Numerical simulations in 3-dimensions of reaction–diffusion models for brain tumour growth

We work with a well-known model of reaction–diffusion type for brain tumour growth and accomplish full 3-dimensional (3d) simulations of the tumour in time on two types of imaging data, the 3d Shepp–Logan head phantom image and an MRI T1-weighted brain scan from the Internet Brain Segmentation Repository. The source term is such that we have logistic growth. These simulations are obtained using standard finite difference approximations with novel calculations to increase speed and accuracy. Moreover, biological background to the model, its well-posedness together with a variational formulation are given. The variational formulation enable the feasibility of different derivations and modifications of the model

INVESTMENT OF SOCIAL ENTREPRENEURSHIP IN UKRAINE: CURRENT ISSUES OF LEGAL REGULATION

Abstract. The article deals with the research of the creation of conditions for the socialization of economic relations in modern Ukraine — legal regulation of social entrepreneurship investment. The Ukrainian state actively implements world economic trends and legal standards into national practice. These include social entrepreneurship and its legal support. It is stated that the main priorities of social entrepreneurship today are: development of social innovations, ecology, health care, education, vocational training, employment of people with disabilities, welfare, development of territories, culture, etc. In Ukraine, social entrepreneurship has a somewhat undeveloped character, primarily due to a lack of funds for its development. There is no specific legal regulation of social entrepreneurship in Ukraine. The main form of domestic social entrepreneurship is a charitable activity of public organizations. It is emphasized that the success of projects in the field of social entrepreneurship depends to a large extent on foreign investment. Investor rights in Ukraine are protected by advanced legislation and, despite bureaucratic obstacles, are guaranteed by the state. It is noted that the analysis of domestic economic and legal practice indicates the existence of social and legal prerequisites for successful investment in social entrepreneurship. Among these prerequisites, the following are outlined: public willingness and organizational support of the state, international assistance, presence of interested social groups, and availability of special draft laws that should stimulate the formation, development, and activity of social enterprises as the main form of social entrepreneurship. Attention is drawn to the fact that the draft Law of Ukraine «On Social Enterprise» changes social entrepreneurship ideology from charitable to entrepreneurial activity, which is combined with the implementation of innovation and solution of social problems. In particular, this approach is attractive for both internal and external investors and is the basis for social entrepreneurship’s future success. It is concluded that the proposed research can be of interest to both potential investors and investors who are already working in Ukraine and would like to develop or diversify their activities. Keywords: investments, social entrepreneurship, protection of investor rights, economic and legal preconditions for social entrepreneurship. JEL classіfіcatіon E20 G20 O35 K20 Formulas: 0; fig.: 0; tabl.: 0; bibl.: 21

Achieving Carbon Neutrality – The Role of Heterogeneous Environmental Regulations on Urban Green Innovation

This article examines the impact of heterogeneous environmental regulations on urban green innovation using panel data from 285 prefecture-level cities in mainland China from 2008 to 2019. From the perspective of green patents, this article utilizes a two-way fixed-effect model and the mediation effect model to examine the mechanism of the impact of heterogeneous environmental regulations on urban green innovation in China. Results show that the urban green innovation development in China is relatively slow and can be easily influenced by national policies. More specifically, the relationship between the command-based environmental regulation and urban green innovation presents an inverted non-linear U-shaped model, whereas the relationship between the market-based and voluntary environmental regulation presents a positive U-shaped model. Further investigation of this mechanism concludes that the progression of regional green innovation is primarily accelerated by technological development, effective energy allocation, and industrial structural upgrading. However, the implementation of relevant environmental regulations varies, resulting in various green innovation progression rates. Therefore, in order to achieve the carbon neutrality goal that China proposes, the effectiveness of environmental regulation implementation should be improved. Moreover, the development of various environmental regulation tools should be better coordinated.fals

In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis

International audiencePSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in severalLeishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice.We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in aL. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L.braziliensis (CCLb) or visceral leishmaniasis due to L. donovani (CVLd) and in healthy individuals. Healthy individuals weresubdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantuminfection) or non immune/naive individuals (HLR: Healthy Low Responders), depending on whether they produce high orlow levels of IFN-c in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detectedin sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-c, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-a in more. No significant cytokine response wasobserved in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increasein CD4+ T cells producing IFN-c after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between thepercentage of IFN-c-producing CD4+ T cells and the released IFN-c. We showed that the LaPSA-38S protein was able toinduce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infectionindicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacityof Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infectio

AKT Signaling Mediates IGF-I Survival Actions on Otic Neural Progenitors

Background: Otic neurons and sensory cells derive from common progenitors whose transition into mature cells requires the coordination of cell survival, proliferation and differentiation programmes. Neurotrophic support and survival of post-mitotic otic neurons have been intensively studied, but the bases underlying the regulation of programmed cell death in immature proliferative otic neuroblasts remains poorly understood. The protein kinase AKT acts as a node, playing a critical role in controlling cell survival and cell cycle progression. AKT is activated by trophic factors, including insulin-like growth factor I (IGF-I), through the generation of the lipidic second messenger phosphatidylinositol 3-phosphate by phosphatidylinositol 3-kinase (PI3K). Here we have investigated the role of IGF-dependent activation of the PI3K-AKT pathway in maintenance of otic neuroblasts. Methodology/Principal Findings: By using a combination of organotypic cultures of chicken (Gallus gallus) otic vesicles and acoustic-vestibular ganglia, Western blotting, immunohistochemistry and in situ hybridization, we show that IGF-I-activation of AKT protects neural progenitors from programmed cell death. IGF-I maintains otic neuroblasts in an undifferentiated and proliferative state, which is characterised by the upregulation of the forkhead box M1 (FoxM1) transcription factor. By contrast, our results indicate that post-mitotic p27Kip-positive neurons become IGF-I independent as they extend their neuronal processes. Neurons gradually reduce their expression of the Igf1r, while they increase that of the neurotrophin receptor, TrkC. Conclusions/Significance: Proliferative otic neuroblasts are dependent on the activation of the PI3K-AKT pathway by IGF-I for survival during the otic neuronal progenitor phase of early inner ear development

Emergence and Modular Evolution of a Novel Motility Machinery in Bacteria

Bacteria glide across solid surfaces by mechanisms that have remained largely mysterious despite decades of research. In the deltaproteobacterium Myxococcus xanthus, this locomotion allows the formation stress-resistant fruiting bodies where sporulation takes place. However, despite the large number of genes identified as important for gliding, no specific machinery has been identified so far, hampering in-depth investigations. Based on the premise that components of the gliding machinery must have co-evolved and encode both envelope-spanning proteins and a molecular motor, we re-annotated known gliding motility genes and examined their taxonomic distribution, genomic localization, and phylogeny. We successfully delineated three functionally related genetic clusters, which we proved experimentally carry genes encoding the basal gliding machinery in M. xanthus, using genetic and localization techniques. For the first time, this study identifies structural gliding motility genes in the Myxobacteria and opens new perspectives to study the motility mechanism. Furthermore, phylogenomics provide insight into how this machinery emerged from an ancestral conserved core of genes of unknown function that evolved to gliding by the recruitment of functional modules in Myxococcales. Surprisingly, this motility machinery appears to be highly related to a sporulation system, underscoring unsuspected common mechanisms in these apparently distinct morphogenic phenomena

Using and Reporting the Delphi Method for Selecting Healthcare Quality Indicators: A Systematic Review

OBJECTIVE: Delphi technique is a structured process commonly used to developed healthcare quality indicators, but there is a little recommendation for researchers who wish to use it. This study aimed 1) to describe reporting of the Delphi method to develop quality indicators, 2) to discuss specific methodological skills for quality indicators selection 3) to give guidance about this practice. METHODOLOGY AND MAIN FINDING: Three electronic data bases were searched over a 30 years period (1978-2009). All articles that used the Delphi method to select quality indicators were identified. A standardized data extraction form was developed. Four domains (questionnaire preparation, expert panel, progress of the survey and Delphi results) were assessed. Of 80 included studies, quality of reporting varied significantly between items (9% for year's number of experience of the experts to 98% for the type of Delphi used). Reporting of methodological aspects needed to evaluate the reliability of the survey was insufficient: only 39% (31/80) of studies reported response rates for all rounds, 60% (48/80) that feedback was given between rounds, 77% (62/80) the method used to achieve consensus and 57% (48/80) listed quality indicators selected at the end of the survey. A modified Delphi procedure was used in 49/78 (63%) with a physical meeting of the panel members, usually between Delphi rounds. Median number of panel members was 17(Q1:11; Q3:31). In 40/70 (57%) studies, the panel included multiple stakeholders, who were healthcare professionals in 95% (38/40) of cases. Among 75 studies describing criteria to select quality indicators, 28 (37%) used validity and 17(23%) feasibility. CONCLUSION: The use and reporting of the Delphi method for quality indicators selection need to be improved. We provide some guidance to the investigators to improve the using and reporting of the method in future surveys

Off-target effects of bacillus Calmette–Guérin vaccination on immune responses to SARS-CoV-2: implications for protection against severe COVID-19

Background and objectives: Because of its beneficial off-target effects against non-mycobacterial infectious diseases, bacillus Calmette–Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID-19). Using samples from participants in a placebo-controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID-19, we investigated the immunomodulatory effects of BCG on in vitro immune responses to SARS-CoV-2. Methods: This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID-19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ-irradiated SARS-CoV-2-infected or mock-infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single-cell immunophenotyping was made by flow cytometry. Results: BCG vaccination, but not placebo vaccination, reduced SARS-CoV-2-induced secretion of cytokines known to be associated with severe COVID-19, including IL-6, TNF-α and IL-10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4+ and CD8+ T cells, and an activation of eosinophils in response to SARS-CoV-2. Conclusions: The immunomodulatory signature of BCG’s off-target effects on SARS-CoV-2 is consistent with a protective immune response against severe COVID-19