Advances in Computational Biology for Diagnosing Neurodegenerative Diseases: A Comprehensive Review.

The numerous and varied forms of neurodegenerative illnesses provide a considerable challenge to contemporary healthcare. The emergence of artificial intelligence has fundamentally changed the diagnostic picture by providing effective and early means of identifying these crippling illnesses. As a subset of computational intelligence, machine-learning algorithms have become very effective tools for the analysis of large datasets that include genetic, imaging, and clinical data. Moreover, multi-modal data integration, which includes information from brain imaging (MRI, PET scans), genetic profiles, and clinical evaluations, is made easier by computational intelligence. A thorough knowledge of the course of the illness is made possible by this consolidative method, which also facilitates the creation of predictive models for early medical evaluation and outcome prediction. Furthermore, there has been a great deal of promise shown by the use of artificial intelligence to neuroimaging analysis. Sophisticated image processing methods combined with machine learning algorithms make it possible to identify functional and structural anomalies in the brain, which often act as early indicators of neurodegenerative diseases. This chapter examines how computational intelligence plays a critical role in improving the diagnosis of neurodegenerative diseases such as Parkinson's, Alzheimer's, etc. To sum up, computational intelligence provides a revolutionary approach for improving the identification of neurodegenerative illnesses. In the battle against these difficult disorders, embracing and improving these computational techniques will surely pave the path for more individualized therapy and more therapies that are successful.

Leveraging a rationally designed veliparib-based anilide eliciting anti-leukemic effects for the design of pH-responsive polymer nanoformulation.

Careful recruitment of the components of the HDAC inhibitory template culminated in veliparib-based anilide 8 that elicited remarkable cell growth inhibitory effects against HL-60 cell lines mediated via dual modulation of PARP [(IC50 (PARP1) = 0.02 nM) and IC50 (PARP2) = 1 nM)] and HDACs (IC50 value = 0.05, 0.147 and 0.393 µM (HDAC1, 2 and 3). Compound 8 downregulated the expression levels of signatory biomarkers of PARP and HDAC inhibition. Also, compound 8 arrested the cell cycle at the G0/G1 phase and induced autophagy. Polymer nanoformulation (mPEG-PCl copolymeric micelles loaded with compound 8) was prepared by the nanoprecipitation technique. The mPEG-PCL diblock copolymer was prepared by ring-opening polymerization method using stannous octoate as a catalyst. The morphology of the compound 8@mPEG-PCL was examined using TEM and the substance was determined to be monodispersed, spherical in form, and had an average diameter of 138 nm. The polymer nanoformulation manifested pH-sensitive behaviour as a greater release of compound 8 was observed at 6.2 pH as compared to 7.4 pH mimicking physiological settings. The aforementioned findings indicate that the acidic pH of the tumour microenvironment might stimulate the nanomedicine release which in turn can attenuate the off-target effects precedentially claimed to be associated with HDAC inhibitors.

Major sources of sinking particulate organic matter in the western Bay of Bengal.

Impacts of river discharge on coastal ocean processes are multi-dimensional. Studies on sinking particle fluxes, composition and their seasonal variability in coastal oceans are very limited. In this study, we investigated the impact of river discharge on seasonal variability in sinking fluxes of total mass, biogenic and lithogenic material in a river-dominated continental margin, western coastal Bay of Bengal. Higher POC, lithogenic and total mass fluxes were found during early southwest monsoon, and are decoupled with peak river discharge and elevated primary production. It is attributed to cross-shelf transport of re-suspended surface sediments from shelf region. Peak river discharge followed by elevated chlorophyll-a suggest nutrients supply though river discharge support primary production. Elemental C:N ratios, δ13C and δ15N results likely suggest that both marine and terrestrial sources contributed to sinking POM, . Overall, higher sinking fluxes during southwest monsoon than rest of the year suggest that seasonal river discharge exerts considerable impact on sinking fluxes in the western coastal Bay of Bengal.

In silico investigation of potential phytoconstituents against ligand- and voltage-gated ion channels as antiepileptic agents.

The most promising anticonvulsant phytocompounds were explored in this work using docking, molecular dynamic (MD) simulation, and Molecular Mechanics-Poisson-Boltzmann Surface Area (MM-PBSA) approaches. A total of 70 phytochemicals were screened against α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA), N-methyl-d-aspartate (NMDA), voltage-gated sodium ion channels (VGSC), and carbonic anhydrase enzyme II (CA II) receptors, and the docking results were compared to the reference drug phenytoin. Amentoflavone displayed the highest affinity for AMPA and VGSC receptors, with docking scores of - 10.4 and - 10.1 kcal/mol, respectively. Oliganthin H-NMDA and epigallocatechin-3-gallate-CA II complexes showed docking scores of - 10.9 and - 6.9 kcal/mol, respectively. All four complexes depicted a high dock score compared to the phenytoin complex at the binding site of the corresponding proteins. The MD simulation investigated the stabilities and favorable conformation of apoproteins and ligand/reference-bound complexes. The results revealed that proteins AMPA, VGSC, and CA II were more efficiently stabilized by lead phytochemicals than phenytoin binding. Additionally, principal component analysis and MM-PBSA results suggested that these lead phytocompounds have good compactness and strong binding free energy. Further, physicochemical and pharmacokinetic studies revealed that these final lead phytochemicals would be suitable for oral intake, have sufficient intestinal permeability, and have the ability to cross the blood-brain barrier (BBB). Comprehensively, this study predicted amentoflavone as the best lead phytochemical out of the 70 anticonvulsant phytocompounds that can be used to treat epilepsy. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03948-1.

Tiny stresses are capable of triggering earthquakes and tremors in Arunachal Himalaya.

The Arunachal Himalaya has been hosting some notable events in the recent past. The tectonic history of Arunachal Himalaya is complex and has been influenced by several major tectonic events, including the 1950 Mw8.6 Assam-Tibet earthquake. In this study, we explored the effect of dynamic stresses generated by teleseismic events on the triggering of seismicity in the region. We analyzed 34 large teleseismic events since 2010 and found triggering during six events. The change in seismicity was also confirmed by analysis with the STA/LTA method. The triggering in the region occurred in the form of earthquakes and tremors. The dynamic stress as low as 1 kPa was found capable of triggering. The back-azimuth angle does not play an important role in the triggering. The angle direction of incoming waves with respect to the fault ~ 60° and ~ 120° is the possible reason for triggering in the region. The triggering occurred in the Mishmi and Main Central Thrust regions. The largest triggered event, ML2.3, was triggered 7.5 h after the 2012 Indian Ocean earthquake of Mw8.6. The region is tectonically very sensitive and tiny stresses are capable of triggering seismicity in Arunachal Pradesh.

Ossifying Fibroma: A Case Report of an Unusual Presentation of Angiodysplastic Disease with Review of Literature.

Ossifying fibroma is a nonneoplastic developmental disease of osseous tissue seen rarely in association with Sturge-Weber syndrome. It is a lesion of unknown aetiology, uncertain pathogenesis, and diverse histopathology. The aim of this study is to report an unusual case of in a 11-year-old male of SWS. The rarity of the case and the fact that ossifying fibroma may be associated with Sturge-Weber syndrome propelled us to report it. Physical examination showed facial asymmetry (due to hemifacial swelling) without any tenderness, fluctuation, ocular pain, or ophthalmoplegia. Imaging studies revealed a solid mass involving the left maxilla and orbital floor. A conservative therapeutic approach to these lesions may be sufficient to relieve signs and symptoms effectively. Periodic follow-up is indicated to detect recurrences or malignant changes in the early stages.

Water-soluble PEG segmented mannose-based macromolecules: Synthesis, characterization and their biocompatibility.

The macromolecular architectures, namely mannose-based methacrylate acetyl-mannopyranoside and PEG block copolymers [AB type copolymer [PEG-b-PMAM], poly(ethyleneglycol)-b-poly(methacryl-2,3,4,6-tetra-O-acetyl-D-mannopyranoside) and ABA type copolymer [PMAM-b-PEG-b-PMAM], poly(methacryl-2,3,4,6-tetra-O-acetyl-D-mannopyranoside)-b-poly(ethyleneglycol)-b-poly(methacryl-2,3,4,6-tetra-O-acetyl-D-mannopyranoside)] were synthesized by atom transfer radical polymerization (ATRP) method that were deacetylated to generate the corresponding water-soluble and biocompatible glycopolymer macromolecules. The molecular weight of acetyl and deacetylate macromolecules was in the range of 7083-9499 and 4659-6026, as determined by GPC and proton NMR spectra. The 5 % decomposition temperatures for acetylated methacrylate macromolecules (218-299 °C) were higher than the corresponding water-soluble macromolecules (204-248 °C). The conjugation of poly(methacryl-2,3,4,6-tetra-O-acetyl-D-mannopyranoside) (PMAM) segment with the PEG block decreased the glass transition (Tg) value, and the water-soluble macromolecules displayed Tg in the range of 92-95 °C. The biocompatibility of the synthesized water-soluble mannose-based macromolecules was determined using Human Bone Derived Cells (HBDC) culture with the TCP (Tissue culture plastic) template as control. Using three different concentrations of the synthesized glycopolymers, HBDC's were cultured for 1, 3, and 7 days. The effect of mannomethacrylate macromolecules on mitochondrial activity of HBDC's was estimated using colorimetry that showed the conversion of MTS [3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium-bromide] to formazan (MTS assay). ABA type diblock copolymer architecture exhibited increased absorbance values of 3 and 7 day cultures at 1-100 M concentrations, with the highest values observed at a concentration of 1 M for day 3 cultures. The design of these novel mannose-based macromolecules is important for improving cell proliferation, cell adhesion, and osteointegration efficiency.

Relating algal-derived extracellular and intracellular dissolved organic nitrogen with nitrogenous disinfection by-product formation.

The dissolved organic nitrogen (DON) pool from algal-derived extracellular and intracellular organic matter (EOM and IOM) comprises proteins, peptides, free amino acids and carbohydrates, of which, proteins can contribute up to 100% of the DON. Previous reports of algal-derived DON character have focused on bulk properties including concentration, molecular weight and hydrophobicity. However, these can be similar between algal species and between the EOM and IOM even when the inherent molecular structures vary. A focus on bulk character presents challenges to the research on algal-derived nitrogenous-disinfection by-product (N-DBP) formation as N-DBP formation is sensitive to the changes in molecular structure. Hence, the main aim of this study was to characterize algal EOM and IOM-derived DON, specifically proteinaceous-DON, using a combination of bulk and molecular characterization techniques to enable a more detailed exploration of the relationship between the character of algal-derived proteins and the N-DBP formation potential. DON from the EOM and IOM of four commonly found algae and cyanobacteria in natural waters were evaluated, namely Chlorella vulgaris, Microcystis aeruginosa, Dolichospermum circinale, and Cylindrospermopsis raciborskii. It was observed that 77-96% of total DON in all EOM and IOM samples was of proteinaceous origin. In the proteins, DON concentrations were highest in the high molecular weight fraction of IOM-derived bulk proteins (0.13-0.75 mg N L-1) and low to medium molecular weight fraction of EOM-derived bulk proteins (0.15-0.63 mg N L-1) in all species. Similar observations were also made via sodium dodecyl sulphate polyacrylamide gel electrophoresis and liquid chromatography-high resolution mass spectrometry. Solid-state 15N nuclear magnetic resonance (NMR) spectroscopy of the EOM and IOM revealed the existence of common aliphatic and heterocyclic N-groups in all samples, including a dominant 2° amide peak. Species dependent variability was also observed in the spectra, particularly in the EOM; e.g. nitro signals were found only in the Cylindrospermopsis raciborskii EOM. Dichloroacetonitrile (DCAN) and N-nitrosamine concentrations from the EOM of the species evaluated in this study were lower than the guideline limits set by regulatory agencies. It is proposed that the dominant 2° amide in all samples decreased N-DBP formation upon chlorination. For chloramination, the presence of nitro groups and aliphatic and heterocyclic N-DBP precursors could cause variable N-nitrosamine formation. Compared to non-algal impacted waters, algae-laden waters are characterised by low organic carbon: organic nitrogen ratios of ∼7-14 and elevated DON and protein concentrations. Hence, relying only on bulk characterization increases the perceived risk of N-DBP formation from algae-laden waters.

Microalgae harvesting using flocculation and dissolved air flotation: Selecting the right vessel for lab-scale experiments.

Flocculation combined with dissolved air flotation (DAF) is a promising technology for harvesting microalgae; therefore, optimisation of flocculant-DAF operating conditions are frequently explored in laboratory experiments. DAF systems have jars of differing volumes, height to diameter ratios, shapes and materials used to manufacture the jars; thus, the harvesting efficiency (η) may differ between these jars. The aim was to systematically compare η between different types of benchtop DAF jars. Evaluation of 30 different types of DAF jars revealed that η was not influenced by the volume of the jars, but was impacted by the height to diameter ratio, with optimal η at a ratio ranging between 1.6 and 2.05. There was no difference in η between cylindrical and cuboid jars, but jars made of hydrophobic (polypropylene) plastic resulted in a lower η. Overall, these results are useful to guide the design of lab-scale DAF microalgae harvesting experiments.

Enzyme-substrate interactions in orotate-mimetic OPRT inhibitor complexes: a QM/MM analysis.

Orotate phosphoribosyltransferase (OPRT) catalyses the reversible phosphoribosyl transfer from α-D-5-phosphoribosyl-1-pyrophosphate (PRPP) to orotic acid (OA) to yield orotidine 5'-monophosphate (OMP) during the de novo synthesis of nucleotides. Numerous studies have reported the inhibition of this reaction as a strategy to check diseases like tuberculosis, malaria and cancer. Insight into the inhibition of this reaction is, therefore, of urgent interest. In this study, we implemented a QM/MM framework on OPRT derived from Saccharomyces cerevisiae to obtain insights into the competitive binding of OA and OA-mimetic inhibitors by quantifying their interactions with OPRT. 4-Hydroxy-6-methylpyridin-2(1H) one showed the best inhibiting activity among the structurally similar OA-mimetic inhibitors, as quantified from the binding energetics. Our analysis of protein-ligand interactions unveiled the association of this inhibitory ligand with a strong network of hydrogen bonds, a large contribution of hydrophobic contacts, and bridging water molecules in the binding site. The ortho-substituted CH3 group in the compound resulted in a large population of π-electrons in the aromatic ring of this inhibitor, supporting the ligand binding further.

Variations of generalized weak contractions in partially ordered b-metric space.

OBJECTIVES: This paper explored the fixed point results for the mappings satisfying generalized weak contractive conditions in a complete partially ordered b-metric space. These contractions are some variations of the work done by the authors (Mituku et al. in BMC Res Notes 13:537. https://doi.org/10.1186/s13104-020-05354-1 , 2020; Seshagiri et al. in BMC Res Notes 13:451. https://doi.org/10.1186/s13104-020-05273-1 , 2020, BMC Res Notes 14:390. https://doi.org/10.1186/s13104-021-05801-7 , 2021, BMC Res Notes 14:263. https://doi.org/10.1186/s13104-021-05649-x , 2021) in the same context. To validate the results a few examples are provided. RESULT: The aim of this work is to prove some fixed point results of the self mappings in ordered b-metric space satisfying variant generalized weak contraction conditions. These results generalize some known results in the provided literature.

Coupled fixed points of ( ϕ ˆ , ψ ˆ , θ ˆ ) -contractive mappings in partially ordered b-metric spaces.

We aim to prove the existence and uniqueness of the fixed points for the self mappings satisfying generalized contractions involving altering distance functions in ordered metric type space. The results obtained in this work are generalizing some important findings in the literature and few illustrations are given to support the outcomes.

A bi-directional deep learning architecture for lung nodule semantic segmentation.

Lung nodules are abnormal growths and lesions may exist. Both lungs may have nodules. Most lung nodules are harmless (not cancerous/malignant). Pulmonary nodules are rare in lung cancer. X-rays and CT scans identify the lung nodules. Doctors may term the growth a lung spot, coin lesion, or shadow. It is necessary to obtain properly computed tomography (CT) scans of the lungs to get an accurate diagnosis and a good estimate of the severity of lung cancer. This study aims to design and evaluate a deep learning (DL) algorithm for identifying pulmonary nodules (PNs) using the LUNA-16 dataset and examine the prevalence of PNs using DB-Net. The paper states that a new, resource-efficient deep learning architecture is called for, and it has been given the name of DB-NET. When a physician orders a CT scan, they need to employ an accurate and efficient lung nodule segmentation method because they need to detect lung cancer at an early stage. However, segmentation of lung nodules is a difficult task because of the nodules' characteristics on the CT image as well as the nodules' concealed shape, visual quality, and context. The DB-NET model architecture is presented as a resource-efficient deep learning solution for handling the challenge at hand in this paper. Furthermore, it incorporates the Mish nonlinearity function and the mask class weights to improve segmentation effectiveness. In addition to the LUNA-16 dataset, which contained 1200 lung nodules collected during the LUNA-16 test, the LUNA-16 dataset was extensively used to train and assess the proposed model. The DB-NET architecture surpasses the existing U-NET model by a dice coefficient index of 88.89%, and it also achieves a similar level of accuracy to that of human experts.

Mechanistic elucidations of sesquiterpenes ameliorating viral infections: A review.

Sesquiterpenes are important in human health because they can treat viral infection, cardiovascular disease, and cancer. Sesquiterpenes have also been shown to increase the sensitivity of tumor cells to conventional pharmacological therapies, in addition to their antiviral effects. The present review article was drafted with an intention to gather information regarding sesquiterpenes and its medicinal importance. The role of sesquiterpenes in the endogenous production of sesquiterpenes by plants and fungi, as well as the mechanisms by which they are effective against viral infection, are discussed in this review. Different online libraries such as PUBMED, Sciencedirect, MEDLINE were assessed to gather information, additionally, books, magzagines, journals, and scientific newspapaers were also studied to make this article more informative. This review examines novel synthesis mechanisms, their cyclization, purification techniques, and the diverse ecological roles sesquiterpenes play in the plant producer, which varies according to the plant and the chemical under consideration. In this article, we have discussed the consequences of sesquiterpenes and their properties for future crop productivity. We have addressed the many forms of sesquiterpenes that have been shown to have antiviral activity in various diseases. The consequences of sesquiterpenes and their properties are very useful for future crop productivity. We have addressed the many forms of sesquiterpenes that have been shown to have antiviral activity in the treatment of various diseases. PRACTICAL APPLICATIONS: Novel synthesis mechanisms, their cyclization, purification techniques, and the diverse ecological roles of sesquiterpenes will be very helfpul in drug development process. Sesquiterpene lactones are shown in this review to have qualities that warrant further scientific investigation in order to stimulate preclinical and clinical trials leading to the creation of novel medications. For antiviral drug development, the sesquiterpenes are a good prospective lead molecule because they can suppress viral replication by disrupting vRNA production and viral protein production.

Understanding the factors contributing to groundwater salinity in the coastal region of Andhra Pradesh, India.

The present study focused on understanding the factors responsible for groundwater salinity in the coastal region, Prakasam district, Andhra Pradesh, India. Groundwater samples were collected and analysed for pH, EC, TDS, TA, TH, CH, NCH, EA, Ca2+, Mg2+, Na+, K+, HCO3-, Cl-, SO42-, NO3-, and F-. Groundwater quality was assessed using entropy weighted water quality index (EWQI), Chadha and Gibbs diagrams, ionic ratios, chloro-alkaline indices (CA), saturation indices (SI), principal component analysis (PCA), and hierarchical cluster analysis (HCA). TDS vs TH indicated that 86% of groundwater samples fall under brackish-cum-very hard water-quality type, while TA and TH relationship showed that 70% and 30% of groundwater samples fall under non­carbonate hardness (NCH) and excess alkalinity (EA), respectively. EWQI classified groundwater samples into medium (22%), poor (40%), and exremely poor (38%) water quality types, indicating that most samples are not suitable for drinking purposes. Hydrogeochemical types in Chadha diagram showed saline water (Na+-Cl-) type in 92% of groundwater samples. Ionic ratios indicated that anthropogenic activities resulting from the leaching of surface water pollutants are the main source of groundwater pollution. Base ion exchange was indicated as the main process in CA indices. SI revealed precipitation of the calcite phase and dissolution of the gypsum and halite phases in groundwater. Evaporation appeared in Gibb's diagram as a primary process rather than a geogenic origin. PC1 (Na+, Cl-, SO42-, Mg2+, K+, and NO3-) and PC2 (HCO3- and F-) were considered salinity-process and alkalinity-process, respectively. The main sources of salinity in groundwater are brackish-water aquaculture and salt-making activities with household waste, septic tank spills, irrigation-return-flows, and chemical fertilizers being secondary sources. HCA classified groundwater samples into Group-I (46%), which represents domestic water, agricultural activities, etc., Group-II (30.24%), which shows the influence of both Group-I and Group-II, and Group-III (23.76%), which specifies brackish-water aquaculture and salt-making activities. Consequently, the present study obviously indicated that the groundwater quality of anthropogenic origin has largely overcome the influence of geogenic sources. The EWQI classification spatially delineated the study region into medium, high, and very high vulnerable zones, covering 28.69%, 32.75%, and 38.56%, respectively. Therefore, it is suggested to control the dumping of domestic waste and septic tank leaks, limit irrigation-return-flows and chemical fertilizers, ban brackish water aquaculture and salt production activities, and strictly implement an aquifer recharge management strategy to ensure human health. This study will assist decision-makers in addressing groundwater salinity issues in coastal regions.

Accommodation of ring C expanded deoxyvasicinone in the HDAC inhibitory pharmacophore culminates into a tractable anti-lung cancer agent and pH-responsive nanocarrier.

A fragment recruitment process was conducted to pinpoint a suitable fragment for installation in the HDAC inhibitory template to furnish agents endowed with the potential to treat lung cancer. Resultantly, Ring C expanded deoxyvasicinone was selected as an appropriate surface recognition part that was accommodated in the HDAC three-component model. Delightfully, fused quinazolinone 6 demonstrating a magnificent anticancer profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80-0.96 µM) was identified. Results of the mechanistic studies confirmed that the cell growth inhibitory effects of compound 6 stems for HDAC6 (IC50 = 12.9 nM), HDAC1 (IC50 = 49.9 nM) and HDAC3 inhibition (IC50 = 68.5 nM), respectively. Compound 6 also suppressed the colony formation ability of A549 cells, induced apoptosis, and increased autophagic flux. Key interactions of HDAC inhibitor 6 within the active site of HDAC isoforms were figured out through molecular modeling studies. Furthermore, a pH-responsive nanocarrier (Hyaluronic acid - fused quinazolinone 6 nanoparticles) was designed and assessed using a dialysis bag approach under both normal and acidic circumstances that confirmed the pH-sensitive nature of NPs. Delightfully, the nanoparticles demonstrated selective cell viability reduction potential towards the lung cancer cell lines (A549 lung cancer cell lines) and were found to be largely devoid of cell growth inhibitory effects under normal settings (L929, mouse fibroblast cells).

Niraparib Shows Superior Tissue Distribution and Efficacy in a Prostate Cancer Bone Metastasis Model Compared with Other PARP Inhibitors.

Patients with prostate cancer whose tumors bear deleterious mutations in DNA-repair pathways often respond to PARP inhibitors. Studies were conducted to compare the activity of several PARP inhibitors in vitro and their tissue exposure and in vivo efficacy in mice bearing PC-3M-luc-C6 prostate tumors grown subcutaneously or in bone. Niraparib, olaparib, rucaparib, and talazoparib were compared in proliferation assays, using several prostate tumor cell lines and in a cell-free PARP-trapping assay. PC-3M-luc-C6 cells were approximately 12- to 20-fold more sensitive to PARP inhibition than other prostate tumor lines, suggesting that these cells bear a DNA damage repair defect. The tissue exposure and efficacy of these PARP inhibitors were evaluated in vivo in PC-3M-luc-C6 subcutaneous and bone metastasis tumor models. A steady-state pharmacokinetic study in PC-3M-luc-C6 tumor-bearing mice showed that all of the PARP inhibitors had favorable subcutaneous tumor exposure, but niraparib was differentiated by superior bone marrow exposure compared with the other drugs. In a PC-3M-luc-C6 subcutaneous tumor efficacy study, niraparib, olaparib, and talazoparib inhibited tumor growth and increased survival to a similar degree. In contrast, in the PC-3M-luc-C6 bone metastasis model, niraparib showed the most potent inhibition of bone tumor growth compared with the other therapies (67% vs. 40%-45% on day 17), and the best survival improvement over vehicle control [hazard ratio (HR), 0.28 vs. HR, 0.46-0.59] and over other therapies (HR, 1.68-2.16). These results show that niraparib has superior bone marrow exposure and greater inhibition of tumor growth in bone, compared with olaparib, rucaparib, and talazoparib.

Estimation of groundwater pollution levels and specific ionic sources in the groundwater, using a comprehensive approach of geochemical ratios, pollution index of groundwater, unmix model and land use/land cover - A case study.

This study aimed to evaluate the degree of groundwater pollution and to assess the contribution of specific ionic sources to groundwater, thereby helping to identify the changes in groundwater chemistry and also in groundwater quality from a rural part of Telangana, India, using the comprehensive understanding of geochemical ratios (GR), pollution index of groundwater (PIG), unmix model (UM), and land use/land cover. Groundwater samples collected (22) from the study area were analysed for pH, EC, TDS, Ca2+, Mg2+, Na+, K+, HCO3-, Cl-, SO42-, NO3-, and F-. The hydrogeochemical diagram showed the dominant groundwater type of Ca2+- Mg2+- HCO3- due to the water-soil-rock interactions. GR, chloro-alkaline indices, and saturation indices revealed the groundwater chemistry that explains the mineral weathering and dissolution, ion exchange, and evaporation processes as the chief geogenic origin, and also the contamination of surface water due to the influence of household wastewater, septic tank leaks, irrigation-return-flows, chemical composts, etc. as the secondary anthropogenic sources on the aquifer system. Changes in groundwater quality from the recharge area to the discharge area and the correlation coefficient of chemical variables further supported the sources of geogenic and anthropogenic origins. According to PIG's calculations, the present study area was classified as the insignificant pollution zone (5.89%), which shows all chemical variables within their drinking water quality limits, and the low pollution zone (43.34%), medium pollution zone (27.48%), high pollution zone (17.34%), and very high pollution zone (5.95%), which exhibit the TDS, Mg2+, Na+, K+, HCO3-, Cl-, NO3-, SO42-, and F-contents above the drinking water quality standards. This indicates the gradual increase in the intensity of pollution activity. UM also classified the contribution of specific ions (>50%) into three sources: Source I (K+) measures the poor sewage conditions and potash fertilizers; Source II (SO42-, Mg2+, NO3-, Na+, and Ca2+) specifies the poor sewage conditions, irrigation-return-flows, and chemical fertilizers (gypsum and nitrate); and Source III (F- and HCO3-) represents the dissolution of fluoride minerals as a major contributor to groundwater chemistry. Furthermore, the land use/land cover observations had also supported the assessment of groundwater pollution levels and the contribution of specific ionic sources made by PIG and UM. As a result, the present study clearly indicated that groundwater quality of a geogenic origin is primarily overcome the impact of anthropogenic sources. Therefore, the present study suggested strategic measures to control groundwater pollution and improve groundwater quality.

Judging the sources of inferior groundwater quality and health risk problems through intake of groundwater nitrate and fluoride from a rural part of Telangana, India.

Evaluation of groundwater quality and related health hazards is a prerequisite for taking preventive measures. The rural region of Telangana, India, has been selected for the present study to assess the sources and origins of inferior groundwater quality and to understand the human health risk zones for adults and children due to the consumption of nitrate ([Formula: see text])- and fluoride (F-)-contaminated groundwater for drinking purposes. Groundwater samples collected from the study region were determined for various chemical parameters. Groundwater quality was dominated by Na+ and [Formula: see text] ions. Piper's diagram and bivariate plots indicated the carbonate water type and silicate weathering as a main factor and man-made contamination as a secondary factor controlling groundwater chemistry; hence, the groundwater quality in the study region is low. According to the Groundwater Quality Index (GQI) classification, 48.3% and 51.7% of the total study region are excellent (GQI: < 50) and good (GQI: 50 to 100) water quality types, respectively, for drinking purposes. However, [Formula: see text] ranged from 0.04 to 585 mg/L, exceeding the drinking water quality limit of 45 mg/L in 34% of the groundwater samples due to the effects of nitrogen fertilizers. This was supported by the relationship of [Formula: see text] with TDS, Na+, and Cl-. The F- content was from 0.22 to 5.41 mg/L, which exceeds the standard drinking water quality limit of 1.5 mg/L in 25% of the groundwater samples. The relationship of F- with pH, Ca2+, Na+, and [Formula: see text] supports the weathering and dissolution of fluoride-rich minerals for high F- content in groundwater. They were further supported by a principal component analysis. The Health Risk Index (HRI) values ranged from 0.20 to 20.10 and 0.36 to 30.90 with a mean of 2.82 and 4.34 for adults and children, respectively. The mean intensity of HRI (> 1.0) was 1.37 times higher in children (5.70) than in adults (4.16) due to the differences in weight size and exposure time. With an acceptable limit of more than 1.0, the study divided the region into Northern Safe Health Zone (33.3% for adults and 28.1% for children) and Southern Unsafe Health Zone (66.7% for adults and 71.9% for children) based on the intensity of agricultural activity. Therefore, effective strategic measures such as safe drinking water, denitrification, defluoridation, rainwater harvesting techniques, sanitary facilities, and chemical fertilizer restrictions are recommended to improve human health and protect groundwater resources.

Fixed point results of weakly contraction mappings in partially ordered b-metric spaces.

OBJECTIVES: We explored the results of fixed point, coincidence point and coupled coincidence point for the mappings in an ordered metric spaces. Our results generalized and extended the well-known results in the literature. Some numerical examples are provided for justifying the results obtained. RESULT: Some fixed point results are found for a self mapping in a partially ordered b-metric space which satisfies a generalized week contraction condition. Furthermore, these results are extended for two self mappings for obtaining coincidence point, coupled coincidence point and coupled common fixed point in the same context. A few examples are presented to support the findings.