Polarization Dependent Scattering in Cavity Optomagnonics.

The polarization dependence of magnon-photon scattering in an optical microcavity is reported. Because of the short cavity length, the longitudinal mode-matching conditions found in previously explored, large path-length whispering gallery resonators are absent. Nonetheless, for cross-polarized scattering a strong and broadband suppression of one sideband is observed. This arises due to an interference between the Faraday and second-order Cotton-Mouton effects. To fully account for the suppression of the cross-polarized scattering, it is necessary to consider the squeezing of magnon modes intrinsic to thin-film geometry. A copolarized scattering due to Cotton-Mouton effect is also observed. In addition, the magnon modes involved are identified as Damon-Eshbach surface modes, whose nonreciprocal propagation could be exploited in device applications. This Letter experimentally demonstrates the important role of second-order Cotton-Mouton effect for optomagnonic devices.

Fast Gate-Based Readout of Silicon Quantum Dots Using Josephson Parametric Amplification.

Spins in silicon quantum devices are promising candidates for large-scale quantum computing. Gate-based sensing of spin qubits offers a compact and scalable readout with high fidelity, however, further improvements in sensitivity are required to meet the fidelity thresholds and measurement timescales needed for the implementation of fast feedback in error correction protocols. Here, we combine radio-frequency gate-based sensing at 622 MHz with a Josephson parametric amplifier, that operates in the 500-800 MHz band, to reduce the integration time required to read the state of a silicon double quantum dot formed in a nanowire transistor. Based on our achieved signal-to-noise ratio, we estimate that singlet-triplet single-shot readout with an average fidelity of 99.7% could be performed in 1 µs, well below the requirements for fault-tolerant readout and 30 times faster than without the Josephson parametric amplifier. Additionally, the Josephson parametric amplifier allows operation at a lower radio-frequency power while maintaining identical signal-to-noise ratio. We determine a noise temperature of 200 mK with a contribution from the Josephson parametric amplifier (25%), cryogenic amplifier (25%) and the resonator (50%), showing routes to further increase the readout speed.

Triple-Resonant Brillouin Light Scattering in Magneto-Optical Cavities.

An enhancement in Brillouin light scattering of optical photons with magnons is demonstrated in magneto-optical whispering gallery mode resonators tuned to a triple-resonance point. This occurs when both the input and output optical modes are resonant with those of the whispering gallery resonator, with a separation given by the ferromagnetic resonance frequency. The identification and excitation of specific optical modes allows us to gain a clear understanding of the mode-matching conditions. A selection rule due to wave vector matching leads to an intrinsic single-sideband excitation. Strong suppression of one sideband is essential for one-to-one frequency mapping in coherent optical-to-microwave conversion.

Optical spin-transfer-torque-driven domain-wall motion in a ferromagnetic semiconductor.

We demonstrate optical manipulation of the position of a domain wall in a dilute magnetic semiconductor, GaMnAsP. Two main contributions are identified. First, photocarrier spin exerts a spin-transfer torque on the magnetization via the exchange interaction. The direction of the domain-wall motion can be controlled using the helicity of the laser. Second, the domain wall is attracted to the hot spot generated by the focused laser. Unlike magnetic-field-driven domain-wall depinning, these mechanisms directly drive domain-wall motion, providing an optical tweezerlike ability to position and locally probe domain walls.

Immunohistological Description of Nongestational Ovarian Choriocarcinoma in Two Female Mice With Conditional Loss of Trp53 Driven by the Tie2 Promoter.

Nongestational ovarian choriocarcinoma (NGCO) is a tumor of germ cell origin seldom described in nonhuman species. Few spontaneous cases are reported in macaques and mice, with the B6C3F1 strain overrepresented. This report describes 2 cases of ovarian choriocarcinoma in nulliparous female mice with conditional loss of Trp53 under the Tie2 promoter. The mouse line was maintained on a mixed genetic background including Crl: CD1(ICR) and 129X1/SvJ strains. In both cases, affected ovary was partially replaced by blood-filled lacunae lined by neoplastic trophoblast-like giant cells. Immunohistochemically, neoplastic cells expressed folate-binding protein and prolactin and were invariably negative for p53. To the authors' knowledge, this is the first report characterizing this entity in a genetically engineered mouse (GEM) line. Considering that germ cells (the cell population from which NGCO originates) constitutively express Tie2 receptor, it can be speculated that Tie2-driven deletion of Trp53 may have played a role in the development of these tumors.

Inverse conoscopy: a method to measure polarization using patterns generated by a single birefringent crystal.

A method to measure the full polarization vector of a laser beam is proposed and demonstrated. Light is focused onto a birefringent crystal cut such that the slow axis is aligned with the optical axis. The polarization vector of each ray experiences a rotation about the radial axis with a retardation phase dependent on the angle of incidence. Illumination over a wide range of angles applies a range of polarization transforms in parallel that generates a distinct pattern detected by a camera. The input polarization is then inferred from the pattern. The setup uses a single birefringent crystal and involves no moving parts.

Rapid identification of bacteria from bioMérieux BacT/ALERT blood culture bottles by MALDI-TOF MS.

Several studies have reported poor results when trying to identify microorganisms directly from the bioMérieux BacT/ALERT blood culture system using matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) mass spectrometry. The aim of this study is to evaluate two new methods, Sepsityper and an enrichment method for direct identification of microorganisms from this system. For both methods the samples were processed using the Bruker Microflex LT mass spectrometer (Biotyper) using the Microflex Control software to obtain spectra. The results from direct analysis were compared with those obtained by subculture and subsequent identification. A total of 350 positive blood cultures were processed simultaneously by the two methods. Fifty-three cultures were polymocrobial or failed to grow any organism on subculture, and these results were not included as there was either no subculture result, or for polymicrobial cultures it was known that the Biotyper would not be able to distinguish the constituent organisms correctly. Overall, the results showed that, contrary to previous reports, it is possible to identify bacteria directly from bioMérieux blood culture bottles, as 219/297 (74%) correct identifications were obtained using the Bruker Sepsityper method and 228/297 (77%) were obtained for the enrichment method when there is only one organism was present. Although the enrichment method was simpler, the reagent costs for the Sepsityper method were approximately pound 4.00 per sample compared to pound 0.50. An even simpler and cheaper method, which was less labour-intensive and did not require further reagents, was investigated. Seventy-seven specimens from positive signalled blood cultures were analysed by inoculating prewarmed blood agar plates and analysing any growth after 1-, 2- and 4-h periods of incubation at 37 degrees C, by either direct transfer or alcohol extraction. This method gave the highest number of correct identifications, 66/77 (86%), and was cheaper and less labour-intensive than either of the two above methods.

A service evaluation of simultaneous near-patient testing for influenza, respiratory syncytial virus, Clostridium difficile and norovirus in a UK district general hospital.

BACKGROUND: The Cepheid® GeneXpert® (GXP) can simultaneously test for norovirus (NV), Clostridium difficile (CD), influenza A/B (IFA/B) and respiratory syncytial virus (RSV). AIM: To compare centralized multiplex polymerase chain reaction (PCR) testing with localized GXP testing at a district general hospital. METHODS: From December 2017 to December 2018, samples received at Whipps Cross University Hospital (WCUH) were first tested at the local laboratory before transport centrally to the Royal London Hospital (RLH). At the RLH, a non-proprietary multiplex reverse transcriptase (RT) PCR assay was performed, which also tested for gastrointestinal or respiratory pathogens not tested for by the GXP. FINDINGS: A total of 1111 stool and respiratory samples were processed at both sites; 591 were respiratory and 520 were stool samples. Compared to centralized testing, the GXP gave sensitivity, specificity, and NPV all in excess of 97%, with the exception of RSV. The RSV assay had a sensitivity of 66.7% (95% confidence interval (CI) 24.1, 94.0) but an NPV of 99.7% (95% CI 98.6, 99.9). At the RLH, 65 (5.9%) additional respiratory or gastrointestinal viruses were detected, predominantly rhinovirus 35 (3.2%) and adenovirus 11 (1.0%). Compared to centralized testing, the median time saved for local respiratory and gastrointestinal sample testing was 19 h and 46 min and 17 h and 6 min, respectively. CONCLUSIONS: Local GXP testing compared to centralized multiplex PCR testing for IF, NV and CD, demonstrated sensitivities, specificities and NPV between 95% and 100%. Turnaround times were faster, enabling quicker infection prevention and control decision making. In our local setting (WCUH), the GXP demonstrated the potential to reduce NV and IFA/B outbreaks.

The Fps/Fes protein-tyrosine kinase promotes angiogenesis in transgenic mice.

The fps/fes proto-oncogene encodes a cytoplasmic protein-tyrosine kinase known to be highly expressed in hematopoietic cells. To investigate fps/fes biological function, an activating mutation was introduced into the human fps/fes gene which directs amino-terminal myristylation of the Fps/Fes protein. This mutant, myristylated protein induced transformation of Rat-2 fibroblasts. The mutant fps/fes allele was incorporated into the mouse germ line and was found to be appropriately expressed in transgenic mice, in a tissue-specific pattern indistinguishable from that of the endogenous mouse gene. These mice displayed widespread hypervascularity, progressing to multifocal hemangiomas. High levels of both the transgenic human and endogenous murine fps/fes transcripts were detected in vascular tumors by using RNase protection, and fps/fes transcripts were localized to endothelial cells of both the vascular tumors and normal blood vessels by in situ RNA hybridization. Primary human umbilical vein endothelial cultures were also shown to express fps/fes transcripts and the Fps/Fes tyrosine kinase. These results indicate that fps/fes expression is intrinsic to cells of the vascular endothelial lineage and suggest a direct role of the Fps/Fes protein-tyrosine kinase in the regulation of angiogenesis.

The onset of puberty in North American bison (Bison bison) bulls.

Prepubertal testicular development was evaluated in young North American bison (Bison bison) bulls over a 12 months period, by following various parameters of semen quality intended to measure sexual maturity level. The study goals were to characterize bison male reproductive development and to define the age and onset of puberty. Semen was collected by electro-ejaculation from 12 bulls once a month for a period of 12 months, from 13 through 24 months of age. Volume, density, gross motility, individual motility, morphology, live/dead ratio, and concentration were used to judge the quality of the ejaculates. Abnormal sperm were classified into categories according to descriptions used for bovine evaluations and guidelines created by the Western Canadian Association of Bovine Practitioners were used for determining satisfactory semen quality. Minimums of 60% progressive motility and 70% normal sperm cells identified samples as satisfactory. Puberty was defined as the point in testicular development where an ejaculate contains a minimum of 50 x 10(6)sperm cells, showing at least 10% progressive motility. Fecal samples collected from bulls prior to electro-ejaculation for testosterone determination by a commercial testosterone specific antibody radioimmunoassay showed no significant changes in mean fecal testosterone concentrations over time. Changes in mean body weights over the study period were calculated, the average body weight at 13 and 24 months of age were 263+/-18.6 and 475+/-52.2 kg, respectively. Under these experimental conditions, age was determined to be the most significant factor in determining the onset of puberty. On average, bulls reached puberty at 16.5+/-2.5 months. There was a significant increase in the number of normal sperm with increasing bull age as well as significant decreases in proximal cytoplasmic droplets and head defects, but no significant changes in midpiece and principal piece defects. There were significant increases with age in individual progressive motility, gross motility, concentration, density, and volume but not in the percent of live sperm. Bison bulls used for breeding should be capable of passing a breeding soundness evaluation by 24 months of age. The commercial bison industry semen tests, and possibly rejects, many developmentally incomplete bulls between 19 and 21 months of age. We suggest that these may actually be developing normally and should not be hastily discarded; it may be worth testing again at 24 months.

The seasonal fertility of North American bison (Bison bison) bulls.

The objective of this study was to determine the presence and magnitude of seasonal fluctuations in semen quality and other reproductive indices in bison bulls. Testicles from 288 commercially slaughtered bison bulls were collected monthly over a 1-year period. Carcass and testicle weight were determined and measurements of seminiferous tubule lumen, diameter, and epithelial thickness were made. Sperm cell morphology and defects were described and quantified using epididymal semen from each testicle. Twenty-one Plains (Bison bison bison) and Wood bison (Bison bison athabascae) breeding bulls, averaging 6.0 years of age (range 2.5-8.0), from three farms were selected for semen collection and evaluation on the basis of producer co-operation. Semen was collected by electro-ejaculation on four seasonal occasions during a 12-month period. Ejaculate quality was judged on the basis of volume, density, gross and individual motility, morphology, live/dead ratio, and concentration. Sperm cell morphologies were evaluated microscopically and classified according to criteria used for bovine semen. Fecal testosterone was measured at each semen collection using a commercial competitive binding radioimmunoassay. There was an increase in carcass weights over the study period and testis weights were moderately correlated (r=0.44) with carcass weights. However, mean testes weights were heavier (P<0.05) in the summer than in winter, spring, or fall periods. There were no differences in the proportion of normal and abnormal epididymal sperm between seasons but there were seasonal changes in the testicular parenchyma. Seminiferous tubule and lumen diameter, and epithelial thickness were greatest (P<0.05) in summer. Live bulls gained weight between April and November, but lost weight over the winter. Normal sperm cell percentages as well as individual sperm cell motility in electro-ejaculated sperm samples were higher (P<0.05) at the pre-breeding collection relative to other collections, but no change in sperm cell concentrations occurred over the study period. Fecal testosterone concentrations were highest at the pre-breeding period (June) but decreased (P<0.05) in each subsequent collection to reach their lowest levels in the April. While many changes in seen characteristics were not significant, overall results indicate the presence of some reproductive seasonality and increased testicular capacity in the summer breeding season. Bulls showing marginal semen quality in the winter but otherwise carrying desirable genetic traits may warrant another evaluation in late spring prior to being culled from a breeding program.

Fundamentals of pair diffusion in kinematic simulations of turbulence.

We demonstrate that kinematic simulation (KS) of three-dimensional homogeneous turbulence produces fluid element pair statistics in agreement with the predictions of L F. Richardson [Proc. R. Soc. London, Ser. A 110, 709 (1926)] even though KS lacks explicit modeling of turbulent sweeping of small eddies by large ones. This scaling is most clearly evident in the turbulent diffusivity's dependence on rms pair separation and, to a lesser extent, on the pair's travel time statistics. It is also shown that kinematic simulation generates a probability density function of pair separation which is in good agreement with recent theory [S. Goto and J. C. Vassilicos, New J. Phys. 6, 65 (2004)] and with the scaling of the rms pair separation predicted by L. F. Richardson [Proc. R. Soc. London, Ser. A 110, 709 (1926)]. Finally, the statistical persistence hypothesis (SPH) is formulated mathematically and its validity tested in KS. This formulation introduces the concept of stagnation point velocities and relates these to fluid accelerations. The scaling of accelerations found in kinematic simulation supports the SPH, even though KS does not generate a Kolmogorov scaling for the acceleration variance (except for a specific case and a limited range of outer to inner length-scale ratios). An argument is then presented that suggests that the stagnation points in homogeneous isotropic turbulence are on average long-lived.

The induction of ret by Wnt-1 in PC12 cells is atypically dependent on continual Wnt-1 expression.

Wild type PC12 pheochromocytoma cells that had been infected with a Wnt-1-carrying virus and thus express Wnt-1 (PC12/Wnt-1) are known to acquire the same flat cell phenotype as that of spontaneously occurring PC12 flat cell variants except that the latter do not presently express Wnt-1. Flat cell variants of PC12 cells exhibit markedly altered morphology and gene expression. In order to assess the possibility that the spontaneously occurring flat cell variants could have been induced in wild type PC12 cells by previous transient expression of the cell's endogenous Wnt-1, we have isolated PC12/Wnt-1 cells expressing little or no Wnt-1. In spite of absent Wnt-1 expression, they retained their flat cell morphology, glutamate/aspartate transporter activity, increased neu mRNA levels and lack of both norepinephrine transporter activity and nerve growth factor-induced differentiation. Thus, Wnt-1 expression is not required to maintain the flat cell phenotype. However, we identified one gene, ret, whose mRNA level in PC12 was not only increased by Wnt-1 expression, but whose increased mRNA level was also dependent on continual Wnt-1 expression. This finding suggests that the induction of ret by Wnt-1 can be used to elucidate the Wnt-induced signalling pathway in mammalian cells.

Acceleration statistics as measures of statistical persistence of streamlines in isotropic turbulence.

We introduce the velocity Vs of stagnation points as a means to characterize and measure statistical persistence of streamlines. Using theoretical arguments, direct numerical simulations (DNS), and kinematic simulations (KS) of three-dimensional isotropic turbulence for different ratios of inner to outer length scales L/eta of the self-similar range, we show that a frame exists where the average Vs = 0 , that the rms values of acceleration, turbulent fluid velocity, and Vs are related by La'/u'2 approximately (V's/u')(L/eta)(2/3+q) , and that V's/u' approximately (L/eta)q with q = -1/3 in Kolmogorov turbulence, q = -1/6 in current DNS, and q = 0 in our KS. The statistical persistence hypothesis is closely related to the Tennekes sweeping hypothesis.

The physical demands of Super League rugby: Experiences of a newly promoted franchise.

The physical match demands for a newly promoted European Super League (ESL) squad were analysed over a full season using global positioning systems. Players were classified into four positional groups: outside backs (OB), pivots (PIV), middle unit forwards (MUF) and wide running forwards (WRF). MUF covered less total distance (4318 ± 570 m) than WRF (6408 ± 629 m), PIV (6549 ± 853) and OB (7246 ± 333 m) (P < 0.05) and less sprint distance (185 ± 58 m) than WRF (296 ± 82 m), PIV (306 ± 108) and OB (421 ± 89 m; P < 0.05), likely attributable to less playing time by MUF (47.8 ± 6.6 min) compared with WRF (77.0 ± 9.0 min), PIV (72.8 ± 10.6 min) and OB (86.7 ± 3.4 min; P < 0.05). Metres per minute were greater for MUF (90.8 ± 2.2 m.min(-1)) compared with OB (83.6 ± 2.8 m.min(-1)) and WRF (83.4 ± 2.4 m.min(-1); P = 0.001) although not different from PIV (90.2 ± 3.3 m.min(-1); P > 0.05). WRF (36 ± 5) and MUF (35 ± 6) were involved in more collisions than OB (20 ± 3) and PIV (23 ± 3; P < 0.05). The high-speed running and collision demands observed here were greater than that previously reported in the ESL, which may reflect increased demands placed on the lower ranked teams. The present data may be used to inform coaches if training provides the physical stimulus to adequately prepare their players for competition which may be especially pertinent for newly promoted franchises.

From adaptive licensing to adaptive pathways: delivering a flexible life-span approach to bring new drugs to patients.

The concept of adaptive licensing (AL) has met with considerable interest. Yet some remain skeptical about its feasibility. Others argue that the focus and name of AL should be broadened. Against this background of ongoing debate, we examine the environmental changes that will likely make adaptive pathways the preferred approach in the future. The key drivers include: growing patient demand for timely access to promising therapies, emerging science leading to fragmentation of treatment populations, rising payer influence on product accessibility, and pressure on pharma/investors to ensure sustainability of drug development. We also discuss a number of environmental changes that will enable an adaptive paradigm. A life-span approach to bringing innovation to patients is expected to help address the perceived access vs. evidence trade-off, help de-risk drug development, and lead to better outcomes for patients.

Poor compliance is a major factor in unstable outpatient control of anticoagulant therapy.

Control of oral anticoagulant therapy in outpatients is often unsatisfactory. The contribution of poor compliance with prescribed warfarin to unstable anticoagulant control was investigated prospectively using low-dose phenobarbitone as an indicator of compliance in 30 out-patients, 15 with stable and 15 with unstable control. Following entry to the study, there was no significant change in anticoagulation (p = 0.36) in the group with stable control. In the group who previously had unstable control, there was a significant change in INR (p = 0.0045) and anticoagulant control greatly improved. It appears that the considerable fluctuation in INR seen in many of the latter patients before the study was due to poor compliance and that entering them into the study modified their behavior. Two patients in this group who continued to have unstable anticoagulant control were shown to be poorly compliant using the phenobarbitone indicator. The results suggest that, in outpatients, poor compliance is the major cause of unstable anticoagulation with warfarin.

Comparison of effects on sleep of lovastatin and pravastatin in hypercholesterolemia.

The effects on sleep of lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor administered as a lipophilic lactone prodrug, and pravastatin, an inhibitor administered in its active, hydrophilic, open-acid form, were compared by polysomnographic sleep monitoring. Twenty-four men with primary hypercholesterolemia (low-density lipoprotein 4 to 7 mmol/liter) each received 2 of the following 3 treatments in a randomized, incomplete block, crossover design study: lovastatin (40 mg/day), pravastatin (40 mg/day), and placebo. Test drug was administered once daily for 4 weeks during each half of the crossover study. Subjective sleep assessments were obtained throughout each treatment period, and polysomnographic recordings were obtained at the end of the 4-week treatment periods. Treatment periods were separated by a 1-week washout. Lovastatin did not differ from placebo regarding any polysomnographic parameter except "number of entries to wake," for which it produced fewer entries (i.e., change was in the direction of improvement). Pravastatin did not differ from placebo regarding any polysomnographic measures, but was associated with worsening in relation to lovastatin in the following parameters: sleep efficiency, entries to wake, percent rapid eye movement sleep, wake time during sleep, and total wake time. For each of these 4 parameters, although neither drug showed marked differences from placebo, the mean change in the lovastatin group was in the direction of improved sleep, whereas the change in the pravastatin group was in the direction of disturbed sleep. Neither lovastatin nor pravastatin had any effect on subjective, qualitative sleep ratings.(ABSTRACT TRUNCATED AT 250 WORDS)

Scopolamine and benzodiazepine models of dementia: cross-reversals by Ro 15-1788 and physostigmine.

The muscarinic antagonist scopolamine and the benzodiazepine lorazepam both produce transient impairments in memory and attention in normal volunteers. These impairments can be reversed by appropriate agents such as the cholinesterase inhibitor physostigmine in the case of scopolamine or the benzodiazepine antagonist Ro 15-1788 in the case of lorazepam. In this paper we investigated the pharmacological specificity of these reversals by examining the interactions of scopolamine and Ro 15-1788 and of lorazepam and physostigmine. There was no evidence that the effects of scopolamine and lorazepam on cognitive function could be attenuated by Ro 15-1788 and physostigmine, respectively. The results are discussed in terms of pharmacological models of Alzheimer's disease.