Working group report on beam plasmas, electronic propulsion, and active experiments using beams

The JPL Workshop addressed a number of plasma issues that bear on advanced spaceborne technology for the years 2000 and beyond. Primary interest was on the permanently manned space station with a focus on identifying environmentally related issues requiring early clarification by spaceborne plasma experimentation. The Beams Working Group focused on environmentally related threats that platform operations could have on the conduct and integrity of spaceborne beam experiments and vice versa. Considerations were to include particle beams and plumes. For purposes of definition it was agreed that the term particle beams described a directed flow of charged or neutral particles allowing single-particle trajectories to represent the characteristics of the beam and its propagation. On the other hand, the word plume was adopted to describe a multidimensional flow (or expansion) of a plasma or neutral gas cloud. Within the framework of these definitions, experiment categories included: (1) Neutral- and charged-particle beam propagation, with considerations extending to high powers and currents. (2) Evolution and dynamics of naturally occurring and man-made plasma and neutral gas clouds. In both categories, scientific interest focused on interactions with the ambient geoplasma and the evolution of particle densities, energy distribution functions, waves, and fields

Effects of growth rate, size, and light availability on tree survival across life stages: a demographic analysis accounting for missing values and small sample sizes.

The data set supporting the results of this article is available in the Dryad repository, http://dx.doi.org/10.5061/dryad.6f4qs. Moustakas, A. and Evans, M. R. (2015) Effects of growth rate, size, and light availability on tree survival across life stages: a demographic analysis accounting for missing values.Plant survival is a key factor in forest dynamics and survival probabilities often vary across life stages. Studies specifically aimed at assessing tree survival are unusual and so data initially designed for other purposes often need to be used; such data are more likely to contain errors than data collected for this specific purpose

Increased fucosylation has a pivotal role in invasive and metastatic properties of head and neck cancer stem cells

Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with high mortality rates. Major challenges for OSCC management include development of resistance to therapy and early formation of distant metastases. Cancer stem cells (CSCs) have emerged as important players in both pathologic mechanisms. Increased fucosylation activity and increased expression of fucosylated polysaccharides, such as Sialyl Lewis X (SLex), are associated with invasion and metastasis. However, the role of fucosylation in CSCs has not been elucidated yet. We used the spheroid culture technique to obtain a CSC-enriched population and compared orospheres with adherent cells. We found that orospheres expressed markers of CSCs and metastasis at higher levels, were more invasive and tumorigenic, and were more resistant to cisplatin/radiation than adherent counterparts. We found fucosyltransferases FUT3 and FUT6 highly up-regulated, increased SLexexpression and increased adhesion by shear flow assays in orospheres. Inhibition of fucosylation negatively affected orospheres formation and invasion of oral CSCs. These results confirm that orospheres are enriched in CSCs and that fucosylation is of paramount importance for CSC invasion. In addition, SLexmay play a key role in CSC metastasis. Thus, inhibition of fucosylation may be used to block CSCs and metastatic spread

Beyond national narratives? : centenary histories, the First World War and the Armenian Genocide

In April 2015 the centenary of the Armenian Genocide was commemorated. Just like the First World War centenary, this anniversary has provoked a flurry of academic and public interest in what remains a highly contested history. This article assesses the state of the current historiography on the fate of the Ottoman Armenians. It focuses on the possibilities for moving beyond the national narratives which continue to dominate the field, in particular through connecting the case of the Armenian Genocide to what has been termed a ‘transnational turn’ in the writing of the history of the First World War

ZEB2 regulates endocrine therapy sensitivity and metastasis in luminal a breast cancer cells through a non-canonical mechanism

PURPOSE: The transcription factors ZEB1 and ZEB2 mediate epithelial-to-mesenchymal transition (EMT) and metastatic progression in numerous malignancies including breast cancer. ZEB1 and ZEB2 drive EMT through transcriptional repression of cell-cell junction proteins and members of the tumor suppressive miR200 family. However, in estrogen receptor positive (ER +) breast cancer, the role of ZEB2 as an independent driver of metastasis has not been fully investigated. METHODS: In the current study, we induced exogenous expression of ZEB2 in ER + MCF-7 and ZR-75-1 breast cancer cell lines and examined EMT gene expression and metastasis using dose-response qRT-PCR, transwell migration assays, proliferation assays with immunofluorescence of Ki-67 staining. We used RNA sequencing to identify pathways and genes affected by ZEB2 overexpression. Finally, we treated ZEB2-overexpressing cells with 17β-estradiol (E2) or ICI 182,780 to evaluate how ZEB2 affects estrogen response. RESULTS: Contrary to expectation, we found that ZEB2 did not increase canonical epithelial nor decrease mesenchymal gene expressions. Furthermore, ZEB2 overexpression did not promote a mesenchymal cell morphology. However, ZEB1 and ZEB2 protein expression induced significant migration of MCF-7 and ZR-75-1 breast cancer cells in vitro and MCF-7 xenograft metastasis in vivo. Transcriptomic (RNA sequencing) pathway analysis revealed alterations in estrogen signaling regulators and pathways, suggesting a role for ZEB2 in endocrine sensitivity in luminal A breast cancer. Expression of ZEB2 was negatively correlated with estrogen receptor complex genes in luminal A patient tumors. Furthermore, treatment with 17β-estradiol (E2) or the estrogen receptor antagonist ICI 182,780 had no effect on growth of ZEB2-overexpressing cells. CONCLUSION: ZEB2 is a multi-functional regulator of drug sensitivity, cell migration, and metastasis in ER + breast cancer and functions through non-canonical mechanisms

The State Socialist Mortality Syndrome

Death rates for working-age men in European state socialist countries deviated from general improvements in survival observed in the rest of Europe during the 20th century. The magnitude of structural labor force changes across countries correlates with lagged increases in death rates for men in the working ages. This pattern is consistent with a hypothesis that hyper-development of heavy industry and stagnation (even contraction) of the service sector created anomic conditions leading to unhealthy lifestyles and self-destructive behavior among men moving from primary-sector to secondary-sector occupations. Occupational contrasts within countries similarly show concentration of rising male death rates among blue collar workers. Collapse of state socialist systems produced rapid corrections in labor force structure after 1990, again correlated with a fading of the state socialist mortality syndrome in following decades

Notch Signaling Regulates Mitochondrial Metabolism and NF-κB Activity in Triple-Negative Breast Cancer Cells via IKKα-Dependent Non-canonical Pathways

Triple negative breast cancer (TNBC) patients have high risk of recurrence and metastasis, and current treatment options remain limited. Cancer stem-like cells (CSCs) have been linked to cancer initiation, progression and chemotherapy resistance. Notch signaling is a key pathway regulating TNBC CSC survival. Treatment of TNBC with PI3K or mTORC1/2 inhibitors results in drug-resistant, Notch-dependent CSC. However, downstream mechanisms and potentially druggable Notch effectors in TNBC CSCs are largely unknown. We studied the role of the AKT pathway and mitochondrial metabolism downstream of Notch signaling in TNBC CSC from cell lines representative of different TNBC molecular subtypes as well as a novel patient-derived model. We demonstrate that exposure of TNBC cells to recombinant Notch ligand Jagged1 leads to rapid AKT phosphorylation in a Notch1-dependent but RBP-Jκ independent fashion. This requires mTOR and IKKα. Jagged1 also stimulates mitochondrial respiration and fermentation in an AKT- and IKK-dependent fashion. Notch1 co-localizes with mitochondria in TNBC cells. Pharmacological inhibition of Notch cleavage by gamma secretase inhibitor PF-03084014 in combination with AKT inhibitor MK-2206 or IKK-targeted NF-κB inhibitor Bay11-7082 blocks secondary mammosphere formation from sorted CD90hi or CD44+CD24low (CSCs) cells. A TNBC patient-derived model gave comparable results. Besides mitochondrial oxidative metabolism, Jagged1 also triggers nuclear, NF-κB-dependent transcription of anti-apoptotic gene cIAP-2. This requires recruitment of Notch1, IKKα and NF-κB to the cIAP-2 promoter. Our observations support a model where Jagged1 triggers IKKα-dependent, mitochondrial and nuclear Notch1 signals that stimulate AKT phosphorylation, oxidative metabolism and transcription of survival genes in PTEN wild-type TNBC cells. These data suggest that combination treatments targeting the intersection of the Notch, AKT and NF-κB pathways have potential therapeutic applications against CSCs in TNBC cases with Notch1 and wild-type PTEN expression

NEK5 activity regulates the mesenchymal and migratory phenotype in breast cancer cells

Purpose Breast cancer remains a prominent global disease affecting women worldwide despite the emergence of novel therapeutic regimens. Metastasis is responsible for most cancer-related deaths, and acquisition of a mesenchymal and migratory cancer cell phenotypes contributes to this devastating disease. The utilization of kinase targets in drug discovery have revolutionized the field of cancer research but despite impressive advancements in kinase-targeting drugs, a large portion of the human kinome remains understudied in cancer. NEK5, a member of the Never-in-mitosis kinase family, is an example of such an understudied kinase. Here, we characterized the function of NEK5 in breast cancer. Methods Stably overexpressing NEK5 cell lines (MCF7) and shRNA knockdown cell lines (MDA-MB-231, TU-BcX-4IC) were utilized. Cell morphology changes were evaluated using immunofluorescence and quantification of cytoskeletal components. Cell proliferation was assessed by Ki-67 staining and transwell migration assays tested cell migration capabilities. In vivo experiments with murine models were necessary to demonstrate NEK5 function in breast cancer tumor growth and metastasis. Results NEK5 activation altered breast cancer cell morphology and promoted cell migration independent of effects on cell proliferation. NEK5 overexpression or knockdown does not alter tumor growth kinetics but promotes or suppresses metastatic potential in a cell type-specific manner, respectively. Conclusion While NEK5 activity modulated cytoskeletal changes and cell motility, NEK5 activity affected cell seeding capabilities but not metastatic colonization or proliferation in vivo. Here we characterized NEK5 function in breast cancer systems and we implicate NEK5 in regulating specific steps of metastatic progression