Search results for: cooperative signaling

Authors: Gunasekaran Raja, Ramkumar Jayaraman

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In this paper, we consider CCL-N (Cooperative Cross Layer Network) topology based on the cross layer (both centralized and distributed) environment to form network communities. Various performance metrics related to the IEEE 802.16 networks are discussed to design CCL-N Topology. In CCL-N topology, nodes are classified as master nodes (Master Base Station [MBS]) and serving nodes (Relay Station [RS]). Nodes communities are organized based on the networking terminologies. Based on CCL-N Topology, various simulation analyses for both transparent and non-transparent relays are tabulated and throughput efficiency is calculated. Weighted load balancing problem plays a challenging role in IEEE 802.16 network. CoTS (Concurrent Transmission Scheduling) Scheme is formulated in terms of three aspects – transmission mechanism based on identical communities, different communities and identical node communities. CoTS scheme helps in identifying the weighted load balancing problem. Based on the analytical results, modularity value is inversely proportional to that of the error value. The modularity value plays a key role in solving the CoTS problem based on hop count. The transmission mechanism for identical node community has no impact since modularity value is same for all the network groups. In this paper three aspects of communities based on the modularity value which helps in solving the problem of weighted load balancing and CoTS are discussed.

Keywords: cross layer network topology, concurrent scheduling, modularity value, network communities and weighted load balancing

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Authors: Tamar Arieli

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Cross-border cooperation has long been hailed as a means for stabilizing and normalizing relations between former enemies. Cooperation in problem-solving and realizing of local interests in post-conflict environments can indeed serve as a basis for developing dialogue and meaningful relations between neighbors across borders. Hence the potential for formerly sealed borders to serve as a basis for generating local and national perceptions of interdependence and as a buffer against the resume of conflict. Central questions which arise for policy-makers and third parties are how to facilitate cross-border cooperation and which areas of cooperation best serve to normalize post-conflict border regions. The Israel-Jordan border functions as a post-conflict border, in that it is a peaceful border since the 1994 Israel-Jordan peace treaty yet cross-border relations are defined but the highly securitized nature of the border region and the ongoing Arab-Israel regional conflict. This case study is based on long term qualitative research carried out in the border regions of both Israel and Jordan, which mapped and analyzed cross-border in a wide range of activities – social interactions sponsored by peace-facilitating NGOs, government sponsored agricultural cooperation, municipal initiated emergency planning in cross-border continuous urban settings, private cross-border business ventures and various environmental cooperative initiatives. These cooperative initiatives are evaluated through multiple interviews carried out with initiators and partners in cross-border cooperation as well as analysis of documentation, funding and media. These cooperative interactions are compared based on levels of cross-border local and official awareness and involvement as well as sustainability over time. This research identifies environmental cooperation as the most sustainable area of cross- border cooperation and as most conducive to generating perceptions of regional interdependence. This is a variation to the ‘New Middle East’ vision of business-based cooperation leading to conflict amelioration and regional stability. Environmental cooperation serving the public good rather than personal profit enjoys social legitimization even in the face of widespread anti-normalization sentiments common in the post-conflict environment. This insight is examined in light of philosophical and social aspects of the natural environment and its social perceptions. This research has theoretical implications for better understanding dynamics of cooperation and conflict, as well as practical ramifications for practitioners in border region policy and management.

Keywords: borders, cooperation, post-conflict, security

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Authors: Simona Moravcova, Jiri Novotny, Zdenka Bendova

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The pineal gland of the vertebrate brain is a circumventricular organ which serves as a major neuroendocrine gland with the primary function of rhythmic secretion of neurohormone melatonin under the control of the hypothalamic suprachiasmatic nucleus (SCN). Soon after the onset of the darkness, the activity of the key rate-limiting enzyme for melatonin synthesis, arylalkylamine N-acetyltransferase (AANAT), raises due to the increased release of norepinephrine from sympathetic neurons terminating on the parenchymal cells where it binds to β-adrenergic receptors. Melatonin codes the length of the night, and it is well recognized for its anti-inflammatory effects. However, to our knowledge, less is known about the effect of the immune system on the melatonin biosynthesis and the precise role of the STAT3 in the signaling pathway leading to the expression of AANAT. Lipopolysaccharide (LPS) is the essential component in the outer surface membrane of gram-negative bacteria and acts as a strong stimulator of natural and innate immunity. STAT3 acts as an important factor in immune response. Here we investigated the effect of LPS on the components of the melatonergic synthetic pathway in the pineal gland. The experiments were performed both in vivo and in vitro. The changes in AANAT activity were determined by radioenzymatic assay. PCR analyses were carried out to detect aa-nat, icer, spi-3 and stat3 gene expression. From our results, it is apparent that the high basal level of phosphorylated forms of STAT3 can be elevated after systemic as well as in vitro administration of LPS. Our experiments have shown that LPS reduces melatonin synthesis, nevertheless, the activity of AANAT was increased. Moreover, the basal level of phosphorylated STAT3 counteracts β-adrenergic receptor-mediated aa-nat gene expression and sustains its own and spi-3 gene expression. In conclusion, LPS can affect immunomodulators such as melatonin in the pineal gland.

Keywords: AANAT, lipopolysaccharide, pineal gland, rat, STAT3

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Authors: Odey Moses Ogah, Felix Terhemba Ikyereve

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The study was carried out to analyzed risks in financing agriculture by agricultural cooperatives in Benue State, Nigeria. The study made use of research questionnaires for data collection. A multistage sampling technique was used to select a sample of 210 respondents from 21 agricultural cooperatives. Both descriptive and inferential statistics were employed in data analysis. Loan defaulting (66.7%) and reduction in savings by members (51.4%) were the major causes of risks faced by agricultural cooperatives in financing agriculture in the study area. Other causes include adverse changes in commodity prices (48.6%), disaster (45.7%), among others. It was found that risks adversely influence the profitability and competition of agricultural cooperatives (82.9%). Multiple regression analysis results showed that the coefficient of multiple determinations was 0.67, implying that the explanatory variables included in the model accounted for 67% of the variation in the level of profitability of agricultural cooperatives. The number of loans, average amount of loan and the interest rate were significant and important determinants of profitability of the cooperatives. The majority of the respondents (88.6%) made use of loan guarantors as a strategy of managing loan default/no repayment. It was found that the majority (70%) of the respondents were faced with the challenge of lack of insurance cover. The study recommends that agricultural cooperative officials should be encouraged to undergo formal training and education to easily acquire administrative skills in the management of agricultural loans; Farmer's loan size should be increased and released on time to enable them to use it effectively. Policies that enhance insuring farm activities should be put in place to discourage farmers from risk aversion.

Keywords: agriculture, analysis, cooperative, finance, risks

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Authors: Paras Gupta, Rohit Goyal, Yamini Chauhan, Pyare Lal Sharma

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Background: Bombax ceiba Linn., commonly called as Semal, is used in various gastro-intestinal disturbances. It contains lupeol which inhibits PTP-1B, adipogenesis, TG synthesis and accumulation of lipids in adipocytes and adipokines whereas the flavonoids isolated from B. ceiba has FAS inhibitory activity. The present study was aimed to investigate ameliorative potential of Bombax ceiba to experimental obesity in Wistar rats, and its possible mechanism of action. Methods: Male Wistar albino rats weighing 180–220 g were employed in present study. Experimental obesity was induced by feeding high fat diet for 10 weeks. Methanolic extract of B. ceiba extract 100, 200 and 400 mg/kg and Gemfibrozil 50 mg/kg as standard drug were given orally from 7th to 10th week. Results: Induction with HFD for 10 weeks caused significant (p < 0.05) increase in % body wt, BMI, LEE indices; serum glucose, triglyceride, LDL, VLDL, cholesterol, free fatty acid, ALT, AST; tissue TBARS, nitrate/nitrite levels; different fat pads and relative liver weight; and significant decrease in food intake (g and kcal), serum HDL and tissue glutathione levels in HFD control rats. Treatment with B. ceiba extract and Gemfibrozil significantly attenuated these HFD induced changes, as compared to HFD control. The effect of B. ceiba 200 and 400 mg/kg was more pronounced in comparison to Gemfibrozil. Conclusion: On the basis of results obtained, it may be concluded that the methanolic extract of stem bark of Bombax ceiba has significant ameliorative potential against HFD induced obesity in rats, possibly through modulation of FAS and PTP-1B signaling due to the presence of flavonoids and lupeol.

Keywords: obesity, Bombax ceiba, free fatty acid, protein tyrosine phosphatase-1B, fatty acid synthase

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Authors: Khalil Aryanfar, Shahrzad Sanjari, Elmira Hafez, Pariya Gholipor

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The aim of this study was to Evaluate and compare the male and female students’ life skills of theoretical, technical-vocational and Job and Knowledge branches of secondary high school period. The research method is descriptive - survey Research population was 5892 students from three high schools in Tehran, sample size was determined 342 patients according to Morgan’s table and by stratified random sampling. The data collection tool was a questionnaire designed by the researchers that the reliability was more than 85/0 respectively. Data was anglicized by Kryskal Wallis and Mann-Whitney U-test. In three branches of theoretical, technical-vocational and Job and Knowledge The variables of academic achievement, the importance of organization, problem solving, seeking knowledge, good habits, mental and physical self-concept, family orientation and future orientation was not significant differences, in the variables of cooperative behavior, and ready for change was but significant differences. Variables such as academic achievement, seek knowledge, good habits, mental and physical, seeking direction to future cooperative behavior between boys and girls with the confidence of at least 95/0 and the variable ready for change among boys and girls by ensuring 0932 / There was an However, the importance of variables, problem solving, self-concept and family orientation was not significantly different.

Keywords: life skills, high school, theoretical, technical-vocational, job and knowledge

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Authors: Marawan Abd Elbaset Mohamed, Hanan A. Ogaly, Rehab F. Abdel-Rahman, Ahmed-Farid O.A., Marwa S. Khattab, Reham M. Abd-Elsalam

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Liver fibrosis is a severe worldwide health concern due to various chronic liver disorders. Hepatic encephalopathy (HE) is one of its most common complications affecting liver and brain cognitive function. Beta-Carotene (B-Car) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. The study attempted to know B-Car neuroprotective potential against thioacetamide (TAA)-induced neurotoxicity and cognitive decline in HE in rats. Hepatic encephalopathy was induced by TAA (100 mg/kg, i.p.) three times per week for two weeks. B-Car was given orally (10 or 20 mg/kg) daily for two weeks after TAA injections. Organ body weight ratio, Serum transaminase activities, liver’s antioxidant parameters, ammonia, and liver histopathology were assessed. Also, the brain’s mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), antioxidant parameters, adenosine triphosphate (ATP), adenosine monophosphate (AMP), norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) cAMP response element-binding protein (CREB) expression and B-cell lymphoma 2 (Bcl-2) expression were measured. The brain’s cognitive functions (Spontaneous locomotor activity, Rotarod performance test, Object recognition test) were assessed. B-Car prevented alteration of the brain’s cognitive function in a dose-dependent manner. The histopathological outcomes supported these biochemical evidences. Based on these results, it could be established that B-Car could be assigned to treat the brain’s neurotoxicity consequences of HE via downregualtion of MAPK/NF-κB signaling pathways.

Keywords: beta-carotene, liver injury, MAPK, NF-κB, rat, thioacetamide

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Authors: N. Umasuthan, S. D. N. K. Bathige, W. S. Thulasitha, I. Whang, J. Lee

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The MyD88 is an evolutionarily conserved host-expressed adaptor protein that is essential for proper TLR/ IL1R immune-response signaling. A previously identified complete cDNA (1626 bp) of OfMyD88 comprised an ORF of 867 bp encoding a protein of 288 amino acids (32.9 kDa). The gDNA (3761 bp) of OfMyD88 revealed a quinquepartite genome organization composed of 5 exons (with the sizes of 310, 132, 178, 92 and 155 bp) separated by 4 introns. All the introns displayed splice signals consistent with the consensus GT/AG rule. A bipartite domain structure with two domains namely death domain (24-103) coded by 1st exon, and TIR domain (151-288) coded by last 3 exons were identified through in silico analysis. Moreover, homology modeling of these two domains revealed a similar quaternary folding nature between human and rock bream homologs. A comprehensive comparison of vertebrate MyD88 genes showed that they possess a 5-exonic structure. In this structure, the last three exons were strongly conserved, and this suggests that a rigid structure has been maintained during vertebrate evolution. A cluster of TATA box-like sequences were found 0.25 kb upstream of cDNA starting position. In addition, putative 5'-flanking region of OfMyD88 was predicted to have TFBS implicated with TLR signaling, including copies of NFB1, APRF/ STAT3, Sp1, IRF1 and 2 and Stat1/2. Using qPCR technique, a ubiquitous mRNA expression was detected in liver and blood. Furthermore, a significantly up-regulated transcriptional expression of OfMyD88 was detected in head kidney (12-24 h; >2-fold), spleen (6 h; 1.5-fold), liver (3 h; 1.9-fold) and intestine (24 h; ~2-fold) post-Fla challenge. These data suggest a crucial role for MyD88 in antibacterial immunity of teleosts.

Keywords: MyD88, innate immunity, flagellin, genomic analysis

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Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

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Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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Authors: Kakali Bhadra

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Binding of small molecules to DNA and recently to RNA, continues to attract considerable attention for developing effective therapeutic agents for control of gene expression. This work focuses towards understanding interaction of harmalol, a dihydro beta-carboline alkaloid, with different nucleic acid motifs viz. double stranded CT DNA, single stranded A-form poly(A), double-stranded A-form of poly(C)·poly(G) and clover leaf tRNAphe by different spectroscopic, calorimetric and molecular modeling techniques. Results of this study converge to suggest that (i) binding constant varied in the order of CT DNA > poly(C)·poly(G) > tRNAphe > poly(A), (ii) non-cooperative binding of harmalol to poly(C)·poly(G) and poly(A) and cooperative binding with CT DNA and tRNAphe, (iii) significant structural changes of CT DNA, poly(C)·poly(G) and tRNAphe with concomitant induction of optical activity in the bound achiral alkaloid molecules, while with poly(A) no intrinsic CD perturbation was observed, (iv) the binding was predominantly exothermic, enthalpy driven, entropy favoured with CT DNA and poly(C)·poly(G) while it was entropy driven with tRNAphe and poly(A), (v) a hydrophobic contribution and comparatively large role of non-polyelectrolytic forces to Gibbs energy changes with CT DNA, poly(C)·poly(G) and tRNAphe, and (vi) intercalated state of harmalol with CT DNA and poly(C)·poly(G) structure as revealed from molecular docking and supported by the viscometric data. Furthermore, with competition dialysis assay it was shown that harmalol prefers hetero GC sequences. All these findings unequivocally pointed out that harmalol prefers binding with ds CT DNA followed by ds poly(C)·poly(G), clover leaf tRNAphe and least with ss poly(A). The results highlight the importance of structural elements in these natural beta-carboline alkaloids in stabilizing different DNA and RNA of various motifs for developing nucleic acid based better therapeutic agents.

Keywords: calorimetry, docking, DNA/RNA-alkaloid interaction, harmalol, spectroscopy

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Authors: Iman Shabanzadeh

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The economic growth and the special model of development in China have caused sensitivity in the public opinion of the world regarding the nature of this growth and development. In this regard, the Chinese have tried to put an end to such alarming procedures by using all the tools at their disposal and seek to present a peaceful and cooperative image of themselves. In this way, one of the most important diplomatic tools that Beijing has used to reduce the concerns caused by the Threat Theory has been the use of soft power resources and its tools in its development policies. This article begins by analyzing the concept of soft power and examining its foundations in international relations, and continues to examine the components of soft power in its Chinese version. The main purpose of the article is to figure out about the position of West Asia in China's soft power strategy and resources China use to achieve its goals in this region. In response to the main question, the paper's hypothesis is that soft power in its Chinese version had significant differences from Joseph Nye's original idea. In fact, the Chinese have imported the American version of soft power and adjusted, strengthened and, in other words, internalized it with their abilities, capacities and political philosophy. Based on this, China's software presence in West Asia can be traced in three areas. The first source of China's soft power in this region of West Asia is cultural in nature and is realized through strategies such as "use of educational tools and methods", "media methods" and "tourism industry". The second source is related to political soft power, which is applied through the policy of "balance of influence" and the policy of "mediation" and relying on the "ideological foundations of Confucianism". The third source also refers to China's economic soft power and is realized through three tools: "energy exchanges", "foreign investments" and "Belt-Road initiative". The research method of this article is descriptive-analytical.

Keywords: soft power, cooperative power, china, west asia

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Authors: Hadjer Messabih

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The M’zab architecture has preserved its identity that was able to endure for centuries conserving practically the same way of life and the same building techniques since the 11th century. Even more, the newly built ksar Tafilelt is also designed to meet the local tradition. In 1996, a community led project was initiated to build a “new ksar” named Tafilelt based on a traditional form of community-led cooperative housing. It is a unique experience in the field of community housing that reproduces traditional architectural patterns while addressing contemporary ways of life with their expected modern comfort. This research is based on the hypothesis that the process of producing ksar Tafilelt is culturally responsive to a conservative community that was characterized by certain values which were transmitted to this ksar manifesting as cultural continuity. It aims at investigating what type of cultural continuity manifests itself in the co-production of ksar Tafilelt and the way the settlement and its houses are produced and inhabited, as well as the new emerging values and adaptive transition in social relations. The research methodology is based on a combination of questionnaires, in depth interviews, photography, and site visit to record and demonstrate how these buildings respond to peoples’ needs. Post Occupancy Evaluation (POE) is also employed in order to understand the lessons that can be learned from this project. Finally, this study proves that the cultural continuity that was transmitted from the Ibadi community is sill manifested in ksar Tafilelt, which provided strong religious bonds and a strong sense of community. The research findings have resulted in a number of lessons and principles that can be learnt from the project of ksar Tafilelt which can inform future practices of housing provision and design in Algeria and other countries.

Keywords: community-led cooperative housing, conservative community, cultural continuity, post occupancy evaluation

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Authors: Hossein Bazmara, Kaamran Raahemifar, Mostafa Sefidgar, Madjid Soltani

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Angiogenesis is formation of new blood vessels from existing vessels. Due to flow of blood in vessels, during angiogenesis, blood flow plays an important role in regulating the angiogenesis process. Multiple mathematical models of angiogenesis have been proposed to simulate the formation of the complicated network of capillaries around a tumor. In this work, a multi-scale model of angiogenesis is developed to show the effect of blood flow on capillaries and network formation. This model spans multiple temporal and spatial scales, i.e. intracellular (molecular), cellular, and extracellular (tissue) scales. In intracellular or molecular scale, the signaling cascade of endothelial cells is obtained. Two main stages in development of a vessel are considered. In the first stage, single sprouts are extended toward the tumor. In this stage, the main regulator of endothelial cells behavior is the signals from extracellular matrix. After anastomosis and formation of closed loops, blood flow starts in the capillaries. In this stage, blood flow induced signals regulate endothelial cells behaviors. In cellular scale, growth and migration of endothelial cells is modeled with a discrete lattice Monte Carlo method called cellular Pott's model (CPM). In extracellular (tissue) scale, diffusion of tumor angiogenic factors in the extracellular matrix, formation of closed loops (anastomosis), and shear stress induced by blood flow is considered. The model is able to simulate the formation of a closed loop and its extension. The results are validated against experimental data. The results show that, without blood flow, the capillaries are not able to maintain their integrity.

Keywords: angiogenesis, endothelial cells, multi-scale model, cellular Pott's model, signaling cascade

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Authors: ZhenlinJu, Christopher P. Vellano, RehanAkbani, Yiling Lu, Gordon B. Mills

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The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal characteristics, such as profound disruption of cell-cell junctions, loss of apical-basolateral polarity, and extensive reorganization of the actin cytoskeleton to induce cell motility and invasion. A hallmark of EMT is its capacity to promote metastasis, which is due in part to activation of several transcription factors and subsequent downregulation of E-cadherin. Unfortunately, current approaches have yet to uncover robust protein marker sets that can classify tumors as possessing strong EMT signatures. In this study, we utilize reverse phase protein array (RPPA) data and consensus clustering methods to successfully classify a subset of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tumors into an EMT protein signaling group (EMT group). The overall survival (OS) of patients in the EMT group is significantly worse than those in the other Hormone and PI3K/AKT signaling groups. In addition to a shrinkage and selection method for linear regression (LASSO), we applied training/test set and Monte Carlo resampling approaches to identify a set of protein markers that predicts the EMT status of CESC tumors. We fit a logistic model to these protein markers and developed a classifier, which was fixed in the training set and validated in the testing set. The classifier robustly predicted the EMT status of the testing set with an area under the curve (AUC) of 0.975 by Receiver Operating Characteristic (ROC) analysis. This method not only identifies a core set of proteins underlying an EMT signature in cervical cancer patients, but also provides a tool to examine protein predictors that drive molecular subtypes in other diseases.

Keywords: consensus clustering, TCGA CESC, Silhouette, Monte Carlo LASSO

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Authors: Dieudonne Mevono Mvogo

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The Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES)-Intergovernmental Panel on Climate Change (IPCC) co-sponsored workshop report suggests that climate change and biodiversity loss are two of the most pressing issues of the Anthropocene. Research establishes the interconnection between climate change and biodiversity. On the one hand, the impact of climate change on biodiversity loss – 14 % over the past century – is projected to surpass other threats – land and sea use 34 % and direct exploitation of species 23 % – during the 21st century. Response measures to climate change also affect biodiversity negatively or positively. On the other hand, actions to halt or reverse biodiversity loss can enhance land and ocean capacity for carbon sequestration. These actions can also promote adaptation by ensuring adaptive capacity. This systemic interaction between climate change and biodiversity affects the human quality of life. The United Nations Secretariat's report entitled 'Gaps in international environmental law and environment-related instruments: towards a global pact for the environment,' released in 2018, states that cooperation and mutual support among agreements dealing with climate change, the protection of the marine environment, freshwater resources and hazardous waste are indispensable for the effective implementation of the Convention on the Biological Diversity (CBD). Since biodiversity is being lost at an alarming rate, this study aims to evaluate the cooperative framework for the coherence and coordination between climate change and biodiversity regimes to provide co-benefits for climate and biodiversity crises. It questions the potential improvement regarding integrating ecosystem-based approaches and nature-based solutions – promoted by the CBD – into the United Nations Framework Convention on Climate Change (UNFCCC).

Keywords: rio conventions, climate change, biodiversity, cooperative framework, ecosystem-based approaches, nature-based solutions

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Authors: Ana Mafalda Silva, Rebeca Fontes, Ana Paula Vaz, Carla Carreira, Ana Corte-Real

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Decades of research on the topic of interpersonal violence against minors highlight five main conclusions: 1) it causes harmful effects on children's development and health; 2) it is prevalent; 3) it violates children's rights; 4) it can be prevented and 5) parents are the main aggressors. The child abuse scenario is identified through clinical observation, administrative data and self-reports. The most used instruments are self-reports; however, there are no valid and reliable self-report instruments for minors, which consist of a retrospective interpretation of the situation by the victim already in her adult phase and/or by her parents. Clinical observation and collection of information, namely from the orofacial region, are essential in the early identification of these situations. The management of medical data, such as personal data, must comply with the General Data Protection Regulation (GDPR), in Europe, and with the General Law of Data Protection (LGPD), in Brazil. This review aims to answer the question: In a situation of medical assistance to minors, in the suspicion of interpersonal violence, due to mistreatment, is it necessary for the guardians to provide consent in the registration and sharing of personal data, namely medical ones. A scoping review was carried out based on a search by the Web of Science and Pubmed search engines. Four papers and two documents from the grey literature were selected. As found, the process of identifying and signaling child abuse by the health professional, and the necessary early intervention in defense of the minor as a victim of abuse, comply with the guidelines expressed in the GDPR and LGPD. This way, the notification in maltreatment scenarios by health professionals should be a priority and there shouldn’t be the fear or anxiety of legal repercussions that stands in the way of collecting and treating the data necessary for the signaling procedure that safeguards and promotes the welfare of children living with abuse.

Keywords: child abuse, disease notifications, ethics, healthcare assistance

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Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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Authors: Nicholas C. Rose, Christopher D. Spicer

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The regeneration of damaged or diseased tissues would provide an invaluable therapeutic tool in biological research and medicine. Cells must be provided with a number of different biochemical signals in order to form mature tissue through complex signaling networks that are difficult to recreate in synthetic materials. The ability to attach and detach bioactive proteins from material in an iterative and dynamic manner would therefore present a powerful way to mimic natural biochemical signaling cascades for tissue growth. We propose to reversibly attach these bioactive proteins using ortho-boronoimine (oBI) linkages and related derivatives formed by the reaction of an ortho-boronobenzaldehyde with a nucleophilic amine derivative. To enable the use of oBIs for biomaterial modification, we have studied binding and cleavage processes with precise detail in the context of small molecule models. A panel of oBI complexes has been synthesized and screened using a novel Förster resonance energy transfer (FRET) assay, using a cyanine dye FRET pair (Cy3 and Cy5), to identify the most reactive boron-aldehyde/amine nucleophile pairs. Upon conjugation of the dyes, FRET occurs under Cy3 excitation and the resultant ratio of Cy3:Cy5 emission directly correlates to conversion. Reaction kinetics and equilibria can be accurately quantified for reactive pairs, with dissociation constants of oBI derivatives in water (KD) found to span 9-orders of magnitude (10⁻²-10⁻¹¹ M). These studies have provided us with a better understanding of oBI linkages that we hope to exploit to reversibly attach bioconjugates to materials. The long-term aim of the project is to develop a modular biomaterial platform that can be used to help combat chronic diseases such as osteoarthritis, heart disease, and chronic wounds by providing cells with potent biological stimuli for tissue engineering.

Keywords: dynamic, bioconjugation, bornoimine, rapid, physiological

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Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

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Authors: Michael K. O. Ayomoh, Oyindamola A. Omotuyi

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Autonomous mobile robots deployed to explore or operate in a never explored or an abandoned sub-surface mine requires extreme effectiveness in coordination and communication. In a bid to transmit information from the depth of the mine to the external surface in real-time and amidst diverse physical, chemical and virtual impediments, the concept of unified cooperative robots is seen to be a proficient approach. This paper presents an effective [human → robot → task] coordination framework for effective exploration of an abandoned underground mine. The problem addressed in this research is basically the development of a globalized optimization model premised on time series differentiation and geometrical configurations for effective positioning of the two classes of robots in the cooperation namely the outermost stationary master (OSM) robots and the innermost dynamic task (IDT) robots for effective bi-directional signal transmission. In addition, the synchronization of a vision system and wireless communication system for both categories of robots, fiber optics system for the OSM robots in cases of highly sloppy or vertical mine channels and an autonomous battery recharging capability for the IDT robots further enhanced the proposed concept. The OSM robots are the master robots which are positioned at strategic locations starting from the mine open surface down to its base using a fiber-optic cable or a wireless communication medium all subject to the identified mine geometrical configuration. The OSM robots are usually stationary and function by coordinating the transmission of signals from the IDT robots at the base of the mine to the surface and in a reverse order based on human decisions at the surface control station. The proposed scheme also presents an optimized number of robots required to form the cooperation in a bid to reduce overall operational cost and system complexity.

Keywords: sub-surface mine, wireless communication, outermost stationary master robots, inner-most dynamic robots, fiber optic

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Authors: Mohit Wadhawan, Sushma Rathaur

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Lymphatic filariasis, also called elephantiasis is a tropical disease afflicting over 120 million people in 81 countries worldwide. Existing anti filarial drugs are effective against the larval stages of filarial parasites which call for an urgent need of drugs which are macrofilaricidal. Identification of molecular targets crucial for survival of filarial parasites is a prerequisite for drug designing. Prolyl oligopeptidase (POP) is one such crucial enzyme involved in the maturation and degradation of neuropeptides and peptide hormones. We have identified this peptidase in the bovine filarial parasite, Setaria cervi. Effect of inhibition of POP on the proteome profile of filarial parasite has been discussed in this study. Filarial parasites were exposed to Z-pro-prolinal (ZPP), a specific POP inhibitor for 8 h and the motility and viability of the parasites was observed. It significantly reduced the motility and viability of the parasites. To study the proteome profile, the cytosolic, endoplasmic reticulum (ER) and mitochondrial extracts of the adult female parasites were subjected to 2-dimensional electrophoresis. As analyzed by the PD-Quest software, the ZPP caused the alteration in the different subcellular proteins, and the significantly altered proteins were identified using MALDI-MS/MS spectrometry. The major proteins identified were found to play important role in diverse biological functions like signaling, redox regulation, energy metabolism, stress response, and cytoskeleton formation. Moreover, we found upregulation in the calcium binding proteins such as calreticulin, calponin, and calpain-6 suggesting that POP inhibition regulates calcium release. This relates to earlier reports that POP plays non-catalytic role in inositol 1,4,5-trisphosphate (IP3) signaling inducing release of calcium from ER. Taken together, the data demonstrated that inhibition of prolyl oligopeptidase alter the overall proteome signifying its role in survival of the filarial parasites. Thus this study provides a basis for the use of POP as a chemotherapeutic target for the treatment of lymphatic filariasis.

Keywords: lymphatic filariasis, setaria cervi, prolyl oligopeptidase, proteomics

Procedia PDF Downloads 258

Authors: S. Ben-Shabat, T. Turgeman, O. Leubinski, N. Roth-Bejerano, V. Kagan-Zur, Y. Sitrit

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The ectomycorrhizal (ECM) desert truffle Terfezia boudieri produces edible fruit bodies and forms symbiosis with its host plant Helianthemum sessiliflorum (Cistaceae) in the Negev desert of Israel. The symbiosis is vital for both partners' survival under desert conditions. Under desert habitat conditions, ECMs must form symbiosis before entering the dry season. To secure a successful encounter, in the course of evolution, both partners have responded by evolving special signals exchange that facilitates recognition. Members of the Cistaceae family serve as host plants for many important truffles. Conceivably, during evolution a common molecule present in Cistaceae plants was recruited to facilitate successful encounter with ectomycorrhizas. Arbuscular vesicular fungi (AM) are promiscuous in host preferences, in contrast, ECM fungi show specificity to host plants. Accordingly, we hypothesize that H. sessiliflorum secretes a chemotrophic-signaling, which is common to plants hosting ECM fungi belonging to the Pezizales. However, thus far no signaling molecules have been identified in ECM fungi. We developed a bioassay for chemotrophic activity. Fractionation of root exudates revealed a substance with chemotrophic activity and molecular mass of 534. Following the above concept, screening the transcriptome of Terfezia, grown under chemoattraction, discovered genes showing high homology to G proteins-coupled receptors of plant pathogens involved in positive chemotaxis and chemotaxis suppression. This study aimed to identify the active molecule using analytical methods (LC-MS, NMR etc.). This should contribute to our understanding of how ECM fungi communicate with their hosts in the rhizosphere. In line with the ability of Terfezia to form also endomycorrhizal symbiosis like AM fungi, analysis of the mechanisms may likewise be applicable to AM fungi. Developing methods to manipulate fungal growth by the chemoattractant can open new ways to improve inoculation of plants.

Keywords: chemotrophic signal, Helianthemum sessiliflorum, Terfezia boudieri, ECM

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Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi

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Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.

Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration

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Authors: Niyongabo Elyse

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Prefabricated building construction is a pioneering approach that combines design, production, and assembly to attain energy efficiency, environmental sustainability, and economic feasibility. Despite continuous development in the industry in China, the low technical maturity of standardized design, factory production, and construction assembly introduces uncertainties affecting prefabricated component production and on-site assembly processes. This research focuses on enhancing project management performance under uncertainty to help enterprises navigate these challenges and optimize project resources. The study introduces a perspective on how uncertain factors influence the implementation of prefabricated building construction projects. It proposes a theoretical model considering project process management ability, adaptability to uncertain environments, and collaboration ability of project participants. The impact of uncertain factors is demonstrated through case studies and quantitative analysis, revealing constraints on implementation time, cost, quality, and safety. To address uncertainties in prefabricated component production scheduling, a fuzzy model is presented, expressing processing times in interval values. The model utilizes a cooperative co-evolution evolution algorithm (CCEA) to optimize scheduling, demonstrated through a real case study showcasing reduced project duration and minimized effects of processing time disturbances. Additionally, the research addresses on-site assembly construction scheduling, considering the relationship between task processing times and assigned resources. A multi-objective model with fuzzy activity durations is proposed, employing a hybrid cooperative co-evolution evolution algorithm (HCCEA) to optimize project scheduling. Results from real case studies indicate improved project performance in terms of duration, cost, and resilience to processing time delays and resource changes. The study also introduces a multistage dynamic process control model, utilizing IoT technology for real-time monitoring during component production and construction assembly. This approach dynamically adjusts schedules when constraints arise, leading to enhanced project management performance, as demonstrated in a real prefabricated housing project. Key contributions include a fuzzy prefabricated components production scheduling model, a multi-objective multi-mode resource-constrained construction project scheduling model with fuzzy activity durations, a multi-stage dynamic process control model, and a cooperative co-evolution evolution algorithm. The integrated mathematical model addresses the complexity of prefabricated building construction project management, providing a theoretical foundation for practical decision-making in the field.

Keywords: prefabricated construction, project management performance, uncertainty, fuzzy scheduling

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Authors: Tarana Siddika, Ilka U. Heinemann, Patrick O’Donoghue

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Protein kinase B (AKT1) is a serine/threonine kinase and central transducer of cell survival pathways. Typical approaches to study AKT1 biology in cells rely on growth factor or insulin stimulation that activates AKT1 via phosphorylation at two key regulatory sites (Threonine308, Serine473), yet cell stimulation also activates many other kinases and fails to differentiate the effect of the two main activating sites of AKT1 on downstream substrate phosphorylation and cell growth. While both AKT1 activating sites are associated with disease and used as clinical markers, in some cancers, high levels of Threonine308 phosphorylation are associated with poor prognosis while in others poor survival correlates with high Serine473 levels. To produce cells with specific AKT1 activity, a system was developed to deliver active AKT1 to human cells. AKT1 phospho-variants were produced from Escherichia coli with programmed phosphorylation by genetic code expansion. Tagging of AKT1 with an N-terminal cell penetrating peptide tag derived from the human immunodeficiency virus trans-activator of transcription (TAT) helped to enter AKT1 proteins in mammalian cells. The TAT-tag did not alter AKT1 kinase activity and was necessary and sufficient to rapidly deliver AKT1 protein variants that persisted in human cells for 24 h without the need to use transfection reagents. TAT-pAKT1T308, TAT-pAKT1S473 and TAT-pAKT1T308S473 proteins induced selective phosphorylation of the known AKT1 substrate GSK-3αβ, and downstream stimulation of the AKT1 pathway as evidenced by phosphorylation of ribosomal protein S6 at Serine240/244 in transfected cells. Increase in cell growth and proliferation was observed due to the transfection of different phosphorylated AKT1 protein variants compared to cells with TAT-AKT1 protein. The data demonstrate efficient delivery of AKT1 with programmed phosphorylation to human cells, thus establishing a cell-based model system to investigate signaling that is dependent on specific AKT1 activity and phosphorylation.

Keywords: cell penetrating peptide, cell signaling, protein kinase b (AKT1), phosphorylation

Procedia PDF Downloads 83

Authors: Mohammad M. Aria, Fatma Öz, Yashar Esmaeilian, Marco Carofiglio, Valentina Cauda, Özlem Yalçın

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Photoelectrical stimulation of cells with semiconductor organic polymers have been shown promising applications in neuroprosthetics such as retinal prosthesis. Photoelectrical stimulation of the cell membranes can be induced through a photo-electric charge separation mechanism in the semiconductor materials, and it can alter intracellular calcium level through both stimulation of voltage-gated ion channels and increase of intracellular reactive oxygen species (ROS) level. On the other hand, targeting voltage-gated ion channels in cancer cells to induce cell apoptosis through calcium signaling alternation is an effective mechanism which has been explained before. In this regard, remote control of the voltage-gated ion channels aimed to alter intracellular calcium by using photo-active organic polymers can be novel technology in cancer therapy. In this study, we used P (ITO/Indium thin oxide)/P3HT(poly(3-hexylthiophene-2,5-diyl)) and PN (ITO/ZnO/P3HT) photovoltaic junctions to stimulate MDA-MB-231 breast cancer cells. We showed that the photo-stimulation of breast cancer cells through photo capacitive current generated by the photovoltaic junctions are able to excite the cells and alternate intracellular calcium based on the calcium imaging (at 8mW/cm² green light intensity and 10-50 ms light durations), which has been reported already to safety stimulate neurons. The control group did not undergo light treatment and was cultured in T-75 flasks. We detected 20-30% cell death for ITO/P3HT and 51-60% cell death for ITO/ZnO/P3HT samples in the light treated MDA-MB-231 cell group. Western blot analysis demonstrated poly(ADP-ribose) polymerase (PARP) activated cell death in the light treated group. Furthermore, Annexin V and PI fluorescent staining indicated both apoptosis and necrosis in treated cells. In conclusion, our findings revealed that the photoelectrical stimulation of cells (through long time overstimulation) can induce cell death in cancer cells.

Keywords: Ca²⁺ signaling, cancer therapy, electrically excitable cells, photoelectrical stimulation, voltage-gated ion channels

Procedia PDF Downloads 148

Authors: Akanksha Agrawal, Richa Rathor, Geetha Suryakumar

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Muscle represents about ¾ of the body mass, and a healthy muscular system is required for human performance. A healthy muscular system is dynamically balanced via the catabolic and anabolic process. High altitude associated hypoxia altered this redox balance via producing reactive oxygen and nitrogen species that ultimately modulates protein structure and function, hence, disrupts proteostasis or protein homeostasis. The mechanism by which proteostasis is clinched includes regulated protein translation, protein folding, and protein degradation machinery. Perturbation in any of these mechanisms could increase proteome imbalance in the cellular processes. Altered proteostasis in skeletal muscle is likely to be responsible for contributing muscular atrophy in response to hypoxia. Therefore, we planned to elucidate the mechanism involving altered proteostasis leading to skeletal muscle atrophy under chronic hypobaric hypoxia. Material and Methods-Male Sprague Dawley rats weighing about 200-220 were divided into five groups - Control (Normoxic animals), 1d, 3d, 7d and 14d hypobaric hypoxia exposed animals. The animals were exposed to simulated hypoxia equivalent to 282 torr pressure (equivalent to an altitude of 7620m, 8% oxygen) at 25°C. On completion of chronic hypobaric hypoxia (CHH) exposure, rats were sacrificed, muscle was excised and biochemical, histopathological and protein synthesis signaling were studied. Results-A number of changes were observed with the CHH exposure time period. ROS was increased significantly on 07 and 14 days which were attributed to protein oxidation via damaging muscle protein structure by oxidation of amino acids moiety. The oxidative damage to the protein further enhanced the various protein degradation pathways. Calcium activated cysteine proteases and other intracellular proteases participate in protein turnover in muscles. Therefore, we analysed calpain and 20S proteosome activity which were noticeably increased at CHH exposure as compared to control group representing enhanced muscle protein catabolism. Since inflammatory markers (myokines) affect protein synthesis and triggers degradation machinery. So, we determined inflammatory pathway regulated under hypoxic environment. Other striking finding of the study was upregulation of Akt/PKB translational machinery that was increased on CHH exposure. Akt, p-Akt, p70 S6kinase, and GSK- 3β expression were upregulated till 7d of CHH exposure. Apoptosis related markers, caspase-3, caspase-9 and annexin V was also increased on CHH exposure. Conclusion: The present study provides evidence of disrupted proteostasis under chronic hypobaric hypoxia. A profound loss of muscle mass is accompanied by the muscle damage leading to apoptosis and cell death under CHH. These cellular stress response pathways may play a pivotal role in hypobaric hypoxia induced skeletal muscle atrophy. Further research in these signaling pathways will lead to development of therapeutic interventions for amelioration of hypoxia induced muscle atrophy.

Keywords: Akt/PKB translational machinery, chronic hypobaric hypoxia, muscle atrophy, protein degradation

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Authors: Li-Wei Wu, Chung-Yu Wang

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Recently, interest has been generated in the search for a new reference framework for value creation that is centered on the co-creation process. Co-creation implies cooperative value creation between service firms and customers and requires the building of experiences as well as the resolution of problems through the combined effort of the parties in the relationship. For customers, values are always co-created through their participation in services. Customers can ultimately determine the value of the service in use. This new approach emphasizes that a customer’s participation in the service process is considered indispensable to value co-creation. An important feature of service in the context of exchange is co-production, which implies that a certain amount of participation is needed from customers to co-produce a service and hence co-create value. Co-production no doubt helps customers better understand and take charge of their own roles in the service process. Thus, this proposal is to encourage co-production, thus facilitating value co-creation of that is reflected in both customers and service firms. Four determinants of co-production are identified in this study, namely, commitment, trust, asset specificity, and decision-making uncertainty. Commitment is an essential dimension that directly results in successful cooperative behaviors. Trust helps establish a relational environment that is fundamental to cross-border cooperation. Asset specificity motivates co-production because this determinant may enhance return on asset investment. Decision-making uncertainty prompts customers to collaborate with service firms in making decisions. In other words, customers adjust their roles and are increasingly engaged in co-production when commitment, trust, asset specificity, and decision-making uncertainty are enhanced. Although studies have examined the preceding effects, to our best knowledge, none has empirically examined the simultaneous effects of all the curvilinear relationships in a single study. When these determinants are excessive, however, customers will not engage in co-production process. In brief, we suggest that the relationships of commitment, trust, asset specificity, and decision-making uncertainty with co-production are curvilinear or are inverse U-shaped. These new forms of curvilinear relationships have not been identified in existing literature on co-production; therefore, they complement extant linear approaches. Most importantly, we aim to consider both the bright and the dark sides of the determinants of co-production.

Keywords: co-production, commitment, trust, asset specificity, decision-making uncertainty

Procedia PDF Downloads 167

Authors: Olga Hernán-Vega, Patricia López-Rodríguez, David Escot-Bocanegra, Raúl Fernández-Recio, Ignacio Bravo

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Non-Cooperative Target Identification has become a key research domain in the Defense industry since it provides the ability to recognize targets at long distance and under any weather condition. High Resolution Range Profiles, one-dimensional radar images where the reflectivity of a target is projected onto the radar line of sight, are widely used for identification of flying targets. According to that, to face this problem, an approach to Non-Cooperative Target Identification based on the exploitation of Singular Value Decomposition to a matrix of range profiles is presented. Target Identification based on one-dimensional radar images compares a collection of profiles of a given target, namely test set, with the profiles included in a pre-loaded database, namely training set. The classification is improved by using Singular Value Decomposition since it allows to model each aircraft as a subspace and to accomplish recognition in a transformed domain where the main features are easier to extract hence, reducing unwanted information such as noise. Singular Value Decomposition permits to define a signal subspace which contain the highest percentage of the energy, and a noise subspace which will be discarded. This way, only the valuable information of each target is used in the recognition process. The identification algorithm is based on finding the target that minimizes the angle between subspaces and takes place in a transformed domain. Two metrics, F1 and F2, based on Singular Value Decomposition are accomplished in the identification process. In the case of F2, the angle is weighted, since the top vectors set the importance in the contribution to the formation of a target signal, on the contrary F1 simply shows the evolution of the unweighted angle. In order to have a wide database or radar signatures and evaluate the performance, range profiles are obtained through numerical simulation of seven civil aircraft at defined trajectories taken from an actual measurement. Taking into account the nature of the datasets, the main drawback of using simulated profiles instead of actual measured profiles is that the former implies an ideal identification scenario, since measured profiles suffer from noise, clutter and other unwanted information and simulated profiles don't. In this case, the test and training samples have similar nature and usually a similar high signal-to-noise ratio, so as to assess the feasibility of the approach, the addition of noise has been considered before the creation of the test set. The identification results applying the unweighted and weighted metrics are analysed for demonstrating which algorithm provides the best robustness against noise in an actual possible scenario. So as to confirm the validity of the methodology, identification experiments of profiles coming from electromagnetic simulations are conducted, revealing promising results. Considering the dissimilarities between the test and training sets when noise is added, the recognition performance has been improved when weighting is applied. Future experiments with larger sets are expected to be conducted with the aim of finally using actual profiles as test sets in a real hostile situation.

Keywords: HRRP, NCTI, simulated/synthetic database, SVD

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Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

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Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

Procedia PDF Downloads 97