Well-posedness, energy and charge conservation for nonlinear wave equations in discrete space-time

We consider the problem of discretization for the U(1)-invariant nonlinear wave equations in any dimension. We show that the classical finite-difference scheme used by Strauss and Vazquez \cite{MR0503140} conserves the positive-definite discrete analog of the energy if the grid ratio is $dt/dx\le 1/\sqrt{n}$, where $dt$ and $dx$ are the mesh sizes of the time and space variables and $n$ is the spatial dimension. We also show that if the grid ratio is $dt/dx=1/\sqrt{n}$, then there is the discrete analog of the charge which is conserved. We prove the existence and uniqueness of solutions to the discrete Cauchy problem. We use the energy conservation to obtain the a priori bounds for finite energy solutions, thus showing that the Strauss -- Vazquez finite-difference scheme for the nonlinear Klein-Gordon equation with positive nonlinear term in the Hamiltonian is conditionally stable.Comment: 10 page

Haploinsufficiency of microglial MyD88 ameliorates Alzheimer's pathology and vascular disorders in APP/PS1-transgenic mice

Growing evidence indicates that innate immune molecules regulate microglial activation in Alzheimer's disease (AD); however, their effects on amyloid pathology and neurodegeneration remain inconclusive. Here, we conditionally deleted one allele of myd88 gene specifically in microglia in APP/PS1-transgenic mice by 6 months and analyzed AD-associated pathologies by 9 months. We observed that heterozygous deletion of myd88 gene in microglia decreased cerebral amyloid β (Aβ) load and improved cognitive function of AD mice, which was correlated with reduced number of microglia in the brain and inhibited transcription of inflammatory genes, for example, tnf-α and il-1β, in both brain tissues and individual microglia. To investigate mechanisms underlying the pathological improvement, we observed that haploinsufficiency of MyD88 increased microglial recruitment toward Aβ deposits, which might facilitate Aβ clearance. Microglia with haploinsufficient expression of MyD88 also increased vasculature in the brain of APP/PS1-transgenic mice, which was associated with up-regulated transcription of osteopontin and insulin-like growth factor genes in microglia. Moreover, MyD88-haploinsufficient microglia elevated protein levels of LRP1 in cerebral capillaries of APP/PS1-transgenic mice. Cell culture experiments further showed that treatments with interleukin-1β decreased LRP1 expression in pericytes. In summary, haploinsufficiency of MyD88 in microglia at a late disease stage attenuates pro-inflammatory activation and amyloid pathology, prevents the impairment of microvasculature and perhaps also protects LRP1-mediated Aβ clearance in the brain of APP/PS1-transgenic mice, all of which improves neuronal function of AD mice

A Closed Contour of Integration in Regge Calculus

The analytic structure of the Regge action on a cone in $d$ dimensions over a boundary of arbitrary topology is determined in simplicial minisuperspace. The minisuperspace is defined by the assignment of a single internal edge length to all 1-simplices emanating from the cone vertex, and a single boundary edge length to all 1-simplices lying on the boundary. The Regge action is analyzed in the space of complex edge lengths, and it is shown that there are three finite branch points in this complex plane. A closed contour of integration encircling the branch points is shown to yield a convergent real wave function. This closed contour can be deformed to a steepest descent contour for all sizes of the bounding universe. In general, the contour yields an oscillating wave function for universes of size greater than a critical value which depends on the topology of the bounding universe. For values less than the critical value the wave function exhibits exponential behaviour. It is shown that the critical value is positive for spherical topology in arbitrary dimensions. In three dimensions we compute the critical value for a boundary universe of arbitrary genus, while in four and five dimensions we study examples of product manifolds and connected sums.Comment: 16 pages, Latex, To appear in Gen. Rel. Gra

Spallation Residues in the Reaction 56Fe + p at 0.3, 0.5, 0.75, 1.0 and 1.5 A GeV

The spallation residues produced in the bombardment of 56}Fe at 1.5, 1.0, 0.75, 0.5 and 0.3 A GeV on a liquid-hydrogen target have been measured using the reverse kinematics technique and the Fragment Separator at GSI (Darmstadt). This technique has permitted the full identification in charge and mass of all isotopes produced with cross-sections larger than 10^{-2} mb down to Z=8. Their individual production cross-sections and recoil velocities at the five energies are presented. Production cross-sections are compared to previously existing data and to empirical parametric formulas, often used in cosmic-ray astrophysics. The experimental data are also extensively compared to different combinations of intra-nuclear cascade and de-excitation models. It is shown that the yields of the lightest isotopes cannot be accounted for by standard evaporation models. The GEMINI model, which includes an asymmetric fission decay mode, gives an overall good agreement with the data. These experimental data can be directly used for the estimation of composition modifications and damages in materials containing iron in spallation sources. They are also useful for improving high precision cosmic-ray measurements.Comment: Submited to Phys. Rev. C (10/2006

Recoil Studies in the Reaction of 12-C Ions with the Enriched Isotope 118-Sn

The recoil properties of the product nuclei from the interaction of 2.2 GeV/nucleon 12-C ions from Nuclotron of the Laboratory of High Energies (LHE), Joint Institute for Nuclear Research (JINR) at Dubna with a 118-Sn target have been studied using catcher foils. The experimental data were analyzed using the mathematical formalism of the standard two-step vector model. The results for 12-C ions are compared with those for deuterons and protons. Three different Los Alamos versions of the Quark-Gluon String Model (LAQGSM) were used for comparison with our experimental data.Comment: 10 pages, 6 figures, submitted to Nucl. Phys.

Variation of nonequilibrium processes in p+Ni system with beam energy

The energy and angular dependence of double differential cross sections dsigma/dOmega dE were measured for p, d, t, 3,4He, 6,7Li, 7,9Be, and 10,11B produced in collisions of 0.175 GeV protons with Ni target. The analysis of measured dfferential cross sections allowed to extract total production cross sections for ejectiles listed above. The shape of the spectra and angular distributions indicate the presence of other nonequilibrium processes besides the emission of nucleons from the intranuclear cascade, and besides the evaporation of various particles from remnants of intranuclear cascade. These nonequilibrium processes consist of coalescence of nucleons into light charged particles during the intranuclear cascade, of the fireball emission which contributes to the cross sections of protons and deuterons, and of the break-up of the target nucleus which leads to the emission of intermediate mass fragments. All such processes were found earlier at beam energies 1.2, 1.9, and 2.5 GeV for Ni as well as for Au targets, however, significant differences in properties of these processes at high and low beam energy are observed in the present study.Comment: 10 pages, 9 figure

Competition of coalescence and "fireball" processes in nonequilibrium emission of light charged particles from p+Au collisions

The energy and angular dependence of double differential cross sections was measured for p,d,t,He,Li,Be, and B isotopes produced in collisions of 1.2 and 1.9 GeV protons with Au target. The shape of the spectra and angular distributions almost does not change in the beam energy range from 1.2 to 2.5 GeV, however, the absolute value of the cross sections increases for all ejectiles. A phenomenological model of two emitting, moving sources reproduces very well spectra and angular distributions of intermediate mass fragments. Double differential cross sections for light charged particles (LCP) were analyzed in the frame of the microscopic model of intranuclear cascade (INC) with coalescence of nucleons and statistical model for evaporation of particles from excited residual nuclei. Energy and angular dependencies of data agree satisfactorily neither with predictions of microscopic intranuclear cascade calculations for protons, nor with coalescence calculations for other LCP. Phenomenological inclusion of another reaction mechanism - emission of LCP from a "fireball", i.e., fast and hot moving source - combined with the microscopic model calculations of INC, coalescence and evaporation of particles leads to very good description of the data. It was found that nonequilibrium processes are very important for production of LCP. They exhaust 40-80% of the total cross sections - depending on the emitted particles. Coalescence and "fireball" emission give comparable contributions to the cross sections with exception of 3He data where coalescence clearly dominates. The ratio of sum of all nonequilibrium processes to those proceeding through stage of statistical equilibrium does almost not change in the beam energy range from 1.2 GeV to 2.5 GeV for all light charged particles.Comment: 14 pages, 12 figures, IV tables, \pacs{25.40.-h,25.40.Sc,25.40.Ve

A 115-bp MethyLight assay for detection of p16 (CDKN2A) methylation as a diagnostic biomarker in human tissues

<p>Abstract</p> <p>Background</p> <p><it>p16 </it>Methylation is a potential biomarker for prediction of malignant transformation of epithelial dysplasia. A probe-based, quantitative, methylation-specific PCR (MSP) called MethyLight may become an eligible method for detecting this marker clinically. We studied oral mucosa biopsies with epithelial dysplasia from 78 patients enrolled in a published 4-years' followup cohort, in which cancer risk for patients with <it>p16 </it>methylation-positive dysplasia was significantly higher than those without <it>p16 </it>methylation (by 150-bp MSP and bisulfite sequencing; +133 ~ +283, transcription starting site, +1). The <it>p16 </it>methylation status in samples (<it>N </it>= 102) containing sufficient DNA was analyzed by the 70-bp classic (+238 ~ +307) and 115-bp novel (+157 ~ +272) MethyLight assays, respectively.</p> <p>Results</p> <p><it>p16 </it>Methylation was detectable in 75 samples using the classic MethyLight assay. The methylated-<it>p16 </it>positive rate and proportion of methylated-<it>p16 </it>by the MethyLight in MSP-positive samples were higher than those in MSP-negative samples (positive rate: 37/44 vs. 38/58, <it>P</it>=0.035, two-sided; proportion [median]: 0.78 vs. 0.02, <it>P <</it>0.007). Using the published results of MSP as a golden standard, we found sensitivity, specificity, and accuracy for this MethyLight assay to be 70.5%, 84.5%, and 55.0%, respectively. Because amplicon of the classic MethyLight procedure only partially overlapped with the MSP amplicon, we further designed a 115-bp novel MethyLight assay in which the amplicon on the sense-strand fully overlapped with the MSP amplicon on the antisense-strand. Using the 115-bp MethyLight assay, we observed methylated-<it>p16 </it>in 26 of 44 MSP-positive samples and 2 of 58 MSP-negative ones (<it>P </it>= 0.000). These results were confirmed with clone sequencing. Sensitivity, specificity, and accuracy using the 115-bp MethyLight assay were 59.1%, 98.3%, and 57.4%, respectively. Significant differences in the oral cancer rate were observed during the followup between patients (≥60 years) with and without methylated-<it>p16 </it>as detected by the 115-bp MethyLight assay (6/8 vs. 6/22, P = 0.034, two-sided).</p> <p>Conclusions</p> <p>The 115-bp MethyLight assay is a useful and practical assay with very high specificity for the detection of <it>p16 </it>methylation clinically.</p

Spallation reactions. A successful interplay between modeling and applications

The spallation reactions are a type of nuclear reaction which occur in space by interaction of the cosmic rays with interstellar bodies. The first spallation reactions induced with an accelerator took place in 1947 at the Berkeley cyclotron (University of California) with 200 MeV deuterons and 400 MeV alpha beams. They highlighted the multiple emission of neutrons and charged particles and the production of a large number of residual nuclei far different from the target nuclei. The same year R. Serber describes the reaction in two steps: a first and fast one with high-energy particle emission leading to an excited remnant nucleus, and a second one, much slower, the de-excitation of the remnant. In 2010 IAEA organized a worskhop to present the results of the most widely used spallation codes within a benchmark of spallation models. If one of the goals was to understand the deficiencies, if any, in each code, one remarkable outcome points out the overall high-quality level of some models and so the great improvements achieved since Serber. Particle transport codes can then rely on such spallation models to treat the reactions between a light particle and an atomic nucleus with energies spanning from few tens of MeV up to some GeV. An overview of the spallation reactions modeling is presented in order to point out the incomparable contribution of models based on basic physics to numerous applications where such reactions occur. Validations or benchmarks, which are necessary steps in the improvement process, are also addressed, as well as the potential future domains of development. Spallation reactions modeling is a representative case of continuous studies aiming at understanding a reaction mechanism and which end up in a powerful tool.Comment: 59 pages, 54 figures, Revie

Tumor-infiltrating macrophages and dendritic cells in human colorectal cancer: relation to local regulatory T cells, systemic T-cell response against tumor-associated antigens and survival

<p>Abstract</p> <p>Introduction</p> <p>Although systemic T-cell responses against tumor antigens and tumor infiltration by T cells have been investigated in colorectal cancer (CRC), the initiation of spontaneous immune responses <it>in situ </it>is not well understood. Macrophages and dendritic cells (DC) play an important role as a link between innate and adaptive immune response. The aim of the present study was to analyze macrophage and DC infiltration in CRC and to investigate whether there is a correlation to systemic T-cell response, regulatory T cell (Treg) infiltration, and survival.</p> <p>Methods</p> <p>Immunohistological staining was performed with nine markers for macrophages and DC (CD68, CD163, S100, CD11c, CD208, CD209, CD123, CD1a, Langerin) in 40 colorectal cancer samples from patients, in whom the state of systemic T-cell responses against tumor-associated antigens (TAA) and Treg infiltration had previously been determined.</p> <p>Results</p> <p>All specimens contained cells positive for CD68, CD163, S100 and CD1a in epithelial tumor tissue and tumor stroma. Only a very few (less than median 3/HPF) CD123+, CD1a+, CD11c+, CD 208+, CD209+, or Langerin+ cells were detected in the specimens. Overall, we found a trend towards increased infiltration by S100-positive DC and a significantly increased number of stromal S100-positive DC in patients without T-cell response. There was an increase of stromal S100 DC and CD163 macrophages in limited disease (S100: 11.1/HPF vs. 7.3/HPF, p = 0.046; CD163: 11.0/HPF vs. 8.1/HPF, p = 0.06). We found a significant, positive correlation between S100-positive DC and FOXP3-positive Tregs. Survival in patients with high DC infiltration was significantly better than that in those with low DC infiltration (p < 0.05). Furthermore, we found a trend towards better survival for increased infiltration with CD163-positive macrophages (p = 0.07).</p> <p>Conclusion</p> <p>The present <it>in situ </it>study adds new data to the discussion on the interaction between the innate and adoptive immune system. Our data strongly support the hypothesis that tumor-infiltrating DC are a key factor at the interface between innate and adaptive immune response in malignant disease. Tumor infiltrating S100-positive DC show an inverse relationship with the systemic antigen-specific T-cell response, a positive correlation with regulatory T cells, and a positive association with survival in CRC. These data put tumor-infiltrating DC at the center of the relevant immune response in CRC.</p