(a) The loudness of the sound is the measure of sound energy reaching the ear per second. It depends on the amplitude of the sound waves. It is measured in decibel (dB).

(b) On the basis of loudness, sound is classified into two types:

Soft sound: It has smaller amplitude and thus this type of sound has lesser loudness.

Loud sound: It has higher amplitude and thus this type of sound has greater loudness.

(a) The air in between Anhad and speaker vibrates with the frequency of 200 Hz. Sound is a longitudinal wave, so successive compression and rarefaction is formed between Anhad and the speaker.

(b) Anhad receives sound in the right ear by the sound waves transmitted directly from the loudspeaker, and in his left ear, he receives sound from sound waves reflected from the classroom wall.

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The recognition of G-quadruplex (G4) DNA structures as important regulatory elements in biological mechanisms, and the connection between G4s and the evolvement of different diseases, has sparked interest in developing small organic molecules targeting G4s. However, such compounds often lack drug-like properties and selectivity. Here, we describe the design and synthesis of a novel class of macrocyclic bis-indole quinolines based on their non-macrocyclic lead compounds. The effects of the macrocyclization on the ability to interact with G4 DNA structures were investigated using biophysical assays and molecular dynamic simulations. Overall, this revealed compounds with potent abilities to interact with and stabilize G4 structures and a clear selectivity for both G4 DNA over dsDNA and for parallel/hybrid G4 topologies, which could be attributed to the macrocyclic structure. Moreover, we obtained knowledge about the structure-activity relationship of importance for the macrocyclic design and how structural modifications could be made to construct improved macrocyclic compounds. Thus, the macrocyclization of G4 ligands can serve as a basis for the optimization of research tools to study G4 biology and potential therapeutics targeting G4-related diseases.

The signal transducer and activator of transcription 3 (STAT3) protein is a master regulator of most key hallmarks and enablers of cancer, including cell proliferation and the response to DNA damage. G-Quadruplex (G4) structures are four-stranded noncanonical DNA structures enriched at telomeres and oncogenes' promoters. In cancer cells, stabilization of G4 DNAs leads to replication stress and DNA damage accumulation and is therefore considered a promising target for oncotherapy. Here, we designed and synthesized novel quinazoline-based compounds that simultaneously and selectively affect these two well-recognized cancer targets, G4 DNA structures and the STAT3 protein. Using a combination of in vitro assays, NMR, and molecular dynamics simulations, we show that these small, uncharged compounds not only bind to the STAT3 protein but also stabilize G4 structures. In human cultured cells, the compounds inhibit phosphorylation-dependent activation of STAT3 without affecting the antiapoptotic factor STAT1 and cause increased formation of G4 structures, as revealed by the use of a G4 DNA-specific antibody. As a result, treated cells show slower DNA replication, DNA damage checkpoint activation, and an increased apoptotic rate. Importantly, cancer cells are more sensitive to these molecules compared to noncancerous cell lines. This is the first report of a promising class of compounds that not only targets the DNA damage cancer response machinery but also simultaneously inhibits the STAT3-induced cancer cell proliferation, demonstrating a novel approach in cancer therapy.

Fractional kinetic equations (FKEs) comprising a large array of special functions have been extensively and successfully applied in specification and solving many significant problems of astrophysics and physics. In this present work, our aim is to demonstrate solutions of (FKEs) of the generalized Hurwitz-Lerch Zeta function by applying the Sumudu transform. In addition to these, solutions of (FKEs) in special conditions of generalised Hurwitz-Lerch Zeta function have been derived. 589ccfa754

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