Isolation of a euryhaline microalgal strain, Tetraselmis sp. CTP4, as a robust feedstock for biodiesel production

PubMed Central

Pereira, Hugo; Gangadhar, Katkam N.; Schulze, Peter S. C.; Santos, Tamára; de Sousa, Carolina Bruno; Schueler, Lisa M.; Custódio, Luísa; Malcata, F. Xavier; Gouveia, Luísa; Varela, João C. S.; Barreira, Luísa

2016-01-01

Bioprospecting for novel microalgal strains is key to improving the feasibility of microalgae-derived biodiesel production. Tetraselmis sp. CTP4 (Chlorophyta, Chlorodendrophyceae) was isolated using fluorescence activated cell sorting (FACS) in order to screen novel lipid-rich microalgae. CTP4 is a robust, euryhaline strain able to grow in seawater growth medium as well as in non-sterile urban wastewater. Because of its large cell size (9–22 μm), CTP4 settles down after a six-hour sedimentation step. This leads to a medium removal efficiency of 80%, allowing a significant decrease of biomass dewatering costs. Using a two-stage system, a 3-fold increase in lipid content (up to 33% of DW) and a 2-fold enhancement in lipid productivity (up to 52.1 mg L−1 d−1) were observed upon exposure to nutrient depletion for 7 days. The biodiesel synthesized from the lipids of CTP4 contained high levels of oleic acid (25.67% of total fatty acids content) and minor amounts of polyunsaturated fatty acids with ≥4 double bonds (<1%). As a result, this biofuel complies with most of the European (EN14214) and American (ASTM D6751) specifications, which commonly used microalgal feedstocks are usually unable to meet. In conclusion, Tetraselmis sp. CTP4 displays promising features as feedstock with lower downstream processing costs for biomass dewatering and biodiesel refining. PMID:27767051

Towards robust deconvolution of low-dose perfusion CT: sparse perfusion deconvolution using online dictionary learning.

PubMed

Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C

2013-05-01

Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

De-agglomeration and homogenisation of nanoparticles in coal tar pitch-based carbon materials

NASA Astrophysics Data System (ADS)

Gubernat, Maciej; Tomala, Janusz; Frohs, Wilhelm; Fraczek-Szczypta, Aneta; Blazewicz, Stanislaw

2016-03-01

The aim of the work was to characterise coal tar pitch (CTP) modified with selected nanoparticles as a binder precursor for the manufacture of synthetic carbon materials. Different factors influencing the preliminary preparative steps in the preparation of homogenous nanoparticle/CTP composition were studied. Graphene flakes, carbon black and nano-sized silicon carbide were used to modify CTP. Prior to introducing them into liquid CTP, nanoparticles were subjected to sonication. Various dispersants were used to prepare the suspensions, i.e. water, ethanol, dimethylformamide (DMF) and N-methylpyrrolidone (NMP).The results showed that proper dispersant selection is one of the most important factors influencing the de-agglomeration process of nanoparticles. DMF and NMP were found to be effective dispersants for the preparation of homogenous nanoparticle-containing suspensions. The presence of SiC and carbon black nanoparticles in the liquid pitch during heat treatment up to 2000 °C leads to the inhibition of crystallite growth in carbon residue.

Towards robust deconvolution of low-dose perfusion CT: Sparse perfusion deconvolution using online dictionary learning

PubMed Central

Fang, Ruogu; Chen, Tsuhan; Sanelli, Pina C.

2014-01-01

Computed tomography perfusion (CTP) is an important functional imaging modality in the evaluation of cerebrovascular diseases, particularly in acute stroke and vasospasm. However, the post-processed parametric maps of blood flow tend to be noisy, especially in low-dose CTP, due to the noisy contrast enhancement profile and the oscillatory nature of the results generated by the current computational methods. In this paper, we propose a robust sparse perfusion deconvolution method (SPD) to estimate cerebral blood flow in CTP performed at low radiation dose. We first build a dictionary from high-dose perfusion maps using online dictionary learning and then perform deconvolution-based hemodynamic parameters estimation on the low-dose CTP data. Our method is validated on clinical data of patients with normal and pathological CBF maps. The results show that we achieve superior performance than existing methods, and potentially improve the differentiation between normal and ischemic tissue in the brain. PMID:23542422

Enhanced bone formation in the vicinity of porous β-TCP scaffolds exhibiting slow release of collagen-derived tripeptides.

PubMed

Kamikura, Keita; Minatoya, Tsutomu; Terada-Nakaishi, Michiko; Yamamoto, Shoko; Sakai, Yasuo; Furusawa, Toshitake; Matsushima, Yuta; Unuma, Hidero

2017-09-01

It has been experimentally proven that orally ingested collagen-derived tripeptides (Ctp) are quickly absorbed in the body and effectively promote the regeneration of connective tissues including bone and skin. Ctp are capable to activate osteoblasts and fibroblasts, which eventually promotes tissue regeneration. Based on these findings, a hypothesis was formulated in this study that direct delivery of Ctp to bone defect would also facilitate tissue regeneration as well as oral administration. To test the hypothesis, we prepared a bone augmentation material with the ability to slowly release Ctp, and investigated its in vivo bone regeneration efficacy. The implant material was porous β-tricalcium phosphate (β-TCP) scaffold which was coated with a co-precipitated layer of bone-like hydroxyapatite and Ctp. The β-TCP was impregnated with approximately 0.8%(w/w) Ctp. Then, the Ctp-modified β-TCP was implanted into bone defects of Wistar rats to evaluate in vivo efficacy of Ctp directly delivered from the material to the bone defects. The control was pristine porous β-TCP. In vitro tests showed that Ctp were steadily released from the co-precipitated layer for approximately two weeks. The Ctp-modified scaffolds significantly promoted new bone formation in vivo in their vicinity as compared with pristine β-TCP scaffolds; 6 weeks after the implantation, Ctp-modified scaffolds promoted twice as much bone formation as the control implants. Consequently, we achieved the slow and steady release of Ctp, and found that direct delivery of Ctp from implant materials was effective for bone regeneration as well as oral administration. A β-TCP scaffold capable of slowly releasing bone-enhancing substances significantly promoted bone formation.

Description of the datasets for the experiments in the paper "solving the multi-vehicle multi-covering tour problem".

PubMed

Pham, Tuan Anh; Hà, Minh Hoàng; Nguyen, Xuan Hoai

2018-06-01

This data article contains data related to the research article entitled, "Solving the multi-vehicle multi-covering tour problem" (Pham et al., 2017) [4]. All data of this article was generated from instances kroA100, kroB100, kroC100, kroD100, kroA200, and kroB200 from TSPLIB. It can be downloaded from public repository. This data can be used as benchmarks for the covering tour problem (CTP) variants, such as m -CTP- p , m -CTP, mm -CTP- p , mm -CTP, mm -CTP-o, mm -CTP-wo. We tested our algorithm on these data and results are shown in Pham et al. (2017) [4].

The carboxyl-terminal region is a determinant for the intracellular behavior of the chorionic gonadotropin beta subunit: effects on the processing of the Asn-linked oligosaccharides.

PubMed

Muyan, M; Boime, I

1998-05-01

The placental hormone human CG (hCG) consists of two noncovalently linked alpha- and beta-subunits similar to the other glycoprotein hormones LH, FSH, and TSH. These heterodimers share a common alpha subunit but differ in their structurally distinct beta subunits. The CGbeta subunit is distinguished among the beta subunits by the presence of a C-terminal extension with four serine-linked oligosaccharides (carboxyl terminal peptide or CTP). In previous studies we observed that deleting this sequence decreased assembly of the truncated CGbeta subunit (CGbeta114) with the alpha-subunit and increased the heterogeneity of the secreted forms of the uncombined subunit synthesized in transfected Chinese hamster ovary (CHO) cells. The latter result was attributed to alterations in the processing of the two N-linked oligosaccharides. To examine at what step this heterogeneity occurs, the CGbeta and CGbeta114 genes were transfected into wild-type and mutant CHO cell lines that are defective in the late steps of the N-linked carbohydrate-processing pathway. We show here that removal of the CTP alters the processing of the core mannosyl unit of the subunit to complex forms at both glycosylation sites and that the oligosaccharides contain polylactosamine. Although it has been presumed that there is little intramolecular interaction between the CTP and the proximal domains of the subunit, our data suggest that the CTP sequence participates in the folding of the newly synthesized subunit, which is manifest by the posttranslational changes observed here.

Time-Dependent Computed Tomographic Perfusion Thresholds for Patients With Acute Ischemic Stroke.

PubMed

d'Esterre, Christopher D; Boesen, Mari E; Ahn, Seong Hwan; Pordeli, Pooneh; Najm, Mohamed; Minhas, Priyanka; Davari, Paniz; Fainardi, Enrico; Rubiera, Marta; Khaw, Alexander V; Zini, Andrea; Frayne, Richard; Hill, Michael D; Demchuk, Andrew M; Sajobi, Tolulope T; Forkert, Nils D; Goyal, Mayank; Lee, Ting Y; Menon, Bijoy K

2015-12-01

Among patients with acute ischemic stroke, we determine computed tomographic perfusion (CTP) thresholds associated with follow-up infarction at different stroke onset-to-CTP and CTP-to-reperfusion times. Acute ischemic stroke patients with occlusion on computed tomographic angiography were acutely imaged with CTP. Noncontrast computed tomography and magnectic resonance diffusion-weighted imaging between 24 and 48 hours were used to delineate follow-up infarction. Reperfusion was assessed on conventional angiogram or 4-hour repeat computed tomographic angiography. Tmax, cerebral blood flow, and cerebral blood volume derived from delay-insensitive CTP postprocessing were analyzed using receiver-operator characteristic curves to derive optimal thresholds for combined patient data (pooled analysis) and individual patients (patient-level analysis) based on time from stroke onset-to-CTP and CTP-to-reperfusion. One-way ANOVA and locally weighted scatterplot smoothing regression was used to test whether the derived optimal CTP thresholds were different by time. One hundred and thirty-two patients were included. Tmax thresholds of >16.2 and >15.8 s and absolute cerebral blood flow thresholds of <8.9 and <7.4 mL·min(-1)·100 g(-1) were associated with infarct if reperfused <90 min from CTP with onset <180 min. The discriminative ability of cerebral blood volume was modest. No statistically significant relationship was noted between stroke onset-to-CTP time and the optimal CTP thresholds for all parameters based on discrete or continuous time analysis (P>0.05). A statistically significant relationship existed between CTP-to-reperfusion time and the optimal thresholds for cerebral blood flow (P<0.001; r=0.59 and 0.77 for gray and white matter, respectively) and Tmax (P<0.001; r=-0.68 and -0.60 for gray and white matter, respectively) parameters. Optimal CTP thresholds associated with follow-up infarction depend on time from imaging to reperfusion. © 2015 American Heart Association, Inc.

CTP (Cochlin-tomoprotein) detection in the profuse fluid leakage (gusher) from cochleostomy.

PubMed

Ikezono, Tetsuo; Sugizaki, Kazuki; Shindo, Susumu; Sekiguchi, Satomi; Pawankar, Ruby; Baba, Shunkichi; Yagi, Toshiaki

2010-08-01

By testing 125 samples, we confirmed that Cochlin-tomoprotein (CTP) is present in the perilymph, not in cerebrospinal fluid (CSF). Perilymph and CSF exist in two distinct compartments, even in the case of a malformed inner ear with a bony defect in the lamina cribrosa, as described here. Cochleostomy might have suddenly decreased the perilymph pressure, allowing the influx of CSF into the inner ear resulting in profuse fluid leakage, first perilymph then CSF. The first purpose of this study was to further confirm the specificity of the perilymph-specific protein CTP that we reported recently. Secondly, we assessed the nature of the fluid leakage from the cochleostomy using the CTP detection test. A standardized CTP detection test was performed on 65 perilymph and 60 CSF samples. Samples of profuse fluid leakage collected from cochleostomy during cochlear implantation surgery of one patient with branchio-oto-renal (BOR) syndrome were also tested by the CTP detection test. CTP was detected in 60 of 65 perilymph samples but not in any of the CSF samples. The leaked fluid was shown to contain CTP, i.e. perilymph, at the outset, and then the CTP detection signals gradually disappeared as time elapsed.

Creatinine-modified Child-Turcotte-Pugh score is a good predictor of a short-term survival in patients with bleeding from esophageal varices.

PubMed

Radisavljević, Mirjana; Bjelaković, Goran; Jović, Jasna; Radovanović-Dinić, Biljana; Benedoto-Stojanov, Danijela; Brzački, Vesna; Marković-Živković, Bojana

2017-01-01

Bleeding from esophageal varices is a significant factor in mortality of patients with terminal liver cirrhosis. This complication is a major health problem for recipients on the list for liver transplant. In that regard, studying predictors of variceal bleeding episode is very important. Also, it is important to find the best survival predictor among prognostic scores. The aim of the study was to compare validity of prognostic scores in assessment of survival in hospital-treated patients after bleeding from esophageal varices, and to compare validity of baseline Child-Turcotte-Pugh (CTP) and Modul for End-stage Liver Disease (MELD) scores with CTP creatinine modified (CTP-crea) I and II scores in assessment of survival in patients within a long-term follow-up period after the episode of bleeding from esophageal varices. The study included a total of 126 patients suffering from terminal liver cirrhosis submited to testing CTP score score I and II, MELD score, MELD Na score, integrated MELD score, MELD sodium (MESO) index, United Kingdom Model for End-Stage Liver Disease (UKELD) score and updated MELD score. Patients with bleeding from esophageal varices most often had CTP score rank C (46,9%). CTP score rank B had 37.5% patients, while the smallest percentage of patients had CTP rank A, 15.6% of them. Patients who have values of CTP score higher than 10.50 and bleeding from esophagus, have 3.2 times higher chance for death outcome compared to other patients. Patients who have values of CTP-crea I score higher than 10.50 and bleeding from esophagus, have 3.1 times higher chance for death out-come than other patients. Patients who have values of CTP-crea II score higher than 11.50 and bleeding from esophagus, have 3,7 times higher chance for death outcome compared to other patients. Survival of patients with bleeding from esophageal varices in the short-term follow up can be predicted by following CTP score and creatinine modified CTP scores. Patients with bleeding from esophageal varices who have CTP score and CTP-crea I score higher than 10.5 and CTP-crea II score higher than 11.5, have statistically significantly higher risk from mortality within one-month follow-up compared to patients with bleeding from esophageal varices who have lower numerical values of scores of the CTP group.

Development of oral CTL vaccine using a CTP-integrated Sabin 1 poliovirus-based vector system.

PubMed

Han, Seung-Soo; Lee, Jinjoo; Jung, Yideul; Kang, Myeong-Ho; Hong, Jung-Hyub; Cha, Min-Suk; Park, Yu-Jin; Lee, Ezra; Yoon, Cheol-Hee; Bae, Yong-Soo

2015-09-11

We developed a CTL vaccine vector by modification of the RPS-Vax system, a mucosal vaccine vector derived from a poliovirus Sabin 1 strain, and generated an oral CTL vaccine against HIV-1. A DNA fragment encoding a cytoplasmic transduction peptide (CTP) was integrated into the RPS-Vax system to generate RPS-CTP, a CTL vaccine vector. An HIV-1 p24 cDNA fragment was introduced into the RPS-CTP vector system and a recombinant poliovirus (rec-PV) named vRPS-CTP/p24 was produced. vRPS-CTP/p24 was genetically stable and efficiently induced Th1 immunity and p24-specific CTLs in immunized poliovirus receptor-transgenic (PVR-Tg) mice. In challenge experiments, PVR-Tg mice that were pre-immunized orally with vRPS-CTP/p24 were resistant to challenge with a lethal dose of p24-expressing recombinant vaccinia virus (rMVA-p24). These results suggested that the RPS-CTP vector system had potential for developing oral CTL vaccines against infectious diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Medical cannabis and mental health: A guided systematic review.

PubMed

Walsh, Zach; Gonzalez, Raul; Crosby, Kim; S Thiessen, Michelle; Carroll, Chris; Bonn-Miller, Marcel O

2017-02-01

This review considers the potential influences of the use of cannabis for therapeutic purposes (CTP) on areas of interest to mental health professionals, with foci on adult psychopathology and assessment. We identified 31 articles relating to the use of CTP and mental health, and 29 review articles on cannabis use and mental health that did not focus on use for therapeutic purposes. Results reflect the prominence of mental health conditions among the reasons for CTP use, and the relative dearth of high-quality evidence related to CTP in this context, thereby highlighting the need for further research into the harms and benefits of medical cannabis relative to other therapeutic options. Preliminary evidence suggests that CTP may have potential for the treatment of PTSD, and as a substitute for problematic use of other substances. Extrapolation from reviews of non-therapeutic cannabis use suggests that the use of CTP may be problematic among individuals with psychotic disorders. The clinical implications of CTP use among individuals with mood disorders are unclear. With regard to assessment, evidence suggests that CTP use does not increase risk of harm to self or others. Acute cannabis intoxication and recent CTP use may result in reversible deficits with the potential to influence cognitive assessment, particularly on tests of short-term memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is cannabis an illicit drug or a medicine? A quantitative framing analysis of Israeli newspaper coverage.

PubMed

Sznitman, Sharon R; Lewis, Nehama

2015-05-01

Various countries and states, including Israel, have recently legalized cannabis for therapeutic purposes (CTP). These changes have received mass media coverage and prompted national and international dialogue about the status of cannabis and whether or not it can be defined as a (legitimate) medicine, illicit and harmful drug, or both. News media framing may influence, and be influenced by, public opinion regarding CTP and support for CTP license provisions for patients. This study examines the framing of CTP in Israeli media coverage and the association between media coverage and trends in the provision of CTP licenses in Israel over time. All published news articles relevant to CTP and the framing of cannabis (N=214) from the three highest circulation newspapers in Israel were content analyzed. Articles were published between January 2007 and June 2013, a period in which CTP licenses granted by the Ministry of Health increased substantially. In the majority of CTP news articles (69%), cannabis was framed as a medicine, although in almost one third of articles (31%) cannabis was framed as an illicit drug. The relative proportion of news items in which cannabis was framed as an illicit drug fluctuated during the study period, but was unrelated to linear or curvilinear trends in CTP licensing. The relatively large proportion of news items framing cannabis as a medicine is consistent with growing support for the expansion of the Israel's CTP program. Copyright © 2015 Elsevier B.V. All rights reserved.

Time-resolved perfusion imaging at the angiography suite: preclinical comparison of a new flat-detector application to computed tomography perfusion.

PubMed

Jürgens, Julian H W; Schulz, Nadine; Wybranski, Christian; Seidensticker, Max; Streit, Sebastian; Brauner, Jan; Wohlgemuth, Walter A; Deuerling-Zheng, Yu; Ricke, Jens; Dudeck, Oliver

2015-02-01

The objective of this study was to compare the parameter maps of a new flat-panel detector application for time-resolved perfusion imaging in the angiography room (FD-CTP) with computed tomography perfusion (CTP) in an experimental tumor model. Twenty-four VX2 tumors were implanted into the hind legs of 12 rabbits. Three weeks later, FD-CTP (Artis zeego; Siemens) and CTP (SOMATOM Definition AS +; Siemens) were performed. The parameter maps for the FD-CTP were calculated using a prototype software, and those for the CTP were calculated with VPCT-body software on a dedicated syngo MultiModality Workplace. The parameters were compared using Pearson product-moment correlation coefficient and linear regression analysis. The Pearson product-moment correlation coefficient showed good correlation values for both the intratumoral blood volume of 0.848 (P < 0.01) and the blood flow of 0.698 (P < 0.01). The linear regression analysis of the perfusion between FD-CTP and CTP showed for the blood volume a regression equation y = 4.44x + 36.72 (P < 0.01) and for the blood flow y = 0.75x + 14.61 (P < 0.01). This preclinical study provides evidence that FD-CTP allows a time-resolved (dynamic) perfusion imaging of tumors similar to CTP, which provides the basis for clinical applications such as the assessment of tumor response to locoregional therapies directly in the angiography suite.

Cannabis for therapeutic purposes and public health and safety: a systematic and critical review.

PubMed

Sznitman, Sharon R; Zolotov, Yuval

2015-01-01

The use of Cannabis for Therapeutic Purposes (CTP) has recently become legal in many places. These policy and legal modifications may be related to changes in cannabis perceptions, availability and use and in the way cannabis is grown and sold. This may in turn have effects on public health and safety. To better understand the potential effects of CTP legalization on public health and safety, the current paper synthesizes and critically discusses the relevant literature. Twenty-eight studies were identified by a comprehensive search strategy, and their characteristics and main findings were systematically reviewed according to the following content themes: CTP and illegal cannabis use; CTP and other public health issues; CTP, crime and neighbourhood disadvantage. The research field is currently limited by a lack of theoretical and methodological rigorous studies. The review shows that the most prevalent theme of investigation so far has been the relation between CTP and illegal cannabis use. In addition, the literature review shows that there is an absence of evidence to support many common concerns related to detrimental public health and safety effects of CTP legalization. Although lack of evidence provides some reassurance that CTP legalization may not have posed a substantial threat to public health and safety, this conclusion needs to be examined in light of the limitations of studies conducted so far. Furthermore, as CTP policy continues to evolve, including incorporation of greater commercialization, it is possible that the full effects of CTP legalization have yet to take place. Ensuring study quality will allow future research to better investigate the complex role that CTP plays in relation to society at large, and public health and safety in particular. Copyright © 2014 Elsevier B.V. All rights reserved.

Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study

PubMed Central

Yoo, Dae Hyun; Prodanovic, Nenad; Jaworski, Janusz; Miranda, Pedro; Ramiterre, Edgar; Lanzon, Allan; Baranauskaite, Asta; Wiland, Piotr; Abud-Mendoza, Carlos; Oparanov, Boycho; Smiyan, Svitlana; Kim, HoUng; Lee, Sang Joon; Kim, SuYeon; Park, Won

2017-01-01

Objectives To assess the efficacy and safety of switching from the infliximab reference product (RP; Remicade) to its biosimilar CT-P13 (Remsima, Inflectra) or continuing CT-P13 in patients with rheumatoid arthritis (RA) for an additional six infusions. Methods This open-label extension study recruited patients with RA who had completed the 54-week, randomised, parallel-group study comparing CT-P13 with RP (PLANETRA; NCT01217086). CT-P13 (3 mg/kg) was administered intravenously every 8 weeks from weeks 62 to 102. All patients received concomitant methotrexate. Endpoints included American College of Rheumatology 20% (ACR20) response, ACR50, ACR70, immunogenicity and safety. Data were analysed for patients who received CT-P13 for 102 weeks (maintenance group) and for those who received RP for 54 weeks and then switched to CT-P13 (switch group). Results Overall, 302 of 455 patients who completed the PLANETRA study enrolled into the extension. Of these, 158 had received CT-P13 (maintenance group) and 144 RP (switch group). Response rates at week 102 for maintenance versus switch groups, respectively, were 71.7% vs 71.8% for ACR20, 48.0% vs 51.4% for ACR50 and 24.3% vs 26.1% for ACR70. The proportion of patients with antidrug antibodies was comparable between groups (week 102: 40.3% vs 44.8%, respectively). Treatment-emergent adverse events occurred in similar proportions of patients in the two groups during the extension study (53.5% and 53.8%, respectively). Conclusions Comparable efficacy and tolerability were observed in patients who switched from RP to its biosimilar CT-P13 for an additional year and in those who had long-term CT-P13 treatment for 2 years. Trial registration number NCT01571219; Results. PMID:27130908

Evaluation of the Cross-reactivity of Antidrug Antibodies to CT-P13 and Infliximab Reference Product (Remicade): An Analysis Using Immunoassays Tagged with Both Agents.

PubMed

Reinisch, Walter; Jahnsen, Jørgen; Schreiber, Stefan; Danese, Silvio; Panés, Julián; Balsa, Alejandro; Park, Won; Kim, JiSoo; Lee, Jee Un; Yoo, Dae Hyun

2017-06-01

During two pivotal clinical trials of the infliximab biosimilar CT-P13 (PLANETAS and PLANETRA), antidrug antibodies (ADAs) and neutralising antibodies (NAbs) were detected in the sera of patients treated with CT-P13 and the reference product (RP; Remicade). The aim was to assess the comparability of Remicade- and CT-P13-tagged immunoassays for the detection of ADAs and NAbs using data from these trials, in order to determine the cross-reactivity of CT-P13 and RP ADAs. Sera from patients with rheumatoid arthritis and ankylosing spondylitis were analysed using an electrochemiluminescence (ECL) bridging assay or Gyros immunoassay, tagged with Remicade or CT-P13 at screening, weeks 14, 30 and 54, and the end of study visit. NAb titre was compared at screening and weeks 14 and 30. The proportion of cross-reactive samples was determined and an inter-rater agreement analysis performed to assess the concordance of results between assays. In PLANETAS, 93.1% (94/101) of RP ADA-positive samples and 93.0% (93/100) of RP NAb-positive samples cross-reacted with CT-P13; 99.0% (103/104) of CT-P13 ADA-positive and 98.0% (98/100) of CT-P13 NAb-positive samples cross-reacted with the RP. In PLANETRA, 94.7% (426/450) of RP ADA-positive samples and 94.3% (415/440) of RP NAb-positive samples cross-reacted with CT-P13, and 96.6% (458/474) of CT-P13 ADA-positive and 96.4% (452/469) of CT-P13 NAb-positive samples cross-reacted with the RP. In both studies, there was strong agreement in outcome between assays at all post-screening time points (PLANETAS: Cohen's κ 0.89-0.98 for ADA, 0.86-0.98 for NAb; PLANETRA: 0.92-0.94 for both ADA and NAb, all p < 0.001). Significant concordance between assays was observed for NAb titre at weeks 14 and 30 (PLANETAS: Spearman's ρ 0.73 and 0.74, respectively; PLANETRA: 0.61 and 0.72, respectively; all p < 0.001). This study has demonstrated that ADAs and NAbs against CT-P13 and RP are cross-reactive, indicating that CT-P13 and RP share immunodominant epitopes.

Activation and inhibition of CTP synthase from Trypanosoma brucei, the causative agent of African sleeping sickness.

PubMed

Steeves, Craig H; Bearne, Stephen L

2011-09-15

CTP Synthase from Trypanosoma brucei (TbCTPS) catalyzes the conversion of UTP to CTP and is a recognized target for the development of antiprotozoal agents. GTP activates glutamine-dependent CTP formation catalyzed by TbCTPS at concentrations below 0.2 mM, but inhibits this activity at concentrations above 0.2 mM. TbCTPS catalyzes ammonia-dependent CTP formation, which is inhibited by purine derivatives such as GTP, guanosine, caffeine, and uric acid with IC(50) values of 460, 380, 480, and 100 μM, respectively. These observations suggest that the purine ring may serve as a useful scaffold for the development of inhibitors of trypanosomal CTP synthase. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cochlin-tomoprotein (CTP) detection test identified perilymph leakage preoperatively in revision stapes surgery.

PubMed

Kataoka, Yuko; Ikezono, Tetsuo; Fukushima, Kunihiro; Yuen, Koji; Maeda, Yukihide; Sugaya, Akiko; Nishizaki, Kazunori

2013-08-01

Perilymphatic fistula (PLF) is defined as an abnormal leakage between perilymph from the labyrinth to the middle ear. Symptoms include hearing loss, tinnitus, and vertigo. The standard mode of PLF detection is intraoperative visualization of perilymph leakage and fistula, which ostensibly confirms the existence of PLF. Other possible methods of diagnosis include confirmation of pneumolabyrinth via diagnostic imaging. Recently, a cochlin-tomoprotein (CTP) detection test has been developed that allows definitive diagnosis of PLF-related hearing loss. We report the case of a 45-year-old man who presented with right-sided tinnitus, hearing loss, and dizziness 30 years after stapes surgery. Middle ear lavage was performed after myringotomy. A preoperative diagnosis of PLF was reached using the CTP detection test. Intraoperative observations included a necrotic long process of the incus, displaced wire piston, and fibrous tissue in the oval window. Perilymph leakage was not evident. The oval window was closed with fascia, and vertigo disappeared within 2 weeks postoperatively. When PLF is suspected after stapes surgery, the CTP detection test can be a useful, highly sensitive, and less invasive method for preoperative diagnosis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Personalized assessment of radiation risks from the one-stop-shop myocardial 256-slice CT examination.

PubMed

Perisinakis, Kostas; Seimenis, Ioannis; Tzedakis, Antonis; Pagonidis, Kostas; Papadakis, Antonios E; Damilakis, John

2013-10-15

This study provides data on the cumulative life attributable risk (LAR) of radiation-induced cancer from the combination of coronary CT angiography (CCTA), dynamic CT perfusion (CTP) and delayed enhancement (DE) CT scans, required for reliable risk-benefit analysis of the one-stop-shop CCTA + CTP + DECT cardiac examination. Monte Carlo simulation of the dynamic CTP and DECT exposures on 62 adult individuals was employed to determine radiation absorbed dose to exposed radiosensitive organs. Corresponding data for CCTA were derived using patient chest circumference and previously published data. Individual-specific LARs of cancer were estimated using organ/tissue-specific radiogenic cancer risk factors. Total LAR from CCTA + CTP + DECT scans' sequence were estimated and compared to nominal intrinsic risk of cancer. The main contribution, up to 80%, to cumulative radiation burden from CCTA + CTP + DECT scan-sequence was found to originate from the CTP scan. The total LAR from CCTA + CTP + DECT for females was found 4-6 times higher, compared to males. The mean cumulative risk of radiogenic cancer associated with the complete CCTA + CTP + DECT scan sequence was found to marginally increase the intrinsic risk for cancer induction by less than 0.6% and 0.1% for females and males, respectively. The radiation risk from the 256-slice CCTA + CTP + DECT scan sequence may be considered low and should not constitute an obstacle for the clinical endorsement of the one-stop-shop cardiac CT examination, given that its clinical value has been well verified. Nevertheless, every effort should be made towards optimization of the dynamic CTP component which is the main contributor to patient radiation burden. © 2013.

Are dispensaries indispensable? Patient experiences of access to cannabis from medical cannabis dispensaries in Canada.

PubMed

Capler, Rielle; Walsh, Zach; Crosby, Kim; Belle-Isle, Lynne; Holtzman, Susan; Lucas, Philippe; Callaway, Robert

2017-09-01

In 2001, Canada established a federal program for cannabis for therapeutic purposes (CTP). Medical cannabis dispensaries (dispensaries) are widely accessed as a source of CTP despite storefront sales of cannabis being illegal. The discrepancy between legal status and social practice has fuelled active debate regarding the role of dispensaries. The present study aims to inform this debate by analysing CTP user experiences with different CTP sources, and comparing dispensary users to those accessing CTP from other sources. We compared sociodemographic characteristics, health related factors and patterns of cannabis use of 445 respondents, 215 who accessed CTP from dispensaries with 230 who accessed other sources. We compared patients' ratings of CTP sources (dispensaries, Health Canada's supplier, self-production, other producer, friend or acquaintance, street dealer) for quality and availability of product, safety and efficiency of access, cost, and feeling respected while accessing. Patients using dispensaries were older, more likely to have arthritis and HIV/AIDS, and less likely to have mental health conditions than those not using dispensaries. Those accessing dispensaries used larger quantities of cannabis, placed greater value on access to specific strains, and were more likely to have legal authorization for CTP. Dispensaries were rated equally to or more favourably than other sources of CTP for quality, safety, availability, efficiency and feeling respected, and less favourably than self-production and other producer for cost. Given the high endorsement of dispensaries by patients, future regulations should consider including dispensaries as a source of CTP and address known barriers to access such as cost and health care provider support. Further research should assess the impact of the addition of licensed producers on the role and perceived value of dispensaries within the Canadian medical cannabis system. Copyright © 2017 Elsevier B.V. All rights reserved.

Noise characteristics of CT perfusion imaging: how does noise propagate from source images to final perfusion maps?

NASA Astrophysics Data System (ADS)

Li, Ke; Chen, Guang-Hong

2016-03-01

Cerebral CT perfusion (CTP) imaging is playing an important role in the diagnosis and treatment of acute ischemic strokes. Meanwhile, the reliability of CTP-based ischemic lesion detection has been challenged due to the noisy appearance and low signal-to-noise ratio of CTP maps. To reduce noise and improve image quality, a rigorous study on the noise transfer properties of CTP systems is highly desirable to provide the needed scientific guidance. This paper concerns how noise in the CTP source images propagates to the final CTP maps. Both theoretical deviations and subsequent validation experiments demonstrated that, the noise level of background frames plays a dominant role in the noise of the cerebral blood volume (CBV) maps. This is in direct contradiction with the general belief that noise of non-background image frames is of greater importance in CTP imaging. The study found that when radiation doses delivered to the background frames and to all non-background frames are equal, lowest noise variance is achieved in the final CBV maps. This novel equality condition provides a practical means to optimize radiation dose delivery in CTP data acquisition: radiation exposures should be modulated between background frames and non-background frames so that the above equality condition is satisïnAed. For several typical CTP acquisition protocols, numerical simulations and in vivo canine experiment demonstrated that noise of CBV can be effectively reduced using the proposed exposure modulation method.

Perceptions of cannabis as a stigmatized medicine: a qualitative descriptive study

PubMed Central

2013-01-01

Background Despite its increasing prevalence and acceptance among the general public, cannabis use continues to be viewed as an aberrant activity in many contexts. However, little is known about how stigma associated with cannabis use affects individuals who use cannabis for therapeutic purposes (CTP) and what strategies these individuals employ to manage associated stigma. The aim of this Canadian study was to describe users’ perceptions of and responses to the stigma attached to using CTP. Methods Twenty-three individuals who were using CTP for a range of health problems took part in semi-structured interviews. Transcribed data were analyzed using an inductive approach and comparative strategies to explore participants’ perceptions of CTP and identify themes. Results Participant experiences of stigma were related to negative views of cannabis as a recreational drug, the current criminal sanctions associated with cannabis use, and using cannabis in the context of stigmatizing vulnerability (related to existing illness and disability). Strategies for managing the resulting stigma of using CTP included: keeping CTP ‘undercover’; educating those who did not approve of or understand CTP use; and using cannabis responsibly. Conclusions Understanding how individuals perceive and respond to stigma can inform the development of strategies aimed at reducing stigma associated with the use of CTP and thereby address barriers faced by those using this medicine. PMID:23414118

A benchmarking tool to evaluate computer tomography perfusion infarct core predictions against a DWI standard.

PubMed

Cereda, Carlo W; Christensen, Søren; Campbell, Bruce Cv; Mishra, Nishant K; Mlynash, Michael; Levi, Christopher; Straka, Matus; Wintermark, Max; Bammer, Roland; Albers, Gregory W; Parsons, Mark W; Lansberg, Maarten G

2016-10-01

Differences in research methodology have hampered the optimization of Computer Tomography Perfusion (CTP) for identification of the ischemic core. We aim to optimize CTP core identification using a novel benchmarking tool. The benchmarking tool consists of an imaging library and a statistical analysis algorithm to evaluate the performance of CTP. The tool was used to optimize and evaluate an in-house developed CTP-software algorithm. Imaging data of 103 acute stroke patients were included in the benchmarking tool. Median time from stroke onset to CT was 185 min (IQR 180-238), and the median time between completion of CT and start of MRI was 36 min (IQR 25-79). Volumetric accuracy of the CTP-ROIs was optimal at an rCBF threshold of <38%; at this threshold, the mean difference was 0.3 ml (SD 19.8 ml), the mean absolute difference was 14.3 (SD 13.7) ml, and CTP was 67% sensitive and 87% specific for identification of DWI positive tissue voxels. The benchmarking tool can play an important role in optimizing CTP software as it provides investigators with a novel method to directly compare the performance of alternative CTP software packages. © The Author(s) 2015.

Tetrameric Ctp1 coordinates DNA binding and DNA bridging in DNA double-strand-break repair

DOE PAGES

Andres, Sara N.; Appel, C. Denise; Westmoreland, James W.; ...

2015-01-12

Ctp1 (also known as CtIP or Sae2) collaborates with Mre11-Rad50-Nbs1 to initiate repair of DNA double-strand breaks (DSBs), but its functions remain enigmatic. In this paper, we report that tetrameric Schizosaccharomyces pombe Ctp1 contains multivalent DNA-binding and DNA-bridging activities. Through structural and biophysical analyses of the Ctp1 tetramer, we define the salient features of Ctp1 architecture: an N-terminal interlocking tetrameric helical dimer-of-dimers (THDD) domain and a central intrinsically disordered region (IDR) linked to C-terminal 'RHR' DNA-interaction motifs. The THDD, IDR and RHR are required for Ctp1 DNA-bridging activity in vitro, and both the THDD and RHR are required for efficientmore » DSB repair in S. pombe. Finally, our results establish non-nucleolytic roles of Ctp1 in binding and coordination of DSB-repair intermediates and suggest that ablation of human CtIP DNA binding by truncating mutations underlie the CtIP-linked Seckel and Jawad syndromes.« less

Inventory of File WAFS_blended_2014102006f06.grib2

Science.gov Websites

) [%] 004 700 mb CTP 6 hour fcst In-Cloud Turbulence [%] spatial ave,code table 4.15=3,#points=1 005 700 mb CTP 6 hour fcst In-Cloud Turbulence [%] spatial max,code table 4.15=3,#points=1 006 600 mb CTP 6 hour fcst In-Cloud Turbulence [%] spatial ave,code table 4.15=3,#points=1 007 600 mb CTP 6 hour fcst In

Ischemic Volume and Neurological Deficit: Correlation of Computed Tomography Perfusion with the National Institutes of Health Stroke Scale Score in Acute Ischemic Stroke.

PubMed

Furlanis, Giovanni; Ajčević, Miloš; Stragapede, Lara; Lugnan, Carlo; Ridolfi, Mariana; Caruso, Paola; Naccarato, Marcello; Ukmar, Maja; Manganotti, Paolo

2018-04-30

The National Institutes of Health Stroke Scale (NIHSS) is the most adopted stroke patients' evaluation tool in emergency settings to assess the severity of stroke and to determine the patients' eligibility for specific treatments. Computed tomography perfusion (CTP) is crucial to identify salvageable tissue that can benefit from the reperfusion treatment. The aim of this study is to identify the relation between the NIHSS scores and the hypoperfused volumes evaluated by CTP in patients with hyperacute ischemic stroke. This retrospective study was conducted on 105 patients with ischemic stroke who underwent NIHSS assessment and CTP in the hyperacute phase. Hypoperfused volume was evaluated by CTP maps processed with semi-automatic algorithm. An analysis was conducted to determine the degree of correlation between the NIHSS scores and the ischemic lesion volumes and to investigate the relation between the anterior and the posterior circulation strokes, as well as between the right and the left hemispheric strokes. A significant correlation was found between ischemic volume and NIHSS score at baseline (r = .82; P < .0001) in the entire cohort. A high NIHSS-volume correlation was identified in the anterior circulation stroke (r = .76; P < .0001); whereas, it was nonsignificant in the posterior circulation stroke. NIHSS score and volume correlated for the left and the right hemispheric strokes (r = .83 and .81; P < .0001), showing a slightly higher slope in the left. This study showed a strong correlation between the baseline NIHSS score and the ischemic volume estimated by CTP. We confirmed that NIHSS is a reliable predictor of perfusion deficits in acute ischemic stroke. CTP allows fast imaging assessment in the hyperacute phase. The results highlight the importance of these diagnostic tools in the assessment of stroke severity and in acute decision-making. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Preparation of Chitin-PLA laminated composite for implantable application.

PubMed

Nasrin, Romana; Biswas, Shanta; Rashid, Taslim Ur; Afrin, Sanjida; Jahan, Rumana Akhter; Haque, Papia; Rahman, Mohammed Mizanur

2017-12-01

The present study explores the possibilities of using locally available inexpensive waste prawn shell derived chitin reinforced and bioabsorbable polylactic acid (PLA) laminated composites to develop new materials with excellent mechanical and thermal properties for implantable application such as in bone or dental implant. Chitin at different concentration (1-20% of PLA) reinforced PLA films (CTP) were fabricated by solvent casting process and laminated chitin-PLA composites (LCTP) were prepared by laminating PLA film (obtained by hot press method) with CTP also by hot press method at 160 °C. The effect of variation of chitin concentration on the resulting laminated composite's behavior was investigated. The detailed physico-mechanical, surface morphology and thermal were assessed with different characterization technique such as FT-IR, XRD, SEM and TGA. The FTIR spectra showed the characteristic peaks for chitin and PLA in the composites. SEM images showed an excellent dispersion of chitin in the films and composites. Thermogravimetric analysis (TGA) showed that the complete degradation of chitin, PLA film, 5% chitin reinforced PLA film (CTP2) and LCTP are 98%, 95%, 87% and 98% respectively at temperature of 500 °C. The tensile strength of the LCTP was found 25.09 MPa which is significantly higher than pure PLA film (18.55 MPa) and CTP2 film (8.83 MPa). After lamination of pure PLA and CTP2 film, the composite (LCTP) yielded 0.265-1.061% water absorption from 30 min to 24 h immerse in water that is much lower than PLA and CTP. The increased mechanical properties of the laminated films with the increase of chitin content indicated good dispersion of chitin into PLA and strong interfacial actions between the polymer and chitin. The improvement of mechanical properties and the results of antimicrobial and cytotoxicity of the composites also evaluated and revealed the composite would be a suitable candidate for implant application in biomedical sector.

A Novel P1B-type Mn2+-transporting ATPase Is Required for Secreted Protein Metallation in Mycobacteria*

PubMed Central

Padilla-Benavides, Teresita; Long, Jarukit E.; Raimunda, Daniel; Sassetti, Christopher M.; Argüello, José M.

2013-01-01

Transition metals are central for bacterial virulence and host defense. P1B-ATPases are responsible for cytoplasmic metal efflux and play roles either in limiting cytosolic metal concentrations or in the maturation of secreted metalloproteins. The P1B-ATPase, CtpC, is required for Mycobacterium tuberculosis survival in a mouse model (Sassetti, C. M., and Rubin, E. J. (2003) Genetic requirements for mycobacterial survival during infection. Proc. Natl. Acad. Sci. U.S.A. 100, 12989–12994). CtpC prevents Zn2+ toxicity, suggesting a role in Zn2+ export from the cytosol (Botella, H., Peyron, P., Levillain, F., Poincloux, R., Poquet, Y., Brandli, I., Wang, C., Tailleux, L., Tilleul, S., Charriere, G. M., Waddell, S. J., Foti, M., Lugo-Villarino, G., Gao, Q., Maridonneau-Parini, I., Butcher, P. D., Castagnoli, P. R., Gicquel, B., de Chastellièr, C., and Neyrolles, O. (2011) Mycobacterial P1-type ATPases mediate resistance to zinc poisoning in human macrophages. Cell Host Microbe 10, 248–259). However, key metal-coordinating residues and the overall structure of CtpC are distinct from Zn2+-ATPases. We found that isolated CtpC has metal-dependent ATPase activity with a strong preference for Mn2+ over Zn2+. In vivo, CtpC is unable to complement Escherichia coli lacking a functional Zn2+-ATPase. Deletion of M. tuberculosis or Mycobacterium smegmatis ctpC leads to cytosolic Mn2+ accumulation but no alterations in other metals levels. Whereas ctpC-deficient M. tuberculosis is sensitive to extracellular Zn2+, the M. smegmatis mutant is not. Both ctpC mutants are sensitive to oxidative stress, which might explain the Zn2+-sensitive phenotype of the M. tuberculosis ctpC mutant. CtpC is a high affinity/slow turnover ATPase, suggesting a role in protein metallation. Consistent with this hypothesis, mutation of CtpC leads to a decrease of Mn2+ bound to secreted proteins and of the activity of secreted Fe/Mn-superoxide dismutase, particularly in M. smegmatis. Alterations in the assembly of metalloenzymes involved in redox stress response might explain the sensitivity of M. tuberculosis ctpC mutants to oxidative stress and growth and persistence defects in mice infection models. PMID:23482562

Reference materials for cellular therapeutics.

PubMed

Bravery, Christopher A; French, Anna

2014-09-01

The development of cellular therapeutics (CTP) takes place over many years, and, where successful, the developer will anticipate the product to be in clinical use for decades. Successful demonstration of manufacturing and quality consistency is dependent on the use of complex analytical methods; thus, the risk of process and method drift over time is high. The use of reference materials (RM) is an established scientific principle and as such also a regulatory requirement. The various uses of RM in the context of CTP manufacturing and quality are discussed, along with why they are needed for living cell products and the analytical methods applied to them. Relatively few consensus RM exist that are suitable for even common methods used by CTP developers, such as flow cytometry. Others have also identified this need and made proposals; however, great care will be needed to ensure any consensus RM that result are fit for purpose. Such consensus RM probably will need to be applied to specific standardized methods, and the idea that a single RM can have wide applicability is challenged. Written standards, including standardized methods, together with appropriate measurement RM are probably the most appropriate way to define specific starting cell types. The characteristics of a specific CTP will to some degree deviate from those of the starting cells; consequently, a product RM remains the best solution where feasible. Each CTP developer must consider how and what types of RM should be used to ensure the reliability of their own analytical measurements. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

A review of the literature analyzing benefits and concerns of infliximab biosimilar CT-P13 for the treatment of rheumatologic diseases: focus on interchangeability

PubMed Central

Becciolini, Andrea; Raimondo, Maria Gabriella; Crotti, Chiara; Agape, Elena; Biggioggero, Martina; Favalli, Ennio Giulio

2017-01-01

The introduction of biological agents drastically changed the treatment paradigm of inflammatory arthritides, ameliorating the natural history of the diseases but concomitantly increasing the drug costs due to the manufacturing process. On this concern, biosimilar drugs may represent a valid option for reducing this elevated cost and increasing the availability of these highly effective treatments. Recently, CT-P13, the first biosimilar of infliximab, has been approved with the same indications established for the reference product (RP), and its daily use is progressively increasing. However, the experience with biosimilar drugs in the field of rheumatology is still limited, raising potential doubts and concerns on their correct management in real-life settings. Comparability analysis between CT-P13 and its RP was evaluated in equivalence randomized controlled trials (RCTs) – PLANETRA and PLANETAS – performed on patients with rheumatoid arthritis and axial spondylitis, respectively. CT-P13 and RP showed similar profile in terms of quality, biological activity, safety, immunogenicity, and efficacy. However, the interchangeability between infliximab RP and its biosimilar still represents the most challenging issue because of a lack of a long-lasting experience. To date, reassuring preliminary data on this topic were reported in open-label extensions of PLANETRA and PLANETAS RCTs and in ongoing real-life observational studies. These findings, taken all together, significantly affect the landscape of biosimilar regulatory pathways and strongly support CT-P13 introduction as a great opportunity for expanding the accessibility to these very effective and high-cost therapies. PMID:28721016

A review of the literature analyzing benefits and concerns of infliximab biosimilar CT-P13 for the treatment of rheumatologic diseases: focus on interchangeability.

PubMed

Becciolini, Andrea; Raimondo, Maria Gabriella; Crotti, Chiara; Agape, Elena; Biggioggero, Martina; Favalli, Ennio Giulio

2017-01-01

The introduction of biological agents drastically changed the treatment paradigm of inflammatory arthritides, ameliorating the natural history of the diseases but concomitantly increasing the drug costs due to the manufacturing process. On this concern, biosimilar drugs may represent a valid option for reducing this elevated cost and increasing the availability of these highly effective treatments. Recently, CT-P13, the first biosimilar of infliximab, has been approved with the same indications established for the reference product (RP), and its daily use is progressively increasing. However, the experience with biosimilar drugs in the field of rheumatology is still limited, raising potential doubts and concerns on their correct management in real-life settings. Comparability analysis between CT-P13 and its RP was evaluated in equivalence randomized controlled trials (RCTs) - PLANETRA and PLANETAS - performed on patients with rheumatoid arthritis and axial spondylitis, respectively. CT-P13 and RP showed similar profile in terms of quality, biological activity, safety, immunogenicity, and efficacy. However, the interchangeability between infliximab RP and its biosimilar still represents the most challenging issue because of a lack of a long-lasting experience. To date, reassuring preliminary data on this topic were reported in open-label extensions of PLANETRA and PLANETAS RCTs and in ongoing real-life observational studies. These findings, taken all together, significantly affect the landscape of biosimilar regulatory pathways and strongly support CT-P13 introduction as a great opportunity for expanding the accessibility to these very effective and high-cost therapies.

Automated prediction of tissue outcome after acute ischemic stroke in computed tomography perfusion images

NASA Astrophysics Data System (ADS)

Vos, Pieter C.; Bennink, Edwin; de Jong, Hugo; Velthuis, Birgitta K.; Viergever, Max A.; Dankbaar, Jan Willem

2015-03-01

Assessment of the extent of cerebral damage on admission in patients with acute ischemic stroke could play an important role in treatment decision making. Computed tomography perfusion (CTP) imaging can be used to determine the extent of damage. However, clinical application is hindered by differences among vendors and used methodology. As a result, threshold based methods and visual assessment of CTP images has not yet shown to be useful in treatment decision making and predicting clinical outcome. Preliminary results in MR studies have shown the benefit of using supervised classifiers for predicting tissue outcome, but this has not been demonstrated for CTP. We present a novel method for the automatic prediction of tissue outcome by combining multi-parametric CTP images into a tissue outcome probability map. A supervised classification scheme was developed to extract absolute and relative perfusion values from processed CTP images that are summarized by a trained classifier into a likelihood of infarction. Training was performed using follow-up CT scans of 20 acute stroke patients with complete recanalization of the vessel that was occluded on admission. Infarcted regions were annotated by expert neuroradiologists. Multiple classifiers were evaluated in a leave-one-patient-out strategy for their discriminating performance using receiver operating characteristic (ROC) statistics. Results showed that a RandomForest classifier performed optimally with an area under the ROC of 0.90 for discriminating infarct tissue. The obtained results are an improvement over existing thresholding methods and are in line with results found in literature where MR perfusion was used.

Gemcitabine diphosphate choline is a major metabolite linked to the Kennedy pathway in pancreatic cancer models in vivo.

PubMed

Bapiro, T E; Frese, K K; Courtin, A; Bramhall, J L; Madhu, B; Cook, N; Neesse, A; Griffiths, J R; Tuveson, D A; Jodrell, D I; Richards, F M

2014-07-15

The modest benefits of gemcitabine (dFdC) therapy in patients with pancreatic ductal adenocarcinoma (PDAC) are well documented, with drug delivery and metabolic lability cited as important contributing factors. We have used a mouse model of PDAC: KRAS(G12D); p53(R172H); pdx-Cre (KPC) that recapitulates the human disease to study dFdC intra-tumoural metabolism. LC-MS/MS and NMR were used to measure drug and physiological analytes. Cytotoxicity was assessed by the Sulphorhodamine B assay. In KPC tumour tissue, we identified a new, Kennedy pathway-linked dFdC metabolite (gemcitabine diphosphate choline (GdPC)) present at equimolar amounts to its precursor, the accepted active metabolite gemcitabine triphosphate (dFdCTP). Utilising additional subcutaneous PDAC tumour models, we demonstrated an inverse correlation between GdPC/dFdCTP ratios and cytidine triphosphate (CTP). In tumour homogenates in vitro, CTP inhibited GdPC formation from dFdCTP, indicating competition between CTP and dFdCTP for CTP:phosphocholine cytidylyltransferase (CCT). As the structure of GdPC precludes entry into cells, potential cytotoxicity was assessed by stimulating CCT activity using linoleate in KPC cells in vitro, leading to increased GdPC concentration and synergistic growth inhibition after dFdC addition. GdPC is an important element of the intra-tumoural dFdC metabolic pathway in vivo.

Comparable Immune Function Inhibition by the Infliximab Biosimilar CT-P13: Implications for Treatment of Inflammatory Bowel Disease.

PubMed

Lim, Ki Jung; Lee, So Jung; Kim, Sunghwan; Lee, Su Yeon; Lee, Min Seob; Park, Yoon A; Choi, Eun Jin; Lee, Eun Beom; Jun, Hwang Keun; Cho, Jong Moon; Lee, SooYoung; Kwon, Ki Sung; Lim, Byung Pil; Jeon, Myung-Shin; Shin, Eui Cheol; Choi, Yong Sung; Fudim, Ella; Picard, Orit; Yavzori, Miri; Ben-Horin, Shomron; Chang, Shin Jae

2017-05-01

CT-P13 is the first biosimilar monoclonal antibody to infliximab, and was recently approved in the European Union, Japan, Korea, and USA for all six indications of infliximab. However, studies directly assessing the biologic activity of CT-P13 versus inflximab in the context of inflammatory bowel disease [IBD] are still scanty. In the present study, we aimed to compare the biological activities of CT-P13 and infliximab with specific focus on intestinal cells so as to gain insight into the potential biosimilarity of these two agents for treatment of IBD. CT-P13 and infliximab were investigated and compared by in vitro experiments for their neutralisation ability of soluble tumour necrosis factor alpha [sTNFα] and membrane-bound tumour necrosis factor alpha [mTNFα], suppression of cytokine release by reverse signalling, induction of regulatory macrophages and wound healing, and antibody-dependent cell cytotoxicity [ADCC]. CT-P13 showed similar biological activities to infliximab as gauged by neutralisation of soluble TNFα, as well as blockade of apoptosis and suppression of pro-inflammatory cytokines in intestinal Caco-2 cells. Infliximab and CT-P13 equally induced apoptosis and outside-to-inside signals through transmembrane TNFα [tmTNFα]. Moreover, regulatory macrophage induction and ensuing wound healing were similarly exerted by CT-P13 and infliximab. However, neither CT-P13 nor infliximab exerted any significant ADCC of ex vivo-stimulated peripheral blood monocytes or lamina propria mononuclear cells from IBD patients. These findings indicate that CT-P13 and infliximab exert highly similar biological activities in intestinal cells, and further support a mechanistic comparability of these two drugs in the treatment of IBD. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study

PubMed Central

Park, Won; Yoo, Dae Hyun; Miranda, Pedro; Brzosko, Marek; Wiland, Piotr; Gutierrez-Ureña, Sergio; Mikazane, Helena; Lee, Yeon-Ah; Smiyan, Svitlana; Lim, Mie-Jin; Kadinov, Vladimir; Abud-Mendoza, Carlos; Kim, HoUng; Lee, Sang Joon; Bae, YunJu; Kim, SuYeon; Braun, Jürgen

2017-01-01

Objectives To investigate the efficacy and safety of switching from infliximab reference product (RP) to its biosimilar or maintaining biosimilar treatment in patients with ankylosing spondylitis (AS). Methods This open-label extension study recruited patients with AS who completed a 54-week, randomised controlled study comparing CT-P13 with RP (PLANETAS). CT-P13 (5 mg/kg) was administered intravenously every 8 weeks from week 62 to week 102. Efficacy end points included the proportion of patients achieving Assessment of SpondyloArthritis international Society (ASAS)20. Antidrug antibodies (ADAs) were measured using an electrochemiluminescent method. Data were analysed for patients treated with CT-P13 in the main PLANETAS study and the extension (maintenance group) and those who were switched to CT-P13 during the extension study (switch group). Results Overall, 174 (82.9%) of 210 patients who completed the first 54 weeks of PLANETAS and agreed to participate in the extension were enrolled. Among these, 88 were maintained on CT-P13 and 86 were switched to CT-P13 from RP. In these maintenance and switch groups, respectively, ASAS20 response rates at week 102 were 80.7% and 76.9%. ASAS40 and ASAS partial remission were also similar between groups. ADA positivity rates were comparable (week 102: 23.3% vs 27.4%). Adverse events led to treatment discontinuation during the extension study in 3 (3.3%) and 4 (4.8%) patients, respectively. Conclusions This is the first study to show that switching from RP to its biosimilar CT-P13 is possible without negative effects on safety or efficacy in patients with AS. In the maintenance group, CT-P13 was effective and well tolerated over 2 years of treatment. Trial registration number NCT01571206; Results. PMID:27117698

Diagnostic accuracy of semi-automatic quantitative metrics as an alternative to expert reading of CT myocardial perfusion in the CORE320 study.

PubMed

Ostovaneh, Mohammad R; Vavere, Andrea L; Mehra, Vishal C; Kofoed, Klaus F; Matheson, Matthew B; Arbab-Zadeh, Armin; Fujisawa, Yasuko; Schuijf, Joanne D; Rochitte, Carlos E; Scholte, Arthur J; Kitagawa, Kakuya; Dewey, Marc; Cox, Christopher; DiCarli, Marcelo F; George, Richard T; Lima, Joao A C

To determine the diagnostic accuracy of semi-automatic quantitative metrics compared to expert reading for interpretation of computed tomography perfusion (CTP) imaging. The CORE320 multicenter diagnostic accuracy clinical study enrolled patients between 45 and 85 years of age who were clinically referred for invasive coronary angiography (ICA). Computed tomography angiography (CTA), CTP, single photon emission computed tomography (SPECT), and ICA images were interpreted manually in blinded core laboratories by two experienced readers. Additionally, eight quantitative CTP metrics as continuous values were computed semi-automatically from myocardial and blood attenuation and were combined using logistic regression to derive a final quantitative CTP metric score. For the reference standard, hemodynamically significant coronary artery disease (CAD) was defined as a quantitative ICA stenosis of 50% or greater and a corresponding perfusion defect by SPECT. Diagnostic accuracy was determined by area under the receiver operating characteristic curve (AUC). Of the total 377 included patients, 66% were male, median age was 62 (IQR: 56, 68) years, and 27% had prior myocardial infarction. In patient based analysis, the AUC (95% CI) for combined CTA-CTP expert reading and combined CTA-CTP semi-automatic quantitative metrics was 0.87(0.84-0.91) and 0.86 (0.83-0.9), respectively. In vessel based analyses the AUC's were 0.85 (0.82-0.88) and 0.84 (0.81-0.87), respectively. No significant difference in AUC was found between combined CTA-CTP expert reading and CTA-CTP semi-automatic quantitative metrics in patient based or vessel based analyses(p > 0.05 for all). Combined CTA-CTP semi-automatic quantitative metrics is as accurate as CTA-CTP expert reading to detect hemodynamically significant CAD. Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Identification and Characterization of the Nuclear Isoform of Drosophila melanogaster CTP:Phosphocholine Cytidylyltransferase

USDA-ARS?s Scientific Manuscript database

CTP:phosphocholine cytidylyltransferase (CCT) catalyzes the conversion of phosphocholine and cytidine 5'-triphosphate (CTP) to CDP-choline for the eventual synthesis of phosphatidylcholine (PC). The enzyme is regulated by reversible association with cellular membranes, with the rate of catalysis in...

Gemcitabine diphosphate choline is a major metabolite linked to the Kennedy pathway in pancreatic cancer models in vivo

PubMed Central

Bapiro, T E; Frese, K K; Courtin, A; Bramhall, J L; Madhu, B; Cook, N; Neesse, A; Griffiths, J R; Tuveson, D A; Jodrell, D I; Richards, F M

2014-01-01

Background: The modest benefits of gemcitabine (dFdC) therapy in patients with pancreatic ductal adenocarcinoma (PDAC) are well documented, with drug delivery and metabolic lability cited as important contributing factors. We have used a mouse model of PDAC: KRASG12D; p53R172H; pdx-Cre (KPC) that recapitulates the human disease to study dFdC intra-tumoural metabolism. Methods: LC-MS/MS and NMR were used to measure drug and physiological analytes. Cytotoxicity was assessed by the Sulphorhodamine B assay. Results: In KPC tumour tissue, we identified a new, Kennedy pathway-linked dFdC metabolite (gemcitabine diphosphate choline (GdPC)) present at equimolar amounts to its precursor, the accepted active metabolite gemcitabine triphosphate (dFdCTP). Utilising additional subcutaneous PDAC tumour models, we demonstrated an inverse correlation between GdPC/dFdCTP ratios and cytidine triphosphate (CTP). In tumour homogenates in vitro, CTP inhibited GdPC formation from dFdCTP, indicating competition between CTP and dFdCTP for CTP:phosphocholine cytidylyltransferase (CCT). As the structure of GdPC precludes entry into cells, potential cytotoxicity was assessed by stimulating CCT activity using linoleate in KPC cells in vitro, leading to increased GdPC concentration and synergistic growth inhibition after dFdC addition. Conclusions: GdPC is an important element of the intra-tumoural dFdC metabolic pathway in vivo. PMID:24874484

Clinical Use of CT Perfusion For Diagnosis and Prediction of Lesion Growth in Acute Ischemic Stroke

PubMed Central

Huisa, Branko N; Neil, William P; Schrader, Ronald; Maya, Marcel; Pereira, Benedict; Bruce, Nhu T; Lyden, Patrick D

2012-01-01

Background and Purpose CT perfusion (CTP) mapping in research centers correlates well with diffusion weighted imaging (DWI) lesions and may accurately differentiate the infarct core from ischemic penumbra. The value of CTP in real-world clinical practice has not been fully established. We investigated the yield of CTP– derived cerebral blood volume (CBV) and mean transient time (MTT) for the detection of cerebral ischemia and ischemic penumbra in a sample of acute ischemic stroke (AIS) patients. Methods We studied 165 patients with initial clinical symptoms suggestive of AIS. All patients had an initial non-contrast head CT, CT Perfusion (CTP), CT angiogram (CTA) and follow up brain MRI. The obtained perfusion images were used for image processing. CBV, MTT and DWI lesion volumes were visually estimated and manually traced. Statistical analysis was done using R-2.14.and SAS 9.1. Results All normal DWI sequences had normal CBV and MTT studies (N=89). Seventy-three patients had acute DWI lesions. CBV was abnormal in 23.3% and MTT was abnormal in 42.5% of these patients. There was a high specificity (91.8%)but poor sensitivity (40.0%) for MTT maps predicting positive DWI. Spearman correlation was significant between MTT and DWI lesions (ρ=0.66, p>0.0001) only for abnormal MTT and DWI lesions>0cc. CBV lesions did not correlate with final DWI. Conclusions In real-world use, acute imaging with CTP did not predict stroke or DWI lesions with sufficient accuracy. Our findings argue against the use of CTP for screening AIS patients until real-world implementations match the accuracy reported from specialized research centers. PMID:23253533

Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study.

PubMed

Park, Won; Yoo, Dae Hyun; Miranda, Pedro; Brzosko, Marek; Wiland, Piotr; Gutierrez-Ureña, Sergio; Mikazane, Helena; Lee, Yeon-Ah; Smiyan, Svitlana; Lim, Mie-Jin; Kadinov, Vladimir; Abud-Mendoza, Carlos; Kim, HoUng; Lee, Sang Joon; Bae, YunJu; Kim, SuYeon; Braun, Jürgen

2017-02-01

To investigate the efficacy and safety of switching from infliximab reference product (RP) to its biosimilar or maintaining biosimilar treatment in patients with ankylosing spondylitis (AS). This open-label extension study recruited patients with AS who completed a 54-week, randomised controlled study comparing CT-P13 with RP (PLANETAS). CT-P13 (5 mg/kg) was administered intravenously every 8 weeks from week 62 to week 102. Efficacy end points included the proportion of patients achieving Assessment of SpondyloArthritis international Society (ASAS)20. Antidrug antibodies (ADAs) were measured using an electrochemiluminescent method. Data were analysed for patients treated with CT-P13 in the main PLANETAS study and the extension (maintenance group) and those who were switched to CT-P13 during the extension study (switch group). Overall, 174 (82.9%) of 210 patients who completed the first 54 weeks of PLANETAS and agreed to participate in the extension were enrolled. Among these, 88 were maintained on CT-P13 and 86 were switched to CT-P13 from RP. In these maintenance and switch groups, respectively, ASAS20 response rates at week 102 were 80.7% and 76.9%. ASAS40 and ASAS partial remission were also similar between groups. ADA positivity rates were comparable (week 102: 23.3% vs 27.4%). Adverse events led to treatment discontinuation during the extension study in 3 (3.3%) and 4 (4.8%) patients, respectively. This is the first study to show that switching from RP to its biosimilar CT-P13 is possible without negative effects on safety or efficacy in patients with AS. In the maintenance group, CT-P13 was effective and well tolerated over 2 years of treatment. NCT01571206; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Appropriate use of CT perfusion following aneurysmal subarachnoid hemorrhage: a Bayesian analysis approach.

PubMed

Killeen, R P; Gupta, A; Delaney, H; Johnson, C E; Tsiouris, A J; Comunale, J; Fink, M E; Mangat, H S; Segal, A Z; Mushlin, A I; Sanelli, P C

2014-03-01

In recent years CTP has been used as a complementary diagnostic tool in the evaluation of delayed cerebral ischemia and vasospasm. Our aim was to determine the test characteristics of CTP for detecting delayed cerebral ischemia and vasospasm in SAH, and then to apply Bayesian analysis to identify subgroups for its appropriate use. Our retrospective cohort comprised consecutive patients with SAH and CTP performed between days 6 and 8 following aneurysm rupture. Delayed cerebral ischemia was determined according to primary outcome measures of infarction and/or permanent neurologic deficits. Vasospasm was determined by using DSA. The test characteristics of CTP and its 95% CIs were calculated. Graphs of conditional probabilities were constructed by using Bayesian techniques. Local treatment thresholds (posttest probability of delayed cerebral ischemia needed to initiate induced hypertension, hypervolemia, and hemodilution or intra-arterial therapy) were determined via a survey of 6 independent neurologists. Ninety-seven patients with SAH were included in the study; 39% (38/97) developed delayed cerebral ischemia. Qualitative CTP deficits were seen in 49% (48/97), occurring in 84% (32/38) with delayed cerebral ischemia and 27% (16/59) without. The sensitivity, specificity, and positive and negative predictive values (95% CI) for CTP were 0.84 (0.73-0.96), 0.73 (0.62-0.84), 0.67 (0.51-0.79), and 0.88 (0.74-0.94), respectively. A subgroup of 57 patients underwent DSA; 63% (36/57) developed vasospasm. Qualitative CTP deficits were seen in 70% (40/57), occurring in 97% (35/36) with vasospasm and 23% (5/21) without. The sensitivity, specificity, and positive and negative predictive values (95% CI) for CTP were 0.97 (0.92-1.0), 0.76 (0.58-0.94), 0.88 (0.72-0.95), and 0.94 (0.69-0.99), respectively. Treatment thresholds were determined as 30% for induced hypertension, hypervolemia, and hemodilution and 70% for intra-arterial therapy. Positive CTP findings identify patients who should be carefully considered for induced hypertension, hypervolemia, and hemodilution and/or intra-arterial therapy while negative CTP findings are useful in guiding a no-treatment decision.

Pilot study comparing the Childhood Arthritis & Rheumatology Research Alliance (CARRA) systemic Juvenile Idiopathic Arthritis Consensus Treatment Plans.

PubMed

Kimura, Yukiko; Grevich, Sriharsha; Beukelman, Timothy; Morgan, Esi; Nigrovic, Peter A; Mieszkalski, Kelly; Graham, T Brent; Ibarra, Maria; Ilowite, Norman; Klein-Gitelman, Marisa; Onel, Karen; Prahalad, Sampath; Punaro, Marilynn; Ringold, Sarah; Toib, Dana; Van Mater, Heather; Weiss, Jennifer E; Weiss, Pamela F; Schanberg, Laura E

2017-04-11

To assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry. Untreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX] ± GC; IL1 inhibitor [IL1i] ± GC; IL6 inhibitor [IL6i] ± GC). The primary outcome of clinical inactive disease (CID) without current GC use was assessed at 9 months. clinicaltrials.gov NCT01697254; first registered 9/28/12 (retrospectively enrolled). Thirty patients were enrolled at 13 sites; eight patients were started on a non-biologic CTP (2 GC, 6 MTX) and 22 patients on a biologic CTP (12 IL1i, 10 IL6i) at disease onset. Demographic and disease features were similar between CTP groups. CTP choice appeared to segregate by site preference. CID off GC was achieved by 37% (11 of 30) including 11/22 (50%) starting a biologic CTP compared to 0/8 starting a non-biologic CTP (p = 0.014). There were four serious adverse events: two infections, one appendicitis and one macrophage activation syndrome. The CARRA systemic JIA CTP pilot study demonstrated successful implementation of CTPs using the CARRA registry infrastructure. Having demonstrated feasibility, a larger study using CTP response to better determine the relative effectiveness of treatments for new-onset systemic JIA is now underway.

Quantification of myocardial blood flow using dynamic 320-row multi-detector CT as compared with ¹⁵O-H₂O PET.

PubMed

Kikuchi, Yasuka; Oyama-Manabe, Noriko; Naya, Masanao; Manabe, Osamu; Tomiyama, Yuuki; Sasaki, Tsukasa; Katoh, Chietsugu; Kudo, Kohsuke; Tamaki, Nagara; Shirato, Hiroki

2014-07-01

This study introduces a method to calculate myocardium blood flow (MBF) and coronary flow reserve (CFR) using the relatively low-dose dynamic 320-row multi-detector computed tomography (MDCT), validates the method against (15)O-H₂O positron-emission tomography (PET) and assesses the CFRs of coronary artery disease (CAD) patients. Thirty-two subjects underwent both dynamic CT perfusion (CTP) and PET perfusion imaging at rest and during pharmacological stress. In 12 normal subjects (pilot group), the calculation method for MBF and CFR was established. In the other 13 normal subjects (validation group), MBF and CFR obtained by dynamic CTP and PET were compared. Finally, the CFRs obtained by dynamic CTP and PET were compared between the validation group and CAD patients (n = 7). Correlation between MBF of MDCT and PET was strong (r = 0.95, P < 0.0001). CFR showed good correlation between dynamic CTP and PET (r = 0.67, P = 0.0126). CFRCT in the CAD group (2.3 ± 0.8) was significantly lower than that in the validation group (5.2 ± 1.8) (P = 0.0011). We established a method for measuring MBF and CFR with the relatively low-dose dynamic MDCT. Lower CFR was well demonstrated in CAD patients by dynamic CTP. • MBF and CFR can be calculated using dynamic CTP with 320-row MDCT. • MBF and CFR showed good correlation between dynamic CTP and PET. • Lower CFR was well demonstrated in CAD patients by dynamic CTP.

Assessing the short- and long-term prognosis of patients with cirrhosis and acute variceal bleeding.

PubMed

Sempere, L; Palazón, J M; Sánchez-Payá, J; Pascual, S; de Madaria, E; Poveda, M J; Carnicer, F; Zapater, P; Pérez-Mateo, M

2009-04-01

to evaluate the efficacy of various indicators in predicting short- and long-term survival in patients with cirrhosis and acute variceal bleeding. prognostic indicators were calculated for a cohort of 201 cirrhotic patients with acute variceal bleeding hospitalized in our center, a third-level teaching hospital. The studied variables were: age, sex, etiology of cirrhosis, endoscopic findings, previous variceal bleeding episodes, human immunodeficiency virus (HIV) infection, hepatocellular carcinoma (HCC), infection during episode, and Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores within 24 hours of bleeding onset. Patients were followed up for at least 6 months until death, liver transplantation, or end of observation. median follow-up was 66.85 weeks (range 0-432.4). The 6-week, 3-month, 12-month and 36-month mortality rates were 22.9, 24.9, 34.3, and 39.8%, respectively. Age >= 65 years, presence of HCC, CTP score >=10, and MELD score >= 18 were the variables associated with mortality in the multivariate analysis. The accuracy of MELD scores as predictors of 6-week, 3-month, 12-month, and 36-month mortality was better than that of CTP scores (c-statistics: 6 week MELD 0.804, CTP 0.762; 3-month MELD 0.794, CTP 0.760; 12-month MELD 0.766, CTP 0.741; 36 month MELD 0.737, CTP 0.717). MELD and CTP scores together with age and a diagnosis of hepatocellular carcinoma are useful indicators to assess the short- and long-term prognosis of patients with acute variceal bleeding.

Phenotypes of gene disruptants in relation to a putative mitochondrial malate-citrate shuttle protein in citric acid-producing Aspergillus niger.

PubMed

Kirimura, Kohtaro; Kobayashi, Keiichi; Ueda, Yuka; Hattori, Takasumi

2016-09-01

The mitochondrial citrate transport protein (CTP) functions as a malate-citrate shuttle catalyzing the exchange of citrate plus a proton for malate between mitochondria and cytosol across the inner mitochondrial membrane in higher eukaryotic organisms. In this study, for functional analysis, we cloned the gene encoding putative CTP (ctpA) of citric acid-producing Aspergillus niger WU-2223L. The gene ctpA encodes a polypeptide consisting 296 amino acids conserved active residues required for citrate transport function. Only in early-log phase, the ctpA disruptant DCTPA-1 showed growth delay, and the amount of citric acid produced by strain DCTPA-1 was smaller than that by parental strain WU-2223L. These results indicate that the CTPA affects growth and thereby citric acid metabolism of A. niger changes, especially in early-log phase, but not citric acid-producing period. This is the first report showing that disruption of ctpA causes changes of phenotypes in relation to citric acid production in A. niger.

Accuracy of Computed Tomographic Perfusion in Diagnosis of Brain Death: A Prospective Cohort Study.

PubMed

Sawicki, Marcin; Sołek-Pastuszka, Joanna; Chamier-Ciemińska, Katarzyna; Walecka, Anna; Bohatyrewicz, Romuald

2018-05-04

BACKGROUND This study was designed to determine diagnostic accuracy of computed tomographic perfusion (CTP) compared to computed tomographic angiography (CTA) for the diagnosis of brain death (BD). MATERIAL AND METHODS Whole-brain CTP was performed in patients diagnosed with BD and in patients with devastating brain injury with preserved brainstem reflexes. CTA was derived from CTP datasets. Cerebral blood flow (CBF) and volume (CBV) were calculated in all brain regions. CTP findings were interpreted as confirming diagnosis of BD (positive) when CBF and CBV in all ROIs were below 10 mL/100 g/min and 1.0 mL/100 g, respectively. CTA findings were interpreted using a 4-point system. RESULTS Fifty brain-dead patients and 5 controls were included. In brain-dead patients, CTP results revealed CBF 0.00-9.98 mL/100 g/min and CBV 0.00-0.99 mL/100 g, and were thus interpreted as positive in all patients. CTA results suggested 7 negative cases, providing 86% sensitivity. In the non-brain-dead group, CTP results revealed CBF 2.37-37.59 mL/100 g/min and CBV 0.73-2.34 mL/100 g. The difference between values of CBF and CBV in the brain-dead and non-brain-dead groups was statistically significant (p=0.002 for CBF and p=0.001 for CBV). CTP findings in all non-brain-dead patients were interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTP in the diagnosis of BD. In all non-brain-dead patients, CTA revealed preserved intracranial filling and was interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTA in diagnosis of BD. CONCLUSIONS Whole-brain CTP seems to be a highly sensitive and specific method in diagnosis of BD.

A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study.

PubMed

Park, Won; Hrycaj, Pawel; Jeka, Slawomir; Kovalenko, Volodymyr; Lysenko, Grygorii; Miranda, Pedro; Mikazane, Helena; Gutierrez-Ureña, Sergio; Lim, MieJin; Lee, Yeon-Ah; Lee, Sang Joon; Kim, HoUng; Yoo, Dae Hyun; Braun, Jürgen

2013-10-01

To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS). Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed. Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0 μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively. The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30.

Evaluation of multifunctional imaging parameters in gastro-oesophageal cancer using F-18-FDG-PET/CT with integrated perfusion CT.

PubMed

Sah, Bert-Ram; Leissing, Christian A; Delso, Gaspar; Ter Voert, Edwin E; Krieg, Stefan; Leibl, Sebastian; Schneider, Paul M; Reiner, Cäcilia S; Hüllner, Martin W; Veit-Haibach, Patrick

2018-05-10

Positron emission tomography (PET) / computed tomography (CT) is among the most frequently used imaging modalities for initial staging of gastro-oesophageal (GE) cancer, whereas CT-perfusion (CTP) provides different multiparametric information. This proof of concept study compares CTP- and PET-parameters in patients with GE cancer to evaluate correlations and a possible prognostic value of a combined PET/CTP imaging procedure. A total of 31 patients with F-18-FDG-PET/CT and CTP studies were prospectively analysed. Patients had adenocarcinoma (n = 22) and oesophageal squamous cell carcinoma (SCC, n = 9). Imaging was performed before start of treatment. CTP parameters [blood flow (BF), blood volume (BV), mean transit time (MTT)] and metabolic parameters [(maximum and mean standardised uptake values and standard deviation (SUVmax, SUVmean, SUVsd), metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG)], as well as flow metabolic product [FMP (BF × SUVmax)] were determined and their relationship was compared. Additionally their association to clinical parameters (differentiation grading, staging, HER2-status, follow-up status) and to histopathological regression (post-neoadjuvant regression grading) was evaluated. Correlation between parameters of both modalities was significant between MTT and MTV (r = 0.375, p = 0.038); no other significant correlation was found. Patients with complete histopathological regression showed significantly lower BF and BV than patients with nearly complete or partial response. TLG and regression grading showed significant correlation with staging. All other quantitative parameters for CTP and PET data did not correlate significantly with histopathological regression grading, differentiation or staging. The combination of PET and CTP parameters (FMP) showed no significant prognostic value. Significant correlations were only found between MTT and MTV, which indicates a possible perfusional/metabolic coupling. Therefore, pre-therapeutic CTP and PET- parameters provide complementary information about the pre-therapeutic tumour status and are not interchangeable. Only CTP parameters might be able to predict complete histopathological regression. On the other hand, only PET parameters are correlated with staging.

Development of a realistic, dynamic digital brain phantom for CT perfusion validation

NASA Astrophysics Data System (ADS)

Divel, Sarah E.; Segars, W. Paul; Christensen, Soren; Wintermark, Max; Lansberg, Maarten G.; Pelc, Norbert J.

2016-03-01

Physicians rely on CT Perfusion (CTP) images and quantitative image data, including cerebral blood flow, cerebral blood volume, and bolus arrival delay, to diagnose and treat stroke patients. However, the quantification of these metrics may vary depending on the computational method used. Therefore, we have developed a dynamic and realistic digital brain phantom upon which CTP scans can be simulated based on a set of ground truth scenarios. Building upon the previously developed 4D extended cardiac-torso (XCAT) phantom containing a highly detailed brain model, this work consisted of expanding the intricate vasculature by semi-automatically segmenting existing MRA data and fitting nonuniform rational B-spline surfaces to the new vessels. Using time attenuation curves input by the user as reference, the contrast enhancement in the vessels changes dynamically. At each time point, the iodine concentration in the arteries and veins is calculated from the curves and the material composition of the blood changes to reflect the expected values. CatSim, a CT system simulator, generates simulated data sets of this dynamic digital phantom which can be further analyzed to validate CTP studies and post-processing methods. The development of this dynamic and realistic digital phantom provides a valuable resource with which current uncertainties and controversies surrounding the quantitative computations generated from CTP data can be examined and resolved.

Integrated controls and health monitoring for chemical transfer propulsion

NASA Technical Reports Server (NTRS)

Millis, Marc G.; Binder, Michael P.

1990-01-01

NASA is reviewing various propulsion technologies for exploring space. The requirements are examined for one enabling propulsion technology: Integrated Controls and Health Monitoring (ICHM) for Chemical Transfer Propulsion (CTP). Functional requirements for a CTP-ICHM system are proposed from tentative mission scenarios, vehicle configurations, CTP specifications, and technical feasibility. These CTP-ICHM requirements go beyond traditional reliable operation and emergency shutoff control to include: (1) enhanced mission flexibility; (2) continuously variable throttling; (3) tank-head start control; (4) automated prestart and post-shutoff engine check; (5) monitoring of space exposure degradation; and (6) product evolution flexibility. Technology development plans are also discussed.

Direct comparison of rest and adenosine stress myocardial perfusion CT with rest and stress SPECT

PubMed Central

Okada, David R.; Ghoshhajra, Brian B.; Blankstein, Ron; Rocha-Filho, Jose A.; Shturman, Leonid D.; Rogers, Ian S.; Bezerra, Hiram G.; Sarwar, Ammar; Gewirtz, Henry; Hoffmann, Udo; Mamuya, Wilfred S.; Brady, Thomas J.; Cury, Ricardo C.

2010-01-01

Introduction We have recently described a technique for assessing myocardial perfusion using adenosine-mediated stress imaging (CTP) with dual source computed tomography. SPECT myocardial perfusion imaging (SPECT-MPI) is a widely utilized and extensively validated method for assessing myocardial perfusion. The aim of this study was to determine the level of agreement between CTP and SPECT-MPI at rest and under stress on a per-segment, per-vessel, and per-patient basis. Methods Forty-seven consecutive patients underwent CTP and SPECT-MPI. Perfusion images were interpreted using the 17 segment AHA model and were scored on a 0 (normal) to 3 (abnormal) scale. Summed rest and stress scores were calculated for each vascular territory and patient by adding corresponding segmental scores. Results On a per-segment basis (n = 799), CTP and SPECT-MPI demonstrated excellent correlation: Goodman-Kruskall γ = .59 (P < .0001) for stress and .75 (P < .0001) for rest. On a per-vessel basis (n = 141), CTP and SPECT-MPI summed scores demonstrated good correlation: Pearson r = .56 (P < .0001) for stress and .66 (P < .0001) for rest. On a per-patient basis (n = 47), CTP and SPECT-MPI demonstrated good correlation: Pearson r = .60 (P < .0001) for stress and .76 (P < .0001) for rest. Conclusions CTP compares favorably with SPECT-MPI for detection, extent, and severity of myocardial perfusion defects at rest and stress. PMID:19936863

Comprehensive Study of Educational Technology Programs Authorized from 1989-1992. Volume IV: California Technology Project.

ERIC Educational Resources Information Center

Far West Lab. for Educational Research and Development, San Francisco, CA.

This report, the fourth in a series of six, describes the evaluative studies conducted during Phase II of the California Educational Technology Assessment Program, the California Technology Project (CTP), and the CTP Regional Consortia. The report begins with background information on the CTP, starting with the earlier statewide network of…

Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective, Combined Semi-Quantitative and Quantitative Assessment.

PubMed

Padroni, Marina; Bernardoni, Andrea; Tamborino, Carmine; Roversi, Gloria; Borrelli, Massimo; Saletti, Andrea; De Vito, Alessandro; Azzini, Cristiano; Borgatti, Luca; Marcello, Onofrio; d'Esterre, Christopher; Ceruti, Stefano; Casetta, Ilaria; Lee, Ting-Yim; Fainardi, Enrico

2016-01-01

The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned. 62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded. Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS ≤ 2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome. Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size.

Whole brain CT perfusion deficits using 320-detector-row CT scanner in TIA patients are associated with ABCD2 score.

PubMed

Mehta, Bijal K; Mustafa, Ghulam; McMurtray, Aaron; Masud, Mohammed W; Gunukula, Sameer K; Kamal, Haris; Kandel, Amit; Beltagy, Abdelrahman; Li, Ping

2014-01-01

Transient ischemic attacks (TIA) are cerebral ischemic events without infarction. The uses of CT perfusion (CTP) techniques such as cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT) and cerebral blood flow (CBF) provide real time data about ischemia. It has been shown that CTP changes occur in less sensitive CTP scanners in patients with TIA. Larger detector row CTP (whole brain perfusion studies) may show that CTP abnormalities are more prevalent than previously noted. It is also unclear if these changes are associated with TIA severity. To demonstrate that TIA patients are associated with perfusion deficits using whole brain 320-detector-row CT perfusion, and to determine an association between ABCD2 score and perfusion deficit using whole brain perfusion. We retrospectively reviewed all TIA patients for CTP deficits from 2008-2010. Perfusion imaging was reviewed at admission; and it was determined if a perfusion deficit was present along with vascular territory involved. Of 364 TIA patients, 62 patients had CTP deficits. The largest group of patients had MCA territory involved with 48 of 62 patients (77.42%). The most common perfusion abnormality was increased TTP with 46 patients (74.19%). The ABCD2 score was reviewed in association with perfusion deficit. Increased age >60, severe hypertension (>180/100 mmHg), patients with speech abnormalities, and duration of symptoms >10 min were associated with a perfusion deficit but history of diabetes or minimal/moderate hypertension (140/90-179/99 mmHg) was not. There was no association between motor deficit and perfusion abnormality. Perfusion deficits are found in TIA patients using whole brain CTP and associated with components of the ABCD2 score.

Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage.

PubMed

Malinova, Vesna; Dolatowski, Karoline; Schramm, Peter; Moerer, Onnen; Rohde, Veit; Mielke, Dorothee

2016-07-01

OBJECT This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI). METHODS Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)-measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated. RESULTS Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p < 0.0001). A repeated CTP was performed in 8 patients with a TCD-measured BFV increase > 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI. CONCLUSIONS Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD-measured BFV increase or persisting coma, do not contribute to information gain.

Value of Computed Tomographic Perfusion-Based Patient Selection for Intra-Arterial Acute Ischemic Stroke Treatment.

PubMed

Borst, Jordi; Berkhemer, Olvert A; Roos, Yvo B W E M; van Bavel, Ed; van Zwam, Wim H; van Oostenbrugge, Robert J; van Walderveen, Marianne A A; Lingsma, Hester F; van der Lugt, Aad; Dippel, Diederik W J; Yoo, Albert J; Marquering, Henk A; Majoie, Charles B L M

2015-12-01

The utility of computed tomographic perfusion (CTP)-based patient selection for intra-arterial treatment of acute ischemic stroke has not been proven in randomized trials and requires further study in a cohort that was not selected based on CTP. Our objective was to study the relationship between CTP-derived parameters and outcome and treatment effect in patients with acute ischemic stroke because of a proximal intracranial arterial occlusion. We included 175 patients who underwent CTP in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN). Association of CTP-derived parameters (ischemic-core volume, penumbra volume, and percentage ischemic core) with outcome was estimated with multivariable ordinal logistic regression as an adjusted odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale. Interaction between CTP-derived parameters and treatment effect was determined using multivariable ordinal logistic regression. Interaction with treatment effect was also tested for mismatch (core <70 mL; penumbra core >1.2; penumbra core >10 mL). The adjusted odds ratio for improved functional outcome for ischemic core, percentage ischemic core, and penumbra were 0.79 per 10 mL (95% confidence interval: 0.71-0.89; P<0.001), 0.82 per 10% (95% confidence interval: 0.66-0.90; P=0.002), and 0.97 per 10 mL (96% confidence interval: 0.92-1.01; P=0.15), respectively. No significant interaction between any of the CTP-derived parameters and treatment effect was observed. We observed no significant interaction between mismatch and treatment effect. CTP seems useful for predicting functional outcome, but cannot reliably identify patients who will not benefit from intra-arterial therapy. © 2015 American Heart Association, Inc.

Acute CT perfusion changes in seizure patients presenting to the emergency department with stroke-like symptoms: correlation with clinical and electroencephalography findings.

PubMed

Payabvash, S; Oswood, M C; Truwit, C L; McKinney, A M

2015-10-01

To determine acute computed tomography perfusion (CTP) changes in seizure patients presenting with stroke-like symptoms and to correlate those changes with clinical presentation and electroencephalography (EEG). The medical records of all patients who presented to the emergency department with acute stroke-like symptoms and underwent CTP (n=1085) over a 5.5-year period were reviewed. Patients were included who had primary seizure as the final diagnosis, and underwent CTP within 3 hours of symptom onset. A subset of patients had a follow-up EEG within 7 days. The perfusion changes and EEG findings were compared between different clinical presentations. Eighteen of 1085 patients (1.7%) who underwent CTP following an acute stroke-like presentation were included. The abnormality on CTP was usually focal, unilateral hyperperfusion - increased relative cerebral blood flow (rCBF) and volume (rCBV) (n=14/18), which most often affected the temporal lobe. Those patients who presented with a motor or speech deficit (n=12) had a higher temporal lobe rCBV, and rCBF, and lower relative mean transit time (rMTT) compared to those with non-focal neurological deficit at presentation. Early EEG was available in 13 patients; a sharp-spike epileptiform EEG discharge pattern (n=5) was associated with higher temporal lobe ipsilateral rCBF and rCBV, and lower rMTT on admission CTP examination. Seizure patients who present with a unilateral motor or speech deficit most commonly have contralateral hyperperfusion in the corresponding eloquent brain regions on the acute-stage CTP examination. In such patients, epileptiform discharges on the early follow-up EEG are associated with ipsilateral hyperperfusion on the admission CTP. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective, Combined Semi-Quantitative and Quantitative Assessment

PubMed Central

Padroni, Marina; Bernardoni, Andrea; Tamborino, Carmine; Roversi, Gloria; Borrelli, Massimo; Saletti, Andrea; De Vito, Alessandro; Azzini, Cristiano; Borgatti, Luca; Marcello, Onofrio; d’Esterre, Christopher; Ceruti, Stefano; Casetta, Ilaria; Lee, Ting-Yim; Fainardi, Enrico

2016-01-01

Introduction The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned. Methods 62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded. Results Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS≤2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome. Conclusions Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size. PMID:26824672

Comparison of CT perfusion summary maps to early diffusion-weighted images in suspected acute middle cerebral artery stroke.

PubMed

Benson, John; Payabvash, Seyedmehdi; Salazar, Pascal; Jagadeesan, Bharathi; Palmer, Christopher S; Truwit, Charles L; McKinney, Alexander M

2015-04-01

To assess the accuracy and reliability of one vendor's (Vital Images, Toshiba Medical, Minnetonka, MN) automated CT perfusion (CTP) summary maps in identification and volume estimation of infarcted tissue in patients with acute middle cerebral artery (MCA) distribution infarcts. From 1085 CTP examinations over 5.5 years, 43 diffusion-weighted imaging (DWI)-positive patients were included who underwent both CTP and DWI <12 h after symptom onset, with another 43 age-matched patients as controls (DWI-negative). Automated delay-corrected postprocessing software (DC-SVD) generated both infarct "core only" and "core+penumbra" CTP summary maps. Three reviewers independently tabulated Alberta Stroke Program Early CT scores (ASPECTS) of both CTP summary maps and coregistered DWI. Of 86 included patients, 36 had DWI infarct volumes ≤70 ml, 7 had volumes >70 ml, and 43 were negative; the automated CTP "core only" map correctly classified each as >70 ml or ≤70 ml, while the "core+penumbra" map misclassified 4 as >70 ml. There were strong correlations between DWI volume with both summary map-based volumes: "core only" (r=0.93), and "core+penumbra" (r=0.77) (both p<0.0001). Agreement between ASPECTS scores of infarct core on DWI with summary maps was 0.65-0.74 for "core only" map, and 0.61-0.65 for "core+penumbra" (both p<0.0001). Using DWI-based ASPECTS scores as the standard, the accuracy of the CTP-based maps were 79.1-86.0% for the "core only" map, and 83.7-88.4% for "core+penumbra." Automated CTP summary maps appear to be relatively accurate in both the detection of acute MCA distribution infarcts, and the discrimination of volumes using a 70 ml threshold. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dry Sintering Meets Wet Silver-Ion "Soldering": Charge-Transfer Plasmon Engineering of Solution-Assembled Gold Nanodimers From Visible to Near-Infrared I and II Regions.

PubMed

Fang, Lingling; Wang, Yueliang; Liu, Miao; Gong, Ming; Xu, An; Deng, Zhaoxiang

2016-11-07

Achieving highly tunable and localized surface plasmon resonance up to near infrared (NIR) regions is a key target in nanoplasmonics. In particular, a self-assembly process capable of producing highly uniform and solution-processable nanomaterials with tailor-made plasmonic properties is lacking. We herein address this problem through a conjunctive use of wet Ag + soldering and dry thermal sintering to produce nanodimer-derived structures with precisely engineered charge-transfer plasmon (CTP). The sintered dimers are water soluble, featuring gradually shifted CTP spanning an 800 nm wavelength range (up to NIR II). Upon silica removal, the products are grafted by DNA to offer surface functionality. This process is also adaptable to DNA-linked AuNP dimers toward plasmonic meta-materials via DNA-guided soldering and sintering. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

CT myocardial perfusion imaging: current status and future perspectives.

PubMed

Yang, Dong Hyun; Kim, Young-Hak

2017-07-01

Computed tomography myocardial perfusion (CTP) combined with coronary computed tomography angiography (CCTA) may constitute a "1-stop shop" for the noninvasive diagnosis of hemodynamically significant coronary stenosis during a single CT examination. CTP shows high diagnostic performance and provides incremental value over CCTA for the detection of hemodynamically significant coronary stenosis in patients with a high Agatston calcium score or coronary artery stents. Future studies should determine the optimal protocol and clinical value of CTP for guiding revascularization strategy and prognostication. In this article, we review the current status and future perspectives of CTP, focusing on technical considerations, clinical applications, and future research topics.

Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial.

PubMed

Manns, Michael; Samuel, Didier; Gane, Edward J; Mutimer, David; McCaughan, Geoff; Buti, Maria; Prieto, Martín; Calleja, José Luis; Peck-Radosavljevic, Markus; Müllhaupt, Beat; Agarwal, Kosh; Angus, Peter; Yoshida, Eric M; Colombo, Massimo; Rizzetto, Mario; Dvory-Sobol, Hadas; Denning, Jill; Arterburn, Sarah; Pang, Phillip S; Brainard, Diana; McHutchison, John G; Dufour, Jean-François; Van Vlierberghe, Hans; van Hoek, Bart; Forns, Xavier

2016-06-01

Treatment options are limited for patients infected by hepatitis C virus (HCV) with advanced liver disease. We assessed the safety and efficacy of ledipasvir, sofosbuvir, and ribavirin in patients with HCV genotype 1 or 4 and advanced liver disease. We did an open-label study at 34 sites in Europe, Canada, Australia, and New Zealand. Cohort A included patients with Child-Turcotte-Pugh class B (CTP-B) or CTP-C cirrhosis who had not undergone liver transplantation. Cohort B included post-transplantation patients who had either no cirrhosis; CTP-A, CTP-B, or CTP-C cirrhosis; or fibrosing cholestatic hepatitis. Patients in each group were randomly assigned (1:1) using a computer-generated randomisation sequence to receive 12 or 24 weeks of ledipasvir (90 mg) and sofosbuvir (400 mg) once daily (combination tablet), plus ribavirin (600-1200 mg daily). The primary endpoint was the proportion of patients achieving a sustained virological response 12 weeks after treatment (SVR12). All patients who received at least one dose of study drug were included in the safety analysis and all patients who received at least one dose of study drug and did not undergo liver transplantation during treatment were included in the efficacy analyses. Estimates of SVR12 and relapse rates and their two-sided 90% CI (Clopper-Pearson method) were provided. This exploratory phase 2 study was not powered for formal comparisons among treatment groups; no statistical hypothesis testing was planned or conducted. The trial is registered with EudraCT (number 2013-002802-30) and ClinicalTrials.gov (number NCT02010255). Between Jan 14, 2014, and Aug 19, 2014, 398 patients were screened. Of 333 patients who received treatment, 296 had genotype 1 HCV and 37 had genotype 4 HCV. In cohort A, among patients with genotype 1 HCV, SVR12 was achieved by 20 (87%, 90% CI 70-96) of 23 CTP-B patients with 12 weeks of treatment; 22 (96%, 81-100) of 23 CTP-B patients with 24 weeks of treatment; 17 (85%, 66-96) of 20 CTP-C patients (12 weeks treatment); and 18 (78%, 60-91) of 23 CTP-C patients (24 weeks treatment). In cohort B, among patients with genotype 1 HCV, SVR12 was achieved by 42 (93%, 84-98) of 45 patients without cirrhosis (12 weeks treatment); 44 (100%, 93-100) of 44 patients without cirrhosis (24 weeks treatment); 30 (100%, 91-100) of 30 CTP-A patients (12 weeks treatment); 27 (96%, 84-100) of 28 CTP-A patients (24 weeks treatment); 19 (95%, 78-100) of 20 CTP-B patients (12 weeks treatment); 20 (100%, 86-100) of 20 CTP-B patients (24 weeks treatment); one (50%, 3-98) of two CTP-C patients (12 weeks treatment); and four (80%, 34-99) of five CTP-C patients (24 weeks treatment). All five patients with fibrosing cholestatic hepatitis achieved SVR12 (100%, 90% CI 55-100). Among all patients with genotype 4 HCV, SVR12 was achieved by 14 (78%, 56-92) of 18 patients (12 weeks treatment) and 16 (94%, 75-100) of 17 patients (24 weeks treatment). Seven patients (2%) discontinued ledipasvir-sofosbuvir prematurely due to adverse events. 17 patients died, mainly from complications of hepatic decompensation. Ledipasvir-sofosbuvir and ribavirin provided high rates of SVR12 for patients with advanced liver disease, including those with decompensated cirrhosis before or after liver transplantation. Gilead Sciences. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization of cytidylyltransferase enzyme activity through high performance liquid chromatography.

PubMed

Brault, James P; Friesen, Jon A

2016-10-01

The cytidylyltransferases are a family of enzymes that utilize cytidine 5'-triphosphate (CTP) to synthesize molecules that are typically precursors to membrane phospholipids. The most extensively studied cytidylyltransferase is CTP:phosphocholine cytidylyltransferase (CCT), which catalyzes conversion of phosphocholine and CTP to cytidine diphosphocholine (CDP-choline), a step critical for synthesis of the membrane phospholipid phosphatidylcholine (PC). The current method used to determine catalytic activity of CCT measures production of radiolabeled CDP-choline from (14)C-labeled phosphocholine. The goal of this research was to develop a CCT enzyme assay that employed separation of non-radioactive CDP-choline from CTP. A C18 reverse phase column with a mobile phase of 0.1 M ammonium bicarbonate (98%) and acetonitrile (2%) (pH 7.4) resulted in separation of solutions of the substrate CTP from the product CDP-choline. A previously characterized truncated version of rat CCTα (denoted CCTα236) was used to test the HPLC enzyme assay by measuring CDP-choline product formation. The Vmax for CCTα236 was 3850 nmol/min/mg and K0.5 values for CTP and phosphocholine were 4.07 mM and 2.49 mM, respectively. The HPLC method was applied to glycerol 3-phosphate cytidylyltransferase (GCT) and CTP:2-C-methyl-D-erythritol-4-phosphate cytidylyltransferase synthetase (CMS), members of the cytidylyltransferase family that produce CDP-glycerol and CDP-methylerythritol, respectively. Copyright © 2016 Elsevier Inc. All rights reserved.

A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study

PubMed Central

Park, Won; Hrycaj, Pawel; Jeka, Slawomir; Kovalenko, Volodymyr; Lysenko, Grygorii; Miranda, Pedro; Mikazane, Helena; Gutierrez-Ureña, Sergio; Lim, MieJin; Lee, Yeon-Ah; Lee, Sang Joon; Kim, HoUng; Yoo, Dae Hyun; Braun, Jürgen

2013-01-01

Objectives To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS). Methods Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed. Results Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0  μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively. Conclusions The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30. PMID:23687259

Comparison of the pharmacokinetics and safety of three formulations of infliximab (CT-P13, EU-approved reference infliximab and the US-licensed reference infliximab) in healthy subjects: a randomized, double-blind, three-arm, parallel-group, single-dose, Phase I study.

PubMed

Park, Won; Lee, Sang Joon; Yun, Jihye; Yoo, Dae Hyun

2015-01-01

To compare the pharmacokinetics (PK), safety and tolerability of biosimilar infliximab (CT-P13 [Remsima(®), Inflectra(®)]) with two formulations of the reference medicinal product (RMP) (Remicade(®)) from either Europe (EU-RMP) or the USA (US-RMP). This was a double-blind, three-arm, parallel-group study (EudraCT number: 2013-003173-10). Healthy subjects received single doses (5 mg/kg) of CT-P13 (n = 71), EU-RMP (n = 71) or US-RMP (n = 71). The primary objective was to compare the PK profiles for the three formulations. Assessments of comparative safety and tolerability were secondary objectives. Baseline demographics were well balanced across the three groups. Primary end points (Cmax, AUClast and AUCinf) were equivalent between all formulations (CT-P13 vs EU-RMP; CT-P13 vs US-RMP; EU-RMP vs US-RMP). All other PK end points supported the high similarity of the three treatments. Tolerability profiles of the formulations were similar. The PK profile of CT-P13 is highly similar to EU-RMP and US-RMP. All three formulations were equally well tolerated.

A Phenotypic Based Target Screening Approach Delivers New Antitubercular CTP Synthetase Inhibitors.

PubMed

Esposito, Marta; Szadocka, Sára; Degiacomi, Giulia; Orena, Beatrice S; Mori, Giorgia; Piano, Valentina; Boldrin, Francesca; Zemanová, Júlia; Huszár, Stanislav; Barros, David; Ekins, Sean; Lelièvre, Joel; Manganelli, Riccardo; Mattevi, Andrea; Pasca, Maria Rosalia; Riccardi, Giovanna; Ballell, Lluis; Mikušová, Katarína; Chiarelli, Laurent R

2017-06-09

Despite its great potential, the target-based approach has been mostly unsuccessful in tuberculosis drug discovery, while whole cell phenotypic screening has delivered several active compounds. However, for many of these hits, the cellular target has not yet been identified, thus preventing further target-based optimization of the compounds. In this context, the newly validated drug target CTP synthetase PyrG was exploited to assess a target-based approach of already known, but untargeted, antimycobacterial compounds. To this purpose the publically available GlaxoSmithKline antimycobacterial compound set was assayed, uncovering a series of 4-(pyridin-2-yl)thiazole derivatives which efficiently inhibit the Mycobacterium tuberculosis PyrG enzyme activity, one of them showing low activity against the human CTP synthetase. The three best compounds were ATP binding site competitive inhibitors, with K i values ranging from 3 to 20 μM, but did not show any activity against a small panel of different prokaryotic and eukaryotic kinases, thus demonstrating specificity for the CTP synthetases. Metabolic labeling experiments demonstrated that the compounds directly interfere not only with CTP biosynthesis, but also with other CTP dependent biochemical pathways, such as lipid biosynthesis. Moreover, using a M. tuberculosis pyrG conditional knock-down strain, it was shown that the activity of two compounds is dependent on the intracellular concentration of the CTP synthetase. All these results strongly suggest a role of PyrG as a target of these compounds, thus strengthening the value of this kind of approach for the identification of new scaffolds for drug development.

Prevalence of and Factors Associated With Minimal Hepatic Encephalopathy in Patients With Cirrhosis of Liver.

PubMed

Bale, Abhijith; Pai, C Ganesh; Shetty, Shiran; Balaraju, Girisha; Shetty, Anurag

2018-06-01

Minimal hepatic encephalopathy (MHE), though highly prevalent, is a frequently underdiagnosed complication of cirrhosis of the liver. Because lack of time is reported as the major reason for non-testing, identifying patients at high risk of MHE would help in targeting them for screening. We aimed to determine the factors associated with MHE to help identify patient subgroups with a higher risk of MHE for targeted screening. Patients with cirrhosis of liver presenting between April 2015 and November 2016 were included. Those with a Psychometric Hepatic Encephalopathy Score (PHES) of ≤-5 points on psychometric testing were diagnosed to have MHE. Various demographic, clinical and laboratory parameters were included in a univariate and later multiple logistic regression models. Of the 180 (male = 166, 92.2%) patients included 94 (52.2%) had MHE. Though serum albumin, serum total bilirubin, serum aspartate aminotransferase, international normalized ration, Child-Turcotte-Pugh and Model-For-End-Stage-Liver-Disease scores were significant on univariate analysis, only CTP score was found to be significantly associated with MHE ( P  = 0.002) on multivariate analysis. A higher CTP class was associated with a higher risk of the presence of MHE. The Odds ratio for having MHE was higher with CTP classes of B ( P  ≤ 0.001) and C ( P  ≤ 0.001) compared to class A. MHE is a common complication in patients with cirrhosis of liver and higher CTP scores independently predict the presence of MHE. Patients with CTP class B and C have a higher risk of suffering from MHE than CTP class A. Screening of patients in CTP class B and C is likely to increase the MHE detection rates while saving time, although select CTP class A patients may also need screening in view of public safety or poor quality of life.

Efficacy of Stent-Retriever Thrombectomy in Magnetic Resonance Imaging Versus Computed Tomographic Perfusion-Selected Patients in SWIFT PRIME Trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke).

PubMed

Menjot de Champfleur, Nicolas; Saver, Jeffrey L; Goyal, Mayank; Jahan, Reza; Diener, Hans-Christoph; Bonafe, Alain; Levy, Elad I; Pereira, Vitor M; Cognard, Christophe; Yavagal, Dileep R; Albers, Gregory W

2017-06-01

The majority of patients enrolled in SWIFT PRIME trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke) had computed tomographic perfusion (CTP) imaging before randomization; 34 patients were randomized after magnetic resonance imaging (MRI). Patients with middle cerebral artery and distal carotid occlusions were randomized to treatment with tPA (tissue-type plasminogen activator) alone or tPA+stentriever thrombectomy. The primary outcome was the distribution of the modified Rankin Scale score at 90 days. Patients with the target mismatch profile for enrollment were identified on MRI and CTP. MRI selection was performed in 34 patients; CTP in 139 patients. Baseline National Institutes of Health Stroke Scale score was 17 in both groups. Target mismatch profile was present in 95% (MRI) versus 83% (CTP). A higher percentage of the MRI group was transferred from an outside hospital ( P =0.02), and therefore, the time from stroke onset to randomization was longer in the MRI group ( P =0.003). Time from emergency room arrival to randomization did not differ in CTP versus MRI-selected patients. Baseline ischemic core volumes were similar in both groups. Reperfusion rates (>90%/TICI [Thrombolysis in Cerebral Infarction] score 3) did not differ in the stentriever-treated patients in the MRI versus CTP groups. The primary efficacy analysis (90-day mRS score) demonstrated a statistically significant benefit in both subgroups (MRI, P =0.02; CTP, P =0.01). Infarct growth was reduced in the stentriever-treated group in both MRI and CTP groups. Time to randomization was significantly longer in MRI-selected patients; however, site arrival to randomization times were not prolonged, and the benefits of endovascular therapy were similar. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461. © 2017 American Heart Association, Inc.

Treatment of hepatitis C virus infection in patients with cirrhosis and predictive value of model for end-stage liver disease: Analysis of data from the Hepa-C registry.

PubMed

Fernández Carrillo, Carlos; Lens, Sabela; Llop, Elba; Pascasio, Juan Manuel; Crespo, Javier; Arenas, Juan; Fernández, Inmaculada; Baliellas, Carme; Carrión, José Antonio; de la Mata, Manuel; Buti, Maria; Castells, Lluís; Albillos, Agustín; Romero, Manuel; Turnes, Juan; Pons, Clara; Moreno-Planas, José María; Moreno-Palomares, José Javier; Fernández-Rodriguez, Conrado; García-Samaniego, Javier; Prieto, Martín; Fernández Bermejo, Miguel; Salmerón, Javier; Badia, Ester; Salcedo, Magdalena; Herrero, José Ignacio; Granados, Rafael; Blé, Michel; Mariño, Zoe; Calleja, José Luis

2017-06-01

Direct-acting antiviral agents (DAAs) are highly effective and well tolerated in patients with chronic hepatitis C virus infection, including those with compensated cirrhosis. However, fewer data are available in patients with more advanced liver disease. Our retrospective, noninterventional, national, multicenter study in patients from the Spanish Hepa-C registry investigated the effectiveness and safety of interferon-free DAA regimens in patients with advanced liver disease, including those with decompensated cirrhosis, in routine practice (all currently approved regimens were registered). Patients transplanted during treatment or within 12 weeks of completing treatment were excluded. Among 843 patients with cirrhosis (Child-Turcotte-Pugh [CTP] class A, n = 564; CTP class B/C, n = 175), 90% achieved sustained virologic response 12 weeks after treatment (SVR12). Significant differences in SVR12 and relapse rates were observed between CTP class A and CTP class B/C patients (94% versus 78%, and 4% versus 14%, respectively; both P < 0.001). Serious adverse events (SAEs) were more common in CTP class B/C versus CTP class A patients (50% versus 12%, respectively; P < 0.001). Incident decompensation was the most common serious adverse event (7% overall). Death rate during the study period was 16/843 (2%), significantly higher among CTP class B/C versus CTP class A patients (6.4% versus 0.9%; P < 0.001). Baseline Model for End-Stage Liver Disease (MELD) score alone (cut-off 18) was the best predictor of survival. Patients with decompensated cirrhosis receiving DAAs present lower response rates and experience more SAEs. In this setting, a MELD score ≥18 may help clinicians to identify those patients with a higher risk of complications and to individualize treatment decisions. (Hepatology 2017;65:1810-1822). © 2017 by the American Association for the Study of Liver Diseases.

Correction for Delay and Dispersion Results in More Accurate Cerebral Blood Flow Ischemic Core Measurement in Acute Stroke.

PubMed

Lin, Longting; Bivard, Andrew; Kleinig, Timothy; Spratt, Neil J; Levi, Christopher R; Yang, Qing; Parsons, Mark W

2018-04-01

This study aimed to assess how the ischemic core measured by perfusion computed tomography (CTP) was affected by the delay and dispersion effect. Ischemic stroke patients having CTP performed within 6 hours of onset were included. The CTP data were processed twice, generating standard cerebral blood flow (sCBF) and delay- and dispersion-corrected CBF (ddCBF), respectively. Ischemic core measured by the sCBF and ddCBF was then compared at the relative threshold <30% of normal tissue. Two references for ischemic core were used: acute diffusion-weighted imaging or 24-hour diffusion-weighted imaging in patients with complete recanalization. Difference of core volume between CTP and diffusion-weighted imaging was estimated by Mann-Whitney U test and limits of agreement. Patients were also classified into favorable and unfavorable CTP patterns. The imaging pattern classification by sCBF and ddCBF was compared by the χ 2 test; their respective ability to predict good clinical outcome (3-month modified Rankin Scale score) was tested in logistic regression. Fifty-five patients were included in this study. Median sCBF ischemic core volume was 38.5 mL (12.4-61.9 mL), much larger than the median core volume of 17.2 mL measured by ddCBF (interquartile range, 5.5-38.8; P <0.001). Moreover, compared with sCBF <30%, ddCBF <30% measured the ischemic core much closer to diffusion-weighted imaging core references, with the mean volume difference of -0.1 mL (95% limits of agreement, -25.4 to 25.2; P =0.97) and 16.7 mL (95% limits of agreement, -21.7 to 55.2; P <0.001), respectively. Imaging patterns defined by sCBF showed a difference to that defined by ddCBF ( P <0.001), with 12 patients classified as favorable imaging patterns by ddCBF but as unfavorable by sCBF. The favorable imaging pattern classified by ddCBF, compared with sCBF classification, had higher predictive power for good clinical outcome (odds ratio, 7.8 [2-30.5] and 3.1 [0.9-11], respectively). Delay and dispersion correction increases the accuracy of ischemic core measurement on CTP. © 2018 American Heart Association, Inc.

Reversible hemispheric hypoperfusion in two cases of SMART syndrome.

PubMed

Wai, Karmen; Balabanski, Anna; Chia, Nicholas; Kleinig, Timothy

2017-09-01

Stroke-like migraine attacks after radiation therapy (SMART) syndrome manifests as prolonged episodes of cortical dysfunction, years after cranial irradiation. We present two cases demonstrating reversible hemispheric hypoperfusion. Case 1 presented with left hemispheric symptoms following previous similar episodes. CT perfusion (CTP) demonstrated reversible hemispheric hypoperfusion; subsequent investigations were consistent with SMART syndrome. Case 2 presented following the third episode of a hemispheric syndrome with near-identical CTP abnormalities. L-arginine was administered with rapid reversal of clinical and CTP abnormalities. We conclude that SMART syndrome may demonstrate significant hypoperfusion on hyperacute CTP without subsequent infarction. Impaired cerebrovascular autoregulation probably contributes to cortical dysfunction in SMART syndrome. L-arginine warrants investigation as a potential treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety and feasibility of leadless pacemaker in patients undergoing atrioventricular node ablation for atrial fibrillation.

PubMed

Yarlagadda, Bharath; Turagam, Mohit K; Dar, Tawseef; Jangam, Pragna; Veerapaneni, Vaishnavi; Atkins, Donita; Bommana, Sudharani; Friedman, Paul; Deshmukh, Abhishek J; Doshi, Rahul; Reddy, Vivek Y; Dukkipati, Srinivas R; Natale, Andrea; Lakkireddy, Dhanunjaya

2018-03-01

Atrioventricular node (AVN) ablation and permanent pacing is an established strategy for rate control in the management of symptomatic atrial fibrillation (AF). Leadless pacemakers (LPs) can overcome some of the short-term and long-term limitations of conventional transvenous pacemakers (CTPs). The purpose of this study was to compare the feasibility and safety of LP with those of single-chamber CTP in patients with AF undergoing AVN ablation. We conducted a multicenter observational study of patients undergoing AVN ablation and pacemaker implantation (LP vs single-chamber CTP) between February 2014 and November 2016. The primary efficacy end points were acceptable sensing (R wave ≥5.0 mV) and pacing thresholds (≤2.0 V at 0.4 ms) at follow-up. Safety end points included device-related major and minor (early ≤1 month, late >1 month) adverse events. A total of 127 patients with LP (n = 60) and CTP (n = 67) were studied. The median follow-up was 12 months (interquartile range 12-18 months). Ninety-five percent of the LP group and 97% of the CTP group met the primary efficacy end point at follow-up (57 of 60 vs 65 of 67; P = .66). There was 1 major adverse event (loss of pacing and sensing) in the LP group and 2 (lead dislodgement) in the CTP group (1 of 60 vs 2 of 67; P = 1.00). There were 6 minor adverse events (5 early and 1 late) in the LP group and 3 (early) in the CTP group (6 of 60 vs 3 of 67; P = .30). Our results demonstrate the feasibility and safety of LP compared with CTP in patients undergoing AVN ablation for AF. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

A proposed procedure for derivation of regulatory values for carcinogenic airborne polycyclic aromatic hydrocarbons (PAHs) based on coal tar pitch (CTP) volatiles.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foureman, G.L.; Smith, R.L.

A procedure for estimating upper bound lifetime human cancer risk from air levels of six common carcinogenic polycyclic aromatic hydrocarbons (PAHs), termed APAHs of concern, is proposed. These PAHs are benzo(a)pyrene, benz(a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene, indeno(1,2,3-c,d)pyrene, and chrysene. In application, this proposed procedure would regard any given air level obtained for a APAH of concern to originate from a standard mixture of coal tar pitch (CTP). The given air level for the APAHs of concern is then related to a corresponding air level of CTP and thence, to an inhalation unit cancer risk calculated for CTP. Reference values for the proceduremore » are the relative and absolute PAH composition of a CTP standard (SRM-1597) and the inhalation unit cancer risk. Qualitative characterization of the results are a vital part of the procedure especially when more than one APAH of concern{at} is being considered. Toxic equivalency factors (TEFs) may be used as an evaluative tool in characterization of the procedure and outcome. Limitations of this proposed procedure include the uneven database for the reference values and the inability to consider air samples inclusive of another common carcinogenic PAH, dibenz(a,h)anthracene, due to its lack of documentation in CTP and high TEF« less

Clinical experience with infliximab biosimilar Remsima (CT-P13) in inflammatory bowel disease patients

PubMed Central

Jahnsen, Jørgen

2016-01-01

Many reference biological therapies have now reached or are near to patent expiry, and therefore a number of biosimilars have been or will be developed. The term biosimilar can be defined as a biotherapeutic product that is similar in efficacy, safety and quality to the licensed reference product. Biosimilars may lead to a reduced price and significant cost savings for the health community and hopefully more patients globally will have easier access to biological therapy when indicated. CT-P13, which is a TNF-alfa inhibitor, is the first monoclonal antibody biosimilar being used in clinical practice. The drug is approved for all indications as an innovator product although clinical efficacy has only been demonstrated in rheumatic diseases. Until now the number of patients with inflammatory bowel disease (IBD) treated with CT-P13 is confined, but experience is continuously growing. Based on current data, CT-P13 seems to be efficacious and generally well tolerated in IBD especially in patients who are naïve to biological therapy. Knowledge with regard to interchangeability between CT-P13 and the originator infliximab is however, still rather sparse and more data are desired. Immunogenicity and long-term safety related to CT-P13 are other areas of great importance and good and reliable postmarketing pharmacovigilance is therefore required in the coming years. PMID:27134662

Clinical development of CT-P10 and other biosimilar cancer therapeutics.

PubMed

Kim, Won Seog; Coiffier, Bertrand; Kwon, Hyuk-Chan; Kim, SuYeon

2017-05-01

Biosimilars are highly similar versions of approved biologic drugs that may confer equivalent efficacy at a reduced cost. Patents for several biological cancer therapeutics are past or approaching expiry, presenting an opportunity to increase affordability and global accessibility of key drugs through the development of biosimilars. To receive approval, a biosimilar must show no clinically meaningful differences from the reference product in terms of efficacy or safety. The first monoclonal antibody biosimilar cancer therapeutic to gain approval was CT-P10, a biosimilar of rituximab. Here, we review the oncology clinical development program for CT-P10, providing insights into the rationale for, and design of, CT-P10 clinical trials in patients with cancer. Trials of biosimilar cancer therapeutics in development are also discussed.

A Disruption of ctpA Encoding Carboxy-Terminal Protease Attenuates Burkholderia mallei and Induces Partial Protection in CD1 Mice

DTIC Science & Technology

2008-06-03

etiologic agent of glanders in solipeds (horses, mules and donkeys), and incidentally in carnivores and humans. Little is known about the molecular...disintegrated cell envelopes. Furthermore, relative to the wild type, the ctpA mutant displayed slower growth in vitro and less ability to survive in...IgG2a and were partially protected against chal- lenge with wild type B. mallei ATCC 23344. These findings suggest that CtpA regulates in vitro growth

Following DNA chain extension and protein conformational changes in crystals of a Y-family DNA polymerase via Raman crystallography.

PubMed

Espinoza-Herrera, Shirly J; Gaur, Vineet; Suo, Zucai; Carey, Paul R

2013-07-23

Y-Family DNA polymerases are known to bypass DNA lesions in vitro and in vivo. Sulfolobus solfataricus DNA polymerase (Dpo4) was chosen as a model Y-family enzyme for investigating the mechanism of DNA synthesis in single crystals. Crystals of Dpo4 in complexes with DNA (the binary complex) in the presence or absence of an incoming nucleotide were analyzed by Raman microscopy. (13)C- and (15)N-labeled d*CTP, or unlabeled dCTP, were soaked into the binary crystals with G as the templating base. In the presence of the catalytic metal ions, Mg(2+) and Mn(2+), nucleotide incorporation was detected by the disappearance of the triphosphate band of dCTP and the retention of *C modes in the crystal following soaking out of noncovalently bound C(or *C)TP. The addition of the second coded base, thymine, was observed by adding cognate dTTP to the crystal following a single d*CTP addition. Adding these two bases caused visible damage to the crystal that was possibly caused by protein and/or DNA conformational change within the crystal. When d*CTP is soaked into the Dpo4 crystal in the absence of Mn(2+) or Mg(2+), the primer extension reaction did not occur; instead, a ternary protein·template·d*CTP complex was formed. In the Raman difference spectra of both binary and ternary complexes, in addition to the modes of d(*C)CTP, features caused by ring modes from the template/primer bases being perturbed and from the DNA backbone appear, as well as features from perturbed peptide and amino acid side chain modes. These effects are more pronounced in the ternary complex than in the binary complex. Using standardized Raman intensities followed as a function of time, the C(*C)TP population in the crystal was maximal at ∼20 min. These remained unchanged in the ternary complex but declined in the binary complexes as chain incorporation occurred.

A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study

PubMed Central

Yoo, Dae Hyun; Hrycaj, Pawel; Miranda, Pedro; Ramiterre, Edgar; Piotrowski, Mariusz; Shevchuk, Sergii; Kovalenko, Volodymyr; Prodanovic, Nenad; Abello-Banfi, Mauricio; Gutierrez-Ureña, Sergio; Morales-Olazabal, Luis; Tee, Michael; Jimenez, Renato; Zamani, Omid; Lee, Sang Joon; Kim, HoUng; Park, Won; Müller-Ladner, Ulf

2013-01-01

Objectives To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. Methods Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5–25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. Results At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI −6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28–CRP, ACR–EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. Conclusions CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. ClinicalTrials.gov Identifier NCT01217086 PMID:23687260

California Transportation Plan 2025.

DOT National Transportation Integrated Search

2006-04-01

The California Transportation Plan 2025 (CTP) offers a blueprint for meeting : the States future mobility needs. The CTP is a long-range transportation : policy plan that explores the social, economic, and technological trends : and demographic ch...

A new sampling scheme for developing metamodels with the zeros of Chebyshev polynomials

NASA Astrophysics Data System (ADS)

Wu, Jinglai; Luo, Zhen; Zhang, Nong; Zhang, Yunqing

2015-09-01

The accuracy of metamodelling is determined by both the sampling and approximation. This article proposes a new sampling method based on the zeros of Chebyshev polynomials to capture the sampling information effectively. First, the zeros of one-dimensional Chebyshev polynomials are applied to construct Chebyshev tensor product (CTP) sampling, and the CTP is then used to construct high-order multi-dimensional metamodels using the 'hypercube' polynomials. Secondly, the CTP sampling is further enhanced to develop Chebyshev collocation method (CCM) sampling, to construct the 'simplex' polynomials. The samples of CCM are randomly and directly chosen from the CTP samples. Two widely studied sampling methods, namely the Smolyak sparse grid and Hammersley, are used to demonstrate the effectiveness of the proposed sampling method. Several numerical examples are utilized to validate the approximation accuracy of the proposed metamodel under different dimensions.

Mitochondrial and Plasma Membrane Citrate Transporters: Discovery of Selective Inhibitors and Application to Structure/Function Analysis

PubMed Central

Sun, Jiakang; Aluvila, Sreevidya; Kotaria, Rusudan; Mayor, June A.; Walters, D. Eric; Kaplan, Ronald S.

2010-01-01

Cytoplasmic citrate is the prime carbon source for fatty acid, triacylglycerol, and cholesterol biosyntheses, and also regulates glucose metabolism via its allosteric inhibition of phosphofructokinase. It originates either via the efflux of citrate from the mitochondrial matrix on the inner membrane citrate transport protein (CTP) or via the influx of extracellular citrate on the plasma membrane citrate transporter (PMCT). Despite their common substrate, the two transport proteins share little sequence similarity and they transport citrate via fundamentally different mechanisms. We tested the ability of a set of previously identified CTP inhibitors, to inhibit the PMCT. We found that of the top 10 CTP inhibitors only one substantially inhibited the PMCT. Conversely, we identified two other inhibitors that inhibited the PMCT but had little effect on the CTP. All three identified PMCT inhibitors displayed a noncompetitive mechanism. Furthermore, models to explain inhibitor interactions with the CTP are proposed. As part of the present studies a PMCT homology model has been developed based on the crystal structure of the leucine transporter, and a possible citrate binding site has been identified and its composition compared with the two known citrate binding sites present within the CTP. The ability to selectively inhibit the PMCT may prove key to the pharmacologic amelioration of metabolic disorders resulting from the synthesis of excess lipid, cholesterol, and glucose, including human obesity, hyperlipidemia, hyper-cholesterolemia, and Type 2 diabetes. PMID:20686672

Low dose CT perfusion in acute ischemic stroke.

PubMed

Murphy, Amanda; So, Aaron; Lee, Ting-Yim; Symons, Sean; Jakubovic, Raphael; Zhang, Liying; Aviv, Richard I

2014-12-01

The purpose of this investigation is to determine if CT perfusion (CTP) measurements at low doses (LD = 20 or 50 mAs) are similar to those obtained at regular doses (RD = 100 mAs), with and without the addition of adaptive statistical iterative reconstruction (ASIR). A single-center, prospective study was performed in patients with acute ischemic stroke (n = 37; 54% male; age = 74 ± 15 years). Two CTP scans were performed on each subject: one at 100 mAs (RD) and one at either 50 or 20 mAs (LD). CTP parameters were compared between the RD and LD scans in regions of ischemia, infarction, and normal tissue. Differences were determined using a within-subjects ANOVA (p < 0.05) followed by a paired t test post hoc analysis (p < 0.01). At 50 mAs, there was no significant difference between cerebral blood flow (CBF), cerebral blood volume (CBV), or time to maximum enhancement (Tmax) values for the RD and LD scans in the ischemic, infarcted, or normal contralateral regions (p < 0.05). At 20 mAs, there were significant differences between the RD and LD scans for all parameters in the ischemic and normal tissue regions (p > 0.05). CTP-derived CBF and CBV are not different at 50 mAs compared to 100 mAs, even without the addition of ASIR. Current CTP protocols can be modified to reduce the effective dose by 50 % without altering CTP measurements.

Comparable long-term efficacy, as assessed by patient-reported outcomes, safety and pharmacokinetics, of CT-P13 and reference infliximab in patients with ankylosing spondylitis: 54-week results from the randomized, parallel-group PLANETAS study.

PubMed

Park, Won; Yoo, Dae Hyun; Jaworski, Janusz; Brzezicki, Jan; Gnylorybov, Andriy; Kadinov, Vladimir; Sariego, Irmgadt Goecke; Abud-Mendoza, Carlos; Escalante, William Jose Otero; Kang, Seong Wook; Andersone, Daina; Blanco, Francisco; Hong, Seung Suh; Lee, Sun Hee; Braun, Jürgen

2016-01-20

CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®) and is approved in Europe and elsewhere, mostly for the same indications as RP. The aim of this study was to compare the 54-week efficacy, immunogenicity, pharmacokinetics (PK) and safety of CT-P13 with RP in patients with ankylosing spondylitis (AS), with a focus on patient-reported outcomes (PROs). This was a multinational, double-blind, parallel-group study in patients with active AS. Participants were randomized (1:1) to receive CT-P13 (5 mg/kg) or RP (5 mg/kg) at weeks 0, 2, 6 and then every 8 weeks up to week 54. To assess responses, standardized assessment tools were used with an intention-to-treat analysis of observed data. Anti-drug antibodies (ADAs), PK parameters, and safety outcomes were also assessed. Of 250 randomized patients (n = 125 per group), 210 (84.0 %) completed 54 weeks of treatment, with similar completion rates between groups. At week 54, Assessment of Spondylo Arthritis international Society (ASAS)20 response, ASAS40 response and ASAS partial remission were comparable between treatment groups. Changes from baseline in PROs such as mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; CT-P13 -3.1 versus RP -2.8), Bath Ankylosing Spondylitis Functional Index (BASFI; -2.9 versus -2.7), and Short Form Health Survey (SF-36) scores (9.26 versus 10.13 for physical component summary; 7.30 versus 6.54 for mental component summary) were similar between treatment groups. At 54 weeks, 19.5 % and 23.0 % of patients receiving CT-P13 and RP, respectively, had ADAs. All observed PK parameters of CT-P13 and RP, including maximum and minimum serum concentrations, were similar through 54 weeks. The influence of ADAs on PK was similar in the two treatment groups. Most adverse events were mild or moderate in severity. There was no notable difference between treatment groups in the incidence of adverse events, serious adverse events, infections and infusion-related reactions. CT-P13 and RP have highly comparable efficacy (including PROs) and PK up to week 54. Over a 1-year period, CT-P13 was well tolerated and displayed a safety profile comparable to RP; no differences in immunogenicity were observed. ClinicalTrials.gov identifier: NCT01220518 . Registered 4 October 2010.

The P-type ATPase CtpG preferentially transports Cd2+ across the Mycobacterium tuberculosis plasma membrane.

PubMed

López, Marcela; Quitian, Laudy-Viviana; Calderón, Martha-Nancy; Soto, Carlos-Y

2018-04-01

P 1B -type ATPases are involved in heavy metal transport across the plasma membrane. Some Mycobacterium tuberculosis P-type ATPases are induced during infection, suggesting that this type of transporter could play a critical role in mycobacterial survival. To date, the ion specificity of M. tuberculosis heavy metal-transporting P 1B -ATPases is not well understood. In this work, we observed that, although divalent heavy metal cations such as Cu 2+ , Co 2+ , Ni 2+ , Zn 2+ Cd 2+ and Pb 2+ stimulate the ATPase activity of the putative P 1B -type ATPase CtpG in the plasma membrane, whole cells of M. smegmatis expressing CtpG only tolerate high levels of Cd 2+ and Cu 2+ . As indicator of the catalytic constant, Michaelis-Menten kinetics showed that CtpG embedded in the mycobacterial cell membrane has a V max /K m ratio 7.4-fold higher for Cd 2+ than for Cu 2+ ions. Thus, although CtpG can accept different substrates in vitro, this P-type ATPase transports Cd 2+ more efficiently than other heavy metal cations across the mycobacterial plasma membrane.

Potency assay development for cellular therapy products: an ISCT review of the requirements and experiences in the industry.

PubMed

Bravery, Christopher A; Carmen, Jessica; Fong, Timothy; Oprea, Wanda; Hoogendoorn, Karin H; Woda, Juliana; Burger, Scott R; Rowley, Jon A; Bonyhadi, Mark L; Van't Hof, Wouter

2013-01-01

The evaluation of potency plays a key role in defining the quality of cellular therapy products (CTPs). Potency can be defined as a quantitative measure of relevant biologic function based on the attributes that are linked to relevant biologic properties. To achieve an adequate assessment of CTP potency, appropriate in vitro or in vivo laboratory assays and properly controlled clinical data need to be created. The primary objective of a potency assay is to provide a mechanism by which the manufacturing process and the final product for batch release are scrutinized for quality, consistency and stability. A potency assay also provides the basis for comparability assessment after process changes, such as scale-up, site transfer and new starting materials (e.g., a new donor). Potency assays should be in place for early clinical development, and validated assays are required for pivotal clinical trials. Potency is based on the individual characteristics of each individual CTP, and the adequacy of potency assays will be evaluated on a case-by-case basis by regulatory agencies. We provide an overview of the expectations and challenges in development of potency assays specific for CTPs; several real-life experiences from the cellular therapy industry are presented as illustrations. The key observation and message is that aggressive early investment in a solid potency evaluation strategy can greatly enhance eventual CTP deployment because it can mitigate the risk of costly product failure in late-stage development. Copyright © 2013. Published by Elsevier Inc.

Error-prone bypass of O6-methylguanine by DNA polymerase of Pseudomonas aeruginosa phage PaP1.

PubMed

Gu, Shiling; Xiong, Jingyuan; Shi, Ying; You, Jia; Zou, Zhenyu; Liu, Xiaoying; Zhang, Huidong

2017-09-01

O 6 -Methylguanine (O 6 -MeG) is highly mutagenic and is commonly found in DNA exposed to methylating agents, generally leads to G:C to A:T mutagenesis. To study DNA replication encountering O 6 -MeG by the DNA polymerase (gp90) of P. aeruginosa phage PaP1, we analyzed steady-state and pre-steady-state kinetics of nucleotide incorporation opposite O 6 -MeG by gp90 exo - . O 6 -MeG partially inhibited full-length extension by gp90 exo - . O 6 -MeG greatly reduces dNTP incorporation efficiency, resulting in 67-fold preferential error-prone incorporation of dTTP than dCTP. Gp90 exo - extends beyond T:O 6 -MeG 2-fold more efficiently than C:O 6 -MeG. Incorporation of dCTP opposite G and incorporation of dCTP or dTTP opposite O 6 -MeG show fast burst phases. The pre-steady-state incorporation efficiency (k pol /K d,dNTP ) is decreased in the order of dCTP:G>dTTP:O 6 -MeG>dCTP:O 6 -MeG. The presence of O 6 -MeG at template does not affect the binding affinity of polymerase to DNA but it weakened their binding in the presence of dCTP and Mg 2+ . Misincorporation of dTTP opposite O 6 -MeG further weakens the binding affinity of polymerase to DNA. The priority of dTTP incorporation opposite O 6 -MeG is originated from the fact that dTTP can induce a faster conformational change step and a faster chemical step than dCTP. This study reveals that gp90 bypasses O 6 -MeG in an error-prone manner and provides further understanding in DNA replication encountering mutagenic alkylation DNA damage for P. aeruginosa phage PaP1. Copyright © 2017 Elsevier B.V. All rights reserved.

Low dose dynamic myocardial CT perfusion using advanced iterative reconstruction

NASA Astrophysics Data System (ADS)

Eck, Brendan L.; Fahmi, Rachid; Fuqua, Christopher; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.

2015-03-01

Dynamic myocardial CT perfusion (CTP) can provide quantitative functional information for the assessment of coronary artery disease. However, x-ray dose in dynamic CTP is high, typically from 10mSv to >20mSv. We compared the dose reduction potential of advanced iterative reconstruction, Iterative Model Reconstruction (IMR, Philips Healthcare, Cleveland, Ohio) to hybrid iterative reconstruction (iDose4) and filtered back projection (FBP). Dynamic CTP scans were obtained using a porcine model with balloon-induced ischemia in the left anterior descending coronary artery to prescribed fractional flow reserve values. High dose dynamic CTP scans were acquired at 100kVp/100mAs with effective dose of 23mSv. Low dose scans at 75mAs, 50mAs, and 25mAs were simulated by adding x-ray quantum noise and detector electronic noise to the projection space data. Images were reconstructed with FBP, iDose4, and IMR at each dose level. Image quality in static CTP images was assessed by SNR and CNR. Blood flow was obtained using a dynamic CTP analysis pipeline and blood flow image quality was assessed using flow-SNR and flow-CNR. IMR showed highest static image quality according to SNR and CNR. Blood flow in FBP was increasingly over-estimated at reduced dose. Flow was more consistent for iDose4 from 100mAs to 50mAs, but was over-estimated at 25mAs. IMR was most consistent from 100mAs to 25mAs. Static images and flow maps for 100mAs FBP, 50mAs iDose4, and 25mAs IMR showed comparable, clear ischemia, CNR, and flow-CNR values. These results suggest that IMR can enable dynamic CTP at significantly reduced dose, at 5.8mSv or 25% of the comparable 23mSv FBP protocol.

Evaluation of the pharmacokinetic equivalence and 54-week efficacy and safety of CT-P13 and innovator infliximab in Japanese patients with rheumatoid arthritis

PubMed Central

Takeuchi, Tsutomu; Yamanaka, Hisashi; Tanaka, Yoshiya; Sakurai, Takeo; Saito, Kazuyoshi; Ohtsubo, Hideo; Lee, Sang Joon; Nambu, Yoshihiro

2015-01-01

Objectives. To demonstrate the pharmacokinetic equivalence of CT-P13 and its innovator infliximab (IFX) in Japanese patients with rheumatoid arthritis (RA), and to compare the efficacy and safety of these drugs, administered for 54 weeks. Methods. In a randomized, double-blind, parallel-group, multicenter study, 3 mg/kg of CT-P13 or IFX, in combination with methotrexate (MTX) (6–16 mg/week), was administered for 54 weeks to Japanese active RA patients with an inadequate response to MTX, to demonstrate the pharmacokinetic equivalence, based on the area under the curve (AUCτ) (weeks 6–14) and Cmax (week 6) of these drugs, and to compare their efficacy and safety. Results. The CT-P13-to-IFX ratios (90% confidence intervals) of the geometric mean AUCτ and Cmax values in patients negative for antibodies to infliximab at week 14 were 111.62% (100.24–124.29%) and 104.09% (92.12–117.61%), respectively, demonstrating the pharmacokinetic equivalence of these drugs. In the full analysis set, CT-P13 and IFX showed comparable therapeutic effectiveness, as measured by the American College of Rheumatology, Disease Activity Score in 28 joints, the European League Against Rheumatism, and other efficacy criteria, at weeks 14 and 30. The incidence of adverse events was similar for these drugs. Conclusion. CT-P13 and IFX, administered at a dose of 3 mg/kg in combination with MTX to active RA patients, were pharmacokinetically equivalent and comparable in efficacy and safety. PMID:25736355

Antibacterial, anti-inflammatory, and bone-regenerative dual-drug-loaded calcium phosphate nanocarriers-in vitro and in vivo studies.

PubMed

Madhumathi, K; Rubaiya, Y; Doble, Mukesh; Venkateswari, R; Sampath Kumar, T S

2018-05-01

A dual local drug delivery system (DDS) composed of calcium phosphate bioceramic nanocarriers aimed at treating the antibacterial, anti-inflammatory, and bone-regenerative aspects of periodontitis has been developed. Calcium-deficient hydroxyapatite (CDHA, Ca/P = 1.61) and tricalcium phosphate (β-TCP) were prepared by microwave-accelerated wet chemical synthesis method. The phase purity of the nanocarriers was confirmed by x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR), while the transmission electron microscopy (TEM) confirmed their nanosized morphology. CDHA was selected as carrier for the antibiotic (tetracycline) while TCP was chosen as the anti-inflammatory drug (ibuprofen) carrier. Combined drug release profile was studied in vitro from CDHA/TCP (CTP) system and compared with a HA/TCP (BCP) biphasic system. The tetracycline and ibuprofen release rate was 71 and 23% from CTP system as compared to 63 and 20% from BCP system. CTP system also showed a more controlled drug release profile compared to BCP system. Modeling of drug release kinetics from CTP system indicated that the release follows Higuchi model with a non-typical Fickian diffusion profile. In vitro biological studies showed the CTP system to be biocompatible with significant antibacterial and anti-inflammatory activity. In vivo implantation studies on rat cranial defects showed greater bone healing and new bone formation in the drug-loaded CTP system compared to control (no carrier) at the end of 12 weeks. The in vitro and in vivo results suggest that the combined drug delivery platform can provide a comprehensive management for all bone infections requiring multi-drug therapy.

The Novel Zinc Finger Protein dASCIZ Regulates Mitosis in Drosophila via an Essential Role in Dynein Light-Chain Expression

PubMed Central

Zaytseva, Olga; Tenis, Nora; Mitchell, Naomi; Kanno, Shin-ichiro; Yasui, Akira; Heierhorst, Jörg; Quinn, Leonie M

2014-01-01

The essential zinc finger protein ASCIZ (also known as ATMIN, ZNF822) plays critical roles during lung organogenesis and B cell development in mice, where it regulates the expression of dynein light chain (DYNLL1/LC8), but its functions in other species including invertebrates are largely unknown. Here we report the identification of the Drosophila ortholog of ASCIZ (dASCIZ) and show that loss of dASCIZ function leads to pronounced mitotic delays with centrosome and spindle positioning defects during development, reminiscent of impaired dynein motor functions. Interestingly, similar mitotic and developmental defects were observed upon knockdown of the DYNLL/LC8-type dynein light chain Cutup (Ctp), and dASCIZ loss-of-function phenotypes could be suppressed by ectopic Ctp expression. Consistent with a genetic function of dASCIZ upstream of Ctp, we show that loss of dASCIZ led to reduced endogenous Ctp mRNA and protein levels and dramatically reduced Ctp–LacZ reporter gene activity in vivo, indicating that dASCIZ regulates development and mitosis as a Ctp transcription factor. We speculate that the more severe mitotic defects in the absence of ASCIZ in flies compared to mice may be due to redundancy with a second, ASCIZ-independent, Dynll2 gene in mammals in contrast to a single Ctp gene in Drosophila. Altogether, our data demonstrate that ASCIZ is an evolutionary highly conserved transcriptional regulator of dynein light-chain levels and a novel regulator of mitosis in flies. PMID:24336747

Assessment of hemodynamics in a rat model of liver cirrhosis with precancerous lesions using multislice spiral CT perfusion imaging.

PubMed

Ma, Guolin; Bai, Rongjie; Jiang, Huijie; Hao, Xuejia; Ling, Zaisheng; Li, Kefeng

2013-01-01

To develop an optimal scanning protocol for multislice spiral CT perfusion (CTP) imaging to evaluate hemodynamic changes in liver cirrhosis with diethylnitrosamine- (DEN-) induced precancerous lesions. Male Wistar rats were randomly divided into the control group (n = 80) and the precancerous liver cirrhosis group (n = 40). The control group received saline injection and the liver cirrhosis group received 50 mg/kg DEN i.p. twice a week for 12 weeks. All animals underwent plain CT scanning, CTP, and contrast-enhanced CT scanning. Scanning parameters were optimized by adjusting the diatrizoate concentration, the flow rate, and the delivery time. The hemodynamics of both groups was further compared using optimized multislice spiral CTP imaging. High-quality CTP images were obtained with following parameters: 150 kV; 150 mAs; 5 mm thickness, 5 mm interval; pitch, 1; matrix, 512 × 512; and FOV, 9.6 cm. Compared to the control group, the liver cirrhosis group had a significantly increased value of the hepatic arterial fraction and the hepatic artery perfusion (P < 0.05) but significantly decreased hepatic portal perfusion and mean transit time (P < 0.05). Multislice spiral CTP imaging can be used to evaluate the hemodynamic changes in the rat model of liver cirrhosis with precancerous lesions.

SU-E-J-26: Analysis of Image Quality in CBCT QA Using a Treatment Planning System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, M

2014-06-01

Purpose: The objective of this study is to propose an alternative QA technique that analyzes imaging quality(IQ) in CBCT-QA processing. Methods: A catphan phantom was used to take CT imaging data set that were imported into a treatment planning system - Eclipse. The image quality was analyzed in terms of in-slice geometry resolution, Hounsfield numbers(HU) accuracy, mean-slice thickness, edge-to-center uniformity, low contrast resolution, and high contrast spatial resolution in Eclipse workstation. The CBCT-QA was also analyzed by OBI-workstation and a commercial software. Comparison was made to evaluation feasibility in a TPS environment. Results: The analysis of IQ was conducted inmore » Eclipse v10.0 TPS. In-slice geometric resolution was measured between 2-rods in section CTP404 and repeated for all 4 rods with the difference between expected and measured values less than +/−0.1 cm. For HU, the difference between expected and measured values in HU was found much less than +/−40. Mean slice thickness measured by a distance on the wire proportional to scanner increment multiplying by a factor of 0.42. After repeating measurements to 4 wires, the average difference between expected and measured values was less +/−0.124 mm in slice thickness. HU uniformity was measured in section CTP486 with the tolerance less than +/−40 HU. Low contrast resolution in section CTP515 and high contrast resolution in section CTP528 were found to be 7 disks in diameter of 4 mm and 6 lp/cm, respectively. Eclipse TPS results indicated a good agreement to those obtained in OBI workstation and ImagePro software for major parameters. Conclusion: An analysis of IQ was proposed as an alternative CBCT QA processing. Based upon measured data assessment, proposed method was accurate and consistent to IQ evaluation and TG142 guideline. The approach was to utilize TPS resource, which can be valuable to re-planning, verification, and delivery in adaptive therapy.« less

Post-marketing study of biosimilar infliximab (CT-P13) to evaluate its safety and efficacy in Korea.

PubMed

Park, Sang Hyoung; Kim, Young-Ho; Lee, Ji Hyun; Kwon, Hyeok Jin; Lee, Suck-Ho; Park, Dong Il; Kim, Hyung Kil; Cheon, Jae Hee; Im, Jong Pil; Kim, You Sun; Lee, Sung Young; Lee, Sang Joon

2015-01-01

To evaluate the safety and efficacy of CT-P13 (Remsima(®)) in patients with inflammatory bowel disease (IBD) in South Korea. This post-marketing study included patients with active moderate-to-severe Crohn's disease (CD), fistulizing CD (FCD), or moderate-to-severe ulcerative colitis (UC) treated with CT-P13 and followed for 30 weeks. Assessments included treatment-emergent adverse events (TEAEs) and disease-specific clinical response and remission. No unexpected TEAEs were observed in the 173 patients recruited to date. TEAEs occurred in 18.1, 16.7, and 26.9% of CD, FCD, and UC patients, respectively. Treatment-related TEAEs occurred in 10% of patients and were mostly mild-moderate in severity. There were five serious TEAEs (two infusion-related reactions, two infections, one abdominal pain) and no cases of malignancy, pneumonia, or death. Positive outcomes for response/remission were reported regardless of whether patients had received prior infliximab or not. CT-P13 was well tolerated and efficacious in patients with IBD.

The development and application of a new tool to assess the adequacy of the content and timing of antenatal care

PubMed Central

2011-01-01

Background Current measures of antenatal care use are limited to initiation of care and number of visits. This study aimed to describe the development and application of a tool to assess the adequacy of the content and timing of antenatal care. Methods The Content and Timing of care in Pregnancy (CTP) tool was developed based on clinical relevance for ongoing antenatal care and recommendations in national and international guidelines. The tool reflects minimal care recommended in every pregnancy, regardless of parity or risk status. CTP measures timing of initiation of care, content of care (number of blood pressure readings, blood tests and ultrasound scans) and whether the interventions were received at an appropriate time. Antenatal care trajectories for 333 pregnant women were then described using a standard tool (the APNCU index), that measures the quantity of care only, and the new CTP tool. Both tools categorise care into 4 categories, from 'Inadequate' (both tools) to 'Adequate plus' (APNCU) or 'Appropriate' (CTP). Participants recorded the timing and content of their antenatal care prospectively using diaries. Analysis included an examination of similarities and differences in categorisation of care episodes between the tools. Results According to the CTP tool, the care trajectory of 10,2% of the women was classified as inadequate, 8,4% as intermediate, 36% as sufficient and 45,3% as appropriate. The assessment of quality of care differed significantly between the two tools. Seventeen care trajectories classified as 'Adequate' or 'Adequate plus' by the APNCU were deemed 'Inadequate' by the CTP. This suggests that, despite a high number of visits, these women did not receive the minimal recommended content and timing of care. Conclusions The CTP tool provides a more detailed assessment of the adequacy of antenatal care than the current standard index. However, guidelines for the content of antenatal care vary, and the tool does not at the moment grade over-use of interventions as 'Inappropriate'. Further work needs to be done to refine the content items prior to larger scale testing of the impact of the new measure. PMID:21896201

CT-P13: design, development, and place in therapy

PubMed Central

Gabbani, Tommaso; Deiana, Simona; Annese, Vito

2017-01-01

The introduction of biological agents has revolutionized the management of many life-threatening and debilitating immune-mediated diseases. Because of the high cost of biological drugs and their patent expiration, the market has opened to biosimilar agents, copy versions of the originators, which can lead to reduced health care expenditure and increase treatment access worldwide. CT-P13 is the first biosimilar of infliximab (IFX) and has been approved for the same indications as its originator drug. It obtained regulatory approval by the European Medicines Agency in September 2013 and by the US Food and Drug Administration in April 2016. The Phase I and Phase III clinical trials conducted in ankylosing spondylitis and rheumatoid arthritis have demonstrated pharmacokinetic and efficacy equivalence with comparable safety and immunogenicity to IFX. For these reasons, the use of CT-P13 has been extrapolated also to inflammatory bowel disease. There have been some initial concerns regarding the use of CT-P13 in inflammatory bowel disease patients, because of the lack of randomized controlled trials. However, emerging real-world data have further confirmed the comparability between CT-P13 and its reference product in terms of efficacy, safety, and immunogenicity, in patients naïve to the anti-tumor necrosis factor alpha agents and after switching from IFX, and will be summarized in this review. PMID:28652703

Extraction, purification, characterization and antioxidant activities of polysaccharides from Cistanche tubulosa.

PubMed

Zhang, Wiejie; Huang, Jing; Wang, Wei; Li, Qian; Chen, Yao; Feng, Weiwei; Zheng, Daheng; Zhao, Ting; Mao, Guanghua; Yang, Liuqing; Wu, Xiangyang

2016-12-01

An efficient ultrasonic-cellulase-assisted extraction (UCE) of Cistanche tubulosa polysaccharide (CTP) was established. The response surface methodology based on Box-Behnken Design was employed to further optimize extraction conditions. After quaternary ammonium salt precipitation, the polysaccharide of C. tubulosa was characterized by different techniques. The results showed that a maximum polysaccharide yield of 22.31±0.45% was achieved at a pH of 5.2 for 31.5min at 54.1°C. Compared to hot water extraction, the yield of CTP in UCE and polysaccharide content increased to 44.96% and 70.13±2.19%, respectively. There was no marked difference among polysaccharides extracted using different methods from the infrared spectrum. Ultrasonic-cellulase-assisted extraction polysaccharide showed a fibrous structure from scanning electron microscopy and was composed of rhamnose, mannose, glucose, and galactose in a molar ratio of 2.18:1:28.29:1.43 by gas chromatography. The circular dichroism results indicated that polysaccharides had a maximum positive peak around 210nm with different peak values. The thermogravimetric analysis and differential scanning calorimetry were used to test the thermostability of CTP. Besides, CTP demonstrated appreciable antioxidant potential on antioxidant experiments in vitro. The results suggested that UCE is an effective method for CTP extraction and its polysaccharide showed appreciable antioxidant activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification of a cardiac specific protein transduction domain by in vivo biopanning using a M13 phage peptide display library in mice.

PubMed

Zahid, Maliha; Phillips, Brett E; Albers, Sean M; Giannoukakis, Nick; Watkins, Simon C; Robbins, Paul D

2010-08-17

A peptide able to transduce cardiac tissue specifically, delivering cargoes to the heart, would be of significant therapeutic potential for delivery of small molecules, proteins and nucleic acids. In order to identify peptide(s) able to transduce heart tissue, biopanning was performed in cell culture and in vivo with a M13 phage peptide display library. A cardiomyoblast cell line, H9C2, was incubated with a M13 phage 12 amino acid peptide display library. Internalized phage was recovered, amplified and then subjected to a total of three rounds of in vivo biopanning where infectious phage was isolated from cardiac tissue following intravenous injection. After the third round, 60% of sequenced plaques carried the peptide sequence APWHLSSQYSRT, termed cardiac targeting peptide (CTP). We demonstrate that CTP was able to transduce cardiomyocytes functionally in culture in a concentration and cell-type dependent manner. Mice injected with CTP showed significant transduction of heart tissue with minimal uptake by lung and kidney capillaries, and no uptake in liver, skeletal muscle, spleen or brain. The level of heart transduction by CTP also was greater than with a cationic transduction domain. Biopanning using a peptide phage display library identified a peptide able to transduce heart tissue in vivo efficiently and specifically. CTP could be used to deliver therapeutic peptides, proteins and nucleic acid specifically to the heart.

Cannabis for therapeutic purposes: patient characteristics, access, and reasons for use.

PubMed

Walsh, Zach; Callaway, Robert; Belle-Isle, Lynne; Capler, Rielle; Kay, Robert; Lucas, Philippe; Holtzman, Susan

2013-11-01

The authorized and unauthorized use of cannabis for therapeutic purposes (CTP) has increased dramatically in recent years, and physicians have called for further research to better clarify the parameters of effective and appropriate use. We report findings from a large cross-sectional study of the use of CTP in Canada and compare use across medical conditions and across authorized and unauthorized users. We examined cannabis use history, medical conditions and symptoms, patterns of current use of CTP, modes of access and perceived effectiveness among 628 self-selected Canadians consumers of CTP. Participants were recruited from medical cannabis dispensaries and from organizations that assist users of CTP. Patients reported using cannabis to treat multiple symptoms, with sleep, pain, and anxiety being the most common. Cannabis was perceived to provide effective symptoms relief across medical conditions. Patterns of use were also consistent across medical conditions. Notable differences were observed with regard to modes of access. Across medical conditions respondents reported using cannabis to effectively address diverse symptoms. Results indicate a substantial disconnect between the therapeutic use of cannabis and research on the risks and benefits of such use; particularly with regard to the anxiolytic and sedative use of cannabis. Authorized and unauthorized users exhibited few meaningful differences with regard to medical conditions and patterns of use, but faced substantial differences regarding access. Copyright © 2013 Elsevier B.V. All rights reserved.

77 FR 21540 - Notice of Submission for OMB Review; Federal Student Aid; Comprehensive Transition Programs (CTP...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

... DEPARTMENT OF EDUCATION Notice of Submission for OMB Review; Federal Student Aid; Comprehensive Transition Programs (CTP) for Students With Intellectual Disabilities Expenditure Report SUMMARY: The Higher Education Opportunity Act, Public Law 110-315, added provisions for the Higher Education Act, as amended in...

Synthesis and polymerase activity of a fluorescent cytidine TNA triphosphate analogue

PubMed Central

Mei, Hui; Shi, Changhua; Jimenez, Randi M.; Wang, Yajun; Kardouh, Miramar

2017-01-01

Abstract Threose nucleic acid (TNA) is an artificial genetic polymer capable of undergoing Darwinian evolution to produce aptamers with affinity to specific targets. This property, coupled with a backbone structure that is refractory to nuclease digestion, makes TNA an attractive biopolymer system for diagnostic and therapeutic applications. Expanding the chemical diversity of TNA beyond the natural bases would enable the development of functional TNA molecules with enhanced physiochemical properties. Here, we describe the synthesis and polymerase activity of a fluorescent cytidine TNA triphosphate analogue (1,3-diaza-2-oxo-phenothiazine, tCfTP) that maintains Watson-Crick base pairing with guanine. Polymerase-mediated primer-extension assays reveal that tCfTP is efficiently added to the growing end of a TNA primer. Detailed kinetic assays indicate that tCfTP and tCTP have comparable rates for the first nucleotide incorporation step (kobs1). However, addition of the second nucleotide (kobs2) is 700-fold faster for tCfTP than tCTP due the increased effects of base stacking. Last, we found that TNA replication using tCfTP in place of tCTP exhibits 98.4% overall fidelity for the combined process of TNA transcription and reverse transcription. Together, these results expand the chemical diversity of enzymatically generated TNA molecules to include a hydrophobic base analogue with strong fluorescent properties that is compatible with in vitro selection. PMID:28472363

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases*

PubMed Central

Zhao, Linlin; Pence, Matthew G.; Christov, Plamen P.; Wawrzak, Zdzislaw; Choi, Jeong-Yun; Rizzo, Carmelo J.; Egli, Martin; Guengerich, F. Peter

2012-01-01

N2,3-Ethenoguanine (N2,3-ϵG) is one of the exocyclic DNA adducts produced by endogenous processes (e.g. lipid peroxidation) and exposure to bioactivated vinyl monomers such as vinyl chloride, which is a known human carcinogen. Existing studies exploring the miscoding potential of this lesion are quite indirect because of the lability of the glycosidic bond. We utilized a 2′-fluoro isostere approach to stabilize this lesion and synthesized oligonucleotides containing 2′-fluoro-N2,3-ϵ-2′-deoxyarabinoguanosine to investigate the miscoding potential of N2,3-ϵG by Y-family human DNA polymerases (pols). In primer extension assays, pol η and pol κ replicated through N2,3-ϵG, whereas pol ι and REV1 yielded only 1-base incorporation. Steady-state kinetics revealed that dCTP incorporation is preferred opposite N2,3-ϵG with relative efficiencies in the order of pol κ > REV1 > pol η ≈ pol ι, and dTTP misincorporation is the major miscoding event by all four Y-family human DNA pols. Pol ι had the highest dTTP misincorporation frequency (0.71) followed by pol η (0.63). REV1 misincorporated dTTP and dGTP with much lower frequencies. Crystal structures of pol ι with N2,3-ϵG paired to dCTP and dTTP revealed Hoogsteen-like base pairing mechanisms. Two hydrogen bonds were observed in the N2,3-ϵG:dCTP base pair, whereas only one appears to be present in the case of the N2,3-ϵG:dTTP pair. Base pairing mechanisms derived from the crystal structures explain the slightly favored dCTP insertion for pol ι in steady-state kinetic analysis. Taken together, these results provide a basis for the mutagenic potential of N2,3-ϵG. PMID:22910910

Common Grounds for Modelling Mathematics in Educational Software

ERIC Educational Resources Information Center

Neuper, Walther

2010-01-01

Two kinds of software, CAS and DGS, are starting to work towards mutual integration. This paper envisages common grounds for such integration based on principles of computer theorem proving (CTP). Presently, the CTP community seems to lack awareness as to which of their products' features might serve mathematics education from high-school to…

Attention to Form or Meaning? Error Treatment in the Bangalore Project.

ERIC Educational Resources Information Center

Beretta, Alan

1989-01-01

Reports on an evaluation of the Bangalore/Madras Communicational Teaching Project (CTP), a content-based approach to language learning. Analysis of 21 lesson transcripts revealed a greater incidence of error treatment of content than linguistic error, consonant with the CTP focus on meaning rather than form. (26 references) (Author/CB)

Evaluation of the Bangalore/Madras Communicational Teaching Project.

ERIC Educational Resources Information Center

Beretta, Alan; Davies, Alan

The Bangalore Communicational Teaching Project (CTP) in India operates on the central tenet that in English instruction, form can be acquired through a focus on meaning alone, that a grammatical system can be assimilated unconsciously if the mind is engaged in trying to understand or convey meaning. Linguistic specification is not used in CTP, and…

Genomic Sequence and Characterization of the Virulent Bacteriophage φCTP1 from Clostridium tyrobutyricum and Heterologous Expression of Its Endolysin▿

PubMed Central

Mayer, Melinda J.; Payne, John; Gasson, Michael J.; Narbad, Arjan

2010-01-01

The growth of Clostridium tyrobutyricum in developing cheese leads to spoilage and cheese blowing. Bacteriophages or their specific lytic enzymes may provide a biological control method for eliminating such undesirable organisms without affecting other microflora. We isolated the virulent bacteriophage φCTP1 belonging to the Siphoviridae and have shown that it is effective in causing lysis of sensitive strains. The double-stranded DNA genome of φCTP1 is 59,199 bp, and sequence analysis indicated that it has 86 open reading frames. orf29 was identified as the gene coding for the phage endolysin responsible for cell wall degradation prior to virion release. We cloned and expressed the ctp1l gene in E. coli and demonstrated that the partially purified protein induced lysis of C. tyrobutyricum cells and reduced viable counts both in buffer and in milk. The endolysin was inactive against a range of clostridial species but did show lysis of Clostridium sporogenes, another potential spoilage organism. Removal of the C-terminal portion of the endolysin completely abolished lytic activity. PMID:20581196

La-CTP: Loop-Aware Routing for Energy-Harvesting Wireless Sensor Networks.

PubMed

Sun, Guodong; Shang, Xinna; Zuo, Yan

2018-02-02

In emerging energy-harvesting wireless sensor networks (EH-WSN), the sensor nodes can harvest environmental energy to drive their operation, releasing the user's burden in terms of frequent battery replacement, and even enabling perpetual sensing systems. In EH-WSN applications, usually, the node in energy-harvesting or recharging state has to stop working until it completes the energy replenishment. However, such temporary departures of recharging nodes severely impact the packet routing, and one immediate result is the routing loop problem. Controlling loops in connectivity-intermittent EH-WSN in an efficient way is a big challenge in practice, and so far, users still lack of effective and practicable routing protocols with loop handling. Based on the Collection Tree Protocol (CTP) widely used in traditional wireless sensor networks, this paper proposes a loop-aware routing protocol for real-world EH-WSNs, called La-CTP, which involves a new parent updating metric and a proactive, adaptive beaconing scheme to effectively suppress the occurrence of loops and unlock unavoidable loops, respectively. We constructed a 100-node testbed to evaluate La-CTP, and the experimental results showed its efficacy and efficiency.

Use of MODIS Cloud Top Pressure to Improve Assimilation Yields of AIRS Radiances in GSI

NASA Technical Reports Server (NTRS)

Zavodsky, Bradley; Srikishen, Jayanthi

2014-01-01

Improvements to global and regional numerical weather prediction have been demonstrated through assimilation of data from NASA's Atmospheric Infrared Sounder (AIRS). Current operational data assimilation systems use AIRS radiances, but impact on regional forecasts has been much smaller than for global forecasts. Previously, it has been shown that cloud top designation associated with quality control procedures within the Gridpoint Statistical Interpolation (GSI) system used operationally by a number of Joint Center for Satellite Data Assimilation (JCSDA) partners may not provide the best representation of cloud top pressure (CTP). Because this designated CTP determines which channels are cloud-free and, thus, available for assimilation, ensuring the most accurate representation of this value is imperative to obtaining the greatest impact from satellite radiances. This paper examines the assimilation of hyperspectral sounder data used in operational numerical weather prediction by comparing analysis increments and numerical forecasts generated using operational techniques with a research technique that swaps CTP from the Moderate-resolution Imaging Spectroradiometer (MODIS) for the value of CTP calculated from the radiances within GSI.

Current status of biosimilars in the treatment of inflammatory bowel diseases

PubMed Central

2016-01-01

Introduction of biological therapies have led to dramatic changes in the management of debilitating immune-mediated inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease. However, the long term use of these agents may be very expensive, placing a significant burden on National Healthcare Systems. The development of first biosimilar to infliximab, CT-P13 (Remsima; Celltrion Inc., Incheon, Korea and Inflextra; Hospiral, Lake Forest, Illinois, USA) has become another way to decrease the medical care cost and increase patient treatment option, but, actual equivalence of efficacy and safety of CT-P13 was investigated in rheumatic diseases only. The extrapolation of outcome from rheumatic trials to IBD and the interchangeability of CT-P13 with infliximab have come to be a matter of concern. Two recent retrospective studies reported the similarity of CT-P13 in terms of efficacy and safety. Infliximab biosimilars may be promising new treatment options for IBD patients, however, well-designed, prospective randomized non-inferiority trials should be needed to confidently integrate infliximab biosimilars into IBD treatment. PMID:26884730

Shortened Mean Transit Time in CT Perfusion With Singular Value Decomposition Analysis in Acute Cerebral Infarction: Quantitative Evaluation and Comparison With Various CT Perfusion Parameters.

PubMed

Murayama, Kazuhiro; Katada, Kazuhiro; Hayakawa, Motoharu; Toyama, Hiroshi

We aimed to clarify the cause of shortened mean transit time (MTT) in acute ischemic cerebrovascular disease and examined its relationship with reperfusion. Twenty-three patients with acute ischemic cerebrovascular disease underwent whole-brain computed tomography perfusion (CTP). The maximum MTT (MTTmax), minimum MTT (MTTmin), ratio of maximum and minimum MTT (MTTmin/max), and minimum cerebral blood volume (CBV) (CBVmin) were measured by automatic region of interest analysis. Diffusion weighted image was performed to calculate infarction volume. We compared these CTP parameters between reperfusion and nonreperfusion groups and calculated correlation coefficients between the infarction core volume and CTP parameters. Significant differences were observed between reperfusion and nonreperfusion groups (MTTmin/max: P = 0.014; CBVmin ratio: P = 0.038). Regression analysis of CTP and high-intensity volume on diffusion weighted image showed negative correlation (CBVmin ratio: r = -0.41; MTTmin/max: r = -0.30; MTTmin ratio: r = -0.27). A region of shortened MTT indicated obstructed blood flow, which was attributed to the singular value decomposition method error.

Childhood Arthritis and Rheumatology Research Alliance Consensus Clinical Treatment Plans for Juvenile Dermatomyositis with Persistent Skin Rash.

PubMed

Huber, Adam M; Kim, Susan; Reed, Ann M; Carrasco, Ruy; Feldman, Brian M; Hong, Sandy D; Kahn, Philip; Rahimi, Homaira; Robinson, Angela Byun; Vehe, Richard K; Weiss, Jennifer E; Spencer, Charles

2017-01-01

Juvenile dermatomyositis (JDM) is the most common form of idiopathic inflammatory myopathy in children. While outcomes are generally thought to be good, persistence of skin rash is a common problem. The goal of this study was to describe the development of clinical treatment plans (CTP) for children with JDM characterized by persistent skin rash despite complete resolution of muscle involvement. The Childhood Arthritis and Rheumatology Research Alliance, a North American consortium of pediatric rheumatologists and other healthcare providers, used a combination of Delphi surveys and nominal group consensus meetings to develop CTP that reflected consensus on typical treatments for patients with JDM with persistent skin rash. Consensus was reached on patient characteristics and outcome assessment. Patients should have previously received corticosteroids and methotrexate (MTX). Three consensus treatment plans were developed. Plan A added intravenous immunoglobulin (IVIG) if it was not already being used. Plan B added mycophenolate mofetil, while Plan C added cyclosporine. Continuation of previous treatments, including corticosteroids, MTX, and IVIG, was permitted in plans B and C. Three consensus CTP were developed for use in children with JDM and persistent skin rash despite complete resolution of muscle disease. These CTP reflect typical treatment approaches and are not to be considered treatment recommendations or standard of care. Using prospective data collection and statistical methods to account for nonrandom treatment assignment, it is expected that these CTP will be used to allow treatment comparisons, and ultimately determine the best treatment for these patients.

Membrane penetrating peptides greatly enhance baculovirus transduction efficiency into mammalian cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Hong-Zhang; Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan, ROC; Wu, Carol P.

2011-02-11

Research highlights: {yields} Ligation of CTP with GP64 enhances baculovirus transduction into mammalian cells. {yields} Fusion of PTD with VP39 enhances baculovirus transduction into mammalian cells. {yields} CTP and PTD-carrying viruses improve the transduction of co-transduced baculoviruses. {yields} Virus entry and gene expression can be separate events in different cell types. -- Abstract: The baculovirus group of insect viruses is widely used for foreign gene introduction into mammalian cells for gene expression and protein production; however, the efficiency of baculovirus entry into mammalian cells is in general still low. In this study, two recombinant baculoviruses were engineered and their abilitymore » to improve viral entry was examined: (1) cytoplasmic transduction peptide (CTP) was fused with baculovirus envelope protein, GP64, to produce a cytoplasmic membrane penetrating baculovirus (vE-CTP); and (2) the protein transduction domain (PTD) of HIV TAT protein was fused with the baculovirus capsid protein VP39 to form a nuclear membrane penetrating baculovirus (vE-PTD). Transduction experiments showed that both viruses had better transduction efficiency than vE, a control virus that only expresses EGFP in mammalian cells. Interestingly, vE-CTP and vE-PTD were also able to improve the transduction efficiency of a co-transduced baculovirus, resulting in higher levels of gene expression. Our results have described new routes to further enhance the development of baculovirus as a tool for gene delivery into mammalian cells.« less

Computed Tomographic Perfusion Predicts Poor Outcomes in a Randomized Trial of Endovascular Therapy.

PubMed

Wannamaker, Robert; Guinand, Taurian; Menon, Bijoy K; Demchuk, Andrew; Goyal, Mayank; Frei, Donald; Bharatha, Aditya; Jovin, Tudor G; Shankar, Jai; Krings, Timo; Baxter, Blaise; Holmstedt, Christine; Swartz, Richard; Dowlatshahi, Dar; Chan, Richard; Tampieri, Donatella; Choe, Hana; Burns, Paul; Gentile, Nina; Rempel, Jeremy; Shuaib, Ashfaq; Buck, Brian; Bivard, Andrew; Hill, Michael; Butcher, Kenneth

2018-06-01

In the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), patients with large vessel occlusions and small infarct cores identified with computed tomography (CT)/CT angiography were randomized to endovascular therapy or standard of care. CT perfusion (CTP) was obtained in some cases but was not used to select patients. We tested the hypothesis that patients with penumbral CTP patterns have higher rates of good clinical outcome. All CTP data acquired in ESCAPE patients were analyzed centrally using a semiautomated perfusion threshold-based approach. A penumbral pattern was defined as an infarct core <70 mL, penumbral volume >15 mL, and a total hypoperfused volume:core volume ratio of >1.8. The primary outcome was good functional outcome at 90 days (modified Rankin Scale score, 0-2). CTP was acquired in 138 of 316 ESCAPE patients. Penumbral patterns were present in 116 of 128 (90.6%) of patients with interpretable CTP data. The rate of good functional outcome in penumbral pattern patients (53 of 114; 46%) was higher than that in nonpenumbral patients (2 of 12; 17%; P =0.041). In penumbral patients, endovascular therapy increased the likelihood of a good clinical outcome (34 of 58; 57%) compared with those in the control group (19 of 58; 33%; odds ratio, 2.68; 95% confidence interval, 1.25-5.76; P =0.011). Only 3 of 12 nonpenumbral patients were randomized to the endovascular group, preventing an analysis of treatment effect. The majority of patients with CTP imaging in the ESCAPE trial had penumbral patterns, which were associated with better outcomes overall. Patients with penumbra treated with endovascular therapy had the greatest odds of good functional outcome. Nonpenumbral patients were much less likely to achieve good outcomes. © 2018 American Heart Association, Inc.

Effect of increasing the sampling interval to 2 seconds on the radiation dose and accuracy of CT perfusion of the head and neck.

PubMed

Tawfik, Ahmed M; Razek, Ahmed A; Elhawary, Galal; Batouty, Nihal M

2014-01-01

To evaluate the effect of increasing the sampling interval from 1 second (1 image per second) to 2 seconds (1 image every 2 seconds) on computed tomographic (CT) perfusion (CTP) of head and neck tumors. Twenty patients underwent CTP studies of head and neck tumors with images acquired in cine mode for 50 seconds using sampling interval of 1 second. Using deconvolution-based software, analysis of CTP was done with sampling interval of 1 second and then 2 seconds. Perfusion maps representing blood flow, blood volume, mean transit time, and permeability surface area product (PS) were obtained. Quantitative tumor CTP values were compared between the 2 sampling intervals. Two blinded radiologists compared the subjective quality of CTP maps using a 3-point scale between the 2 sampling intervals. Radiation dose parameters were recorded for the 2 sampling interval rates. No significant differences were observed between the means of the 4 perfusion parameters generated using both sampling intervals; all P >0.05. The 95% limits of agreement between the 2 sampling intervals were -65.9 to 48.1) mL/min per 100 g for blood flow, -3.6 to 3.1 mL/100 g for blood volume, -2.9 to 3.8 seconds for mean transit time, and -10.0 to 12.5 mL/min per 100 g for PS. There was no significant difference between the subjective quality scores of CTP maps obtained using the 2 sampling intervals; all P > 0.05. Radiation dose was halved when sampling interval increased from 1 to 2 seconds. Increasing the sampling interval rate to 1 image every 2 seconds does not compromise the image quality and has no significant effect on quantitative perfusion parameters of head and neck tumors. The radiation dose is halved.

The influence of early psychosocial intervention on the long-term clinical outcomes of people suffering from schizophrenia.

PubMed

Cechnicki, Andrzej; Bielańska, Anna

2017-02-26

To compare the treatment outcomes of DSM-IV-TR schizophrenia patients in either a Community Treatment Program or an Individual Treatment Program (CTP vs. ITP). The assessment was made after the first hospitalization, and then after three and twelve years. Participants were randomly assigned to CTP (experimental) and ITP (traditional) group, with 40 people in each group. 67 people (84%) participated in all three assessments. The socio-demographic and clinical indicators were the same for both groups. In the first three years only the CTP group participated in day-care treatment, patient and family psychoeducation and community treatment. Later, both groups received this treatment. The following tools were used: Anamnestic and Catamnestic Questionnaire, the GAF scale, the BPRS LA and Lehman's Quality of Life Interview. It was only after twelve years that there was a significant beneficial improvement in the mean GAF score in the CTP group (p = 0.036), which was comparable with the results obtained by Watt and Shepherd for the course of the illness in favorable remission cases (p = 0.038). The difference in the number of relapses was also significantly in favor of the CTP group only after 12 years (p = 0.045), as was the difference in the number of rehospitalizations (p = 0.013). The general severity of symptoms was found to be significantly lower for the CPT group after 3 (p = 0.008) and 12 years (p = 0.030), whereas it was significantly lower in the case of positive syndrome only after 3 years (p = 0.044). 1. A greater number of favorable differences were identified for the CTP group at the twelve-year point than at the conclusion of the experiment. 2. The three-year delay in introducing psycho-social treatment was associated with a poorer long-term outcome for the clinical course of schizophrenia.

Antibodies against a peptide of cholera toxin differing in cross-reactivity with the toxin differ in their specific interactions with the peptide as observed by sup 1 H NMR spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anglister, J.; Zilber, B.

1990-01-30

The interactions between the aromatic residues of the monoclonal antibody TE34, and its peptide antigen CTP3, have been studied by 2D TRNOE difference spectroscopy. The sequence of CTP3 corresponds to residues 50-64 of the B subunit of cholera toxin (VEVPGSQHIDSQKKA). Unlike two previously studied anti-CTP3 antibodies (TE32 and TE33), the TE34 antibody does not bind the toxin. The off-rate of CTP3 from TE34 was found to be too slow to measure strong TRNOE cross-peaks between the antibody and the peptide. Much faster off-rates, resulting in a strong TRNOE, were obtained for two peptide analogues: (a) CTP3 with an amide inmore » the C-terminus (VEVPGSQHIDSQKKA-NH{sub 2}) and (b) a truncated version of the peptide (N-acetyl-IDSQKKA). These modifications do not interfere significantly either with the interactions of the unmodified part of the peptide with the antibody or with intramolecular interactions occurring in the epitope recognized by the antibody. The combined use of these peptides allows us to study the interactions between the antibody and the whole peptide. Two tyrosine residues and one or more tryptophan and phenylalanine residues have been found to interact with histidine-8, isoleucine-9, aspartate-10, lysine-13 and/or lysine-14, and alanine-15 of the peptide. The strong interaction of TE34 with the negatively charged C-terminus of CTP3 is one of the main reasons for its lack of cross-reactivity with the native toxin. Similar use of modified peptides may extend the applicability of 2D TRNOE difference spectroscopy to the study of other antibody-peptide complexes involving slow peptide off-rates.« less

Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase ι.

PubMed

Choi, Jeong-Yun; Patra, Amritaj; Yeom, Mina; Lee, Young-Sam; Zhang, Qianqian; Egli, Martin; Guengerich, F Peter

2016-09-30

DNA polymerase (pol) ι is a Y-family polymerase involved in translesion synthesis, exhibiting higher catalytic activity with Mn 2+ than Mg 2+ The human germline R96G variant impairs both Mn 2+ -dependent and Mg 2+ -dependent activities of pol ι, whereas the Δ1-25 variant selectively enhances its Mg 2+ -dependent activity. We analyzed pre-steady-state kinetic and structural effects of these two metal ions and genetic variations on pol ι using pol ι core (residues 1-445) proteins. The presence of Mn 2+ (0.15 mm) instead of Mg 2+ (2 mm) caused a 770-fold increase in efficiency (k pol /K d ,dCTP ) of pol ι for dCTP insertion opposite G, mainly due to a 450-fold decrease in K d ,dCTP The R96G and Δ1-25 variants displayed a 53-fold decrease and a 3-fold increase, respectively, in k pol /K d ,dCTP for dCTP insertion opposite G with Mg 2+ when compared with wild type, substantially attenuated by substitution with Mn 2+ Crystal structures of pol ι ternary complexes, including the primer terminus 3'-OH and a non-hydrolyzable dCTP analogue opposite G with the active-site Mg 2+ or Mn 2+ , revealed that Mn 2+ achieves more optimal octahedral coordination geometry than Mg 2+ , with lower values in average coordination distance geometry in the catalytic metal A-site. Crystal structures of R96G revealed the loss of three H-bonds of residues Gly-96 and Tyr-93 with an incoming dNTP, due to the lack of an arginine, as well as a destabilized Tyr-93 side chain secondary to the loss of a cation-π interaction between both side chains. These results provide a mechanistic basis for alteration in pol ι catalytic function with coordinating metals and genetic variation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase ι*

PubMed Central

Choi, Jeong-Yun; Patra, Amritaj; Yeom, Mina; Lee, Young-Sam; Zhang, Qianqian; Egli, Martin; Guengerich, F. Peter

2016-01-01

DNA polymerase (pol) ι is a Y-family polymerase involved in translesion synthesis, exhibiting higher catalytic activity with Mn2+ than Mg2+. The human germline R96G variant impairs both Mn2+-dependent and Mg2+-dependent activities of pol ι, whereas the Δ1–25 variant selectively enhances its Mg2+-dependent activity. We analyzed pre-steady-state kinetic and structural effects of these two metal ions and genetic variations on pol ι using pol ι core (residues 1–445) proteins. The presence of Mn2+ (0.15 mm) instead of Mg2+ (2 mm) caused a 770-fold increase in efficiency (kpol/Kd,dCTP) of pol ι for dCTP insertion opposite G, mainly due to a 450-fold decrease in Kd,dCTP. The R96G and Δ1–25 variants displayed a 53-fold decrease and a 3-fold increase, respectively, in kpol/Kd,dCTP for dCTP insertion opposite G with Mg2+ when compared with wild type, substantially attenuated by substitution with Mn2+. Crystal structures of pol ι ternary complexes, including the primer terminus 3′-OH and a non-hydrolyzable dCTP analogue opposite G with the active-site Mg2+ or Mn2+, revealed that Mn2+ achieves more optimal octahedral coordination geometry than Mg2+, with lower values in average coordination distance geometry in the catalytic metal A-site. Crystal structures of R96G revealed the loss of three H-bonds of residues Gly-96 and Tyr-93 with an incoming dNTP, due to the lack of an arginine, as well as a destabilized Tyr-93 side chain secondary to the loss of a cation-π interaction between both side chains. These results provide a mechanistic basis for alteration in pol ι catalytic function with coordinating metals and genetic variation. PMID:27555320

Limited reliability of computed tomographic perfusion acute infarct volume measurements compared with diffusion-weighted imaging in anterior circulation stroke.

PubMed

Schaefer, Pamela W; Souza, Leticia; Kamalian, Shervin; Hirsch, Joshua A; Yoo, Albert J; Kamalian, Shahmir; Gonzalez, R Gilberto; Lev, Michael H

2015-02-01

Diffusion-weighted imaging (DWI) can reliably identify critically ischemic tissue shortly after stroke onset. We tested whether thresholded computed tomographic cerebral blood flow (CT-CBF) and CT-cerebral blood volume (CT-CBV) maps are sufficiently accurate to substitute for DWI for estimating the critically ischemic tissue volume. Ischemic volumes of 55 patients with acute anterior circulation stroke were assessed on DWI by visual segmentation and on CT-CBF and CT-CBV with segmentation using 15% and 30% thresholds, respectively. The contrast:noise ratios of ischemic regions on the DWI and CT perfusion (CTP) images were measured. Correlation and Bland-Altman analyses were used to assess the reliability of CTP. Mean contrast:noise ratios for DWI, CT-CBF, and CT-CBV were 4.3, 0.9, and 0.4, respectively. CTP and DWI lesion volumes were highly correlated (R(2)=0.87 for CT-CBF; R(2)=0.83 for CT-CBV; P<0.001). Bland-Altman analyses revealed little systemic bias (-2.6 mL) but high measurement variability (95% confidence interval, ±56.7 mL) between mean CT-CBF and DWI lesion volumes, and systemic bias (-26 mL) and high measurement variability (95% confidence interval, ±64.0 mL) between mean CT-CBV and DWI lesion volumes. A simulated treatment study demonstrated that using CTP-CBF instead of DWI for detecting a statistically significant effect would require at least twice as many patients. The poor contrast:noise ratios of CT-CBV and CT-CBF compared with those of DWI result in large measurement error, making it problematic to substitute CTP for DWI in selecting individual acute stroke patients for treatment. CTP could be used for treatment studies of patient groups, but the number of patients needed to identify a significant effect is much higher than the number needed if DWI is used. © 2014 American Heart Association, Inc.

Validation of motion correction techniques for liver CT perfusion studies

PubMed Central

Chandler, A; Wei, W; Anderson, E F; Herron, D H; Ye, Z; Ng, C S

2012-01-01

Objectives Motion in images potentially compromises the evaluation of temporally acquired CT perfusion (CTp) data; image registration should mitigate this, but first requires validation. Our objective was to compare the relative performance of manual, rigid and non-rigid registration techniques to correct anatomical misalignment in acquired liver CTp data sets. Methods 17 data sets in patients with liver tumours who had undergone a CTp protocol were evaluated. Each data set consisted of a cine acquisition during a breath-hold (Phase 1), followed by six further sets of cine scans (each containing 11 images) acquired during free breathing (Phase 2). Phase 2 images were registered to a reference image from Phase 1 cine using two semi-automated intensity-based registration techniques (rigid and non-rigid) and a manual technique (the only option available in the relevant vendor CTp software). The performance of each technique to align liver anatomy was assessed by four observers, independently and blindly, on two separate occasions, using a semi-quantitative visual validation study (employing a six-point score). The registration techniques were statistically compared using an ordinal probit regression model. Results 306 registrations (2448 observer scores) were evaluated. The three registration techniques were significantly different from each other (p=0.03). On pairwise comparison, the semi-automated techniques were significantly superior to the manual technique, with non-rigid significantly superior to rigid (p<0.0001), which in turn was significantly superior to manual registration (p=0.04). Conclusion Semi-automated registration techniques achieved superior alignment of liver anatomy compared with the manual technique. We hope this will translate into more reliable CTp analyses. PMID:22374283

Computed Tomography Perfusion Improves Diagnostic Accuracy in Acute Posterior Circulation Stroke.

PubMed

Sporns, Peter; Schmidt, Rene; Minnerup, Jens; Dziewas, Rainer; Kemmling, André; Dittrich, Ralf; Zoubi, Tarek; Heermann, Philipp; Cnyrim, Christian; Schwindt, Wolfram; Heindel, Walter; Niederstadt, Thomas; Hanning, Uta

2016-01-01

Computed tomography perfusion (CTP) has a high diagnostic value in the detection of acute ischemic stroke in the anterior circulation. However, the diagnostic value in suspected posterior circulation (PC) stroke is uncertain, and whole brain volume perfusion is not yet in widespread use. We therefore studied the additional value of whole brain volume perfusion to non-contrast CT (NCCT) and CT angiography source images (CTA-SI) for infarct detection in patients with suspected acute ischemic PC stroke. This is a retrospective review of patients with suspected stroke in the PC in a database of our stroke center (n = 3,011) who underwent NCCT, CTA and CTP within 9 h after stroke onset and CT or MRI on follow-up. Images were evaluated for signs and pc-ASPECTS locations of ischemia. Three imaging models - A (NCCT), B (NCCT + CTA-SI) and C (NCCT + CTA-SI + CTP) - were compared with regard to the misclassification rate relative to gold standard (infarction in follow-up imaging) using the McNemar's test. Of 3,011 stroke patients, 267 patients had a suspected stroke in the PC and 188 patients (70.4%) evidenced a PC infarct on follow-up imaging. The sensitivity of Model C (76.6%) was higher compared with that of Model A (21.3%) and Model B (43.6%). CTP detected significantly more ischemic lesions, especially in the cerebellum, posterior cerebral artery territory and thalami. Our findings in a large cohort of consecutive patients show that CTP detects significantly more ischemic strokes in the PC than CTA and NCCT alone. © 2016 S. Karger AG, Basel.

Safe use of proton pump inhibitors in patients with cirrhosis.

PubMed

Weersink, Rianne A; Bouma, Margriet; Burger, David M; Drenth, Joost P H; Froukje Harkes-Idzinga, S; Hunfeld, Nicole G M; Metselaar, Herold J; Monster-Simons, Margje H; van Putten, Sandra A W; Taxis, Katja; Borgsteede, Sander D

2018-04-24

Proton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in cirrhosis. A systematic literature search identified studies about the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child-Turcotte-Pugh (CTP) classification. A total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having 'no additional risks known'. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole in a maximum dosage of 20 mg per day. Pantoprazole and lansoprazole were classified as unsafe, because of 4- to 8-fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered. We suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients. This article is protected by copyright. All rights reserved.

CTP synthase 1, a smooth muscle-sensitive therapeutic target for effective vascular repair

PubMed Central

Tang, Rui; Cui, Xiao-Bing; Wang, Jia-Ning; Chen, Shi-You

2013-01-01

Objective Vascular remodeling due to smooth muscle cell (SMC) proliferation and neointima formation is a major medical challenge in cardiovascular intervention. However, anti-neointima drugs often indistinguishably block re-endothelialization, an essential step toward successful vascular repair, due to their non-specific effect on endothelial cells (EC). The objective of this study was to identify a therapeutic target that differentially regulates SMC and EC proliferation. Approach and Results By using both rat balloon-injury and mouse wire-injury models, we identified CTP synthase (CTPS) as one of the potential targets that may be used for developing therapeutics for treating neointima-related disorders. CTPS1 was induced in proliferative SMCs in vitro and neointima SMCs in vivo. Blockade of CTPS1 expression by small hairpin RNA or activity by cyclopentenyl cytosine suppressed SMC proliferation and neointima formation. Surprisingly, cyclopentenyl cytosine had much less effect on EC proliferation. Of importance, blockade of CTPS1 in vivo sustained the re-endothelialization due to induction of CTP synthesis salvage pathway enzymes nucleoside diphosphate kinase A and B in ECs. Diphosphate kinase B appeared to preserve EC proliferation via utilization of extracellular cytidine to synthesize CTP. Indeed, blockade of both CTPS1 and diphosphate kinase B suppressed EC proliferation in vitro and the re-endothelization in vivo. Conclusions Our study uncovered a fundamental difference in CTP biosynthesis between SMCs and ECs during vascular remodeling, which provided a novel strategy by using cyclopentenyl cytosine or other CTPS1 inhibitors to selectively block SMC proliferation without disturbing or even promoting re-endothelialization for effective vascular repair following injury. PMID:24008161

Collision and phonation threshold pressures before and after loud, prolonged vocalization in trained and untrained voices.

PubMed

Enflo, Laura; Sundberg, Johan; McAllister, Anita

2013-09-01

The phonation threshold pressure (PTP) is defined as the lowest subglottal pressure needed for obtaining and sustaining vocal fold oscillation. It has been found to increase during vocal fatigue. In the present study, PTP is measured together with the threshold pressure needed for vocal fold collision; henceforth, the collision threshold pressure (CTP). PTP and CTP are compared before and after loud, prolonged vocalization in singer and nonsinger voices. Ten subjects repeated the vowel sequence /a, e, i, o, u/ at a Sound Pressure Level of at least 80 dB at 0.3 m for 20 minutes. Audio and electroglottography signals were recorded before and after this exercise. At the same time, oral pressure was registered while the subjects produced a diminuendo repeating the syllable /pa:/, thus acquiring an approximate of the subglottal pressure. CTP and PTP increased significantly after the vocal loading in the nonsinger subjects. On the other hand, singers reported no substantial effect of the exercise, and most singers had a mean after-to-before ratio close to 1 for both CTP and PTP. Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

La-CTP: Loop-Aware Routing for Energy-Harvesting Wireless Sensor Networks

PubMed Central

Sun, Guodong; Shang, Xinna; Zuo, Yan

2018-01-01

In emerging energy-harvesting wireless sensor networks (EH-WSN), the sensor nodes can harvest environmental energy to drive their operation, releasing the user’s burden in terms of frequent battery replacement, and even enabling perpetual sensing systems. In EH-WSN applications, usually, the node in energy-harvesting or recharging state has to stop working until it completes the energy replenishment. However, such temporary departures of recharging nodes severely impact the packet routing, and one immediate result is the routing loop problem. Controlling loops in connectivity-intermittent EH-WSN in an efficient way is a big challenge in practice, and so far, users still lack of effective and practicable routing protocols with loop handling. Based on the Collection Tree Protocol (CTP) widely used in traditional wireless sensor networks, this paper proposes a loop-aware routing protocol for real-world EH-WSNs, called La-CTP, which involves a new parent updating metric and a proactive, adaptive beaconing scheme to effectively suppress the occurrence of loops and unlock unavoidable loops, respectively. We constructed a 100-node testbed to evaluate La-CTP, and the experimental results showed its efficacy and efficiency. PMID:29393876

Kinetic Basis of Nucleotide Selection Employed by a Protein Template-Dependent DNA Polymerase†

PubMed Central

Brown, Jessica A.; Fowler, Jason D.; Suo, Zucai

2010-01-01

Rev1, a Y-family DNA polymerase, contributes to spontaneous and DNA damage-induced mutagenic events. In this paper, we have employed pre-steady state kinetic methodology to establish a kinetic basis for nucleotide selection by human Rev1, a unique nucleotidyl transferase that uses a protein template-directed mechanism to preferentially instruct dCTP incorporation. This work demonstrated that the high incorporation efficiency of dCTP is dependent on both substrates: an incoming dCTP and a templating base dG. The extremely low base substitution fidelity of human Rev1 (100 to 10-5) was due to the preferred misincorporation of dCTP with templating bases dA, dT, and dC over correct dNTPs. Using non-natural nucleotide analogs, we showed that hydrogen bonding interactions between residue R357 of human Rev1 and an incoming dNTP are not essential for DNA synthesis. Lastly, human Rev1 discriminates between ribonucleotides and deoxyribonucleotides mainly by reducing the rate of incorporation, and the sugar selectivity of human Rev1 is sensitive to both the size and orientation of the 2′-substituent of a ribonucleotide. PMID:20518555

CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial.

PubMed

Stebbing, Justin; Baranau, Yauheni; Baryash, Valeriy; Manikhas, Alexey; Moiseyenko, Vladimir; Dzagnidze, Giorgi; Zhavrid, Edvard; Boliukh, Dmytro; Stroyakovskii, Daniil; Pikiel, Joanna; Eniu, Alexandru; Komov, Dmitry; Morar-Bolba, Gabriela; Li, Rubi K; Rusyn, Andriy; Lee, Sang Joon; Lee, Sung Young; Esteva, Francisco J

2017-07-01

CT-P6 is a proposed biosimilar to reference trastuzumab. In this study, we aimed to establish equivalence of CT-P6 to reference trastuzumab in neoadjuvant treatment of HER2-positive early-stage breast cancer. In this randomised, double-blind, active-controlled, phase 3 equivalence trial, we recruited women aged 18 years or older with stage I-IIIa operable HER2-positive breast cancer from 112 centres in 23 countries. Inclusion criteria were an Eastern Cooperative Oncology Group performance status score of 0 or 1; a normal left ventricular ejection fraction of at least 55%; adequate bone marrow, hepatic, and renal function; at least one measureable lesion; and known oestrogen and progesterone receptor status. Exclusion criteria included bilateral breast cancer, previous breast cancer treatment, previous anthracycline treatment, and pregnancy or lactation. We randomly allocated patients 1:1 to receive neoadjuvant CT-P6 or reference trastuzumab intravenously (eight cycles, each lasting 3 weeks, for 24 weeks; 8 mg/kg on day 1 of cycle 1 and 6 mg/kg on day 1 of cycles 2-8) in conjunction with neoadjuvant docetaxel (75 mg/m 2 on day 1 of cycles 1-4) and FEC (fluorouracil [500 mg/m 2 ], epirubicin [75 mg/m 2 ], and cyclophosphamide [500 mg/m 2 ]; day 1 of cycles 5-8) therapy. We stratified randomisation by clinical stage, receptor status, and country and used permuted blocks. We did surgery within 3-6 weeks of the final neoadjuvant study drug dose, followed by an adjuvant treatment period of up to 1 year. We monitored long-term safety and efficacy for 3 years after the last patient was enrolled. Participants and investigators were masked to treatment until study completion. The primary efficacy endpoint, analysed in the per-protocol population, was pathological complete response, assessed via specimens obtained during surgery, analysed by masked central review of local histopathology reports. The equivalence margin was -0·15 to 0·15. This trial is registered with ClinicalTrials.gov, number NCT02162667, and is ongoing, but no longer recruiting. Between Aug 7, 2014, and May 6, 2016, we randomly allocated 549 patients (271 [49%] to CT-P6 vs 278 [51%] to reference trastuzumab). A similar proportion of patients achieved pathological complete response with CT-P6 (116 [46·8%; 95% CI 40·4-53·2] of 248 patients) and reference trastuzumab (129 [50·4%; 44·1-56·7] of 256 patients). The 95% CI of the estimated treatment outcome difference (-0·04% [95% CI -0·12 to 0·05]) was within the equivalence margin. 19 (7%) of 271 patients in the CT-P6 group reported serious treatment-emergent adverse events versus 22 (8%) of 278 in the reference trastuzumab group; frequent (occurring in more than one patient) serious adverse events were febrile neutropenia (four [1%] vs one [<1%]) and neutropenia (one [<1%] vs two [1%]). Grade 3 or worse treatment-related adverse events occurred in 17 (6%) of 271 patients in the CT-P6 group versus 23 (8%) of 278 in the reference trastuzumab group; the most frequently reported adverse event was neutropenia in ten (4%) versus 14 (5%). CT-P6 showed equivalent efficacy to reference trastuzumab and adverse events were similar. Availability of trastuzumab biosimilars could increase access to this targeted therapy for HER2-positive early-stage cancer. Celltrion Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oral administration of citrus pulp reduces gasrointestinal recovery of orally dosed Escherichia coli F18 in weaned pigs

USDA-ARS?s Scientific Manuscript database

The effects of citrus pulp (CTP), on the immune and cortisol responses to E. coli F18 inoculation and subsequent E. coli recovery were evaluated in newly weaned pigs (23.3 + 1.8 d of age). Barrows were assigned to 1 of 2 treatment groups; with (CTP; n = 15) and without (Control; n = 15) the in-feed ...

Structure-based Mechanism of CMP-2-keto-3-deoxymanno-octulonic Acid Synthetase

PubMed Central

Heyes, Derren J.; Levy, Colin; Lafite, Pierre; Roberts, Ian S.; Goldrick, Marie; Stachulski, Andrew V.; Rossington, Steven B.; Stanford, Deborah; Rigby, Stephen E. J.; Scrutton, Nigel S.; Leys, David

2009-01-01

The enzyme CMP-Kdo synthetase (KdsB) catalyzes the addition of 2-keto-3-deoxymanno-octulonic acid (Kdo) to CTP to form CMP-Kdo, a key reaction in the biosynthesis of lipopolysaccharide. The reaction catalyzed by KdsB and the related CMP-acylneuraminate synthase is unique among the sugar-activating enzymes in that the respective sugars are directly coupled to a cytosine monophosphate. Using inhibition studies, in combination with isothermal calorimetry, we show the substrate analogue 2β-deoxy-Kdo to be a potent competitive inhibitor. The ligand-free Escherichia coli KdsB and ternary complex KdsB-CTP-2β-deoxy-Kdo crystal structures reveal that Kdo binding leads to active site closure and repositioning of the CTP phosphates and associated Mg2+ ion (Mg-B). Both ligands occupy conformations compatible with an Sn2-type attack on the α-phosphate by the Kdo 2-hydroxyl group. Based on strong similarity with DNA/RNA polymerases, both in terms of overall chemistry catalyzed as well as active site configuration, we postulate a second Mg2+ ion (Mg-A) is bound by the catalytically competent KdsB-CTP-Kdo ternary complex. Modeling of this complex reveals the Mg-A coordinated to the conserved Asp100 and Asp235 in addition to the CTP α-phosphate and both the Kdo carboxylic and 2-hydroxyl groups. EPR measurements on the Mn2+-substituted ternary complex support this model. We propose the KdsB/CNS sugar-activating enzymes catalyze the formation of activated sugars, such as the abundant CMP-5-N-acetylneuraminic acid, by recruitment of two Mg2+ to the active site. Although each metal ion assists in correct positioning of the substrates and activation of the α-phosphate, Mg-A is responsible for activation of the sugar-hydroxyl group. PMID:19815542

Transition-state destabilization reveals how human DNA polymerase β proceeds across the chemically unstable lesion N7-methylguanine

PubMed Central

Ouzon-Shubeita, Hala; Lee, Seongmin

2014-01-01

N7-Methyl-2′-deoxyguanosine (m7dG) is the predominant lesion formed by methylating agents. A systematic investigation on the effect of m7dG on DNA replication has been difficult due to the chemical instability of m7dG. To gain insights into the m7dG effect, we employed a 2′-fluorine-mediated transition-state destabilzation strategy. Specifically, we determined kinetic parameters for dCTP insertion opposite a chemically stable m7dG analogue, 2′-fluoro-m7dG (Fm7dG), by human DNA polymerase β (polβ) and solved three X-ray structures of polβ in complex with the templating Fm7dG paired with incoming dCTP or dTTP analogues. The kinetic studies reveal that the templating Fm7dG slows polβ catalysis ∼300-fold, suggesting that m7dG in genomic DNA may impede replication by some DNA polymerases. The structural analysis reveals that Fm7dG forms a canonical Watson–Crick base pair with dCTP, but metal ion coordination is suboptimal for catalysis in the polβ-Fm7dG:dCTP complex, which partially explains the slow insertion of dCTP opposite Fm7dG by polβ. In addition, the polβ-Fm7dG:dTTP structure shows open protein conformations and staggered base pair conformations, indicating that N7-methylation of dG does not promote a promutagenic replication. Overall, the first systematic studies on the effect of m7dG on DNA replication reveal that polβ catalysis across m7dG is slow, yet highly accurate. PMID:24966350

Biased visualization of hypoperfused tissue by computed tomography due to short imaging duration: improved classification by image down-sampling and vascular models.

PubMed

Mikkelsen, Irene Klærke; Jones, P Simon; Ribe, Lars Riisgaard; Alawneh, Josef; Puig, Josep; Bekke, Susanne Lise; Tietze, Anna; Gillard, Jonathan H; Warburton, Elisabeth A; Pedraza, Salva; Baron, Jean-Claude; Østergaard, Leif; Mouridsen, Kim

2015-07-01

Lesion detection in acute stroke by computed-tomography perfusion (CTP) can be affected by incomplete bolus coverage in veins and hypoperfused tissue, so-called bolus truncation (BT), and low contrast-to-noise ratio (CNR). We examined the BT-frequency and hypothesized that image down-sampling and a vascular model (VM) for perfusion calculation would improve normo- and hypoperfused tissue classification. CTP datasets from 40 acute stroke patients were retrospectively analysed for BT. In 16 patients with hypoperfused tissue but no BT, repeated 2-by-2 image down-sampling and uniform filtering was performed, comparing CNR to perfusion-MRI levels and tissue classification to that of unprocessed data. By simulating reduced scan duration, the minimum scan-duration at which estimated lesion volumes came within 10% of their true volume was compared for VM and state-of-the-art algorithms. BT in veins and hypoperfused tissue was observed in 9/40 (22.5%) and 17/40 patients (42.5%), respectively. Down-sampling to 128 × 128 resolution yielded CNR comparable to MR data and improved tissue classification (p = 0.0069). VM reduced minimum scan duration, providing reliable maps of cerebral blood flow and mean transit time: 5 s (p = 0.03) and 7 s (p < 0.0001), respectively). BT is not uncommon in stroke CTP with 40-s scan duration. Applying image down-sampling and VM improve tissue classification. • Too-short imaging duration is common in clinical acute stroke CTP imaging. • The consequence is impaired identification of hypoperfused tissue in acute stroke patients. • The vascular model is less sensitive than current algorithms to imaging duration. • Noise reduction by image down-sampling improves identification of hypoperfused tissue by CTP.

Timing of Occurrence Is the Most Important Characteristic of Spot Sign.

PubMed

Wang, Binli; Yan, Shenqiang; Xu, Mengjun; Zhang, Sheng; Liu, Keqin; Hu, Haitao; Selim, Magdy; Lou, Min

2016-05-01

Most previous studies have used single-phase computed tomographic angiography to detect the spot sign, a marker for hematoma expansion (HE) in spontaneous intracerebral hemorrhage. We investigated whether defining the spot sign based on timing on perfusion computed tomography (CTP) would improve its specificity for predicting HE. We prospectively enrolled supratentorial spontaneous intracerebral hemorrhage patients who underwent CTP within 6 hours of onset. Logistic regression was performed to assess the risk factors for HE and poor outcome. Predictive performance of individual CTP spot sign characteristics were examined with receiver operating characteristic analysis. Sixty-two men and 21 women with spontaneous intracerebral hemorrhage were included in this analysis. Spot sign was detected in 46% (38/83) of patients. Receiver operating characteristic analysis indicated that the timing of spot sign occurrence on CTP had the greatest area under receiver operating characteristic curve for HE (0.794; 95% confidence interval, 0.630-0.958; P=0.007); the cutoff time was 23.13 seconds. On multivariable analysis, the presence of early-occurring spot sign (ie, spot sign before 23.13 seconds) was an independent predictor not only of HE (odds ratio=28.835; 95% confidence interval, 6.960-119.458; P<0.001), but also of mortality at 3 months (odds ratio =22.377; 95% confidence interval, 1.773-282.334; P=0.016). Moreover, the predictive performance showed that the redefined early-occurring spot sign maintained a higher specificity for HE compared with spot sign (91% versus 74%). Redefining the spot sign based on timing of contrast leakage on CTP to determine early-occurring spot sign improves the specificity for predicting HE and 3-month mortality. The use of early-occurring spot sign could improve the selection of ICH patients for potential hemostatic therapy. © 2016 American Heart Association, Inc.

Timing of occurrence is the most important characteristic of spot sign

PubMed Central

Xu, Mengjun; Zhang, Sheng; Liu, Keqin; Hu, Haitao; Selim, Magdy; Lou, Min

2016-01-01

Background and Purpose Most previous studies have used single-phase CT angiography (CTA) to detect the spot sign, a marker for hematoma expansion (HE) in spontaneous intracerebral hemorrhage (SICH). We investigated whether defining the spot sign based on timing on perfusion CT (CTP) would improve its specificity for predicting HE. Methods We prospectively enrolled supratentorial SICH patients, who underwent CTP within 6 h of onset. Logistic regression were performed to assess the risk factors for HE and poor outcome. Predictive performance of individual CTP spot sign characteristics were examined with receiver operating characteristic (ROC) analysis. Results Sixty-two men and 21 women with SICH were included in this analysis. Spot sign was detected in 46% (38/83) patients. ROC analysis indicated that the timing of spot sign occurrence on CTP had the greatest AUC for HE (0.794; 95% CI, 0.630-0.958; P=0.007); the cutoff time was 23.13 seconds. On multivariable analysis, the presence of early-occurring spot sign (EOSS; i.e. spot sign before 23.13 seconds) was an independent predictor, not only of HE (OR=28.835; 95% CI, 6.960-119.458; P<0.001), but also of mortality at 3 months (OR=22.377; 95% CI, 1.773-282.334; P=0.016). Moreover, the predictive performance showed that the redefined EOSS maintained a higher specificity for HE compared to spot sign (91% vs 74%). Conclusions Redefining the spot sign based on timing of contrast leakage on CTP to determine EOSS, improves the specificity for predicting HE and 3-month mortality. The use of EOSS could improve the selection of ICH patients for potential hemostatic therapy. PMID:27026627

Prediction of Post-operative Mortality in Patients with HCV-related Cirrhosis Undergoing Non-Hepatic Surgeries

PubMed Central

Hemida, Khalid; Shabana, Sherif Sadek; Said, Hani; Ali-Eldin, Fatma

2016-01-01

Introduction Patients with chronic liver diseases are at great risk for both morbidity and mortality during the post-operative period due to the stress of surgery and the effects of general anaesthesia. Aim The main aim of this study was to evaluate the value of Model for End-stage Liver Disease (MELD) score, as compared to Child-Turcotte-Pugh (CTP) score, for prediction of 30- day post-operative mortality in Egyptian patients with liver cirrhosis undergoing non-hepatic surgery under general anaesthesia. Materials and Methods A total of 60 patients with Hepatitis C Virus (HCV) - related liver cirrhosis were included in this study. Sensitivity and specificity of MELD and CTP scores were evaluated for the prediction of post-operative mortality. A total of 20 patients who had no clinical, biochemical or radiological evidence of liver disease were included to serve as a control group. Results The highest sensitivity and specificity for detection of post-operative mortality was detected at a MELD score of 13.5. CTP score had a sensitivity of 75%, a specificity of 96.4%, and an overall accuracy of 95% for prediction of post-operative mortality. On the other side and at a cut-off value of 13.5, MELD score had a sensitivity of 100%, a specificity of 64.0%, and an overall accuracy of 66.6% for prediction of post-operative mortality in patients with HCV- related liver cirrhosis. Conclusion MELD score proved to be more sensitive but less specific than CTP score for prediction of post-operative mortality. CTP and MELD scores may be complementary rather than competitive in predicting post-operative mortality in patients with HCV- related liver cirrhosis. PMID:27891371

Evaluating blood-brain barrier permeability in delayed cerebral infarction after aneurysmal subarachnoid hemorrhage.

PubMed

Ivanidze, J; Kesavabhotla, K; Kallas, O N; Mir, D; Baradaran, H; Gupta, A; Segal, A Z; Claassen, J; Sanelli, P C

2015-05-01

Patients with SAH are at increased risk of delayed infarction. Early detection and treatment of delayed infarction remain challenging. We assessed blood-brain barrier permeability, measured as permeability surface area product, by using CTP in patients with SAH with delayed infarction. We performed a retrospective study of patients with SAH with delayed infarction on follow-up NCCT. CTP was performed before the development of delayed infarction. CTP data were postprocessed into permeability surface area product, CBF, and MTT maps. Coregistration was performed to align the infarcted region on the follow-up NCCT with the corresponding location on the CTP maps obtained before infarction. Permeability surface area product, CBF, and MTT values were then obtained in the location of the subsequent infarction. The contralateral noninfarcted region was compared with the affected side in each patient. Wilcoxon signed rank tests were performed to determine statistical significance. Clinical data were collected at the time of CTP and at the time of follow-up NCCT. Twenty-one patients with SAH were included in the study. There was a statistically significant increase in permeability surface area product in the regions of subsequent infarction compared with the contralateral control regions (P < .0001). However, CBF and MTT values were not significantly different in these 2 regions. Subsequent follow-up NCCT demonstrated new delayed infarction in all 21 patients, at which time 38% of patients had new focal neurologic deficits. Our study reveals a statistically significant increase in permeability surface area product preceding delayed infarction in patients with SAH. Further investigation of early permeability changes in SAH may provide new insights into the prediction of delayed infarction. © 2015 by American Journal of Neuroradiology.

Conformation of nanoconfined DNA as a function of ATP, AMP, CTP, Mg2+, and dye binding

NASA Astrophysics Data System (ADS)

Roushan, Maedeh; Riehn, Robert

2014-03-01

DNA molecules stretch in nanochannels with a channel cross-section of 100x100 nm2, thereby allowing analysis by observation of a fluorescent dye. The length and configuration of DNA can be directly observed, and the effect of different DNA-binding proteins on DNA configuration can be studied. Recently, we reported on the ability of T4 ligase to transiently manipulate DNA as a function of ATP and magnesium exposure. In this process we have extensively probed the interactions of dyes and enzyme co-factors with DNA under nanoconfinement. We find negligible effects if DNA is visualized using groove-binding dyes such as DAPI. However, if an intercalating dye (YOYO-1) is used, we find a significant shortening of the DNA in the presence of ATP that we attribute to an interaction of dye and ATP (as well as AMP and CTP). We did not record a noticeable effect due to Mg2+.

Iterative reconstruction for CT perfusion with a prior-image induced hybrid nonlocal means regularization: Phantom studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Bin; Lyu, Qingwen; Ma, Jianhua

2016-04-15

Purpose: In computed tomography perfusion (CTP) imaging, an initial phase CT acquired with a high-dose protocol can be used to improve the image quality of later phase CT acquired with a low-dose protocol. For dynamic regions, signals in the later low-dose CT may not be completely recovered if the initial CT heavily regularizes the iterative reconstruction process. The authors propose a hybrid nonlocal means (hNLM) regularization model for iterative reconstruction of low-dose CTP to overcome the limitation of the conventional prior-image induced penalty. Methods: The hybrid penalty was constructed by combining the NLM of the initial phase high-dose CT inmore » the stationary region and later phase low-dose CT in the dynamic region. The stationary and dynamic regions were determined by the similarity between the initial high-dose scan and later low-dose scan. The similarity was defined as a Gaussian kernel-based distance between the patch-window of the same pixel in the two scans, and its measurement was then used to weigh the influence of the initial high-dose CT. For regions with high similarity (e.g., stationary region), initial high-dose CT played a dominant role for regularizing the solution. For regions with low similarity (e.g., dynamic region), the regularization relied on a low-dose scan itself. This new hNLM penalty was incorporated into the penalized weighted least-squares (PWLS) for CTP reconstruction. Digital and physical phantom studies were performed to evaluate the PWLS-hNLM algorithm. Results: Both phantom studies showed that the PWLS-hNLM algorithm is superior to the conventional prior-image induced penalty term without considering the signal changes within the dynamic region. In the dynamic region of the Catphan phantom, the reconstruction error measured by root mean square error was reduced by 42.9% in PWLS-hNLM reconstructed image. Conclusions: The PWLS-hNLM algorithm can effectively use the initial high-dose CT to reconstruct low-dose CTP in the stationary region while reducing its influence in the dynamic region.« less

Oral administration of citrus pulp reduces gastrointestinal recovery of orally dosed Escherichia coli F18 in weaned pigs

USDA-ARS?s Scientific Manuscript database

The effects of citrus pulp (CTP) on the immune and cortisol responses to E. coli F18 inoculation and subsequent E. coli recovery were evaluated in newly weaned pigs (23.3 + 1.8 d of age). Barrows were assigned to 1 of 2 treatment groups; with (CTP; n = 15) and without (Control; n = 15) the in-feed i...

Serum iron parameters in liver cirrhosis

NASA Astrophysics Data System (ADS)

Siregar, G. A.; Maail, W.

2018-03-01

The liver plays a fundamental role in iron homeostasis. Iron parameters change, especially ferritin, need to be evaluated in patients with liver cirrhosis. Serum ferritin could predict the prognosis of patients with decompensated cirrhosis since it reflects immunemediated and infectious stimuli. Ferritin could express the severity of liver disease and possible subsequent complications. Finally, it might reflect an iron overload condition resulting in significant morbidity and early mortality. 70 patients with decompensated liver cirrhosis divided into three Child-Pugh subgroups. Serum iron parameters include serum iron (SI), total iron binding capacity (TIBC) and ferritin was measured in these groups. From these 70 patients, 30 (42.9%) with HbsAg positive, 26 (37.1%) with anti-HCV positive and 14 (20%) with both HbsAg and anti-HCV positive. Of the 70 patients, 14 (20%) had CTP Class A cirrhosis, 17 (24.3%) had CTP Class B cirrhosis, and 39 (55.7%) had CTP C cirrhosis. The median (range) value of serum iron was 36 (10-345) μg/dl, TIBC was 160 (59-520) μg/dl, Ferritin was 253.5 (8-6078) ng/ml and the transferrin saturation was 22.9 (3.65-216.98) %.We found a significant difference in serum ferritin level with CTP score. Ferritin levels increased as Child-Pugh class progressed (p<0.001).

Detection of Alicyclobacillus species in fruit juice using a random genomic DNA microarray chip.

PubMed

Jang, Jun Hyeong; Kim, Sun-Joong; Yoon, Bo Hyun; Ryu, Jee-Hoon; Gu, Man Bock; Chang, Hyo-Ihl

2011-06-01

This study describes a method using a DNA microarray chip to rapidly and simultaneously detect Alicyclobacillus species in orange juice based on the hybridization of genomic DNA with random probes. Three food spoilage bacteria were used in this study: Alicyclobacillus acidocaldarius, Alicyclobacillus acidoterrestris, and Alicyclobacillus cycloheptanicus. The three Alicyclobacillus species were adjusted to 2 × 10(3) CFU/ml and inoculated into pasteurized 100% pure orange juice. Cy5-dCTP labeling was used for reference signals, and Cy3-dCTP was labeled for target genomic DNA. The molar ratio of 1:1 of Cy3-dCTP and Cy5-dCTP was used. DNA microarray chips were fabricated using randomly fragmented DNA of Alicyclobacillus spp. and were hybridized with genomic DNA extracted from Bacillus spp. Genomic DNA extracted from Alicyclobacillus spp. showed a significantly higher hybridization rate compared with DNA of Bacillus spp., thereby distinguishing Alicyclobacillus spp. from Bacillus spp. The results showed that the microarray DNA chip containing randomly fragmented genomic DNA was specific and clearly identified specific food spoilage bacteria. This microarray system is a good tool for rapid and specific detection of thermophilic spoilage bacteria, mainly Alicyclobacillus spp., and is useful and applicable to the fruit juice industry.

Progress in biosimilar monoclonal antibody development: the infliximab biosimilar CT-P13 in the treatment of rheumatic diseases.

PubMed

Braun, Jürgen; Kudrin, Alex

2015-01-01

Biosimilars are biologic medical products whose active drug substance is made by a living organism or derived from it. The term is used to describe a subsequent version of an innovator biopharmaceutical product aiming at approval following patent expiry on the reference product. Biosimilars of monoclonal need to demonstrate similar but not identical quality of nonclinical and clinical attributes. Not all data of the originator product need to be recapitulated, as large numbers of patient-years of exposure data are already available. Thus, biosimilar development is largely based on the safety profiles of the originator product. The evaluation of biosimilarity includes immunogenicity attributed risks. CT-P13 (Remsima™/Inflectra™, Celltrion/Hospira), a biosimilar of the innovator drug infliximab (INF), was the first approved complex biosimilar monoclonal antibody in the EU, within the framework of WHO, EMA and US FDA biosimilar guidelines. CT-P13 has shown analytical and nonclinical features highly similar to INF including pharmacokinetics, efficacy, safety and immunogenicity profiles in ankylosing spondylitis and rheumatoid arthritis. The objective of this article is to highlight the recent biosimilar development and to review the results from the studies PLANETRA and PLANETAS, which have supported the approval of CT-P13 for several indications.

Identification of CtpL as a chromosomally encoded chemoreceptor for 4-chloroaniline and catechol in Pseudomonas aeruginosa PAO1.

PubMed

Vangnai, Alisa S; Takeuchi, Kazuki; Oku, Shota; Kataoka, Naoya; Nitisakulkan, Tisana; Tajima, Takahisa; Kato, Junichi

2013-12-01

Bacterial chemotaxis influences the ability of bacteria to survive and thrive in most environments, including polluted ones. Despite numerous reports of the phenotypic characterization of chemotactic bacteria, only a few molecular details of chemoreceptors for aromatic pollutants have been described. In this study, the molecular basis of chemotaxis toward an environmentally toxic chlorinated aromatic pollutant, 4-chloroaniline (4CA), was evaluated. Among the three Pseudomonas spp. tested, Pseudomonas aeruginosa PAO1 exhibited positive chemotaxis both to the nonmetabolizable 4CA, where 4-chloroacetanilide was formed as a dead-end transformation product, and to the metabolizable catechol. Molecular analysis of all 26 mutants with a disrupted methyl-accepting chemotaxis gene revealed that CtpL, a chromosomally encoded chemoreceptor, was responsible for the positive chemotactic response toward 4CA. Since CtpL has previously been described to be a major chemoreceptor for inorganic phosphate at low concentrations in PAO1, this report describes a fortuitous ability of CtpL to function toward aromatic pollutants. In addition, its regulation not only was dependent on the presence of the chemoattractant inducer but also was regulated by conditions of phosphate starvation. These results expand the range of known chemotactic transducers and their function in the environmental bacterium PAO1.

An optimized transit peptide for effective targeting of diverse foreign proteins into chloroplasts in rice.

PubMed

Shen, Bo-Ran; Zhu, Cheng-Hua; Yao, Zhen; Cui, Li-Li; Zhang, Jian-Jun; Yang, Cheng-Wei; He, Zheng-Hui; Peng, Xin-Xiang

2017-04-11

Various chloroplast transit peptides (CTP) have been used to successfully target some foreign proteins into chloroplasts, but for other proteins these same CTPs have reduced localization efficiencies or fail completely. The underlying cause of the failures remains an open question, and more effective CTPs are needed. In this study, we initially observed that two E.coli enzymes, EcTSR and EcGCL, failed to be targeted into rice chloroplasts by the commonly-used rice rbcS transit peptide (rCTP) and were subsequently degraded. Further analyses revealed that the N-terminal unfolded region of cargo proteins is critical for their localization capability, and that a length of about 20 amino acids is required to attain the maximum localization efficiency. We considered that the unfolded region may alleviate the steric hindrance produced by the cargo protein, by functioning as a spacer to which cytosolic translocators can bind. Based on this inference, an optimized CTP, named RC2, was constructed. Analyses showed that RC2 can more effectively target diverse proteins, including EcTSR and EcGCL, into rice chloroplasts. Collectively, our results provide further insight into the mechanism of CTP-mediated chloroplastic localization, and more importantly, RC2 can be widely applied in future chloroplastic metabolic engineering, particularly for crop plants.

Crystallization and preliminary X-ray analysis of CTP:phosphoethanolamine cytidylyltransferase (ECT) from Saccharomyces cerevisiae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohtsuka, Jun; Nagata, Koji; Lee, Woo Cheol

2006-10-01

CTP:phosphoethanolamine cytidylyltransferase from S. cerevisiae has been expressed, purified and crystallized. CTP:phosphoethanolamine cytidylyltransferase (ECT) is the enzyme that catalyzes the conversion of phosphoethanolamine to CDP-ethanolamine in the phosphatidylethanolamine-biosynthetic pathway (Kennedy pathway). ECT from Saccharomyces cerevisiae was crystallized by the sitting-drop vapour-diffusion method using PEG 4000 as precipitant. The crystals diffracted X-rays from a synchrotron-radiation source to 1.88 Å resolution. The space group was assigned as primitive tetragonal, P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2, with unit-cell parameters a = b = 66.3, c = 150.8 Å. The crystals contain one ECT molecule in the asymmetric unit (V{sub M} = 2.2more » Å{sup 3} Da{sup −1}), with a solvent content of 43%.« less

Lexical retrieval in discourse: An early indicator of Alzheimer's dementia

PubMed Central

Pekkala, Seija; Wiener, Debra; Himali, Jayandra J.J.; Beiser, Alexa S.; Obler, Loraine K.; Liu, Yulin; McKee, Ann; Auerbach, Sanford; Seshadri, Sudha; Wolf, Philip A.; Au, Rhoda

2014-01-01

We examined the progression of lexical-retrieval deficits in individuals with neuropathologically determined Alzheimer's disease (AD; n = 23) and a comparison group without criteria for AD (n = 24) to determine whether linguistic changes were a significant marker of the disease. Our participants underwent multiple administrations of a neuropsychological battery, with initial administration occurring on average 16 years prior to death. The battery included the Boston Naming Test (BNT), a letter fluency task (FAS), and written description of the Cookie Theft Picture (CTP). Repeated measures analysis revealed that the AD-group showed progressively greater decline in FAS and CTP lexical performance than the comparison group. Cross-sectional time-specific group comparisons indicated that the CTP differentiated performance between the two groups at 7–9 years prior to death and FAS and BNT only at 2–4 years. These results suggest that lexical-retrieval deficits in written discourse serve as an early indicator of AD. PMID:23985011

Lexical retrieval in discourse: an early indicator of Alzheimer's dementia.

PubMed

Pekkala, Seija; Wiener, Debra; Himali, Jayandra J; Beiser, Alexa S; Obler, Loraine K; Liu, Yulin; McKee, Ann; Auerbach, Sanford; Seshadri, Sudha; Wolf, Philip A; Au, Rhoda

2013-12-01

We examined the progression of lexical-retrieval deficits in individuals with neuropathologically determined Alzheimer's disease (AD; n = 23) and a comparison group without criteria for AD (n = 24) to determine whether linguistic changes were a significant marker of the disease. Our participants underwent multiple administrations of a neuropsychological battery, with initial administration occurring on average 16 years prior to death. The battery included the Boston Naming Test (BNT), a letter fluency task (FAS) and written description of the Cookie Theft Picture (CTP). Repeated measures analysis revealed that the AD-group showed progressively greater decline in FAS and CTP lexical performance than the comparison group. Cross-sectional time-specific group comparisons indicated that the CTP differentiated performance between the two groups at 7-9 years prior to death and FAS and BNT only at 2-4 years. These results suggest that lexical-retrieval deficits in written discourse serve as an early indicator of AD.

Assessment of bronchial and pulmonary blood supply in non-small cell lung cancer subtypes using computed tomography perfusion.

PubMed

Nguyen-Kim, Thi Dan Linh; Frauenfelder, Thomas; Strobel, Klaus; Veit-Haibach, Patrick; Huellner, Martin W

2015-03-01

The aim of this study was to investigate the dual blood supply of non-small cell lung cancer (NSCLC) and its association with tumor subtype, size, and stage, using computed tomography perfusion (CTP). A total of 54 patients (median age, 65 years; range, 42-79 years; 15 women, 39 men) with suspected lung cancer underwent a CTP scan of the lung tumor. Pulmonary and bronchial vasculature regions of interest were used to calculate independently CTP parameters (blood flow [BF], blood volume [BV], and mean transit time [MTT]) of the tumor tissue. The mean and maximum pulmonary and bronchial perfusion indexes (PImean and PImax) were calculated. The tumoral volume and the largest tumoral diameter were assessed. Differences in CTP parameters and indexes among NSCLC subtypes, tumor stages and tumor dimensions were analyzed using non-parametric tests. According to biopsy, 37 patients had NSCLC (22 adenocarcinomas [ACs], 8 squamous cell carcinomas [SCCs], 7 large-cell carcinomas [LCC]). The mean bronchial BF/pulmonary BF, bronchial BV/pulmonary BV, and bronchial MTT/pulmonary MTT was 41.2 ± 30.0/36.9 ± 24.2 mL/100 mL/min, 11.4 ± 9.7/10.4 ± 9.4 mL/100 mL, and 11.4 ± 4.3/14.9 ± 4.4 seconds, respectively. In general, higher bronchial BF than pulmonary BF was observed in NSCLC (P = 0.014). Using a tumoral volume cutoff of 3.5 cm, a significant difference in pulmonary PImax was found (P = 0.028). There was a significantly higher mean pulmonary BF in LCCs and SCCs compared with ACs (P = 0.018 and P = 0.044, respectively), whereas the mean bronchial BF was only significantly higher in LCCs compared with ACs (P = 0.024). Correspondingly, the PImax was significantly higher in LCCs and SCCs than in ACs (P = 0.001 for both). Differences between bronchial and pulmonary PImean and PImax among T stages and Union Internationale Contre le Cancer stages were not statistically significant (P values ranging from 0.691 to 0.753). The known dual blood supply of NSCLC, which depends on tumor size and histological subtype, is reflected in CTP parameters, with parameters depending both on tumor size and histological subtype. This has to be accounted for when analyzing NSCLC with CTP.

Diverse heterocyclic scaffolds as dCTP pyrophosphatase 1 inhibitors. Part 1: Triazoles, triazolopyrimidines, triazinoindoles, quinoline hydrazones and arylpiperazines.

PubMed

Llona-Minguez, Sabin; Häggblad, Maria; Martens, Ulf; Throup, Adam; Loseva, Olga; Jemth, Ann-Sofie; Lundgren, Bo; Scobie, Martin; Helleday, Thomas

2017-08-15

A high-throughput screening campaign using a commercial compound library (ChemBridge DiverSET) revealed diverse chemotypes as inhibitors of the human dCTP pyrophosphatase 1 (dCTPase). Triazole, triazolopyrimidine, triazinoindole, quinoline hydrazone and arylpiperazine hits were clustered, confirmed by IC 50 determinations, and their preliminary structure-activity-relationships (SAR) and ligand efficiency scores are discussed in this letter. Copyright © 2017. Published by Elsevier Ltd.

Characterization of a Dopaminergic Stimulatory Factor Derived from Monoclonal Cell Lines of Striatal Origin

DTIC Science & Technology

2006-12-01

other substrates for its biosynthesis would be effective in raising MN9D dopamine content. The pyrimidine, cytidine triphosphate (CTP) reacts with...phosphatidylethanolamine or phosphatidylcholine. MN9D cells were treated for 48 hrs with 2 mM CTP, cytidine diphosphate (CDP) or cytidine monophosphate (CMP), in the...presence or absence of 25 µM ethanolamine or 25 µM phosphoethanolamine. Cytidine alone did not alter the dopaminergic stimulatory effect of

Sugar-modified poly(propylene imine) dendrimers as drug delivery agents for cytarabine to overcome drug resistance.

PubMed

Szulc, Aleksandra; Pulaski, Lukasz; Appelhans, Dietmar; Voit, Brigitte; Klajnert-Maculewicz, Barbara

2016-11-20

Maltose-modified poly(propylene imine) glycodendrimers (PPI-m OS) of the 4th generation provide a promising strategy for leukemia treatment. Anticancer therapy with nucleoside analog drugs such as cytarabine (Ara-C) frequently has limited efficacy due to drug resistance, inefficient uptake and accumulation of the drug inside cancer cells where it has to be transformed into the active triphosphate congener. The cationic nature of PPI dendrimers makes it possible to form complexes with nucleotide Ara-C triphosphate forms (Ara-CTP). The aim of this work was to test the concept of applying PPI glycodendrimers as drug delivery devices in order to facilitate the delivery of activated cytarabine to cancer cells to overcome metabolic limitations of the drug. The study has been carried out using 1301 and HL-60 leukemic cell lines as well as peripheral blood mononuclear cells. The results of cytotoxicity and apoptosis assays showed enhanced activity of Ara-C triphosphate form (Ara-CTP) complexed with PPI-m dendrimers in relation to free Ara-C and Ara-CTP against 1301 leukemic cells. Secondly, enhanced uptake and cytotoxicity of Ara-CTP-dendrimers complexes toward 1301 cells with blocked human equilibrative nucleoside transporter - hENT1 suggested that this combination might be a versatile candidate for chemotherapy against resistant acute lymphoblastic leukemia cells with lower expression of hENT1. Copyright © 2016 Elsevier B.V. All rights reserved.

M-52 spray booth qualification test

NASA Technical Reports Server (NTRS)

1990-01-01

The procedures, performance, and results obtained from the M-52 spray booth qualification test are documented. The test was conducted at Thiokol Corporation, Space Operations, M-52 Inert Parts Preparation facility. The purpose of this testing sequence was to ensure the spray booth would produce flight qualified hardware. The testing sequence was conducted in two series. The first series was conducted under CTP-0142, Revision 1. The second series was conducted in accordance with CTP-0142, Revision 2. The test sequence started with CTP-0142, Revision 1. The series consisted of the contamination removal test and the performance test. The contamination removal test was used to assess the Teflon level in the spray booth. The performance test consisted of painting and Chemloking a forward dome inside the spray booth per flight procedures. During the performance test, two sets of witness panels (case/insulation and steel/epoxy/steel) were prepared and pull tested. The CTP-0142, Revision 2, series of testing consisted of re-testing the steel/epoxy/steel witness panels. The pull tests analysis indicates the results of the tensile tests were comparable to the systems tunnel witness panel database. The exposed panel set and the control panel set average tensile values were above the 1-basis lower limits established on the systems tunnel witness panel database. It is recommended that the M-52 spray booth be qualified for producing flight hardware.

Quantification of the Effect of Shuttling on Computed Tomography Perfusion Parameters by Investigation of Aortic Inputs on Different Table Positions From Shuttle-Mode Scans of Lung and Liver Tumors.

PubMed

Ghosh, Payel; Chandler, Adam G; Hobbs, Brian P; Sun, Jia; Rong, John; Hong, David; Subbiah, Vivek; Janku, Filip; Naing, Aung; Hwu, Wen-Jen; Ng, Chaan S

The aim of this study was to quantify the effect of shuttling on computed tomography perfusion (CTp) parameters derived from shuttle-mode body CT images using aortic inputs from different table positions. Axial shuttle-mode CT scans were acquired from 6 patients (10 phases, 2 nonoverlapping table positions 1.4 seconds apart) after contrast agent administration. Artifacts resulting from the shuttling motion were corrected with nonrigid registration before computing CTp maps from 4 aortic levels chosen from the most superior and inferior slices of each table position scan. The effect of shuttling on CTp parameters was estimated by mean differences in mappings obtained from aortic inputs in different table positions. Shuttling effect was also quantified using 95% limits of agreement of CTp parameter differences within-table and between-table aortic positions from the interaortic mean CTp values. Blood flow, permeability surface, and hepatic arterial fraction differences were insignificant (P > 0.05) for both within-table and between-table comparisons. The 95% limits of agreement for within-table blood volume (BV) value deviations obtained from lung tumor regions were less than 4.7% (P = 0.18) compared with less than 12.2% (P = 0.003) for between-table BV value deviations. The 95% limits of agreement of within-table deviations for liver tumor regions were less than 1.9% (P = 0.55) for BV and less than 3.2% (P = 0.23) for mean transit time, whereas between-table BV and mean transit time deviations were less than 11.7% (P < 0.01) and less than 14.6% (P < 0.01), respectively. Values for normal liver tissue regions were concordant. Computed tomography perfusion parameters acquired from aortic levels within-table positions generally yielded higher agreement than mappings obtained from aortic levels between-table positions indicating differences due to shuttling effect.

Biochemical Evaluation of the Inhibition Properties of Favipiravir and 2′-C-Methyl-Cytidine Triphosphates against Human and Mouse Norovirus RNA Polymerases

PubMed Central

Tucker, Kathryn; Lin, Xiaoyan; Kao, C. Cheng; Shaw, Ken; Tan, Hua; Symons, Julian; Behera, Ishani; Rajwanshi, Vivek K.; Dyatkina, Natalia; Wang, Guangyi; Beigelman, Leo

2015-01-01

Norovirus (NoV) is a positive-sense single-stranded RNA virus that causes acute gastroenteritis and is responsible for 200,000 deaths per year worldwide. No effective vaccine or treatment is available. Recent studies have shown that the nucleoside analogs favipiravir (T-705) and 2′-C-methyl-cytidine (2CM-C) inhibit NoV replication in vitro and in animal models, but their precise mechanism of action is unknown. We evaluated the molecular interactions between nucleoside triphosphates and NoV RNA-dependent RNA polymerase (NoVpol), the enzyme responsible for replication and transcription of NoV genomic RNA. We found that T-705 ribonucleoside triphosphate (RTP) and 2CM-C triphosphate (2CM-CTP) equally inhibited human and mouse NoVpol activities at concentrations resulting in 50% of maximum inhibition (IC50s) in the low micromolar range. 2CM-CTP inhibited the viral polymerases by competing directly with natural CTP during primer elongation, whereas T-705 RTP competed mostly with ATP and GTP at the initiation and elongation steps. Incorporation of 2CM-CTP into viral RNA blocked subsequent RNA synthesis, whereas T-705 RTP did not cause immediate chain termination of NoVpol. 2CM-CTP and T-705 RTP displayed low levels of enzyme selectivity, as they were both recognized as substrates by human mitochondrial RNA polymerase. The level of discrimination by the human enzyme was increased with a novel analog of T-705 RTP containing a 2′-C-methyl substitution. Collectively, our data suggest that 2CM-C inhibits replication of NoV by acting as a classic chain terminator, while T-705 may inhibit the virus by multiple mechanisms of action. Understanding the precise mechanism of action of anti-NoV compounds could provide a rational basis for optimizing their inhibition potencies and selectivities. PMID:26392512

Structural basis for proficient incorporation of dTTP opposite O6-methylguanine by human DNA polymerase iota.

PubMed

Pence, Matthew G; Choi, Jeong-Yun; Egli, Martin; Guengerich, F Peter

2010-12-24

O(6)-methylguanine (O(6)-methylG) is highly mutagenic and is commonly found in DNA exposed to methylating agents, even physiological ones (e.g. S-adenosylmethionine). The efficiency of a truncated, catalytic DNA polymerase ι core enzyme was determined for nucleoside triphosphate incorporation opposite O(6)-methylG, using steady-state kinetic analyses. The results presented here corroborate previous work from this laboratory using full-length pol ι, which showed that dTTP incorporation occurs with high efficiency opposite O(6)-methylG. Misincorporation of dTTP opposite O(6)-methylG occurred with ∼6-fold higher efficiency than incorporation of dCTP. Crystal structures of the truncated form of pol ι with O(6)-methylG as the template base and incoming dCTP or dTTP were solved and showed that O(6)-methylG is rotated into the syn conformation in the pol ι active site and that dTTP misincorporation by pol ι is the result of Hoogsteen base pairing with the adduct. Both dCTP and dTTP base paired with the Hoogsteen edge of O(6)-methylG. A single, short hydrogen bond formed between the N3 atom of dTTP and the N7 atom of O(6)-methylG. Protonation of the N3 atom of dCTP and bifurcation of the N3 hydrogen between the N7 and O(6) atoms of O(6)-methylG allow base pairing of the lesion with dCTP. We conclude that differences in the Hoogsteen hydrogen bonding between nucleotides is the main factor in the preferential selectivity of dTTP opposite O(6)-methylG by human pol ι, in contrast to the mispairing modes observed previously for O(6)-methylG in the structures of the model DNA polymerases Sulfolobus solfataricus Dpo4 and Bacillus stearothermophilus DNA polymerase I.

Stability of radiomic features in CT perfusion maps

NASA Astrophysics Data System (ADS)

Bogowicz, M.; Riesterer, O.; Bundschuh, R. A.; Veit-Haibach, P.; Hüllner, M.; Studer, G.; Stieb, S.; Glatz, S.; Pruschy, M.; Guckenberger, M.; Tanadini-Lang, S.

2016-12-01

This study aimed to identify a set of stable radiomic parameters in CT perfusion (CTP) maps with respect to CTP calculation factors and image discretization, as an input for future prognostic models for local tumor response to chemo-radiotherapy. Pre-treatment CTP images of eleven patients with oropharyngeal carcinoma and eleven patients with non-small cell lung cancer (NSCLC) were analyzed. 315 radiomic parameters were studied per perfusion map (blood volume, blood flow and mean transit time). Radiomics robustness was investigated regarding the potentially standardizable (image discretization method, Hounsfield unit (HU) threshold, voxel size and temporal resolution) and non-standardizable (artery contouring and noise threshold) perfusion calculation factors using the intraclass correlation (ICC). To gain added value for our model radiomic parameters correlated with tumor volume, a well-known predictive factor for local tumor response to chemo-radiotherapy, were excluded from the analysis. The remaining stable radiomic parameters were grouped according to inter-parameter Spearman correlations and for each group the parameter with the highest ICC was included in the final set. The acceptance level was 0.9 and 0.7 for the ICC and correlation, respectively. The image discretization method using fixed number of bins or fixed intervals gave a similar number of stable radiomic parameters (around 40%). The potentially standardizable factors introduced more variability into radiomic parameters than the non-standardizable ones with 56-98% and 43-58% instability rates, respectively. The highest variability was observed for voxel size (instability rate  >97% for both patient cohorts). Without standardization of CTP calculation factors none of the studied radiomic parameters were stable. After standardization with respect to non-standardizable factors ten radiomic parameters were stable for both patient cohorts after correction for inter-parameter correlations. Voxel size, image discretization, HU threshold and temporal resolution have to be standardized to build a reliable predictive model based on CTP radiomics analysis.

A web-based institutional DICOM distribution system with the integration of the Clinical Trial Processor (CTP).

PubMed

Aryanto, K Y E; Broekema, A; Langenhuysen, R G A; Oudkerk, M; van Ooijen, P M A

2015-05-01

To develop and test a fast and easy rule-based web-environment with optional de-identification of imaging data to facilitate data distribution within a hospital environment. A web interface was built using Hypertext Preprocessor (PHP), an open source scripting language for web development, and Java with SQL Server to handle the database. The system allows for the selection of patient data and for de-identifying these when necessary. Using the services provided by the RSNA Clinical Trial Processor (CTP), the selected images were pushed to the appropriate services using a protocol based on the module created for the associated task. Five pipelines, each performing a different task, were set up in the server. In a 75 month period, more than 2,000,000 images are transferred and de-identified in a proper manner while 20,000,000 images are moved from one node to another without de-identification. While maintaining a high level of security and stability, the proposed system is easy to setup, it integrate well with our clinical and research practice and it provides a fast and accurate vendor-neutral process of transferring, de-identifying, and storing DICOM images. Its ability to run different de-identification processes in parallel pipelines is a major advantage in both clinical and research setting.

Thiophenecarboxamide Derivatives Activated by EthA Kill Mycobacterium tuberculosis by Inhibiting the CTP Synthetase PyrG

PubMed Central

Mori, Giorgia; Chiarelli, Laurent R.; Esposito, Marta; Makarov, Vadim; Bellinzoni, Marco; Hartkoorn, Ruben C.; Degiacomi, Giulia; Boldrin, Francesca; Ekins, Sean; de Jesus Lopes Ribeiro, Ana Luisa; Marino, Leonardo B.; Centárová, Ivana; Svetlíková, Zuzana; Blaško, Jaroslav; Kazakova, Elena; Lepioshkin, Alexander; Barilone, Nathalie; Zanoni, Giuseppe; Porta, Alessio; Fondi, Marco; Fani, Renato; Baulard, Alain R.; Mikušová, Katarína; Alzari, Pedro M.; Manganelli, Riccardo; de Carvalho, Luiz Pedro S.; Riccardi, Giovanna; Cole, Stewart T.; Pasca, Maria Rosalia

2015-01-01

Summary To combat the emergence of drug-resistant strains of Mycobacterium tuberculosis, new antitubercular agents and novel drug targets are needed. Phenotypic screening of a library of 594 hit compounds uncovered two leads that were active against M. tuberculosis in its replicating, non-replicating, and intracellular states: compounds 7947882 (5-methyl-N-(4-nitrophenyl)thiophene-2-carboxamide) and 7904688 (3-phenyl-N-[(4-piperidin-1-ylphenyl)carbamothioyl]propanamide). Mutants resistant to both compounds harbored mutations in ethA (rv3854c), the gene encoding the monooxygenase EthA, and/or in pyrG (rv1699) coding for the CTP synthetase, PyrG. Biochemical investigations demonstrated that EthA is responsible for the activation of the compounds, and by mass spectrometry we identified the active metabolite of 7947882, which directly inhibits PyrG activity. Metabolomic studies revealed that pharmacological inhibition of PyrG strongly perturbs DNA and RNA biosynthesis, and other metabolic processes requiring nucleotides. Finally, the crystal structure of PyrG was solved, paving the way for rational drug design with this newly validated drug target. PMID:26097035

How the CCA-Adding Enzyme Selects Adenine over Cytosine at Position 76 of tRNA

DOE Office of Scientific and Technical Information (OSTI.GOV)

B Pan; Y Xiong; T Steitz

2011-12-31

CCA-adding enzymes [ATP(CTP):tRNA nucleotidyltransferases] add CCA onto the 3' end of transfer RNA (tRNA) precursors without using a nucleic acid template. Although the mechanism by which cytosine (C) is selected at position 75 of tRNA has been established, the mechanism by which adenine (A) is selected at position 76 remains elusive. Here, we report five cocrystal structures of the enzyme complexed with both a tRNA mimic and nucleoside triphosphates under catalytically active conditions. These structures suggest that adenosine 5'-monophosphate is incorporated onto the A76 position of the tRNA via a carboxylate-assisted, one-metal-ion mechanism with aspartate 110 functioning as a generalmore » base. The discrimination against incorporation of cytidine 5'-triphosphate (CTP) at position 76 arises from improper placement of the {alpha} phosphate of the incoming CTP, which results from the interaction of C with arginine 224 and prevents the nucleophilic attack by the 3' hydroxyl group of cytidine75.« less

Chiral Tricritical Point: A New Universality Class in Dirac Systems

NASA Astrophysics Data System (ADS)

Yin, Shuai; Jian, Shao-Kai; Yao, Hong

2018-05-01

Tricriticality, as a sister of criticality, is a fundamental and absorbing issue in condensed-matter physics. It has been verified that the bosonic Wilson-Fisher universality class can be changed by gapless fermionic modes at criticality. However, the counterpart phenomena at tricriticality have rarely been explored. In this Letter, we study a model in which a tricritical Ising model is coupled to massless Dirac fermions. We find that the massless Dirac fermions result in the emergence of a new tricritical point, which we refer to as the chiral tricritical point (CTP), at the phase boundary between the Dirac semimetal and the charge-density wave insulator. From functional renormalization group analysis of the effective action, we obtain the critical behaviors of the CTP, which are qualitatively distinct from both the tricritical Ising universality and the chiral Ising universality. We further extend the calculations of the chiral tricritical behaviors of Ising spins to the case of Heisenberg spins. The experimental relevance of the CTP in two-dimensional Dirac semimetals is also discussed.

Cigarette smoke disrupts the integrity of airway adherens junctions through the aberrant interaction of p120-catenin with the cytoplasmic tail of MUC1

PubMed Central

Zhang, Lili; Gallup, Marianne; Zlock, Lorna; Basbaum, Carol; Finkbeiner, Walter E.; McNamara, Nancy A.

2014-01-01

Adherens junctions (AJs) containing epithelial cadherin (E-cad) bound to p120-catenin (p120ctn) and β-catenin (β-ctn) play a crucial role in regulating cell–cell adhesion. Cigarette smoke abrogates cell–cell adhesion between epithelial cells by disrupting E-cad, a hallmark of epithelial–mesenchymal transition (EMT), yet the underlying mechanism remains unknown. We used an organotypic culture of primary human bronchial epithelial (HBE) cells treated with smoke-concentrated medium (Smk) to establish an essential role for the interaction between p120ctn and the cytoplasmic tail of MUC1 (MUC1-CT) in regulating E-cad disruption. Within the first 4 h of smoke exposure, apical MUC1-CT repositioned to the basolateral membrane of pseudo-stratified HBE cells, where it interacted with p120ctn. A time-dependent increase in MUC1-CT/p120ctn complexes occurred in conjunction with a time-dependent dissociation of p120ctn/E-cad/β-ctn complexes, as well as the coordinated degradation of p120ctn and E-cad. Interestingly, Smk induced a similar interaction between MUC1-CT and β-ctn, but this occurred 44 h after MUC1-CT’s initial interaction with p120ctn, and well after the AJs were destroyed. Blocking MUC1-CT’s interaction with p120ctn using a MUC1-CT dominant-negative peptide, PMIP, successfully abolished Smk’s disruptive effects on AJs and recovered apical-basolateral polarity of HBE cells. The MUC1-CT/p120ctn interaction was highly dependent on EGFR/Src/Jnk-mediated tyrosine phosphorylation (TyrP) of MUC1-CT. Accordingly, EGFR, Src or Jnk inhibitors (AG1478, PP2, SP600125, respectively) abrogated Smk-induced MUC1-CT-TyrP, MUC1-CT/p120ctn interaction, AJ disruption, and loss of cellular polarity. Our work identified MUC1-CT and p120ctn as important regulators of epithelial polarity and cell-cell adhesion during a smoke-induced EMT-like process. Novel therapeutics designed to inhibit MUC1-CT/p120ctn complex formation may prevent EMT in the smoker’s airway. PMID:22833523

Geographic and demographic variabilities of quantitative parameters in stress myocardial computed tomography perfusion.

PubMed

Park, Jinoh; Kim, Hyun-Sook; Hwang, Hye Jeon; Yang, Dong Hyun; Koo, Hyun Jung; Kang, Joon-Won; Kim, Young-Hak

2017-09-01

To evaluate the geographic and demographic variabilities of the quantitative parameters of computed tomography perfusion (CTP) of the left ventricular (LV) myocardium in patients with normal coronary artery on computed tomography angiography (CTA). From a multicenter CTP registry of stress and static computed tomography, we retrospectively recruited 113 patients (mean age, 60 years; 57 men) without perfusion defect on visual assessment and minimal (< 20% of diameter stenosis) or no coronary artery disease on CTA. Using semiautomatic analysis software, quantitative parameters of the LV myocardium, including the myocardial attenuation in stress and rest phases, transmural perfusion ratio (TPR), and myocardial perfusion reserve index (MPRI), were evaluated in 16 myocardial segments. In the lateral wall of the LV myocardium, all quantitative parameters except for MPRI were significantly higher compared with those in the other walls. The MPRI showed consistent values in all myocardial walls (anterior to lateral wall: range, 25% to 27%; p = 0.401). At the basal level of the myocardium, all quantitative parameters were significantly lower than those at the mid- and apical levels. Compared with men, women had significantly higher values of myocardial attenuation and TPR. Age, body mass index, and Framingham risk score were significantly associated with the difference in myocardial attenuation. Geographic and demographic variabilities of quantitative parameters in stress myocardial CTP exist in healthy subjects without significant coronary artery disease. This information may be helpful when assessing myocardial perfusion defects in CTP.

Collaborative trial validation studies of real-time PCR-based GMO screening methods for detection of the bar gene and the ctp2-cp4epsps construct.

PubMed

Grohmann, Lutz; Brünen-Nieweler, Claudia; Nemeth, Anne; Waiblinger, Hans-Ulrich

2009-10-14

Polymerase Chain Reaction (PCR)-based screening methods targeting genetic elements commonly used in genetically modified (GM) plants are important tools for the detection of GM materials in food, feed, and seed samples. To expand and harmonize the screening capability of enforcement laboratories, the German Federal Office of Consumer Protection and Food Safety conducted collaborative trials for interlaboratory validation of real-time PCR methods for detection of the phosphinothricin acetyltransferase (bar) gene from Streptomyces hygroscopicus and a construct containing the 5-enolpyruvylshikimate-3-phosphate synthase gene from Agrobacterium tumefaciens sp. strain CP4 (ctp2-cp4epsps), respectively. To assess the limit of detection, precision, and accuracy of the methods, laboratories had to analyze two sets of 18 coded genomic DNA samples of events LLRice62 and MS8 with the bar method and NK603 and GT73 with the ctp2-cp4epsps method at analyte levels of 0, 0.02, and 0.1% GM content, respectively. In addition, standard DNAs were provided to the laboratories to generate calibration curves for copy number quantification of the bar and ctp2-cp4epsps target sequences present in the test samples. The study design and the results obtained are discussed with respect to the difficult issue of developing general guidelines and concepts for the collaborative trial validation of qualitative PCR screening methods.

Dipyridamole stress myocardial perfusion by computed tomography in patients with left bundle branch block.

PubMed

Cabeda, Estêvan Vieira; Falcão, Andréa Maria Gomes; Soares, José; Rochitte, Carlos Eduardo; Nomura, César Higa; Ávila, Luiz Francisco Rodrigues; Parga, José Rodrigues

2015-12-01

Functional tests have limited accuracy for identifying myocardial ischemia in patients with left bundle branch block (LBBB). To assess the diagnostic accuracy of dipyridamole-stress myocardial computed tomography perfusion (CTP) by 320-detector CT in patients with LBBB using invasive quantitative coronary angiography (QCA) (stenosis ≥ 70%) as reference; to investigate the advantage of adding CTP to coronary computed tomography angiography (CTA) and compare the results with those of single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy. Thirty patients with LBBB who had undergone SPECT for the investigation of coronary artery disease were referred for stress tomography. Independent examiners performed per-patient and per-coronary territory assessments. All patients gave written informed consent to participate in the study that was approved by the institution's ethics committee. The patients' mean age was 62 ± 10 years. The mean dose of radiation for the tomography protocol was 9.3 ± 4.6 mSv. With regard to CTP, the per-patient values for sensitivity, specificity, positive and negative predictive values, and accuracy were 86%, 81%, 80%, 87%, and 83%, respectively (p = 0.001). The per-territory values were 63%, 86%, 65%, 84%, and 79%, respectively (p < 0.001). In both analyses, the addition of CTP to CTA achieved higher diagnostic accuracy for detecting myocardial ischemia than SPECT (p < 0.001). The use of the stress tomography protocol is feasible and has good diagnostic accuracy for assessing myocardial ischemia in patients with LBBB.

Variation in primary and culture-expanded cells derived from connective tissue progenitors in human bone marrow space, bone trabecular surface and adipose tissue.

PubMed

Qadan, Maha A; Piuzzi, Nicolas S; Boehm, Cynthia; Bova, Wesley; Moos, Malcolm; Midura, Ronald J; Hascall, Vincent C; Malcuit, Christopher; Muschler, George F

2018-03-01

Connective tissue progenitors (CTPs) embody the heterogeneous stem and progenitor cell populations present in native tissue. CTPs are essential to the formation and remodeling of connective tissue and represent key targets for tissue-engineering and cell-based therapies. To better understand and characterize CTPs, we aimed to compare the (i) concentration and prevalence, (ii) early in vitro biological behavior and (iii) expression of surface-markers and transcription factors among cells derived from marrow space (MS), trabecular surface (TS), and adipose tissues (AT). Cancellous-bone and subcutaneous-adipose tissues were collected from 8 patients. Cells were isolated and cultured. Colony formation was assayed using Colonyze software based on ASTM standards. Cell concentration ([Cell]), CTP concentration ([CTP]) and CTP prevalence (P CTP ) were determined. Attributes of culture-expanded cells were compared based on (i) effective proliferation rate and (ii) expression of surface-markers CD73, CD90, CD105, SSEA-4, SSEA-3, SSEA-1/CD15, Cripto-1, E-Cadherin/CD324, Ep-CAM/CD326, CD146, hyaluronan and transcription factors Oct3/4, Sox-2 and Nanog using flow cytometry. Mean [Cell], [CTP] and P CTP were significantly different between MS and TS samples (P = 0.03, P = 0.008 and P= 0.0003), respectively. AT-derived cells generated the highest mean total cell yield at day 6 of culture-4-fold greater than TS and more than 40-fold greater than MS per million cells plated. TS colonies grew with higher mean density than MS colonies (290 ± 11 versus 150 ± 11 cell per mm 2 ; P = 0.0002). Expression of classical-mesenchymal stromal cell (MSC) markers was consistently recorded (>95%) from all tissue sources, whereas all the other markers were highly variable. The prevalence and biological potential of CTPs are different between patients and tissue sources and lack variation in classical MSC markers. Other markers are more likely to discriminate differences between cell populations in biological performance. Understanding the underlying reasons for variation in the concentration, prevalence, marker expression and biological potential of CTPs between patients and source tissues and determining the means of managing this variation will contribute to the rational development of cell-based clinical diagnostics and targeted cell-based therapies. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Production data in media systems and press front ends: capture, formats and database methods

NASA Astrophysics Data System (ADS)

Karttunen, Simo

1997-02-01

The nature, purpose and data presentation features of media jobs are analyzed in relation to the content, document, process and resource management in media production. Formats are the natural way of presenting, collecting and storing information, contents, document components and final documents. The state of the art and the trends in the media formats and production data are reviewed. The types and the amount of production data are listed, e.g. events, schedules, product descriptions, reports, visual support, quality, process states and color data. The data exchange must be vendor-neutral. Adequate infrastructure and system architecture are defined for production and media data. The roles of open servers and intranets are evaluated and their potential roles as future solutions are anticipated. The press frontend is the part of print media production where large files dominate. The new output alternatives, i.e. film recorders, direct plate output (CTP and CTP-on-press) and digital, plateless printing lines need new workflow tools and very efficient file and format management. The paper analyzes the capture, formatting and storing of job files and respective production data, such as the event logs of the processes. Intranet, browsers, Java applets and open web severs will be used to capture production data, especially where intranets are used anyhow, or where several companies are networked to plan, design and use documents and printed products. The user aspects of installing intranets is stressed since there are numerous more traditional and more dedicated networking solutions on the market.

Calculation of electromagnetic force in electromagnetic forming process of metal sheet

NASA Astrophysics Data System (ADS)

Xu, Da; Liu, Xuesong; Fang, Kun; Fang, Hongyuan

2010-06-01

Electromagnetic forming (EMF) is a forming process that relies on the inductive electromagnetic force to deform metallic workpiece at high speed. Calculation of the electromagnetic force is essential to understand the EMF process. However, accurate calculation requires complex numerical solution, in which the coupling between the electromagnetic process and the deformation of workpiece needs be considered. In this paper, an appropriate formula has been developed to calculate the electromagnetic force in metal work-piece in the sheet EMF process. The effects of the geometric size of coil, the material properties, and the parameters of discharge circuit on electromagnetic force are taken into consideration. Through the formula, the electromagnetic force at different time and in different positions of the workpiece can be predicted. The calculated electromagnetic force and magnetic field are in good agreement with the numerical and experimental results. The accurate prediction of the electromagnetic force provides an insight into the physical process of the EMF and a powerful tool to design optimum EMF systems.

Effects of transcriptional start site sequence and position on nucleotide-sensitive selection of alternative start sites at the pyrC promoter in Escherichia coli.

PubMed Central

Liu, J; Turnbough, C L

1994-01-01

In Escherichia coli, expression of the pyrC gene is regulated primarily by a translational control mechanism based on nucleotide-sensitive selection of transcriptional start sites at the pyrC promoter. When intracellular levels of CTP are high, pyrC transcripts are initiated predominantly with CTP at a site 7 bases downstream of the Pribnow box. These transcripts form a stable hairpin at their 5' ends that blocks ribosome binding. When the CTP level is low and the GTP level is high, conditions found in pyrimidine-limited cells, transcripts are initiated primarily with GTP at a site 9 bases downstream of the Pribnow box. These shorter transcripts are unable to form a hairpin at their 5' ends and are readily translated. In this study, we examined the effects of nucleotide sequence and position on the selection of transcriptional start sites at the pyrC promoter. We characterized promoter mutations that systematically alter the sequence at position 7 or 9 downstream of the Pribnow box or vary the spacing between the Pribnow box and wild-type transcriptional initiation region. The results reveal preferences for particular initiating nucleotides (ATP > or = GTP > UTP >> CTP) and for starting positions downstream of the Pribnow box (7 >> 6 and 8 > 9 > 10). The results indicate that optimal nucleotide-sensitive start site switching at the wild-type pyrC promoter is the result of competition between the preferred start site (position 7) that uses the poorest initiating nucleotide (CTP) and a weak start site (position 9) that uses a good initiating nucleotide (GTP). The sequence of the pyrC promoter also minimizes the synthesis of untranslatable transcripts and provides for maximum stability of the regulatory transcript hairpin. In addition, the results show that the effects of the mutations on pyrC expression and regulation are consistent with the current model for translational control. Possible effects of preferences for initiating nucleotides and start sites on the expression and regulation of other genes are discussed. Images PMID:7910603

Farnesol is utilized for isoprenoid biosynthesis in plant cells via farnesyl pyrophosphate formed by successive monophosphorylation reactions

PubMed Central

Thai, Long; Rush, Jeffrey S.; Maul, Jude E.; Devarenne, Timothy; Rodgers, Dana L.; Chappell, Joseph; Waechter, Charles J.

1999-01-01

The ability of Nicotiana tabacum cell cultures to utilize farnesol (F-OH) for sterol and sesquiterpene biosynthesis was investigated. [3H]F-OH was readily incorporated into sterols by rapidly growing cell cultures. However, the incorporation rate into sterols was reduced by greater than 70% in elicitor-treated cell cultures whereas a substantial proportion of the radioactivity was redirected into capsidiol, an extracellular sesquiterpene phytoalexin. The incorporation of [3H]F-OH into sterols was inhibited by squalestatin 1, suggesting that [3H]F-OH was incorporated via farnesyl pyrophosphate (F-P-P). Consistent with this possibility, N. tabacum proteins were metabolically labeled with [3H]F-OH or [3H]geranylgeraniol ([3H]GG-OH). Kinase activities converting F-OH to farnesyl monophosphate (F-P) and, subsequently, F-P-P were demonstrated directly by in vitro enzymatic studies. [3H]F-P and [3H]F-P-P were synthesized when exogenous [3H]F-OH was incubated with microsomal fractions and CTP. The kinetics of formation suggested a precursor–product relationship between [3H]F-P and [3H]F-P-P. In agreement with this kinetic pattern of labeling, [32P]F-P and [32P]F-P-P were synthesized when microsomal fractions were incubated with F-OH and F-P, respectively, with [γ-32P]CTP serving as the phosphoryl donor. Under similar conditions, the microsomal fractions catalyzed the enzymatic conversion of [3H]GG-OH to [3H]geranylgeranyl monophosphate and [3H]geranylgeranyl pyrophosphate ([3H]GG-P-P) in CTP-dependent reactions. A novel biosynthetic mechanism involving two successive monophosphorylation reactions was supported by the observation that [3H]CTP was formed when microsomes were incubated with [3H]CDP and either F-P-P or GG-P-P, but not F-P. These results document the presence of at least two CTP-mediated kinases that provide a mechanism for the utilization of F-OH and GG-OH for the biosynthesis of isoprenoid lipids and protein isoprenylation. PMID:10557276

Absolute Cerebral Blood Flow Infarction Threshold for 3-Hour Ischemia Time Determined with CT Perfusion and 18F-FFMZ-PET Imaging in a Porcine Model of Cerebral Ischemia

PubMed Central

Cockburn, Neil; Kovacs, Michael

2016-01-01

CT Perfusion (CTP) derived cerebral blood flow (CBF) thresholds have been proposed as the optimal parameter for distinguishing the infarct core prior to reperfusion. Previous threshold-derivation studies have been limited by uncertainties introduced by infarct expansion between the acute phase of stroke and follow-up imaging, or DWI lesion reversibility. In this study a model is proposed for determining infarction CBF thresholds at 3hr ischemia time by comparing contemporaneously acquired CTP derived CBF maps to 18F-FFMZ-PET imaging, with the objective of deriving a CBF threshold for infarction after 3 hours of ischemia. Endothelin-1 (ET-1) was injected into the brain of Duroc-Cross pigs (n = 11) through a burr hole in the skull. CTP images were acquired 10 and 30 minutes post ET-1 injection and then every 30 minutes for 150 minutes. 370 MBq of 18F-FFMZ was injected ~120 minutes post ET-1 injection and PET images were acquired for 25 minutes starting ~155–180 minutes post ET-1 injection. CBF maps from each CTP acquisition were co-registered and converted into a median CBF map. The median CBF map was co-registered to blood volume maps for vessel exclusion, an average CT image for grey/white matter segmentation, and 18F-FFMZ-PET images for infarct delineation. Logistic regression and ROC analysis were performed on infarcted and non-infarcted pixel CBF values for each animal that developed infarct. Six of the eleven animals developed infarction. The mean CBF value corresponding to the optimal operating point of the ROC curves for the 6 animals was 12.6 ± 2.8 mL·min-1·100g-1 for infarction after 3 hours of ischemia. The porcine ET-1 model of cerebral ischemia is easier to implement then other large animal models of stroke, and performs similarly as long as CBF is monitored using CTP to prevent reperfusion. PMID:27347877

Progenitor cells from different zones of human cartilage and their correlation with histopathological osteoarthritis progression.

PubMed

Mantripragada, Venkata P; Bova, Wesley A; Boehm, Cynthia; Piuzzi, Nicolas S; Obuchowski, Nancy A; Midura, Ronald J; Muschler, George F

2018-06-01

Cell-based therapies development for the treatment of osteoarthritis (OA) requires an understanding of the disease progression and attributes of the cells resident in cartilage. This study focused on quantitative assessment of the concentration and biological potential of stem and progenitor cells resident in different zones of cartilage displaying macroscopic Outerbridge grade 1-2 OA, and their correlation with OA progression based on established histologic scoring system. Lateral femoral condyles were collected from 15 patients with idiopathic OA and varus knees undergoing total knee arthroplasty. Superficial(C sp , top ∼ 500 µm) and deep cartilage(C dp ) was separated. Chondrogenic Connective Tissue Progenitors (CTP-C) were assayed by standardized Colony-Forming-Unit assay using automated image analysis (Colonyze TM ) based on ASTM standard F-2944-12. Cell concentration (cells/mg) was significantly greater in C sp (median: 7,000; range: 3,440-17,600) than C dp (median: 5,340; range: 3,393-9,660), p = 0.039. Prevalence (CTPs/million cells) was not different between C sp (median: 1,274; range: 0-3,898) and C dp (median:1,365; range:0-6,330), p = 0.42. In vitro performance of CTP-C progeny varied widely within and between patients, manifest by variation in colony size and morphology. Mean histopathological Mankin score was 4.7 (SD = 1.2), representing mild to moderate OA. Tidemark breach by blood vessels was associated with lower C sp cell concentration (p = 0.02). Matrix degradation was associated with lower C dp cell and CTP-C concentration (p = 0.015 and p = 0.095, respectively), independent of articular surface changes. These findings suggest that the initiation of OA may occur in either superficial or deep zones. The pathological changes affect CTP-Cs in C sp and C dp cartilage zones differently. The heterogeneity among the available CTP-Cs in C sp and C dp suggests performance-based selection to optimize cell-sourcing strategies for therapy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1728-1738, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Structural Basis for Proficient Incorporation of dTTP Opposite O[superscript 6]-Methylguanine by Human DNA Polymerase [iota

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pence, Matthew G.; Choi, Jeong-Yun; Egli, Martin

2012-03-15

O{sup 6}-Methylguanine (O{sup 6}-methylG) is highly mutagenic and is commonly found in DNA exposed to methylating agents, even physiological ones (e.g. S-adenosylmethionine). The efficiency of a truncated, catalytic DNA polymerase L core enzyme was determined for nucleoside triphosphate incorporation opposite O{sup 6}-methylG, using steady-state kinetic analyses. The results presented here corroborate previous work from this laboratory using full-length pol L, which showed that dTTP incorporation occurs with high efficiency opposite O{sup 6}-methylG. Misincorporation of dTTP opposite O{sup 6}-methylG occurred with {approx}6-fold higher efficiency than incorporation of dCTP. Crystal structures of the truncated form of pol L with O{sup 6}-methylG asmore » the template base and incoming dCTP or dTTP were solved and showed that O{sup 6}-methylG is rotated into the syn conformation in the pol L active site and that dTTP misincorporation by pol L is the result of Hoogsteen base pairing with the adduct. Both dCTP and dTTP base paired with the Hoogsteen edge of O{sup 6}-methylG. A single, short hydrogen bond formed between the N3 atom of dTTP and the N7 atom of O{sup 6}-methylG. Protonation of the N3 atom of dCTP and bifurcation of the N3 hydrogen between the N7 and O{sup 6} atoms of O{sup 6}-methylG allow base pairing of the lesion with dCTP. We conclude that differences in the Hoogsteen hydrogen bonding between nucleotides is the main factor in the preferential selectivity of dTTP opposite O{sup 6}-methylG by human pol L, in contrast to the mispairing modes observed previously for O{sup 6}-methylG in the structures of the model DNA polymerases Sulfolobus solfataricus Dpo4 and Bacillus stearothermophilus DNA polymerase I.« less

Associations Between Serum Bone Biomarkers in Early Breast Cancer and Development of Bone Metastasis: Results From the AZURE (BIG01/04) Trial.

PubMed

Brown, Janet; Rathbone, Emma; Hinsley, Samantha; Gregory, Walter; Gossiel, Fatma; Marshall, Helen; Burkinshaw, Roger; Shulver, Helen; Thandar, Hasina; Bertelli, Gianfilippo; Maccon, Keane; Bowman, Angela; Hanby, Andrew; Bell, Richard; Cameron, David; Coleman, Robert

2018-02-07

Adjuvant therapies can prevent/delay bone metastasis development in breast cancer. We investigated whether serum bone turnover markers in early disease have clinical utility in identifying patients with a high risk of developing bone metastasis. Markers of bone formation (N-terminal propeptide of type-1 collagen [P1NP]) and bone resorption (C-telopeptide of type-1 collagen [CTX], pyridinoline cross-linked carboxy-terminal telopeptide of type-1 collagen [1-CTP]) were measured in baseline (pretreatment blood samples from 872 patients from a large randomized trial of adjuvant zoledronic acid (AZURE-ISRCTN79831382) in early breast cancer. Cox proportional hazards regression and cumulative incidence functions (adjusted for factors having a statistically significant effect on outcome) were used to investigate prognostic and predictive associations between recurrence events, bone marker levels, and clinical variables. All statistical tests were two-sided. When considered as continuous variables (log transformed), P1NP, CTX, and 1-CTP were each prognostic for future bone recurrence at any time (P = .006, P = .009, P = .008, respectively). Harrell's c-indices were a P1NP of 0.57 (95% confidence interval [CI] = 0.51 to 0.63), CTX of 0.57 (95% CI = 0.51 to 0.62), and 1-CTP of 0.57 (95% CI = 0.52 to 0.63). In categorical analyses based on the normal range, high baseline P1NP (>70 ng/mL) and CTX (>0.299 ng/mL), but not 1-CTP (>4.2 ng/mL), were also prognostic for future bone recurrence (P = .03, P = .03, P = .10, respectively). None of the markers were prognostic for overall distant recurrence; that is, they were bone metastasis specific, and none of the markers were predictive of treatment benefit from zoledronic acid. Serum P1NP, CTX, and 1-CTP are clinically useful, easily measured markers that show good prognostic ability (though low-to-moderate discrimination) for bone-specific recurrence and are worthy of further study. © The Author(s) 2018. Published by Oxford University Press.

Farnesol is utilized for isoprenoid biosynthesis in plant cells via farnesyl pyrophosphate formed by successive monophosphorylation reactions.

PubMed

Thai, L; Rush, J S; Maul, J E; Devarenne, T; Rodgers, D L; Chappell, J; Waechter, C J

1999-11-09

The ability of Nicotiana tabacum cell cultures to utilize farnesol (F-OH) for sterol and sesquiterpene biosynthesis was investigated. [(3)H]F-OH was readily incorporated into sterols by rapidly growing cell cultures. However, the incorporation rate into sterols was reduced by greater than 70% in elicitor-treated cell cultures whereas a substantial proportion of the radioactivity was redirected into capsidiol, an extracellular sesquiterpene phytoalexin. The incorporation of [(3)H]F-OH into sterols was inhibited by squalestatin 1, suggesting that [(3)H]F-OH was incorporated via farnesyl pyrophosphate (F-P-P). Consistent with this possibility, N. tabacum proteins were metabolically labeled with [(3)H]F-OH or [(3)H]geranylgeraniol ([(3)H]GG-OH). Kinase activities converting F-OH to farnesyl monophosphate (F-P) and, subsequently, F-P-P were demonstrated directly by in vitro enzymatic studies. [(3)H]F-P and [(3)H]F-P-P were synthesized when exogenous [(3)H]F-OH was incubated with microsomal fractions and CTP. The kinetics of formation suggested a precursor-product relationship between [(3)H]F-P and [(3)H]F-P-P. In agreement with this kinetic pattern of labeling, [(32)P]F-P and [(32)P]F-P-P were synthesized when microsomal fractions were incubated with F-OH and F-P, respectively, with [gamma-(32)P]CTP serving as the phosphoryl donor. Under similar conditions, the microsomal fractions catalyzed the enzymatic conversion of [(3)H]GG-OH to [(3)H]geranylgeranyl monophosphate and [(3)H]geranylgeranyl pyrophosphate ([(3)H]GG-P-P) in CTP-dependent reactions. A novel biosynthetic mechanism involving two successive monophosphorylation reactions was supported by the observation that [(3)H]CTP was formed when microsomes were incubated with [(3)H]CDP and either F-P-P or GG-P-P, but not F-P. These results document the presence of at least two CTP-mediated kinases that provide a mechanism for the utilization of F-OH and GG-OH for the biosynthesis of isoprenoid lipids and protein isoprenylation.

The effect of sprinting after each set of heavy resistance training on the running speed and jumping performance of young basketball players.

PubMed

Tsimahidis, Konstantinos; Galazoulas, Christos; Skoufas, Dimitrios; Papaiakovou, Georgios; Bassa, Eleni; Patikas, Dimitrios; Kotzamanidis, Christos

2010-08-01

The purpose of this study was to investigate the effect of a 10-week heavy resistance combined with a running training program on the strength, running speed (RS), and vertical jump performance of young basketball players. Twenty-six junior basketball players were equally divided in 2 groups. The control (CON) group performed only technical preparation and the group that followed the combined training program (CTP) performed additionally 5 sets of 8-5 repetition maximum (RM) half squat with 1 30-m sprint after each set. The evaluation took place before training and after the 5th and 10th weeks of training. Apart from the 1RM half squat test, the 10- and 30-m running time was measured using photocells and the jump height (squat, countermovement jump, and drop jump) was estimated taking into account the flight time. The 1RM increased by 30.3 +/- 1.5% at the 10th week of training for the CTP group (p < 0.05), whereas the CON group showed no significant increase (1.1 +/- 1.6%, p > 0.05). In general, all measured parameters showed a statistically significant increase after the 5th and 10th weeks (p < 0.05), in contrast to the CON group (p > 0.05). This suggests that the applied CTP is beneficial for the strength, RS, and jump height of young basketball players. The observed adaptations in the CTP group could be attributed to learning factors and to a more optimal transfer of the strength gain to running and jumping performance.

The spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β

PubMed Central

Koag, Myong-Chul; Nam, Kwangho; Lee, Seongmin

2014-01-01

To provide molecular-level insights into the spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β (polβ), we report four crystal structures of polβ complexed with dG•dTTP and dA•dCTP mismatches in the presence of Mg2+ or Mn2+. The Mg2+-bound ground-state structures show that the dA•dCTP-Mg2+ complex adopts an ‘intermediate’ protein conformation while the dG•dTTP-Mg2+ complex adopts an open protein conformation. The Mn2+-bound ‘pre-chemistry-state’ structures show that the dA•dCTP-Mn2+ complex is structurally very similar to the dA•dCTP-Mg2+ complex, whereas the dG•dTTP-Mn2+ complex undergoes a large-scale conformational change to adopt a Watson–Crick-like dG•dTTP base pair and a closed protein conformation. These structural differences, together with our molecular dynamics simulation studies, suggest that polβ increases replication fidelity via a two-stage mismatch discrimination mechanism, where one is in the ground state and the other in the closed conformation state. In the closed conformation state, polβ appears to allow only a Watson–Crick-like conformation for purine•pyrimidine base pairs, thereby discriminating the mismatched base pairs based on their ability to form the Watson–Crick-like conformation. Overall, the present studies provide new insights into the spontaneous replication error and the replication fidelity mechanisms of polβ. PMID:25200079

Prospective assessment of bone turnover and clinical bone diseases after allogeneic hematopoietic stem-cell transplantation.

PubMed

Petropoulou, Anna D; Porcher, Raphael; Herr, Andrée-Laure; Devergie, Agnès; Brentano, Thomas Funck; Ribaud, Patricia; Pinto, Fernando O; Rocha, Vanderson; Peffault de Latour, Régis; Orcel, Philippe; Socié, Gérard; Robin, Marie

2010-06-15

Bone complications after hematopoietic stem-cell transplantation (HSCT) are relatively frequent. Evaluation of biomarkers of bone turnover and dual energy x-ray absorptiometry (DEXA) are not known in this context. We prospectively evaluated bone mineral density, biomarkers of bone turnover, and the cumulative incidence of bone complications after allogeneic HSCT. One hundred forty-six patients were included. Bone mineral density was measured by DEXA 2-month and 1-year post-HSCT. The markers of bone turnover were serum C-telopeptide (C-TP), 5 tartrate-resistant acid phosphatase (bone resorption), and osteocalcin (bone formation) determined pre-HSCT and 2 months and 1 year thereafter. Potential association between osteoporosis at 2 months, osteoporotic fracture or avascular necrosis and, individual patient's characteristics and biologic markers were tested. C-TP was high before and 2 months after transplant. At 2 months, DEXA detected osteoporosis in more than half the patients tested. Male sex, median age less than or equal to 15 years, and abnormal C-TP before HSCT were risk factors significantly associated with osteoporosis. Three-year cumulative incidences of fractures and avascular necrosis were 8% and 11%, respectively. Children were at higher risk of fracture, whereas corticosteroid treatment duration was a significant risk factor for developing a clinical bone complication post-HSCT. Bone complications and osteoporosis are frequent after HSCT. Bone biologic markers and DEXA showed that subclinical bone abnormalities appeared early post-HSCT. The risk factors, age, gender, and C-TP easily available at the time of transplantation were identified. Biphosphonates should probably be given to patients with those risk factors.

Different CT perfusion algorithms in the detection of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

PubMed

Cremers, Charlotte H P; Dankbaar, Jan Willem; Vergouwen, Mervyn D I; Vos, Pieter C; Bennink, Edwin; Rinkel, Gabriel J E; Velthuis, Birgitta K; van der Schaaf, Irene C

2015-05-01

Tracer delay-sensitive perfusion algorithms in CT perfusion (CTP) result in an overestimation of the extent of ischemia in thromboembolic stroke. In diagnosing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH), delayed arrival of contrast due to vasospasm may also overestimate the extent of ischemia. We investigated the diagnostic accuracy of tracer delay-sensitive and tracer delay-insensitive algorithms for detecting DCI. From a prospectively collected series of aSAH patients admitted between 2007-2011, we included patients with any clinical deterioration other than rebleeding within 21 days after SAH who underwent NCCT/CTP/CTA imaging. Causes of clinical deterioration were categorized into DCI and no DCI. CTP maps were calculated with tracer delay-sensitive and tracer delay-insensitive algorithms and were visually assessed for the presence of perfusion deficits by two independent observers with different levels of experience. The diagnostic value of both algorithms was calculated for both observers. Seventy-one patients were included. For the experienced observer, the positive predictive values (PPVs) were 0.67 for the delay-sensitive and 0.66 for the delay-insensitive algorithm, and the negative predictive values (NPVs) were 0.73 and 0.74. For the less experienced observer, PPVs were 0.60 for both algorithms, and NPVs were 0.66 for the delay-sensitive and 0.63 for the delay-insensitive algorithm. Test characteristics are comparable for tracer delay-sensitive and tracer delay-insensitive algorithms for the visual assessment of CTP in diagnosing DCI. This indicates that both algorithms can be used for this purpose.

How the CCA-Adding Enzyme Selects Adenine over Cytosine at Position 76 of tRNA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pan, Baocheng; Xiong, Yong; Steitz, Thomas A.

2010-11-22

CCA-adding enzymes [ATP(CTP):tRNA nucleotidyltransferases] add CCA onto the 3{prime} end of transfer RNA (tRNA) precursors without using a nucleic acid template. Although the mechanism by which cytosine (C) is selected at position 75 of tRNA has been established, the mechanism by which adenine (A) is selected at position 76 remains elusive. Here, we report five cocrystal structures of the enzyme complexed with both a tRNA mimic and nucleoside triphosphates under catalytically active conditions. These structures suggest that adenosine 5{prime}-monophosphate is incorporated onto the A76 position of the tRNA via a carboxylate-assisted, one-metal-ion mechanism with aspartate 110 functioning as a generalmore » base. The discrimination against incorporation of cytidine 5{prime}-triphosphate (CTP) at position 76 arises from improper placement of the {alpha} phosphate of the incoming CTP, which results from the interaction of C with arginine 224 and prevents the nucleophilic attack by the 3{prime} hydroxyl group of cytidine75.« less

Computed Tomography Perfusion Imaging for the Diagnosis of Hepatic Alveolar Echinococcosis

PubMed Central

Sade, Recep; Kantarci, Mecit; Genc, Berhan; Ogul, Hayri; Gundogdu, Betul; Yilmaz, Omer

2018-01-01

Objective: Alveolar echinococcosis (AE) is a rare life-threatening parasitic infection. Computed tomography perfusion (CTP) imaging has the potential to provide both quantitative and qualitative information about the tissue perfusion characteristics. The purpose of this study was the examination of the characteristic features and feasibility of CTP in AE liver lesions. Material and Methods: CTP scanning was performed in 25 patients who had a total of 35 lesions identified as AE of the liver. Blood flow (BF), blood volume (BV), portal venous perfusion (PVP), arterial liver perfusion (ALP), and hepatic perfusion indexes (HPI) were computed for background liver parenchyma and each AE lesion. Results: Significant differences were detected between perfusion values of the AE lesions and background liver tissue. The BV, BF, ALP, and PVP values for all components of the AE liver lesions were significantly lower than the normal liver parenchyma (p<0.01). Conclusions: We suggest that perfusion imaging can be used in AE of the liver. Thus, the quantitative knowledge of perfusion parameters are obtained via CT perfusion imaging. PMID:29531482

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vyas, Rajan; Reed, Andrew J.; Tokarsky, E. John

One common oxidative DNA lesion, 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG), is highly mutagenic in vivo due to its anti-conformation forming a Watson–Crick base pair with correct deoxycytidine 5'-triphosphate (dCTP) and its syn-conformation forming a Hoogsteen base pair with incorrect deoxyadenosine 5'-triphosphate (dATP). Here in this article, we utilized time-resolved X-ray crystallography to follow 8-oxoG bypass by human DNA polymerase β (hPolβ). In the 12 solved structures, both Watson–Crick (anti-8-oxoG:anti-dCTP) and Hoogsteen (syn-8-oxoG:anti-dATP) base pairing were clearly visible and were maintained throughout the chemical reaction. Additionally, a third Mg 2+ appeared during the process of phosphodiester bond formation and was located between the reactingmore » α- and β-phosphates of the dNTP, suggesting its role in stabilizing reaction intermediates. After phosphodiester bond formation, hPolβ reopened its conformation, pyrophosphate was released, and the newly incorporated primer 3'-terminal nucleotide stacked, rather than base paired, with 8-oxoG. These structures provide the first real-time pictures, to our knowledge, of how a polymerase correctly and incorrectly bypasses a DNA lesion.« less

Regulation of Phosphatidylethanolamine Homeostasis—The Critical Role of CTP:Phosphoethanolamine Cytidylyltransferase (Pcyt2)

PubMed Central

Pavlovic, Zvezdan; Bakovic, Marica

2013-01-01

Phosphatidylethanolamine (PE) is the most abundant lipid on the protoplasmatic leaflet of cellular membranes. It has a pivotal role in cellular processes such as membrane fusion, cell cycle regulation, autophagy, and apoptosis. CTP:phosphoethanolamine cytidylyltransferase (Pcyt2) is the main regulatory enzyme in de novo biosynthesis of PE from ethanolamine and diacylglycerol by the CDP-ethanolamine Kennedy pathway. The following is a summary of the current state of knowledge on Pcyt2 and how splicing and isoform specific differences could lead to variations in functional properties in this family of enzymes. Results from the most recent studies on Pcyt2 transcriptional regulation, promoter function, autophagy, and cell growth regulation are highlighted. Recent data obtained from Pcyt2 knockout mouse models is also presented, demonstrating the essentiality of this gene in embryonic development as well as the major physiological consequences of deletion of one Pcyt2 allele. Those include development of symptoms of the metabolic syndrome such as elevated lipogenesis and lipoprotein secretion, hypertriglyceridemia, liver steatosis, obesity, and insulin resistance. The objective of this review is to elucidate the nature of Pcyt2 regulation by linking its catalytic function with the regulation of lipid and energy homeostasis. PMID:23354482

Modified CLIP with objective liver reserve assessment retains prognosis prediction for patients with advanced hepatocellular carcinoma.

PubMed

Shao, Yu-Yun; Liu, Tsung-Hao; Lee, Ying-Hui; Hsu, Chih-Hung; Cheng, Ann-Lii

2016-07-01

The Cancer of the Liver Italian Program (CLIP) score is a commonly used staging system for hepatocellular carcinoma (HCC) helpful with predicting prognosis of advanced HCC. CLIP uses the Child-Turcotte-Pugh (CTP) score to evaluate liver reserve. A new scoring system, the albumin-bilirubin (ALBI) grade, has been proposed as they objectively evaluate liver reserve. We examined whether the modification of CLIP with ALBI retained its prognosis prediction for patients with advanced HCC. We included patients who received first-line antiangiogenic therapy for advanced HCC. Liver reserve was assessed using CTP and ALBI scores, which were then incorporated into CLIP and ALBI-CLIP, respectively. To assess their efficacies of prognostic prediction, the Cox's proportional hazard model and concordance indexes were used. A total of 142 patients were included; 137 of them were classified CTP A and 5 patients CTP B. Patients could be divided into four or five groups with different prognosis according to CLIP and ALBI-CLIP, respectively. Higher R(2) (0.249 vs 0.216) and lower Akaike information criterion (995.0 vs 1001.1) were observed for ALBI-CLIP than for CLIP in the Cox's model predicting overall survival. ALBI-CLIP remained an independent predictor for overall survival when CLIP and ALBI-CLIP were simultaneously incorporated in Cox's models allowing variable selection with adjustment for hepatitis etiology, treatment, and performance status. The concordance index was also higher for ALBI-CLIP than for CLIP (0.724 vs 0.703). Modification of CLIP scoring with ALBI, which objectively assesses liver reserve, retains and might have improved prognosis prediction for advanced HCC. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Antipyrimidine effects of five different pyrimidine de novo synthesis inhibitors in three head and neck cancer cell lines.

PubMed

Peters, Godefridus J

2018-05-03

The pyrimidine de novo nucleotide synthesis consists of 6 sequential steps. Various inhibitors against these enzymes have been developed and evaluated in the clinic for their potential anticancer activity: acivicin inhibits carbamoyl-phosphate-synthase-II, N-(phosphonacetyl)-L- aspartate (PALA) inhibits aspartate-transcarbamylase, Brequinar sodium and dichloroallyl-lawsone (DCL) inhibit dihydroorotate-dehydrogenase, and pyrazofurin (PF) inhibits orotate-phosphoribosyltransferase. We compared their growth inhibition against 3 cell lines from head-and-neck-cancer (HEP-2, UMSCC-14B and UMSCC-14C) and related the sensitivity to their effects on nucleotide pools. In all cell lines Brequinar and PF were the most active compounds with IC50 (50% growth inhibition) values between 0.06-0.37 µM, Acivicin was as potent (IC50s 0.26-1 µM), but DCL was 20-31-fold less active. PALA was most inactive (24-128 µM). At equitoxic concentrations, all pure antipyrimidine de novo inhibitors depleted UTP and CTP after 24 hr exposure, which was most pronounced for Brequinar (between 6-10% of UTP left, and 12-36% CTP), followed by DCL and PF, which were almost similar (6-16% UTP and 12-27% CTP), while PALA was the least active compound (10-70% UTP and 13-68% CTP). Acivicin is a multi-target inhibitor of more glutamine requiring enzymes (including GMP synthetase) and no decrease of UTP was found, but a pronounced decrease in GTP (31-72% left). In conclusion, these 5 inhibitors of the pyrimidine de novo nucleotide synthesis varied considerably in their efficacy and effect on pyrimidine nucleotide pools. Inhibitors of DHO-DH were most effective suggesting a primary role of this enzyme in controlling pyrimidine nucleotide pools.

Myocardial perfusion 320-row multidetector computed tomography-guided treatment strategy for the clinical management of patients with recent acute-onset chest pain: Design of the CArdiac cT in the treatment of acute CHest pain (CATCH)-2 randomized controlled trial.

PubMed

Sørgaard, Mathias; Linde, Jesper J; Hove, Jens D; Petersen, Jan R; Jørgensen, Tem B S; Abdulla, Jawdat; Heitmann, Merete; Kragelund, Charlotte; Hansen, Thomas Fritz; Udholm, Patricia M; Pihl, Christian; Kühl, J Tobias; Engstrøm, Thomas; Jensen, Jan Skov; Høfsten, Dan E; Kelbæk, Henning; Kofoed, Klaus F

2016-09-01

Patients admitted with chest pain are a diagnostic challenge because the majority does not have coronary artery disease (CAD). Assessment of CAD with coronary computed tomography angiography (CCTA) is safe, cost-effective, and accurate, albeit with a modest specificity. Stress myocardial computed tomography perfusion (CTP) has been shown to increase the specificity when added to CCTA, without lowering the sensitivity. This article describes the design of a randomized controlled trial, CATCH-2, comparing a clinical diagnostic management strategy of CCTA alone against CCTA in combination with CTP. Patients with acute-onset chest pain older than 50 years and with at least one cardiovascular risk factor for CAD are being prospectively enrolled to this study from 6 different clinical sites since October 2013. A total of 600 patients will be included. Patients are randomized 1:1 to clinical management based on CCTA or on CCTA in combination with CTP, determining the need for further testing with invasive coronary angiography including measurement of the fractional flow reserve in vessels with coronary artery lesions. Patients are scanned with a 320-row multidetector computed tomography scanner. Decisions to revascularize the patients are taken by the invasive cardiologist independently of the study allocation. The primary end point is the frequency of revascularization. Secondary end points of clinical outcome are also recorded. The CATCH-2 will determine whether CCTA in combination with CTP is diagnostically superior to CCTA alone in the management of patients with acute-onset chest pain. Copyright © 2015 Elsevier Inc. All rights reserved.

Radiation concurrent with gemcitabine for locally advanced head and neck cancer: a phase I trial and intracellular drug incorporation study.

PubMed

Eisbruch, A; Shewach, D S; Bradford, C R; Littles, J F; Teknos, T N; Chepeha, D B; Marentette, L J; Terrell, J E; Hogikyan, N D; Dawson, L A; Urba, S; Wolf, G T; Lawrence, T S

2001-02-01

To examine the feasibility and dose-limiting toxicity (DLT) of once-weekly gemcitabine at doses predicted in preclinical studies to produce radiosensitization, concurrent with a standard course of radiation for locally advanced head and neck cancer. Tumor incorporation of gemcitabine triphosphate (dFdCTP) was measured to assess whether adequate concentrations were achieved at each dose level. Twenty-nine patients with unresectable head and neck cancer received a course of radiation (70 Gy over 7 weeks, 5 days weekly) concurrent with weekly infusions of low-dose gemcitabine. Tumor biopsies were performed after the first gemcitabine infusion (before radiation started), and the intracellular concentrations of dFdCTP were measured. Severe acute and late mucosal and pharyngeal-related DLT required de-escalation of gemcitabine dose in successive patient cohorts receiving dose levels of 300 mg/m(2)/wk, 150 mg/m(2)/wk, and 50 mg/m(2)/wk. No DLT was observed at 10 mg/m(2)/wk. The rate of endoscopy- and biopsy-assessed complete tumor response was 66% to 87% in the various cohorts. Tumor dFdCTP levels were similar in patients receiving 50 to 300 mg/m(2) (on average, 1.55 pmol/mg, SD 1.15) but were barely or not detectable at 10 mg/m(2). A high rate of acute and late mucosa-related DLT and a high rate of complete tumor response were observed in this regimen at the dose levels of 50 to 300 mg/m(2), which also resulted in similar, subcytotoxic intracellular dFdCTP concentrations. These results demonstrate significant tumor and normal tissue radiosensitization by low-dose gemcitabine. Different regimens of combined radiation and gemcitabine should be evaluated, based on newer preclinical data promising an improved therapeutic ratio.

Evaluation of glioblastomas and lymphomas with whole-brain CT perfusion: Comparison between a delay-invariant singular-value decomposition algorithm and a Patlak plot.

PubMed

Hiwatashi, Akio; Togao, Osamu; Yamashita, Koji; Kikuchi, Kazufumi; Yoshimoto, Koji; Mizoguchi, Masahiro; Suzuki, Satoshi O; Yoshiura, Takashi; Honda, Hiroshi

2016-07-01

Correction of contrast leakage is recommended when enhancing lesions during perfusion analysis. The purpose of this study was to assess the diagnostic performance of computed tomography perfusion (CTP) with a delay-invariant singular-value decomposition algorithm (SVD+) and a Patlak plot in differentiating glioblastomas from lymphomas. This prospective study included 17 adult patients (12 men and 5 women) with pathologically proven glioblastomas (n=10) and lymphomas (n=7). CTP data were analyzed using SVD+ and a Patlak plot. The relative tumor blood volume and flow compared to contralateral normal-appearing gray matter (rCBV and rCBF derived from SVD+, and rBV and rFlow derived from the Patlak plot) were used to differentiate between glioblastomas and lymphomas. The Mann-Whitney U test and receiver operating characteristic (ROC) analyses were used for statistical analysis. Glioblastomas showed significantly higher rFlow (3.05±0.49, mean±standard deviation) than lymphomas (1.56±0.53; P<0.05). There were no statistically significant differences between glioblastomas and lymphomas in rBV (2.52±1.57 vs. 1.03±0.51; P>0.05), rCBF (1.38±0.41 vs. 1.29±0.47; P>0.05), or rCBV (1.78±0.47 vs. 1.87±0.66; P>0.05). ROC analysis showed the best diagnostic performance with rFlow (Az=0.871), followed by rBV (Az=0.771), rCBF (Az=0.614), and rCBV (Az=0.529). CTP analysis with a Patlak plot was helpful in differentiating between glioblastomas and lymphomas, but CTP analysis with SVD+ was not. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Efficacy and Safety of the Biosimilar Infliximab CT-P13 Treatment in Inflammatory Bowel Diseases: A Prospective, Multicentre, Nationwide Cohort.

PubMed

Gecse, Krisztina B; Lovász, Barbara D; Farkas, Klaudia; Banai, János; Bene, László; Gasztonyi, Beáta; Golovics, Petra Anna; Kristóf, Tünde; Lakatos, László; Csontos, Ágnes Anna; Juhász, Márk; Nagy, Ferenc; Palatka, Károly; Papp, Mária; Patai, Árpád; Lakner, Lilla; Salamon, Ágnes; Szamosi, Tamás; Szepes, Zoltán; Tóth, Gábor T; Vincze, Áron; Szalay, Balázs; Molnár, Tamás; Lakatos, Péter L

2016-02-01

Biosimilar infliximab CT-P13 is approved for all indications of the originator product in Europe. Prospective data on its efficacy, safety, and immunogenicity in inflammatory bowel diseases are lacking. A prospective, nationwide, multicentre, observational cohort was designed to examine the efficacy, safety, and immunogenicity of CT-P13 infliximab biosimilar in the induction treatment of Crohn's disease [CD] and ulcerative colitis [UC]. Demographic data were collected and a harmonised monitoring strategy was applied. Early clinical remission, response, and early biochemical response were evaluated at Week 14, steroid-free clinical remission was evaluated at Week 30. Therapeutic drug level was monitored using a conventional enzyme-linked immunosorbent assay. In all, 210 consecutive inflammatory bowel disease [126 CD and 84 UC] patients were included in the present cohort. At Week 14, 81.4% of CD and 77.6% of UC patients showed clinical response and 53.6% of CD and 58.6% of UC patients were in clinical remission. Clinical remission rates at Week 14 were significantly higher in CD and UC patients who were infliximab naïve, compared with those with previous exposure to the originator compound [p < 0.05]. Until Week 30, adverse events were experienced in 17.1% of all patients. Infusion reactions and infectious adverse events occurred in 6.6% and 5.7% of all patients, respectively. This prospective multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC. Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Feasibility of dual-low scheme combined with iterative reconstruction technique in acute cerebral infarction volume CT whole brain perfusion imaging.

PubMed

Wang, Tao; Gong, Yi; Shi, Yibing; Hua, Rong; Zhang, Qingshan

2017-07-01

The feasibility of application of low-concentration contrast agent and low tube voltage combined with iterative reconstruction in whole brain computed tomography perfusion (CTP) imaging of patients with acute cerebral infarction was investigated. Fifty-nine patients who underwent whole brain CTP examination and diagnosed with acute cerebral infarction from September 2014 to March 2016 were selected. Patients were randomly divided into groups A and B. There were 28 cases in group A [tube voltage, 100 kV; contrast agent, iohexol (350 mg I/ml), reconstructed by filtered back projection] and 31 cases in group B [tube voltage, 80 kV; contrast agent, iodixanol (270 mg I/ml), reconstructed by algebraic reconstruction technique]. The artery CT value, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), dose length product, effective dose (ED) of radiation and brain iodine intake of both groups were measured and statistically analyzed. Two physicians carried out kappa (κ) analysis on the consistency of image quality evaluation. The difference in subjective image quality evaluation between the groups was tested by χ 2 . The differences in CT value, SNR, CNR, CTP and CT angiography subjective image quality evaluation between both groups were not statistically significant (P>0.05); the diagnosis rate of the acute infarcts between the two groups was not significantly different; while the ED and iodine intake in group B (dual low-dose group) were lower than group A. In conclusion, combination of low tube voltage and iterative reconstruction technique, and application of low-concentration contrast agent (270 mg I/ml) in whole brain CTP examination reduced ED and iodine intake without compromising image quality, thereby reducing the risk of contrast-induced nephropathy.

Intravenous thrombolysis in ischemic stroke with unknown onset using CT perfusion.

PubMed

Cortijo, E; García-Bermejo, P; Calleja, A I; Pérez-Fernández, S; Gómez, R; del Monte, J M; Reyes, J; Arenillas, J F

2014-03-01

Acute ischemic stroke patients with unclear onset time presenting >4.5 h from last-seen-normal (LSN) time are considered late patients and excluded from i.v. thrombolysis. We aimed to evaluate whether this subgroup of patients is different from patients presenting >4.5 h from a witnessed onset, in terms of eligibility and response to computed tomography perfusion (CTP)-guided i.v. thrombolysis. We prospectively studied consecutive acute non-lacunar middle cerebral artery (MCA) ischemic stroke patients presenting >4.5 h from LSN. All patients underwent multimodal CT and were considered eligible for i.v. thrombolysis according to CTP criteria. Two patient groups were established based on the knowledge of the stroke onset time. We compared the proportion of candidates suitable for intravenous thrombolysis between both groups, and their outcome after thrombolytic therapy. Among 147 MCA ischemic stroke patients presenting >4.5 h from LSN, stroke onset was witnessed in 74 and unknown in 73. Thirty-seven (50%) patients in the first group and 32 (44%) in the second met CTP criteria for thrombolysis (P = 0.7). Baseline variables were comparable between both groups with the exception of age, which was higher in the unclear onset group. The rates of early neurological improvement (54.1% vs 46.9%), 2-h MCA recanalization (43.5% vs 37%), symptomatic hemorrhagic transformation (3% vs 0%) and good 3-month functional outcome (62.2% vs 56.3%) did not differ significantly between both groups. Delayed stroke patients with unknown onset time were no different than patients >4.5 h regarding eligibility and response to CTP-based i.v. thrombolysis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Synergistic Use of MODIS and AIRS in a Variational Retrieval of Cloud Parameters.

NASA Astrophysics Data System (ADS)

Li, Jun; Menzel, W. Paul; Zhang, Wenjian; Sun, Fengying; Schmit, Timothy J.; Gurka, James J.; Weisz, Elisabeth

2004-11-01

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.

Molecular characterization of the Salmonella typhi StpA protein that is related to both Yersinia YopE cytotoxin and YopH tyrosine phosphatase.

PubMed

Arricau, N; Hermant, D; Waxin, H; Popoff, M Y

1997-01-01

Analysis of the nucleotide sequence of a 4-kb DNA fragment located between the sip and iag loci on Salmonella typhi chromosome revealed three open reading frames, termed sipF, ctpA and stpA. The 82-amino-acid (aa) sipF product showed extensive similarity to the lacP protein from S. typhimurium. The StpA protein (535 aa) exhibited significant similarity to both Yersinia enterocolitica YopE cytotoxin and YopH tyrosine phosphatase. The CtpA polypeptide (130 aa) might be the molecular chaperone of the StpA protein.

Mechanism of error-free DNA synthesis across N1-methyl-deoxyadenosine by human DNA polymerase-ι

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jain, Rinku; Choudhury, Jayati Roy; Buku, Angeliki

N1-methyl-deoxyadenosine (1-MeA) is formed by methylation of deoxyadenosine at the N1 atom. 1-MeA presents a block to replicative DNA polymerases due to its inability to participate in Watson-Crick (W-C) base pairing. Here we determine how human DNA polymerase-ι (Polι) promotes error-free replication across 1-MeA. Steady state kinetic analyses indicate that Polι is ~100 fold more efficient in incorporating the correct nucleotide T versus the incorrect nucleotide C opposite 1-MeA. To understand the basis of this selectivity, we determined ternary structures of Polι bound to template 1-MeA and incoming dTTP or dCTP. In both structures, template 1-MeA rotates to the synmore » conformation but pairs differently with dTTP versus dCTP. Thus, whereas dTTP partakes in stable Hoogsteen base pairing with 1-MeA, dCTP fails to gain a “foothold” and is largely disordered. Together, our kinetic and structural studies show how Polι maintains discrimination between correct and incorrect incoming nucleotide opposite 1-MeA in preserving genome integrity.« less

Experimental validation of Critical Temperature-Pressure theory of scuffing

NASA Astrophysics Data System (ADS)

Lee, Si C.; Chen, Huanliang

1995-07-01

A series of experiments was conducted for validating a newly developed theory of scuffing. The Critical temperature-Pressure (CTP) theory is based on the physisorption behavior of lubricants and is capable of predicting the onset of scuffing failures over a wide range of operating conditions, including the contacts operating in the boundary lubrication and in the partial elastohydrodynamic lubrication (EHL) regimes. According to the CTP theory, failures occur when the contact temperature exceeds a certain critical value which is a function of the lubricant pressure generated by the hydrodynamic action of the EHL contact. A special device capable of simulating the ambient conditions of the partial EHL conjunctions (of contact temperature, pressure, and the lubricant pressure) was constructed. A ball-on-flat type wear tester was put inside a pressure vessel, completely immersed in a highly pressurized bath of mineral oil. The temperature on the flat specimen was gradually increased while the ball was slowly traversed. At a certain critical temmperature, the friction force abruptly jumped indicating the incipiency of the lubrication breakdown. This experiment was repeated for several levels of hydrostatic pressure and the corresponding critical temperatures were obtained. The test results showed an excellent correlation with the newly developed CTP theory.

Frequency and Voltage Dependence of the Dielectrophoretic Trapping of Short Lengths of DNA and dCTP in a Nanopipette

PubMed Central

Ying, Liming; White, Samuel S.; Bruckbauer, Andreas; Meadows, Lisa; Korchev, Yuri E.; Klenerman, David

2004-01-01

The study of the properties of DNA under high electric fields is of both fundamental and practical interest. We have exploited the high electric fields produced locally in the tip of a nanopipette to probe the motion of double- and single-stranded 40-mer DNA, a 1-kb single-stranded DNA, and a single-nucleotide triphosphate (dCTP) just inside and outside the pipette tip at different frequencies and amplitudes of applied voltages. We used dual laser excitation and dual color detection to simultaneously follow two fluorophore-labeled DNA sequences with millisecond time resolution, significantly faster than studies to date. A strong trapping effect was observed during the negative half cycle for all DNA samples and also the dCTP. This effect was maximum below 1 Hz and decreased with higher frequency. We assign this trapping to strong dielectrophoresis due to the high electric field and electric field gradient in the pipette tip. Dielectrophoresis in electrodeless tapered nanostructures has potential applications for controlled mixing and manipulation of short lengths of DNA and other biomolecules, opening new possibilities in miniaturized biological analysis. PMID:14747337

Advances in Behavioral Laboratory Methods that Inform Tobacco Regulatory Science: A TCORS Working Group Special Issue

PubMed Central

Wright, M. Jerry; Valentine, Gerald

2017-01-01

Objective The 2009 Family Smoking Prevention and Tobacco Control Act (TCA) created unprecented enabling conditions for establishing national regulatory policy that reduces the burden of public health and societal problems associated with tobacco product use. The Center for Tobacco Products (CTP), created by the FDA to implement the TCA, developed a first-of-its-kind FDA/National Institutes of Health (NIH) collaborative program to fund Tobacco Centers of Regulatory Science (TCORS). Methods To assist the TCORS with addressing research priorites, working groups (WGs) comprised of FDA-CTP liasions and TCORS investigators were formed. Under the direction of the Center for Evaluation and Coordination of Trainin and Research (CECTR), the TCORS WGs seek to develop tangible work products in their respective areas of focus. Results The focus of the behavioral pharmacology WG evolved from publishing a narrow paper on behavioral methods in electronic cigarette research to a collection of papers on advances in behavioral laboratory methods that may inform tobacco regulatory science. Conclusion This Special Issue contains articles that address all of the CTP research priorities and demonstrates how advances in behavioral laboratory methods made by TCORS investigators can inform FDA efforst to regulate tobacco products. PMID:29152546

Assessment of Pre- and Post-Operative Cerebral Perfusion in Anterior Circulation Intracranial Aneurysm Clipping Patients at Hospital Sungai Buloh Using CT Perfusion Scan and Correlations to Fisher, Navarro and WFNS Scores.

PubMed

Ghani, Ailani Ab; Nayan, Saiful Azli Mat; Kandasamy, Regunath; Ghani, Abdul Rahman Izani; Rosman, Azmin Kass

2017-02-01

Intracranial aneurysms may rupture and are typically associated with high morbidity and mortality, commonly due to vasospasm after rupture. Once the aneurysm ruptures, the patient's cerebral blood flow may be disturbed during the acute phase, affecting cerebral circulation and thus cerebral perfusion prior to the onset of vasospasm. Fisher and Navarro scores are used to predict vasospasm, while World Federation of Neurosurgical Societies (WFNS) scores are used to predict patient outcomes. Several score modifications are available to obtain higher sensitivity and specificity for the prediction of vasospasm development, but these scores are still unsuccessful. Alternatively, cerebral CT perfusion scan (CTP) is a non-invasive method for measuring cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) in regions of interests (ROI) to obtain the cerebral perfusion status as well as detecting vasospasm. A total of 30 patients' data with clipped anterior circulation intracranial aneurysms admitted to the hospital between 1 January 2013 and 30 June 2014, were collected from the hospital's electronic database. The data collected included patients' admissions demographic profiles, Fisher, Navarro and WFNS scores; and their immediate pre- and post-operative CTP parameters. This study found a significant increase in post-operative MTT (pre- and post-operative MTT) were 9.75 (SD = 1.31) and 10.44 (SD = 1.56) respectively, ( P < 0.001)) as well as a significant reduction in post-operative CBF (pre- and post-operative mean CBF were 195.29 (SD = 24.92) and 179.49 (SD = 31.17) respectively ( P < 0.001)). There were no significant differences in CBV. There were no significant correlations between the pre- and post-operative CTP parameters and Fisher, Navarro or WFNS scores. Despite the interest in using Fisher, Navarro and WFNS scores to predict vasospasm and patient outcomes for ruptured intracranial aneurysms, this study found no significant correlations between these scores in either pre- or post-operative CTP parameters. These results explain the disagreement in the field regarding the multiple proposed grading systems for vasospasm prediction. CTP measures more than just anatomical structures; therefore, it is more sensitive towards minor changes in cerebral perfusion that would not be detected by WFNS, Fisher or Navarro scores.

Ceramic Technology Project data base: September 1992 summary report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keyes, B.L.P.

Data presented in this report represent an intense effort to improve processing methods, testing methods, and general mechanical properties (rupture modulus, tensile, creep, stress-rupture, dynamic and cyclic fatigue, fracture toughness) of candidate ceramics for use in advanced heat engines. This work was performed by many facilities and represents only a small part of the data generated by the Ceramic Technology Project (CTP) since 1986. Materials discussed include GTE PY6, GN-10, NT-154, NT-164, SN-260, SN-251, SN-252, AY6, silicon nitride combined with rare-earth oxides, Y-TZP, ZTA, NC-433, NT-230, Hexoloy SA, MgO-PSZ-to-MgO-PSZ joints, MgO-PSZ-to-cast iron, and a few whisker/fiber-reinforced ceramics. Information in thismore » report was taken from the project`s semiannual and bimonthly progress reports and from final reports summarizing the results of individual studies. Test results are presented in tabular form and in graphs. All data, including test rig descriptions and material characterizations, are stored in the CTP data base and are available to all project participants on request. The objective of this report is to make available the test results from these studies but not to draw conclusions from those data.« less

Synergistic use of MODIS cloud products and AIRS radiance measurements for retrieval of cloud parameters

NASA Astrophysics Data System (ADS)

Li, J.; Menzel, W.; Sun, F.; Schmit, T.

2003-12-01

The Moderate-Resolution Imaging Spectroradiometer (MODIS) and Atmospheric Infrared Sounder (AIRS) measurements from the Earth Observing System's (EOS) Aqua satellite will enable global monitoring of the distribution of clouds. MODIS is able to provide at high spatial resolution (1 ~ 5km) the cloud mask, surface and cloud types, cloud phase, cloud-top pressure (CTP), effective cloud amount (ECA), cloud particle size (CPS), and cloud water path (CWP). AIRS is able to provide CTP, ECA, CPS, and CWP within the AIRS footprint with much better accuracy using its greatly enhanced hyperspectral remote sensing capability. The combined MODIS / AIRS system offers the opportunity for cloud products improved over those possible from either system alone. The algorithm developed was applied to process the AIRS longwave cloudy radiance measurements; results are compared with MODIS cloud products, as well as with the Geostationary Operational Environmental Satellite (GOES) sounder cloud products, to demonstrate the advantage of synergistic use of high spatial resolution MODIS cloud products and high spectral resolution AIRS sounder radiance measurements for optimal cloud retrieval. Data from ground-based instrumentation at the Atmospheric Radiation Measurement (ARM) Program Cloud and Radiation Test Bed (CART) in Oklahoma were used for the validation; results show that AIRS improves the MODIS cloud products in certain cases such as low-level clouds.

Viewing Human DNA Polymerase β Faithfully and Unfaithfully Bypass an Oxidative Lesion by Time-Dependent Crystallography

DOE PAGES

Vyas, Rajan; Reed, Andrew J.; Tokarsky, E. John; ...

2015-03-31

One common oxidative DNA lesion, 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG), is highly mutagenic in vivo due to its anti-conformation forming a Watson–Crick base pair with correct deoxycytidine 5'-triphosphate (dCTP) and its syn-conformation forming a Hoogsteen base pair with incorrect deoxyadenosine 5'-triphosphate (dATP). Here in this article, we utilized time-resolved X-ray crystallography to follow 8-oxoG bypass by human DNA polymerase β (hPolβ). In the 12 solved structures, both Watson–Crick (anti-8-oxoG:anti-dCTP) and Hoogsteen (syn-8-oxoG:anti-dATP) base pairing were clearly visible and were maintained throughout the chemical reaction. Additionally, a third Mg 2+ appeared during the process of phosphodiester bond formation and was located between the reactingmore » α- and β-phosphates of the dNTP, suggesting its role in stabilizing reaction intermediates. After phosphodiester bond formation, hPolβ reopened its conformation, pyrophosphate was released, and the newly incorporated primer 3'-terminal nucleotide stacked, rather than base paired, with 8-oxoG. These structures provide the first real-time pictures, to our knowledge, of how a polymerase correctly and incorrectly bypasses a DNA lesion.« less

Viewing Human DNA Polymerase β Faithfully and Unfaithfully Bypass an Oxidative Lesion by Time-Dependent Crystallography

PubMed Central

Vyas, Rajan; Reed, Andrew J.; Tokarsky, E. John; Suo, Zucai

2015-01-01

One common oxidative DNA lesion, 8-oxo-7,8-dihydro-2′-deoxyguanine (8-oxoG), is highly mutagenic in vivo due to its anti-conformation forming a Watson–Crick base pair with correct deoxycytidine 5′-triphosphate (dCTP) and its syn-conformation forming a Hoogsteen base pair with incorrect deoxyadenosine 5′-triphosphate (dATP). Here, we utilized time-resolved X-ray crystallography to follow 8-oxoG bypass by human DNA polymerase β (hPolβ). In the 12 solved structures, both Watson–Crick (anti-8-oxoG:anti-dCTP) and Hoogsteen (syn-8-oxoG:anti-dATP) base pairing were clearly visible and were maintained throughout the chemical reaction. Additionally, a third Mg2+ appeared during the process of phosphodiester bond formation and was located between the reacting α- and β-phosphates of the dNTP, suggesting its role in stabilizing reaction intermediates. After phosphodiester bond formation, hPolβ reopened its conformation, pyrophosphate was released, and the newly incorporated primer 3′-terminal nucleotide stacked, rather than base paired, with 8-oxoG. These structures provide the first real-time pictures, to our knowledge, of how a polymerase correctly and incorrectly bypasses a DNA lesion. PMID:25825995

Genome-wide re-sequencing of multidrug-resistant Mycobacterium leprae Airaku-3.

PubMed

Singh, P; Benjak, A; Carat, S; Kai, M; Busso, P; Avanzi, C; Paniz-Mondolfi, A; Peter, C; Harshman, K; Rougemont, J; Matsuoka, M; Cole, S T

2014-10-01

Genotyping and molecular characterization of drug resistance mechanisms in Mycobacterium leprae enables disease transmission and drug resistance trends to be monitored. In the present study, we performed genome-wide analysis of Airaku-3, a multidrug-resistant strain with an unknown mechanism of resistance to rifampicin. We identified 12 unique non-synonymous single-nucleotide polymorphisms (SNPs) including two in the transporter-encoding ctpC and ctpI genes. In addition, two SNPs were found that improve the resolution of SNP-based genotyping, particularly for Venezuelan and South East Asian strains of M. leprae. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Tunable multiband plasmonic response of indium antimonide touching microrings in the terahertz range.

PubMed

Moridsadat, Maryam; Golmohammadi, Saeed; Baghban, Hamed

2018-06-01

In this paper, we propose a terahertz (THz) plasmonic structure that supports three resonance modes, including the charge transfer plasmon (CTP), the bonding dipole-dipole plasmon, and the antibonding dipole-dipole plasmon, which can be strongly tuned by geometrical parameters, passively, and the temperature, actively. The structure exhibits a considerable thermal sensitivity of more than 0.01 THz/K. The introduced multiband and tunable THz plasmonic structures offer important applications in thermal switches, thermo-optical modulators, broadband filters, design of multifunctional molecules originating from the multiband specification of the proposed structure, and improvement in plasmonic sensor applications stemming from a detailed study of the CTP mode.

Optical Switching Using Transition from Dipolar to Charge Transfer Plasmon Modes in Ge2Sb2Te5 Bridged Metallodielectric Dimers

PubMed Central

Ahmadivand, Arash; Gerislioglu, Burak; Sinha, Raju; Karabiyik, Mustafa; Pala, Nezih

2017-01-01

Capacitive coupling and direct shuttling of charges in nanoscale plasmonic components across a dielectric spacer and through a conductive junction lead to excitation of significantly different dipolar and charge transfer plasmon (CTP) resonances, respectively. Here, we demonstrate the excitation of dipolar and CTP resonant modes in metallic nanodimers bridged by phase-change material (PCM) sections, material and electrical characteristics of which can be controlled by external stimuli. Ultrafast switching (in the range of a few nanoseconds) between amorphous and crystalline phases of the PCM section (here Ge2Sb2Te5 (GST)) allows for designing a tunable plasmonic switch for optical communication applications with significant modulation depth (up to 88%). Judiciously selecting the geometrical parameters and taking advantage of the electrical properties of the amorphous phase of the GST section we adjusted the extinction peak of the dipolar mode at the telecommunication band (λ~1.55 μm), which is considered as the OFF state. Changing the GST phase to crystalline via optical heating allows for direct transfer of charges through the junction between nanodisks and formation of a distinct CTP peak at longer wavelengths (λ~1.85 μm) far from the telecommunication wavelength, which constitutes the ON state. PMID:28205643

Optical Switching Using Transition from Dipolar to Charge Transfer Plasmon Modes in Ge2Sb2Te5 Bridged Metallodielectric Dimers.

PubMed

Ahmadivand, Arash; Gerislioglu, Burak; Sinha, Raju; Karabiyik, Mustafa; Pala, Nezih

2017-02-16

Capacitive coupling and direct shuttling of charges in nanoscale plasmonic components across a dielectric spacer and through a conductive junction lead to excitation of significantly different dipolar and charge transfer plasmon (CTP) resonances, respectively. Here, we demonstrate the excitation of dipolar and CTP resonant modes in metallic nanodimers bridged by phase-change material (PCM) sections, material and electrical characteristics of which can be controlled by external stimuli. Ultrafast switching (in the range of a few nanoseconds) between amorphous and crystalline phases of the PCM section (here Ge 2 Sb 2 Te 5 (GST)) allows for designing a tunable plasmonic switch for optical communication applications with significant modulation depth (up to 88%). Judiciously selecting the geometrical parameters and taking advantage of the electrical properties of the amorphous phase of the GST section we adjusted the extinction peak of the dipolar mode at the telecommunication band (λ~1.55 μm), which is considered as the OFF state. Changing the GST phase to crystalline via optical heating allows for direct transfer of charges through the junction between nanodisks and formation of a distinct CTP peak at longer wavelengths (λ~1.85 μm) far from the telecommunication wavelength, which constitutes the ON state.

An 80-year summer temperature history from the Xiao Dongkemadi ice core in the central Tibetan Plateau and its association with atmospheric circulation

NASA Astrophysics Data System (ADS)

Li, Xiangying; Ding, Yongjian; Yu, Zhongbo; Mika, Sillanpää; Liu, Shiyin; Shangguan, Donghui; Lu, Chengyang

2015-02-01

The climate significance of oxygen isotopes from the central Tibetan Plateau (cTP) ice cores is a debated issue because of large scale atmospheric circulation. A high-resolution δ18O record was recovered from the Xiao Dongkemadi (XD) ice core, which expanded the spatial coverage of δ18O data in this region. Annual average δ18O correlated significantly with nearby MJJAS air temperatures, suggesting the δ18O can be used as a proxy to reconstruct regional climate change. The reconstructed temperature anomaly is related to the regional and global warming trends, and the greater warming amplitude since 1970s is related to the elevation dependency of the warming signal. The close relationship of the warming to variations in glacier mass balances and discharge reveal that recent warming has led to obvious glacier shrinkage and runoff increase. Correlation analysis suggests that monsoon and westerly moisture substantially influence the cTP ice core records, along with an increase in their level of contribution to the XD core accumulation in recent decades, and confirms a teleconnection of regional climate of the cTP ice cores with climate parameters in the Indian and North Atlantic Oceans.

Crystal Structure of the CTP1L Endolysin Reveals How Its Activity Is Regulated by a Secondary Translation Product*

PubMed Central

Dunne, Matthew; Leicht, Stefan; Krichel, Boris; Thompson, Andrew; Gómez-Torres, Natalia; Garde, Sonia; Narbad, Arjan; Mayer, Melinda J.

2016-01-01

Bacteriophages produce endolysins, which lyse the bacterial host cell to release newly produced virions. The timing of lysis is regulated and is thought to involve the activation of a molecular switch. We present a crystal structure of the activated endolysin CTP1L that targets Clostridium tyrobutyricum, consisting of a complex between the full-length protein and an N-terminally truncated C-terminal cell wall binding domain (CBD). The truncated CBD is produced through an internal translation start site within the endolysin gene. Mutants affecting the internal translation site change the oligomeric state of the endolysin and reduce lytic activity. The activity can be modulated by reconstitution of the full-length endolysin-CBD complex with free CBD. The same oligomerization mechanism applies to the CD27L endolysin that targets Clostridium difficile and the CS74L endolysin that targets Clostridium sporogenes. When the CTP1L endolysin gene is introduced into the commensal bacterium Lactococcus lactis, the truncated CBD is also produced, showing that the alternative start codon can be used in other bacterial species. The identification of a translational switch affecting oligomerization presented here has implications for the design of effective endolysins for the treatment of bacterial infections. PMID:26683375

The Effect of Heart Rate on Exposure Window and Best Phase for Stress Perfusion Computed Tomography: Lessons From the CORE320 Study.

PubMed

Steveson, Chloe; Schuijf, Joanne D; Vavere, Andrea L; Mather, Richard T; Caton, Teresa; Mehra, Vishal; Betoko, Aisha; Cox, Christopher; Lima, Joao Ac; George, Richard T

The aim of this study is to evaluate the effect of heart rate on exposure window, best phase, and image quality for stress computed tomography perfusion (CTP) in the CORE320 study. The CTP data sets were analyzed to determine the best phase for perfusion analysis. A predefined exposure window covering 75% to 95% of the R-R cycle was used. Of the 368 patients included in the analysis, 93% received oral β blockade before the rest scan. The median heart rate during the stress acquisition was 69 bpm (interquartile range [IQR], 60-77). The median best phase was 81% (IQR, 76-90), and length of exposure window was 22% (IQR, 19-24). The best phase was significantly later in the cardiac cycle with higher heart rates (P < 0.001), and higher heart rates resulted in a small, but higher number of poor quality scans (6%, P < 0.001). The median effective dose of the stress scan was 5.3 mSv (IQR, 3.8-6.1). Stress myocardial CTP imaging can be performed using prospective electrocardiography triggering, an exposure window of 75% to 95%, and β-blockade resulting in good or excellent image quality in the majority (80%) of patients while maintaining a low effective radiation dose.

Optical Switching Using Transition from Dipolar to Charge Transfer Plasmon Modes in Ge2Sb2Te5 Bridged Metallodielectric Dimers

NASA Astrophysics Data System (ADS)

Ahmadivand, Arash; Gerislioglu, Burak; Sinha, Raju; Karabiyik, Mustafa; Pala, Nezih

2017-02-01

Capacitive coupling and direct shuttling of charges in nanoscale plasmonic components across a dielectric spacer and through a conductive junction lead to excitation of significantly different dipolar and charge transfer plasmon (CTP) resonances, respectively. Here, we demonstrate the excitation of dipolar and CTP resonant modes in metallic nanodimers bridged by phase-change material (PCM) sections, material and electrical characteristics of which can be controlled by external stimuli. Ultrafast switching (in the range of a few nanoseconds) between amorphous and crystalline phases of the PCM section (here Ge2Sb2Te5 (GST)) allows for designing a tunable plasmonic switch for optical communication applications with significant modulation depth (up to 88%). Judiciously selecting the geometrical parameters and taking advantage of the electrical properties of the amorphous phase of the GST section we adjusted the extinction peak of the dipolar mode at the telecommunication band (λ~1.55 μm), which is considered as the OFF state. Changing the GST phase to crystalline via optical heating allows for direct transfer of charges through the junction between nanodisks and formation of a distinct CTP peak at longer wavelengths (λ~1.85 μm) far from the telecommunication wavelength, which constitutes the ON state.

Tobacco regulatory science: research to inform regulatory action at the Food and Drug Administration's Center for Tobacco Products.

PubMed

Ashley, David L; Backinger, Cathy L; van Bemmel, Dana M; Neveleff, Deborah J

2014-08-01

The U.S. Food and Drug Administration (FDA) promotes the development of regulatory science to ensure that a strong evidence base informs all of its regulatory activities related to the manufacture, marketing, and distribution of tobacco products as well as public education about tobacco product constituents and effects. Toward that end, the FDA's Center for Tobacco Products (CTP) provides funding for research studies with scientific aims that fall within its defined regulatory authority. However, given their traditional biomedical focus on basic and applied research, some researchers may not understand the principles of regulatory science or the types of studies CTP funds. The purpose of this paper is (1) to clarify the definition of regulatory science as a distinct scientific discipline, (2) to explore the role of tobacco regulatory science in order to help researchers understand the parameters and types of research that can be funded by CTP, and (3) to describe the types of research efforts that will inform the FDA's public health framework for tobacco product regulation. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Effects of pyrimidines on the guinea-pig coronary vasculature.

PubMed Central

Vials, A. J.; Burnstock, G.

1993-01-01

1. The effects of the pyrimidines, uridine 5'-triphosphate (UTP), thymidine 5'-triphosphate (TTP) and cytidine 5'-triphosphate (CTP), were examined in the guinea-pig coronary bed, by use of a Langendorff technique. Comparisons were made with the actions of the purines adenosine 5'-triphosphate (ATP), inosine 5'-triphosphate (ITP) and guanosine 5'-triphosphate (GTP). The effect of, the nitric oxide synthase inhibitor, L-NG-nitroarginine methyl ester (L-NAME) and, the prostaglandin synthesis inhibitor, indomethacin on the vasodilator response to these purines and pyrimidines was examined. The effects of these inhibitors were assessed on their ability to inhibit both the amplitude and the area of the vasodilator response. 2. The relative order of potency of the purines and pyrimidines studied was ATP > UTP > ITP >> GTP, TTP, CTP. 3. The maximum amplitude and area of the vasodilator response to the pyrimidines, UTP (5 x 10(-10)-5 x 10(-7) mol), TTP (5 x 10(-8)-5 x 10(-7) mol) and CTP (5 x 10(-7) mol), and purines, ITP (5 x 10(-9)-5 x 10(-7) mol) and GTP (5 x 10(-8)-5 x 10(-7) mol), were significantly reduced by L-NAME (3 x 10(-5) and 10(-4) M).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8298797

Tolbutamide attenuates diazoxide-induced aggravation of hypoxic cell injury.

PubMed

Pissarek, M; Reichelt, C; Krauss, G J; Illes, P

1998-11-23

ATP-dependent potassium (KATP) channels of neurons are closed in the presence of physiological levels of intracellular ATP and open when ATP is depleted during hypoxia or metabolic damage. The present study investigates hypoxic alterations of purine and pyrimidine nucleotide levels supposed to intracellularly modulate KATP channels. In addition, the effects of the KATP channel activator diazoxide and its antagonist tolbutamide were investigated on ATP, GTP, CTP and UTP levels in slices of the parietal cortex. Hypoxia was evoked by saturation of the medium with 95% N2-5% CO2 instead of 95% O2-5% CO2 for 5 min. Nucleotide contents were measured by anion-exchange HPLC in neutralized perchloric acid extracts obtained from slices frozen immediately at the end of incubation. Hypoxia per se decreased purine and pyrimidine nucleoside triphosphate contents. Thus, ATP and GTP contents were reduced to 69.9 and 77.6% of the respective normoxic levels. UTP and CTP contents were even more decreased (to 60.9 and 41.6%),, probably because the salvage pathway of these pyrimidine nucleotides is less effective than that of the purine nucleotides ATP and GTP. While tolbutamide (30 microM) had no effect on the hypoxia-induced decrease of nucleotides, diazoxide at 300, but not 30 microM aggravated the decline of ATP, UTP and CTP to 51.8, 37.5 and 28.5% of the contents observed at normoxia; GTP levels also showed a tendency to decrease after diazoxide application. Tolbutamide (300 microM) antagonized the effects of diazoxide (300 but not 30 microM aggravated the decline of ATP, UTP and CTP to 51.8, 37.5 and 28.5% of the contents observed at normoxia; GTP levels also showed a tendency to decrease after diazoxide application. Tolbutamide (300 microM) antagonized the effects of diazoxide (300 MicroM). Nucleoside diphosphate (ADP, GDP and UDP) levels were uniformly increased by hypoxia. There was no hypoxia-induced increase of ADP contents in the presence of tolbutamide (300 microM). The ATP/ADP, GTP/GDP and UTP/UDP ratios uniformly declined at a low pO2. However, only the ATP/ADP ratio was decreased further by diazoxide (300 microM). The observed alterations in nucleotide contents may be of importance for long- and short-term processes related to acute cerebral hypoxia. Thus, hypoxia-induced alterations of purine and pyrimidine nucleotide levels may influence the open state of KATP-channels during the period of reversible hypoxic cerebral injury. Furthermore, alterations during the irreversible period of cerebral injury may also arise, as a consequence of decreased pyrimidine nucleotide contents affecting cell survival viaprotein and DNA synthesis.

Mechanistic Basis for the Bypass of a Bulky DNA Adduct Catalyzed by a Y-Family DNA Polymerase

PubMed Central

Vyas, Rajan; Efthimiopoulos, Georgia; Tokarsky, E. John; Malik, Chanchal K.; Basu, Ashis K.; Suo, Zucai

2015-01-01

1-Nitropyrene (1-NP), an environmental pollutant, induces DNA damage in vivo and is considered to be carcinogenic. The DNA adducts formed by the 1-NP metabolites stall replicative DNA polymerases but are presumably bypassed by error-prone Y-family DNA polymerases at the expense of replication fidelity and efficiency in vivo. Our running start assays confirmed that a site-specifically placed 8-(deoxyguanosin-N2-yl)-1-aminopyrene (dG1,8), one of the DNA adducts derived from 1-NP, can be bypassed by Sulfolobus solfataricus DNA polymerase IV (Dpo4), although this representative Y-family enzyme was paused strongly by the lesion. Pre-steady-state kinetic assays were employed to determine the low nucleotide incorporation fidelity and establish a minimal kinetic mechanism for the dG1,8 bypass by Dpo4. To reveal a structural basis for dCTP incorporation opposite dG1,8, we solved the crystal structures of the complexes of Dpo4 and DNA containing a templating dG1,8 lesion in the absence or presence of dCTP. The Dpo4·DNA-dG1,8 binary structure shows that the aminopyrene moiety of the lesion stacks against the primer/template junction pair, while its dG moiety projected into the cleft between the Finger and Little Finger domains of Dpo4. In the Dpo4·DNA-dG1,8·dCTP ternary structure, the aminopyrene moiety of the dG1,8 lesion, is sandwiched between the nascent and junction base pairs, while its base is present in the major groove. Moreover, dCTP forms a Watson–Crick base pair with dG, two nucleotides upstream from the dG1,8 site, creating a complex for “-2” frameshift mutation. Mechanistically, these crystal structures provide additional insight into the aforementioned minimal kinetic mechanism. PMID:26327169

Inactivation of Lactobacillus leichmannii ribonucleotide reductase by 2',2'-difluoro-2'-deoxycytidine 5'-triphosphate: adenosylcobalamin destruction and formation of a nucleotide-based radical.

PubMed

Lohman, Gregory J S; Gerfen, Gary J; Stubbe, Joanne

2010-02-23

Ribonucleotide reductase (RNR, 76 kDa) from Lactobacillus leichmannii is a class II RNR that requires adenosylcobalamin (AdoCbl) as a cofactor. It catalyzes the conversion of nucleoside triphosphates to deoxynucleotides and is 100% inactivated by 1 equiv of 2',2'-difluoro-2'-deoxycytidine 5'-triphosphate (F(2)CTP) in <2 min. Sephadex G-50 chromatography of the inactivation reaction mixture for 2 min revealed that 0.47 equiv of a sugar moiety is covalently bound to RNR and 0.25 equiv of a cobalt(III) corrin is tightly associated, likely through a covalent interaction with C(419) (Co-S) in the active site of RNR [Lohman, G. J. S., and Stubbe, J. (2010) Biochemistry 49, DOI: 10.1021/bi902132u ]. After 1 h, a similar experiment revealed 0.45 equiv of the Co-S adduct associated with the protein. Thus, at least two pathways are associated with RNR inactivation: one associated with alkylation by the sugar of F(2)CTP and the second with AdoCbl destruction. To determine the fate of [1'-(3)H]F(2)CTP in the latter pathway, the reaction mixture at 2 min was reduced with NaBH(4) (NaB(2)H(4)) and the protein separated from the small molecules using a centrifugation device. The small molecules were dephosphorylated and analyzed by HPLC to reveal 0.25 equiv of a stereoisomer of cytidine, characterized by mass spectrometry and NMR spectroscopy, indicating the trapped nucleotide had lost both of its fluorides and gained an oxygen. High-field ENDOR studies with [1'-(2)H]F(2)CTP from the reaction quenched at 30 s revealed a radical that is nucleotide-based. The relationship between this radical and the trapped cytidine analogue provides insight into the nonalkylative pathway for RNR inactivation relative to the alkylative pathway.

A novel method for quantification of gemcitabine and its metabolites 2',2'-difluorodeoxyuridine and gemcitabine triphosphate in tumour tissue by LC-MS/MS: comparison with (19)F NMR spectroscopy.

PubMed

Bapiro, Tashinga E; Richards, Frances M; Goldgraben, Mae A; Olive, Kenneth P; Madhu, Basetti; Frese, Kristopher K; Cook, Natalie; Jacobetz, Michael A; Smith, Donna-Michelle; Tuveson, David A; Griffiths, John R; Jodrell, Duncan I

2011-11-01

To develop a sensitive analytical method to quantify gemcitabine (2',2'-difluorodeoxycytidine, dFdC) and its metabolites 2',2'-difluorodeoxyuridine (dFdU) and 2',2'-difluorodeoxycytidine-5'-triphosphate (dFdCTP) simultaneously from tumour tissue. Pancreatic ductal adenocarcinoma tumour tissue from genetically engineered mouse models of pancreatic cancer (KP ( FL/FL ) C and KP ( R172H/+) C) was collected after dosing the mice with gemcitabine. (19)F NMR spectroscopy and LC-MS/MS protocols were optimised to detect gemcitabine and its metabolites in homogenates of the tumour tissue. A (19)F NMR protocol was developed, which was capable of distinguishing the three analytes in tumour homogenates. However, it required at least 100 mg of the tissue in question and a long acquisition time per sample, making it impractical for use in large PK/PD studies or clinical trials. The LC-MS/MS protocol was developed using porous graphitic carbon to separate the analytes, enabling simultaneous detection of all three analytes from as little as 10 mg of tissue, with a sensitivity for dFdCTP of 0.2 ng/mg tissue. Multiple pieces of tissue from single tumours were analysed, showing little intra-tumour variation in the concentrations of dFdC or dFdU (both intra- and extra-cellular). Intra-tumoural variation was observed in the concentration of dFdCTP, an intra-cellular metabolite, which may reflect regions of different cellularity within a tumour. We have developed a sensitive LC-MS/MS method capable of quantifying gemcitabine, dFdU and dFdCTP in pancreatic tumour tissue. The requirement for only 10 mg of tissue enables this protocol to be used to analyse multiple areas from a single tumour and to spare tissue for additional pharmacodynamic assays.

Systematic review with meta-analysis: the efficacy and safety of CT-P13, a biosimilar of anti-tumour necrosis factor-α agent (infliximab), in inflammatory bowel diseases.

PubMed

Komaki, Y; Yamada, A; Komaki, F; Micic, D; Ido, A; Sakuraba, A

2017-04-01

Biosimilars of anti-tumour necrosis factor (TNF)-α agents have now become clinically available for the treatment of inflammatory bowel diseases (IBD). To perform a systematic review and meta-analysis to evaluate the efficacy and safety of biosimilars of anti-TNF-α agents in patients with IBD. Electronic databases were searched. The outcomes were the pooled rates of clinical response or remission, sustained clinical response or remission, and adverse events in patients with IBD induced with or switched to biosimilars of anti-TNF-α agents. Eleven observational studies reporting outcomes in 829 patients treated with biosimilar of infliximab (CT-P13) were identified. The pooled rates of clinical response among Crohn's disease (CD) and ulcerative colitis (UC) at 8-14 weeks were 0.79 (95% confidence interval (CI) = 0.65-0.88) and 0.74 (95% CI = 0.65-0.82), respectively, and at 24-30 weeks were 0.77 (95% CI = 0.63-0.86) and 0.77 (95% CI = 0.67-0.85) respectively. Adverse events were rare (CD, 0.08 (95% CI = 0.02-0.26); UC, 0.08 (95% CI = 0.03-0.17)). The pooled rates of sustained clinical response among CD and UC after switching from infliximab to CT-P13 at 30-32 weeks were 0.85 (95% CI = 0.71-0.93) and 0.96 (95% CI = 0.58-1.00), respectively, and at 48-63 weeks were 0.75 (95% CI = 0.44-0.92) and 0.83 (95% CI = 0.19-0.99) respectively. Adverse events were rare (CD, 0.10, 95% CI = 0.02-0.31; UC, 0.22, 95% CI = 0.04-0.63). CT-P13 was associated with excellent clinical efficacy and safety profile, supporting its use in the treatment of IBD. © 2017 John Wiley & Sons Ltd.

Control and monitoring method and system for electromagnetic forming process

DOEpatents

Kunerth, Dennis C.; Lassahn, Gordon D.

1990-01-01

A process, system, and improvement for a process for electromagnetic forming of a workpiece in which characteristics of the workpiece such as its geometry, electrical conductivity, quality, and magnetic permeability can be determined by monitoring the current and voltage in the workcoil. In an electromagnet forming process in which a power supply provides current to a workcoil and the electromagnetic field produced by the workcoil acts to form the workpiece, the dynamic interaction of the electromagnetic fields produced by the workcoil with the geometry, electrical conductivity, and magnetic permeability of the workpiece, provides information pertinent to the physical condition of the workpiece that is available for determination of quality and process control. This information can be obtained by deriving in real time the first several time derivatives of the current and voltage in the workcoil. In addition, the process can be extended by injecting test signals into the workcoil during the electromagnetic forming and monitoring the response to the test signals in the workcoil.

Application of silver nanoparticles to the chemiluminescence determination of cefditoren pivoxil using the luminol-ferricyanide system.

PubMed

Alarfaj, Nawal A; Aly, Fatma A; El-Tohamy, Maha F

2015-02-01

A new simple, accurate and sensitive sequential injection analysis chemiluminescence (CL) detection method for the determination of cefditoren pivoxil (CTP) has been developed. The developed method was based on the enhancement effect of silver nanoparticles on the CL signal arising from a luminol-potassium ferricyanide reaction in the presence of CTP. The optimum conditions relevant to the effect of luminol, potassium ferricyanide and silver nanoparticle concentrations were investigated. The proposed method showed linear relationships between relative CL intensity and the investigated drug concentration at the range 0.001-5000 ng/mL, (r = 0.9998, n = 12) with a detection limit of 0.5 pg/mL and quantification limit of 0.001 ng/mL. The relative standard deviation was 1.6%. The proposed method was employed for the determination of CTP in bulk drug, in its pharmaceutical dosage forms and biological fluids such as human serum and urine. The interference of some common additive compounds such as glucose, lactose, starch, talc and magnesium stearate was investigated. In addition, the interference of some related cephalosporins was tested. No interference was recorded. The obtained sequential injection analysis-CL results were statistically compared with those from a reported method and did not show any significant differences. Copyright © 2014 John Wiley & Sons, Ltd.

A potyvirus vector efficiently targets recombinant proteins to chloroplasts, mitochondria and nuclei in plant cells when expressed at the amino terminus of the polyprotein.

PubMed

Majer, Eszter; Navarro, José-Antonio; Daròs, José-Antonio

2015-09-01

Plant virus-based expression systems allow quick and efficient production of recombinant proteins in plant biofactories. Among them, a system derived from tobacco etch virus (TEV; genus potyvirus) permits coexpression of equimolar amounts of several recombinant proteins. This work analyzed how to target recombinant proteins to different subcellular localizations in the plant cell using this system. We constructed TEV clones in which green fluorescent protein (GFP), with a chloroplast transit peptide (cTP), a nuclear localization signal (NLS) or a mitochondrial targeting peptide (mTP) was expressed either as the most amino-terminal product or embedded in the viral polyprotein. Results showed that cTP and mTP mediated efficient translocation of GFP to the corresponding organelle only when present at the amino terminus of the viral polyprotein. In contrast, the NLS worked efficiently at both positions. Viruses expressing GFP in the amino terminus of the viral polyprotein produced milder symptoms. Untagged GFPs and cTP and NLS tagged amino-terminal GFPs accumulated to higher amounts in infected tissues. Finally, viral progeny from clones with internal GFPs maintained the extra gene better. These observations will help in the design of potyvirus-based vectors able to coexpress several proteins while targeting different subcellular localizations, as required in plant metabolic engineering. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The USC Adult Twin Cohorts: International Twin Study and California Twin Program.

PubMed

Cozen, Wendy; Hwang, Amie E; Cockburn, Myles G; Hamilton, Ann S; Zadnick, John; Mack, Thomas M

2013-02-01

The study of twin subjects permits the documentation of crude heritability and may promote the identification of specific causal alleles. We believe that at the current time, the chief research advantage of twins as subjects, especially monozygotic twins, is that the commonality of their genetic and cultural identity simplifies the interpretation of biological associations. In order to study genetic and environmental determinants of cancer and chronic diseases, we developed two twin registries, maintained at the University of Southern California: The International Twin Study (ITS) and the California Twin Program (CTP). The ITS is a volunteer registry of twins with cancer and chronic disease consisting of 17,245 twin pairs affected by cancer and chronic disease, respectively, ascertained by advertising in periodicals from 1980-1991. The CTP is a population-based registry of California-born twin pairs ascertained by linking the California birth records to the State Department of Motor Vehicles. Over 51,000 individual California twins representing 36,965 pairs completed and returned 16-page questionnaires. Cancer diagnoses in the California twins are updated by regular linkage to the California Cancer Registry. Over 5,000 cancer patients are represented in the CTP. Twins from both registries have participated extensively in studies of breast cancer, melanoma, lymphoma, multiple sclerosis, systemic lupus erythematosus, diabetes mellitus type 1, mammographic density, smoking, and other traits and conditions.

Relative cerebral blood volume is associated with collateral status and infarct growth in stroke patients in SWIFT PRIME.

PubMed

Arenillas, Juan F; Cortijo, Elisa; García-Bermejo, Pablo; Levy, Elad I; Jahan, Reza; Goyal, Mayank; Saver, Jeffrey L; Albers, Gregory W

2017-01-01

We aimed to evaluate how predefined candidate cerebral perfusion parameters correlate with collateral circulation status and to assess their capacity to predict infarct growth in patients with acute ischemic stroke (AIS) eligible for endovascular therapy. Patients enrolled in the SWIFT PRIME trial with baseline computed tomography perfusion (CTP) scans were included. RAPID software was used to calculate mean relative cerebral blood volume (rCBV) in hypoperfused regions, and hypoperfusion index ratio (HIR). Blind assessments of collaterals were performed using CT angiography in the whole sample and cerebral angiogram in the endovascular group. Reperfusion was assessed on 27-h CTP; infarct volume was assessed on 27-h magnetic resonance imaging/CT scans. Logistic and rank linear regression models were conducted. We included 158 patients. High rCBV ( p = 0.03) and low HIR ( p = 0.03) were associated with good collaterals. A positive association was found between rCBV and better collateral grades on cerebral angiography ( p = 0.01). Baseline and 27-h follow-up CTP were available for 115 patients, of whom 74 (64%) achieved successful reperfusion. Lower rCBV predicted a higher infarct growth in successfully reperfused patients ( p = 0.038) and in the endovascular treatment group ( p = 0.049). Finally, rCBV and HIR may serve as markers of collateral circulation in AIS patients prior to endovascular therapy. Unique identifier: NCT0165746.

Electromagnetic Spectrum Test and Evaluation Process

DTIC Science & Technology

2010-01-01

HERO , hazards of electromagnetic radiation to ordnance ; HERP, hazards of electromagnetic radiation to personnel; HERF, hazards of electromagnetic ... electromagnetic pulse (EMP); electronic protection; electrostatic dis- charge (ESD); hazards of electromagnetic radi- ation to personnel (HERP), ordnance ...including ordnance containing electrically initiated devices, to be mutually compatible in their intended

CTP synthase forms the cytoophidium in human hepatocellular carcinoma.

PubMed

Chang, Chia-Chun; Jeng, Yung-Ming; Peng, Min; Keppeke, Gerson Dierley; Sung, Li-Ying; Liu, Ji-Long

2017-12-15

CTP synthase (CTPS) can aggregate into an intracellular macrostructure, the cytoophidium, in various organisms including human cells. Previous studies have shown that assembly of human CTPS cytoophidia may be correlated with the cellular metabolic status, and is able to promote the activity of CTPS. A correlation between the cytoophidium and cancer metabolism has been proposed but not yet been revealed. In the current study we provide clear evidence of the presence of CTPS cytoophidia in various human cancers and some non-cancerous tissues. Moreover, among 203 tissue samples of hepatocellular carcinoma, 56 (28%) samples exhibited many cytoophidia, whereas no cytoophidia were detected in adjacent non-cancerous hepatocytes for all samples. Our findings suggest that the CTPS cytoophidium may participate in the adaptive metabolism of human hepatocellular carcinoma. Copyright © 2017. Published by Elsevier Inc.

Quantifying Electromagnetic Wave Propagation Environment Using Measurements From A Small Buoy

DTIC Science & Technology

2017-06-01

ELECTROMAGNETIC WAVE PROPAGATION ENVIRONMENT USING MEASUREMENTS FROM A SMALL BUOY by Andrew E. Sweeney June 2017 Thesis Advisor: Qing Wang...TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE QUANTIFYING ELECTROMAGNETIC WAVE PROPAGATION ENVIRONMENT USING MEASUREMENTS FROM A...the Coupled Air Sea Processes and Electromagnetic (EM) ducting Research (CASPER), to understand air-sea interaction processes and their representation

How Y-Family DNA polymerase IV is more accurate than Dpo4 at dCTP insertion opposite an N2-dG adduct of benzo[a]pyrene.

PubMed

Sholder, Gabriel; Creech, Amanda; Loechler, Edward L

2015-11-01

To bypass DNA damage, cells have Y-Family DNA polymerases (DNAPs). One Y-Family-class includes DNAP κ and DNAP IV, which accurately insert dCTP opposite N(2)-dG adducts, including from the carcinogen benzo[a]pyrene (BP). Another class includes DNAP η and DNAP V, which insert accurately opposite UV-damage, but inaccurately opposite BP-N(2)-dG. To investigate structural differences between Y-Family-classes, regions are swapped between DNAP IV (a κ/IV-class-member) and Dpo4 (a η/V-class-member); the kinetic consequences are evaluated via primer-extension studies with a BP-N(2)-dG-containing template. Four key structural elements are revealed. (1) Y-Family DNAPs have discreet non-covalent contacts between their little finger-domain (LF-Domain) and their catalytic core-domain (CC-Domain), which we call "non-covalent bridges" (NCBs). Arg37 and Arg38 in DNAP IV's CC-Domain near the active site form a non-covalent bridge (AS-NCB) by interacting with Glu251 and Asp252, respectively, in DNAP IV's LF-Domain. Without these interactions dATP/dGTP/dTTP misinsertions increase. DNAP IV's AS-NCB suppresses misinsertions better than Dpo4's equivalent AS-NCB. (2) DNAP IV also suppresses dATP/dGTP/dTTP misinsertions via a second non-covalent bridge, which is ∼8Å from the active site (Distal-NCB). Dpo4 has no Distal-NCB, rendering it inferior at dATP/dGTP/dTTP suppression. (3) dCTP insertion is facilitated by the larger minor groove opening near the active site in DNAP IV versus Dpo4, which is sensible given that Watson/Crick-like [dCTP:BP-N(2)-dG] pairing requires the BP-moiety to be in the minor groove. (4) Compared to Dpo4, DNAP IV has a smaller major groove opening, which suppresses dGTP misinsertion, implying BP-N(2)-dG bulk in the major groove during Hoogsteen syn-adduct-dG:dGTP pairing. In summary, DNAP IV has a large minor groove opening to enhance dCTP insertion, a plugged major groove opening to suppress dGTP misinsertion, and two non-covalent bridges (near and distal to the active site) to suppress dATP/dGTP/dTTP misinsertions; collectively these four structural features enhance DNAP IV's dNTP insertion fidelity opposite a BP-N(2)-dG adduct compared to Dpo4. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison between target magnetic resonance imaging (MRI) in-gantry and cognitively directed transperineal or transrectal-guided prostate biopsies for Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 MRI lesions.

PubMed

Yaxley, Anna J; Yaxley, John W; Thangasamy, Isaac A; Ballard, Emma; Pokorny, Morgan R

2017-11-01

To compare the detection rates of prostate cancer (PCa) in men with Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 abnormalities on 3-Tesla multiparametric (mp) magnetic resonance imaging (MRI) using in-bore MRI-guided biopsy compared with cognitively directed transperineal (cTP) biopsy and transrectal ultrasonography (cTRUS) biopsy. This was a retrospective single-centre study of consecutive men attending the private practice clinic of an experienced urologist performing MRI-guided biopsy and an experienced urologist performing cTP and cTRUS biopsy techniques for PI-RADS 3-5 lesions identified on 3-Tesla mpMRI. There were 595 target mpMRI lesions from 482 men with PI-RADS 3-5 regions of interest during 483 episodes of biopsy. The abnormal mpMRI target lesion was biopsied using the MRI-guided method for 298 biopsies, the cTP method for 248 biopsies and the cTRUS method for 49 biopsies. There were no significant differences in PCa detection among the three biopsy methods in PI-RADS 3 (48.9%, 40.0% and 44.4%, respectively), PI-RADS 4 (73.2%, 81.0% and 85.0%, respectively) or PI-RADS 5 (95.2, 92.0% and 95.0%, respectively) lesions, and there was no significant difference in detection of significant PCa among the biopsy methods in PI-RADS 3 (42.2%, 30.0% and 33.3%, respectively), PI-RADS 4 (66.8%, 66.0% and 80.0%, respectively) or PI-RADS 5 (90.5%, 89.8% and 90.0%, respectively) lesions. There were also no differences in PCa or significant PCa detection based on lesion location or size among the methods. We found no significant difference in the ability to detect PCa or significant PCa using targeted MRI-guided, cTP or cTRUS biopsy methods. Identification of an abnormal area on mpMRI appears to be more important in increasing the detection of PCa than the technique used to biopsy an MRI abnormality. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Different scoring systems to predict 6-week mortality in cirrhosis patients with acute variceal bleeding: a retrospective analysis of 202 patients.

PubMed

Wang, Fang; Cui, Shu; Wang, Fengmei; Li, Fenghui; Tang, Fei; Zhang, Xu; Gao, Yanying; Lv, Hongmin

2018-06-17

Determine the optimal scoring system for evaluation of 6-week bleeding-related mortality in liver cirrhosis patients with acute variceal bleeding (AVB). Prediction effects of six scoring systems, AIMS65 score, Glasgow-Blatchford (GBS) score, full Rockall (FRS) score, the model for end-stage liver disease (MELD), the MELD-Na model and the Child-Turcotte-Pugh (CTP) score were analyzed in this study. A total of 202 liver cirrhosis patients with AVB were enrolled between 1 January 2014, and 31 December 2014. All subjects were scored according to AIMS65, GBS, FRS, MELD, MELD-Na and CTP scoring systems on the first day of admission. The primary endpoint of the study was 6-week mortality. The prediction effect of these scoring systems for 6-week mortality was compared by ROC curve and the area under the curve (AUC). The scores of nonsurvival group evaluated by the AIMS65, GBS, FRS, MELD, MELD-Na and CTP (2.6 ± 1.1, 12.9 ± 2.7, 6.6 ± 1.8, 26.9 ± 6.5, 31.6 ± 9.3, 9.6 ± 2.2, respectively) were higher than those of the survival group (1.2 ± 1.1, 10.2 ± 3.4, 5.1 ± 1.6, 21.0 ± 6.4, 22.8 ± 8.2, 7.7 ± 2.0, respectively) (p < .01). The values of AUC and Youden index of AIMS65 and MELD-Na scoring systems [(0.808, 0.453) and (0.781, 0.516), respectively] were superior to those of MELD (0.761, 0.454), CTP (0.748, 0.399), FRS (0.738, 0.358) and GBS scoring systems (0.726, 0.370). AIMS65 and MELD-Na scoring systems are recommended for evaluation of 6-week bleeding-related mortality in liver cirrhosis patients with AVB.

“Gate-keeper” Residues and Active-Site Rearrangements in DNA Polymerase μ Help Discriminate Non-cognate Nucleotides

PubMed Central

Li, Yunlang; Schlick, Tamar

2013-01-01

Incorporating the cognate instead of non-cognate substrates is crucial for DNA polymerase function. Here we analyze molecular dynamics simulations of DNA polymerase μ (pol μ) bound to different non-cognate incoming nucleotides including A:dCTP, A:dGTP, A(syn):dGTP, A:dATP, A(syn):dATP, T:dCTP, and T:dGTP to study the structure-function relationships involved with aberrant base pairs in the conformational pathway; while a pol μ complex with the A:dTTP base pair is available, no solved non-cognate structures are available. We observe distinct differences of the non-cognate systems compared to the cognate system. Specifically, the motions of active-site residue His329 and Asp330 distort the active site, and Trp436, Gln440, Glu443 and Arg444 tend to tighten the nucleotide-binding pocket when non-cognate nucleotides are bound; the latter effect may further lead to an altered electrostatic potential within the active site. That most of these “gate-keeper” residues are located farther apart from the upstream primer in pol μ, compared to other X family members, also suggests an interesting relation to pol μ's ability to incorporate nucleotides when the upstream primer is not paired. By examining the correlated motions within pol μ complexes, we also observe different patterns of correlations between non-cognate systems and the cognate system, especially decreased interactions between the incoming nucleotides and the nucleotide-binding pocket. Altered correlated motions in non-cognate systems agree with our recently proposed hybrid conformational selection/induced-fit models. Taken together, our studies propose the following order for difficulty of non-cognate system insertions by pol μ: T:dGTP

Transit management certificate program.

DOT National Transportation Integrated Search

2012-07-01

TTI worked closely with the Landscape Architecture and Urban Planning Department : (LAUP) of Texas A&M University (TAMU) to develop a transit management certificate : focus for the current Graduate Certificate in Transportation Planning (CTP) housed ...

A letter of intent for an experiment to study strong electromagnetic fields at RHIC via multiple electromagnetic processes

NASA Technical Reports Server (NTRS)

Fatyga, M.; Norbury, John W.

1992-01-01

An experimental program at the Relativistic Heavy Ion Collider (RHIC) which is designed to study nonperturbative aspects of electrodynamics is outlined. Additional possibilities for new studies of electrodynamics via multiple electromagnetic processes are also described.

Regulation of PRPP and nucleoside tri and tetraphosphate pools in Escherichia coli under conditions of nitrogen starvation.

PubMed Central

Villadsen, I S; Michelsen, O

1977-01-01

The ribonucleoside triphosphate, deoxyribonucleoside triphosphate, 3' -diphosphate guanosine 5' -diphosphate (ppGpp), and 5-phosphoribosyl 1-pyrophosphate (PRPP) pools in Escherichia coli B were determined by thin-layer chromatography during changing conditions to ammonium starvation. The intracellular concentrations of all nucleotides were found to change in a well-defined order several minutes before andy observed change in the optical density of the culture. The levels of purine nucleoside triphosphates (adenosine 5' -triphosphate [CTP], dCTP) and uridine nucleotides (uridine 5' -triphosphate, deoxythymidine 5'-triphosphate). The deoxyribonucleotides thus behaved as the ribonucleotides. The levels of ppGpp increased 11-fold after the decrease in uridine nucleotides, when the accumulation of stable ribonucleic acid (RNA) stopped. The level of the nucleotide pool did not stabilize until 30 min after the change in optical density. The pool of dGTP dropped concomitantly with the pool of CTP. The nucleotide precursor PRPP exhibited a transient increase, wtih maximum value of four times the exponential levels at the onset of starvation. Apparently the cell adjusts early to starvation by reducing either the phosphorylating activity or the nucleotide biosynthetic activity. As in other downshift systems, the accumulation of stable RNA stopped before the break in optical density and before the stop in protein accumulation. Cell divisions were quite insensitive to the control mechanisms operating on RNA and protein accumulation under ammonium starvation, since the cells continued to divide for 21 min without any net accumulation of RNA. Images PMID:323222

Cerebral Hypoperfusion in Posterior Reversible Encephalopathy Syndrome is Different from Transient Ischemic Attack on CT Perfusion.

PubMed

Vanacker, Peter; Matias, Gonçalo; Hagmann, Patric; Michel, Patrik

2015-01-01

PRES is a reversible neurotoxic state presenting with headache, altered mental status, visual loss, and seizures. Delayed diagnosis can be avoided if radiological patterns could distinguish PRES from cerebral ischemia. Clinical and radiological data were collected on all hospitalized patients who had (1) discharge diagnosis of PRES and (2) acute CTP/CTA. Data were compared with 10 TIA patients with proven cytotoxic edema on MRI. Of the four PRES patients found, three were correlated with acute blood pressure and one with chemotherapy. At the radiological level, quantitative analyses of the CTP parameters showed that 2 out of 4 patients had bilaterally reduced CBF-values (23.2-47.1 ml/100g/min) in occipital regions, as seen in the pathological regions of TIA patients (27.3 ± 13.5 ml/100g/min). When compared with TIA patients, the pathological ROI's demonstrated decreased CBV-values (3.4-5.6 ml/100g). Vasogenic edema on MRI FLAIR imaging was seen in only one PRES patient, and cytotoxic edema on DWI-imaging was never found. CT angiography showed in one PRES patient a vasospasm-like unilateral posterior cerebral artery. If confirmed by other groups, CTP and CTA imaging in patients with acute visual loss and confusion may help to distinguish PRES from bi-occipital ischemia. These radiological parameters may identify PRES patients at risk for additional tissue infarction. Copyright © 2014 by the American Society of Neuroimaging.

Effect of oxybuprocaine eye drops on corneal volume and thickness measurements.

PubMed

Rosa, Nicola; De Bernardo, Maddalena; Borrelli, Maria; Filosa, Maria Luisa; Lanza, Michele

2011-05-01

To investigate the effect of oxybuprocaine eye drops on corneal volume (CV) and corneal thickness measurements. Central corneal thickness (CCT), corneal thinnest point (CTP), and CV of 78 eyes of 78 healthy volunteers were measured with Pentacam, before and 5 min after the administration of oxybuprocaine eye drops. The fellow non-anesthetized eyes were used as control. Before topical anesthesia, the mean CCT was 546.76 ± 35.3 μm, after anesthesia, it was 547.76 ± 36.56 μm (p = 0.86). In the fellow eyes, the first mean CCT was 548.82 ± 35.2 μm and the second was 547.55 ± 35.9 μm (p = 0.82). The mean CTP before anesthesia was 543.99 ± 35.23 μm, after it was 544.89 ± 36.3 μm (p = 0.88). In the fellow eyes, the first mean CTP was 544.15 ± 35.35 μm and the second was 542.81 ± 36 μm (p = 0.81). Before topical anesthesia, the mean CV was 60.55 ± 3.84 mm, after it was 60.66 ± 3.97 mm (p = 0.86). In the fellow eyes, the first mean CV was 60.93 ± 3.87 mm and the second was 60.73 ± 4 mm (p = 0.75). Oxybuprocaine eye drops do not appear to induce a significant corneal swelling and do not affect the measurements when comparing CCT measured with optical or ultrasound devices.

Improvement in thin cirrus retrievals using an emissivity-adjusted CO2 slicing algorithm

NASA Astrophysics Data System (ADS)

Zhang, Hong; Menzel, W. Paul

2002-09-01

CO2 slicing has been generally accepted as a useful algorithm for determining cloud top pressure (CTP) and effective cloud amount (ECA) for tropospheric clouds above 600 hPa. To date, the technique has assumed that the surface emissivity is that of a blackbody in the long-wavelength infrared radiances and that the cloud emissivities in spectrally close bands are approximately equal. The modified CO2 slicing algorithm considers adjustments of both surface emissivity and cloud emissivity ratio. Surface emissivity is adjusted according to the surface types. The ratio of cloud emissivities in spectrally close bands is adjusted away from unity according to radiative transfer calculations. The new CO2 slicing algorithm is examined with Moderate Resolution Imaging Spectroradiometer (MODIS) Airborne Simulator (MAS) CO2 band radiance measurements over thin clouds and validated against Cloud Lidar System (CLS) measurements of the same clouds; it is also applied to Geostationary Operational Environmental Satellite (GOES) Sounder data to study the overall impact on cloud property determinations. For high thin clouds an improved product emerges, while for thick and opaque clouds there is little change. For very thin clouds, the CTP increases by about 10-20 hPa and RMS (root mean square bias) difference is approximately 50 hPa; for thin clouds, the CTP increase is about 10 hPa bias and RMS difference is approximately 30 hPa. The new CO2 slicing algorithm places the clouds lower in the troposphere.

Review article: scoring systems for assessing prognosis in critically ill adult cirrhotics.

PubMed

Cholongitas, E; Senzolo, M; Patch, D; Shaw, S; Hui, C; Burroughs, A K

2006-08-01

Cirrhotic patients admitted to intensive care units (ICU) still have poor outcomes. Some current ICU prognostic models [Acute Physiology and Chronic Health Evaluation (APACHE), Organ System Failure (OSF) and Sequential Organ Failure Assessment (SOFA)] were used to stratify cirrhotics into risk categories, but few cirrhotics were included in the original model development. Liver-specific scores [Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD)] could be useful in this setting. To evaluate whether ICU prognostic models perform better compared with liver-disease specific ones in cirrhotics admitted to ICU. We performed a structured literature review identifying clinical studies focusing on prognosis and risk factors for mortality in adult cirrhotics admitted to ICU. We found 21 studies (five solely dealing with gastrointestinal bleeding) published during the last 20 years (54-420 patients in each). APACHE II and III, SOFA and OSF had better discrimination for correctly predicting death compared with the CTP score. The MELD score was evaluated only in one study and had good predictive accuracy [receiver operator characteristic (ROC) curve: 0.81). Organ dysfunction models (OSF, SOFA) were superior compared with APACHE II and III (ROC curve: range 0.83-0.94 vs. 0.66-0.88 respectively). Cardiovascular, liver and renal system dysfunction were more frequently independently associated with mortality. General-ICU models had better performance in cirrhotic populations compared with CTP score; OSF and SOFA had the best predictive ability. Further prospective and validation studies are needed.

Relativistically strong electromagnetic radiation in a plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bulanov, S. V., E-mail: svbulanov@gmail.com, E-mail: bulanov.sergei@jaea.go.jp; Esirkepov, T. Zh.; Kando, M.

Physical processes in a plasma under the action of relativistically strong electromagnetic waves generated by high-power lasers have been briefly reviewed. These processes are of interest in view of the development of new methods for acceleration of charged particles, creation of sources of bright hard electromagnetic radiation, and investigation of macroscopic quantum-electrodynamical processes. Attention is focused on nonlinear waves in a laser plasma for the creation of compact electron accelerators. The acceleration of plasma bunches by the radiation pressure of light is the most efficient regime of ion acceleration. Coherent hard electromagnetic radiation in the relativistic plasma is generated inmore » the form of higher harmonics and/or electromagnetic pulses, which are compressed and intensified after reflection from relativistic mirrors created by nonlinear waves. In the limit of extremely strong electromagnetic waves, radiation friction, which accompanies the conversion of radiation from the optical range to the gamma range, fundamentally changes the behavior of the plasma. This process is accompanied by the production of electron–positron pairs, which is described within quantum electrodynamics theory.« less

Apparatus and method for enhanced chemical processing in high pressure and atmospheric plasmas produced by high frequency electromagnetic waves

DOEpatents

Efthimion, Philip C.; Helfritch, Dennis J.

1989-11-28

An apparatus and method for creating high temperature plasmas for enhanced chemical processing of gaseous fluids, toxic chemicals, and the like, at a wide range of pressures, especially at atmospheric and high pressures includes an electro-magnetic resonator cavity, preferably a reentrant cavity, and a wave guiding structure which connects an electro-magnetic source to the cavity. The cavity includes an intake port and an exhaust port, each having apertures in the conductive walls of the cavity sufficient for the intake of the gaseous fluids and for the discharge of the processed gaseous fluids. The apertures are sufficiently small to prevent the leakage of the electro-magnetic radiation from the cavity. Gaseous fluid flowing from the direction of the electro-magnetic source through the guiding wave structure and into the cavity acts on the plasma to push it away from the guiding wave structure and the electro-magnetic source. The gaseous fluid flow confines the high temperature plasma inside the cavity and allows complete chemical processing of the gaseous fluids at a wide range of pressures.

Manufacturing of hybrid aluminum copper joints by electromagnetic pulse welding - Identification of quantitative process windows

NASA Astrophysics Data System (ADS)

Psyk, Verena; Scheffler, Christian; Linnemann, Maik; Landgrebe, Dirk

2017-10-01

Compared to conventional joining techniques, electromagnetic pulse welding offers important advantages especially when it comes to dissimilar material connections as e.g. copper aluminum welds. However, due to missing guidelines and tools for process design, the process has not been widely implemented in industrial production, yet. In order to contribute to overcoming this obstacle, a combined numerical and experimental process analysis for electromagnetic pulse welding of Cu-DHP and EN AW-1050 was carried out and the results were consolidated in a quantitative collision parameter based process window.

Investigation on physiological and clinical effects of different light sources in TMJ photobiomodulation therapy

NASA Astrophysics Data System (ADS)

Kamenoff, J.

2017-02-01

Introduction Laser light Electromagnetic energy has some typical properties for discussions on laser irradiation abilities to control the acute and chronic disorders in TMJ. Material and Methods During the last six years we have been completed well controlled clinical trials based on the criteria of the American Academy of orofacial pain. The study over the 600 patients (300 women and 300 men), mean age of 47 years have been developed. Patients have been selected on the main clinical sign of TMJ pain and have been divided into four main groups according to the type of PDT method. Based on the action spectra, various wavelengths have been used for TMJ Photodynamic Therapy. Constant dose and time of exposition, as well as various range of frequencies have been applied. In this way the Laser biostimulation response has been directly proportional to the total energy dose, depending of light intensity. Physiological and clinical effects of the followed "active regions"- 660 - 680, 760 - 780, 810 - 830 and 904 - 987 nm have been valued by method of comparative analysis. Methods applied: LLLT - TENS - red surface laser acupuncture (LA), PIPBM - LA, Laser bioenergetics approach, Complex therapeutic program (CTP). Results evaluation will be demonstrated by comparative digital ortopantomograph analysis, EEG brain maps, VAS, a metric analysis of the level of the maximum active Mandible opening and EPST through electrophysiological signal evaluation of the patient's body.

Evaluation of the Bangalore Project.

ERIC Educational Resources Information Center

Beretta, Alan; Davies, Alan

1985-01-01

Follows up an article by Brumfit on the Bangalore/Madras Communicational Teaching Project (CTP). Discusses the framework, tests, and results of a 1984 evaluation supporting the claim that grammar construction can take place through a focus on meaning alone. (SED)

Direct detection of ligand binding to Sepharose-immobilised protein using saturation transfer double difference (STDD) NMR spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haselhorst, Thomas; Muenster-Kuehnel, Anja K.; Oschlies, Melanie

2007-08-10

We report an easy and direct application of 'Saturation Transfer Double Difference' (STDD) NMR spectroscopy to identify ligands that bind to a Sepharose-immobilised target protein. The model protein, cytidine 5'-monophosphate sialic acid (CMP-Sia) synthetase, was expressed as a Strep-Tag II fusion protein and immobilised on Strep-Tactin Sepharose. STD NMR experiments of the protein-enriched Sepharose matrix in the presence of a binding ligand (cytidine 5'-triphosphate, CTP) and a non-binding ligand ({alpha}/{beta}-glucose) clearly show that CTP binds to the immobilised enzyme, whereas glucose has no affinity. This approach has three major advantages: (a) only low quantities of protein are required, (b) nomore » specialised NMR technology or the application of additional data analysis by non-routine methods is required, and (c) easy multiple use of the immobilised protein is available.« less

Systematic design for trait introgression projects.

PubMed

Cameron, John N; Han, Ye; Wang, Lizhi; Beavis, William D

2017-10-01

Using an Operations Research approach, we demonstrate design of optimal trait introgression projects with respect to competing objectives. We demonstrate an innovative approach for designing Trait Introgression (TI) projects based on optimization principles from Operations Research. If the designs of TI projects are based on clear and measurable objectives, they can be translated into mathematical models with decision variables and constraints that can be translated into Pareto optimality plots associated with any arbitrary selection strategy. The Pareto plots can be used to make rational decisions concerning the trade-offs between maximizing the probability of success while minimizing costs and time. The systematic rigor associated with a cost, time and probability of success (CTP) framework is well suited to designing TI projects that require dynamic decision making. The CTP framework also revealed that previously identified 'best' strategies can be improved to be at least twice as effective without increasing time or expenses.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marengo, Barbara; Bottini, Consuelo; La Porta, C.A.M.

Phosphatidylethanolamine N-methyltransferase (PEMT) is the enzyme that converts phosphatidylethanolamine (PE) into phosphatidylcholine. We have previously shown that PEMT suppressed hepatoma growth by triggering apoptosis. We investigate whether PEMT controlled cell death and cell proliferation triggered by fasting/refeeding and whether it is a marker of early preneoplastic lesions. The induction of programmed cell death and suppression of cell proliferation by fasting were associated with enhanced PEMT expression and activity, and with a decrease in CTP:phosphocholine cytidylyltransferase expression. Refeeding returned the liver growth and expression of CTP:phosphocholine cytidylyltransferase to control levels, while the expression of PEMT decreased to below control values. Aftermore » DENA administration, PEMT protein, evaluated by Western blotting, slightly increased, but it remained below control levels. The treatment with 20 mg/kg DENA to refed rats induced the appearance of initiated hepatocytes that were negative for PEMT expression. Present findings indicate that PEMT is a novel tumour marker for early liver preneoplastic lesions.« less

Single and Multi-Pulse Low-Energy Conical Theta Pinch Inductive Pulsed Plasma Thruster Performance

NASA Technical Reports Server (NTRS)

Hallock, Ashley K.; Martin, Adam; Polzin, Kurt; Kimberlin, Adam; Eskridge, Richard

2013-01-01

Fabricated and tested CTP IPPTs at cone angles of 20deg, 38deg, and 60deg, and performed direct single-pulse impulse bit measurements with continuous gas flow. Single pulse performance highest for 38deg angle with impulse bit of approx.1 mN-s for both argon and xenon. Estimated efficiencies low, but not unexpectedly so based on historical data trends and the direction of the force vector in the CTP. Capacitor charging system assembled to provide rapid recharging of capacitor bank, permitting repetition-rate operation. IPPT operated at repetition-rate of 5 Hz, at maximum average power of 2.5 kW, representing to our knowledge the highest average power for a repetitively-pulsed thruster. Average thrust in repetition-rate mode (at 5 kV, 75 sccm argon) was greater than simply multiplying the single-pulse impulse bit and the repetition rate.

Electromagnetic Radiation Disturbed the Photosynthesis of Microcystis aeruginosa at the Proteomics Level.

PubMed

Tang, Chao; Yang, Chuanjun; Yu, Hui; Tian, Shen; Huang, Xiaomei; Wang, Weiyi; Cai, Peng

2018-01-11

Photosynthesis of Microcystis aeruginosa under Electromagnetic Radiation (1.8 GHz, 40 V/m) was studied by using the proteomics. A total of 30 differentially expressed proteins, including 15 up-regulated and 15 down-regulated proteins, were obtained in this study. The differentially expressed proteins were significantly enriched in the photosynthesis pathway, in which the protein expression levels of photosystems II cytochrome b559 α subunit, cytochrome C550, PsbY, and F-type ATP synthase (a, b) decreased. Our results indicated that electromagnetic radiation altered the photosynthesis-related protein expression levels, and aimed at the function of photosynthetic pigments, photosystems II potential activity, photosynthetic electron transport process, and photosynthetic phosphorylation process of M. aeruginosa. Based on the above evidence, that photoreaction system may be deduced as a target of electromagnetic radiation on the photosynthesis in cyanobacteria; the photoreaction system of cyanobacteria is a hypothetical "shared target effector" that responds to light and electromagnetic radiation; moreover, electromagnetic radiation does not act on the functional proteins themselves but their expression processes.

Conversion of electromagnetic energy in Z-pinch process of single planar wire arrays at 1.5 MA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liangping, Wang; Mo, Li; Juanjuan, Han

The electromagnetic energy conversion in the Z-pinch process of single planar wire arrays was studied on Qiangguang generator (1.5 MA, 100 ns). Electrical diagnostics were established to monitor the voltage of the cathode-anode gap and the load current for calculating the electromagnetic energy. Lumped-element circuit model of wire arrays was employed to analyze the electromagnetic energy conversion. Inductance as well as resistance of a wire array during the Z-pinch process was also investigated. Experimental data indicate that the electromagnetic energy is mainly converted to magnetic energy and kinetic energy and ohmic heating energy can be neglected before the final stagnation. Themore » kinetic energy can be responsible for the x-ray radiation before the peak power. After the stagnation, the electromagnetic energy coupled by the load continues increasing and the resistance of the load achieves its maximum of 0.6–1.0 Ω in about 10–20 ns.« less

SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia.

PubMed

Schneider, Constanze; Oellerich, Thomas; Baldauf, Hanna-Mari; Schwarz, Sarah-Marie; Thomas, Dominique; Flick, Robert; Bohnenberger, Hanibal; Kaderali, Lars; Stegmann, Lena; Cremer, Anjali; Martin, Margarethe; Lohmeyer, Julian; Michaelis, Martin; Hornung, Veit; Schliemann, Christoph; Berdel, Wolfgang E; Hartmann, Wolfgang; Wardelmann, Eva; Comoglio, Federico; Hansmann, Martin-Leo; Yakunin, Alexander F; Geisslinger, Gerd; Ströbel, Philipp; Ferreirós, Nerea; Serve, Hubert; Keppler, Oliver T; Cinatl, Jindrich

2017-02-01

The nucleoside analog cytarabine (Ara-C) is an essential component of primary and salvage chemotherapy regimens for acute myeloid leukemia (AML). After cellular uptake, Ara-C is converted into its therapeutically active triphosphate metabolite, Ara-CTP, which exerts antileukemic effects, primarily by inhibiting DNA synthesis in proliferating cells. Currently, a substantial fraction of patients with AML fail to respond effectively to Ara-C therapy, and reliable biomarkers for predicting the therapeutic response to Ara-C are lacking. SAMHD1 is a deoxynucleoside triphosphate (dNTP) triphosphohydrolase that cleaves physiological dNTPs into deoxyribonucleosides and inorganic triphosphate. Although it has been postulated that SAMHD1 sensitizes cancer cells to nucleoside-analog derivatives through the depletion of competing dNTPs, we show here that SAMHD1 reduces Ara-C cytotoxicity in AML cells. Mechanistically, dGTP-activated SAMHD1 hydrolyzes Ara-CTP, which results in a drastic reduction of Ara-CTP in leukemic cells. Loss of SAMHD1 activity-through genetic depletion, mutational inactivation of its triphosphohydrolase activity or proteasomal degradation using specialized, virus-like particles-potentiates the cytotoxicity of Ara-C in AML cells. In mouse models of retroviral AML transplantation, as well as in retrospective analyses of adult patients with AML, the response to Ara-C-containing therapy was inversely correlated with SAMHD1 expression. These results identify SAMHD1 as a potential biomarker for the stratification of patients with AML who might best respond to Ara-C-based therapy and as a target for treating Ara-C-refractory AML.

Central Equatorial Pacific Sea Surface Temperatures During the Last Glacial Maximum

NASA Astrophysics Data System (ADS)

Monteagudo, M. M.; Lynch-Stieglitz, J.; Schmidt, M. W.

2017-12-01

The state of the tropical Pacific ocean-atmosphere system during the Last Glacial Maximum (LGM, 19,000-23,000 years BP) remains an area of uncertainty. Spatial patterns of tropical Pacific sea surface temperature (SST) offer insight into atmospheric circulation (i.e. Walker Circulation), however, few records exist for the Central Tropical Pacific (CTP). The few existing glacial CTP SST reconstructions indicate 1-2 °C of warming based on foraminiferal transfer functions (CLIMAP Project Members, 1976). In contrast, evidence from geochemical proxies (Mg/Ca, UK'37, TEX86) show 1-3.5 °C cooling in the eastern and western tropical Pacific (e.g. MARGO Project Members, 2009). In this study we present the first Mg/Ca estimates of glacial CTP SST from a meridional sediment core transect along the Line Islands Ridge (0-7°N, 156-162 °W). We use a time slice approach to establish the magnitude of glacial-interglacial SST change between the LGM (19,000-23,0000 years BP) and the Holocene (0-10,000 years BP) using Mg/Ca in the surface-dwelling foraminifera Globigerinoides ruber. Our results indicate cooling at all latitudes, ranging between 1.2-2.7 °C (Holocene-LGM SST). Northern cores (6.83-2.77 °N) exhibit a smaller glacial-interglacial SST difference than equatorial site 20BB at 1.27 °N. The data generated thus far suggest the glacial meridional SST gradient may have been steeper, possibly as a result of increased zonal winds, equatorial upwelling, or westward expansion of the Eastern Pacific Cold Tongue.

[Etiology and complications of liver cirrhosis: data from a German centre].

PubMed

Sivanathan, V; Kittner, J M; Sprinzl, M F; Weinmann, A; Koch, S; Wiltink, J; Nguyen-Tat, M; Marquardt, J U; Wörns, M A; Zimmermann, T; Lang, H; Galle, P R; Schattenberg, J M

2014-09-01

Liver cirrhosis develops as a terminal complication of chronic liver disease. The clinical course is determined by the underlying etiology and the accompanying risk factors, which are influenced by the geographic and cultural background. A total of 236 patients (159 men, 77 women, median age 57 [22-81] years) were included for retrospective analysis between July 2012 and February 2014 using standardized questionnaires during an outpatient visit at a hepatology clinic. The most common etiologies of liver cirrhosis were related to alcohol consumption (52 %), chronic hepatitis C (28 %) or hepatitis B (14 %) infection and NASH (nonalcoholic steatohepatitis, 6 %). At the time of presentation 55 % patients had compensated cirrhosis corresponding to Child-Turcotte-Pugh (CTP) stage A, while 45 % were in a decompensated stage (30 % CTP B and 15 % CTP C). Subgroups were analyzed for the incidence of complications and the emergence of infections. Most frequently esophageal varices (60 %) and ascites (49 %) were observed, followed by pleural effusion (14 %), hepatic encephalopathy (25 %) or hepatorenal syndrome (18 %). 16 % of patients exhibited infection based on clinical criteria. An infective agent was isolated in 38 % of all cases with infection and of those 50 % were gram positive bacteria. In multivariate analysis only the presence of ascites was an independent risk factor for infection. Despite improved medical therapies for viral hepatitis, these were the most frequent causes of liver cirrhosis, closely followed by alcoholic cirrhosis. The observed complications included bacterial infection and complication related to portal hypertension. © Georg Thieme Verlag KG Stuttgart · New York.

SU-G-IeP2-06: Evaluation of Registration Accuracy for Cone-Beam CT Reconstruction Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, J; Wang, P; Zhang, H

2016-06-15

Purpose: Cone-beam (CB) computed tomography (CT) is used for image guidance during radiotherapy treatment delivery. Conventional Feldkamp and compressed sensing (CS) based CBCT recon-struction techniques are compared for image registration. This study is to evaluate the image registration accuracy of conventional and CS CBCT for head-and-neck (HN) patients. Methods: Ten HN patients with oropharyngeal tumors were retrospectively selected. Each HN patient had one planning CT (CTP) and three CBCTs were acquired during an adaptive radiotherapy proto-col. Each CBCT was reconstructed by both the conventional (CBCTCON) and compressed sens-ing (CBCTCS) methods. Two oncologists manually labeled 23 landmarks of normal tissue andmore » implanted gold markers on both the CTP and CBCTCON. Subsequently, landmarks on CTp were propagated to CBCTs, using a b-spline-based deformable image registration (DIR) and rigid registration (RR). The errors of these registration methods between two CBCT methods were calcu-lated. Results: For DIR, the mean distance between the propagated and the labeled landmarks was 2.8 mm ± 0.52 for CBCTCS, and 3.5 mm ± 0.75 for CBCTCON. For RR, the mean distance between the propagated and the labeled landmarks was 6.8 mm ± 0.92 for CBCTCS, and 8.7 mm ± 0.95 CBCTCON. Conclusion: This study has demonstrated that CS CBCT is more accurate than conventional CBCT in image registration by both rigid and non-rigid methods. It is potentially suggested that CS CBCT is an improved image modality for image guided adaptive applications.« less

Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease.

PubMed

Li, Jin-Ping; Zhao, De-Li; Jiang, Hui-Jie; Huang, Ya-Hua; Li, Da-Qing; Wan, Yong; Liu, Xin-Ding; Wang, Jin-E

2011-02-01

Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhotic liver disease by this fast imaging method. CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The value of HBF at the tumor rim was significantly higher than that in the controls. HBF, HBV, HAI, HAP and HPP, but not MTT and PS, were significantly higher in the cirrhotic liver parenchyma involved with HCC than those of the controls. Perfusion parameters were not significantly different between the controls and the cirrhotic liver parenchyma not involved with HCC. CTP can clearly distinguish tumor from cirrhotic liver parenchyma and controls and can provide quantitative information about tumor-related angiogenesis, which can be used to assess tumor vascularization in cirrhotic liver disease.

Design, construction, test and field support of a containerless payload package for rocket flight. [electromagnetic heating and confinement

NASA Technical Reports Server (NTRS)

1977-01-01

The performance of a device for electromagnetically heating and positioning containerless melts during space processing was evaluated during a 360 second 0-g suborbital sounding rocket flight. Components of the electromagnetic containerless processing package (ECPP), its operation, and interface with the rocket are described along with flight and qualification tests results.

Spectrum Management and Electromagnetic Environmental Effects (E3) Business Process

DTIC Science & Technology

2010-05-06

HAZARDS OF ELECTROMAGNETIC RADIATION TO ORDNANCE ( HERO ) SURVEY. XM11: IS THERE A CURRENT ELECTROMAGNETIC INTERFERENCE (EMI) SITE SURVEY. SM & EMI Navy...PERSONNEL (HERP) / FUEL (HERF) SURVEY. XM10: IS THERE A CURRENT HAZARDS OF ELECTROMAGNETIC RADIATION TO ORDNANCE ( HERO ) SURVEY. XM11...OF ALL KNOWN ELECTROMAGNETIC INTERFERENCE (EMI) FIXES INSTALLED ONE YEAR AFTER SURVEY COMPLETION. M05: OF ALL RADIATION HAZARDS

Electromagnetic disturbance of electric drive system signal is extracted based on PLS

NASA Astrophysics Data System (ADS)

Wang, Yun; Wang, Chuanqi; Yang, Weidong; Zhang, Xu; Jiang, Li; Hou, Shuai; Chen, Xichen

2018-05-01

At present ISO11452 and GB/T33014 specified by electromagnetic immunity are narrowband electromagnetic radiation, but our exposure to electromagnetic radiation at ordinary times is not only a narrowband electromagnetic radiation, and some broadband electromagnetic radiation, and even some of the more complex electromagnetic environment. In terms of Electric vehicles, electric drive system is a kind of complex electromagnetic disturbance source, is not only a narrow-band signal, there are a lot of broadband signal, this paper puts forward PLS data processing method is adopted to analyze the electric drive system of electromagnetic disturbance, this kind of method to extract the data can be provide reliable data support for future standards.

Reemission spectra and inelastic processes at interaction of attosecond and shorter duration electromagnetic pulses with atoms

NASA Astrophysics Data System (ADS)

Makarov, D. N.; Matveev, V. I.

2017-01-01

Inelastic processes and the reemission of attosecond and shorter electromagnetic pulses by atoms have been considered within the analytical solution of the Schrödinger equation in the sudden perturbation approximation. A method of calculations with the exact inclusion of spatial inhomogeneity of the field of an ultrashort pulse and the momenta of photons in the reemission processes has been developed. The probabilities of inelastic processes and spectra of reemission of ultrashort electromagnetic pulses by one- and many-electron atoms have been calculated. The results have been presented in the form of analytical formulas.

On electromagnetic forming processes in finitely strained solids: Theory and examples

NASA Astrophysics Data System (ADS)

Thomas, J. D.; Triantafyllidis, N.

2009-08-01

The process of electromagnetic forming (EMF) is a high velocity manufacturing technique that uses electromagnetic (Lorentz) body forces to shape sheet metal parts. EMF holds several advantages over conventional forming techniques: speed, repeatability, one-sided tooling, and most importantly considerable ductility increase in several metals. Current modeling techniques for EMF processes are not based on coupled variational principles to simultaneously account for electromagnetic and mechanical effects. Typically, separate solutions to the electromagnetic (Maxwell) and motion (Newton) equations are combined in staggered or lock-step methods, sequentially solving the mechanical and electromagnetic problems. The present work addresses these issues by introducing a fully coupled Lagrangian (reference configuration) least-action variational principle, involving magnetic flux and electric potentials and the displacement field as independent variables. The corresponding Euler-Lagrange equations are Maxwell's and Newton's equations in the reference configuration, which are shown to coincide with their current configuration counterparts obtained independently by a direct approach. The general theory is subsequently simplified for EMF processes by considering the eddy current approximation. Next, an application is presented for axisymmetric EMF problems. It is shown that the proposed variational principle forms the basis of a variational integration numerical scheme that provides an efficient staggered solution algorithm. As an illustration a number of such processes are simulated, inspired by recent experiments of freely expanding uncoated and polyurea-coated aluminum tubes.

Cooperation, Technology, and Performance: A Case Study.

ERIC Educational Resources Information Center

Cavanagh, Thomas; Dickenson, Sabrina; Brandt, Suzanne

1999-01-01

Describes the CTP (Cooperation, Technology, and Performance) model and explains how it is used by the Department of Veterans Affairs-Veteran's Benefit Administration (VBA) for training. Discusses task analysis; computer-based training; cooperative-based learning environments; technology-based learning; performance-assessment methods; courseware…

10 CFR Appendix H to Part 110 - Illustrative List of Electromagnetic Enrichment Plant Equipment and Components Under NRC Export...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Illustrative List of Electromagnetic Enrichment Plant... Appendix H to Part 110—Illustrative List of Electromagnetic Enrichment Plant Equipment and Components Under NRC Export Licensing Authority Note—In the electromagnetic process, uranium metal ions produced by...

10 CFR Appendix H to Part 110 - Illustrative List of Electromagnetic Enrichment Plant Equipment and Components Under NRC Export...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Illustrative List of Electromagnetic Enrichment Plant... Appendix H to Part 110—Illustrative List of Electromagnetic Enrichment Plant Equipment and Components Under NRC Export Licensing Authority Note—In the electromagnetic process, uranium metal ions produced by...

10 CFR Appendix H to Part 110 - Illustrative List of Electromagnetic Enrichment Plant Equipment and Components Under NRC Export...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Illustrative List of Electromagnetic Enrichment Plant... Appendix H to Part 110—Illustrative List of Electromagnetic Enrichment Plant Equipment and Components Under NRC Export Licensing Authority Note—In the electromagnetic process, uranium metal ions produced by...

10 CFR Appendix H to Part 110 - Illustrative List of Electromagnetic Enrichment Plant Equipment and Components Under NRC Export...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Illustrative List of Electromagnetic Enrichment Plant... Appendix H to Part 110—Illustrative List of Electromagnetic Enrichment Plant Equipment and Components Under NRC Export Licensing Authority Note—In the electromagnetic process, uranium metal ions produced by...

10 CFR Appendix H to Part 110 - Illustrative List of Electromagnetic Enrichment Plant Equipment and Components Under NRC Export...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Illustrative List of Electromagnetic Enrichment Plant... Appendix H to Part 110—Illustrative List of Electromagnetic Enrichment Plant Equipment and Components Under NRC Export Licensing Authority Note: In the electromagnetic process, uranium metal ions produced by...

Effects of low-intensity ultrahigh frequency electromagnetic radiation on inflammatory processes.

PubMed

Lushnikov, K V; Shumilina, Yu V; Yakushina, V S; Gapeev, A B; Sadovnikov, V B; Chemeris, N K

2004-04-01

Low-intensity ultrahigh frequency electromagnetic radiation (42 GHz, 100 microW/cm(2)) reduces the severity of inflammation and inhibits production of active oxygen forms by inflammatory exudate neutrophils only in mice with inflammatory process. These data suggest that some therapeutic effects of electromagnetic radiation can be explained by its antiinflammatory effect which is realized via modulation of functional activity of neutrophils in the focus of inflammation.

Numerical simulation of electromagnetic surface treatment

NASA Astrophysics Data System (ADS)

Sonde, Emmanuel; Chaise, Thibaut; Nelias, Daniel; Robin, Vincent

2018-01-01

Surface treatment methods, such as shot peening or laser shock peening, are generally used to introduce superficial compressive residual stresses in mechanical parts. These processes are carried out during the manufacturing steps or for the purpose of repairing. The compressive residual stresses prevent the initiation and growth of cracks and thus improve the fatigue life of mechanical components. Electromagnetic pulse peening (EMP) is an innovative process that could be used to introduce compressive residual stresses in conductive materials. It acts by generating a high transient electromagnetic field near the working surface. In this paper, the EMP process is presented and a sequentially coupled electromagnetic and mechanical model is developed for its simulation. This 2D axisymmetric model is set up with the commercial finite element software SYSWELD. After description and validation, the numerical model is used to simulate a case of introducing residual stresses of compression in a nickel-based alloy 690 thick sample, by the means of electromagnetic pulses. The results are presented in terms of effective plastic strain and residual mean stress. The influence of the process parameters, such as current intensity and frequency, on the results is analyzed. Finally, the predictability of the process is shown by several correlation studies.

Internal Carotid Artery Stenosis and Collateral Recruitment in Stroke Patients.

PubMed

Dankbaar, Jan W; Kerckhoffs, Kelly G P; Horsch, Alexander D; van der Schaaf, Irene C; Kappelle, L Jaap; Velthuis, Birgitta K

2017-04-24

Leptomeningeal collaterals improve outcome in stroke patients. There is great individual variability in their extent. Internal carotid artery (ICA) stenosis may lead to more extensive recruitment of leptomeningeal collaterals. The purpose of this study was to evaluate the association of pre-existing ICA stenosis with leptomeningeal collateral filling visualized with computed tomography perfusion (CTP). From a prospective acute ischemic stroke cohort, patients were included with an M1 middle cerebral artery (MCA) occlusion and absent ipsilateral, extracranial ICA occlusion. ICA stenosis was determined on admission CT angiography (CTA). Leptomeningeal collaterals were graded as good (>50%) or poor (≤50%) collateral filling in the affected MCA territory on CTP-derived vessel images of the admission scan. The association between ipsilateral ICA stenosis ≥70% and extent of collateral filling was analyzed using logistic regression. In a multivariable analysis the odds ratio (OR) of ICA stenosis ≥70% was adjusted for complete circle of Willis, gender and age. We included 188 patients in our analyses, 50 (26.6%) patients were classified as having poor collateral filling and 138 (73.4%) as good. Of the patients 4 with poor collateral filling had an ICA stenosis ≥70% and 14 with good collateral filling. Unadjusted and adjusted ORs of ICA stenosis ≥70% for good collateral filling were 1.30 (0.41-4.15) and 2.67 (0.81-8.77), respectively. Patients with poor collateral filling had a significantly worse outcome (90-day modified Rankin scale 3-6; 80% versus 52%, p = 0.001). No association was found between pre-existing ICA stenosis and extent of CTP derived collateral filling in patients with an M1 occlusion.

Kinetic analysis of bypass of abasic site by the catalytic core of yeast DNA polymerase eta.

PubMed

Yang, Juntang; Wang, Rong; Liu, Binyan; Xue, Qizhen; Zhong, Mengyu; Zeng, Hao; Zhang, Huidong

2015-09-01

Abasic sites (Apurinic/apyrimidinic (AP) sites), produced ∼ 50,000 times/cell/day, are very blocking and miscoding. To better understand miscoding mechanisms of abasic site for yeast DNA polymerase η, pre-steady-state nucleotide incorporation and LC-MS/MS sequence analysis of extension product were studied using pol η(core) (catalytic core, residues 1-513), which can completely eliminate the potential effects of the C-terminal C2H2 motif of pol η on dNTP incorporation. The extension beyond the abasic site was very inefficient. Compared with incorporation of dCTP opposite G, the incorporation efficiencies opposite abasic site were greatly reduced according to the order of dGTP > dATP > dCTP and dTTP. Pol η(core) showed no fast burst phase for any incorporation opposite G or abasic site, suggesting that the catalytic step is not faster than the dissociation of polymerase from DNA. LC-MS/MS sequence analysis of extension products showed that 53% products were dGTP misincorporation, 33% were dATP and 14% were -1 frameshift, indicating that Pol η(core) bypasses abasic site by a combined G-rule, A-rule and -1 frameshift deletions. Compared with full-length pol η, pol η(core) relatively reduced the efficiency of incorporation of dCTP opposite G, increased the efficiencies of dNTP incorporation opposite abasic site and the exclusive incorporation of dGTP opposite abasic site, but inhibited the extension beyond abasic site, and increased the priority in extension of A: abasic site relative to G: abasic site. This study provides further understanding in the mutation mechanism of abasic sites for yeast DNA polymerase η. Copyright © 2015 Elsevier B.V. All rights reserved.

Hypotonic activation of short ClC3 isoform is modulated by direct interaction between its cytosolic C-terminal tail and subcortical actin filaments.

PubMed

McCloskey, Diana T; Doherty, Lynda; Dai, Yan-Ping; Miller, Lisa; Hume, Joseph R; Yamboliev, Ilia A

2007-06-08

Short ClC3 isoform (sClC3) functions as a volume-sensitive outwardly rectifying anion channel (VSOAC) in some cell types. In previous studies, we have shown that the hypotonic activation of sClC3 is linked to cell swelling-mediated remodeling of the actin cytoskeleton. In the present study, we have tested the hypothesis that the cytosolic tails of sClC3 bind to actin directly and that binding modulates the hypotonic activation of the channel. Co-sedimentation assays in vitro demonstrated a strong binding between the glutathione S-transferase-fused cytosolic C terminus of sClC3 (GST-sClC3-CT) to filamentous actin (F-actin) but not to globular monomeric actin (G-actin). The GST-fused N terminus (GST-sClC3-NT) exhibited low binding affinity to both G- and F-actin. Co-sedimentation experiments with progressively truncated GST-sClC3-CT indicated that the F-actin binding region is located between amino acids 690 and 760 of sClC3. Two synthetic peptides mapping basic clusters of the cytosolic sClC3-CT (CTP2, isoleucine 716 to leucine 734; and CTP3, proline 688 to proline 709) prevented binding of GST-sClC3-CT to F-actin in vitro. Dialysis into NIH/3T3 cells of these two peptides (but not of synthetic peptide CTP1 (isoleucine 737 to glutamine 748)) reduced the maximal current density by 60 and 38%, respectively. Based on these results, we have concluded that, by direct interaction with subcortical actin filaments, sClC3 contributes to the hypotonic stress-induced VSOACs in NIH/3T3 cells.

How a low-fidelity DNA polymerase chooses non-Watson-Crick from Watson-Crick incorporation.

PubMed

Wu, Wen-Jin; Su, Mei-I; Wu, Jian-Li; Kumar, Sandeep; Lim, Liang-Hin; Wang, Chun-Wei Eric; Nelissen, Frank H T; Chen, Ming-Chuan Chad; Doreleijers, Jurgen F; Wijmenga, Sybren S; Tsai, Ming-Daw

2014-04-02

A dogma for DNA polymerase catalysis is that the enzyme binds DNA first, followed by MgdNTP. This mechanism contributes to the selection of correct dNTP by Watson-Crick base pairing, but it cannot explain how low-fidelity DNA polymerases overcome Watson-Crick base pairing to catalyze non-Watson-Crick dNTP incorporation. DNA polymerase X from the deadly African swine fever virus (Pol X) is a half-sized repair polymerase that catalyzes efficient dG:dGTP incorporation in addition to correct repair. Here we report the use of solution structures of Pol X in the free, binary (Pol X:MgdGTP), and ternary (Pol X:DNA:MgdGTP with dG:dGTP non-Watson-Crick pairing) forms, along with functional analyses, to show that Pol X uses multiple unprecedented strategies to achieve the mutagenic dG:dGTP incorporation. Unlike high fidelity polymerases, Pol X can prebind purine MgdNTP tightly and undergo a specific conformational change in the absence of DNA. The prebound MgdGTP assumes an unusual syn conformation stabilized by partial ring stacking with His115. Upon binding of a gapped DNA, also with a unique mechanism involving primarily helix αE, the prebound syn-dGTP forms a Hoogsteen base pair with the template anti-dG. Interestingly, while Pol X prebinds MgdCTP weakly, the correct dG:dCTP ternary complex is readily formed in the presence of DNA. H115A mutation disrupted MgdGTP binding and dG:dGTP ternary complex formation but not dG:dCTP ternary complex formation. The results demonstrate the first solution structural view of DNA polymerase catalysis, a unique DNA binding mode, and a novel mechanism for non-Watson-Crick incorporation by a low-fidelity DNA polymerase.

Critical elements in the development of cell therapy potency assays for ischemic conditions.

PubMed

Porat, Yael; Abraham, Eytan; Karnieli, Ohad; Nahum, Sagi; Woda, Juliana; Zylberberg, Claudia

2015-07-01

A successful potency assay for a cell therapy product (CTP) used in the treatment of ischemic conditions should quantitatively measure relevant biological properties that predict therapeutic activity. This is especially challenging because of numerous degrees of complexity stemming from factors that include a multifactorial complex mechanism of action, cell source, inherent cell characteristics, culture method, administration mode and the in vivo conditions to which the cells are exposed. The expected biological function of a CTP encompasses complex interactions that range from a biochemical, metabolic or immunological activity to structural replacement of damaged tissue or organ. Therefore, the requirements for full characterization of the active substance with respect to biological function could be taxing. Moreover, the specific mechanism of action is often difficult to pinpoint to a specific molecular entity; rather, it is more dependent on the functionality of the cellular components acting in a in a multifactorial fashion. In the case of ischemic conditions, the cell therapy mechanism of action can vary from angiogenesis, vasculogenesis and arteriogenesis that may activate different pathways and clinical outcomes. The CTP cellular attributes with relation to the suggested mechanism of action can be used for the development of quantitative and reproducible analytical potency assays. CTPs selected and released on the basis of such potency assays should have the highest probability of providing meaningful clinical benefit for patients. This White Paper will discuss and give examples for key elements in the development of a potency assay for treatment of ischemic disorders treated by the use of CTPs. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

An auto-inhibitory helix in CTP:phosphocholine cytidylyltransferase hijacks the catalytic residue and constrains a pliable, domain-bridging helix pair

PubMed Central

Ramezanpour, Mohsen; Lee, Jaeyong; Taneva, Svetla G.; Tieleman, D. Peter; Cornell, Rosemary B.

2018-01-01

The activity of CTP:phosphocholine cytidylyltransferase (CCT), a key enzyme in phosphatidylcholine synthesis, is regulated by reversible interactions of a lipid-inducible amphipathic helix (domain M) with membrane phospholipids. When dissociated from membranes, a portion of the M domain functions as an auto-inhibitory (AI) element to suppress catalysis. The AI helix from each subunit binds to a pair of α helices (αE) that extend from the base of the catalytic dimer to create a four-helix bundle. The bound AI helices make intimate contact with loop L2, housing a key catalytic residue, Lys122. The impacts of the AI helix on active-site dynamics and positioning of Lys122 are unknown. Extensive MD simulations with and without the AI helix revealed that backbone carbonyl oxygens at the point of contact between the AI helix and loop L2 can entrap the Lys122 side chain, effectively competing with the substrate, CTP. In silico, removal of the AI helices dramatically increased αE dynamics at a predicted break in the middle of these helices, enabling them to splay apart and forge new contacts with loop L2. In vitro cross-linking confirmed the reorganization of the αE element upon membrane binding of the AI helix. Moreover, when αE bending was prevented by disulfide engineering, CCT activation by membrane binding was thwarted. These findings suggest a novel two-part auto-inhibitory mechanism for CCT involving capture of Lys122 and restraint of the pliable αE helices. We propose that membrane binding enables bending of the αE helices, bringing the active site closer to the membrane surface. PMID:29519816

Correlating Computed Tomography Perfusion Changes in the Pharyngeal Constrictor Muscles During Head-and-Neck Radiotherapy to Dysphagia Outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Truong, Minh Tam, E-mail: mitruong@bu.edu; Department of Radiology, Boston Medical Center and Boston University School of Medicine, Boston, MA; Lee, Richard

2012-02-01

Purpose: To measure changes in perfusion of the pharyngeal constrictor muscles (PCM) using CT perfusion (CTP) imaging during a course of definitive radiotherapy (RT) in head-and-neck cancer (HNC) patients and correlate with dysphagia outcome after RT. Methods and Materials: Fifteen HNC patients underwent CTP imaging of the PCM at baseline and Weeks 2, 4, and 6 during RT and 6 weeks after RT. Blood flow and blood volume were measured in the PCM, and percentage change from baseline scan was determined. A single physician-based assessment of dysphagia was performed every 3 months after RT using the Common Terminology Criteria formore » Adverse Events, version 3.0 grading system. Results: With a median follow-up of 28 months (range, 6-44 months), Grade 3 dysphagia was present in 7 of 15 patients, and 8 patients experienced Grade 0-2 dysphagia. The CTP parameters at Week 2 of RT demonstrated an increase in mean PCM blood flow of 161.9% vs. 12.3% (p = 0.007) and an increase in mean PCM blood volume of 96.6% vs. 8.7% (p = 0.039) in patients with 6-month post-RT Grade 3 dysphagia and Grade 0-2 dysphagia, respectively. On multivariate analysis, when adjusting for smoking history, tumor volume, and baseline dysphagia status, an increase in blood flow in the second week of RT was significant for 3- and 6-month Grade 3 dysphagia (p < 0.05). Conclusions: Perfusion changes in the PCM during Week 2 of RT in the PCM may predict the severity of dysphagia after HNC RT.« less

The ENSO Effects on Tropical Clouds and Top-of-Atmosphere Cloud Radiative Effects in CMIP5 Models

NASA Technical Reports Server (NTRS)

Su, Wenying; Wang, Hailan

2015-01-01

The El Nino-Southern Oscillation (ENSO) effects on tropical clouds and top-of-atmosphere (TOA) cloud radiative effects (CREs) in Coupled Model Intercomparison Project Phase5 (CMIP5) models are evaluated using satellite-based observations and International Satellite Cloud Climatology Project satellite simulator output. Climatologically, most CMIP5 models produce considerably less total cloud amount with higher cloud top and notably larger reflectivity than observations in tropical Indo-Pacific (60 degrees East - 200 degrees East; 10 degrees South - 10 degrees North). During ENSO, most CMIP5 models considerably underestimate TOA CRE and cloud changes over western tropical Pacific. Over central tropical Pacific, while the multi-model mean resembles observations in TOA CRE and cloud amount anomalies, it notably overestimates cloud top pressure (CTP) decreases; there are also substantial inter-model variations. The relative effects of changes in cloud properties, temperature and humidity on TOA CRE anomalies during ENSO in the CMIP5 models are assessed using cloud radiative kernels. The CMIP5 models agree with observations in that their TOA shortwave CRE anomalies are primarily contributed by total cloud amount changes, and their TOA longwave CRE anomalies are mostly contributed by changes in both total cloud amount and CTP. The model biases in TOA CRE anomalies particularly the strong underestimations over western tropical Pacific are, however, mainly explained by model biases in CTP and cloud optical thickness (tau) changes. Despite the distinct model cloud biases particularly in tau regime, the TOA CRE anomalies from cloud amount changes are comparable between the CMIP5 models and observations, because of the strong compensations between model underestimation of TOA CRE anomalies from thin clouds and overestimation from medium and thick clouds.

Nanostructuring effect of multi-walled carbon nanotubes on electrochemical properties of carbon foam as constructive electrode for lead acid battery

NASA Astrophysics Data System (ADS)

Kumar, Rajeev; Kumari, Saroj; Mathur, Rakesh B.; Dhakate, Sanjay R.

2015-01-01

In the present study, nanostructuring effect of multi-walled carbon nanotubes (MWCNTs) on electrochemical properties of coal tar pitch (CTP) based carbon foam (CFoam) was investigated. The different weight fractions of MWCNTs were mixed with CTP and foam was developed from the mixture of CTP and MWCNTs by sacrificial template technique and heat treated at 1,400 and 2,500 °C in inert atmosphere. These foams were characterized by scanning electron microscopy, X-ray diffraction, and potentiostat PARSTAT for cyclic voltammetry. It was observed that, bulk density of CFoam increases with increasing MWCNTs content and decreases after certain amount. The MWCNTs influence the morphology of CFoam and increase the width of ligaments as well as surface area. During the heat treatment, stresses exerting at MWCNTs/carbon interface accelerate ordering of the graphene layer which have positive effect on the electrochemical properties of CFoam. The current density increases from 475 to 675 mA/cm2 of 1,400 °C heat treated and 95 to 210 mA/cm2 of 2,500 °C heat-treated CFoam with 1 wt% MWCNTs. The specific capacitance was decreases with increasing the scan rate from 100 to 1,000 mV/s. In case of 1 % MWCNTs content CFoam the specific capacitance at the scan rate 100 mV/s was increased from 850 to 1,250 μF/cm2 and 48 to 340 μF/cm2 of CFoam heat treated at 1,400 °C and 2,500 °C respectively. Thus, the higher value surface area and current density of MWCNTs-incorporated CFoam heat treated to 1,400 °C can be suitable for lead acid battery electrode with improved charging capability.

Scale-up and large-scale production of Tetraselmis sp. CTP4 (Chlorophyta) for CO2 mitigation: from an agar plate to 100-m3 industrial photobioreactors.

PubMed

Pereira, Hugo; Páramo, Jaime; Silva, Joana; Marques, Ana; Barros, Ana; Maurício, Dinis; Santos, Tamára; Schulze, Peter; Barros, Raúl; Gouveia, Luísa; Barreira, Luísa; Varela, João

2018-03-23

Industrial production of novel microalgal isolates is key to improving the current portfolio of available strains that are able to grow in large-scale production systems for different biotechnological applications, including carbon mitigation. In this context, Tetraselmis sp. CTP4 was successfully scaled up from an agar plate to 35- and 100-m 3 industrial scale tubular photobioreactors (PBR). Growth was performed semi-continuously for 60 days in the autumn-winter season (17 th October - 14 th December). Optimisation of tubular PBR operations showed that improved productivities were obtained at a culture velocity of 0.65-1.35 m s -1 and a pH set-point for CO 2 injection of 8.0. Highest volumetric (0.08 ± 0.01 g L -1 d -1 ) and areal (20.3 ± 3.2 g m -2 d -1 ) biomass productivities were attained in the 100-m 3 PBR compared to those of the 35-m 3 PBR (0.05 ± 0.02 g L -1 d -1 and 13.5 ± 4.3 g m -2 d -1 , respectively). Lipid contents were similar in both PBRs (9-10% of ash free dry weight). CO 2 sequestration was followed in the 100-m 3 PBR, revealing a mean CO 2 mitigation efficiency of 65% and a biomass to carbon ratio of 1.80. Tetraselmis sp. CTP4 is thus a robust candidate for industrial-scale production with promising biomass productivities and photosynthetic efficiencies up to 3.5% of total solar irradiance.

Predictors of hospital re-admissions among Hispanics with hepatitis C-related cirrhosis.

PubMed

Atla, Pradeep R; Sheikh, Muhammad Y; Gill, Firdose; Kundu, Rabindra; Choudhury, Jayanta

2016-01-01

Hospital re-admissions in decompensated cirrhosis are associated with worse patient outcomes. Hispanics have a disproportionately high prevalence of hepatitis C virus (HCV)-related morbidity and mortality. The goal of this study was to evaluate the factors affecting re-admission rates among Hispanics with HCV-related cirrhosis. A total of 292 consecutive HCV-related cirrhosis admissions (Hispanics 189, non-Hispanics 103) from January 2009 to December 2012 were retrospectively reviewed; 132 were cirrhosis-related re-admissions. The statistical analysis was performed using STATA version 11.1. Chi-square/Fisher's exact and Student's t-tests were used to compare categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to identify predictors for hospital readmissions. Among the 132 cirrhosis-related readmissions, 71% were Hispanics while 29% were non-Hispanics (P=0.035). Hepatic encephalopathy (HE) and esophageal variceal hemorrhage were the most frequent causes of the first and subsequent readmissions. Hispanics with readmissions had a higher Child-Turcotte-Pugh (CTP) class (B and C) and higher model for end-stage liver disease (MELD) scores (≥15), as well as a higher incidence of alcohol use, HE, spontaneous bacterial peritonitis, hepatocellular carcinoma, and varices (P<0.05). The majority of the study patients (81%) had MELD scores <15. Multivariate regression analysis identified alcohol use (OR 2.63; 95%CI 1.1-6.4), HE (OR 5.5; 95%CI 2-15.3), varices (OR 3.2; 95%CI 1.3-8.2), and CTP class (OR 3.3; 95%CI 1.4-8.1) as predictors for readmissions among Hispanics. CTP classes B and C, among other factors, were the major predictors for hospital readmissions in Hispanics with HCV-related cirrhosis. The majority of these readmissions were due to HE and variceal hemorrhage.

Characterization of printed planar electromagnetic coils using digital extrusion and roll-to-roll flexographic processes

NASA Astrophysics Data System (ADS)

Rickard, Scott

Electromagnets are a crucial component in a wide range of more complex electrical devices due to their ability to turn electrical energy into mechanical energy and vice versa. The trend for electronics becoming smaller and lighter has led to increased interest in using flat, planar electromagnetic coils, which have been shown to perform better at scaled down sizes. The two-dimensional geometry of a planar electromagnetic coil yields itself to be produced by a roll-to-roll additive manufacturing process. The emergence of the printed electronics field, which uses traditional printing processes to pattern functional inks, has led to new methods of mass-producing basic electrical components. The ability to print a planar electromagnetic coil using printed electronics could rival the traditional subtractive and semi-subtractive PCB process of manufacturing. The ability to print lightweight planar electromagnetic coils on flexible substrates could lead to their inclusion into intelligent packaging applications and could have specific use in actuating devices, transformers, and electromagnetic induction applications such as energy harvesting or wireless charging. In attempts to better understand the limitations of printing planar electromagnetic coils, the effect that the design parameters of the planar coils have on the achievable magnetic field strength were researched. A comparison between prototyping methods of digital extrusion and manufacturing scale flexographic printing are presented, discussing consistency in the printed coils and their performance in generating magnetic fields. A method to predict the performance of these planar coils is introduced to allow for design within required needs of an application. Results from the research include a demonstration of a printed coil being used in a flat speaker design, working off of actuating principles.

Binary black holes' effects on electromagnetic fields.

PubMed

Palenzuela, Carlos; Anderson, Matthew; Lehner, Luis; Liebling, Steven L; Neilsen, David

2009-08-21

In addition to producing gravitational waves, the dynamics of a binary black hole system could induce emission of electromagnetic radiation by affecting the behavior of plasmas and electromagnetic fields in their vicinity. We here study how the electromagnetic fields are affected by a pair of orbiting black holes through the merger. In particular, we show how the binary's dynamics induce a variability in possible electromagnetically induced emissions as well as a possible enhancement of electromagnetic fields during the late-merge and merger epochs. These time dependent features will likely leave their imprint in processes generating detectable emissions and can be exploited in the detection of electromagnetic counterparts of gravitational waves.

Computers in the Schools: State/Provincial Implications.

ERIC Educational Resources Information Center

Thiessen, S. J.

The Alberta goverment has attempted to systematically address educational computing issues through programs of the provincial (K-12) education department (Alberta Education), which have included the development of computer literacy curricula for elementary, junior, and senior high schools; the Computer Technology Project (CTP); evaluation studies;…

21 CFR 1141.12 - Incorporation by reference of required warnings.

Code of Federal Regulations, 2013 CFR

2013-04-01

... SERVICES (CONTINUED) TOBACCO PRODUCTS CIGARETTE PACKAGE AND ADVERTISING WARNINGS Cigarette Package and Advertising Warnings § 1141.12 Incorporation by reference of required warnings. “Cigarette Required Warnings..., ATTN: Cigarette Warning File Requests, 9200 Corporate Blvd., Rockville, MD 20850, 1-877-CTP-1373, or...

Identification of hydrophobic amino acids required for lipid activation of C. elegans CTP:phosphocholine cytidylyltransferase.

PubMed

Braker, Jay D; Hodel, Kevin J; Mullins, David R; Friesen, Jon A

2009-12-01

CTP:phosphocholine cytidylyltransferase (CCT), critical for phosphatidylcholine biosynthesis, is activated by translocation to the membrane surface. The lipid activation region of Caenorhabditis elegans CCT is between residues 246 and 266 of the 347 amino acid polypeptide, a region proposed to form an amphipathic alpha helix. When leucine 246, tryptophan 249, isoleucine 256, isoleucine 257, or phenylalanine 260, on the hydrophobic face of the helix, were changed individually to serine low activity was observed in the absence of lipid vesicles, similar to wild-type CCT, while lipid stimulated activity was reduced compared to wild-type CCT. Mutational analysis of phenylalanine 260 implicated this residue as a contributor to auto-inhibition of CCT while mutation of L246, W249, I256, and I257 simultaneously to serine resulted in significantly higher activity in the absence of lipid vesicles and an enzyme that was not lipid activated. These results support a concerted mechanism of lipid activation that requires multiple residues on the hydrophobic face of the putative amphipathic alpha helix.

Management of Liver Cancer Argon-helium Knife Therapy with Functional Computer Tomography Perfusion Imaging.

PubMed

Wang, Hongbo; Shu, Shengjie; Li, Jinping; Jiang, Huijie

2016-02-01

The objective of this study was to observe the change in blood perfusion of liver cancer following argon-helium knife treatment with functional computer tomography perfusion imaging. Twenty-seven patients with primary liver cancer treated with argon-helium knife and were included in this study. Plain computer tomography (CT) and computer tomography perfusion (CTP) imaging were conducted in all patients before and after treatment. Perfusion parameters including blood flows, blood volume, hepatic artery perfusion fraction, hepatic artery perfusion, and hepatic portal venous perfusion were used for evaluating therapeutic effect. All parameters in liver cancer were significantly decreased after argon-helium knife treatment (p < 0.05 to all). Significant decrease in hepatic artery perfusion was also observed in pericancerous liver tissue, but other parameters kept constant. CT perfusion imaging is able to detect decrease in blood perfusion of liver cancer post-argon-helium knife therapy. Therefore, CTP imaging would play an important role for liver cancer management followed argon-helium knife therapy. © The Author(s) 2014.

Neutron transport analysis for nuclear reactor design

DOEpatents

Vujic, Jasmina L.

1993-01-01

Replacing regular mesh-dependent ray tracing modules in a collision/transfer probability (CTP) code with a ray tracing module based upon combinatorial geometry of a modified geometrical module (GMC) provides a general geometry transfer theory code in two dimensions (2D) for analyzing nuclear reactor design and control. The primary modification of the GMC module involves generation of a fixed inner frame and a rotating outer frame, where the inner frame contains all reactor regions of interest, e.g., part of a reactor assembly, an assembly, or several assemblies, and the outer frame, with a set of parallel equidistant rays (lines) attached to it, rotates around the inner frame. The modified GMC module allows for determining for each parallel ray (line), the intersections with zone boundaries, the path length between the intersections, the total number of zones on a track, the zone and medium numbers, and the intersections with the outer surface, which parameters may be used in the CTP code to calculate collision/transfer probability and cross-section values.

Neutron transport analysis for nuclear reactor design

DOEpatents

Vujic, J.L.

1993-11-30

Replacing regular mesh-dependent ray tracing modules in a collision/transfer probability (CTP) code with a ray tracing module based upon combinatorial geometry of a modified geometrical module (GMC) provides a general geometry transfer theory code in two dimensions (2D) for analyzing nuclear reactor design and control. The primary modification of the GMC module involves generation of a fixed inner frame and a rotating outer frame, where the inner frame contains all reactor regions of interest, e.g., part of a reactor assembly, an assembly, or several assemblies, and the outer frame, with a set of parallel equidistant rays (lines) attached to it, rotates around the inner frame. The modified GMC module allows for determining for each parallel ray (line), the intersections with zone boundaries, the path length between the intersections, the total number of zones on a track, the zone and medium numbers, and the intersections with the outer surface, which parameters may be used in the CTP code to calculate collision/transfer probability and cross-section values. 28 figures.

Electromagnetic containerless processing requirements and recommended facility concept and capabilities for space lab

NASA Technical Reports Server (NTRS)

Frost, R. T.; Bloom, H. L.; Napaluch, L. J.; Stockhoff, E. H.; Wouch, G.

1974-01-01

Containerless melting, reaction, and solidification experiments and processes which potentially can lead to new understanding of material science and production of new or improved materials in the weightless space environment are reviewed in terms of planning for spacelab. Most of the experiments and processes discussed are amenable to the employment of electromagnetic position control and electromagnetic induction or electron beam heating and melting. The spectrum of relevant properties of materials, which determine requirements for a space laboratory electromagnetic containerless processing facility are reviewed. Appropriate distributions and associated coil structures are analyzed and compared on the basis of efficiency, for providing the functions of position sensing, control, and induction heating. Several coil systems are found capable of providing these functions. Exchangeable modular coils in appropriate sizes are recommended to achieve the maximum power efficiencies, for a wide range of specimen sizes and resistivities, in order to conserve total facility power.

Electromagnetic Evidence of Altered Visual Processing in Autism

ERIC Educational Resources Information Center

Neumann, Nicola; Dubischar-Krivec, Anna M.; Poustka, Fritz; Birbaumer, Niels; Bolte, Sven; Braun, Christoph

2011-01-01

Individuals with autism spectrum disorder (ASD) demonstrate intact or superior local processing of visual-spatial tasks. We investigated the hypothesis that in a disembedding task, autistic individuals exhibit a more local processing style than controls, which is reflected by altered electromagnetic brain activity in response to embedded stimuli…

Particle simulation of electromagnetic emissions from electrostatic instability driven by an electron ring beam on the density gradient

NASA Astrophysics Data System (ADS)

Horký, Miroslav; Omura, Yoshiharu; Santolík, Ondřej

2018-04-01

This paper presents the wave mode conversion between electrostatic and electromagnetic waves on the plasma density gradient. We use 2-D electromagnetic code KEMPO2 implemented with the generation of density gradient to simulate such a conversion process. In the dense region, we use ring beam instability to generate electron Bernstein waves and we study the temporal evolution of wave spectra, velocity distributions, Poynting flux, and electric and magnetic energies to observe the wave mode conversion. Such a conversion process can be a source of electromagnetic emissions which are routinely measured by spacecraft on the plasmapause density gradient.

Influence of electromagnetic field on soliton-mediated charge transport in biological systems.

PubMed

Brizhik, Larissa

2015-01-01

It is shown that electromagnetic fields affect dynamics of Davydov's solitons which provide charge transport processes in macromolecules during metabolism of the system. There is a resonant frequency of the field at which it can cause the transition of electrons from bound soliton states into delocalised states. Such decay of solitons reduces the effectiveness of charge transport, and, therefore, inhibits redox processes. Solitons radiate their own electromagnetic field of characteristic frequency determined by their average velocity. This self-radiated field leads to synchronization of soliton dynamics and charge transport processes, and is the source of the coherence in the system. Exposition of the system to the oscillating electromagnetic field of the frequency, which coincides with the eigen-frequency of solitons can enhance eigen-radiation of solitons, and, therefore, will enhance synchronization of charge transpor, stimulate the redox processes and increase coherence in the system. Electromagnetic oscillating field causes also ratchet phenomenon of solitons, i.e., drift of solitons in macromolecules in the presence of unbiased periodic field. Such additional drift enhances the charge transport processes. It is shown that temperature facilitates the ratchet drift. In particular, temperature fluctuations lead to the lowering of the critical value of the intensity and period of the field, above which the drift of solitons takes place. Moreover, there is a stochastic resonance in the soliton dynamics in external electromagnetic fields. This means, that there is some optimal temperature at which the drift of solitons is maximal.

The REFANI-S study protocol: a non-randomised cluster controlled trial to assess the role of an unconditional cash transfer, a non-food item kit, and free piped water in reducing the risk of acute malnutrition among children aged 6-59 months living in camps for internally displaced persons in the Afgooye corridor, Somalia.

PubMed

Jelle, Mohamed; Grijalva-Eternod, Carlos S; Haghparast-Bidgoli, Hassan; King, Sarah; Cox, Cassy L; Skordis-Worrall, Jolene; Morrison, Joanna; Colbourn, Timothy; Fottrell, Edward; Seal, Andrew J

2017-07-06

The prevalence of acute malnutrition is often high in emergency-affected populations and is associated with elevated mortality risk and long-term health consequences. Increasingly, cash transfer programmes (CTP) are used instead of direct food aid as a nutritional intervention, but there is sparse evidence on their nutritional impact. We aim to understand whether CTP reduces acute malnutrition and its known risk factors. A non-randomised, cluster-controlled trial will assess the impact of an unconditional cash transfer of US$84 per month for 5 months, a single non-food items kit, and free piped water on the risk of acute malnutrition in children, aged 6-59 months. The study will take place in camps for internally displaced persons (IDP) in peri-urban Mogadishu, Somalia. A cluster will consist of one IDP camp and 10 camps will be allocated to receive the intervention based on vulnerability targeting criteria. The control camps will then be selected from the same geographical area. Needs assessment data indicates small differences in vulnerability between camps. In each trial arm, 120 households will be randomly sampled and two detailed household surveys will be implemented at baseline and 3 months after the initiation of the cash transfer. The survey questionnaire will cover risk factors for malnutrition including household expenditure, assets, food security, diet diversity, coping strategies, morbidity, WASH, and access to health care. A community surveillance system will collect monthly mid-upper arm circumference measurements from all children aged 6-59 months in the study clusters to assess the incidence of acute malnutrition over the duration of the intervention. Process evaluation data will be compiled from routine quantitative programme data and primary qualitative data collected using key informant interviews and focus group discussions. The UK Department for International Development will provide funding for this study. The European Civil Protection and Humanitarian Aid Operations will fund the intervention. Concern Worldwide will implement the intervention as part of their humanitarian programming. This non-randomised cluster controlled trial will provide needed evidence on the role of unconditional CTP in reducing the risk of acute malnutrition among IDP in this context. ISRCTN29521514 . Registered 19 January 2016.

Electromagnetic bonding of plastics to aluminum

NASA Technical Reports Server (NTRS)

Sheppard, A. T.; Silbert, L.

1980-01-01

Electromagnetic curing is used to bond strain gage to aluminum tensile bar. Electromagnetic energy heats only plastic/metal interface by means of skin effect, preventing degradation of heat-treated aluminum. Process can be easily applied to other metals joined by high-temperature-curing plastic adhesives.

Integrating long-offset transient electromagnetics (LOTEM) with seismics in an exploration environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strack, K.M.; Vozoff, K.

The applications of electromagnetics have increased in the past two decades because of an improved understanding of the methods, improves service availability, and the increased focus of exploration in the more complex reservoir characterization issues. For electromagnetic methods surface applications for hydrocarbon Exploration and Production are still a special case, while applications in borehole and airborne research and for engineering and environmental objectives are routine. In the past, electromagnetic techniques, in particular deep transient electromagnetics, made up a completely different discipline in geophysics, although many of the principles are similar to the seismic one. With an understanding of the specificmore » problems related to data processing initially and then acquisition, the inclusion of principles learned from seismics happened almost naturally. Initially, the data processing was very similar to seismic full-waveform processing. The hardware was also changed to include multichannel acquisition systems, and the field procedures became very similar to seismic surveying. As a consequence, the integration and synergism of the interpretation process is becoming almost automatic. The long-offset transient electromagnetic (LOTEM) technique will be summarized from the viewpoint of its similarity to seismics. The complete concept of the method will also be reviewed. An interpretation case history that integrates seismic and LOTEM from a hydrocarbon area in China clearly demonstrates the limitations and benefits of the method.« less

Real-time holographic surveillance system

DOEpatents

Collins, H. Dale; McMakin, Douglas L.; Hall, Thomas E.; Gribble, R. Parks

1995-01-01

A holographic surveillance system including means for generating electromagnetic waves; means for transmitting the electromagnetic waves toward a target at a plurality of predetermined positions in space; means for receiving and converting electromagnetic waves reflected from the target to electrical signals at a plurality of predetermined positions in space; means for processing the electrical signals to obtain signals corresponding to a holographic reconstruction of the target; and means for displaying the processed information to determine nature of the target. The means for processing the electrical signals includes means for converting analog signals to digital signals followed by a computer means to apply a backward wave algorithm.

Examination of electromagnetic powers with the example of a uc(Faraday) disc dynamo

NASA Astrophysics Data System (ADS)

Reich, Felix A.; Müller, Wolfgang H.

2018-03-01

This paper studies the mathematical form of electromagnetic powers and their influence on the balance of energy by using the example of a uc(Faraday) disc. First, two forms of energy (and balances thereof) are discussed. These employ different forms of powers, which can be distinguished w.r.t. their physical origins and their interpretations in context with the notions of supply and production. The stationary uc(Faraday) disc experiment is modeled following the description by Kovetz (Electromagnetic theory, Oxford University Press, Oxford, 2000). Concepts for formulating the electromagnetic field equations for the rotating disc are discussed, and the corresponding approximate analytical solutions are presented. Based on the obtained electromagnetic fields, the powers of the disc are analyzed for a stationary process. The conversion of mechanical power to heating and electromagnetic powering of an external resistor is explained. The paper concludes with the computation of the time evolution of the angular velocity for a magnetically induced breaking process of the disc.

76 FR 52994 - Application for a License To Export Heavy Water

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-24

... NUCLEAR REGULATORY COMMISSION Application for a License To Export Heavy Water Pursuant to 10 CFR... (liters). producing an active water). pharmaceutical ingredient known as CTP-499, which incorporates heavy water as the source of deuterium to achieve the hydrogen-deuterium exchange. November 30, 2010 December...

Optimization Review: Bunker Hill Mining and Metallurgical Complex Superfund Site, Central Treatment Plant (CTP), Kellogg, Shoshone County, Idaho

EPA Pesticide Factsheets

The Bunker Hill Mining and Metallurgical Complex Superfund Site includes all areas of the Coeur d’Alene Basin where mining-related contamination occurred and encompasses a 21-square mile “Box” along Interstate 90 surrounding the former smelter complex.

B Removal by Zr Addition in Electromagnetic Solidification Refinement of Si with Si-Al Melt

NASA Astrophysics Data System (ADS)

Lei, Yun; Ma, Wenhui; Sun, Luen; Dai, Yongnian; Morita, Kazuki

2016-02-01

This study investigated a new process of enhancing B removal by adding small amounts of Zr in the electromagnetic solidification refinement of Si with Si-Al melt. B in Si was removed by as much as 97.2 pct by adding less than 1057 ppma Zr, and the added Zr was removed by as much as 99.7 pct. In addition, Zr is more effective in enhancing B removal than Ti in the same electromagnetic solidification refining process.

Ultrastructural Study on Ultra-Low Frequency Electromagnetic Fields and Transfer Factor Effects on Skin Ulcers

NASA Astrophysics Data System (ADS)

Cadena, M. S. Reyes; Chapul, L. Sánchez; Pérez, Javiér; García, M. N. Jiménez; López, M. A. Jiménez; Espíndola, M. E. Sánchez; Perez, R. Paniagua; Hernández, N. A.; Paniagua, G.; Uribe, F.; Nava, J. J. Godina; Segura, M. A. Rodríguez

2008-08-01

We determined the effect of 120Hz ultra low frequency electromagnetic field (ELF) on the healing process of skin in 20 Wistar rats distributed in four groups in which chronic dermal ulcers had been produced. The first two groups received a dose of the transfer factor and interferon-beta (IFN-β) every 24 h during 12 days. The third group (positive control) received only electromagnetic field (ELF) sessions, and in the fourth group (negative control), no treatment was applied. The electromagnetic field was applied through a Helmholtz coils; 30 Gauss of intensity. Results shown histological changes that improve the healing process in animals subjected to ELF together with the transfer factor.

Dietary uridine-5'-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats.

PubMed

Wang, Lei; Pooler, Amy M; Albrecht, Meredith A; Wurtman, Richard J

2005-01-01

Membrane phospholipids like phosphatidylcholine (PC) are required for cellular growth and repair, and specifically for synaptic function. PC synthesis is controlled by cellular levels of its precursor, cytidine-5'-diphosphate choline (CDP-choline), which is produced from cytidine triphosphate (CTP) and phosphocholine. In rat PC12 cells exogenous uridine was shown to elevate intracellular CDP-choline levels, by promoting the synthesis of uridine triphosphate (UTP), which was partly converted to CTP. In such cells uridine also enhanced the neurite outgrowth produced by nerve growth factor (NGF). The present study assessed the effect of dietary supplementation with uridine-5'-monophosphate disodium (UMP-2Na+, an additive in infant milk formulas) on striatal dopamine (DA) release in aged rats. Male Fischer 344 rats consumed either a control diet or one fortified with 2.5% UMP for 6 wk, ad libitum. In vivo microdialysis was then used to measure spontaneous and potassium (K+)-evoked DA release in the right striatum. Potassium (K+)-evoked DA release was significantly greater among UMP-treated rats, i.e., 341+/-21% of basal levels vs. 283+/-9% of basal levels in control rats (p<0.05); basal DA release was unchanged. In general, each animal's K+-evoked DA release correlated with its striatal DA content, measured postmortem. The levels of neurofilament-70 and neurofilament-M proteins, biomarkers of neurite outgrowth, increased to 182+/-25% (p<0.05) and 221+/-34% (p<0.01) of control values, respectively, with UMP consumption. Hence, UMP treatment not only enhances membrane phosphatide production but also can modulate two membrane-dependent processes, neurotransmitter release and neurite outgrowth, in vivo.

Identification and Characterization of a Chloroplast-Targeted Obg GTPase in Dendrobium officinale.

PubMed

Chen, Ji; Deng, Feng; Deng, Mengsheng; Han, Jincheng; Chen, Jianbin; Wang, Li; Yan, Shen; Tong, Kai; Liu, Fan; Tian, Mengliang

2016-12-01

Bacterial homologous chloroplast-targeted Obg GTPases (ObgCs) belong to the plant-typical Obg group, which is involved in diverse physiological processes during chloroplast development. However, the evolutionarily conserved function of ObgC in plants remains elusive and requires further investigation. In this study, we identified DoObgC from an epiphytic plant Dendrobium officinale and demonstrated the characteristics of DoObgC. Sequence analysis indicated that DoObgC is highly conserved with other plant ObgCs, which contain the chloroplast transit peptide (cTP), Obg fold, G domain, and OCT regions. The C terminus of DoObgC lacking the chloroplast-targeting cTP region, DoObgC Δ1-160 , showed strong similarity to ObgE and other bacterial Obgs. Overexpression of DoObgC Δ1-160 in Escherichia coli caused slow cell growth and an increased number of elongated cells. This phenotype was consistent with the phenotype of cells overexpressing ObgE. Furthermore, the expression of recombinant DoObgC Δ1-160 enhanced the cell persistence of E. coli to streptomycin. Results of transient expression assays revealed that DoObgC was localized to chloroplasts. Moreover, we demonstrated that DoObgC could rescue the embryotic lethal phenotype of the Arabidopsis obgc-t mutant, suggesting that DoObgC is a functional homolog to Arabidopsis AtObgC in D. officinale. Gene expression profiles showed that DoObgC was expressed in leaf-specific and light-dependent patterns and that DoObgC responded to wounding treatments. Our previous and present studies reveal that ObgC has an evolutionarily conserved role in ribosome biogenesis to adapt chloroplast development to the environment.

Electromagnetic dissociation of U-238 in heavy-ion collisions at 120 MeV/A

NASA Astrophysics Data System (ADS)

Justice, M. L.

1991-04-01

This thesis describes a measurement of the heavy-ion induced electromagnetic dissociation of a 120 MeV/A U-238 beam incident on five targets: Be-9, Al-27, Cu, Ag, and U. Electromagnetic dissociation at this beam energy is essentially a two step process involving the excitation of a giant resonance followed by particle decay. At 120 MeV/A there is predicted to be a significant contribution of the giant quadrupole resonance to the EMD cross sections. The specific exit channel which was looked at was projectile fission. The two fission fragments were detected in coincidence by an array of solid-state (Delta)E-E detectors, allowing the changes of the fragments to be determined to within (+/-) .5 units. The events were sorted on the basis of the sums of the fragments' charges, acceptance corrections were applied, and total cross sections for the most peripheral events were determined. Electromagnetic fission at the beam energy of this experiment always leads to a true charge sum of 92. Due to the imperfect resolution of the detectors, charge sums of 91 and 93 were included in order to account for all of the electromagnetic fission events. The experimentally observed cross sections are due to nuclear interaction processes as well as electromagnetic processes. Under the conditions of this experiment, the cross sections for the beryllium target are almost entirely due to nuclear processes. The nuclear cross sections for the other four targets were determined by extrapolation from the beryllium data using a geometrical scaling model. After subtraction of the nuclear cross sections, the resulting electromagnetic cross sections are compared to theoretical calculations based on the equivalent photon approximation. Systematic uncertainties are discussed and suggestions for improving the experiment are given.

Electromagnetic structure of the proton within the CP-violation hypothesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krutov, A. F., E-mail: krutov@ssu.samara.ru; Kudinov, M. Yu., E-mail: kudinov@ssu.samara.ru

2013-11-15

The so-called non-Rosenbluth behavior of the proton electromagnetic form factors can be explained within the hypothesis of CP violation in electromagnetic processes involving composite systems of strongly interacting particles. It is shown that this hypothesis leads to the appearance of an additional, anapole, form factor of the proton. The proton electromagnetic form factors, including the anapole form factor, are estimated on the basis of experimental data on elastic electron-proton scattering.

Electromagnetic processes in nucleus-nucleus collisions relating to space radiation research

NASA Technical Reports Server (NTRS)

Norbury, John W.

1992-01-01

Most of the papers within this report deal with electromagnetic processes in nucleus-nucleus collisions which are of concern in the space radiation program. In particular, the removal of one and two nucleons via both electromagnetic and strong interaction processes has been extensively investigated. The theory of relativistic Coulomb fission has also been developed. Several papers on quark models also appear. Finally, note that the theoretical methods developed in this work have been directly applied to the task of radiation protection of astronauts. This has been done by parameterizing the theoretical formalism in such a fashion that it can be used in cosmic ray transport codes.

Real-time holographic surveillance system

DOEpatents

Collins, H.D.; McMakin, D.L.; Hall, T.E.; Gribble, R.P.

1995-10-03

A holographic surveillance system is disclosed including means for generating electromagnetic waves; means for transmitting the electromagnetic waves toward a target at a plurality of predetermined positions in space; means for receiving and converting electromagnetic waves reflected from the target to electrical signals at a plurality of predetermined positions in space; means for processing the electrical signals to obtain signals corresponding to a holographic reconstruction of the target; and means for displaying the processed information to determine nature of the target. The means for processing the electrical signals includes means for converting analog signals to digital signals followed by a computer means to apply a backward wave algorithm. 21 figs.

Cell Therapy Regulation in Taiwan

PubMed Central

Chen, Yuan-Chuan; Cheng, Hwei-Fang; Yeh, Ming-Kung

2017-01-01

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. PMID:27697103

Changes in metal properties after thermal and electric impulse processing

NASA Astrophysics Data System (ADS)

Shaburova, N. A.

2015-04-01

The results of the experiments on processing metal melts by powerful electromagnetic impulses are given. The generator used in the experiments has the following characteristics: pulse height - 10KV, duration - 1ns, leading edge - 0.1ns, repetition rate - 1KHz, the output - 100KWt. The duration of the processing is 10-15min. The comparative analysis of the processed and unprocessed samples results in the changes of structure, increase of density, solidity, plasticity and resilience of cast metal. The result analysis of different external physical processing methods on alloys shows full agreement with the results of the ultrasonic processing of metals. The hypothesis of ultrasonic shock wave formation at the pulse front was adopted as the main mechanism of the electromagnetic impulse impact on alloys. The theoretical part of the research describes the transformation process of electromagnetic impulses into acoustic ones.

Ultrastructural Study on Ultra-Low Frequency Electromagnetic Fields and Transfer Factor Effects on Skin Ulcers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cadena, M. S. Reyes; Chapul, L. Sanchez; Perez, Javier

2008-08-11

We determined the effect of 120Hz ultra low frequency electromagnetic field (ELF) on the healing process of skin in 20 Wistar rats distributed in four groups in which chronic dermal ulcers had been produced. The first two groups received a dose of the transfer factor and interferon-beta (IFN-{beta}) every 24 h during 12 days. The third group (positive control) received only electromagnetic field (ELF) sessions, and in the fourth group (negative control), no treatment was applied. The electromagnetic field was applied through a Helmholtz coils; 30 Gauss of intensity. Results shown histological changes that improve the healing process in animalsmore » subjected to ELF together with the transfer factor.« less

Electromagnetic Wave Absorption Coating Material with Self-Healing Properties.

PubMed

Wang, Ya-Min; Pan, Min; Liang, Xiang-Yong; Li, Bang-Jing; Zhang, Sheng

2017-12-01

Electromagnetic wave absorption coatings can effectively minimize electromagnetic radiation and are widely used in the military and civil field. However, even small scratches on the coating can lead to a large decline of absorption ability and bring serious consequences. To enhance the lifetime of electromagnetic wave absorbing coating, a kind of self-healing electromagnetic wave absorbing coating is developed by introducing host-guest interactions between the absorbing fillers and polymer matrix. After being damaged, the cracks on this coating can be healed completely with the aid of small amounts of water. Simultaneously, the electromagnetic absorbing ability of the coating is restored along with the self-healing process. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spectral perspective on the electromagnetic activity of cells.

PubMed

Kučera, Ondrej; Červinková, Kateřina; Nerudová, Michaela; Cifra, Michal

2015-01-01

In this mini-review, we summarize the current hypotheses, theories and experimental evidence concerning the electromagnetic activity of living cells. We systematically classify the bio-electromagnetic phenomena in terms of frequency and we assess their general acceptance in scientific community. We show that the electromagnetic activity of cells is well established in the low frequency range below 1 kHz and on optical wavelengths, while there is only limited evidence for bio-electromagnetic processes in radio- frequency and millimeter-wave ranges. This lack of generally accepted theory or trustful experimental results is the cause for controversy which accompanies this topic. We conclude our review with the discussion of the relevance of the electromagnetic activity of cells to human medicine.

Electromagnetic perception and individual features of human beings.

PubMed

Lebedeva, N N; Kotrovskaya, T I

2001-01-01

An investigation was made of the individual reactions of human subjects exposed to electromagnetic fields. We performed the study on 86 volunteers separated into two groups. The first group was exposed to the electromagnetic field of infralow frequencies, whereas the second group was exposed to the electromagnetic field of extremely high frequencies. We found that the electromagnetic perception of human beings correlated with their individual features, such as EEG parameters, the critical frequency of flash merging, and the electric current sensitivity. Human subjects who had a high-quality perception of electromagnetic waves showed an optimal balance of cerebral processes, an excellent functional state of the central nervous system, and a good decision criterion.

Research on radiation characteristic of plasma antenna through FDTD method.

PubMed

Zhou, Jianming; Fang, Jingjing; Lu, Qiuyuan; Liu, Fan

2014-01-01

The radiation characteristic of plasma antenna is investigated by using the finite-difference time-domain (FDTD) approach in this paper. Through using FDTD method, we study the propagation of electromagnetic wave in free space in stretched coordinate. And the iterative equations of Maxwell equation are derived. In order to validate the correctness of this method, we simulate the process of electromagnetic wave propagating in free space. Results show that electromagnetic wave spreads out around the signal source and can be absorbed by the perfectly matched layer (PML). Otherwise, we study the propagation of electromagnetic wave in plasma by using the Boltzmann-Maxwell theory. In order to verify this theory, the whole process of electromagnetic wave propagating in plasma under one-dimension case is simulated. Results show that Boltzmann-Maxwell theory can be used to explain the phenomenon of electromagnetic wave propagating in plasma. Finally, the two-dimensional simulation model of plasma antenna is established under the cylindrical coordinate. And the near-field and far-field radiation pattern of plasma antenna are obtained. The experiments show that the variation of electron density can introduce the change of radiation characteristic.

Fractional models of seismoacoustic and electromagnetic activity

NASA Astrophysics Data System (ADS)

Shevtsov, Boris; Sheremetyeva, Olga

2017-10-01

Statistical models of the seismoacoustic and electromagnetic activity caused by deformation disturbances are considered on the basis of compound Poisson process and its fractional generalizations. Wave representations of these processes are used too. It is discussed five regimes of deformation activity and their role in understanding of the earthquakes precursors nature.

Propagation of electromagnetic wave in dusty plasma and the influence of dust size distribution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Hui; China Research Institute of Radio Wave Propagation; Wu, Jian

The effect of charged dust particle and their size distribution on the propagation of electromagnetic wave in a dusty plasma is investigated. It is shown that the additional collision mechanism provided by charged dust particles can significantly alter the electromagnetic properties of a plasma, leading to the appearance of attenuation of electromagnetic wave through dusty plasma. The attenuation coefficient mainly depends on the dust density, radius, and the charge numbers on the dust surface. The results described here will be used to enhance understanding of electromagnetic wave propagation processed in space and laboratory dusty plasma.

Observer Training Manual for the Changing Teacher Practice Study. Revised Manual.

ERIC Educational Resources Information Center

Barnes, Susan

This observer training manual was developed as a central component of a research effort, Changing Teacher Practice (CTP), which was designed to increase the frequency of effective teaching behaviors and staff development strategies in an ongoing school system. The observations focused on two major aspects of classroom teaching--instruction and…

Evaluation of LEAA Funded Courts Training Programs. Volume I.

ERIC Educational Resources Information Center

McManis Associates, Inc., Washington, DC.

An impact evaluation of eight courts training project (CTP) institutes funded by the Law Enforcement Assistance Administration was conducted. After a literature search and visits to potential evaluation sites in all fifty states, twelve sites were selected from a random stratified sample of court systems. Data were obtained from 1047 respondents…

78 FR 38055 - Building Research Capacity in Global Tobacco Product Regulation Program (U18)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-25

... Monitoring Database. Examples of Global Tobacco Research Reports/White Papers: [cir] WHO report on the global...] Building Research Capacity in Global Tobacco Product Regulation Program (U18) AGENCY: Food and Drug... availability of grant funds for the support of the Center for Tobacco Product's (CTP's) Building Research...

The Round Table on Computer Performance Metrics for Export Control: Discussions and Results

DTIC Science & Technology

1997-12-01

eligibility, use the CTP parameter to the exclusion of other technical parameters for computers classified under ECCN 4A003.a, .b and .c, except of...parameters specified as Missile Technology (MT) concerns or 4A003.e (equipment performing analog-to-digital conversions exceeding the limits in ECCN

Binding of ATP by pertussis toxin and isolated toxin subunits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hausman, S.Z.; Manclark, C.R.; Burns, D.L.

1990-07-03

The binding of ATP to pertussis toxin and its components, the A subunit and B oligomer, was investigated. Whereas, radiolabeled ATP bound to the B oligomer and pertussis toxin, no binding to the A subunit was observed. The binding of ({sup 3}H)ATP to pertussis toxin and the B oligomer was inhibited by nucleotides. The relative effectiveness of the nucleotides was shown to be ATP > GTP > CTP > TTP for pertussis toxin and ATP > GTP > TTP > CTP for the B oligomer. Phosphate ions inhibited the binding of ({sup 3}H)ATP to pertussis toxin in a competitive manner;more » however, the presence of phosphate ions was essential for binding of ATP to the B oligomer. The toxin substrate, NAD, did not affect the binding of ({sup 3}H)ATP to pertussis toxin, although the glycoprotein fetuin significantly decreased binding. These results suggest that the binding site for ATP is located on the B oligomer and is distinct from the enzymatically active site but may be located near the eukaryotic receptor binding site.« less

Ceramics Technology Project database: September 1991 summary report. [Materials for piston ring-cylinder liner for advanced heat/diesel engines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keyes, B.L.P.

1992-06-01

The piston ring-cylinder liner area of the internal combustion engine must withstand very-high-temperature gradients, highly-corrosive environments, and constant friction. Improving the efficiency in the engine requires ring and cylinder liner materials that can survive this abusive environment and lubricants that resist decomposition at elevated temperatures. Wear and friction tests have been done on many material combinations in environments similar to actual use to find the right materials for the situation. This report covers tribology information produced from 1986 through July 1991 by Battelle columbus Laboratories, Caterpillar Inc., and Cummins Engine Company, Inc. for the Ceramic Technology Project (CTP). All datamore » in this report were taken from the project's semiannual and bimonthly progress reports and cover base materials, coatings, and lubricants. The data, including test rig descriptions and material characterizations, are stored in the CTP database and are available to all project participants on request. Objective of this report is to make available the test results from these studies, but not to draw conclusions from these data.« less

Ceramics Technology Project database: September 1991 summary report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keyes, B.L.P.

1992-06-01

The piston ring-cylinder liner area of the internal combustion engine must withstand very-high-temperature gradients, highly-corrosive environments, and constant friction. Improving the efficiency in the engine requires ring and cylinder liner materials that can survive this abusive environment and lubricants that resist decomposition at elevated temperatures. Wear and friction tests have been done on many material combinations in environments similar to actual use to find the right materials for the situation. This report covers tribology information produced from 1986 through July 1991 by Battelle columbus Laboratories, Caterpillar Inc., and Cummins Engine Company, Inc. for the Ceramic Technology Project (CTP). All datamore » in this report were taken from the project`s semiannual and bimonthly progress reports and cover base materials, coatings, and lubricants. The data, including test rig descriptions and material characterizations, are stored in the CTP database and are available to all project participants on request. Objective of this report is to make available the test results from these studies, but not to draw conclusions from these data.« less

Micromethod for phosphonoformate inhibition assay of hepatitis B viral DNA polymerase.

PubMed

Lin, H J; Wu, P C; Lai, C L; Chak, W

1984-04-01

A micromethod for the specific measurement of hepatitis B viral DNA polymerase in serum is presented, based on the phosphonoformate inhibition assay (J Med Virol 12: 61-70, 1983). In the micromethod, sample volume is reduced to 120 microL and the ultracentrifugation step is eliminated. The method allows good discrimination between serum infected with hepatitis B virus and uninfected serum. The cutoff value for rate of nucleotide incorporation, based on assays of 41 serum specimens negative for hepatitis B serological markers, was about 15 nU/L (90th percentile). Serum containing hepatitis B surface and antigens exhibited rates of phosphonoformate-inhibitive nucleotide incorporation of 150 (SD 150) nU/L, with an upper 90th percentile range of 17 to 667 nU/L (n = 41). The micromethod makes use of commercially available [32P]dCTP (specific activity about 7000 kCi/mol). 125I-labeled dCTP was found to be unsuitable for this assay. Human DNA polymerases in serum are detected by this method but are excluded from the phosphonoformate-inhibitive fraction.

Nucleotide sequence of the gene encoding the nitrogenase iron protein of Thiobacillus ferrooxidans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pretorius, I.M.; Rawlings, D.E.; O'Neill, E.G.

1987-01-01

The DNA sequence was determined for the cloned Thiobacillus ferrooxidans nifH and part of the nifD genes. The DNA chains were radiolabeled with (..cap alpha..-/sup 32/P)dCTP (3000 Ci/mmol) or (..cap alpha..-/sup 35/S)dCTP (400 Ci/mmol). A putative T. ferrooxidans nifH promoter was identified whose sequences showed perfect consensus with those of the Klebsiella pneumoniae nif promoter. Two putative consensus upstream activator sequences were also identified. The amino acid sequence was deduced from the DNA sequence. In a comparison of nifH DNA sequences from T. ferrooxidans and eight other nitrogen-fixing microbes, a Rhizobium sp. isolated from Parasponia andersonii showed the greatest homologymore » (74%) and Clostridium pasteurianum (nifH1) showed the least homology (54%). In the comparison of the amino acid sequences of the Fe proteins, the Rhizobium sp. and Rhizobium japonicum showed the greatest homology (both 86%) and C. pasteurianum (nifH1 gene product) demonstrated the least homology (56%) to the T. ferrooxidans Fe protein.« less

The spatial distribution of cropland carbon transfer in Jilin province during 2014

NASA Astrophysics Data System (ADS)

Cai, Xintong; Meng, Jian; Li, Qiuhui; Gao, Shuang; Zhu, Xianjin

2018-01-01

Cropland carbon transfer (CCT, gC yr-1) is an important component in the carbon budget of terrestrial ecosystems. Analyzing the value of CCT and its spatial variation would provide a data basis for assessing the regional carbon balance. Based on the data from Jilin statistical yearbook 2015, we investigated the spatial variation of CCT in Jilin province during 2014. Results suggest that the CCT of Jilin province was 30.83 TgC, which exhibited a decreasing trend from the centre to the border but the west side was higher than the east. The magnitude of carbon transfer per area (MCT), which showed a similar spatial distribution with CCT, was the dominating component of CCT spatial distribution. The spatial distribution of MCT was jointly affected by that of the ratio of planting area to regional area (RPR) and carbon transfer per planting area (CTP), where RPR and CTP contributed 65.55% and 34.5% of MCT spatial distribution, respectively. Therefore, CCT in Jilin province spatially varied, which made it highly needed to consider the difference in CCT among regions when we assessing the regional carbon budget.

Cytidine Diphosphoramidate Kinase: An Enzyme Required for the Biosynthesis of the O-Methyl Phosphoramidate Modification in the Capsular Polysaccharides of Campylobacter jejuni.

PubMed

Taylor, Zane W; Raushel, Frank M

2018-04-17

Campylobacter jejuni, a leading cause of gastroenteritis, produces a capsular polysaccharide that is derivatized with a unique O-methyl phosphoramidate (MeOPN) modification. This modification contributes to serum resistance and invasion of epithelial cells. Previously, the first three biosynthetic steps for the formation of MeOPN were elucidated. The first step is catalyzed by a novel glutamine kinase (Cj1418), which catalyzes the adenosine triphosphate (ATP)-dependent phosphorylation of the amide nitrogen of l-glutamine. l-Glutamine phosphate is used by cytidine triphosphate (CTP):phosphoglutamine cytidylyltransferase (Cj1416) to displace pyrophosphate from CTP to generate cytidine diphosphate (CDP)-l-glutamine, which is then hydrolyzed by γ-glutamyl-CDP-amidate hydrolase (Cj1417) to form cytidine diphosphoramidate (CDP-NH 2 ). Here, we show that Cj1415 catalyzes the ATP-dependent phosphorylation of CDP-NH 2 to form 3'-phospho-cytidine-5'-diphosphoramidate. Cj1415 will also catalyze the phosphorylation of adenosine diphosphoramidate (ADP-NH 2 ) and uridine diphosphoramidate (UDP-NH 2 ) but at significantly reduced rates. It is proposed that Cj1415 be named cytidine diphosphoramidate kinase.

Biosynthesis of Nucleoside Diphosphoramidates in Campylobacter jejuni.

PubMed

Taylor, Zane W; Brown, Haley A; Holden, Hazel M; Raushel, Frank M

2017-11-21

Campylobacter jejuni is a pathogenic Gram-negative bacterium and a leading cause of food-borne gastroenteritis. C. jejuni produces a capsular polysaccharide (CPS) that contains a unique O-methyl phosphoramidate modification (MeOPN). Recently, the first step in the biosynthetic pathway for the assembly of the MeOPN modification to the CPS was elucidated. It was shown that the enzyme Cj1418 catalyzes the phosphorylation of the amide nitrogen of l-glutamine to form l-glutamine phosphate. In this investigation, the metabolic fate of l-glutamine phosphate was determined. The enzyme Cj1416 catalyzes the displacement of pyrophosphate from MgCTP by l-glutamine phosphate to form CDP-l-glutamine. The enzyme Cj1417 subsequently catalyzes the hydrolysis of CDP-l-glutamine to generate cytidine diphosphoramidate and l-glutamate. The structures of the two novel intermediates, CDP-l-glutamine and cytidine diphosphoramidate, were confirmed by 31 P nuclear magnetic resonance spectroscopy and mass spectrometry. It is proposed that the enzyme Cj1416 be named CTP:phosphoglutamine cytidylyltransferase and that the enzyme Cj1417 be named γ-glutamyl-CDP-amidate hydrolase.

Mechanism of Error-Free Bypass of the Environmental Carcinogen N-(2'-Deoxyguanosin-8-yl)-3-aminobenzanthrone Adduct by Human DNA Polymerase η.

PubMed

Patra, Amritraj; Politica, Dustin A; Chatterjee, Arindom; Tokarsky, E John; Suo, Zucai; Basu, Ashis K; Stone, Michael P; Egli, Martin

2016-11-03

The environmental pollutant 3-nitrobenzanthrone produces bulky aminobenzanthrone (ABA) DNA adducts with both guanine and adenine nucleobases. A major product occurs at the C8 position of guanine (C8-dG-ABA). These adducts present a strong block to replicative polymerases but, remarkably, can be bypassed in a largely error-free manner by the human Y-family polymerase η (hPol η). Here, we report the crystal structure of a ternary Pol⋅DNA⋅dCTP complex between a C8-dG-ABA-containing template:primer duplex and hPol η. The complex was captured at the insertion stage and provides crucial insight into the mechanism of error-free bypass of this bulky lesion. Specifically, bypass involves accommodation of the ABA moiety inside a hydrophobic cleft to the side of the enzyme active site and formation of an intra-nucleotide hydrogen bond between the phosphate and ABA amino moiety, allowing the adducted guanine to form a standard Watson-Crick pair with the incoming dCTP. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantized Electromagnetic-Field Propagation in General Non-Local and Non-Stationary Dispersive and Absorbing Media

NASA Astrophysics Data System (ADS)

Jacobs, Verne

Dynamical descriptions for the propagation of quantized electromagnetic fields, in the presence of environmental interactions, are systematically and self-consistently developed in the complimentary Schrödinger and Heisenberg pictures. An open-systems (non-equilibrium) quantum-electrodynamics description is thereby provided for electromagnetic-field propagation in general non-local and non-stationary dispersive and absorbing optical media, including a fundamental microscopic treatment of decoherence and relaxation processes due to environmental collisional and electromagnetic interactions. Particular interest is centered on entangled states and other non-classical states of electromagnetic fields, which may be created by non-linear electromagnetic interactions and detected by the measurement of various electromagnetic-field correlation functions. Accordingly, we present dynamical descriptions based on general forms of electromagnetic-field correlation functions involving both the electric-field and the magnetic-field components of the electromagnetic field, which are treated on an equal footing. Work supported by the Office of Naval Research through the Basic Research Program at The Naval Research Laboratory.

Non-canonical transcription initiation: the expanding universe of transcription initiating substrates.

PubMed

Barvík, Ivan; Rejman, Dominik; Panova, Natalya; Šanderová, Hana; Krásný, Libor

2017-03-01

RNA polymerase (RNAP) is the central enzyme of transcription of the genetic information from DNA into RNA. RNAP recognizes four main substrates: ATP, CTP, GTP and UTP. Experimental evidence from the past several years suggests that, besides these four NTPs, other molecules can be used to initiate transcription: (i) ribooligonucleotides (nanoRNAs) and (ii) coenzymes such as NAD+, NADH, dephospho-CoA and FAD. The presence of these molecules at the 5΄ ends of RNAs affects the properties of the RNA. Here, we discuss the expanding portfolio of molecules that can initiate transcription, their mechanism of incorporation, effects on RNA and cellular processes, and we present an outlook toward other possible initiation substrates. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Long-term Efficacy, Safety, and Immunogenicity of Biosimilar Infliximab After One Year in a Prospective Nationwide Cohort.

PubMed

Gonczi, Lorant; Gecse, Krisztina B; Vegh, Zsuzsanna; Kurti, Zsuzsanna; Rutka, Mariann; Farkas, Klaudia; Golovics, Petra A; Lovasz, Barbara D; Banai, Janos; Bene, Laszlo; Gasztonyi, Bea; Kristof, Tunde; Lakatos, Laszlo; Miheller, Pal; Nagy, Ferenc; Palatka, Karoly; Papp, Maria; Patai, Arpad; Salamon, Agnes; Szamosi, Tamas; Szepes, Zoltan; Toth, Gabor T; Vincze, Aron; Szalay, Balazs; Molnar, Tamas; Lakatos, Peter L

2017-11-01

It has been previously shown that biosimilar infliximab CT-P13 is effective and safe in inducing remission in inflammatory bowel diseases. We report here the 1-year outcomes from a prospective nationwide inflammatory bowel disease cohort. A prospective, nationwide, multicenter, observational cohort was designed to examine the efficacy and safety of CT-P13 in the induction and maintenance treatment of Crohn's disease (CD) and ulcerative colitis (UC). Demographic data were collected and a harmonized monitoring strategy was applied. Clinical remission, response, and biochemical response were evaluated at weeks 14, 30, and 54, respectively. Safety data were registered. Three hundred fifty-three consecutive inflammatory bowel disease (209 CD and 144 UC) patients were included, of which 229 patients reached the week 54 endpoint at final evaluation. Age at disease onset: 24/28 years (median, interquartile range: 19-34/22-39) in patients with CD/UC. Forty-nine, 53, 48% and 86, 81 and 65% of patients with CD reached clinical remission and response by weeks 14, 30, and 54, respectively. Clinical remission and response rates were 56, 41, 43% and 74, 66, 50% in patients with UC. Clinical efficacy was influenced by previous anti-tumor necrosis factor (TNF) exposure in patients with a drug holiday beyond 1 year. The mean C-reactive protein level decreased significantly in both CD and UC by week 14 and was maintained throughout the 1-year follow-up (both UC/CD: P < 0.001). Thirty-one (8.8%) patients had infusion reactions and 32 (9%) patients had infections. Antidrug antibody positivity rates were significantly higher throughout patients with previous anti-TNF exposure; concomitant azathioprine prevented antidrug antibody formation in anti-TNF-naive patients with CD. Results from this prospective nationwide cohort confirm that CT-P13 is effective and safe in inducing and maintaining long-term remission in both CD and UC. Efficacy was influenced by previous anti-TNF exposure; no new safety signals were detected.

Variability of Aerosol and its Impact on Cloud Properties Over Different Cities of Pakistan

NASA Astrophysics Data System (ADS)

Alam, Khan

Interaction between aerosols and clouds is the subject of considerable scientific research, due to the importance of clouds in controlling climate. Aerosols vary in time in space and can lead to variations in cloud microphysics. This paper is a pilot study to examine the temporal and spatial variation of aerosol particles and their impact on different cloud optical properties in the territory of Pakistan using the Moderate resolution Imaging Spectroradiometer (MODIS) on board NASA's Terra satellite data and Multi-angle Imaging Spectroradiometer (MISR) data. We also use Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model for trajectory analysis to obtain origin of air masses in order to understand the spatial and temporal variability of aerosol concentrations. We validate data of MODIS and MISR by using linear correlation and regression analysis, which shows that there is an excellent agreement between data of these instruments. Seasonal study of Aerosol Optical Depth (AOD) shows that maximum value is found in monsoon season (June-August) over all study areas. We analyze the relationships between aerosol optical depth (AOD) and some cloud parameters like water vapor (WV), cloud fraction (CF), cloud top temperature (CTT) and cloud top pressure (CTP). We construct the regional correlation maps and time series plots for aerosol and cloud parameters mandatory for the better understanding of aerosol-cloud interaction. Our analyses show that there is a strong positive correlation between AOD and water vapor in all cities. The correlation between AOD and CF is positive for the cities where the air masses are moist while the correlation is negative for cities where air masses are relatively dry and with lower aerosol abundance. It shows that these correlations depend on meteorological conditions. Similarly as AOD increases Cloud Top Pressure (CTP) is decreasing while Cloud Top Temperature (CTT) is increasing. Key Words: MODIS, MISR, HYSPLIT, AOD, CF, CTP, CTT

A comparison of Aqua MODIS ice and liquid water cloud physical and optical properties between collection 6 and collection 5.1: Pixel-to-pixel comparisons

NASA Astrophysics Data System (ADS)

Yi, Bingqi; Rapp, Anita D.; Yang, Ping; Baum, Bryan A.; King, Michael D.

2017-04-01

We compare differences in ice and liquid water cloud physical and optical properties between Aqua Moderate Resolution Imaging Spectroradiometer (MODIS) collection 6 (C6) and collection 5.1 (C51). The C6 cloud products changed significantly due to improved calibration, improvements based on comparisons with the Cloud-Aerosol Lidar with Orthogonal Polarization, treatment of subpixel liquid water clouds, introduction of a roughened ice habit for C6 rather than the use of smooth ice particles in C51, and more. The MODIS cloud products form a long-term data set for analysis, modeling, and various purposes. Thus, it is important to understand the impact of the changes. Two cases are considered for C6 to C51 comparisons. Case 1 considers pixels with valid cloud retrievals in both C6 and C51, while case 2 compares all valid cloud retrievals in each collection. One year (2012) of level-2 MODIS cloud products are examined, including cloud effective radius (CER), optical thickness (COT), water path, cloud top pressure (CTP), cloud top temperature, and cloud fraction. Large C6-C51 differences are found in the ice CER (regionally, as large as 15 μm) and COT (decrease in annual average by approximately 25%). Liquid water clouds have higher CTP in marine stratocumulus regions in C6 but lower CTP globally (-5 hPa), and there are 66% more valid pixels in C6 (case 2) due to the treatment of pixels with subpixel clouds. Simulated total cloud radiative signatures from C51 and C6 are compared to Clouds and the Earth's Radiant Energy System Energy Balanced And Filled (EBAF) product. The C6 CREs compare more closely with the EBAF than the C51 counterparts.

Predictors of hospital re-admissions among Hispanics with hepatitis C-related cirrhosis

PubMed Central

Atla, Pradeep R.; Sheikh, Muhammad Y.; Gill, Firdose; Kundu, Rabindra; Choudhury, Jayanta

2016-01-01

Background Hospital re-admissions in decompensated cirrhosis are associated with worse patient outcomes. Hispanics have a disproportionately high prevalence of hepatitis C virus (HCV)-related morbidity and mortality. The goal of this study was to evaluate the factors affecting re-admission rates among Hispanics with HCV-related cirrhosis. Methods A total of 292 consecutive HCV-related cirrhosis admissions (Hispanics 189, non-Hispanics 103) from January 2009 to December 2012 were retrospectively reviewed; 132 were cirrhosis-related re-admissions. The statistical analysis was performed using STATA version 11.1. Chi-square/Fisher’s exact and Student’s t-tests were used to compare categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to identify predictors for hospital readmissions. Results Among the 132 cirrhosis-related readmissions, 71% were Hispanics while 29% were non-Hispanics (P=0.035). Hepatic encephalopathy (HE) and esophageal variceal hemorrhage were the most frequent causes of the first and subsequent readmissions. Hispanics with readmissions had a higher Child-Turcotte-Pugh (CTP) class (B and C) and higher model for end-stage liver disease (MELD) scores (≥15), as well as a higher incidence of alcohol use, HE, spontaneous bacterial peritonitis, hepatocellular carcinoma, and varices (P<0.05). The majority of the study patients (81%) had MELD scores <15. Multivariate regression analysis identified alcohol use (OR 2.63; 95%CI 1.1-6.4), HE (OR 5.5; 95%CI 2-15.3), varices (OR 3.2; 95%CI 1.3-8.2), and CTP class (OR 3.3; 95%CI 1.4–8.1) as predictors for readmissions among Hispanics. Conclusion CTP classes B and C, among other factors, were the major predictors for hospital readmissions in Hispanics with HCV-related cirrhosis. The majority of these readmissions were due to HE and variceal hemorrhage. PMID:27708520

Electromagnetic Imaging Methods for Nondestructive Evaluation Applications

PubMed Central

Deng, Yiming; Liu, Xin

2011-01-01

Electromagnetic nondestructive tests are important and widely used within the field of nondestructive evaluation (NDE). The recent advances in sensing technology, hardware and software development dedicated to imaging and image processing, and material sciences have greatly expanded the application fields, sophisticated the systems design and made the potential of electromagnetic NDE imaging seemingly unlimited. This review provides a comprehensive summary of research works on electromagnetic imaging methods for NDE applications, followed by the summary and discussions on future directions. PMID:22247693

Hybrid Contactless Heating and Levitation

NASA Technical Reports Server (NTRS)

Lee, M. C.

1985-01-01

Acoustic and electromagnetic fields applied. In contactless processing apparatus, acoustic and electromagnetic levitating fields employed alternately or simultaneously with amplitude of each controlled to produce various combinations of heating, cooling, and levitation. Apparatus provides rapid heating and cooling or slow heating and cooling for such processes as nucleation, crystallization, incubation, deep undercooling, and heterogeneity control.

Biochemical and Physical Properties of the Methanococcus jannaschii 20S Proteasome and PAN, a Homolog of the ATPase (Rpt) Subunits of the Eucaryal 26S Proteasome†

PubMed Central

Wilson, Heather L.; Ou, Mark S.; Aldrich, Henry C.; Maupin-Furlow, Julie

2000-01-01

The 20S proteasome is a self-compartmentalized protease which degrades unfolded polypeptides and has been purified from eucaryotes, gram-positive actinomycetes, and archaea. Energy-dependent complexes, such as the 19S cap of the eucaryal 26S proteasome, are assumed to be responsible for the recognition and/or unfolding of substrate proteins which are then translocated into the central chamber of the 20S proteasome and hydrolyzed to polypeptide products of 3 to 30 residues. All archaeal genomes which have been sequenced are predicted to encode proteins with up to ∼50% identity to the six ATPase subunits of the 19S cap. In this study, one of these archaeal homologs which has been named PAN for proteasome-activating nucleotidase was characterized from the hyperthermophile Methanococcus jannaschii. In addition, the M. jannaschii 20S proteasome was purified as a 700-kDa complex by in vitro assembly of the α and β subunits and has an unusually high rate of peptide and unfolded-polypeptide hydrolysis at 100°C. The 550-kDa PAN complex was required for CTP- or ATP-dependent degradation of β-casein by archaeal 20S proteasomes. A 500-kDa complex of PAN(Δ1–73), which has a deletion of residues 1 to 73 of the deduced protein and disrupts the predicted N-terminal coiled-coil, also facilitated this energy-dependent proteolysis. However, this deletion increased the types of nucleotides hydrolyzed to include not only ATP and CTP but also ITP, GTP, TTP, and UTP. The temperature optimum for nucleotide (ATP) hydrolysis was reduced from 80°C for the full-length protein to 65°C for PAN(Δ1–73). Both PAN protein complexes were stable in the absence of ATP and were inhibited by N-ethylmaleimide and p-chloromercuriphenyl-sulfonic acid. Kinetic analysis reveals that the PAN protein has a relatively high Vmax for ATP and CTP hydrolysis of 3.5 and 5.8 μmol of Pi per min per mg of protein as well as a relatively low affinity for CTP and ATP with Km values of 307 and 497 μM compared to other proteins of the AAA family. Based on electron micrographs, PAN and PAN(Δ1–73) apparently associate with the ends of the 20S proteasome cylinder. These results suggest that the M. jannaschii as well as related archaeal 20S proteasomes require a nucleotidase complex such as PAN to mediate the energy-dependent hydrolysis of folded-substrate proteins and that the N-terminal 73 amino acid residues of PAN are not absolutely required for this reaction. PMID:10692374

Footwear scanning systems and methods

DOEpatents

Fernandes, Justin L.; McMakin, Douglas L.; Sheen, David M.; Tedeschi, Jonathan R.

2017-07-25

Methods and apparatus for scanning articles, such as footwear, to provide information regarding the contents of the articles are described. According to one aspect, a footwear scanning system includes a platform configured to contact footwear to be scanned, an antenna array configured to transmit electromagnetic waves through the platform into the footwear and to receive electromagnetic waves from the footwear and the platform, a transceiver coupled with antennas of the antenna array and configured to apply electrical signals to at least one of the antennas to generate the transmitted electromagnetic waves and to receive electrical signals from at least another of the antennas corresponding to the electromagnetic waves received by the others of the antennas, and processing circuitry configured to process the received electrical signals from the transceiver to provide information regarding contents within the footwear.

Study on electromagnetic radiation and mechanical characteristics of coal during an SHPB test

NASA Astrophysics Data System (ADS)

Chengwu, Li; Qifei, Wang; Pingyang, Lyu

2016-06-01

Dynamic loads provided by a Split Hopkinson pressure bar are applied in the impact failure experiment on coal with an impact velocity of 4.174-17.652 m s-1. The mechanical property characteristics of coal and an electromagnetic radiation signal can be detected and measured during the experiment. The variation of coal stress, strain, incident energy, dissipated energy and other mechanical parameters are analyzed by the unidimensional stress wave theory. It suggests that with an increase of the impact velocity, the mechanical parameters and electromagnetic radiation increased significantly and the dissipated energy of the coal sample has a high discrete growing trend during the failure process of coal impact. Combined with the received energy of the electromagnetic radiation signal, the relationship between these mechanical parameters and electromagnetic radiation during the failure process of coal burst could be analyzed by the grey correlation model. The results show that the descending order of the gray correlation degree between the mechanical characteristics and electromagnetic radiation energy are impact velocity, maximum stress, the average stress, incident energy, the average strain, maximum strain, the average strain rate and dissipation energy. Due to the correlation degree, the impact velocity and incident energy are relatively large, and the main factor affecting the electromagnetic radiation energy of coal is the energy magnitude. While the relationship between extreme stress and the radiation energy change trend is closed, the stress state of coal has a greater impact on electromagnetic radiation than the strain and destruction which can deepen the research of the coal-rock dynamic disaster electromagnetic monitoring technique.

Real-time wideband cylindrical holographic surveillance system

DOEpatents

Sheen, David M.; McMakin, Douglas L.; Hall, Thomas E.; Severtsen, Ronald H.

1999-01-01

A wideband holographic cylindrical surveillance system including a transceiver for generating a plurality of electromagnetic waves; antenna for transmitting the electromagnetic waves toward a target at a plurality of predetermined positions in space; the transceiver also receiving and converting electromagnetic waves reflected from the target to electrical signals at a plurality of predetermined positions in space; a computer for processing the electrical signals to obtain signals corresponding to a holographic reconstruction of the target; and a display for displaying the processed information to determine nature of the target. The computer has instructions to apply Fast Fourier Transforms and obtain a three dimensional cylindrical image.

Real-time wideband holographic surveillance system

DOEpatents

Sheen, David M.; Collins, H. Dale; Hall, Thomas E.; McMakin, Douglas L.; Gribble, R. Parks; Severtsen, Ronald H.; Prince, James M.; Reid, Larry D.

1996-01-01

A wideband holographic surveillance system including a transceiver for generating a plurality of electromagnetic waves; antenna for transmitting the electromagnetic waves toward a target at a plurality of predetermined positions in space; the transceiver also receiving and converting electromagnetic waves reflected from the target to electrical signals at a plurality of predetermined positions in space; a computer for processing the electrical signals to obtain signals corresponding to a holographic reconstruction of the target; and a display for displaying the processed information to determine nature of the target. The computer has instructions to apply a three dimensional backward wave algorithm.

Real-time wideband holographic surveillance system

DOEpatents

Sheen, D.M.; Collins, H.D.; Hall, T.E.; McMakin, D.L.; Gribble, R.P.; Severtsen, R.H.; Prince, J.M.; Reid, L.D.

1996-09-17

A wideband holographic surveillance system including a transceiver for generating a plurality of electromagnetic waves; antenna for transmitting the electromagnetic waves toward a target at a plurality of predetermined positions in space; the transceiver also receiving and converting electromagnetic waves reflected from the target to electrical signals at a plurality of predetermined positions in space; a computer for processing the electrical signals to obtain signals corresponding to a holographic reconstruction of the target; and a display for displaying the processed information to determine nature of the target. The computer has instructions to apply a three dimensional backward wave algorithm. 28 figs.

Sparsity Aware Adaptive Radar Sensor Imaging in Complex Scattering Environments

DTIC Science & Technology

2015-06-15

while meeting the requirement on the peak to average power ratio. Third, we study impact of waveform encoding on nonlinear electromagnetic tomographic...Enyue Lu. Time Domain Electromagnetic Tomography Using Propagation and Backpropagation Method, IEEE International Conference on Image Processing...Received Paper 3.00 4.00 Yuanwei Jin, Chengdon Dong, Enyue Lu. Waveform Encoding for Nonlinear Electromagnetic Tomographic Imaging, IEEE Global

Research on Radiation Characteristic of Plasma Antenna through FDTD Method

PubMed Central

Zhou, Jianming; Fang, Jingjing; Lu, Qiuyuan; Liu, Fan

2014-01-01

The radiation characteristic of plasma antenna is investigated by using the finite-difference time-domain (FDTD) approach in this paper. Through using FDTD method, we study the propagation of electromagnetic wave in free space in stretched coordinate. And the iterative equations of Maxwell equation are derived. In order to validate the correctness of this method, we simulate the process of electromagnetic wave propagating in free space. Results show that electromagnetic wave spreads out around the signal source and can be absorbed by the perfectly matched layer (PML). Otherwise, we study the propagation of electromagnetic wave in plasma by using the Boltzmann-Maxwell theory. In order to verify this theory, the whole process of electromagnetic wave propagating in plasma under one-dimension case is simulated. Results show that Boltzmann-Maxwell theory can be used to explain the phenomenon of electromagnetic wave propagating in plasma. Finally, the two-dimensional simulation model of plasma antenna is established under the cylindrical coordinate. And the near-field and far-field radiation pattern of plasma antenna are obtained. The experiments show that the variation of electron density can introduce the change of radiation characteristic. PMID:25114961

Experimental research of the influence of the strength of ore samples on the parameters of an electromagnetic signal during acoustic excitation in the process of uniaxial compression

NASA Astrophysics Data System (ADS)

Yavorovich, L. V.; Bespal`ko, A. A.; Fedotov, P. I.

2018-01-01

Parameters of electromagnetic responses (EMRe) generated during uniaxial compression of rock samples under excitation by deterministic acoustic pulses are presented and discussed. Such physical modeling in the laboratory allows to reveal the main regularities of electromagnetic signals (EMS) generation in rock massive. The influence of the samples mechanical properties on the parameters of the EMRe excited by an acoustic signal in the process of uniaxial compression is considered. It has been established that sulfides and quartz in the rocks of the Tashtagol iron ore deposit (Western Siberia, Russia) contribute to the conversion of mechanical energy into the energy of the electromagnetic field, which is expressed in an increase in the EMS amplitude. The decrease in the EMS amplitude when the stress-strain state of the sample changes during the uniaxial compression is observed when the amount of conductive magnetite contained in the rock is increased. The obtained results are important for the physical substantiation of testing methods and monitoring of changes in the stress-strain state of the rock massive by the parameters of electromagnetic signals and the characteristics of electromagnetic emission.

Update of the SEPD position statement on the use of biosimilars for inflammatory bowel disease.

PubMed

Argüelles Arias, Federico; Hinojosa Del Val, Joaquín; Vera Mendoza, Isabel

2018-03-12

In 2013, the European Medicines Agency (EMA) approved the biosimilar infliximab (CT-P13) for the full range of indications of the originator product, based on data from two trials conducted in rheumatoid arthritis and ankylosing spondylitis. The same year, our Society published a position statement that was later reviewed.

In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products: Workshop Proceedings, Conclusions, and Paths Forward for In Vitro Model Use

EPA Science Inventory

In 2009, the passing of The Family Smoking Prevention and Tobacco Control Act facilitated the establishment of the FDA Center for Tobacco Products (CTP) and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed “...

Electromagnetic Dissociation of Uranium in Heavy Ion Collisions at 120 Mev/a

NASA Astrophysics Data System (ADS)

Justice, Marvin Lealon

The heavy-ion induced electromagnetic dissociation (EMD) of a 120 MeV/A ^{238}U beam incident on five targets (^9Be, ^{27}Al, ^ {nat}Cu, ^{nat} Ag, and ^{nat}U) has been studied experimentally. Electromagnetic dissociation at this beam energy is essentially a two step process involving the excitation of a giant resonance followed by particle decay. At 120 MeV/A there is predicted to be a significant contribution (~25%) of the giant quadrupole resonance to the EMD cross sections. The specific exit channel which was looked at was projectile fission. The two fission fragments were detected in coincidence by an array of solid-state DeltaE-E detectors, allowing the charges of the fragments to be determined to within +/- .5 units. The events were sorted on the basis of the sums of the fragments' charges, acceptance corrections were applied, and total cross sections for the most peripheral events (i.e. those leading to charge sums of approximately 92) were determined. Electromagnetic fission at the beam energy of this experiment always leads to a true charge sum of 92. Due to the imperfect resolution of the detectors, charge sums of 91 and 93 were included in order to account for all of the electromagnetic fission events. The experimentally observed cross sections are due to nuclear interaction processes as well as electromagnetic processes. Under the conditions of this experiment, the cross sections for the beryllium target are almost entirely due to nuclear processes. The nuclear cross sections for the other four targets were determined by extrapolation from the beryllium data using a geometrical scaling model. After subtraction of the nuclear cross sections, the resulting electromagnetic cross sections are compared to theoretical calculations based on the equivalent photon approximation. Systematic uncertainties associated with the normalization of the data make quantitative comparisons with theory difficult, however. The systematic uncertainties are discussed and suggestions for improving the experiment are given.

Electromagnetic cellular interactions.

PubMed

Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

2011-05-01

Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating. Copyright © 2010 Elsevier Ltd. All rights reserved.

Processing Waveform-Based NDE

NASA Technical Reports Server (NTRS)

Roth, Donald J (Inventor)

2011-01-01

A computer implemented process for simultaneously measuring the velocity of terahertz electromagnetic radiation in a dielectric material sample without prior knowledge of the thickness of the sample and for measuring the thickness of a material sample using terahertz electromagnetic radiation in a material sample without prior knowledge of the velocity of the terahertz electromagnetic radiation in the sample is disclosed and claimed. Utilizing interactive software the process evaluates, in a plurality of locations, the sample for microstructural variations and for thickness variations and maps the microstructural and thickness variations by location. A thin sheet of dielectric material may be used on top of the sample to create a dielectric mismatch. The approximate focal point of the radiation source (transceiver) is initially determined for good measurements.

Large space structures fabrication experiment. [on-orbit fabrication of graphite/thermoplastic beams

NASA Technical Reports Server (NTRS)

1978-01-01

The fabrication machine used for the rolltrusion and on-orbit forming of graphite thermoplastic (CTP) strip material into structural sections is described. The basic process was analytically developed parallel with, and integrated into the conceptual design of, a flight experiment machine for producing a continuous triangular cross section truss. The machine and its associated ancillary equipment are mounted on a Space Lab pallet. Power, thermal control, and instrumentation connections are made during ground installation. Observation, monitoring, caution and warning, and control panels and displays are installed at the payload specialist station in the orbiter. The machine is primed before flight by initiation of beam forming, to include attachment of the first set of cross members and anchoring of the diagonal cords. Control of the experiment will be from the orbiter mission specialist station. Normal operation is by automatic processing control software. Machine operating data are displayed and recorded on the ground. Data is processed and formatted to show progress of the major experiment parameters including stable operation, physical symmetry, joint integrity, and structural properties.

Organo luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes

DOEpatents

Weiss, Shimon [Pinole, CA; Bruchez, Jr., Marcel; Alivisatos, Paul [Oakland, CA

2008-01-01

A semiconductor nanocrystal compound is described capable of linking to an affinity molecule. The compound comprises (1) a semiconductor nanocrystal capable of emitting electromagnetic radiation and/or absorbing energy, and/or scattering or diffracting electromagnetic radiation--when excited by an electromagnetic radiation source or a particle beam; and (2) an affinity molecule linked to the semiconductor nanocrystal. The semiconductor nanocrystal is linked to an affinity molecule to form a semiconductor nanocrystal probe capable of bonding with a detectable substance. Exposure of the semiconductor nanocrystal to excitation energy will excite the semiconductor nanocrystal causing the emission of electromagnetic radiation. Further described are processes for respectively: making the luminescent semiconductor nanocrystal compound; making the semiconductor nanocrystal probe; and using the probe to determine the presence of a detectable substance in a material.

Spontaneous ultraweak photon emission from biological systems and the endogenous light field.

PubMed

Schwabl, Herbert; Klima, Herbert

2005-04-01

Still one of the most astonishing biological electromagnetic phenomena is the ultraweak photon emission (UPE) from living systems. Organisms and tissues spontaneously emit measurable intensities of light, i.e. photons in the visible part of the electromagnetic spectrum (380-780 nm), in the range from 1 to 1,000 photons x s-1 x cm-2, depending on their condition and vitality. It is important not to confuse UPE from living systems with other biogenic light emitting processes such as bioluminescence or chemiluminescence. This article examines with basic considerations from physics on the quantum nature of photons the empirical phenomenon of UPE. This leads to the description of the non-thermal origin of this radiation. This is in good correspondence with the modern understanding of life phenomena as dissipative processes far from thermodynamic equilibrium. UPE also supports the understanding of life sustaining processes as basically driven by electromagnetic fields. The basic features of UPE, like intensity and spectral distribution, are known in principle for many experimental situations. The UPE of human leukocytes contributes to an endogenous light field of about 1011 photons x s-1 which can be influenced by certain factors. Further research is needed to reveal the statistical properties of UPE and in consequence to answer questions about the underlying mechanics of the biological system. In principle, statistical properties of UPE allow to reconstruct phase-space dynamics of the light emitting structures. Many open questions remain until a proper understanding of the electromagnetic interaction of the human organism can be achieved: which structures act as receptors and emitters for electromagnetic radiation? How is electromagnetic information received and processed within cells?

Broadband electromagnetic analysis of compacted kaolin

NASA Astrophysics Data System (ADS)

Bore, Thierry; Wagner, Norman; Cai, Caifang; Scheuermann, Alexander

2017-01-01

The mechanical compaction of soil influences not only the mechanical strength and compressibility but also the hydraulic behavior in terms of hydraulic conductivity and soil suction. At the same time, electric and dielectric parameters are increasingly used to characterize soil and to relate them with mechanic and hydraulic parameters. In the presented study electromagnetic soil properties and suction were measured under defined conditions of standardized compaction tests. The impact of external mechanical stress conditions of nearly pure kaolinite was analyzed on soil suction and broadband electromagnetic soil properties. An experimental procedure was developed and validated to simultaneously determine mechanical, hydraulic and broadband (1 MHz-3 GHz) electromagnetic properties of the porous material. The frequency dependent electromagnetic properties were modeled with a classical mixture equation (advanced Lichtenecker and Rother model, ALRM) and a hydraulic-mechanical-electromagnetic coupling approach was introduced considering water saturation, soil structure (bulk density, porosity), soil suction (pore size distribution, water sorption) as well as electrical conductivity of the aqueous pore solution. Moreover, the relaxation behavior was analyzed with a generalized fractional relaxation model concerning a high-frequency water process and two interface processes extended with an apparent direct current conductivity contribution. The different modeling approaches provide a satisfactory agreement with experimental data for the real part. These results show the potential of broadband electromagnetic approaches for quantitative estimation of the hydraulic state of the soil during densification.

Influence of Spectral Transfer Processes in Compressible Low Frequency Plasma Turbulence on Scattering and Refraction of Electromagnetic Signals

DTIC Science & Technology

2015-01-01

AFRL-RY-WP-TR-2014-0230 INFLUENCE OF SPECTRAL TRANSFER PROCESSES IN COMPRESSIBLE LOW FREQUENCY PLASMA TURBULENCE ON SCATTERING AND...INFLUENCE OF SPECTRAL TRANSFER PROCESSES IN COMPRESSIBLE LOW FREQUENCY PLASMA TURBULENCE ON SCATTERING AND REFRACTION OF ELECTROMAGNETIC SIGNALS 5a...research is to analyze influence of plasma turbulence on hypersonic sensor systems and NGOTHR applications and to meet the Air Force’s ever-increasing

Electromagnetic Components of Auroral Hiss and Lower Hybrid Waves in the Polar Magnetosphere

NASA Technical Reports Server (NTRS)

Wong, H. K.

1995-01-01

DE-1 has frequently observed waves in the whistler and lower hybrid frequencies range. Besides the electrostatic components, these waves also exhibit electromagnetic components. It is generally believed that these waves are excited by the electron acoustic instability and the electron-beam-driven lower hybrid instability. Because the electron acoustic and the lower hybrid waves are predominately electrostatic waves, they cannot account for the observed electromagnetic components. In this work, it is suggested that these electromagnetic components can be explained by waves that are generated near the resonance cone and that propagate away from the source. The role that these electromagnetic waves can play in particle acceleration processes at low altitude is discussed.

Microwave thawing package and method

DOEpatents

Fathi, Zakaryae; Lauf, Robert J.

2004-03-16

A package for containing frozen liquids during an electromagnetic thawing process includes: a first section adapted for containing a frozen material and exposing the frozen material to electromagnetic energy; a second section adapted for receiving thawed liquid material and shielding the thawed liquid material from further exposure to electromagnetic energy; and a fluid communication means for allowing fluid flow between the first section and the second section.

Electrical wire insulation and electromagnetic coil

DOEpatents

Bich, George J.; Gupta, Tapan K.

1984-01-01

An electromagnetic coil for high temperature and high radiation application in which glass is used to insulate the electrical wire. A process for applying the insulation to the wire is disclosed which results in improved insulation properties.

An application of LOTEM around salt dome near Houston, Texas

NASA Astrophysics Data System (ADS)

Paembonan, Andri Yadi; Arjwech, Rungroj; Davydycheva, Sofia; Smirnov, Maxim; Strack, Kurt M.

2017-07-01

A salt dome is an important large geologic structure for hydrocarbon exploration. It may seal a porous reservoir of rocks that form petroleum reservoirs. Several techniques such as seismic, gravity, and electromagnetic including magnetotelluric have successfully yielded salt dome interpretation. Seismic has difficulties seeing through the salt because the seismic energy gets trapped by the salt due to its high velocity. Gravity and electromagnetics are more ideal methods. Long Offset Transient Electromagnetic (LOTEM) and Focused Source Electromagnetic (FSEM) were tested over a salt dome near Houston, Texas. LOTEM data were recorded at several stations with varying offset, and the FSEM tests were also made at some receiver locations near a suspected salt overhang. The data were processed using KMS's processing software: First, for assurance, including calibration and header checking; then transmitter and receiver data are merged and microseismic data is separated; Finally, data analysis and processing follows. LOTEM processing leads to inversion or in the FSEM case 3D modeling. Various 3D models verify the sensitivity under the salt dome. In addition, the processing was conducted pre-stack, stack, and post-stack. After pre-stacking, the noise was reduced, but showed the ringing effect due to a low-pass filter. Stacking and post-stacking with applying recursive average could reduce the Gibbs effect and produce smooth data.

Real-time wideband cylindrical holographic surveillance system

DOEpatents

Sheen, D.M.; McMakin, D.L.; Hall, T.E.; Severtsen, R.H.

1999-01-12

A wideband holographic cylindrical surveillance system is disclosed including a transceiver for generating a plurality of electromagnetic waves; antenna for transmitting the electromagnetic waves toward a target at a plurality of predetermined positions in space; the transceiver also receiving and converting electromagnetic waves reflected from the target to electrical signals at a plurality of predetermined positions in space; a computer for processing the electrical signals to obtain signals corresponding to a holographic reconstruction of the target; and a display for displaying the processed information to determine nature of the target. The computer has instructions to apply Fast Fourier Transforms and obtain a three dimensional cylindrical image. 13 figs.

A Review of Low Frequency Electromagnetic Wave Phenomena Related to Tropospheric-Ionospheric Coupling Mechanisms

NASA Technical Reports Server (NTRS)

Simoes, Fernando; Pfaff, Robert; Berthelier, Jean-Jacques; Klenzing, Jeffrey

2012-01-01

Investigation of coupling mechanisms between the troposphere and the ionosphere requires a multidisciplinary approach involving several branches of atmospheric sciences, from meteorology, atmospheric chemistry, and fulminology to aeronomy, plasma physics, and space weather. In this work, we review low frequency electromagnetic wave propagation in the Earth-ionosphere cavity from a troposphere-ionosphere coupling perspective. We discuss electromagnetic wave generation, propagation, and resonance phenomena, considering atmospheric, ionospheric and magnetospheric sources, from lightning and transient luminous events at low altitude to Alfven waves and particle precipitation related to solar and magnetospheric processes. We review in situ ionospheric processes as well as surface and space weather phenomena that drive troposphere-ionosphere dynamics. Effects of aerosols, water vapor distribution, thermodynamic parameters, and cloud charge separation and electrification processes on atmospheric electricity and electromagnetic waves are reviewed. We also briefly revisit ionospheric irregularities such as spread-F and explosive spread-F, sporadic-E, traveling ionospheric disturbances, Trimpi effect, and hiss and plasma turbulence. Regarding the role of the lower boundary of the cavity, we review transient surface phenomena, including seismic activity, earthquakes, volcanic processes and dust electrification. The role of surface and atmospheric gravity waves in ionospheric dynamics is also briefly addressed. We summarize analytical and numerical tools and techniques to model low frequency electromagnetic wave propagation and solving inverse problems and summarize in a final section a few challenging subjects that are important for a better understanding of tropospheric-ionospheric coupling mechanisms.

Intraluminal laser atherectomy with ultrasound and electromagnetic guidance

NASA Astrophysics Data System (ADS)

Gregory, Kenton W.; Aretz, H. Thomas; Martinelli, Michael A.; LeDet, Earl G.; Hatch, G. F.; Gregg, Richard E.; Sedlacek, Tomas; Haase, Wayne C.

1991-05-01

The MagellanTM coronary laser atherectomy system is described. It uses high- resolution ultrasound imaging and electromagnetic sensing to provide real-time guidance and control of laser therapy in the coronary arteries. The system consists of a flexible catheter, an electromagnetic navigation antenna, a sensor signal processor and a computer for image processing and display. The small, flexible catheter combines an ultrasound transducer and laser delivery optics, aimed at the artery wall, and an electromagnetic receiving sensor. An extra-corporeal electromagnetic transmit antenna, in combination with catheter sensors, locates the position of the ultrasound and laser beams in the artery. Navigation and ultrasound data are processed electronically to produce real-time, transverse, and axial cross-section images of the artery wall at selected locations. By exploiting the ability of ultrasound to image beneath the surface of artery walls, it is possible to identify candidate treatment sites and perform safe radial laser debulking of atherosclerotic plaque with reduced danger of perforation. The utility of the system in plaque identification and ablation is demonstrated with imaging and experimental results.

An Attachable Electromagnetic Energy Harvester Driven Wireless Sensing System Demonstrating Milling-Processes and Cutter-Wear/Breakage-Condition Monitoring.

PubMed

Chung, Tien-Kan; Yeh, Po-Chen; Lee, Hao; Lin, Cheng-Mao; Tseng, Chia-Yung; Lo, Wen-Tuan; Wang, Chieh-Min; Wang, Wen-Chin; Tu, Chi-Jen; Tasi, Pei-Yuan; Chang, Jui-Wen

2016-02-23

An attachable electromagnetic-energy-harvester driven wireless vibration-sensing system for monitoring milling-processes and cutter-wear/breakage-conditions is demonstrated. The system includes an electromagnetic energy harvester, three single-axis Micro Electro-Mechanical Systems (MEMS) accelerometers, a wireless chip module, and corresponding circuits. The harvester consisting of magnets with a coil uses electromagnetic induction to harness mechanical energy produced by the rotating spindle in milling processes and consequently convert the harnessed energy to electrical output. The electrical output is rectified by the rectification circuit to power the accelerometers and wireless chip module. The harvester, circuits, accelerometer, and wireless chip are integrated as an energy-harvester driven wireless vibration-sensing system. Therefore, this completes a self-powered wireless vibration sensing system. For system testing, a numerical-controlled machining tool with various milling processes is used. According to the test results, the system is fully self-powered and able to successfully sense vibration in the milling processes. Furthermore, by analyzing the vibration signals (i.e., through analyzing the electrical outputs of the accelerometers), criteria are successfully established for the system for real-time accurate simulations of the milling-processes and cutter-conditions (such as cutter-wear conditions and cutter-breaking occurrence). Due to these results, our approach can be applied to most milling and other machining machines in factories to realize more smart machining technologies.

An Attachable Electromagnetic Energy Harvester Driven Wireless Sensing System Demonstrating Milling-Processes and Cutter-Wear/Breakage-Condition Monitoring

PubMed Central

Chung, Tien-Kan; Yeh, Po-Chen; Lee, Hao; Lin, Cheng-Mao; Tseng, Chia-Yung; Lo, Wen-Tuan; Wang, Chieh-Min; Wang, Wen-Chin; Tu, Chi-Jen; Tasi, Pei-Yuan; Chang, Jui-Wen

2016-01-01

An attachable electromagnetic-energy-harvester driven wireless vibration-sensing system for monitoring milling-processes and cutter-wear/breakage-conditions is demonstrated. The system includes an electromagnetic energy harvester, three single-axis Micro Electro-Mechanical Systems (MEMS) accelerometers, a wireless chip module, and corresponding circuits. The harvester consisting of magnets with a coil uses electromagnetic induction to harness mechanical energy produced by the rotating spindle in milling processes and consequently convert the harnessed energy to electrical output. The electrical output is rectified by the rectification circuit to power the accelerometers and wireless chip module. The harvester, circuits, accelerometer, and wireless chip are integrated as an energy-harvester driven wireless vibration-sensing system. Therefore, this completes a self-powered wireless vibration sensing system. For system testing, a numerical-controlled machining tool with various milling processes is used. According to the test results, the system is fully self-powered and able to successfully sense vibration in the milling processes. Furthermore, by analyzing the vibration signals (i.e., through analyzing the electrical outputs of the accelerometers), criteria are successfully established for the system for real-time accurate simulations of the milling-processes and cutter-conditions (such as cutter-wear conditions and cutter-breaking occurrence). Due to these results, our approach can be applied to most milling and other machining machines in factories to realize more smart machining technologies. PMID:26907297

PROPOSED PROCEDURE FOR DERIVATION OF REGULATORY VALUES FOR CARCINOGENIC AIRBORNE POLYCYCLIC AROMATIC HYDROCARBONS (PAHS) BASED ON COAL TAR PITCH (CTP) VOLATILES

EPA Science Inventory

A procedure for estimating upper bound lifetime human cancer risk from air levels of 6 common carcinogenic PAHs, termed "PAHs of concern", is proposed. These PAHs are benzo(a)pyrene, benz(a)anathracene, benzo(k)flouranthene, indeno(1,2,3-c,d)pyrene and chrysene. In application,...

46 CFR Table I to Part 150 - Alphabetical List of Cargoes

Code of Federal Regulations, 2014 CFR

2014-10-01

... (C17+) alkanoic acid 34 CUS CFT Corn syrup 43 CSY Cottonseed oil, fatty acid 34 CFY Creosote 21 2 CCT... tar 33 COR OCT Coal tar distillate 33 CDL Coal tar, high temperature 33 CHH Coal tar pitch 33 CTP... MTM Formaldehyde solution 19 2 FMS Formamide 10 FAM Formic acid 4 2 FMA Fructose solution 43 Fumaric...

46 CFR Table I to Part 150 - Alphabetical List of Cargoes

Code of Federal Regulations, 2013 CFR

2013-10-01

... (C17+) alkanoic acid 34 CUS CFT Corn syrup 43 CSY Cottonseed oil, fatty acid 34 CFY Creosote 21 2 CCT... tar 33 COR OCT Coal tar distillate 33 CDL Coal tar, high temperature 33 CHH Coal tar pitch 33 CTP... MTM Formaldehyde solution 19 2 FMS Formamide 10 FAM Formic acid 4 2 FMA Fructose solution 43 Fumaric...

46 CFR Table I to Part 150 - Alphabetical List of Cargoes

Code of Federal Regulations, 2010 CFR

2010-10-01

... (C17+) alkanoic acid 34 CUS CFT Corn syrup 43 CSY Cottonseed oil, fatty acid 34 CFY Creosote 21 2 CCT... tar 33 COR OCT Coal tar distillate 33 CDL Coal tar, high temperature 33 CHH Coal tar pitch 33 CTP... MTM Formaldehyde solution 19 2 FMS Formamide 10 FAM Formic acid 4 2 FMA Fructose solution 43 Fumaric...

46 CFR Table I to Part 150 - Alphabetical List of Cargoes

Code of Federal Regulations, 2011 CFR

2011-10-01

... (C17+) alkanoic acid 34 CUS CFT Corn syrup 43 CSY Cottonseed oil, fatty acid 34 CFY Creosote 21 2 CCT... tar 33 COR OCT Coal tar distillate 33 CDL Coal tar, high temperature 33 CHH Coal tar pitch 33 CTP... MTM Formaldehyde solution 19 2 FMS Formamide 10 FAM Formic acid 4 2 FMA Fructose solution 43 Fumaric...

46 CFR Table I to Part 150 - Alphabetical List of Cargoes

Code of Federal Regulations, 2012 CFR

2012-10-01

... (C17+) alkanoic acid 34 CUS CFT Corn syrup 43 CSY Cottonseed oil, fatty acid 34 CFY Creosote 21 2 CCT... tar 33 COR OCT Coal tar distillate 33 CDL Coal tar, high temperature 33 CHH Coal tar pitch 33 CTP... MTM Formaldehyde solution 19 2 FMS Formamide 10 FAM Formic acid 4 2 FMA Fructose solution 43 Fumaric...

Semi-annual conference review January-June 2000

Treesearch

John K. Borchardt; Marguerite S. Sykes; Mahendra R. Doshi

2000-01-01

Conferences covered in this semiannual review include the TAPPI Recycling Symposium and the 9th PTS/CTP Deinking Symposium. The intent of this feature is to present a synopsis of the significant research results and industry ideas related to paper recycling reported at these conferences. Due to space constraints, we are not able to cover all of the presented papers in...

NREL Collaborates with Trucking Industry to Prioritize R&D Opportunities |

Science.gov Websites

Department drive decision-making and improve efficiency, informing long-term, high-risk research such as the Rosa Using Data to Drive Decision Making NREL's fleet test and evaluation team conducts real-world 21CTP an example of NREL's data evaluation and decision support capabilities. Using data collected in

Effects on Vocal Fold Collision and Phonation Threshold Pressure of Resonance Tube Phonation with Tube End in Water

ERIC Educational Resources Information Center

Enflo, Laura; Sundberg, Johan; Romedahl, Camilla; McAllister, Anita

2013-01-01

Purpose: Resonance tube phonation in water (RTPW) or in air is a voice therapy method successfully used for treatment of several voice pathologies. Its effect on the voice has not been thoroughly studied. This investigation analyzes the effects of RTPW on collision and phonation threshold pressures (CTP and PTP), the lowest subglottal pressure…

Effect of yeast strain and some nutritional factors on tannin composition and potential astringency of model wines.

PubMed

Rinaldi, Alessandra; Blaiotta, Giuseppe; Aponte, Maria; Moio, Luigi

2016-02-01

Nine Saccharomyces cerevisiae cultures, isolated from different sources, were tested for their ability to reduce tannins reactive towards salivary proteins, and potentially responsible for wine astringency. Strains were preliminary genetically characterized and evaluated for physiological features of technological interest. Laboratory-scale fermentations were performed in three synthetic media: CT) containing enological grape tannin; CTP) CT supplemented with organic nitrogen sources; CTPV) CTP supplemented with vitamins. Adsorption of total tannins, tannins reactive towards salivary proteins, yellow pigments, phenolics having antioxidant activity, and total phenols, characterizing the enological tannin, was determined by spectrophotometric methods after fermentation. The presence of vitamins and peptones in musts greatly influenced the adsorption of tannins reactive towards salivary proteins (4.24 g/L gallic acid equivalent), thus promoting the reduction of the potential astringency of model wines. With reference to the different phenolic classes, yeast strains showed different adsorption abilities. From a technological point of view, the yeast choice proved to be crucial in determining changes in gustative and mouthfeel profile of red wines and may assist winemakers to modulate colour and astringency of wine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Head-group specificity for feedback regulation of CTP:phosphocholine cytidylyltransferase.

PubMed Central

Jamil, H; Vance, D E

1990-01-01

The specificity of the phospholipid head-group for feedback regulation of CTP: phosphocholine cytidylyltransferase was examined in rat hepatocytes. In choline-deficient cells there is a 2-fold increase in binding of cytidylyltransferase to cellular membranes, compared with choline-supplemented cells. Supplementation of choline-deficient cells with choline, dimethylethanolamine, monomethylethanolamine or ethanolamine resulted in an increase in the concentration of the corresponding phospholipid. Release of cytidylyltransferase into cytosol was only observed in hepatocytes supplemented with choline or dimethylethanolamine. The apparent EC50 values (concn. giving half of maximal effect) for cytidylyltransferase translocation were similar for choline and dimethylethanolamine (25 and 27 microM respectively). The maximum amount of cytidylyltransferase released into cytosol with choline supplementation (1.13 m-units/mg membrane protein) was twice that (0.62) observed with dimethylethanolamine. Supplementation of choline-deficient hepatocytes with NN'-diethylethanolamine, N-ethylethanolamine or 3-aminopropanol also did not cause release of cytidylyltransferase from cellular membranes. The translocation of cytidylyltransferase appeared to be mediated by the concentration of phosphatidylcholine in the membranes and not the ratio of phosphatidylcholine to phosphatidylethanolamine. The results provide further evidence for feedback regulation of phosphatidylcholine biosynthesis by phosphatidylcholine. PMID:2173550

Oxidative damage in DNA bases revealed by UV resonant Raman spectroscopy.

PubMed

D'Amico, Francesco; Cammisuli, Francesca; Addobbati, Riccardo; Rizzardi, Clara; Gessini, Alessandro; Masciovecchio, Claudio; Rossi, Barbara; Pascolo, Lorella

2015-03-07

We report on the use of the UV Raman technique to monitor the oxidative damage of deoxynucleotide triphosphates (dATP, dGTP, dCTP and dTTP) and DNA (plasmid vector) solutions. Nucleotide and DNA aqueous solutions were exposed to hydrogen peroxide (H2O2) and iron containing carbon nanotubes (CNTs) to produce Fenton's reaction and induce oxidative damage. UV Raman spectroscopy is shown to be maximally efficient to reveal changes in the nitrogenous bases during the oxidative mechanisms occurring on these molecules. The analysis of Raman spectra, supported by numerical computations, revealed that the Fenton's reaction causes an oxidation of the nitrogenous bases in dATP, dGTP and dCTP solutions leading to the production of 2-hydroxyadenine, 8-hydroxyguanine and 5-hydroxycytosine. No thymine change was revealed in the dTTP solution under the same conditions. Compared to single nucleotide solutions, plasmid DNA oxidation has resulted in more radical damage that causes the breaking of the adenine and guanine aromatic rings. Our study demonstrates the advantage of using UV Raman spectroscopy for rapidly monitoring the oxidation changes in DNA aqueous solutions that can be assigned to specific nitrogenous bases.

Metabolic Recruitment and Directed Evolution of Nucleoside Triphosphate Uptake in Escherichia coli.

PubMed

Pezo, Valérie; Hassan, Camille; Louis, Dominique; Sargueil, Bruno; Herdewijn, Piet; Marlière, Philippe

2018-05-18

We report the design and elaboration of a selection protocol for importing a canonical substrate of DNA polymerase, thymidine triphosphate (dTTP) in Escherichia coli. Bacterial strains whose growth depend on dTTP uptake, through the action of an algal plastid transporter expressed from a synthetic gene inserted in the chromosome, were constructed and shown to withstand the simultaneous loss of thymidylate synthase and thymidine kinase. Such thyA tdk dual deletant strains provide an experimental model of tight nutritional containment for preventing dissemination of microbial GMOs. Our strains transported the four canonical dNTPs, in the following order of preference: dCTP > dATP ≥ dGTP > dTTP. Prolonged cultivation under limitation of exogenous dTTP led to the enhancement of dNTP transport by adaptive evolution. We investigated the uptake of dCTP analogues with altered sugar or nucleobase moieties, which were found to cause a loss of cell viability and an increase of mutant frequency, respectively. E. coli strains equipped with nucleoside triphosphate transporters should be instrumental for evolving organisms whose DNA genome is morphed chemically by fully substituting its canonical nucleotide components.

Biomarkers of Tobacco Exposure: Summary of an FDA-sponsored Public Workshop

PubMed Central

Chang, Cindy M.; Edwards, Selvin H.; Arab, Aarthi; Del Valle-Pinero, Arseima Y.; Yang, Ling; Hatsukami, Dorothy K.

2016-01-01

Since 2009, the United States (U.S.) Food and Drug Administration (FDA) Center for Tobacco Products (CTP) has had the authority to regulate the manufacturing, distribution, and marketing of tobacco products in order to reduce the death and disease caused by tobacco use. Biomarkers of exposure pertain to actual human exposure to chemicals arising from tobacco use and could play an important role across a number of FDA regulatory activities, including assessing new and modified risk tobacco products and identifying and evaluating potential product standards. On August 3–4, 2015, FDA/CTP hosted a public workshop focused on biomarkers of exposure with participants from government, industry, academia, and other organizations. The workshop was divided into four sessions focused on: 1) approaches to evaluating and selecting biomarkers; 2) biomarkers of exposure and relationship to disease risk; 3) currently-used biomarkers of exposure and biomarkers in development; and 4) biomarkers of exposure and the assessment of smokeless tobacco and electronic nicotine delivery systems (ENDS). This paper synthesizes the main findings from the workshop and highlights research areas that could further strengthen the science around biomarkers of exposure and help determine their application in tobacco product regulation. PMID:28151705

Organo luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes

DOEpatents

Weiss, Shimon; Bruchez, Jr., Marcel; Alivisatos, Paul

2006-09-05

A semiconductor nanocrystal compound is described capable of linking to an affinity molecule. The compound comprises (1) a semiconductor nanocrystal capable of emitting electromagnetic radiation and/or absorbing energy, and/or scattering or diffracting electromagnetic radiation--when excited by an electromagnetic radiation source or a particle beam; and (2) at least one linking agent, having a first portion linked to the semiconductor nanocrystal and a second portion capable of linking to an affinity molecule. The compound is linked to an affinity molecule to form a semiconductor nanocrystal probe capable of bonding with a detectable substance. subsequent exposure to excitation energy will excite the semiconductor nanocrystal in the probe causing the emission of electromagnetic radiation. Further described are processes for respectively: making the luminescent semiconductor nanocrystal compound; making the semiconductor nanocrystal probe; and using the probe to determine the presence of a detectable substance in a material.

Organo luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes

DOEpatents

Weiss, Shimon [Pinole, CA; Bruchez, Jr., Marcel; Alivisatos, Paul [Oakland, CA

2004-03-02

A semiconductor nanocrystal compound is described capable of linking to an affinity molecule. The compound comprises (1) a semiconductor nanocrystal capable of emitting electromagnetic radiation and/or absorbing energy, and/or scattering or diffracting electromagnetic radiation--when excited by an electromagnetic radiation source or a particle beam; and (2) at least one linking agent, having a first portion linked to the semiconductor nanocrystal and a second portion capable of linking to an affinity molecule. The compound is linked to an affinity molecule to form a semiconductor nanocrystal probe capable of bonding with a detectable substance. Subsequent exposure to excitation energy will excite the semiconductor nanocrystal in the probe, causing the emission of electromagnetic radiation. Further described are processes for respectively: making the semiconductor nanocrystal compound; making the semiconductor nanocrystal probe; and using the probe to determine the presence of a detectable substance in a material.

Organo luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes

DOEpatents

Weiss, Shimon; Bruchez, Jr., Marcel; Alivisatos, Paul

2005-08-09

A semiconductor nanocrystal compound is described capable of linking to an affinity molecule. The compound comprises (1) a semiconductor nanocrystal capable of emitting electromagnetic radiation and/or absorbing energy, and/or scattering or diffracting electromagnetic radiation--when excited by an electromagnetic radiation source or a particle beam; and (2) at least one linking agent, having a first portion linked to the semiconductor nanocrystal and a second portion capable of linking to an affinity molecule. The compound is linked to an affinity molecule to form a semiconductor nanocrystal probe capable of bonding with a detectable substance. Subsequent exposure to excitation energy will excite the semiconductor nanocrystal in the probe causing the emission of electromagnetic radiation. Further described are processes for respectively: making the luminescent semiconductor nanocrystal compound; making the semiconductor nanocrystal probe; and using the probe to determine the presence of a detectable substance in a material.

Apparatus for processing electromagnetic radiation and method

NASA Technical Reports Server (NTRS)

Gatewood, George D. (Inventor)

1983-01-01

Measuring apparatus including a ruled member having alternate transparent and opaque zones. An optical coupler connecting the ruled member with electromagnetic radiation-conversion apparatus. The conversion apparatus may include a photomultiplier and a discriminator. Radiation impinging on the ruled member will, in part, be converted to electrical pulses which correspond to the intensity of the radiation. A method of processing electromagnetic radiation includes providing a member having alternating dark and light zones, establishing movement of the member through the beam of electromagnetic radiation with the dark zones interrupting passage of radiation through the rule, providing an optical coupler to connect a portion of the radiation with a conversion station where the radiation portion is converted into an electrical pulse which is related to the intensity of the radiation received at the conversion station. The electrical pulses may be counted and the digitized signals stored or permanently recorded to produce positional information.

Organo luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes

DOEpatents

Weiss, Shimon; Bruchez, Jr., Marcel; Alivisatos, Paul

2002-01-01

A semiconductor nanocrystal compound is described capable of linking to an affinity molecule. The compound comprises (1) a semiconductor nanocrystal capable of emitting electromagnetic radiation and/or absorbing energy, and/or scattering or diffracting electromagnetic radiation--when excited by an electromagnetic radiation source or a particle beam; and (2) at least one linking agent, having a first portion linked to the semiconductor nanocrystal and a second portion capable of linking to an affity molecule. The compound is linked to an affinity molecule to form a semiconductor nanocrystal probe capable of bonding with a detectable substance. Subsequent exposure to excitation energy will excite the semiconductor nanocrystal in he probe, causing the emission of electromagnetic radiation. Further described are processes for respectively: making the semiconductor nanocrystal compound; making the semiconductor nanocrystal probe; and using the probe to determine the presence of a detectable substance in a material.

Electromagnetic processes in the atmosphere of pulsars

NASA Technical Reports Server (NTRS)

Yukhimuk, A. K.

1974-01-01

The work consists of two parts. The first deals with the fine structure of radio pulses. Based on kinetic theory, processes occurring in the plasma shell of a pulsar when external electromagnetic radiation is present are investigated. It is shown that electromagnetic waves cause electrons to drift relative to ions, and initiate longitudinal oscillations. A dispersion equation describing the longitudinal oscillations in magnetized plasma is derived. Conditions for excitation of oscillations are found. Correlation functions of electron density are calculated, along with the coefficients of electromagnetic wave scattering. It is shown that variations in the amplitude of pulsar pulses are associated with scintillations caused by fluctuations in the plasma electron density. The second part of the study presents a mechanism for the radio emission of pulsars. The model of a rotating and a pulsating star, a neutron star with dipolar or more complex magnetic field, is examined.

Impact of electromagnetic fields on stem cells: common mechanisms at the crossroad between adult neurogenesis and osteogenesis

PubMed Central

Leone, Lucia; Podda, Maria Vittoria; Grassi, Claudio

2015-01-01

In the recent years adult neural and mesenchymal stem cells have been intensively investigated as effective resources for repair therapies. In vivo and in vitro studies have provided insights on the molecular mechanisms underlying the neurogenic and osteogenic processes in adulthood. This knowledge appears fundamental for the development of targeted strategies to manipulate stem cells. Here we review recent literature dealing with the effects of electromagnetic fields on stem cell biology that lends support to their use as a promising tool to positively influence the different steps of neurogenic and osteogenic processes. We will focus on recent studies revealing that extremely-low frequency electromagnetic fields enhance adult hippocampal neurogenesis by inducing epigenetic modifications on the regulatory sequences of genes responsible for neural stem cell proliferation and neuronal differentiation. In light of the emerging critical role played by chromatin modifications in maintaining the stemness as well as in regulating stem cell differentiation, we will also attempt to exploit epigenetic changes that can represent common targets for electromagnetic field effects on neurogenic and osteogenic processes. PMID:26124705

Sensing network for electromagnetic fields generated by seismic activities

NASA Astrophysics Data System (ADS)

Gershenzon, Naum I.; Bambakidis, Gust; Ternovskiy, Igor V.

2014-06-01

The sensors network is becoming prolific and play now increasingly more important role in acquiring and processing information. Cyber-Physical Systems are focusing on investigation of integrated systems that includes sensing, networking, and computations. The physics of the seismic measurement and electromagnetic field measurement requires special consideration how to design electromagnetic field measurement networks for both research and detection earthquakes and explosions along with the seismic measurement networks. In addition, the electromagnetic sensor network itself could be designed and deployed, as a research tool with great deal of flexibility, the placement of the measuring nodes must be design based on systematic analysis of the seismic-electromagnetic interaction. In this article, we review the observations of the co-seismic electromagnetic field generated by earthquakes and man-made sources such as vibrations and explosions. The theoretical investigation allows the distribution of sensor nodes to be optimized and could be used to support existing geological networks. The placement of sensor nodes have to be determined based on physics of electromagnetic field distribution above the ground level. The results of theoretical investigations of seismo-electromagnetic phenomena are considered in Section I. First, we compare the relative contribution of various types of mechano-electromagnetic mechanisms and then analyze in detail the calculation of electromagnetic fields generated by piezomagnetic and electrokinetic effects.

Electromagnetic Levitation: A Useful Tool in Microgravity Research

NASA Technical Reports Server (NTRS)

Szekely, Julian; Schwartz, Elliot; Hyers, Robert

1995-01-01

Electromagnetic levitation is one area of the electromagnetic processing of materials that has uses for both fundamental research and practical applications. This technique was successfully used on the Space Shuttle Columbia during the Spacelab IML-2 mission in July 1994 as a platform for accurately measuring the surface tensions of liquid metals and alloys. In this article, we discuss the key transport phenomena associated with electromagnetic levitation, the fundamental relationships associated with thermophysical property measurement that can be made using this technique, reasons for working in microgravity, and some of the results obtained from the microgravity experiments.

A study of the electromagnetic shielding mechanisms in the GHz frequency range of graphene based composite layers

NASA Astrophysics Data System (ADS)

Drakakis, E.; Kymakis, E.; Tzagkarakis, G.; Louloudakis, D.; Katharakis, M.; Kenanakis, G.; Suchea, M.; Tudose, V.; Koudoumas, E.

2017-03-01

We report on the mechanisms of the electromagnetic interference shielding effect of graphene based paint like composite layers. In particular, we studied the absorption and reflection of electromagnetic radiation in the 4-20 GHz frequency of various dispersions employing different amounts of graphene nanoplatelets, polyaniline, and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate), special attention given on the relative contribution of each process in the shielding effect. Moreover, the influence of the composition, the thickness and the conductivity of the composite layers on the electromagnetic shielding was also examined.

Development and program implementation of elements for identification of the electromagnet condition for movable element position control

NASA Astrophysics Data System (ADS)

Leukhin, R. I.; Shaykhutdinov, D. V.; Shirokov, K. M.; Narakidze, N. D.; Vlasov, A. S.

2017-02-01

Developing the experimental design of new electromagnetic constructions types in engineering industry enterprises requires solutions of two major problems: regulator’s parameters setup and comprehensive testing of electromagnets. A weber-ampere characteristic as a data source for electromagnet condition identification was selected. Present article focuses on development and implementation of the software for electromagnetic drive control system based on the weber-ampere characteristic measuring. The software for weber-ampere characteristic data processing based on artificial neural network is developed. Results of the design have been integrated into the program code in LabVIEW environment. The license package of LabVIEW graphic programming was used. The hardware is chosen and possibility of its use for control system implementation was proved. The trained artificial neural network defines electromagnetic drive effector position with minimal error. Developed system allows to control the electromagnetic drive powered by the voltage source, the current source and hybrid sources.

Analysis of electromagnetic interference from power system processing and transmission components for Space Station Freedom

NASA Technical Reports Server (NTRS)

Barber, Peter W.; Demerdash, Nabeel A. O.; Wang, R.; Hurysz, B.; Luo, Z.

1991-01-01

The goal is to analyze the potential effects of electromagnetic interference (EMI) originating from power system processing and transmission components for Space Station Freedom.The approach consists of four steps: (1) develop analytical tools (models and computer programs); (2) conduct parameterization studies; (3) predict the global space station EMI environment; and (4) provide a basis for modification of EMI standards.

Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis.

PubMed

Radha Krishna, Yellapu; Saraswat, Vivek Anand; Das, Khaunish; Himanshu, Goel; Yachha, Surender Kumar; Aggarwal, Rakesh; Choudhuri, Gour

2009-03-01

Acute hepatitis A and E are recognized triggers of hepatic decompensation in patients with cirrhosis, particularly from the Indian subcontinent. However, the resulting acute-on-chronic liver failure (ACLF) has not been well characterized and no large studies are available. Our study aimed to evaluate the clinical profile and predictors of 3-month mortality in patients with this distinctive form of liver failure. ACLF was diagnosed in patients with acute hepatitis A or E [abrupt rise in serum bilirubin and/or alanine aminotransferase with positive immunoglobulin M anti-hepatitis A virus (HAV)/anti-hepatitis E virus (HEV)] presenting with clinical evidence of liver failure (significant ascites and/or hepatic encephalopathy) and clinical, biochemical, endoscopic (oesophageal varices at least grade II in size), ultrasonographical (presence of nodular irregular liver with porto-systemic collaterals) or histological evidence of cirrhosis. Clinical and laboratory profile were evaluated, predictors of 3-month mortality were determined using univariate and multivariate logistic regression and a prognostic model was constructed. Receiver-operating curves were plotted to measure performance of the present prognostic model, model for end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) score. ACLF occurred in 121 (3.75%) of 3220 patients (mean age 36.3+/-18.0 years; M:F 85:36) with liver cirrhosis admitted from January 2000 to June 2006. It was due to HEV in 80 (61.1%), HAV in 33 (27.2%) and both in 8 (6.1%). The underlying liver cirrhosis was due to HBV (37), alcohol (17), Wilson's disease (8), HCV (5), autoimmune (6), Budd-Chiari syndrome (2), haemochromatosis (2) and was cryptogenic in the rest (42). Common presentations were jaundice (100%), ascites (78%) and hepatic encephalopathy (55%). Mean (SD) CTP score was 11.4+/-1.6 and mean MELD score was 28.6+/-9.06. Three-month mortality was 54 (44.6%). Complications seen were sepsis in 42 (31.8%), renal failure in 45 (34%), spontaneous bacterial peritonitis in 27 (20.5%), UGI bleeding in 15(11%) and hyponatraemia in 50 (41.3%). On univariate analysis, ascites, hepatic encephalopathy, renal failure, GI bleeding, total bilirubin, hyponatraemia and coagulopathy were significant predictors of mortality. Multivariate analysis revealed grades 3 and 4 HE [odds ratio (OR 32.1)], hyponatraemia (OR 9.2) and renal failure (OR 16.8) as significant predictors of 3-month mortality and a prognostic model using these predictors was constructed. Areas under the curve for the present predicted prognostic model, MELD, and CTP were 0.952, 0.941 and 0.636 respectively. ACLF due to hepatitis A or E super infection results in significant short-term mortality. The predictors of ominous outcome include grades 3 and 4 encephalopathy, hyponatraemia and renal failure. Present prognostic model and MELD scoring system were better predictors of 3-month outcome than CTP score in these patients. Early recognition of those with dismal prognosis may permit timely use of liver replacement/supportive therapies.

Electric converters of electromagnetic strike machine with battery power

NASA Astrophysics Data System (ADS)

Usanov, K. M.; Volgin, A. V.; Kargin, V. A.; Moiseev, A. P.; Chetverikov, E. A.

2018-03-01

At present, the application of pulse linear electromagnetic engines to drive strike machines for immersion of rod elements into the soil, strike drilling of shallow wells, dynamic probing of soils is recognized as quite effective. The pulse linear electromagnetic engine performs discrete consumption and conversion of electrical energy into mechanical work. Pulse dosing of a stream transmitted by the battery source to the pulse linear electromagnetic engine of the energy is provided by the electrical converter. The electric converters with the control of an electromagnetic strike machine as functions of time and armature movement, which form the unipolar supply pulses of voltage and current necessary for the normal operation of a pulse linear electromagnetic engine, are proposed. Electric converters are stable in operation, implement the necessary range of output parameters control determined by the technological process conditions, have noise immunity and automatic disconnection of power supply in emergency modes.

[Organization of monitoring of electromagnetic radiation in the urban environment].

PubMed

Savel'ev, S I; Dvoeglazova, S V; Koz'min, V A; Kochkin, D E; Begishev, M R

2008-01-01

The authors describe new current approaches to monitoring the environment, including the sources of electromagnetic radiation and noise. Electronic maps of the area under study are shown to be made, by constructing the isolines or distributing the actual levels of controlled factors. These current approaches to electromagnetic and acoustic monitoring make it possible to automate a process of measurements, to analyze the established situation, and to simplify the risk controlling methodology.

Organo Luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes

DOEpatents

Weiss, Shimon; Bruchez, Jr., Marcel; Alivisatos, Paul

1999-01-01

A luminescent semiconductor nanocrystal compound is described which is capable of linking to an affinity molecule. The compound comprises (1) a semiconductor nanocrystal capable of emitting electromagnetic radiation (luminescing) in a narrow wavelength band and/or absorbing energy, and/or scattering or diffracting electromagnetic radiation--when excited by an electromagnetic radiation source (of narrow or broad bandwidth) or a particle beam; and (2) at least one linking agent, having a first portion linked to the semiconductor nanocrystal and a second portion capable of linking to an affinity molecule. The luminescent semiconductor nanocrystal compound is linked to an affinity molecule to form an organo luminescent semiconductor nanocrystal probe capable of bonding with a detectable substance in a material being analyzed, and capable of emitting electromagnetic radiation in a narrow wavelength band and/or absorbing, scattering, or diffracting energy when excited by an electromagnetic radiation source (of narrow or broad bandwidth) or a particle beam. The probe is stable to repeated exposure to light in the presence of oxygen and/or other radicals. Further described is a process for making the luminescent semiconductor nanocrystal compound and for making the organo luminescent semiconductor nanocrystal probe comprising the luminescent semiconductor nanocrystal compound linked to an affinity molecule capable of bonding to a detectable substance. A process is also described for using the probe to determine the presence of a detectable substance in a material.

High-resolution Mapping of Permafrost and Soil Freeze/thaw Dynamics in the Tibetan Plateau Based on Multi-sensor Satellite Observations

NASA Astrophysics Data System (ADS)

Zhang, W.; Yi, Y.; Yang, K.; Kimball, J. S.

2016-12-01

The Tibetan Plateau (TP) is underlain by the world's largest extent of alpine permafrost ( 2.5×106 km2), dominated by sporadic and discontinuous permafrost with strong sensitivity to climate warming. Detailed permafrost distributions and patterns in most of the TP region are still unknown due to extremely sparse in-situ observations in this region characterized by heterogeneous land cover and large temporal dynamics in surface soil moisture conditions. Therefore, satellite-based temperature and moisture observations are essential for high-resolution mapping of permafrost distribution and soil active layer changes in the TP region. In this study, we quantify the TP regional permafrost distribution at 1-km resolution using a detailed satellite data-driven soil thermal process model (GIPL2). The soil thermal model is calibrated and validated using in-situ soil temperature/moisture observations from the CAMP/Tibet field campaign (9 sites: 0-300 cm soil depth sampling from 1997-2007), a multi-scale soil moisture and temperature monitoring network in the central TP (CTP-SMTMN, 57 sites: 5-40 cm, 2010-2014) and across the whole plateau (China Meteorology Administration, 98 sites: 0-320 cm, 2000-2015). Our preliminary results using the CAMP/Tibet and CTP-SMTMN network observations indicate strong controls of surface thermal and soil moisture conditions on soil freeze/thaw dynamics, which vary greatly with underlying topography, soil texture and vegetation cover. For regional mapping of soil freeze/thaw and permafrost dynamics, we use the most recent soil moisture retrievals from the NASA SMAP (Soil Moisture Active Passive) sensor to account for the effects of temporal soil moisture dynamics on soil thermal heat transfer, with surface thermal conditions defined by MODIS (Moderate Resolution Imaging Spectroradiometer) land surface temperature records. Our study provides the first 1-km map of spatial patterns and recent changes of permafrost conditions in the TP.

Assessment of in vitro COPD models for tobacco regulatory science: Workshop proceedings, conclusions and paths forward for in vitro model use.

PubMed

Behrsing, Holger; Raabe, Hans; Manuppello, Joseph; Bombick, Betsy; Curren, Rodger; Sullivan, Kristie; Sethi, Sanjay; Phipps, Richard; Tesfaigzi, Yohannes; Yan, Sherwin; D'Ruiz, Carl; Tarran, Robert; Constant, Samuel; Phillips, Gary; Gaça, Marianna; Hayden, Patrick; Cao, Xuefei; Mathis, Carole; Hoeng, Julia; Braun, Armin; Hill, Erin

2016-05-01

The Family Smoking Prevention and Tobacco Control Act of 2009 established the Food and Drug Administration Center for Tobacco Products (FDA-CTP), and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed 'modified risk'. On 8-10 December 2014, IIVS organised a workshop conference, entitled Assessment of In Vitro COPD Models for Tobacco Regulatory Science, to bring together stakeholders representing regulatory agencies, academia, industry and animal protection, to address the research priorities articulated by the FDA-CTP. Specific topics were covered to assess the status of current in vitro technologies as they are applied to understanding the adverse pulmonary events resulting from tobacco product exposure, and in particular, the progression of chronic obstructive pulmonary disease (COPD). The four topics covered were: a) Inflammation and Oxidative Stress; b) Ciliary Dysfunction and Ion Transport; c) Goblet Cell Hyperplasia and Mucus Production; and d) Parenchymal/Bronchial Tissue Destruction and Remodelling. The 2.5 day workshop included 18 expert speakers, plus poster sessions, networking and breakout sessions, which identified key findings and provided recommendations to advance the in vitro technologies and assays used to evaluate tobacco-induced disease etiologies. The workshop summary was reported at the 2015 Society of Toxicology Annual Meeting, and the recommendations led to an IIVS-organised technical workshop in June 2015, entitled Goblet Cell Hyperplasia, Mucus Production, and Ciliary Beating Assays, to assess these assays and to conduct a proof-of-principle multi-laboratory exercise to determine their suitability for standardisation. Here, we report on the proceedings, recommendations and outcomes of the December 2014 workshop, including paths forward to continue the development of non-animal methods to evaluate tissue responses that model the disease processes that may lead to COPD, a major cause of mortality worldwide. 2016 FRAME.

[Changes in the chromatin structure of lymphoid cells under the influence of low-intensity extremely high-frequency electromagnetic radiation against the background of inflammatory process].

PubMed

Gapeev, A B; Romanova, N A; Chemeris, N K

2011-01-01

Using the alkaline single cell gel electrophoresis technique (comet assay), changes in chromatin structure of peripheral blood leukocytes and peritoneal neutrophils have been studied in mice exposed to low-intensity extremely high-frequency electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, 20 min at 1 h after induction of inflammation) against the background of the systemic inflammatory process. It was revealed that the exposure of mice with the developing inflammation leads to a pronounced decrease in the level of DNA damage to peripheral blood leukocytes and peritoneal neutrophils. It is supposed that the changes in the chromatin structure of lymphoid cells have a genoprotective character in the inflammatory process and can underlie the mechanisms of realization of antiinflammatory effects of the electromagnetic radiation.

Electromagnetic Processing as a Way of Increasing Microbiological Safety of Animal Waste

NASA Astrophysics Data System (ADS)

Soboleva, O. M.; Kolosova, M. M.; Filipovich, L. A.; Aksenov, V. A.

2017-05-01

The article shows the possibility of using the electromagnetic field of ultrahigh frequency (EMF UHF) for drying and disinfecting of such animal waste as pig manure and poultry droppings. The studied modes included the following options: processing exposure of 60, 90, 120 sec, the capacity of 60 kW, the frequency of 915 MHz. The method of UHF processing of manure and poultry droppings is environmentally safe and effective in neutralizing the pathogenic microflora, as well as larvae and eggs of worms. The following processing mode of animal waste in the electromagnetic field of ultrahigh frequency was recognized as optimal: exposure of 90 seconds, the capacity of 60 kW, the frequency of 915 MHz. This option leads to the complete destruction of pathogenic and conditionally pathogenic microorganisms, as well as the eggs and larvae of worms. As a result of this processing, a high level of microbiological safety of pig manure and poultry droppings is achieved that allows using them as organic fertilizers. The peculiarities of some species of pathogenic fungi developing on the surface of the wheat grain are shown. Pre-processed animal waste (pig manure and and poultry droppings) were applied in experimental variants. Used organic fertilizers underwent electromagnetic processing of ultra-high frequency. The qualitative composition of the microflora on the surface of the grain depends on the type of animal waste (manure or droppings) and used dose. The safest part of the microflora of grain was marked with the application of the UHF-processed pig manure and poultry droppings in doses of 10 t/ha.

Practical UXO Classification: Enhanced Data Processing Strategies for Technology Transition - Fort Ord: Dynamic and Cued Metalmapper Processing and Classification

DTIC Science & Technology

2017-06-06

OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for...Geophysical Mapping, Electromagnetic Induction, Instrument Verification Strip, Time Domain Electromagnetic, Unexploded Ordnance 16. SECURITY...Munitions Response QA Quality Assurance QC Quality Control ROC Receiver Operating Characteristic RTK Real- time Kinematic s Second SNR

Pressure Autoregulation Measurement Techniques in Adult Traumatic Brain Injury, Part I: A Scoping Review of Intermittent/Semi-Intermittent Methods.

PubMed

Zeiler, Frederick A; Donnelly, Joseph; Calviello, Leanne; Menon, David K; Smielewski, Peter; Czosnyka, Marek

2017-12-01

The purpose of this study was to perform a systematic, scoping review of commonly described intermittent/semi-intermittent autoregulation measurement techniques in adult traumatic brain injury (TBI). Nine separate systematic reviews were conducted for each intermittent technique: computed tomographic perfusion (CTP)/Xenon-CT (Xe-CT), positron emission tomography (PET), magnetic resonance imaging (MRI), arteriovenous difference in oxygen (AVDO 2 ) technique, thigh cuff deflation technique (TCDT), transient hyperemic response test (THRT), orthostatic hypotension test (OHT), mean flow index (Mx), and transfer function autoregulation index (TF-ARI). MEDLINE ® , BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to December 2016), and reference lists of relevant articles were searched. A two tier filter of references was conducted. The total number of articles utilizing each of the nine searched techniques for intermittent/semi-intermittent autoregulation techniques in adult TBI were: CTP/Xe-CT (10), PET (6), MRI (0), AVDO 2 (10), ARI-based TCDT (9), THRT (6), OHT (3), Mx (17), and TF-ARI (6). The premise behind all of the intermittent techniques is manipulation of systemic blood pressure/blood volume via either chemical (such as vasopressors) or mechanical (such as thigh cuffs or carotid compression) means. Exceptionally, Mx and TF-ARI are based on spontaneous fluctuations of cerebral perfusion pressure (CPP) or mean arterial pressure (MAP). The method for assessing the cerebral circulation during these manipulations varies, with both imaging-based techniques and TCD utilized. Despite the limited literature for intermittent/semi-intermittent techniques in adult TBI (minus Mx), it is important to acknowledge the availability of such tests. They have provided fundamental insight into human autoregulatory capacity, leading to the development of continuous and more commonly applied techniques in the intensive care unit (ICU). Numerous methods of intermittent/semi-intermittent pressure autoregulation assessment in adult TBI exist, including: CTP/Xe-CT, PET, AVDO 2 technique, TCDT-based ARI, THRT, OHT, Mx, and TF-ARI. MRI-based techniques in adult TBI are yet to be described, with the main focus of MRI techniques on metabolic-based cerebrovascular reactivity (CVR) and not pressure-based autoregulation.

Proposal for a New Predictive Model of Short-Term Mortality After Living Donor Liver Transplantation due to Acute Liver Failure.

PubMed

Chung, Hyun Sik; Lee, Yu Jung; Jo, Yun Sung

2017-02-21

BACKGROUND Acute liver failure (ALF) is known to be a rapidly progressive and fatal disease. Various models which could help to estimate the post-transplant outcome for ALF have been developed; however, none of them have been proved to be the definitive predictive model of accuracy. We suggest a new predictive model, and investigated which model has the highest predictive accuracy for the short-term outcome in patients who underwent living donor liver transplantation (LDLT) due to ALF. MATERIAL AND METHODS Data from a total 88 patients were collected retrospectively. King's College Hospital criteria (KCH), Child-Turcotte-Pugh (CTP) classification, and model for end-stage liver disease (MELD) score were calculated. Univariate analysis was performed, and then multivariate statistical adjustment for preoperative variables of ALF prognosis was performed. A new predictive model was developed, called the MELD conjugated serum phosphorus model (MELD-p). The individual diagnostic accuracy and cut-off value of models in predicting 3-month post-transplant mortality were evaluated using the area under the receiver operating characteristic curve (AUC). The difference in AUC between MELD-p and the other models was analyzed. The diagnostic improvement in MELD-p was assessed using the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS The MELD-p and MELD scores had high predictive accuracy (AUC >0.9). KCH and serum phosphorus had an acceptable predictive ability (AUC >0.7). The CTP classification failed to show discriminative accuracy in predicting 3-month post-transplant mortality. The difference in AUC between MELD-p and the other models had statistically significant associations with CTP and KCH. The cut-off value of MELD-p was 3.98 for predicting 3-month post-transplant mortality. The NRI was 9.9% and the IDI was 2.9%. CONCLUSIONS MELD-p score can predict 3-month post-transplant mortality better than other scoring systems after LDLT due to ALF. The recommended cut-off value of MELD-p is 3.98.

3'-Azido-2',3'-dideoxythymidine induced deficiency of thymidine kinases 1, 2 and deoxycytidine kinase in H9 T-lymphoid cells.

PubMed

Gröschel, Bettina; Kaufmann, Andreas; Höver, Gerold; Cinatl, Jaroslav; Doerr, Hans Wilhelm; Noordhuis, Paul; Loves, Willem J P; Peters, Godefridus J; Cinatl, Jindrich

2002-07-15

Continuous cultivation of T-lymphoid H9 cells in the presence of 3'-azido-2',3'-dideoxythymidine (AZT) resulted in a cell variant cross-resistant to both thymidine and deoxycytidine analogs. Cytotoxic effects of AZT, 2',3'-didehydro-3'-deoxythymidine as well as different deoxycytidine analogs such as 2',3'-dideoxycytidine, 2',2'-difluoro-2'-deoxycytidine (dFdC) and 1-ss-D-arabinofuranosylcytosine (Ara-C) were strongly reduced in H9 cells continuously exposed to AZT when compared to parental cells (>8.3-, >6.6-, >9.1-, 5 x 10(4)-, 5 x 10(3)-fold, respectively). Moreover, anti-HIV-1 effects of AZT, d4T, ddC and 2',3'-dideoxy-3'-thiacytidine (3TC) were significantly diminished (>222-, >25-, >400-, >200-fold, respectively) in AZT-resistant H9 cells. Study of cellular mechanisms responsible for cross-resistance to pyrimidine analogs in AZT-resistant H9 cells revealed decreased mRNA levels of thymidine kinase 1 (TK1) and lack of deoxycytidine kinase (dCK) mRNA expression. The loss of dCK gene expression was confirmed by western blot analysis of dCK protein as well as dCK enzyme activity assay. Moreover, enzyme activity of TK1 and TK2 was reduced in AZT-resistant cells. In order to determine whether lack of dCK affected the formation of the active triphosphate of the deoxycytidine analog dFdC, dFdCTP accumulation and retention was measured in H9 parental and AZT-resistant cells after exposure to 1 and 10 microM dFdC. Parental H9 cells accumulated about 30 and 100 pmol dFdCTP/10(6) cells after 4hr, whereas in AZT-resistant cells no dFdCTP accumulation was detected. These results demonstrate that continuous treatment of H9 cells in the presence of AZT selected for a thymidine analog resistant cell variant with cross-resistance to deoxycytidine analogs, due to deficiency in TK1, TK2, and dCK.

Study protocol: cross-national comparative case study of recovery-focused mental health care planning and coordination (COCAPP).

PubMed

Simpson, Alan; Hannigan, Ben; Coffey, Michael; Jones, Aled; Barlow, Sally; Cohen, Rachel; Všetečková, Jitka; Faulkner, Alison; Haddad, Mark

2015-07-03

The collaborative care planning study (COCAPP) is a cross-national comparative study of care planning and coordination in community mental healthcare settings. The context and delivery of mental health care is diverging between the countries of England and Wales whilst retaining points of common interest, hence providing a rich geographical comparison for research. Across England the key vehicle for the provision of recovery-focused, personalised, collaborative mental health care is the care programme approach (CPA). The CPA is a form of case management introduced in England in 1991, then revised in 2008. In Wales the CPA was introduced in 2003 but has now been superseded by The Mental Health (Care Co-ordination and Care and Treatment Planning) (CTP) Regulations (Mental Health Measure), a new statutory framework. In both countries, the CPA/CTP requires providers to: comprehensively assess health/social care needs and risks; develop a written care plan (which may incorporate risk assessments, crisis and contingency plans, advanced directives, relapse prevention plans, etc.) in collaboration with the service user and carer(s); allocate a care coordinator; and regularly review care. The overarching aim of this study is to identify and describe the factors that ensure CPA/CTP care planning and coordination is personalised, recovery-focused and conducted collaboratively. COCAPP will employ a concurrent transformative mixed methods approach with embedded case studies. Phase 1 (Macro-level) will consider the national context through a meta-narrative mapping (MNM) review of national policies and the relevant research literature. Phase 2 (Meso-level and Micro-level) will include in-depth micro-level case studies of everyday 'frontline' practice and experience with detailed qualitative data from interviews and reviews of individual care plans. This will be nested within larger meso-level survey datasets, senior-level interviews and policy reviews in order to provide potential explanations and understanding. COCAPP will help identify the key components that support and hinder the provision of personalised, recovery-focused care planning and provide an informed rationale for a future planned intervention and evaluation.

Use of dry citrus pulp or soybean hulls as a replacement for corn grain in energy and nitrogen partitioning, methane emissions, and milk performance in lactating Murciano-Granadina goats.

PubMed

López, M C; Estellés, F; Moya, V J; Fernández, C

2014-12-01

The aim of this study was to assess the effect of substitution of dietary corn grain by dry citrus pulp or soybean hulls on energy and nitrogen partitioning, substrate oxidation, methane emission, and milk performance in dairy goats during midlactation. Twelve multiparous Murciano-Granadina goats of similar body weight (41.7 ± 2.8 kg) were split in 3 groups in an incomplete crossover design. One group of 4 goats was fed a mixed ration with 605 g/kg of dry matter of corn grain (CRG), another group replaced corn grain with dry citrus pulp (CTP), and the last with soybean hulls (SYH). The goats were allocated to individual metabolism cages. After 14 d of adaptation, feed intake, total fecal and urine output, and milk yield were recorded daily over a 5-d period. Then, gas exchange measurements were recorded by a mobile open-circuit indirect calorimetry system using a head box. Dry matter intake was similar for all 3 groups (1.53 kg/d, on average). Total replacement of the concentrate with fibrous by-products increased fiber apparent digestibility. The metabolizable energy intake was significantly greater for diet CRG than SYH (1,193 vs. 1,079 kJ/kg of BW⁰·⁷⁵, respectively), CTP showed an intermediate value. The heat production was higher for the fiber diet than starchy diet (908 vs. 843 kJ/kg of BW⁰·⁷⁵ for SYH and CRG, respectively). The efficiency of use of metabolizable energy for milk production obtained by regression was 0.59. Goats fed CTP and SYH diets produced similar CH₄ emissions (34.8 g/d, on average), significantly higher compared with goats fed the CRG diet (24.7 g/d). Goats of the 3 treatments were in negative energy balance, so the oxidation of fat was greater than for carbohydrates. No significant differences were observed for milk production (1.72 kg/d), and milk fat was significantly greater for a more fibrous diet compared with a starchy diet (6.57 vs. 4.95% in SYH and CRG, respectively).

Anthropogenic electromagnetic noise disrupts magnetic compass orientation in a migratory bird.

PubMed

Engels, Svenja; Schneider, Nils-Lasse; Lefeldt, Nele; Hein, Christine Maira; Zapka, Manuela; Michalik, Andreas; Elbers, Dana; Kittel, Achim; Hore, P J; Mouritsen, Henrik

2014-05-15

Electromagnetic noise is emitted everywhere humans use electronic devices. For decades, it has been hotly debated whether man-made electric and magnetic fields affect biological processes, including human health. So far, no putative effect of anthropogenic electromagnetic noise at intensities below the guidelines adopted by the World Health Organization has withstood the test of independent replication under truly blinded experimental conditions. No effect has therefore been widely accepted as scientifically proven. Here we show that migratory birds are unable to use their magnetic compass in the presence of urban electromagnetic noise. When European robins, Erithacus rubecula, were exposed to the background electromagnetic noise present in unscreened wooden huts at the University of Oldenburg campus, they could not orient using their magnetic compass. Their magnetic orientation capabilities reappeared in electrically grounded, aluminium-screened huts, which attenuated electromagnetic noise in the frequency range from 50 kHz to 5 MHz by approximately two orders of magnitude. When the grounding was removed or when broadband electromagnetic noise was deliberately generated inside the screened and grounded huts, the birds again lost their magnetic orientation capabilities. The disruptive effect of radiofrequency electromagnetic fields is not confined to a narrow frequency band and birds tested far from sources of electromagnetic noise required no screening to orient with their magnetic compass. These fully double-blinded tests document a reproducible effect of anthropogenic electromagnetic noise on the behaviour of an intact vertebrate.

Fracture induced electromagnetic emissions: extending laboratory findings by observations at the geophysical scale

NASA Astrophysics Data System (ADS)

Potirakis, Stelios M.; Contoyiannis, Yiannis; Kopanas, John; Kalimeris, Anastasios; Antonopoulos, George; Peratzakis, Athanasios; Eftaxias, Konstantinos; Nomicos, Constantinos

2014-05-01

Under natural conditions, it is practically impossible to install an experimental network on the geophysical scale using the same instrumentations as in laboratory experiments for understanding, through the states of stress and strain and their time variation, the laws that govern the friction during the last stages of EQ generation, or to monitor (much less to control) the principal characteristics of a fracture process. Fracture-induced electromagnetic emissions (EME) in a wide range of frequency bands are sensitive to the micro-structural chances. Thus, their study constitutes a nondestructive method for the monitoring of the evolution of damage process at the laboratory scale. It has been suggested that fracture induced MHz-kHz electromagnetic (EM) emissions, which emerge from a few days up to a few hours before the main seismic shock occurrence permit a real time monitoring of the damage process during the last stages of earthquake preparation, as it happens at the laboratory scale. Since the EME are produced both in the case of the laboratory scale fracture and the EQ preparation process (geophysical scale fracture) they should present similar characteristics in these two scales. Therefore, both the laboratory experimenting scientists and the experimental scientists studying the pre-earthquake EME could benefit from each- other's results. Importantly, it is noted that when studying the fracture process by means of laboratory experiments, the fault growth process normally occurs violently in a fraction of a second. However, a major difference between the laboratory and natural processes is the order-of-magnitude differences in scale (in space and time), allowing the possibility of experimental observation at the geophysical scale for a range of physical processes which are not observable at the laboratory scale. Therefore, the study of fracture-induced EME is expected to reveal more information, especially for the last stages of the fracture process, when it is conducted at the geophysical scale. As a characteristic example, we discuss about the case of electromagnetic silence before the global rupture that was first observed in preseismic EME and recently was also observed in the EME measured during laboratory fracture experiments, completely revising the earlier views about the fracture-induced electromagnetic emissions.

Electromagnetic induction sensor for dynamic testing of coagulation process.

PubMed

Wang, Zhe; Yu, Yuanhua; Yu, Zhanjiang; Chen, Qimeng

2018-03-01

With the increasing demand for coagulation POCT for patients in the surgery department or the ICU, rapid coagulation testing techniques and methods have drawn widespread attention from scholars and businessmen. This paper proposes the use of electromagnetic induction sensor probe for detection of dynamic process causing changes in the blood viscosity and density before and after coagulation based on the damped vibration principle, in order to evaluate the coagulation status. Utilizing the dynamic principle, the differential equation of vibration system comprising elastic support and electromagnetic induction device is established through sensor dynamic modeling. The structural parameters of elastic support are optimized, and the circular sheet spring is designed. Furthermore, harmonic response analysis and vibration fatigue coupling analysis are performed on the elastic support of the sensor by considering the natural frequency of the system, and the electromagnetic induction sensor testing device is set up. Using the device and coagulation reagent, the standard curve for coagulation POCT is plotted, and the blood sample application in clinical patients is established, which are methodologically compared with the imported POCT coagulation analyzer. The results show that the sensor designed in this paper has a first-order natural frequency of 11.368 Hz, which can withstand 5.295 × 10 2 million times of compressions and rebounds. Its correlation with the results of SONOCLOT analyzer reaches 0.996, and the reproducibility 0.002. The electromagnetic induction coagulation testing sensor designed has good elasticity and anti-fatigue, which can meet the accuracy requirement of clinical detection. This study provides the core technology for developing the electromagnetic induction POCT instrument for dynamic testing of coagulation process.

Space Shuttle Flight Support Motor no. 1 (FSM-1)

NASA Technical Reports Server (NTRS)

Hughes, Phil D.

1990-01-01

Space Shuttle Flight Support Motor No. 1 (FSM-1) was static test fired on 15 Aug. 1990 at the Thiokol Corporation Static Test Bay T-24. FSM-1 was a full-scale, full-duration static test fire of a redesigned solid rocket motor. FSM-1 was the first of seven flight support motors which will be static test fired. The Flight Support Motor program validates components, materials, and manufacturing processes. In addition, FSM-1 was the full-scale motor for qualification of Western Electrochemical Corporation ammonium perchlorate. This motor was subjected to all controls and documentation requirements CTP-0171, Revision A. Inspection and instrumentation data indicate that the FSM-1 static test firing was successful. The ambient temperature during the test was 87 F and the propellant mean bulk temperature was 82 F. Ballistics performance values were within the specified requirements. The overall performance of the FSM-1 components and test equipment was nominal.

Full PIC simulations of solar radio emission

NASA Astrophysics Data System (ADS)

Sgattoni, A.; Henri, P.; Briand, C.; Amiranoff, F.; Riconda, C.

2017-12-01

Solar radio emissions are electromagnetic (EM) waves emitted in the solar wind plasma as a consequence of electron beams accelerated during solar flares or interplanetary shocks such as ICMEs. To describe their origin, a multi-stage model has been proposed in the 60s which considers a succession of non-linear three-wave interaction processes. A good understanding of the process would allow to infer the kinetic energy transfered from the electron beam to EM waves, so that the radio waves recorded by spacecraft can be used as a diagnostic for the electron beam.Even if the electrostatic problem has been extensively studied, full electromagnetic simulations were attempted only recently. Our large scale 2D-3V electromagnetic PIC simulations allow to identify the generation of both electrostatic and EM waves originated by the succession of plasma instabilities. We tested several configurations varying the electron beam density and velocity considering a background plasma of uniform density. For all the tested configurations approximately 105 of the electron-beam kinetic energy is transfered into EM waves emitted in all direction nearly isotropically. With this work we aim to design experiments of laboratory astrophysics to reproduce the electromagnetic emission process and test its efficiency.

Interference Processes During Reradiation of Attosecond Pulses of Electromagnetic Field by Graphene

NASA Astrophysics Data System (ADS)

Makarov, D. N.; Matveev, V. I.; Makarova, K. A.

2018-05-01

Interference spectra during reradiation of attosecond pulses of electromagnetic field by graphene sheets are considered. Analytical expressions for calculations of spectral distributions are derived. As an example, the interference spectra of a graphene sheet and a flat rectangular lattice are compared.

Use of an Electromagnetic Seepage Meter to Investigate Temporal Variability in Lake Seepage

USGS Publications Warehouse

Rosenberry, D.O.; Morin, R.H.

2004-01-01

A commercially available electromagnetic flowmeter is attached to a seepage cylinder to create an electromagnetic seepage meter (ESM) for automating measurement of fluxes across the sediment/water interface between ground water and surface water. The ESM is evaluated through its application at two lakes in New England, one where water seeps into the lake and one where water seeps out of the lake. The electromagnetic flowmeter replaces the seepage-meter bag and provides a continuous series of measurements from which temporal seepage processes can be investigated. It provides flow measurements over a range of three orders of magnitude, and contains no protruding components or moving parts. The ESM was used to evaluate duration of seepage disturbance following meter installation and indicated natural seepage rates resumed approximately one hour following meter insertion in a sandy lakebed. Lakebed seepage also varied considerably in response to lakebed disturbances, near-shore waves, and rain-falls, indicating hydrologic processes are occurring in shallow lakebed settings at time scales that have largely gone unobserved.

Avionics system design for high energy fields: A guide for the designer and airworthiness specialist

NASA Technical Reports Server (NTRS)

Mcconnell, Roger A.

1987-01-01

Because of the significant differences in transient susceptibility, the use of digital electronics in flight critical systems, and the reduced shielding effects of composite materials, there is a definite need to define pracitices which will minimize electromagnetic susceptibility, to investigate the operational environment, and to develop appropriate testing methods for flight critical systems. The design practices which will lead to reduced electromagnetic susceptibility of avionics systems in high energy fields is described. The levels of emission that can be anticipated from generic digital devices. It is assumed that as data processing equipment becomes an ever larger part of the avionics package, the construction methods of the data processing industry will increasingly carry over into aircraft. In Appendix 1 tentative revisions to RTCA DO-160B, Environmental Conditions and Test Procedures for Airborne Equipment, are presented. These revisions are intended to safeguard flight critical systems from the effects of high energy electromagnetic fields. A very extensive and useful bibliography on both electromagnetic compatibility and avionics issues is included.

Use of Permanent Magnets in Electromagnetic Facilities for the Treatment of Aluminum Alloys

NASA Astrophysics Data System (ADS)

Beinerts, Toms; Bojarevičs, Andris; Bucenieks, Imants; Gelfgat, Yuri; Kaldre, Imants

2016-06-01

The possibility of applying the electromagnetic induction pump with permanent magnets for the transportation and stirring of aluminum melts in metallurgical furnaces is investigated. The electromagnetic and hydraulic characteristics of the pump have been investigated theoretically and experimentally with regard to its position in the furnace. The results of the experiments performed with a model in a eutectic InGaSn melt are in good agreement with the calculation data. Extrapolation of the experimental results on the physical characteristics of aluminum melts allows recommending such pumps for contactless control of motion and heat/mass transfer in aluminum melts in different technological processes. A high temperature and the aggressive properties of aluminum alloys make it complicated to use different mechanical devices to solve technological problems, such as liquid metal transportation, dosing, stirring, etc. In this case, any device units or elements moving in or contacting with the melt suffer from corrosion polluting the melt. Therefore, of more importance and topicality are contactless electromagnetic methods for processing of molten metals.

Use of an electromagnetic seepage meter to investigate temporal variability in lake seepage.

PubMed

Rosenberry, Donald O; Morin, Roger H

2004-01-01

A commercially available electromagnetic flowmeter is attached to a seepage cylinder to create an electromagnetic seepage meter (ESM) for automating measurement of fluxes across the sediment/water interface between ground water and surface water. The ESM is evaluated through its application at two lakes in New England, one where water seeps into the lake and one where water seeps out of the lake. The electromagnetic flowmeter replaces the seepage-meter bag and provides a continuous series of measurements from which temporal seepage processes can be investigated. It provides flow measurements over a range of three orders of magnitude, and contains no protruding components or moving parts. The ESM was used to evaluate duration of seepage disturbance following meter installation and indicated natural seepage rates resumed approximately one hour following meter insertion in a sandy lakebed. Lakebed seepage also varied considerably in response to lakebed disturbances, near-shore waves, and rainfalls, indicating hydrologic processes are occurring in shallow lakebed settings at time scales that have largely gone unobserved.

Analysis of electromagnetic interference from power system processing and transmission components for Space Station Freedom

NASA Technical Reports Server (NTRS)

Barber, Peter W.; Demerdash, Nabeel A. O.; Hurysz, B.; Luo, Z.; Denny, Hugh W.; Millard, David P.; Herkert, R.; Wang, R.

1992-01-01

The goal of this research project was to analyze the potential effects of electromagnetic interference (EMI) originating from power system processing and transmission components for Space Station Freedom. The approach consists of four steps: (1) developing analytical tools (models and computer programs); (2) conducting parameterization (what if?) studies; (3) predicting the global space station EMI environment; and (4) providing a basis for modification of EMI standards.

Containerless Processing on ISS: Ground Support Program for EML

NASA Technical Reports Server (NTRS)

Diefenbach, Angelika; Schneider, Stephan; Willnecker, Rainer

2012-01-01

EML is an electromagnetic levitation facility planned for the ISS aiming at processing and investigating liquid metals or semiconductors by using electromagnetic levitation technique under microgravity with reduced electromagnetic fields and convection conditions. Its diagnostics and processing methods allow to measure thermophysical properties in the liquid state over an extended temperature range and to investigate solidification phenomena in undercooled melts. The EML project is a common effort of The European Space Agency (ESA) and the German Space Agency DLR. The Microgravity User Support Centre MUSC at Cologne, Germany, has been assigned the responsibility for EML operations. For the EML experiment preparation an extensive scientific ground support program is established at MUSC, providing scientific and technical services in the preparation, performance and evaluation of the experiments. Its final output is the transcription of the scientific goals and requirements into validated facility control parameters for the experiment execution onboard the ISS.

The Firework of Electromagnetic Counterparts from GW170817

NASA Astrophysics Data System (ADS)

Siegel, Daniel

2018-01-01

The gravitational-wave signal of the binary neutron star merger GW170817 was followed by a firework of electromagnetic transients across the entire electromagnetic spectrum. The gamma-ray emission has provided strong evidence for the association of short gamma-ray bursts (SGRBs) with binary neutron star mergers and the ultraviolet, optical, and near-infrared emission is consistent with a kilonova indicative of the formation of heavy elements in the merger ejecta by the rapid neutron capture process (r-process). In this talk, I will discuss and review theoretical scenarios to interpret the gamma-ray, X-ray, and radio observations. I will present recent results from general-relativistic magnetohydrodynamic simulations and discuss possible scenarios and mass ejection mechanisms that can give rise to the observed kilonova features. In particular, I will argue that massive winds from neutrino-cooled post-merger accretion disks most likely synthesized the heavy r-process elements in GW170817.

Classical electromagnetic radiation of the Dirac electron

NASA Technical Reports Server (NTRS)

Lanyi, G.

1973-01-01

A wave-function-dependent four-vector potential is added to the Dirac equation in order to achieve conservation of energy and momentum for a Dirac electron and its emitted electromagnetic field. The resultant equation contains solutions which describe transitions between different energy states of the electron. As a consequence it is possible to follow the space-time evolution of such a process. This evolution is shown in the case of the spontaneous emission of an electromagnetic field by an electron bound in a hydrogen-like atom. The intensity of the radiation and the spectral distribution are calculated for transitions between two eigenstates. The theory gives a self-consistent deterministic description of some simple radiation processes without using quantum electrodynamics or the correspondence principle.

[INVITED] Coherent perfect absorption of electromagnetic wave in subwavelength structures

NASA Astrophysics Data System (ADS)

Yan, Chao; Pu, Mingbo; Luo, Jun; Huang, Yijia; Li, Xiong; Ma, Xiaoliang; Luo, Xiangang

2018-05-01

Electromagnetic (EM) absorption is a common process by which the EM energy is transformed into other kinds of energy in the absorber, for example heat. Perfect absorption of EM with structures at subwavelength scale is important for many practical applications, such as stealth technology, thermal control and sensing. Coherent perfect absorption arises from the interplay of interference and absorption, which can be interpreted as a time-reversed process of lasing or EM emitting. It provides a promising way for complete absorption in both nanophotonics and electromagnetics. In this review, we discuss basic principles and properties of a coherent perfect absorber (CPA). Various subwavelength structures including thin films, metamaterials and waveguide-based structures to realize CPAs are compared. We also discuss the potential applications of CPAs.

Simultaneous Noncontact Precision Imaging of Microstructural and Thickness Variation in Dielectric Materials Using Terahertz Energy

NASA Technical Reports Server (NTRS)

Roth, Donald J (Inventor)

2011-01-01

A process for simultaneously measuring the velocity of terahertz electromagnetic radiation in a dielectric material sample without prior knowledge of the thickness of the sample and for measuring the thickness of a material sample using terahertz electromagnetic radiation in a material sample without prior knowledge of the velocity of the terahertz electromagnetic radiation in the sample is disclosed and claimed. The process evaluates, in a plurality of locations, the sample for microstructural variations and for thickness variations and maps the microstructural and thickness variations by location. A thin sheet of dielectric material may be used on top of the sample to create a dielectric mismatch. The approximate focal point of the radiation source (transceiver) is initially determined for good measurements.

Non-linear processes in the Earth atmosphere boundary layer

NASA Astrophysics Data System (ADS)

Grunskaya, Lubov; Valery, Isakevich; Dmitry, Rubay

2013-04-01

The work is connected with studying electromagnetic fields in the resonator Earth-Ionosphere. There is studied the interconnection of tide processes of geophysical and astrophysical origin with the Earth electromagnetic fields. On account of non-linear property of the resonator Earth-Ionosphere the tides (moon and astrophysical tides) in the electromagnetic Earth fields are kinds of polyharmonic nature. It is impossible to detect such non-linear processes with the help of the classical spectral analysis. Therefore to extract tide processes in the electromagnetic fields, the method of covariance matrix eigen vectors is used. Experimental investigations of electromagnetic fields in the atmosphere boundary layer are done at the distance spaced stations, situated on Vladimir State University test ground, at Main Geophysical Observatory (St. Petersburg), on Kamchatka pen., on Lake Baikal. In 2012 there was continued to operate the multichannel synchronic monitoring system of electrical and geomagnetic fields at the spaced apart stations: VSU physical experimental proving ground; the station of the Institute of Solar and Terrestrial Physics of Russian Academy of Science (RAS) at Lake Baikal; the station of the Institute of volcanology and seismology of RAS in Paratunka; the station in Obninsk on the base of the scientific and production society "Typhoon". Such investigations turned out to be possible after developing the method of scanning experimental signal of electromagnetic field into non- correlated components. There was used a method of the analysis of the eigen vectors ofthe time series covariance matrix for exposing influence of the moon tides on Ez. The method allows to distribute an experimental signal into non-correlated periodicities. The present method is effective just in the situation when energetical deposit because of possible influence of moon tides upon the electromagnetic fields is little. There have been developed and realized in program components in the form of PAS instruments of processes of geophysical and man-triggered nature; to predict the presence of the features of geophysical nature in the electromagnetic field of the atmosphere boundary surface layer; to study dynamics the analyzed signals coming from the geophysical and man-triggered sources in the electrical and magnetic fields of the atmosphere boundary surface layer; to expose changes of the investigated time series in the periods preceding the appearance of the predicted phenomena; to form clusters of the time series being the features of the predicted events. On the base of the exposed clusters of the time series there have been built the predicting rules allowing to coordinate the probability of appearing the groups of the occurred events. The work is carried out with supporting of Program FPP #14.B37.210668, FPP #5.2071.2011, RFBR #11-05-97518.

Energy and technology review: Engineering modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cabayan, H.S.; Goudreau, G.L.; Ziolkowski, R.W.

1986-10-01

This report presents information concerning: Modeling Canonical Problems in Electromagnetic Coupling Through Apertures; Finite-Element Codes for Computing Electrostatic Fields; Finite-Element Modeling of Electromagnetic Phenomena; Modeling Microwave-Pulse Compression in a Resonant Cavity; Lagrangian Finite-Element Analysis of Penetration Mechanics; Crashworthiness Engineering; Computer Modeling of Metal-Forming Processes; Thermal-Mechanical Modeling of Tungsten Arc Welding; Modeling Air Breakdown Induced by Electromagnetic Fields; Iterative Techniques for Solving Boltzmann's Equations for p-Type Semiconductors; Semiconductor Modeling; and Improved Numerical-Solution Techniques in Large-Scale Stress Analysis.

Electromagnetic tornadoes in space. Ion conics along auroral field lines generated by lower hybrid waves and electromagnetic turbulence in the ion-cyclotron range of frequencies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, T.; Crew, G.B.; Retterer, J.M.

1988-01-01

The exotic phenomenon of energetic ion-conic formation by plasma waves in the magnetosphere is considered. Two particular transverse heating mechanisms are reviewed in detail: lower-hybrid energization of ions in the boundary layer of the plasma sheet, and electromagnetic ion cyclotron resonance heating in the central region of the plasma sheet. Mean particle calculations, plasma simulations, and analytical treatments of the heating processes are described.

Numerical simulation of the early-time high altitude electromagnetic pulse

NASA Astrophysics Data System (ADS)

Meng, Cui; Chen, Yu-Sheng; Liu, Shun-Kun; Xie, Qin-Chuan; Chen, Xiang-Yue; Gong, Jian-Cheng

2003-12-01

In this paper, the finite difference method is used to develop the Fortran software MCHII. The physical process in which the electromagnetic signal is generated by the interaction of nuclear-explosion-induced Compton currents with the geomagnetic field is numerically simulated. The electromagnetic pulse waveforms below the burst point are investigated. The effects of the height of burst, yield and the time-dependence of gamma-rays are calculated by using the MCHII code. The results agree well with those obtained by using the code CHAP.

ALTERATIONS IN CALCIUM ION ACTIVITY BY ELF AND RF ELECTROMAGNETIC FIELDS

EPA Science Inventory

Alterations in calcium ion activity by ELF and RF electromagnetic fields

Introduction

Calcium ions play many important roles in biological systems. For example, calcium ion activity can be used as an indicator of second-messenger signal-transduction processe...

Electromagnetic Treatment of Loblolly Pine Seeds

Treesearch

James P. Barnett; Stanley L. Krugman

1989-01-01

Loblolly pine (Pinus taeda L.) seeds were exposed to an electromagnetic radiation treatment (Energy Transfer Process, marketed by the Energy Transfer Corporation), and the effects of the treatments on seed germination, seedling development, disease resistance, and field performance of seedlings were evaluated. None of the evaluated variables showed...

The Dynamic Multi-objective Multi-vehicle Covering Tour Problem

DTIC Science & Technology

2013-06-01

AI Artificial Intelligence AUV Autonomous Underwater Vehicle CLP Clover Leaf Problem CSP Covering Salesman Problem CTP Covering Tour Problem CVRP...introduces a new formalization - the DMOMCTP. Related works from routing problems, Artificial Intelligence ( AI ), and MOPs are discussed briefly. As a...the rest of that framework being replaced. The codebase differs from jMetal 4.2 in that it can handle the time and DM dependent nature of the DMOMCTP

Summary of JAYGO mixing and FSM-1 application of castable inhibitor and liner

NASA Technical Reports Server (NTRS)

Evans, Kurt B.

1990-01-01

Two JAYGO planetary mixers (12 and 42 gallon) are being qualified to mix STW5-3224 liner and STW5-3223 castable inhibitor. These mixers are an integral part of a mix process which allows for safe addition of the asbestos component. An essential part of the engineering evaluation (ETP-0347) of these mixers is the generation of static test fire data. Ultimately, these results will help confirm the adequacy of these mixers for production mixing of liner and inhibitor. (These data are not required for qualification of the Certification Test Plan CTP-0125). The details on the mixing, inhibiting, and sling-lining of JAYGO-mixed castable inhibitor and liner which were applied to the FSM-1 segments are presented. The objectives are the following: (1) to document processing events surrounding the JAYO mixing of castable inhibitor and liner, and the subsequent inhibiting and sling lining onto the FSM-1 segments; and (2) to substantiate the measured properties of these JAYGO-mixed materials (rheological and mechanical) and compare these properties to existing production database.

Genome hypermethylation in Pinus silvestris of Chernobyl--a mechanism for radiation adaptation?

PubMed

Kovalchuk, Olga; Burke, Paula; Arkhipov, Andrey; Kuchma, Nikolaj; James, S Jill; Kovalchuk, Igor; Pogribny, Igor

2003-08-28

Adaptation is a complex process by which populations of organisms respond to long-term environmental stresses by permanent genetic change. Here we present data from the natural "open-field" radiation adaptation experiment after the Chernobyl accident and provide the first evidence of the involvement of epigenetic changes in adaptation of a eukaryote-Scots pine (Pinus silvestris), to chronic radiation exposure. We have evaluated global genome methylation of control and radiation-exposed pine trees using a method based on cleavage by a methylation-sensitive HpaII restriction endonuclease that leaves a 5' guanine overhang and subsequent single nucleotide extension with labeled [3H] dCTP. We have found that genomic DNA of exposed pine trees was considerably hypermethylated. Moreover, hypermethylation appeared to be dependent upon the radiation dose absorbed by the trees. Such hypermethylation may be viewed as a defense strategy of plants that prevents genome instability and reshuffling of the hereditary material, allowing survival in an extreme environment. Further studies are clearly needed to analyze in detail the involvement of DNA methylation and other epigenetic mechanisms in the complex process of radiation stress and adaptive response.

The importance of salivary cortisol in the diagnosis of adrenal insufficiency in cirrhosis.

PubMed

Araz, Filiz; Soydaş, Barış; Özer, Birol; Serin, Ender

2016-05-01

Reports on adrenal insufficiency (AI) are unexpectedly high in cirrhosis, and the diagnosis of this condition remains a challenge. We aimed to define the prevalence rate of AI in stable cirrhotic patients and determine the correlations of free cortisol and salivary cortisol with total cortisol. Between January 2011 and September 2011, 110 consecutive cirrhotic patients without any infection or hemodynamic instability were enrolled. Baseline total and salivary cortisol levels were measured. The free cortisol level was calculated according to the Coolens' formula. Post-stimulation total and salivary cortisol levels were measured, and the free cortisol level was recalculated. The mean age of the patients was 62.1±11.4 years. There were 54 males (49.1%). The mean Child-Turcotte-Pugh (CTP) score was 7.2±2.3. Twenty-two (20%) patients were at the CTP-C level. AI was present in 23 (20.9%) and 17 (15.5%) of all patients according to the total and free cortisol criteria, respectively. For basal and stimulated levels, salivary cortisol rather than total cortisol correlates well with free cortisol. The diagnosis of AI on the basis of total cortisol measurement overestimates the prevalence of AI in cirrhosis. Salivary cortisol, which correlates well with free cortisol, is a promising alternative for the diagnosis of AI in cirrhotic patients.

Regulation of CTP Synthase Filament Formation During DNA Endoreplication in Drosophila.

PubMed

Wang, Pei-Yu; Lin, Wei-Cheng; Tsai, Yi-Cheng; Cheng, Mei-Ling; Lin, Yu-Hung; Tseng, Shu-Heng; Chakraborty, Archan; Pai, Li-Mei

2015-12-01

CTP synthase (CTPsyn) plays an essential role in DNA, RNA, and lipid synthesis. Recent studies in bacteria, yeast, and Drosophila all reveal a polymeric CTPsyn structure, which dynamically regulates its enzymatic activity. However, the molecular mechanism underlying the formation of CTPsyn polymers is not completely understood. In this study, we found that reversible ubiquitination regulates the dynamic assembly of the filamentous structures of Drosophila CTPsyn. We further determined that the proto-oncogene Cbl, an E3 ubiquitin ligase, controls CTPsyn filament formation in endocycles. While the E3 ligase activity of Cbl is required for CTPsyn filament formation, Cbl does not affect the protein levels of CTPsyn. It remains unclear whether the regulation of CTPsyn filaments by Cbl is through direct ubiquitination of CTPsyn. In the absence of Cbl or with knockdown of CTPsyn, the progression of the endocycle-associated S phase was impaired. Furthermore, overexpression of wild-type, but not enzymatically inactive CTPsyn, rescued the endocycle defect in Cbl mutant cells. Together, these results suggest that Cbl influences the nucleotide pool balance and controls CTPsyn filament formation in endocycles. This study links Cbl-mediated ubiquitination to the polymerization of a metabolic enzyme and reveals a role for Cbl in endocycles during Drosophila development. Copyright © 2015 by the Genetics Society of America.

In Vitro Exposure Systems and Dosimetry Assessment Tools ...

EPA Pesticide Factsheets

In 2009, the passing of The Family Smoking Prevention and Tobacco Control Act facilitated the establishment of the FDA Center for Tobacco Products (CTP) and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed “modified risk”. On 4-6 April 2016, the Institute for In Vitro Sciences, Inc. (IIVS) convened a workshop conference titled “In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products” to bring together stakeholders representing regulatory agencies, academia, and industry to address the research priorities articulated by the FDA CTP. Specific topics were covered to assess the status of current in vitro smoke and aerosol/vapor exposure systems, as well as the various approaches and challenges to quantifying the complex exposures, in in vitro pulmonary models developed for evaluating adverse pulmonary events resulting from tobacco product exposures. The four core topics covered were, 1) Tobacco Smoke And E-Cigarette Aerosols, 2) Air-Liquid Interface-In Vitro Exposure Systems, 3) Dosimetry Approaches For Particles And Vapors; In Vitro Dosimetry Determinations and 4) Exposure Microenvironment/Physiology Of Cells. The two and a half day workshop included presentations from 20 expert speakers, poster sessions, networking discussions, and breakout sessions which identified key findings and provided recommendations to advance these technologies. Here, we will re

Progress with infliximab biosimilars for inflammatory bowel disease.

PubMed

Kurti, Zsuzsanna; Gonczi, Lorant; Lakatos, Peter L

2018-04-29

Biological therapies have revolutionized the treatment of inflammatory bowel diseases (IBD) in the last two decades. Though biological drugs are effective, their use is associated with high costs and access to biological agents varies among countries. As the patent for the reference products expired, the advent of biosimilar monoclonal antibodies has been expected. Biosimilars represent less expensive alternatives compared to the reference product. Areas covered: In this review, authors will review the literature on the clinical efficacy, safety and immunogenicity of current and future biosimilar infliximabs. Short- and medium-term data from real-life cohorts and from randomized-clinical trials in IBD demonstrated similar outcomes in terms of efficacy, safety and immunogenicity as the reference product for CT-P13. Switch data from the reference to the biosimilar product are also accumulating (including the NOR-SWITCH and the CT-P13 3.4 study). Expert opinion: The use of biosimilar infliximab in IBD is increasing worldwide. Its use may be associated with budget savings leading to better access to biological therapies and consequently improved health outcomes. Switching from the originator to a biosimilar in patients with IBD is acceptable, although scientific and clinical evidence is lacking regarding reverse switching, multiple switching, and cross-switching among biosimilars in IBD patients.

Non-HFE iron overload as a surrogate marker of disease severity in patients of liver cirrhosis.

PubMed

Noor, Mohd Talha; Tiwari, Manish; Kumar, Ravindra

2016-01-01

Decompensated liver cirrhosis is an important cause of mortality worldwide. Various modifiable and non-modifiable factors are involved in the pathogenesis of cirrhosis and its complications. This study was aimed to evaluate the association of iron overload and disease severity in patients of liver cirrhosis and its association with HFE gene mutation. Forty-nine patients with decompensated liver cirrhosis were recruited. Clinical and laboratory parameters were compared in patients with and without iron overload. C282Y and H63D gene mutation analysis was performed in all patients with iron overload. Iron overload was found in 20 (40.82%) patients. A significant positive correlation of transferrin saturation with Child-Turcotte-Pugh (CTP) score (r = 0.705, p < 0.001) and model for end-stage liver disease (MELD) score (r = 0.668, p < 0.001) was found. Transferrin saturation was also independently associated with high CTP and MELD score on multivariate analysis. Mortality over 3 months was significantly more common in iron-overloaded patients (p = 0.028). C282Y homozygosity or C282Y/H63D compound heterozygosity was not found in any of the patients with iron overload. Iron overload was significantly associated with disease severity and reduced survival in patients of decompensated liver cirrhosis.

Radiation dose reduction in computed tomography perfusion using spatial-temporal Bayesian methods

NASA Astrophysics Data System (ADS)

Fang, Ruogu; Raj, Ashish; Chen, Tsuhan; Sanelli, Pina C.

2012-03-01

In current computed tomography (CT) examinations, the associated X-ray radiation dose is of significant concern to patients and operators, especially CT perfusion (CTP) imaging that has higher radiation dose due to its cine scanning technique. A simple and cost-effective means to perform the examinations is to lower the milliampere-seconds (mAs) parameter as low as reasonably achievable in data acquisition. However, lowering the mAs parameter will unavoidably increase data noise and degrade CT perfusion maps greatly if no adequate noise control is applied during image reconstruction. To capture the essential dynamics of CT perfusion, a simple spatial-temporal Bayesian method that uses a piecewise parametric model of the residual function is used, and then the model parameters are estimated from a Bayesian formulation of prior smoothness constraints on perfusion parameters. From the fitted residual function, reliable CTP parameter maps are obtained from low dose CT data. The merit of this scheme exists in the combination of analytical piecewise residual function with Bayesian framework using a simpler prior spatial constrain for CT perfusion application. On a dataset of 22 patients, this dynamic spatial-temporal Bayesian model yielded an increase in signal-tonoise-ratio (SNR) of 78% and a decrease in mean-square-error (MSE) of 40% at low dose radiation of 43mA.

Prevention of neural hypersensitivity after acute upper limb burns: Development and pilot of a cortical training protocol.

PubMed

Edgar, Dale; Zorzi, Lisa M; Wand, Ben M; Brockman, Nathalie; Griggs, Carolyn; Clifford, Matthew; Wood, Fiona

2011-06-01

Acute burn patients suffer pain and secondary hyperalgesia. This alters movement patterns and impairs function. Non-pharmacological methods of treatment are limited and lack rigorous testing and evidence for use. The treatment in this case series was designed to direct conscious attention to, and normalise sensation of, the injured limb in pain free way. The aim of the study was to describe a cortical training programme (CTP) in acute upper limb burn patients and to investigate the efficacy, safety and feasibility of the protocol. The study is a descriptive case series (n=6). Study tasks engaged sensory and motor nerves to influence the perception of the injured area. Visual and tactile inputs to maintain and, or normalise the homuncular map were central to the intervention. One patient, who commenced the study without resting pain, responded negatively. The remaining five patients had reduced pain and fear avoidance behaviours with associated improvement in arm function. The CTP approach is safe and feasible for use with acute burn patients where pain is reported at rest. Comparative studies are required to determine the relative efficacy of the program to usual interventions and the patients who may benefit from the technique. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

[DNA microarray reveals changes in gene expression of endothelial cells under shear stress].

PubMed

Cheng, Min; Zhang, Wensheng; Chen, Huaiqing; Wu, Wenchao; Huang, Hua

2004-04-01

cDNA microarray technology is used as a powerful tool for rapid, comprehensive, and quantitative analysis of gene profiles of cultured human umbilical vein endothelial cells(HUVECs) in the normal static group and the shear stressed (4.20 dyne/cm2, 2 h) group. The total RNA from normal static cultured HUVECs was labeled by Cy3-dCTP, and total RNA of HUVECs from the paired shear stressed experiment was labeled by Cy5-dCTP. The expression ratios reported are the average from the two separate experiments. After bioinformatics analysis, we identified a total of 108 genes (approximately 0.026%) revealing differential expression. Of these 53 genes expressions were up-regulated, the most enhanced ones being human homolog of yeast IPP isomerase, human low density lipoprotein receptor gene, Squalene epoxidase gene, 7-dehydrocholesterol reductase, and 55 were down-regulated, the most decreased ones being heat shock 70 kD protein 1, TCB gene encoding cytosolic thyroid hormone-binding protein in HUVECs exposed to low shear stress. These results indicate that the cDNA microarray technique is effective in screening the differentially expressed genes in endothelial cells induced by various experimental conditions and the data may serve as stimuli to further researches.

Identification of cytidine-5-triphosphate synthase1-selective inhibitory peptide from random peptide library displayed on T7 phage.

PubMed

Sakamoto, Kotaro; Ishibashi, Yoshihiro; Adachi, Ryutaro; Matsumoto, Shin-Ichi; Oki, Hideyuki; Kamada, Yusuke; Sogabe, Satoshi; Zama, Yumi; Sakamoto, Jun-Ichi; Tani, Akiyoshi

2017-08-01

Cytidine triphosphate synthase 1 (CTPS1) is an enzyme expressed in activated lymphocytes that catalyzes the conversion of uridine triphosphate (UTP) to cytidine triphosphate (CTP) with ATP-dependent amination, using either L-glutamine or ammonia as the nitrogen source. Since CTP plays an important role in DNA/RNA synthesis, phospholipid synthesis, and protein sialyation, CTPS1-inhibition is expected to control lymphocyte proliferation and size expansion in inflammatory diseases. In contrast, CTPS2, an isozyme of CTPS1 possessing 74% amino acid sequence homology, is expressed in normal lymphocytes. Thus, CTPS1-selective inhibition is important to avoid undesirable side effects. Here, we report the discovery of CTpep-3: Ac-FRLGLLKAFRRLF-OH from random peptide libraries displayed on T7 phage, which exhibited CTPS1-selective binding with a K D value of 210nM in SPR analysis and CTPS1-selective inhibition with an IC 50 value of 110nM in the enzyme assay. Furthermore, two fundamentally different approaches, enzyme inhibition assay and HDX-MS, provided the same conclusion that CTpep-3 acts by binding to the amidoligase (ALase) domain on CTPS1. To our knowledge, CTpep-3 is the first CTPS1-selective inhibitor. Copyright © 2017 Elsevier Inc. All rights reserved.

Study of a Single-Power Two-Circuit ESR Process with Current-Carrying Mold: Mathematical Simulation of the Process and Experimental Verification

NASA Astrophysics Data System (ADS)

Dong, Yanwu; Hou, Zhiwen; Jiang, Zhouhua; Cao, Haibo; Feng, Qianlong; Cao, Yulong

2018-02-01

A novel single-power two-circuit ESR process (ESR-STCCM) with current-carrying mold has been investigated via numerical simulation and experimental research in this paper. A 2D quasi-steady-state mathematical model is developed to describe ESR-STCCM. The electromagnetic field, flow field, slag pool temperature distribution, and the shape of a molten steel pool in ESR-STCCM have been investigated by FLUENT software as well as user-defined functions (UDF). The results indicate that ESR-STCCM is different from the conventional ESR process. The maximum electromagnetic force, current density, Joule heat, and slag pool flow velocity are located in the lower part of the conductor in the ESR-STCCM process. The direction of the maximum electromagnetic force inclines upward. There are two distinct vortices in the slag pool. The larger swirl rotates counterclockwise near the conductor, with a value of 0.0263 m s-1 due to the interaction of the electromagnetic force and gravity. The maximum temperature of the slag pool is 2070 K (1797 °C) and is located in the center of the swirl with a filling ratio of 0.6 and a 20 mm electrode immersion depth. The depth of a molten steel pool is shallower, which is conducive to improving solidification quality. In addition, the filling ratio of 0.6 is conducive to controlling steel solidification quality. Some experiments have been done, and the numerical model is confirmed by experimental results.

Narrow field electromagnetic sensor system and method

DOEpatents

McEwan, Thomas E.

1996-01-01

A narrow field electromagnetic sensor system and method of sensing a characteristic of an object provide the capability to realize a characteristic of an object such as density, thickness, or presence, for any desired coordinate position on the object. One application is imaging. The sensor can also be used as an obstruction detector or an electronic trip wire with a narrow field without the disadvantages of impaired performance when exposed to dirt, snow, rain, or sunlight. The sensor employs a transmitter for transmitting a sequence of electromagnetic signals in response to a transmit timing signal, a receiver for sampling only the initial direct RF path of the electromagnetic signal while excluding all other electromagnetic signals in response to a receive timing signal, and a signal processor for processing the sampled direct RF path electromagnetic signal and providing an indication of the characteristic of an object. Usually, the electromagnetic signal is a short RF burst and the obstruction must provide a substantially complete eclipse of the direct RF path. By employing time-of-flight techniques, a timing circuit controls the receiver to sample only the initial direct RF path of the electromagnetic signal while not sampling indirect path electromagnetic signals. The sensor system also incorporates circuitry for ultra-wideband spread spectrum operation that reduces interference to and from other RF services while allowing co-location of multiple electronic sensors without the need for frequency assignments.

Narrow field electromagnetic sensor system and method

DOEpatents

McEwan, T.E.

1996-11-19

A narrow field electromagnetic sensor system and method of sensing a characteristic of an object provide the capability to realize a characteristic of an object such as density, thickness, or presence, for any desired coordinate position on the object. One application is imaging. The sensor can also be used as an obstruction detector or an electronic trip wire with a narrow field without the disadvantages of impaired performance when exposed to dirt, snow, rain, or sunlight. The sensor employs a transmitter for transmitting a sequence of electromagnetic signals in response to a transmit timing signal, a receiver for sampling only the initial direct RF path of the electromagnetic signal while excluding all other electromagnetic signals in response to a receive timing signal, and a signal processor for processing the sampled direct RF path electromagnetic signal and providing an indication of the characteristic of an object. Usually, the electromagnetic signal is a short RF burst and the obstruction must provide a substantially complete eclipse of the direct RF path. By employing time-of-flight techniques, a timing circuit controls the receiver to sample only the initial direct RF path of the electromagnetic signal while not sampling indirect path electromagnetic signals. The sensor system also incorporates circuitry for ultra-wideband spread spectrum operation that reduces interference to and from other RF services while allowing co-location of multiple electronic sensors without the need for frequency assignments. 12 figs.

Current status of the real-time processing of complex radar signatures

NASA Astrophysics Data System (ADS)

Clay, E.

The real-time processing technique developed by ONERA to characterize radar signatures at the Brahms station is described. This technique is used for the real-time analysis of the RCS of airframes and rotating parts, the one-dimensional tomography of aircraft, and the RCS of electromagnetic decoys. Using this technique, it is also possible to optimize the experimental parameters, i.e., the analysis band, the microwave-network gain, and the electromagnetic window of the analysis.

Investigation of Electromagnetic Signatures of a FPGA Using an APREL EM-ISIGHT System

DTIC Science & Technology

2015-12-01

unprofessional workmanship in the bonding process. Focused ion beam (FIB) images often consist of some type of etch and/or deposition of material from/to...characteristics of conducted emissions." Electromagnetic Compatibility, 2008. EMC 2008. IEEE International Symposium (2008): 1-4. Montanari, Ivan

The influence of electromagnetic radiation generated by a mobile phone on the skeletal system of rats.

PubMed

Sieroń-Stołtny, Karolina; Teister, Łukasz; Cieślar, Grzegorz; Sieroń, Dominik; Śliwinski, Zbigniew; Kucharzewski, Marek; Sieroń, Aleksander

2015-01-01

The study was focused on the influence of electromagnetic field generated by mobile phone on the skeletal system of rats, assessed by measuring the macrometric parameters of bones, mechanical properties of long bones, calcium and phosphorus content in bones, and the concentration of osteogenesis (osteocalcin) and bone resorption (NTX, pyridinoline) markers in blood serum. The study was carried out on male rats divided into two groups: experimental group subjected to 28-day cycle of exposures in electromagnetic field of 900 MHz frequency generated by mobile phone and a control, sham-exposed one. The mobile phone-generated electromagnetic field did not influence the macrometric parameters of long bones and L4 vertebra, it altered mechanical properties of bones (stress and energy at maximum bending force, stress at fracture), it decreased the content of calcium in long bones and L4 vertebra, and it altered the concentration of osteogenesis and bone resorption markers in rats. On the basis of obtained results, it was concluded that electromagnetic field generated by 900 MHz mobile phone does not have a direct impact on macrometric parameters of bones; however, it alters the processes of bone mineralization and the intensity of bone turnover processes and thus influences the mechanical strength of bones.

The Influence of Electromagnetic Radiation Generated by a Mobile Phone on the Skeletal System of Rats

PubMed Central

Sieroń-Stołtny, Karolina; Teister, Łukasz; Cieślar, Grzegorz; Sieroń, Dominik; Śliwinski, Zbigniew; Sieroń, Aleksander

2015-01-01

The study was focused on the influence of electromagnetic field generated by mobile phone on the skeletal system of rats, assessed by measuring the macrometric parameters of bones, mechanical properties of long bones, calcium and phosphorus content in bones, and the concentration of osteogenesis (osteocalcin) and bone resorption (NTX, pyridinoline) markers in blood serum. The study was carried out on male rats divided into two groups: experimental group subjected to 28-day cycle of exposures in electromagnetic field of 900 MHz frequency generated by mobile phone and a control, sham-exposed one. The mobile phone-generated electromagnetic field did not influence the macrometric parameters of long bones and L4 vertebra, it altered mechanical properties of bones (stress and energy at maximum bending force, stress at fracture), it decreased the content of calcium in long bones and L4 vertebra, and it altered the concentration of osteogenesis and bone resorption markers in rats. On the basis of obtained results, it was concluded that electromagnetic field generated by 900 MHz mobile phone does not have a direct impact on macrometric parameters of bones; however, it alters the processes of bone mineralization and the intensity of bone turnover processes and thus influences the mechanical strength of bones. PMID:25705697

Electromagnetic processes during phase commutation in field regulated reluctance machine

NASA Astrophysics Data System (ADS)

Shishkov, A. N.; Sychev, D. A.; Zemlyansky, A. A.; Krupnova, M. N.; Funk, T. A.; Ishmet'eva, V. D.

2018-03-01

The processes of currents switching in stator windings have been explained by the existence of the electromagnetic torque ripples in the electric drive with the field-regulated reluctance machine. The maximum value of ripples in the open loop control system for the six-phase machine can reach 20 percent from the developed electromagnetic torque. This method allows one to make calculation of ripple spike towards average torque developed by the electromotor for the different number of phases. Application of a trapezoidal form of current at six phases became the solution. In case of a less number of phases than six, a ripple spike considerably increases, which is inadmissible. On the other hand, increasing the number of phases tends to the increase of the semiconductor inverter external dimensions based on the inconspicuous decreasing of a ripple spike. The creation and usage of high-speed control loops of current (HCLC) have been recommended for a reduction of the electromagnetic torque’s ripple level, as well as the appliance of positive current feedback in switching phase currents. This decision allowed one to receive a mean value of the torque more than 10%, compared to system without change, to reduce greatly ripple spike of the electromagnetic torque. The possibility of the electric drive effective operation with FRRM in emergency operation has been shown.

Development and implementation of the software for visualization and analysis of data geophysical loggers

NASA Astrophysics Data System (ADS)

Gordeev, V. F.; Malyshkov, S. Yu.; Botygin, I. A.; Sherstnev, V. S.; Sherstneva, A. I.

2017-11-01

The general trend of modern ecological geophysics is changing priorities towards rapid assessment, management and prediction of ecological and engineering soil stability as well as developing brand new geophysical technologies. The article describes researches conducted by using multi-canal geophysical logger MGR-01 (developed by IMCES SB RAS), which allows to measure flux density of very low-frequency electromagnetic radiation. It is shown that natural pulsed electromagnetic fields of the earthen lithosphere can be a source of new information on Earth's crust and processes in it, including earthquakes. The device is intended for logging electromagnetic processes in Earth's crust, geophysical exploration, finding structural and lithological inhomogeneities, monitoring the geodynamic movement of Earth's crust, express assessment of seismic hazards. The data is gathered automatically from observation point network in Siberia

Research of glass fibre used in the electromagnetic wave shielding and absorption composite material

NASA Astrophysics Data System (ADS)

Xu, M.; Jia, F.; Bao, H. Q.; Cui, K.; Zhang, F.

2016-07-01

Electromagnetic shielding and absorption composite material plays an important role in the defence and economic field. Comparing with other filler, Glass fibre and its processed product—metal-coated glass fibre can greatly reduce the material's weight and costs, while it still remains the high strength and the electromagnetic shielding effectiveness. In this paper, the electromagnetic absorption mechanism and the reflection mechanism have been investigated as a whole, and the shielding effectiveness of the double-layer glass fibre composite material is mainly focused. The relationship between the shielding effectiveness and the filled glass fibre as well as its metal-coated product's parameters has also been studied. From the subsequent coaxial flange and anechoic chamber analysis, it can be confirmed that the peak electromagnetic shielding effectiveness of this double-layer material can reach -78dB while the bandwidth is from 2GHz to 18GHz.

Storage and retrieval of electromagnetic waves with orbital angular momentum via plasmon-induced transparency.

PubMed

Bai, Zhengyang; Xu, Datang; Huang, Guoxiang

2017-01-23

We propose a scheme to realize the storage and retrieval of high-dimensional electromagnetic waves with orbital angular momentum (OAM) via plasmon-induced transparency (PIT) in a metamaterial, which consists of an array of meta-atoms constructed by a metallic structure loaded with two varactors. We show that due to PIT effect the system allows the existence of shape-preserving dark-mode plasmonic polaritons, which are mixture of electromagnetic-wave modes and dark oscillatory modes of the meta-atoms and may carry various OAMs. We demonstrate that the slowdown, storage and retrieval of multi-mode electromagnetic waves with OAMs can be achieved through the active manipulation of a control field. Our work raises the possibility for realizing PIT-based spatial multi-mode memory of electromagnetic waves and is promising for practical application of information processing with large capacity by using room-temperature metamaterials.

Evaluation of Information Leakage via Electromagnetic Emanation and Effectiveness of Tempest

NASA Astrophysics Data System (ADS)

Tanaka, Hidema

It is well known that there is relationship between electromagnetic emanation and processing information in IT devices such as personal computers and smart cards. By analyzing such electromagnetic emanation, eavesdropper will be able to get some information, so it becomes a real threat of information security. In this paper, we show how to estimate amount of information that is leaked as electromagnetic emanation. We assume the space between the IT device and the receiver is a communication channel, and we define the amount of information leakage via electromagnetic emanations by its channel capacity. By some experimental results of Tempest, we show example estimations of amount of information leakage. Using the value of channel capacity, we can calculate the amount of information per pixel in the reconstructed image. And we evaluate the effectiveness of Tempest fonts generated by Gaussian method and its threshold of security.

Scattering of Non-Relativistic Charged Particles by Electromagnetic Radiation

NASA Astrophysics Data System (ADS)

Apostol, M.

2017-11-01

The cross-section is computed for non-relativistic charged particles (like electrons and ions) scattered by electromagnetic radiation confined to a finite region (like the focal region of optical laser beams). The cross-section exhibits maxima at scattering angles given by the energy and momentum conservation in multi-photon absorption or emission processes. For convenience, a potential scattering is included and a comparison is made with the well-known Kroll-Watson scattering formula. The scattering process addressed in this paper is distinct from the process dealt with in previous studies, where the scattering is immersed in the radiation field.

Simulation of secondary emission calorimeter for future colliders

NASA Astrophysics Data System (ADS)

Yetkin, E. A.; Yetkin, T.; Ozok, F.; Iren, E.; Erduran, M. N.

2018-03-01

We present updated results from a simulation study of a conceptual sampling electromagnetic calorimeter based on secondary electron emission process. We implemented the secondary electron emission process in Geant4 as a user physics list and produced the energy spectrum and yield of secondary electrons. The energy resolution of the SEE calorimeter was σ/E = (41%) GeV1/2/√E and the response linearity to electromagnetic showers was to within 1.5%. The simulation results were also compared with a traditional scintillator calorimeter.

Monitoring cure of composite resins using frequency dependent electromagnetic sensing techniques

NASA Technical Reports Server (NTRS)

Kranbuehl, D. E.; Hoff, M. S.; Loos, A. C.; Freeman, W. T., Jr.; Eichinger, D. A.

1988-01-01

A nondestructive in situ measurement technique has been developed for monitoring and measuring the cure processing properties of composite resins. Frequency dependent electromagnetic sensors (FDEMS) were used to directly measure resin viscosity during cure. The effects of the cure cycle and resin aging on the viscosity during cure were investigated using the sensor. Viscosity measurements obtained using the sensor are compared with the viscosities calculated by the Loos-Springer cure process model. Good overall agreement was obtained except for the aged resin samples.

Gradient Structure Design of Flexible Waterborne Polyurethane Conductive Films for Ultraefficient Electromagnetic Shielding with Low Reflection Characteristic.

PubMed

Xu, Yadong; Yang, Yaqi; Yan, Ding-Xiang; Duan, Hongji; Zhao, Guizhe; Liu, Yaqing

2018-06-06

Highly efficient electromagnetic shielding materials entailing strong electromagnetic wave absorption and low reflection have become an increasing requirement for next-generation communication technologies and high-power electronic instruments. In this study, a new strategy is employed to provide flexible waterborne polyurethane composite films with an ultra-efficient electromagnetic shielding effectiveness (EMI SE) and low reflection by constructing gradient shielding layers with a magnetic ferro/ferric oxide deposited on reduced graphene oxide (rGO@Fe 3 O 4 ) and silver-coated tetraneedle-like ZnO whisker (T-ZnO/Ag) functional nanoparticles. Because of the differences in density between rGO@Fe 3 O 4 and T-ZnO/Ag, a gradient structure is automatically formed during the film formation process. The gradient distribution of rGO@Fe 3 O 4 over the whole thickness range forms an efficient electromagnetic wave absorption network that endows the film with a strong absorption ability on the top side, while a thin layer of high-density T-ZnO/Ag at the bottom constructs a highly conductive network that provides an excellent electromagnetic reflection ability for the film. This specific structure results in an "absorb-reflect-reabsorb" process when electromagnetic waves penetrate into the composite film, leading to an excellent EMI shielding performance with an extremely low reflection characteristic at a very low nanofiller content (0.8 vol % Fe 3 O 4 @rGO and 5.7 vol % T-ZnO/Ag): the EMI SE reaches 87.2 dB against the X band with a thickness of only 0.5 mm, while the shielding effectiveness of reflection (SE R ) is only 2.4 dB and the power coefficient of reflectivity ( R) is as low as 0.39. This result means that only 39% of the microwaves are reflected in the propagation process when 99.9999998% are attenuated, which is the lowest value among the reported references. This composite film with remarkable performance is suitable for application in portable and wearable smart electronics, and this method offers an effective strategy for absorption-dominated EMI shielding.

Dynamics of electronic transitions and reemission spectra of attosecond electromagnetic pulses

NASA Astrophysics Data System (ADS)

Matveev, V. I.; Makarov, D. N.

2014-05-01

The processes of reemission of attosecond electromagnetic pulses by systems in nonstationary states have been considered. The probabilities of the reemission of attosecond electromagnetic pulses at the resonance charge exchange of a proton on a hydrogen atom and at the decay of a quasistationary state, as well as the probabilities of the reemission of attosecond pulses by a system in a resonance external field, have been calculated as examples. The developed method can be applied to more complex targets, including targets in the collision state, and to various chemical reactions.

Effect exerted by a radio wave electromagnetic field on the rheological properties of water and portland-cement systems

NASA Astrophysics Data System (ADS)

Azharonok, V. V.; Belous, N. Kh.; Rodtsevich, S. P.; Koshevar, V. D.; Shkadretsova, V. G.; Goncharik, S. V.; Chubrik, N. I.; Orlovich, A. I.

2013-09-01

We have studied the effect of the regimes of high-frequency (radio wave) electromagnetic treatment of gauging water on the process of structurization and on the technological characteristics of portland-cement systems. It has been established that the radio wave electromagnetic activation of water leads to a reduction in its surface tension, dynamic viscosity, and shear stress, as well as intensifies the formation of coagulation structures in a portlandcement slurry and aids in increasing the mobility of cement-sand mixtures.

Designed electromagnetic pulsed therapy: clinical applications.

PubMed

Gordon, Glen A

2007-09-01

First reduced to science by Maxwell in 1865, electromagnetic technology as therapy received little interest from basic scientists or clinicians until the 1980s. It now promises applications that include mitigation of inflammation (electrochemistry) and stimulation of classes of genes following onset of illness and injury (electrogenomics). The use of electromagnetism to stop inflammation and restore tissue seems a logical phenomenology, that is, stop the inflammation, then upregulate classes of restorative gene loci to initiate healing. Studies in the fields of MRI and NMR have aided the understanding of cell response to low energy EMF inputs via electromagnetically responsive elements. Understanding protein iterations, that is, how they process information to direct energy, we can maximize technology to aid restorative intervention, a promising step forward over current paradigms of therapy.

Single-cycle high-intensity electromagnetic pulse generation in the interaction of a plasma wakefield with regular nonlinear structures.

PubMed

Bulanov, S S; Esirkepov, T Zh; Kamenets, F F; Pegoraro, F

2006-03-01

The interaction of regular nonlinear structures (such as subcycle solitons, electron vortices, and wake Langmuir waves) with a strong wake wave in a collisionless plasma can be exploited in order to produce ultrashort electromagnetic pulses. The electromagnetic field of the nonlinear structure is partially reflected by the electron density modulations of the incident wake wave and a single-cycle high-intensity electromagnetic pulse is formed. Due to the Doppler effect the length of this pulse is much shorter than that of the nonlinear structure. This process is illustrated with two-dimensional particle-in-cell simulations. The considered laser-plasma interaction regimes can be achieved in present day experiments and can be used for plasma diagnostics.

Multimode electromagnetic target discriminator: preliminary data results

NASA Astrophysics Data System (ADS)

Black, Christopher J.; McMichael, Ian T.; Nelson, Carl V.

2004-09-01

This paper describes the Multi-mode Electromagnetic Target Discriminator (METD) sensor and presents preliminary results from recent field experiments. The METD sensor was developed for the US Army RDECOM NVESD by The Johns Hopkins University Applied Physics Laboratory. The METD, based on the technology of the previously developed Electromagnetic Target Discriminator (ETD), is a spatial scanning electromagnetic induction (EMI) sensor that uses both the time-domain (TD) and the frequency-domain (FD) for target detection and classification. Data is collected with a custom data acquisition system and wirelessly transmitted to a base computer. We show that the METD has a high signal-to-noise ratio (SNR), the ability to detect voids created by plastic anti-tank (AT) mines, and is practical for near real-time data processing.

How can the neutrino interact with the electromagnetic field?

NASA Astrophysics Data System (ADS)

Novello, M.; Ducap, C. E. L.

2018-01-01

Maxwell electrodynamics in the fixed Minkowski space-time background can be described in an equivalent way in a curved Riemannian geometry that depends on the electromagnetic field and that we call the electromagnetic metric (e-metric for short). After showing such geometric equivalence we investigate the possibility that new processes dependent on the e-metric are allowed. In particular, for very high values of the field, a direct coupling of uncharged particles to the electromagnetic field may appear. Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), FAPERJ (Fundação do Amparo Pesquisa do Rio de Janeiro, FINEP (Financiadora de Estudos e Projetos) and Coordenação do Aperfeiçoamento do Pessoal do Ensino Superior (CAPES)

Fabrication of monodispersed nickel flower-like architectures via a solvent-thermal process and analysis of their magnetic and electromagnetic properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kong Jing; Liu Wei, E-mail: jrliu@sdu.edu.cn; Wang Fenglong

Monodispersed Ni flower-like architectures with size of 1-2 {mu}m were synthesized through a facile solvent-thermal process in 1,2-propanediol solution in the presence of polyethylene glycol (PEG) and sodium alkali for electromagnetic absorption application. The Ni architectures are composed of nanoflakes, which assemble to form three dimensional flower-like structure, and the thickness of nanoflakes is about 10-40 nm. A possible formation mechanism for Ni flower-like architectures was proposed and it was confirmed by the control experiments. The Ni architectures exhibited a saturation magnetization (M{sub s}) of 47.7 emu/g and a large coercivity (H{sub cj}) of 332.3 Oe. The epoxy resin compositesmore » with 20 vol% Ni sample provided good electromagnetic wave absorption performance (reflection loss <-20 dB) in the range of 2.8-6.3 GHz over absorber thickness of 2.6-5.0 mm. - Graphical abstract: Monodispersed Ni flower-like architectures composed of nanoflakes were synthesized through a facile solvent-thermal process. The Ni architectures exhibited a large coercivity and enhanced electromagnetic wave absorption in GHz. Highlights: > Flower-like architectures composed of nanoflakes. > A possible formation mechanism for Ni flower-like architectures was proposed. > Sodium alkali, PEG, and NaCl played the important roles in the final morphology. > Ni architectures exhibited a large coercivity (H{sub cj}) of 332.3 Oe. > Efficient electromagnetic absorption (RL<-20 dB) was provided in 2.8-6.3 GHz.« less

Generation of ordinary mode electromagnetic radiation near the upper hybrid frequency in the magnetosphere

NASA Technical Reports Server (NTRS)

Ashour-Abdalla, M.; Okuda, H.

1984-01-01

It is shown by means of plasma numerical simulations that long-wavelength ordinary mode electromagnetic radiation can be generated from short-wavelength electrostatic waves near the upper hybrid resonance frequency in an inhomogeneous plasma. A possible relation of this process to nonthermal continuum radiation in the magnetosphere is discussed.

[Low-energy wideband electromagnetic radiation and manual therapy in the treatment of neurological manifestations of spinal osteochondrosis].

PubMed

Afoshin, S A; Gerasimenko, M Iu

2006-01-01

It is shown that the advanced technique of low-energy wideband electromagnetic radiation improves vascular tonicity and peripheral circulation while a modified technique of manual therapy facilitates movements in the affected part of the spine and reduces tonicity of the muscles involved in the pathological process.

Facile synthesis of magnetic biochar/Fe3O4 nanocomposites using electro-magnetization technique and its application on the removal of acid orange 7 from aqueous media.

PubMed

Jung, Kyung-Won; Choi, Brian Hyun; Jeong, Tae-Un; Ahn, Kyu-Hong

2016-11-01

This study introduces a new methodology to synthesize magnetic biochar/Fe3O4 nanocomposites (M-BC) from marine macroalgae using a facile electro-magnetization technique. M-BC was prepared by stainless steel electrode-based electrochemical system, followed by pyrolysis. Physical and chemical analyses revealed that the porosity and magnetic properties were simultaneously improved via the electro-magnetization process, which enabled not only higher adsorption performance, but also easier separation/recovery from aqueous media at post-adsorption stage using a bar magnet. The adsorption equilibrium studies reveal that the Sips model satisfactorily predicts the adsorption capacity, which found to be 190, 297, and 382mgg(-1) at 10, 20, and 30°C, respectively. The overall findings indicate that one-step electro-magnetization technique can be effectively utilized for the fabrication of biochar with concurrent acquisition of porosity and magnetism, which can bring about new directions in the practical use of adsorption process in environment remediation and mitigate crises originating from it. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fabrication process and electromagnetic wave absorption characterization of a CNT/Ni/epoxy nanocomposite.

PubMed

Ryu, Seongwoo; Mo, Chan Bin; Lee, Haeshin; Hong, Soon Hyung

2013-11-01

Since carbon nanotube (CNT) was first discovered in 1991, it has been considered as a viable type of conductive filler for electromagnetic wave absorption materials in the GHz range. In this paper, pearl-necklace-structure CNT/Ni nano-powders were fabricated by a polyol process as conductive fillers. Compared to synthesized CNT, pearl-necklace Ni-decorated CNT increased the electrical conductivity by an order of 1 due to the enhancement of the Ni-conductive network. Moreover, the decorated Ni particles prevented the agglomeration of CNTs by counterbalancing the Van der Walls interaction between the CNTs. A CNT/Ni nanocomposite showed a homogeneous dispersion in an epoxy-based matrix. This enhanced physical morphology and electrical properties lead to an increase in the loss tangent and reflection loss in the CNT/Ni/Epoxy nanocomposite compared to these characteristics of a CNT/Epoxy nanocomposite in range of 8-12 GHz. The electromagnetic wave absorption properties of CNT/Ni/epoxy nanocomposites will provide enormous opportunities for electronic applications where lightweight EMI shielding or electro-magnetic wave absorption properties are necessary.

Global simulation of the induction heating TSSG process of SiC for the effects of Marangoni convection, free surface deformation and seed rotation

NASA Astrophysics Data System (ADS)

Yamamoto, Takuya; Okano, Yasunori; Ujihara, Toru; Dost, Sadik

2017-07-01

A global numerical simulation was performed for the induction heating Top-Seeded Solution Growth (TSSG) process of SiC. Analysis included the furnace and growth melt. The effects of interfacial force due to free surface tension gradient, the RF coil-induced electromagnetic body force, buoyancy, melt free surface deformation, and seed rotation were examined. The simulation results showed that the contributions of free surface tension gradient and the electromagnetic body force to the melt flow are significant. Marangoni convection affects the growth process adversely by making the melt flow downward in the region under the seed crystal. This downward flow reduces carbon flux into the seed and consequently lowers growth rate. The effects of free surface deformation and seed rotation, although positive, are not so significant compared with those of free surface tension gradient and the electromagnetic body force. Due to the small size of the melt the contribution of buoyancy is also small.

Electromagnetic Biostimulation of Living Cultures for Biotechnology, Biofuel and Bioenergy Applications

PubMed Central

Hunt, Ryan W.; Zavalin, Andrey; Bhatnagar, Ashish; Chinnasamy, Senthil; Das, Keshav C.

2009-01-01

The surge of interest in bioenergy has been marked with increasing efforts in research and development to identify new sources of biomass and to incorporate cutting-edge biotechnology to improve efficiency and increase yields. It is evident that various microorganisms will play an integral role in the development of this newly emerging industry, such as yeast for ethanol and Escherichia coli for fine chemical fermentation. However, it appears that microalgae have become the most promising prospect for biomass production due to their ability to grow fast, produce large quantities of lipids, carbohydrates and proteins, thrive in poor quality waters, sequester and recycle carbon dioxide from industrial flue gases and remove pollutants from industrial, agricultural and municipal wastewaters. In an attempt to better understand and manipulate microorganisms for optimum production capacity, many researchers have investigated alternative methods for stimulating their growth and metabolic behavior. One such novel approach is the use of electromagnetic fields for the stimulation of growth and metabolic cascades and controlling biochemical pathways. An effort has been made in this review to consolidate the information on the current status of biostimulation research to enhance microbial growth and metabolism using electromagnetic fields. It summarizes information on the biostimulatory effects on growth and other biological processes to obtain insight regarding factors and dosages that lead to the stimulation and also what kind of processes have been reportedly affected. Diverse mechanistic theories and explanations for biological effects of electromagnetic fields on intra and extracellular environment have been discussed. The foundations of biophysical interactions such as bioelectromagnetic and biophotonic communication and organization within living systems are expounded with special consideration for spatiotemporal aspects of electromagnetic topology, leading to the potential of multipolar electromagnetic systems. The future direction for the use of biostimulation using bioelectromagnetic, biophotonic and electrochemical methods have been proposed for biotechnology industries in general with emphasis on an holistic biofuel system encompassing production of algal biomass, its processing and conversion to biofuel. PMID:20057958

Detection and characterization of lightning-based sources using continuous wavelet transform: application to audio-magnetotellurics

NASA Astrophysics Data System (ADS)

Larnier, H.; Sailhac, P.; Chambodut, A.

2018-01-01

Atmospheric electromagnetic waves created by global lightning activity contain information about electrical processes of the inner and the outer Earth. Large signal-to-noise ratio events are particularly interesting because they convey information about electromagnetic properties along their path. We introduce a new methodology to automatically detect and characterize lightning-based waves using a time-frequency decomposition obtained through the application of continuous wavelet transform. We focus specifically on three types of sources, namely, atmospherics, slow tails and whistlers, that cover the frequency range 10 Hz to 10 kHz. Each wave has distinguishable characteristics in the time-frequency domain due to source shape and dispersion processes. Our methodology allows automatic detection of each type of event in the time-frequency decomposition thanks to their specific signature. Horizontal polarization attributes are also recovered in the time-frequency domain. This procedure is first applied to synthetic extremely low frequency time-series with different signal-to-noise ratios to test for robustness. We then apply it on real data: three stations of audio-magnetotelluric data acquired in Guadeloupe, oversea French territories. Most of analysed atmospherics and slow tails display linear polarization, whereas analysed whistlers are elliptically polarized. The diversity of lightning activity is finally analysed in an audio-magnetotelluric data processing framework, as used in subsurface prospecting, through estimation of the impedance response functions. We show that audio-magnetotelluric processing results depend mainly on the frequency content of electromagnetic waves observed in processed time-series, with an emphasis on the difference between morning and afternoon acquisition. Our new methodology based on the time-frequency signature of lightning-induced electromagnetic waves allows automatic detection and characterization of events in audio-magnetotelluric time-series, providing the means to assess quality of response functions obtained through processing.

[The specific features of the development of metabolic and regenerative processes under the action of low-intensity electromagnetic radiation in radiation exposure conditions (an experimental study)].

PubMed

Korolev, Yu N; Mihajlik, L V; Nikulina, L A; Geniatulina, M S

The experiments on male white rats with the use of biochemical, photo-optical, and electron-microscopic techniques have demonstrated that the use of low-intensity electromagnetic radiation of ultrahigh frequency (EMR UHF) and low-intensity low-frequency magnetic field (MF) during the post-irradiation period (within 21 days after exposure to radiation) enhanced the metabolic and regenerative processes in the testes and liver. It was shown that the application of MF largely intensified the antioxidant activity whereas EMR UHF preferentially stimulated the biosynthetic processes as well as the processes of cellular and intracellular regeneration.

An analysis of how electromagnetic induction and Faraday's law are presented in general physics textbooks, focusing on learning difficulties

NASA Astrophysics Data System (ADS)

Guisasola, Jenaro; Zuza, Kristina; Almudi, José-Manuel

2013-07-01

Textbooks are a very important tool in the teaching-learning process and influence important aspects of the process. This paper presents an analysis of the chapter on electromagnetic induction and Faraday's law in 19 textbooks on general physics for first-year university courses for scientists and engineers. This analysis was based on criteria formulated from the theoretical framework of electromagnetic induction in classical physics and students' learning difficulties concerning these concepts. The aim of the work presented here is not to compare a textbook against the ideal book, but rather to try and find a series of explanations, examples, questions, etc that provide evidence on how the topic is presented in relation to the criteria above. It concludes that despite many aspects being covered properly, there are others that deserve greater attention.

Low-loss electromagnetic composites for RF and microwave applications.

PubMed

Wang, Hong; Yang, Haibo; Xiang, Feng; Yao, Xi

2011-09-01

Low-loss electromagnetic composites with high permittivity and permeability will benefit the miniaturization and multifunctional of RF devices. A kind of low-loss dielectric-magnetic ceramic-ceramic composite was developed by hybrid processing technology with the goal of integrating the dielectric properties and magnetic properties. The hybrid processing technology exhibits the advantage of lowered sintering temperatures for the composites while retaining good microstructure and high performance. By introducing elastomer as matrix, a kind of flexible low-loss dielectric-magnetic ceramic-polymer composite was prepared and studied. The obtained flexible dielectric-magnetic ceramic-polymer composite exhibited low loss and good mechanical properties. The results show good effects on lowering the dielectric loss and extending the cut-off magnetic frequency of the electromagnetic composite. Methods for tailoring the properties of the multifunctional composites were proposed and discussed.

Nucleotide and bivalent cation specificity of the insulin-granule proton translocase.

PubMed Central

Hutton, J C; Peshavaria, M

1983-01-01

1. The nucleotide and bivalent cation specificity of the proton translocase activity of insulin secretory granules was investigated by assessing the inhibitor-sensitive rates of nucleotide hydrolysis by these organelles in relation to their chemiosmotic properties. 2. The relative rates of nucleotide hydrolysis by freeze/thawed granule preparations were: Mg2+ATP (100%) greater than Mg2+GTP (55%) greater than Mg2+UTP (48%) greater than Mg2+ITP (44%) greater than Mg2+CTP (23%) greater than Mg2+TTP (20%), and by intact granules were: Mg2+ATP (100%) greater than Mg2+ITP (74%) greater than Mg2+GTP (60%) greater than Mg2+CTP (35%). Mg2+ATP, Mg2+GTP and Mg2+ITP hydrolyses were inhibited by tributyltin and stimulated, in intact granules, by the protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone; Mg2+CTP hydrolysis was not markedly affected by these compounds. Correspondingly, only Mg2+ATP, Mg2+GTP and Mg2+ITP produced large changes in the delta psi and delta mu H+ across the granule membrane. 3. The relative rates of maximal ATPase activity stimulated by bivalent cations in freeze/thawed granule preparations were: Mg2+ (100%) greater than Mn2+ (82%) greater than Ca2+ (40%) greater than Co2+ (36%) greater than Zn2+ (0%), and in intact granules were: Mg2+ (100%) greater than Mn2+ (85%) greater than Co2+ (61%) greater than Ca2+ (42%). Tributyltin and carbonyl cyanide p-trifluoromethoxyphenylhydrazone affected Mg2+-, Mn2+- and Co2+-activated, but not Ca2+-activated, ATP hydrolysis. Correspondingly, only Mg2+, Mn2+ and Co2+ supported the generation of a delta psi and delta mu H+ across granule membranes in the presence of ATP. 4. The results were consistent with a single proton translocase that had its catalytic site exposed on the external face of the granule membrane. The indicated specificity (Mg2+ATP = Mn2+ATP greater than Co2+ATP greater than Mg2+GTP greater than Mg2+ITP) was similar to that of enzymes described in membrane fractions prepared from adenohypophyseal tissue, adrenal chromaffin granules and yeast vacuoles. The insulin-granule activity thus appears to be a type of proton translocase, which is characteristic of intracellular storage vesicles in eukaryotic cells. PMID:6303313

ATHENA X-IFU 300 K-50 mK cryochain demonstrator cryostat

NASA Astrophysics Data System (ADS)

Prouvé, T.; Duval, J. M.; Charles, I.; Yamasaki, N. Y.; Mitsuda, K.; Nakagawa, T.; Shinozaki, K.; Tokoku, C.; Yamamoto, R.; Minami, Y.; Le Du, M.; Andre, J.; Daniel, C.; Linder, M.

2018-01-01

In the framework of the ESA X-ray mission ATHENA, scheduled for launch in 2028, an ESA Core Technology Program (CTP) was started in 2016 to build a flight like cryostat demonstrator in parallel with the phase A studies of the ATHENA/X-IFU instrument [1,2]. As part of this CTP, called the Detector Cooling System (DCS), design, manufacturing and test of a cryostat including existing space coolers will be done. In addition to the validation of thermal performance, a Focal Plan Assembly (FPA) demonstrator using Transition Edge Sensors (TES) detector technology will be also integrated and its performance characterized versus the environment provided by the cryostat. This is a unique opportunity to validate many crucial issues of the cryogenic part of such a sensitive instrument. A dedicated activity within this CTP-DCS is the demonstration of the 300 K-50 mK cooling chain in a Ground System Equipment (GSE) cryostat. The studies are focused on the operation of the space coolers, which is made possible by the use of a ground cooler for cooling cryogenic shields and mechanical supports. Thanks to the modularity of the cryostat, several cooling chains could be tested. In the base line configuration described here, the low temperature stage is the CEA hybrid sorption/ADR 50 mK cooler with thermal interfaces at 4 K and 2 K. 4 K cooling is accomplished by a 4 K Joule-Thomson (JT) cryocooler and its Stirling precooler provided by JAXA. Regarding the 2 K stage, at first a 2 K JT from JAXA will be used. Alternatively, a 2 K JT cooler from RAL could replace the JAXA 2 K JT. In both cases new prototype(s) of a 2 K JT will be implemented, precooled by the EM 15 K pule tube cooler from Air Liquide. This test program is also the opportunity to validate the operation of the cryochain with respect to various requirements, such as time constant and temperature stabilities. This would bring us valuable inputs to integrate the cryochain in DCS cryostat or for the X-IFU phase A studies. This cryochain demonstration is also a critical milestone for the SPICA mission [3]. The design of the cryostat and first thermal validations both before and after integration of the JAXA JT coolers are presented in this paper.

A triangular prism solid and shell interactive mapping element for electromagnetic sheet metal forming process

NASA Astrophysics Data System (ADS)

Cui, Xiangyang; Li, She; Feng, Hui; Li, Guangyao

2017-05-01

In this paper, a novel triangular prism solid and shell interactive mapping element is proposed to solve the coupled magnetic-mechanical formulation in electromagnetic sheet metal forming process. A linear six-node "Triprism" element is firstly proposed for transient eddy current analysis in electromagnetic field. In present "Triprism" element, shape functions are given explicitly, and a cell-wise gradient smoothing operation is used to obtain the gradient matrices without evaluating derivatives of shape functions. In mechanical field analysis, a shear locking free triangular shell element is employed in internal force computation, and a data mapping method is developed to transfer the Lorentz force on solid into the external forces suffered by shell structure for dynamic elasto-plasticity deformation analysis. Based on the deformed triangular shell structure, a "Triprism" element generation rule is established for updated electromagnetic analysis, which means inter-transformation of meshes between the coupled fields can be performed automatically. In addition, the dynamic moving mesh is adopted for air mesh updating based on the deformation of sheet metal. A benchmark problem is carried out for confirming the accuracy of the proposed "Triprism" element in predicting flux density in electromagnetic field. Solutions of several EMF problems obtained by present work are compared with experiment results and those of traditional method, which are showing excellent performances of present interactive mapping element.

Design and Fabrication of Helmholtz Coils to Study the Effects of Pulsed Electromagnetic Fields on the Healing Process in Periodontitis: Preliminary Animal Results

PubMed Central

Haghnegahdar, A; Khosrovpanah, H; Andisheh-Tadbir, A; Mortazavi, Gh; Saeedi Moghadam, M; Mortazavi, SMJ; Zamani, A; Haghani, M; Shojaei Fard, M; Parsaei, H; Koohi, O

2014-01-01

Background: Effects of electromagnetic fields on healing have been investigated for centuries. Substantial data indicate that exposure to electromagnetic field can lead to enhanced healing in both soft and hard tissues. Helmholtz coils are devices that generate pulsed electromagnetic fields (PEMF). Objective: In this work, a pair of Helmholtz coils for enhancing the healing process in periodontitis was designed and fabricated. Method: An identical pair of square Helmholtz coils generated the 50 Hz magnetic field.  This device was made up of two parallel coaxial circular coils (100 turns in each loop, wound in series) which were separated from each other by a distance equal to the radius of one coil (12.5 cm). The windings of our Helmholtz coil was made of standard 0.95mm wire to provide the maximum possible current. The coil was powered by a function generator.  Results: The Helmholtz Coils generated a uniform magnetic field between its coils. The magnetic field strength at the center of the space between two coils was 97.6 μT. Preliminary biological studies performed on rats show that exposure of laboratory animals to pulsed electromagnetic fields enhanced the healing of periodontitis. Conclusion: Exposure to PEMFs can lead to stimulatory physiological effects on cells and tissues such as enhanced healing of periodontitis. PMID:25505775

Electromagnetic Waves with Frequencies Near the Local Proton Gryofrequency: ISEF-3 1 AU Observations

NASA Technical Reports Server (NTRS)

Tsurutani, B.

1993-01-01

Low Frequency electromagnetic waves with periods near the local proton gyrofrequency have been detected near 1 AU by the magnetometer onboard ISEE-3. For these 1 AU waves two physical processes are possible: solar wind pickup of nuetral (interstellar?) particles and generation by relativistic electron beams propagating from the Sun.

Structure and electromagnetic properties of FeSiAl particles coated by MgO

NASA Astrophysics Data System (ADS)

Zhang, Yu; Zhou, Ting-dong

2017-03-01

FeSiAl particles with a layer of MgO surface coating have excellent soft magnetic and electromagnetic properties. In order to obtain the FeSiAl/MgO composites, Mg(OH)2 sol prepared by sol-gel process was well-mixed with FeSiAl flake particles, and then treated by calcination at 823 K in vacuum. The microstructural, morphological and electromagnetic parameters of FeSiAl/MgO particles were tested. Accordingly, the electromagnetic wave reflection loss in the frequency range of 0.5-18 GHz was calculated. The results show that the surface coating increases coercivity Hc and decreases complex permittivity, leading to a good impedance matching. When the coating amount was 7.5%, reflection loss of the composite particles can reach to -33 dB.

Towards an electro-magnetic field separation of deposited material implemented in an ion beam sputter process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malobabic, Sina; Jupe, Marco; Ristau, Detlev

Nowadays, Ion Beam Sputter (IBS) processes are very well optimized on an empirical basis. To achieve further progresses, a modification of the IBS process by guiding the coating material using an axial magnetic field and an additional electrical field has been studied. The electro-magnetic (EM) field leads to a significant change in plasma properties and deposition rate distributions, whereas an increase in deposition rate along the centerline of the axial EM field around 150% was observed. These fundamental studies on the prototype are the basis for the development of an applicable and workable design of a separation device.

Nonlinear mechanism for the generation of electromagnetic fields in a magnetized plasma by the beatings of waves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aburjania, G. D.; Machabeli, G. Z.; Kharshiladze, O. A.

2006-07-15

The modulational instability in a plasma in a strong constant external magnetic field is considered. The plasmon condensate is modulated not by conventional low-frequency ion sound but by the beatings of two high-frequency transverse electromagnetic waves propagating along the magnetic field. The instability reduces the spatial scales of Langmuir turbulence along the external magnetic field and generates electromagnetic fields. It is shown that, for a pump wave with a sufficiently large amplitude, the effect described in the present paper can be a dominant nonlinear process.

Warrior Transition Leader: Medical Rehabilitation Handbook

DTIC Science & Technology

2011-01-01

serve. rE f E r E n c E S 1. http://www.army.mil/warriorcarenews/. Accessed January 24, 2011. 2. Warrior Transition Command Web site. http...www.wtc.army.mil/about_us/ ctp.html. Accessed January 24, 2011. 3. Leipold JD. Warrior Transition Command stands up at Pentagon. US Army Web site. Army...January 24, 2011. 4. Warrior Transition Command Web site. http://wtc.armylive.dodlive.mil/ about-wtu/. Accessed January 24, 2011. 5. Leipold JD

Replication of a carcinogenic nitropyrene DNA lesion by human Y-family DNA polymerase

PubMed Central

Kirouac, Kevin N.; Basu, Ashis K.; Ling, Hong

2013-01-01

Nitrated polycyclic aromatic hydrocarbons are common environmental pollutants, of which many are mutagenic and carcinogenic. 1-Nitropyrene is the most abundant nitrated polycyclic aromatic hydrocarbon, which causes DNA damage and is carcinogenic in experimental animals. Error-prone translesion synthesis of 1-nitropyrene–derived DNA lesions generates mutations that likely play a role in the etiology of cancer. Here, we report two crystal structures of the human Y-family DNA polymerase iota complexed with the major 1-nitropyrene DNA lesion at the insertion stage, incorporating either dCTP or dATP nucleotide opposite the lesion. Polι maintains the adduct in its active site in two distinct conformations. dCTP forms a Watson–Crick base pair with the adducted guanine and excludes the pyrene ring from the helical DNA, which inhibits replication beyond the lesion. By contrast, the mismatched dATP stacks above the pyrene ring that is intercalated in the helix and achieves a productive conformation for misincorporation. The intra-helical bulky pyrene mimics a base pair in the active site and facilitates adenine misincorporation. By structure-based mutagenesis, we show that the restrictive active site of human polη prevents the intra-helical conformation and A-base misinsertions. This work provides one of the molecular mechanisms for G to T transversions, a signature mutation in human lung cancer. PMID:23268450

Infliximab Biosimilar (CT-P13; Infliximab-dyyb): A Review in Autoimmune Inflammatory Diseases.

PubMed

Blair, Hannah A; Deeks, Emma D

2016-10-01

Infliximab biosimilar (CT-P13/infliximab-dyyb; Remsima ® , Inflectra ® ) is approved in several countries for use in all indications for which reference infliximab (Remicade ® ) is approved, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis, psoriasis, Crohn's disease, and ulcerative colitis. Clinical data contributing to the EU approval of infliximab biosimilar were obtained from two pivotal double-blind clinical trials in patients with AS (PLANETAS) or RA (PLANETRA). Infliximab biosimilar demonstrated equivalence to reference infliximab in terms of its pharmacokinetic profile in patients with AS, patients with RA, and in healthy volunteers, and in terms of its efficacy in patients with RA. Clinical response rates in patients with RA or AS were maintained over the longer term (up to 102 weeks). In addition, the efficacy of infliximab biosimilar in patients with RA or Crohn's disease and ulcerative colitis [i.e. inflammatory bowel disease (IBD)] has been demonstrated in the real-world setting. Infliximab biosimilar was generally well tolerated, with a tolerability profile similar to that of reference infliximab. Switching from reference infliximab to infliximab biosimilar had no detrimental effect on efficacy, safety, or immunogenicity compared with continuous infliximab biosimilar therapy, according to the extensions of PLANETAS and PLANETRA, and real-world data in IBD. Current evidence therefore suggests that infliximab biosimilar is a useful alternative to reference infliximab in patients with autoimmune inflammatory diseases.

CyDNA: Synthesis and Replication of Highly Cy-Dye Substituted DNA by an Evolved Polymerase

PubMed Central

2010-01-01

DNA not only transmits genetic information but can also serve as a versatile supramolecular scaffold. Here we describe a strategy for the synthesis and replication of DNA displaying hundreds of substituents using directed evolution of polymerase function by short-patch compartmentalized self-replication (spCSR) and the widely used fluorescent dye labeled deoxinucleotide triphosphates Cy3-dCTP and Cy5-dCTP as substrates. In just two rounds of spCSR selection, we have isolated a polymerase that allows the PCR amplification of double stranded DNA fragments up to 1kb, in which all dC bases are substituted by its fluorescent dye-labeled equivalent Cy3- or Cy5-dC. The resulting “CyDNA” displays hundreds of aromatic heterocycles on the outside of the DNA helix and is brightly colored and highly fluorescent. CyDNA also exhibits significantly altered physicochemical properties compared to standard B-form DNA, including loss of silica and intercalating dye binding, resistance to cleavage by some endonucleases, an up to 40% increased apparent diameter as judged by atomic force microscopy and organic phase partitioning during phenol extraction. CyDNA also displays very bright fluorescence enabling significant signal gains in microarray and microfluidic applications. CyDNA represents a step toward a long-term goal of the encoded synthesis of DNA-based polymers of programmable and evolvable sequence and properties. PMID:20235594

Epileptic negative drop attacks in atypical benign partial epilepsy: a neurophysiological study.

PubMed

Hirano, Yoshiko; Oguni, Hirokazu; Osawa, Makiko

2009-03-01

We conducted a computer-assisted polygraphic analysis of drop attacks in a child with atypical benign partial epilepsy (ABPE) to investigate neurophysiological characteristics. The patient was a six-year two-month-old girl, who had started to have focal motor seizures, later combined with daily epileptic negative myoclonus (ENM) and drop attacks, causing multiple injuries. We studied episodes of ENM and drop attacks using video-polygraphic and computer-assisted back-averaging analysis. A total of 12 ENM episodes, seven involving the left arm (ENMlt) and five involving both arms (ENMbil), and five drop attacks were captured for analysis. All episodes were time-locked to spike-and-wave complexes (SWC) arising from both centro-temporo-parietal (CTP) areas. The latency between the onset of SWC and ENMlt, ENMbil, and drop attacks reached 68 ms, 42 ms, and 8 ms, respectively. The height of the spike as well as the slow-wave component of SWC for drop attacks were significantly larger than that for both ENMlt and ENMbil (p < 0.05). Drop attacks were considered to be epileptic negative myoclonus involving not only upper proximal but also axial muscles, causing the body to fall. Thus, drop attacks in ABPE are considered to be epileptic negative drop attacks arising from bilateral CTP foci and differ from drop attacks of a generalized origin seen in Lennox-Gastaut syndrome and myoclonic-astatic epilepsy.

Cost-effectiveness analysis of ibrutinib in patients with Waldenström macroglobulinemia in Italy.

PubMed

Aiello, Andrea; D'Ausilio, Anna; Lo Muto, Roberta; Randon, Francesca; Laurenti, Luca

2017-01-01

Background and Objective: Ibrutinib has recently been approved in Europe for Waldenström Macroglobulinemia (WM) in symptomatic patients who have received at least one prior therapy, or in first-line treatment for patients unsuitable for chemo-immunotherapy. The aim of the study is to estimate the incremental cost-effectiveness ratio (ICER) of ibrutinib in relapse/refractory WM, compared with the Italian current therapeutic pathways (CTP). Methods: A Markov model was adapted for Italy considering the National Health System perspective. Input data from literature as well as global trials were used. The percentage use of therapies, and healthcare resources consumption were estimated according to expert panel advice. Drugs ex-factory prices and national tariffs were used for estimating costs. The model had a 15-year time horizon, with a 3.0% discount rate for both clinical and economic data. Deterministic and probabilistic sensitivity analyses were performed to test the results strength. Results: Ibrutinib resulted in increased Life Years Gained (LYGs) and increased costs compared to CTP, with an ICER of €52,698/LYG. Sensitivity analyses confirmed the results of the BaseCase. Specifically, in the probabilistic analysis, at a willingness to pay threshold of €60,000/LYG ibrutinib was cost-effective in 84% of simulations. Conclusions: Ibrutinib has demonstrated a positive cost-effectiveness profile in Italy.