Laser cleaning of diagnostic mirrors from tungsten-oxygen tokamak-like contaminants

This paper presents a laboratory-scale experimental investigation about the laser cleaning of diagnostic first mirrors from tokamak-like contaminants, made of oxidized tungsten compounds with different properties and morphology. The re-deposition of contaminants sputtered from a tokamak first wall onto first mirrors' surfaces could dramatically decrease their reflectivity in an unacceptable way for the proper functioning of plasma diagnostic systems. The laser cleaning technique has been proposed as a solution to tackle this issue. In this work, pulsed laser deposition was exploited to produce rhodium films functional as first mirrors and to deposit onto them contaminants designed to be realistic in reproducing materials expected to be re-deposited on first mirrors in a tokamak environment. The same laser system was also used to perform laser cleaning experiments, exploiting a sample handling procedure that allows one to clean some cm2 in a few minutes. Cleaning effectiveness was evaluated in terms of specular reflectance recovery and mirror surface integrity. The effect of different laser wavelengths (λ= 1064, 266 nm) on the cleaning process was also addressed, as well as the impact of multiple contamination/cleaning cycles on the process outcome. A satisfactory recovery of pristine mirror reflectance (≥90%) was obtained in the vis-NIR spectral range, avoiding at the same time mirror damaging. The results here presented show the potential of the laser cleaning technique as an attractive solution for the cleaning of diagnostic first mirrors

Ultra-intense laser interaction with nanostructured near-critical plasmas

Near-critical plasmas irradiated at ultra-high laser intensities (I > 1018W/cm2) allow to improve the performances of laser-driven particle and radiation sources and to explore scenarios of great astrophysical interest. Near-critical plasmas with controlled properties can be obtained with nanostructured low-density materials. By means of 3D Particle-In-Cell simulations, we investigate how realistic nanostructures influence the interaction of an ultra-intense laser with a plasma having a near-critical average electron density. We find that the presence of a nanostructure strongly reduces the effect of pulse polarization and enhances the energy absorbed by the ion population, while generally leading to a significant decrease of the electron temperature with respect to a homogeneous near-critical plasma. We also observe an effect of the nanostructure morphology. These results are relevant both for a fundamental understanding and for the foreseen applications of laser-plasma interaction in the near-critical regime

In situ cleaning of diagnostic first mirrors: An experimental comparison between plasma and laser cleaning in ITER-relevant conditions

This paper presents an experimental comparison between the plasma cleaning and the laser cleaning techniques of diagnostic first mirrors (FMs). The re-deposition of contaminants sputtered from a tokamak first wall onto FMs could dramatically decrease their reflectance in an unacceptable way for the proper functioning of plasma diagnostic systems. Therefore, suitable in situ cleaning solutions will be required to recover the FMs reflectance in ITER. Currently, plasma cleaning and laser cleaning are considered the most promising solutions. In this work, a set of ITER-like rhodium mirrors contaminated with materials tailored to reproduce tokamak redeposits is employed to experimentally compare plasma and laser cleaning against different criteria (reflectance recovery, mirror integrity, time requirement). We show that the two techniques present different complementary features that can be exploited for the cleaning of ITER FMs. In particular, plasma cleaning ensures an excellent reflectance recovery in the case of compact contaminants, while laser cleaning is faster, gentler, and more effective in the case of porous contaminant. In addition, we demonstrate the potential benefits of a synergistic solution which combines plasma and laser cleaning to exploit the best features of each technique

Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore–microtubule attachments

Accurate chromosome segregation during mitosis relies on a dynamic kinetochore (KT)–microtubule (MT) interface that switches from a labile to a stable condition in response to correct MT attachments. This transition is essential to satisfy the spindle-assembly checkpoint (SAC) and couple MT-generated force with chromosome movements, but the underlying regulatory mechanism remains unclear. In this study, we show that during mitosis the MT- and KT-associated protein CLASP2 is progressively and distinctively phosphorylated by Cdk1 and Plk1 kinases, concomitant with the establishment of KT–MT attachments. CLASP2 S1234 was phosphorylated by Cdk1, which primed CLASP2 for association with Plk1. Plk1 recruitment to KTs was enhanced by CLASP2 phosphorylation on S1234. This was specifically required to stabilize KT–MT attachments important for chromosome alignment and to coordinate KT and non-KT MT dynamics necessary to maintain spindle bipolarity. CLASP2 C-terminal phosphorylation by Plk1 was also required for chromosome alignment and timely satisfaction of the SAC. We propose that Cdk1 and Plk1 mediate a fine CLASP2 “phospho-switch” that temporally regulates KT–MT attachment stability.National Institutes of Health (U.S.) (NIH/National Institute of General Medical Sciences grant GM088313)National Institutes of Health (U.S.) (NIH grant 5R01-GM078373)American Heart Association (grant-in-aid 10GRNT4230026)National Institutes of Health (U.S.) (NIH grant GM51542)Fundação para a Ciência e a Tecnologia (FCT grant REEQ/564/BIO/2005 (EU-FEDER), POCI 2010

p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer

Background: Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer. Patients and methods: Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients. Results: p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2. Conclusions: We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cance

The Microenvironment Determines the Breast Cancer Cells' Phenotype: Organization of MCF7 Cells in 3D Cultures

Background: Stromal-epithelial interactions mediate breast development, and the initiation and progression of breast cancer. In the present study, we developed 3-dimensional (3D) in vitro models to study breast cancer tissue organization and the role of the microenvironment in phenotypic determination. Methods: The human breast cancer MCF7 cells were grown alone or co-cultured with primary human breast fibroblasts. Cells were embedded in matrices containing either type I collagen or a combination of reconstituted basement membrane proteins and type I collagen. The cultures were carried out for up to 6 weeks. For every time point (1-6 weeks), the gels were fixed and processed for histology, and whole-mounted for confocal microscopy evaluation. The epithelial structures were characterized utilizing immunohistochemical techniques; their area and proliferation index were measured using computerized morphometric analysis. Statistical differences between groups were analyzed by ANOVA, Dunnett's T3 post-hoc test and chi-square. Results: Most of the MCF7 cells grown alone within a collagen matrix died during the first two weeks; those that survived organized into large, round and solid clusters. The presence of fibroblasts in collagen gels reduced MCF7 cell death, induced cell polarity, and the formation of round and elongated epithelial structures containing a lumen. The addition of reconstituted basement membrane to collagen gels by itself had also survival and organizational effects on the MCF7 cells. Regardless of the presence of fibroblasts, the MCF7 cells both polarized and formed a lumen. The addition of fibroblasts to the gel containing reconstituted basement membrane and collagen induced the formation of elongated structures. Conclusions: Our results indicate that a matrix containing both type I collagen and reconstituted basement membrane, and the presence of normal breast fibroblasts constitute the minimal permissive microenvironment to induce near-complete tumor phenotype reversion. These human breast 3D tissue morphogenesis models promise to become reliable tools for studying tissue interactions, therapeutic screening and drug target validation

DEL ESPACIO DESHUMANIZADO AL ESPACIO DE LA MEMORIA: TRAYECTORIAS DE LOS POETAS DEL VEINTISIETE

This work was born as an attempt to answer the following questions: what happens to the members of a literary generation when this generation\u2019s time is over? Do they stray on their own personal path or do they maintain some consistent bonds that witness the road they have walked together? In order to answer these questions we analysed some of the works by D\ue1maso Alonso, Vicente Aleixandre and Luis Cernuda, focusing on some key moments of their production, in particular: the phase of the \u201cpoes\ueda pura\u201d, surrealism, exile and memory. This chronological approach allowed us, on one hand, to shed new light on long-acquired critical evaluations \u2013especially regarding the earlier works of these poets\u2013; and, on the other hand, to pinpoint how, despite the distance that grew between some of them in their life experiences, these authors still shared a common sensibility, which led them to develop similar answers to similar problems. This analysis was performed with special attention to the element of space. In fact, since the introduction of the concept of chronotope by Bakhtin, space and time have become useful categories for the analysis of literary works; yet, traditionally, they have been associated most frequently with prose. For this reason, the analysis of the poetical space is a kind of novelty, which provides an exceptional point of observation on texts, offering, with contributions from linguistics and traditional critical studies, new readings of classical works. This way, a correspondence can be established between the changes the concept of space itself experiments in these authors and the evolution of their poetical world. We start from the artificial, claustrophobic space that is typical of the \u201cpoes\ueda pura\u201d, where the young poet keeps a separate stance from the outside world, lingering in his room in strict meditation, only to later assist to its definitive breakthrough, when the chaotic agglomerate of irrational objects floating into nothingness, which is the trademark of the surrealist period, takes over. Afterwards, the painful occurrence of the exile, experienced both inside and outside the Spanish peninsula, contributes in transforming again the concept of space, pointing out a severe division of its physical environment, which is somehow mended by resorting to a partly-metaphysical, partly-psychological reconstruction. The last modification of this poetical chronotope, induced by the increasing proximity of the end of these poets\u2019 lives, is represented by a further dwelling on the idea of limit, both from a temporal and spatial point of view, which puts in peril the same possibility of writing poetry. The risk of this poetical aporia is finally eluded by Aleixandre\u2019s appeal to dialogue, which doubles the space available, allowing a new configuration that comprises, in the counterpoint of two poetical voices, the finite and the infinite aspects of reality. Thanks to this achievement, we can answer affirmatively to our initial question, and thus recognize in Aleixandre the point of equilibrium of this complex triangle of friendship and jealousy, where the emulation and the desire to surpass the other shaped marvellous spaces of poetical beauty

Laser-driven production with advanced targets of Copper-64 for medical applications

Radionuclides are of paramount importance in nuclear medicine both for clinical uses and radiopharmaceutical production. Among the others, nuclides suitable for theranostics like Copper-64 are particularly attractive since they can play both a diagnostic and therapeutic role. In the last years, the growing demand for these nuclides stimulated the research of new solutions, along with cyclotrons already in use, for their production. In this respect, a promising alternative is laser-driven proton accelerators based on the interaction of superintense laser pulses with target materials. Because of their potential compactness and flexibility, they are under investigation for several applications ranging from materials science to nuclear medicine. Moreover, the use of advanced Double-Layer targets (DLTs) was identified as a viable route to increase the number and energy of the accelerated protons to satisfy the requirements of demanding applications. In this contribution, we numerically investigate the use of DLT-based laser-driven sources for Copper-64 production. We show that activities relevant to pre-clinical studies can be achieved with an existing 150 TW laser and DLTs. Moreover, we extend the discussion by considering a broad range of laser systems by exploiting a theoretical model. Our results can guide the choice of laser and target parameters for future experimental investigations