Observation of Motion Dependent Nonlinear Dispersion with Narrow Linewidth Atoms in an Optical Cavity

As an alternative to state-of-the-art laser frequency stabilisation using ultra-stable cavities, it has been proposed to exploit the non-linear effects from coupling of atoms with a narrow transition to an optical cavity. Here we have constructed such a system and observed non-linear phase shifts of a narrow optical line by strong coupling of a sample of strontium-88 atoms to an optical cavity. The sample temperature of a few mK provides a domain where the Doppler energy scale is several orders of magnitude larger than the narrow linewidth of the optical transition. This makes the system sensitive to velocity dependent multi-photon scattering events (Dopplerons) that affect the cavity field transmission and phase. By varying the number of atoms and the intra-cavity power we systematically study this non-linear phase signature which displays roughly the same features as for much lower temperature samples. This demonstration in a relatively simple system opens new possibilities for alternative routes to laser stabilization at the sub 100 mHz level and superradiant laser sources involving narrow line atoms. The understanding of relevant motional effects obtained here has direct implications for other atomic clocks when used in relation with ultranarrow clock transitions.Comment: 9 pages (including 4 pages of Supplemental Information), 6 figures. Updated to correspond to the published versio

A modified Oster-Murray-Harris mechanical model of morphogenesis

There are two main modeling paradigms for biological pattern formation in developmental biology: chemical prepattern models and cell aggregation models. This paper focuses on an example of a cell aggregation model, the mechanical model developed by Oster, Murray, and Harris [Development, 78 (1983), pp. 83--125]. We revisit the Oster--Murray--Harris model and find that, due to the infinitesimal displacement assumption made in the original version of this model, there is a restriction on the types of boundary conditions that can be prescribed. We derive a modified form of the model which relaxes the infinitesimal displacement assumption. We analyze the dynamics of this model using linear and multiscale nonlinear analysis and show that it has the same linear behavior as the original Oster--Murray--Harris model. Nonlinear analysis, however, predicts that the modified model will allow for a wider range of parameters where the solution evolves to a bounded steady state. The results from both analyses are verified through numerical simulations of the full nonlinear model in one and two dimensions. The increased range of boundary conditions that are well-posed, as well as a wider range of parameters that yield bounded steady states, renders the modified model more applicable to, and more robust for, comparisons with experiments

Non-linear Spectroscopy of Sr Atoms in an Optical Cavity for Laser Stabilization

We study the non-linear interaction of a cold sample of strontium-88 atoms coupled to a single mode of a low finesse optical cavity in the so-called bad cavity limit and investigate the implications for applications to laser stabilization. The atoms are probed on the weak inter-combination line \lvert 5s^{2} \, ^1 \textrm{S}_0 \rangle \,-\, \lvert 5s5p \, ^3 \textrm{P}_1 \rangle at 689 nm in a strongly saturated regime. Our measured observables include the atomic induced phase shift and absorption of the light field transmitted through the cavity represented by the complex cavity transmission coefficient. We demonstrate high signal-to-noise-ratio measurements of both quadratures - the cavity transmitted phase and absorption - by employing FM spectroscopy (NICE-OHMS). We also show that when FM spectroscopy is employed in connection with a cavity locked to the probe light, observables are substantially modified compared to the free space situation where no cavity is present. Furthermore, the non-linear dynamics of the phase dispersion slope is experimentally investigated and the optimal conditions for laser stabilization are established. Our experimental results are compared to state-of-the-art cavity QED theoretical calculations.Comment: 7 pages, 4 figure

Prosthesis use is associated with reduced physical self-disgust in limb amputees

Self-disgust is an emotion schema negatively affecting people’s body image and is triggered by bodily imperfections and deviations from the “normal” body envelope. In this study, we explore the idea that “normalising” the body in those with limb amputations via the prosthesis would be linked to reduced self-directed disgust. An international clinical community sample (N = 83) with mostly lower limb amputations completed measures about their demographics, prosthesis, adjustment, body image disturbance, psychological distress, and self-directed disgust in a survey design. Consistent with the “normalising” hypothesis, correlation and bootstrapped regression models revealed, first, that frequency of prosthesis use was significantly and negatively associated with physical self-disgust. Second, prosthesis use significantly mediated the exogenous effect of time since amputation on physical self-disgust. These results emphasise the psychological value of the prosthesis beyond its functional use, and stress its importance in normalising the body envelope in those with limb amputations, which may in turn promote psychological well-being

Identifying biological pathways that underlie primordial short stature using network analysis

Mutations in CUL7, OBSL1 and CCDC8, leading to disordered ubiquitination, cause one of the commonest primordial growth disorders, 3-M syndrome. This condition is associated with i) abnormal p53 function, ii) GH and/or IGF1 resistance, which may relate to failure to recycle signalling molecules, and iii) cellular IGF2 deficiency. However the exact molecular mechanisms that may link these abnormalities generating growth restriction remain undefined. In this study, we have used immunoprecipitation/mass spectrometry and transcriptomic studies to generate a 3-M ‘interactome’, to define key cellular pathways and biological functions associated with growth failure seen in 3-M. We identified 189 proteins which interacted with CUL7, OBSL1 and CCDC8, from which a network including 176 of these proteins was generated. To strengthen the association to 3-M syndrome, these proteins were compared with an inferred network generated from the genes that were differentially expressed in 3-M fibroblasts compared with controls. This resulted in a final 3-M network of 131 proteins, with the most significant biological pathway within the network being mRNA splicing/processing. We have shown using an exogenous insulin receptor (INSR) minigene system that alternative splicing of exon 11 is significantly changed in HEK293 cells with altered expression of CUL7, OBSL1 and CCDC8 and in 3-M fibroblasts. The net result is a reduction in the expression of the mitogenic INSR isoform in 3-M syndrome. From these preliminary data, we hypothesise that disordered ubiquitination could result in aberrant mRNA splicing in 3-M; however, further investigation is required to determine whether this contributes to growth failure

Return-to-Play Clinical Milestones: Fail-Rate for Those Claiming to Be Fully Symptom Free

Sport-related concussion remains a concerning public health issue. A multifaceted test battery is recommended for clinical judgments, including return-to-play (RTP). Initiation of RTP testing is based on the athletes\u27 honesty with their current symptoms and is confirmed by the multifaceted test battery. PURPOSE: Examine the rates of test failure in NCAA Division I athletes when they present as being symptom free for 24 hours. METHODS: 36 Division I athletes (18 male, 18 female; avg. age=20.1 years) were evaluated at pre-season baselines (BL), within 48 hours of a diagnosed concussion (CON), and when they reported being symptom free (SF) for 24 hours. At each time point, they were evaluated on a symptom severity score (TS), the vestibular/ocular motor screening (VOMS) exam, and tandem gait (TG) under single-task (ST) and dual-task (DT) conditions (serial-7s subtraction). Neurocognitive testing using the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) was only performed at BL and again if they were clinically clear on the VOMS and TG. Lastly, the Buffalo Concussion Treadmill Test (BCTT) was administered at CON and SF using the standard recommended procedures. Concussions were diagnosed using the international consensus criteria alongside symptom presentation and a mechanism of injury. The fail rate was determined if they presented with one or more of the following: 1) a TS of \u3e7 or physiological symptoms (i.e. headaches, dizziness) not present at BL, 2) VOMS change score \u3e2, 3) NPC \u3e5.0cm, 4) ST outside of 1.5s of their BL, 5) DT outside of 1.7s of their BL, 6) declined ImPACT test results determined by a trained clinician using minimal detectable change score, and 7) symptom provocation during the BCTT. RESULTS: A total of 67% (n=23/36) successfully cleared all the testing criteria and moved onto an RTP protocol once subjectively considered SF. 67% (n=12/18) of females and 61% (n=11/18) of males successfully cleared all the testing at their respective impressions of being SF. The average time from CON to SF was 16.8±16.91 days with no significant difference (p=.56) between males (18.50±17.72 days) and females (15.11±16.41 days). CONCLUSION: These results suggest that a multifaceted concussion assessment battery is heavily warranted to determine the athletes\u27 concussion status and readiness for RTP

Randomized trial comparing proactive, high-dose versus reactive, low-dose intravenous iron supplementation in hemodialysis (PIVOTAL) : Study design and baseline data

Background: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown. Methods: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin 700 μg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 μg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2-4 years. Results: Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry. Conclusions: PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice. Trial Registration: EudraCT number: 2013-002267-25.Peer reviewedFinal Published versio

Curating student learning in a virtual gallery

BACKGROUND The development of digital and creative literacies in biology is ongoing and recent technological advances have reduced the entry barrier for students and staff to engage in the creation of digital artefacts. We have developed a platform based on the Unity game engine that allows students to create virtual galleries in which they can curate 3D exhibitions of their learning which can be viewed on either a flat screen or a virtual reality headset. As part of the instructional activities, students are introduced to Object-Based Learning pedagogy by museum curators. THE VIRTUAL GALLERY Following a series of workshops to learn the basics of Unity, 500 first-year human biology students (in groups of 5) used templates to create their own virtual galleries, populating them with objects from all aspects of their studies from lectures to practicals and masterclasses. These galleries demonstrated the students’ mastery of the basics of working in and navigating virtual environments. This represents a unique way to collaboratively curate evidence of their learning across the semester and to communicate that understanding to a general audience. This is a new and novel approach to developing digital literacies and a portfolio of achievement in undergraduate science students

A mathematical model for fibro-proliferative wound healing disorders

The normal process of dermal wound healing fails in some cases, due to fibro-proliferative disorders such as keloid and hypertrophic scars. These types of abnormal healing may be regarded as pathologically excessive responses to wounding in terms of fibroblastic cell profiles and their inflammatory growth-factor mediators. Biologically, these conditions are poorly understood and current medical treatments are thus unreliable. In this paper, the authors apply an existing deterministic mathematical model for fibroplasia and wound contraction in adult mammalian dermis (Olsenet al., J. theor. Biol. 177, 113–128, 1995) to investigate key clinical problems concerning these healing disorders. A caricature model is proposed which retains the fundamental cellular and chemical components of the full model, in order to analyse the spatiotemporal dynamics of the initiation, progression, cessation and regression of fibro-contractive diseases in relation to normal healing. This model accounts for fibroblastic cell migration, proliferation and death and growth-factor diffusion, production by cells and tissue removal/decay. Explicit results are obtained in terms of the model processes and parameters. The rate of cellular production of the chemical is shown to be critical to the development of a stable pathological state. Further, cessation and/or regression of the disease depend on appropriate spatiotemporally varying forms for this production rate, which can be understood in terms of the bistability of the normal dermal and pathological steady states—a central property of the model, which is evident from stability and bifurcation analyses. The work predicts novel, biologically realistic and testable pathogenic and control mechanisms, the understanding of which will lead toward more effective strategies for clinical therapy of fibro-proliferative disorders