Search for the ⁷³Gaground-state doublet splitting in the β decay of ⁷³Zn

The existence of two close-lying nuclear states in ⁷³Ga has recently been experimentally determined: a 1/2⁻ spin-parity for the ground state was measured in a laser spectroscopy experiment, while a J_π = 3/2⁻ level was observed in transfer reactions. This scenario is supported by Coulomb excitation studies, which set a limit for the energy splitting of 0.8 keV. In this work, we report on the study of the excited structure of ⁷³Ga populated in the β decay of ⁷³Zn produced at ISOLDE, CERN. Using β-gated, γ-ray singles, and γ –γ coincidences, we have searched for energy differences to try to delimit the ground-state energy splitting, providing a more stringent energy difference limit. Three new half-lives of excited states in ⁷³Ga have been measured using the fast-timing ;method with LaBr₃(Ce) detectors. From our study, we help clarify the excited structure of ⁷³G and we extend the existing ⁷³Zn decay to ⁷³Ga with 8 new energy levels and 35 γ transitions. We observe a 195-keV transition consistent with a γ ray de-exciting a short-lived state in the β-decay parent ⁷³Zn

The mutable nature of particle-core excitations with spin in the one-valence-proton nucleus Sb-133

The gamma-ray decay of excited states of the one-valence-proton nucleus Sb-133 has been studied using cold-neutron induced fission of U-235 and Pu-241 targets, during the EXILL campaign at the ILL reactor in Grenoble. By using a highly efficient HPGe array, coincidences between gamma-rays prompt with the fission event and those delayed up to several tens of microseconds were investigated, allowing to observe, for the first time, high-spin excited states above the 16.6 mu s isomer. Lifetimes analysis, performed by fast-timing techniques with LaBr3(Ce) scintillators, revealed a difference of almost two orders of magnitude in B(M1) strength for transitions between positive-parity medium-spin yrast states. The data are interpreted by a newly developed microscopic model which takes into account couplings between core excitations (both collective and non-collective) of the doubly magic nucleus Sn-132 and the valence proton, using Skyrme effective interaction in a consistent way. The results point to a fast change in the nature of particle-core excitations with increasing spin. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license

Tumorigenic transformation of human prostatic epithelial cell line RWPE-1 by growth hormone-releasing hormone (GHRH)

Background: Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors. In this study, we analyzed the carcinogenetic potential of exposure to GHRH of a nontumor human prostate epithelial cell line (RWPE-1) as well as its transforming effect in a xenograft model. Methods: We performed cell viability, cell proliferation, adhesion and migration assays. In addition, metalloprotease (MMP)-2 activity by means gelatin zymography, GHRH-R subcellular location using confocal immunofluorescence microscopy and vascular endothelial growth factor (VEGF) levels by enzyme-linked immunoassay were assessed. Besides, we developed an in vivo model in order vivo model to determine the role of GHRH on tumorigenic transformation of RWPE-1 cells. Results: In cell cultures, we observed development of a migratory phenotype consistent with the gelatinolytic activity of MMP-2, expression of VEGF, as well as E-cadherin-mediated cell-cell adhesion and increased cell motility. Treatment with 0.1 µM GHRH for 24 h significantly increased cell viability and cell proliferation. Similar effects of GHRH were seen in RWPE-1 tumors developed by subcutaneous injection of GHRH-treated cells in athymic nude mice, 49 days after inoculation. Conclusions: Thus, GHRH appears to act as a cytokine in the transformation of RWPE-1 cells by mechanisms that likely involve epithelial-mesenchymal transition, thus reinforcing the role of GHRH in tumorigenesis of prostate.Universidad de Alcal

Growth hormone-releasing hormone receptor antagonists modify molecular machinery in the progression of prostate cancer

Background: Therapeutic strategies should be designed to transform aggressive prostate cancer phenotypes to a chronic situation. To evaluate the effects of the new growth hormone-releasing hormone receptor (GHRH-R) antagonists: MIA-602, MIA-606, and MIA-690 on processes associated with cancer progression as cell proliferation, adhesion, migration, and angiogenesis. Methods: We used three human prostate cell lines (RWPE-1, LNCaP, and PC3). We analyzed several molecules such as E-cadherin, ?-catenin, Bcl2, Bax, p53, MMP2, MMP9, PCNA, and VEGF and signaling mechanisms that are involved on effects exerted by GHRH-R antagonists. Results: GHRH-R antagonists decreased cell viability and provoked a reduction in proliferation in LNCaP and PC3 cells. Moreover, GHRH-R antagonists caused a time-dependent increase of cell adhesion in all three cell lines and retarded the wound closure with the highest value with MIA-690 in PC3 cells. GHRH-R antagonists also provoked a large number of cells in SubG0 phase revealing an increase in apoptotic cells in PC3 cell line. Conclusions: Taken all together, GHRH-R antagonists of the MIAMI series appear to be inhibitors of tumor progression in prostate cancer and should be considered for use in future therapeutic strategies on this malignancy.Junta de Comunidades de Castilla-La ManchaUniversidad de Alcal

In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma.

Edelfosine is the prototype molecule of a family of anticancer drugs collectively known as synthetic alkyl-lysophospholipids. This drug holds promise as a selective antitumor agent, and a number of preclinical assays are in progress. In this study, we observe the accumulation of edelfosine in brain tissue after its oral administration in Compritol® and Precirol® lipid nanoparticles (LN). The high accumulation of edelfosine in brain was due to the inhibition of P-glycoprotein by Tween® 80, as verified using a P-glycoprotein drug interaction assay. Moreover, these LN were tested in vitro against the C6 glioma cell line, which was later employed to establish an in vivo xenograft mouse model of glioma. In vitro studies revealed that edelfosine-loaded LN induced an antiproliferative effect in C6 glioma cell line. In addition, in vivo oral administration of drug-loaded LN in NMRI nude mice bearing a C6 glioma xenograft tumor induced a highly significant reduction in tumor growth (p<0.01) fourteen days after the beginning of the treatment. Our results showed that Tween® 80 coated Compritol® and Precirol® LN can effectively inhibit the growth of C6 glioma cells in vitro and suggest that edelfosine-loaded LN represent an attractive option for the enhancement of antitumor activity on brain tumors in vivo

Abrupt shape transition at neutron number N=60: B(E2) values in Sr-94,Sr-96,Sr-98 from fast gamma-gamma timing

Lifetimes of low-lying yrast states in neutron-rich Sr-94,Sr-96,Sr-98 have been measured by Germanium-gated gamma-gamma fast timing with LaBr3(Ce) detectors using the EXILL& FATIMA spectrometer at the Institut Laue-Langevin. Sr fission products were generated using cold-neutron-induced fission of 235U and stopped almost instantaneously within the thick target. The experimental B(E2) values are compared with results of Monte Carlo shell-model calculations made without truncation on the occupation numbers of the orbits spanned by eight proton and eight neutron orbits and show good agreement. Similarly to the Zr isotopes, the abrupt shape transition in the Sr isotopes near neutron number N = 60 is identified as being caused by many-proton excitations to its g(9/2) orbit

The standardisation of vernacular architecture: Wine buildings in Andalusia

Production buildings constitute a specific section of vernacular architecture, with distinct characteristics. In Andalusia, within this group, the architecture of wine, acquires an important relevancne, the wine cellars. They are a large number of buildings, which were built in the 18th, and 19th centuries. This happened when traditional Andalusian wine production was transformed into a modern wine industry. An industrial development generated a vast architectural ensemble of unique characteristics. This has been studied especially in the Sherry wine region, but it is also present in other regions such as MontillaMoriles or El Condado de Huelva. The architectural, and industrial wine development in the 19th century was fundamentally based on the repetition of a specific model: the basilica cellar. A simplified formal, and constructive system that comes from the standardisation of the vernacular cellar, and that establishes early points of convergence with the industrial building. A model that continues the tradition in terms of construction, and structure, but conceptually modern in its modular, and repeatable condition. Its reiteration, and extreme simplification made possible the construction of large industrial complexes, and the city transformation. The industrial importance achieved by the wine agro-industry, and the vernacular quality of its architecture introduce different references in Spanish industrial historiograph

Anti-proliferative and pro-apoptotic effects of GHRH antagonists in prostate cancer

Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors. In vitro and in vivo studies have demonstrated that GHRH antagonists inhibit the growth of several cancers. GHRH antagonists, JMR-132 and JV-1-38 inhibit the growth of androgen-independent prostate tumors. Here we investigated the involvement of GHRH antagonists in proliferative and apoptotic processes. We used non-tumoral RWPE-1 and tumoral LNCaP and PC3 human prostatic epithelial cells, as well as an experimental model of human tumor PC3 cells. We evaluated the effects of JMR-132 and JV-1-38 antagonists on cell viability and proliferation in the three cell lines by means of MTT and BrdU assays, respectively, as well as on cell cycle and apoptotic process in PC3 cells. The expression levels of PCNA, p53, p21, CD44, Cyclin D1, c-myc, Bax and Bcl2 were determined in both in vivo and in vitro models by means of Western-blot and RT-PCR. GHRH antagonists suppressed cell proliferation and decreased the levels of the proliferation marker, PCNA, in the three cell lines and in PC3 tumor. GHRH antagonists led to an increase of cells in S-phase and a decrease in G1 and G2/M phases, and induced S-phase arrest and increase of apoptotic cells. The effects of GHRH-antagonists on cell cycle could be due to the changes observed in the expression of p21, p53, Bax, Bcl2, CD44, Cyclin D1, c-myc and caspase 3. Present results confirm and extend the role of GHRH antagonists as anti-proliferative and pro-apoptotic molecules in prostate cancer.Junta de Comunidades de Castilla-La Manch

Decoration of squalenoyl-gemcitabine nanoparticles with squalenyl-hydroxybisphosphonate for the treatment of bone tumors

Therapeutic perspectives of bone tumors such as osteosarcom are main restricted due to the inefficacy of current treatments. We propose here the construction of a novel anticancers qualene-based nanomedicine with bone affinity and retention capacity. A squalenyl-hydroxybisphosphonate molecule was synthetized by chemical conjugation of a 1-hydroxyl-1,1-bi-sphosphonatemoiety to the squalenechain. This amphiphilic compound was inserted onto squalenoyl-gemcitabinenano-particles using the nanoprecipitation method. The co-assemblyled to nanoconstructsof 75 nm, with different morphology and colloidal properties. The presence of squalenyl-hydroxybi-sphosphonate enhanced the nanoparticles binding affinity for hydroxyapatite,a mineral present in the bone. Moreover, the in vitro anticancer activity was preserved when tested in commercial and patient-treated derived pedia tricoste osarcomacells. Furtherin vivo studies will shed lighton the potential of these nano medicines for the treatment of bones arcomas