493 research outputs found
Coaxial inverted geometry transistor having buried emitter
The invention relates to an inverted geometry transistor wherein the emitter is buried within the substrate. The transistor can be fabricated as a part of a monolithic integrated circuit and is particularly suited for use in applications where it is desired to employ low actuating voltages. The transistor may employ the same doping levels in the collector and emitter, so these connections can be reversed
Centrosome loss results in an unstable genome and malignant prostate tumors
Localized, nonindolent prostate cancer (PCa) is characterized by large-scale genomic rearrangements, aneuploidy, chromothripsis, and other forms of chromosomal instability (CIN), yet how this occurs remains unclear. A well-established mechanism of CIN is the overproduction of centrosomes, which promotes tumorigenesis in various mouse models. Therefore, we developed a single-cell assay for quantifying centrosomes in human prostate tissue. Surprisingly, centrosome loss-which has not been described in human cancer-was associated with PCa progression. By chemically or genetically inducing centrosome loss in nontumorigenic prostate epithelial cells, mitotic errors ensued, producing aneuploid, and multinucleated cells. Strikingly, transient or chronic centrosome loss transformed prostate epithelial cells, which produced highly proliferative and poorly differentiated malignant tumors in mice. Our findings suggest that centrosome loss could create a cellular crisis with oncogenic potential in prostate epithelial cells.6 month embargo; published online: 2 September 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
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A method of quantifying centrosomes at the single-cell level in human normal and cancer tissue
Centrosome abnormalities are emerging hallmarks of cancer. The overproduction of centrosomes (known as centrosome amplification) has been reported in a variety of cancers and is currently being explored as a promising target for therapy. However, to understand different types of centrosome abnormalities and their impact on centrosome function during tumor progression, as well as to identify tumor subtypes that would respond to the targeting of a centrosome abnormality, a reliable method for accurately quantifying centrosomes in human tissue samples is needed. Here, we established a method of quantifying centrosomes at a single-cell level in different types of human tissue samples. We tested multiple anti-centriole and pericentriolar-material antibodies to identify bona fide centrosomes and multiplexed these with cell border markers to identify individual cells within the tissue. High-resolution microscopy was used to generate multiple Z-section images, allowing us to acquire whole cell volumes in which to scan for centrosomes. The normal cells within the tissue serve as internal positive controls. Our method provides a simple, accurate way to distinguish alterations in centrosome numbers at the level of single cells.National Cancer Institute (NCI) [P30CA23074]; Department of Defense Prostate Cancer Research Program [W81XWH-14-2-0182, W81XWH-14-2-0183, W81XWH-14-2-0185, W81XWH-14-2-0186, W81XWH-15-2-0062]; National Institutes of Health (NIH) [R01GM110166, R01GM126035]; NIH-NCI [RO1CA159406]; Tim and Diane Bowden Cancer Biology Research FellowshipThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
New Constraint on Open Cold-Dark-Matter Models
We calculate the large-angle cross-correlation between the
cosmic-microwave-background (CMB) temperature and the x-ray-background (XRB)
intensity expected in an open Universe with cold dark matter (CDM) and a nearly
scale-invariant spectrum of adiabatic density perturbations. Results are
presented as a function of the nonrelativistic-matter density (in
units of the critical density) and the x-ray bias (evaluated at a
redshift in evolving-bias models) for both an open Universe and a
flat cosmological-constant Universe. Recent experimental upper limits to the
amplitude of this cross-correlation provide a new constraint to the
- parameter space that open-CDM models (and the open-inflation
models that produce them) must satisfy.Comment: 4 pages, LaTeX. Revised version contains additional figure that
clarifies new constraint. (To appear in PRL.
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Integrin α6ÎČ4E variant is associated with actin and CD9 structures and modifies the biophysical properties of cell-cell and cell-extracellular matrix interactions
Integrin alpha 6 beta 4 is an essential, dynamic adhesion receptor for laminin 332 found on epithelial cells, required for formation of strong cell-extracellular matrix (ECM) adhesion and induced migration, and coordinated by regions of the beta 4C cytoplasmic domain. beta 4E, a unique splice variant of beta 4 expressed in normal tissue, contains a cytoplasmic domain of 231 amino acids with a unique sequence of 114 amino acids instead of beta 4C's canonical 1089 amino acids. We determined the distribution of alpha 6 beta 4E within normal human glandular epithelium and its regulation and effect on cellular biophysical properties. Canonical alpha 6 beta 4C expressed in all basal cells, as expected, while alpha 6 beta 4E expressed within a subset of luminal cells. alpha 6 beta 4E expression was induced by three-dimensional culture conditions, activated Src, was reversible, and was stabilized by bortezomib, a proteasome inhibitor. alpha 6 beta 4C expressed in all cells during induced migration, whereas alpha 6 beta 4E was restricted to a subset of cells with increased kinetics of cell-cell and cell-ECM resistance properties. Interestingly, alpha 6 beta 4E presented in "ringlike" patterns measuring similar to 1.75 x 0.72 microns and containing actin and CD9 at cell-ECM locations. In contrast, alpha 6 beta 4C expressed only within hemidesmosome-like structures containing BP180. Integrin alpha 6 beta 4E is an inducible adhesion isoform in normal epithelial cells that can alter biophysical properties of cell-cell and cell-ECM interactions.National Institutes of Health, National Cancer Institute (NIH-NCI) [RO1CA159406]; NIH-NCI [T32CA009213]; NIH, National Heart, Lung, and Blood Institute [P01 HL126609]; Tim and Diane Bowden Fellowship in Cancer Biology; [P30 CA23074]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
A 'Performative' Social Movement: The Emergence of Collective Contentions within Collaborative Governance
The enmeshment of urban movements in networks of collaborative governance has been characterised as a process of co-option in which previously disruptive contentions are absorbed by regimes and reproduced in ways that do not threaten the stability of power relations. Applying a theoretical framework drawn from feminist philosopher Judith Butler this paper directs attention to the development of collective oppositional identities that remain embedded in conventional political processes. In a case study of the English tenants' movement, it investigates the potential of regulatory discourses that draw on market theories of performative voice to offer the collectivising narratives and belief in change that can generate the emotional identification of a social movement. The paper originates the concept of the âperformative social movementâ to denote the contentious claims that continue to emerge from urban movements that otherwise appear quiescent
Analysis of the RC catalog sample in the region overlapping with the regions of the FIRST and SDSS surveys: I. Identification of sources with the VLSS, TXS, NVSS, FIRST, and GB6 catalogs
Radio sources of the RC catalog produced in 1980--1985 at RATAN-600 radio
telescope based on a deep survey of a sky strip centered on the declination of
the SS 433 source are optically identified in the region overlapping with FIRST
and SDSS surveys (about 132 square degrees). The NVSS catalog was used as the
reference catalog for refining the coordinates of the radio sources. The
morphology is found for about 75% of the objects of the sample and the ratio of
single, double and multicomponent radio sources is computed based on FIRST
radio maps. The 74, 365, 1400, and 4850 MHz data of the VLSS, TXS, NVSS, FIRST,
and GB6 catalogs are used to analyze the shape of the spectra.Comment: 16 pages, 3 figure
Phenotype plasticity and altered sensitivity to chemotherapeutic agents in aggressive prostate cancer cells
In 2023, approximately 288,300 new diagnoses of prostate cancer will occur, with 34,700 disease-related deaths. Death from prostate cancer is associated with metastasis, enabled by progression of tumor phenotypes and successful extracapsular extension to reach Batsonâs venous plexus, a specific route to the spine and brain. Using a mouse-human tumor xenograft model, we isolated an aggressive muscle invasive cell population of prostate cancer, called DU145J7 with a distinct biophysical phenotype, elevated histone H3K27, and increased matrix metalloproteinase 14 expression as compared to the non-aggressive parent cell population called DU145WT. Our goal was to determine the sensitivities to known chemotherapeutic agents of the aggressive cells as compared to the parent population. High-throughput screening was performed with 5,578 compounds, comprising of approved and investigational drugs for oncology. Eleven compounds were selected for additional testing, which revealed that vorinostat, 5-azacitidine, and fimepinostat (epigenetic inhibitors) showed 2.6-to-7.5-fold increases in lethality for the aggressive prostate cancer cell population as compared to the parent, as judged by the concentration of drug to inhibit 50% cell growth (IC50). On the other hand, the DU145J7 cells were 2.2-to-4.0-fold resistant to mitoxantrone, daunorubicin, and gimatecan (topoisomerase inhibitors) as compared to DU145WT. No differences in sensitivities between cell populations were found for docetaxel or pirarubicin. The increased sensitivity of DU145J7 prostate cancer cells to chromatin modifying agents suggests a therapeutic vulnerability occurs after tumor cells invade into and through muscle. Future work will determine which epigenetic modifiers and what combinations will be most effective to eradicate early aggressive tumor populations
Developing argumentation skills in mathematics through computer-supported collaborative learning: the role of transactivity
Collaboration scripts and heuristic worked examples are effective means to scaffold university freshmenâs mathematical argumentation skills. Yet, which collaborative learning processes are responsible for these effects has remained unclear. Learners presumably will gain the most out of collaboration if the collaborators refer to each otherâs contributions in a dialectic way (dialectic transactivity). Learners also may refer to each otherâs contributions in a dialogic way (dialogic transactivity). Alternatively, learners may not refer to each otherâs contributions at all, but still construct knowledge (constructive activities). This article investigates the extent to which constructive activities, dialogic transactivity, and dialectic transactivity generated by either the learner or the learning partner can explain the positive effects of collaboration scripts and heuristic worked examples on the learnersâ disposition to use argumentation skills. We conducted a 2 Ă 2 experiment with the factors collaboration script and heuristic worked examples with N = 101 math teacher students. Results showed that the learnersâ engagement in self-generated dialectic transactivity (i.e., responding to the learning partnerâs contribution in an argumentative way by critiquing and/or integrating their learning partnerâs contributions) mediated the effects of both scaffolds on their disposition to use argumentation skills, whereas partner-generated dialectic transactivity or any other measured collaborative learning activity did not. To support the disposition to use argumentation skills in mathematics, learning environments should thus be designed in a way to help learners display dialectic transactivity. Future research should investigate how learners might better benefit from the dialectic transactivity generated by their learning partners
Multilevel analysis in CSCL Research
Janssen, J., Erkens, G., Kirschner, P. A., & Kanselaar, G. (2011). Multilevel analysis in CSCL research. In S. Puntambekar, G. Erkens, & C. Hmelo-Silver (Eds.), Analyzing interactions in CSCL: Methods, approaches and issues (pp. 187-205). New York: Springer. doi:10.1007/978-1-4419-7710-6_9CSCL researchers are often interested in the processes that unfold between learners in online learning environments and the outcomes that stem from these interactions. However, studying collaborative learning processes is not an easy task. Researchers have to make quite a few methodological decisions such as how to study the collaborative process itself (e.g., develop a coding scheme or a questionnaire), on the appropriate unit of analysis (e.g., the individual or the group), and which statistical technique to use (e.g., descriptive statistics, analysis of variance, correlation analysis). Recently, several researchers have turned to multilevel analysis (MLA) to answer their research questions (e.g., Cress, 2008; De Wever, Van Keer, Schellens, & Valcke, 2007; Dewiyanti, Brand-Gruwel, Jochems, & Broers, 2007; Schellens, Van Keer, & Valcke, 2005; Strijbos, Martens, Jochems, & Broers, 2004; Stylianou-Georgiou, Papanastasiou, & Puntambekar, chapter #). However, CSCL studies that apply MLA analysis still remain relatively scarce. Instead, many CSCL researchers continue to use âtraditionalâ statistical techniques (e.g., analysis of variance, regression analysis), although these techniques may not be appropriate for what is being studied. An important aim of this chapter is therefore to explain why MLA is often necessary to correctly answer the questions CSCL researchers address. Furthermore, we wish to highlight the consequences of failing to use MLA when this is called for, using data from our own studies
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