Search results for: mandatory regulation

Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

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Authors: Kiseob Chung, Hyeonmin Kang

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This study aims to explore what is intercultural competency needed for teacher through their experience at the public multicultural alternative school. The public alternative multicultural school is an accredited school for immigrants or students from multicultural families who have experienced school maladjustment at public school. This school has self-regulation in curriculum and function of bridge to public school by helping their adaptation. In particular, this study answers the following questions: What are the most difficulties for teacher at the multicultural alternative school in comparison to public school? What competencies are required for teacher at the multicultural alternative school? Which competencies in cognitive, emotional and practical area should be more required in order for teacher to communicate with student effectively (successfully) in class and other activities in school? What is the background of that we called these competencies especially as ‘intercultural’? This study focuses to clarify teacher’s competency to help immigrants of students from multicultural background to adjust to school life with the term of intercultural competency.

Keywords: intercultural competency for teacher, multicultural alternative school, multicultural students, school maladjustment

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Authors: Avan Al-Saffar, Eun-Jin Kim

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Both the logistic growth model and the gompertz growth model are used to describe growth processes. Both models driven by perturbations in different cases are investigated using information theory as a useful measure of sustainability and the variability. Specifically, we study the effect of different oscillatory modulations in the system's parameters on the evolution of the system and Probability Density Function (PDF). We show the maintenance of the initial conditions for a long time. We offer Fisher information analysis in positive and/or negative feedback and explain its implications for the sustainability of population dynamics. We also display a finite amplitude solution due to the purely fluctuating growth rate whereas the periodic fluctuations in negative feedback can lead to break down the system's self-regulation with an exponentially growing solution. In the cases tested, the gompertz and logistic systems show similar behaviour in terms of information and sustainability although they develop differently in time.

Keywords: dynamical systems, fisher information, probability density function (pdf), sustainability

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Authors: Angkrit Phitchayangkoon, Ar-Aishah Dadeh

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Background: A key aim of triage is to identify the patients with high risk of cardiac arrest because they require intensive monitoring, resuscitation facilities, and early intervention. We aimed to identify the predicting factors such as initial vital signs, serum pH, serum lactate level, initial capillary blood glucose, and Modified Early Warning Score (MEWS) which affect the occurrence of cardiac arrest in an emergency department (ED). Methods: We conducted a retrospective data review of ED patients in an emergency department (ED) from 1 August 2014 to 31 July 2016. Significant variables in univariate analysis were used to create a multivariate analysis. Differentiation of predicting factors between cardiac arrest patient and non-cardiac arrest patients for occurrence of cardiac arrest in an emergency department (ED) was the primary outcome. Results: The data of 527 non-trauma patients with Emergency Severity Index (ESI) 1-3 were collected. The factors found to have a significant association (P < 0.05) in the non-cardiac arrest group versus the cardiac arrest group at the ED were systolic BP (mean [IQR] 135 [114,158] vs 120 [90,140] mmHg), oxygen saturation (mean [IQR] 97 [89,98] vs 82.5 [78,95]%), GCS (mean [IQR] 15 [15,15] vs 11.5 [8.815]), normal sinus rhythm (mean 59.8 vs 30%), sinus tachycardia (mean 46.7 vs 21.7%), pH (mean [IQR] 7.4 [7.3,7.4] vs 7.2 [7,7.3]), serum lactate (mean [IQR] 2 [1.1,4.2] vs 7 [5,10.8]), and MEWS score (mean [IQR] 3 [2,5] vs 5 [3,6]). A multivariate analysis was then performed. After adjusting for multiple factors, ESI level 2 patients were more likely to have cardiac arrest in the ER compared with ESI 1 (odds ratio [OR], 1.66; P < 0.001). Furthermore, ESI 2 patients were more likely than ESI 1 patients to have cardiovascular disease (OR, 1.89; P = 0.01), heart rate < 55 (OR, 6.83; P = 0.18), SBP < 90 (OR, 3.41; P = 0.006), SpO2 < 94 (OR, 4.76; P = 0.012), sinus tachycardia (OR, 4.32; P = 0.002), lactate > 4 (OR, 10.66; P = < 0.001), and MEWS > 4 (OR, 4.86; P = 0.028). These factors remained predictive of cardiac arrest at the ED. Conclusion: The factors related to cardiac arrest in the ED are ESI 1 patients, ESI 2 patients, patients diagnosed with cardiovascular disease, SpO2 < 94, lactate > 4, and a MEWS > 4. These factors can be used as markers in the event of simultaneous arrival of many patients and can help as a pre-state for patients who have a tendency to develop cardiac arrest. The hemodynamic status and vital signs of these patients should be closely monitored. Early detection of potentially critical conditions to prevent critical medical intervention is mandatory.

Keywords: cardiac arrest, predicting factor, emergency department, emergency patient

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Authors: Yiqi Wu, Simon Tait, Andrew Nichols

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Management of UK railway drainage assets is challenging due to the large amounts of historical assets with long asset life cycles. A major concern for asset managers is to maintain the required performance economically and efficiently while complying with the relevant regulation and legislation. As the majority of the drainage assets are buried underground and are often difficult or costly to examine, it is important for asset managers to understand and model the degradation process in order to foresee the upcoming reduction in asset performance and conduct proactive maintenance accordingly. In this research, a Markov chain approach is used to model the deterioration process of rail drainage assets. The study is based on historical condition scores and characteristics of drainage assets across the whole railway network in England, Scotland, and Wales. The model is used to examine the effect of various characteristics on the probabilities of degradation, for example, the regional difference in probabilities of degradation, and how material and shape can influence the deterioration process for chambers, channels, and pipes.

Keywords: deterioration, degradation, markov models, probability, railway drainage

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Authors: Sulasmi Sudirman, Rachmadanty Mujah Hartika

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Traffic violence is currently a big issue in Indonesia. However, the road users perceived risk that is caused by traffic violence is low. The lack of safety driving awareness is one of the factors that road users committed to traffic violence. There are several lists of common traffic violence in Indonesia such as lack of physical fitness, not wearing helmet, unfasten seatbelt, breaking through the traffic light, not holding a driving license, and some more violence. This research sought to explore the perception of road users toward traffic violence. The participants were road users in Makassar, Indonesia who were using cars and motorbikes. The method of the research was a qualitative approach by using a personal interview to collect data. The research showed that there three main ideas of perceiving traffic violence which are motives, environment that supported traffic violence, and reinforcement. The road users committed traffic violence had particular motive, for example, rushing. The road users committed to traffic violence when other road users and significant other did the same. The road users committed traffic violence when the police were not there to give a ticket. It can be concluded that the perception of road users toward traffic violence determined by internal aspect, the social aspect, and regulation.

Keywords: perception, road users, traffic, violence

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Authors: Sanguk Nam, Van Ha Nguyen, Hanjung Song

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For low-power applications such as adapters for portable devices and USB chargers, the primary side regulation (PSR) fly-back converter is widely used in lieu of the conventional fly-back converter using opto-coupler because of its simpler structure and lower cost. In the literature, there has been studies focusing on the design of PSR circuit; however, the conventional sensing method in PSR circuit using RC delay has a lower accuracy as compared to the conventional fly-back converter using opto-coupler. In this paper, we propose a novel PWM/PFM controller using new sensing technique for the PSR fly-back converter which can control an accurate output voltage. The conventional PSR circuit can sense the output voltage information from the auxiliary winding to regulate the duty cycle of the clock that control the output voltage. In the sensing signal waveform, there has two transient points at time the voltage equals to Vout+VD and Vout, respectively. In other to sense the output voltage, the PSR circuit must detect the time at which the current of the diode at the output equals to zero. In the conventional PSR flyback-converter, the sensing signal at this time has a non-sharp-negative slope that might cause a difficulty in detecting the output voltage information since a delay of sensing signal or switching clock may exist which brings out an unstable operation of PSR fly-back converter. In this paper instead of detecting output voltage at a non-sharp-negative slope, a sharp-positive slope is used to sense the proper information of the output voltage. The proposed PRS circuit consists of a saw-tooth generator, a summing circuit, a sample and hold circuit and a peak detector. Besides, there is also the start-up circuit which protects the chip from high surge current when the converter is turned on. Additionally, to reduce the standby power loss, a second mode which operates in a low frequency is designed beside the main mode at high frequency. In general, the operation of the proposed PSR circuit can be summarized as following: At the time the output information is sensed from the auxiliary winding, a saw-tooth signal from the saw-tooth generator is generated. Then, both of these signals are summed using a summing circuit. After this process, the slope of the peak of the sensing signal at the time diode current is zero becomes positive and sharp that make the peak easy to detect. The output of the summing circuit then is fed into a peak detector and the sample and hold circuit; hence, the output voltage can be properly sensed. By this way, we can sense more accurate output voltage information and extend margin even circuit is delayed or even there is the existence of noise by using only a simple circuit structure as compared with conventional circuits while the performance can be sufficiently enhanced. Circuit verification was carried out using 0.35μm 700V Magnachip process. The simulation result of sensing signal shows a maximum error of 5mV under various load and line conditions which means the operation of the converter is stable. As compared to the conventional circuit, we achieved very small error only used analog circuits compare with conventional circuits. In this paper, a PWM/PFM controller using a simple and effective sensing method for PSR fly-back converter has been presented in this paper. The circuit structure is simple as compared with the conventional designs. The gained results from simulation confirmed the idea of the design

Keywords: primary side regulation, PSR, sensing technique, peak detector, PWM/PFM control, fly-back converter

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Authors: Mahmoud Said Jneid, Péter Harth

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EVs with independent wheel driving greatly improve vehicle stability in poor road conditions. Wheel torques can be precisely controlled through electric motors driven using advanced technologies. As a result, various types of advanced chassis assistance systems (ACAS) can be implemented. This paper proposes an integrated torque vectoring control based on wheel slip regulation in both braking and traction modes. For generating the corrective yaw moment, the vehicle yaw rate and sideslip angle are monitored. The corrective yaw moment is distributed into traction and braking torques based on an equal-opposite components approach. The proposed torque vectoring control scheme is validated in simulation and the results show its superiority when compared to conventional schemes.

Keywords: all-wheel-drive, electric vehicle, torque vectoring, regenerative braking, stability control, traction control, yaw rate control

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Authors: Robby Dwiko Juliardi, Queena K. Qian

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Economic, environmental, and human considerations, as sustainable building design principles, are to be balanced and integrated into building design strategy. Building codes often suggest the efficient and sustainable building products, such as energy-efficient fixtures. However, building departments sometimes fail to manage the full range of requirements in the building assessment, such as siting, neighborhood proximity, and public facility, etc. Hence, it shows roadmap develops the future, an extended look at the future of a chosen field of inquiry composed from the collective knowledge and imagination of the brightest drivers of change in that field. This paper is taken from the best practice of green building implementation in a few countries of Asia (China, Malaysia, and India). Sustainable development will be presented on developing the roadmap of sustainability development of a country. Findings on the similarities and dissimilarities of those countries will show: (1) A general knowledge development on the sustainable green roadmap in Asia, (2) What are the components of developing the roadmap, and (3) What affects the government regulation in a political ecology.

Keywords: developing roadmap, green building, political ecology, sustainable development

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Authors: Pavel Borodkin, Nikolay Khrennikov, Azamat Gazetdinov

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The problem of ensuring of VVER type reactor equipment integrity is now most actual in connection with justification of safety of the NPP Units and extension of their service life to 60 years and more. First of all, it concerns old units with VVER-440 and VVER-1000. The justification of the VVER equipment integrity depends on the reliability of estimation of the degree of the equipment damage. One of the mandatory requirements, providing the reliability of such estimation, and also evaluation of VVER equipment lifetime, is the monitoring of equipment radiation loading parameters. In this connection, there is a problem of justification of such normative parameters, used for an estimation of the pressure vessel metal embrittlement, as the fluence and fluence rate (FR) of fast neutrons above 0.5 MeV. From the point of view of regulatory practice, a comparison of displacement per atom (DPA) and fast neutron fluence (FNF) above 0.5 MeV has a practical concern. In accordance with the Russian regulatory rules, neutron fluence F(E > 0.5 MeV) is a radiation exposure parameter used in steel embrittlement prediction under neutron irradiation. However, the DPA parameter is a more physically legitimate quantity of neutron damage of Fe based materials. If DPA distribution in reactor structures is more conservative as neutron fluence, this case should attract the attention of the regulatory authority. The purpose of this work was to show what radiation load parameters (fluence, DPA) on all VVER equipment should be under control, and give the reasonable estimations of such parameters in the volume of all equipment. The second task is to give the conservative estimation of each parameter including its uncertainty. Results of recently received investigations allow to test the conservatism of calculational predictions, and, as it has been shown in the paper, combination of ex-vessel measured data with calculated ones allows to assess unpredicted uncertainties which are results of specific unique features of individual equipment for VVER reactor. Some results of calculational-experimental investigations are presented in this paper.

Keywords: equipment integrity, fluence, displacement per atom, nuclear power plant, neutron activation measurements, neutron transport calculations

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Authors: Alan Vaško, Juraj Belan, Lenka Hurtalová, Eva Tillová

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The aim of this study is to evaluate the influence of raw material composition on the microstructure, mechanical and fatigue properties and micromechanisms of failure of nodular cast iron. In order to evaluate the influence of charge composition, the structural analysis, mechanical and fatigue tests and micro fractographic analysis were carried out on specimens of ten melts with different charge compositions. The basic charge of individual melts was formed by a different ratio of pig iron and steel scrap and by different additive for regulation of chemical composition (silicon carbide or ferrosilicon). The results show differences in mechanical and fatigue properties, which are connected with the microstructure. SiC additive positively influences microstructure. Consequently, mechanical and fatigue properties of nodular cast iron are improved, especially in the melts with the higher ratio of steel scrap in the charge.

Keywords: nodular cast iron, silicon carbide, microstructure, mechanical properties

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Authors: Zakir Husain

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Main objective of a power transformer design optimization problem requires minimizing the total overall cost and/or mass of the winding and core material by satisfying all possible constraints obligatory by the standards and transformer user requirement. The constraints include appropriate limits on winding fill factor, temperature rise, efficiency, no-load current and voltage regulation. The design optimizations tasks are a constrained minimum cost and/or mass solution by optimally setting the parameters, geometry and require magnetic properties of the transformer. In this paper, present the above design problems have been formulated by using genetic algorithm (GA) and simulated annealing (SA) on the MATLAB platform. The importance of the presented approach is stems for two main features. First, proposed technique provides reliable and efficient solution for the problem of design optimization with several variables. Second, it guaranteed to obtained solution is global optimum. This paper includes a demonstration of the application of the genetic programming GP technique to transformer design.

Keywords: optimization, power transformer, genetic algorithm (GA), simulated annealing technique (SA)

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Authors: Nisha Sharma, Mili Kaur, Ashutosh Halder, Seema Kaushal, Manoj Kumar, Manish Jain

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Purpose: To investigate microRNAs (miRNA) as an epigenomic etiological factor in idiopathic non-obstructive azoospermia (NOA). In order to achieve the same, an association was seen between occupational exposure to radiation, thermal, and chemical factors and idiopathic cases of non-obstructive azoospermia, and later, testicular differential miRNA expression profiling was done in exposure group NOA cases. Method: It is a prospective study in which 200 apparent idiopathic male factor infertility cases, who have been advised to undergo testicular fine needle aspiration (FNA) evaluation, are recruited. A detailed occupational history was taken to understand the possible type of exposure due to the nature and duration of work. A total of 26 patients were excluded upon XY-FISH and Yq microdeletion tests due to the presence of genetic causes of infertility, 6 hypospermatogeneis (HS), six Sertoli cell-only syndrome (SCOS), and six normospermatogeneis patients testicular FNA samples were used for RNA isolation followed by small RNA sequencing and nCounter miRNA expression analysis. Differential miRNA expression profile of HS and SCOS patients was done. A web-based tool, miRNet, was used to predict the interacting compounds or chemicals using the shortlisted miRNAs with high fold change. The major limitation encountered in this study was the insufficient quantity of testicular FNA sample used for total RNA isolation, which resulted in a low yield and RNA integrity number (RIN) value. Therefore, the number of RNA samples admissible for differential miRNA expression analysis was very small in comparison to the total number of patients recruited. Results: Differential expression analysis revealed 69 down-regulated and 40 up-regulated miRNAs in HS and 66 down-regulated and 33 up-regulated miRNAs in SCOS in comparison to normospermatogenesis controls. The miRNA interaction analysis using the miRNet tool showed that the differential expression profiles of HS and SCOS patients were associated with arsenic trioxide, bisphenol-A, calcium sulphate, lithium, and cadmium. These compounds are reproductive toxins and might be responsible for miRNA-mediated epigenetic deregulation leading to NOA. The association between occupational risk factor exposure and the non-exposure group of NOA patients was not statistically significant, with ꭓ2 (3, N= 178) = 6.70, p= 0.082. The association between individual exposure groups (radiation, thermal, and chemical) and various sub-types of NOA is also not significant, with ꭓ2 (9, N= 178) = 15.06, p= 0.089. Functional analysis of HS and SCOS patients' miRNA profiles revealed some important miR-family members in terms of male fertility. The miR-181 family plays a role in the differentiation of spermatogonia and spermatocytes, as well as the transcriptional regulation of haploid germ cells. The miR-34 family is expressed in spermatocytes and round spermatids and is involved in the regulation of SSCs differentiation. Conclusion: The reproductive toxins might adopt the miRNA-mediated mechanism of disease development in idiopathic cases of NOA. Chemical compound induced; miRNA-mediated epigenetic deregulation can give a future perspective on the etiopathogenesis of the disease.

Keywords: microRNA, non-obstructive azoospermia (NOA), occupational exposure, hypospermatogenesis (HS), Sertoli cell only syndrome (SCOS)

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Authors: Simin Sadeghi-Saeb

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Metacognitive strategies consistently play important roles in reading comprehension. The metacognitive strategies involve the active monitoring and consequent regulation and orchestration of the cognitive processes in relation to the cognitive objects or data on which they bear. In this paper, the effect of instruction in using metacognitive strategies on reading academic materials, type of metacognitive strategies were mostly used by college university students before and after the instruction and the level they use those strategies before and after the instruction were studied. For these aims, 50 female college students were chosen. Then, they were divided randomly into two groups, experimental and control groups. At first session, students in both groups took the standard TOFEL exam. After the pre-test had been administered, the instruction began. After treatment, a post-test was taken. It is useful to state that after pre-test and post-test the same questionnaire was handed to the students of experimental group. The results of this research show that the instruction of metacognitive strategies has positive effect on the students' scores in reading comprehension tests. Furthermore, it showed that before and after the instruction, the students' usage of metacognitive strategies changed. Also, it demonstrated that the instruction affected the students' level of metacognitive strategies' usage.

Keywords: EFL students, English reading comprehension, instruction, metacognitive strategies

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Authors: Elmira Aliyeva, Dadash Huseynov, Robert Hoogendoorn, Salomon Kroonenberg

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The Kura River is the major water artery in the Southern Caucasus; it is a third river in the Caspian Sea basin in terms of length and size of the catchment area, the second in terms of the water budget, and the first in the volume of sediment load. Understanding of major controls on the Kura fluvial- deltaic system is valuable for efficient management of the highly populated river basin and coastal zone. We have studied grain size of sediments accumulated in the river channels and delta and dated by 210Pb method, astrophotographs, old topographic and geological maps, and archive data. At present time sediments are supplied by the Kura River to the Caspian Sea through three distributary channels oriented north-east, south-east, and south-west. The river is dominated by the suspended load - mud, silt, very fine sand. Coarse sediments are accumulated in the distributaries, levees, point bar, and delta front. The annual suspended sediment budget in the time period 1934-1952 before construction of the Mingechavir water reservoir in 1953 in the Kura River midstream area was 36 mln.t/yr. From 1953 to 1964, the suspended load has dropped to 12 mln.t/yr. After regulation of the Kura River discharge the volume of suspended load transported via north-eastern channel reduced from 35% of the total sediment amount to 4%, and through the main south-eastern channel increased from 65% to 96% with further fall to 56% due to creation of new south-western channel in 1964. Between 1967-1976 the annual sediment budget of the Kura River reached 22,5 mln. t/yr. From 1977 to 1986, the sediment load carried by the Kura River dropped to 17,6 mln.t/yr. The historical data show that between 1860 and 1907, during relatively stable Caspian Sea level two channels - N and SE, appear to have distributed an equal amount of sediments as seen from the bilateral geometry of the delta. In the time period 1907-1929, two new channels - E and NE, appeared. The growth of three delta lobes - N, NE, and SE, and rapid progradation of the delta has occurred on the background of the Caspian Sea level rise as a result of very high sediment supply. Since 1929 the Caspian Sea level decline was followed by the progradation of the delta occurring along the SE channel. The eastern and northern channels have been silted up. The slow rate of progradation at its initial stage was caused by the artificial reduction in the sediment budget. However, the continuous sea-level fall has brought to this river bed gradient increase, high erosional rate, increase in the sediment supply, and more rapid progradation. During the subsequent sea-level rise after 1977 accompanied by the decrease in the sediment budget, the southern part of the delta has turned into a complex of small, shallow channels oriented to the south. The data demonstrate that behaviour of the Kura fluvial – deltaic system and variations in the sediment budget besides anthropogenic regulation are strongly governed by the Caspian Sea level very rapid changes.

Keywords: anthropogenic control on sediment budget, Caspian sea-level variations, Kura river sediment load, morphology of the Kura river delta, sedimentation in the Kura river delta

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Authors: Maria Casoria

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Throughout the last decade developing countries have been undergoing substantial reforms to promote the establishment of competition regimes, as consequence of the trade liberalization and the spread of a ‘competition awareness movement’ across the globe. The legislative trend affected the whole Asia. Notwithstanding the existence of extensive joint ventures, cartels and other collusive business relationships in this geographical area, almost all the countries have already passed or are committed to enforce specific laws in the field. The study dwells into legal solutions adopted in the five sub-regions in which the continent is commonly divided –i.e. Central, East, South, Southeast, and Western Asia- and, using a comparative methodology, shed lights on the main differences and similarities in place. The final outcome of the analysis is that, despite the undeniable divergences of approach, what links together the legislation in force in the region is the unveiled influence exercised by the European Union competition regulation. Consequently, in order to properly evaluate the deterrence of the rule of law in the sector concerned, it is fundamental to scrutinize the major role played by the EU and its policy for the evolution of pro-competitive practices in the continent.

Keywords: Asia, competition law, differences and similarities, European union, influences

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Authors: Vrushali Guhe, Shailza Singh

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Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

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Authors: Alexandra P. Alexandropoulou, Andreas Fousteris, Eleni Didaskalou, Dimitrios A. Georgakellos

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As urbanization is becoming a major stress factor not only for the urban environment but also for the wellbeing of city dwellers, incorporating the issues of urban health in strategic city planning and policy-making has never been more relevant. The impact of urbanization can vary from low to severe and relates to all non-communicable diseases caused by the different functions of cities. Air pollution, noise pollution, water and soil pollution, availability of open green spaces, and urban heat island are the major factors that can compromise citizens' health. Urban health describes the effects of the social environment, the physical environment, and the availability and accessibility to health and social services. To assess the quality of urban wellbeing, all urban characteristics that might have an effect on citizens' health must be considered, evaluated, and introduced in integrated local planning. A series of indices and indicators can be used to better describe these effects and set the target values in policy making. Local strategic planning is one of the most valuable development tools a local city administration can possess; thus, it has become mandatory under Greek law for all municipalities. It involves a two-stage procedure; the first aims to collect, analyse and evaluate data on the current situation of the city (administrative data, population data, environmental data, social data, swot analysis), while the second aims to introduce a policy vision described and supported by distinct (nevertheless integrated) actions, plans and measures to be implemented with the aim of city development and citizen wellbeing. In this procedure, the element of health is often neglected or under-evaluated. A relative survey was conducted among all Greek local authorities in order to shed light on the current situation. Evidence shows that the rate of incorporation of health in strategic planning is lacking behind. The survey also highlights key hindrances and concerns raised by local officials and suggests a path for the way forward.

Keywords: urban health, strategic planning, local authorities, integrated development

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Authors: Ryeong-Hyeon Kim, Ah-Reum Lee, Seong-Soo Roh, Gyo-Nam Kim

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Appropriate regulation of melanogenesis is important for the management of skin pigmentation-related disease. Although several beneficial effects of fisetin (3,7,3’,4’-tetrahydroxyflavone) have been reported, the precise role and molecular mechanisms of fisetin in skin health both remain unclear. Here, we induced melanogenesis of HRM2 mice (n=7/group) by UVB irradiation for 20 days. UVB-induced HRM2 mice showed that the significantly increased melanin accumulation, however, fisetin treatment (25mg and 50mg/kg of body weight) dose-dependently and significantly inhibits UVB-induced melanogenesis. In line with this, fisetin treatment effectively down-regulated m RNA and expression levels of tyrosinase, TRP2, and MITF. In addition, our inhibitor assay revealed the down-regulated melanogenic marker genes by fisetin treatment were mediated with connective tissue growth factor (CCN2)/TGF-β signaling pathway. Useful information is provided for development of functional foods using fisetin for skin health.

Keywords: connective tissue growth factor, fisetin, melanogenesis, skin, TGF-beta

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Authors: Sultana Afrin Nipa

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Life on Earth cannot thrive or survive without water. Water is intimately tied with community, culture, spirituality, identity, socio-economic progress, security, self-determination, and livelihood. Thus, access to water is a United Nations recognized human right due to its significance in these realms. However, there is often conflict between those who consider water as the spiritual and cultural value and those who consider it an economic value thus being threatened by economic development, corporate exploitation, government regulation, and increased privatization, highlighting the complex relationship between water and culture. The Colorado River basin is home to over 29 federally recognized tribal nations. To these tribes, it holds cultural, economic, and spiritual significance and often extends to deep human-to-non-human connections frequently precluded by the Westphalian regulations and settler laws. Despite the recognition of access to rivers as a fundamental human right by the United Nations, tribal communities and their water rights have been historically disregarded through inter alia, colonization, and dispossession of their resources. Law of the River such as ‘Winter’s Doctrine’, ‘Bureau of Reclamation (BOR)’ and ‘Colorado River Compact’ have shaped the water governance among the shareholders. However, tribal communities have been systematically excluded from these key agreements. While the Winter’s Doctrine acknowledged that tribes have the right to withdraw water from the rivers that pass through their reservations for self-sufficiency, the establishment of the BOR led to the construction of dams without tribal consultation, denying the ‘Winters’ regulation and violating these rights. The Colorado River Compact, which granted only 20% of the water to the tribes, diminishes the significance of international legal frameworks that prioritize indigenous self-determination and free pursuit of socio-economic and cultural development. Denial of this basic water right is the denial of the ‘recognition’ of their sovereignty and self-determination that questions the effectiveness of the international law. This review assesses the international legal frameworks concerning indigenous rights and water justice and aims to pinpoint gaps hindering the effective recognition and protection of Indigenous water rights in Colorado River Basin. This study draws on a combination of historical and qualitative data sets. The historical data encompasses the case settlements provided by the Bureau of Reclamation (BOR) respectively the notable cases of Native American water rights settlements on lower Colorado basin related to Arizona from 1979-2008. This material serves to substantiate the context of promises made to the Indigenous people and establishes connections between existing entities. The qualitative data consists of the observation of recorded meetings of the Central Arizona Project (CAP) to evaluate how the previously made promises are reflected now. The study finds a significant inconsistency in participation in the decision-making process and the lack of representation of Native American tribes in water resource management discussions. It highlights the ongoing challenges faced by the indigenous people to achieve their self-determination goal despite the legal arrangements.

Keywords: colorado river, indigenous rights, law of the river, water governance, water justice

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Authors: Jer-Yuh Liu, Je-Chiuan Ye, Jin-Ming Hwang

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Protein kinase C alpha (PKCα) is a key signaling molecule in human cancer development. As a therapeutic strategy, targeting PKCα is difficult because the molecule is ubiquitously expressed in non-malignant cells. PKCα is regulated by the cooperative interaction of the transcription factors myeloid zinc finger 1 (MZF-1) and Ets-like protein-1 (Elk-1) in human cancer cells. By conducting tissue array analysis, herein, we determined the protein expression of MZF-1/Elk-1/PKCα in various cancers. The data show that the expression of MZF-1/Elk-1 is correlated with that of PKCα in hepatocellular carcinoma (HCC), but not in bladder and lung cancers. In addition, the PKCα down-regulation by shRNA Elk-1 was only observed in the HCC SK-Hep-1 cells. Blocking the interaction between MZF-1 and Elk-1 through the transfection of their binding domain MZF-160–72 decreased PKCα expression. This step ultimately depressed the epithelial-mesenchymal transition potential of the HCC cells. These findings could be used to develop an alternative therapeutic strategy for patients with the PKCα-derived HCC.

Keywords: protein kinase C alpha, myeloid zinc finger 1, ets-like protein-1, hepatocellular carcinoma

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Authors: Ho Wen Hui, Azwina Wati Abdull Manaf, Asfarina Kartika Mohd Shakri

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The global trend of Fintech had taken the Malaysian shore by storm in recent years, thus making the studies and observations of its impacts more critical than ever. Additionally, Fintech has grown to become an unavoidable subject in the Islamic Banking and Finance (IBF) industry. In relation to that, this paper seeks to analyze the development of Fintech parallel with the IBF industry and its connection to Islamic economics. While the scarcity of studies on this area is apparent, it is found that there is a need to regulate the development of the Fintech Industry and its effects while analyzing the ramifications and positive effects of Fintech towards parties involved in IBF industry. This paper objectively studies the phenomenon of Islamic Fintech around the world as a whole as well as more specifically in Malaysia. The paper will then explore on the existing regulatory instruments in Malaysia, study their boundaries as well as limitations and contribute on possible reform to regulate Islamic Fintech in this jurisdiction. It is aimed that this paper will prompt and encourage more thorough studies to be conducted on the topic of Fintech which would subsequently contribute to a positive growth of the IBF industry worldwide.

Keywords: financial technology, FinTech, Islamic banking & finance, regulation

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Authors: Habib Aghdam Shahryar

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The aim of the present study was investigation on the effect of intraperipheral (IP) injection of ghrelin on serum insulin and glucose levels in native turkey. Seventy-two 28 day (d)-old native turkey were assigned into three treatments and four replicate for 40 days experimental rearing period: group 1, intact without any injection, group 2, injected 50 ng ghrelin/kg body weight (BW), and group 3, injected 100 ng ghrelin/kg BW. Intraperitoneal injection of rat ghrelin was conducted on d 28 and before the onset of the experimental rearing period. Blood samples were taken 12 hr after injection and 40 days after injection. The result showed glucose concentrations have been affected by administered ghrelin and significant between groups (P<0.01). Injection of ghrelin at G 100 increased glucose level of serum in 12 hr after injection and 40 days after injection (276.6 and 260.0 mg/dl, respectively). Also, by increasing the dose of injected ghrelin, insulin levels than the control group showed an increase (P < 0.001). This study suggests roles of ghrelin in serum biochemical regulation may show a different effect of ghrelin on blood parameters in avian species.

Keywords: ghrelin injection, insulin, glucose, turkey

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Authors: Priyanka Jain, Ashish K. Sharma, Esha Shukla, K. J. Mukherjee

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We propose a paradigm shift in our approach to design improved platforms for recombinant protein production, by addressing system level issues rather than the individual steps associated with recombinant protein synthesis like transcription, translation, etc. We demonstrate that by controlling and modulating the cellular stress response (CSR), which is responsible for feedback control of protein synthesis, we can generate hyper-producing strains. We did transcriptomic profiling of post-induction cultures, expressing different types of protein, to analyze the nature of this cellular stress response. We found significant down-regulation of substrate utilization, translation, and energy metabolism genes due to generation CSR inside the host cell. However, transcription profiling has also shown that many genes are up-regulated post induction and their role in modulating the CSR is unclear. We hypothesized that these up-regulated genes trigger signaling pathways, generating the CSR and concomitantly reduce the recombinant protein yield. To test this hypothesis, we knocked out the up-regulated genes, which did not have any downstream regulatees, and analyzed their impact on cellular health and recombinant protein expression. Two model proteins i.e., GFP and L-Asparaginase were chosen for this analysis. We observed a significant improvement in expression levels, with some knock-outs showing more than 7-fold higher expression compared to control. The 10 best single knock-outs were chosen to make 45 combinations of all possible double knock-outs. A further increase in expression was observed in some of these double knock- outs with GFP levels being highest in a double knock-out ΔyhbC + ΔelaA. However, for L-Asparaginase which is a secretory protein, the best results were obtained using a combination of ΔelaA+ΔcysW knock-outs. We then tested all the knock outs for their ability to enhance the expression of a 'difficult-to-express' protein. The Rubella virus E1 protein was chosen and tagged with sfGFP at the C-terminal using a linker peptide for easy online monitoring of expression of this fusion protein. Interestingly, the highest increase in Rubella-sGFP levels was obtained in the same double knock-out ΔelaA + ΔcysW (5.6 fold increase in expression yield compared to the control) which gave the highest expression for L-Asparaginase. However, for sfGFP alone, the ΔyhbC+ΔmarR knock-out gave the highest level of expression. These results indicate that there is a fair degree of commonality in the nature of the CSR generated by the induction of different proteins. Transcriptomic profiling of the double knock out showed that many genes associated with the translational machinery and energy biosynthesis did not get down-regulated post induction, unlike the control where these genes were significantly down-regulated. This confirmed our hypothesis of these genes playing an important role in the generation of the CSR and allowed us to design a strategy for making better expression hosts by simply knocking out key genes. This strategy is radically superior to the previous approach of individually up-regulating critical genes since it blocks the mounting of the CSR thus preventing the down-regulation of a very large number of genes responsible for sustaining the flux through the recombinant protein production pathway.

Keywords: cellular stress response, GFP, knock-outs, up-regulated genes

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Authors: Ibrahim Masud, Yusheng Kong, Adam Diyawu Rahman

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Mobile payment variously referred to as mobile money, mobile money transfer, and mobile wallet refers to payment services operated under financial regulation and performed from or via a mobile device. Mobile payment systems have come to augment and to some extent try to replace the conventional payment methods like cash, cheque, or credit cards. This study examines mobile payment adoption factors among retailers in Ghana. A conceptual framework was adopted from the extant literature using the Technology Acceptance Model and the Theory of Reasoned action as the theoretical bases. Data for the study was obtained from a sample of 240 respondents through a structured questionnaire. The PLS-SEM was used to analyze the data through SPSS v.22 and SmartPLS v.3. The findings indicate that factors such as perceived usefulness, perceived ease of use, perceived security, competitive pressure and facilitating conditions are the main determinants of mobile payment adoption among retailers in Ghana. The study contributes to the literature on mobile payment adoption from developing country context.

Keywords: mobile payment, retailers, structural equation modeling, technology acceptance model

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Authors: Sina Alimohammadi, Mahnaz Banihashemi, Maryam Poursharif

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Demodex is a mandatory parasite of pilosebaceous. D. folliculorum lives as a single parasite or as a number of parasites in hair follicles, and D. brevis as a single parasite living in sebaceous glands. Transmission of Demodex from one person to another requires direct skin contact; it also has a greater density in the forehead, cheeks, nose, and nasolabial folds. Demodex can cause some clinical symptoms such as follicular pityriasis, rosacea-like demodicosis, postural folliculitis, papules, seborrheic dermatitis, blepharitis, dermatitis around the lips, and hyperpigmented spots. In this study, the prevalence of Demodex species in patients referred to the dermatology department of Sayad Shirazi Hospital Gorgan, Iran, in the years 2019-2020 was investigated. Material and Methods: The study population consisted of 242 samples taken from the people referred to the dermatology department of Sayad Shirazi Hospital during the years 2019-2020, which were sampled by adhesive tape. All of the participants completed the questionnaires. The samples were examined microscopically for the presence of Demodex. Results: Out of 242 participants, 67 (27.68%) were infected with Demodex. Most cases of infection were observed in the group of 21 to 30 years (28 people; 11.57%) and then in the group of 31 to 40 years (21 people; 8.67%). Also, in the group of people under 10 years and over 60 years, no positive cases (0%) of Demodex were observed in microscopic examinations. Out of 11 variables, there was a statistically significant difference in relation to the three variables of age (P = 0.000003), use of cleansing solutions (P = 0.002), and the presence of acne (P = 0.0013). Conclusion: According to the results of this study, it was found that the incidence of Demodex in one group of acne patients is higher than in others, which emphasizes the possible role of Demodex in the pathogenesis of acne. In this study, there was an inverse relationship between the incidence of Demodex and the use of skin cleansing solutions. Also, the prevalence of Demodex is higher in the group of 20-30 years, and its prevalence does not increase with age. Due to the possibility of drug resistance in the future, regular studies on genotyping and drug resistance are recommended.

Keywords: acne, demodex, mite, prevalence

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Authors: Sahar B. Ahmed, M. Mostafa Said, Mona I. Mohamed

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Streptozotocin (STZ) caused a significant increase in blood glucose and malondialdehyde (MDA) levels in serum accompanied by a significant decrease in blood reduced glutathione (GSH) and superoxide dismutase (SOD) activities. Also, ALT, AST, albumin and urea were markedly affected by STZ injection. The oral administration of Mango leaves extract (MLE) one hour before STZ injection was significantly improved the blood glucose level, ALT, AST activities, albumin and urea that associated with the regulation of MDA, GSH and SOD levels. The antimicrobial activity of MLE showed a significant inhibitory activity against multidrug resistant gram positive and gram negative bacteria isolated from patients in Egyptian hospitals especially Salmonella typhi and typhimurium. In conclusion, results revealed the antioxidant, hypoglycemic effect and antimicrobial potentials of MLE under investigation. Further studies will be needed to investigate the prolonged period of MLE administration and its possible side effects.

Keywords: aqueous extract of mango leaves, STZ, antioxidant, hypoglycemic effect, antimicrobial potentials.

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

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Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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Authors: Jenny Hall, Alison Jaquet

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Universities’ push toward the production of high quality research is not limited to academic staff and experienced researchers. In this environment of research rich agendas, Higher Degree Research (HDR) students are increasingly expected to engage in the publishing of good quality papers in high impact journals. IFN001: Advanced Information Research Skills (AIRS) is a credit bearing mandatory coursework requirement for Queensland University of Technology (QUT) doctorates. Since its inception in 1989, this unique blended learning program has provided the foundations for new researchers to produce original and innovative research. AIRS was redeveloped in 2012, and has now been evaluated with reference to the university’s strategic research priorities. Our research is the first comprehensive evaluation of the program from the learner perspective. We measured whether the program develops essential transferrable skills and graduate capabilities to ensure best practice in the areas of publishing and data management. In particular, we explored whether AIRS prepares students to be agile researchers with the skills to adapt to different research contexts both within and outside academia. The target group for our study consisted of HDR students and supervisors at QUT. Both quantitative and qualitative research methods were used for data collection. Gathering data was by survey and focus groups with qualitative responses analyzed using NVivo. The results of the survey show that 82% of students surveyed believe that AIRS assisted their research process and helped them learn skills they need as a researcher. The 18% of respondents who expressed reservation about the benefits of AIRS were also examined to determine the key areas of concern. These included trends related to the timing of the program early in the candidature and a belief among some students that their previous research experience was sufficient for postgraduate study. New insights have been gained into how to better support HDR learners in partnership with supervisors and how to enhance learning experiences of specific cohorts, including international students and mature learners.

Keywords: data management, enhancing learning experience, publishing, research higher degree students, doctoral students

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Authors: Muneeb Ahmad, Ali Raza

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A computational method inspired by the immune system (IS) is presented, leveraging its shared characteristics of robustness, fault tolerance, scalability, and adaptability with swarm intelligence. This method aims to showcase flocking behaviors in a swarm of robots (SR). The innate part of the IS offers a variety of reactive and probabilistic cell functions alongside its self-regulation mechanism which have been translated to enable swarming behaviors. Although, the research is specially focused on flocking behaviors in a variety of simulated environments using e-puck robots in a physics-based simulator (CoppeliaSim); the artificial innate immune system (AIIS) can exhibit other swarm behaviors as well. The effectiveness of the immuno-inspired approach has been established with extensive experimentations, for scalability and adaptability, using standard swarm benchmarks as well as the immunological regulatory functions (i.e., Dendritic Cells’ Maturity and Inflammation). The AIIS-based approach has proved to be a scalable and adaptive solution for emulating the flocking behavior of SR.

Keywords: artificial innate immune system, flocking swarm, immune system, swarm intelligence

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