Predicting Solar Irradiance using Time Series Neural Networks

Increasing the accuracy of prediction improves the performance of photovoltaic systems and alleviates the effects of intermittence on the systems stability. A Nonlinear Autoregressive Network with Exogenous Inputs (NARX) approach was applied to the Vichy-Rolla National Airport\u27s photovoltaic station. The proposed model uses several inputs (e.g. time, day of the year, sky cover, pressure, and wind speed) to predict hourly solar irradiance. Data obtained from the National Solar Radiation Database (NSRDB) was used to conduct simulation experiments. These simulations validate the use of the proposed model for short-term predictions. Results show that the NARX neural network notably outperformed the other models and is better than the linear regression model. The use of additional meteorological variables, particularly sky cover, can further improve the prediction performance

Role of c-Cbl in skeletal muscle energy metabolism in relation to obesity

The obesity epidemic has already reached alarming rates in both developed and developing countries. Positive energy balance due to high calorie intake with decreased energy expenditure resulted in the current pandemic of obesity. Obesity is associated with other metabolic diseases, including type 2 diabetes (T2D). Skeletal muscle plays a major role in the control of whole-body glucose and lipid metabolism. Obese subjects have an excessive accumulation of lipid species, which interferes with the activation of insulin signaling pathways in key metabolic tissues such as the liver and skeletal muscle. Therefore, understanding the molecular mechanisms regulating energy expenditure in skeletal muscle, in particular, mitochondrial function and mitochondrial oxidative capacity has been a major research focus in obesity. It has been reported that mice lacking the c-Casitas B-lineage Lymphoma protein (c-Cbl) exhibit enhanced energy expenditure and insulin sensitivity, indicating that c-Cbl is a major factor contributing to the maintenance of whole-body energy homeostasis. c-Cbl was initially identified as an E3 ubiquitin ligase involved in the regulation of tyrosine kinase signaling. Previous studies showed that global knockout (KO) of c-Cbl in mice protects against high fat (HFat)-induced obesity and insulin resistance by increasing energy expenditure. However, this was a whole-body metabolic result and not specific to any tissue. Based on the literature review and analysis of the gaps in our current knowledge (Chapter 1), the overall aim of this thesis was established to investigate the role of c-Cbl in muscle energy metabolism. The first aim (Chapter 3) was to characterize the pathologic features and the changes of the Cbl family in different metabolic tissues during diet-induced obesity (DIO) in mice by a HFat diet. The working hypothesis was that a HFat diet would induce obesity and glucose intolerance in mice and alter Cbl expression in skeletal muscle, which may contribute to body weight gain. The first aim was addressed in C57BL/6J male mice fed a HFat diet, which induces obesity and insulin resistance. The results showed that the HFat diet induced adiposity (as indicated by more than 80% of body weight gain and a threefold increase in epididymal fat mass), glucose intolerance, lipid accumulation (increased triglycerides deposition in liver and muscle), and impaired muscle formation (suppressed myogenin expression levels). Associated with the development of metabolic syndrome, c-Cbl content was upregulated in skeletal muscle but not in the liver and white adipose tissue, and Casitas B-lineage Lymphoma protein-b (Cbl-b) was decreased in skeletal muscle by HFat-fed mice. These findings suggest that c-Cbl expression is specifically increased in skeletal muscle during HFat-induced obesity. Based on these findings the second aim (Chapter 4) was to investigate the mechanism of c-Cbl regulation in muscle mitochondrial function, mitochondrial oxidative capacity, mitochondrial biogenesis, and mitochondrial degradation. The working hypothesis was that c-Cbl knockdown (KD) may enhance muscle mitochondrial function, mitochondrial oxidative capacity and mitochondrial biogenesis and degradation in muscle cells. The second aim was addressed in the C2C12 muscle cell line by knocking down c-Cbl. Using a specific shorthairpin RNA (shRNA), expression of c-Cbl protein was reduced during muscle proliferation (myoblasts), and this reduction was maintained until muscle differentiation (myotubes). c-Cbl KD resulted in a significant increase in oxygen consumption basally and during maximal respiration in myotubes by about 20%. These data suggest that skeletal muscle is likely to be a major site of c-Cbl-mediated energy metabolism for the whole-body. We observed a significant increase in the phosphorylation of adenosine onophosphate protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in c-Cbl KD myotubes. The protein levels of mitochondrial complexes and the mitochondrial biogenesis in c-Cbl KD myotubes were increased compared with control myotubes. These findings suggest that c-Cbl KD increases the ability of energy metabolism in muscle cells. The third aim (Chapter 5) was to investigate the role of c-Cbl in muscle formation /myogenesis. The working hypothesis was that c-Cbl KD may enhance myogenesis and reduce lipid accumulation in mature muscle. This was addressed in the C2C12 muscle cell line by knocking down the expression of c-Cbl to investigate the specific effect of c-Cbl on muscle formation/myogenesis during muscle differentiation. The results determined that c-Cbl KD in myotubes enhanced myotube formation. While c-Cbl upregulation in skeletal muscle is associated with obesity, downregulation of c-Cbl promotes energy expenditure in muscle cells independent of AMPK activation. In addition, c-Cbl KD in myogenic differentiation reduced lipid accumulation under insulin-resistant conditions. These findings suggest that c-Cbl KD promotes myogenesis and may enhance insulin sensitivity. Chapter 6 summarizes the major findings and conclusions, and it discusses the limitations of studies in this thesis and how future studies could address the remaining issues and potential implications for humans. Overall, our data demonstrate that obesity affects c-Cbl expression in skeletal muscle. c-Cbl KD in mature muscle cells results in enhanced mitochondrial function. These findings suggest that c-Cbl in skeletal muscle is an important regulator of energy metabolism, and it may be targeted for the treatment of obesity and associated metabolic disorders

Analysing the critical factors influencing trust in e-government adoption from citizens’ perspective: A systematic review and a conceptual framework

Although the success adoption of e-government contingent upon citizens’ trust and their willingness to use it, little consideration has been paid to explore the adoption of e-government from citizens’ trust perspective. This paper provides a critical and systematic review of the current literature on citizens’ trust in e-government, with a particular focus on the most critical factors influencing citizens’ trust in respect of the adoption of e-government. The extant literature was identified through six electronic databases, from 2000 to 2014. Academic articles were reviewed if they contained a relevant discussion of the antecedents or factors influencing citizens’ trust in e-government adoption. The findings of this review reveal that several studies have been conducted in the area of trust in e-government (particularly trust in government and trust in the internet) with limited consideration paid to citizen's aspects of trust (such as personality, culture, gender, experience, education level, beliefs and value of systems). Based on the findings of the critical review, a conceptual framework is proposed by developing further the updated DeLone and McLean IS Success Model, which presents the antecedents of trust in e-government adoption

Room-Temperature Quantum Emitter in Aluminum Nitride

A device that is able to produce single photons is a fundamental building block for a number of quantum technologies. Significant progress has been made in engineering quantum emission in the solid state, for instance, using semiconductor quantum dots as well as defect sites in bulk and two-dimensional materials. Here we report the discovery of a room-temperature quantum emitter embedded deep within the band gap of aluminum nitride. Using spectral, polarization, and photon-counting time-resolved measurements we demonstrate bright ($>10^5$ counts per second), pure ($g^{(2)}(0) < 0.2$), and polarized room-temperature quantum light emission from color centers in this commercially important semiconductor

The role of AdipoR1 and AdipoR2 in liver fibrosis

Activation of the adiponectin (APN) signaling axis retards liver fibrosis. However, understanding of the role of AdipoR1 and AdipoR2 in mediating this response is still rudimentary. Here, we sought to elucidate the APN receptor responsible for limiting liver fibrosis by employing AdipoR1 and AdipoR2 knock-out mice in the carbon tetrachloride (CCl4) model of liver fibrosis. In addition, we knocked down receptor function in primary hepatic stellate cells (HSCs) in vitro. Following the development of fibrosis, AdipoR1 and AdipoR2 KO mice had no quantitative difference in fibrosis by Sirius red staining. However, AdipoR2 KO mice had an enhanced fibrotic signature with increased Col1-α1, TGFß-1, TIMP-1, IL-10, MMP-2 and MMP-9. Knockdown of AdipoR1 or AdipoR2 in HSCs followed by APN treatment demonstrated that AdipoR1 and AdipoR2 did not affect proliferation or TIMP-1 gene expression, while AdipoR2 modulated Col1-α1 and α-SMA gene expression, HSC migration, and AMPK activity. These finding suggest that AdipoR2 is the major APN receptor on HSCs responsible for mediating its anti-fibrotic effects

Identification of FDA-approved drugs against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through computational virtual screening

The SARS-CoV-2 coronavirus is responsible for the COVID-19 outbreak, which overwhelmed millions of people worldwide; hence, there is an urgency to identify appropriate antiviral drugs. This study focuses on screening compounds that inhibit RNA-dependent RNA-polymerase (RdRp) essential for RNA synthesis required for replication of positive-strand RNA viruses. Computational screening against RdRp using Food and Drug Administration (FDA)-approved drugs identified ten prominent compounds with binding energies of more than − 10.00 kcal/mol, each a potential inhibitor of RdRp. These compounds’ binding energy is comparable to known RdRp inhibitors remdesivir (IC50 = 10.09 μM, SI = 4.96) and molnupiravir (EC50 = 0.67 − 2.66 µM) and 0.32–2.03 µM). Remdesivir and molnupiravir have been tested in clinical trial and remain authorized for emergency use in the treatment of COVID-19. In docking simulations, selected compounds are bound to the substrate-binding pocket of RdRp and showed hydrophobic and hydrogen bond interaction. For molecular dynamics simulation, capmatinib, pralsetinib, ponatinib, and tedizolid phosphate were selected from the initial ten candidate compounds. MD simulation indicated that these compounds are stable at 50-ns MD simulation when bound to RdRp protein. The screen hit compounds, remdesivir, molnupiravir, and GS-441524, are bound in the substrate binding pocket with good binding-free energy. As a consequence, capmatinib, pralsetinib, ponatinib, and tedizolid phosphate are potential new inhibitors of RdRp protein with potential of limiting COVID-19 infection by blocking RNA synthesis

Limited Impact of the Protein Corona on the Cellular Uptake of PEGylated Zein Micelles by Melanoma Cancer Cells

The formation of a protein layer corona on the nanoparticle surface upon entry into a biological environment was shown to strongly influence the interactions with cells, especially affecting the uptake of nanomedicines. In this work, we present the impact of the protein corona on the uptake of PEGylated zein micelles by cancer cells, macrophages, and dendritic cells. Zein was successfully conjugated with poly(ethylene glycol) (PEG) of varying chain lengths (5K and 10K) and assembled into micelles. Our results demonstrate that PEGylation conferred stealth effects to the zein micelles. The presence of human plasma did not impact the uptake levels of the micelles by melanoma cancer cells, regardless of the PEG chain length used. In contrast, it decreased the uptake by macrophages and dendritic cells. These results therefore make PEGylated zein micelles promising as potential drug delivery systems for cancer therapy

Digital Citizenship And Mental And Physical Well-Being Of Saudi Citizens

Background: The escalating integration of technology and digital platforms in the lives of individuals raises pertinent concerns regarding its impact on mental and physical well-being. This study aims to explore the association between Digital Citizenship and the well-being of Saudi citizens, considering the multifaceted dimensions of digital behavior and their potential consequences. Method: Employing a cross-sectional descriptive research design, data was collected from a diverse sample of 400 healthcare workers in the Jizan Region, KSA. The Digital Citizenship Scale was utilized to assess online behaviors, while the Short Form 12 (SF-12) Questionnaire gauged mental and physical well-being. Descriptive statistics, Pearson Correlation, t-tests, and ANOVA were employed for data analysis. Results: The findings revealed a significant correlation between various facets of digital citizenship and mental and physical well-being. Responsible digital behaviors, such as online etiquette and security consciousness, correlated positively with enhanced well-being. Conversely, exposure to cyberbullying and security breaches was associated with lower well-being scores. Conclusion: The study underscores the vital role of responsible digital citizenship in shaping the mental and physical well-being of Saudi citizens. Promoting awareness and education regarding digital behaviors can contribute to a healthier online environment. Policymakers, educators, and healthcare professionals are encouraged to collaborate in integrating digital citizenship education and initiatives to safeguard the well-being of individuals in the digital age

Investigation of 5’-norcarbocyclic nucleoside analogues as antiprotozoal and antibacterial agents

Carbocyclic nucleosides have long played a role in antiviral, antiparasitic, and antibacterial therapies. Recent results from our laboratories from two structurally related scaffolds have shown promising activity against both Mycobacterium tuberculosis and several parasitic strains. As a result, a small structure activity relationship study was designed to further probe their activity and potential. Their synthesis and the results of the subsequent biological activity are reported herein

Kabuki Syndrome with Chiari malformation type II: A case report

Kabuki syndrome is a rare genetic disorder, characterized by typical facial features, hypotonia, developmental delay and intellectual disabilities. We report here a Saudi female infant diagnosed as a case of Kabuki syndrome clinically and confirmed by molecular genetic testing. She was admitted at birth to neonatal ICU due to hydrocephalus and meningomyelocele and found to have Chiari malformation type II on radiological evaluation of the brain. Whole exome sequencing (WES) was sent for her and showed pathogenic variant in KDM6A which confirm the diagnosis of Kabuki syndrome