Single-Photon Level Dispersive Fourier Transform: Ultrasensitive Characterization of Noise-Driven Nonlinear Dynamics.

Dispersive Fourier transform is a characterization technique that allows directly extracting an optical spectrum from a time domain signal, thus providing access to real-time characterization of the signal spectrum. However, these techniques suffer from sensitivity and dynamic range limitations, hampering their use for special applications in, e.g., high-contrast characterizations and sensing. Here, we report on a novel approach to dispersive Fourier transform-based characterization using single-photon detectors. In particular, we experimentally develop this approach by leveraging mutual information analysis for signal processing and hold a performance comparison with standard dispersive Fourier transform detection and statistical tools. We apply the comparison to the analysis of noise-driven nonlinear dynamics arising from well-known modulation instability processes. We demonstrate that with this dispersive Fourier transform approach, mutual information metrics allow for successfully gaining insight into the fluctuations associated with modulation instability-induced spectral broadening, providing qualitatively similar signatures compared to ultrafast photodetector-based dispersive Fourier transform but with improved signal quality and spectral resolution (down to 53 pm). The technique presents an intrinsically unlimited dynamic range and is extremely sensitive, with a sensitivity reaching below the femtowatt (typically 4 orders of magnitude better than ultrafast dispersive Fourier transform detection). We show that this method can not only be implemented to gain insight into noise-driven (spontaneous) frequency conversion processes but also be leveraged to characterize incoherent dynamics seeded by weak coherent optical fields.

Photonic molecule state transition by collision.

We investigate the impact of collisions with two-frequency photonic molecules aiming to observe internal dynamic behavior and challenge their strong robustness. Versatile interaction scenarios show intriguing state changes expressed through modifications of the resulting state such as temporal compression and unknown collision-induced spectral tunneling. These processes show potential for efficient coherent supercontinuum generation and all-optical manipulation.

Host-Assisted Delivery of a Model Drug to Genomic DNA: Key Information from Ultrafast Spectroscopy and in silico Study.

Drug delivery to a target without adverse effects is one of the major criteria for clinical use. Herein, we have made an attempt to explore the delivery efficacy of SDS surfactant in a monomer and micellar stage during the delivery of the model drug, Toluidine Blue (TB) from the micellar cavity to DNA. Molecular recognition of pre-micellar SDS encapsulated TB with DNA occurs at a rate constant of k1 ∼652 s-1 . However, no significant release of encapsulated TB at micellar concentration was observed within the experimental time frame. This originated from the higher binding affinity of TB towards the nano-cavity of SDS at micellar concentration which does not allow the delivery of TB from the nano-cavity of SDS micelles to DNA. Thus, molecular recognition controls the extent of DNA recognition by TB which in turn modulates the rate of delivery of TB from SDS in a concentration-dependent manner.

In vitro and Microbiological Assay of Functionalized Hybrid Nanomaterials To Validate Their Efficacy in Nanotheranostics: A Combined Spectroscopic and Computational Study.

Functionalized nanoparticles reveal new frontiers in therapeutics and diagnostics, simultaneously referred to as theranostics. Functionalization of an inorganic nanoparticle (NP) with an organic ligand determines the interaction of the functionalized NPs with various cellular components, leading to the desired therapeutic effect, while diminishing adverse side effects. Apart from the therapeutic effect of the nanoparticles, other physical properties of the organic-inorganic complex (nanohybrid) including fluorescence, X-ray or MRI contrast offer diagnosis of the anomalous target cell. In this study we functionalized Mn3 O4 NPs with organic citrate (C-Mn3 O4 ) and folic acid (FA-Mn3 O4 ) ligands and investigated their antimicrobial activities using Staphylococcus hominis as a model bacteria, which can be remediated through their membrane rupture. While high-resolution transmission microscopy (HR-TEM), XRD, DLS, absorbance and fluorescence spectroscopy were used for structural characterisation of the functionalised NPs, zeta potential measurements and temperature-dependent reactive oxygen speices (ROS) generation reveal their drug action. We used high-end density functional theory (DFT) calculations to rationalise the specificity of the drug action of the NPs. Picosecond-resolved FRET studies confirm the enhanced affinity of FA-Mn3 O4 to the bacteria relative to C-Mn3 O4 , leading to enhanced antimicrobial activity. We have shown that the functionalised nanoparticles offer significant X-ray contrast in in-vitro studies, indicating the FA-Mn3 O4 NPs to be a potential theranostic agent against bacterial infection.

Role of frequency dependence of the nonlinearity on a soliton's evolution in photonic crystal fibers.

We reveal the crucial role played by the frequency dependence of the nonlinear parameter on the evolution of femtosecond solitons inside photonic crystal fibers (PCFs). We show that the conventional approach based on the self-steepening effect is not appropriate when such fibers have two zero-dispersion wavelengths, and several higher-order nonlinear terms must be included for realistic modeling of the nonlinear phenomena in PCFs. These terms affect not only the Raman-induced wavelength shift of a soliton but also impact its shedding of dispersive radiation.

Spectroscopic Studies on the Biomolecular Recognition of Toluidine Blue: Key Information Towards Development of a Non-Contact, Non-Invasive Device for Oral Cancer Detection.

Molecular interaction of aromatic dyes with biological macromolecules are important for the development of minimally invasive disease diagnostic biotechnologies. In the present work, we have used Toluidine Blue (TB) as a model dye, which is a well-known staining agent for the diagnosis of oral cancer and have studied the interaction of various biological macromolecules (protein and DNA) with the dye at different pH. Our spectroscopic studies confirm that TB interacts with Human Serum Albumin (HSA), a model protein at very high pH conditions which is very hard to achieve physiologically. On the other hand, TB significantly interacts with the DNA at physiological pH value (7.4). Our molecular studies strengthen the understanding of the Toluidine Blue staining of cancer cells, where the relative ratio of the nucleic acids is higher than the normal intracellular content. We have also developed a non-invasive, non-contact spectroscopic technique to explore the possibility of quantitatively detecting oral cancer by exploiting the interaction of TB with DNA. We have also reported development of a prototype named "Oral-O-Scope" for the detection of Oral cancer and have carried out human studies using the prototype.

Manipulation of infrared dispersive waves in customized microstructured optical fibers for 1.7 and 2.0 µm light sources.

We demonstrate the controllable generation of infrared dispersive waves (DWs) from customized, in-house fabricated silica microstructured optical fibers (MOFs) by manipulating the location of zero dispersion wavelength (ZDW) through the structure of the fibers. The highly enriched shaping mechanism of arrested soliton in the MOFs with two ZDWs provides a technique for efficient energy transfer into the targeted eye-safe wavelengths at 1.7 and 2.0 µm by the virtue of DW formation.

Evaluation of oxidative stress and the microenvironment in oral submucous fibrosis.

BACKGROUND: Oral Submucous fibrosis (OSF) is a chronic inflammatory mucosal disease of unknown etiology. Statistics show cases of OSF which has a high rate of overall prevalence and increase the chance of malignant transformation. As we know malignant cells is situated in a very complex microenvironment with altered metabolic pathway including intermediates which participate in oxidative stress process which enhances metabolic rewiring and promotes tumor progression. This study aims to evaluate the tumor microenvironment and their role in metabolic reprogramming. METHODS: This study was conducted on the serum sample of OSF (n = 20) compared to the healthy group (n = 20) using ELISA. The serum levels of intermediate by-products of metabolic pathway and oxidative stress induced biomolecular damage products were determined. The sensitivity of results was analyzed by correlating it with markers of metabolic status (Glucose, Total cholesterol, Total protein). RESULTS: Metabolic pathway intermediates molecules like Fatty Acids (FAA), Ascorbic acid, Citrate, Oxaloacetate (OAA), levels were significantly high in the serum of OSF cases. This indicated that intermediates act as a metabolic switch that drives cells to adapt malignant transformation pathway. Markers related to oxidative DNA damage (8-hydroxy-2' -deoxyguanosine), Oxidative lipid peroxidation (8-epi-Prostaglandin F2α), and Protein carbonyl were significantly up-regulated. This significant increase in oxidative stress marker revealed the reprogramming of the metabolic pathway for fulfilling the nutritional requirement of cancer cells. A further significant correlation was observed with metabolic products confirmed altered metabolic status. CONCLUSION: Our findings could identify the differentiating intermediate pathway metabolites and oxidative damage to biomolecules that are leading to rewiring of metabolism in the OSF group. Findings described in the study can be helpful to explain further the molecular aspects that lead to the progression of OSF towards carcinogenesis.

Soliton Molecules with Two Frequencies.

We demonstrate a peculiar mechanism for the formation of bound states of light pulses of substantially different optical frequencies, in which pulses are strongly bound across a vast frequency gap. This is enabled by a propagation constant with two separate regions of anomalous dispersion. The resulting soliton compound exhibits moleculelike binding energy, vibration, and radiation and can be understood as a mutual trapping providing a striking analogy to quantum mechanics. The phenomenon constitutes an intriguing case of two light waves mutually affecting and controlling each other.

Delineating metabolic dysfunction in cellular metabolism of oral submucous fibrosis using 1H nuclear magnetic resonance spectroscopy.

OBJECTIVE: To delineate the metabolism involved in oral submucous fibrosis progression towards carcinogenesis by 1H nuclear magnetic resonance spectroscopy. METHODS: The proposed study was designed using 1H-NMR by comparing the metabolites in the serum sample of oral submucous fibrosis (n = 20) compared to the normal group (n = 20) using 1H nuclear magnetic resonance spectroscopy. Various statistical analysis like multivariate statistical analysis, Principle component analysis, Partial least squares Discriminant Analysis, Hierarchical cluster analysis was applied to analyze potential serum metabolites. RESULTS: The results generated from the principle component analysis, partial least squares discriminant analysis and hierarchical cluster analysis are sufficient to distinguish between oral submucous fibrosis group and normal group. A total of 15 significant metabolites associated with main pathways were identified, which correlated with the progression of cancer. Up-regulation of glucose metabolism-related metabolites indicated the high energy demand due to enhanced cell division rate in the oral submucous fibrosis group. A significant increase in lipid metabolism-related metabolites revealed the reprogramming of the fatty acids metabolic pathway to fulfilling the need for cell membrane formation in cancer cells. On the other hand, metabolites related to choline phosphocholine, the metabolic pathway was also altered. CONCLUSION: Our findings could identify the differentiating metabolites in the oral submucous fibrosis group. Significant alteration in metabolites in the oral submucous fibrosis group exhibited deregulation in metabolic events. The findings reported in the study can be beneficial to further explain the molecular aspects that lead to the progression of oral submucous fibrosis towards carcinogenesis.

Automatic identification of clinically relevant regions from oral tissue histological images for oral squamous cell carcinoma diagnosis.

Identification of various constituent layers such as epithelial, subepithelial, and keratin of oral mucosa and characterization of keratin pearls within keratin region as well, are the important and mandatory tasks for clinicians during the diagnosis of different stages in oral cancer (such as precancerous and cancerous). The architectural variations of epithelial layers and the presence of keratin pearls, which can be observed in microscopic images, are the key visual features in oral cancer diagnosis. The computer aided tool doing the same identification task would certainly provide crucial aid to clinicians for evaluation of histological images during diagnosis. In this paper, a two-stage approach is proposed for computing oral histology images, where 12-layered (7 × 7×3 channel patches) deep convolution neural network (CNN) are used for segmentation of constituent layers in the first stage and in the second stage the keratin pearls are detected from the segmented keratin regions using texture-based feature (Gabor filter) trained random forests. The performance of the proposed computing algorithm is tested in our developed oral cancer microscopic image database. The proposed texture-based random forest classifier has achieved 96.88% detection accuracy for detection of keratin pearls.

Serum-based diagnostic prediction of oral submucous fibrosis using FTIR spectrometry.

Oral submucous fibrosis (OSF) is found to have the highest malignant potentiality among all other pre-cancerous lesions. However, its detection prior to tissue biopsy can be challenging in clinics. Moreover, biopsy examination is invasive and painful. Hence, there is an urgent need of new technology that facilitates accurate diagnostic prediction of OSF prior to biopsy. Here, we used FTIR spectroscopy coupled with chemometric techniques to distinguish the serum metabolic signatures of OSF patients (n=30) and healthy controls (n=30). Serum biochemical analyses have been performed to further support the FTIR findings. Absorbance intensities of 45 infrared wavenumbers differed significantly between OSF and normal serum FTIR spectra representing alterations in carbohydrates, proteins, lipids and nucleic acids. Nineteen prominent significant wavenumbers (P≤0.001) at 1020, 1025, 1035, 1039, 1045, 1078, 1055, 1100, 1117, 1122, 1151, 1169, 1243, 1313, 1398, 1453, 1544, 1650 and 1725cm-1 provided excellent segregation of OSF spectra from normal using multivariate statistical techniques. These findings provided essential information on the metabolic features of blood serum of OSF patients and established that FTIR spectroscopy coupled with chemometric analysis can be potentially useful in the rapid and accurate preoperative screening/diagnosis of OSF.

Smokeless tobacco consumption impedes metabolic, cellular, apoptotic and systemic stress pattern: A study on Government employees in Kolkata, India.

Smokeless tobacco (SLT) remains a threat amongst a large population across the globe and particularly in India. The oral use of tobacco has been implicated to cause physiological stress leading to extreme toxicological challenge. The study included 47 SLT-users and 44 non-users providing a spectrum of pathophysiological, clinico-biochemical, antioxidant parameters, cell cycle progression study of PBMC and morphological changes of red blood cells (RBC). The expressions of p53, p21, Bax, Bcl-2, IL-6, TNF- α, Cox-2, iNOS were analyzed from thirteen representative SLT-users and twelve non-users. Difference in CRP, random glucose, serum cholesterol, TG, HLDL-C, LDL-C, VLDL-C, neutrophil count, monocyte count, ESR, SOD (PBMC) and TBARS (RBC membrane) were found to be statistically significant (p < 0.05) between the studied groups. The current study confers crucial insight into SLT mediated effects on systemic toxicity and stress. This has challenged the metabolic condition leading to a rise in the inflammatory status, increased apoptosis and RBC membrane damage. The above findings were substantiated with metabolic, clinical and biochemical parameters. This is possibly the first ever in-depth report and remains an invaluable document on the fatal effects of SLT.