CDK9 and mTOR: trading places.
Ontology highlight
ABSTRACT:
SUBMITTER: Borden KLB
PROVIDER: S-EPMC6418479 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
Publications
Similar Datasets
Project description:BackgroundPerson trade-off (PTO) elicitations yield different values than standard utility measures, such as time trade-off (TTO) elicitations. Some people believe this difference arises because the PTO captures the importance of distributive principles other than maximizing treatment benefits. We conducted a qualitative study to determine whether people mention considerations related to distributive principles other than QALY-maximization more often in PTO elicitations than in TTO elicitations and whether this could account for the empirical differences.Methods64 members of the general public were randomized to one of three different face-to-face interviews, thinking aloud as they responded to TTO and PTO elicitations. Participants responded to a TTO followed by a PTO elicitation within contexts that compared either: 1) two life-saving treatments; 2) two cure treatments; or 3) a life-saving treatment versus a cure treatment.ResultsWhen people were asked to choose between life-saving treatments, non-maximizing principles were more common with the PTO than the TTO task. Only 5% of participants considered non-maximizing principles as they responded to the TTO elicitation compared to 68% of participants who did so when responding to the PTO elicitation. Non-maximizing principles that emerged included importance of equality of life and a desire to avoid discrimination. However, these principles were less common in the other two contexts. Regardless of context, though, participants were significantly more likely to respond from a societal perspective with the PTO compared to the TTO elicitation.ConclusionWhen lives are at stake, within the context of a PTO elicitation, people are more likely to consider non-maximizing principles, including the importance of equal access to a life-saving treatment, avoiding prejudice or discrimination, and in rare cases giving treatment priority based purely on the position of being worse-off.
| S-EPMC1310516 | biostudies-literature
Project description:This paper describes a dataset capturing insider trading activity at publicly traded companies. Investors and investment analysts demand this information because executives, directors and large shareholders are expected to have more intimate knowledge of their company's prospects than outsiders. Insider stock sales and purchases may reveal information about the firm's business not disclosed in financial statements. They may also convey new information predictive of stock price movements if insiders can better interpret public information about the firm. Since mid-2003, the Securities and Exchange Commission has made these insider trading reports available to the public in a structured format; however, most academic papers use proprietary commercial databases instead of regulatory filings directly. This makes replication challenging as the data manipulation and aggregation processes are opaque and historical records could be altered by the database provider over time. To overcome these limitations, the presented dataset is created from original regulatory filings; it is updated daily and includes all information reported by insiders without alteration.
| S-EPMC10130014 | biostudies-literature
Project description:Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a promising target for cancer therapy, particularly for cancers driven by transcriptional dysregulation. We characterized NVP-2, a selective ATP-competitive CDK9 inhibitor, and THAL-SNS-032, a selective CDK9 degrader consisting of a CDK-binding SNS-032 ligand linked to a thalidomide derivative that binds the E3 ubiquitin ligase Cereblon (CRBN). To our surprise, THAL-SNS-032 induced rapid degradation of CDK9 without affecting the levels of other SNS-032 targets. Moreover, the transcriptional changes elicited by THAL-SNS-032 were more like those caused by NVP-2 than those induced by SNS-032. Notably, compound washout did not significantly reduce levels of THAL-SNS-032-induced apoptosis, suggesting that CDK9 degradation had prolonged cytotoxic effects compared with CDK9 inhibition. Thus, our findings suggest that thalidomide conjugation represents a promising strategy for converting multi-targeted inhibitors into selective degraders and reveal that kinase degradation can induce distinct pharmacological effects compared with inhibition.
| S-EPMC5912898 | biostudies-literature
Project description:COVID-19 raises attention to epidemic transmission in various places. This study analyzes the transmission risks associated with human activity places at multiple scales, including different types of settlements and eleven types of specific establishments (restaurants, bars, etc.), using COVID-19 data in 906 urban areas across four continents. Through a difference-in-difference approach, we identify the causal effects of activities at various places on epidemic transmission. We find that at the micro-scale, though the transmission risks at different establishments differ across countries, sports, entertainment, and catering establishments are generally more infectious. At the macro-scale, contradicting common beliefs, it is consistent across countries that transmission does not increase with settlement size and density. It is also consistent that specific establishments play a lesser role in transmission in larger settlements, suggesting more transmission happening elsewhere. These findings contribute to building a system of knowledge on the linkage between places, human activities, and disease transmission.
| S-EPMC9630073 | biostudies-literature
Project description:To accommodate China's electricity market reforms integrating medium and long-term (MLT) transactions and spot transactions, and to boost renewable energy consumption through the spot market, this paper proposes an optimized cross-provincial electricity trading strategy model based on a two-layer game framework. The proposed model incorporates an MLT green certificate contract decomposition method, enabling nested optimization of green certificate contracts and scheduling plans for cross-provincial power transactions. To encourage broader participation, a bilateral green certificate trading framework is established, which globally optimizes green certificate allocation to increase benefits for market participants. A Nash-Stackelberg game model is introduced to address complex game interactions among multiple participants under the green certificate mechanism and the limitation of assuming complete rationality. The game model combines supply and demand sides with an embedded demand-side evolutionary game. Additionally, an improved Aquila optimization algorithm (IAOA) is developed to accurately calculate electricity supply and demand. The algorithm integrates a Circle chaotic map, Sobol sequence, random walk strategy, and filtering technology to enhance optimization capabilities and manage complex constraints. The algorithm is then embedded with a distributed iterative approach to achieve equilibrium strategies. A real-world case study was conducted to validate the feasibility and effectiveness of the proposed model. The results demonstrate that the proposed approach effectively achieves equilibrium, optimizes trading strategies, and fosters win-win, coordinated development among participants in the cross-provincial electricity market.
| S-EPMC11614898 | biostudies-literature
Project description:ObjectivesMost people, including Indigenous people in Ontario, wish to die in their communities. How often Indigenous people in Ontario die in their preferred settings is unknown. This study aims to describe the places of care and death for Indigenous people in Ontario who received provincially funded home care services.MethodsWe conducted a retrospective cohort study using linked health administrative databases housed at ICES. We used a population-based cohort of Indigenous and non-Indigenous people in Ontario who died between April 1, 2010 and March 31, 2015 to describe characteristics of people, places of death, and places of care.ResultsIndigenous decedents were on average 8.8 years younger, had more chronic diseases, and lived in lower income neighbourhoods compared with their non-Indigenous counterparts. Indigenous decedents spent nearly 8 more days in acute care in the last year of life and more died in acute care (56.1% versus 46.1%). When controlling for covariates, Indigenous decedents received 1.9 fewer home care nursing hours and 5 fewer personal support worker hours and showed decreased odds (OR 0.72) of receiving a palliative physician visit in the last 90 days of life. Among Indigenous decedents, a palliative physician visit lowered odds of dying in acute care by 50% and total days in acute care by 18%.ConclusionOur study identified a gap in end-of-life care for Indigenous Peoples in Ontario receiving provincially funded home care. Without continued efforts to address challenges that perpetuate health inequalities, we expect many Indigenous people will continue to die in acute care away from their people, families, and culturally relevant supports.
| S-EPMC8225727 | biostudies-literature
Project description:The day trading in Taiwanese stock market expands considerably at the beginning of 2016, which increases the transactions of stocks consequently and sparks our interest in exploring the issue of day trading. In this study, we use the data of Taiwan Stock Exchange listed firms to investigate whether the day trading volume over total trading volume (hereinafter referred to as the day trading ratio) and the turnover ratio enhanced by the increase of day trading volume would affect the shareholding and trading behaviors of diverse institutional and individual investors. Unquestionably, we bring out several impressive findings. First, foreign institutional investors would not prefer holding or trading the stocks with high day trading ratios, whereas individual investors would prefer holding these kinds of stocks. We infer that this finding might result from the fundamental and the speculative concerns of these various investors. Second, domestic institutional investors and security dealers would prefer trading the stocks with high turnover ratios, but foreign institutional investors still lack of interest in trading these stocks, implying that the investment strategies would be dissimilar among various institutional investors. Since foreign institutional investors are regarded as the successful institutional investors in Taiwan, we argue that our revealed results may help market participants trace the behaviors of diverse investors, especially the foreign institutional investors, after day trading relaxation in Taiwan.
| S-EPMC8064584 | biostudies-literature
Project description:Cyclin dependent kinase 9 (CDK9) plays an essential role in regulating transcriptional elongation. Aberrations in CDK9 activity have been observed in various cancers, which make CDK9 an attractive therapeutic target for cancers. This led to an intensive development of small-molecule CDK9 inhibitors or new emerging strategies, such as proteolysis targeting chimeras (PROTACs). Here, we review the CDK9 modulators in cancer not only for research purposes, but also for therapeutic applications.
| S-EPMC9215160 | biostudies-literature
Project description:We examine individual-level trading data from several markets in the PredictIt exchange to determine what strategies correlate with financial success. PredictIt provides many markets with futures contracts linked to political issues, ranging from ongoing policy outcomes to political elections. High fees along with restrictions blocking automatic trading and constraining a one-to-one match between people and accounts, combine to severely limit the upside to investment returns over the fixed costs: this ensures that traders are all retail investors. We have the individual-level data from two markets: Democratic and Republican Iowa Caucuses in 2016. This data includes all orders and trades from every trader across the markets. We are able to fully reconstruct market activity and study trader behavior both within and between markets. We show that understanding how markets and trades works is more important to financial success than proxies for (1) confidence or funding (2) information or objectivity in trading. The work should be a call-to-action in favor of simplifying markets and trading for any exchange with retail investors, and for more research into effects of differential trading efficiency in all financial markets.
| S-EPMC6703684 | biostudies-literature
Project description:Brazil faces an enormous challenge to implement its revised Forest Code. Despite big losses for the environment, the law introduces new mechanisms to facilitate compliance and foster payment for ecosystem services (PES). The most promising of these is a market for trading forest certificates (CRAs) that allows landowners to offset their restoration obligations by paying for maintaining native vegetation elsewhere. We analyzed the economic potential for the emerging CRA market in Brazil and its implications for PES programs. Results indicate a potential market for trading 4.2 Mha of CRAs with a gross value of US$ 9.2±2.4 billion, with main regional markets forming in the states of Mato Grosso and São Paulo. This would be the largest market for trading forests in the world. Overall, the potential supply of CRAs in Brazilian states exceeds demand, creating an opportunity for additional PES programs to use the CRA market. This expanded market could provide not only monetary incentives to conserve native vegetation, but also environmental co-benefits by fostering PES programs focused on biodiversity, water conservation, and climate regulation. Effective implementation of the Forest Code will be vital to the success of this market and this hurdle brings uncertainty into the market. Long-term commitment, both within Brazil and abroad, will be essential to overcome the many challenges ahead.
| S-EPMC4822866 | biostudies-literature