185 research outputs found
Post-modern cowboys: The transformation of sport in the twentieth century
During the twentieth century, sports that evolved in the American West transformed the landscape of American sport. Driven by combinations of technology, media, and human personalities, sports such as surfing, skateboarding, and mountain biking redefined the meaning of sport and eliminated the traditional limits to the playing field. As surfing, skateboarding, and mountain biking evolved, wartime technologies accelerated their progress. Those technologies democratized access to contemporary sports in two ways. Materials such as polyurethane eased the physical requirements of carrying equipment and catching waves. Contemporary sports also expanded access because they focused on individualized competition and participation, eliminating the need for other players as a prerequisite to participation. As contemporary sports evolved in the West, they gradually eclipsed the participatory dominance of traditional team sports
The Economics of Nested Insurance: The Case of SURE
Traditionally, disaster assistance was available on an ad hoc basis, but the 2008 Farm Act provides a standing disaster assistance program known as Supplemental Revenue Assistance (SURE). This paper introduces a theory of nested insurance to evaluate the impact on of SURE on intensification, acreage and adoption. The results suggest that parameters of a government program like SURE may enhance the adoption and value of crop insurance to the farm sector. A quantitative understanding of the interdependencies between programs like SURE and crop insurance, taking into account the nature of the ad hoc alternative, is important in assessing the welfare impacts on farmers, as well as insurance companies. Both our theory and simulation exercise suggest that insurance increases the volume of production and/or leads to increased intensification (substitution into higher value crops). On the other hand, the gains from insurance and from programs like SURE may be lessened by the presence and probability of ad hoc disaster assistance.Nested insurance, SURE, crops, adoption, ad hoc, disaster assistance, Crop Production/Industries, Risk and Uncertainty,
Environmental Policy with Collective Waste Disposal
Centralized collection and disposal is an integral component of waste management strategies for many solid and liquid wastes, and carbon capture and storage is currently being considered for gaseous waste. In this paper we show how collective waste disposal systems introduce essential changes in the design of optimal environmental policy. Absent collective disposal, an optimal environmental policy imposes relatively stringent regulations on polluters in regions where local environmental damage functions are “high”; however, under collective waste disposal, the optimal environmental policy level increases monotonically over distance from the disposal site, and this is true irrespective of the degree of spatial heterogeneity in local environmental damage functions. We characterize the optimal spatial pattern of environmental policy levels under collective waste disposal and identify optimal membership size for waste disposal networks comprised of homogeneous producers
Deductibles vs. Coinsurance in Shallow-Loss Crop Insurance
Shallow-loss policies take center-stage in many proposals for the current Farm Bill. We examine the choice of deductible coverage vs. coinsurance to show risk premiums and loss adjustment costs matter little when comparing policies. Thus, policy makers should base decisions more on costs to taxpayers than specific risk management features
Targeting of Rac GTPases blocks the spread of intact human breast cancer
High expression of Rac small GTPases in invasive breast ductal carcinoma is associated with poor prognosis, but its therapeutic value in human cancers is not clear. The aim of the current study was to determine the response of human primary breast cancers to Rac-based drug treatments ex vivo. Three-dimensional organotypic cultures were used to assess candidate therapeutic avenues in invasive breast cancers. Uniquely, in these primary cultures, the tumour is not disaggregated, with both epithelial and mesenchymal components maintained within a three-dimensional matrix of type I collagen. EHT 1864, a small molecule inhibitor of Rac GTPases, prevents spread of breast cancers in this setting, and also reduces proliferation at the invading edge. Rac1+ epithelial cells in breast tumours also contain high levels of the phosphorylated form of the transcription factor STAT3. The small molecule Stattic inhibits activation of STAT3 and induces effects similar to those seen with EHT 1864. Pan-Rac inhibition of proliferation precedes down-regulation of STAT3 activity, defining it as the last step in Rac activation during human breast cancer invasion. Our data highlights the potential use of Rac and STAT3 inhibition in treatment of invasive human breast cancer and the benefit of studying novel cancer treatments using three-dimensional primary tumour tissue explant cultures
Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation.
Epigenetic reprogramming is a cancer hallmark, but how it unfolds during early neoplastic events and its role in carcinogenesis and cancer progression is not fully understood. Here we show that resetting from primed to naïve human pluripotency results in acquisition of a DNA methylation landscape mirroring the cancer DNA methylome, with gradual hypermethylation of bivalent developmental genes. We identify a dichotomy between bivalent genes that do and do not become hypermethylated, which is also mirrored in cancer. We find that loss of H3K4me3 at bivalent regions is associated with gain of methylation. Additionally, we observe that promoter CpG island hypermethylation is not restricted solely to emerging naïve cells, suggesting that it is a feature of a heterogeneous intermediate population during resetting. These results indicate that transition to naïve pluripotency and oncogenic transformation share common epigenetic trajectories, which implicates reprogramming and the pluripotency network as a central hub in cancer formation
Відгук офіційного опонента доктора філологічних наук, професора Кузьменка В.І. на дисертацію Галича А.О. за темою Жанрові модифікації портретного дискурсу в документалістиці ХХ – ХХІ ст
У дисертації вперше в українському літературознавстві здійснено комплексне дослідження особливостей портретування в документальній літературі, осмислено його специфіку у творах різних жанрів, простежено складники портретних характеристик, визначено домінантні підходи до створення портретів. Удосконалено системну класифікацію портретів в українській документалістиці згідно з новітніми досягненнями літературознавства. Уточнено структуру, семіотику й семантику портрета в різних жанрах мемуарної, біографічної (автобіографічної) літератури. Набули подальшого розвитку модифікації портретів у документальних творах. Розширено й уточнено формулювання низки теоретичних понять, зокрема таких, як портрет, концентрований портрет, деконцентрований портрет, автопортрет, парний портрет, колективний портрет, оніричний портрет, некропортрет. Залучено до аналізу тексти, зокрема останніх літ, які досі не були предметом наукових студій, а також маловідомі архівні матеріали.У дисертації вперше в українському літературознавстві здійснено комплексне дослідження особливостей портретування в документальній літературі, осмислено його специфіку у творах різних жанрів, простежено складники портретних характеристик, визначено домінантні підходи до створення портретів. Удосконалено системну класифікацію портретів в українській документалістиці згідно з новітніми досягненнями літературознавства. Уточнено структуру, семіотику й семантику портрета в різних жанрах мемуарної, біографічної (автобіографічної) літератури. Набули подальшого розвитку модифікації портретів у документальних творах. Розширено й уточнено формулювання низки теоретичних понять, зокрема таких, як портрет, концентрований портрет, деконцентрований портрет, автопортрет, парний портрет, колективний портрет, оніричний портрет, некропортрет. Залучено до аналізу тексти, зокрема останніх літ, які досі не були предметом наукових студій, а також маловідомі архівні матеріали.У дисертації вперше в українському літературознавстві здійснено комплексне дослідження особливостей портретування в документальній літературі, осмислено його специфіку у творах різних жанрів, простежено складники портретних характеристик, визначено домінантні підходи до створення портретів. Удосконалено системну класифікацію портретів в українській документалістиці згідно з новітніми досягненнями літературознавства. Уточнено структуру, семіотику й семантику портрета в різних жанрах мемуарної, біографічної (автобіографічної) літератури. Набули подальшого розвитку модифікації портретів у документальних творах. Розширено й уточнено формулювання низки теоретичних понять, зокрема таких, як портрет, концентрований портрет, деконцентрований портрет, автопортрет, парний портрет, колективний портрет, оніричний портрет, некропортрет. Залучено до аналізу тексти, зокрема останніх літ, які досі не були предметом наукових студій, а також маловідомі архівні матеріали
Tissue of origin determines cancer-associated CpG island promoter hypermethylation patterns
ABSTRACT: BACKGROUND: Aberrant CpG island promoter DNA hypermethylation is frequently observed in cancer and is believed to contribute to tumor progression by silencing the expression of tumor suppressor genes. Previously, we observed that promoter hypermethylation in breast cancer reflects cell lineage rather than tumor progression and occurs at genes that are already repressed in a lineage-specific manner. To investigate the generality of our observation we analyzed the methylation profiles of 1,154 cancers from 7 different tissue types. RESULTS: We find that 1,009 genes are prone to hypermethylation in these 7 types of cancer. Nearly half of these genes varied in their susceptibility to hypermethylation between different cancer types. We show that the expression status of hypermethylation prone genes in the originator tissue determines their propensity to become hypermethylated in cancer; specifically, genes that are normally repressed in a tissue are prone to hypermethylation in cancers derived from that tissue. We also show that the promoter regions of hypermethylation-prone genes are depleted of repetitive elements and that DNA sequence around the same promoters is evolutionarily conserved. We propose that these two characteristics reflect tissue-specific gene promoter architecture regulating the expression of these hypermethylation prone genes in normal tissues. CONCLUSIONS: As aberrantly hypermethylated genes are already repressed in pre-cancerous tissue, we suggest that their hypermethylation does not directly contribute to cancer development via silencing. Instead aberrant hypermethylation reflects developmental history and the perturbation of epigenetic mechanisms maintaining these repressed promoters in a hypomethylated state in normal cells.Publisher PDFPeer reviewe
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