Search results for: up regulated

Authors: Christos Konstantopoulos, Thomas Ussmueller

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Digital low drop-out regulators, in contrast to analog counterparts, provide an architecture of sub-1 V regulation with low power consumption, high power efficiency, and system integration. Towards an optimized integration in the ultra-low-power system-on-chip Internet of Things architecture that is operated through a radio frequency energy harvesting scheme, the D-LDO regulator should constitute the main regulator that operates the master-clock and rest loads of the SoC. In this context, we present a D-LDO with linear search coarse regulation and asynchronous fine regulation, which incorporates an in-regulator clock generation unit that provides an autonomous, self-start-up, and power-efficient D-LDO design. In contrast to contemporary D-LDO designs that employ ring-oscillator architecture which start-up time is dependent on the frequency, this work presents a fast start-up burst oscillator based on a high-gain stage with wake-up time independent of coarse regulation frequency. The design is implemented in a 55-nm Global Foundries CMOS process. With the purpose to validate the self-start-up capability of the presented D-LDO in the presence of ultra-low input power, an on-chip test-bench with an RF rectifier is implemented as well, which provides the RF to DC operation and feeds the D-LDO. Power efficiency and load regulation curves of the D-LDO are presented as extracted from the RF to regulated DC operation. The D-LDO regulator presents 83.6 % power efficiency during the RF to DC operation with a 3.65 uA load current and voltage regulator referred input power of -27 dBm. It succeeds 486 nA maximum quiescent current with CL 75 pF, the maximum current efficiency of 99.2%, and 1.16x power efficiency improvement compared to analog voltage regulator counterpart oriented to SoC IoT loads. Complementary, the transient performance of the D-LDO is evaluated under the transient droop test, and the achieved figure-of-merit is compared with state-of-art implementations.

Keywords: D-LDO, Internet of Things, RF energy harvesting, voltage regulators

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Authors: Payal Maheshwari, Maheaswari Brindavan

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The present study aimed at studying the level of perceived self-efficacy of children with learning disability and their mother’s perception about the efficacy of the child and the relationship between the two. The study further aimed at finding out the relationship between the level of perceived self-efficacy of children with learning disability and their academic achievement and their mother’s perception about the Efficacy of the child and child’s Academic Achievement. The sample comprised of 80 respondents (40 children with learning disability and their mothers). Children with learning disability as their primary condition, belonging to middle or upper middle class, living with both the parents, residing in Mumbai and their mothers were selected. Purposive or judgmental and snowball sampling technique was used to select the sample for the present study. Proformas in the form of questionnaires were used to obtain the background information of the children with learning disability and their mother’s. A self-constructed Mother’s Perceived Efficacy of their Child Assessment Scale was used to measure mothers perceived level of efficacy of their child with learning disability. Self-constructed Child’s Perceived Self-Efficacy Assessment Scale was used to measure the level of child’s perceived self-efficacy. Academic scores of the child were collected from the child’s parents or teachers and were converted into percentage. The data were analyzed quantitatively using frequencies, mean and standard deviation. Correlations were computed to ascertain the relationships between the different variables. The findings revealed that majority of the mother’s perceived efficacy about their child with learning disability was above average as well as majority of the children with learning disability also perceived themselves as having above average level of self-efficacy. Further in the domains of self-regulated learning and emotional self-efficacy majority of the mothers perceived their child as having average or below average efficacy, 50% of the children also perceived their self-efficacy in the two domains at average or below average level. A significant (r=.322, p < .05) weak correlation (Spearman’s rho) was found between mother’s perceived efficacy about their child, and child’s perceived self-efficacy and a significant (r=.377, p < .01) weak correlation (Pearson Correlation) was also found between mother’s perceived efficacy about their child and child’s academic achievement. Significant weak positive correlation was found between child’s perceived self-efficacy and academic achievement (r=.332, p < .05). Based on the findings, the study discussed the need for intervention program for children in non-academic skills like self-regulation and emotional competence.

Keywords: learning disability, perceived self efficacy, academic achievement, mothers, children

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Authors: Pujiyono, Reda Manthovani, Deny Tri Ardianto, Rabani Halawa, Isharyanto

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This research has background that the taxpayer (defendant) who has paid off the tax payable and the tax penalty payable after the tax case file has been transferred to the court, while the legality of stopping the prosecution of tax cases on the grounds that in the interest of state revenue is not regulated in the provisions of Law Number 8 of 1981 concerning The Criminal Procedure Code and Law Number 28 of 2007 concerning the Third Amendment to Law Number 6 of 1983 concerning General Provisions and Tax Procedures as amended several times, most recently by Law Number 16 of 2009 concerning Stipulation of Government Regulation in Lieu of Law Number 5 of 2008 concerning Fourth Amendment to Law Number 6 0f 1983 concerning General Provisions and Tax Procedures to become Law, even though at the investigation stage it regulates the mechanism for stopping the investigation for the sake of the interest of acceptance ne this is because before the case file is transferred to the court where at the request of the Minister of Finance of The Republic of Indonesia can stop the investigation in the interest of state revenue so that based on this phenomenon a legal vacuum is found. Therefore, a non-penal policy is needed from the public prosecutor to resolve tax crime cases without going through litigation in court through the penal mediation method using the Plea Bargaining System which adheres to the principles of restorative justice and obligative justice based on the ultimum remedium principle and the principle of opportunity in order to realize the principle of fast, simple and low cost justice (content principle). This research is a normative legal research, using a statutory approach, conceptual approach, and comparative law approach. Regulations that is used in many countries, include America, The Netherlands and Singapore. The results of this study indicate that there is a reformulation of the tax criminal justice system which regulates the mechanism, qualifications and authority to terminate the prosecution of tax cases in the interest of state revenues in order to achieve legal goals which are not only for legal certainty but more that, namely providing benefits and legal justice for people seeking justice.

Keywords: obligative justice, regulation, state reveneus, tax criminal

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Authors: Hoang Thi Quynh, Shima Kazuto

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Organic farming is gaining interest in Vietnam. However, organic fertilizer production is not sufficiently regulated, resulting in unknown quality. This study investigated characteristics of so-called organic fertilizers in the Vietnam’s market and their mineralization in soil-plant system. We collected 15 commercial products (11 domestic and 4 imported) which labelled 'organic fertilizer' in the market to analyze nutrients composition. A 20 day-incubation experiment was carried on with 80 g sandy-textured soil, amended with the fertilizer at a rate of 109.4 mgN.kg⁻¹soil in 150 mL glass bottle at 25℃. We categorized them according to nutrients content and mineralization rate, and then selected 8 samples for cultivation experiment. The experiment was conducted by growing Komatsuna (Brassica campestris) in sandy-textured soil using an automatic watering apparatus in a greenhouse. The fertilizers were applied to the top one-third of the soil stratum at a rate of 200 mgN.kg⁻¹ soil. Our study also analyzed material flow of coffee husk compost in Central Highland of Vietnam. Total N, P, K, Ca, Mg and C: N ratio varied greatly cross the domestic products, whereas they were quite similar among the imported materials. The proportion of inorganic-N to T-N of domestic products was higher than 25% in 8 of 11 samples. These indicate that N concentration increased dramatically in most domestic products compared with their raw materials. Additionally, most domestic products contained less P, and their proportions of Truog-P to T-P were greatly different. These imply that some manufactures were interested in adjusting P concentration, but some ones were not. Furthermore, the compost was made by mixing with chemical substances to increase nutrients content (N, P), and also added construction surplus soil to gain weight before packing product to sell in the market as 'organic fertilizer'. There was a negative correlation between C:N ratio and mineralization rate of the fertilizers. There was a significant difference in N efficiency among the fertilizer treatments. N efficiency of most domestic products was higher than chemical fertilizer and imported organic fertilizers. These results suggest regulations on organic fertilizers production needed to support organic farming that is based on internationally accepted standards in Vietnam.

Keywords: inorganic N, mineralization, N efficiency, so-called organic fertilizers, Vietnam’s market

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Authors: Singh Deepeshwar, N. K. Manjunath, M. Avinash

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Meditation is a self-regulated conscious process associated with improved awareness, perception, attention and overall performance. Different traditional origin of meditation technique may have different effects on autonomic activity and brain functions. Based on this quest, the present study evaluated the effect of Tai-Chi Chuan (TCC, a Chines movement based meditation technique) and Cyclic Meditation (CM, an Indian traditional based stimulation and relaxation meditation technique) on the hemodynamic responses of the prefrontal cortex (PFC) and autonomic functions (such as R-R interval of heart rate variability and respiration). These two meditation practices were compared with simple walking. Employing 64 channel near infrared spectroscopy (NIRS), we measured hemoglobin concentration change (i.e., Oxyhemoglobin [ΔHbO], Deoxyhemoglobin [ΔHbR] and Total hemoglobin change [ΔTHC]) in the bilateral PFC before and after TCC, CM and Walking in young college students (n=25; average mean age ± SD; 23.4 ± 3.1 years). We observed the left PFC activity predominantly modulates sympathetic activity effects during the Tai-Chi whereas CM showed changes on right PFC with vagal dominance. However, the changes in oxyhemoglobin and total blood volume change after Tai-Chi was significant higher (p < 0.05, spam t-maps) on the left hemisphere, whereas after CM, there was a significant increase in oxyhemoglobin (p < 0.01) with a decrease in deoxyhemoglobin (p < 0.05) on right PFC. The normal walking showed decrease in Oxyhemoglobin with an increase in deoxyhemoglobin on left PFC. The autonomic functions result showed a significant increase in RR- interval (p < 0.05) along with significant reductions in HR (p < 0.05) in CM, whereas Tai-chi session showed significant increase in HR (p < 0.05) when compared to walking session. Within a group analysis showed a significant reduction in RR-I and significant increase in HR both in Tai-chi and walking sessions. The CM showed there were a significant improvement in the RR - interval of HRV (p < 0.01) with the reduction of heart rate and breath rate (p < 0.05). The result suggested that Tai-Chi and CM both have a positive effect on left and right prefrontal cortex and increase sympathovagal balance (alertful rest) in autonomic nervous system activity.

Keywords: brain, hemodynamic responses, yoga, meditation, Tai-Chi Chuan (TCC), walking, heart rate variability (HRV)

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Authors: Hassan Okati-Aliabad, Athare Nazri-Panjaki, Mahdi Mohammadi, Alireza Ansari-Moghaddam

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Aims: In type 2 diabetes control, self-management is an effective way to minimize the risk of developing complications and improve the quality of life. Self-determination theory (SDT) proposed a promising explanatory framework to predict self-regulated behavior, which was particularly relevant to self-management. This study aimed to investigate whether SDT constructs can affect the self-management and controlling glycated hemoglobin A1c levels in type 2 diabetic patients or not. Methods: This cross-sectional study was conducted from August to December 2022 at two diabetes clinics in Zahedan, Iran. The study included 300 patients with type 2 diabetes. Data collection was done using a researcher-administrated questionnaire that included demographic data, diabetes self-care activities, and self-determination constructs including autonomous support, autonomous motivation, and perceived competence. Results: The mean of the overall score of self-care activities was 34.62 ±11.86 out of a maximum of 70. Patients in the fourth quarter (wealthiest) of the socioeconomic status had the highest mean self-care score (P=0.003). There was a significant relationship between diet score with perceived competence (P=0.009). Perceived competence (P˂0.001) and controlled self-regulation (P˂0.001) were the predictors of exercise scores in diabetes patients. Independent self-regulation (P˂0.001, r=0.21) and overall self-regulation (P=0.001,r=0.19) were significantly related to blood-glucose testing scores. There was a significant relationship between foot care score with perceived competence (P=0.048, r=0.11) and autonomous support (P=0.013, r=0.14). Multiple regression showed that exercise was the predictor of HbA1c (P=0.014). Conclusion: Exercise is crucial for achieving good individualized glycemic control and reducing the risk of diabetes complications. The findings provided valuable insights into the determinants of self-care activities in patients with type 2 diabetes and underscore the need for interventions that address socioeconomic disparities, enhance perceived competence, and provide autonomy support to improve diabetes self-care.

Keywords: self-care activities, diabetes mellitus type 2, blood glucose self-monitoring, health behaviors, self-determination theory

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Authors: Eitan Yefenof

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Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.

Keywords: apoptosis, leukemia, micro-RNA, steroids

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Authors: Latife Merve Oktay, Berrin Tugrul

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Hydroxytyrosol (HT) is a phenolic phytochemical molecule derived from the hydrolysis of oleuropein, which originates during the maturation of the olives. It has recently received particular attention because of its antioxidant, anti-proliferative, pro-apoptotic and anti-inflammatory activities. In this study, we investigated the cytotoxic and apoptotic effects of hydroxytyrosol and its effects on phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways in human ovarian cancer cell lines OVCAR-3 and MDAH-2774. XTT cell proliferation kit, Cell Death Detection Elisa Plus Kit (Roche) and Human Apoptosis Array (R&D Systems) were used to determine the cytotoxic and apoptotic effects of HT in OVCAR-3 and MDAH-2774 cell lines at 24, 48, 72, and 96 h. Effect of HT on PI3K/Akt and ERK 1/2 signaling pathways were investigated by using specific inhibitors of these pathways. IC50 values of HT were found to be 102.3 µM in MDAH-2774 cells at 72 h and 51.5 µM in OVCAR-3 cells at 96 h. Apoptotic effect of HT in MDAH-2774 cells was the highest at 50 µM at 72 h, and kept decreasing at 100 and 150 µM concentrations and was not seen at 200 µM and higher concentrations. Highest apoptotic effect was seen at 100 µM concentration in OVCAR-3 cells at 96 h, however apoptotic effect was decreased over 100 µM concentrations. According to antibody microarray results, HT increased the levels of pro-apoptotic molecules Bad, Bax, active caspase-3, Htra2/Omi by 2.0-, 1.4-, 1.2-, 4.2-fold, respectively and also increased the levels of pro-apoptotic death receptors TRAIL R1/DR4, TRAIL R2/DR5, FAS/TNFRSF6 by 2.1-, 1.7-, 1.6-fold, respectively, however, it decreased the level of Survivin by 1.6-fold which is one of the inhibitor of apoptosis protein (IAP) family in MDAH-2774 cells. In OVCAR-3 cells, HT decreased the levels of anti-apoptotic proteins Bcl-2, pro-caspase 3 by 3.1-, 8.2-fold, respectively and IAP family proteins CIAP-1, CIAP-2, XIAP, Livin, Survivin by 6.5-, 6.0-, 3.2-, 2.2-, 2.7-fold, respectively and increased the level of cytochrome-c by 1.2-fold. We have shown that HT shows its cytotoxic and apoptotic effect through inhibiting ERK 1/2 signaling pathway in both OVCAR-3 and MDAH-2774 cells. Further studies are needed to investigate molecular mechanisms and modulatory effects of hydroxytyrosol.

Keywords: apoptosis, cytotoxicity, hydroxytyrosol, ovarian cancer

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Authors: Camila Freire Barrios, Gonzalo Rivera Talavera

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The importance of public spaces has been shown for many years, and in different disciplines, with one example being their ability for developing a sustainable social environment, especially in mega cities like Lima. The aim of this study was to explore the process of space appropriation that occurs in the Peripheral Library of the district El Agustino in Lima, Peru. Space appropriation is a process by which people develop a link with a place within a specific sociocultural context. This process has been related to positive outcomes, such as: participation and in the development of compassionate behaviors with these places. To achieve the purpose of the research, a qualitative design was selected because this will allowed exploring in deep the process in an specific context. The study interviewed six adults, all of whom were deliberately chosen to have the longest residence time in the district and also utilized the library the most. In a complementary manner, two children and one adolescent were interviewed. Likewise, two observations were made on a weekday and weekend, and public documentation information was collected. As a result, five categories linked to this process were identified. It was found that the process of space appropriation begins with the needs of the people who arrive at the library, which provides benefits to these people by fulfilling them. Next in the process, through the construction of meanings, the library is then valued as a pleasant, productive, safe and regulated place; as a result, people become identified with the library. The identification generated is subsequently reflected in the level of participation that the person has in the library, which may go in a continuum from no participating at all to a more direct involvement in the library activities, as well as voluntary and altruistic work. Finally, this process leads to the library becoming part of the neighborhood. This study allows having a better understanding of how sociospatial processes work in a Latinamerican context and in cities like Lima, where the third of the country’s population lives. Also, Lima has grown in the past 50 years in a excessively way and with lack of planification. Therefore, these results brings new research questions and highlights the importance of learning how to design public spaces in order to promote these processes to develop.

Keywords: bond with the place, place identity, public spaces, space appropriation

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Authors: Ahmad Khoirul Umam

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This paper investigates the role of vested interests and its impacts on anti-corruption agenda in Indonesia following the collapse of authoritarian regime in 1998. A pervasive and rampant corruption has been believed as the main cause of the state economy’s fragility. Hence, anti-corruption measures were implemented by applying democratization and market liberalization since the establishment of a consolidated democracy which go hand in hand with a liberal market economy is convinced to be an efficacious prescription for effective anti-corruption. The reform movement has also mandated the establishment of the independent, neutral and professional special anti-corruption agency namely Corruption Eradication Commission (KPK) to more intensify the fight against the systemic corruption. This paper will examine whether these anti-corruption measures have been effective to combat corruption, and investigate to what extend have the anti-corruption efforts, especially those conducted by KPK, been impeded by the emergence of a nexus of vested interests as the side-effect of democratization and market liberalization. Based on interviews with key stakeholders from KPK, other law enforcement agencies, government, prominent scholars, journalists and NGOs in Indonesia, it is found that since the overthrow of Soeharto, anti-corruption movement in the country have become more active and serious. After gradually winning the hearth of people, KPK successfully touched the untouchable corruption perpetrators who were previously protected by political immunity, legal protection and bureaucratic barriers. However, these changes have not necessarily reduced systemic and structural corruption practices. Ironically, intensive and devastating counterattacks were frequently posed by the alignment of business actors, elites of political parties, government, and also law enforcement agencies by hijacking state’s instruments to make KPK deflated, powerless, and surrender. This paper concludes that attempts of democratization, market liberalization and the establishment of anti-corruption agency may have helped Indonesia to reduce corruption. However, it is still difficult to imply that such anti-corruption measures have fostered the more effective anti-corruption works in the newly democratized and weakly regulated liberal economic system.

Keywords: vested interests, democratization, market liberalization, anti-corruption, Indonesia

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Authors: Rachit Ahuja, Ayush Chugh

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Aerodynamic forces and moments, as well as tire-road forces largely affects the maneuverability of the vehicle. Car manufacturers are largely fascinated and influenced by various aerodynamic improvements made in formula cars. There is constant effort of applying these aerodynamic improvements in road vehicles. In motor racing, the key differentiating factor in a high performance car is its ability to maintain highest possible acceleration in appropriate direction. One of the main areas of concern in motor racing is balance of aerodynamic forces and stream line the flow of air across the body of the vehicle. At present, formula racing cars are regulated by stringent FIA norms, there are constrains for dimensions of the vehicle, engine capacity etc. So one of the fields in which there is a large scope of improvement is aerodynamics of the vehicle. In this project work, an attempt has been made to design a formula- student (FS) car, improve its aerodynamic characteristics through steady state CFD simulations and simultaneously calculate its lap time. Initially, a CAD model of a formula student car is made using SOLIDWORKS as per the given dimensions and a steady-state external air-flow simulation is performed on the baseline model of the formula student car without any add on device to evaluate and analyze the air-flow pattern around the car and aerodynamic forces using FLUENT Solver. A detailed survey on different add-on devices used in racing application like: - front wing, diffuser, shark pin, T- wing etc. is made and geometric model of these add-on devices are created. These add-on devices are assembled with the baseline model. Steady state CFD simulations are done on the modified car to evaluate the aerodynamic effects of these add-on devices on the car. Later comparison of lap time simulation of the formula student car with and without the add-on devices is done with the help of MATLAB. Aerodynamic performances like: - lift, drag and their coefficients are evaluated for different configuration and design of the add-on devices at different speed of the vehicle. From parametric CFD simulations on formula student car attached with add-on devices, there is a considerable amount of drag and lift force reduction besides streamlining the airflow across the car. The best possible configuration of these add-on devices is obtained from these CFD simulations and also use of these add-on devices have shown an improvement in performance of the car which can be compared by various lap time simulations of the car.

Keywords: aerodynamic performance, front wing, laptime simulation, t-wing

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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: 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: Ines Nitoi, Petruta Oancea, Lucian Constantin, Laurentiu Dinu, Maria Crisan, Malina Raileanu, Ionut Cristea

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2,4,6-Trinitrotoluene (TNT) is the most common pollutant identified in wastewater generated from munitions plants where this explosive is synthesized or handled (munitions load, assembly and pack operations). Due to their toxic and suspected carcinogenic characteristics, nitroaromatic compounds like TNT are included on the list of prioritary pollutants and strictly regulated in EU countries. Since their presence in water bodies is risky for human health and aquatic life, development of powerful, modern treatment methods like photocatalysis are needed in order to assures environmental pollution mitigation. The photocatalytic degradation of TNT was carried out at pH=7.8, in aqueous TiO2 based catalyst suspension, under sunlight irradiation. The enhanced photo activity of catalyst in visible domain was assured by 0.5% Fe doping. TNT degradation experiments were performed using a tubular collector type solar photoreactor (26 UV permeable silica glass tubes series connected), plug in a total recycle loops. The influence of substrate concentration and catalyst dose on the pollutant degradation and mineralization by-products (NO2-, NO3-, NH4+) formation efficiencies was studied. In order to compare the experimental results obtained in various working conditions, the pollutant and mineralization by-products measured concentrations have been considered as functions of irradiation time and cumulative photonic energy Qhν incident on the reactor surface (kJ/L). In the tested experimental conditions, at tens mg/L pollutant concentration, increase of 0,5%-TiO2 dose up to 200mg/L leads to the enhancement of CB degradation efficiency. Since, doubling of TNT content has a negative effect on pollutant degradation efficiency, in similar experimental condition, prolonged irradiation time from 360 to 480 min was necessary in order to assures the compliance of treated effluent with limits imposed by EU legislation (TNT ≤ 10µg/L).

Keywords: wastewater treatment, TNT, photocatalysis, environmental engineering

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Authors: Seong Gu Hwang, Young Kyoon Oh, Joseph F. dela Cruz

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Marbling, or intramuscular fat, has been consistently identified as one of the top beef quality problems. Intramuscular adipocytes distribute throughout the perimysial connective tissue of skeletal muscle and are the major site for the deposition of intramuscular fat, which is essential for the eating quality of meat. The stromal vascular fraction of the skeletal muscle contains progenitor cells that can be enhanced to differentiate to adipocytes and increase intramuscular fat. Primary cultures of bovine intramuscular stromal vascular cells were used in this study to elucidate the effects of extracellular calcium and retinoic acid concentration on adipocyte differentiation. Cell viability assay revealed that even at different concentrations of calcium and retinoic acid, there was no significant difference on cell viability. Monitoring of the adipocyte differentiation showed that bovine intramuscular stromal vascular cells cultured in a low concentration of extracellular calcium and retinoic acid had a better degree of fat accumulation. The mRNA and protein expressions of PPARγ, C/EBPα, SREBP-1c and aP2 were analyzed and showed a significant upregulation upon the reduction in the level of extracellular calcium and retinoic acid. The upregulation of these adipogenic related genes means that the decreasing concentration of calcium and retinoic acid is able to stimulate the adipogenic differentiation of bovine intramuscular stromal vascular cells. To further elucidate the effect of calcium, the expression level of calreticulin was measured. Calreticulin which is known to be an inhibitor of PPARγ was down regulated by the decreased level of calcium and retinoic acid in the culture media. The same tendency was observed on retinoic acid receptors RARα and CRABP-II. These receptors are recognized as adipogenic inhibitors, and the downregulation of their expression allowed a better level of differentiation in bovine intramuscular stromal vascular cells. In conclusion, data show that decreasing the level of extracellular calcium and retinoic acid can significantly promote adipogenesis in intramuscular stromal vascular cells of Hanwoo beef cattle. These findings may provide new insights in enhancing intramuscular adipogenesis and marbling in beef cattle.

Keywords: calcium, calreticulin, hanwoo beef, retinoic acid

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Authors: Amina Aloui, Jalila Ben Salah-Abbès, Abdellah Zinedine, Amar Riba, Noel Durand, Catherine Brabet, Didier Montet, Samir Abbès

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Mycotoxin contamination of food and feed-isa globaconcern, both economically and for public health. Aflatoxin M1 (AFM1) is the principal hydroxylated metabolite of aflatoxin B1. It is frequently found in milk and other dairy products. It is responsible for the development of hepatocellular carcinoma and immunotoxic in humans and animals. The reduction of its bioavailabilitybecomesa great demand in order to protect human and animal health. The use of probiotic bacteria and clay are demonstrated to be able to bind AFM1 in vitro. This study aimed to investigate, in vivo, the activity of two-component mixture: L. rhamnosusGAF06 (LR) and bentonite for reducing the oxidative stress and the histological alterationsinduced by AFM1 in the liver andkidneys. For the experiment, male mice were divided into 7 groups (6 mice/group) and treated, orally, by AFM1, alone or in combination with LR and/or bentonite, for 10 days as follows: group 1 control, group 2 treated with LR alone (2.108 CFU/ml), group 3 treated with bentonite alone (1g/kg), group 4 treated with AFM1 alone (100μg/kg), group 5 co-treated with LR+AFM1, group 6 co-treated with bentonite+AFM1, group 7 co-treated with bentonite+LR+AFM1. At the end of the treatment, the mice were sacrificed, and the livers and kidneys were collected for histological assays. Intracellular antioxidant activities and lipid peroxidation were also studied. The results showed that AFM1causeddamage in liver and kidney tissues, being evidence of hepatotoxicity and nephrotoxicity marked by necrotic cells. It increased the MDA level and decreased the antioxidant enzyme activities (SOD) in both organs. In contrast, the co-treatment with AFM1 plus LR and/or bentonitesignificantly improved the hepatic and renal tissues, regulated kidney, and liver antioxidant enzyme activities. This improvement was more remarkable with the administration of LR-bentonite mixture with AFM1.LR and bentonite alone showed to be safe during the treatment. This mixture can be a promising candidate for future applications in biotechnological processes that aimed to detoxify AFM1in food and feed.

Keywords: aflatoxin M1, bentonite, L. rhamnosus GAF06, oxidative stress, prevention

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Authors: Tamara Roma, Emma Capulli

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Pregnancy and fertility, in other words, reproduction, has become, in the last half of the century, increasingly and globally controlled, medicalized, and regulated. The reflection proposed starts from the consequences of the inscription of reproduction into the neoliberal economic paradigm. The new biotechnologies developments have raised a new patriarchal justification for State’s control of uterus bodies and a new construction of knowledge about reproductive health. Moral discussion and juridification remove reproduction and non-reproduction from their personal and intimate context and frame them under words like “duties”, “rights”, “family planning”, “demography”, and “population policy”, reinvent them as “States business” and ultimately help to re/confirm a specific construct of fertility, motherhood, and family. Moreover, the interaction between the neoliberal economy and medical biotechnologies brought about a new formulation of the connection between feminine generative potential and value production. The widespread and contemporary debates on Medically Assisted Reproduction (MAR), surrogacy and abortion suggest the need for a “feminist/queer global bioethical discourse” capable of inserting itself into the official bioethical debate characterized by the traditional dichotomy of laic bioethics/Catholic bioethics. The contribution moves from a feminist bioethics perspective on reproductive technologies to introduce a feminist/queer global bioethics point of view on reproductive health. The comparison between reproduction and non-reproduction debates is useful to analyze and demonstrate how restrictive legislations, dichotomic bioethical discussion and medical control confirm and strengthens gender injustice in reproductive life. In fact, MAR, surrogacy, and abortion restrictions stem from a shared social and legal paradigm that depends on traditional gender roles revealing how the stratification of reproduction is based on multiple discrimination along the lines of gender, race, and class. In conclusion, the perspective of feminist/queer global bioethics tries to read the concept of universal reproductive justice, introducing an original point of view on reproductive health access.

Keywords: queer bioethics, reproductive health, reproductive justice, reproductive technologies

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Authors: Evren Isen

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In grid-connected renewable energy systems, input power is controlled by AC/DC converter or/and DC/DC converter depending on output voltage of input source. The power is injected to DC-link, and DC-link voltage is regulated by inverter controlling the grid current. Inverter performance is considerable in grid-connected renewable energy systems to meet the utility standards. In this paper, modelling and simulation of hysteresis current controlled single-phase grid-connected inverter that is utilized in renewable energy systems, such as wind and solar systems, are presented. 2 kW single-phase grid-connected inverter is simulated in Simulink and modeled in Matlab-m-file. The grid current synchronization is obtained by phase locked loop (PLL) technique in dq synchronous rotating frame. Although dq-PLL can be easily implemented in three-phase systems, there is difficulty to generate β component of grid voltage in single-phase system because single-phase grid voltage exists. Inverse-Park PLL with low-pass filter is used to generate β component for grid angle determination. As grid current is controlled by constant bandwidth hysteresis current control (HCC) technique, average switching frequency and variation of switching frequency in a fundamental period are considered. 3.56% total harmonic distortion value of grid current is achieved with 0.5 A bandwidth. Average value of switching frequency and total harmonic distortion curves for different hysteresis bandwidth are obtained from model in m-file. Average switching frequency is 25.6 kHz while switching frequency varies between 14 kHz-38 kHz in a fundamental period. The average and maximum frequency difference should be considered for selection of solid state switching device, and designing driver circuit. Steady-state and dynamic response performances of the inverter depending on the input power are presented with waveforms. The control algorithm regulates the DC-link voltage by adjusting the output power.

Keywords: grid-connected inverter, hysteresis current control, inverter modelling, single-phase inverter

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Authors: Pelin Balcik Ercin

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Introduction: ZEB transcription factor family member ZEB2, has a role in epithelial to mesenchymal transition during development and metastasis. The altered circulating extracellular miRNAs expression is observed in diseases, and extracellular miRNAs have an important role in cancer cell microenvironment. In ChIP-Seq study, the expression of miR-2110 was found to be regulated by ZEB2. In this study, the effects of miR2110 on cell proliferation and migration of hepatocellular carcinoma (HCC) cells were examined. Material and Methods: SNU398 cells transfected with mimic miR2110 (20nM) (HMI0375, Sigma-Aldrich) and negative control miR (HMC0002, Sigma-Aldrich). MicroRNA isolation was accomplished with miRVANA isolation kit according to manufacturer instructions. cDNA synthesis was performed expression, respectively, and calibrated with Ct of controls. The real-time quantitative PCR (RT-qPCR) reaction was performed using the TaqMan Fast Advanced Master Mix (Thermo Sci.). Ct values of miR2110 were normalized to miR-186-5p and miR16-5p for the intracellular gene. Cell proliferation analysis was analyzed with the xCELLigence RTCA System. Wound healing assay was analyzed with the ImageJ program and relative fold change calculated. Results: The mimic-miR-2110 transfected SNU398 cells nearly nine-fold (log2) more miR-2110 expressed compared to negative control transfected cells. The mimic-miR-2110 transfected HCC cell proliferation significantly inhibited compared to the negative control cells. Furthermore, miR-2110-SNU398 cell migration capacity was relatively four-fold decreased compared to negative control-miR-SNU398 cells. Conclusion: Our results suggest the miR-2110 inhibited cell proliferation and also miR-2110 negatively affect cell migration compared to control groups in HCC cells. These data suggest the complexity of microRNA EMT transcription factors regulation. These initial results are pointed out the predictive biomarker capacity of miR-2110 in HCC.

Keywords: epithelial to mesenchymal transition, EMT, hepatocellular carcinoma cells, micro-RNA-2110, ZEB2

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Authors: Anushtha Saxena

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This paper examines the process of data monetisation bye-commerce companies operating in India. Data monetisation is collecting, storing, and analysing consumers’ data to use further the data that is generated for profits, revenue, etc. Data monetisation enables e-commerce companies to get better businesses opportunities, innovative products and services, a competitive edge over others to the consumers, and generate millions of revenues. This paper analyses the issues and challenges that are faced due to the process of data monetisation. Some of the issues highlighted in the paper pertain to the right to privacy, protection of data of e-commerce consumers. At the same time, data monetisation cannot be prohibited, but it can be regulated and monitored by stringent laws and regulations. The right to privacy isa fundamental right guaranteed to the citizens of India through Article 21 of The Constitution of India. The Supreme Court of India recognized the Right to Privacy as a fundamental right in the landmark judgment of Justice K.S. Puttaswamy (Retd) and Another v. Union of India . This paper highlights the legal issue of how e-commerce businesses violate individuals’ right to privacy by using the data collected, stored by them for economic gains and monetisation and protection of data. The researcher has mainly focused on e-commerce companies like online shopping websitesto analyse the legal issue of data monetisation. In the Internet of Things and the digital age, people have shifted to online shopping as it is convenient, easy, flexible, comfortable, time-consuming, etc. But at the same time, the e-commerce companies store the data of their consumers and use it by selling to the third party or generating more data from the data stored with them. This violatesindividuals’ right to privacy because the consumers do not know anything while giving their data online. Many times, data is collected without the consent of individuals also. Data can be structured, unstructured, etc., that is used by analytics to monetise. The Indian legislation like The Information Technology Act, 2000, etc., does not effectively protect the e-consumers concerning their data and how it is used by e-commerce businesses to monetise and generate revenues from that data. The paper also examines the draft Data Protection Bill, 2021, pending in the Parliament of India, and how this Bill can make a huge impact on data monetisation. This paper also aims to study the European Union General Data Protection Regulation and how this legislation can be helpful in the Indian scenarioconcerning e-commerce businesses with respect to data monetisation.

Keywords: data monetization, e-commerce companies, regulatory framework, GDPR

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Authors: Ana Lambelho

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Nowadays is very common that an activity may be performed independently or dependently. In Portugal, the Labour Law exclusively protects the dependent labour relations. The independent work is regulated by civil law, where the autonomy of the will is the main principle. For companies is more advantageous to hire people under a service agreement since, in that case, the relation is not submitted to the limits established in Labour law and collective bargaining. This practice has nothing wrong, if the performance of work is, in fact, made autonomously. The problem is the increased frequency of the celebration of service agreements to hide a legal relation of subordination. Aware of this and regarding the huge difficulty to demonstrate the existence of subordinated work (that often runs against the employee), the Portuguese legislator devoted some legislative rules in order to facilitate the evidence of legal subordination and, on the other hand, to avoid the misuse of the provision of service agreements. This study focuses precisely on the analysis of this solution, namely the so-called presumption of ‘laboralidade’ and on the lawsuit to recognize the existence of a labour contract. The presumption of the existence of a labour contract is present in the Portuguese legal system since 2003, and received, with the 2009 Labour Code, a new redaction that, according to the doctrine and the jurisprudence, finally approached it to a legal presumption, with the consequent reversal of the burden of proof and, in consequence, made easier to proof the legal subordination, because the employee will just have to plead and prove the existence of two of the elements described in the law to use this presumption. Another change in the Portuguese legal framework is related with the competencies of the Authority for Working Conditions (AWC): now, if during an inspection, the Authority finds a situation that seems to be an undeclared employment situation, it may access the company and, if it does not regularize voluntarily the situation, AWC has a duty to communicate to the public prosecutor, who will begin the lawsuit for the recognition of the existence of an employment contract. To defend the public interest, the action to recognize the existence of an employment contract will follow its terms, even against the employee will. Although the existence of these mechanisms does not solve by itself the problem of evasion of labour law and false ‘green receipts’, it is undeniable that it is an important step in combating fraud in this field.

Keywords: independent work, labour contract, Portugal, service agreement

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Authors: Elena Carcano, James Ball, Betty Tiko

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Carrying capacity refers to the maximum population that a given level of resources can sustain over a specific period. In undisturbed environments, the maximum population is determined by the availability and distribution of resources, as well as the competition for their utilization. This information is typically obtained through long-term data collection. In regulated environments, where resources are artificially modified, populations must adapt to changing conditions, which can lead to additional challenges due to fluctuations in resource availability over time and throughout development. An example of this is observed in hydropower plants, which alter water flow and impact fish migration patterns and behaviors. To assess how fish species can adapt to these changes, specialized surveys are conducted, which provide valuable information on fish populations, sample sizes, and density before and after flow modifications. In such situations, it is highly recommended to conduct hydrological and biological monitoring to gain insight into how flow reductions affect species adaptability and to prevent unfavorable exploitation conditions. This analysis involves several planned steps that help design appropriate hydropower production while simultaneously addressing environmental needs. Consequently, the study aims to strike a balance between technical assessment, biological requirements, and societal expectations. Beginning with a small hydro project that requires restoration, this analysis focuses on the lower tail of the Flow Duration Curve (FDC), where both hydrological and environmental goals can be met. The proposed approach involves determining the threshold condition that is tolerable for the most vulnerable species sampled (Telestes Muticellus) by identifying a low flow value from the long-term FDC. The results establish a practical connection between hydrological and environmental information and simplify the process by establishing a single reference flow value that represents the minimum environmental flow that should be maintained.

Keywords: carrying capacity, fish bypass ladder, long-term streamflow duration curve, eta-beta method, environmental flow

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Authors: Hilly Moodrick-Even Khen

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This study analyzes the legal regulation of the use of force in international law in the context of three emerging Palestinian forms of struggle against Israeli occupation: the Knife Intifada, Gaza border disturbances, and the launching of incendiary kites. It discusses what legal paradigms or concepts should regulate the type and level of force used in each situation—a question that is complicated by various dilemmas—and appraises the Israel Defence Forces policies tailored in response. Methodologically, the study is based on analysis of scholarship on the conceptual legal issues as well as dicta of the courts. It evaluates the applicability of two legal paradigms regulating the use of force in military operations—(i) the conduct of hostilities and (ii) law enforcement—as well as the concept of self-defense in international law and the escalation of force procedure. While the “Knife Intifada” clearly falls under the law enforcement paradigm, the disturbances at the border and the launching of incendiary kites raise more difficult questions, as applying law enforcement, especially in the latter case, can have undesirable ramifications for safeguarding humanitarian interests. The use of force in the cases of the border disturbances and the incendiary kites should thus be regulated, mutatis mutandis, by the concept of self-defense and escalation of force procedures; and in the latter case, the hostilities paradigm can also be applied. The study provides a factual description and analysis of the background and nature of the forms of struggle in Gaza and the West Bank—in each case surveying the geo-political developments since operation Protective Edge, contextualizing how the organized and unorganized violent activities evolved, and analyzing them in terms of level of organization and intensity. It then presents the two paradigms of the use of force—law enforcement and conduct of hostilities—and the concept of self-defense. Lastly, it uses the factual findings as the basis for legally analyzing which paradigm or concept regulating the use of force applies for each form of struggle. The study concludes that in most cases, the concept of self-defense is preferable to the hostilities or the law enforcement paradigms, as it best safeguards humanitarian interests and ensures the least loss of civilian lives.

Keywords: Israeli-Palestinian conflict, self defense, terrorism, use of force

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Authors: Islam Nowisser, Noha Farag, Mohamed El Azizi

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Helicobacter pylori is a highly important human pathogen which inhabits about 50% of the population worldwide. Infection with this bacteria is very hard to treat, with high probability of recurrence. H. pylori causes severe gastric diseases, including peptic ulcer, gastritis, and gastric cancer, which has been linked to chronic inflammation. The infection has been reported to be associated with high levels of pro-inflammatory cytokines, especially IL-1β and TNF-α. The aim of the current study is to investigate the molecular mechanisms by which H. pylori activates NLRP3 inflammasome and its contribution to Il-1 β production in an innate cellular model. H. pylori PMSS1 and G27 standard strains, as well as the PMSS1 isogenic mutant strain PMSS1ΔVacA and G27ΔVacA, G27ΔCagA in addition to clinical isolates obtained from biopsy samples from the antrum and corpus mucosa of chronic gastritis patients, were used to establish infection in RAW-264.7 macrophages. The production levels of TNF-α and IL-1β was assessed using ELISA. Since expression of these cytokines is often regulated by the transcription factor complex, nuclear factor-kB (NF-kB), the activation of NF-κB in H. pylori infected cells was also evaluated by luciferase assay. Genomic DNA was extracted from bacterial cultures of H. pylori clinical isolates as well as the standard strains and their corresponding mutants, where they were evaluated for the cagA pathogenicity island and vacA expression. The correlation between these findings and expression of the cagA Pathogenicity Island and vacA in the bacteria was also investigated. The results showed IL-1β, and TNF-α production significantly increased in raw macrophages following H. pylori infection. The cagA+ and vacA+ H. pylori strains induced significant production of IL-1β compared to cagA- and vacA- strains. The activation pattern of NF-κB was correlated in the isolates to their cagA and vacA expression profiles. A similar finding could not be confirmed for TNF-α production. Our study shows the ability of H. pylori to activate NF-kB and induce significant IL-1β production as a possible mechanism for the augmented inflammatory response seen in subjects infected with cagA+ and vacA+ H. pylori strains that would lead to the progression to more severe form of the disease.

Keywords: Helicobacter pylori, IL-1β, inflammatory cytokines, nuclear factor KB, TNF-α

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Authors: Misty Attwood, Helgi Schioth

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Transmembrane proteins are important components in many essential cell processes such as signal transduction, cell-cell signalling, transport of solutes, structural adhesion activities, and protein trafficking. Due to their involvement in diverse critical activities, transmembrane proteins are implicated in different disease pathways and hence are the focus of intense interest in understanding functional activities, their pathogenesis in disease, and their potential as pharmaceutical targets. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. In this in silico bioinformatics analysis, we identify and comprehensively characterize the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). We classify nearly 60 5TM proteins in which 31 are members of ten families that contain two or more family members and all members are predicted to contain the 5TM architecture. Furthermore, nine singlet proteins that contain the 5TM architecture without paralogues detected in humans were also identifying, indicating the evolution of single unique proteins with the 5TM structure. Interestingly, more than half of these proteins function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this family in sharp contrast with other TM families. Three major 5TM families were identified and include the Tweety family, which are pore-forming subunits of the swelling-dependent volume regulated anion channel in astrocytes; the sidoreflexin family that acts as mitochondrial amino acid transporters; and the Yip1 domain family engaged in vesicle budding and intra-Golgi transport. About 30% of the proteins have enhanced expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumour types, indicating further investigation into the function and expression of these proteins is important. This study provides the first comprehensive analysis of proteins with 5TM regions and provides details of the unique characteristics and application in pharmaceutical development.

Keywords: 5TM, cancer prognostic marker, drug targets, transmembrane protein

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Authors: Rayhana Begum, Manju Sharma

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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

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Authors: Shih-Ping Liu, Cheng-Hsuan Chang, Yu-Chuen Huang, Shih-Yin Chen, Woei-Cherng Shyu

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Embryonic stem cells (ES) and induced pluripotnet stem cells (iPS) are both pluripotent stem cells. For mouse stem cells culture technology, leukemia inhibitory factor (LIF) was used to maintain the pluripotency of stem cells in vitro. However, LIF is an expensive reagent. The goal of this study was to find out a pure compound extracted from Chinese herbal medicine that could maintain stem cells pluripotency to replace LIF and improve the iPS generation efficiency. From 20 candidates traditional Chinese medicine we found that Cordycepsmilitaris triggered the up-regulation of stem cells activating genes (Oct4 and Sox2) expression levels in MEF cells. Cordycepin, a major active component of Cordycepsmilitaris, also could up-regulate Oct4 and Sox2 gene expression. Furthermore, we used ES and iPS cells and treated them with different concentrations of Cordycepin (replaced LIF in the culture medium) to test whether it was useful to maintain the pluripotency. The results showed higher expression levels of several stem cells markers in 10 μM Cordycepin-treated ES and iPS cells compared to controls that did not contain LIF, including alkaline phosphatase, SSEA1, and Nanog. Embryonic body formation and differentiation confirmed that 10 μM Cordycepin-containing medium was capable to maintain stem cells pluripotency after four times passages. For mechanism analysis, microarray analysis indicated extracellular matrix and Jak/Stat signaling pathway as the top two deregulated pathways. In ECM pathway, we determined that the integrin αVβ5 expression levels and phosphorylated Src levels increased after Cordycepin treatment. In addition, the phosphorylated Jak2 and phosphorylated Sat3 protein levels were increased after Cordycepin treatment and suppressed with the Jak2 inhibitor, AG490. The expression of cytokines associated with Jak2/Stat3 signaling pathway were also up-regulated by Q-PCR and ELISA assay. Lastly, we used Oct4-GFP MEF cells to test iPS generation efficiency following Cordycepin treatment. We observed that 10 Μm Cordycepin significantly increased the iPS generation efficiency in day 21. In conclusion, we demonstrated Cordycepin could maintain the pluripotency of stem cells through both of ECM and Jak2/Stat3 signaling pathway and improved iPS generation efficiency.

Keywords: cordycepin, iPS cells, Jak2/Stat3 signaling pathway, molecular biology

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Authors: Moksha Singh

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The proponents of deinstitutionalization, including Goffman and others, in their works, have regarded institutions (orphanages to be specific) as regulated social arrangements that negatively impinge upon a resident’s development. They, therefore, propose alternative forms of care. However, even after five decades of this critique institutionalization remains the only hope for children with social, physical and mental disabilities in larger parts of the developing world such as the conflict affected state of Jammu and Kashmir in India. This paper is based on the experiences of children who lost their parents to insurgency and counter-insurgency operations and the rehabilitation process. This study is qualitative in nature and adopts descriptive-cum-exploratory research design. Using theoretical sampling, six orphanages and thirty one child residents who lost their parent(s) in the course of the armed conflict in the state of Jammu and Kashmir in India were studied in the year 2009-2010. It included interviews, observation, life histories and introspective accounts of the orphans and the management. The results were drawn through the qualitative examination, understanding, and interpretation of the primary and secondary data. The findings suggested that rehabilitation of these conflict-affected children is taking place mainly through residential child care facilities run by non-governmental bodies. Alternative forms of rehabilitation are not functional in the state because of various geopolitical and socio-cultural complexities. Even after five years of arriving at these conclusions and more, the state of Jammu and Kashmir still lacks a comprehensive rehabilitation plan for these children. This has further encouraged a mushroomed growth of legal and illegal institutions. Some of these institutions compromise the standard norms of functioning and yet remain the only hope for thousands rendered orphan. These institutions, therefore, are there to stay as other alternative forms of care are not available in the state. A comprehensive intervention policy is needed based on the cultural specifics of the state and incorporation of views of institutions offering aid, the state and the children. The paper introduces Small Group Residential Care Model through which it is expected that the restoration process can be made smooth and effective.

Keywords: armed conflict, children's rights, institutionalization, orphanages, rehabilitation

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Authors: Marriette Sakah, Christoph Kuhn, Samuel Gyamfi

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Global electricity demand of households in 2005 is estimated to double by 2025 and nearly double again in 2030. The residential sector promises considerable demand growth through infrastructural and equipment investments, the majority of which is projected to occur in developing countries. This lays bare the urgency for enhanced efficiency in all energy systems combined with exploitation of local potential for renewable energy systems. This study explores options for reducing energy consumption, particularly in residential buildings and providing robust, decentralized and renewable energy supply for African cities. The potential of energy efficiency measures and the potential of harnessing local resources for renewable energy supply are quantitatively assessed. The scale of research specifically addresses the city level, which is regulated by local authorities. Local authorities can actively promote the transition to a renewable-based energy supply system by promoting energy efficiency and the use of alternative renewable fuels in existing buildings, and particularly in planning and development of new settlement areas through the use of incentives, regulations, and demonstration projects. They can also support a more sustainable development by shaping local land use and development patterns in such ways that reduce per capita energy consumption and are benign to the environment. The subject of the current case study, Tema, is Ghana´s main industrial hub, a port city and home to 77,000 families. Residential buildings in Tema consumed 112 GWh of electricity in 2013 or 1.45 MWh per household. If average household electricity demand were to decline at an annual rate of just 2 %, by 2035 Tema would consume only 134 GWh of electricity despite an expected increase in the number of households by 84 %. The work is based on a ground survey of the city’s residential sector. The results show that efficient technologies and decentralized renewable energy systems have great potential for meeting the rapidly growing energy demand of cities in developing countries.

Keywords: energy efficiency, energy saving potential, renewable energy integration, residential buildings, urban Africa

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

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

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

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