Ponderomotive manipulation of cold subwavelength plasmas

Ponderomotive forces (PFs) induced in cold subwavelength plasmas by an externally applied electromagnetic wave are studied analytically. To this end, the plasma is modeled as a sphere with a radially varying permittivity, and the internal electric fields are calculated by solving the macroscopic Maxwell equations using an expansion in Debye potentials. It is found that the PF is directed opposite to the plasma density gradient, similarly to large-scale plasmas. In case of a uniform density profile, a residual spherically symmetric compressive PF is found, suggesting possibilities for contactless ponderomotive manipulation of homogeneous subwavelength objects. The presence of a surface PF on discontinuous plasma boundaries is derived. This force is essential for a microscopic description of the radiation-plasma interaction consistent with momentum conservation. It is shown that the PF integrated over the plasma volume is equivalent to the radiation pressure exerted on the plasma by the incident wave. The concept of radiative acceleration of subwavelength plasmas, proposed earlier, is applied to ultracold plasmas. It is estimated that these plasmas may be accelerated to keV ion energies, resulting in a neutralized beam with a brightness comparable to that of current high-performance ion sources.Comment: 16 pages, 6 figure

Classical formulations of the electromagnetic self-force of extended charged bodies

Several noncovariant formulations of the electromagnetic self-force of extended charged bodies, as have been developed in the context of classical models of charged particles, are compared. The mathematical equivalence of the various dissimilar self-force expressions is demonstrated explicitly by deriving these expressions directly from one another. The applicability of the self-force formulations and their significance in the wider context of classical charged particle models are discussed.Comment: 21 pages, 1 figur

Heating mechanisms in radio frequency driven ultracold plasmas

Several mechanisms by which an external electromagnetic field influences the temperature of a plasma are studied analytically and specialized to the system of an ultracold plasma (UCP) driven by a uniform radio frequency (RF) field. Heating through collisional absorption is reviewed and applied to UCPs. Furthermore, it is shown that the RF field modifies the three body recombination process by ionizing electrons from intermediate high-lying Rydberg states and upshifting the continuum threshold, resulting in a suppression of three body recombination. Heating through collisionless absorption associated with the finite plasma size is calculated in detail, revealing a temperature threshold below which collisionless absorption is ineffective.Comment: 14 pages, 7 figure

Polarization-dependent ponderomotive gradient force in a standing wave

The ponderomotive force is derived for a relativistic charged particle entering an electromagnetic standing wave with a general three-dimensional field distribution and a nonrelativistic intensity, using a perturbation expansion method. It is shown that the well-known ponderomotive gradient force expression does not hold for this situation. The modified expression is still of simple gradient form, but contains additional polarization-dependent terms. These terms arise because the relativistic translational velocity induces a quiver motion in the direction of the magnetic force, which is the direction of large field gradients. Oscillation of the Lorentz factor effectively doubles this magnetic contribution. The derived ponderomotive force generalizes the polarization-dependent electron motion in a standing wave obtained earlier [A.E. Kaplan and A.L. Pokrovsky, Phys. Rev. Lett. $\bm{95}$, 053601 (2005)]. Comparison with simulations in the case of a realistic, non-idealized, three-dimensional field configuration confirms the general validity of the analytical results.Comment: 13 pages, 4 figure

Addition of 5-fluorouracil to doxorubicin-paclitaxel sequence increases caspase-dependent apoptosis in breast cancer cell lines

INTRODUCTION: The aim of the study was to evaluate the activity of a combination of doxorubicin (Dox), paclitaxel (Pacl) and 5-fluorouracil (5-FU), to define the most effective schedule, and to investigate the mechanisms of action in human breast cancer cells. METHODS: The study was performed on MCF-7 and BRC-230 cell lines. The cytotoxic activity was evaluated by sulphorhodamine B assay and the type of drug interaction was assessed by the median effect principle. Cell cycle perturbation and apoptosis were evaluated by flow cytometry, and apoptosis-related marker (p53, bcl-2, bax, p21), caspase and thymidylate synthase (TS) expression were assessed by western blot. RESULTS: 5-FU, used as a single agent, exerted a low cytotoxic activity in both cell lines. The Dox→Pacl sequence produced a synergistic cytocidal effect and enhanced the efficacy of subsequent exposure to 5-FU in both cell lines. Specifically, the Dox→Pacl sequence blocked cells in the G2-M phase, and the addition of 5-FU forced the cells to progress through the cell cycle or killed them. Furthermore, Dox→Pacl pretreatment produced a significant reduction in basal TS expression in both cell lines, probably favoring the increase in 5-FU activity. The sequence Dox→Pacl→48-h washout→5-FU produced a synergistic and highly schedule-dependent interaction (combination index < 1), resulting in an induction of apoptosis in both experimental models regardless of hormonal, p53, bcl-2 or bax status. Apoptosis in MCF-7 cells was induced through caspase-9 activation and anti-apoptosis-inducing factor hyperexpression. In the BRC-230 cell line, the apoptotic process was triggered only by a caspase-dependent mechanism. In particular, at the end of the three-drug treatment, caspase-8 activation triggered downstream executioner caspase-3 and, to a lesser degree, caspase-7. CONCLUSION: In our experimental models, characterized by different biomolecular profiles representing the different biology of human breast cancers, the schedule Dox→Pacl→48-h washout→5-FU was highly active and schedule-dependent and has recently been used to plan a phase I/II clinical protocol

Paclitaxel alters the expression and specific activity of deoxycytidine kinase and cytidine deaminase in non-small cell lung cancer cell lines

<p>Abstract</p> <p>Background</p> <p>We observed that paclitaxel altered the pharmacokinetic properties of gemcitabine in patients with non-small cell lung cancer (NSCLC) and limited the accumulation of gemcitabine and its metabolites in various primary and immortalized human cells. Therefore, we classified the drug-drug interaction and the effects of paclitaxel on deoxycytidine kinase (dCK) and cytidine deaminase (CDA) in three NSCLC cell lines. These enzymes are responsible for the metabolism of gemcitabine to its deaminated metabolite dFdU (80% of the parent drug) and the phosphorylated metabolites dFdCMP, dFdCDP and dFdCTP. These metabolites appear to relate to sensitivity and tolerability of gemcitabine based on previous animal and laboratory studies.</p> <p>Methods</p> <p>Three immortalized human cells representative of the most common histological subtypes identified in patients with advanced NSCLC were exposed to the individual drugs or combinations to complete a multiple drug effect analysis. These same cell lines were exposed to vehicle-control or paclitaxel and the mRNA levels, protein expression and specific activity of dCK and CDA were compared. Comparisons were made using a two-tailed paired t-test or analysis of variance with a P value of < 0.05 considered significant.</p> <p>Results</p> <p>The multiple drug effect analysis indicated synergy for H460, H520 and H838 cells independent of sequence. As anticipated, paclitaxel-gemcitabine increased the number of G2/M cells, whereas gemcitabine-paclitaxel increased the number of G0/G1 or S cells. Paclitaxel significantly decreased dCK and CDA mRNA levels in H460 and H520 cells (40% to 60%, P < 0.05) and lowered dCK protein (24% to 56%, P < 0.05) without affecting CDA protein. However, paclitaxel increased both dCK (10% to 50%) and CDA (75% to 153%) activity (P < 0.05). Paclitaxel caused substantial declines in the accumulation of the deaminated and phosphorylated metabolites in H520 cells (P < 0.05); the metabolites were not measurable in the remaining two cell lines. The ratio of dCK to CDA mRNA levels corresponded to the combination index (CI) estimated for sequential paclitaxel-gemcitabine.</p> <p>Conclusion</p> <p>In summary, paclitaxel altered the mRNA levels and specific activity of dCK and CDA and these effects could be dependent on histological subtype. More cell and animal studies are needed to further characterize the relationship between mRNA levels and the overall drug-drug interaction and the potential to use histological subtype as a predictive factor in the selection of an appropriate anticancer drug regimen.</p

Elevated risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variants compared with Alpha variant in vaccinated individuals

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) break through infection- or vaccine-induced immunity is not well understood. We analyzed 28,578 sequenced SARS-CoV-2 samples from individuals with known immune status obtained through national community testing in the Netherlands from March to August 2021. We found evidence of an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared with the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14 to 59 days after complete vaccination compared with ≥60 days. In contrast to vaccine-induced immunity, there was no increased risk for reinfection with Beta, Gamma, or Delta variants relative to the Alpha variant in individuals with infection-induced immunity.</p