Homogenization of an ensemble of interacting resonant scatterers

We study theoretically the concept of homogenization in optics using an ensemble of randomly distributed resonant stationary atoms with density $\rho$. The ensemble is dense enough for the usual condition for homogenization, viz. $\rho\lambda^3 \gg 1$, to be reached. Introducing the coherent and incoherent scattered powers, we define two criteria to define the homogenization regime. We find that when the excitation field is tuned in a broad frequency range around the resonance, none of the criteria for homogenization is fulfilled, meaning that the condition $\rho\lambda^3\gg 1$ is not sufficient to characterize the homogenized regime around the atomic resonance. We interpret these results as a consequence of the light-induced dipole-dipole interactions between the atoms, which implies a description of scattering in terms of collective modes rather than as a sequence of individual scattering events. Finally, we show that, although homogenization can never be reached for a dense ensemble of randomly positioned laser-cooled atoms around resonance, it becomes possible if one introduces spatial correlations in the positions of the atoms or non-radiative losses, such as would be the case for organic molecules or quantum dots coupled to a phonon bath.Comment: 9 pages, 5 figures. Corrected mistakes in reference

Characterization of a high-power tapered semiconductor amplifier system

We have characterized a semiconductor amplifier laser system which provides up to 200mW output after a single-mode optical fiber at 780nm wavelength. The system is based on a tapered semiconductor gain element, which amplifies the output of a narrow-linewidth diode laser. Gain and saturation are discussed as a function of operating temperature and injection current. The spectral properties of the amplifier are investigated with a grating spectrometer. Amplified spontaneous emission (ASE) causes a spectral background with a width of 4nm FWHM. The ASE background was suppressed to below our detection limit by a proper choice of operating current and temperature, and by sending the light through a single-mode optical fiber. The final ASE spectral density was less than 0.1nW/MHz, i.e. less than 0.2 % of the optical power. Related to an optical transition linewidth of $\Gamma/2\pi=6$ MHz for rubidium, this gives a background suppression of better than -82dB. An indication of the beam quality is provided by the fiber coupling efficiency up to 59 %. The application of the amplifier system as a laser source for atom optical experiments is discussed

Palmitate- and C6 ceramide-induced Tnnt3 pre-mRNA alternative splicing occurs in a PP2A dependent manner

Abstract Background In a previous study, we showed that consumption of diets enriched in saturated fatty acids causes changes in alternative splicing of pre-mRNAs encoding a number of proteins in rat skeletal muscle, including the one encoding skeletal muscle Troponin T (Tnnt3). However, whether saturated fatty acids act directly on muscle cells to modulate alternative pre-mRNA splicing was not assessed. Moreover, the signaling pathway through which saturated fatty acids act to promote changes in alternative splicing is unknown. Therefore, the objective of the present study was to characterize the signaling pathway through which saturated fatty acids act to modulate Tnnt3 alternative splicing. Methods The effects of treatment of L6 myotubes with saturated (palmitate), mono- (oleate), or polyunsaturated (linoleate) fatty acids on alternative splicing of pre-mRNA was assessed using Tnnt3 as a marker gene. Results Palmitate treatment caused a two-fold change (p < 0.05) in L6 myotube Tnnt3 alternative splicing whereas treatment with either oleate or linoleate had minimal effects compared to control myotubes. Treatment with a downstream metabolite of palmitate, ceramide, had effects similar to palmitate on Tnnt3 alternative splicing and inhibition of de novo ceramide biosynthesis blocked the palmitate-induced alternative splicing changes. The effects of palmitate and ceramide on Tnnt3 alternative splicing were accompanied by a 40–50% reduction in phosphorylation of Akt on S473. However, inhibition of de novo ceramide biosynthesis did not prevent palmitate-induced Akt dephosphorylation, suggesting that palmitate may act in an Akt-independent manner to modulate Tnnt3 alternative splicing. Instead, pre-treatment with okadaic acid at concentrations that selectively inhibit protein phosphatase 2A (PP2A) blocked both palmitate- and ceramide-induced changes in Tnnt3 alternative splicing, suggesting that palmitate and ceramide act through PP2A to modulate Tnnt3 alternative splicing. Conclusions Overall, the data show that fatty acid saturation level and ceramides are important factors modulating alternative pre-mRNA splicing through activation of PP2A

Design parameters for a siphon system

DHI are interested in understanding a rather unusual water extraction system that is operated by a water supply company. Typically when water is extracted from the ground a well is dug and a pump is installed in the well to push the water to the surface where it enters a distribution system of pipes. Such a system may consist of a dozen or so wells each connected to a single collection pipe. The system that DHI wish to more fully understand consists of a series of ten wells connected to a single collection pipe. The difference in the mode of operation is that the system contains no pumps in the wells. The force to collect the water comes from placing the end of the collection pipe in a tank that is continuously pumped to keep it at approximately 0.5 bar below atmospheric pressure. In this way the water is drawn out of the wells by a siphon mechanism. Such a system appears cheaper o install with fewer pumps and water supplied in this manner costs roughly half the price of water from a standard pump system. How this multiple siphon system works and how it might be controlled were the general problems of interest to the study group

Larotrectinib efficacy and safety in TRK fusion cancer: An expanded clinical dataset showing consistency in an age and tumor agnostic approach

Background: TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19thFeb 2018. Methods: Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials (NCT02122913, NCT02637687, and NCT02576431) were eligible.Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed using RECIST version 1.1. Results: As of Feb 2018, by independent review, 6 PRs in the PAS deepened to CRs. The median duration of response (DoR) and progression-free survival in the PAS had still not been reached, with 12.9 months median follow-up. At 1 year, 69% of responses were ongoing, 58% of patients remained progression-free and 90% of patients were alive. An additional 19 children and 25 adults (age range, 0.1-78 years) with TRK fusion cancer were enrolled after the PAS, and included cancers of the salivary gland, thyroid, lung, colon, melanoma, sarcoma, GIST and congenital mesoblastic nephroma. In 35 evaluable patients, the ORR by investigator assessment was 74% (5 CR, 21 PR, 6 SD, 2 PD, 1 not determined). In these patients, with median follow-up of 5.5 months, median DoR had not yet been reached, and 88% of responses were ongoing at 6 months, consistent with the PAS. Adverse events (AEs) were predominantly grade 1, with dizziness, increased AST/ALT, fatigue, nausea and constipation the most common AEs reported in ≥ 10% of patients. No AE of grade 3 or 4 related to larotrectinib occurred in more than 5% of patients. Conclusions: TRK fusions are detected in a broad range of tumor types. Larotrectinib is an effective age- and tumor-agnostic treatment for TRK fusion cancer with a positive safety profile. Screening patients for NTRK gene fusions in solid- and brain tumors should be actively considered

Prognostic factors for outcomes of idiopathic sudden sensorineural hearing loss: protocol for the SeaSHeL national prospective cohort study

INTRODUCTION: The mainstay of treatment for idiopathic sudden sensorineural hearing loss (SSNHL) includes oral steroids, intratympanic steroid injections or a combination of both. The National Institute for Health and Care Excellence, in their recent hearing loss guidelines, highlighted the paucity of evidence assessing the comparative effectiveness of these treatments; and the National Institute for Health Research (NIHR) Health Technology Assessment Programme has since released a commissioned call for a trial to identify the most effective route of administration of steroids as a first-line treatment for idiopathic SSNHL. For such trials to be run effectively, reliable information is needed on patients with SSNHL: where they present, numbers, demographics, treatment pathways, as well as outcomes. This study will collect these data in a nationwide cohort study of patients presenting with SSNHL across 97 National Health Service (NHS) trusts. The study will be delivered through ear, nose and throat (ENT) trainee networks, the NIHR Clinical Research Network (CRN) Audiology Champions and the NIHR CRN. Importantly, this study will also provide a dataset to develop a prognostic model to predict recovery for patients with idiopathic SSNHL. The study objectives are to: (1) map the patient pathway and identify the characteristics of adult patients presenting to NHS ENT and hearing services with SSNHL, (2) develop a prognostic model to predict recovery for patients with idiopathic SSNHL and (3) establish the impact of idiopathic SSNHL on patients' quality of life (QoL). METHODS AND ANALYSIS: Study design: national multicentre prospective cohort study across 97 NHS trusts. INCLUSION CRITERIA: adult patients presenting to NHS ENT and hearing services with SSNHL. OUTCOMES: change in auditory function; change in QoL score. ANALYSIS: multivariable prognostic model, using prespecified candidate predictors. Mean change in QoL scores will be calculated from initial presentation to follow-up. ETHICS AND DISSEMINATION: Health Research Authority and NHS Research Ethics Committee approved the study. Publication will be on behalf of study sites and collaborators. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04108598)

An ecological method for the sampling of nonverbal signalling behaviours of young children with profound and multiple learning disabilities (PMLD)

- Background: Profound and multiple learning disabilities (PMLD) are a complex range of disabilities that affect the general health and wellbeing of the individual and their capacity to interact and learn. - Method: We developed a new methodology to capture the nonsymbolic signalling behaviours of children with PMLD within the context of a face-to-face interaction with a caregiver to provide analysis at a micro-level of descriptive detail incorporating the use of the ELAN digital video software. - Conclusion: The signalling behaviours of participants in a natural, everyday interaction can be better understood with the use of this innovation in methodology, which is predicated on the ecology of communication. Recognition of the developmental ability of the participants is an integral factor within that ecology. The method presented establishes an advanced account of the modalities through which a child affected by PMLD is able to communicate