Mechanism for CCC DNA synthesis in hepadnaviruses.

PubMed

Sohn, Ji A; Litwin, Samuel; Seeger, Christoph

2009-11-30

Hepadnavirus replication requires the synthesis of a covalently closed circular (CCC) DNA from the relaxed circular (RC) viral genome by an unknown mechanism. CCC DNA formation could require enzymatic activities of the viral reverse transcriptase (RT), or cellular DNA repair enzymes, or both. Physical mapping of the 5' and 3' ends of RC DNA and sequence analysis of CCC DNA revealed that CCC DNA synthesis requires the removal of the RT and an RNA oligomer from the 5' ends of minus and plus strand DNA, respectively, removal of sequences from the terminally redundant minus strand, completion of the less than full-length plus strand, and ligation of the ends. Two models have been proposed that could explain CCC DNA formation. The first (model 1) invokes a role for the RT to catalyze a cleavage-ligation reaction leading to the formation of a unit length minus strand in CCC DNA and a DNA repair reaction for the completion and ligation of plus strand DNA; the second (model 2) predicts that CCC DNA formation depends entirely on cellular DNA repair enzymes. To determine which mechanism is utilized, we developed cell lines expressing duck hepatitis B virus genomes carrying mutations permitting us to follow the fate of viral DNA sequences during their conversion from RC to CCC DNA. Our results demonstrated that the oligomer at the 5' end of minus strand DNA is completely or at least partially removed prior to CCC DNA synthesis. The results indicated that both RC DNA strands undergo DNA repair reactions carried out by the cellular DNA repair machinery as predicted by model 2. Thus, our study provided the basis for the identification of the cellular components required for CCC DNA formation.

PRMT5 restricts hepatitis B virus replication through epigenetic repression of covalently closed circular DNA transcription and interference with pregenomic RNA encapsidation.

PubMed

Zhang, Wen; Chen, Jieliang; Wu, Min; Zhang, Xiaonan; Zhang, Min; Yue, Lei; Li, Yaming; Liu, Jiangxia; Li, Baocun; Shen, Fang; Wang, Yang; Bai, Lu; Protzer, Ulrike; Levrero, Massimo; Yuan, Zhenghong

2017-08-01

Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. The covalently closed circular DNA (cccDNA) minichromosome, which serves as the template for the transcription of viral RNAs, plays a key role in viral persistence. While accumulating evidence suggests that cccDNA transcription is regulated by epigenetic machinery, particularly the acetylation of cccDNA-bound histone 3 (H3) and H4, the potential contributions of histone methylation and related host factors remain obscure. Here, by screening a series of methyltransferases and demethylases, we identified protein arginine methyltransferase 5 (PRMT5) as an effective restrictor of HBV transcription and replication. In cell culture-based models for HBV infection and in liver tissues of patients with chronic HBV infection, we found that symmetric dimethylation of arginine 3 on H4 on cccDNA was a repressive marker of cccDNA transcription and was regulated by PRMT5 depending on its methyltransferase domain. Moreover, PRMT5-triggered symmetric dimethylation of arginine 3 on H4 on the cccDNA minichromosome involved an interaction with the HBV core protein and the Brg1-based human SWI/SNF chromatin remodeler, which resulted in down-regulation of the binding of RNA polymerase II to cccDNA. In addition to the inhibitory effect on cccDNA transcription, PRMT5 inhibited HBV core particle DNA production independently of its methyltransferase activity. Further study revealed that PRMT5 interfered with pregenomic RNA encapsidation by preventing its interaction with viral polymerase protein through binding to the reverse transcriptase-ribonuclease H region of polymerase, which is crucial for the polymerase-pregenomic RNA interaction. PRMT5 restricts HBV replication through a two-part mechanism including epigenetic suppression of cccDNA transcription and interference with pregenomic RNA encapsidation; these findings improve the understanding of epigenetic regulation of HBV transcription and host-HBV interaction, thus providing new insights into targeted therapeutic intervention. (Hepatology 2017;66:398-415). © 2017 by the American Association for the Study of Liver Diseases.

[A quantitative real time polymerase chain reaction for detection of HBV covalently closed circular DNA in livers of the HBV infected patients].

PubMed

Wang, Mei-Rong; Qiu, Ning; Lu, Shi-Chun; Xiu, Dian-Rong; Yu, Jian-Guo; Li, Tong; Liu, Xue-En; Zhuang, Hui

2011-05-01

To establish and optimize a sensitive and specific quantitative real-time polymerase chain reaction (PCR) method for detection of hepatitis B virus covalently closed circular DNA (HBV cccDNA) in liver tissue. Specific primers and probes were designed to detect HBV DNA (tDNA) and cccDNA. A series of plasmids (3.44 × 10(0) - 3.44 × 10(9) copies/µl) containing a full double-stranded copies of HBV genome (genotype C) were used to establish the standard curve of real-time PCR. Liver samples of 33 patients with HBV related hepatocellular carcinoma (HCC), 13 Chronic hepatitis B patients (CHB) and 10 non-HBV patients were collected to verify the sensitivity and specificity of the assay. A fraction of extracted DNA was digested with a Plasmid-Safe ATP-dependent Dnase (PSAD) for HBV cccDNA detection and the remaining was used for tDNA and β-globin detection. The amount (copies/cell) of HBV cccDNA and tDNA were measured by a real-time PCR, using β-globin housekeeping gene as a quantitation standard. The standard curves of real-time PCR with a linear range of 3.44 × 10(0) to 3.44 × 10(9) copies/µl were established for detecting HBV cccDNA and tDNA, and both of the lowest detection limits of HBV cccDNA and tDNA were 3.44 × 10(0) copies/µl. The lowest quantitation levels of HBV cccDNA in liver tissues tested in 33 HBV related HCC patients and 13 CHB patients were 0.003 copies/cell and 0.031 copies/cell, respectively. HBV cccDNA and tDNA in liver tissue of 10 non-HBV patient appeared to be negative. The true positive rate was increasing through the digestion of HBV DNA by PSAD, and the analytic specificity of cccDNA detection improved by 7.24 × 10(2) times. Liver tissues of 2 patients were retested 5 times in the PCR for detecting cccDNA and the coefficient of variations on cycle threshold (Ct) were between 0.224% - 0.609%. A highly sensitive and specific quantitative real time PCR method for the detection of HBV cccDNA in liver tissue was established and could be used for clinical and epidemiological studies.

Does Tyrosyl DNA Phosphodiesterase-2 Play a Role in Hepatitis B Virus Genome Repair?

PubMed Central

Boregowda, Rajeev; Sohn, Ji A.; Ledesma, Felipe Cortes; Caldecott, Keith W.; Seeger, Christoph; Hu, Jianming

2015-01-01

Hepatitis B virus (HBV) replication and persistence are sustained by a nuclear episome, the covalently closed circular (CCC) DNA, which serves as the transcriptional template for all viral RNAs. CCC DNA is converted from a relaxed circular (RC) DNA in the virion early during infection as well as from RC DNA in intracellular progeny nucleocapsids via an intracellular amplification pathway. Current antiviral therapies suppress viral replication but cannot eliminate CCC DNA. Thus, persistence of CCC DNA remains an obstacle toward curing chronic HBV infection. Unfortunately, very little is known about how CCC DNA is formed. CCC DNA formation requires removal of the virally encoded reverse transcriptase (RT) protein from the 5’ end of the minus strand of RC DNA. Tyrosyl DNA phosphodiesterase-2 (Tdp2) was recently identified as the enzyme responsible for cleavage of tyrosyl-5’ DNA linkages formed between topoisomerase II and cellular DNA. Because the RT-DNA linkage is also a 5’ DNA-phosphotyrosyl bond, it has been hypothesized that Tdp2 might be one of several elusive host factors required for CCC DNA formation. Therefore, we examined the role of Tdp2 in RC DNA deproteination and CCC DNA formation. We demonstrated Tdp2 can cleave the tyrosyl-minus strand DNA linkage using authentic HBV RC DNA isolated from nucleocapsids and using RT covalently linked to short minus strand DNA produced in vitro. On the other hand, our results showed that Tdp2 gene knockout did not block CCC DNA formation during HBV infection of permissive human hepatoma cells and did not prevent intracellular amplification of duck hepatitis B virus CCC DNA. These results indicate that although Tdp2 can remove the RT covalently linked to the 5’ end of the HBV minus strand DNA in vitro, this protein might not be required for CCC DNA formation in vivo. PMID:26079492

Interplay between SIRT1 and hepatitis B virus X protein in the activation of viral transcription.

PubMed

Deng, Jian-Jun; Kong, Ka-Yiu Edwin; Gao, Wei-Wei; Tang, Hei-Man Vincent; Chaudhary, Vidyanath; Cheng, Yun; Zhou, Jie; Chan, Chi-Ping; Wong, Danny Ka-Ho; Yuen, Man-Fung; Jin, Dong-Yan

2017-04-01

Hepatitis B virus (HBV) genome is organized into a minichromosome known as covalently closed circular DNA (cccDNA), which serves as the template for all viral transcripts. SIRT1 is an NAD + -dependent protein deacetylase which activates HBV transcription by promoting the activity of cellular transcription factors and coactivators. How SIRT1 and viral transactivator X protein (HBx) might affect each other remains to be clarified. In this study we show synergy and mutual dependence between SIRT1 and HBx in the activation of HBV transcription. All human sirtuins SIRT1 through SIRT7 activated HBV gene expression. The steady-state levels of SIRT1 protein were elevated in HBV-infected liver tissues and HBV-replicating hepatoma cells. SIRT1 interacted with HBx and potentiated HBx transcriptional activity on precore promoter and covalently closed circular DNA (cccDNA) likely through a deacetylase-independent mechanism, leading to more robust production of cccDNA, pregenomic RNA and surface antigen. SIRT1 and HBx proteins were more abundant when both were expressed. SIRT1 promoted the recruitment of HBx as well as cellular transcriptional factors and coactivators such as PGC-1α and FXRα to cccDNA. Depletion of SIRT1 suppressed HBx recruitment. On the other hand, SIRT1 recruitment to cccDNA was compromised when HBx was deficient. Whereas pharmaceutical agonists of SIRT1 such as resveratrol activated HBV transcription, small-molecule inhibitors of SIRT1 including sirtinol and Ex527 exhibited anti-HBV activity. Taken together, our findings revealed not only the interplay between SIRT1 and HBx in the activation of HBV transcription but also new strategies and compounds for developing antivirals against HBV. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of hydrolyzable tannins (punicalagin, punicalin and geraniin) as novel inhibitors of hepatitis B virus covalently closed circular DNA

PubMed Central

Liu, Chunlan; Cai, Dawei; Zhang, Lin; Tang, Wei; Yan, Ran

2017-01-01

The development of new agents to target HBV cccDNA is urgently needed because of the limitations of current available drugs for treatment of hepatitis B. By using a cell-based assay in which the production of HBeAg is in a cccDNA-dependent manner, we screened a compound library derived from Chinese herbal remedies for inhibitors against HBV cccDNA. Three hydrolyzable tannins, specifically punicalagin, punicalin and geraniin, emerged as novel anti-HBV agents. These compounds significantly reduced the production of secreted HBeAg and cccDNA in a dose-dependent manner in our assay, without dramatic alteration of viral DNA replication. Furthermore, punicalagin did not affect precore/core promoter activity, pgRNA transcription, core protein expression, or HBsAg secretion. By employing the cell-based cccDNA accumulation and stability assay, we found that these tannins significantly inhibited the establishment of cccDNA and modestly facilitated the degradation of preexisting cccDNA. Collectively, our results suggest that hydrolyzable tannins inhibit HBV cccDNA production via a dual mechanism through preventing the formation of cccDNA and promoting cccDNA decay, although the latter effect is rather minor. These hydrolyzable tannins may serve as lead compounds for the development of new agents to cure HBV infection. PMID:27591143

Identification of hydrolyzable tannins (punicalagin, punicalin and geraniin) as novel inhibitors of hepatitis B virus covalently closed circular DNA.

PubMed

Liu, Chunlan; Cai, Dawei; Zhang, Lin; Tang, Wei; Yan, Ran; Guo, Haitao; Chen, Xulin

2016-10-01

The development of new agents to target HBV cccDNA is urgently needed because of the limitations of current available drugs for treatment of hepatitis B. By using a cell-based assay in which the production of HBeAg is in a cccDNA-dependent manner, we screened a compound library derived from Chinese herbal remedies for inhibitors against HBV cccDNA. Three hydrolyzable tannins, specifically punicalagin, punicalin and geraniin, emerged as novel anti-HBV agents. These compounds significantly reduced the production of secreted HBeAg and cccDNA in a dose-dependent manner in our assay, without dramatic alteration of viral DNA replication. Furthermore, punicalagin did not affect precore/core promoter activity, pgRNA transcription, core protein expression, or HBsAg secretion. By employing the cell-based cccDNA accumulation and stability assay, we found that these tannins significantly inhibited the establishment of cccDNA and modestly facilitated the degradation of preexisting cccDNA. Collectively, our results suggest that hydrolyzable tannins inhibit HBV cccDNA production via a dual mechanism through preventing the formation of cccDNA and promoting cccDNA decay, although the latter effect is rather minor. These hydrolyzable tannins may serve as lead compounds for the development of new agents to cure HBV infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Specific functions of the Rep and Rep' proteins of porcine circovirus during copy-release and rolling-circle DNA replication

USDA-ARS?s Scientific Manuscript database

The roles of two porcine circovirus replication initiator proteins, Rep and Rep', in generating copy-release and rolling-circle DNA replication intermediates were determined. Rep uses the supercoiled closed-circular genome (ccc) to initiate leading-strand synthesis (identical to copy-release replica...

Physical Characterization of Gemini Surfactant-Based Synthetic Vectors for the Delivery of Linear Covalently Closed (LCC) DNA Ministrings

PubMed Central

Sum, Chi Hong; Nafissi, Nafiseh; Slavcev, Roderick A.; Wettig, Shawn

2015-01-01

In combination with novel linear covalently closed (LCC) DNA minivectors, referred to as DNA ministrings, a gemini surfactant-based synthetic vector for gene delivery has been shown to exhibit enhanced delivery and bioavailability while offering a heightened safety profile. Due to topological differences from conventional circular covalently closed (CCC) plasmid DNA vectors, the linear topology of LCC DNA ministrings may present differences with regards to DNA interaction and the physicochemical properties influencing DNA-surfactant interactions in the formulation of lipoplexed particles. In this study, N,N-bis(dimethylhexadecyl)-α,ω-propanediammonium(16-3-16)gemini-based synthetic vectors, incorporating either CCC plasmid or LCC DNA ministrings, were characterized and compared with respect to particle size, zeta potential, DNA encapsulation, DNase sensitivity, and in vitro transgene delivery efficacy. Through comparative analysis, differences between CCC plasmid DNA and LCC DNA ministrings led to variations in the physical properties of the resulting lipoplexes after complexation with 16-3-16 gemini surfactants. Despite the size disparities between the plasmid DNA vectors (CCC) and DNA ministrings (LCC), differences in DNA topology resulted in the generation of lipoplexes of comparable particle sizes. The capacity for ministring (LCC) derived lipoplexes to undergo complete counterion release during lipoplex formation contributed to improved DNA encapsulation, protection from DNase degradation, and in vitro transgene delivery. PMID:26561857

Alteration of Mature Nucleocapsid and Enhancement of Covalently Closed Circular DNA Formation by Hepatitis B Virus Core Mutants Defective in Complete-Virion Formation.

PubMed

Cui, Xiuji; Luckenbaugh, Laurie; Bruss, Volker; Hu, Jianming

2015-10-01

Assembly of hepatitis B virus (HBV) begins with packaging of the pregenomic RNA (pgRNA) into immature nucleocapsids (NC), which are converted to mature NCs containing the genomic relaxed circular (RC) DNA as a result of reverse transcription. Mature NCs have two alternative fates: (i) envelopment by viral envelope proteins, leading to secretion extracellularly as virions, or (ii) disassembly (uncoating) to deliver their RC DNA content into the host cell nucleus for conversion to the covalently closed circular (CCC) DNA, the template for viral transcription. How these two alternative fates are regulated remains to be better understood. The NC shell is composed of multiple copies of a single viral protein, the HBV core (HBc) protein. HBc mutations located on the surface of NC have been identified that allow NC maturation but block its envelopment. The potential effects of some of these mutations on NC uncoating and CCC DNA formation have been analyzed by transfecting HBV replication constructs into hepatoma cells. All envelopment-defective HBc mutations tested were competent for CCC DNA formation, indicating that core functions in envelopment and uncoating/nuclear delivery of RC DNA were genetically separable. Some of the envelopment-defective HBc mutations were found to alter specifically the integrity of mature, but not immature, NCs such that RC DNA became susceptible to nuclease digestion. Furthermore, CCC DNA formation could be enhanced by NC surface mutations that did or did not significantly affect mature NC integrity, indicating that the NC surface residues may be closely involved in NC uncoating and/or nuclear delivery of RC DNA. Hepatitis B virus (HBV) infection is a major health issue worldwide. HBV assembly begins with the packaging into immature nucleocapsids (NCs) of a viral RNA pregenome, which is converted to the DNA genome in mature NCs. Mature NCs are then selected for envelopment and secretion as complete-virion particles or, alternatively, can deliver their DNA to the host cell nucleus to maintain the viral genome as nuclear episomes, which are the basis for virus persistence. Previous studies have identified mutations on the capsid surface that selectively block NC envelopment without affecting NC maturation. We have now discovered that some of the same mutations result in preferential alteration of mature NCs and increased viral nuclear episomes. These findings provide important new insights into the regulation of the two alternative fates of mature NCs and suggest new ways to perturb viral persistence by manipulating levels of viral nuclear episomes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx.

PubMed

Hensel, Kai O; Cantner, Franziska; Bangert, Felix; Wirth, Stefan; Postberg, Jan

2018-06-22

In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored. To identify virus-host genome interactions and the underlying nuclear landscape for the first time, we combined circular chromosome conformation capture (4C) with RNA-seq and ChIP-seq. Moreover, we studied HBx-binding to HBV episomes. In HBV-positive HepaRG hepatocytes, we observed preferential association of HBV episomes and HBx with actively transcribed nuclear domains on the host genome correlating in size with constrained topological units of chromatin. Interestingly, HBx alone occupied transcribed chromatin domains. Silencing of native HBx caused reduced episomal HBV stability. As part of the HBV episome, HBx might stabilize HBV episomal nuclear localization. Our observations may contribute to the understanding of long-term episomal stability and the facilitation of viral persistence. The exact mechanism by which HBx contributes to HBV nuclear persistence warrants further investigations.

The detection of (total and ccc) HBV DNA in liver transplant recipients with hepatitis B vaccine against HBV reinfection.

PubMed

Duan, Bin-Wei; Lu, Shi-Chun; Lai, Wei; Liu, Xue-En; Liu, Yuan

2015-01-01

To investigate the levels of hepatitis B virus total DNA (HBV DNA) and covalently closed circular (ccc) DNA in liver transplant recipients who received hepatitis B vaccination, including responders and non-responders, following liver transplantation due to hepatitis B-related diseases and to investigate the efficacy of hepatitis B immune reconstitution against HBV reinfection. Twenty responders and 34 non-responders were enrolled in the present study. The levels of HBV total DNA and ccc DNA in peripheral blood mononuclear cells (PBMCs) and the liver and plasma were detected by real-time polymerase chain reaction (PCR). Fifty-three blood samples and 38 liver allograft tissues were acquired. For the responders, the mean serum titer for anti-HBs (antibodies against hepatitis B surface antigen) was 289 (46.64-1000) IU/ml. Also for the responders, HBV total DNA was detected in PBMCs for one recipient and in the liver for another recipient, but ccc DNA was not detected in either of those 2 recipients. For the non-responders, HBV total DNA was detected in PBMCS for 2 recipients, neither of whom had ccc DNA. Also for the non-responders, HBV total DNA was detected in the livers of 3 recipients, 2 of whom also had ccc DNA. All responders had discontinued hepatitis B immunoglobulin (HBIG), and 13 responders had discontinued antiviral agents. One responder experienced HBV recurrence during the follow-up period. For the majority of liver transplant recipients, no HBV total DNA or ccc DNA was detected in the blood or liver. The lack of HBV total DNA and ccc DNA both in PBMCs and the liver in liver transplant recipients who received hepatitis B vaccination to prevent HBV reinfection should be a prerequisite for the withdrawal of HBIG and/or antiviral agents.

Clinical significance of hepatitis B virion and SVP productivity: relationships between intrahepatic and serum markers in chronic hepatitis B patients

PubMed Central

Jackson, Kathy; Lim, Seng Gee; Sulaiman, Ali; Pakasi, Levina S; Gani, Rino A; Hasan, Irsan; Sulaiman, Andri Sanityoso; Lesmana, Laurentius A; Hammond, Rachel; Revill, Peter; Locarnini, Stephen; Bowden, Scott David

2014-01-01

Background Clinical use of hepatitis B viral (HBV) quantitative seromarker\\s remains questionable since it is not precisely known whether they represent intrahepatic viral replication. Covalently closed circular DNA (cccDNA), relaxed circular DNA (rcDNA), and pregenomic RNA (pgRNA) are more likely to represent active HBV replication and their measurement can be used to derive virion productivity (VP; rcDNA/cccDNA), subviral particle (SVP) productivity (quantitative HBsAg/cccDNA), and replicative activity (RA; pgRNA/cccDNA). These can be used to compare relative HBV replication between HBeAg-negative and -positive patients. Objective To study the clinical significance of intrahepatic HBV replication phenomenon between HBeAg-negative and -positive patients and its correlation with quantitative HBV seromarkers. Method This was a prospective study between January 2010 and December 2011. Study subjects were naive chronic hepatitis B patients from Cipto Mangunkusumo and Medistra Hospitals. All patient samples underwent liver biochemistry and HBV seromarkers testing (HBeAg, quantitative HBsAg and HBV DNA levels), and patients underwent liver biopsy. Stored liver specimens were analysed for intrahepatic rcDNA, cccDNA, and pgRNA with quantification performed by real-time PCR. Comparison of HBV markers between HBsAg-positive and -negative patients was carried out using the Mann–Whitney U-test. Pearson’s correlation test was performed among HBV intrahepatic and seromarkers using their log-transformed values. Results A total of 104 patients were enrolled in this study; 54 (51.9%) were male. Patients’ mean age was 41.9 ± 11.63 years (range 19–70 years). Sixty-one patients (58.7%) were HBeAg-negative. All HBV markers were significantly higher in HBeAg-positive than HBeAg-negative patients, except for SVP productivity and RA. Serum HBV DNA was strongly correlated with intrahepatic total HBV DNA (r = 0.771), cccDNA (r = 0.774), and rcDNA (r = 0.780) while serum quantitative HBsAg showed only moderate correlation with intrahepatic total DNA (r = 0.671), cccDNA (r = 0.632), rcDNA (r = 0.675), and SVP productivity (r = 0.557). Conclusions Serum HBV DNA concentration and quantitative HBsAg might not accurately predict intrahepatic viral activity. Virion and SVP production do not occur in parallel with replicative activity. PMID:24918014

SIRT3 restricts HBV transcription and replication via epigenetic regulation of cccDNA involving SUV39H1 and SETD1A histone methyltransferases.

PubMed

Ren, Ji-Hua; Hu, Jie-Li; Cheng, Sheng-Tao; Yu, Hai-Bo; Wong, Vincent Kam Wai; Law, Betty Yuen Kwan; Yang, Yong-Feng; Huang, Ying; Liu, Yi; Chen, Wei-Xian; Cai, Xue-Fei; Tang, Hua; Hu, Yuan; Zhang, Wen-Lu; Liu, Xiang; Long, Quan-Xin; Zhou, Li; Tao, Na-Na; Zhou, Hong-Zhong; Yang, Qiu-Xia; Ren, Fang; He, Lin; Gong, Rui; Huang, Ai-Long; Chen, Juan

2018-04-06

Hepatitis B virus (HBV) infection remains a major health problem worldwide. Maintenance of the covalently closed circular DNA (cccDNA) which serves as a template for HBV RNA transcription is responsible for the failure of eradicating chronic HBV during current antiviral therapy. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications. In this study, we identified SIRT3 as a host factor restricting HBV transcription and replication by screening seven members of Sirtuin family which is the class III histone deacetylase. Ectopic SIRT3 expression significantly reduced total HBV RNAs, 3.5-kb RNA as well as replicative intermediate DNA in HBV-infected HepG2-NTCP cells and PHH. In contrast, gene silencing of SIRT3 promoted HBV transcription and replication. Mechanistic study found nuclear SIRT3 was recruited to the HBV cccDNA, where it deacetylated histone 3 lysine 9 (H3K9). Importantly, occupancy of SIRT3 onto cccDNA could increase the recruitment of histone methyltransferase SUV39H1 to cccDNA and decrease recruitment of SETD1A, leading to a marked increase of H3K9me3 and a decrease of H3K4me3 on cccDNA. Moreover, SIRT3-mediated HBV cccDNA transcriptional repression involved decreased binding of host RNA polymerase II and transcription factor YY1 to cccDNA. Finally, viral protein HBx could relieve SIRT3-mediated cccDNA transcriptional repression by inhibiting both SIRT3 expression and its recruitment to cccDNA. SIRT3 is a novel host factor epigenetically restricting HBV cccDNA transcription by acting cooperatively with histone methyltransferase. These data provided a rational for the use of SIRT3 activators in the prevention or treatment of HBV infection. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Curcumin inhibits hepatitis B virus infection by down-regulating cccDNA-bound histone acetylation.

PubMed

Wei, Zhi-Qiang; Zhang, Yong-Hong; Ke, Chang-Zheng; Chen, Hong-Xia; Ren, Pan; He, Yu-Lin; Hu, Pei; Ma, De-Qiang; Luo, Jie; Meng, Zhong-Ji

2017-09-14

To investigate the potential effect of curcumin on hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and the underlying mechanism. A HepG2.2.15 cell line stably transfected with HBV was treated with curcumin, and HBV surface antigen (HBsAg) and e antigen (HBeAg) expression levels were assessed by ELISA. Intracellular HBV DNA replication intermediates and cccDNA were detected by Southern blot and real-time PCR, respectively. The acetylation levels of histones H3 and H4 were measured by Western blot. H3/H4-bound cccDNA was detected by chromatin immunoprecipitation (ChIP) assays. The deacetylase inhibitors trichostatin A and sodium butyrate were used to study the mechanism of action for curcumin. Additionally, short interfering RNAs (siRNAs) targeting HBV were tested along with curcumin. Curcumin treatment led to time- and dose-dependent reductions in HBsAg and HBeAg expression and significant reductions in intracellular HBV DNA replication intermediates and HBV cccDNA. After treatment with 20 μmol/L curcumin for 2 d, HBsAg and cccDNA levels in HepG2.2.15 cells were reduced by up to 57.7% ( P < 0.01) and 75.5% ( P < 0.01), respectively, compared with levels in non-treated cells. Meanwhile, time- and dose-dependent reductions in the histone H3 acetylation levels were also detected upon treatment with curcumin, accompanied by reductions in H3- and H4-bound cccDNA. Furthermore, the deacetylase inhibitors trichostatin A and sodium butyrate could block the effects of curcumin. Additionally, transfection of siRNAs targeting HBV enhanced the inhibitory effects of curcumin. Curcumin inhibits HBV gene replication via down-regulation of cccDNA-bound histone acetylation and has the potential to be developed as a cccDNA-targeting antiviral agent for hepatitis B.

Inactivation of Hepatitis B Virus Replication in Cultured Cells and In Vivo with Engineered Transcription Activator-Like Effector Nucleases

PubMed Central

Bloom, Kristie; Ely, Abdullah; Mussolino, Claudio; Cathomen, Toni; Arbuthnot, Patrick

2013-01-01

Chronic hepatitis B virus (HBV) infection remains an important global health problem. Stability of the episomal covalently closed circular HBV DNA (cccDNA) is largely responsible for the modest curative efficacy of available therapy. Since licensed anti-HBV drugs have a post-transcriptional mechanism of action, disabling cccDNA is potentially of therapeutic benefit. To develop this approach, we engineered mutagenic transcription activator-like effector nucleases (TALENs) that target four HBV-specific sites within the viral genome. TALENs with cognate sequences in the S or C open-reading frames (ORFs) efficiently disrupted sequences at the intended sites and suppressed markers of viral replication. Following triple transfection of cultured HepG2.2.15 cells under mildly hypothermic conditions, the S TALEN caused targeted mutation in ~35% of cccDNA molecules. Markers of viral replication were also inhibited in vivo in a murine hydrodynamic injection model of HBV replication. HBV target sites within S and C ORFs of the injected HBV DNA were mutated without evidence of toxicity. These findings are the first to demonstrate a targeted nuclease-mediated disruption of HBV cccDNA. Efficacy in vivo also indicates that these engineered nucleases have potential for use in treatment of chronic HBV infection. PMID:23883864

Quantitative intrahepatic HBV cccDNA correlates with histological liver inflammation in chronic hepatitis B virus infection.

PubMed

Liang, Ling-Bo; Zhu, Xia; Yan, Li-Bo; Du, Ling-Yao; Liu, Cong; Liao, Juan; Tang, Hong

2016-11-01

The aim of this study was to determine the role of baseline hepatitis B virus (HBV) forming covalently closed circular DNA (HBV cccDNA) in liver inflammation in patients infected with HBV with serum alanine aminotransferase (ALT) levels under two times the upper limit of normal (2×ULN). After liver biopsy and serum virological and biochemical marker screening, patients diagnosed with chronic HBV infection with serum ALT levels under 2×ULN and histological liver inflammation of less than grade G2 were prospectively recruited into this study. Recruitment took place between March 2009 and November 2010 at the Center of Infectious Disease, Sichuan University. Patient virological and biochemical markers, as well as markers of liver inflammation, were monitored. A total of 102 patients were recruited and 68 met the inclusion criteria; the median follow-up was 4.1 years (range 3.9-5.2 years). During follow-up, 41 patients (60.3%) exhibited signs of inflammation. Baseline HBV cccDNA >1 copy/cell (odds ratio 9.43, p=0.049) and liver inflammation grade ≥G1 (odds ratio 5.77, p=0.046) were both independent predictors of liver inflammation. A higher baseline intrahepatic HBV cccDNA level may increase the risk of liver inflammation. Further investigations will be required to validate HBV cccDNA as an intrahepatic virological marker of patients who require extended outpatient management. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways.

PubMed

Guo, Fang; Zhao, Qiong; Sheraz, Muhammad; Cheng, Junjun; Qi, Yonghe; Su, Qing; Cuconati, Andrea; Wei, Lai; Du, Yanming; Li, Wenhui; Chang, Jinhong; Guo, Ju-Tao

2017-09-01

Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) and sulfamoylbenzamides (SBAs), have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or "empty" capsids devoid of pre-genomic RNA and viral DNA polymerase. Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc) DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm. Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids. Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly. Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B.

Presence of intrahepatic (total and ccc) HBV DNA is not predictive of HBV recurrence after liver transplantation.

PubMed

Hussain, Munira; Soldevila-Pico, Consuelo; Emre, Sukru; Luketic, Velimir; Lok, Anna S F

2007-08-01

Previous studies reported that hepatitis B virus (HBV) deoxyribonucleic acid (DNA) can be detected in livers of patients who received transplants for hepatitis B despite the absence of serological markers of HBV recurrence. Quantification of HBV DNA was not performed and presence of covalently closed circular (ccc) DNA was not analyzed in most studies. We aimed to quantify total and ccc HBV DNA in explant liver and post-orthotopic liver transplantation (OLT) biopsies and to correlate the values with HBV recurrence post-OLT. Frozen liver tissue from 34 patients (9 with explant liver only, 9 with explant liver and post-OLT liver biopsies, and 16 with post-OLT biopsies only) in the National Institutes of Health HBV-OLT study was examined using real-time polymerase chain reaction (PCR). Among the 18 patients with explant liver, 7 were hepatitis B e antigen (HBeAg)-positive, 8 had detectable serum HBV DNA, and 10 received antiviral therapy prior to OLT. Total and ccc HBV DNA was detected in explant livers of 17 and 16 patients, respectively. Of the 10 patients who received antiviral therapy pre-OLT, serum HBV DNA was undetectable in 8 at transplantation but 7 had detectable total and ccc HBV DNA in their explant liver. Of the 25 patients with post-OLT biopsies, total HBV DNA was detected in 83% and ccc DNA in 17% of 47 biopsies, although only 2 patients had HBV recurrence. In conclusion, total and ccc HBV DNA could be detected in explant livers of most patients despite antiviral therapy pre-OLT. Total but not ccc HBV DNA could be detected in post-OLT liver biopsies of most patients despite undetectable serum HBV DNA and hepatitis B surface antigen (HBsAg). Our findings suggest that occult HBV reinfection occurs in most HBV patients after OLT and continued administration of appropriate prophylactic therapy is important in preventing overt HBV recurrence. Copyright (c) 2007 AASLD.

Maturation-Associated Destabilization of Hepatitis B Virus Nucleocapsid

PubMed Central

Cui, Xiuji; Ludgate, Laurie; Ning, Xiaojun

2013-01-01

The mature nucleocapsid (NC) of hepatitis B virus containing the relaxed circular (RC) DNA genome can be secreted extracellularly as virions after envelopment with the viral surface proteins or, alternatively, can be disassembled to release RC DNA (i.e., uncoating) into the host cell nucleus to form the covalently closed circular (CCC) DNA, which sustains viral replication and persistence. In contrast, immature NCs containing the viral single-stranded DNA or the pregenomic RNA are incompetent for either envelopment or uncoating. Little is currently known about how mature NCs, and not the immature ones, are specifically selected for these processes. Here, we have carried out a biochemical analysis of the different NC populations upon their separation through sucrose gradient centrifugation. We have found that the maturation of NCs is associated with their destabilization, manifested as increased protease and nuclease sensitivity, altered sedimentation during sucrose gradient centrifugation, and retarded mobility during native agarose gel electrophoresis. Also, three distinct populations of intracellular mature NCs could be differentiated based on these characteristics. Furthermore, mature NCs generated in vitro under cell-free conditions acquired similar properties. These results have thus revealed significant structural changes associated with NC maturation that likely play a role in the selective uncoating of the mature NC for CCC DNA formation and/or its preferential envelopment for virion secretion. PMID:23966388

Intracellular levels of hepatitis B virus DNA and pregenomic RNA in peripheral blood mononuclear cells of chronically infected patients.

PubMed

Lu, L; Zhang, H-Y; Yueng, Y-H; Cheung, K-F; Luk, J M; Wang, F-S; Lau, G K K

2009-02-01

It remains uncertain whether hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and pregenomic RNA (pgRNA) can be detected in the serum or peripheral blood mononuclear cells (PBMC) of patients with chronic hepatitis B (CHB) infection. We examined HBV cccDNA and pgRNA in the serum and PBMC, and investigated the effect of lamivudine therapy on the viral loads in the PBMC of CHB patients. Paired serum and PBMC samples from 50 treatment-naïve CHB patients [25 hepatitis B e antigen (HBeAg) positive and 25 HBeAg negative] were quantified for total HBV DNA, cccDNA and pgRNA by real time polymerase chain reaction. HBV cccDNA and pgRNA were below the lower detection limit in all serum samples, and in 84% of PBMC. HBV DNA (r = 0.889, P < 0.001) and pgRNA (r = 0.696, P < 0.001) in PBMC correlated with the HBV DNA in serum. In the longitudinal study, 30 patients treated with lamivudine therapy for a median duration of 34 weeks (range 12-48 weeks) were examined. The median HBV DNA reduction in PBMC before and after treatment was 1.318 (range -0.471 to 3.846) log units, which was significantly lower than serum HBV DNA reduction [3.371 (range -0.883 to 9.454) log units, P < 0.05]. HBV cccDNA and pgRNA were undetectable in the serum of CHB patients. HBV viral loads in PBMC correlated with serum HBV DNA. Lamivudine therapy had less effect on the HBV viral loads in PBMC compared with the serum viral loads.

Comparison of Maximum Stretch Forces between Femtosecond Laser-Assisted Capsulotomy and Continuous Curvilinear Capsulorhexis

PubMed Central

Ichikawa, Kei; Tanaka, Yoshiki; Kato, Yukihito; Horai, Rie; Tamaoki, Akeno; Ichikawa, Kazuo

2017-01-01

The current study reports comparing the postoperative mechanical properties of the anterior capsule between femtosecond laser capsulotomy (FLC) and continuous curvilinear capsulorhexis (CCC) of variable size and shape in porcine eyes. All CCCs were created using capsule forceps. Irregular or eccentric CCCs were also created to simulate real cataract surgery. For FLC, capsulotomies 5.3 mm in diameter were created using the LenSx® (Alcon) platform. Fresh porcine eyes were used in all experiments. The edges of the capsule openings were pulled at a constant speed using two L-shaped jigs. Stretch force and distance were recorded over time, and the maximum values in this regard were defined as those that were recorded when the capsule broke. There was no difference in maximum stretch force between CCC and FLC. There were no differences in circularity between FLC and same-sized CCC. However, same-sized CCC did show significantly higher maximum stretch forces than FLC. Teardrop-shaped CCC showed lower maximum stretch forces than same-sized CCC and FLC. Heart-shaped CCC showed lower maximum stretch forces than same-sized CCC. Conclusively, while capsule edge strength after CCC varied depending on size or irregularities, FLC had the advantage of stable maximum stretch forces. PMID:28210504

Comparison of Maximum Stretch Forces between Femtosecond Laser-Assisted Capsulotomy and Continuous Curvilinear Capsulorhexis.

PubMed

Takagi, Mari; Kojima, Takashi; Ichikawa, Kei; Tanaka, Yoshiki; Kato, Yukihito; Horai, Rie; Tamaoki, Akeno; Ichikawa, Kazuo

2017-01-01

The current study reports comparing the postoperative mechanical properties of the anterior capsule between femtosecond laser capsulotomy (FLC) and continuous curvilinear capsulorhexis (CCC) of variable size and shape in porcine eyes. All CCCs were created using capsule forceps. Irregular or eccentric CCCs were also created to simulate real cataract surgery. For FLC, capsulotomies 5.3 mm in diameter were created using the LenSx® (Alcon) platform. Fresh porcine eyes were used in all experiments. The edges of the capsule openings were pulled at a constant speed using two L-shaped jigs. Stretch force and distance were recorded over time, and the maximum values in this regard were defined as those that were recorded when the capsule broke. There was no difference in maximum stretch force between CCC and FLC. There were no differences in circularity between FLC and same-sized CCC. However, same-sized CCC did show significantly higher maximum stretch forces than FLC. Teardrop-shaped CCC showed lower maximum stretch forces than same-sized CCC and FLC. Heart-shaped CCC showed lower maximum stretch forces than same-sized CCC. Conclusively, while capsule edge strength after CCC varied depending on size or irregularities, FLC had the advantage of stable maximum stretch forces.

Human induced pluripotent stem cell-derived hepatic cell lines as a new model for host interaction with hepatitis B virus

PubMed Central

Kaneko, Shun; Kakinuma, Sei; Asahina, Yasuhiro; Kamiya, Akihide; Miyoshi, Masato; Tsunoda, Tomoyuki; Nitta, Sayuri; Asano, Yu; Nagata, Hiroko; Otani, Satoshi; Kawai-Kitahata, Fukiko; Murakawa, Miyako; Itsui, Yasuhiro; Nakagawa, Mina; Azuma, Seishin; Nakauchi, Hiromitsu; Nishitsuji, Hironori; Ujino, Saneyuki; Shimotohno, Kunitada; Iwamoto, Masashi; Watashi, Koichi; Wakita, Takaji; Watanabe, Mamoru

2016-01-01

Hepatitis B virus (HBV) is not eradicated by current antiviral therapies due to persistence of HBV covalently closed circular DNA (cccDNA) in host cells, and thus development of novel culture models for productive HBV infection is urgently needed, which will allow the study of HBV cccDNA eradication. To meet this need, we developed culture models of HBV infection using human induced pluripotent stem cell-derived hepatocyte lineages, including immature proliferating hepatic progenitor-like cell lines (iPS-HPCs) and differentiated hepatocyte-like cells (iPS-Heps). These cells were susceptible to HBV infection, produced HBV particles, and maintained innate immune responses. The infection efficiency of HBV in iPS-HPCs predominantly depended on the expression levels of sodium taurocholate cotransporting polypeptide (NTCP), and was low relative to iPS-Heps: however, long-term culture of iPS-Heps was difficult. To provide a model for HBV persistence, iPS-HPCs overexpressing NTCP were established. The long-term persistence of HBV cccDNA was detected in iPS-HPCs overexpressing NTCP, and depended on the inhibition of the Janus-kinase signaling pathway. In conclusion, this study provides evidence that iPS-derived hepatic cell lines can be utilized for novel HBV culture models with genetic variation to investigate the interactions between HBV and host cells and the development of anti-HBV strategies. PMID:27386799

Simple and Reliable Method to Quantify the Hepatitis B Viral Load and Replicative Capacity in Liver Tissue and Blood Leukocytes

PubMed Central

Minosse, Claudia; Coen, Sabrina; Visco Comandini, Ubaldo; Lionetti, Raffaella; Montalbano, Marzia; Cerilli, Stefano; Vincenti, Donatella; Baiocchini, Andrea; Capobianchi, Maria R.; Menzo, Stefano

2016-01-01

Background A functional cure of chronic hepatitis B (CHB) is feasible, but a clear view of the intrahepatic viral dynamics in each patient is needed. Intrahepatic covalently closed circular DNA (cccDNA) is the stable form of the viral genome in infected cells, and represents the ideal marker of parenchymal colonization. Its relationships with easily accessible peripheral parameters need to be elucidated in order to avoid invasive procedures in patients. Objectives The goal of this study was to design, set up, and validate a reliable and straightforward method for the quantification of the cccDNA and total DNA of the hepatitis B virus (HBV) in a variety of clinical samples. Patients and Methods Clinical samples from a cohort of CHB patients, including liver biopsies in some, were collected for the analysis of intracellular HBV molecular markers using novel molecular assays. Results A plasmid construct, including sequences from the HBV genome and from the human gene hTERT, was generated as an isomolar multi-standard for HBV quantitation and normalization to the cellular contents. The specificity of the real-time assay for the cccDNA was assessed using Dane particles isolated on a density gradient. A comparison of liver tissue from 6 untreated and 6 treated patients showed that the treatment deeply reduced the replicative capacity (total DNA/cccDNA), but had limited impact on the parenchymal colonization. The peripheral blood mononuclear cells (PBMCs) and granulocytes from the treated and untreated patients were also analyzed. Conclusions A straightforward method for the quantification of intracellular HBV molecular parameters in clinical samples was developed and validated. The widespread use of such versatile assays could better define the prognosis of CHB, and allow a more rational approach to time-limited tailored treatment strategies. PMID:27882060

Inhibitory effects of crude extracts from some edible Thai plants against replication of hepatitis B virus and human liver cancer cells

PubMed Central

2012-01-01

Background Edible plants such as Cratoxylum formosum (Jack) Dyer, Curcumin longa Lin, Momordica charantia Lin and Moringa oleifera Lam have long been believed in Thai culture to relieve ulcers and the symptoms of liver disease. However, little is known about their anti-liver cancer properties and antiviral activity against hepatitis B virus (HBV). The aim of this study was to investigate the anti-liver cancer and anti-HBV activities of crude extracts from these edible plants on human liver cancer cells. Methods Plant samples were prepared and extracted using buffer and hydro-alcoholic solvents. The MTT assay was performed to investigate the effects of the plant extracts on the cell viability of HepG2 cells. The inhibitory effect on replication of HBV was analysed by determining the level of HBV covalently closed circular DNA (cccDNA) in transiently transfected HepG2 cells with the DNA expression plasmid of the HBV genome using a quantitative real-time PCR. Results Buffer and hydroalcoholic extracts from C. formosum (leaf) reduced cell viability of HepG2 cells and they also inhibited HBV cccDNA. Crude extracts from C. longa (bulb) in both solvents did not have any cytotoxic effects on the HepG2 cells, but they significantly decreased the level of HBV cccDNA. Buffer extracts from the leaves of M. charantia and the fruits of M. oleifera showed to have anti-HBV activity and also a mild cytotoxicity effect on the HepG2 cells. In addition, leaves of M. Oleifera extracted by hydroalcoholic solvent drastically decreased the level of cccDNA in transiently transfected HepG2 cells. Conclusion Some crude extracts of edible plants contain compounds that demonstrate anti-liver cancer and anti-HBV activities. PMID:23216691

Deep sequencing shows low-level oncogenic hepatitis B virus variants persists post-liver transplant despite potent anti-HBV prophylaxis.

PubMed

Lau, K C K; Osiowy, C; Giles, E; Lusina, B; van Marle, G; Burak, K W; Coffin, C S

2018-06-01

Recent studies suggest that withdrawal of hepatitis B immune globulin (HBIG) and nucleos(t)ide analogues (NA) prophylaxis may be considered in HBV surface antigen (HBsAg)-negative liver transplant (LT) recipients with a low risk of disease recurrence. However, the frequency of occult HBV infection (OBI) and HBV variants after LT in the current era of potent NA therapy is unknown. Twelve LT recipients on prophylaxis were tested in matched plasma and peripheral blood mononuclear cells (PBMCs) for HBV quasispecies by in-house nested PCR and next-generation sequencing of amplicons. HBV covalently closed circular DNA (cccDNA) was detected in Hirt DNA isolated from PBMCs with cccDNA-specific primers and confirmed by nucleic acid hybridization and Sanger sequencing. HBV mRNA in PBMC was detected with reverse-transcriptase nested PCR. In LT recipients on immunosuppressive therapy (10/12 male; median age 57.5 [IQR: 39.8-66.5]; median follow-up post-LT 60 months; 6 pre-LT hepatocellular carcinoma [HCC]), 9 were HBsAg-. HBV DNA was detected in all plasma and PBMC tested; cccDNA and/or mRNA was detected in the PBMC of 10/12 patients. Significant HBV quasispecies diversity (ie 143-2212 nonredundant HBV species) was noted in both sites, and single nucleotide polymorphisms associated with cirrhosis and HCC were detected at varying frequencies. In conclusion, OBI and HBV variants associated with severe liver disease persist in LT recipients on prophylaxis. Although HBV control and cccDNA transcriptional silencing may occur despite immunosuppression, complete virological eradication does not occur in LT recipients with a history of HBV-related end-stage liver disease. © 2018 John Wiley & Sons Ltd.

Continuous circular cycling as a predictor of treatment response in bipolar disorders: a comprehensive review of the current literature.

PubMed

Tundo, Antonio; Cavalieri, Paola

2018-02-01

Evidence from the literature suggests that, on average, 27% of patients with a bipolar disorder (BD) experience a continuous cycling course (CCC) and that this subgroup differs significantly from patients with a noncontinuous cycling course (N-CCC) with respect to sociodemographic characteristics and clinical presentation. The aim of the present paper is to review the studies that evaluated short- and long-term treatment responses in BD patients with CCC. The retrieved studies indicate that CCC is a significant predictor of poor response to long-term treatment with lithium (the odds of a response in the CCC group were 57% less than in the N-CCC group; p<0.01), as well as to polytherapies including lithium and/or an antiepileptic augmented, when necessary, with an antipsychotic and/or antidepressant. The percentage of patients without new episodes during follow-up was significantly lower in the CCC group compared with the N-CCC group (15.4 vs. 37.6% , p<0.01). Compared with patients in the N-CCC group, members of the CCC group had a poorer response and lower remission rates after 12-week antidepressant treatments for a major depressive episode (82.3 vs. 50%, p =0.002; 69.6 vs. 40.9%, p=0.013). These findings, underlining that CCC is a predictor of poor response to short- and long-term treatment in BD, should be interpreted considering the limitations of the reviewed studies (the small sample sizes, the small number of trials and their observational nature, the lack of randomization or placebo controls, and the unblinded nature of the outcomes). Clinical trials and observational studies with larger samples are warranted to confirm the conclusions of our review.

NTCP-Reconstituted In Vitro HBV Infection System.

PubMed

Sun, Yinyan; Qi, Yonghe; Peng, Bo; Li, Wenhui

2017-01-01

Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a functional receptor for hepatitis B virus (HBV). Expressing human NTCP in human hepatoma HepG2 cells (HepG2-NTCP) renders these cells susceptible for HBV infection. The HepG2-NTCP stably transfected cell line provides a much-needed and easily accessible platform for studying the virus. HepG2-NTCP cells could also be used to identify chemicals targeting key steps of the virus life cycle including HBV covalent closed circular (ccc) DNA, and enable the development of novel antivirals against the infection.Many factors may contribute to the efficiency of HBV infection on HepG2-NTCP cells, with clonal differences among cell line isolates, the source of viral inoculum, and infection medium among the most critical ones. Here, we provide detailed protocols for efficient HBV infection of HepG2-NTCP cells in culture; generation and selection of single cell clones of HepG2-NTCP; production of infectious HBV virion stock through DNA transfection of recombinant plasmid that enables studying primary clinical HBV isolates; and assessing the infection with immunostaining of HBV antigens and Southern blot analysis of HBV cccDNA.

Comparative study on the mechanical mechanism of confined concrete supporting arches in underground engineering.

PubMed

Lv, Zhijin; Qin, Qian; Jiang, Bei; Luan, Yingcheng; Yu, Hengchang

2018-01-01

In order to solve the supporting problem in underground engineering with high stress, square steel confined concrete (SQCC) supporting method is adopted to enhance the control on surrounding rocks, and the control effect is remarkable. The commonly used cross section shapes of confined concrete arch are square and circular. At present, designers have no consensus on which kind is more proper. To search for the answer, this paper makes an analysis on the mechanical properties of the two shapes of the cross-sections. A full-scale indoor comparative test was carried out on the commonly used straight-wall semi-circular SQCC arch and circular steel confined concrete arch (CCC arch). This test is based on self-developed full-scale test system for confined concrete arch. Our research, combining with the numerical analysis, shows: (1) SQCC arch is consistent with CCC arch in the deformation and failure mode. The largest damages parts are at the legs of both of them. (2) The SQCC arch's bearing capability is 1286.9 kN, and the CCC arch's ultimate bearing capability is 1072.4kN. Thus, the SQCC arch's bearing capability is 1.2 times that of the CCC arch. (3) The arches are subjected to combined compression and bending, bending moment is the main reason for the arch failure. The section moment of inertia of SQCC arch is 1.26 times of that of CCC arch, and the former is better than the latter in bending performance. The ultimate bearing capacity is positively correlated with the size of the moment of inertia. Based on the above research, the engineering suggestions are as follows: (1) To improve the bearing capacity of the arch, the cross-sectional shape of the chamber should be optimized and the arch bearing mode changed accordingly. (2) The key damaged positions, such as the arch leg, should be reinforced, optimizing the state of force on the arch. SQCC arches should be used for supporting in underground engineering, which is under stronger influence of the bending moment and non-uniform load on the supporting arches. The research results could provide a theoretical basis for the design of confined concrete support in underground engineering.

Comparative study on the mechanical mechanism of confined concrete supporting arches in underground engineering

PubMed Central

Qin, Qian; Jiang, Bei; Luan, Yingcheng; Yu, Hengchang

2018-01-01

In order to solve the supporting problem in underground engineering with high stress, square steel confined concrete (SQCC) supporting method is adopted to enhance the control on surrounding rocks, and the control effect is remarkable. The commonly used cross section shapes of confined concrete arch are square and circular. At present, designers have no consensus on which kind is more proper. To search for the answer, this paper makes an analysis on the mechanical properties of the two shapes of the cross-sections. A full-scale indoor comparative test was carried out on the commonly used straight-wall semi-circular SQCC arch and circular steel confined concrete arch (CCC arch). This test is based on self-developed full-scale test system for confined concrete arch. Our research, combining with the numerical analysis, shows: (1) SQCC arch is consistent with CCC arch in the deformation and failure mode. The largest damages parts are at the legs of both of them. (2) The SQCC arch’s bearing capability is 1286.9 kN, and the CCC arch’s ultimate bearing capability is 1072.4kN. Thus, the SQCC arch’s bearing capability is 1.2 times that of the CCC arch. (3) The arches are subjected to combined compression and bending, bending moment is the main reason for the arch failure. The section moment of inertia of SQCC arch is 1.26 times of that of CCC arch, and the former is better than the latter in bending performance. The ultimate bearing capacity is positively correlated with the size of the moment of inertia. Based on the above research, the engineering suggestions are as follows: (1) To improve the bearing capacity of the arch, the cross-sectional shape of the chamber should be optimized and the arch bearing mode changed accordingly. (2) The key damaged positions, such as the arch leg, should be reinforced, optimizing the state of force on the arch. SQCC arches should be used for supporting in underground engineering, which is under stronger influence of the bending moment and non-uniform load on the supporting arches. The research results could provide a theoretical basis for the design of confined concrete support in underground engineering. PMID:29447187

Precision Pulse Capsulotomy: Preclinical Safety and Performance of a New Capsulotomy Technology.

PubMed

Chang, David F; Mamalis, Nick; Werner, Liliana

2016-02-01

To assess the preclinical safety and performance of a new precision pulse capsulotomy (PPC) method. Human cadaver eye studies and surgical, slit-lamp, and histopathologic evaluation in a consecutive series of 20 live rabbits. Human cadaver eyes and New Zealand white rabbits. Precision pulse capsulotomy uses a highly focused, fast, multipulse, low-energy discharge to produce a perfectly round anterior capsulotomy instantaneously and simultaneously along all 360°. Capsulotomies are performed using a disposable handpiece with a soft collapsible tip and circular nitinol cutting element. Miyake-Apple imaging and scanning electron microscopy (SEM) of PPC were conducted in human cadaver eyes. Surgical, postoperative slit-lamp, and histopathologic assessments of PPC were performed in 20 live rabbits and were compared with manual continuous curvilinear capsulorrhexis (CCC) in the fellow eye. Anterior chamber (AC) thermocouple temperature measurements were evaluated in a subset of rabbit eyes. Capsulotomy edge circularity, SEM morphologic features and zonular movement with PPC in human cadaver eyes. Anterior chamber temperature during PPC and grading of ocular inflammation, corneal endothelial damage, anterior capsular opacification (ACO), and posterior capsular opacification (PCO). Miyake-Apple imaging showed minimal zonular stress, and thermocouple measurements demonstrated negligible AC temperature changes during PPC. Precision pulse capsulotomy produced round, complete capsulotomies in all 20 rabbit eyes, leading to successful in-the-bag intraocular lens (IOL) implantation. Slit-lamp examinations at 3 days and 1, 2, and 4 weeks after surgery showed no significant differences between PPC and CCC in corneal edema, AC inflammatory reaction, capsular fibrosis, ACO, and PCO. Postmortem studies showed no difference in the corneal endothelium between PPC and CCC eyes. All IOLs were well centered in PPC eyes, and histopathologic analysis showed no greater inflammatory infiltrates. Precision pulse capsulotomy is a new method to automate consistent creation of a perfectly circular anterior capsulotomy with a disposable handheld instrument that can be used in the normal phacoemulsification surgical sequence. Compared with CCC in fellow rabbit eyes, PPC was equally safe and showed no greater zonular stress compared with CCC in human cadaver eyes. Human cadaver eye SEM showed a much smoother capsulotomy edge compared to those produced by femtosecond laser. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Open chest cardiac massage offers no benefit over closed chest compressions in patients with traumatic cardiac arrest.

PubMed

Bradley, Matthew J; Bonds, Brandon W; Chang, Luke; Yang, Shiming; Hu, Peter; Li, Hsiao-Chi; Brenner, Megan L; Scalea, Thomas M; Stein, Deborah M

2016-11-01

Open chest cardiac massage (OCCM) is a commonly performed procedure after traumatic cardiac arrest (TCA). OCCM has been reported to be superior to closed chest compressions (CCC) in animal models and in non-TCA. The purpose of this study is to prospectively compare OCCM versus CCC in TCA using end-tidal carbon dioxide (ETCO2), the criterion standard for determining the effectiveness of chest compressions and detection of return of spontaneous circulation (ROSC), as the surrogate for cardiac output and marker for adequacy of resuscitation. This prospective observational study enrolled patients over a 9-month period directly presenting to a level 1 trauma center after TCA. Continuous high-resolution ETCO2 measurements were collected every 6 seconds for periods of CCC and OCCM, respectively. Patients receiving CCC only were compared with patients receiving CCC followed by OCCM. Student's t tests were used to compare ETCO2 within and between groups. Thirty-three patients were enrolled (16 OCCM, 17 CCC-only). Mean time of CCC before OCCM was 66 seconds. Within the OCCM group, final, peak, mean, and median ETCO2 levels significantly increased when comparing the initial CCC period to the OCCM interval. Using a time-matched comparison, significant increases were observed in the final and peak but not mean and median values when comparing the first minute of CCC to the remaining time in the CCC-only group. However, when periods of OCCM were compared with equivalent periods of CCC-only, there were no differences in the initial, final, peak, mean, or median ETCO2 values. Correspondingly, no difference in rates of ROSC was observed between groups (OCCM 23.5% vs. CCC 38.9%; p = 0.53). Although we could not control for confounders, we found no significant improvement in ETCO2 or ROSC with OCCM. With newer endovascular techniques for aortic occlusion, thoracotomy solely for performing OCCM provides no benefit over CCC. Therapeutic study, level III.

Decay of ccc-DNA marks persistence of intrahepatic viral DNA synthesis under tenofovir in HIV-HBV co-infected patients.

PubMed

Boyd, Anders; Lacombe, Karine; Lavocat, Fabien; Maylin, Sarah; Miailhes, Patrick; Lascoux-Combe, Caroline; Delaugerre, Constance; Girard, Pierre-Marie; Zoulim, Fabien

2016-10-01

In the presence of highly-potent antivirals, persistence of hepatitis B virus (HBV) is most well-characterized by covalently-closed circular DNA (cccDNA) and total intrahepatic DNA (IH-DNA). We sought to determine how antiviral therapy could affect their levels during human immunodeficiency virus (HIV)-HBV co-infection. Sixty co-infected patients from a well-defined cohort with ⩾1 liver biopsy were studied. HBV cccDNA and total IH-DNA were extracted from biopsies and quantified by real-time PCR. Factors associated with intrahepatic viral load were determined using mixed-effect linear regression and half-life viral kinetics during reconstructed follow-up using non-linear exponential decay models. At biopsy, 35 (58.3%) patients were hepatitis B "e" antigen (HBeAg)-positive and 33 (55.0%) had detectable plasma HBV-DNA (median=4.58log10IU/ml, IQR=2.95-7.43). Overall, median cccDNA was -0.95log10copies/cell (IQR=-1.70, -0.17) and total IH-DNA was 0.27log10copies/cell (IQR=-0.39, 2.00). In multivariable analysis, significantly lower levels of cccDNA and total IH-DNA were observed in patients with HBeAg-negative serology, nadir CD4(+) cell counts >250/mm(3), and longer cumulative TDF-duration, but not lamivudine- or adefovir-duration. In post-hoc analysis using reconstructed TDF-duration (median 29.6months, IQR=15.0-36.1, n=31), average half-life of cccDNA was estimated at 9.2months (HBeAg-positive=8.6, HBeAg-negative=26.2) and total IH DNA at 5.8months (HBeAg-positive=1.3, HBeAg-negative=13.6). Intrahepatic viral loads remained detectable for all patients, even with prolonged TDF-exposure. In co-infection, TDF-use is associated with lower levels of HBV replication intermediates and cccDNA. Slow decay of intrahepatic viral loads underscores that TDF is unable to completely block intracellular viral DNA synthesis, which possibly accounts for continuous replenishment of the cccDNA pool. Chronic hepatitis B virus (HBV) is a persistent infection, while the only real way of knowing the extent of this persistence is through measuring levels of virus in the liver. In this study, we examine levels of HBV in the liver among patients with both HBV and human immunodeficiency virus, or HIV, infection. It would appear that the currently available medication, namely "tenofovir", works well to decrease virus levels in the liver, but it remains at low levels despite long periods of treatment. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Advances with using CRISPR/Cas-mediated gene editing to treat infections with hepatitis B virus and hepatitis C virus.

PubMed

Moyo, Buhle; Bloom, Kristie; Scott, Tristan; Ely, Abdullah; Arbuthnot, Patrick

2018-01-15

Chronic infections with hepatitis B and hepatitis C viruses (HBV and HCV) account for the majority of cases of cirrhosis and hepatocellular carcinoma. Current therapies for the infections have limitations and improved efficacy is necessary to prevent complications in carriers of the viruses. In the case of HBV persistence, the replication intermediate comprising covalently closed circular DNA (cccDNA) is particularly problematic. Licensed therapies have little effect on cccDNA and HBV replication relapses following treatment withdrawal. Disabling cccDNA is thus key to curing HBV infections and application of gene editing technology, such as harnessing the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, has curative potential. Several studies have reported good efficacy when employing CRISPR/Cas technologies to disable HBV replication in cultured cells and in hydrodynamically injected mice. Recent advances with HCV drug development have revolutionized treatment of the infection. Nevertheless, individuals may be refractory to treatment. Targeting RNA from HCV with CRISPR/Cas isolated from Francisella novicida may have therapeutic utility. Although preclinical work shows that CRISPR/Cas technology has potential to overcome infection with HBV and HCV, significant challenges need to be met. Ensuring specificity for viral targets and efficient delivery of the gene editing sequences to virus-infected cells are particularly important. The field is at an interesting stage and the future of curative antiviral drug regimens, particularly for treatment of chronic HBV infection, may well entail use of combinations that include derivatives of CRISPR/Cas. Copyright © 2017 Elsevier B.V. All rights reserved.

Core-shell magnetite-silica composite nanoparticles enhancing DNA damage induced by a photoactive platinum-diimine complex in red light.

PubMed

Zhang, Zhigang; Chai, Aiyun

2012-12-01

Lack of solubility under physiological conditions poses an additional risk for toxicity and side effects for intravenous delivery of the photodynamic therapeutic agent in vivo. Employing magnetite-silica composite nanoparticles as carriers of the photodynamic therapeutic agents may be a promising way to solve the problem. In this study, core-shell magnetite-silica composite nanoparticles were prepared by a sol-gel method, and characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy and dynamic light scattering, then they were used as carriers of a photoactive platinum diimine complex. The interactions of the photosensitizer-loaded magnetic composite nanoparticles with DNA in red light were monitored by agarose-gel electrophoresis. The results suggest that high doses of magnetite-silica composite nanoparticles might facilitate the transformation of covalently closed circular (ccc)-DNA band to open circular (oc)-DNA band though they are harmless to DNA at their low concentrations, therefore enhancing the extent of DNA damage caused by the metal complex in red light. Copyright © 2012 Elsevier Inc. All rights reserved.

Construction and characterization of an in-vivo linear covalently closed DNA vector production system.

PubMed

Nafissi, Nafiseh; Slavcev, Roderick

2012-12-06

While safer than their viral counterparts, conventional non-viral gene delivery DNA vectors offer a limited safety profile. They often result in the delivery of unwanted prokaryotic sequences, antibiotic resistance genes, and the bacterial origins of replication to the target, which may lead to the stimulation of unwanted immunological responses due to their chimeric DNA composition. Such vectors may also impart the potential for chromosomal integration, thus potentiating oncogenesis. We sought to engineer an in vivo system for the quick and simple production of safer DNA vector alternatives that were devoid of non-transgene bacterial sequences and would lethally disrupt the host chromosome in the event of an unwanted vector integration event. We constructed a parent eukaryotic expression vector possessing a specialized manufactured multi-target site called "Super Sequence", and engineered E. coli cells (R-cell) that conditionally produce phage-derived recombinase Tel (PY54), TelN (N15), or Cre (P1). Passage of the parent plasmid vector through R-cells under optimized conditions, resulted in rapid, efficient, and one step in vivo generation of mini lcc--linear covalently closed (Tel/TelN-cell), or mini ccc--circular covalently closed (Cre-cell), DNA constructs, separated from the backbone plasmid DNA. Site-specific integration of lcc plasmids into the host chromosome resulted in chromosomal disruption and 10(5) fold lower viability than that seen with the ccc counterpart. We offer a high efficiency mini DNA vector production system that confers simple, rapid and scalable in vivo production of mini lcc DNA vectors that possess all the benefits of "minicircle" DNA vectors and virtually eliminate the potential for undesirable vector integration events.

Plant Cation-Chloride Cotransporters (CCC): Evolutionary Origins and Functional Insights.

PubMed

Henderson, Sam W; Wege, Stefanie; Gilliham, Matthew

2018-02-06

Genomes of unicellular and multicellular green algae, mosses, grasses and dicots harbor genes encoding cation-chloride cotransporters (CCC). CCC proteins from the plant kingdom have been comparatively less well investigated than their animal counterparts, but proteins from both plants and animals have been shown to mediate ion fluxes, and are involved in regulation of osmotic processes. In this review, we show that CCC proteins from plants form two distinct phylogenetic clades (CCC1 and CCC2). Some lycophytes and bryophytes possess members from each clade, most land plants only have members of the CCC1 clade, and green algae possess only the CCC2 clade. It is currently unknown whether CCC1 and CCC2 proteins have similar or distinct functions, however they are both more closely related to animal KCC proteins compared to NKCCs. Existing heterologous expression systems that have been used to functionally characterize plant CCC proteins, namely yeast and Xenopus laevis oocytes, have limitations that are discussed. Studies from plants exposed to chemical inhibitors of animal CCC protein function are reviewed for their potential to discern CCC function in planta. Thus far, mutations in plant CCC genes have been evaluated only in two species of angiosperms, and such mutations cause a diverse array of phenotypes-seemingly more than could simply be explained by localized disruption of ion transport alone. We evaluate the putative roles of plant CCC proteins and suggest areas for future investigation.

Plant Cation-Chloride Cotransporters (CCC): Evolutionary Origins and Functional Insights

PubMed Central

Gilliham, Matthew

2018-01-01

Genomes of unicellular and multicellular green algae, mosses, grasses and dicots harbor genes encoding cation-chloride cotransporters (CCC). CCC proteins from the plant kingdom have been comparatively less well investigated than their animal counterparts, but proteins from both plants and animals have been shown to mediate ion fluxes, and are involved in regulation of osmotic processes. In this review, we show that CCC proteins from plants form two distinct phylogenetic clades (CCC1 and CCC2). Some lycophytes and bryophytes possess members from each clade, most land plants only have members of the CCC1 clade, and green algae possess only the CCC2 clade. It is currently unknown whether CCC1 and CCC2 proteins have similar or distinct functions, however they are both more closely related to animal KCC proteins compared to NKCCs. Existing heterologous expression systems that have been used to functionally characterize plant CCC proteins, namely yeast and Xenopus laevis oocytes, have limitations that are discussed. Studies from plants exposed to chemical inhibitors of animal CCC protein function are reviewed for their potential to discern CCC function in planta. Thus far, mutations in plant CCC genes have been evaluated only in two species of angiosperms, and such mutations cause a diverse array of phenotypes—seemingly more than could simply be explained by localized disruption of ion transport alone. We evaluate the putative roles of plant CCC proteins and suggest areas for future investigation. PMID:29415511

Two-Centre Convergent Close-Coupling Approach to Ion-Atom Collisions: Current Progress

NASA Astrophysics Data System (ADS)

Kadyrov, Alisher; Abdurakhmanov, Ilkhom; Bailey, Jackson; Bray, Igor

2016-09-01

There are two versions of the convergent close-coupling (CCC) approach to ion-atom collisions: quantum-mechanical (QM-CCC) and semi-classical (SC-CCC). Recently, both implementations have been extended to include electron-transfer channels. The SC-CCC approach has been applied to study the excitation and the electron-capture processes in proton-hydrogen collisions. The integral alignment parameter A20 for polarization of Lyman- α emission and the cross sections for excitation and electron-capture into the lowest excited states have been calculated for a wide range of the proton impact energies. It has been established that for convergence of the results a very wide range of impact parameters (typically, 0-50 a.u.) is required due to extremely long tails of transition probabilities for transitions into the 2 p states at high energies. The QM-CCC approach allowed to obtain an accurate solution of proton-hydrogen scattering problem including all underlying processes, namely, direct scattering and ionisation, and electron capture into bound and continuum states of the projectile. In this presentation we give a general overview of current progress in applications of the two-centre CCC approach to ion-atom and atom-atom collisions. The work is supported by the Australian Research Council.

Electron- and positron-molecule scattering: development of the molecular convergent close-coupling method

NASA Astrophysics Data System (ADS)

Zammit, Mark C.; Fursa, Dmitry V.; Savage, Jeremy S.; Bray, Igor

2017-06-01

Starting from first principles, this tutorial describes the development of the adiabatic-nuclei convergent close-coupling (CCC) method and its application to electron and (single-centre) positron scattering from diatomic molecules. We give full details of the single-centre expansion CCC method, namely the formulation of the molecular target structure; solving the momentum-space coupled-channel Lippmann-Schwinger equation; deriving adiabatic-nuclei cross sections and calculating V-matrix elements. Selected results are presented for electron and positron scattering from molecular hydrogen H2 and electron scattering from the vibrationally excited molecular hydrogen ion {{{H}}}2+ and its isotopologues (D2 +, {{{T}}}2+, HD+, HT+ and TD+). Convergence in both the close-coupling (target state) and projectile partial-wave expansions of fixed-nuclei electron- and positron-molecule scattering calculations is demonstrated over a broad energy-range and discussed in detail. In general, the CCC results are in good agreement with experiments.

Clinical results of the open ring PMMA guider assisted capsulorrhexis in cataract surgery.

PubMed

Lee, Jee Hye; Lee, Yong Eun; Joo, Choun-Ki

2018-05-10

To compare the results of continuous curvilinear capsulorrhexis(CCC) after application of an open ring-shaped guider compared with a free-hand procedure in eyes with cataracts. This study comprised patients undergoing cataract surgery in Seoul St.Mary's Hospital, The Catholic University of Korea. Eyes were grouped depending on the capsulotomy method; CCC was performed by free-hand procedure on 94 eyes (free-hand group), and it was performed under the guidance after introduction of an open ring-shaped guider on consecutive 89 eyes (guided group). Horizontal and vertical diameter, area and circularity of capsulotomy were measured postoperatively at one day, two months and six months. Differences in parameters and the percentage of ideal capsulorrhexis were analyzed between the two groups. On the first postoperative day, the vertical diameter in the guided group (5.24 ± 0.16 mm) was significantly longer than that of the free-hand group (5.01 ± 0.65 mm, P = 0.019). The area of capsulotomy was larger in the guided group (21.55 ± 0.87 mm 2 ) than that of the free-hand group (20.34 ± 2.96 mm 2 , P < 0.001). Circularity in the guided group (0.84 ± 0.03), was significantly greater than that of the free-hand group (0.69 ± 0.17, P = 0.036). Ideal capsulorrhexis was obtained in 60 eyes (67%) in the free-hand group and 81 eyes (86%) in the guided group. After introduction of an open ring-shaped guider, CCC became larger and more circular with less anterior capsular contracture. The rate of acquiring ideal capsulorrhexis was higher in the guided group than it was in the free-hand group for six months after surgery.

In vitro and in vivo infectivity and pathogenicity of the lymphoid cell-derived woodchuck hepatitis virus.

PubMed

Lew, Y Y; Michalak, T I

2001-02-01

Woodchuck hepatitis virus (WHV) and human hepatitis B virus are closely related, highly hepatotropic mammalian DNA viruses that also replicate in the lymphatic system. The infectivity and pathogenicity of hepadnaviruses propagating in lymphoid cells are under debate. In this study, hepato- and lymphotropism of WHV produced by naturally infected lymphoid cells was examined in specifically established woodchuck hepatocyte and lymphoid cell cultures and coculture systems, and virus pathogenicity was tested in susceptible animals. Applying PCR-based assays discriminating between the total pool of WHV genomes and covalently closed circular DNA (cccDNA), combined with enzymatic elimination of extracellular viral sequences potentially associated with the cell surface, our study documents that virus replicating in woodchuck lymphoid cells is infectious to homologous hepatocytes and lymphoid cells in vitro. The productive replication of WHV from lymphoid cells in cultured hepatocytes was evidenced by the appearance of virus-specific DNA, cccDNA, and antigens, transmissibility of the virus through multiple passages in hepatocyte cultures, and the ability of the passaged virus to infect virus-naive animals. The data also revealed that WHV from lymphoid cells can initiate classical acute viral hepatitis in susceptible animals, albeit small quantities (approximately 10(3) virions) caused immunovirologically undetectable (occult) WHV infection that engaged the lymphatic system but not the liver. Our results provide direct in vitro and in vivo evidence that lymphoid cells in the infected host support propagation of infectious hepadnavirus that has the potential to induce hepatitis. They also emphasize a principal role of the lymphatic system in the maintenance and dissemination of hepadnavirus infection, particularly when infection is induced by low virus doses.

HBV Bypasses the Innate Immune Response and Does Not Protect HCV From Antiviral Activity of Interferon.

PubMed

Mutz, Pascal; Metz, Philippe; Lempp, Florian A; Bender, Silke; Qu, Bingqian; Schöneweis, Katrin; Seitz, Stefan; Tu, Thomas; Restuccia, Agnese; Frankish, Jamie; Dächert, Christopher; Schusser, Benjamin; Koschny, Ronald; Polychronidis, Georgios; Schemmer, Peter; Hoffmann, Katrin; Baumert, Thomas F; Binder, Marco; Urban, Stephan; Bartenschlager, Ralf

2018-05-01

Hepatitis C virus (HCV) infection is sensitive to interferon (IFN)-based therapy, whereas hepatitis B virus (HBV) infection is not. It is unclear whether HBV escapes detection by the IFN-mediated immune response or actively suppresses it. Moreover, little is known on how HBV and HCV influence each other in coinfected cells. We investigated interactions between HBV and the IFN-mediated immune response using HepaRG cells and primary human hepatocytes (PHHs). We analyzed the effects of HBV on HCV replication, and vice versa, at the single-cell level. PHHs were isolated from liver resection tissues from HBV-, HCV-, and human immunodeficiency virus-negative patients. Differentiated HepaRG cells overexpressing the HBV receptor sodium taurocholate cotransporting polypeptide (dHepaRGNTCP) and PHHs were infected with HBV. Huh7.5 cells were transfected with circular HBV DNA genomes resembling viral covalently closed circular DNA (cccDNA), and subsequently infected with HCV; this served as a model of HBV and HCV coinfection. Cells were incubated with IFN inducers, or IFNs, and antiviral response and viral replication were analyzed by immune fluorescence, reverse-transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assays, and flow cytometry. HBV infection of dHepaRGNTCP cells and PHHs neither activated nor inhibited signaling via pattern recognition receptors. Incubation of dHepaRGNTCP cells and PHHs with IFN had little effect on HBV replication or levels of cccDNA. HBV infection of these cells did not inhibit JAK-STAT signaling or up-regulation of IFN-stimulated genes. In coinfected cells, HBV did not prevent IFN-induced suppression of HCV replication. In dHepaRGNTCP cells and PHHs, HBV evades the induction of IFN and IFN-induced antiviral effects. HBV infection does not rescue HCV from the IFN-mediated response. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Command, Control and Communications Capabilities Enabling 21st Century Missions, a Historical Perspective

NASA Technical Reports Server (NTRS)

Waterman, Robert D.; Rice, Herbert D.; Waterman, Susan J.

2010-01-01

Command, Control and Communications (CCC) has evolved through the years from simple switches, dials, analogue hardwire networks and lights to a modern computer based digital network. However there are two closely coupled pillars upon which a CCC system is built. The first, is that technology drives the pace of advancement. The second is that a culture that fosters resistance to change can limit technological advancements in the CCC system. While technology has advanced at a tremendous rate throughout the years, the change in culture has moved slowly. This paper will attempt to show through a historical perspective where specific design decisions for early CCC systems have erroneously evolved into general requirements being imposed on later systems. Finally this paper will provide a glimpse into the future directions envisioned for CCC capabilities that will enable 21st century missions.

Analysis of Femtosecond Laser Assisted Capsulotomy Cutting Edges and Manual Capsulorhexis Using Environmental Scanning Electron Microscopy

PubMed Central

Serrao, Sebastiano; Lombardo, Giuseppe; Desiderio, Giovanni; Buratto, Lucio; Schiano-Lomoriello, Domenico; Pileri, Marco; Lombardo, Marco

2014-01-01

Purpose. To investigate the structure and irregularity of the capsulotomy cutting edges created by two femtosecond (FS) laser platforms in comparison with manual continuous circular capsulorhexis (CCC) using environmental scanning electron microscopy (eSEM). Methods. Ten anterior capsulotomies were obtained using two different FS laser cataract platforms (LenSx, n = 5, and Victus, n = 5). In addition, five manual CCC (n = 5) were obtained using a rhexis forceps. The specimens were imaged by eSEM (FEI Quanta 400, OR, USA). Objective metrics, which included the arithmetic mean deviation of the surface (Sa) and the root-mean-square deviation of the surface (Sq), were used to evaluate the irregularity of both the FS laser capsulotomies and the manual CCC cutting edges. Results. Several microirregularities were shown across the FS laser capsulotomy cutting edges. The edges of manually torn capsules were shown, by comparison of Sa and Sq values, to be smoother (P < 0.05) than the FS laser capsulotomy edges. Conclusions. Work is needed to understand whether the FS laser capsulotomy edge microirregularities, not seen in manual CCC, may act as focal points for the concentration of stress that would increase the risk of capsular tear during phacoemulsification as recently reported in the literature. PMID:25505977

Analysis of femtosecond laser assisted capsulotomy cutting edges and manual capsulorhexis using environmental scanning electron microscopy.

PubMed

Serrao, Sebastiano; Lombardo, Giuseppe; Desiderio, Giovanni; Buratto, Lucio; Schiano-Lomoriello, Domenico; Pileri, Marco; Lombardo, Marco

2014-01-01

Purpose. To investigate the structure and irregularity of the capsulotomy cutting edges created by two femtosecond (FS) laser platforms in comparison with manual continuous circular capsulorhexis (CCC) using environmental scanning electron microscopy (eSEM). Methods. Ten anterior capsulotomies were obtained using two different FS laser cataract platforms (LenSx, n = 5, and Victus, n = 5). In addition, five manual CCC (n = 5) were obtained using a rhexis forceps. The specimens were imaged by eSEM (FEI Quanta 400, OR, USA). Objective metrics, which included the arithmetic mean deviation of the surface (Sa) and the root-mean-square deviation of the surface (Sq), were used to evaluate the irregularity of both the FS laser capsulotomies and the manual CCC cutting edges. Results. Several microirregularities were shown across the FS laser capsulotomy cutting edges. The edges of manually torn capsules were shown, by comparison of Sa and Sq values, to be smoother (P < 0.05) than the FS laser capsulotomy edges. Conclusions. Work is needed to understand whether the FS laser capsulotomy edge microirregularities, not seen in manual CCC, may act as focal points for the concentration of stress that would increase the risk of capsular tear during phacoemulsification as recently reported in the literature.

Activity Enhancement of G-Quadruplex/Hemin DNAzyme by Flanking d(CCC).

PubMed

Chang, Tianjun; Gong, Hongmei; Ding, Pi; Liu, Xiangjun; Li, Weiguo; Bing, Tao; Cao, Zehui; Shangguan, Dihua

2016-03-14

G-quadruplex (G4)/hemin DNAzymes have been extensively applied in bioanalysis and molecular devices. However, their catalytic activity is still much lower than that of proteinous enzymes. The G4/hemin DNAzyme activity is correlated with the G4 conformations and the solution conditions. However, little is known about the effect of the flanking sequences on the activity, though they are important parts of G4s. Here, we report sequences containing d(CCC), flanked on both ends of the G4-core sequences remarkably enhance their DNAzyme activity. By using circular dichroism and UV-visible spectroscopy, the d(CCC) flanking sequences were demonstrated to improve the hemin binding affinity to G4s instead of increasing the parallel G4 formation, which might explain the enhanced DNAzyme activity. Meanwhile, the increased hemin binding ability promoted the degradation of hemin within the DNAzyme by H2O2. Furthermore, the DNAzyme with d(CCC) flanking sequences showed strong tolerance to pH value changes, which makes it more suitable for applications requiring wide pH conditions. The results highlight the influence of the flanking sequences on the DNAzyme activity and provide insightful information for the design of highly active DNAzymes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electron– and positron–molecule scattering: development of the molecular convergent close-coupling method

DOE PAGES

Zammit, Mark C.; Fursa, Dmitry V.; Savage, Jeremy S.; ...

2017-05-22

Starting from first principles, this tutorial describes the development of the adiabatic-nuclei convergent close-coupling (CCC) method and its application to electron and (single-centre) positron scattering from diatomic molecules. In this paper, we give full details of the single-centre expansion CCC method, namely the formulation of the molecular target structure; solving the momentum-space coupled-channel Lippmann-Schwinger equation; deriving adiabatic-nuclei cross sections and calculatingmore » $V$-matrix elements. Selected results are presented for electron and positron scattering from molecular hydrogen H$$_2$$ and electron scattering from the vibrationally excited molecular hydrogen ion H$$_2^+$$ and its isotopologues (D$$_2^+$$, T$$_2^+$$, HD$^+$, HT$^+$ and TD$^+$). Finally, convergence in both the close-coupling (target state) and projectile partial-wave expansions of fixed-nuclei electron- and positron-molecule scattering calculations is demonstrated over a broad energy-range and discussed in detail. In general the CCC results are in good agreement with experiments.« less

Aging of vestibular function evaluated using correlational vestibular autorotation test

PubMed Central

Hsieh, Li-Chun; Lin, Hung-Ching; Lee, Guo-She

2014-01-01

Background Imbalance from degeneration of vestibular end organs is a common problem in the elderly. However, the decline of vestibular function with aging was revealed in few vestibular function tests such as vestibular autorotation test (VAT). In the current VAT, there are drawbacks of poor test–retest reliability, slippage of the sensor at high-speed rotations, and limited data about the effect of aging. We developed a correlational-VAT (cVAT) system that included a small, light sensor (less than 20 g) with wireless data transmission technique to evaluate the aging of vestibular function. Material and methods We enrolled 53 healthy participants aged between 25 and 75 years and divided them into five age groups. The test conditions were vertical and horizontal head autorotations of frequencies from 0 to 3 Hz with closed eyes or open eyes. The cross-correlation coefficient (CCC) between eye velocity and head velocity was obtained for the head autorotations between 1 Hz and 3 Hz. The mean of the CCCs was used to represent the vestibular function. Results Age was significantly and negatively correlated with the mean CCC for all test conditions, including horizontal or vertical autorotations with open eyes or closed eyes (P<0.05). The mean CCC with open eyes declined significantly at 55–65 years old and the mean CCC with closed eyes declined significantly at 65–75 years old. Conclusion Vestibular function evaluated using mean CCC revealed a decline with age, and the function of visual-vestibulo-ocular reflex declined 10 years earlier than the function of vestibulo-ocular reflex. PMID:25214774

High-stability cryogenic scanning tunneling microscope based on a closed-cycle cryostat.

PubMed

Hackley, Jason D; Kislitsyn, Dmitry A; Beaman, Daniel K; Ulrich, Stefan; Nazin, George V

2014-10-01

We report on the design and operation of a cryogenic ultra-high vacuum (UHV) scanning tunneling microscope (STM) coupled to a closed-cycle cryostat (CCC). The STM is thermally linked to the CCC through helium exchange gas confined inside a volume enclosed by highly flexible rubber bellows. The STM is thus mechanically decoupled from the CCC, which results in a significant reduction of the mechanical noise transferred from the CCC to the STM. Noise analysis of the tunneling current shows current fluctuations up to 4% of the total current, which translates into tip-sample distance variations of up to 1.5 picometers. This noise level is sufficiently low for atomic-resolution imaging of a wide variety of surfaces. To demonstrate this, atomic-resolution images of Au(111) and NaCl(100)/Au(111) surfaces, as well as of carbon nanotubes deposited on Au(111), were obtained. Thermal drift analysis showed that under optimized conditions, the lateral stability of the STM scanner can be as low as 0.18 Å/h. Scanning Tunneling Spectroscopy measurements based on the lock-in technique were also carried out, and showed no detectable presence of noise from the closed-cycle cryostat. Using this cooling approach, temperatures as low as 16 K at the STM scanner have been achieved, with the complete cool-down of the system typically taking up to 12 h. These results demonstrate that the constructed CCC-coupled STM is a highly stable instrument capable of highly detailed spectroscopic investigations of materials and surfaces at the atomic scale.

Comparative study on Ti/Zr/V and chromate conversion treated aluminum alloys: Anti-corrosion performance and epoxy coating adhesion properties

NASA Astrophysics Data System (ADS)

Zhu, Wen; Li, Wenfang; Mu, Songlin; Fu, Nianqing; Liao, Zhongmiao

2017-05-01

In this study, a Ti/Zr/V conversion coating (TZVCC) was deposited on the surface of aluminum alloy 6063 (AA6063) as an alternative of the chromate conversion coating (CCC). Both the TZVCC treated AA6063 (TZVCC/AA6063) and CCC treated AA6063 (CCC/AA6063) were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), atomic force microscope (AFM) and contact angle measuring device. The anti-corrosion performance of the TZVCC/AA6063 and CCC/AA6063 was evaluated by electrochemical measurements and neutral salt spray tests. It showed that both the surface roughness and surface free energy of the AA6063 were significantly increased after TZVCC treatment. The anti-corrosion performance of TZVCC/AA6063 was superior to that of CCC/AA6063. In addition, the effects of the TZVCC and CCC on the adhesion properties and anti-corrosion performance of epoxy coating applied on samples were examined by pull-off tests and electrochemical impedance spectroscopy (EIS). The dry, wet and recovery adhesive strengths of the epoxy coating on TZVCC treated samples (epoxy coated TZVCC/AA6063) were very close to those of epoxy coating on CCC treated ones (epoxy coated CCC/AA6063). The epoxy coated TZVCC/AA6063 showed better corrosion resistance than the epoxy coated CCC/AA6063 and epoxy coated AA6063.

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

Zammit, Mark C.; Fursa, Dmitry V.; Savage, Jeremy S.

Starting from first principles, this tutorial describes the development of the adiabatic-nuclei convergent close-coupling (CCC) method and its application to electron and (single-centre) positron scattering from diatomic molecules. In this paper, we give full details of the single-centre expansion CCC method, namely the formulation of the molecular target structure; solving the momentum-space coupled-channel Lippmann-Schwinger equation; deriving adiabatic-nuclei cross sections and calculatingmore » $V$-matrix elements. Selected results are presented for electron and positron scattering from molecular hydrogen H$$_2$$ and electron scattering from the vibrationally excited molecular hydrogen ion H$$_2^+$$ and its isotopologues (D$$_2^+$$, T$$_2^+$$, HD$^+$, HT$^+$ and TD$^+$). Finally, convergence in both the close-coupling (target state) and projectile partial-wave expansions of fixed-nuclei electron- and positron-molecule scattering calculations is demonstrated over a broad energy-range and discussed in detail. In general the CCC results are in good agreement with experiments.« less

Pediatric complex chronic conditions classification system version 2: updated for ICD-10 and complex medical technology dependence and transplantation

PubMed Central

2014-01-01

Background The pediatric complex chronic conditions (CCC) classification system, developed in 2000, requires revision to accommodate the International Classification of Disease 10th Revision (ICD-10). To update the CCC classification system, we incorporated ICD-9 diagnostic codes that had been either omitted or incorrectly specified in the original system, and then translated between ICD-9 and ICD-10 using General Equivalence Mappings (GEMs). We further reviewed all codes in the ICD-9 and ICD-10 systems to include both diagnostic and procedural codes indicative of technology dependence or organ transplantation. We applied the provisional CCC version 2 (v2) system to death certificate information and 2 databases of health utilization, reviewed the resulting CCC classifications, and corrected any misclassifications. Finally, we evaluated performance of the CCC v2 system by assessing: 1) the stability of the system between ICD-9 and ICD-10 codes using data which included both ICD-9 codes and ICD-10 codes; 2) the year-to-year stability before and after ICD-10 implementation; and 3) the proportions of patients classified as having a CCC in both the v1 and v2 systems. Results The CCC v2 classification system consists of diagnostic and procedural codes that incorporate a new neonatal CCC category as well as domains of complexity arising from technology dependence or organ transplantation. CCC v2 demonstrated close comparability between ICD-9 and ICD-10 and did not detect significant discontinuity in temporal trends of death in the United States. Compared to the original system, CCC v2 resulted in a 1.0% absolute (10% relative) increase in the number of patients identified as having a CCC in national hospitalization dataset, and a 0.4% absolute (24% relative) increase in a national emergency department dataset. Conclusions The updated CCC v2 system is comprehensive and multidimensional, and provides a necessary update to accommodate widespread implementation of ICD-10. PMID:25102958

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

Hackley, Jason D.; Kislitsyn, Dmitry A.; Beaman, Daniel K.

We report on the design and operation of a cryogenic ultra-high vacuum (UHV) scanning tunneling microscope (STM) coupled to a closed-cycle cryostat (CCC). The STM is thermally linked to the CCC through helium exchange gas confined inside a volume enclosed by highly flexible rubber bellows. The STM is thus mechanically decoupled from the CCC, which results in a significant reduction of the mechanical noise transferred from the CCC to the STM. Noise analysis of the tunneling current shows current fluctuations up to 4% of the total current, which translates into tip-sample distance variations of up to 1.5 picometers. This noisemore » level is sufficiently low for atomic-resolution imaging of a wide variety of surfaces. To demonstrate this, atomic-resolution images of Au(111) and NaCl(100)/Au(111) surfaces, as well as of carbon nanotubes deposited on Au(111), were obtained. Thermal drift analysis showed that under optimized conditions, the lateral stability of the STM scanner can be as low as 0.18 Å/h. Scanning Tunneling Spectroscopy measurements based on the lock-in technique were also carried out, and showed no detectable presence of noise from the closed-cycle cryostat. Using this cooling approach, temperatures as low as 16 K at the STM scanner have been achieved, with the complete cool-down of the system typically taking up to 12 h. These results demonstrate that the constructed CCC-coupled STM is a highly stable instrument capable of highly detailed spectroscopic investigations of materials and surfaces at the atomic scale.« less

Does flat epithelial atypia have rounder nuclei than columnar cell change/hyperplasia? A morphometric approach to columnar cell lesions of the breast.

PubMed

Yamashita, Yoshiko; Ichihara, Shu; Moritani, Suzuko; Yoon, Han-Seung; Yamaguchi, Masahiro

2016-06-01

Columnar cell lesions of the breast encompass columnar cell change/hyperplasia (CCC/CCH) and flat epithelial atypia (FEA). These have attracted researchers because emerging data suggest that FEA may represent the earliest histologically detectable non-obligate precursor of breast cancer. However, it is occasionally difficult to distinguish FEA from CCC/CCH because of similar histology. Although the nuclei of FEA are frequently described as relatively round compared with those of CCC/CCH, there are few morphometric studies to support this statement. The aim of this study was to provide objective data as to the nuclear shape in columnar cell lesions. As a shape descriptor, we adopted ellipticity that is defined by the formula 2b/2a, where a is the length of the long axis of the ellipse and b is the length of the short axis. Contrary to circularity, ellipticity reflects the overall configuration of an ellipse irrespective of surface irregularity. Our image analysis included generating whole slide images, extracting glandular cell nuclei, measuring nuclear ellipticity, and superimposing graded colors based on execution of results on the captured images. A total of 7917 nuclei extracted from 22 FEA images and 5010 nuclei extracted from 13 CCC/CCH images were analyzed. There was a significant difference in nuclear roundness between FEA and CCC/CCH with mean ellipticity values of 0.723 and 0.679, respectively (p < 0.001, Welch's t test). Furthermore, FEA with malignancy had significantly rounder nuclei than FEA without malignancy (p < 0.001). Our preliminary results suggest that nuclear ellipticity is a key parameter in reproducibly classifying columnar cell lesions of the breast.

Antibiotic resistance of vibrio cholerae: special considerations of R-plasmids.

PubMed

Kuwahara, S

1978-09-01

Studies on the transmission of R plasmid by conjugation between enterobacteria and vibrio or related bacteria were reviewed. The majority of the reports confirmed successful transmission from enterobacteria to Vibrio cholerae and related species, although the transmission frequencies were extremely low and the transmitted R plasmid was very unstable except for thermosensitive kanamycin plasmid and usual R plasmid coexisting with P plasmid. Strains of V. cholerae and Aeromonas liquefaciens as well as A. salmonicida bearing R plasmid were detected in nature. R plasmid was relatively unstable in V. cholerae strains with which transmission of R plasmid to enterobacteria was confirmed. At present, only 3 R plasmids have been obtained from naturally occurring strains of V. cholerae. Although the 2 European plasmids belong to the C incompatibility group with 98 megadalton closed covalent circular DNA molecule, one plasmid belongs to the J group with more than 25 megadalton molecular weight, and no CCC of satelite DNA was detected in bacteria harboring this plasmid.

Optimization of a one-step heat-inducible in vivo mini DNA vector production system.

PubMed

Nafissi, Nafiseh; Sum, Chi Hong; Wettig, Shawn; Slavcev, Roderick A

2014-01-01

While safer than their viral counterparts, conventional circular covalently closed (CCC) plasmid DNA vectors offer a limited safety profile. They often result in the transfer of unwanted prokaryotic sequences, antibiotic resistance genes, and bacterial origins of replication that may lead to unwanted immunostimulatory responses. Furthermore, such vectors may impart the potential for chromosomal integration, thus potentiating oncogenesis. Linear covalently closed (LCC), bacterial sequence free DNA vectors have shown promising clinical improvements in vitro and in vivo. However, the generation of such minivectors has been limited by in vitro enzymatic reactions hindering their downstream application in clinical trials. We previously characterized an in vivo temperature-inducible expression system, governed by the phage λ pL promoter and regulated by the thermolabile λ CI[Ts]857 repressor to produce recombinant protelomerase enzymes in E. coli. In this expression system, induction of recombinant protelomerase was achieved by increasing culture temperature above the 37°C threshold temperature. Overexpression of protelomerase led to enzymatic reactions, acting on genetically engineered multi-target sites called "Super Sequences" that serve to convert conventional CCC plasmid DNA into LCC DNA minivectors. Temperature up-shift, however, can result in intracellular stress responses and may alter plasmid replication rates; both of which may be detrimental to LCC minivector production. We sought to optimize our one-step in vivo DNA minivector production system under various induction schedules in combination with genetic modifications influencing plasmid replication, processing rates, and cellular heat stress responses. We assessed different culture growth techniques, growth media compositions, heat induction scheduling and temperature, induction duration, post-induction temperature, and E. coli genetic background to improve the productivity and scalability of our system, achieving an overall LCC DNA minivector production efficiency of ∼ 90%.We optimized a robust technology conferring rapid, scalable, one-step in vivo production of LCC DNA minivectors with potential application to gene transfer-mediated therapeutics.

Optimization of a One-Step Heat-Inducible In Vivo Mini DNA Vector Production System

PubMed Central

Wettig, Shawn; Slavcev, Roderick A.

2014-01-01

While safer than their viral counterparts, conventional circular covalently closed (CCC) plasmid DNA vectors offer a limited safety profile. They often result in the transfer of unwanted prokaryotic sequences, antibiotic resistance genes, and bacterial origins of replication that may lead to unwanted immunostimulatory responses. Furthermore, such vectors may impart the potential for chromosomal integration, thus potentiating oncogenesis. Linear covalently closed (LCC), bacterial sequence free DNA vectors have shown promising clinical improvements in vitro and in vivo. However, the generation of such minivectors has been limited by in vitro enzymatic reactions hindering their downstream application in clinical trials. We previously characterized an in vivo temperature-inducible expression system, governed by the phage λ pL promoter and regulated by the thermolabile λ CI[Ts]857 repressor to produce recombinant protelomerase enzymes in E. coli. In this expression system, induction of recombinant protelomerase was achieved by increasing culture temperature above the 37°C threshold temperature. Overexpression of protelomerase led to enzymatic reactions, acting on genetically engineered multi-target sites called “Super Sequences” that serve to convert conventional CCC plasmid DNA into LCC DNA minivectors. Temperature up-shift, however, can result in intracellular stress responses and may alter plasmid replication rates; both of which may be detrimental to LCC minivector production. We sought to optimize our one-step in vivo DNA minivector production system under various induction schedules in combination with genetic modifications influencing plasmid replication, processing rates, and cellular heat stress responses. We assessed different culture growth techniques, growth media compositions, heat induction scheduling and temperature, induction duration, post-induction temperature, and E. coli genetic background to improve the productivity and scalability of our system, achieving an overall LCC DNA minivector production efficiency of ∼90%.We optimized a robust technology conferring rapid, scalable, one-step in vivo production of LCC DNA minivectors with potential application to gene transfer-mediated therapeutics. PMID:24586704

Cervi cornus Colla (deer antler glue) induce epidermal differentiation in the reconstruction of skin equivalents.

PubMed

Choi, H-R; Nam, K-M; Kim, D-S; Huh, C-H; Na, J-I; Park, K-C

2013-06-01

In the reconstruction of skin equivalents (SEs), keratinocyte differentiation is important because epidermal differentiation is closely related with barrier function. The aim of this study was to investigate the effects of Cervi cornus Colla (CCC) on the stem cell activity and epidermal differentiation in the reconstruction of skin equivalent. Four different models were constructed according to different composition of dermal substitute. Results showed similar morphologic findings when hyaluronic acid (HA) and/or CCC was added. But, immunohistochemical staining showed that p63 was significantly increased by addition of HA and/or CCC. Increased staining of integrin α6 and β1 was variably observed when HA and/or CCC was added to make dermal substitute. These finding showed that addition of HA and/or CCC may affect the stem cell activity in the reconstruction of skin. Furthermore, filaggrin expression was much increased when CCC was added. It showed that epidermal differentiation was significantly improved by addition of CCC. In conclusion, simultaneous presence of HA and CCC contributed to the stem cell activity and epidermal differentiation in the reconstruction of SE. Legislation in the EU prohibits marketing cosmetics and personal care products that contain constituents that have been examined through animal experiments. To avoid these limitations, SEs can be used for testing the safety or the efficacy of cosmetic ingredients. Therefore, our results showed that combined use of HA and CCC can be helpful for the reconstruction of SE with good stem cell activity and epidermal differentiation. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

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

Ma, Y; Lacroix, F; Lavallee, M

Purpose: To evaluate the commercially released Collapsed Cone convolution-based(CCC) dose calculation module of the Elekta OncentraBrachy(OcB) treatment planning system(TPS). Methods: An allwater phantom was used to perform TG43 benchmarks with single source and seventeen sources, separately. Furthermore, four real-patient heterogeneous geometries (chestwall, lung, breast and prostate) were used. They were selected based on their clinical representativity of a class of clinical anatomies that pose clear challenges. The plans were used as is(no modification). For each case, TG43 and CCC calculations were performed in the OcB TPS, with TG186-recommended materials properly assigned to ROIs. For comparison, Monte Carlo simulation was runmore » for each case with the same material scheme and grid mesh as TPS calculations. Both modes of CCC (standard and high quality) were tested. Results: For the benchmark case, the CCC dose, when divided by that of TG43, yields hot-n-cold spots in a radial pattern. The pattern of the high mode is denser than that of the standard mode and is representative of angular dicretization. The total deviation ((hot-cold)/TG43) is 18% for standard mode and 11% for high mode. Seventeen dwell positions help to reduce “ray-effect”, with the total deviation to 6% (standard) and 5% (high), respectively. For the four patient cases, CCC produces, as expected, more realistic dose distributions than TG43. A close agreement was observed between CCC and MC for all isodose lines, from 20% and up; the 10% isodose line of CCC appears shifted compared to that of MC. The DVH plots show dose deviations of CCC from MC in small volume, high dose regions (>100% isodose). For patient cases, the difference between standard and high modes is almost undiscernable. Conclusion: OncentraBrachy CCC algorithm marks a significant dosimetry improvement relative to TG43 in real-patient cases. Further researches are recommended regarding the clinical implications of the above observations. Support provided by a CIHR grant and CCC system provided by Elekta-Nucletron.« less

Convergent close coupling versus the generalized Sturmian function approach: Wave-function analysis

NASA Astrophysics Data System (ADS)

Ambrosio, M.; Mitnik, D. M.; Gasaneo, G.; Randazzo, J. M.; Kadyrov, A. S.; Fursa, D. V.; Bray, I.

2015-11-01

We compare the physical information contained in the Temkin-Poet (TP) scattering wave function representing electron-impact ionization of hydrogen, calculated by the convergent close-coupling (CCC) and generalized Sturmian function (GSF) methodologies. The idea is to show that the ionization cross section can be extracted from the wave functions themselves. Using two different procedures based on hyperspherical Sturmian functions we show that the transition amplitudes contained in both GSF and CCC scattering functions lead to similar single-differential cross sections. The single-continuum channels were also a subject of the present studies, and we show that the elastic and excitation amplitudes are essentially the same as well.

CCC calculated differential cross sections of electron-H2 scattering

NASA Astrophysics Data System (ADS)

Fursa, Dmitry; Zammit, Mark; Savage, Jeremy; Bray, Igor

2016-09-01

Recently we applied the molecular convergent close-coupling (CCC) method to electron scattering from molecular hydrogen H2. Convergence of the major differential cross sections has been explicitly demonstrated in the fixed-nuclei approximation. A large close-coupling expansion that coupled highly excited states and ionization channels proved to be important to obtain convergent results. Here we present benchmark elastic and electronic excitation differential cross sections for b3Σu+ , a3Σg+ , c3Πu , B1Σu+ , EF1Σg+ , C1Πu , and e3Σu+ states and compare with available experiment and previous calculations. Work supported by Los Alamos National Laboratory and Curtin University.

Inhibition of hepatitis B virus replication via HBV DNA cleavage by Cas9 from Staphylococcus aureus.

PubMed

Liu, Yu; Zhao, Miaoxian; Gong, Mingxing; Xu, Ying; Xie, Cantao; Deng, Haohui; Li, Xueying; Wu, Hongkai; Wang, Zhanhui

2018-04-01

Chronic hepatitis B virus (HBV) infection is difficult to cure due to the presence of covalently closed circular DNA (cccDNA). Accumulating evidence indicates that the CRISPR/Cas9 system effectively disrupts HBV genome, including cccDNA, in vitro and in vivo. However, efficient delivery of CRISPR/Cas9 system to the liver or hepatocytes using an adeno-associated virus (AAV) vector remains challenging due to the large size of Cas9 from Streptococcus pyogenes (Sp). The recently identified Cas9 protein from Staphylococcus aureus (Sa) is smaller than SpCas9 and thus is able to be packaged into the AAV vector. To examine the efficacy of SaCas9 system on HBV genome destruction, we designed 5 guide RNAs (gRNAs) that targeted different HBV genotypes, 3 of which were shown to be effective. The SaCas9 system significantly reduced HBV antigen expression, as well as pgRNA and cccDNA levels, in Huh7, HepG2.2.15 and HepAD38 cells. The dual expression of gRNAs/SaCas9 in these cell lines resulted in more efficient HBV genome cleavage. In the mouse model, hydrodynamic injection of gRNA/SaCas9 plasmids resulted in significantly lower levels of HBV protein expression. We also delivered the SaCas9 system into mice with persistent HBV replication using an AAV vector. Both the AAV vector and the mRNA of Cas9 could be detected in the C3H mouse liver cells. Decreased hepatitis B surface antigen (HBsAg), HBV DNA and pgRNA levels were observed when a higher titer of AAV was injected, although this decrease was not significantly different from the control. In summary, the SaCas9 system accurately and efficiently targeted the HBV genome and inhibited HBV replication both in vitro and in vivo. The system was delivered by an AAV vector and maybe used as a novel therapeutic strategy against chronic HBV infection. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of dendritic cells from hepatitis B virus transgenic mice-stimulated autologous lymphocytes on hepatitis B virus replication: a study on the impact of specific sensitized effector cells on in vitro virus replication.

PubMed

Shen, Zhong-Yang; Zheng, Wei-Ping; Liu, Tao; Yang, Yang; Song, Hong-Li

2015-03-01

The objective of this study was to explore the effects of dendritic cells (DCs) from hepatitis B virus (HBV) transgenic mice-stimulated autologous lymphocytes on in vitro HBV replication. DCs from HBV transgenic mice were induced to maturity by lipopolysaccharide, followed by incubation with hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in vitro. Mature DCs and autologous lymphocytes were co-stimulated to form specific sensitized immune effector cells (IEC), which were then co-cultured with the human hepatoma cell line HepG2.2.15. Changes in morphology and activity of hepatocytes were then observed, as well as analysis of changes in liver enzyme, and HBV DNA and inflammatory cytokine levels in the culture supernatant. Intracellular HBV DNA and covalently closed circular DNA (cccDNA) concentration were measured by real-time polymerase chain reaction. Co-stimulation by mature DCs and IEC showed no impact on the morphology and liver enzyme expression level of HepG2.2.15 cells, but the supernatant HBV DNA and intracellular HBV DNA and cccDNA levels decreased significantly compared with those cells co-cultured with immature DCs. Secretion of inflammatory cytokines in the supernatant showed that when HBV DNA was highly expressed, the concentration of IFN-γ and IL-2 decreased, while IL-10 increased. Contrastingly, when HBV DNA had low expression, the concentration of IFN-γ and IL-2 increased and IL-10 decreased. Co-stimulation of HBV-related antigen-induced mature DCs and autologous lymphocytes showed inhibitory effects on ex vivo HBV replication, and cytokines were suggested to mediate this effect.

Progress and Prospects of Anti-HBV Gene Therapy Development

PubMed Central

Maepa, Mohube B.; Roelofse, Ilke; Ely, Abdullah; Arbuthnot, Patrick

2015-01-01

Despite the availability of an effective vaccine against hepatitis B virus (HBV), chronic infection with the virus remains a major global health concern. Current drugs against HBV infection are limited by emergence of resistance and rarely achieve complete viral clearance. This has prompted vigorous research on developing better drugs against chronic HBV infection. Advances in understanding the life cycle of HBV and improvements in gene-disabling technologies have been impressive. This has led to development of better HBV infection models and discovery of new drug candidates. Ideally, a regimen against chronic HBV infection should completely eliminate all viral replicative intermediates, especially covalently closed circular DNA (cccDNA). For the past few decades, nucleic acid-based therapy has emerged as an attractive alternative that may result in complete clearance of HBV in infected patients. Several genetic anti-HBV strategies have been developed. The most studied approaches include the use of antisense oligonucleotides, ribozymes, RNA interference effectors and gene editing tools. This review will summarize recent developments and progress made in the use of gene therapy against HBV. PMID:26263978

DNA damage by various radiations

NASA Astrophysics Data System (ADS)

Hasegawa, K.; Yoshioka, H.; Yoshioka, H.

1997-01-01

In an attempt to shed light on the influence of tritiated water on DNA we have investigated the post-irradiation damage with a simple plasmid DNA, pBR322 and pUC18. The survival of covalently closed circular (CCC) DNA form was directly followed by agarose gel electrophoresis. The survival percentage of DNA in tritiated water was almost the same as with the irradiation with X-rays at the same absorbed dose. For irradiation with γ-rays, on the other hand, the decay rate was larger than those observed with both tritiated water and X-rays. The percentages of breakage for DNA in tritiated water, X-rays and γ-rays were found to be 34, 38 and 33% at 100 Gy of absorbed dose. The effect of dose rate was not observed for irradiation with tritiated water, X-rays and γ-rays. In order to study protection of DNA against radiation, we investigated the protecting effect of tea catechin which is the main component of (-)-epigallocatechin gallate (EGCg). The protection mechanism for DNA against radiation-induced scission has been studied using ESR spin-trapping method.

Primary clear cell carcinoma of parotid gland: Case report and review of literature.

PubMed

Rodríguez, Marta Saldaña; Reija, Maria Fe García; Rodilla, Irene González

2013-01-01

Clear cell carcinoma (CCC) is a rare low-grade carcinoma that represents only 1% to 2% of all salivary glands tumors. The finding of a clear cell tumor in a parotid gland involves the necessity of differential diagnosis between primary clear cell parotid tumors and metastases, mainly from kidney. The biological behavior is not very aggressive and development, which is very slow, is usually asymptomatic and indeed, the tumor often reaches considerable dimensions before being diagnosed. The treatment of choice is the surgical excision. There are rare cases of local recurrence and distant metastases. The aim of this article is to report a primary CCC in the parotid gland that microscopically closely resembled a metastatic CCC of renal origin, making microscopic differentiation difficult.

Primary clear cell carcinoma of parotid gland: Case report and review of literature

PubMed Central

Rodríguez, Marta Saldaña; Reija, Maria Fe García; Rodilla, Irene González

2013-01-01

Clear cell carcinoma (CCC) is a rare low-grade carcinoma that represents only 1% to 2% of all salivary glands tumors. The finding of a clear cell tumor in a parotid gland involves the necessity of differential diagnosis between primary clear cell parotid tumors and metastases, mainly from kidney. The biological behavior is not very aggressive and development, which is very slow, is usually asymptomatic and indeed, the tumor often reaches considerable dimensions before being diagnosed. The treatment of choice is the surgical excision. There are rare cases of local recurrence and distant metastases. The aim of this article is to report a primary CCC in the parotid gland that microscopically closely resembled a metastatic CCC of renal origin, making microscopic differentiation difficult. PMID:23798840

Assessing assay agreement estimation for multiple left-censored data: a multiple imputation approach.

PubMed

Lapidus, Nathanael; Chevret, Sylvie; Resche-Rigon, Matthieu

2014-12-30

Agreement between two assays is usually based on the concordance correlation coefficient (CCC), estimated from the means, standard deviations, and correlation coefficient of these assays. However, such data will often suffer from left-censoring because of lower limits of detection of these assays. To handle such data, we propose to extend a multiple imputation approach by chained equations (MICE) developed in a close setting of one left-censored assay. The performance of this two-step approach is compared with that of a previously published maximum likelihood estimation through a simulation study. Results show close estimates of the CCC by both methods, although the coverage is improved by our MICE proposal. An application to cytomegalovirus quantification data is provided. Copyright © 2014 John Wiley & Sons, Ltd.

Clinical applications of correlational vestibular autorotation test.

PubMed

Hsieh, Li-Chun; Lin, Te-Ming; Chang, Yu-Min; Kuo, Terry B J; Lee, Gho-She

2015-06-01

The correlational vestibular autorotation test (VAT) system has the advantages of good test-retest reliability and calibrations of absolute degrees of eye movement are unnecessary when acquiring a cross correlation coefficient (CCC). The approach is able to efficiently detect peripheral vestibulopathies. A VAT has some drawbacks including poor test-retest reliability and slippage of sensor. This study aimed to develop a correlational VAT system and to evaluate the reliability and applicability of this system. Twenty healthy participants and 10 vertiginous patients were enrolled. Vertical and horizontal autorotations from 0 to 3 Hz with either closed or open eyes were performed. A small sensor and a wireless transmission technique were used to acquire the electro-ocular graph and head velocity signals. The two signals were analyzed using CCCs to assess the functioning of the vestibular ocular reflex (VOR). The results showed a significantly greater CCC for open-eye versus closed-eye of head autorotations. The CCCs also increased significantly with head rotational frequencies. Moreover, the CCCs significantly correlated with the VOR gains at autorotation frequencies ≥1.0 Hz. The test-retest reliability was good (intraclass correlation coefficients ≥0.85). The vertiginous participants had significantly lower individual CCCs and overall average CCC than age- and-gender matched controls.

9 Closed chest compressions reduce survival in a model of haemorrhage-induced traumatic cardiac arrest.

PubMed

Watts, Sarah; Smith, Jason; Gwyther, Robert; Kirkman, Emrys

2017-12-01

Closed chest compressions (CCC) are a key component of resuscitation from medical causes of cardiac arrest, but when haemorrhage, the leading cause of preventable battlefield deaths, is the likely cause there is little evidence to support their use. Resuscitation protocols for traumatic cardiac arrest (TCA) highlight the importance of addressing reversible causes, such as the administration of fluids to treat hypovolaemia. This study evaluated whether CCC were beneficial following haemorrhage-induced TCA and additionally whether resuscitation with blood improved physiological outcomes. The study was conducted with the authority of UK Animals (Scientific Procedures) Act 1986 using 39 terminally anesthetised Large White pigs (35 kg, 29-40 kg) instrumented for invasive physiological monitoring. Following instrumentation and baseline measurements, animals underwent tissue injury (captive bolt to the right thigh) and controlled haemorrhage (30% blood volume). Mean arterial blood pressure (MAP) was maintained at 45 mmHg for 60 min, followed by a further controlled haemorrhage to a MAP of 20 mmHg. As arterial blood and pulse pressures spontaneously deteriorated further over a 5 min period, the randomised resuscitation protocol was initiated as follows: CCC (n=6); IV 0.9% saline (Sal n=8); IV autologous whole blood (WB n=8); IV saline +chest compressions (Sal +CCC n=9); and IV whole blood +chest compressions (WB +CCC n=8). 3×10 ml/kg fluid boluses were administered using the Belmont Rapid Infuser (200 ml/min). CCC were performed using the LUCAS II Chest Compression System.Outcome was attainment of return of spontaneous circulation (ROSC) 15 min post-resuscitation. ROSC was categorised by MAP (MAP ≥50 mmHg=ROSC; MAP >20 <50 mmHg=partial ROSC; MAP ≤20 mmHg=dead).emermed;34/12/A866-a/F1F1F1Figure 1 RESULTS: Outcome was significantly worse in the group that received CCC compared to WB and Sal groups (6/6 dead versus 0/8 and 0/8 respectively) (p<0.0001).A significantly higher number of animals attained ROSC in WB compared to Sal group (6/8 versus 0/8 ROSC and 2/8 versus 8/8 partial ROSC respectively) (p=0.0069).There were some none significant differences between WB and WB+CCC groups (6/8 versus 5/8 ROSC, 2/8 versus 1/8 partial ROSC and 0/8 versus 2/8 dead respectively) (p=0.4411).No animals attained ROSC in the Sal and Sal+CCC groups however significantly more animals died in the Sal+CCC group (0/8 versus 0/9 ROSC, 8/8 versus 2/9 partial ROSC and 0/8 versus 7/9 dead respectively) (p=0.0023). CCC were associated with increased mortality compared to intravenous fluid resuscitation. Resuscitation with whole blood demonstrated the greatest physiological benefit as demonstrated by highest numbers of animals achieving ROSC. © 2017, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Myocardial Chemokine Expression and Intensity of Myocarditis in Chagas Cardiomyopathy Are Controlled by Polymorphisms in CXCL9 and CXCL10

PubMed Central

Nogueira, Luciana Gabriel; Santos, Ronaldo Honorato Barros; Ianni, Barbara Maria; Fiorelli, Alfredo Inácio; Mairena, Eliane Conti; Benvenuti, Luiz Alberto; Frade, Amanda; Donadi, Eduardo; Dias, Fabrício; Saba, Bruno; Wang, Hui-Tzu Lin; Fragata, Abilio; Sampaio, Marcelo; Hirata, Mario Hiroyuki; Buck, Paula; Mady, Charles; Bocchi, Edimar Alcides; Stolf, Noedir Antonio; Kalil, Jorge; Cunha-Neto, Edecio

2012-01-01

Background Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. Methods and Results Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2–6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. Conclusions Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that CXCL9 and CXCL10 are master regulators of myocardial inflammatory cell migration, perhaps affecting clinical progression to the life-threatening form of CCC. PMID:23150742

CCC calculated integrated cross sections of electron-H2 scattering

NASA Astrophysics Data System (ADS)

Zammit, Mark; Fursa, Dmitry; Savage, Jeremy; Bray, Igor

2016-09-01

Recently we applied the molecular convergent close-coupling (CCC) method to electron scattering from molecular hydrogen H2. Convergence of the major integrated cross sections has been explicitly demonstrated in the fixed-nuclei approximation by increasing the number of H2 target states in the close-coupling expansion from 9 to 491. The calculations have been performed using a projectile partial wave expansion with maximum orbital angular momentum Lmax = 8 and total orbital angular momentum projections | M | <= 8 . Coupling to the ionization continuum is modeled via a large pseudo state expansion, which we found is required to obtain reliable elastic and excitation cross sections. Here we present benchmark elastic, single-ionization, electronic excitation and total integrated cross sections over a broad energy range (0.1 to 300 eV) and compare with available experiment and previous calculations. Los Alamos National Laboratory and Curtin University.

Vibrational excitation and vibrationally resolved electronic excitation cross sections of positron-H2 scattering

NASA Astrophysics Data System (ADS)

Zammit, Mark; Fursa, Dmitry; Savage, Jeremy; Bray, Igor

2016-09-01

Vibrational excitation and vibrationally resolved electronic excitation cross sections of positron-H2 scattering have been calculated using the single-centre molecular convergent close-coupling (CCC) method. The adiabatic-nuclei approximation was utilized to model the above scattering processes and obtain the vibrationally resolved positron-H2 scattering length. As previously demonstrated, the CCC results are converged and accurately account for virtual and physical positronium formation by coupling basis functions with large orbital angular momentum. Here vibrationally resolved integrated and differential cross sections are presented over a wide energy range and compared with previous calculations and available experiments. Los Alamos National Laboratory and Curtin University.

Simple equations to simulate closed-loop recycling liquid-liquid chromatography: Ideal and non-ideal recycling models.

PubMed

Kostanyan, Artak E

2015-12-04

The ideal (the column outlet is directly connected to the column inlet) and non-ideal (includes the effects of extra-column dispersion) recycling equilibrium-cell models are used to simulate closed-loop recycling counter-current chromatography (CLR CCC). Simple chromatogram equations for the individual cycles and equations describing the transport and broadening of single peaks and complex chromatograms inside the recycling closed-loop column for ideal and non-ideal recycling models are presented. The extra-column dispersion is included in the theoretical analysis, by replacing the recycling system (connecting lines, pump and valving) by a cascade of Nec perfectly mixed cells. To evaluate extra-column contribution to band broadening, two limiting regimes of recycling are analyzed: plug-flow, Nec→∞, and maximum extra-column dispersion, Nec=1. Comparative analysis of ideal and non-ideal models has shown that when the volume of the recycling system is less than one percent of the column volume, the influence of the extra-column processes on the CLR CCC separation may be neglected. Copyright © 2015 Elsevier B.V. All rights reserved.

Therapeutic Antiviral Effect of the Nucleic Acid Polymer REP 2055 against Persistent Duck Hepatitis B Virus Infection

PubMed Central

Noordeen, Faseeha; Scougall, Catherine A.; Grosse, Arend; Qiao, Qiao; Ajilian, Behzad B.; Reaiche-Miller, Georget; Finnie, John; Werner, Melanie; Broering, Ruth; Schlaak, Joerg F.; Vaillant, Andrew; Jilbert, Allison R.

2015-01-01

Previous studies have demonstrated that nucleic acid polymers (NAPs) have both entry and post-entry inhibitory activity against duck hepatitis B virus (DHBV) infection. The inhibitory activity exhibited by NAPs prevented DHBV infection of primary duck hepatocytes in vitro and protected ducks from DHBV infection in vivo and did not result from direct activation of the immune response. In the current study treatment of primary human hepatocytes with NAP REP 2055 did not induce expression of the TNF, IL6, IL10, IFNA4 or IFNB1 genes, confirming the lack of direct immunostimulation by REP 2055. Ducks with persistent DHBV infection were treated with NAP 2055 to determine if the post-entry inhibitory activity exhibited by NAPs could provide a therapeutic effect against established DHBV infection in vivo. In all REP 2055-treated ducks, 28 days of treatment lead to initial rapid reductions in serum DHBsAg and DHBV DNA and increases in anti-DHBs antibodies. After treatment, 6/11 ducks experienced a sustained virologic response: DHBsAg and DHBV DNA remained at low or undetectable levels in the serum and no DHBsAg or DHBV core antigen positive hepatocytes and only trace amounts of DHBV total and covalently closed circular DNA (cccDNA) were detected in the liver at 9 or 16 weeks of follow-up. In the remaining 5/11 REP 2055-treated ducks, all markers of DHBV infection rapidly rebounded after treatment withdrawal: At 9 and 16 weeks of follow-up, levels of DHBsAg and DHBcAg and DHBV total and cccDNA in the liver had rebounded and matched levels observed in the control ducks treated with normal saline which remained persistently infected with DHBV. These data demonstrate that treatment with the NAP REP 2055 can lead to sustained control of persistent DHBV infection. These effects may be related to the unique ability of REP 2055 to block release of DHBsAg from infected hepatocytes. PMID:26560490

VizieR Online Data Catalog: Inelastic e+Mg collision data (Barklem+, 2017)

NASA Astrophysics Data System (ADS)

Barklem, P. S.; Osorio, Y.; Fursa, D. V.; Bray, I.; Zatsarinny, O.; Bartschat, K.; Jerkstrand, A.

2017-06-01

The file states.dat lists the considered states. The remaining files then provide the effective collision strength matrices for various temperatures from the convergent close coupling (CCC) and B-spline R-matrix (BSR) calculations. (27 data files).

Construction and Characterization of an in-vivo Linear Covalently Closed DNA Vector Production System

PubMed Central

2012-01-01

Background While safer than their viral counterparts, conventional non-viral gene delivery DNA vectors offer a limited safety profile. They often result in the delivery of unwanted prokaryotic sequences, antibiotic resistance genes, and the bacterial origins of replication to the target, which may lead to the stimulation of unwanted immunological responses due to their chimeric DNA composition. Such vectors may also impart the potential for chromosomal integration, thus potentiating oncogenesis. We sought to engineer an in vivo system for the quick and simple production of safer DNA vector alternatives that were devoid of non-transgene bacterial sequences and would lethally disrupt the host chromosome in the event of an unwanted vector integration event. Results We constructed a parent eukaryotic expression vector possessing a specialized manufactured multi-target site called “Super Sequence”, and engineered E. coli cells (R-cell) that conditionally produce phage-derived recombinase Tel (PY54), TelN (N15), or Cre (P1). Passage of the parent plasmid vector through R-cells under optimized conditions, resulted in rapid, efficient, and one step in vivo generation of mini lcc—linear covalently closed (Tel/TelN-cell), or mini ccc—circular covalently closed (Cre-cell), DNA constructs, separated from the backbone plasmid DNA. Site-specific integration of lcc plasmids into the host chromosome resulted in chromosomal disruption and 105 fold lower viability than that seen with the ccc counterpart. Conclusion We offer a high efficiency mini DNA vector production system that confers simple, rapid and scalable in vivo production of mini lcc DNA vectors that possess all the benefits of “minicircle” DNA vectors and virtually eliminate the potential for undesirable vector integration events. PMID:23216697

The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans

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

Goyal, Ashish; Ribeiro, Ruy Miguel; Perelson, Alan S.

Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it has been hypothesized that proliferation of infected cells resulting in uninfected progeny and/or cytokine-mediated degradation of covalently closed circular DNA (cccDNA) leading to the cure of infected cells are two major mechanisms assisting the adaptive immune response in the clearance of acute HBV infection in humans. We employed fitting of mathematical models to human acute infection datamore » together with physiological constraints to investigate the role of these hypothesized mechanisms in the clearance of infection. Results suggest that cellular proliferation of infected cells resulting in two uninfected cells is required to minimize the destruction of the liver during the clearance of acute HBV infection. In contrast, we find that a cytokine-mediated cure of infected cells alone is insufficient to clear acute HBV infection. Lastly, our modeling indicates that HBV clearance without lethal loss of liver mass is associated with the production of two uninfected cells upon proliferation of an infected cell.« less

The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans

DOE PAGES

Goyal, Ashish; Ribeiro, Ruy Miguel; Perelson, Alan S.

2017-11-18

Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it has been hypothesized that proliferation of infected cells resulting in uninfected progeny and/or cytokine-mediated degradation of covalently closed circular DNA (cccDNA) leading to the cure of infected cells are two major mechanisms assisting the adaptive immune response in the clearance of acute HBV infection in humans. We employed fitting of mathematical models to human acute infection datamore » together with physiological constraints to investigate the role of these hypothesized mechanisms in the clearance of infection. Results suggest that cellular proliferation of infected cells resulting in two uninfected cells is required to minimize the destruction of the liver during the clearance of acute HBV infection. In contrast, we find that a cytokine-mediated cure of infected cells alone is insufficient to clear acute HBV infection. Lastly, our modeling indicates that HBV clearance without lethal loss of liver mass is associated with the production of two uninfected cells upon proliferation of an infected cell.« less

Activating the innate immune response to counter chronic hepatitis B virus infection.

PubMed

Lamb, Camilla; Arbuthnot, Patrick

2016-12-01

Chronic infection with hepatitis B virus (HBV) is endemic to several populous parts of the world, where resulting complicating cirrhosis and hepatocellular carcinoma occur commonly. Licensed drugs to treat the infection have limited curative efficacy, and development of therapies that eliminate all replication intermediates of HBV is a priority. Areas covered: The recent demonstration that the activation of the innate immune response may eradicate HBV from infected hepatocytes has a promising therapeutic application. Small molecule stimulators of Toll-like receptors (TLRs) inhibit replication of woodchuck hepatitis virus in woodchucks and HBV in chimpanzees and mice. Early stage clinical trials using GS-9620, a TLR7 agonist, indicate that this candidate antiviral is well tolerated in humans. Using an alternative approach, triggering the innate immune response with agonists of lymphotoxin-β receptor caused efficient APOBEC-mediated deamination and degradation of viral covalently closed circular DNA. Expert opinion: Eliminating HBV cccDNA from infected individuals would constitute a cure, and has become the focus of intensive research that employs various therapeutic approaches, including gene therapy. Immunomodulation through innate immune activation shows promise for the treatment of chronic infection of HBV (CHB) and, used in combination with other therapeutics, may contribute to the global control of infections and ultimately to the eradication of HBV.

40 CFR Table 1 to Subpart Ccc of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart CCC

Code of Federal Regulations, 2014 CFR

2014-07-01

... (40 CFR Part 63, Subpart A) to Subpart CCC 1 Table 1 to Subpart CCC of Part 63 Protection of... Pt. 63, Subpt. CCC, Table 1 Table 1 to Subpart CCC of Part 63—Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart CCC Reference Applies to Subpart CCC Explanation 63.1-63.5 Yes. 63...

40 CFR Table 1 to Subpart Ccc of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart CCC

Code of Federal Regulations, 2013 CFR

2013-07-01

... (40 CFR Part 63, Subpart A) to Subpart CCC 1 Table 1 to Subpart CCC of Part 63 Protection of... Pt. 63, Subpt. CCC, Table 1 Table 1 to Subpart CCC of Part 63—Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart CCC Reference Applies to Subpart CCC Explanation 63.1-63.5 Yes. 63...

40 CFR Table 1 to Subpart Ccc of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart CCC

Code of Federal Regulations, 2011 CFR

2011-07-01

... (40 CFR Part 63, Subpart A) to Subpart CCC 1 Table 1 to Subpart CCC of Part 63 Protection of... Pt. 63, Subpt. CCC, Table 1 Table 1 to Subpart CCC of Part 63—Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart CCC Reference Applies to Subpart CCC Explanation 63.1-63.5 Yes. 63...

40 CFR Table 1 to Subpart Ccc of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart CCC

Code of Federal Regulations, 2010 CFR

2010-07-01

... (40 CFR Part 63, Subpart A) to Subpart CCC 1 Table 1 to Subpart CCC of Part 63 Protection of... Pt. 63, Subpt. CCC, Table 1 Table 1 to Subpart CCC of Part 63—Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart CCC Reference Applies to Subpart CCC Explanation 63.1-63.5 Yes. 63...

40 CFR Table 1 to Subpart Ccc of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart CCC

Code of Federal Regulations, 2012 CFR

2012-07-01

... (40 CFR Part 63, Subpart A) to Subpart CCC 1 Table 1 to Subpart CCC of Part 63 Protection of... Pt. 63, Subpt. CCC, Table 1 Table 1 to Subpart CCC of Part 63—Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart CCC Reference Applies to Subpart CCC Explanation 63.1-63.5 Yes. 63...

Diet quality of supermarket sales circulars measured by the Healthy Eating Index-2010

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to determine how closely the contents of weekly supermarket sales circulars conform to current dietary guidance and how closely the diet quality of those foods compare to that of the U.S. population’s intakes. Food and beverage items (n = 9,151) in 52 weekly circulars ...

7 CFR 1493.70 - Guarantee rates and fees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... risk that CCC assumes, as determined by CCC, and any other factors which CCC determines appropriate for...

7 CFR 1493.70 - Guarantee rates and fees.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... risk that CCC assumes, as determined by CCC, and any other factors which CCC determines appropriate for...

7 CFR 1493.320 - Recovery of losses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... of loss to the exporter or the exporter's assignee, CCC will notify the foreign bank of CCC's rights... to the Treasurer, CCC. If such monies are not received by CCC within 15 days from the date of...

7 CFR 1404.7 - Misrepresentations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE GENERAL REGULATIONS AND POLICIES ASSIGNMENT OF PAYMENTS § 1404.7 Misrepresentations. If FSA or CCC... executing Forms CCC-36, CCC-251 or CCC-252, FSA or CCC shall give notice thereof to the assignor and the assignee. If, after investigation and opportunity for the assignor and assignee to be heard, FSA or CCC...

7 CFR 1404.7 - Misrepresentations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURE GENERAL REGULATIONS AND POLICIES ASSIGNMENT OF PAYMENTS § 1404.7 Misrepresentations. If FSA or CCC... executing Forms CCC-36, CCC-251 or CCC-252, FSA or CCC shall give notice thereof to the assignor and the assignee. If, after investigation and opportunity for the assignor and assignee to be heard, FSA or CCC...

7 CFR 1493.520 - Recovery of losses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... of loss to the exporter or the exporter's assignee, CCC will notify the importer of CCC's rights..., CCC. If such monies are not received by CCC within 15 business days from the date of recovery by the...

7 CFR 1493.320 - Recovery of losses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... of loss to the exporter or the exporter's assignee, CCC will notify the foreign bank of CCC's rights... to the Treasurer, CCC. If such monies are not received by CCC within 15 days from the date of...

7 CFR 1404.7 - Misrepresentations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGRICULTURE GENERAL REGULATIONS AND POLICIES ASSIGNMENT OF PAYMENTS § 1404.7 Misrepresentations. If FSA or CCC... executing Forms CCC-36, CCC-251 or CCC-252, FSA or CCC shall give notice thereof to the assignor and the assignee. If, after investigation and opportunity for the assignor and assignee to be heard, FSA or CCC...

7 CFR 1404.7 - Misrepresentations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE GENERAL REGULATIONS AND POLICIES ASSIGNMENT OF PAYMENTS § 1404.7 Misrepresentations. If FSA or CCC... executing Forms CCC-36, CCC-251 or CCC-252, FSA or CCC shall give notice thereof to the assignor and the assignee. If, after investigation and opportunity for the assignor and assignee to be heard, FSA or CCC...

7 CFR 1493.520 - Recovery of losses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... of loss to the exporter or the exporter's assignee, CCC will notify the importer of CCC's rights..., CCC. If such monies are not received by CCC within 15 business days from the date of recovery by the...

7 CFR 1404.7 - Misrepresentations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURE GENERAL REGULATIONS AND POLICIES ASSIGNMENT OF PAYMENTS § 1404.7 Misrepresentations. If FSA or CCC... executing Forms CCC-36, CCC-251 or CCC-252, FSA or CCC shall give notice thereof to the assignor and the assignee. If, after investigation and opportunity for the assignor and assignee to be heard, FSA or CCC...

7 CFR 1493.200 - General statement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... Commodity Credit Corporation's (CCC) Facility Guarantee Program (FGP). CCC will issue facility payment... payment guarantee issued by CCC. ...

7 CFR 1493.200 - General statement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... Commodity Credit Corporation's (CCC) Facility Guarantee Program (FGP). CCC will issue facility payment... payment guarantee issued by CCC. ...

7 CFR 1494.601 - Acceptance of offers by CCC.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Acceptance of offers by CCC. 1494.601 Section 1494....601 Acceptance of offers by CCC. (a) Establishment of acceptable sales prices and CCC bonuses. For each Invitation, CCC will establish sales prices for the eligible commodity and CCC bonus amounts which...

7 CFR 1494.601 - Acceptance of offers by CCC.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Acceptance of offers by CCC. 1494.601 Section 1494....601 Acceptance of offers by CCC. (a) Establishment of acceptable sales prices and CCC bonuses. For each Invitation, CCC will establish sales prices for the eligible commodity and CCC bonus amounts which...

7 CFR 1494.601 - Acceptance of offers by CCC.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Acceptance of offers by CCC. 1494.601 Section 1494....601 Acceptance of offers by CCC. (a) Establishment of acceptable sales prices and CCC bonuses. For each Invitation, CCC will establish sales prices for the eligible commodity and CCC bonus amounts which...

The metabolite products of chlorocholine chloride (CCC) in eggs and meat of laying hens fed 15N-CCC containing diets.

PubMed

Chakeredza, S; Edrada, R A; Ebel, R; ter Meulen, U

2006-04-01

An experiment was conducted to evaluate the metabolic products of chlorocholine chloride (CCC) in eggs and meat of laying hens fed a diet containing (15)N-CCC. Ten brown laying hens were randomly divided into two groups of five each. One group was offered (15)N-CCC free diet while the other group received a diet with 100 ppm (15)N-CCC for 11 days. Samples of eggs and meat from the laying hens were collected. Egg yolks and albumen were separated. Meat was collected from the breast and femur. The metabolic products of CCC were measured using ion trap electrospray ionisation mass spectrometry (ion trap-ESI-MS/MS). Determination of CCC or its metabolites in eggs and meat showed that CCC was metabolised to choline. Corresponding MS/MS spectra were obtained for m/z 104 (choline) or 105 ((15)N-choline), whereas nothing was detected at m/z 122 (CCC) or 123 ((15)N-CCC). The results from this study indicate that CCC will be metabolised in tissues of laying hens.

7 CFR 1404.4 - Execution of assignment form.

Code of Federal Regulations, 2013 CFR

2013-01-01

... assignment form. (a)(1) The assignment of any FSA or CCC payment must be made by the execution of Form CCC-36 or Forms CCC-251 and CCC-252. Form CCC-36 is applicable to payments made under programs administered... applicable to any other program which is administered by a county ASC committee. Forms CCC-251 and 252 are...

7 CFR 1404.4 - Execution of assignment form.

Code of Federal Regulations, 2011 CFR

2011-01-01

... assignment form. (a)(1) The assignment of any FSA or CCC payment must be made by the execution of Form CCC-36 or Forms CCC-251 and CCC-252. Form CCC-36 is applicable to payments made under programs administered... applicable to any other program which is administered by a county ASC committee. Forms CCC-251 and 252 are...

7 CFR 1404.4 - Execution of assignment form.

Code of Federal Regulations, 2014 CFR

2014-01-01

... assignment form. (a)(1) The assignment of any FSA or CCC payment must be made by the execution of Form CCC-36 or Forms CCC-251 and CCC-252. Form CCC-36 is applicable to payments made under programs administered... applicable to any other program which is administered by a county ASC committee. Forms CCC-251 and 252 are...

7 CFR 1404.4 - Execution of assignment form.

Code of Federal Regulations, 2010 CFR

2010-01-01

... assignment form. (a)(1) The assignment of any FSA or CCC payment must be made by the execution of Form CCC-36 or Forms CCC-251 and CCC-252. Form CCC-36 is applicable to payments made under programs administered... applicable to any other program which is administered by a county ASC committee. Forms CCC-251 and 252 are...

7 CFR 1404.4 - Execution of assignment form.

Code of Federal Regulations, 2012 CFR

2012-01-01

... assignment form. (a)(1) The assignment of any FSA or CCC payment must be made by the execution of Form CCC-36 or Forms CCC-251 and CCC-252. Form CCC-36 is applicable to payments made under programs administered... applicable to any other program which is administered by a county ASC committee. Forms CCC-251 and 252 are...

7 CFR 1493.200 - General statement.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... (CCC) Facility Guarantee Program (FGP). CCC will issue facility payment guarantees for project... so, will be incorporated by reference on the face of the facility payment guarantee issued by CCC. ...

7 CFR 1493.200 - General statement.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... (CCC) Facility Guarantee Program (FGP). CCC will issue facility payment guarantees for project... so, will be incorporated by reference on the face of the facility payment guarantee issued by CCC. ...

7 CFR 1493.200 - General statement.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... (CCC) Facility Guarantee Program (FGP). CCC will issue facility payment guarantees for project... so, will be incorporated by reference on the face of the facility payment guarantee issued by CCC. ...

7 CFR 1493.130 - Recovery of losses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... exporter's assignee, CCC will notify the foreign bank of CCC's rights under the subrogation agreement to...

7 CFR 1493.60 - Payment guarantee.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.60 Payment guarantee. (a) CCC's obligation. The payment guarantee will provide that CCC agrees to pay the...

7 CFR 1493.60 - Payment guarantee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.60 Payment guarantee. (a) CCC's obligation. The payment guarantee will provide that CCC...

7 CFR 1493.130 - Recovery of losses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... exporter's assignee, CCC will notify the foreign bank of CCC's rights under the subrogation agreement to...

7 CFR 1493.60 - Payment guarantee.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.60 Payment guarantee. (a) CCC's obligation. The payment guarantee will provide that CCC agrees to pay the...

7 CFR 1493.60 - Payment guarantee.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.60 Payment guarantee. (a) CCC's obligation. The payment guarantee will provide that CCC...

7 CFR 1493.60 - Payment guarantee.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.60 Payment guarantee. (a) CCC's obligation. The payment guarantee will provide that CCC agrees to pay the...

7 CFR 1493.520 - Recovery of losses.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... or the exporter's assignee, CCC will notify the importer of CCC's rights under the subrogation... source whatsoever, such monies shall be immediately paid to the Treasurer, CCC. If such monies are not...

7 CFR 1493.520 - Recovery of losses.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... or the exporter's assignee, CCC will notify the importer of CCC's rights under the subrogation... source whatsoever, such monies shall be immediately paid to the Treasurer, CCC. If such monies are not...

7 CFR 1493.320 - Recovery of losses.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... or the exporter's assignee, CCC will notify the foreign bank of CCC's rights under the subrogation... bank or any other source whatsoever, such monies shall be immediately paid to the Treasurer, CCC. If...

7 CFR 1493.520 - Recovery of losses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... or the exporter's assignee, CCC will notify the importer of CCC's rights under the subrogation... source whatsoever, such monies shall be immediately paid to the Treasurer, CCC. If such monies are not...

7 CFR 1493.320 - Recovery of losses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... or the exporter's assignee, CCC will notify the foreign bank of CCC's rights under the subrogation... bank or any other source whatsoever, such monies shall be immediately paid to the Treasurer, CCC. If...

7 CFR 1493.320 - Recovery of losses.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... or the exporter's assignee, CCC will notify the foreign bank of CCC's rights under the subrogation... bank or any other source whatsoever, such monies shall be immediately paid to the Treasurer, CCC. If...

Fresh Water Cyanobacteria Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 as an Anticancer Drug Resource.

PubMed

Srivastava, Akanksha; Tiwari, Ratnakar; Srivastava, Vikas; Singh, Tej Bali; Asthana, Ravi Kumar

2015-01-01

An increasing number of cancer patients worldwide, especially in third world countries, have raised concern to explore natural drug resources, such as the less explored fresh water filamentous cyanobacteria. Six strains of cyanobacteria (Phormidium sp. CCC727, Geitlerinema sp. CCC728, Arthrospira sp. CCC729, Phormidium sp. CCC731, Phormidium sp. CCC730, and Leptolyngbya sp. CCC732) were isolated (paddy fields and ponds in the Banaras Hindu University, campus) and five strains screened for anticancer potential using human colon adenocarcinoma (HT29) and human kidney adenocarcinoma (A498) cancer cell lines. Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 were the most potent as determined by examination of morphological features and by inhibition of growth by graded concentrations of crude extracts and thin-layer chromatography (TLC) eluates. Cell cycle analysis and multiplex assays using cancer biomarkers also confirmed Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 as cancer drug resources. Apoptotic studies in the cells of A498 (cancer) and MCF-10A (normal human epithelial) exposed to crude extracts and TLC fractions revealed no significant impact on MCF-10A cells emphasizing its importance in the development of anticancer drug. Identification of biomolecules from these extracts are in progress.

Fresh Water Cyanobacteria Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 as an Anticancer Drug Resource

PubMed Central

Tiwari, Ratnakar; Srivastava, Vikas

2015-01-01

An increasing number of cancer patients worldwide, especially in third world countries, have raised concern to explore natural drug resources, such as the less explored fresh water filamentous cyanobacteria. Six strains of cyanobacteria (Phormidium sp. CCC727, Geitlerinema sp. CCC728, Arthrospira sp. CCC729, Phormidium sp. CCC731, Phormidium sp. CCC730, and Leptolyngbya sp. CCC732) were isolated (paddy fields and ponds in the Banaras Hindu University, campus) and five strains screened for anticancer potential using human colon adenocarcinoma (HT29) and human kidney adenocarcinoma (A498) cancer cell lines. Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 were the most potent as determined by examination of morphological features and by inhibition of growth by graded concentrations of crude extracts and thin-layer chromatography (TLC) eluates. Cell cycle analysis and multiplex assays using cancer biomarkers also confirmed Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 as cancer drug resources. Apoptotic studies in the cells of A498 (cancer) and MCF-10A (normal human epithelial) exposed to crude extracts and TLC fractions revealed no significant impact on MCF-10A cells emphasizing its importance in the development of anticancer drug. Identification of biomolecules from these extracts are in progress. PMID:26325186

7 CFR 1407.3 - Procurement debarment and suspension.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Procurement debarment and suspension. CCC will proceed under this part when taking action to debar or suspend contractors with CCC or participants or potential participants in CCC's procurement activities. CCC will apply... debarring and suspending official will be the Executive Vice President, CCC, or a designee. ...

7 CFR 1493.260 - Facility payment guarantee.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.260 Facility payment guarantee. (a) CCC's maximum obligation. CCC will agree to... fails to pay under the foreign bank letter of credit or related obligation. The exact amount of CCC's...

7 CFR 1407.3 - Procurement debarment and suspension.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Procurement debarment and suspension. CCC will proceed under this part when taking action to debar or suspend contractors with CCC or participants or potential participants in CCC's procurement activities. CCC will apply... debarring and suspending official will be the Executive Vice President, CCC, or a designee. ...

7 CFR 1407.3 - Procurement debarment and suspension.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Procurement debarment and suspension. CCC will proceed under this part when taking action to debar or suspend contractors with CCC or participants or potential participants in CCC's procurement activities. CCC will apply... debarring and suspending official will be the Executive Vice President, CCC, or a designee. ...

7 CFR 1407.3 - Procurement debarment and suspension.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Procurement debarment and suspension. CCC will proceed under this part when taking action to debar or suspend contractors with CCC or participants or potential participants in CCC's procurement activities. CCC will apply... debarring and suspending official will be the Executive Vice President, CCC, or a designee. ...

7 CFR 1493.260 - Facility payment guarantee.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.260 Facility payment guarantee. (a) CCC's maximum obligation. CCC will agree to... fails to pay under the foreign bank letter of credit or related obligation. The exact amount of CCC's...

7 CFR 1407.3 - Procurement debarment and suspension.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Procurement debarment and suspension. CCC will proceed under this part when taking action to debar or suspend contractors with CCC or participants or potential participants in CCC's procurement activities. CCC will apply... debarring and suspending official will be the Executive Vice President, CCC, or a designee. ...

7 CFR 1493.260 - Facility payment guarantee.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.260 Facility payment guarantee. (a) CCC's maximum obligation. CCC will agree to... fails to pay under the foreign bank letter of credit or related obligation. The exact amount of CCC's...

The Ankle Injury Management (AIM) trial: a pragmatic, multicentre, equivalence randomised controlled trial and economic evaluation comparing close contact casting with open surgical reduction and internal fixation in the treatment of unstable ankle fractures in patients aged over 60 years.

PubMed

Keene, David J; Mistry, Dipesh; Nam, Julian; Tutton, Elizabeth; Handley, Robert; Morgan, Lesley; Roberts, Emma; Gray, Bridget; Briggs, Andrew; Lall, Ranjit; Chesser, Tim Js; Pallister, Ian; Lamb, Sarah E; Willett, Keith

2016-10-01

Close contact casting (CCC) may offer an alternative to open reduction and internal fixation (ORIF) surgery for unstable ankle fractures in older adults. We aimed to (1) determine if CCC for unstable ankle fractures in adults aged over 60 years resulted in equivalent clinical outcome compared with ORIF, (2) estimate cost-effectiveness to the NHS and society and (3) explore participant experiences. A pragmatic, multicentre, equivalence randomised controlled trial incorporating health economic evaluation and qualitative study. Trauma and orthopaedic departments of 24 NHS hospitals. Adults aged over 60 years with unstable ankle fracture. Those with serious limb or concomitant disease or substantial cognitive impairment were excluded. CCC was conducted under anaesthetic in theatre by surgeons who attended training. ORIF was as per local practice. Participants were randomised in 1 : 1 allocation via remote telephone randomisation. Sequence generation was by random block size, with stratification by centre and fracture pattern. Follow-up was conducted at 6 weeks and, by blinded outcome assessors, at 6 months after randomisation. The primary outcome was the Olerud-Molander Ankle Score (OMAS), a patient-reported assessment of ankle function, at 6 months. Secondary outcomes were quality of life (as measured by the European Quality of Life 5-Dimensions, Short Form questionnaire-12 items), pain, ankle range of motion and mobility (as measured by the timed up and go test), patient satisfaction and radiological measures. In accordance with equivalence trial US Food and Drug Administration guidance, primary analysis was per protocol. We recruited 620 participants, 95 from the pilot and 525 from the multicentre phase, between June 2010 and November 2013. The majority of participants, 579 out of 620 (93%), received the allocated treatment; 52 out of 275 (19%) who received CCC later converted to ORIF because of loss of fracture reduction. CCC resulted in equivalent ankle function compared with ORIF at 6 months {OMAS 64.5 points [standard deviation (SD) 22.4 points] vs. OMAS 66.0 points (SD 21.1 points); mean difference -0.65 points, 95% confidence interval (CI) -3.98 to 2.68 points; standardised effect size -0.04, 95% CI -0.23 to 0.15}. There were no differences in quality of life, ankle motion, pain, mobility and patient satisfaction. Infection and/or wound problems were more common with ORIF [29/298 (10%) vs. 4/275 (1%)], as were additional operating theatre procedures [17/298 (6%) vs. 3/275 (1%)]. Malunion was more common with CCC [38/249 (15%) vs. 8/274 (3%); p  < 0.001]. Malleolar non-union was lower in the ORIF group [lateral: 0/274 (0%) vs. 8/248 (3%); p  = 0.002; medial: 3/274 (1%) vs. 18/248 (7%); p  < 0.001]. During the trial, CCC showed modest mean cost savings [NHS mean difference -£644 (95% CI -£1390 to £76); society mean difference -£683 (95% CI -£1851 to £536)]. Estimates showed some imprecision. Incremental quality-adjusted life-years following CCC were no different from ORIF. Over common willingness-to-pay thresholds, the probability that CCC was cost-effective was very high (> 95% from NHS perspective and 85% from societal perspective). Experiences of treatments were similar; both groups endured the impact of fracture, uncertainty regarding future function and the need for further interventions. Assessors at 6 weeks were necessarily not blinded. The learning-effect analysis was inconclusive because of limited CCC applications per surgeon. CCC provides a clinically equivalent outcome to ORIF at reduced cost to the NHS and to society at 6 months. Longer-term follow-up of trial participants is under way to address concerns over potential later complications or additional procedures and their potential to impact on ankle function. Further study of the patient factors, radiological fracture patterns and outcomes, treatment responses and prognosis would also contribute to understanding the treatment pathway. Current Controlled Trials ISRCTN04180738. The National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 20, No. 75. See the NIHR Journals Library website for further project information. This report was developed in association with the National Institute for Health Research Oxford Biomedical Research Unit funding scheme. The pilot phase was funded by the AO Research Foundation.

Ankle Injury Management (AIM): design of a pragmatic multi-centre equivalence randomised controlled trial comparing Close Contact Casting (CCC) to Open surgical Reduction and Internal Fixation (ORIF) in the treatment of unstable ankle fractures in patients over 60 years.

PubMed

Willett, Keith; Keene, David J; Morgan, Lesley; Gray, Bridget; Handley, Robert; Chesser, Tim; Pallister, Ian; Tutton, Elizabeth; Knox, Christopher; Lall, Ranjit; Briggs, Andrew; Lamb, Sarah E

2014-03-12

Ankle fractures account for 9% of all fractures with a quarter of these occurring in adults over 60 years. The short term disability and long-term consequences of this injury can be considerable. Current opinion favours open reduction and internal fixation (ORIF) over non-operative treatment (fracture manipulation and the application of a standard moulded cast) for older people. Both techniques are associated with complications but the limited published research indicates higher complication rates of fracture malunion (poor position at healing) with casting. The aim of this study is to compare ORIF with a modification of existing casting techniques, Close Contact Casting (CCC). We propose that CCC may offer an equivalent functional outcome to ORIF and avoid the risks associated with surgery. This study is a pragmatic multi-centre equivalence randomised controlled trial. 620 participants will be randomised to receive ORIF or CCC after sustaining an isolated displaced unstable ankle fracture. Participants will be recruited from a minimum of 20 National Health Service (NHS) acute hospitals throughout England and Wales. Participants will be aged over 60 years and be ambulatory prior to injury. Follow-up will be at six weeks and six months after randomisation. The primary outcome is the Olerud & Molander Ankle Score, a functional patient reported outcome measure, at 6 months. Follow-up will also include assessments of mobility, ankle range of movement, health related quality of life and complications. The six-month follow-up will be conducted face-to-face by an assessor blinded to the allocated intervention. A parallel economic evaluation will consider both a health service and a broader societal perspective including the individual and their family. In order to explore patient experience of their treatment and recovery, a purposive sample of 40 patients will also be interviewed using a semi-structured interview schedule between 6-10 weeks post treatment. This multicentre study was open to recruitment July 2010 and recruitment is due to be completed in December 2013. Current Controlled Trials ISRCTN04180738.

7 CFR 1435.401 - CCC sugar inventory disposition.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false CCC sugar inventory disposition. 1435.401 Section... CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS SUGAR PROGRAM Disposition of CCC Inventory § 1435.401 CCC sugar inventory disposition. (a) CCC will dispose of inventory in the following...

7 CFR 1488.13 - CCC drafts.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false CCC drafts. 1488.13 Section 1488.13 Agriculture... Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Bank Obligations and Repayment § 1488.13 CCC drafts. CCC will draw one draft for each payment due under...

7 CFR 1488.14 - Interest charges.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Bank Obligations and Repayment § 1488.14 Interest charges. The account receivable assigned to CCC and..., CCC after consultation with the Controller, CCC, to be in the interest of CCC, be lower than the...

7 CFR 1488.13 - CCC drafts.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false CCC drafts. 1488.13 Section 1488.13 Agriculture... Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Bank Obligations and Repayment § 1488.13 CCC drafts. CCC will draw one draft for each payment due under...

7 CFR 1488.14 - Interest charges.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Bank Obligations and Repayment § 1488.14 Interest charges. The account receivable assigned to CCC and..., CCC after consultation with the Controller, CCC, to be in the interest of CCC, be lower than the...

Structures, fragmentation, and protonation of trideoxynucleotide CCC mono- and dianions.

PubMed

Anichina, Janna; Feil, Stefan; Uggerud, Einar; Bohme, Diethard K

2008-07-01

Both quantum chemical calculations and ESI mass spectrometry are used here to explore the gas-phase structures, energies, and stabilities against collision-induced dissociation of a relatively small model DNA molecule--a trideoxynucleotide with the sequence CCC, in its singly and doubly deprotonated forms, (CCC-H)(-) and (CCC-2H)(2-), respectively. Also, the gas-phase reactivity of these two anions was measured with HBr, a potential proton donor, using an ESI/SIFT/QqQ instrument. The computational results provide insight into the gas-phase structures of the electrosprayed (CCC-2H)(2-) and (CCC-H)(-) anions and the neutral CCC, as well as the proton affinities of the di- and monoanions. The dianion (CCC-2H)(2-) was found to dissociate upon CID by charge separation via two competing channels: separation into deprotonated cytosine (C-H)(-) and (CCC-(C-H)-2H)(-), and by w(1)(-)/a(2)(-) cleavage of the backbone. The monoanion (CCC-H)(-) loses a neutral cytosine upon CID, and an H/D-exchangeable proton, presumably residing on one of the phosphate groups, is transferred to the partially liberated (C-H)(-) before dissociation. This was confirmed by MS/MS experiments with the deuterated analog. The reaction of (CCC-2H)(2-) with HBr was observed to be rapid, k=(1.4+/-0.4) x 10(-9) cm(3) molecule(-1) s(-1), and to proceed both by addition (78%) and by proton transfer (22%) while (CCC-H)(-) reacts only by HBr addition, k=(7.1+/-2.1) x 10(-10) cm(3) molecule(-1) s(-1). This is in accord with the computed proton affinities of (CCC-2H)(2-) and (CCC-H)(-) anions that bracket the known proton affinity of Br(-).

7 CFR 1494.801 - Enforcement and termination of agreements with CCC.

Code of Federal Regulations, 2010 CFR

2010-01-01

... it had been placed aboard the export carrier. In making the decision whether to hold an exporter harmless pursuant to this paragraph, CCC may consider any information available to CCC, including any... may be incurred by CCC. (d) Decision to hold the exporter harmless for liquidated damages. CCC will...

7 CFR 1494.801 - Enforcement and termination of agreements with CCC.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Enforcement and termination of agreements with CCC... Enhancement Program Operations § 1494.801 Enforcement and termination of agreements with CCC. (a) Performance in accordance with an Agreement with CCC. (1) An exporter which enters into an Agreement with CCC...

7 CFR 1486.406 - Will CCC make advance payments to Recipients?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Will CCC make advance payments to Recipients? 1486... PROGRAM Contributions and Reimbursements § 1486.406 Will CCC make advance payments to Recipients? (a) Policy. In general, CCC operates the EMP on a cost reimbursable basis. (b) Exception. Upon request, CCC...

7 CFR 1401.3 - Payments to persons with outstanding CCC loans.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Payments to persons with outstanding CCC loans. 1401... KIND PAYMENTS, AND OTHER FORMS OF PAYMENT § 1401.3 Payments to persons with outstanding CCC loans. (a) Persons with outstanding CCC loans who are eligible to receive payments from CCC, including a person...

7 CFR 1435.503 - In-kind payments.

Code of Federal Regulations, 2011 CFR

2011-01-01

... (PIK) Program § 1435.503 In-kind payments. (a) CCC will, through such methods as CCC deems appropriate, make payments in the form of sugar held in CCC inventory. (b) To the maximum extent practicable, CCC will use its inventory in making an in-kind payment based on the following priority: (1) CCC-owned...

7 CFR 1435.503 - In-kind payments.

Code of Federal Regulations, 2012 CFR

2012-01-01

... (PIK) Program § 1435.503 In-kind payments. (a) CCC will, through such methods as CCC deems appropriate, make payments in the form of sugar held in CCC inventory. (b) To the maximum extent practicable, CCC will use its inventory in making an in-kind payment based on the following priority: (1) CCC-owned...

7 CFR 1401.3 - Payments to persons with outstanding CCC loans.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Payments to persons with outstanding CCC loans. 1401... KIND PAYMENTS, AND OTHER FORMS OF PAYMENT § 1401.3 Payments to persons with outstanding CCC loans. (a) Persons with outstanding CCC loans who are eligible to receive payments from CCC, including a person...

7 CFR 1494.601 - Acceptance of offers by CCC.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Acceptance of offers by CCC. 1494.601 Section 1494... Program Operations § 1494.601 Acceptance of offers by CCC. (a) Establishment of acceptable sales prices and CCC bonuses. For each Invitation, CCC will establish sales prices for the eligible commodity and...

7 CFR 1488.13 - CCC drafts.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false CCC drafts. 1488.13 Section 1488.13 Agriculture... Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Bank Obligations and Repayment § 1488.13 CCC drafts. CCC will draw one draft for each payment due under bank obligations. If any...

7 CFR 1488.13 - CCC drafts.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false CCC drafts. 1488.13 Section 1488.13 Agriculture... Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Bank Obligations and Repayment § 1488.13 CCC drafts. CCC will draw one draft for each payment due under bank obligations. If any...

7 CFR 1401.3 - Payments to persons with outstanding CCC loans.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Payments to persons with outstanding CCC loans. 1401... KIND PAYMENTS, AND OTHER FORMS OF PAYMENT § 1401.3 Payments to persons with outstanding CCC loans. (a) Persons with outstanding CCC loans who are eligible to receive payments from CCC, including a person...

7 CFR 1435.503 - In-kind payments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... (PIK) Program § 1435.503 In-kind payments. (a) CCC will, through such methods as CCC deems appropriate, make payments in the form of sugar held in CCC inventory. (b) To the maximum extent practicable, CCC will use its inventory in making an in-kind payment based on the following priority: (1) CCC-owned...

7 CFR 1494.801 - Enforcement and termination of agreements with CCC.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Enforcement and termination of agreements with CCC... Enhancement Program Operations § 1494.801 Enforcement and termination of agreements with CCC. (a) Performance in accordance with an Agreement with CCC. (1) An exporter which enters into an Agreement with CCC...

7 CFR 1401.3 - Payments to persons with outstanding CCC loans.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Payments to persons with outstanding CCC loans. 1401... KIND PAYMENTS, AND OTHER FORMS OF PAYMENT § 1401.3 Payments to persons with outstanding CCC loans. (a) Persons with outstanding CCC loans who are eligible to receive payments from CCC, including a person...

7 CFR 1486.406 - Will CCC make advance payments to Recipients?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Will CCC make advance payments to Recipients? 1486... PROGRAM Contributions and Reimbursements § 1486.406 Will CCC make advance payments to Recipients? (a) Policy. In general, CCC operates the EMP on a cost reimbursable basis. (b) Exception. Upon request, CCC...

7 CFR 1494.801 - Enforcement and termination of agreements with CCC.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Enforcement and termination of agreements with CCC... Enhancement Program Operations § 1494.801 Enforcement and termination of agreements with CCC. (a) Performance in accordance with an Agreement with CCC. (1) An exporter which enters into an Agreement with CCC...

7 CFR 1401.3 - Payments to persons with outstanding CCC loans.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Payments to persons with outstanding CCC loans. 1401... KIND PAYMENTS, AND OTHER FORMS OF PAYMENT § 1401.3 Payments to persons with outstanding CCC loans. (a) Persons with outstanding CCC loans who are eligible to receive payments from CCC, including a person...

7 CFR 1488.13 - CCC drafts.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false CCC drafts. 1488.13 Section 1488.13 Agriculture... Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Bank Obligations and Repayment § 1488.13 CCC drafts. CCC will draw one draft for each payment due under bank obligations. If any...

7 CFR 1494.601 - Acceptance of offers by CCC.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Acceptance of offers by CCC. 1494.601 Section 1494... Program Operations § 1494.601 Acceptance of offers by CCC. (a) Establishment of acceptable sales prices and CCC bonuses. For each Invitation, CCC will establish sales prices for the eligible commodity and...

7 CFR 1435.503 - In-kind payments.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (PIK) Program § 1435.503 In-kind payments. (a) CCC will, through such methods as CCC deems appropriate, make payments in the form of sugar held in CCC inventory. (b) To the maximum extent practicable, CCC will use its inventory in making an in-kind payment based on the following priority: (1) CCC-owned...

The correlation between lymphocyte/monocyte ratio and coronary collateral circulation in stable coronary artery disease patients.

PubMed

Kurtul, Alparslan; Duran, Mustafa

2017-01-01

Coronary collateral circulation (CCC) has an important impact on cardiovascular prognosis and well-developed CCC is associated with better clinical outcomes. We investigated whether lymphocyte/monocyte ratio (LMR) has an association with CCC in patients with stable coronary artery disease (SCAD). The study population consisted of 245 patients with SCAD. Patients were classified into a poor CCC group (Rentrop grades 0/1, n = 87), or good CCC group (Rentrop grades 2/3, n = 158). LMR values were significantly higher in patients with good CCC than in those with poor CCC (4.41 ± 1.58 vs 2.76 ± 1.10; p < 0.001). In receiver operating characteristic analysis, optimal cutoff of LMR for predicting well-developed CCC was 3.38. In multivariate analysis, LMR >3.38 (OR 4.637; p = 0.004), high sensitivity C-reactive protein (OR 0.810, p < 0.001), dyslipidemia (OR 2.485; p = 0.039), and presence of chronic total occlusion (OR 16.836; p < 0.001) were independent predictors of well-developed CCC. Increased LMR predicts well-developed CCC in SCAD patients.

Spinoculation Enhances HBV Infection in NTCP-Reconstituted Hepatocytes.

PubMed

Yan, Ran; Zhang, Yongmei; Cai, Dawei; Liu, Yuanjie; Cuconati, Andrea; Guo, Haitao

2015-01-01

Hepatitis B virus (HBV) infection and its sequelae remain a major public health burden, but both HBV basic research and the development of antiviral therapeutics have been hindered by the lack of an efficient in vitro infection system. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the HBV receptor. We herein report that we established a NTCP-complemented HepG2 cell line (HepG2-NTCP12) that supports HBV infection, albeit at a low infectivity level following the reported infection procedures. In our attempts to optimize the infection conditions, we found that the centrifugation of HepG2-NTCP12 cells during HBV inoculation (termed "spinoculation") significantly enhanced the virus infectivity. Moreover, the infection level gradually increased with accelerated speed of spinoculation up to 1,000g tested. However, the enhancement of HBV infection was not significantly dependent upon the duration of centrifugation. Furthermore, covalently closed circular (ccc) DNA was detected in infected cells under optimized infection condition by conventional Southern blot, suggesting a successful establishment of HBV infection after spinoculation. Finally, the parental HepG2 cells remained uninfected under HBV spinoculation, and HBV entry inhibitors targeting NTCP blocked HBV infection when cells were spinoculated, suggesting the authentic virus entry mechanism is unaltered under centrifugal inoculation. Our data suggest that spinoculation could serve as a standard protocol for enhancing the efficiency of HBV infection in vitro.

Spinoculation Enhances HBV Infection in NTCP-Reconstituted Hepatocytes

PubMed Central

Yan, Ran; Zhang, Yongmei; Cai, Dawei; Liu, Yuanjie; Cuconati, Andrea; Guo, Haitao

2015-01-01

Hepatitis B virus (HBV) infection and its sequelae remain a major public health burden, but both HBV basic research and the development of antiviral therapeutics have been hindered by the lack of an efficient in vitro infection system. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the HBV receptor. We herein report that we established a NTCP-complemented HepG2 cell line (HepG2-NTCP12) that supports HBV infection, albeit at a low infectivity level following the reported infection procedures. In our attempts to optimize the infection conditions, we found that the centrifugation of HepG2-NTCP12 cells during HBV inoculation (termed “spinoculation”) significantly enhanced the virus infectivity. Moreover, the infection level gradually increased with accelerated speed of spinoculation up to 1,000g tested. However, the enhancement of HBV infection was not significantly dependent upon the duration of centrifugation. Furthermore, covalently closed circular (ccc) DNA was detected in infected cells under optimized infection condition by conventional Southern blot, suggesting a successful establishment of HBV infection after spinoculation. Finally, the parental HepG2 cells remained uninfected under HBV spinoculation, and HBV entry inhibitors targeting NTCP blocked HBV infection when cells were spinoculated, suggesting the authentic virus entry mechanism is unaltered under centrifugal inoculation. Our data suggest that spinoculation could serve as a standard protocol for enhancing the efficiency of HBV infection in vitro. PMID:26070202

7 CFR 1486.406 - Will CCC make advance payments to Recipients?

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Will CCC make advance payments to Recipients? 1486... Reimbursements § 1486.406 Will CCC make advance payments to Recipients? (a) Policy. In general, CCC operates the EMP on a cost reimbursable basis. (b) Exception. Upon request, CCC may make advance payments to a...

7 CFR 1494.801 - Enforcement and termination of agreements with CCC.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Enforcement and termination of agreements with CCC... CCC. (a) Performance in accordance with an Agreement with CCC. (1) An exporter which enters into an Agreement with CCC must ensure that the eligible commodity is exported from the U.S. and enters the eligible...

7 CFR 1486.406 - Will CCC make advance payments to Recipients?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Will CCC make advance payments to Recipients? 1486... Reimbursements § 1486.406 Will CCC make advance payments to Recipients? (a) Policy. In general, CCC operates the EMP on a cost reimbursable basis. (b) Exception. Upon request, CCC may make advance payments to a...

7 CFR 1486.406 - Will CCC make advance payments to Recipients?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Will CCC make advance payments to Recipients? 1486... Reimbursements § 1486.406 Will CCC make advance payments to Recipients? (a) Policy. In general, CCC operates the EMP on a cost reimbursable basis. (b) Exception. Upon request, CCC may make advance payments to a...

The relationship of plasma miR-503 and coronary collateral circulation in patients with coronary artery disease.

PubMed

Fei, Yu; Hou, Jianhua; Xuan, Wei; Zhang, Chenghua; Meng, Xiuping

2018-06-02

Although angiogenesis plays an important role in coronary collateral circulation (CCC) formation and there are many determinants of coronary angiogenesis, they cannot fully explain the mechanism of CCC formation or as potent biomarker for CCC status. Therefore, there is of great clinical significance to identify the novel molecules associated with CCC. Previously, miR-503 exerts anti-angiogenesis effect via inhibition of VEGF-A and its expression is associated with many angiogenesis-related factors. Thus, we aimed to investigate the relationship of plasma miR-503 with CCC formation as well as its predictive power for CCC status in patients with coronary artery disease. Among patients who underwent coronary angiography with coronary artery disease and a stenosis of ≥90% were included in our study. Collateral degree was graded according to Rentrop Cohen classification. The patients were divided to good CCC group (grade 2 or 3) and poor CCC group (grade 0 or 1) according to Rentrop grade. We investigated the plasma levels of miR-503 and VEGF-A by ELISA or q RT-PCR, respectively. In addition, we assayed the correlations of plasma miR-503 with VEGF-A or Rentrop grade using the spearman correlation test and its predictive power by receiver operating characteristic (ROC) and binary logistical regression analysis. Our data showed that plasma VEGF-A was significantly higher in good CCC group than that in poor group. Plasma miR-503 was lower in CAD patients with good CCC or poor CCC compared with control subjects and lowest in good CCC group. In addition, miR-503 negatively correlated with VEGF-A and Rentrop grade, respectively. Moreover, miR-503 displayed more potent predictive power for CCC status than VEGF-A, but its sensitivity and specificity for CCC status were only 72.4 or 60.9%, respectively. Lower plasma miR-503 level was related to better CCC formation, accompanied by up-regulation of VEGF-A. In addition, miR-503 displayed potent predictive power for CCC status, but its sensitivity and specificity were not high enough, indicating that miR-503 might be as an additional prognosis biomarker for CCC. Copyright © 2017. Published by Elsevier Inc.

Rapid screening for plasmid DNA.

PubMed

Hughes, C; Meynell, G G

1977-03-07

A procedure is described for demonstrating plasmid DNA and its molecular weight, based on rate zonal centrifugation of unlabelled DNA in neutral sucrose gradients containing a low concentration of ethidium bromide. Each DNA species is then visualized as a discrete fluorescent band when the centrifuge tube is illuminated with ultra-violet light. Plasmids exist as closed circular and as relaxed circular molecules, which sediment separately, but during preparation of lysates, closed circular molecules are nicked so that each plasmid forms only a single band of relaxed circles within the gradient.

Evaluation of an interlaced triple procedure: penetrating keratoplasty, extracapsular cataract extraction, and nonopen-sky intraocular lens implantation.

PubMed

Yang, Shuo; Wang, Bin; Zhang, Yangyang; Zhai, Hualei; Wang, Junyi; Wang, Shuang; Xie, Lixin

2017-09-01

To evaluate an interlaced triple procedure that involved penetrating keratoplasty (PKP), extracapsular cataract extraction (ECCE) using diathermy capsulotomy, and nonopen-sky intraocular lens (IOL) implantation.This retrospective study involved data from 34 patients who were diagnosed with severe corneal opacities and cataracts. These patients were divided into an interlaced procedure group (21 patients) and a traditional procedure group (13 patients). In the interlaced group, the method of continuous curvilinear capsulorhexis (CCC) was completed via diathermy capsulotomy. The donor corneal button was sutured at 8 positions (at equal intervals) using 10-0 nylon sutures, and the IOL was inserted into the capsular bag using a closed anterior chamber approach at the 10:30 to 12 o'clock positions between the sutures. In the traditional group, CCC was completed using side-port capsular forceps, and the IOL was implanted using an open anterior chamber approach.In the interlaced group, the CCC, open-sky, and total operation times were significantly shorter than in the traditional group (P < .05). Neither the best-corrected visual acuity (BCVA) nor corneal endothelial cell density was significantly different between the groups at 1 and 6 months after the operation.This interlaced triple procedure for the treatment of corneal diseases with cataracts appears to be feasible and practical.

On the nature and origin of the oxalate package in Solanum sisymbriifolium anthers.

PubMed

Burrieza, Hernán Pablo; López-Fernández, María Paula; Láinez, Verónica; Montenegro, Teresita; Maldonado, Sara

2010-11-01

This is a detailed study carried out in Solanum sisymbriifolium Lam. on the development of the circular cell cluster (CCC) during crystal deposition, as well as the composition of the crystals. Light microscopy and scanning and transmission electron microscopy (TEM) were used to characterize tissue throughout anther development. Energy dispersive X-ray analysis (EDAX) allowed the determination of the elemental composition of crystals that form in the CCC region, and infrared and x-ray diffraction analysis were used to specify the crystal salt composition. TEM analysis revealed that the crystals originated simultaneously within the vacuoles in association with a paracrystalline protein. Prior to the appearance of protein within vacuoles, protein paracrystals were visible in both rough endoplasmic reticulum and vesicles with ribosomes on their membranes. In vacuoles, paracrystals constitute nucleation sites for druse crystals formation. EDAX revealed that C, O, and Ca were the main elements, and K, Cl, Mg, P, S, and Si, the minor elements. X-ray powder diffraction of crystals detected the predominant presence of calcium oxalate, but also vestiges of calcite, quartz, and sylvite. The calcium oxalate coexisted in the three chemical forms, that is, whewellite, weddellite, and caoxite. Infrared spectrophotometry identified bands that characterize O-C-O, H-O, C-H bonds, all of calcium oxalate, and Si-O-Si, of quartz. These results were compared with studies of anthers carried out in other Solanaceae genera.

7 CFR 1493.230 - Eligible transactions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.230 Eligible transactions. (a) Program announcements. From time to time CCC... markets, the maximum amount, in U.S. dollars, of guarantee exposure that CCC will undertake, and may...

7 CFR 1493.290 - Proof of entry.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP... certified or other translation acceptable to CCC. Records acceptable to meet this requirement include: (1... documentation deemed acceptable by CCC: (i) Showing that the goods entered the emerging market; (ii) Identifying...

7 CFR 1493.400 - General statement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... restrictions and criteria set forth at subpart A for the Commodity Credit Corporation (CCC) Export Credit... to provide financing without CCC's guarantee. The program is operated in a manner intended not to...

7 CFR 1493.400 - General statement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... restrictions and criteria set forth at subpart A for the Commodity Credit Corporation (CCC) Export Credit... to provide financing without CCC's guarantee. The program is operated in a manner intended not to...

7 CFR 1493.100 - Proof of entry.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493... a certified or other translation acceptable to CCC. Records acceptable to meet this requirement...

7 CFR 1493.290 - Proof of entry.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP... certified or other translation acceptable to CCC. Records acceptable to meet this requirement include: (1... documentation deemed acceptable by CCC: (i) Showing that the goods entered the emerging market; (ii) Identifying...

7 CFR 1493.290 - Proof of entry.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP... certified or other translation acceptable to CCC. Records acceptable to meet this requirement include: (1... documentation deemed acceptable by CCC: (i) Showing that the goods entered the emerging market; (ii) Identifying...

7 CFR 1493.230 - Eligible transactions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.230 Eligible transactions. (a) Program announcements. From time to time CCC... markets, the maximum amount, in U.S. dollars, of guarantee exposure that CCC will undertake, and may...

7 CFR 1493.230 - Eligible transactions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC.... From time to time CCC will issue program announcements indicating the availability of facility payment... the emerging markets, the maximum amount, in U.S. dollars, of guarantee exposure that CCC will...

7 CFR 1493.30 - Information required for program participation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.30 Information required for program participation. Before CCC...

7 CFR 1493.450 - Payment guarantee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.450 Payment guarantee. (a) CCC's obligation. The payment guarantee will provide that CCC agrees to pay the exporter or the exporter's assignee an amount...

7 CFR 1493.230 - Eligible transactions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.230 Eligible transactions. (a) Program announcements. From time to time CCC... markets, the maximum amount, in U.S. dollars, of guarantee exposure that CCC will undertake, and may...

7 CFR 1493.100 - Proof of entry.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493... a certified or other translation acceptable to CCC. Records acceptable to meet this requirement...

7 CFR 1493.450 - Payment guarantee.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.450 Payment guarantee. (a) CCC's obligation. The payment guarantee will provide that CCC agrees to pay the exporter or the exporter's assignee an amount...

Conical coils counter-current chromatography for preparative isolation and purification of tanshinones from Salvia miltiorrhiza Bunge.

PubMed

Liang, Junling; Meng, Jie; Guo, Mengzhe; Yang, Zhi; Wu, Shihua

2013-05-03

Modern counter-current chromatography (CCC) originated from the helical coil planet centrifuge. Recently, spiral coils were found to possess higher separation efficiency in both the retention of stationary phase and solutes resolution than other CCC coils like the helical and toroidal coils used on type-J CCC and cross-axis CCC. In this work, we built a novel conical coil CCC for the preparative isolation and purification of tanshinones from Salvia miltiorrhiza Bunge. The conical coils were wound on three identical upright tapered holders in head-to-tail and left-handed direction and connected in series. Compared with helical and spiral coil CCC, conical coil CCC not only placed CCC column in a two-dimensional centrifugal field, but also provided a potential centrifugal force gradient both in axial and radial directions. The extra centrifugal gradient made mobile phase move faster and enabled CCC much higher retention of stationary phase and better resolution. As a result, higher efficiency has been obtained with the solvent system of hexane-ethyl acetate-methanol-water (HEMWat) with the volume ratio of 5:5:7:3 by using conical coil CCC apparatus. Four tanshinones, including cryptotanshinone (1), tanshinone I (2), 1,2-dihydrotanshinquinone (3) and tanshinone IIA (4), were well resolved from 500mg to 1g crude samples with high purity. Furthermore, the conical coil CCC can make a much higher solid phase retention, which makes it to be a powerful separation tool with high throughput. This is the first report about conical coil CCC for separation of tanshinones and it may also be an important advancement for natural products isolation. Copyright © 2013 Elsevier B.V. All rights reserved.

EFFECT OF COLLA CORNUS CERVI COMBINED WITH LV-MEDIATED BMP7 TRANSFECTED BMSCs ON ANFH IN RATS.

PubMed

Wang, Ping; Shi, Bin; Gao, Zhi-Hui; Sun, Tie-Feng; Yang, Wu-Bin; Han, Shu-Fang; Liu, Peng; Wang, Lei-Lei; Zhao, Bo-Nian; Wang, Dan-Dan

2016-11-01

In the present study, we investigated the combined effect of Colla Comus Cervi (CCC) and BMP7-overexpressing bone marrow-derived mesenchymal stem cells (BMSCs) on osteogenic induction and the treatment of avascular necrosis of the femoral head (ANFH). BMSCs were isolated from rats. BMP7-overexpressing BMSCs were generated by lentiviral-mediated gene transduction. Cell proliferation, alkaline phosphatase (ALP) activity, osteogenesis related gene expression, osteocalcin levels, and calcified nodules were quantified and compared between four groups: untreated controls, BMSCs cultured with CCC complex medium, BMP7-overexpressing BMSCs, and BMP7-overexpressing BMSCs cultured with CCC complex medium (CCC+BMP7). CCC+BMP7 BMSCs showed higher proliferation rate. ALP activity and osteaocalcin content were significantly increased in CCC+BMP7 BMSCs. The osteogenesis related genes, COLI, and integrin-α2, -α5, and -β1, were expressed significantly higher in CCC+BMP7 BMSCs. The number of calcified nodules in the CCC+BMP7 group was significantly higher than that in other groups. For in vivo assays, ANFH was induced in rats, and BMSCs were injected into the femoral head of the lower left extremity. In rats with induced ANFH, general observation scores of the CCC+BMP7 injected group were significantly higher than the model group. X-ray and microscopic observations revealed that ANFH was significantly improved and femoral head cells gradually recovered in rats treated with CCC+BMP7 BMSCs. Our results suggest that CCC+BMP7 significantly promote the proliferation and osteogenic differentiation of BMSCs in vitm. CCC+BMP7 BMSCs promote the ability of repairing ANFH in rats, providing a new therapeutic paradigm for the treatment of ANFH.

Comparison of Clinical Characteristic and Prognosis between Ovarian Clear Cell Carcinoma and Serous Carcinoma: A 10-Year Cohort Study of Chinese Patients.

PubMed

Ye, Shuang; Yang, Jiaxin; You, Yan; Cao, Dongyan; Huang, Huifang; Wu, Ming; Chen, Jie; Lang, Jinghe; Shen, Keng

2015-01-01

To compare the clinicopathologic features and prognosis of Chinese patients with ovarian clear cell carcinoma (CCC) and serous carcinoma (SC). A retrospective cohort study was designed to investigate the clinicopathologic characteristic and prognosis of patients with CCC and SC who were diagnosed and treated in in a tertiary referral center (Peking Union Medical College Hospital) between 1999 and 2009. The Kaplan-Meier method and Cox regression were employed in the survival analysis. A total of 504 cases were included in the study, comprising 197 cases of CCC and 307 cases of SC. The mean age of the patients with SC was greater than of CCC patients (3.6±0.94, P<0.001). Patients with CCC were more likely to be early-stage and optimally debulked (P<0.001). Regarding cancer-antigen 125, 22% of the patients with CCC had normal values, and the level was significantly lower than in patients with SC (P<0.001). More CCC patients had platinum-resistant tumors compared with platinum-sensitive disease (45.7% in CCC vs. 61.0% in SC [P=0.008]). The 5-year survival rate was 51.2% in the CCC group vs. 49.8% in the SC group (P=0.428). Patients with advanced CCC had a statistically significant poorer overall survival (OS) compared with their SC counterparts (38.0 vs. 52.0 months; hazard ratio 1.584, 95% confidence interval [CI] 1.167-2.150, P=0.003). However, the advantage of improved progression-free survival (PFS) existed across all stages. Women with ovarian CCC presented at a younger age and early stage. Patients with ovarian CCC also had improved PFS, but they had similar OS compared to patients with SC. However, patients with advanced CCC had decreased survival.

Scleral Lens Clearance Assessment with Biomicroscopy and Anterior Segment Optical Coherence Tomography.

PubMed

Yeung, Debby; Sorbara, Luigina

2018-01-01

It is important to be able to accurately estimate the central corneal clearance when fitting scleral contact lenses. Tools available have intrinsic biases due to the angle of viewing, and therefore an idea of the amount of error in estimation will benefit the fitter. To compare the accuracy of observers' ability to estimate scleral contact lens central corneal clearance (CCC) with biomicroscopy to measurements using slit-lamp imaging and anterior segment optical coherence tomography (AS-OCT). In a Web-based survey with images of four scleral lens fits obtained with a slit-lamp video imaging system, participants were asked to estimate the CCC. Responses were compared with known values of CCC of these images determined with an image-processing program (digital CCC) and using the AS-OCT (AS-OCT CCC). Bland-Altman plots and concordance correlation coefficients were used to assess the agreement of CCC measured by the various methods. Sixty-six participants were categorized for analysis based on the amount of experience with scleral lens fitting into novice, intermediate, or advanced fitters. Comparing the estimated CCC to the digital CCC, all three groups overestimated by an average of +27.3 ± 67.3 μm. The estimated CCC was highly correlated to the digital CCC (0.79, 0.92, and 0.94 for each group, respectively). Compared with the CCC measurements using AS-OCT, the three groups of participants overestimated by +103.3 μm and had high correlations (0.79, 0.93, and 0.94 for each group). Results from this study validate the ability of contact lens practitioners to observe and estimate the CCC in scleral lens fittings through the use of biomicroscopic viewing. Increasing experience with scleral lens fitting does not improve the correlation with measured CCC from digital or the AS-OCT. However, the intermediate and advanced groups display significantly less inter-observer variability compared with the novice group.

7 CFR 1493.450 - Payment guarantee.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.450 Payment guarantee. (a) CCC's obligation. The payment guarantee will provide that CCC agrees to pay the exporter or the exporter's assignee an amount not to exceed the guaranteed...

7 CFR 1493.290 - Proof of entry.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee... accompanied by a certified or other translation acceptable to CCC. Records acceptable to meet this requirement... documentation deemed acceptable by CCC: (i) Showing that the goods entered the emerging market; (ii) Identifying...

7 CFR 1493.470 - Evidence of export.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... provide CCC an evidence of export report for each shipment made under the payment guarantee. This report... participation in any of the following CCC or USDA export program: Export Enhancement Program, Dairy Export...

7 CFR 1493.210 - Definition of terms.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... guarantee. CCC. The Commodity Credit Corporation, an agency and instrumentality of the United States within... telephone and facsimile numbers of contacts within FAS/USDA and CCC. The Contacts P/R also contains details...

7 CFR 1493.310 - Payment for loss.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.310 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of the information and documents required under § 1493.300, CCC will...

7 CFR 1493.260 - Facility payment guarantee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.260 Facility payment guarantee. (a) CCC's maximum obligation. CCC will agree to pay the exporter or the exporter's assignee an amount not to exceed the...

7 CFR 1493.40 - Application for payment guarantee.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program..., contract loading tolerance and, if necessary, a request for CCC to reserve coverage up to the maximum...

7 CFR 1493.130 - Recovery of losses.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.130 Recovery of losses. (a) Notification. Upon payment of loss to the exporter or the exporter's assignee, CCC...

7 CFR 1493.210 - Definition of terms.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... guarantee. CCC. The Commodity Credit Corporation, an agency and instrumentality of the United States within... telephone and facsimile numbers of contacts within FAS/USDA and CCC. The Contacts P/R also contains details...

7 CFR 1493.470 - Evidence of export.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... provide CCC an evidence of export report for each shipment made under the payment guarantee. This report... participation in any of the following CCC or USDA export program: Export Enhancement Program, Dairy Export...

7 CFR 1493.10 - General statement.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.10... GSM-102 and GSM-103 programs of the Commodity Credit Corporation (CCC) were developed to expand U.S...

7 CFR 1493.310 - Payment for loss.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.310 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of the information and documents required under § 1493.300, CCC will determine whether or...

7 CFR 1493.450 - Payment guarantee.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.450 Payment guarantee. (a) CCC's obligation. The payment guarantee will provide that CCC agrees to pay the exporter or the exporter's assignee an amount not to exceed the guaranteed...

7 CFR 1493.120 - Payment for loss.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.120 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of the information and...

7 CFR 1493.120 - Payment for loss.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.120 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of...

7 CFR 1493.510 - Payment for loss.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.510 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of the information and documents required under § 1493.500, CCC will...

7 CFR 1493.30 - Information required for program participation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.30 Information required for program participation. Before CCC will accept an application...

7 CFR 1493.450 - Payment guarantee.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.450 Payment guarantee. (a) CCC's obligation. The payment guarantee will provide that CCC agrees to pay the exporter or the exporter's assignee an amount not to exceed the guaranteed...

7 CFR 1493.470 - Evidence of export.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... provide CCC an evidence of export report for each shipment made under the payment guarantee. This report... participation in any of the following CCC or USDA export program: Export Enhancement Program, Dairy Export...

7 CFR 1493.400 - General statement.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... forth at subpart A for the Commodity Credit Corporation (CCC) Export Credit Guarantee Program (GSM-102... CCC's guarantee. The program is operated in a manner intended not to interfere with markets for cash...

7 CFR 1493.100 - Proof of entry.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.100 Proof of entry... translation acceptable to CCC. Records acceptable to meet this requirement include an original certification...

7 CFR 1493.120 - Payment for loss.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.120 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of the information and...

7 CFR 1493.10 - General statement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... (GSM-103). The GSM-102 and GSM-103 programs of the Commodity Credit Corporation (CCC) were developed to...

7 CFR 1493.100 - Proof of entry.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.100 Proof of entry... translation acceptable to CCC. Records acceptable to meet this requirement include an original certification...

7 CFR 1493.40 - Application for payment guarantee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program..., contract loading tolerance and, if necessary, a request for CCC to reserve coverage up to the maximum...

7 CFR 1493.400 - General statement.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... forth at subpart A for the Commodity Credit Corporation (CCC) Export Credit Guarantee Program (GSM-102... CCC's guarantee. The program is operated in a manner intended not to interfere with markets for cash...

7 CFR 1493.290 - Proof of entry.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee... accompanied by a certified or other translation acceptable to CCC. Records acceptable to meet this requirement... documentation deemed acceptable by CCC: (i) Showing that the goods entered the emerging market; (ii) Identifying...

7 CFR 1493.260 - Facility payment guarantee.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.260 Facility payment guarantee. (a) CCC's maximum obligation. CCC will agree to pay the exporter or the exporter's assignee an amount not to exceed the...

7 CFR 1493.130 - Recovery of losses.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.130 Recovery of losses. (a) Notification. Upon payment of loss to the exporter or the exporter's assignee, CCC...

7 CFR 1493.310 - Payment for loss.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.310 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of the information and documents required under § 1493.300, CCC will determine whether or...

7 CFR 1493.10 - General statement.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.10... GSM-102 and GSM-103 programs of the Commodity Credit Corporation (CCC) were developed to expand U.S...

7 CFR 1493.10 - General statement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... (GSM-103). The GSM-102 and GSM-103 programs of the Commodity Credit Corporation (CCC) were developed to...

7 CFR 1493.510 - Payment for loss.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.510 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of the information and documents required under § 1493.500, CCC will...

7 CFR 1493.310 - Payment for loss.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.310 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of the information and documents required under § 1493.300, CCC will...

7 CFR 1493.10 - General statement.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.10... GSM-102 and GSM-103 programs of the Commodity Credit Corporation (CCC) were developed to expand U.S...

7 CFR 1493.130 - Recovery of losses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.130 Recovery of losses. (a) Notification. Upon payment of loss to the exporter or the exporter's assignee, CCC...

7 CFR 1493.30 - Information required for program participation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.30 Information required for program participation. Before CCC will accept an application...

7 CFR 1493.120 - Payment for loss.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.120 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of the information and...

7 CFR 1493.400 - General statement.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... forth at subpart A for the Commodity Credit Corporation (CCC) Export Credit Guarantee Program (GSM-102... CCC's guarantee. The program is operated in a manner intended not to interfere with markets for cash...

7 CFR 1493.100 - Proof of entry.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.100 Proof of entry... translation acceptable to CCC. Records acceptable to meet this requirement include an original certification...

7 CFR 1493.30 - Information required for program participation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.30 Information required for program participation. Before CCC will accept an application...

7 CFR 1493.310 - Payment for loss.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.310 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of the information and documents required under § 1493.300, CCC will determine whether or...

Atomic, Molecular, and Optical Physics: Optical Excitation Function of H(1s-2p) Produced by electron Impact from Threshold to 1.8 keV

NASA Technical Reports Server (NTRS)

James, G. K.; Slevin, J. A.; Shemansky, D. E.; McConkey, J. W.; Bray, I.; Dziczek, D.; Kanik, I.; Ajello, J. M.

1997-01-01

The optical excitation function of prompt Lyman-Alpha radiation, produced by electron impact on atomic hydrogen, has been measured over the extended energy range from threshold to 1.8 keV. Measurements were obtained in a crossed-beams experiment using both magnetically confined and electrostatically focused electrons in collision with atomic hydrogen produced by an intense discharge source. A vacuum-ultraviolet mono- chromator system was used to measure the emitted Lyman-Alpha radiation. The absolute H(1s-2p) electron impact excitation cross section was obtained from the experimental optical excitation function by normalizing to the accepted optical oscillator strength, with corrections for polarization and cascade. Statistical and known systematic uncertainties in our data range from +/- 4% near threshold to +/- 2% at 1.8 keV. Multistate coupling affecting the shape of the excitation function up to 1 keV impact energy is apparent in both the present experimental data and present theoretical results obtained with convergent close- coupling (CCC) theory. This shape function effect leads to an uncertainty in absolute cross sections at the 10% level in the analysis of the experimental data. The derived optimized absolute cross sections are within 7% of the CCC calculations over the 14 eV-1.8 keV range. The present CCC calculations converge on the Bethe- Fano profile for H(1s-2p) excitation at high energy. For this reason agreement with the CCC values to within 3% is achieved in a nonoptimal normalization of the experimental data to the Bethe-Fano profile. The fundamental H(1s-2p) electron impact cross section is thereby determined to an unprecedented accuracy over the 14 eV - 1.8 keV energy range.

Further understanding on the mechanism of alkyl ketene dimer sizing on the causticized calcium carbonate filled paper and its improvements.

PubMed

Wang, Jian; Dang, Miao; Duan, Chao; Qian, Li

2017-02-01

Causticized calcium carbonate (CCC), a solid waste derived from kraft black recovery process, can be used as an alternative for the conventional precipitated calcium carbonate (PCC). However, the application of the CCC has been limited due to its low sizing efficiency in its filled paper. In this study, the characteristics of the CCC were studied aiming to improve the alkyl ketene dimer (AKD) sizing performances of the CCC filled papers, and the results were compared with those from PCC filled papers. The results showed that the CCC had higher pore structure, higher specific surface area, and more negative charge density than the PCC, thus leading to a higher cationic AKD adsorption onto the CCC filler. The lower AKD sizing efficiency in the CCC filled paper can be explained by the combination of higher AKD adsorption and migration, both of which resulted in preferred AKD adsorption onto/into the CCC fillers, rather than the cellulose fibers. Based on the above, the prior addition of polyamide-polyamine epichlorhydrin (PAE) resin to the CCC filler system was proposed to remedy the related issues, thus improving the sizing efficiency.

7 CFR 1493.280 - Evidence of export report.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... to provide CCC an evidence of export report for each shipment of goods or provision of services... provided were included in the final application for a final commitment as approved by CCC for coverage...

7 CFR 1493.210 - Definition of terms.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... given, has obtained the legal rights to receive payment under the facility payment guarantee. CCC. The... facsimile numbers of contacts within FAS/USDA and CCC. The Contacts P/R also contains details about where to...

7 CFR 1493.210 - Definition of terms.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... given, has obtained the legal rights to receive payment under the facility payment guarantee. CCC. The... facsimile numbers of contacts within FAS/USDA and CCC. The Contacts P/R also contains details about where to...

7 CFR 1493.140 - Miscellaneous provisions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.140..., payable by CCC under a payment guarantee or the right to such proceeds only to a financial institution in...

7 CFR 1493.510 - Payment for loss.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.510 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of the information and documents required under § 1493.500, CCC will determine whether or not a...

7 CFR 1493.420 - Information required for program participation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC.... Before CCC will accept an application for a payment guarantee under the SCGP, the applicant must qualify... publicly available sources, CCC will determine whether the applicant is eligible for participation in the...

7 CFR 1493.270 - Certifications.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP... submitted to CCC under this subpart, is the exporter's certification that: (1) There have not been and are... amended, or other U.S. Laws; (2) All information submitted to CCC is true and correct; and (3) The...

7 CFR 1488.3 - General.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Financing Export Sales § 1488.3 General. When considering the extension of CCC credit for the purpose of financing agricultural commodities, CCC will take into account the extent to which CCC credit financing will...

7 CFR 1493.80 - Evidence of export.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.80 Evidence of export. (a) Report of export. The exporter is required to provide CCC an evidence of export...

7 CFR 1493.40 - Application for payment guarantee.

Code of Federal Regulations, 2012 CFR

2012-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493..., if necessary, a request for CCC to reserve coverage up to the maximum quantity permitted by the...

7 CFR 1493.510 - Payment for loss.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.510 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of the information and documents required under § 1493.500, CCC will determine whether or not a...

7 CFR 1493.470 - Evidence of export.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... exporter is required to provide CCC an evidence of export report for each shipment made under the payment... participation in any of the following CCC or USDA export program: Export Enhancement Program, Dairy Export...

7 CFR 1493.270 - Certifications.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP... submitted to CCC under this subpart, is the exporter's certification that: (1) There have not been and are... amended, or other U.S. Laws; (2) All information submitted to CCC is true and correct; and (3) The...

7 CFR 1493.420 - Information required for program participation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC.... Before CCC will accept an application for a payment guarantee under the SCGP, the applicant must qualify... publicly available sources, CCC will determine whether the applicant is eligible for participation in the...

7 CFR 1493.140 - Miscellaneous provisions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.140..., payable by CCC under a payment guarantee or the right to such proceeds only to a financial institution in...

7 CFR 1493.270 - Certifications.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee... documentation submitted to CCC under this subpart, is the exporter's certification that: (1) There have not been... amended, or other U.S. Laws; (2) All information submitted to CCC is true and correct; and (3) The...

7 CFR 1493.80 - Evidence of export.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.80 Evidence of export. (a) Report of export. The exporter is required to provide CCC an...

7 CFR 1493.280 - Evidence of export report.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... to provide CCC an evidence of export report for each shipment of goods or provision of services... provided were included in the final application for a final commitment as approved by CCC for coverage...

7 CFR 1493.210 - Definition of terms.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... given, has obtained the legal rights to receive payment under the facility payment guarantee. CCC. The... facsimile numbers of contacts within FAS/USDA and CCC. The Contacts P/R also contains details about where to...

7 CFR 1488.3 - General.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Financing Export Sales § 1488.3 General. When considering the extension of CCC credit for the purpose of financing agricultural commodities, CCC will take into account the extent to which CCC credit financing will: (a) Permit...

7 CFR 1493.40 - Application for payment guarantee.

Code of Federal Regulations, 2014 CFR

2014-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493..., if necessary, a request for CCC to reserve coverage up to the maximum quantity permitted by the...

7 CFR 1493.140 - Miscellaneous provisions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... which are, or may become, payable by CCC under a payment guarantee or the right to such proceeds only to...

7 CFR 1488.3 - General.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Financing Export Sales § 1488.3 General. When considering the extension of CCC credit for the purpose of financing agricultural commodities, CCC will take into account the extent to which CCC credit financing will...

7 CFR 1488.3 - General.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Financing Export Sales § 1488.3 General. When considering the extension of CCC credit for the purpose of financing agricultural commodities, CCC will take into account the extent to which CCC credit financing will: (a) Permit...

7 CFR 1493.80 - Evidence of export.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.80 Evidence of export. (a) Report of export. The exporter is required to provide CCC an evidence of export...

7 CFR 1493.280 - Evidence of export report.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... to provide CCC an evidence of export report for each shipment of goods or provision of services... provided were included in the final application for a final commitment as approved by CCC for coverage...

7 CFR 1493.140 - Miscellaneous provisions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... which are, or may become, payable by CCC under a payment guarantee or the right to such proceeds only to...

7 CFR 1488.3 - General.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Financing Export Sales § 1488.3 General. When considering the extension of CCC credit for the purpose of financing agricultural commodities, CCC will take into account the extent to which CCC credit financing will: (a) Permit...

7 CFR 1493.280 - Evidence of export report.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... exporter is required to provide CCC an evidence of export report for each shipment of goods or provision of... CCC for coverage under the facility payment guarantee and this subpart; (ii) The specifications and...

7 CFR 1493.270 - Certifications.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP... submitted to CCC under this subpart, is the exporter's certification that: (1) There have not been and are... amended, or other U.S. Laws; (2) All information submitted to CCC is true and correct; and (3) The...

7 CFR 1493.140 - Miscellaneous provisions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.140..., payable by CCC under a payment guarantee or the right to such proceeds only to a financial institution in...

7 CFR 1493.270 - Certifications.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee... documentation submitted to CCC under this subpart, is the exporter's certification that: (1) There have not been... amended, or other U.S. Laws; (2) All information submitted to CCC is true and correct; and (3) The...

7 CFR 1493.40 - Application for payment guarantee.

Code of Federal Regulations, 2013 CFR

2013-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493..., if necessary, a request for CCC to reserve coverage up to the maximum quantity permitted by the...

7 CFR 1493.510 - Payment for loss.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.510 Payment for loss. (a) Determination of CCC's liability. Upon receipt in good order of the information and documents required under § 1493.500, CCC will determine whether or not a...

7 CFR 1493.330 - Miscellaneous provisions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... exporter may assign the proceeds which are, or may become, payable by CCC under a facility payment... than one party, and may not, unless approved in advance by CCC, be subject to further assignment. Any...

7 CFR 1493.420 - Information required for program participation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC.... Before CCC will accept an application for a payment guarantee under the SCGP, the applicant must qualify... publicly available sources, CCC will determine whether the applicant is eligible for participation in the...

7 CFR 1493.80 - Evidence of export.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.80 Evidence of export. (a) Report of export. The exporter is required to provide CCC an evidence of export...

7 CFR 1493.330 - Miscellaneous provisions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... exporter may assign the proceeds which are, or may become, payable by CCC under a facility payment... than one party, and may not, unless approved in advance by CCC, be subject to further assignment. Any...

Phosphoregulation of the C. elegans cadherin–catenin complex

PubMed Central

Callaci, Sandhya; Morrison, Kylee; Shao, Xiangqiang; Schuh, Amber L.; Wang, Yueju; Yates, John R.; Hardin, Jeff; Audhya, Anjon

2015-01-01

Adherens junctions play key roles in mediating cell–cell contacts during tissue development. In Caenorhabditis elegans embryos, the cadherin–catenin complex (CCC), composed of the classical cadherin HMR-1 and members of three catenin families, HMP-1, HMP-2 and JAC-1, is necessary for normal blastomere adhesion, gastrulation, ventral enclosure of the epidermis and embryo elongation. Disruption of CCC assembly or function results in embryonic lethality. Previous work suggests that components of the CCC are subject to phosphorylation. However, the identity of phosphorylated residues in CCC components and their contributions to CCC stability and function in a living organism remain speculative. Using mass spectrometry, we systematically identify phosphorylated residues in the essential CCC subunits HMR-1, HMP-1 and HMP-2 in vivo. We demonstrate that HMR-1/cadherin phosphorylation occurs on three sites within its β-catenin binding domain that each contributes to CCC assembly on lipid bilayers. In contrast, phosphorylation of HMP-2/β-catenin inhibits its association with HMR-1/cadherin in vitro, suggesting a role in CCC disassembly. Although HMP-1/α-catenin is also phosphorylated in vivo, phosphomimetic mutations do not affect its ability to associate with other CCC components or interact with actin in vitro. Collectively, our findings support a model in which distinct phosphorylation events contribute to rapid CCC assembly and disassembly, both of which are essential for morphogenetic rearrangements during development. PMID:26443865

The Analysis of Cell Cycle-related Proteins in Ovarian Clear Cell Carcinoma Versus High-grade Serous Carcinoma.

PubMed

Hazama, Yukiko; Moriya, Takuya; Sugihara, Mika; Sano, Rikiya; Shiota, Mitsuru; Nakamura, Takafumi; Shimoya, Koichiro

2017-10-10

In Japan, the frequency of ovarian clear cell carcinoma (CCC) is twice as high as that in the United States and Europe. Often, patient prognosis of CCC is poor because of chemoresistance. Here, we focus on the cell cycle, which is one of the mechanisms of chemoresistance. To detect the informative markers and improve the strategy of chemotherapy for CCC, we performed immunochemical staining of cell cycle-related proteins in ovarian malignant tumors. We detected that each of the 29 samples of CCC and high-grade serous carcinoma (HGSC) were necessary to reveal the significant differences in immunostaining and prognosis. We performed the immunostaining analysis using the antibodies of cell cycle-related proteins such as Ki-67, Cdt1, MCM7, and geminin. The positive rate of Cdt1 in the CCC group was significantly higher than that in the HGSC group (P<0.0001). However, the positive rate of geminin in the HGSC group was significantly higher than that in the CCC group (P<0.0001). The overall survival of CCC patients with high labeling index of Cdt1 was significantly worse than that of CCC patients with low labeling index of Cdt1 (P=0.004). The study results suggested that the cancer cells of CCC and HGSC exist in the G1 phase and S, G2, and M phases, respectively. The differences in cell cycle of CCC might be one of the reasons for chemotherapy resistance. Further investigations are necessary to reveal the usefulness of Cdt1 as a biomarker in CCC.

7 CFR 1494.201 - Definitions of terms.

Code of Federal Regulations, 2010 CFR

2010-01-01

... offer, if applicable. (b) Announced CCC bonus—A CCC bonus announced by CCC by public press release in... shipped from a Canadian transshipment port on the St. Lawrence River, provided its identity had been... of Agriculture, acting in the capacity of Vice President, CCC, or the GSM's designee. (w) Invitation...

7 CFR 1494.201 - Definitions of terms.

Code of Federal Regulations, 2011 CFR

2011-01-01

... offer, if applicable. (b) Announced CCC bonus—A CCC bonus announced by CCC by public press release in... shipped from a Canadian transshipment port on the St. Lawrence River, provided its identity had been... of Agriculture, acting in the capacity of Vice President, CCC, or the GSM's designee. (w) Invitation...

78 FR 45441 - Sugar Program; Feedstock Flexibility Program for Bioenergy Producers

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-29

... sugarcane processors may borrow from CCC, pledging their sugar production as collateral for any such loan... sugar for bioenergy production under FFP as a proactive means for CCC to avoid forfeitures. FFP is... production. In addition, CCC will make quarterly announcements of revised estimates of such quantity. CCC's...

7 CFR 1427.1088 - Contract fees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... storage and handling of CCC-owned cotton or cotton pledged to CCC as loan collateral must pay an annual... storage and handling of CCC-owned cotton or cotton pledged to CCC as loan collateral but who desires such... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS COTTON Standards for Approval of Warehouses for...

7 CFR 1493.330 - Miscellaneous provisions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... proceeds which are, or may become, payable by CCC under a facility payment guarantee or the right to such..., unless approved in advance by CCC, be subject to further assignment. Any assignment may be made to one...

7 CFR 1402.5 - Late payments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... payments. If payment is not received by CCC within the period specified in the sales contract, interest will be assessed by CCC. If a buyer fails to make arrangements for payment according to the provisions of the contract, CCC retains the right to terminate the sales contract. If CCC terminates the sales...

50 CFR 600.117 - Council coordination committee (CCC).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Council coordination committee (CCC). 600... Councils § 600.117 Council coordination committee (CCC). (a) The Councils may establish a Council coordination committee (CCC) consisting of the chairs, vice chairs, and executive directors of each of the...

7 CFR 1493.90 - Certification requirements for the evidence of export.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit... breaches or violates these certifications with respect to a GSM-102 or GSM-103 payment guarantee, CCC will...

50 CFR 600.117 - Council coordination committee (CCC).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Council coordination committee (CCC). 600... Councils § 600.117 Council coordination committee (CCC). (a) The Councils may establish a Council coordination committee (CCC) consisting of the chairs, vice chairs, and executive directors of each of the...

76 FR 57940 - CCC Export Credit Guarantee (GSM-102) Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

... Corporation 7 CFR Part 1493 RIN 0551-AA74 CCC Export Credit Guarantee (GSM-102) Program AGENCY: Foreign.... SUMMARY: The Commodity Credit Corporation (CCC) published a proposed rule on July 27, 2011 (76 FR 44836..., and include other administrative revisions to enhance clarity and program integrity. CCC is extending...

7 CFR 1493.530 - Miscellaneous provisions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... exporter may assign the proceeds which are, or may become, payable by CCC under a payment guarantee or the..., unless approved in advance by CCC, be: (i) Made to one party acting for two or more parties; or (ii...

7 CFR 1493.70 - Guarantee rates and fees.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.70... length of the payment terms provided for in the export sale contract, the degree of risk that CCC assumes...

7 CFR 1493.110 - Notice of default and claims for loss.

Code of Federal Regulations, 2013 CFR

2013-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493... related obligation, the exporter or the exporter's assignee must submit a notice of default to CCC as soon...

7 CFR 1493.90 - Certification requirements for the evidence of export.

Code of Federal Regulations, 2014 CFR

2014-01-01

... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... certifications with respect to a GSM-102 or GSM-103 payment guarantee, CCC will have the right, notwithstanding...

7 CFR 1488.18 - Covenant against contingent fees.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURAL COMMODITIES Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC..., CCC shall have the right, without limitation on any other rights it may have, to annul the financing agreement without liability to CCC. Should the financing agreement be annulled, CCC will promptly consent to...

7 CFR 1405.4 - Delegations of authority.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Delegations of authority. The delegations of authority relating to the CCC programs and activities are set forth in the by-laws of CCC and in dockets approved by the CCC Board of Directors. Copies of the By-laws and the dockets may be obtained from the Secretary of CCC. ...

77 FR 6533 - Information Collection Request; Assignment and Joint Payment Elections

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-08

... Act of 1995, the Commodity Credit Corporation (CCC) and Farm Service Agency (FSA) are seeking comments... assign a cash payment made by FSA or CCC to a third party. In addition, a payment recipient may...). SUPPLEMENTARY INFORMATION: Title: CCC-36, ``Assignment of Payment'', CCC-37, ``Joint Payment Authorization...

7 CFR 1488.18 - Covenant against contingent fees.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales... exporter for the purpose of securing business. For breach or violation of this warranty, CCC shall have the... liability to CCC. Should the financing agreement be annulled, CCC will promptly consent to the reduction or...

7 CFR 1493.110 - Notice of default and claims for loss.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program... default to CCC as soon as possible, but not later than 10 calendar days after the date that payment was...

7 CFR 1493.110 - Notice of default and claims for loss.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program... default to CCC as soon as possible, but not later than 10 calendar days after the date that payment was...

50 CFR 600.117 - Council coordination committee (CCC).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Council coordination committee (CCC). 600... Councils § 600.117 Council coordination committee (CCC). (a) The Councils may establish a Council coordination committee (CCC) consisting of the chairs, vice chairs, and executive directors of each of the...

7 CFR 1493.430 - Application for a payment guarantee.

Code of Federal Regulations, 2013 CFR

2013-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier... quantity, contract loading tolerance and, if the exporter chooses, a request for CCC to reserve coverage up... is also being used as the basis for an application for participation in any of the following CCC or...

7 CFR 1488.18 - Covenant against contingent fees.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales... exporter for the purpose of securing business. For breach or violation of this warranty, CCC shall have the... liability to CCC. Should the financing agreement be annulled, CCC will promptly consent to the reduction or...

7 CFR 1493.50 - Certification requirements for obtaining payment guarantee.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export... notify CCC if there is a change of circumstances which would cause it to fail to meet such requirements...

7 CFR 1493.460 - Guarantee rates and fees.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... not be approved until the guarantee fee has been received by CCC. The exporter's check for the guarantee fee shall be made payable to CCC and mailed or delivered by courier to the office specified in the...

7 CFR 1488.18 - Covenant against contingent fees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURAL COMMODITIES Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC..., CCC shall have the right, without limitation on any other rights it may have, to annul the financing agreement without liability to CCC. Should the financing agreement be annulled, CCC will promptly consent to...

7 CFR 1493.530 - Miscellaneous provisions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... proceeds which are, or may become, payable by CCC under a payment guarantee or the right to such proceeds... in advance by CCC, be: (i) Made to one party acting for two or more parties; or (ii) Subject to...

7 CFR 1493.110 - Notice of default and claims for loss.

Code of Federal Regulations, 2012 CFR

2012-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493... related obligation, the exporter or the exporter's assignee must submit a notice of default to CCC as soon...

7 CFR 1488.5 - Acceptance of sale registrations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... COMMODITIES Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit... and eligible for financing. (b) [Reserved] (c) CCC reserves the right to reject any and all requests... exporter and CCC which shall consist of the exporter's request for a sale registration, CCC's acceptance of...

7 CFR 1493.70 - Guarantee rates and fees.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.70... length of the payment terms provided for in the export sale contract, the degree of risk that CCC assumes...

7 CFR 1493.90 - Certification requirements for the evidence of export.

Code of Federal Regulations, 2012 CFR

2012-01-01

... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... certifications with respect to a GSM-102 or GSM-103 payment guarantee, CCC will have the right, notwithstanding...

7 CFR 1493.460 - Guarantee rates and fees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... the guarantee fee. Applications will not be approved until the guarantee fee has been received by CCC. The exporter's check for the guarantee fee shall be made payable to CCC and mailed or delivered by...

7 CFR 1493.90 - Certification requirements for the evidence of export.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit... breaches or violates these certifications with respect to a GSM-102 or GSM-103 payment guarantee, CCC will...

7 CFR 1493.330 - Miscellaneous provisions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... proceeds which are, or may become, payable by CCC under a facility payment guarantee or the right to such..., unless approved in advance by CCC, be subject to further assignment. Any assignment may be made to one...

7 CFR 1485.18 - Reimbursement procedures.

Code of Federal Regulations, 2014 CFR

2014-01-01

... required to use CCC's Internet-based UES system to request reimbursement for eligible MAP expenses. Claims... reimbursed; (7) If applicable, any reduction in the amount of reimbursement claimed to offset CCC demand for... reimbursement shall be submitted by the MAP Participant's U.S. office to CCC. (c) CCC will not reimburse a claim...

7 CFR 1405.4 - Delegations of authority.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Delegations of authority. The delegations of authority relating to the CCC programs and activities are set forth in the by-laws of CCC and in dockets approved by the CCC Board of Directors. Copies of the By-laws and the dockets may be obtained from the Secretary of CCC. ...

7 CFR 1493.460 - Guarantee rates and fees.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... the guarantee fee. Applications will not be approved until the guarantee fee has been received by CCC. The exporter's check for the guarantee fee shall be made payable to CCC and mailed or delivered by...

50 CFR 600.117 - Council coordination committee (CCC).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Council coordination committee (CCC). 600... Councils § 600.117 Council coordination committee (CCC). (a) The Councils may establish a Council coordination committee (CCC) consisting of the chairs, vice chairs, and executive directors of each of the...

7 CFR 1402.5 - Late payments.

Code of Federal Regulations, 2012 CFR

2012-01-01

... payments. If payment is not received by CCC within the period specified in the sales contract, interest will be assessed by CCC. If a buyer fails to make arrangements for payment according to the provisions of the contract, CCC retains the right to terminate the sales contract. If CCC terminates the sales...

7 CFR 1493.50 - Certification requirements for obtaining payment guarantee.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export... notify CCC if there is a change of circumstances which would cause it to fail to meet such requirements...

76 FR 14370 - Information Collection; Representation for CCC and FSA Loans Authorization To File a Financing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

...; Representation for CCC and FSA Loans Authorization To File a Financing Statement AGENCY: Commodity Credit... the Paperwork Reduction Act of 1995, the Commodity Credit Corporation (CCC) and the Farm Service... currently approved information collection associated with form CCC-10, entitled ``Representations for...

7 CFR 1485.18 - Reimbursement procedures.

Code of Federal Regulations, 2013 CFR

2013-01-01

... required to use CCC's Internet-based UES system to request reimbursement for eligible MAP expenses. Claims... reimbursed; (7) If applicable, any reduction in the amount of reimbursement claimed to offset CCC demand for... reimbursement shall be submitted by the MAP Participant's U.S. office to CCC. (c) CCC will not reimburse a claim...

7 CFR 1402.5 - Late payments.

Code of Federal Regulations, 2013 CFR

2013-01-01

... payments. If payment is not received by CCC within the period specified in the sales contract, interest will be assessed by CCC. If a buyer fails to make arrangements for payment according to the provisions of the contract, CCC retains the right to terminate the sales contract. If CCC terminates the sales...

7 CFR 1493.530 - Miscellaneous provisions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... proceeds which are, or may become, payable by CCC under a payment guarantee or the right to such proceeds... in advance by CCC, be: (i) Made to one party acting for two or more parties; or (ii) Subject to...

7 CFR 1493.330 - Miscellaneous provisions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program... proceeds which are, or may become, payable by CCC under a facility payment guarantee or the right to such..., unless approved in advance by CCC, be subject to further assignment. Any assignment may be made to one...

7 CFR 1405.4 - Delegations of authority.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Delegations of authority. The delegations of authority relating to the CCC programs and activities are set forth in the by-laws of CCC and in dockets approved by the CCC Board of Directors. Copies of the By-laws and the dockets may be obtained from the Secretary of CCC. ...

7 CFR 1493.50 - Certification requirements for obtaining payment guarantee.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program... requirements of § 1493.30, and the exporter will immediately notify CCC if there is a change of circumstances...

7 CFR 1402.5 - Late payments.

Code of Federal Regulations, 2011 CFR

2011-01-01

... payments. If payment is not received by CCC within the period specified in the sales contract, interest will be assessed by CCC. If a buyer fails to make arrangements for payment according to the provisions of the contract, CCC retains the right to terminate the sales contract. If CCC terminates the sales...

7 CFR 1488.5 - Acceptance of sale registrations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... COMMODITIES Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit... and eligible for financing. (b) [Reserved] (c) CCC reserves the right to reject any and all requests... exporter and CCC which shall consist of the exporter's request for a sale registration, CCC's acceptance of...

7 CFR 1488.18 - Covenant against contingent fees.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales... exporter for the purpose of securing business. For breach or violation of this warranty, CCC shall have the... liability to CCC. Should the financing agreement be annulled, CCC will promptly consent to the reduction or...

7 CFR 1493.530 - Miscellaneous provisions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... proceeds which are, or may become, payable by CCC under a payment guarantee or the right to such proceeds... in advance by CCC, be: (i) Made to one party acting for two or more parties; or (ii) Subject to...

7 CFR 1493.430 - Application for a payment guarantee.

Code of Federal Regulations, 2014 CFR

2014-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier... quantity, contract loading tolerance and, if the exporter chooses, a request for CCC to reserve coverage up... is also being used as the basis for an application for participation in any of the following CCC or...

7 CFR 1493.530 - Miscellaneous provisions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... exporter may assign the proceeds which are, or may become, payable by CCC under a payment guarantee or the..., unless approved in advance by CCC, be: (i) Made to one party acting for two or more parties; or (ii...

7 CFR 1402.5 - Late payments.

Code of Federal Regulations, 2014 CFR

2014-01-01

... payments. If payment is not received by CCC within the period specified in the sales contract, interest will be assessed by CCC. If a buyer fails to make arrangements for payment according to the provisions of the contract, CCC retains the right to terminate the sales contract. If CCC terminates the sales...

7 CFR 1493.460 - Guarantee rates and fees.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... not be approved until the guarantee fee has been received by CCC. The exporter's check for the guarantee fee shall be made payable to CCC and mailed or delivered by courier to the office specified in the...

7 CFR 1493.460 - Guarantee rates and fees.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... not be approved until the guarantee fee has been received by CCC. The exporter's check for the guarantee fee shall be made payable to CCC and mailed or delivered by courier to the office specified in the...

7 CFR 1435.605 - Competitive procedures.

Code of Federal Regulations, 2014 CFR

2014-01-01

... § 1435.605 Competitive procedures. (a) CCC will generally issue tenders for bids, before entering into... the least cost to CCC of removing sugar from the market. (b) CCC may, at times, negotiate contracts directly with sellers or buyers, if CCC determines that such negotiation will result in either reduced...

7 CFR 1493.50 - Certification requirements for obtaining payment guarantee.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program... requirements of § 1493.30, and the exporter will immediately notify CCC if there is a change of circumstances...

7 CFR 1493.70 - Guarantee rates and fees.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.70... length of the payment terms provided for in the export sale contract, the degree of risk that CCC assumes...

7 CFR 1405.4 - Delegations of authority.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Delegations of authority. The delegations of authority relating to the CCC programs and activities are set forth in the by-laws of CCC and in dockets approved by the CCC Board of Directors. Copies of the By-laws and the dockets may be obtained from the Secretary of CCC. ...

7 CFR 1493.430 - Application for a payment guarantee.

Code of Federal Regulations, 2012 CFR

2012-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier... quantity, contract loading tolerance and, if the exporter chooses, a request for CCC to reserve coverage up... is also being used as the basis for an application for participation in any of the following CCC or...

7 CFR 1493.50 - Certification requirements for obtaining payment guarantee.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program... requirements of § 1493.30, and the exporter will immediately notify CCC if there is a change of circumstances...

50 CFR 600.117 - Council coordination committee (CCC).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Council coordination committee (CCC). 600... Councils § 600.117 Council coordination committee (CCC). (a) The Councils may establish a Council coordination committee (CCC) consisting of the chairs, vice chairs, and executive directors of each of the...

7 CFR 1493.90 - Certification requirements for the evidence of export.

Code of Federal Regulations, 2013 CFR

2013-01-01

... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... certifications with respect to a GSM-102 or GSM-103 payment guarantee, CCC will have the right, notwithstanding...

7 CFR 1405.4 - Delegations of authority.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Delegations of authority. The delegations of authority relating to the CCC programs and activities are set forth in the by-laws of CCC and in dockets approved by the CCC Board of Directors. Copies of the By-laws and the dockets may be obtained from the Secretary of CCC. ...

7 CFR 1493.110 - Notice of default and claims for loss.

Code of Federal Regulations, 2014 CFR

2014-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493... related obligation, the exporter or the exporter's assignee must submit a notice of default to CCC as soon...

Transmetallation from CCC-NHC pincer Zr complexes in the synthesis of air-stable CCC-NHC pincer Co(iii) complexes and initial hydroboration trials.

PubMed

Reilly, Sean W; Webster, Charles Edwin; Hollis, T Keith; Valle, Henry U

2016-02-21

Development of CCC-NHC pincer Co complexes via transmetalation from Zr is reported. Formation of these air-stable Co(iii) complexes was achieved through use of a CoCl2 or Co(acac)3in situ or with a discrete CCC-NHC pincer Zr transmetallating agent. Preliminary activity in the hydroboration of styrene is reported. This facile methodology will further the development of CCC-NHC pincer first-row transition metal complexes.

Ankle Injury Management (AIM): design of a pragmatic multi-centre equivalence randomised controlled trial comparing Close Contact Casting (CCC) to Open surgical Reduction and Internal Fixation (ORIF) in the treatment of unstable ankle fractures in patients over 60 years

PubMed Central

2014-01-01

Background Ankle fractures account for 9% of all fractures with a quarter of these occurring in adults over 60 years. The short term disability and long-term consequences of this injury can be considerable. Current opinion favours open reduction and internal fixation (ORIF) over non-operative treatment (fracture manipulation and the application of a standard moulded cast) for older people. Both techniques are associated with complications but the limited published research indicates higher complication rates of fracture malunion (poor position at healing) with casting. The aim of this study is to compare ORIF with a modification of existing casting techniques, Close Contact Casting (CCC). We propose that CCC may offer an equivalent functional outcome to ORIF and avoid the risks associated with surgery. Methods/Design This study is a pragmatic multi-centre equivalence randomised controlled trial. 620 participants will be randomised to receive ORIF or CCC after sustaining an isolated displaced unstable ankle fracture. Participants will be recruited from a minimum of 20 National Health Service (NHS) acute hospitals throughout England and Wales. Participants will be aged over 60 years and be ambulatory prior to injury. Follow-up will be at six weeks and six months after randomisation. The primary outcome is the Olerud & Molander Ankle Score, a functional patient reported outcome measure, at 6 months. Follow-up will also include assessments of mobility, ankle range of movement, health related quality of life and complications. The six-month follow-up will be conducted face-to-face by an assessor blinded to the allocated intervention. A parallel economic evaluation will consider both a health service and a broader societal perspective including the individual and their family. In order to explore patient experience of their treatment and recovery, a purposive sample of 40 patients will also be interviewed using a semi-structured interview schedule between 6-10 weeks post treatment. Discussion This multicentre study was open to recruitment July 2010 and recruitment is due to be completed in December 2013. Trial registration Current Controlled Trials ISRCTN04180738. PMID:24621174

78 FR 59289 - Clarification of Bales Made Available for Shipment by CCC-Approved Warehouses

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-26

... for CCC-approved warehouses storing cotton. The amendment would change the definition of Bales Made Available for Shipment (BMAS). CCC-approved cotton warehouses are currently required to report BMAS, among... information about bales available for shipment, benefiting both CCC and the cotton industry. DATES: We will...

7 CFR 1435.602 - Eligible sugar to be purchased by CCC.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Eligible sugar to be purchased by CCC. 1435.602... CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS SUGAR PROGRAM Feedstock Flexibility Program § 1435.602 Eligible sugar to be purchased by CCC. (a) CCC will only purchase raw sugar...

7 CFR 1427.21 - Settlement.

Code of Federal Regulations, 2013 CFR

2013-01-01

... § 1427.21 Settlement. (a) The settlement of cotton loans will be made by CCC on the basis of the quality and quantity of the cotton delivered to CCC by the producer or acquired by CCC subject to the producer... maximum storage credit rates as determined and announced by CCC. (b) For purposes of settlements for...

7 CFR 1488.12 - Coverage of bank obligations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Bank... when determined by the President or Vice President, CCC after consultation with the Controller, CCC, to be in the interest of CCC. (c) A U.S. bank must confirm the full amount of an obligation issued by...

7 CFR 1494.501 - Submission of offers to CCC.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Submission of offers to CCC. 1494.501 Section 1494... Program Operations § 1494.501 Submission of offers to CCC. (a) Consideration of offers. Unless otherwise specified in the Invitation, CCC will consider offers on a daily basis from the date of issuance of the...

7 CFR 17.9 - CCC payment to suppliers.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 1 2013-01-01 2013-01-01 false CCC payment to suppliers. 17.9 Section 17.9... TITLE I OF THE AGRICULTURAL TRADE DEVELOPMENT AND ASSISTANCE ACT OF 1954, AS AMENDED § 17.9 CCC payment to suppliers. (a) General. (1) The supplier shall request payment from CCC for the amount of the...

7 CFR 1488.12 - Coverage of bank obligations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales... be confirmed by an agency bank when determined by the President or Vice President, CCC after consultation with the Controller, CCC, to be in the interest of CCC. (c) A U.S. bank must confirm the full...

7 CFR 1494.501 - Submission of offers to CCC.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Submission of offers to CCC. 1494.501 Section 1494....501 Submission of offers to CCC. (a) Consideration of offers. Unless otherwise specified in the Invitation, CCC will consider offers on a daily basis from the date of issuance of the Invitation until such...

7 CFR 1493.500 - Notice of default and claims for loss.

Code of Federal Regulations, 2014 CFR

2014-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier... exporter or the exporter's assignee must submit a notice of default to CCC as soon as possible, but not... notice of default must be submitted in writing to the Treasurer, CCC, at the address specified in the...

7 CFR 1962.19 - Claims against Commodity Credit Corporation (CCC).

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 14 2013-01-01 2013-01-01 false Claims against Commodity Credit Corporation (CCC... Liquidation of Chattel Security § 1962.19 Claims against Commodity Credit Corporation (CCC). This section is based on a Memorandum of Understanding between CCC and FmHA or its successor agency under Public Law 103...

7 CFR 1493.300 - Notice of default and claims for loss.

Code of Federal Regulations, 2013 CFR

2013-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility... notice of default to CCC as soon as possible, but not later than ten days after the date that payment was... Treasurer, CCC, at the address specified in the Contacts P/R. If the exporter or the exporter's assignee...

7 CFR 1493.500 - Notice of default and claims for loss.

Code of Federal Regulations, 2012 CFR

2012-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier... exporter or the exporter's assignee must submit a notice of default to CCC as soon as possible, but not... notice of default must be submitted in writing to the Treasurer, CCC, at the address specified in the...

7 CFR 1493.300 - Notice of default and claims for loss.

Code of Federal Regulations, 2014 CFR

2014-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility... notice of default to CCC as soon as possible, but not later than ten days after the date that payment was... Treasurer, CCC, at the address specified in the Contacts P/R. If the exporter or the exporter's assignee...

7 CFR 1405.1 - Interest.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) Except as may otherwise be determined by CCC as provided in individual program regulations, program contracts or such other means as deemed appropriate by CCC the rate of interest that is applicable to CCC loans shall be equal to the rate of interest charged by the U.S. Treasury for funds borrowed by CCC on...

7 CFR 1403.8 - Withholding.

Code of Federal Regulations, 2013 CFR

2013-01-01

... payable to a debtor by CCC to ensure that the interests of CCC and the United States will be protected as provided in this section. (b) A payment may be withheld to protect the interests of CCC or the United States only if CCC determines that: (1) There has been a serious breach of contract or violation of...

7 CFR 1488.12 - Coverage of bank obligations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales... be confirmed by an agency bank when determined by the President or Vice President, CCC after consultation with the Controller, CCC, to be in the interest of CCC. (c) A U.S. bank must confirm the full...

7 CFR 1493.500 - Notice of default and claims for loss.

Code of Federal Regulations, 2013 CFR

2013-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier... exporter or the exporter's assignee must submit a notice of default to CCC as soon as possible, but not... notice of default must be submitted in writing to the Treasurer, CCC, at the address specified in the...

7 CFR 17.9 - CCC payment to suppliers.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 1 2011-01-01 2011-01-01 false CCC payment to suppliers. 17.9 Section 17.9... TITLE I OF THE AGRICULTURAL TRADE DEVELOPMENT AND ASSISTANCE ACT OF 1954, AS AMENDED § 17.9 CCC payment to suppliers. (a) General. (1) The supplier shall request payment from CCC for the amount of the...

7 CFR 17.9 - CCC payment to suppliers.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 1 2012-01-01 2012-01-01 false CCC payment to suppliers. 17.9 Section 17.9... TITLE I OF THE AGRICULTURAL TRADE DEVELOPMENT AND ASSISTANCE ACT OF 1954, AS AMENDED § 17.9 CCC payment to suppliers. (a) General. (1) The supplier shall request payment from CCC for the amount of the...

7 CFR 1962.19 - Claims against Commodity Credit Corporation (CCC).

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 14 2014-01-01 2014-01-01 false Claims against Commodity Credit Corporation (CCC... Liquidation of Chattel Security § 1962.19 Claims against Commodity Credit Corporation (CCC). This section is based on a Memorandum of Understanding between CCC and FmHA or its successor agency under Public Law 103...

7 CFR 1405.1 - Interest.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) Except as may otherwise be determined by CCC as provided in individual program regulations, program contracts or such other means as deemed appropriate by CCC the rate of interest that is applicable to CCC loans shall be equal to the rate of interest charged by the U.S. Treasury for funds borrowed by CCC on...

7 CFR 1962.19 - Claims against Commodity Credit Corporation (CCC).

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 14 2012-01-01 2012-01-01 false Claims against Commodity Credit Corporation (CCC... Liquidation of Chattel Security § 1962.19 Claims against Commodity Credit Corporation (CCC). This section is based on a Memorandum of Understanding between CCC and FmHA or its successor agency under Public Law 103...

7 CFR 1427.21 - Settlement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... § 1427.21 Settlement. (a) The settlement of cotton loans will be made by CCC on the basis of the quality and quantity of the cotton delivered to CCC by the producer or acquired by CCC subject to the producer... maximum storage credit rates as determined and announced by CCC. (b) For purposes of settlements for...

7 CFR 1494.501 - Submission of offers to CCC.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Submission of offers to CCC. 1494.501 Section 1494....501 Submission of offers to CCC. (a) Consideration of offers. Unless otherwise specified in the Invitation, CCC will consider offers on a daily basis from the date of issuance of the Invitation until such...

7 CFR 1493.300 - Notice of default and claims for loss.

Code of Federal Regulations, 2012 CFR

2012-01-01

... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility... notice of default to CCC as soon as possible, but not later than ten days after the date that payment was... Treasurer, CCC, at the address specified in the Contacts P/R. If the exporter or the exporter's assignee...

7 CFR 1403.8 - Withholding.

Code of Federal Regulations, 2011 CFR

2011-01-01

... payable to a debtor by CCC to ensure that the interests of CCC and the United States will be protected as provided in this section. (b) A payment may be withheld to protect the interests of CCC or the United States only if CCC determines that: (1) There has been a serious breach of contract or violation of...

7 CFR 17.9 - CCC payment to suppliers.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 1 2014-01-01 2014-01-01 false CCC payment to suppliers. 17.9 Section 17.9... TITLE I OF THE AGRICULTURAL TRADE DEVELOPMENT AND ASSISTANCE ACT OF 1954, AS AMENDED § 17.9 CCC payment to suppliers. (a) General. (1) The supplier shall request payment from CCC for the amount of the...

7 CFR 1405.1 - Interest.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) Except as may otherwise be determined by CCC as provided in individual program regulations, program contracts or such other means as deemed appropriate by CCC the rate of interest that is applicable to CCC loans shall be equal to the rate of interest charged by the U.S. Treasury for funds borrowed by CCC on...

7 CFR 1488.12 - Coverage of bank obligations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Bank... when determined by the President or Vice President, CCC after consultation with the Controller, CCC, to be in the interest of CCC. (c) A U.S. bank must confirm the full amount of an obligation issued by...

7 CFR 1494.501 - Submission of offers to CCC.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Submission of offers to CCC. 1494.501 Section 1494....501 Submission of offers to CCC. (a) Consideration of offers. Unless otherwise specified in the Invitation, CCC will consider offers on a daily basis from the date of issuance of the Invitation until such...

7 CFR 1427.21 - Settlement.

Code of Federal Regulations, 2012 CFR

2012-01-01

... § 1427.21 Settlement. (a) The settlement of cotton loans will be made by CCC on the basis of the quality and quantity of the cotton delivered to CCC by the producer or acquired by CCC subject to the producer... maximum storage credit rates as determined and announced by CCC. (b) For purposes of settlements for...

7 CFR 1494.501 - Submission of offers to CCC.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Submission of offers to CCC. 1494.501 Section 1494... Program Operations § 1494.501 Submission of offers to CCC. (a) Consideration of offers. Unless otherwise specified in the Invitation, CCC will consider offers on a daily basis from the date of issuance of the...

7 CFR 1962.19 - Claims against Commodity Credit Corporation (CCC).

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 14 2010-01-01 2009-01-01 true Claims against Commodity Credit Corporation (CCC... Liquidation of Chattel Security § 1962.19 Claims against Commodity Credit Corporation (CCC). This section is based on a Memorandum of Understanding between CCC and FmHA or its successor agency under Public Law 103...

7 CFR 1405.1 - Interest.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) Except as may otherwise be determined by CCC as provided in individual program regulations, program contracts or such other means as deemed appropriate by CCC the rate of interest that is applicable to CCC loans shall be equal to the rate of interest charged by the U.S. Treasury for funds borrowed by CCC on...

7 CFR 1405.1 - Interest.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) Except as may otherwise be determined by CCC as provided in individual program regulations, program contracts or such other means as deemed appropriate by CCC the rate of interest that is applicable to CCC loans shall be equal to the rate of interest charged by the U.S. Treasury for funds borrowed by CCC on...

7 CFR 1488.12 - Coverage of bank obligations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Bank... when determined by the President or Vice President, CCC after consultation with the Controller, CCC, to be in the interest of CCC. (c) A U.S. bank must confirm the full amount of an obligation issued by...

7 CFR 1962.19 - Claims against Commodity Credit Corporation (CCC).

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 14 2011-01-01 2011-01-01 false Claims against Commodity Credit Corporation (CCC... Liquidation of Chattel Security § 1962.19 Claims against Commodity Credit Corporation (CCC). This section is based on a Memorandum of Understanding between CCC and FmHA or its successor agency under Public Law 103...

7 CFR 1427.21 - Settlement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... § 1427.21 Settlement. (a) The settlement of cotton loans will be made by CCC on the basis of the quality and quantity of the cotton delivered to CCC by the producer or acquired by CCC subject to the producer... maximum storage credit rates as determined and announced by CCC. (b) For purposes of settlements for...

7 CFR 17.9 - CCC payment to suppliers.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 1 2010-01-01 2010-01-01 false CCC payment to suppliers. 17.9 Section 17.9... TITLE I OF THE AGRICULTURAL TRADE DEVELOPMENT AND ASSISTANCE ACT OF 1954, AS AMENDED § 17.9 CCC payment to suppliers. (a) General. (1) The supplier shall request payment from CCC for the amount of the...

Compulsory commitment to care of substance misusers: international trends during 25 Years.

PubMed

Israelsson, Magnus; Gerdner, Arne

2012-01-01

The study explores international trends in law on compulsory commitment to care of substance misusers (CCC), and two subtypes - civil CCC and CCC within criminal justice legislation - as well as maximum length and amount of applications of such care. The time period covers more than 25 years, and a total of 104 countries and territories. The study is based on available data in three times of observation (1986, 1999 and 2009). Applications of CCC in number of cases are studied on European level for the years 2002-2006. Trends are analyzed using nonparametric tests and general linear models for repeated measures. Findings are discussed from contextual analysis. There is a trend towards decrease in the number of countries worldwide having civil CCC legislation after the millennium, while CCC under criminal law has increased since the mid-1980s, resulting in some total net decrease. The shift results in longer mean duration of CCC and an increase in the number of cases sentenced. There is a risk that the shift from civil CCC to penal CCC implies more focus on young out-acting males in compulsory treatment and that the societal responsibility for more vulnerable persons might be neglected. Copyright © 2012 S. Karger AG, Basel.

Welfare, temperance and compulsory commitment to care for persons with substance misuse problems: a comparative study of 38 European countries.

PubMed

Israelsson, Magnus

2011-01-01

The study explores the existence and types of law on compulsory commitment to care (CCC) of adult substance misusers in Europe and how such laws are related to variations in demographics, alcohol consumption and epidemiology in misuse of opiates, cocaine, amphetamines, temperance culture heritage, health and welfare expenditure, and involvement and role of the state in welfare distribution. Legal information on laws on CCC of misusers was obtained primarily through a survey of 38 European countries. Predictors of laws on CCC, and types of such, were analyzed from country descriptors in multivariate models. A majority (74%) of the explored countries have a law concerning CCC. The most common type of CCC law is within criminal justice legislation (45%), but civil CCC is almost as frequent (37%). These two models of CCC legislation are related to differences in cultural heritage and welfare distribution models. Temperance cultures, i.e. countries with a history of a strong temperance movement, and countries with a Beveridgean distribution of welfare, i.e. through the state, tend to favor civil CCC, while countries with a Bismarckian distribution of welfare, i.e. through insurance with less state interference, tend to favor CCC within criminal justice legislation. Copyright © 2011 S. Karger AG, Basel.

The relationship between ischaemia-modified albumin and good coronary collateral circulation.

PubMed

Gök, Murat; Kundi, Harun; Kızıltunç, Emrullah; Topcuoglu, Canan; Ornek, Ender

2018-01-01

It is important to determine the grade of the coronary collateral circulation (CCC) in patients with stable coronary artery disease. In this study, we aimed to investigate the relationship between the ischaemia-modified albumin (IMA) level and good CCC. A total of 95 patients with coronary angiography and at least one epicardial coronary artery obstruction were included in the study. The Rentrop classification was used with CCC grading, where 0 and 1 were defined as poor collateral, and 2 and 3 were defined as good collateral. The IMA level of the patients was measured using an enzyme-linked immunosorbent assay (ELISA). The receiver-operating characteristic curve was used to show the sensitivity and specificity of IMA levels and the optimal cut-off value for predicting good CCC. The multiple logistic regression analysis revealed that the IMA level in the good CCC group was higher (p < 0.045). Conversely, the high-sensitivity C-reactive protein level was lower in the good CCC group (p < 0.023). We found an IMA cut-off value (4.7 ng/mL) that indicated good CCC level, and this shows good CCC with 70.2% sensitivity and 60.3% specificity. The IMA level could serve as a simple and useful predictor of well-developed CCC.

Epigenetic determinants of ovarian clear cell carcinoma biology

PubMed Central

Yamaguchi, Ken; Huang, Zhiqing; Matsumura, Noriomi; Mandai, Masaki; Okamoto, Takako; Baba, Tsukasa; Konishi, Ikuo; Berchuck, Andrew; Murphy, Susan K.

2015-01-01

Targeted approaches have revealed frequent epigenetic alterations in ovarian cancer, but the scope and relation of these changes to histologic subtype of disease is unclear. Genome-wide methylation and expression data for 14 clear cell carcinoma (CCC), 32 non-CCC, and 4 corresponding normal cell lines were generated to determine how methylation profiles differ between cells of different histological derivations of ovarian cancer. Consensus clustering showed that CCC is epigenetically distinct. Inverse relationships between expression and methylation in CCC were identified, suggesting functional regulation by methylation, and included 22 hypomethylated (UM) genes and 276 hypermethylated (HM) genes. Categorical and pathway analyses indicated that the CCC-specific UM genes were involved in response to stress and many contain hepatocyte nuclear factor (HNF) 1 binding sites, while the CCC-specific HM genes included members of the estrogen receptor alpha (ERalpha) network and genes involved in tumor development. We independently validated the methylation status of 17 of these pathway-specific genes, and confirmed increased expression of HNF1 network genes and repression of ERalpha pathway genes in CCC cell lines and primary cancer tissues relative to non-CCC specimens. Treatment of three CCC cell lines with the demethylating agent Decitabine significantly induced expression for all five genes analyzed. Coordinate changes in pathway expression were confirmed using two primary ovarian cancer datasets (p<0.0001 for both). Our results suggest that methylation regulates specific pathways and biological functions in CCC, with hypomethylation influencing the characteristic biology of the disease while hypermethylation contributes to the carcinogenic process. PMID:24382740

Grapevine and Arabidopsis Cation-Chloride Cotransporters Localize to the Golgi and Trans-Golgi Network and Indirectly Influence Long-Distance Ion Transport and Plant Salt Tolerance1[OPEN

PubMed Central

Henderson, Sam W.; Wege, Stefanie; Qiu, Jiaen; Blackmore, Deidre H.; Walker, Amanda R.; Tyerman, Stephen D.; Walker, Rob R.; Gilliham, Matthew

2015-01-01

Plant cation-chloride cotransporters (CCCs) have been implicated in conferring salt tolerance. They are predicted to improve shoot salt exclusion by directly catalyzing the retrieval of sodium (Na+) and chloride (Cl−) ions from the root xylem. We investigated whether grapevine (Vitis vinifera [Vvi]) CCC has a role in salt tolerance by cloning and functionally characterizing the gene from the cultivar Cabernet Sauvignon. Amino acid sequence analysis revealed that VviCCC shares a high degree of similarity with other plant CCCs. A VviCCC-yellow fluorescent protein translational fusion protein localized to the Golgi and the trans-Golgi network and not the plasma membrane when expressed transiently in tobacco (Nicotiana benthamiana) leaves and Arabidopsis (Arabidopsis thaliana) mesophyll protoplasts. AtCCC-green fluorescent protein from Arabidopsis also localized to the Golgi and the trans-Golgi network. In Xenopus laevis oocytes, VviCCC targeted to the plasma membrane, where it catalyzed bumetanide-sensitive 36Cl–, 22Na+, and 86Rb+ uptake, suggesting that VviCCC (like AtCCC) belongs to the Na+-K+-2Cl– cotransporter class of CCCs. Expression of VviCCC in an Arabidopsis ccc knockout mutant abolished the mutant’s stunted growth phenotypes and reduced shoot Cl– and Na+ content to wild-type levels after growing plants in 50 mm NaCl. In grapevine roots, VviCCC transcript abundance was not regulated by Cl– treatment and was present at similar levels in both the root stele and cortex of three Vitis spp. genotypes that exhibit differential shoot salt exclusion. Our findings indicate that CCC function is conserved between grapevine and Arabidopsis, but neither protein is likely to directly mediate ion transfer with the xylem or have a direct role in salt tolerance. PMID:26378102

The glucose sensor Snf1 and the transcription factors Msn2 and Msn4 regulate transcription of the vacuolar iron importer gene CCC1 and iron resistance in yeast.

PubMed

Li, Liangtao; Kaplan, Jerry; Ward, Diane M

2017-09-15

The budding yeast Saccharomyces cerevisiae stores iron in the vacuole, which is a major resistance mechanism against iron toxicity. One key protein involved in vacuolar iron storage is the iron importer Ccc1, which facilitates iron entry into the vacuole. Transcription of the CCC1 gene is largely regulated by the binding of iron-sulfur clusters to the activator domain of the transcriptional activator Yap5. Additional evidence, however, suggests that Yap5-independent transcriptional activation of CCC1 also contributes to iron resistance. Here, we demonstrate that components of the signaling pathway involving the low-glucose sensor Snf1 regulate CCC1 transcription and iron resistance. We found that SNF1 deletion acts synergistically with YAP5 deletion to regulate CCC1 transcription and iron resistance. A kinase-dead mutation of Snf1 lowered iron resistance as did deletion of SNF4 , which encodes a partner protein of Snf1. Deletion of all three alternative partners of Snf1 encoded by SIT1 , SIT2 , and GAL83 decreased both CCC1 transcription and iron resistance. The Snf1 complex is known to activate the general stress transcription factors Msn2 and Msn4. We show that Msn2 and Msn4 contribute to Snf1-mediated CCC1 transcription. Of note, SNF1 deletion in combination with MSN2 and MSN4 deletion resulted in additive effects on CCC1 transcription, suggesting that other activators contribute to the regulation of CCC1 transcription. In conclusion, we show that yeast have developed multiple transcriptional mechanisms to regulate Ccc1 expression and to protect against high cytosolic iron toxicity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Relationship of mean platelet volume to lymphocyte ratio and coronary collateral circulation in patients with stable angina pectoris.

PubMed

Ornek, Ender; Kurtul, Alparslan

2017-09-01

In patients with coronary artery disease, coronary collateral circulation (CCC) develops as an adaptation to ischemia and contributes toward reduction of cardiovascular events. Recently, the mean platelet volume-to-lymphocyte ratio (MPVLR) has emerged as a novel and readily available marker of inflammation and thrombosis. This study aimed to investigate the relationship between MPVLR and development of CCC. A total of 332 patients with stable angina pectoris undergoing coronary arteriography were enrolled and divided on the basis of the development of CCC into two groups: group with adequate CCC (n=243) and group with impaired CCC (n=89). Routine complete blood count parameters and high-sensitivity C-reactive protein (hsCRP) were measured before coronary arteriography. Both MPVLR and hsCRP levels were higher in the impaired CCC group (P<0.001 and P=0.007, respectively). Multivariate logistic regression analysis indicated that MPVLR was associated independently with impaired CCC [odds ratio (OR): 1.706, 95% confidence interval (CI): 1.328-2.192, P<0.001]. In addition to MPVLR, hsCRP (OR: 1.144, P=0.030) and fasting blood glucose (OR: 1.007, P=0.049) were also associated independently with impaired CCC. In receiver operating characteristics curve analysis, an optimal cut-off point for MPVLR (4.47) was found to predict the presence of good CCC with a sensitivity of 75.3% and a specificity of 71.2% (P<0001). Our findings suggest that measurement of MPVLR may predict the development of CCC in patients with stable coronary artery disease. An increased MPVLR is associated independently with impaired CCC in these patients.

Coprinus comatus Cap Inhibits Adipocyte Differentiation via Regulation of PPARγ and Akt Signaling Pathway

PubMed Central

Jang, Sun-Hee; Kang, Suk Nam; Jeon, Beong-Sam; Ko, Yeoung-Gyu; Kim, Hong-Duck; Won, Chung-Kil; Kim, Gon-Sup; Cho, Jae-Hyeon

2014-01-01

This study assessed the effects of Coprinus comatus cap (CCC) on adipogenesis in 3T3-L1 adipocytes and the effects of CCC on the development of diet-induced obesity in rats. Here, we showed that the CCC has an inhibitory effect on the adipocyte differentiation of 3T3-L1 cells, resulting in a significant decrease in lipid accumulation through the downregulation of several adipocyte specific-transcription factors, including CCAAT/enhancer binding protein β, C/EBPδ, and peroxisome proliferator-activated receptor gamma (PPARγ). Moreover, treatment with CCC during adipocyte differentiation induced a significant down-regulation of PPARγ and adipogenic target genes, including adipocyte protein 2, lipoprotein lipase, and adiponectin. Interestingly, the CCC treatment of the 3T3-L1 adipocytes suppressed the insulin-stimulated Akt and GSK3β phosphorylation, and these effects were stronger in the presence of an inhibitor of Akt phosphorylation, LY294002, suggesting that CCC inhibited adipocyte differentiation through the down-regulation of Akt signaling. In the animal study, CCC administration significantly reduced the body weight and adipose tissue weight of rats fed a high fat diet (HFD) and attenuated lipid accumulation in the adipose tissues of the HFD-induced obese rats. The size of the adipocyte in the epididymal fat of the CCC fed rats was significantly smaller than in the HFD rats. CCC treatment significantly reduced the total cholesterol and triglyceride levels in the serum of HFD rats. These results strongly indicated that the CCC-mediated decrease in body weight was due to a reduction in adipose tissue mass. The expression level of PPARγ and phospho-Akt was significantly lower in the CCC-treated HFD rats than that in the HFD obesity rats. These results suggested that CCC inhibited adipocyte differentiation by the down-regulation of major transcription factor involved in the adipogenesis pathway including PPARγ through the regulation of the Akt pathway in 3T3-L1 cells and HFD adipose tissue. PMID:25181477

Mössbauer, EPR, and Modeling Study of Iron Trafficking and Regulation in Δccc1 and CCC1-up Saccharomyces cerevisiae

PubMed Central

2015-01-01

Strains lacking and overexpressing the vacuolar iron (Fe) importer CCC1 were characterized using Mössbauer and EPR spectroscopies. Vacuolar Fe import is impeded in Δccc1 cells and enhanced in CCC1-up cells, causing vacuolar Fe in these strains to decline and accumulate, respectively, relative to WT cells. Cytosolic Fe levels should behave oppositely. The Fe content of Δccc1 cells grown under low-Fe conditions was similar to that in WT cells. Most Fe was mitochondrial with some nonheme high spin (NHHS) FeII present. Δccc1 cells grown with increasing Fe concentration in the medium contained less total Fe, less vacuolar HS FeIII, and more NHHS FeII than in comparable WT cells. As the Fe concentration in the growth medium increased, the concentration of HS FeIII in Δccc1 cells increased to just 60% of WT levels, while NHHS FeII increased to twice WT levels, suggesting that the NHHS FeII was cytosolic. Δccc1 cells suffered more oxidative damage than WT cells, suggesting that the accumulated NHHS FeII promoted Fenton chemistry. The Fe concentration in CCC1-up cells was higher than in WT cells; the extra Fe was present as NHHS FeII and FeIII and as FeIII oxyhydroxide nanoparticles. These cells contained less mitochondrial Fe and exhibited less ROS damage than Δccc1 cells. CCC1-up cells were adenine-deficient on minimal medium; supplementing with adenine caused a decline of NHHS FeII suggesting that some of the NHHS FeII that accumulated in these cells was associated with adenine deficiency rather than the overexpression of CCC1. A mathematical model was developed that simulated changes in Fe distributions. Simulations suggested that only a modest proportion of the observed NHHS FeII in both strains was the cytosolic form of Fe that is sensed by the Fe import regulatory system. The remainder is probably generated by the reduction of the vacuolar NHHS FeIII species. PMID:24785783

Mössbauer, EPR, and modeling study of iron trafficking and regulation in Δccc1 and CCC1-up Saccharomyces cerevisiae.

PubMed

Cockrell, Allison; McCormick, Sean P; Moore, Michael J; Chakrabarti, Mrinmoy; Lindahl, Paul A

2014-05-13

Strains lacking and overexpressing the vacuolar iron (Fe) importer CCC1 were characterized using Mössbauer and EPR spectroscopies. Vacuolar Fe import is impeded in Δccc1 cells and enhanced in CCC1-up cells, causing vacuolar Fe in these strains to decline and accumulate, respectively, relative to WT cells. Cytosolic Fe levels should behave oppositely. The Fe content of Δccc1 cells grown under low-Fe conditions was similar to that in WT cells. Most Fe was mitochondrial with some nonheme high spin (NHHS) Fe(II) present. Δccc1 cells grown with increasing Fe concentration in the medium contained less total Fe, less vacuolar HS Fe(III), and more NHHS Fe(II) than in comparable WT cells. As the Fe concentration in the growth medium increased, the concentration of HS Fe(III) in Δccc1 cells increased to just 60% of WT levels, while NHHS Fe(II) increased to twice WT levels, suggesting that the NHHS Fe(II) was cytosolic. Δccc1 cells suffered more oxidative damage than WT cells, suggesting that the accumulated NHHS Fe(II) promoted Fenton chemistry. The Fe concentration in CCC1-up cells was higher than in WT cells; the extra Fe was present as NHHS Fe(II) and Fe(III) and as Fe(III) oxyhydroxide nanoparticles. These cells contained less mitochondrial Fe and exhibited less ROS damage than Δccc1 cells. CCC1-up cells were adenine-deficient on minimal medium; supplementing with adenine caused a decline of NHHS Fe(II) suggesting that some of the NHHS Fe(II) that accumulated in these cells was associated with adenine deficiency rather than the overexpression of CCC1. A mathematical model was developed that simulated changes in Fe distributions. Simulations suggested that only a modest proportion of the observed NHHS Fe(II) in both strains was the cytosolic form of Fe that is sensed by the Fe import regulatory system. The remainder is probably generated by the reduction of the vacuolar NHHS Fe(III) species.

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

Vikraman, S; Ramu, M; Karrthick, Kp

Purpose: The purpose of this study was to validate the advent of COMPASS 3D dosimetry as a routine pre treatment verification tool with commercially available CMS Monaco and Oncentra Masterplan planning system. Methods: Twenty esophagus patients were selected for this study. All these patients underwent radical VMAT treatment in Elekta Linac and plans were generated in Monaco v5.0 with MonteCarlo(MC) dose calculation algorithm. COMPASS 3D dosimetry comprises an advanced dose calculation algorithm of collapsed cone convolution(CCC). To validate CCC algorithm in COMPASS, The DICOM RT Plans generated using Monaco MC algorithm were transferred to Oncentra Masterplan v4.3 TPS. Only finalmore » dose calculations were performed using CCC algorithm with out optimization in Masterplan planning system. It is proven that MC algorithm is an accurate algorithm and obvious that there will be a difference with MC and CCC algorithms. Hence CCC in COMPASS should be validated with other commercially available CCC algorithm. To use the CCC as pretreatment verification tool with reference to MC generated treatment plans, CCC in OMP and CCC in COMPASS were validated using dose volume based indices such as D98, D95 for target volumes and OAR doses. Results: The point doses for open beams were observed <1% with reference to Monaco MC algorithms. Comparisons of CCC(OMP) Vs CCC(COMPASS) showed a mean difference of 1.82%±1.12SD and 1.65%±0.67SD for D98 and D95 respectively for Target coverage. Maximum point dose of −2.15%±0.60SD difference was observed in target volume. The mean lung dose of −2.68%±1.67SD was noticed between OMP and COMPASS. The maximum point doses for spinal cord were −1.82%±0.287SD. Conclusion: In this study, the accuracy of CCC algorithm in COMPASS 3D dosimetry was validated by compared with CCC algorithm in OMP TPS. Dose calculation in COMPASS is feasible within < 2% in comparison with commercially available TPS algorithms.« less

[The relationship between fragmented QRS complex and coronary collateral circulation in patients with chronic total occlusion lesion without prior myocardial infarction].

PubMed

Gu, X J; Shan, S J; Liu, Z Z; Jin, G Z; Hu, Z Y; Zhu, L L; Zhang, J

2017-04-24

Objective: To explore the relationship between fragmented QRS complex(fQRS) and coronary collateral circulation(CCC) in patients with chronic total occlusion(CTO)lesion without prior myocardial infarction. Methods: This retrospective study analyzed 238 consecutive patients with CTO lesion in one of the major coronary arteries from May 2014 to October 2015 in our department. Patients were divided into poor CCC group (grade 0 and 1, 58 cases) and good CCC group(grade 2 and 3, 180 cases) based on Rentrop's classification of CCC. The fQRS was defined as the presence of an additional R wave or notching of R or S wave or the presence of fragmentation in two contiguous electrocardiogram leads corresponding to a major coronary artery territory. Multivariate logistic regression was used to analyze the relationship between CCC and fQRS on electrocardiogram. Results: Compared with good CCC group, patients in poor CCC group had older age((65.2±8.9)years old vs. (60.3±10.1) years old, P =0.03), higher plasma glucose ((7.22±3.00) mmol/L vs.(6.31±1.83)mmol/L, P =0.04), and lower left ventricular ejection fraction ((45.2±11.4)% vs. (51.2±13.5)%, P =0.02). None of patients had Rentrop grade 0, the presence of fQRS on ECG in patients with Rentrop grade 1, grade 2, and grade 3 CCC was 69.0% (40/58), 48.6% (35/72) , and 19.4% (21/108), respectively ( P <0.01). The presence of fQRS were higher in poor CCC group than in good CCC group (69.0%(40/58)vs. 31.1%(56/180), P <0.01), and number of leads with fQRS were higher in poor CCC group than in good CCC group (3(0, 4)vs.0(0, 3), P <0.01). Multivariate logistic regression analysis demonstrated that poor CCC growth in patients with CTO lesion without prior myocardial infarction was independently related to the presence of fQRS ( OR =3.659, 95% CI 1.619-8.217, P <0.01). Conclusion: Poor CCC in patients with CTO lesion without prior myocardial infarction is independently related to the presence of fQRS on electrocardiogram.

7 CFR 1425.7 - Suspension and termination of approval.

Code of Federal Regulations, 2014 CFR

2014-01-01

... ASSOCIATIONS § 1425.7 Suspension and termination of approval. (a) CCC may suspend a CMA from obtaining loans and LDP's when CCC determines the CMA has not: (1) Operated according to the CMA's application for... deficiencies of the CMA's operation as noted by CCC; or (4) Violated any of its agreements with CCC. (b) A...

7 CFR 1468.33 - Performance based upon advice or action of representatives of CCC.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Performance based upon advice or action of representatives of CCC. 1468.33 Section 1468.33 Agriculture Regulations of the Department of Agriculture... representatives of CCC. If a participant relied upon the advice or action of any authorized representative of CCC...

7 CFR 1425.7 - Suspension and termination of approval.

Code of Federal Regulations, 2013 CFR

2013-01-01

... ASSOCIATIONS § 1425.7 Suspension and termination of approval. (a) CCC may suspend a CMA from obtaining loans and LDP's when CCC determines the CMA has not: (1) Operated according to the CMA's application for... deficiencies of the CMA's operation as noted by CCC; or (4) Violated any of its agreements with CCC. (b) A...

7 CFR 1486.403 - What expenditures may CCC reimburse under the program?

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false What expenditures may CCC reimburse under the program... Contributions and Reimbursements § 1486.403 What expenditures may CCC reimburse under the program? (a) A... section, CCC will reimburse, in whole or in part, the cost of: (1) Salaries and benefits of the Recipient...

7 CFR 1468.33 - Performance based upon advice or action of representatives of CCC.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false Performance based upon advice or action of representatives of CCC. 1468.33 Section 1468.33 Agriculture Regulations of the Department of Agriculture... representatives of CCC. If a participant relied upon the advice or action of any authorized representative of CCC...

7 CFR 1468.33 - Performance based upon advice or action of representatives of CCC.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Performance based upon advice or action of representatives of CCC. 1468.33 Section 1468.33 Agriculture Regulations of the Department of Agriculture... representatives of CCC. If a participant relied upon the advice or action of any authorized representative of CCC...

7 CFR 1486.403 - What expenditures may CCC reimburse under the program?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false What expenditures may CCC reimburse under the program... MARKETS PROGRAM Contributions and Reimbursements § 1486.403 What expenditures may CCC reimburse under the... paragraph (a) of this section, CCC will reimburse, in whole or in part, the cost of: (1) Salaries and...

7 CFR 1425.7 - Suspension and termination of approval.

Code of Federal Regulations, 2012 CFR

2012-01-01

... ASSOCIATIONS § 1425.7 Suspension and termination of approval. (a) CCC may suspend a CMA from obtaining loans and LDP's when CCC determines the CMA has not: (1) Operated according to the CMA's application for... deficiencies of the CMA's operation as noted by CCC; or (4) Violated any of its agreements with CCC. (b) A...

7 CFR 1468.33 - Performance based upon advice or action of representatives of CCC.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false Performance based upon advice or action of representatives of CCC. 1468.33 Section 1468.33 Agriculture Regulations of the Department of Agriculture... representatives of CCC. If a participant relied upon the advice or action of any authorized representative of CCC...

7 CFR 1425.7 - Suspension and termination of approval.

Code of Federal Regulations, 2011 CFR

2011-01-01

... ASSOCIATIONS § 1425.7 Suspension and termination of approval. (a) CCC may suspend a CMA from obtaining loans and LDP's when CCC determines the CMA has not: (1) Operated according to the CMA's application for... deficiencies of the CMA's operation as noted by CCC; or (4) Violated any of its agreements with CCC. (b) A...

7 CFR 1468.33 - Performance based upon advice or action of representatives of CCC.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false Performance based upon advice or action of representatives of CCC. 1468.33 Section 1468.33 Agriculture Regulations of the Department of Agriculture... representatives of CCC. If a participant relied upon the advice or action of any authorized representative of CCC...

7 CFR 1425.7 - Suspension and termination of approval.

Code of Federal Regulations, 2010 CFR

2010-01-01

... ASSOCIATIONS § 1425.7 Suspension and termination of approval. (a) CCC may suspend a CMA from obtaining loans and LDP's when CCC determines the CMA has not: (1) Operated according to the CMA's application for... deficiencies of the CMA's operation as noted by CCC; or (4) Violated any of its agreements with CCC. (b) A...

7 CFR 1486.403 - What expenditures may CCC reimburse under the program?

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false What expenditures may CCC reimburse under the program... Contributions and Reimbursements § 1486.403 What expenditures may CCC reimburse under the program? (a) A... section, CCC will reimburse, in whole or in part, the cost of: (1) Salaries and benefits of the Recipient...

Closed-Form Evaluation of Mutual Coupling in a Planar Array of Circular Apertures

NASA Technical Reports Server (NTRS)

Bailey, M. C.

1996-01-01

The integral expression for the mutual admittance between circular apertures in a planar array is evaluated in closed form. Very good accuracy is realized when compared with values that were obtained by numerical integration. Utilization of this closed-form expression, for all element pairs that are separated by more than one element spacing, yields extremely accurate results and significantly reduces the computation time that is required to analyze the performance of a large electronically scanning antenna array.

Update Treatment for HBV Infection and Persistent Risk for Hepatocellular Carcinoma: Prospect for an HBV Cure.

PubMed

Yoo, Joseph; Hann, Hie-Won; Coben, Robert; Conn, Mitchell; DiMarino, Anthony J

2018-04-20

Since the discovery of the hepatitis B virus (HBV) by Blumberg et al. in 1965, its genome, sequence, epidemiology, and hepatocarcinogenesis have been elucidated. Globally, hepatitis B virus (HBV) is still responsible for the majority of hepatocellular carcinoma (HCC). HCC is the sixth-most common cancer in the world and the second-most common cancer death. The ultimate goal of treating HBV infection is the prevention of HCC. Fortunately, anti-HBV treatment with nucleos(t)ide analogues (NAs), which began with lamivudine in 1998, has resulted in remarkable improvements in the survival of patients with chronic hepatitis B and a reduced incidence of HCC. These results were documented with lamivudine, entecavir, and tenofovir. Nonetheless, as the duration of antiviral treatment increases, the risk for HCC still remains despite undetectable HBV DNA in serum, as reported by different investigators with observation up to 4⁻5 years. In our own experience, we are witnessing the development of HCC in patients who have received antiviral treatment. Some have enjoyed negative serum HBV DNA for over 12 years before developing HCC. Current treatment with NAs can effectively suppress the replication of the virus but cannot eradicate the covalently closed circular DNA (cccDNA) that is within the nucleus of hepatocytes. There still remains a great need for a cure for HBV. Fortunately, several compounds have been identified that have the potential to eradicate HBV, and there are ongoing clinical trials in progress in their early stages.

7 CFR 1493.490 - Proof of entry.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program... translation acceptable to CCC. Records acceptable to meet this requirement include an original certification...

7 CFR 1493.490 - Proof of entry.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program... translation acceptable to CCC. Records acceptable to meet this requirement include an original certification...

7 CFR 1493.490 - Proof of entry.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program... translation acceptable to CCC. Records acceptable to meet this requirement include an original certification...

Minority Use of a National Cancer Institute-Designated Comprehensive Cancer Center and Non-specialty Hospitals in Two Florida Regions.

PubMed

Sultan, Dawood H; Gishe, Jemal; Hanciles, Angella; Comins, Meg M; Norris, Claire M

2015-09-01

To examine cancer treatment disparities at a National Cancer Institute-designated comprehensive cancer center (NCI-CCC) and non-specialty hospitals. Florida hospital discharge datasets were used. ICD9-CM codes were used to define patients with female reproductive organ cancers (FROC), male reproductive organ cancers (MROC), and OTHER cancer diagnoses. A total of 7462 NCI-CCC patients and 21,875 non-specialty hospital patients were included in the statistical analysis. Data analysis was conducted in SAS 9.2. Increases in age reduced the odds of receiving treatment at the NCI-CCC. Male patients were more likely than female patients to be treated at the NCI-CCC. Age-adjusted odds of African American and Hispanic out/inpatients being treated at the NCI-CCC were significantly lower than those of White out/inpatients. Only patients with workers' compensation, charity, or other insurance had higher odds of being treated at the NCI-CCC. The odds of minority patients receiving outpatient treatment at the NCI-CCC declined after 2005. The odds of receiving inpatient treatment at the NCI-CCC significantly increased after 2006. More targeted outreach by the NCI-CCC is required. However, we expect the creation of local Accountable Care Organizations (ACOs) to reduce the numbers of minority and older patients at the NCI-CCC. Coordinated quality care at ACOs implies a potential for retaining the patient market share held by non-specialty hospitals and a potential for increased demand for ACO care by minority and older patients.

Plasma Omentin-1 Level as a Predictor of Good Coronary Collateral Circulation.

PubMed

Zhou, Ji-Peng; Tong, Xiao-Yu; Zhu, Ling-Ping; Luo, Jing-Min; Luo, Ying; Bai, Yong-Ping; Li, Chuan-Chang; Zhang, Guo-Gang

2017-09-01

Coronary collateral circulation (CCC) is crucial during an acute ischemic attack. Evidences showed that omentin-1 exhibited remarkable antiatherogenic effects and ischemia-induced revascularization. The aim of this study was to investigate the relationship between plasma omentin-1 levels and CCC in patients with ≥90% angiography-proven coronary occlusion. 142 patients with ≥90% luminal diameter stenosis in at least one major epicardial coronary artery were recruited. Among them, 79 patients with Rentrop 0-1 grade were classified into the poor CCC group and 63 patients with Rentrop 2-3 grade were included into the good CCC group. The association between plasma omentin-1 levels and CCC status was assessed. Plasma omentin-1 level was significantly higher in patients with good CCC than those with poor CCC (566.57±26.90 vs. 492.38±19.70 ng/mL, p=0.024). Besides, omentin-1 was positively correlated with total cholesterol (TC), high-density lipoprotein, and gensini score but inversely with hyperlipidemia and body mass index (all p values＜0.05). Multivariate regression analysis indicated that omentin-1 [odds ratio (OR)=1.002, 95% confidence interval (CI): 1.000-1.004, p=0.041)], TC, the number of the diseased vessels, a higher frequency of left circumflex artery and right coronary artery, chronic total occlusion, and gensini score remained as the independent predictors of good CCC. Higher plasma omentin-1 level was associated with better CCC development. Our findings suggest that omentin-1 may be an alternative marker for adequate CCC in patients with ≥90% coronary occlusion.

7 CFR 1493.490 - Proof of entry.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit... translation acceptable to CCC. Records acceptable to meet this requirement include an original certification...

7 CFR 1493.490 - Proof of entry.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit... translation acceptable to CCC. Records acceptable to meet this requirement include an original certification...

7 CFR 1404.6 - Payment to the assignee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... assignee. (a) The assignee shall be paid the smaller of the amount specified on Form CCC-36 or CCC-251 or... indebtedness owed by the assignor to CCC, FSA, or any other agency of the United States shall be subject to offset. (b) Any indebtedness owed by the assignor to CCC or FSA shall be offset from any payment which is...

7 CFR 1404.6 - Payment to the assignee.

Code of Federal Regulations, 2013 CFR

2013-01-01

... assignee. (a) The assignee shall be paid the smaller of the amount specified on Form CCC-36 or CCC-251 or... indebtedness owed by the assignor to CCC, FSA, or any other agency of the United States shall be subject to offset. (b) Any indebtedness owed by the assignor to CCC or FSA shall be offset from any payment which is...

7 CFR 1404.6 - Payment to the assignee.

Code of Federal Regulations, 2012 CFR

2012-01-01

... assignee. (a) The assignee shall be paid the smaller of the amount specified on Form CCC-36 or CCC-251 or... indebtedness owed by the assignor to CCC, FSA, or any other agency of the United States shall be subject to offset. (b) Any indebtedness owed by the assignor to CCC or FSA shall be offset from any payment which is...

7 CFR 1404.6 - Payment to the assignee.

Code of Federal Regulations, 2011 CFR

2011-01-01

... assignee. (a) The assignee shall be paid the smaller of the amount specified on Form CCC-36 or CCC-251 or... indebtedness owed by the assignor to CCC, FSA, or any other agency of the United States shall be subject to offset. (b) Any indebtedness owed by the assignor to CCC or FSA shall be offset from any payment which is...

7 CFR 1404.6 - Payment to the assignee.

Code of Federal Regulations, 2014 CFR

2014-01-01

... assignee. (a) The assignee shall be paid the smaller of the amount specified on Form CCC-36 or CCC-251 or... indebtedness owed by the assignor to CCC, FSA, or any other agency of the United States shall be subject to offset. (b) Any indebtedness owed by the assignor to CCC or FSA shall be offset from any payment which is...

Assessment of training needs and preferences for geographic information systems (GIS) mapping in state comprehensive cancer-control programs.

PubMed

Hopfer, Suellen; Chadwick, Amy E; Parrott, Roxanne L; Ghetian, Christie B; Lengerich, Eugene J

2009-10-01

Geographic information systems (GIS) mapping technologies have potential to advance public health promotion by mapping regional differences in attributes (e.g., disease burden, environmental exposures, access to health care services) to suggest priorities for public health interventions. Training in GIS for comprehensive cancer control (CCC) has been overlooked. State CCC programs' GIS training needs were assessed by interviewing 49 state CCC directors. A majority perceived a need for GIS training, slightly more than half of state CCC programs had access to geocoded data, and the majority of programs did not require continuing education credits of their staff. CCC directors perceived judging maps and realizing their limitations as important skills and identified epidemiologists, CCC staff, public health officials, policy makers, and cancer coalition members as training audiences. They preferred in-class training sessions that last a few hours to a day. Lessons learned are shared to develop training programs with translatable GIS skills for CCC.

The formation of RCCCO and CCC(O)R (R = Me, Ph) neutral radicals from ionic precursors in the gas phase: the rearrangement of CCC(O)Ph.

PubMed

Peppe, Salvatore; McAnoy, Andrew M; Dua, Suresh; Bowie, John H

2004-01-01

Neutrals MeCCCO, CCC(O)Me, PhCCCO and CCC(O)Ph have been made by neutralisation of [MeCCCO](+), [CCC(O)Me](-), [PhCCCO](+) and [CC(CO)Ph](-). Neutrals MeCCCO, CCC(O)Me and PhCCCO are stable for the microsecond duration of the neutralisation experiment. A joint experimental and theoretical study (energies calculated at the B3LYP/aug-cc-pVDZ//B3LYP/6-31G(d) level of theory) suggests that the neutral radical CCC(O)Ph rearranges via a four-centred ipso radical cyclisation/ring opening to form the isomer PhCCCO in an exothermic reaction. (13)C labelling confirms that the rearrangement does not involve O migration. Some of the PhCCCO radicals formed in this reaction are sufficiently energised to effect decomposition to give PhCC and CO. Copyright 2004 John Wiley & Sons, Ltd.

Aiming for cure in HBV and HDV infection.

PubMed

Petersen, Jörg; Thompson, Alexander J; Levrero, Massimo

2016-10-01

Chronic hepatitis B virus (HBV) infection continues to be a major health burden worldwide. Currently available antiviral treatment options for chronic hepatitis B include pegylated interferon alpha2a (PegIFN) or nucleos(t)ide analogues (NAs). The major advantages of NAs are good tolerance and potent antiviral activity associated with high rates of sustained on-treatment response to therapy. The advantages of PegIFN include a finite course of treatment, the absence of drug resistance, and an opportunity to obtain a durable post-treatment response to therapy. Furthermore, PegIFN is the only approved agent known to be active against hepatitis D virus (HDV). The use of these two antiviral agents with different mechanisms of action in combination against hepatitis B is theoretically an attractive approach for treatment. Although several studies have confirmed certain virological advantages of combination therapies, data supporting a long-term clinical benefit for patients are lacking and monotherapy with PegIFN or NAs remains the therapy of choice. Moreover, with the current treatment approaches, only a limited number of patients achieve hepatitis B surface antigen (HBsAg) loss. HBsAg loss is considered a "functional cure", but does not mean viral eradication. There is a need for novel therapeutic approaches that enable not only suppression of viral replication, but resolution of HBV infection. A key challenge is to target covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. The recent development and availability of innovative in vitro and in vivo systems and sensitive molecular techniques has opened new possibilities to study the complex network of interactions that HBV establishes with the host in the course of infection and to define new targets for antiviral strategies. Several new antiviral or immunomodulatory compounds have reached preclinical or clinical testing with the aim of silencing or eradicating cccDNA to achieve functional cure. Many of these strategies may also be effective for the treatment of HDV, which is dependent on HBsAg for its life cycle. This Clinical Trial Watch summarizes the most recent therapeutic strategies designed to directly target the viruses B and D or to improve immune responses during chronic HBV infection. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Influence of Ogg1 repair on the genetic stability of ccc2 mutant of Saccharomyces cerevisiae chemically challenged with 4-nitroquinoline-1-oxide (4-NQO).

PubMed

da Silva, Claudia R; Almeida, Gabriella S; Caldeira-de-Araújo, Adriano; Leitão, Alvaro C; de Pádula, Marcelo

2016-01-01

In Saccharomyces cerevisiae, disruption of genes by deletion allowed elucidation of the molecular mechanisms of a series of human diseases, such as in Wilson disease (WD). WD is a disorder of copper metabolism, due to inherited mutations in human copper-transporting ATPase (ATP7B). An orthologous gene is present in S. cerevisiae, CCC2 gene. Copper is required as a cofactor for a number of enzymes. In excess, however, it is toxic, potentially carcinogenic, leading to many pathological conditions via oxidatively generated DNA damage. Deficiency in ATP7B (human) or Ccc2 (yeast) causes accumulation of intracellular copper, favouring the generation of reactive oxygen species. Thus, it becomes important to study the relative importance of proteins involved in the repair of these lesions, such as Ogg1. Herein, we addressed the influence Ogg1 repair in a ccc2 deficient strain of S. cerevisiae. We constructed ccc2-disrupted strains from S. cerevisiae (ogg1ccc2 and ccc2), which were analysed in terms of viability and spontaneous mutator phenotype. We also investigated the impact of 4-nitroquinoline-1-oxide (4-NQO) on nuclear DNA damage and on the stability of mitochondrial DNA. The results indicated a synergistic effect on spontaneous mutagenesis upon OGG1 and CCC2 double inactivation, placing 8-oxoguanine as a strong lesion-candidate at the origin of spontaneous mutations. The ccc2 mutant was more sensitive to cell killing and to mutagenesis upon 4-NQO challenge than the other studied strains. However, Ogg1 repair of exogenous-induced DNA damage revealed to be toxic and mutagenic to ccc2 deficient cells, which can be due to a detrimental action of Ogg1 on DNA lesions induced in ccc2 cells. Altogether, our results point to a critical and ambivalent role of BER mediated by Ogg1 in the maintenance of genomic stability in eukaryotes deficient in CCC2 gene. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Adolescents and Young Adults with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia: Impact of Care at Specialized Cancer Centers on Survival Outcome

PubMed Central

Wolfson, Julie; Sun, Can-Lan; Wyatt, Laura; Stock, Wendy; Bhatia, Smita

2017-01-01

Background Adolescents and young adults (AYA: 15-39y) with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) experience inferior survival when compared to children. Impact of care at NCI-designated Comprehensive Cancer Centers (CCC; or Children's Oncology Group sites [COG]) on survival disparities remains unstudied. Methods Using the Los Angeles Cancer registry, we identified 1,870 ALL or AML patients between 1 and 39y at diagnosis. Cox regression analyses assessed risk of mortality; younger age+CCC/COG served as the referent group. Logistic regression was used to determine odds of care at CCC/COG, adjusting for variables above. Results ALL outcome: AYAs at non-CCC/COG experienced inferior survival (15-21y: HR=1.9, p=0.005; 22-29y: HR=2.6, p<0.001; 30-39y: HR=3.0, p<0.001). Outcome at CCC/COG was comparable between children and young AYAs (15-21y: HR=1.3, p=0.3; 22-29y: HR=1.2, p=0.2) but was inferior for 30-39yo (HR=3.4, p<0.001). AML outcome: AYAs at non-CCC/COG experienced inferior outcome (15-21y: HR=1.8, p=0.02; 22-39y: HR=1.4, p=0.06). Outcome at CCC/COG was comparable between children and 15-21yo (HR=1.3, p=0.4) but was inferior for 22-39yo (HR=1.7, p=0.05). Access: 15-21yo were less likely to use CCC/COG than children (p<0.001). In 22-39yo, public/uninsured (ALL: p=0.004; AML<0.001), African-American/Hispanics (ALL: p=0.03), and 30-39yo (ALL: p=0.03) were less likely to use CCC/COG. Conclusions Poor survival in AYAs with ALL and AML is mitigated by care at CCC/COG. Barriers to CCC/COG care include public/uninsured, and African-American/Hispanic race/ethnicity. Impact Care at CCC/COG explains, in part, inferior outcomes in AYAs with ALL and AML. Key sociodemographic factors serve as barriers to care at specialized centers. PMID:28209594

Quantifying the condition of eruption column collapse during explosive volcanic eruptions

NASA Astrophysics Data System (ADS)

Koyaguchi, Takehiro; Suzuki, Yujiro

2016-04-01

During an explosive eruption, a mixture of pyroclasts and volcanic gas forms a buoyant eruption column or a pyroclastic flow. Generation of a pyroclastic flow caused by eruption column collapse is one of the most hazardous phenomena during explosive volcanic eruptions. The quantification of column collapse condition (CCC) is, therefore, highly desired for volcanic hazard assessment. Previously the CCC was roughly predicted by a simple relationship between magma discharge rate and water content (e.g., Carazzo et al., 2008). When a crater is present above the conduit, because of decompression/compression process inside/above the crater, the CCC based on this relationship can be strongly modified (Woods and Bower, 1995; Koyaguchi et al., 2010); however, the effects of the crater on CCC has not been fully understood in a quantitative fashion. Here, we have derived a semi-analytical expression of CCC, in which the effects of the crater is taken into account. The CCC depends on magma properties, crater shape (radius, depth and opening angle) as well as the flow rate at the base of crater. Our semi-analytical CCC expresses all these dependencies by a single surface in a parameter space of the dimensionless magma discharge rate, the dimensionless magma flow rate (per unit area) and the ratio of the cross-sectional areas at the top and the base of crater. We have performed a systematic parameter study of three-dimensional (3D) numerical simulations of eruption column dynamics to confirm the semi-analytical CCC. The results of the 3D simulations are consistent with the semi-analytical CCC, while they show some additional fluid dynamical features in the transitional state (e.g., partial column collapse). Because the CCC depends on such many parameters, the scenario towards the generation of pyroclastic flow during explosive eruptions is considered to be diverse. Nevertheless, our semi-analytical CCC together with the existing semi-analytical solution for the 1D conduit flow model (Koyaguchi, 2005) allows us to intuitively and quantitatively understand how the eruption column dynamics approaches to the CCC as the crater radius increases during the waxing stage of an eruption, or as the magma chamber pressure decreases during the waning stage.

Integrated Copy Number and Expression Analysis Identifies Profiles of Whole-Arm Chromosomal Alterations and Subgroups with Favorable Outcome in Ovarian Clear Cell Carcinomas

PubMed Central

Uehara, Yuriko; Oda, Katsutoshi; Ikeda, Yuji; Koso, Takahiro; Tsuji, Shingo; Yamamoto, Shogo; Asada, Kayo; Sone, Kenbun; Kurikawa, Reiko; Makii, Chinami; Hagiwara, Otoe; Tanikawa, Michihiro; Maeda, Daichi; Hasegawa, Kosei; Nakagawa, Shunsuke; Wada-Hiraike, Osamu; Kawana, Kei; Fukayama, Masashi; Fujiwara, Keiichi; Yano, Tetsu; Osuga, Yutaka; Fujii, Tomoyuki; Aburatani, Hiroyuki

2015-01-01

Ovarian clear cell carcinoma (CCC) is generally associated with chemoresistance and poor clinical outcome, even with early diagnosis; whereas high-grade serous carcinomas (SCs) and endometrioid carcinomas (ECs) are commonly chemosensitive at advanced stages. Although an integrated genomic analysis of SC has been performed, conclusive views on copy number and expression profiles for CCC are still limited. In this study, we performed single nucleotide polymorphism analysis with 57 epithelial ovarian cancers (31 CCCs, 14 SCs, and 12 ECs) and microarray expression analysis with 55 cancers (25 CCCs, 16 SCs, and 14 ECs). We then evaluated PIK3CA mutations and ARID1A expression in CCCs. SNP array analysis classified 13% of CCCs into a cluster with high frequency and focal range of copy number alterations (CNAs), significantly lower than for SCs (93%, P < 0.01) and ECs (50%, P = 0.017). The ratio of whole-arm to all CNAs was higher in CCCs (46.9%) than SCs (21.7%; P < 0.0001). SCs with loss of heterozygosity (LOH) of BRCA1 (85%) also had LOH of NF1 and TP53, and LOH of BRCA2 (62%) coexisted with LOH of RB1 and TP53. Microarray analysis classified CCCs into three clusters. One cluster (CCC-2, n = 10) showed more favorable prognosis than the CCC-1 and CCC-3 clusters (P = 0.041). Coexistent alterations of PIK3CA and ARID1A were more common in CCC-1 and CCC-3 (7/11, 64%) than in CCC-2 (0/10, 0%; P < 0.01). Being in cluster CCC-2 was an independent favorable prognostic factor in CCC. In conclusion, CCC was characterized by a high ratio of whole-arm CNAs; whereas CNAs in SC were mainly focal, but preferentially caused LOH of well-known tumor suppressor genes. As such, expression profiles might be useful for sub-classification of CCC, and might provide useful information on prognosis. PMID:26043110

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

Thiyagarajan, Rajesh; Vikraman, S; Karrthick, KP

Purpose: To evaluate the impact of dose calculation algorithm on the dose distribution of biologically optimized Volumatric Modulated Arc Therapy (VMAT) plans for Esophgeal cancer. Methods: Eighteen retrospectively treated patients with carcinoma esophagus were studied. VMAT plans were optimized using biological objectives in Monaco (5.0) TPS for 6MV photon beam (Elekta Infinity). These plans were calculated for final dose using Monte Carlo (MC), Collapsed Cone Convolution (CCC) & Pencil Beam Convolution (PBC) algorithms from Monaco and Oncentra Masterplan TPS. A dose grid of 2mm was used for all algorithms and 1% per plan uncertainty maintained for MC calculation. MC basedmore » calculations were considered as the reference for CCC & PBC. Dose volume histogram (DVH) indices (D95, D98, D50 etc) of Target (PTV) and critical structures were compared to study the impact of all three algorithms. Results: Beam models were consistent with measured data. The mean difference observed in reference with MC calculation for D98, D95, D50 & D2 of PTV were 0.37%, −0.21%, 1.51% & 1.18% respectively for CCC and 3.28%, 2.75%, 3.61% & 3.08% for PBC. Heart D25 mean difference was 4.94% & 11.21% for CCC and PBC respectively. Lung Dmean mean difference was 1.5% (CCC) and 4.1% (PBC). Spinal cord D2 mean difference was 2.35% (CCC) and 3.98% (PBC). Similar differences were observed for liver and kidneys. The overall mean difference found for target and critical structures was 0.71±1.52%, 2.71±3.10% for CCC and 3.18±1.55%, 6.61±5.1% for PBC respectively. Conclusion: We observed a significant overestimate of dose distribution by CCC and PBC as compared to MC. The dose prediction of CCC is closer (<3%) to MC than that of PBC. This can be attributed to poor performance of CCC and PBC in inhomogeneous regions around esophagus. CCC can be considered as an alternate in the absence of MC algorithm.« less

7 CFR 1421.401 - DMA responsibilities.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) Transmit documents to render forfeited collateral to CCC; and (9) Collect data for reporting to CCC as... of the warehouse receipts, unless otherwise directed by CCC. (3) Attend, at the DMAs expense, DMA...

7 CFR 1421.401 - DMA responsibilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) Transmit documents to render forfeited collateral to CCC; and (9) Collect data for reporting to CCC as... of the warehouse receipts, unless otherwise directed by CCC. (3) Attend, at the DMAs expense, DMA...

Association of conjunctival and corneal calcification with vascular calcification among hepatitis-C-seropositive hemodialysis patients.

PubMed

AbouSeif, Khaled; Sany, Dawlat; Elshahawy, Yasser; Seddik, Ayman; Rahman, Khedr; Gaber, Moustapha

2016-01-01

Disorders associated with the hepatitis C virus (HCV) have been reported including cardiovascular, metabolic, and central nervous system diseases. Since chronic HCV infections may be curable, their identification as causal contributors to cardiovascular risk could offer new perspectives in the prevention of cardiovascular disease. The aim of this study is to investigate the association between HCV and aortic arch calcification (AAC) and corneal and conjunctival calcification (CCC) in maintenance hemodialysis (MHD) patients; further, we assessed the correlation of CCC with vascular calcification. A total of 100 patients undergoing hemodialysis (HD) in our hospital were included in this study. Patients underwent a complete ocular examination including intraocular pressure, and CCC was looked for by slit lamp and fundoscopy. CCC was graded according to modified Porter and Crombie classification system described by Tokuyama et al. Helical computerized tomographic chest examination was used to evaluate the grading of AAC. Demographic, hematological, biochemical, and dialysis-related data were obtained. There was significant difference between seropositive (n = 51) and seronegative patients (n = 49) regarding grading of AAC and CCC (P <0.001). Significant positive correlation was found between grading of CCC, AAC, age (P <0.001), duration on HD (P <0.001), HCV-antibody positivity (P <0.001), serum calcium level (P <0.001), serum phosphorus level (P <0.001), calcium × phosphorus product (P <0.001), and i-parathormone level (P < 0.001). In addition, CCC grading positively correlated with AAC. Our results suggest that patients undergoing HD infected with the HCV have high degree of CCC, AAC, and mineral metabolism disorder. The strong correlation between CCC and AAC indicates that CCC evaluation is an easy, fast, non-invasive method, and might be used as an indirect indicator to detect vascular calcification in patients undergoing MHD.

Plasma Omentin-1 Level as a Predictor of Good Coronary Collateral Circulation

PubMed Central

Zhou, Ji-Peng; Tong, Xiao-Yu; Zhu, Ling-Ping; Luo, Jing-Min; Luo, Ying; Bai, Yong-Ping

2017-01-01

Aims: Coronary collateral circulation (CCC) is crucial during an acute ischemic attack. Evidences showed that omentin-1 exhibited remarkable antiatherogenic effects and ischemia-induced revascularization. The aim of this study was to investigate the relationship between plasma omentin-1 levels and CCC in patients with ≥ 90% angiography-proven coronary occlusion. Methods: 142 patients with ≥ 90% luminal diameter stenosis in at least one major epicardial coronary artery were recruited. Among them, 79 patients with Rentrop 0–1 grade were classified into the poor CCC group and 63 patients with Rentrop 2–3 grade were included into the good CCC group. The association between plasma omentin-1 levels and CCC status was assessed. Results: Plasma omentin-1 level was significantly higher in patients with good CCC than those with poor CCC (566.57 ± 26.90 vs. 492.38 ± 19.70 ng/mL, p = 0.024). Besides, omentin-1 was positively correlated with total cholesterol (TC), high-density lipoprotein, and gensini score but inversely with hyperlipidemia and body mass index (all p values < 0.05). Multivariate regression analysis indicated that omentin-1 [odds ratio (OR) = 1.002, 95% confidence interval (CI): 1.000 – 1.004, p = 0.041)], TC, the number of the diseased vessels, a higher frequency of left circumflex artery and right coronary artery, chronic total occlusion, and gensini score remained as the independent predictors of good CCC. Conclusion: Higher plasma omentin-1 level was associated with better CCC development. Our findings suggest that omentin-1 may be an alternative marker for adequate CCC in patients with ≥ 90% coronary occlusion. PMID:28123148

Prognostic value of coronary collaterals in patients with acute coronary syndromes.

PubMed

Kurtul, Alparslan; Ozturk, Selcuk

2017-08-01

The presence of good coronary collateral circulation (CCC) can protect and preserve myocardium from ischemia, increase myocardial contractility, and reduce adverse clinical events. However, its impact on mortality is still a topic of debate, particularly in acute coronary syndrome (ACS). The aim of this study was to investigate the association of CCC with cardiac risk factors and in-hospital mortality in patients hospitalized with a diagnosis of ACS. The study population included 2286 patients with ACS who underwent coronary angiography and were found to have at least 90% significant lesion in at least one major coronary artery. The CCC was graded according to the Rentrop classification. The patients were classified into a poor CCC group (Rentrop grades 0-1, n=1859) or a good CCC group (Rentrop grades 2-3, n=427). Patients with good CCC had more high-risk patient characteristics such as older age, higher rate of Killip class of at least 2 at admission, lower left ventricular ejection fraction, and impaired renal functions compared with the patients with poor CCC. In multivariate analysis, the presence of good CCC [odds ratio (OR): 2.000; 95% confidence interval: 1.116-3.585; P=0.020], left ventricular ejection fraction less than 40% (OR: 2.381; P=0.003), Killip class of at least 2 at admission (OR: 3.609; P<0.001), age of at least 65 years (OR: 2.975; P=0.003), and hemoglobin (OR: 0.797; P=0.003) were independent predictors of in-hospital mortality. In contrast to previous studies, our study did not confirm a beneficial role of good CCC in patients with ACS; the presence of good CCC was even independently associated with increased in-hospital mortality in the multivariate analysis.

Diagnostic value of 3.0T (1)H MRS with choline-containing compounds ratio (∆CCC) in primary malignant hepatic tumors.

PubMed

Zhang, Li; Zhao, Xinming; Ouyang, Han; Wang, Shuang; Zhou, Chunwu

2016-08-22

The purpose of this study was to investigate the diagnostic value of 3.0-T (1)H magnetic resonance spectroscopy ((1)H MRS) in primary malignant hepatic tumors and to compare the effects of (1)H MRS on the diagnostic accuracy of liver-occupying lesions between junior and experienced radiologists. This study included 50 healthy volunteers and 40 consecutive patients (50 lesions). Informed consent was obtained from each subject. Images were obtained on clinical whole-body 3.0-T MR system. Point -Resolved Spectroscopy was used to obtain the spectroscopy image. All conventional images were reviewed blindly by junior radiologist and experienced radiologist, respectively. The choline-containing compounds peak area (CCC-A) was measured with SAGE software, and the choline-containing compound ratio (∆CCC) was calculated. The efficacy of CCC-A and ∆CCC in the diagnosis of primary malignant hepatic tumors was determined by plotting receiver operating characteristic (ROC) curves. We also compared the effects of MRS on the diagnostic accuracy of liver-occupying lesions with junior and experienced radiologist. A significant increase in mean CCC-A was observed in malignant tumors compared with benign tumors. The ROC curve showed ∆CCC had a high discriminatory ability in diagnosing primary malignant hepatic tumors with a sensitivity and specificity of 94.3 and 93.3 %, respectively. The ∆CCC area under the curve (AUC) was 0.97 that was larger than that of both junior and experienced radiologist, while the significantly statistical difference was only obtained between ∆CCC and junior radiologist (P = 0.01). (1)H MRS with ∆CCC demonstrates good efficacy in diagnosing primary malignant hepatic tumors. The technique improves the accuracy of diagnosing liver-occupying lesions, particularly for junior radiologists.

7 CFR 1488.17 - Assignment.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Miscellaneous... under the financing agreement, in whole or in part, without written approval of the Vice President, CCC, or the Controller, CCC. ...

7 CFR 1488.17 - Assignment.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Miscellaneous... under the financing agreement, in whole or in part, without written approval of the Vice President, CCC, or the Controller, CCC. ...

7 CFR 1488.17 - Assignment.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Miscellaneous... under the financing agreement, in whole or in part, without written approval of the Vice President, CCC, or the Controller, CCC. ...

The Effects of Cover, Copy, and Compare, Performance Feedback and Rewards on the Mathematical Calculation Skills of Students Identified with Math Difficulty

ERIC Educational Resources Information Center

Benson, Geetal

2013-01-01

This study examined the isolated effects of Cover, Copy and Compare (CCC) and the effects of CCC paired with performance feedback (CCC + PF) and rewards (CCC + RW) on the mathematical calculation skills of first grade students identified with math difficulty. Four research questions were addressed in this study. 1. Does Cover, Copy, and Compare…

Targeted mutation analysis of endometrial clear cell carcinoma.

PubMed

Hoang, Lien N; McConechy, Melissa K; Meng, Bo; McIntyre, John B; Ewanowich, Carol; Gilks, Cyril Blake; Huntsman, David G; Köbel, Martin; Lee, Cheng-Han

2015-04-01

Endometrial clear cell carcinomas (CCC) constitute fewer than 5% of all carcinomas of the endometrium. Currently, little is known regarding the genetic basis of endometrial CCC. We performed genomic and immunohistochemical analyses on 14 rigorously reviewed pure endometrial CCC. The genomic analysis consisted of sequencing the coding regions of 26 genes implicated previously in endometrial carcinoma. Twelve of 14 tumours displayed a prototypical CCC immunophenotype [napsin A+, hepatocyte nuclear factor-1β (HNF1β(+) ) and oestrogen receptor(-) ] and all showed intact mismatch repair protein expression. We detected mutations in 11 of 14 tumours, and there was a predominance of mutations involving genes that are mutated more frequently in endometrial serous carcinomas than in endometrioid carcinomas. Two tumours displayed a prototypical serous carcinoma mutation profile (concurrent TP53 and PPP2R1A mutations, without PTEN, CTNNB1 or ARID1A mutation). No mutations in PTEN, CTNNB1 or POLE were identified. The overall mutation profile of this cohort of endometrial CCC appears to be more serous-like than endometrioid-like, with a minor subset in the TP53-mutated CCC showing serous carcinoma profile. These findings provide new insights into the molecular features of morphologically prototypical endometrial CCC, and underscore the need for further investigations into the oncogenesis of endometrial CCC. © 2014 John Wiley & Sons Ltd.

Hedgehog pathway as a potential treatment target in human cholangiocarcinoma.

PubMed

Riedlinger, Dorothee; Bahra, Marcus; Boas-Knoop, Sabine; Lippert, Steffen; Bradtmöller, Maren; Guse, Katrin; Seehofer, Daniel; Bova, Roberta; Sauer, Igor M; Neuhaus, Peter; Koch, Arend; Kamphues, Carsten

2014-08-01

Innovative treatment concepts targeting essential signaling pathways may offer new chances for patients suffering from cholangiocarcinoma (CCC). For that, we performed a systematic molecular genetic analysis concerning the Hedgehog activity in human CCC samples and analyzed the effect of Hh inhibition on CCC cells in vitro and in vivo. Activation of the Hh pathway was analyzed in 50 human CCC samples using quantitative polymerase chain reaction (qPCR). The efficacy of Hh inhibition using cyclopamine and BMS-833923 was evaluated in vitro. In addition, the effect of BMS-833923, alone or in combination with gemcitabine, was analyzed in vivo in a murine subcutaneous xenograft model. Expression analysis revealed a significant activation of the Hh-signaling pathway in nearly 50% of CCCs. Hh inhibition resulted in a significant decrease in cell proliferation of CCC cells. Moreover, a distinct inhibition of tumor growth could be seen as a result of a combined therapy with BMS-833923 and gemcitabine in CCC xenografts. The results of our study suggest that the Hh pathway plays a relevant role at least in a subset of human CCC. Inhibition of this pathway may represent a possible treatment option for CCC patients in which the Hh pathway is activated. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Final work plan : investigation of potential contamination at the former CCC/USDA grain storage facility in Hanover, Kansas.

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

LaFreniere, L. M.; Environmental Science Division

The Commodity Credit Corporation (CCC), an agency of the U.S. Department of Agriculture (USDA), operated a grain storage facility at the northeastern edge of the city of Hanover, Kansas, from 1950 until the early 1970s. During this time, commercial grain fumigants containing carbon tetrachloride were in common use by the grain storage industry to preserve grain in their facilities. In February 1998, trace to low levels of carbon tetrachloride (below the maximum contaminant level [MCL] of 5.0 {micro}g/L) were detected in two private wells near the former grain storage facility at Hanover, as part of a statewide USDA private wellmore » sampling program that was implemented by the Kansas Department of Health and Environment (KDHE) near former CCC/USDA facilities. In April 2007, the CCC/USDA collected near-surface soil samples at 1.8-2 ft BGL (below ground level) at 61 locations across the former CCC/USDA facility. All soil samples were analyzed by the rigorous gas chromatograph-mass spectrometer analytical method (purge-and-trap method). No contamination was found in soil samples above the reporting limit of 10 {micro}g/kg. In July 2007, the CCC/USDA sampled indoor air at nine residences on or adjacent to its former facility to address the residents concerns regarding vapor intrusion. Low levels of carbon tetrachloride were detected at four of the nine homes. Because carbon tetrachloride found in private wells and indoor air at the site might be linked to historical use of fumigants containing carbon tetrachloride at its former grain storage facility, the CCC/USDA is proposing to conduct an investigation to determine the source and extent of the carbon tetrachloride contamination associated with the former facility. This investigation will be conducted in accordance with the intergovernmental agreement between the KDHE and the Farm Service Agency (FSA) of the USDA. The investigation at Hanover will be performed, on behalf of the CCC/USDA, by the Environmental Science Division of Argonne National Laboratory. Argonne is a nonprofit, multidisciplinary research center operated by UChicago Argonne, LLC, for the U.S. Department of Energy (DOE). The CCC/USDA has entered into an interagency agreement with DOE, under which Argonne provides technical assistance to the CCC/USDA with environmental site characterization and remediation at its former grain storage facilities. Seven technical objectives have been proposed for the Hanover investigation. They are as follows: (1) Identify the sources and extent of soil contamination beneath the former CCC/USDA facility; (2) Characterize groundwater contamination beneath the former CCC/USDA facility; (3) Determine groundwater flow patterns; (4) Define the vertical and lateral extent of the groundwater plume outside the former CCC/USDA facility; (5) Evaluate the aquifer and monitor the groundwater system; (6) Identify any other potential sources of contamination that are not related to activities of the CCC/USDA; and (7) Determine whether there is a vapor intrusion problem at the site attributable to the former CCC/USDA facility. The technical objectives will be accomplished in a phased approached. Data collected during each phase will be evaluated to determine whether the subsequent phase is necessary. The KDHE project manager and the CCC/USDA will be contacted during each phase and kept apprised of the results. Whether implementation of each phase of work is necessary will be discussed and mutually agreed upon by the CCC/USDA and KDHE project managers.« less

Electron- and positron-impact atomic scattering calculations using propagating exterior complex scaling

NASA Astrophysics Data System (ADS)

Bartlett, P. L.; Stelbovics, A. T.; Rescigno, T. N.; McCurdy, C. W.

2007-11-01

Calculations are reported for four-body electron-helium collisions and positron-hydrogen collisions, in the S-wave model, using the time-independent propagating exterior complex scaling (PECS) method. The PECS S-wave calculations for three-body processes in electron-helium collisions compare favourably with previous convergent close-coupling (CCC) and time-dependent exterior complex scaling (ECS) calculations, and exhibit smooth cross section profiles. The PECS four-body double-excitation cross sections are significantly different from CCC calculations and highlight the need for an accurate representation of the resonant helium final-state wave functions when undertaking these calculations. Results are also presented for positron-hydrogen collisions in an S-wave model using an electron-positron potential of V12 = - (8 + (r1 - r2)2)-1/2. This model is representative of the full problem, and the results demonstrate that ECS-based methods can accurately calculate scattering, ionization and positronium formation cross sections in this three-body rearrangement collision.

7 CFR 1434.19 - Settlement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... FOR HONEY § 1434.19 Settlement. The value of the settlement of loans shall be made by CCC on the... CCC and CCC shall have no obligation to pay such amount to any party. (b) With respect to honey that...

7 CFR 1434.19 - Settlement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... FOR HONEY § 1434.19 Settlement. The value of the settlement of loans shall be made by CCC on the... CCC and CCC shall have no obligation to pay such amount to any party. (b) With respect to honey that...

Synergistic control center development utilizing commercial technology and industry standards. [NASA space programs

NASA Technical Reports Server (NTRS)

Anderson, Brian L.

1993-01-01

The development of the Control Center Complex (CCC), a synergistic control center supporting both the Space Station Freedom and the Space Shuttle Program, is described. To provide maximum growth and flexibility, the CCC uses commercial off-the-shelf technology and industry standards. The discussion covers the development philosophy, CCC architecture, data distribution, the software platform concept, workstation platform, commercial tools for the CCC, and benefits of synergy.

Cortisol levels in fingernails, neurocognitive performance and clinical variables in euthymic bipolar I disorder.

PubMed

Herane-Vives, Andres; Cleare, Anthony J; Chang, Chin-Kuo; de Angel, Valeria; Papadopoulos, Andrew; Fischer, Susanne; Halari, Rozmin; Cheung, Eric Y W; Young, Allan H

2017-03-27

Neurocognitive impairment has been found in bipolar patients. Hypercortisolemia is one possible cause but there has been no agreement on this. Previous sampling methods assessed only acute cortisol levels, whereas the association between cortisol and psychopathology might be better understood by investigating chronic levels. Fingernails are a novel method for measuring chronic cortisol concentration (CCC). Here, we measured CCC in euthymic bipolar disorder I (BD-I) patients and healthy controls using fingernails to investigate whether differences in CCC influenced neurocognitive performance. We also investigated whether differences in clinical illness variables influenced CCC in euthymic BD-I patients. A previous study demonstrated neurocognitive impairment in euthymic BD-I patients. The current study included a portion of this sample: 40 BD-I versus 42 matched controls who provided fingernail samples. There was no statistically significant difference in CCC between controls and BD-I (P = .09). Logistic regression analyses revealed that euthymic bipolar I subjects with more than five years of current euthymia had decreased odds of having higher fingernail cortisol concentration (>71.2 pg/mg) compared to those with less than 1.5 years (P = .04). There was no association between CCC and cognitive impairment in all domains before and after adjustment for age and sex. The current evidence suggests CCC is not a trait biomarker in euthymic BD-I (BD-I). Longer periods of stability in affective disorders are associated with lower CCC. Fingernail cortisol does not seem to be implicated in neurocognitive impairment and BD-I. Future studies may investigate CCC in different illness phases of BD-I.

Angiotensin-converting enzyme DD polymorphism is associated with poor coronary collateral circulation in patients with coronary artery disease.

PubMed

Ceyhan, Koksal; Kadi, Hasan; Celik, Atac; Burucu, Turgay; Koc, Fatih; Sogut, Erkan; Sahin, Semsettin; Onalan, Orhan

2012-01-01

Although association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and cardiovascular diseases was reported by many studies, the relation between ACE I/D polymorphism and coronary collateral circulation (CCC) has not been studied yet. The aim of the present study was to investigate a possible relationship between ACE I/D polymorphism and CCC. Patients who were subjected to coronary angiography in the 2006 to 2009 period and had at least a completely occluded major artery were included in this study. To classify collateral circulation, we used the Rentrop classification. Patients were classified as having poor CCC (Rentrop grades 0 to 1) or good CCC (Rentrop grades 2 to 3). Gene polymorphism was detected through the detailed melting curve analysis of polymerase chain reaction products after amplification using real-time polymerase chain reaction method and LightCycler 1.5 apparatus. We prospectively studied 113 patients who had at least 1 totally occluded major epicardial coronary artery. Forty-seven patients had poor CCC and 67 patients had good CCC. There were no differences among groups in age, sex, risk factors, lipid profile, uses of cardiovascular drugs, and number of diseased vessels. Plasma ACE levels were significantly higher in poor CCC group (P < 0.001). The frequency of DD polymorphism was higher in the poor CCC group (P < 0.001). In allele frequency, we found that the frequency of the D allele was higher in poor CCC group than in the good CCC group (95% confidence interval [CI], 2.16-7.38; P < 0.001). Multiple regression analysis with CCC development as the dependent variable revealed that the presence of total occlusion of the left circumflex artery (95% CI, 1.29-6.6; P = 0.001), ACE DD genotype (95% CI, 2.55-12.79; P = 0.001), presence of diabetes (95% CI, 1.03-3.16; P = 0.005), and pulse pressure (95% CI, 1.04-1.56; P = 0.045) were independent determinants of poor coronary collateral development. This study showed that ACE DD polymorphism is associated with poor CCC. Poor collateral circulation in patients carrying the D allele may be associated with endothelial dysfunction and elevated blood ACE levels in these patients.

Adolescents and Young Adults with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia: Impact of Care at Specialized Cancer Centers on Survival Outcome.

PubMed

Wolfson, Julie; Sun, Can-Lan; Wyatt, Laura; Stock, Wendy; Bhatia, Smita

2017-03-01

Background: Adolescents and young adults (AYA; 15-39 years) with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) experience inferior survival when compared with children. Impact of care at NCI-designated Comprehensive Cancer Centers (CCC) or Children's Oncology Group sites (COG) on survival disparities remains unstudied. Methods: Using the Los Angeles cancer registry, we identified 1,870 ALL or AML patients between 1 and 39 years at diagnosis. Cox regression analyses assessed risk of mortality; younger age + CCC/COG served as the referent group. Logistic regression was used to determine odds of care at CCC/COG, adjusting for variables above. Results: ALL outcome: AYAs at non-CCC/COG experienced inferior survival (15-21 years: HR = 1.9, P = 0.005; 22-29 years: HR = 2.6, P < 0.001; 30-39 years: HR = 3.0, P < 0.001). Outcome at CCC/COG was comparable between children and young AYAs (15-21 years: HR = 1.3, P = 0.3; 22-29 years: HR = 1.2, P = 0.2) but was inferior for 30- to 39-year-olds (HR = 3.4, P < 0.001). AML outcome: AYAs at non-CCC/COG experienced inferior outcome (15-21 years: HR = 1.8, P = 0.02; 22-39 years: HR = 1.4, P = 0.06). Outcome at CCC/COG was comparable between children and 15- to 21-year-olds (HR = 1.3, P = 0.4) but was inferior for 22- to 39-year-olds (HR = 1.7, P = 0.05). Access: 15- to 21-year-olds were less likely to use CCC/COG than children ( P < 0.001). In 22- to 39-year-olds, public/uninsured (ALL: P = 0.004; AML<0.001), African American/Hispanics (ALL: P = 0.03), and 30- to 39-year-olds (ALL: P = 0.03) were less likely to use CCC/COG. Conclusions: Poor survival in AYAs with ALL and AML is mitigated by care at CCC/COG. Barriers to CCC/COG care include public/uninsured, and African American/Hispanic race/ethnicity. Impact: Care at CCC/COG explains, in part, inferior outcomes in AYAs with ALL and AML. Key sociodemographic factors serve as barriers to care at specialized centers. Cancer Epidemiol Biomarkers Prev; 26(3); 312-20. ©2017 AACR . ©2017 American Association for Cancer Research.

The relationship of plasma decoy receptor 3 and coronary collateral circulation in patients with coronary artery disease.

PubMed

Yan, Youyou; Song, Dandan; Liu, Lulu; Meng, Xiuping; Qi, Chao; Wang, Junnan

2017-11-15

Previously, decoy receptor 3 (DcR3) was found to be a potential angiogenetic factor, while the relationship of DcR3 with coronary collateral circulation formation has not been investigated. In this study, we aimed to investigate whether plasma decoy receptor 3 levels was associated with CCC formation and evaluate its predictive power for CCC status in patients with coronary artery disease. Among patients who underwent coronary angiography with coronary artery disease and had a stenosis of ≥90% were included in our study. Collateral degree was graded according to Rentrope Cohen classification. Patients with grade 2 or 3 collateral degree were enrolled in good CCC group and patients with grade 0 or 1 collateral degree were enrolled in poor CCC group. Plasma DcR3 level was significantly higher in good CCC group (328.00±230.82 vs 194.84±130.63ng/l, p<0.01) and positively correlated with Rentrope grade (p<0.01). In addition, plasma DcR3 was also positively correlated with VEGF-A. Both ROC (receiver operating characteristic curve) and multinomial logistical regression analysis showed that plasma DcR3 displayed potent predictive power for CCC status. Higher plasma DcR3 level was related to better CCC formation and displayed potent predictive power for CCC status. Copyright © 2017. Published by Elsevier Inc.

Genetic and Biochemical Analysis of High Iron Toxicity in Yeast

PubMed Central

Lin, Huilan; Li, Liangtao; Jia, Xuan; Ward, Diane McVey; Kaplan, Jerry

2011-01-01

Iron storage in yeast requires the activity of the vacuolar iron transporter Ccc1. Yeast with an intact CCC1 are resistant to iron toxicity, but deletion of CCC1 renders yeast susceptible to iron toxicity. We used genetic and biochemical analysis to identify suppressors of high iron toxicity in Δccc1 cells to probe the mechanism of high iron toxicity. All genes identified as suppressors of high iron toxicity in aerobically grown Δccc1 cells encode organelle iron transporters including mitochondrial iron transporters MRS3, MRS4, and RIM2. Overexpression of MRS3 suppressed high iron toxicity by decreasing cytosolic iron through mitochondrial iron accumulation. Under anaerobic conditions, Δccc1 cells were still sensitive to high iron toxicity, but overexpression of MRS3 did not suppress iron toxicity and did not result in mitochondrial iron accumulation. We conclude that Mrs3/Mrs4 can sequester iron within mitochondria under aerobic conditions but not anaerobic conditions. We show that iron toxicity in Δccc1 cells occurred under both aerobic and anaerobic conditions. Microarray analysis showed no evidence of oxidative damage under anaerobic conditions, suggesting that iron toxicity may not be solely due to oxidative damage. Deletion of TSA1, which encodes a peroxiredoxin, exacerbated iron toxicity in Δccc1 cells under both aerobic and anaerobic conditions, suggesting a unique role for Tsa1 in iron toxicity. PMID:21115478

A model of the interfacial processes inhibiting the environmental degradation of Al-Cu alloys

NASA Astrophysics Data System (ADS)

Kearns, Jeffery Robert

A better understanding of the composition and structure of chemically treated Al alloy surfaces is necessary to devise new, more environmentally benign, coating systems for aircraft. In this work, the surface of AA2024-T3, as well as analogs for constituent intermetallic compounds (IMC), were examined at various stages of the Al alloy pretreatment and chromate conversion coating (CCC) process. A complement of techniques were used: imaging and dyanmic Secondary Ion Mass Spectroscopy (SIMS), Variable-Angle X-ray Photoelectron Spectroscopy (VA/XPS), Synchrotron Infrared Microspectroscopy (SIRS), X-ray Absorption Spectroscopy (XAS), and Electrochemical Impedance Spectroscopy (EIS). The water and hydrocarbons in commercial CCC destabilized Cr(VI) during exposure to soft x-rays. However, it was possible to prevent photochemical reduction with the ultra-clean vacuum pumping practice recently developed at Stony Brook. The type of pretreatment used prior to chromate conversion coating influenced the extent of IMC removal, Cu (re)distribution, and surface activity. Cu(I) was observed on all the chemically treated surfaces. Samples pretreated in Sanchem 1000 while galvanically coupled to a Pt mesh had a more desirable distribution of Cu for subsequent processing. Chromate reduction was not a significant factor in CCC aging over a 24-hr period, but surface dehydration and structural change were correlated and causative. Imaging SIMS revealed heterogeneities in the CCC that varied laterally with IMC in the alloy substrate. These regions were depleted in compounds containing Cr, F, and CN. Cu was found at localized sites in the CCC contact surface. Cyano groups were bound as Cr(IlI)-CNFe(H). The chromate available for CCC repair was located on matrix regions through the entire bulk of the CCC. The presence of residual contaminants (e.g. cleaning agents, metal working fluid, ink) affected the distribution of activator compounds (e.g. ferricyanide) in a CCC. The cyanide complex (Cr(Ill)-Fe-CN6) was found in the CCC bulk not just at the outermost surface. A new model for CCC on Al-Cr alloys is proposed. The model is based on the sol-gel-like nascent CCC that limits the transport of IMC dissolution products.

Development of an efficient fractionation method for the preparative separation of sesquiterpenoids from Tussilago farfara by counter-current chromatography.

PubMed

Song, Kwangho; Lee, Kyoung Jin; Kim, Yeong Shik

2017-03-17

A novel application of counter-current chromatography (CCC) to enrich plant extracts using direct and continuous injection (CCC-DCI) was developed to fractionate sesquiterpenoids from the buds of Tussilago farfara L. In this study, an n-hexane-acetonitrile-water (HAcW) solvent system was separately pumped into the CCC column, and an extraction solution (45% acetonitrile) was directly and continuously injected into the CCC column. Since the extraction solution was used as a mobile phase in this method, solvent consumption could be greatly reduced. To enrich the extraction solution (315.9g/5.4L), only 4.2L water, 4.6L acetonitrile, and 1.2L n-hexane were used, including the extraction step. Finally, 6.8g of a sesquiterpenoid-enriched (STE) fraction was obtained from the crude extract (315.9g) of Tussilago farfara (1kg) in a single CCC run with a separation time of 8.5h. The sample injection capacity of CCC-DCI was greater than 300g; this amount of sample could not be handled in conventional CCC or other fractionation methods with the same column volume. Moreover, three major sesquiterpenoids (1: tussilagone, 2: 14-acetoxy-7β-(3'-ethyl cis-crotonoyloxy)-1α-(2'-methylburyryloxy)-notonipetranone, and 3: 7β-(3'-ethyl cis-crotonoyloxy)-1α-(2'-methylburyryloxy)-3, 14-dehydro-Z-notonipetranone) were purified from the STE fraction by CCC, and their chemical structures were elucidated by 1 H NMR and 13 C NMR. A quantification study was conducted, and the contents of compounds 1-3 in the CCC-DCI fraction were higher than those of conventional multi-step fractionations performed in series: solvent partitioning and open column chromatography. Furthermore, the average CCC-DCI recoveries were 96.1% (1), 96.9% (2), and 94.6% (3), whereas the open column chromatography recoveries were 77.7% (1), 66.5% (2), and 58.4% (3). The developed method demonstrates that CCC is a useful technique for enriching target components from natural products. Copyright © 2017 Elsevier B.V. All rights reserved.

101. Catalog HHistory 1, C.C.C., 34 Landscaping, Negative No. 1340 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

101. Catalog H-History 1, C.C.C., 34 Landscaping, Negative No. 1340 (Photographer and date unknown) BANK BLENDING WORK BY CCC. - Skyline Drive, From Front Royal, VA to Rockfish Gap, VA , Luray, Page County, VA

[Dynamic detection of duck hepatitis B virus cccDNA in serum of ducks with liver injury].

PubMed

Zhao, Ke-kai; Wang, Qing; Miao, Xiao-hui; Xu, Wen-sheng

2010-09-21

To confirm whether DHBV cccDNA could be detected in serum of DHBV-infected ducks after liver injury. Twenty four ducks with persistent DHBV infection were divided into 4 groups with the following treatments: A, D-galactosamine (D-GalN, 2.2 g/kg) and lipopolysaccharide (LPS, 100 µg/kg); B, 10 mg/kg of carbon tetrachloride (CCl4) every 12 h twice following D-GalN and LPS; C, 15 mg/kg of CCl4 every 12 h twice following D-GalN and LPS; D, normal saline as normal control (NC). At 0 h, 24 h, 36 h and 48 h post-treatment, sera were collected from each duck for determination of serum DHBV load, DHBV cccDNA and alanine aminotransferase (ALT). And ducks were eventually sacrificed to obtain liver specimens for pathological assessment of liver lesions and determination of intrahepatic total DHBV DNA and DHBV cccDNA. (1) No obvious pathological change was observed in the liver of ducks from NC group while the indices of liver injury were significantly different between Groups A, B and C; (2) DHBV cccDNA was undetectable in the sera of ducks from NC and A group at all time points. In contrast, DHBV cccDNA, varying from 3.17 × 10(3) copies/ml to 1.72 × 10(4) copies/ml, was detected in the sera of 2 ducks from Group B and 3 ducks from Group C at 36 h post-treatment. The occurrence of DHBV cccDNA in serum was significantly correlated with the degree of liver injury while no significant association with serum ALT level and DHBV load as well as with the level of intrahepatic total DHBV DNA and DHBV cccDNA was observed. DHBV cccDNA may be detected in the serum when the liver of duck is seriously damaged. The incidence of DHBV cccDNA occurrence in the serum is significantly associated with the severity of liver injury.

Toward an understanding of the pathophysiology of clear cell carcinoma of the ovary (Review)

PubMed Central

UEKURI, CHIHARU; SHIGETOMI, HIROSHI; ONO, SUMIRE; SASAKI, YOSHIKAZU; MATSUURA, MIYUKI; KOBAYASHI, HIROSHI

2013-01-01

Endometriosis-associated ovarian cancers demonstrate substantial morphological and genetic diversity. The transcription factor, hepatocyte nuclear factor (HNF)-1β, may be one of several key genes involved in the identity of ovarian clear cell carcinoma (CCC). The present study reviews a considerably expanded set of HNF-1β-associated genes and proteins that determine the pathophysiology of CCC. The current literature was reviewed by searching MEDLINE/PubMed. Functional interpretations of gene expression profiling in CCC are provided. Several important CCC-related genes overlap with those known to be regulated by the upregulation of HNF-1β expression, along with a lack of estrogen receptor (ER) expression. Furthermore, the genetic expression pattern in CCC resembles that of the Arias-Stella reaction, decidualization and placentation. HNF-1β regulates a subset of progesterone target genes. HNF-1β may also act as a modulator of female reproduction, playing a role in endometrial regeneration, differentiation, decidualization, glycogen synthesis, detoxification, cell cycle regulation, implantation, uterine receptivity and a successful pregnancy. In conclusion, the present study focused on reviewing the aberrant expression of CCC-specific genes and provided an update on the pathological implications and molecular functions of well-characterized CCC-specific genes. PMID:24179489

7 CFR 1412.34 - Submitting production evidence for establishing direct payment yields for oilseeds and pulse crops.

Code of Federal Regulations, 2010 CFR

2010-01-01

... in such manner as required by CCC on a CCC-approved standard, uniform form designated by CCC. (b)(1... furnish documentary evidence in order to verify the information provided on the report of production...

100. Catalog HHistory 1, C.C.C., 34 Landscaping, Negative No. P ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

100. Catalog H-History 1, C.C.C., 34 Landscaping, Negative No. P 733c (Photographer and date unknown) SLOPE MAINTENANCE WORK BY CCC. - Skyline Drive, From Front Royal, VA to Rockfish Gap, VA , Luray, Page County, VA

7 CFR 1493.1 - General statement.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS Restrictions and Criteria for Export Credit... use of credit guarantees under the Commodity Credit Corporation (CCC) Export Credit Guarantee Program (GSM-102) and the Intermediate Credit Guarantee Program (GSM-103) and the criteria considered by CCC in...

7 CFR 1493.1 - General statement.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS Restrictions and... restrictions which apply to the use of credit guarantees under the Commodity Credit Corporation (CCC) Export... criteria considered by CCC in determining the annual allocations of credit guarantees to be made available...

7 CFR 1493.1 - General statement.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS Restrictions and Criteria for Export Credit... use of credit guarantees under the Commodity Credit Corporation (CCC) Export Credit Guarantee Program (GSM-102) and the Intermediate Credit Guarantee Program (GSM-103) and the criteria considered by CCC in...

7 CFR 1493.1 - General statement.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS Restrictions and... restrictions which apply to the use of credit guarantees under the Commodity Credit Corporation (CCC) Export... criteria considered by CCC in determining the annual allocations of credit guarantees to be made available...

75 FR 81232 - Council Coordination Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-27

... meeting of the Council Coordination Committee (CCC), consisting of the Regional Fishery Management Council... Management Reauthorization Act (MSRA) of 2006 established the Council Coordination Committee (CCC) by... provide reports to the CCC for its information and discussion. All sessions are open to the public...

7 CFR 1493.1 - General statement.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS Restrictions and Criteria for Export Credit... use of credit guarantees under the Commodity Credit Corporation (CCC) Export Credit Guarantee Program (GSM-102) and the Intermediate Credit Guarantee Program (GSM-103) and the criteria considered by CCC in...

Treatment of Social Competence in Military Veterans, Service Members, and Civilians with Traumatic Brain Injury

DTIC Science & Technology

2015-08-01

Morey, MA, CCC- SLP 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING...Competence Problems after Traumatic Brain Injury: a Civilian and Military/Veteran Cohort Authors: Clare Morey, MA, CCC- SLP Lenore Hawley, MSSW, LCSW...Jody Newman, MA, CCC- SLP Angela Philippus, BA Cynthia Braden, MA, CCC- SLP Melissa Hofmann, MSPT Cynthia Harrison-Felix, PhD Please direct all

Closed-Form 3-D Localization for Single Source in Uniform Circular Array with a Center Sensor

NASA Astrophysics Data System (ADS)

Bae, Eun-Hyon; Lee, Kyun-Kyung

A novel closed-form algorithm is presented for estimating the 3-D location (azimuth angle, elevation angle, and range) of a single source in a uniform circular array (UCA) with a center sensor. Based on the centrosymmetry of the UCA and noncircularity of the source, the proposed algorithm decouples and estimates the 2-D direction of arrival (DOA), i.e. azimuth and elevation angles, and then estimates the range of the source. Notwithstanding a low computational complexity, the proposed algorithm provides an estimation performance close to that of the benchmark estimator 3-D MUSIC.

Molecular Analysis of Mixed Endometrial Carcinomas Shows Clonality in Most Cases.

PubMed

Köbel, Martin; Meng, Bo; Hoang, Lien N; Almadani, Noorah; Li, Xiaodong; Soslow, Robert A; Gilks, C Blake; Lee, Cheng-Han

2016-02-01

Mixed endometrial carcinoma refers to a tumor that comprises 2 or more distinct histotypes. We studied 18 mixed-type endometrial carcinomas-11 mixed serous and low-grade endometrioid carcinomas (SC/EC), 5 mixed clear cell and low-grade ECs (CCC/EC), and 2 mixed CCC and SCs (CCC/SC), using targeted next-generation sequencing and immunohistochemistry to compare the molecular profiles of the different histotypes present in each case. In 16 of 18 cases there was molecular evidence that both components shared a clonal origin. Eight cases (6 EC/SC, 1 EC/CCC, and 1 SC/CCC) showed an SC molecular profile that was the same in both components. Five cases (3 CCC/EC and 2 SC/EC) showed a shared endometrioid molecular profile and identical mismatch-repair protein deficiency in both components. A single SC/EC case harbored the same POLE exonuclease domain mutation in both components. One SC/CCC and 1 EC/CCC case showed both shared and unique molecular features in the 2 histotype components, suggesting early molecular divergence from a common clonal origin. In 2 cases, there were no shared molecular features, and these appear to be biologically unrelated synchronous tumors. Overall, these results show that the different histologic components in mixed endometrial carcinomas typically share the same molecular aberrations. Mixed endometrial carcinomas most commonly occur through morphologic mimicry, whereby tumors with serous-type molecular profile show morphologic features of EC or CCC, or through underlying deficiency in DNA nucleotide repair, with resulting rapid accrual of mutations and intratumoral phenotypic heterogeneity. Less commonly, mixed endometrial carcinomas are the result of early molecular divergence from a common progenitor clone or are synchronous biologically unrelated tumors (collision tumors).

Multiple injection mode with or without repeated sample injections: Strategies to enhance productivity in countercurrent chromatography.

PubMed

Müller, Marco; Wasmer, Katharina; Vetter, Walter

2018-06-29

Countercurrent chromatography (CCC) is an all liquid based separation technique typically used for the isolation and purification of natural compounds. The simplicity of the method makes it easy to scale up CCC separations from analytical to preparative and even industrial scale. However, scale-up of CCC separations requires two different instruments with varying coil dimensions. Here we developed two variants of the CCC multiple injection mode as an alternative to increase the throughput and enhance productivity of a CCC separation when using only one instrument. The concept is based on the parallel injection of samples at different points in the CCC column system and the simultaneous separation using one pump only. The wiring of the CCC setup was modified by the insertion of a 6-port selection valve, multiple T-pieces and sample loops. Furthermore, the introduction of storage sample loops enabled the CCC system to be used with repeated injection cycles. Setup and advantages of both multiple injection modes were shown by the isolation of the furan fatty acid 11-(3,4-dimethyl-5-pentylfuran-2-yl)-undecanoic acid (11D5-EE) from an ethyl ester oil rich in 4,7,10,13,16,19-docosahexaenoic acid (DHA-EE). 11D5-EE was enriched in one step from 1.9% to 99% purity. The solvent consumption per isolated amount of analyte could be reduced by ∼40% compared to increased throughput CCC and by ∼5% in the repeated multiple injection mode which also facilitated the isolation of the major compound (DHA-EE) in the sample. Copyright © 2018 Elsevier B.V. All rights reserved.

A cohort study of cardiac resynchronization therapy in patients with chronic Chagas cardiomyopathy.

PubMed

Martinelli Filho, Martino; de Lima Peixoto, Giselle; de Siqueira, Sérgio Freitas; Martins, Sérgio Augusto Mezzalira; Nishioka, Silvana Angelina D'ório; Pedrosa, Anísio Alexandre Andrade; Teixeira, Ricardo Alkmim; Dos Santos, Johnny Xavier; Costa, Roberto; Kalil Filho, Roberto; Ramires, José Antônio Franchini

2018-03-02

Cardiac resynchronization therapy (CRT) is an established procedure for patients with heart failure. However, trials evaluating its efficacy did not include patients with chronic Chagas cardiomyopathy (CCC). We aimed to assess the role of CRT in a cohort of patients with CCC. This retrospective study compared the outcomes of CCC patients who underwent CRT with those of dilated (DCM) and ischaemic cardiomyopathies (ICM). The primary endpoint was all-cause mortality and the secondary endpoints were the rate of non-advanced New York Heart Association (NYHA) class 12 months after CRT and echocardiographic changes evaluated at least 6 months after CRT. There were 115 patients in the CCC group, 177 with DCM, and 134 with ICM. The annual mortality rates were 25.4%, 10.4%, and 11.3%, respectively (P < 0.001). Multivariate analysis adjusted for potential confounders showed that the CCC group had a two-fold [hazard ratio 2.34 (1.47-3.71), P < 0.001] higher risk of death compared to the DCM group. The rate of non-advanced NYHA class 12 months after CRT was significantly higher in non-CCC groups than in the CCC group (DCM 74.0% vs. ICM 73.9% vs. 56.5%, P < 0.001). Chronic Chagas cardiomyopathy and ICM patients had no improvement in the echocardiographic evaluation, but patients in the DCM group had an increase in left ventricular ejection fraction and a decrease in left ventricular end-diastolic diameter. This study showed that CCC patients submitted to CRT have worse prognosis compared to patients with DCM and ICM who undergo CRT. Studies comparing CCC patients with and without CRT are warranted.

Demographic, Clinical, and Prognostic Factors of Ovarian Clear Cell Adenocarcinomas According to Endometriosis Status.

PubMed

Schnack, Tine H; Høgdall, Estrid; Thomsen, Lotte Nedergaard; Høgdall, Claus

2017-11-01

Women with endometriosis carry an increased risk for ovarian clear cell adenocarcinomas (CCCs). Clear cell adenocarcinoma may develop from endometriosis lesions. Few studies have compared clinical and prognostic factors and overall survival in patients diagnosed as having CCC according to endometriosis status. Population-based prospectively collected data on CCC with coexisting pelvic (including ovarian; n = 80) and ovarian (n = 46) endometriosis or without endometriosis (n = 95) were obtained through the Danish Gynecological Cancer Database. χ Test, independent-samples t test, logistic regression, Kaplan-Meier test, and Cox regression were used. Statistical tests were 2 sided. P values less than 0.05 were considered statistically significant. Patients with CCC and pelvic or ovarian endometriosis were significantly younger than CCC patients without endometriosis, and a higher proportion of them were nulliparous (28% and 31% vs 17% (P = 0.07 and P = 0.09). Accordingly, a significantly higher proportion of women without endometriosis had given birth to more than 1 child. Interestingly, a significantly higher proportion of patients with ovarian endometriosis had pure CCCs (97.8% vs 82.1%; P = 0.001) as compared with patients without endometriosis. Overall survival was poorer among CCC patients with concomitant ovarian endometriosis (hazard ratio, 2.56 [95% confidence interval, 1.29-5.02], in the multivariate analysis. Age at CCC diagnosis and parity as well as histology differ between CCC patients with and without concomitant endometriosis. Furthermore, CCC patients with concomitant ovarian endometriosis have a poorer prognosis compared with endometriosis-negative CCC patients. These differences warrant further research to determine whether CCCs with and without concomitant endometriosis develop through distinct pathogenic pathways.

Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma

PubMed Central

Arakawa, Noriaki; Kobayashi, Hiroshi; Yonemoto, Naohiro; Masuishi, Yusuke; Ino, Yoko; Shigetomi, Hiroshi; Furukawa, Naoto; Ohtake, Norihisa; Miyagi, Yohei; Hirahara, Fumiki; Hirano, Hisashi; Miyagi, Etsuko

2016-01-01

Background There is currently no reliable serum biomarker for ovarian clear cell carcinoma (CCC), a highly lethal histological subtype of epithelial ovarian cancer (EOC). Previously, using a proteome-based approach, we identified tissue factor pathway inhibitor 2 (TFPI2) as a candidate serum biomarker for CCC. In this study, we sought to evaluate the clinical diagnostic performance of TFPI2 in preoperative prediction of CCC. Methods Serum TFPI2 levels were measured in serum samples from a retrospective training set consisting of patients with benign and borderline ovarian tumors, EOC subtypes, and uterine diseases. Via receiver operating characteristic (ROC) analyses, we compared the diagnostic performance of TFPI2 with that of CA125 in discrimination of patients with ovarian CCC from other patient groups. The observed diagnostic performances were examined in a prospective validation set. Results The 268-patient training set included 29 patients with ovarian CCC. Unlike CA125, which was also elevated in patients with endometriosis and several EOC subtypes, serum TFPI2 levels were specifically elevated only in ovarian CCC patients, consistent with the mRNA expression pattern in tumor tissues. The area under the ROC curve (AUC) of serum TFPI2 was obviously higher than that of CA125 for discrimination of CCC from other ovarian diseases (AUC = 0.891 versus 0.595). Applying a cut-off value of 280 pg/mL, TFPI2 could distinguish early-stage (FIGO I and II) CCC from endometriosis with 72.2% sensitivity, 93.3% specificity, and 88.8% accuracy. Similar results were confirmed in an independent 156-patient prospective validation set. Conclusions TFPI2 is a useful serum biomarker for preoperative clinical diagnosis of CCC. PMID:27798689

Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma.

PubMed

Arakawa, Noriaki; Kobayashi, Hiroshi; Yonemoto, Naohiro; Masuishi, Yusuke; Ino, Yoko; Shigetomi, Hiroshi; Furukawa, Naoto; Ohtake, Norihisa; Miyagi, Yohei; Hirahara, Fumiki; Hirano, Hisashi; Miyagi, Etsuko

2016-01-01

There is currently no reliable serum biomarker for ovarian clear cell carcinoma (CCC), a highly lethal histological subtype of epithelial ovarian cancer (EOC). Previously, using a proteome-based approach, we identified tissue factor pathway inhibitor 2 (TFPI2) as a candidate serum biomarker for CCC. In this study, we sought to evaluate the clinical diagnostic performance of TFPI2 in preoperative prediction of CCC. Serum TFPI2 levels were measured in serum samples from a retrospective training set consisting of patients with benign and borderline ovarian tumors, EOC subtypes, and uterine diseases. Via receiver operating characteristic (ROC) analyses, we compared the diagnostic performance of TFPI2 with that of CA125 in discrimination of patients with ovarian CCC from other patient groups. The observed diagnostic performances were examined in a prospective validation set. The 268-patient training set included 29 patients with ovarian CCC. Unlike CA125, which was also elevated in patients with endometriosis and several EOC subtypes, serum TFPI2 levels were specifically elevated only in ovarian CCC patients, consistent with the mRNA expression pattern in tumor tissues. The area under the ROC curve (AUC) of serum TFPI2 was obviously higher than that of CA125 for discrimination of CCC from other ovarian diseases (AUC = 0.891 versus 0.595). Applying a cut-off value of 280 pg/mL, TFPI2 could distinguish early-stage (FIGO I and II) CCC from endometriosis with 72.2% sensitivity, 93.3% specificity, and 88.8% accuracy. Similar results were confirmed in an independent 156-patient prospective validation set. TFPI2 is a useful serum biomarker for preoperative clinical diagnosis of CCC.

Clear cell carcinomas of the ovary have poorer outcomes compared with serous carcinomas: Results from a single-center Taiwanese study.

PubMed

Ku, Fei-Chun; Wu, Ren-Chin; Yang, Lan-Yan; Tang, Yun-Hsin; Chang, Wei-Yang; Yang, Jung-Erh; Wang, Chun-Chieh; Jung, Shih-Ming; Lin, Cheng-Tao; Chang, Ting-Chang; Chao, Angel; Lai, Chyong-Huey

2018-02-01

To compare the clinical outcomes of Taiwanese patients with ovarian clear cell carcinomas (CCCs) and serous carcinomas (SCs). We retrieved the clinical records of women with epithelial ovarian cancer (Stage I-IV) who received primary surgeries between 2000 and 2013. Cancer-specific survival (CSS), progression-free survival, and survival after recurrence (SAR) of CCC and SC patients were retrospectively compared. Multivariate analysis was used to identify the independent predictors of survival. Of 891 women diagnosed with epithelial ovarian cancer, 169 CCCs and 351 high-grade SCs were analyzed. The 5-year CSS rates of CCC patients were significantly lower than those of SC for both Stage III (22.3% vs. 47.3%, p = 0.001) and Stage IV (0% vs. 24.4%, p = 0.001) disease. In the absence of gross residual malignancies, the 5-year CSS rate was better for CCC (82.3%) than SC (75.2%, p = 0.010). The 5-year SAR rate was significantly lower for CCC than SC (14.3% vs. 24.4%, p = 0.002). Old age and residual malignancies were independent prognostic factors for CSS in the entire cohort of CCC patients. In the subgroup of Stage I CCC, positive cytology was identified as the only adverse prognostic factor for CSS. The clinical outcomes of CCC are generally poorer than SC. Complete cytoreduction to no gross residual disease should be ideally achieved in CCC patients. A greater understanding of the molecular pathogenesis of CCC may lead to tailored therapies, ultimately optimizing outcomes. Copyright © 2017. Published by Elsevier B.V.

Pragmatics fragmented: the factor structure of the Dutch children's communication checklist (CCC).

PubMed

Geurts, Hilde M; Hartman, Catharina; Verté, Sylvie; Oosterlaan, Jaap; Roeyers, Herbert; Sergeant, Joseph A

2009-01-01

A number of disorders are associated with pragmatic difficulties. Instruments that can make subdivisions within the larger construct of pragmatics could be important tools for disentangling profiles of pragmatic difficulty in different disorders. The deficits underlying the observed pragmatic difficulties may be different for different disorders. To study the construct validity of a pragmatic language questionnaire. The construct of pragmatics is studied by applying exploratory factor analysis (EFA) and confirmatory factor analysis to the parent version of the Dutch Children's Communication Checklist (CCC; Bishop 1998 ). Parent ratings of 1589 typically developing children and 481 children with a clinical diagnosis were collected. Four different factor models derived from the original CCC scales and five different factor models based on EFA were compared with each other. The models were cross-validated. The EFA-derived models were substantively different from the originally proposed CCC factor structure. EFA models gave a slightly better fit than the models based on the original CCC scales, though neither provided a good fit to the parent data. Coherence seemed to be part of language form and not of pragmatics, which is in line with the adaptation of the CCC, the CCC-2 (Bishop 2003 ). Most pragmatic items clustered together in one factor and these pragmatic items also clustered with items related to social relationships and specific interests. The nine scales of the original CCC do not reflect the underlying factor structure. Therefore, scale composition may be improved on and scores on subscale level need to be interpreted cautiously. Therefore, in interpreting the CCC profiles, the overall measure might be more informative than the postulated subscales as more information is needed to determine which constructs the suggested subscales are actually measuring.

Ruthenium(II) carbonyl complexes bearing CCC-pincer bis-(carbene) ligands: synthesis, structures and activities toward recycle transfer hydrogenation reactions.

PubMed

Naziruddin, Abbas Raja; Huang, Zhao-Jiunn; Lai, Wei-Chih; Lin, Wan-Jung; Hwang, Wen-Shu

2013-09-28

A new series of ruthenium(II) carbonyl complexes with benzene-based CCC-pincer bis-(carbene) ligands, [((R)CCC(R))Ru(CO)2(X)](0/+) and [((R)CCC(R))Ru(CO)(NN)](+) ((R)CCC(R) = 2,6-bis-(1-alkylimidazolylidene)benzene, R = Me or (n)Bu; X = I, Br, CH3CN, or 6-(aminomethyl)pyridine (ampy); NN = 2·CH3CN, or chelating ampy or bipyridine), was synthesized and fully characterized. X-Ray structure determinations revealed that these eight complexes have pseudo-octahedral configurations around the ruthenium center with the pincer ligand occupying three meridional sites. These complexes prove to be efficient precatalysts demonstrating very good activity and reusability for the transfer hydrogenation of ketones.

7 CFR 1499.12 - Subrecipients.

Code of Federal Regulations, 2011 CFR

2011-01-01

... to the transfer of any donated commodities, sale proceeds, income or CCC-provided funds to the... any donated commodities, sale proceeds, income, or CCC-provided cash funds that are not used in... donated commodities, sale proceeds, income, or CCC-provided funds to the subrecipient. (c) The participant...

7 CFR 1493.80 - Evidence of export.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Evidence of export. 1493.80 Section 1493.80... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103...

7 CFR 1435.505 - Miscellaneous provisions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS SUGAR PROGRAM Processor Sugar Payment-In-Kind... acreage, desugarizing capacity or other measures of sugar production as CCC determines. (b) The contract... specified in the CCC production diversion contract. (c) CCC will transfer title of the sugar to the...