522 research outputs found
Cluster-mining: An approach for determining core structures of metallic nanoparticles from atomic pair distribution function data
We present a novel approach for finding and evaluating structural models of
small metallic nanoparticles. Rather than fitting a single model with many
degrees of freedom, the approach algorithmically builds libraries of
nanoparticle clusters from multiple structural motifs, and individually fits
them to experimental PDFs. Each cluster-fit is highly constrained. The
approach, called cluster-mining, returns all candidate structure models that
are consistent with the data as measured by a goodness of fit. It is highly
automated, easy to use, and yields models that are more physically realistic
and result in better agreement to the data than models based on cubic
close-packed crystallographic cores, often reported in the literature for
metallic nanoparticles
A platform for the discovery of new macrolide antibiotics.
The chemical modification of structurally complex fermentation products, a process known as semisynthesis, has been an important tool in the discovery and manufacture of antibiotics for the treatment of various infectious diseases. However, many of the therapeutics obtained in this way are no longer effective, because bacterial resistance to these compounds has developed. Here we present a practical, fully synthetic route to macrolide antibiotics by the convergent assembly of simple chemical building blocks, enabling the synthesis of diverse structures not accessible by traditional semisynthetic approaches. More than 300 new macrolide antibiotic candidates, as well as the clinical candidate solithromycin, have been synthesized using our convergent approach. Evaluation of these compounds against a panel of pathogenic bacteria revealed that the majority of these structures had antibiotic activity, some efficacious against strains resistant to macrolides in current use. The chemistry we describe here provides a platform for the discovery of new macrolide antibiotics and may also serve as the basis for their manufacture
Bounded Expectations: Resource Analysis for Probabilistic Programs
This paper presents a new static analysis for deriving upper bounds on the
expected resource consumption of probabilistic programs. The analysis is fully
automatic and derives symbolic bounds that are multivariate polynomials of the
inputs. The new technique combines manual state-of-the-art reasoning techniques
for probabilistic programs with an effective method for automatic
resource-bound analysis of deterministic programs. It can be seen as both, an
extension of automatic amortized resource analysis (AARA) to probabilistic
programs and an automation of manual reasoning for probabilistic programs that
is based on weakest preconditions. As a result, bound inference can be reduced
to off-the-shelf LP solving in many cases and automatically-derived bounds can
be interactively extended with standard program logics if the automation fails.
Building on existing work, the soundness of the analysis is proved with respect
to an operational semantics that is based on Markov decision processes. The
effectiveness of the technique is demonstrated with a prototype implementation
that is used to automatically analyze 39 challenging probabilistic programs and
randomized algorithms. Experimental results indicate that the derived constant
factors in the bounds are very precise and even optimal for many programs
Phase space reduction of the one-dimensional Fokker-Planck (Kramers) equation
A pointlike particle of finite mass m, moving in a one-dimensional viscous
environment and biased by a spatially dependent force, is considered. We
present a rigorous mapping of the Fokker-Planck equation, which determines
evolution of the particle density in phase space, onto the spatial coordinate
x. The result is the Smoluchowski equation, valid in the overdamped limit,
m->0, with a series of corrections expanded in powers of m. They are determined
unambiguously within the recurrence mapping procedure. The method and the
results are interpreted on the simplest model with no field and on the damped
harmonic oscillator.Comment: 13 pages, 1 figur
Human Galectins Induce Conversion of Dermal Fibroblasts into Myofibroblasts and Production of Extracellular Matrix: Potential Application in Tissue Engineering and Wound Repair
Members of the galectin family of endogenous lectins are potent adhesion/growth-regulatory effectors. Their multi-functionality opens possibilities for their use in bioapplications. We studied whether human galectins induce the conversion of human dermal fibroblasts into myofibroblasts (MFBs) and the production of a bioactive extracellular matrix scaffold is suitable for cell culture. Testing a panel of galectins of all three subgroups, including natural and engineered variants, we detected activity for the proto-type galectin-1 and galectin-7, the chimera-type galectin-3 and the tandem-repeat-type galectin-4. The activity of galectin-1 required the integrity of the carbohydrate recognition domain. It was independent of the presence of TGF-beta 1, but it yielded an additive effect. The resulting MFBs, relevant, for example, for tumor progression, generated a matrix scaffold rich in fibronectin and galectin-1 that supported keratinocyte culture without feeder cells. Of note, keratinocytes cultured on this substratum presented a stem-like cell phenotype with small size and keratin-19 expression. In vivo in rats, galectin-1 had a positive effect on skin wound closure 21 days after surgery. In conclusion, we describe the differential potential of certain human galectins to induce the conversion of dermal fibroblasts into MFBs and the generation of a bioactive cell culture substratum. Copyright (C) 2011 S. Karger AG, Base
Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae. II: The Second Year (2009-2010)
As an extension of the project in Kato et al. (2009, arXiv:0905.1757), we
collected times of superhump maxima for 61 SU UMa-type dwarf novae mainly
observed during the 2009-2010 season. The newly obtained data confirmed the
basic findings reported in Kato et al. (2009): the presence of stages A-C, as
well as the predominance of positive period derivatives during stage B in
systems with superhump periods shorter than 0.07 d. There was a systematic
difference in period derivatives for systems with superhump periods longer than
0.075 d between this study and Kato et al. (2009). We suggest that this
difference is possibly caused by the relative lack of frequently outbursting SU
UMa-type dwarf novae in this period regime in the present study. We recorded a
strong beat phenomenon during the 2009 superoutburst of IY UMa. The close
correlation between the beat period and superhump period suggests that the
changing angular velocity of the apsidal motion of the elliptical disk is
responsible for the variation of superhump periods. We also described three new
WZ Sge-type objects with established early superhumps and one with likely early
superhumps. We also suggest that two systems, VX For and EL UMa, are WZ
Sge-type dwarf novae with multiple rebrightenings. The O-C variation in OT
J213806.6+261957 suggests that the frequent absence of rebrightenings in very
short-Porb objects can be a result of sustained superoutburst plateau at the
epoch when usual SU UMa-type dwarf novae return to quiescence preceding a
rebrightening. We also present a formulation for a variety of Bayesian
extension to traditional period analyses.Comment: 63 pages, 77 figures, 1 appendix, Accepted for publication in PASJ,
data correctio
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Evaluation in Mice of a Conjugate Vaccine for Cholera Made from Vibrio cholerae O1 (Ogawa) O-Specific Polysaccharide
Background: Protective immunity against cholera is serogroup specific. Serogroup specificity in Vibrio cholerae is determined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). Generally, polysaccharides are poorly immunogenic, especially in young children. Methodology Here we report the evaluation in mice of a conjugate vaccine for cholera (OSP:TThc) made from V. cholerae O1 Ogawa O-Specific Polysaccharide–core (OSP) and recombinant tetanus toxoid heavy chain fragment (TThc). We immunized mice intramuscularly on days 0, 21, and 42 with OSP:TThc or OSP only, with or without dmLT, a non-toxigenic immunoadjuvant derived from heat labile toxin of Escherichia coli. Principal Findings We detected significant serum IgG antibody responses targeting OSP following a single immunization in mice receiving OSP:TThc with or without adjuvant. Anti-LPS IgG responses were detected following a second immunization in these cohorts. No anti-OSP or anti-LPS IgG responses were detected at any time in animals receiving un-conjugated OSP with or without immunoadjuvant, and in animals receiving immunoadjuvant alone. Responses were highest following immunization with adjuvant. Serum anti-OSP IgM responses were detected in mice receiving OSP:TThc with or without immunoadjuvant, and in mice receiving unconjugated OSP. Serum anti-LPS IgM and vibriocidal responses were detected in all vaccine cohorts except in mice receiving immunoadjuvant alone. No significant IgA anti-OSP or anti-LPS responses developed in any group. Administration of OSP:TThc and adjuvant also induced memory B cell responses targeting OSP and resulted in 95% protective efficacy in a mouse lethality cholera challenge model. Conclusion: We describe a protectively immunogenic cholera conjugate in mice. Development of a cholera conjugate vaccine could assist in inducing long-term protective immunity, especially in young children who respond poorly to polysaccharide antigens
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