A pharmacological cocktail for arresting actin dynamics in living cells.

The actin cytoskeleton is regulated by factors that influence polymer assembly, disassembly, and network rearrangement. Drugs that inhibit these events have been used to test the role of actin dynamics in a wide range of cellular processes. Previous methods of arresting actin rearrangements take minutes to act and work well in some contexts, but can lead to significant actin reorganization in cells with rapid actin dynamics, such as neutrophils. In this paper, we report a pharmacological cocktail that not only arrests actin dynamics but also preserves the structure of the existing actin network in neutrophil-like HL-60 cells, human fibrosarcoma HT1080 cells, and mouse NIH 3T3 fibroblast cells. Our cocktail induces an arrest of actin dynamics that initiates within seconds and persists for longer than 10 min, during which time cells maintain their responsivity to external stimuli. With this cocktail, we demonstrate that actin dynamics, and not simply morphological polarity or actin accumulation at the leading edge, are required for the spatial persistence of Rac activation in HL-60 cells. Our drug combination preserves the structure of the existing cytoskeleton while blocking actin assembly, disassembly, and rearrangement, and should prove useful for investigating the role of actin dynamics in a wide range of cellular signaling contexts

Changing Frames of Ethanol Policy in Congress and the Media

"This paper will focus on a particular slice of this story: namely, the evolving “frames” used to discuss ethanol policy. Frames are the issue areas deemed relevant to the evaluation of a particular policy. New frames, including global food prices, international trade regimes, and the budget deficit, were added across time to older ethanol frames, including the environment, agriculture, and energy security, to create an increasingly complex issue environment for ethanol policymaking. Specifically, this thesis will investigate the origination and transmission of these new frames. Often treated as a “black box” phenomenon by political scientists, the creation and adoption of new policy frames has important implications for understanding preference-formation and congressional policymaking. In the pages that follow, I will attempt to address this critical question. Where did Congress “find” new ethanol frames? Did members of Congress frame ethanol policy for the media, or vice versa? And why did some groups adopt new frames while others lagged behind?"-- from page 5

EHR-Based Care Coordination Performance Measures in Ambulatory Care

Describes electronic health record-based measures for assessing coordination in referrals, including information communicated with referral, communication to patient, and specialist report to primary care physician. Offers preliminary evaluation findings

Uncovering middle managers' role in healthcare innovation implementation

<p>Abstract</p> <p>Background</p> <p>Middle managers have received little attention in extant health services research, yet they may have a key role in healthcare innovation implementation. The gap between evidence of effective care and practice may be attributed in part to poor healthcare innovation implementation. Investigating middle managers' role in healthcare innovation implementation may reveal an opportunity for improvement. In this paper, we present a theory of middle managers' role in healthcare innovation implementation to fill the gap in the literature and to stimulate research that empirically examines middle managers' influence on innovation implementation in healthcare organizations.</p> <p>Discussion</p> <p>Extant healthcare innovation implementation research has primarily focused on the roles of physicians and top managers. Largely overlooked is the role of middle managers. We suggest that middle managers influence healthcare innovation implementation by diffusing information, synthesizing information, mediating between strategy and day-to-day activities, and selling innovation implementation.</p> <p>Summary</p> <p>Teamwork designs have become popular in healthcare organizations. Because middle managers oversee these team initiatives, their potential to influence innovation implementation has grown. Future research should investigate middle managers' role in healthcare innovation implementation. Findings may aid top managers in leveraging middle managers' influence to improve the effectiveness of healthcare innovation implementation.</p

Transform-limited pulses are not optimal for resonant multiphoton transitions

Maximizing nonlinear light-matter interactions is a primary motive for compressing laser pulses to achieve ultrashort transform limited pulses. Here we show how, by appropriately shaping the pulses, resonant multiphoton transitions can be enhanced significantly beyond the level achieved by maximizing the pulse's peak intensity. We demonstrate the counterintuitive nature of this effect with an experiment in a resonant two-photon absorption, in which, by selectively removing certain spectral bands, the peak intensity of the pulse is reduced by a factor of 40, yet the absorption rate is doubled. Furthermore, by suitably designing the spectral phase of the pulse, we increase the absorption rate by a factor of 7.Comment: 4 pages, 3 figure

Consent Is Not Enough: Why States Must Respect the Intensity Threshold in Transnational Conflict

It is widely accepted that a state cannot treat a struggle with an organized non-state actor as an armed conflict until the violence crosses a minimum threshold of intensity. For instance, during the recent standoff at the Oregon wildlife refuge, the US. government could have lawfully used force pursuant to its domestic law enforcement and human rights obligations, but President Obama could not have ordered a drone strike on the protesters. The reason for this uncontroversial rule is simple-not every riot or civil disturbance should be treated like a war. But what if President Obama had invited Canada to bomb the protestors-once the United States consented, would all bets be off? Can an intervening state use force that would be illegal for the host state to use itself? The silence on this issue is dangerous, in no small part because these once-rare conflicts are now commonplace. States are increasingly using force against organized non-state actors outside of the states\u27 own territories-usually, though not always, with the consent of the host state. What constrains the scope of the host state\u27s consent? And can the intervening state always presume that consent is valid? This Article argues that a host state\u27s authority to consent is limited and that intervening states cannot treat consent as a blank check. Accordingly, even in consent-based interventions, the logic andf oundational norms of the internationall egal order require both consent-giving and consent-receiving states to independently evaluate what legal regime governs-this will often turn on whether the intensity threshold has been met. Ifa non-international armed conflict exists, the actions of the intervening state are governed by international humanitarian law; if not, its actions are governed instead by its own and the host state\u27s human rights obligations

Consent Is Not Enough: Why States Must Respect the Intensity Threshold in Transnational Conflict

It is widely accepted that a state cannot treat a struggle with an organized non-state actor as an armed conflict until the violence crosses a minimum threshold of intensity. For instance, during the recent standoff at the Oregon wildlife refuge, the US. government could have lawfully used force pursuant to its domestic law enforcement and human rights obligations, but President Obama could not have ordered a drone strike on the protesters. The reason for this uncontroversial rule is simple-not every riot or civil disturbance should be treated like a war. But what if President Obama had invited Canada to bomb the protestors-once the United States consented, would all bets be off? Can an intervening state use force that would be illegal for the host state to use itself? The silence on this issue is dangerous, in no small part because these once-rare conflicts are now commonplace. States are increasingly using force against organized non-state actors outside of the states\u27 own territories-usually, though not always, with the consent of the host state. What constrains the scope of the host state\u27s consent? And can the intervening state always presume that consent is valid? This Article argues that a host state\u27s authority to consent is limited and that intervening states cannot treat consent as a blank check. Accordingly, even in consent-based interventions, the logic andf oundational norms of the internationall egal order require both consent-giving and consent-receiving states to independently evaluate what legal regime governs-this will often turn on whether the intensity threshold has been met. Ifa non-international armed conflict exists, the actions of the intervening state are governed by international humanitarian law; if not, its actions are governed instead by its own and the host state\u27s human rights obligations

Platelets Recognize Brain-Specific Glycolipid Structures, Respond to Neurovascular Damage and Promote Neuroinflammation

Platelets respond to vascular damage and contribute to inflammation, but their role in the neurodegenerative diseases is unknown. We found that the systemic administration of brain lipid rafts induced a massive platelet activation and degranulation resulting in a life-threatening anaphylactic-like response in mice. Platelets were engaged by the sialated glycosphingolipids (gangliosides) integrated in the rigid structures of astroglial and neuronal lipid rafts. The brain-abundant gangliosides GT1b and GQ1b were specifically recognized by the platelets and this recognition involved multiple receptors with P-selectin (CD62P) playing the central role. During the neuroinflammation, platelets accumulated in the central nervous system parenchyma, acquired an activated phenotype and secreted proinflammatory factors, thereby triggering immune response cascades. This study determines a new role of platelets which directly recognize a neuronal damage and communicate with the cells of the immune system in the pathogenesis of neurodegenerative diseases

Radiocarbon Date List X: Baffin Bay, Baffin Island, Iceland, Labrador Sea, and the Northern North Atlantic

Date List X contains an annotated listing of 213 radiocarbon dates determined on samples from marine and terrestrial environments. The marine samples were collected from the East Greenland, Iceland, Spitzbergen, and Norwegian margins, Baffin Bay, and Labrador Sea. The terrestrial samples were collected from Vestfirdir, Iceland and Baffin Island. The samples were submitted by INSTAAR and researchers affiliated with INSTAAR\u27s Micropaleontology Laboratory under the direction of Dr.’s John T. Andrews and Anne E. Jennings. All of the dates from marine sediment cores were determined from either shells or foraminifera (both benthic and planktic). All dates were obtained by the Accelerator Mass Spectrometry (AMS) method. Regions of concentrated marine research include: Baffin Bay, Baffin Island, Labrador Sea, East Greenland fjords, shelf and slope, Denmark Strait, the southwestern and northwestern Iceland shelves, and Vestfirdir, Iceland. The non-marine radiocarbon dates are from peat, wood, plant microfossils, and mollusc. The radiocarbon dates have been used to address a variety of research objectives such as: 1. determining the timing of northern hemisphere high latitude environmental changes including glacier advance and retreat, and 2. assessing the accuracy of a fluctuating reservoir correction. Thus, most of the dates constrain the timing, rate, and interaction of late Quaternary paleoenvironmental fluctuations in sea level, glacier extent, sediment input, and changes in ocean circulation patterns. Where significant, stratigraphic and sample contexts are presented for each core to document the basis for interpretations