94 research outputs found
Keeping the Freedom to Include: Teachers Navigating “Pushback” and Marshalling “Backup” to Keep Inclusion on the Agenda
Abstract: This paper shares K12 educators’ efforts to marshal local support for the act of basic inclusion: welcoming all communities as equally valuable. We share data from a national pilot of #USvsHate (usvshate.org), an educator- and student-led “anti-hate” messaging project. In interviews, participating educators revealed careers of “pushback” against even their basic efforts to include (mention or empathize with) marginalized populations. They also shared five key forms of “backup” they had learned to marshal to keep such topics on the agenda. Building on scholarship positioning basic and deeper inclusion work as the unarguable task of schools, we explore how keeping the freedom to undertake even basic inclusion efforts requires teachers to preserve agency through assembling local backup -- supports from other people
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Microstructure and mechanical properties of plasma spraying coatings from YSZ feedstocks comprising nano- and submicron-sized particles
Atmospheric plasma spraying (APS) is an attractive technique to obtain nanostructured coatings due to its versatility, simplicity and relatively low cost. However, nanoparticles cannot be fed into the plasma using conventional feeding systems, due to their low mass and poor flowability, and must be adequately reconstituted into sprayable micrometric agglomerates.
In this work, nanostructured and submicron/nanostiuctured powders of yttria-stabilised zirconia (YSZ) were deposited using APS, with a view to obtaining high-performance thermal bather coatings (IBC). All powders were reconstituted by spray-drying from different solid loading suspensions, followed by a thermal treatment of the spray-dried granules to reduce agglomerate porosity and enhance powder sinterability. The reconstituted granules were characterised by XRD, SEM, pore sizing and flowability evaluation.
The reconstituted feedstocks were successfully deposited onto metallic substrates by APS. A metallic bond coat was sprayed between the substrate and the ceramic layer. The coating microstructure, characterised by SEM, was formed by partially melted zones, which retained the initial powder microstructure, embedded in a fully melted matrix which acts as a binder. It was shown that feedstock characteristics which in turn are very dependent of starting suspension characteristics, in particular agglomerate density and primary particle size, impact on coating microstructure (porosity and amount of partially-melted areas). For this reason mechanical properties of coatings are also strongly affected by feeding powder characteristics. (C) 2014 Elsevier Ltd and Techna Group S.r.l. All rights reserved.This work has been supported by the Spanish Ministry of Economy and Competitiveness (project MAT2012-38364-C03), by the Research Promotion Plan of the Universitat Jaume I, action 3.1 (ref. PREDOC/2009/10) and it has been co-funded by ERDF (European Regional Development Funds). The authors also acknowledge the SCIC of Valencia University for the FEG-SEM observations. Finally the Spanish Ministry of Science and Innovation for Juan de la Cierva contract (JCI-2011-10498) is also grateful.Carpio, P.; Borrell Tomás, MA.; Salvador Moya, MD.; Gómez, A.; Martínez, E.; Sánchez, E. (2015). Microstructure and mechanical properties of plasma spraying coatings from YSZ feedstocks comprising nano- and submicron-sized particles. Ceramics International. 41(3, Part A):4108-4117. https://doi.org/10.1016/j.ceramint.2014.11.106S41084117413, Part
MARTX Toxin in the Zoonotic Serovar of Vibrio vulnificus Triggers an Early Cytokine Storm in Mice
Vibrio vulnificus biotype 2-serovar E is a zoonotic clonal complex that can cause death by sepsis in humans and fish. Unlike other biotypes, Bt2 produces a unique type of MARTXVv (Multifunctional-Autoprocessive-Repeats-in-Toxin; RtxA13), which is encoded by a gene duplicated in the pVvBt2 plasmid and chromosome II. In this work, we analyzed the activity of this toxin and its role in human sepsis by performing in vitro, ex vivo, and in vivo assays. First, we demonstrated that the ACD domain, present exclusively in this toxin variant, effectively has an actin-cross-linking activity. Second, we determined that the whole toxin caused death of human endotheliocytes and monocytes by lysis and apoptosis, respectively. Finally, we tested the hypothesis that RtxA13 contributes to human death caused by this zoonotic serovar by triggering an early cytokine storm in blood. To this end, we used a Bt2-SerE strain (R99) together with its rtxA13 deficient mutant, and a Bt1 strain (YJ016) producing RtxA11 (the most studied MARTXVv) together with its rtxA11 deficient mutant, as controls. Our results showed that RtxA13 was essential for virulence, as R99ΔΔrtxA13 was completely avirulent in our murine model of infection, and that R99, but not strain YJ016, induced an early, strong and dysregulated immune response involving the up-regulation of a high number of genes. This dysregulated immune response was directly linked to RtxA13. Based on these results and those obtained ex vivo (human blood), we propose a model of infection for the zoonotic serovar of V. vulnificus, in which RtxA13 would act as a sepsis-inducing toxin
Subtelomeric assembly of a multi-gene pathway for antimicrobial defense compounds in cereals
Non-random gene organization in eukaryotes plays a significant role in genome evolution. Here, we investigate the origin of a biosynthetic gene cluster for production of defence compounds in oat—the avenacin cluster. We elucidate the structure and organisation of this 12-gene cluster, characterise the last two missing pathway steps, and reconstitute the entire pathway in tobacco by transient expression. We show that the cluster has formed de novo since the divergence of oats in a subtelomeric region of the genome that lacks homology with other grasses, and that gene order is approximately colinear with the biosynthetic pathway. We speculate that the positioning of the late pathway genes furthest away from the telomere may mitigate against a ‘self-poisoning’ scenario in which toxic intermediates accumulate as a result of telomeric gene deletions. Our investigations reveal a striking example of adaptive evolution underpinned by remarkable genome plasticity
Validation of Plasmodium falciparum dUTPase as the target of 5'-tritylated deoxyuridine analogues with anti-malarial activity
BACKGROUND: Malaria remains as a major global problem, being one of the infectious diseases that engender highest mortality across the world. Due to the appearance of resistance and the lack of an effective vaccine, the search of novel anti-malarials is required. Deoxyuridine 5'-triphosphate nucleotido-hydrolase (dUTPase) is responsible for the hydrolysis of dUTP to dUMP within the parasite and has been proposed as an essential step in pyrimidine metabolism by providing dUMP for thymidylate biosynthesis. In this work, efforts to validate dUTPase as a drug target in Plasmodium falciparum are reported. METHODS: To investigate the role of PfdUTPase in cell survival different strategies to generate knockout mutants were used. For validation of PfdUTPase as the intracellular target of four inhibitors of the enzyme, mutants overexpressing PfdUTPase and HsdUTPase were created and the IC50 for each cell line with each compound was determined. The effect of these compounds on dUTP and dTTP levels from P. falciparum was measured using a DNA polymerase assay. Detailed localization studies by indirect immunofluorescence microscopy and live cell imaging were also performed using a cell line overexpressing a Pfdut-GFP fusion protein. RESULTS:Different attempts of disruption of the dut gene of P. falciparum were unsuccessful while a 3' replacement construct could recombine correctly in the locus suggesting that the enzyme is essential. The four 5'-tritylated deoxyuridine analogues described are potent inhibitors of the P. falciparum dUTPase and exhibit antiplasmodial activity. Overexpression of the Plasmodium and human enzymes conferred resistance against selective compounds, providing chemical validation of the target and confirming that indeed dUTPase inhibition is involved in anti-malarial activity. In addition, incubation with these inhibitors was associated with a depletion of the dTTP pool corroborating the central role of dUTPase in dTTP synthesis. PfdUTPase is mainly localized in the cytosol. CONCLUSION: These results strongly confirm the pivotal and essential role of dUTPase in pyrimidine biosynthesis of P. falciparum intraerythrocytic stages
Providing baseline data for conservation–Heart rate monitoring in captive scimitar-horned oryx
Heart rate biologging has been successfully used to study wildlife responses to natural and human-caused stressors (e.g., hunting, landscape of fear). Although rarely deployed to inform conservation, heart rate biologging may be particularly valuable for assessing success in wildlife reintroductions. We conducted a case study for testing and validating the use of subcutaneous heart rate monitors in eight captive scimitar-horned oryx (Oryx dammah), a once-extinct species that is currently being restored to the wild. We evaluated biologger safety and accuracy while collecting long-term baseline data and assessing factors explaining variation in heart rate. None of the biologgers were rejected after implantation, with successful data capture for 16–21 months. Heart rate detection accuracy was high (83%–99%) for six of the individuals with left lateral placement of the biologgers. We excluded data from two individuals with a right lateral placement because accuracies were below 60%. Average heart rate for the six scimitar-horned oryx was 60.3 ± 12.7 bpm, and varied by about 12 bpm between individuals, with a minimum of 31 bpm and a maximum of 188 bpm across individuals. Scimitar-horned oryx displayed distinct circadian rhythms in heart rate and activity. Heart rate and activity were low early in the morning and peaked near dusk. Circadian rhythm in heart rate and activity were relatively unchanged across season, but hourly averages for heart rate and activity were higher in spring and summer, respectively. Variation in hourly heart rate averages was best explained by a combination of activity, hour, astronomical season, ambient temperature, and an interaction term for hour and season. Increases in activity appeared to result in the largest changes in heart rate. We concluded that biologgers are safe and accurate and can be deployed in free-ranging and reintroduced scimitar-horned oryx. In addition to current monitoring practices of reintroduced scimitar-horned oryx, the resulting biologging data could significantly aid in 1) evaluating care and management action prior to release, 2) characterizing different animal personalities and how these might affect reintroduction outcomes for individual animals, and 3) identifying stressors after release to determine their timing, duration, and impact on released animals. Heart rate monitoring in released scimitar-horned oryx may also aid in advancing our knowledge about how desert ungulates adapt to extreme environmental variation in their habitats (e.g., heat, drought)
Patient preferences and treatment safety for uncomplicated vulvovaginal candidiasis in primary health care
<p>Abstract</p> <p>Background</p> <p>Vaginitis is a common complaint in primary care. In uncomplicated candidal vaginitis, there are no differences in effectiveness between oral or vaginal treatment. Some studies describe that the preferred treatment is the oral one, but a Cochrane's review points out inconsistencies associated with the report of the preferred way that limit the use of such data. Risk factors associated with recurrent vulvovaginal candidiasis still remain controversial.</p> <p>Methods/Design</p> <p>This work describes a protocol of a multicentric prospective observational study with one year follow up, to describe the women's reasons and preferences to choose the way of administration (oral vs topical) in the treatment of not complicated candidal vaginitis. The number of women required is 765, they are chosen by consecutive sampling. All of whom are aged 16 and over with vaginal discharge and/or vaginal pruritus, diagnosed with not complicated vulvovaginitis in Primary Care in Madrid.</p> <p>The main outcome variable is the preferences of the patients in treatment choice; secondary outcome variables are time to symptoms relief and adverse reactions and the frequency of recurrent vulvovaginitis and the risk factors. In the statistical analysis, for the main objective will be descriptive for each of the variables, bivariant analysis and multivariate analysis (logistic regression).. The dependent variable being the type of treatment chosen (oral or topical) and the independent, the variables that after bivariant analysis, have been associated to the treatment preference.</p> <p>Discussion</p> <p>Clinical decisions, recommendations, and practice guidelines must not only attend to the best available evidence, but also to the values and preferences of the informed patient.</p
Myc and cell cycle control
Soon after the discovery of the Myc gene (c-Myc), it became clear thatMyc expression levels tightly correlate to cell proliferation. The entry in cell cycle of quiescent cells upon Myc enforced expression has been described in manymodels. Also, the downregulation or inactivation ofMyc results in the impairment of cell cycle progression. Given the frequent deregulation of Myc oncogene in human cancer it is important to dissect out the mechanisms underlying the role ofMyc on cell cycle control. Several parallel mechanisms account forMyc-mediated stimulation of the cell cycle. First,most of the critical positive cell cycle regulators are encoded by genes induced byMyc. These Myc target genes include Cdks, cyclins and E2F transcription factors. Apart from its direct effects on the transcription, Myc is able to hyperactivate cyclin/Cdk complexes through the induction of Cdk activating kinase (CAK) and Cdc25 phosphatases. Moreover, Myc antagonizes the activity of cell cycle inhibitors as p21 and p27 through different mechanisms. Thus, Myc is able to block p21 transcription or to induce Skp2, a protein involved in p27 degradation. Finally, Myc induces DNA replication by binding to replication origins and by upregulating genes encoding proteins required for replication initiation. Myc also regulates genes involved in the mitotic control. A promising approach to treat tumors with deregulated Myc is the synthetic lethality based on the inhibition of Cdks. Thus, the knowledge of the Myc-dependent cell cycle regulatory mechanisms will help to discover new therapeutic approaches directed against malignancies with deregulated Myc. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology.The work in the laboratory of the authors is funded by grants SAF11-23796 from
Spanish Ministry of Industry and Innovation, and ISCIII-RETIC RD12/0036/0033 from Spanish
Ministry of Health to JL, and FIS 11/00397 to MDD. GB is recipient of a fellowship form the FPI
Program. We apologize to colleagues whose work has not been cited in the form of their original
papers but in reviews and whose work has not been discussed due to space limitations or
unintentional omission
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