DeHiDe: Deep Learning-based Hybrid Model to Detect Fake News using Blockchain

The surge in the spread of misleading information, lies, propaganda, and false facts, frequently known as fake news, raised questions concerning social media's influence in today's fast-moving democratic society. The widespread and rapid dissemination of fake news cost us in many ways. For example, individual or societal costs by hampering elections integrity, significant economic losses by impacting stock markets, or increases the risk to national security. It is challenging to overcome the spreading of fake news problems in traditional centralized systems. However, Blockchain-- a distributed decentralized technology that ensures data provenance, authenticity, and traceability by providing a transparent, immutable, and verifiable transaction records can help in detecting and contending fake news. This paper proposes a novel hybrid model DeHiDe: Deep Learning-based Hybrid Model to Detect Fake News using Blockchain. The DeHiDe is a blockchain-based framework for legitimate news sharing by filtering out the fake news. It combines the benefit of blockchain with an intelligent deep learning model to reinforce robustness and accuracy in combating fake news's hurdle. It also compares the proposed method to existing state-of-the-art methods. The DeHiDe is expected to outperform state-of-the-art approaches in terms of services, features, and performance.Comment: 13 Pages, 5 figures, and 1 tabl

Studies on drug-DNA complexes, adriamycin-d-(TGATCA)<SUB>2</SUB> and 4'-epiadriamycin-d-(CGATCG)<SUB>2</SUB>, by phosphorus-31 nuclear magnetic resonance spectroscopy

The complexes of adriamycin-d-(TGATCA)2 and 4'-epiadriamycin-d-(CGATCG)2 are studied by one- and two-dimensional 31P nuclear magnetic resonance spectroscopy (NMR) at 500 MHz in the temperature range 275-328 K and as a function of drug to DNA ratio (0.0-2.0). The binding of drug to DNA is clearly evident in 31P-31P exchange NOESY spectra that shows two sets of resonances in slow chemical exchange. The phosphate resonances at the intercalating steps, T1pG2/C1pG2 and C5pA6/C5pG6, shift downfield up to 1.7 ppm and that at the adjacent step shift downfield up to 0.7 ppm, whereas the central phosphate A3pT4 is relatively unaffected. The variations of chemical shift with drug to DNA ratio and temperature as well as linewidths are different in each of the two complexes. These observations reflect change in population of BI/BII conformation, stretching of backbone torsional angle &#950;, and distortions in O-P-O bond angles that occur on binding of drug to DNA. To the best of our knowledge, there are no solution studies on 4'-epiadriamycin, a better tolerated drug, and binding of daunomycin or its analogue to d-(TGATCA)2 hexamer sequence. The studies report the use of 31P NMR as a tool to differentiate various complexes. The specific differences may well be the reasons that are responsible for different antitumor action of these drugs due to different binding ability and distortions in DNA

Traffic Incident Duration Prediction using BERT Representation of Text

Owing to the diverse nature of traffic incidents, accepting and storing relevant data in the form of natural language is more convenient than in constrained value fields. Textual information in such cases can be rich enough for traffic incident analysis and modelling even in the absence of certain fixed set of parameters. However limited studies considered the complexity in processing such information to predict traffic incident duration. In this paper, we propose to represent the textual data from incident reports using BERT word embeddings. These text representations are then inputted into various regressors such as LSTM, XGBoost, RF and SVR to predict traffic incident duration. To demonstrate the significance of this approach, the method is compared with the state-of-the-art approach using LDA representation. Dataset used for the experiment is the Caltrans Performance Measurement System (PeMS). Result analysis indicates that the BERT- LSTM hybrid model is effective in capturing the contextual meaning of textual incident reports to predict the traffic incident duration and outperforms LDA topic modelling with MAE around 11.16 minutes. © 2021 IEEE

Structural elucidation of 4'-epiadriamycin by nuclear magnetic resonance spectroscopy and comparison with adriamycin and daunomycin using quantum mechanical and restrained molecular dynamics approach

The structural and electronic properties of 4'-epiadriamycin, adriamycin, and daunomycin have been studied using density functional theory (DFT) employing B3LYP exchange correlation. The chemical shifts of 1H and 13C resonances in nuclear magnetic resonance spectra have been calculated using Gauge-Invariant Atomic Orbital (GIAO) method as implemented in Gaussian 98 and compared with experimental spectra recorded at 500 MHz. 13C resonances of drugs have been assigned for the first time. A restrained molecular dynamics approach was used to get the optimized solution structure of drugs using inter-proton distance constraints obtained from 2D NOESY spectra. The glycosidic angle C7-O7-C1'-C2' is found to show considerable flexibility by adopting 156&#176;-161&#176; (I), 142&#176;-143&#176; (II), and 38&#176;-78&#176; (III) conformations, of which the biological relevant structure appears to be the conformer II. The observed different conformations of the three drugs are correlated to the differential anticancer activity and the available biochemical evidence exhibited by these drugs

The Major G‑Quadruplex Formed in the Human BCL‑2 Proximal Promoter Adopts a Parallel Structure with a 13-nt Loop in K⁺ Solution

The human BCL-2 gene contains a 39-bp GC-rich region upstream of the P1 promoter that has been shown to be critically involved in the regulation of BCL-2 gene expression. Inhibition of BCL-2 expression can decrease cellular proliferation and enhance the efficacy of chemotherapy. Here we report the major G-quadruplex formed in the Pu39 G-rich strand in this BCL-2 promoter region. The 1245G4 quadruplex adopts a parallel structure with one 13-nt and two 1-nt chain-reversal loops. The 1245G4 quadruplex involves four nonsuccessive G-runs, I, II, IV, V, unlike the previously reported bcl2 MidG4 quadruplex formed on the central four G-runs. The parallel 1245G4 quadruplex with the 13-nt loop, unexpectedly, appears to be more stable than the mixed parallel/antiparallel MidG4. Parallel-stranded structures with two 1-nt loops and one variable-length middle loop are found to be prevalent in the promoter G-quadruplexes; the variable middle loop is suggested to determine the specific overall structure and potential ligand recognition site. A limit of 7 nt in loop length is used in all quadruplex-predicting software. Thus, the formation and high stability of the 1245G4 quadruplex with a 13-nt loop is significant. The presence of two distinct interchangeable G-quadruplexes in the overlapping region of the BCL-2 promoter is intriguing, suggesting a novel mechanism for gene transcriptional regulation and ligand modulation

The Major G‑Quadruplex Formed in the Human Platelet-Derived Growth Factor Receptor β Promoter Adopts a Novel Broken-Strand Structure in K⁺ Solution

Overexpression of platelet-derived growth factor receptor β (PDGFR-β) has been associated with cancers and vascular and fibrotic disorders. PDGFR-β has become an attractive target for the treatment of cancers and fibrotic disorders. DNA G-quadruplexes formed in the GC-rich nuclease hypersensitivity element of the human PDGFR-β gene promoter have been found to inhibit PDGFR-β transcriptional activity. Here we determined the major G-quadruplex formed in the PDGFR-β promoter. Instead of using four continuous runs with three or more guanines, this G-quadruplex adopts a novel folding with a broken G-strand to form a primarily parallel-stranded intramolecular structure with three 1 nucleotide (nt) double-chain-reversal loops and one additional lateral loop. The novel folding of the PDGFR-β promoter G-quadruplex emphasizes the robustness of parallel-stranded structural motifs with a 1 nt loop. Considering recent progress on G-quadruplexes formed in gene-promoter sequences, we suggest the 1 nt looped G_<i>i</i>NG_<i>j</i> motif may have been evolutionarily selected to serve as a stable foundation upon which the promoter G-quadruplexes can build. The novel folding of the PDGFR-β promoter G-quadruplex may be attractive for small-molecule drugs that specifically target this secondary structure and modulate PDGFR-β gene expression

Insight into the Complexity of the i‑Motif and G‑Quadruplex DNA Structures Formed in the <i>KRAS</i> Promoter and Subsequent Drug-Induced Gene Repression

Activating <i>KRAS</i> mutations frequently occur in pancreatic, colorectal, and lung adenocarcinomas. While many attempts have been made to target oncogenic KRAS, no clinically useful therapies currently exist. Most efforts to target KRAS have focused on inhibiting the mutant protein; a less explored approach involves targeting KRAS at the transcriptional level. The promoter element of the <i>KRAS</i> gene contains a GC-rich nuclease hypersensitive site with three potential DNA secondary structure-forming regions. These are referred to as the Near-, Mid-, and Far-regions, on the basis of their proximity to the transcription start site. As a result of transcription-induced negative superhelicity, these regions can open up to form unique DNA secondary structures: G-quadruplexes on the G-rich strand and i-motifs on the C-rich strand. While the G-quadruplexes have been well characterized, the i-motifs have not been investigated as thoroughly. Here we show that the i-motif that forms in the C-rich Mid-region is the most stable and exists in a dynamic equilibrium with a hybrid i-motif/hairpin species and an unfolded hairpin species. The transcription factor heterogeneous nuclear ribonucleoprotein K (hnRNP K) was found to bind selectively to the i-motif species and to positively modulate <i>KRAS</i> transcription. Additionally, we identified a benzophenanthridine alkaloid that dissipates the hairpin species and destabilizes the interaction of hnRNP K with the Mid-region i-motif. This same compound stabilizes the three existing <i>KRAS</i> G-quadruplexes. The combined effect of the compound on the Mid-region i-motif and the G-quadruplexes leads to downregulation of <i>KRAS</i> gene expression. This dual i-motif/G-quadruplex-interactive compound presents a new mechanism to modulate gene expression

Structure-Guided Synthesis and Mechanistic Studies Reveal Sweetspots on Naphthyl Salicyl Hydrazone Scaffold as Non-Nucleosidic Competitive, Reversible Inhibitors of Human Ribonucleotide Reductase

Ribonucleotide reductase (RR), an established cancer target, is usually inhibited by antimetabolites, which display multiple cross-reactive effects. Recently, we discovered a naphthyl salicyl acyl hydrazone-based inhibitor (<b>NSAH</b> or <i>E</i>-<b>3a</b>) of human RR (hRR) binding at the catalytic site (C-site) and inhibiting hRR reversibly. We herein report the synthesis and biochemical characterization of 25 distinct analogs. We designed each analog through docking to the C-site of hRR based on our 2.7 Å X-ray crystal structure (PDB ID: 5TUS). Broad tolerance to minor structural variations preserving inhibitory potency is observed. <i>E</i>-<b>3f</b> (82% yield) displayed an <i>in vitro</i> IC₅₀ of 5.3 ± 1.8 μM against hRR, making it the most potent in this series. Kinetic assays reveal that <i>E</i>-<b>3a</b>, <i>E</i>-<b>3c</b>, <i>E</i>-<b>3t</b>, and <i>E</i>-<b>3w</b> bind and inhibit hRR through a reversible and competitive mode. Target selectivity toward the R1 subunit of hRR is established, providing a novel way of inhibition of this crucial enzyme

The Dynamic Character of the <i>BCL2</i> Promoter i‑Motif Provides a Mechanism for Modulation of Gene Expression by Compounds That Bind Selectively to the Alternative DNA Hairpin Structure

It is generally accepted that DNA predominantly exists in duplex form in cells. However, under torsional stress imposed by active transcription, DNA can assume nonduplex structures. The <i>BCL2</i> promoter region forms two different secondary DNA structures on opposite strands called the G-quadruplex and the i-motif. The i-motif is a highly dynamic structure that exists in equilibrium with a flexible hairpin species. Here we identify a pregnanol derivative and a class of piperidine derivatives that differentially modulate gene expression by stabilizing either the i-motif or the flexible hairpin species. Stabilization of the i-motif structure results in significant upregulation of the <i>BCL2</i> gene and associated protein expression; in contrast, stabilization of the flexible hairpin species lowers <i>BCL2</i> levels. The <i>BCL2</i> levels reduced by the hairpin-binding compound led to chemosensitization to etoposide in both in vitro and in vivo models. Furthermore, we show antagonism between the two classes of compounds in solution and in cells. For the first time, our results demonstrate the principle of small molecule targeting of i-motif structures in vitro and in vivo to modulate gene expression