Macrophage-targeted versus free calcitriol as host-directed adjunct therapy against Mycobacterium tuberculosis infection in mice is bacteriostatic and mitigates tissue pathology.

Host-directed therapy (HDT) with vitamin D in tuberculosis (TB) is beneficial only if the subject is deficient in vitamin D. We investigated pulmonary delivery of 1,25-dihydroxy vitamin D3 (calcitriol) in mice infected with Mycobacterium tuberculosis (Mtb). We made two kinds of dry powder inhalations (DPI)- soluble particles or poly(lactide) (PLA) particles. We compared treatment outcomes when infected mice were dosed with a DPI alone or as an adjunct to standard oral anti-TB therapy (ATT). Mice infected on Day 0 were treated between Days 28-56 and followed up on Days 57, 71, and 85. Neither DPI significantly reduced Mtb colony forming units (CFU) in the lungs. Combining DPI with ATT did not significantly augment bactericidal activity in the lungs, but CFU were 2-log lower in the spleen. CFU showed a rising trend on stopping treatment, sharper in groups that did not receive calcitriol. Lung morphology and histology improved markedly in animals that received PLA DPI; with or without concomitant ATT. Groups receiving soluble DPI had high mortality. DPI elicited cathelicidin, interleukin (IL)-1 and induced autophagy on days 57, 71, and 85. Macrophage-targeted calcitriol is therefore bacteriostatic, evokes innate microbicidal mechanisms, and mitigates pathology arising from the host response to Mtb.

Mycobacteriophages: therapeutic approach for mycobacterial infections.

Tuberculosis (TB) is a significant global health threat, and cases of infection with non-tuberculous mycobacteria (NTM) causing lung disease (NTM-LD) are rising. Bacteriophages and their gene products have garnered interest as potential therapeutic options for bacterial infections. Here, we have compiled information on bacteriophages and their products that can kill Mycobacterium tuberculosis or NTM. We summarize the mechanisms whereby viable phages can access macrophage-resident bacteria and not elicit immune responses, review methodologies of pharmaceutical product development containing mycobacteriophages and their gene products, mainly lysins, in the context of drug regulatory requirements and we discuss industrially relevant methods for producing pharmaceutical products comprising mycobacteriophages, emphasizing delivery of mycobacteriophages to the lungs. We conclude with an outline of some recent case studies on mycobacteriophage therapy.

Fostering the unleashing potential of nanocarriers-mediated delivery of ocular therapeutics.

Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the physiological static barriers such as the complex layers of the cornea, sclera and retina which restrict the drug from permeating into the anterior and posterior segments of the eye. Recent years have witnessed inventions in the field of conventional and nanocarrier drug delivery which have shown considerable enhancement in delivering small to large molecules across the eye. The dynamic challenges associated with conventional systems include limited drug contact time and inadequate ocular bioavailability resulting from solution drainage, tear turnover, and dilution or lacrimation. To this end, various bioactive-based nanosized carriers including liposomes, ethosomes, niosomes, dendrimer, nanogel, nanofibers, contact lenses, nanoprobes, selenium nanobells, nanosponge, polymeric micelles, silver nanoparticles, and gold nanoparticles among others have been developed to circumvent the limitations associated with the conventional dosage forms. These nanocarriers have been shown to achieve enhanced drug permeation or retention and prolong drug release in the ocular tissue due to their better tissue adherence. The surface charge and the size of nanocarriers (10-1000 nm) are the important key factors to overcome ocular barriers. Various nanocarriers have been shown to deliver active therapeutic molecules including timolol maleate, ampicillin, natamycin, voriconazole, cyclosporine A, dexamethasone, moxifloxacin, and fluconazole among others for the treatment of anterior and posterior eye diseases. Taken together, in a nutshell, this extensive review provides a comprehensive perspective on the numerous facets of ocular drug delivery with a special focus on bioactive nanocarrier-based approaches, including the difficulties and constraints involved in the fabrication of nanocarriers. This also provides the detailed invention, applications, biodistribution and safety-toxicity of nanocarriers-based therapeutcis for the ophthalmic delivery.

Atmospheric aerosol chemistry and source apportionment of PM10 using stable carbon isotopes and PMF modelling during fireworks over Hyderabad, southern India.

This study examined the influence of fireworks on atmospheric aerosols over the Southern Indian city of Hyderabad during festival of Diwali using mass closure, stable carbon isotopes and the EPA-PMF model. Identification of chemical species in day and night time aerosol samples for 2019 and 2020 Diwali weeks showed increased concentrations of NH4+, NO3-, SO42-, K+, organic carbon (OC), Ba, Pb and Li, which were considered as tracers for fireworks. PM10 source apportionment was done using inorganic (trace elements, major ions) and carbonaceous (organic and elemental carbon; OC & EC) constituents, along with stable isotopic compositions of TC and EC. K+/Na+ ∼1 and K+nss/OC > 0.5 indicated contribution from fireworks. High NO3-, NH4+, Na+, Cl- and SO42- suggested the presence of deliquescent salts NaCl, NH4NO3 and (NH4)2SO4. TAE/TCE >1 suggested H+ exclusion, indicating possible presence of H2SO4 and NH4HSO4 in the aerosols. Ba, Pb, Sb, Sr and Fe increased by 305 (87), 12 (11), 12 (3), 3 (2) and 3 (4) times on Diwali nights, compared to pre-Diwali of 2019 (2020), and are considered as metallic tracers of fireworks. δ13CTC and δ13CEC in aerosols closely resembled that of diesel and C3 plant burning emissions, with meagre contribution from firecrackers during Diwali period. The δ13CEC was relatively depleted than δ13CTC and δ13COC. For both years, δ13COC-EC (δ13COC - δ13CEC) were positive, suggesting photochemical aging of aerosols during long-range transport, while for pre-Diwali 2019 and post-Diwali 2020, δ13COC-EC were negative with high OC/EC ratio, implying secondary organic aerosols formation. High toluene during Diwali week contributed to fresh SOA formation, which reacted with precursor 12C, leading to 13C depletions. Eight-factored EPA-PMF source apportionment indicated highest contribution from residue/waste burning, followed by marine/dust soil and fireworks, while least was contributed from solid fuel/coal combustion.

A Quality by Design Approach for Developing SNEDDS Loaded with Vemurafenib for Enhanced Oral Bioavailability.

Vemurafenib (VMF) is a practically insoluble (< 0.1 µg/mL) and least bioavailable (1%) drug. To enhance its oral bioavailability and solubility, we formulated a reliable self-nano emulsifying drug delivery system (SNEDDS). A Quality by Design (QbD) approach was used to optimize the ratio of Capryol 90, Tween 80, and Transcutol HP. VMF-loaded SNEDDS was characterized for its size, polydispersity index (PDI), zeta potential, drug content, and transmittance. The in vitro release profile of the drug loaded in SNEDDS was compared to the free drug in two media, pH 6.8 and 1.2, and the data obtained were analyzed with different mathematical models. A reverse-phase ultra-pressure liquid chromatography (UPLC) technique with high sensitivity and selectivity was developed and validated for the quantification of VMF in analytical and bioanalytical samples. Dissolution efficiency for SNEDDS was estimated using different models, which proved that the developed novel SNEDDS formulation had a better in vitro dissolution profile than the free drug. A 2.13-fold enhanced oral bioavailability of VMF-loaded SNEDDS compared to the free drug demonstrates the superiority of the developed formulation. This work thus presents an overview of VMF-loaded SNEDDS as a promising alternative to improve the oral bioavailability of the drug.

Optimizing the fabrication of electrospun nanofibers of prochlorperazine for enhanced dissolution and permeation properties.

Despite being an approved antiemetic for more than five decades, the clinical usefulness of prochlorperazine is limited by its low solubility and inconsistent absorption in the gastrointestinal tract, which presents challenges for nanotherapeutic interventions. Here, we report the preparation of a highly soluble and permeable nanofiber formulation of prochlorperazine using the Quality-by-Design approach. The final nanofiber formulation with drug entrapment of 88.02 ± 1.14 % was obtained at 20.0 kV, with a flow rate of 0.5 ml/h and tip-to-collector distance of 19.9 cm. Physio-mechanical properties, such as thickness (0.42 ± 0.02 mm), pH resistance (7.04 ± 0.08), folding endurance (54 ± 5), and tensile strength (0.244 ± 0.02 N.mm-2), were appropriate for packaging and application to oromucosal surfaces. The content uniformity (93.48-106.63 %) and weight variation (<1.8 mg) of the optimal nanofiber formulation were within the permissible limits prescribed for orodispersible films. Microscopical investigations confirm a randomly deposited and dense network of woven nanofibers with an average diameter of 363 ± 5.66 nm. The drug particles were embedded homogeneously on the fiber in the nanoform (4.27 ± 1.34 nm). The spectral analysis using TEM-EDS shows diffraction peaks of sulfur and chlorine, the elemental constituents of prochlorperazine. The drug was amorphized in the nanofiber formulation, as led by the decline of the crystallinity index from 87.25 % to 7.93 % due to electrostatic destabilization and flash evaporation of the solvent. The enthalpy of fusion values of the drug in the nanofiber mat decreased significantly to 23.6 J/g compared to its pristine form, which exhibits a value of 260.7 J/g. The nanofibers were biocompatible with oral mucosal cells, and there were no signs of mucosal irritation compared to 1 % sodium lauryl sulfate. The fiber mats rapidly disintegrated within <1 s and released ≈91.49 ± 2.1 % of the drug within 2 min, almost 2-fold compared to the commercial Stemetil MD® tablets. Similarly, the cumulative amount of the drug permeated across the unit area of the oromucosal membrane was remarkably high (31.28 ± 1.30 µg) compared to 10.17 ± 1.11 µg and 13.10 ± 1.79 µg from the cast film and drug suspension. Our results revealed these nanofiber formulations have the potential to be fast-dissolving oromucosal delivery systems, which can result in enhanced bioavailability with an early onset of action due to rapid disintegration, dissolution, and permeation.

Transcriptional regulation of suppressors of cytokine signaling during infection with Mycobacterium tuberculosis in human THP-1-derived macrophages and in mice.

Mycobacterium tuberculosis (Mtb) infection leads to upregulation of Suppressors of Cytokine signaling (SOCS) expression in host macrophages (Mϕ). SOCS proteins inhibit cytokine signaling by negatively regulating JAK/STAT. We investigated this host-pathogen dialectic at the level of transcription. We used phorbol-differentiated THP-1 Mϕ infected with Mtb to investigate preferential upregulation of some SOCS isoforms that are known to inhibit signaling by IFN-γ, IL-12, and IL-6. We examined time kinetics of likely transcription factors and signaling molecules upstream of SOCS transcription, and survival of intracellular Mtb following SOCS upregulation. Our results suggest a plausible mechanism that involves PGE2 secretion during infection to induce the PKA/CREB axis, culminating in nuclear translocation of C/EBPß to induce expression of SOCS1. Mtb-infected Mϕ secreted IL-10, suggesting a mechanism of induction of STAT3, which may subsequently induce SOCS3. We provide evidence of temporal variation in SOCS isoform exspression and decay. Small-interfering RNA-mediated knockdown of SOCS1 and SOCS3 restored the pro-inflammatory milieu and reduced Mtb viability. In mice infected with Mtb, SOCS isoforms persisted across Days 28-85 post infection. Our results suggest that differential temporal regulation of SOCS isoforms by Mtb drives the host immune response towards a phenotype that facilitates the pathogen's survival.

Inhaled Adjunct Therapy with Second-Line Drug Candidates for Dose Reduction in Chemotherapeutic Regimens for Multi-drug-Resistant Tuberculosis.

Chemotherapy of multi-drug-resistant tuberculosis (TB) requires prolonged administration of multiple drugs. We investigated whether pulmonary delivery of minute doses of drugs, along with reduced oral doses of the same agents, would affect preclinical efficacy. We prepared dry powder inhalation (DPI) formulations comprising sutezolid (SUT), the second-generation pretomanid analog TBA-354 (TBA), or a fluorinated derivative of TBA-354 (32,625) in a matrix of the biodegradable polymer poly(L-lactide). We established formulation characteristics, doses inhaled by healthy mice, and preclinical efficacy in a mouse model of TB. Oral doses of 100 mg/kg/day or DPI doses of 0.25-0.5 mg/kg/day of drugs SUT, TBA-354, or 32,625 administered over 28 days were sub-optimally effective in reducing lung and spleen burden of Mycobacterium tuberculosis (Mtb) in infected mice. The addition of 0.25-0.5 mg/kg/day of SUT, TBA-354, or 32,625 as DPI to oral doses of 50 mg/kg/day was non-inferior in clearing Mtb from the lungs of infected mice. We concluded that adjunct therapy with inhaled second-line agents has the potential to reduce the efficacious oral dose.

Management of Hepatitis C in Children - A New Paradigm.

INTRODUCTION: With the advent of direct-acting antivirals (DAAs), the past decade has seen a paradigm shift in the management of hepatitis C (HCV) infection in children. In this review, we summarize the various treatment options for pediatric HCV infection, highlighting the recent changes in the management. METHODS: A literature search was performed using the PubMed database with the relevant keywords. Filters included were human, ages 0-18 years, and the English language. RESULTS: Initial phase of HCV treatment using conventional or pegylated interferon and ribavirin combination regimens yielded poor outcomes in children, especially in genotypes 1 and 4, with an overall sustained virologic response of 58%. Also, treatment with interferon and ribavirin combination was associated with significant side effects in up to 52% of those treated. Presently, various combinations of direct-acting antivirals (DAAs) have been approved in children above three years of age with documented evidence of high efficacy (SVR12 of 92% to 100%) and excellent safety, and the current standard of care. CONCLUSION: With various DAA regimens now being approved for children above three years of age, the treatment of active HCV infection (HCV-RNA positive) in children has become simple. Besides the effectiveness of DAA therapy, public awareness about HCV transmission, better screening, and making the DAAs available at a subsidized price in the public sectors are necessary to eliminate HCV infection in India.

Preparation and Evaluation of Low-Dose Calcitriol Dry Powder Inhalation as Host-Directed Adjunct Therapy for Tuberculosis.

BACKGROUND: It is unclear whether Vitamin D is efficacious as a host-directed therapy (HDT) for patients of tuberculosis (TB). We investigated pulmonary delivery of the active metabolite of Vitamin D3, i.e., 1, 25-dihydroxy vitamin D3 (calcitriol) in a mouse model of infection with Mycobacterium tuberculosis (Mtb). METHODS: We optimized a spray drying process to prepare a dry powder inhalation (DPI) of calcitriol using a Quality by Design (QbD) approach. We then compared outcomes when Mtb-infected mice were treated with inhaled calcitriol at 5 ng/kg as a stand-alone intervention versus DPI as adjunct to standard oral anti-tuberculosis therapy (ATT). RESULTS: The DPI with or without concomitant ATT markedly improved the morphology of the lungs and mitigated histopathology in both the lungs and the spleens. The number of nodular lesions on the lung surface decreased from 43.7 ± 3.1 to 22.5 ± 3.9 with the DPI alone and to 9.8 ± 2.5 with DPI + ATT. However, no statistically significant induction of host antimicrobial peptide cathelicidin or reduction in bacterial burden was seen with the DPI alone. DPI + ATT did not significantly reduce the bacterial burden in the lungs compared to ATT alone. CONCLUSIONS: We concluded that HDT using the low dose calcitriol DPI contributed markedly to mitigation of pathology, but higher dose may be required to evoke significant induction of bactericidal host response and bactericidal activity in the lung.

Transient, inhaled gene therapy with gamma interferon mitigates pathology induced by host response in a mouse model of tuberculosis.

Transient transfection of the respiratory mucosa of mice infected with Mycobacterium tuberculosis (Mtb) with gamma interferon (IFN-γ) promises benefits in disease therapy. We investigated preclinical efficacy of a dry powder inhalation (DPI) as a stand-alone versus adjunct to oral anti-tuberculosis (TB) chemotherapy in mice. We observed that this host-directed therapy mitigates the gross organ pathology and histopathology of lung and spleen tissue of infected mice receiving the DPI, either alone or as adjunct therapy. However, no statistically significant reduction in Mtb colony forming units (CFU) occurred if mice were given only DPI; but not drugs. We compared one and three doses a week of the DPI over four weeks; with or without concomitant oral drugs. There was no significant difference in lung CFU after four or 12 doses of the DPI alone, but, surprisingly, four doses were qualitatively better than 12 doses in mitigating lung pathology. Nodular lesions on the lung surface and the area occupied by these was significantly reduced after four doses of the DPI, even without oral drugs. Transient transfection with IFN-γ did not induce pathological inflammation of the lungs and airways. We conclude that IFN-γ, as expected of host-directed therapy, 'heals the host; ' but does not 'kill the bug.'

Transient Transfection of the Respiratory Epithelium with Gamma Interferon for Host-Directed Therapy in Pulmonary Tuberculosis.

Nebulized gamma interferon (IFN-γ) protein has been studied for clinical safety and efficacy against pulmonary tuberculosis (TB). The protein is expensive, requires a cold chain, and is difficult to deploy in limited-resource, high-incidence settings. We generated a preclinical proof of concept (PoC) for a dry powder inhalation (DPI) containing DNA constructs to transiently transfect the lung and airway epithelium of mice with murine IFN-γ. Bacterial colony-forming units (CFU) in the lungs of mice infected with Mycobacterium tuberculosis (Mtb) reduced from about 106/g of tissue to ~104 after four doses given once a week. Nodular inflammatory lesions in the lungs reduced significantly in number. Immunohistochemistry of infected lung sections for LC3-1 and LAMP-1 indicated autophagy induction between 18 and 48 h after inhalation. ELISA on bronchoalveolar lavage (BAL) fluid showed differences in kinetics of IFN-γ concentrations in the epithelial lining fluid of healthy versus infected mice. Uninfected mice receiving DNA constructs expressing a fluorescent protein were live-imaged. The fluorescence signals from the intracellular protein peaked at about 36 h after inhalation and declined by 48 h. These results establish preclinical PoC of the efficacy of a DPI and dosing regimen as a host-directed and transient gene therapy of experimental pulmonary TB in mice, justifying preclinical development.

Facile green synthesis of silicon nanoparticles from Equisetum arvense for fluorescence based detection of Fe(iii) ions.

Fluorescent silicon nanoparticles (SiNPs) might be one of the excellent candidates for use as optical markers in biological profiling and diagnostic applications. To exploit this perspective, they ought to be essentially synthesized from any green precursor rich in silicon. Stable dispersibility in water along with prolonged luminescence under different conditions is also desired. Moreover, one of the main challenges is to produce such optically (photoluminescence) stable and water-dispersible SiNPs. In our present work, we have reported the synthesis of a highly stable silicon nanoparticle aqueous suspension via a single-step microwave-assisted facile green route. Our as-prepared SiNPs exhibit inherent stable dispersibility, strong fluorescence, and photo-stable behavior. The experimental results demonstrate that the synthesized SiNPs are highly suitable for the detection of Fe(iii) ions. This optical sensing study opens a new avenue for use of SiNPs as a valuable optical probe in chemosensory applications. Our results provide a single-step methodology for the synthesis of highly stable SiNPs from a biological precursor, which can be used as a promising tool for various chemical and biological applications.

The structural and warm light emission properties of Sm3+/Tb3+ doubly doped strontium bismuth borosilicate glasses for LED applications.

Strontium Bismuth Borosilicate (SrBiBS as N) glasses doped with Tb3+ ions (N: Tb) and co-doped with Sm3+/Tb3+ (N: SmTb) were synthesized through the process of classical melt quenching. The structural and optical properties are investigated through energy dispersive spectroscopy; X-ray diffraction, Differential thermal analysis (DTA) and Fourier transform infrared spectra (FTIR), Optical absorption (OA) and photoluminescence (PL) spectral studies. X-ray diffraction indicates amorphous nature of glass. DTA curves explained the thermal stability and stress parameters of glasses. FTIR spectrum indicates existing vibrations of borate and silicate units. The absorption spectra have shown nine absorption bands of Tb3+ ions in the visible and NIR regions, due to transitions from ground state 7F6. In visible region, absorption spectra of co-doped glasses exhibited two bands of Tb3+ and three bands of Sm3+ with hyper sensitive transitions at 375 nm (7F6 → 5G6) and 401 nm (6H5/2 → 6P3/2). Photo Luminescence (PL) spectra of N: Tb and N: SmTb glasses is recorded at 375 nm excitation. N: Tb glasses have shown green emission corresponding to 5D4 → 7F5 transition. In all N: SmTb glasses, addition of Tb3+ ions has enhanced Sm3+ emission which is connected to quenching of Tb3+ emission. Moreover, 0.8 mol% of Tb3+ ions in co-doped glass (N: SmTb8) has shown maximum emission. The energy transfer process was inferred from shortening of decay times observed in N: SmTb glasses. The decay profiles fitted with Inokuti-Hirayama model suggests that the electric dipole-dipole interaction(S = 6) between Sm3+ and Tb3+ might dominate in energy transfer mechanism with probability PET and energy transfer parameter Q of 113-173 S-1 and 9.9-12.0 respectively. The color chromaticity (CIE) coordinates from PL emission of N: Tb & N: SmTb glasses have covered Green, Orange red and yellow (warm-light) regions with coordinates in ranges of x = 0.39-0.62 and y = 0.34-0.56.The color temperatures in range of 1713 K-4258 K.

Dehydroascorbate-derivatized chitosan particles for targeting antimalarial agents to infected erythrocytes.

The mammalian glucose transporter GLUT-1 and Plasmodium falciparum hexose transporter PfHT1 are overexpressed on human RBC infected with the parasite (iRBC), presumably for enhanced glucose uptake. Dehydroascorbic acid (DHA) competes out glucose in GLUT-1 binding. We prepared particles containing chloroquine phosphate using novel derivatives of chitosan (CSN). CSN was either pre-derivatized with DHA (PRE) or particles made of CSN were derivatized by surface-grafting DHA (POST). The optimized formulations were analyzed for size (170-200nm) drug content (about 40%) entrapment efficiency (50-57%), in vitro drug release (80% in 72h, Higuchi's model), hemolysis on exposure to whole blood or RBC at 5% hematocrit, cytotoxicity towards cultured HEK 293T (kidney) and HepG2 (hepatic) cells, targeting iRBC and in vitro efficacy against P. falciparum. PRE particles were superior to POST CSN particles in terms of uptake and extent of preferential targeting to iRBCs than RBCs. Unlike starch particles reported earlier, dextrose did not competitively inhibit uptake of DHA-derivatized CSN particles. Both formulations significantly induced parasite inhibition at 1nM while free drug showed comparable activity at 100nM. Both PRE and POST particles were superior to free drug in efficacy. Targeting with high efficiency promises dose reduction and possibility of overcoming efflux-based drug resistance.

Fluoride enrichment in an alluvial aquifer with its subsequent effect on human health in Birbhum district, West Bengal, India.

This research work primarily deals with the geochemistry and genesis of fluoride (F-) in an alluvial aquifer with an emphasis on prevalence of dental and skeletal fluorosis among the endemic population. Hydrogeochemical outcomes reveal that chemical weathering and ion-exchange phenomena are the two dominant processes that make study area groundwater into NaHCO3 water type. Presence of intercalated zeolite rich sediments (FTotal 412-446 mg/kg) having higher ion-exchange capacity (120-125 meq/100 g) within the aquifer is the source and mobilizing factors of F- in groundwater respectively. Laboratory experiment further justifies higher desorption potential of aquifer sediments at the groundwater pH of 6.5-7.5. Health survey reveals that out of 235 studied population 60% suffer from dental fluorosis while females >30 years of age became exposed early to osteoporosis disease.

Parameter optimization analysis to minimize the polarization error in a localized thermal tunable fiber ring resonator gyro.

The accuracy of the resonant frequency servo loop is a major concern for the high-performance operation of a resonant fiber optic gyro. For instance, a bias error as large as tens or even hundreds of degrees/hour has been observed at the demodulated output of the resonant frequency servo loop. The traditional frequency servo mechanism is not an efficient tool to address this problem. In our previous work, we proposed a novel method to minimize the laser frequency noise to the level of the shot noise by refractive index modulation by a thermally tunable resonator. In this paper, we performed the parameter optimization for the resonator coil, multifunction integrated-optics chip, and couplers by the transition matrix using the Jones matrix methodology to minimize the polarization error. With the optimized parameter values, we achieved the bias value of the resonator fiber optic gyro to 1.924°/h.

Efficient block processing of long duration biotelemetric brain data for health care monitoring.

In real time clinical environment, the brain signals which doctor need to analyze are usually very long. Such a scenario can be made simple by partitioning the input signal into several blocks and applying signal conditioning. This paper presents various block based adaptive filter structures for obtaining high resolution electroencephalogram (EEG) signals, which estimate the deterministic components of the EEG signal by removing noise. To process these long duration signals, we propose Time domain Block Least Mean Square (TDBLMS) algorithm for brain signal enhancement. In order to improve filtering capability, we introduce normalization in the weight update recursion of TDBLMS, which results TD-B-normalized-least mean square (LMS). To increase accuracy and resolution in the proposed noise cancelers, we implement the time domain cancelers in frequency domain which results frequency domain TDBLMS and FD-B-Normalized-LMS. Finally, we have applied these algorithms on real EEG signals obtained from human using Emotive Epoc EEG recorder and compared their performance with the conventional LMS algorithm. The results show that the performance of the block based algorithms is superior to the LMS counter-parts in terms of signal to noise ratio, convergence rate, excess mean square error, misadjustment, and coherence.

Efficient sorting of quantum-optical wave packets by temporal-mode interferometry.

Long-distance quantum communication relies on storing and retrieving photonic qubits in orthogonal field modes. The available degrees of freedom for photons are polarization, spatial-mode profile, and temporal/spectral profile. To date, methods exist for decomposing, manipulating, and analyzing photons into orthogonal polarization modes and spatial modes. Here we propose and theoretically verify the first highly efficient method to carry out analogous operations for temporally and spectrally overlapping, but field-orthogonal, temporal modes. The method relies on cascaded nonlinear-optical quantum frequency conversion.