Colours were ubiquitous in the medieval world, and castles were no exception. While in the eyes of most people their rich colour schemes manifested power and wealth, some could also read the more nuanced messages these colours conveyed. The main objective of this paper is to discuss the use and role of colour in the interiors of castles of medieval Bohemia and Poland. The picture is complemented by the analysis of colour decorations of defensive residences of the Teutonic Order, for which colour schemes of external facades can be addressed as well. The dis-cussion takes into account the varying state of preservation and draws from the available writ-ten accounts. To present the most complete picture possible, we discuss royal residences, for which unfortunately limited data is available, as well as better-preserved castles of dukes and knights. We discuss the identified iconographic programmes and their chivalric, heraldic, and hagiographic motifs. Also within the scope of our discussion are late forms of floral decorations, known as “green chambers”. The numerous examples presented in the paper prove that colour was an important tool of visual social communication in castle architecture: it complemented the symbolism, and sometimes carried an independent message.

There is an overarching need to find alternative treatment options for malaria and this quest is more pressing in current times due to the morbidity and mortality data arising from most endemic countries and partially owing to the fact that the SARS-Cov-2 pandemic has diverted much public health attention. Additionally, the therapeutic options available for malaria has been severely threatened with the emergence of resistance to almost all existing drugs by the human malaria parasite. The Artemisinin Combination Therapies (ACTs) which hitherto have been the mainstay for malaria have encountered resistance in South East Asia, a notorious ground zero for the emergence of antimalarial drug resistance. This review analyses few key druggable targets of the parasite and the potential to leverage strategic inhibitors to mitigate the scourge of malaria by providing a concise assessment of the essential proteins of the malaria parasite that could serve as targets. Furthermore, this work provides a summary of the advances made in malaria parasite biology and the potential to leverage such findings for antimalarial drug production.

Virtual reality (VR) can play a key role in automotive marketing research, lowering costs and shortening the time it takes to bring a new product to market. However, there are still few VR applications that support automotive customers' experiences during the early stages of product development. Through a systematic review of literature and patents, this study aims to identify the challenges and opportunities for the application of virtual reality in car clinics, and to categorize them into attributes. We searched through the knowledge databases of PatentScout, ScienceDirect, Springer, and IEEEXplore. We found 72 patents with a high concentration in a few inventors. The United States of America presented the greatest number of records and the most common applications related to the apparatus for automatically reading respondents' reactions in a virtual environment. In terms of articles, we found 19 research papers that discussed sixteen categories identified as challenges and opportunities for automotive marketing research: 1) cost, 2) location to customers, 3) flexibility in interactions, 4) model transportation, 5) depth perception, 6) haptic perception, 7) motion, 8) movement perception/ physical collision, 9) color and texture, 10) sound feedback, 11) product interaction/manipulation, 12) visual-spatial, 13) graphic quality, 14) intuitiveness, 15) cybersecurity and 16) cybersickness. We conclude that the automotive industry can employ virtual reality for marketing research, but relevant elements such as hardware and software definition, stimulus quality, and research objectives, among others, must be considered.

miRNAs have recently attracted investigators' interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors comprise of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

In this paper we study solutions and drift homogenization for a class of viscous lake equations by using the method of semigroups of bounded operators. Suppose that the initial value i.e.,for some Hölder continuous function onwith smooth function value satisfying and Then the initial value problem (2) for viscous lake equations has a unique smooth local strong solution. Using this result we study the drift homogenization for three-dimensional stationary Stokes equation in the usual sense

The goal is to reduce poverty, the method used is a literature study to see the effect of using Financial Technology (Fintech) on financial inclusion, method to see the effect of financial inclusion on poverty. From the results of the tests, the use of Fintech can increase financial inclusion, thereby encouraging poverty alleviation. It can be seen that the Financial Inclusion variable has a significant and negative effect on the poverty variable. This shows that countries that have high levels of financial inclusion are generally estimated to have low poverty rates. Increasing a country's financial inclusion can reduce poverty.

Neocarya macrophylla (Sabine) Prance (Nm, Chrysobalanaceae) is used traditionally as food, for medicinal spiritual and industrial purposes. It is also used as soap, dye, glue, fodder, termite repellent, firewood and for structural materials. Few studies on the physicochemical, nutritional contents, phytochemical and pharmacological activities have validated the benefits of Nm to humanity as food, in cosmetics and pharmaceutical products. The major bioactive constituents identified in the plant so far are steroids and flavonoids (such as stigmasterol, quercetin, catechin and its related glycosides). Extracts of the plant have shown good antivenom, antimicrobial, analgesic, anti-inflammatory, antimycobacterial, anthelmintic and antioxidant activities. Acute toxicity studies conducted have confirmed the plant to be toxic. More studies on the plant are required in order to exploit other biological activities as claimed by traditional healers and also to isolate more bioactive compounds. In addition, the safety and tolerability assessment of Nm should be undertaken due to its widespread usage.

The evaporation of polymer solution droplet is an important in solution-based polymer film fabrications, such as inkjet print, spray coatings, and droplet casting etc. In this work, we investigated the effect of droplet size, solvent evaporation rate, and concentration on “coffee-ring” effect, crystal nucleation, polymorphism, and morphology of dried poly (vinylidene fluoride) (PVDF) solution droplets with atomic force microscopy (AFM) method. We found that the crystal structure, morphology and crystal distribution in the center and edge regions of dried PVDF droplets were different due to “coffee-ring” effect. The “coffee-ring” effect of dried PVDF droplets was mainly composited of accumulated crystals at the edge region of droplet, which was mainly made by crystallization of migrated chains. The interplay between migration of chains, crystallization and solidification of PVDF droplets significantly influenced the formation of “coffee-ring”. In addition, our results showed that the decrease of droplet size and controlling solvent evaporation rate were effective ways to improve the PVDF β-phase nucleation and decrease crystal size.

Background: HMGA2 encodes a small non histone chromatin-associated protein that has no intrinsic transcriptional activity, but can modulate transcription by altering the chromatin architecture. HMGA2 was found overexpressed in a variety of epithelial and mesenchymal tumors and promoted invasion and metastasis in most malignant epithelial tumors. A recent study showed that P53 inhibited CRC progression by targeting HMGA2. However, the mechanism by which HMGA2 affect angiogenesis in CRC has not been clarified. Methods: The expression of HMGA2 was analyzed by IHC, WB and bio infomatic analysis. Cbioportal and mexpress online tools were applied to explore the CNV and methylation of HMGA2 in CRC patients. Single cell data from GEO was used to examine the specific cell type that contribute to the high HMGA2 expression in CRC. Lentivirus was used to knock down HMGA2 in CRC cells and HUVECs was used to study angiogenesis. Results: In the current study, we first detected the expression pattern of HMGA2 in CRC patients and evaluated its clinical values and CNV amplification could possibly contribute to the up regulation of HMGA2 in CRC patients. By analyzing CRC single cell data we found that HMGA2 was specifically up regulated in the colorectal epithelial cells. Furthermore, knocking down of HMGA2 suppresses angiogenesis via dual regulation of VEGF-A and SEMA3A in CRC through inactivating VEGRR2 pathway in HUVECs. Conclusions: HMGA2 might be a promising prognostic marker and target for treating advanced CRC patients.

Background: Intelligence quotient (IQ) is a measure of intellectual ability of performing, comprehension, and learning. Previous studies reported that intelligence measures predict various measures of job performance and income. Emotional awareness (EA) is the measure of emotional capacity to recognize and make sense of one’s emotions, as well as those of others. A high level of emotional awareness (EA) indicates one can learn from expressed emotions quickly. Both IQ and EA are important for personal and professional success.Objective: This study tests the hypothesis that the average national income rank is best predicted by the combined effect of the population's average intelligence quotient (one's ability to perform and learn) and emotional awareness (ability to recognize and make sense of emotions).Method: The population’s average intelligence quotient (IQ), emotional awareness (EA), and indices of good governance, which include corruption perception index and educational expenses for each country, were obtained from public data sources. The outcome variable was per capita gross national income. All the variables that are statistically significant in univariate analysis were included in the multivariate regression analyses but excluded from the final model if not statistically significant.Result: The total number of countries included in the final analysis was 81 because of missing values in different variables. Intelligence quotient (IQ) and emotional awareness (EA) were found to be highly correlated, at 0.77 and 0.32 respectively, with the per capita gross national income. The independent effects of intelligence quotient (IQ) and emotional awareness (EA) were found significant in the multivariate model after adjusting for measures of good governance. The R square value for the final multivariate model was 0.82. The corruption perception index (CPI) and educational expenses were strongly correlated with other measures of good governance such as democracy index, functioning of government, electoral process and pluralism, political participation, and civil liberty, but these variables were found not significant in the multivariate model. Conclusion: The study concludes the effect of intelligence quotient (IQ) and emotional awareness (EA) are complementary to each other but intelligence quotient (IQ) is a stronger predictor than emotional awareness (EA) for gross national income or wealth. We also find that indicators of good governance, including corruption perception index and educational expenses, have important associations with per capita gross national income. This study implies a nation may build more wealth if the educational system focuses on developing emotional awareness in addition to intelligence. The study concludes the effect of intelligence quotient (IQ) and emotional awareness (EA) are complementary to each other but intelligence quotient (IQ) is a stronger predictor than emotional awareness (EA) for gross national income or wealth. We also find that indicators of good governance, including corruption perception index and educational expenses, have important associations with per capita gross national income. This study implies a nation may build more wealth if the educational system focuses on developing emotional awareness in addition to intelligence.

For the majority of the contractual arrangements used in construction projects, the owner is not responsible for the cost deviations due to the variability of labor productivity or material price, amongst many other aspects. Consequently, the cost performance of a project may be entirely distinct for the owner and the contractor. Since the majority of the quantitative research on cost estimation and deviation found in the literature adopts the owners’ perspective, this research provides a contribution towards modelling costs and cost deviation from a contractors’ perspective. From an initial sample of 13 residential building and 10 office building projects, it was possible to develop models for cost estimation at the early stage of development including both endogenous and exogenous variables. Although the sample is relatively small, the authors were able to fully analyze all the cost data, using no secondary sources of data (very frequent in cost modelling studies). The statistically significant variables in the cost estimation models were the areas above and below ground and the years following the 2008 financial crisis, including the international bailout (2011-2014) period. For estimating the unit cost, a nonlinear model was obtained with the number of underground and total floor, the floor ratio and the years following the 2008 financial crisis, including the international bailout (2011-2014) period as predictors. For the office buildings, it was also found a statistically significant correlation between the cost deviation and the number of underground floors.

Epigenetic mechanisms, including post-translational modifications of DNA and histones that influence chromatin structure, regulate gene expression during normal development, and are also involved in carcinogenesis and cancer progression. The histone methyltransferase G9a (euchromatic histone lysine methyltransferase 2, EHMT2), which mostly mediates mono- and dimethylation by histone H3 lysine 9 (H3K9), influences gene expression involved in embryonic development and tissue differentiation. Overexpression of G9a has been observed in several cancer types, and different classes of G9a inhibitors have been developed as potential anticancer agents. Here, we review the emerging evidence suggesting the involvement of changes in G9a activity in brain tumors, namely glioblastoma (GBM), the main type of primary malignant brain cancer in adults, and medulloblastoma (MB), the most common type of malignant brain cancer in children. We also discuss the role of G9a in neuroblastoma (NB) and the drug development of G9a inhibitors.

Pulmonary fibrosis causes scar tissue formation that disrupts the functioning of the lungs. Uncaria gambir (Hunter) Roxb (hereafter gambir)—a plant native to West Sumatra in Indonesia—contains flavonoid (+)-catechin and has strong antioxidant activity, and it can be used to combat pulmonary fibrosis. This random in vivo experimental study analyzed the antifibrotic effect of gambir on the lungs of rats with bleomycin-induced fibrosis. The subjects were 10 groups of 10-week-old male rats weighing around 200–250 g. All groups were terminated at the end of the seventh week or on day 50. The lungs were cleaned, and tissues were taken to analyze inflammatory cell counts and TGF-β1 levels using bronchoalveolar lavage (BAL) with ELISA; type I collagen and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels using immunohistochemistry (IHC); and activation of NF-κB using ELISA and Western blot assays. The most severe histopathological characteristic based on the modified Ashcroft score was in the bleomycin group (BG), whereas the mildest was in the 262 mg/kg of bodyweight antifibrotic gambir-dosed group (AF G262). The results showed a significant difference in the BAL inflammatory cell count (p = 0.017; p < 0.05). AF G262 differed most from the other antifibrotic groups in terms of the number of inflammatory cells (0.63), TGF-β1 levels (3.80), and NF-κB levels (0.48), followed by the 131 mg/kg of bodyweight antifibrotic gambir-dosed group (AF G131), which also differed most from other antifibrotic groups in terms of NF-κB (0.48), TIMP-1 (11.74), and collagen I (14.50) levels. Western blot analysis showed that the fibropreventive and antifibrotic groups had a specific band size of p65, whereas no specific band binding existed in the control group. This study concluded that the administration of AF G262 could improve fibrosis by lysing the extracellular matrix (ECM) in rat lungs.

This paper seeks to optimize the mechanical and durability properties of ultra-high performance concrete (UHPC). To meet this objective, concrete specimens were manufactured by using 1,100 kg/m3 of binder, water/binder ratio 0.20, silica sand and last generation of superplasticizer. Silica fume, metakaolin and two types of nano silica were used for improving the performances of the concrete. Additional mixtures included 13mm long OL steel fibers. Compressive strength, electrical resistivity, mercury intrusion porosimetry tests and differential and thermogravimetric thermal analysis were carried out. The binary combination of nano silica and metakaolin, and the ternary combination of nano silica with metakaolin and silica fume, led to the best performances of the UHPC, both mechanical and durable performances.

Abstract: Calcium-based catalysts are of a high interest for glycerol polymerization due to their high catalytic activity and large availability. However, their poor stability under reaction conditions is an issue. In the present study, we investigated the stability and catalytic activity of Ca-hydroxyapatites (HAps) as one of the most abundant Ca-source in nature. A stochiometric, a Ca-deficient and a Ca-rich HAps have been synthetized and tested as catalysts in the glycerol polymerization reaction. Deficient and stochiometric HAps exhibited a remarkable 100% selectivity to triglycerol at 15 % of glycerol conversion at 245 °C after 8 h of reaction in the presence 0.5 mol.% of catalyst. Moreover, under the same reaction conditions, Ca-rich HAp showed a high selectivity (88 %) to di- and triglycerol at a glycerol conversion of 27 %. Most importantly, these catalysts were unexpectedly stable towards leaching under the reaction conditions based on the ICP-OES results. However, based on the catalytic tests and characterization analysis performed by XRD, XPS, IR, TGA-DSC and ICP-OES, we found that HAps can be deactivated by the presence of the reaction products themselves, i.e., water and polymers.

For personalized recommender systems,matrix factorization and its variants have become mainstream in collaborative filtering.However,the dot product in matrix factorization does not satisfy the triangle inequality and therefore fails to capture fine-grained information. Metric learning-based models have been shown to be better at capturing fine-grained information than matrix factorization. Nevertheless,most of these models only focus on rating data and social information, which are not sufficient for dealing with the challenges of data sparsity. In this paper,we propose a metric learning-based social recommendation model called SRMC.SRMC exploits users' co-occurrence pattern to discover their potentially similar or dissimilar users with symmetric relationships and change their relative positions to achieve better recommendations.Experiments on three public datasets show that our model is more effective than the compared models.

This review article seeks to provide relevant information about the applicability of cell-based assays in assessing cytotoxicity of phytochemicals in light of several traditional methods available. Phenolic compounds and other phytochemicals are significant resources for drug discovery and development, thus underlining the enormous potentials of plant-derived natural products for the prevention and management of oxidative stress associated with cancer and other diseases. These effects have been linked to the content of phytochemicals such as phenolic compounds and their antioxidant properties. The abundance and complexity of these bio-constituents highlight the need for well-defined methods for the in vitro characterization and quantification of extracts and/or preparations that can translate to in vivo effects. Cell culture systems provide a useful model for basic research and a wide range of clinical in vitro studies and physiological processes as well as assessing the toxicity and therapeutic potential of compounds including plant extracts with potential medicinal benefits. Their use in cancer research provide a useful insight into possible therapeutic properties of phytochemicals at the cellular level. This approach has been instrumental in the initial stages of developing chemotherapeutic agents where human cancer cell lines are used as experimental models. These models have continued to contribute to elucidating specific requirements for certain biochemical events associated with proliferation, metabolism, loss of cell viability/apoptosis. Cell culture systems remain a promising tool in natural product development.

Three-Dimensional mesoporous TiO2 scaffolds of anatase phase possess inherent eximious optical behavior that are beneficial in designing photoelectrodes for solar energy conversion applications. However, substantial efforts have been devoted in maximizing the UV and/or visible light absorption efficiency, and suppressing the annihilation of photogenerated charged species in pristine mesoporous TiO2 structure for improved solar illumination conversion efficiencies. This study provides the fundamental insights into Mxene functionalized mesoporous TiO2 as photoelectrode for the first time. This novel combination of Mxene functionalized TiO2 electrodes with and without TiCl4 treatments have been successfully optimized to intensify the process of photon absorption, charge segregation and photocurrent, resulting in superior photoelectrode performance. The photocurrent measurements of prepared photoelectrodes are significantly enhanced upon increased contents of Mxene due to improved absorption efficiency within the visible region as verified by UV–Vis absorption spectroscopy. Moreover, as evident through structural analysis, the anatase phase of TiO2 is well grown due to increased contents of Mxene and post-deposition heat treatments. Consequently, an appreciable coverage of well-developed grains on FTO surface observed in SEM images. Thereby, the newly fabricated conductive mesoporous TiO2 photoelectrodes are potential candidates for photoinduced energy conversion and storage purposes.

The aim of this study as to determine the relationship between the factors of demography, comor-bidity, medication, lifestyle, and access to health services related to the QoL of people with hy-pertension and its complications in Sleman Regency, Yogyakarta. The study was conducted in a cross-sectional manner using data from Sleman HDSS (Health and Demographic Surveillance System) from 2015 to 2018 in cycles 3 and 2 with the inclusion criteria of hypertensive patients and their complications aged 25 years or older obtained by using a total sampling of 532 people. Measurement of QoL using Short Form 12v2 2a and 2b questionnaires presented in the Physical Component Summary (PCS) and Mental Component Summary (MCS). Data analysis using Mann-Whitney test and Kruskal Wallis test. The results showed factors related to the QoL in PCS were variables of gender, age, diagnosis of hypertension and its complications, the presence of comorbidities, fatty foods, drug consumption in the last two weeks, while factors related to the mental component (MCS) were education and occupation seen from the p-value <0.05. QoL with hypertension and its complications influence and decrease the physical than the patient's mental condition.

Zero-rate output (ZRO) drift induces deteriorated micro-electromechanical system (MEMS) gy-roscope performances, severely limiting its practical applications. Hence, it is vital to explore an effective method toward ZRO drift reduction. In this work, we conduct an elaborate investigation on the impacts of the internal and packaging stresses on the ZRO drift at the thermal start-up stage, and propose a temperature-induced stress release method to reduce the duration and magnitude of ZRO drift. Self-developed high-Q dual mass tuning fork gyroscopes (TFGs) are adopted to study the correlations between temperature, frequency and ZRO drift. Furthermore, a rigorous finite element simulation model is built based on the actual device and packaging structure, revealing the temperature and stresses distribution inside TFGs. Meanwhile, the relationship between temperature and stresses are deeply explored. Moreover, we introduce a temperature-induced stress release process to generate thermal stresses and reduce the temperature-related device sensitivity. By this way, the ZRO drift duration is drastically reduced from ~2000 s to ~890 s, and the drift magnitude decreases from ~0.4 °/s to ~0.23 °/s. This stress release method achieves a small bias instability (BI) of 7.903 °/h and a low angle random walk (ARW) of 0.792 °/√h, and the long-term bias performance is significantly improved.

There has been a steady rise in the recognition of menstrual hygiene management (MHM) as a pressing public health issue due to several advocacy campaigns against its high cost. However, not much of such recognition has been given to it outside the non-profit sector in Nigeria. This is paradoxical considering that most menstruators in Nigeria cannot afford MHM whose cost is considered high even in developed countries. We estimated that the average lifetime cost of MHM in Nigeria is US$1,122.3 per menstruator and US$113.58 billion for the entire menstruating population. Although this cost is relatively lower than in other countries, Nigeria’s low-income level explains why there is a high prevalence of period poverty among menstruators in Nigeria. This commentary highlights the intersected impacts of the cost of MHM and period poverty on the average Nigerian menstruator, his/her family, the economy, the environment and the United Nations Sustainable Development Goals. To alleviate the discussed negative effects, we suggested, as a key recommendation, the national shift from the use of disposable MHM products to that of reusable ones.

Abstract: The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the presence of poly-PR/GR dipeptide repeats which are encoded by the C9orf72 gene. Recently, it was shown that poly-PR/GR alters chromatin accessibility which results in stabilization and enhancement of transcriptional activity of the tumor suppressor p53 in several neurodegenerative disease models. Reduction of p53 protein levels in cell and model organisms protects against neurotoxicity of poly-PR, and partially protects against neurotoxicity of poly-GR. Here, we aimed to study the detailed molecular mechanisms how p53 contributes to poly-PR/GR mediated neurodegeneration. Using a combination of biophysical techniques such as nuclear magnetic resonance (NMR) spectroscopy, fluorescence polarization, turbidity assays and differential interference contrast (DIC) microscopy, we found that p53 physically interacts with poly-PR/GR and triggers liquid-liquid phase separation of p53. We identified p53 transactivation domain 2 (TAD2) as the main binding site for PR25/GR25 and show that binding of poly-PR/GR to p53 is mediated by a network of electrostatic and/or hydrophobic interactions. Our findings might help to understand the mechanistic role of p53 in poly-PR/GR - associated neurodegeneration.

Since its advent in the mid-twentieth century, the field of artificial intelligence (AI) has been heavily influenced by biology. From the structure of the brain to evolution by natural selection, core biological concepts underpin many of the fundamental breakthroughs in modern AI. Here, focusing specifically on artificial neural networks (ANNs) that have become commonplace in machine learning, we show the numerous connections between theories based on coevolution, multi-level selection, modularity and competition and related developments in ANNs. Our aim is to illuminate the valuable but often overlooked inspiration biologists have provided AI research and to spark future contributions at this intersection of biology and computer science. Although recent advances in AI have been swift, many significant challenges remain requiring innovative solutions. Thankfully, biology in all its forms still has a lot to teach us, especially when trying to create truly intelligent machines.

Facing unprecedented global declines in the extent and integrity of ecosystems, the 15^th UN Biodiversity Conference (COP-15) in Kunming, China, presents an opportunity for transformative change. However, a lack of consensus on two key issues – resource mobilization and Access and Benefit Sharing (ABS) associated with Digital Sequence Information (DSI) – risks stalling negotiations for an ambitious ‘Post-2020 Global Biodiversity Framework’ as the next 10-year strategic plan under the Convention on Biological Diversity. We highlight systemic misconceptions concerning the financing of biodiversity and the burden this places on the ABS system. In the context of DSI, we caution that conflating ABS with resource mobilization risks disrupting modern science policy built on open access, with potentially severe ramifications for scientific research and innovation. To resolve these tensions, we call for a recalibration of discussions on ABS in order to maximize the value delivered by biodiversity for all of society, including indigenous peoples and local communities.

The research is based on the question: Can teaching/learning methodologies help to achieve the objective of Sumak Kawsay in Ecuador? a STEAM work approach was applied in technical high school students and higher education students (technological), in order to determine the level of impact in terms of project generation, following the entire process, from the generation of ideas to the linking of projects with society, The analysis was carried out in students from 15 to 22 years old in two institutions in the city of Cuenca, using the method of intentional sampling and the systematic review of scientific articles in the Scopus and Google academic databases of the last 3 years, to determine the level of impact of the prototypes pub-lished in indexed journals. The most striking aspect of the results is that of the 260 students surveyed, only 19.6% of students consider that there are STEAM teachers in the classroom, and only 56.92% of students manage to link their work with society, one of the recommended strategies being the publication of scientific articles and participation in congresses disseminating the high impact work done by students in the classroom.

We investigated the role of the human medio-temporal complex (hMT+) in the memory encoding and storage of a sequence of four coherently moving RDKs by applying repetitive transcranial magnetic stimulation (rTMS) during an early or late phase of the retention interval. Moreover, in a second experiment we also tested whether disrupting the functional integrity of hMT+ during the early phase impaired the precision of the encoded motion directions. Overall, results showed that both recognition accuracy and precision were worse in middle serial positions, suggesting the occurrence of primacy and recency effects. We found that rTMS delivered during the early (but not the late) phase of the retention interval was able to impair not only recognition of RDKs, but also the precision of the retained motion direction. However, such impairment occurred only for RDKs presented in middle positions along the presented sequence, where performance was already closer to chance level. Altogether these findings suggest an involvement of hMT+ in the memory encoding of visual motion direction. Given that both position sequence and rTMS modulated not only recognition but also precision of the stored information, these findings are in support of a model of visual short-term memory with a variable resolution of each stored item, consistent with the assigned amount of memory resources, and that such item-specific memory resolution is supported by the functional integrity of area hMT+.

Cyanobacteria are microorganisms able to adapt to a wide variety of environmental conditions and abiotic stresses. They produce a very large number of metabolites that can participate in the adaptation of cyanobacteria to a large range of resources such as light, temperature, or nutrient. The metabolites variation is one way to understand the physiological status and adaptation of cells. In this study, we aim to understand how the diversity and the dynamics of the whole metabolome is dependent of the growth phases and under control of abiotic factors (e.g. light intensity and temperature). The cyanobacteria Aliinostoc sp. PMC 882.14 was selected for its large number of biosynthetic gene clusters. Metabolomes were analyzed by using mass spectrometry (qTOF-MS/MS) combined with untargeted analysis to investigate the metabolite dynamics. Significant variations were characterized between exponential and stationary phases, whatever the culture conditions (“control”, “higher light”, or “higher temperature”). ”Higher light” and “higher temperature” favored the synthesis of metabolites belonging to the same molecular families. Among highly regulated metabolites, we observe the presence of mycosporine-like amino acids (MAAs), and various variants of somamides, microginins, and microviridins. Through Aliinostoc sp. PMC 882.14, this study shows the importance of knowing the physiological state of cyanobacteria for comparative global metabolomics and questions the regulation processes involve into metabolite families production. Our results also open up new perspectives in the context of the production of targeted bioactive metabolites.

It is shown how the secondary structure of proteins, musical forms and verses of poems are approximately ruled by universal laws relying on graph coverings. In this direction, one explores the group structure of a variant of the SARS-Cov-2 spike protein and the group structure of apolipoprotein-H, passing from the primary code with amino acids to the secondary structures organizing the foldings. Then one look at the musical forms employed in the classical and contemporary periods. Finally, one investigates in much detail the group structure of a small poem in prose by Charles Baudelaire and that of the Bateau Ivre by Arthur Rimbaud.

This paper consists of two parts. In part I some new relations for a field theory with time intervals are derived. One concept of field theory evaluated is complementarity, another is field operators both defined within a time interval description. Part II includes specific results and commentary. Discussed are time interval dependent wave propagation surfaces for star source emission waves and derived is a metric propagation surface area requirement. The results allow to consider one same field that like gravitation within General Relativity applies to both non zero and zero mass. The associated field energy is space time dependent for non zero mass, and is related to a space time dependent metric tensor for zero mass wave particles. Defined is internal energy transfer where wave particle numbers increase linearly and mass and momentum diminish, decrease inversely with the distance from the wave emission source. The commentary are applications related to cosmological overall volume and temperature dependence.

Dengue is the most prevalent arthropod-borne disease globally and affects approximately 2.5 billion people living in over 100 countries. The increasing geographic expansion of Aedes aegypti mosquitoes which transmit the virus has made dengue fever a global health concern. There are currently no approved antivirals available to treat dengue, and the only approved vaccine used in some countries is limited to seropositive patients. Treatment of dengue therefore remains largely supportive to date; hence research efforts are being intensified for the development of antivirals against dengue. The NS3 and NS5 nonstructural proteins have been the major targets for dengue antiviral development due to their indispensable enzymatic and biological functions in the viral replication process. NS5 is the largest and most conserved nonstructural protein encoded by flaviviruses including dengue. Its multifunctionality makes it an attractive target for antiviral development against dengue, but research efforts are hindered due to its limited structural characterization compared to the NS5 of other flaviviruses like the Zika virus. Increase in structural insights into the dengue NS5 protein will accelerate drug discovery efforts focused on NS5 as an antiviral target. In this review, we will give an overview of the current state of therapeutic development against dengue.

An effective battery management system (BMS) is indispensable for any lithium-ion battery (LIB) powered systems such as electric vehicles (EVs) and stationary grid-tied energy storage systems. Massive wire harness, scalability issue, physical failure of wiring, and high implementation cost and weight are some of the major issues in conventional wired-BMS. One of the promising solutions researchers have come up with is the wireless BMS (WBMS) architecture. Despite research and development on WBMS got momentum more than a decade ago, it is still in a preliminary stage. Significant further upgradation is still required towards developing an industry-ready WBMS, especially for high-power LIB packs. Therefore, an in-depth survey exclusively on WBMS architectures is presented in this article. The aim is to provide a summary of the existing developments as well as to present an informative guide to the research community for future development by highlighting the issues, emerging trends, and challenges. In-depth analysis of the existing WBMS topologies will not only help the researchers to understand the existing challenges and future research scopes clearly while at the same time enthuse them to focus their research inclination in the domain of WBMS.

Methotrexate (MTX) is a potent drug for the treatment of various diseases globally amidst being a chemotherapeutic and immunosuppressant agent. However, hepatotoxicity induced by MTX could be life-threatening if left untreated. Folate supplementation is concurrently applied to reduce the adverse effects of MTX, albeit efficacy compromise. Therefore, there is the need to understand the process for the prevention and treatment strategies for MTX induced hepatotoxicity (MIH). In recent times, preliminary preclinical and clinical findings indicate the potential of natural phytobioactive compounds for MIH prevention and treatment. This mini review therefore summarizes proposed mechanisms of MIH and recent advances in the prevention and treatment prospects of natural phytobioactive compounds on MIH.

A position sensing glove, called SmartScan, that creates a 3D virtual model of a real object is presented. The data from the glove is processed by a volume minimization algorithm to validate the position sensor data. This allows only data from the object’s surface to be retained. The data validation algorithm allows the user to progressively improve an image by repeatedly moving their hand over the object. In addition, the user can choose their own balance between feature resolution and invalid data rejection. The SmartScan glove is tested on a foot model and is shown to be robust against motion artifacts, and has a mean accuracy of 2.9 mm (compared to a 3D model generated from optical imaging) without calibration.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman’s correlation and Kapan Meier tests were conducted for correlation and survival analyses respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose, lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used in predicting patient survival and in informing treatment intervention.

This paper reports applying Minimax principle and impulsive differential inequality to derive the existence of multiple stationary solutions and the global stability of a positive stationary solution for a delayed feedback Gilpin-Ayala competition model with impulsive disturbance. The conclusion obtained in this paper reduces the conservatism of the algorithm compared with the known literature, for the impulsive disturbance is not limited to impulsive control.

Functional osseoconductive coatings based on hydroxylapatite (HAp) and applied preferentially by atmospheric plasma spraying to medical implant surfaces are a mainstay of modern implantology. During contact with the hot plasma jet, HAp particles melt incongruently and undergo complex dehydration and decomposition reactions that alter their phase composition and crystallographic symmetry, and thus, the physical and biological properties of the coatings. Surface analytical methods such as laser-Raman and nuclear magnetic resonance (NMR) spectroscopies are useful tools to assess the structural changes of HAp imposed by heat treatment during their flight along the hot plasma jet. In this contribution, the controversial information on the existence or non-existence of oxyapatite, i.e. fully dehydrated HAp as a thermodynamically stable compound is highlighted.

Deep learning (DL), a branch of machine learning (ML) and artificial intelligence (AI) is nowadays considered as a core technology of today's Fourth Industrial Revolution (4IR or Industry 4.0). Due to its learning capabilities from data, DL technology originated from artificial neural network (ANN), has become a hot topic in the context of computing, and is widely applied in various application areas like healthcare, visual recognition, cybersecurity, and many more. However, building an appropriate DL model is a challenging task, due to the dynamic nature and variations in real-world problems and data. Moreover, the lack of core understanding turns DL methods into black-box machines that hamper development at the standard level. This article presents a structured and comprehensive view on DL techniques including a taxonomy considering various types of real-world tasks like supervised or unsupervised. In our taxonomy, we take into account deep networks for supervised or discriminative learning, unsupervised or generative learning as well as hybrid learning and relevant others. We also summarize real-world application areas where deep learning techniques can be used. Finally, we point out ten potential aspects for future generation DL modeling with research directions. Overall, this article aims to draw a big picture on DL modeling that can be used as a reference guide for both academia and industry professionals.

In humankind’s endeavor to explore beyond our planet and travel further into space, we are now at the threshold of an era in which it is possible to move to and from low Earth orbit (LEO) with increasing ease and reduced cost. Through the International Space Station (ISS) U.S. National Laboratory, investigators from industry, academia, and government can easily access the unique LEO environment on the ISS to conduct research and development (R&D) activities in ways not possible on Earth. A key advantage of the LEO environment for life sciences research is the ability to conduct experiments in sustained microgravity conditions. The ability to conduct long-term research in microgravity enables opportunities for novel, fundamental studies in tissue engineering and regenerative medicine, including research on stem cell proliferation and differentiation, biofabrication, and disease modeling using microphysiological systems (MPS) that build on prior research using simulated microgravity conditions (Grimm, D., et al. 2018). Over the last decade, space-based research has demonstrated that microgravity informs our knowledge of fundamental biology and accelerates advancements in health care and medical technologies (International Space Station 2019). The benefits provided by conducting biomedical research in LEO may lead to breakthroughs not achievable on Earth. We are now at a transition point, in which nations are changing their approach to space-based R&D. The focus is shifting from government-funded fundamental science toward the expansion of privately funded R&D with terrestrial application and economic value that will drive a robust marketplace for innovation and manufacturing in LEO. Making this long-term transition requires public-private participation and near-term funding to support critical R&D to leverage the benefits of the LEO environment and de-risk space-based research. Studies conducted on the ISS over the past several years have indicated that one area with potential significant economic value and benefit to life on Earth is space-based biomanufacturing, or the use of biological and nonbiological materials to produce commercially relevant biomolecules and biomaterials for use in preclinical, clinical, and therapeutic applications. We must take advantage of the remaining lifetime of the ISS as a valuable LEO platform to demonstrate this economic value and Earth benefit. By facilitating access to the space station, the ISS National Lab is uniquely positioned to enable the R&D necessary to bridge the gap between the initial discovery phase of space-based biomedical research and the development of a sustainable, investment-worthy biomanufacturing market in LEO supported by future commercial platforms. Through a joint effort, the Center for the Advancement of Science in Space (CASIS), which manages the ISS National Lab, and the University of Pittsburgh’s McGowan Institute for Regenerative Medicine brought together thought leaders from around the U.S. for a Biomanufacturing in Space Symposium that consisted of a series of working sessions to review data from past space-based tissue engineering and regenerative medicine research, discuss relevant current space-based R&D in this area, and consider potential future markets to address the questions: What are the most promising opportunities to leverage the ISS to advance space-based biomanufacturing moving forward? What are the current gaps or barriers that, if overcome, could clear pathways toward private investment in LEO as a valued site for research, development, and production activity? And, most importantly: For which opportunities do the most compelling value propositions exist? The goal of the Biomanufacturing in Space Symposium was to help identify the specific areas in which government and industry investment would be most likely to stimulate advancements that overcome barriers. This would lead to a more investment-ready landscape for private interests to enter the market and fuel exponential growth. The symposium was meant to serve as the first step in developing a roadmap to a sustainable market for biomanufacturing in space. The symposium identified and prioritized multiple key R&D opportunities to advance space-based biomanufacturing. These opportunities fall in the areas of disease modeling, stem cells and stem-cell-derived products, and biofabrication. Additionally, symposium participants highlighted the critical need for additional data to help validate and de-risk these opportunities and concluded that approaches such as automation, artificial intelligence (AI), and machine learning will be needed to produce and capture the required data. Symposium participants also came to a consensus that public-private partnerships and funding will be needed to advance the opportunities toward a biomanufacturing marketplace in LEO. This paper will summarize the current state of the science and technology on the ISS and in the fields of tissue engineering and regenerative medicine; provide an overview of biomanufacturing R&D in space to date; review the goals of the Biomanufacturing in Space Symposium; highlight the key commercial opportunities and gaps identified during the symposium; provide information on potential market sizes; and briefly discuss the next steps in developing a roadmap to biomanufacturing in space.

Choline kinase inhibitors are an important class of cytotoxic compounds useful for the treatment of different forms of cancer since aberrant choline metabolism is a feature of neoplastic cells. Here we present the characterization and the structure activity relationship of a series of non-symmetrical choline kinase inhibitors characterized by a 3-aminophenol moiety, bound to 4-(dimethylamino)- or 4-(pyrrolidin-1-yl)pyridinium cationic heads through several linkers. These derivatives were evaluated both for their inhibitory activity on the enzyme and for their antiproliferative activity in a panel of six human tumor cell lines. The compounds with the best inhibitory results were those connected to the linker by the N-atom (4a-h) and these results are supported by docking studies. The compounds with the best antiproliferative results were those connected to the linker by the O-atom (3a-h). On the other hand, as was predictable in both families, the inhibitory effect on the enzyme is greater the shorter the length of the linker, while in tumor cells, lipophilicity and choline uptake inhibition could play a decisive role. Interestingly compounds 3c and 4f, selected for both their ability to inhibit the enzyme and good antiproliferative activity, are endowed with a low toxicity in non-tumoral cells (e.g human peripheral lymphocytes) respect to cancer cells. These compounds were also able to induce to induce apoptosis in Jurkat leukemic cells without causing significative variations of cell cycle. It is worth to mention that these derivatives, beside their inhibitory effect on choline kinase, displayed a modest ability to inhibit choline uptake thus suggesting that this mechanism may also contribute to the observed cytotoxicity.

Background: In an age where information is generally accessible, most of the interest these days has focused on how accessible and convenient technology can be. So small and personal, mobile devices can transform our perception of learning by combining both mobility and convenience. Mobile learning is part of the digital learning landscape alongside e-learning and serious games. However, knowledge about effective design of mobile learning experiences remains of interest with a focus on appropriate design models and the embodiments that can be implemented to achieve the intended educational outcomes. Exploring the instructor's perspective on mobile learning is essential. Therefore, the aim of this study was to investigate the Moroccan instructors' perception and practice of mobile learning to inform the development of an ecologically valid mobile learning integration model. Methods: Higher education Instructors (n=41) were recruited to the study. The Moroccan instructors' perception and their experiences regarding their adoption of mobile learning were collected using an online survey. The analysis focused on their mobile use, perceived IT competency, and opinions on mobile learning. Results: We described most of the instructors' considerations regarding integrating mobile technologies into their teaching activities. We found that most of the mobile learning activities defined by the respondents corresponded to relatively advanced use of mobile devices. More promising, instructors have found innovative ways to use the educational potential of mobile devices. However, the prospect of mobile devices was still to challenge. No or poor Wi-Fi connection, number of devices or limited access, sometimes fees or applications incompatibility were identified as reasons and obstacles to mobile learning usage. Conclusion: Mobile learning is mostly perceived positively among Moroccan instructors allowing many applications and usage to enhance teaching and learning. In this study, a better understanding of aspects and factors influencing the integration of mobile learning in the Moroccan educational context is exposed, helping further the development of an ecologically valid mobile learning integration model. Future work on mobile learning should consider the highly paced evolution of mobile technologies, emphasizing the flexibility of integration frameworks to support instructors and learners.

Background: Serious games are conceptualized as a broad topic and overlap segments of more modern forms of education: e-learning, edutainment, game-based learning, and digital game-based learning. Serious Games aligns with digitalization and the modern era and creates novel opportunities for learning and assessment in medical education. Escape rooms, a type of serious games, merge mental and physical aspects to reinforce critical skills useful in daily life. It challenges logic and reasoning and demands careful analysis of situations to correlate and solve different stages of the escape room under pressurized, timed conditions. Furthermore, it serves as an adequate environment to build problem-solving skills, communication skills, and leadership skills through the collaboration of people to achieve a common goal. The aim of this study was to investigate the applications of escape rooms in Medical Education. Method: This study investigated the applications of escape rooms in medical education. Serious games are expanding in education and have attained great relevance due to their intriguing and intrinsically motivating attributes. Within serious games, we focused on escape rooms in which participants are locked in a room, faced with puzzles that must be solved to ‘escape the room’. Compiling the data from the first 100 hits of medical application of escape rooms, we found 72 cases and categorized them by year, specialty, participants structure, simulation experience, and design. Results: We reported on escape rooms in medical education by the year in which they were reported, the medical specialty, the participant structure, grouped or individual, the experience design; real, hybrid, or digital, and the modality of the delivery. 72% of the escape rooms focused on four main areas: nursing education (25.0%), emergency medicine (22.2%), pharmacy (12.5%), and interprofessional education (12.5%). Most of the escape rooms had a group-based physical design and little attention was given to provide a detailed description of the design considerations, such as the pathway type (linear, semi-linear, open). Conclusion: Escape rooms are applied in a wide range of medical education areas. In Medical Education, group-based on-site escape rooms with a focus on nursing, emergency medicine, pharmacy and interprofessional education dominates the implementation landscape. To further advance the field, stronger emphasis on making explicit the design considerations will advance the research and inform implementations.

Every (multimedia) service needs to be accessible. Accessibility for multimedia content is typically provided by means of access services, of which subtitling is likely the most widespread one. Up to date, many recommendations and solutions for subtitling classical 2D audiovisual services are available. Likewise, recent efforts have been devoted to devising adequate subtitling solutions for VR360 video content. This paper, for the first time, goes a step beyond, by exploring two key requirements to fulfill remaining challenges towards efficiently subtitling 3D Virtual Reality (VR) content: presentation modes, and guiding methods. By leveraging insights from earlier work on VR360 content, the paper proposes novel presentation modes and guiding methods to not only deal with the freedom to explore the omnidirectional scenes, but also with additional specificities of 3D VR compared to VR360 content: depth, 6 Degrees of Freedom (6DoF), and viewing perspectives. The obtained results prove that always-visible and a novel proposed comic-style presentation mode are far more appropriate than state-of-the-art fixed-positioned subtitles, mainly in terms of immersion, ease and comfort of reading, and identification of speakers, when applied to professional pieces of content with limited displacement of speakers and with limited 6DoF (i.e. users are not expected to largely navigate around the virtual environment). Likewise, even in such limited movement scenarios, the results show that the use of indicators (arrows), as guiding methods, is well received. Overall, the paper provides relevant insights and paves the way toward efficiently subtitling 3D VR content.

Growing evidence suggests sleep plays an important role in the development of healthy adolescents, with increased interest in the associations between sleep and mental health. Higher duration and quality of sleep has been suggested as a mechanism for increased wellbeing in adolescents. Cross sectional data was collected from 5,661 Irish adolescents. 55% of Irish adolescents reported meeting the guidelines for adolescents of 8-10 hours per night. This was found to decrease with age. Higher duration and quality of sleep was positively associated with wellbeing and negatively associated with symptoms of anxiety and depression. A higher frequency of physical activity was associated with longer duration and higher quality of sleep. 9-10 hours of sleep was associated with the highest levels of wellbeing and lowest symptoms of anxiety and depression. The relationship between physical activity and increased wellbeing may be impacted by physical activity leading to higher durations and quality of sleep.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the lack of estrogen receptors (ER), progesterone receptors, and HER-2 receptors. Thus, TNBC tumours do not benefit from the current therapies targeting ER or HER-2. Therefore, there is an urgent need to develop novel treatment for this subtype of breast cancer. Marijuana is a common name given to Cannabis plants, a group of plants in the Cannabis genus of the Cannabaceae family. Cannabis plants are among the oldest cultivated crops, traced back at least 12,000 years and are well known for their multi-purpose usage, including medicinal purposes. The main active compounds extracted from Cannabis plants are 21-carbon-containing terpenophenolics, which are referred to as phytocannabinoids. Of these, the tetrahydrocannabinol (THC) group contains highly potent cannabinoids, including delta-9-tetrahydrocannabinol (∆9-THC) and delta-8-tetrahydrocannabinol (∆8-THC), which are the most abundant THCs and are largely responsible for psychological and physiological effects of marijuana. The use of Cannabis plants for medicinal purposes was first recorded in 2337 BC in China, where Cannabis plants were used to treat pains, rheumatism, and gout. Recently, several cannabinoids have been approved for a number of treatments, one of which is the treatment of nausea and vomiting caused by chemotherapy in cancer patients. Furthermore, increasing evidence shows that cannabinoids not only attenuate side effects due to cancer treatment, but might also potentially possess direct antitumor effects in several cancer types, including breast cancer. However, anti-tumour activity of marijuana has been variable in different studies and even promoted tumour growth in some cases. In addition, the mechanisms of cannabinoid action in cancer remain unclear. This review summarizes evidence about the mixed actions of cannabinoids in cancer in general and triple-negative breast cancer in particular.

The aerospace industry develops prognosis and health management algorithms to ensure better safety on board. Particularly for in-flight controls where jamming is dreaded. For that, vibration signals are monitored to predict future defect occurrences. However, time series are not labeled according to severity level, and the user can only assess the system health from the data mining procedure. To that extent, we developed a clustering algorithm using a deep neural network core. We encoded the time series into pictures to be feed into an artificially trained neural network: U-NET. From the segmented output, one-dimensional information on cluster frontiers is extracted and filtered without any parameter selection. Then, a kernel density estimation finally transforms the signal into an empirical density. Ultimately, a Gaussian mixture model extracts the latter independent components. The method empowered us to reveal different degrees of severity faults in the studied data, with their respective likelihood without prior knowledge. We compared it to state-of-the-art machine learning algorithms. However, internal clustering results evaluation for time series is an open question. As state-of-the-art indexes were not producing relevant results, we built a new indicator to fulfill this task. We applied the whole method to an actuator consisting of an induction machine linked to a ball screw. This study lays the groundwork for future training of diagnosis and prognosis structures in the health management framework.

Objective: The combination of docetaxel (DTX) with Laser-Activated NanoTherapy (LANT), as a treatment for head and neck cancer (HNC) may enhance the therapeutic efficacy of lower doses of DTX, thereby minimizing the effective dosage, side effects and treatment times. Material and methods: Three HNSCC cell lines, Detroit 562, FaDu, and CAL 27, were treated with four combinations of DTX + LANT to evaluate DTX dose reduction and cell viability. Results: The 1 nM DTX + 5 nM LANT combination was the most effective treatment, increasing cell death over its corresponding DTX monotreatment with approximately 86.6%, 80.7%, and 92.1% cell death for Detroit 562, FaDu, and CAL 27, respectively. In Detroit 562, the 1 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 84.6%; in FaDu and CAL 27, the 0.5 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 78.2% and 82.4%, respectively. Conclusion: LANT may increase the therapeutic efficacy of DTX at significantly lower doses, which could improve patient outcomes.

Since the 1970s, the application of microprocessor in industrial machinery and the development of computer systems have transformed the manufacturing landscape. The rapid integration and automation of production systems have outpaced the development of suitable human design criteria, creating a deepening gap where human factor was seen as an important source of errors and disruptions. Today the situation seems different: the scientific and public debate about the concept of Industry 4.0 has raised the awareness about the central role humans have to play in manufacturing systems, to the design of which they must be considered from the very beginning. The future of industrial systems, as represented by Industry 4.0, will rely on the convergence of several research fields such as Intelligent Manufacturing Systems (IMS), Cyber-Physical Systems (CPS), Internet of things (IoT), but also socio-technical fields such as social approaches within technical systems. This article deals with different Human dimensions associated with CPS and IoT and focuses on their conceptual evolution of automatization to improve the sociability of such automated production systems and consequently puts again the human in the loop. Hereby, our aim is to take stock of current research trends, and to show the importance of integrating human operators as a part of a socio-technical system based autonomous and intelligent products or resources. As results, different models of sociability as way to integrate human into the broad sense and/or the development of future automated production systems, were identified from the literature and analysed.

The suspended test masses of gravitational-wave (GW) detectors require precise alignment to be able to operate the detector stably and with high sensitivity. This includes the continuous counter-acting of seismic disturbances, which, below a few Hertz, are not sufficiently reduced by the seismic isolation system. The residual angular motion of suspended test masses is further suppressed by the Angular Sensing and Control (ASC) system. However, in doing so, the angular motion can be enhanced by the ASC at higher frequencies where the seismic isolation system is very effective. This has led to sensitivity limitations between about 10 Hz and 25 Hz of the LIGO detectors in past observation runs. The observed ASC noise was larger than simple models predict, which means that more accurate detector models and new simulation tools are required. We present Lightsaber, a new time-domain simulator of the ASC in LIGO. The simulation is a nonlinear simulation of the optomechanical system consisting of the high-power cavity laser beam and the last two stages of suspension in LIGO including the ASC. The main noise inputs are power fluctuations of the laser beam at the input of the arm cavities, read-out noise of sensors used for the ASC, displacement noise from the suspension platforms, and noise introduced by the suspension damping loops. While the plant simulation uses local degrees of freedom of individual suspension systems, the control is applied on a global angular basis, which requires a conversion between the local and global bases for sensing and actuation. Some of the studies that can be done with this simulation concern mis-centering of the beam-spot (BS) position on the test masses, the role of laser power fluctuations for angular dynamics, and the role of the various nonlinear dynamics.

Existing implementations of game design patterns have largely been confined to theoretical or research settings. Weaknesses in these implementations have prevented game design patterns from being properly evaluated as an educational and practical development tool. This paper examines these weaknesses, describes a method of developing and applying patterns that overcome the weaknesses, and evaluates use of the method for game design education and practice. Weaknesses in existing pattern implementations are: omission of design problems, presumption of functional completeness at the level of pattern languages, narrow topical focus, and lack of a concise, repeatable method for pattern production. Several features of the proposed method were specifically built to address these weaknesses, namely the pattern template, the process for connecting patterns into a language and assessing the language’s scope, a rubric for assessing pattern confidence and interconnectivity confidence, and pattern-building exercises. This method was applied in a classroom setting. Results, as assessed by the evaluation of student work, suggest that creating patterns/pattern languages is an effective pedagogical approach. De-signs produced using designer-created patterns closely align with existing design theory and are clearly understood by students. The above results may indicate that the path to gaining wider acceptance of pattern theory as a design framework within game design is not to produce a universal pattern language but to facilitate the creation of case-specific languages, by students and professional designers, that use a shared ontology and thus can be combined easily to solve the diverse sets of problems faced by these groups.

As a hazardous waste, pickling waste liquor must be properly treated. An alternative consists in promoting the formation of ferrous salts from this residue, due to its higher ferrous content. Since FeCl2·4H2O is widely used in several applications, obtaining pure crystals of this material appears to be an interesting prospect. However, this compound has scarcely been investigated. In the present work, FeCl2·4H2O crystals have been obtained from pickling waste liquors. Their structural and morphological characteristics have been investigated by X-ray diffraction, scanning electron microscopy as well as Mössbauer spectroscopy. In addition, the photoluminescence study of the obtained samples was also assessed. It was observed that after some aging time, the obtained crystals change in colour from green to more yellowish. So, the aged sample has also been evaluated, and their structural characteristics are compared with the original crystals. Despite this, the obtained crystals exhibit a FeCl2·4H2O structure, which is not modified with the aging of the sample.

Two histamine receptor subtypes (HR), namely H1R and H4R, as key components, are involved in the transmission of histamine-induced itch. Although exact downstream signaling mechanisms are still elusive, transient receptor potential (TRP) ion channels play important roles in the sensation of histaminergic and non-histaminergic itch. Aim of this study was to investigate the involvement of TRPV1 and TRPA1 channels in the transmission of histaminergic itch. The potential of TRPV1 and TRPA1 inhibitors to modulate H1R- and H4R-induced signal transmission was tested in a scratching assay in mice in vivo and in vitro via Ca2+ imaging of murine sensory dorsal root ganglia (DRG) neurons. The TRPV1 inhibition led to a reduction of H1R- and H4R- induced itch and reduced Ca2+ influx into the neurons. The TRPA1 inhibitor reduced H4R-induced itch and both H1R- and H4R-induced Ca2+ influx. In conclusion, these results indicate that both channels, TRPV1 and TRPA1 are involved in the transmission of histamine-induced pruritus.

We show that an exponential income distribution will emerge spontaneously in a peer-to-peer economic network that shares the publicly available technology. Based on this finding, we identify the exponential income distribution as the benchmark structure of the well-functioning market economy. However, a real market economy may deviate from the well-functioning market economy. We show that the deviation is partly reflected as the invalidity of exponential distribution in describing the super-low income class that involves unemployment. In this regard, we find, theoretically, that the lower-bound u of exponential income distribution has a linear relationship with (per capita) unemployment compensation. In this paper, we test this relationship for the United Kingdom from 2001 to 2015. Our empirical investigation confirms that the income structure of low and middle classes (about 90% of populations) in the United Kingdom exactly obeys exponential distribution, in which the lower-bound u is exactly in line with the evolution of unemployment compensation.

Data independent acquisition - mass spectrometry (DIA-MS) is becoming widely utilised for robust and accurate quantification of samples in quantitative proteomics. Here, we describe the systematic evaluation of the effects of DIA precursor mass range on total protein identification and quantification. We show that a narrow mass range of precursors (~250 m/z) for DIA-MS enables a higher number of protein identifications. Subsequent application of DIA with narrow precursor range (from 400 to 650 m/z) on Arabidopsis sample with spike-in of known proteins identified 34.7% more proteins than in conventional DIA (cDIA) with a wide precursor range of 400-1200 m/z. When combining several DIA-MS analyses with narrow precursor ranges (i.e., 400-650, 650-900 and 900-1200 m/z), we were able to quantify 10,099 protein groups with a median coefficient of variation of <6%. These findings represent a 59.4% increase in the number of proteins quantified than with cDIA analysis. This is particularly important for low abundance proteins, as exemplified by the 6-protein mix spike-in. In cDIA only 5 out of the 6-protein mix were quantified while our approach allowed accurate quantitation of all six proteins.

Modified structure along latent tracks and track formation process have been investigated in poly(allyl diglycol carbonate), PADC, which is well recognized as a sensitive etched track detector. This knowledge is essential to develop novel detectors with improved track registration property. The track structures of protons and heavy ions (He, C, Ne, Ar, Fe, Kr and Xe) have been examined by means of FT-IR spectrometry, covering the stopping power region between 1.2 to 12,000 eV/nm. Through a set of experiments on low-LET radiations – such as gamma ray -, multi-step damage process by electron hits was confirmed in the radiation-sensitive parts of the PADC repeat-unit. From this result, we unveiled for the first-time the layered structure in tracks, in relation with the number of secondary electrons. We also proved that etch pit was formed when at least two repeat-units were destroyed along the track radial direction. To evaluate the number of secondary electrons around tracks, a series of numerical simulations were performed with Geant4-DNA. Therefore, we are proposing new physical criterions to describe the detection thresholds. Futhermore, we propose a present issue of the definition of detection threshold for semi-relativistic C ions. And as a possible chemical criterion, formation density of hydroxyl group is suggested to express the response of PADC.

Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered as expression vector systems for recombinant protein expression and vaccine development. Due to the presence of non-structural genes encoding the replicase complex, a 200,000-fold amplification of viral RNA occurs in the cytoplasm of infected cells providing extreme transgene expression levels, which is why they are named self-replicating RNA viruses. Expression of surface proteins of pathogens causing infectious disease and tumor antigens provide the basis for vaccine development against infectious diseases and cancer. The self-replicating RNA viral vectors can be administered as replicon RNA, recombinant viral particles, or layered DNA/RNA replicons. Self-replicating RNA viral vectors have been applied for vaccine development against influenza virus, HIV, hepatitis B virus, human papilloma virus, Ebola virus and recently coronaviruses, especially SARS-CoV-2 the causative agent of the COVID-19 pandemic. Measles virus and rhabdovirus vector-based SARS-CoV-2 vaccine candidates have been subjected to clinical trials. Moreover, RNA vaccine candidates based on self-amplifying alphaviruses have also been evaluated in clinical settings. Various cancers such as brain, breast, lung, ovarian, prostate cancer and melanoma have also been targeted for vaccine development. Robust immune responses and protection have been demonstrated in animal models. Clinical trials have shown good safety and target-specific immune responses. Ervebo, the VSV-based vaccine against Ebola virus disease has been approved for human use.

Nonsteroidal anti-inflammatory drugs (NSAIDs), which block the activity of cyclooxygenase (COX) isoenzymes and inhibit the synthesis of prostaglandin, have been used for pain relief. We have developed a method to separate a mixture of three NSAIDs, such as aspirin, paracetamol, and naproxen, using reverse-phase high-performance liquid chromatography (RP-HPLC). An isocratic mobile phase consisting of acidic water and acetonitrile was selected to run at a low flow rate, such as 0.8 mL/min. The mixture of three NSAIDs was injected at a low volume into a C18 column that was 150 mm in length and characterized using a UV detector at 230 nm. We identified three peaks in the chromatogram indicating the three compounds. The elution time of the peaks was less than 10 minutes. To identify multiple peaks on the isocratic flow using a short column, further studies are required regarding the proposed method to generate microfluidic devices for nanoLC.

The survival analysis of the Cancer Genome Atlas (TCGA) dataset is a well-known method to discover the gene expression-based prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC). A cutoff point is usually used in survival analysis for the patients' dichotomization in the continuous gene expression. There is some optimization software for cutoff determination. However, the software's predetermined cutoffs are usually set at the median or quantiles of gene expression value to perform the analyses. There are also few clinicopathological features available on their pre-processed data sets. We applied an in-house workflow, including data retrieving and pre-processing, feature selection, sliding-window cutoff selection, Kaplan-Meier survival analysis, and Cox proportional hazard modeling for biomarker discovery. In our approach for the TCGA HNSCC cohort, we scanned human protein-coding genes to find optimal cutoff values. After adjustment with confounders, the clinical tumor stage and the surgical margin involvement are independent risk factors for patients' prognosis. According to the resulting tables with Bonferroni-adjusted P value under the optimal cutoff and the hazard ratio, three biomarker candidates, CAMK2N1, CALML5, and FCGBP, are significantly associated with the patients' overall survival. We validated this discovery by using the other independent HNSCC dataset (GSE65858). Thus, we suggest the transcriptomic analysis could help for biomarker discovery.

In the search for new 2D materials beyond graphene with similar exemplary properties Stanene the new graphene relative was successfully synthesized and characterized in 2016 [14]. This new material which consists of atomically thin tin (Sn) atoms arranged in a hexagonal lattice has shown great promise in gas sensing applications in its pristine, doped and functionalized forms as evidenced by the recent research outputs following its discovery. Researchers have discovered that with its exotic properties it is highly efficient in the detection of the environmentally harmful gases like SO2, NO2, CO2, NH3 and can serve as a multifunctional gas sensor. In this focused and up-to-date review we aim to group the literature on first principles studies of stanene regards to its application for gas sensing and critically examine the success/failures of its multifunctional gas sensing properties as compared to graphene. We systematically present and discusses how structural deformations, defects and doping effect the gas sensing performance. Despite the impressive progress in the field of gas sensing with stanene shown by first principles calculations, many challenges in large scale synthesis, device fabrication and commercialization need to be addressed. The current review can help understand the current status and drawbacks of stanene and identify future directions in this field.

Determining the vibration environment is crucial to analyzing a design of any mechanical system, especially such dynamic systems as sounding rockets. Accuracy of measurement using accelerometers could be improved by application of mechanical vibration filtering and amplifying devices. This work presents a theoretical description of a tunable filter and amplifier. Principle of work is provided as well as results from application of the device on a sounding rocket are provided. It is shown that implementation of such devices allowed for enhancing the accuracy of acceleration measurements. Conclusions on future implementations are also provided.

Introduction:In this study we evaluated the connivance of oxidative and antioxidative parameters in the pathogenesis of spinal cord injury (SCI). Although the etiology and pathogenesis of SCI remain to be fully understood, it has been suggested that reactive oxygen species (ROS) and oxidative stress may play a significant role in the pathophysiology of SCI. Furthermore, there is little information available in scientific literature about oxidative and antioxidative parameters in SCI patients. Methods:Oxidative stress was determined by measuring the levels of Lipid Peroxides (LPO) and Protein carbonyl in plasma and antioxidative parameters like Glutathione Reductase (GR), catalase and Glutathione peroxidase (GPx) in lysate in 40 SCI patients and 40 healthy subjects without SCI. However, pain was measured by McGill pain questionnaire. Results: Concentrations of catalase (p<0.01), GR (p<0.01) and GPx (p<0.01) were significantly lower in patients with SCI than in controls, and levels of oxidative stress parameters, LPO (p<0.01), Protein carbonyl (p<0.01) were significantly higher in patients than in controls. A significant positive correlation was found between LPO and pain score among SCI patients group. Furthermore, a significant positive correlation was also found between Protein carbonyl and pain score among SCI patients group than in control group. Conclusion: The present results indicate that SCI patients are exposed to oxidative stress and this escalated oxidative stress may play a role in the etiopathogenesis of the disease. Moreover, our results also show that increased oxidative stress parameters are more strongly amalgamated with pain in SCI patients.

Life cycle assessment (LCA) is being included formally in EcoDesign regulations. Especially product carbon footprint will be mandatory in Europe. However, life cycle impact assessment including global warming potential (GWP) in LCA is hampered by several challenges. One of these is lack of water vapor characterization indexes for GWP. A life cycle inventory profile for air transport fuel including water vapor emissions is evaluated with state-of-the-art practice, i.e. EF Method and ILCD 2011 Midpoint+ and neglecting water vapors high altitude GWP compared to carbon dioxide. Then the characterization factor in GWP100 for water vapor and alternate normalization for particulates are introduced. The results are compared. The main findings are that the EF method and ILCD both generate rather realistic results for Particulate Matter and Respiratory Inorganics mid-point indicators, respectively, but the amount of premature deaths should be better allocated to different specific emissions, and that water vapor may dominate the GWP100 result over the usual carbon dioxide. LCIA mid-points need measurable and understandable bases. The common knowledge of water vapor’s GWP100 should not be neglected in LCIA for air transport and beyond where relevant.

The knowledge of the optical properties of biological tissues in a wide spectral range is highly important for the development of noninvasive diagnostic or treatment procedures. The absorption coefficient is one of those properties, from which various information about tissue components can be retrieved. Using transmittance and reflectance spectral measurements acquired from ex vivo rabbit brain cortex samples, allowed to calculate its optical properties in the ultraviolet to the near infrared spectral range. Melanin and lipofuscin, the two pigments that are related to the ageing of tissues and cells were identified in the cortex absorption. By subtracting the absorption of these pigments from the absorption of the brain cortex, it was possible to evaluate the true ratios for the DNA/RNA and hemoglobin bands in the cortex – 12.33 fold (at 260 nm), 12.02 fold (at 411 nm) and 4.47 fold (at 555 nm). Due to the fact that the accumulation of melanin and lipofuscin increases with the ageing of the brain tissues and are related to the degeneration of neurons and their death, further studies should be performed to evaluate the evolution of pigment accumulation in the brain to prevent the development of Alzheimer, Parkinson and stroke pathologies in the brain.

Surface activity of humic acid (HA) and its six sub-fractions isolated from forest soil were characterized by surface tension measurements, dynamic light scattering, and laser doppler electrophoresis. The surface tension of HA sub-fractions decreased from 72.4 mN·m-1 to 36.8 mN·m-1 with the increasing concentration from 0 to 20000 mg·L-1. The critical micelle concentration (CMC) of HA and its sub-fractions ranged from 216 to 1024 mg·L-1 with the multiple linear regression equation of CMC = 18896–6.9×C–296×alkyl-C–331×aromatic-C–17019×H/C+4054×HB/HI (p &lt; 0.05). The Z-average particle size ranges from 108.2 nm to 186.9 nm. The maximum particle size was 5000 nm after filtered with a membrane of 0.45 μm, indicating HA and its sub-fractions progressed self-assembly during 2000 mg·L-1, pH = 6.86. The number-base particle size distribution of HA sub-fractions was identified as four peaks by Gaussian model, and the aggregate sizes were mainly in six clusters including 2 ± 1 nm, 5 ± 2 nm, 10 ± 3 nm, 21 ± 8 nm, 40 ± 10 nm, and &gt; 50 nm indicating multiple aggregations of different particle sizes in the HA fractions solution.

It was the aim of this study to provide a more precise timeframe of development of the gonads and genital ducts in the equine fetus around the time of sexual differentiation. This included the identification and localisation of the primordial germ cell population. Equine fetuses between 45 and 60 days of gestation were evaluated using a combination of micro-computed tomography scanning, immunohistochemistry, and multiplex immunofluorescence. Fetal gonads increased in size by 23-fold from 45 to 60 days of gestation, paralleled by a greater increase in metanephros volume. Signs of mesonephros atrophy were detected during this time. Tubular structures of the fetal testes were present from day 50 onwards, whereas cell clusters dominated in the fetal ovary. The genital ducts were well-differentiated and presented a lumen in all samples. No sign of mesonephric or paramesonephric duct degeneration was detected. Expression of AMH was strong in the fetal testes but absent in ovaries. Irrespective of sex, primordial germ cells selectively expressed LIN28. Migration of primordial germ cells from the mesonephros to the gonad was detected at 45 days, but not at 60 days of development. Their number and distribution within the gonad were influenced (p&lt;0.05) by fetal sex. Most primordial germ cells (86.8 ± 3.2% in females and 84.6 ± 4.7% in males) were characterized as pluripotent according to co-localization with CD117. However, only a very small percentage of primordial germ cells was proliferating (7.5 ± 1.7% in females and 3.2 ± 1.2% in males) based on co-localization with Ki67. It can be concluded that gonadal sexual differentiation in the horse occurs asynchronously with regard to sex but already before 45 days of gestation.

The study aimed to evaluate the association between the changes in ventilatory variables (tidal volume (Vt), respiratory rate (RR), and lung ventilation (VE)) and deoxygenation of m.intescostales (∆SmO2-m.intercostales) during a maximal incremental exercise in nineteen male competitive marathon runners. The ventilatory variables and oxygen-consumption (VO2) were recorded breath-by-breath by exhaled gas analysis. A near-infrared spectroscopy device (MOXY) located in the right-hemithorax allowed recording SmO2-m.intercostales. To explore changes in oxygen levels in muscles with high demand during exercise, a second MOXY records SmO2-m.vastus laterallis. The triphasic model of exercise intensity was used for evaluating changes in SmO2 in both muscle groups. We found that ∆SmO2-m.intercostales correlated with VO2-peak (r=0.65; p=0.002) and the increase of VE (r=0.78; p=0.001), RR (r=0.54; p=0.001), but not Vt (p=0.210). The interaction of factors (muscles X exercise-phases) in SmO2 expressed as an arbitrary unit (a.u) was significant (p=0.005). At VT1 were no difference (p=0.177), but SmO2-m.intercostales was higher at VT1 (p&lt;0.001) and VO2-peak (p&lt;0.001). In competitive marathon runners, the m.intercostales deoxygenation during incremental exercise is directly associated with the aerobic capacity and increased lung ventilation and respiratory rate, but not tidal volume. Besides, it shows less deoxygenation than m.vastus laterallis at intensities above the aerobic ventilatory threshold.

According to Swiss-American Doctor of Sciences and Agricultural Engineer Jean-Pierre Jost, "plants communicate with each other by the quality of light emitted by their leaves or by means of stress hormones and other volatile chemicals. They also make use of cocktails of chemicals, pheromones, shape and colors to attract pollinators whereas other signals repel unwanted organisms. Insects are able to decode such messages and respond accordingly. Plants are apparently also communicating by sounds and electric signals." (1) How do plants do these things? Of course, it's easy to imagine it's all purely mechanical. But at the risk of sounding like a mysticism fanatic, I wonder if plants' activities are part of a spectrum of consciousness that pervades the entire universe. This spectrum would result from everything in the universe having the BITS or BInary digiTS of electronics as their ultimate composition. As explained in this hypothesis, something I call vector-tensor-scalar geometry is essential to my hypothesis. VTS geometry produces the particles of chemicals and pheromones, and refers to communication via electric signals when it speaks of electromagnetic-gravitational interaction. There's another consequence if everything in the universe is ultimately composed of electronic BITS and the cosmos is a spectrum of consciousness/artificial intelligence. It's impossible for an absence of consciousness to exist, either after death or before conception.

Rural clean heating project (RCHP) in China aims to increase flexibility in the rural energy system, enhance the integration of renewable energy and distributed generation, and reduce environmental impact. While RCHP-enabling routes have been studied from a technical perspective, the economic, ecological, regulatory, and policy dimensions of RCHP are yet to be analysed in depth, especially in the underdeveloped areas in China. This paper discusses RCHP in rural Gansu in a multi-dimension approach. We firstly focus on the current issues and challenges of RCHP in rural Gansu. Then the RCHP-enabling areas are briefly zoned into six typical regions based on the resource distribution in Gansu Province, and a matching framework of RCHP is recommended. Then we focus on the economics and sustainability of RCHP-enabling technologies. Based on the medium-term assessment of RCHP in the demonstration provinces, various technical schemes and routes are analysed and compared so as to be adopted in rural Gansu. In addition to technical and economic effects of those schemes, the corresponding ecology, policy, finance, and market implications are also concerned. We briefly discuss how the national regulators incentivise the implementation of RCHP in rural Gansu. Major barriers to RCHP are identified as the sustainability of technology, economy, ecology, policy, finance, and market. Subsequently, some policy solutions to overcome these barriers are proposed.

There is consensus over the fact that urban green areas contribute to the quality of life of their inhabitants. So, efficient city management must assess whether the population has access to green areas and their quality in relation to vegetation, facilities or furnishings, for example. Therefore, the objective set is to establish the environmental justice of urban parks in Tarragona (Spain) by developing a Park Quality Index (PQI) and the sociodemographic characteristics (level of studies, Human Development Index [HDI], home sale and rental prices) of the population living within 300 metres of a park. To prepare this, a GIS-integrated Multi-Criteria Evaluation (MCE) has been produced. The results show that the green areas have low accessibility and availability and that most parks obtain an average-low PQI, with the best- valued aspect being the vegetation and the worst the facilities. As for the degree of environmental justice, a casual relationship emerges between the PQI and the indicators used. The average value of the home sale prices is the one that shows the greatest correlation. These results can be used together with participatory procedures as a basis for identifying places with greater inequality, and for selecting the more effective actions that enable increasing environmental justice with respect to green areas.

The human oral microbiome refers to an ecological community of symbiotic and pathogenic microorganisms found in the oral cavity. The oral cavity is a suitable environment that provides various kinds of biological niches such as teeth, tongue, and oral mucosa. The oral cavity is the gateway between the external environment and the human body, maintaining oral homeostasis, protecting the mouth, and preventing disease. On the flip side, the oral microbiome plays an important role in triggering, development, and progression of oral and systemic diseases. Currently, disease diagnosis through the analysis of the human oral microbiome has been realized with the recent development of innovative detection technology, and is overwhelmingly promising compared to the previous era. It has been found that patients with oral diseases and systemic diseases have variations in the oral microbiome compared to normal subjects. This narrative review provides insight into the pathophysiological role that oral microbiome plays in influencing oral and systemic diseases, and updates the knowledge related to the oral microbiome over the past 30 years. A wide range of updates was provided with the latest knowledge of the oral microbiome to help researchers and clinicians in both academic and clinical aspects. The microbial community information can be utilized in non-invasive diagnosis and help develop a new paradigm in precision medicine, which will benefit human health in the era of post-metagenomics.

This paper describes some of the challenges that need to be addressed in order to develop collaborative spectrum sharing systems. The importance of these challenges stems from the assumption that rules for spectrum sharing can change after the deployment of radio networks and the whole system must be able to adapt to them. To address such a requirement, we used a policy-based approach in which transmissions are controlled by a policy interpreter system, and the policies can be modified during system operation. Our primary goal was to develop a prototype of such a system. In this paper, we outline the implementation of policy interpretation, automatic generation of transmission opportunities in case a request for transmission is denied by the policy reasoner, and the generation of rendezvous channels for the synchronization of otherwise asynchronously running software defined radios.

Galls are characteristic plant structures formed by hypertrophy (excessive increase in cell size) and/or hyperplasia (cell proliferation) induced by parasitic or pathogenic organisms. Insects are a major inducer of galls, and insect galls can occur on plant leaves, stems, floral buds, flowers, fruits, or roots. Many of these exhibit unique shapes, providing shelter and nutrients to the insects. To form unique gall structures, all-inducing insects are believed to secrete certain effector molecules and hijack host developmental programs. However, the molecular mechanisms of insect gall induction and development is still largely unknown because of the difficulty of studying non-model plants in the wild. Recent progress in next-generation sequencing has allowed us to determine the structure of biological processes in non-model organisms, including gall-inducing insects and their host plants. In this review, we first summarize the evolutionary aspects of gall-inducing life histories and their adaptive significance for insects and plants. Then, we briefly summarize recent progress regarding the molecular aspects of insect gall formation.

Purpose: Melanoma’s incidence is increasing, and elderly people could be significantly impacted since the majority occurs in people over 65 years of age. Combined targeted therapies (TT) are current standard regimen for BRAF mutated metastatic melanoma (MM). Except for subgroups of pivotal trials, little data are available for TT in this population. Materials and Methods: Outcomes were explored in real life patients from MelBase, a French multicentric biobank dedicated to the prospective follow-up of unresectable stage III or IV melanoma. Patients treated by BRAF TT and/or MEK TT combined or not, were included from 2013 to 2017 in 2 groups: group 1 <65-year-old (yo), group 2 >65 yo, analyzed for tolerance and efficacy. Results: 353 patients were included: 231 in group 1, 122 in group 2. Median follow-up was 12 months (M). Median time of treatment was 6.9 M. A total of 80% had at least one Adverse Effect (AE). Most frequent AE (all grades) were mainly skin and subcutaneous, general, and gastrointestinal disorders. A total of 31% of AE were grade 3–4: 28% in group 1 and 39% in group 2 (p = 0.05). No differences were observed in all AE grades proportion, dose modifications, interruptions, and discontinuations. For each group, median overall survival was 20.3 M (CI 95%: 15.5–27.9) and 16.3 M (CI: 14.5–26.9), respectively (p = 0.8). Median progression free survival was 7.8 M (6.4–9.9) and 7.7 M (CI: 5.8–11.3) (p = 0.4). Objective response rate was 59% and 50% (p = 0.6). Conclusion: This study on a large multicentric cohort is the first to assess that TT is well tolerated in elderly BRAF-mutated patients such as in patients younger than 65. Efficacy was similar between groups with outcomes reaching those from pivotal studies. There is thus no argument against using TT in elderly people, although an onco-geriatric opinion is welcome for the most vulnerable.

Blood-brain-barrier is a major obstacle in treating brain-related disorders as it does not allow to deliver drugs in the brain. In order to facilitate delivery of drugs in brain, we developed a method for predicting blood-brain-barrier penetrating peptides. These blood-brain barriers penetrating peptides (B3PPs) can act as therapeutic as well as drug delivery agents. We trained, tested, and evaluated our models on blood-brain-barrier peptides obtained from the B3Pdb database. First, we compute a wide range of peptide features then we select relevant peptide features. Finally, we developed numerous machine learning-based models for predicting blood-brain-barrier peptides using selected features. Our model based on random forest performed best on the top 80 selected features and achieved a maximum 85.08% accuracy with 0.93 AUROC. We also developed a web server, B3pred that implements our best models. It has three major modules that allow users to; i) predict B3PPs, ii) scanning B3PPs in a protein sequence, and iii) designing B3PPs using analogs. Our web server and standalone software is freely available at https://webs.iiitd.edu.in/raghava/b3pred/.

Brain, the most complex object known in the universe, uses few watts of power. To mimic it a nuclear power plant will be required and this power house controls the human body, single handedly. Surprisingly, “On the left side, nothing is right and on the right side there is nothing left”. Typically, there are two lateral halves of the brain: Left hemisphere and right hemisphere working distinctly. Left hemisphere is inclined towards logic; Right hemisphere is the root cause of imagination added with critical thinking. In situations like the current pandemic, COVID-19, it is the right half which tends to dominate the processing. This gives birth to mental stress, anxiety thus, aggravating the existing medical condition. Considering this pattern, a survey was conducted in Durg district of Chhattisgarh, which is one of the most hard hit epicentre of the COVID-19 second wave in India. According to this survey, it was revealed that largely women of all age groups (10-25, 26-40, 40 above) were right brained i.e. dominance of right over left hemisphere. Being more imaginative and creative thinkers they are more likely to suffer from mental issues than males. The aim of this research is to improve the mental wellbeing of the citizens in such threatening conditions. To prevent this situation awareness is a must and some stress relieving games have also been created.

Chronic pain is an unpleasant sensory and emotional experience that persists or recurs more than three months and may extend beyond the expected time of healing. Recently nociplastic pain has been introduced as a descriptor of mechanism of pain, which is due to disturbance of neural processing without actual or potential tissue damage, appearing to replace a concept of psychogenic pain. An interdisciplinary task force of the International Association for the Study of Pain (IASP) compiled a systematic classification of clinical conditions associated with chronic pain, which was published in 2018 and will officially come into effect in 2022 in the 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11) by the World Health Organization. ICD-11 offers the option for recording the presence of psychological or social factors in chronic pain; however, cognitive, emotional, and social dimensions in the pathogenesis of chronic pain are missing. Earlier pain disorder was defined as a condition with chronic pain associated with psychological factors, but it was replaced with somatic symptom disorder with predominant pain in Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in 2013. Recently clinical nosology is trending toward highlighting neurological pathology of chronic pain, discounting psychological or social factors in the pathogenesis of pain. This review article discusses components of the pain pathway, the component-based mechanisms of pain, central and peripheral sensitization, roles of chronic inflammation, and the involvement of tryptophan-kynurenine pathway metabolites, exploring participations of psychosocial and behavioral factors in central sensitization of diseases progressing into development of chronic pain, comorbid diseases that commonly present a symptom of chronic pain, and psychiatric disorders that manifest chronic pain without obvious actual or potential tissue damage.

Kenyan coffee is ranked among the best in the world and 99% is exported mainly to Germany, Sweden and Belgium, the USA and Saudi Arabia. Kenya produces quality Arabica beans which are generally recognized and upgraded with other relatively lower brands. In 1937, the Kenya Planters Cooperative Union (KPCU) was formed to represent small farmers' interests. In 1944, in the Coffee Board of Kenya (CBA) the law required smallholders to join local growing cooperatives run by government to reduce the power of large estates to control the board. Many reforms in the coffee industry have been initiated. This review explores evolution and existing coffee varieties in Kenya, the coffee value chain and the regions that grow coffee in Kenya. Additionally, the variety agronomics and appearance that encompass; quality potential at different altitudes, yield potential and nematodes susceptibility.

A novel cytoplasmic dye decolorizing peroxidase from Dictyostelium discoideum was investigated that oxidizes anthraquinone dyes, lignin model compounds and general peroxidase substrates like ABTS efficiently. Unlike related enzymes, an aspartate residue replaces the first glycine of the conserved GXXDG motif in Dictyostelium DyPA. In solution, Dictyostelium DyPA exists as a stable dimer with the side chain of Asp146 contributing to the stabilization of the dimer interface by extending the hydrogen bond network connecting two monomers. To gain mechanistic insights, we solved the Dictyostelium DyPA structures in the absence of substrate as well as in the presence of potassium cyanide and veratryl alcohol to 1.7, 1.85, and 1.6 Å resolution, respectively. The active site of Dictyostelium DyPA has a hexa-coordinated heme iron with a histidine residue at the proximal axial position and either an activated oxygen or CN^- molecule at the distal axial position. Asp149 is in an optimal conformation to accept a proton from H₂O₂ during the formation of compound I. Two potential distal solvent channels and a conserved shallow pocket leading to the heme molecule were found in Dictyostelium DyPA. Further, we identified two substrate-binding pockets per monomer in Dictyostelium DyPA at the dimer interface. Long-range electron transfer pathways associated with a hydrogen-bonding network that connects the substrate-binding sites with the heme moiety are described.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic which has been a topic of major concern to global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7, B.1.351, P1 and, B.1.617., which show in-creased transmissibility and resistance towards vaccines and therapies. Importantly, the likelihood of susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response or comorbidities needs greater attention. Herein, we provide a comprehensive perspective regarding ongoing vaccine (mRNA, protein-based, viral vector based etc.) and therapeutic (mono-clonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

Zika virus (ZIKV) is a mosquito-born flavivirus which human infection became relevant dur-ing recent outbreaks in Latin America, due to its unrecognized association with fetal neurologi-cal disorders. Currently there are no approved effective antivirals or vaccines for treatment or prevention of ZIKV infections. Amantadine and rimantadine are approved antivirals used against susceptible influenza A virus infections, that have been shown to have antiviral activity against other viruses, such as dengue virus (DENV). Here, we report the in vitro effectiveness of both amantadine and rimantadine hydrochlorides against ZIKV replication, resulting in a dose-dependent reduction in viral titers of a ZIKV clinical isolate and two different ZIKV refer-ence strains. Additionally, we demonstrate similar in vitro antiviral activity of these drugs against DENV-1 and yellow fever virus (YFV), although at higher drug concentrations for the later. ZIKV replication was inhibited at drug concentrations well below cytotoxic levels of both compounds, as denoted by the high selectivity indexes obtained with the tested strains. Further work is absolutely needed to determine a potential clinical use of these antivirals against ZIKV infections, but our results suggest the existence of a highly conserved mechanism across fla-vivirus, susceptible to be blocked by modified more specific adamantane compounds.

Coronavirus Disease 2019 (COVID-19) is the pandemic challenge of the last year. Cardiovascular involvement is one of the main characteristics of this disease. Due to endothelial damage, consequent phlogosis may increase a thrombosis risk. Cardiac injury may occur in different ways. However, an ischemic involvement of the cardiovascular system is rarely implied. In this regard, direct and indirect effects of COVID-19 are described. Nonetheless, the possible evaluation of the cardiovascular system may require different modalities. The cardiovascular evaluation may be different in emergency compared to critical care, requiring different tools for each setting. The aim of this review is to explore these modalities according to the different involvement of the cardiovascular system..

In this paper, we investigate the behaviour of a relativistic quantum oscillator under the effects of Lorentz symmetry violation determined by a tensor (KF)µναβ out of the Standard Model Extension. We analyze the quantum system under a Coulomb-type radial electric field and a uniform magnetic induced by Lorentz symmetry breaking effects under a Cornell-type potential, and obtain the bound states solution by solving the Klein-Gordon oscillator. We see a quantum effect due to the dependence of the angular frequency of the oscillator on the quantum numbers of the system, and the energy eigenvalues and the wave-function of the oscillator field get modified by the Lorentz symmetry breaking parameters as well as due to the presence of Cornell-type potential.

Deep convolutional neural network (CNN) has shown their great advantages in the single image deraining task. However, most existing CNN-based single image deraining methods still suffer from residual rain streaks and details lost. In this paper, we propose a deep neural network including the Multi-scale feature extraction module and the channel attention module, which are embed in the feature extraction sub-network and the rain removal sub-network respectively. In the feature extraction sub-network, the Multi-scale feature extraction module is constructed by a Multi-layer Laplacian pyramid, and is then integrated multi-scale feature maps by a feature fusion module. In the rain removal sub-network, the channel attention module, which assigns different weights to the different channels, is introduced for preserving image details. Experimental results on visually and quantitatively comparison demonstrate that the proposed method performs favorably against other state-of-the-art approaches

In contemporary design practices, there is a disconnect between the design techniques used for early-stage design experimentation and performance analysis, and those used for the manufacture and construction. This study addresses the problems in developing an integrated digital design workflow and provides a research framework for integrating environmental performance requirements with robotic manufacturing processes on a construction site. The proposed method enables the user to import a design surface, identify design parameters, set several environmental performance goals, and thereafter simulate and select a robotic building strategy. Based on these inputs, design alternatives are developed and evaluated, considering their robotically simulated constructibility, in terms of their performance criteria. To validate the proposed method, the design is evaluated in an experiment wherein a double-skin facade perforation is generated using the proposed methodology. The results suggest a heuristic feature to improve the simulated robotic constructibility. Moreover, the functionality of the prototype is demonstrated.

Disruption of the in utero environment can have dire consequences on fetal growth and development. Intrauterine growth restriction (IUGR) is a pathological condition by which the fetus deviates from its expected growth trajectory, resulting in low birth weight and impaired organ function. The developmental origins of health and disease (DOHaD) postulates that IUGR has lifelong consequences on offspring well-being, as human studies have established an inverse relationship between birth weight and long-term metabolic health. While these trends are apparent in epidemiological data, animal studies have been essential in defining the molecular mechanisms that contribute to this relationship. One such mechanism is cellular stress, a prominent underlying cause of the metabolic syndrome. As such, this review considers the role of oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and inflammation in the pathogenesis of metabolic disease in IUGR offspring. In addition, we summarize how uncontrolled cellular stress can lead to programmed cell death within the metabolic organs of IUGR offspring.

Islamic fundamentalism as a stream of Extremist claim a return to the true Islam and no compromise with the modern world has transformed the scene inside the country and in international relations as a threat and a serious contender in today's society. In fact, after September 11, 2001, expanded a serious debate about Islamic fundamentalism around the world. But it can be difficult to provide an overview of the history of political violence in which the phenomenon of Islamic fundamentalism as its starting point after September 11, is not mentioned. However, before the date mentioned in international studies, there are also traces of fundamentalism, But what is known today as the new form of Islamic fundamentalism, since 2011 and after the rise of the Middle East, was raised around the world and to create the challenges of Political sovereignty and security for the world's most strategic regions such as Europe and then Southeast Asia (especially Indonesia and Malaysia). Therefore, this research tries to answer this question: what is the most important factor in challenging the political sovereignty of states in Southeast Asia (especially Indonesia and Malaysia). The hypothesis is Islamic fundamentalism is a rival and threat against the sovereignty and national security of Indonesia and the Philippines. The result of this study explains and demonstrates the presence and role of Islamic fundamentalism in Indonesia and Malaysia as a serious challenge in the security-political reality of these countries. Therefore, this study seeks to recognize and address the challenges and threats that are faced by these two-country with the growth of Islamic fundamentalism.

The goal of clustering is to identify common structures in a data set by forming groups of homogeneous objects. The observed characteristics of many economic time series motivated the development of classes of distributions that can accommodate properties such as heavy tails and skewness. Thanks to its flexibility, the Skewed Exponential Power Distribution (also called Skewed Generalized Error Distribution) ensures a unified and general framework for clustering possibly skewed and heavy tailed time series. This paper develops a clustering procedure of model-based type, assuming that the time series are generated by the same underlying probability distribution but with different parameters. Moreover, we propose to optimally combine the estimated parameters to form the clusters with an entropy weighing $k$-means approach. The usefulness of the proposal is showed by means of application to financial time series, demonstrating also how the obtained clusters can be used to form portfolio of stocks.

Leishmania species are parasitic protozoans which cause leishmaniasis affecting millions of people worldwide. Sterols are important components of plasma and organellar membranes and serve as precursors for the synthesis of signaling molecules. In contrast to animals, Leishmania do not produce cholesterol but instead synthesize ergostane-based sterols. C14-demethylase is a key enzyme involved in the biosynthesis of sterols in Leishmania parasites and an important drug target. Its inactivation leads to multiple defects including increased plasma membrane fluidity, mitochondrion dysfunction, hypersensitivity to stress and reduced virulence. In this study, we revealed a novel role for sterol synthesis in the maintenance of RNA stability and translation. Sterol alteration in C14-demethylase knockout mutant leads to increased RNA degradation, reduced translation and impaired heat shock response. Thus, sterol biosynthesis plays an unexpected role in global gene regulation in Leishmania parasites.

Rhodes grass (Chloris gayana Kunth) is one of the most important forage grasses used throughout the tropical and subtropical regions of the world. Enhancing the conservation and use of genetic resources requires the development of knowledge and understanding about the existing global diversity of the species. In this study, 104 Rhodes grass accessions, held in trust in the ILRI forage genebank, were characterized using DArTSeq markers to evaluate the genetic diversity and population structure, and to develop representative subsets, of the collection. The genotyping produced 193,988 SNP and 142,522 SilicoDArT markers with an average polymorphic information content of 0.18 and 0.26, respectively. Hierarchical clustering using selected informative markers showed the presence of two and three main clusters using SNP and SilicoDArT markers, respectively, with a cophenetic correction coefficient of 82 %. Bayesian population structure analysis also showed the presence of two main subpopulations using both marker types indicating the existence of significant genetic variation in the collection. A representative subset, containing 21 accessions from diverse origins, was developed using the SNP markers. In general, the results revealed substantial genetic diversity in the Rhodes grass collection and the generated molecular information, together with the developed subset, should help enhance the management, use and improvement of Rhodes grass germplasm in the future.

G-protein-coupled receptors (GPCR) belong to a large family of molecules eliciting different responses to a variety of signaling molecules. These receptors participate in various physiologic pathways such as metabolism, growth, immune responses, inflammation, vision, taste, olfaction, neurotransmission and even and pathologic responses including chronic inflammatory and vascular diseases. Receptors contributing to the biological responses of renin-angiotensin system (RAS) are members of GPCR family. COVID-19-induced inflammatory cascade has been attributed to acute ACE2 downregulation and imbalance of proinflammatory ACE/AngII/AT1R and anti-inflammatory ACE2/angiotensin (1-7)/Mas axes in favor of the former. Some of the receptors contributing to activities of proteins in RAS including AT1R, AT2R and Mas receptors are members of GPCR family. It is notable that these receptors induce their effects both through G protein and β-arrestin pathway; the former exerts temporary and the latter more sustained effects. In addition to the imbalance of GPCR responses contributing to RAS activities, it has been suggested that SARS-CoV2 pathogenesis might be attributed to the activation of GPCRs or modulating G-proteins involved in adenosine-CFTR regulation system and epithelial Na channel function.This article includes a minireview about the physiological functions of GPCRs and their contribution to COVID-19.

Corrugated cardboard is an ecological material, mainly because, in addition to virgin cellulose fibers also the fibers recovered during recycling process are used in its production. However, the use of recycled fibers causes slight deterioration of the mechanical properties of the corrugated board. In addition, converting processes such as printing, die-cutting, lamination, etc. cause micro-damage in the corrugated cardboard layers. In this work, the focus is precisely on the crushing of corrugated cardboard. A series of laboratory experiments were conducted, in which the different types of single-walled corrugated cardboards were pressed in a fully controlled manner to check the impact of the crush on the basic material parameters. The amount of crushing (with a precision of 10 micrometers) was controlled by a precise FEMat device, for crushing the corrugated board in the range from 10 to 70 % of its original thickness. In this study, the influence of crushing on bending, twisting and shear stiffness as well as a residual thickness and edge crush resistance of corrugated board was investigated. Then, a procedure based on a numerical homogenization, taking into account a partial delamination in the corrugated layers to determine the degraded material stiffness was proposed. Finally, using the empirical-numerical method, a simplified calculation model of corrugated cardboard was derived, which satisfactorily reflects the experimental results.

Millions of people worldwide have an inadequate intake of selenium (Se) and zinc (Zn), and agronomic biofortification may minimise these problems. To evaluate the efficacy of combined foliar Se and Zn fertilisation in bread making wheat (Triticum aestivum L.), foliar Se (as NaSeO4) and soil and foliar Zn applications (as ZnSO4·7H2O) were tested individually and in all combinations. A 2-year field experiment was established in southern Spain under semiarid Mediterranean conditions, by following a split-split-plot design. The study year (2017/2018, 2018/2019) was considered as the main-plot factor, soil Zn application (50 kg Zn ha-1, nil Zn) as a subplot factor, and foliar application (nil, 10 g Se ha-1, 8 kg Zn ha-1, 10 g Se ha-1 + 8 kg Zn ha-1) as a sub-subplot factor. The best treatment to increase both Zn and Se concentration in both straw, 12.3- and 2.7-fold respectively, and grain, 1.2- and 4.1-fold respectively was the combined foliar application of Zn and Se. This combined Zn and Se application also increased on average the yield of grain, main product of this crop, by almost 26%. Therefore, bread-making wheat seems to be a very suitable crop to be used in biofortification programs with Zn and Se to alleviate their deficiency in both, people when using its grain and livestock when using its straw.

Increased severity of droughts, due to anthropogenic activities and global warming has imposed a severe threat on agricultural productivity ever before. This has further advanced the need for some eco-friendly approaches to ensure global food security. In this regard, application of plant growth-promoting rhizobacteria (PGPR) can be beneficial. PGPR through various mechanisms viz. osmotic adjustments, increased antioxidant, phytohormone production, regulating stomatal conductivity, increased nutrient uptake, releasing Volatile organic compounds (VOCs), and Exo-polysaccharide (EPS) production, etc not only ensures the plant’s survival during drought but also augment its growth. This review, extensively discusses the various mechanisms of PGPR in drought stress tolerance. We have also summarized the recent molecular and omics-based approaches for elucidating the role of drought responsive genes. The manuscript presents an in-depth mechanistic approach to combat the drought stress and also deals with designing PGPR based bioinoculants. Lastly, we present a possible sequence of steps for increasing the success rate of bioinoculants.

Background and objectives: In the current context, the 2021 presidential elections in Peru distance from the social objective, not being objectively represented, that is why we analyze their validity, we determine the distances between the parties if they are extreme, the correspondences with the departments and their prospects, in the surveys we propose which departments influence the results. Methods: We use a mixed methodology, qualitative analysis, it will be multidimensional with the support of statistical methods and programs such as R Studio, worddj, Gephi, and Iramuteq. The quantitative analysis will be through factor analysis, correspondence and discriminant analysis to the data of the election Results and conclusions: The textual analysis mentions that there are dimensions such as the social issue, the results of the surveys and democracy that are far apart, regarding the electoral issue. This inculcates to work both on the part of the organisms that carry out these processes, as well as the initiative of the candidates, and the media. Regarding the quantitative analysis, it is detailed that the representative parties must be greater than 4.0 million voters, to make representative parties at the national level. The classification regarding the percentage of votes is given in three groups, highlighting the independence of the Peru Libre political party in these . In the correspondence analysis we can detail that both Fuerza Popular and Peru Libre are extremist parties. The vast majority of Peruvian citizens have an ideological tendency, intermediate between both parties. The prospective projections with a cross section give a victory to the Peru Libre party. In the discriminant analysis, the sample for the surveys focuses on 7 departments that does not include the Peruvian capital.

Measuring bias is important as it helps identify flaws in quantitative forecasting methods or judgmental forecasts. It can, therefore, potentially help improve forecasts. Despite this, bias tends to be under-represented in the literature: many studies focus solely on measuring accuracy. Methods for assessing bias in single series are relatively well-known and well-researched, but for datasets containing thousands of observations for multiple series, the methodology for measuring and reporting bias is less obvious. We compare alternative approaches against a number of criteria when rolling-origin point forecasts are available for different forecasting methods and for multiple horizons over multiple series. We focus on relatively simple, yet interpretable and easy-to-implement metrics and visualization tools that are likely to be applicable in practice. To study the statistical properties of alternative measures we use theoretical concepts and simulation experiments based on artificial data with predetermined features. We describe the difference between mean and median bias, describe the connection between metrics for accuracy and bias, provide suitable bias measures depending on the loss function used to optimise forecasts, and suggest which measures for accuracy should be used to accompany bias indicators. We propose several new measures and provide our recommendations on how to evaluate forecast bias across multiple series.

Cotton is a potential and excellent candidate to balance both agricultural production and reme-diation of mercury-contained soil, as its main production fiber hardly involve into food chains. However, there is known rarely about the tolerance and response to Hg environments in cotton. In this study, The biochemical and physiological damages, in response to mercury (Hg), were investigated in upland cotton seedlings. The results on cottonseeds germination, indicated the germination rate were suppressed by high Hg levels, as the decrease of percentage was more than 10% at 1000 µM Hg. Shoots and roots’ growth were significantly inhibited above 10 µM Hg. The inhibitor rates (IR) in fresh weight were close between shoots and roots, whereas that in dry weight the root growth was more obviously influenced by Hg. In comparison of organs, the growth inhibition ranked as root > leaf > stem. The declining of translocation factor (TF) op-posed the Hg level even as low to 0.05 at 50 µM Hg. The assimilation of cotton plants was af-fected negatively by Hg toxicity, as evidenced from the performances on photosynthesis pig-ments (chlorophyll a and b) and gas exchange (Intercellular CO2 concentration (Ci), CO2 assimila-tion rate (Pn) and stomatal conductance (Gs)). Sick phenotypes on leaf surface included small white zone, shrinking and necrosis. Membrane lipid peroxidation and leakage were Hg dose-dependent as indicated by malondialdehyde (MDA) content and relative conductivity (RC) values in leaves and roots. More than 10 µM Hg damaged antioxidant enzyme system in both leaves and roots (P<0.05). Concludingly, 10 µM Hg post negative consequences to upland cotton plants in growth, physiology and biochemistry, whereas high phytotoxicity and damage ap-peared at more than 50 µM Hg concentration.

Land Use Land Cover (LULC) changes analysis is one of the most useful methodologies to understand how the land was used in the past years, what types of detections are to be expected in the future, as well as the driving forces and processes behind these changes. In Ethiopia, the rapidly changing of LULC is mainly due to population pressure, resettlement programs, climate change, and other human and nature-induced driving forces. Anthropogenic activities are the most significant factors adversely changing the natural status of the landscape and resources, which exerts unfavourable and adverse impacts on the environment and livelihood. The main goal of the present work is to review previous studies, discussing the spatio-temporal LULC changes in Ethiopian basins, to find out common points and gaps that exist in the current literature, to be eventually addressed in the future. Seventeen articles, published from 2011 to 2020, were selected and reviewed, focusing on LULC classification using ArcGIS and ERDAS imagine software by unsupervised and maximum likelihood supervised classification methods. Key informant interview (KII), focal group discussions (FGDs) and collection of ground truth data using ground positioning systems (GPS) for data validation were the major approaches discussed in most of the studies. All the analysed research showed that, during the last decades, Ethiopian lands changed to agricultural land use, waterbody, commercial farmland and built-up/settlement. Some parts of forest land, grazing land, swamp/wetland, shrubland, rangeland and bare/ rock out cropland cover class were changed to other LULC class types, mainly as a consequence of increasing anthropogenic pressure. In summary, these articles confirmed that LULC changes are a direct result of both natural and human influences. However, most of the study provided details of LULC for the past decades within a specific spatial location, while they did not address the challenge of forecasting future LULC changes at the basin scale.

A selection of 36 commercial probiotic fermented dairy products from UK and Europe markets were evaluated for the numbers, types and viability of Lactobacillus strains against the stated information on their packages. A comparative study was carried out on selectivity of MRS-Clindamycin, MRS-Sorbitol and MRS-IM Maltose, to select the right medium for enumeration of probiotic Lactobacillus. Based on selectivity of medium for recovery of the targeted lactobacilli and also simplicity of preparation, MRS-Clindamycin was chosen as the best medium for enumeration of probiotic Lactobacillus in fermented milks. The results of enumeration of lactobacilli showed that 22 out of a total 36 tested products contained more than 106 colony forming units/g at the end of their shelf- life, which comply with the recommended minimum therapeutic level for probiotics. Rep-PCR using primer GTG-5 was applied for initial discrimination of isolated strains, and isolates, which presented different band profile, were placed in different groups. The isolated Lactobacillus spp. were identified mainly as Lactobacillus acidophilus, Lactobacillus casei and Lactobacillus paracasei by analysis of partial sequences of the 16S ribosomal RNA and rpoA genes. In conclusion, it is unknown to recommend the adequate number of probiotic bacteria to be consumed to ensure the beneficial properties.

The authors present a stereotypical case presentation of x-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact Fibroblast Growth Factor 23 (FGF23) which lead to i) low serum phosphate levels, ii) increased fractional excretion of phosphorus, and iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in XLH patients is due to chronic hypophosphatemia. Additionally, XLH patients experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration’s (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.

With a highly efficient optical absorption capability, bismuth selenide (Bi2Se3) nanomaterial can be used as an outstanding photothermal agent for anti-tumor treatment and shows promise in the field of nanotechnology-based biomedicine. However, little research has been done on the relevant mechanism underlying the photothermal killing effect of Bi2Se3 nanomaterial. Herein, the photothermal effects of Bi2Se3 nanoparticles on A549 cells were explored with emphasis put on autophagy. Firstly, we characterized the structure and physicochemical property of the synthesized Bi2Se3 and confirmed their excellent photothermal conversion efficiency (35.72%), photostability, biocompatibility and ability of photothermal killing on A549 cells. Enhanced autophagy was detected in Bi2Se3-exposed cells under an 808 nm laser. Consistently, an elevated expression ratio of LC3-II to LC3-I, a marker of autophagy occurrence, was induced in Bi2Se3-exposed cells upon NIR irradiation. Meanwhile, the expression of cleaved-PARP was increased in the irradiated cells dependently on the exposure concentrations of Bi2Se3 nanoparticles. Pharmacological inhibition of autophagy by 3-methyladenine (3-MA) further strengthened the photothermal killing effect of Bi2Se3. Meanwhile, stress-related signaling pathways including p38 and SAPK/JNK were activated coupled with the attenuated PI3K/Akt signaling. Our study figures out that autophagy and the activation of stress-related signaling pathways were involved in the photothermal killing of cancerous cells by Bi2Se3, which provides a more understanding of photothermal nanomaterials.

Breast cancer is the most widespread malignancy in women from corner to corner of the world. Nanostructured lipid carrier (NLC) proved its efficacy in the treatment of cancer. NLC loaded with Imatinib (IMA) (NANIMA) was prepared and evaluated for in vitro efficacy in MCF-7 breast cancer cells. Hot homogenization method was used for the preparation of NANIMAs. Aqueous solution of surfactants (hot) was mixed with molten mixture of stearic acid and sesame oil (hot) under homogenization. The prepared NANIMAs were characterized and evaluated for size, polydispersity index, zeta potential, encapsulation efficiency, release studies, stability studies and MTT assay (cytotoxicity studies). The optimized NANIMA revealed particle size of 104.63 ± 9.55 d.nm, PdI of 0.227 ± 0.06 and EE of 99.79 ± 0.03. All NANIMAs revealed slow and sustained release behaviour. The surfactants used in the preparation of NANIMAs exhibited their effects on particle size, zeta potential, encapsulation efficiency, stability studies and release studies. The cytotoxicity studies unveiled 8.75 times increase in cytotoxicity for optimized NANIMA (IC50 = 6 µM) when compared with IMA alone (IC50 = 52.5 µM) on MCF-7 breast cancer cells. After this, NLC containing IMA possibly will be employed for the cure of breast cancer. A lesser amount of IMA loaded NLC will be sufficient than IMA alone for the treatment of breast cancer. Moreover, the patient will exhibit not as much of adverse effects as in case of IMA alone. Consequently, NANIMA could prove to be useful for effective therapeutic outcome in breast cancer treatment.