4,333 research outputs found
Quantum measurement characteristics of double-dot single electron transistor
Owing to a few unique advantages, double-dot single electron transistor has
been proposed as an alternative detector for charge states. In this work, we
present a further study for its signal-to-noise property, based on a full
analysis of the setup configuration symmetry. It is found that the
effectiveness of the double-dot detector can approach that of an ideal
detector, if the symmetric capacitive coupling is taken into account. The
quantum measurement efficiency is also analyzed, by comparing the measurement
time with the measurement-induced dephasing time.Comment: 7 pages, 5 figure
Assessing current genetic status of the Hainan gibbon using historical and demographic baselines: implications for conservation management of species of extreme rarity
Evidence-based conservation planning is crucial for informing management decisions for species of extreme rarity, but collection of robust data on genetic status or other parameters can be extremely challenging for such species. The Hainan gibbon, possibly the world's rarest mammal, consists of a single population of c.25 individuals restricted to one protected area on Hainan Island, China, and has persisted for over 30 years at exceptionally low population size. Analysis of genotypes at 11 microsatellite loci from faecal samples for 36% of the current global population and tissue samples from 62% of existing historical museum specimens demonstrates limited current genetic diversity (Na=2.27, Ar=2.24, He =0.43); diversity has declined since the 19th century and even further within the last 30 years, representing declines of c.30% from historical levels (Na=3.36, Ar=3.29, He =0.63). Significant differentiation is seen between current and historical samples (FST =0.156, P=0.0315), and the current population exhibits extremely small Ne (current Ne =2.16). There is evidence for both a recent population bottleneck and an earlier bottleneck, with population size already reasonably low by the late 19th century (historical Ne =1162.96). Individuals in the current population are related at the level of half- to full-siblings between social groups, and full-siblings or parent-offspring within a social group, suggesting that inbreeding is likely to increase in the future. The species' current reduced genetic diversity must be considered during conservation planning, particularly for expectations of likely population recovery, indicating that intensive, carefully planned management is essential
Prevalence of Oral Pain and Barriers to use of Emergency Oral Care Facilities Among Adult Tanzanians.
Oral pain has been the major cause of the attendances in the dental clinics in Tanzania. Some patients postpone seeing the dentist for as long as two to five days. This study determines the prevalence of oral pain and barriers to use of emergency oral care in Tanzania. Questionnaire data were collected from 1,759 adult respondents aged 18 years and above. The study area covered six urban and eight rural study clusters, which had been selected using the WHO Pathfinder methodology. Chi-square tests and logistic regression analyses were performed to identify associations.\ud
Forty two percent of the respondents had utilized the oral health care facilities sometimes in their lifetime. About 59% of the respondents revealed that they had suffered from oral pain and/or discomfort within the twelve months that preceded the study, but only 26.5% of these had sought treatment from oral health care facilities. The reasons for not seeking emergency care were: lack of money to pay for treatment (27.9%); self medication (17.6%); respondents thinking that pain would disappear with time (15.7%); and lack of money to pay for transport to the dental clinic (15.0%). Older adults were more likely to report that they had experienced oral pain during the last 12 months than the younger adults (OR = 1.57, CI 1.07-1.57, P < 0.001). Respondents from rural areas were more likely report dental clinics far from home (OR = 5.31, CI = 2.09-13.54, P < 0.001); self medication at home (OR = 3.65, CI = 2.25-5.94, P < 0.001); and being treated by traditional healer (OR = 5.31, CI = 2.25-12.49, P < 0.001) as reasons for not seeking emergency care from the oral health care facilities than their counterparts from urban areas. Oral pain and discomfort were prevalent among adult Tanzanians. Only a quarter of those who experienced oral pain or discomfort sought emergency oral care from oral health care facilities. Self medication was used as an alternative to using oral care facilities mainly by rural residents. Establishing oral care facilities in rural areas is recommended
Retrograde semaphorin-plexin signalling drives homeostatic synaptic plasticity.
Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease. During neural development, semaphorin-plexin signalling instructs axon guidance and neuronal morphogenesis. However, semaphorins and plexins are also expressed in the adult brain. Here we show that semaphorin 2b (Sema2b) is a target-derived signal that acts upon presynaptic plexin B (PlexB) receptors to mediate the retrograde, homeostatic control of presynaptic neurotransmitter release at the neuromuscular junction in Drosophila. Further, we show that Sema2b-PlexB signalling regulates presynaptic homeostatic plasticity through the cytoplasmic protein Mical and the oxoreductase-dependent control of presynaptic actin. We propose that semaphorin-plexin signalling is an essential platform for the stabilization of synaptic transmission throughout the developing and mature nervous system. These findings may be relevant to the aetiology and treatment of diverse neurological and psychiatric diseases that are characterized by altered or inappropriate neural function and behaviour
Heralded single photon absorption by a single atom
The emission and absorption of single photons by single atomic particles is a
fundamental limit of matter-light interaction, manifesting its quantum
mechanical nature. At the same time, as a controlled process it is a key
enabling tool for quantum technologies, such as quantum optical information
technology [1, 2] and quantum metrology [3, 4, 5, 6]. Controlling both emission
and absorption will allow implementing quantum networking scenarios [1, 7, 8,
9], where photonic communication of quantum information is interfaced with its
local processing in atoms. In studies of single-photon emission, recent
progress includes control of the shape, bandwidth, frequency, and polarization
of single-photon sources [10, 11, 12, 13, 14, 15, 16, 17], and the
demonstration of atom-photon entanglement [18, 19, 20]. Controlled absorption
of a single photon by a single atom is much less investigated; proposals exist
but only very preliminary steps have been taken experimentally such as
detecting the attenuation and phase shift of a weak laser beam by a single atom
[21, 22], and designing an optical system that covers a large fraction of the
full solid angle [23, 24, 25]. Here we report the interaction of single
heralded photons with a single trapped atom. We find strong correlations of the
detection of a heralding photon with a change in the quantum state of the atom
marking absorption of the quantum-correlated heralded photon. In coupling a
single absorber with a quantum light source, our experiment demonstrates
previously unexplored matter-light interaction, while opening up new avenues
towards photon-atom entanglement conversion in quantum technology.Comment: 10 pages, 4 figure
Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer
Background
Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility.
Methods
A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies.
Results
Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001.
Conclusions
Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER
Micro-manufacturing : research, technology outcomes and development issues
Besides continuing effort in developing MEMS-based manufacturing techniques, latest effort in Micro-manufacturing is also in Non-MEMS-based manufacturing. Research and technological development (RTD) in this field is encouraged by the increased demand on micro-components as well as promised development in the scaling down of the traditional macro-manufacturing processes for micro-length-scale manufacturing. This paper highlights some EU funded research activities in micro/nano-manufacturing, and gives examples of the latest development in micro-manufacturing methods/techniques, process chains, hybrid-processes, manufacturing equipment and supporting technologies/device, etc., which is followed by a summary of the achievements of the EU MASMICRO project. Finally, concluding remarks are given, which raise several issues concerning further development in micro-manufacturing
In vitro assessment of the combined effect of eicosapentaenoic acid, green tea extract and curcumin C3 on protein loss in C2C12 myotubes
EPA has been clinically shown to reduce muscle wasting during cancer cachexia. This study investigates whether curcumin or green tea extract (GTE) enhances the ability of low doses of eicosapentaenoic acid (EPA) to reduce loss of muscle protein in an in vitro model. A low dose of EPA with minimal anti-cachectic activity was chosen to evaluate any potential synergistic effect with curcumin or GTE. Depression of protein synthesis and increase in degradation was determined in C2C12 myotubes in response to tumour necrosis factor-α (TNF-α) and proteolysis-inducing factor (PIF). EPA (50 ÎŒM) or curcumin (10 ÎŒg mlâ1) alone had little effect on protein degradation caused by PIF but the combination produced complete inhibition, as did the combination with GTE (10 ÎŒg mlâ1). In response to TNF-α (25 ng mlâ1)-induced protein degradation, EPA had a small, but not significant effect on protein degradation; however, when curcumin and GTE were combined with EPA, the effect was enhanced. EPA completely attenuated the depression of protein synthesis caused by TNF-α, but not that caused by PIF. The combination of EPA with curcumin produced a significant increase in protein synthesis to both agents. GTE alone or in combination with EPA had no effect on the depression of protein synthesis by TNF-α, but did significantly increase protein synthesis in PIF-treated cells. Both TNF-α and PIF significantly reduced myotube diameter from 17 to 13 ÎŒm for TNF-α (23.5%) and 15 ÎŒm (11.8%) for PIF However the triple combination of EPA, curcumin and GTE returned diameters to values not significantly different from the control. These results suggest that either curcumin or GTE or the combination could enhance the anti-catabolic effect of EPA on lean body mass
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