Members Of Class Research Articles

Investigation of the Odilorhabdin Biosynthetic Gene Cluster Using NRPS Engineering.

The recently identified natural product NOSO-95A from entomopathogenic Xenorhabdus bacteria, derived from a biosynthetic gene cluster (BGC) encoding a non-ribosomal peptide synthetase (NRPS), was the first member of the odilorhabdin class of antibiotics. This class exhibits broad-spectrum antibiotic activity and inspired the development of the synthetic derivative NOSO-502, which holds potential as a new clinical drug by breaking antibiotic resistance. While the mode of action of odilorhabdins was broadly investigated, their biosynthesis pathway remained poorly understood. Here we describe the heterologous production of NOSO-95A in Escherichia coli after refactoring the complete BGC. Since the production titer was low, NRPS engineering was applied to uncover the underlying biosynthetic principles. For this, modules of the odilorhabdin NRPS fused to other synthetases were co-expressed with candidate hydroxylases encoded in the BGC allowing the characterization of the biosynthesis of three unusual amino acids and leading to the identification of a prodrug-activation mechanism by deacylation. Our work demonstrates the application of NRPS engineering as a blueprint to mechanistically elucidate large or toxic NRPS and provides the basis to generate novel odilorhabdin analogues with improved properties in the future.

Preparation and Evaluation of Ranitidine Hydrochloride Floating Microspheres

<i>Introduction</i>: Ranitidine hydrochloride, a member of the H2-receptor antagonist class, is widely employed in treating gastrointestinal conditions like ulcers, gastroesophageal reflux disease (GERD) and Zollinger-Ellison syndrome by reducing gastric acid production. Microspheres, designed for extended drug delivery and enhanced bioavailability, were formulated and evaluated in this study. <i>Aim</i>: To develop ranitidine hydrochloride microspheres capable of prolonging drug delivery and improving bioavailability. Methods: The inotropic gelation method was utilized to prepare alginate microspheres incorporating polymers such as ethyl cellulose, sodium carboxymethyl cellulose, HPMC, and carbopol®. The resulting drug-loaded microspheres exhibited spherical rigidity after cross-linking with a 10% w/v calcium chloride solution. Evaluation parameters including Fourier transform infra-red (FTIR) analysis, precompression characteristics, percentage yield, swelling index, and drug content were determined. <i>Results</i>: The FTIR results obtained, showed there was no incompatibility among the excipients and the active pharmaceutical ingredient. The Scanning electron microscopy (SEM) obtained, indicated the presence of spherical particles present in the formulation. The pre-compression evaluation showed that the angle of repose ranged from 4.85 ± 0.02 to 7.22 ± 0.06o for batched F4 and F1 respectively, while the Carr’s index ranged from 73.5 ± 2.47% to 87.00 ± 3.53% for batches F-7 and F-1 respectively. The percentage yield ranged from 73.5 ± 2.47% to 87.00 ± 3.53% for batches F-7 and F-1 respectively. <i>In vitro</i> drug release studies revealed sustained drug release over 4 hours, with a maximum release of 69.50 ± 1.77% observed for batch F-1. <i>Conclusion</i>: Overall, the formulated ranitidine hydrochloride microspheres demonstrated prolonged and controlled release characteristics, indicating their potential for use in controlled drug delivery applications.

Enrofloxacin Pharmaceutical Formulations through the Polymer-Free Electrospinning of β-Cyclodextrin-oligolactide Derivatives.

Enrofloxacin (ENR), a member of the fluoroquinolone class of antibiotics, is widely used in veterinary medicine to treat bacterial infections. Like many antibiotics, ENR has limited water solubility and low bioavailability. To address these challenges, drug formulations using solid dispersions, nanosuspensions, surfactants, cocrystal/salt formation, and inclusion complexes with cyclodextrins may be employed. The approach described herein proposes the development of ENR formulations by co-electrospinning ENR with custom-prepared cyclodextrin-oligolactide (CDLA) derivatives. This method benefits from the high solubility of these derivatives, enabling polymer-free electrospinning. The electrospinning parameters were optimized to incorporate significant amounts of ENR into the CDLA nanofibrous webs, reaching up to 15.6% by weight. The obtained formulations were characterized by FTIR and NMR spectroscopy methods and evaluated for their antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. This study indicates that the presence of CDLA derivative does not inhibit the antibacterial activity of ENR, recommending these formulations for further development.

Public attitudes to China in the ‘Five Eyes': unpacking views across the Anglosphere security community

ABSTRACT China is an important security concern for the United States and its allies, including the Five Eyes intelligence-sharing group that is sometimes described as the core of the ‘Anglosphere’ security community. While we would expect securitising discourses at the elite level to reproduce some common perceptions of China, to what extent are attitudes to China shared across the publics in these countries? In this article, we unpack public attitudes towards China in the United States, the United Kingdom, Canada, Australia, and New Zealand. Drawing on the results of public opinion surveys we conducted in 2022, we note areas of similarity and divergence then drill down into the drivers of public attitudes. We show that even though aggregate attitudes towards China in the five countries appear to align with official security discourses, this hides significant variation in how different groups within these societies view China. In particular, ethnic minorities and recent immigrants, along with members of higher socio-economic classes, urban residents, and young people, tend to be more positive towards China. Our findings bring new insights into the potency of government-driven securitisation, particularly in terms of identifying groups within societies that are less inclined to follow their government’s view of China.

The Chemistry of Angucyclines.

Angucyclines and angucyclinones represent a class of natural compounds that belong to the group of aromatic polyketides. They exhibit a wide array of biological properties, such as antimicrobial, antiviral, and cytotoxic. Their considerable therapeutic potential and diverse scaffolds have attracted many synthetic chemists to devise novel strategies to construct their intricate molecular architecture. Over 300 class members have been isolated from natural sources, mainly from bacterial strains of Streptomyces species. This review highlights recent advancements in their synthesis, such as oxidative cyclization, photooxidation, and metal-catalyzed [4+2]-cycloaddition, which has facilitated the efficient and practical total syntheses of various angucycline and angucyclinone natural products.

Engineering of Rieske dioxygenase variants with improved cis-dihydroxylation activity for benzoates.

Rieske dioxygenases have a long history of being utilized as green chemical tools in the organic synthesis of high-value compounds, due to their capacity to perform the cis-dihydroxylation of a wide variety of aromatic substrates. The practical utility of these enzymes has been hampered however by steric and electronic constraints on their substrate scopes, resulting in limited reactivity with certain substrate classes. Herein, we report the engineering of a widely used member of the Rieske dioxygenase class of enzymes, toluene dioxygenase (TDO), to produce improved variants with greatly increased activity for the cis-dihydroxylation of benzoates. Through rational mutagenesis and screening, TDO variants with substantially improved activity over the wild-type enzyme were identified. Homology modeling, docking studies, molecular dynamics simulations, and substrate tunnel analysis were applied in an effort to elucidate how the identified mutations resulted in improved activity for this polar substrate class. These analyses revealed modification of the substrate tunnel as the likely cause of the improved activity observed with the best-performing enzyme variants.

Class Symbolic Regression: Gotta Fit ’Em All

We introduce “Class Symbolic Regression” (Class SR), the first framework for automatically finding a single analytical functional form that accurately fits multiple data sets—each realization being governed by its own (possibly) unique set of fitting parameters. This hierarchical framework leverages the common constraint that all the members of a single class of physical phenomena follow a common governing law. Our approach extends the capabilities of our earlier Physical Symbolic Optimization (Φ-SO) framework for symbolic regression, which integrates dimensional analysis constraints and deep reinforcement learning for unsupervised symbolic analytical function discovery from data. Additionally, we introduce the first Class SR benchmark, comprising a series of synthetic physical challenges specifically designed to evaluate such algorithms. We demonstrate the efficacy of our novel approach by applying it to these benchmark challenges and showcase its practical utility for astrophysics by successfully extracting an analytic galaxy potential from a set of simulated orbits approximating stellar streams.

Deriving the new cotangent Fréchet distribution with real data analysis

This study introduces the family of the novel ”cot-generator” distributions based on the cotangent function. The construction of the probability density function based on the cot-generator and its corresponding moments, reliability indicators, and order statistics are derived. Regarding inferential procedures, the maximum likelihood estimation method is implemented to estimate the model parameters in a non-closed form. The novel Cot-Fréchet distribution (NCFD) is then focused on a specific class member, constructed using the Fréchet distribution as the baseline. The estimators’ bias, variance, and mean square error (MSE) efficiency are examined and evaluated through Monte Carlo simulation experiments. The novel model is also applied to some real data sets to assess its efficacy and is compared with other competing distributions.

The nested structures of higher-order interactions promote the cooperation in complex social networks

As a powerful tool for exploring non-pairwise interactions, higher-order networks deepen our understanding of how cooperation emerges in complex systems. However, nearly all researches concerning the cooperative evolution on higher-order networks have neglected the prevalence of nested structures in real-world interactions — for instance, students are members of classes, which are components of grades, and these grades, in turn, are part of schools and so on. In this paper, we propose a general and scalable method to investigate the influence of nested structures in higher-order interactions on group cooperation. Specifically, by adjusting the proportion of lower-order nested relations (e.g., pairwise links) within higher-order structures, we find that higher-order interactions are more favorable to the cooperation if they comprise a rich nested dyadic structure. In addition, for the first time, we introduce higher-order network motifs to examine the contributions of various nested structures to cooperation. It is interesting to observe that the more uniform the nested structure, the more it promotes the cooperation. Our study offers a novel perspective to examine the evolution of cooperative behaviors in more complex realistic systems.

Dynamic threshold spiking neural P systems with weights and multiple channels

Membrane computing represents a sophisticated branch of computational science that assimilates the characteristics of cellular membranes and harnesses mathematical principles. It derives inspiration from the intricate structure and functional attributes exhibited by biological cell membranes. This exposition is dedicated to an in-depth exploration of spiking neural P systems (SN P systems), meticulously crafted to emulate the intricate signaling and interaction phenomena between cellular entities. Nevertheless, conventional spiking neural P systems confront inherent constraints pertaining to their excitation rules, which hinder their applicability to real-world challenges. In pursuit of overcoming these limitations, we introduce a novel paradigm encompassing the dynamic thresholds, synaptic weights, and the integration of multiple channels within synapses. This innovative framework culminates in the dynamic threshold spiking neural P systems with weights of synapses and multiple channels in synapses (DSNP-WM systems). It is noteworthy that DSNP-WM systems demonstrate Turing universality, effectively functioning as versatile entities capable of both number generation and acceptance, in addition to performing intricate computations. Importantly, these systems showcase the efficiency in tackling challenges posed by semi-uniform solutions, exemplified by the Subsets Sum problem—a fundamental member of the NP-complete problem class, which employs a nondeterministic approach.

Toussaint Louverture and the Undermining of the Haitian Revolution

This work using a structurationist, structural Marxist, phenomenological structuralism, understanding of practical consciousness constitution, explores the origins and basis for the Haitian Revolutionary leader, Toussaint Louverture’s (May 20, 1743-April 1, 1803), social, political, and economic policies. The eldest son of an Arada King, Toussaint Louverture, was a creole-slave born on the island of Saint-Domingue/Haiti. As the eventual leader of the Revolution from 1794-1801, Louverture attempted to have the island remain an independent French territory where slavery was outlawed, but the export-oriented plantation economy, with the slave trade, persisted. He, essentially, adopted the position of the French Royalists, the white plantation owners who wanted more autonomy from France and its “exclusif” mercantile economic system, which forced them to trade and do business exclusively with French merchants and bankers. Although, Louverture’s demeanor and position is typically juxtaposed against his successor, Jean-Jacques Dessalines, all subsequent leaders, I argue here, would go on to adopt Louverture’s policies, the export-oriented agricultural economy, with variations based on who (mulattoes or members of the black grandon class) should serve in the position of the white planters once independence was declared from France in 1804. This decision, to maintain Louverture’s political and economic policies as opposed to redistributing the land to the African masses so that they can pursue their subsistence agriculture and komes, I conclude, has undermined the Revolutionary impetus of the Haitian Revolution and converted Haiti into the so-called poorest (periphery) country in the Western Hemisphere.

Solving the Travelling Salesman Problem Using the PSO Optimization

This article examines a potential solution to the well-known Travelling Salesman Problem (TSP), which is classified as an NP-hard problem. We also provide a theoretical synopsis of several approaches that have been employed to tackle this problem. A prominent example of a combinatorial problem is the traveling salesman problem (TSP). To address the fundamental PSO algorithm's premature convergence issue and stagnation behavior on TSP, a scout characteristic-based PSO algorithm is suggested.We address Particle Swarm Optimization (PSO), a member of the evolutionary methods class, and outline the methodology for applying PSO to the TSP. Among population-based metaheuristic optimization methods, Particle Swarm Optimization (PSO) is one of the most widely used. Scientific domains such as engineering, chemistry, medicine, advanced physics, and humanities have all effectively employed PSO. Numerous theoretical and empirical results on the convergence and parameterization of PSO versions have been produced as a result of the method's extensive investigation since its introduction in 1995. Hundreds of PSO versions have been developed. It is well recognized that population size has a significant impact on the effectiveness of metaheuristics; nevertheless, no comprehensive research has been done on the appropriate selection of PSO swarm size to date.Through the application of this approach, we examine the effects of various control settings. The ideal solution and the quality of the solution are contrasted.

Universal Ideational Warfare: Preemptive Ideocide in the Global South

Abstract The world is entering a post-universal historical conjuncture marked by a “great divergence” triggered by a paroxysm of crises exacerbated by the Western world’s reluctance to accept its diminishing global role. In a panic response, the West is consolidating itself into a Euro-American Confederal Empire, engaging in a form of universal ideational warfare against emerging civilization-states in an effort to maintain its civilizational hegemony. This has resulted in an ideological engineering contest within the global public sphere pursued through the practice of “preemptive ideocide,” which seeks to perpetuate a missionary universalism that imposes Western political-cultural norms upon the world’s divergent cultural and self-governing modes of existence. This ideational warfare is situated within an emergent Cold War Two. The protagonists of this ideational warfare represent a service class of ideocrats devoted to the preservation of Western global primacy. The article highlights the key themes addressed by members of this service class who act as an elite posse of a global thought police. In conclusion, the article argues that humanity is irreversibly divided into non-convergent but non-conflictual cultural identities and proposes the adoption in the Global South of a cultural polygenesis covenant as an exit strategy from the prevailing dependency on missionary universalism’s ideational framework.

The Fav-Jerry Distribution: Another Member in the Lindley Class with Applications

In this paper, we designed another one-parameter distribution using a mixture of exponential and gamma distributions. This new distribution is unique among other members of the Lindley class because the qunatile function has a closed-functional form hence lending itself to analytical study. This distribution is named Fav-Jerry after the names of the authors. The statistical properties and point estimation using some non-Bayesian methods were studied. We deploy tow real datasets to demonstrate the usefulness of the new model. The real data applications using data sets on mortality rate and failure rate in a particular airplane showed that the proposed model fits well compared to its competitors, therefore, the Fav-Jerry distribution is superior to Two parameter Chris-Jerry(TPCJ), Chris-Jerry, Exponentiated Inverted Exponential distribution, and Weibull distributions and then parametric plots showing the histogram, CDF, survival and TTT plots gotten from both data sets are displayed.

Effect of White Rice Flour in the Formulation Development and Evaluation of Sumatriptan Succinate Floating Microspheres by Modified Emulsion Solvent Diffusion Method

A sustained release system for Sumatriptan designed to increase its residence time in the stomach without contact with the Microspheres was achieved through the preparation of floating Microspheres by the Modified Emulsion solvent Diffusion method. In the present study attempt has been made to develop sustained released drug delivery system by formulating the floating Microspheres of Sumatriptan using White Rice Flour powder as a natural polymer which is biodegradable, biocompatible, nontoxic, economically cheap cost, devoid of adverse and side effects and easily availability. Sumatriptan Succinate is the succinate salt form of sumatriptan, a member of the triptan class of compounds with anti-migraine property. Sumatriptan succinate selectively binds to and activates serotonin 5-HT1 receptors. The 12 batches of floating Microspheres (MF1 to MF12) were formulated by Modified Emulsion solvent Diffusion method using different ratio of polymers like White Rice Flour power, HPMC K4M and Carbopol. The formulated Microspheres were evaluated by means of different parameters like shape and density of Microsphere, drug content uniformity, In-vitro buoyancy, swelling Index, In-vitro dissolution studies. The formulation MF6 has better sustained release when compared other formulations, hence we conclude that the combination of White Rice Flour powder, HPMC K4M shows better Gastric retention time which sustains the release of the dosage form.

Spectroscopic survey of faint planetary-nebula nuclei

We present spectroscopy of three hydrogen-deficient central stars of faint planetary nebulae, with effective temperatures (Teff) in excess of 100 000 K. The nucleus of RaMul 2 is a Population II Wolf-Rayet star of spectral type [WC], and the central stars of Abell 25 and StDr 138 are two new members of the PG1159 class. Our spectral analyses reveal that their atmospheres have a similar chemical composition. They are dominated by helium and carbon, which was probably caused by a late helium-shell flash. Coincidentally, the three stars have similar masses of about M = 0.53 M⊙ and hence form a post-asymptotic giant branch (AGB) evolutionary sequence of an initially early-K-type main sequence star with M = 0.8 M⊙. The central stars cover the period during which the luminosity fades from about 3000 to 250 L⊙ and the radius shrinks from about 0.15 to 0.03 R⊙. The concurrent increase of the surface gravity during this interval from log g = 5.8 to 7.2 causes the shutdown of the stellar wind from an initial mass-loss rate of log Ṁ/(M⊙ yr−1) = −6.4, as measured for the [WC] star. Along the contraction phase, we observe an increase in Teff from 112 000 K, marked by the [WC] star, to the maximum value of 140 000 K, and a subsequent cooling to 130 000 K, marked by the two PG1159 stars.

Review Paper on Models for CNS Stimulant Drug Screening

Drugs called central nervous system (CNS) stimulants hasten both mental and physical functions. Narcolepsy and new born apnea are two disorders characterised by a lack of adrenergic stimulation that are treated with central nervous system stimulants. Moreover, the paradoxical effects of dextroamphetamine sulphate (Dexedrine) and methylphenidate (Ritalin) on attention-deficit hyperactivity disorder are invoked to justify their use (ADHD). The majority of CNS stimulants mimic the classic "fight or flight" condition linked to sympathetic nervous system activation and are chemically comparable to the neurohormone norepinephrine. The xanthines, including theophylline, and caffeine are more intimately connected to one another. A few more CNS stimulant class members do not belong to any particular chemical classes. A detailed analysis of CNS stimulant medications, their mechanisms of action, and in vivo CNS stimulant models is provided in the review on central nervous system stimulants.

Comparative genomic analysis of Planctomycetota potential for polysaccharide degradation identifies biotechnologically relevant microbes

BackgroundMembers of the Planctomycetota phylum harbour an outstanding potential for carbohydrate degradation given the abundance and diversity of carbohydrate-active enzymes (CAZymes) encoded in their genomes. However, mainly members of the Planctomycetia class have been characterised up to now, and little is known about the degrading capacities of the other Planctomycetota. Here, we present a comprehensive comparative analysis of all available planctomycetotal genome representatives and detail encoded carbohydrolytic potential across phylogenetic groups and different habitats.ResultsOur in-depth characterisation of the available planctomycetotal genomic resources increases our knowledge of the carbohydrolytic capacities of Planctomycetota. We show that this single phylum encompasses a wide variety of the currently known CAZyme diversity assigned to glycoside hydrolase families and that many members encode a versatile enzymatic machinery towards complex carbohydrate degradation, including lignocellulose. We highlight members of the Isosphaerales, Pirellulales, Sedimentisphaerales and Tepidisphaerales orders as having the highest encoded hydrolytic potential of the Planctomycetota. Furthermore, members of a yet uncultivated group affiliated to the Phycisphaerales order could represent an interesting source of novel lytic polysaccharide monooxygenases to boost lignocellulose degradation. Surprisingly, many Planctomycetota from anaerobic digestion reactors encode CAZymes targeting algal polysaccharides – this opens new perspectives for algal biomass valorisation in biogas processes.ConclusionsOur study provides a new perspective on planctomycetotal carbohydrolytic potential, highlighting distinct phylogenetic groups which could provide a wealth of diverse, potentially novel CAZymes of industrial interest.

Straightforward Synthesis of 1‐Aryloxy‐1,1‐difluoro‐3‐aminopropan‐2‐ols – Accessing Fluorinated Derivatives of Commercialized Beta‐Blockers

The efficient synthesis of an array of 1‐aryloxy‐1,1‐difluoro‐3‐aminopropan‐2‐ols in a one‐pot epoxidation/nucleophilic ring‐opening via the corresponding iodohydrines is described. This methodology permits the construction of 1,1‐difluorinated derivatives of commercialized beta‐blockers in addition to unprecedented members of this compound class.

Spectroscopic Survey of Faint Planetary-nebula Nuclei. IV. The A35-type Central Star of Pa 27* *Based on observations obtained with the Hobby–Eberly Telescope (HET), which is a joint project of the University of Texas at Austin, the Pennsylvania State University, Ludwig-Maximillians-Universität München, and Georg-August Universität Göttingen. The HET is named in honor of its principal benefactors, William P. Hobby and Robert

We present optical spectroscopy of the 12th-magnitude central star of the planetary nebula (PN) Patchick 27 (Pa 27), obtained during a survey of faint PN nuclei (PNNs) with the Low-Resolution Spectrograph of the Hobby–Eberly Telescope. The optical spectrum of Pa 27 is that of a K0 III red giant with rotationally broadened lines. However, the star is detected in the near-ultraviolet (near-UV) with GALEX, showing that a hot binary component is also present. The spectral-energy distribution from the near-UV to the mid-infrared can be fitted with a combination of the K0 III giant and a hot PNN with an effective temperature of about 50,000 K. Photometric observations of Pa 27, both ground-based and from TESS, show a low-amplitude sinusoidal variation with a period of 7.36 days, probably due to starspots on a rotating and magnetically active cool giant. Pa 27 is a new member of the rare class of “A35-type central stars,” which are binary PNNs consisting of a spotted late-type star and a hot pre–white dwarf. They are likely the result of a situation where an asymptotic-giant-branch (AGB) star ejects its outer layers in a dense wind, part of which is captured by a distant companion, spinning up its rotation by accretion of material and angular momentum. We suggest several useful follow-up observations.