420 research outputs found

    The Ursinus Weekly, February 24, 1977

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    Ursinus news in brief: Weekly to accept applications; Poli. Sci. Washington trip; Ursinus to exhibit frakturs; More on absenteeism; Pre Legal meets • U.S.G.A. election results • Wismer, sunshine discussed • James Craft interviewed • Dining hall probed • Letters to the editor: Information please!; TGV and South Africa • Wild blue yonder • ELO Lives!! • Cassandra • Denenberg speaks • Photos • Immaculata here tonight • Up for the match • Swimming bare machine rolls on, but men lose • Elsewhere in UC sports scenehttps://digitalcommons.ursinus.edu/weekly/1066/thumbnail.jp

    Extending Halogen-based Medicinal Chemistry to Proteins: IODO-INSULIN AS A CASE STUDY

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    Insulin, a protein critical for metabolic homeostasis, provides a classical model for protein design with application to human health. Recent efforts to improve its pharmaceutical formulation demonstrated that iodination of a conserved tyrosine (Tyr(B26)) enhances key properties of a rapid-acting clinical analog. Moreover, the broad utility of halogens in medicinal chemistry has motivated the use of hybrid quantum- and molecular-mechanical methods to study proteins. Here, we (i) undertook quantitative atomistic simulations of 3-[iodo-Tyr(B26)]insulin to predict its structural features, and (ii) tested these predictions by X-ray crystallography. Using an electrostatic model of the modified aromatic ring based on quantum chemistry, the calculations suggested that the analog, as a dimer and hexamer, exhibits subtle differences in aromatic-aromatic interactions at the dimer interface. Aromatic rings (Tyr(B16), Phe(B24), Phe(B25), 3-I-Tyr(B26), and their symmetry-related mates) at this interface adjust to enable packing of the hydrophobic iodine atoms within the core of each monomer. Strikingly, these features were observed in the crystal structure of a 3-[iodo-Tyr(B26)]insulin analog (determined as an R6 zinc hexamer). Given that residues B24-B30 detach from the core on receptor binding, the environment of 3-I-Tyr(B26) in a receptor complex must differ from that in the free hormone. Based on the recent structure of a "micro-receptor" complex, we predict that 3-I-Tyr(B26) engages the receptor via directional halogen bonding and halogen-directed hydrogen bonding as follows: favorable electrostatic interactions exploiting, respectively, the halogen's electron-deficient σ-hole and electronegative equatorial band. Inspired by quantum chemistry and molecular dynamics, such "halogen engineering" promises to extend principles of medicinal chemistry to proteins

    On the Decoupling of Layered Superconducting Films in Parallel Magnetic Field

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    The issue of the decoupling of extreme type-II superconducting thin films (λL→∞\lambda_L\rightarrow\infty) with weakly Josephson-coupled layers in magnetic field parallel to the layers is considered via the corresponding frustrated XYXY model used to describe the mixed phase in the critical regime. For the general case of arbitrary field orientations such that the perpendicular magnetic field component is larger than the decoupling cross-over scale characteristic of layered superconductors, we obtain independent parallel and perpendicular vortex lattices. Specializing to the double-layer case, we compute the parallel lower-critical field with entropic effects included, and find that it vanishes exponentially as temperature approaches the layer decoupling transition in zero-field. The parallel reversible magnetization is also calculated in this case, where we find that it shows a cross-over phenomenon as a function of parallel field in the intermediate regime of the mixed phase in lieu of a true layer-decoupling transition. It is argued that such is the case for any finite number of layers, since the isolated double layer represents the weakest link.Comment: 29 pages of plain TeX, 2 postscript figures, improved discussio

    The Ursinus Weekly, February 9, 1977

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    Ursinus news in brief: Summer employment outlook; Temple adopts plus, minus grades; U.S.G.A. releases absenteeism data; Craft named exec. assistant • Cafeteria trials successful • Testing rule changed • Calendar to be reviewed • S.F.A.R.C. discusses counseling, vandalism • Comment: A short lesson in Weekly economics • Ursinus: a suburban wasteland • Our common cause • Transcript hassles • Forum review: Musical notes • Let\u27s line up for Wismer • TGV • Seniors plan dinner dance • Art exhibition • Pre-Legal group meets • Basketball loses again • Commentary: Is a new coach needed? • Swimming teams resume seasons • Wrestling wrap-uphttps://digitalcommons.ursinus.edu/weekly/1065/thumbnail.jp

    N=4 Superconformal Algebra and the Entropy of HyperKahler Manifolds

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    We study the elliptic genera of hyperKahler manifolds using the representation theory of N=4 superconformal algebra. We consider the decomposition of the elliptic genera in terms of N=4 irreducible characters, and derive the rate of increase of the multiplicities of half-BPS representations making use of Rademacher expansion. Exponential increase of the multiplicity suggests that we can associate the notion of an entropy to the geometry of hyperKahler manifolds. In the case of symmetric products of K3 surfaces our entropy agrees with the black hole entropy of D5-D1 system.Comment: 25 pages, 1 figur

    Open string wavefunctions in flux compactifications

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    We consider compactifications of type I supergravity on manifolds with SU(3) structure, in the presence of RR fluxes and magnetized D9-branes, and analyze the generalized Dirac and Laplace-Beltrami operators associated to the D9-brane worldvolume fields. These compactifications are T-dual to standard type IIB toroidal orientifolds with NSNS and RR 3-form fluxes and D3/D7 branes. By using techniques of representation theory and harmonic analysis, the spectrum of open string wavefunctions can be computed for Lie groups and their quotients, as we illustrate with explicit twisted tori examples. We find a correspondence between irreducible unitary representations of the Kaloper-Myers algebra and families of Kaluza-Klein excitations. We perform the computation of 2- and 3-point couplings for matter fields in the above flux compactifications, and compare our results with those of 4d effective supergravity.Comment: 89 pages, 4 figures. v3: more typos corrected, version published in JHE

    An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein

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    Thermal degradation of insulin complicates its delivery and use. Previous efforts to engineer ultra-stable analogs were confounded by prolonged cellular signaling in vivo, of unclear safety and complicating mealtime therapy. We therefore sought an ultra-stable analog whose potency and duration of action on intravenous bolus injection in diabetic rats are indistinguishable from wild-type (WT) insulin. Here, we describe the structure, function, and stability of such an analog, a 57-residue single-chain insulin (SCI) with multiple acidic substitutions. Cell-based studies revealed native-like signaling properties with negligible mitogenic activity. Its crystal structure, determined as a novel zinc-free hexamer at 2.8 Å, revealed a native insulin fold with incomplete or absent electron density in the C domain; complementary NMR studies are described in the accompanying article. The stability of the analog (ΔGU 5.0(±0.1) kcal/mol at 25 °C) was greater than that of WT insulin (3.3(±0.1) kcal/mol). On gentle agitation, the SCI retained full activity for >140 days at 45 °C and >48 h at 75 °C. These findings indicate that marked resistance to thermal inactivation in vitro is compatible with native duration of activity in vivo Further, whereas WT insulin forms large and heterogeneous aggregates above the standard 0.6 mm pharmaceutical strength, perturbing the pharmacokinetic properties of concentrated formulations, dynamic light scattering, and size-exclusion chromatography revealed only limited SCI self-assembly and aggregation in the concentration range 1-7 mm Such a combination of favorable biophysical and biological properties suggests that SCIs could provide a global therapeutic platform without a cold chain
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