Acid-catalyzed Transformation of Nitrite to Nitric Oxide on Copper(II)-Cobalt(II) Centers in a Bimetallic Complex.

Nitrite (NO2-) serves as a pool of nitric oxide (NO) in biological systems under hypoxic conditions, and it is transformed to NO by nitrite reductase (NiR) enzyme in the presence of acid. However, NO synthases generate NO in normoxic conditions. Previously, acid-induced NO2- reduction chemistry was modeled on mono-metallic 3d-metals, generating metal-nitrosyls or NO(g) with H2O or H2O2 products. Herein, to understand the relative potency of a bimetallic system, we report the acid-induced reductive conversion of η2-bound NO2- to NO on CuII-CoII centers of a hetero-bimetallic CuII­nitrito-CoII complex, [(LN8H)CuII­NO2-­CoII]3+ (CuII-NO2--CoII, 2) bearing an octadentate N8-cryptand ligand (LN8H). The CuII-NO2--CoII generates [CuII(LN8H)CoII]4+ (1) upon reaction with one equiv. acid (HClO4, H+ ions source) with NO(g) via a presumed transient nitrousacid (ONOH) intermediate species. Likewise, this NO2- reduction was found to form H2O, which is believed to be from the decomposition of H2O2, an intermediate species. In addition, complex 2, in the presence of more than one equiv. H+ ions also showed the formation of NO(g) with H2O. Mechanistic investigations, using 15N-labeled-15NO2-, 18O-labeled-18O14N16O- and 2H-labeled-DClO4 (D+ source), revealed that the N-atom and O-atom in the 14/15NO and 14N18O gases are derived from NO2- ligand and H-atom in H2O derived from H+-source, respectively.

Exceptional-point-induced asymmetric mode conversion in a dual-core optical fiber segment.

The engineering of exceptional points (EPs) in open optical systems has lately attracted much attention for developing future all-optical devices. However, investigation of the fascinating features of EPs in fiber geometries is lacking. We design a fabrication feasible dual-core optical fiber segment, where non-Hermiticity in terms of a symmetric customized gain-loss profile is introduced to modulate the interaction between two corresponding coupled modes toward hosting a dynamical EP encirclement scheme in the gain-loss parameter space. An asymmetric conversion process between two supported modes is reported by exploiting the chirality of the encountered EP. The proposed scheme can lead to an advanced platform to design mode-manipulative all-optical components in communication and all-fiber photonic devices.

On-Board Ship Detection for Medium Resolution Optical Sensors.

In recent years there has been an increased interest in ocean surveillance. The activity includes control and monitoring of illegal fisheries, manmade ocean pollution and illegal sea traffic surveillance, etc. The key problem is how to identify ships and ship-like objects accurately and in a timely manner. In this context, currently, many solutions have been proposed based on high resolution optical and radar remote sensing systems. Most often, these systems suffer from two major limitations viz., limited swath, thereby requiring multiple satellites to cover the region of interest and huge volumes of data being transmitted to ground, even though effective per-pixel information content is minimal. Another limitation is that the existing systems are either simulated on ground or built using the non-space qualified/Commercial Of-The-Shelf (COTS) components. This paper proposes an efficient on-board ship detection system/package connected with medium resolution wide swath optical camera. The methodology adopted has three major components, viz., onboard data processing for improving the radiometric fidelity, followed by a ship detection using modified Constant False Alarm Rate algorithm (CFAR) and a false alarm suppression module to mask false identifications. Finally, the package outputs only the locations of the ships, which is transmitted to the ground. The proposed system reduces the effective volume of data to be transmitted and processed on ground and also significantly cuts down the turnaround time for achieving the end objective. The system is built on radiation hardened Field Programmable Gate Array (FPGA) devices to meet the various engineering constraints such as real-time performance, limited onboard power, radiation hardness, handling of multiple custom interfaces etc. The system is tested with one of the medium resolution Multispectral Visual and Near Infra-Red (MX-VNIR) sensor having a spatial resolution of around 50 m and swath of around 500 Kms, which would be flown with one of the upcoming satellites. The systems performance is also verified on ground with Indian Remote Sensing (IRS) Satellite's Resourcesat's Advanced Wide Field Sensor (AWiFS) data and the results are found to be quite encouraging as well as meeting the mission objectives.

Chirality breakdown in the presence of multiple exceptional points and specific mode excitation.

The dynamical parametric encirclement around a second-order exceptional point (EP) enables the time-asymmetric nonadiabatic evolution of light, which follows the chirality of the underlying system. Such light dynamics in the presence of multiple EPs and the corresponding chiral aspect is yet to be explored. In this Letter, we report a gain-loss assisted four-mode-supported optical waveguide that hosts a parameter space to dynamically encircle multiple EPs. In the presence of multiple EPs, we establish a unique nonadiabatic behavior of light, where beyond the chiral aspect of the system, light is switched to a particular mode, irrespective of the choice of the input mode. Proposed scheme certainly opens a step-forward approach in light manipulation to facilitate next-generation integrated photonic systems.

Asymmetric propagation and limited wavelength translation of optical pulses through a linear dispersive time-dynamic system.

We study optical pulse propagation through a linear, dispersive, gain-loss-assisted bulk medium whose refractive index is time-varying. To analyze the dynamics, we have used a novel technique of time transformation that provides universal formulas of pulse propagation. Our analytical and numerical investigations reveal that optical pulses show asymmetric behavior while propagating in opposite direction through such a medium, in both the temporal and spectral domains. Moreover, the wavelength shift during this process is the most interesting outcome which is limited in range, but could be tuned by varying the refractive index with time. Phenomena that are observed in this Letter are novel and realizable in practical devices such as coupled waveguides where the refractive index is a function of time.

Novel 1,4-dihydropyridine induces apoptosis in human cancer cells through overexpression of Sirtuin1.

1,4-Dihydropyridines (1,4-DHPs) are important as a class of heterocyclic compounds that exhibit wide range of biological actions. Many of its derivatives are already characterized as medicinally important drugs and used worldwide. In this study, we have screened some novel Hantzsch 1,4-DHP compounds using both in silico (QSAR and Pharmacophore) and in vitro (cytotoxic screening). 1,4-DHP showed selective cytotoxicity against five human cancerous cell lines; A375, A549, HeLa, HepG2 and SH-SY5Y but limited effect towards normal skin keratinocyte (HaCaT), lung fibroblast (WL-38) and healthy peripheral blood mononuclear cells. In A375 and HepG2 cells, one of the 1,4-DHP derivative (DHP-8) was found to inhibit cell proliferation, and simultaneously increased the apoptotic population as well as mitochondrial membrane depolarization. Furthermore, the mitochondrial signal was triggered with the activation of cleaved Caspase9, Caspase3 and PARP. The treatment with DHP-8 also increased the expression level of SIRT1, subsequently decreasing the level of pAKTser473 and survivin. Reduced pAKTser473 expression led to decrease the phosphorylated inactive form of GSK3ßser9 and as a result, proteasomal degradation of Mcl-1 occurred in both the cell lines. Here, we suggest that the apoptotic effect of DHP-8 in A375 and HepG2 cells was mediated by AKT and survivin pathways through SIRT1 activation. The involvement of DHP-8 in SIRT1 activation was further verified by co-treatment of nicotinamide with DHP-8 in both A375 and HepG2 cells. Overall, this study emphasizes the possible potential and therapeutic role of DHP-8 in skin and liver cancer.

Signature of phase singularities in diffusive regimes in disordered waveguide lattices: interplay and qualitative analysis.

Coexistence and interplay between mesoscopic light dynamics with singular optics in spatially disordered waveguide lattices are reported. Two CW light beams of a 1.55 µm operating wavelength are launched as inputs to 1D waveguide lattices with controllable weak disorder in a complex refractive index profile. Direct observation of phase singularities in the speckle pattern along the length is numerically demonstrated. Quantitative analysis of the onset of such singular behavior and diffusive wave propagation is analyzed for the first time, to the best of our knowledge.

Propagation and asymmetric behavior of optical pulses through time-dynamic loss-gain-assisted media.

We report an asymmetric behavior of optical pulses during their propagation through a time-varying linear optical medium. The refractive index of the medium is considered to be varying with time and complex, such that a sufficient amount of gain and loss is present to realize their effect on pulse propagation. We have exploited the universal formula for optical fields in time-varying media. Numerically simulated results reveal that pulses undergo opposite temporal shifts around their initial center position during their bi-directional propagation through the medium along with corresponding spectral shifts. Moreover, the peak power and accumulated chirp (time derivative of accumulated phase) of the output pulse in both propagation directions are also opposite in nature, irrespective of their initial state. Numerically simulated behavior of the pulses agrees well with the analytical solutions.

Nitric Oxide Reactivity of a Cu(II) Complex of an Imidazole-Based Ligand: Aromatic C-Nitrosation Followed by the Formation of N-Nitrosohydroxylaminato Complex.

A binuclear Cu(II) complex, 1, [Cu2(L-)2(OAc)](OAc) of imidazole-based ligand LH {LH = 2-(bis(2-ethyl-5-methyl-1H-imidazol-4-yl)methyl)phenol} was synthesized and characterized spectroscopically and structurally. Addition of an equivalent amount of nitric oxide (NO) by a gastight syringe to the acetonitrile:methanol (5:1, v/v) solution of complex 1 at room temperature resulted in the reduction of Cu(II) center to Cu(I) with concomitant C-nitrosation of the ligand. Spectroscopic characterization of the resulting Cu(I) complex (1a) of the C-nitrosylated ligand, L' {L' = 2-(bis(2-ethyl-5-methyl-1H-imidazol-4-yl)methyl)-4-nitroso-phenol} has been done. The Cu(I) complex, 1a, further reacted with NO to result in the corresponding N-nitrosohydroxylaminato complex, 2, [Cu2(L-ONNO)2](OAc)2 through the formation of a Cu(I)-nitrosyl intermediate. A small fraction of the nitrosyl intermediate decomposed to the corresponding Cu(II) complex 3, [Cu(L')2], and N2O in a parallel reaction.

Reaction of a Co(III)-Peroxo Complex and NO: Formation of a Putative Peroxynitrite Intermediate.

A Co(II) complex, [Co(L)2]Cl2, 1 of the ligand L (L = bis(2-ethyl-4-methylimidazol-5-yl)methane) upon reaction with H2O2 in methanol solution at -40 °C resulted in the formation of the corresponding Co(III)-peroxo complex [Co(L)2(O2)]+ (2). The addition of NO gas to the freshly generated solution of the complex 2 led to the formation of the Co(II)-nitrato complex 3 through the putative formation of a Co(II)-peroxynitrite intermediate, 2a. The intermediate 2a was found to mediate the nitration of the externally added phenol resembling the nitration of tyrosine in biological systems.

Dioxygenation Reaction of a Cobalt-Nitrosyl: Putative Formation of a Cobalt-Peroxynitrite via a {CoIII(NO)(O2-)} Intermediate.

A cobalt-nitrosyl complex, [(BPI)Co(NO)(OAc)], 1 {BPI = 1,3-bis(2'-pyridylimino)isoindol} was prepared and characterized. Structural characterization revealed that the cobalt center has a distorted square pyramidal geometry with the NO group coordinated from the apical position in a bent fashion. The addition of dioxygen (O2) to the dichloromethane solution of complex 1 resulted in the formation of nitro complex, [(BPI)Co(NO2)(OAc)], 2. It was characterized structurally. Kinetic studies suggested the involvement of an associative mechanism. FT-IR spectroscopic studies suggested the formation of the intermediate 1a [(BPI)CoIII(NO)(O2-)(OAc)] in the reaction. The intermediate 1a decomposed to complex 2 via a presumed peroxynitrite intermediate which was implicated by its characteristic phenol ring nitration reaction.

Reaction of a Nitrosyl Complex of Cobalt Porphyrin with Hydrogen Peroxide: Putative Formation of Peroxynitrite Intermediate.

The cobalt porphyrin complex [(Cl4TPP)Co], 1, {Cl4TPP = 5,10,15,20-tetrakis(4'-chlorophenyl)porphyrinate dianion} in dichloromethane solution was subjected to react with nitric oxide (NO) gas and resulted in the formation of the corresponding nitrosyl complex [(Cl4TPP)Co(NO)], 2, having {CoNO}8 description. It was characterized by spectroscopic studies and single-crystal X-ray structure determination. It did not react with dioxygen. However, in CH2Cl2/CH3CN solution, it reacted with H2O2 to result in the Co-nitrito complex [(Cl4TPP)Co(NO2)], 3, with the simultaneous release of O2. It induced ring nitration to the added phenol in an appreciable yield. The reaction presumably proceeds through the formation of corresponding Co-peroxynitrite intermediate.

DNA polymerase ß deficiency leads to neurodegeneration and exacerbates Alzheimer disease phenotypes.

We explore the role of DNA damage processing in the progression of cognitive decline by creating a new mouse model. The new model is a cross of a common Alzheimer's disease (AD) mouse (3xTgAD), with a mouse that is heterozygous for the critical DNA base excision repair enzyme, DNA polymerase ß. A reduction of this enzyme causes neurodegeneration and aggravates the AD features of the 3xTgAD mouse, inducing neuronal dysfunction, cell death and impairing memory and synaptic plasticity. Transcriptional profiling revealed remarkable similarities in gene expression alterations in brain tissue of human AD patients and 3xTg/Polß(+/-) mice including abnormalities suggestive of impaired cellular bioenergetics. Our findings demonstrate that a modest decrement in base excision repair capacity can render the brain more vulnerable to AD-related molecular and cellular alterations.

Corneal Cell Morphology in Keratoconus: A Confocal Microscopic Observation.

PURPOSE: To evaluate corneal cell morphology in patients with keratoconus using an in vivo slit scanning confocal microscope. METHODS: A cross-sectional study was conducted to evaluate the corneal cell morphology of 47 keratoconus patients and 32 healthy eyes without any ocular disease. New keratoconus patients with different disease severities and without any other ocular co-morbidity were recruited from the ophthalmology department of a public hospital in Malaysia from June 2013 to May 2014. Corneal cell morphology was evaluated using an in vivo slit-scanning confocal microscope. Qualitative and quantitative data were analysed using a grading scale and the Nidek Advanced Visual Information System software, respectively. RESULTS: The corneal cell morphology of patients with keratoconus was significantly different from that of healthy eyes except in endothelial cell density (P = 0.072). In the keratoconus group, increased level of stromal haze, alterations such as the elongation of keratocyte nuclei and clustering of cells at the anterior stroma, and dark bands in the posterior stroma were observed with increased severity of the disease. The mean anterior and posterior stromal keratocyte densities and cell areas among the different stages of keratoconus were significantly different (P < 0.001 and P = 0.044, respectively). However, the changes observed in the endothelium were not significantly different (P > 0.05) among the three stages of keratoconus. CONCLUSION: Confocal microscopy observation showed significant changes in corneal cell morphology in keratoconic cornea from normal healthy cornea. Analysis also showed significant changes in different severities of keratoconus. Understanding the corneal cell morphology changes in keratoconus may help in the long-term monitoring and management of keratoconus.

Suppression of excess noise of longer-lived high-quality states in nonuniformly pumped optical microcavities.

We study the formation of longer-lived states via internal coupling near a special avoided resonance crossing between the interacting states in an open optical system. Away from the parity-time symmetry limit, we discuss unconventional cavity resonance states created by a spatially varying gain/loss profile. Now, via S-matrix formalism, we have numerically demonstrated that with suitably chosen system openness and coupling strengths, the excess noise generation among the interacting nonorthogonal states (calculated as Petermann factor K) can be suppressed close to the ideal value of one with a simultaneous order of magnitude enhancement in the quality-factor of the longer-lived state.

Comparative Analysis of Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Multicentric Observational Study from Eastern India.

BACKGROUND: Tenecteplase is used as an alternative to alteplase and is considered noninferior for thrombolysis in acute ischemic stroke. OBJECTIVES: To compare the effectiveness and adverse effects of tenecteplase and alteplase in the real-world management of acute ischemic stroke. MATERIALS AND METHODS: In this retrospective observational study, we collected data from acute ischemic stroke patients admitted in six hospitals in West Bengal, India, and were thrombolysed with tenecteplase or alteplase between July 2021 and June 2022. Demographic data, baseline parameters, hospital course, and 3-month follow-up data were collected. The percentage of patients achieving a score of 0-2 in the modified Ranking scale at 3 months, rate of symptomatic intracranial hemorrhage, and all-cause mortality within 3 months were the main parameters of comparison between the two thrombolytic agents. RESULTS: A total of 162 patients were initially included in this study. Eight patients were excluded due to unavailability of follow-up data. Among the remaining patients, 71 patients received tenecteplase and 83 patients received alteplase. There was no statistically significant difference between tenecteplase and alteplase with respect to the percentage of patients achieving functional independence (modified Rankin scale score 0-2) at 3 months (53.5% vs. 60.2%, P = 0.706), rate of symptomatic intracranial hemorrhage (5.6% vs. 10.8%, P = 0.246), and all-cause mortality at 3 months (11.3% vs. 15.7%, P = 0.628). CONCLUSION: The effectiveness of tenecteplase is comparable to alteplase in the real-world management of acute ischemic stroke. Symptomatic intracranial hemorrhage and all-cause mortality rates are also similar in real-world practice.

1.5 V battery driven reduced graphene oxide-silver nanostructure coated carbon foam (rGO-Ag-CF) for the purification of drinking water.

A porous carbon foam (CF) electrode modified with a reduced graphene oxide-Ag (rGO-Ag) nanocomposite has been fabricated to purify water. It can perform as an antibacterial device by killing pathogenic microbes with the aid of a 1.5 V battery, with very little power consumption. The device is recycled ten times with good performance for long term usage. It is shown that the device may be implemented as a fast water purifier to deactivate the pathogens in drinking water.

Optimisation of an asymmetric polymerase chain reaction assay for the amplification of single-stranded DNA from Wuchereria bancrofti for electrochemical detection.

Single-stranded DNA (ssDNA) is a prerequisite for electrochemical sensor-based detection of parasite DNA and other diagnostic applications. To achieve this detection, an asymmetric polymerase chain reaction method was optimised. This method facilitates amplification of ssDNA from the human lymphatic filarial parasite Wuchereria bancrofti. This procedure produced ssDNA fragments of 188 bp in a single step when primer pairs (forward and reverse) were used at a 100:1 molar ratio in the presence of double-stranded template DNA. The ssDNA thus produced was suitable for immobilisation as probe onto the surface of an Indium tin oxide electrode and hybridisation in a system for sequence-specific electrochemical detection of W. bancrofti. The hybridisation of the ssDNA probe and target ssDNA led to considerable decreases in both the anodic and the cathodic currents of the system's redox couple compared with the unhybridised DNA and could be detected via cyclic voltammetry. This method is reproducible and avoids many of the difficulties encountered by conventional methods of filarial parasite DNA detection; thus, it has potential in xenomonitoring.

Acid-induced nitrite reduction of nonheme iron(ii)-nitrite: mimicking biological Fe-NiR reactions.

Nitrite reductase (NiR) catalyzes nitrite (NO2 -) to nitric oxide (NO) transformation in the presence of an acid (H+ ions/pH) and serves as a critical step in NO biosynthesis. In addition to the NiR enzyme, NO synthases (NOSs) participate in NO production. The chemistry involved in the catalytic reduction of NO2 -, in the presence of H+, generates NO with a H2O molecule utilizing two H+ + one electron from cytochromes and is believed to be affected by the pH. Here, to understand the effect of H+ ions on NO2 - reduction, we report the acid-induced NO2 - reduction chemistry of a nonheme FeII-nitrito complex, [(12TMC)FeII(NO2 -)]+ (FeII-NO2 -, 2), with variable amounts of H+. FeII-NO2 - upon reaction with one-equiv. of acid (H+) generates [(12TMC)Fe(NO)]2+, {FeNO}7 (3) with H2O2 rather than H2O. However, the amount of H2O2 decreases with increasing equivalents of H+ and entirely disappears when H+ reaches ≅ two-equiv. and shows H2O formation. Furthermore, we have spectroscopically characterized and followed the formation of H2O2 (H+ = one-equiv.) and H2O (H+ ≅ two-equiv.) and explained why bio-driven NiR reactions end with NO and H2O. Mechanistic investigations, using 15N-labeled-15NO2 - and 2H-labeled-CF3SO3D (D+ source), revealed that the N atom in the {Fe14/15NO}7 is derived from the NO2 - ligand and the H atom in H2O or H2O2 is derived from the H+ source, respectively.

Exploring the nitric oxide dioxygenation (NOD) reactions of manganese-peroxo complexes.

Here, we report the nitric oxide dioxygenation (NOD) reactions of two MnIII-peroxo (MIII-O22-) complexes, [(3PYENMe)MnIII(O22-)]+ (1) and [(N3PY)MnIII(O22-)]+ (2), bearing pentadentate ligands. Complexes 1 and 2 give MnII-nitrate (MnII-NO3-) complexes (3 and 4) when reacted with nitric oxide (NO), respectively. The mechanistic study explored by using 2,4-di-tert-butylphenol (2,4-DTBP) suggested that the NOD reaction of 1 and 2 occurs via a presumed Mn-peroxynitrite ([Mn-PN]+, [Mn-ONOO-]+) intermediate. Tracking the source of N atoms using 15NO revealed that the N-atoms in MnII-NO3- (3 and 4) are derived from the 15NO moiety. Furthermore, we have explored the MIII-O22- regeneration from NOD products (3 and 4), and we have observed the formation of MIII-O22- complexes (1 and 2) upon treatment with KO2 or H2O2/triethylamine (TEA), respectively.