JNK2 inhibits luminal cell commitment in normal mammary glands and tumors

textBreast cancer is a heterogeneous disease with vastly different tumor progression kinetics and survival outcomes depending upon the differentiation state and gene expression patterns of the tumor. Effective treatments exist for patients with endocrine therapy sensitive or HER2 overexpressing tumors, but targeted treatments are not available for other tumor types. The mechanisms governing mammary tumor phenotype generation could prove critical to finding treatments. The c-Jun N-terminal kinase (JNK) pathway has recently been implicated in the inhibition of breast tumor luminal differentiation (1, 2) and JNK2, in particular, is important in mammary tumorigenesis and tumor progression (3-8). Therefore, the involvement of JNK2 in inhibition of mammary luminal cell differentiation was investigated in normal glands and tumors. Studies found that JNK2 inhibits luminal cell populations in normal mammary ducts. Additionally, JNK2 suppresses Notch activity in stem cell niche of the developing mammary gland. In vitro assays show that control over differentiation by JNK2 is due to suppression of p53-dependent Notch1 expression. Inhibition of luminal cell populations by JNK2 is also apparent in tumor cell models regardless of p53 expression. In the p53-competent Polyoma Middle T-antigen model, Notch1 expression is suppressed by JNK2. In the absence of p53, JNK2 suppresses luminal populations independent of Notch1. In this model, decreased luminal marker expression is accompanied by increased epithelial to mesenchymal transition. It was also found that JNK2-dependent epithelial to mesenchymal transition inhibits luminal populations and is driven by JNK2-dependent suppression of Brca1. JNK2 also confers resistance to estrogen signaling inhibition, and increases the metastatic ability of tumor cells in vivo. These data establish the importance of JNK2 in mammary epithelial cell differentiation in normal glands and tumors. They also suggest that JNK2 may be an effective prognostic marker or treatment target.Cellular and Molecular Biolog

HABITAT SELECTION AND CON- AND HETEROSPECIFIC ASSOCIATIONS OF WINTERING WHOOPING CRANES AT WHEELER NATIONAL WILDLIFE REFUGE, ALABAMA

Winter ecology of the Eastern Migratory Population of whooping cranes (Grus americana) has received less detailed study than that of other life stages or the Aransas-Wood Buffalo Population. Increased winter use of novel sites by these cranes makes understanding the mechanisms contributing to habitat selection and use important for efficient conservation. As a subset of a larger and ongoing project, this study examined the individual and temporal variations of occupancy times, habitat types used, and co-occurrence with con- and heterospecifics during winters 2014-15 and 2015-16 at Wheeler National Wildlife Refuge, Alabama, while considering the effect of individual life histories (e.g., breeding status, release method). In total, 27 and 21 whooping cranes were observed during the 2 winters, respectively. Individuals varied in their habitat preference and in cooccurrence with con- and heterospecifics. Mated pairs showed a higher use of wetlands than unmated individuals, which were found more in crops left for wildlife use. Unmated individuals were more often found associating with other whooping and sandhill cranes (G. canadensis) than mated pairs. Compared to the first winter in 2014-15, the warmer temperature in 2015-16 likely influenced delayed arrival times while reduced wetland availability may be linked to shorter duration of stay and other temporal variation in habitat selection and co-occurrence. Our findings suggest that multiple management strategies would be needed for effective conservation because of varied habitat preference among individuals. Additionally, understanding environmental influence on occupancy times could offer managers management tools by being able to better predict crane arrival and duration of stay

Collaborating Across Campus to Advance Open Access Policy Compliance

In 2018, the Data and Scholarly Communication Services Unit (DSCS) at the University of Colorado Boulder began implementing two open access (OA) policy workflows with the aim of increasing content in the institutional repository CU Scholar, expanding awareness of the campus OA policy that was passed in 2015, and decreasing the burden on researchers for participation in the policy. DSCS leveraged collaborative relationships with other library departments and campus units in order to mobilize the data, infrastructure, procedures, and documentation to execute these workflows. The Directory of Open Access Journals (DOAJ) workflow identifies existing open access publications by CU Boulder faculty and mediates deposit in order to make them available in CU Scholar. The liaison outreach workflow partners with liaison librarians to request from faculty preprints and author’s final manuscripts of publications in which the publisher version may have copyright restrictions. At present, the DOAJ workflow has resulted in 754 articles deposited in CU Scholar, and the liaison outreach workflow has resulted in 91 articles deposited. Each of these workflows pose challenges that have required flexibility, experimentation, and clear communication between stakeholders. This case study, which includes detailed descriptions of both open access policy workflows, initial results, and plans for future implementation, may serve as a guide for other institutions wishing to adopt and/or adapt institutional repository workflows and forge collaborative relationships to further open access initiatives in their local context

Dynamic Voltage Rail Audio Amplifier

The goal of this project is to create a high-quality, power-efficient audio amplifier. Most modern audio amplifiers use a constant amount of power regardless of the signal that is being amplified. This means that both loud and quiet portions of the audio signal require the same amount of power to amplify. The idea for this high-quality, power-efficient audio amplifier is that the quieter portions of the audio signal can be amplified using less power. This will be achieved by first analyzing the audio signal and controlling the power source based on the signal’s needs. Therefore, louder parts of the audio signal will use the typical amount of power, while quieter parts of the signal will not use as much power. When comparing a standard audio amplifier and the high-quality power-efficient audio amplifier, the average power usage for the power-efficient amplifier should be less than the standard amplifier

Engaged Citizenship through Campus-Level Democratic Processes: A Librarian and Graduate Student Collaboration on Open Access Policy Adoption

INTRODUCTION While faculty votes to establish open access (OA) policies leverage one particular campus- level democratic mechanism in the name of advancing scholarly communication, other processes, including student government actions, can also play significant roles in OA policy adoption and related efforts. As early career researchers, graduate students are particularly well-poised to engage with campus-level democratic institutions in order to bring about change in scholarly communication. DESCRIPTION OF PROGRAM This case study details a multi-year collaboration between librarians and graduate students at the University of Colorado Boulder aimed at the development and adoption of a campus OA policy. Librarians and graduate students worked together to plan for and sustain momentum throughout the process of building formal support for the policy through student government and faculty assembly resolutions, drafting policy language, and shepherding the proposed policy through numerous meetings and committees all the way up to and including its formal adoption. This collaboration through engaged citizenship at the campus level also led to a number of unintended benefits to both librarians and graduate students involved. NEXT STEPS AND CONCLUSIONS Ultimately, the CU Boulder collaboration between librarians and graduate students led to significant scholarly communication achievements largely through the utilization of campus-level democratic processes. The case study concludes with a look at next steps for implementing the OA policy across campus as well as a discussion of the labor involved in such efforts, including implications for graduate student involvement in scholarly communication initiatives

Is contact nucleation caused by pressure perturbation?

The reason why ice nucleation is more efficient by contact nucleation than by immersion nucleation has been elusive for over half a century. Six proposed mechanisms are summarized in this study. Among them, the pressure perturbation hypothesis, which arose from recent experiments, can qualitatively explain nearly all existing results relevant to contact nucleation. To explore the plausibility of this hypothesis in a more quantitative fashion and to guide future investigations, this study assessed the magnitude of pressure perturbation needed to cause contact nucleation and the associated spatial scales. The pressure perturbations needed were estimated using measured contact nucleation efficiencies for illite and kaolinite, obtained from previous experiments, and immersion freezing temperatures, obtained from well-established parameterizations. Pressure perturbations were obtained by assuming a constant pressure perturbation or a Gaussian distribution of the pressure perturbation. The magnitudes of the pressure perturbations needed were found to be physically reasonable, being achievable through possible mechanisms, including bubble formation and breakup, Laplace pressure arising from the distorted contact line, and shear. The pressure perturbation hypothesis provides a physically based and experimentally constrainable foundation for parameterizing contact nucleation that may be useful in future cloud-resolving models

The Mass Distribution of Stellar-Mass Black Holes

We perform a Bayesian analysis of the mass distribution of stellar-mass black holes using the observed masses of 15 low-mass X-ray binary systems undergoing Roche lobe overflow and five high-mass, wind-fed X-ray binary systems. Using Markov Chain Monte Carlo calculations, we model the mass distribution both parametrically---as a power law, exponential, gaussian, combination of two gaussians, or log-normal distribution---and non-parametrically---as histograms with varying numbers of bins. We provide confidence bounds on the shape of the mass distribution in the context of each model and compare the models with each other by calculating their relative Bayesian evidence as supported by the measurements, taking into account the number of degrees of freedom of each model. The mass distribution of the low-mass systems is best fit by a power-law, while the distribution of the combined sample is best fit by the exponential model. We examine the existence of a "gap" between the most massive neutron stars and the least massive black holes by considering the value, M_1%, of the 1% quantile from each black hole mass distribution as the lower bound of black hole masses. The best model (the power law) fitted to the low-mass systems has a distribution of lower-bounds with M_1% > 4.3 Msun with 90% confidence, while the best model (the exponential) fitted to all 20 systems has M_1% > 4.5 Msun with 90% confidence. We conclude that our sample of black hole masses provides strong evidence of a gap between the maximum neutron star mass and the lower bound on black hole masses. Our results on the low-mass sample are in qualitative agreement with those of Ozel, et al (2010).Comment: 56 pages, 22 figures, 9 tables, as accepted by Ap