The SPS as accelerator of Pb82+^{82+} ions

In 1994 the CERN SPS was used for the first time to accelerate fully stripped ions of the Pb208 isotope from the equivalent proton momentum of 13 GeV/c to 400 GeV/c. In the CERN PS, which was used as injector, the lead was accelerated as Pb53+ ions and then fully stripped in the transfer line from PS to SPS. The radio frequency swing which is needed in order to keep the synchronism during acceleration is too big to have the SPS cavities deliver enough voltage for all frequencies. For that reason a new technique of fixed frequency acceleration was used. With this technique up to 70% of the injected beam could be captured and accelerated up to the extraction energy, the equivalent of 2.2 1010 charges. The beam was extracted over a 5 sec. long spill and was then delivered to different experiments at the same time

Is there life after degeneration? The organizational life cycle of cooperatives under a ‘grow-or-die’ dichotomy

This article provides an in-depth, longitudinal analysis combining real-time and retrospective data on a set of Mondragon's industrial cooperatives that are organized as international groups. We examine the life cycle of these international cooperative groups, which is expected to evolve differently to that of small- and medium-sized cooperatives that operate exclusively on a local scale. The article is theoretically informed by the cooperative life cycle theory, as well as by recent insights from the degeneration and regeneration theses. Our analysis yields an intricate picture of the evolution of cooperatives faced with a ‘grow-or-die’ dichotomy. On the one hand, our findings reject the highly simplistic and deterministic view of the degeneration thesis by demonstrating that these cooperatives can mobilize resources to revitalize cooperative values and practices. On the other, we find that regeneration may not occur in a consistent, sequential fashion as the previous literature suggests, but rather degenerative and regenerative tendencies can occur simultaneously, even leading to long-lasting, unresolvable situations. In light of this, the article asks future research to draw on power-aware and politically informed approaches for further understanding of how cooperatives manage the tensions at each organizational stage of their life cycle, and of which organizational actors benefit, and how, from reversing some degenerative tendencies while maintaining others intact

Acceleration of High Intensity Proton Beams

In 1998 the CERN SPS accelerator finished a five years long program providing 450GeV proton beams for neutrino physics. These experiments required the highest possible beam intensity the SPS can deliver. During the last five years the maximum proton intensity in the SPS has steadily been increased to a maximum of 4.8 1013 protons per cycle. In order to achieve these intensities a careful monitoring and improvement of the vertical aperture was necessary. Improved feedback systems on the different RF cavities were needed in order to avoid instabilities. Also the quality (emittance and extraction spill) of the injector, the CERN PS, had be optimised

High intensity proton beams in a multi-cycled SPS

The SPS ran for 247 days during 1994; 64% of this was with high intensity proton beam for physics data taking in the Fixed Target mode of operation, 12% was for a lead run at the end of the year, with the remaining 24% spent in setting up and machine development. The SPS supplied LEP with 8 bunches of electrons and 8 bunches of positrons either in the 14.4 or 19.2 seconds interleaved cycling mode during the operation with protons or lead ions respectively. The new record peak intensity during the year was 3.9x1013 protons per pulse at 450GeV. A total of 11x1018 proton were delivered to all targets, with an overall average during physics of 2.5x1013 protons per pulse at 450GeV. Some 6x1018 protons were delivered to both neutrino experiments

The SPS as lead-ion accelerator

In 1995 the CERN SPS was used during two months to accelerate fully stripped ions of the Pb208 isotope from the equivalent proton momentum of 13 GeV/c to 400 GeV/c. The radio frequency swing which is needed in order to keep the synchronism during acceleration is too big to have the SPS cavities deliver enough voltage for all frequencies. In a first stage, the beam is accelerated from 13 GeV/c to 26 GeV/c using the fixed frequency mode. During this stage the beam is grouped in four 2msec batches, separated by 3msec holes during which the frequency is changed in order to keep synchronism. At 26 GeV the beams are de-bunched and recaptured in order to fill the 3msec holes. From there on the lead ions are then accelerated up to 400 GeV/c with the normal frequency program. The de-bunching and recapture at 26 GeV improved the effective spill at extraction by a factor of three. Intensities up to 3.9 1010 charges could be obtained at 400 GeV/c. The total efficiency of the two RF captures was 64%

Study of the chemotactic response of multicellular spheroids in a microfluidic device

YesWe report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS) was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC–19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC–19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it.This work has been supported by National Research Program of Spain (DPI2011-28262-c04-01) and by the project "MICROANGIOTHECAN" (CIBERBBN, IMIBIC and SEOM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Translog, a web browser for studying the expression divergence of homologous genes

<p>Abstract</p> <p>Background</p> <p>Increasing amount of data from comparative genomics, and newly developed technologies producing accurate gene expression data facilitate the study of the expression divergence of homologous genes. Previous studies have individually highlighted factors that contribute to the expression divergence of duplicate genes, e.g. promoter changes, exon structure heterogeneity, asymmetric histone modifications and genomic neighborhood conservation. However, there is a lack of a tool to integrate multiple factors and visualize their variety among homologous genes in a straightforward way.</p> <p>Results</p> <p>We introduce Translog (a web-based tool for Transcriptome comparison of homologous genes) that assists in the comparison of homologous genes by displaying the loci in three different views: promoter view for studying the sharing/turnover of transcription initiations, exon structure for displaying the exon-intron structure changes, and genomic neighborhood to show the macro-synteny conservation in a larger scale. CAGE data for transcription initiation are mapped for each transcript and can be used to study transcription turnover and expression changes. Alignment anchors between homologous loci can be used to define the precise homologous transcripts. We demonstrate how these views can be used to visualize the changes of homologous genes during evolution, particularly after the 2R and 3R whole genome duplication.</p> <p>Conclusion</p> <p>We have developed a web-based tool for assisting in the transcriptome comparison of homologous genes, facilitating the study of expression divergence.</p

EGFR Kinase Promotes Acquisition of Stem Cell-Like Properties: A Potential Therapeutic Target in Head and Neck Squamous Cell Carcinoma Stem Cells

Members of the EGFR/ErbB family of tyrosine kinases are found to be highly expressed and deregulated in many cancers, including head and neck squamous cell carcinoma (HNSCC). The ErbB family, including EGFR, has been demonstrated to play key roles in metastasis, tumorigenesis, cell proliferation, and drug resistance. Recently, these characteristics have been linked to a small subpopulation of cells classified as cancer stem cells (CSCs) which are believed to be responsible for tumor initiation and maintenance. In this study, we investigated the possible role of EGFR as a regulator of “stemness” in HNSCC cells. Activation of EGFR by the addition of EGF ligand or ectopic expression of EGFR in two established HNSCC cell lines (UMSCC-22B and HN-1) resulted in the induction of CD44, BMI-1, Oct-4, NANOG, CXCR4, and SDF-1. Activation of EGFR also resulted in increased tumorsphere formation, a characteristic ability of cancer stem cells. Conversely, treatment with the EGFR kinase inhibitor, Gefinitib (Iressa), resulted in decreased expression of the aforementioned genes, and loss of tumorsphere-forming ability. Similar trends were observed in a 99.9% CD44 positive stem cell culture derived from a fresh HNSCC tumor, confirming our findings for the cell lines. Additionally, we found that these putative cancer stem cells, when treated with Gefitinib, possessed a lower capacity to invade and became more sensitive to cisplatin-induced death in vitro. These results suggest that EGFR plays critical roles in the survival, maintenance, and function of cancer stem cells. Drugs that target EGFR, perhaps administered in combination with conventional chemotherapy, might be an effective treatment for HNSCC