Ideal distortion-less bending of a focused non-paraxial electron beam

a b s t r a c t In specific applications, where electron beam is required to be bent after passing through the focusing optics, the beam spot on the target is distorted due to asymmetry introduced by the bending. For complete elimination of the above distortion, a circularly asymmetric initial velocity distribution of electrons that move in a radially decreasing magnetic field (i.e. index of field gradient ¼ 1) is proposed. The expression is quantitatively exact for beams with any angle of bending even when paraxial condition is not satisfied i.e. beam cross-sectional diameter is comparable with the radius of curvature of bending. Modified expression for the case, when kinetic energy of the electrons increases due to timevarying field during its motion through the bending magnetic field is also given as a result of which complexity of the magnetic field design (for strong focusing) can be avoided. Finally, a numerical model of electron gun is utilized to compare the results of proposed model

Oxidative stress, hormones, and effects of natural antioxidants on intestinal inflammation in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic, relapsing gastrointestinal (GI) disorder characterized by intestinal inflammation. The etiology of IBD is multifactorial and results from a complex interplay between mucosal immunity, environmental factors, and host genetics. Future therapeutics for GI disorders, including IBD, that are driven by oxidative stress require a greater understanding of the cellular and molecular mechanisms mediated by reactive oxygen species (ROS). In the GI tract, oxidative stressors include infections and pro-inflammatory responses, which boost ROS generation by promoting the production of pro-inflammatory cytokines. Nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2–related factor 2 (Nrf2) represent two important signaling pathways in intestinal immune cells that regulate numerous physiological processes, including anti-inflammatory and antioxidant activities. Natural antioxidant compounds exhibit ROS scavenging and increase antioxidant defense capacity to inhibit pro-oxidative enzymes, which may be useful in IBD treatment. In this review, we discuss various polyphenolic substances (such as resveratrol, curcumin, quercetin, green tea flavonoids, caffeic acid phenethyl ester, luteolin, xanthohumol, genistein, alpinetin, proanthocyanidins, anthocyanins, silymarin), phenolic compounds including thymol, alkaloids such as berberine, storage polysaccharides such as tamarind xyloglucan, and other phytochemicals represented by isothiocyanate sulforaphane and food/spices (such as ginger, flaxseed oil), as well as antioxidant hormones like melatonin that target cellular signaling pathways to reduce intestinal inflammation occurring with IBD

Allosteric “beta-blocker” isolated from a DNA-encoded small molecule library

The present study reports the discovery of a small-molecule negative allosteric modulator for the β2-adrenergic receptor (β2AR) via in vitro affinity-based iterative selection of highly diverse DNA-encoded small-molecule libraries. Characterization of the compound demonstrates its selectivity for the β2AR and that it negatively modulates a wide range of receptor functions. More importantly, our findings establish a generally applicable, proof-of-concept strategy for screening DNA-encoded small-molecule libraries against purified G-protein–coupled receptors (GPCRs), which holds great potential for discovering therapeutic molecules

Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G-protein-coupled receptor activation

G-protein coupled receptors (GPCRs) modulate many physiological processes by transducing a variety of extracellular cues into intracellular responses. Ligand binding to an extracellular orthosteric pocket propagates conformational change to the receptor cytosolic region to promote binding and activation of downstream signaling effectors such as G proteins and β-arrestins. It is widely appreciated that different agonists can share the same binding pocket but evoke unique receptor conformations leading to a wide range of downstream responses (i.e., ‘efficacy’)1. Furthermore, mounting biophysical evidence, primarily using the β-adrenergic receptor (β2AR) as a model system, supports the existence of multiple active and inactive conformational states2–5. However, how agonists with varying efficacy modulate these receptor states to initiate cellular responses is not well understood. Here we report stabilization of two distinct β2AR conformations using single domain camelid antibodies (nanobodies): a previously described positive allosteric nanobody (Nb80) and a newly identified negative allosteric nanobody (Nb60)6,7. We show that Nb60 stabilizes a previously unappreciated low affinity receptor state which corresponds to one of two inactive receptor conformations as delineated by X-ray crystallography and NMR spectroscopy. We find that the agonist isoproterenol has a 15,000-fold higher affinity for the β2AR in the presence of Nb80 compared to Nb60, highlighting the full allosteric range of a GPCR. Assessing the binding of 17 ligands of varying efficacy to the β2AR in the absence and presence of Nb60 or Nb80 reveals large ligand-specific effects that can only be explained using an allosteric model which assumes equilibrium amongst at least three receptor states. Agonists generally exert efficacy by stabilizing the active Nb80-stabilized receptor state (R80). In contrast, for a number of partial agonists, both stabilization of R80 and destabilization of the inactive, Nb60-bound state (R60) contribute to their ability to modulate receptor activation. These data demonstrate that ligands can initiate a wide range of cellular responses by differentially stabilizing multiple receptor states

Allosteric Nanobodies Reveal the Dynamic Range and Diverse Mechanisms of GPCR Activation

G-protein coupled receptors (GPCRs) modulate many physiological processes by transducing a variety of extracellular cues into intracellular responses. Ligand binding to an extracellular orthosteric pocket propagates conformational change to the receptor cytosolic region to promote binding and activation of downstream signaling effectors such as G proteins and β-arrestins. It is widely appreciated that different agonists can share the same binding pocket but evoke unique receptor conformations leading to a wide range of downstream responses (i.e., ‘efficacy’)1. Furthermore, mounting biophysical evidence, primarily using the β-adrenergic receptor (β2AR) as a model system, supports the existence of multiple active and inactive conformational states2–5. However, how agonists with varying efficacy modulate these receptor states to initiate cellular responses is not well understood. Here we report stabilization of two distinct β2AR conformations using single domain camelid antibodies (nanobodies): a previously described positive allosteric nanobody (Nb80) and a newly identified negative allosteric nanobody (Nb60)6,7. We show that Nb60 stabilizes a previously unappreciated low affinity receptor state which corresponds to one of two inactive receptor conformations as delineated by X-ray crystallography and NMR spectroscopy. We find that the agonist isoproterenol has a 15,000-fold higher affinity for the β2AR in the presence of Nb80 compared to Nb60, highlighting the full allosteric range of a GPCR. Assessing the binding of 17 ligands of varying efficacy to the β2AR in the absence and presence of Nb60 or Nb80 reveals large ligand-specific effects that can only be explained using an allosteric model which assumes equilibrium amongst at least three receptor states. Agonists generally exert efficacy by stabilizing the active Nb80-stabilized receptor state (R80). In contrast, for a number of partial agonists, both stabilization of R80 and destabilization of the inactive, Nb60-bound state (R60) contribute to their ability to modulate receptor activation. These data demonstrate that ligands can initiate a wide range of cellular responses by differentially stabilizing multiple receptor states

Decolonizing ethnography and Tribes in India

This article unravels the many ways of doing ethnography within the area of Tribal studies in India. Historically (methodologically), studies concerning Tribes in India were dominated by colonial ethnographers and explorers. Subsequently, in post-colonial India, such studies became the field of a dominant male caste. From a similar perspective of dominance, these studies on Tribes in India viewed them as either backward or from the point of view that "civilization" could be achieved only through bringing them into the mainstream. Scholars who followed such frames of reference failed to reflect on their own dominant social positions in engaging in research projects with their Tribal subjects. Moreover, some of them even stated to have been inspired by the studies of Malinowski, whose methodology is considered to be uncritical, non-sensitive, and non-reflexive, especially while relating to Tribal studies. The Tribal people in India, therefore, continued to be framed within such a dominant caste perspective, without the slightest effort to treat them as non-caste societies or as equals within caste societies. Methodologically, by positioning myself against such frames of reference while engaging in research within the context of Tribes in India, I draw my research frameworks from those of indigenous methodologies to explore the possibilities of decolonizing ethnography by recognizing many ways of doing. Empirically, I base my engagement with a specific Tribal group (Tripura Tribe) in Tripura, Northeast India. As an indigenous community within the Indian state of Tripura, Tripura people's epistemology/worldviews differ from that of the majoritarian $\it Savarna$ caste society. With an intent to decolonize ethnography from an indigenous context, in this article, I demonstrate the many ways of doing ethnography by innovatively engaging with three related methods, namely, the conversational method, engaged observation, and sitting around the fire. This article argues that for any researcher, when engaging in research within the context of Tribes, the methods and frame of reference employed must be congruent with indigenous ways of being, knowing, and doing. Furthermore, it also insists that critical reflexivity, responsibility, and sensitivity are keys to Tribal studies in India

Ear Recognition Using Rank Level Fusion of Classifiers Outputs

An individual's authentication plays a vital role in our daily life. In the last decade, biometric-based authentication has become more prevalent than traditional approaches like passwords and pins.   Ear recognition has gained attention in the biometric community in recent years. Researchers defined several features for the identification of a person from ear image. The features play a vital role in the success of classification models. This paper considers an ensemble of features for designing a new classification model. The features are assessed in isolation as well as through feature-level fusion.  Subsequently, a rank-level fusion for classification is introduced. The experiments are conducted on both constrained and unconstrained ear datasets. The results are promising and open up new possibilities in machine learning-based ear recognitio

Intelligent Road Management System for Autonomous, Non-Autonomous, and VIP Vehicles

Currently, autonomous vehicles, non-autonomous vehicles, and VIP (emergency) autonomous cars are using intelligent road management techniques to interact with one another and enhance the effectiveness of the traffic system. All sorts of vehicles are managed and under control using the intersection management unit approach. This study focuses on transportation networks where VIP cars are a major disruption, accounting for 40% of accidents and 80% of delays. Intelligent Mobility (IM) is a strategy promoted in this study that proposes setting up intelligent channels for all vehicle communication. As part of its function, the IM unit keeps tabs on how often each junction is used so that it may notify drivers on traffic conditions and ease their workload. The suggested layout may drastically cut average wait times at crossings, as shown in SUMO simulations. The entrance of a VIP car should disrupt all traffic, but the IM (intersection management) unit effectively manages all traffic by employing preemptive scheduling and non-preemptive scheduling techniques for all types of vehicles. We are employing Nishtar roads, the M4 motorway, Mexico, and Washington roads in our scenario. In comparison to all other routes, the simulation results demonstrate that the Washington road route is better able to manage all vehicle kinds. Washington’s traffic delays for 50 cars of all sorts are 4.02 s for autonomous vehicles, 3.62 s for VIP autonomous vehicles, and 4.33 s for non-autonomous vehicles

Eudragit S100 Coated Citrus Pectin Nanoparticles for Colon Targeting of 5-Fluorouracil

In the present study, Eudragit S100 coated Citrus Pectin Nanoparticles (E-CPNs) were prepared for the colon targeting of 5-Fluorouracil (5-FU). Citrus pectin also acts as a ligand for galectin-3 receptors that are over expressed on colorectal cancer cells. Nanoparticles (CPNs and E-CPNs) were characterized for various physical parameters such as particle size, size distribution, and shape etc. In vitro drug release studies revealed selective drug release in the colonic region in the case of E-CPNs of more than 70% after 24 h. In vitro cytoxicity assay (Sulphorhodamine B assay) was performed against HT-29 cancer cells and exhibited 1.5 fold greater cytotoxicity potential of nanoparticles compared to 5-FU solution. In vivo data clearly depicted that Eudragit S100 successfully guarded nanoparticles to reach the colonic region wherein nanoparticles were taken up and showed drug release for an extended period of time. Therefore, a multifaceted strategy is introduced here in terms of receptor mediated uptake and pH-dependent release using E-CPNs for effective chemotherapy of colorectal cancer with uncompromised safety and efficacy