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Efficient Adsorption and Desorption of Uranium(VI) Using a Polymeric Adsorbent: A Combined Theoretical and Experimental Approach with Real-Life Alkaline Leach Liquor
No full textAlkaline leaching is used for the extraction of uranium from rarely available carbonate ore. A hyperbranched cross-linked polymeric adsorbent (HCPA) was developed for selective recovery of uranium(VI) (U) from real-life alkaline leach liquor. HCPA was synthesized using the free radical copolymerization of acrylamide and N, N-methylene bis(acrylamide). In addition, potassium persulfate (as the initiator) and dodecanethiol (as the brancher) were used to transfer the radicals for faster chain formation and smooth branching of the long-chain polymer. Several methods were used extensively to characterize the adsorbent. The Langmuir maximum U adsorption capacity of HCPA was 1012 mg/g at 303 K, and 98% of U was removed from alkaline leach liquor. U was adsorbed at pH 8.5 in the presence of various interfering co-ions and desorbed at pH 11.5 in the form of sodium diuranate (Na2U2O7) precipitate. The adsorption was monolayer, exothermic, and spontaneous in nature. The C–N, CO–NH2, and C–OH groups of HCPA interacted with uranyl ions initiating the coordinative and electrostatic interactions leading to U adsorption. Continuous fixed-bed column runs were performed using the actual leach liquor, and a fundamental kinetic model was used to quantify the performance of columns. The transport parameters were estimated from the model, and scaling-up calculations were performed using these parameters. Five adsorption–desorption cycles were conducted to determine the reusability and structural stability of the synthesized polymeric adsorbent
Gravitational physics in the context of Indian astronomy: A vision document
No full textContributions from the Indian gravity community have played a significant role in shaping several branches of astronomy and astrophysics. This document reviews some of the most important contributions and presents a vision for gravity research in the context of astronomy and astrophysics in India. This is an expanded version of one of the chapters in the recently released Vision Document of the Astronomical Society of India
Strong-lensing cosmography using third-generation gravitational-wave detectors
No full textWe present a detailed exposition of a statistical method for estimating cosmological parameters from the observation of a large number of strongly lensed binary-black-hole (BBH) mergers observable by next (third) generation (XG) gravitational-wave (GW) detectors. This method, first presented in Jana, compares the observed number of strongly lensed GW events and their time delay distribution (between lensed images) with observed events to infer cosmological parameters. We show that the precision of the estimation of the cosmological parameters does not have a strong dependance on the assumed BBH redshift distribution model. Using the large number of unlensed mergers, XG detectors are expected to measure the BBH redshift distribution with sufficient precision for the cosmological inference. However, a biased inference of the BBH redshift distribution will bias the estimation of cosmological parameters. An incorrect model for the distribution of lens properties can also lead to a biased cosmological inference. However, Bayesian model selection can assist in selecting the right model from a set of available parametric models for the lens distribution. We also present a way to incorporate the effect of contamination in the data due to the limited efficiency of lensing identification methods, so that it will not bias the cosmological inference
A combination of systemic mannitol administration and mannitol-modified polyester nanoparticles facilitate gene delivery to the brain through caveolae-mediated endocytosis
No full textOvercoming the blood-brain barrier (BBB) remains a significant challenge for nucleic acid delivery to the brain. We have explored a combination of mannitol-modified poly (β-amino ester) (PBAE) nanoparticles and systemic mannitol injection for crossing the BBB. We incorporated mannitol in the PBAE polymer for caveolae targeting and also selected monomers that may help avoid delivery to the liver. We also induced caveolae at the BBB through systemic mannitol injection in order to create an opportunity for the caveolae-targeting nanoparticles (M30 D90)containing plasmid DNA to cross the BBB. When a clinically relevant dose was administered intravenously in this caveolae induction model, M30 D90 demonstrated significant transgene expression of a reporter plasmid in the brain, with selective uptake by neuronal cells and minimal liver accumulation. We also demonstrate that both caveolae modulation using systemic mannitol administration and caveolae targeting using designed nanoparticles are necessary for efficient delivery to the brain. This delivery platform offers a simple, scalable, and controlled delivery solution and holds promise for treating central nervous system diseases with functional targets
Non-viral delivery of nucleic acid for treatment of rare diseases of the muscle
No full textRare muscular disorders (RMDs) are disorders that affect a small percentage of the population. The disorders which are attributed to genetic mutations often manifest in the form of progressive weakness and atrophy of skeletal and heart muscles. RMDs includes disorders such as Duchenne muscular dystrophy (DMD), GNE myopathy, spinal muscular atrophy (SMA), limb girdle muscular dystrophy, and so on. Due to the infrequent occurrence of these disorders, development of therapeutic approaches elicits less attention compared with other more prevalent diseases. However, in recent times, improved understanding of pathogenesis has led to greater advances in developing therapeutic options to treat such diseases. Exon skipping, gene augmentation, and gene editing have taken the spotlight in drug development for rare neuromuscular disorders. The recent innovation in targeting and repairing mutations with the advent of CRISPR technology has in fact opened new possibilities in the development of gene therapy approaches for these disorders. Although these treatments show satisfactory therapeutic effects, the susceptibility to degradation, instability, and toxicity limits their application. So, an appropriate delivery vector is required for the delivery of these cargoes. Viral vectors are considered potential delivery systems for gene therapy; however, the associated concurrent immunogenic response and other limitations have paved the way for the applications of other non-viral systems like lipids, polymers, cell-penetrating peptides (CPPs), and other organic and inorganic materials. This review will focus on non-viral vectors for the delivery of therapeutic cargoes in order to treat muscular dystrophies
Affinity Propagation in Semi-Supervised Segmentation: A Biomedical Application
No full textGiven the scarcity of sufficient annotated data, using small sets of labeled samples under semi-supervision in biomedical imaging becomes necessary. Despite being highly successful, deep learning algorithms demand plenty of data to obtain significant performance. Complex data models make the usage of these methods costly. Selecting the correct model and tuning the hyperparameters of a model are also difficult jobs. Hence, a novel approach namely affinity propagation-based semi-supervised segmentation (APSS) is proposed. Here, affinity propagation clustering is modified and integrated with the advanced learning techniques that can efficiently use limited training data by discarding the completely exploited labeled data points. Moreover, a novel affinity calculation method is proposed considering both the Euclidean and geodesic distances to compute the distance between the two points on the histogram. This twofold contribution is tested using the three standard datasets (the International Skin Imaging Collaboration (ISIC) dermoscopic image dataset, the retinal fundus image dataset, and the liver tumor segmentation (LiTS) dataset). Results are compared with the three standard semi-supervised algorithms and four supervised algorithms. The effectiveness of the APSS approach in finding and exploiting the relationship between the labeled and unlabeled datasets is demonstrated in terms of qualitative (subjective evaluation and visual inspection) and quantitative performance (objective evaluation and numerical measurements)
Channel conformational plasticity of mitochondrial VDAC2 controls its interaction kinetics with cytosolic proteins
No full textIn mammals, VDAC exists in three isoforms, VDAC1, VDAC2, and VDAC3, each characterized by distinct tissue-dependent distribution and physiological role. VDAC2 is the most notable among the three isoforms because its knockout results in embryonic lethality and it regulates the BAK/BAX-dependent apoptosis pathways. Yet, the biophysical underpinnings of VDAC2 functions remain limited. In this study we reevaluate VDAC2’s properties, utilizing recombinant human VDAC2 WT and its three mutants, to understand the biophysical and structural basis that distinguishes VDAC2 from the other isoforms using single-molecule electrophysiology and solution NMR. We found that contrary to VDAC1 and VDAC3, which are characterized by a unique open state, VDAC2 displays dynamic switching between multiple high-conductive anion-selective open states. We employed α-synuclein—a known potent cytosolic regulator of VDAC1 and VDAC3—as a sensitive molecular probe, demonstrating that it induces characteristic blockage events in all open substates of VDAC2 but with up to 10 times different on-rates and blockage times. Despite profound changes in interaction kinetics, the substates exhibit the same equilibrium constant, which takes into account the blockage time, thus resulting in the same affinity of the α-synuclein-VDAC2 interaction. This striking observation suggests that once the α-synuclein molecule is captured, its physical state and interactions within the pore are conserved for all substates. These results imply that the α-synuclein molecule senses a structural change in the channel prior to its final capture within the pore. We propose that this conformational flexibility may allow VDAC2 to recognize a larger number of binding partners. This data could tentatively explain the physiological significance of VDAC2: its ability to dynamically adapt to metabolic cell conditions and to change the rates of interaction with its multiple protein partners
Plant histone variants at the nexus of chromatin readouts, stress and development
No full textHistones are crucial proteins that are involved in packaging the DNA as condensed chromatin inside the eukaryotic cell nucleus. Rather than being static packaging units, these molecules undergo drastic variations spatially and temporally to facilitate accessibility of DNA to replication, transcription as well as wide range of gene regulatory machineries. In addition, incorporation of paralogous variants of canonical histones in the chromatin is ascribed to specific functions. Given the peculiar requirement of plants to rapidly modulate gene expression levels on account of their sessile nature, histones and their variants serve as additional layers of gene regulation. This review summarizes the mechanisms and implications of distribution, modifications and differential incorporation of histones and their variants across plant genomes, and outlines emerging themes
Interplay of light and abscisic acid signaling to modulate plant development
No full textExogenous light cues and the phytohormone abscisic acid (ABA) regulate several aspects of plant growth and development. In recent years, the role of crosstalk between the light and ABA signaling pathways in regulating different physiological processes has become increasingly evident. This includes regulation of germination and early seedling development, control of stomatal development and conductance, growth, and development of roots, buds, and branches, and regulation of flowering. Light and ABA signaling cascades have various convergence points at both DNA and protein levels. The molecular crosstalk involves several light signaling factors such as HY5, COP1, PIFs, and BBXs that integrate with ABA signaling components such as the PYL receptors and ABI5. In particular, ABI5 and PIF4 promoters are key ‘hotspots’ for integrating these two pathways. Plants acquired both light and ABA signaling pathways before they colonized land almost 500 million years ago. In this review, we discuss recent advances in the interplay of light and ABA signaling regulating plant development and provide an overview of the evolution of these two pathways
