Deep learning-based recognition system for pashto handwritten text: benchmark on PHTI.

This article introduces a recognition system for handwritten text in the Pashto language, representing the first attempt to establish a baseline system using the Pashto Handwritten Text Imagebase (PHTI) dataset. Initially, the PHTI dataset underwent pre-processed to eliminate unwanted characters, subsequently, the dataset was divided into training 70%, validation 15%, and test sets 15%. The proposed recognition system is based on multi-dimensional long short-term memory (MD-LSTM) networks. A comprehensive empirical analysis was conducted to determine the optimal parameters for the proposed MD-LSTM architecture; Counter experiments were used to evaluate the performance of the proposed system comparing with the state-of-the-art models on the PHTI dataset. The novelty of our proposed model, compared to other state of the art models, lies in its hidden layer size (i.e., 10, 20, 80) and its Tanh layer size (i.e., 20, 40). The system achieves a Character Error Rate (CER) of 20.77% as a baseline on the test set. The top 20 confusions are reported to check the performance and limitations of the proposed model. The results highlight complications and future perspective of the Pashto language towards the digital transition.

Synthesis of new class of indole acetic acid sulfonate derivatives as ectonucleotidases inhibitors.

Ectonucleotidases inhibitors (ENPPs, e5'NT (CD73) and h-TNAP) are potential therapeutic candidates for the treatment of cancer. Adenosine, the cancer-developing, and growth moiety is the resultant product of these enzymes. The synthesis of small molecules that can increase the acidic and ionizable structure of adenosine 5-monophosphate (AMP) has been used in traditional attempts to inhibit ENPPs, ecto-5'-nucleotidase and h-TNAP. In this article, we present a short and interesting method for developing substituted indole acetic acid sulfonate derivatives (5a-5o), which are non-nucleotide based small molecules, and investigated their inhibitory potential against recombinant h-ENPP1, h-ENPP3, h-TNAP, h-e5'NT and r-e5'NT. Their overexpression in the tumor environment leads to high adenosine level that results in tumor development as well as immune evasion. Therefore, selective, and potent inhibitors of these enzymes would be expected to decrease adenosine levels and manage tumor development and progression. Our intended outcome led to the discovery of new potent inhibitors like' 5e (IC50 against h-ENPP1 = 0.32 ± 0.01 µM, 58 folds increased with respect to suramin), 5j (IC50 against h-ENPP3 = 0.62 ± 0.003 µM, 21 folds increase with respect to suramin), 5c (IC50 against h-e5'NT = 0.37 ± 0.03 µM, 115 folds increase with respect to sulfamic acid), 5i (IC50 against r-e5'NT = 0.81 ± 0.05 µM, 95 folds increase with respect to sulfamic acid), and 5g (IC50 against h-TNAP = 0.59 ± 0.08 µM, 36 folds increase with respect to Levamisole). Molecular docking studies revealed that inhibitors of these selected target enzymes induced favorable interactions with the key amino acids of the active site, including Lys255, Lys278, Asn277, Gly533, Lys528, Tyr451, Phe257, Tyr340, Gln465, Gln434, Lys437, Glu830, Cys818, Asn499, Arg40, Phe417, Phe500, Asn503, Asn599, Tyr281, Arg397, Asp526, Phe419 and Tyr502. Enzyme kinetic studies revealed that potent compounds such as 5j and 5e blocked these ectonucleotidases competitively while compounds 5e and 5c presented an un-competitive binding mode. 5g revealed a non-competitive mode of inhibition.

Exploring chromone sulfonamides and sulfonylhydrazones as highly selective ectonucleotidase inhibitors: Synthesis, biological evaluation and in silico study.

Ectonucleotidases, a well-known superfamily of plasma membrane located metalloenzymes plays a central role in mediating the process of purinergic cell signaling. Major functions performed by these enzymes include the hydrolysis of extracellular nucleosides and nucleotides which are considered as important cell-signaling molecules. Any (patho)-physiologically induced disruption in this purinergic cell signaling leads to several disorders, hence these enzymes are important drug targets for therapeutic purposes. Among the major challenges faced in the design of inhibitors of ectonucleotidases, an important one is the lack of selective inhibitors. Access to highly selective inhibitors via a facile synthetic route will not only be beneficial therapeutically, but will also lead to an increase in our understanding of intricate interplay between members of ectonucleotidase enzymes in relation to their selective activation and/or inhibition in different cells and tissues. Herein we describe synthesis of highly selective inhibitors of human intestinal alkaline phosphatase (h-IAP) and human tissue non-specific alkaline phosphatase (h-TNAP), containing chromone sulfonamide and sulfonylhydrazone scaffolds. Compound 1c exhibited highest (and most selective) h-IAP inhibition activity (h-IAP IC50 = 0.51 ± 0.20 µM; h-TNAP = 36.5%) and compound 3k showed highest activity and selective inhibition against h-TNAP (h-TNAP IC50 = 1.41 ± 0.10 µM; h-IAP = 43.1%). These compounds were also evaluated against another member of ectonucleotidase family, that is rat and human ecto-5'-nucleotidase (r-e5'NT and h-e5'NT). Some of the compounds exhibited excellent inhibitory activity against ecto-5'-nucleotidase. Compound 2 g exhibited highest inhibition against h-e5'NT (IC50 = 0.18 ± 0.02 µM). To rationalize the interactions with the binding site, molecular docking studies were carried out.

Efficacy of cow and buffalo dung on vermiremediation and phytoremediation of heavy metals via Fourier-transform infrared spectroscopy and comet assay.

Heavy metal contamination raised significant concerns throughout the world. The current research aimed to evaluate the impact of organic manure (cow dung and buffalo dung) on vermiremediation and phytoremediation and to remediate heavy metals, i.e., cadmium, lead, and chromium, from artificial contaminated soil via both remediation techniques. The impact of livestock manure was evaluated for the first time which could be effective in in situ as well as ex situ studies. Eisenia fetida, Pheretima lignicola, and Spinacia oleracea were used for the remediation process. Results revealed that E. fetida tolerated lead at 280 mg, cadmium at 150 mg, and chromium at 860 mg compared to P. lignicola. The growth and reproduction of E. fetida were efficient in the cow dung manure compared to buffalo dung. Similarly, seed germination and growth of Spinacia oleracea were better in cow dung media compared to buffalo dung. Bioaccumulation factor showed that E. fetida showed a higher accumulation of heavy metals in their tissues when vermi + phytoremediation was jointly applied (9.50 mg/l of Pb, 24.166 of Cd, and 6.695 of Cr). Fourier-transform infrared spectroscopy indicated that heavy metals had no drastic effects on E. fetida and S. oleracea. Similarly, comet assay revealed that heavy metals had no genotoxic effect on the E. fetida and S. oleracea. It was concluded that both E. fetida and S. oleracea are appropriate for heavy metals remediation in cow dung manure.

Design, Synthesis, and Biological Evaluation of Novel Dihydropyridine and Pyridine Analogs as Potent Human Tissue Nonspecific Alkaline Phosphatase Inhibitors with Anticancer Activity: ROS and DNA Damage-Induced Apoptosis.

Small molecules with nitrogen-containing scaffolds have gained much attention due to their biological importance in the development of new anticancer agents. The present paper reports the synthesis of a library of new dihydropyridine and pyridine analogs with diverse pharmacophores. All compounds were tested against the human tissue nonspecific alkaline phosphatase (h-TNAP) enzyme. Most of the compounds showed excellent enzyme inhibition against h-TNAP, having IC50 values ranging from 0.49 ± 0.025 to 8.8 ± 0.53 µM, which is multi-fold higher than that of the standard inhibitor (levamisole = 22.65 ± 1.60 µM) of the h-TNAP enzyme. Furthermore, an MTT assay was carried out to evaluate cytotoxicity against the HeLa and MCF-7 cancer cell lines. Among the analogs, the most potent dihydropyridine-based compound 4d was selected to investigate pro-apoptotic behavior. The further analysis demonstrated that compound 4d played a significant role in inducing apoptosis through multiple mechanisms, including overproduction of reactive oxygen species, mitochondrial dysfunction, DNA damaging, and arrest of the cell cycle at the G1 phase by inhibiting CDK4/6. The apoptosis-inducing effect of compound 4d was studied through staining agents, microscopic, and flow cytometry techniques. Detailed structure-activity relationship (SAR) and molecular docking studies were carried out to identify the core structural features responsible for inhibiting the enzymatic activity of the h-TNAP enzyme. Moreover, fluorescence emission studies corroborated the binding interaction of compound 4d with DNA through a fluorescence titration experiment.

Network Threat Detection Using Machine/Deep Learning in SDN-Based Platforms: A Comprehensive Analysis of State-of-the-Art Solutions, Discussion, Challenges, and Future Research Direction.

A revolution in network technology has been ushered in by software defined networking (SDN), which makes it possible to control the network from a central location and provides an overview of the network's security. Despite this, SDN has a single point of failure that increases the risk of potential threats. Network intrusion detection systems (NIDS) prevent intrusions into a network and preserve the network's integrity, availability, and confidentiality. Much work has been done on NIDS but there are still improvements needed in reducing false alarms and increasing threat detection accuracy. Recently advanced approaches such as deep learning (DL) and machine learning (ML) have been implemented in SDN-based NIDS to overcome the security issues within a network. In the first part of this survey paper, we offer an introduction to the NIDS theory, as well as recent research that has been conducted on the topic. After that, we conduct a thorough analysis of the most recent ML- and DL-based NIDS approaches to ensure reliable identification of potential security risks. Finally, we focus on the opportunities and difficulties that lie ahead for future research on SDN-based ML and DL for NIDS.

Wireless Coexistence of Cellular LBT Systems and BLE 5.

The 2.4 GHz spectrum is home to several Radio Access Technologies (RATs), including ZigBee, Bluetooth Low Energy (BLE), and Wi-Fi. Accordingly, the technologies' spectrum-sharing qualities have been extensively studied in literature. License-Assisted Access (LAA) Listen-Before-Talk (LBT) has been identified in technical reports as the foundation for the channel access mechanism for 5G New Radio-Unlicensed (NR-U) operating in the 2.4 GHz Industrial, Scientific, and Medical (ISM) band. The introduction of NR-U into this band raises new concerns regarding coexistence of the newcomer with traditional incumbents. This article reports an investigation of BLE 5 and cellular LBT coexisting systems by means of empirical evaluation. The importance of this study stems from that the studied LBT mechanism is indicative of how 5G NR-U would perform in the 2.4 GHz band. Tests were performed in conformity with the American National Standards Institute (ANSI) C63.27 standard for evaluation of wireless coexistence, and results were reported in terms of throughput and interframe delays. In accordance with the standard and under different BLE physical layers (PHYs) and LBT priority classes, three setups were investigated. These pertain to the three tiers of evaluation, which correspond to the criticality of the device under test. Results demonstrated how BLE throughput dropped as the intended-to-unintended signal ratio decreased, and LBT classes exhibited a diminishing effect as the class priority descended. Long Range BLE PHY was found to sustain longer gap times (i.e., delay) than the other two PHYs; however, it showed less susceptibility to interference. Results also demonstrated that low data rate BLE PHYs hindered the LBT throughput performance since they correspond to longer airtime durations.

Synthesis, Characterization, and In Silico Studies of Novel Spirooxindole Derivatives as Ecto-5'-Nucleotidase Inhibitors.

Ecto-5'-nucleotidase (ecto-5'-NT, CD73) inhibitors are promising drug candidates for cancer therapy. Traditional efforts used to inhibit the ecto-5'-nucleotidase have involved antibody therapy or development of small molecule inhibitors that can mimic the acidic and ionizable structure of adenosine 5'-monophosphate (AMP). Herein, we report an efficient, environment friendly route for the synthesis of non-nucleotide based small molecules, i.e., substituted spirooxindole derivatives 9a-9l and investigated their inhibitory potential on human and rat recombinant ecto-5'-nucleotidase isozymes. These attempts have resulted in the identification of compound 9f (IC50 = 0.15 ± 0.02 µM) inhibitor on h-ecto-5'-NT which showed 280-fold higher inhibition and compound 9h (IC50 ± 0.19 ± 0.03 µM) on r-ecto-5'-NT with 406-fold enhanced inhibition than reference standard sulfamic acid. Moreover, in silico studies were carried out to assess binding interactions of potent compounds within enzyme active sites and demonstrated excellent correlation with the experimental findings.

Sulfonylhydrazones: Design, synthesis and investigation of ectonucleotidase (ALP & e5'NT) inhibition activities.

Medicinal importance of the sulfonylhydrazones is well-evident owing to their binding ability with zinc containing metalloenzymes. In the present study, we have synthesized different series of sulfonylhydrazones by using facile synthetic methods in good to excellent yield. All the successfully prepared sulfonylhydrazones were screened for ectonucleotidase (ALP & e5'NT) inhibitory activity. Among the chromen-2-one scaffold based sulfonylhydrazones, the compounds 7 was found to be most potent inhibitor for h-TNAP (human tissue non-specific alkaline phosphatase) and h-IAP (human intestinal alkaline phosphatase) with IC50 values of 1.02 ± 0.13 and 0.32 ± 0.0 3 µM respectively, compared with levamisole (IC50 = 25.2 ± 1.90 µM for h-TNAP) and l-phenylalanine (IC50 = 100 ± 3.00 µM for h-IAP) as standards. Further, the chromen-2-one based molecule 5a showed excellent activity against h-ecto 5'-NT (human ecto-5'-nucleotidase) with IC50 value of 0.29 ± 0.004 µM compared to standard, sulfamic acid (IC50 = 42.1 ± 7.8 µM). However, among the series of phenyl ring based sulfonylhydrazones, compound 9d was found to be most potent against h-TNAP and h-IAP with IC50 values of 0.85 ± 0.08 and 0.52 ± 0.03 µM, respectively. Moreover, in silico studies were also carried to demonstrate their putative binding with the target enzymes. The potent compounds 5a, 7, and 9d against different ectonucleotidases (h-ecto 5'-NT, h-TNAP, h-IAP) could potentially serve as lead for the development of new therapeutic agents.

5G NR-U: Homogeneous Coexistence Analysis.

Current technical reports indicate License-Assisted Access (LAA) Listen-Before-Talk (LBT) as the preferred channel access scheme for the upcoming 5G New Radio-Unlicensed. Various studies have examined heterogeneous coexistence of WiFi/LTE-LAA systems. This paper investigates the homogeneous coexistence of intra-network LAA-LBT devices operating in dense deployment scenarios. Results relevant to ETSI-specified priority classes are reported in terms of channel utilization, collision probability, and channel access delay. The framework presented in this paper is then employed to investigate wireless coexistence in a 5G-enabled intensive care unit employing remote patient monitoring over 5G NR-U.

Interfacial Tension of the Water-Diluted Bitumen Interface at High Bitumen Concentrations Measured Using a Microfluidic Technique.

The interfacial tension (IFT) is a critical parameter to inform our understanding of the phenomena of drop breakup and droplet-droplet coalescence in sheared water-in-diluted bitumen (dilbit) emulsions. A microfluidic extensional flow device (MEFD) was used to determine the IFT of the dilbit-water emulsion system for bitumen concentrations of 33%, 50%, and 67% by weight (solvent to bitumen ratio (S/B) = 2, 1, and 0.5, respectively) and two different pH values of water: 8.3 and 9.9. The IFT was observed to increase with the bitumen concentration and decrease significantly upon lowering the water pH. The time scale for achieving the steady state IFT increased with bitumen concentration and was less sensitive to the water pH. But the most important feature of our measurements is that the IFTs recorded were significantly smaller than the values reported in the literature. We recognized two important differences between our studies and prior investigations: measurement of the IFT of water drops in dilbit as opposed to dilbit drops in water in earlier studies, and time scales of measurement of IFT that ranged from hundreds of milliseconds to a few seconds, as compared to a minute or longer in past investigations. These differences were examined carefully, but neither was found to explain the low IFTs measured in our studies. Our work leads to the following hypothesis: the mechanical properties of the interface of a sheared water drop in bitumen are significantly different from a stagnant one.

Cholinesterase Inhibitory Activities of N-Phenylthiazol-2-Amine Derivatives and their Molecular Docking Studies.

Alzheimer's disease (AD) is a type of neurodegenerative disorder which is responsible for many cognitive dysfunctions. According to the most accepted cholinergic hypothesis, cholinesterases have a major role in AD symptoms. The use of small molecules as inhibitors is one of the most useful strategies to control AD. In the present work, a series of N-phenylthiazol-2-amine derivatives was screened against acetylcholinesterase (AChE) from Electrophorus electricus and butyrylcholinesterase (BChE) from horse serum by using Ellman's method, using neostigmine and donepezil as reference drugs. Some of the assayed compounds proved to be potent inhibitors for AChE and BChE activity. N-(2,3-dimethylphenyl)thiazol-2-amine, 3j was found to be the most active inhibitor among the series with IC50 value of 0.009 ± 0.002 µM and 0.646 ± 0.012 µM against AChE and BChE, respectively. Molecular docking studies were carried out in order to better understand the ligand binding site interactions.

Synthesis, cytotoxicity and molecular modelling studies of new phenylcinnamide derivatives as potent inhibitors of cholinesterases.

The present study reports the synthesis of cinnamide derivatives and their biological activity as inhibitors of both cholinesterases and anticancer agents. Controlled inhibition of brain acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) may slow neurodegeneration in Alzheimer's diseases (AD). The anticholinesterase activity of phenylcinnamide derivatives was determined against Electric Eel acetylcholinesterase (EeAChE) and horse serum butyrylcholinesterase (hBChE) and some of the compounds appeared as moderately potent inhibitors of EeAChE and hBChE. The compound 3-(2-(Benzyloxy)phenyl)-N-(3,4,5-trimethoxyphenyl)acrylamide (3i) showed maximum activity against EeAChE with an IC50 0.29 ± 0.21 µM whereas 3-(2-chloro-6-nitrophenyl)-N-(3,4,5-trimethoxyphenyl)acrylamide (3k) was proved to be the most potent inhibitor of hBChE having IC50 1.18 ± 1.31 µM. To better understand the enzyme-inhibitor interaction of the most active compounds toward cholinesterases, molecular modelling studies were carried out on high-resolution crystallographic structures. The anticancer effects of synthesized compounds were also evaluated against cancer cell line (lung carcinoma). The compounds may be useful leads for the design of a new class of anticancer drugs for the treatment of cancer and cholinesterase inhibitors for Alzheimer's disease (AD).

Design, synthesis, molecular docking studies and in vitro screening of ethyl 4-(3-benzoylthioureido) benzoates as urease inhibitors.

Thioureas are exceptionally versatile building blocks towards the synthesis of wide variety of heterocyclic systems, which also possess extensive range of pharmacological activities. The substituted benzoic acids were converted into corresponding acid chlorides, these acid chlorides were then treated with potassium thiocyanate in acetone and then the reaction mixture was refluxed for 1-2h afford ethyl 4-(3-benzoylthioureido)benzoates thioureas in good yields. All the newly synthesized compounds were evaluated for their urease inhibitory activities and were found to be potent inhibitors of urease enzyme. Compounds 1f and 1g were identified as the most potent urease inhibitors (IC50 0.21 and 0.13 µM, respectively), and was 100-fold more potent than the standard inhibitors. Further molecular docking studies were carried out using the crystal structure of urease to find out the binding mode of the inhibitors with the enzyme.