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The influence of an ac current of arbitrary amplitude and frequency on the mixed-state dc-voltage-ac-drive tiltingratchet response of a superconducting film with uniaxial cosine pinning potential at finite temperature is theoretically investigated. The results are obtained in the single-vortex approximation, within the frame of an exact solution of the Langevin equation for non-interacting vortices. Both experimentally achievable, the dc ratchet response and absorbed ac power are predicted to demonstrate a pronounced filter-like behavior at microwave frequencies. Based on our findings, we propose a cut-off filter and discuss its operating curves as functions of the driving parameters, i.e, ac amplitude, frequency, and dc bias. The predicted results can be examined, e.g, on superconducting films with a washboard pinning potential landscape.
A measurement of the multi-strange Ξ− and Ω− baryons and their antiparticles by the ALICE experiment at the CERN Large Hadron Collider (LHC) is presented for inelastic proton–proton collisions at a centre-of-mass energy of 7 TeV. The transverse momentum (pT) distributions were studied at mid-rapidity (|y|<0.5) in the range of 0.6<pT<8.5 GeV/c for Ξ− and Ξ¯+ baryons, and in the range of 0.8<pT<5 GeV/c for Ω− and Ω¯+. Baryons and antibaryons were measured as separate particles and we find that the baryon to antibaryon ratio of both particle species is consistent with unity over the entire range of the measurement. The statistical precision of the current data has allowed us to measure a difference between the mean pT of Ξ− (Ξ¯+) and Ω− (Ω¯+). Particle yields, mean pT, and the spectra in the intermediate pT range are not well described by the PYTHIA Perugia 2011 tune Monte Carlo event generator, which has been tuned to reproduce the early LHC data. The discrepancy is largest for Ω− (Ω¯+). This PYTHIA tune approaches the pT spectra of Ξ− and Ξ¯+ baryons below pT<0.85 GeV/c and describes the Ξ− and Ξ¯+ spectra above pT>6.0 GeV/c. We also illustrate the difference between the experimental data and model by comparing the corresponding ratios of (Ω−+Ω¯+)/(Ξ−+Ξ¯+) as a function of transverse mass.
Background: The transcription factor T-bet is pivotal for initiation of Th1-related immunoactivation. Identification of novel genes directly regulated by T-bet is crucial.
Results: Genome-wide analysis and subsequent experiments revealed that T-bet up-regulates IL-36γ/IL-1F9 in myeloid cells.
Conclusion: IL-1-related IL-36γ is a direct T-bet target in myeloid cells.
Significance: Observations suggest that IL-36γ , besides IFNγ, contributes to T-bet functions in immunopathology
By concerted action in dendritic (DC) and T cells, T-box expressed in T cells (T-bet, Tbx21) is pivotal for initiation and perpetuation of Th1 immunity. Identification of novel T-bet-regulated genes is crucial for further understanding the biology of this transcription factor. By combining siRNA technology with genome-wide mRNA expression analysis, we sought to identify new T-bet-regulated genes in predendritic KG1 cells activated by IL-18. One gene robustly dependent on T-bet was IL-36γ, a recently described novel IL-1 family member. Promoter analysis revealed a T-bet binding site that, along with a κB site, enables efficient IL-36γ induction. Using knock-out animals, IL-36γ reliance on T-bet was extended to murine DC. IL-36γ expression by human myeloid cells was confirmed using monocyte-derived DC and M1 macrophages. The latter model was employed to substantiate dependence of IL-36γ on endogenous T-bet in human primary cells. Ectopic expression of T-bet likewise mediated IL-36γ production in HaCaT keratinocytes that otherwise lack this transcription factor. Additional experiments furthermore revealed that mature IL-36γ has the capability to establish an inflammatory gene expression profile in human primary keratinocytes that displays enhanced mRNA levels for TNFα, CCL20, S100A7, inducible NOS, and IL-36γ itself. Data presented herein shed further light on involvement of T-bet in innate immunity and suggest that IL-36γ, besides IFNγ, may contribute to functions of this transcription factor in immunopathology.
This paper describes free relative constructions in Modern Standard Arabic (henceforth, MSA) and aims to provide an HPSG analysis for them. MSA has two types of free relative constructions. One, which is introduced by the complementizer ?allaði, looks just like a relative clause. The other, which is introduced by the elements man and maa, which also appear to be complementizers, does not look like a relative clause. Both types can be analysed in term of unary-branching structures (as NPs consisting just of a CP). In ?allaði free relatives, the NP and the value of SLASH can be coindexed via the value of MOD on the CP. In man and maa free relatives, the NP and the value of SLASH must be coindexed directly.
Heavy flavour decay muon production at forward rapidity in proton–proton collisions at √s=7 TeV
(2012)
The production of muons from heavy flavour decays is measured at forward rapidity in proton–proton collisions at √s=7 TeV collected with the ALICE experiment at the LHC. The analysis is carried out on a data sample corresponding to an integrated luminosity Lint=16.5 nb−1. The transverse momentum and rapidity differential production cross sections of muons from heavy flavour decays are measured in the rapidity range 2.5<y<4, over the transverse momentum range 2<pt<12 GeV/c. The results are compared to predictions based on perturbative QCD calculations.
Lantibiotics are peptide-derived antibiotics that inhibit the growth of Gram-positive bacteria via interactions with lipid II and lipid II-dependent pore formation in the bacterial membrane. Due to their general mode of action the Gram-positive producer strains need to express immunity proteins (LanI proteins) for protection against their own lantibiotics. Little is known about the immunity mechanism protecting the producer strain against its own lantibiotic on the molecular level. So far, no structures have been reported for any LanI protein. We solved the structure of SpaI, a LanI protein from the subtilin producing strain Bacillus subtilis ATCC 6633. SpaI is a 16.8-kDa lipoprotein that is attached to the outside of the cytoplasmic membrane via a covalent diacylglycerol anchor. SpaI together with the ABC transporter SpaFEG protects the B. subtilis membrane from subtilin insertion. The solution-NMR structure of a 15-kDa biologically active C-terminal fragment reveals a novel fold. We also demonstrate that the first 20 N-terminal amino acids not present in this C-terminal fragment are unstructured in solution and are required for interactions with lipid membranes. Additionally, growth tests reveal that these 20 N-terminal residues are important for the immunity mediated by SpaI but most likely are not part of a possible subtilin binding site. Our findings are the first step on the way of understanding the immunity mechanism of B. subtilis in particular and of other lantibiotic producing strains in general.
DNA translocators of natural transformation systems are complex systems critical for the uptake of free DNA and provide a powerful mechanism for adaptation to changing environmental conditions. In natural transformation machineries, outer membrane secretins are suggested to form a multimeric pore for the uptake of external DNA. Recently, we reported on a novel structure of the DNA translocator secretin complex, PilQ, in Thermus thermophilus HB27 comprising a stable cone and cup structure and six ring structures with a large central channel. Here, we report on structural and functional analyses of a set of N-terminal PilQ deletion derivatives in T. thermophilus HB27. We identified 136 N-terminal residues exhibiting an unusual ααβαββα fold as a ring-building domain. Deletion of this domain had a dramatic effect on twitching motility, adhesion, and piliation but did not abolish natural transformation. These findings provide clear evidence that the pilus structures of T. thermophilus are not essential for natural transformation. The truncated complex was not affected in inner and outer membrane association, indicating that the 136 N-terminal residues are not essential for membrane targeting. Analyses of complex formation of the truncated PilQ monomers revealed that the region downstream of residue 136 is required for multimerization, and the region downstream of residue 207 is essential for monomer stability. Possible implications of our findings for the mechanism of DNA uptake are discussed.
This paper presents an HPSG formalisation of how the ellipsis of case-marking affects the focus of the clause in Japanese. We restrict our attention to the nominative and accusative markers ga and o, and in view of the fact that the ellipsis effects on focushood vary between 1) ga and o and 2) different argument structures of the head verb, develop an essentially lexicalist account that combines both aspects, in which the implicit focus argument position is specified in the predicate. We argue that if a constituent is an implicit focus it does not, while if one is not it does, require a case-marker to be focused.
This paper presents an analysis of Danish free relative constructions. Fol- lowing Bresnan and Grimshaw (1978) we will adopt a wh-head (in Danish hv-head) analysis where the hv-phrase is the head of an NP. Also following Bresnan and Grimshaw (1978) we will propose an analysis which does not involve a filler-gap dependency between the hv-phrase and the gap in the sis- ter clause. Instead we will propose that the gap in the sister clause is bound off by a constructional constraint. In this way the analysis will be shown to differ from previous HPSG wh-head analyses of free relatives.
This paper presents a left-branching constructionalist grammar design where the phrase structure tree does not correspond to the conventional constituent structure. The constituent structure is rather reflected by embeddings on a feature STACK. The design is compatible with incremental processing, as words are combined from left to right, one by one, and it gives a simple account of long distance dependencies, where the extracted element is assumed to be dominated by the extraction site. It is motivated by psycholinguistic findings.
The demand to develop convergent technology platforms, such as bio-functionalized medical devices, is rapidly increasing. However, the loss of biological function of the effector molecules during sterilization represents a significant and general problem. Therefore, we have developed and characterized a nano-coating (NC) formulation capable of maintaining the functionality of proteins on biological-device combination products. As a proof of concept, the NC preserved the structural and functional integrity of an otherwise highly fragile antibody immobilized on polyurethane during deleterious sterilizing irradiation (≥ 25 kGy). The NC procedure enables straight-forward terminal sterilization of bio-functionalized materials while preserving optimal conditioning of the bioactive surface.
Health-care personnel (HCP) are exposed to infectious diseases throughout the course of their work. The concerns of pregnant HCP are considerable because certain otherwise mild infections may affect fetal development. We studied 424 pregnant HCP at the University Hospital Frankfurt / Germany between March 2007 and July 2011. Serological tests were carried out for varicella zoster virus (VZV), measles, mumps, rubella (MMR), cytomegalovirus (CMV) and parvovirus B19. Our overall seroprevalence data with regard to VZV, MMR, CMV and parvovirus B 19 corresponded to the general population. It was striking that, only 57.1% of the study population was immune against the four vaccine-preventable diseases (MMR, VZV). Our study suggests that a comprehensive approach to improving the vaccination status of said HCP before pregnancy is paramount.
In this paper I use the formal framework of minimalist grammars to implement a version of the traditional approach to ellipsis as 'deletion under syntactic (derivational) identity', which, in conjunction with canonical analyses of voice phenomena, immediately allows for voice mismatches in verb phrase ellipsis, but not in sluicing. This approach to ellipsis is naturally implemented in a parser by means of threading a state encoding a set of possible antecedent derivation contexts through the derivation tree. Similarities between ellipsis and pronominal resolution are easily stated in these terms. In the context of this implementation, two approaches to ellipsis in the transformational community are naturally seen as equivalent descriptions at different levels: the LF-copying approach to ellipsis resolution is best seen as a description of the parser, whereas the phonological deletion approach a description of the underlying relation between form and meaning.
The spatial configuration of initial partons in high multiplicity proton–proton scatterings at 14 TeV is assumed as three randomly positioned “hot spots”. The parton momentum distribution in the hot spots is calculated by HIJING2.0 with some modifications. This initial condition causes not only large eccentricity ϵ2 but also triangularity ϵ3 and the correlation of ϵ2−ϵ3 event-plane angles. The final elliptic flow v2, triangular flow v3, and the correlation of v2−v3 event-plane angles are calculated by using the parton cascade model BAMPS to simulate the space–time parton evolution. Our results show that the v2−v3 correlation is different from that of ϵ2−ϵ3. This finding indicates that translations of different Fourier components of the initial spatial asymmetry to the final flow components are not independent. A dynamical correlation between the elliptic and triangular flow appears during the collective expansion.
Protein-tyrosine phosphatases (PTPs) and protein-tyrosine kinases co-regulate cellular processes. In pathogenic bacteria, they are frequently exploited to act as key virulence factors for human diseases. Mycobacterium tuberculosis, the causative organism of tuberculosis, secretes a low molecular weight PTP (LMW-PTP), MptpA, which is required for its survival upon infection of host macrophages. Although there is otherwise no sequence similarity of LMW-PTPs to other classes of PTPs, the phosphate binding loop (P-loop) CX5R and the loop containing a critical aspartic acid residue (D-loop), required for the catalytic activity, are well conserved. In most high molecular weight PTPs, ligand binding to the P-loop triggers a large conformational reorientation of the D-loop, in which it moves ∼10 Å, from an “open” to a “closed” conformation. Until now, there have been no ligand-free structures of LMW-PTPs described, and hence the dynamics of the D-loop have remained largely unknown for these PTPs. Here, we present a high resolution solution NMR structure of the free form of the MptpA LMW-PTP. In the absence of ligand and phosphate ions, the D-loop adopts an open conformation. Furthermore, we characterized the binding site of phosphate, a competitive inhibitor of LMW-PTPs, on MptpA and elucidated the involvement of both the P- and D-loop in phosphate binding. Notably, in LMW-PTPs, the phosphorylation status of two well conserved tyrosine residues, typically located in the D-loop, regulates the enzyme activity. PtkA, the kinase complementary to MptpA, phosphorylates these two tyrosine residues in MptpA. We characterized the MptpA-PtkA interaction by NMR spectroscopy to show that both the P- and D-loop form part of the binding interface.
Measurements of the sphericity of primary charged particles in minimum bias proton--proton collisions at s√=0.9, 2.76 and 7 TeV with the ALICE detector at the LHC are presented. The observable is linearized to be collinear safe and is measured in the plane perpendicular to the beam direction using primary charged tracks with pT≥0.5 GeV/c in |η|≤0.8. The mean sphericity as a function of the charged particle multiplicity at mid-rapidity (Nch) is reported for events with different pT scales ("soft" and "hard") defined by the transverse momentum of the leading particle. In addition, the mean charged particle transverse momentum versus multiplicity is presented for the different event classes, and the sphericity distributions in bins of multiplicity are presented. The data are compared with calculations of standard Monte Carlo event generators. The transverse sphericity is found to grow with multiplicity at all collision energies, with a steeper rise at low Nch, whereas the event generators show the opposite tendency. The combined study of the sphericity and the mean pT with multiplicity indicates that most of the tested event generators produce events with higher multiplicity by generating more back-to-back jets resulting in decreased sphericity (and isotropy). The PYTHIA6 generator with tune PERUGIA-2011 exhibits a noticeable improvement in describing the data, compared to the other tested generators.
Background: Acoustic Radiation Force Impulse (ARFI)-imaging is an ultrasound-based elastography method enabling quantitative measurement of tissue stiffness. The aim of the present study was to evaluate sensitivity and specificity of ARFI-imaging for differentiation of thyroid nodules and to compare it to the well evaluated qualitative real-time elastography (RTE).
Methods: ARFI-imaging involves the mechanical excitation of tissue using acoustic pulses to generate localized displacements resulting in shear-wave propagation which is tracked using correlation-based methods and recorded in m/s. Inclusion criteria were: nodules $5 mm, and cytological/histological assessment. All patients received conventional ultrasound, real-time elastography (RTE) and ARFI-imaging.
Results: One-hundred-fifty-eight nodules in 138 patients were available for analysis. One-hundred-thirty-seven nodules were benign on cytology/histology, and twenty-one nodules were malignant. The median velocity of ARFI-imaging in the healthy thyroid tissue, as well as in benign and malignant thyroid nodules was 1.76 m/s, 1.90 m/s, and 2.69 m/s, respectively. While no significant difference in median velocity was found between healthy thyroid tissue and benign thyroid nodules, a significant difference was found between malignant thyroid nodules on the one hand and healthy thyroid tissue (p = 0.0019) or benign thyroid nodules (p = 0.0039) on the other hand. No significant difference of diagnostic accuracy for the diagnosis of malignant thyroid nodules was found between RTE and ARFI-imaging (0.74 vs. 0.69, p = 0.54). The combination of RTE with ARFI did not improve diagnostic accuracy.
Conclusions: ARFI can be used as an additional tool in the diagnostic work up of thyroid nodules with high negative predictive value and comparable results to RTE.
Using a microscopic transport model we investigate the evolution of conical structures originating from the supersonic projectile moving through the hot matter of ultrarelativistic particles. Using different scenarios for the interaction between projectile and matter, and different transport properties of the matter, we study the formation and structure of Mach cones. Especially, a dependence of the Mach cone angle on the details and rate of the energy deposition from projectile to the matter is investigated. Furthermore, the two-particle correlations extracted from the numerical calculations are compared to an analytical approximation. We find that the propagation of a high energetic particle through the matter does not lead to the appearance of a double peak structure as observed in the ultrarelativistic heavy-ion collision experiments. The reason is the strongly forward-peaked energy and momentum deposition in the head shock region. In addition, by adjusting the cross section we investigate the influence of the viscosity to the structure of Mach cones. A clear and unavoidable smearing of the profile depending on a finite ratio of shear viscosity to entropy density is clearly visible.
The dispreference for subject case ellipsis in OSV sentences has been analyzed as resulting from a violation of a structural requirement on the position of bare subject NPs (Ahn and Cho 2006a, 2006b, 2007). In this study, we present evidence from an acceptability rating experiment demonstrating that OSV sentences containing a case-ellipsed subject exhibit acceptability patterns different from ungrammatical sentences violating a core syntactic principle on case assignment and that these sentences are judged acceptable when the subject refers to expected, predictable information in context. This evidence supports the conclusion that the dispreference for subject case ellipsis in OSV sentences is due to violations of probabilistic constraints that favor case marking for rare types of subjects and such violations can be remedied by non-syntactic information.
Chung (2001) claims that non-final conjuncts without overt tense morphemes which produce asymmetric tense interpretations are to be analyzed as TP; and Lee (2005) argues that the verbal honorific affix -si- never occurs in non-final conjuncts so honorific agreement between the subject and the verb takes place in the final conjunct only and thus the Korean gapping constructions should be analyzed as vP coordination. However, these two previous analyses seem to fail to make the generalizations on the distributional behaviors of gapping constructions, facing theoretical and empirical difficulties. To solve the problems they face, we claim that verbal gapping in Korean is allowed to occur in all non-final conjuncts when the covert predicates of the non-final conjuncts have an identical semantic relation value with that of the overt verb in the final conjunct, regardless of the consistency of the honorific and tense values between conjuncts.
Predicative complements canonically show number and/or gender agreement with their target. The most detailed proposal on how to model it in HPSG is provided in Kathol (1999). This proposal, though, chiefly deals with the predicative adjectives of the Romance languages, and turns out to be inappropriate for dealing with predicate nominals. There is an obvious way to repair it, but it cannot be fitted in the canonical HPSG treatment of clauses with a predicative complement. It can be fitted, though, in a treatment of such clauses that was proposed in Van Eynde (2009). Adopting that treatment, the agreement is modeled in terms of a constraint on the lexemes which select a predicative complement.
Verb production in stroke induced aphasia and semantic dementia: similarities and dissociations
(2012)
The Japanese infinitive-clause construction (InfCx) and gerund-clause construction (GerCx), which are the most basic subordination structures (considered as coordination structures by some) in the language, may convey a wide range of interclausal semantic relations, including 'temporal sequence', 'cause', and 'manner', largely due to pragmatic enrichment. This work addresses the question of what the core meaning(s) of the two constructions is (are), and demonstrates (i) that the InfCx and GerCx indicate either that the first-clause eventuality precedes or temporally subsumes the second-clause eventuality or that the two clauses stand in the rhetorical relation of contrast, and (ii) that the GerCx has a distinct sense that the InfCx lacks, which gives rise to the 'resulting state' interpretation.
Comparison of the ellipsis-based theory of non-constituent coordination with its alternatives
(2012)
In this paper, I compare the ellipsis-based theory of non-constituent coordination proposed in Yatabe (2001) with three of its alternatives, namely the theory that has been widely accepted within the context of Categorial Grammar, Mouret's HPSG-based theory, and the theory proposed by Bachrach and Katzir in the framework of the Minimalist Program. It is found (i) that the CG-based theory of non-constituent coordination cannot deal with medial RNR, i.e. a subset of right-node raising constructions in which either all or a part of the right-node-raised material is realized at a location other than the right edge of the final conjunct, (ii) that Mouret's theory encounters similar difficulties when applied to RNR, and (iii) that Bachrach and Katzir's theory cannot be applied to left-node raising in English, has difficulty capturing the semantic inertness of medial RNR, and overgenerates in several ways. The ellipsis-based theory, on the other hand, appears to be consistent with all the observations.
We present, in the framework of the interacting hadron resonance gas, an evaluation of thermodynamical quantities. The interaction is modelled via a correction for the finite size of the hadrons. We investigate the sensitivity of the model calculations on the radius of the hadrons, which is a parameter of the model. Our calculations for thermodynamical quantities as energy and entropy densities and pressure are confronted with predictions using the lattice Quantum Chromodynamics (QCD) formalism.
Korean has two types of answers shorter than full sentential answers: Fragments and null argument constructions. Apparently the two constructions have the same interpretative processes. However, there are some cases where the fragment and null argument construction behave differently: e.g., wh-puzzles, sloppy interpretation. We suggest that the two constructions involve two different types of anaphora and that the sources of sloppy(-like) interpretation are fundamentally distinct. Fragments pattern differently with null arguments in that only the former may display genuine sloppy readings. The latter may yield sloppy-like readings which are pragmatically induced by the explicature that can be cancelled unlike genuine sloppy readings in fragments. Evidence (wh-ellipsis, quantifier ellipsis) all lends substantial support to our claim that fragments are analyzed as an instance of clausal ellipsis while null arguments are analyzed as an instance of null pronoun pro; hence, the former is surface anaphora whereas the latter is deep anaphora in the sense of Hankamer & Sag (1976).
The status of the analysis of electron-positron pairs measured by ALICE in pp collisions at √s = 7 TeV and central Pb-Pb collisions at √sNN = 2.76 TeV is presented. Key questions and the main challenges of the analysis are discussed on the basis of first raw invariant mass spectra for both collision systems.
The first measurement of neutron emission in electromagnetic dissociation of 208Pb nuclei at the LHC is presented. The measurement is performed using the neutron Zero Degree Calorimeters of the ALICE experiment, which detect neutral particles close to beam rapidity. The measured cross sections of single and mutual electromagnetic dissociation of Pb nuclei at sNN−−−√ = 2.76 TeV with neutron emission are σsingle EMD=187.4±0.2 (stat.) +13.2−11.2 (syst.) b and σmutual EMD=5.7±0.1 (stat.) ±0.4 (syst.) b, respectively. The experimental results are compared to the predictions from a relativistic electromagnetic dissociation model.
Suppression of high transverse momentum D mesons in central Pb-Pb collisions at √sNN = 2.76 TeV
(2012)
The production of the prompt charm mesons D0, D+, D∗+, and their antiparticles, was measured with the ALICE detector in Pb-Pb collisions at the LHC, at a centre-of-mass energy sNN−−−−√=2.76 TeV per nucleon--nucleon collision. The pT-differential production yields in the range 2<pT<16 GeV/c at central rapidity, |y|<0.5, were used to calculate the nuclear modification factor RAA with respect to a proton-proton reference obtained from the cross section measured at s√=7 TeV and scaled to s√=2.76 TeV. For the three meson species, RAA shows a suppression by a factor 3-4, for transverse momenta larger than 5 GeV/c in the 20% most central collisions. The suppression is reduced for peripheral collisions.
The ALICE experiment has measured the inclusive J/ψ production in Pb-Pb collisions at sNN−−−√=2.76 TeV down to zero transverse momentum in the rapidity range 2.5<y<4. A suppression of the inclusive J/ψ yield in Pb-Pb is observed with respect to the one measured in pp collisions scaled by the number of binary nucleon-nucleon collisions. The nuclear modification factor, integrated over the 0-80% most central collisions, is 0.545±0.032(stat.)±0.083(syst.) and does not exhibit a significant dependence on the collision centrality. These features appear significantly different from measurements at lower collision energies. Models including J/ψ production from charm quarks in a deconfined partonic phase can describe our data.
The ALICE experiment has measured the inclusive J/psi production in Pb-Pb collisions at sqrt(sNN) = 2.76 TeV down to zero transverse momentum in the rapidity range 2.5 < y < 4. A suppression of the inclusive J/psi yield in Pb-Pb is observed with respect to the one measured in pp collisions scaled by the number of binary nucleon-nucleon collisions. The nuclear modification factor, integrated over the 0%-80% most central collisions, is 0.545+/-0.032(stat)+/-0.083(syst) and does not exhibit a significant dependence on the collision centrality. These features appear significantly different from measurements at lower collision energies. Models including J/psi production from charm quarks in a deconfined partonic phase can describe our data.
The ALICE experiment has measured the inclusive J/psi production in Pb-Pb collisions at sqrt(sNN) = 2.76 TeV down to pt = 0 in the rapidity range 2.5 < y < 4. A suppression of the inclusive J/psi yield in Pb-Pb is observed with respect to the one measured in pp collisions scaled by the number of binary nucleon-nucleon collisions. The nuclear modification factor, integrated over the 0%-80% most central collisions, is 0.545 +/- 0.032 (stat.) +/- 0.084 (syst.) and does not exhibit a significant dependence on the collision centrality. These features appear significantly different from lower energy measurements. Models including J/psi production from charm quarks in a deconfined partonic phase can describe our data.
The production of K∗(892)0 and ϕ(1020) in pp collisions at s√=7 TeV was measured by the ALICE experiment at the LHC. The yields and the transverse momentum spectra d2N/dydpT at midrapidity |y|<0.5 in the range 0<pT<6 GeV/c for K∗(892)0 and 0.4<pT<6 GeV/c for ϕ(1020) are reported and compared to model predictions. Using the yield of pions, kaons, and Omega baryons measured previously by ALICE at s√=7 TeV, the ratios K∗/K−, ϕ/K∗, ϕ/K−, ϕ/π−, and (Ω + Ω¯¯¯¯)/ϕ are presented. The values of the K∗/K−, ϕ/K∗ and ϕ/K− ratios are similar to those found at lower centre-of-mass energies. In contrast, the ϕ/π− ratio, which has been observed to increase with energy, seems to saturate above 200 GeV. The (Ω + Ω¯¯¯¯)/ϕ ratio in the pT range 1-5 GeV/c is found to be in good agreement with the prediction of the HIJING/BB v2.0 model with a strong colour field.
In this Letter we report the first results on π±, K±, p and pp¯¯¯ production at mid-rapidity (|y|<0.5) in central Pb-Pb collisions at sNN−−−√ = 2.76 TeV, measured by the ALICE experiment at the LHC. The pT distributions and yields are compared to previous results at sNN−−−√ = 200 GeV and expectations from hydrodynamic and thermal models. The spectral shapes indicate a strong increase of the radial flow velocity with sNN−−−√, which in hydrodynamic models is expected as a consequence of the increasing particle density. While the K/π ratio is in line with predictions from the thermal model, the p/π ratio is found to be lower by a factor of about 1.5. This deviation from thermal model expectations is still to be understood.
The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at sqrt{s}=7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L_int = 5.6nb-1. The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p_t>1.3 GeV/c and rapidity |y|<0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the Psi(2S) and Csi_c resonances, is sigma_prompt-J/psi(pt > 1.3 GeV/c, |y| < 0.9) = 8.3 +- 0.8(stat.) +- 1.1(syst.) + 1.5 - 1.4(syst. pol.) micro barn. The cross section for the production of b-hadrons decaying to J/psi with p_t>1.3 GeV/c and |y|<0.9 is sigma_{J/psi<-h_B} = 1.46 +- 0.38(stat.) + 0.26 -0.32(syst.) micro barn. The results are compared to QCD model predictions. The shape of the p_t and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b-bbar pair total cross section and dsigma/dy at mid-rapidity.
The ALICE Collaboration has measured the inclusive production of muons from heavy flavour decays at forward rapidity, 2.5 < y < 4, in pp and Pb-Pb collisions at sNN−−−−√ = 2.76 TeV. The pT-differential inclusive cross section of muons from heavy flavour decays in pp collisions is compared to perturbative QCD calculations. The nuclear modification factor is studied as a function of pt and collision centrality. A weak suppression is measured in peripheral collisions. In the most central collisions, a suppression of a factor of about 3-4 is observed in 6 < pT < 10 GeV/c. The suppression shows no significant pT dependence.
Measurement of electrons from semileptonic heavy-flavor hadron decays in pp collisions at √s = 7 TeV
(2012)
The differential production cross section of electrons from semileptonic heavy-flavour hadron decays has been measured at mid-rapidity (|y|<0.5) in proton-proton collisions at s√=7 TeV with ALICE at the LHC. Electrons were measured in the transverse momentum range 0.5 <pT< 8 GeV/c. Predictions from a fixed order perturbative QCD calculation with next-to-leading-log resummation agree with the data within the theoretical and experimental uncertainties.
Measurement of charm production at central rapidity in proton-proton collisions at √s = 2.76 TeV
(2012)
The pT-differential production cross sections of the prompt (B feed-down subtracted) charmed mesons D0, D+, and D∗+ in the rapidity range |y|<0.5, and for transverse momentum 1<pT<12 GeV/c, were measured in proton-proton collisions at s√=2.76 TeV with the ALICE detector at the Large Hadron Collider. The analysis exploited the hadronic decays D0→Kπ, D+→Kππ, D∗+→D0π, and their charge conjugates, and was performed on a Lint=1.1 nb−1 event sample collected in 2011 with a minimum-bias trigger. The total charm production cross section at s√=2.76 TeV and at 7 TeV was evaluated by extrapolating to the full phase space the pT-differential production cross sections at s√=2.76 TeV and our previous measurements at s√=7 TeV. The results were compared to existing measurements and to perturbative-QCD calculations. The fraction of cdbar D mesons produced in a vector state was also determined.
This paper, in the context of multilingual MT, proposes the use of ICONS (Individual CONstraintS) to add a representation of information structure to MRS. The value of ICONS is a list of objects of type info-str, each of which has the features CLAUSE and TARGET. The subtypes of info-str indicate which information structural role is played by the TARGET with respect to the CLAUSE. This proposal is designed to support both the calculation of focus projection from underspecified representations and the handling of multiclausal sentences.
A simple and fast method of lipid analysis of isolated intact mitochondria by means of MALDI-TOF mass spectrometry is described. Mitochondria isolated from bovine heart and yeast have been employed to set up and validate the new method of lipid analysis. The mitochondrial suspension is directly applied over the target and, after drying, covered by a thin layer of the 9-aminoacridine matrix solution. The lipid profiles acquired with this procedure contain all peaks previously obtained by analyzing the lipid extracts of isolated mitochondria by TLC and/or mass spectrometry. The novel procedure allows the quick, simple, precise, and accurate analysis of membrane lipids, utilizing only a tiny amount of isolated organelle; it has also been tested with intact membranes of the bacterium Paracoccus denitrificans for its evolutionary link to present-day mitochondria. The method is of general validity for the lipid analysis of other cell fractions and isolated organelles.
An exciting in vivo function of ATP-sensitive potassium channels in substantia nigra dopamine neurons Ð Implications for burst firing and novelty coding ÐPhasic burst activity is a key feature of dopamine (DA) midbrain neurons. This particular pattern of excitation of DA neurons occurs via a synaptically triggered transition from low-frequency background spiking to transient high-frequency discharges. Burst-firing mediated phasic DA release is critical for flexible switching of behavioural strategies in response to unexpected rewards, novelty and other salient stimuli. However, the cellular and molecular bases of burst signalling in distinct DA subpopulations of the substantia nigra (SN) or the ventral tegmental area (VTA) are unknown.
DA neuron excitability is controlled by synaptic network inputs, neurotransmitter receptors and ion channels, which generate action potentials and determine frequency and pattern of electrical activity in a complex interplay. ATP-sensitive potassium (K-ATP) channels are widely expressed throughout the brain, where in most cases they are believed to act as metabolically-controlled 'excitation brakes' by matching excitability to cellular energy states. However, their precise physiological in vivo function in DA neurons remains elusive.
To study burst firing and the underlying ionic mechanisms with single cell resolution, in vivo single-unit recordings were combined with juxtacellular neurobiotin labelling as well as immunohistochemical and anatomical identification of individual DA neurons. In vivo recordings were performed in adult isoflurane-anaesthetised wildtype (WT) and global K-ATP channel knockout mice, lacking the pore forming Kir6.2 subunit (Kir6.2-/-). In addition, DA cell-selective functional silencing of K-ATP channel activity in vivo was established using virus-mediated expression of dominant-negative Kir6.2 subunits. Careful control experiments ruled out any significant contributions from nonDA neurons as transduction was effectively limited to SN DA neurons rather than affecting those cells that innervate them. Virus-based K-ATP channel silencing in combination with juxtacellular recording and labelling was achieved to define the electrophysiological phenotype of individually identified, virally-transduced DA neurons in vivo.
Single-unit recordings revealed that K-ATP channels Ð in contrast to their conventional hyperpolarising role Ð in a subpopulation of DA neurons located in the medial SN (m-SN) act as cell-type selective gates for excitatory burst firing in vivo. The percentage of spikes in bursts was threefold reduced in Kir6.2-/- compared to WT mice. Classification of firing patterns based on visual inspection of autocorrelation histograms and on a newly developed spike-train-model confirmed the dramatic shift from phasic burst to tonic single-spike oscillatory firing in Kir6.2-/-. This significant decrease of burstiness was selective for m-SN DA neurons and was not exhibited by DA cells in the lateral SN or VTA. Virus-based K-ATP channel silencing in vivo unequivocally demonstrated that the activity of postsynaptic K-ATP channels was sufficient to disrupt bursting in m-SN DA neuron subtypes. Patch-clamp recordings in brain slices indicated an essential role of K-ATP channels for NMDA-mediated in vitro bursting. In accordance with previous studies in DA midbrain neurons, NMDA receptor stimulation triggered burst-like firing in m-SN DA cells in vitro, but only when K-ATP channels were co-activated in these neurons.
K-ATP channel-gated burst firing in m-SN DA neurons might be functionally relevant in awake, freely moving mice. To explore the behavioural consequences of SN DA neuron subtype-selective K-ATP channel suppression, spontaneous open field (OF) behaviour of mice with bilateral K-ATP silencing across the whole SN (medial + lateral) or in only the lateral SN was tested. Analysis of WT and global Kir6.2-/- mice showed reduced exploratory locomotor activity of Kir6.2-/- in a novel OF environment. Remarkably, K-ATP channel silencing in m-SN DA neurons phenocopied this novelty-exploration deficit, indicating that K-ATP channel-gated burst firing in medial but not lateral SN DA neurons is crucial for WT-like novelty-dependent exploratory behaviour.
In summary, a novel role of K-ATP channels in promoting the excitatory switch from tonic to phasic firing in vivo in a cell-type specific manner was discovered. The present PhD thesis provides several important insights into the pivotal function of K-ATP channels in medial SN DA cells, which project to the dorsomedial striatum, for burst firing and its important consequences for context-dependent exploratory behaviour.
In collaboration with two other research groups transcriptional up-regulation of K-ATP channel and NMDA receptor subunits and high levels of in vivo burst firing were detected in surviving SN DA neurons from Parkinson's disease (PD) patients Ð providing a potential link of K-ATP channel activity to neurodegenerative pathomechanisms of PD. Using high-resolution fMRI imaging another study in humans has recently identified distinct DA midbrain regions that are preferentially activated by either reward or novelty. Taken together, these human data and the results of the present PhD thesis suggest that burst-gating K-ATP channel function in SN DA neurons impacts on phenotypes in disease as well as in health.
The midbrain DA system comprising dopamine (DA) neurons of the substantia nigra (SN) and the ventral tegmental area (VTA) is involved in various brain functions, including voluntary movement and the encoding and prediction of behaviorally relevant stimuli. In Parkinsonʼs disease (PD), a progressive degeneration of particularly vulnerable SN DA neurons causes a progressive DA depletion of striatal projection sites. As a consequence, motor symptoms such as tremor, hypokinesia and rigidity appear once about 50 % to 70 % of SN DA neurons have been lost. Under physiological conditions, SN DA neurons can encode behaviorally salient events and coordinated movements through tonic and phasic activity and correlated striatal DA release. Burst-activity mediates a phasic, supralinear rise of striatal DA levels and allows to activate coordinated movements via modulation of corticostriatal signals.
In the present dissertation project, pathophysiological adaptations of surviving SN DA neurons after a partial degeneration of the nigrostiatal system have been studied using a 6-hydroxydopamine mouse model of PD. Combining in vivo retrograde tracing techniques with in vitro whole-cell patch-clamp recordings, multifluorescent immunolabeling and confocal microscopy allowed an unambiguous correlation of electrophysiological phenotypes, anatomical positions and neurochemical phenotypes of recorded neurons on a single-cell level. In vitro, neuronal activity of SN DA neurons is characterized by spontaneous, slow pacemaker activity of 1 to 10 Hz and a high degree of spike-timing precision. In vitro current-clamp recordings of surviving SN DA neurons using acute brain slice preparations after a partial, PD-like degeneration of the nigrostriatal DA system showed a significant perturbation of spontaneous pacemaker activity, mirrored by a decreased spike-timing precision compared to controls. Selective pharmacology and whole-cell voltage-clamp recordings served to identify calciumactivated SK channels as molecular effectors of a perturbated pacemaker activity of surviving SN DA neurons. SK channels and have been shown to critically contribute to the spike-timing precision of SN DA neurons. Consistently, in vitro current-clamp recordings after pharmacological blockade of SK channels in vitro caused a significant decrease of spike-timing precision, occluding previously observed differences between surviving SN DA neurons and controls.In addition to in vitro patch-clamp recordings, extracellular single-unit recordings in anaesthetized animals in vivo served to study surviving SN DA neurons embedded in an intact neuronal network after a partial, PD-like degeneration of the nigrostriatal DA system. Combining in vivo single-unit recordings, juxtacellular neurobiotin labeling and multifluorescent immunohistochemistry allowed to directly correlate electrophysiological and neurochemical phenotypes as well as anatomical positions on a single-cell level. In vivo, surviving SN DA neurons showed a significant decrease of spike-timing precision as reflected by an increased irregularity and an augmented burst activity compared to controls.
The present dissertation project provided a unique combination of a neurotoxicological PD mouse model, retrograde tracing techniques and in vitro as well as in vivo electrophysiologiy, allowing to unambiguously correlate electrophysiological adaptations, projection-specific anatomical positions and neurochemical phenotypes of SN DA neurons after a partial degeneration of the nigrostriatal system. Surviving SN DA neurons exhibited a significant deficit of SK channel activity after a partial degeneration of the nigrostriatal DA system. In consequence of a diminished SK channel activity observed in vitro, surviving SN DA neurons exhibited and enhanced burst activity in vivo, providing a plausible mechanism to compensate a striatal DA depletion.
Speech production involves widely distributed brain regions. This MEG study focuses on the spectro-temporal dynamics that contribute to the setup of this network. In 21 participants performing a cue-target reading paradigm, we analyzed local oscillations during preparation for overt and covert reading in the time-frequency domain and localized sources using beamforming. Network dynamics were studied by comparing different dynamic causal models of beta phase coupling in and between hemispheres. While a broadband low frequency effect was found for any task preparation in bilateral prefrontal cortices, preparation for overt speech production was specifically associated with left-lateralized alpha and beta suppression in temporal cortices and beta suppression in motor-related brain regions. Beta phase coupling in the entire speech production network was modulated by anticipation of overt reading. We propose that the processes underlying the setup of the speech production network connect relevant brain regions by means of beta synchronization and prepare the network for left-lateralized information routing by suppression of inhibitory alpha and beta oscillations.
Background: Repetitive transcranial magnetic stimulation (rTMS) allows non-invasive stimulation of the human brain. However, no suitable marker has yet been established to monitor the immediate rTMS effects on cortical areas in children.
Objective: TMS-evoked EEG potentials (TEPs) could present a well-suited marker for real-time monitoring. Monitoring is particularly important in children where only few data about rTMS effects and safety are currently available.
Methods: In a single-blind sham-controlled study, twenty-five school-aged children with ADHD received subthreshold 1 Hz-rTMS to the primary motor cortex. The TMS-evoked N100 was measured by 64-channel-EEG pre, during and post rTMS, and compared to sham stimulation as an intraindividual control condition.
Results: TMS-evoked N100 amplitude decreased during 1 Hz-rTMS and, at the group level, reached a stable plateau after approximately 500 pulses. N100 amplitude to supra-threshold single pulses post rTMS confirmed the amplitude reduction in comparison to the pre-rTMS level while sham stimulation had no influence. EEG source analysis indicated that the TMS-evoked N100 change reflected rTMS effects in the stimulated motor cortex. Amplitude changes in TMS-evoked N100 and MEPs (pre versus post 1 Hz-rTMS) correlated significantly, but this correlation was also found for pre versus post sham stimulation.
Conclusion: The TMS-evoked N100 represents a promising candidate marker to monitor rTMS effects on cortical excitability in children with ADHD. TMS-evoked N100 can be employed to monitor real-time effects of TMS for subthreshold intensities. Though TMS-evoked N100 was a more sensitive parameter for rTMS-specific changes than MEPs in our sample, further studies are necessary to demonstrate whether clinical rTMS effects can be predicted from rTMS-induced changes in TMS-evoked N100 amplitude and to clarify the relationship between rTMS-induced changes in TMS-evoked N100 and MEP amplitudes. The TMS-evoked N100 amplitude reduction after 1 Hz-rTMS could either reflect a globally decreased cortical response to the TMS pulse or a specific decrease in inhibition.
Denervation-induced changes in excitatory synaptic strength were studied following entorhinal deafferentation of hippocampal granule cells in mature (≥3 weeks old) mouse organotypic entorhino-hippocampal slice cultures. Whole-cell patch-clamp recordings revealed an increase in excitatory synaptic strength in response to denervation during the first week after denervation. By the end of the second week synaptic strength had returned to baseline. Because these adaptations occurred in response to the loss of excitatory afferents, they appeared to be in line with a homeostatic adjustment of excitatory synaptic strength. To test whether denervation-induced changes in synaptic strength exploit similar mechanisms as homeostatic synaptic scaling following pharmacological activity blockade, we treated denervated cultures at 2 days post lesion for 2 days with tetrodotoxin. In these cultures, the effects of denervation and activity blockade were not additive, suggesting that similar mechanisms are involved. Finally, we investigated whether entorhinal denervation, which removes afferents from the distal dendrites of granule cells while leaving the associational afferents to the proximal dendrites of granule cells intact, results in a global or a local up-scaling of granule cell synapses. By using computational modeling and local electrical stimulations in Strontium (Sr2+)-containing bath solution, we found evidence for a lamina-specific increase in excitatory synaptic strength in the denervated outer molecular layer at 3–4 days post lesion. Taken together, our data show that entorhinal denervation results in homeostatic functional changes of excitatory postsynapses of denervated dentate granule cells in vitro.
The forward muon spectrometer of ALICE (A Large Ion Collider Experiment) is equipped with a trigger system made of four planes of Resistive Plate Chambers (RPC), arranged in two stations with two planes each, for a total area of about 140 m2. The system provides single and di-muon triggers with suitable transverse momentum selection, optimised for the physics of quarkonia and open heavy flavour. In the first two years of data-taking at the Large Hadron Collider (2010 and 2011) the 72 RPCs were operated in highly saturated avalanche mode in both pp and Pb-Pb collisions. The integrated charge was about 1.3 mC/cm2 on average and 3.5 mC/cm2 for the most exposed detectors. This paper describes two main results. The first result is the determination of the RPC performance, with particular focus on the stability of the main detector parameters such as efficiency, dark current, and dark rate. The second result is the measurement of the muon trigger performance in Pb-Pb collisions at √sNN = 2.76 TeV, in terms of the reliability and stability of the trigger decision logic.