Fyn is widely involved in diverse cellular physiological processes, including cell growth and survival, and has been implicated in the regulation of energy metabolism and the pathogenesis of diabetes mellitus through multiple pathways. Fyn plays a role in increasing fat accumulation and promoting insulin resistance, and it also contributes to the development of diabetic complications such as diabetic kidney disease and diabetic retinopathy. The primary mechanism by which Fyn modulates lipid metabolism is that it inhibits AMP-activated protein kinase (AMPK). Additionally, it affects energy homeostasis through regulating specific signal pathways affecting lipid metabolism including pathways related to CD36, through enhancement of adipocyte differentiation, and through modulating insulin signal transduction. Inflammatory stress is one of the fundamental mechanisms in diabetes mellitus and its complications. Fyn also plays a role in inflammatory stress-related signaling cascades such as the Akt/GSK-3β/Fyn/Nrf2 pathway, exacerbating inflammation in diabetes mellitus. Therefore, Fyn emerges as a promising therapeutic target for regulating glucolipid metabolism and alleviating type 2 diabetes mellitus. This review synthesizes research on the role of Fyn in the regulation of energy metabolism and the development of diabetes mellitus, while exploring its specific regulatory mechanisms.
In this study, we advance our exploration of Apolipoprotein A-I (apoA-I) peptide analogs (APAs) for their application in nanodisc (ND) assembly, focusing on the dynamic conformational characteristics and the potential for drug delivery. We explore APA-ND interactions with an emphasis on curcumin encapsulation, utilizing molecular dynamic simulations and in vitro assessments to evaluate the efficacy of various APA-ND formulations as drug carriers. The methodological approach involved the generation of three unique apoA-I α-11/3 helical mimics, resulting in fifteen distinct APAs. Their structural integrity was rigorously assessed using ColabFold-AF2, with particular attention to pLDDT and pTM scores. Extensive molecular dynamics simulations, covering 1.7 μs across 17 ND systems, were conducted to investigate the influence of APA sequence variations on ND stability and interactions. This study reveals that the composition of APAs, notably the presence of Proline, Serine, and Tryptophan, significantly impacts ND stability and morphology. Oligomeric APAs, in particular, demonstrated superior stability and distinct interaction patterns compared to their monomeric counterparts. Additionally, hydrodynamic diameter measurements over eight weeks indicated sequence-dependent stability, highlighting the potential of specific APA configurations for sustained colloidal stability. In vitro study successfully encapsulated curcumin in [AA]<sub>3</sub>/DMPC ND formulations, revealing concentration-dependent stability and interaction dynamics. The findings underscore the remarkable capability of APA-NDs to maintain structural integrity and efficient drug encapsulation, positioning them as a promising platform for drug delivery. The study concludes by emphasizing the tunability and versatility of APA-NDs in drug formulation, potentially revolutionizing nanomedicine by enabling customized APA sequences and ND properties for targeted drug delivery.
Generating SPARQL queries from natural language questions is challenging in Knowledge Base Question Answering (KBQA) systems. The current state-of-the-art models heavily rely on fine-tuning pretrained models such as T5. However, these methods still encounter critical issues such as triple-flip errors (e.g., (subject, relation, object) is predicted as (object, relation, subject)). To address this limitation, we introduce <b>TSET</b> (<b>T</b>riplet <b>S</b>tructure <b>E</b>nhanced <b>T</b>5), a model with a novel pretraining stage positioned between the initial T5 pretraining and the fine-tuning for the Text-to-SPARQL task. In this intermediary stage, we introduce a new objective called Triplet Structure Correction (TSC) to train the model on a SPARQL corpus derived from Wikidata. This objective aims to deepen the model’s understanding of the order of triplets. After this specialized pretraining, the model undergoes fine-tuning for SPARQL query generation, augmenting its query-generation capabilities. We also propose a method named “semantic transformation” to fortify the model’s grasp of SPARQL syntax and semantics without compromising the pre-trained weights of T5. Experimental results demonstrate that our proposed TSET outperforms existing methods on three well-established KBQA datasets: LC-QuAD 2.0, QALD-9 plus, and QALD-10, establishing a new state-of-the-art performance (95.0% <i>F</i>1 and 93.1% QM on LC-QuAD 2.0, 75.85% <i>F</i>1 and 61.76% QM on QALD-9 plus, 51.37% <i>F</i>1 and 40.05% QM on QALD-10).
Enrico La Spina, Sebastiano Giallongo, Cesarina Giallongo
et al.
Chronic myeloproliferative neoplasms encompass the BCR-ABL1-negative neoplasms polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). These are characterized by calreticulin (CALR), myeloproliferative leukemia virus proto-oncogene (MPL) and the tyrosine kinase Janus kinase 2 (JAK2) mutations, eventually establishing a hyperinflammatory tumor microenvironment (TME). Several reports have come to describe how constitutive activation of JAK-STAT and NFκB signaling pathways lead to uncontrolled myeloproliferation and pro-inflammatory cytokines secretion. In such a highly oxidative TME, the balance between Hematopoietic Stem Cells (HSCs) and Mesenchymal Stromal Cells (MSCs) has a crucial role in MPN development. For this reason, we sought to review the current literature concerning the interplay between HSCs and MSCs. The latter have been reported to play an outstanding role in establishing of the typical bone marrow (BM) fibrotic TME as a consequence of the upregulation of different fibrosis-associated genes including PDGF- β upon their exposure to the hyperoxidative TME characterizing MPNs. Therefore, MSCs might turn to be valuable candidates for niche-targeted targeting the synthesis of cytokines and oxidative stress in association with drugs eradicating the hematopoietic clone.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
The Monroe Doctrine occupies a unique place in the US history. It became one of the key foreign policy documents of its time and provided the basis for a wide variety of interpretations of the United States’ role and goals in the international arena at turning points of world history. One of these moments was the turn of the 1910s−1920s, when a new Versailles-Washington order of international relations was emerging. In the US public discourse, this period was marked by intense debates between supporters of the Democratic President V. Wilson and his isolationist opponents. Both Republicans and Democrats constantly referred to the Monroe Doctrine, on the one hand, to justify their own views on US foreign policy in the new conditions, and, on the other hand, to refute the arguments of their political opponents. The controversy surrounding the Monroe Doctrine has been reflected in publications in periodicals and analytical journals, as well as in cartoons. Studying these materials, it is possible to trace the evolution of the approaches of American politicians, experts, editors, and journalists to the Monroe Doctrine. The arguments of the Republicans against the ‘internationalist’ interpretation of the Monroe Doctrine that emerged in the face of the changing global context after the First World War are of particular interest. The study shows that at the initial stage of discussions (1920), the Monroe Doctrine was used by the Republicans primarily to criticize W. Wilson’s concept of international relations in general and his position on the League of Nations in particular. At the next stage (1921−1923), the debate focused around the need to revise the Monroe Doctrine itself, that aroused due to new trends in the development of international relations in the Far East and, in particular, because of the increasing competition between the United States and Japan. The author identifies several main approaches to the interpretation of the Monroe Doctrine formulated during the public debate in 1921−1923. It is shown that, despite significant divergences of view, both isolationists and internationalists eventually came to broader interpretations of the Monroe Doctrine, recognizing the need to extend its principles to the entire Asia-Pacific region.
Mosaic Provenance reports about the provenance of the Design for the Mosaic Web Open Knowledge Initiative. It helps to demonstrate that the Mosaic Web Design was traceably derived using proven approaches from evidence-based domains. The traceable nature of the derivation supports ongoing improvement of the Design, based on feedback from open peer review.
J. Ernesto Solanes, Adolfo Muñoz, Luis Gracia
et al.
This work proposes a new interface for the teleoperation of mobile robots based on virtual reality that allows a natural and intuitive interaction and cooperation between the human and the robot, which is useful for many situations, such as inspection tasks, the mapping of complex environments, etc. Contrary to previous works, the proposed interface does not seek the realism of the virtual environment but provides all the minimum necessary elements that allow the user to carry out the teleoperation task in a more natural and intuitive way. The teleoperation is carried out in such a way that the human user and the mobile robot cooperate in a synergistic way to properly accomplish the task: the user guides the robot through the environment in order to benefit from the intelligence and adaptability of the human, whereas the robot is able to automatically avoid collisions with the objects in the environment in order to benefit from its fast response. The latter is carried out using the well-known potential field-based navigation method. The efficacy of the proposed method is demonstrated through experimentation with the Turtlebot3 Burger mobile robot in both simulation and real-world scenarios. In addition, usability and presence questionnaires were also conducted with users of different ages and backgrounds to demonstrate the benefits of the proposed approach. In particular, the results of these questionnaires show that the proposed virtual reality based interface is intuitive, ergonomic and easy to use.
Sylvia L. R. Wood, Kyle T. Martins, Véronique Dumais-Lalonde
et al.
Designing effective habitat and protected area networks, which sustain species-rich communities is a critical conservation challenge. Recent decades have witnessed the emergence of new computational methods for analyzing and prioritizing the connectivity needs of multiple species. We argue that the goal of prioritizing habitat for multispecies connectivity should be focused on long-term persistence of a set of species in a landscape or seascape. Here we present a review of the literature based on 77 papers published between 2010 and 2020, in which we assess the current state and recent advances in multispecies connectivity analysis in terrestrial ecosystems. We summarize the four most employed analytical methods, compare their data requirements, and provide an overview of studies comparing results from multiple methods. We explicitly look at approaches for integrating multiple species considerations into reserve design and identify novel approaches being developed to overcome computational and theoretical challenges posed by multispecies connectivity analyses. There is a lack of common metrics for multispecies connectivity. We suggest the index of metapopulation capacity as one metric by which to assess and compare the effectiveness of proposed network designs. We conclude that, while advances have been made over the past decade, the field remains nascent by its ability to integrate multiple species interactions into analytical approaches to connectivity. Furthermore, the field is hampered its ability to provide robust connectivity assessments for lack of a clear definition and goal for multispecies connectivity conservation.
Andi Kurniawan Nugroho, Dinar Mutiara Kusumo Nugraheni, Terawan Agus Putranto
et al.
When the blood flow to the arteries in brain is blocked, its known as Ischemic stroke or blockage stroke. Ischemic stroke can occur due to the formation of blood clots in other parts of the body. Plaque buildup in arteries, on the other hand, can cause blockages because if it ruptures, it can form blood clots. The b-1000 Diffusion Weighted (DW) Magnetic Resonance Imaging (MRI) image was used in a general examination to obtain an image of the part of the brain that had a stroke. In this study, classifications used several variations of layer convolution to obtain high accuracy and high computational consumption using b-1000 Diffusion Weighted (DW) MR in ischemic stroke types: acute, sub-acute and chronic. Ischemic stroke was classified using five variants of the Convolutional Neural Network (CNN) architectural design, i.e., CNN1–CNN5. The test results show that the CNN5 architectural design provides the best ischemic stroke classification compared to other architectural designs tested, with an accuracy of 99.861%, precision 99.862%, recall 99.861, and F1-score 99.861%.
Reframing Tomorrow presents the Design for the Mosaic Web Open Knowledge Initiative. This is a new opportunity for delivery of the United Nations' Sustainable Development Goals in an ethical, politically-acceptable, cost-effective and timely manner.
This article analyses compliance of the post-Soviet Baltic States with
the EU liberal-democratic standards, at both institutional and value levels. The authors
prove that fulfilment of the Copenhagen criteria for EU accession did not determine an
enhancement of the quality of democracy in Estonia, Latvia and Lithuania. This study
highlights that, in recent years, the Baltic States have entered a phase of stagnation of
liberal-democratic transformations and that they need a more active position of the
state on institutional reforms and resocialization of citizens to strengthen adherence to
the political and legal values that the EU is based on. The article emphasises how the
global financial crisis of 2008, the European migration crisis (2015) and the current
coronavirus pandemic have all had an impact on the quality of democracy in the Baltic
States. The authors focus on the incomplete process of value reforming among the Baltic
population against the EU liberal-democratic standards. The article highlights that the
post-totalitarian rotation of values in Estonia, Latvia and Lithuania is slow and faces
rejection of European liberal-democratic values to a greater or lesser extent. It underlines
the preservation of the totalitarian (Soviet) vestiges of political culture, which contradict
the EU paradigm of values and prevent the Baltic States from improving the quality of
democracy. It is noted that, in terms of the radicalization level in defending national
interests, the Baltic countries take the intermediate position between the Nordic and the
V4 countries, particularly Hungary and Poland that develop illiberal democracy patterns.
Chicken liver is a main protein source to prepare attractant for dog food. However, animal proteins are costly. Seeking high quality and low-cost protein sources has been a goal for the industry. Mushroom Lentinus edodes (L. edodes) and Mealworm Tenebrio molitor (T. molitor) are novel protein sources, showing high potential as raw material of attractants. In this paper, chicken liver, L. edodes, and T. molitor were used as three different protein sources to prepare attractants. Their palatability to dogs were then compared. Firstly, the enzymatic hydrolysis process of three proteins was optimized, with a degree of hydrolysis of 54.82%, 36.10% and 30.14% for chicken liver, L. edodes, and T. molitor respectively. Secondly, volatile compounds of three attractants were identified by HS-SPME/GC-MS and SDE/GC-MS. Using OAV and PLRS method, it was found that bis(2-methyl-3-furyl) disulfide, indole, methional, 2-(methyl thio) phenol, γ-butyrolacton, furfuryl alcohol, acetic acid and isovaleraldehyde were the key components. Although both T. molitor and L. edodes attractant showed less palatability than that of chicken liver, they could be readily improved via adding key palatable volatile compounds. The ingestion rate of dog food with attractant showed a similar trend and was higher than that of food without attractant.
Dhanach Dhirachaikulpanich, Dhanach Dhirachaikulpanich, Xin Li
et al.
We report for the first time an integrated transcriptomic analysis of RPE/choroid dysfunction in AMD (mixed stages) based on combining data from publicly available microarray (GSE29801) and RNAseq (GSE135092) datasets aimed at increasing the ability and power of detection of differentially expressed genes and AMD-associated pathways. The analysis approach employed an integrating quantitative method designed to eliminate bias among different transcriptomic studies. The analysis highlighted 764 meta-genes (366 downregulated and 398 upregulated) in macular AMD RPE/choroid and 445 meta-genes (244 downregulated and 201 upregulated) in non-macular AMD RPE/choroid. Of these, 731 genes were newly detected as differentially expressed (DE) genes in macular AMD RPE/choroid and 434 genes in non-macular AMD RPE/choroid compared with controls. Over-representation analysis of KEGG pathways associated with these DE genes mapped revealed two most significantly associated biological processes in macular RPE/choroid in AMD, namely the neuroactive ligand-receptor interaction pathway (represented by 30 DE genes) and the extracellular matrix-receptor interaction signaling pathway (represented by 12 DE genes). Furthermore, protein-protein interaction (PPI) network identified two central hub genes involved in the control of cell proliferation/differentiation processes, HDAC1 and CDK1. Overall, the analysis provided novel insights for broadening the exploration of AMD pathogenesis by extending the number of molecular determinants and functional pathways that underpin AMD-associated RPE/choroid dysfunction.
Alefsi David Sanchez-Reinoso, Edgar Alvaro Ávila-Pedraza, Hermann Restrepo
The objective of this review is to show in a general way how biochar (BC) can be obtained and its effects on the physicochemical properties of soils and physiological behavior of cultivated plants. BC is a product rich in carbon that comes from the pyrolysis of biomass, generally of vegetable origin. BC is obtained by the decomposition of organic matter exposed to temperatures between 200-900 ºC in an atmosphere with low oxygen availability (pyrolysis), which can be slow, intermediate or fast. Depending on the biomass and the temperature used in its production, BC can contain high levels of elements such as carbon, nitrogen, oxygen, hydrogen, sulfur, among others. The main sources to produce biochar are forest, agroindustrial and manure residues. BC quality and physical-chemical characteristics will depend not only on the type of waste or plant material for production, but also on the plant photosynthetic apparatus. The high carbon contents present in organic matter, which are more resistant to biological and chemical decomposition, are stabilized by the pyrolysis process. When incorporated into the soil, BC remains stable for longer periods of time and is not volatilized into the atmosphere; this allows BC to be considered as an important compound for the mitigation of the impacts of polluting substances. Additionally, it has been found that BC application improves the physicochemical characteristics of the soil, including fertility. This improvement generates positive responses in the physiological behavior of cultivated plants such as the increase of germination, accumulation of dry matter, photosynthetic rate, yield and quality of the harvested organ. BC use opens important doors for the sustainable management of agriculture in Colombia. It can be considered in production systems exposed to heavy metals such as vegetables and perennial species, in order to reduce the impact of these substances on human health.
Kelvin H.-C. Chen, Pei-Chun Liu, Tsun-Ren Chen
et al.
A series of cyclometalated iridium(III) complexes that have the general formula [(C^N)<sub>2</sub>Ir(NR)(X)] (C^N = monoanionic bidentate cyclometalating ligands; NR = pyridine derivatives; X = Cl<sup>−</sup> or I<sup>−</sup>) are designed, prepared, and applied for the transformation of toluene to benzaldehyde using a clean, highly efficient, and environmentally-friendly process. The activation energies that are needed for the catalytic oxidation of toluene when using these complexes as catalysts are quite low: between 22.9 and 30.8 kcal mol<sup>−1</sup>. The catalytic frequencies (TOF) are fairly high (up to 7.0 × 10<sup>2</sup> h<sup>−1</sup>) with excellent reliability, and the turnover number (TON) can reach 4.2 × 10<sup>3</sup> after 6 h of processing time. Catalytic tests, X-ray absorption near-edge structure (XANES), and kinetic modeling are used to derive detailed insights into the characteristics of the catalysts and their effects on the reactions that are featured in the catalytic oxidation of toluene.
Healthy environment is a basic need for toddlers to have a normal growth and development. Living around a landfill area will greatly impact to their morbidity and mortality rate. Although this condition may not be avoidable, it is assumed that maternal knowledge about toddler health influenced by maternal education level may be an important factor to keep their toddlers healthy. The aim of this study was to know the correlation between housewives education level and maternal knowledge about the toddler health. The study was conducted at RW 04 Kelurahan Kedaung Wetan, Tangerang from May to June 2013. A descriptive correlational with survey technique was applied in this study using 69 housewives with toddler who were selected by simple random sampling. An instrument consists of 27 points of true and false statements was used to obtain data. A strong correlation between housewives education levels and maternal knowledge about toddler health with correlation coefficient of 0.79 resulted from this study. As the conclusion, the housewives education level gave 62.4% contribution to maternal knowledge about toddler health.
Loes M. J. Kroon-Batenburg, John R. Helliwell, Brian McMahon
et al.
A topical review is presented of the rapidly developing interest in and storage options for the preservation and reuse of raw data within the scientific domain of the IUCr and its Commissions, each of which operates within a great diversity of instrumentation. A résumé is included of the case for raw diffraction data deposition. An overall context is set by highlighting the initiatives of science policy makers towards an `Open Science' model within which crystallographers will increasingly work in the future; this will bring new funding opportunities but also new codes of procedure within open science frameworks. Skills education and training for crystallographers will need to be expanded. Overall, there are now the means and the organization for the preservation of raw crystallographic diffraction data via different types of archive, such as at universities, discipline-specific repositories (Integrated Resource for Reproducibility in Macromolecular Crystallography, Structural Biology Data Grid), general public data repositories (Zenodo, ResearchGate) and centralized neutron and X-ray facilities. Formulation of improved metadata descriptors for the raw data types of each of the IUCr Commissions is in progress; some detailed examples are provided. A number of specific case studies are presented, including an example research thread that provides complete open access to raw data.
Under the conditions of teamwork there appears a strong need for the coordination of such a work, for enticing and synchronizing of individual activities as well as searching for optimal solutions that will secure the accomplishment of common goals. In these circumstances it seems the management to be a necessity coming from the nature and character of teamwork. That is why management has always been a subject of interest in science and everyday human practice.
How much the management will be successful depends on a series of factors among which a significant place is attributed to the personality traits of a manager. That is why one justifies the endeavours of many authors to identify the personality features a person should possess in order to be a good manager. Therefore, there are differentiated numerous lists of “necessary attributes” of successful managers neither of which can be considered universal nor discarded completely.
In this work an attempt has been made in order personality traits of a good manager to be identified through an empirical approach and to establish the fact whether the meaning contributed to certain attributes is also changed along with the changes in our society.
Farzaneh Yousefi, Iraj I. Nabipour, Alireza Raeisi
et al.
The museum of health is a place that presents health science and human body and any other subjects that can affect human health. In this museum visitors can learn the mechanisms and functions of human body and learn how to protect and take care of their bodies. They can also learn several diseases and their consequences on human body and how to fight against them. This museum is a big step for improvement of general society health level by increasing society’s health knowledge. In this article structure, departments and also benefits of the health museum are evaluated.