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Yuan, Pengfei, Changshuang Fu, Yi Yang, Aipire Adila, Fangfang Zhou, Xianxian Wei, Weilan Wang, et al. "Cistanche tubulosa Phenylethanoid Glycosides Induce Apoptosis of Hepatocellular Carcinoma Cells by Mitochondria-Dependent and MAPK Pathways and Enhance Antitumor Effect through Combination with Cisplatin." Integrative Cancer Therapies 20 (January 2021): 153473542110130. http://dx.doi.org/10.1177/15347354211013085.
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Cistanche tubulosa is a type of Chinese herbal medicine and exerts various biological functions. Previous studies have been demonstrated that Cistanche tubulosa phenylethanoid glycosides (CTPG) exhibit antitumor effects on a variety of tumor cells. However, the antitumor effects of CTPG on HepG2 and BEL-7404 hepatocellular carcinoma (HCC) cells are still elusive. Our study showed that CTPG significantly inhibited the growth of HepG2 and BEL-7404 cells through the induction of cell cycle arrest and apoptosis, which was associated with the activation of MAPK pathways characterized by the up-regulated phosphorylation of p38, JNK, and ERK1/2 and mitochondria-dependent pathway characterized by the reduction of mitochondrial membrane potential. The release of cytochrome c and the cleavage of caspase-3, -7, -9, and PARP were subsequently increased by CTPG treatment. Moreover, CTPG significantly suppressed the migration of HepG2 through reducing the levels of matrix metalloproteinase-2 and vascular endothelial growth factor. Interestingly, CTPG not only enhanced the proliferation of splenocytes but also reduced the apoptosis of splenocytes induced by cisplatin. In H22 tumor mouse model, CTPG combined with cisplatin further inhibited the growth of H22 cells and reduced the side effects of cisplatin. Taken together, CTPG inhibited the growth of HCC through direct antitumor effect and indirect immunoenhancement effect, and improved the antitumor efficacy of cisplatin.
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Horsfield, Mark A., Simon A. Clark, and Timothy J. Norwood. "Estimation of the Characteristic Length Scales forB0Variation Using the OE-CTPG Pulse Sequence." Journal of Magnetic Resonance, Series A 122, no. 2 (October 1996): 222–29. http://dx.doi.org/10.1006/jmra.1996.0198.
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López, Marcela, Laudy-Viviana Quitian, Martha-Nancy Calderón, and Carlos-Y. Soto. "The P-type ATPase CtpG preferentially transports Cd2+ across the Mycobacterium tuberculosis plasma membrane." Archives of Microbiology 200, no. 3 (December 2, 2017): 483–92. http://dx.doi.org/10.1007/s00203-017-1465-z.
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Wu, Hong, Junichi Kato, Akio Kuroda, Tsukasa Ikeda, Noboru Takiguchi, and Hisao Ohtake. "Identification and Characterization of Two Chemotactic Transducers for Inorganic Phosphate in Pseudomonas aeruginosa." Journal of Bacteriology 182, no. 12 (June 15, 2000): 3400–3404. http://dx.doi.org/10.1128/jb.182.12.3400-3404.2000.
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ABSTRACT Two chemotactic transducers for inorganic phosphate (Pi), designated CtpH and CtpL, have been identified inPseudomonas aeruginosa. The corresponding genes (ctpH and ctpL) were inactivated by inserting kanamycin and tetracycline resistance gene cassettes into the wild-type genes in the P. aeruginosa PAO1 genome. Computer-assisted capillary assays showed that the ctpH single mutant failed to exhibit Pi taxis when the concentration of Pi in the capillary was higher than 5 mM. Conversely, thectpL single mutant could not respond to Pi at the concentration of 0.01 mM. The ctpH ctpL double mutant was defective in Pi taxis at any concentration ranging from 0.01 to 10 mM. To investigate regulation of Pi taxis, thectpH and ctpL genes were also disrupted individually in the P. aeruginosa phoU and phoBsingle mutants. The ctpH phoU and ctpH phoBdouble mutants were defective in Pi taxis, regardless of whether the cells were starved for Pi. The ctpL phoU double mutant was constitutive for Pi taxis, whereas the ctpL phoB double mutant was induced by Pi limitation for Pi taxis. The region upstream of ctpL, but not ctpH, contained a putativepho box sequence. Expression ofctpL::lacZ was induced by Pi limitation in PAO1, while it was constitutive in thephoU mutant. In contrast, the phoB mutant showed only background levels ofctpL::lacZ expression. These results showed that ctpL is involved in the pho regulon genes in P. aeruginosa. The ctpH phoU mutant, which failed to exhibit Pi taxis, was constitutive forctpL::lacZ expression, suggesting that the Pi detection by CtpL requires PhoU. Like PAO1, thephoB and phoU single mutants were constitutive for expression of ctpH::lacZ. Thus, the evidence that the ctpL phoU mutant, but not thectpL phoB mutant and PAO1, was constitutive for Pi taxis raised the possibility that PhoU exerts a negative control on Pi detection by CtpH at the posttranscriptional level.
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Lunn, Faylene A., Travis J. MacLeod, and Stephen L. Bearne. "Mutational analysis of conserved glycine residues 142, 143 and 146 reveals Gly142 is critical for tetramerization of CTP synthase from Escherichia coli." Biochemical Journal 412, no. 1 (April 25, 2008): 113–21. http://dx.doi.org/10.1042/bj20071163.
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CTPS (cytidine 5′-triphosphate synthase) catalyses the ATP-dependent formation of CTP from UTP using either ammonia or L-glutamine as the nitrogen source. Binding of the substrates ATP and UTP, or the product CTP, promotes oligomerization of CTPS from inactive dimers to active tetramers. In the present study, site-directed mutagenesis was used to replace the fully conserved glycine residues 142 and 143 within the UTP-binding site and 146 within the CTP-binding site of Escherchia coli CTPS. CD spectral analyses of wild-type CTPS and the glycine mutants showed a slight reduction of ∼15% in α-helical content for G142A and G143A relative to G146A and wild-type CTPS, suggesting some local alterations in structure. Relative to wild-type CTPS, the values of kcat/Km for ammonia-dependent and glutamine-dependent CTP formation catalysed by G143A were reduced 22- and 16-fold respectively, whereas the corresponding values for G146A were reduced only 1.4- and 1.8-fold respectively. The glutaminase activity (kcat) of G146A was similar to that exhibited by the wild-type enzyme, whereas that of G143A was reduced 7.5-fold. G146A exhibited substrate inhibition at high concentrations of ammonia and a partial uncoupling of glutamine hydrolysis from CTP production. Although the apparent affinity (1/[S]0.5) of G143A and G146A for UTP was reduced ∼4-fold, G146A exhibited increased co-operativity with respect to UTP. Thus mutations in the CTP-binding site can affect UTP-dependent activity. Surprisingly, G142A was inactive with both ammonia and glutamine as substrates. Gel-filtration HPLC experiments revealed that both G143A and G146A were able to form active tetramers in the presence of ATP and UTP; however, nucleotide-dependent tetramerization of G142A was significantly impaired. Our observations highlight the sensitivity of the structure of CTPS to mutations in the UTP- and CTP-binding sites, with Gly142 being critical for nucleotide-dependent oligomerization of CTPS to active tetramers. This ‘structural sensitivity’ may limit the number and/or types of mutations that could be selected for during the development of resistance to cytotoxic pyrimidine nucleotide analogues.
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Yin, Bangsheng, Qilong Min, Emily Morgan, Yuekui Yang, Alexander Marshak, and Anthony B. Davis. "Cloud-top pressure retrieval with DSCOVR EPIC oxygen A- and B-band observations." Atmospheric Measurement Techniques 13, no. 10 (October 6, 2020): 5259–75. http://dx.doi.org/10.5194/amt-13-5259-2020.
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Abstract. An analytic transfer inverse model for Earth Polychromatic Imaging Camera (EPIC) observations is proposed to retrieve the cloud-top pressure (CTP) with the consideration of in-cloud photon penetration. In this model, an analytic equation was developed to represent the reflection at the top of the atmosphere from above cloud, in cloud, and below cloud. The coefficients of this analytic equation can be derived from a series of EPIC simulations under different atmospheric conditions using a nonlinear regression algorithm. With estimated cloud pressure thickness, the CTP can be retrieved from EPIC observation data by solving the analytic equation. To simulate the EPIC measurements, a program package using the double-k approach was developed. Compared to line-by-line calculation, this approach can calculate high-accuracy results with a 100-fold computation time reduction. During the retrieval processes, two kinds of retrieval results, i.e., baseline CTP and retrieved CTP, are provided. The baseline CTP is derived without considering in-cloud photon penetration, and the retrieved CTP is derived by solving the analytic equation, taking into consideration in-cloud and below-cloud interactions. The retrieved CTPs for the oxygen A and B bands are smaller than their related baseline CTP. At the same time, both baseline CTP and retrieved CTP at the oxygen B band are larger than those at the oxygen A band. Compared to the difference in baseline CTP between the B band and A band, the difference in retrieved CTP between these two bands is generally reduced. Out of around 10 000 cases, in retrieved CTP between the A and B bands we found an average bias of 93 mb with a standard deviation of 81 mb. The cloud layer top pressure from Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) measurements is used for validation. Under single-layer cloud situations, the retrieved CTPs for the oxygen A band agree well with the CTPs from CALIPSO, the mean difference of which within 5 mb in the case study. Under multiple-layer cloud situations, the CTPs derived from EPIC measurements may be larger than the CTPs of high-level thin clouds due to the effect of photon penetration.
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van Dam, Lisette F., Lucia J. M. Kroft, Menno V. Huisman, Maarten K. Ninaber, and Frederikus A. Klok. "Computed Tomography Pulmonary Perfusion for Prediction of Short-Term Clinical Outcome in Acute Pulmonary Embolism." TH Open 05, no. 01 (January 2021): e66-e72. http://dx.doi.org/10.1055/s-0041-1723782.
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Abstract Background Computed tomography pulmonary angiography (CTPA) is the imaging modality of choice for the diagnosis of acute pulmonary embolism (PE). With computed tomography pulmonary perfusion (CTPP) additional information on lung perfusion can be assessed, but its value in PE risk stratification is unknown. We aimed to evaluate the correlation between CTPP-assessed perfusion defect score (PDS) and clinical presentation and its predictive value for adverse short-term outcome of acute PE. Patients and Methods This was an exploratory, observational study in 100 hemodynamically stable patients with CTPA-confirmed acute PE in whom CTPP was performed as part of routine clinical practice. We calculated the difference between the mean PDS in patients with versus without chest pain, dyspnea, and hemoptysis and 7-day adverse outcome. Multivariable logistic regression analysis and likelihood-ratio test were used to assess the added predictive value of PDS to CTPA parameters of right ventricle dysfunction and total thrombus load, for intensive care unit admission, reperfusion therapy and PE-related death. Results We found no correlation between PDS and clinical symptoms. PDS was correlated to reperfusion therapy (n = 4 with 16% higher PDS, 95% confidence interval [CI]: 3.5–28%) and PE-related mortality (n = 2 with 22% higher PDS, 95% CI: 4.9–38). Moreover, PDS had an added predictive value to CTPA assessment for PE-related mortality (from Chi-square 14 to 19, p = 0.02). Conclusion CTPP-assessed PDS was not correlated to clinical presentation of acute PE. However, PDS was correlated to reperfusion therapy and PE-related mortality and had an added predictive value to CTPA-reading for PE-related mortality; this added value needs to be demonstrated in larger studies.
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Bryar, Julie M., Carole Kathleen Dalby, Susan Anastas, Lauren Brady, Michael J. Hassett, Lawrence N. Shulman, and Joseph O. Jacobson. "Implementation of chemotherapy treatment plans (CTP) in a large comprehensive cancer center (CCC): The key roles of infrastructure and data sharing." Journal of Clinical Oncology 31, no. 31_suppl (November 1, 2013): 20. http://dx.doi.org/10.1200/jco.2013.31.31_suppl.20.
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20 Background: ASCO recommends that prior to initiating chemotherapy, a synoptic CTP should be created. At a large CCC, there was no tool to consistently or clearly communicate chemotherapy plans within the electronic health record (EHR). Methods: In 2011, a structured tool was created in the EHR to document patient diagnosis, tumor characteristics, planned regimen, side effects, performance status, and other elements when starting a new chemotherapy. Completion of a CTP generates a synoptic note in the EHR, pre-populates a chemotherapy consent form and computerized chemotherapy ordering template, helping to integrate CTPs into normal workflow and removing steps for possible errors. Completed CTPs can be accessed by care team members and sent to external referring providers. Implementation strategy included education on the importance of and how to complete CTPs and sending monthly compliance reports to disease centers (DC) and regional sites (RS). Compliance was defined as number completed CTPs / number new chemotherapy starts. Results: The CTP tool was introduced in a staggered rollout in mid-2011 (compliance reporting began in 2012). Six DC and 3 RS presently complete and use CTPs. 3,569 CTPs were completed since 2012. The table shows compliance by quarter, demonstrating significant variation among DC and RS. We attribute increased compliance to introduction of formal feedback reports that allow for identification of high-volume providers not completing CTPs, triggering individual interventions, especially targeted re-education. We also suspect shared reporting led to competition among providers, further improving performance. No incentives were provided for CTP completion. Conclusions: By creating a tool within the existing workflow and providing formal feedback, CTPs have been implemented as a communication tool at a CCC. [Table: see text]
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Zhang, Shanshan, Han-Chao Feng, and Ji-Long Liu. "ASNS disruption shortens CTPS cytoophidia in Saccharomyces cerevisiae." G3 Genes|Genomes|Genetics 11, no. 1 (January 1, 2021): 1–10. http://dx.doi.org/10.1093/g3journal/jkaa060.
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Abstract Asparagine synthetase (ASNS) and CTP synthase (CTPS) are two metabolic enzymes that catalyze the biosynthesis of asparagine and CTP, respectively. Both CTPS and ASNS have been identified to form cytoophidia in Saccharomyces cerevisiae. Glutamine is a common substrate for both these enzymes, and they play an important role in glutamine homeostasis. Here, we find that the ASNS cytoophidia are shorter than the CTPS cytoophidia, and that disruption of ASNS shortens the length of CTPS cytoophidia. However, the deletion of CTPS has no effect on the formation and length of ASNS cytoophidia, or on the ASNS protein level. We also find that Asn1 overexpression induces the formation of a multi-dot structure in diauxic phase which suggests that the increased protein level may trigger cytoophidia formation. Collectively, our results reveal a connection between ASNS cytoophidia and CTPS cytoophidia.
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Zhou, Xian, Chen-Jun Guo, Chia-Chun Chang, Jiale Zhong, Huan-Huan Hu, Guang-Ming Lu, and Ji-Long Liu. "Structural basis for ligand binding modes of CTP synthase." Proceedings of the National Academy of Sciences 118, no. 30 (July 23, 2021): e2026621118. http://dx.doi.org/10.1073/pnas.2026621118.
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Cytidine triphosphate synthase (CTPS), which comprises an ammonia ligase domain and a glutamine amidotransferase domain, catalyzes the final step of de novo CTP biosynthesis. The activity of CTPS is regulated by the binding of four nucleotides and glutamine. While glutamine serves as an ammonia donor for the ATP-dependent conversion of UTP to CTP, the fourth nucleotide GTP acts as an allosteric activator. Models have been proposed to explain the mechanisms of action at the active site of the ammonia ligase domain and the conformational changes derived by GTP binding. However, actual GTP/ATP/UTP binding modes and relevant conformational changes have not been revealed fully. Here, we report the discovery of binding modes of four nucleotides and a glutamine analog 6-diazo-5-oxo-L-norleucine in Drosophila CTPS by cryo–electron microscopy with near-atomic resolution. Interactions between GTP and surrounding residues indicate that GTP acts to coordinate reactions at both domains by directly blocking ammonia leakage and stabilizing the ammonia tunnel. Additionally, we observe the ATP-dependent UTP phosphorylation intermediate and determine interacting residues at the ammonia ligase. A noncanonical CTP binding at the ATP binding site suggests another layer of feedback inhibition. Our findings not only delineate the structure of CTPS in the presence of all substrates but also complete our understanding of the underlying mechanisms of the allosteric regulation and CTP synthesis.
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Seo, Jin, and Andrew J. Darwin. "The Pseudomonas aeruginosa Periplasmic Protease CtpA Can Affect Systems That Impact Its Ability To Mount Both Acute and Chronic Infections." Infection and Immunity 81, no. 12 (September 30, 2013): 4561–70. http://dx.doi.org/10.1128/iai.01035-13.
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ABSTRACTProteases play important roles in the virulence ofPseudomonas aeruginosa. Some are exported to act on host targets and facilitate tissue destruction and bacterial dissemination. Others work within the bacterial cell to process virulence factors and regulate virulence gene expression. Relatively little is known about the role of one class of bacterial serine proteases known as the carboxyl-terminal processing proteases (CTPs). TheP. aeruginosagenome encodes two CTPs annotated as PA3257/Prc and PA5134/CtpA in strain PAO1. Prc degrades mutant forms of the anti-sigma factor MucA to promote mucoidy in some cystic fibrosis lung isolates. However, nothing is known about the role or importance of CtpA. We have now found that endogenous CtpA is a soluble periplasmic protein and that actpAnull mutant has specific phenotypes consistent with an altered cell envelope. Although actpAnull mutation has no major effect on bacterial growth in the laboratory, CtpA is essential for the normal function of the type 3 secretion system (T3SS), for cytotoxicity toward host cells, and for virulence in a mouse model of acute pneumonia. Conversely, increasing the amount of CtpA above its endogenous level induces an uncharacterized extracytoplasmic function sigma factor regulon, an event that has been reported to attenuateP. aeruginosain a rat model of chronic lung infection. Therefore, a normal level of CtpA activity is critical for T3SS function and acute virulence, whereas too much activity can trigger an apparent stress response that is detrimental to chronic virulence.
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Fragata, Isabel, Marta Alves, Ana Luísa Papoila, Mariana Diogo, Patrícia Canhão, and Nuno Canto-Moreira. "Temporal evolution of cerebral computed tomography perfusion after acute subarachnoid hemorrhage: a prospective cohort study." Acta Radiologica 61, no. 3 (July 2, 2019): 376–85. http://dx.doi.org/10.1177/0284185119858701.
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Background Changes in cerebral perfusion occur in subarachnoid hemorrhage that possibly relate to clinical presentation and complications. Purpose To evaluate changes in computed tomography perfusion (CTP) parameters between the acute and subacute stage of subarachnoid hemorrhage. To analyze correlation of these parameters to SAH severity and delayed cerebral ischemia. Material and Methods Cerebral CT perfusion was assessed in a prospective cohort of 44 patients with acute subarachnoid hemorrhage at < 72 h (CTP1) and 8–10 days (CTP2), using the mean of all regions of interest. Regions of interest were located at arterial territories of the anterior, middle, and posterior cerebral artery and basal ganglia and midpons cerebellar hemispheres. Linear regression models (univariable and multivariable) were used to explore the association between changes in perfusion parameters (absolute and relative differences) and relevant clinical data. Results Worse perfusion parameters on the first 72 h were correlated with poor admission clinical scores: cerebral blood flow positively correlated with Glasgow Coma Scale (rS = 0.398, P = 0.008), and negatively correlated with Hunt & Hess scale (rS = −0.348, P = 0.020) and World Federation of Neurosurgeons scale (rS = −0.384, P = 0.010). Cerebral blood volume positively correlated with Glasgow Coma Scale (rS = 0.332, P = 0.028) and negatively correlated with World Federation of Neurosurgeons scale (rS = −0.353, P = 0.019). Mean transit time negatively correlated with Glasgow Coma Scale (rS = −0.415, P = 0.005) and positively correlated with Hunt & Hess scale (rS = 0.471, P = 0.001) and World Federation of Neurosurgeons scale (rS = 0.386, P = 0.010) scores. There were no differences between absolute CTP1/CTP2 parameters. Patients with delayed cerebral ischemia had ΔTmax mean decrease of 2.08 s (95% CI = −4.04–−0.12; P = 0.038). Conclusion Early cerebral hypoperfusion correlates with poor clinical grade at admission in subarachnoid hemorrhage and with higher amounts of blood. Tmax was decreased at 8–10 days, in patients with delayed cerebral ischemia, which may favor the application value of Tmax in signaling delayed cerebral ischemia.
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Meissner, Hermann, Marcel Cadet, Nicole Stephan, and Christian Bohr. "Model-Based Development Process of Cybertronic Products and Production Systems." Advanced Materials Research 1018 (September 2014): 539–46. http://dx.doi.org/10.4028/www.scientific.net/amr.1018.539.
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The shift to satisfied customer markets forces manufacturers to offer customised products. Moreover, product lifecycles are shortened, which requires a faster development of products and corresponding production systems. Both challenges amplify complexity in production. This complexity is usually confronted with flexibility. A new approach offering decentralised structures, and thereby flexibility, comes from cybertronic systems (CTS), which are further developed mechatronic systems with the capability to communicate through open networks with other such mechatronic systems. Up to now no integrated development process to engineer cybertronic products (CTP) and production systems (CTPS) has been developed, although such a process is essential to use their beneficial properties for today’s market conditions. Therefore, research is conducted in the research project mecPro². First, the properties of cybertronic systems are investigated and dissociated from those of mechatronic systems. Based on these properties, the connections of CTP and CTPS are analysed and a systematics for description for both is identified. With this the model-based development processes of CTP and CTPS can be further defined as well as their intersections and afterwards implemented in a data model. Finally, the development process is summarised in a product lifecycle management software to support the development process.
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Duan, Shuyin, Huijie Yuan, Songcheng Yu, Xiaoling Wei, Xiaoshan Zhou, Wei Wang, Feifei Feng, Lingbo Qu, and Yongjun Wu. "Epigenetic-Based Biomarkers in the Malignant Transformation of BEAS-2B Cells Induced by Coal Tar Pitch Extract." Medicina 57, no. 1 (December 29, 2020): 24. http://dx.doi.org/10.3390/medicina57010024.
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Background and objectives: The carcinogenicity of coal tar pitch (CTP) to occupational workers has been confirmed by the International Agency for Research on Cancer, especially for lung cancer. Herein, we explored the dynamic changes of epigenetic modifications in the malignant transformation process of CTP-induced BEAS-2B cells and also provided clues for screening early biomarkers of CTP-associated occupational lung cancer. Methods: BEAS-2B cells treated with 3.0 μg/mL CTP extract (CTPE) were cultured to the 30th passage to set up a malignant transformation model, which was confirmed by platelet clone formation assay and xenograft assay. DNA methylation levels were determined by ultraviolet-high performance liquid chromatography. mRNA levels in cells and protein levels in supernatants were respectively detected by Real-Time PCR and enzyme-linked immunosorbent assay. Results: The number of clones and the ability of tumor formation in nude mice of CTPE-exposed BEAS-2B cells at 30th passage were significantly increased compared to vehicle control. Moreover, genomic DNA methylation level was down-regulated. The mRNA levels of DNMT1, DNMT3a and HDAC1 as well as the expression of DNMT1 protein were up-regulated since the 10th passage. From the 20th passage, the transcriptional levels of DNMT3b, let-7a and the expression of DNMT3a, DNMT3b, and HDAC1 proteins were detected to be higher than vehicle control, while the level of miR-21 increased only at the 30th passage. Conclusion: Data in this study indicated that the changes of epigenetic molecules including DNMT1, DNMT3a, DNMT3b, HDAC1, and let-7a occurred at the early stages of BEAS-2B cell malignant transformation after CTPE exposure, which provided critical information for screening early biomarkers of CTP-associated occupational lung cancer.
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Sivasubramaniyan, Kavitha, Dragos C. Ilas, Abhishek Harichandan, Pieter K. Bos, Diego L. Santos, Peter de Zwart, Wendy J. L. M. Koevoet, et al. "Bone Marrow–Harvesting Technique Influences Functional Heterogeneity of Mesenchymal Stem/Stromal Cells and Cartilage Regeneration." American Journal of Sports Medicine 46, no. 14 (November 12, 2018): 3521–31. http://dx.doi.org/10.1177/0363546518804807.
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Background: Connective tissue progenitors (CTPs) from native bone marrow (BM) or their culture-expanded progeny, often referred to as mesenchymal stem/stromal cells, represents a promising strategy for treatment of cartilage injuries. But the cartilage regeneration capacity of these cells remains unpredictable because of cell heterogeneity. Hypothesis: The harvest technique of BM may highly influence stem cell heterogeneity and, thus, cartilage formation because these cells have distinct spatial localization within BM from the same bone. Study Design: Controlled laboratory study. Methods: CTPs obtained from the femur of patients undergoing total hip replacement by 2 harvest techniques—BM aspiration and BM collection—after bone rasping were immunophenotyped by flow cytometry and evaluated for chondrogenic ability. The spatial localization of different CTP subsets in BM was verified by immunohistochemistry. Results: Cells from the BM after rasping were significantly more chondrogenic than the donor-matched aspirate, whereas no notable difference in their osteogenic or adipogenic potential was observed. The authors then assessed whether distinct immunophenotypically defined CTP subsets were responsible for the different chondrogenic capacity. Cells directly isolated from BM after rasping contained a higher percentage (mean, 7.2-fold) of CD45–CD271+CD56+ CTPs as compared with BM aspirates. The presence of this subset in the harvested BM strongly correlated with chondrogenic ability, showing that CD271+CD56+ cells are enriched in chondroprogenitors. Furthermore, evaluation of these CTP subsets in BM revealed that CD271+CD56+ cells were localized in the bone-lining regions whereas CD271+CD56– cells were found in the perivascular regions. Since the iliac crest remains a frequent site of BM harvest for musculoskeletal regeneration, the authors also compared the spatial distribution of these subsets in trabeculae of femoral head and iliac crest and found CD271+CD56+ bone-lining cells in both tissues. Conclusion: Chondrogenically distinct CTP subsets have distinct spatial localization in BM; hence, the harvest technique of BM determines the efficiency of cartilage formation. Clinical Relevance: The harvest technique of BM may be of major importance in determining the clinical success of BM mesenchymal stem/stromal cells in cartilage repair.
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Fares, Fuad, Avri Havron, and Eyal Fima. "Designing a Long Acting Erythropoietin by Fusing Three Carboxyl-Terminal Peptides of Human Chorionic GonadotropinβSubunit to theN-Terminal andC-Terminal Coding Sequence." International Journal of Cell Biology 2011 (2011): 1–7. http://dx.doi.org/10.1155/2011/275063.
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A new analog of EPO was designed by fusing one and two CTPs to theN-terminal andC-terminal ends of EPO (EPO-(CTP)3), respectively. This analog was expressed and secreted efficiently in CHO cells. Thein vitrotest shows that the activity of EPO-(CTP)3in TFI-1 cell proliferation assay is similar to that of EPO-WT and commercial rHEPO. However,in vivostudies indicated that treatment once a week with EPO-(CTP)3(15 μg/kg) dramatically increased (~8 folds) haematocrit as it was compared to rHuEPO. Moreover, it was found that EPO-(CTP)3is more effective than rHuEPO and Aranesp in increasing reticulocyte number in mice blood. The detected circulatory half-lives of rHuEPO, Aranesp, and EPO-(CTP)3following IV injection of 20 IU were 4.4, 10.8, and 13.1 h, respectively. These data established the rational for using this chimera as a long-acting EPO analog in clinics. The therapeutic efficacy of EPO-CTP analog needs to be established in higher animals and in human clinical trials.
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Lee, Min, and Seong-Keun Oh. "Joint Power Allocation for Coordinated Multi-Point Diversity Transmission in Rayleigh Fading Channels." Electronics 8, no. 1 (January 16, 2019): 101. http://dx.doi.org/10.3390/electronics8010101.
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We consider the problem of joint power allocation (JPA) in a coordinated multi-point (CoMP) joint diversity transmission (JDT) network with a total coordination point power (TCPP) constraint, aimed at maximizing the ergodic cooperative capacity (ECC) in Rayleigh fading channels. In this paper, we first extend the JPA problem in the coordinated two-point (Co2P) JDT networkto the case of a non-unity TCPP constraint. Furthermore, we introduce more accurate log-quadratic approximated (LQA) expressions to obtain the coordinated transmission point (CTP) powers. Next, we extend our study to a coordinated three-point (Co3P) JDT network. Given the mean branch gain-to-noise ratios, we first obtain a log-linear approximated (LLA) expression for obtaining the optimum power of the third CTP (i.e., the worst quality-providing CTP). After obtaining the third-CTP power, we obtain the CTP powers of two better quality-providing CTPs by invoking the LLA CTP power expressions for Co2P JDT power allocation, under the remaining power given by the TCPP minus the third-CTP power. The numerical results demonstrate that the LQA and LLA CTP power expressions for Co2P JDT and the LLA CTP power expressions for Co3P JDT are very efficient in terms of the simplicity for JPA and CoMP set selection, as well as the resulting ECC.
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Raimunda, Daniel, Jarukit E. Long, Teresita Padilla-Benavides, Christopher M. Sassetti, and José M. Argüello. "Differential roles for the Co2+/Ni2+transporting ATPases, CtpD and CtpJ, inMycobacterium tuberculosisvirulence." Molecular Microbiology 91, no. 1 (November 20, 2013): 185–97. http://dx.doi.org/10.1111/mmi.12454.
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Mantripragada, Venkata P., Wes A. Bova, Nicolas S. Piuzzi, Cynthia Boehm, Nancy A. Obuchowski, Ronald J. Midura, and George F. Muschler. "Native-Osteoarthritic Joint Resident Stem and Progenitor Cells for Cartilage Cell-Based Therapies: A Quantitative Comparison With Respect to Concentration and Biological Performance." American Journal of Sports Medicine 47, no. 14 (October 31, 2019): 3521–30. http://dx.doi.org/10.1177/0363546519880905.
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Background: Cell-based therapy for cartilage repair is a promising approach and is becoming an established technique. Yet, there is no consensus on the optimal cell source. Purpose: To provide a donor-matched quantitative comparison of the connective tissue progenitors (CTPs) derived from cartilage (Outerbridge grade 1-3 [G1-2-3]), bone marrow aspirate concentrate (BMC), infrapatellar fat pad (IPFP), synovium, and periosteum with respect to (1) cell concentration ([Cell], cells/mL), (2) CTP prevalence (PCTP, colonies per million cells), and (3) biological performance based on in vitro proliferation potential (cells per colony) colony density, and differentiation potential (expression of negatively charged extracellular matrix: glycosaminoglycan-rich extra cellular matrix [GAG-ECM]). Study Design: Descriptive laboratory study. Methods: Tissues were obtained from 10 patients undergoing total knee arthroplasty (mean age, 59 years; women, n = 6). Automated quantitative colony-forming unit analysis was used to compare [Cell], PCTP, and CTP biological performance across tissue sources. Results: [Cell] was highest in grade 3 cartilage ( P = .002) and BMC ( P = .001). Median PCTP was highest in IPFP ( P = .001), synovium ( P = .003), and G1-2 cartilage ( P = .02). Proliferation was highest in synovium-derived CTPs ( P < .001). Median colony density was highest in G1-2-3 ( P < .001). Median GAG-ECM was highest in G1-2-3 ( P < .001). Within each patient, CTPs derived from all tissues were highly heterogeneous in biological performance as determined by cells per colony, density, and GAG-ECM. Conclusion: Tissue sources differ in [Cell], PCTP, and biological attributes. The data presented in this study suggest that cartilage (G1-2-3) is the preferred tissue source for cartilage repair based on PCTP and GAG-ECM, followed by synovium, IPFP, BMC, and periosteum. However, due to the heterogeneous mixture of CTPs within each tissue source, there exists a subset of CTPs with biological performance similar to G1-2-3 cartilage, particularly in synovium and IPFP. Performance-based clonal selection and expansion of preferred CTPs and their progeny will potentially lead to improved cell population with predictive future. Clinical Relevance: Optimal tissue regeneration strategies will require informed decisions regarding which of the available tissue sources to use. Optimizing cell sourcing in any tissue may require separation of CTPs with preferred attributes from those with less desirable attributes. The heterogeneity manifest in the early stage of colony formation represents an opportunity for performance-based clone selection for clinical cell processing and manufacturing.
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Poolsri, Wan-angkan, Phornpun Phokrai, Somrudee Suwankulanan, Narinthorn Phakdeeto, Pattamaphorn Phunsomboon, Dumrongsak Pekthong, Lysiane Richert, Sutatip Pongcharoen, and Piyarat Srisawang. "Combination of Mitochondrial and Plasma Membrane Citrate Transporter Inhibitors Inhibits De Novo Lipogenesis Pathway and Triggers Apoptosis in Hepatocellular Carcinoma Cells." BioMed Research International 2018 (2018): 1–15. http://dx.doi.org/10.1155/2018/3683026.
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Increased expression levels of both mitochondrial citrate transporter (CTP) and plasma membrane citrate transporter (PMCT) proteins have been found in various cancers. The transported citrates by these two transporter proteins provide acetyl-CoA precursors for the de novo lipogenesis (DNL) pathway to support a high rate of cancer cell viability and development. Inhibition of the DNL pathway promotes cancer cell apoptosis without apparent cytotoxic to normal cells, leading to the representation of selective and powerful targets for cancer therapy. The present study demonstrates that treatments with CTP inhibitor (CTPi), PMCT inhibitor (PMCTi), and the combination of CTPi and PMCTi resulted in decreased cell viability in two hepatocellular carcinoma cell lines (HepG2 and HuH-7). Treatment with citrate transporter inhibitors caused a greater cytotoxic effect in HepG2 cells than in HuH-7 cells. A lower concentration of combined CTPi and PMCTi promotes cytotoxic effect compared with either of a single compound. An increased cell apoptosis and an induced cell cycle arrest in both cell lines were reported after administration of the combined inhibitors. A combination treatment exhibits an enhanced apoptosis through decreased intracellular citrate levels, which consequently cause inhibition of fatty acid production in HepG2 cells. Apoptosis induction through the mitochondrial-dependent pathway was found as a consequence of suppressed carnitine palmitoyl transferase-1 (CPT-1) activity and enhanced ROS generation by combined CTPi and PMCTi treatment. We showed that accumulation of malonyl-CoA did not correlate with decreasing CPT-1 activity. The present study showed that elevated ROS levels served as an inhibition on Bcl-2 activity that is at least in part responsible for apoptosis. Moreover, inhibition of the citrate transporter is selectively cytotoxic to HepG2 cells but not in primary human hepatocytes, supporting citrate-mediating fatty acid synthesis as a promising cancer therapy.
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Yamauchi, Masatake, Noriko Yamauchi, Geraldine Phear, Nigel K. Spurr, Tommy Martinsson, Andreas Weith, and Mark Meuth. "Genomic organization and chromosomal localization of the human CTP synthetase gene (CTPS)." Genomics 11, no. 4 (December 1991): 1088–96. http://dx.doi.org/10.1016/0888-7543(91)90036-e.
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Chen, Yuan-Chuan, Hwei-Fang Cheng, and Ming-Kung Yeh. "Cell Therapy Regulation in Taiwan." Cell Transplantation 26, no. 3 (March 2017): 483–92. http://dx.doi.org/10.3727/096368916x693293.
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Cell therapy is not only a novel medical practice but also a medicinal product [cell therapy product (CTP)]. More and more CTPs are being approved for marketing globally because of the rapid development of bio-medicine in cell culture, preservation, and preparation. However, regulation is the most important criterion for the development of CTPs. Regulations must be flexible to expedite the process of marketing for new CTPs. Recently, the Taiwan Food and Drug Administration (TFDA) updated the related regulations such as regulation of development, current regulatory framework and process, and the application and evaluation processes. When the quality of CTPs has been improved significantly, their safety and efficacy are further ensured. The treatment protocol, a new design for adaptive licensing to current clinical practice, is a rapid process for patients with life-threatening diseases or serious conditions for which there are no suitable drugs, medical devices, or other therapeutic methods available. The hospital can submit the treatment protocol to apply for cell therapy as a medical practice, which may result in easier and faster cell therapy development, and personalized treatment for individual patients will evolve quickly.
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Correia, Luciano Lima, Hermano Alexandre Lima Rocha, Álvaro Jorge Madeiro Leite, Anamaria Cavalcante e Silva, Jocileide Sales Campos, Márcia Maria Tavares Machado, Ana Cristina Lindsay, and Antonio José Ledo Alves da Cunha. "The relation of cash transfer programs and food insecurity among families with preschool children living in semiarid climates in Brazil." Cadernos Saúde Coletiva 26, no. 1 (March 2018): 53–62. http://dx.doi.org/10.1590/1414-462x201800010341.
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Abstract Background Food insecurity has important effects on human health, particularly in children’s. It continues to increase, with an estimated prevalence of 14.9% in the USA and 35% in Brazil. There have been few studies on the effect of cash transfer programs (CTPs) on the prevalence of food security in Brazil. Objective Evaluate the association between cash transfer programs and reductions in inequity and food insecurity. Method Population-based cross-sectional study in the state of Ceará, Northeast Brazil, with a sample of 8.000 households. Ceará is one of the poorest states. The state population of 8.5 million inhabitants, social security benefits and government grants, “ Bolsa Família”, have become the most stable source of income. The main outcomes measures were food insecurity and CTP participation. Multivariate logistic models were constructed to assess the association between participation in CTPs and food security. Results Participation in CTPs was found to be independently related to the prevalence of food security (APR 2.29 95% CI 1.57-3.33), as are education level, residential setting, and children’s nutritional status. Conclusions CTPs and investment in education are initiatives that might be used to reduce food insecurity.
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Zhang, Wenjuan, Wenhong Tian, Shihua Song, Xianren Zeng, Peng Gao, Lili Mao, and Tiehu Li. "Effect of Different Catalysts on Properties of Coal Tar Pitch Modified by Cinnamaldehyde." Journal of Spectroscopy 2019 (March 3, 2019): 1–6. http://dx.doi.org/10.1155/2019/6040173.
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Cinnamaldehyde- (CMA-) modified coal tar pitches (CTPs) are prepared in the presence of acids. In this paper, the effect of boric acid and p-toluene sulfonic acid on the pyrolysis and graphitization process of CMA-modified CTP was studied. The pyrolysis process was studied by Fourier transform infrared spectroscopy, thermogravimetric analysis and derivative thermogravimetry, and polarized-light microscopy. In addition, the graphitization process was studied by X-ray diffraction and Raman spectroscopy. The results indicate the carbon yield of CMA-modified CTP with boric acid as catalyst (B7C10) is higher than that of CMA-modified CTP with p-toluene sulfonic acid as a catalyst (P7C10). In addition, under the same experimental condition (heated at 400°C and held for 1 h), the mesophase spheres of B7C10 are more regular than those of P7C10 and the largest diameter of the mesophase spheres can reach to 40 um. Further, after the graphitization process, the graphitization degree of B7C10 is higher than that of P7C10. So, it is more effective to modify CTP with boric acid as a catalyst.
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Murakami, Keisuke. "A generalized model and a heuristic algorithm for the large-scale covering tour problem." RAIRO - Operations Research 52, no. 2 (April 2018): 577–94. http://dx.doi.org/10.1051/ro/2017090.
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The covering tour problem (CTP) is defined on a graph, where there exist two types of vertices. One is called visited vertex, which can be visited. The other is called covered vertex, which must be covered but cannot be visited. Each visited vertex covers a subset of covered vertices, and the costs of edges between visited vertices are given. The objective of the CTP is to obtain a minimum cost tour on a subset of visited vertices while covering all covered vertices. In this paper, we deal with the large-scale CTPs, which are composed of tens of thousands of vertices; in the previous studies, the scales of the instances in the experiments are at most a few hundred vertices. We propose a heuristic algorithm using local search techniques for the large-scale CTP. With computational experiments, we show that our algorithm outperforms the existing methods.
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Põldvere, Nele, Matteo Fuoli, and Carita Paradis. "A study of dialogic expansion and contraction in spoken discourse using corpus and experimental techniques." Corpora 11, no. 2 (August 2016): 191–225. http://dx.doi.org/10.3366/cor.2016.0092.
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This study examines the dialogic functions of expansion and contraction of first-person epistemic and evidential Complement-Taking Predicate (CTP) constructions, such as I think complement, I suppose complement and I know complement, in spoken discourse. It combines corpus and experimental methods (i) to investigate whether CTP constructions are used to open up the dialogic space for new ideas or counterarguments, or to fend off alternative views, and (ii) to identify what contextual factors play a role in determining the dialogic force of the constructions. First, an exploratory analysis of CTP constructions in the London–Lund Corpus (LLC) of spoken British English is carried out with the aim to identify important contextual factors and generate hypotheses about their dialogic effects. Then, a laboratory experiment is conducted to test the impact of the three most prominent factors for speakers' interpretations of utterances containing CTPs. The results indicate that CTP constructions do not only serve to expand the dialogic context in which they occur, but also to restrict alternative views. Interlocutor status, the co-occurrence of other stance markers and prosodic marking of first-person CTP are shown to have a significant effect on the dialogic function of the expressions. These findings call into question some claims in appraisal theory about the role of CTP constructions in discourse, and highlight the need for a flexible approach to the analysis of these poly-functional stance expressions.
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Li, Jun, W. Paul Menzel, Wenjian Zhang, Fengying Sun, Timothy J. Schmit, James J. Gurka, and Elisabeth Weisz. "Synergistic Use of MODIS and AIRS in a Variational Retrieval of Cloud Parameters." Journal of Applied Meteorology 43, no. 11 (November 1, 2004): 1619–34. http://dx.doi.org/10.1175/jam2166.1.
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Abstract The Moderate Resolution Imaging Spectroradiometer (MODIS) and the Atmospheric Infrared Sounder (AIRS) measurements from the Earth Observing System's (EOS's) Aqua satellite enable global monitoring of the distribution of clouds. MODIS is able to provide a cloud mask, surface and cloud types, cloud phase, cloud-top pressure (CTP), effective cloud amount (ECA), cloud particle size, and cloud optical thickness at high spatial resolution (1–5 km). The combined MODIS–AIRS system offers the opportunity for improved cloud products, better than from either system alone; this improvement is demonstrated in this paper with both simulated and real radiances. A one-dimensional variational (1DVAR) methodology is used to retrieve the CTP and ECA from AIRS longwave (650–790 cm−1 or 15.38–12.65 μm) cloudy radiance measurements (hereinafter referred to as MODIS–AIRS 1DVAR). The MODIS–AIRS 1DVAR cloud properties show significant improvement over the MODIS-alone cloud properties and slight improvement over AIRS-alone cloud properties in a simulation study, while MODIS–AIRS 1DVAR is much more computationally efficient than the AIRS-alone 1DVAR; comparisons with radiosonde observations show that CTPs improve by 10–40 hPa for MODIS–AIRS CTPs over those from MODIS alone. The 1DVAR approach is applied to process the AIRS longwave cloudy radiance measurements; results are compared with MODIS and Geostationary Operational Environmental Satellite sounder cloud products. Data from ground-based instrumentation at the Atmospheric Radiation Measurement Program Cloud and Radiation Test Bed in Oklahoma are used for validation; results show that MODIS–AIRS improves the MODIS CTP, especially in low-level clouds. The operational use of a high-spatial-resolution imager, along with information from a high-spectral-resolution sounder will be possible with instruments planned for the next-generation geostationary operational instruments.
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Serena, Thomas E., Raphael A. Yaakov, and Eliot N. Mostow. "Use of Cellular and Tissue-based Product in the Treatment of Diabetic Foot Ulcers." Journal of Foot and Ankle Surgery (Asia Pacific) 3, no. 2 (2016): 92–96. http://dx.doi.org/10.5005/jp-journals-10040-1055.
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ABSTRACT Introduction The prevalence of diabetes has been rising sharply and the rise in chronic wounds parallels this trend. Lower extremity ulcers present a serious complication for people with diabetes. While debridement of necrotic tissue and off-loading plays an important role in wound healing, many patients with diabetic foot ulcers (DFUs) fail to heal with standard of care (SOC) alone. Unresolved ulcers can lead to complications, such as osteomyelitis and amputation. There continues to be a need for the evaluation of novel wound therapies that can accelerate wound healing and lower the cost of care associated with DFUs. This paper presents recent evidence for the use of cellular and/or tissue-based products (CTPs) and offers an approach for selecting an appropriate CTP. Materials and methods A systematic literature search was conducted using PubMed, Embase, Medline, Cochrane library, and NHS Economic Evaluation Database. Full-length articles in English were assessed for relevance to select studies on effectiveness and economic evaluations. Additionally, Google Scholar was used to gather relevant literature on commonly used CTPs, including Apligraf®, EpiFix®, and Dermagraft®. Findings Results from randomized controlled trials (RCTs) provided evidence for the superior efficacy of CTPs over SOC alone in treatment of chronic DFUs. In recent studies evaluating commonly used CTPs, significantly higher number of DFUs achieved complete closure with EpiFix® when compared to either Apligraf® or Dermagraft®. While cost-effectiveness studies continue to be limited, current literature suggests that CTPs can decrease the long-term costs associated with the care of DFUs by increasing the healing rate, reducing recovery time, and lowering the risk of infection and complications. Cellular and/or tissue-based products (CTPs) may result in higher average number of ulcer-free months and lower average number of amputations or resections compared to SOC alone. How to cite this article Serena TE, Yaakov RA, Mostow EN. Use of Cellular and Tissue-based Product in the Treatment of Diabetic Foot Ulcers. J Foot Ankle Surg (Asia-Pacific) 2016;3(2):92-96.
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Sydow, Mateusz, Łukasz Chrzanowski, Alexandra Leclerc, Alexis Laurent, and Mikołaj Owsianiak. "Terrestrial Ecotoxic Impacts Stemming from Emissions of Cd, Cu, Ni, Pb and Zn from Manure: A Spatially Differentiated Assessment in Europe." Sustainability 10, no. 11 (November 8, 2018): 4094. http://dx.doi.org/10.3390/su10114094.
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Metallic elements present in livestock manure as co-contaminants have the potential to cause terrestrial ecotoxic impacts when the manure is used as fertilizer on agricultural soils. The magnitude of this impact at country scale in Europe has, to date, not been quantified. Here, we address this knowledge gap by combining recently developed national emission inventories of Cd, Cu, Ni, Pb and Zn releases from manure with metal- and soil-specific comparative toxicity potentials (CTP) calculated for cropland grid cells at 1 × 1 km resolution for 33 European countries. The CTPs account for speciation in environmental fate, exposure and effects, including reduction in the solid-phase reactivity of a metal when it is associated with organic carbon present in the manure. Given the scarcity of inventory data at sub-national level, it was assumed that each unit area of cropland within a given country has the same probability to receive manure. The resulting CTPs span a range of several orders of magnitude reflecting the influence of soil type and properties on the speciation patterns and resulting CTP values. However, when combined with the use of manure in each European country, the resulting national impact scores were mainly explained by the total mass input of metal released to soil rather than by geographic variability in the CTP values. Simple linear regression is then sufficient to predict terrestrial ecotoxic impacts from input mass. Although some changes in ranking of metals and countries were observed, both mass- and impact-based comparisons between metals agreed that Zn and Cu are dominant contributors to total impacts, and that top contributing countries were those emitting the largest amounts of metals. Our findings show that spatially differentiated impact assessment is important for ranking of countries when differences in national emission inventories between countries are smaller than a factor of two (Ni), a factor of three (Cd, Cu, Zn) or a factor of four (Pb). In other cases, ranking of countries can be based on national emission inventories.
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Ai-Jalodi, Omar, Matthew Sabo, Keyur Patel, Neal Bullock, Laura Serena, Kristy Breisinger, and Thomas E. Serena. "Efficacy and safety of a porcine peritoneum-derived matrix in diabetic foot ulcer treatment: a pilot study." Journal of Wound Care 30, Sup2 (February 1, 2021): S18—S23. http://dx.doi.org/10.12968/jowc.2021.30.sup2.s18.
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Objective: A third of people with diabetes will develop a foot ulcer during their lifetime. The absence of pain secondary to neuropathy often leads to a delay in diagnosis and treatment. Diabetic foot ulcer (DFU) complications, such as infection and amputation, increase mortality and strain the financial resources of health systems across the world. Cellular and/or tissue products (CTPs) have played an important role in the closure of DFUs. Investigators continue to search for new CTPs that facilitate healing. The aim of this study was to assess the efficacy and safety of a porcine peritoneum-derived matrix in DFU treatment. Method: Patients with longstanding DFUs participated in this institutional review board-approved, multicentre, prospective pilot study evaluating the time to healing over 12 weeks. In addition to weekly assessments for wound size, investigators analysed bacterial burden using the MolecuLight procedure (MLiX) and bacterial protease (BPA) testing. Participants received a weekly application of Meso Wound Matrix Scaffold (MWM), a lyophilised porcine peritoneum-derived matrix (DSM Biomedical Inc., Exton, PA, US) for up to eight weeks. Descriptive statistics were chosen for this analysis. Results: A total of 12 male patients and three female patients with an average age of 57 years were enrolled over a two-month period. The average wound duration was 30 weeks. Due to unrelated health issues, four participants were withdrawn. For the study endpoint of complete wound closure at 12 weeks, six (55%) of the remaining 11 patients achieved complete closure, and four (36%) patients healed during the 8-week treatment period. The average number of CTP applications was six. Patients who healed all had negative BPA by nine weeks and no fluorescence on MLiX, indicating low bacterial load. Conclusion: This small pilot study indicates that patients with longstanding DFUs may respond to a porcine peritoneal-derived CTP. In this study, the CTP appears to have inhibited bacterial growth in the wound; however, further research is needed.
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Gerislioglu, Burak, and Arash Ahmadivand. "The Role of Electron Transfer in the Nonlinear Response of Ge2Sb2Te5-Mediated Plasmonic Dimers." Photonics 6, no. 2 (May 16, 2019): 52. http://dx.doi.org/10.3390/photonics6020052.
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Here, we study the possibility of exquisitely selective harmonic generation based on the concept of charge transfer plasmons (CTPs) in bridged nanoparticle assemblies. By choosing plasmonic dimer nanoantenna, as a fundamental member of the nanocluster family, and bridging the capacitive gap space between the proximal nanoparticles with an optothermally controllable substance, we judiciously showed that variations in the generation of third harmonic light in the visible regime can be possible by considering distinct states of the functional bridge. To this end, the conductive connection between the nanoparticles is mediated with Ge2Sb2Te5 (GST) with inherently opposite optical and electrical properties below (dielectric, amorphous state) and above 477 °C (conductive, crystalline state). This helped to actively control the transition of charges across the bridge and thereby control the excitation of CTP resonances and provide a switching feature between dipolar and CTP modes. This versatile approach also allowed for production of the intended harmonic signal at different wavelengths depending on the conductivity of the interparticle nanojunction.
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Ruskan, Anna. "Epistemic qualifications of the English marker likely and its equivalents in Lithuanian." Kalbotyra 69, no. 69 (January 27, 2017): 179. http://dx.doi.org/10.15388/klbt.2016.10372.
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The current study focuses on the epistemic qualifications realised by the English adjective and adverb likely and its equivalents in Lithuanian panašu ‘likely, it seems’ and tikėtina ‘believable, likely’, which derive from the semantic domain of comparison and belief. The aim of the study is to identify the functional similarities and differences of the markers in terms of their frequency, syntactic features (Complement-Taking-Predicates (CTPs), adverbials), functions, collocational profile and type of discourse (academic, newspaper). The English and Lithuanian data were drawn from the monolingual corpora, namely the Corpus of Contemporary American English (COCA), Corpus of the Contemporary Lithuanian Language (CCLL), Corpus of Academic Lithuanian (CorALit) and the bidirectional parallel corpus ParaCorpENàLTàEN. The quantitative and qualitative findings reveal that the closest cross-linguistic CTP and adverbial equivalents are likely and tikėtina ‘believable, likely’ because they are most frequent in formal registers (academic, newspaper discourse) and display similar collocational profiles and contexts of use. In contexts with explicit evidence and argumentation, they may acquire evidential functions. Although the CTP and adverbial panašu ‘likely, it seems’ shares similarities with likely and tikėtina ‘believable, likely’ in expressing the author’s degree of probability, it shows a different semantic profile from the latter due to its conceptual link with the original meaning of similarity and appearances. The study shows how markers that derive from the semantic domain of comparison vary in functional distribution in present-day English and Lithuanian and introduces their functional equivalents deriving from a different semantic domain.
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Sophia Chen, Yun-Chia, Brad J. Fabbri, Claire A. CaJacob, John C. Anderson, and Stephen M. G. Duff. "Suppression of CtpA in Mouseearcress Produces a Phytotoxic Effect: Validation of CtpA as a Target for Herbicide Development." Weed Science 55, no. 4 (August 2007): 283–87. http://dx.doi.org/10.1614/ws-07-019.
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To validate carboxyterminal processing protease of D1 protein (CtpA) as a target for herbicide discovery, CtpA sense mRNAs were overexpressed to suppress the internal level of CtpA protein in mouseearcress plants. Using antibodies raised against recombinant CtpA protein, we demonstrated that we have generated transgenic mouseearcress plants with reduced levels of CtpA protein and plants with elevated levels of CtpA protein. Transgenic plants with severely reduced levels of CtpA protein exhibited a bleached and chlorotic phenotype and stunted growth. The mutant phenotypes were enhanced by bright illumination. However, plants with a slight reduction of CtpA protein did not exhibit the mutant phenotype and could not be distinguished from wild-type plants under normal growth conditions. Several CtpA enzyme inhibitors were shown to have herbicidal activity in planta. Interestingly, plants producing excessive amount of CtpA protein were shown to be resistant to these inhibitors. Our results suggest that CtpA is essential for plant growth and development, but a reduced amount of CtpA is sufficient to carry out its essential function. CtpA may be a good target for herbicide development, but very high levels of inhibition may be required to produce a herbicidal effect. In addition, overexpressing CtpA in target plants might provide a mechanism for producing plants resistant to the herbicide.
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Godoy, Thais Galhardo, and Sebastião Carlos da Silva Rosado. "Efficiency of phosphorus use in young plants of Eucalyptus urophylla S. T. Blake." CERNE 17, no. 3 (September 2011): 303–8. http://dx.doi.org/10.1590/s0104-77602011000300003.
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The objective of this study is to select superior genotypes for efficiency of phosphorus use in seedlings of Eucalyptus urophylla, correlating them with initial height growth in the field, at age eight months. Acompletely randomized block design was used in the nursery, consisting of eight clones, three replicates and four plants per plot. The same design was used in the field, consisting of eight clones, four replicate blocks and nine plants per plot. Data being collected in the nursery at age 120 days included: phosphorus concentration in shoot (CPPA); phosphorus concentration in root (CPR); phosphorus content in shoot (CtPPA); phosphorus content in root (CtPR); total phosphorus content in seedling (CtPT); phosphorus use efficiency in shoot (EUP-PA); phosphorus use efficiency in root (EUP-R) and total phosphorus use efficiency (EUP-T). Analyses of variance showed significant genetic differences among clones for all traits and, given the high heritability values found, estimated genetic gains were generically very high. As regards predicted indirect genetic gain, it was noted that selection on nursery seedlings for all EUPs provided the highest values of indirect gain in height of field seedlings.
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Konopińska, Kamila, Mariusz Pietrzak, Radosław Mazur, and Elżbieta Malinowska. "Analytical characterization of IgG–cTpp and IgG–Mn-cTpp conjugates." Journal of Porphyrins and Phthalocyanines 19, no. 11 (November 2015): 1177–84. http://dx.doi.org/10.1142/s1088424615500984.
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Herein, the conjugation of carboxylated tetraphenylporphyrin or its derivative containing manganese cation and model protein — immunoglobulin G is presented. The obtained IgG–cTpp and IgG–Mn-cTpp conjugates were subsequently used for model immunoassays construction. The IgG–cTpp formation was confirmed using size-exclusion chromatography. Thanks to the unique properties of applied labels the assay analysis was carried out with both spectrophotometric and spectrofluorimetric detection. The assays were performed creating semi-quantitative detection system using 96-well plates. The incubation time, ensuring full saturation of the surface with secondary antibodies was also optimized. Moreover, in the case of IgG–Mn-cTpp conjugates we present the possibility of both direct and indirect determination of the label, the latter based on the catalytic activity of Mn-cTpp, which allows for amplification of the measured signal. We proved that both cTpp and Mn-cTpp may be successfully used for protein labeling and serve as universal tracers for various formats of affinity assays and sensors.
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Langel, Crt, and Katarina Surlan Popovic. "Infarct-core CT perfusion parameters in predicting post-thrombolysis hemorrhagic transformation of acute ischemic stroke." Radiology and Oncology 53, no. 1 (December 20, 2018): 25–30. http://dx.doi.org/10.2478/raon-2018-0048.
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Abstract Background Intravenous thrombolysis (IVT) is the method of choice in reperfusion treatment of patients with signs and symptoms of acute ischemic stroke (AIS) lasting less than 4.5 hours. Hemorrhagic transformation (HT) of acute ischemic stroke is a serious complication of IVT and occurs in 4.5–68.0% of clinical cases. The aim of our study was to determine the infarct core CT perfusion parameter (CTPP) most predictive of HT. Patients and methods Seventy-five patients with AIS who had undergone CT perfusion (CTP) imaging and were treated with IVT were enrolled in this retrospective study. Patients with and without HT after IVT were defined as cases and controls, respectively. Controls were found by matching for time from AIS symptom onset to IVT ± 0.5 h. The following CTPPs were measured: cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), relative CBF (rCBF) and relative CBV (rCBV). Receiver operating characteristic analysis curves of significant CTPPs determined cut-off values that best predict HT. Results There was a significant difference between cases and controls for CBF (p = 0.004), CBV (p = 0.009), rCBF (p < 0.001) and rCBV (p = 0.001). Receiver operating characteristic analysis revealed that rCBF < 4.5% of the contralateral mean (area under the curve = 0.736) allowed prediction of HT with a sensitivity of 71.0% and specificity of 52.5%. Conclusions CTP imaging has a considerable role in HT prediction, assisting in selection of patients that are likely to benefit from IVT. rCBF proved to have the highest HT predictive value.
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Gnawali, Omprakash, Rodrigo Fonseca, Kyle Jamieson, Maria Kazandjieva, David Moss, and Philip Levis. "CTP." ACM Transactions on Sensor Networks 10, no. 1 (November 2013): 1–49. http://dx.doi.org/10.1145/2529988.
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Östberg, Yngve, James A. Carroll, Marija Pinne, Jonathan G. Krum, Patricia Rosa, and Sven Bergström. "Pleiotropic Effects of Inactivating a Carboxyl-Terminal Protease, CtpA, in Borrelia burgdorferi." Journal of Bacteriology 186, no. 7 (April 1, 2004): 2074–84. http://dx.doi.org/10.1128/jb.186.7.2074-2084.2004.
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ABSTRACT A gene encoding a putative carboxyl-terminal protease (CtpA), an unusual type of protease, is present in the Borrelia burgdorferi B31 genome. The B. burgdorferi CtpA amino acid sequence exhibits similarities to the sequences of the CtpA enzymes of the cyanobacterium Synechocystis sp. strain PCC 6803 and higher plants and also exhibits similarities to the sequences of putative CtpA proteins in other bacterial species. Here, we studied the effect of ctpA gene inactivation on the B. burgdorferi protein expression profile. Total B. burgdorferi proteins were separated by two-dimensional gel electrophoresis, and the results revealed that six proteins of the wild type were not detected in the ctpA mutant and that nine proteins observed in the ctpA mutant were undetectable in the wild type. Immunoblot analysis showed that the integral outer membrane protein P13 was larger and had a more acidic pI in the ctpA mutant, which is consistent with the theoretical change in pI for P13 not processed at the carboxyl terminus. Matrix-assisted laser desorption ionization—time of flight data indicated that in addition to P13, the BB0323 protein may serve as a substrate for carboxyl-terminal processing by CtpA. Complementation analysis of the ctpA mutant provided strong evidence that the observed effect on proteins depended on inactivation of the ctpA gene alone. We show that CtpA in B. burgdorferi is involved in the processing of proteins such as P13 and BB0323 and that inactivation of ctpA has a pleiotropic effect on borrelial protein synthesis. To our knowledge, this is the first analysis of both a CtpA protease and different substrate proteins in a pathogenic bacterium.
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Lee, Bae-Kyu. "Multi-channel LD - Driver designed for CTP(computer to plate)." Journal of the Korea Institute of Information and Communication Engineering 19, no. 3 (March 31, 2015): 667–73. http://dx.doi.org/10.6109/jkiice.2015.19.3.667.
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Radhiah, Sitti, Kiki Sanjaya, and Pitriani Pitriani. "Pendampingan Cuci Tangan Pakai Sabun di SDN Al-Akbar Petobo." Jurnal Dedikatif Kesehatan Masyarakat 1, no. 1 (October 9, 2020): 44–50. http://dx.doi.org/10.22487/dedikatifkesmas.v1i1.155.
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Kejadian penyakit menular merupakan hal yang sangat mengkhawatirkan terutama pada anak-anak usia sekolah. Kejadian penyakit menular dapat dicegah dan dikendalikan laju penularannya melalui upaya Cuci Tangan Pakai Sabun (CTPS) khususnya pada lima waktu penting. Bahkan saat ini, CTPS menjadi salah satu anjuran kunci WHO dalam mencegah penularan Covid-19 yang mewabah sejak akhir 2019. Siswa/siswi sekolah dasar memiliki potensi sebagai “Agent of Change” untuk mempromosikan CTPS di sekolah, keluarga dan masyarakat. Perubahan perilaku pada anak sekolah sejak dini diharapkan akan menjadi kebiasaan baik hingga usia dewasa. Fakta inilah yang mendasari digagasnya upaya pendampingan CTPS di SDN Al-Akbar Petobo sebagai upaya perubahan perilaku siswa dalam mempraktekkan CTPS. Untuk menudukung perubahan perilaku siswa, maka telah disediakan 2 buah sarana CTPS di sekolah tepatnya di area depan kelas. Selain menyediakan sarana CTPS juga dilakukan edukasi melalui media sosial. Materi edukasi yang disajikan dalam bentuk video yang memuat tentang pentingnya CTPS, 5 waktu penting CTPS dan langkah-langkah CTPS sesuai standar WHO. Video dikirimkan kepada guru wali kelas untuk selanjutnya disebarkan ke group belajar siswa/siswi mengingat pembelajaran saat ini sebagian besar berbasis online. Video edukasi CTPS juga disebarkan secara luas melalui FB dan Instagram mahasiswa Peminatan Kesehatan Lingkungan FKM UNTAD.
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KASAKURA, Akeo. "Thermal CTP Plate." Kobunshi 51, no. 11 (2002): 897. http://dx.doi.org/10.1295/kobunshi.51.897.
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Janik, Piotr, Anna Dunalska, Natalia Szejko, and Andrzej Jakubczyk. "Cognitive Tic-Like Phenomena in Gilles de la Tourette Syndrome." Journal of Clinical Medicine 10, no. 13 (June 22, 2021): 2749. http://dx.doi.org/10.3390/jcm10132749.
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Coprolalia and echophenomena repeated in the patients’ mind (CTPh—cognitive tic-like phenomena) have been rarely recognized as part of Gilles de la Tourette syndrome (GTS) symptomatology and their assignment to tics, OCD or other psychopathologies has not been settled. The aim of the paper was to assess the incidence and clinical associations of CTPh in GTS, and to establish if CTPh belong to the tic spectrum. We performed a prospective, one-registration study on a cohort of 227 consecutive patients with GTS. CTPh were diagnosed during the interview and defined as brief, sudden, involuntary thoughts that had corresponding complex vocal tics. CTPh occurred at some point in the lives of 34 (15.0%) patients. The median age at onset of CTPh was 14.5 years (IQR: 10.5–17.5). CTPh were found more frequently in adults, with the most frequent onset in adolescence (44.1%). Four mental phenomena resembling tics were recognized: echolalia (n = 17), coprolalia (n = 16), palilalia (n = 13) and repeating of words in the mind (n = 7). The older the age of patients, the more severe tics, and anxiety disorder significantly correlated with CTPh. CTPh may be considered as a part of tic spectrum with a substantial impact of anxiety disorder. CTPh are a late and age-related symptom of GTS.
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Aggarwal, Tanya, Ali Eskandari, Sarv Priya, Aidan Mullan, Ishan Garg, Jakub Siembida, Brian Mullan, and Prashant Nagpal. "Pulmonary embolism rule out: positivity and factors affecting the yield of CT angiography." Postgraduate Medical Journal 96, no. 1140 (January 5, 2020): 594–99. http://dx.doi.org/10.1136/postgradmedj-2019-137031.
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ObjectiveCT pulmonary angiography (CTPA) is one of the most commonly ordered CT imaging tests. It is often believed to be overutilised with few recent studies showing a yield of less than 2%. This study aimed to determine the overall positivity rate of CTPA examinations and understand the factors that affect the yield of the CTPA examination.MethodsWe retrospectively analysed 2713 patients who received the CTPA exam between 2016 and 2018. Type of study ordered (CTPA chest or CTPA chest with abdomen and pelvis CT), patient location (emergency department (ED), outpatient, inpatient, intensive care unit (ICU)) and patient characteristics—age, sex and body mass index (BMI) were recorded. A logistic regression analysis was performed to determine what factors affect the positivity rate of CT scans for pulmonary embolism (PE).ResultsWith 296 positive test results, the overall CTPA positivity was 10.9%. Male sex was associated with higher CTPA positivity, gender difference was maximum in 18-year to 35-year age group. Overweight and obese patients had significantly higher positivity as compared with BMI<25 (p<0.05). Higher positivity rate was seen in the BMI 25–40 group (11.9%) as compared with BMI>40 (10.1%) (p<0.05). Significant difference (p<0.001) was also found in CTPA examination yield from ICU (15.3%) versus inpatients (other than ICU) (12.4%) versus ED (9.6%), and outpatients (8.5%). The difference in CTPA yield based on the type of CT order (CTPA chest vs CTPA chest with CT abdomen and pelvis), patient’s age and sex was not significant.ConclusionCTPA yield of 10.9% in this study is comparable to acceptable positivity rate for the USA and is higher than recent studies showing positivity of <2%. Patient characteristics like obesity and ICU or inpatient location are associated with higher rate of CT positivity.
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Shujaat, Adil, Janet M. Shapiro, and Edward Eden. "Utilization of CT Pulmonary Angiography in Suspected Pulmonary Embolism in a Major Urban Emergency Department." Pulmonary Medicine 2013 (2013): 1–6. http://dx.doi.org/10.1155/2013/915213.
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Objectives. We conducted a study to answer 3 questions: (1) is CT pulmonary angiography (CTPA) overutilized in suspected pulmonary embolism (PE)? (2) What alternative diagnoses are provided by CTPA? (3) Can CTPA be used to evaluate right ventricular dilatation (RVD)?Methods. We retrospectively reviewed the clinical information of 231 consecutive emergency department patients who underwent CTPA for suspected PE over a one-year period.Results. The mean age of our patients was 53 years, and 58.4% were women. The prevalence of PE was 20.7%. Among the 136 patients with low clinical probability of PE, a d-dimer test was done in 54.4%, and it was normal in 24.3%; none of these patients had PE. The most common alternative findings on CTPA were emphysema (7.6%), pneumonia (7%), atelectasis (5.5%), bronchiectasis (3.8%), and congestive heart failure (3.3%). The sensitivity and negative predictive value of CTPA for (RVD) was 92% and 80%, respectively.Conclusions. PE could have been excluded without CTPA in ~1 out of 4 patients with low clinical probability of PE, if a formal assessment of probability and d-dimer test had been done. In patients without PE, CTPA did not provide an alternative diagnosis in 65%. In patients with PE, CTPA showed the potential to evaluate RVD.
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Dong, Lina, Wenying Zhou, Xuezhen Sui, Zijun Wang, Peng Wu, Jing Zuo, Huiwu Cai, and Xiangrong Liu. "Thermal, mechanical, and dielectric properties of epoxy resin modified using carboxyl-terminated polybutadiene liquid rubber." Journal of Elastomers & Plastics 49, no. 4 (June 29, 2016): 281–97. http://dx.doi.org/10.1177/0095244316653261.
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Epoxy (Ep) resin modified with carboxyl-terminated polybutadiene (CTPB) liquid rubber was investigated in this study. Fourier transform infrared verified the chemical reactions between oxirane ring of Ep and carboxyl groups of CTPB using benzyldimethylamine as a catalyst. The decrease of the thermal stability could be due to the lower thermal stability of CTPB compared with that of pure Ep. The mechanical results showed that CTPB-modified Ep was superior to that of the pure Ep, and the best overall mechanical properties were normally achieved with 20 phr of CTPB content. The impact strength of the system containing 20 phr CTPB increased by 193% due to the two-phase nature of the system. The dielectric constant and dissipation factor of the modified Ep obviously declined with the CTPB content compared with pure Ep, for instance, the dissipation factor remained less than 0.02 in wide frequency range.
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Aldosari, Sultan, and Zhonghua Sun. "A Systematic Review of Double Low-dose CT Pulmonary Angiography in Pulmonary Embolism." Current Medical Imaging Formerly Current Medical Imaging Reviews 15, no. 5 (June 19, 2019): 453–60. http://dx.doi.org/10.2174/1573405614666180813120619.
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Background: The aim of this study is to perform a systematic review of the feasibility and clinical application of double low-dose CT pulmonary angiography (CTPA) in the diagnosis of patients with suspected pulmonary embolism. Discussion: A total of 13 studies were found to meet selection criteria reporting both low radiation dose (70 or 80 kVp versus 100 or 120 kVp) and low contrast medium dose CTPA protocols. Lowdose CTPA resulted in radiation dose reduction from 29.6% to 87.5% in 12 studies (range: 0.4 to 23.5 mSv), while in one study, radiation dose was increased in the dual-energy CT group when compared to the standard 120 kVp group. CTPA with use of low contrast medium volume (range: 20 to 75 ml) was compared to standard CTPA (range: 50 to 101 ml) in 12 studies with reduction between 25 and 67%, while in the remaining study, low iodine concentration was used with 23% dose reduction achieved. Quantitative assessment of image quality (in terms of signal-to-noise ratio and contrast-to-noise ratio) showed that low-dose CTPA was associated with higher, lower and no change in image quality in 3, 3 and 6 studies, respectively when compared to the standard CTPA protocol. The subjective assessment indicated similar image quality in 11 studies between low-dose and standard CTPA groups, and improved image quality in 1 study with low-dose CTPA. Conclusion: This review shows that double low-dose CTPA is feasible in the diagnosis of pulmonary embolism with significant reductions in both radiation and contrast medium doses, without compromising diagnostic image quality.
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Cebon, J. S., S. Svobodova, J. Browning, I. D. Davis, R. Scolyer, R. Murali, J. F. Thompson, S. Deb, A. Azad, and D. MacGregor. "Prognostic impact of cancer-testis antigen expression in primary cutaneous melanoma." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 9004. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.9004.
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9004 Background: Cancer-testis antigens (CTAg) are epigenetically regulated molecules expressed in many cancers including melanoma. Although functional studies are limited, they are often immunogenic making them attractive targets for immunotherapy. In normal tissues expression is restricted to germ cells and a small range of other tissues such as trophoblast. Previous studies have shown that CTAg expression increases with disease progression. We investigated whether the expression of three CTAgs, against which vaccines have been developed, may have prognostic significance in early stage melanoma. Methods: 233 AJCC Stage II melanomas were analyzed for expression of MAGE-A1, MAGE-A4 and NY-ESO-1 by immunohistochemistry. The relationship between CTAg expression, clinico-pathological features and relapse free survival (RFS) from initial diagnosis were correlated. Mutivariate analysis using known prognostic factors and CT Ag expression in the model were used to calculate hazard ratios. Results: All three CTAg were significantly co-expressed with each other (P=0.0001). RFS was reduced if tumors expressed any of these CTAgs (CTAg+ve). Median RFS for patients with CTAg+ve tumors was 45m versus 72m for those with CTAg-ve tumors (P=0.008, logrank test). Univariate analysis demonstrated that the impact of CTAg expression on RFS was comparable in magnitude to ulceration, Breslow thickness and mitotic rate, currently accepted prognostic factors. Multivariate analysis demonstrated CTAg expression, ulceration and thickness but not mitotic rate were independently associated with poorer RFS ( Table ). Conclusions: CTAg expression in cutaneous primary melanoma has impact on prognosis comparable to Breslow thickness ulceration and mitotic rate. Further study into their function and the impact of clinical targeting is warranted. [Table: see text] No significant financial relationships to disclose.
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Lamba, Jatinder, Amit Mitra, Kristine Crews, Pounds Stanley, Xueyuan Cao, Varsha Gandhi, William Plunkett, Jeffrey Rubnitz, and Raul Ribeiro. "Pathway Based Pharmacogenomics of Cytarabine In Pediatric Acute Myeloid Leukemia." Blood 116, no. 21 (November 19, 2010): 294. http://dx.doi.org/10.1182/blood.v116.21.294.294.
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Abstract Abstract 294 Acute myeloid leukemia (AML) is the second most common form of childhood leukemia and has the worst prognosis of all major childhood cancers. The mainstay of AML chemotherapy is the nucleoside analog cytarabine (ara-C). Numerous studies suggest that the intracellular concentrations of the ara-C active metabolite, ara-CTP, vary widely among patients, and in turn, are associated with variability in clinical response to AML treatment. In the present study, we have taken a pathway directed approach to identify genetic predictors of ara-C response in pediatric patients treated with ara-C based antileukemic chemotherapy in the AML02 (n=187) and AML97 (n=55) clinical trials. The AML02 trial enrolled AML patients <22 years of age excluding APL or Down's syndrome patients, but those with all other subtypes of de novo or secondary AML, as well as patients with mixed-lineage leukemia, were eligible. Patients were randomized to receive induction I therapy containing high-dose cytarabine or low-dose cytarabine plus daunorubicin and etoposide. We genotyped the genomic DNA from patients enrolled in AML02 study for potentially significant single nucleotide polymorphisms (SNPs) in 10 key ara-C pathway genes and screened for association with 3 endpoints in AML02 study: in vitro ara-C LC50 determined in diagnostic leukemic cells, event free survival (EFS) and overall survival (OS). In samples from St. Jude AML97 study, we screened for association of SNPs with 4 endpoints: intracellular ara-CTP levels after start of induction, DNA synthesis relative to baseline, morphological response after induction I, and EFS. In the St Jude AML 97 study patients were randomly assigned to receive ara-C as either a short daily infusion (500 mg/m2/dose intravenously over 2 hrs daily for 5 days) or a continuous infusion (500 mg/m2/day as a continuous infusion over 5 days). Bone marrow was collected at the end of the ara-C infusion on day 1 for patients receiving the short daily infusion (n=27), and at 10 hrs after the start of the infusion for those receiving the continuous infusion (n=28). Ara-CTP levels in leukemia cells were analyzed by HPLC. Intracellular accumulation of ara-CTP was significantly higher when given as short daily infusion, as compared to continuous infusion (p = 0.01). The inter-patient variability for blast ara-CTP concentrations was 40-fold in the short infusion arm and 101-fold in the continuous infusion arm. We found significant correlations between SNPs in ara-C pathway genes (such as DCK, DCTD, CMPK, CTPS, CDA and NT5C2) and various clinical parameters (after adjusting for arm and/or risk group), some of which are listed below. These results suggest that genetic variation in key candidate genes in ara-C metabolic pathway could in?uence and predict the variability observed in cellular sensitivity and treatment response. The pharmacogenomic factors identi?ed in the present study could be potentially used for tailoring medications to better individualize cytarabine based AML therapy. Disclosures: No relevant conflicts of interest to declare.
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Salehi, L., P. Phalpher, D. Levay, C. Meaney, M. Ossip, R. Valani, and M. Mercuri. "P113: Variability in utilization and diagnostic yield of computed tomography (CT) scans for pulmonary embolism among emergency physicians." CJEM 21, S1 (May 2019): S105. http://dx.doi.org/10.1017/cem.2019.304.
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Introduction: Current data on utilization of CT imaging point to a trend of increasing overutilization of CT Angiography for the diagnosis of pulmonary embolism (CTPA) over time. Multiple educational and institution-wide interventions addressing this overutilization have been proposed, implemented and evaluated, with mixed results in terms of long-term impact on physician ordering behaviour. The objective of this study is to examine the inter-physician variability in ordering rates and diagnostic yield of CTPA, under a working hypothesis that a small number of physicians are responsible for a disproportionately high number of CTPA ordered in the ED. Methods: Data was collected on all CTPA studies ordered by ED physicians at two very high volume community hospitals and an affiliated urgent care centre during the 2-year period between January 1, 2016 and December 31, 2017. Analysis was limited to those ED physicians who had a total of greater than 500 ED visits over the course of the 2-year period. For each physician, two calculations were made: 1) CT PE ordering rate (total number of CTPA ordered divided by the total number of ED visits), and 2) CTPA diagnostic yield (total number of CTPA positive for PE divided by the total number CTPA ordered). Additional analysis was carried out in order to identify the highest orderers of CTPA and their diagnostic yield. Results: A total of 2,789 CTPA were ordered by 84 physicians for 461,045 total ED visits. Preliminary results show a great deal of variation in ordering rates, ranging from 0.9 to 22.2 CTPA per 1000 ED visit (median = 4.8, IQR = 4.5). Similarly, there was high variation in CT PE yield, ranging from 0% to 50% (median = 9.6%, IQR = 13.1%). Those physicians in the top quartile for ordering rate had a lower mean diagnostic yield, when compared to the lower quartiles (8.9% when compared to 11.5%, 11.9% and 18.2% for the physicians in the third, second, and first quartile respectively). Conclusion: The findings of this study indicate a wide degree of variability in CTPA ordering patterns and diagnostic yield among physicians working within the same clinical environment. There is some suggestion that those physicians who order disproportionately higher numbers of CTPAs have lower diagnostic yields. However, the more interesting lessons from this initial study center on the challenges in creating an audit-and-feedback program targeting CTPA ‘overutilizers’.
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Cui, Zijin, Haiqing Yang, Xiaoxu Jin, Huiqing Jiang, Wei Qi, Wenfeng Feng, and Zhijie Feng. "Efficacy of CTPV for Diagnostic and Therapeutic Assessment: Comparison with Endoscopy in Cirrhotic Patients with Gastroesophageal Varices." Gastroenterology Research and Practice 2020 (June 5, 2020): 1–10. http://dx.doi.org/10.1155/2020/6268570.
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Background and Aims. Computed tomography portal venography (CTPV) shows potential in detecting varices that need treatment and their drainage pathways. However, its agreement with endoscopy requires further study. We investigated the feasibility of CTPV as an alternative tool to endoscopy in screening gastroesophageal varices (GEVs) and developed a CTPV-based model to provide a less invasive assessment of endotherapy for cirrhotic patients with GEVs. Methods. The study included 33 cirrhotic patients with a recent history of variceal hemorrhage. The presence, grade, and classification of GEVs on endoscopy and CTPV were compared (kappa test). Twenty-four patients were treated endoscopically, including 12 for esophageal varices (EVs), 8 for gastric varices (GVs), and 4 for GEVs. Treatment efficacies were assessed with the newly developed CTPV-based method at 1 week and 1 month after treatment. Efficiency evaluated by CTPV and endoscopy was compared by Fisher’s exact test to determine whether CTPV is efficient in the assessment of endotherapy efficacy. Results. For the screening and grading/classification of EVs and GVs, substantial agreement (EV kappa: 0.63 and 0.68; GV kappa: 0.62 and 0.75, respectively) was noted between endoscopy and CTPV. The therapeutic efficacy of EVs was higher when assessed by CTPV than when evaluated by endoscopy (37.50% vs. 12.50% at 1 week postoperation, P=0.22; 62.50% vs. 25.00% at 1 month postoperation, P=0.07), but without statistical significance. The same trend was also found in the assessment of therapeutic efficacy for GVs (25.00% vs. 16.67% at 1 week postoperation, P=1; 58.33% vs. 41.67% at 1 month postoperation, P=0.68). Conclusion. CTPV is comparable to endoscopy in the detection of GEVs and in the evaluation of endotherapy efficacy, which suggests that it could be a less invasive alternative for endoscopy in cirrhotic patients with GEVs needing treatment.