Hedgehog (Hh) signaling is a highly conserved pathway that plays a vital role during embryonic development. Recently, uncontrolled activation of this pathway has been demonstrated in various types of ...cancer. Therefore, Hh pathway inhibitors have emerged as an important class of anti-cancer agents. Unfortunately, however, their reputation has been tarnished by the emergence of resistance during therapy, necessitating clarification of mechanisms underlying the drug resistance. In this review, we briefly overview canonical and non-canonical Hh pathways and their inhibitors as targeted cancer therapy. In addition, we summarize the mechanisms of resistance to Smoothened (SMO) inhibitors, including point mutations of the drug binding pocket or downstream molecules of SMO, and non-canonical mechanisms to reinforce Hh pathway output. A distinct mechanism involving loss of primary cilia is also described to maintain GLI activity in resistant tumors. Finally, we address the main strategies to circumvent the drug resistance. These strategies include the development of novel and potent inhibitors targeting different components of the canonical Hh pathway or signaling molecules of the non-canonical pathway. Further studies are necessary to avoid emerging resistance to Hh inhibitors and establish an optimal customized regimen with improved therapeutic efficacy to treat various types of cancer, including basal cell carcinoma.
PurposeThis study aims at analysing the causal crowding-out effect of tobacco spending on intrahousehold budget share in Vietnam. Besides, we also examine the differences in expenditure patterns ...between tobacco spending households and non-spending households in Vietnam as well as determine the reason behind these differences.MethodsWe estimated a system of quadratic conditional Engel curve to determine intrahousehold resource allocation using the latest Vietnam Household Living Standard Survey data in 2016. In order to estimate the causal crowding-out effect of tobacco spending, GMM 3SLS method is used to simultaneously deal with heteroscedasticity and endogeneity problems.ResultsAlthough the Wald test results propose the difference in preferences between tobacco spending and non-spending households in Vietnam, once controlling for household characteristics, the results from GMM 3SLS method show that the differences are insignificant. Generally, the crowding-out effect of tobacco spending in Vietnamese households is modest because of the small share of tobacco in the total household expenditure. An increase in tobacco expenditure only leads to a fall in the budget shares of education. The crowding-out effect, however, mainly appears in the case of low-income households.ConclusionsThe reduction in education caused by tobacco consumption, particularly in low-income households, may extend inequality and thus prevent the socioeconomic development in Vietnam in the long term. Additionally, the tiny share of tobacco in household expenditure reveals that the price of tobacco products in Vietnam is extremely low, leading to high proportion of tobacco smokers. Government, therefore, should continuously increase the tobacco tax so that it could restrict the tobacco affordability.
•UCS of concrete is predicted using the extreme gradient boosting regression method.•ANN and SVM methods are considered to compare with the XGB method.•A relevant laboratory measurement dataset ...available in literature is considered.•The XGB method is more robust, faster to train and more accurate than other methods.
The uniaxial compressive strength (UCS) is one of the most important mechanical properties of concrete. This paper aims to demonstrate that the UCS of concrete can be accurately predicted from its compositions and age using the extreme gradient boosting regression (XGB) method. The artificial neural networks (ANN) and the support vector machine (SVM) methods are also considered to compare with the XGB method. A relevant laboratory measurement dataset available in literature is considered to train and test the machine learning (ML) methods. We observe that all the three considered ML methods provide accurate results. However, the XGB method is more robust, faster to train and more accurate than the ANN and SVM methods as well as other existent ML methods presented in literature.
Recurrent conditional heteroskedasticity Nguyen, Trong‐Nghia; Tran, Minh‐Ngoc; Kohn, Robert
Journal of applied econometrics (Chichester, England),
August 2022, Letnik:
37, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Summary
We propose a new class of financial volatility models, called the REcurrent Conditional Heteroskedastic (RECH) models, to improve both in‐sample analysis and out‐of‐sample forecasting of the ...traditional conditional heteroskedastic models. In particular, we incorporate auxiliary deterministic processes, governed by recurrent neural networks, into the conditional variance of the traditional conditional heteroskedastic models, for example, GARCH‐type models, to flexibly capture the dynamics of the underlying volatility. RECH models can detect interesting effects in financial volatility overlooked by the existing conditional heteroskedastic models such as the GARCH, GJR, and EGARCH. The new models often have good out‐of‐sample forecasts while still explaining well the stylized facts of financial volatility by retaining the well‐established features of econometric GARCH‐type models. These properties are illustrated through simulation studies and applications to 31 stock indices and exchange rate data. An user‐friendly software package, together with the examples reported in the paper, is available at https://github.com/vbayeslab.
This work presents a modified solid isotropic material with penalization (SIMP) for conducting dynamic-constrained multi-material topology optimization (MMTO) of thermoelastic structures subjected to ...transient thermal conduction. The novelty of this study is the multi-material optimization of instantaneous temperature conduction under specific frequency constraints, which has never been studied before. The proposed method has been developed for general models of multi-material interpolations such as thermal stiffness, heat capacity, and thermal stress coefficient. The temperature environment is formulated by applying prescribed mechanical and thermal loads that are exposed over a period of time. In this work, we focus on the objective of minimizing compliance in a transient heat conduction structure while simultaneously imposing constraints on the dynamics. With high temperatures, the stiffness of the optimization results decreases while stability is still guaranteed. The sensitivity of the objective function is subsequently calculated using the discretize-then-differentiate approach for the dynamic problem as well as the adjoint variable method. This study examines the impact of thermal fields and different time increments in conjunction with dynamic criteria. The outcomes of heat conduction result in notable alterations under identical dynamic constraint levels.
Background
The aim of this research was to describe the patterns of consumption of multiple sugar‐sweetened beverages (including modern and traditional ones) among adolescents in Ho Chi Minh City and ...to identify a possible relationship between this consumption and overweight, obesity, and other factors.
Methods
A secondary analysis from a cross‐sectional study of 11–15‐year‐old students from 31 junior high schools across Ho Chi Minh City was used. We measured the students’ anthropometric status and assessed beverage consumption using a validated Food Frequency Questionnaire. Multivariate logistic regression models were used to identify the association between the consumption of sugar‐sweetened beverages, obesity and other factors.
Results
The sugar‐sweetened beverages (SSB) ranged widely from modern soft drinks and powdered drinks to traditional sugar‐added fruit and leaf juices, and milk‐based drinks. These beverages were very popular among 2,660 participants with 36% consuming at least one variety daily. Factors positively associated with sugar‐sweetened beverage consumption included a higher level of physical activity, higher consumption of fast foods, and daily fruit and vegetable consumption. We found a negative association between milk‐based SSBs and the overweight and obesity status of the students, i.e. every kcal more of fresh milk with sugar and condensed milk can reduce an obesity odd of 0.005 (95% CI 0.002–0.008, p < 0.001) and 0.004 (95% CI 0.002–0.010, p = 0.044) consecutively. None of the other SSBs was significantly related to adolescent overweight and obesity.
Conclusions
Milk‐based drinks potentially protect adolescents against overweight and obesity. Further research to assess this protection is needed.
•Ag/GO was successfully synthesized by co-precipitation.•LAA was used as a reducing agent, which is easy to find, and eco-friendly.•AgNPs with size 17.65 ± 4.76 nm were decorated on GO.•Concentration ...and contact time significantly affect the antibacterial activity.•The antibacterial activity of Ag/GO increased when pH value was decreased.
Herein, silver/graphene oxide (Ag/GO) nanocomposite was fabricated by co-precipitation with green reducing agent and then was characterized with modern analytical techniques. The antibacterial activities were conducted via the effects of Ag/GO concentration, time, and pH. Results show that silver nanoparticles were uniformly distributed on the GO sheets nanosized of 17.65 ± 4.76 nm. The antibacterial performance was optimized at pH 5.6, eradicating P. aeruginosa in 180 min at 50 µg/mL Ag/GO concentration and S. aureus in 480 min at 300 µg/mL Ag/GO. This demonstrates the potential of Ag/GO as an antibacterial nanocomposite material.
BACKGROUND:Probiotics are the most frequently prescribed treatment for children hospitalized with diarrhea in Vietnam. We were uncertain of the benefits of probiotics for the treatment of acute ...watery diarrhea in Vietnamese children.
METHODS:We conducted a double-blind, placebo-controlled, randomized trial of children hospitalized with acute watery diarrhea in Vietnam. Children meeting the inclusion criteria (acute watery diarrhea) were randomized to receive either 2 daily oral doses of 2 × 10 CFUs of a local probiotic containing Lactobacillus acidophilus or placebo for 5 days as an adjunct to standard of care. The primary end point was time from the first dose of study medication to the start of the first 24-hour period without diarrhea. Secondary outcomes included the total duration of diarrhea and hospitalization, daily stool frequency, treatment failure, daily fecal concentrations of rotavirus and norovirus, and Lactobacillus colonization.
RESULTS:One hundred and fifty children were randomized into each study group. The median time from the first dose of study medication to the start of the first 24-hour diarrhea-free period was 43 hours (interquartile range, 15–66 hours) in the placebo group and 35 hours (interquartile range, 20–68 hours) in the probiotic group (acceleration factor 1.09 95% confidence interval, 0.78–1.51; P = 0.62). There was also no evidence that probiotic treatment was efficacious in any of the predefined subgroups nor significantly associated with any secondary end point.
CONCLUSIONS:This was a large double-blind, placebo-controlled trial in which the probiotic underwent longitudinal quality control. We found under these conditions that L. acidophilus was not beneficial in treating children with acute watery diarrhea.
ZnO/graphene oxide (ZnO/GO) nanocomposites were synthesized by hydrothermal method using zinc acetate and graphite as precursors. Properties of synthesized materials were investigated by different ...physico-chemical techniques and their photocatalytic performance was evaluated with the aid of the photodegradation of methyl orange under UV irradiation. Impacts of reaction conditions such as pH of solutions, catalyst loading and initial concentration on photodegradation rate of synthesized photocatalysts were also investigated. TEM images showed that the average size of the synthesized ZnO was approximately 35 nm, being in good agreement with the obtained XRD results which revealed good dispersion of ZnO particles over the wrinkled GO layers. UV–Vis absorption spectra of these synthesized materials revealed that 5% ZnO/GO exhibited the highest visible light absorption. Photocatalytic experimental results showed that the highest photodegradation rates occurred in a neutral solution with an initial methyl orange (MO) concentration of 10 mg/L. After 2 h of reaction under UV irradiation, more than 95% of MO was degraded at optimal conditions. The photodegradation of MO followed the pseudo-first-order kinetics with apparent reaction rate constants in the range of 0.009–0.030 (min
−1
). ZnO/GO photocatalyst was relatively stable in neutral aqueous solutions during the photodegradation of MO, with a decrease of 6% in photocatalytic performance observed after four cycles compared with the first cycle.
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