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One of the promising technologies for isolating carbon dioxide from a mixture of industrial flue gases is the calcium looping process. This process involves a reversible reaction between sorbent Calcium Oxide and Carbon Dioxide. Because sorbent loses its activity after multiple cycles, hydration step was proposed, which is another reversible reaction where deactivated sorbent is treated with steam to form Ca(OH)2, which undergoes the backward reaction to give back the regenerated sorbent. Blamey et al. (2016) developed a shrinking core model based on which, studies were carried out on a small experimental reactor. This paper aims at developing a hybrid model by combining first principles model and an ANN model for improved prediction of the conversion in hydration of calcium looping process and to scale it up for optimal operations. The hybrid model is tested for various combinations of training variables and data sets with respect to temperature and cycle number and it is found that the hybrid model indeed gives better results. The performance prediction of Hybrid modelling is compared to the individual performance prediction of the ANN model and First principles approach.

Background Treatment failure and resistance to the commonly used drugs remains a major obstacle for successful chemotherapy against visceral leishmaniasis (VL). Since the development of novel therapeutics involves exorbitant costs, the effectiveness of the currently available antitrypanosomatid drug suramin has been investigated as an antileishmanial, specifically for VL,in vitro and in animal model experiments. Methodology/Principal Leishmania donovani promastigotes were treated with suramin and studies were performed to determine the extent and mode of cell mortality, cell cycle arrest and other in vitro parameters. In addition, L. donovani infected BALB/c mice were administered suramin and a host of immunological parameters determined to estimate the antileishmanial potency of the drug. Finally, isothermal titration calorimetry (ITC) and enzymatic assays were used to probe the interaction of the drug with one of its putative targets namely parasitic phosphoglycerate kinase (LmPGK). Findings The in vitro studies revealed the potential efficacy of suramin against the Leishmania parasite. This observation was further substantiated in the in vivo murine model, which demonstrated that upon suramin administration, the Leishmania infected BALB/c mice were able to reduce the parasitic burden and also generate the host protective immunological responses. ITC and enzyme assays confirmed the binding and consequent inhibition of LmPGK due to the drug. Conclusions/Significance All experiments affirmed the efficacy of suramin against L. donovani infection, which could possibly lead to its inclusion in the repertoire of drugs against VL., Author summary Visceral Leishmaniasis (VL) or Kala-azar, classed as a neglected tropical disease, is still a major problem worldwide, aggravated by increasing parasitic resistance against the drugs commonly used for its treatment. Since the development of novel therapeutics involves exorbitant costs, the effectiveness of the currently available antitrypanosomatid drug suramin has been investigated as an antileishmanial, specifically for VL, in vitro and in animal model experiments. Our study showed that suramin is effective against L.donovani and significantly reduced the (splenic/hepatic) parasitic burden in L. donovani infected BALB/c mice, switching the immune response in the infected BALB/c mice from TH2 to a TH1 type. The ITC data confirmed that suramin does indeed interact with parasitic phosphoglycerate kinase (LmPGK) and enzyme assays demonstrated the inhibition of LmPGK due to the drug. Therefore, our investigation raises the possibility of suramin being included in the repertoire of drugs used to treat VL.

Organic-inorganic nanohybrids are becoming popular for their potential biological applications, including diagnosis and treatment of cancerous cells. The motive of this study is to synthesise a nanohybrid for the diagnosis and therapy of colorectal cancer. Here we have developed a facile and cost-effective synthesis of folic acid (FA) templated Fe

Appropriate localization of a drug and its structure/functional integrity in a delivery agent essentially dictates the efficacy of the vehicle and the medicinal activity of the drug. In the case of a phototherapeutic drug, its photoinduced dynamics becomes an added parameter. Here, we have explored the photoinduced dynamical events of a model phototherapeutic drug psoralen (PSO) in a potential delivery vehicle called an ethosome. Dynamic light scattering confirms the structural integrity of the ethosome vehicle after the encapsulation of PSO. Steady state and picosecond resolved polarization gated spectroscopy, including the well-known strategy of solvation and Förster resonance energy transfer, reveal the localization of the drug in the vehicle and the environment in the proximity of PSO. We have also investigated the efficacy of drug delivery to various individual bacteria (Gram-negative: Escherichia coli; Gram-positive: Staphylococcus aureus) and bacterial biofilms. Our optical and electron microscopic studies reveal a significant reduction in bacterial survival (∼70%) and the destruction of bacterial adherence following a change in the morphology of the biofilms after phototherapy. Our studies are expected to find relevance in the formulation of drug delivery agents in several skin diseases and biofilm formation in artificial implants.

Organic-inorganic nanohybrids are becoming popular for their potential biological applications, including diagnosis and treatment of cancerous cells. The motive of this study is to synthesise a nanohybrid for the diagnosis and therapy of colorectal cancer. Here we have developed a facile and cost-effective synthesis of folic acid (FA) templated Fe2O3 nanoparticles with excellent colloidal stability in water using a hydrothermal method for the theranostics applications. The attachment of FA to Fe2O3 was confirmed using various spectroscopic techniques including FTIR and picosecond resolved fluorescence studies. The nanohybrid (FA-Fe2O3) is a combination of two nontoxic ingredients FA and Fe2O3, showing remarkable photodynamic therapeutic (PDT) activity in human colorectal carcinoma cell lines (HCT 116) via generation of intracellular ROS. The light induced enhanced ROS activity of the nanohybrid causes significant nuclear DNA damage, as confirmed from the comet assay. Assessment of p53, Bax, Bcl2, cytochrome c (cyt c) protein expression and caspase 9/3 activity provides vivid evidence for cell death via an apoptotic pathway. In vitro magnetic resonance imaging (MRI) experiments in folate receptor (FR) overexpressed cancer cells (HCT 116) and FR deficient human embryonic kidney cells (HEK 293) reveal the target specificity of the nanohybrid towards cancer cells, and are thus pronounced MRI contrasting agents for the diagnosis of colorectal cancer.

The jam-packed intracellular environments differ the activity of a biological macromolecule from that in laboratory environments (in vitro) through a number of mechanisms called molecular crowding related to structure, function and dynamics of the macromolecule. Here, we have explored the structure, function and dynamics of a model enzyme protein DNase I in molecular crowing of polyethylene glycol (PEG; MW 3350). We have used steady state and picosecond resolved dynamics of a well-known intercalator ethidium bromide (EB) in a 20-mer double-stranded DNA (dsDNA) to monitor the DNA-cleavage by the enzyme in absence and presence PEG. We have also labelled the enzyme by a well-known fluorescent probe 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANS) to study the molecular mechanism of the protein-DNA association through exited state relaxation of the probe in absence (dictated by polarity) and presence of EB in the DNA (dictated by Forster resonance energy transfer (FRET)). The overall and local structures of the protein in presence of PEG have been followed by circular dichroism and time resolved polarization gated spectroscopy respectively. The enhanced dynamical flexibility of protein in presence of PEG as revealed from excited state lifetime and polarization gated anisotropy of ANS has been correlated with the stronger DNA-binding for the higher nuclease activity. We have also used conventional experimental strategy of agarose gel electrophoresis to monitor DNA-cleavage and found consistent results of enhanced nuclease activities both on synthetic 20-mer oligonucleotide and long genomic DNA from calf thymus.

Chromomycin A3 (CHR, pKa = 7.0), an aureolic acid group of antitumor antibiotic, undergoes self-association in aqueous solution in neutral and anionic forms. Self-association processes of neutral and anionic CHR have been studied in pH 5.0 and pH 9.0, respectively using different spectroscopic methods such as absorbance, fluorescence, CD, NMR and isothermal titration calorimetry (ITC). Results from these studies reveal that at low concentration (2 + CHR (CHR)3 and (CHR)3 + CHR (CHR)4. Analysis of NMR spectra of 100 μM and 1 mM CHR indicates that the self-association of CHR (neutral and anionic form) is most likely to happen via hydrophobic interaction involving the sugar moieties and surrounding water molecules. Calorimetric studies indicate that self-association of both anionic and neutral CHR is entropy driven. These observations imply that sugar substituents play a major role in their state of aggregation after biosynthesis from a gene cluster. The self-association features of the antibiotic have been compared with those of Mithramycin, an antibiotic of the same group.

The structural-functional regulation of enzymes by the administration of an external stimulus such as light could create photo-switches that exhibit unique biotechnological applications. However, molecular recognition of small ligands is a central phenomenon involved in all biological processes. We demonstrate herein that the molecular recognition of a photochromic ligand, dihydroindolizine (DHI), by serine protease α-chymotrypsin (CHT) leads to the photo-control of enzymatic activity. We synthesized and optically characterized the photochromic DHI. Light-induced reversible pyrroline ring opening and a consequent thermal back reaction via 1,5-electrocyclization are responsible for the photochromic behavior. Furthermore, DHI inhibits the enzymatic activity of CHT in a photo-controlled manner. Simultaneous binding of the well-known inhibitors 4-nitrophenyl anthranilate (NPA) or proflavin (PF) in the presence of DHI displays spectral overlap between the emission of CHT-NPA or CHT-PF with the respective absorption of cis or trans DHI. The results suggest an opportunity to explore the binding site of DHI using Förster resonance energy transfer (FRET). Moreover, to more specifically evaluate the DHI binding interactions, we employed molecular docking calculations, which suggested binding near the hydrophobic site of Cys-1-Cys-122 residues. Variations in the electrostatic interactions of the two conformers of DHI adopt unfavorable conformations, leading to the allosteric inhibition of enzymatic activity.

Chelerythrine (CHL), a plant alkaloid, possesses antimicrobial, anti-inflammatory, and antitumor properties. Although CHL influences several key signal transduction pathways, its ability to interact directly with nucleoprotein complex chromatin, in eukaryotic cells has so far not been looked into. Here we have demonstrated its association with hierarchically assembled chromatin components, viz. long chromatin, chromatosome, nucleosome, chromosomal DNA, and histone H3 and the consequent effect on chromatin structure. CHL was found to repress acetylation at H3K9. It is more target-specific in terms of gene expression alteration and less cytotoxic compared to its structural analog sanguinarine.

Drug sensitization with various inorganic nanoparticles (NPs) has proved to be a promising and an emergent concept in the field of nanomedicine. Rose bengal (RB), a notable photosensitizer, triggers the formation of reactive oxygen species under green-light irradiation, and consequently, it induces cytotoxicity and cell death. In the present study, the effect of photoinduced dynamics of RB upon complexation with semiconductor zinc oxide NPs is explored. To accomplish this, we successfully synthesized nanohybrids of RB with ZnO NPs with a particle size of 24 nm and optically characterized them. The uniform size and integrity of the particles were confirmed by high-resolution transmission electron microscopy. UV/Vis absorption and steady-state fluorescence studies reveal the formation of the nanohybrids. ultrafast picosecond-resolved fluorescence studies of RB-ZnO nanohybrids demonstrate an efficient electron transfer from the photoexcited drug to the semiconductor NPs. Picosecond-resolved Forster resonance energy transfer from ZnO NPs to RB unravel the proximity of the drug to the semiconductor at the molecular level. The photoinduced ROS formation was monitored using a dichlorofluorescin oxidation assay, which is a conventional oxidative stress indicator. It is observed that the ROS generation under green light illumination is greater at low concentrations of RB-ZnO nanohybrids compared with free RB. Substantial photodynamic activity of the nanohybrids in bacterial and fungal cell lines validated the in vitro toxicity results. Furthermore, the cytotoxic effect of the nanohybrids in HeLa cells, which was monitored by MTT assay, is also noteworthy.

Mithramycin (MTR), an aureolic acid group of antitumor antibiotic is used for the treatment of several types of tumors. We have reported here the association of MTR with an essential micronutrient, manganese (Mn(2+)). Spectroscopic methods have been used to characterize and understand the kinetics and mechanism of complex formation between them. MTR forms a single type of complex with Mn(2+) in the mole ratio of 2:1 [MTR: Mn(2+)] via a two step kinetic process. Circular dichroism (CD) spectroscopic study indicates that the complex [(MTR)2 Mn(2+)] has a right-handed twist conformation similar in structure with the complexes reported for Mg(2+) and Zn(2+). This conformation allows binding via minor groove of DNA with (G, C) base preference during the interaction with double-stranded B-DNA. Using absorbance, fluorescence, and CD spectroscopy we have shown that [(MTR)2 Mn(2+)] complex binds to double-stranded DNA with an apparent dissociation constant of 32 μM and binding site size of 0.2 (drug/nucleotide). It binds to chicken liver chromatin with apparent dissociation constant value 298 μM. Presence of histone proteins in chromatin inhibits the accessibility of the complex for chromosomal DNA. We have also shown that MTR binds to Mn(2+) containing metalloenzyme manganese superoxide dismutase from Escherichia coli.

Mithramycin (MTR), an aureolic acid group of antitumor antibiotic is used for the treatment of several types of tumors. We have reported here the association of MTR with an essential micronutrient, manganese (Mn2+). Spectroscopic methods have been used to characterize and understand the kinetics and mechanism of complex formation between them. MTR forms a single type of complex with Mn2+ in the mole ratio of 2:1 [MTR: Mn2+] via a two step kinetic process. Circular dichroism (CD) spectroscopic study indicates that the complex [(MTR)2 Mn2+] has a right-handed twist conformation similar in structure with the complexes reported for Mg2+ and Zn2+. This conformation allows binding via minor groove of DNA with (G, C) base preference during the interaction with double-stranded B-DNA. Using absorbance, fluorescence, and CD spectroscopy we have shown that [(MTR)2 Mn2+] complex binds to double-stranded DNA with an apparent dissociation constant of 32 μM and binding site size of 0.2 (drug/nucleotide). It binds to chicken liver chromatin with apparent dissociation constant value 298 μM. Presence of histone proteins in chromatin inhibits the accessibility of the complex for chromosomal DNA. We have also shown that MTR binds to Mn2+ containing metalloenzyme manganese superoxide dismutase from Escherichia coli.