Charge Ordering and Phase Competition in the Layered Perovskite Lasr2mn2o7

Charge-lattice fluctuations are observed in the layered perovskite manganite LaSr2Mn2O7 by Raman spectroscopy as high as 340 K and with decreasing temperature they become static and form a charge ordered (CO) phase below TCO=210 K. In the static regime, superlattice reflections are observed through neutron and x-ray diffraction with a propagation vector (h+1/4,k-1/4,l). Crystallographic analysis of the CO state demonstrates that the degree of charge and orbital ordering in this manganite is weaker than the charge ordering in three dimensional perovskite manganites. A TN=170K a type-A antiferromagnetism (AF) develops and competes with the charge ordering, that eventually melts below T*=100K. High resolution diffraction measurements suggest that that CO- and AF-states do not coincide within the same region in the material but rather co-exist as separate phases. The transition to type-A antiferromagnetism at lower temperatures is characterized by the competition between these two phases.Comment: 9 pages, 6 figure

Systematic evaluation of an atomic clock at 2e-18 total uncertainty

The pursuit of better atomic clocks has advanced many research areas, providing better quantum state control, new insights in quantum science, tighter limits on fundamental constant variation, and improved tests of relativity. The record for the best stability and accuracy is currently held by optical lattice clocks. This work takes an important step towards realizing the full potential of a many-particle clock with a state-of-the-art stable laser. Our 87Sr optical lattice clock now achieves fractional stability of 2.2e-16 at 1 s. With this improved stability, we perform a new accuracy evaluation of our clock, reducing many systematic uncertainties that limited our previous measurements, such as those in the lattice ac Stark shift, the atoms' thermal environment, and the atomic response to room-temperature BBR. Our combined measurements have reduced the total uncertainty of the JILA Sr clock to 2.1e-18 in fractional frequency units.Comment: Full published versio

Bilateral giant abdominoscrotal hydroceles complicated by appendicitis

Abdominoscrotal hydrocele is a rare entity, with fewer than 100 cases reported in children. Bilateral abdominoscrotal hydroceles are even less common, with 14 cases reported in children. Various complications of abdominoscrotal hydrocele have been reported in the literature. We present a 4-month-old boy with bilateral giant abdominoscrotal hydrocele s who developed appendicitis apparently because of obstruction from the right hydrocele. We discuss the various imaging modalities used to establish the diagnosis and plan the operative approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46717/1/247_2005_Article_1572.pd

A Novel Flow Cytometric HTS Assay Reveals Functional Modulators of ATP Binding Cassette Transporter ABCB6

ABCB6 is a member of the adenosine triphosphate (ATP)-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS), can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6’s ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity

A Potent and Selective Inhibitor of Cdc42 GTPase

Cdc42, a member of the Rho family of GTPases, has been shown to play a role in cell adhesion, cytoskeletal arrangement, phagocytosis and cell motility and migration, in addition to a host of other diverse biological processes. The function of Rho-family GTPases in disease pathogenesis has been well established and identification of small, cell permeable molecules that selectively and reversibly regulate Rho GTPases is of high scientific and potentially therapeutic interest. There has been limited success in identifying inhibitors that specifically interact with small Rho family GTPases. The identified probe, ML141 (CID-2950007), is demonstrated to be a potent, selective and reversible non-competitive inhibitor of Cdc42 GTPase suitable for in vitro assays, with low micromolar potency and selectivity against other members of the Rho family of GTPases (Rac1, Rab2, Rab7). Given the highly complementary nature of the function of the Rho family GTPases, Cdc42 selective inhibitors such as those reported here should help untangle the roles of the proteins in this family

Lattice Displacements Above Tc in the Layered Manganite La1.2Sr1.8Mn2O7

Neutron diffraction data presented in this paper demonstrates the relevance of lattice displacement above TC, in our understanding of the evolution of the crystal structure with temperature in the layered CMR manganite La1.2Sr1.8Mn2O7. The anomalous temperature behavior of thermal diffuse scattering (TDS) in La1.2Sr1.8Mn2O7 strongly suggests that it arises from lattice displacements and correlates directly with anomalies in the displacement parameters of the O- and Mn-atoms and Mn-O bond lengths. From our measurements, the insulator - metal transition can be described as a transition from a high temperature state with disordered Mn-O bond lengths to a low temperature state with a more uniform distribution on Mn-O bonds. These observations are in agreement with polaronic charge transport above TC in the perovskite manganites; as electron hopping is responsible for bond disorder above TC, below the transition where eg carries are delocalized, any lattice displacements are uniformly averaged.Comment: 5 pages, 3 figures, submitted to Phys. Rev.

Characterization of a Cdc42 Protein Inhibitor and Its Use as a Molecular Probe

Cdc42 plays important roles in cytoskeleton organization, cell cycle progression, signal transduction, and vesicle trafficking. Overactive Cdc42 has been implicated in the pathology of cancers, immune diseases, and neuronal disorders. Therefore, Cdc42 inhibitors would be useful in probing molecular pathways and could have therapeutic potential. Previous inhibitors have lacked selectivity and trended toward toxicity. We report here the characterization of a Cdc42-selective guanine nucleotide binding lead inhibitor that was identified by high throughput screening. A second active analog was identified via structure-activity relationship studies. The compounds demonstrated excellent selectivity with no inhibition toward Rho and Rac in the same GTPase family. Biochemical characterization showed that the compounds act as noncompetitive allosteric inhibitors. When tested in cellular assays, the lead compound inhibited Cdc42-related filopodia formation and cell migration. The lead compound was also used to clarify the involvement of Cdc42 in the Sin Nombre virus internalization and the signaling pathway of integrin VLA-4. Together, these data present the characterization of a novel Cdc42-selective allosteric inhibitor and a related analog, the use of which will facilitate drug development targeting Cdc42-related diseases and molecular pathway studies that involve GTPases.This work was supported by National Science Foundation (NSF) Grant MCB0956027 and National Institutes of Health Grant R03 MH081231-01 from the Molecular Libraries Program (to A. W. N.); University of New Mexico Center for Molecular Discovery Molecular Libraries Probe Production Centers (UNMCMD MLPCN) National Institutes of Health Grants U54MH084690 and R01HL081062 (to L. A. S.); UNM National Center for Research Resources (NCRR) Grant 5P20RR016480 (to L. G. H.); National Institutes of Health Grant R21 CA170375-01 through the NCI (to A. W. N., L. G. H., and J. E. G.); National Institutes of Health Grants NS066429 and AI092130 (to T. B.); and University of Kansas Specialized Chemistry Center (KUSCC) MLPCN National Institutes of Health Grant U54HG005031 (to J. A.)