560 research outputs found
Guidelines for the design of haptic widgets
Haptic feedback has been shown to improve user performance in Graphical User Interface (GUI) targeting tasks in a number of studies. These studies have typically focused on interactions with individual targets, and it is unclear whether the performance increases reported will generalise to the more realistic situation where multiple targets are presented simultaneously. This paper addresses this issue in two ways. Firstly two empirical studies dealing with groups of haptically augmented widgets are presented. These reveal that haptic augmentations of complex widgets can reduce performance, although carefully designed feedback can result in performance improvements. The results of these studies are then used in conjunction with the previous literature to generate general design guidelines for the creation of haptic widgets
Strangeness production in proton-proton and proton-nucleus collisions
In these lectures we discuss the investigation of the strange meson
production in proton-proton () and in proton-nucleus () reactions
within an effective Lagrangian model. The kaon production proceeds mainly via
the excitations of (1650), (1710), and (1720) resonant
intermediate nucleonic states, in the collision of two initial state nucleons.
Therefore, the strangeness production is expected to provide information about
the resonances lying at higher excitation energies. For beam energies very
close to the kaon production threshold the hyperon-proton final state
interaction effects are quite important. Thus, these studies provide a check on
the models of hyperon-nucleon interactions. The in-medium production of kaons
show strong sensitivity to the self energies of the intermediate mesons.Comment: 16 pages, 9 figures, Talk presented in the workshop on Hadron
Physics, Puri, India, March 7-17,200
Coherent excitation transferring via dark state in light-harvesting process
We study the light absorption and energy transferring in a donor-acceptor
system with a bionic structure. In the optimal case with uniform couplings, it
is found that the quantum dynamics of this seemingly complicated system is
reduced as a three-level system of -type. With this observation, we
show that the dark state based electromagnetically-induced transparency (EIT)
effect could enhance the energy transfer efficiency, through a quantum
interference effect suppressing the excited population of the donors. We
estimate the optimal parameters of the system to achieve the maximum output
power. The splitting behavior of maximum power may be used to explain the
phenomenon that the photosynthesis systems mainly absorb two colors of light.Comment: 4 pages, 3 figure
Search for supersymmetric particles in scenarios with a gravitino LSP and stau NLSP
Sleptons, neutralinos and charginos were searched for in the context of
scenarios where the lightest supersymmetric particle is the gravitino. It was
assumed that the stau is the next-to-lightest supersymmetric particle. Data
collected with the DELPHI detector at a centre-of-mass energy near 189 GeV were
analysed combining the methods developed in previous searches at lower
energies. No evidence for the production of these supersymmetric particles was
found. Hence, limits were derived at 95% confidence level.Comment: 31 pages, 14 figure
Prenylation inhibitors stimulate both estrogen receptor α transcriptional activity through AF-1 and AF-2 and estrogen receptor β transcriptional activity
INTRODUCTION: We showed in a previous study that prenylated proteins play a role in estradiol stimulation of proliferation. However, these proteins antagonize the ability of estrogen receptor (ER) α to stimulate estrogen response element (ERE)-dependent transcriptional activity, potentially through the formation of a co-regulator complex. The present study investigates, in further detail, how prenylated proteins modulate the transcriptional activities mediated by ERα and by ERβ. METHODS: The ERE-β-globin-Luc-SV-Neo plasmid was either stably transfected into MCF-7 cells or HeLa cells (MELN cells and HELN cells, respectively) or transiently transfected into MCF-7 cells using polyethylenimine. Cells deprived of estradiol were analyzed for ERE-dependent luciferase activity 16 hours after estradiol stimulation and treatment with FTI-277 (a farnesyltransferase inhibitor) or with GGTI-298 (a geranylgeranyltransferase I inhibitor). In HELN cells, the effect of prenyltransferase inhibitors on luciferase activity was compared after transient transfection of plasmids coding either the full-length ERα, the full-length ERβ, the AF-1-deleted ERα or the AF-2-deleted ERα. The presence of ERα was then detected by immunocytochemistry in either the nuclei or the cytoplasms of MCF-7 cells. Finally, Clostridium botulinum C3 exoenzyme treatment was used to determine the involvement of Rho proteins in ERE-dependent luciferase activity. RESULTS: FTI-277 and GGTI-298 only stimulate ERE-dependent luciferase activity in stably transfected MCF-7 cells. They stimulate both ERα-mediated and ERβ-mediated ERE-dependent luciferase activity in HELN cells, in the presence of and in the absence of estradiol. The roles of both AF-1 and AF-2 are significant in this effect. Nuclear ERα is decreased in the presence of prenyltransferase inhibitors in MCF-7 cells, again in the presence of and in the absence of estradiol. By contrast, cytoplasmic ERα is mainly decreased after treatment with FTI-277, in the presence of and in the absence of estradiol. The involvement of Rho proteins in ERE-dependent luciferase activity in MELN cells is clearly established. CONCLUSIONS: Together, these results demonstrate that prenylated proteins (at least RhoA, RhoB and/or RhoC) antagonize the ability of ERα and ERβ to stimulate ERE-dependent transcriptional activity, potentially acting through both AF-1 and AF-2 transcriptional activities
Structural and functional evolution of the P2Y12-like receptor group
Metabotropic pyrimidine and purine nucleotide receptors (P2Y receptors) belong to the superfamily of G protein-coupled receptors (GPCR). They are distinguishable from adenosine receptors (P1) as they bind adenine and/or uracil nucleotide triphosphates or diphosphates depending on the subtype. Over the past decade, P2Y receptors have been cloned from a variety of tissues and species, and as many as eight functional subtypes have been characterized. Most recently, several members of the P2Y12-like receptor group, which includes the clopidogrel-sensitive ADP receptor P2Y12, have been deorphanized. The P2Y12-like receptor group comprises several structurally related GPCR which, however, display heterogeneous agonist specificity including nucleotides, their derivatives, and lipids. Besides the established function of P2Y12 in platelet activation, expression in macrophages, neuronal and glial cells as well as recent results from functional studies implicate that several members of this group may have specific functions in neurotransmission, inflammation, chemotaxis, and response to tissue injury. This review focuses specifically on the structure-function relation and shortly summarizes some aspects of the physiological relevance of P2Y12-like receptor members
High Tumour Cannabinoid CB1 Receptor Immunoreactivity Negatively Impacts Disease-Specific Survival in Stage II Microsatellite Stable Colorectal Cancer
BACKGROUND: There is good evidence in the literature that the cannabinoid system is disturbed in colorectal cancer. In the present study, we have investigated whether CB(1) receptor immunoreactive intensity (CB(1)IR intensity) is associated with disease severity and outcome. METHODOLOGY/PRINCIPAL FINDINGS: CB(1)IR was assessed in formalin-fixed, paraffin-embedded specimens collected with a consecutive intent during primary tumour surgical resection from a series of cases diagnosed with colorectal cancer. Tumour centre (n = 483) and invasive front (n = 486) CB(1)IR was scored from 0 (absent) to 3 (intense staining) and the data was analysed as a median split i.e. CB(1)IR <2 and ≥2. In microsatellite stable, but not microsatellite instable tumours (as adjudged on the basis of immunohistochemical determination of four mismatch repair proteins), there was a significant positive association of the tumour grade with the CB(1)IR intensity. The difference between the microsatellite stable and instable tumours for this association of CB(1)IR was related to the CpG island methylation status of the cases. Cox proportional hazards regression analyses indicated a significant contribution of CB(1)IR to disease-specific survival in the microsatellite stable tumours when adjusting for tumour stage. For the cases with stage II microsatellite stable tumours, there was a significant effect of both tumour centre and front CB(1)IR upon disease specific survival. The 5 year probabilities of event-free survival were: 85±5 and 66±8%; tumour interior, 86±4% and 63±8% for the CB(1)IR<2 and CB(1)IR≥2 groups, respectively. CONCLUSIONS/SIGNIFICANCE: The level of CB(1) receptor expression in colorectal cancer is associated with the tumour grade in a manner dependent upon the degree of CpG hypermethylation. A high CB(1)IR is indicative of a poorer prognosis in stage II microsatellite stable tumour patients
reaction in an effective Lagrangian model
We investigate the reaction within an effective
Lagrangian model where the contributions to the amplitudes are taken into
account within the tree level. The initial interaction between the two nucleons
is modeled by the exchange of , , and mesons and
the production proceeds via the excitation of the (1650),
(1710), (1720) baryonic resonances. The parameters of the model at
the nucleon-nucleon-meson vertices are determined by fitting the elastic
nucleon-nucleon scattering with an effective interaction based on the exchange
of these four mesons, while those at the resonance vertices are calculated from
the known decay widths of the resonances as well as the vector meson dominance
model. Available experimental data is described well by this approach. The
one-pion-exchange diagram dominates the production process at both higher and
lower beam energies. The and meson exchanges make negligible
contributions. However, the -exchange processes contribute
substantially to the total cross sections at lower beam energies. The
excitation of the (1710) and (1650) resonances dominate this reaction
at beam momenta above and below 3 GeV/c respectively. The interference among
the amplitudes of various resonance excitation processes is significant. For
beam energies very close to the production threshold the hyperon-proton
final state interaction effects are quite important. The data is selective
about the model used to describe the low energy scattering of the two final
state baryons.Comment: Revised version, to appear in Phys. Rev.
Hypoglycemia and the Origin of Hypoxia-Induced Reduction in Human Fetal Growth
The most well known reproductive consequence of residence at high altitude (HA >2700 m) is reduction in fetal growth. Reduced fetoplacental oxygenation is an underlying cause of pregnancy pathologies, including intrauterine growth restriction and preeclampsia, which are more common at HA. Therefore, altitude is a natural experimental model to study the etiology of pregnancy pathophysiologies. We have shown that the proximate cause of decreased fetal growth is not reduced oxygen availability, delivery, or consumption. We therefore asked whether glucose, the primary substrate for fetal growth, might be decreased and/or whether altered fetoplacental glucose metabolism might account for reduced fetal growth at HA.Doppler and ultrasound were used to measure maternal uterine and fetal umbilical blood flows in 69 and 58 residents of 400 vs 3600 m. Arterial and venous blood samples from mother and fetus were collected at elective cesarean delivery and analyzed for glucose, lactate and insulin. Maternal delivery and fetal uptakes for oxygen and glucose were calculated.The maternal arterial – venous glucose concentration difference was greater at HA. However, umbilical venous and arterial glucose concentrations were markedly decreased, resulting in lower glucose delivery at 3600 m. Fetal glucose consumption was reduced by >28%, but strongly correlated with glucose delivery, highlighting the relevance of glucose concentration to fetal uptake. At altitude, fetal lactate levels were increased, insulin concentrations decreased, and the expression of GLUT1 glucose transporter protein in the placental basal membrane was reduced.Our results support that preferential anaerobic consumption of glucose by the placenta at high altitude spares oxygen for fetal use, but limits glucose availability for fetal growth. Thus reduced fetal growth at high altitude is associated with fetal hypoglycemia, hypoinsulinemia and a trend towards lactacidemia. Our data support that placentally-mediated reduction in glucose transport is an initiating factor for reduced fetal growth under conditions of chronic hypoxemia
- …