The Chronus Quantum software package

The Chronus Quantum (ChronusQ) software package is an open source (under the GNU General Public License v2) software infrastructure which targets the solution of challenging problems that arise in ab initio electronic structure theory. Special emphasis is placed on the consistent treatment of time dependence and spin in the electronic wave function, as well as the inclusion of relativistic effects in said treatments. In addition, ChronusQ provides support for the inclusion of uniform finite magnetic fields as external perturbations through the use of gauge-including atomic orbitals. ChronusQ is a parallel electronic structure code written in modern C++ which utilizes both message passing implementation and shared memory (OpenMP) parallelism. In addition to the examination of the current state of code base itself, a discussion regarding ongoing developments and developer contributions will also be provided. This article is categorized under: Software > Quantum Chemistry Electronic Structure Theory > Ab Initio Electronic Structure Methods Electronic Structure Theory > Density Functional Theory

T-Cell Memory Responses Elicited by Yellow Fever Vaccine are Targeted to Overlapping Epitopes Containing Multiple HLA-I and -II Binding Motifs

The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env) and nonstructural (NS) proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4+ and CD8+ T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, "promiscuous" T-cell antigens might contribute to the high efficacy of the yellow fever vaccines. © 2013 de Melo et al

DODAB and DODAC bilayer-like aggregates in the micromolar surfactant concentration domain

In the millimolar concentration domain (typically 1 mM), dioctadecyldimethylammonium bromide and chloride (DODAX, X representing Br- or Cl- counterions) molecules assemble in water as large unilamellar vesicles. Differential scanning calorimetry (DSC) is a suitable technique to obtain the melting temperature (Tm) characteristic of surfactant bilayers, while fluorescence spectroscopy detects formation of surfactant aggregates, like bilayers. These two techniques were combined to investigate the assemble of DODAX molecules at micromolar concentrations, from 10 to 100 micromolar. At 1 mM surfactant, Tm ~ 45 ºC and 49 oC, respectively for DODAB and DODAC. DSC and fluorescence of Nile Red were used to show the formation of DODAX aggregates, at the surfactant concentration as low as 10 micromolar, whose Tm decreases monotonically with increasing DODAX concentration to attain the value for the ordinary vesicles. The data indicate that these aggregates are organized as bilayer-like structures.Fundação para a Ciência e a Tecnologia (FCT

Cellular Automata Applications in Shortest Path Problem

Cellular Automata (CAs) are computational models that can capture the essential features of systems in which global behavior emerges from the collective effect of simple components, which interact locally. During the last decades, CAs have been extensively used for mimicking several natural processes and systems to find fine solutions in many complex hard to solve computer science and engineering problems. Among them, the shortest path problem is one of the most pronounced and highly studied problems that scientists have been trying to tackle by using a plethora of methodologies and even unconventional approaches. The proposed solutions are mainly justified by their ability to provide a correct solution in a better time complexity than the renowned Dijkstra's algorithm. Although there is a wide variety regarding the algorithmic complexity of the algorithms suggested, spanning from simplistic graph traversal algorithms to complex nature inspired and bio-mimicking algorithms, in this chapter we focus on the successful application of CAs to shortest path problem as found in various diverse disciplines like computer science, swarm robotics, computer networks, decision science and biomimicking of biological organisms' behaviour. In particular, an introduction on the first CA-based algorithm tackling the shortest path problem is provided in detail. After the short presentation of shortest path algorithms arriving from the relaxization of the CAs principles, the application of the CA-based shortest path definition on the coordinated motion of swarm robotics is also introduced. Moreover, the CA based application of shortest path finding in computer networks is presented in brief. Finally, a CA that models exactly the behavior of a biological organism, namely the Physarum's behavior, finding the minimum-length path between two points in a labyrinth is given.Comment: To appear in the book: Adamatzky, A (Ed.) Shortest path solvers. From software to wetware. Springer, 201

New structural insights into the role of TROVE2 complexes in the on-set and pathogenesis of systemic lupus eythematosus determined by a combiantion of QCM-D and DPI

The final publication is available at link.springer.com.[EN] The mechanism of self-recognition of the autoantigen TROVE2, a common biomarker in autoimmune diseases, has been studied with a quartz crystal microbalance with dissipation monitoring (QCM-D) and dual polarization interferometry (DPI). The complementarity and remarkable analytical features of both techniques has allowed new insights into the onset of systemic lupus erythematosus (SLE) to be achieved at the molecular level. The in vitro study for SLE patients and healthy subjects suggests that anti-TROVE2 autoantibodies may undergo an antibody bipolar bridging. An epitope-paratope-specific binding initially occurs to activate a hidden Fc receptor in the TROVE2 tertiary structure. This bipolar mechanism may contribute to the pathogenic accumulation of anti-TROVE2 autoantibody immune complex in autoimmune disease. Furthermore, the specific calcium-dependent protein-protein bridges point out at how the TRIM21/TROVE2 association might occur, suggesting that the TROVE2 protein could stimulate the intracellular immune signaling via the TRIM21 PRY-SPRY domain. These findings may help to better understand the origins of the specificity and affinity of TROVE2 interactions, which might play a key role in the SLE pathogenesis. This manuscript gives one of the first practical applications of two novel functions (-df/dD and Delta h/molec) for the analysis of the data provided by QCM-D and DPI. In addition, it is the first time that QCM-D has been used for mapping hidden Fc receptors as well as linear epitopes in a protein tertiary structure.We would like to thank Sylvia Daunert for her invaluable help with the discussion of the paper. Furthermore, we acknowledge financial support from the Generalitat Valenciana (GVA-PROMETEOII/2014/040) as well as the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund under award numbers CTQ2013-45875-R and CTQ2013-42914-RJuste-Dolz, AM.; Do Nascimento, NM.; Monzó, IS.; Grau-García, E.; Roman-Ivorra, JA.; López-Paz, JL.; Escorihuela Fuentes, J.... (2019). New structural insights into the role of TROVE2 complexes in the on-set and pathogenesis of systemic lupus eythematosus determined by a combiantion of QCM-D and DPI. Analytical and Bioanalytical Chemistry. 411(19):4709-4720. https://doi.org/10.1007/s00216-018-1407-xS4709472041119Kakatia S, Teronpia R, Barmanb B. Frequency, pattern and determinants of flare in systemic lupus erythematosus: a study from North East India. Egypt Rheumatol. 2015;37:S55–9.Kuhn A, Wenzel J, Weyd H. Photosensitivity, apoptosis, and cytokines in the pathogenesis of lupus erythematosus: a critical review. Clinic Rev Allerg Immunol. 2014;47:148–62.American Lupus Foundation. 2016. http://www.lupus.org .World Health Organization. Environmental health criteria 236. Geneva: WHO Press; 2006.Li W, Titov AA, Morel L. An update on lupus animal models. Curr Opin Rheumatol. 2017;29:1040–8711.Routsias JG, Tzioufas AG, Moutsopoulos HM. The clinical value of intracellular autoantigens B-cell epitopes in systemic rheumatic diseases. Clin Chim Acta. 2004;340:1–25.Franceschini F, Cavazzana I. Anti-Ro/SSA and La/SSB antibodies. Autoimmunity. 2005;38:55–63.Kelekar A, Saitta MR, Keene JD. Molecular composition of Ro small ribonucleoprotein complexes in human cells. Intracellular localization of the 60- and 52-kD proteins. J Clin Ivest. 1994;93:1637–44.Slobbe RL, Pluk W, van Venrooij WJ, Prujin GJM. Ro ribonucleoprotein assembly in vitro: identification of RNA-protein and protein-protein interactions. J Mol Biol. 1992;2:361–6.Chen X, Taylor DW, Fowler CC, Galan JE, Wang HW, Wolin SL. An RNA degradation machine sculpted by Ro autoantigen and noncoding RNA. Cell. 2013;153:166–77.Stein AJ, Fuchs G, Fu C, Wolin SL, Reinisch KM. Structural insights into RNA quality control: the Ro autoantigen binds misfolded RNAs via its central cavity. Cell. 2005;121:529–39.Reed JH, Gordon TP. Autoimmunity: Ro60-associated RNA takes its toll on disease pathogenesis. Nat Rev Rheumatol. 2016;12:136–8.Sim S, Weinberg DE, Fuchs G, Choi K, Chung J, Wolin SL. The subcellular distribution of an RNA quality control protein, the Ro autoantigen, is regulated by noncoding Y RNA binding. Mol Biol Cell. 2009;20:1555–64.Reed JH, Jackson MW, Gordon TP. A B cell apotope of Ro 60 in systemic lupus erythematosus. Arthritis Rheum. 2008;58:1125–9.Wolin SL, Reinisch KM. The Ro 60 kDa autoantigen comes into focus: interpreting epitope mapping experiments on the basis of structure. Autoimmun Rev. 2006;5:367–72.Routsias JG, Tzioufas AG. B-cell epitopes of the intracellular autoantigens Ro/SSA and La/SSB: tools to study the regulation of the autoimmune response. J Autoimmun. 2010;35:256–64.Whittaker CA, Hynes RO. Distribution and evolution of von Willebrand/integrin a domains: widely dispersed domains with roles in cell adhesion and elsewere. Mol Bio Cell. 2002;13:3369–87.Lacy DB, Wigelsworth DJ, Scobie HM, Young JA, Collier RJ. Crystal structure of the von Willebrand factor a domain of human capillary morphogenesis protein 2: an anthrax toxin receptor. Proc Natl Acad Sci U S A. 2004;101:6367–72.O’Brien CA, Wolin SL. A possible role for the 60-kD Ro autoantigen in a discard pathway for defective 5S rRNA precursors. Genes Dev. 1994;8:2891–903.Chen X, Wolin SL. The Ro 60 autoantigen : insights into cellular function and role in autoimmunity. J Mol Med (Berl). 2004;82:232–9.Escorihuela J, González-Martínez MA, López-Paz JL, Puchades R, Maquieira A, Gimenez-Romero D. Dual-polarization interferometry: a novel technique to light up the nanomolecular world. Chem Rev. 2014;115:265–94.do Nascimento NM, Juste-Dolz A, Bueno PR, Monzó I, Tejero R, Lopez-Paz JL, et al. Mapping molecular binding by means of conformational dynamics measurements. RSC Adv. 2018;8:867–76.do Nascimento NM, Juste-Dolz A, Grau-García E, Román-Ivorra J, Puchades R, Maquieira A, et al. Label-free piezoelectric biosensor for prognosis and diagnosis of systemic lupus erythematosus. Biosens. Bioelectron. 2016;90:166–73.Seo MH, Park J, Kim E, Hohng S, Kim HS. Protein conformational dynamics dictate the binding affinity for a ligand. Nat Commun. 2014;5:3724.Lakshmanan RS, Efremov V, O’Donnell JS, Killard AJ. Measurement of the viscoelastic properties of blood plasma clot formation in response to tissue factor concentration-dependent activation. Anal Bioanal Chem. 2016;408:6581–8.Fakhrullin RF, Vinter VG, Zamaleeva AI, Matveeva MV, Kourbanov RA, Temesgen BK, et al. Quartz crystal microbalance immunosensor for the detection of antibodies to double-stranded DNA. Anal Bioanl Chem. 2007;388:367–75.Shen F, Rojas OJ, Genzer J, Gurgel PV, Carbonell RG. Affinity interactions of human immunoglobulin G with short peptides: role of ligand spacer on binding, kinetics, and mass transfer. Anal Bioanl Chem. 2015;408:1829–41.Fogarty AC, Laage D. Water dynamics in protein hydration shells: the molecular origins of the dynamical perturbation. J Phys Chem B. 2014;118:7715–29.Born B, Kim SJ, Ebbinghaus S, Gruebelebc M, Havenith M. The terahertz dance of water with the proteins: the effect of protein flexibility on the dynamical hydration shell of ubiquitin. Faraday Discuss. 2009;141:161–73.Yoshimi R, Ueda A, Ozato K, Ishigatsubo Y. Clinical and pathological roles of Ro/SSA autoantibody system. Clin Dev Immunol. 2012;2012:606195.Boire G, Gendron M, Monast N, Bastin B, Ménard HA. Purification of antigenically intact Ro ribonucleoproteins; biochemical and immunological evidence that the 52-kD protein is not a Ro protein. Clin Exp Immunol. 1995;100:489–98.Gazzaruso C, Montecucco CM, Geroldi D, Garzaniti A, Finardi G. Severe hypercalcemia and systemic lupus erythematosus. Joint Bone Spine. 2000;67:485–8.Hassan AB, Lundberg IE, Isenberg D, Wahren-Herlenius M. Serial analysis of Ro/SSA and La/SSB antibody levels and correlation with clinical disease activity in patients with systemic lupus erythematosus. Scand J Rheumatol. 2002;31:133–9.Huang RY, Chen G. Higher order structure characterization of protein therapeutics by hydrogen/deuterium exchange mass spectrometry. Anal Bioanal Chem. 2014;406:6541–58.Yu F, Roy S, Arevalo E, Schaeck J, Wang J, Holte K, et al. Characterization of heparin-protein interaction by saturation transfer difference (STD) NMR. Anal Bioanal Chem. 2014;406:3079–89.Rizzuto R, Pozzan T. Microdomains of intracellular Ca2+: molecular determinants and functional consequences. Physiol Rev. 2006;86:369–408.Gaipl US, Kuhn A, Sheriff A, Munoz LE, Franz S, Voll RE, et al. Clearance of apoptotic cells in human SLE. Curr Dir Autoimmun. 2006;9:173–87.Falati S, Edmead CE, Poole AW. Glycoprotein Ib-V-IX, a receptor for Von Willebrand factor, couples physically and functionally to the Fc receptor gamma-chain, Fyn, and Lyn to activate human platelets. Blood. 1999;94:1648–56.Muñoz LE, Lauber K, Schiller M, Manfredi AA, Herrmann M. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol. 2010;6:280–9