Overwintering Locations, Migrations, and Fidelity of Radio-Tagged Dolly Varden in the Hulahula River, Arctic National Wildlife Refuge, 2007–09

Essential overwintering habitats for anadromous Dolly Varden Salvelinus malma on Alaska’s North Slope appear to be limited to a small number of perennial springs, primarily in eastern Brooks Range drainages. Because future petrochemical development in the region continues to be a possibility, and development would require large quantities of freshwater, we sought to identify and document the overwintering areas used by Dolly Varden in the Hulahula River, eastern Brooks Range. In August 2007, we implanted 52 Dolly Varden with multi-year radio transmitters at a known overwintering area in the lower Hulahula River. Other wintering areas were located during 11 aerial surveys conducted over the next 2.5 years. A stationary receiver located in the lower Hulahula River provided migration timing information. Radio-tagged Dolly Varden used four discrete areas with perennial springs for overwintering in the Hulahula River drainage. The springs, totaling approximately 12 km in stream length, were located between river km 40 and 105. Radio-tagged Dolly Varden migrated downstream on their way to the Beaufort Sea in early June. Most tagged fish known to have survived the summer at sea returned to the Hulahula River during late July and August, but seven fish overwintered in other North Slope drainages. Within the Hulahula River drainage, 15 fish overwintered in more than one area during the three winters of the project, but only the four identified perennial spring areas were used. These data clearly indicate that the perennial springs in the Hulahula River are essential overwintering habitats for Dolly Varden.Les aires de concentration hivernales essentielles du Dolly Varden Salvelinus malma anadrome sur la North Slope de l’Alaska semblent limitées à un petit nombre de sources pérennes, principalement dans les bassins hydrographiques de l’est de la chaîne de Brooks. Puisqu’il est toujours possible qu’il y ait des aménagements pétrochimiques dans la région et que ceux-ci demanderaient de grandes quantités d’eau douce, nous avons tâché de déterminer les aires de concentration hivernales du Dolly Varden dans la rivière Hulahula faisant partie de l’est de la chaîne de Brooks, et nous les avons répertoriées. En août 2007, nous avons installé des émetteurs radio pluriannuels sur 52 poissons Dolly Varden dans une aire de concentration hivernale connue faisant partie de la rivière Hulahula inférieure. D’autres aires de concentration hivernales ont été repérées grâce à 11 levés aériens effectués au cours des 2,5 années qui ont suivi. Un récepteur fixe situé dans la rivière Hulahula inférieure nous a permis de relever des données sur le moment de la migration. Les Dolly Varden dotés d’émetteurs radio ont utilisé quatre sources discrètes où se trouvent des sources pérennes pour passer l’hiver, dans le bassin versant de la rivière Hulahula. Les sources, qui s’étendent sur une douzaine de kilomètres de longueur, étaient situées entre les kilomètres 40 et 105 de la rivière. Les Dolly Varden munis d’émetteurs radio ont migré en aval, en route vers la mer de Beaufort au début juin. La plupart des poissons avec émetteur ont survécu l’été à la mer et ont regagné la rivière Hulahula vers la fin de juillet et en août, mais sept poissons ont passé l’hiver dans d’autres bassins versants de la North Slope. Dans le bassin versant de la rivière Hulahula, 15 poissons ont passé l’hiver dans plus d’une aire au cours des trois hivers visés par le projet, mais seules les quatre sources pérennes déterminées ont été utilisées. Ces données indiquent clairement que les sources pérennes de la rivière Hulahula sont des aires de concentration hivernales essentielles pour le Dolly Varden

New strategies for HIV surveillance in resource-constrained settings: an overview.

Additional funding recently became available to help resource-constrained countries scale up their HIV treatment and prevention activities. This increased funding is accompanied by an increased demand for accountability from stakeholders. Many countries will need to make substantial improvements in their current HIV surveillance methods to monitor the collective national impact of these treatment and prevention initiatives. However, whereas most resource-constrained countries have monitored the prevalence of HIV, they have collected little information on other events in the HIV disease process, such as HIV incidence, rate of HIV drug resistance, number of deaths due to AIDS and only modest emphasis has been placed on AIDS reporting in generalized epidemics, resulting in severe underreporting. In addition, data on mortality trends are often not gathered. Furthermore, less than half of the countries with low-level/concentrated epidemics have tailored their surveillance systems to the local epidemic, behavioral surveillance is often not present, an integrated analysis of data is not widespread, and data are rarely used to inform policy. In January 2004, a conference was convened in Addis Ababa, Ethiopia, to examine new strategies for surveillance in resource-constrained countries, and their use in monitoring and evaluating HIV activities. This supplement summarizes the newest approaches and lessons learned for HIV/AIDS surveillance, based on presentations and discussions from that conference. This article provides an overview of HIV/AIDS surveillance in resource-constrained settings and discusses the history, current approaches, and future directions for HIV/AIDS surveillance in generalized and low-level/concentrated epidemics

Contemplating Mindfulness at Work: An Integrative Review

Mindfulness research activity is surging within organizational science. Emerging evidence across multiple fields suggests that mindfulness is fundamentally connected to many aspects of workplace functioning, but this knowledge base has not been systematically integrated to date. This review coalesces the burgeoning body of mindfulness scholarship into a framework to guide mainstream management research investigating a broad range of constructs. The framework identifies how mindfulness influences attention, with downstream effects on functional domains of cognition, emotion, behavior, and physiology. Ultimately, these domains impact key workplace outcomes, including performance, relationships, and well-being. Consideration of the evidence on mindfulness at work stimulates important questions and challenges key assumptions within management science, generating an agenda for future research

A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018

Sex differences and effects of prenatal exposure to excess testosterone on ventral tegmental area dopamine neurons in adult sheep

Prenatal testosterone (T) excess in sheep results in a wide array of reproductive neuroendocrine deficits and alterations in motivated behavior. The ventral tegmental area (VTA) plays a critical role in reward and motivated behaviors and is hypothesised to be targeted by prenatal T. Here we report a sex difference in the number VTA dopamine cells in the adult sheep, with higher numbers of tyrosine hydroxylase (TH)‐immunoreactive (‐ir) cells in males than females. Moreover, prenatal exposure to excess T during either gestational days 30–90 or 60–90 resulted in increased numbers of VTA TH‐ir cells in adult ewes compared to control females. Stereological analysis confirmed significantly greater numbers of neurons in the VTA of males and prenatal T‐treated ewes, which was primarily accounted for by greater numbers of TH‐ir cells. In addition, immunoreactivity for TH in the cells was denser in males and prenatal T‐treated females, suggesting that sex differences and prenatal exposure to excess T affects both numbers of cells expressing TH and the protein levels within dopamine cells. Sex differences were also noted in numbers of TH‐ir cells in the substantia nigra, with more cells in males than females. However, prenatal exposure to excess T did not affect numbers of TH‐ir cells in the substantia nigra, suggesting that this sex difference is organised independently of prenatal actions of T. Together, these results demonstrate sex differences in the sheep VTA dopamine system which are mimicked by prenatal treatment with excess T.We report a sex difference in ventral tegmental area (VTA) dopamine cells in the adult sheep with higher numbers of tyrosine hydroxylase (TH)‐immunoreactive cells in males than females. Moreover, prenatal exposure to excess T during gestational days 30–90 or 60–90 caused increased numbers of VTA TH‐immunoreactive cells in adult ewes compared to control females. Sex differences were also demonstrated in the substantia nigra, but prenatal T had no effect on TH in this area. Results indicate that sex differences and prenatal exposure to excess T affects both numbers of cells expressing TH and the protein levels in the VTA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111123/1/ejn12871.pd

A Framework for Treating Uncertainty to Facilitate Waste Disposal Decision Making - Application of the Approach to GCD Performance Assessment

This paper presents an approach for treating uncertainty in the performance assessment process to efficiently address regulatory performance objectives for radioactive waste disposal and discusses the application of the approach at the Greater Confinement Disposal site. In this approach, the performance assessment methodology uses probabilistic risk assessment concepts to guide effective decisions about site characterization activities and provides a path toward reasonable assurance regarding regulatory compliance decisions. Although the approach is particularly amenable to requirements that are probabilistic in nature, the approach is also applicable to deterministic standards such as the dose-based and concentration-based requirements

A Single Tri-Epitopic Antibody Virtually Recapitulates the Potency of a Combination of Three Monoclonal Antibodies in Neutralization of Botulinum Neurotoxin Serotype A.

The standard of treatment for botulism, equine antitoxin, is a foreign protein with associated safety issues and a short serum half-life which excludes its use as a prophylactic antitoxin and makes it a less-than-optimal therapeutic. Due to these limitations, a recombinant monoclonal antibody (mAb) product is preferable. It has been shown that combining three mAbs that bind non-overlapping epitopes leads to highly potent botulinum neurotoxin (BoNT) neutralization. Recently, a triple human antibody combination for BoNT/A has demonstrated potent toxin neutralization in mouse models with no serious adverse events when tested in a Phase I clinical trial. However, a triple antibody therapeutic poses unique development and manufacturing challenges. Thus, potentially to streamline development of BoNT antitoxins, we sought to achieve the potency of multiple mAb combinations in a single IgG-based molecule that has a long serum half-life. The design, production, and testing of a single tri-epitopic IgG1-based mAb (TeAb) containing the binding sites of each of the three parental BoNT/A mAbs yielded an antibody of nearly equal potency to the combination. The approach taken here could be applied to the design and creation of other multivalent antibodies that could be used for a variety of applications, including toxin elimination

The political import of deconstruction—Derrida’s limits?: a forum on Jacques Derrida’s specters of Marx after 25 Years, part I

Jacques Derrida delivered the basis of The Specters of Marx: The State of the Debt, the Work of Mourning, & the New International as a plenary address at the conference ‘Whither Marxism?’ hosted by the University of California, Riverside, in 1993. The longer book version was published in French the same year and appeared in English and Portuguese the following year. In the decade after the publication of Specters, Derrida’s analyses provoked a large critical literature and invited both consternation and celebration by figures such as Antonio Negri, Wendy Brown and Frederic Jameson. This forum seeks to stimulate new reflections on Derrida, deconstruction and Specters of Marx by considering how the futures past announced by the book have fared after an eventful quarter century. Maja Zehfuss, Antonio Vázquez-Arroyo and Dan Bulley and Bal Sokhi-Bulley offer sharp, occasionally exasperated, meditations on the political import of deconstruction and the limits of Derrida’s diagnoses in Specters of Marx but also identify possible paths forward for a global politics taking inspiration in Derrida’s work of the 1990s

Althaia

https://red.mnstate.edu/althaia/1001/thumbnail.jp

Smoking decreases the response of human lung macrophages to double-stranded RNA by reducing TLR3 expression

Abstract Background Cigarette smoking is associated with increased frequency and duration of viral respiratory infections, but the underlying mechanisms are incompletely defined. We investigated whether smoking reduces expression by human lung macrophages (Mø) of receptors for viral nucleic acids and, if so, the effect on CXCL10 production. Methods We collected alveolar macrophages (AMø) by bronchoalveolar lavage of radiographically-normal lungs of subjects undergoing bronchoscopies for solitary nodules (n = 16) and of volunteers who were current or former smokers (n = 7) or never-smokers (n = 13). We measured expression of mRNA transcripts for viral nucleic acid receptors by real-time PCR in those AMø and in the human Mø cell line THP-1 following phorbol myristate acetate/vitamin D3 differentiation and exposure to cigarette smoke extract, and determined TLR3 protein expression using flow cytometry and immunohistochemistry. We also used flow cytometry to examine TLR3 expression in total lung Mø from subjects undergoing clinically-indicated lung resections (n = 25). Of these, seven had normal FEV1 and FEV1/FVC ratio (three former smokers, four current smokers); the remaining 18 subjects (14 former smokers; four current smokers) had COPD of GOLD stages I-IV. We measured AMø production of CXCL10 in response to stimulation with the dsRNA analogue poly(I:C) using Luminex assay. Results Relative to AMø of never-smokers, AMø of smokers demonstrated reduced protein expression of TLR3 and decreased mRNA for TLR3 but not TLR7, TLR8, TLR9, RIG-I, MDA-5 or PKR. Identical changes in TLR3 gene expression were induced in differentiated THP-1 cells exposed to cigarette smoke-extract in vitro for 4 hours. Among total lung Mø, the percentage of TLR3-positive cells correlated inversely with active smoking but not with COPD diagnosis, FEV1% predicted, sex, age or pack-years. Compared to AMø of never-smokers, poly(I:C)-stimulated production of CXCL10 was significantly reduced in AMø of smokers. Conclusions Active smoking, independent of COPD stage or smoking duration, reduces both the percent of human lung Mø expressing TLR3, and dsRNA-induced CXCL10 production, without altering other endosomal or cytoplasmic receptors for microbial nucleic acids. This effect provides one possible mechanism for increased frequency and duration of viral lower respiratory tract infections in smokers. Trial registration ClinicalTrials.gov NCT00281190 , NCT00281203 and NCT00281229 .http://deepblue.lib.umich.edu/bitstream/2027.42/134585/1/12931_2012_Article_1336.pd