Distributional Modes for Scalar Field Quantization

We propose a mode-sum formalism for the quantization of the scalar field based on distributional modes, which are naturally associated with a slight modification of the standard plane-wave modes. We show that this formalism leads to the standard Rindler temperature result, and that these modes can be canonically defined on any Cauchy surface.Comment: 15 pages, RevTe

Iterative in Situ Click Chemistry Assembles a Branched Capture Agent and Allosteric Inhibitor for Akt1

We describe the use of iterative in situ click chemistry to design an Akt-specific branched peptide triligand that is a drop-in replacement for monoclonal antibodies in multiple biochemical assays. Each peptide module in the branched structure makes unique contributions to affinity and/or specificity resulting in a 200 nM affinity ligand that efficiently immunoprecipitates Akt from cancer cell lysates and labels Akt in fixed cells. Our use of a small molecule to preinhibit Akt prior to screening resulted in low micromolar inhibitory potency and an allosteric mode of inhibition, which is evidenced through a series of competitive enzyme kinetic assays. To demonstrate the efficiency and selectivity of the protein-templated in situ click reaction, we developed a novel QPCR-based methodology that enabled a quantitative assessment of its yield. These results point to the potential for iterative in situ click chemistry to generate potent, synthetically accessible antibody replacements with novel inhibitory properties

G_2 Perfect-Fluid Cosmologies with a proper conformal Killing vector

We study the Einstein field equations for spacetimes admitting a maximal two-dimensional abelian group of isometries acting orthogonally transitively on spacelike surfaces and, in addition, with at least one conformal Killing vector. The three-dimensional conformal group is restricted to the case when the two-dimensional abelian isometry subalgebra is an ideal and it is also assumed to act on non-null hypersurfaces (both, spacelike and timelike cases are studied). We consider both, diagonal and non-diagonal metrics and find all the perfect-fluid solutions under these assumptions (except those already known). We find four families of solutions, each one containing arbitrary parameters for which no differential equations remain to be integrated. We write the line-elements in a simplified form and perform a detailed study for each of these solutions, giving the kinematical quantities of the fluid velocity vector, the energy-density and pressure, values of the parameters for which the energy conditions are fulfilled everywhere, the Petrov type, the singularities in the spacetimes and the Friedmann-Lemaitre-Robertson-Walker metrics contained in each family.Comment: Latex, no figure

In situ click chemistry: from small molecule discovery to synthetic antibodies

Advances in the fields of proteomics, molecular imaging, and therapeutics are closely linked to the availability of affinity reagents that selectively recognize their biological targets. Here we present a review of Iterative Peptide In Situ Click Chemistry (IPISC), a novel screening technology for designing peptide multiligands with high affinity and specificity. This technology builds upon in situ click chemistry, a kinetic target-guided synthesis approach where the protein target catalyzes the conjugation of two small molecules, typically through the azide–alkyne Huisgen cycloaddition. Integrating this methodology with solid phase peptide libraries enables the assembly of linear and branched peptide multiligands we refer to as Protein Catalyzed Capture Agents (PCC Agents). The resulting structures can be thought of as analogous to the antigen recognition site of antibodies and serve as antibody replacements in biochemical and cell-based applications. In this review, we discuss the recent progress in ligand design through IPISC and related approaches, focusing on the improvements in affinity and specificity as multiligands are assembled by target-catalyzed peptide conjugation. We compare the IPISC process to small molecule in situ click chemistry with particular emphasis on the advantages and technical challenges of constructing antibody-like PCC Agents

Uterine Mast Cells and Immunoglobulin-E Antibody Responses During Clearance of \u3ci\u3eTritrichomonas foetus\u3c/i\u3e

We showed earlier that Tritrichomonas foetus–specific bovine immunoglobulin (Ig)G1 and IgA antibodies in uterine and vaginal secretions are correlated with clearance of this sexually transmitted infection. Eosinophils have been noted in previous studies of bovine trichomoniasis but the role of mast cells and IgE responses have not been reported. The hypothesis that IgE and mast cell degranulation play a role in clearance was tested in 25 virgin heifers inseminated experimentally and infected intravaginally with T. foetus strain D1 at estrus and cultured weekly. Groups were euthanatized at 3, 6, 9, or 12 weeks, when tissues were fixed and secretions were collected for culture and antibody analysis. Immunohistochemistry using a monoclonal antibody to a soluble lipophosphoglycan (LPG)–containing surface antigen (TF1.17) demonstrated antigen uptake by uterine epithelial cells. Lymphoid nodules were detected below antigen-positive epithelium. Little IgG2 antibody was detected but IgG1, IgA, IgM, and IgE T. foetus–specific antibodies increased in uterine secretions at weeks 6 and 9 after infection. This was inversely proportional to subepithelial mast cells numbers and most animals cleared the infection by the sampling time after the lowest mast cell count. Furthermore, soluble antigen was found in uterine epithelium above inductive sites (lymphoid nodules). Cross-linking of IgE on mast cells by antigen and perhaps LPG triggering appears to have resulted in degranulation. Released cytokines may account for production of predominantly Th2 (IgG1 and IgE) and IgA antibody responses, which are related to clearance of the infection

Top quark physics in hadron collisions

The top quark is the heaviest elementary particle observed to date. Its large mass makes the top quark an ideal laboratory to test predictions of perturbation theory concerning heavy quark production at hadron colliders. The top quark is also a powerful probe for new phenomena beyond the Standard Model of particle physics. In addition, the top quark mass is a crucial parameter for scrutinizing the Standard Model in electroweak precision tests and for predicting the mass of the yet unobserved Higgs boson. Ten years after the discovery of the top quark at the Fermilab Tevatron top quark physics has entered an era where detailed measurements of top quark properties are undertaken. In this review article an introduction to the phenomenology of top quark production in hadron collisions is given, the lessons learned in Tevatron Run I are summarized, and first Run II results are discussed. A brief outlook to the possibilities of top quark research a the Large Hadron Collider, currently under construction at CERN, is included.Comment: 84 pages, 32 figures, accepted for publication by Reports on Progress in Physic

Atomic-scale modeling of the deformation of nanocrystalline metals

Nanocrystalline metals, i.e. metals with grain sizes from 5 to 50 nm, display technologically interesting properties, such as dramatically increased hardness, increasing with decreasing grain size. Due to the small grain size, direct atomic-scale simulations of plastic deformation of these materials are possible, as such a polycrystalline system can be modeled with the computational resources available today. We present molecular dynamics simulations of nanocrystalline copper with grain sizes up to 13 nm. Two different deformation mechanisms are active, one is deformation through the motion of dislocations, the other is sliding in the grain boundaries. At the grain sizes studied here the latter dominates, leading to a softening as the grain size is reduced. This implies that there is an ``optimal'' grain size, where the hardness is maximal. Since the grain boundaries participate actively in the deformation, it is interesting to study the effects of introducing impurity atoms in the grain boundaries. We study how silver atoms in the grain boundaries influence the mechanical properties of nanocrystalline copper.Comment: 10 pages, LaTeX2e, PS figures and sty files included. To appear in Mater. Res. Soc. Symp. Proc. vol 538 (invited paper). For related papers, see http://www.fysik.dtu.dk/~schiotz/publist.htm