Search results for: Kynurenine pathway

Authors: Cian O'Shea, Ross O'Halloran, Peter Haigh

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Wireless Sensor Networks (WSN) are Internet of Things (IoT) edge devices. They are becoming widely adopted in many industries, including health care, building energy management, and conditional monitoring. As the scale of WSN deployments increases, the cost and complexity of battery replacement and disposal become more significant and in time may become a barrier to adoption. Harvesting ambient energies provide a pathway to reducing dependence on batteries and in the future may lead to autonomously powered sensors. This work describes a simulation tool that enables the user to predict the battery life of a wireless sensor that utilizes energy harvesting to supplement the battery power. To create this simulator, all aspects of a typical WSN edge device were modelled including, sensors, transceiver, and microcontroller as well as the energy source components (batteries, solar cells, thermoelectric generators (TEG), supercapacitors and DC/DC converters). The tool allows the user to plug and play different pre characterized devices as well as add user-defined devices. The goal of this simulation tool is to predict the lifetime of a device and scope for extension using ambient energy sources.

Keywords: Wireless Sensor Network, IoT, edge device, simulation, solar cells, TEG, supercapacitor, energy harvesting

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Authors: Musa Mayanja Lwanga, Annet Adong

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This study provides a micro perspective on the impact of mobile money services on individual’s saving behavior using the 2013 Uganda FinScope data. Results show that although saving through the mobile phone is not a common practice in Uganda, being a registered mobile money user increases the likelihood to save with mobile money. Saving using mobile is more prevalent in urban areas and in Kampala and Central region compared to other regions. This can be explained by: first, rural dwellers tend on average to have lower incomes and thus have lower to saving compared to the urban counterpart. Similarly, residents of Kampala tend to have higher incomes and thus high savings compared to residents of other regions. Secondly, poor infrastructure in rural areas in terms of lack of electricity and poor telecommunication network coverage may limit the use of mobile phones and consequently the use of mobile money as a saving mechanism. Overall, the use of mobile money as a saving mechanism is still very low and this could be partly explained by limitations in the legislation that does not incorporate mobile finance services into mobile money. The absence of interest payments on mobile money savings may act as a disincentive to save through this mechanism. Given the emerging mobile banking services, there is a need to create more awareness and the need for enhanced synergies between telecom companies and commercial banks.

Keywords: financial inclusion, mobile money, savings, Uganda

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Authors: Karthik Mittal

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This study performs an unsupervised machine learning analysis to find clusters of related SNPs which highlight biological pathways that are important for the biological mechanisms of breast cancer. Studying genetic variations in isolation is illogical because these genetic variations are known to modulate protein production and function; the downstream effects of these modifications on biological outcomes are highly interconnected. After extracting the SNPs and their effect on different types of breast cancer using the MRBase library, two unsupervised machine learning clustering algorithms were implemented on the genetic variants: a k-means clustering algorithm and a hierarchical clustering algorithm; furthermore, principal component analysis was executed to visually represent the data. These algorithms specifically used the SNP’s beta value on the three different types of breast cancer tested in this project (estrogen-receptor positive breast cancer, estrogen-receptor negative breast cancer, and breast cancer in general) to perform this clustering. Two significant genetic pathways validated the clustering produced by this project: the MAPK signaling pathway and the connection between the BRCA2 gene and the ESR1 gene. This study provides the first proof of concept showing the importance of unsupervised machine learning in interpreting GWAS summary statistics.

Keywords: breast cancer, computational biology, unsupervised machine learning, k-means, PCA

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Authors: Methawee Yuttapongtada

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Intensifier is the linguistic term and device that is generally found in different languages in order to enhance and give additional quantity, quality or emotion to the words of each language. In fact, each language in the world has both of the similar and dissimilar intensifying device. More specially, the wide variety of intensifying device is used for Thai language and one of those is usage of the impolite word or the word that used to mean something negative as intensifier. The data collection in this study was done throughout the spoken language style by collecting from intensifiers regarded as impolite words because these words as employed in the other contexts will be held as the rude, swear words or the words with negative meaning. Then, backward study to the past was done in order to consider the historical change. Explanation of the original meaning and the contexts of words use from the past till the present time were done by use of both textual documents and dictionaries available in different periods. It was found that regarding the semantics and pragmatic aspects, subjectification also is the significant motivation that changed the impolite words to intensifiers. At last, it can explain pathway of the semantic change of these very words undoubtedly. Moreover, it is found that use tendency in the impolite word or the word that used to mean something negative will more be increased and this phenomenon is commonly found in many languages in the world and results of this research may support to the belief that human language in the world is universal and the same still reflected that human has the fundamental thought as the same to each other basically.

Keywords: impolite word, intensifier, Thai, semantic change

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Authors: Sónia Ribeiro, Diana Farinha, Hélia Sales, Rita Pontes, João Nunes

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The demand and commitment to sustainability in the agrifood sector introduce news opportunities for new composite materials. Composite materials are emerging as a vital entity for the sustainable development. Polylactic acid (PLA) has been recognized as a potential polymer with attractive characteristics for agrifood sector applications. PLA that can be beneficial for the development of composites, biocomposites, films, porous gels, and so on. The production of PLA from lignocellulosic biomass residues matrix is a key option towards a sustainable and circular bioeconomy and a non-competitive application with feed and food sector. The Flui and BeirInov projects presents news developments in the production of PLA composites to value the Portuguese forest ecosystem, with high amount of lignocellulosic biomass residues and available. A performance production of lactic acid from lignocellulosic biomass undergoes a process of autohydrolysis, saccharification and fermentation, originating a lactic acid fermentation medium with a 72.27g.L-1 was obtained and a final purification of 72%. The high purification PLA from multi lignocellulosic residues representing one economic expensive process, and a new materials and application for the polymers and a combination with others types of composites matrix characteristic is the drive-up for this green market.

Keywords: polylactic acid, lignocellulosic biomass, agrifood, composite materials

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Authors: Munir Majdalawieh, Adam Marks

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In today’s very competitive higher education industry (HEI), HEIs are faced with the primary concern of developing, deploying, and sustaining high quality academic programs. Today, the HEI has well-established accreditation systems endorsed by a country’s legislation and institutions. The accreditation system is an educational pathway focused on the criteria and processes for evaluating educational programs. Although many aspects of the accreditation process highlight both the past and the present (prove), the “program review” assessment is "forward-looking assessment" (improve) and thus transforms the process into a continuing assessment activity rather than a periodic event. The purpose of this study is to propose a conceptual measurement framework for program review to be used by HEIs to undertake a robust and targeted approach to proactively and continuously review their academic programs to evaluate its practicality and effectiveness as well as to improve the education of the students. The proposed framework consists of two main components: program review principles and the program review measurement matrix.

Keywords: academic program, program review principles, curriculum development, accreditation, evaluation, assessment, review measurement matrix, program review process, information technologies supporting learning, learning/teaching methodologies and assessment

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Authors: Chloe T. Cohen, Sarah Johnson

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Psychoanalytic literature has traditionally focused on the theoretical explanations of psychological phenomena rather than empirical research to support those ideas. Many clinicians assume a lack of empirical verification of the theories that underpin psychoanalytic treatment disqualifies psychoanalytic psychotherapy as an effective clinical technique. One such theory is Lacan’s ‘Name of the Father’, which extended Freud’s idea of the importance of a successful resolution of the Oedipal problem, situating it even earlier in psychological development. Lacan posited that the Name of the Father construct (establishing psychological structure and preventing psychosis) was best represented in language use, metaphor, and linguistic structure. However, no study to date has empirically examined the Name of the Father construct. The current study attempts to measure Lacan’s ‘Name of the Father’ construct through linguistic structure and metaphor use and to compare it with Freud’s ‘original introject’. We will then investigate whether they relate to adult personality functioning (measured using the Rorschach Inkblot Test). We aim to contribute to the empirical study of psychoanalytic concepts by operationalizing and validating the Name of the Father empirically. We also aim to examine the relationship of the Name of the Father construct to Freud’s concept of the original introject and to adult pathology. We hypothesize that measures of the original introject will mediate the pathway between linguistic indicators of Lacan’s Name of the Father construct and personality functioning.

Keywords: Lacan, Name of the Father, original introject, personality functioning, psychoanalysis

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Authors: Harminder Kaur, Manpreet Kaur, Akanksha Kapila, Reenu

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Schiff base with general formula H₂L was derived from condensation of o-vanillin and 3-nitro-o-phenylenediamine. This Schiff base was used for the synthesis of organotin(IV) complexes with general formula R₂SnL [R=Phenyl or n-octyl] using equimolar quantities. Elemental analysis UV-Vis, FTIR, and multinuclear spectroscopic techniques (¹H, ¹³C, and ¹¹⁹Sn) NMR were carried out for the characterization of the synthesized complexes. These complexes were coloured and soluble in polar solvents. Computational studies have been performed to obtain the details of the geometry and electronic structures of ligand as well as complexes. Geometry of the ligands and complexes have been optimized at the level of Density Functional Theory with B3LYP/6-311G (d,p) and B3LYP/MPW1PW91 respectively followed by vibrational frequency analysis using Gaussian 09. Observed ¹¹⁹Sn NMR chemical shifts of one of the synthesized complexes showed tetrahedral geometry around Tin atom which is also confirmed by DFT. HOMO-LUMO energy distribution was calculated. FTIR, ¹HNMR and ¹³CNMR spectra were also obtained theoretically using DFT. Further IRC calculations were employed to determine the transition state for the reaction and to get the theoretical information about the reaction pathway. Moreover, molecular docking studies can be explored to ensure the anticancer activity of the newly synthesized organotin(IV) complexes.

Keywords: DFT, molecular docking, organotin(IV) complexes, o-vanillin, 3-nitro-o-phenylenediamine

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Authors: Khaled S. Al Salhen

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Aldehyde oxidase is molybdo-flavoenzyme involved in the oxidation of hundreds of endogenous and exogenous and N-heterocyclic compounds and environmental pollutants. Uncharged N-heterocyclic aromatic compounds such phenanthridine are commonly distributed pollutants in soil, air, sediments, surface water and groundwater, and in animal and plant tissues. Phenanthridine as uncharged N-heterocyclic aromatic compound was incubated with partially purified aldehyde oxidase from rainbow trout fish liver. Reversed-phase HLPC method was used to separate the oxidation products from phenanthridine and the metabolite was identified. The 6(5H)-phenanthridinone was identified the major metabolite by partially purified aldehyde oxidase from fish liver. Kinetic constant for the oxidation reactions were determined spectrophotometrically and showed that this substrate has a good affinity (Km = 78 ± 7.6 µM) for hepatic aldehyde oxidase, coupled with a relatively high oxidation rate (0.77± 0.03 nmol/min/mg protein). In addition, the kinetic parameters of hepatic fish aldehyde oxidase towards the phenanthridine substrate indicate that in vitro biotransformation by hepatic fish aldehyde oxidase will be a significant pathway. This study confirms that partially purified aldehyde oxidase from fish liver is indeed the enzyme responsible for the in vitro production 6(5H)-phenanthridinone metabolite as it is a major metabolite by mammalian aldehyde oxidase.

Keywords: aldehyde oxidase, fish, phenanthridine, specificity

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Authors: Kazui Sasakii, Seira Mormune-Moriya, Hiroaki Tanahashi, Shigeji Kongaya

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Poly (3.4-ethylenedioxythiophene) doped with poly (4-styrene sulfonate) (PEDOT: PSS) attracted a great deal of attention because of its unique characteristics of flexibility, optical properties, heat resistance and colloidal dispersion in water. It is well known that when high boiling solvents such as ethylene glycol or dimethyl sulfoxide are added as a secondary dopant to the micellar structure, PEDOT microcrystallizes and becomes highly conductive. In previous study bis(4-hydroxyphenyl) sulfone (BPS) was used as a secondary dopant for PEDOT:PSS and the enhancement of the conductivity was revealed. However, ductility is one of the serious issues which limited the application of PEDOT:PSS/BPS. So far, the composition with polymer binders has been conducted, however, polymer binders decrease the conductivity of the materials. In this study, PEDOT: PSS composites with polyester (PEs) were prepared by a simple aqueous process using PEs emulsion. The structural studies revealed that PEDOT:PSS and PEs were homogeneously distributed in the composites. It was found that the properties of PEDOT:PSS were remarkably enhanced by the incorporation of PEs. According to the tensile test, the ductility of PEDOT:PSS was remarkably improved. Interestingly, the conductivity of PEDOT:PSS/PEs composites was higher than that of neat PEDOT:PSS. For example, the conductivity increased by 8% at PEs content of 25 wt%. Since PEDOT:PSS were homogeneously dispersed on the surface of PEs particles, it was assumed that the conductive pathway was constructed by PEs particles in the nanocomposites. Therefore, a significant increase in conductivity was achieved.

Keywords: polymer composites, conductivity, PEDOT:PSS, polyester

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Authors: Christos Bouras, Eirini Stergiou, Charitini Karakostaki, Vasileios Tzanos, Vasileios Kokkinos

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Wind power represents a major pathway to curtailing greenhouse gas emissions and thus reducing the rate of climate change. A wind turbine runs practically emission-free for 20 years, representing one of the most environmentally sustainable sources of energy. Nevertheless, environmental and biodiversity concerns can often slow down or halt the deployment of wind farms due to local public opposition. This opposition is often fueled by poor relationships between wind energy stakeholders and civil society, which in many cases led to conflictual protests and property damage. In this context, addressing these concerns is essential in order to facilitate the proliferation of wind farms in Europe and the phase-out of fossil fuels from the energy mix. The aim of this study is to identify a number of good practices and cases to avoid increasing biodiversity protection at all stages of wind farms’ lifecycle in three participating countries, namely Greece, Latvia, and Poland. The results indicate that although available technological solutions are already being exploited worldwide, in these countries, there is still room for improvement. To address this gap, a set of policy recommendations is proposed to accomplish the wind energy targets in the near future while simultaneously mitigating the pertinent biodiversity risks.

Keywords: biodiversity protection, environmental impact, social acceptance, wind energy

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Authors: Kimuli Ismail, Michael Lubwama, John Baptist Kirabira, Adam Sebbit

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This study develops 4 energy scenarios for Greater Kampala Metropolitan Area (GKMA). GKMA is Uganda’s capital with a population of 4.1million and a GDP growth rate of 5.8 with a nonsustainable energy management system. The study uses TIMES-VEDA to examine the energy impacts of business as usual (BAU), Kabejja, Carbon-Tax, and Lutta scenarios in commercial, industrial, transportation, residential, agricultural, and electricity generation activities. BAU is the baseline scenario with limited CO2 emissions restrictions against which Kabejja with 20% CO2 emissions restriction, a carbon tax of $100/ton imposed in 2050 for Carbon-Tax scenario, and Lutta with 95% CO2 emissions restriction is made. The analysis suggests that if the current policy trends continue as BAU, consumption would increase from 139.6PJ to 497.42PJ and CO2 emissions will increase from 4.6mtns to 7mtns. However, consumption would decrease by 2.3% in Kabejja, 3.4% in Carbon-Tax, and 3.3 % in Lutta compared to BAU. The CO2 emissions would decrease by 8.57% in Kabejja, 55.14% in Carbon-Tax, and 60% in Lutta compared to BAU. Sustainability is achievable when low-carbon electricity is increased by 53.68% in the EMS, and setting up an electrified Kampala metro. The study recommends Lutta as the sustainable pathway to a lowcarbon 2050.

Keywords: Sustainability, Scenario Plannnig, Times-Veda Modelling, Energy Policy Development

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Authors: Zi-Han Li, Lu Fang, Liang Wu, Dong-Yuan Chang, Manyuan Dong, Liang Ji, Qi Zhang, Ming-Hui Zhao, Sydney C. W. Tang, Lemin Zheng, Min Chen

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Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia, which were risk factors for diabetic nephropathy (DN). Recently, we found that ANXA1 could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, we identified uncoupling protein 1 (UCP1), an inner membrane protein of mitochondria, as a key to mitochondrial homeostasis improved by ANXA1. Specifically, ANXA1 attenuated mitochondrial dysfunction via appropriately upregulating UCP1 by stabilizing its transcription factor GATA binding protein 3 (GATA3) by combining it with thioredoxin. Moreover, specific overexpression of UCP1 in the renal cortex rescued renal injuries in diabetic Anxa1-KO mice. UCP1 deletion aggravated renal injuries in HFD/STZ-induced diabetic mice. Mechanistically, UCP1 reduced mitochondrial fission through the aristaless-related homeobox (ARX)/cardiolipin synthase 1 (CRLS1) pathway. Therapeutically, CL316243, a UCP1 agonist, could attenuate established DN in db/db mice. This work established an alternative principle to harness the power of uncouplers for the treatment of DN.

Keywords: diabetic nephropathy, uncoupling protein 1, mitochondrial homeostasis, cardiolipin metabolism

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Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

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Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

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Authors: Shan-Ying Wu, Sheng-Hui Lan, Xi-Zhang Lin, Ih-Jen Su, Ting-Fen Tsai, Chia-Jui Yen, Tsung-Hsueh Lu, Fu-Wen Liang, Huey-Jen Su, Chun-Li Su, Hsiao-Sheng Liu

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In hepatocelluar carcinoma (HCC), dysregulated expression of cyclin D1 and impaired autophagy has been reported separately. However, the relationship between them has not been explored. In this study, we demonstrated that autophagy was inversely correlated with cyclin D1 expression in 147 paired HCC patient specimens. HCC specimen with highly expression of cyclin D1 shows correlation with poor overall survival rate. Furthermore, induction of autophagy by amiodarone (antiarrhythmic drug) in Hep 3B cells, cyclin D1 was recruited into autophagosomes demonstrated by immune-gold labeling of cyclin D1 after extraction of autophagosomes. We further demonstrated that autophagy suppresses Hep 3B cell proliferation, and further analysis revealed that cell cycle was arrested at G1 phase. The interaction between LC3 (maker of autophagy) and cyclin D1 was increased after autophagy induction. In addition, ubiquitinated-cyclin D1 was also increased after autophagy induction, which is selectively degraded by autophagosome through binding with SQSTM1/p62 (an adaptor protein). In vivo study showed that amiodarone induced autophagy suppresses liver tumor formation in xenograft mouse and orthotopic rat model through decreasing cyclin D1 expression and inhibition of cell proliferation. Altogether, we reveal a novel mechanism that ubiquitinated cyclin D1 degraded by autophagic pathway by p62 and amiodarone is a promising drug for targeting cyclin D1 in liver cancer therapy.

Keywords: autophagy, cyclin D1, hepatocellular carcinoma, amiodarone

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Authors: Zi-Han Li, Lu Fang, Liang Wu, Dong-Yuan Chang, Manyuan Dong, Liang Ji, Qi Zhang, Ming-Hui Zhao, Sydney C.W. Tang, Lemin Zheng, Min Chen

Abstract:

Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia, which were risk factors for diabetic nephropathy (DN). Recently, it was found that annexin A1(ANXA1) could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, it was identified that uncoupling protein 1 (UCP1), an inner membrane protein of mitochondria, as a key to mitochondrial homeostasis improved by ANXA1. Specifically, ANXA1 attenuated mitochondrial dysfunction via appropriately upregulating UCP1 by stabilizing its transcription factor GATA binding protein 3 (GATA3) through combining with thioredoxin. Moreover, specific overexpression of UCP1 in renal cortex rescued renal injuries in diabetic Anxa1-KO mice. UCP1 deletion aggravated renal injuries in HFD/STZ-induced diabetic mice. Mechanistically, UCP1 reduced mitochondrial fission through the aristaless-related homeobox (ARX)/cardiolipin synthase 1 (CRLS1) pathway. Therapeutically, CL316243, a UCP1 agonist, could attenuate established DN in db/db mice. This work established a novel principle to harness the power of uncouplers for the treatment of DN.

Keywords: diabetic nephropathy, uncoupling protein 1, mitochondrial homeostasis, cardiolipin metabolism

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Authors: Ashish Kumar Pathak, Ritika Sharma, Vishal Nath, Sudhir Pratap Singh, Rakesh Tuli

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Litchi is a sub-tropical fruit crop with genotypes bearing delicious juicy fruits with variable seed size (bold to rudimentary size). Small seed size is a desirable trait in litchi, as it increases consumer acceptance and fruit processing. The biochemical activities in mid- stage ovules (e.g. 16, 20, 24 and 28 days after anthesis) determine the fate of seed and fruit development in litchi. Comprehensive ovule-specific transcriptome analysis was performed in two litchi genotypes with contrasting seed size to gain molecular insight on determinants of seed fates in litchi fruits. The transcriptomic data was de-novo assembled in 1,39,608 trinity transcripts, out of which 6,325 trinity transcripts were differentially expressed between the two contrasting genotypes. Differential transcriptional pattern was found among ovule development stages in contrasting litchi genotypes. The putative genes for salicylic acid, jasmonic acid and brassinosteroid pathway were down-regulated in ovules of small-seeded litchi. Embryogenesis, cell expansion, seed size and stress related trinity transcripts exhibited altered expression in small-seeded genotype. The putative regulators of seed maturation and seed storage were down-regulated in small-seed genotype.

Keywords: Litchi, seed, transcriptome, defence

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Authors: Pui Shan Wong, Kosuke Tashiro, Satoru Kuhara, Sachiyo Aburatani

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Functional genomics and gene regulation inference has readily expanded our knowledge and understanding of gene interactions with regards to expression regulation. With the advancement of transcriptome sequencing in time-series comes the ability to study the sequential changes of the transcriptome. This method presented here works to augment existing regulation networks accumulated in literature with transcriptome data gathered from time-series experiments to construct a sequential representation of transcription factor activity. This method is applied on a time-series RNA-Seq data set from Escherichia coli as it transitions from growth to stationary phase over five hours. Investigations are conducted on the various metabolic activities in gene regulation processes by taking advantage of the correlation between regulatory gene pairs to examine their activity on a dynamic network. Especially, the changes in metabolic activity during phase transition are analyzed with focus on the pagP gene as well as other associated transcription factors. The visualization of the sequential transcriptional activity is used to describe the change in metabolic pathway activity originating from the pagP transcription factor, phoP. The results show a shift from amino acid and nucleic acid metabolism, to energy metabolism during the transition to stationary phase in E. coli.

Keywords: Escherichia coli, gene regulation, network, time-series

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Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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Authors: Y. S. Mohamed, L. A. Ahmed, H. A. Salem, A. M. Agha

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Liver Fibrosis is one of the most serious conditions that affect the Egyptian society. In the present study, the effect of nicorandil was investigated in experimentally-induced liver fibrosis by bile duct ligation in rats. Nicorandil (3mg/kg/day) was given orally 24 h after bile duct ligation for 14 days till the end of the experiment. Nicorandil group showed a significant improvement in liver function tests (ALT and ALP) as well as a significant decrease in oxidative stress biomarkers (TBARS and GSH), area of fibrosis and activity of hepatic stellate cells as indicated by decreased expression of alpha smooth muscle actin.Moreover, nicorandil treatment decreased HSCs proliferation due to its inhibitory effects on protein kinase C(PKC) and Platelet derived growth factor (PDGF) . Oral administration of either glibenclamide (10 mg/kg/day)(a KATP channel blocker) or L-NAME (30 mg/kg/day) (an inhibitor of nitric oxide synthase) blocked the protective effects of nicorandil. However, nicorandil and L-NAME treated group showed more or less results similar to that of untreated bile duct ligated group. In conclusion, nicorandil was effective against the development of bile duct ligated-induced liver fibrosis in rats where activation of the NO pathway plays an important role in the protective effect nicorandil.

Keywords: hepatic stellate cells, nicorandil, nitric oxide donor, liver fibrosis

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Authors: A. Duncan, A. Blake, A. O'Gara, J. Fitzgerald

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Introduction: Acute traumatic rib fractures have significant morbidity and mortality and are a commonly seen injury in trauma patients. Rib fracture pain can often be acute and can prove challenging to manage. We performed an audit on patients with acute traumatic rib fractures with the aim of composing a referral and treatment pathway for such patients. Methods: From January 2021 to January 2022, the pain medicine service encouraged early referral of all traumatic rib fractures to the pain service for a multi-modal management approach. A retrospective audit of analgesic management was performed on a select cohort of 24 patients, with a mean age of 67, of which 19 had unilateral rib fractures. Results: 17 of 24 patients (71%) underwent local, regional block as part of a multi-modal analgesia regime. Only one regional complication was observed, seen with hypotension occurring in one patient with a thoracic epidural. The group who did not undergo regional block had a length of stay (LOS) 17 days longer than those who did (27 vs. 10) and higher rates of pneumonia (29% vs. 18%). Conclusion: Early referral to pain specialists is an important component of the effective management of acute traumatic rib fractures. From our audit, it is evident that regional blocks can be effectively used in these cases as part of a multi-modal analgesia regime and may confer benefits in terms of respiratory complications and length of stay.

Keywords: rib fractures, regional blocks, thoracic epidural, erector spina block

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Authors: Orapan Paecharoenchai, Tanasait Ngawhirunpat, Theerasak Rojanarata, Auayporn Apirakaramwong, Praneet Opanasopit

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Cationic niosomes formulated with Span20, cholesterol and novel synthesized spermine-cationic lipids (2-hydrocarbon tail and 4- hydrocarbon tail) in a molar ratio of 2.5:2.5:1 can mediate high gene transfection in vitro. However, the uptake mechanisms of these systems are not well clarified. In the present study, effect of endocytic inhibitors on the transfection efficiency of niosomes/DNA complexes was determined on a human cervical carcinoma cell line (HeLa cells) using the inhibitors of macropinocytosis (wortmannin), clathrin- and caveolae-mediated endocytosis (methyl-β-cyclodextrin), clathrin-mediated endocytosis (chlorpromazine), caveolae-mediated endocytosis (genistein and filipin), cytosolic transfer (ammonium chloride) and microtubules polymerization (nocodazole). The transfection of niosomes with 2-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride and filipin, respectively, whereas, the transfection of niosomes with 4-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride, methyl-β-cyclodextrin and filipin, respectively. It can be concluded that these niosomes/DNA complexes were internalized predominantly by endocytosis via clathrin and caveolae-independent pathway.

Keywords: cellular internalization, cationic niosomes, gene carriers, spermine-cationic lipids

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Authors: Saroj Poudel, Joshua Mancini, Douglas Pike, Jennifer Timm, Alexei Tyryshkin, Vikas Nanda, Paul Falkowski

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On the early Earth, protein-metal complexes likely harvested energy from a reduced environment. These complexes would have been precursors to the metabolic enzymes of ancient organisms. Hydrogenase is an essential enzyme in most anaerobic organisms for the reduction and oxidation of hydrogen in the environment and is likely one of the earliest evolved enzymes. To attempt to reinvent a precursor to modern hydrogenase, we computationally designed a short thirteen amino acid peptide that binds the often-required catalytic transition metal Nickel in hydrogenase. This simple complex can achieve hundreds of hydrogen evolution cycles using light energy in a broad range of temperature and pH. Biophysical and structural investigations strongly indicate the peptide forms a di-nickel active site analogous to Acetyl-CoA synthase, an ancient protein central to carbon reduction in the Wood-Ljungdahl pathway and capable of hydrogen evolution. This work demonstrates that prior to the complex evolution of multidomain enzymes, early peptide-metal complexes could have catalyzed energy transfer from the environment on the early Earth and enabled the evolution of modern metabolism

Keywords: hydrogenase, prebiotic enzyme, metalloenzyme, computational design

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Authors: Anusha Bhardwaj, Shekhar Shinde

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Nitric oxide (NO•) has been documented in research papers as one of the most versatile player in the therapeutics. It is identified as a biological multifunctional messenger molecule which is synthesized by the action of nitric oxide synthase (NOS) enzyme from L-arginine. The protective and the toxic effect in conjunction form the complete picture of the biological function of nitric oxide in humans. The dual nature is because of various factors such as concentration of NO, the isoform of NOS involved, type of cells in which it is synthesized, reaction partners like proteins, reactive oxygen intermediates, prosthetic groups, thiols etc., availability of the substrate L-arginine, intracellular environment in which NO is produced and generation of guanosine 3, 5’- cyclic monophosphate (cGMP). Activation of NOS through infection or trauma leads to one or more systemic effects including enhanced immune activity against invading pathogens, vaso/bronchodilatation in the cardiovascular and respiratory systems and altered neurotransmission which can be protective or toxic. Hence, NO affects the balance between healthy signaling and neurodegeneration in the brain. In lungs, it has beneficial effects on the function of airways as a bronchodilator and acts as the neurotransmitter of bronchodilator nerves. Whereas, on the other hand, NO may have deleterious effects by amplifying the asthmatic inflammatory response and also act as a vasodilator in the airways by increasing plasma exudation. But NOS Inhibitors and NO donors hamper the signalling pathway and hence a therapeutic application of NO is compromised.

Keywords: nitric oxide, multifunctional, dual nature, therapeutic applications

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Authors: Abdelgawad, Salah El-Tahawy

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This paper aimed to establish econometrical equation models for the Nile delta region in Egypt, which will represent a basement for future predictions of Lumpy skin disease outbreaks and its pathway in relation to climate change. Data of lumpy skin disease (LSD) outbreaks were collected from the cattle farms located in the provinces representing the Nile delta region during 1 January, 2015 to December, 2015. The obtained results indicated that there was a significant association between the degree of the LSD outbreaks and the investigated climate factors (temperature, wind speed, and humidity) and the outbreaks peaked during the months of June, July, and August and gradually decreased to the lowest rate in January, February, and December. The model obtained depicted that the increment of these climate factors were associated with evidently increment on LSD outbreaks on the Nile Delta of Egypt. The model validation process was done by the root mean square error (RMSE) and means bias (MB) which compared the number of LSD outbreaks expected with the number of observed outbreaks and estimated the confidence level of the model. The value of RMSE was 1.38% and MB was 99.50% confirming that this established model described the current association between the LSD outbreaks and the change on climate factors and also can be used as a base for predicting the of LSD outbreaks depending on the climatic change on the future.

Keywords: LSD, climate factors, Nile delta, modeling

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Authors: Anurag Kumar Pandey, Tapan Kumar Nath, Santanu Dhara

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Polluted water by industrial effluents or dyes has become a major global concern, particularly in developing countries. Such environmental contaminants constitute a serious threat to biodiversity, ecosystems, and human health worldwide; thus, their treatment is critical. The usage of nanoparticles has been discovered to be a potential water treatment method with high efficiency, cheap manufacturing costs, and green synthesis. Carbon dots have attracted the interest of researchers due to their unique properties, such as high water solubility, ease of production, great electron-donating ability, and low toxicity. In this context, we synthesized iodine-doped clove buds-derived carbon dots (I-CCDs) for the Fenton-like degradation of environmental contaminants in water (such as methylene blue (MB) and rhodamine-B (Rh-B) dye). The formation of I-CCDs has been confirmed using various spectroscopy techniques. I-CCDs have demonstrated remarkable optical, cytocompatibility, and antibacterial capabilities. The C-dots that were synthesized were found to be an effective catalyst for the reduction of MB and Rh-B utilizing NaBH4 as a reducing agent. UV-visible spectroscopy was used to construct a detailed pathway for dye reduction step by step. As-prepared I-CCDs have the potential to be a promising solution for wastewater purification and treatment systems.

Keywords: iodine-doped carbon dots, wastewater treatment and purification, environmental friendly, antibacterial

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Authors: K. Julia Rose Mary, Victor Arokia Doss

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Electrical and chemical stimulations up-regulate phosphorylaion of CREB, a transcriptional factor that induces its target gene production for memory consolidation and Late Long-Term Potentiation (L-LTP) in CA1 region of the hippocampus. L-LTP requires complex interactions among second-messenger signaling cascade molecules such as cAMP, CAMKII, CAMKIV, MAPK, RSK, PKA, all of which converge to phosphorylate CREB which along with CBP induces the transcription of target genes involved in memory consolidation. A differential equation based model for L-LTP representing stimulus-mediated activation of downstream mediators which confirms the steep, supralinear stimulus-response effects of activation and inhibition was used. The same was extended to accommodate the inhibitory effect of the Inducible cAMP Early Repressor (ICER). ICER is the natural inducible CREB antagonist represses CRE-Mediated gene transcription involved in long-term plasticity for learning and memory. After verifying the sensitivity and robustness of the model, we had simulated it with various empirical levels of repressor concentration to analyse their effect on the gene induction. The model appears to predict the regulatory dynamics of repression on the L-LTP and agrees with the experimental values. The flux data obtained in the simulations demonstrate various aspects of equilibrium between the gene induction and repression.

Keywords: CREB, L-LTP, mathematical modeling, simulation

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Authors: Thomas P. Jones

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Overview: Drowning is an important cause of accidental death, particularly in children and young people. Although many survive drowning incidents, it is a relatively rare presenting complaint in Emergency Departments. When cases do present, they can be complex and unpredictable. For patients to receive the best care, it is important that their management is standardized and evidence based, however this can be difficult in a topic area with limited studies and inconsistencies in case reporting. Objectives: To review recent cases to assess the performance of Manchester Royal Infirmary Emergency Department in the management of near drowning. To produce evidence based guideline on the management of drowning victims in the ED. Methods: Emergency department records were searched for patients with the diagnosis of ‘fatal drowning’ or ‘nearly drowning’ and two relevant case notes reviewed. To produce the guideline a literature review was conducted and a series of structured short cut systematic reviews known as Best BETs carried out. This information was used to produce a clear treatment pathway. Results: The case studies emphasized the variety in presentation of drowning victims whilst highlighting inconsistencies in management and documentation. An evidence-based guideline is presented as a flowchart, which illustrates the relevant investigations and treatment that victims of a drowning incident should receive, based on the best available evidence. Conclusion: It is hoped that when put into practice, the guideline will improve and standardize patient care in cases of near drowning. An audit is recommended to assess its effectiveness.

Keywords: drowning, near drowning, non fatal drowning, fatal drowning

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Authors: Lorena F. Axinte

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Territorial rescaling is a universal practice in the UK, following a logic of agglomeration and competition as the only chance for cities to thrive. Cardiff Capital Region is one of the latest examples, and its governance structures and developmental narratives are currently being shaped. Its evolution must be compatible with the Wellbeing of Future Generations Act, a Welsh legislation that requires public bodies to put sustainability at the core of all actions. Departing from this case study, the project follows the evolution of Cardiff Capital Region and assesses it based on a new a conceptual framework that connects the notions of regenerative development, collaborative governance, and progressive regionalism. The hypothetical synergies between these different theoretical perspectives are demonstrated, inferring that if regenerative development is aimed at, it must necessarily start with collaborative modes of governance. The objective is to explore (a) whether expanding the network of active stakeholders who get to intervene in the governance structure can contribute to a more progressive definition and development of the city region and (b) whether this can be considered a pathway towards regenerative development. The exploratory fieldwork conducted during the initial phase of the project used qualitative methods, which will be complemented next by different participatory research approaches, as well as a quantitative analysis. Despite being in its early days, the study is showing that a wider range of voices can indeed change priorities, reconcile and balance between the economic drivers and the wider social, economic, cultural and environmental aspects.

Keywords: Cardiff Capital Region, collaborative governance, progressive regionalism, regenerative development

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Authors: Swapna Guntupalli, Leela Madhuri Chalasani, Kshatri Jyothi, C. V. Rao, Bondili J. S.

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The study hypothesizes that enhanced biodegradation of Polycyclic Aromatic Hydrocarbons (PAHs) is achievable with an assemblage of microorganisms that are capable of producing biofilm and biosurfactants. Accordingly, PAHs degrading microorganism’s (bacteria, fungi, actinomycetes and yeast) were screened and grouped into different consortia based on their capabilities to produce biofilm and biosurfactants. Among these, Consortium BTSN09 consisting of bacterial fungal cocultures showed highest degradation due to the synergistic action between them. Degradation effiencies were evaluated using HPLC and GC-MS. Within 7days, BTSN09 showed 51% and 50.7% degradation of Phenanthrene (PHE) and Pyrene (PYR) with 200mg/L and 100 mg/L concentrations respectively in a liquid medium. In addition, several degradative enzymes like laccases, 1hydroxy-2-naphthoicacid dioxygenase, 2-carboxybenzaldehyde dehydrogenase, catechol1,2 dioxygenase and catechol2,3 dioxygenase activity was observed during degradation. Degradation metabolites were identified using GC-MS analysis and from the results it was confirmed that the metabolism of degradation proceeds via pthalic acid pathway for both PAHs. Besides, Microbial consortia also demonstrated good biosurfactant production capacity, achieving maximum oil displacement area and emulsification activity of 19.62 cm2, 65.5% in presence of PAHs as sole carbon source. Scanning Electron Microscopy analysis revealed exopolysaccharides (EPS) production, micro and macrocolonies formation with different stages of biofim development in presence of PAHs during degradation.

Keywords: PAHs, biosurfactant, biofilm, biodegradation

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