Search results for: therapeutic exercise

Authors: Abenezer Nigussie

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Strategic control practice is a critical exercise, as it provides a sturdy influence towards firms or production partners to achieve the full implementation of effective predetermined plans. The importance of strategic control in a company is often measured by observing the relationship between strategic management and organizational performance. The conventional philosophy of strategic control in academia and the industry places significant emphasis on the ability to plan and execute initiatives. In contrast, the same emphasis on strategic management has received less attention in the housing industry. Although the pressures of project performance can often obscure the wider social, economic, and professional context in which strategic management is undertaken, it is these broad contextual areas that make strategic control a vital issue for construction businesses. Rapidly changing social and technological issues are creating an informed environment that will appear very different in the coming decades from what is experienced in today’s companies. Construction project activity is not adequately led by strategic management tools; projects are mostly executed through simple plans and schedules. The issues that this thesis addresses and solves involve the successful accompaniment of the construction project process through these strategic management tools. The second important aspect is an evaluation of project activity, which is mostly done through simple economic and technical valuation. However, during this research, effective strategic management tools are evaluated and suggested for the assessment of project activities. The research introduces a study of the current strategic management practices of construction companies and also presents the concept of strategic management and the areas that companies need to address to compete in the global market. A summary of an industry survey is documented along with the historical research that prompted the investigation of these topics with a focus on the implementation of tools. Strategic management is a concept that concerns making decisions and taking corrective actions to achieve the future goals and objectives of a company. The objective of this paper is to review the practice of strategic management in construction companies. Questionnaires were distributed to major construction companies listed under categories of each project capable of specifying the complete expression of strategic management tools. Findings of the research showed that the majority of development companies practice strategic management tools in the process and implementation of each tool.

Keywords: strategic management, management, analysis, project management

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Authors: Michela Terlizzi, Chiara Colarusso, Aldo Pinto, Rosalinda Sorrentino

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Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer, although its exact role is still elusive. Based on our previous study in which we found that S1P/S1PR3 is involved in an inflammatory pattern via the activation of Toll-like Receptor 9 (TLR9), highly expressed on lung cancer cells, the main goal of the current study was to better understand the involvement of S1P/S1PR3 pathway/signaling during lung carcinogenesis, taking advantage of a mouse model of first-hand smoke exposure and of carcinogen-induced lung cancer. We used human samples of Non-Small Cell Lung Cancer (NSCLC), a mouse model of first-hand smoking, and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. We found that the intranuclear, but not the membrane, localization of S1PR3 was associated to the proliferation of lung adenocarcinoma cells, the mechanism that was correlated to human and mouse samples of smoke-exposure and carcinogen-induced lung cancer, which were characterized by higher utilization of S1P. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after TLR9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the enzyme responsible for the catalysis of the S1P last step synthesis, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. These results prove that the endogenous TLR9-induced S1P can on one side favor pro-inflammatory mechanisms in the tumor microenvironment via the activation of cell surface receptors, but on the other tumor progression via the nuclear S1PR3/SPHK II axis, highlighting a novel molecular mechanism that identifies S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes and that could provide differential therapeutic approaches especially in non-responsive lung cancer patients.

Keywords: sphingosine-1-phosphate (S1P), S1P Receptor 3 (S1PR3), smoking-mice, lung inflammation, lung cancer

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Authors: Paulina Zavistanaviciute, Vita Krungleviciute, Elena Bartkiene

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Lactic acid bacteria (LAB) are microbial supplements that increase the nutritional, therapeutic, and safety value of food and feed. Often LAB strains are incubated in an expensive commercially available de Man-Rogosa-Sharpe (MRS) medium; the cultures are centrifuged, and the cells are washing with sterile water. Potato juice and apple juice industry bio-products are industrial wastes which may constitute a source of digestible nutrients for microorganisms. Due to their low cost and good chemical composition, potato juice and apple juice production bio- products could have a potential application in LAB encapsulation. In this study, pure LAB (P. acidilactici and P. pentosaceus) were multiplied in a crushed potato juice and apple juice industry bio-products medium. Before using, bio-products were sterilized and filtered. No additives were added to mass, except apple juice industry bioproducts were diluted with sterile water (1/5; v/v). The tap of sterilised mass, and LAB cell suspension (5 mL), containing of 8.9 log10 colony-forming units (cfu) per mL of the P. acidilactici and P. pentosaceus was used to multiply the LAB for 72 h. The final colony number in the potato juice and apple juice bio- products substrate was on average 9.60 log10 cfu/g. In order to stabilize the LAB, several methods of dehydration have been tested: lyophilisation (MilrockKieffer Lane, Kingston, USA) and dehydration in spray drying system (SD-06, Keison, Great Britain). Into the spray drying system multiplied LAB in a crushed potato juice and apple juice bio-products medium was injected in peristaltic way (inlet temperature +60 °C, inlet air temperature +150° C, outgoing air temperature +80 °C, air flow 200 m3/h). After lyophilisation (-48 °C) and spray drying (+150 °C) the viable cell concentration in the fermented potato juice powder was 9.18 ± 0.09 log10 cfu/g and 9.04 ± 0.07 log10 cfu/g, respectively, and in apple mass powder 8.03 ± 0.04 log10 cfu/g and 7.03 ± 0.03 log10 cfu/g, respectively. Results indicated that during the storage (after 12 months) at room temperature (22 +/- 2 ºC) LAB count in dehydrated products was 5.18 log10 cfu/g and 7.00 log10 cfu/g (in spray dried and lyophilized potato juice powder, respectively), and 3.05 log10 cfu/g and 4.10 log10 cfu/g (in spray dried and lyophilized apple juice industry bio-products powder, respectively). According to obtained results, potato juice could be used as alternative substrate for P. acidilactici and P. pentosaceus cultivation, and by drying received powders can be used in food/feed industry as the LAB starters. Therefore, apple juice industry by- products before spray drying and lyophilisation should be modified (i. e. by using different starches) in order to improve its encapsulation.

Keywords: bio-products, encapsulation, lactic acid bacteria, sustainability

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Authors: Li Chun Zhao, Zhi Chao Hu, Xi Qiang Liu, Man Lai Lee, Chak Shing Yeung, Man Fei Xu, Yuen Yee Kwan, Alan H. M. Ho, Nickie W. K. Chan, Bin Deng, Zhong Zhen Zhao, Min Xu

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Background: Chuangxiong Rhizoma (Chuangxion, CX) is one of the most frequently used herbs in Chinese medicine because of its wide therapeutic effects such as vasorelaxation and anti-inflammation. Aim: The purposes of this study are (1) to perform non-targeted / targeted analyses of CX methanol extract and water extract, and compare the present data with previously LC-MS or GC-MS fingerprints; (2) to examine the difference between CX methanol extract and water extract for preliminarily evaluating whether current compound markers of methanol extract from crude CX materials could be suitable for quality control of CX water extract. Method: CX methanol extract was prepared according to the Hong Kong Chinese Materia Medica Standards. DG water extract was prepared by boiling with pure water for three times (one hour each). UHPLC-Q-TOF-MS/MS fingerprint analysis was performed by C18 column (1.7 µm, 2.1 × 100 mm) with Agilent 1290 Infinity system. Experimental data were analyzed by Agilent MassHunter Software. A database was established based on 13 published LC-MS and GC-MS CX fingerprint analyses. Total 18 targeted compounds in database were selected as markers to compare present data with previous data, and these markers also used to compare CX methanol extract and water extract. Result: (1) Non-targeted analysis indicated that there were 133 compounds identified in CX methanol extract, while 325 compounds in CX water extract that was more than double of CX methanol extract. (2) Targeted analysis further indicated that 9 in 18 targeted compounds were identified in CX methanol extract, while 12 in 18 targeted compounds in CX water extract that showed a lower lose-rate of water extract when compared with methanol extract. (3) By comparing CX methanol extract and water extract, Senkyunolide A (+1578%), Ferulic acid (+529%) and Senkyunolide H (+169%) were significantly higher in water extract when compared with methanol extract. (4) Other bioactive compounds such as Tetramethylpyrazine were only found in CX water extract. Conclusion: Many new compounds in both CX methanol and water extracts were found by using UHPLC Q-TOF MS/MS analysis when compared with previous published reports. A new standard reference including non-targeted compound profiling and targeted markers functioned especially for quality control of CX water extract (herbal decoction) should be established in future. (This project was supported by Hong Kong Baptist University (FRG2/14-15/109) & Natural Science Foundation of Guangdong Province (2014A030313414)).

Keywords: Chuanxiong rhizoma, fingerprint analysis, targeted analysis, quality control

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Authors: Mohaammad Ahmadpanah, Amineh Akhondi, Mohammad Haghighi, Ali Ghaleiha, Leila Jahangard, Elham Salari

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Background: Working memory includes the capability to keep and manipulate information in a short period of time. This capability is the basis of complicated judgments and has been attended to as the specific and constant character of individuals. Children with attention deficit and hyperactivity are among the people suffering from deficiency in the active memory, and this deficiency has been attributed to the problem of frontal lobe. This study utilizes a new approach with suitable tasks and methods for training active memory and assessment of the effects of the trainings. Participants: The children participating in this study were of 7-15 year age, who were diagnosed by the psychiatrist and psychologist as hyperactive and attention deficit based on DSM-IV criteria. The intervention group was consisted of 8 boys and 6 girls with the average age of 11 years and standard deviation of 2, and the control group was consisted of 2 girls and 5 boys with an average age of 11.4 and standard deviation of 3. Three children in the test group and two in the control group were under medicinal therapy. Results: Working memory training meaningfully improved the performance in not-trained areas as visual-spatial working memory as well as the performance in Raven progressive tests which are a perfect example of non-verbal, complicated reasoning tasks. In addition, motional activities – measured based on the number of head movements during computerized measuring program – was meaningfully reduced in the medication group. The results of the second test showed that training similar exercise to teenagers and adults results in the improvement of cognition functions, as in hyperactive people. Discussion: The results of this study showed that the performance of working memory is improved through training, and these trainings are extended and generalized in other areas of cognition functions not receiving any training. Trainings resulted in the improvement of performance in the tasks related to prefrontal. They had also a positive and meaningful impact on the moving activities of hyperactive children.

Keywords: attention deficit hyperactivity disorder, working memory, non-medical treatment, children

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Authors: Shaimaa Eltanani, Thangal Yumnamcha, Ahmed S. Ibrahim

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Purpose: Mitochondria dysfunction is central to breaking the barrier integrity of retinal endothelial cells (RECs) in various blinding eye diseases such as diabetic retinopathy and retinopathy of prematurity. Therefore, we aimed to dissect the role of different mitochondrial components, specifically, those of oxidative phosphorylation (OxPhos), in maintaining the barrier function of RECs. Methods: Electric cell-substrate impedance sensing (ECIS) technology was used to assess in real-time the role of different mitochondrial components in the total impedance (Z) of human RECs (HRECs) and its components; the capacitance (C) and the total resistance (R). HRECs were treated with specific mitochondrial inhibitors that target different steps in OxPhos: Rotenone for complex I; Oligomycin for ATP synthase; and FCCP for uncoupling OxPhos. Furthermore, data were modeled to investigate the effects of these inhibitors on the three parameters that govern the total resistance of cells: cell-cell interactions (Rb), cell-matrix interactions (α), and cell membrane permeability (Cm). Results: Rotenone (1 µM) produced the greatest reduction in the Z, followed by FCCP (1 µM), whereas no reduction in the Z was observed after the treatment with Oligomycin (1 µM). Following this further, we deconvoluted the effect of these inhibitors on Rb, α, and Cm. Firstly, rotenone (1 µM) completely abolished the resistance contribution of Rb, as the Rb became zero immediately after the treatment. Secondly, FCCP (1 µM) eliminated the resistance contribution of Rb only after 2.5 hours and increased Cm without considerable effect on α. Lastly, Oligomycin had the lowest impact among these inhibitors on Rb, which became similar to the control group at the end of the experiment without noticeable effects on Cm or α. Conclusion: These results demonstrate differential roles for complex I, complex V, and coupling of OxPhos in maintaining the barrier functionality of HRECs, in which complex I being the most important component in regulating the barrier functionality and the spreading behavior of HRECs. Such differences can be used in investigating gene expression as well as for screening selective agents that improve the functionality of complex I to be used in the therapeutic approach for treating REC-related retinal diseases.

Keywords: human retinal endothelial cells (hrecs), rotenone, oligomycin, fccp, oxidative phosphorylation, oxphos, capacitance, impedance, ecis modeling, rb resistance, α resistance, and barrier integrity

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Authors: Deeba N. Baig, Ateeqa Ijaz, Saloome Rafiq

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Camel is a religious and culturally significant animal in Asian and African regions. In Pakistan Dromedary and Bactrian are common camel breeds. Other than the transportation use, it is a pivotal source of milk and meat. The quality of its milk and meat is predominantly dependent on the geographical location and variety of vegetation available for the diet. Camel milk (CM) is highly nutritious because of its reduced cholesterol and sugar contents along with enhanced minerals and vitamins level. The absence of beta-lactoglobulin (like human milk), makes CM a safer alternative for infants and children having Cow Milk Allergy (CMA). In addition to this, it has a unique probiotic profile both in raw and fermented form. Number of Lactic acid bacteria (LAB) including lactococcus, lactobacillus, enterococcus, streptococcus, weissella, pediococcus and many other bacteria have been detected. From these LAB Lactobacilli, Bifidobacterium and Enterococcus are widely used commercially for fermentation purpose. CM has high therapeutic value as its effectiveness is known against various ailments like fever, arthritis, asthma, gastritis, hepatitis, Jaundice, constipation, postpartum care of women, anti-venom, dropsy etc. It also has anti-diabetic, anti-microbial, antitumor potential along with its robust efficacy in the treatment of auto-immune disorders. Recently, the role of CM has been explored in brain-gut axis for the therapeutics of neurodevelopmental disorders. In this connection, a lot of grey area was available to explore the probiotics and therapeutics latent in the CM available in Pakistan. Thus, current study was designed to explore the predominant probiotic flora and antimicrobial potential of CM from different local breeds of Pakistan. The probiotics have been identified through biochemical, physiological and ribo-typing methods. In addition to this, bacteriocins (antimicrobial-agents) were screened through PCR-based approach. Results of this study revealed that CM from different breeds of camel depicted a number of similar probiotic candidates along with the range of limited variability. However, the nucleotide sequence analysis of selected anti-listerial bacteriocins exposed least variability. As a conclusion, the CM has sufficient probiotic availability and significant anti-microbial potential.

Keywords: bacteriocins, camel milk, probiotics potential, therapeutics

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Authors: Azariah Sosa, Carlos Renedo Sanchez

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The development of a new motorway north of Auckland (New Zealand) includes steep rock cuts, from 63 up to 85 degrees, in an interbedded sandstone and siltstone rock mass of the geological unit Waitemata Group (Pakiri Formation), which shows sub-horizontal bedding planes, various sub-vertical joint sets, and a diverse weathering profile. In this kind of rock mass -that can be classified as a weak rock- the definition of the stable maximum geometry is not only governed by discontinuities and defects evident in the rock but is important to also consider the global stability of the rock slope, including (in the analysis) the rock mass characterisation, influence of the groundwater, the geological evolution, and the weathering processes. Depending on the weakness of the rock and the processes suffered, the global stability could, in fact, be a more restricting element than the potential instability of individual blocks through discontinuities. This paper discusses those elements that govern the stability of the rock slopes constructed in a rock formation with favourable bedding and distribution of discontinuities (horizontal and vertical) but with a weak behaviour in terms of global rock mass characterisation. In this context, classifications as Q-Slope and slope stability assessment methodology (SSAM) have been demonstrated as important tools which complement the assessment of the global stability together with the analytical tools related to the wedge-type failures and limit equilibrium methods. The paper focuses on the applicability of these two new empirical classifications to evaluate the slope stability in 18 already excavated rock slopes in the Pakiri formation through comparison between the predicted and observed stability issues and by reviewing the outcome of analytical methods (Rocscience slope stability software suite) compared against the expected stability determined from these rock classifications. This exercise will help validate such findings and correlations arising from the two empirical methods in order to adjust the methods to the nature of this specific kind of rock mass and provide a better understanding of the long-term stability of the slopes studied.

Keywords: Pakiri formation, Q-slope, rock slope stability, SSAM, weak rock

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Authors: Anjana Aggarwal, Sheilja Walia

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Prevalence of obesity and overweight is increasing due to sedentary lifestyles and busy schedules of people that spend less time on physical exercise. To reduce weight, people are finding easier and more convenient ways. The easiest solution is the use of dietary supplements and fat burners. These are products that decrease body weight by increasing the basal metabolic rate. Various reports have been published on the consumption of fat burners leading to heart palpitations, seizures, anxiety, depression, psychosis, bradycardia, insomnia, muscle contractions, hepatotoxicity, and even liver failure. Case reports and series are reporting that the ingredients present in the fat burners caused acute liver failure (ALF) and hepatic toxicity in many cases. Another contributing factor is the absence of regulations from the Food and Drug Administration on these products, leading to increased consumption and a higher risk of liver diseases among the population. This systematic review aims to attain a better understanding of the dietary supplements used globally to reduce weight and document the case reports/series of acute liver failure caused by the consumption of fat burners. Electronic databases like PubMed, Cochrane, Google Scholar, etc., will be systematically searched for relevant articles. Various websites of dietary products and brands that sell such supplements, Journals of Hepatology, National and international projects launched for ALF, and their reports, along with the review of grey literature, will also be done to get a better understanding of the topic. After discussing with the co-author, the selection and screening of the articles will be performed by the author. The studies will be selected based on the predefined inclusion and exclusion criteria. The case reports and case series that will be included in the final list of the studies will be assessed for methodological quality using the CARE guidelines. The results from this study will provide insights and a better understanding of fat burners. Since the supplements are easily available in the market without any restrictions on their sale, people are unaware of their adverse effects. The consumption of these supplements causes acute liver failure. Thus, this review will provide a platform for future larger studies to be conducted.

Keywords: acute liver failure, dietary supplements, fat burners, weight loss supplements

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Authors: Caroline Bradbury-Jones, Maria Clark, Eleanor Molloy, Nicki Ward

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Background: Significant developments in the protection of Lesbian, Gay, Bisexual, Transgender and Queer (LGBTQ) rights culminated in their inclusion in the Equality Act 2010. This provides legal protection against discrimination including the Public Sector Equality Duty requiring public bodies to consider all individuals when carrying out their day-to-day work. In the UK, whilst the Higher Education sector has made some commitment to eliminating discrimination and addressing LGBTQ inclusivity, there are two particular problems specifically affecting students on professional programmes: -All students will come into contact with LGBTQ patients/clients/students and need to be equipped to respond appropriately to their diverse needs but evidence suggests that this is not always the case. -Many LGBTQ students have specific concerns on professional placements; often ‘going back in the closet’ or feeling uncertain how to respond to questions about their personal lives and being reticent to challenge discrimination against LGBTQ patients/clients/students for fear of reprisal. Study aim: To investigate how best to prepare all students to deal with the issue of gender and sexual diversity and to support LGBTQ students in negotiating (non) disclosure in practice placements. Methods: This multi-method study was conducted in 2017 in the UK. It comprised a student survey, focus group interview with students and a national benchmarking exercise. Findings: Preliminary findings are that there is considerable variation across professional programmes regarding the preparation of students to respond to LGBTQ issues. Similarly, there is considerable difference between the level of preparedness experienced by students irrespective of whether they identify as LGBTQ. Discussion: Nationally there are a number of ‘best practice’ examples that we share in this presentation. These contain important details and guidance about how to better prepare university students for professional practice, and to contribute to eliminating discrimination and addressing LGBTQ inclusivity. Conclusions: The presentation will appeal to delegates who are interested in the equality agenda regarding LGBTQ people. The study findings will be discussed and debated to explore their impact on higher education and learning and to identify ways to integrate best practice into professional curricula across the UK and beyond.

Keywords: diversity, equality, practice, sexuality, students, university

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Authors: Najia Zulfiqar

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Imparting moral education is the need of time, considering the obvious moral decline in society. Recent research shows the downfall of moral competence among university students. The main objective of the present study was to develop moral development intervention strategies for undergraduate students of Sports and Physical Education. Using an interpretative phenomenological approach, insight into field-specific moral issues was gained through interviews with 7 subject experts and a focus-group discussion session with 8 students. Two research assistants who were trained in qualitative interviewing collected, transcribed and analyzed data into the MAXQDA software using content and discourse analyses. The identified moral issues in Sports and Physical Education were sports gambling and betting, pay-for-play, doping, coach misconduct, tampering, cultural bias, gender equity/nepotism, bullying/discrimination, and harassment. Next, intervention modules were developed for each moral issue based on hypothetical situations, and followed by guided reflection and dilemma discussion questions. The third moral development strategy was community services that included posture screening, diet plan for different age groups, open fitness ground training, exercise camps for physical fitness, balanced diet awareness camp, gymnastic camp, shoe assessment as per health standards, and volunteering for public awareness at the playground, gymnasium, stadium, park, etc. The intervention modules were given to four subject specialists for expert validation who were from different backgrounds within Sport Sciences. Upon refinement and finalization, four students were presented with these intervention modules and questioned about accuracy, relevance, comprehension, and content organization. Iterative changes were made in the content of the intervention modules to tailor them to the moral development needs of undergraduate students. This intervention will strengthen positive moral values and foster mature decision-making about right and wrong acts. As this intervention is easy to apply as a remedial tool, academicians and policymakers can use this to promote students’ moral development.

Keywords: community service, dilemma discussion, morality, physical education, university students.

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Authors: Shashwat, Sandra G. L. Persiani, Yew Wah Wong, Pramod S. Kamath, Avinash H. Anantharam, Hui Ling Aw, Yann Grynberg

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Achieving zero-energy targets in existing buildings is known to be a difficult task, hence targets are addressed at new buildings almost exclusively. Although these ultra-efficient case-studies remain essential to develop future technologies and drive the concepts of Zero-energy, the immediate need to cut the consumption of the existing building stock remains unaddressed. This work aims to present a reliable and straightforward methodology for assessing the potential of energy-efficient upgrading in existing buildings. Public Singaporean school buildings, characterized by low energy use intensity and large roof areas, were identified as potential objects for conversion to highly-efficient buildings with a positive energy balance. A first study phase included the development of a detailed energy model for two case studies (a primary and a secondary school), based on the architectural drawings provided, site-visits and calibrated using measured end-use power consumption of different spaces. The energy model was used to demonstrate compliances or predict energy consumption of proposed changes in the two buildings. As complete energy monitoring is difficult and substantially time-consuming, short-term energy data was collected in the schools by taking spot measurements of power, voltage, and current for all the blocks of school. The figures revealed that the bulk of the consumption is attributed in decreasing order of magnitude to air-conditioning, plug loads, and lighting. In a second study-phase, a number of energy-efficient technologies and strategies were evaluated through energy-modeling to identify the alternatives giving the highest energy saving potential, achieving a reduction in energy use intensity down to 19.71 kWh/m²/y and 28.46 kWh/m²/y for the primary and the secondary schools respectively. This exercise of field evaluation and computer simulation of energy saving potential aims at a preliminary assessment of the positive-energy feasibility enabling future implementation of the technologies on the buildings studied, in anticipation of a broader and more widespread adoption in Singaporean schools.

Keywords: energy simulation, school building, tropical climate, zero energy buildings, positive energy

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Authors: Deepthy Ann Joy, N. Sreedevi

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Hearing impairment (HI) at an early age, identified before the onset of language development can reduce the negative effect on speech and language development of children. Early rehabilitation is very important in the improvement of speech production in children with HI. Other than conventional hearing aids, Cochlear Implants are being used in the rehabilitation of children with HI. However, delay in acquisition of speech and language milestones persist in children with Cochlear Implant (CI). Delay in speech milestones are reflected through speech sound errors. These errors reflect the temporal and spectral characteristics of speech. Hence, acoustical analysis of the speech sounds will provide a better representation of speech production skills in children with CI. The present study aimed at investigating the acoustic characteristics of vowels in Malayalam speaking children with a cochlear implant. The participants of the study consisted of 20 Malayalam speaking children in the age range of four and seven years. The experimental group consisted of 10 children with CI, and the control group consisted of 10 typically developing children. Acoustic analysis was carried out for 5 short (/a/, /i/, /u/, /e/, /o/) and 5 long vowels (/a:/, /i:/, /u:/, /e:/, /o:/) in word-initial position. The responses were recorded and analyzed for acoustic parameters such as Vowel duration, Ratio of the duration of a short and long vowel, Formant frequencies (F₁ and F₂) and Formant Centralization Ratio (FCR) computed using the formula (F₂u+F₂a+F₁i+F₁u)/(F₂i+F₁a). Findings of the present study indicated that the values for vowel duration were higher in experimental group compared to the control group for all the vowels except for /u/. Ratio of duration of short and long vowel was also found to be higher in experimental group compared to control group except for /i/. Further F₁ for all vowels was found to be higher in experimental group with variability noticed in F₂ values. FCR was found be higher in experimental group, indicating vowel centralization. Further, the results of independent t-test revealed no significant difference across the parameters in both the groups. It was found that the spectral and temporal measures in children with CI moved towards normal range. The result emphasizes the significance of early rehabilitation in children with hearing impairment. The role of rehabilitation related aspects are also discussed in detail which can be clinically incorporated for the betterment of speech therapeutic services in children with CI.

Keywords: acoustics, cochlear implant, Malayalam, vowels

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Authors: Ayesha Waqar Khan, Mariam Altaf, Jamil Ahmad, Shaheen Shahzad

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Kidney fibrosis is an anticipated outcome of possibly all types of progressive chronic kidney disease (CKD). Epithelial-mesenchymal transition (EMT) signaling pathway is responsible for production of matrix-producing fibroblasts and myofibroblasts in diseased kidney. In this study, a discrete model of TGF-beta (transforming growth factor) and CTGF (connective tissue growth factor) was constructed using Rene Thomas formalism to investigate renal fibrosis turn over. The kinetic logic proposed by Rene Thomas is a renowned approach for modeling of Biological Regulatory Networks (BRNs). This modeling approach uses a set of constraints which represents the dynamics of the BRN thus analyzing the pathway and predicting critical trajectories that lead to a normal or diseased state. The molecular connection between TGF-beta, Smad 2/3 (transcription factor) phosphorylation and CTGF is modeled using GenoTech. The order of BRN is CTGF, TGF-B, and SMAD3 respectively. The predicted cycle depicts activation of TGF-B (TGF-β) via cleavage of its own pro-domain (0,1,0) and presentation to TGFR-II receptor phosphorylating SMAD3 (Smad2/3) in the state (0,1,1). Later TGF-B is turned off (0,0,1) thereby activating SMAD3 that further stimulates the expression of CTGF in the state (1,0,1) and itself turns off in (1,0,0). Elevated CTGF expression reactivates TGF-B (1,1,0) and the cycle continues. The predicted model has generated one cycle and two steady states. Cyclic behavior in this study represents the diseased state in which all three proteins contribute to renal fibrosis. The proposed model is in accordance with the experimental findings of the existing diseased state. Extended cycle results in enhanced CTGF expression through Smad2/3 and Smad4 translocation in the nucleus. The results suggest that the system converges towards organ fibrogenesis if CTGF remains constructively active along with Smad2/3 and Smad 4 that plays an important role in kidney fibrosis. Therefore, modeling regulatory pathways of kidney fibrosis will escort to the progress of therapeutic tools and real-world useful applications such as predictive and preventive medicine.

Keywords: CTGF, renal fibrosis signaling pathway, system biology, qualitative modeling

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Authors: Sophio Kobauri, David Tugushi, Vladimir P. Torchilin, Ramaz Katsarava

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Hydrophobic / hydrophilically modified functional polymers are of high interest in modern biomedicine due to their ability to solubilize water-insoluble / poorly soluble (hydrophobic) drugs. Among the many approaches that are being developed in this direction, one of the most effective methods is the use of polymeric micelles (PMs) (micelles formed by amphiphilic block-copolymers) for solubilization of hydrophobic biologicals. For therapeutic purposes, PMs are required to be stable and biodegradable, although quite a few amphiphilic block-copolymers are described capable of forming stable micelles with good solubilization properties. For obtaining micelle-forming block-copolymers, polyethylene glycol (PEG) derivatives are desirable to use as hydrophilic shell because it represents the most popular biocompatible hydrophilic block and various hydrophobic blocks (polymers) can be attached to it. Although the construction of the hydrophobic core, due to the complex requirements and micelles structure development, is the very actual and the main problem for nanobioengineers. Considering the above, our research goal was obtaining biodegradable micelles for the solubilization of hydrophobic drugs and biologicals. For this purpose, we used biodegradable polymers– pseudo-proteins (PPs)(synthesized with naturally occurring amino acids and other non-toxic building blocks, such as fatty diols and dicarboxylic acids) as hydrophobic core since these polymers showed reasonable biodegradation rates and excellent biocompatibility. In the present study, we used the hydrophobic amino acid – L-phenylalanine (MW 4000-8000Da) instead of L-leucine. Amino-PEG (MW 2000Da) was used as hydrophilic fragments for constructing the suitable micelles. The molecular weight of PP (the hydrophobic core of micelle) was regulated by variation of used monomers ratios. Micelles were obtained by dissolving of synthesized amphiphilic polymer in water. The micelle-forming property was tested using dynamic light scattering (Malvern zetasizer NanoZSZEN3600). The study showed that obtaining amphiphilic block-copolymer form stable neutral micelles 100 ± 7 nm in size at 10mg/mL concentration, which is considered as an optimal range for pharmaceutical micelles. The obtained preliminary data allow us to conclude that the obtained micelles are suitable for the delivery of poorly water-soluble drugs and biologicals.

Keywords: amino acid – L-phenylalanine, pseudo-proteins, amphiphilic block-copolymers, biodegradable micelles

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Authors: Nigatu Tadesse, Ying Liu, Juan Li, Hong Ming Liu

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Gastric carcinogenesis is a lengthy process of histopathological transition from normal to atrophic gastritis (AG) to intestinal metaplasia (GIM), dysplasia toward gastric cancer (GC). The stage of GIM identified as precancerous lesions with resistance to H-pylori eradication and recurrence after endoscopic surgical resection therapies. GIM divided in to two morphologically distinct phenotypes such as complete GIM bearing intestinal type morphology whereas the incomplete type has colonic type morphology. The incomplete type GIM considered to be the greatest risk factor for the development of GC. Studies indicated the expression of the caudal type homeobox 2 (CDX2) gene is responsible for the development of complete GIM but its progressive downregulation from incomplete metaplasia toward advanced GC identified as the risk for IM progression and neoplastic transformation. The downregulation of CDX2 gene have promoted cell growth and proliferation in gastric and colon cancers and ascribed in chemo-treatment inefficacies. CDX2 downregulated through promoter region hypermethylation in which the methylation frequency positively correlated with the dietary history of the patients, suggesting the role of diet as methyl carbon donor sources such as methionine. However, the metabolism of exogenous methionine is yet unclear. Targeting exogenous methionine metabolism has become a promising approach to limits tumor cell growth, proliferation and progression and increase treatment outcome. This review article discusses molecular alterations that could shed light on the potential of exogenous methionine metabolisms, such as gut microbiota alteration as sources of methionine to host cells, metabolic pathway signaling via PI3K/AKt/mTORC1-c-MYC to rewire exogenous methionine and signature of increased gene methylation index, cell growth and proliferation in GIM, with insights to new treatment avenue via targeting methionine metabolism, and the need for future integrated studies on molecular alterations and metabolomics to uncover altered methionine metabolism and characterization of CDX2 methylation in gastric intestinal metaplasia for potential therapeutic exploitation.

Keywords: altered methionine metabolism, Intestinal metaplesia, CDX2 gene, gastric cancer

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Authors: Scott R. Butler

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Ontario, Canada’s largest province, is in the midst of an interesting experiment in mandated asset management planning for local governments. At the beginning of 2021, Ontario’s 444 municipalities were responsible for the management of 302,864 lane kilometers of roads that have a replacement cost of $97.545 billion CDN. Roadways are by far the most complex, expensive, and extensive assets that a municipality is responsible for overseeing. Since adopting Ontario Regulation 588/47: Asset Management Planning for Municipal Infrastructure in 2017, the provincial government has established prescriptions for local road authorities regarding asset category and levels of service being provided. This provincial regulation further stipulates that asset data such as extent, condition, and life cycle costing are to be captured in manner compliant with qualitative descriptions and technical metrics. The Ontario Good Roads Association undertook an exercise to aggregate the road-related data contained within the 444 asset management plans that municipalities have filed with the provincial government. This analysis concluded that collectively Ontario municipal roadways have a $34.7 billion CDN in deferred maintenance. The ill-state of repair of Ontario municipal roads has lasting implications for province’s economic competitiveness and has garnered considerable political attention. Municipal efforts to address the maintenance backlog are stymied by the extremely limited fiscal parameters municipalities must operate within in Ontario. Further exacerbating the program are provincially designed programs that are ineffective, administratively burdensome, and not necessarily aligned with local priorities or strategies. This paper addresses how municipal asset management plans – and more specifically, the data contained in these plans – can be used to design innovative policy frameworks, flexible funding programs, and new levels of service that respond to these funding challenges, as well as emerging issues such as local economic development and climate change. To fully unlock the potential that Ontario Regulation 588/17 has imposed will require a resolute commitment to data standardization and horizontal collaboration between municipalities within regions.

Keywords: transportation, municipal asset management, subnational policy design, subnational funding program design

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Authors: J. Wozniak-Holecka, T. Holecki, P. Romaniuk

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Spa facilities are being perceived as the ways of healing treatment in Poland and are guaranteed within the public financing. The universal health insurance (National Health Fund, NFZ), and the disability prevention programme held by Social Insurance Institution (ZUS) are the main sources of financing spa facilities. The dominant public payer of spa services is the NFZ. The Social Insurance Institution covers the cost of health treatment realized in spa facilities as medical rehabilitation, in the field of disability prevention. Health services delivered in the spa resorts are characterized by complexity, and the combination of various methods, typical for health prevention, education, balneotherapy, and physiotherapy. Healing with natural methods, believed to enhance the therapeutic effect, is also involved in health spa treatment. Regardless of the type of facility, each form of spa treatment includes health promotion, health education, prevention at all levels, including rehabilitation. The aim of the study was to determine the optimal organization of health education process. Its efficiency strongly depends on the type of service provider and the funding institution (NFZ vs ZUS). It results from the use of different measures of the effectiveness, the quality and the evaluation of the process being assessed by funding institutions. The methods of the study include a comparative and descriptive quantitative and qualitative analysis. In the empirical part, a questionnaire had been developed. It was then distributed among spa personnel, responsible directly for the health promotion, and among patients who are beneficiaries of health services in spa centers. The quantitative part of the study was based on interviews carried with the use of the online survey (CAWI: Computer-Assisted Web Interview), telephone survey (CATI: Computer-Assisted Telephone Interview) and a conventional questionnaire (PAPI: Paper over Pencil Interview). As a result of the conducted research, it was found that the effectiveness of health education activities in spa resort facilities in Poland is higher when the services are organized using structured tools for managerial control. This applies to formalized procedures implemented by one of the dominant payers covering costs of services (ZUS) and involves the application of health education as one of the mandatory elements of treatment, subjected to the process of control during the course of spa therapy and evaluation after it is completed.

Keywords: effectiveness, health education, public health system, spa treatment

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Authors: Shouta Sora, Shizuki Kuriu, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

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Lymph node (LN) metastasis accounts for 20 - 30 % of all deaths in patients with head and neck cancer. Therefore, the control of metastatic lymph nodes (MLNs) is necessary to improve the life prognosis of patients with cancer. In a classical metastatic theory, tumor cells are thought to metastasize hematogenously through a bead-like network of lymph nodes. Recently, a lymph node-mediated hematogenous metastasis theory has been proposed, in which sentinel LNs are regarded as a source of distant metastasis. Therefore, the treatment of MLNs at the early stage is essential to prevent distant metastasis. Radiation therapy is one of the primary therapeutic modalities in cancer treatment. In addition, total body irradiation (TBI) has been reported to act as activation of natural killer cells and increase of infiltration of CD4+ T-cells to tumor tissues. However, the treatment effect of TBI for MLNs remains unclear. This study evaluated the possibilities of low-dose total body irradiation (L-TBI) and middle-dose total body irradiation (M-TBI) for the treatment of MLNs. Mouse breast cancer FM3A-Luc cells were injected into subiliac lymph node (SiLN) of MXH10/Mo/LPR mice to induce the metastasis to the proper axillary lymph node (PALN) and lung. Mice were irradiated for the whole body on 4 days after tumor injection. The L-TBI and M-TBI were defined as irradiations to the whole body at 0.2 Gy and 1.0 Gy, respectively. Tumor growth was evaluated by in vivo bioluminescence imaging system. In the non-irradiated group, tumor activities on SiLN and PALN significantly increased over time, and the metastasis to the lung from LNs was confirmed 28 days after tumor injection. The L-TBI led to a tumor growth delay in PALN but did not control tumor growth in SiLN and metastasis to the lung. In contrast, it was found that the M-TBI significantly delayed the tumor growth of both SiLN and PALN and controlled the distant metastasis to the lung compared with non-irradiated and L-TBI groups. These results suggest that the M-TBI is an effective treatment method for MLNs in the early stage and distant metastasis from lymph nodes via blood vessels connected with LNs.

Keywords: metastatic lymph node, lung metastasis, radiation therapy, total body irradiation, lymphatic system

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Authors: Diogo Prosdocimi, Don Ross, Matthew Townshend

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Road authorities are mandated within limited budgets to both deliver improved access to basic services and facilitate economic growth. This responsibility is further complicated if maintenance backlogs and funding shortfalls exist, as evident in many countries including South Africa. These conditions require authorities to make difficult prioritisation decisions, with the effect that Road Asset Management Systems with a one-dimensional focus on traffic volumes may overlook the maintenance of low-volume roads that provide isolated communities with vital access to basic services. Given these challenges, this paper overlays the full South African road network with geo-referenced information for population, primary and secondary schools, and healthcare facilities to identify the network of connective roads between communities and basic service centres. This connective network is then rationalised according to the Gross Value Added and number of jobs per mesozone, administrative and functional road classifications, speed limit, and road length, location, and name to estimate the Basic Access Road Network. A two-step floating catchment area (2SFCA) method, capturing a weighted assessment of drive-time to service centres and the ratio of people within a catchment area to teachers and healthcare workers, is subsequently applied to generate a Multivariate Road Index. This Index is used to assign higher maintenance priority to roads within the Basic Access Road Network that provide more people with better access to services. The relatively limited incidence of Basic Access Roads indicates that authorities could maintain the entire estimated network without exhausting the available road budget before practical economic considerations get any purchase. Despite this fact, a final case study modelling exercise is performed for the Namakwa District Municipality to demonstrate the extent to which optimal relocation of schools and healthcare facilities could minimise the Basic Access Road Network and thereby release budget for investment in roads that best promote GDP growth.

Keywords: basic access roads, multivariate road index, road prioritisation, two-step floating catchment area method

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Authors: S. D. Kadir

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Background: Antibiotics have always been at the centrum of the revolution of modern microbiology. Micro-organisms and its pathogenicity, resistant organisms, inappropriate or over usage of various types of antibiotic agents are fuelled multidrug-resistant pathogenic organisms. Our present time review report mainly focuses on the therapeutic condition of antibiotic resistance and the possible roots behind the development of antibiotic resistance in Bangladesh in 2019. Methodology: The systemic review has progressed through a series of research analyses on various manuscripts published on Google Scholar, PubMed, Research Gate, and collected relevant information from established popular healthcare and diagnostic center and its subdivisions all over Bangladesh. Our research analysis on the possible assurance of antibiotic resistance been ensured by the selective medical reports and on random assay on the extent of individual antibiotic in 2019. Results: 5 research articles, 50 medical report summary, and around 5 patients have been interviewed while going through the estimation process. We have prioritized research articles where the research analysis been performed by the appropriate use of the Kirby-Bauer method. Kirby-Bauer technique is preferred as it provides greater efficiency, ensures lower performance expenditure, and supplies greater convenience and simplification in the application. In most of the reviews, clinical and laboratory standards institute guidelines were strictly followed. Most of our reports indicate significant resistance shown by the Beta-lactam drugs. Specifically by the derivatives of Penicillin's, Cephalosporin's (rare use of the first generation Cephalosporin and overuse of the second and third generation of Cephalosporin and misuse of the fourth generation of Cephalosporin), which are responsible for almost 67 percent of the bacterial resistance. Moreover, approximately 20 percent of the resistance was due to the fact of drug pumping from the bacterial cell by tetracycline and sulphonamides and their derivatives. Conclusion: 90 percent of the approximate antibiotic resistance is due to the usage of relative and true broad-spectrum antibiotics. The environment has been created by the following circumstances where; the excessive usage of broad-spectrum antibiotics had led to a condition where the disruption of native bacteria and a series of anti-microbial resistance causing a disturbance of the surrounding environments in medium, leading to a state of super-infection.

Keywords: antibiotics, antibiotic resistance, Kirby Bauer method, microbiology

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Authors: Hassan Wajid, Syed T. Ahmed, Syed G. Haider Jr., Razia Latif, Ahsan Ali, Maira Anam

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The phenomenon of Metamorphosis can be associated with any object, organism, or structure gradually and progressively going through the change of systemic or morphological form. This phenomenon can be integrated while teaching drawing to architecture students. In architectural drawings, metamorphosis’s main focus and purpose are not to completely imitate any object. In the process of drawing, the changes in systemic or morphological form happen until the complete process, and the visuals of the complete process change the drawing, opening up possibilities for the imagination of the perceivers. Metamorphosis in architectural drawings begins with an initial form and, through various noticeable stages, ends up final form or manifestation. How much of the initial form is manifested in the final form and progressively among various intermediate stages becomes an indication of the nature of metamorphosis as a phenomenon. It is important at this stage to clarify that the term metamorphosis is presently being coopted from its original domain, usually in life sciences. In this current exercise, the architectural drawings are to act as an operative analog process transforming one image of art and/or architecture in its broadest sense. That composition is claimed to have come from one source (individual work, a cultural artifact, civilizational remain). It dialectically meets, opposes, or confronts some carefully chosen alien opposites from a different domain. As an example, the layers of a detailed drawing of a Turkish prayer rug of 5 x 7 ratio over a detailed architectural plan of a religious, historical complex can be observed such that the two drawings, though at markedly different scales could dialectically converse with one another and through their mutual congruencies. In the final stage, the idea concludes contradictions across the scales to initiate the analogous roles of metamorphosed third reality, which suggests the previous un-acknowledged architectural or artistic identity. The proposed paper explores the trajectory of reproduction by analyzing drawings through detailed drawing stages and analyzes challenges as well as opportunities in the discovered realm of imagination. This description further aims at identifying factors influencing creativity and innovation in producing architectural drawings through the process of observing drawings from inception to the concluding stage.

Keywords: architectural drawings, metamorphosis, perceptions, discovery

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Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

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Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Ahmed AlNouss, Salim Ahmed

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Process control refers to the techniques to control the variables in a process in order to maintain them at their desired values. Advanced process control (APC) is a broad term within the domain of control where it refers to different kinds of process control and control related tools, for example, model predictive control (MPC), statistical process control (SPC), fault detection and classification (FDC) and performance assessment. APC is often used for solving multivariable control problems and model predictive control (MPC) is one of only a few advanced control methods used successfully in industrial control applications. Advanced control is expected to bring many benefits to the plant operation; however, the extent of the benefits is plant specific and the application needs a large investment. This requires an analysis of the expected benefits before the implementation of the control. In a real plant simulation studies are carried out along with some experimentation to determine the improvement in the performance of the plant due to advanced control. In this research, such an exercise is undertaken to realize the needs of APC application. The main objectives of the paper are as follows: (1) To apply MPC to a number of simulations set up to realize the need of MPC by comparing its performance with that of proportional integral derivatives (PID) controllers. (2) To study the effect of controller parameters on control performance. (3) To develop appropriate performance index (PI) to compare the performance of different controller and develop novel idea to present tuning map of a controller. These objectives were achieved by applying PID controller and a special type of MPC which is dynamic matrix control (DMC) on the multi-tanks process simulated in loop-pro. Then the controller performance has been evaluated by changing the controller parameters. This performance was based on special indices related to the difference between set point and process variable in order to compare the both controllers. The same principle was applied for continuous stirred tank heater (CSTH) and continuous stirred tank reactor (CSTR) processes simulated in Matlab. However, in these processes some developed programs were written to evaluate the performance of the PID and MPC controllers. Finally these performance indices along with their controller parameters were plotted using special program called Sigmaplot. As a result, the improvement in the performance of the control loops was quantified using relevant indices to justify the need and importance of advanced process control. Also, it has been approved that, by using appropriate indices, predictive controller can improve the performance of the control loop significantly.

Keywords: advanced process control (APC), control loop, model predictive control (MPC), proportional integral derivatives (PID), performance indices (PI)

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Authors: Reshu Saxena, R. K. Tripathi

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HIV-1 transmission and spread involves significant host-virus interaction. Potential targets for prevention of HIV-1 lies at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and lead their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. HIV-1 Nef is important for viral infectivity and pathogenicity. It promotes HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study nef was sequenced from HIV-1 patients, and showed specific mutations revealing sequence variability in nef. To explore the difference in Nef functionality based on sequence variability we have studied the effects of HIV-1 Nef in human SupT1 T cell line and (THP-1) monocyte-macrophage cell lines through proteomics approach. 2D-Gel Electrophoresis in control and Nef-transfected SupT1 cells demonstrated several differentially expressed proteins with significant modulation of alpha-enolase. Through further studies, effects of Nef on alpha-enolase regulation were found to be cell lineage-specific, being stimulatory in macrophages/monocytes, inhibitory in T cells and without effect in HEK-293 cells. Cell migration and invasion studies were employed to determine biological function affected by Nef mediated regulation of alpha-enolase. Cell invasion was enhanced in THP-1 cells but was inhibited in SupT1 cells by wildtype nef. In addition, the modulation of enolase and cell invasion remained unaffected by a unique nef variant. These results indicated that regulation of alpha-enolase expression and invasive property of host cells by Nef is sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the suggested alpha-enolase regulating sequence of nef and a nef mutant with deletion of this site. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers, were particularly investigated by the nef mutant and peptide. Both the nef mutant and heptapeptide led to inhibition of enhanced enolase expression and increased invasiveness in THP-1 cells. Together, these findings suggest a possible mechanism of host invasion by HIV-1 through Nef mediated regulation of alpha-enolase and identifies a potential therapeutic target for HIV-1 entry at mucosal barriers.

Keywords: HIV-1 Nef, nef variants, host-virus interaction, tissue invasion

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Authors: Werner Roux Uys

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The Commissioner for the South African Revenue Service (SARS) holds a high position of trust in South African society and a lack of trust by taxpayers in the Commissioner’s actions or conduct could compromise SARS’ management of public finances. Tax morality – which is implicit in the social contract between taxpayers and the state – includes distinct phenomena that can cause a breakdown if there is a perceived lack of action on the part of the Commissioner to ensure public finances are kept safe. To promote tax morality, the Commissioner must support the judiciary in the exercise of its discretion to punish fraudulent tax activities and corrupt tax practices. For several years the political meddling in the Commissioner’s actions and conduct have caused perceived abuse of power at SARS, and taxpayers believed their hard-earned income paid over to SARS would be fruitless and wasteful expenditure. The purpose of this article is to identify and analyse previous decisions held by the South African judiciary regarding the Commissioner’s actions and conduct in tax matters, as well as consider important political statements and newspaper bulletins for the purpose of this research. The study applies a qualitative research approach and exploratory case study technique. Keywords were selected and inserted in the LexisNexis electronic database to systematically identify applicable case law where the ratio decidendi of the court referred to the actions and/or conduct of the Commissioner. Specific real-life statements, including political statements and newspaper bulletins, were selected to support the topic at hand. The purpose of the study is to educate the public about the perceptions that have transformed taxpayers’ behaviour towards the Commissioner for SARS since South Africa’s fledgling constitutional democracy was inaugurated in 1994. The study adds to the literature by identifying key characteristics or distinct phenomena regarding the actions and conduct of the Commissioner affecting taxpayers’ behaviour, including discretionary decision-making. From the findings, it emerged that SARS must abide by its (own) laws and that there is a need to educate not only South African taxpayers about tax morality, but also the public in general.

Keywords: commissioner, SARS, action and conduct, judiciary, discretionry, decsion-making

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Authors: Naira Sahakyan, Margarit Petrosyan, Armen Trchounian

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One of the tasks in contemporary biotechnology, pharmacology and other fields of human activities is to obtain biologically active substances from plants. They are very essential in the treatment of many diseases due to their actually high therapeutic value without visible side effects. However, sometimes the possibility of obtaining the metabolites is limited due to the reduction of wild-growing plants. That is why the plant cell cultures are of great interest as alternative sources of biologically active substances. Besides, during the monitored cultivation, it is possible to obtain substances that are not synthesized by plants in nature. Isolated culture of Ajuga genevensis with high growth activity and ability of regeneration was obtained using MS nutrient medium. The agar-diffusion method showed that aqueous extracts of callus culture revealed high antimicrobial activity towards various gram-positive (Bacillus subtilis A1WT; B. mesentericus WDCM 1873; Staphylococcus aureus WDCM 5233; Staph. citreus WT) and gram-negative (Escherichia coli WKPM M-17; Salmonella typhimurium TA 100) microorganisms. The broth dilution method revealed that the minimal and half maximal inhibitory concentration values against E. coli corresponded to the 70 μg/mL and 140 μg/mL concentration of the extract respectively. According to the photochemiluminescent analysis, callus tissue extracts of leaf and root origin showed higher antioxidant activity than the same quantity of A. genevensis intact plant extract. A. genevensis intact plant and callus culture extracts showed no cytotoxic effect on K-562 suspension cell line of human chronic myeloid leukemia. The GC-MS analysis showed deep differences between the qualitative and quantitative composition of callus culture and intact plant extracts. Hexacosane (11.17%); n-hexadecanoic acid (9.33%); and 2-methoxy-4-vinylphenol (4.28%) were the main components of intact plant extracts. 10-Methylnonadecane (57.0%); methoxyacetic acid, 2-tetradecyl ester (17.75%) and 1-Bromopentadecane (14.55%) were the main components of A. genevensis callus culture extracts. Obtained data indicate that callus culture of A. genevensis can be used as an alternative source of biologically active substances.

Keywords: Ajuga genevensis, antibacterial activity, antioxidant activity, callus cultures

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Authors: Philip Friedlander, John Rutledge, Jason Suh

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Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.

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

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Authors: Adebisi David Alade

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In pre-colonial West Africa, the deadliness of the climate vis-a- vis malaria and other tropical diseases to Europeans turned the region into the “white man’s grave.” Thus, immediately after the partition of Africa in 1885, civilisatrice and mise en valeur not only became a pretext for the establishment of colonial rule; from a medical point of view, the control and possible eradication of disease in the continent emerged as one of the first concerns of the European colonizers. Though geared toward making Africa exploitable, historical evidence suggests that some colonial Water, Sanitation and Hygiene (WASH) policies and projects reduced certain tropical diseases in some West African communities. Exploring some of these disease control interventions by way of historical revisionism, this paper challenges the orthodox interpretation of colonial sanitation and public health measures in West Africa. This paper critiques the deployment of race and class as analytical tools for the study of colonial WASH projects, an exercise which often reduces the complexity and ambiguity of colonialism to the binary of colonizer and the colonized. Since West Africa presently ranks high among regions with Neglected Tropical Diseases (NTDs), it is imperative to decentre colonial racism and economic exploitation in African history in order to give room for Africans to see themselves in other ways. Far from resolving the problem of NTDs by fiat in the region, this study seeks to highlight important blind spots in African colonial history in an attempt to prevent post-colonial African leaders from throwing away the baby with the bath water. As scholars researching colonial sanitation and public health in the continent rarely examine its complex meaning and content, this paper submits that the outright demonization of colonial rule across space and time continues to build ideological wall between the present and the past which not only inhibit fruitful borrowing from colonial administration of West Africa, but also prevents a wide understanding of the challenges of WASH policies and projects in most West African states.

Keywords: colonial rule, disease control, neglected tropical diseases, WASH

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