Restoration of oligodendrocyte pools in a mouse model of chronic cerebral hypoperfusion

Chronic cerebral hypoperfusion, a sustained modest reduction in cerebral blood flow, is associated with damage to myelinated axons and cognitive decline with ageing. Oligodendrocytes (the myelin producing cells) and their precursor cells (OPCs) may be vulnerable to the effects of hypoperfusion and in some forms of injury OPCs have the potential to respond and repair damage by increased proliferation and differentiation. Using a mouse model of cerebral hypoperfusion we have characterised the acute and long term responses of oligodendrocytes and OPCs to hypoperfusion in the corpus callosum. Following 3 days of hypoperfusion, numbers of OPCs and mature oligodendrocytes were significantly decreased compared to controls. However following 1 month of hypoperfusion, the OPC pool was restored and increased numbers of oligodendrocytes were observed. Assessment of proliferation using PCNA showed no significant differences between groups at either time point but showed reduced numbers of proliferating oligodendroglia at 3 days consistent with the loss of OPCs. Cumulative BrdU labelling experiments revealed higher numbers of proliferating cells in hypoperfused animals compared to controls and showed a proportion of these newly generated cells had differentiated into oligodendrocytes in a subset of animals. Expression of GPR17, a receptor important for the regulation of OPC differentiation following injury, was decreased following short term hypoperfusion. Despite changes to oligodendrocyte numbers there were no changes to the myelin sheath as revealed by ultrastructural assessment and fluoromyelin however axon-glial integrity was disrupted after both 3 days and 1 month hypoperfusion. Taken together, our results demonstrate the initial vulnerability of oligodendroglial pools to modest reductions in blood flow and highlight the regenerative capacity of these cells

Multiplex systems for the amplification of short tandem repeat loci: Evaluation of laser fluorescence detection

Short tandem repeat (STR) loci are ideal markers for personal identification and for genomic mapping. Two fluorescent multiplex systems, each designed for simultaneous PCR amplification of four polymorphic STR loci (HUMCSF1PO, HUMTPOX, HUMTH01 and HUMVWFA31, and HUMF13A01, HUMFESFPS, HUMBFXIII and HUMLIPOL), were evaluated on three laser fluorescence detection instruments. Concordant DNA typing results were obtained with all three detection methods. These fluorescent multiplex STR systems offer an accurate, reproducible and versatile method of DNA profiling that is well-suited for forensic identity testing and other genetic analyses

Parameterization of mixed layer eddies. III: Implementation and impact in global ocean climate simulations

A parameterization for the restratification by finite-amplitude, submesoscale, mixed layer eddies, formulated as an overturning streamfunction, has been recently proposed to approximate eddy fluxes of density and other tracers. Here, the technicalities of implementing the parameterization in the coarse-resolution ocean component of global climate models are made explicit, and the primary impacts on model solutions of implementing the parameterization are discussed. Three global ocean general circulation models including this parameterization are contrasted with control simulations lacking the parameterization. The MLE parameterization behaves as expected and fairly consistently in models differing in discretization, boundary layer mixing, resolution, and other parameterizations. The primary impact of the parameterization is a shoaling of the mixed layer, with the largest effect in polar winter regions. Secondary impacts include strengthening the Atlantic meridional overturning while reducing its variability, reducing CFC and tracer ventilation, modest changes to sea surface temperature and air–sea fluxes, and an apparent reduction of sea ice basal melting.National Science Foundation (U.S.) (Grant OCE-0612143)National Science Foundation (U.S.) (Grant OCE-0612059)National Science Foundation (U.S.) (Grant OCE-0825376)National Science Foundation (U.S.) (Grant DMS-0855010)National Science Foundation (U.S.) (Grant OCE-0934737

An approach to construct wave packets with complete classical-quantum correspondence in non-relativistic quantum mechanics

We introduce a method to construct wave packets with complete classical and quantum correspondence in one-dimensional non-relativistic quantum mechanics. First, we consider two similar oscillators with equal total energy. In classical domain, we can easily solve this model and obtain the trajectories in the space of variables. This picture in the quantum level is equivalent with a hyperbolic partial differential equation which gives us a freedom for choosing the initial wave function and its initial slope. By taking advantage of this freedom, we propose a method to choose an appropriate initial condition which is independent from the form of the oscillators. We then construct the wave packets for some cases and show that these wave packets closely follow the whole classical trajectories and peak on them. Moreover, we use de-Broglie Bohm interpretation of quantum mechanics to quantify this correspondence and show that the resulting Bohmian trajectories are also in a complete agreement with their classical counterparts.Comment: 15 pages, 13 figures, to appear in International Journal of Theoretical Physic

Fermionic superfluidity: From high Tc superconductors to ultracold Fermi gases

We present a pairing fluctuation theory which self-consistently incorporates finite momentum pair excitations in the context of BCS--Bose-Einstein condensation (BEC) crossover, and we apply this theory to high $T_c$ superconductors and ultracold Fermi gases. There are strong similarities between Fermi gases in the unitary regime and high Tc superconductors. Here we address key issues of common interest, especially the pseudogap. In the Fermi gases we summarize recent experiments including various phase diagrams (with and without population imbalance), as well as evidence for a pseudogap in thermodynamic and other experiments.Comment: Expanded version, invited talk at the 5th International Conference on Complex Matter -- Stripes 2006, 6 pages, 6 figure

Mean-field description of collapsing and exploding Bose-Einstein condensates

We perform numerical simulation based on the time-dependent mean-field Gross-Pitaevskii equation to understand some aspects of a recent experiment by Donley et al. on the dynamics of collapsing and exploding Bose-Einstein condensates of $^{85}$Rb atoms. They manipulated the atomic interaction by an external magnetic field via a Feshbach resonance, thus changing the repulsive condensate into an attractive one and vice versa. In the actual experiment they changed suddenly the scattering length of atomic interaction from positive to a large negative value on a pre-formed condensate in an axially symmetric trap. Consequently, the condensate collapses and ejects atoms via explosion. We find that the present mean-field analysis can explain some aspects of the dynamics of the collapsing and exploding Bose-Einstein condensates.Comment: 9 Latex pages, 10 ps and eps files, version accepted in Physical Review A, minor changes mad

Noncommutative quantum mechanics and Bohm's ontological interpretation

We carry out an investigation into the possibility of developing a Bohmian interpretation based on the continuous motion of point particles for noncommutative quantum mechanics. The conditions for such an interpretation to be consistent are determined, and the implications of its adoption for noncommutativity are discussed. A Bohmian analysis of the noncommutative harmonic oscillator is carried out in detail. By studying the particle motion in the oscillator orbits, we show that small-scale physics can have influence at large scales, something similar to the IR-UV mixing

Reduction of the value of information sharing as demand becomes strongly auto-correlated

Information sharing has been identified, in the academic literature, as one of the most important levers to mitigate the bullwhip effect in supply chains. A highly-cited article on the bullwhip effect has claimed that the percentage inventory reduction resulting from information sharing in a two level supply chain, when the downstream demand is autoregressive of order one, is an increasing function of the autoregressive parameter of the demand. In this paper we show that this is true only for a certain range of the autoregressive parameter and there is a maximum value beyond which the bullwhip ratio at the upstream stage is reduced and the percentage inventory reduction resulting from information sharing decreases towards zero. We also show that this maximum value of the autoregressive parameter can be as high as 0.7 which represents a common value that may be encountered in many practical contexts. This means that large benefits of information sharing cannot be assumed for those Stock Keeping Units (SKUs) with highly positively auto-correlated demand. Instead, equally careful analysis is needed for these items as for those SKUs with less strongly auto-correlated demand

Cross-National Differences in Victimization : Disentangling the Impact of Composition and Context

Varying rates of criminal victimization across countries are assumed to be the outcome of countrylevel structural constraints that determine the supply ofmotivated o¡enders, as well as the differential composition within countries of suitable targets and capable guardianship. However, previous empirical tests of these ‘compositional’ and ‘contextual’ explanations of cross-national di¡erences have been performed upon macro-level crime data due to the unavailability of comparable individual-level data across countries. This limitation has had two important consequences for cross-national crime research. First, micro-/meso-level mechanisms underlying cross-national differences cannot be truly inferred from macro-level data. Secondly, the e¡ects of contextual measures (e.g. income inequality) on crime are uncontrolled for compositional heterogeneity. In this paper, these limitations are overcome by analysing individual-level victimization data across 18 countries from the International CrimeVictims Survey. Results from multi-level analyses on theft and violent victimization indicate that the national level of income inequality is positively related to risk, independent of compositional (i.e. micro- and meso-level) di¡erences. Furthermore, crossnational variation in victimization rates is not only shaped by di¡erences in national context, but also by varying composition. More speci¢cally, countries had higher crime rates the more they consisted of urban residents and regions with lowaverage social cohesion.

Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy

First published: 16 February 2022Objective: To provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real-world practice, in a broad population of infants with spinal muscular atrophy (SMA). Methods: A prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations. Efficacy assessments included World Health Organisation (WHO) motor milestones, oral and swallowing abilities, and requirements for respiratory support. The implementation of a model of care for onasemnogene abeparvovec administration in health practice is described. Results: 21 children were treated (age range, 0.65–24 months; body weight range, 2.5–12.5 kg) and 19/21 (90.4%) had previous nusinersen. Transient treatment-related side effects occurred in all children; vomiting (100%), transaminitis (57%) and thrombocytopaenia (33%). Incidence of moderate/severe transaminitis was significantly greater in infants weighing ≥8 kg compared with <8 kg (p < 0.05). Duration of prednisolone following treatment was prolonged (mean 87.5 days, range 57–274 days). 16/21 (76%) children gained at least one WHO motor milestone. Stabilisation or improvement in bulbar or respiratory function was observed in 20/21 (95.2%) patients. Implementation challenges were mitigated by developing standard operating procedures and facilitating exchange of knowledge. Interpretation: This study provides real-world evidence to inform treatment decisions and guide therapeutic expectations for onasemnogene abeparvovec and combination therapy for SMA in health practice, especially for children weighing ≥8 kg receiving higher vector loads. Proactive clinical and laboratory surveillance is essential to facilitate individualised management of risks.Arlene M. D’Silva, Sandra Holland, Didu Kariyawasam, Karen Herbert, Peter Barclay, Anita Cairns, Suzanna C. MacLennan, Monique M. Ryan, Hugo Sampaio, Nicholas Smith, Ian R. Woodcock, Eppie M. Yiu, Ian E. Alexander and Michelle A. Farra