Due to the circadian rhythm regulation of almost every biological process in the human body, physiological and biochemical conditions vary considerably over the course of a 24-h period. Thus, optimal ...drug delivery and therapy should be effectively controlled to achieve the desired therapeutic plasma concentrations and therapeutic drug responses at the required time according to chronopharmacological concepts, rather than continuous maintenance of constant drug concentrations for an extended time period. For many drugs, it is not always necessary to constantly deliver a drug into the human body under disease conditions due to rhythmic variations. Pulsatile drug delivery systems (PDDSs) have been receiving more attention in pharmaceutical development by providing a predetermined lag period, followed by a fast or rate-controlled drug release after application. PDDSs are characterized by a programmed drug release, which may release a drug at repeatable pulses to match the biological and clinical needs of a given disease therapy.
This review article focuses on thermoresponsive gating membranes embedded with liquid crystals (LCs) for transdermal drug delivery using PDDS technology. In addition, the principal rationale and the advanced approaches for the use of PDDSs, the marketed products of chronotherapeutic DDSs with pulsatile function designed by various PDDS technologies, pulsatile drug delivery designed with thermoresponsive polymers, challenges and opportunities of transdermal drug delivery, and novel approaches of LC systems for drug delivery are reviewed and discussed. A brief overview of all academic research articles concerning single LC- or binary LC-embedded thermoresponsive membranes with a switchable on-off permeation function through topical application by an external temperature control, which may modulate the dosing interval and administration time according to the therapeutic needs of the human body, is also compiled and presented. In the near future, since thermal-based approaches have become a well-accepted method to enhance transdermal delivery of different water-soluble drugs and macromolecules, a combination of the thermal-assisted approach with thermoresponsive LCs membranes will have the potential to improve PDDS applications but still poses a great challenge.
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•A group evidential reasoning approach based on expert reliability is developed.•Reliability of an expert in a group is measured.•Incomplete assessments are handled to form interval-valued expert ...reliabilities.•Weights and reliabilities of attributes and experts are included in the method.•The proposed method is used to analyze an industry evaluation problem.
The reliability of an expert is an important concept in multiple attribute group decision analysis (MAGDA). However, reliability is rarely considered in MAGDA, or it may be simply assumed that all experts are fully reliable and thus their reliabilities do not need to be considered explicitly. In fact, any experts can only be bounded rational and their various degrees of reliabilities may significantly influence MAGDA results. In this paper, we propose a new method based on the evidential reasoning rule to explicitly measure the reliability of each expert in a group and use expert weights and reliabilities to combine expert assessments. Two sets of assessments, i.e., original assessments and updated assessments provided after group analysis and discussion are taken into account to measure expert reliabilities. When the assessments of some experts are incomplete while global ignorance is incurred, pairs of optimization problems are constructed to decide interval-valued expert reliabilities. The resulting expert reliabilities are applied to combine the expert assessments of alternatives on each attribute and then to generate the aggregated assessments of alternatives. An industry evaluation problem in Wuhu, a city in Anhui Province of China is analyzed by using the proposed method as a real case study to demonstrate its detailed implementation process, validity, and applicability.
•A group consensus method based on expert weight and reliability is proposed.•Expert reliability in multi-round of group analysis and discussion is constructed.•Hybrid weight is measured dynamically ...based on expert reliability.•Convergence of group consensus is accelerated based on hybrid weight.•Evaluation of safety performance is investigated using the proposed method.
Multi-criteria group decision making (MCGDM) as a key module in a group decision support system has attracted much attention. Different experts in MCGDM may hold different decision interests. To generate the solution that is accepted by most experts, a group consensus reaching process has been widely applied in MCGDM along with multiple rounds of group analysis and discussion (GAD). How to characterize the dynamic variation of experts’ opinions in the above process is a critical issue. To solve this problem, expert reliability is defined by measuring the dynamic variation of the support degree from other experts in GAD. By considering expert reliability and expert weight simultaneously, a group consensus measure is proposed and a group feedback mechanism is constructed to accelerate the convergence of group consensus. The dynamic variation of experts’ opinions, especially their non-cooperative behaviors, can be well addressed by using the constructed feedback mechanism. The proposed group consensus reaching process including the group consensus measure and feedback mechanism is applied to solve a problem of evaluating the safety performance of an enterprise located in Changzhou, a city in Jiangsu Province, China, in order to verify its applicability and effectiveness in MCGDM.
The load data in smart grid contains a lot of valuable knowledge, which is useful for both electricity producers and consumers. Load classification is an important issue in load data mining. A ...five-stage process model of load classification is constructed based on the summary and analysis of studies about load classification in smart grid environment. Then, the commonly used clustering methods for load classification are summarized and briefly reviewed, and the well-known evaluation methods for load classification are also introduced. Besides, the applications of load classification, including bad data identification and correction, load forecasting and tariff setting, are discussed. Finally, an example of load classification based on Fuzzy c-means (FCM) is presented.
From genome-wide association studies, brain-derived neurotrophic factor (BDNF) locus on chromosome 11 was the only SNP associated with both smoking and body mass index (BMI) in European, African and ...Asian population. This study aims to explore the unique genetic predisposition to obesity in former smokers by examining the effects of BDNF on BMI and waist circumference (WC).
The study design is case-control study with a cohort validation in supplementary. We included 15,072 ethnic Chinese participants in the Guangzhou Biobank Cohort Study (GBCS) with data of four BDNF SNPs related to both BMI and smoking behavior. We used baseline smoke exposure data in 2003-2007 and follow-up outcomes of general obesity (by BMI) and central obesity (WC) in 2008-2012. Odds ratios (ORs) and 95% confidence intervals (CIs) for general obesity and central obesity associated with these SNPs were derived from logistic regression.
Of 15,072 participants (3169 men and 11,903 women), 1664 (11.0%) had general and 7868 (52.2%) had central obesity. In 1233 former smokers, the rs6265 GG, versus AA, genotype was associated with higher risks of general obesity (OR = 1.79, 95% CI = 1.06-3.01) and central obesity (OR = 2.08, 95% CI = 1.47-2.92) after adjustment. These associations were not significant in never or current smokers. In former heavy (≥20 cigarettes/day) smokers, the rs6265 GG genotype showed a higher odds for general obesity (OR = 2.15, 95% CI = 1.05-4.40), while no association was found in former light (1-9 cigarettes/day) smokers. Similar results were found for the association of rs6265 with central obesity and for the associations of other two BDNF SNPs (rs4923457 and rs11030104) with both general and central obesity.
We firstly identified the genetic predisposition (BDNF SNPs) to general and central obesity in former smokers, particularly in former heavy smokers. The different associations of the SNPs for general/central obesity in different smoke exposure groups may be related to the competitive performance of the sites and epigenetic modification, which needs further study.
Floquet states, where a periodic optical field coherently drives electrons in solids1–3, can enable novel quantum states of matter4–6. A prominent approach to realize Floquet states is based on the ...optical Stark effect. Previous studies on the optical Stark effect often treated the excited state in solids as free quasi-particles3,7–12. However, exciton–exciton interactions can be sizeably enhanced in low-dimensional systems and may lead to light–matter interactions that are qualitatively different from those in the non-interacting picture. Here we use monolayer molybdenum diselenide (MoSe2) as a model system to demonstrate that the driving optical field can couple a hierarchy of excitonic states, and the many-body inter-valley biexciton state plays a dominant role in the optical Stark effect. Specifically, the exciton–biexciton coupling in monolayer MoSe2 breaks down the valley selection rules based on the non-interacting exciton picture. The photon-dressed excitonic states exhibit an energy redshift, splitting or blueshift as the driving photon frequency varies below the exciton transition. We determine a binding energy of 21 meV for the inter-valley biexciton and a transition dipole moment of 9.3 debye for the exciton–biexciton transition. Our study reveals the crucial role of many-body effects in coherent light–matter interaction in atomically thin two-dimensional materials.
Solid-state mechanochemical grinding is important for promoting cocrystal formation, particularly in the design of new solids in the pharmaceutical industry. Pharmaceutical cocrystals are defined as ...crystalline materials comprising an active pharmaceutical ingredient (API) and one or more appropriate coformers in a definite stoichiometric ratio, formed via non-covalent interactions. Recently, both the US FDA (2013) and the EU EMA (2015) provided a Guidance for Industry and a Reflection Paper, respectively, emphasizing that cocrystals are a new type of substance with potential applications in the pharmaceutical industry. This paper contains a brief and systematic overview of pharmaceutical cocrystals prepared by four grinding processes: neat grinding, solvent-assisted grinding, thermal stress after neat grinding, and polymer-assisted grinding. The paper also highlights some examples of pharmaceutical cocrystals prepared by the above grinding approaches, and discusses the stability of cocrystals prepared by mechanical grinding. Also, an overview of cocrystals that are commercially available or undergoing clinical trials is given. A novel methodology for real-time and in situ monitoring of mechanochemical grinding reactions using various analytical techniques is addressed and can be expected to be applied in the near future.
A group consensus reaching process (CRP) based on dynamic expert reliability is proposed in this paper. The method is designed to support uncertain multi-attribute group decision making in situations ...where experts in a group use distributed preference relations (DPRs) to express their preferences when making a decision. In the method, it is assumed that a predefined consensus requirement can be specified and must be satisfied before consensus-based solutions are generated. Consensus measures of DPRs are constructed to ensure consensus convergence and used to check whether the predefined consensus requirement at a specific level is satisfied. If the requirement is not satisfied, expert reliability is first defined and calculated in terms of data depicted by the experts, and then used to design an expert reliability based feedback mechanism composed of identification and suggestion rules to help identify the DPRs hindering CRP. Additionally, experts update their DPRs to accelerate convergence to CRP. Arguably, it is the first attempt to introduce expert reliability in consensus convergence. Once the predefined consensus requirement is satisfied, experts’ preferences are aggregated to generate a consensus-based solution. The problem of selecting an appropriate supplier in a high-end equipment manufacturing enterprise located in Changzhou, Jiangsu Province, China is analyzed by the proposed method to demonstrate its applicability and validity.
Abstract Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ ...on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro . The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7). We found that 24-hour treatment of CQ or HCQ significantly decreased the clonogenic formation in 5637 and T24 cells compared to SV-Huc-1. As human bladder cancer tumor exhibits high basal level of autophagic activities, we detected the autophagic flux in cells treated with CQ and HCQ, showing an alternation in LC3 flux in CQ- or HCQ-treated cells. Moreover, bladder cancer cells treated with CQ and HCQ underwent apoptosis, resulting in increased caspase 3/7 activities, increased level of cleaved poly(ADP-ribose) polymerase (PARP), caspase 3, and DNA fragmentation. Given these results, targeting autophagy with CQ and HCQ represents an effective cancer therapeutic strategy against human bladder cancer.
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