174 research outputs found
Goertler instability on an airfoil
An effective computational scheme was developed to study the growth/damping of Goertler vortices along walls of variable curvature. Computational experiments indicate that when the amplification rates for the u-, v-, and w-perturbations are the same, the finite difference approach to solve the initial value problem and the normal mode approach give identical results for the Blasius boundary layer on constant curvature concave walls. The growth of Goertler vortices was rapid in the concave regions and was followed by sharp damping in the convex region. However, multiple sets of counter-rotating vortices were formed and remained far downstream in the convex region. The current computational scheme can be easily extended to more realistic problems including variable pressure gradients and suction effects
Frequency dependent core shifts and parameter estimation for the blazar 3C 454.3
We study the core shift effect in the parsec scale jet of the blazar 3C 454.3
using the 4.8 GHz - 36.8 GHz radio light curves obtained from three decades of
continuous monitoring. From a piecewise Gaussian fit to each flare, time lags
between the observation frequencies and spectral indices
based on peak amplitudes are determined. From the fit , indicating equipartition between
the magnetic field energy density and the particle energy density. From the fit
, is in the range to . A mean
magnetic field strength at 1 pc, G, and at the core,
mG, are inferred, consistent with previous
estimates. The measure of core position offset is
pc GHz when averaged over all frequency pairs. Based on the
statistical trend shown by the measured core radius as a
function of , we infer that the synchrotron opacity model may not be valid
for all cases. A Fourier periodogram analysis yields power law slopes in the
range to describing the power spectral density shape and gives
bend timescales in the range yr. This result, and both positive
and negative , indicate that the flares originate from multiple shocks
in a small region. Important objectives met in our study include: the
demonstration of the computational efficiency and statistical basis of the
piecewise Gaussian fit; consistency with previously reported results; evidence
for the core shift dependence on observation frequency and its utility in jet
diagnostics in the region close to the resolving limit of very long baseline
interferometry observations.Comment: 12 pages, 11 figures (23 sub-figures), 5 tables. Accepted for
publication in MNRA
A peculiar multi-wavelength flare in the Blazar 3C 454.3
The blazar 3C454.3 exhibited a strong flare seen in gamma-rays, X-rays, and
optical/NIR bands during 3--12 December 2009. Emission in the V and J bands
rose more gradually than did the gamma-rays and soft X-rays, though all peaked
at nearly the same time. Optical polarization measurements showed dramatic
changes during the flare, with a strong anti-correlation between optical flux
and degree of polarization (which rose from ~ 3% to ~ 20%) during the declining
phase of the flare. The flare was accompanied by large rapid swings in
polarization angle of ~ 170 degree. This combination of behaviors appear to be
unique. We have cm-band radio data during the same period but they show no
correlation with variations at higher frequencies. Such peculiar behavior may
be explained using jet models incorporating fully relativistic effects with a
dominant source region moving along a helical path or by a shock-in-jet model
incorporating three-dimensional radiation transfer if there is a dominant
helical magnetic field. We find that spectral energy distributions at different
times during the flare can be fit using modified one-zone models where only the
magnetic field strength and particle break frequencies and normalizations need
change. An optical spectrum taken at nearly the same time provides an estimate
for the central black hole mass of ~ 2.3 * 10^9 M_sun. We also consider two
weaker flares seen during the d span over which multi-band data are
available. In one of them, the V and J bands appear to lead the -ray
and X-ray bands by a few days; in the other, all variations are simultaneous.Comment: 11 pages, 4 figures, 2 tables; MNRAS in pres
Multiwavelength Intraday Variability of the BL Lac S5 0716+714
We report results from a 1 week multi-wavelength campaign to monitor the BL
Lac object S5 0716+714 (on December 9-16, 2009). In the radio bands the source
shows rapid (~ (0.5-1.5) day) intra-day variability with peak amplitudes of up
to ~ 10 %. The variability at 2.8 cm leads by about 1 day the variability at 6
cm and 11 cm. This time lag and more rapid variations suggests an intrinsic
contribution to the source's intraday variability at 2.8 cm, while at 6 cm and
11 cm interstellar scintillation (ISS) seems to predominate. Large and
quasi-sinusoidal variations of ~ 0.8 mag were detected in the V, R and I-bands.
The X-ray data (0.2-10 keV) do not reveal significant variability on a 4 day
time scale, favoring reprocessed inverse-Compton over synchrotron radiation in
this band. The characteristic variability time scales in radio and optical
bands are similar. A quasi-periodic variation (QPO) of 0.9 - 1.1 days in the
optical data may be present, but if so it is marginal and limited to 2.2
cycles. Cross-correlations between radio and optical are discussed. The lack of
a strong radio-optical correlation indicates different physical causes of
variability (ISS at long radio wavelengths, source intrinsic origin in the
optical), and is consistent with a high jet opacity and a compact synchrotron
component peaking at ~= 100 GHz in an ongoing very prominent flux density
outburst. For the campaign period, we construct a quasi-simultaneous spectral
energy distribution (SED), including gamma-ray data from the FERMI satellite.
We obtain lower limits for the relativistic Doppler-boosting of delta >= 12-26,
which for a BL\,Lac type object, is remarkably high.Comment: 16 pages, 15 figures, table 2; Accepted for Publication in MNRA
A comparison of common programming languages used in bioinformatics
<p>Abstract</p> <p>Background</p> <p>The performance of different programming languages has previously been benchmarked using abstract mathematical algorithms, but not using standard bioinformatics algorithms. We compared the memory usage and speed of execution for three standard bioinformatics methods, implemented in programs using one of six different programming languages. Programs for the Sellers algorithm, the Neighbor-Joining tree construction algorithm and an algorithm for parsing BLAST file outputs were implemented in C, C++, C#, Java, Perl and Python.</p> <p>Results</p> <p>Implementations in C and C++ were fastest and used the least memory. Programs in these languages generally contained more lines of code. Java and C# appeared to be a compromise between the flexibility of Perl and Python and the fast performance of C and C++. The relative performance of the tested languages did not change from Windows to Linux and no clear evidence of a faster operating system was found.</p> <p>Source code and additional information are available from <url>http://www.bioinformatics.org/benchmark/</url></p> <p>Conclusion</p> <p>This benchmark provides a comparison of six commonly used programming languages under two different operating systems. The overall comparison shows that a developer should choose an appropriate language carefully, taking into account the performance expected and the library availability for each language.</p
DQB1*0602 rather than DRB1*1501 confers susceptibility to multiple sclerosis-like disease induced by proteolipid protein (PLP)
<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is associated with pathogenic autoimmunity primarily focused on major CNS-myelin target antigens including myelin basic protein (MBP), proteolipidprotein (PLP), myelin oligodendrocyte protein (MOG). MS is a complex trait whereby the HLA genes, particularly class-II genes of HLA-DR15 haplotype, dominate the genetic contribution to disease-risk. Due to strong linkage disequilibrium in HLA-II region, it has been hard to establish precisely whether the functionally relevant effect derives from the DRB1*1501, DQA1*0102-DQB1*0602, or DRB5*0101 loci of HLA-DR15 haplotype, their combinations, or their epistatic interactions. Nevertheless, most genetic studies have indicated DRB1*1501 as a primary risk factor in MS. Here, we used 'HLA-humanized' mice to discern the potential relative contribution of DRB1*1501 and DQB1*0602 alleles to susceptibility to "humanized" MS-like disease induced by PLP, one of the most prominent and encephalitogenic target-antigens implicated in human MS.</p> <p>Methods</p> <p>The HLA-DRB1*1501- and HLA-DQB1*0602-Tg mice (MHC-II<sup>-/-</sup>), and control non-HLA-DR15-relevant-Tg mice were immunized with a set of overlapping PLP peptides or with recombinant soluble PLP for induction of "humanized" MS-like disease, as well as for ex-vivo analysis of immunogenic/immunodominant HLA-restricted T-cell epitopes and associated cytokine secretion profile.</p> <p>Results</p> <p>PLP autoimmunity in both HLA-DR15-Tg mice was focused on 139-151 and 175-194 epitopes. Strikingly, however, the HLA-DRB1*1501-transgenics were refractory to disease induction by any of the overlapping PLP peptides, while HLA-DQB1*0602 transgenics were susceptible to disease induction by PLP139-151 and PLP175-194 peptides. Although both transgenics responded to both peptides, the PLP139-151- and PLP175-194-reactive T-cells were directed to Th1/Th17 phenotype in DQB1*0602-Tg mice and towards Th2 in DRB1*1501-Tg mice.</p> <p>Conclusions</p> <p>While genome studies map a strong MS susceptibility effect to the region of DRB1*1501, our findings offer a rationale for potential involvement of pathogenic DQ6-associated autoimmunity in MS. Moreover, that DQB1*0602, but not DRB1*1501, determines disease-susceptibility to PLP in HLA-transgenics, suggests a potential differential, functional role for DQB1*0602 as a predisposing allele in MS. This, together with previously demonstrated disease-susceptibility to MBP and MOG in DRB1*1501-transgenics, also suggests a differential role for DRB1*1501 and DQB1*0602 depending on target antigen and imply a potential complex 'genotype/target antigen/phenotype' relationship in MS heterogeneity.</p
inGeno – an integrated genome and ortholog viewer for improved genome to genome comparisons
BACKGROUND: Systematic genome comparisons are an important tool to reveal gene functions, pathogenic features, metabolic pathways and genome evolution in the era of post-genomics. Furthermore, such comparisons provide important clues for vaccines and drug development. Existing genome comparison software often lacks accurate information on orthologs, the function of similar genes identified and genome-wide reports and lists on specific functions. All these features and further analyses are provided here in the context of a modular software tool "inGeno" written in Java with Biojava subroutines. RESULTS: InGeno provides a user-friendly interactive visualization platform for sequence comparisons (comprehensive reciprocal protein – protein comparisons) between complete genome sequences and all associated annotations and features. The comparison data can be acquired from several different sequence analysis programs in flexible formats. Automatic dot-plot analysis includes output reduction, filtering, ortholog testing and linear regression, followed by smart clustering (local collinear blocks; LCBs) to reveal similar genome regions. Further, the system provides genome alignment and visualization editor, collinear relationships and strain-specific islands. Specific annotations and functions are parsed, recognized, clustered, logically concatenated and visualized and summarized in reports. CONCLUSION: As shown in this study, inGeno can be applied to study and compare in particular prokaryotic genomes against each other (gram positive and negative as well as close and more distantly related species) and has been proven to be sensitive and accurate. This modular software is user-friendly and easily accommodates new routines to meet specific user-defined requirements
Optical variability of PKS 0736+017
We present BVR photometric observations of the blazar PKS 0736+017. These
observations were carried out with three telescopes in Mexico and two in Spain
between December 1998 and April 2003. PKS 0736+017 shows remarkable variation
at different timescales and amplitudes. Maximum brightness was detected on
December 19, 2001 (B=14.90+/-0.01, V=14.34+/-0.01, and R=13.79+/-0.01). A
peculiar tendency to redden with increased brightness was detected throughout
our observations. Moreover, in one season a good correlation between flux level
and spectral slope is shown. This "anomalous" behaviour cannot be described by
common flare models of blazars. The flux vs. spectral slope correlation
observed in this and other blazars is worth further study.Comment: 8 pages, 6 figures, accepted for publication in Astronomy &
Astrophysic
Reconstitution of huPBL-NSG Mice with Donor-Matched Dendritic Cells Enables Antigen-Specific T-cell Activation
Humanized mouse models provide a unique opportunity to study human immune cells in vivo, but traditional models have been limited to the evaluation of non-specific T-cell interactions due to the absence of antigen-presenting cells. In this study, immunodeficient NOD/SCID/IL2r-γnull (NSG) mice were engrafted with human peripheral blood lymphocytes alone or in combination with donor-matched monocyte-derived dendritic cells (DC) to determine whether antigen-specific T-cell activation could be reconstituted. Over a period of 3 weeks, transferred peripheral blood lymphocytes reconstituted the spleen and peripheral blood of recipient mice with predominantly human CD45-positive lymphocytes. Animals exhibited a relatively normal CD4/CD8 ratio (average 1.63:1) as well as reconstitution of CD3/CD56 (averaging 17.8%) and CD20 subsets (averaging 4.0%). Animals reconstituted with donor-matched CD11c+ DC also demonstrated a CD11c+ population within their spleen, representing 0.27% to 0.43% of the recovered human cells with concurrent expression of HLA-DR, CD40, and CD86. When immunized with adenovirus, either as free replication-incompetent vector (AdV) or as vector-transduced DC (DC/AdV), there was activation and expansion of AdV-specific T-cells, an increase in Th1 cytokines in serum, and skewing of T-cells toward an effector/memory phenotype. T-cells recovered from animals challenged with AdV in vivo proliferated and secreted a Th1-profile of cytokines in response to DC/AdV challenge in vitro. Our results suggest that engrafting NSG mice with a combination of lymphocytes and donor-matched DC can reconstitute antigen responsiveness and allow the in vivo assessment of human immune response to viruses, vaccines, and other immune challenges
Selective and brain-penetrant ACSS2 inhibitors target breast cancer brain metastatic cells
Breast cancer brain metastasis (BCBM) typically results in an end-stage diagnosis and is hindered by a lack of brain-penetrant drugs. Tumors in the brain rely on the conversion of acetate to acetyl-CoA by the enzyme acetyl-CoA synthetase 2 (ACSS2), a key regulator of fatty acid synthesis and protein acetylation. Here, we used a computational pipeline to identify novel brain-penetrant ACSS2 inhibitors combining pharmacophore-based shape screen methodology with absorption, distribution, metabolism, and excretion (ADME) property predictions. We identified compounds AD-5584 and AD-8007 that were validated for specific binding affinity to ACSS2. Treatment of BCBM cells with AD-5584 and AD-8007 leads to a significant reduction in colony formation, lipid storage, acetyl-CoA levels and cell survival in vitro. In an ex vivo brain-tumor slice model, treatment with AD-8007 and AD-5584 reduced pre-formed tumors and synergized with irradiation in blocking BCBM tumor growth. Treatment with AD-8007 reduced tumor burden and extended survival in vivo. This study identifies selective brain-penetrant ACSS2 inhibitors with efficacy towards breast cancer brain metastasis
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