Alternative Route Research Articles

Potentiation of Catalase-Mediated Plant Thermotolerance by N-Terminal Attachment of Solubilizing/Thermostabilizing Fusion Partners

Catalase (CAT) plays a crucial role in plant responses to environmental stresses and maintaining redox homeostasis. However, its putative heat lability might compromise its activity and function, thus restricting plant thermotolerance. Herein, we verified Arabidopsis CAT3 was of poor thermostability that was then engineered by fusion expression in Escherichia coli. We found that our selected fusion partners, three hyperacidic mini-peptides and the short rubredoxin from hyperthermophile Pyrococcus furiosus, were commonly effectual to enhance the solubility and thermostability of CAT3 and enlarge its improvement on heat tolerance in E. coli and yeast. Most importantly, this finding was also achievable in plants. Fusion expression could magnify CAT3-mediated thermotolerance in tobacco. Under heat stress, transgenic lines expressing CAT3 fusions generally outperformed native CAT3 which in turn surpassed wild-type tobacco, in terms of seed germination, seedling survival, plant recovery growth, protection of chlorophyll and membrane lipids, elimination of H2O2, as well as mitigation of cell damage in leaves and roots. Moreover, we revealed that the introduced CAT3 or its fusions seemed solely responsible for the enhanced thermotolerance in tobacco. Prospectively, this fusion expression strategy would be applicable to other crucial plant proteins of intrinsic heat instability and thus provide an alternative biotechnological route for ameliorating plant heat tolerance.

A Neural Phillips Curve and a Deep Output Gap

Many problems plague empirical Phillips curves (PCs). Among them is the hurdle that the two key components, inflation expectations and the output gap, are both unobserved. Traditional remedies include proxying for the absentees or extracting them via assumptions-heavy filtering procedures. I propose an alternative route: a Hemisphere Neural Network (HNN) whose architecture yields a final layer where components can be interpreted as latent states within a Neural PC. First, HNN conducts the supervised estimation of nonlinearities that arise when translating a high-dimensional set of observed regressors into latent states. Second, forecasts are economically interpretable. Among other findings, the contribution of real activity to inflation appears understated in traditional PCs. In contrast, HNN captures the 2021 upswing in inflation and attributes it to a large positive output gap starting from late 2020. The unique path of HNN’s gap comes from dispensing with unemployment and GDP in favor of an amalgam of nonlinearly processed alternative tightness indicators.

Research agenda for ending preventable maternal deaths from postpartum haemorrhage: a WHO research prioritisation exercise

IntroductionPostpartum haemorrhage (PPH) remains the leading cause of maternal death. Yet there is a lack of clarity around what research is needed to determine what works and how best to...

Quadratic Cascading in Quasi-Phase-Matching: An Alternative Route to Efficient Third-Harmonic Generation

We report on the theoretical/numerical investigation of simultaneous second- and third-harmonic generation from a single wavelength input in quasi-phase-matched crystals. The presented technique consists of a quadratic crystal with two first-order quasi-phase-matched sections: one designed for quasi-phase-matching to second-harmonic generation and the other for quasi-phase-matching to third-harmonic generation via sum-frequency generation. We identify an optimal length ratio (optimal number of domains) for these sections in order to enhance the conversion to the third harmonic, achieving nearly complete energy transfer. The advantages of the method are demonstrated both numerically and analytically, with a specific example using periodically poled lithium niobate. Quadratic cascading with quasi-phase-matching proves to be an effective approach for achieving cubic-like effects with high conversion efficiencies.

Solving blockage problem of the 5G mmWaves Wireless Communications using Jellyfish Search Optimizer

The 5G technologies are aimed to support a variety of vertically connected applications with heterogeneous devices and machines with significant improvements in terms of higher quality of service, increased network capacity and improved system throughput. However, 5G systems still face a number of challenges mentioned by researchers and organizations, and among these challenges, we highlight that millimeter wave links are very susceptible to blockage. If the line-of-sight communication path is blocked, reflexive path communication can help maintain communication. The shortest route was to take an alternate route when the first route was blocked. Among the proposed solutions to the blocking problem is an algorithm to distribute the power between different mmWave communication paths in order to overcome the masses of links under randomly distributed obstacles. The problem has been resolved with an exact method. In this article, we have optimized all the results of this exact method by applying a powerful metaheuristic technique called jellyfish search optimizer to maximize the overall capacity of the path between two nodes. The results showed that our approach procures an improvements exceed 100% over the results of the exact method.

Evolucollateral dynamics in stroke: Evolutionary pathophysiology, remodelling and emerging therapeutic strategies.

Leptomeningeal collaterals (LMCs) are crucial in mitigating the impact of acute ischemic stroke (AIS) by providing alternate blood flow routes when primary arteries are obstructed. This article explores the evolutionary pathophysiology of LMCs, highlighting their critical function in stroke and the genetic and molecular mechanisms governing their development and remodelling. We address the translational challenges of applying animal model findings to human clinical scenarios, emphasizing the need for further research to validate emerging therapies-such as pharmacological agents, gene therapy and mechanical interventions-in clinical settings, aimed at enhancing collateral perfusion. Computational modelling emerges as a promising method for integrating experimental data, which requires precise parameterization and empirical validation. We introduce the 'Evolucollateral Dynamics' hypothesis, proposing a novel framework that incorporates evolutionary biology principles into therapeutic strategies, offering new perspectives on enhancing collateral circulation. This hypothesis emphasizes the role of genetic predispositions and environmental influences on collateral circulation, which may impact therapeutic strategies and optimize treatment outcomes. Future research must incorporate human clinical data to create robust treatment protocols, thereby maximizing the therapeutic potential of LMCs and improving outcomes for stroke patients.

Applying Topological Information for Routing Commercial Vehicles Around Traffic Congestion

The growth of urbanization, population, and economic activity has led to a substantial increase in freight transportation demand, exceeding the capacity of existing infrastructure and creating new challenges across various regions. This has resulted in significant traffic congestion, increased travel times, and higher operational costs for commercial vehicle fleets. Leveraging topological data, such as road networks and traffic patterns, can enable more efficient routing strategies to navigate around congested areas. This study presents a comprehensive approach to truck rerouting strategy by integrating spatial analysis, truck characteristics, traffic conditions, road geometry, and cost–benefit analysis to select alternative routes suitable for commercial vehicle fleets. Incorporating real-time traffic information and predictive analytics, commercial vehicle operators can optimize their routes, reduce fuel consumption, and improve overall delivery efficiency. Three case studies were presented to demonstrate the proposed diversion decision framework. Two scenarios were designed for each case study: a base scenario with no diversion and an optimized scenario with a diversion strategy. The travel times, fuel consumption, and economic impacts between the two scenarios were compared and quantified as a total annual saving of USD 52 million. This approach goes beyond selecting alternative routes and provides decision makers with measurable benefits that justify diversion strategies.

Development of Nanocomposite Microspheres for Nasal Administration of Deferiprone in Neurodegenerative Disorders

Elevated brain iron levels are characteristic of many neurodegenerative diseases. As an iron chelator with short biological half-life, deferiprone leads to agranulocytosis and neutropenia with a prolonged therapeutic course. Its inclusion in sustained-release dosage forms may reduce the frequency of administration. On the other hand, when administered by an alternative route of administration, such as the nasal route, systemic exposure to deferiprone will be reduced, thereby reducing the occurrence of adverse effects. Direct nose-to-brain delivery has been raised as a non-invasive strategy to deliver drugs to the brain, bypassing the blood–brain barrier. The aim of the study was to develop and characterize nanocomposite microspheres suitable for intranasal administration by combining nano- and microparticle-based approaches. Nanoparticles with an average particle size of 213 ± 56 nm based on the biodegradable polymer poly-ε-caprolactone were developed using the solvent evaporation method. To ensure the deposition of the particles in the nasal cavity and avoid exhalation or deposition into the small airways, the nanoparticles were incorporated into composite structures of sodium alginate obtained by spray drying. Deferiprone demonstrated sustained release from the nanocomposite microspheres and high iron-chelating activity.

LY354740, an agonist of glutamatergic metabotropic receptor mGlu2/3 increases the cytochrome P450 2D (CYP2D) activity in the frontal cortical area of rat brain.

Our previous studies indicated that changes in the functioning of the brain glutamatergic system involving the NMDA receptor may affect cytochrome P450 2D (CYP2D) in the brain. Since CYP2D may contribute to the metabolism of neurotransmitters and neurosteroids engaged in the pathology and pharmacology of neuropsychiatric diseases, in the present work we have investigated the effect of compound LY354740, an agonist of glutamatergic metabotropic receptor mGlu2/3, on brain and liver CYP2D. The activity (high performance liquid chromatography with fluorescence detection) and protein levels (Western blotting) of CYP2D were measured in the microsomes from the liver and different brain areas of male Wistar rats after 5day-treatment with LY354740 (10mg/kg ip). The results were analyzed statistically using Student's t-test. Among the investigated brain areas, the highest CYP2D activity was found in the cerebellum and brainstem, which exceeded that in the thalamus, cortex, hippocampus and frontal cortex. The mGlu2/3 receptor agonist LY354740 administered for five consecutive days significantly increased the protein level and activity of CYP2D in the frontal cortex. Such a tendency was also observed in the other brain areas. LY354740 did not affect the CYP2D activity in the liver. Repeated administration of the mGlu2/3 receptor agonist, the compound LY354740 specifically increases the protein level and activity of CYP2D in the frontal cortex, which may accelerate dopamine synthesis via an alternative CYP2D-mediated route in the mesocortical dopaminergic pathway, and thus may contribute to the beneficial pharmacological effect on negative symptoms of schizophrenia.

Evaluating N-acetylcysteine as a Protective Agent Against Chemotherapy-induced Neuropathy in Breast Cancer: A Triple-blind, Randomized Clinical Trial.

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant clinical issue that affects patients' quality of life and can limit the dosing of chemotherapeutic agents. N-acetylcysteine (NAC) has been proposed as a potential chemoprotective agent against CIPN due to its antioxidant properties. This study aimed to investigate the efficacy of oral NAC in preventing and controlling taxane-induced neuropathy in patients with breast cancer. This randomized, triple-blind, placebo-controlled trial included 80 breast cancer patients undergoing taxane-based chemotherapy. Participants were divided into 2 groups: an intervention group receiving 1200mg of oral NAC in divided doses per day and a placebo group. Patients were evaluated for neuropathy grade and functional status at 1 and 12 weeks postintervention. Our analysis revealed no significant difference in the incidence and severity of neuropathy between the intervention and placebo groups at 1 (P=0.328) and 12 weeks (P=0.569) postchemotherapy. Baseline characteristics such as age, number of treatment cycles, and disease stage were similar between groups, indicating a homogeneous population. Oral NAC at a dose of 1200mg per day did not significantly reduce the incidence or severity of taxane-induced neuropathy. These findings suggest that the oral bioavailability of NAC may be insufficient to exert a protective effect and that future studies should consider alternative dosing strategies or routes of administration. The need for further research to optimize NAC's chemoprotective role in CIPN remains evident.

Marketing a culture of achievement to Black and Brown students: TNTP and neoliberal multiculturalism

ABSTRACT Neoliberal multiculturalism is a global racialization process that works as a unifying discourse for the rationalization of neoliberal policies within U.S. global ascendancy and capitalist development. Invoking state multiculturalism, e.g. ‘diversity’ or ‘equity’, neoliberal multiculturalism is officially antiracist. Official antiracism portrays multiculturalism as being at its core while limiting discussions of race and racism to sanctioned racial discourses. Using neoliberal multiculturalism as a framework, this paper presents a critical analysis of the racial ideology presented in TNTP’s founding teacher training curriculum designed specifically for its Teaching Fellows. The analysis demonstrates how official antiracism can function in curriculum designed to train fast-tracked selective alternative route program teachers to teach predominantly Black, Latino, and immigrant students in lower-income neighborhood public schools.

A Pharmacokinetic and Bioavailability Study of Ecklonia cava Phlorotannins Following Intravenous and Oral Administration in Sprague–Dawley Rats

This study examines the pharmacokinetics and bioavailability of phlorotannins from Ecklonia cava in rats following intravenous and oral administration. Known for their potent antioxidant, anti-inflammatory and many other bioactivities, these phlorotannins, particularly dieckol, 8,8′-bieckol, and phlorofucofuroeckol-A (PFF-A), were analyzed using high-performance liquid chromatography coupled with tandem mass spectrometry. Intravenous administration at 10 mg/kg allowed detectability in plasma for up to 36 h for dieckol and 8,8′-bieckol, but only 2 h for PFF-A. Oral administration at doses of 100 mg/kg and 1000 mg/kg showed limited detectability, indicating low bioavailability and rapid clearance, particularly for PFF-A. The pharmacokinetic data suggest non-linear increases in the maximum plasma concentration (Cmax) and area under the curve (AUC) with increasing doses, pointing to significant challenges in achieving systemic availability of these eckols through oral administration. This study underscores the necessity for advanced formulation strategies and alternative routes of administration to enhance systemic bioavailability. At the same time, this result also suggests their effects may be through non-systemic pathways such as gut microbiome modulation or lipid-rich tissue targeting. The findings lay a crucial foundation for the further development of Ecklonia cava phlorotannins as therapeutic agents, offering insights into their pharmacokinetic behavior and informing enhancements in future clinical utility.

Bimodal Droplet-Based Electricity Generation Through Semi Cassini Oval Dynamic Morphology Control.

Droplet-based electricity generator (DEG) is the promising energy harvesting technology applicable in versatile scenarios. Despite numerous optimizations in DEG's materials and structures, few has paid attention to the droplet dynamics and morphology control. Here the droplet's spread-retraction dynamics and the resultant semi Cassini oval (SCO) morphology are reported, characterized by convex at both ends and concave in the middle. The lifted top electrode (LTE) is designed to respond to the dynamic SCO morphology in two steps: 1) LTE first contacts the leading edge of the spreading droplet, generating a negative voltage peak; 2) LTE second contacts the trailing edge of the retracting droplet, generating a positive voltage peak. In this way, bimodal electrical output is obtained, which exhibits 25% increase in peak-to-peak voltage and 33% increase in average power compared to the traditional DEG with only one voltage peak. These results prove that incorporating the droplet dynamics and morphology control into DEG design uplifts the energy harvesting limit from individual droplet. The proposed LTE-DEG inspires alternative route for DEG power enhancement by maximizing energy utilization of individual droplet from the perspective of droplet dynamic morphology design.

Impact of the K and Fe insertion methods in KFeCeZr catalysts on the CO2 hydrogenation to C2/C3 olefins at room pressure

Light olefins, traditionally sourced from petroleum, are currently being investigated through alternative routes, such as CO2 hydrogenation, aligning with CCUS policies. Alkali-promoted Fe-based catalysts have shown promise in coupling reverse water–gas shift and Fischer-Tropsch processes to produce light olefins from CO2 directly. The in-situ generated Fe5C2 phase is commonly associated with the high activity of these catalysts. However, the preparation methods employed can lead to distinct catalyst properties, which considerably impact the performance during the reaction. Here, we investigate different strategies to introduce K and Fe in the KFeCeZr system and correlate catalyst properties with catalytic activity during CO2 hydrogenation at ambient pressure. The catalyst prepared by one-pot precipitation of Fe, Ce, and Zr followed by K impregnation showed the most promising results in terms of conversion and productivity of light olefins. The effective incorporation of Fe in the CeZrOx structure during synthesis was essential for maintaining the high dispersion of metallic Fe particles after reduction, improving reactant chemisorption. Under reaction conditions, this catalyst showed the most remarkable propensity to form iron carbides (FexCy), mainly composed of Fe5C2 phase. In general, this work highlights the impact that the construction steps of a multifunctional catalyst have on the physicochemical properties and, consequently, on the catalytic activity.

Enhancing cross-domain recommendations: Leveraging personality-based transfer learning with probabilistic matrix factorization

The conventional method of computing personality scores through extensive questionnaire-based surveys poses practical challenges in real-world scenarios. An alternate route is to predict personality scores from user reviews by analyzing various linguistic features such as writing style, word choices, and specific phrases. However, the reviews are domain-dependent and classification models trained on one domain cannot be readily applied to other domains. To mitigate this challenge, we propose a cross-domain recommendation framework called PEMF-CD which leverages a novel mixing strategy to integrate user reviews from multiple domains with common joint embedding space and predict user personality scores using a transformer model. By capturing the underlying semantics and latent representations within the textual data, the transformer architecture can effectively model the linguistic cues to infer users’ personality traits, and the learning is transferred across domains. To further enhance the recommendation process, our model integrates personality-wise and rating pattern-based similarities of users into a probabilistic matrix factorization method that fosters user neighborhoods based on similarity scores among users. Comprehensive experiments were conducted using five real-world datasets from TripAdvisor and Amazon with varied numbers of users, items, and reviews of up to 44187, 26386, and 426791, respectively. The performance has been benchmarked against thirteen baseline algorithms and the experimental results demonstrate a significant improvements of up to 24.72%, 64.28%, 48.79%, and 61% in RMSE, and 55.9%, 76.7%, 67.6%, and 71.5% in MAE for a 90:10 train-test split with Digital Music, Fashion, Magazine Subscriptions and Video Games datasets from Amazon, respectively. Similar results have been observed for the 80:20 train-test split.

The interplay between LHCSR and PSBS proteins provides photoprotection in Chlamydomonas reinhardtii pgr5 mutant under high light

Cyclic electron transport (CET) is a vital alternative route that protects against photodamage and aids in energy production. This process depends on proton gradient regulation 5 (PGR5) and PGRL1-dependent pathways associated with CET. The exact roles of these proteins in photosystem I photochemistry under prolonged high light conditions are not fully understood. Continuous light adaptation hinges on two critical mechanisms: alterations in the proton motive force (pmf) and adjustments in the ratio of proteins activated by high light that dissipate excess light through non-photochemical quenching (NPQ). To explore this, we studied pgrl1 and pgr5 mutants to gauge their roles in balancing photochemistry and photoacclimation. These mutants showed inhibited growth, reduced photosynthetic efficiency, and a lowered pmf, leading to diminished non-photochemical energy quenching (qE) under high light. Prolonged high light exposure slowed down unregulated energy losses Y(NO), and relaxation helped regulate photosynthetic activity by increasing photoinhibitory quenching (qI), thus preventing further damage to the photosystem. The precise balance between the two pmf components, ΔpH and Δψ, is critical for controlling photochemistry and photoacclimation, yet remains elusive. In pgr5 reduced pmf led to an accumulation of cytochrome b6f under high light, and a decrease in the ΔpH component increased the Δψ component's role in photosynthetic acclimation. Notably, light-harvesting complex stress response protein 3 (LHCSR3) showed decreased expression in pgrl1, whereas pgr5 exhibited no expression of both LHCSR3 and LHCSR1 under high light conditions. Moreover, continuous increase in PSBS protein accumulation in pgr5 suggests enhanced photoprotection in the absence of LHCSR3 under high light. The study provides significant insights into how cyclic electron transport (CET) regulates photoprotective proteins LHCSR and PSBS, influencing Chlamydomonas' survival strategies.

Facilitating the electrooxidation of 5-hydroxymethylfurfural on nickel hydroxide through deintercalation

The electrocatalytic of 5-hydroxymethylfurfural oxidation reaction (HMFOR) is an alternative route for the green production of valuable oxygenated chemicals. Nickel hydroxides, which consist of hydroxide layers and interlayer charge-balancing anions, are a type of promising catalysts for HMFOR. Progresses have been made on elucidating the correlation between the hydroxide layer and HMFOR performance, while the effect of intercalated anions on the activity remains unclear. Herein, two self-supported nickel hydroxide catalysts (i.e., pristine Ni(OH)2/CP-F and deintercalated Ni(OH)2/CP-A) are employed for revealing the relationship between anion-deintercalation and HMFOR activity. Physical characterizations demonstrate that the deintercalation phenomenon can alter the d-band center and increase the electron density of the Ni site. This endows the deintercalated Ni(OH)2/CP-A with improved electrochemical properties (conversion = 99.99 %; FDCA yield > 99 %; FE > 99 %), enhanced adsorption strength for HMF, and increased intrinsic activity, compared to the pristine Ni(OH)2/CP-F. This work not only reports an excellent HMFOR electrocatalyst, but also manifests the crucial effect of deintercalation on the electrochemical oxidation performance of Ni(OH)2.

Perceptions of undertaking a higher degree alongside dental specialty training: A cross-sectional survey of UK dental specialty trainees.

The curricula for UK dental specialty training have recently been under review and until 2024, completion of a research component during training in Dental Public Health, Oral Microbiology and Orthodontics has been mandatory (with an alternative route for Orthodontics involving the submission of two scientific papers for those trainees not wishing to undertake a higher degree). Anecdotally, some trainees in other dental specialties choose to undertake higher degrees alongside specialty training. The aims were to investigate how many dental specialty registrars study for higher degrees alongside specialty training, and whether undertaking a higher degree alongside specialty training has an impact on completion of training, research skills, research experience, patient care and career opportunities. This was a cross-sectional study design, involving the distribution of an online, anonymous questionnaire-based survey to UK dental specialty registrars in November and December 2022. In total, 38 questionnaires were completed, representing a 7.7% response rate of the entire dental specialty registrar cohort in the UK and 42% of those who received it. Most respondents (76.3%) were either studying or had completed a clinically relevant higher degree prior to specialty training. Most respondents (76.3%) reported that the higher degree increased career opportunities and gave them additional skills. Dental specialty trainees who responded to this survey perceived the higher degree to be beneficial in terms of preparing for exams, gaining skills in critical appraisal and for increasing future career opportunities.

Formulation and Optimization of Solid Lipid Nanoparticle-based Gel for Dermal Delivery of Linezolid Using Taguchi Design.

Linezolid (LNZ) is a synthetic oxazolidinone antibiotic approved for the treatment of uncomplicated and complicated skin and soft tissue infections caused by gram-positive bacteria. Typically, LNZ is administered orally or intravenously in most cases. However, prolonged therapy is associated with various side effects and life threatening complications. Cutaneous application of LNZ will assist in reducing the dose, hence minimizing the unwanted side/adverse effects associated with oral administration. Dermal delivery provides an alternative route of administration, facilitating a local and sustained concentration of the antimicrobial at the site of infection. The current research work aimed to formulate solid lipid nanoparticles (SLNs) based gel for dermal delivery of LNZ in the management of uncomplicated skin and soft tissue infections to maximise its benefits and minimise the side effects. SLNs were prepared by high-shear homogenisation and ultrasound method using Dynasan 114 as solid lipid and Pluronic F-68 as surfactant. The effect of surfactant concentration, drug-to-lipid ratio, and sonication time was investigated on particle size, zeta potential, and entrapment efficiency using the Taguchi design. The main effect plot of means and signal-to-noise ratio were generated to determine the optimized formulation. The optimized batch was formulated into a gel, and ex-vivo permeation study, in-vitro and in-vivo antibacterial activity were conducted. The optimised process parameters to achieve results were 2% surfactant concentration, a drug-to-lipid ratio of 1:2, and 360 s of sonication time. The optimized batch was 206.3± 0.17nm in size with a surface charge of -24.4± 4.67mV and entrapment efficiency of 80.90 ± 0.45%. SLN-based gel demonstrated anomalous transport with an 85.43% in vitro drug release. The gel showed a 5 cm zone of inhibition while evaluated for in vitro antibacterial activity against Staphylococcus aureus. Ex-vivo skin permeation studies demonstrated 20.308% drug permeation and 54.96% cutaneous deposition. In-vivo results showed a significant reduction in colony-forming units in the group treated with LNZ SLN-based gel. Ex-vivo studies ascertain the presence of the drug at the desired site and improve therapy. In-vivo results demonstrated the ability of SLN-based gel to significantly reduce the number of bacteria in the stripped infection model. The utilization of SLN as an LNZ carrier holds significant promise in dermal delivery.

Thermoradiative Photovoltaics

Devices that operate like solar cells in reverse can generate power even in the absence of sunlight, offering an alternative route for energy production.