Genome-wide Mapping of Topoisomerase Binding Sites Suggests Topoisomerase 3α (TOP3A) as a Reader of Transcription-Replication Conflicts (TRC).

Both transcription and replication can take place simultaneously on the same DNA template, potentially leading to transcription-replication conflicts (TRCs) and topological problems. Here we asked which topoisomerase(s) is/are the best candidate(s) for sensing TRC. Genome-wide topoisomerase binding sites were mapped in parallel for all the nuclear topoisomerases (TOP1, TOP2A, TOP2B, TOP3A and TOP3B). To increase the signal to noise ratio (SNR), we used ectopic expression of those topoisomerases in H293 cells followed by a modified CUT&Tag method. Although each topoisomerase showed distinct binding patterns, all topoisomerase binding signals positively correlated with gene transcription. TOP3A binding signals were suppressed by DNA replication inhibition. This was also observed but to a lesser extent for TOP2A and TOP2B. Hence, we propose the involvement of TOP3A in sensing both head-on TRCs (HO-TRCs) and co-directional TRCs (CD-TRCs). In which case, the TOP3A signals appear concentrated within the promoters and first 20 kb regions of the 5' -end of genes, suggesting the prevalence of TRCs and the recruitment of TOP3A in the 5'-regions of transcribed and replicated genes.

Acute non-immune hemolytic anemia in enteric fever due to nalidixic acid-resistant Salmonella enterica serotype Typhi: A case report.

Nalidixic acid-resistant Salmonella enterica serotype Typhi is a well-known cause of enteric fever, and its prevalence is increasing worldwide. However, the incidence of enteric fever complicated by non-immune hemolytic anemia without co-existing thalassemia or glucose-6-phosphate dehydrogenase deficiency is rare. In this case report, we present a case of acute non-immune hemolytic anemia in enteric fever caused by nalidixic acid-resistant Salmonella enterica serotype Typhi.

Primary antiphospholipid syndrome in a male presents with acute digital ischemia: Dramatic response to glucocorticoid.

We present a rare case of primary antiphospholipid syndrome in a 38-year-old male who presented with painful digital ischemia. Early initiation of anticoagulation and addition of glucocorticoid led to a significant improvement in the patient.

Factors associated with child and maternal dietary diversity in the urban areas of Bangladesh.

Dietary diversity is an indicator of nutrition that has been found positively associated with diet quality, micronutrient adequacy, and improved maternal health and child growth. Due to the cultural responsibility of women in providing food at the household level, their status is very important to perform this role. Hence, this study has been conducted on the status of dietary diversity of the mother and child to understand how it relates to various factors of women in urban settings. Data were obtained from 1978 mother-child pairs living in different cities in Bangladesh. The foods taken by the women and children were categorized into 10 and 7 groups to measure women's dietary diversity (WDD) and children's dietary diversity (CDD), respectively. The study found that more than three-fourths of the mothers and half of the children had low dietary diversity. The household wealth holdings and access to resources by the women were found inadequate, while two-thirds of them had the lowest to medium level of nutritional knowledge. The binomial logistic regression model was used to measure the factors influencing WDD and CDD. The findings also indicated that children's dietary diversity was influenced by the mother's age, education, supportive attitude and behavior of husband, and access to and control over resources. While the household wealth index can enhance both child and mother's dietary variety, nutrition knowledge, dietary counseling, and access to and control over resources can improve maternal dietary diversity. This study recommends improving women's socioeconomic status by increasing their wealth and access to resources and enhancing their nutrition knowledge by providing food and nutrition counseling.

Effects of healthcare spending on public health status: An empirical investigation from Bangladesh.

The escalation of healthcare spending in many nations, particularly in emerging countries such as Bangladesh, may be largely attributed to the growing demand for healthcare services. Evidently, there has been a significant expansion in the public funding allocated to the health sector in Bangladesh, intending to enhance health outcomes. Therefore, the purpose of this study was to examine the impact of healthcare expenditure on health outcomes, specifically focusing on the reduction in different mortality rates and the transmission of various infectious diseases. A total of 30 years of data (1990-2019) on the health sector of Bangladesh were collected from different national and international sources. The Vector Autoregression with Exogenous Variables (VARX) model was employed to determine the effects of healthcare expenditure on health outcomes. Results revealed that the per capita health expenditure and the number of doctors showed a significant positive impact on life expectancy and maternal and child health. Also, the government's annual budget on the health sector and number of doctors had a significant positive impact on lowering deaths by Diphtheria, Cholera, Tuberculosis, and Malaria diseases. In order to develop a sustainable healthcare system within the nation, it is imperative for the government to prioritize the allocation of sufficient and effective healthcare funding to cater to the needs of the populace.

Electrochemical and computational insights into the utilization of 2, 2- dithio bisbenzothiazole as a sustainable corrosion inhibitor for mild steel in low pH medium.

Industries today place a high premium on environmentally friendly supplies that may effectively inhibit metal dissolution at a reasonable cost. Hence, in this paper, we assessed the corrosion inhibition effectiveness of the Thiazole derivative namely, 2, 2-Dithio Bisbenzothiazole (DBBT) against mild steel (MS) corrosion in 1 M HCl. Several experimental approaches, including gravimetric analysis, potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), and surface exploration using scanning electron/atomic force microscopy (SEM/AFM) and contact angle (CA), were utilized to conduct the measurements. In 1 M HCl corrosive medium at 298 K in the subsistence of 800 ppm of DBBT, this experiment indicated DBBT as an environment-friendly and sustainable corrosion inhibitor (CI) for MS, demonstrating an inhibition efficiency (IE %) of 97.71%. To deliver a deeper knowledge of the mechanism behind inhibitive behavior, the calculated thermodynamic and activation characteristics were applied. The calculated Gibbs free energy values indicated that the CI interacted physically and chemically with the MS surface, validating physio-chemical adsorption. The findings of the EIS research revealed that an upsurge in the doses of the CI is escorted by an upsurge in polarization resistance (Rp) from (88.05 → 504.04) Ωcm2, and a diminution in double layer capacitance (Cdl) from (97.46 → 46.33) µFcm-2 at (50 → 800) ppm respectively, affirming the inhibitive potential of DBBT. Additionally, the greatest displacement in Ecorr value being 76.13 mV < 85 mV, indicating that DBBT act as a mixed-form CI. To study the further impacts of DBBT on the inhibition capabilities of the compound under investigation, density functional theory (DFT) and molecular dynamics (MD) simulation were employed. Chemical and electrochemical approaches are in agreement with the computational analysis indicating DBBT is the most efficient CI.

Rare Guest-Induced Electrical Conductivity of Zn-Porphyrin Metallacage Inclusion Complexes Featuring π-Donor/Acceptor/Donor Stacks.

Charge-transfer (CT) interactions between co-facially aligned π-donor/acceptor (π-D/A) arrays engender unique optical and electronic properties that could benefit (supra)molecular electronics and energy technologies. Herein, we demonstrate that a tetragonal prismatic metal-organic cage (MOC18+) having two parallel π-donor tetrakis(4-carboxyphenyl)-Zn-porphyrin (ZnTCPP) faces selectively intercalate planar π-acceptor guests, such as hexaazatriphenylene hexacarbonitrile (HATHCN), hexacyanotriphenylene (HCTP), and napthanelediimide (NDI) derivatives, forming 1:1 πA@MOC18+ inclusion complexes featuring supramolecular π-D/A/D triads. The π-acidity of intercalated π-acceptors (HATHCN ≫ HCTP ≈ NDIs) dictated the nature and strength of their interactions with the ZnTCPP faces, which in turn influenced the binding affinities (Ka) and optical and electronic properties of corresponding πA@MOC18+ inclusion complexes. Owing to its strongest CT interaction with ZnTCPP faces, the most π-acidic HATHCN guest enjoyed the largest Ka (5 × 106 M-1), competitively displaced weaker π-acceptors from the MOC18+ cavity, and generated the highest electrical conductivity (2.1 × 10-6 S/m) among the πA@MOC18+ inclusion complexes. This work demonstrates a unique through-space charge transport capability of πA@MOC18+ inclusion complexes featuring supramolecular π-D/A/D triads, which generated tunable electrical conductivity, which is a rare but much coveted electronic property of such supramolecular assemblies that could further expand their utility in future technologies.

Enhancing drug delivery with supramolecular amphiphilic macrocycle nanoparticles: selective targeting of CDK4/6 inhibitor palbociclib to melanoma.

Drug delivery systems based on amphiphilic supramolecular macrocycles have garnered increased attention over the past two decades due to their ability to successfully formulate nanoparticles. Macrocyclic (MC) materials can self-assemble at lower concentrations without the need for surfactants and polymers, but surfactants are required to form and stabilize nanoparticles at higher concentrations. Using MCs to deliver both hydrophilic and hydrophobic guest molecules is advantageous. We developed two novel types of amphiphilic macrocycle nanoparticles (MC NPs) capable of delivering either Nile Red (NR) (a hydrophobic model) or Rhodamine B (RhB) (a hydrophilic model) fluorescent dyes. We extensively characterized the materials using various techniques to determine size, morphology, stability, hemolysis, fluorescence, loading efficiency (LE), and loading capacity (LC). We then loaded the CDK4/6 inhibitor Palbociclib (Palb) into both MC NPs using a solvent diffusion method. This yielded Palb-MC NPs in the size range of 65-90 nm. They exhibited high stability over time and in fetal bovine serum with negligible toxicity against erythrocytes. Cytotoxicity was minimal when tested against RAW macrophages, human fibroblast HDFn, and adipose stromal cells (ASCs) at higher concentrations of MC NPs. Cell viability studies were conducted with different concentrations of MC NPs, Palb-MC NPs, and free Palb against RAW macrophages, human U-87 GBM, and human M14 melanoma cell lines in vitro. Flow cytometry experiments revealed that blank MC NPs and Palb-MC NPs were selectively targeted to melanoma cells, resulting in cell death compared to the other two cell lines. Future work will focus on studying the biological effect of MC NPs including their binding affinity with molecules/receptors expressed on the M14 and other melanoma cell surfaces by molecular docking simulations. Subsequently, we will evaluate the MCs as a component of combination therapy in a murine melanoma model.

Enhancing Drug Delivery with Supramolecular Amphiphilic Macrocycle Nanoparticles: Selective Targeting of CDK4/6 Inhibitor Palbociclib to Melanoma.

Drug delivery systems based on amphiphilic supramolecular macrocycles have garnered increased attention over the past two decades due to their ability to successfully formulate nanoparticles. Macrocyclic (MC) materials can self-assemble at lower concentrations without the need for surfactants and polymers, but surfactants are required to form and stabilize nanoparticles at higher concentrations. Using MCs to deliver both hydrophilic and hydrophobic guest molecules is advantageous. We developed two novel types of amphiphilic macrocycle nanoparticles (MC NPs) capable of delivering either Nile Red (NR) (a hydrophobic model) or Rhodamine B (RhB) (a hydrophilic model) fluorescent dyes. We extensively characterized the materials using various techniques to determine size, morphology, stability, hemolysis, fluorescence, loading efficiency (LE), and loading capacity (LC). We then loaded the CDK4/6 inhibitor Palbociclib (Palb) into both MC NPs using a solvent diffusion method. This yielded Palb-MC NPs in the size range of 65-90 nm. They exhibited high stability over time and in fetal bovine serum with negligible toxicity against erythrocytes. Cytotoxicity was minimal when tested against RAW macrophages, human fibroblast HDFn , and adipose stromal cells (ASCs) at higher concentrations of MC NPs. Cell viability studies were conducted with different concentrations of MC NPs, Palb-MC NPs, and free Palb against RAW macrophages, human U-87 GBM, and human M14 melanoma cell lines in vitro. Flow cytometry experiments revealed that blank MC NPs and Palb-MC NPs were selectively targeted to melanoma cells, resulting in cell death compared to the other two cell lines. Future work will focus on studying the biological effect of MC NPs including their binding affinity with molecules/receptors expressed on the M14 and other melanoma cell surface by molecular docking simulations. Subsequently, we will evaluate the MCs as a component of combination therapy in a murine melanoma model.

From a Collapse-Prone, Insulating Ni-MOF-74 Analogue to Crystalline, Porous, and Electrically Conducting PEDOT@MOF Composites.

Electrically conductive porous metal-organic frameworks (MOFs) show great promise in helping advance electronics and clean energy technologies. However, large porosity usually hinders long-range charge transport, an essential criterion of electrical conductivity, underscoring the need for new strategies to combine these two opposing features and realize their diverse potentials. All previous strategies to boost the conductivity of porous MOFs by introducing redox-complementary guest molecules, conducting polymers, and metal nanoparticles have led to a significant loss of frameworks' porosity and surface areas, which could be otherwise exploited to capture additional guests in electrocatalysis and chemiresistive sensing applications. Herein, we demonstrate for the first time that the in situ oxidative polymerization of preloaded 3,4-ethylenedioxythiophene (EDOT) monomers into the polyethylenedioxythiophene (PEDOT) polymer inside the hexagonal cavities of an intrinsically insulating Ni2(NDISA) MOF-74 analogue (NDISA = naphthalenediimide N,N-disalicylate), which easily collapses and becomes amorphous upon drying, simultaneously enhanced the crystallinity, porosity, and electrical conductivity of the resulting PEDOT@Ni2(NDISA) composites. At lower PEDOT loading (∼22 wt %), not only did the Brunauer-Emmett-Teller surface area of the PEDOT@Ni2(NDISA) composite (926 m2/g) more than double from that of evacuated pristine Ni2(NDISA) (387 m2/g), but also its electrical conductivity (1.1 × 10-5 S/cm) soared 105 times from that of the pristine MOF, demonstrating unprecedented dual benefits of our strategy. At higher PEDOT loading (≥33 wt %), the electrical conductivity of Ni2(NDISA)⊃PEDOT composites further increased modestly (10-4 S/cm), but their porosity dropped precipitously as large amounts of PEDOT filled up the hexagonal MOF channels. Thus, our work presents a simple new strategy to simultaneously boost the structural stability, porosity, and electrical conductivity of intrinsically insulating and collapse-prone MOFs by introducing small amounts of conducting polymers that can not only reinforce the MOF scaffolds and prevent them from collapsing but also help create a much coveted non-native property by providing charge carriers and charge transport pathways.

The TDRD3-USP9X complex and MIB1 regulate TOP3B homeostasis and prevent deleterious TOP3B cleavage complexes.

TOP3B is stabilized by TDRD3. Hypothesizing that TDRD3 recruits a deubiquitinase, we find that TOP3B interacts with USP9X via TDRD3. Inactivation of USP9X destabilizes TOP3B, and depletion of both TDRD3 and USP9X does not promote further TOP3B ubiquitylation. Additionally, we observe that MIB1 mediates the ubiquitylation and proteasomal degradation of TOP3B by directly interacting with TOP3B independently of TDRD3. Combined depletion of USP9X, TDRD3 and MIB1 causes no additional increase in TOP3B levels compared to MIB1 knockdown alone indicating that the TDRD3-USP9X complex works downstream of MIB1. To comprehend why cells degrade TOP3B in the absence of TDRD3, we measured TOP3Bccs. Lack of TDRD3 increases TOP3Bccs in DNA and RNA, and induced R-loops, γH2AX and growth defect. Biochemical experiments confirm that TDRD3 increases the turnover of TOP3B. Our work provides molecular insights into the mechanisms by which TDRD3 protect cells from deleterious TOP3Bccs which are otherwise removed by TRIM41.

Generation of simulated data for Bengali text localization in natural images.

In the domain of vision-based applications, the importance of text cannot be underestimated due to its natural capacity to provide accurate and comprehensive information. The application of scene text editing systems enables the modification and enhancement of textual material included in natural images while maintaining the integrity of the overall visual layout. The complexity of keeping the original background context and font styles when altering, however, is an extremely difficult challenge considering the changed image must perfectly blend with the original without being altered. This article contains significant simulated data on the dynamic features of digital image editing, advertising, content development, and related fields. The system comprises key components such as 2D simulated text on the styled image (is), text image (it), masking of text (maskt), real background image (tb), real sample image (tf), text skeleton (tsk), and text styled image (tt). The source dataset contains diverse components such as background images, color variations, fonts, and text content, while the synthetic dataset consists of 49,000 randomly generated images. The dataset provides both researchers and practitioners with a rich resource for identifying and evaluating these dynamic features. The dataset is publicly accessible via the link: https://data.mendeley.com/datasets/h9kry9y46s/3.

R-loops, type I topoisomerases and cancer.

R-loops are abundant and dynamic structures ubiquitously present in human cells both in the nuclear and mitochondrial genomes. They form in cis in the wake of transcription complexes and in trans apart from transcription complexes. In this review, we focus on the relationship between R-loops and topoisomerases, and cancer genomics and therapies. We summarize the topological parameters associated with the formation and resolution of R-loops, which absorb and release high levels of genomic negative supercoiling (Sc-). We review the deleterious consequences of excessive R-loops and rationalize how human type IA (TOP3B) and type IB (TOP1) topoisomerases regulate and resolve R-loops in coordination with helicase and RNase H enzymes. We also review the drugs (topoisomerase inhibitors, splicing inhibitors, G4 stabilizing ligands) and cancer predisposing genes (BRCA1/2, transcription, and splicing genes) known to induce R-loops, and whether stabilizing R-loops and thereby inducing genomic damage can be viewed as a strategy for cancer treatment.

Identification and characterization of topoisomerase III beta poisons.

We designed and carried out a high-throughput screen for compounds that trap topoisomerase III beta (TOP3B poisons) by developing a Comparative Cellular Cytotoxicity Screen. We found a bisacridine compound NSC690634 and a thiacyanine compound NSC96932 that preferentially sensitize cell lines expressing TOP3B, indicating that they target TOP3B. These compounds trap TOP3B cleavage complex (TOP3Bcc) in cells and in vitro and predominately act on RNA, leading to high levels of RNA-TOP3Bccs. NSC690634 also leads to enhanced R-loops in a TOP3B-dependent manner. Preliminary structural activity studies show that the lengths of linkers between the two aromatic moieties in each compound are critical; altering the linker length completely abolishes the trapping of TOP3Bccs. Both of our lead compounds share a similar structural motif, which can serve as a base for further modification. They may also serve in anticancer, antiviral, and/or basic research applications.

Characterization of pumilacidin, a lipopeptide biosurfactant produced from Bacillus pumilus NITDID1 and its prospect in bioremediation of hazardous pollutants.

Highly hydrophobic compounds like petroleum and their byproducts, once released into the environment, can persist indefinitely by virtue of their ability to resist microbial degradation, ultimately paving the path to severe environmental pollution. Likewise, the accumulation of toxic heavy metals like lead, cadmium, chromium, etc., in the surroundings poses an alarming threat to various living organisms. To remediate the matter in question, the applicability of a biosurfactant produced from the mangrove bacterium Bacillus pumilus NITDID1 (Accession No. KY678446.1) is reported here. The structural characterization of the produced biosurfactant revealed it to be a lipopeptide and has been identified as pumilacidin through FTIR, NMR, and MALDI-TOF MS. The critical micelle concentration of pumilacidin was 120 mg/L, and it showed a wide range of stability in surface tension reduction experiments under various environmental conditions and exhibited a high emulsification index of as much as 90%. In a simulated setup of engine oil-contaminated sand, considerable oil recovery (39.78%) by this biosurfactant was observed, and upon being added to a microbial consortium, there was an appreciable enhancement in the degradation of the used engine oil. As far as the heavy metal removal potential of biosurfactant is concerned, as much as 100% and 82% removal was observed for lead and cadmium, respectively. Thus, in a nutshell, the pumilacidin produced from Bacillus pumilus NITDID1 holds promise for multifaceted applications in the field of environmental remediation.

2-Hydroxypropyl-ß-cyclodextrin (HPßCD) as a Potential Therapeutic Agent for Breast Cancer.

Cholesterol accumulation is documented in various malignancies including breast cancer. Consequently, depleting cholesterol in cancer cells can serve as a viable treatment strategy. We identified the potency of 2-hydroxypropyl-ß-cyclodextrin (HPßCD), a cholesterol-depletor in vitro against two breast cancer cell lines: MCF-7 (Oestrogen-receptor positive, ER+) and MDA-MB-231 (Triple negative breast cancer (TNBC)). The results were then compared against two non-cancerous cell lines using cytotoxic-, apoptosis-, and cholesterol-based assays. Treatment with HPßCD showed preferential and significant cytotoxic potential in cancer cells, inducing apoptosis in both cancer cell lines (p < 0.001). This was mediated due to significant depletion of cholesterol (p < 0.001). We further tested HPßCD in a MF-1 mice (n = 14) xenograft model and obtained 73.9%, 94% and 100% reduction in tumour size for late-, intermediate-, and early-stage TNBC, respectively. We also detected molecular-level perturbations in the expression patterns of several genes linked to breast cancer and cholesterol signalling pathways using RT2-PCR arrays and have identified SFRP1 as a direct binding partner to HPßCD through SPR drug interaction analysis. This work unravels mechanistic insights into HPßCD-induced cholesterol depletion, which leads to intrinsic apoptosis induction. Results from this study potentiate employing cholesterol depletion as a promising unconventional anticancer therapeutic strategy, which warrants future clinical investigations.

A Primed Neutrophil Subset Predicts the Risk of Bloodstream Infections in Allogeneic Hematopoietic Stem-Cell Transplant Patients: A Prospective Study.

BACKGROUND: Bloodstream infections (BSIs) are the most common infectious complication in patients who receive allogeneic hematopoietic stem-cell transplants (allo-HSCTs). Polymorphonuclear neutrophils (PMNs) are quantified to monitor the susceptibility to BSIs; however, their degree of activation is not. We previously identified a population of primed PMNs (pPMNs) with distinct markers of activation representing approximately 10% of PMNs in circulation. In this study, we investigate whether susceptibility to BSIs is related to the proportion of pPMNs rather than strictly PMN counts. METHODS: In this prospective observational study, we used flow cytometry to assess pPMNs in blood and oral rinse samples collected from patients receiving an allo-HSCT over the course of their treatment. We used the proportion of pPMNs in the blood on day 5 post-transplant to categorize patients into a high- or a low-pPMN group (>10% or <10% pPMNs). These groups were then used as a predictor of BSIs. RESULTS: A total of 76 patients were enrolled in the study with 36 in the high-pPMN group and 40 in the low-pPMN group. Patients in the low-pPMN group had lower expression of PMN activation and recruitment markers and displayed a delay in PMN repopulation of the oral cavity after the transplant. These patients were more susceptible to BSIs compared with patients in the high-pPMN group with an odds ratio of 6.5 (95% confidence interval, 2.110-25.07; P = .002). CONCLUSIONS: In patients who receive an allo-HSCT, having <10% pPMNs early in the post-transplant phase can be an independent predictor of BSI in allo-HSCT patients.

Replication-associated formation and repair of human topoisomerase IIIα cleavage complexes.

Topoisomerase IIIα (TOP3A) belongs to the conserved Type IA family of DNA topoisomerases. Here we report that human TOP3A is associated with DNA replication forks and that a "self-trapping" TOP3A mutant (TOP3A-R364W) generates cellular TOP3A DNA cleavage complexes (TOP3Accs). We show that trapped TOP3Accs that interfere with replication, induce DNA damage and genome instability. To elucidate how TOP3Accs are repaired, we explored the role of Spartan (SPRTN), the metalloprotease associated with DNA replication, which digests proteins forming DNA-protein crosslinks (DPCs). We find that SPRTN-deficient cells show elevated TOP3Accs, whereas overexpression of SPRTN lowers cellular TOP3Accs. SPRTN is deubiquitinated and epistatic with TDP2 in response to TOP3Accs. In addition, we found that MRE11 can excise TOP3Accs, and that cell cycle determines the preference for the SPRTN-TDP2 vs. the ATM-MRE11 pathways, in S vs. G2, respectively. Our study highlights the prevalence of TOP3Accs repair mechanisms to ensure normal DNA replication.

Electrically Conductive π-Intercalated Graphitic Metal-Organic Framework Containing Alternate π-Donor/Acceptor Stacks.

Two-dimensional graphitic metal-organic frameworks (GMOF) often display impressive electrical conductivity chiefly due to efficient through-bond in-plane charge transport, however, less efficient out-of-plane conduction across the stacked layers creates large disparity between two orthogonal conduction pathways and dampens their bulk conductivity. To address this issue and engineer higher bulk conductivity in 2D GMOFs, we have constructed via an elegant bottom-up method the first π-intercalated GMOF (iGMOF1) featuring built-in alternate π-donor/acceptor (π-D/A) stacks of CuII -coordinated electron-rich hexaaminotriphenylene (HATP) ligands and non-coordinatively intercalated π-acidic hexacyano-triphenylene (HCTP) molecules, which facilitated out-of-plane charge transport while the hexagonal Cu3 (HATP)2 scaffold maintained in-plane conduction. As a result, iGMOF1 attained an order of magnitude higher bulk electrical conductivity and much smaller activation energy than Cu3 (HATP)2 (σ=25 vs. 2 S m-1 , Ea =36 vs. 65 meV), demostrating that simultaneous in-plane (through-bond) and out-of-plane (through πD/A stacks) charge transport can generate higher electrical conductivity in novel iGMOFs.

PTGAC Model: A machine learning approach for constructing phylogenetic tree to compare protein sequences.

This work proposes a machine learning-based phylogenetic tree generation model based on agglomerative clustering (PTGAC) that compares protein sequences considering all known chemical properties of amino acids. The proposed model can serve as a suitable alternative to the Unweighted Pair Group Method with Arithmetic Mean (UPGMA), which is inherently time-consuming in nature. Initially, principal component analysis (PCA) is used in the proposed scheme to reduce the dimensions of 20 amino acids using seven known chemical characteristics, yielding 20 TP (Total Points) values for each amino acid. The approach of cumulative summing is then used to give a non-degenerate numeric representation of the sequences based on these 20 TP values. A special kind of three-component vector is proposed as a descriptor, which consists of a new type of non-central moment of orders one, two, and three. Subsequently, the proposed model uses Euclidean Distance measures among the descriptors to create a distance matrix. Finally, a phylogenetic tree is constructed using hierarchical agglomerative clustering based on the distance matrix. The results are compared with the UPGMA and other existing methods in terms of the quality and time of constructing the phylogenetic tree. Both qualitative and quantitative analysis are performed as key assessment criteria for analyzing the performance of the proposed model. The qualitative analysis of the phylogenetic tree is performed by considering rationalized perception, while the quantitative analysis is performed based on symmetric distance (SD). On both criteria, the results obtained by the proposed model are more satisfactory than those produced earlier on the same species by other methods. Notably, this method is found to be efficient in terms of both time and space requirements and is capable of dealing with protein sequences of varying lengths.