The manifold phospholipases A of Legionella pneumophila - identification, export, regulation, and their link to bacterial virulence.

PubMed

Banerji, Sangeeta; Aurass, Philipp; Flieger, Antje

2008-04-01

The intracellular lung pathogen Legionella pneumophila expresses secreted and cell-associated phospholipase A (PLA) and lysophospholipase A (LPLA) activities belonging to at least three enzyme families. The first family consists of three secreted PLA and LPLA activities displaying the amino acid signature motif 'GDSL'; PlaA, PlaC and PlaD. The second group contains the cell-associated and very potent PLA/LPLA, PlaB. The third group, the patatin-like proteins, comprises 11 members. One patatin-like protein, PatA/VipD, shows LPLA and PLA activities and interferes with vesicular trafficking when expressed in yeast and therefore is possibly involved in the intracellular infection process. Likewise, members of the first two phospholipase families have roles in bacterial virulence because phospholipases are important virulence factors that have been shown to promote bacterial survival, spread and host cell modification/damage. The GDSL enzyme PlaA detoxifies cytolytic lysophospholipids, and PlaB shows contact-dependent haemolytic activity. PlaC acylates cholesterol, a lipid present in eukaryotic hosts but not in the bacterium. Many of the L. pneumophila PLAs are exported by the type II Lsp or the type IVB Dot/Icm secretion systems involved in virulence factor export. Moreover, the regulation of lipolytic activities depends on the transcriptional regulators LetA/S and RpoS, inducing the expression of virulence traits, and on posttranscriptional activators like the zinc metalloprotease ProA.

Accurate prediction of bacterial type IV secreted effectors using amino acid composition and PSSM profiles.

PubMed

Zou, Lingyun; Nan, Chonghan; Hu, Fuquan

2013-12-15

Various human pathogens secret effector proteins into hosts cells via the type IV secretion system (T4SS). These proteins play important roles in the interaction between bacteria and hosts. Computational methods for T4SS effector prediction have been developed for screening experimental targets in several isolated bacterial species; however, widely applicable prediction approaches are still unavailable In this work, four types of distinctive features, namely, amino acid composition, dipeptide composition, .position-specific scoring matrix composition and auto covariance transformation of position-specific scoring matrix, were calculated from primary sequences. A classifier, T4EffPred, was developed using the support vector machine with these features and their different combinations for effector prediction. Various theoretical tests were performed in a newly established dataset, and the results were measured with four indexes. We demonstrated that T4EffPred can discriminate IVA and IVB effectors in benchmark datasets with positive rates of 76.7% and 89.7%, respectively. The overall accuracy of 95.9% shows that the present method is accurate for distinguishing the T4SS effector in unidentified sequences. A classifier ensemble was designed to synthesize all single classifiers. Notable performance improvement was observed using this ensemble system in benchmark tests. To demonstrate the model's application, a genome-scale prediction of effectors was performed in Bartonella henselae, an important zoonotic pathogen. A number of putative candidates were distinguished. A web server implementing the prediction method and the source code are both available at http://bioinfo.tmmu.edu.cn/T4EffPred.

Transcriptional activation of the tad type IVb pilus operon by PypB in Yersinia enterocolitica.

PubMed

Schilling, Jennifer; Wagner, Karin; Seekircher, Stephanie; Greune, Lilo; Humberg, Verena; Schmidt, M Alexander; Heusipp, Gerhard

2010-07-01

Type IV pili are virulence factors in various bacteria and mediate, among other functions, the colonization of diverse surfaces. Various subclasses of type IV pili have been identified, but information on pilus expression, biogenesis, and the associated phenotypes is sparse for the genus Yersinia. We recently described the identification of PypB as a transcriptional regulator in Yersinia enterocolitica. Here we show that the pypB gene is associated with the tad locus, a genomic island that is widespread among bacterial and archaeal species. The genetic linkage of pypB with the tad locus is conserved throughout the yersiniae but is not found among other bacteria carrying the tad locus. We show that the genes of the tad locus form an operon in Y. enterocolitica that is controlled by PypB and that pypB is part of this operon. The tad genes encode functions necessary for the biogenesis of the Flp subfamily of type IVb pili initially described for Aggregatibacter actinomycetemcomitans to mediate a tight-adherence phenotype. In Y. enterocolitica, the Flp pilin protein shows some peculiarities in its amino acid sequence that imply similarities as well as differences compared to typical motifs found in the Flp subtype of type IVb pili. Flp is expressed and processed after PypB overproduction, resulting in microcolony formation but not in increased adherence to biotic or abiotic surfaces. Our data describe the transcriptional regulation of the tad type IVb pilus operon by PypB in Y. enterocolitica but fail to show most previously described phenotypes associated with this type of pilus in other bacteria.

Apollo 9 Mission image - Top view of the Lunar Module (LM) spacecraft from the Command Module (CM)

NASA Image and Video Library

1969-03-03

The Lunar Module (LM) 3 "Spider",still attached to the Saturn V third (S-IVB) stage,is photographed from the Command/Service Module (CSM) "Gumdrop" on the first day of the Apollo 9 Earth-orbital mission. This picture was taken following CSM/LM-S-IVB separation,and prior to LM extraction from the S-IVB. The Spacecraft Lunar Module Adapter (SLA) panels have already been jettisoned. Film magazine was A,film type was SO-368 Ektachrome with 0.460 - 0.710 micrometers film / filter transmittance response and haze filter, 80mm lens.

Functional selection of a type IV pili-binding peptide that specifically inhibits Salmonella Typhi adhesion to/invasion of human monocytic cells.

PubMed

Wu, Hong-Yan; Zhang, Xiao-Lian; Pan, Qin; Wu, Jianguo

2005-11-01

Salmonella enterica serovar Typhi (S. Typhi) is an important pathogen which infects humans exclusively and causes typhoid or enteric fever. Recently it has been discovered that type IVB pili, encoded by the S. Typhi pil operon located in the major pathogenicity island, may be important in the pathogenesis of epidemic enteric fever. To further investigate the roles of type IVB pili of S. Typhi, a 12-mer peptide (RQERSSLSKPVV), binding to the structural protein PilS of the type IVB pili of S. Typhi, was isolated with a ribosome display system. This peptide was designated as peptide R. We found that peptide R inhibited adhesion to/invasion of human monocytic THP-1 cells by piliated S. Typhi bacteria, but had no effects on nonpiliated S. Typhi bacteria. A random 12-mer peptide, of size and solubility equal to peptide R, served as a control on the specificity of peptide R. The specific interaction and binding equilibrium between the 12-mer peptide R and PilS protein was determined by isothermal titration calorimetry (ITC) and a binding constant Ka determined to be between 0.4 x 10(5) and 2.2 x 10(5)L mol(-1). Our findings suggest that the type IV pili-binding peptide R holds potential as an antibacterial peptide effective against S. Typhi infections, both in terms of prevention and therapeutic treatment. The data further provide insights into the understanding of the pathogenic roles of the type IVB pili of S. Typhi.

Phospholipase PlaB is a new virulence factor of Legionella pneumophila.

PubMed

Schunder, Eva; Adam, Patrick; Higa, Futoshi; Remer, Katharina A; Lorenz, Udo; Bender, Jennifer; Schulz, Tino; Flieger, Antje; Steinert, Michael; Heuner, Klaus

2010-06-01

We previously identified Legionella pneumophila PlaB as the major cell-associated phospholipase A/lysophospholipase A with contact-dependent hemolytic activity. In this study, we further characterized this protein and found it to be involved in the virulence of L. pneumophila. PlaB was mainly expressed and active during exponential growth. Active PlaB was outer membrane-associated and at least in parts surface-exposed. Transport to the outer membrane was not dependent on the type I (T1SS), II (T2SS), IVB (T4BSS) or Tat secretion pathways. Furthermore, PlaB activity was not dependent on the presence of the macrophage infectivity potentiator (Mip) or the major secreted zinc metalloproteinase A (MspA). Despite the fact that PlaB is not essential for replication in protozoa or macrophage cell lines, we found that plaB mutants were impaired for replication in the lungs and dissemination to the spleen in the guinea pig infection model. Histological sections monitored less inflammation and destruction of the lung tissue after infection with the plaB mutants compared to L. pneumophila wild type. Taken together, PlaB is the first phospholipase A/lysophospholipase A with a confirmed role in the establishment of Legionnaires' disease. Copyright 2010 Elsevier GmbH. All rights reserved.

Icm/Dot-Independent Entry of Legionella pneumophila into Amoeba and Macrophage Hosts

PubMed Central

Bandyopadhyay, Purnima; Xiao, Huifang; Coleman, Hope A.; Price-Whelan, Alexa; Steinman, Howard M.

2004-01-01

Legionella pneumophila, the causative agent of Legionnaires' disease, expresses a type IVB secretion apparatus that translocates bacterial proteins into amoeba and macrophage hosts. When stationary-phase cultures are used to infect hosts, the type IVB apparatus encoded by the icm/dot genes is required for entry, delay of phagosome-lysosome fusion, and intracellular multiplication within host cells. Null mutants with mutations in icm/dot genes are defective in these phenotypes. Here a new model is described in which hosts are infected with stationary-phase cultures that have been incubated overnight in pH 6.5 buffer. This model is called Ers treatment because it enhances the resistance to acid, hydrogen peroxide, and antibiotic stress beyond that of stationary-phase cultures. Following Ers treatment entry into amoeba and macrophage hosts does not require dotA, which is essential for Legionella virulence phenotypes when hosts are infected with stationary-phase cultures, dotB, icmF, icmV, or icmX. Defective host entry is also suppressed for null mutants with mutations in the KatA and KatB catalase-peroxidase enzymes, which are required for proper intracellular growth in amoeba and macrophage hosts. Ers treatment-induced suppression of defective entry is not associated with increased bacterial adhesion to host cells or with morphological changes in the bacterial envelope but is dependent on protein expression during Ers treatment. By using proteomic analysis, Ers treatment was shown to induce a protein predicted to contain eight tetratricopeptide repeats, a motif previously implicated in enhanced entry of L. pneumophila. Characterization of Ers treatment-dependent changes in expression is proposed as an avenue for identifying icm/dot-independent factors that function in the entry of Legionella into amoeba and macrophage hosts. PMID:15271914

Organization and PprB-dependent control of the Pseudomonas aeruginosa tad Locus, involved in Flp pilus biology.

PubMed

Bernard, Christophe S; Bordi, Christophe; Termine, Elise; Filloux, Alain; de Bentzmann, Sophie

2009-03-01

Bacterial attachment to the substratum involves several cell surface organelles, including various types of pili. The Pseudomonas aeruginosa Tad machine assembles type IVb pili, which are required for adhesion to abiotic surfaces and to eukaryotic cells. Type IVb pili consist of a major subunit, the Flp pilin, processed by the FppA prepilin peptidase. In this study, we investigated the regulatory mechanism of the tad locus. We showed that the flp gene is expressed late in the stationary growth phase in aerobic conditions. We also showed that the tad locus was composed of five independent transcriptional units. We used transcriptional fusions to show that tad gene expression was positively controlled by the PprB response regulator. We subsequently showed that PprB bound to the promoter regions, directly controlling the expression of these genes. We then evaluated the contribution of two genes, tadF and rcpC, to type IVb pilus assembly. The deletion of these two genes had no effect on Flp production, pilus assembly, or Flp-mediated adhesion to abiotic surfaces in our conditions. However, our results suggest that the putative RcpC protein modifies the Flp pilin, thereby promoting Flp-dependent adhesion to eukaryotic cells.

Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer

ClinicalTrials.gov

2018-04-27

Extrahepatic Bile Duct Adenocarcinoma, Biliary Type; Gallbladder Adenocarcinoma, Biliary Type; Metastatic Pancreatic Adenocarcinoma; Recurrent Cholangiocarcinoma; Recurrent Gallbladder Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Intrahepatic Cholangiocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Gallbladder Cancer AJCC V7; Stage III Hepatocellular Carcinoma AJCC v7; Stage III Intrahepatic Cholangiocarcinoma AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IIIA Gallbladder Cancer AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Gallbladder Cancer AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Gallbladder Cancer AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IVA Gallbladder Cancer AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVA Intrahepatic Cholangiocarcinoma AJCC v7; Stage IVB Gallbladder Cancer AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7; Stage IVB Intrahepatic Cholangiocarcinoma AJCC v7; Unresectable Gallbladder Carcinoma; Unresectable Pancreatic Carcinoma

77 FR 9883 - Tribal Consultation Meetings Regarding Requirements Applicable to Title IV-B Child and Family...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-21

... Tribal Consultation Meetings Regarding Requirements Applicable to Title IV-B Child and Family Services...: Notice of tribal consultation. SUMMARY: The title IV-B regulations regarding the title IV-B plan and... title IV-B, subpart 1 and/or title IV-B, subpart 2 program and any other interested party. We provide...

Emergence of community-acquired methicillin-resistant Staphylococcus aureus in an Iranian referral paediatric hospital.

PubMed

Mamishi, S; Mahmoudi, S; Bahador, A; Matini, H; Movahedi, Z; Sadeghi, R H; Pourakbari, B

2015-01-01

The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals has been changed in recent years due to the arrival of community-associated MRSA (CA-MRSA) strains into healthcare settings. The aim of this study is to investigate the distribution of staphylococcal cassette chromosome mec (SCCmec) type V as well as SCCmec IV subtypes, which have been associated with community-acquired infection among healthcare-associated MRSA (HA-MRSA) isolates. Antimicrobial susceptibility, SCCmec type, spa type and the presence of Panton-Valentine leukocidin (PVL) genes were determined for all HA-MRSA isolates in an Iranian referral hospital. In this study of 48 HA-MRSA isolates, 13 (27%), three (6.2%), five (10.4%) and one (2%) belonged to SCCmec subtypes IVa, IVb, IVc and IVd, respectively. Only two isolates (4.2%) belonged to SCCmec types V Notably, one isolate was found to harbour concurrent SCCmec subtypes IVb and IVd. MRSA containing SCCmec subtype IVb, IVc and IVd as well as type V isolates were all susceptible to chloramphenicol, clindamycin and rifampicin, while the sensitivity to these antibiotics was lower among MRSA containing SCCmec subtype IVa. The most frequently observed spa ttype was t037, accounting for 88% (22/25). Three other spa type was t002, t1816 and t4478. Large reservoirs of MRSA containing type IV subtypes and type V now exist in patients in this Iranian hospital. Therefore, effective infection control management in order to control the spread of CA-MRSA is highly recommended.

In vivo and in vitro phenotypic differences between Great Lakes VHSV genotype IVb isolates with sequence types vcG001 and vcG002

PubMed Central

Imanse, Sierra M.; Cornwell, Emily R.; Getchell, Rodman G.; Kurath, Gael; Bowser, Paul R.

2014-01-01

Viral hemorrhagic septicemia virus (VHSV) is an aquatic rhabdovirus first recognized in farmed rainbow trout in Denmark. In the past decade, a new genotype of this virus, IVb was discovered in the Laurentian Great Lakes basin and has caused several massive die-offs in some of the 28 species of susceptible North American freshwater fishes. Since its colonization of the Great Lakes, several closely related sequence types within genotype IVb have been reported, the two most common of which are vcG001 and vcG002. These sequence types have different spatial distributions in the Great Lakes. The aim of this study was to determine whether the genotypic differences between representative vcG001 (isolate MI03) and vcG002 (isolate 2010-030 #91) isolates correspond to phenotypic differences in terms of virulence using both an in vitro and in vivo approach. In vitro infection of epithelioma papulosum cyprini (EPC), bluegill fry (BF-2), and Chinook salmon embryo (CHSE) cells demonstrated some differences in onset and rate of growth in EPC and BF-2 cells, without any difference in the quantity of RNA produced. In vivo infection of round gobies (Neogobius melanostomus) via immersion exposure to different concentrations of vcG001 or vcG002 caused a significantly greater mortality in round gobies exposed to 102 plaque forming units ml−1 of vcG001. These experiments suggest that there are phenotypic differences between Great Lakes isolates of VHSV genotype IVb. PMID:25722533

In vivo and in vitro phenotypic differences between Great Lakes VHSV genotype IVb isolates with sequence types vcG001 and vcG002

USGS Publications Warehouse

Imanse, Sierra M.; Cornwell, Emily R.; Getchell, Rodman G.; Kurath, Gael; Bowser, Paul R.

2014-01-01

Viral hemorrhagic septicemia virus (VHSV) is an aquatic rhabdovirus first recognized in farmed rainbow trout in Denmark. In the past decade, a new genotype of this virus, IVb was discovered in the Laurentian Great Lakes basin and has caused several massive die-offs in some of the 28 species of susceptible North American freshwater fishes. Since its colonization of the Great Lakes, several closely related sequence types within genotype IVb have been reported, the two most common of which are vcG001 and vcG002. These sequence types have different spatial distributions in the Great Lakes. The aim of this study was to determine whether the genotypic differences between representative vcG001 (isolate MI03) and vcG002 (isolate 2010-030 #91) isolates correspond to phenotypic differences in terms of virulence using both in vitro and in vivo approaches. In vitro infection of epithelioma papulosum cyprini (EPC), bluegill fry (BF-2), and Chinook salmon embryo (CHSE) cells demonstrated some differences in onset and rate of growth in EPC and BF-2 cells, without any difference in the quantity of RNA produced. In vivo infection of round gobies (Neogobius melanostomus) via immersion exposure to different concentrations of vcG001 or vcG002 caused a significantly greater mortality in round gobies exposed to 102 plaque forming units ml− 1 of vcG001. These experiments suggest that there are phenotypic differences between Great Lakes isolates of VHSV genotype IVb.

Spatiotemporal regulation of a Legionella pneumophila T4SS substrate by the metaeffector SidJ.

PubMed

Jeong, Kwang Cheol; Sexton, Jessica A; Vogel, Joseph P

2015-03-01

Modulation of host cell function is vital for intracellular pathogens to survive and replicate within host cells. Most commonly, these pathogens utilize specialized secretion systems to inject substrates (also called effector proteins) that function as toxins within host cells. Since it would be detrimental for an intracellular pathogen to immediately kill its host cell, it is essential that secreted toxins be inactivated or degraded after they have served their purpose. The pathogen Legionella pneumophila represents an ideal system to study interactions between toxins as it survives within host cells for approximately a day and its Dot/Icm type IVB secretion system (T4SS) injects a vast number of toxins. Previously we reported that the Dot/Icm substrates SidE, SdeA, SdeB, and SdeC (known as the SidE family of effectors) are secreted into host cells, where they localize to the cytoplasmic face of the Legionella containing vacuole (LCV) in the early stages of infection. SidJ, another effector that is unrelated to the SidE family, is also encoded in the sdeC-sdeA locus. Interestingly, while over-expression of SidE family proteins in a wild type Legionella strain has no effect, we found that their over-expression in a ∆sidJ mutant completely inhibits intracellular growth of the strain. In addition, we found expression of SidE proteins is toxic in both yeast and mammalian HEK293 cells, but this toxicity can be suppressed by co-expression of SidJ, suggesting that SidJ may modulate the function of SidE family proteins. Finally, we were able to demonstrate both in vivo and in vitro that SidJ acts on SidE proteins to mediate their disappearance from the LCV, thereby preventing lethal intoxication of host cells. Based on these findings, we propose that SidJ acts as a metaeffector to control the activity of other Legionella effectors.

Structure of the WipA protein reveals a novel tyrosine protein phosphatase effector from Legionella pneumophila.

PubMed

Pinotsis, Nikos; Waksman, Gabriel

2017-06-02

Legionnaires' disease is a severe form of pneumonia caused by the bacterium Legionella pneumophila. L. pneumophila pathogenicity relies on secretion of more than 300 effector proteins by a type IVb secretion system. Among these Legionella effectors, WipA has been primarily studied because of its dependence on a chaperone complex, IcmSW, for translocation through the secretion system, but its role in pathogenicity has remained unknown. In this study, we present the crystal structure of a large fragment of WipA, WipA435. Surprisingly, this structure revealed a serine/threonine phosphatase fold that unexpectedly targets tyrosine-phosphorylated peptides. The structure also revealed a sequence insertion that folds into an α-helical hairpin, the tip of which adopts a canonical coiled-coil structure. The purified protein was a dimer whose dimer interface involves interactions between the coiled coil of one WipA molecule and the phosphatase domain of another. Given the ubiquity of protein-protein interaction mediated by interactions between coiled-coils, we hypothesize that WipA can thereby transition from a homodimeric state to a heterodimeric state in which the coiled-coil region of WipA is engaged in a protein-protein interaction with a tyrosine-phosphorylated host target. In conclusion, these findings help advance our understanding of the molecular mechanisms of an effector involved in Legionella virulence and may inform approaches to elucidate the function of other effectors. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Unique Biofilm Signature, Drug Susceptibility and Decreased Virulence in Drosophila through the Pseudomonas aeruginosa Two-Component System PprAB

PubMed Central

Giraud, Caroline; Bernard, Christophe S.; Calderon, Virginie; Ewald, Friederike; Plésiat, Patrick; Nguyen, Cathy; Grunwald, Didier; Attree, Ina; Jeannot, Katy; Fauvarque, Marie-Odile

2012-01-01

Bacterial biofilm is considered as a particular lifestyle helping cells to survive hostile environments triggered by a variety of signals sensed and integrated through adequate regulatory pathways. Pseudomonas aeruginosa, a Gram-negative bacterium causing severe infections in humans, forms biofilms and is a fantastic example for fine-tuning of the transition between planktonic and community lifestyles through two-component systems (TCS). Here we decipher the regulon of the P. aeruginosa response regulator PprB of the TCS PprAB. We identified genes under the control of this TCS and once this pathway is activated, analyzed and dissected at the molecular level the PprB-dependent phenotypes in various models. The TCS PprAB triggers a hyper-biofilm phenotype with a unique adhesive signature made of BapA adhesin, a Type 1 secretion system (T1SS) substrate, CupE CU fimbriae, Flp Type IVb pili and eDNA without EPS involvement. This unique signature is associated with drug hyper-susceptibility, decreased virulence in acutely infected flies and cytotoxicity toward various cell types linked to decreased Type III secretion (T3SS). Moreover, once the PprB pathway is activated, decreased virulence in orally infected flies associated with enhanced biofilm formation and dissemination defect from the intestinal lumen toward the hemolymph compartment is reported. PprB may thus represent a key bacterial adaptation checkpoint of multicellular and aggregative behavior triggering the production of a unique matrix associated with peculiar antibiotic susceptibility and attenuated virulence, a particular interesting breach for therapeutic intervention to consider in view of possible eradication of P. aeruginosa biofilm-associated infections. PMID:23209420

Saturn Apollo Program

NASA Image and Video Library

1960-01-01

S-IVB-505 and S-IVB-211, the flight version of the S-IVB stages, in the McDornell Douglas' S-IVB Assembly and Checkout Tower in Huntington Beach, California. As a part of the Marshall Space Flight Center `s "building block" approach to the Saturn vehicle development, the S-IVB stage, in its 200 series, was utilized as the Saturn IB launch vehicle's second stage, and, in its 500 series, the Saturn V's third stage. The S-IVB was powered by a single J-2 engine, initially capable of 200,000 pounds of thrust.

Sequence and Role in Virulence of the Three Plasmid Complement of the Model Tumor-Inducing Bacterium Pseudomonas savastanoi pv. savastanoi NCPPB 3335

PubMed Central

Bardaji, Leire; Pérez-Martínez, Isabel; Rodríguez-Moreno, Luis; Rodríguez-Palenzuela, Pablo; Sundin, George W.; Ramos, Cayo; Murillo, Jesús

2011-01-01

Pseudomonas savastanoi pv. savastanoi NCPPB 3335 is a model for the study of the molecular basis of disease production and tumor formation in woody hosts, and its draft genome sequence has been recently obtained. Here we closed the sequence of the plasmid complement of this strain, composed of three circular molecules of 78,357 nt (pPsv48A), 45,220 nt (pPsv48B), and 42,103 nt (pPsv48C), all belonging to the pPT23A-like family of plasmids widely distributed in the P. syringae complex. A total of 152 coding sequences were predicted in the plasmid complement, of which 38 are hypothetical proteins and seven correspond to putative virulence genes. Plasmid pPsv48A contains an incomplete Type IVB secretion system, the type III secretion system (T3SS) effector gene hopAF1, gene ptz, involved in cytokinin biosynthesis, and three copies of a gene highly conserved in plant-associated proteobacteria, which is preceded by a hrp box motif. A complete Type IVA secretion system, a well conserved origin of transfer (oriT), and a homolog of the T3SS effector gene hopAO1 are present in pPsv48B, while pPsv48C contains a gene with significant homology to isopentenyl-diphosphate delta-isomerase, type 1. Several potential mobile elements were found on the three plasmids, including three types of MITE, a derivative of IS801, and a new transposon effector, ISPsy30. Although the replication regions of these three plasmids are phylogenetically closely related, their structure is diverse, suggesting that the plasmid architecture results from an active exchange of sequences. Artificial inoculations of olive plants with mutants cured of plasmids pPsv48A and pPsv48B showed that pPsv48A is necessary for full virulence and for the development of mature xylem vessels within the knots; we were unable to obtain mutants cured of pPsv48C, which contains five putative toxin-antitoxin genes. PMID:22022435

The solution structure of omega-Aga-IVB, a P-type calcium channel antagonist from venom of the funnel web spider, Agelenopsis aperta.

PubMed

Reily, M D; Thanabal, V; Adams, M E

1995-02-01

The 48 amino acid peptides omega-Aga-IVA and omega-Aga-IVB are the first agents known to specifically block P-type calcium channels in mammalian brain, thus complementing the existing suite of pharmacological tools used for characterizing calcium channels. These peptides provide a new set of probes for studies aimed at elucidating the structural basis underlying the subtype specificity of calcium channel antagonists. We used 288 NMR-derived constraints in a protocol combining distance geometry and molecular dynamics employing the program DGII, followed by energy minimization with Discover to derive the three-dimensional structure of omega-Aga-IVB. The toxin consists of a well-defined core region, comprising seven solvent-shielded residues and a well-defined triple-stranded beta-sheet. Four loop regions have average backbone rms deviations between 0.38 and 1.31 A, two of which are well-defined type-II beta-turns. Other structural features include disordered C- and N-termini and several conserved basic amino acids that are clustered on one face of the molecule. The reported structure suggests a possible surface for interaction with the channel. This surface contains amino acids that are identical to those of another known P-type calcium channel antagonist, omega-Aga-IVA, and is rich in basic residues that may have a role in binding to the anionic sites in the extracellular regions of the calcium channel.

Structural characterization of CFA/III and Longus type IVb pili from enterotoxigenic Escherichia coli.

PubMed

Kolappan, Subramaniapillai; Roos, Justin; Yuen, Alex S W; Pierce, Owen M; Craig, Lisa

2012-05-01

The type IV pili are helical filaments found on many Gram-negative pathogenic bacteria, with multiple diverse roles in pathogenesis, including microcolony formation, adhesion, and twitching motility. Many pathogenic enterotoxigenic Escherichia coli (ETEC) isolates express one of two type IV pili belonging to the type IVb subclass: CFA/III or Longus. Here we show a direct correlation between CFA/III expression and ETEC aggregation, suggesting that these pili, like the Vibrio cholerae toxin-coregulated pili (TCP), mediate microcolony formation. We report a 1.26-Å resolution crystal structure of CofA, the major pilin subunit from CFA/III. CofA is very similar in structure to V. cholerae TcpA but possesses a 10-amino-acid insertion that replaces part of the α2-helix with an irregular loop containing a 3(10)-helix. Homology modeling suggests a very similar structure for the Longus LngA pilin. A model for the CFA/III pilus filament was generated using the TCP electron microscopy reconstruction as a template. The unique 3(10)-helix insert fits perfectly within the gap between CofA globular domains. This insert, together with differences in surface-exposed residues, produces a filament that is smoother and more negatively charged than TCP. To explore the specificity of the type IV pilus assembly apparatus, CofA was expressed heterologously in V. cholerae by replacing the tcpA gene with that of cofA within the tcp operon. Although CofA was synthesized and processed by V. cholerae, no CFA/III filaments were detected, suggesting that the components of the type IVb pilus assembly system are highly specific to their pilin substrates.

45 CFR 1355.21 - E and IV-B.

Code of Federal Regulations, 2010 CFR

1996-10-01

... requirements for titles IV PUBLIC WELFARE Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN.... 1355.21 State plan requirements for titles IV-E and IV-B. (a) The State plans for titles IV-E and IV-B... contained in section 471(a)(8) of the Act. (b) The State plans for titles IV-E and IV-B must provide for...

Tachyphylaxis after intravitreal bevacizumab for exudative age-related macular degeneration.

PubMed

Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

2009-06-01

To describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD). We retrospectively reviewed the records of 59 consecutive patients treated with IVB at the National Eye Institute over a 14-month period and identified cases demonstrating loss of treatment efficacy as revealed by spectral domain optical coherence tomography. We defined tachyphylaxis as a loss of therapeutic response to IVB 28 +/- 7 days after administration in an eye that had previously demonstrated a therapeutic response in the same time interval. Five patients (six eyes) were identified as developing tachyphylaxis after repeated treatment with IVB. High-dose IVB (2.50 mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen after an episode of unilateral postinjection anterior uveitis. After the first treatment of IVB, the median time taken to develop tachyphylaxis was 100 weeks (range: 31-128 weeks), and the median number of IVB treatments to the development of tachyphylaxis was 8 treatments (range: 5-10 treatments). Tachyphylaxis can occur after long-term intravitreal use of bevacizumab in patients with AMD. The precise mechanism of tachyphylaxis is unclear, but both local and/or systemic factors may be involved.

Tachyphylaxis Following Intravitreal Bevacizumab for Exudative Age-Related Macular Degeneration

PubMed Central

Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.; Wong, Wai T.

2009-01-01

Purpose To describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD). Methods We retrospectively reviewed the records of 59 consecutive patients treated with IVB at the National Eye Institute over a 14 month period, and identified cases demonstrating loss of treatment efficacy as revealed by spectral domain optical coherence tomography. We defined tachyphylaxis as a loss of therapeutic response to IVB 28±7 days after administration in an eye which had previously demonstrated a therapeutic response in the same time interval. Results Five patients (6 eyes) were identified as developing tachyphylaxis following repeated treatment with IVB. High-dose IVB (2.50mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen following an episode of unilateral post-injection anterior uveitis. After the first treatment of IVB, the median time taken to develop tachyphylaxis was 100 weeks (range: 31-128 weeks), and the median number of IVB treatments to the development of tachyphylaxis was 8 treatments (range: 5-10). Conclusion Tachyphylaxis can occur following long-term intravitreal use of bevacizumab in patients with AMD. The precise mechanism of tachyphylaxis is unclear, but both local and/or systemic factors may be involved. PMID:19516114

Potential Reservoirs and Risk Factors for VHSV IVb in an Enzootic System: Budd Lake, Michigan.

PubMed

Throckmorton, Elizabeth; Brenden, Travis; Peters, Amber K; Newcomb, Tammy J; Whelan, Gary E; Faisal, Mohamed

2017-03-01

Viral hemorrhagic septicemia virus genotype IVb (VHSV IVb) has caused major, sporadic fish die-offs in the Laurentian Great Lakes region of North America since 2005. Presently, factors affecting VHSV IVb persistence in enzootic systems are not well understood. Even with annual surveillance, the virus can go undetected for several years after an outbreak before again re-emerging, which suggests that the virus is maintained in the system either below detectable levels or in untested reservoirs. The aim of this study was to identify potential reservoirs of VHSV IVb in Budd Lake, Michigan; VHSV IVb was first detected in Budd Lake in 2007 but remained undetected until 2011. Additionally, we explored the susceptibility of naive fish introduced into a water body enzootic for VHSV IVb by stocking age-0 Largemouth Bass Micropterus salmoides at varying densities into enclosures in the lake. The virus was not detected among samples of the fishes Notropis spp. and Lepomis spp., cylindrical papershell mussels Anodontoides ferussacianus, leeches (subclass Hirudinea), sediment, or water. However, the virus was successfully isolated from amphipods (family Hyalellidae) and Largemouth Bass held in the enclosures. Our finding of VHSV IVb in Hyalellidae amphipods in combination with other research that has detected the virus in Diporeia spp., a large benthic amphipod important as a food resource to Great Lake fishes, suggests that benthic macroinvertebrates are a reservoir for VHSV IVb in infected systems. If there are environmental reservoirs for VHSV IVb in infected systems, they are likely unevenly distributed. Findings of this study add to our understanding of the seemingly complex ecology of this deadly and economically detrimental virus. Received February 22, 2016; accepted October 16, 2016.

Cosmogenic effects on Cu isotopes in IVB iron meteorites

NASA Astrophysics Data System (ADS)

Chen, Heng; Moynier, Frédéric; Humayun, Munir; Bishop, M. Cole; Williams, Jeffrey T.

2016-06-01

We measured Cu isotope compositions of 12 out of the 14 known IVB iron meteorites. Our results show that IVB iron meteorites display a very large range of δ65Cu values (-5.84‰ < δ65Cu < -0.24‰; defined as per mil deviation of the 65Cu/63Cu ratio from the NIST-976 standard). These Cu isotopic data display clear correlations with W, Pt, and Os isotope ratios, which are very sensitive to secondary neutron capture due to galactic cosmic ray (GCR) irradiation. This demonstrates that δ65Cu in IVB irons is majorly modified by neutron capture by the reaction 62Ni(n,γ)63Ni followed by beta decay to 63Cu. Using correlations with Pt and Os neutron dosimeters, we calculated a pre-exposure δ65Cu of -0.3 ± 0.8‰ (95% conf.) of IVB irons that agrees well with the Cu isotopic compositions of other iron meteorite groups and falls within the range of chondrites. This shows that the volatile depletion of the IVB parent body is not due to evaporation that should have enriched IVB irons in the heavy Cu isotopes.

Overall view of Mission Operations Control in Mission Control Center

NASA Image and Video Library

1969-05-18

S69-34316 (18 May 1969) --- Overall view of the Mission Operations Control Room in the Mission Control Center, Building 30, on the first day of the Apollo 10 lunar orbit mission. A color television transmission was being received from Apollo 10. This picture was made following Command and Service Module/Lunar Module/Saturn IVB (CSM/LM-S-IVB) separation and prior to LM extraction from the S-IVB. The CSM were making the docking approach to the LM/S-IVB.

Inflight - Apollo X - MSC

NASA Image and Video Library

1969-05-18

S69-34039 (18 May 1969) --- Overall view of activity in the Mission Operations Control Room in the Mission Control Center, Building 30, on the first day of the Apollo 10 lunar orbit mission. This picture was taken following CSM/LM-S-IVB separation, and prior to LM extraction from the S-IVB. The telecast from the Apollo 10's color TV camera shows the LM still attached to the S-IVB. The CSM is making the docking approach to the LM/S-IVB.

Analysis of Several PLA2 mRNA in Human Meningiomas

PubMed Central

Denizot, Yves; De Armas, Rafael; Durand, Karine; Robert, Sandrine; Moreau, Jean-Jacques; Caire, François; Weinbreck, Nicolas; Labrousse, François

2009-01-01

In view of the important oncogenic action of phospholipase A2(PLA2) we investigated PLA2 transcripts in human meningiomas. Real-time PCR was used to investigate PLA2 transcripts in 26 human meningioma tumors. Results indicated that three Ca2+-dependent high molecular weight PLA2 (PLA2-IVA, PLA2-IVB, PLA2-IVC), one Ca2+-independent high molecular weight PLA2 (PLA2-VI) and five low molecular weight secreted forms of PLA2 (PLA2-IB, PLA2-IIA, PLA2-III, PLA2-V, and PLA2-XII) are expressed with PLA2-IVA, PLA2-IVB, PLA2-VI, and PLA2-XIIA as the major expressed forms. PLA2-IIE, PLA2-IIF, PLA2-IVD, and PLA2-XIIB are not detected. Plasma (PLA2-VIIA) and intracellular (PLA2-VIIB) platelet-activating factor acetylhydrolase transcripts are expressed in human meningiomas. However no difference was found for PLA2 transcript amounts in relation to the tumor grade, the subtype of meningiomas, the presence of inflammatory infiltrated cells, of an associated edema, mitosis, brain invasion, vascularisation or necrosis. In conclusion numerous genes encoding multiples forms of PLA2 are expressed in meningiomas where they might act on the phospholipid remodeling and on the local eicosanoid and/or cytokine networks. PMID:20339511

Functional genome analysis of Bifidobacterium breve UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor

PubMed Central

O'Connell Motherway, Mary; Zomer, Aldert; Leahy, Sinead C.; Reunanen, Justus; Bottacini, Francesca; Claesson, Marcus J.; O'Brien, Frances; Flynn, Kiera; Casey, Patrick G.; Moreno Munoz, Jose Antonio; Kearney, Breda; Houston, Aileen M.; O'Mahony, Caitlin; Higgins, Des G.; Shanahan, Fergus; Palva, Airi; de Vos, Willem M.; Fitzgerald, Gerald F.; Ventura, Marco; O'Toole, Paul W.; van Sinderen, Douwe

2011-01-01

Development of the human gut microbiota commences at birth, with bifidobacteria being among the first colonizers of the sterile newborn gastrointestinal tract. To date, the genetic basis of Bifidobacterium colonization and persistence remains poorly understood. Transcriptome analysis of the Bifidobacterium breve UCC2003 2.42-Mb genome in a murine colonization model revealed differential expression of a type IVb tight adherence (Tad) pilus-encoding gene cluster designated “tad2003.” Mutational analysis demonstrated that the tad2003 gene cluster is essential for efficient in vivo murine gut colonization, and immunogold transmission electron microscopy confirmed the presence of Tad pili at the poles of B. breve UCC2003 cells. Conservation of the Tad pilus-encoding locus among other B. breve strains and among sequenced Bifidobacterium genomes supports the notion of a ubiquitous pili-mediated host colonization and persistence mechanism for bifidobacteria. PMID:21690406

Functional genome analysis of Bifidobacterium breve UCC2003 reveals type IVb tight adherence (Tad) pili as an essential and conserved host-colonization factor.

PubMed

O'Connell Motherway, Mary; Zomer, Aldert; Leahy, Sinead C; Reunanen, Justus; Bottacini, Francesca; Claesson, Marcus J; O'Brien, Frances; Flynn, Kiera; Casey, Patrick G; Munoz, Jose Antonio Moreno; Kearney, Breda; Houston, Aileen M; O'Mahony, Caitlin; Higgins, Des G; Shanahan, Fergus; Palva, Airi; de Vos, Willem M; Fitzgerald, Gerald F; Ventura, Marco; O'Toole, Paul W; van Sinderen, Douwe

2011-07-05

Development of the human gut microbiota commences at birth, with bifidobacteria being among the first colonizers of the sterile newborn gastrointestinal tract. To date, the genetic basis of Bifidobacterium colonization and persistence remains poorly understood. Transcriptome analysis of the Bifidobacterium breve UCC2003 2.42-Mb genome in a murine colonization model revealed differential expression of a type IVb tight adherence (Tad) pilus-encoding gene cluster designated "tad(2003)." Mutational analysis demonstrated that the tad(2003) gene cluster is essential for efficient in vivo murine gut colonization, and immunogold transmission electron microscopy confirmed the presence of Tad pili at the poles of B. breve UCC2003 cells. Conservation of the Tad pilus-encoding locus among other B. breve strains and among sequenced Bifidobacterium genomes supports the notion of a ubiquitous pili-mediated host colonization and persistence mechanism for bifidobacteria.

Comparison of Intravitreal Bevacizumab, Intravitreal Ranibizumab and Laser Photocoagulation for Treatment of Type 1 Retinopathy of Prematurity in Turkish Preterm Children.

PubMed

Kabataş, Emrah Utku; Kurtul, Bengi Ece; Altıaylık Özer, Pınar; Kabataş, Naciye

2017-07-01

To evaluate effectiveness of treatment modalities, major complications and refractive errors in children who were treated with intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR) or laser photocoagulation (LP) for type 1 retinopathy of prematurity (ROP). Premature infants who underwent IVB monotherapy (Group 1), IVR monotherapy (Group 2) or LP (Group 3) for type 1 ROP and infants with spontaneously regressed ROP (Group 4) were included for the study. Major complications, recurrence rate, recurrence time, total retinal vascularization time and refractive errors at 18 months of corrected age (CA) were determined. Groups 1, 2, 3 and 4 included 24 eyes of 12 patients, 12 eyes of six patients, 72 eyes of 36 patients and 148 eyes of 74 patients, respectively. Recurrence of the disease occurred in two eyes of one patient in Group 1 at 52 weeks of postmenstrual age (PMA) and two eyes of one patient at 48 weeks of PMA in Group 2. In Group 3, disease did not regress after the first treatment in 10 eyes of five patients. The mean vascularization time in Group 1 was 73 ± 10.1 weeks of PMA and 61.8 ± 6.6 weeks of PMA in Group 2 (p = 0.027). Macular ectopia was seen in two eyes of one patient and exudative retinal detachment (ERD) occurred in two eyes of one patient in Group 3. Mean spherical equivalent was 1.49 ± 3.04 diopters (D) in Group 1, -1.79 ± 2.87D in Group 2, -1.27 ± 2.8 D in Group 3 and 1.52 ± 1.07 D in Group 4 at 18 months of CA. There was no significant difference in astigmatism values in all groups. IVB, IVR and LP are options that can successfully treat ROP. Myopia was observed to be the main refractive error in all treatment groups. Vascularization of the retina was completed later in the IVB group than in the IVR group.

Stenting for symptomatic intracranial vertebrobasilar artery stenosis: 30-day results in a high-volume stroke center.

PubMed

Liu, Lian; Zhao, Xiaojing; Mo, Dapeng; Ma, Ning; Gao, Feng; Miao, Zhongrong

2016-04-01

Symptomatic intracranial vertebrobasilar artery stenosis (IVBS) carries a high annual risk of recurrent stroke. Endovascular therapy was a promising technique but recent trials suggest it may carry a risk of periprocedual complications especially in inexperienced hands. This prospective study was to evaluate the safety of endovascular therapy for severe symptomatic IVBS in a high volume stroke centre. Patients with symptomatic IVBS caused by 70-99% stenosis despite medical treatment of at least one antiplatelet agent and statin were enrolled. The patients were treated either with balloon-mounted stent or balloon pre-dilation plus self-expanding stent as determined by the operators following a guideline. The primary outcome was 30-day stroke, transient ischemic attack (TIA) and death after stenting. The secondary outcome was successful stent deployment. The baseline characteristics and outcomes of patients with basilar artery (BA) lesions and patients with vertebral artery V4 segment lesions (BA group vs V4 group) were compared. And the outcome of different Mori type lesions was also compared. From September 2013 to September 2014, 105 patients with stroke or TIA due to intracranial IVBS were screened and 97 patients were treated by stenting, including 52 patients with BA stenosis and 45 patients with V4 stenosis. The rate of 30-day stroke, TIA and death was 7.1%. All the three strokes happened in the BA group and were perforator strokes. The successful stent deployment rate was 100%. General anesthesia was more preferred in the BA group than in the V4 groups (96.2% vs 75.6%, p=0.005). The Apollo stent was used more for Mori A lesions (30.5% vs 7.9%, p=0.011) and had lower degree of residual stenosis (8.6% vs 12.6%, p=0.014) than Wingspan stent. Mori C lesions were more likely to have higher degree of residual stenosis than Mori A lesion (15.3% vs 7.4%, p=0.005). The short-term safety of endovascular stenting for patients with severe symptomatic IVBS in a high volume stroke centre was acceptable. Mori A lesions may have lower residual stenosis rate than the Mori C type lesions. Copyright © 2016. Published by Elsevier B.V.

45 CFR 1357.30 - B).

Code of Federal Regulations, 2010 CFR

1996-10-01

... (title IV PUBLIC WELFARE Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT... TO TITLE IV-B Sec. 1357.30 Fiscal requirements (title IV-B). (a) The requirements of this section shall apply to all funds allotted or reallotted to States under title IV-B and to all funds not needed...

The Dot/Icm effector SdhA is necessary for virulence of Legionella pneumophila in Galleria mellonella and A/J mice.

PubMed

Harding, Clare R; Stoneham, Charlotte A; Schuelein, Ralf; Newton, Hayley; Oates, Clare V; Hartland, Elizabeth L; Schroeder, Gunnar N; Frankel, Gad

2013-07-01

Legionella pneumophila is an intracellular bacterium that resides within amoebae and macrophages in a specialized compartment termed the Legionella-containing vacuole (LCV). As well as providing an intracellular niche for replication, the LCV helps to prevent the release of bacterial components into the cytoplasm. Recognition of these components as danger signals by the host activates immune responses leading to clearance of the bacterium. Here, we examined the role of two important virulence factors of L. pneumophila, the potent danger signal flagellin and the translocated Dot/Icm type IVB secretion system effector SdhA, which is crucial to maintain LCV integrity, in the Galleria mellonella infection model. We demonstrate that flagellin expression does not contribute to virulence, replication, or induction of clearance mechanisms. Conversely, SdhA expression is important for virulence. We found that in the absence of SdhA, the LCV in hemocytes showed signs of instability and leakage. Furthermore, in contrast to wild-type L. pneumophila, a ΔsdhA mutant caused a transient depletion of hemocytes and reduced mortality. Analysis of the ΔsdhA mutant in the A/J mouse model also showed a significant replication defect. Together, our data underline the crucial importance of SdhA in infection across different model organisms.

The effect of intravitreal bevacizumab injection before Ahmed valve implantation in patients with neovascular glaucoma.

PubMed

Kang, Jung Youb; Nam, Ki Yup; Lee, Sang Joon; Lee, Seung Uk

2014-08-01

To evaluate the effect of intravitreal bevacizumab (IVB) before Ahmed valve implantation for treatment of neovascular glaucoma (NVG). This study is a retrospective, comparative, consecutive case series. The study group consisted of 27 eyes of 26 patients with NVG who underwent an Ahmed valve implantation. Thirteen eyes were treated with Ahmed valve implantation alone (control group), and 14 eyes were treated with a combination of preoperative IVB injection and Ahmed valve implantation (IVB group). Visual acuity, intraocular pressure (IOP), number of anti-glaucoma medications, surgical complications, and success rate were compared between the two groups. There were no significant differences in preoperative characteristics between the two groups. Visual acuity at 1, 2 weeks, and 1 month after surgery were significantly better in the IVB group (p = 0.038, 0.034, and 0.032, respectively). Hyphema associated with Ahmed valve implantation occurred significantly less in the IVB group (p = 0.016). On the other hand, the mean IOP and number of anti-glaucoma medications at all follow-up periods were similar between the two groups. Kaplan-Meier survival analysis showed the probability of success 6 months after surgery as 71.4 % in the IVB group and 84.6 % in the control group. No significant difference in success rate was found between the groups (p = 0.422). IVB before Ahmed valve implantation for treatment of NVG reduced the incidence of hyphema. In this retrospective study, IVB provided better visual outcome in the early postoperative periods but did not significantly improve mean IOP, number of anti-glaucoma medications, or success rate.

Saturn Apollo Program

NASA Image and Video Library

1967-01-01

This is a view of the Saturn V S-IVB (third) stage for the AS-209 (Apollo-Soyuz test project backup vehicle) on a transporter in the right foreground, and the S-IVB stage for AS-504 (Apollo 9 mission) being installed in the Beta Test Stand 1 at the SACTO facility in California. After the S-II (second) stage dropped away, the S-IVB (third) stage ignited and burned for about two minutes to place itself and the Apollo spacecraft into the desired Earth orbit. At the proper time during this Earth parking orbit, the S-IVB stage was re-ignited to speed the Apollo spacecraft to escape velocity and inject it and the astronauts into a moon trajectory. Developed and manufactured by the Douglas Aircraft Company in California, the S-IVB stage measures about 21.5 feet in diameter, about 58 feet in length, and is powered by a single 200,000-pound-thrust J-2 engine with a re-start capability. The S-IVB stage was also used on the second stage of the Saturn IB launch vehicle.

Gefitinib in Treating Patients With Metastatic or Unresectable Head and Neck Cancer or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-01-11

Anaplastic Thyroid Cancer; Insular Thyroid Cancer; Metastatic Parathyroid Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Parathyroid Cancer; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Thyroid Cancer; Recurrent Verrucous Carcinoma of the Larynx; Stage III Follicular Thyroid Cancer; Stage III Papillary Thyroid Cancer; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Larynx; Stage IIIB Non-small Cell Lung Cancer; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVA Basal Cell Carcinoma of the Lip; Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Follicular Thyroid Cancer; Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Lymphoepithelioma of the Oropharynx; Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVA Papillary Thyroid Cancer; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVB Basal Cell Carcinoma of the Lip; Stage IVB Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Follicular Thyroid Cancer; Stage IVB Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVB Lymphoepithelioma of the Oropharynx; Stage IVB Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVB Papillary Thyroid Cancer; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVC Basal Cell Carcinoma of the Lip; Stage IVC Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Follicular Thyroid Cancer; Stage IVC Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVC Lymphoepithelioma of the Oropharynx; Stage IVC Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVC Papillary Thyroid Cancer; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Thryoid Gland Nonmedullary Carcinoma; Thyroid Gland Medullary Carcinoma; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

Radiation Therapy With Durvalumab or Cetuximab in Treating Patients With Stage III-IVB Head and Neck Cancer Who Cannot Take Cisplatin

ClinicalTrials.gov

2018-06-15

Head and Neck Squamous Cell Carcinoma; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

Ipilimumab, Cetuximab, and Intensity-Modulated Radiation Therapy in Treating Patients With Previously Untreated Stage III-IVB Head and Neck Cancer

ClinicalTrials.gov

2018-05-23

Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

45 CFR 1357.40 - Direct payments to Indian Tribal Organizations (title IV-B, subpart 1, child welfare services).

Code of Federal Regulations, 2010 CFR

2010-10-01

... (title IV-B, subpart 1, child welfare services). 1357.40 Section 1357.40 Public Welfare Regulations... SERVICES THE ADMINISTRATION ON CHILDREN, YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION ASSISTANCE, AND CHILD AND FAMILY SERVICES REQUIREMENTS APPLICABLE TO TITLE IV-B § 1357.40 Direct payments to...

A Recombinant Viral Hemorrhagic Septicemia Virus Genotype IVb Glycoprotein Produced in Cabbage Looper Larvae Trichoplusia ni Elicits Antibody Response and Protection in Muskellunge.

PubMed

Standish, Isaac; Faisal, Mohamed

2017-06-01

The Novirhabdovirus viral hemorrhagic septicemia virus (VHSV) genotype IVb has caused serious fish kills and become endemic throughout the Great Lakes basin of North America. This is troublesome since there are no protective vaccines currently approved against this deadly disease even though recombinant technology has become increasingly common. Herein, we explored the production of a recombinant VHSV-IVb glycoprotein, believed to be important for virus infectivity, and determined its ability to elicit protection against challenge with the wild virus strain. A recombinant baculovirus containing a 5' 6x polyhistidine tag embedded in the VHSV-IVb G gene was used to infect the larvae of the cabbage looper Trichoplusia ni. A sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of affinity-purified protein yielded apparent VHSV-IVb glycoprotein at the expected molecular weight of ~65 kDa. The recombinant protein (rG) was used successfully in coating microtiter plate wells in an indirect enzyme-linked immunosorbent assay (ELISA), and positive anti-VHSV-IVb antibodies in Muskellunge Esox masquinongy were capable of binding to both the rG and purified whole VHSV-IVb, indicating epitope resemblance. In addition, the rG elicited a protective response in Muskellunge during a VHSV-IVb immersion challenge, resulting in 80% relative percent survival. Our results demonstrate that cabbage looper larvae can serve as an excellent production system for apparently conformationally correct viral glycoprotein. The incorporation of a polyhistidine tag facilitates obtaining highly purified protein in a relatively high concentration, which has potential in the development of an efficacious subunit vaccine against this deadly virus. Received September 11, 2016; accepted March 10, 2017.

Two-year visual results for older Asian women treated with photodynamic therapy or bevacizumab for myopic choroidal neovascularization.

PubMed

Ikuno, Yasushi; Nagai, Yoshimi; Matsuda, Satoshi; Arisawa, Akiko; Sho, Kenichiro; Oshita, Takashi; Takahashi, Kanji; Uchihori, Yasutaka; Gomi, Fumi

2010-01-01

To compare the long-term visual and anatomic outcome of treatment with photodynamic therapy (PDT) or intravitreal bevacizumab (IVB; Avastin; Genentech Inc, South San Francisco, California, USA) for choroidal neovascularization attributable to pathologic myopia (mCNV). An open-label, interventional case series. Multi-institutional. Thirty-one eyes of Japanese women who received either PDT or IVB for mCNV. Inclusion criteria were age 50 years or older, greatest linear dimension (GLD) 1200 to 3000 microm, and baseline best-corrected visual acuity (BCVA) 20/200 to 20/40. INTERVENTION PROCEDURES: Patients received either PDT or IVB (1 mg/40 microL) throughout the study, with re-treatment when necessary. BCVA and visual gain/loss at 3, 6, 12, 18, and 24 months after the initial treatment. Age, BCVA, location of CNV, refractive error, and symptom duration at baseline did not differ significantly between groups. BCVA was significantly improved at 3 to 12 months (P < .05); however, the significance was lost at 18 and 24 months in the IVB group. The PDT group showed no significant improvement within the first year, and vision slowly worsened after 12 months, becoming significantly worse at 18 and 24 months compared to baseline (P< .01). BCVA was significantly higher in the IVB group at 6 months (P< .05), and 12 months or further (P < .01). Visual gain was significantly greater in the IVB group at 6, 12, 18, and 24 months (P < .05 for 6, 18, and 24 months and P < .01 for 12 months). These findings indicate that the effects of PDT and IVB have a different time course, and that IVB provides a significantly better BCVA than PDT for mCNV over the long-term. Copyright 2010 Elsevier Inc. All rights reserved.

Saturn Apollo Program

NASA Image and Video Library

1968-01-01

This image depicts the Saturn V S-IVB (third) stage for the Apollo 10 mission being removed from the Beta Test Stand 1 after its acceptance test at the Douglas Aircraft Company's Sacramento Test Operations (SACTO) facility. After the S-II (second) stage dropped away, the S-IVB (third) stage was ignited and burned for about two minutes to place itself and the Apollo spacecraft into the desired Earth orbit. At the proper time during this Earth parking orbit, the S-IVB stage was re-ignited to speed the Apollo spacecraft to escape velocity injecting it and the astronauts into a moon trajectory. Developed and manufactured by the Douglas Aircraft Company in California, the S-IVB stage measures about 21.5 feet in diameter, about 58 feet in length, and powered by a single 200,000-pound-thrust J-2 engine with a re-start capability. The S-IVB stage was also used on the second stage of the Saturn IB launch vehicle.

Saturn Apollo Program

NASA Image and Video Library

1967-01-01

After the S-II (second) stage dropped away, the S-IVB (third) stage ignited and burned for about two minutes to place itself and the Apollo spacecraft into the desired Earth orbit. At the proper time during this Earth parking orbit, the S-IVB stage was re-ignited to speed the Apollo spacecraft to escape velocity, injecting it and the astronauts into a moon trajectory. Developed and manufactured by the Douglas Aircraft Company in Huntington, California, the S-IVB stage measures about 21.5 feet in diameter, about 58 feet in length and is powered by a single 200,000-pound-thrust J-2 engine with a re-start capability. The S-IVB stage was also used on the second stage of the Saturn IB launch vehicle. The fully-assembled S-IVB (third) stage for the AS-503 (Apollo 8 mission) launch vehicle is pictured in the Douglas' vertical checkout building.

Radiation Therapy With Cisplatin, Docetaxel, or Cetuximab After Surgery in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer

ClinicalTrials.gov

2017-05-18

Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Impact of previous cyst-enterostomy on patients’ outcome following resection of bile duct cysts

PubMed Central

Ouaissi, Mehdi; Kianmanesh, Reza; Ragot, Emilia; Belghiti, Jacques; Majno, Pietro; Nuzzo, Gennaro; Dubois, Remi; Revillon, Yann; Cherqui, Daniel; Azoulay, Daniel; Letoublon, Christian; Pruvot, François-René; Paye, François; Rat, Patrick; Boudjema, Karim; Roux, Adeline; Mabrut, Jean-Yves; Gigot, Jean-François

2016-01-01

AIM: To analyze the impact of previous cyst-enterostomy of patients underwent congenital bile duct cysts (BDC) resection. METHODS: A multicenter European retrospective study between 1974 and 2011 were conducted by the French Surgical Association. Only Todani subtypes I and IVb were included. Diagnostic imaging studies and operative and pathology reports underwent central revision. Patients with and without a previous history of cyst-enterostomy (CE) were compared. RESULTS: Among 243 patients with Todani types I and IVb BDC, 16 had undergone previous CE (6.5%). Patients with a prior history of CE experienced a greater incidence of preoperative cholangitis (75% vs 22.9%, P < 0.0001), had more complicated presentations (75% vs 40.5%, P = 0.007), and were more likely to have synchronous biliary cancer (31.3% vs 6.2%, P = 0.004) than patients without a prior CE. Overall morbidity (75% vs 33.5%; P < 0.0008), severe complications (43.8% vs 11.9%; P = 0.0026) and reoperation rates (37.5% vs 8.8%; P = 0.0032) were also significantly greater in patients with previous CE, and their Mayo Risk Score, during a median follow-up of 37.5 mo (range: 4-372 mo) indicated significantly more patients with fair and poor results (46.1% vs 15.6%; P = 0.0136). CONCLUSION: This is the large series to show that previous CE is associated with poorer short- and long-term results after Todani types I and IVb BDC resection. PMID:27358675

Ultra-low dose of intravitreal bevacizumab in retinopathy of prematurity.

PubMed

Şahin, A; Gürsel-Özkurt, Z; Şahin, M; Türkcü, F M; Yıldırım, A; Yüksel, H

2018-05-01

We aimed to investigate the effectivity of the 0.0625 mg dose of bevacizumab in patients with retinopathy of prematurity (ROP) and compare the results with 0.625 mg dose of intravitreal bevacizumab (IVB) injection. The medical records of the patients with type 1 ROP who received IVB monotherapy were retrospectively reviewed. Demographic and clinical characteristics of the patients were recorded. The patients were classified into two groups with respect to received dose of bevacizumab as follows: group F (n = 46) (full dose of bevacizumab-0.625 mg/0.025 ml) and group L (n = 45) (low dose (one tenth) of bevacizumab-0.0625 mg/0.025 ml). Both treatment dose regimens have similar outcomes. Moreover, the mean retinal vascularization time seemed to be significantly higher in group F compared to group L, 168 ± 65 and 97 ± 29 days, respectively (p < 0.001). Disappearance of plus sign is observed earlier in group F (2.45 ± 1.7 vs 3.66 ± 2.46 days, respectively, p = 0.03). The low dose (0.0625 mg) of IVB treatment was effective as full (0.625 mg) dose in ROP treatment. Moreover, our results showed that low-dose treatment might provide faster retinal vascularization than the regular used dose. On the other hand, disappearance of the plus sign takes longer time in patients treated with low dose compared to eyes treated with full dose of IVB that should be taken into account.

Apollo 7/S-IVB Rendezvous in space

NASA Technical Reports Server (NTRS)

1968-01-01

The expended Saturn IVB stage as photographed from the Apollo 7 spacecraft during transposition and docking maneuvers. This photograph was taken over Sonora, Mexico, during Apollo 7's second revolution of the Earth. The round, white disc inside the open panels of the Saturn IVB is a simulated docking target similar to that used on the lunar module for docking during lunar missions.

45 CFR 1356.70 - E to title IV-B.

Code of Federal Regulations, 2010 CFR

1996-10-01

... 45 PUBLIC WELFARE 4 1996-10-01 1996-10-01 false E to title IV-B. 1356.70 Sec. 1356.70 Transfer of funds from title IV PUBLIC WELFARE Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN... APPLICABLE TO TITLE IV-E Sec. 1356.70 Transfer of funds from title IV-E to title IV-B. (a)(1) Funds available...

Saturn Apollo Program

NASA Image and Video Library

1967-01-01

This cutaway illustration shows the Saturn V S-IVB (third) stage with the callouts of its major components. When the S-II (second) stage of the powerful Saturn V rocket burnt out and was separated the remaining units approached orbit around the Earth. Injection into the desired orbit was attaineded as the S-IVB (third stage) was ignited and burnt. The S-IVB stage was powered by a single 200,000-pound thrust J-2 engine and had a re-start capability built in for its J-2 engine. The S-IVB restarted to speed the Apollo spacecraft to escape velocity injecting it and the astronauts into a moon trajectory.

Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer

ClinicalTrials.gov

2018-01-12

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

Temsirolimus With or Without Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Cancer Who Did Not Respond to Previous Therapy

ClinicalTrials.gov

2017-02-23

Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma

Layered Compounds and Intercalation Chemistry: An Example of Chemistry and Diffusion in Solids.

ERIC Educational Resources Information Center

Whittingham, M. Stanley; Chianelli, Russell R.

1980-01-01

Considers a few areas of oxide/sulfide and intercalation-type chemistry. Discusses synthesis of the disulfides of the metals of group IVB, VB, and VIB; the intercalation reaction between lithium and titanium disulfide; other intercalates; and sulfide catalysts. (CS)

Apollo 7/S-IVB Rendezvous in space

NASA Image and Video Library

1968-10-11

AS07-03-1535 (11 Oct. 1968) --- The expended Saturn IVB stage as photographed from the Apollo 7 spacecraft during transposition and docking maneuvers at an altitude of 126 nautical miles, at ground elapsed time of three hours, 11 minutes. The round, white disc inside the open panels of the Saturn IVB is a simulated docking target similar to that used on the lunar module for docking during lunar missions. The spacecraft is directly over Odessa-Midland, Texas. The view between the two panels (area of large puffy clouds) extends southwest across Texas into the Mexican State of Chihuahua. The distance between the Apollo 7 spacecraft and the S-IVB is approximately 50 feet.

Effect of two different doses of intravitreal bevacizumab with temporal retina-sparing laser photocoagulation for retinopathy of prematurity.

PubMed

Choi, A Young; Cho, Hochan; Kim, Yu Cheol

2018-01-01

This study aims to compare the efficacy and safety between two different doses of intravitreal bevacizumab (IVB) injection with temporal retina-sparing laser (TRSL) photocoagulation for retinopathy of prematurity (ROP). We retrospectively evaluated 22 eyes of ROP infants who underwent IVB combined with partial TRSL for stage 3+ zone I or posterior zone II ROP. Laser photocoagulation was applied on the avascular retina, sparing two-disc-diameter width temporal avascular area anterior to ridge. A half dose (0.625 mg) or minimal dose (0.25 mg) of IVB was conducted. Four eyes in minimal dose group were retreated with IVB and laser photocoagulation on the spared retina. Of those 4 retreated eyes, three developed preretinal hemorrhage around the ridge after the first treatment, resulting in fibrotic macular dragging. A half dose of IVB may be more effective than a minimal dose with partial TRSL for ROP. Preretinal hemorrhage may be a harbinger of poor prognosis.

Apollo 7/S-IVB Rendezvous in space

NASA Image and Video Library

1968-10-11

AS07-03-1538 (11 Oct. 1968) --- The expended Saturn IVB stage as photographed from the Apollo 7 spacecraft during transposition and docking maneuvers. This photograph was taken during Apollo 7's second revolution of Earth. Earth below has heavy cloud cover. The round, white disc inside the open panels of the Saturn IVB is a simulated docking target similar to that used on the lunar module for docking during lunar missions.

Apollo 7/S-IVB Rendezvous in space

NASA Image and Video Library

1968-10-11

AS07-03-1531 (11 Oct. 1968) --- The expended Saturn IVB stage as photographed from the Apollo 7 spacecraft during transposition and docking maneuvers. This photograph was taken over Sonora, Mexico, during Apollo 7's second revolution of Earth. The round, white disc inside the open panels of the Saturn IVB is a simulated docking target similar to that used on the lunar module for docking during lunar missions.

Cisplatin With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

ClinicalTrials.gov

2017-03-22

Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma

Comparison of Bevacizumab, Ranibizumab, and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity in Turkey.

PubMed

Gunay, Murat; Sukgen, Emine Alyamac; Celik, Gokhan; Kocluk, Yusuf

2017-03-01

To evaluate the efficacies and treatment outcomes following intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR), and laser photocoagulation (LPC) in retinopathy of prematurity (ROP). This was a retrospective interventional case series study including the data of 134 infants (264 eyes) who were treated with IVB, IVR, or LPC for ROP. The data were collected from two major ROP treatment centers in Turkey without any randomization or masking. Regression of ROP, recurrence profile, complications after each treatment modality, and indications for retreatment were evaluated. The main outcome measures included the total inactivation of ROP with anatomic and refractive outcomes at 1.5 years of adjusted age. There were 55 infants (41.1%) in the IVB group, 22 infants (16.4%) in the IVR group, and 57 infants (42.5%) in the LPC group. All but 3 infants (5.5%) in the IVB group and 11 infants (50%) in the IVR group showed recurrence to stage 1 and 2 ROP following IVB and IVR (p < 0.001). Retreatment was performed in three infants in both IVB and IVR groups (p = 0.098). At 1.5 years of adjusted age, all infants showed favorable anatomic outcome except one infant in the LPC group. No significant difference of the mean spherical equivalent (SE) was observed between the groups (p = 0.131). In Zone I ROP, laser treated infants had significantly higher rates of myopia and high myopia than IVB and IVR treated infants (p = 0.040 and p = 0.019, respectively). Both IVB and IVR treated infants had significantly better refractive outcomes in Zone I ROP as compared to LPC treated infants at 1.5 years of adjusted age. The higher rate of disease recurrence was associated with IVR. Gestational age (GA) and the zone of ROP were also predictive factors for recurrence of ROP in the study.

5-FU Based Maintenance Therapy in RAS Wild Type Metastatic Colorectal Cancer After Induction With FOLFOX Plus Panitumumab

ClinicalTrials.gov

2018-03-28

Colorectal Adenocarcinoma; RAS Wild Type; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

Lenalidomide and Cetuximab in Treating Patients With Advanced Colorectal Cancer or Head and Neck Cancer

ClinicalTrials.gov

2018-05-23

Recurrent Colon Carcinoma; Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Rectal Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Verrucous Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Cancer AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Verrucous Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Cancer AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Rectal Cancer AJCC v7; Stage IVC Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Verrucous Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Oral Cavity Cancer AJCC v6 and v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

Phase II Randomized Trial of the Combination of Cetuximab and Sorafenib or Single Agent Cetuximab

ClinicalTrials.gov

2017-12-28

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

Sorafenib Tosylate, Cisplatin, and Docetaxel in Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

ClinicalTrials.gov

2018-05-22

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

PI3K Inhibitor BKM120 and Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

ClinicalTrials.gov

2017-05-22

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Onalespib in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin

ClinicalTrials.gov

2018-04-23

Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

CHOROIDAL THICKNESS CHANGES IN PROLIFERATIVE DIABETIC RETINOPATHY TREATED WITH PANRETINAL PHOTOCOAGULATION VERSUS PANRETINAL PHOTOCOAGULATION WITH INTRAVITREAL BEVACIZUMAB.

PubMed

Roohipoor, Ramak; Sharifian, Elaheh; Ghassemi, Fariba; Riazi-Esfahani, Mohammad; Karkhaneh, Reza; Fard, Masoud Aghsaei; Zarei, Mohammad; Modjtahedi, Bobeck S; Moghimi, Sasan

2016-10-01

To compare choroidal thickness (CT) and retinal thickness (RT) between eyes with proliferative diabetic retinopathy treated with panretinal photocoagulation (PRP) or PRP with intravitreal bevacizumab (PRP + IVB). Thirty-three patients with proliferative diabetic retinopathy were randomized to have one eye treated with PRP and the other with PRP + IVB. Change in CT was compared with baseline using enhanced depth imaging-optical coherence tomography at baseline and Months 1, 3, 6, and 10 after treatment. Change in RT was similarly assessed using spectral domain optical coherence tomography. Changes in both CT and RT were assessed in all nine macular areas as defined by Early Treatment Diabetic Retinopathy Study subfields. The PRP + IVB group had a significant decrease in subfoveal CT at 3 and 10 months (323.9 ± 62 μm at baseline vs. 320.7 ± 64.8 μm at Month 3 [P = 0.024] and 304.7 ± 65.6 μm at Month 10 [P = 0.003]). Subfoveal CT significantly decreased at 10 months compared with baseline in the PRP group (320.8 ± 57.7 at baseline to 297 ± 66.3 μm at 10 months, P = 0.01). Subfoveal CT was not significantly different between the 2 groups at 10 months. The best-corrected visual acuity did not change after treatment in the two groups, and there was no correlation between BCVA and CT changes (r = 0.222, P = 0.37 in the PRP group and r = 0.387, P = 0.12 in the PRP + IVB group). Significant increases in RT were seen in the PRP + IVB group at 6 months and in the PRP group at Months 1, 3, 6, and 10. A correlation between changes in CT and RT was only seen in the PRP group at 10 months after treatment. Eyes with proliferative diabetic retinopathy treated with PRP + IVB and PRP both had significant reduction in CT at 10 months; however, the eyes that were also treated with IVB also underwent an earlier but transient reduction at 3 months. Patients treated with IVB underwent less increase in RT.

Metallocene catalyst containing bulky organic group

DOEpatents

Marks, T.J.; Ja, L.; Yang, X.

1996-03-26

An ionic metallocene catalyst for olefin polymerization which comprises: (1) a cyclopentadienyl-type ligand, a Group IVB transition metal, and alkyl, aryl, or hydride substituents, as a cation, and (2) a weakly coordinating anion comprising boron substituted with halogenated, such as tetrafluoro-aryl substituents preferably containing silylalkyl substitution, such as para-silyl t-butyldimethyl.

Metallocene catalyst containing bulky organic group

DOEpatents

Marks, Tobin J.; Ja, Li; Yang, Xinmin

1996-03-26

An ionic metallocene catalyst for olefin polymerization which comprises: (1) a cyclopentadienyl-type ligand, a Group IVB transition metal, and alkyl, aryl, or hydride substituents, as a cation, and (2) a weakly coordinating anion comprising boron substituted with halogenated, such as tetra fluoro, aryl substituents preferably containing silylalkyl substitution, such as para-silyl t-butyldimethyl.

Conjugative type IVb pilus recognizes lipopolysaccharide of recipient cells to initiate PAPI-1 pathogenicity island transfer in Pseudomonas aeruginosa

USDA-ARS?s Scientific Manuscript database

Pseudomonas aeruginosa pathogenicity island 1 (PAPI-1) is one of the largest genomic islands of this important opportunistic human pathogen. Previous studies have shown that PAPI-1 encodes several putative virulence factors, a major regulator of biofilm formation, and antibiotic-resistance traits, a...

Structural Basis of Typhoid: Salmonella typhi Type IVb pilin (PilS) and Cystic Fibrosis Transmembrane Conductance Regulatory Interaction

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

Balakrishna, A.; Saxena, A; Mok, H

2009-01-01

The type IVb pilus of the enteropathogenic bacteria Salmonella typhi is a major adhesion factor during the entry of this pathogen into gastrointestinal epithelial cells. Its target of adhesion is a stretch of 10 residues from the first extracellular domain of cystic fibrosis transmembrane conductance regulator (CFTR). The crystal structure of the N-terminal 25 amino acid deleted S. typhi native PilS protein (PilS), which makes the pilus, was determined at 1.9 A resolution by the multiwavelength anomalous dispersion method. Also, the structure of the complex of PilS and a target CFTR peptide, determined at 1.8 A, confirms that residues 113-117more » (NKEER) of CFTR are involved in binding with the pilin protein and gives us insight on the amino acids that are essential for binding. Furthermore, we have also explored the role of a conserved disulfide bridge in pilus formation. The subunit structure and assembly architecture are crucial for understanding pilus functions and designing suitable therapeutics against typhoid.« less

Structural basis of typhod: Salmonella typhi type IVb pilin (PilS) and cystic fibrosis transmembrane conductance regulator interaction

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

Balakrishna, A.; Saxena, A; Mok, H

2009-01-01

The type IVb pilus of the enteropathogenic bacteria Salmonella typhi is a major adhesion factor during the entry of this pathogen into gastrointestinal epithelial cells. Its target of adhesion is a stretch of 10 residues from the first extracellular domain of cystic fibrosis transmembrane conductance regulator (CFTR). The crystal structure of the N-terminal 25 amino acid deleted S. typhi native PilS protein (PilS), which makes the pilus, was determined at 1.9 A resolution by the multiwavelength anomalous dispersion method. Also, the structure of the complex of PilS and a target CFTR peptide, determined at 1.8 A, confirms that residues 113-117more » (NKEER) of CFTR are involved in binding with the pilin protein and gives us insight on the amino acids that are essential for binding. Furthermore, we have also explored the role of a conserved disulfide bridge in pilus formation. The subunit structure and assembly architecture are crucial for understanding pilus functions and designing suitable therapeutics against typhoid.« less

Cisplatin, Intensity-Modulated Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-05-18

CDKN2A-p16 Negative; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

PubMed Central

Arevalo, J. Fernando; Sanchez, Juan G.; Lasave, Andres F.; Wu, Lihteh; Maia, Mauricio; Bonafonte, Sergio; Brito, Miguel; Alezzandrini, Arturo A.; Restrepo, Natalia; Berrocal, Maria H.; Saravia, Mario; Farah, Michel Eid; Fromow-Guerra, Jans; Morales-Canton, Virgilio

2011-01-01

This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy. PMID:21584260

Cetuximab and Radiation Therapy in Treating Patients With Stage III-IV Head and Neck Cancer

ClinicalTrials.gov

2017-11-15

Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Tongue Cancer

Intravitreal bevacizumab and dexamethasone implant for treatment of chronic diabetic macular edema.

PubMed

Güler, Emre; Totan, Yüksel; Betül Güragaç, Fatma

2017-06-01

To evaluate anatomical and functional outcomes of intraviteal bevacizumab (IVB) in patients with chronic diabetic macular edema (DME), and the effectivity and safety of dexamethasone implant in those unresponsive to regular IVB treatment. Thirty-five eyes of 35 patients (16 male and 19 female) with chronic DME (central foveal thickness (CFT)  > 275 μm, duration  > 6 months) received three injections of 2.5 mg IVB with six-week intervals. At 18 weeks, dexamethasone implant was applied to patients unresponsive to IVB. Main outcomes were the change in best corrected visual acuity (BCVA), CFT and ocular and systemic adverse effects for both drugs. The patients responsive to IVB were followed up for 36 weeks and those patients receiving dexamethasone implant were followed up for 24 weeks postoperatively. At 18 weeks, the mean BCVA (0.68 ± 0.40 logMAR, p = 0.45) and CFT (453 ± 169 μm, p = 0.58) did not show any significant change compared to baseline (0.74 ± 0.42 logMAR and 521 ± 151 μm, respectively). In 20 patients (%57.1) responsive to IVB, the CFT was significantly improved from 12 to 36 weeks with the mean value of 295 ± 42 μ (p = 0.01). However, no significant difference was observed for BCVA during this period (p = 0.17). Dexamethasone was implanted in 15 eyes (42.8%) unresponsive to IVB at 18 weeks. Statistically significant improvements were observed in BCVA (at postoperative 4 and 12 weeks) and CFT (at postoperative 4, 12 and 24 weeks). In addition, both parameters significantly worsened at 24 weeks compared to 12 weeks (p < 0.001 and p = 0.01, respectively). Patients with chronic DME should be followed in accordance with a fixed treatment protocol combining anti-VEGF and steroid treatments.

Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-06-19

Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Major Salivary Gland Cancer AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Verrucous Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Cancer AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Verrucous Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Cancer AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Verrucous Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Oral Cavity Cancer AJCC v6 and v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

21 CFR 178.3780 - Polyhydric alcohol esters of long chain monobasic acids.

Code of Federal Regulations, 2014 CFR

2014-04-01

... § 177.1980 of this chapter that contact food of Types I, II, IV-B, VI-B, VII-B, and VIII identified in... produced by the reaction of either ethylene glycol or glycerol with long chain monobasic acids containing... carboxylic acids in the formation of the glycerol esters being neutralized with calcium hydroxide to produce...

Pathogen effector protein screening in yeast identifies Legionella factors that interfere with membrane trafficking.

PubMed

Shohdy, Nadim; Efe, Jem A; Emr, Scott D; Shuman, Howard A

2005-03-29

Legionella pneumophila invades and replicates intracellularly in human and protozoan hosts. The bacteria use the Icm/Dot type IVB secretion system to translocate effectors that inhibit phagosome maturation and modulate host vesicle trafficking pathways. To understand how L. pneumophila modulates organelle trafficking in host cells, we carried out pathogen effector protein screening in yeast, identifying L. pneumophila genes that produced membrane trafficking [vacuole protein sorting (VPS)] defects in yeast. We identified four L. pneumophila DNA fragments that perturb sorting of vacuolar proteins. Three encode ORFs of unknown function that are translocated via the Icm/Dot transporter from Legionella into macrophages. VPS inhibitor protein (Vip) A is a coiled-coil protein, VipD is a patatin domain-containing protein, and VipF contains an acetyltransferase domain. Processing studies in yeast indicate that VipA, VipD, and VipF inhibit lysosomal protein trafficking by different mechanisms; overexpressing VipA has an effect on carboxypeptidase Y trafficking, whereas VipD interferes with multivesicular body formation at the late endosome and endoplasmic reticulum-to-Golgi body transport. Such differences highlight the multiple strategies L. pneumophila effectors use to subvert host trafficking processes. Using yeast as an effector gene discovery tool allows for a powerful, genetic approach to both the identification of virulence factors and the study of their function.

Lunar Module 3 attached to Saturn V third stage

NASA Image and Video Library

1969-03-03

AS09-19-2919 (3 March 1969) --- The Lunar Module (LM) "Spider", still attached to the Saturn V third (S-IVB) stage, is photographed from the Command and Service Modules (CSM) "Gumdrop" on the first day of the Apollo 9 Earth-orbital mission. This picture was taken following CSM/LM-S-IVB separation and prior to LM extraction from the S-IVB. The Spacecraft Lunar Module Adapter (SLA) panels have already been jettisoned. Inside the Command Module were astronauts James A. McDivitt, commander; David R. Scott, command module pilot; and Russell L. Schweickart, lunar module pilot.

Phase I Study of Cetuximab With RO4929097 in Metastatic Colorectal Cancer

ClinicalTrials.gov

2015-05-15

Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131

ClinicalTrials.gov

2014-08-20

Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

Efficacy and safety of intravitreal bevacizumab in eyes with neovascular glaucoma undergoing Ahmed glaucoma valve implantation: 2-year follow-up.

PubMed

Arcieri, Enyr S; Paula, Jayter S; Jorge, Rodrigo; Barella, Kleyton A; Arcieri, Rafael S; Secches, Danilo J; Costa, Vital P

2015-02-01

To evaluate the efficacy and safety of intravitreal bevacizumab (IVB) in eyes with neovascular glaucoma (NVG) undergoing Ahmed glaucoma valve (AGV) implantation. This was a multicentre, prospective, randomized clinical trial that enrolled 40 patients with uncontrolled neovascular glaucoma that had undergone panretinal photocoagulation and required glaucoma drainage device implantation. Patients were randomized to receive IVB (1.25 mg) or not during Ahmed valve implant surgery. Injections were administered intra-operatively, and 4 and 8 weeks after surgery. After a mean follow-up of 2.25 ± 0.67 years (range 1.5-3 years), both groups showed a significant decrease in IOP (p < 0.05). There was no difference in IOP between groups except at the 18-month interval, when IOP in IVB group was significantly lower (14.57 ± 1.72 mmHg vs. 18.37 ± 1.06 mmHg - p = 0.0002). There was no difference in survival success rates between groups. At 24 months, there was a trend to patients treated with IVB using less antiglaucoma medications than the control group (p = 0.0648). Complete regression of rubeosis iridis was significantly more frequent in the IVB group (80%) than in the control group (25%) (p = 0.0015). Intravitreal bevacizumab may lead to regression of new vessels both in the iris and in the anterior chamber angle in patients with neovascular glaucoma undergoing Ahmed glaucoma valve implantation. There is a trend to slightly lower IOPs and number of medications with IVB use during AGV implantation for neovascular glaucoma. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Regression Rates Following the Treatment of Aggressive Posterior Retinopathy of Prematurity with Bevacizumab Versus Laser: 8-Year Retrospective Analysis

PubMed Central

Nicoară, Simona D.; Ştefănuţ, Anne C.; Nascutzy, Constanta; Zaharie, Gabriela C.; Toader, Laura E.; Drugan, Tudor C.

2016-01-01

Background Retinopathy is a serious complication related to prematurity and a leading cause of childhood blindness. The aggressive posterior form of retinopathy of prematurity (APROP) has a worse anatomical and functional outcome following laser therapy, as compared with the classic form of the disease. The main outcome measures are the APROP regression rate, structural outcomes, and complications associated with intravitreal bevacizumab (IVB) versus laser photocoagulation in APROP. Material/Methods This is a retrospective case series that includes infants with APROP who received either IVB or laser photocoagulation and had a follow-up of at least 60 weeks (for the laser photocoagulation group) and 80 weeks (for the IVB group). In the first group, laser photocoagulation of the retina was carried out and in the second group, 1 bevacizumab injection was administered intravitreally. The following parameters were analyzed in each group: sex, gestational age, birth weight, postnatal age and postmenstrual age at treatment, APROP regression, sequelae, and complications. Statistical analysis was performed using Microsoft Excel and IBM SPSS (version 23.0). Results The laser photocoagulation group consisted of 6 premature infants (12 eyes) and the IVB group consisted of 17 premature infants (34 eyes). Within the laser photocoagulation group, the evolution was favorable in 9 eyes (75%) and unfavorable in 3 eyes (25%). Within the IVB group, APROP regressed in 29 eyes (85.29%) and failed to regress in 5 eyes (14.71%). These differences are statistically significant, as proved by the McNemar test (P<0.001). Conclusions The IVB group had a statistically significant better outcome compared with the laser photocoagulation group, in APROP in our series. PMID:27062023

21 CFR 178.3295 - Clarifying agents for polymers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Clarifying agents for polymers. 178.3295 Section... Production Aids § 178.3295 Clarifying agents for polymers. Clarifying agents may be safely used in polymers... polymers contact food only of types I, II, IV-B, VI-B, VII-B, and VIII as identified in Table 1 of § 176...

SU-F-T-23: Correspondence Factor Correction Coefficient for Commissioning of Leipzig and Valencia Applicators with the Standard Imaging IVB 1000

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

Donaghue, J; Gajdos, S

Purpose: To determine the correction factor of the correspondence factor for the Standard Imaging IVB 1000 well chamber for commissioning of Elekta’s Leipzig and Valencia skin applicators. Methods: The Leipzig and Valencia applicators are designed to treat small skin lesions by collimating irradiation to the treatment area. Published output factors are used to calculate dose rates for clinical treatments. To validate onsite applicators, a correspondence factor (CFrev) is measured and compared to published values. The published CFrev is based on well chamber model SI HDR 1000 Plus. The CFrev is determined by correlating raw values of the source calibration setupmore » (Rcal,raw) and values taken when each applicator is mounted on the same well chamber with an adapter (Rapp,raw). The CFrev is calculated by using the equation CFrev =Rapp,raw/Rcal,raw. The CFrev was measured for each applicator in both the SI HDR 1000 Plus and the SI IVB 1000. A correction factor, CFIVB for the SI IVB 1000 was determined by finding the ratio of CFrev (SI IVB 1000) and CFrev (SI HDR 1000 Plus). Results: The average correction factors at dwell position 1121 were found to be 1.073, 1.039, 1.209, 1.091, and 1.058 for the Valencia V2, Valencia V3, Leipzig H1, Leipzig H2, and Leipzig H3 respectively. There were no significant variations in the correction factor for dwell positions 1119 through 1121. Conclusion: By using the appropriate correction factor, the correspondence factors for the Leipzig and Valencia surface applicators can be validated with the Standard Imaging IVB 1000. This allows users to correlate their measurements with the Standard Imaging IVB 1000 to the published data. The correction factor is included in the equation for the CFrev as follows: CFrev= Rapp,raw/(CFIVB*Rcal,raw). Each individual applicator has its own correction factor, so care must be taken that the appropriate factor is used.« less

Seismic reading taken at MSC recording impact of Apollo 13 S-IVB with surface

NASA Technical Reports Server (NTRS)

1970-01-01

A seismic reading taken from instruments at the Manned Spacecraft Center (MSC) recording impact of the Apollo 13 S-IVB/Instrument Unit with lunar surface. The expended Saturn third stage and instrument unit impacted the lunar surface at 7:09 p.m., April 14, 1970. The location of the impact was 2.4 degrees south latitude and 27.9 degrees west longitude, about 76 nautical miles west-northwest of the Apollo 12 Lunar Surface Experiment package deployment site. The S-IVB/IU impact was picked up by the Passive Seismic Experiment, a component of the package and transmitted to instruments at the Mission Control Center.

Apollo 7/S-IVB Rendezvous in space

NASA Technical Reports Server (NTRS)

1968-01-01

The expended Saturn IVB stage as photographed from the Apollo 7 spacecraft during transposition and docking maneuvers at an altitude of 126 nautical miles, at ground elapsed time of three hours, 11 minutes. The round, white disc inside the open panels of the Saturn IVB is a simulated docking target similar to that used on the lunar module for docking during lunar missions. The spacecraft is directly over Odessa-Midland, Texas. The view between the two panels (area of large puffy clouds) extends southwest across Texas into the Mexican State of Chihuahua. The distance between the Apollo 7 spacecraft and the S-(VB is approximately 50 feet.

Sunitinib in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery

ClinicalTrials.gov

2017-08-18

Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Medullary Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma

GTI-2040, Oxaliplatin, and Capecitabine in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer or Other Solid Tumors

ClinicalTrials.gov

2013-03-26

Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Dose Escalation Versus Standard in Laryngopharyngeal Cancers

ClinicalTrials.gov

2018-04-12

Malignant Neoplasm of Oropharynx Stage III; Malignant Neoplasm of Larynx Stage III; Malignant Neoplasm of Hypopharynx Stage III; Malignant Neoplasm of Oropharynx Stage IVa; Malignant Neoplasm of Oropharynx Stage IVb; Malignant Neoplasm of Larynx Stage IV; Malignant Neoplasm of Hypopharynx Stage IVa; Malignant Neoplasm of Hypopharynx Stage IVb

Replication and persistence of VHSV IVb in freshwater turtles.

PubMed

Goodwin, Andrew E; Merry, Gwenn E

2011-05-09

With the emergence of viral hemorrhagic septicemia virus (VHSV) strain IVb in the Great Lakes of North America, hatchery managers have become concerned that this important pathogen could be transmitted by animals other than fish. Turtles are likely candidates because they are poikilotherms that feed on dead fish, but there are very few reports of rhabdovirus infections in reptiles and no reports of the fish rhabdoviruses in animals other than teleosts. We injected common snapping turtles Chelydra serpentine and red-eared sliders Trachemys scripta elegans intraperitoneally with 10(4) median tissue culture infectious dose (TCID50) of VHSV-IVb and 21 d later were able to detect the virus by quantitative real-time reverse transcriptase PCR (qrt-RTPCR) in pools of kidney, liver, and spleen. In a second experiment, snapping turtles, red-eared sliders, yellow-bellied sliders T. scripta scripta, and northern map turtles Grapetemys geographica at 14 degrees C were allowed to feed on tissues from bluegill dying of VHSV IVb disease. Turtle kidney, spleen, and brain pools were not positive by qrt-RTPCR on Day 3 post feeding, but were positive on Days 10 and 20. Map turtles on Day 20 post-feeding were positive by both qrt-RTPCR and by cell culture. Our work shows that turtles that consume infected fish are a possible vector for VHSV IVb, and that the fish rhabdoviruses may have a broader host range than previously suspected.

Erlotinib, Docetaxel, and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

ClinicalTrials.gov

2014-06-05

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

Self-Advocacy Serious Game in Advanced Cancer

ClinicalTrials.gov

2018-04-05

Ovarian Cancer Stage III; Ovarian Cancer Stage IV; Breast Cancer Stage IV; Cervical Cancer Stage IIIB; Cervical Cancer Stage IVA; Cervical Cancer Stage IVB; Endometrial Cancer Stage III; Endometrial Cancer Stage IV; Vulvar Cancer, Stage III; Vulvar Cancer, Stage IV; Vaginal Cancer Stage III; Vaginal Cancer Stage IVA; Vaginal Cancer Stage IVB

Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate in Advanced Colorectal Cancer

ClinicalTrials.gov

2013-01-31

Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Brentuximab Vedotin and Combination Chemotherapy in Treating Children and Young Adults With Stage IIB or Stage IIIB-IVB Hodgkin Lymphoma

ClinicalTrials.gov

2018-06-25

Ann Arbor Stage IIB Hodgkin Lymphoma; Ann Arbor Stage IIIB Hodgkin Lymphoma; Ann Arbor Stage IV Hodgkin Lymphoma; Ann Arbor Stage IVA Hodgkin Lymphoma; Ann Arbor Stage IVB Hodgkin Lymphoma; Childhood Hodgkin Lymphoma; Classic Hodgkin Lymphoma

45 CFR 1357.40 - B, subpart 1, child welfare services).

Code of Federal Regulations, 2010 CFR

1996-10-01

.... 1357.40 Direct payments to Indian Tribal Organizations (title IV PUBLIC WELFARE Regulations Relating to... FOR CHILDREN, YOUTH AND FAMILIES, REQUIREMENTS APPLICABLE TO TITLE IV-B Sec. 1357.40 Direct payments to Indian Tribal Organizations (title IV-B, subpart 1, child welfare services). (a) Who may apply for...

20 CFR 638.100 - General.

Code of Federal Regulations, 2010 CFR

2010-04-01

...' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Purpose and Scope § 638.100 General. (a) Purpose and scope. The... Job Corps program, authorized under title IV-B of the Job Training Partnership Act (Act). Job Corps is...

Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

ClinicalTrials.gov

2018-05-08

Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma AJCC v7; Stage III Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVA Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVB Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVC Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVC Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Thyroglobulin Antibody Negative; Thyroid Gland Undifferentiated (Anaplastic) Carcinoma

Saturn Apollo Program

NASA Image and Video Library

1967-01-01

Workers at McDornel-Douglas install the Saturn IB S-IVB (second) stage for the Apollo-Soyuz mission into the company's S-IVB assembly and checkout tower in Huntington Beach, California. The Saturn IB launch vehicle was developed by the Marshall Space Flight Center (MSFC) as an interim vehicle in its "building block" approach to Saturn rocket development. This vehicle utilized the Saturn I technology to further develop and refine the capabilities of a larger booster and the Apollo spacecraft required for the manned lunar missions. The S-IVB stage, later used as the third stage of the Saturn V launch vehicle, was powered by a single J-2 engine initially capable of 200,000 pounds of thrust.

Iodine I 131 and Pazopanib Hydrochloride in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer Previously Treated With Iodine I 131 That Cannot Be Removed By Surgery

ClinicalTrials.gov

2015-11-04

Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

Triapine, Cisplatin, and Radiation Therapy in Treating Patients With Cervical Cancer or Vaginal Cancer

ClinicalTrials.gov

2017-10-16

Recurrent Cervical Cancer; Recurrent Vaginal Cancer; Stage IB Cervical Cancer; Stage II Vaginal Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Vaginal Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer; Therapy-related Toxicity

45 CFR 1357.30 - State fiscal requirements (title IV-B, subpart 1, child welfare services).

Code of Federal Regulations, 2013 CFR

2013-10-01

... match the title IV-B, subpart 1 allotment may include foster care maintenance expenditures in any amount... (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON CHILDREN, YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION ASSISTANCE, AND CHILD AND...

45 CFR 1357.30 - State fiscal requirements (title IV-B, subpart 1, child welfare services).

Code of Federal Regulations, 2012 CFR

2012-10-01

... match the title IV-B, subpart 1 allotment may include foster care maintenance expenditures in any amount... (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON CHILDREN, YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION ASSISTANCE, AND CHILD AND...

45 CFR 1357.30 - State fiscal requirements (title IV-B, subpart 1, child welfare services).

Code of Federal Regulations, 2010 CFR

2010-10-01

... match the title IV-B, subpart 1 allotment may include foster care maintenance expenditures in any amount... (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON CHILDREN, YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION ASSISTANCE, AND CHILD AND...

45 CFR 1357.30 - State fiscal requirements (title IV-B, subpart 1, child welfare services).

Code of Federal Regulations, 2011 CFR

2011-10-01

... match the title IV-B, subpart 1 allotment may include foster care maintenance expenditures in any amount... (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON CHILDREN, YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION ASSISTANCE, AND CHILD AND...

Cediranib Maleate and Whole Brain Radiation Therapy in Patients With Brain Metastases From Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-03-07

Male Breast Cancer; Stage IV Breast Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Tumors Metastatic to Brain

45 CFR 1357.32 - State fiscal requirements (title IV-B, subpart 2, family preservation and family support services).

Code of Federal Regulations, 2010 CFR

2010-10-01

... following: Procurement; payroll; personnel functions; management, maintenance and operation of space and... SERVICES THE ADMINISTRATION ON CHILDREN, YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION... title IV-B may not be used for the purchase or construction of facilities. (f) Maintenance of effort...

Ziv-Aflibercept Followed by Ziv-Aflibercept, Fluorouracil, and Leucovorin Calcium in Treating Patients With Stage IV Colorectal Cancer

ClinicalTrials.gov

2015-05-04

Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Third Stage (S-IVB) At KSC

NASA Technical Reports Server (NTRS)

1960-01-01

A NASA technician is dwarfed by the gigantic Third Stage (S-IVB) as it rests on supports in a facility at KSC. The towering 363-foot Saturn V was a multi-stage, multi-engine launch vehicle standing taller than the Statue of Liberty. Altogether, the Saturn V engines produced as much power as 85 Hoover Dams.

Expression kinetics of key genes in the early innate immune response to Great Lakes viral hemorrhagic septicemia virus IVb infection in yellow perch (Perca flavescens)

USGS Publications Warehouse

Olson, Wendy; Emmenegger, Eveline; Glenn, Jolene; Simchick, Crystal; Winton, Jim; Goetz, Frederick

2013-01-01

The recently discovered strain of viral hemorrhagic septicemia virus, VHSV-IVb, represents an example of the introduction of an extremely pathogenic rhabdovirus capable of infecting a wide variety of new fish species in a new host-environment. The goal of the present study was to delineate the expression kinetics of key genes in the innate immune response relative to the very early stages of VHSV-IVb infection using the yellow perch (Perca flavescens) as a model. Administration of VHSV-IVb by IP-injection into juvenile yellow perch resulted in 84% cumulative mortality, indicating their high susceptibility to this disease. In fish sampled in the very early stages of infection, a significant up-regulation of Mx gene expression in the liver, as well as IL-1β and SAA activation in the head kidney, spleen, and liver was directly correlated to viral load. The potential down-regulation of Mx in the hematopoietic tissues, head kidney and spleen, may represent a strategy utilized by the virus to increase replication.

LRO Finds Apollo 16 Booster Rocket Impact Site

NASA Image and Video Library

2017-12-08

After decades of uncertainty, the Apollo 16 S-IVB impact site on the lunar surface has been identified. S-IVBs were portions of the Saturn V rockets that brought astronauts to the moon. The site was identified in imagery from the high-resolution LROC Narrow Angle Camera aboard NASA's Lunar Reconnaissance Orbiter. Beginning with Apollo 13, the S-IVB rocket stages were deliberately impacted on the lunar surface after they were used. Seismometers placed on the moon by earlier Apollo astronauts measured the energy of these impacts to shed light on the internal lunar structure. Locations of the craters that the boosters left behind were estimated from tracking data collected just prior to the impacts. Earlier in the LRO mission, the Apollo 13, 14, 15 and 17 impact sites were successfully identified, but Apollo 16's remained elusive. In the case of Apollo 16, radio contact with the booster was lost before the impact, so the location was only poorly known. Positive identification of the Apollo 16 S-IVB site took more time than the other four impact craters because the location ended up differing by about 30 km (about 19 miles) from the Apollo-era tracking estimate. (For comparison, the other four S-IVB craters were all within 7 km -- about four miles -- of their estimated locations.) Apollo 16's S-IVB stage is on Mare Insularum, about 160 miles southwest of Copernicus Crater (more precisely: 1.921 degrees north, 335.377 degrees east, minus 1,104 meters elevation). Credit: NASA/Goddard/Arizona State University NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Viral hemorrhagic septicemia IVb status in the United States: inferences from surveillance activities and regional context.

PubMed

Gustafson, L L; Remmenga, M D; Gardner, I A; Hartman, K H; Creekmore, L H; Goodwin, A E; Whaley, J E; Warg, J V; Gardner, S L; Scott, A E

2014-06-01

The United States (U.S.) response to viral hemorrhagic septicemia virus (VHSV) IVb emergence in the Laurentian Great Lakes (GL) included risk-based surveillance for cost-effective decision support regarding the health of fish populations in open systems. All U.S. VHSV IVb isolations to date derive from free-ranging fish from GL States. Most originate in the region designated by US Geological Survey hydrologic unit code (HUC) 04, with the exception of two detections in neighboring Upper Mississippi (HUC 05) and Ohio (HUC 07) regions. For States outside the GL system, disease probability was assessed using multiple evidence sources. None substantiated VHSV IVb absence using surveillance alone, in part due to the limited temporal relevance of data in open systems. However, Bayesian odds risk-based analysis of surveillance and population context, coupled with exclusions where water temperatures likely preclude viral replication, achieved VHSV IVb freedom assurance for 14 non-GL States by the end of 2012, with partial evidence obtained for another 17 States. The non-GL region (defined as the aggregate of 4-digit HUCs located outside of GL States) met disease freedom targets for 2012 and is projected to maintain this status through 2016 without additional active surveillance. Projections hinge on continued basic biosecurity conditions such as movement restrictions and passive surveillance. Areas with navigable waterway connections to VHSV IVb-affected HUCs (and conducive water temperatures) should receive priority for resources in future surveillance or capacity building efforts. However, 6 years of absence of detections in non-GL States suggests that existing controls limit pathogen spread, and that even spread via natural pathways (e.g., water movement or migratory fish) appears contained to the Great Lakes system. This report exemplifies the cost-effective use of risk-based surveillance in decision support to assess and manage aquatic animal population health in open systems. Published by Elsevier B.V.

Entolimod in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer Receiving Cisplatin and Radiation Therapy

ClinicalTrials.gov

2013-12-10

Mucositis; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Talactoferrin in Treating Patients With Relapsed or Refractory Non-Small Cell Lung Cancer or Squamous Cell Head and Neck Cancer

ClinicalTrials.gov

2016-07-30

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Chemical Genetics Reveals Bacterial and Host Cell Functions Critical for Type IV Effector Translocation by Legionella pneumophila

PubMed Central

Charpentier, Xavier; Gabay, Joëlle E.; Reyes, Moraima; Zhu, Jing W.; Weiss, Arthur; Shuman, Howard A.

2009-01-01

Delivery of effector proteins is a process widely used by bacterial pathogens to subvert host cell functions and cause disease. Effector delivery is achieved by elaborate injection devices and can often be triggered by environmental stimuli. However, effector export by the L. pneumophila Icm/Dot Type IVB secretion system cannot be detected until the bacterium encounters a target host cell. We used chemical genetics, a perturbation strategy that utilizes small molecule inhibitors, to determine the mechanisms critical for L. pneumophila Icm/Dot activity. From a collection of more than 2,500 annotated molecules we identified specific inhibitors of effector translocation. We found that L. pneumophila effector translocation in macrophages requires host cell factors known to be involved in phagocytosis such as phosphoinositide 3-kinases, actin and tubulin. Moreover, we found that L. pneumophila phagocytosis and effector translocation also specifically require the receptor protein tyrosine phosphate phosphatases CD45 and CD148. We further show that phagocytosis is required to trigger effector delivery unless intimate contact between the bacteria and the host is artificially generated. In addition, real-time analysis of effector translocation suggests that effector export is rate-limited by phagocytosis. We propose a model in which L. pneumophila utilizes phagocytosis to initiate an intimate contact event required for the translocation of pre-synthesized effector molecules. We discuss the need for host cell participation in the initial step of the infection and its implications in the L. pneumophila lifestyle. Chemical genetic screening provides a novel approach to probe the host cell functions and factors involved in host–pathogen interactions. PMID:19578436

Early Depositional History of the Eocene Izu-Bonin Mariana Arc, Western Pacific Ocean

NASA Astrophysics Data System (ADS)

Waldman, R.; Marsaglia, K. M.; Tepley, F. J., III

2015-12-01

Expedition 351 of the International Ocean Discovery Program cored an Eocene section at Site U1438 in the Philippine Sea that provides insight into the early history of the Izu-Bonin arc. Subduction here is hypothesized to have initiated spontaneously, leaving a characteristic depositional sequence of post-subduction-initiation localized extension and volcanism. We conducted detailed macroscopic and microscopic study of the cores of the lowermost 100m of volcaniclastic and sedimentary rocks (Unit IV) directly overlying subduction initiation igneous basement, to identify depositional facies and trends. We subdivided Unit IV into three subunits based on lithologic characteristics. Transitions between the subunits are relatively abrupt, occurring within the length of a single core. The lowermost subunit (IVA) consists of 4 meters of laminated pelagic claystone with thin beds of graded volcaniclastic siltstone, and fine-grained tuff laminae composed of plagioclase feldspar and green-brown amphibole. The middle subunit (IVB) comprises 51 meters of texturally variable, thick-bedded, coarse-grained gravity flow deposits. These are composed of volcaniclastic sandstone and conglomerate containing glassy and tachylitic volcanic grains as well as sedimentary lithic fragments, along with traces of shallow-water carbonate bioclasts. Subunit IVB sediments are poorer in feldspar than IVA and contain only trace amphibole. They show variable grain rounding and an upsection increase in vitric components. Tachylite grains range from sub-angular to well rounded throughout, and other volcanic grain types show upward increases in angularity and vesicularity. The abrupt transition from pelagic sediments in subunit IVA to shallow-water-sourced gravity flows in subunit IVB suggests a rapid emergence of shallow-water to subaerial volcanic center early in the arc's development. The upper part of subunit IVB also contains igneous intrusions, providing possible evidence for more proximal volcanism at the site. Subunit IVC consists of 46 meters of fine-grained turbidites composed of tuffaceous siltstone, along with radiolarian mudstone and vitric tuff layers. Ongoing studies of the volcanic components will provide additional insight into the source(s) of volcanics throughout the arc's early development.

ClpP-deletion impairs the virulence of Legionella pneumophila and the optimal translocation of effector proteins.

PubMed

Zhao, Bei-Bei; Li, Xiang-Hui; Zeng, Yong-Lun; Lu, Yong-Jun

2016-08-02

The opportunistic bacterial pathogen Legionella pneumophila uses substrate effectors of Dot/Icm type IVB secretion system (T4BSS) to accomplish survival and replication in amoebae cells and mammalian alveolar macrophages. During the conversion between its highly resistant, infectious dormant form and vigorously growing, uninfectious replicative form, L. pneumophila utilizes a complicated regulatory network in which proteolysis may play a significant role. As a highly conserved core protease, ClpP is involved in various cellular processes as well as virulence in bacteria, and has been proved to be required for the expression of transmission traits and cell division of L. pneumophila. The clpP-deficient L. pneumophila strain failed to replicate and was digested in the first 3 h post-infection in mammalian cells J774A.1. Further investigation demonstrates that the clpP deficient mutant strain was unable to escape the endosome-lysosomal pathway in host cells. We also found that the clpP deficient mutant strain still expresses T4BSS components, induces contact-dependent cytotoxicity and translocate effector proteins RalF and LegK2, indicating that its T4BSS was overall functional. Interestingly, we further found that the translocation of several effector proteins is significantly reduced without ClpP. The data indicate that ClpP plays an important role in regulating the virulence and effector translocation of Legionella pneumophila.

45 CFR 1357.20 - Child abuse and neglect programs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Child abuse and neglect programs. 1357.20 Section... APPLICABLE TO TITLE IV-B § 1357.20 Child abuse and neglect programs. The State agency must assure that, with regard to any child abuse and neglect programs or projects funded under title IV-B of the Act, the...

45 CFR 1355.21 - Plan requirements for titles IV-E and IV-B.

Code of Federal Regulations, 2012 CFR

2012-10-01

... agency and the Indian Tribe must make available for public review and inspection the Child and Family... 45 Public Welfare 4 2012-10-01 2012-10-01 false Plan requirements for titles IV-E and IV-B. 1355.21 Section 1355.21 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN...

45 CFR 1355.21 - State plan requirements for titles IV-E and IV-B.

Code of Federal Regulations, 2011 CFR

2011-10-01

... and the Indian Tribe must make available for public review and inspection the Child and Family... 45 Public Welfare 4 2011-10-01 2011-10-01 false State plan requirements for titles IV-E and IV-B. 1355.21 Section 1355.21 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF...

45 CFR 1355.21 - Plan requirements for titles IV-E and IV-B.

Code of Federal Regulations, 2014 CFR

2014-10-01

... agency and the Indian Tribe must make available for public review and inspection the Child and Family... 45 Public Welfare 4 2014-10-01 2014-10-01 false Plan requirements for titles IV-E and IV-B. 1355.21 Section 1355.21 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN...

Irinotecan-Eluting Beads in Treating Patients With Refractory Metastatic Colon or Rectal Cancer That Has Spread to the Liver

ClinicalTrials.gov

2018-02-22

Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

45 CFR 1357.32 - State fiscal requirements (title IV-B, subpart 2, family preservation and family support services).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false State fiscal requirements (title IV-B, subpart 2, family preservation and family support services). 1357.32 Section 1357.32 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN...

45 CFR 1357.32 - State fiscal requirements (title IV-B, subpart 2, family preservation and family support services).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false State fiscal requirements (title IV-B, subpart 2, family preservation and family support services). 1357.32 Section 1357.32 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN...

45 CFR 1357.32 - State fiscal requirements (title IV-B, subpart 2, family preservation and family support services).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false State fiscal requirements (title IV-B, subpart 2, family preservation and family support services). 1357.32 Section 1357.32 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN...

45 CFR 1357.32 - State fiscal requirements (title IV-B, subpart 2, family preservation and family support services).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false State fiscal requirements (title IV-B, subpart 2, family preservation and family support services). 1357.32 Section 1357.32 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN...

Complete sequences of 4 viral hemorrhagic septicemia virus IVb isolates and their virulence in northern pike fry.

PubMed

Getchell, Rodman G; Cornwell, Emily R; Bogdanowicz, Steven; Andrés, Jose; Batts, William N; Kurath, Gael; Breyta, Rachel; Choi, Joanna G; Farrell, John M; Bowser, Paul R

2017-11-21

Four viral hemorrhagic septicemia virus (VHSV) genotype IVb isolates were sequenced, their genetic variation explored, and comparative virulence assayed with experimental infections of northern pike Esox lucius fry. In addition to the type strain MI03, the complete 11183 bp genome of the first round goby Neogobius melanostomus isolate from the St. Lawrence River, and the 2013 and 2014 isolates from gizzard shad Dorosoma cepedianum die-offs in Irondequoit Bay, Lake Ontario and Dunkirk Harbor, Lake Erie were all deep sequenced on an Illumina platform. Mutations documented in the 11 yr since the MI03 index case from Lake St. Clair muskellunge Esox masquinongy showed 87 polymorphisms among the 4 isolates. Twenty-six mutations were non-synonymous and located at 18 different positions within the matrix protein, glycoprotein, non-virion protein, and RNA polymerase genes. The same 4 isolates were used to infect northern pike fry by a single 1 h bath exposure. Cumulative percent mortality varied from 42.5 to 62.5%. VHSV was detected in 57% (41/72) of the survivors at the end of the 21-d trial, suggesting that the virus was not rapidly cleared. Lesions were observed in many of the moribund and dead northern pike, such as hemorrhaging in the skin and fins, as well as hydrocephalus. Mean viral load measured from the trunk and visceral tissues of MI03-infected pike was significantly higher than the quantities detected in fish infected with the most recent isolates of genotype IVb, but there were no differences in cumulative mortality observed.

Natural variations in the rhenium isotopic composition of meteorites

NASA Astrophysics Data System (ADS)

Liu, R.; Hu, L.; Humayun, M.

2017-03-01

Rhenium is an important element with which to test hypotheses of isotope variation. Historically, it has been difficult to precisely correct the instrumental mass bias in thermal ionization mass spectrometry. We used W as an internal standard to correct mass bias on the MC-ICP-MS, and obtained the first precise δ187Re values ( ±0.02‰, 2SE) for iron meteorites and chondritic metal. Relative to metal from H chondrites, IVB irons are systematically higher in δ187Re by 0.14 ‰. δ187Re for other irons are similar to H chondritic metal, although some individual samples show significant isotope fractionation. Since 185Re has a high neutron capture cross section, the effect of galactic cosmic-ray (GCR) irradiation on δ187Re was examined using correlations with Pt isotopes. The pre-GCR irradiation δ187Re for IVB irons is lower, but the difference in δ187Re between IVB irons and other meteoritic metal remains. Nuclear volume-dependent fractionation for Re is about the right magnitude near the melting point of iron, but because of the refractory and compatible character of Re, a compelling explanation in terms of mass-dependent fractionation is elusive. The magnitude of a nucleosynthetic s-process deficit for Re estimated from Mo and Ru isotopes is essentially unresolvable. Since thermal processing reduced nucleosynthetic effects in Pd, it is conceivable that Re isotopic variations larger than those in Mo and Ru may be present in IVBs since Re is more refractory than Mo and Ru. Thus, the Re isotopic difference between IVBs and other irons or chondritic metal remains unexplained.

APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-03-29

Metastatic Malignant Neoplasm in the Brain; Metastatic Solid Neoplasm; Recurrent Colorectal Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Solid Neoplasm; Stage IV Colorectal Cancer; Stage IV Pancreatic Cancer; Stage IVA Colorectal Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Pancreatic Cancer; Unresectable Solid Neoplasm

Saturn Apollo Program

NASA Image and Video Library

1967-01-01

The Saturn IB S-IVB (second) stages in storage at the Douglas Aircraft Company's Sacramento Test Operations Facility (SACTO) in Sacramento, California. Designed and developed by the Marshall Space Flight Center and the Douglas Aircraft Company, the S-IVB stage was powered by a single J-2 engine, which produced 200,000 pounds of thrust, later uprated to 230,000 pounds for the Saturn V launch vehicle.

Acetylcysteine Rinse in Reducing Saliva Thickness and Mucositis in Patients With Head and Neck Cancer Undergoing Radiation Therapy

ClinicalTrials.gov

2018-04-17

Mucositis; Oral Complications; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Adenoid Cystic Carcinoma of the Oral Cavity; Stage II Basal Cell Carcinoma of the Lip; Stage II Lymphoepithelioma of the Nasopharynx; Stage II Lymphoepithelioma of the Oropharynx; Stage II Mucoepidermoid Carcinoma of the Oral Cavity; Stage II Salivary Gland Cancer; Stage II Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Larynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Basal Cell Carcinoma of the Lip; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Lymphoepithelioma of the Oropharynx; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVA Basal Cell Carcinoma of the Lip; Stage IVA Lymphoepithelioma of the Oropharynx; Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVB Basal Cell Carcinoma of the Lip; Stage IVB Lymphoepithelioma of the Oropharynx; Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVC Basal Cell Carcinoma of the Lip; Stage IVC Lymphoepithelioma of the Oropharynx; Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

View of the Saturn V third stage from which the Apollo 8 has separated

NASA Image and Video Library

1968-12-21

AS08-16-2582 (21 Dec. 1968) --- This is a photograph taken from the Apollo 8 spacecraft looking back at the Saturn V third (S-IVB) stage from which the spacecraft had just separated following trans-lunar injection. (Hold picture with S-IVB at top center). Attached to the S-IVB is the Lunar Module Test Article (LTA) which simulated the mass of a Lunar Module (LM) on the Apollo 8 lunar orbit mission. The 29-feet panels of the Spacecraft LM Adapter which enclosed the LTA during launch have already been jettisoned and are out of view. Sunlight reflected from small particles shows the "firefly" phenomenon which was reported by astronaut John H. Glenn Jr. during the first Earth-orbital flight (Mercury-Atlas 6) of the Mercury Program.

Paclitaxel and Carboplatin Before Radiation Therapy With Paclitaxel in Treating HPV-Positive Patients With Stage III-IV Oropharynx, Hypopharynx, or Larynx Cancer

ClinicalTrials.gov

2017-04-19

Human Papilloma Virus Infection; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Larynx

Multistage Core Formation in Planetesimals Revealed by Numerical Modeling and Hf-W Chronometry of Iron Meteorites

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

Neumann, W.; Kruijer, T. S.; Breuer, D.

Iron meteorites provide some of the most direct insights into the processes and timescales of core formation in planetesimals. Of these, group IVB irons stand out by having one of the youngest 182Hf- 182W model ages for metal segregation (2.9 ± 0.6 Ma after solar system formation), as well as the lowest bulk sulfur content and hence highest liquidus temperature. Here in this paper, using a new model for the internal evolution of the IVB parent body, we show that a single stage of metal-silicate separation cannot account for the complete melting of pure Fe metal at the relatively latemore » time given by the Hf-W model age. Instead, a complex metal-silicate separation scenario is required that includes migration of partial silicate melts, formation of a shallow magma ocean, and core formation in two distinct stages of metal segregation. In the first stage, a protocore formed at ≈1.5 Ma via settling of metal particles in a mantle magma ocean, followed by metal segregation from a shallow magma ocean at ≈5.4 Ma. As these stages of metal segregation occurred at different times, the two metal fractions had different 182W compositions. Consequently, the final 182W composition of the IVB core does not correspond to a single differentiation event, but represents the average composition of early- and late-segregated core fractions. Our best fit model indicates an ≈100 km radius for the IVB parent body and provides an accretion age of ≈0.1–0.5 Ma after solar system formation. The computed solidification time is, furthermore, consistent with the Re-Os age for crystallization of the IVB core.« less

Multistage Core Formation in Planetesimals Revealed by Numerical Modeling and Hf-W Chronometry of Iron Meteorites

DOE PAGES

Neumann, W.; Kruijer, T. S.; Breuer, D.; ...

2018-02-01

Iron meteorites provide some of the most direct insights into the processes and timescales of core formation in planetesimals. Of these, group IVB irons stand out by having one of the youngest 182Hf- 182W model ages for metal segregation (2.9 ± 0.6 Ma after solar system formation), as well as the lowest bulk sulfur content and hence highest liquidus temperature. Here in this paper, using a new model for the internal evolution of the IVB parent body, we show that a single stage of metal-silicate separation cannot account for the complete melting of pure Fe metal at the relatively latemore » time given by the Hf-W model age. Instead, a complex metal-silicate separation scenario is required that includes migration of partial silicate melts, formation of a shallow magma ocean, and core formation in two distinct stages of metal segregation. In the first stage, a protocore formed at ≈1.5 Ma via settling of metal particles in a mantle magma ocean, followed by metal segregation from a shallow magma ocean at ≈5.4 Ma. As these stages of metal segregation occurred at different times, the two metal fractions had different 182W compositions. Consequently, the final 182W composition of the IVB core does not correspond to a single differentiation event, but represents the average composition of early- and late-segregated core fractions. Our best fit model indicates an ≈100 km radius for the IVB parent body and provides an accretion age of ≈0.1–0.5 Ma after solar system formation. The computed solidification time is, furthermore, consistent with the Re-Os age for crystallization of the IVB core.« less

Reducing intraocular-pressure spike after intravitreal-bevacizumab injection with ocular decompression using a sterile cotton swab soaked in proparacaine 0.5%: A quasi-experimental study.

PubMed

Qureshi, Naveed A; Mansoor, Hassan; Ahmad, Sabihuddin; Zafar, Sarah; Asif, Muhammad

2016-01-01

The study was conducted to determine the effect of preinjection ocular decompression by a cotton swab soaked in local anesthetic on the immediate postinjection rise in intraocular pressure (IOP) after intravitreal bevacizumab (IVB). A nonrandomized, quasi-experimental interventional study was conducted at Al-Shifa Trust Eye Hospital, Pakistan, from August 1, 2013 to July 31, 2014. One hundred ( n = 100) patients receiving 0.05-mL IVB injection for the first time were assigned to two preinjection anesthetic methods: one with ocular decompression using a sterile cotton swab soaked in proparacaine 0.5%, and the other without ocular decompression using proparacaine 0.5% eyedrops. The IOP was recorded in the eye receiving IVB at three time intervals: Time 1 (preinjection), Time 2 (immediately after injection), and Time 3 (30 minutes after injection). There was a significant difference in the mean IOP change (between Time 1 and Time 2) for the group injected with ocular decompression [ M = 1.00, standard deviation (SD) = 1.47] and the group injected without ocular decompression ( M = 5.00, SD = 2.38; t (68) = 9.761, p < 0.001). There was also a significant difference in the mean IOP change (between Time 1 and Time 3) for the group injected with ocular decompression ( M = 0.428, SD = 1.58) and the group injected without ocular decompression ( M = 4.318, SD = 3.34; t (58) = 7.111, p < 0.001). Patients receiving IVB injections with ocular-decompression soaking in proparacaine 0.5% experience significantly lower postinjection IOP spike, and that too for a considerably shorter duration as compared to those receiving IVB without ocular decompression.

Multistage Core Formation in Planetesimals Revealed by Numerical Modeling and Hf-W Chronometry of Iron Meteorites

NASA Astrophysics Data System (ADS)

Neumann, W.; Kruijer, T. S.; Breuer, D.; Kleine, T.

2018-02-01

Iron meteorites provide some of the most direct insights into the processes and timescales of core formation in planetesimals. Of these, group IVB irons stand out by having one of the youngest 182Hf-182W model ages for metal segregation (2.9 ± 0.6 Ma after solar system formation), as well as the lowest bulk sulfur content and hence highest liquidus temperature. Here, using a new model for the internal evolution of the IVB parent body, we show that a single stage of metal-silicate separation cannot account for the complete melting of pure Fe metal at the relatively late time given by the Hf-W model age. Instead, a complex metal-silicate separation scenario is required that includes migration of partial silicate melts, formation of a shallow magma ocean, and core formation in two distinct stages of metal segregation. In the first stage, a protocore formed at ≈1.5 Ma via settling of metal particles in a mantle magma ocean, followed by metal segregation from a shallow magma ocean at ≈5.4 Ma. As these stages of metal segregation occurred at different times, the two metal fractions had different 182W compositions. Consequently, the final 182W composition of the IVB core does not correspond to a single differentiation event, but represents the average composition of early- and late-segregated core fractions. Our best fit model indicates an ≈100 km radius for the IVB parent body and provides an accretion age of ≈0.1-0.5 Ma after solar system formation. The computed solidification time is, furthermore, consistent with the Re-Os age for crystallization of the IVB core.

Complete sequences of 4 viral hemorrhagic septicemia virus IVb isolates and their virulence in northern pike fry

USGS Publications Warehouse

Getchell, Rodman G.; Cornwell, Emily R.; Bogdanowicz, Steven; Andres, Jose; Batts, William N.; Kurath, Gael; Breyta, Rachel; Choi, Joanna G.; Farrell, John M.; Bowser, Paul R.

2017-01-01

Four viral hemorrhagic septicemia virus (VHSV) genotype IVb isolates were sequenced, their genetic variation explored, and comparative virulence assayed with experimental infections of northern pike Esox lucius fry. In addition to the type strain MI03, the complete 11183 bp genome of the first round goby Neogobius melanostomus isolate from the St. Lawrence River, and the 2013 and 2014 isolates from gizzard shad Dorosoma cepedianum die-offs in Irondequoit Bay, Lake Ontario and Dunkirk Harbor, Lake Erie were all deep sequenced on an Illumina platform. Mutations documented in the 11 yr since the MI03 index case from Lake St. Clair muskellunge Esox masquinongy showed 87 polymorphisms among the 4 isolates. Twenty-six mutations were non-synonymous and located at 18 different positions within the matrix protein, glycoprotein, non-virion protein, and RNA polymerase genes. The same 4 isolates were used to infect northern pike fry by a single 1 h bath exposure. Cumulative percent mortality varied from 42.5 to 62.5%. VHSV was detected in 57% (41/72) of the survivors at the end of the 21-d trial, suggesting that the virus was not rapidly cleared. Lesions were observed in many of the moribund and dead northern pike, such as hemorrhaging in the skin and fins, as well as hydrocephalus. Mean viral load measured from the trunk and visceral tissues of MI03-infected pike was significantly higher than the quantities detected in fish infected with the most recent isolates of genotype IVb, but there were no differences in cumulative mortality observed.

Electronic Monitoring Device of Patient-Reported Outcomes and Function in Improving Patient-Centered Care in Patients With Gastrointestinal Cancer Undergoing Surgery

ClinicalTrials.gov

2018-06-06

Stage I Adult Liver Cancer; Stage I Colorectal Cancer; Stage IA Gastric Cancer; Stage IA Pancreatic Cancer; Stage IB Gastric Cancer; Stage IB Pancreatic Cancer; Stage II Adult Liver Cancer; Stage IIA Colorectal Cancer; Stage IIA Gastric Cancer; Stage IIA Pancreatic Cancer; Stage IIB Colorectal Cancer; Stage IIB Gastric Cancer; Stage IIB Pancreatic Cancer; Stage IIC Colorectal Cancer; Stage III Pancreatic Cancer; Stage IIIA Adult Liver Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Adult Liver Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Adult Liver Cancer; Stage IIIC Colorectal Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer; Stage IVA Colorectal Cancer; Stage IVA Liver Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Liver Cancer; Stage IVB Pancreatic Cancer

Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer

ClinicalTrials.gov

2018-05-15

Metastatic Thyroid Gland Carcinoma; Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

[Crops: Classifying, Selecting, Harvesting, Grading, and Packing.] Student Materials. V.A. III. [IV-B-1 through IV-B-2; IV-C-1 through IV-C-2].

ERIC Educational Resources Information Center

Texas A and M Univ., College Station. Vocational Instructional Services.

Part of a series of eight student learning modules in vocational agriculture, this booklet deals with crop-related activities. The first section is on harvesting methods and equipment. The following portions address the handling, grading, and packing of crops; and the classification and selection of fruits, vegetables, and ornamental plants. There…

Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

ClinicalTrials.gov

2017-11-15

Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Pan FGFR Kinase Inhibitor BGJ398 and Combination Chemotherapy in Treating Patients With Untreated Metastatic Pancreatic Cancer

ClinicalTrials.gov

2016-05-19

Colon Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Rectal Adenocarcinoma; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Aft View of Saturn V Third Stage (S-IVB)

NASA Technical Reports Server (NTRS)

1960-01-01

The powerful J-2 engine is prominent in this photograph of a Saturn V Third Stage (S-IVB) resting on a transporter in the Manufacturing Facility at Marshall Space Flight Center in Huntsville, Alabama. The towering 363-foot Saturn V was a multi-stage, multi-engine launch vehicle standing taller than the Statue of Liberty. Altogether, the Saturn V engines produced as much power as 85 Hoover Dams.

Saturn Apollo Program

NASA Image and Video Library

1968-01-01

This cutaway drawing shows the S-IVB stage in its Saturn IB configuration. As a part of the Marshall Space Flight Center's (MSFC) "building block" approach to the Saturn development, the S-IVB stage was utilized in the Saturn IB launch vehicle as a second stage and, later, the Saturn V launch vehicle as a third stage. The stage was powered by a single J-2 engine, initially capable of 200,000 pounds of thrust.

Prepare to Care, A Supported Self-Management Intervention for Head and Neck Cancer CaregiversHead and Neck Cancer

ClinicalTrials.gov

2018-04-26

Caregiver; Malignant Head and Neck Neoplasm; Paranasal Sinus Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage I Hypopharyngeal Squamous Cell Carcinoma; Stage I Laryngeal Squamous Cell Carcinoma; Stage I Lip and Oral Cavity Squamous Cell Carcinoma; Stage I Oropharyngeal Squamous Cell Carcinoma; Stage II Hypopharyngeal Squamous Cell Carcinoma; Stage II Laryngeal Squamous Cell Carcinoma; Stage II Lip and Oral Cavity Squamous Cell Carcinoma; Stage II Oropharyngeal Squamous Cell Carcinoma; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Lip and Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IV Laryngeal Squamous Cell Carcinoma; Stage IV Lip and Oral Cavity Squamous Cell Carcinoma; Stage IV Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Hypopharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

Vaginal Microbiota and Sexually Transmitted Infections That May Influence Transmission of Cell-Associated HIV

PubMed Central

Cone, Richard A.

2014-01-01

Vaginal microbiota and sexually transmitted infections (STIs) are likely to influence the transmission of cell-associated human immunodeficiency virus (HIV). Lactic acid produced by Lactobacillus-dominated microbiota (Nugent score 0–3) will likely inhibit transmission, especially female-to-male transmission. In contrast, polymicrobial microbiota (Nugent score 4–10), community state types IV-A and IV-B, and STIs will likely increase transmission of cell-associated HIV. PMID:25414415

Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer

ClinicalTrials.gov

2013-05-01

Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Programs to Support You During Chemotherapy (Pro-You)

ClinicalTrials.gov

2015-06-19

Depressive Symptoms; Fatigue; Psychosocial Effects of Cancer and Its Treatment; Stage IIA Colon Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Saturn Apollo Program

NASA Image and Video Library

1967-01-01

Workmen secure a J-2 engine onto the S-IVB (second) stage thrust structure. As part of Marshall Space Center's "building block" approach to the Saturn development, the S-IVB was utilized in the Saturn IBC launch vehicle as a second stage and the Saturn V launch vehicle as a third stage. The booster, built for NASA by McDornell Douglas Corporation, was powered by a single J-2 engine, initially capable of 200,000 pounds of thrust.

Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer

ClinicalTrials.gov

2018-04-11

Adenocarcinoma of the Gastroesophageal Junction; Colorectal Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Non-Resectable Hepatocellular Carcinoma; Recurrent Cholangiocarcinoma; Recurrent Colorectal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Small Intestinal Carcinoma; Small Intestinal Adenocarcinoma; Stage III Colorectal Cancer; Stage III Gastric Cancer; Stage III Hepatocellular Carcinoma; Stage III Pancreatic Cancer; Stage III Small Intestinal Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Hepatocellular Carcinoma; Stage IIIA Small Intestinal Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Hepatocellular Carcinoma; Stage IIIB Small Intestinal Cancer; Stage IIIC Gastric Cancer; Stage IV Colorectal Cancer; Stage IV Gastric Cancer; Stage IV Hepatocellular Carcinoma; Stage IV Pancreatic Cancer; Stage IV Small Intestinal Cancer; Stage IVA Colorectal Cancer; Stage IVA Hepatocellular Carcinoma; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Hepatocellular Carcinoma; Stage IVB Pancreatic Cancer; Unresectable Pancreatic Carcinoma; Unresectable Small Intestinal Carcinoma

Lenvatinib and Pembrolizumab in DTC

ClinicalTrials.gov

2018-05-21

Columnar Cell Variant Thyroid Gland Papillary Carcinoma; Follicular Variant Thyroid Gland Papillary Carcinoma; Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma AJCC v7; Stage III Thyroid Gland Follicular Carcinoma AJCC v7; Stage III Thyroid Gland Papillary Carcinoma AJCC v7; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7; Tall Cell Variant Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma

Comparison of LiST measles mortality model and WHO/IVB measles model.

PubMed

Chen, Wei-Ju

2011-04-13

The Lives Saved Tool (LiST) has been developed to estimate the impact of health interventions and can consider multiple interventions simultaneously. Given its increasing usage by donor organizations and national program planner, we compare the LiST measles model to the widely used World Health Organization's Department of Immunization, Vaccines and Biologicals (WHO/IVB) measles model which is used to produce estimates serving as a major indicator of monitoring country measles epidemics and the progress of measles control. We analyzed the WHO/IVB models and the LiST measles model and identified components and assumptions held in each model. We contrasted the important components, and compared results from the two models by applying historical measles containing vaccine (MCV) coverages and the default values of all parameters set in the models. We also conducted analyses following a hypothetical scenario to understand how both models performed when the proportion of population protected by MCV declined to zero percent in short time period. The WHO/IVB measles model and the LiST measles model structures differ: the former is a mixed model which applies surveillance data adjusted for reporting completeness for countries with good disease surveillance system and applies a natural history model for countries with poorer disease control program and surveillance system, and the latter is a cohort model incorporating country-specific cause-of-death (CoD) profiles among children under-five. The trends of estimates of the two models are similar, but the estimates of the first year are different in most of the countries included in the analysis. The two models are comparable if we adjust the measles CoD in the LiST to produce the same baseline estimates. In addition, we used the models to estimate the potential impact of stopping using measles vaccine over a 7-year period. The WHO/IVB model produced similar estimates to the LiST model with adjusted CoD. But the LiST model produced low estimates for countries with very low or eliminated measles infection that may be inappropriate. The study presents methodological and quantitative comparisons between the WHO/IVB and the LiST measles models that highlights differences in model structures and may help users to better interpret and contrast estimates of the measles death from the two models. The major differences are resulted from the usage of case-fatality rate (CFR) in the WHO/IVB model and the CoD profile in the LiST. Both models have their own advantages and limitations. Users should be aware of the issue and apply as update country parameters as possible. Advanced models are expected to validate the policy-planning tools in the future.

Comparison of LiST measles mortality model and WHO/IVB measles model

PubMed Central

2011-01-01

Background The Lives Saved Tool (LiST) has been developed to estimate the impact of health interventions and can consider multiple interventions simultaneously. Given its increasing usage by donor organizations and national program planner, we compare the LiST measles model to the widely used World Health Organization's Department of Immunization, Vaccines and Biologicals (WHO/IVB) measles model which is used to produce estimates serving as a major indicator of monitoring country measles epidemics and the progress of measles control. Methods We analyzed the WHO/IVB models and the LiST measles model and identified components and assumptions held in each model. We contrasted the important components, and compared results from the two models by applying historical measles containing vaccine (MCV) coverages and the default values of all parameters set in the models. We also conducted analyses following a hypothetical scenario to understand how both models performed when the proportion of population protected by MCV declined to zero percent in short time period. Results The WHO/IVB measles model and the LiST measles model structures differ: the former is a mixed model which applies surveillance data adjusted for reporting completeness for countries with good disease surveillance system and applies a natural history model for countries with poorer disease control program and surveillance system, and the latter is a cohort model incorporating country-specific cause-of-death (CoD) profiles among children under-five. The trends of estimates of the two models are similar, but the estimates of the first year are different in most of the countries included in the analysis. The two models are comparable if we adjust the measles CoD in the LiST to produce the same baseline estimates. In addition, we used the models to estimate the potential impact of stopping using measles vaccine over a 7-year period. The WHO/IVB model produced similar estimates to the LiST model with adjusted CoD. But the LiST model produced low estimates for countries with very low or eliminated measles infection that may be inappropriate. Conclusions The study presents methodological and quantitative comparisons between the WHO/IVB and the LiST measles models that highlights differences in model structures and may help users to better interpret and contrast estimates of the measles death from the two models. The major differences are resulted from the usage of case-fatality rate (CFR) in the WHO/IVB model and the CoD profile in the LiST. Both models have their own advantages and limitations. Users should be aware of the issue and apply as update country parameters as possible. Advanced models are expected to validate the policy-planning tools in the future. PMID:21501452

Phase 1b Food Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer.

ClinicalTrials.gov

2018-03-05

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage 0 Hypopharyngeal Cancer; Stage 0 Laryngeal Cancer; Stage 0 Lip and Oral Cavity Cancer; Stage 0 Nasopharyngeal Cancer; Stage 0 Oropharyngeal Cancer; Stage 0 Paranasal Sinus and Nasal Cavity Cancer; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Salivary Gland Cancer; Stage II Squamous Cell Carcinoma of the Hypopharynx; Stage II Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage II Verrucous Carcinoma of the Larynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Nasal Cavity and Paranasal Sinus Cancer; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Oral Cavity Squamous Cell Carcinoma; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Paranasal Sinus and Nasal Cavity Squamous Cell Carcinoma; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

A Legionella Effector Disrupts Host Cytoskeletal Structure by Cleaving Actin

DOE PAGES

Liu, Yao; Zhu, Wenhan; Tan, Yunhao; ...

2017-01-27

Legionella pneumophila, the etiological agent of Legionnaires' disease, replicates intracellularly in protozoan and human hosts. Successful colonization and replication of this pathogen in host cells requires the Dot/Icm type IVB secretion system, which translocates approximately 300 effector proteins into the host cell to modulate various cellular processes. In this study, we identified RavK as a Dot/Icm substrate that targets the host cytoskeleton and reduces actin filament abundance in mammalian cells upon ectopic expression. RavK harbors an H 95E XXH 99 motif associated with diverse metalloproteases, which is essential for the inhibition of yeast growth and for the induction of cellmore » rounding in HEK293T cells. We demonstrate that the actin protein itself is the cellular target of RavK and that this effector cleaves actin at a site between residues Thr351 and Phe352. Importantly, RavK-mediated actin cleavage also occurs during L. pneumophila infection. Cleavage by RavK abolishes the ability of actin to form polymers. Furthermore, an F352A mutation renders actin resistant to RavK-mediated cleavage; expression of the mutant in mammalian cells suppresses the cell rounding phenotype caused by RavK, further establishing that actin is the physiological substrate of RavK. Furthermore, L. pneumophila exploits components of the host cytoskeleton by multiple effectors with distinct mechanisms, highlighting the importance of modulating cellular processes governed by the actin cytoskeleton in the intracellular life cycle of this pathogen.« less

Legionella pneumophila strain associated with the first evidence of person-to-person transmission of Legionnaires’ disease: a unique mosaic genetic backbone

PubMed Central

Borges, Vítor; Nunes, Alexandra; Sampaio, Daniel A.; Vieira, Luís; Machado, Jorge; Simões, Maria J.; Gonçalves, Paulo; Gomes, João P.

2016-01-01

A first strong evidence of person-to-person transmission of Legionnaires’ Disease (LD) was recently reported. Here, we characterize the genetic backbone of this case-related Legionella pneumophila strain (“PtVFX/2014”), which also caused a large outbreak of LD. PtVFX/2014 is phylogenetically divergent from the most worldwide studied outbreak-associated L. pneumophila subspecies pneumophila serogroup 1 strains. In fact, this strain is also from serogroup 1, but belongs to the L. pneumophila subspecies fraseri. Its genomic mosaic backbone reveals eight horizontally transferred regions encompassing genes, for instance, involved in lipopolysaccharide biosynthesis or encoding virulence-associated Dot/Icm type IVB secretion system (T4BSS) substrates. PtVFX/2014 also inherited a rare ~65 kb pathogenicity island carrying virulence factors and detoxifying enzymes believed to contribute to the emergence of best-fitted strains in water reservoirs and in human macrophages, as well as a inter-species transferred (from L. oakridgensis) ~37.5 kb genomic island (harboring a lvh/lvr T4ASS cluster) that had never been found intact within L. pneumophila species. PtVFX/2014 encodes another lvh/lvr cluster near to CRISPR-associated genes, which may boost L. pneumophila transition from an environmental bacterium to a human pathogen. Overall, this unique genomic make-up may impact PtVFX/2014 ability to adapt to diverse environments, and, ultimately, to be transmitted and cause human disease. PMID:27196677

AtlA functions as a peptidoglycan lytic transglycosylase in the Neisseria gonorrhoeae type IV secretion system.

PubMed

Kohler, Petra L; Hamilton, Holly L; Cloud-Hansen, Karen; Dillard, Joseph P

2007-08-01

Type IV secretion systems require peptidoglycan lytic transglycosylases for efficient secretion, but the function of these enzymes is not clear. The type IV secretion system gene cluster of Neisseria gonorrhoeae encodes two peptidoglycan transglycosylase homologues. One, LtgX, is similar to peptidoglycan transglycosylases from other type IV secretion systems. The other, AtlA, is similar to endolysins from bacteriophages and is not similar to any described type IV secretion component. We characterized the enzymatic function of AtlA in order to examine its role in the type IV secretion system. Purified AtlA was found to degrade macromolecular peptidoglycan and to produce 1,6-anhydro peptidoglycan monomers, characteristic of lytic transglycosylase activity. We found that AtlA can functionally replace the lambda endolysin to lyse Escherichia coli. In contrast, a sensitive measure of lysis demonstrated that AtlA does not lyse gonococci expressing it or gonococci cocultured with an AtlA-expressing strain. The gonococcal type IV secretion system secretes DNA during growth. A deletion of ltgX or a substitution in the putative active site of AtlA severely decreased DNA secretion. These results indicate that AtlA and LtgX are actively involved in type IV secretion and that AtlA is not involved in lysis of gonococci to release DNA. This is the first demonstration that a type IV secretion peptidoglycanase has lytic transglycosylase activity. These data show that AtlA plays a role in type IV secretion of DNA that requires peptidoglycan breakdown without cell lysis.

Secretion of TcpF by the Vibrio cholerae Toxin-Coregulated Pilus Biogenesis Apparatus Requires an N-Terminal Determinant

PubMed Central

Megli, Christina J.

2013-01-01

Type IV pili are important for microcolony formation, biofilm formation, twitching motility, and attachment. We and others have shown that type IV pili are important for protein secretion across the outer membrane, similar to type II secretion systems. This study explored the relationship between protein secretion and pilus formation in Vibrio cholerae. The toxin-coregulated pilus (TCP), a type IV pilus required for V. cholerae pathogenesis, is necessary for the secretion of the colonization factor TcpF (T. J. Kirn, N. Bose, and R. K. Taylor, Mol. Microbiol. 49:81–92, 2003). This phenomenon is not unique to V. cholerae; secreted virulence factors that are dependent on the presence of components of the type IV pilus biogenesis apparatus for secretion have been reported with Dichelobacter nodosus (R. M. Kennan, O. P. Dhungyel, R. J. Whittington, J. R. Egerton, and J. I. Rood, J. Bacteriol. 183:4451–4458, 2001) and Francisella tularensis (A. J. Hager et al., Mol. Microbiol. 62:227–237, 2006). Using site-directed mutagenesis, we demonstrated that the secretion of TcpF is dependent on the presence of selected amino acid R groups at position five. We were unable to find other secretion determinants, suggesting that Y5 is the major secretion determinant within TcpF. We also report that proteins secreted in a type IV pilus biogenesis apparatus-dependent manner have a YXS motif within the first 15 amino acids following the Sec cleavage site. The YXS motif is not present in proteins secreted by type II secretion systems, indicating that this is unique to type IV pilus-mediated secretion. Moreover, we show that TcpF interacts with the pilin TcpA, suggesting that these proteins are secreted by the type IV pilus biogenesis system. These data provide a starting point for understanding how type IV pili can mediate secretion of virulence factors important for bacterial pathogenesis. PMID:23564177

Durvalumab Before Surgery in Treating Patients With Oral Cavity or Oropharynx Cancer

ClinicalTrials.gov

2017-12-20

Human Papillomavirus Infection; Stage I Oral Cavity Squamous Cell Carcinoma; Stage I Oropharyngeal Squamous Cell Carcinoma; Stage II Oral Cavity Squamous Cell Carcinoma; Stage II Oropharyngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

CPI-613 and Fluorouracil in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-04-26

Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Ficlatuzumab With or Without Cetuximab in Treating Patients With Cetuximab-Resistant, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-02-02

Head and Neck Basaloid Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage IV Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Head and Neck Cancer; Oropharyngeal Cancer; HNSCC

Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up

PubMed Central

FAGHIHI, Hooshang; YAHYAPOUR, Hanif; MAHMOUDZADEH, Raziyeh; FAGHIHI, Shahin

2017-01-01

The aim of this study was to compare the effect of intravitreal diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with that of bevacizumab, a well-known anti-vascular endothelial growth factor (VEGF) drug, in the treatment of diabetic macular edema (DME). Diclofenac was chosen in this study because it has both features of NSAIDs and corticosteroids by inhibiting the cyclooxygenase (COX) and lipoxygenase pathways, respectively. In this non-randomized comparative interventional case series, 64 eyes from 32 patients with bilateral naïve DME were selected and every eye was randomly assigned to intravitreal injection of bevacizumab (IVB) or diclofenac (IVD). After exclusion of some patients because of short follow-up duration or less than two intravitreal injections, finally, 52 eyes from 26 patients were analyzed. Of those, 26 eyes received 500 µg/0.1 mL IVD and 26 eyes received 1.25 mg IVB. After 6 months of follow-up, the results indicated that visual acuity was significantly improved from 0.50 ± 0.13 in IVB and 0.52 ± 0.12 LogMAR in IVD at baseline to 0.2 ± 0.1 and 0.29 ± 0.07, respectively. Central macular thickness (CMT) and macular volume were measured based on spectral-domain optical coherence tomography (OCT) at month 1, 3, and 6. Both groups showed a significant reduction in CMT and macular volume from baseline but there was no significant difference between the IVB and IVD groups. Interestingly, IVD, but not IVB, decreased intraocular pressure (IOP), which is a desirable effect. There was no serious complication due to injections. This study sheds light into the long-term effects of NSAIDs and may support the idea that inflammation suppression by NSAIDs may have the same results as anti-VEGF administration. PMID:29392145

Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up.

PubMed

Faghihi, Hooshang; Yahyapour, Hanif; Mahmoudzadeh, Raziyeh; Faghihi, Shahin

2017-01-01

The aim of this study was to compare the effect of intravitreal diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with that of bevacizumab, a well-known anti-vascular endothelial growth factor (VEGF) drug, in the treatment of diabetic macular edema (DME). Diclofenac was chosen in this study because it has both features of NSAIDs and corticosteroids by inhibiting the cyclooxygenase (COX) and lipoxygenase pathways, respectively. In this non-randomized comparative interventional case series, 64 eyes from 32 patients with bilateral naïve DME were selected and every eye was randomly assigned to intravitreal injection of bevacizumab (IVB) or diclofenac (IVD). After exclusion of some patients because of short follow-up duration or less than two intravitreal injections, finally, 52 eyes from 26 patients were analyzed. Of those, 26 eyes received 500 µg/0.1 mL IVD and 26 eyes received 1.25 mg IVB. After 6 months of follow-up, the results indicated that visual acuity was significantly improved from 0.50 ± 0.13 in IVB and 0.52 ± 0.12 LogMAR in IVD at baseline to 0.2 ± 0.1 and 0.29 ± 0.07, respectively. Central macular thickness (CMT) and macular volume were measured based on spectral-domain optical coherence tomography (OCT) at month 1, 3, and 6. Both groups showed a significant reduction in CMT and macular volume from baseline but there was no significant difference between the IVB and IVD groups. Interestingly, IVD, but not IVB, decreased intraocular pressure (IOP), which is a desirable effect. There was no serious complication due to injections. This study sheds light into the long-term effects of NSAIDs and may support the idea that inflammation suppression by NSAIDs may have the same results as anti-VEGF administration.

Effects of multiple intravitreal anti-VEGF injections on retinal nerve fiber layer and intraocular pressure: a comparative clinical study

PubMed Central

Sobacı, Güngör; Güngör, Rıza; Özge, Gökhan

2013-01-01

AIM To determine the effect of multiple injections of ranibizumab or bevacizumab on retinal nerve fiber layer (RNFL) and intraocular pressure (IOP) in patients with age-related macular degeneration (AMD). METHODS This retrospective study includes 35 eyes of 35 patients treated with intravitreal bevacizumab (IVB, 1.25mg/0.05mL) and 30 eyes of 30 patients with intravitreal ranibizumab (IVR, 0.5mg/0.05mL) who had Fast RNFL analysis (Stratus™); IOP measurements were taken 30 minutes and 24 hours after each injection. RESULTS The mean ages were 68.0±7.5 and 69.1±7.7 years in the IVR and IVB groups, respectively (P=0.55). They underwent (6.3±1.9) and (5.1±1.3) injections (P=0.07) over (13.6±2.1) and (14.05±2.6) months (P=0.45) in the IVR and IVB groups, respectively. Changes in overall and temporal RNFL thickness in IVR-treated eyes (105.3±6.9µm and 74.4±11.2µm) were not different from those in untreated eyes in the IVR group (104.6± 8.4µm and 75.1±12.6µm) (P=0.57 and P=0.41, respectively). Similarly, overall and temporal RNFL thickness in IVB-treated eyes (105.8±8.1µm and 74.5±11.8µm) were not different from those in untreated eyes in the IVB group (104.6±8µm and 74.8±12.9µm) (P=0.42 and P=0.80, respectively). The frequencies of IOP rise (P=0.60) and changes in RNFL thickness from baseline (P=0.16) were comparable between groups. CONCLUSION Repeated intravitreal injection of ranibizumab or bevacizumab does not seem have adverse effects on RNFL thickness or IOP in wet AMD patients. PMID:23638426

Effects of multiple intravitreal anti-VEGF injections on retinal nerve fiber layer and intraocular pressure: a comparative clinical study.

PubMed

Sobacı, Güngör; Güngör, Rıza; Ozge, Gökhan

2013-01-01

To determine the effect of multiple injections of ranibizumab or bevacizumab on retinal nerve fiber layer (RNFL) and intraocular pressure (IOP) in patients with age-related macular degeneration (AMD). This retrospective study includes 35 eyes of 35 patients treated with intravitreal bevacizumab (IVB, 1.25mg/0.05mL) and 30 eyes of 30 patients with intravitreal ranibizumab (IVR, 0.5mg/0.05mL) who had Fast RNFL analysis (Stratus™); IOP measurements were taken 30 minutes and 24 hours after each injection. The mean ages were 68.0±7.5 and 69.1±7.7 years in the IVR and IVB groups, respectively (P=0.55). They underwent (6.3±1.9) and (5.1±1.3) injections (P=0.07) over (13.6±2.1) and (14.05±2.6) months (P=0.45) in the IVR and IVB groups, respectively. Changes in overall and temporal RNFL thickness in IVR-treated eyes (105.3±6.9µm and 74.4±11.2µm) were not different from those in untreated eyes in the IVR group (104.6± 8.4µm and 75.1±12.6µm) (P=0.57 and P=0.41, respectively). Similarly, overall and temporal RNFL thickness in IVB-treated eyes (105.8±8.1µm and 74.5±11.8µm) were not different from those in untreated eyes in the IVB group (104.6±8µm and 74.8±12.9µm) (P=0.42 and P=0.80, respectively). The frequencies of IOP rise (P=0.60) and changes in RNFL thickness from baseline (P=0.16) were comparable between groups. Repeated intravitreal injection of ranibizumab or bevacizumab does not seem have adverse effects on RNFL thickness or IOP in wet AMD patients.

Saturn Apollo Program

NASA Image and Video Library

1968-01-01

This view depicts engineers conducting a system test on the Saturn V instrument unit (IU) at International Business Machines (IBM) in Huntsville, Alabama. IBM is a prime contractor for development and fabrication of the IU. The IU is vital to the proper flight of the vehicle. It contains navigation, guidance, control, and sequencing equipment for the launch vehicle. Three-feet tall, twenty-one feet in diameter, and weighing about 4,000 pounds, the IU is mounted atop the S-IVB (third) stage, between the S-IVB stage and the Apollo spacecraft.

Saturn Apollo Program

NASA Image and Video Library

1967-02-18

This cutaway drawing shows the S-IVB (third stage) of the Saturn V launch vehicle. As a part of the Marshall Space Flight Center’s (MSFC) “building block” approach to the Saturn development, the S-IVB stage was utilized in the Saturn IB launch vehicle as a second stage and, later, the Saturn V launch vehicle as a third stage. The 59 foot long and 22 feet diameter stage was powered by a single J-2 engine, initially capable of 200,000 pounds of thrust.

Diverse C-Terminal Sequences Involved in Flavobacterium johnsoniae Protein Secretion

PubMed Central

Kulkarni, Surashree S.; Zhu, Yongtao; Brendel, Colton J.

2017-01-01

ABSTRACT Flavobacterium johnsoniae and many related bacteria secrete proteins across the outer membrane using the type IX secretion system (T9SS). Proteins secreted by T9SSs have amino-terminal signal peptides for export across the cytoplasmic membrane by the Sec system and carboxy-terminal domains (CTDs) targeting them for secretion across the outer membrane by the T9SS. Most but not all T9SS CTDs belong to the family TIGR04183 (type A CTDs). We functionally characterized diverse CTDs for secretion by the F. johnsoniae T9SS. Attachment of the CTDs from F. johnsoniae RemA, AmyB, and ChiA to the foreign superfolder green fluorescent protein (sfGFP) that had a signal peptide at the amino terminus resulted in secretion across the outer membrane. In each case, approximately 80 to 100 amino acids from the extreme carboxy termini were needed for efficient secretion. Several type A CTDs from distantly related members of the phylum Bacteroidetes functioned in F. johnsoniae, supporting the secretion of sfGFP by the F. johnsoniae T9SS. F. johnsoniae SprB requires the T9SS for secretion but lacks a type A CTD. It has a conserved C-terminal domain belonging to the family TIGR04131, which we refer to as a type B CTD. The CTD of SprB was required for its secretion, but attachment of C-terminal regions of SprB of up to 1,182 amino acids to sfGFP failed to result in secretion. Additional features outside the C-terminal region of SprB may be required for its secretion. IMPORTANCE Type IX protein secretion systems (T9SSs) are common in but limited to members of the phylum Bacteroidetes. Most proteins that are secreted by T9SSs have conserved carboxy-terminal domains that belong to the protein domain family TIGR04183 (type A CTDs) or TIGR04131 (type B CTDs). Here, we identify features of T9SS CTDs of F. johnsoniae that are required for protein secretion and demonstrate that type A CTDs from distantly related members of the phylum function with the F. johnsoniae T9SS to secrete the foreign protein sfGFP. In contrast, type B CTDs failed to target sfGFP for secretion, suggesting a more complex association with the T9SS. PMID:28396348

Acceptance and Commitment Therapy in Improving Well-Being in Patients With Stage III-IV Cancer and Their Partners

ClinicalTrials.gov

2018-02-06

Malignant Female Reproductive System Neoplasm; Malignant Hepatobiliary Neoplasm; Partner; Stage III Breast Cancer; Stage III Cervical Cancer; Stage III Colorectal Cancer; Stage III Lung Cancer; Stage III Prostate Cancer; Stage III Skin Melanoma; Stage III Uterine Corpus Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Lung Carcinoma; Stage IIIA Skin Melanoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Lung Carcinoma; Stage IIIB Skin Melanoma; Stage IIIB Uterine Corpus Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer; Stage IIIC Skin Melanoma; Stage IIIC Uterine Corpus Cancer; Stage IV Breast Cancer; Stage IV Cervical Cancer; Stage IV Colorectal Cancer; Stage IV Lung Cancer; Stage IV Prostate Cancer; Stage IV Skin Melanoma; Stage IV Uterine Corpus Cancer; Stage IVA Cervical Cancer; Stage IVA Colorectal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Cervical Cancer; Stage IVB Colorectal Cancer; Stage IVB Uterine Corpus Cancer

Carbide-forming groups IVB-VIB metals: a new territory in the periodic table for CVD growth of graphene.

PubMed

Zou, Zhiyu; Fu, Lei; Song, Xiuju; Zhang, Yanfeng; Liu, Zhongfan

2014-07-09

Early transition metals, especially groups IVB-VIB metals, can form stable carbides, which are known to exhibit excellent "noble-metal-like" catalytic activities. We demonstrate herein the applications of groups IVB-VIB metals in graphene growth using atmospheric pressure chemical vapor deposition technique. Similar to the extensively studied Cu, Ni, and noble metals, these transition-metal foils facilitate the catalytic growth of single- to few-layer graphene. The most attractive advantage over the existing catalysts is their perfect control of layer thickness and uniformity with highly flexible experimental conditions by in situ converting the dissolved carbons into stable carbides to fully suppress the upward segregation/precipitation effect. The growth performance of graphene on these transition metals can be well explained by the periodic physicochemical properties of elements. Our work has disclosed a new territory of catalysts in the periodic table for graphene growth and is expected to trigger more interest in graphene research.

Trametinib and TAS-102 in Treating Patients With Colon or Rectal Cancer That is Advanced, Metastatic, or Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-05-07

RAS Family Gene Mutation; Stage III Colon Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage III Rectal Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Colon Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IV Rectal Cancer AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7

Vitreous changes after intravitreal bevacizumab monotherapy for retinopathy of prematurity: a case series.

PubMed

Shoeibi, Nasser; Hosseini, Seyedeh Maryam; Banaee, Touka; Ansari-Astaneh, Mohammad-Reza; Abrishami, Majid; Ahmadieh, Hamid

2018-01-01

Reporting a special clinical finding after intravitreal bevacizumab monotherapy for retinopathy of prematurity. In a retrospective case series, the clinical courses of five premature infants with similar vitreous changes after a single dose of intravitreal bevacizumab (IVB) injection without additional laser therapy were reported. The mean post-conceptional age at IVB injection was 39.8 ± 2.2 (range 37-43) weeks. Localized vitreous syneresis and linear fibrotic vitreous condensation occurred 8.2 ± 2.3 weeks after IVB monotherapy in our patients (15.5% of injections). The mean last post injection visit was 61.6 ± 5.3 weeks (post-conceptional age). Further regression and complete retinal vascularization occurred in all patients. Thread-like vitreous condensation with localized vitreous liquefaction may be related to involutional ROP disease itself, combined to anti VEGF therapy and may be a predictor factor for further regression and retinal vascularization. The case series describes a successful response to anti-VEGF monotherapy with no further complications.

Regional and seasonal variations in facial sebum secretions: a proposal for the definition of combination skin type.

PubMed

Youn, Sang Woong; Na, Jung Im; Choi, Sun Young; Huh, Chang Hun; Park, Kyoung Chan

2005-08-01

Facial sebum secretions are known to change under various circumstances. Facial skin types have been categorized as oily, normal, dry, and combination types. However, these have been evaluated subjectively by individuals to date, and no objective accepted standard measurement method exists. The combination skin type is most common, but its definition is vaguer than the definitions of the other skin types. We measured facial sebum secretions with Sebumeter. Sebum secretions were measured at five sites of the face seasonally for a year, in the same volunteers. Using the data obtained we developed a set of rules to define the combination skin type. Regional differences in sebum secretion were confirmed. Sebum secretions on forehead, nose, and chin were higher than on both cheeks. Summer was found to be the highest sebum-secreting season, and seasonal variations were found in the T- and U-zones. A mismatch of skin type in the T- and U-zones in more than two seasons appears to be close to subjective ratings of what is described as the 'combination' skin type. We showed that the face shows definitive regional and seasonal variations in sebum secretion. To define the combination skin type, seasonal variations in sebum secretion should be considered in addition to regional variations.

Transoral Robotic Surgery in Treating Patients With Benign or Malignant Tumors of the Head and Neck

ClinicalTrials.gov

2018-06-26

Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage 0 Hypopharyngeal Cancer; Stage 0 Laryngeal Cancer; Stage 0 Lip and Oral Cavity Cancer; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Adenoid Cystic Carcinoma of the Oral Cavity; Stage II Mucoepidermoid Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Hypopharynx; Stage II Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Verrucous Carcinoma of the Larynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Cetuximab and Everolimus in Treating Patients With Metastatic or Recurrent Colon Cancer or Head and Neck Cancer

ClinicalTrials.gov

2012-07-06

Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Stage IVA Colon Cancer; Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Colon Cancer; Stage IVB Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVB Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVC Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Tongue Cancer

Long-Term Outcomes of Nasopharyngeal Carcinoma in 148 Children and Adolescents

PubMed Central

Lu, Suying; Chang, Hui; Sun, Xiaofei; Zhen, Zijun; Sun, Feifei; Zhu, Jia; Wang, Juan; Huang, Junting; Liao, Ru; Guo, Xiaofang; Lu, Lixia; Gao, Yuanhong

2016-01-01

Abstract The aim of this study was to investigate the survival and long-term morbidities of nasopharyngeal carcinoma (NPC) in children and adolescents. We retrospectively reviewed children and adolescents with NPC treated at Sun Yat-sen University Cancer Center from February 1991 to October 2010, where the prognostic factors and long-term effects of therapy were analyzed. A total of 148 patients were identified. The median age was 15 years old (range, 5–18 years) and the male to female ratio was 3.6:1. Most of the tumor histopathology was undifferentiated nonkeratinizing carcinoma (97.3%). The number of patients staged with IVa, IVb, IVc, III, and II were 45 (30.4%), 12 (8.1%), 5 (3.4%), 70 (47.3%), and 16 (10.8%), respectively. For the whole series with a median follow-up of 81 months (range, 6–282 months), the 5-year overall survival (OS) and disease-free survival (DFS) ratios were 79.3% and 69.7%, respectively. We observed significant differences in the 5-year OS (81.1% vs 25.0%, P = 0.002) and the DFS rates (72.2% vs 0.0%, P = 0.000) between patients with stage II to IVb disease and stage IVc disease. For patients with stage II, III, IVa, and IVb disease, we found a high radiation dose (dose > 66 Gy to the primary lesion) would not significantly improve the survival compared to the sub-high radiation dose group (dose = 60–66 Gy to the primary lesion), even considering the type of radiation therapy technologies. However, the incidences of sequelae (grades I–IV) in patients with high radiation dose were apparently higher than those in patients with low radiation dose. Considering the late sequelae, a dose of 60 to 66 Gy to the primary lesions seems to be enough for children and adolescents with NPC. PMID:27124036

Cosmic ray neutrino tests for heavier weak bosons and cosmic antimatter

NASA Technical Reports Server (NTRS)

Brown, R. W.; Stecker, F. W.

1981-01-01

A program for using high energy neutrino astronomy with large neutrino detectors to directly test for the existence of heavier weak intermediate vector bosons (ivb) and cosmic antimatter is described. Such observations can provide a direct test of baryon symmetric cosmologies. Changes in the total cross section for nu(N) yields mu(X) due to additional propagators are discussed and higher mass resonances in the annihilation channel bar-nu sub e e(-) yields X are analyzed. The annihilation channel is instrumental in the search for antimatter, partcularly if heavier IVB's exist.

Saturn Apollo Program

NASA Image and Video Library

1967-10-01

This is a view of the Saturn V instrument unit (IU) being manufactured in the east high bay at International Business Machines (IBM) in Huntsville, Alabama. IBM is a prime contractor for development and fabrication of the IU. The IU is vital to the proper flight of the vehicle. It contains navigation, guidance, control, and sequencing equipment for the launch vehicle. Three feet tall, twenty-one feet in diameter, and weighing about 4,000 pounds, the IU is mounted atop the S-IVB (third) stage, between the S-IVB stage and the Apollo spacecraft.

Wide angle view of Mission Control Center during Apollo 14 transmission

NASA Image and Video Library

1971-01-31

S71-17122 (31 Jan. 1971) --- A wide angle overall view of the Mission Operations Control Room (MOCR) in the Mission Control Center at the Manned spacecraft Center. This view was photographed during the first color television transmission from the Apollo 14 Command Module. Projected on the large screen at the right front of the MOCR is a view of the Apollo 14 Lunar Module, still attached to the Saturn IVB stage. The Command and Service Modules were approaching the LM/S-IVB during transposition and docking maneuvers.

Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer

ClinicalTrials.gov

2018-04-18

BRAF Gene Mutation; Poorly Differentiated Thyroid Gland Carcinoma; RAS Family Gene Mutation; Recurrent Thyroid Gland Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7

Phase I Study of Intravenous Triapine (IND # 68338) in Combination With Pelvic Radiation Therapy With or Without Weekly Intravenous Cisplatin Chemotherapy for Locally Advanced Cervical, Vaginal, or Pelvic Gynecologic Malignancies

ClinicalTrials.gov

2013-01-10

Recurrent Cervical Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Vaginal Cancer; Recurrent Vulvar Cancer; Stage III Vaginal Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Vulvar Cancer; Stage IV Ovarian Epithelial Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer

Olfactory Training in Improving Sense of Smell After Radiation Therapy in Patients With Paranasal Sinus or Nasopharyngeal Cancer

ClinicalTrials.gov

2017-07-11

Stage 0 Nasopharyngeal Carcinoma; Stage 0 Paranasal Sinus Cancer; Stage I Nasopharyngeal Carcinoma; Stage I Paranasal Sinus Cancer; Stage II Nasopharyngeal Carcinoma; Stage II Paranasal Sinus Cancer; Stage IIA Nasopharyngeal Carcinoma; Stage IIB Nasopharyngeal Carcinoma; Stage III Nasopharyngeal Carcinoma; Stage III Paranasal Sinus Cancer; Stage IV Nasopharyngeal Carcinoma; Stage IV Paranasal Sinus Cancer; Stage IVA Nasopharyngeal Carcinoma; Stage IVA Paranasal Sinus Cancer; Stage IVB Nasopharyngeal Carcinoma; Stage IVB Paranasal Sinus Cancer; Stage IVC Nasopharyngeal Carcinoma; Stage IVC Paranasal Sinus Cancer

Saturn Apollo Program

NASA Image and Video Library

1960-01-01

This image illustrates the basic differences between the three Saturn launch vehicles developed by the Marshall Space Flight Center. The Saturn I, consisted of two stages, the S-I (eight H-1 engines) and the S-IV (six RL-10 engines). The Saturn IB (center) also consisted of two stages, the S-IB (eight H-1 engines) and the S-IVB (one J-2 engine). The Saturn V consisted of three stages, the S-IC (five F-1 engines), the S-II (five J-2 engines), and the S-IVB (one J-2 engine).

Akt Inhibitor MK2206 in Treating Patients With Progressive, Recurrent, or Metastatic Adenoid Cyst Carcinoma

ClinicalTrials.gov

2018-03-21

Recurrent Oral Cavity Adenoid Cystic Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Adenoid Cystic Carcinoma; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7

Mars Technology Program: Planetary Protection Technology Development

NASA Technical Reports Server (NTRS)

Lin, Ying

2006-01-01

This slide presentation reviews the development of Planetary Protection Technology in the Mars Technology Program. The goal of the program is to develop technologies that will enable NASA to build, launch, and operate a mission that has subsystems with different Planetary Protection (PP) classifications, specifically for operating a Category IVb-equivalent subsystem from a Category IVa platform. The IVa category of planetary protection requires bioburden reduction (i.e., no sterilization is required) The IVb category in addition to IVa requirements: (i.e., terminal sterilization of spacecraft is required). The differences between the categories are further reviewed.

Saturn Apollo Program

NASA Image and Video Library

1966-02-01

AS-201, the first Saturn IB launch vehicle developed by the Marshall Space Flight Center (MSFC), lifts off from Cape Canaveral, Florida, February 26, 1966. This was the first flight of the S-IB and S-IVB stages, including the first flight test of the liquid-hydrogen/liquid oxygen-propelled J-2 engine in the S-IVB stage. During the thirty-seven minute flight, the vehicle reached an altitude of 303 miles and traveled 5,264 miles downrange. In all, nine Saturn IB flights were made, ending with the Apollo Soyuz Test Project (ASTP) in July 1975.

Bacterial Translocation Ratchets: Shared Physical Principles with Different Molecular Implementations: How bacterial secretion systems bias Brownian motion for efficient translocation of macromolecules.

PubMed

Hepp, Christof; Maier, Berenike

2017-10-01

Secretion systems enable bacteria to import and secrete large macromolecules including DNA and proteins. While most components of these systems have been identified, the molecular mechanisms of macromolecular transport remain poorly understood. Recent findings suggest that various bacterial secretion systems make use of the translocation ratchet mechanism for transporting polymers across the cell envelope. Translocation ratchets are powered by chemical potential differences generated by concentration gradients of ions or molecules that are specific to the respective secretion systems. Bacteria employ these potential differences for biasing Brownian motion of the macromolecules within the conduits of the secretion systems. Candidates for this mechanism include DNA import by the type II secretion/type IV pilus system, DNA export by the type IV secretion system, and protein export by the type I secretion system. Here, we propose that these three secretion systems employ different molecular implementations of the translocation ratchet mechanism. © 2017 The Authors. BioEssays Published by WILEY Periodicals, Inc.

Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

ClinicalTrials.gov

2017-09-26

Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

Combined treatment for Coats’ disease: retinal laser photocoagulation combined with intravitreal bevacizumab injection was effective in two cases

PubMed Central

2014-01-01

Background The exact pathogenetic mechanisms of Coats’ disease remain unknown. In this report, we show two cases of Coats’ disease that achieved a favorable prognosis with the combined treatment of intravitreal bevacizumab (IVB) injection prior to photocoagulation, although both initially resisted photocoagulation therapy. Case presentations Case 1 was a 15-year-old boy with initial visual acuity of 0.4 OD. At the temporal retina, aneurysms and abnormal telangiectatic vessels were observed. Hard exudates and an exudative retinal detachment extended to the fovea. He was diagnosed as having Coats’ disease at stage 3A and we performed laser photocoagulation as an initial approach to treat peripheral aneurysms and telangiectatic vessels. After the treatment, the exudative retinal detachment was eased and visual acuity improved to 1.0; however, recurrence occurred after 5 months. The exudative change was resistant against laser photocoagulation therapy and we therefore added IVB as an adjuvant before photocoagulation. Fourteen days after IVB injection phased laser photocoagulation was given to cover the abnormal capillaries, aneurysms and the leakage area spotted in FA. A good prognosis was obtained with decreased exudation and improved visual acuity. Case 2 was an 11-year-old boy with decreased visual acuity of 0.15 OS at the initial visit. Hard exudates, retinal edema and serous retinal detachment were seen at the macula and peripheral retina. Fluorescein angiography revealed telangiectatic capillaries at the temporal retina. Our diagnosis was Coats’ disease at stage 3A. Extensive photocoagulation was performed as an initial treatment to the lesion. However, the exudative change was severe and resistant against the photocoagulation treatment. Therefore, we added IVB as an adjuvant before photocoagulation. Exudative change in the retina seemed to be eased 7 days after IVB injection, therefore, phased laser phototherapy was added to cover the abnormal capillaries. After the combination therapy, exudative change was remarkably ameliorated and better visual acuity was achieved. Conclusion Bevacizumab is considered an effective adjuvant for Coats’ disease with exudative change resistant to retinal photocoagulation therapy. PMID:24666524

Detection of viral hemorrhagic septicemia virus

USGS Publications Warehouse

Winton, James; Kurath, Gael; Batts, William

2007-01-01

Viral hemorrhagic septicemia virus (VHSV) is considered to be one of the most important viral pathogens of finfish and is listed as reportable by many nations and international organizations (Office International des Epizooties 2006). Prior to 1988, VHSV was thought to be limited to Europe (Wolf 1988; Smail 1999). Subsequently, it was shown that the virus is endemic among many marine and anadromous fish species in both the Pacific and Atlantic Oceans (Meyers and Winton 1995; Skall et al. 2005). Genetic analysis reveals that isolates of VHSV can be divided into four genotypes that generally correlate with geographic location with the North American isolates generally falling into VHSV Genotype IV (Snow et al. 2004). In 2005-2006, reports from the Great Lakes region indicated that wild fish had experienced disease or, in some cases, very large die-offs from VHSV (Elsayed et al. 2006, Lumsden et al. 2007). The new strain from the Great Lakes, now identified as VHSV Genotype IVb, appears most closely related to isolates of VHSV from mortalities that occurred during 2000-2004 in rivers and near-shore areas of New Brunswick and Nova Scotia, Canada (Gagne et al. 2007). The type IVb isolate found in the Great Lakes region is the only strain outside of Europe that has been associated with significant mortality in freshwater species.

Development of a walleye spleen stromal cell line sensitive to viral hemorrhagic septicemia virus (VHSV IVb) and to protection by synthetic dsRNA.

PubMed

Vo, Nguyen T K; Bender, Aaron W; Ammendolia, Dustin A; Lumsden, John S; Dixon, Brian; Bols, Niels C

2015-07-01

A cell line, WE-spleen6, has been developed from the stromal layer of primary spleen cell cultures. On conventional plastic, WE-spleen6 cells had a spindle-shaped morphology at low cell density but grew to become epithelial-like at confluency. On the commercial extracellular matrix (ECM), Matrigel, the cells remained spindle-shaped and formed lumen-like structures. WE-spleen6 cells had intermediate filament protein, vimentin and the ECM protein, collagen I, but not smooth muscle α-actin (SMA) and von Willebrand factor (vWF) and lacked alkaline phosphatase and phagocytic activities. WE-spleen6 was more susceptible to infection with VHSV IVb than a fibroblast and epithelial cell lines from the walleye caudal fin, WE-cfin11f and WE-cfin11e, respectively. Viral transcripts and proteins appeared earlier in WE-spleen6 cultures as did cytopathic effect (CPE) and significant virus production. The synthetic double-stranded RNA (dsRNA), polyinosinic: polycytidylic acid (pIC), induced the antiviral protein Mx in both cell lines. Treating WE-spleen6 cultures with pIC prior to infection with VHSV IVb inhibited the early accumulation of viral transcripts and proteins and delayed the appearance of CPE and significant viral production. Of particular note, pIC caused the disappearance of viral P protein 2 days post infection. WE-spleen6 should be useful for investigating the impact of VHSV IVb on hematopoietic organs and the actions of pIC on the rhabdovirus life cycle. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparative susceptibility among three stocks of yellow perch, Perca flavescens (Mitchill), to viral haemorrhagic septicaemia virus strain IVb from the Great Lakes

USGS Publications Warehouse

Olson, W.; Emmenegger, E.; Glenn, J.; Winton, J.; Goetz, F.

2013-01-01

The Great Lakes strain of viral haemorrhagic septicaemia virus IVb (VHSV-IVb) is capable of infecting a wide number of naive species and has been associated with large fish kills in the Midwestern United States since its discovery in 2005. The yellow perch, Perca flavescens (Mitchill), a freshwater species commonly found throughout inland waters of the United States and prized for its high value in sport and commercial fisheries, is a species documented in several fish kills affiliated with VHS. In the present study, differences in survival after infection with VHSV IVb were observed among juvenile fish from three yellow perch broodstocks that were originally derived from distinct wild populations, suggesting innate differences in susceptibility due to genetic variance. While all three stocks were susceptible upon waterborne exposure to VHS virus infection, fish derived from the Midwest (Lake Winnebago, WI) showed significantly lower cumulative % survival compared with two perch stocks derived from the East Coast (Perquimans River, NC and Choptank River, MD) of the United States. However, despite differences in apparent susceptibility, clinical signs did not vary between stocks and included moderate-to-severe haemorrhages at the pelvic and pectoral fin bases and exophthalmia. After the 28-day challenge was complete, VHS virus was analysed in subsets of whole fish that had either survived or succumbed to the infection using both plaque assay and quantitative PCR methodologies. A direct correlation was identified between the two methods, suggesting the potential for both methods to be used to detect virus in a research setting.

The type III secretion system is involved in Escherichia coli K1 interactions with Acanthamoeba.

PubMed

Siddiqui, Ruqaiyyah; Malik, Huma; Sagheer, Mehwish; Jung, Suk-Yul; Khan, Naveed Ahmed

2011-08-01

The type III secretion system among Gram-negative bacteria is known to deliver effectors into host cell to interfere with host cellular processes. The type III secretion system in Yersina, Pseudomonas and Enterohemorrhagic Escherichia coli have been well documented to be involved in the bacterial pathogenicity. The existence of type III secretion system has been demonstrated in neuropathogenic E. coli K1 strains. Here, it is observed that the deletion mutant of type III secretion system in E. coli strain EC10 exhibited defects in the invasion and intracellular survival in Acanthamoeba castellanii (a keratitis isolate) compared to its parent strain. Next, it was determined whether type III secretion system plays a role in E. coli K1 survival inside Acanthamoeba during the encystment process. Using encystment assays, our findings revealed that the type III secretion system-deletion mutant exhibited significantly reduced survival inside Acanthamoeba cysts compared with its parent strain, EC10 (P<0.01). This is the first demonstration that the type III secretion system plays an important role in E. coli interactions with Acanthamoeba. A complete understanding of how amoebae harbor bacterial pathogens will help design strategies against E. coli transmission to the susceptible hosts. Copyright © 2011 Elsevier Inc. All rights reserved.

Palliative Radiotherapy in the Local Management of Stage IVB Esophageal Cancer: Factors Affecting Swallowing and Survival.

PubMed

Suzuki, Gen; Yamazaki, Hideya; Aibe, Norihiro; Masui, Koji; Tatekawa, Kotoha; Sasaki, Naomi; Kimoto, Takuya; Nishimura, Takeshi; Nakashima, Akihiro; Takenaka, Tadashi; Fujiwara, Hitoshi; Ishikawa, Takeshi; Yamada, Kei

2017-06-01

To clarify the role of external-beam radiotherapy in the local management of state IVB esophageal cancer. We reviewed records of 31 patients with histopathologically-proven squamous cell carcinoma who underwent radiotherapy for their primary lesion. The change in dysphagia score from before to after treatment was assessed. Nutritional support-free survival (NSFS) was also evaluated. The median overall survival was 6 months. The overall rate of improvement in dysphagia score was 73% (23/31). The median NSFS was 5 months. Age at presentation <67 years, tumor location in the middle thoracic esophagus, and tumor length <7 cm were associated with significant improvement in swallowing scores. Responders to radiotherapy had significantly longer NSFS than non-responders (p=0.04). Palliative radiotherapy in the local management of stage IVB esophageal cancer is an effective treatment option for dysphagia. Factors highly associated with improvement of swallowing are age, tumor location, and tumor length. Response to radiotherapy is the most important factor in improving NSFS. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Genotype-guided Dosing of mFOLFIRINOX Chemotherapy in Patients With Previously Untreated Advanced Gastrointestinal Malignancies

ClinicalTrials.gov

2018-03-08

Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adenocarcinoma of Unknown Primary; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Duct Cell Adenocarcinoma of the Pancreas; Intestinal Adenocarcinoma of the Stomach; Localized Unresectable Adult Primary Liver Cancer; Metastatic Carcinoma of Unknown Primary; Metastatic Extrahepatic Bile Duct Cancer; Mixed Adenocarcinoma of the Stomach; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Newly Diagnosed Carcinoma of Unknown Primary; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Gallbladder Cancer; Stage IIIA Gastric Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Gallbladder Cancer; Stage IIIB Gastric Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Rectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Gallbladder Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Gallbladder Cancer; Stage IVB Rectal Cancer; Unresectable Extrahepatic Bile Duct Cancer

Freeze-Dried Black Raspberries in Preventing Oral Cancer Recurrence in High-Risk Appalachian Patients Previously Treated With Surgery For Oral Cancer

ClinicalTrials.gov

2018-03-04

Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Flexitouch® Home Maintenance Therapy or Standard Home Maintenance Therapy in Treating Patients With Lower-Extremity Lymphedema Caused by Treatment for Cervical Cancer, Vulvar Cancer, or Endometrial Cancer

ClinicalTrials.gov

2014-12-29

Lymphedema; Stage 0 Cervical Cancer; Stage 0 Uterine Corpus Cancer; Stage 0 Vulvar Cancer; Stage I Uterine Corpus Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Uterine Corpus Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vulvar Cancer; Stage IV Uterine Corpus Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Stage IVB Vulvar Cancer

Publication search and retrieval system

USGS Publications Warehouse

Winget, Elizabeth A.

1981-01-01

The publication search and retrieval system of the Branch of Atlantic-Gulf of Mexico Geology, U.S. Geological Survey, Woods Hole, Mass., is a procedure for listing and describing branch-sponsored publications. It is designed for maintenance and retrieval by those having limited knowledge of computer languages and programs. Because this branch currently utilizes the Hewlett-Packard HP-1000 computer with RTE-IVB operating system, database entry and maintenance is performed in accordance with the TE-IVB Terminal User’s Reference Manual (Hewlett-Packard Company, 1980) and within the constraints of GRASP (Bowen and Botbol, 1975) and WOLF (Evenden, 1978).

Saturn Apollo Program

NASA Image and Video Library

1967-09-09

This image depicts the test firing of a J-2 engine in the S-IVB Test Stand at the Marshall Space Flight Center (MSFC). The J-2, developed by Rocketdyne under the direction of MSFC, was propelled by liquid hydrogen and liquid oxygen. A single J-2 was utilized in the S-IVB stage (the second stage for the Saturn IB and third stage for the Saturn V) and in a cluster of five for the second stage (S-II) of the Saturn V. Initially rated at 200,000 pounds of thrust, the engine was later upgraded in the Saturn V program to 230,000 pounds.

Design, fracture control, fabrication, and testing of pressurized space-vehicle structures

NASA Technical Reports Server (NTRS)

Babel, H. W.; Christensen, R. H.; Dixon, H. H.

1974-01-01

The relationship between analysis, design, fabrication, and testing of thin shells is illustrated by Saturn S-IVB, Thor, Delta, and other single-use and reusable large-size cryogenic aluminum tankage. The analyses and design to meet the design requirements are reviewed and include consideration of fracture control, general instability, and other failure modes. The effect of research and development testing on the structure is indicated. It is shown how fabrication and nondestructive and acceptance testing constrain the design. Finally, qualification testing is reviewed to illustrate the extent of testing used to develop the Saturn S-IVB.

Interlaminar and lateral excitatory amino acid connections in the striate cortex of monkey.

PubMed

Kisvarday, Z F; Cowey, A; Smith, A D; Somogyi, P

1989-02-01

The intrinsic excitatory amino acid pathways within the striate cortex of monkeys were studied by autoradiographic detection of retrogradely labeled somata following microinjections of D-3H-aspartate (D-3H-Asp) into different layers. The labeled amino acid was selectively accumulated by subpopulations of neurons and, to a small extent, by glial cells, the latter mainly in the supragranular layers. Immunocytochemical detection of neurons containing GABA showed that, apart from a few cells exclusively in layer I, GABAergic neurons do not accumulate D-3H-Asp. Several lines of evidence suggest that D-3H-Asp uptake occurred only at nerve terminals; thus, the pattern of perikaryal labeling allowed the delineation of interlaminar and lateral projections. Neurons in layer I probably project laterally, and layer I receives wide-ranging projections from layer IVB and layer V from cells up to 1300 microns laterally. Some neurons in layer II send a focused projection to lower layer VI. Some neurons in layers II/III project up to 1 mm laterally within their own layer, but relatively few neurons can be labeled in these projections. Similarly, in layers II/III few neurons can be retrogradely labeled from layers V and upper VI, and this projection is organized such that cells closer to the pia project deeper in layer V/VI. The connections of layer IVA could not be revealed separately because of the difficulty of confining injections to this thin sublamina. Neurons in layer IVB project up to 1300 microns within IVB itself. A small number of cells from IVB also project to layers III, IVC-alpha, V, and VI with much more restricted lateral spread. Neurons in upper IVC-alpha send axons to layer IVB with at least 600-800 microns lateral spread. Neurons in lower IVC-alpha/upper IVC-beta project to layer III with at least 300-500 microns lateral spread. The bottom 50-80 microns of layer IVC-beta contains neurons with a very focused projection, apparently exclusively to the layer III/IVA border region. Both layers IVC alpha and beta have rich connections within themselves, the beta sublayer having more restricted lateral connections. Some neurons in layer IVC-beta give a laterally restricted small input to layers IVC-alpha and IVB. Both IVC-alpha and -beta project to layers V and VI, and these projections are spread at least 400 microns laterally. Neurons in layer V project to all layers, but the projection to layers I-III and within layer V itself spread much further laterally than the projections to layers IV and VI.(ABSTRACT TRUNCATED AT 400 WORDS)

Type-IVC Secretion System: A Novel Subclass of Type IV Secretion System (T4SS) Common Existing in Gram-Positive Genus Streptococcus

PubMed Central

Chen, Chen; Gao, George F.

2012-01-01

A growing number of pathogens are being found to possess specialized secretion systems which they use in various ways to subvert host defenses. Type IV secretion system (T4SS) is one of versatile secretion systems essential for the virulence and even survival of some bacteria species, and they enable the secretion of protein and DNA substrates across the cell envelope. T4SS was once believed to be present only in Gram-negative bacteria. In this study, we present evidence of a new subclass of T4SS, Type-IVC secretion system and indicate its common existence in the Gram-positive bacterial genus Streptococcus. We further identified that VirB1, VirB4, VirB6 and VirD4 are the minimal key components of this system. Using genome comparisons and evolutionary relationship analysis, we proposed that Type-IVC secretion system is movable via transposon factors and mediates the conjugative transfer of DNA, enhances bacterial pathogenicity, and could cause large-scale outbreaks of infections in humans. PMID:23056296

CDC/1000: a Control Data Corporation remote batch terminal emulator for Hewlett-Packard minicomputers

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

Berg, D.E.

1981-02-01

The Control Data Corporation Type 200 User Terminal utilizes a unique communications protocol to provide users with batch mode remote terminal access to Control Data computers. CDC/1000 is a software subsystem that implements this protocol on Hewlett-Packard minicomputers running the Real Time Executive III, IV, or IVB operating systems. This report provides brief descriptions of the various software modules comprising CDC/1000, and contains detailed instructions for integrating CDC/1000 into the Hewlett Packard operating system and for operating UTERM, the user interface program for CDC/1000. 6 figures.

Vaginal microbiota and sexually transmitted infections that may influence transmission of cell-associated HIV.

PubMed

Cone, Richard A

2014-12-15

Vaginal microbiota and sexually transmitted infections (STIs) are likely to influence the transmission of cell-associated human immunodeficiency virus (HIV). Lactic acid produced by Lactobacillus-dominated microbiota (Nugent score 0-3) will likely inhibit transmission, especially female-to-male transmission. In contrast, polymicrobial microbiota (Nugent score 4-10), community state types IV-A and IV-B, and STIs will likely increase transmission of cell-associated HIV. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Computational prediction of secretion systems and secretomes of Brucella: identification of novel type IV effectors and their interaction with the host.

PubMed

Sankarasubramanian, Jagadesan; Vishnu, Udayakumar S; Dinakaran, Vasudevan; Sridhar, Jayavel; Gunasekaran, Paramasamy; Rajendhran, Jeyaprakash

2016-01-01

Brucella spp. are facultative intracellular pathogens that cause brucellosis in various mammals including humans. Brucella survive inside the host cells by forming vacuoles and subverting host defence systems. This study was aimed to predict the secretion systems and the secretomes of Brucella spp. from 39 complete genome sequences available in the databases. Furthermore, an attempt was made to identify the type IV secretion effectors and their interactions with host proteins. We predicted the secretion systems of Brucella by the KEGG pathway and SecReT4. Brucella secretomes and type IV effectors (T4SEs) were predicted through genome-wide screening using JVirGel and S4TE, respectively. Protein-protein interactions of Brucella T4SEs with their hosts were analyzed by HPIDB 2.0. Genes coding for Sec and Tat pathways of secretion and type I (T1SS), type IV (T4SS) and type V (T5SS) secretion systems were identified and they are conserved in all the species of Brucella. In addition to the well-known VirB operon coding for the type IV secretion system (T4SS), we have identified the presence of additional genes showing homology with T4SS of other organisms. On the whole, 10.26 to 14.94% of total proteomes were found to be either secreted (secretome) or membrane associated (membrane proteome). Approximately, 1.7 to 3.0% of total proteomes were identified as type IV secretion effectors (T4SEs). Prediction of protein-protein interactions showed 29 and 36 host-pathogen specific interactions between Bos taurus (cattle)-B. abortus and Ovis aries (sheep)-B. melitensis, respectively. Functional characterization of the predicted T4SEs and their interactions with their respective hosts may reveal the secrets of host specificity of Brucella.

Studying Coxiella burnetii Type IV Substrates in the Yeast Saccharomyces cerevisiae: Focus on Subcellular Localization and Protein Aggregation.

PubMed

Rodríguez-Escudero, María; Cid, Víctor J; Molina, María; Schulze-Luehrmann, Jan; Lührmann, Anja; Rodríguez-Escudero, Isabel

2016-01-01

Coxiella burnetii is a Gram-negative obligate parasitic bacterium that causes the disease Q-fever in humans. To establish its intracellular niche, it utilizes the Icm/Dot type IVB secretion system (T4BSS) to inject protein effectors into the host cell cytoplasm. The host targets of most cognate and candidate T4BSS-translocated effectors remain obscure. We used the yeast Saccharomyces cerevisiae as a model to express and study six C. burnetii effectors, namely AnkA, AnkB, AnkF, CBU0077, CaeA and CaeB, in search for clues about their role in C. burnetii virulence. When ectopically expressed in HeLa cells, these effectors displayed distinct subcellular localizations. Accordingly, GFP fusions of these proteins produced in yeast also decorated distinct compartments, and most of them altered cell growth. CaeA was ubiquitinated both in yeast and mammalian cells and, in S. cerevisiae, accumulated at juxtanuclear quality-control compartments (JUNQs) and insoluble protein deposits (IPODs), characteristic of aggregative or misfolded proteins. AnkA, which was not ubiquitinated, accumulated exclusively at the IPOD. CaeA, but not AnkA or the other effectors, caused oxidative damage in yeast. We discuss that CaeA and AnkA behavior in yeast may rather reflect misfolding than recognition of conserved targets in the heterologous system. In contrast, CBU0077 accumulated at vacuolar membranes and abnormal ER extensions, suggesting that it interferes with vesicular traffic, whereas AnkB associated with the yeast nucleolus. Both effectors shared common localization features in HeLa and yeast cells. Our results support the idea that C. burnetii T4BSS effectors manipulate multiple host cell targets, which can be conserved in higher and lower eukaryotic cells. However, the behavior of CaeA and AnkA prompt us to conclude that heterologous protein aggregation and proteostatic stress can be a limitation to be considered when using the yeast model to assess the function of bacterial effectors.

Studying Coxiella burnetii Type IV Substrates in the Yeast Saccharomyces cerevisiae: Focus on Subcellular Localization and Protein Aggregation

PubMed Central

Rodríguez-Escudero, María; Cid, Víctor J.; Molina, María; Schulze-Luehrmann, Jan; Lührmann, Anja; Rodríguez-Escudero, Isabel

2016-01-01

Coxiella burnetii is a Gram-negative obligate parasitic bacterium that causes the disease Q-fever in humans. To establish its intracellular niche, it utilizes the Icm/Dot type IVB secretion system (T4BSS) to inject protein effectors into the host cell cytoplasm. The host targets of most cognate and candidate T4BSS-translocated effectors remain obscure. We used the yeast Saccharomyces cerevisiae as a model to express and study six C. burnetii effectors, namely AnkA, AnkB, AnkF, CBU0077, CaeA and CaeB, in search for clues about their role in C. burnetii virulence. When ectopically expressed in HeLa cells, these effectors displayed distinct subcellular localizations. Accordingly, GFP fusions of these proteins produced in yeast also decorated distinct compartments, and most of them altered cell growth. CaeA was ubiquitinated both in yeast and mammalian cells and, in S. cerevisiae, accumulated at juxtanuclear quality-control compartments (JUNQs) and insoluble protein deposits (IPODs), characteristic of aggregative or misfolded proteins. AnkA, which was not ubiquitinated, accumulated exclusively at the IPOD. CaeA, but not AnkA or the other effectors, caused oxidative damage in yeast. We discuss that CaeA and AnkA behavior in yeast may rather reflect misfolding than recognition of conserved targets in the heterologous system. In contrast, CBU0077 accumulated at vacuolar membranes and abnormal ER extensions, suggesting that it interferes with vesicular traffic, whereas AnkB associated with the yeast nucleolus. Both effectors shared common localization features in HeLa and yeast cells. Our results support the idea that C. burnetii T4BSS effectors manipulate multiple host cell targets, which can be conserved in higher and lower eukaryotic cells. However, the behavior of CaeA and AnkA prompt us to conclude that heterologous protein aggregation and proteostatic stress can be a limitation to be considered when using the yeast model to assess the function of bacterial effectors. PMID:26821324

[Bile duct lesions in laparoscopic cholecystectomy].

PubMed

Siewert, J R; Ungeheuer, A; Feussner, H

1994-09-01

Laparoscopic cholecystectomy is both resulting in a slightly higher incidence of biliary lesions and a change of prevalence of the type of lesions. Damage to the biliary system occurs in 4 different types: The most severe case is the lesion with a structural defect of the hepatic or common bile duct with (IVa) or without (IVb) vascular injury. Tangential lesions without structural loss of the duct should be denominated as type III (IIIa with additional lesion to the vessels, type IIIb without). Type II comprehends late strictures without obvious intraoperative trauma to the duct. Type I includes immediate biliary fistulae of usually good prognosis. The increasing prevalence of structural defects of the bile ducts appears to be a peculiarity of laparoscopic cholecystectomy necessitating highly demanding operative repair. In the majority of cases, hepatico-jejunostomy or even intraparenchymatous anastomoses are required. Adaptation of well proven principles of open surgery is the best prevention of biliary lesions in laparoscopic cholecystectomy as well as the readiness to convert early to the open procedure.

Composite metal membrane

DOEpatents

Peachey, Nathaniel M.; Dye, Robert C.; Snow, Ronny C.; Birdsell, Stephan A.

1998-01-01

A composite metal membrane including a first metal layer of Group IVB met or Group VB metals, the first metal layer sandwiched between two layers of an oriented metal of palladium, platinum or alloys thereof is provided together with a process for the recovery of hydrogen from a gaseous mixture including contacting a hydrogen-containing gaseous mixture with a first side of a nonporous composite metal membrane including a first metal of Group IVB metals or Group VB metals, the first metal layer sandwiched between two layers of an oriented metal of palladium, platinum or alloys thereof, and, separating hydrogen from a second side of the nonporous composite metal membrane.

Composite metal membrane

DOEpatents

Peachey, N.M.; Dye, R.C.; Snow, R.C.; Birdsell, S.A.

1998-04-14

A composite metal membrane including a first metal layer of Group IVB met or Group VB metals, the first metal layer sandwiched between two layers of an oriented metal of palladium, platinum or alloys thereof is provided together with a process for the recovery of hydrogen from a gaseous mixture including contacting a hydrogen-containing gaseous mixture with a first side of a nonporous composite metal membrane including a first metal of Group IVB metals or Group VB metals, the first metal layer sandwiched between two layers of an oriented metal of palladium, platinum or alloys thereof, and, separating hydrogen from a second side of the nonporous composite metal membrane.

Stereotactic Radiosurgery Using CyberKnife in Treating Women With Advanced or Recurrent Gynecological Malignancies

ClinicalTrials.gov

2013-09-27

Fallopian Tube Cancer; Ovarian Sarcoma; Ovarian Stromal Cancer; Recurrent Cervical Cancer; Recurrent Endometrial Carcinoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Uterine Sarcoma; Recurrent Vaginal Cancer; Recurrent Vulvar Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Uterine Sarcoma; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IV Endometrial Carcinoma; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Uterine Sarcoma; Stage IV Vulvar Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer

Vorinostat in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma

ClinicalTrials.gov

2018-05-23

Recurrent Oral Cavity Adenoid Cystic Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Adenoid Cystic Carcinoma; Stage III Major Salivary Gland Cancer AJCC v7; Stage III Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Oral Cavity Adenoid Cystic Carcinoma AJCC v6 and v7; Tongue Carcinoma

Re-187 Os-187 Isotopic and Highly Siderophile Element Systematics of Group IVB Irons

NASA Technical Reports Server (NTRS)

Honesto, J.; McDonough, W. F.; Walker, R. J.; McCoy, T. J.; Ash, R. D.

2005-01-01

Study of the magmatic iron meteorite groups permits constraints to be placed on the chemical and isotopic composition of parent bodies, and the timing of, and crystal-liquid fractionation processes involved in the crystallization of asteroidal cores. Here we examine Re-Os isotopic and trace elemental systematics of group IVB irons. Compared to most irons, the irons comprising this group are enriched in some of the most refractory siderophile elements, yet highly-depleted in most volatile siderophile elements. These characteristics have been attributed to processes such as high temperature condensation of precursor materials and oxidation in the parent body. Most recently it has been suggested that both processes may be involved in the chemical complexity of the group. Here, high precision isotopic and highly siderophile element (HSE) concentrations are used to further examine these possible origins, and the crystallization history of the group. In addition, we have begun to assess the possibility of relating certain ungrouped irons with major groups via multi-element, trace element modeling. In a companion abstract, the isotopic and trace element systematics of the ungrouped iron Tishomingo are compared with the IVB irons.

Viral hemorrhagic septicemia virus (VHSV IVb) risk factors and association measures derived by expert panel

USGS Publications Warehouse

,

2010-01-01

Viral hemorrhagic septicemia virus (VHSV) is an OIE-listed pathogen of fish, recently expanding in known host and geographic range in North America. Through a group process designed for subjective probability assessment, an international panel of fish health experts identified and weighted risk factors perceived important to the emergence and spread of the viral genotype, VHSV IVb, within and from the Great Lakes region of the US and Canada. Identified factors included the presence of known VHSV-susceptible species, water temperatures conducive for disease, hydrologic connectivity and proximity to known VHSV-positive areas, untested shipments of live or frozen fish from known positive regions, insufficient regulatory infrastructure for fish health oversight, and uncontrolled exposure to fomites associated with boat and equipment or fish wastes from known VHSV-positive areas. Results provide qualitative insights for use in VHSV surveillance and risk-management planning, and quantitative estimates of contextual risk for use in a Bayesian model combining multiple evidence streams for joint probability assessment of disease freedom status. Consistency checks suggest that the compiled factors positively reflect expert judgment of watershed risk for acquiring VHSV IVb. External validation is recommended as the availability of empirical data permits.

Photodynamic Therapy With HPPH in Treating Patients With Squamous Cell Carcinoma of the Oral Cavity

ClinicalTrials.gov

2016-04-19

Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Oral Cavity

Computational and Experimental Analysis of the Secretome of Methylococcus capsulatus (Bath)

PubMed Central

Indrelid, Stine; Mathiesen, Geir; Jacobsen, Morten; Lea, Tor; Kleiveland, Charlotte R.

2014-01-01

The Gram-negative methanotroph Methylococcus capsulatus (Bath) was recently demonstrated to abrogate inflammation in a murine model of inflammatory bowel disease, suggesting interactions with cells involved in maintaining mucosal homeostasis and emphasizing the importance of understanding the many properties of M. capsulatus. Secreted proteins determine how bacteria may interact with their environment, and a comprehensive knowledge of such proteins is therefore vital to understand bacterial physiology and behavior. The aim of this study was to systematically analyze protein secretion in M. capsulatus (Bath) by identifying the secretion systems present and the respective secreted substrates. Computational analysis revealed that in addition to previously recognized type II secretion systems and a type VII secretion system, a type Vb (two-partner) secretion system and putative type I secretion systems are present in M. capsulatus (Bath). In silico analysis suggests that the diverse secretion systems in M.capsulatus transport proteins likely to be involved in adhesion, colonization, nutrient acquisition and homeostasis maintenance. Results of the computational analysis was verified and extended by an experimental approach showing that in addition an uncharacterized protein and putative moonlighting proteins are released to the medium during exponential growth of M. capsulatus (Bath). PMID:25479164

A Bacterial Pathogen uses Distinct Type III Secretion Systems to Alternate between Host Kingdom

USDA-ARS?s Scientific Manuscript database

Gram-negative bacterial pathogens of eukaryotes often secrete proteins directly into host cells via a needle-like protein channel called a ‘type III secretion system’ (T3SS). Bacteria that are adapted to either animal or plant hosts use phylogenetically distinct T3SSs for secreting proteins. Here, ...

Identification of genes encoding the type IX secretion system and secreted proteins in Flavobacterium columnare IA-S-4

USDA-ARS?s Scientific Manuscript database

Flavobacterium columnare, a member of the phylum Bacteroidetes, causes columnaris disease in wild and aquaculture-reared freshwater fish. The mechanisms responsible for columnaris disease are not known. Many members of the phylum Bacteroidetes use type IX secretion systems (T9SSs) to secrete enzymes...

Structure of the CFA/III major pilin subunit CofA from human enterotoxigenic Escherichia coli determined at 0.90 Å resolution by sulfur-SAD phasing.

PubMed

Fukakusa, Shunsuke; Kawahara, Kazuki; Nakamura, Shota; Iwashita, Takaki; Baba, Seiki; Nishimura, Mitsuhiro; Kobayashi, Yuji; Honda, Takeshi; Iida, Tetsuya; Taniguchi, Tooru; Ohkubo, Tadayasu

2012-10-01

CofA, a major pilin subunit of colonization factor antigen III (CFA/III), forms pili that mediate small-intestinal colonization by enterotoxigenic Escherichia coli (ETEC). In this study, the crystal structure of an N-terminally truncated version of CofA was determined by single-wavelength anomalous diffraction (SAD) phasing using five sulfurs in the protein. Given the counterbalance between anomalous signal strength and the undesired X-ray absorption of the solvent, diffraction data were collected at 1.5 Å resolution using synchrotron radiation. These data were sufficient to elucidate the sulfur substructure at 1.38 Å resolution. The low solvent content (29%) of the crystal necessitated that density modification be performed with an additional 0.9 Å resolution data set to reduce the phase error caused by the small sulfur anomalous signal. The CofA structure showed the αβ-fold typical of type IVb pilins and showed high structural homology to that of TcpA for toxin-coregulated pili of Vibrio cholerae, including spatial distribution of key residues critical for pilin self-assembly. A pilus-filament model of CofA was built by computational docking and molecular-dynamics simulation using the previously reported filament model of TcpA as a structural template. This model revealed that the CofA filament surface was highly negatively charged and that a 23-residue-long loop between the α1 and α2 helices filled the gap between the pilin subunits. These characteristics could provide a unique binding epitope for the CFA/III pili of ETEC compared with other type IVb pili.

bdhA-patD operon as a virulence determinant, revealed by a novel large-scale approach for identification of Legionella pneumophila mutants defective for amoeba infection.

PubMed

Aurass, P; Pless, B; Rydzewski, K; Holland, G; Bannert, N; Flieger, A

2009-07-01

Legionella pneumophila, the causative agent of Legionnaires' disease, is an intracellular parasite of eukaryotic cells. In the environment, it colonizes amoebae. After being inhaled into the human lung, the bacteria infect and damage alveolar cells in a way that is mechanistically similar to the amoeba infection. Several L. pneumophila traits, among those the Dot/Icm type IVB protein secretion machinery, are essential for exploiting host cells. In our search for novel Legionella virulence factors, we developed an agar plate assay, designated the scatter screen, which allowed screening for mutants deficient in infecting Acanthamoeba castellanii amoebae. Likewise, an L. pneumophila clone bank consisting of 23,000 transposon mutants was investigated here, and 19 different established Legionella virulence genes, for example, dot/icm genes, were identified. Importantly, 70 novel virulence-associated genes were found. One of those is L. pneumophila bdhA, coding for a protein with homology to established 3-hydroxybutyrate dehydrogenases involved in poly-3-hydroxybutyrate metabolism. Our study revealed that bdhA is cotranscribed with patD, encoding a patatin-like protein of L. pneumophila showing phospholipase A and lysophospholipase A activities. In addition to strongly reduced lipolytic activities and increased poly-3-hydroxybutyrate levels, the L. pneumophila bdhA-patD mutant showed a severe replication defect in amoebae and U937 macrophages. Our data suggest that the operon is involved in poly-3-hydroxybutyrate utilization and phospholipolysis and show that the bdhA-patD operon is a virulence determinant of L. pneumophila. In summary, the screen for amoeba-sensitive Legionella clones efficiently isolated mutants that do not grow in amoebae and, in the case of the bdhA-patD mutant, also human cells.

SigmaS controls multiple pathways associated with intracellular multiplication of Legionella pneumophila.

PubMed

Hovel-Miner, Galadriel; Pampou, Sergey; Faucher, Sebastien P; Clarke, Margaret; Morozova, Irina; Morozov, Pavel; Russo, James J; Shuman, Howard A; Kalachikov, Sergey

2009-04-01

Legionella pneumophila is the causative agent of the severe and potentially fatal pneumonia Legionnaires' disease. L. pneumophila is able to replicate within macrophages and protozoa by establishing a replicative compartment in a process that requires the Icm/Dot type IVB secretion system. The signals and regulatory pathways required for Legionella infection and intracellular replication are poorly understood. Mutation of the rpoS gene, which encodes sigma(S), does not affect growth in rich medium but severely decreases L. pneumophila intracellular multiplication within protozoan hosts. To gain insight into the intracellular multiplication defect of an rpoS mutant, we examined its pattern of gene expression during exponential and postexponential growth. We found that sigma(S) affects distinct groups of genes that contribute to Legionella intracellular multiplication. We demonstrate that rpoS mutants have a functional Icm/Dot system yet are defective for the expression of many genes encoding Icm/Dot-translocated substrates. We also show that sigma(S) affects the transcription of the cpxR and pmrA genes, which encode two-component response regulators that directly affect the transcription of Icm/Dot substrates. Our characterization of the L. pneumophila small RNA csrB homologs, rsmY and rsmZ, introduces a link between sigma(S) and the posttranscriptional regulator CsrA. We analyzed the network of sigma(S)-controlled genes by mutational analysis of transcriptional regulators affected by sigma(S). One of these, encoding the L. pneumophila arginine repressor homolog gene, argR, is required for maximal intracellular growth in amoebae. These data show that sigma(S) is a key regulator of multiple pathways required for L. pneumophila intracellular multiplication.

Alveolar type II cell-fibroblast interactions, synthesis and secretion of surfactant and type I collagen.

PubMed

Griffin, M; Bhandari, R; Hamilton, G; Chan, Y C; Powell, J T

1993-06-01

During alveolar development and alveolar repair close contacts are established between fibroblasts and lung epithelial cells through gaps in the basement membrane. Using co-culture systems we have investigated whether these close contacts influence synthesis and secretion of the principal surfactant apoprotein (SP-A) by cultured rat lung alveolar type II cells and the synthesis and secretion of type I collagen by fibroblasts. The alveolar type II cells remained cuboidal and grew in colonies on fibroblast feeder layers and on Matrigel-coated cell culture inserts but were progressively more flattened on fixed fibroblast monolayers and plastic. Alveolar type II cells cultured on plastic released almost all their SP-A into the medium by 4 days. Alveolar type II cells cultured on viable fibroblasts or Matrigel-coated inserts above fibroblasts accumulated SP-A in the medium at a constant rate for the first 4 days, and probably recycle SP-A by endocytosis. The amount of mRNA for SP-A was very low after 4 days of culture of alveolar type II cells on plastic, Matrigel-coated inserts or fixed fibroblast monolayers: relatively, the amount of mRNA for SP-A was increased 4-fold after culture of alveolar type II cells on viable fibroblasts. Co-culture of alveolar type II cells with confluent human dermal fibroblasts stimulated by 2- to 3-fold the secretion of collagen type I into the culture medium, even after the fibroblasts' growth had been arrested with mitomycin C. Collagen secretion, by fibroblasts, also was stimulated 2-fold by conditioned medium from alveolar type II cells cultured on Matrigel. The amount of mRNA for type I collagen increased only modestly when fibroblasts were cultured in this conditioned medium. This stimulation of type I collagen secretion diminished as the conditioned medium was diluted out, but at high dilutions further stimulation occurred, indicating that a factor that inhibited collagen secretion also was being diluted out. The conditioned medium contained low levels of IGF-1 and the stimulation of type I collagen secretion was abolished when the conditioned medium was pre-incubated with antibodies to insulin-like growth factor 1 (IGF-1). There are important reciprocal interactions between alveolar type II cells and fibroblasts in co-culture. Direct contacts between alveolar type II cells and fibroblasts appear to have a trophic effect on cultured alveolar type II cells, increasing the levels of mRNA for SP-A. Rat lung alveolar type II cells appear to release a factor (possibly IGF-1) that stimulates type I collagen secretion by fibroblasts.

Apollo 8 Mission Report

NASA Technical Reports Server (NTRS)

1969-01-01

Postflight analysis of Apollo 8 mission. Apollo 8 was the second manned flight in the program and the first manned lunar orbit mission. The crew were Frank Borman, Commander; James A. Lovell, Command Module Pilot; and William A. Anders, Lunar Module Pilot. The Apollo 8 space vehicle was launched on time from Kennedy Space Center, Florida, at 7:51:00 AM, EST, on December 21, 1968. Following a nominal boost phase, the spacecraft and S-IVB combination was inserted - into a parking orbit of 98 by 103 nautical miles. After a post-insertion checkout of spacecraft systems, the 319-second translunar injection maneuver was initiated at 2:50:37 by reignition of the S-IVB engine.

Romidepsin and Lenalidomide in Treating Patients With Previously Untreated Peripheral T-Cell Lymphoma

ClinicalTrials.gov

2018-01-05

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome

Distribution and diversity of bacterial secretion systems across metagenomic datasets.

PubMed

Barret, Matthieu; Egan, Frank; O'Gara, Fergal

2013-02-01

Bacteria can manipulate their surrounding environment through the secretion of proteins into other living organisms and into the extracellular milieu. In Gram stain negative bacteria this process is mediated by different types of secretion systems from type I through type VI secretion system (T1SS-T6SS). In this study the prevalence of these secretion systems in 312 publicly available microbiomes derived from a wide range of ecosystems was investigated by a gene-centric approach. Our analysis demonstrates that some secretion systems are over-represented in some specific samples. In addition, some T3SS and T6SS phylogenetic clusters were specifically enriched in particular ecological niches, which could indicate specific bacterial adaptation to these environments. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

Correlating levels of type III secretion and secreted proteins with fecal shedding of Escherichia coli O157:H7 in cattle

USDA-ARS?s Scientific Manuscript database

The locus of enterocyte effacement (LEE) encodes a type III secretion system (T3SS) for secreting factors that enable Escherichia coli O157:H7 to produce attaching and effacing lesions (A/E) on epithelial cells. The importance of LEE-encoded proteins in intestinal colonization of cattle is well-stud...

Crystal structure of the Yersinia type III secretion protein YscE

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

Phan, Jason; Austin, Brian P.; Waugh, David S.

2010-12-06

The plague-causing bacterium Yersinia pestis utilizes a contact-dependent (type III) secretion system (T3SS) to transport virulence factors from the bacterial cytosol directly into the interior of mammalian cells where they interfere with signal transduction pathways that mediate phagocytosis and the inflammatory response. The type III secretion apparatus is composed of 20-25 different Yersinia secretion (Ysc) proteins. We report here the structure of YscE, the smallest Ysc protein, which is a dimer in solution. The probable mode of oligomerization is discussed.

Comparison of grid laser, intravitreal triamcinolone, and intravitreal bevacizumab in the treatment of diffuse diabetic macular edema.

PubMed

Sobaci, Güngör; Ozge, Gökhan; Erdurman, Cüneyt; Durukan, Hakan A; Bayraktar, Zeki M

2012-01-01

To compare the effects of grid laser (GL), intravitreal bevacizumab (IVB), and intravitreal triamcinolone acetonide (IVTA) in diffuse diabetic macular edema (DDME). One hundred and twenty-six patients (126 eyes) treated with GL (modified grid), IVTA (4 mg), and IVB (1.25 mg) injections, matched for best corrected visual acuity (BCVA) and OCT-based central macular thickness at presentation, were enrolled. Primary outcome measure was change in best corrected logMAR visual acuity at 1-year follow-up. Rates of visual stabilization (within ±0.2 logMAR of baseline BCVA) (71.4, 83.3, 78.6%, respectively) were not different between the groups (p = 0.41) at 12-month follow-up. Higher rates of anatomical and functional success, however, were evident in IVB and IVTA groups within 6 months of treatment (p < 0.05 for both). No severe adverse effects except higher intraocular pressure (10 mm Hg from baseline) in one third (14 eyes) of the IVTA cases, who required trabeculectomy in 2 (4.8%) eyes, were observed. Intraocular injections may give favorable results within the first 6 months, and after 6 months, GL results seem to be more favorable in the treatment of treatment-naïve, acute, nonischemic, and center-involving DDME. Copyright © 2011 S. Karger AG, Basel.

Distribution and characterization of methicillin-resistant Staphylococcus aureus (MRSA) at the small animal hospital, faculty of veterinary medicine, Chiang Mai University, Thailand.

PubMed

Patchanee, Prapas; Tadee, Pakpoom; Ingkaninan, Pimlada; Tankaew, Pallop; Hoet, Armando E; Chupia, Vena

2014-03-01

Of 416 samples taken from veterinary staff (n = 30), dogs (n = 356) and various environmental sites (n = 30) at the Small Animal Hospital, Faculty of Veterinary Medicine, Chiang Mai University, Thailand, 13 samples contained methicillin-resistant Staphylococcus aureus (MRSA), of which 1 (SCCmec type II) came from veterinarian, 9 (SCCmec types I, III, IVa, V and untypeable) from dogs, and 3 (SCCmec types I, III, and IVb) from environmental samples. The MRSA isolates were 100% susceptible to vancomycin (100%), 69% to cephazolin and 62% to gentamicin, but were up to 92% resistant to tetracycline group, 69% to trimethoprim-sulfamethoxazoles and 62% to ceftriaxone. In addition, all MRSA isolates showed multidrug resistance. As the MRSA isolates from the veterinary staff and dogs were of different SCCmec types, this suggests there were no cross-infections. However, environmental contamination appears to have come from dogs, and appropriate hygienic practices should be introduced to solve this problem.

Engineering Escherichia coli into a protein delivery system for mammalian cells.

PubMed

Reeves, Analise Z; Spears, William E; Du, Juan; Tan, Kah Yong; Wagers, Amy J; Lesser, Cammie F

2015-05-15

Many Gram-negative pathogens encode type 3 secretion systems, sophisticated nanomachines that deliver proteins directly into the cytoplasm of mammalian cells. These systems present attractive opportunities for therapeutic protein delivery applications; however, their utility has been limited by their inherent pathogenicity. Here, we report the reengineering of a laboratory strain of Escherichia coli with a tunable type 3 secretion system that can efficiently deliver heterologous proteins into mammalian cells, thereby circumventing the need for virulence attenuation. We first introduced a 31 kB region of Shigella flexneri DNA that encodes all of the information needed to form the secretion nanomachine onto a plasmid that can be directly propagated within E. coli or integrated into the E. coli chromosome. To provide flexible control over type 3 secretion and protein delivery, we generated plasmids expressing master regulators of the type 3 system from either constitutive or inducible promoters. We then constructed a Gateway-compatible plasmid library of type 3 secretion sequences to enable rapid screening and identification of sequences that do not perturb function when fused to heterologous protein substrates and optimized their delivery into mammalian cells. Combining these elements, we found that coordinated expression of the type 3 secretion system and modified target protein substrates produces a nonpathogenic strain that expresses, secretes, and delivers heterologous proteins into mammalian cells. This reengineered system thus provides a highly flexible protein delivery platform with potential for future therapeutic applications.

Risk factors of recurrence of macular oedema associated with branch retinal vein occlusion after intravitreal bevacizumab injection.

PubMed

Yoo, Jun Ho; Ahn, Jaemoon; Oh, Jaeryung; Cha, Jaehyung; Kim, Seong-Woo

2017-10-01

To identify risk factors of recurrence of macular oedema in branch retinal vein occlusion (BRVO) after intravitreal bevacizumab (IVB) injection. The records of 63 patients who underwent IVB injection for macular oedema secondary to BRVO with at least 6 months of follow-up were reviewed. Patients were evaluated at baseline with fluorescein angiography (FA), optical coherence tomography (OCT) and ultra-wide-field fundus photography (WFP). During follow-up, OCT and WFP were repeated. The area of retinal haemorrhage, central retinal thickness (CRT), area (mm 2 ) of capillary non-perfusion within the 1 mm (NPA1), 1-3 mm and 6 mm zones of the ETDRS circle, foveal capillary filling time, degree (°) of foveal capillary network destruction and FA pattern were analysed. Macular oedema recurred in 41 of 63 (65.1%) eyes after initial IVB injection. A binary logistic regression model showed that NPA1 (OR=434.97; 95% CI=5.52 to 34262.12, p=0.006) and initial CRT (OR=1.004; 95% CI=1.000 to 1.008, p=0.015) were significantly associated with the recurrence of macular oedema. Receiver operating characteristic curve analysis identified an NPA1 of 0.36 mm 2 (AUC: 0.735, sensitivity: 70.7%; specificity: 63.6%) and an initial CRT of 570 µm (AUC: 0.745, sensitivity: 63.4%; specificity: 77.3%) as cut-off values for predicting recurrence of macular oedema. Patients with BRVO with non-perfusion of more than half of the 1 mm zone of the ETDRS circle or with an initial CRT >570 µm should be closely monitored for macular oedema recurrence within 6 months of IVB injection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems

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

Samudrala, Ram; Heffron, Fred; McDermott, Jason E.

2009-04-24

The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates, effector proteins, are not. We have used a machine learning approach to identify new secreted effectors. The method integrates evolutionary measures, such as the pattern of homologs in a range of other organisms, and sequence-based features, such as G+C content, amino acid composition and the N-terminal 30 residues of the protein sequence. The method was trained on known effectors from Salmonella typhimurium and validated on a corresponding set of effectors from Pseudomonas syringae, aftermore » eliminating effectors with detectable sequence similarity. The method was able to identify all of the known effectors in P. syringae with a specificity of 84% and sensitivity of 82%. The reciprocal validation, training on P. syringae and validating on S. typhimurium, gave similar results with a specificity of 86% when the sensitivity level was 87%. These results show that type III effectors in disparate organisms share common features. We found that maximal performance is attained by including an N-terminal sequence of only 30 residues, which agrees with previous studies indicating that this region contains the secretion signal. We then used the method to define the most important residues in this putative secretion signal. Finally, we present novel predictions of secreted effectors in S. typhimurium, some of which have been experimentally validated, and apply the method to predict secreted effectors in the genetically intractable human pathogen Chlamydia trachomatis. This approach is a novel and effective way to identify secreted effectors in a broad range of pathogenic bacteria for further experimental characterization and provides insight into the nature of the type III secretion signal.« less

A two-dimensional electrophoretic profile of the proteins secreted by Herbaspirillum seropedicae strain Z78.

PubMed

Chaves, Daniela Fojo Seixas; de Souza, Emanuel Maltempi; Monteiro, Rose Adele; de Oliveira Pedrosa, Fábio

2009-11-02

Herbaspirillum seropedicae is an endophytic bacterium that associates with rice, sugarcane and other economically important crops. Secreted proteins play a key role in the plant-bacterial interaction. Using 2D electrophoresis and peptide mass fingerprint mass spectrometry, 63 protein spots representing 41 different secreted proteins were identified during growth of H. seropedicae under nitrogen-sufficient conditions. In silico analysis showed that 25.4% of the proteins had signal peptides and 15.9% were predicted to be non-classically secreted. Among the most abundant were flagellar components and ABC-type transport system proteins. Nine secreted proteins had also been identified in the cellular proteome, suggesting that they also play a role in the extracellular environment. No type III secreted proteins were detected by comparison of the wild type strain with an hrcN mutant strain.

Analytical electron microscope study of eight ataxites

NASA Technical Reports Server (NTRS)

Novotny, P. M.; Goldstein, J. I.; Williams, D. B.

1982-01-01

Optical and electron optical (SEM, TEM, AEM) techniques were employed to investigate the fine structure of eight ataxite-iron meteorites. Structural studies indicated that the ataxites can be divided into two groups: a Widmanstaetten decomposition group and a martensite decomposition group. The Widmanstaetten decomposition group has a Type I plessite microstructure and the central taenite regions contain highly dislocated lath martensite. The steep M shaped Ni gradients in the taenite are consistent with the fast cooling rates, of not less than 500 C/my, observed for this group. The martensite decomposition group has a Type III plessite microstructure and contains all the chemical group IVB ataxites. The maximum taenite Ni contents vary from 47.5 to 52.7 wt % and are consistent with slow cooling to low temperatures of not greater than 350 C at cooling rates of not greater than 25 C/my.

The type IX secretion system is required for virulence of the fish pathogen Flavobacterium columnare

USDA-ARS?s Scientific Manuscript database

Flavobacterium columnare, a member of the phylum Bacteroidetes, causes columnaris disease in wild and aquaculture-reared freshwater fish. The mechanisms responsible for columnaris disease are not known. Many members of the phylum Bacteroidetes use type IX secretion systems (T9SSs) to secrete enzymes...

Pembrolizumab and Interferon Gamma-1b in Treating Patients With Stage IB-IVB Relapsed or Refractory Mycosis Fungoides and Sezary Syndrome

ClinicalTrials.gov

2018-06-08

Recurrent Mycosis Fungoides and Sezary Syndrome; Refractory Mycosis Fungoides; Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage II Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage III Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IV Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVB Mycosis Fungoides and Sezary Syndrome AJCC v7

Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations

ClinicalTrials.gov

2018-06-01

Advanced Malignant Neoplasm; Cervical Squamous Cell Carcinoma; Endometrial Carcinoma; Malignant Uterine Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Malignant Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage III Bladder Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Cancer; Stage IV Breast Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IVA Bladder Cancer; Stage IVA Cervical Cancer; Stage IVB Bladder Cancer; Stage IVB Cervical Cancer

Escherichia coli type III secretion system 2: a new kind of T3SS?

PubMed

Zhou, Mingxu; Guo, Zhiyan; Duan, Qiangde; Hardwidge, Philip R; Zhu, Guoqiang

2014-03-19

Type III secretion systems (T3SSs) are employed by Gram-negative bacteria to deliver effector proteins into the cytoplasm of infected host cells. Enteropathogenic Escherichia coli use a T3SS to deliver effector proteins that result in the creation of the attaching and effacing lesions. The genome sequence of the Escherichia coli pathotype O157:H7 revealed the existence of a gene cluster encoding components of a second type III secretion system, the E. coli type III secretion system 2 (ETT2). Researchers have revealed that, although ETT2 may not be a functional secretion system in most (or all) strains, it still plays an important role in bacterial virulence. This article summarizes current knowledge regarding the E. coli ETT2, including its genetic characteristics, prevalence, function, association with virulence, and prospects for future work.

Edwardsiella tarda EscE (Orf13 Protein) Is a Type III Secretion System-Secreted Protein That Is Required for the Injection of Effectors, Secretion of Translocators, and Pathogenesis in Fish.

PubMed

Lu, Jin Fang; Wang, Wei Na; Wang, Gai Ling; Zhang, He; Zhou, Ying; Gao, Zhi Peng; Nie, Pin; Xie, Hai Xia

2016-01-01

The type III secretion system (T3SS) of Edwardsiella tarda is crucial for its intracellular survival and pathogenesis in fish. The orf13 gene (escE) of E. tarda is located 84 nucleotides (nt) upstream of esrC in the T3SS gene cluster. We found that EscE is secreted and translocated in a T3SS-dependent manner and that amino acids 2 to 15 in the N terminus were required for a completely functional T3SS in E. tarda. Deletion of escE abolished the secretion of T3SS translocators, as well as the secretion and translocation of T3SS effectors, but did not influence their intracellular protein levels in E. tarda. Complementation of the escE mutant with a secretion-incompetent EscE derivative restored the secretion of translocators and effectors. Interestingly, the effectors that were secreted and translocated were positively correlated with the EscE protein level in E. tarda. The escE mutant was attenuated in the blue gourami fish infection model, as its 50% lethal dose (LD50) increased to 4 times that of the wild type. The survival rate of the escE mutant-strain-infected fish was 69%, which was much higher than that of the fish infected with the wild-type bacteria (6%). Overall, EscE represents a secreted T3SS regulator that controls effector injection and translocator secretion, thus contributing to E. tarda pathogenesis in fish. The homology of EscE within the T3SSs of other bacterial species suggests that the mechanism of secretion and translocation control used by E. tarda may be commonly used by other bacterial pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Salmonella-secreted Virulence Factors

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

Heffron, Fred; Niemann, George; Yoon, Hyunjin

In this short review we discuss secreted virulence factors of Salmonella, which directly affect Salmonella interaction with its host. Salmonella secretes protein to subvert host defenses but also, as discussed, to reduce virulence thereby permitting the bacteria to persist longer and more successfully disperse. The type III secretion system (TTSS) is the best known and well studied of the mechanisms that enable secretion from the bacterial cytoplasm to the host cell cytoplasm. Other secretion systems include outer membrane vesicles, which are present in all Gram-negative bacteria examined to date, two-partner secretion, and type VI secretion will also be addressed. Excellentmore » reviews of Salmonella secreted effectors have focused on themes such as actin rearrangements, vesicular trafficking, ubiquitination, and the activities of the virulence factors themselves. This short review is based on S. Typhimurium infection of mice because it is a model of typhoid like disease in humans. We have organized effectors in terms of events that happen during the infection cycle and how secreted effectors may be involved.« less

Molecular characterization of a functional type VI secretion system from a clinical isolate of Aeromonas hydrophila

EPA Science Inventory

Our laboratory recently molecularly characterized the type II secretion system (T2SS)-associated cytotoxic enterotoxin (Act) and the T3SS-secreted AexU effector from a diarrheal isolate SSU of Aeromonas hydrophila. The role of these toxin proteins in the pathogenesis of A. hydrop...

Molecular Characterization of a Functional Type VI Secretion System from a Clinical Isolate of Aeromonas hydrophilia

EPA Science Inventory

Our laboratory recently molecularly characterized the type II secretion system (T2SS)-associated cytotoxic enterotoxin (Act) and the T3SS-secreted AexU effector from a diarrheal isolate SSU of Aeromonas hydrophila. The role of these toxin proteins in the pathogenesis of A. hydrop...

Regulation of Effector Delivery by Type III Secretion Chaperone Proteins in Erwinia amylovora.

PubMed

Castiblanco, Luisa F; Triplett, Lindsay R; Sundin, George W

2018-01-01

Type III secretion (TTS) chaperones are critical for the delivery of many effector proteins from Gram-negative bacterial pathogens into host cells, functioning in the stabilization and hierarchical delivery of the effectors to the type III secretion system (TTSS). The plant pathogen Erwinia amylovora secretes at least four TTS effector proteins: DspE, Eop1, Eop3, and Eop4. DspE specifically interacts with the TTS chaperone protein DspF, which stabilizes the effector protein in the cytoplasm and promotes its efficient translocation through the TTSS. However, the role of E. amylovora chaperones in regulating the delivery of other secreted effectors is unknown. In this study, we identified functional interactions between the effector proteins DspE, Eop1, and Eop3 with the TTS chaperones DspF, Esc1 and Esc3 in yeast. Using site-directed mutagenesis, secretion, and translocation assays, we demonstrated that the three TTS chaperones have additive roles for the secretion and translocation of DspE into plant cells whereas DspF negatively affects the translocation of Eop1 and Eop3. Collectively, these results indicate that TTS chaperone proteins exhibit a cooperative behavior to orchestrate the effector secretion and translocation dynamics in E. amylovora .

Evaluation of Refractive Errors and Ocular Biometric Outcomes after Intravitreal Bevacizumab for Retinopathy of Prematurity.

PubMed

Gunay, Murat; Sekeroglu, Mehmet Ali; Bardak, Handan; Celik, Gokhan; Esenulku, Cenap Mahmut; Hekimoglu, Emre; Bardak, Yavuz

2016-06-01

To assess ocular biometric outcomes following intravitreal bevacizumab (IVB) monotherapy for retinopathy of prematurity (ROP) and compare these results with those of laser photocoagulated infants and with the ones with spontaneously regressed ROP. Premature infants including those who underwent IVB monotherapy (Group 1) or laser photocoagulation (Group 2) for ROP and infants with spontaneously regressed ROP (Group 3) were recruited for the study. Refractive errors and ocular biometric parameters (Axial length [AL], anterior chamber depth [ACD], and lens thickness [LT]) were measured at adjusted 1 year of age in all subjects. There was no significant difference of spherical equivalent (SE) value between the groups (P = 0.781). The incidence of high myopia was 7.4% in Group 1 and 12.7% in Group 2 (P = 0.081). No infants exhibited high myopia in Group 3. LT was greater in Group 2 when compared to Group 1 and Group 3 (P = 0.011). Lower SE was significantly correlated to longer AL in Group 1 (r = -0.656, P = 0.015). There was a significant positive correlation between SE and ACD values in Group 2 (r = 0.391, P = 0.005). The study showed no significant difference of SE between the groups. High myopia was only present among the treated infants either with IVB or laser. Infants who received laser treatment significantly had thicker lenses.

External Loops at the C Terminus of Erwinia chrysanthemi Pectate Lyase C Are Required for Species-Specific Secretion through the Out Type II Pathway

PubMed Central

Lindeberg, Magdalen; Boyd, Carol M.; Keen, Noel T.; Collmer, Alan

1998-01-01

The type II secretion system (main terminal branch of the general secretion pathway) is used by diverse gram-negative bacteria to secrete extracellular proteins. Proteins secreted by this pathway are synthesized with an N-terminal signal peptide which is removed upon translocation across the inner membrane, but the signals which target the mature proteins for secretion across the outer membrane are unknown. The plant pathogens Erwinia chrysanthemi and Erwinia carotovora secrete several isozymes of pectate lyase (Pel) by the out-encoded type II pathway. However, these two bacteria cannot secrete Pels encoded by heterologously expressed pel genes from the other species, suggesting the existence of species-specific secretion signals within these proteins. The functional cluster of E. chrysanthemi out genes carried on cosmid pCPP2006 enables Escherichia coli to secrete E. chrysanthemi, but not E. carotovora, Pels. We exploited the high sequence similarity between E. chrysanthemi PelC and E. carotovora Pel1 to construct 15 hybrid proteins in which different regions of PelC were replaced with homologous sequences from Pel1. The differential secretion of these hybrid proteins by E. coli(pCPP2006) revealed M118 to D175 and V215 to C329 as regions required for species-specific secretion of PelC. We propose that the primary targeting signal is contained within the external loops formed by G274 to C329 but is dependent on residues in M118 to D170 and V215 to G274 for proper positioning. PMID:9515910

Warfare between Host Immunity and Bacterial Weapons.

PubMed

Yu, Manda; Lai, Erh-Min

2017-01-11

Bacterial pathogens deploy protein secretion systems to facilitate infection and colonization of their hosts. In this issue of Cell Host & Microbe, Chen et al. (2017) report a new role for a type VI secretion effector in promoting bacterial colonization by preventing inflammasome activation induced by a type III secretion system. Copyright © 2017 Elsevier Inc. All rights reserved.

Discovery of the type VII ESX-1 secretion needle?

PubMed

Ates, Louis S; Brosch, Roland

2017-01-01

Mycobacterium tuberculosis, the etiological agent of human tuberculosis, harbours five ESAT-6/type VII secretion (ESX/T7S) systems. The first esx gene clusters were identified during the genome-sequencing project of M. tuberculosis H37Rv. Follow-up studies revealed additional genes playing important roles in ESX/T7S systems. Among the latter genes, one can find those that encode Pro-Glu (PE) and Pro-Pro-Glu (PPE) proteins as well as a gene cluster that is encoded >260 kb upstream of the esx-1 locus and encodes ESX-1 secretion-associated proteins EspA (Rv3616c), EspC (Rv3615c) and EspD (Rv3614c). The espACD cluster has been suggested to have an important function in ESX-1 secretion since EspA-EspC and EsxA-EsxB are mutually co-dependent on each other for secretion. However, the molecular mechanism of this co-dependence and interaction between the substrates remained unknown. In this issue of Molecular Microbiology, Lou and colleagues show that EspC forms high-molecular weight polymerization complexes that resemble selected components of type II, III and/or IV secretion systems of Gram-negative bacteria. Indeed, EspC-multimeric complexes form filamentous structures that could well represent a secretion needle of ESX-1 type VII secretion systems. This exciting observation opens new avenues for research to discover and characterize ESX/T7S components and elucidates the co-dependence of EsxA/B secretion with EspA/C. © 2016 John Wiley & Sons Ltd.

Activity in the Mission Control Center during Apollo 14

NASA Image and Video Library

1971-02-04

S71-17609 (4 Feb. 1971) --- These two individuals are examining a seismic reading in the Mission Control Center's ALSEP Room during the Apollo 14 S-IVB impact on the moon. Dr. Maurice Ewing (left) is the director of the Lamont-Doherty Geological Observatory at Columbia University. David Lammlein, a Columbia graduate student, is on the right. The Apollo 14 Saturn IVB stage impacted on the lunar surface at 1:40:54 a.m. (CST), Feb. 4, 1971, about 90 nautical miles south-southwest of the Apollo 12 passive seismometer. The energy release was comparable to 11 tons of TNT. Dr. Gary Latham of the Lamont-Doherty Geological Observatory is the principal investigator for the Passive Seismic Experiment, a component of the Apollo Lunar Surface Experiments Package.

View of the Saturn V third stage from which the Apollo 8 has separated

NASA Image and Video Library

1968-12-21

AS08-16-2584 (21 Dec. 1968) --- This is a photograph taken from the Apollo 8 spacecraft looking back at the Saturn V third (S-IVB) stage from which the spacecraft had just separated following trans-lunar injection. Attached to the S-IVB is the Lunar Module Test Article (LTA) which simulated the mass of a Lunar Module (LM) on the Apollo 8 lunar orbit mission. The 29-feet panels of the Spacecraft LM Adapter which enclosed the LTA during launch have already been jettisoned and are out of view. Sunlight reflected from small particles shows the "firefly" phenomenon which was reported by astronaut John H. Glenn Jr. during the first Earth-orbital flight, Mercury-Atlas 6 (MA-6) of the Mercury Program.

View of the Saturn V third stage from which the Apollo 8 has separated

NASA Image and Video Library

1968-12-21

AS08-16-2583 (21 Dec. 1968) --- This is a photograph taken from the Apollo 8 spacecraft looking back at the Saturn V third (S-IVB) stage from which the spacecraft had just separated following trans-lunar injection. Attached to the S-IVB is the Lunar Module Test Article (LTA) which simulated the mass of a Lunar Module (LM) on the Apollo 8 lunar orbit mission. The 29-feet panels of the Spacecraft LM Adapter which enclosed the LTA during launch have already been jettisoned and are out of view. Sunlight reflected from small particles shows the "firefly" phenomenon which was reported by astronaut John H. Glenn Jr. during the first Earth-orbital flight, Mercury-Atlas 6 (MA-6) of the Mercury Program.

VX-970, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-06-11

Head and Neck Squamous Cell Carcinoma; Human Papillomavirus Negative; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7

S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-04-09

Colon Adenocarcinoma; ERBB2 Gene Amplification; Rectal Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage III Colon Cancer AJCC v7; Stage III Rectal Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Colon Cancer AJCC v7; Stage IV Rectal Cancer AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7

Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer

ClinicalTrials.gov

2018-05-23

Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Follicular Carcinoma AJCC v7; Stage I Thyroid Gland Papillary Carcinoma AJCC v7; Stage II Thyroid Gland Follicular Carcinoma AJCC v7; Stage II Thyroid Gland Papillary Carcinoma AJCC v7; Stage III Thyroid Gland Follicular Carcinoma AJCC v7; Stage III Thyroid Gland Papillary Carcinoma AJCC v7; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7

Efficient extracellular production of type I secretion pathway-dependent Pseudomonas fluorescens lipase in recombinant Escherichia coli by heterologous ABC protein exporters.

PubMed

Eom, Gyeong Tae; Lee, Seung Hwan; Oh, Young Hoon; Choi, Ji Eun; Park, Si Jae; Song, Jae Kwang

2014-10-01

Heterologous ABC protein exporters, the apparatus of type I secretion pathway in Gram-negative bacteria, were used for extracellular production of Pseudomonas fluorescens lipase (TliA) in recombinant Escherichia coli. The effect of the expression of different ABC protein exporter gene clusters (P. fluorescens tliDEF, Pseudomonas aeruginosa aprDEF, Erwinia chrysanthemi prtDEF, and Serratia marcescens lipBCD genes) was examined on the secretion of TliA at growth temperatures of 20, 25, 30 and 35 °C. TliA secretion in recombinant E. coli XL10-Gold varied depending upon type of ABC protein exporter and culture temperature. E. coli expressing S. marcescens lipBCD genes showed the highest secretion level of TliA (122.8 U ml(-1)) when cultured at 25 °C. Thus, optimized culture conditions for efficient extracellular production of lipase in recombinant E. coli can be designed by changing the type of ABC protein exporter and the growth temperature.

System of matrix metalloproteinases and cytokine secretion in type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension.

PubMed

Kologrivova, I V; Suslova, T E; Koshel'skaya, O A; Vinnitskaya, I V; Trubacheva, O A

2014-03-01

The study included patients with type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension, patients with arterial hypertension, and healthy volunteers. We evaluated the levels of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase type 1 (TIMP-1), glucose, insulin, C-peptide, glycated hemoglobin, and spontaneous and mitogen-activated cytokine secretion (IL-2, IL4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ). Patients with type 2 diabetes mellitus in combination with arterial hypertension exhibited maximum TIMP-1 levels and TIMP-1/MMP-2, TIMP-1/ MMP-9 ratios as well as enhanced secretion of TNF-α, IL-6, IL-17 and reduced secretion of IL-10 in comparison with healthy individuals. The observed shifts are probably determined the development of systemic hyperinsulinemia in patients suffering from type 2 diabetes mellitus coupled with arterial hypertension.

YscU/FlhB of Yersinia pseudotuberculosis Harbors a C-terminal Type III Secretion Signal*

PubMed Central

Login, Frédéric H.; Wolf-Watz, Hans

2015-01-01

All type III secretion systems (T3SS) harbor a member of the YscU/FlhB family of proteins that is characterized by an auto-proteolytic process that occurs at a conserved cytoplasmic NPTH motif. We have previously demonstrated that YscUCC, the C-terminal peptide generated by auto-proteolysis of Yersinia pseudotuberculosis YscU, is secreted by the T3SS when bacteria are grown in Ca2+-depleted medium at 37 °C. Here, we investigated the secretion of this early T3S-substrate and showed that YscUCC encompasses a specific C-terminal T3S signal within the 15 last residues (U15). U15 promoted C-terminal secretion of reporter proteins like GST and YopE lacking its native secretion signal. Similar to the “classical” N-terminal secretion signal, U15 interacted with the ATPase YscN. Although U15 is critical for YscUCC secretion, deletion of the C-terminal secretion signal of YscUCC did neither affect Yop secretion nor Yop translocation. However, these deletions resulted in increased secretion of YscF, the needle subunit. Thus, these results suggest that YscU via its C-terminal secretion signal is involved in regulation of the YscF secretion. PMID:26338709

Structural and functional dissection reveals distinct roles of Ca2+-binding sites in the giant adhesin SiiE of Salmonella enterica

PubMed Central

Klingl, Stefan; Sandmann, Achim; Taccardi, Nicola; Sticht, Heinrich; Muller, Yves A.; Hensel, Michael

2017-01-01

The giant non-fimbrial adhesin SiiE of Salmonella enterica mediates the first contact to the apical site of epithelial cells and enables subsequent invasion. SiiE is a 595 kDa protein composed of 53 repetitive bacterial immunoglobulin (BIg) domains and the only known substrate of the SPI4-encoded type 1 secretion system (T1SS). The crystal structure of BIg50-52 of SiiE revealed two distinct Ca2+-binding sites per BIg domain formed by conserved aspartate or glutamate residues. In a mutational analysis Ca2+-binding sites were disrupted by aspartate to serine exchange at various positions in the BIg domains of SiiE. Amounts of secreted SiiE diminish with a decreasing number of intact Ca2+-binding sites. BIg domains of SiiE contain distinct Ca2+-binding sites, with type I sites being similar to other T1SS-secreted proteins and type II sites newly identified in SiiE. We functionally and structurally dissected the roles of type I and type II Ca2+-binding sites in SiiE, as well as the importance of Ca2+-binding sites in various positions of SiiE. Type I Ca2+-binding sites were critical for efficient secretion of SiiE and a decreasing number of type I sites correlated with reduced secretion. Type II sites were less important for secretion, stability and surface expression of SiiE, however integrity of type II sites in the C-terminal portion was required for the function of SiiE in mediating adhesion and invasion. PMID:28558023

Computational prediction of type III and IV secreted effectors in Gram-negative bacteria

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

McDermott, Jason E.; Corrigan, Abigail L.; Peterson, Elena S.

2011-01-01

In this review, we provide an overview of the methods employed by four recent papers that described novel methods for computational prediction of secreted effectors from type III and IV secretion systems in Gram-negative bacteria. The results of the studies in terms of performance at accurately predicting secreted effectors and similarities found between secretion signals that may reflect biologically relevant features for recognition. We discuss the web-based tools for secreted effector prediction described in these studies and announce the availability of our tool, the SIEVEserver (http://www.biopilot.org). Finally, we assess the accuracy of the three type III effector prediction methods onmore » a small set of proteins not known prior to the development of these tools that we have recently discovered and validated using both experimental and computational approaches. Our comparison shows that all methods use similar approaches and, in general arrive at similar conclusions. We discuss the possibility of an order-dependent motif in the secretion signal, which was a point of disagreement in the studies. Our results show that there may be classes of effectors in which the signal has a loosely defined motif, and others in which secretion is dependent only on compositional biases. Computational prediction of secreted effectors from protein sequences represents an important step toward better understanding the interaction between pathogens and hosts.« less

Identification and characterization of a type III secretion-associated chaperone in the type III secretion system 1 of Vibrio parahaemolyticus.

PubMed

Akeda, Yukihiro; Okayama, Kanna; Kimura, Tomomi; Dryselius, Rikard; Kodama, Toshio; Oishi, Kazunori; Iida, Tetsuya; Honda, Takeshi

2009-07-01

Vibrio parahaemolyticus causes human gastroenteritis. Genomic sequencing of this organism has revealed that it has two sets of type III secretion systems, T3SS1 and T3SS2, both of which are important for its pathogenicity. However, the mechanism of protein secretion via T3SSs is unknown. A characteristic of many effectors is that they require specific chaperones for efficient delivery via T3SSs; however, no chaperone has been experimentally identified in the T3SSs of V. parahaemolyticus. In this study, we identified candidate T3SS1-associated chaperones from genomic sequence data and examined their roles in effector secretion/translocation and binding to their cognate substrates. From these experiments, we concluded that there is a T3S-associated chaperone, VecA, for a cytotoxic T3SS1-dependent effector, VepA. Further analysis using pulldown and secretion assays characterized the chaperone-binding domain encompassing the first 30-100 amino acids and an amino terminal secretion signal encompassing the first 5-20 amino acids on VepA. These findings will provide a strategy to clarify how the T3SS1 of V. parahaemolyticus secretes its specific effectors.

Information Hiding In Digital Video Using DCT, DWT and CvT

NASA Astrophysics Data System (ADS)

Abed Shukur, Wisam; Najah Abdullah, Wathiq; Kareem Qurban, Luheb

2018-05-01

The type of video that used in this proposed hiding a secret information technique is .AVI; the proposed technique of a data hiding to embed a secret information into video frames by using Discrete Cosine Transform (DCT), Discrete Wavelet Transform (DWT) and Curvelet Transform (CvT). An individual pixel consists of three color components (RGB), the secret information is embedded in Red (R) color channel. On the receiver side, the secret information is extracted from received video. After extracting secret information, robustness of proposed hiding a secret information technique is measured and obtained by computing the degradation of the extracted secret information by comparing it with the original secret information via calculating the Normalized cross Correlation (NC). The experiments shows the error ratio of the proposed technique is (8%) while accuracy ratio is (92%) when the Curvelet Transform (CvT) is used, but compared with Discrete Wavelet Transform (DWT) and Discrete Cosine Transform (DCT), the error rates are 11% and 14% respectively, while the accuracy ratios are (89%) and (86%) respectively. So, the experiments shows the Poisson noise gives better results than other types of noises, while the speckle noise gives worst results compared with other types of noises. The proposed technique has been established by using MATLAB R2016a programming language.

Atlantic salmon endothelial cells from the heart were more susceptible than fibroblasts from the bulbus arteriosus to four RNA viruses but protected from two viruses by dsRNA pretreatment.

PubMed

Pham, Phuc H; Tong, Winnie W L; Misk, Ehab; Jones, Ginny; Lumsden, John S; Bols, Niels C

2017-11-01

Heart diseases caused by viruses are major causes of Atlantic salmon aquaculture loss. Two Atlantic salmon cardiovascular cell lines, an endothelial cell line (ASHe) from the heart and a fibroblast cell line (BAASf) from the bulbus arteriosus, were evaluated for their response to four fish viruses, CSV, IPNV, VHSV IVa and VHSV IVb, and the innate immune agonist, double-stranded RNA mimic poly IC. All four viruses caused cytopathic effects in ASHe and BAASf. However, ASHe was more susceptible to all four viruses than BAASf. When comparing between the viruses, ASHe cells were found to be moderately susceptible to CSV and VHSV IVb, but highly susceptible to IPNV and VHSV IVa induced cell death. All four viruses were capable of propagating in the ASHe cell line, leading to increases in virus titre over time. In BAASf, CSV and IPNV produced more than one log increase in titre from initial infection, but VHSV IVb and IVa did not. When looking at the antiviral response of both cell lines, Mx proteins were induced in ASHe and BAASf by poly IC. All four viruses induced Mx proteins in BAASf, while only CSV and VHSV IVb induced Mx proteins in ASHe. IPNV and VHSV IVa suppressed Mx proteins expression in ASHe. Pretreatment of ASHe with poly IC to allow for Mx proteins accumulation protected the culture from subsequent infections with IPNV and VHSV IVa, resulting in delayed cell death, reduced virus titres and reduced viral proteins expression. These data suggest that endothelial cells potentially can serve as points of infections for viruses in the heart and that two of the four viruses, IPNV and VHSV IVa, have mechanisms to avoid or downregulate antiviral responses in ASHe cells. Furthermore, the high susceptibility of the ASHe cell line to IPNV and VHSV IVa can make it a useful tool for studying antiviral compounds against these viruses and for general detection of fish viruses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protecting Trade Secrets in Canada

PubMed Central

Courage, Noel; Calzavara, Janice

2015-01-01

Patents in the life sciences industries are a key form of intellectual property (IP), particularly for products such as brand-name drugs and medical devices. However, trade secrets can also be a useful tool for many types of innovations. In appropriate cases, trade secrets can offer long-term protection of IP for a lower financial cost than patenting. This type of protection must be approached with caution as there is little room for error when protecting a trade secret. Strong agreements and scrupulous security can help to protect the secret. Once a trade secret is disclosed to the public, it cannot be restored as the owner's property; however, if the information is kept from the public domain, the owner can have a property right of unlimited duration in the information. In some situations patents and trade secrets may be used cooperatively to protect innovation, particularly for manufacturing processes. PMID:25986591

FDG and FMISO PET Hypoxia Evaluation in Cervical Cancer

ClinicalTrials.gov

2016-12-28

Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

Cervical Cancer Stage IVB

MedlinePlus

... drawing shows other parts of the body where cervical cancer may spread, including the lymph nodes, lung, liver, intestinal tract, and bone. An inset shows cancer cells spreading from the cervix, through the blood and ...

The type III secreted effector DspE is required early in Solanum tuberosum leaf infection by Pectobacterium carotovorum to elicit cell death, and requires Wx(3-6)D/E motifs

USDA-ARS?s Scientific Manuscript database

Pectobacterium species are enterobacterial plant-pathogens that cause soft rot disease in diverse plant species. Unlike hemi-biotrophic plant pathogenic bacteria, the type III secretion system (T3SS) of Pectobacterium carotovorum subsp. carotovorum (P. carotovorum) appears to secrete only one effect...

Introduction and evolution of dengue virus type 2 in Pakistan: a phylogeographic analysis.

PubMed

Akram, Madiha; Fatima, Zareen; Purdy, Mike A; Sue, Amanda; Saleem, Sana; Amin, Irum; Shahid, Muhammad; Idrees, Muhammad; Nawaz, Rabia

2015-09-22

Pattern of Dengue periodic epidemics through the years along with sporadic cases of Dengue hemorrhagic fever followed by a severe 2011 epidemic of Dengue fever in Pakistan make Pakistan a Dengue endemic country. To study the entry and evolution of dengue virus serotype 2 (DENV-2) in Pakistan, we sequenced three full length genomes and 24 complete envelope sequences of DENV-2 from the years 2010, 2011 and 2013 collected from Punjab province of Pakistan. Phylogenetic and Bayesian phylogeographic analyses was applied to three full genome sequences as well as 24 envelope sequences to study the spatiotemporal dynamics of DENV-2 in Pakistan. Most of the DENV-2 viruses from the years 2008 to 2013 formed a monophyletic Pakistani clade in IVb sublineage of cosmopolitan genotype except one 2008 DENV-2 strain. Phylogeographic analysis revealed that this 2008 DENV-2 strain was rooted to India 25.4 years ago with a location probability of 0.88. However Pakistani clade rooted back to Sri Lanka 12.6 years ago with a location probability of 0.57. DENV-2 genotype IV was introduced in Pakistan in two time events. First event was introduction from India to Pakistan in the late 1980s (around 1986), and second event was introduction from Sri Lanka to Pakistan around 2000. The later introduction event was responsible for major outbreaks in the Punjab region of Pakistan, including major 2011 outbreak. After the second Introduction event, DENV-2 circulated locally in the region forming a distinct Sublineage within the IVb cosmopolitan genotype of DENV-2.

Solution Structure of Homology Region (HR) Domain of Type II Secretion System*

PubMed Central

Gu, Shuang; Kelly, Geoff; Wang, Xiaohui; Frenkiel, Tom; Shevchik, Vladimir E.; Pickersgill, Richard W.

2012-01-01

The type II secretion system of Gram-negative bacteria is important for bacterial pathogenesis and survival; it is composed of 12 mostly multimeric core proteins, which build a sophisticated secretion machine spanning both bacterial membranes. OutC is the core component of the inner membrane subcomplex thought to be involved in both recognition of substrate and interaction with the outer membrane secretin OutD. Here, we report the solution structure of the HR domain of OutC and explore its interaction with the secretin. The HR domain adopts a β-sandwich-like fold consisting of two β-sheets each composed of three anti-parallel β-strands. This structure is strikingly similar to the periplasmic region of PilP, an inner membrane lipoprotein from the type IV pilus system highlighting the common evolutionary origin of these two systems and showing that all the core components of the type II secretion system have a structural or sequence ortholog within the type IV pili system. The HR domain is shown to interact with the N0 domain of the secretin. The importance of this interaction is explored in the context of the functional secretion system. PMID:22253442

YscU/FlhB of Yersinia pseudotuberculosis Harbors a C-terminal Type III Secretion Signal.

PubMed

Login, Frédéric H; Wolf-Watz, Hans

2015-10-23

All type III secretion systems (T3SS) harbor a member of the YscU/FlhB family of proteins that is characterized by an auto-proteolytic process that occurs at a conserved cytoplasmic NPTH motif. We have previously demonstrated that YscUCC, the C-terminal peptide generated by auto-proteolysis of Yersinia pseudotuberculosis YscU, is secreted by the T3SS when bacteria are grown in Ca(2+)-depleted medium at 37 °C. Here, we investigated the secretion of this early T3S-substrate and showed that YscUCC encompasses a specific C-terminal T3S signal within the 15 last residues (U15). U15 promoted C-terminal secretion of reporter proteins like GST and YopE lacking its native secretion signal. Similar to the "classical" N-terminal secretion signal, U15 interacted with the ATPase YscN. Although U15 is critical for YscUCC secretion, deletion of the C-terminal secretion signal of YscUCC did neither affect Yop secretion nor Yop translocation. However, these deletions resulted in increased secretion of YscF, the needle subunit. Thus, these results suggest that YscU via its C-terminal secretion signal is involved in regulation of the YscF secretion. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The role of intrinsic disorder and dynamics in the assembly and function of the type II secretion system.

PubMed

Gu, Shuang; Shevchik, Vladimir E; Shaw, Rosie; Pickersgill, Richard W; Garnett, James A

2017-10-01

Many Gram-negative commensal and pathogenic bacteria use a type II secretion system (T2SS) to transport proteins out of the cell. These exported proteins or substrates play a major role in toxin delivery, maintaining biofilms, replication in the host and subversion of host immune responses to infection. We review the current structural and functional work on this system and argue that intrinsically disordered regions and protein dynamics are central for assembly, exo-protein recognition, and secretion competence of the T2SS. The central role of intrinsic disorder-order transitions in these processes may be a particular feature of type II secretion. Copyright © 2017 Elsevier B.V. All rights reserved.

Programs To Support You During Chemotherapy

ClinicalTrials.gov

2018-05-24

Depression; Fatigue; Stage IIA Colorectal Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Colorectal Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

Activity in the Mission Control Center during Apollo 14

NASA Image and Video Library

1971-02-04

S71-17610 (4 Feb. 1971) --- Partial view of activity in the Mission Operations Control Room in the Mission Control Center at the time the Apollo 14 S-IVB stage impacted on the lunar surface. The flight director's console is in the foreground. Eugene F. Kranz, chief of the MSC Flight Control Division, is in the right foreground. Seated at the console is Glynn S. Lunney, head of the Flight Director Office, Flight Control Division. Facing the camera is Gerald D. Griffin, flight director of the Third (Gold) Team. A seismic reading from the impact can be seen in the center background. The S-IVB impacted on the lunar surface at 1:40:54 a.m. (CST), Feb. 4, 1971, about 90 nautical miles south-southwest of the Apollo 12 passive seismometer. The energy release was comparable to 11 tons of TNT.

Skylab

NASA Image and Video Library

1968-01-01

This photograph was taken at the Redstone airfield, Huntsville, Alabama, during the unloading of the Saturn V S-IVB stage that housed the Orbital Workshop (OWS) from the Super Guppy, the NASA plane that was specially built to carry oversized cargo. The OWS measured 22 feet (6.7 m) in diameter, and 48 feet (14.6 m) in length. The Saturn V S-IVB stage was modified at the McDornell Douglas facility at Huntington Beach, California, for a new role, which was to house the OWS. In addition to the test articles, engineering mockups, and flight equipment, both McDonnell Douglas and Martin Marietta built 0-G trainers, neutral buoyancy trainers, and high-fidelity mockups for the 1-G trainer to be used in the KC-135 aircraft. The Marshall Space Flight Center had program management responsibility for the development of Skylab hardware and experiments.

Incidence of Endophthalmitis after Intravitreal Bevacizumab using Aliquots Prepared On-site in 2 Operating Rooms in Kuwait

PubMed Central

Wani, Vivek B.; Al-Kandari, Jamal; Sabti, Khalid; Aljassar, Faisal; Qali, Hussain; Kumar, Niranjan; Uboweja, Anilkumar; Al-Sabah, Khalid; Diab, Fahad A.; Al-Rashidi, Saleh

2016-01-01

Purpose: To report the incidence of endophthalmitis after intravitreal injection of bevacizumab and the outcomes of treatment of endophthalmitis at two centers in Kuwait. Subjects and Methods: The aliquots of bevacizumab were prepared under aseptic precautions and administered in the operating theater on the same day at both centers. All patients received antibiotic drops after injection of bevacizumab. Data were collected on the number of cases that received intravitreal bevacizumab (IVB) and those that developed endophthalmitis were identified at the two centers. All cases of endophthalmitis received an intravitreal antibiotic injection and additional treatments as warranted. Data were collected on the outcomes of endophthalmitis treatment. Results: There were 5 cases of endophthalmitis among a total of 5429 injections (0.09%: Confidence interval: 0.084–0.1). The incidence was 3 cases among 4690 (0.06%) and 2 cases among 739 injections (0.027%) at each center, respectively (P = 0.08). Four cases of endophthalmitis were culture-positive and organisms isolated were, coagulase negative Staphylococcus in 2 cases, Staphylococcus lugdunensis and Streptococcus pneumoniae in 1 case each. The final visual acuity was better than pre-IVB in 3 cases, same as pre-IVB in 1 case and worse in 1 case with streptococcal infection. No eyes developed phthisis bulbi or required enucleation. Conclusions: The incidence of endophthalmitis after intravitreal injection of bevacizumab using aliquots prepared in the operating room is comparable to other studies. There were no clusters of endophthalmitis cases. PMID:26957841

Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck

ClinicalTrials.gov

2013-01-08

Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx

Efficacy of Intravitreal Anti-vascular Endothelial Growth Factor or Steroid Injection in Diabetic Macular Edema According to Fluid Turbidity in Optical Coherence Tomography

PubMed Central

Lee, Kyungmin; Chung, Heeyoung; Park, Youngsuk

2014-01-01

Purpose To determine if short term effects of intravitreal anti-vascular endothelial growth factor or steroid injection are correlated with fluid turbidity, as detected by spectral domain optical coherence tomography (SD-OCT) in diabetic macular edema (DME) patients. Methods A total of 583 medical records were reviewed and 104 cases were enrolled. Sixty eyes received a single intravitreal bevacizumab injection (IVB) on the first attack of DME and 44 eyes received triamcinolone acetonide treatment (IVTA). Intraretinal fluid turbidity in DME patients was estimated with initialintravitreal SD-OCT and analyzed with color histograms from a Photoshop program. Central macular thickness and visual acuity using a logarithm from the minimum angle of resolution chart, were assessed at the initial period and 2 months after injections. Results Visual acuity and central macular thickness improved after injections in both groups. In the IVB group, visual acuity and central macular thickness changed less as the intraretinal fluid became more turbid. In the IVTA group, visual acuity underwent less change while central macular thickness had a greater reduction (r = -0.675, p = 0.001) as the intraretinal fluid was more turbid. Conclusions IVB and IVTA injections were effective in reducing central macular thickness and improving visual acuity in DME patients. Further, fluid turbidity, which was detected by SD-OCT may be one of the indexes that highlight the influence of the steroid-dependent pathogenetic mechanism. PMID:25120338

Efficacy of intravitreal anti-vascular endothelial growth factor or steroid injection in diabetic macular edema according to fluid turbidity in optical coherence tomography.

PubMed

Lee, Kyungmin; Chung, Heeyoung; Park, Youngsuk; Sohn, Joonhong

2014-08-01

To determine if short term effects of intravitreal anti-vascular endothelial growth factor or steroid injection are correlated with fluid turbidity, as detected by spectral domain optical coherence tomography (SD-OCT) in diabetic macular edema (DME) patients. A total of 583 medical records were reviewed and 104 cases were enrolled. Sixty eyes received a single intravitreal bevacizumab injection (IVB) on the first attack of DME and 44 eyes received triamcinolone acetonide treatment (IVTA). Intraretinal fluid turbidity in DME patients was estimated with initial intravitreal SD-OCT and analyzed with color histograms from a Photoshop program. Central macular thickness and visual acuity using a logarithm from the minimum angle of resolution chart, were assessed at the initial period and 2 months after injections. Visual acuity and central macular thickness improved after injections in both groups. In the IVB group, visual acuity and central macular thickness changed less as the intraretinal fluid became more turbid. In the IVTA group, visual acuity underwent less change while central macular thickness had a greater reduction (r = -0.675, p = 0.001) as the intraretinal fluid was more turbid. IVB and IVTA injections were effective in reducing central macular thickness and improving visual acuity in DME patients. Further, fluid turbidity, which was detected by SD-OCT may be one of the indexes that highlight the influence of the steroid-dependent pathogenetic mechanism.

Metastable Structural Phases of Metals in Columns IVB to Vib, and Rows 4 TO 6 OF the Periodic Table

NASA Astrophysics Data System (ADS)

Nnolim, Neme; Tyson, Trevor

2002-03-01

Total energy calculations as a function of strain along the <001> direction have been carried out for the bcc metals V, Nb, Ta, Cr, Mo and W, and the hcp metals Ti, Zr and Hf, all in the block of the periodic table defined by columns IVB to VIB, and rows 4 to 6. Since strain along the <001> direction corresponds to variation of the c lattice constant with respect to the a lattice constant, the total energy per unit cell has being calculated as a function of the c/a ratio. The highly accurate FP-LAPW (Full Potential Linearized Augmented Plane Wave) band structure method in the DFT (Density Functional Theory) formalism has been used for the calculations. In all cases except for the hcp column IVB elements, Zr, Hf and Ti, a metastable state was predicted from the calculations. Electronic properties are computed for all structures and are correlated with electrical and mechanical properties of metastable phases that have been observed experimentally. Properties of metastable phases, which were predicted in this work but which as of yet have not been observed experimentally, have also been predicted. Special attention is paid to the phases of tantalum and calculated transport properties are used to show that the observed high resistivity of the beta phase of tantalum relative to the alpha bcc phase cannot be explained solely by simple tetragonal distortions of the bcc phase.

Type 1 Does The Two-Step: Type 1 Secretion Substrates With A Functional Periplasmic Intermediate.

PubMed

Smith, Timothy J; Sondermann, Holger; O'Toole, George A

2018-06-04

Bacteria have evolved several secretion strategies for polling and responding to environmental flux and insult. Of these, the type 1 secretion system (T1SS) is known to secrete an array of biologically diverse proteins - from small < 10 kDa bacteriocins to gigantic adhesins with a mass over 1 MDa. For the last several decades T1SS have been characterized as a one-step translocation strategy whereby the secreted substrate is transported directly into the extracellular environment from the cytoplasm with no periplasmic intermediate. Recent phylogenetic, biochemical, and genetic evidence point to a distinct sub-group of T1SS machinery linked with a bacterial transglutaminase-like cysteine proteinase (BTLCP), which uses a two-step secretion mechanism. BTLCP-linked T1SS transport a class of repeats-in-toxin (RTX) adhesins that are critical for biofilm formation. The prototype of this RTX adhesin group, LapA of Pseudomonas fluorescens Pf0-1, uses a novel N-terminal retention module to anchor the adhesin at the cell surface as a secretion intermediate threaded through the outer membrane-localized, TolC-like protein LapE. This secretion intermediate is post-translationally cleaved by the BTLCP family LapG protein to release LapA from its cognate T1SS pore. Thus, secretion of LapA and related RTX adhesins into the extracellular environment appears to be a T1SS-mediated, two-step process that involves a periplasmic intermediate. In this review, we contrast the T1SS machinery and substrates of the BLTCP-linked two-step secretion process with those of the classical one-step T1SS to better understand the newly recognized and expanded role of this secretion machinery. Copyright © 2018 American Society for Microbiology.

Native structure of a type IV secretion system core complex essential for Legionella pathogenesis.

PubMed

Kubori, Tomoko; Koike, Masafumi; Bui, Xuan Thanh; Higaki, Saori; Aizawa, Shin-Ichi; Nagai, Hiroki

2014-08-12

Bacterial type IV secretion systems are evolutionarily related to conjugation systems and play a pivotal role in infection by delivering numerous virulence factors into host cells. Using transmission electron microscopy, we report the native molecular structure of the core complex of the Dot/Icm type IV secretion system encoded by Legionella pneumophila, an intracellular human pathogen. The biochemically isolated core complex, composed of at least five proteins--DotC, DotD, DotF, DotG, and DotH--has a ring-shaped structure. Intriguingly, morphologically distinct premature complexes are formed in the absence of DotG or DotF. Our data suggest that DotG forms a central channel spanning inner and outer membranes. DotF, a component dispensable for type IV secretion, plays a role in efficient embedment of DotG into the functional core complex. These results highlight a common scheme for the biogenesis of transport machinery.

Incretin secretion in obese Korean children and adolescents with newly diagnosed type 2 diabetes.

PubMed

Park, So Hyun; Jung, Min Ho; Cho, Won Kyoung; Park, Mi Sun; Suh, Byung Kyu

2016-01-01

The role of incretins in type 2 diabetes is controversial. This study investigated the association between incretin levels in obese Korean children and adolescents newly diagnosed with type 2 diabetes. We performed a 2-hr oral glucose tolerance test (OGTT) in obese children and adolescents with type 2 diabetes and with normal glucose tolerance. Twelve obese children and adolescents with newly diagnosed type 2 diabetes (DM group) and 12 obese age-matched subjects without type 2 diabetes (NDM group) were included. An OGTT was conducted and insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were measured during the OGTT. The mean age of the patients was 13·8 ± 2·0 years, and the mean body mass index (BMI) Z-score was 2·1 ± 0·5. The groups were comparable in age, sex, BMI Z-score and waist:hip ratio. The DM group had significantly lower homeostasis model assessment of β and insulinogenic index values (P < 0·001). The homeostasis model assessment of insulin resistance index was not different between the two groups. Insulin and C-peptide secretions were significantly lower in the DM group than in the NDM group (P < 0·001). Total GLP-1 secretion was significantly higher in the DM group while intact GLP-1 and GIP secretion values were not significantly different between the two groups. Impaired insulin secretion might be important in the pathogenesis of type 2 diabetes in obese Korean children and adolescents, however, which may not be attributed to incretin secretion. © 2015 John Wiley & Sons Ltd.

Reduced-Dose Intensity-Modulated Radiation Therapy With or Without Cisplatin in Treating Patients With Advanced Oropharyngeal Cancer

ClinicalTrials.gov

2018-01-08

Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma

20 CFR 638.301 - Funding procedures.

Code of Federal Regulations, 2010 CFR

2010-04-01

... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Funding, Site Selection, and Facilities Management § 638... and negotiated management fee of not less than 1 percent of the contract amount. [55 FR 12996, Apr. 6...

20 CFR 638.519 - Incentives system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.519 Incentives system. The center... established by the Job Corps Director. ...

Optical properties of the uropygial gland secretion: no evidence for UV cosmetics in birds

NASA Astrophysics Data System (ADS)

Delhey, Kaspar; Peters, Anne; Biedermann, Peter H. W.; Kempenaers, Bart

2008-10-01

Ultraviolet (UV) reflectance of the plumage is common in birds and plays an important role in sexual signalling. Recently, it has been proposed that birds are able to modify plumage UV reflectance by the application of uropygial gland secretion. Based on a survey of the optical properties of this secretion from 51 species belonging to 12 avian orders, we show that two main types of uropygial secretions exist, one predominantly found in passerines and one in non-passerines, both reducing relative UV reflectance of a white background (Teflon™ tape). We quantified how each type of secretion (exemplified by blue tit and mallard) affected feather UV reflectance. Both secretions reduced overall brightness and relative UV reflectance of white mallard feathers but hardly affected the reflectance of UV/blue blue tit crown feathers. According to models of avian colour vision, changes in reflectance due to application of the secretion were at or below the discrimination threshold of most birds. We conclude that the uropygial secretion is unlikely to play a major role in modifying plumage UV reflectance. However, the optical properties of the uropygial secretion may have been selected to interfere as little as possible with visual signaling through plumage reflectance.

Structure of Salmonella FlhE, conserved member of a flagellar Type III secretion operon

DOE PAGES

Lee, Jaemin; Monzingo, Arthur F.; Keatinge-Clay, Adrian T.; ...

2014-12-26

In this paper, the bacterial flagellum is assembled by a multicomponent transport apparatus categorized as a type III secretion system. The secretion of proteins that assemble into the flagellum is driven by the proton motive force. The periplasmic protein FlhE is a member of the flhBAE operon in the majority of bacteria where FlhE is found. FlhA and FlhB are established components of the flagellar type III secretion system. The absence of FlhE results in a proton leak through the flagellar system, inappropriate secretion patterns, and cell death, indicating that FlhE regulates an important aspect of proper flagellar biosynthesis. Wemore » isolated FlhE from the periplasm of Salmonella and solved its structure to 1.5 Å resolution. The structure reveals a β-sandwich fold, with no close structural homologs. Finally, possible roles of FlhE, including that of a chaperone, are discussed.« less

Structure of Salmonella FlhE, conserved member of a flagellar Type III secretion operon

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

Lee, Jaemin; Monzingo, Arthur F.; Keatinge-Clay, Adrian T.

In this paper, the bacterial flagellum is assembled by a multicomponent transport apparatus categorized as a type III secretion system. The secretion of proteins that assemble into the flagellum is driven by the proton motive force. The periplasmic protein FlhE is a member of the flhBAE operon in the majority of bacteria where FlhE is found. FlhA and FlhB are established components of the flagellar type III secretion system. The absence of FlhE results in a proton leak through the flagellar system, inappropriate secretion patterns, and cell death, indicating that FlhE regulates an important aspect of proper flagellar biosynthesis. Wemore » isolated FlhE from the periplasm of Salmonella and solved its structure to 1.5 Å resolution. The structure reveals a β-sandwich fold, with no close structural homologs. Finally, possible roles of FlhE, including that of a chaperone, are discussed.« less

Comparative Pan-Genome Analysis of Piscirickettsia salmonis Reveals Genomic Divergences within Genogroups.

PubMed

Nourdin-Galindo, Guillermo; Sánchez, Patricio; Molina, Cristian F; Espinoza-Rojas, Daniela A; Oliver, Cristian; Ruiz, Pamela; Vargas-Chacoff, Luis; Cárcamo, Juan G; Figueroa, Jaime E; Mancilla, Marcos; Maracaja-Coutinho, Vinicius; Yañez, Alejandro J

2017-01-01

Piscirickettsia salmonis is the etiological agent of salmonid rickettsial septicemia, a disease that seriously affects the salmonid industry. Despite efforts to genomically characterize P. salmonis , functional information on the life cycle, pathogenesis mechanisms, diagnosis, treatment, and control of this fish pathogen remain lacking. To address this knowledge gap, the present study conducted an in silico pan-genome analysis of 19 P. salmonis strains from distinct geographic locations and genogroups. Results revealed an expected open pan-genome of 3,463 genes and a core-genome of 1,732 genes. Two marked genogroups were identified, as confirmed by phylogenetic and phylogenomic relationships to the LF-89 and EM-90 reference strains, as well as by assessments of genomic structures. Different structural configurations were found for the six identified copies of the ribosomal operon in the P. salmonis genome, indicating translocation throughout the genetic material. Chromosomal divergences in genomic localization and quantity of genetic cassettes were also found for the Dot/Icm type IVB secretion system. To determine divergences between core-genomes, additional pan-genome descriptions were compiled for the so-termed LF and EM genogroups. Open pan-genomes composed of 2,924 and 2,778 genes and core-genomes composed of 2,170 and 2,228 genes were respectively found for the LF and EM genogroups. The core-genomes were functionally annotated using the Gene Ontology, KEGG, and Virulence Factor databases, revealing the presence of several shared groups of genes related to basic function of intracellular survival and bacterial pathogenesis. Additionally, the specific pan-genomes for the LF and EM genogroups were defined, resulting in the identification of 148 and 273 exclusive proteins, respectively. Notably, specific virulence factors linked to adherence, colonization, invasion factors, and endotoxins were established. The obtained data suggest that these genes could be directly associated with inter-genogroup differences in pathogenesis and host-pathogen interactions, information that could be useful in designing novel strategies for diagnosing and controlling P. salmonis infection.

Comparative Pan-Genome Analysis of Piscirickettsia salmonis Reveals Genomic Divergences within Genogroups

PubMed Central

Nourdin-Galindo, Guillermo; Sánchez, Patricio; Molina, Cristian F.; Espinoza-Rojas, Daniela A.; Oliver, Cristian; Ruiz, Pamela; Vargas-Chacoff, Luis; Cárcamo, Juan G.; Figueroa, Jaime E.; Mancilla, Marcos; Maracaja-Coutinho, Vinicius; Yañez, Alejandro J.

2017-01-01

Piscirickettsia salmonis is the etiological agent of salmonid rickettsial septicemia, a disease that seriously affects the salmonid industry. Despite efforts to genomically characterize P. salmonis, functional information on the life cycle, pathogenesis mechanisms, diagnosis, treatment, and control of this fish pathogen remain lacking. To address this knowledge gap, the present study conducted an in silico pan-genome analysis of 19 P. salmonis strains from distinct geographic locations and genogroups. Results revealed an expected open pan-genome of 3,463 genes and a core-genome of 1,732 genes. Two marked genogroups were identified, as confirmed by phylogenetic and phylogenomic relationships to the LF-89 and EM-90 reference strains, as well as by assessments of genomic structures. Different structural configurations were found for the six identified copies of the ribosomal operon in the P. salmonis genome, indicating translocation throughout the genetic material. Chromosomal divergences in genomic localization and quantity of genetic cassettes were also found for the Dot/Icm type IVB secretion system. To determine divergences between core-genomes, additional pan-genome descriptions were compiled for the so-termed LF and EM genogroups. Open pan-genomes composed of 2,924 and 2,778 genes and core-genomes composed of 2,170 and 2,228 genes were respectively found for the LF and EM genogroups. The core-genomes were functionally annotated using the Gene Ontology, KEGG, and Virulence Factor databases, revealing the presence of several shared groups of genes related to basic function of intracellular survival and bacterial pathogenesis. Additionally, the specific pan-genomes for the LF and EM genogroups were defined, resulting in the identification of 148 and 273 exclusive proteins, respectively. Notably, specific virulence factors linked to adherence, colonization, invasion factors, and endotoxins were established. The obtained data suggest that these genes could be directly associated with inter-genogroup differences in pathogenesis and host-pathogen interactions, information that could be useful in designing novel strategies for diagnosing and controlling P. salmonis infection. PMID:29164068

Protein Secretion Systems in Pseudomonas aeruginosa: An Essay on Diversity, Evolution, and Function

PubMed Central

Filloux, Alain

2011-01-01

Protein secretion systems are molecular nanomachines used by Gram-negative bacteria to thrive within their environment. They are used to release enzymes that hydrolyze complex carbon sources into usable compounds, or to release proteins that capture essential ions such as iron. They are also used to colonize and survive within eukaryotic hosts, causing acute or chronic infections, subverting the host cell response and escaping the immune system. In this article, the opportunistic human pathogen Pseudomonas aeruginosa is used as a model to review the diversity of secretion systems that bacteria have evolved to achieve these goals. This diversity may result from a progressive transformation of cell envelope complexes that initially may not have been dedicated to secretion. The striking similarities between secretion systems and type IV pili, flagella, bacteriophage tail, or efflux pumps is a nice illustration of this evolution. Differences are also needed since various secretion configurations call for diversity. For example, some proteins are released in the extracellular medium while others are directly injected into the cytosol of eukaryotic cells. Some proteins are folded before being released and transit into the periplasm. Other proteins cross the whole cell envelope at once in an unfolded state. However, the secretion system requires conserved basic elements or features. For example, there is a need for an energy source or for an outer membrane channel. The structure of this review is thus quite unconventional. Instead of listing secretion types one after each other, it presents a melting pot of concepts indicating that secretion types are in constant evolution and use basic principles. In other words, emergence of new secretion systems could be predicted the way Mendeleïev had anticipated characteristics of yet unknown elements. PMID:21811488

Gemcitabine Hydrochloride and Docetaxel With or Without Bevacizumab in Treating Patients With Advanced or Recurrent Uterine Leiomyosarcoma

ClinicalTrials.gov

2017-07-13

Recurrent Uterine Corpus Sarcoma; Stage IIIA Uterine Sarcoma; Stage IIIB Uterine Sarcoma; Stage IIIC Uterine Sarcoma; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma; Uterine Corpus Leiomyosarcoma

Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer

ClinicalTrials.gov

2017-06-15

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

Radiation Therapy and Docetaxel in Treating Patients With HPV-Related Oropharyngeal Cancer

ClinicalTrials.gov

2017-11-14

Human Papillomavirus Infection; Stage I Oropharyngeal Squamous Cell Carcinoma; Stage II Oropharyngeal Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma

TAS102 in Combination With NAL-IRI in Advanced GI Cancers

ClinicalTrials.gov

2018-03-29

Colorectal Adenocarcinoma; Gastric Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Stage IV Colorectal Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer; Unresectable Pancreatic Carcinoma

20 CFR 638.515 - Recreation/avocational program.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Section 638.515 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.515 Recreation... procedures issued by the Job Corps Director. ...

20 CFR 638.504 - Occupational exploration program.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Section 638.504 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.504 Occupational... procedures issued by the Job Corps Director. ...

20 CFR 638.801 - Staff training.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Staff training. 638.801 Section 638.801... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.801 Staff training. The... office, and deliverer staff. ...

20 CFR 638.801 - Staff training.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Staff training. 638.801 Section 638.801... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.801 Staff training. The... office, and deliverer staff. ...

20 CFR 638.801 - Staff training.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Staff training. 638.801 Section 638.801... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.801 Staff training. The... office, and deliverer staff. ...

KSC-97PC1539

NASA Image and Video Library

1997-10-12

At Launch Complex 40 on Cape Canaveral Air Station, the Mobile Service Tower is rolled away from the Titan IVB/Centaur carrying the Cassini spacecraft, marking a major milestone in the launch countdown sequence. Retraction of the structure began about an hour later than scheduled due to minor problems with ground support equipment. The countdown clock for the Cassini mission began ticking earlier today at the T-26-hour mark. Other upcoming prelaunch milestones include activation of the final launch sequence for the Cassini spacecraft at the T-180-minute mark in the countdown, to be followed about an hour later by initiation of loading of the Titan IVB's Centaur stage with its complement of liquid hydrogen and liquid oxygen. Liftoff of Cassini on the journey to Saturn and its moon Titan is slated to occur during a window opening at 4:55 a.m. EDT, Oct. 13, and extending through 7:15 a.m

Titan 4B/Centaur/Cassini Service Tower Rollaway

NASA Technical Reports Server (NTRS)

1997-01-01

KENNEDY SPACE CENTER, FLA. -- At Launch Complex 40 on Cape Canaveral Air Station, the Mobile Service Tower is rolled away from the Titan IVB/Centaur carrying the Cassini spacecraft, marking a major milestone in the launch countdown sequence. Retraction of the structure began about an hour later than scheduled due to minor problems with ground support equipment. The countdown clock for the Cassini mission began ticking earlier today at the T-26-hour mark. Other upcoming prelaunch milestones include activation of the final launch sequence for the Cassini spacecraft at the T-180-minute mark in the countdown, to be followed about an hour later by initiation of loading of the Titan IVB's Centaur stage with its complement of liquid hydrogen and liquid oxygen. Liftoff of Cassini on the journey to Saturn and its moon Titan is slated to occur during a window opening at 4:55 a.m. EDT, Oct. 13, and extending through 7:15 a.m.

An immunohistochemical study of the endocrine pancreas in raptors.

PubMed

Palmieri, C; Shivaprasad, H L

2014-12-01

The cytoarchitecture of the endocrine pancreas of 10 raptors (golden eagles, peregrine falcons, Saker falcon, turkey vultures, red-tailed hawk and unspecified falcon) was examined by immunohistochemistry. Three islet types were identified: type A mixed islets composed mainly by glucagon (A)-secreting cells, type B mixed islets with predominantly insulin (B)-secreting cell component and type M mixed islets (type M) consisting of variable number of glucagon-, insulin- and somatostatin (D)-secreting cells. The latter were further characterized into Type I, II or III according to the cell distribution of the three cell types. A and D cells were also randomly scattered within the exocrine pancreas. The results of this study suggest that the classical concept in birds of a segregation of A and B cells in well-defined and distinct islets is not applicable in raptors, reflecting an evolutionary adaptation to different dietary habits and variation in developmental mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion.

PubMed

Knauf, Felix; Thomson, Robert B; Heneghan, John F; Jiang, Zhirong; Adebamiro, Adedotun; Thomson, Claire L; Barone, Christina; Asplin, John R; Egan, Marie E; Alper, Seth L; Aronson, Peter S

2017-01-01

Patients with cystic fibrosis have an increased incidence of hyperoxaluria and calcium oxalate nephrolithiasis. Net intestinal absorption of dietary oxalate results from passive paracellular oxalate absorption as modified by oxalate back secretion mediated by the SLC26A6 oxalate transporter. We used mice deficient in the cystic fibrosis transmembrane conductance regulator gene (Cftr) to test the hypothesis that SLC26A6-mediated oxalate secretion is defective in cystic fibrosis. We mounted isolated intestinal tissue from C57BL/6 (wild-type) and Cftr -/- mice in Ussing chambers and measured transcellular secretion of [ 14 C]oxalate. Intestinal tissue isolated from Cftr -/- mice exhibited significantly less transcellular oxalate secretion than intestinal tissue of wild-type mice. However, glucose absorption, another representative intestinal transport process, did not differ in Cftr -/- tissue. Compared with wild-type mice, Cftr -/- mice showed reduced expression of SLC26A6 in duodenum by immunofluorescence and Western blot analysis. Furthermore, coexpression of CFTR stimulated SLC26A6-mediated Cl - -oxalate exchange in Xenopus oocytes. In association with the profound defect in intestinal oxalate secretion, Cftr -/- mice had serum and urine oxalate levels 2.5-fold greater than those of wild-type mice. We conclude that defective intestinal oxalate secretion mediated by SLC26A6 may contribute to the hyperoxaluria observed in this mouse model of cystic fibrosis. Future studies are needed to address whether similar mechanisms contribute to the increased risk for calcium oxalate stone formation observed in patients with cystic fibrosis. Copyright © 2016 by the American Society of Nephrology.

Common and Distinct Capsid and Surface Protein Requirements for Secretion of Complete and Genome-free Hepatitis B Virions.

PubMed

Ning, Xiaojun; Luckenbaugh, Laurie; Liu, Kuancheng; Bruss, Volker; Sureau, Camille; Hu, Jianming

2018-05-09

During the morphogenesis of hepatitis B virus (HBV), an enveloped virus, two types of virions are secreted: (1) a minor population of complete virions containing a mature nucleocapsid with the characteristic, partially double-stranded, relaxed circular DNA genome and (2) a major population containing an empty capsid with no DNA or RNA (empty virions). Secretion of both types of virions requires interactions between the HBV capsid or core protein (HBc) and the viral surface or envelope proteins. We have studied the requirements from both HBc and envelope proteins for empty virion secretion, in comparison with those for secretion of complete virions. Substitutions within the N-terminal domain of HBc that block secretion of DNA-containing virions reduced but did not prevent secretion of empty virions. The HBc C-terminal domain was not essential for empty virion secretion. Among the three viral envelope proteins, the smallest, S, alone was sufficient for empty virion secretion at a basal level. The largest protein, L, essential for complete virion secretion, was not required for, but could stimulate empty virion secretion. Also, substitutions in L that eliminate secretion of complete virions reduced but did not eliminate empty virion secretion. S mutations that block secretion of the hepatitis D virus (HDV), an HBV satellite, did not block secretion of either empty or complete HBV virions. Together, these results indicate that both common and distinct signals on empty capsids vs. mature nucleocapsids interact with the S and L proteins during the formation of complete vs. empty virions. IMPORTANCE Hepatitis B virus (HBV) is a major cause of severe liver diseases including cirrhosis and cancer. In addition to the complete infectious virion particle, which contains an outer envelope layer and an interior capsid that, in turn, encloses a DNA genome, HBV infected cells also secrete non-infectious, incomplete viral particles in large excess over the complete virions. In particular, the empty (or genome-free) virion share with the complete virion the outer envelope and interior capsid but contain no genome. We have carried out a comparative study on the capsid and envelope requirements for the secretion of these two types of virion particles and uncovered both shared and distinct determinants on the capsid and envelope for their secretion. These results provide new information on HBV morphogenesis, and have implications for efforts to develop empty HBV virions as a novel biomarker and a new generation of HBV vaccine. Copyright © 2018 American Society for Microbiology.

Virulence of viral hemorrhagic septicemia virus (VHSV) genotypes Ia, IVa, IVb, and IVc in five fish species.

USGS Publications Warehouse

Emmenegger, Eveline J.; Moon, Chang Hoon; Hershberger, Paul K.; Kurath, Gael

2013-01-01

The susceptibility of yellow perch Perca flavescens, rainbow trout Oncorhynchus mykiss, Chinook salmon O. tshawytscha, koi Cyprinus carpio koi, and Pacific herring Clupea pallasii to 4 strains of viral hemorrhagic septicemia virus (VHSV) was assessed. Fish were challenged via intraperitoneal injection with high (1 × 106 plaque-forming units, PFU) and low (1 × 103 PFU) doses of a European strain (genotype Ia), and North American strains from the West coast (genotype IVa), Great Lakes (genotype IVb), and the East coast (genotype IVc). Pacific herring were exposed to the same VHSV strains, but at a single dose of 5 × 103 PFU ml-1 by immersion in static seawater. Overall, yellow perch were the most susceptible, with cumulative percent mortality (CPM) ranging from 84 to 100%, and 30 to 93% in fish injected with high or low doses of virus, respectively. Rainbow trout and Chinook salmon experienced higher mortalities (47 to 98% CPM) after exposure to strain Ia than to the other virus genotypes. Pacific herring were most susceptible to strain IVa with an average CPM of 80% and moderately susceptible (42 to 52% CPM) to the other genotypes. Koi had very low susceptibility (≤5.0% CPM) to all 4 VHSV strains. Fish tested at 7 d post challenge were positive for all virus strains, with yellow perch having the highest prevalence and concentrations of virus, and koi the lowest. While genotype Ia had higher virulence in salmonid species, there was little difference in virulence or host-specificity between isolates from subtypes IVa, IVb, and IVc.  

Stereotactic Body Radiation Therapy and Transarterial Chemoembolization in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-03-01

Child-Pugh Class A; Child-Pugh Class B; Stage IIIA Hepatocellular Carcinoma; Stage IIIB Hepatocellular Carcinoma; Stage IIIC Hepatocellular Carcinoma; Stage IVA Hepatocellular Carcinoma; Stage IVB Hepatocellular Carcinoma

20 CFR 638.522 - Evaluation of student progress.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Section 638.522 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.522 Evaluation of... issued by the Job Corps Director. ...

Family Caregiver Palliative Care Intervention in Supporting Caregivers of Patients With Stage II-IV Gastrointestinal, Gynecologic, Urologic and Lung Cancers

ClinicalTrials.gov

2018-02-12

Healthy Subject; Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Psychosocial Effects of Cancer and Its Treatment; Recurrent Bladder Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Gastric Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Recurrent Uterine Sarcoma; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage II Bladder Cancer; Stage II Renal Cell Cancer; Stage II Urethral Cancer; Stage IIA Cervical Cancer; Stage IIA Colon Cancer; Stage IIA Gastric Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIA Uterine Sarcoma; Stage IIB Cervical Cancer; Stage IIB Colon Cancer; Stage IIB Gastric Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIB Uterine Sarcoma; Stage IIC Colon Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Rectal Cancer; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage III Urethral Cancer; Stage IIIA Cervical Cancer; Stage IIIA Colon Cancer; Stage IIIA Gastric Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Uterine Sarcoma; Stage IIIB Cervical Cancer; Stage IIIB Colon Cancer; Stage IIIB Gastric Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Uterine Sarcoma; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC Uterine Sarcoma; Stage IV Bladder Cancer; Stage IV Gastric Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Renal Cell Cancer; Stage IV Urethral Cancer; Stage IVA Cervical Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVA Uterine Sarcoma; Stage IVB Cervical Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Stage IVB Uterine Sarcoma; Ureter Cancer; Stage IIA Lung Carcinoma; Stage IIB Lung Carcinoma; Stage IIIA Lung Carcinoma; Stage IIIB Lung Carcinoma

Effects of Psidium guajava leaf extract on secretion systems of Gram-negative enteropathogenic bacteria.

PubMed

Nakasone, Noboru; Ogura, Yasunori; Higa, Naomi; Toma, Claudia; Koizumi, Yukiko; Takaesu, Giichi; Suzuki, Toshihiko; Yamashiro, Tetsu

2018-05-23

We screened a total of 672 plant-tissue extracts to search for phytochemicals that inhibit the function of the type III secretion system (T3SS) of enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC). Among candidates examined, we found that an extract from the leaves of Psidium guajava (guava) inhibited the secretion of the EspB protein from EPEC and EHEC without affecting bacterial growth. The guava extract (GE) also inhibited EPEC and EHEC from adhering to and injecting EspB protein into HEp-2 cells. GE seemed to block the translocation of EspB from the bacterial cells to the culture medium. In addition to EPEC and EHEC, GE also inhibited the T3SS of Yersinia pseudotuberculosis and Salmonella enterica serovar Typhimurium. After exposure to GE, Y. pseudotuberculosis stopped the secretion of Yop proteins and lost its ability to induce the apoptosis of mouse bone marrow-derived macrophages. S. Typhimurium exposed to GE ceased the secretion of Sip proteins and lost its ability to invade HEp-2 cells. GE inhibited EspC secretion, the type V secretion protein of EPEC, but not Shiga toxin2 from EHEC. Thus, our results suggest that guava leaves contain a novel type of antimicrobial compound that could be used for the therapeutic treatment and prevention of gram-negative enteropathogenic bacterial infections. © 2018 The Societies and John Wiley & Sons Australia, Ltd.

Assembly of the Type II Secretion System such as Found in Vibrio cholerae Depends on the Novel Pilotin AspS

PubMed Central

Dunstan, Rhys A.; Heinz, Eva; Wijeyewickrema, Lakshmi C.; Pike, Robert N.; Purcell, Anthony W.; Evans, Timothy J.; Praszkier, Judyta; Robins-Browne, Roy M.; Strugnell, Richard A.; Korotkov, Konstantin V.; Lithgow, Trevor

2013-01-01

The Type II Secretion System (T2SS) is a molecular machine that drives the secretion of fully-folded protein substrates across the bacterial outer membrane. A key element in the machinery is the secretin: an integral, multimeric outer membrane protein that forms the secretion pore. We show that three distinct forms of T2SSs can be distinguished based on the sequence characteristics of their secretin pores. Detailed comparative analysis of two of these, the Klebsiella-type and Vibrio-type, showed them to be further distinguished by the pilotin that mediates their transport and assembly into the outer membrane. We have determined the crystal structure of the novel pilotin AspS from Vibrio cholerae, demonstrating convergent evolution wherein AspS is functionally equivalent and yet structurally unrelated to the pilotins found in Klebsiella and other bacteria. AspS binds to a specific targeting sequence in the Vibrio-type secretins, enhances the kinetics of secretin assembly, and homologs of AspS are found in all species of Vibrio as well those few strains of Escherichia and Shigella that have acquired a Vibrio-type T2SS. PMID:23326233

A reverse genetics system for the Great Lakes strain of viral hemorrhagic septicemia virus: the NV gene is required for pathogenicity

USGS Publications Warehouse

Ammayappan, Arun; Kurath, Gael; Thompson, Tarin M.; Vakharia, Vikram N.

2011-01-01

Viral hemorrhagic septicemia virus (VHSV), belonging to the genus Novirhabdovirus in the family of Rhabdoviridae, causes a highly contagious disease of fresh and saltwater fish worldwide. Recently, a novel genotype of VHSV, designated IVb, has invaded the Great Lakes in North America, causing large-scale epidemics in wild fish. An efficient reverse genetics system was developed to generate a recombinant VHSV of genotype IVb from cloned cDNA. The recombinant VHSV (rVHSV) was comparable to the parental wild-type strain both in vitro and in vivo, causing high mortality in yellow perch (Perca flavescens). A modified recombinant VHSV was generated in which the NV gene was substituted with an enhanced green fluorescent protein gene (rVHSV-ΔNV-EGFP), and another recombinant was made by inserting the EGFP gene into the full-length viral clone between the P and M genes (rVHSV-EGFP). The in vitro replication kinetics of rVHSV-EGFP was similar to rVHSV; however, the rVHSV-ΔNV-EGFP grew 2 logs lower. In yellow perch challenges, wtVHSV and rVHSV induced 82-100% cumulative per cent mortality (CPM), respectively, whereas rVHSV-EGFP produced 62% CPM and rVHSV-ΔNV-EGFP caused only 15% CPM. No reversion of mutation was detected in the recovered viruses and the recombinant viruses stably maintained the foreign gene after several passages. These results indicate that the NV gene of VHSV is not essential for viral replication in vitro and in vivo, but it plays an important role in viral replication efficiency and pathogenicity. This system will facilitate studies of VHSV replication, virulence, and production of viral vectored vaccines.

Analysis of the Listeria monocytogenes Population Structure among Isolates from 1931 to 2015 in Australia

PubMed Central

Jennison, Amy V.; Masson, Jesse J.; Fang, Ning-Xia; Graham, Rikki M.; Bradbury, Mark I.; Fegan, Narelle; Gobius, Kari S.; Graham, Trudy M.; Guglielmino, Christine J.; Brown, Janelle L.; Fox, Edward M.

2017-01-01

Listeriosis remains among the most important bacterial illnesses, with a high associated mortality rate. Efforts to control listeriosis require detailed knowledge of the epidemiology of the disease itself, and its etiological bacterium, Listeria monocytogenes. In this study we provide an in-depth analysis of the epidemiology of 224 L. monocytogenes isolates from Australian clinical and non-clinical sources. Non-human sources included meat, dairy, seafood, fruit, and vegetables, along with animal and environmental isolates. Serotyping, Multi-Locus Sequence Typing, and analysis of inlA gene sequence were performed. Serogroups IIA, IIB, and IVB comprised 94% of all isolates, with IVB over-represented among clinical isolates. Serogroup IIA was the most common among dairy and meat isolates. Lineage I isolates were most common among clinical isolates, and 52% of clinical isolates belonged to ST1. Overall 39 STs were identified in this study, with ST1 and ST3 containing the largest numbers of L. monocytogenes isolates. These STs comprised 40% of the total isolates (n = 90), and both harbored isolates from clinical and non-clinical sources. ST204 was the third most common ST. The high prevalence of this group among L. monocytogenes populations has not been reported outside Australia. Twenty-seven percent of the STs in this study contained exclusively clinical isolates. Analysis of the virulence protein InlA among isolates in this study identified a truncated form of the protein among isolates from ST121 and ST325. The ST325 group contained a previously unreported novel mutation leading to production of a 93 amino acid protein. This study provides insights in the population structure of L. monocytogenes isolated in Australia, which will contribute to public health knowledge relating to this important human pathogen. PMID:28428781

Characterization of Nops, nodulation outer proteins, secreted via the type III secretion system of NGR234.

PubMed

Marie, Corinne; Deakin, William J; Viprey, Virginie; Kopciñska, Joanna; Golinowski, Wladyslaw; Krishnan, Hari B; Perret, Xavier; Broughton, William J

2003-09-01

The nitrogen-fixing symbiotic bacterium Rhizobium species NGR234 secretes, via a type III secretion system (TTSS), proteins called Nops (nodulation outer proteins). Abolition of TTSS-dependent protein secretion has either no effect or leads to a change in the number of nodules on selected plants. More dramatically, Nops impair nodule development on Crotalaria juncea roots, resulting in the formation of nonfixing pseudonodules. A double mutation of nopX and nopL, which code for two previously identified secreted proteins, leads to a phenotype on Pachyrhizus tuberosus differing from that of a mutant in which the TTSS is not functional. Use of antibodies and a modification of the purification protocol revealed that NGR234 secretes additional proteins in a TTSS-dependent manner. One of them was identified as NopA, a small 7-kDa protein. Single mutations in nopX and nopL were also generated to assess the involvement of each Nop in protein secretion and nodule formation. Mutation of nopX had little effect on NopL and NopA secretion but greatly affected the interaction of NGR234 with many plant hosts tested. NopL was not necessary for the secretion of any Nops but was required for efficient nodulation of some plant species. NopL may thus act as an effector protein whose recognition is dependent upon the hosts' genetic background.

A translocator-specific export signal establishes the translocator-effector secretion hierarchy that is important for type III secretion system function

PubMed Central

Tomalka, Amanda G.; Stopford, Charles M.; Lee, Pei-Chung; Rietsch, Arne

2012-01-01

Summary Type III secretion systems are used by many Gram-negative pathogens to directly deliver effector proteins into the cytoplasm of host cells. To accomplish this, bacteria secrete translocator proteins that form a pore in the host-cell membrane through which the effector proteins are then introduced into the host cell. Evidence from multiple systems indicates that the pore-forming translocator proteins are exported before effectors, but how this secretion hierarchy is established is unclear. Here we used the P. aeruginosa translocator protein PopD as a model to identify its export signals. The amino-terminal secretion signal and chaperone, PcrH, are required for export under all conditions. Two novel signals in PopD, one proximal to the chaperone-binding site and one at the very C-terminus of the protein, are required for export of PopD before effector proteins. These novel export signals establish the translocator-effector secretion hierarchy, which in turn, is critical for the delivery of effectors into host cells. PMID:23121689

Role of the BK channel (KCa1.1) during activation of electrogenic K+ secretion in guinea pig distal colon

PubMed Central

Zhang, Jin; Halm, Susan T.

2012-01-01

Secretagogues acting at a variety of receptor types activate electrogenic K+ secretion in guinea pig distal colon, often accompanied by Cl− secretion. Distinct blockers of KCa1.1 (BK, Kcnma1), iberiotoxin (IbTx), and paxilline inhibited the negative short-circuit current (Isc) associated with K+ secretion. Mucosal addition of IbTx inhibited epinephrine-activated Isc (epiIsc) and transepithelial conductance (epiGt) consistent with K+ secretion occurring via apical membrane KCa1.1. The concentration dependence of IbTx inhibition of epiIsc yielded an IC50 of 193 nM, with a maximal inhibition of 51%. Similarly, IbTx inhibited epiGt with an IC50 of 220 nM and maximal inhibition of 48%. Mucosally added paxilline (10 μM) inhibited epiIsc and epiGt by ∼50%. IbTx and paxilline also inhibited Isc activated by mucosal ATP, supporting apical KCa1.1 as a requirement for this K+ secretagogue. Responses to IbTx and paxilline indicated that a component of K+ secretion occurred during activation of Cl− secretion by prostaglandin-E2 and cholinergic stimulation. Analysis of KCa1.1α mRNA expression in distal colonic epithelial cells indicated the presence of the ZERO splice variant and three splice variants for the COOH terminus. The presence of the regulatory β-subunits KCaβ1 and KCaβ4 also was demonstrated. Immunolocalization supported the presence of KCa1.1α in apical and basolateral membranes of surface and crypt cells. Together these results support a cellular mechanism for electrogenic K+ secretion involving apical membrane KCa1.1 during activation by several secretagogue types, but the observed K+ secretion likely required the activity of additional K+ channel types in the apical membrane. PMID:23064759

The New Kid on the Block: A Specialized Secretion System during Bacterial Sporulation.

PubMed

Morlot, Cécile; Rodrigues, Christopher D A

2018-02-02

The transport of proteins across the bacterial cell envelope is mediated by protein complexes called specialized secretion systems. These nanomachines exist in both Gram-positive and Gram-negative bacteria and have been categorized into different types based on their structural components and function. Interestingly, multiple studies suggest the existence of a protein complex in endospore-forming bacteria that appears to be a new type of specialized secretion system. This protein complex is called the SpoIIIA-SpoIIQ complex and is an exception to the categorical norm since it appears to be a hybrid composed of different parts from well-defined specialized secretion systems. Here we summarize and discuss the current understanding of this complex and its potential role as a specialized secretion system. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantitative analysis of the synthesis and secretion of type VII collagen in cultured human dermal fibroblasts with a sensitive sandwich enzyme-linked immunoassay.

PubMed

Amano, Satoshi; Ogura, Yuki; Akutsu, Nobuko; Nishiyama, Toshio

2007-02-01

Type VII collagen is the major component of anchoring fibrils in the epidermal basement membrane. Its expression has been analyzed by immunostaining or Northern blotting, but rarely at the protein level. In this study, we have quantitatively examined the effects of ascorbic acid and various cytokines/growth factors on the protein synthesis and secretion of type VII collagen by human dermal fibroblasts in culture, using a developed, highly sensitive sandwich enzyme-linked immunoassay with two kinds of specific monoclonal antibodies against the non-collagenous domain-1. Ascorbic acid and its derivative induced a twofold increase in type VII collagen synthesis, and markedly increased the secretion of type VII collagen into the medium when compared with the control culture. This effect was not influenced by the presence of transforming growth factor-beta1 (TGF-beta1). The synthesis of type VII collagen was elevated by TGF-beta1, platelet-derived growth factor, tumor necrosis factor-alpha, and interleukin-1beta, but not by TGF-alpha. Thus, our data indicate that the synthesis and secretion of type VII collagen in human dermal fibroblasts are regulated by ascorbate and the enhancement of type VII collagen gene expression by cytokines/growth factors is accompanied with elevated production of type VII collagen at the protein level.

A gatekeeper chaperone complex directs translocator secretion during Type Three Secretion

DOE PAGES

Archuleta, Tara L.; Spiller, Benjamin W.; Kubori, Tomoko

2014-11-06

Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver effector proteins into host cells. These protein delivery machines are composed of cytosolic components that recognize substrates and generate the force needed for translocation, the secretion conduit, formed by a needle complex and associated membrane spanning basal body, and translocators that form the pore in the target cell. A defined order of secretion in which needle component proteins are secreted first, followed by translocators, and finally effectors, is necessary for this system to be effective. While the secreted effectors vary significantly between organisms, the ~20 individual protein components thatmore » form the T3SS are conserved in many pathogenic bacteria. One such conserved protein, referred to as either a plug or gatekeeper, is necessary to prevent unregulated effector release and to allow efficient translocator secretion. The mechanism by which translocator secretion is promoted while effector release is inhibited by gatekeepers is unknown. We present the structure of the Chlamydial gatekeeper, CopN, bound to a translocator-specific chaperone. The structure identifies a previously unknown interface between gatekeepers and translocator chaperones and reveals that in the gatekeeper-chaperone complex the canonical translocator-binding groove is free to bind translocators. Thus, structure-based mutagenesis of the homologous complex in Shigella reveals that the gatekeeper-chaperone-translocator complex is essential for translocator secretion and for the ordered secretion of translocators prior to effectors.« less

Symbiotic implications of type III protein secretion machinery in Rhizobium.

PubMed

Viprey, V; Del Greco, A; Golinowski, W; Broughton, W J; Perret, X

1998-06-01

The symbiotic plasmid of Rhizobium sp. NGR234 carries a cluster of genes that encodes components of a bacterial type III secretion system (TTSS). In both animal and plant pathogens, the TTSS is an essential component of pathogenicity. Here, we show that secretion of at least two proteins (y4xL and NolX) is controlled by the TTSS of NGR234 and occurs after the induction with flavonoids. Polar mutations in two TTSS genes, rhcN and the nod-box controlled regulator of transcription y4xl, block the secretion of both proteins and strongly affect the ability of NGR234 to nodulate a variety of tropical legumes including Pachyrhizus tuberosus and Tephrosia vogelii.

The relationship between Type D personality and physical health complaints is mediated by perceived stress and anxiety but not diurnal cortisol secretion.

PubMed

Smith, Michael A; Riccalton, Victoria C; Kelly-Hughes, Denise H; Craw, Olivia A; Allen, Sarah F; O'Connor, Daryl B; Wetherell, Mark A

2018-05-01

Type D personality has been associated with minor health complaints in the general population and dysregulation of basal cortisol secretion in coronary patients. The aims of the present study were to investigate (i) whether there is an association between Type D personality and basal cortisol secretion in the general population, and (ii) whether subjective measures of stress and anxiety, as well as indices of basal cortisol secretion, mediate the relationship between Type D personality and self-reported physical symptoms in this group. Self-report measures of stress, trait anxiety and physical symptoms were provided by 101 individuals aged 18-45 years. Saliva samples were also provided over two consecutive "typical" days, to enable indices of the cortisol awakening response and diurnal cortisol profile to be determined. There was a significant relationship between Type D personality and self-reported physical symptoms, which was fully mediated by subjective stress and anxiety. However, there were no significant relationships between Type D personality and the basal cortisol indices. These findings suggest that the association between Type D personality and minor health complaints in the general population can be explained by feelings of stress and anxiety, but a precise biological mechanism for this link is yet to be elucidated.

Signaling from soybean roots to rhizobium: An ATP-binding cassette-type transporter mediates genistein secretion.

PubMed

Sugiyama, Akifumi; Shitan, Nobukazu; Yazaki, Kazufumi

2008-01-01

Legume plants have a unique ability to fix atmospheric nitrogen via symbiosis with rhizobia. For the establishment of symbiosis, legume plants secrete signaling molecules such as flavonoids from root tissues, leading to the attraction of rhizobia and the induction of rhizobial nod genes. Genistein and daidzein are found in soybean root exudates and function as signal molecules in soybean-Bradyrhizobium japonicum chemical communication. Although it is more than 20 years since these signal flavonoids were identified, almost nothing has been characterized concerning the membrane transport process of these molecules from soybean roots. To elucidate the transport mechanism we performed membrane transport assays with plasma membrane-enriched vesicles and various inhibitors. As a result, we concluded that an ATP-binding cassette-type transporter is involved in the secretion of genistein from soybean roots. The possible involvement of a pleiotropic drug resistance-type ABC transporter in this secretion is also discussed.

45 CFR 400.111 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Welfare Regulations Relating to Public Welfare OFFICE OF REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES REFUGEE RESETTLEMENT PROGRAM Child Welfare... of resettlement in its child welfare plan under title IV-B of the Social Security Act for the...

Sorafenib Tosylate and Pembrolizumab in Treating Patients With Advanced or Metastatic Liver Cancer

ClinicalTrials.gov

2018-06-04

Advanced Adult Hepatocellular Carcinoma; Child-Pugh Class A; Stage III Hepatocellular Carcinoma; Stage IIIA Hepatocellular Carcinoma; Stage IIIB Hepatocellular Carcinoma; Stage IIIC Hepatocellular Carcinoma; Stage IV Hepatocellular Carcinoma; Stage IVA Hepatocellular Carcinoma; Stage IVB Hepatocellular Carcinoma

Afatinib Dimaleate and Capecitabine in Treating Patients With Advanced Refractory Solid Tumors, Pancreatic Cancer or Biliary Cancer

ClinicalTrials.gov

2017-10-26

Advanced Malignant Solid Neoplasm; Bile Duct Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IVA Pancreatic Cancer; Stage IVB Pancreatic Cancer

Physical Activity Behavioral Intervention in Obese Endometrial Cancer Survivors

ClinicalTrials.gov

2015-10-14

Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Nivolumab in Treating Patients With Persistent, Recurrent, or Metastatic Cervical Cancer

ClinicalTrials.gov

2018-05-30

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Recurrent Cervical Carcinoma; Stage IV Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7

Ipilimumab in Treating Patients With Metastatic or Recurrent Human Papilloma Virus-Related Cervical Cancer

ClinicalTrials.gov

2018-05-23

Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Human Papillomavirus Infection; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7

Porous metallic bodies

DOEpatents

Landingham, R.L.

1984-03-13

Porous metallic bodies having a substantially uniform pore size of less than about 200 microns and a density of less than about 25 percent theoretical, as well as the method for making them, are disclosed. Group IIA, IIIB, IVB, VB, and rare earth metal hydrides a

77 FR 71198 - Environmental Assessment and Finding of No Significant Impact Related to Exemption From the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-29

... Levels for Hostile Action (10 CFR Part 50, App. E, IV.B.1.) Emergency Response Organization Augmentation... proposed action will not significantly impact the quality of the human environment, and that the proposed...

Rocket Impacts Recorded by the Apollo Seismic Network

NASA Image and Video Library

2010-03-22

On April 14th 1970, the Apollo 13 Saturn IVB upper stage impacted the Moon North of Mare Cognitum, at -2.55° latitude, -27.88° East longitude. This image was taken by NASA Lunar Reconnaissance Orbiter.

20 CFR 638.815 - Charging fees.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.815 Charging fees. No... in or to a training program under the Act. (Section 141(j)) ...

Doxorubicin Hydrochloride, Cisplatin, and Paclitaxel or Carboplatin and Paclitaxel in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer

ClinicalTrials.gov

2018-03-23

Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

A secretomics analysis reveals major differences in the macrophage responses towards different types of carbon nanotubes.

PubMed

Palomäki, Jaana; Sund, Jukka; Vippola, Minnamari; Kinaret, Pia; Greco, Dario; Savolainen, Kai; Puustinen, Anne; Alenius, Harri

2015-01-01

Certain types of carbon nanotubes (CNT) can evoke inflammation, fibrosis and mesothelioma in vivo, raising concerns about their potential health effects. It has been recently postulated that NLRP3 inflammasome activation is important in the CNT-induced toxicity. However, more comprehensive studies of the protein secretion induced by CNT can provide new information about their possible pathogenic mechanisms. Here, we studied protein secretion from human macrophages with a proteomic approach in an unbiased way. Human monocyte-derived macrophages (MDM) were exposed to tangled or rigid, long multi-walled CNT (MWCNT) or crocidolite asbestos for 6 h. The growth media was concentrated and secreted proteins were analyzed using 2D-DIGE and DeCyder software. Subsequently, significantly up- or down-regulated protein spots were in-gel digested and identified with an LC-MS/MS approach. Bioinformatics analysis was performed to reveal the different patterns of protein secretion induced by these materials. The results show that both long rigid MWCNT and asbestos elicited ample and highly similar protein secretion. In contrast, exposure to long tangled MWCNT induced weaker protein secretion with a more distinct profile. Secretion of lysosomal proteins followed the exposure to all materials, suggesting lysosomal damage. However, only long rigid MWCNT was associated with apoptosis. This analysis suggests that the CNT toxicity in human MDM is mediated via vigorous secretion of inflammation-related proteins and apoptosis. This study provides new insights into the mechanisms of toxicity of high aspect ratio nanomaterials and indicates that not all types of CNT are as hazardous as asbestos fibers.

Jamming dynamics of stretch-induced surfactant release by alveolar type II cells

PubMed Central

Majumdar, Arnab; Arold, Stephen P.; Bartolák-Suki, Erzsébet; Parameswaran, Harikrishnan

2012-01-01

Secretion of pulmonary surfactant by alveolar epithelial type II cells is vital for the reduction of interfacial surface tension, thus preventing lung collapse. To study secretion dynamics, rat alveolar epithelial type II cells were cultured on elastic membranes and cyclically stretched. The amounts of phosphatidylcholine, the primary lipid component of surfactant, inside and outside the cells, were measured using radiolabeled choline. During and immediately after stretch, cells secreted less surfactant than unstretched cells; however, stretched cells secreted significantly more surfactant than unstretched cells after an extended lag period. We developed a model based on the hypothesis that stretching leads to jamming of surfactant traffic escaping the cell, similar to vehicular traffic jams. In the model, stretch increases surfactant transport from the interior to the exterior of the cell. This transport is mediated by a surface layer with a finite capacity due to the limited number of fusion pores through which secretion occurs. When the amount of surfactant in the surface layer approaches this capacity, interference among lamellar bodies carrying surfactant reduces the rate of secretion, effectively creating a jam. When the stretch stops, the jam takes an extended time to clear, and subsequently the amount of secreted surfactant increases. We solved the model analytically and show that its dynamics are consistent with experimental observations, implying that surfactant secretion is a fundamentally nonlinear process with memory representing collective behavior at the level of single cells. Our results thus highlight the importance of a jamming dynamics in stretch-induced cellular secretory processes. PMID:22033531

The YopJ superfamily of type III efforts in plant-associated bacteria

USDA-ARS?s Scientific Manuscript database

Bacterial pathogens employ the type III secretion system to secrete and translocate effector proteins into their hosts. The primary function of these effector proteins is believed to be the suppression of host defense responses or innate immunity. However, some effector proteins may be recognized by...

Occult infection related hepatitis B surface antigen variants showing lowered secretion capacity

PubMed Central

Kim, Hong; Lee, Seoung-Ae; Won, You-Sub; Lee, HyunJoo; Kim, Bum-Joon

2015-01-01

AIM: To elucidate the molecular mechanisms underlying hepatitis B virus (HBV) occult infection of genotype C. METHODS: A total of 10 types of hepatitis B surface antigen (HBsAg) variants from a Korean occult cohort were used. After a complete HBV genome plasmid mutated such that it does not express HBsAg and plasmid encoding, each HBsAg variant was transiently co-transfected into HuH-7 cells. The secretion capacity and intracellular expression of the HBV virions and HBsAgs in their respective variants were analyzed using real-time quantitative polymerase chain reaction assays and commercial HBsAg enzyme-linked immunosorbent assays, respectively. RESULTS: All variants exhibited lower levels of HBsAg secretion into the medium compared with the wild type. In particular, in eight of the ten variants, very low levels of HBsAg secretion that were similar to the negative control were detected. In contrast, most variants (9/10) exhibited normal virion secretion capacities comparable with, or even higher than, the wild type. This provided new insight into the intrinsic nature of occult HBV infection, which leads to HBsAg sero-negativeness but has horizontal infectivity. Furthermore, most variants generated higher reactive oxidative species production than the wild type. This finding provides potential links between occult HBV infection and liver disease progression. CONCLUSION: The presently obtained data indicate that deficiency in the secretion capacity of HBsAg variants may have a pivotal function in the occult infections of HBV genotype C. PMID:25684944

Composition, formation, and regulation of the cytosolic c-ring, a dynamic component of the type III secretion injectisome.

PubMed

Diepold, Andreas; Kudryashev, Mikhail; Delalez, Nicolas J; Berry, Richard M; Armitage, Judith P

2015-01-01

Many gram-negative pathogens employ a type III secretion injectisome to translocate effector proteins into eukaryotic host cells. While the structure of the distal "needle complex" is well documented, the composition and role of the functionally important cytosolic complex remain less well understood. Using functional fluorescent fusions, we found that the C-ring, an essential and conserved cytosolic component of the system, is composed of ~22 copies of SctQ (YscQ in Yersinia enterocolitica), which require the presence of YscQC, the product of an internal translation initiation site in yscQ, for their cooperative assembly. Photoactivated localization microscopy (PALM) reveals that in vivo, YscQ is present in both a free-moving cytosolic and a stable injectisome-bound state. Notably, fluorescence recovery after photobleaching (FRAP) shows that YscQ exchanges between the injectisome and the cytosol, with a t½ of 68 ± 8 seconds when injectisomes are secreting. In contrast, the secretin SctC (YscC) and the major export apparatus component SctV (YscV) display minimal exchange. Under non-secreting conditions, the exchange rate of YscQ is reduced to t½ = 134 ± 16 seconds, revealing a correlation between C-ring exchange and injectisome activity, which indicates a possible role for C-ring stability in regulation of type III secretion. The stabilization of the C-ring depends on the presence of the functional ATPase SctN (YscN). These data provide new insights into the formation and composition of the injectisome and present a novel aspect of type III secretion, the exchange of C-ring subunits, which is regulated with respect to secretion.

The power of the patient question: A secret shopper study.

PubMed

Peters, Joanne; Desai, Karishma; Ricci, Daniel; Chen, Dan; Singh, Monny; Chewning, Betty

2016-09-01

To examine the effect of one standardized patient question on the length, number and type of new topics pharmacists addressed. To explore how community pharmacists counsel secret shoppers on two types of over-the-counter (OTC) medications-ibuprofen (IB) and emergency contraceptives (EC). 25 pharmacists from 7 independent, midwestern community pharmacies consented to have secret shoppers purchase an OTC medication and to have their consultations audio-recorded. Following standardized scenarios, 5 secret shoppers audio-recorded 73 encounters. At the end of 36 encounters secret shoppers asked one standard question, "What else should I know before taking this product?" Role Theory informed the study design with apriori hypotheses that topics assessed, topics discussed, and consultation length would vary by the OTC medication (IB or EC) and whether secret shoppers asked a question. Audio-recording coding had high inter-rater reliability (kappa=0.94). Length of encounter was significantly associated with patients asking the question (p<0.05), but not type of OTC medication. On average 1.22 new topics were discussed with a patient question. New topics included information about safe and efficacious use of the OTC's. Results highlight the importance of encouraging patients to ask pharmacists their questions about OTC products for safe use and thorough consultations. Copyright © 2016. Published by Elsevier Ireland Ltd.

Quercetin induces insulin secretion by direct activation of L-type calcium channels in pancreatic beta cells

PubMed Central

Bardy, G; Virsolvy, A; Quignard, J F; Ravier, M A; Bertrand, G; Dalle, S; Cros, G; Magous, R; Richard, S; Oiry, C

2013-01-01

Background and Purpose Quercetin is a natural polyphenolic flavonoid that displays anti-diabetic properties in vivo. Its mechanism of action on insulin-secreting beta cells is poorly documented. In this work, we have analysed the effects of quercetin both on insulin secretion and on the intracellular calcium concentration ([Ca2+]i) in beta cells, in the absence of any co-stimulating factor. Experimental Approach Experiments were performed on both INS-1 cell line and rat isolated pancreatic islets. Insulin release was quantified by the homogeneous time-resolved fluorescence method. Variations in [Ca2+]i were measured using the ratiometric fluorescent Ca2+ indicator Fura-2. Ca2+ channel currents were recorded with the whole-cell patch-clamp technique. Key Results Quercetin concentration-dependently increased insulin secretion and elevated [Ca2+]i. These effects were not modified by the SERCA inhibitor thapsigargin (1 μmol·L−1), but were nearly abolished by the L-type Ca2+ channel antagonist nifedipine (1 μmol·L−1). Similar to the L-type Ca2+ channel agonist Bay K 8644, quercetin enhanced the L-type Ca2+ current by shifting its voltage-dependent activation towards negative potentials, leading to the increase in [Ca2+]i and insulin secretion. The effects of quercetin were not inhibited in the presence of a maximally active concentration of Bay K 8644 (1 μmol·L−1), with the two drugs having cumulative effects on [Ca2+]i. Conclusions and Implications Taken together, our results show that quercetin stimulates insulin secretion by increasing Ca2+ influx through an interaction with L-type Ca2+ channels at a site different from that of Bay K 8644. These data contribute to a better understanding of quercetin's mechanism of action on insulin secretion. PMID:23530660

Semiquantum secret sharing using entangled states

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

Li Qin; Department of Computer Science, Sun Yat-sen University, Guangzhou 510006; Department of Mathematics, Hong Kong Baptist University, Kowloon

Secret sharing is a procedure for sharing a secret among a number of participants such that only the qualified subsets of participants have the ability to reconstruct the secret. Even in the presence of eavesdropping, secret sharing can be achieved when all the members are quantum. So what happens if not all the members are quantum? In this paper, we propose two semiquantum secret sharing protocols by using maximally entangled Greenberger-Horne-Zeilinger-type states in which quantum Alice shares a secret with two classical parties, Bob and Charlie, in a way that both parties are sufficient to obtain the secret, but onemore » of them cannot. The presented protocols are also shown to be secure against eavesdropping.« less

PF-4/CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion.

PubMed

Lasagni, Laura; Grepin, Renaud; Mazzinghi, Benedetta; Lazzeri, Elena; Meini, Claudia; Sagrinati, Costanza; Liotta, Francesco; Frosali, Francesca; Ronconi, Elisa; Alain-Courtois, Nathalie; Ballerini, Lara; Netti, Giuseppe Stefano; Maggi, Enrico; Annunziato, Francesco; Serio, Mario; Romagnani, Sergio; Bikfalvi, Andreas; Romagnani, Paola

2007-05-15

PF-4/CXCL4 is a member of the CXC chemokine family, which is mainly produced by platelets and known for its pleiotropic biological functions. Recently, the proteic product of a nonallelic variant gene of CXCL4 was isolated from human platelets and named as CXCL4L1. CXCL4L1 shows only 4.3% amino acid divergence in the mature protein, but exhibits a 38% amino acid divergence in the signal peptide region. We hypothesized that this may imply a difference in the cell type in which CXCL4L1 is expressed or a difference in its mode of secretion. In different types of transfected cells, CXCL4 and CXCL4L1 exhibited a distinct subcellular localization and a differential regulation of secretion, CXCL4 being stored in secretory granules and released in response to protein kinase C activation, whereas CXCL4L1 was continuously synthesized and secreted through a constitutive pathway. A protein kinase C-regulated CXCL4 secretion was observed also in lymphocytes, a cell type expressing mainly CXCL4 mRNA, whereas smooth muscle cells, which preferentially expressed CXCL4L1, exhibited a constitutive pathway of secretion. These results demonstrate that CXCL4 and CXCL4L1 exhibit a distinct subcellular localization and are secreted in a differentially regulated manner, suggesting distinct roles in inflammatory or homeostatic processes.

Regulation of Cl(-) secretion by AMPK in vivo.

PubMed

Kongsuphol, Patthara; Hieke, Bernhard; Ousingsawat, Jiraporn; Almaca, Joana; Viollet, Benoit; Schreiber, Rainer; Kunzelmann, Karl

2009-03-01

Previous in vitro studies suggested that Cl(-) currents produced by the cystic fibrosis transmembrane conductance regulator (CFTR; ABCC7) are inhibited by the alpha1 isoform of the adenosine monophosphate (AMP)-stimulated kinase (AMPK). AMPK is a serine/threonine kinase that is activated during metabolic stress. It has been proposed as a potential mediator for transport-metabolism coupling in epithelial tissues. All previous studies have been performed in vitro and thus little is known about the regulation of Cl(-) secretion by AMPK in vivo. Using AMPKalpha1(-/-) mice and wild-type littermates, we demonstrate that phenformin, an activator of AMPK, strongly inhibits cAMP-activated Cl(-) secretion in mouse airways and colon, when examined in ex vivo in Ussing chamber recordings. However, phenformin was equally effective in AMPKalpha1(-/-) and wild-type animals, suggesting additional AMPK-independent action of phenformin. Phenformin inhibited CFTR Cl(-) conductance in basolaterally permeabilized colonic epithelium from AMPKalpha1(+/+) but not AMPKalpha1(-/-) mice. The inhibitor of AMPK compound C enhanced CFTR-mediated Cl(-) secretion in epithelial tissues of AMPKalpha1(-/-) mice, but not in wild-type littermates. There was no effect on Ca(2+)-mediated Cl(-) secretion, activated by adenosine triphosphate or carbachol. Moreover CFTR-dependent Cl(-) secretion was enhanced in the colon of AMPKalpha1(-/-) mice, as indicated in Ussing chamber ex vivo and rectal PD measurements in vivo. Taken together, these data suggest that epithelial Cl(-) secretion mediated by CFTR is controlled by AMPK in vivo.

Gene and transcript abundances of bacterial type III secretion systems from the rumen microbiome are correlated with methane yield in sheep.

PubMed

Kamke, Janine; Soni, Priya; Li, Yang; Ganesh, Siva; Kelly, William J; Leahy, Sinead C; Shi, Weibing; Froula, Jeff; Rubin, Edward M; Attwood, Graeme T

2017-08-08

Ruminants are important contributors to global methane emissions via microbial fermentation in their reticulo-rumens. This study is part of a larger program, characterising the rumen microbiomes of sheep which vary naturally in methane yield (g CH 4 /kg DM/day) and aims to define differences in microbial communities, and in gene and transcript abundances that can explain the animal methane phenotype. Rumen microbiome metagenomic and metatranscriptomic data were analysed by Gene Set Enrichment, sparse partial least squares regression and the Wilcoxon Rank Sum test to estimate correlations between specific KEGG bacterial pathways/genes and high methane yield in sheep. KEGG genes enriched in high methane yield sheep were reassembled from raw reads and existing contigs and analysed by MEGAN to predict their phylogenetic origin. Protein coding sequences from Succinivibrio dextrinosolvens strains were analysed using Effective DB to predict bacterial type III secreted proteins. The effect of S. dextrinosolvens strain H5 growth on methane formation by rumen methanogens was explored using co-cultures. Detailed analysis of the rumen microbiomes of high methane yield sheep shows that gene and transcript abundances of bacterial type III secretion system genes are positively correlated with methane yield in sheep. Most of the bacterial type III secretion system genes could not be assigned to a particular bacterial group, but several genes were affiliated with the genus Succinivibrio, and searches of bacterial genome sequences found that strains of S. dextrinosolvens were part of a small group of rumen bacteria that encode this type of secretion system. In co-culture experiments, S. dextrinosolvens strain H5 showed a growth-enhancing effect on a methanogen belonging to the order Methanomassiliicoccales, and inhibition of a representative of the Methanobrevibacter gottschalkii clade. This is the first report of bacterial type III secretion system genes being associated with high methane emissions in ruminants, and identifies these secretions systems as potential new targets for methane mitigation research. The effects of S. dextrinosolvens on the growth of rumen methanogens in co-cultures indicate that bacteria-methanogen interactions are important modulators of methane production in ruminant animals.

KSC-69-h-960

NASA Image and Video Library

1969-07-06

The astronauts enter the spacecraft. After launch and Saturn V first-stage burnout and jettison, the S-II second stage ignites. The crew checks spacecraft systems in Earth orbit before the S-IVB third stage ignites the second time to send Apollo 11 to the Moon

Cabozantinib-s-malate in Treating Patients With Relapsed Osteosarcoma or Ewing Sarcoma

ClinicalTrials.gov

2018-05-23

Metastatic Ewing Sarcoma; Metastatic Osteosarcoma; Recurrent Ewing Sarcoma; Recurrent Osteosarcoma; Stage III Osteosarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Unresectable Ewing Sarcoma; Unresectable Osteosarcoma

Around Marshall

NASA Image and Video Library

1968-02-22

During a visit to the Marshall Space Flight Center (MSFC), the Congressional House Committee on Science and Astronautics toured the S-IVB workshop. Pictured here are MSFC’s Dr. Wernher von Braun (standing) and Congressman Miller, Democratic representative of California (sitting on the ergometer bicycle) inside the workshop.

TAS-102 in Treating Advanced Biliary Tract Cancers

ClinicalTrials.gov

2017-10-23

Cholangiocarcinoma; Stage III Gallbladder Cancer AJCC v7; Stage IIIA Gallbladder Cancer AJCC v7; Stage IIIB Gallbladder Cancer AJCC v7; Stage IV Gallbladder Cancer AJCC v7; Stage IVA Gallbladder Cancer AJCC v7; Stage IVB Gallbladder Cancer AJCC v7

20 CFR 638.803 - Safety.

Code of Federal Regulations, 2010 CFR

2010-04-01

...' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.803 Safety. (a) The Job Corps... unsanitary, hazardous, or lack proper ventilation. Whenever students are employed or trained for jobs, they...

20 CFR 638.501 - Student handbook.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.501 Student handbook. Each center... to all students in accordance with procedures issued by the Job Corps Director. ...

20 CFR 638.811 - Review and evaluation.

Code of Federal Regulations, 2010 CFR

2010-04-01

....811 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.811 Review and evaluation. The Job Corps Director shall establish adequate program management to provide continuous...

20 CFR 638.813 - Nondiscrimination; nonsectarian activities.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... 638.813 Section 638.813 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions... assistance. (Section 167) (b) Nonsectarian activities. Students shall not be employed or trained on the...

20 CFR 638.810 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

....810 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.810 Reporting requirements. The Job Corps Director shall establish procedures to ensure timely and complete reporting of such...

26 CFR 1.334-1 - Basis of property received in liquidations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... partial or complete liquidation and if gain or loss is recognized on the receipt of such property, then... transfer to which section 332(c) is applicable. See § 1.460-4(k)(3)(iv)(B)(2) for rules relating to...

26 CFR 1.334-1 - Basis of property received in liquidations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... partial or complete liquidation and if gain or loss is recognized on the receipt of such property, then... transfer to which section 332(c) is applicable. See § 1.460-4(k)(3)(iv)(B)(2) for rules relating to...

26 CFR 1.334-1 - Basis of property received in liquidations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... partial or complete liquidation and if gain or loss is recognized on the receipt of such property, then... transfer to which section 332(c) is applicable. See § 1.460-4(k)(3)(iv)(B)(2) for rules relating to...

Identification of the Vibrio parahaemolyticus type III secretion system 2-associated chaperone VocC for the T3SS2-specific effector VopC.

PubMed

Akeda, Yukihiro; Kodama, Toshio; Saito, Kazunobu; Iida, Tetsuya; Oishi, Kazunori; Honda, Takeshi

2011-11-01

The enteropathogen Vibrio parahaemolyticus possesses two sets of type III secretion systems, T3SS1 and T3SS2. Effector proteins secreted by these T3SSs are delivered into host cells, leading to cell death or diarrhea. However, it is not known how specific effectors are secreted through a specific T3SS when both T3SSs are expressed within bacteria. One molecule thought to determine secretion specificity is a T3SS-associated chaperone; however, no T3SS2-specific chaperone has been identified. Therefore, we screened T3SS2 chaperone candidates by a pull-down assay using T3SS2 effectors fused with glutathione-S-transferase. A secretion assay revealed that the newly identified cognate chaperone VocC for the T3SS2-specific effector VopC was required for the efficient secretion of the substrate through T3SS2. Further experiments determined the chaperone-binding domain and the amino-terminal secretion signal of the cognate effector. These findings, in addition to the previously identified T3SS1-specific chaperone, VecA, provide a strategy to clarify the specificity of effector secretion through T3SSs of V. parahaemolyticus. 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

DsbA Plays a Critical and Multifaceted Role in the Production of Secreted Virulence Factors by the Phytopathogen Erwinia carotovora subsp. atroseptica*S⃞

PubMed Central

Coulthurst, Sarah J.; Lilley, Kathryn S.; Hedley, Peter E.; Liu, Hui; Toth, Ian K.; Salmond, George P. C.

2008-01-01

Erwinia carotovora subsp. atroseptica is an enterobacterial phytopathogen causing economically significant soft rot disease. Pathogenesis is mediated by multiple secreted virulence factors, many of which are secreted by the type II (Out) secretion system. DsbA catalyzes the introduction of disulfide bonds into periplasmic and secreted proteins. In this study, the extracellular proteome (secretome) of wild type E. carotovora subsp. atroseptica SCRI1043, and dsbA and out mutants, was analyzed by spectral counting mass spectrometry. This revealed that dsbA inactivation had a huge impact on the secretome and identified diverse DsbA- and Out-dependent secreted proteins, representing known, predicted, and novel candidate virulence factors. Further characterization of the dsbA mutant showed that secreted enzyme activities, motility, production of the quorumsensing signal, and virulence were absent or substantially reduced. The impact of DsbA on secreted virulence factor production was mediated at multiple levels, including impacting on the Out secretion system and the virulence gene regulatory network. Transcriptome analyses revealed that the abundance of a broad, but defined, set of transcripts, including many virulence factors, was altered in the dsbA mutant, identifying a new virulence regulon responsive to extracytoplasmic conditions. In conclusion, DsbA plays a crucial, multifaceted role in the pathogenesis of E. carotovora subsp. atroseptica. PMID:18562317

Autoproteolysis and Intramolecular Dissociation of Yersinia YscU Precedes Secretion of Its C-Terminal Polypeptide YscUCC

PubMed Central

Frost, Stefan; Ho, Oanh; Login, Frédéric H.; Weise, Christoph F.; Wolf-Watz, Hans; Wolf-Watz, Magnus

2012-01-01

Type III secretion system mediated secretion and translocation of Yop-effector proteins across the eukaryotic target cell membrane by pathogenic Yersinia is highly organized and is dependent on a switching event from secretion of early structural substrates to late effector substrates (Yops). Substrate switching can be mimicked in vitro by modulating the calcium levels in the growth medium. YscU that is essential for regulation of this switch undergoes autoproteolysis at a conserved N↑PTH motif, resulting in a 10 kDa C-terminal polypeptide fragment denoted YscUCC. Here we show that depletion of calcium induces intramolecular dissociation of YscUCC from YscU followed by secretion of the YscUCC polypeptide. Thus, YscUCC behaved in vivo as a Yop protein with respect to secretion properties. Further, destabilized yscU mutants displayed increased rates of dissociation of YscUCC in vitro resulting in enhanced Yop secretion in vivo at 30°C relative to the wild-type strain.These findings provide strong support to the relevance of YscUCC dissociation for Yop secretion. We propose that YscUCC orchestrates a block in the secretion channel that is eliminated by calcium depletion. Further, the striking homology between different members of the YscU/FlhB family suggests that this protein family possess regulatory functions also in other bacteria using comparable mechanisms. PMID:23185318

Autoproteolysis and intramolecular dissociation of Yersinia YscU precedes secretion of its C-terminal polypeptide YscU(CC).

PubMed

Frost, Stefan; Ho, Oanh; Login, Frédéric H; Weise, Christoph F; Wolf-Watz, Hans; Wolf-Watz, Magnus

2012-01-01

Type III secretion system mediated secretion and translocation of Yop-effector proteins across the eukaryotic target cell membrane by pathogenic Yersinia is highly organized and is dependent on a switching event from secretion of early structural substrates to late effector substrates (Yops). Substrate switching can be mimicked in vitro by modulating the calcium levels in the growth medium. YscU that is essential for regulation of this switch undergoes autoproteolysis at a conserved N↑PTH motif, resulting in a 10 kDa C-terminal polypeptide fragment denoted YscU(CC). Here we show that depletion of calcium induces intramolecular dissociation of YscU(CC) from YscU followed by secretion of the YscU(CC) polypeptide. Thus, YscU(CC) behaved in vivo as a Yop protein with respect to secretion properties. Further, destabilized yscU mutants displayed increased rates of dissociation of YscU(CC)in vitro resulting in enhanced Yop secretion in vivo at 30°C relative to the wild-type strain.These findings provide strong support to the relevance of YscU(CC) dissociation for Yop secretion. We propose that YscU(CC) orchestrates a block in the secretion channel that is eliminated by calcium depletion. Further, the striking homology between different members of the YscU/FlhB family suggests that this protein family possess regulatory functions also in other bacteria using comparable mechanisms.

Campylobacter fetus subspecies contain conserved type IV secretion systems on multiple genomic islands and plasmids

USDA-ARS?s Scientific Manuscript database

The features contributing to the differences in pathogenicity of the C. fetus subspecies are unknown. Putative factors involved in pathogenesis are located in genomic islands that encode type IV secretion system (T4SS) and fic-domain (filamentation induced by cyclic AMP) proteins. In the genomes of ...

The Efficacy of Intravitreal Bevacizumab in Vitreous Hemorrhage of Diabetic Subjects

PubMed Central

Alagöz, Cengiz; Yıldırım, Yusuf; Kocamaz, Murat; Baz, Ökkeş; Çiçek, Uğur; Çelik, Burcu; Demirkale, Halil İbrahim; Yazıcı, Ahmet Taylan; Taşkapılı, Muhittin

2016-01-01

Objectives: To evaluate the efficacy of intravitreal bevacizumab (IVB) in the resolution of vitreous hemorrhage (VH) secondary to proliferative diabetic retinopathy (PDR). Materials and Methods: Seventy eyes of 70 patients (43 male, mean age 55.6±12.2 years) diagnosed with VH secondary to PDR were evaluated retrospectively. Demographic characteristics of the patients, baseline and final clinical results, and the interventions the patients were subject to were recorded. The patients who received IVB injections (group 1, n=29) were compared to those who did not receive injections (group 2, n=41) in terms of VH clearance time and surgery rates. Results: The mean follow-up time was 14.5±6.1 months in group 1 and 18.4±9.6 months in group 2 (p=0.185). The mean visual acuity was similar between the groups at baseline and at the last visit (for all p>0.05). Panretinal photocoagulation could be applied in 86% of subjects in group 1 and in 58% in group 2 2 within the first month (p=0.016). VH clearance time was not different between the groups (2.3±2.1 months in group 1 and 3.4±2.6 months in group 2, p=0.146). The number of subjects requiring surgery was 7 (24%) in group 1 and 20 (48.8%) in group 2 (p=0.048). Conclusion: IVB was found effective in cases with VH secondary to PDR in terms of reducing the need for surgery and increasing the rate of subjects to whom panretinal photocoagulation could be applied in the early period, although there was no impact on final visual acuity. PMID:28058164

Ropidoxuridine in Treating Patients With Advanced Gastrointestinal Cancer Undergoing Radiation Therapy

ClinicalTrials.gov

2018-03-02

Advanced Bile Duct Carcinoma; Stage II Esophageal Cancer AJCC v7; Stage II Pancreatic Cancer AJCC v6 and v7; Stage IIA Esophageal Cancer AJCC v7; Stage IIA Pancreatic Cancer AJCC v6 and v7; Stage IIB Esophageal Cancer AJCC v7; Stage IIB Pancreatic Cancer AJCC v6 and v7; Stage III Colon Cancer AJCC v7; Stage III Esophageal Cancer AJCC v7; Stage III Gastric Cancer AJCC v7; Stage III Liver Cancer; Stage III Pancreatic Cancer AJCC v6 and v7; Stage III Rectal Cancer AJCC v7; Stage III Small Intestinal Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIA Esophageal Cancer AJCC v7; Stage IIIA Gastric Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIA Small Intestinal Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIB Esophageal Cancer AJCC v7; Stage IIIB Gastric Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIB Small Intestinal Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7; Stage IIIC Esophageal Cancer AJCC v7; Stage IIIC Gastric Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Colon Cancer AJCC v7; Stage IV Esophageal Cancer AJCC v7; Stage IV Gastric Cancer AJCC v7; Stage IV Liver Cancer; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IV Rectal Cancer AJCC v7; Stage IV Small Intestinal Cancer AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Liver Cancer; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Liver Cancer; Stage IVB Rectal Cancer AJCC v7

Curative Chemoradiotherapy in Patients With Stage IVB Cervical Cancer Presenting With Paraortic and Left Supraclavicular Lymph Node Metastases

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

Kim, Ji-Yoon; Kim, Joo-Young; Kim, Jin Hee

2012-11-01

Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with curative intent in patients with stage IVB cervical cancer initially presenting with paraortic and left supraclavicular lymph node metastases. Methods and Materials: The medical records of 25 patients with both paraortic and left supraclavicular lymph nodal metastases (group I) were reviewed and compared with those of 101 women with paraortic lymph node metastases alone (group II). Group I received a mean 59.4 Gy to the paraortic and left supraclavicular areas and 50.4 Gy to the pelvis, followed by 30 Gy of high-dose-rate brachytherapy in 6 fractions. Group IImore » received the same dose to the paraortic area and pelvis followed by intracavitary brachytherapy. All patients received platinum-based chemotherapy simultaneously. Results: Of the 25 patients in group I, 16 (64%) experienced acute grade 3-4 hematologic toxicities, and 1 had a late grade 3 genitourinary toxicity. Complete responses, including the primary mass and pelvic, paraortic, and left supraclavicular lymph nodes, were observed in 13 patients (52%). At a median follow-up of 32 months for surviving patients, 3 experienced in-field failure, 6 showed distant failure, and 9 showed both. The 3-year overall and disease-free survival rates were 49% and 33%, respectively. In comparison, of the 101 patients in group II, 16 showed in-field failure, 14 experienced distant failure, and 11 showed both. The 3-year overall and disease-free survival rates were 69% and 57%, respectively. Conclusions: Curative CCRT is feasible in patients with stage IVB cervical cancer presenting with paraortic and left supraclavicular lymph nodal metastases, with acceptable late toxicity and high response rates, despite high rates of acute hematologic toxicity.« less

Health Care Coach Support in Reducing Acute Care Use and Cost in Patients With Cancer

ClinicalTrials.gov

2017-05-12

Acute Myeloid Leukemia; Brain Glioblastoma; Estrogen Receptor Negative; Extensive Stage Small Cell Lung Carcinoma; Head and Neck Carcinoma; HER2/Neu Negative; Hormone-Resistant Prostate Cancer; Limited Stage Small Cell Lung Carcinoma; Myelodysplastic Syndrome; Progesterone Receptor Negative; Progressive Disease; Recurrent Carcinoma; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage III Colon Cancer; Stage III Esophageal Cancer; Stage III Gastric Cancer; Stage III Non-Small Cell Lung Cancer; Stage III Ovarian Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Skin Melanoma; Stage IIIA Colon Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Rectal Cancer; Stage IIIA Skin Melanoma; Stage IIIB Colon Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Rectal Cancer; Stage IIIB Skin Melanoma; Stage IIIC Colon Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Rectal Cancer; Stage IIIC Skin Melanoma; Stage IV Bladder Cancer; Stage IV Bone Sarcoma; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IV Soft Tissue Sarcoma; Stage IVA Bone Sarcoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Bone Sarcoma; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Triple-Negative Breast Carcinoma

Colleters in Rubiaceae from forest and savanna: the link between secretion and environment

NASA Astrophysics Data System (ADS)

Tresmondi, Fernanda; Canaveze, Yve; Guimarães, Elza; Machado, Silvia Rodrigues

2017-04-01

This study aims to investigate colleters' secretory function, on cellular level, in Rubiaceae species from contrasting environments looking to explore the association between secretion and environment. We collected samples from eight species of Rubiaceae growing in forest and savanna having standard-type colleters with diverse histochemistry (hydrophilic, lipophilic and mixed secretions) and processed for both conventional and cytochemical study under transmission electron microscopy (TEM). The standard colleters, although similar in morphology and anatomy, exhibited marked differences on cellular level, especially in the abundance and topology of Golgi bodies, endoplasmic reticulum and plastids when comparing forest and savanna species. These differences were clearly aligned with the chemical nature of the secretions they produce, with predominance of hydrophilic secretions in forest species and lipophilic or mixed secretions in savanna species. The combination of methods in electron microscopy revealed the sites of synthesis and intracellular compartmentation of substances, the mechanisms of their secretion from the protoplast and confirmed the involvement of the outer walls of the epithelial cells in the elimination of exudates to the gland surface. Our study suggests a potential environment-associated plasticity of the secretory cells of standard-type colleters in modulating their secretory function performance.

Deficiency of Starch Synthase IIIa and IVb Alters Starch Granule Morphology from Polyhedral to Spherical in Rice Endosperm1

PubMed Central

Toyosawa, Yoshiko; Kawagoe, Yasushi; Matsushima, Ryo; Ogawa, Masahiro; Fukuda, Masako; Kumamaru, Toshihiro; Okazaki, Yozo; Kusano, Miyako; Saito, Kazuki; Toyooka, Kiminori; Sato, Mayuko; Ai, Yongfeng; Fujita, Naoko

2016-01-01

Starch granule morphology differs markedly among plant species. However, the mechanisms controlling starch granule morphology have not been elucidated. Rice (Oryza sativa) endosperm produces characteristic compound-type granules containing dozens of polyhedral starch granules within an amyloplast. Some other cereal species produce simple-type granules, in which only one starch granule is present per amyloplast. A double mutant rice deficient in the starch synthase (SS) genes SSIIIa and SSIVb (ss3a ss4b) produced spherical starch granules, whereas the parental single mutants produced polyhedral starch granules similar to the wild type. The ss3a ss4b amyloplasts contained compound-type starch granules during early developmental stages, and spherical granules were separated from each other during subsequent amyloplast development and seed dehydration. Analysis of glucan chain length distribution identified overlapping roles for SSIIIa and SSIVb in amylopectin chain synthesis, with a degree of polymerization of 42 or greater. Confocal fluorescence microscopy and immunoelectron microscopy of wild-type developing rice seeds revealed that the majority of SSIVb was localized between starch granules. Therefore, we propose that SSIIIa and SSIVb have crucial roles in determining starch granule morphology and in maintaining the amyloplast envelope structure. We present a model of spherical starch granule production. PMID:26747287

IL-6-Type Cytokine Signaling in Adipocytes Induces Intestinal GLP-1 Secretion.

PubMed

Wueest, Stephan; Laesser, Céline I; Böni-Schnetzler, Marianne; Item, Flurin; Lucchini, Fabrizio C; Borsigova, Marcela; Müller, Werner; Donath, Marc Y; Konrad, Daniel

2018-01-01

We recently showed that interleukin (IL)-6-type cytokine signaling in adipocytes induces free fatty acid release from visceral adipocytes, thereby promoting obesity-induced hepatic insulin resistance and steatosis. In addition, IL-6-type cytokines may increase the release of leptin from adipocytes and by those means induce glucagon-like peptide 1 (GLP-1) secretion. We thus hypothesized that IL-6-type cytokine signaling in adipocytes may regulate insulin secretion. To this end, mice with adipocyte-specific knockout of gp130, the signal transducer protein of IL-6, were fed a high-fat diet for 12 weeks. Compared with control littermates, knockout mice showed impaired glucose tolerance and circulating leptin, GLP-1, and insulin levels were reduced. In line, leptin release from isolated adipocytes was reduced, and intestinal proprotein convertase subtilisin/kexin type 1 ( Pcsk1 ) expression, the gene encoding PC1/3, which controls GLP-1 production, was decreased in knockout mice. Importantly, treatment with the GLP-1 receptor antagonist exendin 9-39 abolished the observed difference in glucose tolerance between control and knockout mice. Ex vivo, supernatant collected from isolated adipocytes of gp130 knockout mice blunted Pcsk1 expression and GLP-1 release from GLUTag cells. In contrast, glucose- and GLP-1-stimulated insulin secretion was not affected in islets of knockout mice. In conclusion, adipocyte-specific IL-6 signaling induces intestinal GLP-1 release to enhance insulin secretion, thereby counteracting insulin resistance in obesity. © 2017 by the American Diabetes Association.

Norepinephrine is coreleased with serotonin in mouse taste buds.

PubMed

Huang, Yijen A; Maruyama, Yutaka; Roper, Stephen D

2008-12-03

ATP and serotonin (5-HT) are neurotransmitters secreted from taste bud receptor (type II) and presynaptic (type III) cells, respectively. Norepinephrine (NE) has also been proposed to be a neurotransmitter or paracrine hormone in taste buds. Yet, to date, the specific stimulus for NE release in taste buds is not well understood, and the identity of the taste cells that secrete NE is not known. Chinese hamster ovary cells were transfected with alpha(1A) adrenoceptors and loaded with fura-2 ("biosensors") to detect NE secreted from isolated mouse taste buds and taste cells. Biosensors responded to low concentrations of NE (>or=10 nm) with a reliable fura-2 signal. NE biosensors did not respond to stimulation with KCl or taste compounds. However, we recorded robust responses from NE biosensors when they were positioned against mouse circumvallate taste buds and the taste buds were stimulated with KCl (50 mm) or a mixture of taste compounds (cycloheximide, 10 microm; saccharin, 2 mm; denatonium, 1 mm; SC45647, 100 microm). NE biosensor responses evoked by stimulating taste buds were reversibly blocked by prazosin, an alpha(1A) receptor antagonist. Together, these findings indicate that taste bud cells secrete NE when they are stimulated. We isolated individual taste bud cells to identify the origin of NE release. NE was secreted only from presynaptic (type III) taste cells and not receptor (type II) cells. Stimulus-evoked NE release depended on Ca(2+) in the bathing medium. Using dual biosensors (sensitive to 5-HT and NE), we found all presynaptic cells secrete 5-HT and 33% corelease NE with 5-HT.

Secretion of Pseudomonas aeruginosa type III cytotoxins is dependent on pseudomonas quinolone signal concentration.

PubMed

Singh, G; Wu, B; Baek, M S; Camargo, A; Nguyen, A; Slusher, N A; Srinivasan, R; Wiener-Kronish, J P; Lynch, S V

2010-10-01

Pseudomonas aeruginosa is an opportunistic pathogen that can, like other bacterial species, exist in antimicrobial resistant sessile biofilms and as free-swimming, planktonic cells. Specific virulence factors are typically associated with each lifestyle and several two component response regulators have been shown to reciprocally regulate transition between biofilm-associated chronic, and free-swimming acute infections. Quorum sensing (QS) signal molecules belonging to the las and rhl systems are known to regulate virulence gene expression by P. aeruginosa. However the impact of a recently described family of novel quorum sensing signals produced by the Pseudomonas Quinolone Signal (PQS) biosynthetic pathway, on the transition between these modes of infection is less clear. Using clonal isolates from a patient developing ventilator-associated pneumonia, we demonstrated that clinical observations were mirrored by an in vitro temporal shift in isolate phenotype from a non-secreting, to a Type III cytotoxin secreting (TTSS) phenotype and further, that this phenotypic change was PQS-dependent. While intracellular type III cytotoxin levels were unaffected by PQS concentration, cytotoxin secretion was dependent on this signal molecule. Elevated PQS concentrations were associated with inhibition of cytotoxin secretion coincident with expression of virulence factors such as elastase and pyoverdin. In contrast, low concentrations or the inability to biosynthesize PQS resulted in a reversal of this phenotype. These data suggest that expression of specific P. aeruginosa virulence factors appears to be reciprocally regulated and that an additional level of PQS-dependent post-translational control, specifically governing type III cytotoxin secretion, exists in this species. Copyright 2010 Elsevier Ltd. All rights reserved.

Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With Uterine Cancer

ClinicalTrials.gov

2015-01-16

Stage IA Uterine Sarcoma; Stage IB Uterine Sarcoma; Stage IC Uterine Sarcoma; Stage IIA Uterine Sarcoma; Stage IIB Uterine Sarcoma; Stage IIIA Uterine Sarcoma; Stage IIIB Uterine Sarcoma; Stage IIIC Uterine Sarcoma; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma; Uterine Carcinosarcoma

Paclitaxel and Intraperitoneal Carboplatin Followed by Radiation Therapy in Treating Patients With Stage IIIC-IV Uterine Cancer

ClinicalTrials.gov

2015-02-10

Endometrial Serous Adenocarcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC1 Uterine Corpus Cancer; Stage IIIC2 Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Synthesis of refractory materials

DOEpatents

Holt, Joseph B.

1984-01-01

Refractory metal nitrides are synthesized during a combustion process utilizing a solid source of nitrogen. For this purpose, a metal azide is employed. The azide is combusted with a transition metal of the IIIB, IVB group, or a rare earth metal, and ignited to produce the refractory material.

20 CFR 638.804 - Environmental health.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Environmental health. 638.804 Section 638.804... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.804 Environmental health. The Job Corps Director shall provide guidelines for proper environmental health conditions. ...

20 CFR 638.804 - Environmental health.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Environmental health. 638.804 Section 638.804... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.804 Environmental health. The Job Corps Director shall provide guidelines for proper environmental health conditions. ...

20 CFR 638.804 - Environmental health.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Environmental health. 638.804 Section 638.804... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.804 Environmental health. The Job Corps Director shall provide guidelines for proper environmental health conditions. ...

20 CFR 638.304 - Historical preservation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Historical preservation. 638.304 Section 638.304 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Funding, Site Selection, and Facilities Management...

Nivolumab in Treating Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer

ClinicalTrials.gov

2018-05-23

Nasopharyngeal Nonkeratinizing Carcinoma; Recurrent Nasopharynx Carcinoma; Stage III Nasopharyngeal Carcinoma AJCC v7; Stage IV Nasopharyngeal Carcinoma AJCC v7; Stage IVA Nasopharyngeal Carcinoma AJCC v7; Stage IVB Nasopharyngeal Carcinoma AJCC v7; Stage IVC Nasopharyngeal Carcinoma AJCC v7

Synthesis of refractory materials

DOEpatents

Holt, J.B.

Refractory metal nitrides are synthesized during a combustion process utilizing a solid source of nitrogen. For this purpose, a metal azide is employed. The azide is combusted with a transition metal of the IIIB, IVB group, or a rare earth metal, and ignited to produce the refractory material.

20 CFR 638.537 - Disclosure of information.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 638.537 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.537 Disclosure of information. (a) Requests for information. The Job Corps Director shall develop administrative procedures to...

20 CFR 638.539 - Complaints and disputes.

Code of Federal Regulations, 2010 CFR

2010-04-01

....539 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.539 Complaints and disputes. (a) Center and other deliverer grievance procedures. Each center operator or other Job Corps...

20 CFR 638.814 - Lobbying; political activities; unionization.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Lobbying; political activities; unionization. 638.814 Section 638.814 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions...

20 CFR 638.536 - Religious rights.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.536 Religious rights. The right... denomination. The center operator shall instruct students that students are not obligated by Job Corps to...

20 CFR 638.529 - Income taxes.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.529 Income taxes. The Act... 26, U.S. Code). The Job Corps Director may obtain from tax authorities information regarding taxation...

20 CFR 638.802 - Student records management.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 638.802 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.802 Student records management. The Job Corps Director shall develop guidelines for a system of maintaining records...

26 CFR 1.334-1 - Basis of property received in liquidations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... liquidation and if gain or loss is recognized on the receipt of such property, then the basis of the property...) is applicable. See § 1.460-4(k)(3)(iv)(B)(2) for rules relating to adjustments to the basis of...

26 CFR 1.334-1 - Basis of property received in liquidations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... liquidation and if gain or loss is recognized on the receipt of such property, then the basis of the property...) is applicable. See § 1.460-4(k)(3)(iv)(B)(2) for rules relating to adjustments to the basis of...

Spacecraft Chemical Propulsion Systems at NASA's Marshall Space Flight Center: Heritage and Capabilities

NASA Technical Reports Server (NTRS)

McRight, Patrick S.; Sheehy, Jeffrey A.; Blevins, John A.

2005-01-01

NASA Marshall Space Flight Center (MSFC) is well known for its contributions to large ascent propulsion systems such as the Saturn V and the Space Shuttle. This paper highlights a lesser known but equally rich side of MSFC - its heritage in spacecraft chemical propulsion systems and its current capabilities for in-space propulsion system development and chemical propulsion research. The historical narrative describes the efforts associated with developing upper-stage main propulsion systems such as the Saturn S-IVB as well as orbital maneuvering and reaction control systems such as the S-IVB auxiliary propulsion system, the Skylab thruster attitude control system, and many more recent activities such as Chandra, the Demonstration of Automated Rendezvous Technology, X-37, the X-38 de-orbit propulsion system, the Interim Control Module, the US Propulsion Module, and several technology development activities. Also discussed are MSFC chemical propulsion research capabilities, along with near- and long-term technology challenges to which MSFC research and system development competencies are relevant.

ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment

ClinicalTrials.gov

2018-03-02

Oral Cavity Neoplasm; Oropharyngeal Neoplasm; Stage I Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage I Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage II Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage II Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7

LEVEL A IN VITRO-IN-IVO CORRELATION DEVELOPMENT AND VALIDA- TION FOR TRAMADOL HYDROCHLORIDE FORMULATIONS.

PubMed

Cai, Yangping; Li, Youshan; Li, Shu; Gao, Tian; Zhang, Lu; Yang, Zhe; Fan, Zhengfu; Bai, Chujie

2016-09-01

The objective of this article is to develop and validate the level A in vitro-in vivo correlation (IVIVC) for three different formulations of tramadol hydrochloride. The formulations included were Tramazac® (Ml, conventional tablet) and TRD CONTIN® (M2, sustained release tablet), and a new controlled release tablet prepared on the basis of osmotic technology (formulation IVB). To develop level A IVIVC, in vivo data were deconvoluted into absorption data by using Wagner-Nelson equation. The absorption data (percent drug absorbed) was plotted against percent drug dissolved keeping the former along x-axis and the later along y-axis. The highest determination coefficient (R² = 0.9278) of the level A IVIVC was observed for formulation MI, and then for M2 (R² = 0.9046) and IVB (R² = 0.8796). Additionally, plasma drug levels were approximated from in vitio dissolution data using convolution approach to calculate the prediction error (%), which was found to be < 10%.

Expression, Extracellular Secretion, and Immunogenicity of the Plasmodium falciparum Sporozoite Surface Protein 2 in Salmonella Vaccine Strains

PubMed Central

Gómez-Duarte, Oscar G.; Pasetti, Marcela F.; Santiago, Araceli; Sztein, Marcelo B.; Hoffman, Stephen L.; Levine, Myron M.

2001-01-01

Deleting transmembrane α-helix motifs from Plasmodium falciparum sporozoite surface protein (SSP-2) allowed its secretion from Salmonella enterica serovar Typhimurium SL3261 and S. enterica serovar Typhi CVD 908-htrA by the Hly type I secretion system. In mice immunized intranasally, serovar Typhimurium constructs secreting SSP-2 stimulated greater gamma interferon splenocyte responses than did nonsecreting constructs (P = 0.04). PMID:11160021

The type III secretion system needle tip complex mediates host cell sensing and translocon insertion.

PubMed

Veenendaal, Andreas K J; Hodgkinson, Julie L; Schwarzer, Lynn; Stabat, David; Zenk, Sebastian F; Blocker, Ariel J

2007-03-01

Type III secretion systems (T3SSs) are essential virulence determinants of many Gram-negative bacterial pathogens. The Shigella T3SS consists of a cytoplasmic bulb, a transmembrane region and a hollow 'needle' protruding from the bacterial surface. Physical contact with host cells initiates secretion and leads to assembly of a pore, formed by IpaB and IpaC, in the host cell membrane, through which proteins that facilitate host cell invasion are translocated. As the needle is implicated in host cell sensing and secretion regulation, its tip should contain components that initiate host cell contact. Through biochemical and immunological studies of wild-type and mutant Shigella T3SS needles, we reveal tip complexes of differing compositions and functional states, which appear to represent the molecular events surrounding host cell sensing and pore formation. Our studies indicate that the interaction between IpaB and IpaD at needle tips is key to host cell sensing, orchestration of IpaC secretion and its subsequent assembly at needle tips. This allows insertion into the host cell membrane of a translocation pore that is continuous with the needle.

The Ruler Protein EscP of the Enteropathogenic Escherichia coli Type III Secretion System Is Involved in Calcium Sensing and Secretion Hierarchy Regulation by Interacting with the Gatekeeper Protein SepL

PubMed Central

Shaulov, Lihi; Gershberg, Jenia; Deng, Wanyin; Finlay, B. Brett

2017-01-01

ABSTRACT The type III secretion system (T3SS) is a multiprotein complex that plays a central role in the virulence of many Gram-negative bacterial pathogens. To ensure that effector proteins are efficiently translocated into the host cell, bacteria must be able to sense their contact with the host cell. In this study, we found that EscP, which was previously shown to function as the ruler protein of the enteropathogenic Escherichia coli T3SS, is also involved in the switch from the secretion of translocator proteins to the secretion of effector proteins. In addition, we demonstrated that EscP can interact with the gatekeeper protein SepL and that the EscP-SepL complex dissociates upon a calcium concentration drop. We suggest a model in which bacterial contact with the host cell is accompanied by a drop in the calcium concentration that causes SepL-EscP complex dissociation and triggers the secretion of effector proteins. PMID:28049143

Targeting bacterial secretion systems: benefits of disarmament in the microcosm.

PubMed

Baron, Christian; Coombes, Brian

2007-03-01

Secretion systems are used by many bacterial pathogens for the delivery of virulence factors to the extracellular space or directly into host cells. They are attractive targets for the development of novel anti-virulence drugs as their inactivation would lead to pathogen attenuation or avirulence, followed by clearance of the bacteria by the immune system. This review will present the state of knowledge on the assembly and function of type II, type III and type IV secretion systems in Gram-negative bacteria focusing on insights provided by structural analyses of several key components. The suitability of transcription factors regulating the expression of secretion system components and of ATPases, lytic transglycosylases and protein assembly factors as drug targets will be discussed. Recent progress using innovative in vivo as well as in vitro screening strategies led to a first set of secretion system inhibitors with potential for further development as anti-infectives. The discovery of such inhibitors offers exciting and innovative opportunities to further develop these anti-virulence drugs into monotherapy or in combination with classical antibiotics. Bacterial growth per se would not be inhibited by such drugs so that the selection for mutations causing resistance could be reduced. Secretion system inhibitors may therefore avoid many of the problems associated with classical antibiotics and may constitute a valuable addition to our arsenal for the treatment of bacterial infections.

Analysis of the ZAR1 immune complex reveals determinants for immunity and molecular interactions

USDA-ARS?s Scientific Manuscript database

Plants depend on innate immunity to prevent disease. Plant pathogenic bacteria, like Pseudomonas syringae and Xanthomonas campestris, use the type III secretion system as a molecular syringe to inject type III secreted effector (T3SE) proteins in plants. The primary function of most T3SEs is to supp...

Functional and computational analysis of amino acid patterns predictive of type III secretion system substrates in Pseudomonas syringae

USDA-ARS?s Scientific Manuscript database

Bacterial type III secretion systems (T3SSs) deliver proteins called effectors into eukaryotic cells. Although N-terminal amino acid sequences are required for translocation, the mechanism of substrate recognition by the T3SS is unknown. Almost all actively deployed T3SS substrates in the plant path...

Die another day: molecular mechanisms of effector-triggered immunity elicited by type III secreted effector proteins

USDA-ARS?s Scientific Manuscript database

Bacterial pathogens inject type III secreted effector (T3SE) proteins into their hosts where they display dual roles depending on the host genotype. T3SEs promote bacterial virulence in susceptible hosts, and elicit immunity in resistant hosts. T3SEs are typically recognized when they modify a host ...

Draft Genome Sequence of Chryseobacterium sp. JV274 Isolated from Maize Rhizosphere

PubMed Central

Vacheron, Jordan; Dubost, Audrey; Chapulliot, David; Prigent-Combaret, Claire

2017-01-01

ABSTRACT We report the draft genome sequence of Chryseobacterium sp. JV274. This strain was isolated from the rhizosphere of maize during a greenhouse experiment. JV274 harbors genes involved in flexirubin production (darA and darB genes), bacterial competition (type VI secretion system), and gliding (bacterial motility; type IX secretion system). PMID:28408666

Visualization and characterization of individual type III protein secretion machines in live bacteria

PubMed Central

Lara-Tejero, María; Bewersdorf, Jörg; Galán, Jorge E.

2017-01-01

Type III protein secretion machines have evolved to deliver bacterially encoded effector proteins into eukaryotic cells. Although electron microscopy has provided a detailed view of these machines in isolation or fixed samples, little is known about their organization in live bacteria. Here we report the visualization and characterization of the Salmonella type III secretion machine in live bacteria by 2D and 3D single-molecule switching superresolution microscopy. This approach provided access to transient components of this machine, which previously could not be analyzed. We determined the subcellular distribution of individual machines, the stoichiometry of the different components of this machine in situ, and the spatial distribution of the substrates of this machine before secretion. Furthermore, by visualizing this machine in Salmonella mutants we obtained major insights into the machine’s assembly. This study bridges a major resolution gap in the visualization of this nanomachine and may serve as a paradigm for the examination of other bacterially encoded molecular machines. PMID:28533372

Proteins Exported via the PrsD-PrsE Type I Secretion System and the Acidic Exopolysaccharide Are Involved in Biofilm Formation by Rhizobium leguminosarum

PubMed Central

Russo, Daniela M.; Williams, Alan; Edwards, Anne; Posadas, Diana M.; Finnie, Christine; Dankert, Marcelo; Downie, J. Allan; Zorreguieta, Angeles

2006-01-01

The type I protein secretion system of Rhizobium leguminosarum bv. viciae encoded by the prsD and prsE genes is responsible for secretion of the exopolysaccharide (EPS)-glycanases PlyA and PlyB. The formation of a ring of biofilm on the surface of the glass in shaken cultures by both the prsD and prsE secretion mutants was greatly affected. Confocal laser scanning microscopy analysis of green-fluorescent-protein-labeled bacteria showed that during growth in minimal medium, R. leguminosarum wild type developed microcolonies, which progress to a characteristic three-dimensional biofilm structure. However, the prsD and prsE secretion mutants were able to form only an immature biofilm structure. A mutant disrupted in the EPS-glycanase plyB gene showed altered timing of biofilm formation, and its structure was atypical. A mutation in an essential gene for EPS synthesis (pssA) or deletion of several other pss genes involved in EPS synthesis completely abolished the ability of R. leguminosarum to develop a biofilm. Extracellular complementation studies of mixed bacterial cultures confirmed the role of the EPS and the modulation of the biofilm structure by the PrsD-PrsE secreted proteins. Protein analysis identified several additional proteins secreted by the PrsD-PrsE secretion system, and N-terminal sequencing revealed peptides homologous to the N termini of proteins from the Rap family (Rhizobium adhering proteins), which could have roles in cellular adhesion in R. leguminosarum. We propose a model for R. leguminosarum in which synthesis of the EPS leads the formation of a biofilm and several PrsD-PrsE secreted proteins are involved in different aspects of biofilm maturation, such as modulation of the EPS length or mediating attachment between bacteria. PMID:16740954

Abridged republication of FIGO's staging classification for cancer of the ovary, fallopian tube, and peritoneum.

PubMed

Prat, Jaime

2015-10-01

Ovarian, fallopian tube, and peritoneal cancers have a similar clinical presentation and are treated similarly, and current evidence supports staging all 3 cancers in a single system. The primary site (i.e. ovary, fallopian tube, or peritoneum) should be designated where possible. The histologic type should be recorded. Intraoperative rupture ("surgical spill") is IC1; capsule ruptured before surgery or tumor on ovarian or fallopian tube surface is IC2; and positive peritoneal cytology with or without rupture is IC3. The new staging includes a revision of stage III patients; assignment to stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination. Extension of tumor from omentum to spleen or liver (stage IIIC) should be differentiated from isolated parenchymal metastases (stage IVB). © 2015 American Cancer Society.

C-type natriuretic peptide is synthesized and secreted from leukemia cell lines, peripheral blood cells, and peritoneal macrophages.

PubMed

Kubo, A; Isumi, Y; Ishizaka, Y; Tomoda, Y; Kangawa, K; Dohi, K; Matsuo, H; Minamino, N

2001-05-01

C-type natriuretic peptide (CNP) is the third member of the natriuretic peptide family. Cultured endothelial cells secrete CNP, and its secretion rate from the endothelial cells is augmented by lipopolysaccharide, interleukin-1beta, and tumor necrosis factor-alpha, which participate in the pathophysiology of inflammation. In this study, we investigated the regulation of CNP secretion from monocytes and macrophages to estimate its contribution to the progression of inflammation. CNP secretion rates from two human leukemia cell lines (THP-1 and HL-60), human peripheral blood lymphocytes, granulocytes, monocytes, monocyte-derived macrophages, and mouse peritoneal macrophages were measured under conditions with or without stimulation. Immunoreactive CNP levels in the culture media of these cells were measured by a specific radioimmunoassay. The secretion rates of CNP from THP-1 and HL-60 cells were augmented according to the degree of their differentiation into macrophage-like cells under the stimulation with phorbol ester. Peripheral blood monocytes also increased the CNP secretion rate after their differentiation into macrophages. Retinoic acid elicited synergistic effects on the CNP secretion rate from HL-60 cells when administered with lipopolysaccharide, interferon-gamma, interleukin-1beta, tumor necrosis factor-alpha, or phorbol ester. In contrast, the phorbol ester-stimulated CNP secretion rate from THP-1 cells was suppressed with dexamethasone, which inhibits monocyte differentiation into macrophage. The secretion rate of CNP from monocytes was shown to be regulated based on the degree of their differentiation. This study provides evidence that the monocyte/macrophage system is one of the sources of CNP, especially under inflammatory conditions.

Single-Cell Detection of Secreted Aβ and sAPPα from Human IPSC-Derived Neurons and Astrocytes.

PubMed

Liao, Mei-Chen; Muratore, Christina R; Gierahn, Todd M; Sullivan, Sarah E; Srikanth, Priya; De Jager, Philip L; Love, J Christopher; Young-Pearse, Tracy L

2016-02-03

Secreted factors play a central role in normal and pathological processes in every tissue in the body. The brain is composed of a highly complex milieu of different cell types and few methods exist that can identify which individual cells in a complex mixture are secreting specific analytes. By identifying which cells are responsible, we can better understand neural physiology and pathophysiology, more readily identify the underlying pathways responsible for analyte production, and ultimately use this information to guide the development of novel therapeutic strategies that target the cell types of relevance. We present here a method for detecting analytes secreted from single human induced pluripotent stem cell (iPSC)-derived neural cells and have applied the method to measure amyloid β (Aβ) and soluble amyloid precursor protein-alpha (sAPPα), analytes central to Alzheimer's disease pathogenesis. Through these studies, we have uncovered the dynamic range of secretion profiles of these analytes from single iPSC-derived neuronal and glial cells and have molecularly characterized subpopulations of these cells through immunostaining and gene expression analyses. In examining Aβ and sAPPα secretion from single cells, we were able to identify previously unappreciated complexities in the biology of APP cleavage that could not otherwise have been found by studying averaged responses over pools of cells. This technique can be readily adapted to the detection of other analytes secreted by neural cells, which would have the potential to open new perspectives into human CNS development and dysfunction. We have established a technology that, for the first time, detects secreted analytes from single human neurons and astrocytes. We examine secretion of the Alzheimer's disease-relevant factors amyloid β (Aβ) and soluble amyloid precursor protein-alpha (sAPPα) and present novel findings that could not have been observed without a single-cell analytical platform. First, we identify a previously unappreciated subpopulation that secretes high levels of Aβ in the absence of detectable sAPPα. Further, we show that multiple cell types secrete high levels of Aβ and sAPPα, but cells expressing GABAergic neuronal markers are overrepresented. Finally, we show that astrocytes are competent to secrete high levels of Aβ and therefore may be a significant contributor to Aβ accumulation in the brain. Copyright © 2016 the authors 0270-6474/16/361730-17$15.00/0.

PCV2 on the spot-A new method for the detection of single porcine circovirus type 2 secreting cells.

PubMed

Fossum, Caroline; Hjertner, Bernt; Lövgren, Tanja; Fuxler, Lisbeth; Charerntantanakul, Wasin; Wallgren, Per

2014-02-01

A porcine circovirus type 2 SPOT (PCV2-SPOT) assay was established to enumerate virus-secreting lymphocytes obtained from naturally infected pigs. The assay is based on the same principle as general ELISPOT assays but instead of detecting cytokine or immunoglobulin secretion, PCV2 particles are immobilized and detected as filter spots. The method was used to evaluate the influence of various cell activators on the PCV2 secretion in vitro and was also applied to study the PCV2 secretion by lymphocytes obtained from pigs in healthy herds and in a herd afflicted by postweaning multisystemic wasting disease (PMWS). Peripheral blood mononuclear cells (PBMCs) obtained from a pig with severe PMWS produced PCV2-SPOTs spontaneously whereas PBMCs obtained from pigs infected subclinically only generated PCV2-SPOTs upon in vitro stimulation. The PCV2 secretion potential was related to the PCV2 DNA content in the PBMCs as determined by two PCV2 real-time PCR assays, developed to differentiate between Swedish PCV2 genogroups 1 (PCV2a) and 3 (PCV2b). Besides the current application these qPCRs could simplify future epidemiological studies and allow genogroup detection/quantitation in dual infection experiments and similar studies. The developed PCV2-SPOT assay offers a semi-quantitative approach to evaluate the potential of PCV2-infected porcine cells to release PCV2 viral particles as well as a system to evaluate the ability of different cell types or compounds to affect PCV2 replication and secretion. Copyright © 2013 Elsevier B.V. All rights reserved.

Twin-arginine signal peptide of Bacillus subtilis YwbN can direct Tat-dependent secretion of methyl parathion hydrolase.

PubMed

Liu, Ruihua; Zuo, Zhenqiang; Xu, Yingming; Song, Cunjiang; Jiang, Hong; Qiao, Chuanling; Xu, Ping; Zhou, Qixing; Yang, Chao

2014-04-02

The twin-arginine translocation (Tat) pathway exports folded proteins across the cytoplasmic membranes of bacteria and archaea. Two parallel Tat pathways (TatAdCd and TatAyCy systems) with distinct substrate specificities have previously been discovered in Bacillus subtilis. In this study, to secrete methyl parathion hydrolase (MPH) into the growth medium, the twin-arginine signal peptide of B. subtilis YwbN was used to target MPH to the Tat pathway of B. subtilis. Western blot analysis and MPH assays demonstrated that active MPH was secreted into the culture supernatant of wild-type cells. No MPH secretion occurred in a total-tat2 mutant, indicating that the observed export in wild-type cells was mediated exclusively by the Tat pathway. Export was fully blocked in a tatAyCy mutant. In contrast, the tatAdCd mutant was still capable of secreting MPH. These results indicated that the MPH secretion directed by the YwbN signal peptide was specifically mediated by the TatAyCy system. The N-terminal sequence of secreted MPH was determined as AAPQVR, demonstrating that the YwbN signal peptide had been processed correctly. This is the first report of functional secretion of a heterologous protein via the B. subtilis TatAyCy system. This study highlights the potential of the TatAyCy system to be used for secretion of other heterologous proteins in B. subtilis.

20 CFR 638.503 - Vocational training.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Vocational training. 638.503 Section 638.503 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.503 Vocational training. (a) Each...

Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

ClinicalTrials.gov

2017-06-30

Advanced Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Hepatocellular Carcinoma; Stage III Childhood Hepatocellular Carcinoma; Stage IIIA Hepatocellular Carcinoma; Stage IIIB Hepatocellular Carcinoma; Stage IIIC Hepatocellular Carcinoma; Stage IV Childhood Hepatocellular Carcinoma; Stage IVA Hepatocellular Carcinoma; Stage IVB Hepatocellular Carcinoma

Theoretical Studies of Group IVA and Group IVB Chemistry

DTIC Science & Technology

2012-01-13

novel ionic liquids . We have performed very high level CCSD(T) calculations on one such species, Al13- to predict its ionization potential in nearly...Precursors. Polyhedral oligomeric silsesquioxanes (POSS) are three- dimensional Si-O cage compounds that have many uses, because of their resistance

20 CFR 638.800 - Program management.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Program management. 638.800 Section 638.800... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.800 Program management. (a) The Job Corps Director shall establish and use internal program management procedures sufficient...

20 CFR 638.800 - Program management.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Program management. 638.800 Section 638.800... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.800 Program management. (a) The Job Corps Director shall establish and use internal program management procedures sufficient...

20 CFR 638.305 - Capital improvements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Capital improvements. 638.305 Section 638.305 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Funding, Site Selection, and Facilities Management § 638...

20 CFR 638.409 - Placement and job development.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Placement and job development. 638.409 Section 638.409 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Enrollment, Transfers, Terminations, and...

20 CFR 638.409 - Placement and job development.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Placement and job development. 638.409 Section 638.409 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Enrollment, Transfers, Terminations, and...

20 CFR 638.409 - Placement and job development.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Placement and job development. 638.409 Section 638.409 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Enrollment, Transfers, Terminations, and...

20 CFR 638.500 - Orientation program.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Orientation program. 638.500 Section 638.500 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.500 Orientation program. The...

20 CFR 638.800 - Program management.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Program management. 638.800 Section 638.800... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.800 Program management. (a) The Job Corps Director shall establish and use internal program management procedures sufficient...

Nivolumab and Ipilimumab in Treating Patients With Metastatic/Recurrent ACC of All Sites and Non-ACC Salivary Gland Cancer

ClinicalTrials.gov

2018-04-12

Major Salivary Gland Carcinoma; Minor Salivary Gland Carcinoma; Recurrent Salivary Gland Carcinoma; Stage IV Major Salivary Gland Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVC Major Salivary Gland Carcinoma

20 CFR 638.525 - Clothing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Clothing. 638.525 Section 638.525 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.525 Clothing. The Job Corps Director shall...

20 CFR 638.807 - Imprest and petty cash funds.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 638.807 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.807 Imprest... centers shall establish auditable petty cash funds. The Job Corps Director shall develop procedures to...

20 CFR 638.806 - Property management and procurement.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Section 638.806 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Administrative Provisions § 638.806 Property management and procurement. The Job Corps Director shall develop procedures to establish and maintain a...

20 CFR 638.534 - Legal services to students.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 638.534 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.534 Legal services to students. (a) The Job Corps Director shall develop procedures to afford students effective and competent...

20 CFR 638.503 - Vocational training.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.503 Vocational training. (a) Each... training programs offered at individual centers will be subject to the approval of the Job Corps Director...

20 CFR 638.538 - Disciplinary procedures and appeals.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Section 638.538 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.538 Disciplinary... behavior, in accordance with procedures developed by the Job Corps Director. Such rules shall be...

20 CFR 638.521 - Student welfare association.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 638.521 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.521 Student welfare... center staff advisor. This plan shall be developed in accordance with procedures issued by the Job Corps...

20 CFR 638.543 - Community relations program.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Community relations program. 638.543 Section 638.543 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.543 Community...

20 CFR 638.533 - Other student absences.

Code of Federal Regulations, 2010 CFR

2010-04-01

....533 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.533 Other student absences. The Job Corps Director shall develop procedures for authorized student absences and to account for all...

20 CFR 638.301 - Funding procedures.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Funding procedures. 638.301 Section 638.301... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Funding, Site Selection, and Facilities Management § 638.301 Funding procedures. (a) Contracting officers shall request proposals for the operation of all...

20 CFR 638.301 - Funding procedures.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Funding procedures. 638.301 Section 638.301... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Funding, Site Selection, and Facilities Management § 638.301 Funding procedures. (a) Contracting officers shall request proposals for the operation of all...

26 CFR 1.362-1 - Basis to corporations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... basis shall be the same as it would be in the hands of the transferor, increased in the amount of gain recognized to the transferor on such transfer. (See also § 1.362-2.) See § 1.460-4(k)(3)(iv)(B)(2) for rules...

26 CFR 1.362-1 - Basis to corporations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... basis shall be the same as it would be in the hands of the transferor, increased in the amount of gain recognized to the transferor on such transfer. (See also § 1.362-2.) See § 1.460-4(k)(3)(iv)(B)(2) for rules...

Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With High-Risk Endometrial Cancer

ClinicalTrials.gov

2016-01-11

Endometrial Adenocarcinoma; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Two Missions, One Secret Service: The Value of the Investigative Mission

DTIC Science & Technology

2011-09-01

a result, support and attention for the investigative mission has waned. This lack of attention to investigations is dangerous for the Secret Service...thesis argues that the types of investigations performed by the Secret Service are not as important as the experiential learning, respite from the...in these three important ways, the Secret Service requires a robust, well-funded and substantial investigative mission to continue to properly provide protection to this nation’s leaders.

Structure of a PE-PPE-EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion

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

Ekiert, Damian C.; Cox, Jeffery S.

Nearly 10% of the coding capacity of the Mycobacterium tuberculosis genome is devoted to two highly expanded and enigmatic protein families called PE and PPE, some of which are important virulence/immunogenicity factors and are secreted during infection via a unique alternative secretory system termed "type VII." How PE-PPE proteins function during infection and how they are translocated to the bacterial surface through the five distinct type VII secretion systems [ESAT-6 secretion system (ESX)] of M. tuberculosis is poorly understood. Here in this paper, we report the crystal structure of a PE-PPE heterodimer bound to ESX secretion-associated protein G (EspG), whichmore » adopts a novel fold. This PE-PPE-EspG complex, along with structures of two additional EspGs, suggests that EspG acts as an adaptor that recognizes specific PE-PPE protein complexes via extensive interactions with PPE domains, and delivers them to ESX machinery for secretion. Surprisingly, secretion of most PE-PPE proteins in M. tuberculosis is likely mediated by EspG from the ESX-5 system, underscoring the importance of ESX-5 in mycobacterial pathogenesis. Furthermore, our results indicate that PE-PPE domains function as cis-acting targeting sequences that are read out by EspGs, revealing the molecular specificity for secretion through distinct ESX pathways.« less

Structure of a PE-PPE-EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion

DOE PAGES

Ekiert, Damian C.; Cox, Jeffery S.

2014-10-01

Nearly 10% of the coding capacity of the Mycobacterium tuberculosis genome is devoted to two highly expanded and enigmatic protein families called PE and PPE, some of which are important virulence/immunogenicity factors and are secreted during infection via a unique alternative secretory system termed "type VII." How PE-PPE proteins function during infection and how they are translocated to the bacterial surface through the five distinct type VII secretion systems [ESAT-6 secretion system (ESX)] of M. tuberculosis is poorly understood. Here in this paper, we report the crystal structure of a PE-PPE heterodimer bound to ESX secretion-associated protein G (EspG), whichmore » adopts a novel fold. This PE-PPE-EspG complex, along with structures of two additional EspGs, suggests that EspG acts as an adaptor that recognizes specific PE-PPE protein complexes via extensive interactions with PPE domains, and delivers them to ESX machinery for secretion. Surprisingly, secretion of most PE-PPE proteins in M. tuberculosis is likely mediated by EspG from the ESX-5 system, underscoring the importance of ESX-5 in mycobacterial pathogenesis. Furthermore, our results indicate that PE-PPE domains function as cis-acting targeting sequences that are read out by EspGs, revealing the molecular specificity for secretion through distinct ESX pathways.« less

Xanthine oxidoreductase mediates membrane docking of milk-fat droplets but is not essential for apocrine lipid secretion.

PubMed

Monks, Jenifer; Dzieciatkowska, Monika; Bales, Elise S; Orlicky, David J; Wright, Richard M; McManaman, James L

2016-10-15

Xanthine oxidoreductase (XOR) modulates milk lipid secretion and lactation initiation. XOR is required for butyrophilin1a1 clustering in the membrane during milk lipid secretion. XOR mediates apical membrane reorganization during milk lipid secretion. Loss of XOR delays milk fat globule secretion. XOR loss alters the proteome of milk fat globules. Apocrine secretion is utilized by epithelial cells of exocrine glands. These cells bud off membrane-bound particles into the lumen of the gland, losing a portion of the cytoplasm in the secretion product. The lactating mammary gland secretes milk lipid by this mechanism, and xanthine oxidoreductase (XOR) has long been thought to be functionally important. We generated mammary-specific XOR knockout (MGKO) mice, expecting lactation to fail. Histology of the knockout glands showed very large lipid droplets enclosed in the mammary alveolar cells, but milk analysis showed that these large globules were secreted. Butyrophilin, a membrane protein known to bind to XOR, was clustered at the point of contact of the cytoplasmic lipid droplet with the apical plasma membrane, in the wild-type gland but not in the knockout, suggesting that XOR mediates 'docking' to this membrane. Secreted milk fat globules were isolated from mouse milk of wild-type and XOR MGKO dams, and subjected to LC-MS/MS for analysis of protein component. Proteomic results showed that loss of XOR leads to an increase in cytoplasmic, cytoskeletal, Golgi apparatus and lipid metabolism proteins associated with the secreted milk fat globule. Association of XOR with the lipid droplet results in membrane docking and more efficient retention of cytoplasmic components by the secretory cell. Loss of XOR then results in a reversion to a more rudimentary, less efficient, apocrine secretion mechanism, but does not prevent milk fat globule secretion. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

The unconventional secretion of IL-1β: Handling a dangerous weapon to optimize inflammatory responses.

PubMed

Sitia, Roberto; Rubartelli, Anna

2018-04-04

Interleukin 1β (IL-1β) is a major mediator of inflammation, with a causative role in many diseases. Unlike most other cytokines, however, it lacks a secretory signal sequence, raising intriguing mechanistic, functional and evolutionary questions. Despite decades of strenuous efforts in many laboratories, how IL-1β is secreted is still a matter of intense debate. Here, we summarize the different mechanisms and pathways that have been proposed for IL-1β secretion. At least two of them, namely the endolysosomal vesicle-based and gasdermin D-dependent pathways (types III and I in the recent Rabouille's classification of unconventional protein secretion), can be triggered in monocytes, the main source of IL-1β in humans, according to the type and strength of the pro-inflammatory stimuli. As during the escalation of human conflicts, monocytes deploy secretory mechanisms of increasing efficiency and dangerousness, shifting from the specific and controlled type III pathway to the much faster release of type I. Thus, the different mechanisms are activated depending on the severity of the conditions, from the self-limiting type III pathways in response of low pathogen load or small trauma, to the uncontrolled responses that underlie autoinflammatory disorders and sepsis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Morphologic classification of the right auricule on 256-slice computed tomography.

PubMed

Li, Cai-Ying; Gao, Bu-Lang; Pan, Tong; Xiang, Cheng; Liu, Xiao-Wei; Yang, Hai-Qing; Yi, Lan-Ying; Liao, Qi-Bin

2017-06-01

To investigate the shape of right auricule on 256-slice computed tomography (CT). Five hundred people (250 men, age range 16-84 years) who had cardiac multidetector CT angiography were recruited in this study. All patients had normal sinus rhythm with normal blood pressure (<140/90 mmHg for systolic/diastolic pressure). The morphology of the right auricule was studied and compared after reconstruction of the raw images. All patients successfully had cardiac CT angiography (100%), and the right auricule morphology was divided into five types and nine subtypes, including Type I of triangular shape (Ia and Ib), Type II of M shape (IIa and IIb), Type III of L shape (IIIa and IIIb), Type IV of reverse L shape (IVa and IVb), and Type V of balanced shape. The most common type of right auricule is Type IV (28.4%) followed by Type II (24.0%), whereas the least common is Type V (11.0%). Type Ia was present significantly (P < 0.0001) more frequently in females than in males, whereas Type IIa significantly (P = 0.042) more frequently in males than females. No other significant (P > 0.05) sex difference existed in the constitution ratio of the types. The normal angle was greater in Type Ib than in Ia. The greater the normal angle in Type I, the greater the deviation of the right auricule tip towards the left. A good understanding of the right auricule anatomical morphology can better guide atrial pacing, radiofrequency ablation and other surgical procedures while preventing possible intra-procedural complications.

Trade Secret Law and Information Systems: Can Your Students Keep a Secret?

ERIC Educational Resources Information Center

Willey, Lorrie; Ford, Janet C.; White, Barbara Jo; Clapper, Danial L.

2011-01-01

The impact of intellectual property (IP) law on information systems (IS) professionals in business cannot be overstated. The IS 2010 model curriculum guidelines for undergraduate IS programs stress the importance of information security and knowledge about IP. While copyright and patents are the most well-known types of IP, another, trade secrets,…

Pathoadaptive Conditional Regulation of the Type VI Secretion System in Vibrio cholerae O1 Strains

PubMed Central

Ishikawa, Takahiko; Sabharwal, Dharmesh; Bröms, Jeanette; Milton, Debra L.; Sjöstedt, Anders; Uhlin, Bernt Eric

2012-01-01

The most recently discovered secretion pathway in Gram-negative bacteria, the type VI secretion system (T6SS), is present in many species and is considered important for the survival of non-O1 non-O139 Vibrio cholerae in aquatic environments. Until now, it was not known whether there is a functionally active T6SS in wild-type V. cholerae O1 strains, the cause of cholera disease in humans. Here, we demonstrate the presence of a functionally active T6SS in wild-type V. cholerae O1 strains, as evidenced by the secretion of the T6SS substrate Hcp, which required several gene products encoded within the putative vas gene cluster. Our analyses showed that the T6SS of wild-type V. cholerae O1 strain A1552 was functionally activated when the bacteria were grown under high-osmolarity conditions. The T6SS was also active when the bacteria were grown under low temperature (23°C), suggesting that the system may be important for the survival of the bacterium in the environment. A test of the interbacterial virulence of V. cholerae strain A1552 against an Escherichia coli K-12 strain showed that it was strongly enhanced under high osmolarity and that it depended on the hcp genes. Interestingly, we found that the newly recognized osmoregulatory protein OscR plays a role in the regulation of T6SS gene expression and secretion of Hcp from V. cholerae O1 strains. PMID:22083711

IcmS-dependent translocation of SdeA into macrophages by the Legionella pneumophila type IV secretion system.

PubMed

Bardill, J Patrick; Miller, Jennifer L; Vogel, Joseph P

2005-04-01

Legionella pneumophila replicates inside alveolar macrophages and causes an acute, potentially fatal pneumonia called Legionnaires' disease. The ability of this bacterium to grow inside of macrophages is dependent on the presence of a functional dot/icm type IV secretion system (T4SS). Proteins secreted by the Dot/Icm T4SS are presumed to alter the host endocytic pathway, allowing L. pneumophila to establish a replicative niche within the host cell. Here we show that a member of the SidE family of proteins interacts with IcmS and is required for full virulence in the protozoan host Acanthamoeba castellanii. Using immunofluorescence microscopy and adenylate cyclase fusions, we show that SdeA is secreted into host cells by L. pneumophila in an IcmS-dependent manner. The SidE-like proteins are secreted very early during macrophage infection, suggesting that they are important in the initial formation of the replicative phagosome. Secreted SidE family members show a similar localization to other Dot/Icm substrates, specifically, to the poles of the replicative phagosome. This common localization of secreted substrates of the Dot/Icm system may indicate the formation of a multiprotein complex on the cytoplasmic face of the replicative phagosome.

Deletion of flbA results in increased secretome complexity and reduced secretion heterogeneity in colonies of Aspergillus niger.

PubMed

Krijgsheld, Pauline; Nitsche, Benjamin M; Post, Harm; Levin, Ana M; Müller, Wally H; Heck, Albert J R; Ram, Arthur F J; Altelaar, A F Maarten; Wösten, Han A B

2013-04-05

Aspergillus niger is a cell factory for the production of enzymes. This fungus secretes proteins in the central part and at the periphery of the colony. The sporulating zone of the colony overlapped with the nonsecreting subperipheral zone, indicating that sporulation inhibits protein secretion. Indeed, strain ΔflbA that is affected early in the sporulation program secreted proteins throughout the colony. In contrast, the ΔbrlA strain that initiates but not completes sporulation did not show altered spatial secretion. The secretome of 5 concentric zones of xylose-grown ΔflbA colonies was assessed by quantitative proteomics. In total 138 proteins with a signal sequence for secretion were identified in the medium of ΔflbA colonies. Of these, 18 proteins had never been reported to be part of the secretome of A. niger, while 101 proteins had previously not been identified in the culture medium of xylose-grown wild type colonies. Taken together, inactivation of flbA results in spatial changes in secretion and in a more complex secretome. The latter may be explained by the fact that strain ΔflbA has a thinner cell wall compared to the wild type, enabling efficient release of proteins. These results are of interest to improve A. niger as a cell factory.

Pseudomonas syringae pv. Tomato DC3000 Type III secretion effector polymutants reveal an interplay between hopAD1 and AvrPtoB

USDA-ARS?s Scientific Manuscript database

The model pathogen Pseudomonas syringae pv. tomato DC3000 suppresses the two-tiered innate immune system of plants by injecting a complex repertoire of effector proteins into host cells via the type III secretion system. The model effector AvrPtoB has multiple domains and plant protein interactors i...

Further Characterization of a Type III Secretion System (T3SS) and of a New Effector Protein from a Clinical Isolate of Aeromonas Hydrophila - Part I

EPA Science Inventory

A type III secretion system (T3SS)-associated cytotoxin, AexT, with ADP-ribosyltransferase activity and homology to Pseudomonas aeruginosa bifuncational toxins ExoT/S, was recently identified from a fish pathogen Aeromonas salmonicida. In this study, we reported the molecular cha...

The Opportunistic Pathogen Serratia marcescens Utilizes Type VI Secretion To Target Bacterial Competitors ▿†

PubMed Central

Murdoch, Sarah L.; Trunk, Katharina; English, Grant; Fritsch, Maximilian J.; Pourkarimi, Ehsan; Coulthurst, Sarah J.

2011-01-01

The type VI secretion system (T6SS) is the most recently described and least understood of the protein secretion systems of Gram-negative bacteria. It is widely distributed and has been implicated in the virulence of various pathogens, but its mechanism and exact mode of action remain to be defined. Additionally there have been several very recent reports that some T6SSs can target bacteria rather than eukaryotic cells. Serratia marcescens is an opportunistic enteric pathogen, a class of bacteria responsible for a significant proportion of hospital-acquired infections. We describe the identification of a functional T6SS in S. marcescens strain Db10, the first report of type VI secretion by an opportunist enteric bacterium. The T6SS of S. marcescens Db10 is active, with secretion of Hcp to the culture medium readily detected, and is expressed constitutively under normal growth conditions from a large transcriptional unit. Expression of the T6SS genes did not appear to be dependent on the integrity of the T6SS. The S. marcescens Db10 T6SS is not required for virulence in three nonmammalian virulence models. It does, however, exhibit dramatic antibacterial killing activity against several other bacterial species and is required for S. marcescens to persist in a mixed culture with another opportunist pathogen, Enterobacter cloacae. Importantly, this antibacterial killing activity is highly strain specific, with the S. marcescens Db10 T6SS being highly effective against another strain of S. marcescens with a very similar and active T6SS. We conclude that type VI secretion plays a crucial role in the competitiveness, and thus indirectly the virulence, of S. marcescens and other opportunistic bacterial pathogens. PMID:21890705

Normal and abnormal secretion by haemopoietic cells

PubMed Central

STINCHCOMBE, JANE C; GRIFFITHS, GILLIAN M

2001-01-01

The secretory lysosomes found in haemopoietic cells provide a very efficient mechanism for delivering the effector proteins of many immune cells in response to antigen recognition. Although secretion shows some similarities to the secretion of specialized granules in other secretory cell types, some aspects of secretory lysosome release appear to be unique to melanocytes and cells of the haemopoietic lineage. Mast cells and platelets have provided excellent models for studying secretion, but recent advances in characterizing the immunological synapse allow a very fine dissection of the secretory process in T lymphocytes. These studies show that secretory lysosomes are secreted from the centre of the talin ring at the synapse. Proper secretion requires a series of Rab and cytoskeletal elements which play critical roles in the specialized secretion of lysosomes in haemopoietic cells. PMID:11380687

The Secret of Future Victories

DTIC Science & Technology

1992-02-01

Copy S of 320 copies AD--A25 0 718 IDA PAPER P-265 3 THE SECRET OF FUTURE VICTORIES Paul F. Gormnan General, USA (Retired) DTIC 05M February 1992 NAY...TYPE AND DATES COVERED IFebruary 1992 Final--June 1991-January 1992 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS The Secret of Future Victories C -MDA...8 2N0-102 IDA PAPER P-2653 THE SECRET OF FUTURE VICTORIES Paul F. Gorman General. LUSA (Retired) February 1992 Approved for public release

Isolated Limb Perfusion of Melphalan With or Without Tumor Necrosis Factor in Treating Patients With Soft Tissue Sarcoma of the Arm or Leg

ClinicalTrials.gov

2012-03-14

Stage IVB Adult Soft Tissue Sarcoma; Stage IIB Adult Soft Tissue Sarcoma; Stage IIC Adult Soft Tissue Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Stage IVA Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma

20 CFR 638.529 - Income taxes.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Income taxes. 638.529 Section 638.529... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.529 Income taxes. The Act... 26, U.S. Code). The Job Corps Director may obtain from tax authorities information regarding taxation...

25 CFR 23.48 - Matching shares and agreements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES INDIAN CHILD WELFARE ACT... matching shares in connection with funds provided under titles IV-B, IV-E and XX of the Social Security Act... enter into agreements with the Secretary of Health and Human Services. The latter Secretary is...

25 CFR 23.48 - Matching shares and agreements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR HUMAN SERVICES INDIAN CHILD WELFARE ACT... matching shares in connection with funds provided under titles IV-B, IV-E and XX of the Social Security Act... enter into agreements with the Secretary of Health and Human Services. The latter Secretary is...

20 CFR 638.519 - Incentives system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Incentives system. 638.519 Section 638.519... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.519 Incentives system. The center operator shall establish and maintain its own incentives system for students in accordance with procedures...

20 CFR 638.534 - Legal services to students.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Legal services to students. 638.534 Section... PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.534 Legal services to... legal representation in criminal and certain civil cases. This shall include assisting students in...

20 CFR 638.534 - Legal services to students.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Legal services to students. 638.534 Section... PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.534 Legal services to... legal representation in criminal and certain civil cases. This shall include assisting students in...

20 CFR 638.523 - Food service.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Food service. 638.523 Section 638.523... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.523 Food service. (a) The center... sufficient in quantity, in accordance with procedures issued by the Job Corps Director. Food shall be...

20 CFR 638.523 - Food service.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Food service. 638.523 Section 638.523... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.523 Food service. (a) The center... sufficient in quantity, in accordance with procedures issued by the Job Corps Director. Food shall be...

20 CFR 638.523 - Food service.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Food service. 638.523 Section 638.523... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.523 Food service. (a) The center... sufficient in quantity, in accordance with procedures issued by the Job Corps Director. Food shall be...

20 CFR 638.511 - Drug use and abuse.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Drug use and abuse. 638.511 Section 638.511... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.511 Drug use and abuse. The Job... and education programs related to drug and alcohol use and abuse. ...

20 CFR 638.511 - Drug use and abuse.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Drug use and abuse. 638.511 Section 638.511... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.511 Drug use and abuse. The Job... and education programs related to drug and alcohol use and abuse. ...

20 CFR 638.511 - Drug use and abuse.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Drug use and abuse. 638.511 Section 638.511... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.511 Drug use and abuse. The Job... and education programs related to drug and alcohol use and abuse. ...

Selumetinib and Cyclosporine in Treating Patients With Advanced Solid Tumors or Advanced or Metastatic Colorectal Cancer

ClinicalTrials.gov

2018-03-23

Recurrent Colorectal Carcinoma; Solid Neoplasm; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

Pembrolizumab and Ziv-aflibercept in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2018-03-08

Adult Solid Neoplasm; Metastatic Melanoma; Metastatic Renal Cell Cancer; Recurrent Colorectal Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

Skylab 3, Saturn S-4B stage falls away from the CM after separation

NASA Image and Video Library

2011-12-13

SL3-114-1634 (July-September 1973) --- Skylab 3, Saturn S-4B (S-IVB) stage falls away from the Command Module (CM) after separation. Earth limb in background, pass over Israel, the Dead Sea and the Mediterranean Sea. Photo credit: NASA

34 CFR 36.2 - Penalty adjustment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... institution of higher education (IHE) to provide information on the cost of higher education to the... and guaranty agencies of Title IV-B of the Higher Education Act of 1965, as amended (HEA), which... penalty of up to $25,000. for an institution of higher education's violation of Title IV of the Higher...

34 CFR 36.2 - Penalty adjustment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... institution of higher education (IHE) to provide information on the cost of higher education to the... and guaranty agencies of Title IV-B of the Higher Education Act of 1965, as amended (HEA), which... penalty of up to $25,000. for an institution of higher education's violation of Title IV of the Higher...

20 CFR 638.513 - Death.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Death. 638.513 Section 638.513 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.513 Death. In each case of student death, the...

20 CFR 638.541 - Job Corps training opportunities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Job Corps training opportunities. 638.541 Section 638.541 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.541 Job Corps...

20 CFR 638.541 - Job Corps training opportunities.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Job Corps training opportunities. 638.541 Section 638.541 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.541 Job Corps...

VSV-hIFNbeta-NIS in Treating Patients With Stage IV or Recurrent Endometrial Cancer

ClinicalTrials.gov

2018-05-09

Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Metastatic Endometrioid Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Recurrent Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IV Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

45 CFR 1355.10 - Scope.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Scope. 1355.10 Section 1355.10 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH... financial participation under titles IV-B and IV-E of the Social Security Act. [61 FR 58653, Nov. 18, 1996] ...

45 CFR 95.601 - Scope and applicability.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Scope and applicability. 95.601 Section 95.601 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GENERAL ADMINISTRATION... IV-B, IV-D, IV-E, XIX or XXI of the Social Security Act. The conditions of approval of this subpart...

45 CFR 1355.10 - Scope.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Scope. 1355.10 Section 1355.10 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH... financial participation under titles IV-B and IV-E of the Social Security Act. [61 FR 58653, Nov. 18, 1996] ...

45 CFR 95.601 - Scope and applicability.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Scope and applicability. 95.601 Section 95.601 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GENERAL ADMINISTRATION... IV-B, IV-D, IV-E, XIX or XXI of the Social Security Act. The conditions of approval of this subpart...

20 CFR 638.507 - Work experience.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Work experience. 638.507 Section 638.507... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.507 Work experience. (a) The center operator shall emphasize and implement programs of work experience for students through center...

20 CFR 638.507 - Work experience.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Work experience. 638.507 Section 638.507... TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.507 Work experience. (a) The center operator shall emphasize and implement programs of work experience for students through center...

45 CFR 1355.21 - Plan requirements for titles IV-E and IV-B.

Code of Federal Regulations, 2013 CFR

2013-10-01

... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON CHILDREN, YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION ASSISTANCE, AND CHILD AND FAMILY SERVICES GENERAL... agency and the Indian Tribe must make available for public review and inspection the Child and Family...

45 CFR 1355.21 - State plan requirements for titles IV-E and IV-B.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON CHILDREN, YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION ASSISTANCE, AND CHILD AND FAMILY SERVICES... and the Indian Tribe must make available for public review and inspection the Child and Family...

20 CFR 638.535 - Voting rights.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Voting rights. 638.535 Section 638.535 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.535 Voting rights. The Job Corps...

20 CFR 638.535 - Voting rights.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Voting rights. 638.535 Section 638.535 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.535 Voting rights. The Job Corps...

20 CFR 638.601 - Applied VST budgeting.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Applied VST budgeting. 638.601 Section 638.601 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Applied Vocational Skills Training (VST) § 638.601...

20 CFR 638.601 - Applied VST budgeting.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Applied VST budgeting. 638.601 Section 638.601 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Applied Vocational Skills Training (VST) § 638.601...

Atezolizumab and Bevacizumab in Treating Patients With Recurrent, Persistent, or Metastatic Cervical Cancer

ClinicalTrials.gov

2018-04-20

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IV Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7