Intranasal sodium citrate solution improves olfaction in post-viral hyposmia

Background: Calcium plays an integral role in olfactory signal transduction, including feedback inhibition. Sodium citrate acts as a calcium sequestrant and when applied intranasally, reduces free calcium available for feedback inhibition, which should theoretically improve olfaction. We aimed to investigate the utility of intranasal sodium citrate in improving the olfactory function of hyposmic patients, by performing this prospective placebo controlled, single-blinded trial. Methodology: Monorhinal olfactory testing for odour identification and threshold was performed in hyposmic patients using “Sniffin’ Sticks”, before and after treatment. Treatment consisted of sodium citrate solution application to the olfactory cleft. Sodium chloride solution was applied to the contralateral olfactory cleft, which therefore acted as placebo control. Patients were blinded to the side of sodium citrate application, and side of treatment was randomized between patients. Results: 57 patients participated in the trial, aged 22-79. Causes of hyposmia included: post-viral (7); posttraumatic (10); sinonasal (30) and idiopathic (10). Compared with placebo, there was significant improvement in the identification scores of participants with post-viral hyposmia, following sodium citrate treatment. No significant change in olfactory function occurred for either identification or threshold in any other aetiological subgroup. Conclusions: Intranasal sodium citrate may be of benefit to patients with post-viral hyposmia

Behavioral and other phenotypes in a cytoplasmic Dynein light intermediate chain 1 mutant mouse

The cytoplasmic dynein complex is fundamentally important to all eukaryotic cells for transporting a variety of essential cargoes along microtubules within the cell. This complex also plays more specialized roles in neurons. The complex consists of 11 types of protein that interact with each other and with external adaptors, regulators and cargoes. Despite the importance of the cytoplasmic dynein complex, we know comparatively little of the roles of each component protein, and in mammals few mutants exist that allow us to explore the effects of defects in dynein-controlled processes in the context of the whole organism. Here we have taken a genotype-driven approach in mouse (Mus musculus) to analyze the role of one subunit, the dynein light intermediate chain 1 (Dync1li1). We find that, surprisingly, an N235Y point mutation in this protein results in altered neuronal development, as shown from in vivo studies in the developing cortex, and analyses of electrophysiological function. Moreover, mutant mice display increased anxiety, thus linking dynein functions to a behavioral phenotype in mammals for the first time. These results demonstrate the important role that dynein-controlled processes play in the correct development and function of the mammalian nervous system

Energy-momentum diffusion from spacetime discreteness

We study potentially observable consequences of spatiotemporal discreteness for the motion of massive and massless particles. First we describe some simple intrinsic models for the motion of a massive point particle in a fixed causal set background. At large scales, the microscopic swerves induced by the underlying atomicity manifest themselves as a Lorentz invariant diffusion in energy-momentum governed by a single phenomenological parameter, and we derive in full the corresponding diffusion equation. Inspired by the simplicity of the result, we then derive the most general Lorentz invariant diffusion equation for a massless particle, which turns out to contain two phenomenological parameters describing, respectively, diffusion and drift in the particle's energy. The particles do not leave the light cone however: their worldlines continue to be null geodesics. Finally, we deduce bounds on the drift and diffusion constants for photons from the blackbody nature of the spectrum of the cosmic microwave background radiation.Comment: 13 pages, 4 figures, corrected minor typos and updated to match published versio

A Mini-PET beamline for optimized proton delivery to the ISOTRACE™ target system

Introduction The ISOTRACE™ Super-Conducting Cyclotron is PMB-Alcen’s redeveloped and modernized version of Oxford Instrument’s OSCAR superconducting cyclotron [1]. Its extracted 80+ mi-croamperes of 12 MeV protons are used for the production of PET radioisotopes. Following the philosophy of Dickie, Stevenson, Szlavik [2] for minimizing dose to personnel, and as developed by Dehnel et al [3,4], and Stokely et al [5], the ISOTRACE™ shall utilize an innovative, light-weight, integrated and self-supporting Mini-Beamline. This permits the relatively high residual radiation fields around PET targets to be moved ~1 metre away from the cyclotron, and facilitates the use of local shielding (around the targets) that limits prompt gammas and neutrons, but more importantly attenuates the residual target radiation, so that maintenance/research staff can work on the cyclotron in a relatively low activity environment. In addition, the mini-beamline for PET utilizes a compound quadrupole/steerer doublet that permits active and dynamic focusing/steering of the extracted proton beam for optimized production and minimized losses [3], so it improves on the successful work of Theroux et al [6]. The integrated beamline unit is extremely small, so that it is very unlike bulky traditional PET and SPECT beamlines that require substantial support structures, such as described by Dehnel in [7,8]. Material and Methods The ISOTRACE™ cyclotron is pictured in FIG. 1. The exit port flange and gate valve to which the integrated mini-beamline for PET shall be mounted is shown. Immediately upstream of the exit port, hidden from view, is a 4 jaw collimator (called BPI for Beam Position Indicator) with spilled beam current readbacks to the control system. TABLE 1 shows the nominal beam emittance and Twiss parameter values at the exit port flange location. This ion-optical information is necessary to simulate ion beam transport, develop the mini-beamline, and determine a nominal tune (i.e. magnet settings). Results and Conclusion TABLE 2 shows the ion-optical system parameters. FIGS. 2 and 3 show the horizontal and vertical beam profiles. The Horizontally focusing Quadrupole magnet (HQ), and Vertically focusing Quadrupole magnet (VQ) aperture diameter, 33 mm, was chosen to give sufficient beam acceptance. The focusing strength is a function of BL, so the effective length, L = 150 mm, was chosen to ensure Bmax less than 0.3 Tesla, while keeping overall magnet mass down. The quad-rupole magnets are fitted with water-cooled compound coils in which the copper/mylar strip wound portion of each coil is a winding for the quadrupole focusing function, and the wire wound portion is for the steering function. To increase beam acceptance and provide additional section strength for the pipe support function, the internal aperture of the low-activation aluminium beam pipe and the external shape are in the shape of a cross. FIG. 4 shows the beam crosssection at the mid-point of the downstream quadrupole magnet, and illustrates the additional acceptance as compared to a round beampipe. In order to machine the interior profile, the pipe is comprised of two premachined pieces that are friction stirwelded together. FIG. 5 is an isometric of the mini-beamline for PET. The four upstream HQ compound coils are excited with a 75A power supply for the horizontally focusing quadrupole magnet function, and a ± 10A power supply for a vertical steering function. The same power supplies are used for the four downstream VQ compound coils for the purpose of a vertically focusing quadrupole magnet function and horizontal steering function

Polarization Diffusion from Spacetime Uncertainty

A model of Lorentz invariant random fluctuations in photon polarization is presented. The effects are frequency dependent and affect the polarization of photons as they propagate through space. We test for this effect by confronting the model with the latest measurements of polarization of Cosmic Microwave Background (CMB) photons.Comment: 4 pages, 1 figur

Thomas rotation and Thomas precession

Exact and simple calculation of Thomas rotation and Thomas precessions along a circular world line is presented in an absolute (coordinate-free) formulation of special relativity. Besides the simplicity of calculations the absolute treatment of spacetime allows us to gain a deeper insight into the phenomena of Thomas rotation and Thomas precession.Comment: 20 pages, to appear in Int. J. Theo. Phy

Does quantum mechanics tell an atomistic spacetime?

The canonical answer to the question posed is "Yes." -- tacitly assuming that quantum theory and the concept of spacetime are to be unified by `quantizing' a theory of gravitation. Yet, instead, one may ponder: Could quantum mechanics arise as a coarse-grained reflection of the atomistic nature of spacetime? -- We speculate that this may indeed be the case. We recall the similarity between evolution of classical and quantum mechanical ensembles, according to Liouville and von Neumann equation, respectively. The classical and quantum mechanical equations are indistinguishable for objects which are free or subject to spatially constant but possibly time dependent, or harmonic forces, if represented appropriately. This result suggests a way to incorporate anharmonic interactions, including fluctuations which are tentatively related to the underlying discreteness of spacetime. Being linear and local at the quantum mechanical level, the model offers a decoherence and natural localization mechanism. However, the relation to primordial deterministic degrees of freedom is nonlocal.Comment: Based on invited talks at Fourth International Workshop DICE2008, held at Castello Pasquini / Castiglioncello, Italy, 22-26 September 2008 and at DISCRETE'08 - Symposium on Prospects in the Physics of Discrete Symmetries, held at IFIC, Valencia, Spain, 11-16 December 2008 - to appear in respective volumes of Journal of Physics: Conference Serie

Normal levels of p27Xic1 are necessary for somite segmentation and determining pronephric organ size

The Xenopus laevis cyclin dependent kinase inhibitor p27Xic1 has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27Xic1 is expressed in the developing kidney in the nephrostomal regions. Using over-expression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27Xic1 regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27Xic1 expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27Xic1 are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27Xic1, and reveal its differentiation function is not universally utilised in all developing tissues