Azimuthal Correlations in the Target Fragmentation Region of High Energy Nuclear Collisions

Results on the target mass dependence of proton and pion pseudorapidity distributions and of their azimuthal correlations in the target rapidity range $-1.73 \le \eta \le 1.32$ are presented. The data have been taken with the Plastic-Ball detector set-up for 4.9 GeV p + Au collisions at the Berkeley BEVALAC and for 200 $A\cdot$GeV/$c$ p-, O-, and S-induced reactions on different nuclei at the CERN-SPS. The yield of protons at backward rapidities is found to be proportional to the target mass. Although protons show a typical ``back-to-back'' correlations, a ``side-by-side'' correlation is observed for positive pions, which increases both with target mass and with impact parameter of a collision. The data can consistently be described by assuming strong rescattering phenomena including pion absorption effects in the entire excited target nucleus.Comment: 7 pages, figures included, complete postscript available at ftp://qgp.uni-muenster.de/pub/paper/azi-correlations.ps submitted to Phys. Lett.

Event-by-Event Fluctuations in Particle Multiplicities and Transverse Energy Produced in 158.A GeV Pb+Pb collisions

Event-by-event fluctuations in the multiplicities of charged particles and photons, and the total transverse energy in 158$\cdot A$ GeV Pb+Pb collisions are studied for a wide range of centralities. For narrow centrality bins the multiplicity and transverse energy distributions are found to be near perfect Gaussians. The effect of detector acceptance on the multiplicity fluctuations has been studied and demonstrated to follow statistical considerations. The centrality dependence of the charged particle multiplicity fluctuations in the measured data has been found to agree reasonably well with those obtained from a participant model. However for photons the multiplicity fluctuations has been found to be lower compared to those obtained from a participant model. The multiplicity and transverse energy fluctuations have also been compared to those obtained from the VENUS event generator.Comment: To appear in Physical Review C; changes : more detailed discussion on errors and few figures modifie

Pion Freeze-Out Time in Pb+Pb Collisions at 158 A GeV/c Studied via pi-/pi+ and K-/K+ Ratios

The effect of the final state Coulomb interaction on particles produced in Pb+Pb collisions at 158 A GeV/c has been investigated in the WA98 experiment through the study of the pi-/pi+ and K-/K+ ratios measured as a function of transverse mass. While the ratio for kaons shows no significant transverse mass dependence, the pi-/pi+ ratio is enhanced at small transverse mass values with an enhancement that increases with centrality. A silicon pad detector located near the target is used to estimate the contribution of hyperon decays to the pi-/pi+ ratio. The comparison of results with predictions of the RQMD model in which the Coulomb interaction has been incorporated allows to place constraints on the time of the pion freeze-out.Comment: 9 pages, 12 figure

Centrality Dependence of Neutral Pion Production in 158 A GeV Pb + Pb Collisions

The production of neutral pions in 158AGeV Pb+Pb collisions has been studied in the WA98 experiment at the CERN SPS. Transverse momentum spectra are studied for the range 0.3 GeV/c < mT-m0 < 4.0 GeV/c. The results for central collisions are compared to various models. The centrality dependence of the neutral pion spectral shape and yield is investigated. An invariance of the spectral shape and a simple scaling of the yield with the number of participating nucleons is observed for centralities with greater than about 30 participating nucleons which is most naturally explained by assuming an equilibrated system.Comment: 5 pages, Latex, including 3 eps figures, submitted to Phys.Rev.Lett; updated pQCD comparison due to new input from the author, updated references, corrected plotting error in figure

Multiplicity Distributions and Charged-neutral Fluctuations

Results from the multiplicity distributions of inclusive photons and charged particles, scaling of particle multiplicities, event-by-event multiplicity fluctuations, and charged-neutral fluctuations in 158$\cdot A$ GeV Pb+Pb collisions are presented and discussed. A scaling of charged particle multiplicity as $N_{part}^{1.07\pm 0.05}$ and photons as $N_{part}^{1.12\pm 0.03}$ have been observed, indicating violation of naive wounded nucleon model. The analysis of localized charged-neutral fluctuation indicates a model-independent demonstration of non-statistical fluctuations in both charged particles and photons in limited azimuthal regions. However, no correlated charged-neutral fluctuations are observed.Comment: Talk given at the International Symposium on Nuclear Physics (ISNP-2000), Mumbai, India, 18-22 Dec 2000, Proceedings to be published in Pramana, Journal of Physic

A DNA Spiegelmer to staphylococcal enterotoxin B

Bacterial staphylococcal enterotoxin B is involved in several severe disease patterns and it was therefore used as a target for the generation of biologically stable mirror-image oligonucleotide ligands, so called Spiegelmers. The toxin is a 28 kDa protein consisting of 239 amino acids. Since the full-length protein is not accessible to chemical peptide synthesis, a stable domain of 25 amino acids was identified as a suitable selection target. DNA in vitro selection experiments were carried out against the equivalent mirror-image d-peptide domain resulting in high affinity d-DNA aptamers. As expected, the corresponding enantiomeric l-DNA Spiegelmer showed comparable binding characteristics to the l-peptide domain. Moreover, the Spiegelmer bound the whole protein target with only slightly reduced affinity. Dissociation constants of both peptide–oligonucleotide complexes were measured in the range of 200 nM, whereas the Spiegelmer binding to the full-length protein was determined at ∼420 nM. These data demonstrate the possibility to identify Spiegelmers against large protein targets by a domain approach

The effects of the anti-hepcidin Spiegelmer NOX-H94 on inflammation-induced anemia in cynomolgus monkeys

Item does not contain fulltextAnemia of chronic inflammation is the most prevalent form of anemia in hospitalized patients. A hallmark of this disease is the intracellular sequestration of iron. This is a consequence of hepcidin-induced internalization and subsequent degradation of ferroportin, the hepcidin receptor and only known iron-export protein. This study describes the characterization of novel anti-hepcidin compound NOX-H94, a structured L-oligoribonucleotide that binds human hepcidin with high affinity (Kd = 0.65 +/- 0.06 nmol/L). In J774A.1 macrophages, NOX-H94 blocked hepcidin-induced ferroportin degradation and ferritin expression (half maximal inhibitory concentration = 19.8 +/- 4.6 nmol/L). In an acute cynomolgus monkey model of interleukin 6 (IL-6)-induced hypoferremia, NOX-H94 inhibited serum iron reduction completely. In a subchronic model of IL-6-induced anemia, NOX-H94 inhibited the decrease in hemoglobin concentration. We conclude that NOX-H94 protects ferroportin from hepcidin-induced degradation. Therefore, this pharmacologic approach may represent an interesting treatment option for patients suffering from anemia of chronic inflammation

SDF-1 Inhibition Targets the Bone Marrow Niche for Cancer Therapy

Summary: Bone marrow (BM) metastasis remains one of the main causes of death associated with solid tumors as well as multiple myeloma (MM). Targeting the BM niche to prevent or modulate metastasis has not been successful to date. Here, we show that stromal cell-derived factor-1 (SDF-1/CXCL12) is highly expressed in active MM, as well as in BM sites of tumor metastasis and report on the discovery of the high-affinity anti-SDF-1 PEGylated mirror-image l-oligonucleotide (olaptesed-pegol). In vivo confocal imaging showed that SDF-1 levels are increased within MM cell-colonized BM areas. Using in vivo murine and xenograft mouse models, we document that in vivo SDF-1 neutralization within BM niches leads to a microenvironment that is less receptive for MM cells and reduces MM cell homing and growth, thereby inhibiting MM disease progression. Targeting of SDF-1 represents a valid strategy for preventing or disrupting colonization of the BM by MM cells. : Roccaro et al. show that stromal-cell-derived factor-1 (SDF-1) is highly expressed in active multiple myeloma (MM), as well as in bone marrow (BM) sites of tumor metastasis, and report on a high-affinity PEGylated mirror-image l-oligonucleotide (olaptesed pegol) that specifically binds and neutralizes SDF-1 in vitro and in vivo. Using in vivo murine and xenograft mouse models, the authors document that in vivo SDF-1 neutralization within BM niches leads to a microenvironment that is less receptive for MM cells and reduces clonal plasma cell homing and growth, thereby inhibiting MM disease progression