88 research outputs found
Resonant excitonic emission of a single quantum dot in the Rabi regime
We report on coherent resonant emission of the fundamental exciton state in a
single semiconductor GaAs quantum dot. Resonant regime with picoseconde laser
excitation is realized by embedding the quantum dots in a waveguiding
structure. As the pulse intensity is increased, Rabi oscillation is observed up
to three periods. The Rabi regime is achieved owing to an enhanced light-matter
coupling in the waveguide. This is due to a \emph{slow light effect}
(), occuring when an intense resonant pulse propagates in a
medium. The resonant control of the quantum dot fundamental transition opens
new possibilities in quantum state manipulation and quantum optics experiments
in condensed matter physics.Comment: Submitted to Phys. Rev. Let
HIPToxâHazard Identification Platform to Assess the Health Impacts from Indoor and Outdoor Air Pollutant Exposures, through Mechanistic Toxicology:A Single-Centre Double-Blind Human Exposure Trial Protocol
Over the past decade, our understanding of the impact of air pollution on short- and long-term population health has advanced considerably, focusing on adverse effects on cardiovascular and respiratory systems. There is, however, increasing evidence that air pollution exposures affect cognitive function, particularly in susceptible groups. Our study seeks to assess and hazard rank the cognitive effects of prevalent indoor and outdoor pollutants through a single-centre investigation on the cognitive functioning of healthy human volunteers aged 50 and above with a familial predisposition to dementia. Participants will all undertake five sequential controlled exposures. The sources of the air pollution exposures are wood smoke, diesel exhaust, cleaning products, and cooking emissions, with clean air serving as the control. Pre- and post-exposure spirometry, nasal lavage, blood sampling, and cognitive assessments will be performed. Repeated testing pre and post exposure to controlled levels of pollutants will allow for the identification of acute changes in functioning as well as the detection of peripheral markers of neuroinflammation and neuronal toxicity. This comprehensive approach enables the identification of the most hazardous components in indoor and outdoor air pollutants and further understanding of the pathways contributing to neurodegenerative diseases. The results of this project have the potential to facilitate greater refinement in policy, emphasizing health-relevant pollutants and providing details to aid mitigation against pollutant-associated health risks
Macroscopic coherence of a single exciton state in a polydiacetylene organic quantum wire
We show that a single exciton state in an individual ordered conjugated
polymer chain exhibits macroscopic quantum spatial coherence reaching tens of
microns, limited by the chain length. The spatial coherence of the k=0 exciton
state is demonstrated by selecting two spatially separated emitting regions of
the chain and observing their interference.Comment: 12 pages with 2 figure
NK3R signalling in the posterodorsal medial amygdala is involved in stress-induced suppression of pulsatile LH secretion in female mice
This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.Psychosocial stress negatively impacts reproductive function by inhibiting pulsatile luteinizing hormone (LH) secretion. The posterodorsal medial amygdala (MePD) is responsible in part for processing stress and modulating the reproductive axis. Activation of the neurokinin 3 receptor (NK3R) suppresses the gonadotropin-releasing hormone (GnRH) pulse generator, under hypoestrogenic conditions, and NK3R activity in the amygdala has been documented to play a role in stress and anxiety. We investigate whether NK3R activation in the MePD is involved in mediating the inhibitory effect of psychosocial stress on LH pulsatility in ovariectomised female mice. First, we administered senktide, an NK3R agonist, into the MePD and monitored the effect on pulsatile LH secretion. We then delivered SB222200, a selective NK3R antagonist, intra-MePD in the presence of predator odour, 2,4,5-trimethylthiazole (TMT) and examined the effect on LH pulses. Senktide administration into the MePD dose-dependently suppresses pulsatile LH secretion. Moreover, NK3R signalling in the MePD mediates TMT-induced suppression of the GnRH pulse generator, which we verified using a mathematical model. The model verifies our experimental findings: (i) predator odour exposure inhibits LH pulses, (ii) activation of NK3R in the MePD inhibits LH pulses and (iii) NK3R antagonism in the MePD blocks stressor-induced inhibition of LH pulse frequency in the absence of ovarian steroids. These results demonstrate for the first time that NK3R neurons in the MePD mediate psychosocial stress-induced suppression of the GnRH pulse generator.Biotechnology and Biological Sciences Research Council (BBSRC)Medical Research Council (MRC
On the exciton binding energy in a quantum well
We consider a model describing the one-dimensional confinement of an exciton
in a symmetrical, rectangular quantum-well structure and derive upper and lower
bounds for the binding energy of the exciton. Based on these bounds, we
study the dependence of on the width of the confining potential with a
higher accuracy than previous reports. For an infinitely deep potential the
binding energy varies as expected from at large widths to at
small widths. For a finite potential, but without consideration of a mass
mismatch or a dielectric mismatch, we substantiate earlier results that the
binding energy approaches the value for both small and large widths,
having a characteristic peak for some intermediate size of the slab. Taking the
mismatch into account, this result will in general no longer be true. For the
specific case of a quantum-well
structure, however, and in contrast to previous findings, the peak structure is
shown to survive.Comment: 32 pages, ReVTeX, including 9 figure
Local disorder and optical properties in V-shaped quantum wires : towards one-dimensional exciton systems
The exciton localization is studied in GaAs/GaAlAs V-shaped quantum wires
(QWRs) by high spatial resolution spectroscopy. Scanning optical imaging of
different generations of samples shows that the localization length has been
enhanced as the growth techniques were improved. In the best samples, excitons
are delocalized in islands of length of the order of 1 micron, and form a
continuum of 1D states in each of them, as evidenced by the sqrt(T) dependence
of the radiative lifetime. On the opposite, in the previous generation of QWRs,
the localization length is typically 50 nm and the QWR behaves as a collection
of quantum boxes. These localization properties are compared to structural
properties and related to the progresses of the growth techniques. The presence
of residual disorder is evidenced in the best samples and explained by the
separation of electrons and holes due to the large in-built piezo-electric
field present in the structure.Comment: 8 figure
Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial
Background & AimsThe Sorafenib Hepatocellular Carcinoma (HCC) Assessment Randomized Protocol (SHARP) trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced HCC. In this trial, 602 patients with well-preserved liver function (>95% ChildâPugh A) were randomized to receive either sorafenib 400mg or matching placebo orally b.i.d. on a continuous basis. Because HCC is a heterogeneous disease, baseline patient characteristics may affect individual responses to treatment. In a comprehensive series of exploratory subgroup analyses, data from the SHARP trial were analyzed to discern if baseline patient characteristics influenced the efficacy and safety of sorafenib.MethodsFive subgroup domains were assessed: disease etiology, tumor burden, performance status, tumor stage, and prior therapy. Overall survival (OS), time to progression (TTP), disease control rate (DCR), and safety were assessed for subgroups within each domain.ResultsSubgroup analyses showed that sorafenib consistently improved median OS compared with placebo, as reflected by hazard ratios (HRs) of 0.50â0.85, similar to the complete cohort (HR=0.69). Sorafenib also consistently improved median TTP (HR, 0.40â0.64), except in HBV-positive patients (HR, 1.03), and DCR. Results are limited by small patient numbers in some subsets. The most common grade 3/4 adverse events included diarrhea, hand-foot skin reaction, and fatigue; the incidence of which did not differ appreciably among subgroups.ConclusionsThese exploratory subgroup analyses showed that sorafenib consistently improved median OS and DCR compared with placebo in patients with advanced HCC, irrespective of disease etiology, baseline tumor burden, performance status, tumor stage, and prior therapy
Oncogenic PIK3CA corrupts growth factor signaling specificity
Pathological activation of the PI3K/AKT pathway is among the most frequent defects in human cancer and is also the cause of rare overgrowth disorders. Yet, there is currently no systematic understanding of the quantitative flow of information within PI3K/AKT signaling and how it is perturbed by disease-causing mutations. Here, we develop scalable, single-cell approaches for systematic analyses of signal processing within the PI3K pathway, enabling precise calculations of its information transfer for different growth factors. Using genetically-engineered human cell models with allele dose-dependent expression of PIK3CAH1047R, we show that this oncogene is not a simple, constitutive pathway activator but a context-dependent modulator of extracellular signal transfer. PIK3CAH1047Rreduces information transmission downstream of IGF1 while selectively enhancing EGF-induced signaling and transcriptional responses. This leads to a gross reduction in signaling specificity, akin to âblurredâ signal perception. The associated increase in signaling heterogeneity promotes phenotypic diversity in a human cervical cancer cell line model and in human induced pluripotent stem cells. Collectively, these findings and the accompanying methodological advances lay the foundations for a systematic mapping of the quantitative mechanisms of PI3K/AKT-dependent signal processing and phenotypic control in health and disease
Modulation of pulsatile GnRH dynamics across the ovarian cycle via changes in the network excitability and basal activity of the arcuate kisspeptin network
This is the author accepted manuscript. The final version is available from eLife Sciences Publications via the DOI in this recordPulsatile GnRH release is essential for normal reproductive function. Kisspeptin secreting neurons found in the arcuate nucleus, known as KNDy neurons for co-expressing neurokinin B, and dynorphin, drive pulsatile GnRH release. Furthermore, gonadal steroids regulate GnRH pulsatile dynamics across the ovarian cycle by altering KNDy neurons' signalling properties. However, the precise mechanism of regulation remains mostly unknown. To better understand these mechanisms we start by perturbing the KNDy system at different stages of the estrous cycle using optogenetics. We find that optogenetic stimulation of KNDy neurons stimulates pulsatile GnRH/LH secretion in estrous mice but inhibits it in diestrous mice. These in-vivo results in combination with mathematical modelling suggest that the transition between estrus and diestrus is underpinned by well-orchestrated changes in neuropeptide signalling and in the excitability of the KNDy population controlled via glutamate signalling. Guided by model predictions, we show that blocking glutamate signalling in diestrous animals inhibits LH pulses, and that optic stimulation of the KNDy population mitigates this inhibition. In estrous mice, disruption of glutamate signalling inhibits pulses generated via sustained low-frequency optic stimulation of the KNDy population, supporting the idea that the level of network excitability is critical for pulse generation. Our results reconcile previous puzzling findings regarding the estradiol-dependent effect that several neuromodulators have on the GnRH pulse generator dynamics. Therefore, we anticipate our model to be a cornerstone for a more quantitative understanding of the pathways via which gonadal steroids regulate GnRH pulse generator dynamics. Finally, our results could inform useful repurposing of drugs targeting the glutamate system in reproductive therapy.Engineering and Physical Sciences Research Council (EPSRC)Biotechnology and Biological Sciences Research Council (BBSRC
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