Discovery of a small molecule allosteric activator of human thiosulfate sulfurtransferase

Recent studies showed that thiosulfate sulfurtransferase (TST) is one of the few peripherally expressed genes that has been identified as a genetic risk factor for metabolic health, with clear evidence of a negative correlation with the development of obesity-related type 2 diabetes with insulin resistance2,3. Thiosulfate, a substrate for TST, is administered to diabetic mice to improve their glucose intolerance and insulin resistance, in part by increasing secretion of the insulin-sensitizing hormone adiponectin from adipocytes3T3-L12–5. In addition, hTST and its substrate, thiosulfate, have beneficial effects on hyperglycemia induced kidney damage in zebrafish embryos6. Therefore, development of effective TST activators offers the possibility to create novel antidiabetic drugs and the identification of crystal structure of human TST will help to develop it. Although a high-resolution structure of the highly homologous bovine TST is available7,8, there exist subtle changes in the amino acid composition of residues peripheral to the predicted active site cysteine in human TST

Using Value-Stream Mapping to Enhance the Production Performance in Infrastructure Construction Projects in Qatar: A Case Study

Current research on sustainable construction has primarily concentrated on the design and operation phases of projects. However, the enhancement of execution and production phases of infrastructure construction projects have received little attention. In this paper, Value Stream Mapping (VSM) is used, as a Lean production tool, to evaluate production operational waste during the project construction phase. VSM considers the development of process maps that support project managers in diagnosing the current state of production in order to propose future improvements. VSM addresses the underlying causes of issues, as opposed to the symptoms addressed by traditional tools. This paper presents a case study of the application of VSM in the construction of infrastructure projects to improve the manhole and high-density polyethylene pipe connection process. This study's primary contribution is to provide a comprehensive account of the application of VSM in the infrastructure construction industry, confirming its ability to identify the sources of production waste, quantify them, suggest reduction strategies, and develop a TAKT planning. The case study's result demonstrates an effective approach to enhance the performance of construction projects targeting to optimize the resources used and reduce costs, improve quality standards, mitigate the associated wastes and enhance the TAKT time concept in construction of deep utilities in infrastructure construction project

Digital Transformation Readiness in Infrastructure Project

Digital technologies have brought a new performance momentum in all industries and businesses wherever it has been fully adopted from manufacturing to healthcare and to climate change monitoring. In construction, the digital transformation has been limited to design phases while missing the operations part. It becomes crucial for the world's largest ecosystem to accelerate this digitalization at full scale. In infrastructure projects, digitalization is introduced to the operational level as a ready-made tool that lacks flexibility. This paper describes the barriers to the digital transition in construction operations, combined with the emerging impact of the COVID-19 pandemic from planning and progress monitoring aspects. Adoption of lean construction implementation in infrastructure projects in the State of Qatar, requires adoption for digital tools for data collection, verification, and analysis. This process is continuously improved at the project level to deliver a digital tool that is tailored to the infrastructure projects. This paper describes the initial steps for digital transformation in infrastructure projects in-line with a digital maturity growth

Choosing by Advantages (CBA) Used as a Qualitative Assessment Methodology in Lean Construction

Decision making is part of the daily duties of researchers, engineers, and consultants, and taking the right decisions requires quantitative assessment which usually needs data and analysis. In construction industry, data collection or detailed analysis are practically complicated that cannot drive the right results. This fact leads to the common use of qualitative assessment where the numbers are not available, and the evaluation involves various criteria from diverse perspectives. As a Lean tool, Choosing by Advantage (CBA) is used predominately in the Design process. This paper's characteristics and contributions to the existing body of knowledge presents the CBA practice as a qualitative assessment tool in construction phases in the Lean Construction implementation in infrastructure projects, proposing equations through the technique which determines exactly how to assess the percentage advantage for each factor for qualitative factors with different grades or different ranks. The flexibility of CBA as a multicriteria decision-analysis (MCDA) model helped overcome the differences between criteria, categories, and value-based analysis. This paper describes the experience of selecting the option that considers advantages from various criteria in an extensive assessment

Assessment of Workflow Reliability in Two Infrastructure Projects Considering Efficient Adoption of Lean Leadership Culture and Engagement

An organization leadership culture is the corner stone of success or failure. This paper focuses on Lean Leadership as an emergent concept introduced to many organizations where leaders are role models, empower their teams and make them accountable. In construction projects, culture is usually the combination of behaviours, attitudes, and communication inherited from previous experiences. A culture change is not welcomed unless mandated by the leadership and practiced daily. Where many factors are similar, two projects had different outcomes. A root cause analysis, on two infrastructure projects with the Public Works Authority ASHGHAL in the State of Qatar, reveals that project culture is the driving factor on a successful delivery on time and budget, and complying to quality, health and safety, and environment standards, with a public satisfaction focus. Client pre-set strategic objectives are achieved through a collaborative effort of project team where accountability is the bonding agent between promises and accomplishments. This paper summarizes a lean leadership culture adoption where it established a psychological safe working environment that delivers project to client expectations

IS ACROMEGALY A HYPERCOAGULABLE CONDITION? CASE REPORTS AND REVIEW OF THE LITERATURE

Introduction: Cardiovascular complications are a major cause of morbidity and mortality in patients with uncontrolled acromegaly. However, there are no published reports of an increased risk of venous thromboembolism (VTE) in such patients. We report three patients with uncontrolled acromegaly who presented with VTE. Clinical Cases: A 52-year-old male with uncontrolled acromegaly despite transsphenoidal (TSP) surgery and medical therapy presented in 2012 with acute chest pain and shortness of breath that was later con rmed as secondary to pulmonary embolism. A 44-year-old male immigrant, previously treated for acromegaly with radiation therapy alone, in 1992, in his native country, was referred to our centre in 2006 for acromegaly which remained uncontrolled despite medical therapy until 2009 when he achieved remission through TSP surgery. He had several episodes of VTE between 2008 and 2010. A 69-year-old male with uncontrolled acromegaly for 28 years despite two surgical resections and radiation therapy in 1986 and 1992, as well as continuous medical therapy, presented with VTE of the right axillary vein and bilateral pulmonary emboli in 2011. A thrombophilia screen in case 1 showed mild protein S de ciency, case 2 was homozygous for factor V Leiden (FVL) mutation and case 3 was heterozygous for FVL. Extensive investigations revealed no evidence of malignancy and echocardiography showed preserved ejection fraction in all three patients. Conclusion: Patients with uncontrolled acromegaly may be at increased risk of VTE. However, larger studies are required to further assess this association and determine the underlying cause. Key words: Acromegaly, pituitary tumours, thromboembolism

Macro-mineral concentration analysis of Acacia ehrenbergiana (Salam) from the origin of Fujairah, UAE, with staple food items as a mineral rich dietary supplement for arid and semi-arid lands of the world

Background: Acacia ehrenbergiana is native plant of the Emirates of Fujairah, UAE. It’s qualities of being salt tolerant and coping up with harsh condition makes it prime focus and one of the priority plants for the Higher authorities in Fujairah.Methods: The following study has assessed the nutritional values of Acacia ehrenbergiana and its comparison with staple foods used around the world. Proximate analyses were determined by international standard procedures (Association of Official Analytical Chemists, AOAC 2001.11, AOAC 920.39, AOAC 962.29, AOAC 942.05). Mineral ICP-OES vegetation mapping NVDI done using data from Sentinel2 satellite.Results: The study highlighted the importance of this native plant as a potential source of potassium, calcium, and magnesium with higher values of these minerals as compared to the wheat, rice, soyabean and chickpeas. Expansion of vegetation has also been mapped which provide useful insight into the potential of Fujairah’s landscape in mass production of Acacia ehrenbergiana.Conclusion: Results shows that the Acacia ehrenbergiana is agro-economically favorable plant with nutritional values similar and mineral values higher than the widely used staple food crops. Moreover, the expansion of agriculture area in Fujairah provides more hope in expanding the production of Acacia ehrenbergiana and its use on industrial level to produce food items or dietary supplement as economically viable solution to malnutrition in world.Keywords: Acacia ehrenbergiana; Priority plant; Native; Fujairah; High potassium; Calcium; Magnesium; Vegetation; Mapping; Sentinel2; NVD

An Intelligent and Low-cost Eye-tracking System for Motorized Wheelchair Control

In the 34 developed and 156 developing countries, there are about 132 million disabled people who need a wheelchair constituting 1.86% of the world population. Moreover, there are millions of people suffering from diseases related to motor disabilities, which cause inability to produce controlled movement in any of the limbs or even head.The paper proposes a system to aid people with motor disabilities by restoring their ability to move effectively and effortlessly without having to rely on others utilizing an eye-controlled electric wheelchair. The system input was images of the users eye that were processed to estimate the gaze direction and the wheelchair was moved accordingly. To accomplish such a feat, four user-specific methods were developed, implemented and tested; all of which were based on a benchmark database created by the authors.The first three techniques were automatic, employ correlation and were variants of template matching, while the last one uses convolutional neural networks (CNNs). Different metrics to quantitatively evaluate the performance of each algorithm in terms of accuracy and latency were computed and overall comparison is presented. CNN exhibited the best performance (i.e. 99.3% classification accuracy), and thus it was the model of choice for the gaze estimator, which commands the wheelchair motion. The system was evaluated carefully on 8 subjects achieving 99% accuracy in changing illumination conditions outdoor and indoor. This required modifying a motorized wheelchair to adapt it to the predictions output by the gaze estimation algorithm. The wheelchair control can bypass any decision made by the gaze estimator and immediately halt its motion with the help of an array of proximity sensors, if the measured distance goes below a well-defined safety margin.Comment: Accepted for publication in Sensor, 19 Figure, 3 Table

Investigating pharmacy students’ therapeutic decision-making with respect to antimicrobial stewardship cases

Background: Antimicrobial stewardship programs (ASPs) play a big role in minimizing antimicrobial resistance. Pharmacists are essential members of the health care team and in order for them to fulfill roles on ASP teams and become antimicrobial stewards, they must be prepared adequately by pharmacy schools prior to entry into actual practice. Although programming has been implemented into entry-to-practice programs worldwide, little is known about how students interpret antimicrobial stewardship (AMS) data and arrive at clinical decisions. We aimed to explore students’ cognitive processes and determine how they formulate therapeutic decisions when presented with AMS cases. Methods: This was a qualitative study conducted using a case study approach, in which a sample (n=20) of pharmacy students was recruited to interpret AMS cases. Semi-structured 1-on-1 interviews were arranged with each participant. A think-aloud procedure with verbal protocol analysis was adopted to determine students’ decision-making processes. Thematic analysis was used to interpret themes from the interview data. Results: Two themes were interpreted from the data: students’ focus and students’ approach to case interpretation. Students’ focus relates to external factors students consider when interpreting AMS case data and use to make and justify therapeutic decisions including patient-centered factors, drug-related factors, AMS interventions, and pharmacist’s role. Students’ clinical reasoning describes the approach that students use to interpret the data and the decision-making processes they employ to arrive at a clinical decision including a systematic approach versus non-systematic approach. Conclusions: Students vary in their focus and the cognitive strategies used to interpret AMS cases. Findings support the notion that clinical reasoning and decision-making should be explicitly taught in pharmacy curricula, in order to help students become aware of their own cognitive processes and decision-making abilities.This study was completed with funding from an Internal Student Grant from Qatar University (QUST-2-CPH-2020-9)

A synthetic peptide as an allosteric inhibitor of human arginase I and II

Arginine metabolism mediated by arginases plays a critical role in cell and tissue function. The arginine hydrolysis is deeply involved in the urea cycle, which helps the kidney excrete ammonia from blood. Upregulation of arginases affects microenvironment stability due to the presence of excess urea in blood. To regulate the arginase activities properly, a synthetic peptide based on the structure of human arginase I was designed and assessed. Preliminary data shows it inhibits human arginase I and II with an IC50 of 2.4 +/- 0.3 and 1.8 +/- 0.1 mmol, respectively. Our kinetic analysis indicates the inhibition is not competitive with substrate - suggesting an allosteric mechanism. This result provides a step towards specific inhibitors design