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1
Wang, Shanshan, e Joe Wiart. "Sensor-Aided EMF Exposure Assessments in an Urban Environment Using Artificial Neural Networks". International Journal of Environmental Research and Public Health 17, n. 9 (28 aprile 2020): 3052. http://dx.doi.org/10.3390/ijerph17093052.
Abstract (sommario):
This paper studies the time and space mapping of the electromagnetic field (EMF) exposure induced by cellular base station antennas (BSA) using artificial neural networks (ANN). The reconstructed EMF exposure map (EEM) in urban environment is obtained by using data from EMF sensor networks, drive testing and information accessible in a public database, e.g., locations and orientations of BSA. The performance of EEM is compared with Exposure Reference Map (ERM) based on simulations, in which parametric path loss models are used to reflect the complexity of urban cities. Then, a new hybrid ANN, which has the advantage of sorting and utilizing inputs from simulations efficiently, is proposed. Using both hybrid ANN and conventional regression ANN, the EEM is reconstructed and compared to the ERM first by the reconstruction approach considering only EMF exposure assessed from sensor networks, where the required number of sensors towards good reconstruction is explored; then, a new reconstruction approach using the sensors information combined with EMF along few streets from drive testing. Both reconstruction approaches use simulations to mimic measurements. The influence of city architecture on EMF exposure reconstruction is analyzed and the addition of noise is considered to test the robustness of ANN as well.
2
Seo, Myung-Soon, Jae-Wook Choi, Kyung-Hee Kim e Hyung-Do Choi. "The Relationship between Risk Perception of Cell Phones and Objective Knowledge of EMF in Korea". International Journal of Environmental Research and Public Health 17, n. 19 (1 ottobre 2020): 7207. http://dx.doi.org/10.3390/ijerph17197207.
Abstract (sommario):
This study examines differences between the level of objective knowledge regarding radio-frequency electromagnetic fields (RF-EMF) and risk perception of cell phones in Korea. We also investigate the extent to which socio-demographic factors, perceived EMF exposure, objective knowledge regarding EMF, and psychological factors influence the risk perception of cell phones using hierarchical multiple regression. All 3393 study subjects completed a survey measuring the degree of risk perception of EMF. They were sampled in accordance with representative proportions of sex, age group, and region of residence as shown in the 2019 Resident Registration Population Statistics reported by Korea. The variables that have the most influence on risk perception of cell phones can be induced from the beta values for each variable: The subjective factor, perceived level of exposure to EMF (β = 0.253), was more strongly related to risk perception of cell phones than level of knowledge regarding EMF, an objective factor in this study. Of the psychological factors, Dreadfulness (β = 0.331), Personal knowledge (β = −174), and Familiarity (β = −089) influenced risk perceptions of cell phones; Controllability did not. On the risk cognition map, people though that it was easy to control risk related to Cell phone use in daily life, while risk related to High technology was uncontrollable.
3
Gonzalez-Rubio, Jesus, Alberto Najera e Enrique Arribas. "Comprehensive personal RF-EMF exposure map and its potential use in epidemiological studies". Environmental Research 149 (agosto 2016): 105–12. http://dx.doi.org/10.1016/j.envres.2016.05.010.
4
Pang, L., S. J. Decker e A. R. Saltiel. "Bombesin and epidermal growth factor stimulate the mitogen-activated protein kinase through different pathways in Swiss 3T3 cells". Biochemical Journal 289, n. 1 (1 gennaio 1993): 283–87. http://dx.doi.org/10.1042/bj2890283.
Abstract (sommario):
Both bombesin and epidermal growth factor (EGF) are potent mitogens in Swiss 3T3 cells that nonetheless have dissimilar receptor structures. To explore possible common intracellular events involved in the stimulation of cellular growth by these two peptides, we have evaluated the regulation of the mitogen-activated protein (MAP) kinase. Exposure of Swiss 3T3 cells to bombesin, EGF or the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) causes the rapid and transient stimulation of the enzyme activity. Pretreatment of cells with the protein kinase inhibitor H-7, or down-regulation of cellular protein kinase C by prolonged exposure to PMA, causes a decrease of over 90% in the activation of MAP kinase by bombesin. In contrast, these treatments have no effect on the stimulation of MAP kinase by EGF. The stimulation of MAP kinase activity by bombesin is dose-dependent, occurring over a narrow concentration range of the peptide. Both EGF and bombesin stimulate the phosphorylation of an immunoprecipitable MAP kinase protein migrating at 42 kDa on SDS/PAGE. Phosphoamino acid analysis of this phosphorylated protein reveals that EGF and bombesin stimulate phosphorylation on tyrosine, threonine and serine residues. Tyrosine phosphorylation of the enzyme, as evaluated by antiphosphotyrosine blotting of the immunoprecipitated protein, reveals that the time course of phosphorylation by both mitogens correlates with stimulation of enzyme activity. These results provide further evidence for the convergence of discrete pathways emanating from tyrosine kinase and G-protein-linked receptors in the regulation of MAP kinase.
5
Georgiou, Christos D., Electra Kalaitzopoulou, Marianna Skipitari, Polyxeni Papadea, Athina Varemmenou, Vassilios Gavriil, Evangelia Sarantopoulou, Zoe Kollia e Alkiviadis-Constantinos Cefalas. "Physical Differences between Man-Made and Cosmic Microwave Electromagnetic Radiation and Their Exposure Limits, and Radiofrequencies as Generators of Biotoxic Free Radicals". Radiation 2, n. 4 (22 settembre 2022): 285–302. http://dx.doi.org/10.3390/radiation2040022.
Abstract (sommario):
The critical arguments for radiofrequency radiation exposure limits are currently based on the principle that radio frequencies (RF) and electromagnetic fields (EMFs) are non-ionising, and their exposure limits are even 100-fold lower than those emitted from the Sun in the whole RF-EMF spectrum. Nonetheless, this argument has been challenged by numerous experimental and theoretical studies on the diverse biological effects of RF-EMF at much lower power density (W/m2) levels than today’s exposing limits. On the other hand, less attention has been given to counterarguments based on the differences in the physics concepts underlying man-made versus natural electromagnetic radiation (EMR) and on the fact that man’s biology has been adapted to the natural EMR levels reaching Earth’s surface at single EMF wavelengths, which are the natural limits of man’s exposure to EMFs. The article highlights the main points of interaction of natural and man-made radiation with biomatter and reveals the physical theoretical background that explains the effects of man-made microwave radiation on biological matter. Moreover, the article extends its analysis on experimental quantum effects, establishing the “ionising-like” effects of man-made microwave radiation on biological matter.
6
Kelleher, M. D., M. K. Abe, T. S. Chao, M. Jain, J. M. Green, J. Solway, M. R. Rosner e M. B. Hershenson. "Role of MAP kinase activation in bovine tracheal smooth muscle mitogenesis". American Journal of Physiology-Lung Cellular and Molecular Physiology 268, n. 6 (1 giugno 1995): L894—L901. http://dx.doi.org/10.1152/ajplung.1995.268.6.l894.
Abstract (sommario):
Abnormal growth of airway smooth muscle may play an important role in the pathogenesis of human airway diseases. Little is known about the proliferative responses of cultured airway smooth muscle cells, nor of the precise pathways responsible for mitogenesis in these cells. We assessed DNA synthesis, cell proliferation, and mitogen-activated protein (MAP) kinase activation in bovine tracheal myocytes after exposure to four potential mitogens: platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and 5-hydroxytryptamine (5-HT). Stimulation with either PDGF or IGF-1 induced substantial increases in DNA synthesis and cell number, as reflected by [3H]thymidine incorporation, flow cytometry, and methylene blue staining. Treatment with EGF or 5-HT, on the other hand, induced only modest DNA synthesis and no increase in cell number. Immunoblots and kinase renaturation assays of cell extracts demonstrated activation of both the 42- and 44-kDa MAP kinases within minutes of either PDGF, IGF-1, EGF, or 5-HT exposure. However, relative to EGF and 5-HT stimulation, late-phase MAP kinase activation was significantly greater after treatment with the mitogens PDGF and IGF-1. We conclude that in cultured bovine tracheal myocytes 1) PDGF and IGF-1 are potent mitogens; 2) MAP kinase may be activated subsequent to stimulation of either receptor tyrosine kinases (PDGF, EGF, IGF-1) or G protein-linked receptors lacking in known tyrosine kinase activity (5-HT); and 3) unsustained MAP kinase activation is insufficient for mitogenesis. Finally, the finding that mitogenicity correlates with the late phase of MAP kinase activation is consistent with the notion that sustained MAP kinase activation is important for bovine tracheal myocyte proliferation.
7
Gökmen, Uğur, Zübeyde Özkan e Sema Bilge Ocak. "Impact of the gamma and neutron attenuation behaviors on the functionally graded composite materials". Physica Scripta 96, n. 12 (1 dicembre 2021): 125326. http://dx.doi.org/10.1088/1402-4896/ac41ef.
Abstract (sommario):
Abstract Gamma-ray and neutron shielding properties of the AA6082 + TiO2 (0–50 wt%) functionally graded composite materials (FGCMs) were investigated using the PSD software. The values of the mean free path (MFP), half-value layer (HVL), linear attenuation coefficients (LAC), mass attenuation coefficient (MAC), tenth-value layer (TVL), exposure buildup factors (EBF), effective atomic number (Z eff ), effective conductivity (C eff ), and fast neutron removal cross-sections (FNRC) were found for the energy range between 0.015–15 MeV. The increase in the TiO2 content in the AA6082 composite material has raised the values of MAC and LAC. The calculations for the EBFs were carried out using the G-P fitting method for the energy range between 0.015–15 MeV and penetration depth of up to 40 mfp. The results revealed that HVL values ranged between 0.01–0.116 cm, TVL values ranged between 0.01–0.385 cm, FNRC values ranged between 7.918–10.017 cm−1, and C eff values ranged between 5.67 × 1010 and 9.85 × 1010 S m−1. The AA6082 + TiO2 (50%) composite material was observed to provide the maximum photon and neutron shielding capacity since it offered the highest Z eff , MAC, and FNRC values, and the lowest HVL value. In terms of several aspects, the research is considered original. Besides contributing to several technologies including nanotechnology and space technologies, present research’s results may contribute to nuclear technology.
8
Heasley, L. E., S. I. Senkfor, S. Winitz, A. Strasheim, I. Teitelbaum e T. Berl. "Hormonal regulation of MAP kinase in cultured rat inner medullary collecting tubule cells". American Journal of Physiology-Renal Physiology 267, n. 3 (1 settembre 1994): F366—F373. http://dx.doi.org/10.1152/ajprenal.1994.267.3.f366.
Abstract (sommario):
Mitogen-activated protein (MAP) kinase is a widely expressed protein serine/threonine kinase that serves as a convergence point for many signaling pathways including receptor tyrosine kinases, G protein-coupled receptors, and protein kinase C (PKC). The hormonal regulation of MAP kinase was studied in cultured established rat inner medullary collecting tubule (RIMCT) cells. Neither vasopressin nor beta-adrenergic agonists stimulated MAP kinase, despite clear stimulation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. In contrast, carbachol, ATP, and epidermal growth factor (EGF), which are known to antagonize vasopressin action in the RIMCT, stimulated the MAP kinase pathway. This stimulation was mimicked by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, which directly activates PKC. The potency with which EGF and carbachol activated MAP kinase was similar to the potency with which they inhibited vasopressin-stimulated cAMP accumulation. To assess the role of Gi proteins in these stimulatory events, RIMCT cells were pretreated with pertussis toxin to inhibit Gi-mediated signaling. Pertussis toxin did not influence ATP- or EGF-stimulated MAP kinase, but completely inhibited carbachol stimulation, suggesting that Gi proteins mediate muscarinic stimulation. Prolonged exposure of RIMCT cells to high phorbol ester concentrations to downregulate PKC ablated carbachol- and ATP-stimulated MAP kinase, but not EGF-stimulated MAP kinase, suggesting that PKC is a component of the network involved in MAP kinase activation by purinergic and muscarinic agonists. Investigation of the sidedness of the hormonal stimulations indicated that EGF-stimulated MAP kinase was highly polarized, occurring exclusively from the basolateral surface, whereas carbachol stimulated MAP kinase similarly from either cell surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)
9
Bevington, Michael. "The Prevalence of People With Restricted Access to Work in Man-Made Electromagnetic Environments". Journal of Environment and Health Science 5, n. 1 (18 gennaio 2019): 1–12. http://dx.doi.org/10.15436/2378-6841.19.2402.
Abstract (sommario):
Some surveys have identified people who have restricted access to work in environments with man-made electromagnetic exposures. This study attempts to determine their prevalence, an aspect not previously investigated in its own right. It is based on analyses of the two different types of surveys of people with Idiopathic Environmental Intolerance attributed to Electromagnetic Fields (IEI-EMF), or Electromagnetic Hyper-Sensitivity (EHS), either of the general population or of people with IEI-EMF/EHS. In addition, there are different definitions of IEI-EMF/EHS, with a range of subconscious, mild, moderate or severe symptoms, potentially leading in three stages to hyper-sensitivity. The current evidence is assessed as indicating that, in addition to subconscious sensitivity, the prevalence of IEI-EMF/EHS is between about 5.0 and 30 per cent of the general population for mild cases, 1.5 and 5.0 per cent for moderate cases and < 1.5 per cent for severe cases. The prevalence of people restricted in their access to work in a man-made electromagnetic environment is estimated at 0.65 per cent of the general population, at about 18% of the general population with moderate IEI-EMF/EHS. The estimate of 0.65% equates to 435,500 people in the UK’s population of 67 million. Some reasons for possible under-reporting are discussed. Adjustments can enable some people with this disability to remain in employment, suggesting that rates of restriction in access to work may fall as employers become aware of what adjustments are needed.
10
Lee, M., C. Hwang, J. Lee, H. Slavkin e D. Warburton. "TGF-beta isoforms differentially attenuate EGF mitogenicity and receptor activity in fetal lung mesenchymal cells". American Journal of Physiology-Lung Cellular and Molecular Physiology 273, n. 2 (1 agosto 1997): L374—L381. http://dx.doi.org/10.1152/ajplung.1997.273.2.l374.
Abstract (sommario):
To evaluate signaling interactions, combinations of epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) isoforms were applied to primary fetal mouse lung mesenchymal cells isolated at 16 days of gestation. The three isoforms of TGF-beta had similar mitogenic potentials, as assessed by thymidine incorporation (half-maximal effective concentration approximately 2 ng/ml). However, combined exposure to EGF and TGF-beta yielded an isoform-dependent attenuation of EGF-induced mitogenesis. Combinations of 20 ng/ml EGF and 2 ng TGF-beta 1, TGF-beta 2, or TGF-beta 3 resulted in thymidine incorporation values 0.76, 0.74, and 0.86 times that of EGF alone, respectively; attenuation of EGF mitogenicity, interactions between EGF and TGF-beta isoforms, and differences between isoforms were all statistically significant by analysis of variance. Treatment with TGF-beta isoforms significantly reduced EGF-induced receptor angiotensin II substrate phosphorylation. TGF-beta isoform-specific signaling also significantly attenuated EGF-induced phosphorylation of the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase 2. These results suggest that isoform-specific TGF-beta signaling modulates the EGF signal transduction pathway upstream of MAP kinase.
11
SUDBECK, Barry D., Petra BAUMANN, Gavin J. RYAN, Katja BREITKOPF, Roswitha NISCHT, Thomas KRIEG e Cornelia MAUCH. "Selective loss of PMA-stimulated expression of matrix metalloproteinase 1 in HaCaT keratinocytes is correlated with the inability to induce mitogen-activated protein family kinases". Biochemical Journal 339, n. 1 (25 marzo 1999): 167–75. http://dx.doi.org/10.1042/bj3390167.
Abstract (sommario):
Many cell types, including fibroblasts and primary keratinocytes, increase matrix metalloproteinase 1 (MMP-1) production in response to agonists such as growth factors and phorbol esters. However, the spontaneously transformed human keratinocyte cell line HaCaT, although it increases MMP-1 production in response to epidermal growth factor (EGF), does not respond similarly to stimulation with PMA. This phenomenon occurs even though HaCaT cells remain proliferatively responsive to both agonists, suggesting a HaCaT-specific defect in a PMA-mediated signal transduction pathway. Using an inside-out approach to elucidate the source of this defect, we found that EGF, but not PMA, stimulated MMP-1 promoter activity in transiently transfected HaCaT keratinocytes. In addition, an assessment of fibroblast and HaCaT c-fos and c-jun gene expression after exposure to EGF and PMA showed that although both agonists increased the expression of c-fos and c-jun mRNA in fibroblasts, only EGF did so in HaCaT keratinocytes. Finally, we looked at the activation of mitogen-activated protein (MAP) family kinases after stimulation with EGF or PMA and found that both agonists increased the phosphorylation and activation of fibroblast extracellular signal-regulated protein kinase and c-Jun N-terminal kinase, but only EGF activated the same kinase activities in HaCaT cells. Further, the EGF-mediated increase in MMP-1 gene expression was inhibited by the MAP kinase/ERK kinase (MEK)-specific inhibitor PD98059 and the p38 kinase-specific inhibitor SB203580. Our evidence indicates that although HaCaT MAP kinases are functional, they are not properly regulated in response to the activation of protein kinase C, and that the defect that bars HaCaT MMP-1 expression in response to stimulation with PMA lies before MAP kinase activation.
12
Gosens, Reinoud, Gordon Dueck, William T. Gerthoffer, Helmut Unruh, Johan Zaagsma, Herman Meurs e Andrew J. Halayko. "p42/p44 MAP kinase activation is localized to caveolae-free membrane domains in airway smooth muscle". American Journal of Physiology-Lung Cellular and Molecular Physiology 292, n. 5 (maggio 2007): L1163—L1172. http://dx.doi.org/10.1152/ajplung.00471.2006.
Abstract (sommario):
Caveolae are abundant plasma membrane invaginations in airway smooth muscle that may function as preorganized signalosomes by sequestering and regulating proteins that control cell proliferation, including receptor tyrosine kinases (RTKs) and their signaling effectors. We previously demonstrated, however, that p42/p44 MAP kinase, a critical effector for cell proliferation, does not colocalize with RTKs in caveolae of quiescent airway myocytes. Therefore, we investigated the subcellular sites of growth factor-induced MAP kinase activation. In quiescent myocytes, though epidermal growth factor receptor (EGFR) was almost exclusively found in caveolae, p42/p44 MAP kinase, Grb2, and Raf-1 were absent from these membrane domains. EGF induced concomitant phosphorylation of caveolin-1 and p42/p44 MAP kinase; however, EGF did not promote the localization of p42/p44 MAP kinase, Grb2, or Raf-1 to caveolae. Interestingly, stimulation of muscarinic M2 and M3 receptors that were enriched in caveolae-deficient membranes also induced p42/p44 MAP kinase phosphorylation, but this occurred in the absence of caveolin-1 phosphorylation. This suggests that the localization of receptors to caveolae and interaction with caveolin-1 is not directly required for p42/p44 MAP kinase phosphorylation. Furthermore, we found that EGF exposure induced rapid translocation of EGFR from caveolae to caveolae-free membranes. EGFR trafficking coincided temporally with EGFR and p42/p44 MAP kinase phosphorylation. Collectively, this indicates that although caveolae sequester some receptors associated with p42/p44 MAP kinase activation, the site of its activation is associated with caveolae-free membrane domains. This reveals that directed trafficking of plasma membrane EGFR is an essential element of signal transduction leading to p42/p44 MAP kinase activation.
13
Grubbs, R. D. "Effect of epidermal growth factor on magnesium homeostasis in BC3H1 myocytes". American Journal of Physiology-Cell Physiology 260, n. 6 (1 giugno 1991): C1158—C1164. http://dx.doi.org/10.1152/ajpcell.1991.260.6.c1158.
Abstract (sommario):
The acute effects of epidermal growth factor (EGF) on Mg2+ homeostasis were studied in differentiated BC3H1 myocytes. EGF produced a 48-fold stimulation of [3H]thymidine incorporation into quiescent serum-starved cells in the presence of Mg2+, whereas insulin had no effect on [3H]thymidine incorporation. The dose dependence of EGF-stimulated [3H]thymidine incorporation was similar to that of EGF stimulation of 28Mg2+ uptake. In cells loaded with the Mg(2+)-sensitive fluorescent indicator, Mag-fura-2, intracellular Mg2+ concentration ([Mg2+]i) increased after exposure to EGF after a 5-min lag; a similar lag was routinely observed before the stimulation of 28Mg2+ uptake by EGF. In control studies, cytosolic free Ca2+ levels and intracellular pH (pHi) were unchanged during 20 min of exposure to EGF. These results suggest that [Mg2+]i in BC3H1 cells is regulated by EGF. This regulation is not mediated by changes in pHi or intracellular Ca2+ concentration and may constitute an important event in the physiological response of these cells to EGF. The results are discussed within the context of cellular regulation of Mg2+ homeostasis.
14
Larrivée, Jean-François, Dimcho R. Bachvarov, François Houle, Jacques Landry, Jacques Huot e François Marceau. "Role of the Mitogen-Activated Protein Kinases in the Expression of the Kinin B1 Receptors Induced by Tissue Injury". Journal of Immunology 160, n. 3 (1 febbraio 1998): 1419–26. http://dx.doi.org/10.4049/jimmunol.160.3.1419.
Abstract (sommario):
Abstract Several cytokines and LPS regulate the population of the B1 receptors (B1Rs) for kinins; these are responsive to des-Arg9-bradykinin (BK) and Lys-des-Arg9-BK. B1R activation contributes to inflammatory vascular changes and pain. Aortic rings isolated from normal rabbits and incubated in vitro in Krebs physiological medium were used as a model of tissue injury. From a null level of response, these rings exhibit a time- and protein synthesis-dependent increase in the maximal contractile response to des-Arg9-BK. Exposure to exogenous IL-1β or epidermal growth factor (EGF) considerably increases the process of sensitization to the kinins. Freshly isolated control aortic rings showed high mitogen-activated protein (MAP) kinase activities (persistent activation of p38, but less prolonged for extracellular signal-regulated kinase and c-Jun-N-terminal kinase/stress-activated protein kinase pathways) relatively to the basal activities found in various types of cultured cells. IL-1β or EGF further increased the activities of the extracellular signal-regulated kinase and c-Jun-N-terminal kinase/stress-activated protein kinase MAP kinases. The inhibitor of the p38 MAP kinase, SB 203580 (10 μM), massively (∼75%) and selectively inhibited the spontaneous sensitization to des-Arg9-BK over 6 h. SB 203580 also significantly reduced the development of the response to des-Arg9-BK as stimulated by IL-1 or EGF. Both spontaneous and IL-1β-stimulated up-regulation of responsiveness to des-Arg9-BK were significantly inhibited by the MAP kinase extracellular signal-regulated kinase kinase 1 inhibitor PD 98059 (∼40%). The protein kinase inhibitors failed to inhibit protein synthesis and to acutely inhibit the contractile effect of des-Arg9-BK, suggesting that they do not influence B1 receptor transduction mechanisms. In cultured aortic smooth muscle cells stimulated with EGF, MAP kinase activation preceded B1R mRNA induction. Protein kinase inhibitors reveal the role of cell injury-controlled MAP kinase pathways, and singularly of the p38 pathway, in the induction of B1R.
15
Chen, P., H. Xie, M. C. Sekar, K. Gupta e A. Wells. "Epidermal growth factor receptor-mediated cell motility: phospholipase C activity is required, but mitogen-activated protein kinase activity is not sufficient for induced cell movement." Journal of Cell Biology 127, n. 3 (1 novembre 1994): 847–57. http://dx.doi.org/10.1083/jcb.127.3.847.
Abstract (sommario):
We recently have demonstrated that EGF receptor (EGFR)-induced cell motility requires receptor kinase activity and autophosphorylation (P. Chen, K. Gupta, and A. Wells. 1994. J. Cell Biol. 124:547-555). This suggests that the immediate downstream effector molecule contains a src homology-2 domain. Phospholipase C gamma (PLC gamma) is among the candidate transducers of this signal because of its potential roles in modulating cytoskeletal dynamics. We utilized signaling-restricted EGFR mutants expressed in receptor devoid NR6 cells to determine if PLC activation is necessary for EGFR-mediated cell movement. Exposure to EGF (25 nM) augmented PLC activity in all five EGFR mutant cell lines which also responded by increased cell movement. Basal phosphoinositide turnover was not affected by EGF in the lines which do not present the enhanced motility response. The correlation between EGFR-mediated cell motility and PLC activity suggested, but did not prove, a causal link. A specific inhibitor of PLC, U73122 (1 microM) diminished both the EGF-induced motility and PLC responses, while its inactive analogue U73343 had no effect on these responses. Both the PLC and motility responses were decreased by expression of a dominant-negative PLC gamma-1 fragment in EGF-responsive infectant lines. Lastly, anti-sense oligonucleotides (20 microM) to PLC gamma-1 reduced both responses in NR6 cells expressing wild-type EGFR. These findings strongly support PLC gamma as the immediate post receptor effector in this motogenic pathway. We have demonstrated previously that EGFR-mediated cell motility and mitogenic signaling pathways are separable. The point of divergence is undefined. All kinase-active EGFR mutants induced the mitogenic response while only those which are autophosphorylated induced PLC activity. U73122 did not affect EGF-induced thymidine incorporation in these motility-responsive infectant cell lines. In addition, the dominant-negative PLC gamma-1 fragment did not diminish EGF-induced thymidine incorporation. All kinase active EGFR stimulated mitogen-activated protein (MAP) kinase activity, regardless of whether the receptors induced cell movement; this EGF-induced MAP kinase activity was not affected by U73122 at concentrations that depressed the motility response. Thus, the signaling pathways which lead to motility and cell proliferation diverge at the immediate post-receptor stage, and we suggest that this is accomplished by differential activation of effector molecules.
16
Heasley, L. E., e G. L. Johnson. "The beta-PDGF receptor induces neuronal differentiation of PC12 cells." Molecular Biology of the Cell 3, n. 5 (maggio 1992): 545–53. http://dx.doi.org/10.1091/mbc.3.5.545.
Abstract (sommario):
Expression of the mouse beta-PDGF receptor by gene transfer confers PDGF-dependent and reversible neuronal differentiation of PC12 pheochromocytoma cells similar to that observed in response to NGF and basic FGF. A common property of the PDGF, NGF, and basic FGF-induced differentiation response is the requirement for constant exposure of cells to the growth factor. To test the hypothesis that a persistent level of growth factor receptor signaling is required for the maintenance of the neuronal phenotype, we examined the regulation of the serine/threonine-specific MAP kinases after either short- (10 min) or long-term (24 h) stimulation with growth factors. Mono Q FPLC resolved two peaks of growth factor-stimulated MAP kinase activity that coeluted with tyrosine phosphorylated 41- and 43-kDa polypeptides. MAP kinase activity was markedly stimulated (approximately 30-fold) within 5 min of exposure to several growth factors (PDGF, NGF, basic FGF, EGF, and IGF-I), but was persistently maintained at 10-fold above basal activity after 24 h only by the growth factors that also induce PC12 cell differentiation (PDGF, NGF, and basic FGF). Thus the beta-PDGF receptor is in a subset of tyrosine kinase-encoded growth factor receptors that are capable of maintaining continuous signals required for differentiation of PC12 cells. These signals include the constitutive activation of cytoplasmic serine/threonine protein kinases.
17
Falin, Rebecca, I. Elias Veizis e Calvin U. Cotton. "A role for ERK1/2 in EGF- and ATP-dependent regulation of amiloride-sensitive sodium absorption". American Journal of Physiology-Cell Physiology 288, n. 5 (maggio 2005): C1003—C1011. http://dx.doi.org/10.1152/ajpcell.00213.2004.
Abstract (sommario):
Receptor-mediated inhibition of amiloride-sensitive sodium absorption was observed in primary and immortalized murine renal collecting duct cell (mCT12) monolayers. The addition of epidermal growth factor (EGF) to the basolateral bathing solution of polarized monolayers reduced amiloride-sensitive short-circuit current ( Isc) by 15–25%, whereas the addition of ATP to the apical bathing solution decreased Isc by 40–60%. Direct activation of PKC with phorbol 12-myristate 13-acetate (PMA) and mobilization of intracellular calcium with 2,5-di- tert-butyl-hydroquinone (DBHQ) reduced amiloride-sensitive Isc in mCT12 monolayers by 46 ± 4% ( n = 8) and 22 ± 2% ( n = 8), respectively. Exposure of mCT12 cells to EGF, ATP, PMA, and DBHQ caused an increase in phosphorylation of p42/p44 (extracellular signal-regulated kinase; ERK1/2). Pretreatment of mCT12 monolayers with an ERK kinase inhibitor (PD-98059; 30 μM) prevented phosphorylation of p42/p44 and significantly reduced EGF, ATP, and PMA-induced inhibition of amiloride-sensitive Isc. In contrast, pretreatment of monolayers with a PKC inhibitor (bisindolylmaleimide I; GF109203x; 1 μM) almost completely blocked the PMA-induced decrease in Isc, but did not alter the EGF- or ATP-induced inhibition of Isc. The DBHQ-mediated decrease in Isc was due to inhibition of basolateral Na+-K+-ATPase, but EGF-, ATP-, and PMA-induced inhibition was most likely due to reduced apical sodium entry (epithelial Na+ channel activity). The results of these studies demonstrate that acute inhibition of amiloride-sensitive sodium transport by extracelluar ATP and EGF involves ERK1/2 activation and suggests a role for MAP kinase signaling as a negative regulator of electrogenic sodium absorption in epithelia.
18
Liu, W., A. A. Akhand, M. Kato, I. Yokoyama, T. Miyata, K. Kurokawa, K. Uchida e I. Nakashima. "4-hydroxynonenal triggers an epidermal growth factor receptor-linked signal pathway for growth inhibition". Journal of Cell Science 112, n. 14 (15 luglio 1999): 2409–17. http://dx.doi.org/10.1242/jcs.112.14.2409.
Abstract (sommario):
Lipid peroxidation has been implicated in the pathogenesis of various diseases. As a major product of membrane lipid peroxidation, 4-hydroxynonenal (HNE) appears after various kinds of oxidative stress, and is known to induce cell growth inhibition. We here analysed the HNE-mediated signal transduction cascade for the growth inhibition of human epidermoid carcinoma A431 cells. HNE dose-dependently induced phosphorylation of multiple cellular proteins including epidermal growth factor receptor (EGFR) in A431 cells, and rapidly upregulated the catalytic actions of EGFR for autophosphorylation and for phosphorylation of casein as an exogenous substrate. Immunoblot analysis by use of HNE-specific antibody demonstrated the binding of HNE to EGFR along with its activation. This binding, which did not induce cross-linking of EGFR, caused a capping of the receptor on the cell surface which mimicked the capping induced by EGF. Phosphorylation and activation of EGFR were followed by phosphorylation of adaptor protein Shc and activation of MAP kinase. Both genistein as a wide spectrum protein tyrosine kinase inhibitor and AG1478 as a specific EGFR tyrosine phosphorylation blocker inhibited activation of EGFR and MAP kinase by HNE. The same inhibitors prevented HNE-mediated growth inhibition, suggesting a close linkage between EGFR/MAP kinase activation and growth inhibition after exposure to HNE. Our results suggest that EGFR may be one of the primary targets of HNE for an oxidative stress-linked cell growth inhibition.
19
Gibbons, Don L., Anna Ahn, Maofu Liao, Lena Hammar, R. Holland Cheng e Margaret Kielian. "Multistep Regulation of Membrane Insertion of the Fusion Peptide of Semliki Forest Virus". Journal of Virology 78, n. 7 (1 aprile 2004): 3312–18. http://dx.doi.org/10.1128/jvi.78.7.3312-3318.2004.
Abstract (sommario):
ABSTRACT A prevailing model for virus membrane fusion proteins has been that the hydrophobic fusion peptide is hidden in the prefusion conformation, becomes exposed once the fusion reaction is triggered, and then either inserts into target membranes or is rapidly inactivated. This model is in general agreement with the structure and mechanism of class I fusion proteins, such as the influenza virus hemagglutinin. We here describe studies of the class II fusion protein E1 from the alphavirus Semliki Forest virus (SFV). SFV fusion is triggered by low pH, which releases E1 from its heterodimeric interaction with the E2 protein and induces the formation of a stable E1 homotrimer. The exposure and target membrane interaction of the E1 fusion peptide (residues 83 to 100) were followed using a monoclonal antibody (MAb E1f) mapping to E1 residues 85 to 95. In agreement with the known structure of SFV and other alphaviruses, the fusion peptide was shielded in native SFV particles and exposed when E1-E2 dimer dissociation was triggered by acidic pH. In contrast, the fusion peptide on purified E1 ectodomains (E1*) was fully accessible at neutral pH. Functional assays showed that MAb E1f binding at neutral pH prevented subsequent low-pH-triggered E1* interaction with target membranes and trimerization. E1* was not inactivated by low pH when treated either in the absence of target membranes or in the presence of fusion-inactive cholesterol-deficient liposomes. Thus, the membrane insertion of the E1 fusion peptide is regulated by additional low-pH-dependent steps after exposure, perhaps involving an E1-cholesterol interaction.
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Mehta, Rajendra G. "Functional Significance of Selective Expression of ERα and ERβ in Mammary Gland Organ Culture". International Journal of Molecular Sciences 22, n. 23 (5 dicembre 2021): 13151. http://dx.doi.org/10.3390/ijms222313151.
Abstract (sommario):
Thoracic pair of mammary glands from steroid hormone-pretreated mice respond to hormones structurally and functionally in organ culture. A short exposure of glands for 24 h to 7,12 Dimethylbenz(a)anthracene (DMBA) during a 24-day culture period induced alveolar or ductal lesions. Methods: To differentiate the functional significance of ERα and ERβ, we employed estrogen receptor (ER) knockout mice. We compared the effects of DMBA on the development of preneoplastic lesions in the glands in the absence of ERα (αERKO) and ERβ (βERKO) using an MMOC protocol. Glands were also subjected to microarray analyses. We showed that estradiol can be replaced by EGF for pretreatment of mice. The carcinogen-induced lesions developed under both steroids and EGF pretreatment protocols. The glands from αERKO did not develop any lesions, whereas in βERKO mice in which ERα is intact, mammary alveolar lesions developed. Comparison of microarrays of control, αERKO and βERKO mice showed that ERα was largely responsible for proliferation and the MAP kinase pathways, whereas ERβ regulated steroid metabolism-related genes. The results indicate that ERα is essential for the development of precancerous lesions. Both subtypes, ERα and Erβ, differentially regulated gene expression in mammary glands in organ cultures.
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Ehab, Mohamed, Elsayed Salama, Ahmed Ashour, Mohamed Attallah e Hosam M. Saleh. "Optical Properties and Gamma Radiation Shielding Capability of Transparent Barium Borosilicate Glass Composite". Sustainability 14, n. 20 (16 ottobre 2022): 13298. http://dx.doi.org/10.3390/su142013298.
Abstract (sommario):
In this study, both radiation shielding capability and optical properties of prepared SiO2-ZnO-Na2CO3-H3BO3-BaCO3 glass composite with different concentrations of barium carbonate (0–30 mol%) have been studied. Gamma attenuation properties, such as the mass attenuation coefficient (MAC), mean free path (MFP), and exposure build-up factor (EBF), are experimentally and theoretically investigated. The detected XRD patterns for the prepared glass composites confirm their amorphous nature. It is evident from the obtained data that all tested parameters, such as mass density, molar volume, refractive index, dielectric constant, refraction loss (%), and molar refraction, have been increased as BaCO3 mol% increased. At the same time, the results of the optical bandgap show a gradual decrease with increasing barium concentration. It was also found that the mass attenuation coefficients increased with BaCO3 concentration from 0.078 at zero mol% BaCO3 to 0.083 cm2/g at 30 mol%. Moreover, the half-value layer (HVL) and the exposure build-up factor (EBF) up to 40 mfp penetration depth were investigated in addition to the effective atomic number (Zeff) and the corresponding equivalent atomic number (Zeq) at the energy range of 0.015–15 MeV. The produced glass composite might be considered for many shielding applications based on the obtained results that require a transparent shielding material.
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Ezzeldien, M., M. A. Salamab, M. F. Hasaneen, A. A. El-Maaref, M. M. Soraya, N. M. Shaalan, Z. A. Alrowaili e M. Ahmad. "Multicomponent Ge-As-Te-Pb chalcogenide glasses for radiations shielding applications". Chalcogenide Letters 19, n. 12 (21 dicembre 2022): 939. http://dx.doi.org/10.15251/cl.2022.1912.939.
Abstract (sommario):
Phy-X/PSD online program is used to obtain various radiation shielding indices in a photon energy region located between 0.15 and 15 MeV for Ge25-As10-Te65-x-Pbx (x = 2, 4, 6, 8, 10 at %) chalcogenide glasses. The linear attenuation coefficient LAC, mass attenuation coefficients MAC, effective atomic number Zeff, effective electron density Neff, half-value layer, HVL, tenth value layer TVL, mean free path MEF, energy absorption and exposure buildup factors (EABF, EBF), and fast neutron cross section FNRCS have been introduced. The findings conclude that the LAC and MAC measurements are greater and therefore better than commercial and traditional glasses. Also, it was found that HVL, TVL, and MFP were reduced with the addition of Pb to the tested glasses, which improve the shielding characteristics. Zeff and Neff of the compositions under study were varied as (42.58- 59.75) and (2.36-3.09 x 1023 electrons/g) respectively. A reduction was noticed in EBF and EABF values with the increment of Pb concentration in the investigated glasses at the entire photon energies, at all values of MFP that emphasize the enhancement of shielding properties of these glasses with the addition of lead. FNRCS were found to be changed between 0.87 and 0.095 Cm-1 as Pb content varies from 0.0 to 0.01 respectively that let these glasses
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Algethami, Merfat, Awad A. Ibraheem, Shams A. M. Issa, Huseyin O. Tekin, Antoaneta Ene, Maria Pyshkina, Mohamed Rashad, Ghada ALMisned e Hesham M. H. Zakaly. "A Comprehensive Evaluation of the Attenuation Characteristics of Some Sliding Bearing Alloys under 0.015–15 MeV Gamma-Ray Exposure". Materials 15, n. 7 (27 marzo 2022): 2464. http://dx.doi.org/10.3390/ma15072464.
Abstract (sommario):
In this study, three different sliding bearing alloy samples were investigated in terms of their performance on attenuation characteristics and behavioral attitudes under 0.015–15 MeV gamma-ray exposure. Accordingly, different types of advanced calculation methods were utilized to calculate the radiation shielding parameters. Next, several gamma-ray shielding parameters and exposure rates in addition to fast neutron removal cross-section were determined. Furthermore, exposure and energy absorption buildup factors were determined by using G-P fitting method. Mass attenuation coefficients (MAC) values were recorded as 2.5246, 2.5703, and 2.5827 (cm2/g) for Alloy1, Alloy2, and Alloy3 samples at 15 MeV photon energy, respectively. At 40 mfp, the highest EBF values were reported as 1,376,274, 1,003,593, and 969,373 for Alloy1, Alloy2, and Alloy3 samples. The results of this extended investigation showed that the Alloy3 sample with the highest Pb reinforcement amount has superior shielding capability among the investigated samples. It can be concluded from the results that substitution of Pb with Bi in the recent alloy structure has a monotonic effect on different types of shielding parameters. Therefore, it can also be concluded that Pb is a remarkable tool for the improvement of the shielding properties of studied alloy structures.
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Ghazal, Ayman Abu, Rawand Alakash, Zainab Aljumaili, Ahmed El-Sayed e Hamza Abdel-Rahman. "Enhancing Gamma-Neutron Shielding Effectiveness of Polyvinylidene Fluoride for Potent Applications in Nuclear Industries: A Study on the Impact of Tungsten Carbide, Trioxide, and Disulfide Using EpiXS, Phy-X/PSD, and MCNP5 Code". Journal of Radiation Protection and Research 48, n. 4 (30 dicembre 2023): 184–96. http://dx.doi.org/10.14407/jrpr.2023.00213.
Abstract (sommario):
Background: Radiation protection is crucial in various fields due to the harmful effects of radiation. Shielding is used to reduce radiation exposure, but gamma radiation poses challenges due to its high energy and penetration capabilities.Materials and Methods: This work investigates the radiation shielding properties of polyvinylidene fluoride (PVDF) samples containing different weight fraction of tungsten carbide (WC), tungsten trioxide (WO<sub>3</sub>), and tungsten disulfide (WS<sub>2</sub>). Parameters such as the mass attenuation coefficient (MAC), half-value layer (HVL), mean free path (MFP), effective atomic number (<i>Z</i><sub>eff</sub>), and macroscopic effective removal cross-section for fast neutrons (Σ<i><sub>R</sub></i>) were calculated using the Phy-X/PSD software. EpiXS simulations were conducted for MAC validation.Results and Discussion: Increasing the weight fraction of the additives resulted in higher MAC values, indicating improved radiation shielding. PVDF–<i>x</i>WC showed the highest percentage increase in MAC values. MFP results indicated that PVDF–0.20WC has the lowest values, suggesting superior shielding properties compared to PVDF–0.20WO<sub>3</sub> and PVDF–0.20WS<sub>2</sub>. PVDF–0.20WC also exhibited the highest <i>Z</i><sub>eff</sub> values, while PVDF–0.20WS2 showed a slightly higher increase in <i>Z</i><sub>eff</sub> at energies of 0.662 and 1.333 MeV. PVDF–0.20WC has demonstrated the highest Σ<i><sub>R</sub></i> value, indicating effective shielding against fast neutrons, while PVDF–0.20WS2 had the lowest Σ<i><sub>R</sub></i> value. The Monte Carlo N-Particle Transport version 5 (MCNP5) simulations showed that PVDF–<i>x</i>WC attenuates gamma radiation more than pure PVDF, significantly decreasing the dose equivalent rate.Conclusion: Overall, this research provides insights into the radiation shielding properties of PVDF mixtures, with PVDF–<i>x</i>WC showing the most promising results.
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Fei, Xing, Chen Nan, You Zheng e Sun Ting. "A Novel Approach Based on MEMS-Gyro's Data Deep Coupling for Determining the Centroid of Star Spot". Mathematical Problems in Engineering 2012 (2012): 1–20. http://dx.doi.org/10.1155/2012/403584.
Abstract (sommario):
The traditional approach of star tracker for determining the centroid of spot requires enough energy and good shape, so a relatively long exposure time and stable three-axis state become necessary conditions to maintain high accuracy, these limit its update rate and dynamic performance. In view of these issues, this paper presents an approach for determining the centroid of star spot which based on MEMS-Gyro's data deep coupling, it achieves the deep fusion of the data of star tracker and MEMS-Gyro at star map level through the introduction of EKF. The trajectory predicted by using the angular velocity of three axes can be used to set the extraction window, this enhances the dynamic performance because of the accurate extraction when the satellite has angular speed. The optimal estimations of the centroid position and the drift in the output signal of MEMS-Gyro through this approach reduce the influence of noise of the detector on accuracy of the traditional approach for determining the centroid and effectively correct the output signal of MEMS-Gyro. At the end of this paper, feasibility of this approach is verified by simulation.
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Rubino, Christopher M., Lukas Stulik, Harald Rouha, Zehra Visram, Adriana Badarau, Scott A. Van Wart, Paul G. Ambrose, Matthew M. Goodwin e Eszter Nagy. "1388. Dose Discrimination for ASN100: Bridging from Rabbit Survival Data to Predicted Activity in Humans Using a Minimal Physiologically Based Pharmacokinetic (mPBPK) Model". Open Forum Infectious Diseases 5, suppl_1 (novembre 2018): S426. http://dx.doi.org/10.1093/ofid/ofy210.1219.
Abstract (sommario):
Abstract Background ASN100 is a combination of two co-administered fully human monoclonal antibodies (mAbs), ASN-1 and ASN-2, that together neutralize the six cytotoxins critical to S. aureus pneumonia pathogenesis. ASN100 is in development for prevention of S. aureus pneumonia in mechanically ventilated patients. A pharmacometric approach to dose discrimination in humans was taken in order to bridge from dose-ranging, survival studies in rabbits to anticipated human exposures using a mPBPK model derived from data from rabbits (infected and noninfected) and noninfected humans [IDWeek 2017, Poster 1849]. Survival in rabbits was assumed to be indicative of a protective effect through ASN100 neutralization of S. aureus toxins. Methods Data from studies in rabbits (placebo through 20 mg/kg single doses of ASN100, four strains representing MRSA and MSSA isolates with different toxin profiles) were pooled with data from a PK and efficacy study in infected rabbits (placebo and 40 mg/kg ASN100) [IDWeek 2017, Poster 1844]. A Cox proportional hazards model was used to relate survival to both strain and mAb exposure. Monte Carlo simulation was then applied to generate ASN100 exposures for simulated patients given a range of ASN100 doses and infection with each strain (n = 500 per scenario) using a mPBPK model. Using the Cox model, the probability of full protection from toxins (i.e., predicted survival) was estimated for each simulated patient. Results Cox models showed that survival in rabbits is dependent on both strain and ASN100 exposure in lung epithelial lining fluid (ELF). At human doses simulated (360–10,000 mg of ASN100), full or substantial protection is expected for all four strains tested. For the most virulent strain tested in the rabbit pneumonia study (a PVL-negative MSSA, Figure 1), the clinical dose of 3,600 mg of ASN100 provides substantially higher predicted effect relative to lower doses, while doses above 3,600 mg are not predicted to provide significant additional protection. Conclusion A pharmacometric approach allowed for the translation of rabbit survival data to infected patients as well as discrimination of potential clinical doses. These results support the ASN100 dose of 3,600 mg currently being evaluated in a Phase 2 S. aureus pneumonia prevention trial. Disclosures C. M. Rubino, Arsanis, Inc.: Research Contractor, Research support. L. Stulik, Arsanis Biosciences GmbH: Employee, Salary. H. Rouha, 3Arsanis Biosciences GmbH: Employee, Salary. Z. Visram, Arsanis Biosciences GmbH: Employee, Salary. A. Badarau, Arsanis Biosciences GmbH: Employee, Salary. S. A. Van Wart, Arsanis, Inc.: Research Contractor, Research support. P. G. Ambrose, Arsanis, Inc.: Research Contractor, Research support. M. M. Goodwin, Arsanis, Inc.: Employee, Salary. E. Nagy, Arsanis Biosciences GmbH: Employee, Salary.
27
Horváthová, Martina, Zuzana Bárdyová, Darina Budošová e Rastislav Husťak. "Impact of methodical guidelines of gastric scintigraphy on patients’ radiation exposure". Gastroenterologie a hepatologie 75, n. 2 (30 aprile 2021): 159–64. http://dx.doi.org/10.48095/ccgh2021159.
Abstract (sommario):
Introduction: Gastric emptying scintigraphy (GES) is a safe, noninvasive method for assessing the ability of the stomach to empty which has been used clinically for many years. It is considered as a “gold standard” to assess gastric emptying of both solids and liquids allowing assessment of early, mid and late emptying, each of which may be altered by pathology. The aim of the study was to analyse standard diagnostic approach and evaluate patients` radiation exposure, who underwent GES in Slovakia. Methods: A retrospective cohort study included 55 patients from 2 departments of nuclear medicine (department A, B). Patients’ radiation exposure was determined by dosimetry program IDAC-Dose2.1. The radiopharmaceutical 99mTc-DTPA, always with the same activity, was applied orally to patients at Department B. The applied activity of the radiopharmaceutical at GES was 185 MBq. The radiopharmaceutical 99mTc MAA, with various activity, was applied orally to patients at Department A. Results: According to ICRP60, the eff ective dose (ED) of every patient undergoing GES was 0.77 mSv and, according to ICRP103, the dose was 0.836 mSv at Department B. Patients at Department A were exposed to ionizing radiation with 5-times lower intensity, compared with patients at Department B. It was caused by radiopharmaceutical activity correction. The ED medians according to ICRP60, and according to ICRP103 were 0.167 mSv (range 0.105–0.208 mSv) and 0.181 mSv (range 0.113–0.226 mSv) at Department A, respectively. Discussion: Adequate correction of applied radiopharmaceutical activity is an essential part of GES guidelines and in accordance with ALARA principles. For the accuracy of GES examination, it is necessary to follow a standard 4-hour protocol and an approach which ensures full-featured utilization of the examination while decreasing patient`s radiation exposure. Conclusion: The results of our study show relatively low ED associated with GES, but also confi rm that the GES methodology significantly affects the patient`s radiation exposure
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Elsafi, Mohamed, M. F. Alrashedi, M. I. Sayyed, Ibrahim F. Al-Hamarneh, M. A. El-Nahal, Mostafa El-Khatib, Mayeen Uddin Khandaker, Hamid Osman e Ahmad El Askary. "The Potentials of Egyptian and Indian Granites for Protection of Ionizing Radiation". Materials 14, n. 14 (14 luglio 2021): 3928. http://dx.doi.org/10.3390/ma14143928.
Abstract (sommario):
This paper aims to study the radiation shielding characteristics and buildup factor of some types of granite in Egypt. The mass attenuation coefficient (MAC) for three types of granite (gandola, white halayeb, and red aswani) was experimentally determined, and the experimental results were validated by XCOM software. The relative deviation between the two methods does not exceed 3% in all discussed granite samples, which means that MAC calculated through the experimental and XCOM are in suitable agreement. The effective atomic number (Zeff) varies from 13.64 to 10.69, 13.68 to 10.59, and 13.45 and 10.66 for gandola, white halayeb, and red aswani, respectively. As well as the equivalent atomic number (Zeq) was calculated in a wide range of energy to deduce the exposure (EBF) and energy absorption (EABF) buildup factors for the studied granite materials. The linear attenuation coefficient (LAC), half-value layer (HVL), mean free path (MFP) were calculated at each investigated energy and showed that the most effective shielding ability at high energy was red aswani, while at low energy, the shielding ability was nearly constant for studied granites. The present study forms the first endeavor to obtain the radiation shielding properties of the studied materials to be used in practical applications.
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El-Qahtani, Z. M. H., E. R. Shaaban e M. M. Soraya. "Attenuation characteristics of high-energy radiation on As-Se-Sn chalcogenide glassy alloy". Chalcogenide Letters 18, n. 6 (giugno 2021): 311–26. http://dx.doi.org/10.15251/cl.2021.186.311.
Abstract (sommario):
The present work is mainly interested in the use of chalcogenide glass materials as shielding materials for the highly energetic radiations as X-rays and Gamma rays and particles of high energies as neutrons. The chalcogenide glass system concerned with this study is As40-Se60-x-Snx (x = 0, 5, 10, 15, 20 at %). Numerous radiation shielding factors have been deduced by the aid of Phy-X/PSD online software. This software enabled us to achieve the linear and mass attenuation coefficients (LAC, MAC), effective atomic number Zeff, effective electron density, Neff, half-value layer, HVL, tenth value layer TVL, mean free path MEF, energy absorption and exposure buildup factors (EABF, EBF) in photon energy range extended from 0.15 to 15 MeV. The most interesting findings are that the LAC and MAC values are more suitable for shielding purposes than that of some commercial and traditional glasses. Also the results refer to that HVL, TVL, and MFP decrease with the substitution of Selenium by Tin in the tested system, this decreasing is clearer at the medium and high range of photon energies, which indicate to the improvement of shielding features by the adding of Sn to these specimens. Zeff and Neff of these glasses were in the range (33.6- 40.6) and (2.5-2.86 x 1023 electrons/g) respectively. The results also point to that EBF and EABF decrease with further raising of Snpercentage in the investigated chalcogenide system at all the values of MFP at the hole range of the photon energy, that confirm with no doubt that the samples with higher ratios of Tin have better shielding ability than those of lower ratios of Tin in the investigated system. It is also found that FNRCS of the five investigated specimens is in between 0.0886 Cm-1 and 0.0943 Cm-1 that makes them promising protective materials against neutrons, when compared with other commercial and traditional glasses.
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Gouda, Mona M., Ahmed M. El-Khatib, Mahmoud I. Abbas, Shoaa Mofleh Al-Balawi e Mahmoud T. Alabsy. "Gamma Attenuation Features of White Cement Mortars Reinforced by Micro/Nano Bi2O3 Particles". Materials 16, n. 4 (14 febbraio 2023): 1580. http://dx.doi.org/10.3390/ma16041580.
Abstract (sommario):
This study aims to explore the radiation protection properties of white mortars based on white cement as a binder and Bi2O3 micro and nanoparticles in proportions of 15 and 30% by weight as replacement sand. The average particle size of micro- and nano-Bi2O3 was measured using a transmission electron microscope (TEM). The cross-sectional morphology and distribution of Bi2O3 within the samples can be obtained by scanning electron microscopy (SEM), showing that nanoscale Bi2O3 particles have a more homogeneous distribution within the samples than microscale Bi2O3 particles. The shielding parameters of the proposed mortars were measured using the HPGe detector at various γ-ray energies emitted by standard radioactive point sources 241Am, 133Ba, 60Co, 137Cs, and 152Eu. The experimental values of the prepared mortars’ mass attenuation coefficients (MAC) match well with those determined theoretically from the XCOM database. Other shielding parameters, including half value layer (HVL), tenth value layer (TVL), mean free path (MFP), effective electron density (Neff), effective atomic number (Zeff), equivalent atomic number (Zeq), and exposure buildup factor (EBF), were also determined at different photon energies to provide more shielding information about the penetration of gamma radiation into the selected mortars. The obtained results indicated that the sample containing 30% by weight of nano Bi2O3 has the largest attenuation coefficient value. Furthermore, the results show that the sample with a high concentration of Bi2O3 has the highest equivalent atomic numbers and the lowest HVL, TVL, MFP, and EBF values. Finally, it can be concluded that Bi2O3 nanoparticles have higher efficiency and protection compared to microparticles, especially at lower gamma-ray energies.
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Zahran, Heba Y., El Sayed Yousef, Mohammed S. Alqahtani, Manuela Reben, Hamed Algarni, Ahmad Umar, Hasan B. Albargi, Ibrahim S. Yahia e Nehal Sabry. "Analysis of the Radiation Attenuation Parameters of Cu2HgI4, Ag2HgI4, and (Cu/Ag/Hg I) Semiconductor Compounds". Crystals 12, n. 2 (17 febbraio 2022): 276. http://dx.doi.org/10.3390/cryst12020276.
Abstract (sommario):
This analysis aims to determine photon attenuation for five different ternary and binary iodide compounds using Phy-X/PSD software. For a broad range of photon energies between 0.015 and 15 MeV, the mass attenuation coefficient (MAC), linear attenuation coefficient (LAC), half-value layer (HVL), tenth-value layer (TVL), and mean free path (MFP) for the samples of Cu2HgI4, Ag2HgI4, CuI, AgI, and HgI were calculated. For illustration, the following values of TVL apply at 1 MeV: S1: 6.062 cm, S2: 6.209 cm, S3: 6.929 cm, S4: 6.897 cm, and S5: 4.568 cm. Some important parameters, such as total atomic cross-sections (ACS), electronic cross-sections (ECS), the effective atomic numbers (Zeff), effective electron density (Neff), and effective conductivity (Ceff) of the samples were also calculated. Additionally, exposure buildup factors (EBF) and energy-absorption buildup factor (EABF) were estimated. These data on the radiation characteristics of our samples could be useful for gamma attenuation. The HgI sample has the highest FNRCS values (0.0892) relative to the other tested samples showing good neutron attenuation features. The CuI sample shows low gamma attenuation features; in contrast, it shows high neutron attenuation features.
32
Anelechi, Madubuike Stella, Mailafia Samuel Egwu O. Godwin, Olabode H. Olatunde, Momoh A.Habiba, Ode O. Julius e Ramon-Yusuf S.Babatunde. "Phenotypic Identification of Citrobacter Isolates from Cloacal Swabs of Apparently Healthy Turtles at the River Banks in Lokoja, Kogi State, Nigeria". International Journal of Current Microbiology and Applied Sciences 11, n. 11 (10 novembre 2022): 117–25. http://dx.doi.org/10.20546/ijcmas.2022.1111.014.
Abstract (sommario):
Citrobacter species are opportunistic pathogens in humans that can lead to invasive disease, including infections of the urinary tract, respiratory tract, Central Nervous System, skin, and soft tissues. A total of 245 cloacal swab samples were collected from the cloaca of apparently healthy turtles and subjected to conventional biochemical tests. Presumptive identification on MacConkey Agar (MAC) and Xylose lysine deoxycholate agar (XLD) yielded 42.0% (103) on each medium, on Eosin Methylene Blue agar (EMB) yielded 21.6 % (53), and on Salmonella-Shigella agar yielded 9.8% (24) isolates while Indole test, Methyl Red, VogesProskauer, Citrate utilization test (IMVIC) and Aesculin hydrolysis tests conformed with the conventional biochemical reactions for Citrobacter. The MicrobactTM 24 E identification test performed on the 23 isolates yielded a prevalence rate of 47.8 % for Citrobacter. However, this study is therefore the first phenotypic study to confirm the presence of Citrobacter species in turtles from the River banks in Lokoja, the study location. Humans can contract the infection through exposure, handling and consumption of poorly cooked turtle meat. Control measures are therefore necessary especially during the handling of apparently healthy turtle, to ensure that proper hygienic measures are observed.
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Poudel, Jeevan, Basanta Subedi e Tika Ram Lamichhane. "Radiation Shielding Features of Glass Fiber Reinforced Cast Polyamide Using Phy-X/PSD and SRIM Software". Journal of Institute of Science and Technology 28, n. 2 (23 dicembre 2023): 71–80. http://dx.doi.org/10.3126/jist.v28i2.55428.
Abstract (sommario):
The utilization of various materials for their nuclear radiation shielding properties has been the subject of a growing number of research and development projects. In this study, the radiation shielding characteristics of E-glass fiber reinforced cast polyamide were evaluated. E-glass is a form of glass fiber frequently utilized as a reinforcement in various composite materials to provide more durability, stiffness, and strength. Samples S1-S7 were defined according to various compositions of E-glass fiber contents (SiO2, Al2O3, B2O3, MgO, CaO, Na2O and K2O) and cast polyamide (C12H22N2O2). Within the energy range 0.015-15 MeV, the shielding parameters: Linear attenuation coefficient (LAC), mass attenuation coefficient (MAC), half and tenth value layers (HVL, TVL), mean free path (mfp), effective atomic number (Zeff), atomic and electronic cross sections (ACS, ECS), fast neutron removal cross-section (FNRCS) and exposure buildup factor (EBF) were analyzed. E-glass fiber reinforced cast polyamide S7 (70% glass fiber content) exhibited higher values of LAC, MAC and Zeff and lower values of HVL, TVL, and mfp proving it to be a better radiation shielding material among the samples. An abrupt reduction in values of Zeff was discerned within the photoelectric absorption-dominant region, contrasted with a stable trend within the Compton scattering-dominant region, and a marginal elevation was noted in the pair production region. The maximum and minimum values of FNRCS were observed for samples S1 (10% glass fiber content) and S5 (50% glass fiber content) respectively. Hence, S1 would be the most effective material in fast neutron shielding. At 35 mfp penetration depth, the minimum EBF values belonged to S7 in lower and intermediate regions (0.015-3 MeV) whereas S1 showed the minimum values at higher energy regions (4-15 MeV). Furthermore, the mass stopping power (MSP) and projected range (PR) of the samples for alpha and proton particles were determined using SRIM-2008 codes. S7 exhibited better shielding features for alpha and proton particles with lower values of mass stopping power and projected range. The reinforcement of glass fiber in the cast polyamide has been noticed to have a significant impact on the shielding performance of polymer composites.
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Saleh, Hosam M., Ibrahim I. Bondouk, Elsayed Salama, Hazem H. Mahmoud, Khalid Omar e Heba A. Esawii. "Asphaltene or Polyvinylchloride Waste Blended with Cement to Produce a Sustainable Material Used in Nuclear Safety". Sustainability 14, n. 6 (17 marzo 2022): 3525. http://dx.doi.org/10.3390/su14063525.
Abstract (sommario):
The current research uses sustainable methods to preserve the environment, such as exploiting municipal or industrial waste that may harm the environment. The wreckage of polyvinyl chloride (PVC) pipes and asphaltene are used as additives to cement to improve its mechanical properties, while stabilizing the radioactive waste resulting from the peaceful uses of nuclear materials, or enhancing its radiation shielding efficiency. New composites of Portland cement with ground PVC or asphaltene up to 50% are investigated. Fast neutron removal cross-section (ƩR) and gamma shielding parameters, such as mass attenuation coefficient (MAC), half-value layer (HVL), effective atomic number (Zeff), and exposure build-up factor (EBF) at wide energy range and thickness, are determined. The compressive strength and apparent porosity of the examined composites are examined to test the durability of the prepared composites as stabilizers for radioactive waste. The obtained results show that the bulk density of hardened cementitious composites was slightly increased by increasing the additive amount of PVC or asphaltene. The compressive strength of cement composites reached more than 4.5 MP at 50 wt.% PVC and 8.8 MPa at 50 wt.% asphaltene. These values are significantly higher than those recommended by the US Nuclear Regulatory Commission (3.4 MPa). Additionally, the obtained results demonstrate that although the gamma MAC is slightly decreased by adding asphaltene or PVC, the neutron removal cross-section was highly increased, reaching 171% in the case of 50 wt.% asphaltene and 304% in the case of 50 wt.% PVC. We can conclude that cement composites with PVC or asphaltene have optimized radiation shielding properties and can stabilize radioactive waste.
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Bendell, Johanna C., Kian-Huat Lim, Mark E. Burkard, Samuel J. Klempner, Mark A. Socinski, Shirish M. Gadgeel, Karen L. Reckamp et al. "CRESTONE: Clinical study of response to seribantumab in tumors with neuregulin-1 (NRG1) fusions—A phase II study of the anti-HER3 mAb for advanced or metastatic solid tumors (NCT04383210)." Journal of Clinical Oncology 39, n. 3_suppl (20 gennaio 2021): TPS449. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.tps449.
Abstract (sommario):
TPS449 Background: NRG1 (Neuregulin-1) gene fusions are rare oncogenic drivers found in 0.2% of solid tumors, including lung, pancreatic, gallbladder, breast, ovarian, colorectal, neuroendocrine, and sarcomas. NRG1 is the predominant ligand of HER3 and to a lesser extent HER4. NRG1 fusion proteins retaining an active EGF-like domain drive tumorigenesis and proliferation through aberrant HER3 activation. Importantly, NRG1 fusions are often mutually exclusive with other known driver alterations. NRG1 fusions have been correlated with worse overall and disease-free survival and poor response to treatment with standard therapies including chemotherapy, PD-(L)1 checkpoint inhibitors and combinations of these agents. Inhibition of HER3 and its dimerization partners represents a rational and novel therapeutic approach for tumors harboring an NRG1 fusion supported by case studies of clinical responses to anti-HER3 antibodies or pan-ERBB (tyrosine kinase inhibitors) TKIs like afatinib. Seribantumab is a fully human IgG2 mAb against HER3 uniquely able to inhibit NRG1-dependent activation of HER3, HER3-HER2 dimerization, and downstream signaling through the PI3K/AKT and MAPK pathways. The clinical safety profile of seribantumab has been well characterized through prior monotherapy and combination studies in over 800 patients. Methods: CRESTONE is an open label, multicenter phase 2 basket trial of seribantumab in adult patients with NRG1 fusion-positive locally advanced or metastatic solid tumors who have progressed on or are nonresponsive to available therapies. The trial will enroll at least 75 previously treated patients across three cohorts. Cohort 1 (N=55) will include patients who have not received prior treatment with any ERBB targeted therapy. Cohort 2 (up to N=10) will include patients who have progressed after prior treatment which includes ERBB targeted therapy. Cohort 3 (up to N=10) will include patients harboring NRG1 fusions without an EGF-like binding domain. NRG1 fusion status for enrollment will be determined through a local CLIA or similarly accredited molecular assay. NRG1 fusion status for patients in Cohort 1 will be centrally confirmed using an RNA-based NGS assay. This study will evaluate a novel dosing regimen of weekly induction, biweekly consolidation, and Q3W maintenance designed to rapidly achieve steady state levels, optimize exposure, and deliver maximal NRG1 inhibition. The primary endpoint is ORR per RECIST v1.1 by independent radiologic review. Secondary endpoints include duration of response (DoR), safety, PFS, OS, and overall clinical benefit rate. An interim analysis is planned following enrollment of 20 patients in Cohort 1. CRESTONE is open and accruing patients in the United States. Clinical trial information: NCT04383210.
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Takeda, Kotaro, Toshihiro Ichiki, Tomotake Tokunou, Satoshi Fujii, Akira Kitabatake e Akira Takeshita. "Critical Roles of Rho Kinase and Mek/Erk Pathways for Angiotensin Ii-Induced Plasminogen Activator Inhibitor-1 Gene Expression". Hypertension 36, suppl_1 (ottobre 2000): 721. http://dx.doi.org/10.1161/hyp.36.suppl_1.721-d.
Abstract (sommario):
P157 Plasminogen activator inhibitor-1 (PAI-1) plays an integral role not only in the regulation of plasminogen activity and fibrinolytic system but also in the pathogenesis of atherosclerosis and hypertension. Because angiotensin II (Ang II) is also involved in these processes, we investigated its role in the intracellular signaling cascade leading to PAI-1 gene expression in vascular smooth muscle cells (VSMC). Ang II increased the PAI-1 mRNA and protein levels through Ang II type 1 receptor. Although PAI-1 mRNA stability was not increased by Ang II, PAI-1 gene promoter activity, which was measured by luciferase assay, was significantly increased by Ang II. This process did not require de novo protein synthesis. BAPTA-AM, genistein and AG1478 completely inhibited the Ang II-induced PAI-1 mRNA upregulation, suggesting that intracellular calcium, tyrosine kinase and epidermal growth factor (EGF) receptor transactivation were involved in this process. However, inhibition of protein kinase C (PKC) by calphostin C, GF109203, or prolonged exposure to PMA failed to abolish the Ang II-induced PAI-1 upregulation, suggesting PKC pathway was not involved. PD98059 suppressed Ang II-induced PAI-1 upregulation, whereas SB203580 did not, suggesting that MEK/ERK1/2 pathway rather than p38 MAP kinase pathway was crucial in this process. Furthermore, adenovirus-mediated expression of dominant negative form of Rho kinase or Rho kinase inhibitor Y27632 also completely suppressed PAI-1 induction by Ang II without affecting Ang II-induced ERK1/2 activation. These data suggest that activation of both MEK/ERK1/2 and Rho kinase pathways will be necessary for the upregulation of PAI-1 gene expression and these two pathways may act synergically to promote PAI-1 gene transcription at least at the downstream of ERK1/2 in VSMC. These findings are important biological and therapeutical implications for the evolution of arterial wall thrombus and the pathogenesis of atherosclerosis by Ang II.
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Magyarics, Zoltan, Fraser Leslie, Steven A. Luperchio, Johann Bartko, Christian Schörgenhofer, Michael Schwameis, Ulla Derhaschnig et al. "Serum and Lung Pharmacokinetics of ASN100, a Monoclonal Antibody Combination for the Prevention and Treatment of Staphylococcus aureus Pneumonia". Open Forum Infectious Diseases 4, suppl_1 (2017): S310. http://dx.doi.org/10.1093/ofid/ofx163.722.
Abstract (sommario):
Abstract Background Monoclonal antibodies (mAbs) are well-suited for the prevention and treatment of acute bacterial infections. ASN100 is a combination of two fully human IgG1 mAbs, ASN-1 and ASN-2 that together neutralize six Staphylococcus aureus cytotoxins, alpha-hemolysin (Hla) and five leukocidins (HlgAB, HlgCB, LukED, LukSF [PVL] and LukGH) that are important in the pathogenesis of S. Aureus pneumonia. We aimed to characterize the pharmacokinetics (PK) of ASN100 in both serum and lung epithelial lining fluid (ELF) in male and female healthy volunteers. Methods The safety, tolerability, and serum and lung PK of single intravenous infusion of ASN100 was evaluated in a Phase 1 study. Eight subjects (3:1 randomization) in two double-blind cohorts received ASN100 (doses of 3600 mg or 8000 mg) or placebo. ASN-1 and ASN-2 were administered in a fixed dose 1:1 ratio. Twelve subjects received ASN100 open-label at doses of 3600 mg or 8000 mg and each underwent two bronchoalveolar lavage (BAL) fluid collections either on days 1 and 30 or on days 2 and 8 post-dosing. ASN-1 and ASN-2 concentrations were determined by ELISA. The ELF concentrations were normalized based on urea concentrations in serum and BAL fluid. Results No dose limiting toxicity was observed. Adverse events (AEs) showed no association of increased incidence with higher dose. All AEs were mild or moderate in severity, with 83.3% of subjects receiving ASN100 reporting at least one AE vs. 100% of placebo subjects. A dose proportional increase in serum peak and exposure (AUC) of ASN-1 and ASN-2 was observed and the serum PK of ASN-1 and ASN-2 were comparable (approximate half-life of each antibody was 3 weeks). Penetration of ASN-1 and ASN-2 into the ELF of the lung was observed at the first post-dose time point of 24 hours, peak concentrations were observed after day 2 and the mAbs remained detectable at day 30. Conclusion ASN100 was safe and well tolerated at doses up to 8000 mg (4000 mg ASN-1 and 4000 mg ASN-2). The PK profiles of ASN-1 and ASN-2 were comparable following simultaneous administration. Significant lung concentrations of each mAb were demonstrated between day 1 and 30 post-dosing. These data support continued clinical development of ASN100 for the prevention and treatment of S. Aureus pneumonia. Disclosures Z. Magyarics, Arsanis Biosciences GmbH: Employee, Salary. Arsanis, Inc.: Shareholder, Share options. F. Leslie, Arsanis., Inc.: Employee and Shareholder, Salary. S. A. Luperchio, Arsanis Inc.: Employee and Shareholder, Salary. B. Jilma, Arsanis Biosciences GmbH: Investigator, Investigator fee. C. Stevens, Arsanis Inc.: Employee and Shareholder, Salary.E. Nagy, Arsanis: Employee and Shareholder, Salary.
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von Achenbach, Caroline, Vincent Blot, William Weiss e Michael Weller. "CSIG-06. DEPATUXIZUMAB MAFODOTIN (ABT-414)-INDUCED GLIOBLASTOMA CELL DEATH REQUIRES EGFR OVEREXPRESSION, BUT NOT PHOSPHORYLATION". Neuro-Oncology 21, Supplement_6 (novembre 2019): vi45. http://dx.doi.org/10.1093/neuonc/noz175.177.
Abstract (sommario):
Abstract Glioblastomas commonly (40%) exhibit epidermal growth factor receptor (EGFR) amplification, half of these tumors carry the EGFRvIII deletion variant characterized by an in-frame deletion of exons 2–7, resulting in constitutive EGFR activation. Although EGFR tyrosine kinase inhibitors had only modest effects in glioblastoma, novel therapeutic agents targeting amplified EGFR or EGFRvIII continue to be developed. Depatuxizumab mafodotin (ABT-414) is an antibody drug conjugate consisting of the monoclonal antibody 806 and, as its toxic payload, monomethyl auristatin F, designed to target EGFR-overexpressing tumor cells. Since long-term glioma cell lines and patient-derived glioma-initiating cell lines appeared to express too little EGFR in vitro to be sensitive to ABT-414, we generated glioma sublines overexpressing EGFR or EGFRvIII to explore the determinants of ABT-414-induced glioma cell death. Overexpression of EGFRvIII induces sensitization to ABT-414 more readily than overexpression of EGFR. There is no bystander killing of cells devoid of EGFR or EGFRvIII expression. Surprisingly, either exposure to EGF or to EGFR tyrosin kinase inhibitors reduce EGFR protein levels and are thus no strategies to promote ABT-414-induced cell killing. Furthermore, glioma cells overexpressing kinase-dead EGFR or EGFRvIII retain binding of mAb 806 and sensitivity to ABT-414, allowing to dissociate EGFR phosphorylation from the emergence of the “active” EGFR conformation required for ABT-414 binding. The combination of EGFR-targeting antibody drug conjugates with EGFR tyrosine kinase inhibitors carries a high risk of failure. Promoting mere EGFR expression rather than phosphorylation should result in glioblastoma cell sensitization to ABT-414 or related agents.
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Machiels, J. H., S. Subramanian, A. Ruzsa, G. Repassy, I. Lifrenko, A. Flygare, P. Sorensen, E. Ehrnrooth, O. Baadsgaard e P. M. Clement. "An open-label, randomized, phase III trial of zalutumumab, a human monoclonal EGF receptor (EGFr) antibody, versus best supportive care, in patients with noncurable squamous cell carcinoma (SCCHN) of the head and neck who have failed standard platinum-based chemotherapy (ZALUTE)." Journal of Clinical Oncology 28, n. 18_suppl (20 giugno 2010): LBA5506. http://dx.doi.org/10.1200/jco.2010.28.18_suppl.lba5506.
Abstract (sommario):
LBA5506 Background: Zalutumumab is a novel, fully human IgG1 mAb targeting the EGFr that has shown encouraging activity in SCCHN. Methods: Patients with noncurable SCCHN with an ECOG PS of 0-2 and centrally documented radiographic progressive disease (PD) within 6 months after platinum-therapy were randomized between zalutumumab monotherapy and best supportive care (BSC) in a 2:1 ratio. Stratification parameter was ECOG PS. Methotrexate (MTX) was allowed in the BSC arm only. Individual dose-titration of zalutumumab was applied (max. exposure 16 mg/kg). The primary endpoint was overall survival (OS), with progression free survival (PFS) as the only secondary endpoint to be compared between groups, using log-rank test. 231 deaths were required to statistically differentiate OS between groups with 80% power. Results: 286 patients (34F, 252M) were randomized. The median age was 57 years (range 18-78), 65% had distant metastasis and 17% were ECOG PS 2, all similar between groups. 78% of patients in BSC arm received MTX. Although a median OS of 6.7 months was observed in the zalutumumab group compared to 5.2 in the BSC group, this was not statistically significant (p=0.065). A clear improvement in PFS (P=0.001) was demonstrated. Zalutumumab showed a safety profile as expected within this drug class. Conclusions: This is the first controlled study to demonstrate that an EGFr-targeted antibody given as monotherapy induces a clinically meaningful improvement in PFS in patients with SSCHN who have failed platinum-based chemotherapy. [Table: see text] [Table: see text]
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Mandakhalikar, Kedar Diwakar, Sang Seok Koh, Seong-Yun Jeong, Deborah Moshinsky, Peggy Feyaerts, Ratna Karuna, Jamie Kim et al. "First-in-class monoclonal antibody (mAb) PBP1510 targeting pancreatic adenocarcinoma upregulated factor (PAUF) for pancreatic cancer (PC) treatment: Preclinical perspectives." Journal of Clinical Oncology 40, n. 16_suppl (1 giugno 2022): e16274-e16274. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e16274.
Abstract (sommario):
e16274 Background: PAUF has been shown to induce PC cell proliferation, angiogenesis and evasion of immune surveillance, thereby promoting tumour progression and metastasis. PBP1510, a novel humanized IgG1 mAb developed by Prestige Biopharma Limited, Singapore, binds to and neutralizes PAUF with high specificity and affinity. With no available targeted therapies against PAUF, the first in its class, PBP1510, has been granted Orphan Drug Designation by EMA, US FDA and Korea MFDS. Methods: To assess inhibition of migration and invasion of PC in vitro, PC cell lines (CFPAC-1 and BxPC-3) with high expression levels of PAUF, and primary PC cells extracted from patients were treated with PBP1510 or human IgG (negative control). Suitability of cynomolgus monkey as animal model for pharmacokinetic (PK) and toxicity studies was verified by comparing binding affinities of PBP1510 to human and monkey PAUF. PK characteristics and immunogenicity of PBP1510 (up to 20 mg/kg), were examined in single dose studies in 6 monkeys. A 4-week repeated dose toxicity study was also conducted in 32 monkeys with PBP1510 (up to 40 mg/kg). An in vitro tissue cross-reactivity study was also conducted in a full panel of normal human tissues, to assess potential toxicity in humans. Results: PBP1510 suppressed the proliferation of the PC cell lines compared to negative control. The migration and invasion of PBP1510 treated PC cell lines as well as the primary tumour cells from patients was significantly reduced compared to the respective control groups in vitro. Similarity in binding affinity of PBP1510 to human PAUF and monkey PAUF, and amino acid sequence homology between human and monkey PAUF, suggest that monkey is an appropriate animal species for toxicity and PK studies of PBP1510. In monkey studies, a dose-proportional increase in systemic exposure was observed at low and high doses. PBP1510 at doses up to 40 mg/kg was well tolerated by study animals and no notable local or systemic toxicity was observed. Low immunogenic profile of PBP1510 was indicated by an absence of anti-PBP1510 antibodies till up to 57 days (8 doses and 28-day recovery period). These data are used to simulate human PK profile and to derive the starting dose and maximum escalated dose for the upcoming Phase 1 clinical studies. Cross-reactivity results did not reveal non-specific binding of PBP1510 in the human tissues except in the cytoplasm of acinar and duct epithelium in the salivary gland which is not expected to be of major toxicologic significance. Conclusions: The efficacy and safety data presented here, along with the data from in vivo mouse studies demonstrating superior anti-tumour activity of PBP1510 treatment, support further clinical development of PBP1510 as a novel anti-cancer agent to treat PAUF-positive PC. The pivotal step of advancing PBP1510 into initial human studies is now in progress.
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Fiskus, Warren C., Lucia Masarova, Christopher Peter Mill, Christine Birdwell, Kaberi Das, John Davis, Hanxi Hou et al. "Preclinical Studies Demonstrating Efficacy of Tasquinimod in Models of Advanced Myeloproliferative Neoplasm (MPN) in Blastic Phase". Blood 142, Supplement 1 (28 novembre 2023): 741. http://dx.doi.org/10.1182/blood-2023-185031.
Abstract (sommario):
The alarmins, S100A8 (A8) and S100A9 (A9), are low molecular weight proteins belonging to the S100 protein family. Also called calprotectins, A8 and A9 can form homodimers or heterodimers and bind Ca++. A8 and A9 are secreted into the extracellular space and plasma, where they interact with TLR4 (Toll like receptor 4), RAGE (Receptor for Advanced Glycation End products) and CD33. Intracellularly, they act as Ca++ biosensors and activate NADPH oxidase, stimulating ROS production, which activates NLRP3 inflammasome. A8 and A9 also amplify the inflammatory response through TLR4, and induce inflammatory cytokines, including TNFα and IL-6, through activation of NFkB and MAP kinase pathways. A8 and A9 are highly expressed in AML, especially myelomonocytic and monocytic AML, and are associated with poor prognosis. Through scRNA-Seq analysis, A8/A9 heterocomplex was shown to be highly expressed in myeloid and stromal cells and marked progression of bone marrow fibrosis in PMF (Primary Myelofibrosis). In the murine JAK2-V617F-driven PMF model, Tasquinimod (TM, Active Biotech), an orally active, quinoline-3-carboxamide linomide analogue immune-modulatory agent was shown to bind A9, inhibiting its interaction with TLR and RAGE receptors. Notably, TM treatment reduced myeloproliferation, splenomegaly and MF in JAK2-V617F mice. Therefore, based on these findings, in present studies, we determined in vitro and in vivo efficacy of TM against cellular models of advanced MPN cell lines and patient-derived (PD) CD34+ blastic phase (BP, > 5% blasts in PB) MPN cells. Treatment with TM (10 to 30 µM for 96 hours) induced loss of viability in the MPN-AML SET2, HEL92.1.7 cell lines and PD MPN-BP cells, but not in normal CD34+ progenitor cells. RNA-Seq analysis showed that exposure to TM (20 µM for 16 hours) led to negative enrichment of the gene-sets of MYC and E2F targets, of mTORC1 and IL6-JAK-STAT3 signaling, and of inflammatory response in PD MPN-AML cells. This was associated with log2 fold-decline in MYC, BCL2, CDK6, MPL, CCND1 and myeloperoxidase (MPO), but upregulation of mRNA of GFI1 and p21. CyTOF analysis revealed that TM treatment significantly reduced expressions of A8, A9, p-ERK, MPO, CXCR4, Cyclin D1, PU.1 and Ki67, but increased protein levels of GFI1, p21 and cleaved PARP in phenotypically defined PD, CD34+ MPN-BP cells expressing high levels of CLEC12A, CD99, CD123 but low expression of CD11b. Additionally, our findings showed that co-treatment with TM (5 to 30 µM) and ruxolitinib (250 to 1000 nM), BET inhibitor OTX015 (50 to 250 nM) or pelabresib (CPI-0610) (100 to 500 nM), or BCL2/Bcl-xL inhibitor navitoclax induced synergistic lethality in advanced MPN-BP cells exhibiting delta synergy scores of >1.0 (by the ZIP method). Notably, our findings also demonstrated that treatment with TM (10 or 30 mg/kg/day, by oral gavage) for 8-weeks, significantly improved survival without inducing any toxicity in immune-depleted NSG mice engrafted with PDX cells of MPN-AML with mutations in CALR and TERT. In a separate experiment on the same PDX model, treatment with TM (30 mg/kg/day) also induced significantly greater survival advantage than treatment with ruxolitinib (30 mg/kg/day) or OTX015 (30 mg/kg/day) by oral gavage. These findings clearly demonstrate preclinical efficacy of TM in advanced MPN-BP cellular models and create the rationale to further interrogate the efficacy of TM alone and in combinations with current, front-line therapies for advanced MPN with excess blasts.
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Koreth, John, Jerome Ritz, Leslie Chinn, Cherie Ng, Lisette M. Acevedo, Dalena Chu, Maple Fung et al. "Itolizumab, a Novel Targeted Anti-CD6 Therapy, in Combination with Corticosteroids, Is Well-Tolerated, with Rapid Pharmacodynamic and Clinical Response in Newly Diagnosed Acute Graft-Versus-Host Disease". Blood 138, Supplement 1 (5 novembre 2021): 2891. http://dx.doi.org/10.1182/blood-2021-145721.
Abstract (sommario):
Abstract Introduction: Itolizumab is a first-in-class monoclonal antibody against the co-stimulatory receptor CD6 that blocks its interaction with activated leukocyte cell adhesion molecule (ALCAM), thereby inhibiting T effector (T eff) cell activity and trafficking to target organs. It is being evaluated as a treatment for immuno-inflammatory diseases where T eff cells play a central role including acute graft-versus-host disease (aGVHD). Previous studies reported that ex vivo depletion of donor CD6+ cells in allogeneic hematopoietic cell transplantations lowers the incidence of aGVHD, justifying therapeutically targeting CD6 in aGVHD. Here we present interim clinical and pharmacokinetic/dynamic (PK/PD) results from the EQUATE study (NCT03763318), an ongoing US-based Phase 1b/2 study of itolizumab (a non-depleting anti-CD6 mAb) to treat subjects with newly diagnosed aGVHD, highlighting the relationship of early response to itolizumab concentrations. Methods: To date, 22 adult subjects with Grade III-IV aGVHD who initiated steroid treatment within 7 days prior to the first dose of itolizumab have enrolled in EQUATE at 0.4 mg/kg (n=4), 0.8 mg/kg (n=9), or 1.6 mg/kg (n=9), administered IV every 2 weeks x 5 doses. The median follow-up is 146 days (range: 14-355 days). Primary endpoints included itolizumab safety, tolerability, and optimal dose levels, and secondary endpoints included PK/ PD effects (change in CD6 surface expression on CD4+ cells) and clinical activity. Results: Patients: At baseline, study subjects had a mean (SD) age of 54 (14) and 68% were male; all had Grade III or IV aGVHD and 91% had lower GI involvement. All subjects received at least one dose and 15 received at least 2 doses of itolizumab. Safety: All subjects experienced at least 1 AE. Serious AEs occurred in 14 subjects (64%), with 9 (41%) reporting infection-related SAEs. There were 8 deaths. Six subjects (27.3%) had SAEs leading to death (3 at 0.8 mg/kg and 3 at 1.6 mg/kg): sepsis (n=1), Staphylococcal sepsis (n=1), Klebsiella sepsis (n=1), intestinal infarction (n=1), cardiac arrest (n=1), and GVHD (n=1). Another 2 deaths occurred >100 days post- last dose due to progressive aGVHD (n=1) and primary disease relapse (n=1). Efficacy and Survival: Across all doses, the complete response (CR) rate was 55% at both Day 15 and Day 29, and the overall response rate (ORR) was 73% at Day 15 and 68% at Day 29. At Day 169 (n=20), non-relapse mortality (NRM) was 35%, overall survival was 65%. Of note, the 10 subjects who achieved an early CR at Day 15 had a lower rate of NRM at Day 169 (20%) compared to the 10 subjects who had a very good partial response (VGPR), partial response (PR), no response (NR), or disease progression (50%). PK/PD: Itolizumab substantially decreased the levels of cell surface CD6 on circulating T cells after the first dose in a dose-dependent manner and maintained that decrease throughout the treatment period (Figure 1). Notable findings by immunophenotyping included: (1) an increase in the ratio of T regulatory to T eff cells at 0.8 and 1.6 mg/kg dose-level by Day 15, and (2) decreases of PD-1 expression on T cells and of ALCAM on CD14+ monocytes at all dose-levels by Day 8. This indicates itolizumab can reduce activation of T eff cells and monocytes. The relationship between drug concentrations and efficacy was evaluated at Day 15 when there was greater variability in response relative to later timepoints. Higher itolizumab trough concentrations on Day 15, achieved at higher dose-levels, correlated with a higher rate of CR at Day 15 (Figure 2). Conclusions: In summary, the observed safety, efficacy, PK and PD to date from this ongoing study indicate a favorable benefit-risk profile in subjects with Grade III-IV aGVHD. The relationship between itolizumab concentrations after the first dose and clinical response suggest that higher itolizumab exposures early (by Day 15) are impactful for longer term clinical responses. These data support the design and initiation of a pivotal phase 3, placebo-controlled clinical trial to assess itolizumab in combination with corticosteroids as first-line treatment of aGVHD. Figure 1 Figure 1. Disclosures Koreth: Equillium: Research Funding; Regeneron: Research Funding; Clinigen Labs: Research Funding; BMS: Research Funding; Miltenyi Biotec: Research Funding; Gentibio Inc.: Consultancy; EMD Serono/Merck: Consultancy; Amgen: Consultancy; Moderna: Consultancy; Cugene: Other: Scientific Advisory Board; Mallinckrodt: Other: Scientific Advisory Board; Biolojic Design: Other: Scientific Advisory Board. Ritz: Amgen: Research Funding; Equillium: Research Funding; Kite/Gilead: Research Funding; Avrobio: Membership on an entity's Board of Directors or advisory committees; Akron: Consultancy; Biotech: Consultancy; Blackstone Life Sciences Advisor: Consultancy; Clade Therapeutics, Garuda Therapeutics: Consultancy; Immunitas Therapeutic: Consultancy; LifeVault Bio: Consultancy; Novartis: Consultancy; Rheos Medicines: Consultancy; Talaris Therapeutics: Consultancy; TScan Therapeutics: Consultancy. Chinn: Equillium: Current Employment, Current equity holder in publicly-traded company; Principia Biopharma: Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; Genentech/Roche: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months, Patents & Royalties: Methods of treating immune diseases using an inhibitor of Bruton's tyrosine kinase (provisional patent application. Ng: Equillium: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Acevedo: Equillium: Current Employment, Current equity holder in publicly-traded company; Arena: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months. Chu: Equillium: Current Employment. Fung: Equillium: Current Employment; Arena: Ended employment in the past 24 months, Patents & Royalties. Rothman: Equillium: Current Employment, Current equity holder in publicly-traded company. Connelly: Equillium: Current Employment, Divested equity in a private or publicly-traded company in the past 24 months, Membership on an entity's Board of Directors or advisory committees. Thomas: Equillium: Current Employment, Current equity holder in publicly-traded company; Chinook: Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees; Principia: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Cutler: Deciphera: Consultancy; Cimeio: Consultancy; Editas: Consultancy; Kadmon: Consultancy; Pfizer: Consultancy; Mallinckrodt: Consultancy; CareDx: Consultancy; Incyte: Consultancy; Omeros: Consultancy; Syndax: Consultancy; Mesoblast: Consultancy; Jazz: Consultancy.
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Karipidis, Ken, Chris Brzozek, Chhavi Raj Bhatt, Sarah Loughran e Andrew Wood. "What evidence exists on the impact of anthropogenic radiofrequency electromagnetic fields on animals and plants in the environment? A systematic map protocol". Environmental Evidence 10, n. 1 (dicembre 2021). http://dx.doi.org/10.1186/s13750-021-00252-w.
Abstract (sommario):
Abstract Background Exposure to radiofrequency (RF) electromagnetic fields (EMF), particularly from telecommunications sources, is one of the most common and fastest growing anthropogenic factors on the environment. In many countries, humans are protected from excessive RF EMF exposure by safety standards that are based on guidelines by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). The ICNIRP guidelines are based on knowledge of how RF EMF affects the human body, however, there are currently no recognised international guidelines to specifically protect animals and plants. Whether the ICNIRP guidelines for humans is adequate to provide protection to the environment is a subject of active debate. This systematic map will collate all the available evidence on whether anthropogenic RF EMF has a negative effect on plants and animals in the environment. The map will also identify gaps in knowledge, recommend future research and inform environmental and radiation protection authorities. Methods The proposed systematic map will include peer-reviewed and grey literature published in English. The EMF—Portal, PubMed and Web of Science databases will be searched using a search string prepared by the review team and tested for comprehensiveness against a list of known relevant reviews. Once duplicates are removed, retrieved articles will be screened in three stages: title, abstract, and full text. Studies will be selected with a subject population of all plants and animals, with exposures to anthropogenic RF EMF (frequency range 100 kHz–300 GHz) compared to no or lower-level exposure, and for all outcomes related to the studied populations. Kappa statistic tests will be conducted at each stage to ensure consistency of decision-making regarding the predefined inclusion/exclusion criteria. Eligible studies will then proceed to the data extraction phase, which will extract meta-data such as bibliographic information, taxonomic information, RF EMF exposure data, outcome(s), sample size, etc. The extracted data will then be organised into a systematic map and the findings summarised by cross-tabulating key meta-data variables in heat maps, charts or other data visualization methods. The systematic map will identify gaps in knowledge, priorities for future research and potential subtopics for further analysis and/or systematic review.
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Karipidis, Ken, Chris Brzozek, Rohan Mate, Chhavi Raj Bhatt, Sarah Loughran e Andrew W. Wood. "What evidence exists on the impact of anthropogenic radiofrequency electromagnetic fields on animals and plants in the environment: a systematic map". Environmental Evidence 12, n. 1 (11 maggio 2023). http://dx.doi.org/10.1186/s13750-023-00304-3.
Abstract (sommario):
Abstract Background Exposure to radiofrequency (RF) electromagnetic fields (EMF), particularly from telecommunications sources, is one of the most common and fastest growing anthropogenic factors on the environment. In many countries, humans are protected from harmful RF EMF exposure by safety standards that are based on guidelines by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). The ICNIRP guidelines are based on knowledge of how RF EMF affects the human body, however, there are currently no recognised international guidelines to specifically protect animals and plants. Whether the ICNIRP guidelines for humans are adequate to provide protection to the environment is a subject of active debate. There is some public concern that new telecommunications technologies, like the 5G mobile phone network may affect the natural environment. This systematic map presents a searchable database of all the available evidence on whether anthropogenic RF EMF has an effect on plants and animals in the environment. The map also identifies gaps in knowledge, recommends future research and informs environmental and radiation protection authorities. Methods The method used was published in an a priori protocol. Searches included peer-reviewed and grey literature published in English with no time and geographic restrictions. The EMF-Portal, PubMed and Web of Science databases were searched, and the resulting articles were screened in three stages: title, abstract and full text. Studies were included with a subject population of all animals and plants, with exposures to anthropogenic RF EMF (frequency range 100 kHz–300 GHz) compared to no or lower-level exposure, and for any outcomes related to the studied populations. For each included study, metadata were extracted on key variables of interest that were used to represent the distribution of available evidence. Review findings The initial search, search update and supplementary searches produced 24,432 articles and of those 334 articles (237 on fauna and 97 on flora) that were relevant were included in the systematic map. The vast majority of studies were experiments conducted in a laboratory rather than observational studies of animals and plants in the natural environment. The majority of the studies investigated exposures with frequencies between 300 and 3000 MHz, and although the exposure level varied, it was mainly low and below the ICNIRP limits. Most of the animal studies investigated insects and birds, whereas grains and legumes were the most investigated plants. Reproduction, development and behaviour were the most investigated effects for animals, and germination and growth for plants. The vast majority of the studies employed poor quality methods. Conclusion There are distinct evidence clusters: for fauna, on insect and bird reproduction, development and behaviour; and for flora, grain and legume germination and growth that would benefit from specific systematic reviews. The systematic map also highlights the clear need for investigating the effects of RF EMF on more species and more types of effects, and for an improvement in the quality of all studies.
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Pawełek, Agnieszka, Samuel Acheaw Owusu, Daniele Cecchetti, Adrianna Zielińska e Joanna Wyszkowska. "What evidence exists of crop plants response to exposure to static magnetic and electromagnetic fields? A systematic map protocol". Environmental Evidence 11, n. 1 (6 dicembre 2022). http://dx.doi.org/10.1186/s13750-022-00292-w.
Abstract (sommario):
Abstract Background Increasing demand for food and concerns over the environmental impact of agriculture has prompted the search for alternatives to many conventional farming practices. Reports on exposing seeds and plants at various developmental stages to static magnetic field (SMF) and non-ionizing electromagnetic fields (EMF) as a form of priming indicate some positive effects on seed germinability, growth rate, resistance to stress conditions, and improved yield. However, there exist some inconsistent reported treatment protocols and contradictory study outcomes that make it difficult to draw objective conclusions on the potential use of SMF and EMF as sustainable alternatives to improving crop growth and yield. It is equally essential to understand any adverse effects of exposing plants to SMF and EMF considering the abundance of their sources in the environment. In order to provide a more coherent overview of how plants respond to exposure to SMF and EMF not only in their observed effects of agronomic importance but also in the mechanisms of action of SMF and EMF in plant cells, we prepare a systematic map. Methods Literature will be identified by searching six bibliographic databases and three web-based search engines using terms obtained from the population, exposure, and outcome parameters of the research question. Primary research published in peer-reviewed journals and grey literature will be the source for the evidence map. Studies eligible for inclusion may involve: food crops and related research model plants exposed to SMF or non-ionizing EMF; treatment at all plant developmental stages excluding post-harvest improvement of food crops; and the presence of control groups. Eligible literature will be screened at the title, abstract, and full text levels. The validity of studies will not be critically appraised for the evidence map. A process of double extraction and coding of relevant information from eligible literature will be conducted. Within the evidence map, relevant data will be presented in the forms of text, graphs, tables, and figures. This will illustrate research trends, bring clarity to the evidence base concerning clusters of sufficient findings and areas of significant gaps, and inform stakeholders in decisions concerning research planning and policy formulation.
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Malvandi, Hassan, e Nasrin Hassanzadeh. "Evaluation of Temporal and Spatial Distribution of Radio Frequency Electromagnetic Fields (RF-EMF) Exposure Levels in Sabzevar, Iran". Epidemiology and Public Health 1, n. 1 (8 settembre 2023). http://dx.doi.org/10.52768/epidemiolpublichealth/1003.
Abstract (sommario):
Objectives: In recent years, investigating the possibility of health risks due to exposure to radio frequency electromagnetic field (RF-EMF) values has become an important research priorities. The main study goal was to evaluate the temporal and spatial exposure levels of power density (S) from BTS antennas in Sabzevar city. In addition, this study investigated the difference in power density between the suburbs and downtown, as well as between different microenvironments. Methods: The power density values were measured at three distances from the BTS antennas and at three different time intervals. S values were measured using a TES 593 electrosmog meter. The General linear model repeated measurement tests and Mann-Whitney U test were used to measure the objectives. The Inverse Distance Weighted method was used to draw the spatial distribution map. Results: Significant differences between the values of S Avg and S max Avg were detected based on distance from the BTS antennas, time measured, and type of location. For hospital, residential, residential-educational, residential-park, and residential-shopping, the average values of S Avg were 0.37, 1.15, 1.80, 1.89, and 1.94 W/m2 , respectively, and the average values of S max Avg were 0.43, 2.64, 2.54, 2.59, and 2.64 W/ m2 , respectively. There was a significant difference between S Avg and S max Avg values by microenvironment. Conclusions: Comparison of the all of the measured values of S in this study with the limits set by multiple organizations indicated that the residents of Sabzevar city are not exposed to levels considered to pose a risk.
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Levitt, B. Blake, Henry C. Lai e Albert M. Manville. "Effects of non-ionizing electromagnetic fields on flora and fauna, Part 2 impacts: how species interact with natural and man-made EMF". Reviews on Environmental Health, 8 luglio 2021. http://dx.doi.org/10.1515/reveh-2021-0050.
Abstract (sommario):
Abstract Ambient levels of nonionizing electromagnetic fields (EMF) have risen sharply in the last five decades to become a ubiquitous, continuous, biologically active environmental pollutant, even in rural and remote areas. Many species of flora and fauna, because of unique physiologies and habitats, are sensitive to exogenous EMF in ways that surpass human reactivity. This can lead to complex endogenous reactions that are highly variable, largely unseen, and a possible contributing factor in species extinctions, sometimes localized. Non-human magnetoreception mechanisms are explored. Numerous studies across all frequencies and taxa indicate that current low-level anthropogenic EMF can have myriad adverse and synergistic effects, including on orientation and migration, food finding, reproduction, mating, nest and den building, territorial maintenance and defense, and on vitality, longevity and survivorship itself. Effects have been observed in mammals such as bats, cervids, cetaceans, and pinnipeds among others, and on birds, insects, amphibians, reptiles, microbes and many species of flora. Cyto- and geno-toxic effects have long been observed in laboratory research on animal models that can be extrapolated to wildlife. Unusual multi-system mechanisms can come into play with non-human species — including in aquatic environments — that rely on the Earth’s natural geomagnetic fields for critical life-sustaining information. Part 2 of this 3-part series includes four online supplement tables of effects seen in animals from both ELF and RFR at vanishingly low intensities. Taken as a whole, this indicates enough information to raise concerns about ambient exposures to nonionizing radiation at ecosystem levels. Wildlife loss is often unseen and undocumented until tipping points are reached. It is time to recognize ambient EMF as a novel form of pollution and develop rules at regulatory agencies that designate air as ‘habitat’ so EMF can be regulated like other pollutants. Long-term chronic low-level EMF exposure standards, which do not now exist, should be set accordingly for wildlife, and environmental laws should be strictly enforced — a subject explored in Part 3.
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Hussan, Ghulam, Sajid Khan, Rashid Ahmad, Aamir Farooq e Muhammad Zeeshan Anwar. "Effect of WO3 on the radiation shielding ability of TeO2–TiO2–WO3 glass system". Radiochimica Acta, 30 gennaio 2023. http://dx.doi.org/10.1515/ract-2022-0057.
Abstract (sommario):
Abstract In this study, glass composition based on tungsten oxide (WO3) doped tellurium, titanium glasses: (100 − x − y) TeO2–xTiO2–yWO3: where (x = 5) and (y = 5, 10, 15, 20, 25) coded as TT5W5, TT5W10, TT5W15, TT5W20, and TT5W25 were investigated for shielding properties against ionizing radiation. Gamma radiation shielding parameters such as mass attenuation coefficients (MAC) are calculated through MCNPx code and Phy-X/PSD software in the energy range of 0.015–15 MeV. Obtained MAC values are then used to calculate other gamma radiation shielding parameters such as mean free path (MFP) and effective atomic number (Z eff). Besides this, the exposure buildup factor (EBF) was also calculated by using EXABCal software at different penetration depths (PDs) in the energy range of 0.015–15 MeV. Sample TT5W25, which has a larger WO3 content of 25 mol% shows higher values of MAC and lower values of MFP among all the examined glass samples. Our investigated TeO2–TiO2–WO3 glass samples possess the lowest MFP values in comparison with the different types of concretes and commercially available shielding glasses. In addition, fast neutron shielding characteristics in light of fast neutron removal cross-section have also been computed. Glass sample TT5W25 possesses the higher values of fast neutron removal cross-section as compared to the other glass samples. The results indicate that the adding up of WO3 improves shielding against the fast neutron and gamma radiation.
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Chapagain, Moti, Shruti Athale, Jotam Pasipanodya, David Howe, M. R. K. Alley e Tawanda Gumbo. "1697. Dose-response Studies of the Novel Bacterial Leucyl-tRNA Synthetase Inhibitor, Epetraborole, in the Intracellular Hollow Fiber System Model of Mycobacterium avium complex Lung Disease". Open Forum Infectious Diseases 9, Supplement_2 (1 dicembre 2022). http://dx.doi.org/10.1093/ofid/ofac492.1327.
Abstract (sommario):
Abstract Background Based on meta-analyses the current standard-of-care regimen (SOC) for Mycobacterium avium complex (MAC) lung disease achieves a sustained sputum conversion rate of ∼54% at best. Epetraborole (EBO) is a boron-containing oral inhibitor of bacterial leucyl-tRNA synthetase, an essential enzyme in protein synthesis; EBO demonstrates potent activity against nontuberculous mycobacteria. To identify EBO exposure-effect parameters we used the intracellular hollow fiber system model of intracellular pulmonary MAC (HFS-MAC). Methods EBO was administered once daily at 8 different doses to HFS-MAC replicates for 28 days to achieve a half-life (t½) of 10.4h and the 0-24h area under the concentration-time curves (AUC0-24) that cover the observed AUC values in humans. The SOC combination of clarithromycin (CLR), ethambutol (EMB), and rifabutin (RFB) at human intrapulmonary pharmacokinetic (PK) concentrations was used. The central compartment of each HFS-MAC unit was sampled throughout the 28 days to assess PK parameters as was the peripheral compartment for total bacterial burden and the EBO-resistant bacterial burden. EBO AUC versus total MAC burden was modeled using the inhibitory sigmoid maximal effect (Emax) model. EBO AUC versus EBO-resistant MAC burden was modeled using a quadratic function. Results Measured EBO concentrations demonstrated a t1/2 of 10h. For SOC, the AUC for CLR, EMB, and RFB was 60 mg*h/L (t1/2=6h), 39 mg*h/L (t1/2=8h), and 1.5 mg*h/L (t1/2=45h), respectively, similar to human lung concentrations. Changes in MAC burden over 28 days (Fig. 1) show that highest EBO exposures matched SOC until day 14. The exposure versus effect on each sampling day is shown in Fig. 2. The EBO AUC mediating 50% of Emax (EC50) was an AUC of 22 mg*h/L (95% confidence interval [CI]: 16-70), and the EC80 was an AUC of 47.5 mg*h/L (CI: 34.6-151.2). The relationship between AUC and EBO-resistant subpopulation (Fig. 3) shows that an AUC0-24 of 47.5 mg*h/L, the same as the EC80 for microbial kill, was associated with resistance suppression, as was the addition of SOC to EBO. Figure 1.Changes in bacterial burden over the 28-day dosing period. Bacterial burden on serial samples from all HFS-MAC units and replicates over 28days are shown. The highest epetraborole exposures demonstrated the same effectiveness as the three drug SOC until day 14, after which it failed as resistance emerged. On the other hand adding epetraborole at an AUC of 43.6 mg*h/L to the SOC led to much faster kill (i.e, higher kill slopes) than SOC or the epetraborole monotherapy at the same AUC. Figure 2.Epetraborole exposure versus effect on bacterial burden. Shown are inhibitory sigmoid Emax curves for epetraborole AUC versus log10 CFU/mL on each sampling day, as well as various extents of microbial kill such as stasis (holding burden similar to day 0), 1 log CFU/mL kill and 2 log CFU/mL kill. Beyond day 3, epetraborole killed > 1log CFU/mL, which means it was rapidly bactericidal. Figure 3.Epetraborole exposure versus epetraborole-resistant subpopulation. Drug-resistant burden is shown as log10 CFU/mL. The addition of SOC to EBO totally suppressed emergence of any resistance on all days. Conclusion EBO monotherapy with an AUC0-24 > 16.9 mg*h/L killed > 1.0 log10 CFU/mL of MAC compared to day 0. At the EC80, EBO killed at least 2.0 log10 CFU/mL, thus was highly bactericidal. EBO plus SOC demonstrated resistance suppression. Disclosures Moti Chapagain, MD, PhD, Praedicare Inc.: Stocks/Bonds Shruti Athale, PhD, Praedicare Inc.: Stocks/Bonds Jotam Pasipanodya, MD, PhD, Praedicare Inc.: Employee MRK Alley, PhD, ABBOTT LABS: Stocks/Bonds|ABBVIE: Stocks/Bonds|AN2 Therapeutics: Author on epetraborole patent|AN2 Therapeutics: Salary|AN2 Therapeutics: Ownership Interest|AVANOS MED INC: Stocks/Bonds|NABRIVA THERAPEUTICS PLC: Stocks/Bonds|NOVARTIS AG: Stocks/Bonds Tawanda Gumbo, MD, Hydronium Biopharma: Ownership Interest|Hydronium Biopharma: Stocks/Bonds|Praedicare Africa Pvt Ltd: Board Member|Praedicare Africa Pvt Ltd: Ownership Interest|Praedicare Africa Pvt Ltd: Stocks/Bonds|Praedicare Inc.: Patents|Praedicare Inc.: Ownership Interest|Praedicare Inc.: Stocks/Bonds.
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Mazloum, Taghrid, Shanshan Wang, Maryem Hamdi, Biruk Ashenafi Mulugeta e Joe Wiart. "Artificial Neural Network-Based Uplink Power Prediction From Multi-Floor Indoor Measurement Campaigns in 4G Networks". Frontiers in Public Health 9 (30 novembre 2021). http://dx.doi.org/10.3389/fpubh.2021.777798.
Abstract (sommario):
Paving the path toward the fifth generation (5G) of wireless networks with a huge increase in the number of user equipment has strengthened public concerns on human exposure to radio-frequency electromagnetic fields (RF EMFs). This requires an assessment and monitoring of RF EMF exposure, in an almost continuous way. Particular interest goes to the uplink (UL) exposure, assessed through the transmission power of the mobile phone, due to its close proximity to the human body. However, the UL transmit (TX) power is not provided by the off-the-shelf modem and RF devices. In this context, we first conduct measurement campaigns in a multi-floor indoor environment using a drive test solution to record both downlink (DL) and UL connection parameters for Long Term Evolution (LTE) networks. Several usage services (including WhatsApp voice calls, WhatsApp video calls, and file uploading) are investigated in the measurement campaigns. Then, we propose an artificial neural network (ANN) model to estimate the UL TX power, by exploiting easily available parameters such as the DL connection indicators and the information related to an indoor environment. With those easy-accessed input features, the proposed ANN model is able to obtain an accurate estimation of UL TX power with a mean absolute error (MAE) of 1.487 dB.