Spin-Peierls and Antiferromagnetic Phases in Cu{1-x}Zn{x}GeO{3}: A Neutron Scattering Study

Comprehensive neutron scattering studies were carried out on a series of high-quality single crystals of Cu_{1-x}Zn_xGeO_3. The Zn concentration, x, was determined for each sample using Electron Probe Micro-Analysis. The measured Zn concentrations were found to be 40-80% lower than the nominal values. Nevertheless the measured concentrations cover a wide range which enables a systematic study of the effects due to Zn-doping. We have confirmed the coexistence of spin-Peierls (SP) and antiferromagnetic (AF) orderings at low temperatures and the measured phase diagram is presented. Most surprisingly, long-range AF ordering occurs even in the lowest available Zn concentration, x=0.42%, which places important constraints on theoretical models of the AF-SP coexistence. Magnetic excitations are also examined in detail. The AF excitations are sharp at low energies and show no considerable broadening as x increases indicating that the AF ordering remains long ranged for x up to 4.7%. On the other hand, the SP phase exhibits increasing disorder as x increases, as shown from the broadening of the SP excitations as well as the dimer reflection peaks.Comment: 17 preprint style pages, 9 postscript files included. Submitted to Phys. Rev. B. Also available from http://insti.physics.sunysb.edu/~mmartin/pubs.htm

Cooperative benefit for the combination of rapamycin and imatinib in tuberous sclerosis complex neoplasia

Tuberous sclerosis (TS) is a common autosomal-dominant disorder characterized by tumors of the skin, lung, brain, and kidneys. Monotherapy with rapamycin however resulted in partial regression of tumors, implying the involvement of additional pathways. We have previously implicated platelet-derived growth factor-BB in TS-related tumorigenesis, thus providing a rationale for a combination of mTOR/PDGF blockade using rapamycin and imatinib. Here, we test this combination using a well-established preclinical model of cutaneous tumorigenesis in TS, tsc2ang1 cells derived from a skin tumor from a mouse heterozygous for tsc2. Treatment of tsc2ang1 cells with a combination of rapamycin and imatinib led to an inhibition of proliferation compared with either vehicle treatment or treatment with rapamycin or imatinib monotherapy. Combination therapy also led to a decrease in Akt activation. Potent in vivo activity in animal experiments by combination therapy was noted, without toxicity to the animals. Our findings provide a rationale for the combined use of rapamycin and imatinib, both FDA approved drugs, for the treatment of TS

Cetuximab Augments Cytotoxicity with Poly (ADP-Ribose) Polymerase Inhibition in Head and Neck Cancer

Overexpression of the epidermal growth factor receptor (EGFR) is a hallmark of head and neck cancers and confers increased resistance and inferior survival rates. Despite targeted agents against EGFR, such as cetuximab (C225), almost half of treated patients fail this therapy, necessitating novel therapeutic strategies. Poly (ADP-Ribose) polymerase (PARP) inhibitors (PARPi) have gained recent attention due to their unique selectivity in killing tumors with defective DNA repair. In this study, we demonstrate that C225 enhances cytotoxicity with the PARPi ABT-888 in UM-SCC1, UM-SCC6, and FaDu head and neck cancer cells. The mechanism of increased susceptibility to C225 and PARPi involves C225-mediated reduction of non-homologous end-joining (NHEJ)- and homologous recombination (HR)-mediated DNA double strand break (DSB) repair, the subsequent persistence of DNA damage, and activation of the intrinsic apoptotic pathway. By generating a DSB repair deficiency, C225 can render head and neck tumor cells susceptible to PARP inhibition. The combination of C225 and the PARPi ABT-888 can thus be an innovative treatment strategy to potentially improve outcomes in head and neck cancer patients. Furthermore, this strategy may also be feasible for other EGFR overexpressing tumors, including lung and brain cancers

Tris DBA palladium is highly effective against growth and metastasis of pancreatic cancer in an orthotopic model

Pancreatic carcinoma ranks among the most lethal of human cancers. Besides late detection, other factors contribute to its lethality, including a high degree of chemoresistance, invasion, and distant metastases. Currently, the mainstay of therapy involves resection of local disease in a minority of patients (Whipple procedure) and systemic gemcitabine. While systemic chemotherapy has some benefit, even with optimal treatment, the five year survival after diagnosis is dismal. Thus, treatment of pancreatic carcinoma remains a tremendous unmet need. The organometallic compound tris DBA palladium is a potent inhibitor of N-myristoyltransferase 1 (NMT1), an enzyme that catalyzes the transfer of myristate to protein substrates. This compound is highly effective in vivo against murine models of melanoma with both mutant and wild type b-RAF genotypes. Based upon the signaling similarities between melanoma and pancreatic carcinoma, we evaluated the efficacy of tris DBA palladium in vitro and in vivo against pancreatic carcinoma. We found that tris DBA palladium decreased proliferation and colony formation of pancreatic cancer cells in vitro. In an orthotopic mouse model, tris DBA palladium was highly active in inhibiting growth, ascites production, and distant metastases in vivo. Furthermore, tris DBA palladium impaired chemotaxis and inhibited cilia formation in Pan02 cells in a NMT1-dependent manner. We propose that NMT1 is a novel regulator of cilia formation and tris DBA palladium a novel inhibitor of cilia formation and metastasis in pancreatic cancer. Thus, further evaluation of tris DBA palladium for the treatment of pancreatic cancer is warranted

Pion, kaon, proton and anti-proton transverse momentum distributions from p+p and d+Au collisions at sNN=200\sqrt{s_{NN}} = 200 GeV

Identified mid-rapidity particle spectra of $\pi^{\pm}$, $K^{\pm}$, and $p(\bar{p})$ from 200 GeV p+p and d+Au collisions are reported. A time-of-flight detector based on multi-gap resistive plate chamber technology is used for particle identification. The particle-species dependence of the Cronin effect is observed to be significantly smaller than that at lower energies. The ratio of the nuclear modification factor ($R_{dAu}$) between protons $(p+\bar{p})$ and charged hadrons ($h$) in the transverse momentum range $1.2<{p_{T}}<3.0$ GeV/c is measured to be $1.19\pm0.05$(stat)$\pm0.03$(syst) in minimum-bias collisions and shows little centrality dependence. The yield ratio of $(p+\bar{p})/h$ in minimum-bias d+Au collisions is found to be a factor of 2 lower than that in Au+Au collisions, indicating that the Cronin effect alone is not enough to account for the relative baryon enhancement observed in heavy ion collisions at RHIC.Comment: 6 pages, 4 figures, 1 table. We extended the pion spectra from transverse momentum 1.8 GeV/c to 3. GeV/

Demonstration of the temporal matter-wave Talbot effect for trapped matter waves

We demonstrate the temporal Talbot effect for trapped matter waves using ultracold atoms in an optical lattice. We investigate the phase evolution of an array of essentially non-interacting matter waves and observe matter-wave collapse and revival in the form of a Talbot interference pattern. By using long expansion times, we image momentum space with sub-recoil resolution, allowing us to observe fractional Talbot fringes up to 10th order.Comment: 17 pages, 7 figure

Absorbing customer knowledge: how customer involvement enables service design success

Customers are a knowledge resource outside of the firm that can be utilized for new service success by involving them in the design process. However, existing research on the impact of customer involvement (CI) is inconclusive. Knowledge about customers’ needs and on how best to serve these needs (articulated in the service concept) is best obtained from customers themselves. However, codesign runs the risk of losing control of the service concept. This research argues that of the processes of external knowledge, acquisition (via CI), customer knowledge assimilation, and concept transformation form a capability that enables the firm to exploit customer knowledge in the form of a successful new service. Data from a survey of 126 new service projects show that the impact of CI on new service success is fully mediated by customer knowledge assimilation (the deep understanding of customers’ latent needs) and concept transformation (the modification of the service concept due to customer insights). However, its impact is more nuanced. CI exhibits an “∩”-shaped relationship with transformation, indicating there is a limit to the beneficial effect of CI. Its relationship with assimilation is “U” shaped, suggesting a problem with cognitive inertia where initial learnings are ignored. Customer knowledge assimilation directly impacts success, while concept transformation only helps success in the presence of resource slack. An evolving new service design is only beneficial if the firm has the flexibility to adapt to change

An anatomic gene expression atlas of the adult mouse brain

Studying gene expression provides a powerful means of understanding structure-function relationships in the nervous system. The availability of genome-scale in situ hybridization datasets enables new possibilities for understanding brain organization based on gene expression patterns. The Anatomic Gene Expression Atlas (AGEA) is a new relational atlas revealing the genetic architecture of the adult C57Bl/6J mouse brain based on spatial correlations across expression data for thousands of genes in the Allen Brain Atlas (ABA). The AGEA includes three discovery tools for examining neuroanatomical relationships and boundaries: (1) three-dimensional expression-based correlation maps, (2) a hierarchical transcriptome-based parcellation of the brain and (3) a facility to retrieve from the ABA specific genes showing enriched expression in local correlated domains. The utility of this atlas is illustrated by analysis of genetic organization in the thalamus, striatum and cerebral cortex. The AGEA is a publicly accessible online computational tool integrated with the ABA (http://mouse.brain-map.org/agea)

Azimuthal anisotropy at RHIC: the first and fourth harmonics

We report the first observations of the first harmonic (directed flow, v_1), and the fourth harmonic (v_4), in the azimuthal distribution of particles with respect to the reaction plane in Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Both measurements were done taking advantage of the large elliptic flow (v_2) generated at RHIC. From the correlation of v_2 with v_1 it is determined that v_2 is positive, or {\it in-plane}. The integrated v_4 is about a factor of 10 smaller than v_2. For the sixth (v_6) and eighth (v_8) harmonics upper limits on the magnitudes are reported.Comment: 6 pages with 3 figures, as accepted for Phys. Rev. Letters The data tables are at http://www.star.bnl.gov/central/publications/pubDetail.php?id=3

LMTK3 confers chemo-resistance in breast cancer

Lemur tyrosine kinase 3 (LMTK3) is an oncogenic kinase that is involved in different types of cancer (breast, lung, gastric, colorectal) and biological processes including proliferation, invasion, migration, chromatin remodeling as well as innate and acquired endocrine resistance. However, the role of LMTK3 in response to cytotoxic chemotherapy has not been investigated thus far. Using both 2D and 3D tissue culture models, we found that overexpression of LMTK3 decreased the sensitivity of breast cancer cell lines to cytotoxic (doxorubicin) treatment. In a mouse model we showed that ectopic overexpression of LMTK3 decreases the efficacy of doxorubicin in reducing tumor growth. Interestingly, breast cancer cells overexpressing LMTK3 delayed the generation of double strand breaks (DSBs) after exposure to doxorubicin, as measured by the formation of γH2AX foci. This effect was at least partly mediated by decreased activity of ataxia-telangiectasia mutated kinase (ATM) as indicated by its reduced phosphorylation levels. In addition, our RNA-seq analyses showed that doxorubicin differentially regulated the expression of over 700 genes depending on LMTK3 protein expression levels. Furthermore, these genes were found to promote DNA repair, cell viability and tumorigenesis processes / pathways in LMTK3-overexpressing MCF7 cells. In human cancers, immunohistochemistry staining of LMTK3 in pre- and postchemotherapy breast tumor pairs from four separate clinical cohorts revealed a significant increase of LMTK3 following both doxorubicin and docetaxel based chemotherapy. In aggregate, our findings show for the first time a contribution of LMTK3 in cytotoxic drug resistance in breast cancer