Multimodal Imaging of Photoreceptor Structure in Choroideremia

Purpose Choroideremia is a progressive X-linked recessive dystrophy, characterized by degeneration of the retinal pigment epithelium (RPE), choroid, choriocapillaris, and photoreceptors. We examined photoreceptor structure in a series of subjects with choroideremia with particular attention to areas bordering atrophic lesions. Methods Twelve males with clinically-diagnosed choroideremia and confirmed hemizygous mutations in the CHM gene were examined. High-resolution images of the retina were obtained using spectral domain optical coherence tomography (SD-OCT) and both confocal and non-confocal split-detector adaptive optics scanning light ophthalmoscope (AOSLO) techniques. Results Eleven CHM gene mutations (3 novel) were identified; three subjects had the same mutation and one subject had two mutations. SD-OCT findings included interdigitation zone (IZ) attenuation or loss in 10/12 subjects, often in areas with intact ellipsoid zones; RPE thinning in all subjects; interlaminar bridges in the imaged areas of 10/12 subjects; and outer retinal tubulations (ORTs) in 10/12 subjects. Only split-detector AOSLO could reliably resolve cones near lesion borders, and such cones were abnormally heterogeneous in morphology, diameter and density. On split-detector imaging, the cone mosaic terminated sharply at lesion borders in 5/5 cases examined. Split-detector imaging detected remnant cone inner segments within ORTs, which were generally contiguous with a central patch of preserved retina. Conclusions Early IZ dropout and RPE thinning on SD-OCT are consistent with previously published results. Evidence of remnant cone inner segments within ORTs and the continuity of the ORTs with preserved retina suggests that these may represent an intermediate state of retinal degeneration prior to complete atrophy. Taken together, these results supports a model of choroideremia in which the RPE degenerates before photoreceptors

Quantum interference in the field ionization of Rydberg atoms

We excite ultracold rubidium atoms in a magneto-optical trap to a coherent superposition of the three |mj | sublevels of the 37d5/2 Rydberg state. After some delay, during which the relative phases of the superposition components can evolve, we apply an electric field pulse to ionize the Rydberg electron and send it to a detector. The electron traverses many avoided crossings in the Stark levels as it ionizes. The net effect of the transitions at these crossings is to mix the amplitudes of the initial superposition into the same final states at ionization. Similar to a Mach-Zehnder interferometer, the three initial superposition components have multiple paths by which they can arrive at ionization and, since the phases of those paths differ, we observe quantum beats as a function of the delay time between excitation and initiation of the ionization pulse. We present a fully quantum-mechanical calculation of the electron’s path to ionization and the resulting interference pattern

Quantum interference in the field ionization of Rydberg atoms

We excite ultracold rubidium atoms in a magneto-optical trap to a coherent superposition of the three |mj | sublevels of the 37d5/2 Rydberg state. After some delay, during which the relative phases of the superposition components can evolve, we apply an electric field pulse to ionize the Rydberg electron and send it to a detector. The electron traverses many avoided crossings in the Stark levels as it ionizes. The net effect of the transitions at these crossings is to mix the amplitudes of the initial superposition into the same final states at ionization. Similar to a Mach-Zehnder interferometer, the three initial superposition components have multiple paths by which they can arrive at ionization and, since the phases of those paths differ, we observe quantum beats as a function of the delay time between excitation and initiation of the ionization pulse. We present a fully quantum-mechanical calculation of the electron’s path to ionization and the resulting interference pattern

A Rapid Murine Coma and Behavior Scale for Quantitative Assessment of Murine Cerebral Malaria

BACKGROUND: Cerebral malaria (CM) is a neurological syndrome that includes coma and seizures following malaria parasite infection. The pathophysiology is not fully understood and cannot be accounted for by infection alone: patients still succumb to CM, even if the underlying parasite infection has resolved. To that effect, there is no known adjuvant therapy for CM. Current murine CM (MCM) models do not allow for rapid clinical identification of affected animals following infection. An animal model that more closely mimics the clinical features of human CM would be helpful in elucidating potential mechanisms of disease pathogenesis and evaluating new adjuvant therapies. METHODOLOGY/PRINCIPAL FINDINGS: A quantitative, rapid murine coma and behavior scale (RMCBS) comprised of 10 parameters was developed to assess MCM manifested in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA). Using this method a single mouse can be completely assessed within 3 minutes. The RMCBS enables the operator to follow the evolution of the clinical syndrome, validated here by correlations with intracerebral hemorrhages. It provides a tool by which subjects can be identified as symptomatic prior to the initiation of trial treatment. CONCLUSIONS/SIGNIFICANCE: Since the RMCBS enables an operator to rapidly follow the course of disease, label a subject as affected or not, and correlate the level of illness with neuropathologic injury, it can ultimately be used to guide the initiation of treatment after the onset of cerebral disease (thus emulating the situation in the field). The RMCBS is a tool by which an adjuvant therapy can be objectively assessed

Quantum Interference in the Field Ionization of Rydberg Atoms

We excite ultracold rubidium atoms in a magneto-optical trap to a coherent superposition of the three |mj | sublevels of the 37d5/2 Rydberg state. After some delay, during which the relative phases of the superposition components can evolve, we apply an electric field pulse to ionize the Rydberg electron and send it to a detector. The electron traverses many avoided crossings in the Stark levels as it ionizes. The net effect of the transitions at these crossings is to mix the amplitudes of the initial superposition into the same final states at ionization. Similar to a Mach-Zehnder interferometer, the three initial superposition components have multiple paths by which they can arrive at ionization and, since the phases of those paths differ, we observe quantum beats as a function of the delay time between excitation and initiation of the ionization pulse. We present a fully quantum-mechanical calculation of the electron’s path to ionization and the resulting interference pattern

Low dose influenza virus challenge in the ferret leads to increased virus shedding and greater sensitivity to oseltamivir

Ferrets are widely used to study human influenza virus infection. Their airway physiology and cell receptor distribution makes them ideal for the analysis of pathogenesis and virus transmission, and for testing the efficacy of anti-influenza interventions and vaccines. The 2009 pandemic influenza virus (H1N1pdm09) induces mild to moderate respiratory disease in infected ferrets, following inoculation with 106 plaque-forming units (pfu) of virus. We have demonstrated that reducing the challenge dose to 102 pfu delays the onset of clinical signs by 1 day, and results in a modest reduction in clinical signs, and a less rapid nasal cavity innate immune response. There was also a delay in virus production in the upper respiratory tract, this was up to 9-fold greater and virus shedding was prolonged. Progression of infection to the lower respiratory tract was not noticeably delayed by the reduction in virus challenge. A dose of 104 pfu gave an infection that was intermediate between those of the 106 pfu and 102 pfu doses. To address the hypothesis that using a more authentic low challenge dose would facilitate a more sensitive model for antiviral efficacy, we used the well-known neuraminidase inhibitor, oseltamivir. Oseltamivir-treated and untreated ferrets were challenged with high (106 pfu) and low (102 pfu) doses of influenza H1N1pdm09 virus. The low dose treated ferrets showed significant delays in innate immune response and virus shedding, delayed onset of pathological changes in the nasal cavity, and reduced pathological changes and viral RNA load in the lung, relative to untreated ferrets. Importantly, these observations were not seen in treated animals when the high dose challenge was used. In summary, low dose challenge gives a disease that more closely parallels the disease parameters of human influenza infection, and provides an improved pre-clinical model for the assessment of influenza therapeutics, and potentially, influenza vaccines

The Cosmological Probability Density Function for Bianchi Class A Models in Quantum Supergravity

Nicolai's theorem suggests a simple stochastic interpetation for supersymmetric Euclidean quantum theories, without requiring any inner product to be defined on the space of states. In order to apply this idea to supergravity, we first reduce to a one-dimensional theory with local supersymmetry by the imposition of homogeneity conditions. We then make the supersymmetry rigid by imposing gauge conditions, and quantise to obtain the evolution equation for a time-dependent wave function. Owing to the inclusion of a certain boundary term in the classical action, and a careful treatment of the initial conditions, the evolution equation has the form of a Fokker-Planck equation. Of particular interest is the static solution, as this satisfies all the standard quantum constraints. This is naturally interpreted as a cosmological probability density function, and is found to coincide with the square of the magnitude of the conventional wave function for the wormhole state.Comment: 22 pages, Late

Supersymmetric minisuperspace with non-vanishing fermion number

The Lagrangean of $N=1$ supergravity is dimensionally reduced to one (time-like) dimension assuming spatial homogeneity of any Bianchi type within class A of the classification of Ellis and McCallum. The algebra of the supersymmetry generators, the Lorentz generators, the diffeomorphism generators and the Hamiltonian generator is determined and found to close. In contrast to earlier work, infinitely many physical states with non-vanishing even fermion number are found to exist in these models, indicating that minisuperspace models in supergravity may be just as useful as in pure gravity.Comment: 4 page

Language and anxiety: an ethnographic study of international postgraduate students

This paper presents some findings from an ethnographic study of international postgraduate students at a university in the South of England, which involved interviews and participant observation over a twelve-month academic year. One of the major themes that emerged from this research was students’ anxiety over their level of English language. Although all students entered their course with a minimum level of IELTS 6, the majority felt disadvantaged by particularly poor spoken English, and suffered feelings of anxiety, shame and inferiority. Low self-confidence meant that they felt ill-equipped to engage in class discussion and in social interaction which used English as the medium of communication. A common reaction to stress caused by language problems was to retreat into monoethnic communication with students from the same country, further inhibiting progress in language. Whilst some linguistic progress was made by nearly all students during the academic sojourn, the anxiety suffered by students in the initial stage must not be underestimated, and appropriate support systems must be put in place to alleviate their distress