Mobile ad hoc network (MANET) performance is critically affected by the mobility and resource constraints of nodes. Node mobility will impact on connecting stability, and node resource limitations ...will result in congestion, so the development of a routing protocol that promotes quality of service (QoS) in MANET is quite difficult. In particular, frequent interrupting connection may degrade QoS performance in the high-speed node drive scenario, so it is required to build the MANET protocol routing which can be adapted for changes in the networking architecture to support QoS. Moreover, MANET's multipath routing is the most necessary for secure transmission that can be achieved if self-centered nodes in the MANET network are ignored. Secure routing guarantees the reliability of data, confidentiality, authorization and authentication and non-denial. A novel safe multi-way method for dependable data transfer, which depends on the quality of service, is offered in this study. The Ad Hoc on Demand Backward Routing protocol with Optimal Fuzzy Logic (OFL) is also designed to provide multi-path routing. The hybridization of the bat optimization approach provides the optimum route by generating rules in OFL, and hence chooses an optimal rule. The efficiency of the planned technique is evaluated for factors such as final delay, the packet delivery ratio and so on. When the node is 150, the proposed hybrid bat algorithm achieved 0.61 of average packet latency, where the existing technique Particle Swarm Optimization achieved nearly 1.2 to 1.3 packet latency. In this communication network, measurement of packet delivery ratio is an important task for establishing the communication network. The results show that our suggested work has more energy efficiency and network lifetime than existing ones.
This article considers the reception and genre of the Shāhnāmah in India. It takes as its starting-point comments made by the poet Mirza Asad Allah Khan Ghalib in 1866, moving on to look at a Mughal ...Shāhnāmah adaptation, the Tarikh-i dil-gusha-i Shamsher-Khani, and its Urdu translations, as well as other Persian, Urdu and Arabic texts. It investigates the (mis)identification of the Shāhnāmah’s genre, looking at cases in which it was understood as historiographical rather than as a romance, and seeking an explanation for this ‘contamination’ of the sincere genre of history by the mendacious romance genre. A methodological split in the historiographical corpus is proposed, between a rationalist (‘aqli) and transmission-based (naqli) method. The contest between these two methods is considered, and the prevalence of transmission-based history and its similarity to romance is brought forward as a possible reason for the porousness of the border between these ostensibly opposing genres.
The structure–activity relationship study of a diphenylpropanamide series of ROR-γ selective modulators is reported. Compounds were screened using chimeric receptor Gal4 DNA-binding domain (DBD)-NR ...ligand binding domain cotransfection assay in a two-step format. Three different regions of the scaffold were modified to assess the effects on repression of ROR-γ transcriptional activity and potency. The lead compound 1 exhibits modest mouse pharmacokinetics and an acceptable in vitro profile which makes it a suitable in vivo probe to interrogate the functions of ROR-γ in animal models of disease.
The recently discovered apelin/APJ system has emerged as a critical mediator of cardiovascular homeostasis and is associated with the pathogenesis of cardiovascular disease. A role for apelin/APJ in ...energy metabolism and gastrointestinal function has also recently emerged. We disclose the discovery and characterization of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221), a potent APJ functional antagonist in cell-based assays that is >37-fold selective over the closely related angiotensin II type 1 (AT1) receptor.
The recently discovered apelin/APJ system has emerged as a critical mediator of cardiovascular homeostasis and is associated with the pathogenesis of cardiovascular disease. A role for apelin/APJ in energy metabolism and gastrointestinal function has also recently emerged. We disclose the discovery and characterization of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221), a potent APJ functional antagonist in cell-based assays that is >37-fold selective over the closely related angiotensin II type 1 (AT1) receptor. ML221 was derived from an HTS of the ∼330,600 compound MLSMR collection. This antagonist showed no significant binding activity against 29 other GPCRs, except to the κ-opioid and benzodiazepinone receptors (<50/<70%I at 10μM). The synthetic methodology, development of structure–activity relationship (SAR), and initial in vitro pharmacologic characterization are also presented.
NOD1 (nucleotide-binding oligomerization domain 1) protein is a member of the NLR (NACHT and leucine rich repeat domain containing proteins) protein family, which plays a key role in innate immunity ...as a sensor of specific microbial components derived from bacterial peptidoglycans and induction of inflammatory responses. Mutations in NOD proteins have been associated with various inflammatory diseases that affect NF-κB (nuclear factor κB) activity, a major signaling pathway involved in apoptosis, inflammation, and immune response. A luciferase-based reporter gene assay was utilized in a high-throughput screening program conducted under the NIH-sponsored Molecular Libraries Probe Production Center Network program to identify the active scaffolds. Herein, we report the chemical synthesis, structure–activity relationship studies, downstream counterscreens, secondary assay data, and pharmacological profiling of the 2-aminobenzimidazole lead (compound 1c, ML130) as a potent and selective inhibitor of NOD1-induced NF-κB activation.
New optically pure isoxazoline-2-oxide and furan analogs have been synthesized using Pd(0) catalyzed intramolecular cyclizations. Starting from a
meso-diol, optically pure compounds were prepared ...without utilizing chiral ligands at any stage of the synthesis. The stereochemical outcome of the product (>99% ee) was influenced by desymmetrization catalyzed by
Pseudomonas cepacia lipase and the stereoselective nature of the palladium catalyzed transformations.
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Nurr1/NR4A2 is an orphan nuclear receptor transcription factor implicated as a drug target for neurological disorders including Alzheimer’s and Parkinson’s diseases. Previous studies identified ...small-molecule NR4A nuclear receptor modulators, but it remains unclear if these ligands affect transcription via direct binding to Nurr1. We assessed 12 ligands reported to affect NR4A activity for Nurr1-dependent and Nurr1-independent transcriptional effects and the ability to bind the Nurr1 ligand-binding domain (LBD). Protein NMR structural footprinting data show that amodiaquine, chloroquine, and cytosporone B bind the Nurr1 LBD; ligands that do not bind include C-DIM12, celastrol, camptothecin, IP7e, isoalantolactone, ethyl 2-2,3,4-trimethoxy-6-(1-octanoyl)phenylacetate (TMPA), and three high-throughput screening hit derivatives. Importantly, ligands that modulate Nurr1 transcription also show Nurr1-independent effects on transcription in a cell type-specific manner, indicating that care should be taken when interpreting the functional response of these ligands in transcriptional assays. These findings should help focus medicinal chemistry efforts that desire to optimize Nurr1-binding ligands.
A hitherto unknown palladium-catalyzed reaction of nitroalkanes with hydroxy allylic acetates is reported. The reaction led to the formation of γ-nitrocarbonyl compounds instead of the usual ...unsaturated nitroalcohol expected upon displacement of the allylic acetate group.
A hitherto unknown palladium-catalyzed reaction of nitroalkanes with hydroxy allylic acetates is reported. The reaction led to the formation of γ-nitrocarbonyl compounds instead of the usual unsaturated nitroalcohol expected upon displacement of the allylic acetate group.
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