889 research outputs found

    Herbert J. Seligmann, A Woman in Flower

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    Herbert J. Seligmann writes about Georgia O\u27Keeffe\u27s painting and artistic talent. He compares her work to Alfred Stieglitz\u27s 1925 Exhibition of Seven Americans in the Equivalents.https://egrove.olemiss.edu/creekmore/1000/thumbnail.jp

    Retirement Saving and Decumulation in a Persistent Low-Return Environment

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    Recent economic conditions have vastly changed the retirement landscape as a lengthy period of low interest rates have made building wealth for retirement harder and the risk of depleting wealth during the decumulation phase of retirement greater than at any time in recent history. The retirement environment presents challenges, over (i) the period for which interest rate remain low, and (ii) once interest rates appreciably increase--as fixed income assets then decrease in value. This paper addresses two related topics: first, how have households responded to the current low interest rate environment and second, are there alternative responses or investments which households might do well to consider? Beginning with the first topic: we employ the HRS to first investigate impacts of the 2008 – 2014 low interest rate impacts on savings, wealth and asset allocation both ahead of and while in retirement. As well as employing a full sample we report on the responses of the subset of households who have been relatively successful at building and preserving wealth over this period. Following this analytic work we consider alternative portfolio and wealth management strategies targeting increases in equities and delayed participation in Social Security in terms of their potential to add value in persistent low return environments

    Evolutionary flexibility in routes to mat formation by Pseudomonas

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    Abstract Many bacteria form mats at the air-liquid interface of static microcosms. These structures typically involve the secretion of exopolysaccharides, the production of which is often controlled by the secondary messenger c-di-GMP. Mechanisms of mat formation have been particularly well characterized in Pseudomonas fluorescens SBW25; stimuli or mutations that increase c-di-GMP production by diguanylate cyclases (WspR, AwsR, and MwsR) result in the secretion of cellulose and mat formation. Here, we characterize and compare mat formation in two close relatives of SBW25: Pseudomonas simiae PICF7 and P. fluorescens A506. We find that PICF7?the strain more closely related to SBW25?can form mats through mutations affecting the activity of the same three diguanylate cyclases as SBW25. However, instead of cellulose, these mutations activate production of the exopolysaccharide Pel. We also provide evidence for at least two further?as yet uncharacterized?routes to mat formation by PICF7. P. fluorescens A506, while retaining the same mutational routes to mat formation as SBW25 and PICF7, preferentially forms mats by a semi-heritable mechanism that culminates in Psl and Pga over-production. Our results demonstrate a high level of evolutionary flexibility in the molecular and structural routes to mat formation, even among close relatives

    Relationship between mRNA secondary structure and sequence variability in Chloroplast genes: possible life history implications

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    <p>Abstract</p> <p>Background</p> <p>Synonymous sites are freer to vary because of redundancy in genetic code. Messenger RNA secondary structure restricts this freedom, as revealed by previous findings in mitochondrial genes that mutations at third codon position nucleotides in helices are more selected against than those in loops. This motivated us to explore the constraints imposed by mRNA secondary structure on evolutionary variability at all codon positions in general, in chloroplast systems.</p> <p>Results</p> <p>We found that the evolutionary variability and intrinsic secondary structure stability of these sequences share an inverse relationship. Simulations of most likely single nucleotide evolution in <it>Psilotum nudum </it>and <it>Nephroselmis olivacea </it>mRNAs, indicate that helix-forming propensities of mutated mRNAs are greater than those of the natural mRNAs for short sequences and vice-versa for long sequences. Moreover, helix-forming propensity estimated by the percentage of total mRNA in helices increases gradually with mRNA length, saturating beyond 1000 nucleotides. Protection levels of functionally important sites vary across plants and proteins: <it>r</it>-strategists minimize mutation costs in large genes; <it>K</it>-strategists do the opposite.</p> <p>Conclusion</p> <p>Mrna length presumably predisposes shorter mRNAs to evolve under different constraints than longer mRNAs. The positive correlation between secondary structure protection and functional importance of sites suggests that some sites might be conserved due to packing-protection constraints at the nucleic acid level in addition to protein level constraints. Consequently, nucleic acid secondary structure <it>a priori </it>biases mutations. The converse (exposure of conserved sites) apparently occurs in a smaller number of cases, indicating a different evolutionary adaptive strategy in these plants. The differences between the protection levels of functionally important sites for <it>r</it>- and <it>K-</it>strategists reflect their respective molecular adaptive strategies. These converge with increasing domestication levels of <it>K</it>-strategists, perhaps because domestication increases reproductive output.</p

    Impact of immunogenicity on clinical efficacy and toxicity profile of biologic agents used for treatment of inflammatory arthritis in children compared to adults

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    The treatment of inflammatory arthritis has been revolutionised by the introduction of biologic treatments. Many biologic agents are currently licensed for use in both paediatric and adult patients with inflammatory arthritis and contribute to improved disease outcomes compared with the pre-biologic era. However, immunogenicity to biologic agents, characterised by an immune reaction leading to the production of anti-drug antibodies (ADAs), can negatively impact the therapeutic efficacy of biologic drugs and induce side effects to treatment. This review explores for the first time the impact of immunogenicity against all licensed biologic treatments currently used in inflammatory arthritis across age, and will examine any significant differences between ADA prevalence, titres and timing of development, as well as ADA impact on therapeutic drug levels, clinical efficacy and side effects between paediatric and adult patients. In addition, we will investigate factors associated with differences in immunogenicity across biologic agents used in inflammatory arthritis, and their potential therapeutic implications

    Naval History by Conspiracy Theory: The British Admiralty before the First World War and the Methodology of Revisionism

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    Revisionist interpretations of British naval policy in the Fisher era claim that an elaborate smoke screen was created to hide the Royal Navy’s real policies; while documents showing the true goals were systematically destroyed. By asserting this, revisionists are able to dismiss those parts of the documentary record that contradict their theories, while simultaneously excusing the lack of evidence for their theories by claiming it has been destroyed. This article shows that this methodology is misleading and untenable

    A Refreshing Take: Analysing Accident Scenarios through Causal Network Topology Metrics

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    PresentationAccident causation investigation and even more hazard scenario identification are troubled by the complexity of interactions between three elements in a process facility: People, Plant and Procedures. Interactions are of various nature, such as physical change and information transfer, all influencing the process. To facilitate investigation the digraph network was applied as the most flexible visual aid to describe a causal structure. Such structure consists of nodes and edges representing an event or condition in the accident scenario and a causal link respectively. Attributing the nodes and edges to the type of interaction, numbers of the same type can be counted, and so two metrics are developed: The P3 Interaction Contribution (PIC). This is the proportion of nodes and edges associated with an interaction between People, Plant and Procedures. The Average Edge Weight. This relates to the proportion of events in the scenario that are associated with the logical AND gate conjunction from its causes (incident nodes), where the event requires more than one simultaneous cause. The technique was tried on four CSB accident descriptions. Interesting differences are seen. Also, in view of a paper accepted to be published in Safety Science the approach seems quite helpful in process hazard analysis

    Personalizing neoadjuvant chemotherapy for locally advanced colon cancer:protocols for the international phase III FOxTROT2 and FOxTROT3 randomized controlled trials

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    AIM: FOxTROT1 established a new standard of care for managing locally advanced colon cancer (CC) with neoadjuvant chemotherapy (NAC). Six weeks of neoadjuvant oxaliplatin and fluoropyrimidine (OxFp) chemotherapy was associated with greater 2-year disease-free survival (DFS) when compared with proceeding straight to surgery (STS). There is now a need to refine the use of NAC and identify those most likely to benefit. FOxTROT2 will aim to investigate NAC in older adults and those with frailty. FOxTROT3 will aim to assess whether intensified triplet NAC provides additional benefits over OxFp.METHOD: FOxTROT2 and FOxTROT3 are international, open-label, phase III randomized controlled trials. Eligible patients will be identified by the multidisciplinary team. Patient age, frailty and comorbidities will be considered to guide trial entry. Participants will be randomized 2:1 to the intervention or control arm: 6 weeks of dose-adapted neoadjuvant OxFp versus STS in FOxTROT2 and 6 weeks of neoadjuvant modified oxaliplatin, 5-fluorouracil and irinotecan versus OxFp in FOxTROT3. The primary endpoint in FOxTROT2 is 3-year DFS. In FOxTROT3, tumour regression grade and 3-year DFS are co-primary endpoints.DISCUSSION: FOxTROT2 and FOxTROT3 will establish the FOxTROT platform, a key part of our long-term strategy to develop neoadjuvant treatments for CC. FOxTROT2 will investigate NAC in a population under-represented in FOxTROT1 and wider research. FOxTROT3 will assess whether it is possible to induce greater early tumour responses and whether this translates to superior long-term outcomes. Looking ahead, the FOxTROT platform will facilitate further trial comparisons and extensive translational research to optimize the use of NAC in CC.</p
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