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The next generation of mobile communication system will allow a plethora of new services and use cases. By offering support for high throughput connections, low latency response and massive number of connections, the fifth generation of the mobile network will trigger applications unseen in any other network. However, one important application scenario is not being properly addressed by the players responsible for the mobile networks’ standardization, that is the remote and rural areas network. This scenario requires large cells with high throughput, flexibility to opportunistically exploit free bands below 1 GHz and spectrum agility to change the operational frequency when an incumbent is detected. Incipient actions are being considered for the Release 17 but based on the new radio specification as starting point. The limitations imposed by orthogonal waveforms in the physical layers hinder the exploitation of vacant TV channels in rural and remote areas. 5G-RANGE, a Brazil-Europe bilateral cooperation project, aims at conceiving, implementing and deploying an innovative mobile network, designed to provide reliable and cost-effective connection in these regions. This network can be seamlessly integrated with the other 5G scenarios, closing the connectivity gap between the urban, rural and remote areas. Hence, 5G-RANGE network is an interesting complementary solution for beyond 5G standards. This paper presents the major achievements of the 5G-RANGE project, from the design of the physical, medium access control and network layers, to the field demonstrations. The paper also covers the business models that can be used to make the deployment of this technology a reality.

Tacrolimus is a macrolide immunosuppressive agent, and tacrolimus ointment has been used as therapy for atopic dermatitis worldwide. Given that the immunosuppressive action of tacrolimus raises at least the theoretical potential for an increased risk of skin cancer, accurate assessment of the risk of developing skin cancer by tacrolimus ointment is necessary. The objective of the present study is to investigate the skin tumorigenic potential of commercially available tacrolimus ointment. We conducted a skin carcinogenicity study using an initiation-promotion (I/P) mouse model. Our study consisted of six groups (26 mice/group): sham control, absorptive ointment (AO), macrogol ointment (MO), tacrolimus ointment (TO) vehicle control, TO 0.03%, and TO 0.1%. Following a single administration of 7,12-dimethylbenz[α] anthracene (DMBA) to the dorsal skin of mice as an initiator, 12-O-tetra-decanoylphorbol-13-acetate (TPA) as a promoter and the test drugs were topically administered for 18 weeks. The incidence of skin hyperplasia in the TO 0.03% and TO 0.1% groups was reduced compared with both control groups (P < 0.05). Further, the incidence of skin neoplasia in the TO 0.03% (P < 0.05) and TO 0.1% groups (P < 0.01) was reduced in a dose-dependent manner compared with the sham control group. Tumor promotion effects on skin carcinogenesis were observed in the AO group, whereas inhibitory effects were observed in the MO group. TO 0.03% and TO 0.1% dose-dependently inhibit tumor induction in an I/P mouse model of skin tumors.

Migration and proliferation of endothelial cells (ECs) and smooth muscle cells (SMCs) contribute to the response to injury in damaged and atherosclerotic vessels. These events might be regulated by cellular interactions with extracellular matrix through the expression and activation of integrins. To study the functions of beta 1 integrins in the vessel wall, we used monoclonal antibody (MAb) 15/7, which recognizes an activation epitope of beta 1 integrin subunits, and MAb 8A2, which induces a high affinity form of beta 1 integrins recognized by MAb 15/7. Immunohistochemical analyses were done on samples of normal baboon saphenous arteries and from arteries subjected to balloon injury. EC and SMC expressed the activation epitope of beta 1 integrin in uninjured arteries. By contrast, in balloon-injured arteries 6 weeks after injury, regenerating EC did not express the activation epitope, and there was no decrease in the expression of total beta 1 integrin, whereas SMC migrating into the intima exhibited decreased expression of the total and activated beta 1 integrin. Flow cytometer analysis of cultured cells indicated that baboon EC and SMC weakly express the activation epitope of beta 1 integrin. Next, we determined by utilizing MAb 8A2 the effects of increased expression of activation epitope of beta 1 integrin on the functions of SMC and EC. The activation of beta 1 integrins on SMC induced by MAb 8A2 enhanced SMC adhesion and suppressed SMC migration in a Boyden chamber assay. SMC proliferation was inhibited by MAb 8A2 dose-dependently. Similarly, MAb 8A2-induced activation of beta 1 integrins on EC suppressed EC migration into a wound. However, MAb 8A2 did not affect the basic fibroblast growth factor-induced proliferation of EC, although it blocked the decrease in EC number caused by the removal of basic fibroblast growth factor. These results suggest that activation of beta 1 integrins in vascular cells is regulated in a cell-type dependent manner and plays an important role in modulating vascular cell functions.