An Aldehyde-Driven, Fe(0)-Mediated, One-Pot Reductive Cyclization: Direct Access to 5,6-Dihydro-quinazolino[4,3-b]quinazolin-8-ones and Photophysical Study.

A short, proficient, and regioselective synthesis of biheterocyclic 5,6-dihydro-quinazolino[4,3-b]quinazolin-8-ones has been revealed via an Fe(0)-powder-mediated, one-pot reductive cyclization protocol. Mechanistic investigation proved that water acts as a source of hydrogen for the reduction of the nitro group and the reaction rate was accelerated by an aldehyde. The designed transformation works under aerobic conditions, providing a series of bio-inspired molecular scaffolds. In addition, the photophysical study showed blue fluorescence emission with a good fluorescence quantum yield.

Correlation-Based Anomaly Detection in Industrial Control Systems.

Industrial Control Systems (ICSs) were initially designed to be operated in an isolated network. However, recently, ICSs have been increasingly connected to the Internet to expand their capability, such as remote management. This interconnectivity of ICSs exposes them to cyber-attacks. At the same time, cyber-attacks in ICS networks are different compared to traditional Information Technology (IT) networks. Cyber attacks on ICSs usually involve a sequence of actions and a multitude of devices. However, current anomaly detection systems only focus on local analysis, which misses the correlation between devices and the progress of attacks over time. As a consequence, they lack an effective way to detect attacks at an entire network scale and predict possible future actions of an attack, which is of significant interest to security analysts to identify the weaknesses of their network and prevent similar attacks in the future. To address these two key issues, this paper presents a system-wide anomaly detection solution using recurrent neural networks combined with correlation analysis techniques. The proposed solution has a two-layer analysis. The first layer targets attack detection, and the second layer analyses the detected attack to predict the next possible attack actions. The main contribution of this paper is the proof of the concept implementation using two real-world ICS datasets, SWaT and Power System Attack. Moreover, we show that the proposed solution effectively detects anomalies and attacks on the scale of the entire ICS network.

Fluorinated Nucleosides: Synthesis, Modulation in Conformation and Therapeutic Application.

Over the last twenty years, fluorination on nucleoside has established itself as the most promising tool to use to get biologically active compounds that could sustain the clinical trial by affecting the pharmacodynamics and pharmacokinetic properties. Due to fluorine's inherent unique properties and its judicious introduction into the molecule, makes the corresponding nucleoside metabolically very stable, lipophilic, and opens a new site of intermolecular binding. Fluorination on various nucleosides has been extensively studied as a result, a series of fluorinated nucleosides come up for different therapeutic uses which are either approved by the FDA or under the advanced stage of the clinical trial. Here in this review, we are summarizing the latest development in the chemistry of fluorination on nucleoside that led to varieties of new analogs like carbocyclic, acyclic, and conformationally biased nucleoside and their biological properties, the influence of fluorine on conformation, oligonucleotide stability, and their use in therapeutics.

TrackInk: An IoT-Enabled Real-Time Object Tracking System in Space.

Nowadays, there is tremendous growth in the Internet of Things (IoT) applications in our everyday lives. The proliferation of smart devices, sensors technology, and the Internet makes it possible to communicate between the digital and physical world seamlessly for distributed data collection, communication, and processing of several applications dynamically. However, it is a challenging task to monitor and track objects in real-time due to the distinct characteristics of the IoT system, e.g., scalability, mobility, and resource-limited nature of the devices. In this paper, we address the significant issue of IoT object tracking in real time. We propose a system called 'TrackInk' to demonstrate our idea. TrackInk will be capable of pointing toward and taking pictures of visible satellites in the night sky, including but not limited to the International Space Station (ISS) or the moon. Data will be collected from sensors to determine the system's geographical location along with its 3D orientation, allowing for the system to be moved. Additionally, TrackInk will communicate with and send data to ThingSpeak for further cloud-based systems and data analysis. Our proposed system is lightweight, highly scalable, and performs efficiently in a resource-limited environment. We discuss a detailed system's architecture and show the performance results using a real-world hardware-based experimental setup.

Copper-Catalyzed One-Pot Synthesis of Quinazolinones from 2-Nitrobenzaldehydes with Aldehydes: Application toward the Synthesis of Natural Products.

A novel, efficient, and atom-economical approach for the construction of quinazolinones from 2-nitrobenzaldehydes has been unveiled via copper-catalyzed nitrile formation, hydrolysis, and reduction in one pot for the first time. In this reaction, urea is used as a source of nitrogen for nitrile formation, hydrazine hydrate is used for both the reduction of the nitro group and the hydrolysis of nitrile, and atmospheric oxygen is used as the sole oxidant. The method portrays a wide substrate scope with good functional group tolerances. Moreover, this method was applied for the synthesis of schizocommunin, tryptanthrin, phaitanthrin-A, phaitanthrin-B, and 8H-quinazolino[4,3-b]quinazolin-8-one.

Rapid Access to Benzimidazo[1,2-a]quinoline-Fused Isoxazoles via Pd(II)-Catalyzed Intramolecular Cross Dehydrogenative Coupling: Synthetic Versatility and Photophysical Studies.

An efficient and atom-economical palladium-catalyzed intramolecular cross dehydrogenative coupling (CDC) reaction has been developed for the construction of highly π-conjugated benzimidazo[1,2-a]quinoline-fused isoxazole scaffolds using molecular oxygen as sole oxidant. The approach portrayed wide substrate scope with good functional group tolerance and depicted a useful tool for the generation of fluorescence active compounds with high quantum yield. Synthetic versatility of the method via Fe-catalyzed reductive isoxazole ring cleavage toward pyridine, pyrimidine, pyrazole fused heteropolycyclic compounds has been showcase.

Protocol-Based and Hybrid Access Control for the IoT: Approaches and Research Opportunities.

Internet of Things (IoT) applications and services are becoming more prevalent in our everyday life. However, such an interconnected network of intelligent physical entities needs appropriate security to sensitive information. That said, the need for proper authentication and authorization is paramount. Access control is in the front line of such mechanisms. Access control determines the use of resources only to the specified and authorized users based on appropriate policy enforcement. IoT demands more sophisticated access control in terms of its usability and efficiency in protecting sensitive information. This conveys the need for access control to serve system-specific requirements and be flexibly combined with other access control approaches. In this paper, we discuss the potential for employing protocol-based and hybrid access control for IoT systems and examine how that can overcome the limitations of traditional access control mechanisms. We also focus on the key benefits and constraints of this integration. Our work further enhances the need to build hierarchical access control for large-scale IoT systems (e.g., Industrial IoT (IIoT) settings) with protocol-based and hybrid access control approaches. We, moreover, list the associated open issues to make such approaches efficient for access control in large-scale IoT systems.

Development and Progress in Sensors and Technologies for Human Emotion Recognition.

With the advancement of human-computer interaction, robotics, and especially humanoid robots, there is an increasing trend for human-to-human communications over online platforms (e.g., zoom). This has become more significant in recent years due to the Covid-19 pandemic situation. The increased use of online platforms for communication signifies the need to build efficient and more interactive human emotion recognition systems. In a human emotion recognition system, the physiological signals of human beings are collected, analyzed, and processed with the help of dedicated learning techniques and algorithms. With the proliferation of emerging technologies, e.g., the Internet of Things (IoT), future Internet, and artificial intelligence, there is a high demand for building scalable, robust, efficient, and trustworthy human recognition systems. In this paper, we present the development and progress in sensors and technologies to detect human emotions. We review the state-of-the-art sensors used for human emotion recognition and different types of activity monitoring. We present the design challenges and provide practical references of such human emotion recognition systems in the real world. Finally, we discuss the current trends in applications and explore the future research directions to address issues, e.g., scalability, security, trust, privacy, transparency, and decentralization.

Security Requirements for the Internet of Things: A Systematic Approach.

There has been a tremendous growth in the number of smart devices and their applications (e.g., smart sensors, wearable devices, smart phones, smart cars, etc.) in use in our everyday lives. This is accompanied by a new form of interconnection between the physical and digital worlds, commonly known as the Internet of Things (IoT). This is a paradigm shift, where anything and everything can be interconnected via a communication medium. In such systems, security is a prime concern and protecting the resources (e.g., applications and services) from unauthorized access needs appropriately designed security and privacy solutions. Building secure systems for the IoT can only be achieved through a thorough understanding of the particular needs of such systems. The state of the art is lacking a systematic analysis of the security requirements for the IoT. Motivated by this, in this paper, we present a systematic approach to understand the security requirements for the IoT, which will help designing secure IoT systems for the future. In developing these requirements, we provide different scenarios and outline potential threats and attacks within the IoT. Based on the characteristics of the IoT, we group the possible threats and attacks into five areas, namely communications, device/services, users, mobility and integration of resources. We then examine the existing security requirements for IoT presented in the literature and detail our approach for security requirements for the IoT. We argue that by adhering to the proposed requirements, an IoT system can be designed securely by achieving much of the promised benefits of scalability, usability, connectivity, and flexibility in a practical and comprehensive manner.

Synthesis and cytotoxic evaluation of apioarabinofuranosyl pyrimidines.

In view of the potent anticancer activity of the d-arabino-configured cytosine nucleoside (ara-C), apioarabinofuranosyl pyrimidine nucleosides were designed and synthesized from d-ribose as starting material. The synthetic strategy signifies that tosylation followed by in situ cyclization, one-pot controlled oxidative cleavage and acetylation by Pb(OAc)4 , stereoselective nucleobase condensation, inversion of hydroxyl group and uracil group converted to cytosine as the key steps. Synthesized apioarabinofuranosyl pyrimidine nucleosides were tested using breast, colon, and ovarian cancer cell lines. However, only compound 19a, 19b, and 22b have a moderate growth-suppressive effect against the luminal A breast cancer cell line MCF7.

Robustness of Deep Learning models in electrocardiogram noise detection and classification.

BACKGROUND AND OBJECTIVE: Automatic electrocardiogram (ECG) signal analysis for heart disease detection has gained significant attention due to busy lifestyles. However, ECG signals are susceptible to noise, which adversely affects the performance of ECG signal analysers. Traditional blind filtering methods use predefined noise frequency and filter order, but they alter ECG biomarkers. Several Deep Learning-based ECG noise detection and classification methods exist, but no study compares recurrent neural network (RNN) and convolutional neural network (CNN) architectures and their complexity. METHODS: This paper introduces a knowledge-based ECG filtering system using Deep Learning to classify ECG noise types and compare popular computer vision model architectures in a practical Internet of Medical Things (IoMT) framework. Experimental results demonstrate that the CNN-based ECG noise classifier outperforms the RNN-based model in terms of performance and training time. RESULTS: The study shows that AlexNet, visual geometry group (VGG), and residual network (ResNet) achieved over 70% accuracy, specificity, sensitivity, and F1 score across six datasets. VGG and ResNet performances were comparable, but VGG was more complex than ResNet, with only a 4.57% less F1 score. CONCLUSIONS: This paper introduces a Deep Learning (DL) based ECG noise classifier for a knowledge-driven ECG filtering system, offering selective filtering to reduce signal distortion. Evaluation of various CNN and RNN-based models reveals VGG and Resnet outperform. Further, the VGG model is superior in terms of performance. But Resnet performs comparably to VGG with less model complexity.

Synthesis of benzimidazole fused poly-heterocycles via oxidant free Cu-catalyzed dehydrogenative C-N coupling and photophysical studies.

A unique example of Cu-catalysed synthesis of benzimidazole fused poly-heterocycles via intramolecular C-N coupling reaction has been reported. The method highlights the potential of Cu-catalysed reactions via C-N bond formation in the absence of ligand, oxidant, and additives under inert atmosphere. The mechanistic studies indicate that the reaction is facilitated by the involvement of a benzimidazole N-atom and releases H2 gas, resulting in the synthesis of benzimidazole-fused coupling products in good yield. The versatility of the approach is demonstrated by the synthesis of diverse fused compounds, which exhibit high fluorescence activity and good quantum yield.

Design, synthesis and cytotoxic evaluation of truncated 3'-deoxy- 3', 3' difluororibofuranosyl pyrimidine nucleosides.

Truncated 3'-deoxy- 3', 3' difluororibofuranosyl pyrimidine nucleoside derivatives were synthesized from d-ribose via ß-apioribo pyrimidine nucleoside intermediates 11a-c. The synthetic approach signifies that truncation at C3' position of apioribose ring of 13a-c by oxidative cleavage of diols with Pb(OAc)4 and followed by fluorination with DAST as key steps. Cytotoxic evaluation of synthesized truncated nucleoside derivatives 16a-c and 19a-c were tested against MCF7 and MDA-MB-231 breast cancer cell lines. However, only 19a was shown minimal growth suppression activity on MDA-MB-231 cancer cell lines.

Structure-activity relationships of truncated adenosine derivatives as highly potent and selective human A3 adenosine receptor antagonists.

On the basis of potent and selective binding affinity of truncated 4'-thioadenosine derivatives at the human A(3) adenosine receptor (AR), their bioisosteric 4'-oxo derivatives were designed and synthesized from commercially available 2,3-O-isopropylidene-D-erythrono lactone. The derivatives tested in AR binding assays were substituted at the C2 and N(6) positions. All synthesized nucleosides exhibited potent and selective binding affinity at the human A(3) AR. They were less potent than the corresponding 4'-thio analogues, but showed still selective to other subtypes. The 2-Cl series generally were better than the 2-H series in view of binding affinity and selectivity. Among compounds tested, compound 5d (X=Cl, R=3-bromobenzyl) showed the highest binding affinity (K(i)=13.0+/-6.9 nM) at the hA(3) AR with high selectivity (at least 88-fold) in comparison to other AR subtypes. Like the corresponding truncated 4'-thio series, compound 5d antagonized the action of an agonist to inhibit forskolin-stimulated adenylate cyclase in hA(3) AR-expressing CHO cells. Although the 4'-oxo series were less potent than the 4'-thio series, this class of human A(3) AR antagonists is also regarded as another good template for the design of A(3) AR antagonists and for further drug development.

Structure-activity relationships of 2-chloro-N6-substituted-4'-thioadenosine-5'-N,N-dialkyluronamides as human A3 adenosine receptor antagonists.

On the basis of potent and selective A(3) adenosine receptor (AR) antagonist, 2-chloro-N(6)-(3-iodobenzyl)-4'-thioadenosine-5'-N,N-dimethyluronamide, structure-activity relationships were studied for a series of 5'-N,N-dialkyluronamide derivatives, synthesized from D-gulonic gamma-lactone. From this study, it was revealed that removal of the hydrogen bond-donating ability of the 5'-uronamide was essential for the pure A(3)AR antagonism. 5'-N,N-Dimethyluronamide derivatives exhibited higher binding affinity than larger 5'-N,N-dialkyl or 5'-N,N-cycloalkylamide derivatives, indicating that steric factors are crucial in binding to the human A(3)AR. A N(6)-(3-bromobenzyl) derivative 6c (K(i)=9.32 nM) exhibited the highest binding affinity at the human A(3)AR with very low binding affinities to other AR subtypes.

Synthesis and Anticancer Properties of Novel Truncated Carbocyclic Nucleoside Analogues.

BACKGROUND: Modified nucleosides established a prime role as therapeutic drugs. OBJECTIVE: Design and synthesis of novel truncated carbocyclic nucleoside with modified nucleobases and evaluation of their anticancer properties. METHODS: Novel truncated carbocyclic nucleoside analogues were synthesized from a versatile starting material D-ribose. The synthetic route includes stereoselective Grignard reaction, Wittig olefination, ring closing metathesis, double bond hydrogenation and Mitsunobu nucleobase condensation as the key steps. Cytotoxicity was measured using MTT assay in breast cancer cell lines (MCF7 and MDA-MB-231), ovarian cancer cell lines (IGROV1 and OVCAR8). RESULT & CONCLUSION: The synthesized compounds were characterized using spectroscopy techniques. The synthesized compounds induced cytotoxicity in breast cancer cell lines (MCF7 and MDA-MB-231), ovarian cancer cell lines (IGROV1 and OVCAR8) while minimal effect on primary cell line. Among the eight analogues, 1b and 1d showed the highest cytotoxicity effect and induced autophagy mode of cell death. These compounds induced autophagy by inactivating AKT and mTOR pathway. In addition, PARP1 was found to be stabilized upon treatment with compound 1b and 1d and is one of the known markers associated with induction of autophagy through the AMPK/mTOR pathway after DNA damage. Taken together, these results suggest that compounds 1b and 1d inhibit cancer cell proliferation through mTOR inactivation-mediated induction of autophagy.

Synthesis and antitumor activity of fluorocyclopentenyl-pyrimidines.

Synthesis of fluorocyclopentenyl pyrimidine nucleosides 6-9 was enantiopurely accomplished employing oxidative rearrangement, RCM reaction and electrophilic fluorination starting from d-ribose. Cytosine analog 8 was found to exhibit significant anticancer activity in various human tumor cell lines.

Stereoselective synthesis of homo-apioneplanocin A as potential inhibitor of S-adenosylhomocysteine hydrolase.

Homo-apioneplanocin A (1) as a potential inhibitor of S-adenosylhomocysteine hydrolase was synthesized from D-ribose, employing stereoselective hydroxymethylation, regioselective oxidation, and regio- and chemoselective hydroboration as key steps.

A common and versatile synthetic route to (-) and (+) pentenomycin I, (+) halopentenomycin I and dehydropentenomycin.

A versatile and stereoselective total synthesis of (+) and (-) pentenomycin I, (+) halopentenomycins I and dehydropentenomycin from a common chiral polyhydroxylated cyclopentene through oxidation and protection/deprotection has been described. Stereoselective hydroxymethylation, stereoselective Grignard reaction and ring closing metathesis are the key features of our approach.

Cycloaddition of cyclohexa-2,4-dienones with electron deficient 2 pi partners: a novel and stereoselective route to functionalized bicyclo[2.2.2]octenones.

A novel route to functionalised bicyclo[2.2.2]octenones via pi 4s + pi 2s cycloaddition of cyclohexa-2,4-dienones with electron deficient 2 pi partners, and crystal structure of 1,7-dimethyl-5-hydroxy-5-chloromethyl-2-carboethoxy bicyclo[2.2.2]oct-7-ene-6-one, is reported.