Coherence build up and laser thresholds from nanolasers to macroscopic lasers

We detail the derivation of nanolaser models that include coherent and incoherent variables and predict the existence of a laser threshold, irrespective of cavity size and emitter number, for both single- and multi-electron systems. The growth in photon number in the lasing mode is driven by an increase in correlation between absorption and emission processes, leading to the onset of self-sustained stimulated emission (laser threshold), followed, in turn, by a correlation decrease and ending with the dominance of coherent emission. The first-order coherence $g^{(1)}$ steadily increases, as the pump grows towards the laser threshold value, and reaches unity at or beyond threshold. The transition toward coherent emission becomes increasingly sharp as the number of emitters and of the coupled electromagnetic cavity modes increase, continuously connecting, in the thermodynamic limit, the physics of nano- and macroscopic lasers at threshold. Our predictions are in remarkable agreement with experiments whose first-order coherence measurements have so far been explained only phenomenologically. A consistent evaluation of different threshold indicators provides a tool for a correct interpretation of experimental measurements at the onset of laser action.Comment: 11 pages, 5 figure

Photon-number squeezing in nano- and microlasers

Based on theoretical predictions on the appearance of antibunching before the laser threshold at the nano- and microscale, we analyze the amount of photon-number squeezing naturally produced in the laser emission. Up to 3 dB photon number noise reduction is obtained in comparison with the coherent emission, with output power in the range of pW and with negligible effects due to pump fluctuations. The scheme requires a moderately high Q cavity and holds promise for the construction of a simple and effective photon-number squeezed source

A Search for Light Hydrides in the Envelopes of Evolved Stars

We report a search for the diatomic hydrides SiH, PH, and FeH along the line of sight toward the chemically rich circumstellar envelopes of IRC+10216 and VY Canis Majoris. These molecules are thought to form in high temperature regions near the photospheres of these stars, and may then further react via gas-phase and dust-grain interactions leading to more complex species, but have yet to be constrained by observation. We used the GREAT spectrometer on SOFIA to search for rotational emission lines of these molecules in four spectral windows ranging from 600 GHz to 1500 GHz. Though none of the targeted species were detected in our search, we report their upper limit abundances in each source and discuss how they influence the current understanding of hydride chemistry in dense circumstellar media. We attribute the non-detections of these hydrides to their compact source sizes, high barriers of formation, and proclivity to react with other molecules in the winds.Comment: Accepted for publication in ApJ. 14 pages, 4 figures, 3 table

Cost-efficient nanoscopy reveals nanoscale architecture of liver cells and platelets

Single-molecule localization microscopy (SMLM) provides a powerful toolkit to specifically resolve intracellular structures on the nanometer scale, even approaching resolution classically reserved for electron microscopy (EM). Although instruments for SMLM are technically simple to implement, researchers tend to stick to commercial microscopes for SMLM implementations. Here we report the construction and use of a “custom-built” multi-color channel SMLM system to study liver sinusoidal endothelial cells (LSECs) and platelets, which costs significantly less than a commercial system. This microscope allows the introduction of highly affordable and low-maintenance SMLM hardware and methods to laboratories that, for example, lack access to core facilities housing high-end commercial microscopes for SMLM and EM. Using our custom-built microscope and freely available software from image acquisition to analysis, we image LSECs and platelets with lateral resolution down to about 50 nm. Furthermore, we use this microscope to examine the effect of drugs and toxins on cellular morphology

Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson’s disease

An increase in the efficiency of clinical trial conduct has been successfully demonstrated in the oncology field, by the use of multi-arm, multi-stage trials allowing the evaluation of multiple therapeutic candidates simultaneously, and seamless recruitment to phase 3 for those candidates passing an interim signal of efficacy. Replicating this complex innovative trial design in diseases such as Parkinson’s disease is appealing, but in addition to the challenges associated with any trial assessing a single potentially disease modifying intervention in Parkinson’s disease, a multiarm platform trial must also specifically consider the heterogeneous nature of the disease, alongside the desire to potentially test multiple treatments with different mechanisms of action. In a multi-arm trial, there is a need to appropriately stratify treatment arms to ensure each are comparable with a shared placebo/standard of care arm; however, in Parkinson’s disease there may be a preference to enrich an arm with a subgroup of patients that may be most likely to respond to a specific treatment approach. The solution to this conundrum lies in having clearly defined criteria for inclusion in each treatment arm as well as an analysis plan that takes account of predefined subgroups of interest, alongside evaluating the impact of each treatment on the broader population of Parkinson’s disease patients. Beyond this, there must be robust processes of treatment selection, and consensus derived measures to confirm target engagement and interim assessments of efficacy, as well as consideration of the infrastructure needed to support recruitment, and the long-term funding and sustainability of the platform. This has to incorporate the diverse priorities of clinicians, triallists, regulatory authorities and above all the views of people with Parkinson’s disease.</p

UK vaccines network:Mapping priority pathogens of epidemic potential and vaccine pipeline developments

During the 2013–2016 Ebola outbreak in West Africa an expert panel was established on the instructions of the UK Prime Minister to identify priority pathogens for outbreak diseases that had the potential to cause future epidemics. A total of 13 priority pathogens were identified, which led to the prioritisation of spending in emerging diseases vaccine research and development from the UK. This meeting report summarises the process used to develop the UK pathogen priority list, compares it to lists generated by other organisations (World Health Organisation, National Institutes of Allergy and Infectious Diseases) and summarises clinical progress towards the development of vaccines against priority diseases. There is clear technical progress towards the development of vaccines. However, the availability of these vaccines will be dependent on sustained funding for clinical trials and the preparation of clinically acceptable manufactured material during inter-epidemic periods

Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson’s disease

An increase in the efficiency of clinical trial conduct has been successfully demonstrated in the oncology field, by the use of multi-arm, multi-stage trials allowing the evaluation of multiple therapeutic candidates simultaneously, and seamless recruitment to phase 3 for those candidates passing an interim signal of efficacy. Replicating this complex innovative trial design in diseases such as Parkinson’s disease is appealing, but in addition to the challenges associated with any trial assessing a single potentially disease modifying intervention in Parkinson’s disease, a multiarm platform trial must also specifically consider the heterogeneous nature of the disease, alongside the desire to potentially test multiple treatments with different mechanisms of action. In a multi-arm trial, there is a need to appropriately stratify treatment arms to ensure each are comparable with a shared placebo/standard of care arm; however, in Parkinson’s disease there may be a preference to enrich an arm with a subgroup of patients that may be most likely to respond to a specific treatment approach. The solution to this conundrum lies in having clearly defined criteria for inclusion in each treatment arm as well as an analysis plan that takes account of predefined subgroups of interest, alongside evaluating the impact of each treatment on the broader population of Parkinson’s disease patients. Beyond this, there must be robust processes of treatment selection, and consensus derived measures to confirm target engagement and interim assessments of efficacy, as well as consideration of the infrastructure needed to support recruitment, and the long-term funding and sustainability of the platform. This has to incorporate the diverse priorities of clinicians, triallists, regulatory authorities and above all the views of people with Parkinson’s disease.</p

The Chandra Deep Wide-field Survey: A New Chandra Legacy Survey in the Boötes Field. I. X-Ray Point Source Catalog, Number Counts, and Multiwavelength Counterparts

We present a new, ambitious survey performed with the Chandra X-ray Observatory of the 9.3 deg2 Boötes field of the NOAO Deep Wide-Field Survey. The wide field probes a statistically representative volume of the universe at high redshift. The Chandra Deep Wide-field Survey exploits the excellent sensitivity and angular resolution of Chandra over a wide area, combining 281 observations spanning 15 yr, for a total exposure time of 3.4 Ms, and detects 6891 X-ray point sources down to limiting fluxes of 4.7 × 10−16, 1.5 × 10−16, and 9 ×10−16 erg cm−2 s−1 in the 0.5–7, 0.5–2, and 2–7 keV bands, respectively. The robustness and reliability of the detection strategy are validated through extensive, state-of-the-art simulations of the whole field. Accurate number counts, in good agreement with previous X-ray surveys, are derived thanks to the uniquely large number of point sources detected, which resolve 65.0% ± 12.8% of the cosmic X-ray background between 0.5 and 2 keV and 81.0% ± 11.5% between 2 and 7 keV. Exploiting the wealth of multiwavelength data available on the field, we assign redshifts to ~94% of the X-ray sources, estimate their obscuration, and derive absorption-corrected luminosities. We provide an electronic catalog containing all of the relevant quantities needed for future investigations