Two stage spectrum sensing for cognitive radio

In past few decades the need for high data rate wireless communication has experienced a booming growth indicating a huge commercial potential. The growing demand of wireless devices is restricted by the spectrum access policy of radio regulatory regime. The commercial success of the unlicensed spectrum has encouraged FCC to frame policies towards more flexible and open spectrum access. Cognitive radio has emerged as a solution to the problem of low spectral occupancy and inefficient utilization of the licensed radio spectrum. It identifies the unused portions of the licensed spectrum known as spectrum holes and makes them available for unlicensed or secondary users. Spectrum sensing, an important part of cognitive radio sense the surrounding radio environment and determines the presence or absence of the licensed user in the licensed band. It helps to get an overview on the radio environment usage and in determining the spectrum holes. The two-stage spectrum sensing method utilizes the strength of both energy and cyclostationary schemes. In this the received signal first passes through the energy detection. If the signal is not detected in this stage it goes to the cyclostationary detection stage. It was observed that the two-stage spectrum sensing method outperforms both the energy detection and cyclostationary detection method. In this dissertation, two-stage detection scheme detects the presence of wireless microphone signals and a modified detection method for cyclostationary is proposed. The simulation results verify this

P2X7 in Cancer: From Molecular Mechanisms to Therapeutics

P2X7 is a transmembrane receptor expressed in multiple cell types including neurons, dendritic cells, macrophages, monocytes, B and T cells where it can drive a wide range of physiological responses from pain transduction to immune response. Upon activation by its main ligand, extracellular ATP, P2X7 can form a nonselective channel for cations to enter the cell. Prolonged activation of P2X7, via high levels of extracellular ATP over an extended time period can lead to the formation of a macropore, leading to depolarization of the plasma membrane and ultimately to cell death. Thus, dependent on its activation state, P2X7 can either drive cell survival and proliferation, or induce cell death. In cancer, P2X7 has been shown to have a broad range of functions, including playing key roles in the development and spread of tumor cells. It is therefore unsurprising that P2X7 has been reported to be upregulated in several malignancies. Critically, ATP is present at high extracellular concentrations in the tumor microenvironment (TME) compared to levels observed in normal tissues. These high levels of ATP should present a survival challenge for cancer cells, potentially leading to constitutive receptor activation, prolonged macropore formation and ultimately to cell death. Therefore, to deliver the proven advantages for P2X7 in driving tumor survival and metastatic potential, the P2X7 macropore must be tightly controlled while retaining other functions. Studies have shown that commonly expressed P2X7 splice variants, distinct SNPs and post-translational receptor modifications can impair the capacity of P2X7 to open the macropore. These receptor modifications and potentially others may ultimately protect cancer cells from the negative consequences associated with constitutive activation of P2X7. Significantly, the effects of both P2X7 agonists and antagonists in preclinical tumor models of cancer demonstrate the potential for agents modifying P2X7 function, to provide innovative cancer therapies. This review summarizes recent advances in understanding of the structure and functions of P2X7 and how these impact P2X7 roles in cancer progression. We also review potential therapeutic approaches directed against P2X7

Modulation of Autophagy and Its Effect on Intracellular Mycobacteria by Calcimycin

Calcium ionophores like Calcimycin are known for their antimicrobial activity in vitro against gram-positive bacteria and fungi but its antimycobacterial effect is in infancy. The present study was undertaken in THP-1 cells to deduce the effect of Calcimycin on internalized mycobacteria. In our study, we observed that Calcimycin is antimycobacterial in action by inducing autophagy, one of the prominent host-defence pathways. Then, we deciphered the mechanism of autophagy induction leading to the killing of intracellular microbe and observed that Calcimycin exerts its effect through purinergic receptor P2X7 (P2RX7) that controls autophagy by regulating intracellular calcium-modulated ATP release. Further, we looked at the role of immune modulators in autophagy-dependent antimycobacterial effect of Calcimycin. We found significant IL-12 mRNA expression followed by its release in Calcimycin treated cells compared to other pro- and anti-inflammatory cytokines with concomitant expression of IL-12 receptor on the treated cell surface. P2RX7 inhibitors like 1-[N, O-bis(5-Isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62) and P2RX7 siRNA abrogated IL-12 release upon Calcimycin treatment by affecting Jun N-terminal kinase (JNK) – NF-κB signalling pathway. Specific inhibitors against JNK and NF-κB molecules showed decreased IL-12 production and less autophagy in Calcimycin treated cells that lead to a spurt in intracellular mycobacterial growth. Experiment with IL-12 neutralizing antibody conclusively proved that IL-12 acts in an autocrine fashion to regulate autophagy-dependent intracellular mycobacterial growth in Calcimycin-treated cells. So, overall our study delineated the mechanistic pathway of autophagy induction by Calcimycin that may provide an attractive target for the control of mycobacterial infection, which will help in developing better therapeutic interventions against tuberculosis (TB)