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Institute
The second (v2) and third (v3) flow harmonic coefficients of J/ψ mesons are measured at forward rapidity (2.5 < y < 4.0) in Pb-Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the LHC. Results are obtained with the scalar product method and reported as a function of transverse momentum, pT, for various collision centralities. A positive value of J/ψ v3 is observed with 3.7σ significance. The measurements, compared to those of prompt D0 mesons and charged particles at mid-rapidity, indicate an ordering with vn(J/ψ) < vn(D0) < vn(h±) (n = 2, 3) at low and intermediate pT up to 6 GeV/c and a convergence with v2(J/ψ) ≈ v2(D0) ≈ v2(h±) at high pT above 6–8 GeV/c. In semi-central collisions (5–40% and 10–50% centrality intervals) at intermediate pT between 2 and 6 GeV/c, the ratio v3/v2 of J/ψ mesons is found to be significantly lower (4.6σ) with respect to that of charged particles. In addition, the comparison to the prompt D0-meson ratio in the same pT interval suggests an ordering similar to that of the v2 and v3 coefficients. The J/ψ v2 coefficient is further studied using the Event Shape Engineering technique. The obtained results are found to be compatible with the expected variations of the eccentricity of the initial-state geometry.
This paper compares measurements of gaseous and particulate emissions from a wide range of biomass-burning plumes intercepted by the NASA DC-8 research aircraft during the three phases of the ARCTAS-2008 experiment: ARCTAS-A, based out of Fairbanks, Alaska USA (3 April to 19 April 2008); ARCTAS-B based out of Cold Lake, Alberta, Canada (29 June to 13 July 2008); and ARCTAS-CARB, based out of Palmdale, California, USA (18 June to 24 June 2008). Extensive investigations of boreal fire plume evolution were undertaken during ARCTAS-B, where four distinct fire plumes that were intercepted by the aircraft over a range of down-wind distances (0.1 to 16 hr transport times) were studied in detail. Based on these analyses, there was no evidence for ozone production and a box model simulation of the data confirmed that net ozone production was slow (on average 1 ppbv h−1 in the first 3 h and much lower afterwards) due to limited NOx. Peroxyacetyl nitrate concentrations (PAN) increased with plume age and the box model estimated an average production rate of ~80 pptv h−1 in the first 3 h. Like ozone, there was also no evidence for net secondary inorganic or organic aerosol formation. There was no apparent increase in aerosol mass concentrations in the boreal fire plumes due to secondary organic aerosol (SOA) formation; however, there were indications of chemical processing of the organic aerosols. In addition to the detailed studies of boreal fire plume evolution, about 500 smoke plumes intercepted by the NASA DC-8 aircraft were segregated by fire source region. The normalized excess mixing ratios (i.e. ΔX/ΔCO) of gaseous (carbon dioxide, acetonitrile, hydrogen cyanide, toluene, benzene, methane, oxides of nitrogen (NOx), ozone, PAN) and fine aerosol particulate components (nitrate, sulfate, ammonium, chloride, organic aerosols and water soluble organic carbon) of these plumes were compared.
This paper compares measurements of gaseous and particulate emissions from a wide range of biomass-burning plumes intercepted by the NASA DC-8 research aircraft during the three phases of the ARCTAS-2008 experiment: ARCTAS-A, based out of Fairbanks, Alaska, USA (3 April to 19 April 2008); ARCTAS-B based out of Cold Lake, Alberta, Canada (29 June to 13 July 2008); and ARCTAS-CARB, based out of Palmdale, California, USA (18 June to 24 June 2008). Approximately 500 smoke plumes from biomass burning emissions that varied in age from minutes to days were segregated by fire source region and urban emission influences. The normalized excess mixing ratios (NEMR) of gaseous (carbon dioxide, acetonitrile, hydrogen cyanide, toluene, benzene, methane, oxides of nitrogen and ozone) and fine aerosol particulate components (nitrate, sulfate, ammonium, chloride, organic aerosols and water soluble organic carbon) of these plumes were compared. A detailed statistical analysis of the different plume categories for different gaseous and aerosol species is presented in this paper.
The comparison of NEMR values showed that CH4 concentrations were higher in air-masses that were influenced by urban emissions. Fresh biomass burning plumes mixed with urban emissions showed a higher degree of oxidative processing in comparison with fresh biomass burning only plumes. This was evident in higher concentrations of inorganic aerosol components such as sulfate, nitrate and ammonium, but not reflected in the organic components. Lower NOx NEMRs combined with high sulfate, nitrate and ammonium NEMRs in aerosols of plumes subject to long-range transport, when comparing all plume categories, provided evidence of advanced processing of these plumes.
Formalin‐fixed, paraffin‐embedded (FFPE ), biobanked tissue samples offer an invaluable resource for clinical and biomarker research. Here, we developed a pressure cycling technology (PCT )‐SWATH mass spectrometry workflow to analyze FFPE tissue proteomes and applied it to the stratification of prostate cancer (PC a) and diffuse large B‐cell lymphoma (DLBCL ) samples. We show that the proteome patterns of FFPE PC a tissue samples and their analogous fresh‐frozen (FF ) counterparts have a high degree of similarity and we confirmed multiple proteins consistently regulated in PC a tissues in an independent sample cohort. We further demonstrate temporal stability of proteome patterns from FFPE samples that were stored between 1 and 15 years in a biobank and show a high degree of the proteome pattern similarity between two types of histological regions in small FFPE samples, that is, punched tissue biopsies and thin tissue sections of micrometer thickness, despite the existence of a certain degree of biological variations. Applying the method to two independent DLBCL cohorts, we identified myeloperoxidase, a peroxidase enzyme, as a novel prognostic marker. In summary, this study presents a robust proteomic method to analyze bulk and biopsy FFPE tissues and reports the first systematic comparison of proteome maps generated from FFPE and FF samples. Our data demonstrate the practicality and superiority of FFPE over FF samples for proteome in biomarker discovery. Promising biomarker candidates for PC a and DLBCL have been discovered.
Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms.
Comprehensive results on the production of unidentified charged particles, π±, K±, K0S, K*(892)0, p, p¯¯¯, ϕ(1020), Λ, Λ¯¯¯¯, Ξ−, Ξ¯¯¯¯+, Ω− and Ω¯¯¯¯+ hadrons in proton-proton (pp) collisions at s√ = 7 TeV at midrapidity (|y|<0.5) as a function of charged-particle multiplicity density are presented. In order to avoid auto-correlation biases, the actual transverse momentum (pT) spectra of the particles under study and the event activity are measured in different rapidity windows. In the highest multiplicity class, the charged-particle density reaches about 3.5 times the value measured in inelastic collisions. While the yield of protons normalized to pions remains approximately constant as a function of multiplicity, the corresponding ratios of strange hadrons to pions show a significant enhancement that increases with increasing strangeness content. Furthermore, all identified particle to pion ratios are shown to depend solely on charged-particle multiplicity density, regardless of system type and collision energy. The evolution of the spectral shapes with multiplicity and hadron mass shows patterns that are similar to those observed in p-Pb and Pb-Pb collisions at LHC energies. The obtained pT distributions and yields are compared to expectations from QCD-based pp event generators as well as to predictions from thermal and hydrodynamic models. These comparisons indicate that traces of a collective, equilibrated system are already present in high-multiplicity pp collisions.
Comprehensive results on the production of unidentified charged particles, π±, K±, K0S, K*(892)0, p, p¯¯¯, ϕ(1020), Λ, Λ¯¯¯¯, Ξ−, Ξ¯¯¯¯+, Ω− and Ω¯¯¯¯+ hadrons in proton-proton (pp) collisions at s√ = 7 TeV at midrapidity (|y|<0.5) as a function of charged-particle multiplicity density are presented. In order to avoid auto-correlation biases, the actual transverse momentum (pT) spectra of the particles under study and the event activity are measured in different rapidity windows. In the highest multiplicity class, the charged-particle density reaches about 3.5 times the value measured in inelastic collisions. While the yield of protons normalized to pions remains approximately constant as a function of multiplicity, the corresponding ratios of strange hadrons to pions show a significant enhancement that increases with increasing strangeness content. Furthermore, all identified particle to pion ratios are shown to depend solely on charged-particle multiplicity density, regardless of system type and collision energy. The evolution of the spectral shapes with multiplicity and hadron mass shows patterns that are similar to those observed in p-Pb and Pb-Pb collisions at LHC energies. The obtained pT distributions and yields are compared to expectations from QCD-based pp event generators as well as to predictions from thermal and hydrodynamic models. These comparisons indicate that traces of a collective, equilibrated system are already present in high-multiplicity pp collisions.
Comprehensive results on the production of unidentified charged particles, π±, K±, K0S, K*(892)0, p, p¯¯¯, ϕ(1020), Λ, Λ¯¯¯¯, Ξ−, Ξ¯¯¯¯+, Ω− and Ω¯¯¯¯+ hadrons in proton-proton (pp) collisions at s√ = 7 TeV at midrapidity (|y|<0.5) as a function of charged-particle multiplicity density are presented. In order to avoid auto-correlation biases, the actual transverse momentum (pT) spectra of the particles under study and the event activity are measured in different rapidity windows. In the highest multiplicity class, the charged-particle density reaches about 3.5 times the value measured in inelastic collisions. While the yield of protons normalized to pions remains approximately constant as a function of multiplicity, the corresponding ratios of strange hadrons to pions show a significant enhancement that increases with increasing strangeness content. Furthermore, all identified particle to pion ratios are shown to depend solely on charged-particle multiplicity density, regardless of system type and collision energy. The evolution of the spectral shapes with multiplicity and hadron mass shows patterns that are similar to those observed in p-Pb and Pb-Pb collisions at LHC energies. The obtained pT distributions and yields are compared to expectations from QCD-based pp event generators as well as to predictions from thermal and hydrodynamic models. These comparisons indicate that traces of a collective, equilibrated system are already present in high-multiplicity pp collisions.
We present the first measurements of femtoscopic correlations between the K0S and K± particles in pp collisions at s√=7 TeV measured by the ALICE experiment. The observed femtoscopic correlations are consistent with final-state interactions proceeding solely via the a0(980) resonance. The extracted kaon source radius and correlation strength parameters for K0SK− are found to be equal within the experimental uncertainties to those for K0SK+. Results of the present study are compared with those from identical-kaon femtoscopic studies also performed with pp collisions at s√=7 TeV by ALICE and with a K0SK± measurement in Pb-Pb collisions at sNN−−−√=2.76 TeV. Combined with the Pb-Pb results, our pp analysis is found to be compatible with the interpretation of the a0(980) having a tetraquark structure instead of that of a diquark.
We present the first measurements of femtoscopic correlations between the K0S and K± particles in pp collisions at s√=7 TeV measured by the ALICE experiment. The observed femtoscopic correlations are consistent with final-state interactions proceeding solely via the a0(980) resonance. The extracted kaon source radius and correlation strength parameters for K0SK− are found to be equal within the experimental uncertainties to those for K0SK+. Results of the present study are compared with those from identical-kaon femtoscopic studies also performed with pp collisions at s√=7 TeV by ALICE and with a K0SK± measurement in Pb-Pb collisions at sNN−−−√=2.76 TeV. Combined with the Pb-Pb results, our pp analysis is found to be compatible with the interpretation of the a0(980) having a tetraquark structure instead of that of a diquark.
The second (v2) and third (v3) flow harmonic coefficients of J/ψ mesons are measured at forward rapidity (2.5 < y < 4.0) in Pb-Pb collisions at sNN−−−√ = 5.02 TeV with the ALICE detector at the LHC. Results are obtained with the scalar product method and reported as a function of transverse momentum, pT, for various collision centralities. A positive value of J/ψ v3 is observed with 3.7σ significance. The measurements, compared to those of prompt D0 mesons and charged particles at mid-rapidity, indicate an ordering with vn(J/ψ) <vn(D0) <vn(h±) (n = 2, 3) at low and intermediate pT up to 6 GeV/c and a convergence with v2(J/ψ) ≈v2(D0) ≈v2(h±) at high pT above 6-8 GeV/c. In semi-central collisions (5-40% and 10-50% centrality intervals) at intermediate pT between 2 and 6 GeV/c, the ratio v3/v2 of J/ψ mesons is found to be significantly lower (4.6σ) with respect to that of charged particles. In addition, the comparison to the prompt D0-meson ratio in the same pT interval suggests an ordering similar to that of the v2 and v3 coefficients. The J/ψ v2 coefficient is further studied using the Event Shape Engineering technique. The obtained results are found to be compatible with the expected variations of the eccentricity of the initial-state geometry.
The second (v2) and third (v3) flow harmonic coefficients of J/ψ mesons are measured at forward rapidity (2.5 < y < 4.0) in Pb-Pb collisions at sNN−−−√ = 5.02 TeV with the ALICE detector at the LHC. Results are obtained with the scalar product method and reported as a function of transverse momentum, pT, for various collision centralities. A positive value of J/ψ v3 is observed with 3.7σ significance. The measurements, compared to those of prompt D0 mesons and charged particles at mid-rapidity, indicate an ordering with vn(J/ψ) <vn(D0) <vn(h±) (n = 2, 3) at low and intermediate pT up to 6 GeV/c and a convergence with v2(J/ψ) ≈v2(D0) ≈v2(h±) at high pT above 6-8 GeV/c. In semi-central collisions (5-40% and 10-50% centrality intervals) at intermediate pT between 2 and 6 GeV/c, the ratio v3/v2 of J/ψ mesons is found to be significantly lower (4.6σ) with respect to that of charged particles. In addition, the comparison to the prompt D0-meson ratio in the same pT interval suggests an ordering similar to that of the v2 and v3 coefficients. The J/ψ v2 coefficient is further studied using the Event Shape Engineering technique. The obtained results are found to be compatible with the expected variations of the eccentricity of the initial-state geometry.
Two-particle correlations in high-energy collision experiments enable the extraction of particle source radii by using the Bose-Einstein enhancement of pion production at low relative momentum q∝1/R. It was previously observed that in pp collisions at s√=7 TeV the average pair transverse momentum kT range of such analyses is limited due to large background correlations which were attributed to mini-jet phenomena. To investigate this further, an event-shape dependent analysis of Bose-Einstein correlations for pion pairs is performed in this work. By categorizing the events by their transverse sphericity ST into spherical (ST>0.7) and jet-like (ST<0.3) events a method was developed that allows for the determination of source radii for much larger values of kT for the first time. Spherical events demonstrate little or no background correlations while jet-like events are dominated by them. This observation agrees with the hypothesis of a mini-jet origin of the non-femtoscopic background correlations and gives new insight into the physics interpretation of the kT dependence of the radii. The emission source size in spherical events shows a substantially diminished kT dependence, while jet-like events show indications of a negative trend with respect to kT in the highest multiplicity events. Regarding the emission source shape, the correlation functions for both event sphericity classes show good agreement with an exponential shape, rather than a Gaussian one.
Two-particle correlations in high-energy collision experiments enable the extraction of particle source radii by using the Bose-Einstein enhancement of pion production at low relative momentum q∝1/R. It was previously observed that in pp collisions at s√=7 TeV the average pair transverse momentum kT range of such analyses is limited due to large background correlations which were attributed to mini-jet phenomena. To investigate this further, an event-shape dependent analysis of Bose-Einstein correlations for pion pairs is performed in this work. By categorizing the events by their transverse sphericity ST into spherical (ST>0.7) and jet-like (ST<0.3) events a method was developed that allows for the determination of source radii for much larger values of kT for the first time. Spherical events demonstrate little or no background correlations while jet-like events are dominated by them. This observation agrees with the hypothesis of a mini-jet origin of the non-femtoscopic background correlations and gives new insight into the physics interpretation of the kT dependence of the radii. The emission source size in spherical events shows a substantially diminished kT dependence, while jet-like events show indications of a negative trend with respect to kT in the highest multiplicity events. Regarding the emission source shape, the correlation functions for both event sphericity classes show good agreement with an exponential shape, rather than a Gaussian one.
The ALICE Collaboration has measured the energy dependence of exclusive photoproduction of J/ψ vector mesons off proton targets in ultra-peripheral p-Pb collisions at a centre-of-mass energy per nucleon pair sNN−−−√=5.02 TeV. The e+e− and μ+μ− decay channels are used to measure the cross section as a function of the rapidity of the J/ψ in the range −2.5<y<2.7, corresponding to an energy in the γp centre-of-mass in the interval 40<Wγp<550 GeV. The measurements, which are consistent with a power law dependence of the exclusive J/ψ photoproduction cross section, are compared to previous results from HERA and the LHC and to several theoretical models. They are found to be compatible with previous measurements.
Event-shape engineering for the D-meson elliptic flow in mid-central Pb–Pb collisions at √sNN = 5.02
(2019)
The production yield of prompt D mesons and their elliptic flow coefficient v2 were measured with the Event-Shape Engineering (ESE) technique applied to mid-central (10-30% and 30-50% centrality classes) Pb-Pb collisions at the centre-of-mass energy per nucleon pair sNN−−−√=5.02 TeV, with the ALICE detector at the LHC. The ESE technique allows the classification of events, belonging to the same centrality, according to the azimuthal anisotropy of soft particle production in the collision. The reported measurements give the opportunity to investigate the dynamics of charm quarks in the Quark-Gluon Plasma and provide information on their participation in the collective expansion of the medium. D mesons were reconstructed via their hadronic decays at mid-rapidity, |η|<0.8, in the transverse momentum interval 1<pT<24 GeV/c. The v2 coefficient is found to be sensitive to the event-shape selection confirming a correlation between the D-meson azimuthal anisotropy and the collective expansion of the bulk matter, while the per-event D-meson yields do not show any significant modification within the current uncertainties.
The ALICE Collaboration has measured the energy dependence of exclusive photoproduction of J/ψ vector mesons off proton targets in ultra-peripheral p-Pb collisions at a centre-of-mass energy per nucleon pair sNN−−−√=5.02 TeV. The e+e− and μ+μ− decay channels are used to measure the cross section as a function of the rapidity of the J/ψ in the range −2.5<y<2.7, corresponding to an energy in the γp centre-of-mass in the interval 40<Wγp<550 GeV. The measurements, which are consistent with a power law dependence of the exclusive J/ψ photoproduction cross section, are compared to previous results from HERA and the LHC and to several theoretical models. They are found to be compatible with previous measurements.
A measurement of the production of prompt Λ+c baryons in Pb-Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the LHC is reported. The Λ+c and Λ¯¯¯¯−c were reconstructed at midrapidity (|y|<0.5) via the hadronic decay channel Λ+c→pK0S (and charge conjugate) in the transverse momentum and centrality intervals 6<pT<12 GeV/c and 0-80%. The Λ+c/D0 ratio, which is sensitive to the charm quark hadronisation mechanisms in the medium, is measured and found to be larger than the ratio measured in minimum-bias pp collisions at s√=7 TeV and in p-Pb collisions at sNN−−−√=5.02 TeV. In particular, the values in p-Pb and Pb-Pb collisions differ by about two standard deviations of the combined statistical and systematic uncertainties in the common pT interval covered by the measurements in the two collision system. The Λ+c/D0 ratio is also compared with model calculations including different implementations of charm quark hadronisation. The measured ratio is reproduced by models implementing a pure coalescence scenario, while adding a fragmentation contribution leads to an underestimation. The Λ+c nuclear modification factor, RAA, is also presented. The measured values of the RAA of Λ+c, Ds and non-strange D mesons are compatible within the combined statistical and systematic uncertainties. They show, however, a hint of a hierarchy (RD0AA<RDsAA<RΛ+cAA), conceivable with a contribution of recombination mechanisms to charm hadron formation in the medium.
Event-shape engineering for the D-meson elliptic flow in mid-central Pb–Pb collisions at √sNN = 5.02
(2018)
The production yield of prompt D mesons and their elliptic flow coefficient v2 were measured with the Event-Shape Engineering (ESE) technique applied to mid-central (10-30% and 30-50% centrality classes) Pb-Pb collisions at the centre-of-mass energy per nucleon pair sNN−−−√=5.02 TeV, with the ALICE detector at the LHC. The ESE technique allows the classification of events, belonging to the same centrality, according to the azimuthal anisotropy of soft particle production in the collision. The reported measurements give the opportunity to investigate the dynamics of charm quarks in the Quark-Gluon Plasma and provide information on their participation in the collective expansion of the medium. D mesons were reconstructed via their hadronic decays at mid-rapidity, |η|<0.8, in the transverse momentum interval 1<pT<24 GeV/c. The v2 coefficient is found to be sensitive to the event-shape selection confirming a correlation between the D-meson azimuthal anisotropy and the collective expansion of the bulk matter, while the per-event D-meson yields do not show any significant modification within the current uncertainties.
A measurement of the production of prompt Λ+c baryons in Pb-Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the LHC is reported. The Λ+c and Λ¯¯¯¯−c were reconstructed at midrapidity (|y|<0.5) via the hadronic decay channel Λ+c→pK0S (and charge conjugate) in the transverse momentum and centrality intervals 6<pT<12 GeV/c and 0-80%. The Λ+c/D0 ratio, which is sensitive to the charm quark hadronisation mechanisms in the medium, is measured and found to be larger than the ratio measured in minimum-bias pp collisions at s√=7 TeV and in p-Pb collisions at sNN−−−√=5.02 TeV. In particular, the values in p-Pb and Pb-Pb collisions differ by about two standard deviations of the combined statistical and systematic uncertainties. The Λ+c/D0 ratio is also compared with model calculations including different implementations of charm quark hadronisation. The measured ratio is reproduced by models implementing a pure coalescence scenario, while adding a fragmentation contribution leads to an underestimation. The Λ+c nuclear modification factor, RAA, is also presented. The measured values of the RAA of Λ+c, Ds and non-strange D mesons are compatible within the combined statistical and systematic uncertainties. They show, however, a hint of a hierarchy (RD0AA<RDsAA<RΛ+cAA), conceivable with a contribution of recombination mechanisms to charm hadron formation in the medium.
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
The Kinase Chemogenomic Set (KCGS): an open science resource for kinase vulnerability identification
(2021)
We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS), current Version 1.0, is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.
We present the first measurements of femtoscopic correlations between the K0 S and K± particles in pp collisions at √s = 7 TeV measured by the ALICE experiment. The observed femtoscopic correlations are consistent with final-state interactions proceeding solely via the a0(980) resonance. The extracted kaon source radius and correlation strength parameters for K0 SK− are found to be equal within the experimental uncertainties to those for K0 SK+. Results of the present study are compared with those from identical-kaon femtoscopic studies also performed with pp collisions at √s = 7 TeV by ALICE andwith a K0 SK± measurement in Pb–Pb collisions at √sNN = 2.76 TeV. Combined with the Pb–Pb results, our pp analysis is found to be compatible with th e interpretation of the a0(980) having a tetraquark structure instead of that of a diquark.
Clustering of cardiovascular risk factors and carotid intima-media thickness : the USE-IMT study
(2017)
Background: The relation of a single risk factor with atherosclerosis is established. Clinically we know of risk factor clustering within individuals. Yet, studies into the magnitude of the relation of risk factor clusters with atherosclerosis are limited. Here, we assessed that relation.
Methods: Individual participant data from 14 cohorts, involving 59,025 individuals were used in this cross-sectional analysis. We made 15 clusters of four risk factors (current smoking, overweight, elevated blood pressure, elevated total cholesterol). Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) between clusters using those without any of the four risk factors as reference group.
Results: Compared to the reference, those with 1, 2, 3 or 4 risk factors had a significantly higher common CIMT: mean difference of 0.026 mm, 0.052 mm, 0.074 mm and 0.114 mm, respectively. These findings were the same in men and in women, and across ethnic groups. Within each risk factor cluster (1, 2, 3 risk factors), groups with elevated blood pressure had the largest CIMT and those with elevated cholesterol the lowest CIMT, a pattern similar for men and women.
Conclusion: Clusters of risk factors relate to increased common CIMT in a graded manner, similar in men, women and across race-ethnic groups. Some clusters seemed more atherogenic than others. Our findings support the notion that cardiovascular prevention should focus on sets of risk factors rather than individual levels alone, but may prioritize within clusters.
Inhibitory interneurons govern virtually all computations in neocortical circuits and are in turn controlled by neuromodulation. While a detailed understanding of the distinct marker expression, physiology, and neuromodulator responses of different interneuron types exists for rodents and recent studies have highlighted the role of specific interneurons in converting rapid neuromodulatory signals into altered sensory processing during locomotion, attention, and associative learning, it remains little understood whether similar mechanisms exist in human neocortex. Here, we use whole-cell recordings combined with agonist application, transgenic mouse lines, in situ hybridization, and unbiased clustering to directly determine these features in human layer 1 interneurons (L1-INs). Our results indicate pronounced nicotinic recruitment of all L1-INs, whereas only a small subset co-expresses the ionotropic HTR3 receptor. In addition to human specializations, we observe two comparable physiologically and genetically distinct L1-IN types in both species, together indicating conserved rapid neuromodulation of human neocortical circuits through layer 1.
The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
The Kinase Chemogenomic Set (KCGS): An open science resource for kinase vulnerability identification
(2019)
We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS) is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.
Owing to their morphological complexity and dense network connections, neurons modify their proteomes locally, using mRNAs and ribosomes present in the neuropil (tissue enriched for dendrites and axons). Although ribosome biogenesis largely takes place in the nucleus and perinuclear region, neuronal ribosomal protein (RP) mRNAs have been frequently detected remotely, in dendrites and axons. Here, using imaging and ribosome profiling, we directly detected the RP mRNAs and their translation in the neuropil. Combining brief metabolic labeling with mass spectrometry, we found that a group of RPs rapidly associated with translating ribosomes in the cytoplasm and that this incorporation was independent of canonical ribosome biogenesis. Moreover, the incorporation probability of some RPs was regulated by location (neurites vs. cell bodies) and changes in the cellular environment (following oxidative stress). Our results suggest new mechanisms for the local activation, repair and/or specialization of the translational machinery within neuronal processes, potentially allowing neuronal synapses a rapid means to regulate local protein synthesis.
Owing to their morphological complexity and dense network connections, neurons modify their proteomes locally, using mRNAs and ribosomes present in the neuropil (tissue enriched for dendrites and axons). Although ribosome biogenesis largely takes place in the nucleus and perinuclear region, neuronal ribosomal protein (RP) mRNAs have been frequently detected remotely, in dendrites and axons. Here, using imaging and ribosome profiling, we directly detected the RP mRNAs and their translation in the neuropil. Combining brief metabolic labeling with mass spectrometry, we found that a group of RPs quickly associated with translating ribosomes in the cytoplasm and that this incorporation is independent of canonical ribosome biogenesis. Moreover, the incorporation probability of some RPs was regulated by location (neurites vs. cell bodies) and changes in the cellular environment (in response to oxidative stress). Our results suggest new mechanisms for the local activation, repair and/or specialization of the translational machinery within neuronal processes, potentially allowing remote neuronal synapses a rapid solution to the relatively slow and energy-demanding requirement of nuclear ribosome biogenesis.
We assessed the prognostic value of hypoxia (carbonic anhydrase 9; CA9), vessel density (CD31), with macrophages (CD68) and B cells (CD20) that can interact and lead to immune suppression and disease progression using scanning and histological mapping of whole-mount FFPE pancreatectomy tissue sections from 141 primarily resectable pancreatic ductal adenocarcinoma (PDAC) samples treated with surgery and adjuvant chemotherapy. Their expression was correlated with clinicopathological characteristics, and overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of stroma density (haematoxylin-eosin) and activity (alpha-smooth muscle actin). The median OS was 21 months after a mean follow-up of 20 months (range, 2–69 months). The median tumor surface area positive for CA9 and CD31 was 7.8% and 8.1%, respectively. Although total expression of these markers lacked prognostic value in the entire cohort, nevertheless, high tumor compartment CD68 expression correlated with worse PFS (p = 0.033) and DMFS (p = 0.047). Also, high CD31 expression predicted for worse OS (p = 0.004), PFS (p = 0.008), LPFS (p = 0.014) and DMFS (p = 0.004) in patients with moderate density stroma. High stromal and peripheral compartment CD68 expression predicted for significantly worse outcome in patients with loose and moderate stroma density, respectively. Altogether, in contrast to the current notion, hypoxia levels in PDAC appear to be comparable to other malignancies. CD31 and CD68 constitute prognostic markers in patient subgroups that vary according to tumor compartment and stromal density. Our study provides important insight on the pathophysiology of PDAC and should be exploited for future treatments.
An experiment addressing electron capture (EC) decay of hydrogen-like 142Pm60+ions has been conducted at the experimental storage ring (ESR) at GSI. The decay appears to be purely exponential and no modulations were observed. Decay times for about 9000 individual EC decays have been measured by applying the single-ion decay spectroscopy method. Both visually and automatically analysed data can be described by a single exponential decay with decay constants of 0.0126(7)s−1 for automatic analysis and 0.0141(7)s−1 for manual analysis. If a modulation superimposed on the exponential decay curve is assumed, the best fit gives a modulation amplitude of merely 0.019(15), which is compatible with zero and by 4.9 standard deviations smaller than in the original observation which had an amplitude of 0.23(4).