Methods of regularization for computing orbits in celestial mechanics

Numerical and analytical methods for orbit computation in celestial mechanics during and beyond collision by introduction of regularized coordinate

Localization of Glycine Receptors in the Human Forebrain, Brainstem, and Cervical Spinal Cord: An Immunohistochemical Review

Inhibitory neurotransmitter receptors for glycine (GlyR) are heteropentameric chloride ion channels that are comprised of four functional subunits, alpha1–3 and beta and that facilitate fast-response, inhibitory neurotransmission in the mammalian brain and spinal cord. We have investigated the distribution of GlyRs in the human forebrain, brainstem, and cervical spinal cord using immunohistochemistry at light and confocal laser scanning microscopy levels. This review will summarize the present knowledge on the GlyR distribution in the human brain using our established immunohistochemical techniques. The results of our immunohistochemical labeling studies demonstrated GlyR immunoreactivity (IR) throughout the human basal ganglia, substantia nigra, various pontine regions, rostral medulla oblongata and the cervical spinal cord present an intense and abundant punctate IR along the membranes of the neuronal soma and dendrites. This work is part of a systematic study of inhibitory neurotransmitter receptor distribution in the human CNS, and provides a basis for additional detailed physiological and pharmacological studies on the inter-relationship of GlyR, GABAAR and gephyrin in the human brain. This basic mapping exercise, we believe, will provide important baselines for the testing of future pharmacotherapies and drug regimes that modulate neuroinhibitory systems. These findings provide new information for understanding the complexity of glycinergic functions in the human brain, which will translate into the contribution of inhibitory mechanisms in paroxysmal disorders and neurodegenerative diseases such as Epilepsy, Huntington's and Parkinson's Disease and Motor Neuron Disease

Latitudinal Differences in the Hibernation Characteristics of Woodchucks (Marmota monax)

There is little information on the phenotypic flexibility of hibernation characteristics within species. To address this issue, we observed differences in hibernation characteristics of three free-ranging populations of woodchucks (Marmota monax) distributed along a latitudinal gradient from Maine to South Carolina. Data from free-ranging animals exhibited a direct relationship between latitude and length of the hibernation season. As expected, woodchucks in the northern latitudes hibernated longer than those in the southern latitudes. Also, the length of interbout arousals decreased with increase in latitude, whereas the length of torpor bouts and the number of arousals increased. Thus, we observed phenotypic plasticity in hibernation characteristics based primarily on latitudinal temperature differences in each population. Further analysis revealed a direct relationship between latitude and total time spent in torpor. Maine animals spent 68% more time in torpor than South Carolina animals. However, total time spent euthermic did not differ among the three populations. The cost-benefit hypothesis of hibernation may help to explain these results. It assumes that hibernators avoid the physiological stress of torpor by staying euthermic as much as possible. Woodchucks in each population maximized time spent euthermic, utilizing torpor only at the level needed to survive winter hibernation and to commence reproduction in the spring

Problem Proposed for the American Mathematical Monthly

The problem is to define: P(x) := {Sigma}{sub k = 1}{sup {infinity}} arctan (x - 1/(k + x + 1) {radical}(k + 1) + (k + 2) {radical}(k + x)). (1) (a) Find explicit, finite-expression evaluations of P(n) for all integers n {ge} 0. (b) Show {tau} := lim{sub x {yields} -1{sup +}} P(x) exists, and find an explicit evaluation for {tau}. (c) Are there a more general closed forms for P, say at half-integers? Solution with the abbreviations: r := {radical} (k + 1), s := {radical} (k + x) the argument of arctan in (1) becomes s{sup 2} - r{sup 2}/(s{sup 2} + 1) r + (r{sup 2} + 1) s = s - r/r s + 1 = 1/r - 1/s / 1 + 1/r 1/s

Kustaanheimo-Stiefel Regularization and the Quadrupolar Conjugacy

In this note, we present the Kustaanheimo-Stiefel regularization in a symplectic and quaternionic fashion. The bilinear relation is associated with the moment map of the $S^{1}$- action of the Kustaanheimo-Stiefel transformation, which yields a concise proof of the symplecticity of the Kustaanheimo-Stiefel transformation symplectically reduced by this circle action. The relation between the Kustaanheimo-Stiefel regularization and the Levi-Civita regularization is established via the investigation of the Levi-Civita planes. A set of Darboux coordinates (which we call Chenciner-F\'ejoz coordinates) is generalized from the planar case to the spatial case. Finally, we obtain a conjugacy relation between the integrable approximating dynamics of the lunar spatial three-body problem and its regularized counterpart, similar to the conjugacy relation between the extended averaged system and the averaged regularized system in the planar case.Comment: 19 pages, corrected versio

Ceftazidime in severe infections: a Swiss multicentre study

A total of 105 patients (mean age 57, range 15 to 90) with serious infections were treated with intravenous ceftazidime, usually 2 g 8-hourly. Most patients had complicating factors such as major surgery, cancer, chronic obstructive lung disease, catheters or anatomical abnormalities. Eighty-seven infectious episodes in 77 patients could be assessed for efficacy. Bacteraemia was diagnosed in 26% of these episodes. Seventy-five per cent of infections were due to Gram-negative bacteria, Pseudomonas aeruginosa being the most frequent. The major sites of infections were the lower respiratory tract (30), the urinary tract (28), the soft tissues (9), the biliary tract (4), bones (4) and the ears (4). Overall, 67% of the patients were cured, 20% improved, 7% relapsed and 6% failed to respond. Among the 27 infections due to Ps aeruginosa, only two failures (in the same patient) and four relapses were recorded. However, in the two failures and in three other cases with persistent Ps. aeruginosa colonisation, the organism had become resistant to ceftazidime. Three failures were recorded in the seven Staphylococcus aureus infections included in this study. Superinfection occurred in four patients. Adverse events included rash (6), Clostridium difficile toxin-induced diarrhoea (3), transaminase elevation (3), weakly positive Coombs test (10). Ceftazidime appears to be safe and effective for the treatment of severe Gram-negative infections, including those caused by Ps. aeruginos

Long-lasting stem cell-like memory CD8+ T cells with a naïve-like profile upon yellow fever vaccination.

Efficient and persisting immune memory is essential for long-term protection from infectious and malignant diseases. The yellow fever (YF) vaccine is a live attenuated virus that mediates lifelong protection, with recent studies showing that the CD8(+) T cell response is particularly robust. Yet, limited data exist regarding the long-term CD8(+) T cell response, with no studies beyond 5 years after vaccination. We investigated 41 vaccinees, spanning 0.27 to 35 years after vaccination. YF-specific CD8(+) T cells were readily detected in almost all donors (38 of 41), with frequencies decreasing with time. As previously described, effector cells dominated the response early after vaccination. We detected a population of naïve-like YF-specific CD8(+) T cells that was stably maintained for more than 25 years and was capable of self-renewal ex vivo. In-depth analyses of markers and genome-wide mRNA profiling showed that naïve-like YF-specific CD8(+) T cells in vaccinees (i) were distinct from genuine naïve cells in unvaccinated donors, (ii) resembled the recently described stem cell-like memory subset (Tscm), and (iii) among all differentiated subsets, had profiles closest to naïve cells. Our findings reveal that CD8(+) Tscm are efficiently induced by a vaccine in humans, persist for decades, and preserve a naïveness-like profile. These data support YF vaccination as an optimal mechanistic model for the study of long-lasting memory CD8(+) T cells in humans

Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich Ataxia

Copyright © 2014 Anjomani Virmouni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Background - Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder, caused by a GAA repeat expansion mutation within intron 1 of the FXN gene. We have previously established and performed preliminary characterisation of several human FXN yeast artificial chromosome (YAC) transgenic FRDA mouse models containing GAA repeat expansions, Y47R (9 GAA repeats), YG8R (90 and 190 GAA repeats) and YG22R (190 GAA repeats). Methodology/Principal Findings - We now report extended cellular, molecular and functional characterisation of these FXN YAC transgenic mouse models. FXN transgene copy number analysis of the FRDA mice demonstrated that the YG22R and Y47R lines each have a single copy of the FXN transgene while the YG8R line has two copies. Single integration sites of all transgenes were confirmed by fluorescence in situ hybridisation (FISH) analysis of metaphase and interphase chromosomes. We identified significant functional deficits, together with a degree of glucose intolerance and insulin hypersensitivity, in YG8R and YG22R FRDA mice compared to Y47R and wild-type control mice. We also confirmed increased somatic GAA repeat instability in the cerebellum and brain of YG22R and YG8R mice, together with significantly reduced levels of FXN mRNA and protein in the brain and liver of YG8R and YG22R compared to Y47R. Conclusions/Significance - Together these studies provide a detailed characterisation of our GAA repeat expansion-based YAC transgenic FRDA mouse models that will help investigations of FRDA disease mechanisms and therapy.European Union, Ataxia UK and FARA