Synthesis and Biological Evaluation of Ionizable Lipid Materials for the In Vivo Delivery of Messenger RNA to B Lymphocytes

B lymphocytes regulate several aspects of immunity including antibody production, cytokine secretion, and T‐cell activation; moreover, B cell misregulation is implicated in autoimmune disorders and cancers such as multiple sclerosis and non‐Hodgkin's lymphomas. The delivery of messenger RNA (mRNA) into B cells can be used to modulate and study these biological functions by means of inducing functional protein expression in a dose‐dependent and time‐controlled manner. However, current in vivo mRNA delivery systems fail to transfect B lymphocytes and instead primarily target hepatocytes and dendritic cells. Here, the design, synthesis, and biological evaluation of a lipid nanoparticle (LNP) system that can encapsulate mRNA, navigate to the spleen, transfect B lymphocytes, and induce more than 60 pg of protein expression per million B cells within the spleen is described. Importantly, this LNP induces more than 85% of total protein production in the spleen, despite LNPs being observed transiently in the liver and other organs. These results demonstrate that LNP composition alone can be used to modulate the site of protein induction in vivo, highlighting the critical importance of designing and synthesizing new nanomaterials for nucleic acid delivery.     

Effect of copolymers modifying PVC on its physical and mechanical properties and its UV-radiation resistance. III. Changes in thermal stability of PVC films modified by MMA/MA,VC/VAC,MBS or ABS induced by UV-irradiation

The influence of UV-radiation on thermal stability of PVC films, depending on the type and quantity of modifying copolymers, was studied. It was found that UV radiation can induce various changes in thermal stability of PVC decreasing its dehydrochlorination temperature T⁰₁ while increasing temperature of decomposition T⁰₂. Particularly distinct changes in sampels containing VC/VAC indicate that even 1% of this copolymer accelerates the photodehydrochlorination and the processes which decrease the temperature of decomposition of PVC. Smaller changes than in pure PVC in thermal parameters in samples containing ABS after irradiation show that this copolymer increases the PVC resistance to UV radiation. Films containing MBS, ABS, MMA/MA reveal the largest changes in T⁰₁ after irradiation in the case of a content of 1% of these copolymers in the samples. In the case of bigger quantity (3 to 10%) the changes are smaller and may even diversify their direction. These copolymers, contrary to VC/VAC, make PVC films a little turbid indicating the limited compatibility of both components. Hence, the conclution is that the structure of a film, depending on compatibility of components and changing with their differing concentration, has decisive influence on the thermal and photochemical processes.     

Influence of a photoinitiator on the photochemical stability of poly(methyl methacrylate) studied with fourier transform infrared spectroscopy

Fourier transform infrared (FTIR) spectroscopy was used to investigate the effect of a commercial photoinitiator [2,2‐dimethoxy‐2‐phenylacetophenone (DMPA); Irgacure 651, Ciba, Basel, Switzerland] incorporated into poly(methyl methacrylate) (PMMA). Pure PMMA and modified PMMA (containing 5% DMPA) films were exposed to a xenon lamp in air. Qualitative and quantitative analyses of the recorded FTIR absorption spectra were done. This allowed us to determine the differences in the course of polymer photooxidative degradation occurring in PMMA and PMMA doped with DMPA. We found that the initiator added to polymer film enhanced the efficiency of the formation of the photooxidized products containing functional groups of different types, which could be distinguished by mathematical treatment of the FTIR spectra. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

In at the Deep End of Firm Internationalization

• The purpose of this research is to examine the consequences of top management team (TMT) internationalization: why and under what conditions can TMT nationality diversity be beneficial?
• On the basis of the upper echelons theory from the strategic leadership literature, the relationship between the TMT nationality diversity and firm performance in the strategic context of firm internationalization is investigated in moderated multiple regressions models (MMR) for a sample of Dutch, Swiss, and UK companies.
• The study findings suggest that the TMT nationality diversity becomes advantageous only in firms with high degree of internationalization. Companies have to be strongly committed to foreign markets so that the benefits of the TMT nationality diversity can materialize.
• The arising managerial implication is that the TMT nationality diversity can be a powerful tool in building a firm’s competitive advantage, provided that companies are strongly exposed to the international environment. The study also provides corroborative evidence that the search for moderating and mediating variables in the TMT demography research represents a step in the right direction.