Computational design of dynamic receptor-peptide signaling complexes applied to chemotaxis.

Engineering protein biosensors that sensitively respond to specific biomolecules by triggering precise cellular responses is a major goal of diagnostics and synthetic cell biology. Previous biosensor designs have largely relied on binding structurally well-defined molecules. In contrast, approaches that couple the sensing of flexible compounds to intended cellular responses would greatly expand potential biosensor applications. Here, to address these challenges, we develop a computational strategy for designing signaling complexes between conformationally dynamic proteins and peptides. To demonstrate the power of the approach, we create ultrasensitive chemotactic receptor-peptide pairs capable of eliciting potent signaling responses and strong chemotaxis in primary human T cells. Unlike traditional approaches that engineer static binding complexes, our dynamic structure design strategy optimizes contacts with multiple binding and allosteric sites accessible through dynamic conformational ensembles to achieve strongly enhanced signaling efficacy and potency. Our study suggests that a conformationally adaptable binding interface coupled to a robust allosteric transmission region is a key evolutionary determinant of peptidergic GPCR signaling systems. The approach lays a foundation for designing peptide-sensing receptors and signaling peptide ligands for basic and therapeutic applications

Sub-arc mantle enrichment in the Sunda rear-arc inferred from HFSE systematics in high-K lavas from Java

Many terrestrial silicate reservoirs display a characteristic depletion in Nb, which has been explained in some studies by the presence of reservoirs on Earth with superchondritic Nb/Ta. As one classical example, K-rich lavas from the Sunda rear-arc, Indonesia, have been invoked to tap such a high-Nb/Ta reservoir. To elucidate the petrogenetic processes active beneath the Java rear-arc and the causes for the superchondritic Nb/Ta in some of these lavas, we studied samples from the somewhat enigmatic Javanese rear-arc volcano Muria, which allow conclusions regarding the across-arc variations in volcanic output, source mineralogy and subduction components. We additionally report some data for an along-arc sequence of lavas from the Indonesian part of the Sunda arc, extending from Krakatoa in the west to the islands of Bali and Lombok in the east. We present major and trace element concentrations, Sr–Nd–Hf–Pb isotope compositions, and high-field-strength element (HFSE: Nb, Ta, Zr, Hf, W) concentrations obtained via isotope dilution and MC-ICP-MS analyses. The geochemical data are complemented by melting models covering different source compositions with slab melts formed at variable P–T conditions. The radiogenic isotope compositions of the frontal arc lavas in combination with their trace element systematics confirm previously established regional variations of subduction components along the arc. Melting models show a clear contribution of a sediment-derived component to the HFSE budget of the frontal arc lavas, particularly affecting Zr–Hf and W. In contrast, the K-rich rear-arc lavas tap more hybrid and enriched mantle sources. The HFSE budget of the rear-arc lavas is in particular characterized by superchondritic Nb/Ta (up to 25) that are attributed to deep melting involving overprint by slab melts formed from an enriched garnet–rutile-bearing eclogitic residue. Sub-arc slab melting was potentially triggered along a slab tear beneath the Sunda arc, which is the result of the forced subduction of an oceanic basement relief ~ 8 Myr ago as confirmed by geophysical studies. The purported age of the slab tear coincides with a paucity in arc volcanism, widespread thrusting of the Javanese basement crust as well as the short-lived nature of the K-rich rear-arc volcanism at that time. © 2021, The Author(s)

Structure of self-organized Fe clusters grown on Au(111) analyzed by Grazing Incidence X-Ray Diffraction

We report a detailed investigation of the first stages of the growth of self-organized Fe clusters on the reconstructed Au(111) surface by grazing incidence X-ray diffraction. Below one monolayer coverage, the Fe clusters are in "local epitaxy" whereas the subsequent layers adopt first a strained fcc lattice and then a partly relaxed bcc(110) phase in a Kurdjumov-Sachs epitaxial relationship. The structural evolution is discussed in relation with the magnetic properties of the Fe clusters.Comment: 7 pages, 6 figures, submitted to Physical Review B September 200

On Entangled Multi-particle Systems in Bohmian Theory

Arguments are presented to show that in the case of entangled systems there are certain difficulties in implementing the usual Bohmian interpretation of the wave function in a straightforward manner. Specific examples are given.Comment: 7 page

Search for solar axion emission from 7Li and D(p,gamma)3He nuclear decays with the CAST gamma-ray calorimeter

We present the results of a search for a high-energy axion emission signal from 7Li (0.478 MeV) and D(p,gamma)3He (5.5 MeV) nuclear transitions using a low-background gamma-ray calorimeter during Phase I of the CAST experiment. These so-called "hadronic axions" could provide a solution to the long-standing strong-CP problem and can be emitted from the solar core from nuclear M1 transitions. This is the first such search for high-energy pseudoscalar bosons with couplings to nucleons conducted using a helioscope approach. No excess signal above background was found.Comment: 20 pages, 8 figures, final version to be published in JCA

Influence of Impact Parameter on Thermal Description of Relativistic Heavy Ion Collisions at GSI/SIS

Attention is drawn to the role played by the size of the system in the thermodynamic analysis of particle yields in relativistic heavy ion collisions at SIS energies. This manifests itself in the non-linear dependence of K+ and K- yields in $AA$ collisions at 1 -- 2 A.GeV on the number of participants. It is shown that this dependence can be quantitatively well described in terms of a thermal model with a canonical strangeness conservation. The measured particle multiplicity ratios (pi+/p, pi-/pi+, d/p, K+/pi+ and K+/K- but not eta/pi0) in central Au-Au and Ni-Ni collisions at 0.8 -- 2.0 A.GeV are also explained in the context of a thermal model with a common freeze-out temperature and chemical potential. Including the concept of collective flow a consistent picture of particle energy distributions is derived with the flow velocity being strongly impact-parameter dependent.Comment: revtex, 20 figure

Onset of magnetism in B2 transition metals aluminides

Ab initio calculation results for the electronic structure of disordered bcc Fe(x)Al(1-x) (0.4<x<0.75), Co(x)Al(1-x) and Ni(x)Al(1-x) (x=0.4; 0.5; 0.6) alloys near the 1:1 stoichiometry, as well as of the ordered B2 (FeAl, CoAl, NiAl) phases with point defects are presented. The calculations were performed using the coherent potential approximation within the Korringa-Kohn-Rostoker method (KKR-CPA) for the disordered case and the tight-binding linear muffin-tin orbital (TB-LMTO) method for the intermetallic compounds. We studied in particular the onset of magnetism in Fe-Al and Co-Al systems as a function of the defect structure. We found the appearance of large local magnetic moments associated with the transition metal (TM) antisite defect in FeAl and CoAl compounds, in agreement with the experimental findings. Moreover, we found that any vacancies on both sublattices enhance the magnetic moments via reducing the charge transfer to a TM atom. Disordered Fe-Al alloys are ferromagnetically ordered for the whole range of composition studied, whereas Co-Al becomes magnetic only for Co concentration >0.5.Comment: 11 pages with 9 embedded postscript figures, to be published in Phys.Rev.

Quasars and their host galaxies

This review attempts to describe developments in the fields of quasar and quasar host galaxies in the past five. In this time period, the Sloan and 2dF quasar surveys have added several tens of thousands of quasars, with Sloan quasars being found to z>6. Obscured, or partially obscured quasars have begun to be found in significant numbers. Black hole mass estimates for quasars, and our confidence in them, have improved significantly, allowing a start on relating quasar properties such as radio jet power to fundamental parameters of the quasar such as black hole mass and accretion rate. Quasar host galaxy studies have allowed us to find and characterize the host galaxies of quasars to z>2. Despite these developments, many questions remain unresolved, in particular the origin of the close relationship between black hole mass and galaxy bulge mass/velocity dispersion seen in local galaxies.Comment: Review article, to appear in Astrophysics Update

Orbital state and magnetic properties of LiV_2 O_4

LiV_2 O_4 is one of the most puzzling compounds among transition metal oxides because of its heavy fermion like behavior at low temperatures. In this paper we present results for the orbital state and magnetic properties of LiV_2 O_4 obtained from a combination of density functional theory within the local density approximation and dynamical mean-field theory (DMFT). The DMFT equations are solved by quantum Monte Carlo simulations. The trigonal crystal field splits the V 3d orbitals such that the a_{1g} and e_{g}^{pi} orbitals cross the Fermi level, with the former being slightly lower in energy and narrower in bandwidth. In this situation, the d-d Coulomb interaction leads to an almost localization of one electron per V ion in the a_{1g} orbital, while the e_{g}^{pi} orbitals form relatively broad bands with 1/8 filling. 2The theoretical high-temperature paramagnetic susceptibility chi(T) follows a Curie-Weiss law with an effective paramagnetic moment p_{eff}=1.65 in agreement with the experimental results.Comment: 11 pages, 10 figures, 2 table

Formation and Evolution of Supermassive Black Holes

The correlation between the mass of supermassive black holes in galaxy nuclei and the mass of the galaxy spheroids or bulges (or more precisely their central velocity dispersion), suggests a common formation scenario for galaxies and their central black holes. The growth of bulges and black holes can commonly proceed through external gas accretion or hierarchical mergers, and are both related to starbursts. Internal dynamical processes control and regulate the rate of mass accretion. Self-regulation and feedback are the key of the correlation. It is possible that the growth of one component, either BH or bulge, takes over, breaking the correlation, as in Narrow Line Seyfert 1 objects. The formation of supermassive black holes can begin early in the universe, from the collapse of Population III, and then through gas accretion. The active black holes can then play a significant role in the re-ionization of the universe. The nuclear activity is now frequently invoked as a feedback to star formation in galaxies, and even more spectacularly in cooling flows. The growth of SMBH is certainly there self-regulated. SMBHs perturb their local environment, and the mergers of binary SMBHs help to heat and destroy central stellar cusps. The interpretation of the X-ray background yields important constraints on the history of AGN activity and obscuration, and the census of AGN at low and at high redshifts reveals the downsizing effect, already observed for star formation. History appears quite different for bright QSO and low-luminosity AGN: the first grow rapidly at high z, and their number density decreases then sharply, while the density of low-luminosity objects peaks more recently, and then decreases smoothly.Comment: 31 pages, 13 figures, review paper for Astrophysics Update