186 research outputs found

    The origin and propagation of VVH primary cosmic ray particles

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    Several source spectra were constructed from combinations of 4- and s-process nuclei to match the observed charge spectrum of VVH particles. Their propagation was then followed, allowing for interactions and decay, and comparisons were made between the calculated near-earth spectra and those observed during high altitude balloon flights. None of the models gave good agreement with observations

    Primary cosmic ray particles with z 35 (VVH particles)

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    Large areas of nuclear emulsions and plastic detectors were exposed to the primary cosmic radiation during high altitude balloon flights. From the analysis of 141 particle tracks recorded during a total exposure of 1.3 x 10 to the 7th power sq m ster.sec., a charge spectrum of the VVH particles has been derived

    The effect of collaboration and IT competency on reverse logistics competency - Evidence from Brazilian supply chain executives

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    Business models have being designed, worldwide, to create sustainability competencies and in particular to incorporate reverse logistics, but Brazilian executives have not yet fully adhered to Law 12,305 on solid waste and reverse logistics. What would be the Brazilian executives' perception about reverse logistics competency and the support provided by a collaborative and IT competency? The objective of the paper is to investigate the effects of collaboration and IT competency in developing reverse logistics competency, as a strategy, and its consequences in economic and environmental performance. A survey was performed with 320 Brazilian supply chain executives and analyzed using Structural Equation Modeling. The models demonstrated that collaboration has a direct positive influence on the development of reverse logistics competency, by executives' point of view. The moderation effect between collaboration and IT competency for reverse logistics was not confirmed, since it was adopted a strategic view of reverse logistics. Therefore, despite there was not a moderation effect, IT presented a lower direct effect on reverse logistics competency. Results reinforce that organizations that develop reverse logistics competency tend to improve their economic and environmental performances.info:eu-repo/semantics/publishedVersio

    The Response of Ionization Chambers to Relativistic Heavy Nuclei

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    As part of a recent calibration at the LBL Bevalac for the Heavy Nuclei Experiment on HEAO-3, we have compared the response of a set of laboratory ionization chambers to beams of _(26)Fe, _(36)Kr, _(54)Xe, _(67)Ho, and _(79)Au nuclei at maximum energies ranging from 1666 MeV/amu for Fe to 1049 MeV /amu for Au. The response of these chambers shows a significant deviation from the expected energy dependence, but only a slight deviation from Z^2 scaling

    CD44+CD24− prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis

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    Recent evidence supports the hypothesis that cancer stem cells are responsible for tumour initiation and formation. Using flow cytometry, we isolated a population of CD44+CD24− prostate cells that display stem cell characteristics as well as gene expression patterns that predict overall survival in prostate cancer patients. CD44+CD24− cells form colonies in soft agar and form tumours in NOD/SCID mice when as few as 100 cells are injected. Furthermore, CD44+CD24− cells express genes known to be important in stem cell maintenance, such as BMI-1 and Oct-3/4. Moreover, we can maintain CD44+CD24− prostate stem-like cells as nonadherent spheres in serum-replacement media without substantially shifting gene expression. Addition of serum results in adherence to plastic and shifts gene expression patterns to resemble the differentiated parental cells. Thus, we propose that CD44+CD24− prostate cells are stem-like cells responsible for tumour initiation and we provide a genomic definition of these cells and the differentiated cells they give rise to. Furthermore, gene expression patterns of CD44+CD24− cells have a genomic signature that is predictive of poor patient prognosis. Therefore, CD44+CD24− LNCaP prostate cells offer an attractive model system to both explore the biology important to the maintenance and differentiation of prostate cancer stem cells as well as to develop the therapeutics, as the gene expression pattern in these cells is consistent with poor survival in prostate cancer patients

    CD24 Is Not Required for Tumor Initiation and Growth in Murine Breast and Prostate Cancer Models

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    CD24 is a small, heavily glycosylated, GPI-linked membrane protein, whose expression has been associated with the tumorigenesis and progression of several types of cancer. Here, we studied the expression of CD24 in tumors of MMTV-PyMT, Apc1572/T+ and TRAMP genetic mouse models that spontaneously develop mammary or prostate carcinoma, respectively. We found that CD24 is expressed during tumor development in all three models. In MMTV-PyMT and Apc1572T/+ breast tumors, CD24 was strongly but heterogeneously expressed during early tumorigenesis, but decreased in more advanced stages, and accordingly was increased in poorly differentiated lesions compared with well differentiated lesions. In prostate tumors developing in TRAMP mice, CD24 expression was strong within hyperplastic lesions in comparison with non-hyperplastic regions, and heterogeneous CD24 expression was maintained in advanced prostate carcinomas. To investigate whether CD24 plays a functional role in tumorigenesis in these models, we crossed CD24 deficient mice with MMTV-PyMT, Apc1572T/+ and TRAMP mice, and assessed the influence of CD24 deficiency on tumor onset and tumor burden. We found that mice negative or positive for CD24 did not significantly differ in terms of tumor initiation and burden in the genetic tumor models tested, with the exception of Apc1572T/+ mice, in which lack of CD24 reduced the mammary tumor burden slightly but significantly. Together, our data suggest that while CD24 is distinctively expressed during the early development of murine mammary and prostate tumors, it is not essential for the formation of tumors developing in MMTV-PyMT, Apc1572T/+ and TRAMP mice

    Protocol for Nearly Full-Length Sequencing of HIV-1 RNA from Plasma

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    Nearly full-length genome sequencing of HIV-1 using peripheral blood mononuclear cells (PBMC) DNA as a template for PCR is now a relatively routine laboratory procedure. However, this has not been the case when using virion RNA as the template and this has made full genome analysis of circulating viruses difficult. Therefore, a well-developed procedure for sequencing of full-length HIV-1 RNA directly from plasma was needed. Plasma from U.S. donors representing a range of viral loads (VL) was used to develop the assay. RNA was extracted from plasma and reverse-transcribed. Two or three overlapping regions were PCR amplified to cover the entire viral genome and sequenced for verification. The success of the procedure was sensitive to VL but was routinely successful for VL greater than 105 and the rate declined in proportion to the VL. While the two-amplicon strategy had an advantage of increasing the possibility of amplifying a single species of HIV-1, the three-amplicon strategy was more successful in amplifying samples with low viral loads. This protocol provides a useful tool for molecular analysis to understand the HIV epidemic and pathogenesis, as well as diagnosis, therapy and future vaccine strategies

    DNA repair: the culprit for tumor-initiating cell survival?

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    The existence of “tumor-initiating cells” (TICs) has been a topic of heated debate for the last few years within the field of cancer biology. Their continuous characterization in a variety of solid tumors has led to an abundance of evidence supporting their existence. TICs are believed to be responsible for resistance against conventional treatment regimes of chemotherapy and radiation, ultimately leading to metastasis and patient demise. This review summarizes DNA repair mechanism(s) and their role in the maintenance and regulation of stem cells. There is evidence supporting the hypothesis that TICs, similar to embryonic stem (ES) cells and hematopoietic stem cells (HSCs), display an increase in their ability to survive genotoxic stress and injury. Mechanistically, the ability of ES cells, HSCs and TICs to survive under stressful conditions can be attributed to an increase in the efficiency at which these cells undergo DNA repair. Furthermore, the data presented in this review summarize the results found by our lab and others demonstrating that TICs have an increase in their genomic stability, which can allow for TIC survival under conditions such as anticancer treatments, while the bulk population of tumor cells dies. We believe that these data will greatly impact the development and design of future therapies being engineered to target and eradicate this highly aggressive cancer cell population

    Epithelial to Mesenchymal Transition Is Mechanistically Linked with Stem Cell Signatures in Prostate Cancer Cells

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    Current management of patients diagnosed with prostate cancer (PCa) is very effective; however, tumor recurrence with Castrate Resistant Prostate Cancer (CRPC) and subsequent metastasis lead to poor survival outcome, suggesting that there is a dire need for novel mechanistic understanding of tumor recurrence, which would be critical for designing novel therapies. The recurrence and the metastasis of PCa are tightly linked with the biology of prostate cancer stem cells or cancer-initiating cells that is reminiscent of the acquisition of Epithelial to Mesenchymal Transition (EMT) phenotype. Increasing evidence suggests that EMT-type cells share many biological characteristics with cancer stem-like cells.In this study, we found that PCa cells with EMT phenotype displayed stem-like cell features characterized by increased expression of Sox2, Nanog, Oct4, Lin28B and/or Notch1, consistent with enhanced clonogenic and sphere (prostasphere)-forming ability and tumorigenecity in mice, which was associated with decreased expression of miR-200 and/or let-7 family. Reversal of EMT by re-expression of miR-200 inhibited prostasphere-forming ability of EMT-type cells and reduced the expression of Notch1 and Lin28B. Down-regulation of Lin28B increased let-7 expression, which was consistent with repressed self-renewal capability.These results suggest that miR-200 played a pivotal role in linking the characteristics of cancer stem-like cells with EMT-like cell signatures in PCa. Selective elimination of cancer stem-like cells by reversing the EMT phenotype to Mesenchymal-Epithelial Transition (MET) phenotype using novel agents would be useful for the prevention of tumor recurrence especially by eliminating those cells that are the "Root Cause" of tumor development and recurrence
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