This paper presents an analytical framework to assess the probability of achieving nationally determined contributions (NDC). The prediction model based on the Kaya identity is used to simulate the pathway of carbon emission until the target year. Applying the modified STIRPAT framework (named CO-STIRPAT) to data observed in South Korea shows that the probability that the predicted pathway with existing climate technology will stay above the NDC target pathway is significantly high. The result suggests that it is necessary to design a climate policy to improve energy intensity and carbon intensity by accelerating the advance in climate technology.

This paper presents an operational framework for assessing the trajectories of production, energy, emissions, and capital accumulation to ensure the implementation of Nationally Determined Contributions (NDCs). The framework combines widely used methodologies (STIRPAT, system dynamics, and optimization) to simulate the pathways of variables until a target year. The CO-STIRPAT dynamic system allows us to identify the spillover pathways from carbon policy to economic growth based on output optimization principles; to conduct a more systematic analysis of the interconnections between the main drivers that determine carbon emissions; to develop a cost-effective climate policy mix that is a backbone for the right combination of carbon pricing, energy efficiency, and carbon intensity; and to assess NDC targets with respect to ambition gaps, implementation gaps, and feasibility.

In his 1922 review for Cambridge Magazine of Keynes's A Treatise on Probability, and again in his 1926 review "Truth and Probability" (published in 1931 and republished in Kyburg and Smokler's 1980 edition), Ramsey provided examples critiquing Keynes's logical theory of probability. However, these examples do not disprove Keynes's theory as all of them are flawed. The flaws arise because all the pairs of propositions that Ramsey used to substantiate his criticisms are irrelevant to each other. Such irrelevant propositions are explicitly excluded from Keynes's theory in pages 4-6 of his A Treatise on Probability. This paper highlights that Ramsey's examples, which involve irrelevant propositions, do not disprove Keynes's Boolean, relational logic. The only other defense of Keynes's theory, put forth by Watt in 1989, was found to be deficient by Brady in 2022.

Breast cancer, as a malignant tumor with easy metastasis and poor prognosis, threatens the health of women around the world. Increasing studies have shown that the Bcl-2 family of apoptosis-related proteins is often expressed abnormally in breast cancer. The Bcl-2 homology 3 (BH3) mimetic peptide can bind and neutralize Bcl-2, preventing its binding to the apoptosis "effector" proteins Bak and Bax, thereby promoting the apoptosis process. However, there is a lack of effective intracellular delivery system for BH3 to exert its biological activity. Therefore, this study utilized an activatable supercharged polypeptide (ASCP) tumor-targeted delivery platform based on pH and protease response to achieve the targeted release of BH3 at the tumor site. Ultimately, intracellular delivery of BH3 was achieved and induced apoptosis of breast tumor cells, preventing the development of breast cancer.

Cancer treatment faces multiple challenges, including tumor heterogeneity, drug resistance, microenvironment influence, treatment side effects, and treatment cost. The heterogeneity of the tumor makes the effect of the same treatment vary in different patients, so the development of personalized treatment strategies is crucial. In addition, resistance of tumor cells to therapeutic drugs is a major challenge, and new strategies to overcome resistance are needed. As a cutting-edge field of science and technology, nanotechnology has brought great potential and opportunities for tumor treatment. Nanoparticle drug delivery systems improve drug efficacy and reduce side effects through precise targeted delivery and controlled release. Cell-membrane coated nanoparticles show great promise in tumor therapy. Nanoparticles coated with cell membranes have good biocompatibility, can reduce the obstacles of immune rejection and cell uptake, improve the accumulation and retention of drugs in tumor tissues, and have good drug delivery ability, drug stability and control release ability. This review discusses advances in the use of cell-membrane coated nanoparticles to target tumor drugs.

Major economic and financial contractions usually go hand-in-hand with muted inflation. This has been true for the Great Depression, the Global Financial Crisis, as well as the Covid-19 crisis. In this paper, we theoretically highlight and discuss the evolution of instruments and approaches monetary-policy decision makers at the Federal Reserve have in lifting inflation to desired levels in times of the zero-lower bound, paying particular focus on more rigorous developments like asymmetric average inflation and temporary price-level targeting.

Metadherin (MTDH), also known as LYRIC or AEG-1, is an oncogene that enhances tumor progression, metastasis, drug resistance, and immune escape in various cancers by modulating multiple oncogenic pathways, including NF-κB, PI3K/AKT, Wnt/β-catenin, MAPK, and AMPK. Due to the unknown of the complete structure of MTDH, the deep mechanisms of MTDH and selective inhibitors targeting MTDH remain to be explored. The Protein-Protein interaction (PPI) with the Staphylococcal nuclease domain containing 1 (SND1) is a crucial mechanism underlying the function of MTDH. Current studies have demonstrated that inhibitors, including antisense oligonucleotides, peptides, and small molecules targeting MTDH or MTDH-SND1 interactions, provide novel strategies to inhibit the oncogenetic effects of MTDH. This review summarizes and discusses the structure, function, and regulation of MTDH in cancers, providing the potential therapeutic perspectives of MTDH or MTDH-SND1 PPI for drug discovery.

Nanomaterials have shown great potential in anti-tumor applications and are currently the focus of research. This review article aims to provide a comprehensive overview of the challenges encountered in oncology treatment and how nanomaterials are being utilized to overcome these obstacles. The authors discuss the limitations of conventional treatments, including limited efficacy, side effects, and toxicity issues. They highlight the importance of early tumour diagnosis and personalized treatment plans, as well as the need for innovative therapeutic approaches such as targeted therapy, immunotherapy, and gene therapy. The article primarily focuses on how nanomaterials can be engineered to achieve specific recognition and aggregation within tumour tissues through surface modifications involving targeting molecules such as antibodies, peptides, and receptor ligands. This surface modification technique facilitates improved targeting in the targeting of photodynamic therapy, while minimizing harm to normal tissues. The authors also discuss the potential and future prospects of nanomaterials in tumour therapy, including breakthroughs in their application, biosafety concerns, biocompatibility issues, preparation processes, clinical translation challenges, interdisciplinary cooperation, international exchange, relevant regulations and ethical guidelines. Overall, this review highlights the substantial potential of nanomaterials in oncology treatment, emphasizing the need for careful consideration of safety concerns to ensure their safe and effective application. The authors conclude that strengthening interdisciplinary cooperation and international exchange will contribute to the healthy development of nanomaterials in oncology treatment.

Approximately 28 million individuals in the United States face the risk of developing precancerous colonic adenomas (polyps) and potentially progressing to colorectal cancer (CRC). While a promising strategy for CRC prevention involves pharmacological intervention, such as cancer chemoprevention or interception, currently, there are no FDA-approved drugs capable of preventing the formation or progression of adenomas to adenocarcinoma. Numerous clinical, epidemiological, and preclinical studies have offered compelling evidence supporting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in CRC chemoprevention. However, the prolonged use of NSAIDs is not FDA-approved due to potential life-threatening toxicities resulting from cyclooxygenase (COX) inhibition and the depletion of physiological prostaglandins. Despite indications that the COX inhibitory activity of NSAIDs may not be essential for their antineoplastic effects, the absence of a well-defined target impeded the development of derivatives that do not inhibit COX. Earlier research suggests that the inhibition of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) may be responsible, at least in part, for the antineoplastic activity of the NSAID sulindac. This could potentially offer a novel target for CRC chemoprevention. To identify the cGMP PDE isozyme(s) contributing to the antineoplastic activity of sulindac, we synthesized a chemically diverse library of over 1500 compounds, all sharing the indene scaffold of sulindac. Subsequently, we screened these compounds for their impact on cancer cell growth and PDE inhibitory activity. From this screening, a series of lead compounds emerged. These compounds lacked COX-1 and COX-2 inhibitory activity, surpassing sulindac in potency to inhibit CRC cell growth. Importantly, they demonstrated greater selectivity by not affecting normal cell growth. Through chemical optimization, we identified several development candidates that selectively inhibit PDE5 and/or PDE10. These compounds activate cGMP/PKG signaling, suppressing Wnt/β-catenin transcription. This action counters the growth advantages resulting from APC or CTNNB1 mutations, which are responsible for most human CRCs. This review delves into the scientific literature supporting PDE5 and/or PDE10 as potential targets for CRC chemoprevention or interception. Our findings suggest a promising avenue for developing drugs that may effectively intervene in the progression of colorectal cancer, offering hope for improved preventive strategies in the future.

Cancer, a pervasive threat to human health, presents formidable challenges to traditional treatment approaches. Tumor immunotherapy has emerged as a promising strategy for combating malignancies by bolstering the body's immune response to thwart tumor metastasis and recurrence. Nonetheless, the intricacies of tumors, patient heterogeneity, and the presence of tumor-immunosuppressive microenvironments have limited the overall efficacy of immunotherapy, achieving only approximately a 20% success rate. In recent years, nanomaterials have garnered increasing attention in the realm of tumor immunotherapy due to their inherent advantages, such as excellent biocompatibility, precise targeting, and controlled drug release. Nanomaterials empower immunostimulatory molecules and therapeutic agents with the ability to specifically target tumors, amplify drug accumulation at tumor sites, facilitate local immune modulation, alleviate immunosuppressive microenvironments, and thereby enhance the effectiveness of tumor immunotherapy. This review provides an overview of the current state of immunotherapy and offers insights into the ongoing research progress surrounding various nanomaterials aimed at augmenting the efficacy of immunotherapy.

Since the Industrial Revolution, the emission of carbon dioxide and other greenhouse gases by human production activities has increased year by year, and the greenhouse effect has also increased. A series of problems, such as global warming, melting of the Antarctic continent, sea level rise and frequent occurrence of extreme climate, have attracted the attention of countries all over the world. As a developing country with the fastest economic growth rate, China's rapid economic growth is inseparable from the contribution of manufacturing industry. As an important engine of China's economic development, manufacturing industry inevitably brings environmental problems and a large number of greenhouse gas emissions while promoting rapid economic development. Therefore, manufacturing has become a major area for China to achieve its carbon emission reduction targets. With the "Made in China" to the world, the export trade of manufacturing industry plays a decisive role in China's total export trade and even the global trade. But whether the huge export demands will affect carbon emissions. Through the empirical study on carbon emissions of China's manufacturing export trade, the paper found that the increase of export demand of manufacturing industry will indeed bring a significant increase in carbon emissions, but also affected by some other factors. Finally, it provides reference for the high-quality development and export of China's manufacturing industry under the background of the target of “dual-carbon”.

Alternative bio actively chemicals may be found in natural goods and traditional herb medications, but only a few plant-information formulations have been rigorously studied and verified for their potential as medicinal therapies. The study of plant-derived elements' immunomodulation capabilities and their ability as provoke the immune system as combat various elemental disorders like cancer is, nonetheless, a promising area in current therapeutics information on plant-derived chemicals. This research showed how network pharmacology may be applied as define and validate natural individual elements or more complicated preparations as prospective cancer therapies information on their various aim capabilities in this research. We give a summary of the present state of understanding on network pharmacology, with a particular emphasis on various technical methods and their implications for cancer treatment.

Liquidity and its associated issues are one of dominant strands in the market microstructure. In this study, microblogging-based behavioral perspective on economic unrest is linked to the market liquidity. The concept of liquidity is examined in terms of price dispersion relative to the quantity traded. The analysis contains the quantification of multiple linear regression, Gaussian distribution technique, and vector error correction methodology. In the economic stability period, the investor’s mood, either in positive manner or pessimistic context, had an influential role on the price impact volume-based liquidity. Meantime, the probability was higher for occurrence of price impact volume-based liquidity in response to the sentiment indicators. In the economic unrest environments, the positive bias investor’s mood was not vigorous enough to influence the dispersion of asset’s prices and trading quantity. Most importantly, the negative bias investor’s emotion was linked to increase the dispersion of asset’s prices relative to the quantity traded. Investors with a lower amount of trading quantity had declined the liquidity in the market. Additionally, there was a higher probability for occurrence of illiquidity in the pessimistic market periods. However, changes in past sentiment series were not associated with changes in pervious liquidity series, either in short run or long run. The findings may be potentially applicable to manage the behavioral perspective of liquidity risk.

The stages of liver fibrosis can reflect the severity of chronic viral hepatitis and the probability of liver cancer. Biopsy is still regarded as the reference for staging fibrosis, but the invasive method is not suitable for first-line screening. In recent years, noninvasive methods for detecting virus-driven liver fibrosis have been developed rapidly, which mainly include biological (serum biomarkers indexes) and physical (imaging assessment of liver stiffness) strategies. In this review, we introduce these noninvasive methods, enumerate their diagnosis performances and discuss the role of ferroptosis. At last, we propose directions for future researches.

Calculating the amount of regulatory capital to cover unexpected losses due to operational events in the upcoming year has caused problems because of difficulties in fitting probability distributions to data. It is consequently difficult to judge an appropriate level of capital that reflects the risk profile of a financial institution. We provide theoretical and empirical analyses to link the calculated capital to the sum of losses using appropriate statistical approximations. We conclude that, in order to reasonably reflect the associated risk, the capital should be approximately half the sum of losses, with a wide bound for the ratio of capital to sum.

This paper empirically investigates the relation between firm performance in corporate social responsibility (CSR) and the need and likelihood of external financing to test the predictions of agency and stakeholder theories. Empirical results from Logit, Linear Probability Model, OLS and Firm fixed effects regressions indicate that CSR is negatively related to the likelihood and level of external financing. Further analysis indicates that CSR has a negative and significant effect on both net equity issued (NEI) and net debt issued (NDI), the two components of external financing. Overall, the empirical results support the predictions of agency theory.

This study aims to examine the effects of student loan debt on the decisions of U.S. married households to invest in stocks located in non-retirement accounts. Using longitudinal datasets from the 2011 to 2017 U.S. Panel Study of Income Dynamics and a fixed effects logit model, the results show mixed findings. The presence of student debt decreases the probability that married households will own stocks, but the amount of student debt does not show a statistically significant effect. The findings suggest that the incidence of student debt raises the perception of liquidity constraints and debt burden among married households.

Consideration of optimal commodity storage with different discount rates. Finding that, even with a lower discount rate than private storage, optimal government-financed storage may not narrow price fluctuations compared with optimal privately financed storage because a government has to choose a probability of buffer stock failure greater than zero to economize on storage costs that could conceivably become very large. There is no presumption that government financed storage would be larger, with narrower intervention bands and more stable prices, than with privately-financed storage. The welfare enhancing effect of government financed storage compared to private storage is therefore indeterminate.

This study analyses the effects of piped water on household food consumption per capita by adopting inverse-probability-weighted regression adjustment and endogenous treatment effects approaches with data from the Cambodia Socio-Economic Survey carried out in 2013 and 2017. A complementary analysis of the effects on primary household income per working-age member is also conducted to give insights into the potential consequences. The study also conducts a robustness check by estimating the fixed effects of piped water utilising village panel data. The results suggest that households using piped water are likely to enjoy higher food consumption per capita, with a complementary finding demonstrating that the use of piped water is likely to increase household income per working-age member.

We quantify financial returns to backers in reward-based crowdfunding projects on Kickstarter and show that such investments provide profitable opportunities in addition to non-monetary benefits. The average unconditional annualized return is 11.5% and the average return on successful projects is 30%. Hence, backing money near the end of a campaign, when the probability of success is already high, is a profitable strategy. The most attractive is the Design category, where successful projects yield 73%, on average. Short-term projects are more profitable than long-term ones. Financial return is an important type of extrinsic motivation in reward-based crowdfunding, which has generally been neglected in academic literature. Reward-based crowdfunding outperforms other forms of crowdfunding and other common alternative investments.