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The treatment of opioid withdrawal is an important area of clinical concern when treating patients with chronic, non-cancer pain, patients with active opioid use disorder, and patients receiving medication for opioid use disorder. Current standards of care for medically supervised withdrawal include treatment with μ-opioid receptor agonists, (eg, methadone), partial agonists (eg, buprenorphine), and α2-adrenergic receptor agonists (eg, clonidine and lofexidine). Newer agents likewise exploit these pharmacological mechanisms, including tramadol (μ-opioid receptor agonism) and tizanidine (α2 agonism). Areas for future research include managing withdrawal in the context of stabilising patients with opioid use disorder to extended-release naltrexone, transitioning patients with opioid use disorder from methadone to buprenorphine, and tapering opioids in patients with chronic, non-cancer pain.

Over India, heat waves occur during the summer months of April to June. A gridded daily temperature data set for the period, 1961–2013 has been analyzed to examine the variability and trends in heat waves over India. For identifying heat waves, the Excess Heat Factor (EHF) and 90 th percentile of maximum temperatures were used. Over central and northwestern parts of the country, frequency, total duration and maximum duration of heat waves are increasing. Anomalous persistent high with anti-cyclonic flow, supplemented with clear skies and depleted soil moisture are primarily responsible for the occurrence of heat waves over India. Variability of heat waves over India is influenced by both the tropical Indian Ocean and central Pacific SST anomalies. The warming of the tropical Indian Ocean and more frequent El Nino events in future may further lead to more frequent and longer lasting heat waves over India.

Root-hair growth and development regulated by soil microbes is associated with auxin. In this background, we hypothesized that mycorrhizal fungal inoculation induces greater root-hair growth through stimulated auxin synthesis and transport under water stress conditions. Trifoliate orange ( Poncirus trifoliata ) was inoculated with an arbuscular mycorrhizal (AM) fungus ( Funneliformis mosseae ) under well-watered (WW) and drought stress (DS) for 9 weeks. Compared with non-AM seedlings, AM seedlings displayed significantly higher density, length, and diameter of root hairs and root indoleacetic acid (IAA) level, whereas lower total root IAA efflux, regardless of soil moisture status. Root PtYUC3 and PtYUC8 involved in IAA biosynthesis were up-regulated by mycorrhization under WW and DS, whereas AM-modulated expression in PtTAA1 , PtTAR2 , PtYUC4 , and PtYUC6 depended on status of soil moisture. Mycorrhizal inoculation down-regulated the transcript level of root auxin efflux carriers like PtPIN1 and PtPIN3 , whereas significantly up-regulated the expression of root auxin-species influx carriers like PtABCB19 and PtLAX2 under DS. These results indicated that AMF-stimulated greater root-hair growth of trifoliate orange under DS that is independent on AMF species is related with mycorrhiza-modulated auxin synthesis and transport, which benefits the host plant to enhance drought tolerance.

Food security will be increasingly challenged by climate change, natural resource degradation, and population growth. Wheat yields, in particular, have already stagnated in many regions and will be further affected by warming temperatures. Despite these challenges, wheat yields can be increased by improving management practices in regions with existing yield gaps. To identify the magnitude and causes of current yield gaps in India, one of the largest wheat producers globally, we produced 30 meter resolution yield maps from 2001 to 2015 across the Indo-Gangetic Plains (IGP), the nation's main wheat belt. Yield maps were derived using a new method that translates satellite vegetation indices to yield estimates using crop model simulations, bypassing the need for ground calibration data. This is one of the first attempts to apply this method to a smallholder agriculture system, where ground calibration data are rarely available. We find that yields can be increased by 11% on average and up to 32% in the eastern IGP by improving management to current best practices within a given district. Additionally, if current best practices from the highest-yielding state of Punjab are implemented in the eastern IGP, yields could increase by almost 110%. Considering the factors that most influence yields, later sow dates and warmer temperatures are most associated with low yields across the IGP. This suggests that strategies to reduce the negative effects of heat stress, like earlier sowing and planting heat-tolerant wheat varieties, are critical to increasing wheat yields in this globally-important agricultural region.

This study presents an approach for security-constrained unit commitment (SCUC) with integration of an energy storage system (ESS) and wind generation. Compressed air energy storage (CAES) is considered as an alternative solution to store energy. For economical operation and control purposes, utilities with CAES are interested in the availability and the dispatch of CAES on an hourly basis, given the specific characteristics of CAES. The main contribution of this study is the development of enhanced SCUC formulation and solution techniques with wind power, CAES and multiple constraints including fuel and emission limit. Proposed approach allows simultaneous optimisation of the energy and the ancillary services. Case studies with eight-bus and 118-bus systems are presented to validate the proposed model. This study also contributes by conducting comprehensive studies to analyse the impact of CAES system on locational pricing, economics, peak-load shaving, transmission congestion management, wind curtailment and environmental perspective.

The iPSC-derived 3D models are considered to be a connective link between 2D culture and in vivo studies. However, the sensitivity of such 3D models is yet to be established. We assessed the sensitivity of the hiPSC-derived 3D spheroids against 2D cultures of neural progenitor cells. The sub-toxic dose of Sodium Arsenite (SA) was used to investigate the alterations in miRNA-proteins in both systems. Though SA exposure induced significant alterations in the proteins in both 2D and 3D systems, these proteins were uncommon except for 20 proteins. The number and magnitude of altered proteins were higher in the 2D system compared to 3D. The association of dysregulated miRNAs with the target proteins showed their involvement primarily in mitochondrial bioenergetics, oxidative and ER stress, transcription and translation mechanism, cytostructure, etc., in both culture systems. Further, the impact of dysregulated miRNAs and associated proteins on these functions and ultrastructural changes was compared in both culture systems. The ultrastructural studies revealed a similar pattern of mitochondrial damage, while the cellular bioenergetics studies confirm a significantly higher energy failure in the 2D system than to 3D. Such a higher magnitude of changes could be correlated with a higher amount of internalization of SA in 2D cultures than in 3D spheroids. Our findings demonstrate that a 2D culture system seems better responsive than a 3D spheroid system against SA exposure. Graphical Abstract

Non-enzymatic glycation is the addition of free carbonyl group of reducing sugar to the free amino groups of proteins, resulting in the formation of a Schiff base and an Amadori product. Dihydroxyacetone (DHA) is one of the carbonyl species which reacts rapidly with the free amino groups of proteins to form advanced glycation end products (AGEs). The highly reactive dihydroxyacetone phosphate is a derivative of dihydroxyacetone (DHA), and a product of glycolysis, having potential glycating effects to form AGEs. The formation of AGEs results in the generation of free radicals which play an important role in the pathophysiology of aging and diabetic complications. While the formation of DHA-AGEs has been demonstrated previously, no extensive studies have been performed to assess the inhibition of AGE inhibitors at all the three stages of glycation (early, intermediate and late) using metformin (MF) and pyridoxamine (PM) as a novel inhibitor. In this study we report glycation of human serum albumin (HSA) & its characterization by various spectroscopic techniques. Furthermore, inhibition of glycation products at all the stages of glycation was also studied. Spectroscopic analysis suggests structural perturbations in the HSA as a result of modification which might be due to generation of free radicals and formation of AGEs. The inhibition in the formation of glycation reaction reveals that Pyridoxamine is a better antiglycating agent than Metformin at all stages of the glycation (early, intermediate and late stages).

This paper systematically reviews the progress on the HgCdTe (MCT) material deposition via molecular-beam epitaxy (MBE) and previously reported atomistic approaches used to model the MCT epitaxy. The structure design and fabrication of the infrared (IR) detection systems require highly crystalline MCT films. The state-of-the-art of the MBE growth processes of Hg1−xCdxTe films over Si, GaAs, GaSb, and CdZnTe substrates are reported here from an atomistic simulation perspective. The most advanced in-house-developed kinetic Monte Carlo (kMC) technique, coupled with the geometry of the MBE reactor (implemented in the TNL-EpiGrowTM simulator) is exploited to reproduce real-time MBE experiments. The ability to track each atom involved in the adsorption, diffusion, and desorption processes over the lattice provides deeper insights. The ability to map various defects quantitatively and qualitatively during the growth process in a layer-by-layer and island mode helps to provide a proper understanding of their formation. The TNL-EpiGrowTM simulator provides an innovative and cost-effective solution for the epitaxial growth processes associated with MBE, CVD, and MOCVD reactors for most semiconductors. The types of defects, their position over the lattice, layer-by-layer strain, surface roughness, lattice parameters are easily extractable and provide an unmatched solution. However, it is very difficult to realize similar solutions through sophisticated instruments. Si, GaAs, GaSb, and CdZnTe substrates have been used to reproduce the MBE process of Hg1−xCdxTe (x ≈ 0.55). The vacancies and dislocation densities are reported here to characterize the cases of MCT epitaxy on the four different substrates. The growth rates of CdTe and MCT have been benchmarked against the experimental data (Pacuski et al. in Cryst Growth Des 17(6):2987, 2017; Wijewamauriya et al. in Appl Phys Lett 51(24):2025, 1987). The output results revealed that CdZnTe is the most attractive substrate choice but, due to its technological challenges, GaSb can replace it and is the most suitable option for the growth of Hg1−xCdxTe as compared to Si and GaAs substrates under similar conditions. The results reported here also support the experimental findings (Gu et al. in J Cryst Growth 468:216, 2017). The dislocations and vacancies generated in the GaSb substrate are comparable to those in the CdZnTe substrate.

The amygdala is central to the pathophysiology of many psychiatric illnesses. An imprecise understanding of how the amygdala fits into the larger network organization of the human brain, however, limits our ability to create models of dysfunction in individual patients to guide personalized treatment. Therefore, we investigated the position of the amygdala and its functional subdivisions within the network organization of the brain in 10 highly sampled individuals (5 h of fMRI data per person). We characterized three functional subdivisions within the amygdala of each individual. We discovered that one subdivision is preferentially correlated with the default mode network; a second is preferentially correlated with the dorsal attention and fronto-parietal networks; and third subdivision does not have any networks to which it is preferentially correlated relative to the other two subdivisions. All three subdivisions are positively correlated with ventral attention and somatomotor networks and negatively correlated with salience and cinguloopercular networks. These observations were replicated in an independent group dataset of 120 individuals. We also found substantial across-subject variation in the distribution and magnitude of amygdala functional connectivity with the cerebral cortex that related to individual differences in the stereotactic locations both of amygdala subdivisions and of cortical functional brain networks. Finally, using lag analyses, we found consistent temporal ordering of fMRI signals in the cortex relative to amygdala subdivisions. Altogether, this work provides a detailed framework of amygdala–cortical interactions that can be used as a foundation for models relating aberrations in amygdala connectivity to psychiatric symptoms in individual patients.

Kink oscillations of coronal loops, i.e., standing kink waves, is one of the most studied dynamic phenomena in the solar corona. The oscillations are excited by impulsive energy releases, such as low coronal eruptions. Typical periods of the oscillations are from a few to several minutes, and are found to increase linearly with the increase in the major radius of the oscillating loops. It clearly demonstrates that kink oscillations are natural modes of the loops, and can be described as standing fast magnetoacoustic waves with the wavelength determined by the length of the loop. Kink oscillations are observed in two different regimes. In the rapidly decaying regime, the apparent displacement amplitude reaches several minor radii of the loop. The damping time which is about several oscillation periods decreases with the increase in the oscillation amplitude, suggesting a nonlinear nature of the damping. In the decayless regime, the amplitudes are smaller than a minor radius, and the driver is still debated. The review summarises major findings obtained during the last decade, and covers both observational and theoretical results. Observational results include creation and analysis of comprehensive catalogues of the oscillation events, and detection of kink oscillations with imaging and spectral instruments in the EUV and microwave bands. Theoretical results include various approaches to modelling in terms of the magnetohydrodynamic wave theory. Properties of kink oscillations are found to depend on parameters of the oscillating loop, such as the magnetic twist, stratification, steady flows, temperature variations and so on, which make kink oscillations a natural probe of these parameters by the method of magnetohydrodynamic seismology.