19,526 research outputs found

    Resilience of a tropical sport fish population to a severe cold event varies across five estuaries in southern Florida

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    For species that are closely managed, understanding population resilience to environmental and anthropogenic disturbances (i.e., recovery trajectories across broad spatial areas) can guide which suite of management actions are available to mitigate any impacts. During January 2010, an extreme cold event in south Florida caused widespread mortality of common snook, Centropomus undecimalis, a popular sport fish. Interpretation of trends using fishery-independent monitoring data in five south Florida estuaries showed that changes in catch rates of adult snook (\u3e500 mm standard length) varied between no effects postevent to large effects and 4-yr recoveries. The reasons for the variation across estuaries are unknown, but are likely related to differences in estuary geomorphology and habitat availability (e.g., extent of deep rivers and canals) and differences in the proportions of behavior contingents (i.e., segments of the population that use divergent movement tactics) that place snook in different areas of the estuary during winter. Emerging awareness of the presence of behavior contingents, identification of overwintering sites, and improvements of abundance indices in remote nursery habitats should provide a better understanding of population resilience to disturbance events for snook. Given that changes in the frequency of short-lived, severe cold events are currently unknown, the findings and management actions described here for a tropical species living at the edge of its distribution should be useful to scientists forecasting the effects of climate change

    Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients.

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    Background: The colorectal cancer antigen GUCY2C exhibits unique split tolerance, evoking antigen-specific CD8+, but not CD4+, T-cell responses that deliver anti-tumor immunity without autoimmunity in mice. Here, the cancer vaccine Ad5-GUCY2C-PADRE was evaluated in a first-in-man phase I clinical study of patients with early-stage colorectal cancer to assess its safety and immunological efficacy. Methods: Ten patients with surgically-resected stage I or stage II (pN0) colon cancer received a single intramuscular injection of 1011 viral particles (vp) of Ad5-GUCY2C-PADRE. Safety assessment and immunomonitoring were carried out for 6 months following immunization. This trial employed continual monitoring of both efficacy and toxicity of subjects as joint primary outcomes. Results: All patients receiving Ad5-GUCY2C-PADRE completed the study and none developed adverse events greater than grade 1. Antibody responses to GUCY2C were detected in 10% of patients, while 40% exhibited GUCY2C-specific T-cell responses. GUCY2C-specific responses were exclusively CD8+ cytotoxic T cells, mimicking pre-clinical studies in mice in which GUCY2C-specific CD4+ T cells are eliminated by self-tolerance, while CD8+ T cells escape tolerance and mediate antitumor immunity. Moreover, pre-existing neutralizing antibodies (NAbs) to the Ad5 vector were associated with poor vaccine-induced responses, suggesting that Ad5 NAbs oppose GUCY2C immune responses to the vaccine in patients and supported by mouse studies. Conclusions: Split tolerance to GUCY2C in cancer patients can be exploited to safely generate antigen-specific cytotoxic CD8+, but not autoimmune CD4+, T cells by Ad5-GUCY2C-PADRE in the absence of pre-existing NAbs to the viral vector. TRIAL REGISTRATION: This trial (NCT01972737) was registered at ClinicalTrials.gov on October 30th, 2013. https://clinicaltrials.gov/ct2/show/NCT01972737

    Common snook fed in alternate and continuous regimens with diet supplemented with Bacillus subtilis probiotic.

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    The objective of this work was to evaluate the addition of Bacillus subtilis probiotic to the feed of common snook (Centropomus undecimalis) fingerlings, in alternate and continuous regimens. Six hundred and sixty fish, with verage length of 5.90±0.88 cm and weight of 1.92±0.28g, were stocked in 12 cages of 1.0 m 3 , with 55 fish each. The experimental design was completely randomized, with three treatments and four replicates. The treatments consisted of diet with the addition of probiotic, provided in alternate regimen for 7 days and in continuous regimen; besides a control without probiotic in the feed. Zootechnical performance, body composition, immune response, and blood parameters were evaluated. No significant differences were observed in zootechnical performance indexes and in body composition of fish treated with probiotic, when compared to the control. Fish from the alternate regimen showed an increment in respiratory burst and a lower total erythrocyte count than fish from the continuous regimen and the control. Fish from the continuous regimen did not differ from those of the control. The addition of Bacillus subtilis does not increase growth rates of common snook fingerlings; however, it has an immunostimulant action when supplied in alternate regimen.Título em português: Robalo?flecha alimentado em regimes alternado e contínuo com dieta suplementada com o probiótico Bacillus subtilis

    Why Catastrophic Organizational Failures Happen

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    Excerpt from the introduction: The purpose of this chapter is to examine the major streams of research about catastrophic failures, describing what we have learned about why these failures occur as well as how they can be prevented. The chapter begins by describing the most prominent sociological school of thought with regard to catastrophic failures, namely normal accident theory. That body of thought examines the structure of organizational systems that are most susceptible to catastrophic failures. Then, we turn to several behavioral perspectives on catastrophic failures, assessing a stream of research that has attempted to understand the cognitive, group and organizational processes that develop and unfold over time, leading ultimately to a catastrophic failure. For an understanding of how to prevent such failures, we then assess the literature on high reliability organizations (HRO). These scholars have examined why some complex organizations operating in extremely hazardous conditions manage to remain nearly error free. The chapter closes by assessing how scholars are trying to extend the HRO literature to develop more extensive prescriptions for managers trying to avoid catastrophic failures

    Guanylate cyclase C as a target for prevention, detection, and therapy in colorectal cancer.

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    INTRODUCTION: Colorectal cancer remains the second leading cause of cancer death in the United States, and new strategies to prevent, detect, and treat the disease are needed. The receptor, guanylate cyclase C (GUCY2C), a tumor suppressor expressed by the intestinal epithelium, has emerged as a promising target. Areas covered: This review outlines the role of GUCY2C in tumorigenesis, and steps to translate GUCY2C-targeting schemes to the clinic. Endogenous GUCY2C-activating ligands disappear early in tumorigenesis, silencing its signaling axis and enabling transformation. Pre-clinical models support GUCY2C ligand supplementation as a novel disease prevention paradigm. With the recent FDA approval of the GUCY2C ligand, linaclotide, and two more synthetic ligands in the pipeline, this strategy can be tested in human trials. In addition to primary tumor prevention, we also review immunotherapies targeting GUCY2C expressed by metastatic lesions, and platforms using GUCY2C as a biomarker for detection and patient staging. Expert commentary: Results of the first GUCY2C targeting schemes in patients will become available in the coming years. The identification of GUCY2C ligand loss as a requirement for colorectal tumorigenesis has the potential to change the treatment paradigm from an irreversible disease of genetic mutation, to a treatable disease of ligand insufficiency

    APC-β-catenin-TCF signaling silences the intestinal guanylin-GUCY2C tumor suppressor axis.

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    Sporadic colorectal cancer initiates with mutations in APC or its degradation target β-catenin, producing TCF-dependent nuclear transcription driving tumorigenesis. The intestinal epithelial receptor, GUCY2C, with its canonical paracrine hormone guanylin, regulates homeostatic signaling along the crypt-surface axis opposing tumorigenesis. Here, we reveal that expression of the guanylin hormone, but not the GUCY2C receptor, is lost at the earliest stages of transformation in APC-dependent tumors in humans and mice. Hormone loss, which silences GUCY2C signaling, reflects transcriptional repression mediated by mutant APC-β-catenin-TCF programs in the nucleus. These studies support a pathophysiological model of intestinal tumorigenesis in which mutant APC-β-catenin-TCF transcriptional regulation eliminates guanylin expression at tumor initiation, silencing GUCY2C signaling which, in turn, dysregulates intestinal homeostatic mechanisms contributing to tumor progression. They expand the mechanistic paradigm for colorectal cancer from a disease of irreversible mutations in APC and β-catenin to one of guanylin hormone loss whose replacement, and reconstitution of GUCY2C signaling, could prevent tumorigenesis

    Dispelling the myth of robotic efficiency: why human space exploration will tell us more about the Solar System than will robotic exploration alone

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    There is a widely held view in the astronomical community that unmanned robotic space vehicles are, and will always be, more efficient explorers of planetary surfaces than astronauts (e.g. Coates, 2001; Clements 2009; Rees 2011). Partly this is due to a common assumption that robotic exploration is cheaper than human exploration (although, as we shall see, this isn't necessarily true if like is compared with like), and partly from the expectation that continued developments in technology will relentlessly increase the capability, and reduce the size and cost, of robotic missions to the point that human exploration will not be able to compete. I will argue below that the experience of human exploration during the Apollo missions, more recent field analogue studies, and trends in robotic space exploration actually all point to exactly the opposite conclusion.Comment: 12 pages; 5 figures. Published, with minor modifications, in Astronomy and Geophysics, Vol. 53, pp. 2.22-2.26, 201

    Comparative Visual Function in Predatory Fishes from the Indian River Lagoon

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    Visual temporal resolution and spectral sensitivity of three coastal teleost species (common snook [Centropomus undecimalis], gray snapper [Lutjanus griseus], and pinfish [Lagodon rhomboides]) were investigated by electroretinogram. Temporal resolution was quantified under photopic and scotopic conditions using response waveform dynamics and maximum critical flicker fusion frequency (CFFmax). Photopic CFFmax was significantly higher than scotopic CFFmax in all species. The snapper had the shortest photoreceptor response latency time (26.7 ms) and the highest CFFmax (47 Hz), suggesting that its eyes are adapted for a brighter photic environment. In contrast, the snook had the longest response latency time (36.8 ms) and lowest CFFmax (40 Hz), indicating that its eyes are adapted for a dimmer environment or nocturnal lifestyle. Species spectral responses ranged from 360 to 620 nm and revealed the presence of rods sensitive to dim and twilight conditions, as well as multiple cone visual pigments providing the basis for color and contrast discrimination. Collectively, our results demonstrate differences in visual function among species inhabiting the Indian River Lagoon system, representative of their unique ecology and life histories

    The family trust in New Zealand and the claims of ‘Unwelcome Beneficiaries’

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    In June 2009, at the Transcontinental Trusts conference in Geneva, His Honour Justice David Hayton said that the New Zealand Court of Appeal had got aspects of the law of trusts wrong in its decision in Official Assignee v Wilson [2008] 3 NZLR 45. The Court held that the test for proving a trust was a sham was whether the trustees and settlor had a common intention that the trust was not to be a genuine entitiy. Hayton prefers a more objective approach and looks to the objective effect of a shammer’s conduct and not look for secret dishonest intentions which will hardly ever be revealed. Hayton’s approach would ensure that trust property would be made available to creditors so that they were paid what they were due by declaring the trusts to be shams. Family trusts have become big business in New Zealand and are commonly used to protect a businessman’s assets from creditors. While there is nothing illegal in setting up a family trust, it is my contention that the law pertaining to family trusts in New Zealand has become so far removed from the accepted principles of equity as to demand investigation. This paper explores the origins of equity and compares the modern family trust against the equitable principles which have been developed over hundreds of years, even as far back as Plato’s Greece. The paper links the equity of Ancient Greece to Cicero in Rome, through the early Roman Church to the Chancellors serving English Kings. The law of England leads to the law of modern New Zealand. The paper goes on to examine the way the family trust has been used to defeat the legitimate claims of creditors. I aim to show that the approach taken by the New Zealand Court of Appeal is too narrow and favours the ‘shamming’ settlor at the expense of creditors who have given good consideration in comparison with volunteer beneficiaries. Moreover the family trust has become a mechanism that bears little relationship to recognised equitable principles and should lose the protection accorded to properly constituted trusts
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