Journal articles: 'PfTIM'

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Ravindra, Gudihal, and Padmanabhan Balaram. "Plasmodium falciparum triosephosphate isomerase: New insights into an old enzyme." Pure and Applied Chemistry 77, no. 1 (January 1, 2005): 281–89. http://dx.doi.org/10.1351/pac200577010281.

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Triosephosphate isomerase (TIM), a central enzyme in the glycolytic pathway, has been the subject of extensive structural and mechanistic investigations over the past 30 years. The TIM barrel is the prototype of the (β/α)8 barrel fold, which is one of the most extensively used structural motifs in enzymes. Mechanistic studies on TIM from a variety of sources have emphasized the importance of loop 6 dynamics for enzyme activity. Several conserved residues in TIM have been investigated by extensive site-directed mutagenesis of the enzyme from yeast, chicken, and trypanosoma. The cloning and sequencing of the TIM gene from the malarial parasite Plasmodium falciparum in 1993 revealed the unexpected mutation of a hitherto conserved residue serine (S96) to phenylalanine (F96). Subsequent results from the genome sequencing programs of Plasmodium falciparum, Plasmodium vivax, and Plasmodium yoelii confirmed the presence of the S96F mutation in malarial parasites. The crystal structure of PfTIM and several inhibitor complexes, including a high-resolution (1.1 Å) structure of the PfTIM 2-phosphoglycerate complex, revealed that loop 6 had a propensity to remain open, even in several ligand bound structures. Furthermore, both open and closed forms could be characterized for the same complex. Since glycolysis is the primary source of ATP for the malarial parasite during the intraerythrocytic stage, glycolytic enzymes present themselves as potential targets for inhibitors. Two distinct approaches have been explored. The use of dimer interface peptides, which interfere with assembly, has proved promising. Inactivation of the enzyme by modification of a cysteine (C13) residue, which lies close to the active site residue, lysine (K12) is another potential strategy. The differential reactivity, of the four-cysteine residues, at positions 13, 126, 196, and 217 in each subunit has been established using electrospray ionization mass spectrometry. Studies of single tryptophan mutants (W11F and W168F) of PfTIM provide a probe to study folding, stability, and inhibitor interactions.

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Lee, So-Hyoun, Jong-Hoon Moon, Chang-Mo Jeong, Eun-Bin Bae, Chung-Eun Park, Gye-Rok Jeon, Jin-Ju Lee, Young-Chan Jeon, and Jung-Bo Huh. "The Mechanical Properties and Biometrical Effect of 3D Preformed Titanium Membrane for Guided Bone Regeneration on Alveolar Bone Defect." BioMed Research International 2017 (2017): 1–12. http://dx.doi.org/10.1155/2017/7102123.

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The purpose of this study is to evaluate the effect of three-dimensional preformed titanium membrane (3D-PFTM) to enhance mechanical properties and ability of bone regeneration on the peri-implant bone defect. 3D-PFTMs by new mechanically compressive molding technology and manually shaped- (MS-) PFTMs by hand manipulation were applied in artificial peri-implant bone defect model for static compressive load test and cyclic fatigue load test. In 12 implants installed in the mandibular of three beagle dogs, six 3D-PFTMs, and six collagen membranes (CM) randomly were applied to 2.5 mm peri-implant buccal bone defect with particulate bone graft materials for guided bone regeneration (GBR). The 3D-PFTM group showed about 7.4 times higher mechanical stiffness and 5 times higher fatigue resistance than the MS-PFTM group. The levels of the new bone area (NBA, %), the bone-to-implant contact (BIC, %), distance from the new bone to the old bone (NB-OB, %), and distance from the osseointegration to the old bone (OI-OB, %) were significantly higher in the 3D-PFTM group than the CM group (p<.001). It was verified that the 3D-PFTM increased mechanical properties which were effective in supporting the space maintenance ability and stabilizing the particulate bone grafts, which led to highly efficient bone regeneration.

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Choi, In-Oh, Ji-Su Oh, Sang-Joun Yu, Byung-Ock Kim, and Won-Pyo Lee. "Retrospective Analysis of the Effect of Three-Dimensional Preformed Titanium Mesh on Peri-Implant Non-Contained Horizontal Defects in 100 Consecutive Cases." Applied Sciences 11, no. 2 (January 19, 2021): 872. http://dx.doi.org/10.3390/app11020872.

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This study aimed to clinically and radiographically evaluate the results of guided bone regeneration (GBR) using three-dimensional preformed titanium mesh (3-D-PFTM) for non-contained horizontal defects in 100 consecutive cases. This study involved 100 patients (129 implants) with peri-implant non-contained horizontal defects. The patients were divided into three groups: 3-D-PFTM alone (Group 1), 3-D-PFTM plus cross-linked collagen membrane (Group 2), and 3-D-PFTM plus non-cross-linked collagen membrane (Group 3). Each implant was evaluated radiographically using CBCT at baseline and 6 months postoperatively. At the platform level, the mean horizontal hard tissue gain of all the sites was 3.1 ± 1.3 mm at 6 months postoperatively. The mean rate of mesh exposure was 11.8% in Group 1, 4.2% in Group 2, and 5.0% in Group 3. The mean hard tissue gain rate was 71.0 ± 23.0% in group 1, 84.2 ± 21.5% in group 2, and 84.0 ± 22.9% in group 3. Groups 2 and 3 showed significantly higher hard tissue gain rates than group 1. However, there was no significant difference between the rates in groups 2 and 3. Within the limitations of this study, 3-D-PFTM should be considered as a valuable option for GBR for peri-implant non-contained horizontal defects. The use of an additional resorbable collagen membrane provides additional advantages.

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Bhuyan, Mrinal, Debadatta Saha, and Basanta Kumar Baishya. "An analysis of factors determining the requirement of ventriculoperitoneal shunt surgery in the children suffering from posterior fossa tumour: a single centre retrospective review." International Surgery Journal 7, no. 4 (March 26, 2020): 1025. http://dx.doi.org/10.18203/2349-2902.isj20201013.

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Background: Hydrocephalus is a relatively common occurrence in a children suffering from the posterior fossa tumour (PFTm). However, there is a divided opinion regarding the ventriculoperitoneal shunt (VPS) surgery before the posterior fossa tumour resection in a child. For the better clinical outcome, we should be able to predict which patient will require VPS following the resection of PFTm. Purpose of our retrospective analysis is to analyse various factors that predicts the necessity of VPS following PFTm resection.Methods: A consecutive series of twenty-six patients who underwent PFTm resection without undergoing VPS preoperatively are analysed in our series.Results: In our series, we found that the younger age at presentation, incomplete tumour resection, longer period of artificial ventilatory support, insertion of external ventricular drain (EVD) and its duration during the postoperative period correlate the necessity of VPS following PFTm resection. However, the severity of hydrocephalus prior to tumor surgery, tumour size, anatomical location of the tumour, tumour dissemination, use of Dural grafts during closure and histopathological type do not predict the requirement of the VPS following PFTm.Conclusions: Patients who are younger at diagnosis should be treated with utmost importance. Gross total resection should be the goal. Factors which predict the likelihood of the EVD which parallels the likelihood of postresection hydrocephalus must be prevented for the better clinical outcome.

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Van Voorhis, Wesley C., Kasey L. Rivas, Pravin Bendale, Laxman Nallan, Carolyn Hornéy, Lynn K. Barrett, Kevin D. Bauer, et al. "Efficacy, Pharmacokinetics, and Metabolism of Tetrahydroquinoline Inhibitors of Plasmodium falciparum Protein Farnesyltransferase." Antimicrobial Agents and Chemotherapy 51, no. 10 (July 2, 2007): 3659–71. http://dx.doi.org/10.1128/aac.00246-07.

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ABSTRACT New antimalarials are urgently needed. We have shown that tetrahydroquinoline (THQ) protein farnesyltransferase (PFT) inhibitors (PFTIs) are effective against the Plasmodium falciparum PFT and are effective at killing P. falciparum in vitro. Previously described THQ PFTIs had limitations of poor oral bioavailability and rapid clearance from the circulation of rodents. In this paper, we validate both the Caco-2 cell permeability model for predicting THQ intestinal absorption and the in vitro liver microsome model for predicting THQ clearance in vivo. Incremental improvements in efficacy, oral absorption, and clearance rate were monitored by in vitro tests; and these tests were followed up with in vivo absorption, distribution, metabolism, and excretion studies. One compound, PB-93, achieved cure when it was given orally to P. berghei-infected rats every 8 h for a total of 72 h. However, PB-93 was rapidly cleared, and dosing every 12 h failed to cure the rats. Thus, the in vivo results corroborate the in vitro pharmacodynamics and demonstrate that 72 h of continuous high-level exposure to PFTIs is necessary to kill plasmodia. The metabolism of PB-93 was demonstrated by a novel technique that relied on double labeling with a radiolabel and heavy isotopes combined with radiometric liquid chromatography and mass spectrometry. The major liver microsome metabolite of PB-93 has the PFT Zn-binding N-methyl-imidazole removed; this metabolite is inactive in blocking PFT function. By solving the X-ray crystal structure of PB-93 bound to rat PFT, a model of PB-93 bound to malarial PFT was constructed. This model suggests areas of the THQ PFTIs that can be modified to retain efficacy and protect the Zn-binding N-methyl-imidazole from dealkylation.

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Lee, So-Ra, Tae-Sik Jang, Chang-Su Seo, In-Oh Choi, and Won-Pyo Lee. "Hard Tissue Volume Stability Effect beyond the Bony Envelope of a Three-Dimensional Preformed Titanium Mesh with Two Different Collagen Barrier Membranes on Peri-Implant Dehiscence Defects in the Anterior Maxilla: A Randomized Clinical Trial." Materials 14, no. 19 (September 27, 2021): 5618. http://dx.doi.org/10.3390/ma14195618.

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This single-blinded, randomized, controlled study aimed to clinically and radiographically evaluate hard tissue volume stability beyond the bony envelope using three-dimensional preformed titanium mesh (3D-PFTM) for peri-implant dehiscence defects in the anterior maxilla. A total of 28 patients who wished to undergo implant surgery combined with guided bone regeneration (GBR) after extraction of a single maxillary anterior tooth were randomly assigned to two groups depending on the type of collagen membrane used, additionally with the 3D-PFTM—test (n = 14, cross-linked collagen membrane; CCM) and control (n = 14, non-cross-linked collagen membrane; NCCM) groups. Each implant was evaluated radiographically using CBCT at baseline, immediately after surgery, and at 6 months postoperatively. The relative position and distances from the bony envelope to the outlines of the augmented ridge were further determined immediately after GBR and 6 months after healing. At the platform level, the mean horizontal hard tissue gain (HG) at all the sites was 2.35 ± 0.68 mm at 6 months postoperatively. The mean HG rate was 84.25% ± 14.19% in the CCM group and 82.56% ± 13.04% in the NCCM group, but the difference was not significant between the groups. In all cases, HG was maintained beyond the bony envelope even after 6 months of GBR. This study suggests that 3D-PFTM should be considered a valuable option for GBR for peri-implant dehiscence defects in the anterior maxilla. In addition, 3D-PFTM may confer predictable hard tissue volume stability even after the healing period of hard tissue augmented outside the bony envelope by GBR.

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Skariya, P. D., M. Satheesh, Edwin Raja J. Dhas, and G. Chandrasekar. "Investigation on Microstructural Examination of Flux Bounded TIG Weldments in Post Weld Heat Treated State." Journal of Computational and Theoretical Nanoscience 16, no. 2 (February 1, 2019): 512–15. http://dx.doi.org/10.1166/jctn.2019.7760.

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The structural material identified for this work is 15CDV6 steel belongs to the category of High strength low alloy (HSLA) family. This research is conducted in the area of Powdered flux TIG (PFTIG) and Flux bounded TIG (FBTIG) welding with the assistance of optimum process parameters procured from Grey wolf optimization tool generated in MATLAB software. The optimum nanopowder and flux gap obtained from PFTIG and FBTIG welding are utilized for the fabrication of closed square butt joint. The microstructural characterization of FBTIG weldments is analyzed in Post weld heat treated (PWHT) condition. The microstructural examinations were conducted with the help of optical and scanning electron microscopy (SEM) to evaluate the structures in the weld zone, Heat affected zone and parent material. The presence of coarse grain structure observed in the WZ leads to the lower strength and hardness of the weldment. The presence of tempered martensite in the HAZ induces strength and toughness to the region.

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Wei, Kexi, Guixiu Wen, Yan Zhao, Zhenghuan Lin, Xiaofei Mei, Limei Huang, and Qidan Ling. "Diarylmaleimide fluorophores: intensely emissive low-band-gap guest for single white polymers with highly efficient electroluminescence." Journal of Materials Chemistry C 4, no. 41 (2016): 9804–12. http://dx.doi.org/10.1039/c6tc03348b.

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Intensely emissive diarylmaleimides PM and TM were introduced into the backbone of polyfluorene (PF) to obtain single white polymers, PFPM and PFTM. PFPM showed highly efficient and white electroluminescence for effective energy transfer from the PF host to the maleimide guest.

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Skariya. P. D et al.,, Skariya P. D. et al ,. "Experimental Investigation of Pftig Welding Process on 15CDV6 Steel using Nanopowders." International Journal of Mechanical and Production Engineering Research and Development 8, no. 4 (2018): 237–46. http://dx.doi.org/10.24247/ijmperdaug201826.

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Oliveira, Rafaela Ribeiro de, André Luis Calado Araújo, and Marco Antonio Calazans Duarte. "Estudo do potencial de formação de trihalometanos na lagoa de Extremoz (RN)." Engenharia Sanitaria e Ambiental 25, no. 2 (March 2020): 315–22. http://dx.doi.org/10.1590/s1413-41522020181889.

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RESUMO O potencial de formação de trihalometanos (PFTHM) é uma metodologia utilizada para avaliar a possibilidade de formação de subprodutos da desinfecção (SPD) por cloração durante o processo de tratamento da água. Trihalometanos (THM) são compostos organoclorados e representam a soma de clorofórmio, diclorobromometano, dibromoclorometano e bromofórmio, sendo a principal classe de SPD formados a partir da reação entre o cloro residual livre e a matéria orgânica natural (MON) presente na água bruta de mananciais de superfície. Esta pesquisa teve como objetivo avaliar o PFTHM resultante da aplicação de cloro na água bruta da lagoa de Extremoz, cuja tecnologia de tratamento utilizada é a filtração direta, seguida de desinfecção com cloro. Os resultados obtidos indicaram presença de matéria orgânica natural hidrofílica com predominância de ácidos fúlvicos na água bruta do manancial. A concentração média de TTHM7 (4,22 mg.L-1) revelou que a água do manancial possui forte potencialidade para formação de compostos orgânicos halogenados. O clorofórmio representou cerca de 80% da concentração total de THM nos ensaios realizados. Foram observadas correlações fortes e significativas entre as variáveis dureza (R = 0,90 e p = 0,005) e cor aparente (R = -0,93 e p = 0,002) da água bruta, resultados que indicaram que íons Ca2+ e Mg2+ podem promover a formação de THM, assim como a cor aparente.

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Pannippara, Manzur Ali, Sapna Kesav, Mol Kollakal Naduvil Rag Rekha, Mathew Abraham, Ganapathy Bhat Sarita, and Kothanan Kozhiyil Elyas. "Characterization and Potent Application of Pleurotus floridanus Trypsin Inhibitor (PfTI)." Natural Product Sciences 26, no. 3 (September 30, 2020): 207–13. http://dx.doi.org/10.20307/nps.2020.26.3.207.

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LIU, XUEWU, YUXIAO HUANG, JIAO LIANG, JUN WANG, YAN SHEN, YINGHUI LI, and YA ZHAO. "Characterization of the malaria parasite protein PfTip, a novel invasion-related protein." Molecular Medicine Reports 13, no. 4 (February 18, 2016): 3303–10. http://dx.doi.org/10.3892/mmr.2016.4910.

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Chen, Guan-Yu, Yung-Fung Chiu, Jing-Hua Lin, Chin-Chu Liu, Yi-Wei Chang, and Cheng-Jia Lien. "Combining Tsunami Hazard and Vulnerability on the Assessment of Tsunami Inundation Probability in Taiwan." Journal of Earthquake and Tsunami 08, no. 03 (August 20, 2014): 1440003. http://dx.doi.org/10.1142/s179343111440003x.

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As earthquake and tsunami are closely related, the probability of tsunami hazard had been done by extending the approach used in earthquakes. However, the hazard of tsunami depends also on the vulnerability of neighboring structures and hence its hazard and vulnerability should not be assessed separately. The distribution of tsunami height varies so significantly that the traditional definition parallel to that in seismic risk should be modified. Besides, previous studies on the probability of tsunami focused on the occurrence possibility of tsunami hazard in a fixed period of time, but this information is not applicable for a specific tsunami incidence. For the above-mentioned problems, a new algorithm that comprises two components is proposed in the present study. The first component, the Probabilistic Forecast of Tsunami Inundation (PFTI), is the conditional inundation probability once a tsunami of a specific height occurs, or an earthquake is detected at some specific location with a specific magnitude. PFTI comprises the assessments of both tsunami hazard and vulnerability, and can be directly applied to a specific tsunami incidence. The second component treats the Tsunamigenic Earthquake Number (TEN) modified from previous studies on tsunami hazard. These two components are combined to give the inundation possibility in a fixed period of time dubbed Earthquake-induced Tsunami Inundation Probability (ETIP) and the result can be used in urban planning or disaster mitigation guidelines. Application of this methodology to the coast of Taiwan is also discussed.

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Bazzoli, Caroline, Sylvie Retout, and France Mentré. "Design evaluation and optimisation in multiple response nonlinear mixed effect models: PFIM 3.0." Computer Methods and Programs in Biomedicine 98, no. 1 (April 2010): 55–65. http://dx.doi.org/10.1016/j.cmpb.2009.09.012.

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Agbekodo, K., B. Legube, P. Côté, and M. M. M. Bourbigot. "Performance de la nanofiltration pour l'élimination de la matière organique naturelle: essais sur l'usine de Méry/Oise." Revue des sciences de l'eau 7, no. 2 (April 12, 2005): 183–200. http://dx.doi.org/10.7202/705196ar.

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L'intérêt croissant que les traiteurs d'eaux portent à l'élimination de la matière organique naturelle (MON) a abouti au développement de nouvelles technologies de traitement. Dans ce but, un prototype de nanofiltration à l'échelle industrielle (2 x 1400 m 3 j-¹) est installé à l'usine de Méry sur Oise depuis juillet 1992. Utilisé en traitement de finition après clarification et filtration sur sable, il alimente depuis février 1993 un réseau test de la commune d'Auvers sur Oise (6 000 hbts) en région parisienne. L'objectif de cette publication est de présenter quelques uns des résultats de caractérisation de la MON obtenus pendant 9 mois d'expérimentation (octobre 1992 à juillet 1993), et en particulier ceux concernant les rendements d'élimination de la matière organique naturelle et par voie de conséquence de la demande en chlore. Ces rendements sont généralement supérieurs à 90 % en termes de COD,CODB et d'absorbance UV à 254 et 270 nm éliminés. L'analyse des potentiels de réactivité avec le chlore (taux de chloration: 2,5 mg Cl2/mg C, temps de réaction: 72 heures, pH = 7,5, 20 °C) montre que le perméat est peu consommateur de chlore (demande en chlore < 0,2 mg l-¹ Cl2) et peu précurseur de chloroforme et de trihalométhanes (PFCHC13 < 3 µg l-¹, PFTHM < 11 µg l-¹). Les rendements d'élimination des PFTHM et PFTOX sont généralement supérieurs à 90 %. L'analyse spécifique des constituants majoritaires du perméat montre que les acides aminés totaux (hydrolyse acide puis dérivation à l'OPA/HPLC) constituent une proportion importante du COD (25 à 60 % selon les saisons). Ces composés représentent la quasi totalité de la demande en chlore du perméat si l'on se réfère aux données bibliographiques. Compte tenu de ces résultats, la nanofiltration apparaît comme un excellent procédé de traitement de finition des eaux à potabiliser. En effet, bien qu'elle constitue une barrière de sécurité contre les germes pathogènes, la très faible charge organique du perméat obtenu par nanofiltration (COD~0,15 à 0,3 mg l-¹ C, CODB<0,1 mg l-¹ C) rend plus aisée la maîtrise du résiduel de chlore (lorsqu'une chloration est nécessaire pour maintenir la qualité de l'eau dans les réseaux) et constitue une limitation importante de la formation des sous-produits de chloration.

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Dumont, Cyrielle, Giulia Lestini, Hervé Le Nagard, France Mentré, Emmanuelle Comets, Thu Thuy Nguyen, and for the PFIM group. "PFIM 4.0, an extended R program for design evaluation and optimization in nonlinear mixed-effect models." Computer Methods and Programs in Biomedicine 156 (March 2018): 217–29. http://dx.doi.org/10.1016/j.cmpb.2018.01.008.

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Murray, Colleen, and John T. Christeller. "Purification of a Trypsin Inhibitor (PFTI) from Pumpkin Fruit Phloem Exudate and Isolation of Putative Trypsin and Chymotrypsin Inhibitor cDNA Clones." Biological Chemistry Hoppe-Seyler 376, no. 5 (January 1995): 281–88. http://dx.doi.org/10.1515/bchm3.1995.376.5.281.

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Maher, Ali, Masaki Kitazume, Masoud Janbaz, Robert Miskewitz, Scott Douglas, and David Yang. "Utilization of pneumatic flow tube mixing technique (PFTM) for processing and stabilization of contaminated soft sediments in the NY/NJ Harbor." Marine Georesources & Geotechnology 36, no. 3 (December 21, 2017): 271–79. http://dx.doi.org/10.1080/1064119x.2016.1257668.

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Drevin, Guillaume, Marie Briet, Caroline Bazzoli, Emmanuel Gyan, Aline Schmidt, Hervé Dombret, Corentin Orvain, et al. "Daunorubicin and Its Active Metabolite Pharmacokinetic Profiles in Acute Myeloid Leukaemia Patients: A Pharmacokinetic Ancillary Study of the BIG-1 Trial." Pharmaceutics 14, no. 4 (April 5, 2022): 792. http://dx.doi.org/10.3390/pharmaceutics14040792.

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Daunorubicin pharmacokinetics (PK) are characterised by an important inter-individual variability, which raises questions about the optimal dose regimen in patients with acute myeloid leukaemia. The aim of the study is to assess the joint daunorubicin/daunorubicinol PK profile and to define an optimal population PK study design. Fourteen patients were enrolled in the PK ancillary study of the BIG-1 trial and 6–8 samples were taken up to 24 h after administration of the first dose of daunorubicin (90 mg/m2/day). Daunorubicin and daunorubicinol quantifications were assessed using a validated liquid chromatography technique coupled with a fluorescence detector method. Data were analysed using a non-compartmental approach and non-linear mixed effects modelling. Optimal sampling strategy was proposed using the R function PFIM. The median daunorubicin and daunorubicinol AUC0-tlast were 577 ng/mL·hr (Range: 375–1167) and 2200 ng/mL·hr (range: 933–4683), respectively. The median metabolic ratio was 0.32 (range: 0.1–0.44). Daunorubicin PK was best described by a three-compartment parent, two-compartment metabolite model, with a double first-order transformation of daunorubicin to metabolite. Body surface area and plasma creatinine had a significant impact on the daunorubicin and daunorubicinol PK. A practical optimal population design has been derived from this model with five sampling times per subject (0.5, 0.75, 2, 9, 24 h) and this can be used for a future population PK study.

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Oyaga-Iriarte, Esther, Asier Insausti, Lorea Bueno, Onintza Sayar, and Azucena Aldaz. "Mining Small Routine Clinical Data: A Population Pharmacokinetic Model and Optimal Sampling Times of Capecitabine and its Metabolites." Journal of Pharmacy & Pharmaceutical Sciences 22 (April 9, 2019): 112–21. http://dx.doi.org/10.18433/jpps30392.

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Purpose: The present study was performed to demonstrate that small amounts of routine clinical data allow to generate valuable knowledge. Concretely, the aims of this research were to build a joint population pharmacokinetic model for capecitabine and three of its metabolites (5-DFUR, 5-FU and 5-FUH2) and to determine optimal sampling times for therapeutic drug monitoring. Methods: We used data of 7 treatment cycles of capecitabine in patients with metastatic colorectal cancer. The population pharmacokinetic model was built as a multicompartmental model using NONMEM and was internally validated by visual predictive check. Optimal sampling times were estimated using PFIM 4.0 following D-optimality criterion. Results: The final model was a multicompartmental model which represented the sequential transformations from capecitabine to its metabolites 5-DFUR, 5-FU and 5-FUH2 and was correctly validated. The optimal sampling times were 0.546, 0.892, 1.562, 4.736 and 8 hours after the administration of the drug. For its correct implementation in clinical practice, the values were rounded to 0.5, 1, 1.5, 5 and 8 hours after the administration of the drug. Conclusions: Capecitabine, 5-DFUR, 5-FU and 5-FUH2 can be correctly described by the joint multicompartmental model presented in this work. The aforementioned times are optimal to maximize the information of samples. Useful knowledge can be obtained for clinical practice from small databases.

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Petit, Caroline, Vincent Jullien, Adeline Samson, Jérémie Guedj, Jean-René Kiechel, Sarah Zohar, and Emmanuelle Comets. "Designing a Pediatric Study for an Antimalarial Drug by Using Information from Adults." Antimicrobial Agents and Chemotherapy 60, no. 3 (December 28, 2015): 1481–91. http://dx.doi.org/10.1128/aac.01125-15.

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The objectives of this study were to design a pharmacokinetic (PK) study by using information about adults and evaluate the robustness of the recommended design through a case study of mefloquine. PK data about adults and children were available from two different randomized studies of the treatment of malaria with the same artesunate-mefloquine combination regimen. A recommended design for pediatric studies of mefloquine was optimized on the basis of an extrapolated model built from adult data through the following approach. (i) An adult PK model was built, and parameters were estimated by using the stochastic approximation expectation-maximization algorithm. (ii) Pediatric PK parameters were then obtained by adding allometry and maturation to the adult model. (iii) A D-optimal design for children was obtained with PFIM by assuming the extrapolated design. Finally, the robustness of the recommended design was evaluated in terms of the relative bias and relative standard errors (RSE) of the parameters in a simulation study with four different models and was compared to the empirical design used for the pediatric study. Combining PK modeling, extrapolation, and design optimization led to a design for children with five sampling times. PK parameters were well estimated by this design with few RSE. Although the extrapolated model did not predict the observed mefloquine concentrations in children very accurately, it allowed precise and unbiased estimates across various model assumptions, contrary to the empirical design. Using information from adult studies combined with allometry and maturation can help provide robust designs for pediatric studies.

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Long-Boyle, Janel R., Shirley Yan, Christopher C. Dvorak, Biljana N. Horn, Morton Jerome Cowan, Liusheng Huang, Nancy Sambol, Lisa Musick, and Francesca Aweeka. "An Interim Evaluation of Systemic F-Ara-a Exposure in Pediatric Allogeneic Hematopoietic Cell Transplant (alloHCT) Recipients Using An Optimal Sampling Design." Blood 118, no. 21 (November 18, 2011): 1962. http://dx.doi.org/10.1182/blood.v118.21.1962.1962.

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Abstract Abstract 1962 Background Fludarabine is a purine analogue used in the preparative regimens of pediatric alloHCT to enhance stem cell engraftment. Administered intravenously as a prodrug, fludarabine (f-ara-AMP) undergoes rapid dephosphorylation in the plasma to the systemically circulating compound, f-ara-a. Despite widespread use, there are no published pharmacokinetic-pharmacodynamic (PK-PD) studies of fludarabine in children undergoing alloHCT. Using an optimal sampling strategy (OSS), we designed a prospective study to evaluate the PK-PD of fludarabine in pediatric alloHCT recipients. We report the year-1 interim PK analysis of this 3-year exposure-response study. Methods Utilizing prior f-ara-a PK data available in adults and D-optimal sampling methods (PFIM software), we designed an OSS for f-ara-a in children. Based on the OSS, the relative standard errors (RSE), representing the precision of estimated PK parameters, were predicted to be less than 20% in a total of 45 children. An interim analysis was planned after year 1 to ensure the sample collection times selected by the OSS were sufficiently informative. Patients were eligible to participate in PK sampling if they were between 0 to 17 years of age, met protocol specific criteria for alloHCT, and would be receiving fludarabine as part of their preparative regimen. All patients underwent PK sampling with dose 1 of fludarabine. Fludarabine was infused per protocol over 30–60 minutes and 1 mL of whole blood was obtained at 2, 4, 8, and 24 h after the start of infusion. PK sampling was repeated following a subsequent dose of fludarabine (dose 2, 3, 4 or 5) at 2 and 24 h. Plasma samples were analyzed by LC-tandem MS and the assay was linear in the range of 5–500 ng/mL. PK model development using f-ara-a concentration-time data was carried out using standard population PK methodologies (NONMEM 7.2 software). Further development of a 2-compartment open model was based on exploratory analysis, diagnostic plots and changes in objective function value (OFV). The addition of allometric scaling, with weight built into the base model scaled to a reference patient having the median weight of the population, resulted in a significant drop in the OFV. No other covariates were tested based on exploratory analysis and plots. The model was parameterized in terms of clearance (CL), volume of distribution-central compartment (Vc), volume of distribution-peripheral compartment (Vp), and inter-compartmental clearance (Q). Residual unexplained variability was modeled as being proportional to the predicted concentrations. Area-under-the-curve (AUC) of f-ara-a was derived from the empirical Bayes estimates of individual CL. Results A total of 94 quantifiable concentrations from 16 subjects (10 male, 6 female) were available for interim PK modeling. Most patients received fludarabine 30–40mg/m2 daily over 3 to 5 days (n=13). In the 3 smallest children (<10kg), fludarabine was dosed at 1.33mg/kg/day for 3 to 4 days. Median age and weight of subjects was 6.5 years (range, 0.3–17) and 23.4kg (6.8-82.3), respectively. Markers for renal function were within normal age limits for all subjects. A 2-compartment model with linear elimination well described the PK of f-ara-a. The population PK estimates for CL, Vc, Vp, Q, and their RSE (%) were 9.0 (6.3%), 30 (8.9%), 34 (6.4%), and 7.7 (11%), respectively. The final model of this interim analysis estimated f-ara-a CL (L/h) = 9.0 * (WT/23.4)0.67. This model predicts f-ara-a CL (%CV) to be lower for children < 10kg (n=3), 3.8 L/h (11.3%) compared to those >10kg, 12.4 L/h (42%). Correspondingly, dose-normalized AUC was predicted to be approximately 2.8 times higher in patients < 10kg. Between-patient variability of CL was estimated to be 23% and the residual variability of concentrations 25%. Conclusion The optimal sampling strategy based on adult prior data allows for accurate estimation of f-ara-a population PK parameters in our study of 16 pediatric alloHCT recipients. These interim results suggest body weight may be used to predict f-ara-a clearance, as well as suggest the need for close evaluation of weight-based dosing to prevent over-exposure in very small children. Over the next 2 years we will continue to enroll children in this PK-PD study to confirm the interim PK results and identify exposure-response relationships to inform optimal dosing of fludarabine in pediatric alloHCT. Disclosures: Off Label Use: Fludarabine (Fludara) has no offical FDA indication for use in children.

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Ford, Thierry, Adriana Rizzo, Ella Hendriks, Tine Frøysaker, and Francesco Caruso. "A non-invasive screening study of varnishes applied to three paintings by Edvard Munch using portable diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS)." Heritage Science 7, no. 1 (October 22, 2019). http://dx.doi.org/10.1186/s40494-019-0327-1.

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Abstract The availability and popularity of portable non-invasive instrumentation for the study of paintings has increased due to a shift away from using micro-invasive techniques. Fourier transform infrared spectroscopy (FTIR) is a successful and established technique for the characterisation of organic materials in varnish coatings and paint films. In addition, portable FTIR (pFTIR) spectrometers allow for non-invasive in situ analyses. This overcomes the disadvantages associated with micro-sampling and reproducibility issues encountered in analysis at a specific spot, as pFTIR enables examination of the whole painting. However, the practical applications and capabilities of pFTIR as a suitable screening method for the chemical characterization of varnish coatings in painting collections require systematic evaluation. This study involves a selection of three paintings from the collection of 57 works by Edvard Munch belonging to The National Museum of Art in Norway. Its focus is the identification of the non-original varnish types that were applied by the museum. Between 1909 and 1993, the Museum was embroiled in a varnish controversy due to their application of, first natural and then synthetic, varnish coatings to 48 of these Munch paintings. A series of public debates arose about the Museum’s varnishing practice, which ran counter to the artist’s usual custom of leaving paint surfaces unvarnished (or occasional locally varnished). The three paintings were screened using a pFTIR spectrometer. Different regions of the varnished and unvarnished painted surfaces were analysed with Portable Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS). These paintings date from 1887 to 1891 and are documented as having been treated at the Museum with one of the following types of natural or low-molecular-weight synthetic varnish coatings: dammar, mastic, polycyclohexanone (Laropal K 80 from BASF) and reduced or hydrogenated cyclohexanone-co-methyl-cyclohexanone (MS2A from Howards of Ilford). Surface microscopy and multispectral imaging of the varnished surfaces initially assisted the mapping and choice of areas relevant for the portable DRIFTS measurements. Portable X-Ray fluorescence and surface gloss readings were also made at the pFTIR spot locations to complement the results. Using known dry varnish samples, pFTIR reference spectra were obtained and a DRIFT spectral library was also created from known historic batches of varnishes used by the museum. These were then compared with the in situ pFTIR surface readings taken from the paintings together with additional spectra acquired from a selected number of micro-samples from the same spot locations. The preliminary measurements provided an insight into the capabilities, limitations and practical aspects of using portable DRIFTS for the identification of varnish coatings present in this specific selection of Munch paintings.

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Armstrong, Matthew K., Virginia R. Nuckols, Colin J. Gimblet, Seth W. Holwerda, Lyndsey E. DuBose, Rachel E. Luehrs, Abbi D. Lane, Julio A. Chirinos, Michelle W. Voss, and Gary L. Pierce. "Relation of forward and backward traveling pressure waves with subclinical carotid artery wall remodeling and central pulse pressure." Journal of Applied Physiology, August 31, 2023. http://dx.doi.org/10.1152/japplphysiol.00286.2023.

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Central pulse pressure (PP) is the sum of a forward and backward traveling pressure waves which have been associated with cardiovascular disease (CVD) risk. However, previous studies have reported differential findings regarding importance of the forward versus the backward wave for CVD risk. Therefore, we sought to determine the degree to which the forward and backward pressure waves are associated with subclinical carotid artery wall remodeling and central PP in healthy adults. Using applanation tonometry, carotid pressure waveforms were acquired in 308 healthy individuals (aged 45±17 years, range 19-80 years, 61% women), from which the time integral of the forward (PfTI) and backward (PbTI) pressure waves were derived via pressure-only wave separation analysis. Common carotid artery intima-media thickness (cIMT), a biomarker of subclinical CVD risk, was derived via B-mode ultrasonography measured ~2 cm from the carotid bulb. Both PfTI (r=0.31, P<0.001) and PbTI (r=0.40, P<0.001) were correlated with cIMT. However, further analysis revealed that PbTI mediated the relation between PfTI and cIMT (proportion mediated=156%, P<0.001). The association between PbTI and cIMT remained after adjusting for age, sex, body mass index, blood glucose, low-density lipoprotein cholesterol, heart rate, brachial systolic pressure, and aortic stiffness (B=0.02, 95% confidence interval=0.01, 2.77, P<0.001). Both PfTI (r=-0.58, P<0.001) and PbTI (r=-0.50, P<0.001) were correlated with central PP, however, PfTI fully mediated the association between PbTI and central PP (proportion mediated=124%, P<0.001). Although PfTI is correlated with higher central PP, it is PbTI that is directly associated with carotid artery wall remodeling.

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Vasilev, Viktor Yakovlevich. "VORTEX RATIONAL (ENERGY-SAVING) HEAT EXCHANGE ENHANCEMENT IN NON-SIRCULAR DUCTS OF SHIP HEAT EXCHANGERS." Vestnik of Astrakhan State Technical University. Series: Marine engineering and technologies, November 25, 2018, 75–88. http://dx.doi.org/10.24143/2073-1574-2018-4-75-88.

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High demands placed to the quality of ship heat exchangers are determined by their outer dimensions and weight, power consumption for heat-transfer agents circulating, size of heat loading, operational availability, processability and manufacturing profitability. Lamellar-ribbed heat exchangers most successfully meet the listed requirements. Two methods of generating vortices (in the case of flow around poorly streamlined bodies and at divergent-convergent segments) in the wall layer of currents in rectangular ducts are realized in 10 plate-fin interrupted (PFTsm) heat transfer surfaces and in 31 tub-plate (TPsm) heat transfer surfaces (HTS) with cross ridges and grooves in order to determine the regularities of rational enhancement of convective heat transfer. The results of experimental studies of the thermo-aerodynamic characteristics of 19 groups from a limited number (4-6) of PFTsm or TP sm heat transfer surfaces and one of 5 tested smooth channeled HTS ( L / d = 19,43 - PFTsm and L / d = 10,50-15,62 - TP sm ) confirmed the realization of rational enhancement of convective heat transfer ( RECHT ) processes and the high level of their estimates (Nu/Nusm)¢max for the value of the complex (Nu/Nusm)Re=idem/(ζ/ζsm)Re=idem = 1, showed the contribution of changed values of geometric parameters δ/ d (0,0580-0,1138), l / d (0,65-3,24) of PFTint and d */ d (0,748-0,953), l / d (0,183-2,003) of TP int HTS in the value of RECHT estimates. There has been proposed and realized (for the studied HTS groups) a technique for determining the ranges of changing values of geometric and regime parameters that proves the realization of the RECHT process, which simplifies the search for rational solutions in the design of heat exchangers. Special conditions of the preparation for the experiments made it possible to exclude the negative effect of side factors on the results.

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Pinto, Hêider Aurélio, and Soraya Vargas Côrtes. "Um modelo teórico-metodológico para análises de políticas com longas trajetórias e ação de atores em prol da mudança e da estabilidade." Interface - Comunicação, Saúde, Educação 27 (2023). http://dx.doi.org/10.1590/interface.220186.

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Políticas públicas, frequentemente, estão associadas a legados históricos constituídos em processos políticos nos quais atores agem em prol da mudança ou da estabilidade institucional. Este artigo apresenta uma proposta teórico-metodológica que usa o process tracing na identificação dos processos mais relevantes para o estudo da trajetória de políticas, por intermédio das lentes teóricas oferecidas pelos estudos sobre processo político e Teoria da Mudança Institucional Gradual. Essa abordagem teórico-metodológica possibilitou a identificação e a compreensão da influência de diferentes atores, de arranjos institucionais e mudanças na política para a força de trabalho médica (PFTM) da década de 1960 a 2010, bem como propiciou que se apreendesse na análise a importância da ação de atores que dirigiram o Ministério da Saúde, a partir de 2003, interessados em direcionar a PFTM às necessidades do Sistema Único de Saúde (SUS).

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Mohammadifar, Aliakbar, Hamid Gholami, and Shahram Golzari. "Assessment of the uncertainty and interpretability of deep learning models for mapping soil salinity using DeepQuantreg and game theory." Scientific Reports 12, no. 1 (September 7, 2022). http://dx.doi.org/10.1038/s41598-022-19357-4.

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AbstractThis research introduces a new combined modelling approach for mapping soil salinity in the Minab plain in southern Iran. This study assessed the uncertainty (with 95% confidence limits) and interpretability of two deep learning (DL) models (deep boltzmann machine—DBM) and a one dimensional convolutional neural networks (1DCNN)—long short-term memory (LSTM) hybrid model (1DCNN-LSTM) for mapping soil salinity by applying DeepQuantreg and game theory (Shapely Additive exPlanations (SHAP) and permutation feature importance measure (PFIM)), respectively. Based on stepwise forward regression (SFR)—a technique for controlling factor selection, 18 of 47 potential controls were selected as effective factors. Inventory maps of soil salinity were generated based on 476 surface soil samples collected for measuring electrical conductivity (ECe). Based on Taylor diagrams, both DL models performed well (RMSE < 20%), but the 1DCNN-LSTM hybrid model performed slightly better than the DBM model. The uncertainty range associated with the ECe values predicted by both models estimated using DeepQuantilreg were similar (0–25 dS/m for the 1DCNN-LSTM hybrid model and 2–27 dS/m for DBM model). Based on the SFR and PFIM (permutation feature importance measure)—a measure in game theory, four controls (evaporation, sand content, precipitation and vertical distance to channel) were selected as the most important factors for soil salinity in the study area. The results of SHAP (Shapely Additive exPlanations)—the second measure used in game theory—suggested that five factors (evaporation, vertical distance to channel, sand content, cation exchange capacity (CEC) and digital elevation model (DEM)) have the strongest impact on model outputs. Overall, the methodology used in this study is recommend for applications in other regions for mapping environmental problems.

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Agbaba, Jasmina, Aleksandra Tubic, Jelena Molnar, Malcom Watson, Dejan Krcmar, and Bozo Dalmacija. "UTICAJ PREDOZONIZACIJE NA UKLANJANJE PREKURSORA TRIHALOMETANA KOAGULACIJOM." GLASNIK HEMIČARA, TEHNOLOGA I EKOLOGA REPUBLIKE SRPSKE 5, no. 10 (December 15, 2014). http://dx.doi.org/10.7251/ghte1410043a.

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Uticaj predozonizacije na uklanjanje prekursora trihalometana (THM) koagulacijom ispitivan je na podzemnoj vodi sa visokim sadržajem prirodnih organskih materija (5,28±0,65 mg/L DOC; 0,131±0,002 cm-1 UV254) i potencijalom formiranja THM (275±39 µg/ L PFTHM). Jar test je sproveden primenom koagulanata PACl (5-30 mg Al/L) i FeCl3 (100-200 mg/L). PACl se pri svim ispitivanim dozama pokazao kao efikasniji koagulant u pogledu smanjenja sadržaja DOC, u odnosu na FeCl3 (uklonjeno je 9-48% DOC i 9-19% DOC, redom). Najbolji efekti postignuti su pri dozi od 15 mg Al/L PACl i 150 mg/L FeCl3, te je pri ovim dozama dalje ispitivan efekat predozonizacije (0,25-0,8 mg O3/mg DOC) na uklanjanje prekursora THM. Utvrđeno je da koagulacija sa predozonizacijom ima pozitivan uticaj na uklanjanje prekursora THM. Primenom 0,8 mg O3/mg DOC povećava se efikasnost uklanjanja prekursora THM koagulacijom sa PACl (sa 34% na 55%) i FeCl3 (sa 23% na 85%).

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Journal articles on the topic 'PfTIM'

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