A monoclonal antibody recognizing very late activation antigen-4 inhibits eosinophil accumulation in vivo.

Using an in vivo test system, the role of the β1 integrin very late activation antigen-4 (VLA-4) in eosinophil accumulation in allergic and nonallergic inflammatory reactions was investigated. Eosinophil infiltration and edema formation were measured as the local accumulation of intravenously injected 111In-labeled eosinophils and 125I-human serum albumin. The inflammatory reactions investigated were a passive cutaneous anaphylaxis (PCA) reaction and responses elicited by intradermal soluble inflammatory mediators (platelet-activating factor, leukotriene B4, C5a des Arg), arachidonic acid, and zymosan particles. The in vitro pretreatment of 111In-eosinophils with the anti-VLA-4 monoclonal antibody (mAb) HP1/2, which crossreacts with guinea pig eosinophils, suppressed eosinophil accumulation in all the inflammatory reactions investigated. Eosinophil accumulation was inhibited to the same extent when mAb HP1/2 was administered intravenously. It is interesting that HP1/2 had no effect on stimulated edema formation. These results suggest a role for VLA-4 in eosinophil accumulation in vivo and indicate a dissociation between the inflammatory events of eosinophil accumulation and edema formation

Improved mapping functions for atmospheric refraction correction in SLR

[1] We present two new mapping functions (MFs) to model the elevation angle dependence of the atmospheric delay for satellite laser ranging (SLR) data analysis. The new MFs were derived from ray tracing through a set of data from 180 radiosonde stations globally distributed, for the year 1999, and are valid for elevation angles above 3degrees. When compared against ray tracing of two independent years of radiosonde data (1997-1998) for the same set of stations, our MFs reveal submillimetre accuracy for elevation angles above 10degrees, representing a significant improvement over other MFs, and is confirmed in improved solutions of LAGEOS and LAGEOS 2 data analysis.info:eu-repo/semantics/publishedVersio

E. coli surface display of streptavidin for directed evolution of an allylic deallylase

Artificial metalloenzymes (ArMs hereafter) combine attractive features of both homogeneous catalysts and enzymes and offer the potential to implement new-to-nature reactions in living organisms. Herein we present an E. coli surface display platform for streptavidin (Sav hereafter) relying on an Lpp-OmpA anchor. The system was used for the high throughput screening of a bioorthogonal CpRu-based artificial deallylase (ADAse) that uncages an allylcarbamate-protected aminocoumarin 1. Two rounds of directed evolution afforded the double mutant S112M–K121A that displayed a 36-fold increase in surface activity vs. cellular background and a 5.7-fold increased in vitro activity compared to the wild type enzyme. The crystal structure of the best ADAse reveals the importance of mutation S112M to stabilize the cofactor conformation inside the protein

Genetic characterization of human coxsackievirus A6 variants associated with atypical hand, foot and mouth disease: a potential role of recombination in emergence and pathogenicity

Human coxsackievirus A6 (CVA6) is an enterically transmitted enterovirus. Until recently, CVA6 infections were considered as being of minor clinical significance, and only rarely aetiologically linked with hand, foot and mouth disease (HFMD) associated with other species A enteroviruses (particularly EV71 and CVA16). From 2008 onwards, however, CVA6 infections have been associated with several outbreaks worldwide of atypical HFMD (aHFMD) accompanied by a varicelliform rash. We recently reported CVA6-associated eczema herpeticum occurring predominantly in children and young adults in Edinburgh in January and February 2014. To investigate genetic determinants of novel clinical phenotypes of CVA6, we genetically characterized and analysed CVA6 variants associated with eczema herpeticum in Edinburgh in 2014 and those with aHFMD in CAV isolates collected from 2008. A total of eight recombinant forms (RFs) have circulated worldwide over the past 10 years, with the particularly recent appearance of RF-H associated with eczema herpeticum cases in Edinburgh in 2014. Comparison of phylogenies and divergence of complete genome sequences of CVA6 identified recombination breakpoints in 2A-2C, within VP3, and between 5' untranslated region and VP1. A Bayesian temporal reconstruction of CVA6 evolution since 2004 provided estimates of dates and the actual recombination events that generated more recently appearing recombination groups (RF-E, -F, -G and -H). Associations were observed between recombination groups and clinical presentations of herpangina, aHFMD and eczema herpeticum, but not with VP1 or other structural genes. These observations provided evidence that NS gene regions may potentially contribute to clinical phenotypes and outcomes of CVA6 infection

Light trapping in high-density ultracold atomic gases for quantum memory applications

High-density and ultracold atomic gases have emerged as promising media for storage of individual photons for quantum memory applications. In this paper we provide an overview of our theoretical and experimental efforts in this direction, with particular attention paid to manipulation of light storage (a) through complex recurrent optical scattering processes in very high density gases (b) by an external control field in a characteristic electromagnetically induced transparency configuration.Comment: Submitted to Journal of Modern Optics, Special 2010 PQE Issu

Algorithms for outerplanar graph roots and graph roots of pathwidth at most 2

Deciding whether a given graph has a square root is a classical problem that has been studied extensively both from graph theoretic and from algorithmic perspectives. The problem is NP-complete in general, and consequently substantial effort has been dedicated to deciding whether a given graph has a square root that belongs to a particular graph class. There are both polynomial-time solvable and NP-complete cases, depending on the graph class. We contribute with new results in this direction. Given an arbitrary input graph G, we give polynomial-time algorithms to decide whether G has an outerplanar square root, and whether G has a square root that is of pathwidth at most 2

Microsecond Time-Resolved Absorption Spectroscopy Used to Study CO Compounds of Cytochrome bd from Escherichia coli

Cytochrome bd is a tri-heme (b558, b595, d) respiratory oxygen reductase that is found in many bacteria including pathogenic species. It couples the electron transfer from quinol to O2 with generation of an electrochemical proton gradient. We examined photolysis and subsequent recombination of CO with isolated cytochrome bd from Escherichia coli in oneelectron reduced (MV) and fully reduced (R) states by microsecond time-resolved absorption spectroscopy at 532-nm excitation. Both Soret and visible band regions were examined. CO photodissociation from MV enzyme possibly causes fast (t,1.5 ms) electron transfer from heme d to heme b595 in a small fraction of the protein, not reported earlier. Then the electron migrates to heme b558 (t,16 ms). It returns from the b-hemes to heme d with t,180 ms. Unlike cytochrome bd in the R state, in MV enzyme the apparent contribution of absorbance changes associated with CO dissociation from heme d is small, if any. Photodissociation of CO from heme d in MV enzyme is suggested to be accompanied by the binding of an internal ligand (L) at the opposite side of the heme. CO recombines with heme d (t,16 ms) yielding a transient hexacoordinate state (CO-Fe2+ -L). Then the ligand slowly (t,30 ms) dissociates from heme d. Recombination of CO with a reduced heme b in a fraction of the MV sample may also contribute to the 30-ms phase. In R enzyme, CO recombines to heme d (t,20 ms), some heme b558 (t,0.2–3 ms), and finally migrates from heme d to heme b595 (t,24 ms) in ,5% of the enzyme population. Data are consistent with the recent nanosecond study of Rappaport et al. conducted on the membranes at 640-nm excitation but limited to the Soret band. The additional phases were revealed due to differences in excitation and other experimental conditions

Uhlenbeck-Donaldson compactification for framed sheaves on projective surfaces

We construct a compactification $M^{\mu ss}$ of the Uhlenbeck-Donaldson type for the moduli space of slope stable framed bundles. This is a kind of a moduli space of slope semistable framed sheaves. We show that there exists a projective morphism $\gamma \colon M^{ss} \to M^{\mu ss}$, where $M^{ss}$ is the moduli space of S-equivalence classes of Gieseker-semistable framed sheaves. The space $M^{\mu ss}$ has a natural set-theoretic stratification which allows one, via a Hitchin-Kobayashi correspondence, to compare it with the moduli spaces of framed ideal instantons.Comment: 18 pages. v2: a few very minor changes. v3: 27 pages. Several proofs have been considerably expanded, and more explanations have been added. v4: 28 pages. A few minor changes. Final version accepted for publication in Math.