Suppressed quenching and strong-coupling of Purcell-enhanced single-molecule emission in plasmonic nanocavities

An emitter in the vicinity of a metal nanostructure is quenched by its decay through nonradiative channels, leading to the belief in a zone of inactivity for emitters placed within <10 nm of a plasmonic nanostructure. Here we demonstrate and explain why in tightly coupled plasmonic resonators forming nanocavities “quenching is quenched” due to plasmon mixing. Unlike isolated nanoparticles, such plasmonic nanocavities show mode hybridization, which can massively enhance emitter excitation and decay via radiative channels, here experimentally confirmed by laterally dependent emitter placement through DNA-origami. We explain why this enhancement of excitation and radiative decay can be strong enough to facilitate single-molecule strong coupling, as evident in dynamic Rabi-oscillations

Understanding the plasmonics of nanostructured atomic force microscopy tips

Structured metallic tips are increasingly important for optical spectroscopies such as tip-enhanced Raman spectroscopy, with plasmonic resonances frequently cited as a mechanism for electric field enhancement. We probe the local optical response of sharp and spherical-tipped atomic force microscopy (AFM) tips using a scanning hyperspectral imaging technique to identify the plasmonic behaviour. Localised surface plasmon resonances which radiatively couple with far-field light are found only for spherical AFM tips, with little response for sharp AFM tips, in agreement with numerical simulations of the near-field response. The precise tip geometry is thus crucial for plasmon-enhanced spectroscopies, and the typical sharp cones are not preferred.The authors thank EPSRC Grant Nos. EP/G060649/1, EP/K028510/1, and EP/L027151/1, and ERC Grant No. LINASS 320503 for funding and NanoTools for their services providing Au-coated spherical AFM tips. R.W.B. thanks Queens' College and the Royal Commission for the Exhibition of 1851 for financial support

Plasmonic response and SERS modulation in electrochemical applied potentials

We study the optical response of individual nm-wide plasmonic nanocavities using a nanoparticle-on-mirror design utilised as an electrode in an electrochemical cell. In this geometry Au nanoparticles are separated from a bulk Au film by an ultrathin molecular spacer, giving intense and stable Raman amplification of 100 molecules. Modulation of the plasmonic spectra and the SERS response is observed with an applied voltage under a variety of electrolytes. Different scenarios are discussed to untangle the various mechanisms that can be involved in the electronic interaction between NPs and electrode surfaces.We acknowledge financial support from EPSRC grant EP/G060649/1, EP/L027151/1, EP/G037221/1, EPSRC NanoDTC, and ERC grant LINASS 320503. C. T. was supported by funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement number 609405 (COFUNDPostdocDTU)

Suppressed Quenching and Strong-Coupling of Purcell-Enhanced Single-Molecule Emission in Plasmonic Nanocavities

An emitter in the vicinity of a metal nanostructure is quenched by its decay through nonradiative channels, leading to the belief in a zone of inactivity for emitters placed within <10 nm of a plasmonic nanostructure. Here we demonstrate and explain why in tightly coupled plasmonic resonators forming nanocavities “quenching is quenched” due to plasmon mixing. Unlike isolated nanoparticles, such plasmonic nanocavities show mode hybridization, which can massively enhance emitter excitation and decay via radiative channels, here experimentally confirmed by laterally dependent emitter placement through DNA-origami. We explain why this enhancement of excitation and radiative decay can be strong enough to facilitate single-molecule strong coupling, as evident in dynamic Rabi-oscillations.We acknowledge support from EPSRC Grants EP/G060649/1 and EP/L027151/1 and European Research Council Grant LINASS 320503. N.K. and A.D. contributed equally to this work. R.C. acknowledges support from the Dr. Manmohan Singh scholarship from St. John’s College

Photo-antagonism of the GABAA receptor

Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation

Thermally nucleated magnetic reversal in CoFeB/MgO nanodots

Power consumption is the main limitation in the development of new high performance random access memory for portable electronic devices. Magnetic RAM (MRAM) with CoFeB/MgO based magnetic tunnel junctions (MTJs) is a promising candidate for reducing the power consumption given its non-volatile nature while achieving high performance. The dynamic properties and switching mechanisms of MTJs are critical to understanding device operation and to enable scaling of devices below 30 nm in diameter. Here we show that the magnetic reversal mechanism is incoherent and that the switching is thermally nucleated at device operating temperatures. Moreover, we find an intrinsic thermal switching field distribution arising on the sub-nanosecond time-scale even in the absence of size and anisotropy distributions or material defects. These features represent the characteristic signature of the dynamic properties in MTJs and give an intrinsic limit to reversal reliability in small magnetic nanodevices

Melatonin the "light of night" in human biology and adolescent idiopathic scoliosis

Melatonin "the light of night" is secreted from the pineal gland principally at night. The hormone is involved in sleep regulation, as well as in a number of other cyclical bodily activities and circadian rhythm in humans. Melatonin is exclusively involved in signalling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pacemaker or 'Zeitgeber'. The last decades melatonin has been used as a therapeutic chemical in a large spectrum of diseases, mainly in sleep disturbances and tumours and may play a role in the biologic regulation of mood, affective disorders, cardiovascular system, reproduction and aging. There are few papers regarding melatonin and its role in adolescent idiopathic scoliosis (AIS). Melatonin may play a role in the pathogenesis of scoliosis (neuroendocrine hypothesis) but at present, the data available cannot clearly support this hypothesis. Uncertainties and doubts still surround the role of melatonin in human physiology and pathophysiology and future research is needed

Rasd1 Modulates the Coactivator Function of NonO in the Cyclic AMP Pathway

All living organisms exhibit autonomous daily physiological and behavioural rhythms to help them synchronize with the environment. Entrainment of circadian rhythm is achieved via activation of cyclic AMP (cAMP) and mitogen-activated protein kinase signaling pathways. NonO (p54nrb) is a multifunctional protein involved in transcriptional activation of the cAMP pathway and is involved in circadian rhythm control. Rasd1 is a monomeric G protein implicated to play a pivotal role in potentiating both photic and nonphotic responses of the circadian rhythm. In this study, we have identified and validated NonO as an interacting partner of Rasd1 via affinity pulldown, co-immunoprecipitation and indirect immunofluorescence studies. The GTP-hydrolysis activity of Rasd1 is required for the functional interaction. Functional interaction of Rasd1-NonO in the cAMP pathway was investigated via reporter gene assays, chromatin immunoprecipitation and gene knockdown. We showed that Rasd1 and NonO interact at the CRE-site of specific target genes. These findings reveal a novel mechanism by which the coregulator activity of NonO can be modulated

Treatments for people who use anabolic androgenic steroids: a scoping review.

BACKGROUND: A growing body of evidence suggests that anabolic androgenic steroids (AAS) are used globally by a diverse population with varying motivations. Evidence has increased greatly in recent years to support understanding of this form of substance use and the associated health harms, but there remains little evidence regarding interventions to support cessation and treat the consequences of use. In this scoping review, we identify and describe what is known about interventions that aim to support and achieve cessation of AAS, and treat and prevent associated health problems. METHODS: A comprehensive search strategy was developed in four bibliographic databases, supported by an iterative citation searching process to identify eligible studies. Studies of any psychological or medical treatment interventions delivered in response to non-prescribed use of AAS or an associated harm in any setting were eligible. RESULTS: In total, 109 eligible studies were identified, which included case reports representing a diverse range of disciplines and sources. Studies predominantly focussed on treatments for harms associated with AAS use, with scant evidence on interventions to support cessation of AAS use or responding to dependence. The types of conditions requiring treatment included psychiatric, neuroendocrine, hepatic, kidney, cardiovascular, musculoskeletal and infectious. There was limited evidence of engagement with users or delivery of psychosocial interventions as part of treatment for any condition, and of harm reduction interventions initiated alongside, or following, treatment. Findings were limited throughout by the case report study designs and limited information was provided. CONCLUSION: This scoping review indicates that while a range of case reports describe treatments provided to AAS users, there is scarce evidence on treating dependence, managing withdrawal, or initiating behaviour change in users in any settings. Evidence is urgently required to support the development of effective services for users and of evidence-based guidance and interventions to respond to users in a range of healthcare settings. More consistent reporting in articles of whether engagement or assessment relating to AAS was initiated, and publication within broader health- or drug-related journals, will support development of the evidence base

Effects of circadian disruption on physiology and pathology: from bench to clinic (and back)

Nested within the hypothalamus, the suprachiasmatic nuclei (SCN) represent a central biological clock that regulates daily and circadian (i.e., close to 24 h) rhythms in mammals. Besides the SCN, a number of peripheral oscillators throughout the body control local rhythms and are usually kept in pace by the central clock. In order to represent an adaptive value, circadian rhythms must be entrained by environmental signals or zeitgebers, the main one being the daily light?dark (LD) cycle. The SCN adopt a stable phase relationship with the LD cycle that, when challenged, results in abrupt or chronic changes in overt rhythms and, in turn, in physiological, behavioral, and metabolic variables. Changes in entrainment, both acute and chronic, may have severe consequences in human performance and pathological outcome. Indeed, animal models of desynchronization have become a useful tool to understand such changes and to evaluate potential treatments in human subjects. Here we review a number of alterations in circadian entrainment, including jet lag, social jet lag (i.e., desynchronization between body rhythms and normal time schedules), shift work, and exposure to nocturnal light, both in human subjects and in laboratory animals. Finally, we focus on the health consequences related to circadian/entrainment disorders and propose a number of approaches for the management of circadian desynchronization.Fil: Chiesa, Juan José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Duhart, José Manuel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Casiraghi, Leandro Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paladino, Natalia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bussi, Ivana Leda. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin