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Background: The current investigation entails the characterization of seven degradation products (DPs) formed in different stress conditions of gilteritinib employing liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methodology: This study developed a stability-indicating reversed-phase high-performance liquid chromatographic (HPLC) method for precisely determining gilteritinib in the presence of its process-related impurities in bulk drug and formulation samples. To explore the stability profile of gilteritinib, it was exposed to forced degradation experiments conducted under various conditions, including acidic, basic, oxidative, photolytic, and thermal stress. These experiments revealed the degradation of gilteritinib under basic, acidic, and photolytic conditions, forming seven distinct DPs. Result: The chromatographic resolution of gilteritinib and its impurities along with DPs was effectively achieved using a Waters Symmetry C18 (250 mm × 4.6 mm, 5 μm) column using equal volumes of solvent A and B (pH 4.5 phosphate buffer and acetonitrile in 25:75 (v/v) as solvent A, acetonitrile and methanol in 75: 25 (v/v) as solvent B) pumped isocratically at 0.7 mL/min and 230 nm wavelength. The method produces an accurate fit calibration curve in 25-175 μg/mL for gilteritinib and LOQ (0.025 μg/mL) – 0.175 μg/mL for its impurities with acceptable precision, accuracy, and recovery. Conclusion: The efficacy of this method was validated through LC-MS/MS, which allowed for the verification of the chemical structures of newly generated degradation products of gilteritinib. Hence, this method is appropriate for the resolution and evaluation of process-related impurities of gilteritinib and can also be applied for evaluating stress degradation products.

With rising infection rates in recent years, Vibrio vulnificus poses an increasing threat to public safety in the coastal brackish Baltic Sea. It is therefore important to monitor this organism and assess the V. vulnificus infection risk on a more regular basis. However, as the coastline of the Baltic Sea is 8000 km long and shared by nine nations, a convenient, fast, inexpensive, yet efficient V. vulnificus identification method is essential. We evaluated the effectiveness of a two-step agar-based approach consisting of successive Vibrio isolation and cultivation on thiosulphate-citrate-bile salt sucrose (TCBS) agar and CHROMagar™ Vibrio for V. vulnificus in comparison with V. cholerae, V. parahaemolyticus, and V. alginolyticus. Our study contains isolates from water and sediment across a broad expanse of the Baltic Sea including 13 locations and two different summers, the time of year during which Vibrio infections are usually much more frequent. Confirmation of isolate species identity was carried out using molecular analyses. The two-step agar plating method performed well across different locations and timeframes in correctly identifying V. vulnificus by more than 80%, but the sensitivity in other Vibrio species varied. Thus, our approach yielded promising results as a potential tool for early V. vulnificus detection across a broad timeframe and transect of the Baltic Sea and potentially other brackish environments.

Distributed denial of service (DDoS) attack is one of the most hazardous assaults in cloud computing or networking. By depleting resources, this attack renders the services unavailable to end users and leads to significant financial and reputational damage. Hence, identifying such threats is crucial to minimize revenue loss, market share, and productivity loss and enhance the brand reputation. In this study, we implemented an effective intrusion detection system using deep learning approach. The suggested framework includes three phases: Data pre-processing, Data balancing, and Classification. First, we prepare the valid data, which is helpful for further processing. Then, we balance the given pre-processed data by Conditional generative adversarial network (CGAN), and as a result, we can minimize the bias towards the majority classes. Finally, we distinguish whether the traffic is attack or benign using a stacked sparse denoising autoencoder (SSDAE) with a firefly-black widow (FA-BW) hybrid optimization algorithm. All these experiments are validated through the CICDDoS2019 dataset and compared with well-received techniques. From these findings, we observed that the proposed strategy detects DDoS attacks significantly more accurately than other approaches. Based on our findings, this study highlights the crucial role played by advanced deep learning techniques and hybrid optimization algorithms in strengthening cybersecurity against DDoS attacks., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Cancer cohorts are now known to be associated with increased rates of clonal hematopoiesis (CH). We sort to characterize the hematopoietic compartment of patients with melanoma and non-small cell lung cancer (NSCLC) given our recent population level analysis reporting evolving rates of secondary leukemias. The advent of immune checkpoint blockade (ICB) has dramatically changed our understanding of cancer biology and has altered the standards of care for patients. However, the impact of ICB on hematopoietic myeloid clonal expansion remains to be determined. We studied if exposure to ICB therapy affects hematopoietic clonal architecture and if their evolution contributed to altered hematopoiesis. Blood samples from patients with melanoma and NSCLC ( n = 142) demonstrated a high prevalence of CH. Serial samples (or post ICB exposure samples; n = 25) were evaluated in melanoma and NSCLC patients. Error-corrected sequencing of a targeted panel of genes recurrently mutated in CH was performed on peripheral blood genomic DNA. In serial sample analysis, we observed that mutations in DNMT3A and TET2 increased in size with longer ICB exposures in the melanoma cohort. We also noted that patients with larger size DNMT3A mutations with further post ICB clone size expansion had longer durations of ICB exposure. All serial samples in this cohort showed a statistically significant change in VAF from baseline. In the serial sample analysis of NSCLC patients, we observed similar epigenetic expansion, although not statistically significant. Our study generates a hypothesis for two important questions: (a) Can DNMT3A or TET2 CH serve as predictors of a response to ICB therapy and serve as a novel biomarker of response to ICB therapy? (b) As ICB-exposed patients continue to live longer, the myeloid clonal expansion may portend an increased risk for subsequent myeloid malignancy development. Until now, the selective pressure of ICB/T-cell activating therapies on hematopoietic stem cells were less known and we report preliminary evidence of clonal expansion in epigenetic modifier genes (also referred to as inflammatory CH genes).

Crop losses to pests were the main obstacle to food security globally. Pest control was a laudable exercise, but the exercise could be hindered by the inevitable adjustment between pest reductions, operation costs as well as impacts on the environment and human health. The pest could be controlled by many methods, but biological control was the most popular technique because it addressed inevitable trade-offs between costs and side effects. In this paper, a mathematical model was developed to quantify intricate biological procedures in the context of biological control using prey-predator mechanisms. Three equilibrium points (one trivial and two non-trivial) were derived, and the stability of each equilibrium point was examined. The stability results indicated that the adoption of biological control might neutralize pest infestation but the situation might not persist (unstable trivial equilibrium). It was also discovered that pest control through biological means might fail if the predator was wrongly selected or if the population of the predator vanished while the pest remained in existence (unstable non-trivial equilibrium). The analytical results were finally justified by a means of simulation via a computer-in-built maple program., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The cubic perovskite SrMoO 3 with a paramagnetic ground state and remarkably low room-temperature resistivity has been considered as a suitable candidate for the new-era oxide-based technology. However, the difficulty of preparing single-phase SrMoO 3 thin films by hydrogen-free sputtering has hindered their practical use, especially due to the formation of thermodynamically favorable SrMoO 4 impurity. In this work, we developed a radio frequency sputtering technology enabling the reduction reaction and achieved conductive epitaxial SrMoO 3 films with pure phase from a SrMoO 4 target in a hydrogen-free, pure argon environment. We demonstrated the significance of controlling the target-to-substrate distance (TSD) on the synthesis of SrMoO 3 ; the film resistivity drastically changes from 1.46 × 10 5 μΩ·cm to 250 μΩ·cm by adjusting the TSD. Cross-sectional microstructural analyses demonstrated that films with the lowest resistivity, deposited for TSD = 2.5 cm, possess a single-phase SrMoO 3 with an epitaxial perovskite structure. The formation mechanism of the conductive single-phase SrMoO 3 films can be attributed to the plasma-assisted growth process by tuning the TSD. Temperature-dependent resistivity and Hall effect studies revealed metal-like conducting properties for low-resistive SrMoO 3 films, while the high-resistive ones displayed semiconductor-like behavior. Our approach makes hydrogen-free, reliable and cost-efficient scalable deposition of SrMoO 3 films possible, which may open up promising prospects for a wide range of future applications of oxide materials., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by National Institute for Materials Science in partnership with Taylor & Francis Group.)

Local magnetostructural changes and dynamical spin fluctuations in doubly diluted spinel Ti x Mn 1‒ x (Fe y Co 1‒ y ) 2 O 4 has been reported by means of neutron diffraction and magnetization studies. Two distinct sets of compositions (i) x (Ti) = 0.20 and y (Fe) = 0.18; (ii) x (Ti) = 0.40 and y (Fe) = 0.435 have been considered for this study. The first compound of equivalent stoichiometry Ti 0.20 Mn 0.80 Fe 0.36 Co 1.64 O 4 exhibits enhanced tetragonal distortion across the ferrimagnetic transition temperature T C = 258 K in comparison to the end compound MnCo 2 O 4 ( T C ∼ 180 K) with a characteristic ratio c t /√2 a t of 0.99795(8) demonstrating robust lattice-spin-orbital coupling. However, in the second case Ti 0.40 Mn 0.60 Fe 0.87 Co 1.13 O 4 with higher B -site compositions, the presence of Jahn-Teller ions with distinct behavior appears to counterbalance the strong tetragonal distortion thereby ceasing the lattice-spin-orbital coupling. Both the investigated systems show the coexistence of noncollinear antiferromagnetic and ferrimagnetic components in cubic and tetragonal settings. On the other hand, the dynamical ac-susceptibility, χ ac ( T ) reveals a cluster spin-glass state with Gabay-Toulouse (GT) like mixed phases behaviour below T C . Such dispersive behaviour appears to be sensitive to the level of octahedral substitution. Further, the field dependence of χ ac ( T ) follows the weak anisotropic GT-line behaviour with crossover exponent Φ lies in the range 1.38-1.52 on the H - T plane which is in contrast to the B -site Ti substituted MnCo 2 O 4 spinel that appears to follow irreversible non-mean-field AT-line behaviour (Φ ∼ 3 + δ ). Finally, the Arrott plots analysis indicates the presence of a pseudo first-order like transition ( T < 20 K) which is in consonance with and zero crossover of the magnetic entropy change within the frozen spin-glass regime., (© 2024 IOP Publishing Ltd.)

We report the experimental determination of the magnetic exchange parameter (J/kB= 2.88 ± 0.02 K) for the Spin-3/2 ferromagnetic (FM) Kagomé lattice system: Co 3 V 2 O 8 using the temperature dependence of dc-magnetic susceptibility χ ( T ) data by employing the fundamental Heisenberg linear chain model. Our results are quite consistent with the theoretically reported nearest neighbor dominant FM exchange coupling strengthJex-NN∼2.45 K. Five different magnetic phase transitions (6.2-11.2 K) and spin-flip transitions (9.6-7.7 kOe) have been probed using the∂(χT)/∂Tvs. T , heat capacity ( C P - T ) and differential isothermal magnetization curves. Among such sequence of transitions, the prominent ones being incommensurate antiferromagnetic (AFM) state at 11.2 K, commensurate AFM state at 8.8 K, and commensurate FM state across 6.2 K. All the successive magnetic phase transitions have been mapped onto a single H-T plane through which one can easily distinguish the above-mentioned different phases. The magnetic contribution of the C P - T near T N (11.2 K) has been analyzed using the power-law expressionCM=A|T-TN|-αresulting in the critical exponent α = 0.18 ± 0.01 (0.15 ± 0.003) for T < T N ( T > T N ), respectively for the Co 3 V 2 O 8 . It is interesting to note that non-Debye type dipole relaxation is quite prominent in Co 3 V 2 O 8 and was evident from the Kohlrausch-Williams-Watts analysis of complex modulus and impedance spectra (0⩽β⩽1). Mott's variable-range hopping of charge carriers process is evident through the resistivity analysis (ρac- T -1/4) in the temperature range 275  ∘ C-350  ∘ C. Moreover, the frequency-dependent analysis ofσac( ω ) follows Jonscher's power law yielding two distinct activation energies (Ea∼0.37 and 2.29 eV) between the temperature range 39  ∘ C-99  ∘ C and 240  ∘ C-321  ∘ C., (© 2024 IOP Publishing Ltd.)

Despite significant success, targeted therapeutics such as kinase inhibitors (KIs) still pose adverse events such as the cardiotoxicity. There is a lot of variation in the type and intensity of cardiotoxicity caused by different KIs and current pre-clinical models are inadequate to predict it. Thus, there is a need to develop more simple and rapid models for screening of novel KIs at the pre-clinical step itself. We thus aimed to establish a rapid and robust pre-clinical animal model for predicting cardiotoxicity of KIs and identify comparative cardiotoxicity profiles of a panel of FDA-approved KIs. Heart rate measurement and survival analysis of Daphnia was performed at regular intervals following treatment with ten KIs that were approved for the treatment of various cancers. The heart rates of Daphnia as well as the survival varied between KIs in a dose and time dependent manner suggesting differential cardiotoxicity profiles of various KIs. Further, the correlation between the cardiotoxicity and survival also varied among the ten KIs. Importantly, sorafenib and vemurafenib displayed maximum and least cardiotoxicity, respectively. The comparative cardiotoxicity profiles also are in conformity with the previous studies indicating the utility of Daphnia as a valuable and relevant animal model to rapidly predict the cardiotoxicity of novel KIs at a pre-clinical stage., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Here, we report the influence of Jahn-Teller active Cu substitution on the charge-ordering (CO) characteristics of one of the well-known manganite Pr 0.45 Sr 0.55 MnO 3 (S55) with a distorted tetragonal structure. Magnetization studies unveil a complex magnetic phase diagram for S55, showing distinct temperature ranges corresponding to various magnetic phases: a ferromagnetic phase dominated by the Double Exchange interaction with T C ∼ 220.5 K, an antiferromagnetic phase below T N ∼ 207.6 K induced by CO with a transition temperature of T CO ∼ 210 K consistent with the specific heat C P (T) data, and a mixed phase in the range T N < T < T CO due to the competitive interplay of these two interactions. Dilute substitution of Cu at the Mn B -sites disrupts the robust charge-ordered state, leading to enhanced ferrimagnetic order with T FN ∼273 K and significant magnetocrystalline anisotropy as confirmed by ferromagnetic resonance (FMR) studies. The Cu-substituted system displays a distinct cationic distribution compared to the pristine S55, contributing to its diverse magnetic structure. Our findings also reveal the irreversible metamagnetic transition ( H T-Max ∼ 8.85 kOe at 180 K) associated with the CO phenomena in S55 and the first-order nature of the phase transition across T CO . The magnetic heat capacity critical analysis ( C Mag = A ( T - T N ) - α ) yields the exponent, α = 0.097 (0.154) in the region T > T N ( T < T N ) consistent with the magnetic structure. The temperature dependence of FMR resonance field Δ H Res ( T ), peak-to-peak width H PP ( T ), and Gilbert damping factor α G ( T ) show clear anomalies across the magnetic transitions signifying the important role of admixtured (3+/4+) electronic state of Mn. Additionally, a strong correlation between the FMR α G (T) and switchable magnetic entropy change ( ΔS Max ∼ -8/+ 3 J kg -1 K -1 for ΔH = 90 kOe) has also been established in S55., (© 2024 IOP Publishing Ltd.)

Objective: This article introduces a novel approach called Digital Weighted Multi Criteria Decision Making (DWMCDM) that employs interval valued fuzzy sets to select the best contractor for building projects. The contractor is chosen based on the pre-qualification and bid evaluation phases. In the first phase, the distance between the actual and required skills of the significant criteria is determined, and it is then converted into digital weighted distances to identify the maximum number of criteria related to the specific project of each contractor. The second step ranks the best contractor based on the bid price and digital weighted distances., Results: The suggested technique integrates the pre-qualification and bid review phases to address project award delays and other restrictions. Finally, a real-world application is addressed to demonstrate the applicability of the proposed approach to any type of interval valued fuzzy inputs., (© 2024. The Author(s).)

Background: In this paper, we focus on an efficient and easy method for solving the given system of differential-algebraic equations (DAEs) of second order., Methods: The approximate solutions are computed rapidly and efficiently with the help of a semi-analytical method known as Adomian decomposition method (ADM). The logic of this method is simple and straightforward to understand., Results: To demonstrate the proposed method, we presented several examples and the computations are compared with the exact solutions to show the efficient. One can employ this logic to different mathematical software tools such as Maple, SCILab, Mathematica, NCAlgebra, Matlab etc. for the problems in real life applications., Conclusions: In this paper, we offered a method for solving the given system of secondorder nonlinear DAEs with aid of the ADM. We shown that the proposed method is simple and efficient, also one can obtain the approximate solutions quickly using this method. A couple of examples are discussed for illustrating this method and graphical and mathematical assessments are discussed with the analytical solutions of the given problems., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Thota S and P S.)