Discovery of structurally diverse natural product antagonists of chemokine receptor CXCR3

The chemokines (CXCL9, CXCL10 and CXCL11) and associated CXCR3 receptor are expressed during the inflammatory process from multiple sclerosis, atherosclerosis or organ transplantation resulting in the recruitment of lymphocytes leading to tissue damage. It is hypothesized that blocking of the ligand/CXCR3 receptor interaction has potential to provide opportunity for development of agents that would block tissue rejection. In this paper, four classes of natural product inhibitors (IC₅₀ ranging 0.1–41 M) have been described that block the CXCR3 receptor interaction of IP-10 ligand. These include a cyclic thiopeptide (duramycin), polyketide glycosides (roselipins), steroidal glycosides (hypoglausin A and dioscin) and a novel alkyl pyridinium alkaloid that were isolated by bioassay-guided fractionation of the organic extracts derived from actinomycete, fungal, plant and marine sources and discovered using ¹²⁵ I IP-10/CXCR3 binding assay. Duramycin was the most potent with an IC₅₀ of 0.1 M. Roselipins 2A, 2B and 1A showed IC₅₀ values of 14.6, 23.5, and 41 M, respectively. Diosgenin glycosides dioscin, hypoglaucin A and kallstroemin D exhibited IC₅₀ values of 2.1, 0.47 and 3 M, respectively. A novel cyclic 3-alkyl pyridinium salt isolated from a sponge displayed a binding IC₅₀ of 0.67 M.     

The puzzle of contrast inversion in DNA STM imaging

DNA has been at the center of an imaging effort since the invention of the scanning tunneling microscope (STM). In some of the STM imaging reports the molecules appeared with negative contrast, i.e., "submerged" under the metal background and darker. We demonstrate the phenomenon of contrast inversion in DNA STM imaging by controlled and spontaneous contrast inversions and by the dependence of the DNA apparent height with respect to the surface on the imaging bias voltage. Using these characterizations, we formulate a model explaining the above phenomenon by resonant tunneling through virtual states in the vacuum between the STM tip and the DNA molecule.     

Bundle Gerbes for Chern-Simons and Wess-Zumino-Witten Theories

We develop the theory of Chern-Simons bundle 2-gerbes and multiplicative bundle gerbes associated to any principal G-bundle with connection and a class in H⁴(BG, ℤ) for a compact semi-simple Lie group G. The Chern-Simons bundle 2-gerbe realises differential geometrically the Cheeger-Simons invariant. We apply these notions to refine the Dijkgraaf-Witten correspondence between three dimensional Chern-Simons functionals and Wess-Zumino-Witten models associated to the group G. We do this by introducing a lifting to the level of bundle gerbes of the natural map from H⁴(BG, ℤ) to H³(G, ℤ). The notion of a multiplicative bundle gerbe accounts geometrically for the subtleties in this correspondence for non-simply connected Lie groups. The implications for Wess-Zumino-Witten models are also discussed.The authors acknowledge the support of the Australian Research Council. ALC thanks MPI für Mathematik in Bonn and ESI in Vienna and BLW thanks CMA of Australian National University for their hospitality during part of the writing of this paper.     

Evidence for high-efficiency laser-heated hohlraum performance at 527 nm

A series of experiments conducted on the HELEN laser system [M. J. Norman, Appl. Opt.4120023497], into thermal x-ray generation from hohlraum targets using 527 nm (2omega) wavelength laser light, has shown that it is possible to exceed radiation temperatures previously thought limited by high levels of superthermal or hot electron production or stimulated backscatter. This Letter questions whether the assumptions traditionally applied to hohlraum design with respect to hot plasma filling and the use of 2omega light are too conservative.     

Mechanistic investigation leads to a synthetic improvement in the hydrolytic kinetic resolution of terminal epoxides

The mechanism of the hydrolytic kinetic resolution (HKR) of terminal epoxides was investigated by kinetic analysis using reaction calorimetry. The chiral (salen)Co-X complex (X = OAc, OTs, Cl) undergoes irreversible conversion to (salen)Co-OH during the course of the HKR and thus serves as both precatalyst and cocatalyst in a cooperative bimetallic catalytic mechanism. This insight led to the identification of more active catalysts for the HKR of synthetically useful terminal epoxides.     

Chern Character in Twisted K-Theory: Equivariant and Holomorphic Cases

 It was argued in [25, 5] that in the presence of a nontrivial B-field, D-brane charges in type IIB string theories are classified by twisted K-theory. In [4], it was proved that twisted K-theory is canonically isomorphic to bundle gerbe K-theory, whose elements are ordinary Hilbert bundles on a principal projective unitary bundle, with an action of the bundle gerbe determined by the principal projective unitary bundle. The principal projective unitary bundle is in turn determined by the twist. This paper studies in detail the Chern-Weil representative of the Chern character of bundle gerbe K-theory that was introduced in [4], extending the construction to the equivariant and the holomorphic cases. Included is a discussion of interesting examples. Received: 10 January 2002 / Accepted: 9 December 2002 Published online: 25 February 2003 RID="⋆" ID="⋆" The authors acknowledge the support of the Australian Research Council Communicated by R.H. Dijkgraaf     

Efficient Regular Polygon Dissections

We study the minimum number g(m,n) (respectively, p(m,n)) of pieces needed to dissect a regular m-gon into a regular n-gon of the same area using glass-cuts (respectively, polygonal cuts). First we study regular polygon-square dissections and show that n/2 -2 g(4,n) (n/2) + o(n) and n/4 g(n,4) (n/2) + o(n) hold for sufficiently large n. We also consider polygonal cuts, i.e., the minimum number p(4,n) of pieces needed to dissect a square into a regular n-gon of the same area using polygonal cuts and show that n/4 p(4,n) (n/2) + o(n) holds for sufficiently large n. We also consider regular polygon-polygon dissections and obtain similar bounds for g(m,n) and p(m,n).     

Cross section for b-Jet production in &pmacr;p collisions at radicals = 1.8 TeV

Bottom-quark production in &pmacr;p collisions at sqrt[s] = 1.8 TeV is studied with 5 pb(-1) of data collected in 1995 by the D0 detector at the Fermilab Tevatron Collider. The differential production cross section for b jets in the central rapidity region ( | y(b)|<1) as a function of jet transverse energy is extracted from a muon-tagged jet sample. Within experimental and theoretical uncertainties, D0 results are found to be higher than, but compatible with, next-to-leading-order QCD predictions.     

Spin correlation in t&tmacr; production from p&pmacr; collisions at radicals = 1.8 TeV

The D0 collaboration has performed a study of spin correlation in t&tmacr; production for the process t&tmacr;-->bW(+)&bmacr;W-, where the W bosons decay to enu or &mgr;nu. A sample of six events was collected during an exposure of the D0 detector to an integrated luminosity of approximately 125 pb(-1) of sqrt[s] = 1.8 TeV p&pmacr; collisions. The standard model (SM) predicts that the short lifetime of the top quark ensures the transmission of any spin information at production to the t&tmacr; decay products. The degree of spin correlation is characterized by a correlation coefficient kappa. We find that kappa>-0.25 at the 68% confidence level, in agreement with the SM prediction of kappa = 0.88.     

Angle-resonant stimulated polariton amplifier

We experimentally demonstrate resonant coupling between photons and excitons in microcavities which can efficiently generate enormous single-pass optical gains approaching 100. This new parametric phenomenon appears as a sharp angular resonance of the incoming pump beam, at which the moving excitonic polaritons undergo very large changes in momentum. Ultrafast stimulated scattering is clearly identified from the exponential dependence on pump intensity. This device utilizes boson amplification induced by stimulated energy relaxation.