Production, Collection and Utilization of Very Long-Lived Heavy Charged Leptons

If a fourth generation of leptons exists, both the neutrino and its charged partner must be heavier than 45 GeV. We suppose that the neutrino is the heavier of the two, and that a global or discrete symmetry prohibits intergenerational mixing. In that case, non-renormalizable Planck scale interactions will induce a very small mixing; dimension five interactions will lead to a lifetime for the heavy charged lepton of $O(1-100)$ years. Production of such particles is discussed, and it is shown that a few thousands can be produced and collected at a linear collider. The possible uses of these heavy leptons is also briefly discussed.Comment: 9 pages Late

Studies of superconducting materials with muon spin rotation

The muon spin rotation/relaxation technique was found to be an exceptionally effective means of measuring the magnetic properties of superconductors, including the new high temperature superconductor materials, at the microscopic level. The technique directly measures the magnetic penetration depth (type II superconductors (SC's)) and detects the presence of magnetic ordering (antiferromagnetism or spin-glass ordering were observed in some high temperature superconductor (HTSC's) and in many closely related compounds). Extensive studies of HTSC materials were conducted by the Virginia State University - College of William and Mary - Columbia University collaboration at Brookhaven National Laboratory and TRIUMF (Vancouver). A survey of LaSrCuO and YBaCaCuO systems shows an essentially linear relationship between the transition temperature T(sub c) and the relaxation rate. This appears to be a manifestation of the proportionality between T(sub c) and the Fermi energy, which suggests a high energy scale for the SC coupling, and which is not consistent with the weak coupling of phonon-mediated SC. Studies of LaCuO and YBaCuO parent compounds show clear evidence of antiferromagnetism. YBa2Cu(3-x)CO(x)O7 shows the simultaneous presence of spin-glass magnetic ordering and superconductivity. Three-dimensional SC, (Ba, K) BiO3, unlike the layered CuO-based compounds, shows no suggestion of magnetic ordering. Experimental techniques and theoretical implications are discussed

Predictive significance of the six-minute walk distance for long-term survival in chronic hypercapnic respiratory failure

Background: The 6-min walk distance ( 6-MWD) is a global marker of functional capacity and prognosis in chronic obstructive pulmonary disease ( COPD), but less explored in other chronic respiratory diseases. Objective: To study the role of 6-MWD in chronic hypercapnic respiratory failure ( CHRF). Methods: In 424 stable patients with CHRF and non-invasive ventilation ( NIV) comprising COPD ( n = 197), restrictive diseases ( RD; n = 112) and obesity-hypoventilation- syndrome ( OHS; n = 115), the prognostic value of 6-MWD for long- term survival was assessed in relation to that of body mass index (BMI), lung function, respiratory muscle function and laboratory parameters. Results: 6-MWD was reduced in patients with COPD ( median 280 m; quartiles 204/350 m) and RD ( 290 m; 204/362 m) compared to OHS ( 360 m; 275/440 m; p <0.001 each). Overall mortality during 24.9 (13.1/40.5) months was 22.9%. In the 424 patients with CHRF, 6-MWD independently predicted mortality in addition to BMI, leukocytes and forced expiratory volume in 1 s ( p <0.05 each). In COPD, 6-MWD was strongly associated with mortality using the median {[} p <0.001, hazard ratio ( HR) = 3.75, 95% confidence interval (CI): 2.24-6.38] or quartiles as cutoff levels. In contrast, 6-MWD was only significantly associated with impaired survival in RD patients when it was reduced to 204 m or less (1st quartile; p = 0.003, HR = 3.31, 95% CI: 1.73-14.10), while in OHS 6-MWD had not any prognostic value. Conclusions: In patients with CHRF and NIV, 6-MWD was predictive for long- term survival particularly in COPD. In RD only severely reduced 6-MWD predicted mortality, while in OHS 6-MWD was relatively high and had no prognostic value. These results support a disease-specific use of 6-MWD in the routine assessment of patients with CHRF. Copyright (C) 2007 S. Karger AG, Basel

Paleontological records indicate the occurrence of open woodlands in a dry inland climate at the present-day Arctic coast in western Beringia during the Last Interglacial

Permafrost records, accessible at outcrops along the coast of Oyogos Yar at the Dmitry Laptev Strait, NE-Siberia, provide unique insights into the environmental history of Western Beringia during the Last Interglacial. The remains of terrestrial and freshwater organisms, including plants, coleopterans, chironomids, cladocerans, ostracods and molluscs, have been preserved in the frozen deposits of a shallow paleo-lake and indicate a boreal climate at the present-day arctic mainland coast during the Last Interglacial. Terrestrial beetle and plant remains suggest the former existence of open forest-tundra with larch (Larix dahurica), tree alder (Alnus incana), birch and alder shrubs (Duschekia fruticosa, Betula fruticosa, Betula divaricata, Betula nana), interspersed with patches of steppe and meadows. Consequently, the tree line was shifted to at least 270. km north of its current position. Aquatic organisms, such as chironomids, cladocerans, ostracods, molluscs and hydrophytes, indicate the formation of a shallow lake as the result of thermokarst processes. Steppe plants and beetles suggest low net precipitation. Littoral pioneer plants and chironomids indicate intense lake level fluctuations due to high evaporation. Many of the organisms are thermophilous, indicating a mean air temperature of the warmest month that was greater than 13 °C, which is above the minimum requirements for tree growth. These temperatures are in contrast to the modern values of less than 4 °C in the study area. The terrestrial and freshwater organism remains were found at a coastal exposure that was only 3.5. m above sea level and in a position where they should have been under sea during the Last Interglacial when the global sea level was 6-10. m higher than the current levels. The results suggest that during the last warm stage, the site was inland, and its modern coastal situation is the result of tectonic subsidence. © 2010 Elsevier Ltd

Thermodynamic properties of excess-oxygen-doped La2CuO4.11 near a simultaneous transition to superconductivity and long-range magnetic order

We have measured the specific heat and magnetization {\it versus} temperature in a single crystal sample of superconducting La$_{2}$CuO$_{4.11}$ and in a sample of the same material after removing the excess oxygen, in magnetic fields up to 15 T. Using the deoxygenated sample to subtract the phonon contribution, we find a broad peak in the specific heat, centered at 50 K. This excess specific heat is attributed to fluctuations of the Cu spins possibly enhanced by an interplay with the charge degrees of freedom, and appears to be independent of magnetic field, up to 15 T. Near the superconducting transition $T_{c}$($H$=0)= 43 K, we find a sharp feature that is strongly suppressed when the magnetic field is applied parallel to the crystallographic c-axis. A model for 3D vortex fluctuations is used to scale magnetization measured at several magnetic fields. When the magnetic field is applied perpendicular to the c-axis, the only observed effect is a slight shift in the superconducting transition temperature.Comment: 8 pages, 8 figure

Modelling neurofibromatosis type 1 tibial dysplasia and its treatment with lovastatin

<p>Abstract</p> <p>Background</p> <p>Bowing and/or pseudarthrosis of the tibia is a known severe complication of neurofibromatosis type 1 (NF1). Mice with conditionally inactivated neurofibromin (Nf1) in the developing limbs and cranium (Nf1Prx1) show bowing of the tibia caused by decreased bone mineralisation and increased bone vascularisation. However, in contrast to NF1 patients, spontaneous fractures do not occur in Nf1Prx1 mice probably due to the relatively low mechanical load. We studied bone healing in a cortical bone injury model in Nf1Prx1 mice as a model for NF1-associated bone disease. Taking advantage of this experimental model we explore effects of systemically applied lovastatin, a cholesterol-lowering drug, on the Nf1 deficient bone repair.</p> <p>Methods</p> <p>Cortical injury was induced bilaterally in the <it>tuberositas tibiae </it>in Nf1Prx1 mutant mice and littermate controls according to a method described previously. Paraffin as well as methacrylate sections were analysed from each animal. We divided 24 sex-matched mutant mice into a lovastatin-treated and an untreated group. The lovastatin-treated mice received 0.15 mg activated lovastatin by daily gavage. The bone repair process was analysed at three consecutive time points post injury, using histological methods, micro computed tomography measurements and <it>in situ </it>hybridisation. At each experimental time point, three lovastatin-treated mutant mice, three untreated mutant mice and three untreated control mice were analysed. The animal group humanely killed on day 14 post injury was expanded to six treated and six untreated mutant mice as well as six control mice.</p> <p>Results</p> <p>Bone injury repair is a complex process, which requires the concerted effort of numerous cell types. It is initiated by an inflammatory response, which stimulates fibroblasts from the surrounding connective tissue to proliferate and fill in the injury site with a provisional extracellular matrix. In parallel, mesenchymal progenitor cells from the periost are recruited into the injury site to become osteoblasts. In Nf1Prx1 mice bone repair is delayed and characterised by the excessive formation and the persistence of fibro-cartilaginous tissue and impaired extracellular matrix mineralisation. Correspondingly, expression of Runx2 is downregulated. High-dose systemic lovastatin treatment restores Runx2 expression and accelerates new bone formation, thus improving cortical bone repair in Nf1Prx1 tibia. The bone anabolic effects correlate with a reduction of the mitogen activated protein kinase pathway hyper-activation in Nf1-deficient cells.</p> <p>Conclusion</p> <p>Our data suggest the potential usefulness of lovastatin, a drug approved by the US Food and Drug Administration in 1987 for the treatment of hypercholesteraemia, in the treatment of Nf1-related fracture healing abnormalities. The experimental model presented here constitutes a valuable tool for the pre-clinical stage testing of candidate drugs, targeting Nf1-associated bone dysplasia.</p

Immune Response and Mitochondrial Metabolism Are Commonly Deregulated in DMD and Aging Skeletal Muscle

Duchenne Muscular Dystrophy (DMD) is a complex process involving multiple pathways downstream of the primary genetic insult leading to fatal muscle degeneration. Aging muscle is a multifactorial neuromuscular process characterized by impaired muscle regeneration leading to progressive atrophy. We hypothesized that these chronic atrophying situations may share specific myogenic adaptative responses at transcriptional level according to tissue remodeling. Muscle biopsies from four young DMD and four AGED subjects were referred to a group of seven muscle biopsies from young subjects without any neuromuscular disorder and explored through a dedicated expression microarray. We identified 528 differentially expressed genes (out of 2,745 analyzed), of which 328 could be validated by an exhaustive meta-analysis of public microarray datasets referring to DMD and Aging in skeletal muscle. Among the 328 validated co-expressed genes, 50% had the same expression profile in both groups and corresponded to immune/fibrosis responses and mitochondrial metabolism. Generalizing these observed meta-signatures with large compendia of public datasets reinforced our results as they could be also identified in other pathological processes and in diverse physiological conditions. Focusing on the common gene signatures in these two atrophying conditions, we observed enrichment in motifs for candidate transcription factors that may coordinate either the immune/fibrosis responses (ETS1, IRF1, NF1) or the mitochondrial metabolism (ESRRA). Deregulation in their expression could be responsible, at least in part, for the same transcriptome changes initiating the chronic muscle atrophy. This study suggests that distinct pathophysiological processes may share common gene responses and pathways related to specific transcription factors

Relations between excitability and contractility in rat soleus muscle: role of the Na+-K+ pump and Na+/K+ gradients

The effects of reduced Na+/K+ gradients and Na+-K+ pump stimulation on compound action potentials (M waves) and contractile force were examined in isolated rat soleus muscles stimulated through the nerve.Exposure of muscles to buffer containing 85 mM Na+ and 9 mM K+ (85 Na+/9 K+ buffer) produced a 54 % decrease in M wave area and a 50 % decrease in tetanic force compared with control levels in standard buffer containing 147 mM Na+ and 4 mM K+. Subsequent stimulation of active Na+-K+ transport, using the β2-adrenoceptor agonist salbutamol, induced a marked recovery of M wave area and tetanic force (to 98 and 87 % of the control level, respectively). Similarly, stimulation of active Na+-K+ transport with insulin induced a significant recovery of M wave area and tetanic force.During equilibration with 85 Na+/9 K+ buffer and after addition of salbutamol there was a close linear correlation between M wave area and tetanic force (r = 0·92, P< 0·001). Similar correlations were found in muscles where tetrodotoxin was used to reduce excitability and in muscles fatigued by 120 s of continuous stimulation at a frequency of 30 Hz.These results show a close correlation between excitability and tetanic force. Furthermore, in muscles depressed by a reduction in the Na+/K+ gradients, β-adrenergic stimulation of the Na+-K+ pump induces a recovery of excitability which can fully explain the previously demonstrated recovery of tetanic force following Na+-K+ pump stimulation. Moreover, the data indicate that loss of excitability is an important factor in fatigue induced by high-frequency (30 Hz) stimulation