Modeling the Effects of Drug Binding on the Dynamic Instability of Microtubules

We propose a stochastic model that accounts for the growth, catastrophe and rescue processes of steady state microtubules assembled from MAP-free tubulin. Both experimentally and theoretically we study the perturbation of microtubule dynamic instability by S-methyl-D-DM1, a synthetic derivative of the microtubule-targeted agent maytansine and a potential anticancer agent. We find that to be an effective suppressor of microtubule dynamics a drug must primarily suppress the loss of GDP tubulin from the microtubule tip.Comment: 17 pages, 11 figures, to appear in Phys. Bio

Lattice extraction of K→ππ K \to \pi \pi amplitudes to NLO in partially quenched and in full chiral perturbation theory

We show that it is possible to construct $\epsilon^\prime/\epsilon$ to NLO using partially quenched chiral perturbation theory (PQChPT) from amplitudes that are computable on the lattice. We demonstrate that none of the needed amplitudes require three-momentum on the lattice for either the full theory or the partially quenched theory; non-degenerate quark masses suffice. Furthermore, we find that the electro-weak penguin ($\Delta I=3/2$ and 1/2) contributions to $\epsilon^\prime/\epsilon$ in PQChPT can be determined to NLO using only degenerate ($m_K=m_\pi$) $K\to\pi$ computations without momentum insertion. Issues pertaining to power divergent contributions, originating from mixing with lower dimensional operators, are addressed. Direct calculations of $K\to\pi\pi$ at unphysical kinematics are plagued with enhanced finite volume effects in the (partially) quenched theory, but in simulations when the sea quark mass is equal to the up and down quark mass the enhanced finite volume effects vanish to NLO in PQChPT. In embedding the QCD penguin left-right operator onto PQChPT an ambiguity arises, as first emphasized by Golterman and Pallante. With one version (the "PQS") of the QCD penguin, the inputs needed from the lattice for constructing $K\to\pi\pi$ at NLO in PQChPT coincide with those needed for the full theory. Explicit expressions for the finite logarithms emerging from our NLO analysis to the above amplitudes are also given.Comment: 54 pages, 3 figures; Important revisions: Corrections to formulas for K->pi pi with degenerate quark masses have been mad

Cloud condensation nuclei activity of six pollenkitts and the influence of their surface activity

The role of surfactants in governing water interactions of atmospheric aerosols has been a recurring topic in cloud microphysics for more than two decades. Studies of detailed surface thermodynamics are limited by the availability of aerosol samples for experimental analysis and incomplete validation of various proposed Kohler model frameworks for complex mixtures representative of atmospheric aerosol. Pollenkitt is a viscous material that coats grains of pollen and plays important roles in pollen dispersion and plant reproduction. Previous work suggests that it may also be an important contributor to pollen water uptake and cloud condensation nuclei (CCN) activity. The chemical composition of pollenkitt varies between species but has been found to comprise complex organic mixtures including oxygenated, lipid, and aliphatic functionalities. This mix of functionalities suggests that pollenkitt may display aqueous surface activity, which could significantly impact pollen interactions with atmospheric water. Here, we study the surface activity of pollenkitt from six different species and its influence on pollenkitt hygroscopicity. We measure cloud droplet activation and concentration-dependent surface tension of pollenkitt and its mixtures with ammonium sulfate salt. Experiments are compared to predictions from several thermodynamic models, taking aqueous surface tension reduction and surfactant surface partitioning into account in various ways. We find a clear reduction of surface tension by pollenkitt in aqueous solution and evidence for impact of both surface tension and surface partitioning mechanisms on cloud droplet activation potential and hygroscopicity of pollenkitt particles. In addition, we find indications of complex nonideal solution effects in a systematic and consistent dependency of pollenkitt hygroscopicity on particle size. The impact of pollenkitt surface activity on cloud microphysics is different from what is observed in previous work for simple atmospheric surfactants and more resembles recent observations for complex primary and secondary organic aerosol, adding new insight to our understanding of the multifaceted role of surfactants in governing aerosol-water interactions. We illustrate how the explicit characterization of pollenkitt contributions provides the basis for modeling water uptake and cloud formation of pollen and their fragments over a wide range of atmospheric conditions.Peer reviewe

Vulnerability of the frontal-temporal connections in temporal lobe epilepsy.

ObjectiveIn temporal lobe epilepsy (TLE), frontal-temporal connections are integral parts of the epileptogenic network. Although frontal-temporal gray matter abnormalities have been consistently demonstrated in TLE, white matter connections between these two lobes require further study in this disease setting. We therefore investigated the integrity of two major frontal-temporal white matter association tracts, uncinate fasciculus (UF) and arcuate fasciculus (AF), and their clinical correlates.MethodsUsing diffusion tensor imaging (DTI) tractography, integrity of the UF and AF was examined in 22 individuals (12 subjects with TLE and 10 age-matched healthy controls). DTI indices of these tracts were compared between the two subject groups and correlates examined with clinical variables that included age of seizure onset, duration of epilepsy, history of febrile seizure and antiepileptic medication exposure.ResultsIn subjects with TLE, the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of UF and AF ipsilateral to the side of seizure onset were abnormal when compared to healthy controls. Furthermore, lower UF FA correlated with earlier age of seizure onset.ConclusionTLE is associated with abnormal integrity of frontal-temporal white matter tracts, but only on the side of seizure onset. This suggests that frontal-temporal white matter tracts are vulnerable to recurrent seizures and/or the factors precipitating the epilepsy

UV-light-driven prebiotic synthesis of iron–sulfur clusters

Iron–sulfur clusters are ancient cofactors that play a fundamental role in metabolism and may have impacted the prebiotic chemistry that led to life. However, it is unclear whether iron–sulfur clusters could have been synthesized on prebiotic Earth. Dissolved iron on early Earth was predominantly in the reduced ferrous state, but ferrous ions alone cannot form polynuclear iron–sulfur clusters. Similarly, free sulfide may not have been readily available. Here we show that UV light drives the synthesis of [2Fe–2S] and [4Fe–4S] clusters through the photooxidation of ferrous ions and the photolysis of organic thiols. Iron–sulfur clusters coordinate to and are stabilized by a wide range of cysteine-containing peptides and the assembly of iron–sulfur cluster-peptide complexes can take place within model protocells in a process that parallels extant pathways. Our experiments suggest that iron–sulfur clusters may have formed easily on early Earth, facilitating the emergence of an iron–sulfur-cluster-dependent metabolism

Whispering gallery mode enhanced optical force with resonant tunneling excitation in the Kretschmann geometry

The boundary element method is applied to investigate the optical forces when whispering gallery modes (WGMs) are excited by a total internally reflected wave. Such evanescent wave is particularly effective in exciting the high-$Q$ WGM, while the low angular or high radial order modes are suppressed relatively. This results in a large contrast between the forces on and off resonance, and thus allows for high size-selectivity. We fully incorporate the prism-particle interaction and found that the optical force behaves differently at different separations. Optimal separation is found which corresponds to a compromise between intensity and $Q$ factor.Comment: 4 pages, 3 figure

Nitric acid scavenging by mineral and biomass burning aerosols

The abundance of gas phase nitric acid in the upper troposphere is overestimated by global chemistry-transport models, especially during the spring and summer seasons. Recent aircraft data obtained over the central US show that mineral aerosols were abundant in the upper troposphere during spring. Chemical reactions on mineral dust may provide an important sink for nitric acid. In regions where the mineral dust abundance is low in the upper troposphere similar HNO3 removal processes may occur on biomass burning aerosols. We propose that mineral and biomass burning aerosols may provide an important global sink for gas phase nitric acid, particularly during spring and summer when aerosol composition in the upper troposphere may be greatly affected by dust storms from east Asia or tropical biomass burning plumes

Turbulence spectra in the buoyancy subrange of thermally stratified shear flows

CER68-69JTL21.February 1969.Originally presented as the author's thesis, Colorado State University.Includes bibliographical references (pages 94-97).Prepared under Office of Naval Research, project no. NR 062-414/6-6-68(Code 438), U.S. Department of Defense.A generalized eddy-viscosity approximation is used to study the turbulence spectra of thermally stratified shear flows. For a stationary process in the wave number range investigated--the buoyancy subrange--under the assumption of local homogeneity of the flow, two governing spectral equations with six unknowns are derived from the equations of motion and energy. In order to reduce the number of unknowns to two so that the spectral equations can be solved, a generalized eddy-viscosity is used for expressing the integrated forms of the inertial transfers of energy and temperature inhomogeneity, the shear stress and vertical heat flux in terms of velocity spectrum ¢(k) and temperature spectrum ¢TT(k). Asymptotic solutions are obtained in the buoyancy subrange where the local production and local dissipation of turbulent energy is negligible as compared to the inertial transfer and vertical heat flux terms when the flow conditions satisfy the criterion ε|dT'/dz| << N g/T' or g/T'. |dT'/dz| << N/ε.(g/T)^2. In the buoyancy subrange of stably stratified turbulent flow, the power law for the velocity and temperature spectra is not universal but varies with the flow conditions in the way ¢(k) ~ k^n and ¢TT(k) ~ k^m where 11/5 ≥ n ≥ -3 and -1 ≥ m ≥ -7/5. According to the measurements of velocity spectra in the atmosphere (Pinus and Schcherbakova, 1966; Myrup, 1968), the dependence of the power law on the flow conditions was confirmed. The solutions of Bolgiano (1959) and Luialey-Shur (1964) are only two particular cases of the present results under cert ain flow conditions. In the case of the unstably stratified turbulent flow, the velocity spectrum exhibits a hump in the buoyancy subrange as a result of the energy input from the temperature field to the velocity field. In the left side of this hump the velocity spectrum approaches a +1 slope and the temperature spectrum shows a -3 slope. The measurements of the velocity spectra in the atmosphere (Ivanov and Ordanovich, 1967) confirms this tendency.Under contract no. N00014-68-A-0493-0001