Empirical description of the hadron-hadron and hadron-nucleus interaction at the accelerator energy range

Taking into account several assumptions, a formula is transformed into two expressions for kaon and baryon plus antibaryon production in proton interaction and for pion production in pion interactions. Combining both formulae, expression are obtained for the spectrum of kaons and baryons plus antibaryons produced in the meson interactions. For analysis of the cosmic ray propagation in the atmosphere in actual fact, instead of the formulae for interactions of protons and mesons with protons, formulae appropriate for interactions with air nuclei was used. Using the method outlined among others by Elias et al. (1980) simple corrections were introduced to the derived expressions to account for the fact that the target is an air nucleus

Physical interaction between MYCN oncogene and polycomb repressive complex 2 (PRC2) in neuroblastoma: Functional and therapeutic implications

This article is made available through the Brunel Open Access Publishing Fund. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.CLU (clusterin) is a tumor suppressor gene that we have previously shown to be negatively modulated by the MYCN proto-oncogene, but the mechanism of repression was unclear. Here, we show that MYCN inhibits the expression of CLU by direct interaction with the non-canonical E box sequence CACGCG in the 5′-flanking region. Binding of MYCN to the CLU gene induces bivalent epigenetic marks and recruitment of repressive proteins such as histone deacetylases and Polycomb members. MYCN physically binds in vitro and in vivo to EZH2, a component of the Polycomb repressive complex 2, required to repress CLU. Notably, EZH2 interacts with the Myc box domain 3, a segment of MYC known to be essential for its transforming effects. The expression of CLU can be restored in MYCN-amplified cells by epigenetic drugs with therapeutic results. Importantly, the anticancer effects of the drugs are ablated if CLU expression is blunted by RNA interference. Our study implies that MYC tumorigenesis can be effectively antagonized by epigenetic drugs that interfere with the recruitment of chromatin modifiers at repressive E boxes of tumor suppressor genes such as CLU.SPARKS, The Neuroblastoma Society, a Wellcome Trust grant (to A. S.), and the Italian Association for Cancer Research

Stretching magnetism with an electric field in a nitride semiconductor

By direct magnetization measurements, performed employing a new detection scheme, we demonstrate an electrical control of magnetization in wurtzite (Ga,Mn)N. In this dilute magnetic insulator the Fermi energy is pinned by Mn ions in the mid-gap region, and the Mn3+ ions show strong single-ion anisotropy. We establish that (Ga,Mn)N sustains an electric field up to at least 5 MV/cm, indicating that Mn doping turns GaN into a worthwhile semi-insulating material. Under these conditions, the magnetoelectric coupling may be driven by the inverse piezoelectric effect that stretches the elementary cell along the c axis and, thus, affects the magnitude of magnetic anisotropy. We develop a corresponding theory and show that it describes the experimentally determined dependence of magnetization on the electric field quantitatively with no adjustable parameters as a function of the magnetic field and temperature. In this way, our work bridges two research domains developed so far independently: piezoelectricity of wurtzite semiconductors and electrical control of magnetization in hybrid and composite magnetic structures containing piezoelectric components.Comment: 11 pages, 10 figures, version after revisio

Polyphenon E enhances the antitumor immune response in neuroblastoma by inactivating myeloid suppressor cells

This is the author's accepted manuscript. The final published article is available from the link below. Note: In this manuscript as well as in the original published version of this article the word "Polyphenon" was incorrectly spelled in the title as "Polyphenol."Purpose: Neuroblastoma is a rare childhood cancer whose high risk, metastatic form has a dismal outcome in spite of aggressive therapeutic interventions. The toxicity of drug treatments is a major problem in this pediatric setting. In this study, we investigated whether Polyphenon E, a clinical grade mixture of green tea catechins under evaluation in multiple clinical cancer trials run by the National Cancer Institute (Bethesda, MD), has anticancer activity in mouse models of neuroblastoma. Experimental Design: We used three neuroblastoma models: (i) transgenic TH-MYCN mouse developing spontaneous neuroblastomas; (ii) nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice xenotransplanted with human SHSY5Y cells; and (iii) A/J mice transplanted with syngeneic Neuro 2A cells. Mice were randomized in control and Polyphenon E–drinking groups. Blood from patients with neuroblastoma and normal controls was used to assess the phenotype and function of myeloid cells. Results: Polyphenon E reduced the number of tumor-infiltrating myeloid cells, and inhibited the development of spontaneous neuroblastomas in TH-MYCN transgenic mice. In therapeutic models of neuroblastoma in A/J, but not in immunodeficient NOD/SCID mice, Polyphenon E inhibited tumor growth by acting on myeloid-derived suppressor cells (MDSC) and CD8 T cells. In vitro, Polyphenon E impaired the development and motility of MDSCs and promoted differentiation to more neutrophilic forms through the 67 kDa laminin receptor signaling and induction of granulocyte colony-stimulating factor. The proliferation of T cells infiltrating a patient metastasis was reactivated by Polyphenon E. Conclusions: These findings suggest that the neuroblastoma-promoting activity of MDSCs can be manipulated pharmacologically in vivo and that green tea catechins operate, at least in part, through this mechanism.SPARKS, Research in Childhood Cancer, the CGD Research Trust, and the Wellcome Trust

Blastomeres arising from the first cleavage division have distinguishable fates in normal mouse development

Two independent studies have recently suggested similar models in which the embryonic and abembryonic parts of the mouse blastocyst become separated already by the first cleavage division. However, no lineage tracing studies carried out so far on early embryos provide the support for such a hypothesis. Thus, to re-examine the fate of blastomeres of the two-cell mouse embryo, we have undertaken lineage tracing studies using a non-perturbing method. We show that two-cell stage blastomeres have a strong tendency to develop into cells that comprise either the embryonic or the abembryonic parts of the blastocyst. Moreover, the two-cell stage blastomere that is first to divide will preferentially contribute its progeny to the embryonic part. Nevertheless, we find that the blastocyst embryonic-abembryonic axis is not perfectly orthogonal to the first cleavage plane, but often shows some angular displacement from it. Consequently, there is a boundary zone adjacent to the interior margin of the blastocoel that is populated by cells derived from both earlier and later dividing blastomeres. The majority of cells that inhabit this boundary region are, however, derived from the later dividing two-cell stage blastomere that contributes predominantly to the abembryonic part of the blastocyst. Thus, at the two-cell stage it is already possible to predict which cell will contribute a greater proportion of its progeny to the abembryonic part of the blastocyst (region including the blastocyst cavity) and which to the embryonic part (region containing the inner cell mass) that will give rise to the embryo proper

Simulating the Mammalian Blastocyst - Molecular and Mechanical Interactions Pattern the Embryo

Mammalian embryogenesis is a dynamic process involving gene expression and mechanical forces between proliferating cells. The exact nature of these interactions, which determine the lineage patterning of the trophectoderm and endoderm tissues occurring in a highly regulated manner at precise periods during the embryonic development, is an area of debate. We have developed a computational modeling framework for studying this process, by which the combined effects of mechanical and genetic interactions are analyzed within the context of proliferating cells. At a purely mechanical level, we demonstrate that the perpendicular alignment of the animal-vegetal (a-v) and embryonic-abembryonic (eb-ab) axes is a result of minimizing the total elastic conformational energy of the entire collection of cells, which are constrained by the zona pellucida. The coupling of gene expression with the mechanics of cell movement is important for formation of both the trophectoderm and the endoderm. In studying the formation of the trophectoderm, we contrast and compare quantitatively two hypotheses: (1) The position determines gene expression, and (2) the gene expression determines the position. Our model, which couples gene expression with mechanics, suggests that differential adhesion between different cell types is a critical determinant in the robust endoderm formation. In addition to differential adhesion, two different testable hypotheses emerge when considering endoderm formation: (1) A directional force acts on certain cells and moves them into forming the endoderm layer, which separates the blastocoel and the cells of the inner cell mass (ICM). In this case the blastocoel simply acts as a static boundary. (2) The blastocoel dynamically applies pressure upon the cells in contact with it, such that cell segregation in the presence of differential adhesion leads to the endoderm formation. To our knowledge, this is the first attempt to combine cell-based spatial mechanical simulations with genetic networks to explain mammalian embryogenesis. Such a framework provides the means to test hypotheses in a controlled in silico environment

Disorder suppression and precise conductance quantization in constrictions of PbTe quantum wells

Conductance quantization was measured in submicron constrictions of PbTe, patterned into narrow,12 nm wide quantum wells deposited between Pb$_{0.92}$Eu$_{0.08}$Te barriers. Because the quantum confinement imposed by the barriers is much stronger than the lateral one, the one-dimensional electron energy level structure is very similar to that usually met in constrictions of AlGaAs/GaAs heterostructures. However, in contrast to any other system studied so far, we observe precise conductance quantization in $2e^2/h$ units, {\it despite of significant amount of charged defects in the vicinity of the constriction}. We show that such extraordinary results is a consequence of the paraelectric properties of PbTe, namely, the suppression of long-range tails of the Coulomb potentials due to the huge dielectric constant.Comment: 7 pages, 6 figures, submitted to Phys. Rev.

Emissions from pre-Hispanic metallurgy in the South American atmosphere

This is the final version of the article. Available from Public Library of Science via the DOI in this record.Metallurgical activities have been undertaken in northern South America (NSA) for millennia. However, it is still unknown how far atmospheric emissions from these activities have been transported. Since the timing of metallurgical activities is currently estimated from scarce archaeological discoveries, the availability of reliable and continuous records to refine the timing of past metal deposition in South America is essential, as it provides an alternative to discontinuous archives, as well as evidence for global trace metal transport. We show in a peat record from Tierra del Fuego that anthropogenic metals likely have been emitted into the atmosphere and transported from NSA to southern South America (SSA) over the last 4200 yrs. These findings are supported by modern time back-trajectories from NSA to SSA. We further show that apparent anthropogenic Cu and Sb emissions predate any archaeological evidence for metallurgical activities. Lead and Sn were also emitted into the atmosphere as by-products of Inca and Spanish metallurgy, whereas local coal-gold rushes and the industrial revolution contributed to local contamination. We suggest that the onset of pre-Hispanic metallurgical activities is earlier than previously reported from archaeological records and that atmospheric emissions of metals were transported from NSA to SSA.This research is supported by a Young Researcher Grant of the Agence Nationale de la Recherche (ANR) to F. De Vleeschouwer (Project ANR-2011-JS56-006-01 “PARAD”). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript