Meningeal mast cells as key effectors of stroke pathology

Stroke is the leading cause of adult disability in the United States. Because post-stroke inflammation is a critical determinant of damage and recovery after stroke, understanding the interplay between the immune system and the brain after stroke holds much promise for therapeutic intervention. An understudied, but important aspect of this interplay is the role of meninges that surround the brain. All blood vessels travel through the meningeal space before entering the brain parenchyma, making the meninges ideally located to act as an immune gatekeeper for the underlying parenchyma. Emerging evidence suggests that the actions of immune cells resident in the meninges are essential for executing this gatekeeper function. Mast cells (MCs), best known as pro-inflammatory effector cells, are one of the long-term resident immune cells in the meninges. Here, we discuss recent findings in the literature regarding the role of MCs located in the meningeal space and stroke pathology. We review the latest advances in mouse models to investigate the roles of MCs and MC-derived products in vivo, and the importance of using these mouse models. We examine the concept of the meninges playing a critical role in brain and immune interactions, re-evaluate the perspectives on the key effectors of stroke pathology, and discuss the opportunities and challenges for therapeutic development.Ahmet Arac, Michele A. Grimbaldeston, Stephen J. Galli, Tonya M. Bliss and Gary K. Steinber

Spin interactions of interstitial Mn ions in ferromagnetic GaMnAs

The recently reported Rutherford backscattering and particle-induced X-ray emission experiments have revealed that in low-temperature MBE grown GaMnAs a significant part of the incorporated Mn atoms occupies tetrahedral interstitial sites in the lattice. Here we study the magnetic properties of these interstitial ions. We show that they do not participate in the hole-induced ferromagnetism. Moreover, Mn interstitial double donors may form pairs with the nearest substitutional Mn acceptors - our calculations evidence that the spins in such pairs are antiferromagnetically coupled by the superexchange. We also show that for the Mn ion in the other, hexagonal, interstitial position (which seems to be the case in the GaMnBeAs samples) the p-d interactions with the holes, responsible for the ferromagnetism, are very much suppressed.Comment: 4 pages, 3 figures, submitted to PR

Why Are People's Decisions Sometimes Worse with Computer Support?

In many applications of computerised decision support, a recognised source of undesired outcomes is operators' apparent over-reliance on automation. For instance, an operator may fail to react to a potentially dangerous situation because a computer fails to generate an alarm. However, the very use of terms like "over-reliance" betrays possible misunderstandings of these phenomena and their causes, which may lead to ineffective corrective action (e.g. training or procedures that do not counteract all the causes of the apparently "over-reliant" behaviour). We review relevant literature in the area of "automation bias" and describe the diverse mechanisms that may be involved in human errors when using computer support. We discuss these mechanisms, with reference to errors of omission when using "alerting systems", with the help of examples of novel counterintuitive findings we obtained from a case study in a health care application, as well as other examples from the literature

Study of the B^0 Semileptonic Decay Spectrum at the Upsilon(4S) Resonance

We have made a first measurement of the lepton momentum spectrum in a sample of events enriched in neutral B's through a partial reconstruction of B0 --> D*- l+ nu. This spectrum, measured with 2.38 fb**-1 of data collected at the Upsilon(4S) resonance by the CLEO II detector, is compared directly to the inclusive lepton spectrum from all Upsilon(4S) events in the same data set. These two spectra are consistent with having the same shape above 1.5 GeV/c. From the two spectra and two other CLEO measurements, we obtain the B0 and B+ semileptonic branching fractions, b0 and b+, their ratio, and the production ratio f+-/f00 of B+ and B0 pairs at the Upsilon(4S). We report b+/b0=0.950 (+0.117-0.080) +- 0.091, b0 = (10.78 +- 0.60 +- 0.69)%, and b+ = (10.25 +- 0.57 +- 0.65)%. b+/b0 is equivalent to the ratio of charged to neutral B lifetimes, tau+/tau0.Comment: 14 page, postscript file also available at http://w4.lns.cornell.edu/public/CLN

Radiative Decay Modes of the D0D^{0} Meson

Using data recorded by the CLEO-II detector at CESR we have searched for four radiative decay modes of the $D^0$ meson: $D^0\to\phi\gamma$, $D^0\to\omega\gamma$, $D^0\to\bar{K}^{*}\gamma$, and $D^0\to\rho^0\gamma$. We obtain 90% CL upper limits on the branching ratios of these modes of $1.9\times 10^{-4}$, $2.4\times 10^{-4}$, $7.6\times 10^{-4}$ and $2.4\times 10^{-4}$ respectively.Comment: 15 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Measurement of the Mass Splittings between the bbˉχb,J(1P)b\bar{b}\chi_{b,J}(1P) States

We present new measurements of photon energies and branching fractions for the radiative transitions: Upsilon(2S)->gamma+chi_b(J=0,1,2). The masses of the chi_b states are determined from the measured radiative photon energies. The ratio of mass splittings between the chi_b substates, r==(M[J=2]-M[J=1])/(M[J=1]-M[J=0]) with M the chi_b mass, provides information on the nature of the bbbar confining potential. We find r(1P)=0.54+/-0.02+/-0.02. This value is in conflict with the previous world average, but more consistent with the theoretical expectation that r(1P)<r(2P); i.e., that this mass splittings ratio is smaller for the chi_b(1P) triplet than for the chi_b(2P) triplet.Comment: 11 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

A monovalent chimpanzee adenovirus Ebola vaccine boosted with MVA

BACKGROUND The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. The development of an effective Ebola vaccine is a priority for control of a future outbreak. METHODS In this phase 1 study, we administered a single dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) to 60 healthy adult volunteers in Oxford, United Kingdom. The vaccine was administered in three dose levels — 1×1010 viral particles, 2.5×1010 viral particles, and 5×1010 viral particles — with 20 participants in each group. We then assessed the effect of adding a booster dose of a modified vaccinia Ankara (MVA) strain, encoding the same Ebola virus glyco- protein, in 30 of the 60 participants and evaluated a reduced prime–boost interval in another 16 participants. We also compared antibody responses to inactivated whole Ebola virus virions and neutralizing antibody activity with those observed in phase 1 studies of a recombinant vesicular stomatitis virus–based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) to determine relative potency and assess durability. RESULTS No safety concerns were identified at any of the dose levels studied. Four weeks after immunization with the ChAd3 vaccine, ZEBOV-specific antibody responses were similar to those induced by rVSV-ZEBOV vaccination, with a geometric mean titer of 752 and 921, respectively. ZEBOV neutralization activity was also similar with the two vaccines (geo- metric mean titer, 14.9 and 22.2, respectively). Boosting with the MVA vector increased virus-specific antibodies by a factor of 12 (geometric mean titer, 9007) and increased glycoprotein-specific CD8+ T cells by a factor of 5. Significant increases in neutralizing antibodies were seen after boosting in all 30 participants (geometric mean titer, 139; P<0.001). Virus-specific antibody responses in participants primed with ChAd3 remained positive 6 months after vaccination (geometric mean titer, 758) but were significantly higher in those who had received the MVA booster (geometric mean titer, 1750; P<0.001). CONCLUSIONS The ChAd3 vaccine boosted with MVA elicited B-cell and T-cell immune responses to ZEBOV that were superior to those induced by the ChAd3 vaccine alone. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT02240875.

Studies of the Cabbibo-Suppressed Decays D+→π0ℓ+νD^+ \to \pi^0 \ell^+ \nu and D+→ηe+νeD^+ \to \eta e^+ \nu_e

Using 4.8 fb$^{-1}$ of data taken with the CLEO II detector, the branching fraction for the Cabibbo-suppressed decay $D^+\to\pi^0\ell^+\nu$ measured relative to the Cabibbo favored decay $D^+\to\bar{K^0}\ell^+\nu$ is found to be $0.046\pm 0.014\pm 0.017$. Using $V_{cs}$ and $V_{cd}$ from unitarity constraints, we determine $| f_+^{\pi}(0)/f_+^K(0)|^2=0.9\pm 0.3\pm 0.3$ We also present a 90% confidence level upper limit for the branching ratio of the decay $D^+ \to \eta e^+\nu_e$ relative to that for $D^+ \to \pi^0 e^+\nu_e$ of 1.5.Comment: 10 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN