Four Nepali Short Stories

Introduced and translated by Theodore Riccardi, Jr. Circumstantial Evidence by Pushkar Shamsher; The Ward by Sri Guruprasad Mainali; Nicotine Fit by Balkrishna Sama; The Surmawalla of Delhi by Sivakumar Rai

Immuno-silent polymer capsules encapsulating nanoparticles for bioimaging applications

PEGylated polymer capsules encapsulating LaVO4:Tb3+, GdVO4:Tb3+, Gd2O3:Tb3+, GdF3:Tb3+, YVO4:Tb3+ and iron oxide nanoparticles are promising new fluorescence, magnetic and magnetofluorescence imaging agents. Recently, we have reported the in vitro and in vivo level toxicity profile which shows the non-toxic nature of polymer capsules encapsulating nanoparticles. However, prior to clinical use, it is essential to ensure that these agents are unlikely to activate immune responses. Herein, we investigated the immuno-compatibility of polymer capsules with dendritic cells (DC) and macrophages (MO), major antigen presenting cell (APC) subsets required for activation of innate and adaptive immunity. Capsules were efficiently internalized by both DC and MO in vitro. Importantly, despite the presence of intracellular capsules, there was no significant impact on the viability of cells. We studied the impact of different capsules on the cytokine profile of DC and MO, known to be important for the polarization of T-cell immunity. None of the capsules elicited change in cytokine secretion from DC. Furthermore, capsules did not alter the polarization of either M1 or M2 MO subsets as determined by the balance of IL-12 and IL-10 secretion. These data support the notion that PEGylated polymer capsules loaded with nanoparticles have the potential to remain immunologically silent as they do not activate APC and neither do they hinder the response of DC or MO to pathogen activating signals. These systems, therefore, exhibit promising characteristics for bioimaging applications. KEYWORDS: PEGylated polymer capsules, M1 and M2 macrophages, dendritic cells, immune respons

Implementation of Transmission Line Fault Detection System using Long Range Wireless Sensor Networks

This paper proposes a fault detection system designed for transmission lines using Long-Range Wireless Sensor Network (LoRAWSN). The system is designed to detect and locate faults across transmission lines in real-time, which can significantly improve the reliability and efficiency of power transmission systems. A WSN will be built across transmission lines over an area. The faults identified by these sensor nodes is then transmitted to a central control unit, which analyses and displays the data. The LoRaWAN technology enables the WSN to cover long distances while consuming minimal power, making it ideal for monitoring transmission lines. The proposed fault detection system is evaluated through real world experiments, which demonstrate the feasibility and effectiveness of the proposed system. Overall, this paper presents a novel and practical approach for fault detection on transmission lines, which has the potential to improve the reliability and efficiency of power transmission systems

Generic Delivery of Payload of Nanoparticles Intracellularly via Hybrid Polymer Capsules for Bioimaging Applications

Towards the goal of development of a generic nanomaterial delivery system and delivery of the ‘as prepared’ nanoparticles without ‘further surface modification’ in a generic way, we have fabricated a hybrid polymer capsule as a delivery vehicle in which nanoparticles are loaded within their cavity. To this end, a generic approach to prepare nanomaterials-loaded polyelectrolyte multilayered (PEM) capsules has been reported, where polystyrene sulfonate (PSS)/polyallylamine hydrochloride (PAH) polymer capsules were employed as nano/microreactors to synthesize variety of nanomaterials (metal nanoparticles; lanthanide doped inorganic nanoparticles; gadolinium based nanoparticles, cadmium based nanoparticles; different shapes of nanoparticles; co-loading of two types of nanoparticles) in their hollow cavity. These nanoparticles-loaded capsules were employed to demonstrate generic delivery of payload of nanoparticles intracellularly (HeLa cells), without the need of individual nanoparticle surface modification. Validation of intracellular internalization of nanoparticles-loaded capsules by HeLa cells was ascertained by confocal laser scanning microscopy. The green emission from Tb3+ was observed after internalization of LaF3:Tb3+(5%) nanoparticles-loaded capsules by HeLa cells, which suggests that nanoparticles in hybrid capsules retain their functionality within the cells. In vitro cytotoxicity studies of these nanoparticles-loaded capsules showed less/no cytotoxicity in comparison to blank capsules or untreated cells, thus offering a way of evading direct contact of nanoparticles with cells because of the presence of biocompatible polymeric shell of capsules. The proposed hybrid delivery system can be potentially developed to avoid a series of biological barriers and deliver multiple cargoes (both simultaneous and individual delivery) without the need of individual cargo design/modification

On the controlled isotropic shrinkage induced fine-tuning of photo-luminescence in terbium ions embedded silica inverse opal films

Tb3+ embedded silica inverse opal structures with different photonic stop bands have been fabricated by annealing the SiO2-polystyrene spheres (diameter 390 nm) opal template at 320-650 oC. The PSB tuning realized in the wavelength range 498 – 600 nm is shown to depend on annealing temperature and impending isotropic shrinkage of silica matrix. The impact of wide PSB shift on four Tb3+ ion emission bands (blue, green, yellow, and red at 486, 545, 580, and 620 nm, respectively) corresponding to 5D4→7Fj (j = 6,5,4,3) transitions have been investigated. The effect amounts to significant suppression of emission bands at 586, 545 and 486 nm in inverse opals, obtained by annealing opal template at 350, 400, and 650 oC, respectively. Further, luminescence lifetime of Tb3+ ion 5D4 state increases with shrinkage induced in inverse opal progressively and get enhanced up to 2.3 times vis-à-vis reference silica. The changes in refractive index caused by thermal annealing of opal template is found to be responsible for the observed improvement in 5D4 state lifetime

Intracellular Delivery of β‑Galactosidase Enzyme Using Arginase-Responsive Dextran Sulfate/Poly‑l‑arginine Capsule for Lysosomal Storage Disorder

β-Galactosidase (β-gal) is one of the important lysosomal enzymes that is involved in the breakdown of glycosphingolipids (e.g., GM1 ganglioside), and its deficiency leads to GM1 Gangliosidosis, a lysosomal storage disorder (LSD). Intracellular delivery of β-gal is one of the preferable methods to treat this kind of LSDs. However, it cannot permeate the cell membrane due to its intricate macromolecular nature, low stability, and degradation by endogenous proteases. To this end, we report efficient intracellular delivery of β-gal via arginase-responsive dextran sulfate/poly-l-arginine polymer capsules (DS/PA capsules). The therapeutic activity of β-gal enzyme has been assessed in two gene-deficient diseased cell lines, SV (β-galactosidase gene-deficient mouse fibroblast) and R201C (deficient human β-galactosidase gene-introduced mouse fibroblast), and in wild-type mouse fibroblast immortalized cell lines. The activity of β-gal enzyme has been estimated within cells by using fluorescein isothiocyanate-cholera toxin B as a florescent probe that illustrates the level of GM1 ganglioside, the β-gal substrate. We found 1.8-, 3.4-, and 2.8-fold reduction in the substrate level in R201C, SV, and wild-type mouse fibroblast, respectively, which confirms the release and therapeutic activity of β-gal enzyme inside the cells. Moreover, enzyme delivery in gene-deficient diseased cell lines (SV and R201C) via DS/PA capsules reduced the level of enzyme substrate to a normal endogenous level, which is present in untreated wild-type mouse fibroblast cells. We note that loading of β-gal enzyme within DS/PA capsules was estimated to be 3 mU per hundred capsules and more than 77% of β-gal is released within 12 h. Overall, these results highlight the potential of DS/PA capsules as an efficient delivery carrier for therapeutic enzyme

Targeted Stealth Polymer Capsules Encapsulating Ln³⁺-Doped LaVO₄ Nanoparticles for Bioimaging Applications

We report synthesis of targeted PEGylated polymer capsules encapsulating Stoke’s shift and upconverting LaVO₄ nanoparticles by following a unique approach for bioimaging applications. First, LaVO₄:Ln³⁺@silica (Ln³⁺ = Tb³⁺, Eu³⁺, and Yb³⁺/Er³⁺) core–shell nanoparticles are prepared by sol–gel method followed by layer-by-layer assembly of polymers and PEGylation over core–shell particles. Second, removal of silica core facilitates the trapping of LaVO₄:Ln³⁺ nanoparticles inside the PEGylated polymer capsules. Finally, capsules are surface modified with antibodies to target cancer cells. The nanoparticles-loaded polymer capsules are found to be internalized and biocompatible with various cells (e.g., HeLa, A498, H460, MCF-7, Schwann, L929, and IC-21) suggesting their applicability in different types of cells. In addition, the capsules modified with antibodies show more specific uptake suggesting their targeting ability by 3-fold for MCF-7 and 10-fold for H460 cancer cells. Moreover, the nanoparticle-loaded polymer capsules were internalized by HeLa cells via macropinocytosis mechanism. We observed localized bright Stoke’s shift (Tb³⁺ ions, λ_ex = 488 nm) and upconversion (Er³⁺ ions, λ_ex = 980 nm) green fluorescence from cells suggesting their potential use as targeted bioimaging agents