Search results for: Iman Sharifi

Authors: Iman Shabanzadeh

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Earthquake is known as one of the most frequent natural hazards in Iran. Therefore, policy making to improve the strengthening of structures is one of the requirements of the approach to prevent and reduce the risk of the destructive effects of earthquakes. In order to choose the optimal policy in the face of earthquakes, this article tries to examine the cost of financial damages caused by earthquakes in the building sector and compare it with the costs of retrofitting. In this study, the results of adopting the scenario of "action after the earthquake" and the policy scenario of "strengthening structures before the earthquake" have been collected, calculated and finally analyzed by putting them together. Methodologically, data received from governorates and building retrofitting engineering companies have been used. The scope of the study is earthquakes occurred in the geographical area of Iran, and among them, eight earthquakes have been specifically studied: Miane, Ahar and Haris, Qator, Momor, Khorasan, Damghan and Shahroud, Gohran, Hormozgan and Ezgole. The main basis of the calculations is the data obtained from retrofitting companies regarding the cost per square meter of building retrofitting and the data of the governorate regarding the power of earthquake destruction, the realized costs for the reconstruction and construction of residential units. The estimated costs have been converted to the value of 2021 using the time value of money method to enable comparison and aggregation. The cost-benefit comparison of the two policies of action after the earthquake and retrofitting before the earthquake in the eight earthquakes investigated shows that the country has suffered five thousand billion Tomans of losses due to the lack of retrofitting of buildings against earthquakes. Based on the data of the Budget Law's of Iran, this figure was approximately twice the budget of the Ministry of Roads and Urban Development and five times the budget of the Islamic Revolution Housing Foundation in 2021. The results show that the policy of retrofitting structures before an earthquake is significantly more optimal than the competing scenario. The comparison of the two policy scenarios examined in this study shows that the policy of retrofitting buildings before an earthquake, on the one hand, prevents huge losses, and on the other hand, by increasing the number of earthquake-resistant houses, it reduces the amount of earthquake destruction. In addition to other positive effects of retrofitting, such as the reduction of mortality due to earthquake resistance of buildings and the reduction of other economic and social effects caused by earthquakes. These are things that can prove the cost-effectiveness of the policy scenario of "strengthening structures before earthquakes" in Iran.

Keywords: disaster economy, earthquake economy, cost-benefit analysis, resilience

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Authors: Abdullah S. Alghamdi, Khaled Alghamdi, Richard O. Jenkins, Parvez I. Haris

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Background: Physical activity is an important factor in the treatment and prevention of type 2 diabetes mellitus (T2DM). Reduction in HbA1c level, an important diabetes biomarker, was reported in patients who increased their daily physical activity. Although the ambient temperature was reported to be positively correlated to a negative impact on health and increase the incidences of diabetes, the exposure to bright sunlight was recently found to be associated with enhanced insulin sensitivity and improved beta-cell function. How Ramadan alters physical activity, and especially sunlight exposure, has not been adequately investigated. Aim: This study aimed to assess the physical activity and sun exposure of Saudis with T2DM over different periods (before, during, and after Ramadan) and related this to HbA1c levels. Methods: This study recruited 82 Saudis with T2DM, who chose to fast during Ramadan, from the Endocrine and Diabetic Centre of Al Iman General Hospital, Riyadh, Saudi Arabia. Ethical approvals for this study were obtained from De Montfort University and Saudi Ministry of Health. Physical activity and sun exposure were assessed by a self-administered questionnaire. Physical activity was estimated using the International Physical Activity Questionnaire (IPAQ), while the sun exposure was assessed by asking the patients about their hours per week of direct exposure to the sun, and daily hours spent outdoors. Blood samples were collected in each period for measuring HbA1c. Results: Low physical activity was observed in more than 60% of the patients, with no significant changes between periods. There were no significant variances between periods in the daily hours spent outdoors and the total number of weekly hours of direct exposure to the sun. The majority of patients reported only few hours of exposure to the sun (1h or less per week) and time spent outdoors (1h or less per day). The mean HbA1c significantly changed between periods (P = 0.001), with lowest level during Ramadan. There were significant differences in the mean HbA1c between the groups for the level of physical activity (P < 0.001), with significant lower mean HbA1c in the higher-level group. There were no significant variances in the mean of HbA1c between the groups for the daily hours spent outdoors. The mean HbA1c of the patients, who reported never in their total weekly hours of exposure to the sun, was significantly lower than the mean HbA1c of those who reported 1 hour or less (P = 0.001). Conclusion: Physical inactivity was prevalent among the study population with very little exposure to the sun or time spent outdoors. Higher level of physical activity was associated with lower mean HbA1c levels. Encouraging T2DM patients to achieve the recommended levels of physical activity may help them to obtain greater benefits of Ramadan fasting, such as reducing their HbA1c levels. The impact of low direct exposure to the sun and the time spent outdoors needs to be further investigated in both healthy and diabetic patients.

Keywords: diabetes, fasting, physical activity, sunlight, Ramadan

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Authors: Maryam Hasanali, Syed Mohammad Mojtabaei, Iman Hajirasouliha, G. Charles Clifton, James B. P. Lim

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Cold-formed steel (CFS) elements are increasingly being used as main load-bearing components in the modern construction industry, including low- to mid-rise buildings. In typical multi-storey buildings, CFS structural members act as beam-column elements since they are exposed to combined axial compression and bending actions, both in moment-resisting frames and stud wall systems. Current design specifications, including the American Iron and Steel Institute (AISI S100) and the Australian/New Zealand Standard (AS/NZS 4600), neglect the beneficial effects of warping-restrained boundary conditions in the design of beam-column elements. Furthermore, while a non-linear relationship governs the interaction of axial compression and bending, the combined effect of these actions is taken into account through a simplified linear expression combining pure axial and flexural strengths. This paper aims to evaluate the reliability of the well-known Direct Strength Method (DSM) as well as design proposals found in the literature to provide a better understanding of the efficiency of the code-prescribed linear interaction equation in the strength predictions of CFS beam columns and the effects of warping-restrained boundary conditions on their behavior. To this end, the experimentally validated finite element (FE) models of CFS elements under compression and bending were developed in ABAQUS software, which accounts for both non-linear material properties and geometric imperfections. The validated models were then used for a comprehensive parametric study containing 270 FE models, covering a wide range of key design parameters, such as length (i.e., 0.5, 1.5, and 3 m), thickness (i.e., 1, 2, and 4 mm) and cross-sectional dimensions under ten different load eccentricity levels. The results of this parametric study demonstrated that using the DSM led to the most conservative strength predictions for beam-column members by up to 55%, depending on the element’s length and thickness. This can be sourced by the errors associated with (i) the absence of warping-restrained boundary condition effects, (ii) equations for the calculations of buckling loads, and (iii) the linear interaction equation. While the influence of warping restraint is generally less than 6%, the code suggested interaction equation led to an average error of 4% to 22%, based on the element lengths. This paper highlights the need to provide more reliable design solutions for CFS beam-column elements for practical design purposes.

Keywords: beam-columns, cold-formed steel, finite element model, interaction equation, warping-restrained boundary conditions

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Authors: Afnan Al-Romi, Iman Al-Momani

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The urge of applying the Software Engineering (SE) processes is both of vital importance and a key feature in critical, complex large-scale systems, for example, safety systems, security service systems, and network systems. Inevitably, associated with this are risks, such as system vulnerabilities and security threats. The probability of those risks increases in unsecured environments, such as wireless networks in general and in Wireless Sensor Networks (WSNs) in particular. WSN is a self-organizing network of sensor nodes connected by wireless links. WSNs consist of hundreds to thousands of low-power, low-cost, multi-function sensor nodes that are small in size and communicate over short-ranges. The distribution of sensor nodes in an open environment that could be unattended in addition to the resource constraints in terms of processing, storage and power, make such networks in stringent limitations such as lifetime (i.e. period of operation) and security. The importance of WSN applications that could be found in many militaries and civilian aspects has drawn the attention of many researchers to consider its security. To address this important issue and overcome one of the main challenges of WSNs, security solution systems have been developed by researchers. Those solutions are software-based network Intrusion Detection Systems (IDSs). However, it has been witnessed, that those developed IDSs are neither secure enough nor accurate to detect all malicious behaviours of attacks. Thus, the problem is the lack of coverage of all malicious behaviours in proposed IDSs, leading to unpleasant results, such as delays in the detection process, low detection accuracy, or even worse, leading to detection failure, as illustrated in the previous studies. Also, another problem is energy consumption in WSNs caused by IDS. So, in other words, not all requirements are implemented then traced. Moreover, neither all requirements are identified nor satisfied, as for some requirements have been compromised. The drawbacks in the current IDS are due to not following structured software development processes by researches and developers when developing IDS. Consequently, they resulted in inadequate requirement management, process, validation, and verification of requirements quality. Unfortunately, WSN and SE research communities have been mostly impermeable to each other. Integrating SE and WSNs is a real subject that will be expanded as technology evolves and spreads in industrial applications. Therefore, this paper will study the importance of Requirement Engineering when developing IDSs. Also, it will study a set of existed IDSs and illustrate the absence of Requirement Engineering and its effect. Then conclusions are drawn in regard of applying requirement engineering to systems to deliver the required functionalities, with respect to operational constraints, within an acceptable level of performance, accuracy and reliability.

Keywords: software engineering, requirement engineering, Intrusion Detection System, IDS, Wireless Sensor Networks, WSN

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Authors: Abdullah S. Alghamdi, Khaled Alghamdi, Richard O. Jenkins, Parvez I. Haris

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Background: Unhealthy diet is one of the modifiable risk factors for developing type 2 diabetes mellitus (T2DM). Improvement in diet can be beneficial for countering diabetes. For example, HbA1c, an important biomarker for diabetes, can be reduced by 1.1% through only alteration in diet. Ramadan fasting has been reported to provide positive health benefits. However, optimal benefits are not achieved, often due to poor dietary habits and lifestyle. There is a need to better understand the dietary habits of people fasting during Ramadan, so that necessary improvements can be made to develop this form of fasting as a non-pharmacological strategy for management and prevention of T2DM. Aim: This study aimed to assess the dietary patterns of Saudi adult patients with T2DM over three different periods (before, during, and after Ramadan) and relate this to HbA1c levels. Methods: This study recruited 82 Saudi with T2DM, who chose to fast during Ramadan, from the Endocrine and Diabetic Centre of Al Iman General Hospital, Riyadh, Saudi Arabia. Ethical approvals for the study were obtained from De Montfort University and Saudi Ministry of Health. Dietary patterns were assessed by a self-administered questionnaire in each period. This assessment included the diet type and frequency. Blood samples were collected in each period for determination of HbA1c. Results: The number of meals per day for the participants significantly decreased during Ramadan (P < 0.001). The consumption of fruit and vegetables significantly increased during Ramadan (P = 0.017). However, the consumption of sugary drinks significantly increased during and after Ramadan (P = 0.005). Approximately 60% of the patients indicated that they ate sugary foods at least once per week. The consumption of bread and rice was reported to be at least two times per week. The consumption of rice significantly reduced during Ramadan (P = 0.002). The mean HbA1c significantly varied between periods (P = 0.001), with lowest level during Ramadan compared to before and after Ramadan. The increase in the consumption of fruits and vegetables had a medium effect size on the reduction in HbA1c during Ramadan. There was a variance of 7.7% in the mean difference in HbA1c levels between groups (who changed their fruit and vegetable consumption) which can be accounted for by the increase in the consumption of fruits and vegetables. Likewise, 9.3% of the variance in the mean HbA1c difference between the groups was accounted for by a decrease in the consumption of rice. Conclusion: The increase in the frequency of fruit and vegetables intake, and especially the reduction in the frequency of rice consumption, during Ramadan produce beneficial effects in reducing HbA1c level. Therefore, further improving the dietary habits of patients with T2DM, such as reducing their sugary drinks intake, may help them to obtain greater benefits from Ramadan fasting in the management of their diabetes. It is recommended that dietary guidance is provided to the public to maximise health benefits through Ramadan fasting.

Keywords: Diabetes, Diet, Fasting, HbA1c, Ramadan

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Authors: Shamsa Al Sharji, Athar Al Jabri, Haitham Al Dughaishi, Mirfat Al Barwani, Raja Al Rawahi, Raiya Al Rajhi, Shurooq Al Ruqaishi, Thamreen Al Zadjali, Iman Al Humaidi

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Background: External Ventricular Drains (EVDs) are critical in managing traumatic brain injuries and hydrocephalus by controlling intracranial pressure, but they carry a high risk of infection. Infection rates vary globally, ranging from 5% to 45%, leading to increased morbidity, prolonged hospital stays, and higher healthcare costs. Nursing protocols play a pivotal role in reducing these infection rates. This study investigates the impact of a structured nursing protocol on EVD-associated infections in adult neurosurgery patients at the Directorate General of Khoula Hospital, Oman, from January to September 2024. Methods: A cluster-randomized trial was conducted across neurosurgery wards and the ICU. The intervention group followed a comprehensive nursing protocol, including strict sterile insertion, standardized dressing changes, infection control training, and regular clinical audits. The control group received standard care. The primary outcome was the incidence of EVD-associated infections, with secondary outcomes including protocol compliance, infection severity, recovery times, length of stay, and 30-day mortality. Statistical analysis was conducted using Chi-square tests, paired t-tests, and logistic regression to assess the differences between groups. Results: The study involved 75 patients, with an overall infection rate of 13.3%. The intervention group showed a reduced infection rate of 8.9% compared to 20% in the control group. Compliance rates for key nursing actions were high, with 89.7% for hand hygiene and 86.2% for wound dressing. The relative risk of infection was 0.44 in the intervention group, reflecting a 55.6% reduction. Logistic regression identified obesity as a significant predictor of EVD infections. Although mortality rates were slightly higher in the intervention group, the number needed to treat (NNT) of 9 suggests that the nursing protocol may improve survival outcomes. Conclusion: This study demonstrates that structured nursing protocols can reduce EVD-related infections and improve patient outcomes in neurosurgery. While the findings are promising, further research with larger sample sizes is needed to confirm these results and optimize infection control strategies in neurosurgical care.

Keywords: EVD, CSF, nursing protocol, EVD infection

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Authors: Iman Janghorban Esfahani

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Due to the increased use of irrigation in agriculture, the importance and need for highly reliable water pumping systems have significantly increased. The pumping of the groundwater is essential to provide water for both drip and furrow irrigation to increase the agricultural yield, especially in arid regions that suffer from scarcities of surface water. The most common irrigation pumping systems (IPS) consume conventional energies through the use of electric motors and generators or connecting to the electricity grid. Due to the shortage and transportation difficulties of fossil fuels, and unreliable access to the electricity grid, especially in the rural areas, and the adverse environmental impacts of fossil fuel usage, such as greenhouse gas (GHG) emissions, the need for renewable energy sources such as photovoltaic systems (PVS) as an alternative way of powering irrigation pumping systems is urgent. Integration of the photovoltaic systems with irrigation pumping systems as the Photovoltaic Powered-Irrigation Pumping System (PVP-IPS) can avoid fossil fuel dependency and the subsequent greenhouse gas emissions, as well as ultimately lower energy costs and improve efficiency, which made PVP-IPS systems as an environmentally and economically efficient solution for agriculture irrigation in every region. The greatest problem faced by integration of PVP with IPS systems is matching the intermittence of the energy supply with the dynamic water demand. The best solution to overcome the intermittence is to incorporate a storage system into the PVP-IPS to provide water-on-demand as a highly reliable stand-alone irrigation pumping system. The water storage tank (WST) is the most common storage device for PVP-IPS systems. In the integrated PVP-IPS with a water storage tank (PVP-IPS-WST), a water storage tank stores the water pumped by the IPS in excess of the water demand and then delivers it when demands are high. The Freshwater pinch analysis (FWaPA) as an alternative to mathematical modeling was used by other researchers for retrofitting the off-grid battery less photovoltaic-powered reverse osmosis system. However, the Freshwater pinch analysis has not been used to integrate the photovoltaic systems with irrigation pumping system with water storage tanks. In this study, FWaPA graphical and numerical tools were used for retrofitting an existing PVP-IPS system located in Salahadin, Republic of Iraq. The plant includes a 5 kW submersible water pump and 7.5 kW solar PV system. The Freshwater Composite Curve as the graphical tool and Freashwater Storage Cascade Table as the numerical tool were constructed to determine the minimum required outsourced water during operation, optimal amount of delivered electricity to the water pump, and optimal size of the water storage tank for one-year operation data. The results of implementing the FWaPA on the case study show that the PVP-IPS system with a WST as the reliable system can reduce outsourced water by 95.41% compare to the PVP-IPS system without storage tank.

Keywords: irrigation, photovoltaic, pinch analysis, pumping, solar energy

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Authors: Iman Zafarparandeh, Muzammil Mumtaz, Paniz Taherzadeh, Deniz Erbulut

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The instability in the atlantoaxial joint may occur due to cervical surgery, congenital anomalies, and trauma. There are different types of fixation techniques proposed for restoring the stability and preventing harmful neurological deterioration. Application of the screw constructs has become a popular alternative to the older techniques for stabilizing the joint. The main difference between the various screw constructs is the type of the screw which can be lateral mass screw, pedicle screw, transarticular screw, and translaminar screw. The aim of this paper is to study the effect of three popular screw constructs fixation techniques on the biomechanics of the atlantoaxial joint using the finite element (FE) method. A three-dimensional FE model of the upper cervical spine including the skull, C1 and C2 vertebrae, and groups of the existing ligaments were developed. The accurate geometry of the model was obtained from the CT data of a 35-year old male. Three screw constructs were designed to compare; Magerl transarticular screw (TA-Screw), Goel-Harms lateral mass screw and pedicle screw (LM-Screw and Pedicle-Screw), and Wright lateral mass screw and translaminar screw (LM-Screw and TL-Screw). Pure moments were applied to the model in the three main planes; flexion (Flex), extension (Ext), axial rotation (AR) and lateral bending (LB). The range of motion (ROM) of C0-C1 and C1-C2 segments for the implanted FE models are compared to the intact FE model and the in vitro study of Panjabi (1988). The Magerl technique showed less effect on the ROM of C0-C1 than the other two techniques in sagittal plane. In lateral bending and axial rotation, the Goel-Harms and Wright techniques showed less effect on the ROM of C0-C1 than the Magerl technique. The Magerl technique has the highest fusion rate as 99% in all loading directions for the C1-C2 segment. The Wright technique has the lowest fusion rate in LB as 79%. The three techniques resulted in the same fusion rate in extension loading as 99%. The maximum stress for the Magerl technique is the lowest in all load direction compared to other two techniques. The maximum stress in all direction was 234 Mpa and occurred in flexion with the Wright technique. The maximum stress for the Goel-Harms and Wright techniques occurred in lateral mass screw. The ROM obtained from the FE results support this idea that the fusion rate of the Magerl is more than 99%. Moreover, the maximum stress occurred in each screw constructs proves the less failure possibility for the Magerl technique. Another advantage of the Magerl technique is the less number of components compared to other techniques using screw constructs. Despite the benefits of the Magerl technique, there are drawbacks to using this method such as reduction of the C1 and C2 before screw placement. Therefore, other fixation methods such as Goel-Harms and Wright techniques find the solution for the drawbacks of the Magerl technique by adding screws separately to C1 and C2. The FE model implanted with the Wright technique showed the highest maximum stress almost in all load direction.

Keywords: cervical spine, finite element model, atlantoaxial, fixation technique

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Authors: Mohammad Ehsani, Iman Zarei, Soudabeh Moazemigoudarzi

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The aim of this study is to determine Pro-Environmental Behavioral Intention of Mountain Hikers to the Theory of Planned Behavior. According to many researchers nature-based recreation activities play a significant role in the tourism industry and have provided myriad opportunities for the protection of natural areas. It is essential to investigate individuals' behavior during such activities to avoid further damage to precious and dwindling natural resources. This study develops a robust model that provides a comprehensive understanding of the formation of pro-environmental behavioral intentions among climbers of Mount Damavand National Park in Iran. To this end, we combined the theory of planned behavior (TPB), value-belief-norm theory (VBN), and a hierarchical model of leisure constraints to predict individuals’ pro-environmental hiking behavior during outdoor recreation. It was used structural equation modeling to test the theoretical framework. A sample of 787 climbers was analyzed. Among the theory of planned behavior variables, perceived behavioral control showed the strongest association with behavioral intention (β = .57). This relationship indicates that if people feel they can have fewer negative impacts on national resources while hiking, it will result in more environmentally acceptable behavior. Subjective norms had a moderate positive impact on behavioral intention, indicating the importance of other people on the individual's behavior. Attitude had a small positive effect on intention. Ecological worldview positively influenced attitude and personal belief. Personal belief (awareness of consequences and ascribed responsibility) showed a positive association with TPB variables. Although the data showed a high average score in awareness of consequences (mean = 4.219 out of 5), evidence from Damavand Mount shows that there are many environmental issues that need addressing (e.g., vast amounts of garbage). National park managers need to make sure that their solutions result in awareness about proenvironmental behavior (PEB). Findings showed that negative relationship between constraints and all TPB predictors. Providing proper restrooms and parking spaces in campgrounds, strategies controlling limiting capacity and solutions for removing waste from high altitudes are helpful to decrease the negative impact of structural constraints. In order to address intrapersonal constraints, managers should provide opportunities to interest individuals in environmental activities, such as environmental celebrations or making documentaries about environmental issues. Moreover, promoting a culture of environmental protection in the Damavand Mount area would reduce interpersonal constraints. Overall, the proposed model improved the explanatory power of the TPB by predicting 64.7% of intention compared to the original TPB that accounted for 63.8% of the variance in intention.

Keywords: theory of planned behavior, pro-environmental behavior, national park, constraints

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Authors: Abdullah S. Alghamdi, Khaled Alghamdi, Richard O. Jenkins, Parvez I. Haris

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Background: Quantity and quality of sleep have been reported to be significant risk factors for obesity and development of metabolic disorders such as type 2 diabetes mellitus (T2DM). The relationship between diabetes and sleep quantity was reported to be U-shaped, which means increased or decreased sleeping hours can increase the risk of diabetes. The plasma glucagon levels were found to continuously decrease during night-time sleep in healthy individuals, independently of blood glucose and insulin levels. The disturbance of the circadian rhythm is also important and has been linked with an increased the chance of diabetes incidence. There is a lack of research on sleep patterns on Saudis with T2DM and how this is affected by Ramadan fasting. Aim: To assess the sleeping patterns of Saudis with T2DM (before, during, and after Ramadan), using two different techniques and relate this to their HbA1c levels. Method: This study recruited 82 Saudi with T2DM, who chose to fast during Ramadan, from the Endocrine and Diabetic Centre of Al Iman General Hospital, Riyadh, Saudi Arabia. Ethical approvals for the study were obtained from De Montfort University and Saudi Ministry of Health. Their sleeping patterns were assessed by a self-administered questionnaire (before, during, and after Ramadan). The assessment included the daily total sleeping hours (DTSH), and total night-time sleeping hours (TNTSH) of the participants. In addition, sleeping patterns of 36 patients, randomly selected from the 82 participants, were further tracked during and after Ramadan by using Fitbit Flex 2™ accelerometer. Blood samples were collected in each period for measuring HbA1c. Results: Questionnaire analysis revealed that the sleeping patterns significantly changed between the periods, with shorter hours during Ramadan (P < 0.001 for DTSH, and P < 0.001 for TNTSH). These findings were confirmed by the Fitbit data, which also indicated significant shorter sleeping hours for the DTSH, and the TNTSH during Ramadan (P < 0.001 and P < 0.001, respectively). Although there were no significant correlations between the questionnaire and Fitbit data, the TNTSH were shorter among the participants in all periods by both techniques. The mean HbA1c significantly varied between periods, with lowest level during Ramadan. Although the statistical tests did not show significant variances in the mean HbA1c between the groups of participants regarding their hours of sleeping, the lowest mean HbA1c was observed in the group of participants who slept for 6-8 hours and had longer night-time sleeping hours. Conclusion: A short sleep duration, and absence of night-time sleep were significantly observed among the majority of the study population during Ramadan, which could suppress the full benefits of Ramadan fasting for diabetic patients. This study showed that there is a good agreement between the findings of the questionnaire and the Fitbit device for evaluating sleeping patterns in a Saudi population. A larger study is needed in the future to investigate the impact of Ramadan fasting on sleep quality and quantity and its relationship with health and disease.

Keywords: Diabetes, Fasting, Fitbit, HbA1c, IPAQ, Ramadan, Sleep

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Authors: Iman Farasat, Howard M. Salis

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Engineered genetic circuits reprogram cellular behavior to act as living computers with applications in detecting cancer, creating self-controlling artificial tissues, and dynamically regulating metabolic pathways. Phenemenological models are often used to simulate and design genetic circuit behavior towards a desired behavior. While such models assume that each circuit component’s function is modular and independent, even small changes in a circuit (e.g. a new promoter, a change in transcription factor expression level, or even a new media) can have significant effects on the circuit’s function. Here, we use statistical thermodynamics to account for the several factors that control transcriptional regulation in bacteria, and experimentally demonstrate the model’s accuracy across 825 measurements in several genetic contexts and hosts. We then employ our first principles model to design, experimentally construct, and characterize a family of signal amplifying genetic circuits (genetic OpAmps) that expand the dynamic range of cell sensors. To develop these models, we needed a new approach to measuring the in vivo binding free energies of transcription factors (TFs), a key ingredient of statistical thermodynamic models of gene regulation. We developed a new high-throughput assay to measure RNA polymerase and TF binding free energies, requiring the construction and characterization of only a few constructs and data analysis (Figure 1A). We experimentally verified the assay on 6 TetR-homolog repressors and a CRISPR/dCas9 guide RNA. We found that our binding free energy measurements quantitatively explains why changing TF expression levels alters circuit function. Altogether, by combining these measurements with our biophysical model of translation (the RBS Calculator) as well as other measurements (Figure 1B), our model can account for changes in TF binding sites, TF expression levels, circuit copy number, host genome size, and host growth rate (Figure 1C). Model predictions correctly accounted for how these 8 factors control a promoter’s transcription rate (Figure 1D). Using the model, we developed a design framework for engineering multi-promoter genetic circuits that greatly reduces the number of degrees of freedom (8 factors per promoter) to a single dimensionless unit. We propose the Ptashne (Pt) number to encapsulate the 8 co-dependent factors that control transcriptional regulation into a single number. Therefore, a single number controls a promoter’s output rather than these 8 co-dependent factors, and designing a genetic circuit with N promoters requires specification of only N Pt numbers. We demonstrate how to design genetic circuits in Pt number space by constructing and characterizing 15 2-repressor OpAmp circuits that act as signal amplifiers when within an optimal Pt region. We experimentally show that OpAmp circuits using different TFs and TF expression levels will only amplify the dynamic range of input signals when their corresponding Pt numbers are within the optimal region. Thus, the use of the Pt number greatly simplifies the genetic circuit design, particularly important as circuits employ more TFs to perform increasingly complex functions.

Keywords: transcription factor, synthetic biology, genetic circuit, biophysical model, binding energy measurement

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