FRCA: A Fuzzy Relevance-Based Cluster Head Selection Algorithm for Wireless Mobile Ad-Hoc Sensor Networks

Clustering is an important mechanism that efficiently provides information for mobile nodes and improves the processing capacity of routing, bandwidth allocation, and resource management and sharing. Clustering algorithms can be based on such criteria as the battery power of nodes, mobility, network size, distance, speed and direction. Above all, in order to achieve good clustering performance, overhead should be minimized, allowing mobile nodes to join and leave without perturbing the membership of the cluster while preserving current cluster structure as much as possible. This paper proposes a Fuzzy Relevance-based Cluster head selection Algorithm (FRCA) to solve problems found in existing wireless mobile ad hoc sensor networks, such as the node distribution found in dynamic properties due to mobility and flat structures and disturbance of the cluster formation. The proposed mechanism uses fuzzy relevance to select the cluster head for clustering in wireless mobile ad hoc sensor networks. In the simulation implemented on the NS-2 simulator, the proposed FRCA is compared with algorithms such as the Cluster-based Routing Protocol (CBRP), the Weighted-based Adaptive Clustering Algorithm (WACA), and the Scenario-based Clustering Algorithm for Mobile ad hoc networks (SCAM). The simulation results showed that the proposed FRCA achieves better performance than that of the other existing mechanisms

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis

Phase I Study of a B Cell-Based and Monocyte-Based Immunotherapeutic Vaccine, BVAC-C in Human Papillomavirus Type 16-or 18-Positive Recurrent Cervical Cancer

BVAC-C is a B cell-based and monocyte-based immuno-therapeutic vaccine transfected with a recombinant human papillomavirus (HPV) 16/18 E6/E7 gene and loaded with alpha-galactosyl ceramide, which is a natural killer T cell ligand. This phase I study sought to determine the tolerability and immunogenicity of BVAC-C in platinum-resistant recurrent cervical cancer patients. Patients with HPV 16-positive or 18-positive recurrent or persistent cervical cancer who had received at least one prior platinum-based combination chemotherapy were enrolled. BVAC-C was injected intravenously three times every four weeks, and dose escalation was planned in a three-patient cohort design at doses of 1 x 10(7), 4 x 10(7), or 1 x 10(8) cells/dose. Eleven patients were enrolled, and six (55%) patients had received two or more lines of platinum-based chemotherapy prior to enrollment. Treatment-related adverse events (TRAEs) were observed in 21 cycles. Most TRAEs were mild fever (n = 6.55%) or myalgia (n = 4.36%). No dose-limiting toxicities occurred. The overall response rate was 11% among nine patients evaluable, and the duration of response was 10 months. Five patients (56%) achieved a stable disease for 4.2-11 months as their best overall response. The median progression-free survival in all patients was 6.8 months (95% CI, 3.2 to infinite months), and the overall survival rate at 6 and 12 months was 89% (95% CI, 71 to 100%) and 65% (95% CI, 39 to 100%), respectively. BVAC-C induced the activation of natural killer T cells, natural killer cells, and HPV 16/18 E6/E7-specific T cells upon vaccination in all patients evaluated. BVAC-C was well tolerated and demonstrated a durable anti-tumor activity with an immune response in HPV 16-positive or 18-positive recurrent cervical carcinoma patients. A Phase 2 efficacy trial is currently underway.Y

The Chimeric Adenovirus (Ad5/35) Expressing Engineered Spike Protein Confers Immunity against SARS-CoV-2 in Mice and Non-Human Primates

Several COVID-19 platforms have been licensed across the world thus far, but vaccine platform research that can lead to effective antigen delivery is still ongoing. Here, we constructed AdCLD-CoV19 that could modulate humoral immunity by harboring SARS-CoV-2 antigens onto a chimeric adenovirus 5/35 platform that was effective in cellular immunity. By replacing the S1/S2 furin cleavage sequence of the SARS-CoV-2 Spike (S) protein mounted on AdCLD-CoV19 with the linker sequence, high antigen expression was confirmed in various cell lines. The high levels of antigen expression contributed to antigen-specific antibody activity in mice and non-human primates (NHPs) with a single vaccination of AdCLD-CoV19. Furthermore, the adenovirus-induced Th1 immune response was specifically raised for the S protein, and these immune responses protected the NHP against live viruses. While AdCLD-CoV19 maintained neutralizing antibody activity against various SARS-CoV-2 variants, it was reduced to single vaccination for β and ο variants, and the reduced neutralizing antibody activity was restored with booster shots. Hence, AdCLD-CoV19 can prevent SARS-CoV-2 with a single vaccination, and the new vaccine administration strategy that responds to various variants can maintain the efficacy of the vaccine

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis.

New prophylactic and therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of extensively-drug resistant form of the disease. During the course of a high-content chemical screen, ImidazoPyridine Amides (IPA) were identified as a promising class of anti-tubercular agents. The optimized IPA compound Q203 inhibits the growth of multi- and extensively-drug resistant clinical isolates of M. tuberculosis in the low nanomolar range. Q203 was efficacious in vivo at a dose below 1mg/kg, making this compound one of the most potent discovered up to date. In addition, it shows pharmacokinetic and safety profiles compatible with once daily dosing. A reverse genetic approach identifies the ubiquinol cytochrome C reductase (QcrB, Rv2196) as the target of Q203. Mode of action studies revealed that Q203 inhibits the process of ATP synthesis in both replicating and hypoxic non-replicating M. tuberculosis. Altogether, our data indicates that Q203 is a promising clinical candidate for the treatment of tuberculosis

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis, several of which are currently in clinical trials. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe