314 research outputs found

    Soliton pair creation in classical wave scattering

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    We study classical production of soliton-antisoliton pairs from colliding wave packets in (1+1)-dimensional scalar field model. Wave packets represent multiparticle states in quantum theory; we characterize them by energy E and particle number N. Sampling stochastically over the forms of wave packets, we find the entire region in (E,N) plane which corresponds to classical creation of soliton pairs. Particle number is parametrically large within this region meaning that the probability of soliton-antisoliton pair production in few-particle collisions is exponentially suppressed.Comment: 16 pages, 8 figures, journal version; misprint correcte

    Identification of Antifungal Compounds Active against Candida albicans Using an Improved High-Throughput Caenorhabditis elegans Assay

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    Candida albicans, the most common human pathogenic fungus, can establish a persistent lethal infection in the intestine of the microscopic nematode Caenorhabditis elegans. The C. elegans–C. albicans infection model was previously adapted to screen for antifungal compounds. Modifications to this screen have been made to facilitate a high-throughput assay including co-inoculation of nematodes with C. albicans and instrumentation allowing precise dispensing of worms into assay wells, eliminating two labor-intensive steps. This high-throughput method was utilized to screen a library of 3,228 compounds represented by 1,948 bioactive compounds and 1,280 small molecules derived via diversity-oriented synthesis. Nineteen compounds were identified that conferred an increase in C. elegans survival, including most known antifungal compounds within the chemical library. In addition to seven clinically used antifungal compounds, twelve compounds were identified which are not primarily used as antifungal agents, including three immunosuppressive drugs. This assay also allowed the assessment of the relative minimal inhibitory concentration, the effective concentration in vivo, and the toxicity of the compound in a single assay

    Photodynamic and Antibiotic Therapy Impair the Pathogenesis of Enterococcus faecium in a Whole Animal Insect Model

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    Enterococcus faecium has emerged as one of the most important pathogens in healthcare-associated infections worldwide due to its intrinsic and acquired resistance to many antibiotics, including vancomycin. Antimicrobial photodynamic therapy (aPDT) is an alternative therapeutic platform that is currently under investigation for the control and treatment of infections. PDT is based on the use of photoactive dye molecules, widely known as photosensitizer (PS). PS, upon irradiation with visible light, produces reactive oxygen species that can destroy lipids and proteins causing cell death. We employed Galleria mellonella (the greater wax moth) caterpillar fatally infected with E. faecium to develop an invertebrate host model system that can be used to study the antimicrobial PDT (alone or combined with antibiotics). In the establishment of infection by E. faecium in G. mellonella, we found that the G. mellonella death rate was dependent on the number of bacterial cells injected into the insect hemocoel and all E. faecium strains tested were capable of infecting and killing G. mellonella. Antibiotic treatment with ampicillin, gentamicin or the combination of ampicillin and gentamicin prolonged caterpillar survival infected by E. faecium (P = 0.0003, P = 0.0001 and P = 0.0001, respectively). In the study of antimicrobial PDT, we verified that methylene blue (MB) injected into the insect followed by whole body illumination prolonged the caterpillar survival (P = 0.0192). Interestingly, combination therapy of larvae infected with vancomycin-resistant E. faecium, with antimicrobial PDT followed by vancomycin, significantly prolonged the survival of the caterpillars when compared to either antimicrobial PDT (P = 0.0095) or vancomycin treatment alone (P = 0.0025), suggesting that the aPDT made the vancomycin resistant E. faecium strain more susceptible to vancomycin action. In summary, G. mellonella provides an invertebrate model host to study the antimicrobial PDT and to explore combinatorial aPDT-based treatments

    The Contrasting Role of Extracellular Vesicles in Vascular Inflammation and Tissue Repair

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    Tissue engineering of functional articular cartilage: the current status

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    Osteoarthritis is a degenerative joint disease characterized by pain and disability. It involves all ages and 70% of people aged >65 have some degree of osteoarthritis. Natural cartilage repair is limited because chondrocyte density and metabolism are low and cartilage has no blood supply. The results of joint-preserving treatment protocols such as debridement, mosaicplasty, perichondrium transplantation and autologous chondrocyte implantation vary largely and the average long-term result is unsatisfactory. One reason for limited clinical success is that most treatments require new cartilage to be formed at the site of a defect. However, the mechanical conditions at such sites are unfavorable for repair of the original damaged cartilage. Therefore, it is unlikely that healthy cartilage would form at these locations. The most promising method to circumvent this problem is to engineer mechanically stable cartilage ex vivo and to implant that into the damaged tissue area. This review outlines the issues related to the composition and functionality of tissue-engineered cartilage. In particular, the focus will be on the parameters cell source, signaling molecules, scaffolds and mechanical stimulation. In addition, the current status of tissue engineering of cartilage will be discussed, with the focus on extracellular matrix content, structure and its functionality

    Drug discovery: Insights from the invertebrate Caenorhabditis elegans

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    Therapeutic drug development is a long, expensive, and complex process that usually takes 12–15 years. In the early phases of drug discovery, in particular, there is a growing need for animal models that ensure the reduction in both cost and time. Caenorhabditis elegans has been traditionally used to address fundamental aspects of key biological processes, such as apoptosis, aging, and gene expression regulation. During the last decade, with the advent of large-scale platforms for screenings, this invertebrate has also emerged as an essential tool in the pharmaceutical research industry to identify novel drugs and drug targets. In this review, we discuss the reasons why C. elegans has been positioned as an outstanding cost-effective option for drug discovery, highlighting both the advantages and drawbacks of this model. Particular attention is paid to the suitability of this nematode in large-scale genetic and pharmacological screenings. High-throughput screenings in C. elegans have indeed contributed to the breakthrough of a wide variety of candidate compounds involved in extensive fields including neurodegeneration, pathogen infections and metabolic disorders. The versatility of this nematode, which enables its instrumentation as a model of human diseases, is another attribute also herein underscored. As illustrative examples, we discuss the utility of C. elegans models of both human neurodegenerative diseases and parasitic nematodes in the drug discovery industry. Summing up, this review aims to demonstrate the impact of C. elegans models on the drug discovery pipeline.Fil: Giunti, SebastiĂĄn. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - BahĂ­a Blanca. Instituto de Investigaciones BioquĂ­micas de BahĂ­a Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂ­micas de BahĂ­a Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂ­a, BioquĂ­mica y Farmacia; ArgentinaFil: Andersen, Natalia Denise. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - BahĂ­a Blanca. Instituto de Investigaciones BioquĂ­micas de BahĂ­a Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂ­micas de BahĂ­a Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂ­a, BioquĂ­mica y Farmacia; ArgentinaFil: Rayes, Diego HernĂĄn. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - BahĂ­a Blanca. Instituto de Investigaciones BioquĂ­micas de BahĂ­a Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂ­micas de BahĂ­a Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂ­a, BioquĂ­mica y Farmacia; ArgentinaFil: de Rosa, Maria Jose. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - BahĂ­a Blanca. Instituto de Investigaciones BioquĂ­micas de BahĂ­a Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂ­micas de BahĂ­a Blanca; Argentina. Universidad Nacional del Sur. Departamento de BiologĂ­a, BioquĂ­mica y Farmacia; Argentin

    Measurement of the branching fraction for B−→D0K∗−B^- \to D^0 K^{*-}

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    We present a measurement of the branching fraction for the decay B- --> D0 K*- using a sample of approximately 86 million BBbar pairs collected by the BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the K*- through its decay to K0S pi-. We measure the branching fraction to be B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}

    Observation of a significant excess of π0π0\pi^{0}\pi^{0} events in B meson decays

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    We present an observation of the decay B0→π0π0B^{0} \to \pi^{0} \pi^{0} based on a sample of 124 million BBˉB\bar{B} pairs recorded by the BABAR detector at the PEP-II asymmetric-energy BB Factory at SLAC. We observe 46±13±346 \pm 13 \pm 3 events, where the first error is statistical and the second is systematic, corresponding to a significance of 4.2 standard deviations including systematic uncertainties. We measure the branching fraction \BR(B^{0} \to \pi^{0} \pi^{0}) = (2.1 \pm 0.6 \pm 0.3) \times 10^{-6}, averaged over B0B^{0} and Bˉ0\bar{B}^{0} decays

    Measurements of branching fractions for B^+ → p^+Îł, B^0 → p^0Îł, and B^0 → Ï‰Îł

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    We present branching fraction measurements for the radiative decays B^+ → ρ^+ Îł, B^0 → ρ^0 Îł, and B^0 → Ï‰Îł. The analysis is based on a data sample of 465 × 10^6 B[overline B] events collected with the BABAR detector at the PEP-II asymmetric-energy B Factory located at the Stanford Linear Accelerator Center. We find [script B](B^+ → ρ^+ Îł) = (1.20_(-0.37)^(+0.42) ± 0.20) × 10^(-6), [script B](B^0 → ρ^0Îł) = (0.97_(-0.22)^(+0.24) ± 0.06) × 10^(-6), and a 90% C.L. upper limit [script B](B^0 → Ï‰Îł) < 0.9 × 10^(-6), where the first error is statistical and the second is systematic. We also measure the isospin-violating quantity Γ(B^+ → ρ^+ Îł)/2Γ(B^0 → ρ^0Îł)-1 = -0.43_(-0.22)^(+0.25)±0.10

    Observation of the Decay B=> J/psi eta K and Search for X(3872)=> J/psi eta

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    We report the observation of the BB meson decay B±→J/ψηK±B^\pm\to J/\psi \eta K^\pm and evidence for the decay B0→J/ψηKS0B^0\to J/\psi \eta K^0_S, using {90} million BBbarBBbar events collected at the \ensuremath{\Upsilon{(4S)}}\xspace resonance with the BaBarBaBar detector at the PEP-II e+e−e^+ e^- asymmetric-energy storage ring. We obtain branching fractions of B\cal{B}(B±→J/ψηK±(B^\pm\to J/\psi \eta K^{\pm})=(10.8±2.3(stat.)±2.4(syst.))×10−5(10.8\pm 2.3(\rm{stat.})\pm 2.4(\rm{syst.}))\times 10^{-5} and B\cal{B}(B0→J/ψηKS0(B^0\to J/\psi\eta K_{\rm{S}}^{0})=(8.4±2.6(stat.)±2.7(syst.))×10−5(8.4\pm 2.6(\rm{stat.})\pm 2.7(\rm{syst.}))\times 10^{-5}. We search for the new narrow mass state, the X(3872), recently reported by the Belle Collaboration, in the decay B^\pm\to X(3872)K^\pm, X(3872)\to \jpsi \eta and determine an upper limit of B\cal{B}(B^\pm \to X(3872) K^\pm \to \jpsi \eta K^\pm) <7.7×10−6<7.7\times 10^{-6} at 90% C.L.Comment: 7 pages and two figures, submitted to Phys. Rev. Lett
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