Engineering immunomodulatory and osteoinductive implant surfaces via mussel adhesion-mediated ion coordination and molecular clicking

Immune response and new tissue formation are important aspects of tissue repair. However, only a single aspect is generally considered in previous biomedical interventions, and the synergistic effect is unclear. Here, a dual-effect coating with immobilized immunomodulatory metal ions (e.g., Zn2+) and osteoinductive growth factors (e.g., BMP-2 peptide) is designed via mussel adhesion-mediated ion coordination and molecular clicking strategy. Compared to the bare TiO2 group, Zn2+ can increase M2 macrophage recruitment by up to 92.5% in vivo and upregulate the expression of M2 cytokine IL-10 by 84.5%; while the dual-effect of Zn2+ and BMP-2 peptide can increase M2 macrophages recruitment by up to 124.7% in vivo and upregulate the expression of M2 cytokine IL-10 by 171%. These benefits eventually significantly enhance bone-implant mechanical fixation (203.3 N) and new bone ingrowth (82.1%) compared to the bare TiO2 (98.6 N and 45.1%, respectively). Taken together, the dual-effect coating can be utilized to synergistically modulate the osteoimmune microenvironment at the bone-implant interface, enhancing bone regeneration for successful implantation.

On the dual effect of obstacles in preventing silo clogging in 2D

Placing an obstacle in front of a bottleneck has been proposed as a sound alternative to improve the flow of discrete materials in a wide variety of scenarios. Nevertheless, the physical reasons behind this behavior are not fully understood and the suitability of this practice has been recently challenged for pedestrian evacuations. In this work, we experimentally demonstrate that for the case of inert grains discharging from a silo, an obstacle above the exit leads to a reduction of clog formation via two different mechanisms: i) an alteration of the kinematic properties in the outlet proximities that prevents the stabilization of arches; and ii) an introduction of a clear anisotropy in the contact fabric tensor that becomes relevant when working at a quasi-static regime. Then, both mechanisms are encompassed using a single formulation that could be inspiring for other, more complex, systems.

RTA and LANA Competitively Regulate let-7a/RBPJ Signal to Control KSHV Replication

The recombination signal binding protein for immunoglobulin kappa J region (RBPJ) has a dual effect on Kaposi’s sarcoma-associated herpesvirus (KSHV) replication. RBPJ interaction with replication and transcription activator (RTA) is essential for lytic replication, while the interaction with latency-associated nuclear antigen (LANA) facilitates latent infection. Furthermore, our previous study found that LANA decreased RBPJ through upregulating miRNA let-7a. However, it is unclear whether RTA regulates the expression of RBPJ. Here, we show RTA increases RBPJ by decreasing let-7a. During KSHV replication, the RBPJ expression level was positively correlated with the RTA expression level and negatively correlated with the LANA expression level. The let-7a expression level was inverse to RBPJ. Knockdown of RBPJ inhibited the self-activation of RTA promoter and LANA promoter and weakened LANA’s inhibition of RTA promoter. Collectively, these findings indicate that RTA and LANA compete for let-7a/RBPJ signal to control the KSHV replication. Regulating the RBPJ expression level by RTA and LANA plays an important role during KSHV replication.

Audit Committee Competence and Earnings Management in Europe

This study analyses the association between the competence of audit committee members and earnings management in a sample of 142 non-financial firms from France, Germany, Italy, Spain, and the United Kingdom over the 2006–2013 period. We measure members’ competence through their dedication and expertise. We find that outside directorships have a dual effect, such that a balanced level of dedication to the audit committee (roughly two outside directorships) reduces earnings management. We examine four types of expertise: audit, non-audit accounting, non-accounting financial, and supervisory expertise. We find a negative relation between earnings management and the audit experience of committee members, and that the other types of expertise play no relevant role. We also find that the contribution of audit experts to curbing earnings management proves particularly important in smaller and less active committees, as well as in smaller and busier boards. Este estudio analiza la asociación entre la competencia de los miembros del Comité de Auditoría y la gestión de los beneficios en una muestra de 142 empresas no financieras de Francia, Alemania, Italia, España y el Reino Unido durante el período 2006-2013. Se mide la competencia de los miembros a través de su dedicación y experiencia. Se descubre que el cargo de consejero externo tiene un efecto doble, de modo que un nivel equilibrado de dedicación al comité de auditoría (aproximadamente dos cargos de consejero externo) reduce la gestión de beneficios. Se examinan igualmente cuatro tipos de experiencia: de auditoría, contable no relacionada con la auditoría, financiera no contable y de supervision, encontrándose una relación negativa entre la gestión de beneficios y la experiencia en auditoría de los miembros del comité, y que los otros tipos de experiencia no desempeñan ningún papel relevante. También se descubre que la contribución de los expertos en auditoría para limitar la gestión de beneficios resulta especialmente importante en los comités más pequeños y menos activos, así como en los consejos más pequeños y más ocupados.

Children and digital media

Digital revolution has transformed childhood very profusely. The goal of this work is to present the way digital technology influences education, in what way it shapes various dimensions of life and the identity of preschool children and the challenges upbringing parents are faced with. Numerous researches have indicated that digital media can be a worthy source of knowledge, encourage and develop various children's abilities and skills if they are used appropriately and under adult guidance. However, uncontrolled and excessive use of media in early children's age can potentially have extremely negative and harmful effects on the child's growth and development and endanger his/her health and happiness. Parents and other adults in charge of children’s care significantly affect children’s approach to the media and media content. This paper has concluded on the fact that social media has dual effect on the child; therefore, it is necessary to offer quality preventive programmes and workshops not only for parents and educators but also for children and youth. Keywords: Digital media, education, parents, the child, digital revolution.

Błok i Jung: inflacja ego („Wiersze o Przepięknej Pani”)

According to depth psychology, whose pioneer is C.G. Jung, inflation is an emotional state, most often triggered by a dream, manifested by an increase in sexual urge, a feeling of higher energy, power and fascination. Ego inflation can have a dual effect on the individual who experiences it: positive, which is associated with the possibility of establishing contact with archetypes as elements of the collective unconscious, and negative, leading to a sense of possession. In both cases, which often occur together, the key to understanding this unique state of psychic energy is contact with symbols, previously latent in the psychic genotype. In the creative process, as well as in crucial moments of life, the ego acquires the special privilege of insight into the unrecognised realms of the unconscious, which leads to a kind of emotional explosion, a feeling of ecstasy. The ego of the creator, stunned by new possibilities and filled with psychic energy, undergoes excessive growth, “swelling”. Carl Jung calls this state being possessed by the unconscious complex. In the case of Alexander Blok, one can speak of being possessed by the archetype of the Eternal Feminine – Anima, which is proven in the cycle Verses About the Beautiful Lady (1901–1902). The symbol of the Beautiful Lady unites within its archetypal structure various kinds of psychological oppositions (consciousness and unconsciousness, inner woman and inner man, ecstasy and fear). The Beautiful Lady as the numinous element of the poet’s psychic structure acquires the status of an energetic dominant or the centre of the unconscious.

Nanoviricides platform technology based NV-CoV-2 polymer increases the half-life of Remdesivir in vivo

So far, there are seven coronaviruses identified that infect humans and only 4 of them belong to the beta family of coronavirus (HCoV-HKU1, SARS-CoV-2, MERS-CoV and SARS-CoV). SARS family are known to cause severe respiratory disease in humans. In fact, SARS-CoV-2 infection caused a pandemic COVID-19 disease with high morbidity and mortality. Remdesivir (RDV) is the only antiviral drug so far approved for COVID-19 therapy by the FDA. However, the efficacy of RDV in vivo is limited due to its low stability in presence of plasma. This is the report of analysis of the non-clinical pharmacology study of NV-CoV-2 (Polymer) and NV-CoV-2-R (Polymer encapsulated Remdesivir) in both infected and uninfected rats with SARS-CoV-2. Detection and quantification of NV-CoV-2-R in plasma samples was done by MS-HPLC chromatography analyses of precipitated plasma samples from rat subjects. (i) NV-CoV-2-R show RDV peak in MS-HPLC chromatography, whereas only NV-CoV-2 does not show any RDV-Peak, as expected. (ii) NV-CoV-2 polymer encapsulation protects RDV in vivo from plasma-mediated catabolism. (iii) Body weight measurements of the normal (uninfected) rats after administration of the test materials (NV-CoV-2, and NV-CoV-2-R) show no toxic effects on them. Our platform technology based NV-387-encapsulated-RDV (NV-CoV-2-R) drug has a dual effect on coronaviruses. First, NV-CoV-2 itself as an antiviral regimen. Secondly, RDV is protected from plasma-mediated degradation in transit, rendering altogether the safest and an efficient regimen against COVID-19.