Cyclophosphamide induces NR2B phosphorylation-dependent facilitation on spinal reflex potentiation

Chang CH, Peng HY, Wu HC, Lai CY, Hsieh MC, Lin TB. Cyclophosphamide induces NR2B phosphorylation-dependent facilitation on spinal reflex potentiation. Am J Physiol Renal Physiol 300: F692-F699, 2011. First published November 24, 2010; doi:10.1152/ajprenal.00531.2010.-It is well-established that cyclophosphamide (CYP) can sensitize the pelvic afferent nerve arising from the urinary bladder and therefore induce suprapubic pain. To test the possibility that CYP might mediate the development of visceral hypereflexia/hyperalgesia by facilitating spinal activity-dependent neural plasticity, we compared the pelvic-urethra reflex activity and spinal N-methyl-D-aspartate receptor NR2B subunit (NR2B) phosphorylation in rats treated with vehicle solution and CYP. Compared with vehicle solution, when accompanied by upregulation of phosphorylated NR2B expression in the lumbosacral (L6-S2) dorsal horn, CYP increased the evoked spikes in spinal reflex potentiation induced by repetitive stimulation (1 stimulation/1 s). Moreover, intraperitoneal pretreatments with N(G)-nitro-L-arginine methyl ester and roscovitine, nitric oxide synthase and cyclin-dependent protein kinase 5 (Cdk5) antagonists, respectively, overwrote CYP-enhanced reflex potentiation and NR2B phosphorylation. When compared with the untreated group, the treatment with small-interfering RNA of NR2B, which decreased the expression of NR2B expression, abolished CYP-dependent reflex facilitation and spinal NR2B phosphorylation. These results suggested that CYP might facilitate spinal reflex potentiation mediated by N-methyl-D-aspartate receptors and participate in the development of visceral hypereflexia/hyperalgesia through nitric oxide-and Cdk5-dependent NR2B phosphorylation at the lumbosacral dorsal horn

EphrinB2 induces pelvic-urethra reflex potentiation via Src kinase-dependent tyrosine phosphorylation of NR2B

Wu HC, Chang CH, Peng HY, Chen GD, Lai CY, Hsieh MC, Lin TB. EphrinB2 induces pelvic-urethra reflex potentiation via Src kinase-dependent tyrosine phosphorylation of NR2B. Am J Physiol Renal Physiol 300: F403-F411, 2011. First published December 8, 2010; doi:10.1152/ajprenal.00520.2010.-Recently, the role of EphB receptor (EphBR) tyrosine kinase and their ephrinB ligands in pain-related neural plasticity at the spinal cord level have been identified. To test whether Src-family tyrosine kinase-dependent glutamatergic N-methyl-D-aspartate receptor NR2B subunit phosphorylation underlies lumbosacral spinal EphBR activation to mediate pelvic-urethra reflex potentiation, we recorded external urethra sphincter electromyogram reflex activity and analyzed protein expression in the lumbosacral (L(6)-S(2)) dorsal horn in response to intrathecal ephrinB2 injections. When compared with vehicle solution, exogenous ephrinB2 (5 mu g/rat it)-induced reflex potentiation, in associated with phosphorylation of EphB1/2, Src-family kinase, NR2B Y1336 and Y1472 tyrosine residues. Both intrathecal EphB1 and EphB2 immunoglobulin fusion protein (both 10 mu g/rat it) prevented ephrinB2-dependent reflex potentiation, as well as protein phosphorylation. Pretreatment with PP2 (50 mu M, 10 mu l it), an Src-family kinase antagonist, reversed the reflex potentiation, as well as Src kinase and NR2B phosphorylation. Together, these results suggest the ephrinB2-dependent EphBR activation, which subsequently provokes Src kinase-mediated N-methyl-D-aspartate receptor NR2B phosphorylation in the lumbosacral dorsal horn, is crucial for the induction of spinal reflex potentiation contributing to the development of visceral pain and/or hyperalgesia in the pelvic area

The relative efficacy of different strain combinations of lactic acid bacteria in the reduction of populations of Salmonella enterica Typhimurium in the livers and spleens of mice

Multispecies probiotics have been reported to be more effective than monostrain probiotics in health promoting for the host. In this study, 12 lactic acid bacteria (LAB) strains were selected based on the level of induction of tumor necrosis factor (TNF)-alpha in RAW 264.7 macrophage cells. Their adherence to Caco-2 cells and inhibitory effects on Salmonella invasion of Caco-2 cells were compared. Strains with different probiotic properties were then combined and BALB/c mice were fed with LAB strains for 63 days; then the mice were challenged with Salmonella on day 64. For Salmonella-unchallenged mice that received a multistrain combination of LAB strains that have greater TNF-alpha production in macrophages, greater adherence and inhibit Salmonella invasion of Caco-2 cells to a greater extent, their peritoneal macrophages had greater phagocytic activity. For Salmonella-challenged mice, a significant reduction of Salmonella cells in the livers and spleens of the mice was observed 8 days post challenge. The addition of 12% skim milk powder together with LAB strain combinations significantly enhanced the reduction of Salmonella cells in the mice livers and spleens. In conclusion, we have shown that LAB strain combinations with particular probiotic properties when fed to mice can inhibit Salmonella invasion of the liver and spleen

MultiPath TCP: From Theory to Practice

Abstract. The IETF is developing a new transport layer solution, MultiPath TCP (MPTCP), which allows to efficiently exploit several Internet paths between a pair of hosts, while presenting a single TCP connection to the application layer. From an implementation viewpoint, multiplexing flows at the transport layer raises several challenges. We first explain how this major TCP extension affects the Linux TCP/IP stack when considering the establishment of TCP connections and the transmission and reception of data over multiple paths. Then, based on our implementation of MultiPath TCP in the Linux kernel, we explain how such an implementation can be optimized to achieve high performance and report measurements showing the performance of receive buffer tuning and coupled congestion control

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society

Periodicities in the Daily Proton Fluxes from 2011 to 2019 Measured by the Alpha Magnetic Spectrometer on the International Space Station from 1 to 100 GV

We present the precision measurement of the daily proton fluxes in cosmic rays from May 20, 2011 to October 29, 2019 (a total of 2824 days or 114 Bartels rotations) in the rigidity interval from 1 to 100 GV based on 5.5×109 protons collected with the Alpha Magnetic Spectrometer aboard the International Space Station. The proton fluxes exhibit variations on multiple timescales. From 2014 to 2018, we observed recurrent flux variations with a period of 27 days. Shorter periods of 9 days and 13.5 days are observed in 2016. The strength of all three periodicities changes with time and rigidity. The rigidity dependence of the 27-day periodicity is different from the rigidity dependences of 9-day and 13.5-day periods. Unexpectedly, the strength of 9-day and 13.5-day periodicities increases with increasing rigidities up to ∼10 GV and ∼20 GV, respectively. Then the strength of the periodicities decreases with increasing rigidity up to 100 GV.</p

Precision Measurement of the Proton Flux in Primary Cosmic Rays from Rigidity 1 GV to 1.8 TV with the Alpha Magnetic Spectrometer on the International Space Station

A precise measurement of the proton flux in primary cosmic rays with rigidity (momentum/charge) from 1 GV to 1.8 TV is presented based on 300 million events. Knowledge of the rigidity dependence of the proton flux is important in understanding the origin, acceleration, and propagation of cosmic rays. We present the detailed variation with rigidity of the flux spectral index for the first time. The spectral index progressively hardens at high rigidities.</p

Search for gravitational-wave transients associated with magnetar bursts in advanced LIGO and advanced Virgo data from the third observing run

Gravitational waves are expected to be produced from neutron star oscillations associated with magnetar giant f lares and short bursts. We present the results of a search for short-duration (milliseconds to seconds) and longduration (∼100 s) transient gravitational waves from 13 magnetar short bursts observed during Advanced LIGO, Advanced Virgo, and KAGRA’s third observation run. These 13 bursts come from two magnetars, SGR1935 +2154 and SwiftJ1818.0−1607. We also include three other electromagnetic burst events detected by FermiGBM which were identified as likely coming from one or more magnetars, but they have no association with a known magnetar. No magnetar giant flares were detected during the analysis period. We find no evidence of gravitational waves associated with any of these 16 bursts. We place upper limits on the rms of the integrated incident gravitational-wave strain that reach 3.6 × 10−²³ Hz at 100 Hz for the short-duration search and 1.1 ×10−²² Hz at 450 Hz for the long-duration search. For a ringdown signal at 1590 Hz targeted by the short-duration search the limit is set to 2.3 × 10−²² Hz. Using the estimated distance to each magnetar, we derive upper limits upper limits on the emitted gravitational-wave energy of 1.5 × 1044 erg (1.0 × 1044 erg) for SGR 1935+2154 and 9.4 × 10^43 erg (1.3 × 1044 erg) for Swift J1818.0−1607, for the short-duration (long-duration) search. Assuming isotropic emission of electromagnetic radiation of the burst fluences, we constrain the ratio of gravitational-wave energy to electromagnetic energy for bursts from SGR 1935+2154 with the available fluence information. The lowest of these ratios is 4.5 × 103