Search results for: expression recognition

Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder

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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.

Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance

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Authors: Jawaher Bakheet Almudarra

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An Educational Supervisor assists teachers to develop their competence and skills in teaching, solving educational problems, and to improve the teaching methods to suit the educational process. They evaluate their teachers and write reports based on their assessments. In 1957, the Saudi Ministry of Education instituted Educational Supervision to facilitate effective management of schools, however, there have been concerns that the Educational Supervision has not been effective in executing its mandate. Studies depicted that Educational supervision has not been effective because it has been marred by poor and autocratic leadership practices such as stringent inspection, commanding and judging. Therefore, there is need to consider some of the ways in which school outcomes can be enhanced through the improvement of Educational supervision practices. Emotional intelligence is a relatively new concept that can be integrated into the Saudi education system that is yet to be examined in-depth and embraced particularly in the realm of educational leadership. Its recognition and adoption may improve leadership practices among Educational supervisors. This study employed a qualitative interpretive approach that will focus on decoding, describing and interpreting the connection between emotional intelligence and leadership. The study also took into account the social constructions that include consciousness, language and shared meanings. The data collection took place in the Office of Educational Supervisors in Riyadh and involved 4 Educational supervisors and 20 teachers from both genders- male and female. The data collection process encompasses three methods namely; qualitative emotional intelligence self-assessment questionnaires, reflective semi-structured interviews, and open workshops. The questionnaires would explore whether the Educational supervisors understand the meaning of emotional intelligence and its significance in enhancing the quality of education system in Saudi Arabia. Subsequently, reflective semi-structured interviews were carried out with the Educational supervisors to explore the connection between their leadership styles and the way they conceptualise their emotionality. The open workshops will include discussions on emotional aspects of Educational supervisors’ practices and how Educational supervisors make use of the emotional intelligence discourse in their leadership and supervisory relationships.

Keywords: directors of educational supervision, emotional intelligence, educational leadership, education management

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Authors: Jigg Pelayo, Ricardo Villar

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The Philippines is long considered as a valuable producer of high value crops globally. The country’s employment and economy have been dependent on agriculture, thus increasing its demand for the efficient agricultural mechanism. Remote sensing and geographic information technology have proven to effectively provide applications for precision agriculture through image-processing technique considering the development of the aerial scanning technology in the country. Accurate information concerning the spatial correlation within the field is very important for precision farming of high value crops, especially. The availability of height information and high spatial resolution images obtained from aerial scanning together with the development of new image analysis methods are offering relevant influence to precision agriculture techniques and applications. In this study, an algorithm was developed and implemented to detect and count high value crops simultaneously through adaptive scaling of support vector machine (SVM) algorithm subjected to object-oriented approach combining watershed transformation and local maxima filter in enhancing tree counting and detection. The methodology is compared to cutting-edge template matching algorithm procedures to demonstrate its effectiveness on a demanding tree is counting recognition and delineation problem. Since common data and image processing techniques are utilized, thus can be easily implemented in production processes to cover large agricultural areas. The algorithm is tested on high value crops like Palm, Mango and Coconut located in Misamis Oriental, Philippines - showing a good performance in particular for young adult and adult trees, significantly 90% above. The s inventories or database updating, allowing for the reduction of field work and manual interpretation tasks.

Keywords: high value crop, LiDAR, OBIA, precision agriculture

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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Authors: Mohammad Hossein Habibi, Atena Sadat Hosseini

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Colorectal cancer is the third leading cause of cancer-related death in the world. Colorectal cancer screening, early detection, and treatment programs could benefit from the most up-to-date information on the disease's burden, given the present worldwide trend of increasing colorectal cancer incidence. Tumor recurrence and resistance are exacerbated by the presence of chemotherapy-resistant cancer stem cells that can generate rapidly proliferating tumor cells. In addition, tumor cells can evolve chemoresistance through adaptation mechanisms. In this work, we used in silico analysis to select suitable GEO datasets. In this study, we compared slow-growing cancer stem cells with high-growth colorectal cancer-derived cancer stem cells. We then evaluated the signal pathways, transcription factors, and kinases associated with these two types of cancer stem cells. A total of 980 upregulated genes and 870 downregulated genes were clustered. MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Fc gamma R-mediated phagocytosis, and Steroid biosynthesis signaling pathways were observed in upregulated genes. Also, caffeine metabolism, amino sugar and nucleotide sugar metabolism, TNF signaling pathway, and cytosolic DNA-sensing pathway were involved in downregulated genes. In the next step, we evaluated the best transcription factors and kinases in two types of cancer stem cells. In this regard, NR2F2, ZEB2, HEY1, and HDGF as transcription factors and PRDM5, SMAD, CBP, and KDM2B as critical kinases in upregulated genes. On the other hand, IRF1, SPDEF, NCOA1, and STAT1 transcription factors and CTNNB1 and CDH7 kinases were regulated low expression genes. Using bioinformatics analysis in the present study, we conducted an in-depth study of colorectal cancer stem cells at low and high growth rates so that we could take further steps to detect and even target these cells. Naturally, more additional tests are needed in this direction.

Keywords: colorectal cancer, bioinformatics analysis, transcription factor, kinases, cancer stem cells

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Authors: Wen Zhen

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Compared to content words, function words have been relatively overlooked by English learners especially articles. The article system, to a certain extent, becomes a resistance to know English better, driven by different elements. Three principal factors can be summarized in term of the nature of the articles when referring to the difficulty of the English article system. However, making the article system more complex are difficulties in the second acquisition process, for [-ART] learners have to create another category, causing even most non-native speakers at proficiency level to make errors. According to the sequences of acquisition of the English article, it is showed that the zero article is first acquired and in high inaccuracy. The zero article is often overused in the early stages of L2 acquisition. Although learners at the intermediate level move to underuse the zero article for they realize that the zero article does not cover any case, overproduction of the zero article even occurs among advanced L2 learners. The aim of the study is to investigate noun-phrase factors which give rise to incorrect usage or overuse of the zero article, thus providing suggestions for L2 English acquisition. Moreover, it enables teachers to carry out effective instruction that activate conscious learning of students. The research question will be answered through a corpus-based, data- driven approach to analyze the noun-phrase elements from the semantic context and countability of noun-phrases. Based on the analysis of the International Thurber Thesis corpus, the results show that: (1) Although context of [-definite,-specific] favored the zero article, both[-definite,+specific] and [+definite,-specific] showed less influence. When we reflect on the frequency order of the zero article , prototypicality plays a vital role in it .(2)EFL learners in this study have trouble classifying abstract nouns as countable. We can find that it will bring about overuse of the zero article when learners can not make clear judgements on countability altered from (+definite ) to (-definite).Once a noun is perceived as uncountable by learners, the choice would fall back on the zero article. These findings suggest that learners should be engaged in recognition of the countability of new vocabulary by explaining nouns in lexical phrases and explore more complex aspects such as analysis dependent on discourse.

Keywords: noun phrase, zero article, corpus, second language acquisition

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Authors: Wang Huiwen

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Since its release, Toni Morrison's novel Beloved has garnered significant international recognition, and its adaptation of a historical account has profoundly affected readers and scholars, evoking a visceral understanding of the suffering endured by black slaves. The ecofeminist approach has garnered more attention in recent times. The emergence of ecofeminism may be attributed to the feminist movement, which has subsequently evolved into several branches, including cultural ecofeminism, social ecofeminism, and socialist ecofeminism, each of which is developing its own specific characteristics. The many branches hold differing perspectives, yet they all converge on a key principle: the interconnectedness between the subjugation of women and the exploitation of nature can be traced back to a common underlying cognitive framework. Scholarly investigations into the novel Beloved have primarily centered on the cultural interpretations around the emancipation of African American women, with a predominant lens rooted in cultural ecofeminism. This thesis aims to analyze Morrison's feminist beliefs in the novel Beloved by integrating socialist and cultural ecofeminist perspectives, which seeks to challenge the limitations of essentialism within ecofeminism while also proposing a strategy to address exploitation and dismantle oppressive structures depicted in Beloved. This thesis examines the white patriarchal oppression system underlying the relationships between men and women, blacks and whites, and man and nature as shown in the novel. What the black women have been deprived of compared with the black men, white women and white men is a main clue of this research, while nature is a key complement of each chapter for their loss. The attainment of spiritual redemption and ultimate freedom is contingent upon the social revolution that enables bodily emancipation, both of which are indispensable for black women. The weighty historical pains, traumatic recollections, and compromised sense of self prompted African slaves to embark on a quest for personal redemption. The restoration of the bond between black men and women, as well as the relationship between black individuals and nature, is a clear and undeniable pathway towards the final freedom of black women in the novel Beloved.

Keywords: beloved, ecofeminism, black women, nature, essentialism

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Authors: Li Yang, Yang Song, Martin Y. M. Chiang

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Objective: To experimentally substantiate the micromechanical compatibility between cell and scaffold, in the regenerative medicine approach for restoring bone volume, is essential for phenotypic transitions Methods: Through nanotechnology and electrospinning process, nanofibrous scaffolds were fabricated to host dental follicle stem cells (DFSCs). Blends (50:50) of polycaprolactone (PCL) and silk fibroin (SF), mixed with various content of cellulose nanocrystals (CNC, up to 5% in weight), were electrospun to prepare nanofibrous scaffolds with heterogeneous microstructure in terms of fiber size. Colloidal probe atomic force microscopy (AFM) and conventional uniaxial tensile tests measured the scaffold stiffness at the micro-and macro-scale, respectively. The cell elastic modulus and cell-scaffold adhesive interaction (i.e., a chemical function) were examined through single-cell force spectroscopy using AFM. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine if the mechanotransduction signal (i.e., Yap1, Wwr2, Rac1, MAPK8, Ptk2 and Wnt5a) is upregulated by the scaffold stiffness at the micro-scale (cellular scale). Results: The presence of CNC produces fibrous scaffolds with a bimodal distribution of fiber diameter. This structural heterogeneity, which is CNC-composition dependent, remarkably modulates the mechanical functionality of scaffolds at microscale and macroscale simultaneously, but not the chemical functionality (i.e., only a single material property is varied). In in vitro tests, the osteogenic differentiation and gene expression associated with mechano-sensitive cell markers correlate to the degree of micromechanical compatibility between DFSCs and the scaffold. Conclusion: Cells require compliant scaffolds to encourage energetically favorable interactions for mechanotransduction, which are converted into changes in cellular biochemistry to direct the phenotypic evolution. The micromechanical compatibility is indeed important to the efficacy of regenerative medicine.

Keywords: phenotype transition, scaffold stiffness, electrospinning, cellulose nanocrystals, single-cell force spectroscopy

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Authors: Kamsiah Jaarin, Yusof Kamisah, Faizah Othman Nurul Akmal Muhammad, Zakiah Jubri, Qodriyah Mohd Saad, Srijit Das

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Forty (40) normotensive adult male Sprague-Dawley rats aged three months weighing 180-200 g were divided into 4 groups with 10 rats per group: (1) normotensive control; (2) hypertensive rats; (3) hypertensive rats treated with Nigella sativa (2.5 ml/kg/day); and (4) hypertensive rats treated with nicardipine (5 mg/kg/day). After acclimatization, the hypertensive rats of the group 2, 3 and 4 were induced to be hypertensive by giving NW–nitro-L-arginine methyl ester (L-NAME; 30 mg/kg/day) in their drinking water for consecutive 7 days. After one week, rats in the group 3 were given a daily oral dose of 2.5 ml/kg/day of Nigella sativa (NS) by oral gavage. Rats in the group 4 were given nicardipine (5 mg/kg/day) via oral gavages. All rats in this study received L-NAME continuously throughout the treatment duration. The blood pressure will be measured pre-treatment and weekly for 8 weeks using power lab. Blood was taken before and at the end of study for measurement of nitric oxide. At the end of 8 weeks, the rats are sacrificed and descending thoracic aorta was disserted for measurement of vascular reactivity, and intracellular adhesion molecules (ICAM-1) and vascular cell adhesion molecules (VCAM-1). Nigella sativa reduced both systolic and diastolic BP compared to control and L-name group. The BP lowering effect of NS was comparable to nicardipine a calcium antagonist. The blood pressure lowering effect of NS was accompanied with an increasing relaxation response to nitroprusside and acetylcholine and reducing vasoconstriction response to epinephrine. L-NAME and nicardipine on the other hand, reduced plasma nitric oxide concentration. In contrast, NS increased NO concentration. However, Nigella sativa had no significant effect on aortic VCAM- 1 and ICAM-1 expression. In conclusion; Nigella sativa oil reduces both systolic and diastolic blood pressure in L-NAME treated rats. The antihypertensive effect of NS was comparable to nicardipine. The BP lowering effect may be mediated via stimulating nitric oxide release from vascular endothelium.

Keywords: Nigella sativa, ICAM, VCAM, blood pressure, vascular reactivity

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Authors: Mahdi Sepehrmanesh

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This essay explores Gerald Vizenor's innovative concepts of the tragedy of absence and the comedy of presence as frameworks for understanding and challenging dominant narratives about Native American identity and history. Vizenor's work critiques the notion of irrevocable cultural loss and rigid definitions of Indigenous identity based on blood quantum and stereotypical practices. Through subversive humor, trickster figures, and storytelling, Vizenor asserts the active presence and continuance of Native peoples, advocating for a dynamic, self-determined understanding of Native identity. The essay examines Vizenor's use of postmodern techniques, including his engagement with simulation and hyperreality, to disrupt colonial discourses and create new spaces for Indigenous expression. It explores the concept of "crossblood" identities as a means of resisting essentialist notions of Native authenticity and embracing the complexities of contemporary Indigenous experiences. Vizenor's ideas of survivance and transmotion are analyzed as strategies for cultural resilience and adaptation in the face of ongoing colonial pressures. The interplay between absence and presence in Vizenor's work is discussed, particularly through the lens of shadow survivance and the power of storytelling. The essay also delves into Vizenor's critique of terminal creed and his promotion of natural reason as an alternative epistemology to Western rationalism. While acknowledging the significant influence of Vizenor's work on Native American literature and theory, the essay also addresses critiques of his approach, including concerns about the accessibility of his writing and its political effectiveness. Despite these debates, the essay argues that Vizenor's concepts offer a powerful vision of Indigenous futurity that is rooted in tradition yet open to change, inspiring hope and agency in the face of oppression. By examining Vizenor's multifaceted approach to Native American identity and presence, this essay contributes to ongoing discussions about Indigenous representation, cultural continuity, and resistance to colonial narratives in literature and beyond.

Keywords: gerald vizenor, identity native american literature, survivance, trickster discourse, identity

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Authors: Salma A. El-Marasy, Rehab F. Abdel-Rahman, Reham M. Abd-Elsalam

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The burden of stroke is intensely increasing worldwide. Brain injury following transient or permanent focal cerebral ischemia develops ischemic stroke as a consequence of a complex series of pathophysiological events. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent on its insulinotropic properties in non-diabetic rats subjected to cerebral ischemia. Anaesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24h following reperfusion. 48h following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in the biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological score deficit, locomotor activity and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphorylated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted the neuroprotective effect in a dose-dependent manner as shown in amelioration of neuronal cell loss and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, it’s anti-oxidant property, activation of PI3K/AKT/mTOR pathway and its anti-apoptotic effect.

Keywords: caspase-3, cerebral ischemia, dipeptidyl peptidase-4 inhibitor, oxidative stress, PI3K/AKT/mTOR pathway, rats, vildagliptin

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Authors: Nibedita Priyadarsini

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It is said that Ethics has a wide range of application which mainly deals with human life and human behavior. All ethical decisions are ultimately concerned with life and death. Both life and death must be considered dignified. Medical ethics with its different topics mostly deals with life and death concepts among which euthanasia is one. Various types of debates continue over Euthanasia long since. The question of putting an end to someone’s life has aroused controversial in legal sphere as well as in moral sphere. To permit or not to permit has remained an enigma the world over. Modern medicine is in the stage of transcending limits that cannot be set aside. The morality of allowing people to die without treatment has become more important as methods of treatment have become more sophisticated. Allowing someone to die states an essential recognition that there is some point in any terminal illness when further curative treatment has no purpose and the patient in such situation should allow dying a natural death in comfort, peace, and dignity, without any interference from medical science and technology. But taking a human life is in general sense is illogical in itself. It can be said that when we kill someone, we cause the death; whereas if we merely let someone die, then we will not be responsible for anyone’s death. This point is often made in connection with the euthanasia cases and which is often debatable. Euthanasia in the pediatric age group involves some important issues that are different from those of adult issues. The main distinction that occurs is that the infants and newborns and young children are not able to decide about their future as the adult does. In certain cases, where the child born with some serious deformities with no hope of recovery, in that cases doctor decide not to perform surgery in order to remove the blockage, and let the baby die. Our aim in this paper is to examine, whether it is ethically justified to withhold or to apply euthanasia on the part of the defective infant. What to do with severely defective infants from earliest time if got to know that they are not going to survive at all? Here, it will deal mostly with the ethics in deciding the relevant ethical concerns in the practice of euthanasia with the defective newborns issues. Some cases in relation to disabled infants and newborn baby will be taken in order to show what to do in a critical condition, that the patient and family members undergoes and under which condition those could be eradicated, if not all but some. The final choice must be with the benefit of the patient.

Keywords: ethics, medical ethics, euthanasia, defective newborns

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Authors: Tugce Duygu Koksal

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In recent years, given the fact that the acts of terrorism and the threat of the latter are taking place without any border and distinction, it has led the states to deal with the terrorism as a priority issue. More recently, as seen in different countries during state of emergency, the adoption of anti-terrorism measures motivated by the sole need of the prevention of terrorism targets directly the fundamental rights of individuals. Therefore, a contribution to the understanding of the value of the principle of legality is becoming more and more important nowadays. This paper aims to reflect the probable effects of the adoption of anti-terrorism measures regardless of the principle of legality, on the fundamental rights. In this respect, this paper will first discuss the margin of appreciation of the national authorities by countering terrorism, and then, the importance of the respect of the legality of the anti-terrorism measures will be examined in the light of actual examples. Indeed, one of the major findings of this study is the fact that the anti-terrorism laws and measures were taken in this framework must be subject to close scrutiny in democracies, which adopted the principle of the rule of law and respect human rights. Although the state's margin of appreciation in the field of counter-terrorism is broad, these measures which are based on the legitimate aim of a democracies’ legitimate right to protect itself against the activities of terrorist organizations should have the legal basis and be strictly required by the exigencies of the fight against terrorism. While combating terrorism, the legal basis shall only be achieved if the legal consequences of an individuals’ actions related to terrorism shall be clear and foreseeable by the individuals of a society. On the other hand, particularly during the state of emergency, the ambiguity of the law might be used to include a wide range of actions under acts of terrorism. This is becoming more dangerous where freedom of expression, freedom of the press, freedom of association and the right to information is in the substance of these actions. Disregarding the principle of legality is susceptible to create a chilling effect on the exercise of human rights, and therefore, the fight against terrorism can be transformed into a repressive regime on opponents. As a result, the efforts to counter terrorism of the national authorities irrespective of the principle of legality are susceptible to cause a transformation of the rule of law to a state of law which cannot be appreciated in a democratic society.

Keywords: anti-terrorism measures, chilling effect, predictability, the principle of legality, state of emergency

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Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

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Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

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Authors: Patricia Portugal Marques de Carvalho Lourenco

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A three-phase methodological multi-lingual path was designed, constructed and carried out using the 2020 Chinese Internet Drama Series We Are All Alone as a case study. Phase one, the backbone of the research, comprised of secondary data analysis, providing the structure on which the next two phases would be built on. Phase one incorporated a Google Scholar and a Baidu Index analysis, Star Network Influence Index and Mydramalist.com top two drama reviews, along with an article written about the drama and scrutiny of Chinese related blogs and websites. Phase two was field research elaborated across Latin Europe, and phase three was social media focused, having into account that perceptions are going to be memory conditioned based on past ideas recall. Overall, research has shown the poor cultural expression of Chinese entertainment in Latin Europe and demonstrated the inexistence of Chinese content in French, Italian, Portuguese and Spanish Business to Consumer retailers; a reflection of their low significance in Latin European markets and the short-life cycle of entertainment products in general, bubble-gum, disposable goods without a mid to long-term effect in consumers lives. The process of conducting comprehensive international research was complex and time-consuming, with data not always available in Mandarin, the researcher’s linguistic deficiency, limited Chinese Cultural Knowledge and cultural equivalence. Despite steps being taken to minimize the international proposed research, theoretical limitations concurrent to Latin Europe and China still occurred. Data accuracy was disputable; sampling, data collection/analysis methods are heterogeneous; ascertaining data requirements and the method of analysis to achieve a construct equivalence was challenging and morose to operationalize. Secondary data was also not often readily available in Mandarin; yet, in spite of the array of limitations, research was done, and results were produced.

Keywords: research methodologies, international research, primary data, secondary data, research limitations, online dramas, china, latin europe

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Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

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In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

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Authors: Luiz Nolasco Jr. Rezende, Antonio Villar M. Sá, Claudia Marcia L. Pato

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The increasing urban violence in Brazil involves more and more infractions committed by children and youths. The challenges faced by the institutional environments responsible for the education and resocialization of adolescents in conflict with the law are enormous, especially of those deprived of their liberty. These institutions have an inadequate educational structure. They are characterized by a dirty and unhealthy environment without the minimum basic conditions for their activities, by frequent practices of degradation, humiliation, and the physical and psychological punishment of inmates. This mixed-method study investigated the personal values of adolescents with restriction of freedom in a socio-educational institutional environment aiming to contribute to the development of their morality through an educational process. For that, we used a survey and transdisciplinary play workshops involving thirty-two boys aged between 15 and 19 years old and at least two years out of school. To evaluate the survey the reduced version of the Portrait Questionnaire—PQ21—was used. The workshops happened once a week, lasting 80 minutes each, totaling twelve meetings. By using the game of chess and its metaphors, participants produced texts and engaged in critical brainstorming about their lives. The survey results pointed out that these young people showed a predominance of values of openness to change and self-transcendence, dissatisfaction with one's own reality and surroundings, not considering the consequences of their actions on themselves and others, difficulties in speaking and writing, and desire for changes in their lives. After the pedagogical interventions, these adolescents demonstrated an understanding of the implications of their actions for themselves, for their families, especially for the mothers, with whom they demonstrated stronger bonds. It was possible to observe evidence of improvement in the capacity of linguistic expression, more autonomy and critical vision, including about themselves and their respective contexts. These results demonstrated the educational potential of lively, symbolic, dynamic and playful activities that favor the mediation and identification of these adolescents with their lives, and contribute to the projection of dreams.

Keywords: adolescents arrested, human values, moral development, playful workshops

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Authors: Achitphol Chookaew, Paramee Thongsukhsai, Patamarerk Engsontia, Narongwit Nakwan, Pritsana Raugrut

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Lung cancer is one of the most common malignancies and primary cause of death due to cancer worldwide. Non-small cell lung cancer (NSCLC) is the main subtype in which majority of patients present with advanced-stage disease. Herein, we analyzed differentially expressed genes to find potential biomarkers for lung cancer diagnosis as well as prognostic markers. We used transcriptome data from our 2 NSCLC patients and public data (GSE81089) composing of 8 NSCLC and 10 normal lung tissues. Differentially expressed genes (DEGs) between NSCLC and normal tissue and between early-stage and late-stage NSCLC were analyzed by the DESeq2. Pairwise correlation was used to find the DEGs with false discovery rate (FDR) adjusted p-value £ 0.05 and |log2 fold change| ³ 4 for NSCLC versus normal and FDR adjusted p-value £ 0.05 with |log2 fold change| ³ 2 for early versus late-stage NSCLC. Bioinformatic tools were used for functional and pathway analysis. Moreover, the top ten genes in each comparison group were verified the expression and survival analysis via GEPIA. We found 150 up-regulated and 45 down-regulated genes in NSCLC compared to normal tissues. Many immnunoglobulin-related genes e.g., IGHV4-4, IGHV5-10-1, IGHV4-31, IGHV4-61, and IGHV1-69D were significantly up-regulated. 22 genes were up-regulated, and five genes were down-regulated in late-stage compared to early-stage NSCLC. The top five DEGs genes were KRT6B, SPRR1A, KRT13, KRT6A and KRT5. Keratin 6B (KRT6B) was the most significantly increased gene in the late-stage NSCLC. From GEPIA analysis, we concluded that IGHV4-31 and IGKV1-9 might be used as diagnostic biomarkers, while KRT6B and KRT6A might be used as prognostic biomarkers. However, further clinical validation is needed.

Keywords: differentially expressed genes, early and late-stages, gene ontology, non-small cell lung cancer transcriptomics

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Authors: Hacer Kobya Bulut, Kıymet Yeşilçiçek Çalık, Birsel Canan Demirbağ, Hacer Erdöl, Songül Aktaş

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Introduction: As an expression of an emotion which always exists in life, crying is regarded as one of the problematic behaviors of patients by nurses. Towards such patients, nurses may exhibit emotional and behavioral reactions such as feeling helpless, anger, indifferent, defense, and opposition. However crying either meets a need, reduces the tension to cope with problems or helps patient to gain strength. Therefore, nurses must accept that crying is a normal mechanism that reduces emotional tension and should approach a crying patient accordingly. Objective: This study was carried out to evaluate the communicational behaviors of the nurses towards ‘crying patient’. Methods: This descriptive study was conducted with the nurses working at a university hospital in a city in the Eastern Black Sea in June-September 2015. The entire universe was tried to be reached without sampling. 90% of the population was reached and the study was completed with 309 nurses who volunteered to participate in the study. Data were collected through a questionnaire which was prepared reviewing the literature by researchers. Data were evaluated in SPSS analysis program using percentages, numbers and chi-square test with the 95% confidence interval and p <0.05significance level. Findings: The findings showed that the average age of nurses was 31.52 ± 7.96, work experience was 10:09 ± 7.69 and only 22.7% had training about ‘approach to crying patient’ during their education. 97.1% of the nurses often faced with crying patients in their professional lives, 62.8% stated that they faced crying women patients. When they see crying patients, 84.8% of the nurses ‘do not want the patient to cry’, 80.9% wonder ‘why they are crying’, % 79.6 ‘feel uneasiness’,% 79.3 ‘feel sorry’ and 41.4% ‘ feel helpless’. The question ‘Why do you think the patient is crying?’ was answered by 93.5% nurses as ‘they are suffering’, by 86.1% ‘they are helpless’, 80.9% ‘they are sad’, 79.6% ‘they need help’, 54.4% ‘because they feel inadequate,’ and 44.7% ‘they fail to control their crying behavior. ‘How do you approach to your patient when she/he is crying?’ question was answered by 82.5% of nurses as ‘I would console’, 77.3% as ‘I would ask the reason’, 63.1% as ‘I would try to stop her from crying’ all of which are actually inappropriate nursing approaches. However, 92.2% of the nurses stated that ‘I do not judge the crying patient’, ‘87.1% said ‘I allocate time to crying patients’ and 85.8% said ‘ I ask patient whether they want to cry alone’. The study showed that educational background and work experience of the nurses affected the appropriate approach to crying patients (P <0.05). Conclusion: As a result of the study, it was found out that nurses do not want patients to cry, so they exhibit inappropriate approach such as consoling the patients and they have difficulty in approaching crying patients.

Keywords: approach to patient, communication, crying patient, nurse, Turkey

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Authors: Adamnesh A. Bogale, Dorte Thorsen

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This paper aims to learn how children/siblings left behind due to parental migration experience care and the effects of the separation. It also aims to unpack the experiences of youth migrants in rural Ethiopia. It focuses specifically on how children and youth are affected in order to highlight in which areas intervention can enhance or inadvertently undermine the development impact of migration on young people. Based on a qualitative study in South Wollo, Ethiopia, which was undertaken in three stages in 2017-19 and involved 34 households and a number of key informants, the analysis offers insights into how migration contributes to household sustainability and, in the process, alters intergenerational relationships and dynamics. Contemporary migration in Ethiopia is complex and highly gendered. For young women, the migration corridor from Ethiopia to the Middle East is the most important, whereas young men mostly engage in local migration or travel to South Africa or Sudan. Arguing that children and youths’ experience of migration must be understood in the context of the moral, affective, and material economies, the paper distinguishes between young people’s experiences of migration as children of migrants, as siblings of a migrant, and as migrants. The material shows that children and youths demonstrate different experiences in parental migration depending on age, care arrangement, and the ability to communicate with an absent mother. Migration has a different implication for younger siblings depending on their gender. The division of work and future responsibilities post marriage combine to disadvantage female siblings while male siblings are either unaffected or reaped the benefits of investments made with remittances. Finally, migration is a mechanism to change generational power relationships. As remitters, young migrants yield better recognition in the family, though not always to the degree that they can control the use of remittances. The power to make decisions is not tied only to material resources and the household; migration facilitates social change that opens space for young women to have more influence over their own lives.

Keywords: migration, youth, Ethiopia, generations

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Authors: S. Kozlovski, S.W. Feigelson, R. Alon

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The b2 integrin ligands ICAM-1 ICAM-2 and the endothelial VLA-4 integrin ligand VCAM-1 are constitutively expressed on different lung vessels and on high endothelial venules (HEVs), the main portal for lymphocyte entry from the blood into lung draining lymph nodes. ICAMs are also ubiquitously expressed by many antigen-presenting leukocytes and have been traditionally suggested as critical for the various antigen-specific immune synapses generated by these distinct leukocytes and specific naïve and effector T cells. Loss of both ICAM-1 and ICAM-2 on the lung vasculature reduces the ability to patrol monocytes and Tregs to patrol the lung vasculature at a steady state. Our new findings suggest, however, that in terms of innate leukocyte trafficking into the lung lamina propria, both constitutively expressed and virus-induced vascular VCAM-1 can functionally compensate for the loss of these ICAMs. In a mouse model for influenza infection, neutrophil and NK cell recruitment and clearance of influenza remained normal in mice deficient in both ICAMs. Strikingly, mice deficient in both ICAMs also mounted normal influenza-specific CD8 proliferation and differentiation. In addition, these mice normally combated secondary influenza infection, indicating that the presence of ICAMs on conventional dendritic cells (cDCs) that present viral antigens are not required for immune synapse formation between these APCs and naïve CD8 T cells as previously suggested. Furthermore, long-lasting humoral responses critical for protection from a secondary homosubtypic influenza infection were also normal in mice deficient in both ICAM-1 and ICAM-2. Collectively, our results suggest that the expression of ICAM-1 and ICAM-2 on lung endothelial and epithelial cells, as well as on DCs and B cells, is not critical for the generation of innate or adaptive anti-viral immunity in the lungs. Our findings also suggest that endothelial VCAM-1 can substitute for the functions of vascular ICAMs in leukocyte trafficking into various lung compartments.

Keywords: emigration, ICAM-1, lymph nodes, VCAM-1

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Authors: Milagros S. Salibad, Levita B. Grana

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The presence and role of Indigenous Peoples residing in key biodiversity, protected, and watershed areas within the ancestral domain in the Caraga Region hold immense significance. This study aimed to determine the level of biodiversity conservation practices among the Mamanwas, Manobos, and Higaonons, and identify facilitating or hindering factors. Employing a mixed-method research design, 421 respondents participated through a researcher-made questionnaire. Focus group discussions, key informant interviews, researcher field notes, community immersions, and secondary sources were done. The three groups have demonstrated a high level of biodiversity conservation practices manifesting their commitment to conserving their natural resources and ecosystems. Evidently, selecting and cutting only mature trees for shelter and tribal usage, and preservation of large trees that harbor ancestors’ spirits and worship through rituals (Mambabaja). Each group exhibited unique environmental practices shaped by their distinct cultures, traditions, customary knowledge, and access to information. The Mamanwa practiced traditional hunting and gathering by using traps while Manobo practiced shifting cultivation to maintain soil fertility and biodiversity, and Higaonon managed forest resources through traditional forest management (establishment of sacred forests and conservation areas). Various facilitating and hindering factors influenced their conservation efforts. Their traditional knowledge and practices, partnership and collaboration, legal recognition and support, access to information, and biodiversity monitoring system facilitate practices. Insufficient government assistance, political and social issues, scarce financial support, inadequate policy enforcement, lack of livelihood opportunities, and land use conflicts hinder them. Monitoring the sustainability of IPs' local biodiversity conservation practices is essential as they contribute to conservation endeavors.

Keywords: biodiversity, conservation, indigenous peoples, traditional knowledge

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Authors: Wanderson Goncalves e Goncalves, José Alberto Silva de Sá

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Human actions are a threat to the balance and conservation of the Amazon forest. Therefore the environmental monitoring services play an important role as the preservation and maintenance of this environment. This study classified forest types using data from a forest inventory provided by the 'Florestal e da Biodiversidade do Estado do Pará' (IDEFLOR-BIO), located between the municipalities of Santarém, Juruti and Aveiro, in the state of Pará, Brazil, covering an area approximately of 600,000 hectares, Bands 3, 4 and 5 of the TM-Landsat satellite image, and Self - Organizing Maps. The information from the satellite images was extracted using QGIS software 2.8.1 Wien and was used as a database for training the neural network. The midpoints of each sample of forest inventory have been linked to images. Later the Digital Numbers of the pixels have been extracted, composing the database that fed the training process and testing of the classifier. The neural network was trained to classify two forest types: Rain Forest of Lowland Emerging Canopy (Dbe) and Rain Forest of Lowland Emerging Canopy plus Open with palm trees (Dbe + Abp) in the Mamuru Arapiuns glebes of Pará State, and the number of examples in the training data set was 400, 200 examples for each class (Dbe and Dbe + Abp), and the size of the test data set was 100, with 50 examples for each class (Dbe and Dbe + Abp). Therefore, total mass of data consisted of 500 examples. The classifier was compiled in Orange Data Mining 2.7 Software and was evaluated in terms of the confusion matrix indicators. The results of the classifier were considered satisfactory, and being obtained values of the global accuracy equal to 89% and Kappa coefficient equal to 78% and F1 score equal to 0,88. It evaluated also the efficiency of the classifier by the ROC plot (receiver operating characteristics), obtaining results close to ideal ratings, showing it to be a very good classifier, and demonstrating the potential of this methodology to provide ecosystem services, particularly in anthropogenic areas in the Amazon.

Keywords: artificial neural network, computational intelligence, pattern recognition, unsupervised learning

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Authors: Berkan Ural, Arif Eser, Sinan Apaydin

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Medical image processing is generally become a challenging task nowadays. Indeed, processing of brain MRI images is one of the difficult parts of this area. This study proposes a hybrid well-defined approach which is consisted from tumor detection, extraction and analyzing steps. This approach is mainly consisted from a computer aided diagnostics system for identifying and detecting the tumor formation in any region of the brain and this system is commonly used for early prediction of brain tumor using advanced image processing and probabilistic neural network methods, respectively. For this approach, generally, some advanced noise removal functions, image processing methods such as automatic segmentation and morphological operations are used to detect the brain tumor boundaries and to obtain the important feature parameters of the tumor region. All stages of the approach are done specifically with using MATLAB software. Generally, for this approach, firstly tumor is successfully detected and the tumor area is contoured with a specific colored circle by the computer aided diagnostics program. Then, the tumor is segmented and some morphological processes are achieved to increase the visibility of the tumor area. Moreover, while this process continues, the tumor area and important shape based features are also calculated. Finally, with using the probabilistic neural network method and with using some advanced classification steps, tumor area and the type of the tumor are clearly obtained. Also, the future aim of this study is to detect the severity of lesions through classes of brain tumor which is achieved through advanced multi classification and neural network stages and creating a user friendly environment using GUI in MATLAB. In the experimental part of the study, generally, 100 images are used to train the diagnostics system and 100 out of sample images are also used to test and to check the whole results. The preliminary results demonstrate the high classification accuracy for the neural network structure. Finally, according to the results, this situation also motivates us to extend this framework to detect and localize the tumors in the other organs.

Keywords: image processing algorithms, magnetic resonance imaging, neural network, pattern recognition

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Authors: S. Junaid S. Qazi, Denice C. Bay, Raymond Chew, Raymond J. Turner

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EmrE, a member of the small multidrug resistance protein family in bacteria is considered to be the archetypical member of its family. It confers host resistance to a wide variety of quaternary cation compounds (QCCs) driven by proton motive force. Generally, purification yield is a challenge in all membrane proteins because of the difficulties in their expression, isolation and solubilization. EmrE is extremely hydrophobic which make the purification yield challenging. We have purified EmrE protein using two different approaches: organic solvent membrane extraction and hexahistidine (his6) tagged Ni-affinity chromatographic methods. We have characterized changes present between ligand affinity of untagged and his6-tagged EmrE proteins in similar membrane mimetic environments using biophysical experimental techniques. Purified proteins were solubilized in a buffer containing n-dodecyl-β-D-maltopyranoside (DDM) and the conformations in the proteins were explored in the presence of four QCCs, methyl viologen (MV), ethidium bromide (EB), cetylpyridinium chloride (CTP) and tetraphenyl phosphonium (TPP). SDS-Tricine PAGE and dynamic light scattering (DLS) analysis revealed that the addition of QCCs did not induce higher multimeric forms of either proteins at all QCC:EmrE molar ratios examined under the solubilization conditions applied. QCC binding curves obtained from the Trp fluorescence quenching spectra, gave the values of dissociation constant (Kd) and maximum specific one-site binding (Bmax). Lower Bmax values to QCCs for his6-tagged EmrE shows that the binding sites remained unoccupied. This lower saturation suggests that the his6-tagged versions provide a conformation that prevents saturated binding. Our data demonstrate that tagging an integral membrane protein can significantly influence the protein.

Keywords: small multidrug resistance (SMR) protein, EmrE, integral membrane protein folding, quaternary ammonium compounds (QAC), quaternary cation compounds (QCC), nickel affinity chromatography, hexahistidine (His6) tag

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Authors: Stephen Wagman

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This paper identifies three common structures in English sentences that are important for understanding academic texts, regardless of the characteristics or background of the readers or whether they are reading English as a second or a foreign language. Adapting a model from the Humanities, the explication of texts used in literary studies, the paper analyses sample sentences to reveal structures that enable the reader not only to decide which words are necessary for understanding the main ideas but to make the decision without knowing the meaning of the words. By their very syntax noun structures point to the key word for understanding them. As a rule, the key noun is followed by easily identifiable prepositions, relative pronouns, or verbs and preceded by single adjectives. With few exceptions, the modifiers are unnecessary for understanding the idea of the sentence. In addition, sentences are often structured by lists in which the items frequently consist of parallel groups of words. The principle of a list is that all the items are similar in meaning and it is not necessary to understand all of the items to understand the point of the list. This principle is especially important when the items are long or there is more than one list in the same sentence. The similarity in meaning of these items enables readers to reduce sentences that are hard to grasp to an understandable core without excessive use of a dictionary. Finally, the idea of subordination and the identification of the subordinate parts of sentences through connecting words makes it possible for readers to focus on main ideas without having to sift through the less important and more numerous secondary structures. Sometimes a main idea requires a subordinate one to complete its meaning, but usually, subordinate ideas are unnecessary for understanding the main point of the sentence and its part in the development of the argument from sentence to sentence. Moreover, the connecting words themselves indicate the functions of the subordinate structures. These most frequently show similarity and difference or reasons and results. Recognition of all of these structures can not only enable students to read more efficiently but to focus their attention on the development of the argument and this rather than a multitude of unknown vocabulary items, the repetition in lists, or the subordination in sentences are the one necessary element for comprehension of academic articles.

Keywords: development of the argument, lists, noun structures, subordination

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Authors: Aidan Battison, Neliswa Mama

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Environmental pollution by ionic species has been identified as one of the biggest challenges to the sustainable development of communities. The widespread use of organic and inorganic chemical products and the release of toxic chemical species from industrial waste have resulted in a need for advanced monitoring technologies for environment protection, remediation and restoration. Some of the disadvantages of conventional sensing methods include expensive instrumentation, well-controlled experimental conditions, time-consuming procedures and sometimes complicated sample preparation. On the contrary, the development of fluorescent chemosensors for biological and environmental detection of metal ions has attracted a great deal of attention due to their simplicity, high selectivity, eidetic recognition, rapid response and real-life monitoring. Coumarin derivatives S1 and S2 (Scheme 1) containing 1,2,3-triazole moieties at position -3- have been designed and synthesized from azide and alkyne derivatives by CuAAC “click” reactions for the detection of metal ions. These compounds displayed a strong preference for Fe3+ ions with complexation resulting in fluorescent quenching through photo-induced electron transfer (PET) by the “sphere of action” static quenching model. The tested metal ions included Cd2+, Pb2+, Ag+, Na+, Ca2+, Cr3+, Fe3+, Al3+, Cd2+, Ba2+, Cu2+, Co2+, Hg2+, Zn2+ and Ni2+. The detection limits of S1 and S2 were determined to be 4.1 and 5.1 uM, respectively. Compound S1 displayed the greatest selectivity towards Fe3+ in the presence of competing for metal cations. S1 could also be used for the detection of Fe3+ in a mixture of CH3CN/H¬2¬O. Binding stoichiometry between S1 and Fe3+ was determined by using both Jobs-plot and Benesi-Hildebrand analysis. The binding was shown to occur in a 1:1 ratio between the sensor and a metal cation. Reversibility studies between S1 and Fe3+ were conducted by using EDTA. The binding site of Fe3+ to S1 was determined by using 13 C NMR and Molecular Modelling studies. Complexation was suggested to occur between the lone-pair of electrons from the coumarin-carbonyl and the triazole-carbon double bond.

Keywords: chemosensor, "click" chemistry, coumarin, fluorescence, static quenching, triazole

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Authors: Thomais Tsoulia, Arvind Y. M. Sundaram, Stine Braaen, Øyvind Haugland, Espen Rimstad, Øystein Wessel, Maria K. Dahle

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Fish red blood cells (RBC) are nucleated, and in addition to their function in gas exchange, they have been characterized as mediators of immune responses. Salmonid RBC are the major target cells of Piscineorthoreovirus (PRV), a virus associated with heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon. The activation of antiviral response genesin RBChas previously been described in ex vivo and in vivo PRV-infection models, but not explored in the initial virus encounter phase. In the present study, mRNA transcriptome responses were explored in erythrocytes from individual fish, kept ex vivo, and exposed to purified PRV for 24 hours. The responses were compared to responses in macrophage-like salmon head kidney (SHK-1) and endothelial-like Atlantic salmon kidney (ASK) cells, none of which support PRV replication. The comparative analysis showed that the antiviral response to PRV was strongest in the SHK-1 cells, with a set of 80 significantly induced genes (≥ 2-fold upregulation). In RBC, 46 genes were significantly upregulated, while ASK cells were not significantly responsive. In particular, the transcriptome analysis of RBC revealed that PRV significantly induced interferon regulatory factor 1 (IRF1) and interferon-induced protein with tetratricopeptide repeats 5-like (IFIT9). However, several interferon-regulated antiviral genes which have previously been reported upregulated in PRV infected RBC in vivo (myxovirus resistance (Mx), interferon-stimulated gene 15 (ISG15), toll-like receptor 3 (TLR3)), were not significantly induced after 24h of virus stimulation. In contrast to RBC, these antiviral response genes were significantly upregulated in SHK-1. These results confirm that RBC are involved in the innate immune response to viruses, but with a delayed antiviral response compared to SHK-1. A notable difference is that interferon regulatory factor 1 (IRF-1) is the most strongly induced gene in RBC, but not among the significantly induced genes in SHK-1. Putative differences in the binding, recognition, and response to PRV, and any link to effects on the ability of PRV to replicate remains to be explored.

Keywords: antiviral responses, atlantic salmon, piscine orthoreovirus-1, red blood cells, RNA-seq

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Authors: Kai Pai Huang

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Background: There are several types of plasma cell neoplasms including multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are found in our lab. Today, we want to compare with two cases using the method of capillary electrophoresis. Method: Serum is prepared and electrophoresis is performed at alkaline PH in a capillary using the Sebia® Capillary 2. Albumin and globulins are detected by the detector which is located in the cathode of the capillary and the signals are transformed to peaks. Serum was treated with beta-mercaptoethanol which reducing the polymerized immunoglobulin to monomer immunoglobulin to clarify two M-protein are secreted from the same plasma cell clone in bone marrow. Result: Case 1: A 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria, leukocytosis, results of high serum IgA and lambda light chain. A renal biopsy found amyloid fibrils in the glomerular mesangial area. Serum protein electrophoresis shows a major monoclonal peak in the β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. Case 2: A 55-year-old male presenting abdominal distension and low back pain for more than one month. Laboratory data showed T12 T8 compression fracture, results of high serum IgM and kappa light chain. Bone marrow aspiration showed the cells from the bone marrow are B cells with monotypic kappa chain expression. Bone marrow biopsy found this is lymphoplasmacytic lymphoma (Waldenstrom macroglobulin). Serum protein electrophoresis shows a monoclonal peak in the β region and the immunotyping studies for serum showed IgM/κ type. Conclusion: Plasma cell neoplasm can be diagnosed by many examinations. Among them, using capillary electrophoresis by a lab can separate several types of gammopathy and the quantification of a monoclonal peak can be used to evaluate the patients’ prognosis or treatment.

Keywords: plasma cell neoplasm, capillary electrophoresis, serum protein electrophoresis, immunotyping

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Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi

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Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.

Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53

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