| 1. |
- Abelev, Betty, et al.
(författare)
-
Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
-
Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
|
|
| 2. |
- Abelev, Betty, et al.
(författare)
-
Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
-
Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
-
Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-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 vertical bar y vertical bar < 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 chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. 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 (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
|
|
| 3. |
- Abelev, Betty, et al.
(författare)
-
Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
-
Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
-
Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
|
|
| 4. |
- Ademuyiwa, Adesoji O., et al.
(författare)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
|
|
| 5. |
- Andre, Ingemar, et al.
(författare)
-
Computational assessment of folding energy landscapes in heterodimeric coiled coils
- 2018
-
Ingår i: Proteins. - : Wiley-Blackwell. - 0887-3585 .- 1097-0134. ; 86:7, s. 790-801
-
Tidskriftsartikel (refereegranskat)abstract
- The coiled coil structural motif consists of alpha helices supercoiling around each other to form staggered knobs-into-holes packing. Such structures are deceptively simple, especially as they often can be described with parametric equations, but are known to exist in various conformations. Even the simplest systems, consisting of 2 monomers, can assemble into a wide range of states. They can form canonical as well as noncanonical coiled coils, be parallel or antiparallel, where helices associate with different degrees of shift, tilt, and rotation. Here, we investigate the energy landscape of heterodimeric coiled coils by carrying out de novo folding simulations starting from amino acid sequence. We folded a diverse set of 22 heterodimers and demonstrate that the approach is capable of identifying the atomic details in the experimental structure in the majority of cases. Our methodology also enables exploration of alternative states that can be accessible in solution beyond the experimentally determined structure. For many systems, we observe folding energy landscapes with multiple energy minima and several isoenergetic states. By comparing coiled coils from single domains and those extracted from larger proteins, we find that standalone coiled coils have deeper energy wells at the experimentally determined conformation. By folding the competing homodimeric states in addition to the heterodimers, we observe that the structural specificity towards the heteromeric state is often small. Taken together, our results demonstrate that de novo folding simulations can be a powerful tool to characterize structural specificity of coiled coils when coupled to assessment of energy landscapes.
|
|
| 6. |
- André, Ingemar, et al.
(författare)
-
Measurement of Ca2+-binding constants of proteins and presentation of the CaLigator software.
- 2002
-
Ingår i: Analytical Biochemistry. - : Elsevier BV. - 1096-0309 .- 0003-2697. ; 305:2, s. 195-205
-
Tidskriftsartikel (refereegranskat)abstract
- The complexity of Ca2+ cell signaling is dependent on a plethoria of Ca2+-binding proteins that respond to signals in different ranges of Ca2+ concentrations. Since the function of these proteins is directly coupled to their Ca2+-binding properties, there is a need for accurately determined equilibrium Ca2+-binding constants. In this work we outline the experimental techniques available to determine Ca2+-binding constants in proteins, derive the models used to describe the binding, and present CaLigator, software for least-square fitting directly to the measured quantity. The use of the software is illustrated for Ca2+-binding data obtained for two deamidated forms of calbindin D(9k), either an isospartate-56 (beta form) or a normal Asp-56 (alpha form). Here, the Ca2+-binding properties of the two isoforms have been studied using the chelator method. The alpha form shows similar Ca2+-binding properties to the wild type while the beta form has lost both cooperativety and affinity.
|
|
| 7. |
- André, Ingemar
(författare)
-
Modeling the structure of helical assemblies with experimental constraints in Rosetta
- 2018
-
Ingår i: Methods in Molecular Biology. - New York, NY : Springer New York. - 1064-3745. ; 1764, s. 475-489
-
Bokkapitel (refereegranskat)abstract
- Determining high-resolution structures of proteins with helical symmetry can be challenging due to limitations in experimental data. In such instances, structure-based protein simulations driven by experimental data can provide a valuable approach for building models of helical assemblies. This chapter describes how the Rosetta macromolecular package can be used to model homomeric protein assemblies with helical symmetry in a range of modeling scenarios including energy refinement, symmetrical docking, comparative modeling, and de novo structure prediction. Data-guided structure modeling of helical assemblies with experimental information from electron density, X-ray fiber diffraction, solid-state NMR, and chemical cross-linking mass spectrometry is also described.
|
|
| 8. |
- André, Ingemar
(författare)
-
Protein Interactions: Electrostatics and Ligand Binding
- 2005
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals with Ca2+ binding to proteins, electrostatic interactions in and between proteins as well as inter- and intramolecular interactions. A computer program was developed to determine Ca2+ binding constants from experimental titration data of proteins. We further studied the effect of deamidation in the Ca2+ binding site of Calbindin D9k on the Ca2+ binding and cooperativity and conclude that introduction of b-peptide linkage leads to a reduction of both binding and cooperativity. The binding of Ca2+ to the individual EF-hands of Calbindin D28k and the coupling of Ca2+ binding to oligomerization was studied by analysis of Ca2+ binding at different protein concentrations and computer fitting of data to a 4- or 6-state model. Three different modes of coupling between Ca2+ binding and oligomerization emerge for the studied EF-hands, which allows for interpretation of their position within the intact protein. The importance of electrostatic interaction for the binding of a highly positively charged peptide to the negatively charged calmodulin was studied. Charge mutations and variations in protein and peptide, together with changes in pH and salt content allow us to experimentally verify the importance of electrostatic interactions. Experimental results were coupled to simulations and it was concluded that the system is surprisingly invariant to changes in the charge state of protein and peptide. This insensitivity is caused by the high charge of the system, which behaves as it is "saturated" with charge, and a charge regulation at lower pH. Furthermore, we find that binding is optimal at physiological conditions and that binding affinity of two oppositely charged binding partners can be increased by screening of electrostatic interactions. We propose a model to explain the data. Electrostatic interactions can be studied by determining pKa values of titrating groups in proteins. A heteronuclear NMR method was developed to study the charge state of arginine and lysine residues in proteins and to determine pKa values. The method was applied to apo-calmodulin where site-specific pKa values of lysine residues were determined. In another project the pKa values of acidic groups in a variant of protein GB1 in low and high ionic strength was determined using NMR. This allowed for the pH dependence of protein stability to be determined. From this data it can be concluded that the unfolded state contains residual structure. Many of the proton titration curves are significantly non-ideal and to analyze this data we propose new methods to visualize and analyze cooperativity of proton binding. The conformation of C4BP-binding region of M proteins derived from streptococcus pyogenes was investigated in isolation and in complex with C4BPa-12 using NMR. We conclude that this region adopts a coiled-coil and that it binds in an extended shape in the complex. The importance of tertiary contacts on secondary structure formation was studied by searching for fragments in the PDB database which can adopt different secondary structure depending on depending on the protein framework. We conclude that secondary structure switching is rare and that there is a strong inherent propensity in structured segments to form only one type of secondary structure.
|
|
| 9. |
- André, Ingemar, et al.
(författare)
-
Residue-specific pK(a) determination of lysine and arginine side chains by indirect N-15 and C-13 NMR spectroscopy: Application to apo calmodulin
- 2007
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 129:51, s. 15805-15813
-
Tidskriftsartikel (refereegranskat)abstract
- Electrostatic interactions in proteins can be probed experimentally through determination of residue-specific acidity constants, We describe here triple-resonance NMR techniques for direct determination of lysine and arginine side-chain protonation states in proteins. The experiments are based on detection of nonexchangeable protons over the full range of pH and temperature and therefore are well suited for pK(a) determination of individual amino acid side chains. The experiments follow the side-chain N-15(zeta) (lysine) and N-15(epsilon) or C-13(zeta) (arginine) chemical shift, which changes due to sizable changes in the heteronuclear electron distribution upon (de)protonation. Since heteronuclear chemical shifts are overwhelmed by the charge state of the amino acid side chain itself, these methods supersede H-1-based NMR in terms of accuracy, sensitivity, and selectivity. Moreover, the N-15(zeta) and N-15(epsilon) nuclei may be used to probe changes in the local electrostatic environment. Applications to three proteins are described: apo calmodulin, calbindin D-9k, and FKBP12. For apo calmodulin, residue-specific pK(a) values of lysine side chains were determined to fall between 10.7 and 11.2 as a result of the high net negative charge on the protein surface. Ideal two-state titration behavior observed for all lysines indicates the absence of significant direct charge interactions between the basic residues. These results are compared with earlier studies based on chemical modification.
|
|
| 10. |
- André, Ingemar, et al.
(författare)
-
Salt enhances calmodulin-target interaction
- 2006
-
Ingår i: Biophysical Journal. - : Elsevier BV. - 1542-0086 .- 0006-3495. ; 90:8, s. 2903-2910
-
Tidskriftsartikel (refereegranskat)abstract
- Calmodulin (CaM) operates as a Ca2+ sensor and is known to interact with and regulate hundreds of proteins involved in a great many aspects of cellular function. It is of considerable interest to understand the balance of forces in complex formation of CaM with its target proteins. Here we have studied the importance of electrostatic interactions in the complex between CaM and a peptide derived from smooth-muscle myosin light-chain kinase by experimental methods and Monte Carlo simulations of electrostatic interactions. We show by Monte Carlo simulations that, in agreement with experimental data, the binding affinity between CaM and highly charged peptides is surprisingly insensitive to changes in the net charge of both the protein and peptide. We observe an increase in the binding affinity between oppositely charged partners with increasing salt concentration from zero to 100 mM, showing that formation of globular CaM-kinase type complexes is facilitated at physiological ionic strength. We conclude that ionic interactions in complex formation are optimized at pH and saline similar to the cell environment, which probably overrules the electrostatic repulsion between the negatively charged Ca2+-binding domains of CaM. We propose a conceivable rationalization of CaM electrostatics associated with interdomain repulsion.
|
|
