Planning for Failure? Addressing Outside Stakeholders in Collaborative Basin Planning

In recent decades, watershed managers have increasingly turned to collaborative models of governance for water resource planning in the Western United States. By involving a wide array of stakeholders in decision-making, these place-based partnerships promise many benefits: better understanding of local needs, increased public support, and reduced conflict. Yet, many basins involve powerful, non-local stakeholders, who may not participate in place-based partnerships but can still hinder the collaborative process and derail implementation. One such case is the Icicle Creek Subbasin of Washington State, where a local partnership has been involved in comprehensive watershed planning since 2012. In order to mitigate the impact of droughts and boost instream flow, the Icicle Work Group’s plans have included infrastructural upgrades to storage dams in a federal wilderness area. These projects have drawn intense criticism and threats of litigation from conservation and recreational organizations, who see their wilderness interests threatened by the projects. This research examines the Icicle Creek case study and asks the following research question: How did the Icicle Work Group incorporate input from external stakeholders into their collaborative planning process? Did their process address external concerns in ways that mitigate the chance of future conflict? This study uses the well-documented environmental review process to identify the key concerns of external stakeholders and examine how effectively the collaborative partnership was able to address those concerns. Comment letters from external stakeholder organizations were analyzed using reflexive thematic analysis and the agency responses were identified for each theme. Ultimately, the analysis found that the key concerns of outside stakeholders remained throughout the process, as the agencies and work group were unwilling to make major modifications to their plan. This suggests a number of conclusions: 1) place-based partnerships favor maintaining internal consensus over avoiding conflicts with outside groups; 2) the environmental review process is a limited platform for outside stakeholders to shape planning efforts; 3) state agencies involved in the collaborative planning should consider should delegating the environmental review process to an outside agency to avoid perceptions of a conflict of interest; and 4) watersheds with federal wilderness may not be well-suited for local collaboration

First experimental evidence of one-dimensional plasma modes in superconducting thin wires

We have studied niobium superconducting thin wires deposited onto a SrTiO$_{3}$ substrate. By measuring the reflection coefficient of the wires, resonances are observed in the superconducting state in the 130 MHz to 4 GHz range. They are interpreted as standing wave resonances of one-dimensional plasma modes propagating along the superconducting wire. The experimental dispersion law, $\omega$ versus $q$, presents a linear dependence over the entire wave vector range. The modes are softened as the temperature increases close the superconducting transition temperature. Very good agreement are observed between our data and the dispersion relation predicted by Kulik and Mooij and Sch\"on.Comment: Submitted to Physical review Letter

NOXA-Induced Alterations in the Bax/Smac Axis Enhance Sensitivity of Ovarian Cancer Cells to Cisplatin

Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy

Mechanism of action for N-substituted benzamide-induced apoptosis

We have analysed the mechanism of action for induction of apoptosis by N-substituted benzamides using declopramide as a lead compound. We show here that declopramide at doses above 250 μM in the mouse 70Z/3 pre-B cell line or in the human promyeolocytic cancer cell line HL60 induced cytochrome c release into the cytosol and caspase-9 activation. The broad spectrum caspase inhibitor zVADfmk and caspase-9 inhibitor zLEDHfmk inhibited apoptosis and improved cell viability when administrated to cells 1 h before exposure to declopramide, whereas the caspase-8 inhibitor zIEDHfmk had less effect. Also, the over expression of Bcl-2 by transfection in 70Z/3 cells inhibited declopramide-induced apoptosis. Prior to the induction of apoptosis, a G2/M cell cycle block was induced by declopramide. The cell cycle block was also observed in the presence of broad spectrum caspase inhibitor zVADfmk and in a transfectant expressing high levels of Bcl-2. Furthermore, while p53 was induced in 70Z/3 cells by declopramide, neither the apoptotic mechanism nor the G2/M cell cycle block were dependent on p53 activation since both effects were also seen in p53 deficient HL60 cells after addition of declopramide

Coupled Folding and Specific Binding: Fishing for Amphiphilicity

Proteins are uniquely capable of identifying targets with unparalleled selectivity, but, in addition to the precision of the binding phenomenon, nature has the ability to find its targets exceptionally quickly. Transcription factors for instance can bind to a specific sequence of nucleic acids from a soup of similar, but not identical DNA strands, on a timescale of seconds. This is only possible with the enhanced kinetics provided for by a natively disordered structure, where protein folding and binding are cooperative processes. The secondary structures of many proteins are disordered under physiological conditions. Subsequently, the disordered structures fold into ordered structures only when they bind to their specific targets. Induced folding of the protein has two key biological advantages. First, flexible unstructured domains can result in an intrinsic plasticity that allows them to accommodate targets of various size and shape. And, second, the dynamics of this folding process can result in enhanced binding kinetics. Several groups have hypothesized the acceleration of binding kinetics is due to induced folding where a “fly-casting” effect has been shown to break the diffusion-limited rate of binding. This review describes experimental results in rationally designed peptide systems where the folding is coupled to amphiphilicity and biomolecular activity

Lethality and Developmental Delay in Drosophila melanogaster Larvae after Ingestion of Selected Pseudomonas fluorescens Strains

The fruit fly, Drosophila melanogaster, is a well-established model organism for probing the molecular and cellular basis of physiological and immune system responses of adults or late stage larvae to bacterial challenge. However, very little is known about the consequences of bacterial infections that occur in earlier stages of development. We have infected mid-second instar larvae with strains of Pseudomonas fluorescens to determine how infection alters the ability of larvae to survive and complete development.We mimicked natural routes of infection using a non-invasive feeding procedure to study the toxicity of the three sequenced P. fluorescens strains (Pf0-1, SBW25, and Pf-5) to Drosophila melanogaster. Larvae fed with the three strains of P. fluorescens showed distinct differences in developmental trajectory and survival. Treatment with SBW25 caused a subset of insects to die concomitant with a systemic melanization reaction at larval, pupal or adult stages. Larvae fed with Pf-5 died in a dose-dependent manner with adult survivors showing eye and wing morphological defects. In addition, larvae in the Pf-5 treatment groups showed a dose-dependent delay in the onset of metamorphosis relative to control-, Pf0-1-, and SBW25-treated larvae. A functional gacA gene is required for the toxic properties of wild-type Pf-5 bacteria.These experiments are the first to demonstrate that ingestion of P. fluorescens bacteria by D. melanogaster larvae causes both lethal and non-lethal phenotypes, including delay in the onset of metamorphosis and morphological defects in surviving adult flies, which can be decoupled

CD40L induces multidrug resistance to apoptosis in breast carcinoma and lymphoma cells through caspase independent and dependent pathways

BACKGROUND: CD40L was found to reduce doxorubicin-induced apoptosis in non Hodgkin's lymphoma cell lines through caspase-3 dependent mechanism. Whether this represents a general mechanism for other tumor types is unknown. METHODS: The resistance induced by CD40L against apoptosis induced by a panel of cytotoxic chemotherapeutic drugs in non Hodgkin's lymphoma and breast carcinoma cell lines was investigated. RESULTS: Doxorubicin, cisplatyl, etoposide, vinblastin and paclitaxel increased apoptosis in a dose-dependent manner in breast carcinoma as well as in non Hodgkin's lymphoma cell lines. Co-culture with irradiated L cells expressing CD40L significantly reduced the percentage of apoptotic cells in breast carcinoma and non Hodgkin's lymphoma cell lines treated with these drugs. In breast carcinoma cell lines, these 5 drugs induced an inconsistent increase of caspase-3/7 activity, while in non Hodgkin's lymphoma cell lines all 5 drugs increased caspase-3/7 activity up to 28-fold above baseline. Co-culture with CD40L L cells reduced (-39% to -89%) the activation of caspase-3/7 induced by these agents in all 5 non Hodgkin's lymphoma cell lines, but in none of the 2 breast carcinoma cell lines. Co culture with CD40L L cells also blocked the apoptosis induced by exogenous ceramides in breast carcinoma and non Hodgkin's lymphoma cell lines through a caspase-3-like, 8-like and 9-like dependent pathways. CONCLUSION: These results indicate that CD40L expressed on adjacent non tumoral cells induces multidrug resistance to cytotoxic agents and ceramides in both breast carcinoma and non Hodgkin's lymphoma cell lines, albeit through a caspase independent and dependent pathway respectively

Governing Oregon: Continuity and Change

At the end of the twentieth century, the state government of Oregon was routinely entangled in intense partisan conflict, with opposing sides waging bitter battles in elections, the legislature, and the courts. Many of the most important state laws—such as Measure 5, which capped property taxes—were decided through the initiative process rather than by lawmakers in Salem. As the twenty-first century began, this political dynamic began to shift. Partisan conflict in the capitol grew less rancorous, legislative gridlock eased, and ballot initiatives lost their central role in defining Oregon politics. Less visible changes reshaped issues from agricultural policy to tribal government. This shifting dynamic coincided with significant transformations in Oregon’s economy and cultural life. The state’s economy sustained severe blows twice in the early 2000s, but by 2014, Oregon boasted one of the fastest-growing economies in the nation. Along with economic expansion, Oregon’s population grew in both size and diversity. Despite these powerful forces of change, other aspects of Oregon political life remained entrenched, including the deep urban-rural divide and the state’s problematic fiscal system. With contributions from twenty-seven leading experts and political insiders, Governing Oregon: Continuity and Change offers insight into the people, political practices, governing institutions, and public policies of Oregon. It will be of tremendous value to political scientists, public servants, and engaged citizens alike