121 research outputs found
Intermittent Features of the QSO Ly Transmitted Flux: Results from Hydrodynamic Cosmological Simulations
It has been recently found that the local fluctuations of the QSO's
Ly absorption spectrum transmitted flux show spiky structures. This
implies that the mass fields of the intergalactic medium (IGM) is intermittent.
This feature cannot be explained by the clustering evolution of cosmic mass
field in the linear regimes and is also difficult to incorporate into the
hierarchical clustering scenario. We calculate the structure functions and
intermittent exponent of the IGM and HI for full hydrodynamical simulation
samples. The result shows the intermittent features of the Ly
transmitted flux fluctuations as well as the mass field of the IGM. We find
that within the error bars of current data, all the intermittent behavior of
the simulation samples are consistent with the observation. This result is
different from our earlier result (Pando et al 2002), which shows that the
intermittent behavior of samples generated by pseudo-hydro simulation cannot be
fitted with observed data. One difference between the pseudo-hydro and full
hydro simulations is in treating the dynamical relation between the IGM (or HI)
and dark matter fields. The former assumes that the IGM density distribution
traces the underlying dark matter point-by-point on scales larger than the
Jeans length in either the linear or nonlinear regimes. However, hydrodynamic
studies have found that a statistical discrepancy between the IGM field and
underlying dark matter in nonlinear regime is possible. We find that the
point-by-point correlation between the IGM density perturbations and dark
matter become weaker on comoving scales less than 2 h Mpc (in LCDM
model), which is larger than the IGM Jeans length.Comment: AAS Latex file, 38 pages,17 figures included, accepted for
publication in Ap
Efficient Mixing at low Reynolds numbers using polymer additives
Mixing in fluids is a rapidly developing field of fluid mechanics
\cite{Sreen,Shr,War}, being an important industrial and environmental problem.
The mixing of liquids at low Reynolds numbers is usually quite weak in simple
flows, and it requires special devices to be efficient. Recently, the problem
of mixing was solved analytically for a simple case of random flow, known as
the Batchelor regime \cite{Bat,Kraich,Fal,Sig,Fouxon}. Here we demonstrate
experimentally that very viscous liquids at low Reynolds number, . Here we
show that very viscous liquids containing a small amount of high molecular
weight polymers can be mixed quite efficiently at very low Reynolds numbers,
for a simple flow in a curved channel. A polymer concentration of only 0.001%
suffices. The presence of the polymers leads to an elastic instability
\cite{LMS} and to irregular flow \cite{Ours}, with velocity spectra
corresponding to the Batchelor regime \cite{Bat,Kraich,Fal,Sig,Fouxon}. Our
detailed observations of the mixing in this regime enable us to confirm sevearl
important theoretical predictions: the probability distributions of the
concentration exhibit exponential tails \cite{Fal,Fouxon}, moments of the
distribution decay exponentially along the flow \cite{Fouxon}, and the spatial
correlation function of concentration decays logarithmically.Comment: 11 pages, 5 figure
Fluid Particle Accelerations in Fully Developed Turbulence
The motion of fluid particles as they are pushed along erratic trajectories
by fluctuating pressure gradients is fundamental to transport and mixing in
turbulence. It is essential in cloud formation and atmospheric transport,
processes in stirred chemical reactors and combustion systems, and in the
industrial production of nanoparticles. The perspective of particle
trajectories has been used successfully to describe mixing and transport in
turbulence, but issues of fundamental importance remain unresolved. One such
issue is the Heisenberg-Yaglom prediction of fluid particle accelerations,
based on the 1941 scaling theory of Kolmogorov (K41). Here we report
acceleration measurements using a detector adapted from high-energy physics to
track particles in a laboratory water flow at Reynolds numbers up to 63,000. We
find that universal K41 scaling of the acceleration variance is attained at
high Reynolds numbers. Our data show strong intermittency---particles are
observed with accelerations of up to 1,500 times the acceleration of gravity
(40 times the root mean square value). Finally, we find that accelerations
manifest the anisotropy of the large scale flow at all Reynolds numbers
studied.Comment: 7 pages, 4 figure
Development of Second-Generation VEGFR Tyrosine Kinase Inhibitors: Current Status
The vascular endothelial growth factor (VEGF) signaling pathway appears to be the dominant pathway involved in tumor angiogenesis, providing a rationale for targeting the VEGF receptors (VEGFR-1, -2, and -3) in the treatment of cancers. In particular, VEGF signaling is thought to be important in renal cell carcinoma (RCC) because of the deregulation of the pathway through nearly uniform loss of the von Hippel Lindau protein. The tyrosine kinase inhibitors (TKIs) sorafenib, sunitinib, and pazopanib are approved by the US Food and Drug Administration for the treatment of advanced RCC; however, these multitargeted agents inhibit a wide range of kinase targets in addition to the VEGFRs, resulting in a range of adverse effects unrelated to efficient VEGF blockade. This article reviews recent advances in the development of the second-generation VEGFR TKIs, including the more selective VEGFR TKIs tivozanib and axitinib, and focuses on the potential benefits of novel inhibitors with improved potency and selectivity
Tumor Volume Estimation and Quasi- Continuous Administration for Most Effective Bevacizumab Therapy
Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol.We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis.In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model.Our results provide a theoretical background for a much more effective bevacizumab treatment using optimized administration
Levels of circulating CD45dimCD34+VEGFR2+ progenitor cells correlate with outcome in metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors
A Fundamental Regulatory Mechanism Operating through OmpR and DNA Topology Controls Expression of Salmonella Pathogenicity Islands SPI-1 and SPI-2
DNA topology has fundamental control over the ability of transcription factors to access their target DNA sites at gene promoters. However, the influence of DNA topology on protein–DNA and protein–protein interactions is poorly understood. For example, relaxation of DNA supercoiling strongly induces the well-studied pathogenicity gene ssrA (also called spiR) in Salmonella enterica, but neither the mechanism nor the proteins involved are known. We have found that relaxation of DNA supercoiling induces expression of the Salmonella pathogenicity island (SPI)-2 regulator ssrA as well as the SPI-1 regulator hilC through a mechanism that requires the two-component regulator OmpR-EnvZ. Additionally, the ompR promoter is autoregulated in the same fashion. Conversely, the SPI-1 regulator hilD is induced by DNA relaxation but is repressed by OmpR. Relaxation of DNA supercoiling caused an increase in OmpR binding to DNA and a concomitant decrease in binding by the nucleoid-associated protein FIS. The reciprocal occupancy of DNA by OmpR and FIS was not due to antagonism between these transcription factors, but was instead a more intrinsic response to altered DNA topology. Surprisingly, DNA relaxation had no detectable effect on the binding of the global repressor H-NS. These results reveal the underlying molecular mechanism that primes SPI genes for rapid induction at the onset of host invasion. Additionally, our results reveal novel features of the archetypal two-component regulator OmpR. OmpR binding to relaxed DNA appears to generate a locally supercoiled state, which may assist promoter activation by relocating supercoiling stress-induced destabilization of DNA strands. Much has been made of the mechanisms that have evolved to regulate horizontally-acquired genes such as SPIs, but parallels among the ssrA, hilC, and ompR promoters illustrate that a fundamental form of regulation based on DNA topology coordinates the expression of these genes regardless of their origins
Biomarkers of angiogenesis and their role in the development of VEGF inhibitors
Vascular endothelial growth factor (VEGF) has been confirmed as an important therapeutic target in randomised clinical trials in multiple disease settings. However, the extent to which individual patients benefit from VEGF inhibitors is unclear. If we are to optimise the use of these drugs or develop combination regimens that build on this efficacy, it is critical to identify those patients who are likely to benefit, particularly as these agents can be toxic and are expensive. To this end, biomarkers have been evaluated in tissue, in circulation and by imaging. Consistent drug-induced increases in plasma VEGF-A and blood pressure, as well as reductions in soluble VEGF-R2 and dynamic contrast-enhanced MRI parameters have been reported. In some clinical trials, biomarker changes were statistically significant and associated with clinical end points, but there is considerable heterogeneity between studies that are to some extent attributable to methodological issues. On the basis of observations with these biomarkers, it is now appropriate to conduct detailed prospective studies to define a suite of predictive, pharmacodynamic and surrogate response biomarkers that identify those patients most likely to benefit from and monitor their response to this novel class of drugs
Antiangiogenic drugs in ovarian cancer
Ovarian cancer continues to be a major cause of morbidity and mortality in women. Antiangiogenic treatments have emerged as a promising strategy to treat ovarian cancer. This article reviews the rationale supporting the use of antiangiogenic treatments in ovarian cancer, the clinical development of this group of drugs and the toxicities specific to this modality of treatment
Blood vessels as targets in tumor therapy
The landmark papers published by Judah Folkman in the early 1970s on tumor angiogenesis and therapeutic implications promoted the rapid development of a very dynamic field where basic scientists, oncologists, and pharmaceutical industry joined forces to determine the molecular mechanisms in blood vessel formation and find means to exploit this knowledge in suppressing tumor vascularization and growth. A wealth of information has been collected on angiogenic growth factors, and in 2004 the first specific blood vessel-targeted cancer therapy was introduced: a neutralizing antibody against vascular endothelial growth factor (VEGF). Now (2011) we know that suppression of tumor angiogenesis may be a double-edged sword and that the therapy needs to be further refined and individualized. This review describes the hallmarks of tumor vessels, how different angiogenic growth factors exert their function, and the perspectives for future development of anti-angiogenic therapy
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