The PHENIX Collaboration has measured the ratio of the yields of $\psi(2S)$ to $\psi(1S)$ mesons produced in $p$$+$$p$, $p$$+$Al, $p$$+$Au, and $^{3}$He$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV ...over the forward and backward rapidity intervals $1.2<|y|<2.2$. We find that the ratio in $p$$+$$p$ collisions is consistent with measurements at other collision energies. In collisions with nuclei, we find that in the forward ($p$-going or $^{3}$He-going) direction, the relative yield of $\psi(2S)$ mesons to $\psi(1S)$ mesons is consistent with the value measured in \pp collisions. However, in the backward (nucleus-going) direction, the $\psi(2S)$ is preferentially suppressed by a factor of $\sim$2. This suppression is attributed in some models to breakup of the weakly-bound $\psi(2S)$ through final state interactions with comoving particles, which have a higher density in the nucleus-going direction. These breakup effects may compete with color screening in a deconfined quark-gluon plasma to produce sequential suppression of excited quarkonia states.
Asymmetric nuclear collisions of p+Al, p+Au, d+Au, and ^{3}He+Au at sqrts_{NN}=200 GeV provide an excellent laboratory for understanding particle production, as well as exploring interactions among ...these particles after their initial creation in the collision. We present measurements of charged hadron production dN_{ch}/dη in all such collision systems over a broad pseudorapidity range and as a function of collision multiplicity. A simple wounded quark model is remarkably successful at describing the full data set. We also measure the elliptic flow v_{2} over a similarly broad pseudorapidity range. These measurements provide key constraints on models of particle emission and their translation into flow.
Purpose: Ion channel activity is involved in several basic cellular behaviors that are integral to metastasis (e.g., proliferation,
motility, secretion, and invasion), although their contribution to ...cancer progression has largely been ignored. The purpose
of this study was to investigate voltage-gated Na + channel (VGSC) expression and its possible role in human breast cancer.
Experimental Design: Functional VGSC expression was investigated in human breast cancer cell lines by patch clamp recording. The contribution
of VGSC activity to directional motility, endocytosis, and invasion was evaluated by in vitro assays. Subsequent identification of the VGSC α-subunit(s) expressed in vitro was achieved using reverse transcription-PCR, immunocytochemistry, and Western blot techniques and used to investigate VGSCα
expression and its association with metastasis in vivo .
Results: VGSC expression was significantly up-regulated in metastatic human breast cancer cells and tissues, and VGSC activity potentiated
cellular directional motility, endocytosis, and invasion. Reverse transcription-PCR revealed that Na v 1.5, in its newly identified “neonatal” splice form, was specifically associated with strong metastatic potential in vitro and breast cancer progression in vivo . An antibody specific for this form confirmed up-regulation of neonatal Na v 1.5 protein in breast cancer cells and tissues. Furthermore, a strong correlation was found between neonatal Na v 1.5 expression and clinically assessed lymph node metastasis.
Conclusions: Up-regulation of neonatal Na v 1.5 occurs as an integral part of the metastatic process in human breast cancer and could serve both as a novel marker of
the metastatic phenotype and a therapeutic target.
Jet production rates are measured in p+p and d+Au collisions at sqrts_{NN}=200 GeV recorded in 2008 with the PHENIX detector at the Relativistic Heavy Ion Collider. Jets are reconstructed using the ...R=0.3 anti-k_{t} algorithm from energy deposits in the electromagnetic calorimeter and charged tracks in multiwire proportional chambers, and the jet transverse momentum (p_{T}) spectra are corrected for the detector response. Spectra are reported for jets with 12<p_{T}<50 GeV/c, within a pseudorapidity acceptance of |η|<0.3. The nuclear-modification factor (R_{dAu}) values for 0%-100% d+Au events are found to be consistent with unity, constraining the role of initial state effects on jet production. However, the centrality-selected R_{dAu} values and central-to-peripheral ratios (R_{CP}) show large, p_{T}-dependent deviations from unity, challenging the conventional models that relate hard-process rates and soft-particle production in collisions involving nuclei.
PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine ...diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations.
We present the first measurement of elliptic (v(2)) and triangular (v(3)) flow in high-multiplicity (3)He+Au collisions at √(s(NN))=200 GeV. Two-particle correlations, where the particles have a ...large separation in pseudorapidity, are compared in (3)He+Au and in p+p collisions and indicate that collective effects dominate the second and third Fourier components for the correlations observed in the (3)He+Au system. The collective behavior is quantified in terms of elliptic v(2) and triangular v(3) anisotropy coefficients measured with respect to their corresponding event planes. The v(2) values are comparable to those previously measured in d+Au collisions at the same nucleon-nucleon center-of-mass energy. Comparisons with various theoretical predictions are made, including to models where the hot spots created by the impact of the three (3)He nucleons on the Au nucleus expand hydrodynamically to generate the triangular flow. The agreement of these models with data may indicate the formation of low-viscosity quark-gluon plasma even in these small collision systems.
Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of ...standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14;18) and t(11;14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n=56), mantle cell lymphoma (n=54), marginal zone lymphoma (n=41) and follicular lymphoma (n=109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.
Voltage-gated sodium channel (VGSC) activity has previously been reported in endothelial cells (ECs). However, the exact isoforms of VGSCs present, their mode(s) of action, and potential role(s) in ...angiogenesis have not been investigated. The main aims of this study were to determine the role of VGSC activity in angiogenic functions and to elucidate the potentially associated signaling mechanisms using human umbilical vein endothelial cells (HUVECs) as a model system. Real-time PCR showed that the primary functional VGSC α- and β-subunit isoforms in HUVECs were Nav1.5, Nav1.7, VGSCβ1, and VGSCβ3. Western blots verified that VGSCα proteins were expressed in HUVECs, and immunohistochemistry revealed VGSCα expression in mouse aortic ECs in vivo. Electrophysiological recordings showed that the channels were functional and suppressed by tetrodotoxin (TTX). VGSC activity modulated the following angiogenic properties of HUVECs: VEGF-induced proliferation or chemotaxis, tubular differentiation, and substrate adhesion. Interestingly, different aspects of angiogenesis were controlled by the different VGSC isoforms based on TTX sensitivity and effects of siRNA-mediated gene silencing. Additionally, we show for the first time that TTX-resistant (TTX-R) VGSCs (Nav1.5) potentiate VEGF-induced ERK1/2 activation through the PKCα-B-RAF signaling axis. We postulate that this potentiation occurs through modulation of VEGF-induced HUVEC depolarization and Ca(2+)(i). We conclude that VGSCs regulate multiple angiogenic functions and VEGF signaling in HUVECs. Our results imply that targeting VGSC expression/activity could be a novel strategy for controlling angiogenesis.
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