Asymptotic behavior for a viscous Hamilton-Jacobi equation with critical exponent

The large time behavior of non-negative solutions to the viscous Hamilton-Jacobi equation $u_t - \Delta u + |\nabla u|^q = 0$ in the whole space $R^N$ is investigated for the critical exponent $q = (N+2)/(N+1)$. Convergence towards a rescaled self-similar solution of the linear heat equation is shown, the rescaling factor being $(\log(t))^{-(N+1)}$. The proof relies on the construction of a one-dimensional invariant manifold for a suitable truncation of the equation written in self-similar variables.Comment: 17 pages, no figur

Cyclophilin-A is bound to through its peptidylprolyl isomerase domain to the cytoplasmic dynein motor protein complex

Although cyclophilin A (CyP-A) is a relatively abundant small immunophilin present in the cytoplasm of all mammalian cells, its general function(s) in the absence of the immunosuppressant drug cyclosporin A is not known. In contrast, the high molecular weight hsp90-binding immunophilins appear to play a role in protein trafficking in that they have been shown to link glucocorticoid receptor-hsp90 and p53.hsp90 complexes to the dynein motor protein for retrograde movement along microtubules. These immunophilins link to cytoplasmic dynein indirectly through the association of the immunophilin peptidylprolyl isomerase (PPIase) domain with dynamitin, a component of the dynein-associated dynactin complex (Galigniana, M. D., Harrell, J. M., O'Hagen, H. M., Ljungman, M., and Pratt, W. B. (2004) J. Biol. Chem. 279, 22483-22489). Here, we show that CyP-A exists in native heterocomplexes containing cytoplasmic dynein that can be formed in cell-free systems. Prolyl isomerase activity is not required for forming the dynein complex, but the PPIase domain fragment of FKBP52 blocks complex formation and CyP-A binds to dynamitin in a PPIase domain-dependent manner. CyP-A heterocomplexes containing tubulin and dynein can be formed in cytosol prepared under microtubule-stabilizing conditions, and CyP-A colocalizes in mouse fibroblasts with microtubules. Colocalization with microtubules is disrupted by overexpression of the PPIase domain fragment. Thus, we conclude that CyP-A associates in vitro and in vivo with the dynein/dynactin motor protein complex and we suggest that CyP-A may perform a general function related to the binding of cargo for retrograde movement along microtubules.Fil: Galigniana, Mario Daniel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Michigan; Estados UnidosFil: Morishima, Yoshihiro. University of Michigan; Estados UnidosFil: Gallay, Philippe A.. The Scripps Research Institute; Estados UnidosFil: Pratt, William B.. University of Michigan; Estados Unido

Review of the twelfth West Coast retrovirus meeting

Every year the Cancer Research Institute from University of California at Irvine organizes the West Coast Retrovirus Meeting where participants have a chance to discuss the latest progress in understanding the pathology of retroviruses. The 12(th )meeting was held at the Hyatt Regency Suites in Palm Springs, California from October 6(th )to October 9(th )2005, with the major focus on human immunodeficiency virus (HIV) pathogenesis. Philippe Gallay from The Scripps Research Institute and Thomas J. Hope from Northwestern University organized the meeting, which covered all the steps involved in the lifecycle of retroviruses with an emphasis on virus:host interactions. The trend in research appeared to be on the restriction of viral infection, both by the endogenous, cellular restriction factors, as well as by the potential antimicrobial compounds of known or unknown mechanisms. Additionally, new stories on the inevitable feedback from the host immune system were presented as well. HIV still represents a challenge that an army of motivated people has been working on for over 20 years. And yet, the field has not reached the plateau in knowledge nor enthusiasm, which was proven again in October 2005 in Palm Springs

Bactericidal/Permeability-Increasing Protein Inhibits Induction of Macrophage Nitric Oxide Production by Lipopolysaccharide

A recombinant (r) NH2-terminal fragment of bactericidal/permeability-increasing protein, rBPI23, was shown to inhibit murine macrophage nitric oxide (NO) production elicited by lipopolysaccharide (LPS) plus interferon-β (IFN-β). Normal mouse plasma amplified NO synthesis (measured as NO-2 release) at LPS concentrations of 1-10 ng/mL, and antibody to the plasma LPS-binding protein (LBP) partially inhibited N02 release in the presence of normal mouse plasma. rBPI23 (1 µg/mL) effectively inhibited LPS-dependent NO-2 release in the presence or absence of normal mouse plasma. Fifty percent inhibition of IFN-β/LPS-elicited NO-2 production or of binding of fluoresceinated LPS was obtained with ∼0.2 µg/mL rBPI23. These results provide a basis for studies of rBPI23 effects on NO synthase activity in murine models of gramnegative sepsi

Lipopolysaccharide (LPS)-Binding Protein In Human Serum Determines The Tumor Necrosis Factor Response Of Monocytes To LPS

Lipopolysaccharide (LPS)-binding protein (LBP) and CD14 represent key elements in monocyte activation by LPS. The mean concentration of LBP was 18.1 µg/mL in normal serum and 40-60 µg/mL in serum of patients with septic shock, independent of the fact that patients had gram-negative or other infections. Ten percent normal serum presented large concentrations of LPS (in the microgram range) to monocytes. Only when diluted 1:100 was LBP in plasma a limiting factor for monocyte activation, as measured by tumor necrosis factor (TNF) release. When LBP was depleted from serum with anti-LBP antibodies, the resulting serum did not support TNF release of monocytes upon LPS challenge. In conclusion, monocyte activation resulting in TNF secretion was related to LBP, which is abundantly present in normal serum, and elevated two to three times in patients with septic shoc

Competition between Bactericidal/Permeability-Increasing Protein and Lipopolysaccharide-Binding Protein for Lipopolysaccharide Binding to Monocytes

The bactericidal/permeability-increasing protein (BPI) inhibits the lipopolysaccharide (LPS)mediated activation of monocytes. Due to its inhibitory activity for various LPS, BPI has therapeutic potential in endotoxic shock. To be efficient in vivo, BPI should overcome the action of LPS-binding protein (LBP), a serum molecule that increases the expression of LPS-inducible genes via CD 14 of monocytes. rBPI23, a recombinant fragment of BPI, prevented in a dose-dependent manner the binding and the internalization of LPS mediated by LBP. Consequently, rBPI23 also inhibited LPS-induced tumor necrosis factor (TNFα) synthesis from monocytes. LPS- and LBP-mediated activation of monocytes was totally inhibited when LPS was preincubated with rBPI23. Adding rBPI23 at the same time as LBP resulted in an important but partial inhibition of TNFα release, but this inhibition vanished with delaying the time of addition of rBPI23. These studies suggest that the inhibitory activity of BPI is related to its ability to compete with LBP for LP

PD 404,182 Is a Virocidal Small Molecule That Disrupts Hepatitis C Virus and Human Immunodeficiency Virus

We describe a virucidal small molecule, PD 404,182, that is effective against hepatitis C virus (HCV) and human immunodeficiency virus (HIV). The median 50% inhibitory concentrations (IC(50)s) for the antiviral effect of PD 404,182 against HCV and HIV in cell culture are 11 and 1 μM, respectively. The antiviral activity of PD 404,182 is due to the physical disruption of virions that is accompanied to various degrees (depending on the virus and exposure temperature/time) by the release of viral nucleic acids into the surrounding medium. PD 404,182 does not directly lyse liposomal membranes even after extended exposure, and it shows no attenuation in antiviral activity when preincubated with liposomes of various lipid compositions, suggesting that the compound inactivates viruses through interaction with a nonlipid structural component of the virus. The virucidal activity of PD 404,182 appears to be virus specific, as little to no viral inactivation was detected with the enveloped Dengue and Sindbis viruses. PD 404,182 effectively inactivates a broad range of primary isolates of HIV-1 as well as HIV-2 and simian immunodeficiency virus (SIV), and it does not exhibit significant cytotoxicity with multiple human cell lines in vitro (50% cytotoxic concentration, >300 μM). The compound is fully active in cervical fluids, although it exhibits decreased potency in the presence of human serum, retains its full antiviral potency for 8 h when in contact with cells, and is effective against both cell-free and cell-associated HIV. These qualities make PD 404,182 an attractive candidate anti-HIV microbicide for the prevention of HIV transmission through sexual intercourse

Development and Evaluation of an Enzyme-Linked Immunosorbent Assay for Dengue Capsid

The astonishing speed with which Dengue has spread across the world and the severity of its infection make Dengue a prime threat to human life worldwide. Unfortunately, to date there are no effective vaccines or treatments against Dengue. Since only a few assays permit rapid and sensitive detection of Dengue, we developed a specific antigen capture enzyme-linked immunosorbent assay (ELISA) for the abundant structural Dengue-2 capsid protein. We showed that the ELISA allows rapid and sensitive detection of Dengue-2 replication in various cell lines including human and mosquito cells. Using anti-capsid antibodies, we demonstrated that the capsid ELISA is as accurate as other well-characterized Dengue assays such as intracellular FACS staining (IFSA) and fluorescent focus (FFA) assays. The capsid ELISA not only represents a useful tool for in vitro basic research, but it may also represent a valuable diagnostic tool for Dengue infection in patients

Centralized versus decentralized control - A solvable stylized model in transportation

Today's supply networks consist of a certain amount of logistics objects that are enabled to interact with each other and to decide autonomously upon their next steps: in other words, they exhibit a certain degree of autonomous cooperation. Therefore, modern logistics research regards them as complex adaptive logistics systems. In order to analyze evolving dynamics and underlying implications for the respective systems' behavior as well as the potential outcomes resulting from the interaction between autonomous decision-making "smart parts", we propose in this contribution a fully solvable stylized model. We consider a population of homogeneous, autonomous interacting agents traveling on R with a given velocity that is itself corrupted by White Gaussian Noise. Based on real time observations of the positions of his neighbors, each agent is allowed to adapt his traveling velocity. These agent interactions are restricted to neighboring entities confined in finite spatial clusters (i.e. we have range-limited interactions). In the limit of a large population of neighboring agents, a mean-field dynamics can be derived and, for small interaction range, the resulting dynamics coincides with the exactly solvable Burgers' nonlinear field equation. Explicit Burgers' solution enables to explicitly appreciate the emergent structure due to the local and individual agent interactions. In particular, for strongly interactive regimes in the present model, the resulting spatial distribution of agents converges to a shock wave pattern. To compare performances of centralized versus decentralized organization, we assign cost functions incurred when velocity adaptations are triggered either by multi-agent interactions or by central control. The multi-agent cumulative costs are then compared with the costs that would be incurred by implementing an effective optimal central controller able, for a given time horizon, to reproduce an identical spatial probability distribution of agents. The resulting optimal control problem can be solved exactly and the corresponding costs can be expressed as the Kullback-Leibler relative entropy between the free and the controlled probability measures. This enables one to conclude that for time horizons shorter than a critical value, multi-agent interactions generate smaller cumulative costs than an optimal effective central controller. (C) 2010 Elsevier B.V. All rights reserved

Campylobacter Antimicrobial Drug Resistance among Humans, Broiler Chickens, and Pigs, France

We describe isolates from human Campylobacter infection in the French population and the isolates' antimicrobial drug resistance patterns since 1986 and compare the trends with those of isolates from broiler chickens and pigs from 1999 to 2004. Among 5,685 human Campylobacter isolates, 76.2% were C. jejuni, 17.2% C. coli, and 5.0% C. fetus. Resistance to nalidixic acid increased from 8.2% in 1990 to 26.3% in 2004 (p<10-3), and resistance to ampicillin was high over time. Nalidixic acid resistance was greater for C. coli (21.3%) than for C. jejuni (14.9%, p<10-3). C. jejuni resistance to ciprofloxacin in broilers decreased from 31.7% in 2002 to 9.0% in 2004 (p = 0.02). The patterns of resistance to quinolones and fluoroquinolones were similar between 1999 and 2004 in human and broiler isolates for C. jejuni. These results suggest a potential benefit of a regulation policy limiting use of antimicrobial drugs in food animals