This paper investigates tax incidence resulting from the 'combined unit tax' levied on domestic air travel. Using a panel dataset and estimating with first-differences, I find that domestic aviation ...taxes are over-shifted to passengers by 30-70 cents per dollar tax. A potential nonlinear relationship between tax and fare changes is detected. The results are essential to future studies on tax salience. Seasonal effects are the most pronounced in periods with high demand. I extend the literature by providing fresh evidence of tax incidence in the airline industry and complementing the over-shifting results found in other industries.
Recent literature has documented consumers’ imperfect optimization when facing taxes. Despite the rich literature in this area, little research has been conducted in the airline industry context. I ...exploit the variation of tax changes in the airline industry to analyze how US passengers react to tax and price changes. I show that passengers react more strongly to taxes than to price changes through the use of semi-elasticities. Baseline estimates suggest that the tax elasticity of demand is approximately 1.5 times as strong as the price elasticity of demand. This paper extends the literature by allowing for heterogeneous price and tax responses, and by providing a series of possible rationales that explain how overoptimization can arise in the airline industry. Tax aversion, media coverage, persistent tax increases, psychological factors, and non-standard preferences suggested in the literature could all contribute to explaining passengers’ overoptimization in the airline industry. The findings in this paper have profound contributions both to the economic literature, to the airline industry, and practitioners at both the local and federal levels.
Objectives This study sought to derive and validate outcome-driven thresholds of central blood pressure (CBP) for diagnosing hypertension. Background Current guidelines for managing patients with ...hypertension mainly rely on blood pressure (BP) measured at brachial arteries (cuff BP). However, BP measured at the central aorta (central BP CBP) may be a better prognostic factor for predicting future cardiovascular events than cuff BP. Methods In a derivation cohort (1,272 individuals and a median follow-up of 15 years), we determined diagnostic thresholds for CBP by using current guideline-endorsed cutoffs for cuff BP with a bootstrapping (resampling by drawing randomly with replacement) and an approximation method. To evaluate the discriminatory power in predicting cardiovascular outcomes, the derived thresholds were tested in a validation cohort (2,501 individuals with median follow-up of 10 years). Results The 2 analyses yielded similar diagnostic thresholds for CBP. After rounding, systolic/diastolic threshold was 110/80 mm Hg for optimal BP and 130/90 mm Hg for hypertension. Compared with optimal BP, the risk of cardiovascular mortality increased significantly in subjects with hypertension (hazard ratio: 3.08, 95% confidence interval: 1.05 to 9.05). Of the multivariate Cox proportional hazards model, incorporation of a dichotomous variable by defining hypertension as CBP ≥130/90 mm Hg was associated with the largest contribution to the predictive power. Conclusions CBP of 130/90 mm Hg was determined to be the cutoff limit for normality and was characterized by a greater discriminatory power for long-term events in our validation cohort. This report represents an important step toward the application of the CBP concept in clinical practice.
Lung cancer is the leading cause of cancer‐associated death, with a global 5‐year survival rate <20%. Early metastasis and recurrence remain major challenges for lung cancer treatment. The stemness ...property of cancer cells has been suggested to play a key role in cancer plasticity, metastasis and drug‐resistance, and is a potential target for drug development. In this study, we found that in non‐small cell lung cancer (NSCLC), BMI1 and MCL1 play crucial roles of cancer stemness including invasion, chemo‐resistance and tumour initiation. JNK signalling serves as a link between oncogenic pathway or genotoxicity to cancer stemness. The activation of JNK, either by mutant EGFR or chemotherapy agent, stabilized BMI1 and MCL1 proteins through suppressing the expression of E3‐ubiquitin ligase HUWE1. In lung cancer patient samples, high level of BMI1 is correlated with poor survival, and the expression of BMI1 is positively correlated with MCL1. A novel small‐molecule, BI‐44, was developed, which effectively suppressed BMI1/MCL1 expressions and inhibited tumour formation and progression in preclinical models. Targeting cancer stemness mediated by BMI1/MCL1 with BI‐44 provides the basis for a new therapeutic approach in NSCLC treatment.
Transcription factors involve many proteins in the process of transactivating or transcribing (none-) encoded DNA to initiate and regulate downstream signals, such as RNA polymerase. Their unique ...characteristic is that they possess specific domains that bind to specific DNA element sequences called enhancer or promoter sequences. Epithelial-mesenchymal transition (EMT) is involved in cancer progression. Many dysregulated transcription factors-such as Myc, SNAIs, Twists, and ZEBs-are key drivers of tumor metastasis through EMT regulation. This review summarizes currently available evidence related to the oncogenic role of classified transcription factors in EMT editing and epigenetic regulation, clarifying the roles of the classified conserved transcription factor family involved in the EMT and how these factors could be used as therapeutic targets in future investigations.
Hypoxia, a common process during tumor growth, can lead to tumor aggressiveness and is tightly associated with poor prognosis. Long noncoding RNAs (lncRNAs) are long ribonucleotides (>200 bases) with ...limited ability to translate proteins, and are known to affect many aspects of cellular function. One of their regulatory mechanisms is to function as a sponge for microRNA (miRNA) to modulate its biological functions. Previously,
was identified as a hypoxia-induced lncRNA. However, the regulatory mechanism and functions of
in breast cancer are still unclear. Therefore, we explored whether
can regulate the functions of breast cancer cells through miRNAs. Our results showed the expression levels of
were significantly up-regulated under hypoxia and regulated by HIF-1α and HIF-2α. Next, in contrast to previous reports, nuclear and cytoplasmic fractionation assays and fluorescence
hybridization indicated that
was mainly located in the cytoplasm. Therefore, the labeling of
as a nuclear marker should be done with the caveat. Furthermore, expression levels of miRNAs and RNA immunoprecipitation using antibody against AGO2 showed that
functioned as a sponge of miRNA
. Lastly, functional assays revealed that
could promote cellular migration and proliferation of breast cancer cells. Our findings provide evidence that hypoxia-responsive long non-coding
could be transcriptionally activated by HIF-1α and HIF-2α, act as a miRNA sponge of
, and promote tumor growth and migration in breast cancer cells. These data suggest that
may be a candidate for therapeutic targeting of breast cancer progression.
The site selectivity for lysine conjugation on a native protein is difficult to control and characterize. Here, we applied mass spectrometry to examine the conjugation kinetics of Trastuzumab-IgG ...(Her-IgG) and α-lactalbumin under excess linker concentration (L
) based on the modified Michaelis-Menten equation, in which the initial rate constant per amine (k
= V
/K
) was determined by the maximum reaction rate (V
) under saturated accessible sites and initial amine-linker affinity (1/K
). Reductive amination (RA) displayed 3-4 times greater V
and a different panel of conjugation sites than that observed for N-hydroxysuccinimide ester (NHS) chemistry using the same length of polyethylene glycol (PEG) linkers. Moreover, faster conversion power rendered RA site selectivity among accessible amine groups and a greater tunable range of linker/protein ratio for aldehyde-linkers compared to those of the same length of NHS-linkers. Single conjugation with high yield or poly-conjugations with site homogeneity was demonstrated by controlling L
or gradual addition to minimize the L
/K
ratio. Formaldehyde, the shortest aldehyde-linker with the greatest 1/K
, exhibited the highest selectivity and was shown to be a suitable probe to predict conjugation profile of aldehyde-linkers. Four linkers on the few probe-predicted hot spots were elucidated by kinetically controlled RA with conserved drug efficacy when conjugated with the payload. This study provides insights into controlling factors for homogenous and predictable amine bioconjugation.
Hypoglycemia is associated with serious health outcomes for patients treated for diabetes. However, the outcome of outpatients with type 2 diabetes who have experienced hypoglycemia episodes is ...largely unknown.
The study population, derived from the National Health Insurance Research Database released by the Taiwan National Health Research Institutes during 1998-2009, comprised 77,611 patients with newly diagnosed type 2 diabetes. We designed a prospective study consisting of randomly selected hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without hypoglycemia. We investigated the relationships of hypoglycemia with total mortality and cardiovascular events, including stroke, coronary heart disease, cardiovascular diseases, and all-cause hospitalization.
There were 1,844 hypoglycemic events (500 inpatients and 1,344 outpatients) among the 77,611 patients. Both mild (outpatient) and severe (inpatient) hypoglycemia cases had a higher percentage of comorbidities, including hypertension, renal diseases, cancer, stroke, and heart disease. In multivariate Cox regression models, including diabetes treatment adjustment, diabetic patients with hypoglycemia had a significantly higher risk of cardiovascular events during clinical treatment periods. After constructing a model adjusted with propensity scores, mild and severe hypoglycemia still demonstrated higher hazard ratios (HRs) for cardiovascular diseases (HR 2.09 95% CI 1.63-2.67), all-cause hospitalization (2.51 2.00-3.16), and total mortality (2.48 1.41-4.38).
Symptomatic hypoglycemia, whether clinically mild or severe, is associated with an increased risk of cardiovascular events, all-cause hospitalization, and all-cause mortality. More attention may be needed for diabetic patients with hypoglycemic episodes.
In this work, different ratios of molybdenum carbide (1, 3 and 5 mass% Mo2C) powders were added to Vanadis 4 extra alloy steel powders and then mixed by ball milling for 6 h. The composite powders ...underwent vacuum sintering at 1200, 1220, 1240, 1260 and 1280°C for 1 h, respectively. The results showed that the optimal sintering temperature for the addition of 5 mass% Mo2C powders was 1220°C. It also represented that the apparent porosity was 0.18%, and that a transverse rupture strength (TRS) value of 2281.3 MPa and a hardness value of 79.2 HRA were obtained, respectively. Additionally, the TRS value was obviously enhanced to 2437.6 and 2491.4 MPa by the addition of 5 mass% Mo2C powders after heat treatment and sub-zero plus heat treatments, respectively. Meanwhile, the hardness value also increased to 80.6 and 81.3 HRA, respectively, whereas the Mo-rich M6C carbides distributed in the grain boundaries, and V-rich MC carbides appeared in the grain and grain boundaries after sub-zero plus heat treatments. Significantly, a series of heat treatment processes is effective in improving the microstructure and strengthening the mechanical properties of the sintered Vanadis 4 extra composites.
We developed a smartphone-assisted microchemistry analyzer for the quantitative detection of carbofuran using a paper-based colorimetric sensor, Photoshop software, and a smartphone app. The changes ...in color of the carbofuran enzymatic reaction in the paper-based sensor were captured and analyzed using a smartphone-controlled analyzer with an LED light source and a smartphone camera. The high accuracy of this method was demonstrated for the determination of carbofuran with a linear response in the range 0.05-1.0 ppm and limits of detection (LOD) of 0.02 and 0.018 ppm using Photoshop and smartphone app colorimetric analysis, respectively. These two methods not only show the high sensitivity and highly quantitative relationships between the concentrations of commercial carbofuran and characteristic color values of the blue channel in smartphone images but were also applied to infusions of tea. Moreover, the smartphone app is able to GPS tag the location of the test and transmit the results to a website that displays quantitative results from carbofuran samples on a map.
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