Search results for: glioma invasion

Authors: Mohamed Faslan

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This research examines the impact of the politicization of the fishing dispute on India-Sri Lanka relations, particularly the influence of internal and party politics. The maritime border is clearly demarcated between India and Sri Lanka. India and Sri Lanka signed bilateral agreements on maritime boundaries in 1974 and 1976 respectively. They signed the United Nations Law of the Sea- III as well. Despite this, fishing disputes persist between the two nations. Tamil Nadu politics is closely linked with Sri Lankan Tamil issues and Tamil Nadu has been playing a significant role in Indo-Lanka relations. This is due to the fact that many Indian trawlers involved in fishing activities in Sri Lankan waters are from Tamil Nadu. The Government of Tamil Nadu is also very concerned about the issue of fishing in Sri Lankan waters. During the ethnic war, Sri Lankan fishermen were restricted on fishing activities in the Northern sea by the Sri Lankan Government and Liberation Tigers of Tamil Elam (LTTE). This created a vacuum in the Northern sea of Sri Lanka, and Indian trawlers filled the vacuum with the support of the LTTE. After the end of the war, Northern fishermen of Sri Lanka recommenced their fishing activities and realized that the Tamil Nadu trawlers had scooped their fishing resources. The Northern fishermen started to protest the invasion of Indian trawlers and pushed the Sri Lankan Government to stop the Indian trawlers. When Sri Lanka arrested Indian fishermen and confiscated their fishing boats, the Tamil Nadu Government used this as an opportunity to accuse Sri Lanka as having a Sinhalese government, to express feelings of hatred towards Sri Lanka due to the ethnic war against Tamils and tried to increase the voting bank by selling Tamil feelings. Thus, this research finds that Tamil Nadu does not associate this fishing dispute with Tamils in Sri Lanka but with the Sinhalese despite the status quo. This research has covered the Northern fishermen and stakeholders of Sri Lanka and could not do any field research in India due to visa restrictions. However, the researcher tries to balance the gap by referring to secondary sources and a few interviews with Indian scholars.

Keywords: Indo Lanka relations, fishing dispute, maritime border, Tamil Nadu & Sri Lankan waters

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Authors: Andrew Kanzunguze, Sopani Sichinga, Paston Simkoko, George Nxumayo, Cosmas, V. B. Dambo

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Early detection of plant invasions is a necessary prerequisite for effective invasive plant management in protected areas. This study was conducted to determine the distribution and abundance of alien invasive trees in Nyika National Park (NNP). Data on species' presence and abundance were collected from belt transects (n=31) in a 100 square kilometer area on the central plateau. The data were tested for normality using the Shapiro-Wilk test; Mann-Whitney test was carried out to compare frequencies and abundances between the species, and geographical information systems were used for spatial analyses. Results revealed that Black Wattle (Acacia mearnsii), Mexican Pine (Pinus patula) and Himalayan Raspberry (Rubus ellipticus) were the main alien invasive trees on the plateau. A. mearnsii was localized in the areas where it was first introduced, whereas P. patula and R. ellipticus were spread out beyond original points of introduction. R. ellipticus occurred as dense, extensive (up to 50 meters) thickets on the margins of forest patches and pine stands, whilst P. patula trees were frequent in the valleys, occurring most densely (up to 39 stems per 100 square meters) south-west of Chelinda camp on the central plateau with high variation in tree heights. Additionally, there were no significant differences in abundance between R. ellipticus (48) and P. patula (48) in the study area (p > 0.05) It was concluded that R. ellipticus and P. patula require more attention as compared to A. mearnsii. Howbeit, further studies into the invasion ecology of both P. patula and R. ellipticus on the Nyika plateau are highly recommended so as to assess the threat posed by the species on biodiversity, and recommend appropriate conservation measures in the national park.

Keywords: alien-invasive trees, Himalayan raspberry, Nyika National Park, Mexican pine

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Authors: Gloria Patricia Manurung

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Jakarta Bus Rapid Transit (BRT) system which was established in 2009 to reduce private vehicle usage and ease the rush hour gridlock throughout the Jakarta Greater area, has failed to achieve its purpose. With gradually increasing the number of private vehicles ownership and reduced road space by the BRT lane construction, private vehicle users intuitively invade the exclusive lane of BRT, creating local traffic along the BRT network. Invaded BRT lanes costs become the same with the road network, making BRT which is supposed to be the main public transportation in the city becoming unreliable. Efforts to guard critical lanes with preventing the invasion by allocating traffic agents at several intersections have been expended, lead to the improving congestion level along the lane. Given a set of number of traffic agents, this study uses an analytical approach to finding the best deployment strategy of traffic agent on a simplified Jakarta road network in minimizing the BRT link cost which is expected to lead to the improvement of BRT system time reliability. User-equilibrium model of traffic assignment is used to reproduce the origin-destination demand flow on the network and the optimum solution conventionally can be obtained with brute force algorithm. This method’s main constraint is that traffic assignment simulation time escalates exponentially with the increase of set of agent’s number and network size. Our proposed metaheuristic and heuristic algorithms perform linear simulation time increase and result in minimized BRT cost approaching to brute force algorithm optimization. Further analysis of the overall network link cost should be performed to see the impact of traffic agent deployment to the network system.

Keywords: traffic assignment, user equilibrium, greedy algorithm, optimization

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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: M. Borgie, Z. Dagher, F. Ledoux, A. Verdin, F. Cazier, H. Greige, P. Shirali, D. Courcot

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In October 2013, the International Agency for Research on Cancer (IARC) classified outdoor air pollution and fine particulate matter (PM2.5) as carcinogenic to humans. Despite the clearly relationship established by epidemiological studies between PM exposure and the onset of respiratory and cardiovascular diseases, uncertainties remain about the physiopathological mechanisms responsible for these diseases. The aim of this work was to evaluate the toxicological effects of two samples of atmospheric PM2.5 collected at urban and rural sites on human bronchial epithelial cells, BEAS-2B, especially to investigate the metabolic activation of organic compounds, the alteration of epigenetic mechanisms (i.e. microRNAs genes expression), the phosphorylation of H2AX and the telomerase activity. Our results showed a significant increase in CYP1A1, CYP1B1, and AhRR genes expression, miR-21 gene expression, H2AX phosphorylation and telomerase activity in BEAS-2B cells after their exposure to PM2.5, both in a dose and site-dependent manner. These results showed that PM2.5, especially urban PM, are able to induce the expression of metabolizing enzymes which can provide metabolic biotransformation of organic compounds into more toxic and carcinogenic metabolites, and to induce the expression of the oncomiR miR-21 which promotes cell growth and enhances tumor invasion and metastasis in lung cancer. In addition, our results have highlighted the role of PM2.5 in the activation of telomerase, which can maintain the telomeres length and subsequently preventing cell death, and have also demonstrated the ability of PM2.5 to induce DNA breaks and thus to increase the risk of mutations or chromosomal translocations that lead to genomic instability. All these factors may contribute to cell abnormalities, and thus the development of cancer.

Keywords: BEAS-2B cells, carcinogenesis, epigenetic alterations and genotoxicity, PM2.5

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Authors: Mohammed Sghir Taleb

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Introduction The date palm (Phoenix dactylifera L.) represents an essential element of the oasis ecosystem for Saharan and pre-Saharan regions of Morocco. It plays an important role, not only due to its economic importance, but also its ecological adaptation to, firstly, to ensure necessary protection for crops against underlying warm and dry sales, and secondly to contribute to the fight against desertification. This is one of the oldest cultivated plant species best adapted to difficult climatic conditions of the Saharan and pre-Saharan regions, because of its ecological requirements and economically most suitable for investing in oasis agriculture. Methodology The methodology is mainly based on a literature review of principal theses and projects for the conservation of flora and vegetation. Results The date palm has multiple uses. Indeed, it produces fruits rich in nutrients, provides a multitude of secondary products and generates needed revenue for the survival of oasis populations. In Morocco, the development and modernization of the date palm sector face, both upstream and downstream of the industry, several major constraints. In addition to climate constraints (prolonged drought), in its environment (lack of water resources), to the incessant invasion of disease Bayoud, Moroccan palm ecosystem suffers from a low level of technical and traditional practices prevail and traditional, from the choice of variety and site preparation up to harvesting and recycling of products. Conclusion The date palm plays an important role in the socioeconomic development of local and national level. However, this ecosystem however, is subject to numerous degradation factors caused by anthropogenic action and climate change. to reverse the trends, several programs have been developed by Morocco for the restoration of degraded areas and the development of the Phoenix dactylifera ecosystem to meet the needs of local populations and the development of the national economy.

Keywords: efforts, flora, ecosystem, forest, conservation, Morocco

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

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Authors: Ali A. Bazzi, Ameer Hamza, Riley O’Hara, Kimberly Kado, Karen H. Hagglund, Lamia Fathallah, Robert T. Morris

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Introduction: Endometrial Cancer is a common gynecologic malignancy primarily treated with complete surgical staging, which may include complete pelvic and para-aortic lymphadenectomy. The role of lymphadenectomy is controversial, especially the intraoperative indications for the procedure. Three factors are important in decision to proceed with lymphadenectomy: Myometrial invasion, maximum tumor dimension, and histology. Many institutions incorporate these criteria in varying degrees in the decision to proceed with lymphadenectomy. This investigation assesses the use of intraoperatively measured MTD with and without pre-operative histologic grade. Methods: This study compared retrospectively EEC patients with intraoperatively measured MTD ≤2 cm to those with MTD >2 cm from January 1, 2002 to August 31, 2017. This assessment compared those with MTD ≤ 2cm with endometrial biopsy (EB) grade 1-2 to patients with MTD > 2cm with EB grade 3. Lymph node metastasis (LNM), recurrence, and survival were compared in these groups. Results: This study reviewed 222 patient cases. In tumors > 2 cm, LNM occurred in 20% cases while in tumors ≤ 2 cm, LNM was found in 6% cases (p=0.04). Recurrence and mean survival based on last follow up visit in these two groups were not statistically different (p=0.78 and 0.36 respectively). Data demonstrated a trend that when combined with preoperative EB International Federation of Gynecology and Obstetrics (FIGO) grade, a higher proportion of patients with EB FIGO Grade 3 and MTD > 2 cm had LNM compared to those with EB FIGO Grade 1-2 and MTD ≤ 2 cm (43% vs, 11%, p=0.06). LNM was found in 15% of cases in which lymphadenectomy was performed based on current practices, whereas if the criteria of EB FIGO 3 and MTD > 2 cm were used the incidence of LNM would have been 44% cases. However, using this criterion, two patients would not have had their nodal metastases detected. Compared to the current practice, the sensitivity and specificity of the proposed criteria would be 60% and 81%, respectively. The PPV and NPV would be 43% and 90%, respectively. Conclusion: The results indicate that MTD combined with EB FIGO grade can detect LNM in a higher proportion of cases when compared to current practice. MTD combined with EB FIGO grade may eliminate the need of frozen section sampling in a substantial number of cases.

Keywords: endometrial cancer, FIGO grade, lymphadenectomy, tumor size

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Authors: Cristine P. Canlas, Crislene Mae L. Gever, Patricia Bea R. Rosialda, Ma. Nina Regina M. Quibod, Perry Archival C. Buenavente, Normandy M. Barbecho, Cynthia Adeline A. Layusa, Michael Day

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Invasive plants have an impact on global biodiversity and ecosystem function, and their management is a complex and formidable task. Two of these invasive plant species, Lantana camara and Chromolaena odorata, are found in the Philippines. Lantana camara has the ability to suppress the growth of and outcompete neighboring plants. Chromolaena odorata causes serious agricultural and economical damage and causes fire hazards during dry season. In addition, both species has been reported to poison livestock. One of the known global management strategies to control invasive plants is the introduction of biological control agents. These natural enemies of the invasive plants reduce population density and impacts of the invasive plants, resulting in the balance of the nature in their invasion. Through secondary data sources, interviews, and field validation (e.g. microhabitat searches, sweep netting, opportunistic sampling, photo-documentation), we investigated whether the biocontrol agents previously released by the Philippine Coconut Authority (PCA) in their Davao Research Center to control these invasive plants are still present and are affecting their respective host weeds. We confirm the presence of the biocontrol agent of L. camara, Uroplata girardi, which was introduced in 1985, and Cecidochares connexa, a biocontrol agent of C. odorata released in 2003. Four other biocontrol agents were found to affect L. camara. Signs of damage (e.g. stem galls in C. odorata, and leaf mines in L. camara) signify that these biocontrol agents have successfully established outside of their release site in Davao. Further investigating the extent of the spread of these biocontrol agents in the Philippines and their damage to the two weeds will contribute to the management of invasive plant species in the country.

Keywords: invasive alien species, biological control agent, entomology, worst weeds

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Authors: Marie Fouet, Olivier Maire, Cécile Masse, Hugues Blanchet, Salomé Coignard, Nicolas Lavesque, Guillaume Bernard

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Exacerbated by global change, extreme climatic events such as atmospheric and marine heat waves may interact with the spread of non-indigenous species and their associated impacts on marine ecosystems. Since the 1970’s, the introduction of non-indigenous species due to oyster exchanges has been numerous. Among them, the Asian date mussel Arcuatula senhousia has colonized a large number of ecosystems worldwide (e.g., California, New Zealand, Italy). In these places, A.senhousia led to important habitat modifications in the benthic compartment through physical, biological, and biogeochemical effects associated with the development of dense mussel populations. In Arcachon Bay (France), a coastal lagoon of the French Atlantic and hotspot of oyster farming, abundances of A. senhousia recently increased, following a lag time of ca. 20 years since the first record of the species in 2002. Here, we addressed the potential effects of the interaction between A. senhousia invasion and heatwave intensity on ecosystem functioning within an intertidal mudflat. More precisely, two realistic intensities (“High” and “Severe”) of combined marine and atmospheric heatwaves have been simulated in an experimental tidal mesocosm system onto which naturally varying densities of A. senhousia and associated benthic communities were exposed in sediment cores collected in situ. Following a six-day exposure, community-scale responses were assessed by measuring benthic metabolism (oxygen and nutrient fluxes) in each core. Results show that besides significantly enhanced benthic metabolism with increasing heatwave intensity, mussel density clearly mediated the magnitude of the community-scale response, thereby highlighting the importance of understanding the interactive effects of environmental stressors co-occurring with non-indigenous species and their dependencies for a better assessment of their impacts.

Keywords: arcuatula senhousia, benthic habitat, ecosystem functioning, heatwaves, metabolism

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Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim

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Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.

Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species

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Authors: Petra Borilova Linhartova, Michaela Ruckova, Sabina Sevcikova, Natalie Mlcuchova, Jan Bohm, Katerina Zukalova, Monika Vlachova, Jiri Dolina, Lumir Kunovsky, Radek Kroupa, Zdenek Pavlovsky, Zdenek Danek, Tereza Deissova, Lydie Izakovicova Holla, Ondrej Slaby, Zdenek Kala

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Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. Specific microRNAs (miRNAs), small non-coding RNAs that function as posttranscriptional regulators of gene expression, were repeatedly proved to play key roles in the pathogenesis of these diseases. This pilot study aimed to analyze four selected miRNAs in esophageal tissues from healthy controls (HC) and patients with reflux esophagitis (RE)/BE/EAC, as well as to compare expression at the site of Barrett's mucosa/adenocarcinoma and healthy esophageal tissue outside the area of the main pathology in patients with BE/EAC. In this pilot study, 22 individuals (3 HC, 8 RE, 5 BE, 6 EAC) were included and endoscopically examined. RNA was isolated from the fresh-frozen esophageal tissue (stored in the RNAlater™ Stabilization Solution −70°C) using the AllPrep DNA/RNA/miRNA Universal Kit. Subsequent RT-qPCR analysis was performed using selected TaqMan MicroRNA Assays for miR-21, miR-34a, miR-196a, miR-196b, and endogenous control (RNU44). While the expression of miR-21 in the esophageal tissue with the main pathology was decreased in BE and EAC patients in comparison to the group of HC and RE patients (p=0.01), the expression of miR-196a was increased in the BE and EAC patients (p<0.01). Correlations between those miRNAs expression in tissue and severity of diagnosis were observed (p<0.05). In addition, miR-196a was significantly more expressed at the site with the main pathology than in paired adjacent esophageal tissue in BE and EAC patients (p<0.01). In conclusion, our pilot results showed that miR-196a, which regulates the proliferation, invasion, and migration (and was previously associated with esophageal squamous cell carcinoma and marked as a potential therapeutic target), could be a diagnostic tissue biomarker for BE and EAC as well.

Keywords: microRNA, barrett´s esophagus, esophageal adenocarcinoma, biomarker

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Authors: Sara S. Fouad, Omneya Messallam

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In 1818, a seventy-five kilometer long canal was dug (called the Mahmoudiyah canal) connecting between Alexandria city in Egypt and the western branch of the Nile. It was a productive resource and vital to its environment, context, transportation, and recreation. It played a significant role in people’s lives and Alexandria city’s shape. The canal, which was the main vein of goods’ transporting from Alexandria’s seaport to the different parts of Egypt, was still in use today as a major source of clear water in the city. But nowadays, Mahmoudiyah canal is converting into ‘dead waterway’. The canal became sources of pollution as a result of solid and industrial waste thus causing many diseases, destroying communities and biodiversity, with urban invasion, the loss of community aesthetic value and healthy environment. Therefore, this paper aims to propose an urban strategy, as a solution to revive the forgotten canal, through recreating a cultural promenade on its shore. The main aim of this research is to formulate decent quality of life, unpolluted space, an area gathering the city space for nature, tourism and investments. As a case study, this paper investigates Mahmoudiyah canal through urban and ecological analyses, aiming to design an urban strategy for reviving it by creating a cultural promenade enriched with public spaces and green areas, which can most probably enhance the quality of life, city re-living and development. Community participation is also considered as vital and intrinsic implementation stage. The empirical research involved using several data assembly methods such as interviews, mental mapping, structural observations and questionnaires. The paper ends with a set of conclusions leading to proposals for the Mahmoudiyah canal revitalization considering the complex challenges and processes of sustainable regeneration focusing on city’s rehabilitation and lost identity.

Keywords: Mahmoudiyah canal, community aesthetic value, city re-living, cultural promenade

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Authors: Ali Liaghat, Navid Tavanpour, Nima Tavanpour

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An increase in population and prevalence of urbanity have led plan makers and decision makers put effort into sustainable development of cities at national and local levels. One of the important issues in urban development is compliance with safety issues in cities. Despite natural disasters and unexpected events such as floods, earthquakes, hurricanes, fires, etc., urban development should be regarded as an axiom, or else any form of construction and development is not safe, because it will greatly harm economic growth and development and pose an obstacle to achieving sustainable development, plus a loss to lives and finances of people. Therefore, in line with urban development, it is necessary to identify particular environmental and local issues as determinants and pay attention to them at the top of everything, in that we can call it a good action and factor in urban sustainable developments. Physical structure of each city represents how it has developed or its development shaped and what incidents, changes, natural disasters it has undergone over time. Since any form of development plan should be in accordance with the previous situations of cities, disregarding it, unfortunately, can escalate into uncontrolled urban development, non-resistant and unstable construction against earthquake or invasion of river areas, destruction of agricultural lands or vegetation, periodic floods over time. It has been viewed as serious threats to developing cities, and typically caused destruction of bed and other urban facilities as well as damages to lives and finances. In addition, uncontrolled development has caused cities to look ugly in terms of urban façade, and off and on such unplanned measures caused the country to face countless losses, and it not only vitiates expenses incurred, but it will also impose additional costs of reconstruction, i.e. it is unsustainable development. Thus, in this paper, in addition to a discussion about necessity for a profound attitude toward this subject and making long-term plans, programs for organizing river and its surrounding area, creating open and green urban spaces, retrofitting and flood preventing are presented for sustainable safety and development of cities along with a critique of successful countries.

Keywords: flood, sustainable development, urbanisation, urban management

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Authors: Nuran Öze

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People always want to be aware of what is happening around them. The nature of man constantly triggers the need for gathering information because of curiosity. The media has emerged to save people the need for information. It is known that the media has changed with the technological developments over time, diversified and, people's information needs are provided in different ways. Today, the Internet has become an integral part of everyday life. The invasion of the Internet into everyday life practices at this level affects every aspect of life. These effects cause people to change their life practices. Technological developments have always influenced of people, the way they reach information. Looking at the history of the media, the breaking point about the dissemination of information is seen as the invention of the machine of the printing press. This adventure that started with written media has now become a multi-dimensional structure. Written, audio, visual media has now changed shape with new technologies. Especially emerging of the internet to everyday life, of course, has effects on media field. 'New media' has appeared which contains most of traditional media features in its'. While in the one hand this transformation enables captures a harmony between traditional and new media, on the other hand, new media and traditional media are rivaling each other. The purpose of this study is to examine the problematic relationship between traditional media and new media through the news reading practices of individuals. This study can be evaluated as a kind of media sociology. To reach this aim, two different field researches will be done besides literature review. The research will be conducted in Northern Cyprus. Northern Cyprus Northern Cyprus is located in the Mediterranean Sea. North Cyprus is a country which is not recognized by any country except Turkey. Despite this, takes its share from all technological developments take place in the world. One of the field researches will consist of the questionnaires to be applied on media readers' news reading practices. This survey will be conducted in a social media environment. The second field survey will be conducted in the form of interviews with general editorials or news directors in traditional media. In the second field survey, in-depth interview method will be applied. As a result of these investigations, supporting sides between the new media and the traditional media and directions which contrast with each other will be revealed. In addition to that, it will try to understand the attitudes and perceptions of readers about the traditional media and the new media in this study.

Keywords: new media, news, North Cyprus, traditional media

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Authors: Ayat Ayman Abdelaziz Ibrahim Amayem, Hassan Abdel-Salam, Zeyad El-Sayad

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Nowadays, ICTs have spread extensively in everyday life in an unprecedented way. A great attention is paid to the ICTs while ignoring the social aspect. With the immersive invasion of internet as well as smart phones’ applications and digital social networking, people become more socially connected through virtual spaces instead of meeting in physical public spaces. Thus, this paper aims to find the ways of implementing ICTs in public spaces to regain their status as attractive places for people, incite meetings in real life and create sustainable lively city centers. One selected example of urban space in the city center of Alexandria is selected for the study. Alexandria represents a large metropolitan city subjected to rapid transformation. Improving the quality of its public spaces will have great effects on the whole well-being of the city. The major roles that ICTs can play in the public space are: culture and art, education, planning and design, games and entertainment, and information and communication. Based on this classification various examples and proposals of ICTs interventions in public spaces are presented and analyzed to encourage good old fashioned social interaction by creating the New Social Public Place of this Digital Era. The paper will adopt methods such as questionnaire for evaluating the people’s willingness to accept the idea of using ICTs in public spaces, their needs and their proposals for an attractive place; the technique of observation to understand the people behavior and their movement through the space and finally will present an experimental design proposal for the selected urban space. Accordingly, this study will help to find design principles that can be adopted in the design of future public spaces to meet the needs of the digital era’s users with the new concepts of social life respecting the rules of place-making.

Keywords: Alexandria sustainable city center, digital place-making, ICTs, social interaction, social networking, urban places

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Authors: Asma Zaib, Saeed Khan, Ayaz Ahmed Noonari, Sehrish Bint-e-Mohsin

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Breast cancer is the most common cancer among females worldwide and is estimated that more than 450,000 deaths are reported each year. It accounts for about 14% of all female cancer deaths. Angiogenesis plays an essential role in Breast cancer development, invasion, and metastasis. Breast cancer predominantly begins in luminal epithelial cells lining the normal breast ducts. Breast carcinoma likely requires coordinated efforts of both increased proliferation and increased motility to progress to metastatic stages.Resveratrol: a natural stilbenoid, has anti-inflammatory and anticancer effects that inhibits proliferation of variety of human cancer cell lines, including breast, prostate, stomach, colon, pancreatic, and thyroid cancers.The objective of this study is:To investigate anti-neoangiogenesis effects of Resveratrol in breast cancer and to analyze inhibitory effects of resveratrol on aromatase, Erα, HER2/neu, and VEGFR.Docking is the computational determination of binding affinity between molecule (protein structure and ligand).We performed molecular docking using Swiss-Dock and to determine docking effects of (1) Resveratrol with Aromatase, (2) Resveratrol with ERα (3) Resveratrol with HER2/neu and (4) Resveratrol with VEGFR2.Docking results of resveratrol determined inhibitory effects on aromatase with binding energy of -7.28 kcal/mol which shows anticancerous effects on estrogen dependent breast tumors. Resveratrol also show inhibitory effects on ERα and HER2/new with binging energy -8.02, and -6.74 respectively; which revealed anti-cytoproliferative effects upon breast cancer. On the other hand resveratrol v/s VEGFR showed potential inhibitory effects on neo-angiogenesis with binding energy -7.68 kcal/mol, angiogenesis is the important phenomenon that promote tumor development and metastasis. Resveratrol is an anti-breast cancer agent conformed by in silico studies, it has been identified that resveratrol can inhibit breast cancer cells proliferation by acting as competitive inhibitor of aromatase, ERα and HER2 neo, while neo-angiogemesis is restricted by binding to VEGFR which authenticates the anti-carcinogenic effects of resveratrol against breast cancer.

Keywords: angiogenesis, anti-cytoproliferative, molecular docking, resveratrol

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Authors: Jonathan Josephs-Spaulding, Hannah Rettig, Simon Graspeunter, Jan Rupp, Christoph Kaleta

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Background: Recurrent urinary tract infections (rUTIs) are a global cause of emergency room visits and represent a significant burden for public health systems. Therefore, metatranscriptomic approaches to investigate metabolic exchange and crosstalk between uropathogenic Escherichia coli (UPEC), which is responsible for 90% of UTIs, and collaborating pathogens of the urogenital microbiome is necessary to better understand the pathogenetic processes underlying rUTIs. Objectives: This study aims to determine the level in which uropathogens optimize the host urinary metabolic environment to succeed during invasion. By developing patient-specific metabolic models of infection, these observations can be taken advantage of for the precision treatment of human disease. Methods: To date, we have set up an rUTI patient cohort and observed various urine-associated pathogens. From this cohort, we developed patient-specific metabolic models to predict bladder microbiome metabolism during rUTIs. This was done by creating an in silico metabolomic urine environment, which is representative of human urine. Metabolic models of uptake and cross-feeding of rUTI pathogens were created from genomes in relation to the artificial urine environment. Finally, microbial interactions were constrained by metatranscriptomics to indicate patient-specific metabolic requirements of pathogenic communities. Results: Metabolite uptake and cross-feeding are essential for strain growth; therefore, we plan to design patient-specific treatments by adjusting urinary metabolites through nutritional regimens to counteract uropathogens by depleting essential growth metabolites. These methods will provide mechanistic insights into the metabolic components of rUTI pathogenesis to provide an evidence-based tool for infection treatment.

Keywords: recurrent urinary tract infections, human microbiome, uropathogenic Escherichia coli, UPEC, microbial ecology

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Authors: Domenico Carmelo Mongelli, Laura Carnieletto, Michele De Carli, Filippo Busato

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Starting from the current context in which the Russian invasion in Ukraine has highlighted Europe's dependence on natural gas imports for heating buildings, this study proposes solutions to resolve this dependency and evaluates related scenarios in the near future. In the first part of this work the methodologies and results of the economic impact are indicated by simulating a massive replacement of boilers powered by fossil fuels with electrically powered hightemperature air-water heat pumps for heating residential buildings in different European climates, without changing the current energy mix. For each individual European region, the costs for the purchase and installation of heat pumps for all residential buildings have been determined. Again for each individual European region, the economic savings during the operation phase that would be obtained in this future scenario of energy transition from fossil fuels to the electrification of domestic heating were calculated. For the European regions for which the economic savings were identified as positive, the payback times of the economic investments were analysed. In the second part of the work, hypothesizing different scenarios for a possible greater use of renewable energy sources and therefore with different possible future scenarios of the energy mix, the methodologies and results of the simulations on the economic analysis and on the environmental analysis are reported which have allowed us to evaluate the future effects of the energy transition from boilers to heat pumps for each European region. In the third part, assuming a rapid short-term diffusion of cooling for European residential buildings, the penetration shares in the cooling market and future projections of energy needs for cooling for each European region have been identified. A database was created where the results of this research relating to 38 European Nations divided into 179 regions were reported. Other previous works on the topics covered were limited to analyzing individual European nations, without ever going into detail about the individual regions within each nation, while the original contribution of the present work lies in the fact that the results achieved allow a specific numerical analysis and punctual for every single European region.

Keywords: buildings, energy, Europe, future

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Authors: Shazia Shamim, Pallavi Gautam

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The present study describes the presence of rare or endangered plants from Poonch Dist., which spread over 1674 Km sq. located between latitude 330 25' N to 340 01' N and longitude 730 58' E to 740 35' E forming a part of the Northwest Himalaya in Jammu and Kashmir state of India, with the aim of suggesting the strategy for the conservation and promotion of cultivation of rare and endangered medicinal plants, as well as developing traditional knowledge of medicinal plants. The main threats to biodiversity and ecosystem are overexploitation, global climate change, habitat loss, fragmentation, pollution, and invasion of alien species and disturbance of community structure. Surveys were carried out during 2015-2016 throughout the Poonch valley. During the field survey, various criteria of International Union for the conservation of nature for categorizing threatened plants, extent of occurrence, area of occupancy, probability of extinction, etc. were measured. The rarity of species was determined by field study, visual estimations, and literature. During the collection, it was observed that few rare and endangered species which were present in the study area, are also mentioned in the prescribed red data book of Indian plants, International Union for conservation of nature, list of threatened species and list of Botanical Survey of India presented by its Northern Regional Centre. The study was based on extensive surveys of the study area and then concluded by preparing a list of plant species occurring in different seasons, the photographs of all these plant species were collected. Actual threats to the population of a selected plant species in a given area were recorded by direct observation. The present paper provides information about 22 rare and endangered medicinal plant species belonging to 18 families that are used by the native of these areas. Information provided includes botanical name, family name, local name, habitat, part used, ethno medicinal uses and brief preparation of the reported plant species is presented in the present work.

Keywords: biodiversity, traditional knowledge, International Union for Conservation of Nature, Botanical Survery of India

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Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

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Authors: Masami Usui

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Kazuo Ishiguro’s The Remains of the Day (1989) underlines another holocaust, an imprisonment of human life, dignity, and self in the globalizing sphere of the twentieth century. The Remains of the Day delineates the invisible and cruel space of “lost and found” in the postcolonial and post-imperial discourse of this century, that is, the Holocaust. The context of the concentration camp or wartime imprisonment such as Auschwitz is transplanted into the public sphere of modern England, Darlington Hall. The voice is retrieved and expressed by the young journalist and heir of Darlington Hall, Mr. David Cardinal. The new media of journalism is an intruder at Darlington Hall and plays a role in revealing the wrongly-input ideology. “Lost and Found” consists of the private and public retrieved voices. Stevens’ journey in 1956 is a return to the past, especially the period between 1935 and 1936. Lost time is retrieved on his journey; yet lost life cannot be revived entirely in his remains of life. The supreme days of Darlington Hall are the terrifying days caused by the Nazis. Fascism, terrorism, and militarism destroyed the wholesomeness of the globe. Into blind Stevens, both Miss Kenton and Mr. Cardinal bring out the common issue, that is, the political conflicts caused by Nazis. Miss Kenton expresses her own ideas against anti-Semitism regarding the Jewish maids in the crucial time when Sir Oswald Mosley’s Blackshirts organization attacked the Anglo Jews between 1935 and 1936. Miss Kenton’s half-muted statement is reinforced and assured by Cardinal in his mention of the 1934 Olympic Rally threatened by Mosley’s Blackshirts. Cardinal’s invasion of Darlington Hall embodies the increasing tension of international politics related to World War II. Darlington Hall accommodates the crucial political issue that definitely influences the fate of the house, its residents, and the nation itself and that is retrieved in the newly progressive and established media.

Keywords: modern English literature, culture studies, communication, history

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Authors: Timmis W., Simms M., Thomas C.

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This case discusses the management of two floors of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk and second primary cancer development.

Keywords: alcohol dependence, biopsy, oral carcinoma, tobacco

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Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: Anna Cameron, Chunxia Zhao, Haofei Wang, Yun Liu, Guang Ze Yang

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Since the first publication in 1775, cancer research has built a comprehensive understanding of how cellular components of the tumor niche promote disease development. However, only within the last decade has research begun to establish the impact of non-cellular components of the niche, particularly the extracellular matrix (ECM). The ECM, a three-dimensional scaffold that sustains the tumor microenvironment, plays a crucial role in disease progression. Cancer cells actively deregulate and remodel the ECM to establish a tumor-promoting environment. Recent work has highlighted the need to further our understanding of the complexity of this cancer-ECM relationship. In vitro models use hydrogels to mimic the ECM, as hydrogel matrices offer biological compatibility and stability needed for long term cell culture. However, natural hydrogels are being used in these models verbatim, without tuning their biophysical characteristics to achieve pathophysiological relevance, thus limiting their broad use within cancer research. The biophysical attributes of these gels dictate cancer cell proliferation, invasion, metastasis, and therapeutic response. Evaluating the three most widely used natural hydrogels, Matrigel, collagen, and agarose gel, the permeability, stiffness, and pore-size of each gel were measured and compared to the in vivo environment. The pore size of all three gels fell between 0.5-6 µm, which coincides with the 0.1-5 µm in vivo pore size found in the literature. However, the stiffness for hydrogels able to support cell culture ranged between 0.05 and 0.3 kPa, which falls outside the range of 0.3-20,000 kPa reported in the literature for an in vivo ECM. Permeability was ~100x greater than in vivo measurements, due in large part to the lack of cellular components which impede permeation. Though, these measurements prove important when assessing therapeutic particle delivery, as the ECM permeability decreased with increasing particle size, with 100 nm particles exhibiting a fifth of the permeability of 10 nm particles. This work explores ways of adjusting the biophysical characteristics of hydrogels by changing protein concentration and the trade-off, which occurs due to the interdependence of these factors. The global aim of this work is to produce a more pathophysiologically relevant model for each tumor type.

Keywords: cancer, extracellular matrix, hydrogel, microfluidic

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Authors: Koryukaeva Ksenia, Jinfeng Sun

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Europe has been a traditional importer of Russian natural gas for more than 50 years. In 2021, Russian state-owned company Gazprom supplied about a third of all gas consumed in Europe. The Russia-Europe mutual dependence in terms of natural gas supplies has been causing many concerns about the energy security of the two sides for a long period of time. These days the issue has become more urgent than ever considering recent Russian invasion in Ukraine followed by increased large-scale geopolitical conflicts, making the future of Russian natural gas supplies and global gas markets as well highly uncertain. Hence, the main purpose of this study is to get insight into the possible futures of Russian pipeline natural gas exports by a scenario planning method based on Monte-Carlo simulation within LUSS model framework, and propose Russian pipeline natural gas export strategies based on the obtained scenario planning results. The scenario analysis revealed that recent geopolitical disputes disturbed the traditional, longstanding model of Russian pipeline gas exports, and, as a result, the prospects and the pathways for Russian pipeline gas on the world markets will differ significantly from those before 2022. Specifically, our main findings show, that (i) the events of 2022 generated many uncertainties for the long-term future of Russian pipeline gas export perspectives on both western and eastern supply directions, including geopolitical, regulatory, economic, infrastructure and other uncertainties; (ii) according to scenario modelling results, Russian pipeline exports will face many challenges in the future, both on western and eastern directions. A decrease in pipeline gas exports will inevitably affect country’s natural gas production and significantly reduce fossil fuel export revenues, jeopardizing the energy security of the country; (iii) according to proposed strategies, in order to ensure the long-term stable export supplies in the changing environment, Russia may need to adjust its traditional export strategy by performing export flows and product diversification, entering new markets, adapting its contracting mechanism, increasing competitiveness and gaining a reputation of a reliable gas supplier.

Keywords: Russian natural gas, Pipeline natural gas, Uncertainty, Scenario simulation, Export strategy

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Authors: Mengfei Peng, Serajus Salaheen, Debabrata Biswas

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Lactobacillus casei found in the human intestine and mouth is commonly applied for dairy production. Recently, it was found that some byproducts produced by Lactobacillus exhibited antimicrobial activities against multiple bacteria. Meanwhile, introduction of prebiotic-like foods (e.g. cocoa) or probiotics or both of them as food supplements in human diets as well as in farm animal feeds is believed to be an effective ways in control/reduce the colonization of foodborne bacterial pathogens infection in the gut environment. We hypothesized that cocoa may stimulate the production antimicrobial components of Lactobacillus casei and may potentially inhibit/reduce the colonization and infection of foodborne bacterial pathogens in the gut. Mixed culture of L. casei (LC) with enterohemorrhagic E. coli EDL933 (EHEC), Salmonella Typhimurium LT2 (ST), or Listeria monocytogenes LM2 (LM) showed that LC could competitively exclude (100%) them within 72 h. Further, investigation of cell-free culture supernatant (CFCS) revealed that the antimicrobial effects of LC came from CFCS. CFCS of LC eliminated (100%) EHEC, ST, and LM within 72 h, and 2 h CFCS treatment increased the hydrophobicity of EHEC (5.10 folds), ST (8.48 folds), and LM (2.03 folds). In addition, LC cells exhibited more inhibitive effects than CFCS on cell adhesive and invasive activities of EHEC (52.14% & 90.45%), ST (66.89% & 93.83%), and LM (61.10% & 83.40%). Two clusters of poly-peptides in CFCS were identified by SDS-PAGE, the molecular weights of which are ≈5 KD and 40-45 KD. LC CFCS with overnight growth in the presence of 3% strengthened all of the antimicrobial activities (growth inhibition, outer membrane disruption, and cell infective ability reduction). Liquid chromatography/Mass spectrometry analysis detected 5 unique components in class of flavonoids in LC CFCS with overnight 3% cocoa supplement. Furthermore, qPCR results showed that CFCSs up-regulated the expression level of genes responsible for flagellin synthesis and motility, but down-regulated genes for specific binding and invasion-associated proteins synthesis. The stimulatory effects of cocoa in producing bioactive components of probiotics may aid prevention of foodborne illness caused by major foodborne enteric bacterial pathogens.

Keywords: foodborne pathogens, probiotics, prebiotics, pathogen exclusion

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Authors: Emma O’ Keeffe, Helen Hughes, Peter McLoughlin, Shiau Pin Tan, Nick McCarthy

Abstract:

Biosecurity is emerging as one of the most important issues facing the agricultural and forestry community. This is as a result of increased invasion from new pests and diseases with the main protocol for dealing with these species being the use of synthetic pesticides. However, these chemicals have been shown to exhibit negative effects on the environment. Seaweeds represent a vast untapped resource of bio-molecules with a broad range of biological activities including pesticidal. This project investigated both the antifungal and antibacterial activity of seaweed species against two problematic root rot fungi, Armillaria mellea and Heterobasidion annosum and ten quarantine bacterial plant pathogens including Xanthomonas arboricola, Xanthomonas fragariae, and Erwinia amylovora. Four seaweed species were harvested from the South-East coast of Ireland including brown, red and green varieties. The powdered seaweeds were extracted using four different solvents by liquid extraction. The poisoned food technique was employed to establish the antifungal efficacy, and the standard disc diffusion assay was used to assess the antibacterial properties of the seaweed extracts. It was found that extracts of the green seaweed exhibited antifungal activity against H. annosum, with approximately 50% inhibition compared to the negative control. The protectant activities of the active extracts were evaluated on disks of Picea sitchensis, a plant species sensitive to infection from H. annosum and compared to the standard chemical control product urea. The crude extracts exhibited very similar activity to the 10% and 20% w/v concentrations of urea, demonstrating the ability of seaweed extracts to compete with commercially available products. Antibacterial activity was exhibited by a number of seaweed extracts with the red seaweed illustrating the strongest activity, with a zone of inhibition of 15.83 ± 0.41 mm exhibited against X. arboricola whilst the positive control (10 μg/disk of chloramphenicol) had a zone of 26.5 ± 0.71 mm. These results highlight the potential application of seaweed extracts in the forestry and agricultural industries for use as biopesticides. Further work is now required to identify the bioactive molecules that are responsible for this antifungal and antibacterial activity in the seaweed extracts, including toxicity studies to ensure the extracts are non-toxic to plants and humans.

Keywords: antibacterial, antifungal, biopesticides, seaweeds

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Nandhakumar Elumalai, Purushothaman Ayyakannu, Sachidanandam T. Panchanatham

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Background: Understanding the basic mechanisms and factors underlying the tumor growth and invasion has gained attention in recent times. The processes of angiogenesis and apoptosis are known to play a vital role in various stages of cancer. The vascular endothelial growth factor (VEGF) is well established as one of the key regulators of tumor angiogenesis while MMPs are known for their exclusive ability to degrade ECM. Objective: The present study was designed to evaluate the pro apoptotic and anti angiogenic activity of the herbal formulation Shemamruthaa. The anticancer activity of Shemamruthaa was tested in breast cancer cell line (MCF-7). Results of MTT, trypan blue and flow cytometric analysis of apoptotis suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time dependent manner and induce apoptosis. With these results, we further evaluated the antiangiogenic and pro-apoptotic activities of Shemamruthaa in DMBA induced mammary carcinoma in Sprague Dawley rats. Flavono tumour was induced in 8-week-old Sprague-Dawley rats by gastric intubation of 25 mg DMBA in 1ml olive oil. After 90 days of induction period, the rats were orally administered with Shemamruthaa (400 mg/kg body wt) for 45 days. Treatment with the drug SM significantly modulated the expression of p53, MMP-2, MMP-3, MMP-9 and VEGF by means of its anti angiogenic and protease inhibiting activity. Conclusion: Based on these results, it might be concluded that the formulation, Shemamruthaa, constituted of dried flowers of Hibiscus rosa-sinensis, fruits of Emblica officinalis, and honey has been found to exhibit pronounced antiproliferative and apoptotic effects. This enhanced anticancer effect of Shemamruthaa might be attributed to the synergistic action of polyphenols such as flavonoids, tannins, alkaloids, glycosides, saponins, steroids, terpenoids, vitamin C, niacin, pyrogallol, hydroxymethylfurfural, trilinolein, and other compounds present in the formulation. Collectively, these results demonstrate that Shemamruthaa holds potential to be developed as a potent chemotherapeutic agent against mammary carcinoma.

Keywords: Shemamruthaa, flavonoids, MCF-7 cell line, mammary cancer

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