Microwave Spectroscopy of Thermally Excited Quasiparticles in YBa_2Cu_3O_{6.99}

We present here the microwave surface impedance of a high purity crystal of $YBa_2Cu_3O_{6.99}$ measured at 5 frequencies between 1 and 75 GHz. This data set reveals the main features of the conductivity spectrum of the thermally excited quasiparticles in the superconducting state. Below 20 K there is a regime of extremely long quasiparticle lifetimes, due to both the collapse of inelastic scattering below $T_c$ and the very weak impurity scattering in the high purity $BaZrO_3$-grown crystal used in this study. Above 20 K, the scattering increases dramatically, initially at least as fast as $T^4$.Comment: 13 pages with 10 figures. submitted to Phys Rev

Microwave Electrodynamics of Electron-Doped Cuprate Superconductors

We report microwave cavity perturbation measurements of the temperature dependence of the penetration depth, lambda(T), and conductivity, sigma(T) of Pr_{2-x}Ce_{x}CuO_{4-delta} (PCCO) crystals, as well as parallel-plate resonator measurements of lambda(T) in PCCO thin films. Penetration depth measurements are also presented for a Nd_{2-x}Ce_{x}CuO_{4-delta} (NCCO) crystal. We find that delta-lambda(T) has a power-law behavior for T<T_c/3, and conclude that the electron-doped cuprate superconductors have nodes in the superconducting gap. Furthermore, using the surface impedance, we have derived the real part of the conductivity, sigma_1(T), below T_c and found a behavior similar to that observed in hole-doped cuprates.Comment: 4 pages, 4 figures, 1 table. Submitted to Physical Review Letters revised version: new figures, sample characteristics added to table, general clarification give

Structural Basis for the Inhibitory Effects of Ubistatins in the Ubiquitin-Proteasome Pathway

The discovery of ubistatins, small molecules that impair proteasomal degradation of proteins by directly binding to polyubiquitin, makes ubiquitin itself a potential therapeutic target. Although ubistatins have the potential for drug development and clinical applications, the lack of structural details of ubiquitin-ubistatin interactions has impeded their development. Here, we characterized a panel of new ubistatin derivatives using functional and binding assays. The structures of ubiquitin complexes with ubistatin B and hemi-ubistatin revealed direct interactions with ubiquitin's hydrophobic surface patch and the basic/polar residues surrounding it. Ubistatin B binds ubiquitin and diubiquitin tighter than a high-affinity ubiquitin receptor and shows strong preference for K48 linkages over K11 and K63. Furthermore, ubistatin B shields ubiquitin conjugates from disassembly by a range of deubiquitinases and by the 26S proteasome. Finally, ubistatin B penetrates cancer cells and alters the cellular ubiquitin landscape. These findings highlight versatile properties of ubistatins and have implications for their future development and use in targeting ubiquitin-signaling pathways

NMR studies revealed structural basis for the inhibitory effects of ubistatins in the ubiquitin-mediated signaling pathways

International audienceUbiquitination is a critical protein post-translational modification involved in a variety of vital processes in eukaryotic cells. The discovery of ubistatins [1], small molecules that impair proteasomal degradation of proteins by directly binding to (poly)ubiquitin upstream of the proteasome, makes ubiquitin itself a potential therapeutic target. Although ubistatins have the potential for drug development and clinical applications, the lack of structural details of ubiquitin-ubistatin interactions has impeded their development. To address this deficiency, a panel of new ubistatin derivatives was synthesized and characterized using functional and NMR-based binding assays [2]. We found that the most active compounds contain strongly acidic groups. We then used NMR and small-angle neutron scattering (SANS) to determine the structures of ubiquitin complexes with ubistatin B and hemi-ubistatin B. These structures revealed direct interactions of ubistatins with ubiquitin’s hydrophobic surface-patch and the basic/polar residues surrounding it, which were confirmed by site-directed mutagenesis. Our results show that ubistatin B binds ubiquitin and di-ubiquitin tighter than a high-affinity ubiquitin-receptor, the UBA domain from the proteasomal shuttle protein ubiquilin-1, and shows clear preference for ubiquitin chains linked via K48 over those linked via K11 or K63. The 15N relaxation and SANS data revealed unexpected binding stoichiometries and structural arrangements of ubiquitin or di-ubiquitins in those complexes. Furthermore, through binding to ubiquitin, ubistatin B shields ubiquitin conjugates from disassembly by a range of deubiquitinases, including the 26S proteasome.Finally, we found that ubistatin B penetrates human cancer cells and perturbs the cellular ubiquitin landscape. These findings highlight versatile properties of ubistatins and have implications for their future development and use in targeting ubiquitin-mediated signaling pathways. Combined with the earlier observations that ubistatins can arrest the cell cycle, producing effects similar to proteasome inhibitors [1]), our structural data suggest that the ubiquitin signal is a plausible candidate for therapeutic intervention in the ubiquitin-proteasome pathway

Untersuchungen zur wasserstoffinduzierten Rissbildung im Schweissnahtbericht von Feinkornbaustahl bei low-cycle-Beanspruchung unter dem Einfluss von Druckwasserstoff Abschlussbericht

SIGLETIB: FR 4818 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

The Bad-Mad Dilemma for Public Psychiatry

Last September at St. Patrick’s Cathedral in New York City, a chronic mentally ill man bludgeoned an usher to death and injured a policeman before being killed by the police. This tragic incident underscores the dilemma faced by public psychiatry in its efforts to help seriously mentally ill individuals who are prone to violence while protecting their rights and the safety of the public. Once again, the media and the public questioned the mental health system’s ability to protect society from dangerous mentally ill persons. The news media traced the odyssey of the deranged man through numerous incarcerations and hospitalizations following violent actions. Certainly, monitoring of high-risk mentally ill patients is seriously handicapped by their continuous migration between the criminal justice and mental health systems. In New York City, as in other parts of the nation, these systems do not communicate with each other and are overwhelmed by an unprecedented number of inmates and patients. Police officers are permitted great discretion in their handling of socially disruptive people. As a result of the overcrowding in th

Who Profits From Deinstitutionalization

Deinstitutionalization, a euphemism for the massive and unplanned emptying of state psychiatric hospitals nationwide, has resulted in a reduction in the daily patient census from about 560,000 in 1955 t

Violent Behavior and Length of Hospitalization

Contributing Editors: Ian Alger, M.D., Audiovisuals Paul S. Appelbaum, M.D., Law & Psycbiatrj Leona L Bachrach, Ph.D., The Chronic Patient Gene D. Cohen, M.D., Ph.D., Practical Genatrics Spencer Eth, M.D. Ethics Allen Frances, M.D., Treatment Planning Martin Gittelman, Ph.D., Foreign Psychiatry Sheldon I. Miller, M.D., Akabol & Dneg Abuse Marilyn Sargent, NIMH Report Carl Salzman, M.D., Psychopharmacology Steven S. Sharfstein, M.D., &onomkGrandRounc