On the many-time formulation of classical particle dynamics

Starting from the standard one-time dynamics of n nonrelativistic particles, the n-time equations of motion are inferred, and a variational principle is formulated. A suitable generalization of the classical LieKnig theorem is demonstrated, which allows the determination of all the associated presymplectic structures. The conditions under which the action of an invariance group is canonical are studied, and a corresponding Noether theorem is deduced. A formulation of the theory in terms of n first-class constraints is recovered by means of coisotropic imbeddings. The proposed approach also provides for a better understanding of the relativistic particle dynamics, since it shows that the different roles of the physical positions and the canonical variables is not peculiar to special relativity, but rather to any n-time approach: indeed a nonrelativistic no-interaction theorem is deduced.

Charged-particle interaction with liquids: Ripplon excitations

We calculate the ripplon field contribution to the self-energy of an electron exterior to a liquid for planar and spherical geometries. We compare the full dielectric calculation of the electron-liquid interaction with the simpler alternative method consisting of integrating the electron-atom static-induced-dipolar potential through the whole liquid volume. We obtain good agreement between both methods for a nonpolar liquid such as 4He but differences up to 40% for a polar liquid such as water. We study the conditions under which the ripplon contribution to the self-energy is a perturbation. For an electron moving parallel to a planar liquid surface, we calculate the ripplon contribution to its stopping power. For this dynamical case, we conclude that the alternative method is a good approximation even for polar liquids.

Building predictive models of soil particle-size distribution

Is it possible to build predictive models (PMs) of soil particle-size distribution (psd) in a region with complex geology and a young and unstable land-surface? The main objective of this study was to answer this question. A set of 339 soil samples from a small slope catchment in Southern Brazil was used to build PMs of psd in the surface soil layer. Multiple linear regression models were constructed using terrain attributes (elevation, slope, catchment area, convergence index, and topographic wetness index). The PMs explained more than half of the data variance. This performance is similar to (or even better than) that of the conventional soil mapping approach. For some size fractions, the PM performance can reach 70 %. Largest uncertainties were observed in geologically more complex areas. Therefore, significant improvements in the predictions can only be achieved if accurate geological data is made available. Meanwhile, PMs built on terrain attributes are efficient in predicting the particle-size distribution (psd) of soils in regions of complex geology.

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine.

Background. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. Methods. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination. Results. We showed that YF-17D-induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D-neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination. Conclusion. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity. Trial registration. Registration is not required for observational studies. Funding. This study was funded by Canada's Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United States Agency for International Development.

Particle agglomeration study in rf silane plasmas: In situ study by polarization-sensitive laser light scattering

To determine self‐consistently the time evolution of particle size and their number density in situ multi‐angle polarization‐sensitive laser light scattering was used. Cross‐polarization intensities (incident and scattered light intensities with opposite polarization) measured at 135° and ex situ transmission electronic microscopy analysis demonstrate the existence of nonspherical agglomerates during the early phase of agglomeration. Later in the particle time development both techniques reveal spherical particles again. The presence of strong cross‐polarization intensities is accompanied by low‐frequency instabilities detected on the scattered light intensities and plasma emission. It is found that the particle radius and particle number density during the agglomeration phase can be well described by the Brownian free molecule coagulation model. Application of this neutral particle coagulation model is justified by calculation of the particle charge whereby it is shown that particles of a few tens of nanometer can be considered as neutral under our experimental conditions. The measured particle dispersion can be well described by a Brownian free molecule coagulation model including a log‐normal particle size distribution.

Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors.

Tumor progression is facilitated by regulatory T cells (Treg) and restricted by effector T cells. In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1). In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4. Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines. Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice. Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression. Cancer Res; 73(12); 3591-603. ©2013 AACR.

New constraints on a light spinless particle coupled to photons

We obtain new stringent constraints on a light spinless particle f coupled only to photons at low energies, considering its effects on the extragalactic photon background, the black-body spectrum of the cosmic microwave background radiation and the cosmological abundance of deuterium.

Motion of a classical charged particle

The Lorentz-Dirac equation is not an unavoidable consequence of solely linear and angular momenta conservation for a point charge. It also requires an additional assumption concerning the elementary character of the charge. We here use a less restrictive elementarity assumption for a spinless charge and derive a system of conservation equations that are not properly the equation of motion because, as it contains an extra scalar variable, the future evolution of the charge is not determined. We show that a supplementary constitutive relation can be added so that the motion is determined and free from the troubles that are customary in the Lorentz-Dirac equation, i.e., preacceleration and runaways.

Particle and string fluid interpretation for the scalar sector of Kaluza-Klein theories

The scalar sector of the effective low-energy six-dimensional Kaluza-Klein theory is seen to represent an anisotropic fluid composed of two perfect fluids if the extra space metric has a Euclidean signature, or a perfect fluid of geometric strings if it has an indefinite signature. The Einstein field equations with such fluids can be explicitly integrated when the four-dimensional space-time has two commuting Killing vectors.

Particle creation due to cosmological contraction of extra dimensions

Particle production in a cosmological spacetime with extra dimensions is discussed. A five-dimensional cosmological model with a three-dimensional space expanding isotropically like in a radiative Friedmann-Robertson-Walker model and an internal space contracting to a constant small size is considered. The parameters of the model are adjusted so that time variations in internal space are compatible with present limits on time variations of the fundamental constants. By requiring that the energy density of the particles produced be less than the critical density at the radiation era we set restrictions on two more parameters: namely, the initial time of application of the semiclassical approach and the relative sizes between the internal space and the horizon of the ordinary Universe at this time. Whereas the production of massless particles allows a large range of variation to these parameters, the production of massive particles sets severe constraints on them, since, if they are overproduced, their energy density might very soon dominate the Universe and make cosmological dimensional reduction by extradimensional contraction unlikely.

Particle creation in a colliding plane wave spacetime: Wave packet quantization

We use wave packet mode quantization to compute the creation of massless scalar quantum particles in a colliding plane wave spacetime. The background spacetime represents the collision of two gravitational shock waves followed by trailing gravitational radiation which focus into a Killing-Cauchy horizon. The use of wave packet modes simplifies the problem of mode propagation through the different spacetime regions which was previously studied with the use of monochromatic modes. It is found that the number of particles created in a given wave packet mode has a thermal spectrum with a temperature which is inversely proportional to the focusing time of the plane waves and which depends on the mode trajectory.

PAR2 Promotes Vaccine-Induced Protection Against Helicobacter Infection in Mice.

BACKGROUND & AIMS: Protective immunization limits Helicobacter infection of mice by undetermined mechanisms. Protease-activated receptor 2 (PAR2) signaling is believed to regulate immune and inflammatory responses. We investigated the role of PAR2 in vaccine-induced immunity against Helicobacter infection. METHODS: Immune responses against Helicobacter infection were compared between vaccinated PAR2(-/-) and wild-type (WT) mice. Bacterial persistence, gastric pathology, and inflammatory and cellular responses were assessed using the rapid urease test (RUT), histologic analyses, quantitative polymerase chain reaction, and flow cytometry, respectively. RESULTS: Following vaccination, PAR2(-/-) mice did not have reductions in Helicobacter felis infection (RUT values were 0.01 ± 0.01 for WT mice and 0.11 ± 0.13 for PAR2(-/-) mice; P < .05). The vaccinated PAR2(-/-) mice had reduced inflammation-induced stomach tissue damage (tissue damage scores were 8.83 ± 1.47 for WT mice and 4.86 ± 1.35 for PAR2(-/-) mice; P < .002) and reduced T-helper (Th)17 responses, based on reduced urease-induced interleukin (IL)-17 secretion by stomach mononuclear cells (5182 ± 1265 pg/mL for WT mice and 350 ± 436 pg/mL for PAR2(-/-) mice; P < .03) and reduced recruitment of CD4(+) IL-17(+) T cells into the gastric mucosa of PAR2(-/-) mice following bacterial challenge (3.7% ± 1.5% for WT mice and 2.6% ± 1.1% for PAR2(-/-) mice; P < .05). In vitro, H felis-stimulated dendritic cells (DCs) from WT mice induced greater secretion of IL-17 by ovalbumin-stimulated OT-II transgenic CD4(+) T cells compared with DCs from PAR2(-/-) mice (4298 ± 347 and 3230 ± 779; P < .04), indicating that PAR2(-/-) DCs are impaired in priming of Th17 cells. Adoptive transfer of PAR2(+/+) DCs into vaccinated PAR2(-/-) mice increased vaccine-induced protection (RUT values were 0.11 ± 0.10 and 0.26 ± 0.15 for injected and noninjected mice, respectively; P < .03). CONCLUSIONS: PAR2 activates DCs to mediate vaccine-induced protection against Helicobacter infection in mice.

Onsager symmetry principle for a particle moving through a fluid not in equilibrium

We have shown that the mobility tensor for a particle moving through an arbitrary homogeneous stationary flow satisfies generalized Onsager symmetry relations in which the time-reversal transformation should also be applied to the external forces that keep the system in the stationary state. It is then found that the lift forces, responsible for the motion of the particle in a direction perpendicular to its velocity, have different parity than the drag forces.