Delineating Astrocytic Cytokine Responses in a Human Stem Cell Model of Neural Trauma

Neuroinflammation has been shown to mediate the pathophysiological response following traumatic brain injury (TBI). Accumulating evidence implicates astrocytes as key immune cells within the central nervous system (CNS), displaying both pro- and anti-inflammatory properties. The aim of this study was to investigate how in vitro human astrocyte cultures respond to cytokines across a concentration range that approximates the aftermath of human TBI. To this end, enriched cultures of human induced pluripotent stem cell (iPSC)-derived astrocytes were exposed to interleukin-1β (IL-1β) (1–10,000 pg/mL), IL-4 (1–10,000 pg/mL), IL-6 (100–1,000,000 pg/mL), IL-10 (1–10,000 pg/mL) and tumor necrosis factor (TNF)-α (1–10,000 pg/mL). After 1, 24, 48 and 72 h, cultures were fixed and immunolabeled, and the secretome/supernatant was analyzed at 24, 48, and 72 h using a human cytokine/chemokine 39-plex Luminex assay. Data were compared to previous in vitro studies of neuronal cultures and clinical TBI studies. The secretome revealed concentration-, time- and/or both concentration- and time-dependent production of downstream cytokines (29, 21, and 17 cytokines, respectively, p<0.05). IL-1β exposure generated the most profound downstream response (27 cytokines), IL-6 and TNF had intermediate responses (13 and 11 cytokines, respectively), whereas IL-4 and IL-10 only led to weak responses over time or in escalating concentration (8 and 8 cytokines, respectively). Notably, expression of IL-1β, IL-6, and TNF cytokine receptor mRNA was higher in astrocyte cultures than in neuronal cultures. Several secreted cytokines had temporal trajectories, which corresponded to those seen in the aftermath of human TBI. In summary, iPSC-derived astrocyte cultures exposed to cytokine concentrations reflecting those in TBI generated an increased downstream cytokine production, particularly IL-1β. Although more work is needed to better understand how different cells in the CNS respond to the neuroinflammatory milieu after TBI, our data shows that iPSC-derived astrocytes represent a tractable model to study cytokine stimulation in a cell type-specific manner

Blocking representation in the ERA-Interim driven EURO-CORDEX RCMs

While Regional Climate Models (RCMs) have been shown to yield improved simulations compared to General Circulation Model (GCM), their representation of large-scale phenomena like atmospheric blocking has been hardly addressed. Here, we evaluate the ability of RCMs to simulate blocking situations present in their reanalysis driving data and analyse the associated impacts on anomalies and biases of European 2-m air temperature (TAS) and precipitation rate (PR). Five RCM runs stem from the EURO-CORDEX ensemble while three RCMs are WRF models with different nudging realizations, all of them driven by ERA-Interim for the period 1981?2010. The detected blocking systems are allocated to three sectors of the Euro-Atlantic region, allowing for a characterization of distinctive blocking-related TAS and PR anomalies. Our results indicate some misrepresentation of atmospheric blocking over the EURO-CORDEX domain, as compared to the driving reanalysis. Most of the RCMs showed fewer blocks than the driving data, while the blocking misdetection was negligible for RCMs strongly conditioned to the driving data. A higher resolution of the RCMs did not improve the representation of atmospheric blocking. However, all RCMs are able to reproduce the basic anomaly structure of TAS and PR connected to blocking. Moreover, the associated anomalies do not change substantially after correcting for the misrepresentation of blocking in RCMs. The overall model bias is mainly determined by pattern biases in the representations of surface parameters during non-blocking situations. Biases in blocking detections tend to have a secondary influence in the overall bias due to compensatory effects of missed blockings and non-blockings. However, they can lead to measurable effects in the presence of a strong blocking underestimation.This work was funded by the Austrian Science Fund (FWF) under the project: Understanding Contrasts in high Mountain hydrology in Asia (UNCOMUN: I 1295-N29). This research was supported by the Faculty of Environmental, Regional and Educational Sciences (URBI), University of Graz, as well as the Federal Ministry of Science, Research and Economy (BMWFW) by funding the OeAD Grant Marietta Blau. This work was partially supported (JMG and SH) by the project MULTI-SDM (CGL2015-66583- R, MINECO/FEDER). DB was supported by the PALEOSTRAT (CGL2015-69699-R) project funded by the Spanish Ministry of Economy and Competitiveness (MINECO)

Polarised Quark Distributions in the Nucleon from Semi-Inclusive Spin Asymmetries

We present a measurement of semi-inclusive spin asymmetries for positively and negatively charged hadrons from deep inelastic scattering of polarised muons on polarised protons and deuterons in the range $0.003$1 GeV$^2$. Compared to our previous publication on this subject, with the new data the statistical errors have been reduced by nearly a factor of two. From these asymmetries and our inclusive spin asymmetries we determine the polarised quark distributions of valence quarks and non-strange sea quarks at $Q^2$=10 GeV$^2$. The polarised $u$ valence quark distribution, $\Delta u_v(x)$, is positive and the polarisation increases with $x$. The polarised $d$ valence quark distribution, $\Delta d_v(x)$, is negative and the non-strange sea distribution, $\Delta \bar q(x)$, is consistent with zero over the measured range of $x$. We find for the first moments $\int_0^1 \Delta u_v(x) dx = 0.77 \pm 0.10 \pm 0.08$, $\int_0^1 \Delta d_v(x) dx = -0.52 \pm 0.14 \pm 0.09$ and $\int_0^1 \Delta \bar q(x) dx= 0.01 \pm 0.04 \pm 0.03$, where we assumed $\Delta \bar u(x) = \Delta \bar d(x)$. We also determine for the first time the second moments of the valence distributions $\int_0^1 x \Delta q_v(x) dx$.Comment: 17 page

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Search for the decay modes D^0 → e^+e^-, D^0 → μ^+μ^-, and D^0 → e^±μ∓

We present searches for the rare decay modes D^0→e^+e^-, D^0→μ^+μ^-, and D^0→e^±μ^∓ in continuum e^+e^-→cc events recorded by the BABAR detector in a data sample that corresponds to an integrated luminosity of 468  fb^(-1). These decays are highly Glashow–Iliopoulos–Maiani suppressed but may be enhanced in several extensions of the standard model. Our observed event yields are consistent with the expected backgrounds. An excess is seen in the D^0→μ^+μ^- channel, although the observed yield is consistent with an upward background fluctuation at the 5% level. Using the Feldman–Cousins method, we set the following 90% confidence level intervals on the branching fractions: B(D^0→e^+e^-)<1.7×10^(-7), B(D^0→μ^+μ^-) within [0.6,8.1]×10^(-7), and B(D^0→e^±μ^∓)<3.3×10^(-7)

Evidence for an excess of B -> D(*) Tau Nu decays

Based on the full BaBar data sample, we report improved measurements of the ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or mu. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) = 0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0 sigma and 2.7 sigma, respectively. Taken together, our results disagree with these expectations at the 3.4 sigma level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model. We also report the observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.Comment: Expanded section on systematics, text corrections, improved the format of Figure 2 and included the effect of the change of the Tau polarization due to the charged Higg

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi

We present a study of ten B-meson decays to a D(*), a proton-antiproton pair, and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs. Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B- -> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi- pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first observations. The branching fractions for 3- and 5-body decays are suppressed compared to 4-body decays. Kinematic distributions for 3-body decays show non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4) MeV/c2, respectively, where the first (second) errors are statistical (systematic). For 5-body decays, mass projections are similar to phase space expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration