Broad spectrum anti-infective properties of benzisothiazolones and the parallels in their anti-bacterial and anti-fungal effects.

Various mono- and bis-benzisothiazolone derivatives were synthesized and screened against different strains of bacteria and fungi in order to understand the effect of multiple electrophilic sulfur atoms and substitution pattern in the immediate vicinity of reactive sulfur. Staphyllococcus aureus-ATCC 7000699, MRSA and S. aureus-ATCC 29213 (Quality Control strain) were more susceptible to this class of compounds, and the most potent derivative 1.15 had MIC50 of 0.4µg/mL (cf. Gentamicin=0.78µg/mL). CLogP value, optimally in the range of 2.5-3.5, appeared to contribute more to the activity than the steric and electronic effects of groups attached at nitrogen. By and large, their anti-fungal activities also followed a similar trend with respect to the structure and CLogP values. The best potency of IC50=0.1µg/mL was shown by N-benzyl derivative (1.7) against Aspergillus fumigatus; it was also potent against Candida albicans, Cryptococcus neoformans, Sporothrix schenckii, and Candida parapsilosis with IC50 values ranging from 0.4 to 1.3µg/mL. Preliminary studies also showed that this class of compounds have the ability to target malaria parasite with IC50 values in low micromolar range, and improvement of selectivity is possible through structure optimization.

Humid thermal ratio as a tool to assess mango thrips dynamics under subtropical climatic condition.

Weather factors play an important role in occurrence of thrips on mango. Keeping this in view, the present investigation was set out to assess the thrips population dynamics using humid thermal index, based on data sets from 22 fixed plot mango orchards in and around Lucknow. Results revealed that the highest thrips population of 3.36/panicle was recorded in Kakori (Fixed plot -I) orchard, which was followed by 2.4 and 2.06 at CISH III block and Kanar (Fixed II) respectively during the year 2013, whereas corresponding values were 4.05, 3.08 and 2.50 at CISH Block III, CISH Bolck II and Allupur respectively during 2014. The frequency distribution explained that the thrips population of <2 /panicle was widely distributed with highest frequency level. The humid thermal ratio ranged from 1.44 to 2.27 and 1.20 to 2.34 during 2013 and 2014 respectively across standard meteorological weeks. The peak thrips incidence was 6.18 /panicle during 2013 and 4.67/panicle during 2014, the corresponding values of humid thermal ratio were 1.47 and 2.05 respectively. The positive correlation was found between humid thermal ratio and thrips population dynamics during 2013 (r = 0.52**) and 2014 (r = 0.72**). Pooled data showed significant and positive correlation between humid thermal ratio and thrips population. Pooled analysis had explained up to 94 per cent of variation with exponential model (Thrips population = 0.007e2.778HTR, R2 = 0.94**) and suggested that this index might be used in understanding the mango thrips population dynamics under subtropical environmental condition.

A monoclonal antibody against glycoproteins of Aspergillus fumigatus shows anti-adhesive potential.

There has been an increase in the cases of fungal resistance against many antifungal drugs and an effective alternative mode in the form of immunotherapy is being considered as new hope. The adhesion of Aspergillus fumigatus conidia to the host components is one of the prime factors to cause aspergillosis. Carbohydrate components or glycoproteins present on the cell surface play an important role in interaction of the organism to the host and leads to adhesion. Any substance which is capable of disrupting this interaction may be a vital tool for the fungal clearance and hence may protect the host from infections caused by the fungus. In this study, a murine monoclonal antibody IgM generated against the secretory antigens of A. fumigatus, was found to be specific to a common epitope containing glyco-moieties of the various proteins and exhibited anti-adhesive potential in vitro.

Gene expression patterns in the hippocampus and amygdala of endogenous depression and chronic stress models.

The etiology of depression is still poorly understood, but two major causative hypotheses have been put forth: the monoamine deficiency and the stress hypotheses of depression. We evaluate these hypotheses using animal models of endogenous depression and chronic stress. The endogenously depressed rat and its control strain were developed by bidirectional selective breeding from the Wistar-Kyoto (WKY) rat, an accepted model of major depressive disorder (MDD). The WKY More Immobile (WMI) substrain shows high immobility/despair-like behavior in the forced swim test (FST), while the control substrain, WKY Less Immobile (WLI), shows no depressive behavior in the FST. Chronic stress responses were investigated by using Brown Norway, Fischer 344, Lewis and WKY, genetically and behaviorally distinct strains of rats. Animals were either not stressed (NS) or exposed to chronic restraint stress (CRS). Genome-wide microarray analyses identified differentially expressed genes in hippocampi and amygdalae of the endogenous depression and the chronic stress models. No significant difference was observed in the expression of monoaminergic transmission-related genes in either model. Furthermore, very few genes showed overlapping changes in the WMI vs WLI and CRS vs NS comparisons, strongly suggesting divergence between endogenous depressive behavior- and chronic stress-related molecular mechanisms. Taken together, these results posit that although chronic stress may induce depressive behavior, its molecular underpinnings differ from those of endogenous depression in animals and possibly in humans, suggesting the need for different treatments. The identification of novel endogenous depression-related and chronic stress response genes suggests that unexplored molecular mechanisms could be targeted for the development of novel therapeutic agents.

Structure and stability of different triplets involving artificial nucleobases: clues for the formation of semisynthetic triple helical DNA.

A triple helical DNA can control gene expression, help in homologous recombination, induce mutations to facilitate DNA repair mechanisms, suppress oncogene formations, etc. However, the structure and function of semisynthetic triple helical DNA are not known. To understand this, various triplets formed between eight artificial nucleobases (P, Z, J, V, B, S, X, and K) and four natural DNA bases (G, C, A, and T) are studied herein by employing a reliable density functional theoretic (DFT) method. Initially, the triple helix-forming artificial nucleobases interacted with the duplex DNA containing GC and AT base pairs, and subsequently, triple helix-forming natural bases (G and C) interacted with artificial duplex DNA containing PZ, JV, BS, and XK base pairs. Among the different triplets formed in the first category, the C-JV triplet is found to be the most stable with a binding energy of about - 31 kcal/mol. Similarly, among the second category of triplets, the Z-GC and V-GC triplets are the most stable. Interestingly, Z-GC and V-GC are found to be isoenergetic with a binding energy of about - 30 kcal/mol. The C-JV, and Z-GC or V-GC triplets are about 12-14 kcal/mol more stable than the JV and GC base pairs respectively. Microsolvation of these triplets in 5 explicit water molecules further enhanced their stability by 16-21 kcal/mol. These results along with the consecutive stacking of the C-JV triplet (C-JV/C-JV) data indicate that the synthetic nucleobases can form stable semisynthetic triple helical DNA. However, consideration of a full-length DNA containing one or more semisynthetic bases or base pairs is necessary to understand the formation of semisynthetic DNA in living cells.

Complementary base pair interactions between different rare tautomers of the second-generation artificial genetic alphabets.

The functionality of a semisynthetic DNA in the biological environment will depend on the base pair nature of its complementary base pairs. To understand this, base pair interactions between complementary bases of recently proposed eight second-generation artificial nucleobases are studied herein by considering their rare tautomeric conformations and a dispersion-corrected density functional theoretic method. It is found that the binding energies of two hydrogen-bonded complementary base pairs are more negative than those of the three hydrogen-bonded base pairs. However, as the former base pairs are endothermic, the semisynthetic duplex DNA would involve the latter base pairs.

Mechanistic insights on Bi-potentiodynamic control towards atomistic synthesis of electrocatalysts for hydrogen evolution reaction.

Herein, electrochemically assisted dissolution-deposition (EADD) is utilized over a three-electrode assembly to prepare an electrocatalyst for hydrogen evolution reaction (HER). Cyclic voltammetry is performed to yield atomistic loading of platinum (Pt) over SnS2 nanostructures via Pt dissolution from the counter electrode (CE). Astonishingly, the working electrode (WE) swept at 50 mV/s is found to compel Pt CE to experience 1000-3000 mV/s. The effect of different potential scan rates at the WE have provided insight into the change in Pt dissolution and its deposition behaviour over SnS2 in three electrode assembly. However, uncontrolled overpotentials at CE in a three-electrode assembly made Pt dissolution-deposition behavior complex. Here, for the first time, we have demonstrated bi-potentiodynamic control for dissolution deposition of Pt in four-electrode assembly over Nickel (Ni) foam. The dual cyclic voltammetry is applied to achieve better control and efficiency of the EADD process, engendering it as a pragmatically versatile and scalable synthesis technique.

Novel attractive force between ions in quantum plasmas.

We report a new attractive force between ions that are shielded by degenerate electrons in quantum plasmas. Specifically, we show that the electric potential around an isolated ion has a hard core negative part that resembles the Lennard-Jones-type potential. Physically, the new electric potential is attributed to the consideration of the quantum statistical pressure and the quantum Bohm potential, as well as the electron exchange and electron correlations due to electron-1/2 spin within the framework of the quantum hydrodynamical description of quantum plasmas. The shape of the attractive potential is determined by the ratio between the Bohr radius and the Wigner-Seitz radius of degenerate electrons. The existence of the hard core negative potential will be responsible for the attraction of ions forming lattices and atoms or molecules, as well as for critical points and phase transitions in quantum plasmas at nanoscales.

Deep Transfer Learning Based Classification Model for COVID-19 Disease.

The COVID-19 infection is increasing at a rapid rate, with the availability of limited number of testing kits. Therefore, the development of COVID-19 testing kits is still an open area of research. Recently, many studies have shown that chest Computed Tomography (CT) images can be used for COVID-19 testing, as chest CT images show a bilateral change in COVID-19 infected patients. However, the classification of COVID-19 patients from chest CT images is not an easy task as predicting the bilateral change is defined as an ill-posed problem. Therefore, in this paper, a deep transfer learning technique is used to classify COVID-19 infected patients. Additionally, a top-2 smooth loss function with cost-sensitive attributes is also utilized to handle noisy and imbalanced COVID-19 dataset kind of problems. Experimental results reveal that the proposed deep transfer learning-based COVID-19 classification model provides efficient results as compared to the other supervised learning models.

Phase coexistence and a critical point in ultracold neutral plasmas.

We show the existence of the liquid-vapor phase coexistence and a critical point for strongly coupled ions in ultracold neutral (UCN) plasmas. Expressions for the free energy of UCN plasmas and an equation of state for the ions are obtained in the mean field approximation. A van der Waals-like isotherm shows the existence of a critical point in UCN plasmas. Depending on the ion temperature, the ions are shown to exist in a mixed vapor-liquid phase for a range of the ion Coulomb coupling parameter Γ(i) (defined by the ratio between the ion interaction and the ion kinetic energies), and in a strongly coupled liquid state for values of Γ(i) above this range. The estimates of critical constants show that it may be possible to observe these phenomena in the present day UCN plasmas.

Numerical investigation of the instability and nonlinear evolution of narrow-band directional ocean waves.

The instability and nonlinear evolution of directional ocean waves is investigated numerically by means of simulations of the governing kinetic equation for narrow-band surface waves. Our simulation results reveal the onset of the modulational instability for long-crested wave trains, which agrees well with recent large-scale experiments in wave basins, where it was found that narrower directional spectra lead to self-focusing of ocean waves and an enhanced probability of extreme events. We find that the modulational instability is nonlinearly saturated by a broadening of the wave spectrum, which leads to the stabilization of the water-wave system. Applications of our results to other fields of physics, such as nonlinear optics and plasma physics, are discussed.

Binding of urea and thiourea with a barbiturate derivative: experimental and theoretical approach.

A barbiturate derivative [1,5-dihydro-5-[5-pyrimidine-2,4(1H,3H)-dionyl]-2H-chromeno[2,3-d] pyrimidine-2,4(3H)-dione)] (L1) possesses functionalities complementary to amide and thioamide. Hence its binding with urea and thiourea, is monitored using UV-vis and fluorescence titrations as well as isothermal titration calorimetry (ITC) study. Theoretical studies on hydrogen-bonded complexes of L1-urea and L1-thiourea in the gas phase, aqueous, and DMSO medium are carried out using density functional theory (DFT) at the B3LYP/6-31G** level. The theoretical calculations support the experimental results.

A Noncytotoxic Temporin L Analogue with In Vivo Antibacterial and Antiendotoxin Activities and a Nonmembrane-Lytic Mode of Action.

Cytotoxic frog antimicrobial peptide Temporin L (TempL) is an attractive molecule for the design of lead antimicrobial agents due to its short size and versatile biological activities. However, noncytotoxic TempL variants with desirable biological activities have rarely been reported. TempL analogue Q3K,TempL is water-soluble and possesses a significant antiendotoxin property along with comparable cytotoxicity to TempL. A phenylalanine residue, located at the hydrophobic face of Q3K,TempL and the "d" position of its phenylalanine zipper sequence, was replaced with a cationic lysine residue. This analogue, Q3K,F8K,TempL, showed reduced hydrophobic moment and was noncytotoxic with lower antimicrobial activity. Interestingly, swapping between tryptophan at the fourth and serine at the sixth positions turned Q3K,F8K,TempL totally amphipathic as reflected by its helical wheel projection with clusters of hydrophobic and hydrophilic residues and the highest hydrophobic moment among these peptides. Surprisingly, this analogue, SW,Q3K,F8K,TempL, was as noncytotoxic as Q3K,F8K,TempL but showed augmented antimicrobial and antiendotoxin properties, comparable to that of TempL and Q3K,TempL. SW,Q3K,F8K,TempL exhibited appreciable survival of mice against P. aeruginosa infection and a lipopolysaccharide (LPS) challenge. Unlike TempL and Q3K,TempL, SW,Q3K,F8K,TempL adopted an unordered secondary structure in bacterial membrane mimetic lipid vesicles and did not permeabilize them or depolarize the bacterial membrane. Overall, the results demonstrate the design of a nontoxic TempL analogue that possesses clusters of hydrophobic and hydrophilic residues with impaired secondary structure and shows a nonmembrane-lytic mechanism and in vivo antiendotoxin and antimicrobial activities. This paradigm of design of antimicrobial peptide with clusters of hydrophobic and hydrophilic residues and high hydrophobic moment but low secondary structure could be attempted further.

Search for new pharmacophores for antimalarial activity. Part I: synthesis and antimalarial activity of new 2-methyl-6-ureido-4-quinolinamides.

A total of 80 new 2-methyl-6-ureido-4-quinolinamides were synthesized and evaluated for their antimalarial activity. Several analogs elicited the antimalarial effect at MIC of 0.25 mg/mL against the chlooquine-sensitive P. falciparum strain. The IC(50) values of the active compounds were observed to be in ng/mL range and two of the analogs have better IC(50) value than the standard chloroquine. In the in vivo assay against mdr CQ resistant P. yoelii N67/P. yoelii nigeriensis, however, none of the compound showed complete suppression of parasitemia on day 7. One of the compounds displayed significant antibacterial effect against several strains of bacteria and was many-fold better than the standard drug gentamicin.

Quantum and classical dynamics of Langmuir wave packets.

The quantum Zakharov system in three spatial dimensions and an associated Lagrangian description, as well as its basic conservation laws, are derived. In the adiabatic and semiclassical cases, the quantum Zakharov system reduces to a quantum modified vector nonlinear Schrödinger (NLS) equation for the envelope electric field. The Lagrangian structure for the resulting vector NLS equation is used to investigate the time dependence of the Gaussian-shaped localized solutions, via the Rayleigh-Ritz variational method. The formal classical limit is considered in detail. The quantum corrections are shown to prevent the collapse of localized Langmuir envelope fields, in both two and three spatial dimensions. Moreover, the quantum terms can produce an oscillatory behavior of the width of the approximate Gaussian solutions. The variational method is shown to preserve the essential conservation laws of the quantum modified vector NLS equation. The possibility of laboratory tests in the next generation intense laser-solid plasma compression experiment is discussed.

Magnetization of a warm plasma by the nonstationary ponderomotive force of an electromagnetic wave.

It is shown that magnetic fields can be generated in a warm plasma by the nonstationary ponderomotive force of a large-amplitude electromagnetic wave. In the present Brief Report, we derive simple and explicit results that can be useful for understanding the origin of the magnetic fields that are produced in intense laser-plasma interaction experiments.

Pattern dynamics and spatiotemporal chaos in the quantum Zakharov equations.

The dynamical behavior of the nonlinear interaction of quantum Langmuir waves (QLWs) and quantum ion-acoustic waves (QIAWs) is studied in the one-dimensional quantum Zakharov equations. Numerical simulations of coupled QLWs and QIAWs reveal that many coherent solitary patterns can be excited and saturated via the modulational instability of unstable harmonic modes excited by a modulation wave number of monoenergetic QLWs. The evolution of such solitary patterns may undergo the states of spatially partial coherence (SPC), coexistence of temporal chaos and spatiotemporal chaos (STC), as well as STC. The SPC state is essentially due to ion-acoustic wave emission and due to quantum diffraction, while the STC is caused by the combined effects of SPC and quantum diffraction, as well as by collisions and fusions among patterns in stochastic motion. The energy in the system is strongly redistributed, which may switch on the onset of weak turbulence in dense quantum plasmas.

Numerical study of the magnetic electron drift vortex mode turbulence in a nonuniform magnetoplasma.

A simulation study of the magnetic electron drift vortex (MEDV) mode turbulence in a magnetoplasma in the presence of inhomogeneities in the plasma temperature and density, as well as in the external magnetic field, is presented. The study shows that the influence of the magnetic field inhomogeneity is to suppress streamerlike structures observed in previous simulation studies without background magnetic fields. The MEDV mode turbulence exhibits nonuniversal (non-Kolmogorov-type) spectra for different sets of the plasma parameters. In the presence of an inhomogeneous magnetic field, the spectrum changes to a 7/3 power law, which is flatter than without magnetic field gradients. The relevance of this work to laser-produced plasmas in the laboratory is briefly mentioned.

Cylindrical and spherical ion-acoustic envelope solitons in multicomponent plasmas with positrons.

The nonlinear wave modulation of planar and nonplanar (cylindrical and spherical) ion-acoustic envelope solitons in a collisionless unmagnetized electron-positron-ion plasma with two-electron temperature distributions has been studied. The reductive perturbative technique is used to obtain a modified nonlinear Schrödinger equation, which includes a damping term that accounts for the geometrical effect. The critical wave number threshold Kc, which indicates where the modulational instability sets in, has been determined for various regimes. It is found that an increase in the positron concentration (alpha) leads to a decrease in the critical wave number (Kc) until alpha approaches certain value alphac (critical positron concentration), then further increase in alpha beyond alphac increases the value of Kc. Also, it is found that there is a modulation instability period for the cylindrical and spherical wave modulation, which does not exist in the one-dimensional case.

A novel monoclonal antibody against enolase antigen of Aspergillus fumigatus protects experimental aspergillosis in mice.

Aspergillus fumigatus is one of the most common opportunistic fungal pathogens responsible for a variety of diseases in human, from allergic bronchopulmonary aspergillosis to chronic pulmonary aspergillosis, mostly in immunocompromized patients. In this study, one monoclonal antibody MAb R-5 (IgM) raised against enolase cell surface protein of A. fumigatus exhibited significant inhibition of spore germination in A. fumigatus (88.3%), Aspergillus flavus (57.4%) and Aspergillus niger (30.6%). The MAb R-5 also showed in vitro fungicidal activity against these species as follows: A. fumigatus (24.1%), A. flavus (13.3%) and A. niger (8.8%). These findings were supported by the indirect immunofluorescence microscopy, where the antibody showed binding with germinated spores and hyphae of A. fumigatus as well as A. flavus and A. niger.In vivo protective effect of MAb R-5 was evaluated in BALB/c mice challenged intravenously with A. fumigatus spores, where a significant reduction in CFU (85.9%) was observed in kidney tissue. The mean survival time of mice treated with MAb R-5 (18.5 days) was also enhanced compared to control (6.5 days). These results indicate that MAb R-5 could be valuable in diagnosis as well as in the treatment of broad range of Aspergillus infections.