Analysing Amino Acids in Galanin Graph Theoretical Approach

Graph theoretical analysis is an important area of the research in biological networks. Here first we introduce Pt-graph of peptide/protein based on physicochemical properties and adjacency of amino acids in the corresponding peptide/protein. Based on the Pt-graph, we introduce the graph of species which containing the peptide/protein named as SPt-graph. Finally, we analyze graph theoretically Pt-graphs of fourteen species of animals containing Galanin, a neuropeptide and their SPt-graph. From the graph theoretical analyses of Pt-graph and SPt-graph we get some observations about the relations among the amino acids, physicochemical properties of amino acids, peptide/protein and species containing peptide/protein and it may help in the field of evolution of peptide/protein and drug design in future

Progressive Damage and Failure Analysis of Bonded Composite Joints at High Energy Dynamic Impacts

Both wing and fuselage structures utilize bonded composite joints for structural efficiency in modern commercial and military aircraft. To ensure compliance with certification requirements mechanical fasteners are typically used as a failsafe mechanism for appropriate strength in the event of complete stiffener disbond. However, the use of fasteners decreases the structural efficiency of the structure by adding weight. This establishes the requirement to better exploit the efficiency of bonded structures and fully understand the failure behavior of adhesively bonded composite structures, particularly when subjected to elevated loading rates due to high energy dynamic impacts (HEDI). For this reason, the NASA Advanced Composite Consortium (ACC) HEDI team developed an experimentation and numerical modeling program for high rate loading of composite joints. In the present work, the response of adhesively bonded composite joints subjected to elevated loading rates is studied numerically and validated against experimental results. Due to dynamic considerations of experiments, the idea of wedge insert was extended to use with Split Hopkinson Pressure Bar (SHPB) testing techniques. Mode-I and Mode-II test configurations were simulated to evaluate the capability of two continuum damage material (CDM) models in LS-DYNA, namely MAT162 and MAT261. Three different levels of fidelity were considered to investigate the level of detail required to numerically predict the failure behavior and the results from high fidelity analysis are presented

DEVELOPMENT AND IN VITRO EVALUATION OF NANOLIPID CARRIERS OF CLOBETASOL PROPIONATE AND PRAMOXINE HYDROCHLORIDE FOR TOPICAL DELIVERY

Objective: Formulation and characterization of clobetasol propionate (CP) and pramoxine hydrochloride (PH) loaded nanostructured lipid carriers (NLC) offering improved performance in terms of drug loading and long-term stability for topical drug delivery. Methods: Drug-loaded NLC formulation was designed by melt-emulsification ultrasonication technique, by fluctuating the concentration of stearic acid and oleic acid. Poloxamer F68 and tween 80 were used as surfactants in the formulation and soya lecithin was used as stabilizer and co-surfactant. Differential scanning calorimetry (DLS), scanning electron microscopic studies (SEM), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), x-ray diffraction (XRD), are the techniques used to characterize the preparations. Optimized drug-loaded formulations were evaluated for particle size, zeta potential, entrapment efficiency, in vitro drug release, hemocompatibility assay and cytotoxicity screening. Results: For drug loaded formulation the particle size was found in nanometric range. In vitro drug release was carried out using dialysis membrane and drug release after 24h was found to be 90.98 %±1.89 for CP and 79.81 %±4.20 for PH. Conclusion: The formulated NLC is a potential approach for sustained release of drug which may reduce systemic side effects, increase skin retention time and duration of action. Further in vivo studies will confirm the effect of NLC to increase skin retention time, decreases systemic absorption of the corticosteroid thereby avoiding side effects

Enhanced Lymphatic Uptake of Leflunomide Loaded Nanolipid Carrier via Chylomicron Formation for the Treatment of Rheumatoid Arthritis

Purpose: The current study aims the lymphatic delivery of leflunomide loaded nanostructured lipid carriers (LNLC) for the treatment of rheumatoid arthritis, mainly focussed to enhance the lymphatic delivery via chylomicron formation, improved bioavailability and reduced systemic toxicity. Methods: Melt emulsification ultra-sonication method was used to formulate the nanostructured lipid carrier (NLC) containing leflunomide. Four batches were prepared by using various concentration of surfactants (tween 80 and poloxmer 188) and lipid mixtures (stearic acid and oleic acid). All the formulations were studied for various physiochemical properties Results: The formulation with increased concentration of lipid and surfactants showed highest entrapment efficiency (93.96 ± 0.47%) and better drug release (90.35%) at the end of 48 hrs. In vivo tests were carried out to determine the antiarthritic potential of the formulation in Sprague-dawley rats for a duration of 30d. The effect was evaluated by measuring the reduction in knee thickness. LNLC showed a marked reduction in inflammation compared to standard drug. Intestinal lymphatic uptake studies of LNLC were performed by intraduodenal administration and compared with leflunomide drug solution. The mesenteric lymph node was analysed by HPLC method and the concentration of drug was estimated. It showed that LNLC having highest uptake (40.34μg/ml) when compared with leflunomide drug solution (10.04μg/ml). Radiographic analysis and histopathological studies showed the formation of healthy cartilage after treatment period. Conclusion: The results suggested that LNLC has the potential to reduce the systemic toxicities associated with conventional therapy along with improved efficacy in the treatment of rheumatoid arthritis

Nitrogen as an environmentally friendly suppression agent for aircraft cargo fire safety

Fire suppression systems in cargo compartments are a certification requirement for commercial aircraft safety. Halon production was banned and usage ends in 2040 according to Montreal Protocol for environmental reasons. This necessitates an alternative environmentally friendly agent. Quantitative analysis of nitrogen as agent established suitability of the suppression system. The Minimum Performance Standards specifies the qualification procedure of an agent through four scenarios – bulk load; containerised load; surface burning; and aerosol can explosion. Empirical sources from Airbus, independent computational fluid dynamics studies and small-scale cup-burner tests indicate suitability of nitrogen specific to aircraft cargo fire suppression. The nitrogen delivery system and the experimental apparatus are presented. Extensive commissioning tests verified instrumentation reliability. All the four scenarios were conducted at Cranfield University, in a replica of a wide-body aircraft cargo compartment. In a reduced oxygen environment (11%) obtained with nitrogen discharge, the aerosol can explosion tests were performed without any evidence of explosion or pressure increase beyond the expected baseline value. The surface burning scenario was completed successfully and passed the Minimum Performance Standard criteria. The maximum average temperature was found to be 220°C (limit – 293°C). All the scenarios passed the Minimum Performance Standard criteria for indicating successful prevention of Class B fire re-ignition. Similarly, the containerised and bulk-load scenarios obtained results that passed the Minimum Performance Standard criteria for successfully maintaining continued fire suppression for a specified period of time. The maximum average temperature in containerised-load fire scenario was found to be 210°C (limit – 343°C) and in bulk-load scenario was 255°C (limit – 377°C). Additional qualification criteria and system design are presented in this article according to the Minimum Performance Standard format. This work can be extended to introduce standard testing for safety critical systems, such as engine bay and lithium-ion fires

Numerical assessment for aircraft cargo compartment fire suppression system safety

Fire on board an aircraft cargo compartment can lead to catastrophic consequences. Therefore, fire safety is one of the most important considerations during aircraft design and certification. Conventionally, Halon-based agents were used for fire suppression in such cases. However, an international agreement under the Montreal Protocol of 1994 banned further production of Halon and several other halocarbons considered harmful to the environment. There is therefore a requirement for new suppression agents, along with suitable system design and certification. This article aims to describe the creation of a mechanism to validate a preliminary design for fire suppression systems using Computational Fluid Dynamics and provide further guidance for fire suppression experiments in aircraft cargo compartments. Investigations were performed for the surface burning fire, one of the fire testing scenarios specified in the Minimum Performance Standard, using the numerical code Fire Dynamics Simulator. This study investigated the use and performance of nitrogen, a potential replacement for Halon 1301, as an environmentally friendly agent for cargo fire suppression. Benchmark fires using the pyrolysis model and fire design model were built for the surface-burning fire scenario. Compared with experiment results, the two Computational Fluid Dynamics models captured the suppression process with high accuracy and displayed similar temperature and gas concentration profiles. Fire consequences in response to system uncertainties were studied using fire curves with various fire growth rates. The results suggested that using nitrogen as a fire suppression agent could achieve a lower post-suppression temperature compared to a Halon 1301-based system. It can therefore be considered as a potential candidate for aircraft cargo fire suppression. Such work will feed directly into system safety assessments during the early design stages, where analyses must precede testing. Future work proposed for the application of this model can be extended to other fire scenarios such as buildings, shipping, and surface transport vehicles

Performance evaluation of nitrogen for fire safety application in aircraft

Fire suppression is an important safety certification requirement for aircraft as it is for all safety critical systems. Risk analyses are required at the design and certification stages to determine the probabilities and means of mitigating such risks. [18] shows an approach for spacecraft, [19] for passenger ships and [30] for reactors. An important analysis tool for aircraft is the Zonal Analysis process [31]. Such analyses include investigation of means of fire suppression for which the use of Halon 1301 was a popular choice. The production of Halon and several halocarbons were banned under the Montreal Protocol in 1994, which necessitates an investigation for use of environmental-friendly agents for this application. The primary objective of this paper is to determine the ‘design concentration’1 of nitrogen required for fire suppression. Computational Fluid Dynamics (CFD), in combination with experimental verification is described in this paper. The air flow rate in the cup-burner model was varied between 10 L/min and 40 L/min for a low-speed numerical model and was validated against the BS ISO 14520 cup burner test [1] to determine the extinguishing concentration of nitrogen. The study revealed that the design concentration of nitrogen was 34% (14% oxygen concentration). Further investigation suggested that at low air flow rates (10L/min and 20 L/min case), distortions produced in the flow led to erroneous measurement of oxygen concentration in experiments. The fire suppression model was extended to an n-heptane pool fire in a large enclosure. The recorded design concentration was approximately 39% additional nitrogen corresponding to 13% oxygen concentration by volume. It was observed that the weight of nitrogen required increased by 7.5 times compared to Halon 1301 use for this model. Future work can be explored in aircraft cargo and engine bay fire safety systems through Minimum Performance Standard (MPS) testing and simulations with nitrogen as the agent. Such work will feed directly into system safety assessments during the early design stages, where analyses must precede testing

A COMPARATIVE STUDY OF ID3 AND MLP ALGORITHMS

Data mining on large databases has been a major concern in research community. To overcome the difficulty of analyzing huge amounts of data, classification is done on the datasets. In our project, we have used two classification algorithms ID3 and MLP. We focused on applying the concept of ID3 algorithm to find the nodes in the decision tree and back-propagation to calculate the weights of artificial neural network. These concepts are used for training the decision tree and artificial neural network classifiers for PIMA dataset. The classifiers thus obtained from training phase are tested. Then the corresponding accuracies are calculated and compared to find the efficient algorithm among ID3 and MLP

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly