848 research outputs found

    p21-activated kinase (PAK) regulates cytoskeletal reorganization and directional migration in human neutrophils

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    Neutrophils serve as a first line of defense in innate immunity owing in part to their ability to rapidly migrate towards chemotactic factors derived from invading pathogens. As a migratory function, neutrophil chemotaxis is regulated by the Rho family of small GTPases. However, the mechanisms by which Rho GTPases orchestrate cytoskeletal dynamics in migrating neutrophils remain ill-defined. In this study, we characterized the role of p21-activated kinase (PAK) downstream of Rho GTPases in cytoskeletal remodeling and chemotactic processes of human neutrophils. We found that PAK activation occurred upon stimulation of neutrophils with f-Met-Leu-Phe (fMLP), and PAK accumulated at the actin-rich leading edge of stimulated neutrophils, suggesting a role for PAK in Rac-dependent actin remodeling. Treatment with the pharmacological PAK inhibitor, PF3758309, abrogated the integrity of RhoA-mediated actomyosin contractility and surface adhesion. Moreover, inhibition of PAK activity impaired neutrophil morphological polarization and directional migration under a gradient of fMLP, and was associated with dysregulated Ca2+ signaling. These results suggest that PAK serves as an important effector of Rho-family GTPases in neutrophil cytoskeletal reorganization, and plays a key role in driving efficient directional migration of human neutrophils

    Delocalization in harmonic chains with long-range correlated random masses

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    We study the nature of collective excitations in harmonic chains with masses exhibiting long-range correlated disorder with power spectrum proportional to 1/kα1/k^{\alpha}, where kk is the wave-vector of the modulations on the random masses landscape. Using a transfer matrix method and exact diagonalization, we compute the localization length and participation ratio of eigenmodes within the band of allowed energies. We find extended vibrational modes in the low-energy region for α>1\alpha > 1. In order to study the time evolution of an initially localized energy input, we calculate the second moment M2(t)M_2(t) of the energy spatial distribution. We show that M2(t)M_2(t), besides being dependent of the specific initial excitation and exhibiting an anomalous diffusion for weakly correlated disorder, assumes a ballistic spread in the regime α>1\alpha>1 due to the presence of extended vibrational modes.Comment: 6 pages, 9 figure

    An attempt to understand exclusive pi+ electroproduction

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    Hard exclusive pi+ electroproduction is investigated within the handbag approach. The prominent role of the pion-pole contribution is demonstrated. It is also shown that the experimental data require a twist-3 effect which ensues from the helicity-flip generalized parton distribution H_T and the twist-3 pion wave function. The results calculated from this handbag approach are compared in detail with the experimental data on cross sections and spin asymmetries measured with a polarized target. It is also commented on consequences of this approach for exclusive \pi^0 and vector-meson electroproduction.Comment: 35 pages, 12 figures, using Latex, a number of additional comments have been included in the text, e.g. in paragraph above (3) or at end of sect.

    Breaking the low-pay, no-pay cycle: Final evidence from the UK Employment Retention and Advancement (ERA) demonstration

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    This report presents the final results on the implementation, impacts, costs, and economic benefits of the UK Employment Retention and Advancement (ERA) programme. ERA’s distinctive combination of post-employment advisory support and financial incentives was designed to help low-income individuals who entered work sustain employment and advance in the labour market. Launched in 2003 in selected Jobcentre Plus offices, ERA targeted three groups: (1) unemployed lone parents receiving Income Support and volunteering for the New Deal for Lone Parents welfare-to-work programme, (2) lone parents working part time and receiving Working Tax Credit, and (3) long-term unemployed people aged 25 or older receiving Jobseeker’s Allowance who were required to participate in the New Deal 25 Plus welfare-to-work programme. The effectiveness of the programme was evaluated using a random assignment research design. The evaluation found that ERA produced short-term earnings gains for the two lone parent target groups. The early gains resulted from increases in the proportion of participants who worked full time (at least 30 hours per week). However, these effects generally faded after the programme ended, largely because the control group caught up with the ERA group. More impressive were the results for the long-term unemployed participants (mostly men) in the New Deal 25 Plus target group. For them, ERA produced modest but sustained increases in employment and substantial and sustained increases in earnings. These positive effects emerged after the first year and were still evident at the end of a five-year follow-up period. The earnings gains were accompanied by lasting reductions in benefits receipt. ERA proved cost-effective for this group from the perspectives of the participants themselves, the Government budget, and society as a whole

    Strangeness nuclear physics: a critical review on selected topics

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    Selected topics in strangeness nuclear physics are critically reviewed. This includes production, structure and weak decay of Λ\Lambda--Hypernuclei, the Kˉ\bar K nuclear interaction and the possible existence of Kˉ\bar K bound states in nuclei. Perspectives for future studies on these issues are also outlined.Comment: 63 pages, 51 figures, accepted for publication on European Physical Journal

    MD simulations of He evaporating from dodecane

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    The velocity distribution of He atoms evaporating from a slab of liquid dodecane has been simulated. The distribution composed of ∼10 000 He trajectories is shifted to fractionally faster velocities as compared to a Maxwell–Boltzmann distribution at the temperature of the liquid dodecane with an average translational energy of 1.05 × 2RT (or 1.08 × 2RT after correction for a cylindrical liquid jet), compared to the experimental work by Nathanson and co-workers (1.14 × 2RT) on liquid jets. Analysis of the trajectories allows us to infer mechanistic information about the modes of evaporation, and their contribution to the overall velocity distribution
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