Ar Targets Research Articles

Transverse momentum of ionized atoms and diatomic molecules acquired in collisions with fast highly charged heavy ions

Using a recoil-ion momentum spectrometer (RIMS), transverse momenta (${q}_{\ensuremath{\perp}}$) of recoil atomic and molecular ions emerging from collisions between 2.5-MeV/u Xe${}^{34+}$ projectiles and neutral Ne, Ar, CO, N${}_{2}$, and O${}_{2}$ gases were measured as a function of the degree of target ionization. For the molecular targets the resulting distributions of ${q}_{\ensuremath{\perp}}$ corresponding to different dissociation channels were separated. Measurements with all the targets were performed under virtually identical conditions so that the results could be directly compared in detail. It was found that the shapes of the ${q}_{\ensuremath{\perp}}$ distributions are characterized by single asymmetric peaks and that, at least in the vicinity of their maximum values, they are well described by Weibull functions. Except for the Ar target, the velocities corresponding to the maxima of the ${q}_{\ensuremath{\perp}}$ distributions were found to follow (within the uncertainties of the results) a universal function of the target charge-to-mass number ratio for values up to 0.33. For larger charge-to-mass number ratios the results for the molecular targets appear to remain universal, but are slightly lower than the results for the Ne target. A more elaborate scaling was required to obtain a universal function that describes the low-charge-state results for Ne and Ar targets in a similar way. For different dissociation channels of the same parent molecular ion with charge states exceeding 6+, significant differences were found between the measured ${q}_{\ensuremath{\perp}}$ distributions. These differences were ascribed to increases in the ionization potential and to more prominent contributions from target-to-projectile electron transfer for the more asymmetric dissociation channels. For symmetric and nearly symmetric molecular dissociation channels the fragments with combined charge number $Q$ exceeding 9 for N${}_{2}$ and 10 for O${}_{2}$ were found to be distributed with a reduced probability at angles close to 90\ifmmode^\circ\else\textdegree\fi{} relative to the beam direction. The magnitude of this effect was found to depend on the number of electrons removed in addition to one half of the number of available electrons ($Q$--$Z$). On the other hand, for highly asymmetric dissociation channels the angular distributions seem to indicate that the fragments of highly charged molecular ions may be distributed with an enhanced probability at angles close to 90\ifmmode^\circ\else\textdegree\fi{} relative to the beam direction. A slight dependence of the ${q}_{\ensuremath{\perp}}$ distribution on molecular orientation was found to be present for the symmetric and nearly symmetric dissociation channels having $Q--Z\ensuremath{\geqslant}0$. The magnitude of this effect also seems to be determined by the value of $Q$--$Z$.

Target Dependence of Single-Electron-Capture Cross Sections for Slow Be, B, C, Fe, Ni, and W Ions Colliding with Atomic and Molecular Targets

Single-electron-capture cross sections σ10 for W+ projectile ions on Ar and Kr atomic gas targets at 10 keV (55 eV/u) and on H2, D2, CH4, C2H6, and C3H8 molecular gas targets at between 5.0 and 10 keV (27 and 55 eV/u) were experimentally derived for the first time. With our published single-electron-capture cross sections σq q-1 for Beq+, Bq+, Cq+, Feq+, Niq+, and Wq+ (q = 1 for Fe; q = 1, 2 for the others) ions in low energy, an attempt was made to draw scaling behavior of single-electron-capture cross sections for such slow low-q ions on target species. Established scaling formulas are found to reproduce the measured cross sections generally within a magnitude and with higher precision for specific initial charge state and target species.

Abstract 2123: Tetrandrine impairs prostate cancer cell survival in part by inhibiting AR signaling pathway.

Abstract Prostate cancer (PCa) is the second leading cause of cancer deaths in men, and the majority of prostate cancer deaths are a result of emergence of castrate resistant phenotype. Our previous studies indicated that Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the root of Stephania tetrandra inhibited cell cycle progression and promoted growth arrest at lower concentrations and promoted apoptosis at higher concentrations and at longer time points. AR signaling is known to play a critical role in androgen responsive prostate cancer cells. In the present studies we evaluated the effects of TET on AR signaling in androgen dependent (LNCaP cells) as well as castrate resistant (C4 and C42B cells, castrate resistant lineages of LNCaP cells) prostate cancer cells. Exposure of LNCaP cells to Tet resulted in a dose and time dependent decrease in PSA protein (cell associated as well as secreted PSA). Further analysis revealed that Tet also decreased PSA mRNA as well as PSA promoter activity, suggesting that Tet induced decrease in PSA was a result of inhibition of PSA transcription. Since PSA is known to be an AR responsive gene, these results led us to investigate the effects of Tet on AR signaling. Results from these studies revealed that Tet inhibited AR activity as measured by TARP promoter assay. Taken together these studies suggest that Tet targets AR signaling pathway effectively blocking AR target genes. In summary our results suggest that Tet by inhibiting AR signaling pathway may work as an effective therapeutic agent in prostate cancer, for which there is no cure to date. Grant Support: Studies supported in part by VA Merit Award-01BX001258 (HK), NIH/NCI R01CA161880 (HK) and Department of Surgery, School of Medicine chair commitment (HK). Citation Format: Sweaty Koul, Hari K. Koul. Tetrandrine impairs prostate cancer cell survival in part by inhibiting AR signaling pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2123. doi:10.1158/1538-7445.AM2013-2123

Neutrino detection in the ArgoNeuT LAr TPC

ArgoNeuT, a Liquid Argon Time Projection Chamber (LAr-TPC), has collected thousands of neutrino and anti-neutrino events between 0.1 and 10 GeV in the NuMI beamline at Fermilab (FNAL). Among other issues, the experiment will measure the cross section of the neutrino and anti-neutrino Charged Current Quasi-Elastic (CC QE) interaction on Ar target and analyze the vertex activity associated with such events. ArgoNeuT data analysis and FSI studies in progress are described and first measurements of inclusive muon neutrino Charged Current differential cross sections on Argon are reported.

Modeling Truncated AR Expression in a Natural Androgen Responsive Environment and Identification of RHOB as a Direct Transcriptional Target

Recent studies identifying putative truncated androgen receptor isoforms with ligand-independent activity have shed new light on the acquisition of androgen depletion independent (ADI) growth of prostate cancer. In this study, we present a model system in which a C-terminally truncated variant of androgen receptor (TC-AR) is inducibly expressed in LNCaP, an androgen-dependent cell line, which expresses little truncated receptor. We observed that when TC-AR is overexpressed, the endogenous full length receptor (FL-AR) is transcriptionally downmodulated. This in essence allows us to “replace” FL-AR with TC-AR and compare their individual properties in exactly the same genetic and cellular background, which has not been performed before. We show that the TC-AR translocates to the nucleus, activates transcription of AR target genes in the absence of DHT and is sufficient to confer ADI growth to the normally androgen dependent LNCaP line. We also show that while there is significant overlap in the genes regulated by FL- and TC-AR there are also differences in the respective suites of target genes with each AR form regulating genes that the other does not. Among the genes uniquely activated by TC-AR is RHOB which is shown to be involved in the increased migration and morphological changes observed in LN/TC-AR, suggesting a role of RHOB in the regulation of androgen-independent behavior of prostate cancer cells.

Accurate semi-empirical potentials for positron scattering by atoms

Starting from adiabatic potentials for positron interaction with atoms, an empirical scaling is introduced to account for positron-electron correlation, leading to relevant improvements. For example, the Ransauer minimum is predict for Ar target and has its position corrected for Ne target. Elastic differential cross sections are generated for Be and Mg as well.

A molecular beam scattering investigation of methanol–noble gas complexes: Characterization of the isotropic potential and insights into the nature of the interaction

Integral cross section experiments involving rotationally hot CH3OH projectiles and noble gas (Ng=Ne, Ar, Kr and Xe) targets are reported for the first time. Measured data have been exploited to characterize the phenomenological radial interaction in the CH3OH–Ng weakly bound complexes. Potential energy surfaces for all the systems have been formulated on the basis of a pairwise additive multicenter model. The comparison of model predictions with the most relevant experimental findings suggests that in CH3OH–Ng complexes, at variance with the behavior of the analogous complexes involving water or ammonia, the interaction is mainly due to van der Waals and induction components.

Investigation of slow collisions for (quasi) symmetric heavy systems: what can be extracted from high resolution x-ray spectra

We present a new experiment on (quasi) symmetric collision systems at low velocity, namely Ar17 + ions (v = 0.53 au) on gaseous Ar and N2 targets, using low- and high-resolution x-ray spectroscopy. Thanks to an accurate efficiency calibration of the spectrometers, we extract absolute x-ray emission cross sections combining low-resolution x-ray spectroscopy and a complete determination of the ion beam–gas jet target overlap. Values with improved uncertainty are found in agreement with previous results (Tawara et al 2001 Phys. Rev. A 64 042712). Resolving the whole He-like Ar16 + Lyman series from n = 2–10 with our crystal spectrometer enables us to determine precisely the distribution of the electron capture probability and the preferential npref level of the selective single-electron capture. Evaluation of cross sections for this process as well as for the contribution of multiple-capture is carried out. Their sensitivity to the ℓ-distribution of n levels populated by single-electron capture is clearly demonstrated, providing a stringent benchmark for theories. In addition, the hardness ratio is extracted and the influence of the decay of the metastable 1s2s 3S1 state on this ratio is discussed.

Ab initiostudy of charge exchange in collisions of B2+ions with Ne and Ar targets

The electron-capture processes in collisions of B${}^{2+}$ ions with neon and argon targets have been studied theoretically using ab initio multireference configuration interaction potential-energy curves and nonadiabatic couplings. The cross sections for the simple capture process have been calculated using the semiclassical collision methods in the 10${}^{\ensuremath{-}2}$--2-a.u. velocity range (${E}_{\mathrm{lab}}$ \ensuremath{\approx} [0.02--1080 keV]) and have been compared with the available experimental data. The charge-transfer mechanism is analyzed with regard to the radial and rotational interactions and appears to be quite different for both systems. Good agreement is found with the measured cross sections.

Abstract IA3: Functional implications of relocation of regulated transcription units in prostate cancer

Abstract Despite the long-standing recognition of distinct subnuclear architectural features and the recent discovery of noncoding RNAs (ncRNAs), their potential interacting roles in gene regulation remain elusive. We have found that two ncRNAs, TUG1 and NEAT2, located in Polycomb body (PcGs) and interchromatin granules, respectively, control relocation of growth control genes required for regulation of cell cycle between these two subnuclear structures, depending on the status of Polycomb 2 protein (Pc2) methylation in response to growth signals. These ncRNAs direct the assembly of multiple transcriptional co-repressor/coactivator complexes and, surprisingly, can alter “reading” of the histone tail marks by the Pc2 chromodomain, thereby specifying growth control gene expression and cell proliferation in a spatially organized manner. Binding of NEAT2 to demethylated Pc2, which promotes the SUMOylation of E2F1, which culminates in activation of the growth control gene program. These observations provide a molecular logic integrating actions of transcription factor/co-regulators, non-histone protein methylation, and ncRNAs resident in distinct subnuclear architectural structures to achieve coordinated programs of regulated gene expression in the three-dimensional space of the nucleus. We also will present data linking these strategies to mechanisms of ligand-induced activation of AR target genes in prostate cancer cells. Citation Format: Liuqing Yang, Chunru Lin, Esperanza Nunez, Wenbo Li, Eugin Destici, Michael G Rosenfeld. Functional implications of relocation of regulated transcription units in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA3.

Soft X-ray characterization of an elongated gas-puff target dedicated for laser–matter interaction experiments and high harmonic generation

A slit-shaped elongated nozzle, capable of forming an extended gas density profile, is presented and studied in detail. Argon and xenon target density backlighting measurements revealed the elongated density profiles with gas density that can be tuned by changing valve backing pressure and valve timing. Two dimensional density maps for Ar and Xe targets, obtained at soft X-ray wavelengths around 7Å, are shown and spatially characterized. Moreover the influence of valve backing pressure and valve timing on gas puff target density is studied. This geometry of the nozzle has potential applications in high harmonic generation for an efficient conversion of femto-second duration, intense infrared pulses to extreme ultraviolet (EUV) region.

Probing the dynamics of collision induced processes in atoms, molecules and solid surfaces with impact of keV electrons

Collision induced excitation and ionization of atoms and molecules by energetic electrons play an important role in thermonuclear fusion plasmas, and in atmospheric science. In this paper, a brief review of the recent experimental works that have been carried out in the Atomic Physics Laboratory at Banaras Hindu University, Varanasi is presented. Some selected examples of the collision induced processes involved in impact of keV electrons with atoms, molecules and solid surfaces is highlighted. In particular, the results obtained on the multiple- and dissociative ionization of Ar atom and SF6 molecule, the electron backscattering from a pure thick W target and on the electron bremsstrahlung emission from gaseous Ar and thick solid Ti targets are presented and discussed.

Stopping of hypervelocity clusters in solids

Using molecular-dynamics simulations, we study the processes underlying the stopping of energetic clusters upon impact in matter. We investigate self-bombardment of both a metallic (Cu) and a van-der-Waals bonded (frozen Ar) target. Clusters with sizes up to N = 104 atoms and with energies per atom of E/N = 0.1–1600 eV atom−1 were studied. We find that the stopping force exerted on a cluster follows an N2/3-dependence with cluster size N; thus large clusters experience less stopping than equi-velocity atoms. In the course of being stopped, the cluster is strongly deformed and attains a roughly pancake shape. Due to the cluster inertia, maximum deformation occurs later than the maximum stopping force. The time scale of projectile stopping is set by t0, the time the cluster needs to cover its own diameter before impacting the target; it thus depends on both cluster size and velocity. The time when the cluster experiences its maximum stopping force is around (0.7–0.8)t0. We find that the cluster is deformed with huge strain rates of around 1/2t0; this amounts to 1011–1013 s−1 for the cases studied here.

The selective inhibitory effect of a synthetic tanshinone derivative on prostate cancer cells

Androgen receptor (AR) is the main therapeutic target for the treatment of prostate cancer (PCa). Anti-androgens to reduce or prevent androgens binding to AR are widely used to suppress AR-mediated PCa growth; however, the androgen depletion therapy (ADT) is only effective for a short period of time. Here we tested PTS33, a new sodium derivative of cryptotanshinone, which can effectively inhibit the DHT-induced AR transactivation and PCa cell growth, and then explored the effects of PTS33 on inhibiting the expressions of AR target genes and proteins. PCa cells, LNCaP, CWR22Rv1, C4-2, PC-3, and DU145, were treated with PTS33 and luciferase assay was used to evaluate the ability of each to regulate AR transactivation. RT-PCR was used to evaluate the mRNA levels of AR target genes such as PSA, TMPRSS2, and TMEPA1. Western blot was used to determine AR, PSA, estrogen receptor alpha (ERα), glucocorticoid receptor (GR), and progesterone receptor (PR) protein expression. Cell growth and IC50 were determined by MTT assay after 48 hr treatment. Our data showed that PTS33 selectively inhibits AR activities, but PTS33 does not repress the activities of other nuclear receptors, including ERα, GR, and PR. At a low concentration, 2 µM of PTS33 effectively suppresses the growth of AR-positive PCa cells, and has little effect on AR-negative PCa cells. Furthermore, our data indicated that PTS33 could modulate AR transactivation and suppress the AR target genes (PSA, TMPRSS2, and TMEPA1) expression in both androgen responsive PCa LNCaP cells and castration-resistant C4-2 cells. In addition, PTS33 can also inhibit estrogen/Δ5-androstenediol induced AR activities. The mechanistic studies indicate that PTS33 can inhibit AR function by suppression of AR protein expression, the AR N-C interaction, and AR-coregulator interaction. PTS33 has shown a good efficacy to inhibit AR transactivation, block AR regulated gene expression, and reduce cell growth in AR positive PCa cells. The structure of PTS33 could be used as a base for development of novel AR signaling inhibitors to treat PCa.

Electron loss of heavy many-electron ions in relativistic collisions with neutral atoms

Electron-loss processes arising in collisions of heavy many-electron ions (like U28+) with neutral atoms (H, N, Ar) are considered over a wide energy range including relativistic energies. Various computer codes (LOSS, LOSS-R, HERION, and RICODE), created for calculation of the electron-loss cross sections, and their capability are described. Recommended data on the electron-loss cross sections of U28+ ions colliding with H, N, Ar targets and predicted lifetimes of U28+ ion beams in accelerator are given. Calculated electronloss cross sections are compared with available experimental data and other calculations.

The ArgoNeuT LAr-TPC: A dedicated experiment for neutrino cross section measurement at FNAL

ArgoNeuT, a Liquid Argon Time Projection Chamber (LAr-TPC), has recently collected thousands of neutrino and anti-neutrino events between 0.1 and 10 GeV in the NuMI beamline at Fermilab (FNAL). Among other issues, the experiment will measure the cross section of the neutrino and anti-neutrino Charged Current Quasi-Elastic (CCQE) interaction on Ar target and analyze the vertex activity associated with such events. Outcomes from the reconstruction of the events provide the main subject of this paper.

Abstract 2879: Mechanisms of integration for androgen receptor and phosphatidylinositol 3-kinase signaling in estrogen receptor negative class A breast cancer

Abstract Effective targeted therapies for estrogen receptor-negative, progesterone receptor-negative breast cancer remains elusive. Previously, we identified a new subclass of ER- / PR- / AR+ breast cancers as Class A [1]. Class A breast cancer derived cell lines are growth inhibited by anti-androgens (bicalutamide) and stimulated by testosterone [1]. Interestingly, these cell lines harbor mutations in the PIK3CA gene leading to persistent activation of the PI3Kinase pathway [2,3]. In this report we examined the incidence of PIK3CA mutations in ER-/PR-/AR+ breast cancers. We also investigated the role of PI3K/AKT signaling on AR activity and growth of Class A cancer derived cell lines. We examined 100 primary ER-/PR- breast tumors and determined that 28% express AR by IHC. By Sequenom analysis we determined that 12% contain mutations in the PIK3CA gene within the canonical hot spots (exon 9,20). The expression of AR in ER- / PR- breast cancers positively correlated with PIK3CA mutations (p=0.0039), pAkt levels (p=0.01), and HER2 (p=0.05) expression. In addition, we observed a strong association between HER2 expression and pAkt levels in ER-/PR-/AR+ breast cancers. A number of in vitro studies were performed in order to examine the potential functional consequences of PI3K signaling in Class A breast cancer cell lines (MDA-MB-453 and HCC202). We first determined that the cell lines harboring PIK3CA mutations were more responsive to PI3K inhibitors for growth inhibition compared to class B cell lines (ER-,PR-,AR- breast cancer subclass [1]) lacking PIK3CA mutations. Induction of proliferation by synthetic androgen in class A breast cancer cell lines is decreased by androgen antagonist as well as PI3K inhibitors and the combination of both inhibitors had an additive effect. We also examined serine phosphorylated AR levels (a modification leading to enhanced AR transcriptional activity), AR transcriptional activity and the expression of AR target genes GGT1 and CYP4F8 in class A breast cancer cell lines. When cells were incubated with androgen agonists, the levels of all three elements were increased compared to vehicle control. Treatment with a PI3K inhibitor decreased the levels of all three elements compared to vehicle control. When cells were treated with the combination of the androgen agonist and a PI3K inhibitor, the levels of all three elements were higher than the inhibitor but lower than the agonist alone. These findings suggest that components of PI3K/AKT pathway can modulate AR activity suggesting a putative cross-talk between AR and PI3K pathways. This potential cooperative effect represents a new paradigm in targeted therapeutic strategies directed at the biological signal integration contributing to AR+ / ER- / PR- cancers. 1. Doane, A.S. Oncogene, 2006. 25(28): p. 3994 2. Kataoka, Y. Ann Oncol, 2010. 21(2): p. 255 3. Oda, K. Cancer Res, 2008. 68(19): p. 8127 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2879. doi:10.1158/1538-7445.AM2011-2879

A Feedback Loop between Androgen Receptor and ERK Signaling in Estrogen Receptor-Negative Breast Cancer

Estrogen receptor (ER)-negative breast cancer is heterogeneous, and the biology of this disease has remained poorly understood. Molecular apocrine is a subtype of ER-negative breast cancer that is characterized by the overexpression of steroid-response genes such as AR and a high rate of ErbB2 amplification. In this study, we have identified a positive feedback loop between the AR and extracellular signal-regulated kinase (ERK) signaling pathways in molecular apocrine breast cancer. In this process, AR regulates ERK phosphorylation and kinase activity. In addition, AR inhibition results in the down-regulation of ERK target proteins phospho-RSK1, phospho-Elk-1, and c-Fos using an in vivo molecular apocrine model. Furthermore, we show that AR-mediated induction of ERK requires ErbB2, and AR activity, in turn, regulates ErbB2 expression as an AR target gene. These findings suggest that ErbB2 is an upstream connector between the AR and ERK signaling pathways. Another feature of this feedback loop is an ERK-mediated regulation of AR. In this respect, the inhibition of ERK phosphorylation reduces AR expression and CREB1-mediated transcriptional regulation of AR acts as a downstream connector between the AR and ERK signaling pathways in molecular apocrine cells. Finally, we demonstrate that AR-positive staining is associated with the overexpression of ERK signaling targets phospho-Elk-1 and c-Fos in ER-negative breast tumors, which further supports a cross-regulation between the AR and ERK signaling pathways in molecular apocrine subtype. This study demonstrates an AR-ERK feedback loop in ER-negative breast cancer with significant biologic and therapeutic implications in this disease.

Charge-Transfer Cross Sections of H+ Ions in Collisions with Noble Gas Atoms in the Energy Range below 4.0 keV

Charge-transfer cross sections in collisions of H+ ions with the ground state He, Ar, Kr, and Xe atoms have been measured in the energy range below 4.0 keV with the initial growth rate method. These observed cross sections are also compared with previously published experimental data and theoretical predictions. In the He and Ar targets, it is found that some previous experimental data deviate significantly from the present observed cross sections as the collision energy decreases. It has been found that in the Kr and Xe targets, the energy dependence of the present observed cross sections behaves as “near-resonant” charge transfer.

512 NCIC CTG IND.181: Phase I study of AT9283 given as a weekly 24 hour infusion

Point mutations in the AR ligand-binding domain (LBD) can result in altered AR structures leading to changes of ligand specificity and functions. AR mutations associated to prostate cancer (PCa) have been shown to result in receptor activation by non-androgenic substances and anti-androgenic drugs. Two AR mutations known to alter the function of anti-androgens are the ART877A mutation, which is frequently detected mutation in PCa tumors and the ARW741C that is rare and has been derived in vitro following exposure of cells to the anti-androgen bicalutamide. AR activation by non-androgenic environmental substances has been suggested to affect PCa progression. In the present study we investigated the effect of AR mutations (ARW741C and ART877A) on the transcriptional activation following exposure of cells to an androgenic brominated flame retardant, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH, also named DBE-DBCH). The AR mutations resulted in higher interaction energies and increased transcriptional activation in response to TBECH diastereomer exposures. The ART877A mutation rendered AR highly responsive to low levels of DHT and TBECH and led to increased AR nuclear translocation. Gene expression analysis showed a stronger induction of AR target genes in LNCaP cells (ART877A) compared to T-47D cells (ARWT) following TBECH exposure. Furthermore, AR knockdown experiments confirmed the AR dependency of these responses. The higher sensitivity of ART877A and ARW741C to low levels of TBECH suggests that cells with these AR mutations are more susceptible to androgenic endocrine disrupters.