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"Ahmed, H"
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4D visualization of matter : recent collected works
\"This anthology is an exposé of the Collected Works that have emerged over the past decade from Caltech. Through recent publications, the volume provides overviews of the principles, the electron-based techniques, and the applications made.\"-- Back cover.
Book
Four-Dimensional Electron Microscopy
The discovery of the electron over a century ago and the realization of its dual character have given birth to one of the two most powerful imaging instruments: the electron microscope. The electron microscope's ability to resolve three-dimensional (3D) structures on the atomic scale is continuing to affect different fields, including materials science and biology. In this Review, we highlight recent developments and inventions made by introducing the fourth dimension of time in electron microscopy. Today, ultrafast electron microscopy (4D UEM) enables a resolution that is 10 orders of magnitude better than that of conventional microscopes, which are limited by the video-camera rate of recording. After presenting the central concept involved, that of single-electron stroboscopie imaging, we discuss prototypical applications, which include the visualization of complex structures when unfolding on different length and time scales. The developed UEM variant techniques are several, and here we illucidate convergent-beam and near-field imaging, as well as tomography and scanning-pulse microscopy. We conclude with current explorations in imaging of nanomaterials and biostructures and an outlook on possible future directions in space-time, 4D electron microscopy.
Journal Article
Reflections on world affairs : peace and politics
\"This volume, the collected work, is an assemblage of the author's Reflections on World Affairs : Peace and Politics. The focus is on education, science for the have-nots--as well as for the haves--and science in diplomacy. Prof. Zewail believes that the use of the 'soft power' of education, diplomacy, and economic development is far more effective, and much less expensive, than the hegemony of military aggression or politicized foreign aid. From his unique position straddling between East-West cultures and values, it is clear that most problems in our world arise from 'not knowing' and 'not having.' It follows that education is critical, not only for enlightenment, or the 'knowing,' but also for boosting productivity and enhancing the 'having'\"--Provided by publisher.
Book
Habit, choice, and addiction
Addiction was suggested to emerge from the progressive dominance of habits over goal-directed behaviors. However, it is generally assumed that habits do not persist in choice settings. Therefore, it is unclear how drug habits may persist in real-world scenarios where this factor predominates. Here, we discuss the poor translational validity of the habit construct, which impedes our ability to determine its role in addiction. New evidence of habitual behavior in a drug choice setting are then described and discussed. Interestingly, habitual preference did not promote drug choice but instead favored abstinence. Here, we propose several clues to reconcile these unexpected results with the habit theory of addiction, and we highlight the need in experimental research to face the complexity of drug addicts’ decision-making environments by investigating drug habits in the context of choice and in the presence of cues. On a theoretical level, we need to consider more complex frameworks, taking into account continuous interactions between goal-directed and habitual systems, and alternative decision-making models more representative of real-world conditions.
Journal Article
A Comprehensive Overview of Globally Approved JAK Inhibitors
Janus kinase (JAK) is a family of cytoplasmic non-receptor tyrosine kinases that includes four members, namely JAK1, JAK2, JAK3, and TYK2. The JAKs transduce cytokine signaling through the JAK-STAT pathway, which regulates the transcription of several genes involved in inflammatory, immune, and cancer conditions. Targeting the JAK family kinases with small-molecule inhibitors has proved to be effective in the treatment of different types of diseases. In the current review, eleven of the JAK inhibitors that received approval for clinical use have been discussed. These drugs are abrocitinib, baricitinib, delgocitinib, fedratinib, filgotinib, oclacitinib, pacritinib, peficitinib, ruxolitinib, tofacitinib, and upadacitinib. The aim of the current review was to provide an integrated overview of the chemical and pharmacological data of the globally approved JAK inhibitors. The synthetic routes of the eleven drugs were described. In addition, their inhibitory activities against different kinases and their pharmacological uses have also been explained. Moreover, their crystal structures with different kinases were summarized, with a primary focus on their binding modes and interactions. The proposed metabolic pathways and metabolites of these drugs were also illustrated. To sum up, the data in the current review could help in the design of new JAK inhibitors with potential therapeutic benefits in inflammatory and autoimmune diseases.
Journal Article
The Multifaceted Role of L-Type Amino Acid Transporter 1 at the Blood–Brain Barrier: Structural Implications and Therapeutic Potential
L-type amino acid transporter 1 (LAT1) is integral to the transport of large neutral amino acids across the blood–brain barrier (BBB), playing a crucial role in brain homeostasis and the delivery of therapeutic agents. This review explores the multifaceted role of LAT1 in neurological disorders, including its structural and functional aspects at the BBB. Studies using advanced BBB models, such as induced pluripotent stem cell (iPSC)–derived systems and quantitative proteomic analyses, have demonstrated LAT1’s significant impact on drug permeability and transport efficiency. In Alzheimer’s disease, LAT1-mediated delivery of anti-inflammatory and neuroprotective agents shows promise in overcoming BBB limitations. In Parkinson’s disease, LAT1’s role in transporting L-DOPA and other therapeutic agents highlights its potential in enhancing treatment efficacy. In phenylketonuria, studies have revealed polymorphisms and genetic variations of LAT1, which could be correlated to disease severity. Prodrugs of valproic acid, pregabalin, and gabapentin help use LAT1-mediated transport to increase the therapeutic activity and bioavailability of the prodrug in the brain. LAT1 has also been studied in neurodevelopment disorders like autism spectrum disorders and Rett syndrome, along with neuropsychiatric implications in depression. Its implications in neuro-oncology, especially in transporting therapeutic agents into cancer cells, show immense future potential. Phenotypes of LAT1 have also shown variations in the general population affecting their ability to respond to painkillers and anti-inflammatory drugs. Furthermore, LAT1-targeted approaches, such as functionalized nanoparticles and prodrugs, show promise in overcoming chemoresistance and enhancing drug delivery to the brain. The ongoing exploration of LAT1’s structural characteristics and therapeutic applications reiterates its critical role in advancing treatments for neurological disorders.
Journal Article
Cymbopogon proximus Chiov’s extract improves insulin sensitivity in rats with dexamethasone-induced insulin resistance and underlying mechanisms
The worldwide prevalence of type 2 diabetes mellitus (T2DM) is increasing swiftly.
Cymbopogon proximus
(
C. proximus
) is a wild herbaceous plant utilized as a potent remedy in Egyptian folk medicine, sometimes referred to as “Halfabar.” This study examined the hypoglycemic, hypolipidemic, and antioxidant properties of the methanolic extract from the aerial parts of
C. proximus
, as well as its impact on pancreatic tumour necrosis factor-α (TNF-α) and Glucose Transporter-4 (GLUT4) in skeletal muscles within an experimental model of insulin resistance. Additionally, bioactive metabolites in the extract were analyzed via liquid chromatography-mass spectrometry (LC/MS) technology. Insulin resistance was induced by administering 1 mg/kg of dexamethasone to rats over a period of 14 days. The rats received two doses of the extract: a low dose of 100 mg/kg body weight and a high dose of 200 mg/kg body weight, along with the reference drug; Metformin (M) at a dose of 40 mg/kg body weight, supplied once daily by gastric tube for 14 days. The treatment of dexamethasone led to a significant (
P
< 0.05) elevation in serum fasting glucose, fasting insulin, HOMA-IR, and pancreatic TNF-α, along with a significant (
P
< 0.05) reduction in GLUT4 expression in skeletal muscles. Both extract and reference treatments significantly (
P
< 0.05) mitigated these abnormalities. The highest dose of the extract exhibited a significantly (
P
< 0.05) greater antioxidant impact, a more pronounced reduction in insulin levels and HOMA-IR, as well as an enhanced rise in GLUT4 expression and insulin sensitivity index compared to the lowest dose and the M. Histopathological and immunohistochemical analyses corroborate the biochemical results. The LC–ESI–MS/MS profiling resulted in the characterization and tentative identification of 95 metabolites’ structures. Identified substances purported to possess anti-diabetic effect include apigenin, luteolin, tricin flavone glycosides, cyanidin, malvidin anthocyanin glycosides, and caffeic acid. These findings suggest that
C. proximus
can mitigate insulin resistance. Additional clinical trials are necessary to validate these findings and assess the extract’s effectiveness in human insulin resistance.
Journal Article