Investigating the mechanism of acoustically activated uptake of drugs from Pluronic micelles

BACKGROUND: This paper examines the mechanism of ultrasonic enhanced drug delivery from Pluronic micelles. In previous publications by our group, fluorescently labeled Pluronic was shown to penetrate HL-60 cells with and without the action of ultrasound, while drug uptake was increased with the application of ultrasound. METHODS: In this study, the amount of uptake of two fluorescent probes, Lysosensor Green (a pH-sensitive probe) and Cell Tracker Orange CMTMR (a pH-independent probe), was measured in HL-60 and HeLa cells. RESULTS: The results of our experiments show that the increase in drug accumulation in the cells as a result of ultrasonication is not due to an increase in endocytosis due to ultrasonication. CONCLUSIONS: We hypothesize that sonoporation plays an important role in the acoustically activated drug delivery of chemotherapy drugs delivered from Pluronic micelles

Asymmetry of the natural line profile for the hydrogen atom

The asymmetry of the natural line profile for transitions in hydrogen-like atoms is evaluated within a QED framework. For the Lyman-alpha $1s-2p$ absorption transition in neutral hydrogen this asymmetry results in an additional energy shift of 2.929856 Hz. For the $2s_{1/2}-2p_{3/2}$ transition it amounts to -1.512674 Hz. As a new feature this correction turns out to be process dependent. The quoted numbers refer to the Compton-scattering process.Comment: RevTex, 7 Latex pages, 1 figur

Quantization of the Riemann Zeta-Function and Cosmology

Quantization of the Riemann zeta-function is proposed. We treat the Riemann zeta-function as a symbol of a pseudodifferential operator and study the corresponding classical and quantum field theories. This approach is motivated by the theory of p-adic strings and by recent works on stringy cosmological models. We show that the Lagrangian for the zeta-function field is equivalent to the sum of the Klein-Gordon Lagrangians with masses defined by the zeros of the Riemann zeta-function. Quantization of the mathematics of Fermat-Wiles and the Langlands program is indicated. The Beilinson conjectures on the values of L-functions of motives are interpreted as dealing with the cosmological constant problem. Possible cosmological applications of the zeta-function field theory are discussed.Comment: 14 pages, corrected typos, references and comments adde

Ground-based acoustic parametric generator impact on the atmosphere and ionosphere in an active experiment

We develop theoretical basics of active experiments with two beams of acoustic waves, radiated by a ground-based sound generator. These beams are transformed into atmospheric acoustic gravity waves (AGWs), which have parameters that enable them to penetrate to the altitudes of the ionospheric E and F regions where they influence the electron concentration of the ionosphere. Acoustic waves are generated by the ground-based parametric sound generator (PSG) at the two close frequencies. The main idea of the experiment is to design the output parameters of the PSG to build a cascade scheme of nonlinear wave frequency downshift transformations to provide the necessary conditions for their vertical propagation and to enable penetration to ionospheric altitudes. The PSG generates sound waves (SWs) with frequencies f1 = 600 and f2 = 625 Hz and large amplitudes (100-420ms-1). Each of these waves is modulated with the frequency of 0.016 Hz. The novelty of the proposed analytical-numerical model is due to simultaneous accounting for nonlinearity, diffraction, losses, and dispersion and inclusion of the two-stage transformation (1) of the initial acoustic waves to the acoustic wave with the difference frequency Δf = f2 - f1 in the altitude ranges 0-0.1 km, in the strongly nonlinear regime, and (2) of the acoustic wave with the difference frequency to atmospheric acoustic gravity waves with the modulational frequency in the altitude ranges 0.1-20 km, which then reach the altitudes of the ionospheric E and F regions, in a practically linear regime. AGWs, nonlinearly transformed from the sound waves, launched by the two-frequency ground-based sound generator can increase the transparency of the ionosphere for the electromagnetic waves in HF (MHz) and VLF (kHz) ranges. The developed theoretical model can be used for interpreting an active experiment that includes the PSG impact on the atmosphere-ionosphere system, measurements of electromagnetic and acoustic fields, study of the variations in ionospheric transparency for the radio emissions from galactic radio sources, optical measurements, and the impact on atmospheric aerosols. The proposed approach can be useful for better understanding the mechanism of the acoustic channel of seismo-ionospheric coupling

The UN in the lab

We consider two alternatives to inaction for governments combating terrorism, which we term Defense and Prevention. Defense consists of investing in resources that reduce the impact of an attack, and generates a negative externality to other governments, making their countries a more attractive objective for terrorists. In contrast, Prevention, which consists of investing in resources that reduce the ability of the terrorist organization to mount an attack, creates a positive externality by reducing the overall threat of terrorism for all. This interaction is captured using a simple 3×3 “Nested Prisoner’s Dilemma” game, with a single Nash equilibrium where both countries choose Defense. Due to the structure of this interaction, countries can benefit from coordination of policy choices, and international institutions (such as the UN) can be utilized to facilitate coordination by implementing agreements to share the burden of Prevention. We introduce an institution that implements a burden-sharing policy for Prevention, and investigate experimentally whether subjects coordinate on a cooperative strategy more frequently under different levels of cost sharing. In all treatments, burden sharing leaves the Prisoner’s Dilemma structure and Nash equilibrium of the game unchanged. We compare three levels of burden sharing to a baseline in a between-subjects design, and find that burden sharing generates a non-linear effect on the choice of the efficient Prevention strategy and overall performance. Only an institution supporting a high level of mandatory burden sharing generates a significant improvement in the use of the Prevention strategy

Uniformizing the Stacks of Abelian Sheaves

Elliptic sheaves (which are related to Drinfeld modules) were introduced by Drinfeld and further studied by Laumon--Rapoport--Stuhler and others. They can be viewed as function field analogues of elliptic curves and hence are objects "of dimension 1". Their higher dimensional generalisations are called abelian sheaves. In the analogy between function fields and number fields, abelian sheaves are counterparts of abelian varieties. In this article we study the moduli spaces of abelian sheaves and prove that they are algebraic stacks. We further transfer results of Cerednik--Drinfeld and Rapoport--Zink on the uniformization of Shimura varieties to the setting of abelian sheaves. Actually the analogy of the Cerednik--Drinfeld uniformization is nothing but the uniformization of the moduli schemes of Drinfeld modules by the Drinfeld upper half space. Our results generalise this uniformization. The proof closely follows the ideas of Rapoport--Zink. In particular, analogies of $p$-divisible groups play an important role. As a crucial intermediate step we prove that in a family of abelian sheaves with good reduction at infinity, the set of points where the abelian sheaf is uniformizable in the sense of Anderson, is formally closed.Comment: Final version, appears in "Number Fields and Function Fields - Two Parallel Worlds", Papers from the 4th Conference held on Texel Island, April 2004, edited by G. van der Geer, B. Moonen, R. Schoo

Enhanced inverse bremsstrahlung heating rates in a strong laser field

Test particle studies of electron scattering on ions, in an oscillatory electromagnetic field have shown that standard theoretical assumptions of small angle collisions and phase independent orbits are incorrect for electron trajectories with drift velocities smaller than quiver velocity amplitude. This leads to significant enhancement of the electron energy gain and the inverse bremsstrahlung heating rate in strong laser fields. Nonlinear processes such as Coulomb focusing and correlated collisions of electrons being brought back to the same ion by the oscillatory field are responsible for large angle, head-on scattering processes. The statistical importance of these trajectories has been examined for mono-energetic beam-like, Maxwellian and highly anisotropic electron distribution functions. A new scaling of the inverse bremsstrahlung heating rate with drift velocity and laser intensity is discussed.Comment: 12 pages, 12 figure

On a Conjecture of Rapoport and Zink

In their book Rapoport and Zink constructed rigid analytic period spaces $F^{wa}$ for Fontaine's filtered isocrystals, and period morphisms from PEL moduli spaces of $p$-divisible groups to some of these period spaces. They conjectured the existence of an \'etale bijective morphism $F^a \to F^{wa}$ of rigid analytic spaces and of a universal local system of $Q_p$-vector spaces on $F^a$. For Hodge-Tate weights $n-1$ and $n$ we construct in this article an intrinsic Berkovich open subspace $F^0$ of $F^{wa}$ and the universal local system on $F^0$. We conjecture that the rigid-analytic space associated with $F^0$ is the maximal possible $F^a$, and that $F^0$ is connected. We give evidence for these conjectures and we show that for those period spaces possessing PEL period morphisms, $F^0$ equals the image of the period morphism. Then our local system is the rational Tate module of the universal $p$-divisible group and enjoys additional functoriality properties. We show that only in exceptional cases $F^0$ equals all of $F^{wa}$ and when the Shimura group is $GL_n$ we determine all these cases.Comment: v2: 48 pages; many new results added, v3: final version that will appear in Inventiones Mathematica