Two forms of short-interval intracortical inhibition in human motor cortex

Background: Pulses of transcranial magnetic stimulation (TMS) with a predominantly anterior-posterior (AP) or posterior-anterior (PA) current direction over the primary motor cortex appear to activate distinct excitatory inputs to corticospinal neurons. In contrast, very few reports have examined whether the inhibitory neurons responsible for short-interval intracortical inhibition (SICI) are sensitive to TMS current direction. Objectives: To investigate whether SICI evaluated with AP and PA conditioning stimuli (CSPA and CSAP) activate different inhibitory pathways. SICI was always assessed using a PA-oriented test stimulus (TSPA). Methods: Using two superimposed TMS coils, CSPA and CSAP were applied at interstimulus intervals (ISI) of 1–5 ms before a TSPA, and at a range of different intensities. Using a triple stimulation design, we then tested whether SICI at ISI of 3 ms using opposite directions of CS (SICICSPA3 and SICICSAP3) interacted differently with three other forms of inhibition, including SICI at ISI of 2 ms (SICICSPA2), cerebellum-motor cortex inhibition (CBI 5 ms) and short-latency afferent inhibition (SAI 22 ms). Finally, we compared the effect of tonic and phasic voluntary contraction on SICICSPA3 and SICICSAP3. Results: CSAP produced little SICI at ISIs = 1 and 2 ms. However, at ISI = 3 ms, both CSAP and CSPA were equally effective at the same percent of maximum stimulator output. Despite this apparent similarity, combining SICICSPA3 or SICICSAP3 with other forms of inhibition led to quite different results: SICICSPA3 interacted in complex ways with CBI, SAI and SICICSPA2, whereas the effect of SICICSAP3 appeared to be quite independent of them. Although SICICSPA and SICICSAP were both reduced by the same amount during voluntary tonic contraction compared with rest, in a simple reaction time task SICICSAP was disinhibited much earlier following the imperative signal than SICICSPA. Conclusions: SICICSPA appears to activate a different inhibitory pathway to that activated by SICICSAP. The difference is behaviourally relevant since the pathways are controlled differently during volitional contraction. The results may explain some previous pathological data and open the possibility of testing whether these pathways are differentially recruited in a range of tasks

Kaon Production and Interaction

Exclusive data on both the elementary kaon and antikaon production channels have been taken at the cooler synchrotron COSY in proton-proton scattering. In the kaon--hyperon production an enhancement by one order of magnitude of the Lambda/Sigma0 ratio has been observed at excess energies below Q=13 MeV compared to data at higher excess energies (Q>300 MeV). New results obtained at the COSY-11 facility explore the transition region between the regime of this low-energy Sigma0 suppression and excess energies of 60 MeV. A comparison of the energy dependence of the Lambda and Sigma0 total cross sections exhibits distinct qualitative differences between both hyperon production channels. Studies of kaon-antikaon production have been motivated especially by the ongoing discussion about the nature of the scalar resonances f0(980) and a0(980) coupling to the K anti-K channel. For the reaction pp->ppK+K- a first total cross section value is reported at an excess energy of Q=17 MeV, i.e. below the phi threshold. Calculations obtained within an OBE model indicate that the energy dependence of the available total cross section data close to threshold is rather difficult to reconcile with the assumption of a phase-space behaviour modified predominantly by the proton-proton final state interaction.Comment: 10 pages, 4 figures, Presented at Meson 2002: 7th International Workshop on Meson Production, Properties and Interaction, Cracow, Poland, 24-28 May 200

The DArk Matter Particle Explorer mission

The DArk Matter Particle Explorer (DAMPE), one of the four scientific space science missions within the framework of the Strategic Pioneer Program on Space Science of the Chinese Academy of Sciences, is a general purpose high energy cosmic-ray and gamma-ray observatory, which was successfully launched on December 17th, 2015 from the Jiuquan Satellite Launch Center. The DAMPE scientific objectives include the study of galactic cosmic rays up to $\sim 10$ TeV and hundreds of TeV for electrons/gammas and nuclei respectively, and the search for dark matter signatures in their spectra. In this paper we illustrate the layout of the DAMPE instrument, and discuss the results of beam tests and calibrations performed on ground. Finally we present the expected performance in space and give an overview of the mission key scientific goals.Comment: 45 pages, including 29 figures and 6 tables. Published in Astropart. Phy

An Experimentalist's View of Neutrino Oscillations

Neutrinos, and primarily neutrino oscillations, have undoubtedly been one of the most exciting topics in the field of high-energy physics over the past few years. The existence of neutrino oscillations would require an extension of the currently accepted description of sub-nuclear phenomena beyond the Standard Model. Compelling evidence of new physics, which seems to be pointing towards neutrino oscillations, is coming from the solar neutrino deficit and from the atmospheric neutrino anomaly. More controversial effects have been observed with artificially produced neutrinos. The present experimental status of neutrino oscillations is reviewed, as well as the planned future experimental programme, which, it is hoped, will solve most of the outstanding puzzles.Comment: 64 pages, 29 figures, to be published in Intern. J. Mod. Phys. A (2001

Direct detection of a break in the teraelectronvolt cosmic-ray spectrum of electrons and positrons

High energy cosmic ray electrons plus positrons (CREs), which lose energy quickly during their propagation, provide an ideal probe of Galactic high-energy processes and may enable the observation of phenomena such as dark-matter particle annihilation or decay. The CRE spectrum has been directly measured up to $\sim 2$ TeV in previous balloon- or space-borne experiments, and indirectly up to $\sim 5$ TeV by ground-based Cherenkov $\gamma$-ray telescope arrays. Evidence for a spectral break in the TeV energy range has been provided by indirect measurements of H.E.S.S., although the results were qualified by sizeable systematic uncertainties. Here we report a direct measurement of CREs in the energy range $25~{\rm GeV}-4.6~{\rm TeV}$ by the DArk Matter Particle Explorer (DAMPE) with unprecedentedly high energy resolution and low background. The majority of the spectrum can be properly fitted by a smoothly broken power-law model rather than a single power-law model. The direct detection of a spectral break at $E \sim0.9$ TeV confirms the evidence found by H.E.S.S., clarifies the behavior of the CRE spectrum at energies above 1 TeV and sheds light on the physical origin of the sub-TeV CREs.Comment: 18 pages, 6 figures, Nature in press, doi:10.1038/nature2447

Electro-chemical deposition of zinc oxide nanostructures by using two electrodes

One of the most viable ways to grow nanostructures is electro deposition. However, most electrodeposited samples are obtained by three-electrode electrochemical cell. We successfully use a much simpler two-electrode cell to grow different ZnO nanostructures from common chemical reagents. Concentration, pH of the electrolytes and growth parameters like potentials at the electrodes, are tailored to allow fast growth without complexity. Morphology and surface roughness are investigated by Scanning Electron and Air Force Microscopy (SEM and AFM) respectively, crystal structure by X-Ray Diffraction measurements (XRD) and ZnO stoichiometry by core level photoemission spectroscopy (XPS)

The 2009 outburst of H~1743-322 as observed by RXTE

We analyze the RXTE observations of the 2009 outburst of H~1743-322, as well as the observations of the previous five outbursts for comparison. The hardness-intensity diagram (HID) shows a complete counter-clockwise q-track for the 2009 outburst and, interestingly, the track falls in} between a huge one in 2003, with a complete transition to high/soft state, and that of} the failed outburst in 2008. It leaves the low/hard state but does not reach the leftmost edge of the overall HID. While the lowest hardness (6--19 keV/3--6 keV) values} in the HID is about 0.3--0.4 for the 2009 outburst, similar to the ``failed state transition" seen in the persistent black hole XRB Cyg X-1, the timing analysis shows that a transition to the high soft state occurred. During the low/hard state of the 2009 outburst, the inner radius of the accretion disk is found to be closer to the central black hole and have an anti-correlation with the disk temperature. These results may be understood as the reprocessing} of the hot corona on the disk's} soft X-rays, which can lead to an underestimation of the inner radius of the accretion disk. In the luminosity diagram of the corona versus the disk, the tracks of the outbursts} in 2003 and 2009 cross the line which represents a roughly equal contribution to the entire emission from the thermal and the non-thermal components;} the track of the 2008 outburst has the turn-over falling} on this line. This may be indicative of an emission balance between the corona and the disk, which prevents the state transition from going further than the low/hard state.Comment: accepted by A&

Free energy barrier for melittin reorientation from a membrane-bound state to a transmembrane state

An important step in a phospholipid membrane pore formation by melittin antimicrobial peptide is a reorientation of the peptide from a surface into a transmembrane conformation. In this work we perform umbrella sampling simulations to calculate the potential of mean force (PMF) for the reorientation of melittin from a surface-bound state to a transmembrane state and provide a molecular level insight into understanding peptide and lipid properties that influence the existence of the free energy barrier. The PMFs were calculated for a peptide to lipid (P/L) ratio of 1/128 and 4/128. We observe that the free energy barrier is reduced when the P/L ratio increased. In addition, we study the cooperative effect; specifically we investigate if the barrier is smaller for a second melittin reorientation, given that another neighboring melittin was already in the transmembrane state. We observe that indeed the barrier of the PMF curve is reduced in this case, thus confirming the presence of a cooperative effect

Photon Production from a Quark--Gluon Plasma

In-medium interactions of a particle in a hot plasma are considered in the framework of thermal field theory. The formalism to calculate gauge invariant rates for photon and dilepton production from the medium is given. In the application to a QED plasma, astrophysical consequences are pointed out. The photon production rate from strongly interacting quarks in the quark--gluon plasma, which might be formed in ultrarelativistic heavy ion collisions, is calculated in the previously unaccessible regime of photon energies of the order of the plasma temperature. For temperatures below the chiral phase transition, an effective field theory incorporating dynamical chiral symmetry breaking is employed, and perturbative QCD at higher temperatures. A smooth transition between both regions is obtained. The relevance to the soft photon problem and to high energy heavy ion experiments is discussed.Comment: Paper in ReVTeX. Figures and complete paper available via anonymous ftp, ftp://tpri6c.gsi.de/pub/phenning/hq95ga

AT7519, a Novel Small Molecule Multi-Cyclin Dependent Kinase Inhibitor, Induces Apoptosis in Multiple Myeloma VIA GSK3 beta

Dysregulated cell cycling is a universal hallmark of cancer and is often mediated by abnormal activation of cyclin-dependent kinases (CDKs) and their cyclin partners. Overexpression of individual complexes are reported in multiple myeloma (MM), making them attractive therapeutic targets. In this study, we investigate the preclinical activity of a novel small-molecule multi-CDK inhibitor, AT7519, in MM. We show the anti-MM activity of AT7519 displaying potent cytotoxicity and apoptosis; associated with in vivo tumor growth inhibition and prolonged survival. At the molecular level, AT7519 inhibited RNA polymerase II (RNA pol II) phosphorylation, a CDK9, 7 substrate, associated with decreased RNA synthesis confirmed by [(3)H] Uridine incorporation. In addition, AT7519 inhibited glycogen synthase kinase 3beta (GSK-3beta) phosphorylation; conversely pretreatment with a selective GSK-3 inhibitor and shRNA GSK-3beta knockdown restored MM survival, suggesting the involvement of GSK-3beta in AT7519-induced apoptosis. GSK-3beta activation was independent of RNA pol II dephosphorylation confirmed by alpha-amanitin, a specific RNA pol II inihibitor, showing potent inhibition of RNA pol II phosphorylation without corresponding effects on GSK-3beta phosphorylation. These results offer new insights into the crucial, yet controversial role of GSK-3beta in MM and show significant anti-MM activity of AT7519, providing the rationale for its clinical evaluation in MM