Ion dynamics and coherent structure formation following laser pulse self-channeling

The propagation of a superintense laser pulse in an underdense, inhomogeneous plasma has been studied numerically by two-dimensional particle-in-cell simulations on a time scale extending up to several picoseconds. The effects of the ion dynamics following the charge-displacement self-channeling of the laser pulse have been addressed. Radial ion acceleration leads to the ``breaking'' of the plasma channel walls, causing an inversion of the radial space-charge field and the filamentation of the laser pulse. At later times a number of long-lived, quasi-periodic field structures are observed and their dynamics is characterized with high resolution. Inside the plasma channel, a pattern of electric and magnetic fields resembling both soliton- and vortex-like structures is observed.Comment: 10 pages, 5 figures (visit http://www.df.unipi.it/~macchi to download a high-resolution version), to appear in Plasma Physics and Controlled Fusion (Dec. 2007), special issue containing invited papers from the 34th EPS Conference on Plasma Physics (Warsaw, July 2007

Resistance to novel drug classes

Understanding the mechanisms that underlie resistance development to novel drugs is essential to a better clinical management of resistant viruses and to prevent further resistance development and spread. RECENT FINDINGS: Integrase inhibitors and CCR5 antagonists are the more recent antiretroviral classes developed. The HIV-1 integrase, responsible for the chromosomal integration of the newly synthesized double-stranded viral DNA into the host genomic DNA, represents a new and important target; and two integrase inhibitors (INIs), raltegravir and elvitegravir, have been shown promising results in clinical trials. Viral entry is also an attractive step for the development of new drugs against HIV variants resistant to current antiretroviral drugs, and two CCR5 antagonists have been designed to inhibit HIV-1 binding to R5 co-receptor and are under clinical investigation. SUMMARY: Drug resistance to INIs occurs through the selection of mutations within HIV integrase. The kinetic of selection seems rapid and one mutation alone is able to confer resistance to integrase inhibitor, suggesting that this class of drug has a low genetic barrier. Two ways could explain the failure of the CCR5 antagonist class: a rapid outgrowth of pre-existing archived X4 virus or the selection of a resistance to CCR5 antagonists through amino acid changes in V

Charged State of a Spherical Plasma in Vacuum

The stationary state of a spherically symmetric plasma configuration is investigated in the limit of immobile ions and weak collisions. Configurations with small radii are positively charged as a significant fraction of the electron population evaporates during the equilibration process, leaving behind an electron distribution function with an energy cutoff. Such charged plasma configurations are of interest for the study of Coulomb explosions and ion acceleration from small clusters irradiated by ultraintense laser pulses and for the investigation of ion bunches propagation in a plasma

Harmonic generation by atoms in circularly polarized two-color laser fields with coplanar polarizations and commensurate frequencies

The generation of harmonics by atoms or ions in a two-color, coplanar field configuration with commensurate frequencies is investigated through both, an analytical calculation based on the Lewenstein model and the numerical ab initio solution of the time-dependent Schroedinger equation of a two-dimensional model ion. Through the analytical model, selection rules for the harmonic orders in this field configuration, a generalized cut-off for the harmonic spectra, and an integral expression for the harmonic dipole strength is provided. The numerical results are employed to test the predictions of the analytical model. The scaling of the cut-off as a function of both, one of the laser intensities and frequency ratio $\eta$, as well as entire spectra for different $\eta$ and laser intensities are presented and analyzed. The theoretical cut-off is found to be an upper limit for the numerical results. Other discrepancies between analytical model and numerical results are clarified by taking into account the probabilities of the absorption processes involved.Comment: 8 figure

The multifactorial pathways towards resistance to the cytosine analogues emtricitabine and lamivudine: Evidences from literature

The article by Bulteel et al.,1 published in the September issue of the journal, has investigated the rate of M184V emergence in patients receiving HAART combinations containing efavirenz (EFV), tenofovir (TDF) and lamivudine (3 TC) or emtricitabine (FTC) within the UK Collaborative HIV Cohort. By analyzing 304 genotypic resistance tests, the authors asserted that, although patients receiving 3 TC-based regimens were more likely to develop M184V than those receiving FTC-based regimens (event rate: 0.55 [95%CI: 0.28–0.96] for 3 TC versus 0.34 [95%CI: 0.21–0.46] for FTC), this association was not statistically significant in both univariable and multivariable models. These results are different from those reported in previous studies from our and other groups2, 3 and 4 showing a significant decrease in M184V emergence in patients failing FTC + TDF-based compared to 3 TC + TDF-based HAART (Table 1). The lower prevalence of M184V in FTC-containing regimen was also supported by a recently published letter showing a strong trend (P = 0.051) towards higher rates of resistance to the 3 TC containing regimen 5.5 (1.8–12.8) per 1000 patient years when compared with the FTC containing regimens 1.7 (0.8–3.2) per 1000 patient year

Conjugacy in Baumslag's group, generic case complexity, and division in power circuits

The conjugacy problem belongs to algorithmic group theory. It is the following question: given two words x, y over generators of a fixed group G, decide whether x and y are conjugated, i.e., whether there exists some z such that zxz^{-1} = y in G. The conjugacy problem is more difficult than the word problem, in general. We investigate the complexity of the conjugacy problem for two prominent groups: the Baumslag-Solitar group BS(1,2) and the Baumslag(-Gersten) group G(1,2). The conjugacy problem in BS(1,2) is TC^0-complete. To the best of our knowledge BS(1,2) is the first natural infinite non-commutative group where such a precise and low complexity is shown. The Baumslag group G(1,2) is an HNN-extension of BS(1,2). We show that the conjugacy problem is decidable (which has been known before); but our results go far beyond decidability. In particular, we are able to show that conjugacy in G(1,2) can be solved in polynomial time in a strongly generic setting. This means that essentially for all inputs conjugacy in G(1,2) can be decided efficiently. In contrast, we show that under a plausible assumption the average case complexity of the same problem is non-elementary. Moreover, we provide a lower bound for the conjugacy problem in G(1,2) by reducing the division problem in power circuits to the conjugacy problem in G(1,2). The complexity of the division problem in power circuits is an open and interesting problem in integer arithmetic.Comment: Section 5 added: We show that an HNN extension G = < H, b | bab^-1 = {\phi}(a), a \in A > has a non-amenable Schreier graph with respect to the base group H if and only if A \neq H \neq

Potentials and limitations of NFIs and remote sensing in the assessment of harvest rates: a reply to Breidenbach et al.

AbstractThe timely and accurate monitoring of forest resources is becoming of increasing importance in light of the multi-functionality of these ecosystems and their increasing vulnerability to climate change. Remote sensing observations of tree cover and systematic ground observations from National Forest Inventories (NFIs) represent the two major sources of information to assess forest area and use. The specificity of two methods is calling for an in-depth analysis of their strengths and weaknesses and for the design of novel methods emerging from the integration of satellite and surface data. On this specific debate, a recent paper by Breidenbach et al. published in this journal suggests that the detection of a recent increase in EU forest harvest rate—as reported in Nature by Ceccherini et al.—is largely due to technical limitations of satellite-based mapping. The article centers on the difficulty of the approaches to estimate wood harvest based on remote sensing. However, it does not discuss issues with the robustness of validation approaches solely based on NFIs. Here we discuss the use of plot data as a validation set for remote sensing products, discussing potentials and limitations of both NFIs and remote sensing, and how they can be used synergistically. Finally, we highlight the need to collect in situ data that is both relevant and compatible with remote sensing products within the European Union

Computational analysis of Human Immunodeficiency Virus (HIV) Type-1 reverse transcriptase crystallographic models based on significant conserved residues found in Highly Active Antiretroviral Therapy (HAART)-treated patients.

Reverse transcription of the viral single-stranded (+) RNA genome into double-stranded DNA is an essential step in the human immunodeficiency virus' (HIV) life-cycle. Although several viral proteins are involved in the regulation and/or efficiency of reverse transcription, the process of retroviral DNA synthesis is entirely dependent on the enzymatic activities of the retroviral reverse transcriptase enzyme (RT). Due to its crucial role in the HIV life-cycle, RT is a primary target for anti-HIV drug development. Nonetheless, drug resistance is the major problem affecting the clinical efficacy of antiretroviral agents. Incomplete pharmacological pressure represents the logical cause and not the consequence of different mutation pathways in RT associated with approved inhibitors resistance. In this review we have analyzed RT Protein Data Bank (PDB) models using our innovative computational approach “GRID Based Pharmacophore Model” (GBPM). This method was applied to clinically relevant RT conserved residues found in a large cohort of HAART treated patients. The PDB entries have been selected among the unbound and the complexed models with DNA and/or inhibitors. Such an approach has revealed itself useful to highlight the mutation effects in the drug-RT recognition as well as in the heterodimer stabilization of the enzyme. Most of the clinical and biochemical evidences already reported in the literature have been rationalized at molecular level via the GBPM computational approach. A definite future application of this method will be the identification of conserved regions of critical macromolecules, such as the HIV-1 RT, to be targeted for the development of innovative therapeutic agents

Dynamics of charge-displacement channeling in intense laser-plasma interactions

The dynamics of transient electric fields generated by the interaction of high intensity laser pulses with underdense plasmas has been studied experimentally with the proton projection imaging technique. The formation of a charged channel, the propagation of its front edge and the late electric field evolution have been characterised with high temporal and spatial resolution. Particle-in-cell simulations and an electrostatic, ponderomotive model reproduce the experimental features and trace them back to the ponderomotive expulsion of electrons and the subsequent ion acceleration.Comment: 5 figures, accepted for publication in New Journal of Physic

Shift-Symmetric Configurations in Two-Dimensional Cellular Automata: Irreversibility, Insolvability, and Enumeration

The search for symmetry as an unusual yet profoundly appealing phenomenon, and the origin of regular, repeating configuration patterns have long been a central focus of complexity science and physics. To better grasp and understand symmetry of configurations in decentralized toroidal architectures, we employ group-theoretic methods, which allow us to identify and enumerate these inputs, and argue about irreversible system behaviors with undesired effects on many computational problems. The concept of so-called configuration shift-symmetry is applied to two-dimensional cellular automata as an ideal model of computation. Regardless of the transition function, the results show the universal insolvability of crucial distributed tasks, such as leader election, pattern recognition, hashing, and encryption. By using compact enumeration formulas and bounding the number of shift-symmetric configurations for a given lattice size, we efficiently calculate the probability of a configuration being shift-symmetric for a uniform or density-uniform distribution. Further, we devise an algorithm detecting the presence of shift-symmetry in a configuration. Given the resource constraints, the enumeration and probability formulas can directly help to lower the minimal expected error and provide recommendations for system's size and initialization. Besides cellular automata, the shift-symmetry analysis can be used to study the non-linear behavior in various synchronous rule-based systems that include inference engines, Boolean networks, neural networks, and systolic arrays.Comment: 22 pages, 9 figures, 2 appendice