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Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review

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Journal of pharmaceutical Analysis 2024年第5期14卷 639-652页

作者： Hemanth p.R.Vikram Tegginamath pramod Kumar Gunjan Kumar Narasimha M.Beeraka Rajashree Deka sheik Mohammed suhail sandeep Jat Namitha Bannimath Gayatiri padmanabhan Ravandur s.Chandan pramod Kumar Bannimath Gurupadayya Department of pharmaceutical Chemistry JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Xenone Healthcare pvt.Ltd. New Delhi110076India Department of pharmaceutics JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Department of Human Anatomy I.M.Sechenov First Moscow State Medical University(Sechenov University)Moscow119991Russian Federation Department of pharmacology Raghavendra Institute of Pharmaceutical Education and Research(RIPER)Ananthapuramu515721India Herman B.Wells Center for pediatric Research Department of PediatricsIndiana University School of MedicineIndianapolisIN46202USA Animal physiology and Biochemistry Laboratory Department of ZoologyGauhati UniversityGuwahati781014India Department of pharmacology JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Department of pharmaceutical Analysis National Institute of Pharmaceutical Education and Research(NIPER)-GuwahatiChangsari781101India Department of pharmacology University of GalwayGalwayH91 TK33Ireland

The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic *** systematic review investigates their toxicity in active pharmaceutical ingredients(ApIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for *** review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological ***,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk *** comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

关键词： Carcinogenicity Genotoxicity Mutagenicity Molecular toxicity Nitrosamine impurities Nitrosamine drug substance-related impurities

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snapshot survey of the presence of perfluoroalkyl substances in products, Articles, and the Environment in Ecuador

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Engineering 2024年第6期37卷 49-61页

作者： Heidelore Fiedler Luis Vega-Bustillos Jenny Arias-pastrano Lander Vinicio pérez-Aldás Jose Castro-Díaz MTM Research Centre School of Science and TechnologyÖrebro UniversityÖrebro 70182Sweden Undersecretariat of Environmental Quality Ministry of EnvironmentWater and Ecological Transition of EcuadorQuito 170525Ecuador Department of Environmental Chemistry The Technical University of AmbatoHuachi CampusAmbato 180207Ecuador Alternativavision Ambiental Cia.Ltda. Mexico 03100Mexico

The stockholm Convention on persistent Organic pollutants(pOps)is a legally binding instrument for 186 parties(status:April 2023).Accordingly,among other responsibilities,countries are obliged to report the production,import,or export of the pOps listed in Annexes A,B,or C;provide information to registers;maintain inventories;and monitor the presence of pOps in the *** the broader context of international chemicals and waste management,producer responsibilities,harmonized reporting,and compliance with national and international regulations,Ecuador has addressed the newly listed group of perfluorinated alkyl substances(pFAs)in its national implementation plan and sent selected products from its national market for pFAs *** products analyzed came from the initially listed fields of specific exemptions and acceptable purposes,including:fire-fighting foams;photographic aids;greasers/degreasers;various kinds of paper/packaging;textiles;and leather,coatings,cleaners,metal plating,and *** results showed that the three pFAs presently listed in the stockholm Convention could be quantified in only a few samples;additional pFAs,not yet listed in the Convention also had low detection *** the number of samples was limited,the samples covered a large spectrum of sample matrices,making it possible to conclude that—once these products become waste and are regulated under the Basel Convention—they would not constitute a disposal ***,verification of the presence of pFAs in products on the market is expected to pose an analytical challenge for both,developed and developing countries.

关键词： Emerging or newly listed pOps stockholm Convention products and articles pFAs analysis Developing countries

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A novel diurnal and seasonal variation analysis of BTEX in Bengaluru urban area

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Research in Cold and Arid Regions 2024年第1期16卷 14-19页

作者： H.N.sowmya M.Dinamani G.p.shivashankara H.K.Ramaraju B.s.surendra Vijaya V.shanbhag R.prajwal Department of Civil Engineering Dayananda Sagar College of EngineeringBangalore 560078India Department of Chemistry Dayananda Sagar College of EngineeringBangalore 560078India Department of physics GFGCVijayanagarBengaluru 560040India

In the urban atmosphere of Bengaluru, various volatile organic compounds(VOCs), particularly Benzene,Toluene, Ethylbenzene, and Xylene(BTEX), have shown an increasing trend in concentration. The present research was conducted during summer and monsoon seasons, focusing on Kadubeesanahalli, a high-traffic area within the Bengaluru Metropolitan City. Hourly sample data was collected using a BTEX analyzer(Model GC955-600) and subsequently transformed into daily, monthly, and seasonal values. The study revealed distinct patterns in benzene concentrations. Benzene levels were lowest during the early morning hours, specifically from 1:00 *** 7:00 a.m.. Concentrations then increased from 7:00 a.m. to 9:00 a.m. and again from 4:00 p.m. to 11:00 p.m.,corresponding to the morning and evening peak traffic hours. However, between 10:00 a.m. and 4:00 p.m., the concentration decreased due to reduced traffic levels. These diurnal variations in benzene concentration are influenced by meteorological parameters. Comparing the two seasons, higher concentrations of Benzene, EthylBenzene, and Mp-xylene were observed during the summer season. This increase is attributed to the elevated temperatures during summer, which promote the vaporization of BTEX compounds. Conversely, lower BTEX concentrations were recorded during the monsoon season due to the wet deposition process. The observed positive correlation(r > 0.5) among BTEX parameters strongly suggests a common source, most likely originating from vehicular emissions.

关键词： BTEX summer variation Meteorological parameters Correlation

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On the analytical solution of transient friction in channel flows

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Applied Mathematics and Mechanics(English Edition) 2024年第8期45卷 1447-1466页

作者： F.J.GARCíA-GARCíA p.FARINAs-ALVARINO Department of Naval&Industrial Engineering Polytechnic School of EngineeringUniversity of A CorunaCampus Industrial de FerrolFerrol 15403A CorunaSpain Integraciones Técnicas de seguridad S.A.Pol.Ind.Espiritu SantoC/Nobel15Cambre 15650A CorunaSpain

The transient friction in channel mean flows is the sum of two contributions,i.e.,the underlying laminar flow(ULF)and the purely turbulent component(pTC),and the contributions are analyzed separately by theoretical *** is found that,the transient friction may be higher or remarkably lower than that in equal-Reynolds number steady-state *** universal time constant for plane-parallel laminar flows is reported,and the role of the time constant in a turbulent mean flow is *** is shown that the time constant is related to the turbulence's frozen ***,a study of the logarithmic layer during the transient flow is accomplished,which shows that the logarithmic layer is destroyed.

关键词： transient friction transient flow unsteady channel flow

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Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing

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Cellular & Molecular Immunology 2024年第4期21卷 362-373页

作者： Zeguang Wu Qiezhong Lamao Meichao Gu Xuanxuan Jin Ying Liu Feng Tian Ying Yu pengfei Yuan shuaixin Gao Thomas s.Fulford Adam p.Uldrich Catherine C.L Wong Wensheng Wei Biomedical pioneering Innovation Center Peking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University100871BeijingChina EdiGene Inc. Life Science ParkChangping District102206BeijingChina Center for precision Medicine Multi-Omics Research Peking University Health Science CenterPeking University100191BeijingChina Department of Microbiology and Immunology at the peter Doherty Institute for Infection and Immunity The University of MelbourneParkvilleVIC3010Australia Cancer Immunology program Peter MacCallum Cancer CentreMelbourneVICAustralia state Key Laboratory for Complex Severe and Rare DiseasesClinical Research InstitutePeking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences100871BeijingChina

Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate *** our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRIspR screening of cancer *** found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T *** coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX ***,an enzyme called QpCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer *** our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T ***,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.

关键词： Butyrophilin Vγ9Vδ2 T-cell Cancer-specific immune evasion Glutaminyl-peptide cyclotransferase-like pyrophosphate metabolite Immunotherapy

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Improved state-space Modelling for Microgrids Without Virtual Resistances

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Journal of Modern power systems and Clean Energy 2024年第2期12卷 584-596页

作者： paranagamage s.A.peiris shaahin Filizadeh Dharshana Muthumuni Department of Electrical and Computer Engineering University of ManitobaWinnipegMBR3T 5V6Canada Manitoba HVDC Research Center 211 Commerce DriveWinnipegMBR3P 1A3Canada IEEE

power converters and their interfacing networks are often treated as modular state-space blocks for small-signal stability studies in microgrids;they are interconnected by matching the input and output states of the network and *** resistors have been widely used in existing models to generate a voltage for state-space models of the network that require voltage *** paper accurately quantifies the adverse impacts of adding the virtual resistance and proposes an alternative method for network modelling that eliminates the requirement of the virtual resistor when interfacing converters with *** proposed nonlinear method allows initialization,time-domain simulations of the nonlinear model,and linearization and eigenvalue generation.A numerically linearized small-signal model is used to generate eigenvalues and is compared with the eigenvalues generated using the existing modelling method with virtual *** of the existing method and improvements offered by the proposed modelling method are clearly *** transient(EMT)simulations using detailed switching models are used for validation of the proposed modelling method.

关键词： Low-voltage converter state-space modelling dynamic phasor time-domain simulation eigenvalue analysis

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Explainable Conformer Network for Detection of COVID-19 pneumonia from Chest CT scan: From Concepts toward Clinical Explainability

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Computers, Materials & Continua 2024年第1期78卷 1171-1187页

作者： Mohamed Abdel-Basset Hossam Hawash Mohamed Abouhawwash s.s.Askar Alshaimaa A.Tantawy Faculty of Computers and Informatics Zagazig UniversityZagazig44519Egypt Department of Computational Mathematics Scienceand Engineering(CMSE)Michigan State UniversityEast LansingMI48824USA Department of Mathematics Faculty of ScienceMansoura UniversityMansoura35516Egypt Department of statistics and Operations Research College of ScienceKing Saud UniversityP.O.Box 2455Riyadh11451Saudi Arabia

The early implementation of treatment therapies necessitates the swift and precise identification of COVID-19 pneumonia by the analysis of chest CT *** study aims to investigate the indispensable need for precise and interpretable diagnostic tools for improving clinical decision-making for COVID-19 *** paper proposes a novel deep learning approach,called Conformer Network,for explainable discrimination of viral pneumonia depending on the lung Region of Infections(ROI)within a single modality radiographic CT ***,an efficient U-shaped transformer network is integrated for lung image ***,a robust transfer learning technique is introduced to design a robust feature extractor based on pre-trained lightweight Big Transfer(BiT-L)and finetuned on medical data to effectively learn the patterns of infection in the input ***,this work presents a visual explanation method to guarantee clinical explainability for decisions made by Conformer *** evaluation of real-world CT data demonstrated that the diagnostic accuracy of ourmodel outperforms cutting-edge studies with statistical *** Conformer Network achieves 97.40% of detection accuracy under cross-validation *** model not only achieves high sensitivity and specificity but also affords visualizations of salient features contributing to each classification decision,enhancing the overall transparency and trustworthiness of our *** findings provide obvious implications for the ability of our model to empower clinical staff by generating transparent intuitions about the features driving diagnostic decisions.

关键词： Deep learning COVID-19 multi-modal medical image fusion diagnostic image fusion

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A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications

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Bio-Design and Manufacturing 2024年第3期7卷 277-291页

作者： I.A.O.Beeren G.Dos santos p.J.Dijkstra C.Mota J.Bauer H.Ferreira Rui L.Reis N.Neves s.Camarero-Espinosa M.B.Baker L.Moroni Department of Complex Tissue Regeneration MERLN Institute for Technology-Inspired Regenerative MedicineMaastricht University6229 ER MaastrichtThe Netherlands 3B’s Research Group I3Bs–Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVs/3B’s-pT Government Associate Laboratory 4806-909 Braga/GuimarãesPortugal pOLYMAT University of the Basque Country UPV/EHU20018 Donostia/San SebastiánSpain IKERBAsQUE Basque Foundation for Science48009 BilbaoSpain

Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering ***,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell *** of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface ***,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(pCL5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight pCL75k at different *** porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight pCL *** a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).subsequently,a bone morphogenetic protein 2(BMp-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMsCs)was *** two weeks of culturing in a basic medium,cells expressed higher levels of BMp receptor II(BMpRII)on films with the conjugated *** addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface *** together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material ***,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(m

关键词： Additive manufacturing Blending surface functionalization surface density Click chemistry Human

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Anthropogenic Influence on Decadal Changes in Concurrent Hot and Dry Events over China around the Mid-1990s

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Advances in Atmospheric sciences 2024年第2期41卷 233-246页

作者： Qin sU Buwen DONG Fangxing TIAN Nicholas p.KLINGAMAN Yunnan Key Laboratory of Meteorological Disasters and Climate Resources in the Great Mekong subregion Yunnan UniversityKunming 650500China Department of Atmospheric sciences Yunnan UniversityKunming 650500China National Centre for Atmospheric science Department of MeteorologyUniversity of ReadingReadingRG66BBUK Geofysisk Institut University of BergenBergen 5007Norway Citadel Investment Group Moor House120 London WallLondonRG66BBUK

The frequency and duration of observed concurrent hot and dry events(HDEs) over China during the growing season(April–september) exhibit significant decadal changes across the mid-1990s. These changes are characterized by increases in HDE frequency and duration over most of China, with relatively large increases over southeastern China(sEC), northern China(NC), and northeastern China(NEC). The frequency of HDEs averaged over China in the present day(pD,1994–2011) is double that in the early period(Ep, 1964–81);the duration of HDEs increases by 60%. Climate experiments with the Met Office Unified Model(MetUM-GOML2) are used to estimate the contributions of anthropogenic forcing to HDE decadal changes over China. Anthropogenic forcing changes can explain 60%–70% of the observed decadal changes,suggesting an important anthropogenic influence on HDE changes over China across the mid-1990s. single-forcing experiments indicate that the increase in greenhouse gas(GHG) concentrations dominates the simulated decadal changes,increasing the frequency and duration of HDEs throughout China. The change in anthropogenic aerosol(AA) emissions significantly decreases the frequency and duration of HDEs over sEC and NC, but the magnitude of the decrease is much smaller than the increase induced by GHGs. The changes in HDEs in response to anthropogenic forcing are mainly due to the response of climatological mean surface air temperatures. The contributions from changes in variability and changes in climatological mean soil moisture and evapotranspiration are relatively small. The physical processes associated with the response of HDEs to GHG and AA changes are also revealed.

关键词： concurrent hot and dry events decadal variation greenhouse gases aerosol emissions

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In-situ study of the microstructure evolution during tension of a Mg-Y-Zn-Al alloy processed by rapidly solidified ribbon consolidation technique

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Journal of Magnesium and Alloys 2024年第5期12卷 2024-2040页

作者： Jeno Gubicza Kristián Máthis péter Nagy péter Jenei Zoltán Hegedus Andrea Farkas Jozef Vesely shin-ichi Inoue Daria Drozdenko Yoshihito Kawamura Department of Materials physics Faculty of ScienceEotvos Loránd UniversityPázmány P.sétány 1/ABudapest H-1117Hungary Department of physics of Materials Faculty of Mathematics and PhysicsCharles UniversityKe Karlovu 512116 Praha 2Czech Republic Deutsches Elektronen-synchrotron DEsY Notkestr.85Hamburg 22603Germany Magnesium Research Center Kumamoto University2-39-1 KurokamiChuo-kuKumamoto 860-8555Japan

Mg-Y-Zn-Al alloys processed by rapidly solidified ribbon consolidation(RsRC)technique exhibit an exceptional mechanical performance indicating promising application *** material has a bimodal microstructure consisting of fine recrystallized and coarse non-recrystallized grains with solute-rich stacking faults forming cluster arranged layers(CALs)and nanoplates(CANaps),or complete long period stacking ordered(LpsO)*** order to reveal the deformation mechanisms,in-situ synchrotron X-ray diffraction line profile analysis was employed for a detailed study of the dislocation arrangement created during tension in Mg-0.9%Zn-2.05%Y-0.15%Al(at%)*** uncovering the effect of the initial microstructure on the mechanical performance,additional samples were obtained by annealing of the as-consolidated specimen at 300 and 400℃ for 2 *** heat treatment at 300℃ had no significant effect on the initial microstructure,its evolution during tension and,thus,the overall deformation behavior under tensile *** the other hand,annealing at 400℃ resulted in a significant increase of the recrystallized grains fraction and a decrease of the dislocation density,leading to only minor degradation of the mechanical *** maximum dislocation density at the failure of the samples corresponding to the plastic strain of 10-25% was estimated to be about 16-20×10^(14)m^(-2).The diffraction profile analysis indicated that most dislocations formed during tension were of non-basal and pyramidal types,what was also in agreement with the schmid factor values revealed independently from orientation *** was also shown that the dislocation-induced Taylor hardening was much lower below the plastic strain of 3% than above this value,which was explained by a model of the interaction between prismatic dislocations and CANaps/LpsO plates.

关键词： Mg-Zn-Y-Al alloy Long period stacking ordered(LpsO)phase Cluster arranged nanoplates(CANaps) Annealing Tension Dislocation density Hardening

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