251 research outputs found

    Crowding –Out and Fundraising Efforts: The impact of government grants on Symphony Orchestras

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    The crowding-out of private donations by government grants is an integral element in designing an efficient method of financing nonprofit activity. This paper looks at elements of crowd-out, both the direct impact on donors and the indirect impact due to the response of nonprofits. We include both a theoretical and empirical analysis of the reactions by donors and nonprofits to an increase in government funding based on data from the League of American Orchestras’ annual reports from 2004-2007. To combat indirect crowd-out, renewed emphasis should be placed on grant design; for direct crowd-out, theories of collective action are appropriate

    In My View

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    Three-dimensional observations of an aperiodic oscillatory gliding behavior in Myxococcus xanthus using confocal interference reflection microscopy

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    The deltaproteobacterium Myxococcus xanthus is a model for bacterial motility and has provided unprecedented insights into bacterial swarming behaviors. Fluorescence microscopy techniques have been invaluable in defining the mechanisms that are involved in gliding motility, but these have almost entirely been limited to two-dimensional (2D) studies, and there is currently no understanding of gliding motility in a three-dimensional (3D) context. We present here the first use of confocal interference reflection microscopy (IRM) to study gliding bacteria, revealing aperiodic oscillatory behavior with changes in the position of the basal membrane relative to the substrate on the order of 90 nm in vitro. First, we use a model planoconvex lens specimen to show how topological information can be obtained from the wavelength-dependent interference pattern in IRM. We then use IRM to observe gliding M. xanthus bacteria and show that cells undergo previously unobserved changes in their adhesion profile as they glide. We compare the wild type with mutants that have reduced motility, which also exhibit the same changes in the adhesion profile during gliding. We find that the general gliding behavior is independent of the proton motive force-generating complex AglRQS and suggest that the novel behavior that we present here may be a result of recoil and force transmission along the length of the cell body following firing of the type IV pili. IMPORTANCE 3D imaging of live bacteria with optical microscopy techniques is a challenge due to the small size of bacterial cells, meaning that previous studies have been limited to observing motility behavior in 2D. We introduce the application of confocal multiwavelength interference reflection microscopy to bacteria, which enables visualization of 3D motility behaviors in a single 2D image. Using the model organism Myxococcus xanthus, we identified novel motility behaviors that are not explained by current motility models, where gliding bacteria exhibit aperiodic changes in their adhesion to an underlying solid surface. We concluded that the 3D behavior was not linked to canonical motility mechanisms and that IRM could be applied to study a range of microbiological specimens with minimal adaptation to a commercial microscope

    QTL Mapping of a High Protein Digestibility Trait in Sorghum bicolor

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    Compared with other cereal grains, Sorghum bicolor shows lower protein digestibility. The low digestibility is thought to result from disulfide cross linking in the β- and γ-kafirins. In contrast, the single recessive high digestibility/high lysine content (HD) mutation which confers greater grain digestibility exists in sorghum that is thought to result from reduced accumulation of γ-kafirin that allows greater access to the high digestible α-kafarin fraction. In an effort to both clearly define the molecular basis for the HD trait and develop tools to improve the introgression of this difficult-to-screen trait, this study focuses on mapping the QTLs linked to this trait. While the HD trait has been defined as a single recessive gene, our results uncovered that two major QTLs on chromosome 1 are associated with protein digestibility—one QTL (locus 1 from the HD parent) unfavorably affects digestibility and one QTL (locus 2 from the HD parent) only 20 cM away favorably affects digestibility. A contrast analysis between genotypic groups at these two loci shows that a higher level of protein digestibility may be obtained when this linkage in repulsion is broken and favorable alleles are allowed to recombine

    Weekly and daily tooth brushing by care staff reduces gingivitis and calculus in racing greyhounds

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    SIMPLE SUMMARY: Dental disease affects many dogs worldwide and is believed to be particularly problematic for racing greyhounds. It costs the industry and rehoming charities financially and likely causes unnecessary suffering to a large number of dogs. The risk factors for dental disease in this population are debated, and the best methods to overcome it are relatively unresearched. We carried out a trial in which 160 racing greyhounds were divided into three groups. The staff looking after them either brushed their teeth daily, weekly or never, for a period of two months. An experimenter measured the dog’s level of calculus (hardened dental plaque) and gingivitis (gum inflammation) at the start, and again after two months. We found that both weekly and daily brushing resulted in significant reductions in calculus, but for gingivitis only daily brushing resulted in a significant reduction. The effects, however, were not noticeable on the front incisor teeth. Since the staff implementing the routine reported a minimal time commitment and positive experiences, we suggest that daily brushing is recommended for racing greyhounds, and that emphasis is placed on brushing all teeth groups. Similar trials need to be conducted with retired greyhounds since these have been shown to present particularly high levels of periodontal disease. ABSTRACT: Periodontal disease is one of the most common conditions affecting dogs worldwide and is reported to be particularly prevalent in racing greyhounds. A range of potential risk factors have been hypothesised. Previous research has suggested that regular tooth brushing can reduce both calculus and gingivitis, but the frequency required is unclear. Here, we report a controlled blinded in situ trial, in which kennel staff brushed 160 racing greyhounds’ teeth (living at six kennel establishments), either weekly, daily or never over a two-month period. All of the visible teeth were scored for calculus and gingivitis, using previously validated scales. We calculated average scores for each of the three teeth groups and overall whole mouth scores, averaging the teeth groups. Changes were compared to the baseline. After two months, the total calculus scores (controlling for baseline) were significantly different in the three treatment groups, (F((2,129)) = 10.76, p < 0.001) with both weekly and daily brushing resulting in significant reductions. Gingivitis was also significantly different between groups (F((2,128)) = 4.57, p = 0.012), but in this case, only daily brushing resulted in a significant reduction. Although the dogs in different kennels varied significantly in their levels of both calculus (F((5,129)) = 8.64, p < 0.001) and gingivitis (F((5,128)) = 3.51 p = 0.005), the intervention was similarly effective in all of the establishments. The teeth groups varied, and the incisors were not significantly affected by the treatment. Since the trainers implementing the routine, reported a minimal time commitment and positive experiences, we suggest that daily brushing is recommended for racing greyhounds, and that any instructions or demonstrations should include attention to all teeth groups including the incisors. Similar trials need to be conducted with retired greyhounds since these have been shown to present particularly high levels of periodontal disease

    The CATFISH study protocol: an evaluation of a water fluoridation scheme

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    Abstract Background Tooth decay is the commonest disease of childhood. We have known for over 90 years that fluoride can prevent tooth decay; it is present in nearly all toothpastes and can be provided in mouthwashes, gels and varnishes. The oldest method of applying fluoride is via the water supply at a concentration of 1 part per million. The two most important reviews of water fluoridation in the United Kingdom (the York Review and MRC Report on water fluoridation and health) concluded that whilst there was evidence to suggest water fluoridation provided a benefit in caries reduction, there was a need to improve the evidence base in several areas. Methods/Design This study will use a natural experiment to assess the incidence of caries in two geographical areas, one in which the water supply is returned to being fluoridated following a discontinuation of fluoridation and one that continues to have a non-fluoridated water supply. The oral health of two discrete study populations will be evaluated - those born 9 months after the water fluoridation was introduced, and those who were in their 1st year of school after the introduction of fluoridated water. Both populations will be followed prospectively for 5 years using a census approach in the exposed group along with matched numbers recruitment in a non-exposed control. Parents of the younger cohort will complete questionnaires every 6 months with child clinical examination at ages 3 and 5, whilst the older cohort will have clinical examinations only, at approximately 5, 7 and 11 years old. Discussion This project provides a unique opportunity to conduct a high quality evaluation of the reintroduction of a water fluoridation scheme, which satisfies the inclusion criteria stipulated by the York systematic review and can address the design issues identified in the MRC report. The research will make a major contribution to the understanding of the costs and effects of water fluoridation in the UK in the 21st Century. Its findings will help inform UK policy on this important public health intervention and may have a significant impact on public health policy in other developed countries. There is currently true equipoise in relation to the effectiveness of water fluoridation in contemporary populations and while the biological plausibility is well established, there is a need to examine impact on the changing epidemiological status of dental decay

    Addressing multi-scale microbial challenges using the Mesolens

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    We provide a brief review of the development and application of the Mesolens and its impact on microbiology. Microbial specimens such as infected tissue samples, colonies surfaces, and biofilms are routinely collected at the mesoscale. This means that they are relatively large multi-millimetre-sized samples which contain microscopic detail that must be observed to answer important questions across various sectors. The Mesolens presents the ideal imaging method to study these specimens as no other optical microscope can thanks to its unique combination of low magnification and high numerical aperture providing large field-of-view, high-resolution imaging. We demonstrate the current applications of the Mesolens to microbial imaging and go on to outline the huge potential of the Mesolens to impact other key areas of microbiology

    Flying Squirrel–associated Typhus, United States

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    In March 2002, typhus fever was diagnosed in two patients residing in West Virginia and Georgia. Both patients were hospitalized with severe febrile illnesses, and both had been recently exposed to or had physical contact with flying squirrels or flying squirrel nests. Laboratory results indicated Rickettsia prowazekii infection

    Comparison of baricitinib, upadacitinib, and tofacitinib mediated regulation of cytokine signaling in human leukocyte subpopulations

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    BACKGROUND: The in vitro pharmacology of baricitinib, upadacitinib, and tofacitinib was evaluated to understand differences among these JAK inhibitors (JAKis) at the cellular level. METHODS: Peripheral blood mononuclear cells from healthy donors were incubated with different JAKis, levels of phosphorylated signal transducer and activator of transcription (pSTAT) were measured following cytokine stimulation, and half maximum inhibitory concentration (IC50) values were calculated in phenotypically gated leukocyte subpopulations. Therapeutic dose relevance of the in vitro analysis was assessed using calculated mean concentration-time profiles over 24 h obtained from JAKi-treated subjects. Time above IC50 and average daily percent inhibition of pSTAT formation were calculated for each JAKi, cytokine, and cell type. RESULTS: Distinct JAKis displayed different in vitro pharmacologic profiles. For example, tofacitinib and upadacitinib were the most potent inhibitors of the JAK1/3-dependent cytokines tested (interleukin [IL]-2, IL-4, IL-15, and IL-21) with lower IC50 values and increased time above IC50 translating to a greater overall inhibition of STAT signaling during the dosing interval. All JAKis tested inhibited JAK1/2-dependent cytokines (e.g., IL-6 and interferon [IFN]-γ), the JAK1/tyrosine kinase 2 (TYK2)-dependent cytokines IL-10 and IFN-α, the JAK2/2-dependent cytokines IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), and the JAK2/TYK2-dependent cytokine granulocyte colony-stimulating factor (G-CSF), but often to significantly differing degrees. CONCLUSIONS: Different JAKis modulated distinct cytokine pathways to varying degrees, and no agent potently or continuously inhibited an individual cytokine signaling pathway throughout the dosing interval. Notably, baricitinib inhibited JAK1/3 signaling to a lesser extent than upadacitinib and tofacitinib, while upadacitinib, baricitinib, and tofacitinib inhibited the signaling of JAK2/2-dependent cytokines, including GM-CSF and IL-3, as well as the signaling of the JAK2/TYK2-dependent cytokine G-CSF
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