Continuous loading of 1^{1}S0_{0} calcium atoms into an optical dipole trap

We demonstrate an efficient scheme for continuous trap loading based upon spatially selective optical pumping. We discuss the case of $^{1}$S$_{0}$ calcium atoms in an optical dipole trap (ODT), however, similar strategies should be applicable to a wide range of atomic species. Our starting point is a reservoir of moderately cold ($\approx 300 \mu$K) metastable $^{3}$P$_{2}$-atoms prepared by means of a magneto-optic trap (triplet-MOT). A focused 532 nm laser beam produces a strongly elongated optical potential for $^{1}$S$_{0}$-atoms with up to 350 $\mu$K well depth. A weak focused laser beam at 430 nm, carefully superimposed upon the ODT beam, selectively pumps the $^{3}$P$_{2}$-atoms inside the capture volume to the singlet state, where they are confined by the ODT. The triplet-MOT perpetually refills the capture volume with $^{3}$P$_{2}$-atoms thus providing a continuous stream of cold atoms into the ODT at a rate of $10^7$s$^{-1}$. Limited by evaporation loss, in 200 ms we typically load $5 \times 10^5$ atoms with an initial radial temperature of 85 $\mu$K. After terminating the loading we observe evaporation during 50 ms leaving us with $10^5$ atoms at radial temperatures close to 40 $\mu$K and a peak phase space density of $6.8 \times 10^{-5}$. We point out that a comparable scheme could be employed to load a dipole trap with $^{3}$P$_{0}$-atoms.Comment: 4 pages, 4 figure

Detector imperfections in photon-pair source characterization

We analyze how imperfections in single-photon detectors impact the characterization of photon-pair sources. We perform exact calculations to reveal the effects of multi-pair emissions and of noisy, non-unit efficiency, non photon-number resolving detections on the Cauchy-Schwarz parameter, on the second order auto-correlation and cross-correlation functions, and on the visibilities of both Hong-Ou-Mandel and Bell-like interferences. We consider sources producing either two-mode squeezed states or states with a Poissonian photon distribution. The proposed formulas are useful in practice to determine the impacts of multi-pair emissions and dark counts in standard tests used in quantum optics.Comment: 9 pages, 11 figure

Reciprocal space mapping of magnetic order in thick epitaxial MnSi films

We report grazing incidence small angle neutron scattering (GISANS) and complementary off-specular neutron reflectometry (OSR) of the magnetic order in a single-crystalline epitaxial MnSi film on Si(111) in the thick film limit. Providing a means of direct reciprocal space mapping, GISANS and OSR reveal a magnetic modulation perpendicular to the films under magnetic fields parallel and perpendicular to the film, where additional polarized neutron reflectometry (PNR) and magnetization measurements are in excellent agreement with the literature. Regardless of field orientation, our data does not suggest the presence of more complex spin textures, notably the formation of skyrmions. This observation establishes a distinct difference with bulk samples of MnSi of similar thickness under perpendicular field, in which a skyrmion lattice dominates the phase diagram. Extended x-ray absorption fine structure measurements suggest that small shifts of the Si positions within the unstrained unit cell control the magnetic state, representing the main difference between the films and thin bulk samples

Tumor Suppression by Cell Competition Through Regulation of the Hippo Pathway

Homeostatic mechanisms can eliminate abnormal cells to prevent diseases such as cancer. However, the underlying mechanisms of this surveillance are poorly understood. Here we investigated how clones of cells mutant for the neoplastic tumor suppressor gene scribble (scrib) are eliminated from Drosophila imaginal discs. When all cells in imaginal discs are mutant for scrib, they hyperactivate the Hippo pathway effector Yorkie (Yki), which drives growth of the discs into large neoplastic masses. Strikingly, when discs also contain normal cells, the scrib− cells do not overproliferate and eventually undergo apoptosis through JNK-dependent mechanisms. However, induction of apoptosis does not explain how scrib− cells are prevented from overproliferating. We report that cell competition between scrib− and wild-type cells prevents hyperproliferation by suppressing Yki activity in scrib− cells. Suppressing Yki activation is critical for scrib− clone elimination by cell competition, and experimental elevation of Yki activity in scrib−cells is sufficient to fuel their neoplastic growth. Thus, cell competition acts as a tumor-suppressing mechanism by regulating the Hippo pathway in scrib− cells. Animals have evolved homeostatic mechanisms to eliminate abnormal and cancerous cells, protecting the animal from harm (1). A prominent example of an organism removing abnormal cells that have the potential to form tumors is the elimination of scribble mutant (scrib−) cells from Drosophila imaginal discs (2–8). scrib is a conserved tumor-suppressor gene that is essential for the establishment of apical–basal cell polarity (8–10). Scrib is a scaffold protein that localizes to basolateral cell junctions and functions together with the Discs large (Dlg) and Lethal giant larvae (Lgl) adaptor proteins to govern apical–basal cell polarity in epithelial cells (8, 10). Imaginal discs from Drosophila larvae that are homozygous mutant for scrib, dlg, or lgl grow into large tumorous masses of neoplastic cells that display several hallmarks of carcinomas: They lose apical–basal cell polarity, hyperproliferate, and have defects in differentiation (10). Interestingly, the neoplastic phenotype of scrib− cells depends on their cellular environment. When scrib− cells are produced in patches (clones) of mutant cells that are surrounded by normal cells, they do not hyperproliferate, remain small, and eventually are eliminated (2–7, 11–13). Similar effects are observed for lgl− and dlg− clones, although they may not be eliminated very efficiently (11, 14, 15). Thus, the presence of wild-type cells prevents scrib−, lgl−, and dlg−cells from manifesting their tumorigenic potential (2–7, 11–15). Several groups have shown that the JNK stress–response pathway is activated in scrib− clones, leading to engulfment and death or extrusion of mutant cells from the epithelium (2–4, 6, 11, 16). Activation of JNK is required for the elimination of scrib− cells because blocking JNK activity in scrib−cells results in massive overgrowth of clones that is reminiscent of the tumorous overgrowth of entirely mutant discs (2–4, 6, 12, 13). However, blocking apoptosis does not cause overproliferation of scrib− clones (2, 3). Therefore, in addition to inducing apoptosis, JNK suppresses the potential of scrib− cells to hyperproliferate (2, 3). However, how scrib−cells are prevented from hyperproliferating is not known. The presence of normal cells is required for the elimination of tumorigenic scrib− clones because genetically ablating the normal tissue surrounding scrib− cells results in hyperproliferation of the scrib− cells (2, 3). It has been suggested that cell competition, a process by which viable cells of lower fitness are removed from a tissue and replaced through extra proliferation of fitter neighbors (17), is responsible for the elimination of scrib−and lgl− cell clones (2, 14). However, the hypothesis that scrib− and lgl− clones are eliminated by cell competition is in conflict with other reports and thus is controversial. It has been reported that cells with compromised Scrib or Lgl function exhibit elevated activity of Yorkie (Yki), a transcriptional coactivator and downstream effector of the Hippo growth-control pathway (13, 14, 18–20). The Hippo pathway is a conserved tumor-suppressor pathway that suppresses growth by antagonizing the activity of Yki (21). Thus, loss of Hippo pathway activity or elevated levels of Yki activity result in hyperproliferation of imaginal disc cells and resistance to apoptosis that normally would eliminate extra cells (21). Notably, an increase in Yki activity can rescue weak cells, such as cells heterozygous for Minute (M) mutations, from being eliminated by cell competition (22). M mutations occur in ribosomal protein-encoding genes and were the first class of genes identified as having cell-competition phenotypes (23). Homozygous M mutations are lethal, but heterozygous Manimals are viable, although their cells have reduced growth rates (23). In genetic mosaics, however, interaction between wild-type and M+/− cells leads to the elimination of the M+/−cells and expansion of the wild-type population, a phenomenon termed “cell competition” (17). Thus, M+/− cells are less competitive than wild-type cells. Importantly, elevated levels of Yki can rescue M+/− cells from being eliminated by cell competition and also can transform normal cells into supercompetitors that induce apoptosis in their neighbors and proliferate at their neighbors’ expense (22, 24, 25). Yki may increase the competitiveness of cells by inducing the expression of Myc, a known regulator of cell competition (24–27). However, the reports that scrib− cells have high levels of Yki activity and the hypothesis that scrib− cells are eliminated by cell competition present a paradox. If scrib− cells indeed have elevated levels of Yki activity, why does that elevated Yki activity not protect scrib−cells from cell competition? Here we investigated this paradox further. We show that scrib− cells are indeed eliminated by cell competition. We found that for this elimination to occur, scrib− cells undergo a JNK-dependent suppression of Yki activity; this suppression of Yki activity prevents scrib− cells from hyperproliferating and enables their removal. The modulation of Yki activity in scrib−cells thus is a critical effect of the JNK-dependent cell-competition process that removes such tumorigenic cells from imaginal discs. Finally we show that the Myc and Ras oncogenes, which can rescue scrib− clones from elimination (2, 4, 15), do so by conferring competitive fitness to scrib− cells and thereby prevent the down-regulation of Yki activity in scrib− cells. Our results thus further characterize the effects of cell-competition pathways in removing tumorigenic scrib− cells from imaginal discs

Fast-track pathway for elective caesarean section: a quality improvement initiative to promote day 1 discharge.

Enhanced recovery after surgery (ERAS) aims to improve perioperative care, hasten recovery to the normal physiological state and shorten length of stay (LoS). There is evidence that ERAS programmes following elective caesarean section (ELCS) confer benefit through faster return to physiological state and reduced LoS for mother and baby. Baseline audit of ELCS in 2013 revealed a mean LoS of 3 days. We piloted an ERAS discharge pathway promoting day 2 discharge, which rose from 5.0% to 40.2%. 19.2% of women went home on day 1. Many women fed back that they would prefer day 1 discharge. We hypothesised that a day 1 discharge pathway for low-risk women could benefit both women and services at our maternity unit. From October 2015, we developed a 'fast-track pathway' (FTP) using a Plan-Do-Study-Act approach. Between October 2015 and April 2016, we prospectively audited clinical outcomes, LoS and maternal satisfaction from all women placed on the FTP. We held regular multidisciplinary team meetings to allow contemporaneous analysis. Satisfaction was analysed by Likert scale at postoperative surveys. Women were identified in antenatal clinic after meeting predefined low-risk criteria. 27.3% of women (n=131/479) delivering by ELCS entered the FTP. 76.2% of women on the FTP were discharged on day 1. Mean LoS fell to 1.31 days. 94.2% of women who established breast feeding at day 1 were still breast feeding at 7 days. Overall satisfaction at day 7 was 4.71 on a 5-point Likert scale. 73.1% of women reported good pain control. Additional financial savings are estimated at £99 886 annually. There were no related cases of readmission. Day 1 discharge after ELCS is safe and acceptable in carefully selected, low-risk women and has high satisfaction. There may be resultant financial savings and improved flow through a maternity unit with no detected adverse effect on breast feeding, maternal morbidity or postnatal readmissions

Understanding the evolution of catalytically active multi-metal sites in a bifunctional high-entropy alloy electrocatalyst for zinc–air battery application

Zinc–air batteries are known for high theoretical energy density and environmental friendliness. The successful commercial utilization of rechargeable zinc–air batteries is limited by unstable electrochemical interfaces and sluggish kinetics with poor round-trip efficiency. In this study, we report a nanocrystalline high entropy alloy (HEA) comprising Cu–Co–Mn–Ni–Fe (CCMNF) prepared by casting-cum-cryomilling method. This multi-component HEA embodies multiple catalytically active sites with diverse functionalities, thus enhancing the electrochemical redox reactions, e.g., oxygen reduction (ORR) and oxygen evolution reaction (OER). The bifunctional electrocatalytic performance of this HEA is comparable to that of standard catalysts, RuO2 and Pt/C, as evidenced by low overpotential requirements towards OER and ORR. The HEA was tested for use in the air electrode catalyst in the zinc–air battery, where it performed stable oxygen electrocatalysis that was durable over 1045 charging–discharging cycles for ∼90 hours of continuous operation. The microstructural analysis of HEA at different time scales (0, 24, 87 h) during the zinc–air battery operation suggested a dynamic participation of multiple metal active sites on the catalyst surface. Detailed studies revealed that despite leaching in harsh alkaline operation conditions, the synergistic electronic interactions between the component metal sites sustained good electrocatalytic performance and promoted oxygen electrocatalysis through the modification of electronic and chemical properties