Characterization of the sources of protein-ligand affinity: 1-sulfonato-8-(1')anilinonaphthalene binding to intestinal fatty acid binding protein

1-Sulfonato-8-(1')anilinonaphthalene (1,8-ANS) was employed as a fluorescent probe of the fatty acid binding site of recombinant rat intestinal fatty acid binding protein (1-FABP). The enhancement of fluorescence upon binding allowed direct determination of binding affinity by fluorescence titration experiments, and measurement of the effects on that affinity of temperature, pH, and ionic strength. Solvent isotope effects were also determined. These data were compared to results from isothermal titration calorimetry. We obtained values for the enthalpy and entropy of this interaction at a variety of temperatures, and hence determined the change in heat capacity of the system consequent upon binding. The ANS-1-FABP is enthalpically driven; above approximately 14 degrees C it is entropically opposed, but below this temperature the entropy makes a positive contribution to the binding. The changes we observe in both enthalpy and entropy of binding with temperature can be derived from the change in heat capacity upon binding by integration, which demonstrates the internal consistency of our results. Bound ANS is displaced by fatty acids and can itself displace fatty acids bound to I-FABP. The binding site for ANS appears to be inside the solvent-containing cavity observed in the x-ray crystal structure, the same cavity occupied by fatty acid. From the fluorescence spectrum and from an inversion of the Debye-Hueckel formula for the activity coefficients as a function of added salt, we inferred that this cavity is fairly polar in character, which is in keeping with inferences drawn from the x-ray structure. The binding affinity of ANS is considered to be a consequence of both electrostatic and conditional hydrophobic effects. We speculate that the observed change in heat capacity is produced mainly by the displacement of strongly hydrogen-bonded waters from the protein cavity

Eureka and beyond: mining's impact on African urbanisation

This collection brings separate literatures on mining and urbanisation together at a time when both artisanal and large-scale mining are expanding in many African economies. While much has been written about contestation over land and mineral rights, the impact of mining on settlement, notably its catalytic and fluctuating effects on migration and urban growth, has been largely ignored. African nation-states’ urbanisation trends have shown considerable variation over the past half century. The current surge in ‘new’ mining countries and the slow-down in ‘old’ mining countries are generating some remarkable settlement patterns and welfare outcomes. Presently, the African continent is a laboratory of national mining experiences. This special issue on African mining and urbanisation encompasses a wide cross-section of country case studies: beginning with the historical experiences of mining in Southern Africa (South Africa, Zambia, Zimbabwe), followed by more recent mineralizing trends in comparatively new mineral-producing countries (Tanzania) and an established West African gold producer (Ghana), before turning to the influence of conflict minerals (Angola, the Democratic Republic of Congo and Sierra Leone)

Racial Differences in PAM50 Subtypes in the Carolina Breast Cancer Study

Background: African American breast cancer patients have lower frequency of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative disease and higher subtype-specific mortality. Racial differences in molecular subtype within clinically defined subgroups are not well understood. Methods: Using data and biospecimens from the population-based Carolina Breast Cancer Study (CBCS) Phase 3 (2008-2013), we classified 980 invasive breast cancers using RNA expression-based PAM50 subtype and recurrence (ROR) score that reflects proliferation and tumor size. Molecular subtypes (Luminal A, Luminal B, HER2-enriched, and Basal-like) and ROR scores (high vs low/medium) were compared by race (blacks vs whites) and age (≤50 years vs≥50 years) using chi-square tests and analysis of variance tests. Results: Black women of all ages had a statistically significantly lower frequency of Luminal A breast cancer (25.4% and 33.6% in blacks vs 42.8% and 52.1% in whites; younger and older, respectively). All other subtype frequencies were higher in black women (case-only odds ratio [OR] = 3.11, 95% confidence interval [CI] = 2.22 to 4.37, for Basal-like; OR=1.45, 95% CI=1.02 to 2.06, for Luminal B; OR=2.04, 95% CI=1.33 to 3.13, for HER2-enriched). Among clinically HR+/HER2- cases, Luminal A subtype was less common and ROR scores were statistically significantly higher among black women. Conclusions: Multigene assays highlight racial disparities in tumor subtype distribution that persist even in clinically defined subgroups. Differences in tumor biology (eg, HER2-enriched status) may be targetable to reduce disparities among clinically ER+/HER2- cases

Weber and church governance: religious practice and economic activity

The debate about the relationship between religion and economic activity in the wake of Weber has been cast largely in terms of belief and values. This article suggests an alternative focus on practice. It argues that taken for granted practices of church governance formed to-hand resources for the organization of economic activity. The argument is developed through an examination of the historical development of church governance practices in the Presbyterian Church of Scotland, with particular emphasis on the way in which theological belief gave rise to practices of accountability and record keeping. In turn such practices contributed to a ‘culture of organization’ which had implications for economic activity. A focus on governance practices can help to illuminate enduring patterns of difference in the organization of economic activity

A search for neutral Higgs bosons in the MSSM and models with two scalar field doublets

A search is described for the neutral Higgs bosons h^0 and A^0 predicted by models with two scalar field doublets and, in particular, the Minimal Supersymmetric Standard Model (MSSM). The search in the Z^0 h^0 and h^0 A^0 production channels is based on data corresponding to an integrated luminosity of 25 pb^{-1} from e^+e^- collisions at centre-of-mass energies between 130 and 172GeV collected with the OPAL detector at LEP. The observation of a number of candidates consistent with Standard Model background expectations is used in combination with earlier results from data collected at the Z^0 resonance to set limits on m_h and m_A in general models with two scalar field doublets and in the MSSM. For example, in the MSSM, for tan(beta) > 1, minimal and maximal scalar top quark mixing and soft SUSY-breaking masses of 1 TeV, the 95% confidence level limits m_h > 59.0 GeV and m_A > 59.5 GeV are obtained. For the first time, the MSSM parameter space is explored in a detailed scan.A search is described for the neutral Higgs bosons h^0 and A^0 predicted by models with two scalar field doublets and, in particular, the Minimal Supersymmetric Standard Model (MSSM). The search in the Z^0 h^0 and h^0 A^0 production channels is based on data corresponding to an integrated luminosity of 25 pb^{-1} from e^+e^- collisions at centre-of-mass energies between 130 and 172 GeV collected with the OPAL detector at LEP. The observation of a number of candidates consistent with Standard Model background expectations is used in combination with earlier results from data collected at the Z^0 resonance to set limits on m_h and m_A in general models with two scalar field doublets and in the MSSM. For example, in the MSSM, for tan(beta) > 1, minimal and maximal scalar top quark mixing and soft SUSY-breaking masses of 1 TeV, the 95% confidence level limits m_h > 59.0 GeV and m_A > 59.5 GeV are obtained. For the first time, the MSSM parameter space is explored in a detailed scan

Spin alignment of leading K∗(892)0K^{*}(892)^{0} mesons in hadronic Z0Z^0 decays

Helicity density matrix elements for inclusive K*(892)^0 mesons from hadronic Z^0 decays have been measured over the full range of K^*0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x_p values above 0.3, with the matrix element rho_00 rising to 0.66 +/- 0.11 for x_p > 0.7. The values of the real part of the off-diagonal element rho_1-1 are negative at large x_p, with a weighted average value of -0.09 +/- 0.03 for x_p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the qq(bar) system from the Z^0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x_p range. The K^*0 fragmentation function has also been measured and the total rate determined to be 0.74 +/- 0.02 +/- 0.02 K*(892)^0 mesons per hadronic Z^0 decay.Helicity density matrix elements for inclusive K*(892)^0 mesons from hadronic Z^0 decays have been measured over the full range of K^*0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x_p values above 0.3, with the matrix element rho_00 rising to 0.66 +/- 0.11 for x_p > 0.7. The values of the real part of the off-diagonal element rho_1-1 are negative at large x_p, with a weighted average value of -0.09 +/- 0.03 for x_p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the qq(bar) system from the Z^0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x_p range. The K^*0 fragmentation function has also been measured and the total rate determined to be 0.74 +/- 0.02 +/- 0.02 K*(892)^0 mesons per hadronic Z^0 decay.Helicity density matrix elements for inclusive K*(892)^0 mesons from hadronic Z^0 decays have been measured over the full range of K^*0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x_p values above 0.3, with the matrix element rho_00 rising to 0.66 +/- 0.11 for x_p > 0.7. The values of the real part of the off-diagonal element rho_1-1 are negative at large x_p, with a weighted average value of -0.09 +/- 0.03 for x_p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the qq(bar) system from the Z^0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x_p range. The K^*0 fragmentation function has also been measured and the total rate determined to be 0.74 +/- 0.02 +/- 0.02 K*(892)^0 mesons per hadronic Z^0 decay.Helicity density matrix elements for inclusive K*(892)^0 mesons from hadronic Z^0 decays have been measured over the full range of K^*0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x_p values above 0.3, with the matrix element rho_00 rising to 0.66 +/- 0.11 for x_p > 0.7. The values of the real part of the off-diagonal element rho_1-1 are negative at large x_p, with a weighted average value of -0.09 +/- 0.03 for x_p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the qq(bar) system from the Z^0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x_p range. The K^*0 fragmentation function has also been measured and the total rate determined to be 0.74 +/- 0.02 +/- 0.02 K*(892)^0 mesons per hadronic Z^0 decay.Helicity density matrix elements for inclusive K ∗ (892) 0 mesons from hadronic Z 0 decays have been measured over the full range of K ∗ 0 momentum using data taken with the OPAL experiment at LEP. A preference for occupation of the helicity zero state is observed at all scaled momentum x p values above 0.3, with the matrix element ϱ 00 rising to 0.66 ± 0.11 for x p > 0.7. The values of the real part of the off-diagonal element ϱ 1 - 1 are negative at large x p , with a weighted average value of −0.09 ± 0.03 for x p > 0.3, in agreement with new theoretical predictions based on Standard Model parameters and coherent fragmentation of the q q system from the Z 0 decay. All other helicity density matrix elements measured are consistent with zero over the entire x p range. The K ∗ 0 fragmentation function has also been measured and the total rate determined to be 0.74 ± 0.02 ± 0.02 K ∗ (892) 0 mesons per hadronic Z 0 decay

Search for strong gravity in multijet final states produced in pp collisions at √s=13 TeV using the ATLAS detector at the LHC

A search is conducted for new physics in multijet final states using 3.6 inverse femtobarns of data from proton-proton collisions at √s = 13TeV taken at the CERN Large Hadron Collider with the ATLAS detector. Events are selected containing at least three jets with scalar sum of jet transverse momenta (HT) greater than 1TeV. No excess is seen at large HT and limits are presented on new physics: models which produce final states containing at least three jets and having cross sections larger than 1.6 fb with HT > 5.8 TeV are excluded. Limits are also given in terms of new physics models of strong gravity that hypothesize additional space-time dimensions

Operation and performance of the ATLAS semiconductor tracker

The semiconductor tracker is a silicon microstrip detector forming part of the inner tracking system of the ATLAS experiment at the LHC. The operation and performance of the semiconductor tracker during the first years of LHC running are described. More than 99% of the detector modules were operational during this period, with an average intrinsic hit efficiency of (99.74±0.04)%. The evolution of the noise occupancy is discussed, and measurements of the Lorentz angle, δ-ray production and energy loss presented. The alignment of the detector is found to be stable at the few-micron level over long periods of time. Radiation damage measurements, which include the evolution of detector leakage currents, are found to be consistent with predictions and are used in the verification of radiation background simulations

Measurement of the correlation between flow harmonics of different order in lead-lead collisions at √sNN = 2.76 TeV with the ATLAS detector

Correlations between the elliptic or triangular flow coefficients vm (m=2 or 3) and other flow harmonics vn (n=2 to 5) are measured using √sNN=2.76 TeV Pb+Pb collision data collected in 2010 by the ATLAS experiment at the LHC, corresponding to an integrated luminosity of 7 μb−1. The vm−vn correlations are measured in midrapidity as a function of centrality, and, for events within the same centrality interval, as a function of event ellipticity or triangularity defined in a forward rapidity region. For events within the same centrality interval, v3 is found to be anticorrelated with v2 and this anticorrelation is consistent with similar anticorrelations between the corresponding eccentricities, ε2 and ε3. However, it is observed that v4 increases strongly with v2, and v5 increases strongly with both v2 and v3. The trend and strength of the vm−vn correlations for n=4 and 5 are found to disagree with εm−εn correlations predicted by initial-geometry models. Instead, these correlations are found to be consistent with the combined effects of a linear contribution to vn and a nonlinear term that is a function of v22 or of v2v3, as predicted by hydrodynamic models. A simple two-component fit is used to separate these two contributions. The extracted linear and nonlinear contributions to v4 and v5 are found to be consistent with previously measured event-plane correlations

Search for H→γγ produced in association with top quarks and constraints on the Yukawa coupling between the top quark and the Higgs boson using data taken at 7 TeV and 8 TeV with the ATLAS detector

A search is performed for Higgs bosons produced in association with top quarks using the diphoton decay mode of the Higgs boson. Selection requirements are optimized separately for leptonic and fully hadronic final states from the top quark decays. The dataset used corresponds to an integrated luminosity of 4.5 fb−14.5 fb−1 of proton–proton collisions at a center-of-mass energy of 7 TeV and 20.3 fb−1 at 8 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. No significant excess over the background prediction is observed and upper limits are set on the tt¯H production cross section. The observed exclusion upper limit at 95% confidence level is 6.7 times the predicted Standard Model cross section value. In addition, limits are set on the strength of the Yukawa coupling between the top quark and the Higgs boson, taking into account the dependence of the tt¯H and tH cross sections as well as the H→γγ branching fraction on the Yukawa coupling. Lower and upper limits at 95% confidence level are set at −1.3 and +8.0 times the Yukawa coupling strength in the Standard Model