pinecone/core-2020-05-10-deduplication huggingface dataset:
Genetic variability commonly affecting neurodegeneration and neuroinflammation

Loss of nerve cells and axons is a common feature of common complex 
neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. However, 
also Multiple Sclerosis (MS), primarily an autoimmune disorder, has a prominent 
neurodegenerative component. In complex disorders, many components affecting 
disease development and disease progression in combination make up the overall risk. 
In general, we divide these factors into inherited genetic factors and environmental 
factors. In addition, there are sometimes complex gene-environment interactions that 
make it difficult to identify individual risk components.



In this thesis, I have focused on a translational approach to find genetic determinants of 
nerve cell survival in a simplified experimental model of nerve injury-induced 
neurodegeneration. The aim has been to find novel genes/pathways whose relevance 
subsequently can be tested in human disease. Through various genetic mapping 
approaches I demonstrate a strong inverse correlation between neuronal survival and 
expression and protein levels of an enzyme involved in detoxification of certain 
oxidation by-products. This enzyme, Glutathione S-Transferase alpha 4 (Gsta4), is 
highly efficient in catalysing the reduction of the neurotoxic aldehyde 4-
hydroxynonenal (HNE), which is generated during lipid peroxidation and has 
previously been implicated in the pathogenesis of various neurodegenerative disorders.



The relevance of this mechanism was also tested in a model of traumatic brain injury, 
where Gsta4 levels inversely correlate with degree of neuronal loss as well. In addition, 
rats with higher Gsta4 levels have a more favourable outcome after injection of HNE 
directly into the cortex. Taken together, these two studies provide strong support for the 
notion that the identified pathway is highly important for ability to cope with oxidative 
stress and in turn of relevance for nerve cell survival in different types of acute injury.



Finally, a possible role for Gsta4 is tested in experimental autoimmune 
encephalomyelitis (EAE), a model of MS. No discernible clinical effect was observed 
between congenic rats with higher Gsta4 expression and the parental strain. However, 
lower Gsta4 expression was associated with a stronger autoantibody response. Protein 
modifications by HNE have in other inflammatory models been documented to induce 
a stronger antibody response, which is consistent with the obtained results. Intrathecal 
antibody production is an important diagnostic marker in MS, and hypothetically the 
HNE pathway can play a role for disease course through both neurotoxicity and 
amplification of the immune response. This was tested in a large case control cohort of 
MS, where suggested associations both to clinical and immune phenotypes were found. 
In summary, the results presented encourage further studies on the Gsta4-HNE pathway 
both in conditions of acute nerve injury and autoimmune neuroinflammation
Search for extra dimensions using diphoton events in 7 TeV proton-proton collisions with the ATLAS detector ATLAS Collaboration

Using data recorded in 2011 with the ATLAS detector at the Large Hadron Collider, a search for evidence of extra spatial dimensions has been performed through an analysis of the diphoton final state. The analysis uses data corresponding to an integrated luminosity of 2.12 fb(-1) of root s = 7 TeV proton-proton collisions. The diphoton invariant mass (m(gamma gamma)) spectrum is observed to be in good agreement with the expected Standard Model background. In the large extra dimension scenario of Arkani-Hamed, Dimopoulos and Dvali, the results provide 95% CL lower limits on the fundamental Planck scale between 2.27 and 3.53 TeV, depending on the number of extra dimensions and the theoretical formalism used. The results also set 95% CL lower limits on the lightest Randall-Sundrum graviton mass of between 0.79 and 1.85 TeV, for values of the dimensionless coupling k/(M) over bar (Pl) varying from 0.01 to 0.1. Combining with previously published ATLAS results from the dielectron and dimuon final states, the 95% CL lower limit on the Randall-Sundrum graviton mass for k/(M) over bar (Pl) = 0.01 (0.1) is 0.80 (1.95) TeV
Evolution of Bacterial Community in a Full-scale Biotrickling Filter by Fluorescence in Situ Hybridization (FISH)

The performance of a full-scale biotrickling system for the treatment of exhaust gases from two different paint sources at a furniture facility, was investigated applying Fluorescense in situ hybridization (FISH). This technique allowed the detection of major bacteria groups and, therefore, helped in understanding complex microbial communities. The results indicated that Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, and Deltaproteobacteria were more predominant than Firmicutes and Actiniobacterias. In addition, a variation in the composition of the bacterial community throughout the time of operation and with the paint source was observed. Betaproteobacteria showed similar relative abundance in all analyzed days. However, Gammaproteobacteria, relevant group in the degradation of VOCs, fluctuated with operational changes and the relative abundance of Alphaproteobacteria decreased when the composition of pollutants of the emission source was changed
Microwave-assisted, mild, facile, and rapid one-pot three-component synthesis of some novel pyrano2,3-dpyrimidine-2,4,7-triones

Novel pyrano2,3-dpyrimidine-2,4,7-triones were synthesized in 90-97% yield via a three-component reaction of an aromatic aldehyde, Meldrums acid, and barbituric acid in the presence of 10 mol % K2CO3 under microwave irradiation. This is the first protocol to be reported for the synthesis of title compounds and the significant features of the present protocol are simplicity, high yields, short reaction time, involvement of aqueous work-up procedure, environmentally benign nature, and no chromatographic purification. Â© 2012 Elsevier Ltd. All rights reserved
Guest editors' introduction: People management and emerging market multinationals

© 2014 Wiley Periodicals, Inc. There is a very extensive body of literature on how multinationals manage their people in different national contexts. However, the bulk of this literature focuses on the case of multinationals from the advanced industrial economies, and to a considerable extent, the United States. Very much less has been written on multinationals with their country of origin being an emerging market, and what little there is has focused on a very limited number of preferred cases. The growing importance of emerging economies has led to an upsurge of strategy research on the topic (Wright, Filatotchev, Hoskisson, & Peng, 2005); however, research on human resource management has not paid enough attention to emerging market multinational enterprises (EMNEs). Many EMNEs tend to be smaller in size with considerably fewer resources and less international experience than their counterparts from developed markets, limiting their ability to transfer management practice across their subsidiaries (Thite, Wilkinson, & Shah, 2012), although there are important exceptions to this rule. This introductory article seeks to contribute to the emerging body of literature in this area, through seeking to encourage fresh insights, particularly on the varieties of people management encountered in different national contexts
Diversity of TH cytokine profiles in patients with chronic rhinosinusitis : a multicenter study in Europe, Asia, and Oceania

Background: To date, no study has evaluated the diversity of T-H cell cytokine patterns of patients with chronic rhinosinusitis (CRS) among centers in different continents using identical methods. 
Objective: We sought to assess T-H cytokine profiles in patients with CRS from Europe, Asia, and Australia. 
Methods: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP; n 5 435) and control subjects (n 5 138) were recruited from centers in Adelaide, Benelux, Berlin, Beijing, Chengdu, and Tochigi. Nasal mucosal concentrations of T(H)2, T(H)17, and T(H)1 cytokines; eosinophilic cationic protein (ECP); myeloperoxidase (MPO); IL-8; and tissue total and Staphylococcus aureus enterotoxin (SE)-specific IgE were measured by using identical tools. 
Results: Combinations of T(H)1/T(H)2/T(H)17 cytokine profiles in patients with CRSwNP varied considerably between regions. CRSwNP tissues from patients from Benelux, Berlin, Adelaide, and Tochigi were T(H)2 biased, whereas those from Beijing mainly demonstrated T(H)2/T(H)1/T(H)17 mixed patterns, and patients from Chengdu showed an even lower T(H)2 expression. Concentrations of IL-8 and tissue total IgE in patients with CRSwNP were significantly higher than those in control subjects in all regions. More than 50% of patients with CRSwNP in Benelux, Berlin, Adelaide, and Tochigi showed a predominantly eosinophilic endotype compared with less than 30% of patients in Beijing and Chengdu. SE-specific IgE was found in significantly greater numbers in patients with CRSwNP from Benelux, Adelaide, and Tochigi and significantly lower numbers in patients from Beijing and Chengdu. Moreover, the T(H)1/T(H)2/T(H)17 cytokine profiles in patients with CRSsNP showed diversity among the 6 regions. 
Conclusion: T-H cytokine levels, eosinophilic/neutrophilic patterns, and SE-specific IgE expressions show extreme diversity among patients with CRS from Europe, Asia, and Oceania
The Salmonella effector SteD mediates MARCH8-1 dependent ubiquitination of MHC II molecules and inhibits T cell activation

The SPI-2 type III secretion system (T3SS) of intracellular Salmonella enterica translocates effector proteins into mammalian cells. Infection of antigen-presenting cells results in SPI-2 T3SS-dependent ubiquitination and reduction of surface-localized mature MHC class II (mMHCII). We identify the effector SteD as required and sufficient for this process. In Mel Juso cells, SteD localized to the Golgi network and vesicles containing the E3 ubiquitin ligase MARCH8 and mMHCII. SteD caused MARCH8-dependent ubiquitination and depletion of surface mMHCII. One of two transmembrane domains and the C-terminal cytoplasmic region of SteD mediated binding to MARCH8 and mMHCII, respectively. Infection of dendritic cells resulted in SteD-dependent depletion of surface MHCII, the co-stimulatory molecule B7.2, and suppression of T cell activation. SteD also accounted for suppression of T cell activation during Salmonella infection of mice. We propose that SteD is an adaptor, forcing inappropriate ubiquitination of mMHCII by MARCH8 and thereby suppressing T cell activation
Current use and Cochrane guidance on selection of social theories for systematic reviews of complex interventions.

Published onlineJOURNAL ARTICLEThis is the author accepted manuscript. The final version is available from  Elsevier via the DOI in this record.OBJECTIVE: To identify examples of how social theories are used in systematic reviews of complex interventions to inform production of Cochrane Guidance. STUDY DESIGN AND SETTING: Secondary analysis of published/unpublished examples of theories of social phenomena for use in reviews of complex interventions identified through scoping searches, engagement with key authors and methodologists supplemented by snowballing and reference searching. Theories were classified (low-level, mid-range, grand). RESULTS: Over 100 theories were identified with evidence of proliferation over the last 5 years. New low-level theories (tools, taxonomies etc.) have been developed for classifying and reporting complex interventions. Numerous mid-range theories are used; one example demonstrated how control theory had changed the review's findings. Review-specific logic models are increasingly used, but these can be challenging to develop. New low-level and mid-range psychological theories of behaviour change are evolving. No reviews using grand theory (e.g. feminist theory) were identified. We produced a searchable Wiki, Mendeley Inventory and Cochrane Guidance. CONCLUSIONS: Use of low-level theory is common and evolving; incorporation of mid-range theory is still the exception rather than the norm. Methodological work is needed to evaluate the contribution of theory. Choice of theory reflects personal preference; application of theory is a skilled endeavour
Measurements of the S-wave fraction in $B^{0}\rightarrow K^{+}\pi^{-}\mu^{+}\mu^{-}$ decays and the $B^{0}\rightarrow K^{\ast}(892)^{0}\mu^{+}\mu^{-}$ differential branching fraction

A measurement of the differential branching fraction of the decay ${B^{0}\rightarrow K^{\ast}(892)^{0}\mu^{+}\mu^{-}}$ is presented together with a determination of the S-wave fraction of the $K^+\pi^-$ system in the decay $B^{0}\rightarrow K^{+}\pi^{-}\mu^{+}\mu^{-}$. The analysis is based on $pp$-collision data corresponding to an integrated luminosity of 3\,fb$^{-1}$ collected with the LHCb experiment. The measurements are made in bins of the invariant mass squared of the dimuon system, $q^2$. Precise theoretical predictions for the differential branching fraction of $B^{0}\rightarrow K^{\ast}(892)^{0}\mu^{+}\mu^{-}$ decays are available for the $q^2$ region $1.1 < q^2 < 6.0\,{\rm GeV}^2/c^4$. In this $q^2$ region, for the $K^+\pi^-$ invariant mass range $796 < m_{K\pi} < 996\,{\rm MeV}/c^2$, the S-wave fraction of the $K^+\pi^-$ system in $B^{0}\rightarrow K^{+}\pi^{-}\mu^{+}\mu^{-}$ decays is found to be \begin{equation*} F_{\rm S} = 0.101 \pm 0.017({\rm stat}) \pm 0.009 ({\rm syst}), \end{equation*} and the differential branching fraction of $B^{0}\rightarrow K^{\ast}(892)^{0}\mu^{+}\mu^{-}$ decays is determined to be \begin{equation*} {\rm d}\mathcal{B}/{\rm d} q^2 = (0.392_{\,-0.019}^{\,+0.020}({\rm stat})\pm{0.010}({\rm syst})\pm0.027({\rm norm}))\times 10^{-7}c^{4}/{\rm GeV}^{2}. \end{equation*} The differential branching fraction measurements presented are the most precise to date and are found to be in agreement with Standard Model predictions
Search for the Standard Model Higgs boson decay to mu+mu- with the ATLAS detector

A search is reported for Higgs boson decay to μ+μ− using data with an integrated luminosity of 24.8 fb−124.8 fb−1 collected with the ATLAS detector in pp collisions at √s=7and 8 TeV at the CERN Large Hadron Collider. The observed dimuon invariant mass distribution is consistent with the Standard Model background-only hypothesis in the 120–150 GeV search range. For a Higgs boson with a mass of 125.5 GeV, the observed (expected) upper limit at the 95% confidence level is 7.0 (7.2) times the Standard Model expectation. This corresponds to an upper limit on the branching ratio BR(H→μ+μ−)BR(H→μ+μ−) of 1.5×10−31.5×10‾³.G. Aad … P. Jackson … L. Lee … A. Petridis … N. Soni ... M. White ... et al. (The ATLAS Collaboration
Lipopolysaccharide attenuates mRNA levels of several adenylyl cyclase isoforms in vivo

AbstractSignals that elevate intracellular levels of cyclic adenosine monophosphate (cAMP) are among the factors that control lipopolysaccharide (LPS)-mediated inflammatory mediator production by macrophages. cAMP signaling is also involved in maintaining body functions that are commonly impaired in sepsis, including the endothelial cell barrier function and heart function. Several agents successfully used for sepsis intervention target cAMP signaling, and it was recently shown that liver and lung may be protected from inflammation injury by cAMP-elevating phosphodiesterase inhibitors. Here, we show that LPS attenuates adenylyl cyclase (AC) mRNA levels in liver, lung, heart, spleen and kidney in an animal model of endotoxemia, and in macrophages from liver and lung. In particular, AC5, AC6, AC7 and AC9 mRNA were reduced in most tissues examined and in tissue macrophages. In Kupffer cells, prostaglandin E2-mediated cAMP production was inhibited by LPS treatment. The reduction in AC mRNA by LPS would be expected to lead to a lowered potential for cAMP production in most organs, and in particular, changes in AC6 mRNA may affect endothelial cell barrier function and heart function. In contrast, AC4 mRNA was elevated in heart and lung. The present work indicates a possible mechanism for LPS-mediated alteration of cAMP signaling in vivo
On global solution to the Klein–Gordon–Hartree equation below energy space

AbstractIn this paper, we consider the Cauchy problem for Klein–Gordon equation with a cubic convolution nonlinearity in R3. By making use of Bourgain's method in conjunction with a precise Strichartz estimate of S. Klainerman and D. Tataru, we establish the Hs (s<1) global well-posedness of the Cauchy problem for the cubic convolution defocusing Klein–Gordon–Hartree equation. Before arriving at the previously discussed conclusion, we obtain global solution for this non-scaling equation with small initial data in Hs0×Hs0−1 where s0=γ6 but not γ2−1, for this equation that we consider is a subconformal equation in some sense. In doing so a number of nonlinear prior estimates are already established by using Bony's decomposition, flexibility of Klein–Gordon admissible pairs which are slightly different from that of wave equation and a commutator estimate. We establish this commutator estimate by exploiting cancellation property and utilizing Coifman and Meyer multilinear multiplier theorem. As far as we know, it seems that this is the first result on low regularity for this Klein–Gordon–Hartree equation
Luminescence dating of glacial advances at Lago Buenos Aires (∼46 °S), Patagonia

AbstractUnderstanding the timing of past glacial advances in Patagonia is of global climatic importance because of the insight this can provide into the influence on glacier behaviour of changes in temperature and precipitation related to the Southern Westerlies. In this paper we present new luminescence ages determined using single grains of K-feldspar from proglacial outwash sediments that were deposited by the Patagonian Ice Sheet around Lago Buenos Aires (∼46 °S), east of the contemporary Northern Patagonian Icefield. The new luminescence ages indicate that major outwash accumulations formed around ∼110 ± 20 ka to 140 ± 20 ka and that these correspond to the Moreno I and II moraine ridges, which were previously dated using cosmogenic isotope dating to 150 ± 30 ka. Luminescence dating at Lago Buenos Aires has also identified outwash sediments that were deposited during glacial advances ∼30.8 ± 5.7 ka and ∼34.0 ± 6.1 ka (MIS 3) that are not recorded in the moraine record. Younger outwash accumulations were then deposited between ∼14.7 ± 2.1 and 26.2 ± 1.6 ka which correspond to the Fenix I – V moraine ridges. The combined chronology suggests that glacial advances occurred ∼110 ± 20 ka to 150 ± 30 ka (MIS 6), ∼30.8 ± 5.7 ka to ∼34.0 ± 6.1 ka (MIS 3), and ∼14.7 ± 2.1 to 26.2 ± 1.6 ka (MIS 2) at Lago Buenos Aires. Overall luminescence dating using single grains of K-feldspar has excellent potential to contribute towards the ever-increasing geochronological dataset constraining the timings of glacial advances in Patagonia
Search for W′ decaying to tau lepton and neutrino in proton–proton collisions at s=8 TeV

AbstractThe first search for a heavy charged vector boson in the final state with a tau lepton and a neutrino is reported, using 19.7 fb−1 of LHC data at s=8 TeV. A signal would appear as an excess of events with high transverse mass, where the standard model background is low. No excess is observed. Limits are set on a model in which the W′ decays preferentially to fermions of the third generation. These results substantially extend previous constraints on this model. Masses below 2.0 to 2.7 TeV are excluded, depending on the model parameters. In addition, the existence of a W′ boson with universal fermion couplings is excluded at 95% confidence level, for W′ masses below 2.7 TeV. For further reinterpretation a model-independent limit on potential signals for various transverse mass thresholds is also presented
Strangeness enhancement in p–A collisions: Consequences for the interpretation of strangeness production in A–A collisions

AbstractPublished measurements of semi-inclusive Λ production in p–Au collisions at the AGS are used to estimate the yields of singly strange hadrons in nucleus–nucleus (A–A) collisions. Results of a described extrapolation technique are shown and compared to measurements of K+ production in Si–Al, Si–Au, and Au–Au collisions at the AGS and net Λ production in S–S, S–Ag, Pb–Pb, and inclusive p–A collisions at the SPS. The extrapolations can account for more than 75% of the measured strange particle yields in all of the studied systems except for very central Au+Au collisions at the AGS where RQMD comparisons suggest large re-scattering contributions
Instability of Schwarzschild–AdS black hole in Einstein–Weyl gravity

AbstractWe investigate the classical stability of Schwarzschild–AdS black hole in a massive gravity theory of the Einstein–Weyl gravity. It turns out that the linearized Einstein tensor perturbations exhibit unstable modes featuring the Gregory–Laflamme instability of five-dimensional AdS black string, in contrast to the stable Schwarzschild–AdS black hole in Einstein gravity. We point out that the instability of the black hole in the Einstein–Weyl gravity arises from the massiveness but not a feature of fourth-order derivative theory giving ghost states