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Consider a nonzero contraction T and a bounded operator X satisfying T X = q X T for a complex number q. There are some interesting results in the literature on q -commuting dilation and q -commutant lifting of such pair (T , X) when | q | = 1. Here we improve a few of them to the class of scalars q satisfying | q | ≤ 1 ‖ T ‖. [ABSTRACT FROM AUTHOR]

Abstract TLR9 is one of the major innate immune receptors expressed in the endosomes of pDCs and B cells in humans. Aberrant TLR9 activation is implicated in several autoimmune and metabolic disorders as well as in sepsis, making this receptor an important therapeutic target, though specific TLR9 antagonists are yet to be available for clinical use. Here we elucidate the importance of specific physiochemical properties through substitution patterns in quinazoline scaffold to achieve potent hTLR9 inhibition at < 50 nM as well as > 600 fold selectivity against hTLR7, another closely related TLR that shares downstream signaling with TLR9 but plays distinct roles in physiology and pathology. Assays were performed using hPBMC and reporter cell lines. Favorable in vitro ADME profile, pharmacokinetics as well as validation in a clinically relevant in vivo TLR9-inhibition efficacy model in mice establish these novel TLR9-antagonists as candidate therapeutic agents in relevant clinical contexts. Graphical abstract Image 1 Highlights • Substitutions in quinazoline that influence potency and specificity for hTLR9. • Favourable in vitro ADME and pharmacokinetics in rodent model. • In vivo TLR9-inhibition efficacy was investigated in a rodent model. • Development of potent TLR9 antagonist with excellent selectivity against TLR7. [ABSTRACT FROM AUTHOR]

The article considers the successful implementation of relativistic equation-of-motion coupled cluster method for the electron attachment problem (EA-EOMCC) at the level of single- and double- excitation approximation. The implemented relativistic EA-EOMCC method is employed to calculate ionization potential values of alkali metal atoms (Li, Na, K, Rb, Cs, Fr) and the vertical electron affinity values of LiX (X = H, F, Cl, Br), NaY (Y = H, F, Cl) starting from their closed-shell configuration. Both four-component and exact two-component calculations are done for all the opted systems. Further, we have shown the effect of spin–orbit interaction considering the atomic systems. The results of our atomic calculations are compared with the values from the NIST database and the results are found to be very accurate (<1%). [ABSTRACT FROM AUTHOR]

[Display omitted] • The MoS 2 -MoSe 2 lateral heterostructure is semiconducting, whereas the MoS 2 -NbS 2 lateral heterostructure is metallic. • The 2D MoS 2 -MoSe 2 and MoS 2 -NbS 2 LHS can withstand massive volume change during the charging-discharging processes. • The MoS 2 -MoSe 2 and MoS 2 -NbS 2 lateral heterostructures give high Li/Na storage capacities of 518 mAh/g and 677 mAh/g, respectively. • MoS 2 -NbS 2 LHS is more advantageous over MoS 2 -MoSe 2 LHS for anodes of LIBs/SIBs. The requirement of an efficient energy storage device has become an exclusive requisite for technological and scientific innovations. In the present work, by using the 2D monolayer semiconductor-semiconductor and semiconductor-metal lateral interface structures as the model structure, we performed periodic DFT calculations to examine the possibility of 2D MoS 2 -MoSe 2 and MoS 2 -NbS 2 lateral heterostructures (LHS) as the electrodes of a battery. The MoS 2 -MoSe 2 lateral interface is a semiconductor, whereas the MoS 2 -NbS 2 lateral interface preserves metallic character. Besides, we found that Li/Na ion adsorption is more influential on the lateral heterostructure and is exothermic, with ultrafast diffusion, and is comparable to their monolayers. Meanwhile, the calculated open-circuit voltage is enormously low, like other widely investigated pristine 2D materials. The enhanced electrical conductivity, short diffusion distances, minutely low equilibrium voltage with good stability, large theoretical capacity and ultrahigh mechanical strength offered bare 2D TMDs lateral heterostructures as a potential candidate for LIBs/SIBs applications. This work broadens the possibility of applications based on 2D TMD-based semiconductor-semiconductor and semiconductor-metal lateral heterostructures. The lateral heterostructures can give an exciting new paradigm and offer exciting opportunities for potential applications in portable electronic devices. [ABSTRACT FROM AUTHOR]

Aberrant activation of the endosomal Toll-like receptor 7 (TLR7) has been implicated in myriad autoimmune diseases and is an established therapeutic target in such conditions. Development of diverse TLR7 antagonists is mainly accomplished through random screening. To correlate human TLR7 (hTLR7) antagonistic activity with the structural features in different chemotypes, we derived a hypothetical binding model based on molecular docking analysis along with molecular dynamics (MD) simulations study. The binding hypothesis revealed different pockets, grooves and a central cavity where ligand-receptor interaction with specific residues through hydrophobic and hydrogen bond interactions take place, which correlate with TLR7 antagonistic activity thus paving the way for rational design using varied chemotypes. Based on the structural insight thus gained, TLR7 antagonists with quinazoline were designed to understand the effect of engagement of these pockets as well as boundaries of the chemical space associated with them. The newly synthesized most potent hTLR7 antagonist, i.e. compound 63 , showed IC 50 value of 1.03 ± 0.05 μM and was validated by performing primary assay in human plasmacytoid dendritic cells (pDC) (IC 50 pDC: 1.42 μM). The biological validation of the synthesized molecules was performed in TLR7-reporter HEK293 cells as well as in human plasmacytoid dendritic cells (pDCs). Our study provides a rational design approach thus facilitating further development of novel small molecule hTLR7 antagonists based on different chemical scaffolds. Image 1 • hTLR7 antagonist binding hypothesis based on docking analysis of known antagonists. • Significance of engaging different pockets and grooves for hTLR7 antagonism. • MD simulation showed ligand binding stability and protein conformational change. • Newly designed ligands based on binding model showed potent hTLR7 antagonism. • Interaction pattern can correlate the structural change in molecule with the activity. [ABSTRACT FROM AUTHOR]

A commuting tuple of n operators (S 1 , ... , S n − 1 , P) defined on a Hilbert space H , for which the closed symmetrized polydisc Γ n = { (∑ i = 1 n z i , ∑ 1 ≤ i < j ≤ n z i z j , ... , ∏ i = 1 n z i) : | z i | ≤ 1 , i = 1 , ... , n } is a spectral set is called a Γ n -contraction. Also a triple of commuting operators (A , B , P) for which the closed tetrablock E ‾ is a spectral set is called an E -contraction, where E = { (x 1 , x 2 , x 3) ∈ C 3 : 1 − z x 1 − w x 2 + z w x 3 ≠ 0 ∀ z , w ∈ D ‾ }. There are several decomposition theorems for contraction operators in the literature due to Sz. Nagy, Foias, Levan, Kubrusly, Foguel and few others which reveal structural information of a contraction. In this article, we obtain analogues of six such major theorems for both Γ n -contractions and E -contractions. In each of these decomposition theorems, the underlying Hilbert space admits a unique orthogonal decomposition which is provided by the last component P. The central role in determining the structure of a Γ n -contraction or an E -contraction is played by positivity of some certain operator pencils and the existence of a unique operator tuple associated with a Γ n -contraction or an E -contraction. [ABSTRACT FROM AUTHOR]

Primary H 2 adsorption sites in a zeolitic imidazolate framework, ZIF-7, are identified using ab-initio density functional theory (DFT) based molecular dynamics annealing simulations. The simulations suggest several low energy adsorption sites. The effect of light transition metal decoration on hydrogen storage properties was studied. Our ab-intio DFT calculations illustrate that decorating the ZIF with Sc increases both the number of H 2 molecules, as well as the H 2 binding energy. The binding energy (∼25 kJ/mol per H 2 ) at 8H 2 loading in the pore, suggests that Sc-ZIFs can be potential candidates for hydrogen storage. [ABSTRACT FROM AUTHOR]

A comparative study of dipole moments, polarizabilities and hyperpolarizabilities of 16 different molecules is performed employing two completely different theoretical approaches namely, density functional theory (DFT) and coupled cluster singles and doubles (CCSD). Both methods include electron correlation. The CCSD method is more accurate but highly expensive. DFT with auxiliary density allows non-iterative solutions which is computational advantage and useful for large molecules. Dipole moments and polarizability calculations from DFT are in very good agreement with CCSD calculations. However, negative hyperpolarizability values from DFT differ significantly from their CCSD counterparts, whereas positive hyperpolarizabilities show reasonable agreement between these methodologies. [ABSTRACT FROM AUTHOR]

Abstract Remnant obtained from chemical retting of coconut fibre was found to have an exorbitant COD, BOD, TDS, sulphide content having blackish brown colour. Traditional (physico-chemical) treatment could not reduce its COD, TDS, colour substantially. Further, the traditional method was lengthy, consumed huge chemicals and time. Present paper reports a quicker, simpler, economic i.e., an industrially viable method to separate the chemicals and biomass by employing electrocoagulation (EC). The performance of EC was analyzed by keeping temperature, and pH of remnant constant, while varying current flow (100–2000 mA), time (15–90 min) and number of iron electrodes (2,4,6). Efficacy of EC was evaluated in terms of reduction in conductivity, pH, TDS, COD, TOC, colour and quantity of sludge generated from the wastewater. Six electrodes with 2000 mA current flow for 90 min were found to give noticeable reduction on COD (92.8%), TOC (56%), TDS (99%), and colour. To reduce pH, and TDS to an acceptable level, filtration with activated charcoal was attempted on recovered water from EC. Resultant water was also found to have acceptable LC 50 value for safe disposal. Carbon content (53%) in the sludge was high, contained lignin and cellulose whiskers also, as revealed from the EDX and FTIR, SEM respectively. Cost of EC ($ 0.087 USD/L) was found to be much less as compared to traditional method ($ 0.384 USD/L). Graphical abstract Image 1 Highlights • Remnant of chemical retting of coconut fibre was treated by electrocoagulation. • Optimum treatment condition is 6 electrodes, pH 7, 90 min and 2000 mA. • COD (80%), TOC (56%), TDS, darkness of colour were remarkably reduced. • Lethal concentration of 135 mg/L indicates its safer disposability. • Cost (USD/L) of electrolysis 0.087 as compared to chemical process 0.38. [ABSTRACT FROM AUTHOR]

Toll-like receptor 9 (TLR9) is a major therapeutic target for numerous inflammatory disorders. Development of small molecule inhibitors for TLR9 remains largely empirical due to lack of structural understanding of potential TLR9 antagonism by small molecules and due to the unusual topology of the ligand binding surface of the receptor. To develop a structural model for rational design of small molecule TLR9 antagonists, an enhanced homology model of human TLR9 (hTLR9) was constructed. Binding mode analysis of a series of molecules having characteristic molecular geometry, flexibility and basicity was conducted based on crystal structure of the inhibitory DNA (iDNA) bound to horse and bovine TLR9. Interaction with specific amino acid residues in four leucine rich repeat (LRR) regions of TLR9 was identified to be critical for antagonism by small molecules. The biological validation of TLR9 antagonism and its correlation with probe-receptor interactions led to a reliable model that could be used for development of novel small molecules with potent TLR9 antagonism (IC 50 30–100 nM) with excellent selectivity against TLR7. [ABSTRACT FROM AUTHOR]

Vinblastine (VLB), a cytotoxic alkaloid is used extensively against various cancer types and the crystal structure of its tubulin complex is already known. Multitarget affinity of vinblastine has been investigated and the nature of binding with biological receptors namely, duplex DNA and Human serum albumin (HSA) has been compared to the binding characteristics of its known complex with natural high affinity receptor tubulin using molecular docking and QM–MM calculations. VLB is found to interact with DNA as well as HSA protein, though, with weaker affinity as compared to tubulin. Analysis of various docked complexes revealed that the H-bonds and cation–pi bonds do not have significant contribution to the binding interactions and despite its large size, VLB remains in relaxed conformation and fits in the hydrophobic regions on the receptors. [ABSTRACT FROM AUTHOR]

We have recently reported a new chemotype of a potent topoisomerase I poison with compound 1 as a potential anticancer chemotherapeutic agent. During further optimization, it has been observed that compound 1 suffers from high intrinsic clearance in human liver microsomes. To overcome the metabolic instability of compound 1 , we report design and synthesis of metabolically stable Top1 poison 3. Newly identified Top1 poison 3 exhibits t 1/2 of 69.1 min in human liver microsomes in comparison to compound 1 with t 1/2 of 9.9 min. Molecular dynamic study of the newly optimized Top1 poison 3 was performed to get the insight into the stability of the binding pose in the active site. Compound 3 was able to trap DNA-Top1 cleavage complex and found to be less cytotoxic in non-cancerous cell line as compared to compound 1. Image 1 • Strategic development of potent Top1 poison with enhanced metabolic stability. • Validation of compound 3 as Top1 poison by ex vivo plasmid DNA cleavage assay. • Molecular Dynamic simulations of compound 3 in the active site. • Lead compound 3 found to be less cytotoxic in non-cancerous cell line. [ABSTRACT FROM AUTHOR]