A flapping wing micro air vehicle (FWMAV) demands high lift and thrust generation for a desired payload. In view of this, the present work focuses on a novel way of enhancing the lift characteristics through integrating check-valves in the flapping wing membrane. Modal analysis and static analysis are performed to determine the natural frequency and deformation of the check-valve. Based on the inference, the check-valve opens and closes during the upstroke flapping and downstroke flapping, respectively. Wind tunnel experiments were conducted by considering the two cases of wing design, i.e., with and without a check-valve for various driving voltages, wind speeds and different inclined angles. A 20 cm-wingspan polyethylene terephthalate (PET) membrane wing with two check-valves, composed of central disc-cap with radius of 7.43 mm, supported by three S-beams, actuated by Evans mechanism to have 90° stroke angle, is considered for the 10 gf (gram force) FWMAV study. The aerodynamic performances, such as lift and net thrust for these two cases, are evaluated. The experimental result demonstrates that an average lift of 17 gf is generated for the case where check-valves are attached on the wing membrane to operate at 3.7 V input voltage, 30° inclined angle and 1.5 m/s wind speed. It is inferred that sufficient aerodynamic benefit with 68% of higher lift is attained for the wing membrane incorporated with check-valve. Full article

This paper focuses on the energy generating capacity of polyvinylidene difluoride (PVDF) piezoelectric material through a number of prototype sensors with different geometric and loading characteristics. The effect of sensor configuration, surface area, dielectric thickness, aspect ratio, loading frequency and strain on electrical power output was investigated systematically. Results showed that parallel bimorph sensor was found to be the best energy harvester, with measured capacitance being reasonably acceptable. Power output increased with the increase of sensor’s surface area, loading frequency, and mechanical strain, but decreased with the increase of the sensor thickness. For all scenarios, sensors under flicking loading exhibited higher power output than that under bending. A widely used energy harvesting circuit had been utilized successfully to convert the AC signal to DC, but at the sacrifice of some losses in power output. This study provided a useful insight and experimental validation into the optimization process for an energy harvester based on human movement for future development. Full article

In previously reported experimental studies, a yield of double-walled carbon nanotubes (DWCNTs) at C₇₀@Single-walled carbon nanotubes (SWCNTs) is higher than C₆₀@SWCNTs due to the higher sensitivity to photolysis of the former. From the perspective of pyrolysis dynamics, we would like to understand whether C₇₀@SWCNT is more sensitive to thermal decomposition than C₆₀@SWCNT, and the starting point of DWCNT formation, which can be obtained through the decomposition fragmentation of the nanopeapods, which appears in the early stages. We have studied the fragmentation of C₇₀@SWCNT nanopeapods, using molecular dynamics simulations together with the empirical tight-binding total energy calculation method. We got the snapshots of the fragmentation structure of carbon nano-peapods (CNPs) composed of SWCNT and C₇₀ fullerene molecules and the geometric spatial positioning structure of C₇₀ within the SWCNT as a function of dynamics time (for 2 picoseconds) at the temperatures of 4000 K, 5000 K, and 6000 K. In conclusion, the scenario in which C₇₀@SWCNT transforms to a DWCNT would be followed by the fragmentation of C₇₀, after C₇₀, and the SWCNT have been chemically bonding in the early stages. The relative stability of fullerenes in CNPs could be reversed, compared to the ranking of the relative stability of the encapsulated molecules themselves. Full article

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs, which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring. In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques, the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath, and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63–100%, 90–95%, and 47–97%, respectively) while minimizing stress and discomfort for the patient. Full article

Most causal genes for inherited arrhythmia syndromes (IASs) encode cardiac ion channel-related proteins. Genotype-phenotype studies and functional analyses of mutant genes, using heterologous expression systems and animal models, have revealed the pathophysiology of IASs and enabled, in part, the establishment of causal gene-specific precision medicine. Additionally, the utilization of induced pluripotent stem cell (iPSC) technology have provided further insights into the pathophysiology of IASs and novel promising therapeutic strategies, especially in long QT syndrome. It is now known that there are atypical clinical phenotypes of IASs associated with specific mutations that have unique electrophysiological properties, which raises a possibility of mutation-specific precision medicine. In particular, patients with Brugada syndrome harboring an SCN5A R1632C mutation exhibit exercise-induced cardiac events, which may be caused by a marked activity-dependent loss of R1632C-Nav1.5 availability due to a marked delay of recovery from inactivation. This suggests that the use of isoproterenol should be avoided. Conversely, the efficacy of β-blocker needs to be examined. Patients harboring a KCND3 V392I mutation exhibit both cardiac (early repolarization syndrome and paroxysmal atrial fibrillation) and cerebral (epilepsy) phenotypes, which may be associated with a unique mixed electrophysiological property of V392I-Kv4.3. Since the epileptic phenotype appears to manifest prior to cardiac events in this mutation carrier, identifying KCND3 mutations in patients with epilepsy and providing optimal therapy will help prevent sudden unexpected death in epilepsy. Further studies using the iPSC technology may provide novel insights into the pathophysiology of atypical clinical phenotypes of IASs and the development of mutation-specific precision medicine. Full article

This study investigated whether four single nucleotide polymorphisms (SNPs) moderated caffeine effects on vigilance and performance in a double-blind and crossover total sleep deprivation (TSD) protocol in 37 subjects. In caffeine (2 × 2.5 mg/kg/24 h) or placebo-controlled condition, subjects performed a psychomotor vigilance test (PVT) and reported sleepiness every six hours (Karolinska sleepiness scale (KSS)) during TSD. EEG was also analyzed during the 09:15 PVT. Carriers of the TNF-α SNP A allele appear to be more sensitive than homozygote G/G genotype to an attenuating effect of caffeine on PVT lapses during sleep deprivation only because they seem more degraded, but they do not perform better as a result. The A allele carriers of COMT were also more degraded and sensitive to caffeine than G/G genotype after 20 h of sleep deprivation, but not after 26 and 32 h. Regarding PVT reaction time, ADORA2A influences the TSD effect but not caffeine, and PER3 modulates only the caffeine effect. Higher EEG theta activity related to sleep deprivation was observed in mutated TNF-α, PER3, and COMT carriers, in the placebo condition particularly. In conclusion, there are genetic influences on neurobehavioral impairments related to TSD that appear to be attenuated by caffeine administration. (NCT03859882). Full article

Constructing polymeric materials with stretchable and self-healing properties arise increasing interest in the field of tissue engineering, wearable electronics and soft actuators. Herein, a new type of supramolecular cross-linker was constructed through host-guest interaction between pillar[⁵]arene functionalized acrylate and pyridinium functionalized acrylate, which could form supramolecular polymeric material via photo-polymerization of n-butyl acrylate (BA). Such material exhibited excellent tensile properties, with maximum tensile strength of 3.4 MPa and strain of 3000%, respectively. Moreover, this material can effectively dissipate energy with the energy absorption efficiency of 93%, which could be applied in the field of energy absorbing materials. In addition, the material showed self-healing property after cut and responded to competitive guest. Full article

Dectes texanus larvae girdles the stems of soybean and cultivated sunflowers causing significant yield losses in North America. The soybean Plant Introduction (PI) 165673 exhibits antibiosis resistance to the larval stage. The objectives of this study were: (1) to determine the inheritance of D. texanus resistance in PI165673; (2) evaluate PI165673 antibiosis resistance before 21 d post infestation; (3) evaluate girdling damage in PI16563 at the end of the season. K07-1544/PI165673 F₂ and F_2:3 populations were tested for resistance to D. texanus in 2011 and 2012, and PI165673 antibiosis resistance and girdling damage were evaluated in 2014. Segregation for resistance to D. texanus and heritability estimates in the F₂ and F_2:3 populations indicated that resistance was controlled by two genes with dominant and recessive epistasis. Antibiosis evaluations indicated: (1) PI165673 contained lower number of larvae and eggs relative to the number of oviposition punctures at 15 d post infestation; (2) the proportion of first-instar larvae was higher in PI165673 at 15 d post infestation; (3) larvae reach the sixth-instar stage in PI165673. None of the PI165673 plants were girdled at the end of the season. Identification of additional sources of D. texanus resistance is required to impair larval development in the stem. Full article

Immunotherapy has revolutionized the therapeutic landscape of melanoma. In particular, checkpoint inhibition has shown to increase long-term outcome, and, in some cases, it can be virtually curative. However, the absence of clinically validated predictive biomarkers is one of the major causes of unpredictable efficacy of immunotherapy. Indeed, the availability of predictive biomarkers could allow a better stratification of patients, suggesting which type of drugs should be used in a certain clinical context and guiding clinicians in escalating or de-escalating therapy. However, the difficulty in obtaining clinically useful predictive biomarkers reflects the deep complexity of tumor biology. Biomarkers can be classified as tumor-intrinsic biomarkers, microenvironment biomarkers, and systemic biomarkers. Herein we review the available literature to classify and describe predictive biomarkers for checkpoint inhibition in melanoma with the aim of helping clinicians in the decision-making process. We also performed a meta-analysis on the predictive value of PDL-1. Full article

Background: The use of a touchless automated hand sanitizer dispenser may play a key role to reduce contagious diseases. The key problem of the conventional ultrasonic and infra-red-based dispensers is their malfunctioning due to the interference of sunlight, vehicle sound, etc. when deployed in busy public places. To overcome such limitations, this study introduced a laser-based sensing device to dispense sanitizer in an automated touchless process. Method: The dispensing system is based on an Arduino circuit breadboard where an ATmega328p microcontroller was pre-installed. To sense the proximity, a light-dependent resistor (LDR) is used where the laser light is to be blocked after the placement of human hands, hence produced a sharp decrease in the LDR sensor value. Once the LDR sensor value exceeds the lower threshold, the pump is actuated by the microcontroller, and the sanitizer dispenses through the nozzle. Results and discussion: A novel design and subsequent fabrication of a low-cost, touchless, automated sanitizer dispenser to be used in public places, was demonstrated. The overall performance of the manufactured device was analyzed based on the cost and power consumption, and environmental factors by deploying it in busy public places as well as in indoor environment in major cities in Bangladesh, and found to be more efficient and cost-effective compared to other dispensers available in the market. A comprehensive discussion on this unique design compared to the conventional ultrasonic and infra-red based dispensers, is presented to show its suitability over the commercial ones. The guidelines of the World Health Organization are followed for the preparation of sanitizer liquid. A clear demonstration of the circuitry connections is presented herein, which facilitates the interested individual to manufacture a cost-effective dispenser device in a relatively short time and use it accordingly. Conclusion: This study reveals that the LDR-based automated hand sanitizer dispenser system is a novel concept, and it is cost-effective compared to the conventional ones. The presented device is expected to play a key role in contactless hand disinfection in public places, and reduce the spread of infectious diseases in society. Full article

There has been significant interest in the values and benefits of early childhood nature experiences on children’s well-being and development. One aspect of studying the exposure of children to nature that requires more focus is the role played by early childhood educators. In particular, there is a need for early childhood environmental education training for pre-service educators. This study will explore the use of a UNESCO Biosphere Reserve as an outdoor classroom for early childhood environmental education pre-service professionals. Exploratory quantitative and qualitative descriptive data from a series of three short surveys (pre/post/delayed post) provide a basic overview of pre-service teacher perspectives, experiences, and outcomes of an environmental education intervention. The results indicate that the participating pre-service educators had little to no familiarity with the environmental concepts or the biosphere reserve site before participation in the intervention. The post-intervention and delayed post-intervention results show that pre-service educators perceived that their understanding of the concept had improved. The results also show a perception of the positive role that biosphere reserve sites can play in early childhood education. Three critical implications emerged from the overall quantitative and qualitative results: (1) specific support should be given for early childhood environmental education training; (2) biosphere reserve functions provide support for efforts to improve connections to nature; (3) early childhood education has the potential to support the broadening of the biosphere reserve audience. Full article

As the attitudes of healthcare staff are thought to influence the quality and effectiveness of interventions targeting patients’ suicide risk, attitudes are often used as an outcome in the evaluation of suicide-preventive training. Due to various problems related to the validity and reliability of commonly used scales, there is a lack of overall agreement on how to measure these attitudes. Confirmatory factor analysis (CFA) was used to cross-validate previously used models and to investigate new models to measure professionals’ attitudes toward work with suicidal individuals and to test the longitudinal stability of the models by analyzing new sets of data. The population in the first study consisted of a heterogenous group of 1350 professionals who managed suicidal individuals relatively frequently. The second study included 640 professionals. The results of the cross-validation of previous models were described and a new questionnaire measuring attitudes toward suicide prevention, suicidal individuals, and organizational-facilitated self-efficacy (OSAQ-12) was presented. The three presented models retained a good fit and were stable over time. Valid and reliable measurement models that measure aspects of attitudes toward suicide are a prerequisite for conducting both cross-sectional and intervention studies. Full article

It is widely accepted that chondral defects in articular cartilage of adult joints are never repaired spontaneously, which is considered to be one of the major causes of age-related degenerative joint disorders, such as osteoarthritis. Since mobilization of subchondral bone (marrow) cells and addition of chondrocytes or mesenchymal stromal cells into full-thickness defects show some degrees of repair, the lack of self-repair activity in adult articular cartilage can be attributed to lack of reparative cells in adult joints. In contrast, during a fetal or embryonic stage, joint articular cartilage has a scar-less repair activity, suggesting that embryonic joints may contain cells responsible for such activity, which can be chondrocytes, chondroprogenitors, or other cell types such as skeletal stem cells. In this respect, the tendency of pluripotent stem cells (PSCs) to give rise to cells of embryonic characteristics will provide opportunity, especially for humans, to obtain cells carrying similar cartilage self-repair activity. Making use of PSC-derived cells for cartilage repair is still in a basic or preclinical research phase. This review will provide brief overviews on how human PSCs have been used for cartilage repair studies. Full article

Simulation-based prediction of mechanical properties is highly desirable for optimal choice and treatment of leather. Nowadays, this is state-of-the-art for many man-made materials. For the natural material leather, this task is however much more demanding due to the leather’s high variability and its extremely intricate structure. Here, essential geometric features of the leather’s meso-scale are derived from 3D images obtained by micro-computed tomography and subsumed in a parameterizable structural model. That is, the fiber-bundle structure is modeled. The structure model is combined with bundle properties derived from tensile tests. Then the effective leather visco-elastic properties are simulated numerically in the finite element representation of the bundle structure model with sliding contacts between bundles. The simulation results are validated experimentally for two animal types, several tanning procedures, and varying sample positions within the hide. Finally, a complete workflow for assessing leather quality by multi-scale simulation of elastic and visco-elastic properties is established and validated. Full article

Telomerase is known to contribute to telomere maintenance and to provide cancer cell immortality. However, numerous reports are showing that the function of the enzyme goes far beyond chromosome ends. The study aimed to explore how telomerase downregulation in MCF7 and MDA-MB-231 breast cancer cells affects their ability to survive. Consequently, sensitivity to drug resistance, proliferation, and adhesion were assessed. The lentiviral-mediated human telomerase reverse transcriptase (hTERT) downregulation efficiency was performed at gene expression and protein level using qPCR and Western blot, respectively. Telomerase activity was evaluated using the Telomeric Repeat Amplification Protocol (TRAP) assay. The study revealed that hTERT downregulation led to an increased sensitivity of breast cancer cells to doxorubicin which was demonstrated in MTT and clonogenic assays. During a long-term doubling time assessment, a decreased population doubling level was observed. Interestingly, it did not dramatically affect cell cycle distribution. hTERT downregulation was accompanied by an alteration in β1-integrin- and by focal adhesion kinase (FAK)-driven pathways together with the reduction of target proteins phosphorylation, i.e., paxillin and c-Src. Additionally, autophagy activation was observed in MDA-MB-231 cells manifested by alternations in Atg5, Beclin 1, LC3II/I ratio, and p62. These results provide new evidence supporting the possible therapeutic potential of telomerase downregulation leading to induction of autophagy and cancer cells elimination. Full article

The landscape patterns of plantations (PT) are the results of human disturbances on local vegetation, and in turn, differ greatly from natural forests (NF), since the patterns strongly influence the natural circulation of material and energy. There is a need to understand the differences of landscape patterns between PT and NF, to establish a near natural afforestation strategy. This study chose three typical silvicultural counties in the middle reaches of the Yangtze River as the research areas and compared the landscape patterns of NF and PT, with other land use types (grassland, GL; cropland, CL; shrubland, SL; orchard, OR; built-up land, BUL; bare land, BL; and water bodies, WB). The results revealed that the areas of PT accounted for 7.67%, 12.05%, and 18.97% of three counties, bigger than GL, OC, BUL, BL, and WB, as one of main land use types. The landscape patterns of PT (mean patch size between 2.06 to 6.05 ha) were more fragmented than NF (mean patch size between 5.83 to 53.91 ha). NF areas increased along the relative altitude gradient, from 0 to 2500 m, while PT areas peaked from 100–1000 m. The higher the altitude, the more typical the zonal distribution of PT, the more aggregated the NF. NF had significant negative correlations with BL, BUL, CL, PT, GL, and OC, which suggest that human activities had seriously interfered with NF. Although PT as an ecological protection strategy was increasing, the landscape patterns of PT were obviously different from NF. This may affect the material energy flow in the ecological environment. The results in the present study have great implications in the other regions in China and the relevant parts of the world where natural forests were heavily disturbed. Full article

Southern Ozark Mississippi Valley-type ores are enriched in radiogenic Pb, with isotopic signatures suggesting that metals were supplied by two end-member components. While the less radiogenic component appears to be derived from various shale and sandstone units, the source of the more radiogenic component has not yet been identified. Analyses of cherts from the Early Ordovician Cotter Dolomite and tripolitic chert from the Early Mississippian Boone Formation contain highly radiogenic Pb, with isotopic ratios comparable to those of ores. However, most samples have lower ²⁰⁸Pb/²⁰⁴Pb and ²⁰⁷Pb/²⁰⁴Pb for a given ²⁰⁶Pb/²⁰⁴Pb compared to ores. These relationships demonstrate that the enriched Pb isotopic values of the ore array cannot be related to the host and regional lithologies sampled, suggesting that the source of high ratios may lay further afield. The slope of the linear trend defined by the Pb isotope ratios of ores corresponds to an age of about 1.19 Ga. Therefore, an alternative for the linear array is the involvement of Precambrian basement in supplying ore Pb. Rare earth element patterns show that diagenetic processes involving the action of groundwater and hydrothermal fluids affected the sampled lithologies to various degrees, with Cotter Dolomite having experienced the highest degree of alteration. Full article

Considering the constant increase in breast cancer patients, identifying factors that influence the moment of diagnosis is essential for optimizing therapeutic management and associated cost. The purpose of the study is to evaluate the impact of the economic crisis on the moment of a breast cancer diagnosis. This retrospective observational study analyzed a cohort of 4929 patients diagnosed with breast cancer over the course of 19 years in the Western region of Romania. The time interval was divided based on the onset of the economic crisis into 3 periods: pre-crisis (2001–2006), crisis (2007–2012), and post-crisis (2013–2019). The disease stage at the moment of diagnosis was considered either early (stages 0, I, II) or advanced (stages III, IV). Although recording a similar mean number of patients diagnosed per year during the pre- and crisis periods, a significantly higher percentage of patients were diagnosed with late-stage breast cancer during the economic crisis period compared to the previous interval (46.9% vs. 56.3%, p < 0.01). This difference was further accentuated when accounting for environmental setting, with 65.2% of patients from a rural setting being diagnosed with advanced disease during the crisis interval. An overall improvement of 12% in early-stage breast cancer diagnosis was recorded in the post-crisis period (55.7%, p < 0.001). The findings of this study support periods of economic instability as potential factors for a delay in breast cancer diagnosis and highlight the need for the development of specific strategies aimed at reducing cancer healthcare and associated financial burden in times of economic crisis. Full article

The review is devoted to modern trends in the chemistry of 2-amino and 2-mercapto substituted benzothiazoles covering the literature since 2015. The reviewed heterocycles belong to biologically active and industrially demanded compounds. Newly developed synthesis methods can be divided into conventional multistep processes and оne-pot, atom economy procedures, realized using green chemistry principles and simple reagents. The easy functionalization of the 2-NH₂ and 2-SH groups and the benzene ring of the benzothiazole moiety allows considering them as highly reactive building blocks for organic and organoelement synthesis, including the synthesis of pharmacologically active heterocycles. The review provides a summary of findings, which may be useful for developing new drugs and materials and new synthetic approaches and patterns of reactivity. Full article

Multi-objective evolutionary algorithms (MOEAs) are widely used to optimize multi-purpose reservoir operations. Considering that most outcomes of MOEAs are Pareto optimal sets with a large number of incomparable solutions, it is not a trivial task for decision-makers (DMs) to select a compromise solution for application purposes. Due to the increasing popularity of data-driven decision-making, we introduce a clustering-based decision-making method into the multi-objective reservoir operation optimization problem. Traditionally, solution selection has been conducted based on trade-off ranking in objective space, and solution characteristics in decision space have been ignored. In our work, reservoir operation processes were innovatively clustered into groups with unique properties in decision space, and the trade-off surfaces were analyzed via clustering in objective space. To attain a suitable performance, a new similarity measure, referred to as the Mei–Wang fluctuation similarity measure (MWFSM), was tailored to reservoir operation processes. This method describes time series in terms of both their shape and quantitative variation. Then, a compromise solution was selected via the joint use of two clustering results. A case study of the Three Gorges cascade reservoirs system under small and medium floods was investigated to verify the applicability of the proposed method. The results revealed that the MWFSM effectively distinguishes reservoir operation processes. Two more operation patterns with similar positions but different shapes were identified via MWFSM when compared with Euclidean distance and the dynamic time warping method. Furthermore, the proposed method decreased the selection range from the whole Pareto optimal set to a set containing relatively few solutions. Finally, a compromise solution was selected. Full article

Combining the nuclear resonance fluorescence (NRF) transmission method with computed tomography (CT) can be a novel method for imaging the isotope distributions, which is indispensable in nuclear engineering. We performed an experiment to reconstruct a three-dimensional NRF-CT image with isotope selectivity of enriched lead isotope rods (²⁰⁸Pb) together with a set of different rods, including another enriched isotope (²⁰⁶Pb), iron, and aluminum rods, inserted into a cylindrical aluminum holder. Using a laser Compton scattering (LCS) gamma ray beam with a 5.528 MeV maximum energy, 2 mm beam size, and 10 photon·s⁻¹·eV⁻¹ flux density, which is available at the BL1U beamline in the ultraviolet synchrotron orbital radiation-III (UVSOR-III) synchrotron radiation facility at the Institute of Molecular Science at the National Institutes of Natural Sciences in Japan, and we excited the J^π = 1⁻ NRF level at 5.512 MeV in ²⁰⁸Pb. An isotope-selective three-dimensional NRF-CT image of the ²⁰⁸Pb isotope distribution was experimentally obtained for the first time with a pixel resolution of 4 mm in the horizontal plane. Full article