Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von hippel-lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities

E3 ubiquitin ligases are attractive targets in the ubiquitin-proteasome system, however, the development of small-molecule ligands has been rewarded with limited success. The von Hippel-Lindau protein (pVHL) is the substrate recognition subunit of the VHL E3 ligase that targets HIF-1α for degradation. We recently reported inhibitors of the pVHL:HIF-1α interaction, however they exhibited moderate potency. Herein, we report the design and optimization, guided by X-ray crystal structures, of a ligand series with nanomolar binding affinities

Phonon Dynamics and Multipolar Isomorphic Transition in beta-pyrochlore KOs2O6

We investigate with a microscopic model anharmonic K-cation oscillation observed by neutron experiments in beta-pyrochlore superconductor KOs2O6, which also shows a mysterious first-order structural transition at Tp=7.5 K. We have identified a set of microscopic model parameters that successfully reproduce the observed temperature dependence and the superconducting transition temperature. Considering changes in the parameters at Tp, we can explain puzzling experimental results about electron-phonon coupling and neutron data. Our analysis demonstrates that the first-order transition is multipolar transition driven by the octupolar component of K-cation oscillations. The octupole moment does not change the symmetry and is characteristic to noncentrosymmetric K-cation potential.Comment: 5 pages, 4 figures, submitted to J. Phys. Soc. Jp

Superconductivity and Rattling under High Pressure in the beta-Pyrochlore Oxide RbOs2O6

Rattling-induced superconductivity in the beta-pyrochlore oxide RbOs2O6 is investigated under high pressures up to 6 GPa. Resistivity measurements in a high-quality single crystal show that the superconducting transition temperature Tc increases gradually from 6.3 K at ambient pressure to 8.8 K at 3.5 GPa, surprisingly remains almost constant at 8.8 \pm 0.1 K in a wide pressure range between 3.5 (Po) and 4.8 GPa, and suddenly drops to 6.3 K at Ps = 4.9 GPa, followed by a gradual decrease with further pressure increase. Two anomalies in the temperature dependence of the normal-state resistivity are observed at Po Ps, revealing the presence of two high-pressure phases corresponding to the changes in Tc. The rattling of the Rb ion inside a cage made of Os and O atoms may be slightly and seriously modified in these high-pressure phases that probably have cages of reduced symmetry, respectively, so that electron-rattler interactions that govern the superconducting and transport properties of beta-RbOs2O6 are significantly affected.Comment: arXiv admin note: text overlap with arXiv:1009.035

Seismic Vulnerability Assessment of Priority Cultural Heritage Structures in the Philippines

At the end of 2013 two catastrophic events occurred in the Philippines: the M 7.2 earthquake in Bohol and the strongest ever recorded Typhoon Haiyan, causing destruction across the islands of Cebu, Bohol and the Visayas region. These events raised the need to carry out a multi-hazard risk assessment of heritage buildings, many of which were irretrievably lost in the disasters. Philippines’ Department of Tourism engaged ARS Progetti S.P.A., Rome, Italy, and the Center for Conservation of Cultural Property and Environment in the Tropics (CCCPET), University of Sto. Tomas, Manila, to undertake the “Assessment of the Multi-Hazard Vulnerability of Priority Cultural Heritage Structures in the Philippines”, with experts from University College London, UK, and De La Salle University. The main objective of the project was to reduce the vulnerability of cultural heritage structures to multiple natural hazards, including earthquake, typhoon, flood, by: (i) prioritizing of specific structures based on hazard maps and historical records; (ii) assessing their vulnerability; and (iii) recommending options to mitigate the impacts on them. The paper presents the methodology introduced to determine the seismic risk these heritage buildings are exposed to. All the selected cultural heritage structures are under the jurisdiction of the National Museum Commission of Philippines and of the National Commission for Culture and Arts

Evolution of quantum criticality in the system CeNi9Ge4

The heavy fermion system CeNi9Ge4 exhibits a paramagnetic ground state with remarkable features such as: a record value of the electronic specific heat coefficient in systems with a paramagnetic ground state, \gamma = C/T \simeq 5.5 J/molK^2 at 80 mK, a temperature-dependent Sommerfeld-Wilson ratio, R=\chi/\gamma, below 1 K and an approximate single ion scaling of the 4f-magnetic specific heat and susceptibility. These features are related to a rather small Kondo energy scale of a few Kelvin in combination with a quasi-quartet crystal field ground state. Tuning the system towards long range magnetic order is accomplished by replacing a few at.% of Ni by Cu or Co. Specific heat, susceptibility and resistivity studies reveal T_N \sim 0.2 K for CeNi8CuGe4 and T_N \sim 1 K for CeNi8CoGe4. To gain insight whether the transition from the paramagnetic NFL state to the magnetically ordered ground state is connected with a heavy fermion quantum critical point we performed specific heat and ac susceptibility studies and utilized the \mu SR technique and quasi-elastic neutron scattering.Comment: 8 pages, 3 figures, will be published in J.Phys.: Conf. Series (Proceedings of the International & Interdisciplinary Workshop on Novel Phenomena in Intergrated Comples Sciences: From Living to Non-living Systems, Japan, held in Kyoto, October 11-14, 2010

Infrared and optical properties of pure and cobalt-doped LuNi_2B_2C

We present optical conductivity data for Lu(Ni$_{1-x}$Co$_x$)$_2$B$_2$C over a wide range of frequencies and temperatures for x=0 and x=0.09. Both materials show evidence of being good Drude metals with the infrared data in reasonable agreement with dc resistivity measurements at low frequencies. An absorption threshold is seen at approximately 700 cm-1. In the cobalt-doped material we see a superconducting gap in the conductivity spectrum with an absorption onset at 24 +/- 2 cm-1 = 3.9$ +/- 0.4 k_BT_c suggestive of weak to moderately strong coupling. The pure material is in the clean limit and no gap can be seen. We discuss the data in terms of the electron-phonon interaction and find that it can be fit below 600 cm-1 with a plasma frequency of 3.3 eV and an electron-phonon coupling constant lambda_{tr}=0.33 using an alpha^{2}F(omega) spectrum fit to the resistivity.Comment: 10 pages with 10 embedded figures, submitted to PR

Crystalline Color Superconductivity

In any context in which color superconductivity arises in nature, it is likely to involve pairing between species of quarks with differing chemical potentials. For suitable values of the differences between chemical potentials, Cooper pairs with nonzero total momentum are favored, as was first realized by Larkin, Ovchinnikov, Fulde and Ferrell (LOFF). Condensates of this sort spontaneously break translational and rotational invariance, leading to gaps which vary periodically in a crystalline pattern. Unlike the original LOFF state, these crystalline quark matter condensates include both spin zero and spin one Cooper pairs. We explore the range of parameters for which crystalline color superconductivity arises in the QCD phase diagram. If in some shell within the quark matter core of a neutron star (or within a strange quark star) the quark number densities are such that crystalline color superconductivity arises, rotational vortices may be pinned in this shell, making it a locus for glitch phenomena.Comment: 40 pages, LaTeX with eps figs. v2: New paragraph on Ginzburg-Landau treatment of LOFF phase in section 5. References added. v3: Small changes only. Version to appear in Phys. Rev.

Inhomogeneous Superconductivity in Condensed Matter and QCD

Inhomogeneous superconductivity arises when the species participating in the pairing phenomenon have different Fermi surfaces with a large enough separation. In these conditions it could be more favorable for each of the pairing fermions to stay close to its Fermi surface and, differently from the usual BCS state, for the Cooper pair to have a non zero total momentum. For this reason in this state the gap varies in space, the ground state is inhomogeneous and a crystalline structure might be formed. This situation was considered for the first time by Fulde, Ferrell, Larkin and Ovchinnikov, and the corresponding state is called LOFF. The spontaneous breaking of the space symmetries in the vacuum state is a characteristic feature of this phase and is associated to the presence of long wave-length excitations of zero mass. The situation described here is of interest both in solid state and in elementary particle physics, in particular in Quantum Chromo-Dynamics at high density and small temperature. In this review we present the theoretical approach to the LOFF state and its phenomenological applications using the language of the effective field theories.Comment: RevTex, 83 pages, 26 figures. Submitted to Review of Modern Physic

Pairing competition in a quasi-one-dimensional model of organic superconductors (TMTSF)2X_{2}X in magnetic field

We microscopically study the effect of the magnetic field (Zeeman splitting) on the superconducting state in a model for quasi-one-dimensional organic superconductors (TMTSF)$_{2}X$. We investigate the competition between spin singlet and spin triplet pairings and the Fulde-Ferrell-Larkin-Ovchinnikov(FFLO) state by random phase approximation. While we studied the competition by comparison with the eigenvalue of the gap equation at a fixed temperature in our previous study (Phys. Rev. Lett. \textbf{102} (2009) 016403), here we obtain both the $T_c$ for each pairing state and a phase diagram in the $T$(temperature)-$h_z$(field)-$V_y$(strength of the charge fluctuation) space. The phase diagram shows that consecutive transitions from singlet pairing to the FFLO state and further to $S_z=1$ triplet pairing can occur upon increasing the magnetic field when $2k_{F}$ charge fluctuations coexist with $2k_{F}$ spin fluctuations. In the FFLO state, the singlet d-wave and $S_{z}=0$ triplet $f$-wave components are strongly mixed especially when the charge fluctuations are strong.Comment: 11 pages, 9 figure

Fulde-Ferrell-Larkin-Ovchinnikov State in Heavy Fermion Superconductors

The Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state is a novel superconducting state in a strong magnetic field characterized by the formation of Cooper pairs with nonzero total momentum (k \uparrow, -k+q \downarrow), instead of the ordinary BCS pairs (k \uparrow, -k \downarrow). A fascinating aspect of the FFLO state is that it exhibits inhomogeneous superconducting phases with a spatially oscillating order parameter and spin polarization. The FFLO state has been of interest in various research fields, not only in superconductors in solid state physics, but also in neutral Fermion superfluid of ultracold atomic gases and in color superconductivity in high energy physics. In spite of extensive studies of various superconductors, there has been no undisputed experimental verification of the FFLO state, mainly because of the very stringent conditions required of the superconducting materials. Among several classes of materials, certain heavy fermion and organic superconductors are believed to provide conditions that are favorable to the formation of the FFLO state. This review presents recent experimental and theoretical developments of the FFLO state mainly in heavy fermion superconductors. In particular we address the recently discovered quasi-two-dimensional superconductor CeCoIn_5, which is a strong candidate for the formation of the FFLO state.Comment: 17 pages, 12 figures with jpsf2.cls, to be published in J. Phys. Soc. Jpn. (Special Topics - Frontiers of Novel Superconductivity in Heavy Fermion Compounds