Analysis of scale energy budgets in wall turbulence using dual plane PIV

The scale energy budget in the near wall region is a subject of great interest in turbulent flows since it combines concepts from independent analysis in physical space and scale space. Earlier, this energy budget was studied numerically using Direct Numerical Simulation (DNS) data and experimentally using low resolution dual plane Particle Image Velocimetry (PIV) data. It was observed that the low resolution PIV data were not sufficient to accurately capture the dynamics of the energy balance and hence high resolution experiments were conducted in similar experimental conditions. The results from these high resolution data conducted in two locations of the logarithmic layer of the boundary layer indicate that the resolution of these experiments is sufficient to capture the scale energy budget in the near wall region. Predictions of the cross-over scale, which is related to the relative importance of production and transfer of turbulent kinetic energy, are found to match expected trends, and illustrate that the experimental technique provides a powerful tool for the scale energy budget analysis

BAY61-3606 Affects the Viability of Colon Cancer Cells in a Genotype-Directed Manner

Background: K-RAS mutation poses a particularly difficult problem for cancer therapy. Activating mutations in K-RAS are common in cancers of the lung, pancreas, and colon and are associated with poor response to therapy. As such, targeted therapies that abrogate K-RAS-induced oncogenicity would be of tremendous value. Methods: We searched for small molecule kinase inhibitors that preferentially affect the growth of colorectal cancer cells expressing mutant K-RAS. The mechanism of action of one inhibitor was explored using chemical and genetic approaches. Results: We identified BAY61-3606 as an inhibitor of proliferation in colorectal cancer cells expressing mutant forms of K-RAS, but not in isogenic cells expressing wild-type K-RAS. In addition to its anti-proliferative effects in mutant cells, BAY61-3606 exhibited a distinct biological property in wild-type cells in that it conferred sensitivity to inhibition of RAF. In this context, BAY61-3606 acted by inhibiting MAP4K2 (GCK), which normally activates NFκβ signaling in wild-type cells in response to inhibition of RAF. As a result of MAP4K2 inhibition, wild-type cells became sensitive to AZ-628, a RAF inhibitor, when also treated with BAY61-3606. Conclusions: These studies indicate that BAY61-3606 exerts distinct biological activities in different genetic contexts

5‑Amidodansyl‑U (U^D) Peptide Nucleic Acid (PNA) as a Fluorescent Sensor of the Local Dielectric Constant (ε) in PNA Duplexes: Major Grooves in PNA Duplexes Are More Hydrophobic Than Major Grooves in DNA–DNA Duplexes

Peptide nucleic acids (PNA) show great promise for the development of antisense drugs owing to their superior binding property with complementary DNA/RNA. They recognize complementary DNA/RNA/PNA via hydrogen bonding and electrostatic interaction whose strengths depend on their chemical environment. It is therefore important to understand the effects of local dielectrics in the major/minor grooves of PNA:DNA/RNA/PNA duplexes that influence its superior binding. By employing 5-amidodansyl U on PNA as a fluoroprobe of the local environment and measuring the polarity-sensitive Stokes shift, it is demonstrated that compared to the major groove of DNA–DNA duplexes, the analogous major groove of PNA:DNA/RNA/PNA duplexes is more hydrophobic (lower ε), and sequence-dependent polarity changes are seen in all PNA duplexes. The results highlight the effects of chemical modifications of backbone and base sequence in nucleic acids on the local environment of grooves, leading to a dielectric continuum that may have implications for the binding of ligands and macromolecules in grooves of nucleic acid duplexes

Reynolds number effects on scale energy balance in wall turbulence

The scale energy budget utilizes a modified version of the classical Kolmogorov equation of wall turbulence to develop an evolution equation for the second order structure function [R. J. Hill, \u201cExact second-order structure-function relationships,\u201d J. Fluid Mech. 468, 317 (2002)]. This methodology allows for the simultaneous characterization of the energy cascade and spatial fluxes in turbulent shear flows across the entire physical domain as well as the range of scales. The present study utilizes this methodology to characterize the effects of Reynolds number on the balance of energy fluxes in turbulent channel flows. Direct numerical simulation data in the range Re_tau = 300\u2013934 are compared to previously published results at Re_tau =180

Structure of Mycobacterium tuberculosis Singlestranded DNA-binding Protein. Variability in Quaternary Structure and Its Implications

Single-stranded DNA-binding protein (SSB) is an essential protein necessary for the functioning of the DNA replication, repair and recombination machineries. Here we report the structure of the DNA-binding domain of Mycobacterium tuberculosis SSB (MtuSSB) in four different crystals distributed in two forms. The structure of one of the forms was solved by a combination of isomorphous replacement and anomalous scattering. This structure was used to determine the structure of the other form by molecular replacement. The polypeptide chain in the structure exhibits the oligonucleotide binding fold. The globular core of the molecule in different subunits in the two forms and those in Escherichia coli SSB (EcoSSB) and human mitochondrial SSB (HMtSSB) have similar structure, although the three loops exhibit considerable structural variation. However, the tetrameric MtuSSB has an as yet unobserved quaternary association. This quaternary structure with a unique dimeric interface lends the oligomeric protein greater stability, which may be of significance to the functioning of the protein under conditions of stress. Also, as a result of the variation in the quaternary structure the path adopted by the DNA to wrap around MtuSSB is expected to be different from that of EcoSSB

The crystal structure of the single-stranded DNA-binding protein from Mycobacterium tuberculosis

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Structure of Mycobacterium tuberculosis single-stranded DNA-binding protein. Variability in quaternary structure and its implications

Single-stranded DNA-binding protein (SSB) is an essential protein necessary for the functioning of the DNA replication, repair and recombination machineries. Here we report the structure of the DNA-binding domain of Mycobacterium tuberculosis SSB (MtuSSB) in four different crystals distributed in two forms. The structure of one of the forms was solved by a combination of isomorphous replacement and anomalous scattering. This structure was used to determine the structure of the other form by molecular replacement. The polypeptide chain in the structure exhibits the oligonucleotide binding fold. The globular core of the molecule in different subunits in the two forms and those in Escherichia coli SSB (EcoSSB) and human mitochondrial SSB (HMtSSB) have similar structure, although the three loops exhibit considerable structural variation. However, the tetrameric MtuSSB has an as yet unobserved quaternary association. This quaternary structure with a unique dimeric interface lends the oligomeric protein greater stability, which may be of significance to the functioning of the protein under conditions of stress. Also, as a result of the variation in the quaternary structure the path adopted by the DNA to wrap around MtuSSB is expected to be different from that of EcoSSB