Search results for: net zero targets

Authors: Pornpimol Chaiwuttisak, Honora Smith, Yue Wu

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Blood is a perishable product which suffers from physical deterioration with specific fixed shelf life. Although its value during the shelf life is constant, fresh blood is preferred for treatment. However, transportation costs are a major factor to be considered by administrators of Regional Blood Centres (RBCs) which act as blood collection and distribution centres. A trade-off must therefore be reached between transportation costs and short-term holding costs. In this paper we propose a number of algorithms for online allocation and routing of blood supplies, for use in conditions of variable and insufficient blood supply. A case study in northern Thailand provides an application of the allocation and routing policies tested. The plan proposed for daily allocation and distribution of blood supplies consists of two components: firstly, fixed routes are determined for the supply of hospitals which are far from an RBC. Over the planning period of one week, each hospital on the fixed routes is visited once. A robust allocation of blood is made to hospitals on the fixed routes that can be guaranteed on a suitably high percentage of days, despite variable supplies. Secondly, a variable daily route is employed for close-by hospitals, for which more than one visit per week may be needed to fulfil targets. The variable routing takes into account the amount of blood available for each day’s deliveries, which is only known on the morning of delivery. For hospitals on the variables routes, the day and amounts of deliveries cannot be guaranteed but are designed to attain targets over the six-day planning horizon. In the conditions of blood shortage encountered in Thailand, and commonly in other developing countries, it is often the case that hospitals request more blood than is needed, in the knowledge that only a proportion of all requests will be met. Our proposal is for blood supplies to be allocated and distributed to each hospital according to equitable targets based on historical demand data, calculated with regard to expected daily blood supplies. We suggest several policies that could be chosen by the decision makes for the daily distribution of blood. The different policies provide different trade-offs between transportation and holding costs. Variations in the costs of transportation, such as the price of petrol, could make different policies the most beneficial at different times. We present an application of the policies applied to a realistic case study in the RBC at Chiang Mai province which is located in Northern region of Thailand. The analysis includes a total of more than 110 hospitals, with 29 hospitals considered in the variable route. The study is expected to be a pilot for other regions of Thailand. Computational experiments are presented. Concluding remarks include the benefits gained by the online methods and future recommendations.

Keywords: online algorithm, blood distribution, developing country, insufficient blood supply

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Authors: Anupama Sahoo, Bongyong Lee, Katia Boniface, Julien Seneschal, Sanjaya K. Sahoo, Tatsuya Seki, Chunyan Wang, Soumen Das, Xianlin Han, Michael Steppie, Sudipta Seal, Alain Taieb, Ranjan J. Perera

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Vitiligo is a common, chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has a complex immune, genetic, environmental, and biochemical etiology, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. Here we characterized the human vitiligo cell line PIG3V and the normal human melanocytes, HEM-l by RNA-sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched miR-211, a known metabolic switch in non-pigmented melanoma cells, was severely downregulated in vitiligo cell line PIG3V and skin biopsies from vitiligo patients, while its novel predicted targets transcriptional co-activator PGC1-α (PPARGC1A), ribonucleotide reductase regulatory subunit M2 (RRM2), and serine-threonine protein kinase TAO1 (TAOK1) were reciprocally upregulated. miR-211 binds to PGC1-α 3’UTR locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated miR-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of miR-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo.

Keywords: metabolism, microRNA, mitochondria, vitiligo

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Authors: Jonathan K. Hill

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The transportation networks throughout Africa remain the only transportation infrastructure system in the world that is attacked by terrorists at a high frequency, so the international community can learn from each attack. The targeting of transportation should be recognized as a direct attack against a civilian population, so the international community should work to better understand the types of attacks utilized, the types of improvised explosive device designs adapted to transportation targets, and the ways the various modes of transportation have been attacked throughout the continent. Some countries have seen grenade attacks that have resulted in only injuries, while some countries have experienced large vehicle bombings that have resulted in hundreds of injuries and numerous deaths. With insurgencies, explosive devices have been small, complex, and generally target an enemy of the insurgency. With terrorist bombings, the explosive devices have been large, brazen, and targeted at civilian populations. And, these civilian populations are easily targeted within the transportation system. The presentation provided by Assess Africa LLC is titled ‘Evolution of Bombings Against Transportation Infrastructure’ and covers improvised explosive device characteristics, how improvised explosive devices have been adapted to transportation targets in Africa, analyses recent incidents, and provides some advice for effective protective measures. A main component of the improvised explosive device characteristics portion of the presentation focuses on the link between explosive device components, the intelligence network, and the bomb-builder’s network. By understanding the components, how the use of various components can be linked to a terrorist group’s capabilities, and how the bomb-builder acquires materials, the analysis of improvised explosive device attacks takes on a new direction – one that focuses on defeating the network instead of merely reviewing incidents of the past.

Keywords: Africa, bombings, critical infrastructure protection, transportation security

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Authors: H. Duggal, G. Singh, G. Singh, A. Bhalla, S. Kumar, J. S. Shahi, D. Mehta

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The total differential cross section for scattering of the 5.895 keV photons by various polymers has been measured at scattering angle of 135o. The experimental measurements were carried out using the energy dispersive setup involving annular source of the 55Fe radioisotope and a low energy germanium (LEGe) detector. The cross section values are measured for 20 polymer targets namely, Paraffin Wax, Polytetrafluoro ethylene (PTFE), Cellulose, Silicone oil, Polyvinyl alcohol (PVA), Polyvinyl purrolidone (PVP), Polymethyl methacrylate (PMMA), Kapton, Mylar, Chitosan, Polyvinyl chloride (PVC), Bakelite, Carbopol, Chlorobutyl rubber (CBR), Polyetylene glycol (PEG), Polysorbate-20, Nylon-6, Cetyl alcohol, Carboxyl methyl sodium cellulose and Sodium starch glucolate. The measurements were performed in vacuum so as to avoid scattering contribution due to air and strong absorption of low energy photons in the air column. In the present investigations, the geometrical factor and efficiency of the detector were determined by measuring the K x-rays emitted from the 22Ti and 23V targets excited by the Mn K x-rays in the same experimental set up. The measured scattering cross sections have been compared with the sum of theoretically calculated elastic and inelastic scattering cross sections. The theoretical elastic (Rayleigh) scattering cross sections based on the various form factor approximations, namely, non-relativistic form factor (NF), relativistic form factor (RF), modified form factor (MF), and MF with anomalous scattering factor (ASF) as well as the second order S-matrix formalisms, and the inelastic scattering differential cross sections based on the Klein-Nishina formula after including the inelastic scattering function (KN+ISF) have been calculated. The experimental results show fairly good agreement with theoretical cross sections.

Keywords: photon, polymers, elastic and inelastic, scattering cross sections

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Authors: Zue-Chin Chang

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RF magnetron sputtering is used on the ceramic targets, each of which contains zinc oxide (ZnO), zinc oxide doped with aluminum (AZO) and zinc oxide doped with gallium (GZO). The XRD analysis showed a preferred orientation along the (002) plane for ZnO, AZO, and GZO films. The AZO film had the best electrical properties; it had the lowest resistivity of 6.6 × 10-4 cm, the best sheet resistance of 2.2 × 10-1 Ω/square, and the highest carrier concentration of 4.3 × 1020 cm-3, as compared to the ZnO and GZO films.

Keywords: aging, films, microstructure, photoelectric property

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Authors: Shunsuke Aoki, Taku Ri, Tatsuya Yamazaki

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These days, along with the development of e-sports, video games as a competitive sport is attracting attention. But, in many cases, action in the screen does not match the real motion of operation. Inclusiveness of player motion is needed to increase reality and excitement for sports games. Therefore, in this study, the authors propose a method to recognize player motion by using the motion capture technology and develop a virtual basketball game. The virtual basketball game consists of a screen with nine targets, players, depth sensors, and no ball. The players pretend a two-handed basketball shot without a ball aiming at one of the nine targets on the screen. Time-series data of three-dimensional coordinates of player joints are captured by the depth sensor. 20 joints data are measured for each player to estimate the shooting motion in real-time. The trajectory of the thrown virtual ball is calculated based on the time-series data and hitting on the target is judged as success or failure. The virtual basketball game can be played by 2 to 4 players as a competitive game among the players. The developed game was exhibited to the public for evaluation on the authors' university open campus days. 339 visitors participated in the exhibition and enjoyed the virtual basketball game over the two days. A questionnaire survey on the developed game was conducted for the visitors who experienced the game. As a result of the survey, about 97.3% of the players found the game interesting regardless of whether they had experienced actual basketball before or not. In addition, it is found that women are easy to comfort for shooting motion. The virtual game with motion capture technology has the potential to become a universal entertainment between e-sports and actual sports.

Keywords: basketball, motion capture, questionnaire survey, video ga

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Authors: Mustafa Engin Başoğlu, Bekir Çakir

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Since large part of electricity generation is provided by using fossil based resources, energy is an important agenda for countries. Depletion of fossil resources, increasing awareness of climate change and global warming concerns are the major reasons for turning to alternative energy resources. Solar, wind and hydropower energy are the main renewable energy sources. Among of them, wind energy is promising for Turkey whose installed power capacity increases approximately eight times between 2008 - seventh month of 2014. Signing of Kyoto Protocol can be accepted as a milestone for Turkey's energy policy. Turkish government has announced 2023 Vision (2023 targets) in 2010-2014 Strategic Plan prepared by Ministry of Energy and Natural Resources (MENR). 2023 Energy targets can be summarized as follows: Share of renewable energy sources in electricity generation is 30% of total electricity generation by 2023. Installed capacity of wind energy will be 20 GW by 2023. Other renewable energy sources such as solar, hydropower and geothermal are encouraged with new incentive mechanisms. Share of nuclear power plants in electricity generation will be 10% of total electricity generation by 2023. Dependence on foreign energy is reduced for sustainability and energy security. As of seventh month of 2014, total installed capacity of wind power plants is 3.42 GW and a lot of wind power plants are under construction with capacity 1.16 GW. Turkish government also encourages the locally manufactured equipments. MILRES is an important project aimed to promote the use of renewable sources in electricity generation. A 500 kW wind turbine will be produced in the first phase of project. Then 2.5 MW wind turbine will be manufactured domestically within this project

Keywords: wind energy, wind speed, 2023 vision, MILRES, wind energy potential in TURKEY

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Authors: Hongquan Zhang

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Inspired by endogenous protein motors, researchers have constructed various synthetic DNA motors based on the specificity and predictability of Watson-Crick base pairing. However, the application of DNA motors to signal amplification and biosensing is limited because of low mobility and difficulty in real-time monitoring of the walking process. The objective of our work was to construct a new type of DNA motor termed target-triggered DNA motors that can walk for hundreds of steps in response to a single target binding event. To improve the mobility and processivity of DNA motors, we used gold nanoparticles (AuNPs) as scaffolds to build high-density, three-dimensional tracks. Hundreds of track strands are conjugated to a single AuNP. To enable DNA motors to respond to specific protein and nucleic acid targets, we adapted the binding-induced DNA assembly into the design of the target-triggered DNA motors. In response to the binding of specific target molecules, DNA motors are activated to autonomously walk along AuNP, which is powered by a nicking endonuclease or DNAzyme-catalyzed cleavage of track strands. Each moving step restores the fluorescence of a dye molecule, enabling monitoring of the operation of DNA motors in real time. The motors can translate a single binding event into the generation of hundreds of oligonucleotides from a single nanoparticle. The motors have been applied to amplify the detection of proteins and nucleic acids in test tubes and live cells. The motors were able to detect low pM concentrations of specific protein and nucleic acid targets in homogeneous solutions without the need for separation. Target-triggered DNA motors are significant for broadening applications of DNA motors to molecular sensing, cell imagining, molecular interaction monitoring, and controlled delivery and release of therapeutics.

Keywords: biosensing, DNA motors, gold nanoparticles, signal amplification

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Authors: Debatosh Das, Moxian Chen, Jianhua Zhang, Caroline Gutjahr

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Arbuscular mycorrhiza (AM) is a mutualistic symbiosis between plant roots and Glomeromycotina fungi, which is activated under low but inhibited by high phosphate. The effect of phosphate on AM development has been observed for many years, but mechanisms regulating it under contrasting phosphate levels remain unknown. Based on previous observations that promoters of several AM functional genes contain PHR binding motifs, we hypothesized that PHR2, a master regulator of phosphate starvation response in rice, was recruited to regulate AM symbiosis development. We observed a drastic reduction in root colonization and significant AM transcriptome modulation in phr2. PHR2 targets genes required for root colonization and AM signaling. The role of PHR2 in improving root colonization, mycorrhizal phosphate uptake, and growth response was confirmed in field soil. In conclusion, rice PHR2, which is considered a master regulator of phosphate starvation responses, acts as a positive regulator of AM symbiosis between Glomeromycotina fungi and rice roots. PHR2 directly targets the transcription of plant strigolactone and AM genes involved in the establishment of this symbiosis. Our work facilitates an understanding of ways to enhance AMF propagule populations introduced in field soils (as a biofertilizer) in order to restore the natural plant-AMF networks disrupted by modern agricultural practices. We show that PHR2 is required for AM-mediated improvement of rice yield in low phosphate paddy field soil. Thus, our work contributes knowledge for rational application of AM in sustainable agriculture. Our data provide important insights into the regulation of AM by the plant phosphate status, which has a broad significance in agriculture and terrestrial ecosystems.

Keywords: biofertilizer, phosphate, mycorrhiza, rice, sustainable, symbiosis

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Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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Authors: Rinat Arbel-Goren, Joel Stavans

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Cell-to-cell variations in transcript or protein abundance, called noise, may give rise to phenotypic variability between isogenic cells, enhancing the probability of survival under stress conditions. These variations may be introduced by post-transcriptional regulatory processes such as non-coding, small RNAs stoichiometric degradation of target transcripts in bacteria. We study the iron homeostasis network in Escherichia coli, in which the RyhB small RNA regulates the expression of various targets as a model system. Using fluorescence reporter genes to detect protein levels and single-molecule fluorescence in situ hybridization to monitor transcripts levels in individual cells, allows us to compare noise at both transcript and protein levels. The experimental results and computer simulations show that extrinsic noise buffers through a feed-forward loop configuration the increase in variability introduced at the transcript level by iron deprivation, illuminating the important role that extrinsic noise plays during stress. Surprisingly, extrinsic noise also decouples of fluctuations of two different targets, in spite of RyhB being a common upstream factor degrading both. Thus, phenotypic variability increases under stress conditions by the decoupling of target fluctuations in the same cell rather than by increasing the noise of each. We also present preliminary results on the adaptation of cells to prolonged iron deprivation in order to shed light on the evolutionary role of post-transcriptional downregulation by small RNAs.

Keywords: cell-to-cell variability, Escherichia coli, noise, single-molecule fluorescence in situ hybridization (smFISH), transcript

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Authors: Anukriti Verma, Bhawna Rathi, Shivani Sharda

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Reactive Arthritis (ReA) is a disorder that causes inflammation in joints due to certain infections at distant sites in the body. ReA begins with stiffness, pain, and inflammation in these areas especially the ankles, knees, and hips. It gradually causes several complications such as conjunctivitis in the eyes, skin lesions in hand, feet and nails and ulcers in the mouth. Nowadays the diagnosis of ReA is based upon a differential diagnosis pattern. The parameters for differentiating ReA from other similar disorders include physical examination, history of the patient and a high index of suspicion. There are no standard lab tests or markers available for ReA hence the early diagnosis of ReA becomes difficult and the chronicity of disease increases with time. It is reported that enteric disorders such as Inflammatory Bowel Disease (IBD) that is inflammation in gastrointestinal tract namely Crohn’s Disease (CD) and Ulcerative Colitis (UC) are reported to be linked with ReA. Several microorganisms are found such as Campylobacter, Salmonella, Shigella and Yersinia causing IBD leading to ReA. The aim of our study was to perform the in-silico analysis in order to find interactions between microorganisms and human host causing IBD leading to ReA. A systems biology approach for metabolic network reconstruction and simulation was used to find the essential genes of the reported microorganisms. Interactomics study was used to find the interactions between the pathogen genes and human host. Genes such as nhaA (pathogen), dpyD (human), nagK (human) and kynU (human) were obtained that were analysed further using the functional, pathway and network analysis. These genes can be used as putative drug targets and biomarkers in future for early diagnosis, prevention, and treatment of IBD leading to ReA.

Keywords: drug targets, inflammatory bowel disease, reactive arthritis, systems biology

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Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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Authors: Devinder Kaur Sugga, Ekamdeep Kaur, Jaspreet Kaur, C. Rajesh, Preeti Rajesh, Harsimran Kaur

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Withanolides are steroidal lactones and are highly oxygenated phytoconstituents that can be developed as potential anti-carcinogenic agents. The two main withanolides, namely Withaferin A and Withanolides D, have been extensively studied for their pharmacological activities. Both these withanolides are present in the Withania somnifera (WS) leaves belonging to the family Solanaceae, also known as “Indian ginseng .”In this study effects of WS leaf extract on the MCF7 breast cancer cell line were investigated by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects and in vitro wound-healing assay to study the effect on cancer cell migration. Our data suggest WS extracts have cytotoxic effects and are effective anti-migrating agents and thus can be a source of potential candidates for the development of potential agents against metastasis. Thus, it can be a source of potential candidates for the development of potential agents against metastasis. Insight into these results, the in-silico approach to identify the possible protein targets interacting with withanolides was taken. Protein kinase C alpha (PKCα) was among the selected 5 top-ranked target proteins identified by the Swiss Target Prediction tool. PKCα is known to promote the growth and invasion of cancer cells and is being evaluated as a prognostic biomarker and therapeutic target in clinically aggressive tumors. Molecular docking of Withaferin A and Withanolides D was performed using AutoDock Vina. Both the bioactive compounds interacted with PKCα. The targets predicted using this approach will serve as leads for the possible therapeutic potential of withanolides, the bioactive ingredients of WS extracts, as anti-cancer drugs.

Keywords: withania somnifera, withaferin A, withanolides D, PKCα

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Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav

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Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.

Keywords: aquaporin, gene expression, lung injury, toxicant exposure

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Authors: Saeeda Batool, Ather Maqsood Ahmed

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This study investigates the impact of public healthcare facilities and socio-economic circumstances on the status of child health in Pakistan. The complete analysis is carried out in correspondence with fourth and sixth millennium development goals. Further, the health variables chosen are also inherited from targeted indicators of the mentioned goals (MDGs). Trends in the Human Opportunity Index (HOI) for both health inequalities and coverage are analyzed using the Pakistan Social and Living Standards Measurement (PLSM) data set for 2001-02 to 2012-13 at the national and provincial level. To reveal the relative importance of each circumstance in achieving the targeted values for child health, Shorrocks decomposition is applied on HOI. The annual point average growth rate of HOI is used to simulate the time period for the achievement of target set by MDGs and universal access also. The results indicate an improvement in HOI for a reduction in child mortality rates from 52.1% in 2001-02 to 67.3% in 2012-13, which confirms the availability of healthcare opportunities to a larger segment of society. Similarly, immunization against measles and other diseases such as Diphtheria, Polio, Bacillus Calmette-Guerin (BCG), and Hepatitis has also registered an improvement from 51.6% to 69.9% during the period of study at the national level. On a positive note, no gender disparity has been found for child health indicators and that health outcome is mostly affected by the parental and geographical features and availability of health infrastructure. However, the study finds that this achievement has been uneven across provinces. Pakistan is not only lagging behind in achieving its health goals, disappointingly with the current rate of health care provision, but it will take many additional years to achieve its targets.

Keywords: socio-economic circumstances, unmet MDGs, public healthcare services, child and infant mortality

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Authors: Jari Koskiaho, Teija Kirkkala, Jani Salminen, Sarianne Tikkanen, Sirkka Tattari

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Here, phosphorus (P) loading to the lake Pyhäjärvi (SW Finland) was reviewed, load reduction targets were determined, and different measures of waterwise circular economy to reach the targets were evaluated. In addition to the P loading from the lake’s catchment, there is a significant amount of internal P loading occurring in the lake. There are no point source emissions into the lake. Thus, the most important source of external nutrient loading is agriculture. According to the simulations made with LLR-model, the chemical state of the lake is at the border of the classes ‘Satisfactory’ and ‘Good’. The LLR simulations suggest that a reduction of some hundreds of kilograms in annual P loading would be needed to reach an unquestionably ‘Good’ state. Evaluation of the measures of the waterwise circular economy suggested that they possess great potential in reaching the target P load reduction. If they were applied extensively and in a versatile, targeted manner in the catchment, their combined effect would reach the target reduction. In terms of cost-effectiveness, the waterwise measures were ranked as follows: The best: Fishing, 2nd best: Recycling of vegetation of reed beds, wetlands and buffer zones, 3rd best: Recycling field drainage waters stored in wetlands and ponds for irrigation, 4th best: Controlled drainage and irrigation, and 5th best: Recycling of the sediments of wetlands and ponds for soil enrichment. We also identified various waterwise nutrient recycling measures to decrease the P content of arable land. The cost-effectiveness of such measures may be very good. Solutions are needed to Finnish water protection in general, and particularly for regions like lake Pyhäjärvi catchment with intensive domestic animal production, of which the ‘P-hotspots’ are a crucial issue.

Keywords: circular economy, lake protection, mitigation measures, phosphorus

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Authors: Yifan Hou, Haibo Liu, Le Jiang, Wandong Su, Binqing Wang

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Road defect detection is crucial for modern urban management and infrastructure maintenance. Traditional road defect detection methods mostly rely on manual labor, which is not only inefficient but also difficult to ensure their reliability. However, existing deep learning-based road defect detection models have poor detection performance in complex environments and lack robustness to multi-scale targets. To address this challenge, this paper proposes a distinct detection framework based on the one stage algorithm network structure. This article designs a deep feature extraction network based on RCSDarknet, which applies channel shuffling to enhance information fusion between tensors. Through repeated stacking of RCS modules, the information flow between different channels of adjacent layer features is enhanced to improve the model's ability to capture target spatial features. In addition, a multi-scale feature fusion mechanism with weighted dual flow paths was adopted to fuse spatial features of different scales, thereby further improving the detection performance of the model at different scales. To validate the performance of the proposed algorithm, we tested it using the RDD2022 dataset. The experimental results show that the enhancement algorithm achieved 84.14% mAP, which is 1.06% higher than the currently advanced YOLOv8 algorithm. Through visualization analysis of the results, it can also be seen that our proposed algorithm has good performance in detecting targets of different scales in complex scenes. The above experimental results demonstrate the effectiveness and superiority of the proposed algorithm, providing valuable insights for advancing real-time road defect detection methods.

Keywords: roads, defect detection, visualization, deep learning

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Authors: Zue Chin Chang, Shih-Chang Liang

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RF magnetron sputtering is used on the ceramic targets, each of which contains zinc oxide (ZnO), zinc oxide doped with aluminum (AZO) and zinc oxide doped with gallium (GZO). The electric conduction mechanism of the AZO and GZO films came mainly from the Al and Ga, the oxygen vacancies, Zn interstitial atoms, and Al and/or Ga interstitial atoms. AZO and GZO films achieved higher conduction than did ZnO film, it being ion vacant and nonstoichiometric. The XRD analysis showed a preferred orientation along the (002) plane for ZnO, AZO, and GZO films.

Keywords: ZnO, AZO, GZO, doped, sputtering

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Authors: Geanderson Eduardo Ambrósio, Dênis Antônio Da Cunha, Marcel Viana Pires

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Historically, human development has been based on economic gains associated with intensive energy activities, which often are exhaustive in the emission of Greenhouse Gases (GHGs). It requires the establishment of targets for mitigation of GHGs in order to disassociate the human development from emissions and prevent further climate change. Brazil presents itself as one of the most GHGs emitters and it is of critical importance to discuss such reductions in intra-national framework with the objective of distributional equity to explore its full mitigation potential without compromising the development of less developed societies. This research displays some incipient considerations about which Brazil’s micro-regions should reduce, when the reductions should be initiated and what its magnitude should be. We started with the methodological assumption that human development and GHGs emissions arise in the future as their behavior was observed in the past. Furthermore, we assume that once a micro-region became developed, it is able to maintain gains in human development without the need of keep growing GHGs emissions rates. The human development index and the carbon dioxide equivalent emissions (CO2e) were extrapolated to the year 2050, which allowed us to calculate when the micro-regions will become developed and the mass of GHG’s emitted. The results indicate that Brazil must throw 300 GT CO2e in the atmosphere between 2011 and 2050, of which only 50 GT will be issued by micro-regions before it’s develop and 250 GT will be released after development. We also determined national mitigation targets and structured reduction schemes where only the developed micro-regions would be required to reduce. The micro-region of São Paulo, the most developed of the country, should be also the one that reduces emissions at most, emitting, in 2050, 90% less than the value observed in 2010. On the other hand, less developed micro-regions will be responsible for less impactful reductions, i.e. Vale do Ipanema will issue in 2050 only 10% below the value observed in 2010. Such methodological assumption would lead the country to issue, in 2050, 56.5% lower than that observed in 2010, so that the cumulative emissions between 2011 and 2050 would reduce by 130 GT CO2e over the initial projection. The fact of associating the magnitude of the reductions to the level of human development of the micro-regions encourages the adoption of policies that favor both variables as the governmental planner will have to deal with both the increasing demand for higher standards of living and with the increasing magnitude of reducing emissions. However, if economic agents do not act proactively in local and national level, the country is closer to the scenario in which emits more than the one in which mitigates emissions. The research highlighted the importance of considering the heterogeneity in determining individual mitigation targets and also ratified the theoretical and methodological feasibility to allocate larger share of contribution for those who historically emitted more. It is understood that the proposals and discussions presented should be considered in mitigation policy formulation in Brazil regardless of the adopted reduction target.

Keywords: greenhouse gases, human development, mitigation, intensive energy activities

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Authors: E. Karacabey, Ş. G. Özçelik, M. S. Turan, C. Baltacıoğlu, E. Küçüköner

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Main concern about deep-fat-fried food materials is their high final oil contents absorbed during frying process and/or after cooling period, since diet including high content of oil is accepted unhealthy by consumers. Different methods have been evaluated to decrease oil content of fried food stuffs. One promising method is partially drying of food material before frying. In the present study it was aimed to control and decrease the final oil content of zucchini slices by means of partial drying and to optimize process conditions. Conventional oven drying was used to decrease moisture content of zucchini slices at a certain extent. Process performance in terms of oil uptake was evaluated by comparing oil content of predried and then fried zucchini slices with those determined for directly fried ones. For predrying and frying processes, oven temperature and weight loss and frying oil temperature and time pairs were controlled variables, respectively. Zucchini slices were also directly fried for sensory evaluations revealing preferred properties of final product in terms of surface color, moisture content, texture and taste. These properties of directly fried zucchini slices taking the highest score at the end of sensory evaluation were determined and used as targets in optimization procedure. Response surface methodology was used for process optimization. The properties, determined after sensory evaluation, were selected as targets; meanwhile oil content was aimed to be minimized. Results indicated that final oil content of zucchini slices could be reduced from 58% to 46% by controlling conditions of predrying and frying processes. As a result, it was suggested that predrying could be one choose to reduce oil content of fried zucchini slices for health diet. This project (113R015) has been supported by TUBITAK.

Keywords: health process, optimization, response surface methodology, oil uptake, conventional oven

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Authors: S. Anastasiou, C. Nathanailides, S. Logothetis, G. Kanlis

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The Greek aquaculture industry is second most important economic sector for the growth of the Greek Economy. The purpose of the present work is to present some data for the management challenges that the Aquaculture industry in Greece is currently facing. Currently the Greek aquaculture industry is going through a series of mergers and restructure. The financial status of the different aquaculture companies, the working conditions and management practices may vary according to lending exposure, market mix, company size, and technological parameters of the different fish farm units and rearing systems. Frequently, the aquaculture personnel are exposed to harsh environmental conditions and to occupational risk. Furthermore, there is pressure on the personnel of fish farms to constantly improve their production efficiency and to enhance their work skills to the new methods and practices which are adopted by the aquaculture industry. There is some data to suggest the existence of gender inequality in the workforce of Greek fish farms. Women are paid less, frequently absent higher managerial positions and most of the male workmates consider the job to harsh for women. Nevertheless, high level of job satisfaction was observed in both men and women. This high level of job satisfaction of the aquaculture personnel can be attributed, at least partially, to the nature of the work which has a very distinct working environment but most of the staff has very positive experiences with the interaction with their workmates and the satisfaction of being in a business which always exceeds its production target. Indeed, there is some evidence to suggest that the Greek aquaculture industry is always exceeding its production targets, while it is rapidly adopting and improving new technology, constantly improving of human resources management practices, which include constant training of the staff, very good communication channels between management and the personnel and reducing the risk of occupational hazard to the aquaculture personnel. All these parameters of management may have a determining role for the volume and quality of the production and future of this sector in Greece.

Keywords: aquaculture, fish quality, management, production targets

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Authors: James Ladzekpo

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Background: The urgent need to identify new pharmacological targets for diabetes treatment and prevention has been amplified by the disease's extensive impact on individuals and healthcare systems. A deeper insight into the biological underpinnings of diabetes is crucial for the creation of therapeutic strategies aimed at these biological processes. Current predictive models based on genetic variations fall short of accurately forecasting diabetes. Objectives: Our study aims to pinpoint key epigenetic factors that predispose individuals to diabetes. These factors will inform the development of an advanced predictive model that estimates diabetes risk from genetic profiles, utilizing state-of-the-art statistical and data mining methods. Methodology: We have implemented a recursive feature elimination with cross-validation using the support vector machine (SVM) approach for refined feature selection. Building on this, we developed six machine learning models, including logistic regression, k-Nearest Neighbors (k-NN), Naive Bayes, Random Forest, Gradient Boosting, and Multilayer Perceptron Neural Network, to evaluate their performance. Findings: The Gradient Boosting Classifier excelled, achieving a median recall of 92.17% and outstanding metrics such as area under the receiver operating characteristics curve (AUC) with a median of 68%, alongside median accuracy and precision scores of 76%. Through our machine learning analysis, we identified 31 genes significantly associated with diabetes traits, highlighting their potential as biomarkers and targets for diabetes management strategies. Conclusion: Particularly noteworthy were the Gradient Boosting Classifier and Multilayer Perceptron Neural Network, which demonstrated potential in diabetes outcome prediction. We recommend future investigations to incorporate larger cohorts and a wider array of predictive variables to enhance the models' predictive capabilities.

Keywords: diabetes, machine learning, prediction, biomarkers

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Authors: Maryam Zahmatkesh

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Middle managers form a significant occupational category in organisations. They undertake a vital role, as they sit between the operational and strategic roles. Traditionally they were acting as diplomat administrators, and were only in power to meet the demands of professionals. Following the introduction of internal market, in line with the principles of New Public Management, middle managers have been considered as change agents. More recently, in the debates of middle managers, there is emphasis on entrepreneurialism and enacting strategic role. It was assumed that granting autonomy to the local organisations and the inception of semi-autonomous hospitals (Foundation Trusts in England and Board of Trustees in Iran) would give managers more autonomy to act proactively and innovatively. This thesis explores the hospital middle managers’ perception of and responses to public management reforms (in particular, hospital autonomy) in England and Iran. In order to meet the aims of the thesis, research was undertaken within the interpretative paradigm, in line with social constructivism. Data were collected from interviews with forty-five middle managers, observational fieldwork and documentary analysis across four teaching university hospitals in England and Iran. The findings show the different ways middle managers’ autonomy is constrained in the two countries. In England, middle managers have financial and human recourses, but their autonomy is constrained by government policy and targets. In Iran, middle managers are less constrained by government policy and targets, but they do not have financial and human resources to exercise autonomy. Unbalanced autonomy causes tension and frustration for middle managers. According to neo-institutional theory, organisations are deeply embedded within social, political, economic and normative settings that exert isomorphic and internal population-level pressures to conform to existing and established modes of operation. Health systems which are seeking to devolve autonomy to middle managers must appreciate the multidimensional nature of the autonomy, as well as the wider environment that organisations are embedded, if they are about to improve the performance of managers and their organisations.

Keywords: autonomy, healthcare organisations, middle managers, new public management

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Authors: Shanakr Bhattarai, V. S. Tiwari, Barak Akabayov

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The plummeting number of infections and death is due to the development of drug-resistant bacteria. In addition, the number of approved antibiotic drugs by the Food and Drug Administration (FDA) is insufficient. Therefore, developing new drugs and finding novel targets for central metabolic pathways in bacteria is urgently needed. One of the promising targets is DNA replication machinery which consists of many essential proteins and enzymes. DnaG primase is an essential enzyme and a central part of the DNA replication machinery. DnaG primase synthesizes short RNA primers that initiate the Okazaki fragments by the lagging strand DNA polymerase. Therefore, it is reasonable to assume that inhibition of primase activity will stall DNA replication and prevent bacterial proliferation. We did the expression and purification of eight different bacterial DnaGs (Mycobacterium tuberculosis(Mtb), Bacillus anthracis (Ba), Mycobacterium smegmatis (Msmeg), Francisella tularencis (Ft), Vibrio cholerae (Vc) and Yersinia pestis (Yp), Staphylococcus aureus(Saureus), Escherichia coli(Ecoli)) followed by the radioactive activity assay. After obtaining the pure and active protein DnaG, we synthesized the inhibitors for them. The inhibitors were divided into five different groups, each containing five molecules, and the cocktail inhibition assay was performed against each DnaGs. The groups of molecules inhibiting the DnaGs were further tested with individual molecules belonging to inhibiting groups. Each molecule showing inhibition was titrated against the corresponding DnaGs to find IC50. We got a molecule(VS167) that acted as broad inhibitors, inhibiting all eight DnaGs. Molecules VS180 and VS186 inhibited seven DnaGs (except Saureus). Similarly, two molecules(VS 173, VS176) inhibited five DnaGs (Mtb, Ba, Ft, Yp, Ecoli). VS261 inhibited four DnaGs (Mtb, Ba, Ft, Vc). MS50 inhibited Ba and Vc DnaGs. And some of the inhibitors inhibited only one DnaGs. Thus we found the broad and specific inhibitors for different bacterial DnaGs, and their Structure-activity analysis(SAR) was done. Further, We tried to explain the similarities among the enzyme DnaGs from different bacteria based on their inhibition pattern.

Keywords: DNA replication, DnaG, okazaki fragments, antibiotic drugs

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Authors: Sarah Potter, Michele Laliberte

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As eating disorders are associated with high levels of chronicity, impairment, and distress, it is paramount to evaluate factors that may improve treatment outcomes in this group. Individuals with eating disorders exhibit elevated levels of perfectionism and emotion dysregulation, as well as reduced self-compassion. These variables are related to eating disorder outcomes, including shape/weight concerns and psychosocial impairment. Thus, these factors may be tenable targets for treatment within eating disorder populations. However, the relative contributions of perfectionism, emotion dysregulation, and self-compassion to the severity of shape/weight concerns and psychosocial impairment remain largely unexplored. In the current study, mediation analyses were conducted to clarify how perfectionism, emotion dysregulation, and self-compassion are linked to shape/weight concerns and psychosocial impairment. The sample was comprised of 85 patients from an outpatient eating disorder clinic. The patients completed self-report measures of perfectionism, self-compassion, emotion dysregulation, eating disorder symptoms, and psychosocial impairment. Specifically, emotion dysregulation was assessed as a mediator in the relationships between (1) perfectionism and shape/weight concerns, (2) self-compassion and shape/weight concerns, (3) perfectionism and psychosocial impairment, and (4) self-compassion and psychosocial impairment. It was postulated that emotion dysregulation would significantly mediate relationships in the former two models. An a priori hypothesis was not constructed in reference to the latter models, as these analyses were preliminary and exploratory in nature. The PROCESS macro for SPSS was utilized to perform these analyses. Emotion dysregulation fully mediated the relationships between perfectionism and eating disorder outcomes. In the link between self-compassion and psychosocial impairment, emotion dysregulation partially mediated this relationship. Finally, emotion dysregulation did not significantly mediate the relationship between self-compassion and shape/weight concerns. The results suggest that emotion dysregulation and self-compassion may be suitable targets to decrease the severity of psychosocial impairment and shape/weight concerns in individuals with eating disorders. Further research is required to determine the stability of these models over time, between diagnostic groups, and in nonclinical samples.

Keywords: eating disorders, emotion dysregulation, perfectionism, self-compassion

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Authors: Magdy Danial Riad

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Introduction: The ability of our world to support the expanding population after 2050 is at risk due to the food system's global role in poor health, climate change, and resource depletion. Healthy, equitable, and sustainable food systems must be achieved from the point of production through consumption in order to meet several of the sustainable development goals (SDG) targets. There is evidence that changing the local food environment can effectively change dietary habits in a community. The purpose of this article is to outline the policy initiatives taken by local governments to support environmentally friendly eating habits. Methods: Five databases were searched for peer-reviewed articles that described local government authorities' implementation of environmentally sustainable eating habits, were located in cities that had signed the Milan Urban Food Policy Pact, were published after 2015, were available in English, and described policy interventions. Data extraction was a two-step approach that started with extracting information from the included study and ended with locating information unique to policies in the grey literature. Results: 45 papers that described a variety of policy initiatives from low-, middle-, and high-income countries met the inclusion criteria. A variety of desired dietary behaviors were the focus of policy action, including reducing food waste, procuring food locally and in season, boosting breastfeeding, avoiding overconsumption, and consuming more plant-based meals and fewer items derived from animals. Conclusions: In order to achieve SDG targets, local governments are under pressure to implement evidence-based interventions. This study can help direct local governments toward evidence-based policy measures to improve regional food systems and support ecologically friendly eating habits.

Keywords: meals, planet, poor health, eating habits

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Authors: Pawel Kiper, Alfonc Baba, Mahmoud Alhelou, Giorgia Pregnolato, Michela Agostini, Andrea Turolla

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Impairment of cervical spine mobility is often related to pain triggered by musculoskeletal disorders or direct traumatic injuries of the spine. To date, these disorders are assessed with goniometers and inclinometers, which are the most popular devices used in clinical settings. Nevertheless, these technologies usually allow measurement of no more than two-dimensional range of motion (ROM) quotes in static conditions. Conversely, the wide use of motion tracking systems able to measure 3 to 6 degrees of freedom dynamically, while performing standard ROM assessment, are limited due to technical complexities in preparing the setup and high costs. Thus, motion tracking systems are primarily used in research. These systems are an integral part of virtual reality (VR) technologies, which can be used for measuring spine mobility. To our knowledge, the accuracy of VR measure has not yet been studied within virtual environments. Thus, the aim of this study was to test the reliability of a protocol for the assessment of sensorimotor function of the cervical spine in a population of healthy subjects and to compare whether using immersive or non-immersive VR for visualization affects the performance. Both VR assessments consisted of the same five exercises and random sequence determined which of the environments (i.e. immersive or non-immersive) was used as first assessment. Subjects were asked to perform head rotation (right and left), flexion, extension and lateral flexion (right and left side bending). Each movement was executed five times. Moreover, the participants were invited to perform head reaching movements i.e. head movements toward 8 targets placed along a circular perimeter each 45°, visualized one-by-one in random order. Finally, head repositioning movement was obtained by head movement toward the same 8 targets as for reaching and following reposition to the start point. Thus, each participant performed 46 tasks during assessment. Main measures were: ROM of rotation, flexion, extension, lateral flexion and complete kinematics of the cervical spine (i.e. number of completed targets, time of execution (seconds), spatial length (cm), angle distance (°), jerk). Thirty-five healthy participants (i.e. 14 males and 21 females, mean age 28.4±6.47) were recruited for the cervical spine assessment with immersive and non-immersive VR environments. Comparison analysis demonstrated that: head right rotation (p=0.027), extension (p=0.047), flexion (p=0.000), time (p=0.001), spatial length (p=0.004), jerk target (p=0.032), trajectory repositioning (p=0.003), and jerk target repositioning (p=0.007) were significantly better in immersive than non-immersive VR. A regression model showed that assessment in immersive VR was influenced by height, trajectory repositioning (p<0.05), and handedness (p<0.05), whereas in non-immersive VR performance was influenced by height, jerk target (p=0.002), head extension, jerk target repositioning (p=0.002), and by age, head flex/ext, trajectory repositioning, and weight (p=0.040). The results of this study showed higher accuracy of cervical spine assessment when executed in immersive VR. The assessment of ROM and kinematics of the cervical spine can be affected by independent and dependent variables in both immersive and non-immersive VR settings.

Keywords: virtual reality, cervical spine, motion analysis, range of motion, measurement validity

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Authors: M. R. Rouhi, S. Shafiei, A. Taghavipour, H. Adibi-Asl, A. Doosthoseini

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This research targets at alleviating the problem of range anxiety associated with the battery electric vehicles (BEVs) by considering mechanical and control aspects of the powertrain. In this way, all the energy consuming components and their effect on reducing the range of the BEV and battery life index are identified. On the other hand, an appropriate control strategy is designed to guarantee the performance of the BEV and the extended electric range which is evaluated by an extensive simulation procedure and a real-world driving schedule.

Keywords: battery, electric vehicles, ultra-capacitor, model predictive control

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Authors: Rahaba Marima, Clement Penny

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The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

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