477 research outputs found

    Potential economic benefits of eliminating canine rabies

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    Contents 1. Introduction ...................352 2. Pathways to economic impacts .................353 3. Counting the costs of canine rabies ...........353 3.1. Direct costs ...............................353 3.2. Indirect costs ............................353 3.3. Comparing regions ...................353 4. Monetizing the impacts ..............354 5. Macroeconomic impacts ..................355 6. The value of global canine rabies elimination .........355 References ..............................35

    Cholesterol ester accumulation: An immediate consequence of acute in vivo ischemic renal injury

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    Cholesterol ester accumulation: An immediate consequence of acute in vivo ischemic renal injury.BackgroundCholesterol is a major constituent of plasma membranes, and recent evidence indicates that it is up-regulated during the maintenance phase of acute renal failure (ARF). However, cholesterol's fate and that of the cholesterol ester (CE) cycle [shuttling between free cholesterol (FC) and CEs] during the induction phase of ARF have not been well defined. The present studies sought to provide initial insights into these issues.MethodsFC and CE were measured in mouse renal cortex after in vivo ischemia (15 and 45 minutes)/reperfusion (0 to 120 minutes) and glycerol-induced myoglobinuria (1 to 2 hours). FC/CE were also measured in (1) cultured human proximal tubule (HK-2) cells three hours after ATP depletion and in (2) isolated mouse proximal tubule segments (PTSs) subjected to plasma membrane damage (with cholesterol oxidase, sphingomyelinase, phospholipase A2, or cytoskeletal disruption with cytochalasin B). The impact of cholesterol synthesis inhibition (with mevastatin) and FC traffic blockade (with progesterone) on injury-evoked FC/CE changes was also assessed.ResultsIn vivo ischemia caused approximately threefold to fourfold CE elevations, but not FC elevations, that persisted for at least two hours of reperfusion. Conversely, myoglobinuria had no effect. Isolated CE increments were observed in ATP-depleted HK-2 cells. Neither mevastatin nor progesterone blocked this CE accumulation. Plasma membrane injury induced with sphingomyelinase or cholesterol oxidase, but not with phospholipase A2 or cytochalasin B, increased tubule CE content. High CE levels, induced with cholesterol oxidase, partially blocked hypoxic PTS attack.ConclusionsIn vivo ischemia/reperfusion acutely increases renal cortical CE, but not FC, content, indicating perturbed CE/FC cycling. The available data suggest that this could stem from specific types of plasma membrane damage, which then increase FC flux via aberrant pathways to the endoplasmic reticulum, where CE formation occurs. That CE levels are known to inversely correlate with both renal and nonrenal cell injury suggests the potential relevance of these observations to the induction phase of ischemic ARF

    Polyphenon E enhances the antitumor immune response in neuroblastoma by inactivating myeloid suppressor cells

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    This is the author's accepted manuscript. The final published article is available from the link below. Note: In this manuscript as well as in the original published version of this article the word "Polyphenon" was incorrectly spelled in the title as "Polyphenol."Purpose: Neuroblastoma is a rare childhood cancer whose high risk, metastatic form has a dismal outcome in spite of aggressive therapeutic interventions. The toxicity of drug treatments is a major problem in this pediatric setting. In this study, we investigated whether Polyphenon E, a clinical grade mixture of green tea catechins under evaluation in multiple clinical cancer trials run by the National Cancer Institute (Bethesda, MD), has anticancer activity in mouse models of neuroblastoma. Experimental Design: We used three neuroblastoma models: (i) transgenic TH-MYCN mouse developing spontaneous neuroblastomas; (ii) nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice xenotransplanted with human SHSY5Y cells; and (iii) A/J mice transplanted with syngeneic Neuro 2A cells. Mice were randomized in control and Polyphenon E–drinking groups. Blood from patients with neuroblastoma and normal controls was used to assess the phenotype and function of myeloid cells. Results: Polyphenon E reduced the number of tumor-infiltrating myeloid cells, and inhibited the development of spontaneous neuroblastomas in TH-MYCN transgenic mice. In therapeutic models of neuroblastoma in A/J, but not in immunodeficient NOD/SCID mice, Polyphenon E inhibited tumor growth by acting on myeloid-derived suppressor cells (MDSC) and CD8 T cells. In vitro, Polyphenon E impaired the development and motility of MDSCs and promoted differentiation to more neutrophilic forms through the 67 kDa laminin receptor signaling and induction of granulocyte colony-stimulating factor. The proliferation of T cells infiltrating a patient metastasis was reactivated by Polyphenon E. Conclusions: These findings suggest that the neuroblastoma-promoting activity of MDSCs can be manipulated pharmacologically in vivo and that green tea catechins operate, at least in part, through this mechanism.SPARKS, Research in Childhood Cancer, the CGD Research Trust, and the Wellcome Trust

    Measuring the learning effectiveness of serious gaming for training of complex manufacturing tasks

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    © 2017, © The Author(s) 2017. Background. Training new workers on complex manufacturing tasks has long been a challenge for high value manufacturing companies. Equipment downtime, costly instructors, and dangerous working environments are some of the impediments of hands-on training. To overcome these hurdles, a traditional manufacturing paper manual was transformed into a serious game through capturing and embedding expert knowledge. Aim. This article investigates the learning effectiveness of learning via a serious game (Training Game) compared with the tradition learning method (Paper Manual) through a user study. Method. Twenty employees took part in a randomised controlled trial. They were assigned to one of two conditions: Training Game (experimental condition), or Paper Manual (control condition). Participants spent a maximum of 30 minutes to study manufacturing instructions before completing two tests to evaluate the amount of learning achieved. Results. The results show that the Training Game was more effective for learning procedu ral knowledge than the Paper Manual. Regarding factual knowledge, no significant difference was identified between the two conditions. In terms of motivation, increased engagement levels were reported in the Training Game condition. Conclusions. This user study shows evidence that the serious TG being evaluated is an effective method for training procedural knowledge in a complex manufacturing scenario

    Agricultural and food security impacts from the 2010 Russia flash drought

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    The flash drought and its associated heat wave that affected western Russia in the summer of 2010 had significant cascading agricultural and socioeconomic impacts. Drought indicators sensitive to soil moisture and evapotranspiration (ET) showed that the flash drought began in June 2010, then intensified rapidly and expanded to cover much of western Russia. By early July, almost all of the major wheat producing regions of Russia were experiencing extreme water stress to the winter and spring wheat crops. The timing of the onset of the flash drought was particularly devastating as the period of most rapid intensification overlapped with the flowering stage for both the winter and spring wheat crops. As a result, wheat yields in Russia were reduced by over 70 percent in top wheat producing oblasts and total wheat production was reduced by 20 million metric tons (MT) compared to the previous seasons. In fulfillment of its recently adopted Food Security Doctrine, the Russian government banned the export of wheat in early August 2010 to preserve wheat for its own consumption. Further compounding matters on a global scale, the significant reduction in wheat production in Russia coincided with wheat production issues in places like western Australia, which led to a large drop in global wheat stocks. The sharp drop in global wheat stocks coincided with a rapid increase in wheat prices across the globe. The rapid increase in wheat prices, partly resulting from the rapid intensification of drought in Russia, led to increased prices for wheat flour and bread in many countries throughout the world. This ultimately led to an increase in poverty and civil unrest in countries like Mozambique and Egypt with a history of inequality and poverty

    Light Curves and Period Changes of Type II Cepheids in the Globular Clusters M3 and M5

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    Light curves in the B, V, and I_c passbands have been obtained for the type II Cepheids V154 in M3 and V42 and V84 in M5. Alternating cycle behavior, similar to that seen among RV Tauri variables, is confirmed for V84. Old and new observations, spanning more than a century, show that V154 has increased in period while V42 has decreased in period. V84, on the other hand, has shown large, erratic changes in period that do not appear to reflect the long term evolution of V84 through the HR diagram.Comment: 28 pages, 12 figure

    Effects of Long-Term Pioglitazone Treatment on Peripheral and Central Markers of Aging

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    BACKGROUND: Thiazolidinediones (TZDs) activate peroxisome proliferator-activated receptor gamma (PPARgamma) and are used clinically to help restore peripheral insulin sensitivity in Type 2 diabetes (T2DM). Interestingly, long-term treatment of mouse models of Alzheimer\u27s disease (AD) with TZDs also has been shown to reduce several well-established brain biomarkers of AD including inflammation, oxidative stress and Abeta accumulation. While TZD\u27s actions in AD models help to elucidate the mechanisms underlying their potentially beneficial effects in AD patients, little is known about the functional consequences of TZDs in animal models of normal aging. Because aging is a common risk factor for both AD and T2DM, we investigated whether the TZD, pioglitazone could alter brain aging under non-pathological conditions. METHODS AND FINDINGS: We used the F344 rat model of aging, and monitored behavioral, electrophysiological, and molecular variables to assess the effects of pioglitazone (PIO-Actos® a TZD) on several peripheral (blood and liver) and central (hippocampal) biomarkers of aging. Starting at 3 months or 17 months of age, male rats were treated for 4-5 months with either a control or a PIO-containing diet (final dose approximately 2.3 mg/kg body weight/day). A significant reduction in the Ca2+-dependent afterhyperpolarization was seen in the aged animals, with no significant change in long-term potentiation maintenance or learning and memory performance. Blood insulin levels were unchanged with age, but significantly reduced by PIO. Finally, a combination of microarray analyses on hippocampal tissue and serum-based multiplex cytokine assays revealed that age-dependent inflammatory increases were not reversed by PIO. CONCLUSIONS: While current research efforts continue to identify the underlying processes responsible for the progressive decline in cognitive function seen during normal aging, available medical treatments are still very limited. Because TZDs have been shown to have benefits in age-related conditions such as T2DM and AD, our study was aimed at elucidating PIO\u27s potentially beneficial actions in normal aging. Using a clinically-relevant dose and delivery method, long-term PIO treatment was able to blunt several indices of aging but apparently affected neither age-related cognitive decline nor peripheral/central age-related increases in inflammatory signaling
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