This paper studies a joint pricing and product quality decision problem in a distribution channel, in which a manufacturer sells a product through a retailer. The manufacturer jointly determines the ...wholesale price and quality of the product, and the retailer determines the retail price. We find that if the marginal revenue function is strictly concave, then the manufacturer chooses a lower product quality level than if selling the product directly to customers. If the marginal revenue function is affine, then the manufacturer's optimal product quality decision is independent of the distribution channel structure. If the marginal revenue function is strictly convex, then the manufacturer chooses a higher product quality level than if selling the product directly to customers.
COVID‐19 and Inequalities Blundell, Richard; Costa Dias, Monica; Joyce, Robert ...
Fiscal studies,
June 2020, 2020-06-00, 20200601, Letnik:
41, Številka:
2
Journal Article
Recenzirano
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This paper brings together evidence from various data sources and the most recent studies to describe what we know so far about the impacts of the COVID‐19 crisis on inequalities across several key ...domains of life, including employment and ability to earn, family life and health. We show how these new fissures interact with existing inequalities along various key dimensions, including socio‐economic status, education, age, gender, ethnicity and geography. We find that the deep underlying inequalities and policy challenges that we already had are crucial in understanding the complex impacts of the pandemic itself and our response to it, and that the crisis does in itself have the potential to exacerbate some of these pre‐existing inequalities fairly directly. Moreover, it seems likely that the current crisis will leave legacies that will impact inequalities in the long term. These possibilities are not all disequalising, but many are.
Reductive mobilization of arsenic (As) in paddy soils under flooded conditions is an important reason for the relatively high accumulation of As in rice, posing a risk to food safety and human ...health. The extent of As mobilization varies widely among paddy soils, but the reasons are not well understood. In this study, we investigated As mobilization in six As-contaminated paddy soils (total As ranging from 73 to 122 mg kg−1) in flooded incubation and pot experiments. Arsenic speciation in the solution and solid phases were determined. The magnitude of As mobilization into the porewater varied by > 100 times among the six soils. Porewater As concentration correlated closely with the concentration of oxalate-extractable As, suggesting that As associated with amorphous iron (oxyhydr)oxides represents the potentially mobilizable pool of As under flooded conditions. Soil containing a high level of manganese oxides showed the lowest As mobilization, likely because Mn oxides retard As mobilization by slowing down the drop of redox potential upon soil flooding and maintaining a higher arsenate to arsenite ratio in the solid and solution phases. Additions of a synthetic Mn oxide (hausmannite) to two paddy soils increased arsenite oxidation, decreased As mobilization into the porewater and decreased As concentrations in rice grain and straw. Consistent with previous studies using simplified model systems or pure mineral phases, the present study shows that Mn oxides and amorphous Fe (oxyhydr)oxides are important factors controlling reductive As mobilization in As-contaminated paddy soils. In addition, this study also suggests a potential mitigation strategy using exogenous Mn oxides to decrease As uptake by rice in paddy soils containing low levels of indigenous Mn oxides, although further work is needed to verify its efficacy and possible secondary effects under field conditions.
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•Reductive arsenic mobilization differed by > 100 times among six paddy soils with similar total As.•Oxalate-extractable As was a good indicator of potentially mobilizable As.•Indigenous soil Mn oxide content influenced As speciation and mobilization in paddy soil.•Addition of synthetic Mn oxide decreased reductive As mobilization and As uptake by rice.
Arsenic mobilization in flooded paddy soils correlates with oxalate-extractable As and is also affected by manganese oxides.
Supplier evaluation and selection problem has been studied extensively. Various decision making approaches have been proposed to tackle the problem. In contemporary supply chain management, the ...performance of potential suppliers is evaluated against multiple criteria rather than considering a single factor-cost. This paper reviews the literature of the multi-criteria decision making approaches for supplier evaluation and selection. Related articles appearing in the international journals from 2000 to 2008 are gathered and analyzed so that the following three questions can be answered: (i) Which approaches were prevalently applied? (ii) Which evaluating criteria were paid more attention to? (iii) Is there any inadequacy of the approaches? Based on the inadequacy, if any, some improvements and possible future work are recommended. This research not only provides evidence that the multi-criteria decision making approaches are better than the traditional cost-based approach, but also aids the researchers and decision makers in applying the approaches effectively.
Obesity is a major contributor to the development of steatohepatitis and fibrosis from nonalcoholic fatty liver disease (NAFLD). Hypoxia aggravates progression of NAFLD. In mice on high‐fat diet ...(HFD), hepatic steatosis leads to liver tissue hypoxia, evidenced by accumulation of hypoxia inducible factor‐1‐alpha (HIF‐1α), which is a central regulator of the global response to hypoxia. Hepatocyte cell signaling is an important factor in hepatic fibrogenesis. We here hypothesize that HIF‐1α knockout in hepatocyte may protect against liver fibrosis. We first found that HFD led to 80% more hepatic collagen deposition than Hif1a−/−hep mice, which was confirmed by a‐SMA staining of liver tissue. Body weight and liver weight were similar between groups. We then found the increasing HIF1a expression and decreasing PTEN expression in the mice on HFD and in PA‐treated HepG2 cells. Finally, we found that HIF1 mediated PTEN/nfkb‐p65 pathway plays an important role in the development of NAFLD to liver fibrosis. Collectively, these results identify a novel HIF1a/PTEN/NF‐κ Bp65 signaling pathway in NAFLD, which could be targeted for the therapy.
The results of this study collectively identify a novel Hif1a/PTEN/NF‐κ Bp65 signaling pathway in NAFLD induced by high‐fat‐diet that could be targeted for the therapy.
We investigate whether and when highly trained human capital constitutes a rent-sustaining resource. Our study of 444 CEOs celebrated on the covers of major U.S. business magazines found an advantage ...accruing to graduates of selective universities. Such CEOs led firms with higher and more sustained market valuations. The advantage was strongest for undergraduate programs as these related to the kinds of talent demanded of a CEO. The advantage also was greatest in smaller firms where CEO discretion might be highest and for younger CEOs who may benefit most from college and are less able to appropriate rents. Finally, the advantage accrued to graduates of more recent years, when selective schools had become less socially elitist and increasingly meritocratic, thus favoring human versus social capital.
Proteolysis-targeting chimera (PROTAC) is a heterobifunctional molecule. Typically, PROTAC consists of two terminals which are the ligand of the protein of interest (POI) and the specific ligand of ...E3 ubiquitin ligase, respectively, via a suitable linker. PROTAC degradation of the target protein is performed through the ubiquitin–proteasome system (UPS). The general process is that PROTAC binds to the target protein and E3 ligase to form a ternary complex and label the target protein with ubiquitination. The ubiquitinated protein is recognized and degraded by the proteasome in the cell. At present, PROTAC, as a new type of drug, has been developed to degrade a variety of cancer target proteins and other disease target proteins, and has shown good curative effects on a variety of diseases. For example, PROTACs targeting AR, BR, BTK, Tau, IRAK4, and other proteins have shown unprecedented clinical efficacy in cancers, neurodegenerative diseases, inflammations, and other fields. Recently, PROTAC has entered a phase of rapid development, opening a new field for biomedical research and development. This paper reviews the various fields of targeted protein degradation by PROTAC in recent years and summarizes and prospects the hot targets and indications of PROTAC.
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Periodontitis is an inflammatory disease induced by complex interactions between host immune system and plaque microorganism. Alveolar bone resorption caused by periodontitis is ...considered to be one of the main reasons for tooth loss in adults. To terminate the alveolar bone resorption, simultaneous anti-inflammation and periodontium regeneration is required, which has not appeared in the existing methods. In this study, chitosan (CS), β-sodium glycerophosphate (β-GP), and gelatin were used to prepare an injectable and thermosensitive hydrogel, which could continuously release aspirin and erythropoietin (EPO) to exert pharmacological effects of anti-inflammation and tissue regeneration, respectively. The releasing profile showed that aspirin and EPO could be continuously released from the hydrogels, which exhibited no toxicity both in vitro and in vivo, for at least 21 days. Immunohistochemistry staining and micro-CT analyses indicated that administration of CS/β-GP/gelatin hydrogels loaded with aspirin/EPO could terminate the inflammation and recover the height of the alveolar bone, which is further confirmed by histological observations. Our results suggested that CS/β-GP/gelatin hydrogels are easily prepared as drug-loading vectors with excellent biocompatibility, and the CS/β-GP/gelatin hydrogels loaded with aspirin/EPO are quite effective in anti-inflammation and periodontium regeneration, which provides a great potential candidate for periodontitis treatment in the dental clinic.
Statement of Significance
To terminate the alveolar bone resorption caused by periodontitis, simultaneous anti-inflammation and periodontium regeneration is required, which has not appeared in the existing methods. Here, (1) the chitosan (CS)/β-sodium glycerophosphate/gelatin hydrogels loaded with aspirin/erythropoietin (EPO) can form at body temperature in 5 min with excellent biocompatibility in vitro and in vivo; (2) The faster release of aspirin than EPO in the early stage is beneficial for anti-inflammation and provides a microenvironment for ensuring the regeneration function of EPO in the following step. In vivo experiments revealed that the hydrogels are effective in the control of inflammation and regeneration of the periodontium. These results indicate that our synthesized hydrogels have a great potential in the future clinical application.
MicroRNAs (miRNAs) are short noncoding RNAs that play crucial roles in tumorigenesis and tumor progression. Melanoma is the most aggressive skin cancer that is resistant or rapidly develops ...resistance to a variety of chemotherapeutic agents. The role of miRNAs in melanoma progression and drug resistance has not been well studied. Herein, we demonstrate that miR-200c is down-regulated in melanomas (primary and metastatic) compared with melanocytic nevi. Overexpression of miR-200c in melanoma cells resulted in significantly decreased cell proliferation and migratory capacity as well as drug resistance. miR-200c overexpression resulted in significant down-regulation of BMI-1, ABCG2, ABCG5, and MDR1 expression and in a concomitant increase in E-cadherin levels. Knockdown of BMI-1 showed similar effects as miR-200c overexpression in melanoma cells. In addition, miR-200c overexpression significantly inhibited melanoma xenograft growth and metastasis in vivo , and this correlated with diminished expression of BMI-1 and reduced levels of E-cadherin in these tumors. The effects of miR-200c on melanoma cell proliferation and migratory capacity and on self-renewal were rescued by overexpression of Bmi-1, and the reversal of these phenotypes correlated with a reduction in E-cadherin expression and increased levels of ABCG2, ABCG5, and MDR1. Taken together, these findings demonstrate a key role for miR-200c in melanoma progression and drug resistance. These results suggest that miR-200c may represent a critical target for increasing melanoma sensitivity to clinical therapies.
The real-time reverse transcription-polymerase chain reaction (RT-PCR) detection of viral RNA from sputum or nasopharyngeal swab had a relatively low positive rate in the early stage of coronavirus ...disease 2019 (COVID-19). Meanwhile, the manifestations of COVID-19 as seen through computed tomography (CT) imaging show individual characteristics that differ from those of other types of viral pneumonia such as influenza-A viral pneumonia (IAVP). This study aimed to establish an early screening model to distinguish COVID-19 from IAVP and healthy cases through pulmonary CT images using deep learning techniques. A total of 618 CT samples were collected: 219 samples from 110 patients with COVID-19 (mean age 50 years; 63 (57.3%) male patients); 224 samples from 224 patients with IAVP (mean age 61 years; 156 (69.6%) male patients); and 175 samples from 175 healthy cases (mean age 39 years; 97 (55.4%) male patients). All CT samples were contributed from three COVID-19-designated hospitals in Zhejiang Province, China. First, the candidate infection regions were segmented out from the pulmonary CT image set using a 3D deep learning model. These separated images were then categorized into the COVID-19, IAVP, and irrelevant to infection (ITI) groups, together with the corresponding confidence scores, using a location-attention classification model. Finally, the infection type and overall confidence score for each CT case were calculated using the Noisy-OR Bayesian function. The experimental result of the benchmark dataset showed that the overall accuracy rate was 86.7% in terms of all the CT cases taken together. The deep learning models established in this study were effective for the early screening of COVID-19 patients and were demonstrated to be a promising supplementary diagnostic method for frontline clinical doctors.
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