Velocity Fluctuations in Helical Propulsion: How Small Can a Propeller Be

Helical propulsion is at the heart of locomotion strategies utilized by various natural and artificial swimmers. We used experimental observations and a numerical model to study the various fluctuation mechanisms that determine the performance of an externally driven helical propeller as the size of the helix is reduced. From causality analysis, an overwhelming effect of orientational noise at low length scales is observed, which strongly affects the average velocity and direction of motion of a propeller. For length scales smaller than a few micrometers in aqueous media, the operational frequency for the propulsion system would have to increase as the inverse cube of the size, which can be the limiting factor for a helical propeller to achieve locomotion in the desired direction.

Co-evolution of specific amino acid in sigma 1.2 region and nucleotide base in the discriminator to act as sensors of small molecule effectors of transcription initiation in mycobacteria

The transcription from rrn and a number of other promoters is regulated by initiating ribonucleotides (iNTPs) and guanosine tetra/penta phosphate (p)ppGpp], either by strengthening or by weakening of the RNA polymerase (RNAP)-promoter interactions during initiation. Studies in Escherichia coli revealed the importance of a sequence termed discriminator, located between -10 and the transcription start site of the responsive promoters in this mode of regulation. Instability of the open complex at these promoters is attributed to the lack of stabilizing interactions between the suboptimal discriminator and the 1.2 region of sigma 70 (Sig70) in RNAP holoenzyme. We demonstrate a different pattern of interaction between the promoters and sigma A (SigA) of Mycobacterium tuberculosis to execute similar regulation. Instead of cytosine and methionine, thymine at three nucleotides downstream to -10 element and leucine 232 in SigA are found to be essential for iNTPs and pppGpp mediated response at the rrn and gyr promoters of the organism. The specificity of the interaction is substantiated by mutational replacements, either in the discriminator or in SigA, which abolish the nucleotide mediated regulation in vitro or in vivo. Specific yet distinct bases and the amino acids appear to have co-evolved' to retain the discriminator-sigma 1.2 region regulatory switch operated by iNTPs/pppGpp during the transcription initiation in different bacteria.

Identification and characterization of novel indole based small molecules as anticancer agents through SIRT1 inhibition

In our pursuit to develop new potential anticancer leads, we designed a combination of structural units of indole and substituted triazole; and a library of 1-{1-methyl-2-4-phenyl-5-(propan-2-ylsulfanyl)-4H-1,2,4-triazol-3-yl ]-1H-indol-3-yl}methanamine derivatives was synthesized and characterized. Cytotoxic evaluations of these molecules over a panel of three human cancer cell lines were carried out. Few molecules exhibited potent growth inhibitory action against the treated cancer cell lines at lower micro molar concentration. An in vitro assay investigation of these active compounds using recombinant human SIRT1 enzyme showed that one of the compounds (IT-14) inhibited the deacetylation activity of the enzyme. The in vivo study of IT-14 exemplified its promising action by reducing the prostate weight to the body weight ratio in prostate hyperplasia animal models. A remarkable decrease in the disruption of histoarchitecture of the prostate tissues isolated from IT-14 treated animal compared to that of the positive control was observed. The molecular interactions with SIRT1 enzyme were also supported by molecular docking simulations. Hence this compound can act as a lead molecule to treat prostatic hyperplasia. (C) 2013 Elsevier Masson SAS. All rights reserved.

Transonic flutter, shocks, and parameter effects

There is a drop in the flutter boundary of an aeroelastic system placed in a transonic flow due to compressibility effects and is known as the transonic dip. Viscous effects can shift the lo-cation of the shock and depending on the shock strength the boundary layer may separate leading to changes in the flutter speed. An unsteady Euler flow solver coupled with the structural dynamic equations is used to understand the effect of shock on the transonic dip. The effect of various system parameters such as mass ratio, location of the center of mass, position of the elastic axis, ratio of uncoupled natural frequencies in heave and pitch are also studied. Steady turbulent flow results are presented to demonstrate the effect of viscosity on the location and strength of the shock.

Evaluation of the accuracy of an impact load cell using lumped parameter modeling and analysis

The objective of the current study is to evaluate the fidelity of load cell reading during impact testing in a drop-weight impactor using lumped parameter modeling. For the most common configuration of a moving impactor-load cell system in which dynamic load is transferred from the impactor head to the load cell, a quantitative assessment is made of the possible discrepancy that can result in load cell response. A 3-DOF (degrees-of-freedom) LPM (lumped parameter model) is considered to represent a given impact testing set-up. In this model, a test specimen in the form of a steel hat section similar to front rails of cars is represented by a nonlinear spring while the load cell is assumed to behave in a linear manner due to its high stiffness. Assuming a given load-displacement response obtained in an actual test as the true behavior of the specimen, the numerical solution of the governing differential equations following an implicit time integration scheme is shown to yield an excellent reproduction of the mechanical behavior of the specimen thereby confirming the accuracy of the numerical approach. The spring representing the load cell, however,predicts a response that qualitatively matches the assumed load-displacement response of the test specimen with a perceptibly lower magnitude of load.

Morphological Effects of G-Quadruplex Stabilization Using a Small Molecule in Zebrafish

Zebrafish (Danio rerio) embryos are transparent and advantageous for studying early developmental changes due to ex utero development, making them an appropriate model for studying gene expression changes as a result of molecular targeting. Zebrafish embryos were injected with a previously reported G-quadruplex selective ligand, and the phenotypic changes were recorded. We report marked discrepancies in the development of intersegmental vessels. In silico analysis determined that the putative G-quadruplex motif occur in the upstream promoter region of the Cdh5 (N-cadherin) gene. A real-time polymerase chain reaction-based investigation indicated that in zebrafish, CDH-2 (ZN-cad) was significantly downregulated in the ligand-treated embryos. Biophysical characterization of the interaction of the ligand with the G-quadruplex motif found in this promoter yielded strong binding and stabilization of the G-quadruplex with this ligand. Hence, we report for the first time the phenotypic impact of G-quadruplex targeting with a ligand in a vertebrate organism. This study has unveiled not only G-quadruplex targeting in non-human animal species but also the potential that G-quadruplexes can provide a ready tool for understanding the phenotypic effects of targeting certain important genes involved in differentiation and developmental processes in a living eukaryotic organism.

Charge and color breaking constraints in MSSM after the Higgs discovery at LHC

We revisit the constraints on the parameter space of the Minimal Supersymmetric Standard Model (MSSM), from charge and color breaking minima in the light of information on the Higgs from the LHC so far. We study the behavior of the scalar potential keeping two light sfermion fields along with the Higgs in the pMSSM framework and analyze the stability of the vacuum. We find that for lightest stops a parts per thousand(2) 1 TeV and small mu a parts per thousand(2) 500 GeV, the absolute stability of the potential can be attained only for . The bounds become stronger for larger values of the mu parameter. Note that this is approximately the value of Xt which maximizes the Higgs mass. Our bounds on the low scale MSSM parameters are more stringent than those reported earlier in literature. We reanalyze the stau sector as well, keeping both staus. We study the connections between the observed Higgs rates and vacuum (meta)stability. We show how a precision study of the ratio of signal strengths, (mu (gamma gamma) /mu (ZZ) ) can shed further light.

Successful data recovery from oscillation photographs containing strong polycrystalline diffraction rings from an unknown small-molecule contaminant: preliminary structure solution of Salmonella typhimurium pyridoxal kinase (PdxK)

Pyridoxal kinase (PdxK; EC 2.7.1.35) belongs to the phosphotransferase family of enzymes and catalyzes the conversion of the three active forms of vitamin B-6, pyridoxine, pyridoxal and pyridoxamine, to their phosphorylated forms and thereby plays a key role in pyridoxal 5 `-phosphate salvage. In the present study, pyridoxal kinase from Salmonella typhimurium was cloned and overexpressed in Escherichia coli, purified using Ni-NTA affinity chromatography and crystallized. X-ray diffraction data were collected to 2.6 angstrom resolution at 100 K. The crystal belonged to the primitive orthorhombic space group P2(1)2(1)2(1), with unitcell parameters a = 65.11, b = 72.89, c = 107.52 angstrom. The data quality obtained by routine processing was poor owing to the presence of strong diffraction rings caused by a polycrystalline material of an unknown small molecule in all oscillation images. Excluding the reflections close to powder/polycrystalline rings provided data of sufficient quality for structure determination. A preliminary structure solution has been obtained by molecular replacement with the Phaser program in the CCP4 suite using E. coli pyridoxal kinase (PDB entry 2ddm) as the phasing model. Further refinement and analysis of the structure are likely to provide valuable insights into catalysis by pyridoxal kinases.

Strategies for high efficiency and stability in biogas-fuelled small engines

This work assesses the performance of small biogas-fuelled engines and explores high-efficiency strategies for power generation in the very low power range of less than 1000 W. Experiments were performed on a small 95-cc, single-cylinder, four-stroke spark-ignition engine operating on biogas. The engine was operated in two modes, i.e., `premixed' and `fuel injection' modes, using both single and dual spark plug configurations. Measurements of in-cylinder pressure, crank angle, brake power, air and fuel flow rates, and exhaust emissions were conducted. Cycle-to-cycle variations in engine in-cylinder pressure and power were also studied and assessed quantitatively for various loading conditions. Results suggest that biogas combustion can be fairly sensitive to the ignition strategies thereby affecting the power output and efficiency. Further, results indicate that continuous fuel injection shows superior performance compared to the premixed case especially at low loads owing to possible charge stratification in the engine cylinder. Overall, this study has demonstrated for the first time that a combination of technologies such as lean burn, fuel injection, and dual spark plug ignition can provide highly efficient and stable operation in a biogas-fuelled small S.I. engine, especially in the low power range of 450-1000W. (C) 2014 Elsevier Inc. All rights reserved.

Relation between the Isentropic Index and the Gruneisen Parameter for Saturated Liquids

We investigate the isentropic index along the saturated vapor line as a correlating parameter with quantities both in the saturated liquid phase and the saturated vapor phase. The relation is established via temperatures such as T-hgmax and T* where the saturated vapor enthalpy and the product of saturation temperature and saturated liquid density attain a maximum, respectively. We obtain that the saturated vapor isentropic index is correlated with these temperatures but also with the saturated liquid Gruneisen parameters at T-hgmax. and T*.

Fluctuating micro-heterogeneity in water-tert-butyl alcohol mixtures and lambda-type divergence of the mean cluster size with phase transition-like multiple anomalies

Water-tert-butyl alcohol (TBA) binary mixture exhibits a large number of thermodynamic and dynamic anomalies. These anomalies are observed at surprisingly low TBA mole fraction, with x(TBA) approximate to 0.03-0.07. We demonstrate here that the origin of the anomalies lies in the local structural changes that occur due to self-aggregation of TBA molecules. We observe a percolation transition of the TBA molecules at x(TBA) approximate to 0.05. We note that ``islands'' of TBA clusters form even below this mole fraction, while a large spanning cluster emerges above that mole fraction. At this percolation threshold, we observe a lambda-type divergence in the fluctuation of the size of the largest TBA cluster, reminiscent of a critical point. Alongside, the structure of water is also perturbed, albeit weakly, by the aggregation of TBA molecules. There is a monotonic decrease in the tetrahedral order parameter of water, while the dipole moment correlation shows a weak nonlinearity. Interestingly, water molecules themselves exhibit a reverse percolation transition at higher TBA concentration, x(TBA) approximate to 0.45, where large spanning water clusters now break-up into small clusters. This is accompanied by significant divergence of the fluctuations in the size of largest water cluster. This second transition gives rise to another set of anomalies around. Both the percolation transitions can be regarded as manifestations of Janus effect at small molecular level. (C) 2014 AIP Publishing LLC.

Small molecule inhibitors of HCV replication from Pomegranate

Hepatitis C virus (HCV) is the causative agent of end-stage liver disease. Recent advances in the last decade in anti HCV treatment strategies have dramatically increased the viral clearance rate. However, several limitations are still associated, which warrant a great need of novel, safe and selective drugs against HCV infection. Towards this objective, we explored highly potent and selective small molecule inhibitors, the ellagitannins, from the crude extract of Pomegranate (Punica granatum) fruit peel. The pure compounds, punicalagin, punicalin, and ellagic acid isolated from the extract specifically blocked the HCV NS3/4A protease activity in vitro. Structural analysis using computational approach also showed that ligand molecules interact with the catalytic and substrate binding residues of NS3/4A protease, leading to inhibition of the enzyme activity. Further, punicalagin and punicalin significantly reduced the HCV replication in cell culture system. More importantly, these compounds are well tolerated ex vivo and `no observed adverse effect level' (NOAEL) was established upto an acute dose of 5000 mg/kg in BALB/c mice. Additionally, pharmacokinetics study showed that the compounds are bioavailable. Taken together, our study provides a proof-of-concept approach for the potential use of antiviral and non-toxic principle ellagitannins from pomegranate in prevention and control of HCV induced complications.

Study of liquid fuel transport in a small carburetted engine in the context of cold-start HC emission control

In the present study, a detailed visualization of the transport of fuel film has been performed in a small carburetted engine with a transparent manifold at the exit of the carburettor. The presence of fuel film is observed significantly on the lower half of the manifold at idling, while at load conditions, the film is found to be distributed all throughout the manifold walls. Quantitative measurement of the fuel film in a specially-designed manifold of square cross section has also been performed using the planar laser-induced fluorescence (PLIF) technique. The measured fuel film thickness is observed to be of the order of 1 nun at idling, and in the range of 0.1 to 0.4 mm over the range of load and speed studied. These engine studies are complemented by experiments conducted in a carburettor rig to study the state of the fuel exiting the carburettor. Laser-based Particle/Droplet Image Analysis (PDIA) technique is used to identify fuel droplets and ligaments and estimate droplet diameters. At a throttle position corresponding to idling, the fuel exiting the carburettor is found to consist of very fine droplets of size less than 15 mu m and large fuel ligaments associated with length scales of the order of 500 mu m and higher. For a constant pressure difference across the carburettor, the fuel consists of droplets with an SMD of the order of 30 mu m. Also, the effect of liquid fuel film on the cold start HC emissions is studied. Based on the understanding obtained from these studies, strategies such as manifold heating and varying carburettor main jet nozzle diameter are implemented. These are observed to reduce emissions under both idling and varying load conditions.

Small strong epsilon nets

Let P be a set of n points in R-d. A point x is said to be a centerpoint of P if x is contained in every convex object that contains more than dn/d+1 points of P. We call a point x a strong centerpoint for a family of objects C if x is an element of P is contained in every object C is an element of C that contains more than a constant fraction of points of P. A strong centerpoint does not exist even for halfspaces in R-2. We prove that a strong centerpoint exists for axis-parallel boxes in Rd and give exact bounds. We then extend this to small strong epsilon-nets in the plane. Let epsilon(S)(i) represent the smallest real number in 0, 1] such that there exists an epsilon(S)(i)-net of size i with respect to S. We prove upper and lower bounds for epsilon(S)(i) where S is the family of axis-parallel rectangles, halfspaces and disks. (C) 2014 Elsevier B.V. All rights reserved.

TRANSIENT NATURAL CONVECTION FLOW IN A RECTANGULAR CAVITY FILLED WITH A POROUS MATERIAL WITH LOCALIZED HEATING FROM BELOW AND THERMAL STRATIFICATION

The transient natural convection flow with thermal stratification in a rectangular cavity filled with fluid saturated porous medium obeying Darcy's law has been studied. Prior to the time t* = 0, the flow in the cavity is assumed to be motionless and all four walls of the cavity are at the same constant temperature. At time t* = 0, the temperatures of the vertical walls are suddenly increased which vary linearly with the distance y and at the same time on the bottom wall an isothermal heat source is placed centrally. This sudden change in the wall temperatures gives rise to unsteadiness in the problem. The horizontal temperature difference induces and sustains a buoyancy driven flow in the cavity which is then controlled by the vertical temperature difference. The partial differential equations governing the transient natural convection flow have been solved numerically. The local and average Nusselt numbers decrease rapidly in a small time interval after the start of the impulsive change in the wall temperatures and the steady state is reached quickly. The time required to reach the steady state depends on the Rayleigh number and the thermal stratification parameter.