Kaon and Φ\Phi production vs Participants in Nuclear Collisions

Data on kaon and $\Phi$ production in nuclear collisions as a function of centrality are analysed both at AGS and SPS energy range. We compare the results of several experiments, looking for common trend in `participant scaling' of production yields. We find a smooth description of scaled kaon and $\Phi$ yields as a function of participant density. We also show a participant density dependence of kaons and $\Phi$ produced in the forward hemisphere for proton-nucleus collisions.Comment: Proceedings of the International Conference on Strangeness in Quark Matter, 20-25 July 2000, Berkeley, CA. To appear in Journal of Physics G: Nuclear and Particle Physic

Reply to Comment of Gazdzicki and Heinz on Strangeness Enhancement in p+Ap+A and S+AS+A

The Comment of Gazdzicki and Heinz is flawed because their assumed baryon stopping power in $pA$ is inconsistent with data and because they ignored half the analysis based on the VENUS model. The Comment continues the misleading presentation of strangeness enhancement by focusing on ratios of integrated yields. Those ratios discard essential experimental information on the rapidity dependence of produced $\Lambda$ and obscure discrepancies between different data sets. Our conclusion remains that the NA35 minimum bias data on $p+S\rightarrow\Lambda +X$ indicate an anomalous enhancement of central rapidity strangeness in few nucleon reactions that points to non-equilibrium dynamics as responsible for strangeness enhancement in nuclear reactions.Comment: revtex file, 6 pages, submitted to Phys. Rev.

Cell-specific targeting of lentiviral vectors mediated by fusion proteins derived from Sindbis virus, vesicular stomatitis virus, or avian sarcoma/leukosis virus

<p>Abstract</p> <p>Background</p> <p>The ability to efficiently and selectively target gene delivery vectors to specific cell types <it>in vitro </it>and <it>in vivo </it>remains one of the formidable challenges in gene therapy. We pursued two different strategies to target lentiviral vector delivery to specific cell types. In one of the strategies, vector particles bearing a membrane-bound stem cell factor sequence plus a separate fusion protein based either on Sindbis virus strain TR339 glycoproteins or the vesicular stomatitis virus G glycoprotein were used to selectively transduce cells expressing the corresponding stem cell factor receptor (c-kit). An alternative approach involved soluble avian sarcoma/leukosis virus receptors fused to cell-specific ligands including stem cell factor and erythropoietin for targeting lentiviral vectors pseudotyped with avian sarcoma/leukosis virus envelope proteins to cells that express the corresponding receptors.</p> <p>Results</p> <p>The titers of unconcentrated vector particles bearing Sindbis virus strain TR339 or vesicular stomatitis virus G fusion proteins plus stem cell factor in the context of c-kit expressing cells were up to 3.2 × 10⁵transducing units per ml while vector particles lacking the stem cell factor ligand displayed titers that were approximately 80 fold lower. On cells that lacked the c-kit receptor, the titers of stem cell factor-containing vectors were approximately 40 times lower compared to c-kit-expressing cells.</p> <p>Lentiviral vectors pseudotyped with avian sarcoma/leukosis virus subgroup A or B envelope proteins and bearing bi-functional bridge proteins encoding erythropoietin or stem cell factor fused to the soluble extracellular domains of the avian sarcoma/leukosis virus subgroup A or B receptors resulted in efficient transduction of erythropoietin receptor or c-kit-expressing cells. Transduction of erythropoietin receptor-expressing cells mediated by bi-functional bridge proteins was found to be dependent on the dose, the correct subgroup-specific virus receptor and the correct envelope protein. Furthermore, transduction was completely abolished in the presence of anti-erythropoietin antibody.</p> <p>Conclusions</p> <p>Our results indicate that the avian sarcoma/leukosis virus bridge strategy provides a reliable approach for cell-specific lentiviral vector targeting. The background levels were lower compared to alternative strategies involving Sindbis virus strain TR339 or vesicular stomatitis virus fusion proteins.</p

Wnt5a induces ROR1 to associate with 14-3-3ζ for enhanced chemotaxis and proliferation of chronic lymphocytic leukemia cells.

Wnt5a can activate Rho GTPases in chronic lymphocytic leukemia (CLL) cells by inducing the recruitment of ARHGEF2 to ROR1. Mass spectrometry on immune precipitates of Wnt5a-activated ROR1 identified 14-3-3ζ, which was confirmed by co-immunoprecipitation. The capacity of Wnt5a to induce ROR1 to complex with 14-3-3ζ could be blocked in CLL cells by treatment with cirmtuzumab, a humanized mAb targeting ROR1. Silencing 14-3-3ζ via small interfering RNA impaired the capacity of Wnt5a to: (1) induce recruitment of ARHGEF2 to ROR1, (2) enhance in vitro exchange activity of ARHGEF2 and (3) induce activation of RhoA and Rac1 in CLL cells. Furthermore, CRISPR/Cas9 deletion of 14-3-3ζ in ROR1-negative CLL cell-line MEC1, and in MEC1 cells transfected to express ROR1 (MEC1-ROR1), demonstrated that 14-3-3ζ was necessary for the growth/engraftment advantage of MEC1-ROR1 over MEC1 cells. We identified a binding motif (RSPS857SAS) in ROR1 for 14-3-3ζ. Site-directed mutagenesis of ROR1 demonstrated that serine-857 was required for the recruitment of 14-3-3ζ and ARHGEF2 to ROR1, and activation of RhoA and Rac1. Collectively, this study reveals that 14-3-3ζ plays a critical role in Wnt5a/ROR1 signaling, leading to enhanced CLL migration and proliferation

Strangeness Enhancement in p-A Collisions: Consequences for the Interpretation of Strangeness Production in A-A Collisions

Published measurements of semi-inclusive Lambda production in p-Au collisions at the AGS are used to estimate the yields of singly strange hadrons in nucleus-nucleus A-A collisions. Results of a described extrapolation technique are shown and compared to measurements of K+ production in Si-Al, Si-Au, and Au-Au collisions at the AGS and net Lambda production in Su-Su, S-Ag, Pb-Pb, and inclusive p-A collisions at the SPS. The extrapolations can account for more than 75% of the measured strange particle yields in all of the studied systems except for very central Au-Au collisions at the AGS where RQMD comparisons suggest large re-scattering contributions.Comment: 9 pages, 4 figure

Semi-Inclusive Lambda and Kshort Production in p-Au Collisions at 17.5 GeV/c

The first detailed measurements of the centrality dependence of strangeness production in p-A collisions are presented. Lambda and Kshort dn/dy distributions from 17.5 GeV/c p-Au collisions are shown as a function of "grey" track multiplicity and the estimated number of collisions, nu, made by the proton. The nu dependence of the Lambda yield deviates from a scaling of p-p data by the number of participants, increasing faster than this scaling for nu<=5 and saturating for larger nu. A slower growth in Kshort multiplicity with nu is observed, consistent with a weaker nu dependence of K-Kbar production than Y-K production.Comment: 5 pages, 3 figures, formatted with RevTex, current version has enlarged figure catpion

Strangeness Enhancement in p+Ap+A and S+AS+A Interactions at SPS Energies

The systematics of strangeness enhancement is calculated using the HIJING and VENUS models and compared to recent data on $\,pp\,$, $\,pA\,$ and $\,AA\,$ collisions at CERN/SPS energies ($200A\,\, GeV\,$). The HIJING model is used to perform a {\em linear} extrapolation from $pp$ to $AA$. VENUS is used to estimate the effects of final state cascading and possible non-conventional production mechanisms. This comparison shows that the large enhancement of strangeness observed in $S+Au$ collisions, interpreted previously as possible evidence for quark-gluon plasma formation, has its origins in non-equilibrium dynamics of few nucleon systems. % Strangeness enhancement %is therefore traced back to the change in the production dynamics %from $pp$ to minimum bias $pS$ and central $SS$ collisions. A factor of two enhancement of $\Lambda^{0}$ at mid-rapidity is indicated by recent $pS$ data, where on the average {\em one} projectile nucleon interacts with only {\em two} target nucleons. There appears to be another factor of two enhancement in the light ion reaction $SS$ relative to $pS$, when on the average only two projectile nucleons interact with two target ones.Comment: 29 pages, 8 figures in uuencoded postscript fil

Prostate Cancer Stem Cell-Targeted Efficacy of a New-Generation Taxoid, SBT-1214 and Novel Polyenolic Zinc-Binding Curcuminoid, CMC2.24

Background Prostate cancer is the second leading cause of cancer death among men. Multiple evidence suggests that a population of tumor-initiating, or cancer stem cells (CSCs) is responsible for cancer development and exceptional drug resistance, representing a highly important therapeutic target. The present study evaluated CSC-specific alterations induced by new-generation taxoid SBT-1214 and a novel polyenolic zinc-binding curcuminoid, CMC2.24, in prostate CSCs. Principal Findings The CD133high/CD44high phenotype was isolated from spontaneously immortalized patient-derived PPT2 cells and highly metastatic PC3MM2 cells. Weekly treatment of the NOD/SCID mice bearing PPT2- and PC3MM3-induced tumors with the SBT-1214 led to dramatic suppression of tumor growth. Four of six PPT2 and 3 of 6 PC3MM2 tumors have shown the absence of viable cells in residual tumors. In vitro, SBT-1214 (100nM-1µM; for 72 hr) induced about 60% cell death in CD133high/CD44+/high cells cultured on collagen I in stem cell medium (in contrast, the same doses of paclitaxel increased proliferation of these cells). The cytotoxic effects were increased when SBT-1214 was combined with the CMC2.24. A stem cell-specific PCR array assay revealed that this drug combination mediated massive inhibition of multiple constitutively up-regulated stem cell-related genes, including key pluripotency transcription factors. Importantly, this drug combination induced expression of p21 and p53, which were absent in CD133high/CD44high cells. Viable cells that survived this treatment regimen were no longer able to induce secondary spheroids, exhibited significant morphological abnormalities and died in 2-5 days. Conclusions We report here that the SBT-1214 alone, or in combination with CMC2.24, possesses significant activity against prostate CD133high/CD44+/high tumor-initiating cells. This drug combination efficiently inhibits expression of the majority of stem cell-related genes and pluripotency transcription factors. In addition, it induces a previously absent expression of p21 and p53 (“gene wake-up”), which can potentially reverse drug resistance by increasing sensitivity to anti-cancer drugs

Charged Particle Production in Proton-, Deuteron-, Oxygen- and Sulphur-Nucleus Collisions at 200 GeV per Nucleon

The transverse momentum and rapidity distributions of net protons and negatively charged hadrons have been measured for minimum bias proton-nucleus and deuteron-gold interactions, as well as central oxygen-gold and sulphur-nucleus collisions at 200 GeV per nucleon. The rapidity density of net protons at midrapidity in central nucleus-nucleus collisions increases both with target mass for sulphur projectiles and with the projectile mass for a gold target. The shape of the rapidity distributions of net protons forward of midrapidity for d+Au and central S+Au collisions is similar. The average rapidity loss is larger than 2 units of rapidity for reactions with the gold target. The transverse momentum spectra of net protons for all reactions can be described by a thermal distribution with `temperatures' between 145 +- 11 MeV (p+S interactions) and 244 +- 43 MeV (central S+Au collisions). The multiplicity of negatively charged hadrons increases with the mass of the colliding system. The shape of the transverse momentum spectra of negatively charged hadrons changes from minimum bias p+p and p+S interactions to p+Au and central nucleus-nucleus collisions. The mean transverse momentum is almost constant in the vicinity of midrapidity and shows little variation with the target and projectile masses. The average number of produced negatively charged hadrons per participant baryon increases slightly from p+p, p+A to central S+S,Ag collisions.Comment: 47 pages, submitted to Z. Phys.

Measurement of event-by-event transverse momentum and multiplicity fluctuations using strongly intensive measures Δ[PT,N]\Delta[P_T, N] and Σ[PT,N]\Sigma[P_T, N] in nucleus-nucleus collisions at the CERN Super Proton Synchrotron

Results from the NA49 experiment at the CERN SPS are presented on event-by-event transverse momentum and multiplicity fluctuations of charged particles, produced at forward rapidities in central Pb+Pb interactions at beam momenta 20$A$, 30$A$, 40$A$, 80$A$, and 158$A$ GeV/c, as well as in systems of different size ($p+p$, C+C, Si+Si, and Pb+Pb) at 158$A$ GeV/c. This publication extends the previous NA49 measurements of the strongly intensive measure $\Phi_{p_T}$ by a study of the recently proposed strongly intensive measures of fluctuations $\Delta[P_T, N]$ and $\Sigma[P_T, N]$. In the explored kinematic region transverse momentum and multiplicity fluctuations show no significant energy dependence in the SPS energy range. However, a remarkable system size dependence is observed for both $\Delta[P_T, N]$ and $\Sigma[P_T, N]$, with the largest values measured in peripheral Pb+Pb interactions. The results are compared with NA61/SHINE measurements in $p+p$ collisions, as well as with predictions of the UrQMD and EPOS models.Comment: 12 pages, 14 figures, to be submitted to PR