Spatial and diagrammatic reasoning is a significant part not only of logical abilities, but also of logical studies. The authors of this paper consider some novel trends in studying this type of reasoning. They show that there are the following two main trends in spatial logic: (i) logical studies of the distribution of various objects in space (logic of geometry, logic of colors, etc.); (ii) logical studies of the space algorithms applied by nature itself (logic of swarms, logic of fungi colonies, etc.).
In this paper, we discuss the initial state of the universe at the Big Bang. By using the ideas of Freedman in the proof of the disk embedding theorem for 4-manifolds, we describe the corresponding spacetime as a gravitational instanton. The spatial space is a fractal space (wild embedded 3-sphere). Then, we construct the quantum state from this fractal space. This quantum state is part of the string algebra of Ocneanu. There is a link between the Jones polynomial and Witten’s topological field theory. Using this link, we are able to determine the physical theory (action) as the Chern–Simons functional. The gauge fixing of this action determines the foliation of the spacetime and the smoothness properties. Finally, we determine the quantum symmetry of the quantum state to be the enveloped Lie algebra Uq(sl2(C)), where q is the fourth root of unity.
Protection against the effects of space radiation poses great technical and medical challenges for future human missions and is of interparliamentary concern requiring alignment of multiple scientific, clinical, and ethical parameters. In our article, we highlight the inadequacy of current countermeasures, which may justify the use of human enhancement (HE), or biomedical technologies to increase astronaut protection from the harmful space environment, protect lifespan longevity and increase the chance of survival during spaceflight or as colonists on other worlds. The deleterious effects of space radiation on the human body may justify even the most radical forms of HE, which may incorporate gene editing. As a thought experiment, we propose that an ethical assessment should depend on the anchor and purpose of the mission and we discuss differences and similarities between the bioethics of space missions and military ethics on Earth.
Studying the anticancer activity of 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones towards cell lines of different cancer types allowed the identification of hit‐compounds inhibiting the growth of daunorubicin‐ (CEM‐DNR, IC50 = 0.32–1.28 µM) and paclitaxel‐resistant (K562‐TAX, IC50 = 0.21–1.23 µM) cell lines, with favorable therapeutic indexes. The studied compounds induced apoptosis and cellular proliferation in treated CCRF‐CEM cells. The hit compounds were shown to induce mitotic arrest by interacting with tubulin, inhibiting its polymerization by binding to the colchicine binding site. New 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones with submicromolar cytotoxic activity (IC50 0.10–2.12 µM) and favorable therapeutic index towards CCRF‐CEM, CEM‐DNR, HCT‐116, HCT116p53−/−, K‐562, K562‐TAX, and U2OS cells were identified. Hit compounds 3, 10, and 12 induced mitotic arrest by interacting with microtubules, inhibiting their polymerization by binding to the colchicine binding site.
The proposed donor heart selection guidelines provide an evidence-based and expert-consensus recommendations for the selection of donor hearts following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review.
Grasping the identity of hybrids, that is beings which cross the binarism of nature and technology (e.g. genetically-modified organisms (GMOs), syn-bio inventions, biomimetic projects), is problematic since it is still guided by self-evident dualistic categories, either as artefacts or as natural entities. To move beyond the limitations of such a one-sided understanding of hybrids, we suggest turning towards the categories of affordances and the juxtaposition of needs and patterns of proper use, as inspired by the Heideggerian version of phenomenology. Drawing upon selected concepts by Heidegger, we argue that hybrids can be conceptualised as a regenerative design and use to serve the planet. We argue that the ideal type of non-exploitative account of hybrids consists of the adaptive approach to the environment, which does not, however, exclude the possibility of designing and constructing new beings. We also point out that hybrids undermine the divide of being destructive/regenerative which marks the boundaries of nature and technology.
[This corrects the article DOI: 10.3389/fphar.2022.896706.].
The empirical literature provides strong evidence supporting the relation of various innovation activities, including business innovation. The literature, however, continues to be limited in the context of developing countries, especially considering different types of business innovations. The aim of the present research is to fill the gap in the literature concerning the impact of research and development (R&D) cooperation and various types of investments in innovation for the creation of sustainable business innovation in small- and medium-sized enterprises (SMEs). Particular emphasis in this study is placed on the differences in types of business innovations. The research is based on cross-sectional data (n = 406) collected by the CATI (Computer-Assisted Telephone Interview) method in a Polish peripheral region (Subcarpathian Voivodeship). To examine the relation between different innovation activities and the creation of business innovation, logistic regression was employed. The results show that the outputs of both R&D cooperation and investments are highly dependent on the innovation type. The outcomes suggest that R&D cooperation might be a driver of the implementation of development activities and organizational innovation, while the expenditures on machinery and equipment lead to a greater probability for the implementation of process innovation and development activities. We also found that expenditures on marketing activities and investments in the implementation of new solutions may have an impact on business innovation implementation.
Natural cosmetics are becoming more and more popular every day. For this reason, this work investigates the properties of mushroom extracts, which are not as widely used in the cosmetics industry as plant ingredients. Water extracts of Grifolafrondosa (Maitake), Hericiumerinaceus (Lion’s Mane) and Ganoderma lucidum (Reishi) were tested for their antioxidant properties, bioactive substances content, skin cell toxicity, ability to limit TEWL, effect on skin hydration and pH, and skin irritation. Our research showed that Maitake extract contained the highest amount of flavonoids and phenols, and also showed the most effective scavenging of DPPH and ABTS radicals as well as Chelation of Fe2+and FRAP radicals, which were 39.84% and 82.12% in a concentration of 1000 µg/mL, respectively. All tested extracts did not increase the amount of ROS in fibroblasts and keratinocytes. The addition of mushroom extracts to washing gels reduced the irritating effect on skin, and reduced the intracellular production of free radicals, compared with the cosmetic base. Moreover, it was shown that the analyzedcosmetics had a positive effect on the pH and hydration of the skin, and reduced TEWL.
Cancerous diseases are rightfully considered among the most lethal, which have a consistently negative effect when considering official statistics in regular health reports around the globe. Nowadays, metallic nanoparticles can be potentially applied in medicine as active pharmaceuticals, adjustable carriers, or distinctive enhancers of physicochemical properties if combined with other drugs. Boron dipyrromethene (BODIPY) molecules have been considered for future applications in theranostics in the oncology field, thus expanding the potential of conceivable applicability. Hence, taking into account positive practical features of both metal-based nanostructures and BODIPY derivatives, the present study aims to gather recent results connected to BODIPY-conjugated metallic nanoparticles. This is with respect to their expediency in the diagnosis and treatment of tumor ailments as well as in sensing of heavy metals. To fulfill the designated objectives, multiple research documents were analyzed concerning the latest discoveries within the scope of BODIPY-based nanomaterials with particular emphasis on their utilization for diagnostical sensing as well as cancer diagnostics and therapy. In addition, collected examples of mentioned conjugates were presented in order to draw the attention of the scientific community to their practical applications, elucidate the topic in a consistent manner, and inspire fellow researchers for new findings.
Malignant melanoma is a very aggressive tumour with the ability to metastasize at an early stage. Therefore, early detection is of great importance. Multiphoton tomography is a new non-invasive examination method in the clinical diagnosis of skin alterations that can be used for such early diagnosis. In this paper, a method for automated evaluation of multiphoton images of the skin is presented. The following features at the cellular and subcellular level were extracted to differentiate between malignant melanomas, lesions, and healthy skin: cell symmetry, cell distance, cell density, cell and nucleus contrast, nucleus cell ratio, and homogeneity of cytoplasm. The extracted features formed the basis for the subsequent classification. Two feature sets were used. The first feature set included all the above-mentioned features, while the second feature set included the significantly different features between the three classes resulting from a multivariate analysis of variance. The classification was performed by a Support Vector Machine, the k-Nearest Neighbour algorithm, and Ensemble Learning. The best classification results were obtained with the Support Vector Machine using the first feature set with an accuracy of 52 % and 79.6 % for malignant melanoma and healthy skin, respectively. Despite the small number of subjects investigated our results indicate that the proposed automatic method can differentiate malignant melanoma, lesions, and healthy skin. For future clinical application, an extended study with more multiphoton images is needed.
Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects joints but should be considered as a syndrome that also includes extra-articular manifestations and comorbidities. Human-derived induced pluripotent stem cells (hiPSCs) and their differentiated derivatives may be of special interest in the investigation of complex pathophysiology of RA. In this study, we demonstrate and compare the generation of hiPSC from peripheral blood mononuclear cells (PBMC) and fibroblast-like synoviocytes (FLS) from RA patients. Application of three-dimensional cardiac microtissues constructed from RA specific iPSC-derivatives may be a useful approach to investigate RA comorbidities and cardiac protection or toxicity of anti-rheumatic drugs.
This paper uses the methodological scheme of contingency tables to explore polarisation in the Polish labour market. We use a large database of online job offers published on selected Polish job portals in the period 2017–2019, whereas most of the studies on the polarisation hypothesis are based on employment data. The main advantage of our microdata is the use of information on the required skills of the vacancy. The contingency table allows us to generate clusters of vacancies whose attributes tend to appear jointly. The study reveals that office skills do not offer a particular advantage in an automated labour market, while information and computer technology skills and communication skills seem to have a shield effect in such an environment. In addition, a cluster of transversal skills –self-organisational, technical and interpersonal skills– constitutes an important requirement for most job offers. These skills should be widely developed within the educational system, at different levels.
Development of cancer drug-resistance is still an ongoing problem in the modern anticancer treatment. Therefore, there is a need to search for a new active substance, which may become a potential anticancer agent. 4-Thiazolidinones are well-described substances with cytotoxicity against cancer cells in vitro. Therefore, the aim of this study was to evaluate the effect of two 4-thiazolidinone-based derivatives (Les-2769 and Les-3266) on the PPARγ-dependent cytotoxicity in normal human skin fibroblasts (BJ) and squamous cell carcinoma (SCC-15) in vitro. The data obtained showed a cytotoxic effect of Les-2769 and Les-3266 used in micromolar concentrations on SCC-15 and BJ cells, manifesting by a decrease in the metabolic activity, an increase in the release of lactate dehydrogenase, and caspase-3 activity. The co-treatment of the cells with Les-3266 and an antagonist (GW9662) or an agonist (rosiglitazone) of the PPARγ receptor induced changes in the above-mentioned parameters in the BJ and SCC-15 cells, compared to the Les-3266 alone exposure; this was not found in the Les-2769-treated cells. The further analysis of the compounds indicated changes in the expression of the PPARγ, KI67, and NF-κB genes. Moreover, the tested compounds caused an increase in the level of PPARγ mRNA expression in a similar way to rosiglitazone in SCC-15, which may indicate the affinity of the compounds for PPARγ. Molecular docking is consistent with experimental in vitro data about the potential agonistic activity of Les-2769 and Les-3266 towards PPARγ receptors. Summarizing, the anticancer effect of both compounds was observed in the SCC-15 cells in vitro; moreover, the mechanism of action of Les-3266 in cells is mediated probably by interaction with the PPARγ receptor pathway, which needs in-depth study.
Elastin-derived peptides (EDPs) contain replications of the Val-Gly-Val-Ala-Pro-Gly (VGVAPG) hexapeptide. It has been described that the VGVAPG peptide induces reactive oxygen species (ROS) production in murine monocytes and astrocytes, human fibroblasts, and the human neuroblastoma (SH-SY5Y) cell line. To date, there is growing evidence that calcium channel blockers (CCBs) reduce oxidative stress and development of inflammation in the nervous system. Therefore, the aim of the present study was to evaluate the impact of such CCBs as Nifedipine, Verapamil, and MK-801 on the expression of peroxisome proliferator-activated receptor (Pparγ), i.e. ROS-related and inflammation-related proteins, in mouse astrocytes exposed in vitro to the VGVAPG peptide. The experiments showed that Nifedipine or MK-801 used in co-treatment with the VGVAPG peptide potentiated the effect of this peptide on the Pparγ level after the 24-h and 48-h treatment. Moreover, all studied compounds decreased the VGVAPG-induced caspase-1 activity in both time intervals. The data also showed that the VGVAPG peptide decreased the interleukin 1 beta (IL-1β) level in both studied time intervals. Upon a short-time exposure, the use of CCBs intensified the decrease in IL-1β stimulated by the VGVAPG peptide, opposite to the longer treatment. Moreover, the VGVAPG peptide decreased the IL-1βR1 level in both studied time intervals. After 24 h, Nifedipine and Verapamil potentiated the effect of the VGVAPG peptide. The VGVAPG peptide decreased the catalase (Cat) protein expression only after 24 h, whereas CCBs did not affect the expression of Cat induced by the VGVAPG peptide. The VGVAPG peptide increased the expression of the superoxide dismutase 1 (Sod1) protein. After 24 h of exposure, Nifedipine and Verapamil potentiated the increase in the Sod1 protein expression. Finally, our data showed that VGVAPG did not change the level of estradiol (E2) in the astrocytes. Interestingly, Nifedipine and Verapamil in co-treatment with VGVAPG increased the E2 level. Summarizing, it can be assumed that increased amounts of the VGVAPG during lifetime can play a certain role in calcium channel functioning in neurodegenerative diseases.
In this study, the effect of ozonation process on the poly(ADP-ribose) polymerase 1 gene expression (PARP-1) and related the NADPH metabolism in strawberry fruit during storage was determined. Our results showed that ozonation with gas at both 10 and 100 ppm concentrations increased the expression of PARP-1 in the fruit during storage. Furthermore, the ozonation process initially increased the level of NAD+ and NADH in the fruit, which corresponds to a higher ATP level. The storage of the fruit in an ozone atmosphere also contributed to increased activity of the NAD+ kinase, leading to increased levels of NADP+. In turn, the higher activity of glucose-6-phosphate dehydrogenase caused the ozonated fruit to show a higher level of NADPH. However, as the storage period extended and thus with increasing expression of PARP-1 in the ozonated fruit, the level of NAD+ decreased. In general, the ozonated fruit, which had a higher level of NADPH, showed a higher content of reduced glutathione, which in turn contributed to an increase in the antioxidant activity of the fruit and, ultimately, to a lower accumulation of reactive oxygen species.
The aim of the article is to identify, on the basis of the analysis of the literature and the results of empirical research, the expectations of enterprises towards suppliers regarding the improvement of their operational processes. It can be noticed that manufacturing companies, while improving their processes, also require actions in this area from suppliers. The article presents the results of empirical research conducted using the computer-assisted telephone interview (CATI) technique in medium and large manufacturing companies operating in Poland. The results of these studies show that manufacturing companies focus their expectations towards suppliers mainly on the improvement of quality control processes (deliveries, semi-finished products, as well as the finished products). The research results presented in the article have several important implications for representatives of science and business.
The paper analyzes and successively assesses the problem of information delays in a sample logistics system, in which customer inquiries are sent to adjacent or dedicated units in the logistics chain. Within such a framework time and unit costs of customer service and inquiry are analyzed. A detailed model of the logistics system is thus elaborated using a mathematical approach and its graphical representation. The accompanying case study includes the analysis of the detailed situation in which two models are compared that do not differ in the structure of logistic units but are characterized by different information flow paths. Simulation results are presented through a thorough graphic, numerical and descriptive analysis. Finally, the problem of information transmission in the logistics system is summarized.
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