bins per energy decade. At low energies, MAGIC
results, combined with Fermi-LAT data, show a flat and broad Inverse Compton
peak. The overall fit to the data between 1 GeV and 30 TeV is not well
described by a log-parabola function. We find that a modified log-parabola
function with an exponent of 2.5 instead of 2 provides a good description of
the data (). Using systematic uncertainties of red the MAGIC and
Fermi-LAT measurements we determine the position of the Inverse Compton peak to
be at (53 3stat + 31syst -13syst) GeV, which is the most precise
estimation up to date and is dominated by the systematic effects. There is no
hint of the integral flux variability on daily scales at energies above 300 GeV
when systematic uncertainties are included in the flux measurement. We consider
three state- of-the-art theoretical models to describe the overall spectral
energy distribution of the Crab Nebula. The constant B-field model cannot
satisfactorily reproduce the VHE spectral measurements presented in this work,
having particular difficulty reproducing the broadness of the observed IC peak.
Most probably this implies that the assumption of the homogeneity of the
magnetic field inside the nebula is incorrect. On the other hand, the
time-dependent 1D spectral model provides a good fit of the new VHE results
when considering a 80 {\mu}G magnetic field. However, it fails to match the
data when including the morphology of the nebula at lower wavelengths.Comment: accepted by JHEAp, 9 pages, 6 figure
- …