Numerical Analysis of Ca2+ Depletion in the Transverse Tubular System of Mammalian Muscle

AbstractCalcium currents were recorded in contracting and actively shortening mammalian muscle fibers. In order to characterize the influence of extracellular calcium concentration changes in the small unstirred lumina of the transverse tubular system (TTS) on the time course of the slow L-type calcium current (ICa), we have combined experimental measurements of ICa with quantitative numerical simulations of Ca2+ depletion. ICa was recorded both in calcium-buffered and unbuffered external solutions using the two-microelectrode voltage clamp technique (2-MVC) on short murine toe muscle fibers. A simulation program based on a distributed TTS model was used to calculate the effect of ion depletion in the TTS. The experimental data obtained in a solution where ion depletion is suppressed by a high amount of a calcium buffering agent were used as input data for the simulation. The simulation output was then compared with experimental data from the same fiber obtained in unbuffered solution. Taking this approach, we could quantitatively show that the calculated Ca2+ depletion in the transverse tubular system of contracting mammalian muscle fibers significantly affects the time-dependent decline of Ca2+ currents. From our findings, we conclude that ion depletion in the tubular system may be one of the major effects for the ICa decline measured in isotonic physiological solution under voltage clamp conditions

Outbreak of encephalitic listeriosis in red-legged partridges (Alectoris rufa)

An outbreak of neurological disease was investigated in red-legged partridges between 8 and 28 days of age. Clinical signs included torticollis, head tilt and incoordination and over an initial eight day period approximately 30–40 fatalities occurred per day. No significant gross post mortem findings were detected. Histopathological examination of the brain and bacterial cultures followed by partial sequencing confirmed a diagnosis of encephalitis due to Listeria monocytogenes. Further isolates were obtained from follow-up carcasses, environmental samples and pooled tissue samples of newly imported day-old chicks prior to placement on farm. These isolates had the same antibiotic resistance pattern as the isolate of the initial post mortem submission and belonged to the same fluorescent amplified fragment length polymorphism (fAFLP) subtype. This suggested that the isolates were very closely related or identical and that the pathogen had entered the farm with the imported day-old chicks, resulting in disease manifestation in partridges between 8 and 28 days of age. Reports of outbreaks of encephalitic listeriosis in avian species are rare and this is to the best of our knowledge the first reported outbreak in red-legged partridges

Streptococcus pneumoniae exposure is associated with human metapneumovirus seroconversion and increased susceptibility to in vitro HMPV infection

AbstractIt remains largely unknown which factors determine the clinical outcome of human metapneumovirus (HMPV) infections. The aim of the present study was to analyse whether exposure to bacterial pathogens can influence HMPV infections. From 57 children, serum samples and colonization data for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pneumoniae were collected at 1.5, 6, 14 and 24 months of age. Seroconversion rates to HMPV were determined and related to bacterial carriage. Frequent nasopharyngeal carriage (≥2 times in the first 2 years of life) of S. pneumoniae, but not of the other three pathogens, was associated with increased seroconversion rates of infants to HMPV at the age of 2 years (frequently vs. less exposed, 93% vs. 59%; p <0.05). Subsequently, the susceptibility of well-differentiated normal human bronchial epithelial cells (wd-NHBE) pre-incubated with bacterial pathogens to in vitro HMPV infection was evaluated. Pre-incubation of wd-NHBE with S. pneumoniae resulted in increased susceptibility to infection with HMPV-enhanced green fluorescent protein (EGFP), as determined by enumeration of EGFP-positive cells. This was not the case for cells pre-incubated with H. influenzae, M. catarrhalis on S. aureus. We conclude that exposure to S. pneumoniae can modulate HMPV infection

Can a supernova be located by its neutrinos?

A future core-collapse supernova in our Galaxy will be detected by several neutrino detectors around the world. The neutrinos escape from the supernova core over several seconds from the time of collapse, unlike the electromagnetic radiation, emitted from the envelope, which is delayed by a time of order hours. In addition, the electromagnetic radiation can be obscured by dust in the intervening interstellar space. The question therefore arises whether a supernova can be located by its neutrinos alone. The early warning of a supernova and its location might allow greatly improved astronomical observations. The theme of the present work is a careful and realistic assessment of this question, taking into account the statistical significance of the various neutrino signals. Not surprisingly, neutrino-electron forward scattering leads to a good determination of the supernova direction, even in the presence of the large and nearly isotropic background from other reactions. Even with the most pessimistic background assumptions, SuperKamiokande (SK) and the Sudbury Neutrino Observatory (SNO) can restrict the supernova direction to be within circles of radius $5^\circ$ and $20^\circ$, respectively. Other reactions with more events but weaker angular dependence are much less useful for locating the supernova. Finally, there is the oft-discussed possibility of triangulation, i.e., determination of the supernova direction based on an arrival time delay between different detectors. Given the expected statistics we show that, contrary to previous estimates, this technique does not allow a good determination of the supernova direction.Comment: 11 pages including 2 figures. Revised version corrects typos, adds some brief comment

Induction of antibodies by Staphylococcus aureus nasal colonization in young children

AbstractIn order to develop novel antlstaphylococcal strategies, understanding the determinants of carriage and how humans respond to Staphylococcus aureus exposure is essential. Here, the primary S. aureus-specific humoral immune response and its association with nasal colonization was studied in young children. Sera from 57 colonized or non-colonized children, serially collected at birth and at 6, 14 and 24 months, were analysed for IgG, IgA and IgM binding to 19 staphylococcal proteins, using flow cytometry-based technology. The antibody responses showed extensive inter-individual variability. On average, the levels of antistaphylococcal IgA and IgM increased from birth until the age of 2 years (p <0.05), whereas the levels of IgG decreased (p <0.001). Placentally transferred maternal IgG did not protect against colonization. In colonized children, IgG and IgA levels for a number of proteins were higher than in non-colonized children. At both 14 and 24 months, the levels of IgG against chemotaxis inhibitory protein of S. aureus (at 24 months; median fluorescence intensity, 4928 vs. 24, p <0.05), extracellular fibrinogen-binding protein (987 vs. 604, p <0.05), and iron-responsive surface determinant H (62 vs. 5, p <0.05) were significantly higher in colonized children. The levels of IgA against CHIPS, IsdH and IsdA were higher (p <0.05). Therefore, CHIPS, Efb, IsdA and IsdH seem to play a role in nasal colonization of young children

Anti-staphylococcal humoral immune response in persistent nasal carriers and noncarriers of Staphylococcus aureus

BACKGROUND. Persistent carriers have a higher risk of Staphylococcus aureus infections than noncarriers but a lower risk of bacteremia-related death. Here, the role played by anti-staphylococcal antibodies was studied. METHODS. Serum samples from 15 persistent carriers and 19 noncarriers were analyzed for immunoglobulin (Ig) G, IgA, and IgM binding to 19 S. aureus antigens, by means of Luminex technology. Nasal secretions and serum samples obtained after 6 months were also analyzed. RESULTS. Median serum IgG levels were significantly higher in persistent carriers than in noncarriers for toxic shock syndrome toxin (TSST)-1 (median fluorescence intensity [MFI] value, 11,554 vs. 4291; P < .001) and staphylococcal enterotoxin (SE) A (742 vs. 218; P < .05); median IgA levels were higher for TSST-1 (P < .01), SEA, and clumping factor (Clf) A and B (P < .05). The in vitro neutralizing capacity of anti-TSST-1 antibodies was correlated with the MFI value (R(2) = 0.93) and was higher in persistent carriers (90.6% vs. 70.6%; P < .05). Antibody levels were stable over time and correlated with levels in nasal secretions (for IgG, R(2) = 0.87; for IgA, R(2) = 0.77). CONCLUSIONS. Antibodies to TSST-1 ha

CUORE: A Cryogenic Underground Observatory for Rare Events

CUORE is a proposed tightly packed array of 1000 TeO2 bolometers, each being a cube 5 cm on a side with a mass of 760 g. The array consists of 25 vertical towers, arranged in a square of 5 towers by 5 towers, each containing 10 layers of 4 crystals. The design of the detector is optimized for ultralow-background searches: for neutrinoless double beta decay of 130Te (33.8% abundance), cold dark matter, solar axions, and rare nuclear decays. A preliminary experiment involving 20 crystals 3x3x6 cm3 of 340 g has been completed, and a single CUORE tower is being constructed as a smaller scale experiment called CUORICINO. The expected performance and sensitivity, based on Monte Carlo simulations and extrapolations of present results, are reported.Comment: 39 pages, 12 figures, submitted to NI

Towards Practical Runtime Verification and Validation of Self-Adaptive Software Systems

International audienceSoftware validation and verification (V&V) ensures that software products satisfy user requirements and meet their expected quality attributes throughout their lifecycle. While high levels of adaptation and autonomy provide new ways for software systems to operate in highly dynamic environments, developing certifiable V&V methods for guaranteeing the achievement of self-adaptive software goals is one of the major challenges facing the entire research field. In this chapter we (i) analyze fundamental challenges and concerns for the development of V&V methods and techniques that provide certifiable trust in self-adaptive and self-managing systems; and (ii) present a proposal for including V&V operations explicitly in feedback loops for ensuring the achievement of software self-adaptation goals. Both of these contributions provide valuable starting points for V&V researchers to help advance this field

Influence of a classical homogeneous gravitational field on dissipative dynamics of the Jaynes-Cummings model with phase damping

In this paper, we study the dissipative dynamics of the Jaynes-Cummings model with phase damping in the presence of a classical homogeneous gravitational field. The model consists of a moving two-level atom simultaneously exposed to the gravitational field and a single-mode traveling radiation field in the presence of the phase damping. We present a quantum treatment of the internal and external dynamics of the atom based on an alternative su(2) dynamical algebraic structure. By making use of the super-operator technique, we obtain the solution of the master equation for the density operator of the quantum system, under the Markovian approximation. Assuming that initially the radiation field is prepared in a Glauber coherent state and the two-level atom is in the excited state, we investigate the influence of gravity on the temporal evolution of collapses and revivals of the atomic population inversion, atomic dipole squeezing, atomic momentum diffusion, photon counting statistics and quadrature squeezing of the radiation field in the presence of phase damping.Comment: 25 pages, 15 figure

Immunogenicity of toxins during Staphylococcus aureus infection

AB - BACKGROUND: Toxins are important Staphylococcus aureus virulence factors, but little is known about their immunogenicity during infection. Here, additional insight is generated. METHODS: Serum samples from 206 S. aureus-infected patients and 201 hospital-admitted control subjects were analyzed for immunoglobulin (Ig) G binding to 20 toxins, using flow-cytometry based technology. Antibody levels were associated with p