Isolation and Characterization of Mms-Sensitive Mutants of SACCHAROMYCES CEREVISIAE
Prakash, Louise; Prakash, Satya
1977-01-01
We have isolated mutants sensitive to methyl methanesulfonate (MMS) in Saccharomyces cerevisiae. Alleles of rad1, rad4, rad6, rad52, rad55 and rad57 were found among these mms mutants. Twenty-nine of the mms mutants which complement the existing radiation-sensitive (rad and rev ) mutants belong to 22 new complementation groups. Mutants from five complementation groups are sensitive only to MMS. Mutants of 11 complementation groups are sensitive to UV or X rays in addition to MMS, mutants of six complementation groups are sensitive to all three agents. The cross-sensitivities of these mms mutants to UV and X rays are discussed in terms of their possible involvement in DNA repair. Sporulation is reduced or absent in homozygous diploids of mms mutants from nine complementation groups. PMID:195865
a/alpha-specific effect on the mms3 mutation on ultraviolet mutagenesis in Saccharomyces cerevisiae.
Martin, P; Prakash, L; Prakash, S
1981-05-01
A new gene involved in error-prone repair of ultraviolet (UV) damage has been identified in Saccharomyces cerevisiae by the mms3-1 mutation. UV-induced reversion is reduced in diploids that are homozygous for mms3-1, only if they are also heterozygous (MATa/MAT alpha) at the mating type locus. The mms3-1 mutation has no effect on UV-induced reversion either in haploids or MATa/MATa or MAT alpha/MAT alpha diploids. The mutation confers sensitivity to UV and methyl methane sulfonate in both haploids and diploids. Even though mutation induction by UV is restored to wild-type levels in MATa/MATa mms3-1/mms3-1 or MAT alpha/MAT alpha mms3-1/mms3-1 diploids, such strains still retain sensitivity to the lethal effects of UV. Survival after UV irradiation in mms3-1 rad double mutant combinations indicates that mms3-1 is epistatic to rad6-1 whereas non-epistatic interactions are observed with rad3 and rad52 mutants. When present in the homozygous state in MATa/MAT alpha his1-1/his1-315 heteroallelic diploids, mms3-1 was found to lower UV-induced mitotic recombination.
Odagiri, Nao; Seki, Masayuki; Onoda, Fumitoshi; Yoshimura, Akari; Watanabe, Sei; Enomoto, Takemi
2003-03-01
MMS4 of Saccharomyces cerevisiae was originally identified as the gene responsible for one of the collection of methyl methanesulfonate (MMS)-sensitive mutants, mms4. Recently it was identified as a synthetic lethal gene with an SGS1 mutation. Epistatic analyses revealed that MMS4 is involved in a pathway leading to homologous recombination requiring Rad52 or in the recombination itself, in which SGS1 is also involved. MMS sensitivity of mms4 but not sgs1, was suppressed by introducing a bacterial Holliday junction (HJ) resolvase, RusA. The frequencies of spontaneously occurring unequal sister chromatid recombination (SCR) and loss of marker in the rDNA in haploid mms4 cells and interchromosomal recombination between heteroalleles in diploid mms4 cells were essentially the same as those of wild-type cells. Although UV- and MMS-induced interchromosomal recombination was defective in sgs1 diploid cells, hyper-induction of interchromosomal recombination was observed in diploid mms4 cells, indicating that the function of Mms4 is dispensable for this type of recombination.
Stumpf, Jeffrey D.; Copeland, William C.
2014-01-01
Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutations affecting conserved regions of the mtDNA polymerase, Mip1, in the presence of the wild type Mip1. Mutant frequency arising from mtDNA base substitutions that confer erythromycin resistance and deletions between 21-nucleotide direct repeats was determined. Previously, increased mutagenesis was observed in strains encoding mutant variants that were insufficient to maintain mtDNA and that were not expected to reduce polymerase fidelity or exonuclease proofreading. Increased mutagenesis could be explained by mutant variants stalling the replication fork, thereby predisposing the template DNA to irreparable damage that is bypassed with poor fidelity. This hypothesis suggests that the exogenous base-alkylating agent, methyl methanesulfonate (MMS), would further increase mtDNA mutagenesis. Mitochondrial mutagenesis associated with MMS exposure was increased up to 30-fold in mip1 mutants containing disease-associated alterations that affect polymerase activity. Disrupting exonuclease activity of mutant variants was not associated with increased spontaneous mutagenesis compared with exonuclease-proficient alleles, suggesting that most or all of the mtDNA was replicated by wild type Mip1. A novel subset of C to G transversions was responsible for about half of the mutants arising after MMS exposure implicating error-prone bypass of methylated cytosines as the predominant mutational mechanism. Exposure to MMS does not disrupt exonuclease activity that suppresses deletions between 21-nucleotide direct repeats, suggesting the MMS-induce mutagenesis is not explained by inactivated exonuclease activity. Further, trace amounts of CdCl2 inhibit mtDNA replication but suppresses MMS-induced mutagenesis. These results suggest a novel mechanism wherein mutations that lead to hypermutation by DNA base-damaging agents and associate with mitochondrial disease may contribute to previously unexplained phenomena, such as the wide variation of age of disease onset and acquired mitochondrial toxicities. PMID:25340760
Stumpf, Jeffrey D; Copeland, William C
2014-10-01
Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutations affecting conserved regions of the mtDNA polymerase, Mip1, in the presence of the wild type Mip1. Mutant frequency arising from mtDNA base substitutions that confer erythromycin resistance and deletions between 21-nucleotide direct repeats was determined. Previously, increased mutagenesis was observed in strains encoding mutant variants that were insufficient to maintain mtDNA and that were not expected to reduce polymerase fidelity or exonuclease proofreading. Increased mutagenesis could be explained by mutant variants stalling the replication fork, thereby predisposing the template DNA to irreparable damage that is bypassed with poor fidelity. This hypothesis suggests that the exogenous base-alkylating agent, methyl methanesulfonate (MMS), would further increase mtDNA mutagenesis. Mitochondrial mutagenesis associated with MMS exposure was increased up to 30-fold in mip1 mutants containing disease-associated alterations that affect polymerase activity. Disrupting exonuclease activity of mutant variants was not associated with increased spontaneous mutagenesis compared with exonuclease-proficient alleles, suggesting that most or all of the mtDNA was replicated by wild type Mip1. A novel subset of C to G transversions was responsible for about half of the mutants arising after MMS exposure implicating error-prone bypass of methylated cytosines as the predominant mutational mechanism. Exposure to MMS does not disrupt exonuclease activity that suppresses deletions between 21-nucleotide direct repeats, suggesting the MMS-induce mutagenesis is not explained by inactivated exonuclease activity. Further, trace amounts of CdCl2 inhibit mtDNA replication but suppresses MMS-induced mutagenesis. These results suggest a novel mechanism wherein mutations that lead to hypermutation by DNA base-damaging agents and associate with mitochondrial disease may contribute to previously unexplained phenomena, such as the wide variation of age of disease onset and acquired mitochondrial toxicities.
Characterization of a Novel MMS-Sensitive Allele of Schizosaccharomyces pombe mcm4+
Ranatunga, Nimna S.; Forsburg, Susan L.
2016-01-01
The minichromosome maintenance (MCM) complex is the conserved helicase motor of the eukaryotic replication fork. Mutations in the Mcm4 subunit are associated with replication stress and double strand breaks in multiple systems. In this work, we characterize a new temperature-sensitive allele of Schizosaccharomyces pombe mcm4+. Uniquely among known mcm4 alleles, this mutation causes sensitivity to the alkylation damaging agent methyl methanesulfonate (MMS). Even in the absence of treatment or temperature shift, mcm4-c106 cells show increased repair foci of RPA and Rad52, and require the damage checkpoint for viability, indicating genome stress. The mcm4-c106 mutant is synthetically lethal with mutations disrupting fork protection complex (FPC) proteins Swi1 and Swi3. Surprisingly, we found that the deletion of rif1+ suppressed the MMS-sensitive phenotype without affecting temperature sensitivity. Together, these data suggest that mcm4-c106 destabilizes replisome structure. PMID:27473316
Xu, Panglian; Yuan, Dongke; Liu, Ming; Li, Chunxin; Liu, Yiyang; Zhang, Shengchun; Yao, Nan; Yang, Chengwei
2013-04-01
Plants maintain stem cells in meristems to sustain lifelong growth; these stem cells must have effective DNA damage responses to prevent mutations that can propagate to large parts of the plant. However, the molecular links between stem cell functions and DNA damage responses remain largely unexplored. Here, we report that the small ubiquitin-related modifier E3 ligase AtMMS21 (for methyl methanesulfonate sensitivity gene21) acts to maintain the root stem cell niche by mediating DNA damage responses in Arabidopsis (Arabidopsis thaliana). Mutation of AtMMS21 causes defects in the root stem cell niche during embryogenesis and postembryonic stages. AtMMS21 is essential for the proper expression of stem cell niche-defining transcription factors. Moreover, mms21-1 mutants are hypersensitive to DNA-damaging agents, have a constitutively increased DNA damage response, and have more DNA double-strand breaks (DSBs) in the roots. Also, mms21-1 mutants exhibit spontaneous cell death within the root stem cell niche, and treatment with DSB-inducing agents increases this cell death, suggesting that AtMMS21 is required to prevent DSB-induced stem cell death. We further show that AtMMS21 functions as a subunit of the STRUCTURAL MAINTENANCE OF CHROMOSOMES5/6 complex, an evolutionarily conserved chromosomal ATPase required for DNA repair. These data reveal that AtMMS21 acts in DSB amelioration and stem cell niche maintenance during Arabidopsis root development.
The recX gene product is involved in the SOS response in Herbaspirillum seropedicae.
Galvão, Carolina W; Pedrosa, Fábio O; Souza, Emanuel M; Yates, M Geoffrey; Chubatsu, Leda S; Steffens, Maria Berenice R
2003-02-01
The recA and the recX genes of Herbaspirillum seropedicae were sequenced. The recX is located 359 bp downstream from recA. Sequence analysis indicated the presence of a putative operator site overlapping a probable sigma70-dependent promoter upstream of recA and a transcription terminator downstream from recX, with no apparent promoter sequence in the intergenic region. Transcriptional analysis using lacZ promoter fusions indicated that recA expression increased three- to fourfold in the presence of methyl methanesulfonate (MMS). The roles of recA and recX genes in the SOS response were determined from studies of chromosomal mutants. The recA mutant showed the highest sensitivity to MMS and UV, and the recX mutant had an intermediate sensitivity, compared with the wild type (SMR1), confirming the essential role of the RecA protein in cell viability in the presence of mutagenic agents and also indicating a role for RecX in the SOS response.
van Heemst, D; Swart, K; Holub, E F; van Dijk, R; Offenberg, H H; Goosen, T; van den Broek, H W; Heyting, C
1997-05-01
We have cloned the uvsC gene of Aspergillus nidulans by complementation of the A. nidulans uvsC114 mutant. The predicted protein UVSC shows 67.4% sequence identity to the Saccharomyces cerevisiae Rad51 protein and 27.4% sequence identity to the Escherichia coli RecA protein. Transcription of uvsC is induced by methyl-methane sulphonate (MMS), as is transcription of RAD51 of yeast. Similar levels of uvsC transcription were observed after MMS induction in a uvsC+ strain and the uvsC114 mutant. The coding sequence of the uvsC114 allele has a deletion of 6 bp, which results in deletion of two amino acids and replacement of one amino acid in the translation product. In order to gain more insight into the biological function of the uvsC gene, a uvsC null mutant was constructed, in which the entire uvsC coding sequence was replaced by a selectable marker gene. Meiotic and mitotic phenotypes of a uvsC+ strain, the uvsC114 mutant and the uvsC null mutant were compared. The uvsC null mutant was more sensitive to both UV and MMS than the uvsC114 mutant. The uvsC114 mutant arrested in meiotic prophase-I. The uvsC null mutant arrested at an earlier stage, before the onset of meiosis. One possible interpretation of these meiotic phenotypes is that the A. nidulans homologue of Rad51 of yeast has a role both in the specialized processes preceding meiosis and in meiotic prophase I.
Interaction of caffeine with the SOS response pathway in Escherichia coli.
Whitney, Alyssa K; Weir, Tiffany L
2015-01-01
Previous studies have highlighted the antimicrobial activity of caffeine, both individually and in combination with other compounds. A proposed mechanism for caffeine's antimicrobial effects is inhibition of bacterial DNA repair pathways. The current study examines the influence of sub-lethal caffeine levels on the growth and morphology of SOS response pathway mutants of Escherichia coli. Growth inhibition after treatment with caffeine and methyl methane sulfonate (MMS), a mutagenic agent, was determined for E. coli mutants lacking key genes in the SOS response pathway. The persistence of caffeine's effects was explored by examining growth and morphology of caffeine and MMS-treated bacterial isolates in the absence of selective pressure. Caffeine significantly reduced growth of E. coli recA- and uvrA-mutants treated with MMS. However, there was no significant difference in growth between umuC-isolates treated with MMS alone and MMS in combination with caffeine after 48 h of incubation. When recA-isolates from each treatment group were grown in untreated medium, bacterial isolates that had been exposed to MMS or MMS with caffeine showed increased growth relative to controls and caffeine-treated isolates. Morphologically, recA-isolates that had been treated with caffeine and both caffeine and MMS together had begun to display filamentous growth. Caffeine treatment further reduced growth of recA- and uvrA-mutants treated with MMS, despite a non-functional SOS response pathway. However, addition of caffeine had very little effect on MMS inhibition of umuC-mutants. Thus, growth inhibition of E. coli with caffeine treatment may be driven by caffeine interaction with UmuC, but also appears to induce damage by additional mechanisms as evidenced by the additive effects of caffeine in recA- and uvrA-mutants.
PSO4: a novel gene involved in error-prone repair in Saccharomyces cerevisiae.
Henriques, J A; Vicente, E J; Leandro da Silva, K V; Schenberg, A C
1989-09-01
The haploid xs9 mutant, originally selected for on the basis of a slight sensitivity to the lethal effect of X-rays, was found to be extremely sensitive to inactivation by 8-methoxypsoralen (8MOP) photoaddition, especially when cells are treated in the G2 phase of the cell cycle. As the xs9 mutation showed no allelism with any of the 3 known pso mutations, it was now given the name of pso4-1. Regarding inactivation, the pso4-1 mutant is also sensitive to mono- (HN1) or bi-functional (HN2) nitrogen mustards, it is slightly sensitive to 254 nm UV radiation (UV), and shows nearly normal sensitivity to 3-carbethoxypsoralen (3-CPs) photoaddition or methyl methanesulfonate (MMS). Regarding mutagenesis, the pso4-1 mutation completely blocks reverse and forward mutations induced by either 8MOP or 3CPs photoaddition, or by gamma-rays. In the cases of UV, HN1, HN2 or MMS treatments, while reversion induction is still completely abolished, forward mutagenesis is only partially inhibited for UV, HN1, or MMS, and it is unaffected for HN2. Besides severely inhibiting induced mutagenesis, the pso4-1 mutation was found to be semi-dominant, to block sporulation, to abolish the diploid resistance effect, and to block induced mitotic recombination, which indicates that the PSO4 gene is involved in a recombinational pathway of error-prone repair, comparable to the E. coli SOS repair pathway.
Eckardt-Schupp, Friederike; Siede, Wolfram; Game, John C.
1987-01-01
The moderately UV- and X-ray-sensitive mutant of Saccharomyces cerevisiae originally designated rs1 complements all rad and mms mutants available. Therefore, the new nomination rad24-1 according to the RAD nomenclature is suggested. RAD24 maps on chromosome V, close to RAD3 (1.3 cM). In order to associate the RAD24 gene with one of the three repair pathways, double mutants of rad24 and various representative genes of each pathway were constructed. The UV and X-ray sensitivities of the double mutants compared to the single mutants indicate that RAD24 is involved in excision repair of UV damage (RAD3 epistasis group), as well as in recombination repair of UV and X-ray damage (RAD52 epistasis group). Properties of the mutant are discussed which hint at the control of late steps in the pathways. PMID:3549445
Piening, Brian D.; Huang, Dongqing; Paulovich, Amanda G.
2013-01-01
Tel1 is the budding yeast ortholog of the mammalian tumor suppressor and DNA damage response (DDR) kinase ATM. However, tel1-Δ cells, unlike ATM-deficient cells, do not exhibit sensitivity to DNA-damaging agents, but do display shortened (but stably maintained) telomere lengths. Neither the extent to which Tel1p functions in the DDR nor the mechanism by which Tel1 contributes to telomere metabolism is well understood. To address the first question, we present the results from a comprehensive genome-wide screen for genetic interactions with tel1-Δ that cause sensitivity to methyl methanesulfonate (MMS) and/or ionizing radiation, along with follow-up characterizations of the 13 interactions yielded by this screen. Surprisingly, many of the tel1-Δ interactions that confer DNA damage sensitivity also exacerbate the short telomere phenotype, suggesting a connection between these two phenomena. Restoration of normal telomere length in the tel1-Δ xxx-Δ mutants results in only minor suppression of the DNA damage sensitivity, demonstrating that the sensitivity of these mutants must also involve mechanisms independent of telomere length. In support of a model for increased replication stress in the tel1-Δ xxx-Δ mutants, we show that depletion of dNTP pools through pretreatment with hydroxyurea renders tel1-Δ cells (but not wild type) MMS-sensitive, demonstrating that, under certain conditions, Tel1p does indeed play a critical role in the DDR. PMID:23378069
da Silva Vasconcelos, Eliton; de Lima, Vanderlei Aparecido; Goto, Leandro Seiji; Cruz-Hernández, Isara Lourdes; Hokka, Carlos Osamu
2013-01-01
Clavulanic acid (CA) is a powerful inhibitor of the beta-lactamases, enzymes produced by bacteria resistants to penicillin and cefalosporin. This molecule is produced industrially by strains of Streptomyces clavuligerus in complex media which carbon and nitrogen resources are supplied by inexpensive compounds still providing high productivity. The genetic production improvement using physical and chemical mutagenic agents is an important strategy in programs of industrial production development of bioactive metabolites. However, parental strains are susceptible to loss of their original productivity due genetic instability phenomenona. In this work, some S. clavuligerus mutant strains obtained by treatment with UV light and with MMS are compared with the wild type (Streptomyces clavuligerus ATCC 27064). The results indicated that the random mutations originated some strains with different phenotypes, most divergent demonstrated by the mutants strains named AC116, MMS 150 and MMS 54, that exhibited lack of pigmentation in their mature spores. Also, the strain MMS 150 presented a larger production of CA when cultivated in semi-synthetics media. Using other media, the wild type strain obtained a larger CA production. Besides, using the modifed complex media the MMS 150 strain showed changes in its lipolitic activity and a larger production of CA. The studies also allowed finding the best conditions for a lipase activity exhibited by wild type S. clavuligerus and the MMS150 mutant. PMID:24688492
Chauhan, Priyanka
2018-01-01
ABSTRACT Previously we had developed a triple gene mutant of Mycobacterium tuberculosis (MtbΔmms) harboring disruption in three genes, namely mptpA, mptpB and sapM. Though vaccination with MtbΔmms strain induced protection in the lungs of guinea pigs, the mutant strain failed to control the hematogenous spread of the challenge strain to the spleen. Additionally, inoculation with MtbΔmms resulted in some pathological damage to the spleens in the early phase of infection. In order to generate a strain that overcomes the pathology caused by MtbΔmms in spleen of guinea pigs and controls dissemination of the challenge strain, MtbΔmms was genetically modified by disrupting bioA gene to generate MtbΔmmsb strain. Further, in vivo attenuation of MtbΔmmsb was evaluated and its protective efficacy was assessed against virulent M. tuberculosis challenge in guinea pigs. MtbΔmmsb mutant strain was highly attenuated for growth and virulence in guinea pigs. Vaccination with MtbΔmmsb mutant generated significant protection in comparison to sham-immunized animals at 4 and 12 weeks post-infection in lungs and spleen of infected animals. However, the protection imparted by MtbΔmmsb was significantly less in comparison to BCG immunized animals. This study indicates the importance of attenuated multiple gene deletion mutants of M. tuberculosis for generating protection against tuberculosis. PMID:29242198
Maeda, Daisuke; Seki, Masayuki; Onoda, Fumitoshi; Branzei, Dana; Kawabe, Yoh-Ichi; Enomoto, Takemi
2004-03-04
Ubc9 is an enzyme involved in the conjugation of small ubiquitin related modifier (SUMO) to target proteins. A Saccharomyces cerevisiae ubc9 temperature sensitive (ts) mutant showed higher sensitivity to various DNA damaging agents such as methylmethanesulfonate (MMS) and UV at a semi-permissive temperature than wild-type cells. The sensitivity of ubc9ts cells was not suppressed by the introduction of a mutated UBC9 gene, UBC9-C93S, whose product is unable to covalently bind to SUMO and consequently fails to conjugate SUMO to target proteins. Diploid ubc9ts cells were more sensitive to various DNA damaging agents than haploid ubc9ts cells suggesting the involvement of homologous recombination in the sensitivity of ubc9ts cells. The frequency of interchromosomal recombination between heteroalleles, his1-1/his1-7 loci, in wild-type cells was remarkably increased upon exposure to MMS or UV. Although the frequency of spontaneous interchromosomal recombination between the heteroalleles in ubc9ts cells was almost the same as that of wild-type cells, no induction of interchromosomal recombination was observed in ubc9ts cells upon exposure to MMS or UV. Copyright 2003 Elsevier B.V.
Melnik, Andre; Wilson-Zbinden, Caroline; Schellhaas, René; Kastner, Lisa; Piwko, Wojciech; Dees, Martina; Picotti, Paola; Maric, Marija; Labib, Karim; Luke, Brian; Peter, Matthias
2016-01-01
Faithful DNA replication and repair requires the activity of cullin 4-based E3 ubiquitin ligases (CRL4), but the underlying mechanisms remain poorly understood. The budding yeast Cul4 homologue, Rtt101, in complex with the linker Mms1 and the putative substrate adaptor Mms22 promotes progression of replication forks through damaged DNA. Here we characterized the interactome of Mms22 and found that the Rtt101Mms22 ligase associates with the replisome progression complex during S-phase via the amino-terminal WD40 domain of Ctf4. Moreover, genetic screening for suppressors of the genotoxic sensitivity of rtt101Δ cells identified a cluster of replication proteins, among them a component of the fork protection complex, Mrc1. In contrast to rtt101Δ and mms22Δ cells, mrc1Δ rtt101Δ and mrc1Δ mms22Δ double mutants complete DNA replication upon replication stress by facilitating the repair/restart of stalled replication forks using a Rad52-dependent mechanism. Our results suggest that the Rtt101Mms22 E3 ligase does not induce Mrc1 degradation, but specifically counteracts Mrc1’s replicative function, possibly by modulating its interaction with the CMG (Cdc45-MCM-GINS) complex at stalled forks. PMID:26849847
Acevedo-Torres, Karina; Fonseca-Williams, Sharon; Ayala-Torres, Sylvette; Torres-Ramos, Carlos A.
2010-01-01
The Saccharomyces cerevisiae APN1 gene that participates in base excision repair has been localized both in the nucleus and the mitochondria. APN1 deficient cells (apn1Δ) show increased mutation frequencies in mitochondrial DNA (mtDNA) suggesting that APN1 is also important for mtDNA stability. To understand APN1-dependent mtDNA repair processes we studied the formation and repair of mtDNA lesions in cells exposed to methyl methanesulfonate (MMS). We show that MMS induces mtDNA damage in a dose-dependent fashion and that deletion of the APN1 gene enhances the susceptibility of mtDNA to MMS. Repair kinetic experiments demonstrate that in wild-type cells (WT) it takes 4 hr to repair the damage induced by 0.1% MMS, whereas in the apn1Δ strain there is a lag in mtDNA repair that results in significant differences in the repair capacity between the two yeast strains. Analysis of lesions in nuclear DNA (nDNA) after treatment with 0.1% MMS shows a significant difference in the amount of nDNA lesions between WT and apn1Δ cells. Interestingly, comparisons between nDNA and mtDNA damage show that nDNA is more sensitive to the effects of MMS treatment. However, both strains are able to repair the nDNA lesions, contrary to mtDNA repair, which is compromised in the apn1Δ mutant strain. Therefore, although nDNA is more sensitive than mtDNA to the effects of MMS, deletion of APN1 has a stronger phenotype in mtDNA repair than in nDNA. These results highlight the prominent role of APN1 in the repair of environmentally induced mtDNA damage. PMID:19197988
Koch, Melissa R.; House, Nealia C. M.; Cosetta, Casey M.; Jong, Robyn M.; Salomon, Christelle G.; Joyce, Cailin E.; Philips, Elliot A.; Su, Xiaofeng A.; Freudenreich, Catherine H.
2018-01-01
CAG/CTG trinucleotide repeats are unstable sequences that are difficult to replicate, repair, and transcribe due to their structure-forming nature. CAG repeats strongly position nucleosomes; however, little is known about the chromatin remodeling needed to prevent repeat instability. In a Saccharomyces cerevisiae model system with CAG repeats carried on a YAC, we discovered that the chromatin remodeler Isw1 is required to prevent CAG repeat expansions during transcription. CAG repeat expansions in the absence of Isw1 were dependent on both transcription-coupled repair (TCR) and base-excision repair (BER). Furthermore, isw1∆ mutants are sensitive to methyl methanesulfonate (MMS) and exhibit synergistic MMS sensitivity when combined with BER or TCR pathway mutants. We conclude that CAG expansions in the isw1∆ mutant occur during a transcription-coupled excision repair process that involves both TCR and BER pathways. We observed increased RNA polymerase II (RNAPII) occupancy at the CAG repeat when transcription of the repeat was induced, but RNAPII binding did not change in isw1∆ mutants, ruling out a role for Isw1 remodeling in RNAPII progression. However, nucleosome occupancy over a transcribed CAG tract was altered in isw1∆ mutants. Based on the known role of Isw1 in the reestablishment of nucleosomal spacing after transcription, we suggest that a defect in this function allows DNA structures to form within repetitive DNA tracts, resulting in inappropriate excision repair and repeat-length changes. These results establish a new function for Isw1 in directly maintaining the chromatin structure at the CAG repeat, thereby limiting expansions that can occur during transcription-coupled excision repair. PMID:29305386
Lee, Ji Young; Jun, Do Youn; Park, Ju Eun; Kwon, Gi Hyun; Kim, Jong-Sik; Kim, Young Ho
2017-03-28
To examine the pro-apoptotic role of the human ortholog (YPEL5) of the Drosophila Yippee protein, the cell viability of Saccharomyces cerevisiae mutant strain with deleted MOH1 , the yeast ortholog, was compared with that of the wild-type (WT)- MOH1 strain after exposure to different apoptogenic stimulants, including UV irradiation, methyl methanesulfonate (MMS), camptothecin (CPT), heat shock, and hyperosmotic shock. The moh1 Δ mutant exhibited enhanced cell viability compared with the WT- MOH1 strain when treated with lethal UV irradiation, 1.8 mM MMS, 100 µ CPT, heat shock at 50°C, or 1.2 M KCl. At the same time, the level of Moh1 protein was commonly up-regulated in the WT- MOH1 strain as was that of Ynk1 protein, which is known as a marker for DNA damage. Although the enhanced UV resistance of the moh1 Δ mutant largely disappeared following transformation with the yeast MOH1 gene or one of the human YPEL1-YPEL5 genes, the transformant bearing pYES2- YPEL5 was more sensitive to lethal UV irradiation and its UV sensitivity was similar to that of the WT- MOH1 strain. Under these conditions, the UV irradiation-induced apoptotic events, such as FITC-Annexin V stainability, mitochondrial membrane potential (ΔΨm) loss, and metacaspase activation, occurred to a much lesser extent in the moh1 Δ mutant compared with the WT- MOH1 strain and the mutant strain bearing pYES2- MOH1 or pYES2- YPEL5 . These results demonstrate the functional conservation between yeast Moh1 and human YPEL5, and their involvement in mitochondria-dependent apoptosis induced by DNA damage.
Kovtunov, E A; Shelud'ko, A V; Chernyshova, M P; Petrova, L P; Katsy, E I
2013-11-01
Bacteria Azospirillum brasilense have mixed flagellation: in addition to the polar flagellum, numerous lateral flagella are formed in their cells on medium with increased density. Flagella determine the active swimming and swarming capacities of azospirilla. Using A. brasilense Sp245 as an example, we showed that the Omegon-Km artificial transposon insertion into the chromosomal gene for 3-hydroxyisobutyrate dehydrogenase (mmsB) was concurrent with the appearance of significant defects in the formation of polar flagella and with the paralysis of lateral flagella. The Sp245 mutant with the Omegon insertion into the plasmid AZOBR_p1-borne gene for 3-oxoacyl-[acyl-carrier protein]-reductase (fabG) showed the complete loss of flagella and the swarming capacity, as well as significant defects in polar flagellar assembly (though some cells are still motile in liquid medium). The viability of the A. brasilense Sp245 mutants with the Omegon insertion into the mmsB or fabG gene was not reduced. No considerable differences in the fatty acid composition of whole cell lipid extracts were found for the A. brasilense Sp245 strain and its mmsB and fabG mutants.
Bennett, Richard A. O.
1999-01-01
The recently sequenced Saccharomyces cerevisiae genome was searched for a gene with homology to the gene encoding the major human AP endonuclease, a component of the highly conserved DNA base excision repair pathway. An open reading frame was found to encode a putative protein (34% identical to the Schizosaccharomyces pombe eth1+ [open reading frame SPBC3D6.10] gene product) with a 347-residue segment homologous to the exonuclease III family of AP endonucleases. Synthesis of mRNA from ETH1 in wild-type cells was induced sixfold relative to that in untreated cells after exposure to the alkylating agent methyl methanesulfonate (MMS). To investigate the function of ETH1, deletions of the open reading frame were made in a wild-type strain and a strain deficient in the known yeast AP endonuclease encoded by APN1. eth1 strains were not more sensitive to killing by MMS, hydrogen peroxide, or phleomycin D1, whereas apn1 strains were ∼3-fold more sensitive to MMS and ∼10-fold more sensitive to hydrogen peroxide than was the wild type. Double-mutant strains (apn1 eth1) were ∼15-fold more sensitive to MMS and ∼2- to 3-fold more sensitive to hydrogen peroxide and phleomycin D1 than were apn1 strains. Elimination of ETH1 in apn1 strains also increased spontaneous mutation rates 9- or 31-fold compared to the wild type as determined by reversion to adenine or lysine prototrophy, respectively. Transformation of apn1 eth1 cells with an expression vector containing ETH1 reversed the hypersensitivity to MMS and limited the rate of spontaneous mutagenesis. Expression of ETH1 in a dut-1 xthA3 Escherichia coli strain demonstrated that the gene product functionally complements the missing AP endonuclease activity. Thus, in apn1 cells where the major AP endonuclease activity is missing, ETH1 offers an alternate capacity for repair of spontaneous or induced damage to DNA that is normally repaired by Apn1 protein. PMID:10022867
Zhang, Chao; Li, Zhouquan; Zhang, Xiaohua; Yuan, Li; Dai, Heping; Xiao, Wei
2016-01-01
Transcriptomic profiles are generated by comparing wild-type and the yeast yap1 mutant to various chemicals in an attempt to establish a correlation between this gene mutation and chemical exposure. Test chemicals include ClonNAT as a non-genotoxic agent, methyl methanesulphonate (MMS) as an alkylating agent, tert-butyl hydroperoxide (t-BHP) as an oxidative agent and the mixture of t-BHP and MMS to reflect complex natural exposure. Differentially expressed genes (DEGs) were identified and specific DEGs were obtained by excluding overlapping DEGs with the control group. In the MMS exposure group, deoxyribonucleotide biosynthetic processes were upregulated, while oxidation-reduction processes were downregulated. In the t-BHP exposure group, metabolic processes were upregulated while peroxisome and ion transport pathways were downregulated. In the mixture exposure group, the proteasome pathway was upregulated, while the aerobic respiration was downregulated. Homologue analysis of DEGs related to human diseases showed that many of DEGs were linked to cancer, ageing and neuronal degeneration. These observations confirm that the yap1 mutant is more sensitive to chemicals than wild-type cells and that the susceptible individuals carrying the YAP1-like gene defect may enhance risk to chemical exposure. Hence, this study offers a novel approach to environmental risk assessment, based on the genetic backgrounds of susceptible individuals. Copyright © 2015 John Wiley & Sons, Ltd.
Lack of chemically induced mutation in repair-deficient mutants of yeast.
Prakash, L
1974-12-01
Two genes, rad6 and rad9, that confer radiation sensitivity in the yeast Saccharomyces cerevisiae also greatly reduce the frequency of chemically-induced reversions of a tester mutant cyc1-131, which is a chain initiation mutant in the structural gene determining iso-1-cytochrome c. Mutations induced by ethyl methanesulfonate (EMS), diethyl sulfate (DES), methyl methanesulfonate (MMS), dimethyl sulfate (DMS), nitroquinoline oxide (NQO), nitrosoguanidine (NTG), nitrogen mustard (HN2), beta-propiolactone, and tritiated uridine, as well as mutations induced by ultraviolet light (UV) and ionizing radiation were greatly diminished in strains homozygous for either the rad6 or rad9 gene. Nitrous acid and nitrosoimidazolidone (NIL), on the other hand, were highly mutagenic in these repair-deficient mutants, and at low doses, these mutagens acted with about the same efficiency as in the normal RAD strain. At high doses of either nitrous acid or NIL, however, reversion frequencies were significantly reduced in the two rad mutants compared to normal strains. Although both rad mutants are immutable to about the same extent, the rad9 strains tend to be less sensitive to the lethal effect of chemical mutagens than rad6 strains. It is concluded that yeast requires a functional repair system for mutation induction by chemical agents.
Functions of Fun30 Chromatin Remodeler in Regulating Cellular Resistance to Genotoxic Stress
Bi, Xin; Yu, Qun; Siler, Jasmine; Li, Chong; Khan, Ali
2015-01-01
The Saccharomyces cerevisiae Fun30 chromatin remodeler has recently been shown to facilitate long-range resection of DNA double strand break (DSB) ends, which proceeds homologous recombination (HR). This is believed to underlie the role of Fun30 in promoting cellular resistance to DSB inducing agent camptothecin. We show here that Fun30 also contributes to cellular resistance to genotoxins methyl methanesulfonate (MMS) and hydroxyurea (HU) that can stall the progression of DNA replication. We present evidence implicating DNA end resection in Fun30-dependent MMS-resistance. On the other hand, we show that Fun30 deletion suppresses the MMS- and HU-sensitivity of cells lacking the Rad5/Mms2/Ubc13-dependent error-free DNA damage tolerance mechanism. This suppression is not the result of a reduction in DNA end resection, and is dependent on the key HR component Rad51. We further show that Fun30 negatively regulates the recovery of rad5Δ mutant from MMS induced G2/M arrest. Therefore, Fun30 has two functions in DNA damage repair: one is the promotion of cellular resistance to genotoxic stress by aiding in DNA end resection, and the other is the negative regulation of a Rad51-dependent, DNA end resection-independent mechanism for countering replicative stress. The latter becomes manifest when Rad5 dependent DNA damage tolerance is impaired. In addition, we find that the putative ubiquitin-binding CUE domain of Fun30 serves to restrict the ability of Fun30 to hinder MMS- and HU-tolerance in the absence of Rad5. PMID:25806814
Wit, Niek; Buoninfante, Olimpia Alessandra; van den Berk, Paul C.M.; Jansen, Jacob G.; Hogenbirk, Marc A.; de Wind, Niels; Jacobs, Heinz
2015-01-01
Translesion synthesis (TLS) provides a highly conserved mechanism that enables DNA synthesis on a damaged template. TLS is performed by specialized DNA polymerases of which polymerase (Pol) κ is important for the cellular response to DNA damage induced by benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), ultraviolet (UV) light and the alkylating agent methyl methanesulfonate (MMS). As TLS polymerases are intrinsically error-prone, tight regulation of their activity is required. One level of control is provided by ubiquitination of the homotrimeric DNA clamp PCNA at lysine residue 164 (PCNA-Ub). We here show that Polκ can function independently of PCNA modification and that Polη can function as a backup during TLS of MMS-induced lesions. Compared to cell lines deficient for PCNA modification (PcnaK164R) or Polκ, double mutant cell lines display hypersensitivity to MMS but not to BPDE or UV-C. Double mutant cells also displayed delayed post-replicative TLS, accumulate higher levels of replication stress and delayed S-phase progression. Furthermore, we show that Polη and Polκ are redundant in the DNA damage bypass of MMS-induced DNA damage. Taken together, we provide evidence for PCNA-Ub-independent activation of Polκ and establish Polη as an important backup polymerase in the absence of Polκ in response to MMS-induced DNA damage. PMID:25505145
Legrand, Melanie; Chan, Christine L.; Jauert, Peter A.; Kirkpatrick, David T.
2011-01-01
Genome rearrangements, a common feature of Candida albicans isolates, are often associated with the acquisition of antifungal drug resistance. In Saccharomyces cerevisiae, perturbations in the S-phase checkpoints result in the same sort of Gross Chromosomal Rearrangements (GCRs) observed in C. albicans. Several proteins are involved in the S. cerevisiae cell cycle checkpoints, including Mec1p, a protein kinase of the PIKK (phosphatidyl inositol 3-kinase-like kinase) family and the central player in the DNA damage checkpoint. Sgs1p, the ortholog of BLM, the Bloom’s syndrome gene, is a RecQ-related DNA helicase; cells from BLM patients are characterized by an increase in genome instability. Yeast strains bearing deletions in MEC1 or SGS1 are viable (in contrast to the inviability seen with loss of MEC1 in S. cerevisiae) but the different deletion mutants have significantly different phenotypes. The mec1Δ/Δ colonies have a wild-type colony morphology, while the sgs1Δ/Δ mutants are slow-growing, producing wrinkled colonies with pseudohyphal-like cells. The mec1Δ/Δ mutants are only sensitive to ethylmethane sulfonate (EMS), methylmethane sulfonate (MMS), and hydroxyurea (HU) but the sgs1Δ/Δ mutants exhibit a high sensitivity to all DNA-damaging agents tested. In an assay for chromosome 1 integrity, the mec1Δ/Δ mutants exhibit an increase in genome instability; no change was observed in the sgs1Δ/Δ mutants. Finally, loss of MEC1 does not affect sensitivity to the antifungal drug fluconazole, while loss of SGS1 leads to an increased susceptibility to fluconazole. Neither deletion elevated the level of antifungal drug resistance acquisition. PMID:21511048
Mutations associated with base excision repair deficiency and methylation-induced genotoxic stress
Sobol, Robert W.; Watson, David E.; Nakamura, Jun; Yakes, F. Michael; Hou, Esther; Horton, Julie K.; Ladapo, Joseph; Van Houten, Bennett; Swenberg, James A.; Tindall, Kenneth R.; Samson, Leona D.; Wilson, Samuel H.
2002-01-01
The long-term effect of exposure to DNA alkylating agents is entwined with the cell's genetic capacity for DNA repair and appropriate DNA damage responses. A unique combination of environmental exposure and deficiency in these responses can lead to genomic instability; this “gene–environment interaction” paradigm is a theme for research on chronic disease etiology. In the present study, we used mouse embryonic fibroblasts with a gene deletion in the base excision repair (BER) enzymes DNA β-polymerase (β-pol) and alkyladenine DNA glycosylase (AAG), along with exposure to methyl methanesulfonate (MMS) to study mutagenesis as a function of a particular gene–environment interaction. The β-pol null cells, defective in BER, exhibit a modest increase in spontaneous mutagenesis compared with wild-type cells. MMS exposure increases mutant frequency in β-pol null cells, but not in isogenic wild-type cells; UV light exposure or N-methyl-N′-nitro-N-nitrosoguanidine exposure increases mutant frequency similarly in both cell lines. The MMS-induced increase in mutant frequency in β-pol null cells appears to be caused by DNA lesions that are AAG substrates, because overexpression of AAG in β-pol null cells eliminates the effect. In contrast, β-pol/AAG double null cells are slightly more mutable than the β-pol null cells after MMS exposure. These results illustrate that BER plays a role in protecting mouse embryonic fibroblast cells against methylation-induced mutations and characterize the effect of a particular combination of BER gene defect and environmental exposure. PMID:11983862
Wit, Niek; Buoninfante, Olimpia Alessandra; van den Berk, Paul C M; Jansen, Jacob G; Hogenbirk, Marc A; de Wind, Niels; Jacobs, Heinz
2015-01-01
Translesion synthesis (TLS) provides a highly conserved mechanism that enables DNA synthesis on a damaged template. TLS is performed by specialized DNA polymerases of which polymerase (Pol) κ is important for the cellular response to DNA damage induced by benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), ultraviolet (UV) light and the alkylating agent methyl methanesulfonate (MMS). As TLS polymerases are intrinsically error-prone, tight regulation of their activity is required. One level of control is provided by ubiquitination of the homotrimeric DNA clamp PCNA at lysine residue 164 (PCNA-Ub). We here show that Polκ can function independently of PCNA modification and that Polη can function as a backup during TLS of MMS-induced lesions. Compared to cell lines deficient for PCNA modification (Pcna(K164R)) or Polκ, double mutant cell lines display hypersensitivity to MMS but not to BPDE or UV-C. Double mutant cells also displayed delayed post-replicative TLS, accumulate higher levels of replication stress and delayed S-phase progression. Furthermore, we show that Polη and Polκ are redundant in the DNA damage bypass of MMS-induced DNA damage. Taken together, we provide evidence for PCNA-Ub-independent activation of Polκ and establish Polη as an important backup polymerase in the absence of Polκ in response to MMS-induced DNA damage. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
A yeast-based genetic screening to identify human proteins that increase homologous recombination.
Collavoli, Anita; Comelli, Laura; Rainaldi, Giuseppe; Galli, Alvaro
2008-05-01
To identify new human proteins implicated in homologous recombination (HR), we set up 'a papillae assay' to screen a human cDNA library using the RS112 strain of Saccharomyces cerevisiae containing an intrachromosomal recombination substrate. We isolated 23 cDNAs, 11 coding for complete proteins and 12 for partially deleted proteins that increased HR when overexpressed in yeast. We characterized the effect induced by the overexpression of the complete human proteasome subunit beta 2, the partially deleted proteasome subunits alpha 3 and beta 8, the ribosomal protein L12, the brain abundant membrane signal protein (BASP1) and the human homologue to v-Ha-RAS (HRAS), which elevated HR by 2-6.5-fold over the control. We found that deletion of the RAD52 gene, which has a key role in most HR events, abolished the increase of HR induced by the proteasome subunits and HRAS; by contrast, the RAD52 deletion did not affect the high level of HR due to BASP1 and RPL12. This suggests that the proteins stimulated yeast HR via different mechanisms. Overexpression of the complete beta 2 human proteasome subunit or the partially deleted alpha 3 and beta 8 subunits increased methyl methanesulphonate (MMS) resistance much more in the rad52 Delta mutant than in the wild-type. Overexpression of RPL12 and BASP1 did not affect MMS resistance in both the wild-type and the rad52 Delta mutant, whereas HRAS decreased MMS resistance in the rad52 Delta mutant. The results indicate that these proteins may interfere with the pathway(s) involved in the repair of MMS-induced DNA damage. Finally, we provide further evidence that yeast is a helpful tool to identify human proteins that may have a regulatory role in HR.
Fujimuro, Masahiro; Nishiya, Tadashi; Nomura, Yasuyuki; Yokosawa, Hideyoshi
2005-12-01
Polyubiquitination plays key roles in various proteasome-dependent and independent cellular events. To elucidate roles in stress response of polyubiquitin chains formed via specific chain linkages in mammalian cells, we established NIH3T3 stable cell lines that are capable of conditionally expressing K29R, K48R and K63R ubiquitin mutants, in which the Lys29, Lys48 and Lys63 residues of ubiquitin had been changed to Arg, and we examined the effects of various stresses on their cell viabilities. The expression of K63R ubiquitin mutant decreased viability of the cells post-exposed to ethanol, H(2)O(2) and methyl methanesulfonate (MMS), while that of K48R mutant decreased viability of the cells post-exposed to heat shock as well as ethanol, H(2)O(2) and MMS. Thus, these results suggest that polyubiquitin chains formed via specific chain linkages are involved in the respective stress responses in mammalian cells.
Sensitivity of Magnetospheric Multi-Scale (MMS) Mission Navigation Accuracy to Major Error Sources
NASA Technical Reports Server (NTRS)
Olson, Corwin; Long, Anne; Car[emter. Russell
2011-01-01
The Magnetospheric Multiscale (MMS) mission consists of four satellites flying in formation in highly elliptical orbits about the Earth, with a primary objective of studying magnetic reconnection. The baseline navigation concept is independent estimation of each spacecraft state using GPS pseudorange measurements referenced to an Ultra Stable Oscillator (USO) with accelerometer measurements included during maneuvers. MMS state estimation is performed onboard each spacecraft using the Goddard Enhanced Onboard Navigation System (GEONS), which is embedded in the Navigator GPS receiver. This paper describes the sensitivity of MMS navigation performance to two major error sources: USO clock errors and thrust acceleration knowledge errors.
Sensitivity of Magnetospheric Multi-Scale (MMS) Mission Naviation Accuracy to Major Error Sources
NASA Technical Reports Server (NTRS)
Olson, Corwin; Long, Anne; Carpenter, J. Russell
2011-01-01
The Magnetospheric Multiscale (MMS) mission consists of four satellites flying in formation in highly elliptical orbits about the Earth, with a primary objective of studying magnetic reconnection. The baseline navigation concept is independent estimation of each spacecraft state using GPS pseudorange measurements referenced to an Ultra Stable Oscillator (USO) with accelerometer measurements included during maneuvers. MMS state estimation is performed onboard each spacecraft using the Goddard Enhanced Onboard Navigation System (GEONS), which is embedded in the Navigator GPS receiver. This paper describes the sensitivity of MMS navigation performance to two major error sources: USO clock errors and thrust acceleration knowledge errors.
Brown, Megan Sonntag; Lim, Elisha; Chen, Cheng; Nishant, K. T.; Alani, Eric
2013-01-01
Crossing over between homologous chromosomes occurs during the prophase of meiosis I and is critical for chromosome segregation. In baker’s yeast, two heterodimeric complexes, Msh4-Msh5 and Mlh1-Mlh3, act in meiosis to promote interference-dependent crossing over. Mlh1-Mlh3 also plays a role in DNA mismatch repair (MMR) by interacting with Msh2-Msh3 to repair insertion and deletion mutations. Mlh3 contains an ATP-binding domain that is highly conserved among MLH proteins. To explore roles for Mlh3 in meiosis and MMR, we performed a structure−function analysis of eight mlh3 ATPase mutants. In contrast to previous work, our data suggest that ATP hydrolysis by both Mlh1 and Mlh3 is important for both meiotic and MMR functions. In meiotic assays, these mutants showed a roughly linear relationship between spore viability and genetic map distance. To further understand the relationship between crossing over and meiotic viability, we analyzed crossing over on four chromosomes of varying lengths in mlh3Δ mms4Δ strains and observed strong decreases (6- to 17-fold) in crossing over in all intervals. Curiously, mlh3Δ mms4Δ double mutants displayed spore viability levels that were greater than observed in mms4Δ strains that show modest defects in crossing over. The viability in double mutants also appeared greater than would be expected for strains that show such severe defects in crossing over. Together, these observations provide insights for how Mlh1-Mlh3 acts in crossover resolution and MMR and for how chromosome segregation in Meiosis I can occur in the absence of crossing over. PMID:23316435
Jia, Qi; den Dulk-Ras, Amke; Shen, Hexi; Hooykaas, Paul J J; de Pater, Sylvia
2013-07-01
Besides the KU-dependent classical non-homologous end-joining (C-NHEJ) pathway, an alternative NHEJ pathway first identified in mammalian systems, which is often called the back-up NHEJ (B-NHEJ) pathway, was also found in plants. In mammalian systems PARP was found to be one of the essential components in B-NHEJ. Here we investigated whether PARP1 and PARP2 were also involved in B-NHEJ in Arabidopsis. To this end Arabidopsis parp1, parp2 and parp1parp2 (p1p2) mutants were isolated and functionally characterized. The p1p2 double mutant was crossed with the C-NHEJ ku80 mutant resulting in the parp1parp2ku80 (p1p2k80) triple mutant. As expected, because of their role in single strand break repair (SSBR) and base excision repair (BER), the p1p2 and p1p2k80 mutants were shown to be sensitive to treatment with the DNA damaging agent MMS. End-joining assays in cell-free leaf protein extracts of the different mutants using linear DNA substrates with different ends reflecting a variety of double strand breaks were performed. The results showed that compatible 5'-overhangs were accurately joined in all mutants, that KU80 protected the ends preventing the formation of large deletions and that PARP proteins were involved in microhomology mediated end joining (MMEJ), one of the characteristics of B-NHEJ.
Patenković, Aleksandra; Stamenković-Radak, Marina; Nikolić, Dragana; Marković, Tamara; Anđelković, Marko
2013-03-27
Gentiana lutea L., the yellow gentian, is herb known for its pharmacological properties, with a long tradition of use for the treatment of a variety of diseases including the use as a remedy for digestion, also in food products and in bitter beverages. The aim of the present study is to evaluate, for the first time, genotoxicity of gentian alone, and its antigenotoxicity against methyl methanesulfonate (MMS). The water infusion of the underground part of gentian were evaluated in vivo using the Drosophila wing spot test, at the dose commonly used in traditional medicine. For antigenotoxic study two types of treatment with gentian and MMS were performed: chronic co-treatment, as well as post-treatment with gentian after acute exposure with MMS. Water infusion of gentian alone did not exhibit genotoxicity. The results of co- and post-treatment experiments with gentian show that gentian enhanced the frequency of mutant clones over the values obtained with MMS alone, instead of reducing the genotoxicity of MMS, for 22.64% and 27.13% respectively. This result suggests a synergism of gentian with MMS, and indicates that water infusion of gentian used in traditional medicine may have particular effects with regard to genotoxicity indicating careful use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Shumilova, E; Shelud'ko, A V; Filip'echeva, Yu A; Evstigneeva, S S; Ponomareva, E G; Petrova, L P; Katsy, E I
2016-01-01
The previously obtained insertion mutants ofAzospirillum brasilense Sp245 in the genes mmsBl and fabG1 (strains SK039 and Sp245.1610, respectively) were characterized by impaired flagellation and motility. The putative products of expression of these genes are 3-hydroxyisobutyrate dehydrogenase and 3-oxoacyl-[acyl-carrier protein] reductase, respectively. In the present work, A. brasilense- Sp245 strains SK039 and Sp245.1610 were found to have differences in the content of 3-hydroxyhexadecanoic, hexadecanoic, 3-hydroxytetradecanoic, hexadecenoic, octadecenoic, and nonadecanoic acids in their lipopolysaccharide prepa- rations, as well as in cell hydrophobicity and hemagglutination activity and dynamics of cell aggregation, in biomass amount, and in the relative content of lipopolysaccharide antigens in mature biofilms formed on hydrophilic or hydrophobic surfaces.
Effect of surface hydrophobicity on the function of the immobilized biomineralization protein Mms6
Liu, Xunpei; Zhang, Honghu; Nayak, Srikanth; ...
2015-08-13
Magnetotactic bacteria produce magnetic nanocrystals with uniform shapes and sizes in nature, which has inspired in vitro synthesis of uniformly sized magnetite nanocrystals under mild conditions. Mms6, a biomineralization protein from magnetotactic bacteria with a hydrophobic N-terminal domain and a hydrophilic C-terminal domain, can promote formation of magnetite nanocrystals in vitro with well-defined shape and size in gels under mild conditions. Here we investigate the role of surface hydrophobicity on the ability of Mms6 to template magnetite nanoparticle formation on surfaces. Our results confirmed that Mms6 can form a protein network structure on a monolayer of hydrophobic octadecanethiol (ODT)-coated goldmore » surfaces and facilitate magnetite nanocrystal formation with uniform sizes close to those seen in nature, in contrast to its behavior on more hydrophilic surfaces. We propose that this hydrophobicity effect might be due to the amphiphilic nature of the Mms6 protein and its tendency to incorporate the hydrophobic N-terminal domain into the hydrophobic lipid bilayer environment of the magnetosome membrane, exposing the hydrophilic C-terminal domain that promotes biomineralization. Supporting this hypothesis, the larger and well-formed magnetite nanoparticles were found to be preferentially located on ODT surfaces covered with Mms6 as compared to control samples, as characterized by scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and atomic force microscopy studies. A C-terminal domain mutant of this protein did not form the same network structure as wild-type Mms6, suggesting that the network structure is important for the magnetite nanocrystal formation. This article provides valuable insights into the role of surface hydrophilicity on the action of the biomineralization protein Mms6 to synthesize magnetic nanocrystals and provides a facile route to controlling bioinspired nanocrystal synthesis in vitro.« less
Zhang, Jin-Liang; Wang, Hui-Yun; Yang, Qing; Lin, Shi-Yong; Luo, Guang-Yu; Zhang, Rong; Xu, Guo-Liang
2015-01-01
AIM: To investigate the clinical significance of methyl-methanesulfonate sensitivity 19 (MMS19) expression in esophageal squamous cell carcinoma (ESCC). METHODS: Between June 2008 and May 2013, specimens from 103 patients who underwent endoscopic biopsy for the diagnosis of ESCC at the endoscopy center of Sun Yat-Sen University Cancer Center were collected; 52 matched-normal esophageal squamous epithelium samples were biopsied as controls. MMS19 protein expression was measured by immunohistochemistry. Of the 103 cases of ESCC, 49 received radical surgery following neoadjuvant chemoradiotherapy consisting of concurrent radiation in a total dose of 40 Gy and two cycles of chemotherapy with vinorelbine and cisplatin. Relationships between MMS19 expression, clinicopathologic characteristics and chemoradiotherapy response were analyzed. RESULTS: The MMS19 protein could be detected in both the cytoplasm and nucleus of most specimens. High cytoplasmic expression of MMS19 was detected in 63.1% of ESCC samples, whereas high nuclear expression of MMS19 was found in 35.0%. High cytoplasmic MMS19 expression was associated with regional lymph node metastases (OR = 11.3, 95%CI: 2.3-54.7; P < 0.001) and distant metastases (OR = 13.1, 95%CI: 1.7-103.0; P = 0.002). Furthermore, high cytoplasmic MMS19 expression was associated with a response of ESCC to chemoradiotherapy (OR = 11.5, 95%CI: 3.0-44.5; P < 0.001), with a high cytoplasmic MMS19 expression rates in 79.3% and 25.0% of patients from the good chemoradiotherapy response group and poor response group, respectively. Nuclear MMS19 expression did not show any significant association with clinicopathologic characteristics or chemoradiotherapy response in ESCC. CONCLUSION: The results of our preliminary study suggest that MMS19 may be a potential new predictor of metastasis and chemoradiotherapy response in ESCC. PMID:25892874
Pandey, Kavita R; Joshi, Chetan; Vakil, Babu V
2016-01-01
Probiotics are microorganisms which when administered in adequate amounts confer health benefits to the host. A leading pharmaceutical company producing Bacillus coagulans as a probiotic was facing the problem of recurring phage attacks. Two mutants viz. B. co PIII and B. co MIII that were isolated as phage resistant mutants after UV irradiation and MMS treatment of phage sensitive B. coagulans parental culture were characterized at functional and molecular level and were noted to have undergone interesting genetic changes. The non-specific genetic alterations induced by mutagenesis can also lead to alterations in cell performance. Hence, in the current study the parental strain and the two mutants were selected for shake flask optimization. Plackett-Burman design was used to select the significant culture variables affecting biomass production. Evolutionary operation method was applied for further optimization. The study showed wide variations in the nutritional requirements of phage resistant mutants, post exposure to mutagens. An increment of 150, 134 and 152 % was observed in the biomass productions of B. coagulans (parental type) and mutants B.co PIII and B.co MIII respectively, compared to the yield from one-factor-at-a-time technique. Using Logistic and modified Leudeking-Piret equations, biomass accumulation and substrate utilization efficiency of the bioprocess were determined. The experimental data was in agreement with the results predicted by statistical analysis and modelling. The developed model may be useful for controlling the growth and substrate consumption kinetics in large scale fermentation using B. coagulans .
Zhang, Honghu; Liu, Xunpei; Feng, Shuren; ...
2015-02-10
In this study, magnetotactic bacteria that produce magnetic nanocrystals of uniform size and well-defined morphologies have inspired the use of biomineralization protein Mms6 to promote formation of uniform magnetic nanocrystals in vitro. Small angle X-ray scattering (SAXS) studies in physiological solutions reveal that Mms6 forms compact globular three-dimensional (3D) micelles (approximately 10 nm in diameter) that are, to a large extent, independent of concentration. In the presence of iron ions in the solutions, the general micellar morphology is preserved, however, with associations among micelles that are induced by iron ions. Compared with Mms6, the m2Mms6 mutant (with the sequence ofmore » hydroxyl/carboxyl containing residues in the C-terminal domain shuffled) exhibits subtle morphological changes in the presence of iron ions in solutions. The analysis of the SAXS data is consistent with a hierarchical core–corona micellar structure similar to that found in amphiphilic polymers. The addition of ferric and ferrous iron ions to the protein solution induces morphological changes in the micellar structure by transforming the 3D micelles into objects of reduced dimensionality of 2, with fractal-like characteristics (including Gaussian-chain-like) or, alternatively, platelet-like structures.« less
Zielinski, Ingar Marie; Steenbergen, Bert; Schmidt, Anna; Klingels, Katrijn; Simon Martinez, Cristina; de Water, Pascal; Hoare, Brian
2018-03-23
To introduce the Windmill-task, a new objective assessment tool to quantify the presence of mirror movements (MMs) in children with unilateral cerebral palsy (UCP), which are typically assessed with the observation-based Woods and Teuber scale (W&T). Prospective, observational, cohort pilot study. Children's hospital. Prospective cohort of children (N=23) with UCP (age range, 6-15y, mean age, 10.5±2.7y). Not applicable. The concurrent validity of the Windmill-task is assessed, and the sensitivity and specificity for MM detection are compared between both assessments. To assess the concurrent validity, Windmill-task data are compared with W&T data using Spearman rank correlations (ρ) for 2 conditions: affected hand moving vs less affected hand moving. Sensitivity and specificity are compared by measuring the mean percentage of children being assessed inconsistently across both assessments. Outcomes of both assessments correlated significantly (affected hand moving: ρ=.520; P=.005; less affected hand moving: ρ=.488; P=.009). However, many children displayed MMs on the Windmill-task, but not on the W&T (sensitivity: affected hand moving: 27.5%; less affected hand moving: 40.6%). Only 2 children displayed MMs on the W&T, but not on the Windmill-task (specificity: affected hand moving: 2.9%; less affected hand moving: 1.4%). The Windmill-task seems to be a valid tool to assess MMs in children with UCP and has an additional advantage of sensitivity to detect MMs. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Jelezcova, Elena; Trivedi, Ram N.; Wang, Xiao-hong; Tang, Jiang-bo; Brown, Ashley R.; Goellner, Eva M.; Schamus, Sandy; Fornsaglio, Jamie L.; Sobol, Robert W.
2010-01-01
Alkylating agents induce cell death in wild-type (WT) mouse embryonic fibroblasts (MEFs) by multiple mechanisms, including apoptosis, autophagy and necrosis. DNA polymerase β (Pol β) knockout (KO) MEFs are hypersensitive to the cytotoxic effect of alkylating agents, as compared to WT MEFs. To test the hypothesis that Parp1 is preferentially activated by methyl methanesulfonate (MMS) exposure of Pol β KO MEFs, we have examined the relationship between Pol β expression, Parp1 activation and cell survival following MMS exposure in a series of WT and Pol β deficient MEF cell lines. Consistent with our hypothesis, we observed elevated Parp1 activation in Pol β KO MEFs as compared to matched WT MEFs. Both the MMS-induced activation of Parp1 and the MMS-induced cytoxicity of Pol β KO MEFs are attenuated by pre-treatment with the Parp1/Parp2 inhibitor PJ34. Further, elevated Parp1 activation is observed following knockdown (KD) of endogenous Pol β, as compared to WT cells. Pol β KD MEFs are hypersensitive to MMS and both the MMS-induced hypersensitivity and Parp1 activation is prevented by pre-treatment with PJ34. In addition, the MMS-induced cellular sensitivity of Pol β KO MEFs is reversed when Parp1 is also deleted (Pol β/Parp1 double KO MEFs) and we observe no MMS sensitivity differential between Pol β/Parp1 double KO MEFs and those that express recombinant mouse Pol β. These studies suggest that Parp1 may function as a sensor of BER to initiate cell death when BER is aborted or fails. Parp1 may therefore function in BER as a tumor suppressor by initiating cell death and preventing the accumulation of cells with chromosomal damage due to a BER defect. PMID:20096707
Galli, Alvaro; Cervelli, Tiziana; Schiestl, Robert H
2003-05-01
The DNA polymerase delta (Pol3p/Cdc2p) allele pol3-t of Saccharomyces cerevisiae has previously been shown to increase the frequency of deletions between short repeats (several base pairs), between homologous DNA sequences separated by long inverted repeats, and between distant short repeats, increasing the frequency of genomic deletions. We found that the pol3-t mutation increased intrachromosomal recombination events between direct DNA repeats up to 36-fold and interchromosomal recombination 14-fold. The hyperrecombination phenotype of pol3-t was partially dependent on the Rad52p function but much more so on Rad1p. However, in the double-mutant rad1 Delta rad52 Delta, the pol3-t mutation still increased spontaneous intrachromosomal recombination frequencies, suggesting that a Rad1p Rad52p-independent single-strand annealing pathway is involved. UV and gamma-rays were less potent inducers of recombination in the pol3-t mutant, indicating that Pol3p is partly involved in DNA-damage-induced recombination. In contrast, while UV- and gamma-ray-induced intrachromosomal recombination was almost completely abolished in the rad52 or the rad1 rad52 mutant, there was still good induction in those mutants in the pol3-t background, indicating channeling of lesions into the above-mentioned Rad1p Rad52p-independent pathway. Finally, a heterozygous pol3-t/POL3 mutant also showed an increased frequency of deletions and MMS sensitivity at the restrictive temperature, indicating that even a heterozygous polymerase delta mutation might increase the frequency of genetic instability.
Cost-effectiveness analysis of a hospital electronic medication management system
Gospodarevskaya, Elena; Li, Ling; Richardson, Katrina L; Roffe, David; Heywood, Maureen; Day, Richard O; Graves, Nicholas
2015-01-01
Objective To conduct a cost–effectiveness analysis of a hospital electronic medication management system (eMMS). Methods We compared costs and benefits of paper-based prescribing with a commercial eMMS (CSC MedChart) on one cardiology ward in a major 326-bed teaching hospital, assuming a 15-year time horizon and a health system perspective. The eMMS implementation and operating costs were obtained from the study site. We used data on eMMS effectiveness in reducing potential adverse drug events (ADEs), and potential ADEs intercepted, based on review of 1 202 patient charts before (n = 801) and after (n = 401) eMMS. These were combined with published estimates of actual ADEs and their costs. Results The rate of potential ADEs following eMMS fell from 0.17 per admission to 0.05; a reduction of 71%. The annualized eMMS implementation, maintenance, and operating costs for the cardiology ward were A$61 741 (US$55 296). The estimated reduction in ADEs post eMMS was approximately 80 actual ADEs per year. The reduced costs associated with these ADEs were more than sufficient to offset the costs of the eMMS. Estimated savings resulting from eMMS implementation were A$63–66 (US$56–59) per admission (A$97 740–$102 000 per annum for this ward). Sensitivity analyses demonstrated results were robust when both eMMS effectiveness and costs of actual ADEs were varied substantially. Conclusion The eMMS within this setting was more effective and less expensive than paper-based prescribing. Comparison with the few previous full economic evaluations available suggests a marked improvement in the cost–effectiveness of eMMS, largely driven by increased effectiveness of contemporary eMMs in reducing medication errors. PMID:25670756
Cost-effectiveness analysis of a hospital electronic medication management system.
Westbrook, Johanna I; Gospodarevskaya, Elena; Li, Ling; Richardson, Katrina L; Roffe, David; Heywood, Maureen; Day, Richard O; Graves, Nicholas
2015-07-01
To conduct a cost-effectiveness analysis of a hospital electronic medication management system (eMMS). We compared costs and benefits of paper-based prescribing with a commercial eMMS (CSC MedChart) on one cardiology ward in a major 326-bed teaching hospital, assuming a 15-year time horizon and a health system perspective. The eMMS implementation and operating costs were obtained from the study site. We used data on eMMS effectiveness in reducing potential adverse drug events (ADEs), and potential ADEs intercepted, based on review of 1 202 patient charts before (n = 801) and after (n = 401) eMMS. These were combined with published estimates of actual ADEs and their costs. The rate of potential ADEs following eMMS fell from 0.17 per admission to 0.05; a reduction of 71%. The annualized eMMS implementation, maintenance, and operating costs for the cardiology ward were A$61 741 (US$55 296). The estimated reduction in ADEs post eMMS was approximately 80 actual ADEs per year. The reduced costs associated with these ADEs were more than sufficient to offset the costs of the eMMS. Estimated savings resulting from eMMS implementation were A$63-66 (US$56-59) per admission (A$97 740-$102 000 per annum for this ward). Sensitivity analyses demonstrated results were robust when both eMMS effectiveness and costs of actual ADEs were varied substantially. The eMMS within this setting was more effective and less expensive than paper-based prescribing. Comparison with the few previous full economic evaluations available suggests a marked improvement in the cost-effectiveness of eMMS, largely driven by increased effectiveness of contemporary eMMs in reducing medication errors. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.
Attitude Ground System (AGS) for the Magnetospheric Multi-Scale (MMS) Mission
NASA Technical Reports Server (NTRS)
Raymond, Juan C.; Sedlak, Joseph E.; Vint, Babak
2015-01-01
MMS Overview Recall from Conrads presentation earlier today MMS launch: March 13, 2015 on an Atlas V from Space Launch Complex 40, Cape Canaveral, Florida MMS Observatory Separation: five minute intervals spinning at 3 rpm approximately 1.5 hours after launch MMS Science Goals: study magnetospheric plasma physics and understand the processes that cause power grids, communication disruptions and Aurora formation Mission: 4 identical spacecraft in tetrahedral formation with variable size1.2 x 12 RE in Phase 1, with apogee on dayside to observe bow shock1.2 x 25 RE in Phase 2, with apogee on night side to observe magneto tail Challenges Tight attitude control box, orbit and formation maintenance requirements Maneuvers on thrusters every two weeks Delta-H Spin axis direction and spin rate maintenance Delta-V Orbit and Formation maintenance Mission phase transitions AGS support Smart targeting prediction of Spin-Axis attitude in the presence of environmental torques to stay within the science attitude Determination of the spacecraft attitude and spin rate (sensitive to knowledge of inertia tensor)Calibrations to improve attitude determination results and improve orbit maneuvers Mass properties (Center of Mass, and inertia tensor for nutation and coning) Accelerometer bias (sensitive to the accuracy of the rate estimates) Sensor alignments.
Yu, Chuan-Hang; Chen, Huang-Hsu; Liu, Chia-Ming; Jeng, Yung-Ming; Wang, Jeng-Tzung; Wang, Yi-Ping; Liu, Bu-Yuan; Sun, Andy; Chiang, Chun-Pin
2005-10-01
Primary mucosal melanomas (MMs) of the head and neck are a rare entity. Melanomas with characteristic melanin-pigmented tumor cells are easy to diagnose, but those without melanin-pigmented tumor cells, amelanotic melanomas, are difficult to identify and need immunohistochemistry (IHC) to confirm the final diagnosis. In this study, we examined the expression of three melanocytic differentiation markers, HMB-45, S-100, and Melan-A in primary oral and nasal MMs. We tried to evaluate whether HMB-45, S-100, and Melan-A were useful for diagnosis of primary oral and nasal MMs and to find out which marker was the best of the three. This study used IHC to examine the expression of HMB-45, S-100, and Melan-A in 17 formalin-fixed paraffin-embedded specimens of primary oral and nasal MMs. The staining intensities (SIs) and labeling indices (LIs) of HMB-45, S-100, and Melan-A in 17 MMs were calculated and compared between any two markers. Immunostaining results showed that the positive rate was 94% (16 of 17) for HMB-45, 88% (15 of 17) for S-100, and 71% (12 of 17) for Melan-A in 17 MMs. The SI of HMB-45 was significantly higher than that of S-100 (P = 0.0011) or of Melan-A (P = 0.0034). In addition, the mean LI of Melan-A (59 +/- 43%) was significantly lower than that of HMB-45 (83 +/- 28%, P = 0.0065) or of S-100 (79 +/- 33%, P = 0.0237). Our results indicate that both HMB-45 and S-100 show a high positive rate and LI in MMs and therefore may be good markers for immunohistochemical diagnosis of primary oral and nasal MMs. In addition, HMB-45 may be a more sensitive marker than S-100 because HMB-45 shows a significantly higher SI than S-100 in this study.
NASA Technical Reports Server (NTRS)
Winternitz, Luke B.; Bamford, William A.; Price, Samuel R.
2017-01-01
As reported in a companion work, in its first phase, NASA's 2015 highly elliptic Magnetospheric Multiscale (MMS) mission set a record for the highest altitude operational use of on-board GPS-based navigation, returning state estimates at 12 Earth radii. In early 2017 MMS transitioned to its second phase which doubled the apogee distance to 25 Earth radii, approaching halfway to the Moon. This paper will present results for GPS observability and navigation performance achieved in MMS Phase 2. Additionally, it will provide simulation results predicting the performance of the MMS navigation system applied to a pair of concept missions at Lunar distances. These studies will demonstrate how high-sensitivity GPS (or GNSS) receivers paired with onboard navigation software, as in MMS-Navigation system, can extend the envelope of autonomous onboard GPS navigation far from the Earth.
Study of Multimission Modular Spacecraft (MMS) propulsion requirements
NASA Technical Reports Server (NTRS)
Fischer, N. H.; Tischer, A. E.
1977-01-01
The cost effectiveness of various propulsion technologies for shuttle-launched multimission modular spacecraft (MMS) missions was determined with special attention to the potential role of ion propulsion. The primary criterion chosen for comparison for the different types of propulsion technologies was the total propulsion related cost, including the Shuttle charges, propulsion module costs, upper stage costs, and propulsion module development. In addition to the cost comparison, other criteria such as reliability, risk, and STS compatibility are examined. Topics covered include MMS mission models, propulsion technology definition, trajectory/performance analysis, cost assessment, program evaluation, sensitivity analysis, and conclusions and recommendations.
Knoll, Alexander; Higgins, James D; Seeliger, Katharina; Reha, Sarah J; Dangel, Natalie J; Bauknecht, Markus; Schröpfer, Susan; Franklin, F Christopher H; Puchta, Holger
2012-04-01
The human hereditary disease Fanconi anemia leads to severe symptoms, including developmental defects and breakdown of the hematopoietic system. It is caused by single mutations in the FANC genes, one of which encodes the DNA translocase FANCM (for Fanconi anemia complementation group M), which is required for the repair of DNA interstrand cross-links to ensure replication progression. We identified a homolog of FANCM in Arabidopsis thaliana that is not directly involved in the repair of DNA lesions but suppresses spontaneous somatic homologous recombination via a RecQ helicase (At-RECQ4A)-independent pathway. In addition, it is required for double-strand break-induced homologous recombination. The fertility of At-fancm mutant plants is compromised. Evidence suggests that during meiosis At-FANCM acts as antirecombinase to suppress ectopic recombination-dependent chromosome interactions, but this activity is antagonized by the ZMM pathway to enable the formation of interference-sensitive crossovers and chromosome synapsis. Surprisingly, mutation of At-FANCM overcomes the sterility phenotype of an At-MutS homolog4 mutant by apparently rescuing a proportion of crossover-designated recombination intermediates via a route that is likely At-MMS and UV sensitive81 dependent. However, this is insufficient to ensure the formation of an obligate crossover. Thus, At-FANCM is not only a safeguard for genome stability in somatic cells but is an important factor in the control of meiotic crossover formation.
Optimal Mutagen Doses for Emiliania huxleyi
NASA Astrophysics Data System (ADS)
Byrne, P.
2016-02-01
Emiliania huxleyi (E. huxleyi) is one of the most prominent coccolithophores. Given favorable conditions, E. huxleyi blooms can reach sizes exceeding 100,000km2, with densities of 107 cells per L (Olson & Strom 2002). With increasing demand and limited supply of fossil fuels, it has become increasingly popular to look toward alternative renewable fuel sources. E. Huxleyi store energy predominately as uniquely structured polyunsaturated long chain (C37-39) alkenes, alkenones and alkenoates (abbreviated as PULCAs) (Eltgroth et al 2005). Unlike the stored energy of macroalgae and higher order plants, triacylglycerols (TAGs), PULCAs provide a similar composition to native petroleum crude oils (Yamane 2013), which offers a more cost effective and higher yielding extraction process (Wu et al 1999). A number of factors have been shown to influence the alkenone content of E. huxleyi, such as nitrogen deficiency, phosphate limitation (Li et al 2014), and temperature (Shiraiwa et al 2005). For these reasons E. huxleyi has the potential to be an attractive system for algal biofuel. The broad and long-term objective of our research is to elucidate the alkenone biosynthesis pathway in E. Huxleyi, using random mutagenesis techniques. We propose to use UV light and methylmethane sulfonate (MMS) to create a mutant population, from which clones unable to synthesize alkenones will be selected. Identifying genes whose specific mutations underlie the loss-of-function phenotype will then reveal genes of interest. The aim of this research was to determine the UV and MMS dose response rates for E. huxleyi to ascertain optimal doses defined as a 50% survival rate for each of the two mutagens. Preliminary data indicate that E. huxleyi appear to be highly sensitive to UV mutagenesis, with an LD50 of 0.57mJ/cm2 for the calcifying strain M217 and 0.96mJ/cm2 for the non-calcifying strain CCMP1516. Both calcifying and non-calcifying strains exhibit similar LD50 values for MMS at 1-2% (v/v).
Nakata, Shiori; Watanabe, Tadashi; Nakagawa, Koji; Takeda, Hiroshi; Ito, Akihiro; Fujimuro, Masahiro
2016-03-25
Polyubiquitination plays key roles in proteasome-dependent and independent cellular events, whereas monoubiquitination is involved in gene expression, DNA repair, protein-protein interaction, and protein trafficking. We previously developed an FK2 antibody, which specifically recognizes poly-Ub moieties but not free Ub. To elucidate the role of Ub conjugation in response to cellular stress, we used FK2 to investigate whether chemical stress (rapamycin, ethanol, or hydroxyurea), ER stress (thapsigargin or tunicamycin), heat shock or DNA damage (H2O2 or methyl methanesulfonate) affect the formation of Ub conjugates including histone H2A (hH2A) ubiquitination. First, we found that all forms of stress tested increased poly-ubiquitinated proteins in HeLa cells. Furthermore, rapamycin and hydroxyurea treatment, and ER stress increased ubiquitination of hH2A, while methyl methanesulfonate (MMS) treatment induced deubiquitination of hH2A. The ethanol and H2O2 treatments, and heat shock transiently induced hH2A de-ubiquitination, although deubiquitinated hH2A were ubiquitinated again by subsequent cultivation. We also revealed that FK2 reacts with not only polyubiquitinated proteins but also mono-ubiquitinated hH2A. With the exception of MMS, all forms of stress tested increased the acetylation of K5-hH2A, K9-hH3 and K8-hH4 in addition to ubiquitination. K118 and K119 of hH2A were ubiquitinated in cells under normal conditions, and K119 was the major ubiquitination site. The MMS-treatment and heat shock induced the deubiquitination of both K118 and K119-histone H2A. Interestingly, MMS treatment did not affect cell HeLa cell viability expressing double-mutant hH2A (KK118,119AA-hH2A), while heat shock slightly but significantly decreased viability of double-mutant hH2A expressing cells, indicating that ubiquitination of both sites associates with recovery from heat shock but not MMS treatment. Thus, we characterized FK2 reactivity and demonstrated that various stresses alter the ubiquitination status, particularly ubiquitinated hH2A and with histone acetylation, and highlight the physiological importance of hH2A ubiquitination after exposure to stress stimuli. Copyright © 2016 Elsevier Inc. All rights reserved.
Kitanovic, Ana; Walther, Thomas; Loret, Marie Odile; Holzwarth, Jinda; Kitanovic, Igor; Bonowski, Felix; Van Bui, Ngoc; Francois, Jean Marie; Wölfl, Stefan
2009-06-01
Maintenance and adaptation of energy metabolism could play an important role in the cellular ability to respond to DNA damage. A large number of studies suggest that the sensitivity of cells to oxidants and oxidative stress depends on the activity of cellular metabolism and is dependent on the glucose concentration. In fact, yeast cells that utilize fermentative carbon sources and hence rely mainly on glycolysis for energy appear to be more sensitive to oxidative stress. Here we show that treatment of the yeast Saccharomyces cerevisiae growing on a glucose-rich medium with the DNA alkylating agent methyl methanesulphonate (MMS) triggers a rapid inhibition of respiration and enhances reactive oxygen species (ROS) production, which is accompanied by a strong suppression of glycolysis. Further, diminished activity of pyruvate kinase and glyceraldehyde-3-phosphate dehydrogenase upon MMS treatment leads to a diversion of glucose carbon to glycerol, trehalose and glycogen accumulation and an increased flux through the pentose-phosphate pathway. Such conditions finally result in a significant decline in the ATP level and energy charge. These effects are dependent on the glucose concentration in the medium. Our results clearly demonstrate that calorie restriction reduces MMS toxicity through increased respiration and reduced ROS accumulation, enhancing the survival and recovery of cells.
The meteorological monitoring system for the Kennedy Space Center/Cape Canaveral Air Station
NASA Technical Reports Server (NTRS)
Dianic, Allan V.
1994-01-01
The Kennedy Space Center (KSC) and Cape Canaveral Air Station (CCAS) are involved in many weather-sensitive operations. Manned and unmanned vehicle launches, which occur several times each year, are obvious example of operations whose success and safety are dependent upon favorable meteorological conditions. Other operations involving NASA, Air Force, and contractor personnel, including daily operations to maintain facilities, refurbish launch structures, prepare vehicles for launch, and handle hazardous materials, are less publicized but are no less weather-sensitive. The Meteorological Monitoring System (MMS) is a computer network which acquires, processes, disseminates, and monitors near real-time and forecast meteorological information to assist operational personnel and weather forecasters with the task of minimizing the risk to personnel, materials, and the surrounding population. CLIPS has been integrated into the MMS to provide quality control analysis and data monitoring. This paper describes aspects of the MMS relevant to CLIPS including requirements, actual implementation details, and results of performance testing.
Optimized merging of search coil and fluxgate data for MMS
NASA Astrophysics Data System (ADS)
Fischer, David; Magnes, Werner; Hagen, Christian; Dors, Ivan; Chutter, Mark W.; Needell, Jerry; Torbert, Roy B.; Le Contel, Olivier; Strangeway, Robert J.; Kubin, Gernot; Valavanoglou, Aris; Plaschke, Ferdinand; Nakamura, Rumi; Mirioni, Laurent; Russell, Christopher T.; Leinweber, Hannes K.; Bromund, Kenneth R.; Le, Guan; Kepko, Lawrence; Anderson, Brian J.; Slavin, James A.; Baumjohann, Wolfgang
2016-11-01
The Magnetospheric Multiscale mission (MMS) targets the characterization of fine-scale current structures in the Earth's tail and magnetopause. The high speed of these structures, when traversing one of the MMS spacecraft, creates magnetic field signatures that cross the sensitive frequency bands of both search coil and fluxgate magnetometers. Higher data quality for analysis of these events can be achieved by combining data from both instrument types and using the frequency bands with best sensitivity and signal-to-noise ratio from both sensors. This can be achieved by a model-based frequency compensation approach which requires the precise knowledge of instrument gain and phase properties. We discuss relevant aspects of the instrument design and the ground calibration activities, describe the model development and explain the application on in-flight data. Finally, we show the precision of this method by comparison of in-flight data. It confirms unity gain and a time difference of less than 100 µs between the different magnetometer instruments.
H4K20me0 marks post-replicative chromatin and recruits the TONSL₋MMS22L DNA repair complex
DOE Office of Scientific and Technical Information (OSTI.GOV)
Saredi, Giulia; Huang, Hongda; Hammond, Colin M.
Here, we report that after DNA replication, chromosomal processes including DNA repair and transcription take place in the context of sister chromatids. While cell cycle regulation can guide these processes globally, mechanisms to distinguish pre- and post-replicative states locally remain unknown. In this paper we reveal that new histones incorporated during DNA replication provide a signature of post-replicative chromatin, read by the human TONSL–MMS22L 1, 2, 3, 4 homologous recombination complex. We identify the TONSL ankyrin repeat domain (ARD) as a reader of histone H4 tails unmethylated at K20 (H4K20me0), which are specific to new histones incorporated during DNA replicationmore » and mark post-replicative chromatin until the G2/M phase of the cell cycle. Accordingly, TONSL–MMS22L binds new histones H3–H4 both before and after incorporation into nucleosomes, remaining on replicated chromatin until late G2/M. H4K20me0 recognition is required for TONSL–MMS22L binding to chromatin and accumulation at challenged replication forks and DNA lesions. Consequently, TONSL ARD mutants are toxic, compromising genome stability, cell viability and resistance to replication stress. Finally, together, these data reveal a histone-reader-based mechanism for recognizing the post-replicative state, offering a new angle to understand DNA repair with the potential for targeted cancer therapy.« less
Genotoxic damage in polychaetes: a study of species and cell-type sensitivities.
Lewis, Ceri; Galloway, Tamara
2008-06-30
The marine environment is becoming increasingly contaminated by environmental pollutants with the potential to damage DNA, with marine sediments acting as a sink for many of these contaminants. Understanding genotoxic responses in sediment-dwelling marine organisms, such as polychaetes, is therefore of increasing importance. This study is an exploration of species-specific and cell-specific differences in cell sensitivities to DNA-damaging agents in polychaete worms, aimed at increasing fundamental knowledge of their responses to genotoxic damage. The sensitivities of coelomocytes from three polychaetes species of high ecological relevance, i.e. the lugworm Arenicola marina, the harbour ragworm Nereis diversicolor and the king ragworm Nereis virens to genotoxic damage are compared, and differences in sensitivities of their different coelomic cell types determined by use of the comet assay. A. marina was found to be the most sensitive to genotoxic damage induced by the direct-acting mutagen methyl methanesulfonate (MMS), and showed dose-dependent responses to MMS and the polycyclic aromatic hydrocarbon benzo(a)pyrene. Significant differences in sensitivity were also measured for the different types of coelomocyte. Eleocytes were more sensitive to induction of DNA damage than amoebocytes in both N. virens and N. diversicolor. Spermatozoa from A. marina showed significant DNA damage following in vitro exposure to MMS, but were less sensitive to DNA damage than coelomocytes. This investigation has clearly demonstrated that different cell types within the same species and different species within the polychaetes show significantly different responses to genotoxic insult. These findings are discussed in terms of the relationship between cell function and sensitivity and their implications for the use of polychaetes in environmental genotoxicity studies.
A multimodal spectroscopy system for real-time disease diagnosis
NASA Astrophysics Data System (ADS)
Šćepanović, Obrad R.; Volynskaya, Zoya; Kong, Chae-Ryon; Galindo, Luis H.; Dasari, Ramachandra R.; Feld, Michael S.
2009-04-01
The combination of reflectance, fluorescence, and Raman spectroscopy—termed multimodal spectroscopy (MMS)—provides complementary and depth-sensitive information about tissue composition. As such, MMS is a promising tool for disease diagnosis, particularly in atherosclerosis and breast cancer. We have developed an integrated MMS instrument and optical fiber spectral probe for simultaneous collection of all three modalities in a clinical setting. The MMS instrument multiplexes three excitation sources, a xenon flash lamp (370-740 nm), a nitrogen laser (337 nm), and a diode laser (830 nm), through the MMS probe to excite tissue and collect the spectra. The spectra are recorded on two spectrograph/charge-coupled device modules, one optimized for visible wavelengths (reflectance and fluorescence) and the other for the near-infrared (Raman), and processed to provide diagnostic parameters. We also describe the design and calibration of a unitary MMS optical fiber probe 2 mm in outer diameter, containing a single appropriately filtered excitation fiber and a ring of 15 collection fibers, with separate groups of appropriately filtered fibers for efficiently collecting reflectance, fluorescence, and Raman spectra from the same tissue location. A probe with this excitation/collection geometry has not been used previously to collect reflectance and fluorescence spectra, and thus physical tissue models ("phantoms") are used to characterize the probe's spectroscopic response. This calibration provides probe-specific modeling parameters that enable accurate extraction of spectral parameters. This clinical MMS system has been used recently to analyze artery and breast tissue in vivo and ex vivo.
The Modular Modeling System (MMS): A toolbox for water- and environmental-resources management
Leavesley, G.H.; Markstrom, S.L.; Viger, R.J.; Hay, L.E.; ,
2005-01-01
The increasing complexity of water- and environmental-resource problems require modeling approaches that incorporate knowledge from a broad range of scientific and software disciplines. To address this need, the U.S. Geological Survey (USGS) has developed the Modular Modeling System (MMS). MMS is an integrated system of computer software for model development, integration, and application. Its modular design allows a high level of flexibility and adaptability to enable modelers to incorporate their own software into a rich array of built-in models and modeling tools. These include individual process models, tightly coupled models, loosely coupled models, and fully- integrated decision support systems. A geographic information system (GIS) interface, the USGS GIS Weasel, has been integrated with MMS to enable spatial delineation and characterization of basin and ecosystem features, and to provide objective parameter-estimation methods for models using available digital data. MMS provides optimization and sensitivity-analysis tools to analyze model parameters and evaluate the extent to which uncertainty in model parameters affects uncertainty in simulation results. MMS has been coupled with the Bureau of Reclamation object-oriented reservoir and river-system modeling framework, RiverWare, to develop models to evaluate and apply optimal resource-allocation and management strategies to complex, operational decisions on multipurpose reservoir systems and watersheds. This decision support system approach has been developed, tested, and implemented in the Gunnison, Yakima, San Joaquin, Rio Grande, and Truckee River basins of the western United States. MMS is currently being coupled with the U.S. Forest Service model SIMulating Patterns and Processes at Landscape Scales (SIMPPLLE) to assess the effects of alternative vegetation-management strategies on a variety of hydrological and ecological responses. Initial development and testing of the MMS-SIMPPLLE integration is being conducted on the Colorado Plateau region of the western United Sates.
Li, Xiao; Zhuo, Ran; Tiong, Stanley; Di Cara, Francesca; King-Jones, Kirst; Hughes, Sarah C.; Campbell, Shelagh D.; Wevrick, Rachel
2013-01-01
The SMC5/6 protein complex consists of the Smc5, Smc6 and Non-Smc-Element (Nse) proteins and is important for genome stability in many species. To identify novel components in the DNA repair pathway, we carried out a genetic screen to identify mutations that confer reduced resistance to the genotoxic effects of caffeine, which inhibits the ATM and ATR DNA damage response proteins. This approach identified inactivating mutations in CG5524 and MAGE, homologs of genes encoding Smc6 and Nse3 in yeasts. The fact that Smc5 mutants are also caffeine-sensitive and that Mage physically interacts with Drosophila homologs of Nse proteins suggests that the structure of the Smc5/6 complex is conserved in Drosophila. Although Smc5/6 proteins are required for viability in S. cerevisiae, they are not essential under normal circumstances in Drosophila. However, flies carrying mutations in Smc5, Smc6 and MAGE are hypersensitive to genotoxic agents such as ionizing radiation, camptothecin, hydroxyurea and MMS, consistent with the Smc5/6 complex serving a conserved role in genome stability. We also show that mutant flies are not compromised for pre-mitotic cell cycle checkpoint responses. Rather, caffeine-induced apoptosis in these mutants is exacerbated by inhibition of ATM or ATR checkpoint kinases but suppressed by Rad51 depletion, suggesting a functional interaction involving homologous DNA repair pathways that deserves further scrutiny. Our insights into the SMC5/6 complex provide new challenges for understanding the role of this enigmatic chromatin factor in multi-cellular organisms. PMID:23555814
KIT mutations in Russian patients with mucosal melanoma.
Abysheva, Svetlana N; Iyevleva, Aglaya G; Efimova, Nina V; Mokhina, Yulia B; Sabirova, Feruza A; Ivantsov, Alexandr O; Artemieva, Anna S; Togo, Alexandr V; Moiseyenko, Vladimir M; Matsko, Dmitry E; Imyanitov, Evgeny N
2011-12-01
A single institution series of 48 mucosal melanomas (MMs) has been analyzed for the presence of KIT mutations using high-resolution melting and sequencing of abnormally melted DNA fragments. The analysis of exons 9, 11, 13, and 17 has revealed eight of 48 (17%) nonsynonymous alterations, including zero of seven head and neck, six of 24 anorectal, one of 15 genitourinary, one of one gastric, and zero of one mediastinal MMs. Seven of these mutations were potentially associated with the tumor sensitivity to KIT tyrosine kinase inhibitors. One tumor harbored somatically acquired silent nucleotide substitution c.1383A>G (T461T). This study adds to the evidence that a substantial portion of MMs carry a therapeutically relevant mutation in the KIT oncogene.
Parke, Courtney; Tatum, Danielle; Lustig, Arthur J.
2014-01-01
The function of the replication clamp loaders in the semi-conservative telomere replication and their relationship to telomerase- and recombination mechanisms of telomere addition remains ambiguous. We have investigated the variant clamp loader Ctf18 RFC (Replication Factor C). To understand the role of Ctf18 at the telomere, we first investigated genetic interactions after loss of Ctf18 and TLC1 (the yeast telomerase RNA). We find that the tlc1▵ ctf18▵ double mutant confers a rapid >1000-fold decrease in viability. The rate of loss was similar to the kinetics of cell death in rad52▵ tlc1▵ cells. However, the Ctf18 pathway is distinct from Rad52, required for the repair of DSBs, as demonstrated by the synthetic lethality of rad52▵ tlc1▵ ctf18▵ triple mutants. These data suggest that each mutant elicits non-redundant defects acting on the same substrate. Second, interactions of the yeast hyper-recombinational mutant, mre11A470T, with ctf18▵ confer a synergistic cold sensitivity. The phenotype of these double mutants ultimately results in telomere loss and the generation of recombinational survivors. We observed a similar synergism between single mutants that led to hypersensitivity to the DNA alkylating agent, methane methyl sulphonate (MMS), the replication fork inhibitor hydroxyurea (HU), and to a failure to separate telomeres of sister chromatids. Hence, ctf18▵ and mre11A470T act in different pathways on telomere substrates for multiple phenotypes. The mre11A470T cells also displayed a DNA damage response (DDR) at 15°C but not at 30°C while ctf18▵ mutants conferred a constitutive DDR activity. Both the 15°C DDR pattern and growth rate were reversible at 30°C and displayed telomerase activity in vivo. We hypothesize that Ctf18 confers protection against stalling and/or breaks at the replication fork in cells that either lack, or are compromised for, telomerase activity. This Ctf18-based function is likely to contribute another level to telomere size homeostasis. PMID:24533124
Huang, Shuran; Gao, Lingyun; Chen, Yueqin; Guo, Xiang; Liu, Deguo; Wang, Jiehuan; Shi, Zhitao; Sun, Zhanguo; Jin, Feng; Chen, Weijian; Yang, Yunjun
2018-01-27
Vascular and hemodynamic changes were not consistent in symptomatic and non-symptomatic cerebral hemisphere in patients with symptomatic moyamoya syndrome (MMS). Thus, the purpose of this study is to evaluate the hemodynamic difference between symptomatic and non-symptomatic cerebral hemisphere in patients with symptomatic MMS. Patients who were diagnosed with symptomatic MMS were retrospectively collected. All cases underwent CTP examination. Regions of interest (ROIs) were chosen in the mirroring bilateral frontal lobes, temporal lobes, the basal ganglia, and the brainstem as control region. The relative perfusion parameter values of symptomatic side were compared with non-symptomatic side. Of the 40 patients, 33 patients were taken into assessment. In all cases (n = 33), rCBF, rMTT, and rTTP in all regions of interest (ROIs) of the symptomatic side were significantly different from those of contralateral side. In unilateral MMS patients (n = 7), rCBF values were not significantly different between two sides in the temporal lobe and basal ganglia area; rTTP values were significantly higher in the symptomatic side. rMTT values were significantly higher only in the temporal lobe of symptomatic side. In bilateral MMS patients (n = 26), rCBF and rMTT in all ROIs of the symptomatic side were significantly different from those of contralateral side. However, there were no significant differences between two sides in all ROIs on rTTP values. This study demonstrates that rCBF and rMTT were more sensitive than rTTP for evaluating hemodynamic changes in patients with symptomatic bilateral MMS. Furthermore, patients with unilateral MMS may have a preserved rCBF compared to those with bilateral disease.
Consultation of orthopaedics cases using multimedia messaging services.
Eranki, Vivek; Munt, Justin; Lim, Ming J; Atkinson, Robert
2010-04-23
Frequently, radiological data is transferred verbally between the Emergency Department (ED) and orthopaedic registrar. Given the different language skills and medical experience of health staff, there is often a limit to the adequacy of the verbal description that could lead to suboptimal patient care. This study proposes that concurrent review of MMS teleradiology with traditional verbal reporting results in a significant therapeutic benefit. Case notes of 40 patients who presented to ED were reviewed. Images were captured and sent to an Orthopaedic registrar along with a brief clinical synopsis. Information was collected on the diagnosis of the MMS radiograph, need for urgent admission and management plan outlined to ED. Correct diagnosis was made in 27 of 40 cases. Using the latest technology available, MMS teleradiology had 79% sensitivity, 83% specificity and an accuracy of 80%. 50% of paediatric fractures and 60% of undisplaced fractures were diagnosed successfully. MMS teleradiology is not suitable by itself as a remote diagnostic tool. However, when combined with existing clinical practice, it is effective in screening patients, enhances confidence in decision making and communication between doctors.
Gándara, Carolina; Alonso, Juan C
2015-03-01
Bacillus subtilis contains two vegetative diadenylate cyclases, DisA and CdaA, which produce cyclic di-AMP (c-di-AMP), and one phosphodiesterase, GdpP, that degrades it into a linear di-AMP. We report here that DisA and CdaA contribute to elicit repair of DNA damage generated by alkyl groups and H2O2, respectively, during vegetative growth. disA forms an operon with radA (also termed sms) that encodes a protein distantly related to RecA. Among different DNA damage agents tested, only methyl methane sulfonate (MMS) affected disA null strain viability, while radA showed sensitivity to all of them. A strain lacking both disA and radA was as sensitive to MMS as the most sensitive single parent (epistasis). Low c-di-AMP levels (e.g. by over-expressing GdpP) decreased the ability of cells to repair DNA damage caused by MMS and in less extent by H2O2, while high levels of c-di-AMP (absence of GdpP or expression of sporulation-specific diadenylate cyclase, CdaS) increased cell survival. Taken together, our results support the idea that c-di-AMP is a crucial signalling molecule involved in DNA repair with DisA and CdaA contributing to modulate different DNA damage responses during exponential growth. Copyright © 2015 Elsevier B.V. All rights reserved.
Development of Raman microspectroscopy for automated detection and imaging of basal cell carcinoma
NASA Astrophysics Data System (ADS)
Larraona-Puy, Marta; Ghita, Adrian; Zoladek, Alina; Perkins, William; Varma, Sandeep; Leach, Iain H.; Koloydenko, Alexey A.; Williams, Hywel; Notingher, Ioan
2009-09-01
We investigate the potential of Raman microspectroscopy (RMS) for automated evaluation of excised skin tissue during Mohs micrographic surgery (MMS). The main aim is to develop an automated method for imaging and diagnosis of basal cell carcinoma (BCC) regions. Selected Raman bands responsible for the largest spectral differences between BCC and normal skin regions and linear discriminant analysis (LDA) are used to build a multivariate supervised classification model. The model is based on 329 Raman spectra measured on skin tissue obtained from 20 patients. BCC is discriminated from healthy tissue with 90+/-9% sensitivity and 85+/-9% specificity in a 70% to 30% split cross-validation algorithm. This multivariate model is then applied on tissue sections from new patients to image tumor regions. The RMS images show excellent correlation with the gold standard of histopathology sections, BCC being detected in all positive sections. We demonstrate the potential of RMS as an automated objective method for tumor evaluation during MMS. The replacement of current histopathology during MMS by a ``generalization'' of the proposed technique may improve the feasibility and efficacy of MMS, leading to a wider use according to clinical need.
Inducible DNA-repair systems in yeast: competition for lesions.
Mitchel, R E; Morrison, D P
1987-03-01
DNA lesions may be recognized and repaired by more than one DNA-repair process. If two repair systems with different error frequencies have overlapping lesion specificity and one or both is inducible, the resulting variable competition for the lesions can change the biological consequences of these lesions. This concept was demonstrated by observing mutation in yeast cells (Saccharomyces cerevisiae) exposed to combinations of mutagens under conditions which influenced the induction of error-free recombinational repair or error-prone repair. Total mutation frequency was reduced in a manner proportional to the dose of 60Co-gamma- or 254 nm UV radiation delivered prior to or subsequent to an MNNG exposure. Suppression was greater per unit radiation dose in cells gamma-irradiated in O2 as compared to N2. A rad3 (excision-repair) mutant gave results similar to wild-type but mutation in a rad52 (rec-) mutant exposed to MNNG was not suppressed by radiation. Protein-synthesis inhibition with heat shock or cycloheximide indicated that it was the mutation due to MNNG and not that due to radiation which had changed. These results indicate that MNNG lesions are recognized by both the recombinational repair system and the inducible error-prone system, but that gamma-radiation induction of error-free recombinational repair resulted in increased competition for the lesions, thereby reducing mutation. Similarly, gamma-radiation exposure resulted in a radiation dose-dependent reduction in mutation due to MNU, EMS, ENU and 8-MOP + UVA, but no reduction in mutation due to MMS. These results suggest that the number of mutational MMS lesions recognizable by the recombinational repair system must be very small relative to those produced by the other agents. MNNG induction of the inducible error-prone systems however, did not alter mutation frequencies due to ENU or MMS exposure but, in contrast to radiation, increased the mutagenic effectiveness of EMS. These experiments demonstrate that in this lower eukaryote, mutagen exposure does not necessarily result in a fixed risk of mutation, but that the risk can be markedly influenced by a variety of external stimuli including heat shock or exposure to other mutagens.
Identification of Proteus mirabilis Mutants with Increased Sensitivity to Antimicrobial Peptides
McCoy, Andrea J.; Liu, Hongjian; Falla, Timothy J.; Gunn, John S.
2001-01-01
Antimicrobial peptides (APs) are important components of the innate defenses of animals, plants, and microorganisms. However, some bacterial pathogens are resistant to the action of APs. For example, Proteus mirabilis is highly resistant to the action of APs, such as polymyxin B (PM), protegrin, and the synthetic protegrin analog IB-367. To better understand this resistance, a transposon mutagenesis approach was used to generate P. mirabilis mutants sensitive to APs. Four unique PM-sensitive mutants of P. mirabilis were identified (these mutants were >2 to >128 times more sensitive than the wild type). Two of these mutants were also sensitive to IB-367 (16 and 128 times more sensitive than the wild type). Lipopolysaccharide (LPS) profiles of the PM- and protegrin-sensitive mutants demonstrated marked differences in both the lipid A and O-antigen regions, while the PM-sensitive mutants appeared to have alterations of either lipid A or O antigen. Matrix-assisted laser desorption ionization–time of flight mass spectrometry analysis of the wild-type and PM-sensitive mutant lipid A showed species with one or two aminoarabinose groups, while lipid A from the PM- and protegrin-sensitive mutants was devoid of aminoarabinose. When the mutants were streaked on an agar-containing medium, the swarming motility of the PM- and protegrin-sensitive mutants was completely inhibited and the swarming motility of the mutants sensitive to only PM was markedly decreased. DNA sequence analysis of the mutagenized loci revealed similarities to an O-acetyltransferase (PM and protegrin sensitive) and ATP synthase and sap loci (PM sensitive). These data further support the role of LPS modifications as an elaborate mechanism in the resistance of certain bacterial species to APs and suggest that LPS surface charge alterations may play a role in P. mirabilis swarming motility. PMID:11408219
NASA Technical Reports Server (NTRS)
Estes, Lyndon D.; Beukes, Hein; Bradley, Bethany A.; Debats, Stephanie R.; Oppenheimer, Michael; Ruane, Alex C.; Schulze, Roland; Tadross, Mark
2013-01-01
Crop model-specific biases are a key uncertainty affecting our understanding of climate change impacts to agriculture. There is increasing research focus on intermodel variation, but comparisons between mechanistic (MMs) and empirical models (EMs) are rare despite both being used widely in this field. We combined MMs and EMs to project future (2055) changes in the potential distribution (suitability) and productivity of maize and spring wheat in South Africa under 18 downscaled climate scenarios (9 models run under 2 emissions scenarios). EMs projected larger yield losses or smaller gains than MMs. The EMs' median-projected maize and wheat yield changes were 3.6% and 6.2%, respectively, compared to 6.5% and 15.2% for the MM. The EM projected a 10% reduction in the potential maize growing area, where the MM projected a 9% gain. Both models showed increases in the potential spring wheat production region (EM = 48%, MM = 20%), but these results were more equivocal because both models (particularly the EM) substantially overestimated the extent of current suitability. The substantial water-use efficiency gains simulated by the MMs under elevated CO2 accounted for much of the EMMM difference, but EMs may have more accurately represented crop temperature sensitivities. Our results align with earlier studies showing that EMs may show larger climate change losses than MMs. Crop forecasting efforts should expand to include EMMM comparisons to provide a fuller picture of crop-climate response uncertainties.
Che, Jun; Smith, Stephanie; Kim, Yoo Jung; Shim, Eun Yong; Myung, Kyungjae; Lee, Sang Eun
2015-01-01
Break-induced replication (BIR) has been implicated in restoring eroded telomeres and collapsed replication forks via single-ended invasion and extensive DNA synthesis on the recipient chromosome. Unlike other recombination subtypes, DNA synthesis in BIR likely relies heavily on mechanisms enabling efficient fork progression such as chromatin modification. Herein we report that deletion of HST3 and HST4, two redundant de-acetylases of histone H3 Lysine 56 (H3K56), inhibits BIR, sensitizes checkpoint deficient cells to deoxyribonucleotide triphosphate pool depletion, and elevates translocation-type gross chromosomal rearrangements (GCR). The basis for deficiency in BIR and gene conversion with long gap synthesis in hst3Δ hst4Δ cells can be traced to a defect in extensive DNA synthesis. Distinct from other cellular defects associated with deletion of HST3 and HST4 including thermo-sensitivity and elevated spontaneous mutagenesis, the BIR defect in hst3Δ hst4Δ cannot be offset by the deletion of RAD17 or MMS22, but rather by the loss of RTT109 or ASF1, or in combination with the H3K56R mutation, which also restores tolerance to replication stress in mrc1 mutants. Our studies suggest that acetylation of H3K56 limits extensive repair synthesis and interferes with efficient fork progression in BIR. PMID:25705897
Functional conservation of the yeast and Arabidopsis RAD54-like genes.
Klutstein, Michael; Shaked, Hezi; Sherman, Amir; Avivi-Ragolsky, Naomi; Shema, Efrat; Zenvirth, Drora; Levy, Avraham A; Simchen, Giora
2008-04-01
The Saccharomyces cerevisiae RAD54 gene has critical roles in DNA double-strand break repair, homologous recombination, and gene targeting. Previous results show that the yeast gene enhances gene targeting when expressed in Arabidopsis thaliana. In this work we address the trans-species compatibility of Rad54 functions. We show that overexpression of yeast RAD54 in Arabidopsis enhances DNA damage resistance severalfold. Thus, the yeast gene is active in the Arabidopsis homologous-recombination repair system. Moreover, we have identified an A. thaliana ortholog of yeast RAD54, named AtRAD54. This gene, with close sequence similarity to RAD54, complements methylmethane sulfonate (MMS) sensitivity but not UV sensitivity or gene targeting defects of rad54Delta mutant yeast cells. Overexpression of AtRAD54 in Arabidopsis leads to enhanced resistance to DNA damage. This gene's assignment as a RAD54 ortholog is further supported by the interaction of AtRad54 with AtRad51 and the interactions between alien proteins (i.e., yeast Rad54 with AtRAD51 and yeast Rad51 with AtRad54) in a yeast two-hybrid experiment. These interactions hint at the molecular nature of this interkingdom complementation, although the stronger effect of the yeast Rad54 in plants than AtRad54 in yeast might be explained by an ability of the Rad54 protein to act alone, independently of its interaction with Rad51.
Li, Xiulei; Wang, Ling; Li, Yong; Song, Peiji
2017-10-01
This study aimed to investigate the value of diffusion-weighted imaging (DWI) in combination with conventional magnetic resonance imaging (MRI) for improving tumor detection in young patients treated with fertility-sparing surgery because of early cervical carcinoma. Fifty-four patients with stage Ia or Ib1 cervical carcinoma were enrolled into this study. Magnetic resonance examinations were performed for these patients using conventional MRI (including T1-weighted imaging, T2-weighted imaging, and dynamic contrast-enhanced MRI) and DWI. The apparent diffusion coefficient (ADC) values of cervical carcinoma were analyzed quantitatively and compared with that of adjacent epithelium. Sensitivity, positive predictive value, and accuracy of 2 sets of MRI sequences were calculated on the basis of histologic results, and the diagnostic ability of conventional MRI/DWI combinations was compared with that of conventional MRI. The mean ADC value from cervical carcinoma (mean, 786 × 10 mm/s ± 100) was significantly lower than that from adjacent epithelium (mean, 1352 × 10 mm/s ± 147) (P = 0.01). When the threshold ADC value set as 1010 × 10 mm/s, the sensitivity and specificity for differentiating cervical carcinoma from nontumor epithelium were 78.2% and 67.2%, respectively. The sensitivity and accuracy of conventional MRI for tumor detection were 76.0% and 70.4%, whereas the sensitivity and accuracy of conventional MRI/DWI combinations were 91.7% and 90.7%, respectively. Conventional MRI/DWI combinations revealed a positive predictive value of 97.8% and only 4 false-negative findings. The addition of DWI to conventional MRI considerably improves the sensitivity and accuracy of tumor detection in young patients treated with fertility-sparing surgery, which supports the inclusion quantitative analysis of ADC value in routine MRI protocol before fertility-sparing surgery.
Analysis of Particulate Contamination During Launch of MMS Mission
NASA Technical Reports Server (NTRS)
Brieda, Lubos; Barrie, Alexander; Hughes, David; Errigo, Therese
2010-01-01
NASA's Magnetospheric MultiScale (MMS) is an unmanned constellation of four identical spacecraft designed to investigate magnetic reconnection by obtaining detailed measurements of plasma properties in Earth's magnetopause and magnetotail. Each of the four identical satellites carries a suite of instruments which characterize the ambient ion and electron energy spectrum and composition. Some of these instruments utilize microchannel plates and are sensitive to particulate contamination. In this paper, we analyze the transport of particulates during pre-launch, launch and ascent events, and use the analysis to obtain quantitative predictions of contamination impact on the instruments. Viewfactor calculation is performed by considering the gravitational and aerodynamic forces acting on the particles.
Determining the Thickness and the Sub-Structure Details of the Magnetopause from MMS Data
NASA Astrophysics Data System (ADS)
Manuzzo, R.; Belmont, G.; Rezeau, L.
2017-12-01
The magnetopause thickness, like its mean location, is a notion that can have different meanings depending which parameters are considered (magnetic field or plasma properties). In any case, all the determinations have been done, up to now, considering the magnetopause boundary as a structure strictly stationary and 1D (or with a simple curvature). These determinations have shown to be very sensitive to the accuracy of the normal direction, because it affects the projection of the quantities of interest in studying geometrical sensitive phenomena such as the magnetic reconnection. Furthermore, the 1D stationary assumptions are likely to be rarely verified at the real magnetopause. The high quality measurements of MMS and their high time resolution now allow investigating the magnetopause structure in its more delicate features and with an unequal spatio-temporal accuracy. We make use here of the MDD tool developed by [Shi et al., 2005], which gives the dimensionality of the gradients from the four-point measurements of MMS and allows estimating the direction of the local normal when defined. Extending this method to various quantities, we can draw their profiles as functions of a physical abscissa (length instead of time) along a sensible normal. This procedure allows answering quantitatively the questions concerning the locations and the thicknesses of the different sub-structures encountered inside the "global magnetopause" [Rezeau, 2017, paper submitted to JGR-Space Physics].
Evidence that tRNA modifying enzymes are important in vivo targets for 5-fluorouracil in yeast
Gustavsson, Marie; Ronne, Hans
2008-01-01
We have screened a collection of haploid yeast knockout strains for increased sensitivity to 5-fluorouracil (5-FU). A total of 138 5-FU sensitive strains were found. Mutants affecting rRNA and tRNA maturation were particularly sensitive to 5-FU, with the tRNA methylation mutant trm10 being the most sensitive mutant. This is intriguing since trm10, like many other tRNA modification mutants, lacks a phenotype under normal conditions. However, double mutants for nonessential tRNA modification enzymes are frequently temperature sensitive, due to destabilization of hypomodified tRNAs. We therefore tested if the sensitivity of our mutants to 5-FU is affected by the temperature. We found that the cytotoxic effect of 5-FU is strongly enhanced at 38°C for tRNA modification mutants. Furthermore, tRNA modification mutants show similar synthetic interactions for temperature sensitivity and sensitivity to 5-FU. A model is proposed for how 5-FU kills these mutants by reducing the number of tRNA modifications, thus destabilizing tRNA. Finally, we found that also wild-type cells are temperature sensitive at higher concentrations of 5-FU. This suggests that tRNA destabilization contributes to 5-FU cytotoxicity in wild-type cells and provides a possible explanation why hyperthermia can enhance the effect of 5-FU in cancer therapy. PMID:18314501
Cadmium-sensitive, cad1 mutants of Arabidopsis thaliana are phytochelatin deficient.
Howden, R; Goldsbrough, P B; Andersen, C R; Cobbett, C S
1995-01-01
An allelic series of cad1, cadmium-sensitive mutants of Arabidopsis thaliana, was isolated. These mutants were sensitive to cadmium to different extents and were deficient in their ability to form cadmium-peptide complexes as detected by gel-filtration chromatography. Each mutant was deficient in its ability to accumulate phytochelatins (PCs) as detected by high-performance liquid chromatography and the amount of PCs accumulated by each mutant correlated with its degree of sensitivity to cadmium. The mutants had wild-type levels of glutathione, the substrate for PC biosynthesis, and in vitro assays demonstrated that each of the mutants was deficient in PC synthase activity. These results demonstrate conclusively the importance of PCs for cadmium tolerance in plants. PMID:7770517
Analysis of Poly(ADP-Ribose) Polymerases in Arabidopsis Telomere Biology
Townley, Jennifer M.; Shippen, Dorothy E.
2014-01-01
Maintaining the length of the telomere tract at chromosome ends is a complex process vital to normal cell division. Telomere length is controlled through the action of telomerase as well as a cadre of telomere-associated proteins that facilitate replication of the chromosome end and protect it from eliciting a DNA damage response. In vertebrates, multiple poly(ADP-ribose) polymerases (PARPs) have been implicated in the regulation of telomere length, telomerase activity and chromosome end protection. Here we investigate the role of PARPs in plant telomere biology. We analyzed Arabidopsis thaliana mutants null for PARP1 and PARP2 as well as plants treated with the PARP competitive inhibitor 3-AB. Plants deficient in PARP were hypersensitive to genotoxic stress, and expression of PARP1 and PARP2 mRNA was elevated in response to MMS or zeocin treatment or by the loss of telomerase. Additionally, PARP1 mRNA was induced in parp2 mutants, and conversely, PARP2 mRNA was induced in parp1 mutants. PARP3 mRNA, by contrast, was elevated in both parp1 and parp2 mutants, but not in seedlings treated with 3-AB or zeocin. PARP mutants and 3-AB treated plants displayed robust telomerase activity, no significant changes in telomere length, and no end-to-end chromosome fusions. Although there remains a possibility that PARPs play a role in Arabidopsis telomere biology, these findings argue that the contribution is a minor one. PMID:24551184
Zhao, Jinlei
2014-01-01
Monosaccharides available in the extracellular milieu of Agrobacterium tumefaciens can be transported into the cytoplasm, or via the periplasmic sugar binding protein, ChvE, play a critical role in controlling virulence gene expression. The ChvE-MmsAB ABC transporter is involved in the utilization of a wide range of monosaccharide substrates but redundant transporters are likely given the ability of a chvE-mmsAB deletion strain to grow, albeit more slowly, in the presence of particular monosaccharides. In this study, a putative ABC transporter encoded by the gxySBA operon is identified and shown to be involved in the utilization of glucose, xylose, fucose, and arabinose, which are also substrates for the ChvE-MmsAB ABC transporter. Significantly, GxySBA is also shown to be the first characterized glucosamine ABC transporter. The divergently transcribed gene gxyR encodes a repressor of the gxySBA operon, the function of which can be relieved by a subset of the transported sugars, including glucose, xylose, and glucosamine, and this substrate-induced expression can be repressed by glycerol. Furthermore, deletion of the transporter can increase the sensitivity of the virulence gene expression system to certain sugars that regulate it. Collectively, the results reveal a remarkably diverse set of substrates for the GxySBA transporter and its contribution to the repression of sugar sensitivity by the virulence-controlling system, thereby facilitating the capacity of the bacterium to distinguish between the soil and plant environments. PMID:24957625
Svensson, J Peter; Quirós Pesudo, Laia; McRee, Siobhan K; Adeleye, Yeyejide; Carmichael, Paul; Samson, Leona D
2013-01-01
Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N-nitrosourea (MNU), N,N'-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N-ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic 'barcode', were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput 'barcode' sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised.
Svensson, J. Peter; Quirós Pesudo, Laia; McRee, Siobhan K.; Adeleye, Yeyejide; Carmichael, Paul; Samson, Leona D.
2013-01-01
Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N-nitrosourea (MNU), N,N′-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N-ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic ‘barcode’, were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput ‘barcode’ sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised. PMID:24040048
The Magnetospheric Multiscale Mission
NASA Astrophysics Data System (ADS)
Burch, James
Magnetospheric Multiscale (MMS), a NASA four-spacecraft mission scheduled for launch in November 2014, will investigate magnetic reconnection in the boundary regions of the Earth’s magnetosphere, particularly along its dayside boundary with the solar wind and the neutral sheet in the magnetic tail. Among the important questions about reconnection that will be addressed are the following: Under what conditions can magnetic-field energy be converted to plasma energy by the annihilation of magnetic field through reconnection? How does reconnection vary with time, and what factors influence its temporal behavior? What microscale processes are responsible for reconnection? What determines the rate of reconnection? In order to accomplish its goals the MMS spacecraft must probe both those regions in which the magnetic fields are very nearly antiparallel and regions where a significant guide field exists. From previous missions we know the approximate speeds with which reconnection layers move through space to be from tens to hundreds of km/s. For electron skin depths of 5 to 10 km, the full 3D electron population (10 eV to above 20 keV) has to be sampled at rates greater than 10/s. The MMS Fast-Plasma Instrument (FPI) will sample electrons at greater than 30/s. Because the ion skin depth is larger, FPI will make full ion measurements at rates of greater than 6/s. 3D E-field measurements will be made by MMS once every ms. MMS will use an Active Spacecraft Potential Control device (ASPOC), which emits indium ions to neutralize the photoelectron current and keep the spacecraft from charging to more than +4 V. Because ion dynamics in Hall reconnection depend sensitively on ion mass, MMS includes a new-generation Hot Plasma Composition Analyzer (HPCA) that corrects problems with high proton fluxes that have prevented accurate ion-composition measurements near the dayside magnetospheric boundary. Finally, Energetic Particle Detector (EPD) measurements of electrons and composition-resolved ions at energies up to 500 keV are included, both as remote sensors of boundary regions and as diagnostics of the particle acceleration processes that are produced in reconnection. MMS will also be able to answer questions about the possible role of turbulence in increasing the reconnection rate. With a 1-ms time resolution for DC magnetic and electric fields, vector magnetic wave measurements up to 6 kHz, and 3-axis electric field measurements to 100 kHz, MMS will be able to measure the level of turbulence within the diffusion region. MMS includes a theory and modeling team that has provided the inputs required for an optimum experiment. A major issue is that MMS will make very high rate measurements that will exceed by far the available downlink capacity. For this reason, theory and modeling have been used to design a system that is able to evaluate data quality in near real time and select the most promising intervals for full downlink. This system will be implemented by a large, on-board computer memory and the capability to select intervals for downlink based on both the software’s sampling of the highest-rate data and the evaluation of lower-rate data by scientists on the ground.
Repair of Ultraviolet Radiation Damage in Sensitive Mutants of Micrococcus radiodurans
Moseley, B. E. B.
1969-01-01
Various aspects of the repair of ultraviolet (UV) radiation-induced damage were compared in wild-type Micrococcus radiodurans and two UV-sensitive mutants. Unlike the wild type, the mutants are more sensitive to radiation at 265 nm than at 280 nm. The delay in deoxyribonucleic acid (DNA) synthesis following exposure to UV is about seven times as long in the mutants as in the wild type. All three strains excise UV-induced pyrimidine dimers from their DNA, although the rate at which cytosine-thymine dimers are excised is slower in the mutants. The three strains also mend the single-strand breaks that appear in the irradiated DNA as a result of dimer excision, although the process is less efficient in the mutants. It is suggested that the increased sensitivity of the mutants to UV radiation may be caused by a partial defect in the second step of dimer excision. PMID:5773016
30 CFR 243.100 - What standards must my MMS-specified surety instrument meet?
Code of Federal Regulations, 2010 CFR
2010-07-01
... instrument meet? 243.100 Section 243.100 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE... Bonding Requirements § 243.100 What standards must my MMS-specified surety instrument meet? (a) An MMS-specified surety instrument must be in a form specified in MMS instructions. MMS will give you written...
Ayyagari, R; Impellizzeri, K J; Yoder, B L; Gary, S L; Burgers, P M
1995-01-01
The saccharomyces cerevisiae proliferating cell nuclear antigen (PCNA), encoded by the POL30 gene, is essential for DNA replication and DNA repair processes. Twenty-one site-directed mutations were constructed in the POL30 gene, each mutation changing two adjacently located charged amino acids to alanines. Although none of the mutant strains containing these double-alanine mutations as the sole source of PCNA were temperature sensitive or cold sensitive for growth, about a third of the mutants showed sensitivity to UV light. Some of those UV-sensitive mutants had elevated spontaneous mutation rates. In addition, several mutants suppressed a cold-sensitive mutation in the CDC44 gene, which encodes the large subunit of replication factor C. A cold-sensitive mutant, which was isolated by random mutagenesis, showed a terminal phenotype at the restrictive temperature consistent with a defect in DNA replication. Several mutant PCNAs were expressed and purified from Escherichia coli, and their in vitro properties were determined. The cold-sensitive mutant (pol30-52, S115P) was a monomer, rather than a trimer, in solution. This mutant was deficient for DNA synthesis in vitro. Partial restoration of DNA polymerase delta holoenzyme activity was achieved at 37 degrees C but not at 14 degrees C by inclusion of the macromolecular crowding agent polyethylene glycol in the assay. The only other mutant (pol30-6, DD41,42AA) that showed a growth defect was partially defective for interaction with replication factor C and DNA polymerase delta but completely defective for interaction with DNA polymerase epsilon. Two other mutants sensitive to DNA damage showed no defect in vitro. These results indicate that the latter mutants are specifically impaired in one or more DNA repair processes whereas pol30-6 and pol30-52 mutants show their primary defects in the basic DNA replication machinery with probable associated defects in DNA repair. Therefore, DNA repair requires interactions between repair-specific protein(s) and PCNA, which are distinct from those required for DNA replication. PMID:7623835
30 CFR 1218.560 - How do I submit Form MMS-4444?
Code of Federal Regulations, 2011 CFR
2011-07-01
... 30 Mineral Resources 3 2011-07-01 2011-07-01 false How do I submit Form MMS-4444? 1218.560 Section... Service of Official Correspondence § 1218.560 How do I submit Form MMS-4444? A copy of Form MMS-4444 and..., signed form to the address designated on the Form MMS-4444 instructions. ...
Federal Register 2010, 2011, 2012, 2013, 2014
2011-04-15
... ID No. BOEM-2011-0010] BOEMRE Information Collection Activity; 1010-0141, Subpart D, Oil and Gas... to oil and gas drilling operations, and related forms. DATES: Submit written comments by June 14..., Subpart D, Oil and Gas Drilling Operations. BOEMRE Form(s): MMS-123, MMS-123S, MMS-124, MMS-125, MMS-133...
A cadmium-sensitive, glutathione-deficient mutant of Arabidopsis thaliana.
Howden, R; Andersen, C R; Goldsbrough, P B; Cobbett, C S
1995-01-01
The roots of the cadmium-sensitive mutant of Arabidopsis thaliana, cad1-1, become brown in the presence of cadmium. A new cadmium-sensitive mutant affected at a second locus, cad2, has been identified using this phenotype. Genetic analysis has grown that the sensitive phenotype is recessive to the wild type and segregates as a single Mendelian locus. Assays of cadmium accumulation by intact plants indicated that the mutant is deficient in its ability to sequester cadmium. Undifferentiated callus tissue was also cadmium sensitive, suggesting that the mutant phenotype is expressed at the cellular level. The level of cadmium-binding complexes formed in vivo was decreased compared with the wild type and accumulation of phytochelatins was about 10% of that in the wild type. The level of glutathione, the substrate for phytochelatin biosynthesis, in tissues of the mutant was decreased to about 15 to 30% of that in the wild type. Thus, the deficiency in phytochelatin biosynthesis can be explained by a deficiency in glutathione. PMID:7770518
The FIELDS Instrument Suite on MMS: Scientific Objectives, Measurements, and Data Products
NASA Astrophysics Data System (ADS)
Torbert, R. B.; Russell, C. T.; Magnes, W.; Ergun, R. E.; Lindqvist, P.-A.; Le Contel, O.; Vaith, H.; Macri, J.; Myers, S.; Rau, D.; Needell, J.; King, B.; Granoff, M.; Chutter, M.; Dors, I.; Olsson, G.; Khotyaintsev, Y. V.; Eriksson, A.; Kletzing, C. A.; Bounds, S.; Anderson, B.; Baumjohann, W.; Steller, M.; Bromund, K.; Le, Guan; Nakamura, R.; Strangeway, R. J.; Leinweber, H. K.; Tucker, S.; Westfall, J.; Fischer, D.; Plaschke, F.; Porter, J.; Lappalainen, K.
2016-03-01
The FIELDS instrumentation suite on the Magnetospheric Multiscale (MMS) mission provides comprehensive measurements of the full vector magnetic and electric fields in the reconnection regions investigated by MMS, including the dayside magnetopause and the night-side magnetotail acceleration regions out to 25 Re. Six sensors on each of the four MMS spacecraft provide overlapping measurements of these fields with sensitive cross-calibrations both before and after launch. The FIELDS magnetic sensors consist of redundant flux-gate magnetometers (AFG and DFG) over the frequency range from DC to 64 Hz, a search coil magnetometer (SCM) providing AC measurements over the full whistler mode spectrum expected to be seen on MMS, and an Electron Drift Instrument (EDI) that calibrates offsets for the magnetometers. The FIELDS three-axis electric field measurements are provided by two sets of biased double-probe sensors (SDP and ADP) operating in a highly symmetric spacecraft environment to reduce significantly electrostatic errors. These sensors are complemented with the EDI electric measurements that are free from all local spacecraft perturbations. Cross-calibrated vector electric field measurements are thus produced from DC to 100 kHz, well beyond the upper hybrid resonance whose frequency provides an accurate determination of the local electron density. Due to its very large geometric factor, EDI also provides very high time resolution (˜1 ms) ambient electron flux measurements at a few selected energies near 1 keV. This paper provides an overview of the FIELDS suite, its science objectives and measurement requirements, and its performance as verified in calibration and cross-calibration procedures that result in anticipated errors less than 0.1 nT in B and 0.5 mV/m in E. Summaries of data products that result from FIELDS are also described, as well as algorithms for cross-calibration. Details of the design and performance characteristics of AFG/DFG, SCM, ADP, SDP, and EDI are provided in five companion papers.
Morphomic Malnutrition Score: A Standardized Screening Tool for Severe Malnutrition in Adults.
Lee, Christopher; Raymond, Erica; Derstine, Brian A; Glazer, Joshua M; Goulson, Rebecca; Rajasekaran, Avinash; Cherry-Bukowiec, Jill; Su, Grace L; Wang, Stewart C
2018-05-22
Granular diagnostic criteria for adult malnutrition are lacking. This study uses analytic morphomics to define the Morphomic Malnutrition Score (MMS), a robust screening tool for severe malnutrition. The study population (n = 643) consisted of 2 cohorts: 1) 124 emergency department patients diagnosed with severe malnutrition by a registered dietitian (RD) and an available computed tomography (CT) scan within 2 days of RD evaluation, and 2) 519 adult kidney donor candidates to represent a healthy cohort. Body composition markers of muscle area and abdominal adiposity were measured from patient CT scans using analytic morphomic assessment, and then converted to sex- and age-adjusted percentiles using the Reference Analytic Morphomics Population (RAMP). RAMP consists of 6000 patients chosen to be representative of the general population. The combined cohort was then randomly divided into training (n = 453) and validation (n = 190) sets. MMS was derived using logistic regression. The model coefficients were transformed into a score, normalized from 0 to 10 (10 = most severe). Severely malnourished patients had lower amounts of muscle and fat than kidney donors, specifically for dorsal muscle group area at the twelfth thoracic vertebral level (P < 0.001), psoas muscle area at the fourth lumbar vertebral level (P < 0.001), and subcutaneous fat area at the third lumbar vertebral level (P < 0.001)-all parameters in MMS. MMS for severely malnourished patients was higher than kidney donors (7.7 ± 2.2 vs 3.8 ± 2.0, respectively; P-value < 0.001). An MMS > 6.1 was accurate in determining nutrition diagnosis (82.1% sensitivity; 88.3% specificity; 85.2% balanced accuracy). MMS provides an evidence-based, granular assessment to distinguish severely malnourished adults from a healthy population. © 2018 American Society for Parenteral and Enteral Nutrition.
Díaz-Mejía, J Javier; Celaj, Albi; Mellor, Joseph C; Coté, Atina; Balint, Attila; Ho, Brandon; Bansal, Pritpal; Shaeri, Fatemeh; Gebbia, Marinella; Weile, Jochen; Verby, Marta; Karkhanina, Anna; Zhang, YiFan; Wong, Cassandra; Rich, Justin; Prendergast, D'Arcy; Gupta, Gaurav; Öztürk, Sedide; Durocher, Daniel; Brown, Grant W; Roth, Frederick P
2018-05-28
Condition-dependent genetic interactions can reveal functional relationships between genes that are not evident under standard culture conditions. State-of-the-art yeast genetic interaction mapping, which relies on robotic manipulation of arrays of double-mutant strains, does not scale readily to multi-condition studies. Here, we describe barcode fusion genetics to map genetic interactions (BFG-GI), by which double-mutant strains generated via en masse "party" mating can also be monitored en masse for growth to detect genetic interactions. By using site-specific recombination to fuse two DNA barcodes, each representing a specific gene deletion, BFG-GI enables multiplexed quantitative tracking of double mutants via next-generation sequencing. We applied BFG-GI to a matrix of DNA repair genes under nine different conditions, including methyl methanesulfonate (MMS), 4-nitroquinoline 1-oxide (4NQO), bleomycin, zeocin, and three other DNA-damaging environments. BFG-GI recapitulated known genetic interactions and yielded new condition-dependent genetic interactions. We validated and further explored a subnetwork of condition-dependent genetic interactions involving MAG1 , SLX4, and genes encoding the Shu complex, and inferred that loss of the Shu complex leads to an increase in the activation of the checkpoint protein kinase Rad53. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.
Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS.
Yao, Zhan; Yaeger, Rona; Rodrik-Outmezguine, Vanessa S; Tao, Anthony; Torres, Neilawattie M; Chang, Matthew T; Drosten, Matthias; Zhao, Huiyong; Cecchi, Fabiola; Hembrough, Todd; Michels, Judith; Baumert, Hervé; Miles, Linde; Campbell, Naomi M; de Stanchina, Elisa; Solit, David B; Barbacid, Mariano; Taylor, Barry S; Rosen, Neal
2017-08-10
Approximately 200 BRAF mutant alleles have been identified in human tumours. Activating BRAF mutants cause feedback inhibition of GTP-bound RAS, are RAS-independent and signal either as active monomers (class 1) or constitutively active dimers (class 2). Here we characterize a third class of BRAF mutants-those that have impaired kinase activity or are kinase-dead. These mutants are sensitive to ERK-mediated feedback and their activation of signalling is RAS-dependent. The mutants bind more tightly than wild-type BRAF to RAS-GTP, and their binding to and activation of wild-type CRAF is enhanced, leading to increased ERK signalling. The model suggests that dysregulation of signalling by these mutants in tumours requires coexistent mechanisms for maintaining RAS activation despite ERK-dependent feedback. Consistent with this hypothesis, melanomas with these class 3 BRAF mutations also harbour RAS mutations or NF1 deletions. By contrast, in lung and colorectal cancers with class 3 BRAF mutants, RAS is typically activated by receptor tyrosine kinase signalling. These tumours are sensitive to the inhibition of RAS activation by inhibitors of receptor tyrosine kinases. We have thus defined three distinct functional classes of BRAF mutants in human tumours. The mutants activate ERK signalling by different mechanisms that dictate their sensitivity to therapeutic inhibitors of the pathway.
Shin, Kwang-Soo; Park, Hee-Soo; Kim, Young; Heo, In-Beom; Kim, Young Hwan; Yu, Jae-Hyuk
2016-10-04
Aspergillus fumigatus reproduces and infects host by forming a high number of small asexual spores (conidia). The velvet proteins are global transcriptional regulators governing the complex process of conidiogenesis in this fungus. Here, to further understand the velvet-mediated regulation, we carried out comparative proteomic analyses of conidia of wild type (WT) and three velvet mutants (ΔveA, ΔvelB and ΔvosA). Cluster analysis of 184 protein spots showing at least 1.5-fold differential accumulation between WT and mutants reveal the clustering of WT- ΔveA and ΔvelB-ΔvosA. Among 43 proteins identified by Nano-LC-ESI-MS/MS, 23 including several heat shock proteins showed more than two-fold reduction in both the ∆velB and ∆vosA conidia. On the contrary, three proteins exhibited more than five-fold increase in ∆veA only, including the putative RNA polymerase II degradation factor DefA. The deletion of defA resulted in a reduced number of conidia and restricted colony growth. In addition, the defA deletion mutant conidia showed hypersensitivity against the DNA damaging agents NQO and MMS, while the ΔveA mutant conidia were more resistant against to NQO. Taken together, we propose that VeA controls protein level of DefA in conidia, which are dormant and equipped with multiple layers of protection against environmental cues. Copyright © 2016 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Noguchi, T.; Yabuta, H.; Itoh, S.; Sakamoto, N.; Mitsunari, T.; Okubo, A.; Okazaki, R.; Nakamura, T.; Tachibana, S.; Terada, K.; Ebihara, M.; Imae, N.; Kimura, M.; Nagahara, H.
2017-07-01
Micrometeorites (MMs) recovered from surface snow near the Dome Fuji Station, Antarctica are almost free from terrestrial weathering and contain very primitive materials, and are suitable for investigation of the evolution and interaction of inorganic and organic materials in the early solar system. We carried out a comprehensive study on seven porous and fluffy MMs [four Chondritic porous (CP) MMs and three fluffy fine-grained (Fluffy Fg) MMs] and one fine-grained type 1 (Fg C1) MM for comparison with scanning electron microscope, transmission electron microscope, X-ray absorption near-edge structure analysis, and secondary ion mass spectrometer. They show a variety of early aqueous activities. Four out of the seven CP MMs contain glass with embedded metal and sulfide (GEMS) and enstatite whiskers/platelets and do not have hydrated minerals. Despite the same mineralogy, organic chemistry of the CP MMs shows diversity. Two of them contain considerable amounts of organic materials with high carboxyl functionality, and one of them contains nitrile (Ctbnd N) and/or nitrogen heterocyclic groups with D and 15N enrichments, suggesting formation in the molecular cloud or a very low temperature region of the outer solar system. Another two CP MMs are poorer in organic materials than the above-mentioned MMs. Organic material in one of them is richer in aromatic C than the CP MMs mentioned above, being indistinguishable from those of hydrated carbonaceous chondrites. In addition, bulk chemical compositions of GEMS in the latter organic poor CP MMs are more homogeneous and have higher Fe/(Si + Mg + Fe) ratios than those of GEMS in the former organic-rich CP MMs. Functional group of the organic materials and amorphous silicate in GEMS in the organic-poor CP MMs may have transformed in the earliest stage of aqueous alteration, which did not form hydrated minerals. Three Fluffy Fg MMs contain abundant phyllosilicates, showing a clear evidence of aqueous alteration. Phyllosilicates in thee MMs are richer in Fe than those in hydrated IDPs, typical fine-grained hydrated (Fg C1) MMs, and hydrated carbonaceous chondrites. One of the Fluffy Fg MMs contains amorphous silicate, which is richer in Fe than GEMS and contains little or no nanophase Fe metal but contains Fe sulfide. Because the chemical compositions of the amorphous silicate are within the compositional field of GEMS in CP IDPs, the amorphous silicate may be alteration products of GEMS. The entire compositional field of GEMS in the CP MMs and the amorphous silicate in the Fluffy Fg MM matches that of the previously reported total compositional range of GEMS in IDPs. One Fluffy Fg MM contains Mg-rich phyllosilicate along with Fe-rich phyllosilicate and Mg-Fe carbonate. Mg-rich phyllosilicate and Mg-Fe carbonate may have been formed through the reaction of Fe-rich phyllosilicate, Mg-rich olivine and pyroxene, and water with C-bearing chemical species. These data indicate that CP MMs and Fluffy Fg MMs recovered from Antarctic surface snow contain materials that throw a light on the earliest stages of aqueous alteration on very primitive solar system bodies. Because mineralogy and isotopic and structural features of organic materials in D10IB009 are comparable with isotopically primitive IDPs, its parent body could be comets or icy asteroids showing mass ejection (active asteroids). By contrast, organic-poor CP MMs may have experienced the earliest stage of aqueous alteration and Fluffy Fg MMs experienced weak aqueous alteration. The precursor materials of the parent bodies of Fluffy Fg MMs probably contained abundant GEMS or GEMS-like materials like CP IDPs, which is common to fine-grained matrices of very primitive carbonaceous chondrites such as CR3s. However, highly porous nature of organic-poor CP MMs and Fluffy Fg MMs suggests that parent bodies of these MMs must have been much more porous than the parent bodies of primitive carbonaceous chondrites. Given no phyllosilicate among the returned samples of 81P/Wild 2 comet, the MMs may have been derived from porous icy asteroids such as active asteroids as well as P- and D-type asteroids rather than comets.
Burkhart, Katelyn A; Bruno, Alexander G; Bouxsein, Mary L; Bean, Jonathan F; Anderson, Dennis E
2018-01-01
Maximum muscle stress (MMS) is a critical parameter in musculoskeletal modeling, defining the maximum force that a muscle of given size can produce. However, a wide range of MMS values have been reported in literature, and few studies have estimated MMS in trunk muscles. Due to widespread use of musculoskeletal models in studies of the spine and trunk, there is a need to determine reasonable magnitude and range of trunk MMS. We measured trunk extension strength in 49 participants over 65 years of age, surveyed participants about low back pain, and acquired quantitative computed tomography (QCT) scans of their lumbar spines. Trunk muscle morphology was assessed from QCT scans and used to create a subject-specific musculoskeletal model for each participant. Model-predicted extension strength was computed using a trunk muscle MMS of 100 N/cm 2 . The MMS of each subject-specific model was then adjusted until the measured strength matched the model-predicted strength (±20 N). We found that measured trunk extension strength was significantly higher in men. With the initial constant MMS value, the musculoskeletal model generally over-predicted trunk extension strength. By adjusting MMS on a subject-specific basis, we found apparent MMS values ranging from 40 to 130 N/cm 2 , with an average of 75.5 N/cm 2 for both men and women. Subjects with low back pain had lower apparent MMS than subjects with no back pain. This work incorporates a unique approach to estimate subject-specific trunk MMS values via musculoskeletal modeling and provides a useful insight into MMS variation. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:498-505, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Code of Federal Regulations, 2010 CFR
2010-07-01
... same amount as Form MMS-2014 or bill document or to provide adequate information. 218.41 Section 218.41... Assessments for failure to submit payment of same amount as Form MMS-2014 or bill document or to provide... equivalent in amount to the total of individual line items on the associated Form MMS-2014, Form MMS-4430, or...
Ellouzi, Hasna; Hamed, Karim Ben; Cela, Jana; Müller, Maren; Abdelly, Chedly; Munné-Bosch, Sergi
2013-01-01
Recent studies suggest that tocopherols could play physiological roles in salt tolerance but the mechanisms are still unknown. In this study, we analyzed changes in growth, mineral and oxidative status in vte1 and vte4 Arabidopsis thaliana mutants exposed to salt stress. vte1 and vte4 mutants lack α-tocopherol, but only the vte1 mutant is additionally deficient in γ-tocopherol. Results showed that a deficiency in vitamin E leads to reduced growth and increased oxidative stress in hydroponically-grown plants. This effect was observed at early stages, not only in rosettes but also in roots. The vte1 mutant was more sensitive to salt-induced oxidative stress than the wild type and the vte4 mutant. Salt sensitivity was associated with (i) high contents of Na+, (ii) reduced efficiency of PSII photochemistry (Fv/Fm ratio) and (iii) more pronounced oxidative stress as indicated by increased hydrogen peroxide and malondialdeyde levels. The vte 4 mutant, which accumulates γ- instead of α-tocopherol showed an intermediate sensitivity to salt stress between the wild type and the vte1 mutant. Contents of abscisic acid, jasmonic acid and the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid were higher in the vte1 mutant than the vte4 mutant and wild type. It is concluded that vitamin E-deficient plants show an increased sensitivity to salt stress both in rosettes and roots, therefore indicating the positive role of tocopherols in stress tolerance, not only by minimizing oxidative stress, but also controlling Na+/K+ homeostasis and hormonal balance. PMID:23299430
Petrology and geochemistry of Antarctic micrometeorites
NASA Astrophysics Data System (ADS)
Kurat, Gero; Koeberl, Christian; Presper, Thomas; Brandstätter, Franz; Maurette, Michel
1994-09-01
The petrology and geochemistry of twentythree chondritic dust particles with masses of 1-47 μg (sizes 100-400 μm) were recovered from blue ice near Cap Prudhomme, Antarctica, and studied by INAA, ASEM, EMPA, and optical microscopy. Sample selection criteria were irregular shape and (for a subsample) black color, with the aim of studying as many unmelted micrometeorites (MMs) as possible. Of thirteen unmelted MMs, six were phyllosilicate-dominated MMs, and seven were coarsegrained crystalline MMs consisting mainly of olivine and pyroxene. The remaining ten particles were largely melted and consisted of a foamy melt with variable amounts of relic phases (scoriaceous MMs). Thus, of the black particles selected, an astonishing portion, 40% (by number), consisted of largely unmelted MMs. Although unmelted, most phyllosilicate MMs have been thermally metamorphosed to a degree that most of the phyllosilicates were destroyed, but not melted. The original preterrestrial mineralogy is occasionally preserved and consists of serpentine-like phyllosilicates with variable amounts of cronstedtite, tochilinite-like oxides, olivine, and pyroxene. The crystalline MMs consist of olivine, low-Ca pyroxene, tochilinite-like oxides, and occasional Ni-poor metal. Relics in scoriaceous MMs consist of the same phases. Mineral compositions and the coexistence of phyllosilicates with anhydrous phases are typical of CM and CR-type carbonaceous chondrites. However, the olivine/pyroxene ratio (~ 1) and the lack of carbonates, sulfates, and of very Fe-poor, refractory element-rich olivines and pyroxenes sets the MMs apart from CM and CR chondrites. The bulk chemistry of the phyllosilicate MMs is similar to that of CM chondrites. However, several elements are either depleted (Ca, Ni, S, less commonly Na, Mg, and Mn) or enriched (K, Fe, As, Br, Rb, Sb, and Au) in MMs as compared to CM chondrites. Similar depletions and enrichments are also found in the scoriaceous MMs. We suggest that the depletions are probably due to terrestrial leaching of sulfates and carbonates from unmelted MMs. The overabundance of some elements may also be due to processes acting during atmospheric passage such as the recondensation of meteoric vapors in the high atmosphere. Most MMs are coated by magnetite of platy or octahedral habit, which is rich in Mg, Al, Si, Mn, and Ni. We interpret the magnetites to be products of recondensation processes in the high (>90 km) atmosphere, which are, therefore, probably the first refractory aerominerals identified.
30 CFR 1210.106 - Where can I find more information on how to complete these production reports?
Code of Federal Regulations, 2011 CFR
2011-07-01
...://www.mrm.mms.gov/ReportingServices/Handbooks/Handbks.htm or from ONRR at P.O. Box 17110, Denver... Forms MMS-4054 and MMS-4058 on our Internet Web site at http://www.mrm.mms.gov/ReportingServices/Forms...
30 CFR 206.113 - How will MMS identify market centers?
Code of Federal Regulations, 2010 CFR
2010-07-01
... Section 206.113 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT PRODUCT VALUATION Federal Oil § 206.113 How will MMS identify market centers? MMS periodically will publish in the Federal Register a list of market centers. MMS will monitor market activity and, if...
30 CFR 250.1507 - How will MMS measure training results?
Code of Federal Regulations, 2011 CFR
2011-07-01
... 30 Mineral Resources 2 2011-07-01 2011-07-01 false How will MMS measure training results? 250.1507 Section 250.1507 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND ENFORCEMENT... Control and Production Safety Training § 250.1507 How will MMS measure training results? MMS may...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-09-07
..., Oil Spill Financial Responsibility for Offshore Facilities. Forms: MMS-1016, MMS-1017, MMS-1018, MMS... 1996 (Pub. L. 104-324), provides at section 1016 that oil spill financial responsibility (OSFR) for... President. Section 1016 of OPA supersedes the offshore facility oil spill financial responsibility...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xie, Xueqian; Greuter, Marcel J. W.; Groen, Jaap M.
Purpose: Coronary artery calcium score, traditionally based on electrocardiography (ECG)-triggered computed tomography (CT), predicts cardiovascular risk. However, nontriggered CT is extensively utilized. The study-purpose is to evaluate the in vitro agreement in coronary calcium score between nontriggered thoracic CT and ECG-triggered cardiac CT.Methods: Three artificial coronary arteries containing calcifications of different densities (high, medium, and low), and sizes (large, medium, and small), were studied in a moving cardiac phantom. Two 64-detector CT systems were used. The phantom moved at 0–90 mm/s in nontriggered low-dose CT as index test, and at 0–30 mm/s in ECG-triggered CT as reference. Differences in calciummore » scores between nontriggered and ECG-triggered CT were analyzed by t-test and 95% confidence interval. The sensitivity to detect calcification was calculated as the percentage of positive calcium scores.Results: Overall, calcium scores in nontriggered CT were not significantly different to those in ECG-triggered CT (p > 0.05). Calcium scores in nontriggered CT were within the 95% confidence interval of calcium scores in ECG-triggered CT, except predominantly at higher velocities (≥50 mm/s) for the high-density and large-size calcifications. The sensitivity for a nonzero calcium score was 100% for large calcifications, but 46%± 11% for small calcifications in nontriggered CT.Conclusions: When performing multiple measurements, good agreement in positive calcium scores is found between nontriggered thoracic and ECG-triggered cardiac CT. Agreement decreases with increasing coronary velocity. From this phantom study, it can be concluded that a high calcium score can be detected by nontriggered CT, and thus, that nontriggered CT likely can identify individuals at high risk of cardiovascular disease. On the other hand, a zero calcium score in nontriggered CT does not reliably exclude coronary calcification.« less
Harwood, V J; Gordon, A S
1994-01-01
Extracellular proteins of wild-type Vibrio alginolyticus were compared with those of copper-resistant and copper-sensitive mutants. One copper-resistant mutant (Cu40B3) constitutively produced an extracellular protein with the same apparent molecular mass (21 kDa) and chromatographic behavior as copper-binding protein (CuBP), a copper-induced supernatant protein which has been implicated in copper detoxification in wild-type V. alginolyticus. Copper-sensitive V. alginolyticus mutants displayed a range of alterations in supernatant protein profiles. CuBP was not detected in supernatants of one copper-sensitive mutant after cultures had been stressed with 50 microM copper. Increased resistance to copper was not induced by preincubation with subinhibitory levels of copper in the wild type or in the copper-resistant mutant Cu40B3. Copper-resistant mutants maintained the ability to grow on copper-amended agar after 10 or more subcultures on nonselective agar, demonstrating the stability of the phenotype. A derivative of Cu40B3 with wild-type sensitivity to copper which no longer constitutively expressed CuBP was isolated. The simultaneous loss of both constitutive CuBP production and copper resistance in Cu40B3 indicates that constitutive CuBP production is necessary for copper resistance in this mutant. These data support the hypothesis that the extracellular, ca. 20-kDa protein(s) of V. alginolyticus is an important factor in survival and growth of the organism at elevated copper concentrations. The range of phenotypes observed in copper-resistant and copper-sensitive V. alginolyticus indicate that altered sensitivity to copper was mediated by a variety of physiological changes. Images PMID:8031076
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-26
.... Forms: MMS-1016, 1017, 1018, 1019, 1020, 1021, and 1022. OMB Control Number: 1010-0106. Abstract: This... provide clarification, description, or explanation of these regulations, and forms MMS-1016 through MMS... section 1016 of Oil Pollution Act. The information is necessary to confirm that applicants can pay for...
30 CFR 204.204 - What accounting and auditing relief will MMS not allow?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What accounting and auditing relief will MMS... INTERIOR MINERALS REVENUE MANAGEMENT ALTERNATIVES FOR MARGINAL PROPERTIES Accounting and Auditing Relief § 204.204 What accounting and auditing relief will MMS not allow? MMS will not approve your request for...
30 CFR 285.613 - How will MMS process my SAP?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false How will MMS process my SAP? 285.613 Section 285.613 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE RENEWABLE... Requirements Contents of the Site Assessment Plan § 285.613 How will MMS process my SAP? (a) The MMS will...
30 CFR 285.648 - How will MMS process my GAP?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false How will MMS process my GAP? 285.648 Section 285.648 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE RENEWABLE... Requirements Contents of the General Activities Plan § 285.648 How will MMS process my GAP? (a) The MMS will...
30 CFR 206.62 - Does MMS protect information I provide?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Does MMS protect information I provide? 206.62 Section 206.62 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT PRODUCT VALUATION Indian Oil § 206.62 Does MMS protect information I provide? The MMS will keep...
Navigation Operations for the Magnetospheric Multiscale Mission
NASA Technical Reports Server (NTRS)
Long, Anne; Farahmand, Mitra; Carpenter, Russell
2015-01-01
The Magnetospheric Multiscale (MMS) mission employs four identical spinning spacecraft flying in highly elliptical Earth orbits. These spacecraft will fly in a series of tetrahedral formations with separations of less than 10 km. MMS navigation operations use onboard navigation to satisfy the mission definitive orbit and time determination requirements and in addition to minimize operations cost and complexity. The onboard navigation subsystem consists of the Navigator GPS receiver with Goddard Enhanced Onboard Navigation System (GEONS) software, and an Ultra-Stable Oscillator. The four MMS spacecraft are operated from a single Mission Operations Center, which includes a Flight Dynamics Operations Area (FDOA) that supports MMS navigation operations, as well as maneuver planning, conjunction assessment and attitude ground operations. The System Manager component of the FDOA automates routine operations processes. The GEONS Ground Support System component of the FDOA provides the tools needed to support MMS navigation operations. This paper provides an overview of the MMS mission and associated navigation requirements and constraints and discusses MMS navigation operations and the associated MMS ground system components built to support navigation-related operations.
Photonic metamaterials: a new class of materials for manipulating light waves
Iwanaga, Masanobu
2012-01-01
A decade of research on metamaterials (MMs) has yielded great progress in artificial electromagnetic materials in a wide frequency range from microwave to optical frequencies. This review outlines the achievements in photonic MMs that can efficiently manipulate light waves from near-ultraviolet to near-infrared in subwavelength dimensions. One of the key concepts of MMs is effective refractive index, realizing values that have not been obtained in ordinary solid materials. In addition to the high and low refractive indices, negative refractive indices have been reported in some photonic MMs. In anisotropic photonic MMs of high-contrast refractive indices, the polarization and phase of plane light waves were efficiently transformed in a well-designed manner, enabling remarkable miniaturization of linear optical devices such as polarizers, wave plates and circular dichroic devices. Another feature of photonic MMs is the possibility of unusual light propagation, paving the way for a new subfield of transfer optics. MM lenses having super-resolution and cloaking effects were introduced by exploiting novel light-propagating modes. Here, we present a new approach to describing photonic MMs definitely by resolving the electromagnetic eigenmodes. Two representative photonic MMs are addressed: the so-called fishnet MM slabs, which are known to have effective negative refractive index, and a three-dimensional MM based on a multilayer of a metal and an insulator. In these photonic MMs, we elucidate the underlying eigenmodes that induce unusual light propagations. Based on the progress of photonic MMs, the future potential and direction are discussed. PMID:27877512
Identification of Genes Related to Paulownia Witches’ Broom by AFLP and MSAP
Cao, Xibing; Fan, Guoqiang; Deng, Minjie; Zhao, Zhenli; Dong, Yanpeng
2014-01-01
DNA methylation is believed to play important roles in regulating gene expression in plant growth and development. Paulownia witches’ broom (PaWB) infection has been reported to be related to gene expression changes in paulownia plantlets. To determine whether DNA methylation is associated with gene expression changes in response to phytoplasma, we investigated variations in genomic DNA sequence and methylation in PaWB plantlets treated with methyl methane sulfonate (MMS) using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP) techniques, respectively. The results indicated that PaWB seedings recovered a normal morphology after treatment with more than 15 mg·L−1 MMS. PaWB infection did not cause changes of the paulownia DNA sequence at the AFLP level; However, DNA methylation levels and patterns were altered. Quantitative real-time PCR (qRT-PCR) showed that three of the methylated genes were up-regulated and three were down-regulated in the MMS-treated PaWB plantlets that had regained healthy morphology. These six genes might be involved in transcriptional regulation, plant defense, signal transduction and energy. The possible roles of these genes in PaWB are discussed. The results showed that changes of DNA methylation altered gene expression levels, and that MSAP might help identify genes related to PaWB. PMID:25196603
Identification of genes related to Paulownia witches' broom by AFLP and MSAP.
Cao, Xibing; Fan, Guoqiang; Deng, Minjie; Zhao, Zhenli; Dong, Yanpeng
2014-08-21
DNA methylation is believed to play important roles in regulating gene expression in plant growth and development. Paulownia witches' broom (PaWB) infection has been reported to be related to gene expression changes in paulownia plantlets. To determine whether DNA methylation is associated with gene expression changes in response to phytoplasma, we investigated variations in genomic DNA sequence and methylation in PaWB plantlets treated with methyl methane sulfonate (MMS) using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP) techniques, respectively. The results indicated that PaWB seedings recovered a normal morphology after treatment with more than 15 mg·L(-1) MMS. PaWB infection did not cause changes of the paulownia DNA sequence at the AFLP level; However, DNA methylation levels and patterns were altered. Quantitative real-time PCR (qRT-PCR) showed that three of the methylated genes were up-regulated and three were down-regulated in the MMS-treated PaWB plantlets that had regained healthy morphology. These six genes might be involved in transcriptional regulation, plant defense, signal transduction and energy. The possible roles of these genes in PaWB are discussed. The results showed that changes of DNA methylation altered gene expression levels, and that MSAP might help identify genes related to PaWB.
Furukawa, Tomoyuki; Angelis, Karel J.; Britt, Anne B.
2015-01-01
The DNA double-strand break (DSB) is a critical type of damage, and can be induced by both endogenous sources (e.g., errors of oxidative metabolism, transposable elements, programmed meiotic breaks, or perturbation of the DNA replication fork) and exogenous sources (e.g., ionizing radiation or radiomimetic chemicals). Although higher plants, like mammals, are thought to preferentially repair DSBs via nonhomologous end joining (NHEJ), much remains unclear about plant DSB repair pathways. Our reverse genetic approach suggests that DNA polymerase λ is involved in DSB repair in Arabidopsis. The Arabidopsis T-DNA insertion mutant (atpolλ-1) displayed sensitivity to both gamma-irradiation and treatment with radiomimetic reagents, but not to other DNA damaging treatments. The atpolλ-1 mutant showed a moderate sensitivity to DSBs, while Arabidopsis Ku70 and DNA ligase 4 mutants (atku70-3 and atlig4-2), both of which play critical roles in NHEJ, exhibited a hypersensitivity to these treatments. The atpolλ-1/atlig4-2 double mutant exhibited a higher sensitivity to DSBs than each single mutant, but the atku70/atpolλ-1 showed similar sensitivity to the atku70-3 mutant. We showed that transcription of the DNA ligase 1, DNA ligase 6, and Wee1 genes was quickly induced by BLM in several NHEJ deficient mutants in contrast to wild-type. Finally, the T-DNA transformation efficiency dropped in NHEJ deficient mutants and the lowest transformation efficiency was scored in the atpolλ-1/atlig4-2 double mutant. These results imply that AtPolλ is involved in both DSB repair and DNA damage response pathway. PMID:26074930
Tashiro, Takahiro; Okuyama, Hiroaki; Endo, Hiroko; Kawada, Kenji; Ashida, Yasuko; Ohue, Masayuki; Sakai, Yoshiharu; Inoue, Masahiro
2017-01-01
In clinic, cetuximab, an anti-EGFR antibody, improves treatment outcomes in colorectal cancer (CRC). KRAS-mutant CRC is generally resistant to cetuximab, although difference of the sensitivity among KRAS-mutants has not been studied in detail. We previously developed the cancer tissue-originated spheroid (CTOS) method, a primary culture method for cancer cells. We applied CTOS method to investigate whether ex vivo cetuximab sensitivity assays reflect the difference in sensitivity in the xenografts. Firstly, in vivo cetuximab treatment was performed with xenografts derived from 10 CTOS lines (3 KRAS-wildtype and 7 KRAS mutants). All two CTOS lines which exhibited tumor regression were KRAS-wildtype, meanwhile all KRAS-mutant CTOS lines grew more than the initial size: were resistant to cetuximab according to the clinical evaluation criteria, although the sensitivity was quite diverse. We divided KRAS-mutants into two groups; partially responsive group in which cetuximab had a substantial growth inhibitory effect, and resistant group which exhibited no effect. The ex vivo signaling assay with EGF stimulation revealed that the partially responsive group, but not the resistant group, exhibited suppressed ERK phosphorylation ex vivo. Furthermore, two lines from the partially responsive group, but none of the lines in the resistant group, exhibited a combinatory effect of cetuximab and trametinib, a MEK inhibitor, ex vivo and in vivo. Taken together, the results indicate that ex vivo signaling assay reflects the difference in sensitivity in vivo and stratifies KRAS mutant CTOS lines by sensitivity. Therefore, coupling the in vivo and ex vivo assays with CTOS can be a useful platform for understanding the mechanism of diversity in drug sensitivity. PMID:28301591
DOE Office of Scientific and Technical Information (OSTI.GOV)
Monaco, M.E.; Battista, T.A.; Gill, T.A.
1997-06-01
NOAA`s National Ocean Service (NOS) is developing a suite of desktop geographic information system (GIS) tools to define, assess, and solve coastal resource management issues. This paper describes one component of the emerging NOS Coastal and Ocean Assessment GIS: Environmental Sensitivity Index (ESI) data with emphasis on living marine resource information. This work is underway through a unique federal, state, and private-sector partnership. The desktop GIS is a versatile, user-friendly system designed to provide coastal managers with mapping and analysis capabilities. These functions are under development using the recently generated North Carolina ESI data, with emphasis on accessing, analyzing, andmore » mapping estuarine species distributions. Example system features include: a user-friendly front end, generation of ESI maps and tables, and custom spatial and temporal analyses. Partners in the development of the desktop system include: NOAA`s Office of Ocean Resources Conservation and Assessment (ORCA) and Coastal Services Center, the Minerals Management Service (MMS), Florida Marine Research Institute, Environmental Systems Research Institute, Inc., and Research Planning, Inc. This work complements and supports MMS`s Gulf-wide Information System designed to support oil-spill contingency planning.« less
Hama, S; Kimura, G
1980-01-01
Eleven temperature-sensitive mutants of adenovirus type 12, capable of forming plaques in human cells at 33 C but not at 39.5 C, were isolated from a stock of a wild-type strain after treatment with either nitrous acid or hydroxylamine. Complementation tests in doubly infected human cells permitted a tentative assignment of eight of these mutants to six complementation groups. Temperature-shift experiments revealed that one mutant is affected early and most of the other mutants are affected late. Only the early mutant, H12ts505, was temperature sensitive in viral DNA replication. Infectious virions of all the mutants except H12ts505 and two of the late mutants produced at 33 C, appeared to be more heat labile than those of the wild type. Only H12ts505 was temperature sensitive for the establishment of transformation of rat 3Y1 cells. One of the late mutants (H12ts504) had an increased transforming ability at the permissive temperature. Results of temperature-shift transformation experiments suggest that a viral function affected in H12ts505 is required for "initiation" of transformation. Some of the growth properties of H12ts505-transformed cells were also temperature dependent, suggesting that a functional expression of a gene mutation in H12ts505 is required to maintain at least some aspects of the transformed state.
Yasutani, I.; Ozawa, S.; Nishida, T.; Sugiyama, M.; Komamine, A.
1994-01-01
Three temperature-sensitive mutants of Arabidopsis thaliana that were defective in the redifferentiation of shoots were isolated as tools for the study of organogenesis. M3 lines were constructed by harvesting M3 seeds separately from each M2 plant. Comparative examination of shoot redifferentiation in root explants of 2700 M3 lines at 22[deg]C (permissive temperature) and at 27[deg]C (restrictive temperature) led to the identification of seven temperature-sensitive mutant lines. Genetic tests of three of the seven mutant lines indicated that temperature-sensitive redifferentiation of shoots in these three lines resulted from single, nuclear, recessive mutations in three different genes, designated SRD1, SRD2, and SRD3. The morphology of root explants of srd mutants cultured at the restrictive temperature suggests that the products of these SRD genes function at different stages of the redifferentiation of shoots. PMID:12232244
Genome-wide bisulfite sensitivity profiling of yeast suggests bisulfite inhibits transcription.
Segovia, Romulo; Mathew, Veena; Tam, Annie S; Stirling, Peter C
2017-09-01
Bisulfite, in the form of sodium bisulfite or metabisulfite, is used commercially as a food preservative. Bisulfite is used in the laboratory as a single-stranded DNA mutagen in epigenomic analyses of DNA methylation. Recently it has also been used on whole yeast cells to induce mutations in exposed single-stranded regions in vivo. To understand the effects of bisulfite on live cells we conducted a genome-wide screen for bisulfite sensitive mutants in yeast. Screening the deletion mutant array, and collections of essential gene mutants we define a genetic network of bisulfite sensitive mutants. Validation of screen hits revealed hyper-sensitivity of transcription and RNA processing mutants, rather than DNA repair pathways and follow-up analyses support a role in perturbation of RNA transactions. We propose a model in which bisulfite-modified nucleotides may interfere with transcription or RNA metabolism when used in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.
Toh-E, Akio; Ohkusu, Misako; Shimizu, Kiminori; Yamaguchi, Masashi; Ishiwada, Naruhiko; Watanabe, Akira; Kamei, Katsuhiko
2017-12-01
We constructed deletion mutants of Cryptococcus neoformans var neoformans (serotype D) genes encoding late ergosterol biosynthetic pathway enzymes and found that the mutations enhanced susceptibility to various drugs including micafungin, one of the echinocandins, to which wild-type Cryptococcus strains show no susceptibility. Furthermore, through isolation of a mutant resistant to micafungin from a micafungin-sensitive erg mutant and genetic analysis of it, we found that the responsible mutation occurred in the hotspot 2 of FKS1 encoding β-1, 3-glucan synthase, indicating that micafungin inhibited the growth of the erg mutant via inhibiting Fks1 activity. Addition of ergosterol to the culture of the erg mutants recovered the resistance to micafungin, suggesting that the presence of ergosterol in membrane inhibits the accession of micafungin to its target. We found that a loss of one of genes encoding subunits of v-ATPase, VPH1, made Cryptococcus cells sensitive to micafungin. Our observation that the erg2 vph1 double mutant was more sensitive to micafungin than either single mutant suggests that these two genes act differently in becoming resistant to micafungin. The erg mutants allowed us to study the physiological significance of β-1, 3-glucan synthesis in C. neoformans; the inhibition of β-1, 3-glucan synthesis induced cell death and changes in cellular morphology. By observing the erg mutant cells recovering from the growth inhibition imposed by micafungin, we recognized β-1, 3-glucan synthesis would suppress filamentous growth in C. neoformans.
A fiber-optic water flow sensor based on laser-heated silicon Fabry-Pérot cavity
NASA Astrophysics Data System (ADS)
Liu, Guigen; Sheng, Qiwen; Resende Lisboa Piassetta, Geraldo; Hou, Weilin; Han, Ming
2016-05-01
A hot-wire fiber-optic water flow sensor based on laser-heated silicon Fabry-Pérot interferometer (FPI) has been proposed and demonstrated in this paper. The operation of the sensor is based on the convective heat loss to water from a heated silicon FPI attached to the cleaved enface of a piece of single-mode fiber. The flow-induced change in the temperature is demodulated by the spectral shifts of the reflection fringes. An analytical model based on the FPI theory and heat transfer analysis has been developed for performance analysis. Numerical simulations based on finite element analysis have been conducted. The analytical and numerical results agree with each other in predicting the behavior of the sensor. Experiments have also been carried to demonstrate the sensing principle and verify the theoretical analysis. Investigations suggest that the sensitivity at low flow rates are much larger than that at high flow rates and the sensitivity can be easily improved by increasing the heating laser power. Experimental results show that an average sensitivity of 52.4 nm/(m/s) for the flow speed range of 1.5 mm/s to 12 mm/s was obtained with a heating power of ~12 mW, suggesting a resolution of ~1 μm/s assuming a wavelength resolution of 0.05 pm.
30 CFR 1218.580 - When do I submit Form MMS-4444?
Code of Federal Regulations, 2012 CFR
2012-07-01
... 30 Mineral Resources 3 2012-07-01 2012-07-01 false When do I submit Form MMS-4444? 1218.580... Service of Official Correspondence § 1218.580 When do I submit Form MMS-4444? Initially, you must submit Form MMS-4444 by November 29, 2006, and subsequently, within 2 weeks of any change of your address. ...
30 CFR 218.580 - When do I submit Form MMS-4444?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false When do I submit Form MMS-4444? 218.580 Section 218.580 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE... Correspondence § 218.580 When do I submit Form MMS-4444? Initially, you must submit MMS Form-4444 by November 29...
30 CFR 1218.580 - When do I submit Form MMS-4444?
Code of Federal Regulations, 2011 CFR
2011-07-01
... 30 Mineral Resources 3 2011-07-01 2011-07-01 false When do I submit Form MMS-4444? 1218.580... Service of Official Correspondence § 1218.580 When do I submit Form MMS-4444? Initially, you must submit Form MMS-4444 by November 29, 2006, and subsequently, within 2 weeks of any change of your address. ...
Magnetospheric Multiscale (MMS)
2014-05-09
MMS Stacked – View of the fully stacked MMS prior to being bagged for vibration tests. Learn more about MMS at www.nasa.gov/mms Credit NASA/Chris Gunn The Magnetospheric Multiscale, or MMS, will study how the sun and the Earth's magnetic fields connect and disconnect, an explosive process that can accelerate particles through space to nearly the speed of light. This process is called magnetic reconnection and can occur throughout all space. 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
Attitude Ground System (AGS) For The Magnetospheric Multi-Scale (MMS) Mission
NASA Technical Reports Server (NTRS)
Raymond, Juan C.; Sedlak, Joseph E.; Vint, Babak
2015-01-01
The Magnetospheric Multiscale (MMS) mission is a Solar-Terrestrial Probe mission consisting of four identically instrumented spin-stabilized spacecraft flying in an adjustable pyramid-like formation around the Earth. The formation of the MMS spacecraft allows for three-dimensional study of the phenomenon of magnetic reconnection, which is the primary objective of the mission. The MMS spacecraft were launched early on March 13, 2015 GMT. Due to the challenging and very constricted attitude and orbit requirements for performing the science, as well as the need to maintain the spacecraft formation, multiple ground functionalities were designed to support the mission. These functionalities were incorporated into a ground system known as the Attitude Ground System (AGS). Various AGS configurations have been used widely to support a variety of three-axis-stabilized and spin-stabilized spacecraft missions within the NASA Goddard Space Flight Center (GSFC). The original MMS operational concept required the AGS to perform highly accurate predictions of the effects of environmental disturbances on the spacecraft orientation and to plan the attitude maneuvers necessary to stay within the science attitude tolerance. The orbit adjustment requirements for formation control drove the need also to perform calibrations that have never been done before in support of NASA GSFC missions. The MMS mission required support analysts to provide fast and accurately calibrated values of the inertia tensor, center of mass, and accelerometer bias for each MMS spacecraft. During early design of the AGS functionalities, a Kalman filter for estimating the attitude, body rates, center of mass, and accelerometer bias, using only star tracker and accelerometer measurements, was heavily analyzed. A set of six distinct filters was evaluated and considered for estimating the spacecraft attitude and body rates using star tracker data only. Four of the six filters are closely related and were compared during support of the Time History of Events and Macroscale Interactions during Substorms (THEMIS) and Space Technology-5 (ST-5) missions. These analyses exposed high dependency and sensitivity on the knowledge of the spacecraft inertia tensor for both body rates and accelerometer bias estimation. The conclusion of the analysis led to the design of an inertia tensor calibration technique using only star tracker data. The second most important result of the analysis was the design of two separate Kalman filters to estimate the spacecraft attitude and body rates and the accelerometer bias instead of a single combined filter. In this paper, the calibration results of the mass properties, as well as the performance of the spacecraft attitude and body rates filters using flight data are presented and compared against the mission requirements.
A novel sandwich-type traveling wave piezoelectric tracked mobile system.
Wang, Liang; Shu, Chengyou; Zhang, Quan; Jin, Jiamei
2017-03-01
In this paper, a novel sandwich-type traveling wave piezoelectric tracked mobile system was proposed, designed, fabricated and experimentally investigated. The proposed system exhibits the advantages of simple structure, high mechanical integration, lack of electromagnetic interference, and lack of lubrication requirement, and hence shows potential application to robotic rovers for planetary exploration. The tracked mobile system is comprised of a sandwich actuating mechanism and a metal track. The actuating mechanism includes a sandwich piezoelectric transducer and two annular parts symmetrically placed at either end of the transducer, while the metal track is tensioned along the outer surfaces of the annular parts. Traveling waves with the same rotational direction are generated in the two annular parts, producing the microscopic elliptical motions of the surface particles on the annular parts. In this situation, if the pre-load is applied properly, the metal track can be driven by friction force to achieve bidirectional movement. At first, the finite element method was adopted to conduct the modal analysis and harmonic response analysis of the actuating mechanism, and the vibration characteristics were measured to confirm the operating principle. Then the optimal driving frequency of the system prototype, namely 35.1kHz, was measured by frequency sensitivity experiments. At last, the mechanical motion characteristics of the prototype were investigated experimentally. The results show that the average motion speeds of the prototype in dual directions were as 72mm/s and 61.5mm/s under the excitation voltage of 500V RMS , respectively. The optimal loading weights of the prototype in bi-directions were 0.32kg and 0.24kg with a maximum speed of 59.5mm/s and 61.67mm/s at the driving voltage of 300V RMS , respectively. Copyright © 2016 Elsevier B.V. All rights reserved.
CHO-cell mutant with a defect in cytokinesis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thompson, L.H.; Lindl, P.A.
1976-01-01
In a selection procedure designed to enrich for temperature-sensitive mutant cells blocked in mitosis a CHO-cell mutant was isolated which has a defect in cytokinesis as the basis of its temperature-sensitive phenotype. Cultures of the mutant had an abnormally high percentage (ie, 34 percent) of polyploid cells at the permissive temperature of 34/sup 0/C and showed further increased frequencies of polyploidy as well as many multinucleated cells at 38.5/sup 0/ and 39.5/sup 0/. When the mutant cells were synchronized in metaphase by Colcemid arrest and then placed into fresh medium at nonpermissive temperature, they did not divide although the completionmore » of mitosis appeared cytologically normal. Ultrastructural examination by electron microscopy of such synchronized cells at telophase revealed no specific defects in cellular components other than failure of development of a normal midbody. The sensitivity of the mutant to cytochalasin B and to Colcemid was the same as for wild-type cells. This mutation behaved as recessive in tetraploid cell hybrids constructed by fusing the mutant with a CHO strain which was wild-type with respect to temperature sensitivity.« less
NASA Technical Reports Server (NTRS)
Asato, Y.
1972-01-01
Three independently isolated ultraviolet light sensitive (uvs) mutants of Anacystis nidulans were characterized. Strain uvs-1 showed the highest sensitivity to UV by its greatly reduced photoreactivation capacity following irradiation. Pretreatment with caffeine suppressed the dark-survival curve of strain uvs-1, thus indicating the presence of excision enzymes involved in dark repair. Under 'black' and 'white' illumination, strain uvs-1 shows photorecovery properties comparable with wild-type cultures. Results indicate that strains uvs-1, uvs-35, and uvs-88 are probably genetically distinct UV-sensitive mutants.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Habib, Ahmed G.K.; Masuda, Kenta; Yukawa, Masashi
Protection of telomere (Pot1) is a single-stranded telomere binding protein which is essential for chromosome ends protection. Fission yeast Rqh1 is a member of RecQ helicases family which has essential roles in the maintenance of genomic stability and regulation of homologous recombination. Double mutant between fission yeast pot1Δ and rqh1 helicase dead (rqh1-hd) maintains telomere by homologous recombination. In pot1Δ rqh1-hd double mutant, recombination intermediates accumulate near telomere which disturb chromosome segregation and make cells sensitive to microtubule inhibitors thiabendazole (TBZ). Deletion of chk1{sup +} or mutation of its kinase domain shortens the G2 of pot1Δ rqh1-hd double mutant andmore » suppresses both the accumulation of recombination intermediates and the TBZ sensitivity of that double mutant. In this study, we asked whether the long G2 is the reason for the TBZ sensitivity of pot1Δ rqh1-hd double mutant. We found that shortening the G2 of pot1Δ rqh1-hd double mutant by additional mutations of wee1 and mik1 or gain of function mutation of Cdc2 suppresses both the accumulation of recombination intermediates and the TBZ sensitivity of pot1Δ rqh1-hd double mutant. Our results suggest that long G2 of pot1Δ rqh1-hd double mutant may allow time for the accumulation of recombination intermediates which disturb chromosome segregation and make cells sensitive to TBZ. - Ηighlights: • We show link between long G2 and accumulation of toxic recombination intermediates. • Accumulation of recombination intermediates at telomere results in TBZ sensitivity. • Activation of DNA damage checkpoint worsens cells' viability in presence of TBZ.« less
30 CFR 285.615 - What other reports or notices must I submit to MMS under my approved SAP?
Code of Federal Regulations, 2010 CFR
2010-07-01
... MMS under my approved SAP? 285.615 Section 285.615 Mineral Resources MINERALS MANAGEMENT SERVICE... CONTINENTAL SHELF Plans and Information Requirements Activities Under An Approved Sap § 285.615 What other reports or notices must I submit to MMS under my approved SAP? (a) You must notify MMS in writing within...
Magnetospheric Multiscale (MMS)
2017-12-08
MMS Four Separate – View of all four spacecraft in the MMS Cleanroom getting prepared for stacking operations. Learn more about MMS at www.nasa.gov/mms Credit NASA/Chris Gunn The Magnetospheric Multiscale, or MMS, will study how the sun and the Earth's magnetic fields connect and disconnect, an explosive process that can accelerate particles through space to nearly the speed of light. This process is called magnetic reconnection and can occur throughout all space. 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
Van de Vreede, Melita; McGrath, Anne; de Clifford, Jan
2018-05-14
Objective. The aim of the present study was to identify and quantify medication errors reportedly related to electronic medication management systems (eMMS) and those considered likely to occur more frequently with eMMS. This included developing a new classification system relevant to eMMS errors. Methods. Eight Victorian hospitals with eMMS participated in a retrospective audit of reported medication incidents from their incident reporting databases between May and July 2014. Site-appointed project officers submitted deidentified incidents they deemed new or likely to occur more frequently due to eMMS, together with the Incident Severity Rating (ISR). The authors reviewed and classified incidents. Results. There were 5826 medication-related incidents reported. In total, 93 (47 prescribing errors, 46 administration errors) were identified as new or potentially related to eMMS. Only one ISR2 (moderate) and no ISR1 (severe or death) errors were reported, so harm to patients in this 3-month period was minimal. The most commonly reported error types were 'human factors' and 'unfamiliarity or training' (70%) and 'cross-encounter or hybrid system errors' (22%). Conclusions. Although the results suggest that the errors reported were of low severity, organisations must remain vigilant to the risk of new errors and avoid the assumption that eMMS is the panacea to all medication error issues. What is known about the topic? eMMS have been shown to reduce some types of medication errors, but it has been reported that some new medication errors have been identified and some are likely to occur more frequently with eMMS. There are few published Australian studies that have reported on medication error types that are likely to occur more frequently with eMMS in more than one organisation and that include administration and prescribing errors. What does this paper add? This paper includes a new simple classification system for eMMS that is useful and outlines the most commonly reported incident types and can inform organisations and vendors on possible eMMS improvements. The paper suggests a new classification system for eMMS medication errors. What are the implications for practitioners? The results of the present study will highlight to organisations the need for ongoing review of system design, refinement of workflow issues, staff education and training and reporting and monitoring of errors.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What information will MMS publish in the... information will MMS publish in the Proposed Sale Notice and Final Sale Notice? For each competitive lease sale, MMS will publish a Proposed Sale Notice and a Final Sale Notice in the Federal Register. In the...
30 CFR 206.361 - How will MMS determine whether my royalty or direct use fee payments are correct?
Code of Federal Regulations, 2010 CFR
2010-07-01
... electricity or the sale of a geothermal resource, in conducting reviews and audits MMS will examine whether... royalties or direct use fees that you report are subject to monitoring, review, and audit. The MMS may review and audit your data, and MMS will direct you to use a different measure of royalty value, gross...
30 CFR 1218.560 - How do I submit Form MMS-4444?
Code of Federal Regulations, 2012 CFR
2012-07-01
... 30 Mineral Resources 3 2012-07-01 2012-07-01 false How do I submit Form MMS-4444? 1218.560 Section... Service of Official Correspondence § 1218.560 How do I submit Form MMS-4444? You may obtain a copy of Form MMS-4444 and instructions from ONRR. This form is posted at http://www.onrr.gov/FM/Forms/default.htm...
Isolation and characterization of acid-sensitive mutants of Pediococcus acidilactici.
Kurdi, Peter; Smitinont, Thitapha; Valyasevi, Ruud
2009-02-01
Acid-sensitive mutants of Pediococcus acidilactici BCC 9545, a starter culture of the Thai fermented pork sausage nham, were isolated as spontaneous neomycin resistant mutants. The mutants generally produced less acid and acidified the culture media less than the parent strain in a 72 h culturing period. Interestingly, the ATPase activities of the mutants did not differ considerably from that of the parent strain in acidic conditions. It was also found that the internal pH values of the mutant strains were somewhat lower in neutral environment, while at pH 5.0 their internal pHs were significantly lower compared to the parent's. Inhibiting the H(+)-ATPase activities in energized cells by N,N'-dicyclohexyl carbodiimide also revealed that protons were leaking from the mutants at neutral pH, which increased under acidic conditions. In contrast, the parent strain exhibited a smaller proton leak and only under acidic conditions. The membrane fatty acid analysis of the mutants indicated that under acidic conditions the mutants had a significantly smaller major unsaturated/saturated fatty acids ratio ((C(18:1)+C(18:3n6))/(C(16:0)+C(18:0))) compared to the parent strain's membrane. Taken together, these observations suggest there is a reasonable possibility that the membrane fatty acid profile differences in the mutants resulted in their acid-sensitivity.
Langdon, Casey G.; Held, Matthew A.; Platt, James T.; Meeth, Katrina; Iyidogan, Pinar; Mamillapalli, Ramanaiah; Koo, Andrew B.; Klein, Michael; Liu, Zongzhi; Bosenberg, Marcus W.; Stern, David F.
2016-01-01
Summary BRAF inhibitors have revolutionized treatment of mutant BRAF metastatic melanomas. However, resistance develops rapidly following BRAF inhibitor treatment. We have found that BRAF-mutant melanoma cell lines are more sensitive than wild-type BRAF cells to the small molecule tyrosine kinase inhibitor dovitinib. Sensitivity is associated with inhibition of a series of known dovitinib targets. Dovitinib in combination with several agents inhibits growth more effectively than either agent alone. These combinations inhibit BRAF-mutant melanoma and colorectal carcinoma cell lines, including cell lines with intrinsic or selected BRAF inhibitor resistance. Hence, combinations of dovitinib with second agents are potentially effective therapies for BRAF-mutant melanomas, regardless of their sensitivity to BRAF inhibitors. PMID:25854919
Quantified sensitivity of lakes to record historic earthquakes: Implications for paleoseismology
NASA Astrophysics Data System (ADS)
Wilhelm, Bruno; Nomade, Jerome; Crouzet, Christian; Litty, Camille; Belle, Simon; Rolland, Yann; Revel, Marie; Courboulex, Françoise; Arnaud, Fabien; Anselmetti, Flavio S.
2015-04-01
Seismic hazard assessment is a challenging issue for modern societies. A key parameter to be estimated is the recurrence interval of damaging earthquakes. In moderately active seismo-tectonic regions, this requires the establishment of earthquake records long enough to be relevant, i.e. far longer than historical observations. Here we investigate how lake sediments can be used for this purpose and quantify the conditions that enable earthquake recording. For this purpose, (i) we studied nine lake-sediment sequences to reconstruct mass-movement chronicles in different settings of the French Alpine range and (ii) we compared the chronicles to the well-documented earthquake history over the last five centuries. The studied lakes are all small alpine-type lakes based directly on bedrock. All lake sequences have been studied following the same methodology; (i) a multi-core approach to well understand the sedimentary processes within the lake basins, (ii) a high-resolution lithological and grain-size characterization and (iii) a dating based on short-lived radionuclide measurements, lead contaminations and radiocarbon ages. We identified 40 deposits related to 26 mass-movement (MM) occurrences. 46% (12 on 26) of the MMs are synchronous in neighbouring lakes, supporting strongly an earthquake origin. In addition, the good agreement between MMs ages and historical earthquake dates suggests an earthquake trigger for 88% (23 on 26) of them. Related epicenters are always located at distances of less than 100 km from the lakes and their epicentral MSK intensity ranges between VII and IX. However, the number of earthquake-triggered MMs varies between lakes of a same region, suggesting a gradual sensitivity of the lake sequences towards earthquake shaking, i.e. distinct lake-sediment slope stabilities. The quantification of this earthquake sensitivity and the comparison to the lake system and sediment characteristics suggest that the primary factor explaining this variability is the sedimentation rate. Indeed, an increasing sedimentation rate implies an increasing sensitivity to earthquake shaking with a apparent threshold of 0.5-1 mm.yr-1. To improve the paleoseismic event catalogue, further studies in small alpine-type lakes are needed. They should (i) focus on lake systems with sedimentation rates ≥ 1mm.yr-1, (ii) consider inter-lakes correlation over less than 100 km for epicentral earthquake MSK intensity < IX and (iii) control carefully that no significant change in sedimentation rates occurs within the record, which could falsify recurrence-interval assessment.
Bird, Scott M.; Rawlings, Andrea E.; Galloway, Johanna M.
2016-01-01
Magnetotactic bacteria are able to synthesise precise nanoparticles of the iron oxide magnetite within their cells. These particles are formed in dedicated organelles termed magnetosomes. These lipid membrane compartments use a range of biomineralisation proteins to nucleate and regulate the magnetite crystallisation process. A key component is the membrane protein Mms6, which binds to iron ions and helps to control the formation of the inorganic core. We have previously used Mms6 on gold surfaces patterned with a self-assembled monolayer to successfully produce arrays of magnetic nanoparticles. Here we use this surface system as a mimic of the interior face of the magnetosome membrane to study differences between intact Mms6 and the acid-rich C-terminal peptide subregion of the Mms6 protein. When immobilised on surfaces, the peptide is unable to reproduce the particle size or homogeneity control exhibited by the full Mms6 protein in our experimental setup. Moreover, the peptide is unable to support anchoring of a dense array of nanoparticles to the surface. This system also allows us to deconvolute particle binding from particle nucleation, and shows that Mms6 particle binding is less efficient when supplied with preformed magnetite nanoparticles when compared to particles precipitated from solution in the presence of the surface immobilised Mms6. This suggests that Mms6 binds to iron ions rather than to magnetite surfaces in our system, and is perhaps a nucleating agent rather than a controller of magnetite crystal growth. The comparison between the peptide and the protein under identical experimental conditions indicates that the full length sequence is required to support the full function of Mms6 on surfaces. PMID:27019707
Diffusion Region's Structure at the Subsolar Magnetopause with MMS Data
NASA Astrophysics Data System (ADS)
Cozzani, G.; Retino, A.; Califano, F.; Alexandrova, A.; Catapano, F.; Fu, H.; Le Contel, O.; Khotyaintsev, Y. V.; Vaivads, A.; Ahmadi, N.; Lindqvist, P. A.; Breuillard, H.; Mirioni, L.; Ergun, R.; Torbert, R. B.; Giles, B. L.; Russell, C. T.; Nakamura, R.; Moore, T. E.; Fuselier, S. A.; Mauk, B.; Burch, J.
2017-12-01
Magnetic reconnection occurs in the magnetosphere in thin current sheets, where a change in the magneticfield topology leads to rapid conversion of magnetic energy into ion and electron energy. To allow for magneticfield reconfiguration, both ions and electrons have to become demagnetized in the ion and electron diffusionregions, respectively. MMS spacecraft observations at inter-spacecraft separation ˜ 10 km (correspondingto ˜ 5 d_e at the magnetopause) allow, for the first time, to make multi-point studies of the structure of theelectron diffusion region (EDR). We present MMS observations on January,27th 2017 of one magnetopausecrossing close to the subsolar point showing several signatures consistent with an EDR encounter nearbya magnetic field minimum. The proximity to the reconnection site is further substantiated by the FirstOrder Taylor Expansion (FOTE) method applied to the magnetic field data. Observations suggest that allspacecraft passed through the EDR. Despite of the small inter-spacecraft separation (7 km), the observationsshow important differences among spacecraft. We focus on the comparison between MMS3 and MMS4 sincethey show the most striking differences. MMS3 measures a stronger parallel electron heating and highercurrent densities than MMS4. Both satellites observe crescent-shaped electron distribution functions on themagnetospheric side but MMS4 observes them over a longer time interval. These observations suggest thatMMS3 is passing closer to the reconnection site than MMS4. The differences between the observations by thetwo spacecraft indicate that the EDR is rather structured over scales of a few electron inertial lengths. Wealso evaluate the Generalized Ohm's law and find that the electric field is mainly balanced by the divergenceof the electron pressure tensor while the electron inertia term is negligible.
Fredriksson, Ingemar; Larsson, Marcus; Nyström, Fredrik H.; Länne, Toste; Östgren, Carl J.; Strömberg, Tomas
2010-01-01
OBJECTIVE To compare the microcirculatory velocity distribution in type 2 diabetic patients and nondiabetic control subjects at baseline and after local heating. RESEARCH DESIGN AND METHODS The skin blood flow response to local heating (44°C for 20 min) was assessed in 28 diabetic patients and 29 control subjects using a new velocity-resolved quantitative laser Doppler flowmetry technique (qLDF). The qLDF estimates erythrocyte (RBC) perfusion (velocity × concentration), in a physiologically relevant unit (grams RBC per 100 g tissue × millimeters per second) in a fixed output volume, separated into three velocity regions: v <1 mm/s, v 1–10 mm/s, and v >10 mm/s. RESULTS The increased blood flow occurs in vessels with a velocity >1 mm/s. A significantly lower response in qLDF total perfusion was found in diabetic patients than in control subjects after heat provocation because of less high-velocity blood flow (v >10 mm/s). The RBC concentration in diabetic patients increased sevenfold for v between 1 and 10 mm/s, and 15-fold for v >10 mm/s, whereas no significant increase was found for v <1 mm/s. The mean velocity increased from 0.94 to 7.3 mm/s in diabetic patients and from 0.83 to 9.7 mm/s in control subjects. CONCLUSIONS The perfusion increase occurs in larger shunting vessels and not as an increase in capillary flow. Baseline diabetic patient data indicated a redistribution of flow to higher velocity regions, associated with longer duration of diabetes. A lower perfusion was associated with a higher BMI and a lower toe-to-brachial systolic blood pressure ratio. PMID:20393143
The Distribution of Interplanetary Dust Near 1-AU: An MMS Perspective
NASA Astrophysics Data System (ADS)
Adrian, M. L.; St Cyr, O. C.; Wilson, L. B., III; Schiff, C.; Sacks, L. W.; Chai, D. J.; Queen, S. Z.; Sedlak, J. E.
2017-12-01
The distribution of dust in the ecliptic plane in the vicinity of 1-AU has been inferred from impacts on the four Magnetospheric Multiscale (MMS) mission spacecraft as detected by the Acceleration Measurement System (AMS) during periods when no other spacecraft activities are in progress. Consisting of four identically instrumented spacecraft, with an inter-spacecraft separation ranging from 10-km to 400-km, the MMS constellation forms a dust "detector" with approximately four-times the collection area of any previous dust monitoring framework. Here we introduce the MMS-AMS and the inferred dust impact observations, provide a preliminary comparison of the MMS distribution of dust impacts to previously reported interplanetary dust distributions — namely those of the STEREO mission — and report on our initial comparison of the MMS distribution of dust impacts with known meteor showers.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false When may MMS or the Secretary extend or cancel... When may MMS or the Secretary extend or cancel a lease at the development and production stage? (a) MMS..., the Secretary will cancel the lease: (1) When the 5-year period in paragraph (a)(1) of this section...
Magnetospheric Multiscale (MMS) [video
2014-05-09
MMS Spacecraft Animation The Magnetospheric Multiscale (MMS) mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth's magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration, and turbulence. These processes occur in all astrophysical plasma systems but can be studied in situ only in our solar system and most efficiently only in Earth's magnetosphere, where they control the dynamics of the geospace environment and play an important role in the processes known as "space weather." Learn more about MMS at www.nasa.gov/mms Learn more about MMS at www.nasa.gov/mms Credit NASA/Goddard The Magnetospheric Multiscale, or MMS, will study how the sun and the Earth's magnetic fields connect and disconnect, an explosive process that can accelerate particles through space to nearly the speed of light. This process is called magnetic reconnection and can occur throughout all space. 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
Magnetospheric Multiscale (MMS)
2017-12-08
MMS Spacecraft Animation The Magnetospheric Multiscale (MMS) mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth's magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration, and turbulence. These processes occur in all astrophysical plasma systems but can be studied in situ only in our solar system and most efficiently only in Earth's magnetosphere, where they control the dynamics of the geospace environment and play an important role in the processes known as "space weather." Learn more about MMS at www.nasa.gov/mms Learn more about MMS at www.nasa.gov/mms Credit NASA/Chris Gunn The Magnetospheric Multiscale, or MMS, will study how the sun and the Earth's magnetic fields connect and disconnect, an explosive process that can accelerate particles through space to nearly the speed of light. This process is called magnetic reconnection and can occur throughout all space. 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
2015-02-04
CAPE CANAVERAL, Fla. – The first stage of the United Launch Alliance Atlas V rocket for NASA's Magnetospheric Multiscale mission, or MMS, is lifted into the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. MMS will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. MMS consists of four identical spacecraft that work together to provide the first three-dimensional view of this fundamental process, which occurs throughout the universe. Launch is set for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Jim Grossmann
2015-02-04
CAPE CANAVERAL, Fla. – A crane lifts the first stage of the United Launch Alliance Atlas V rocket for NASA's Magnetospheric Multiscale mission, or MMS, into the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. MMS will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. MMS consists of four identical spacecraft that work together to provide the first three-dimensional view of this fundamental process, which occurs throughout the universe. Launch is set for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Jim Grossmann
2015-02-04
CAPE CANAVERAL, Fla. – Workers supervise the lift of the first stage of the United Launch Alliance Atlas V rocket for NASA's Magnetospheric Multiscale mission, or MMS, into the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. MMS will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. MMS consists of four identical spacecraft that work together to provide the first three-dimensional view of this fundamental process, which occurs throughout the universe. Launch is set for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Jim Grossmann
2015-02-04
CAPE CANAVERAL, Fla. – The first stage of the United Launch Alliance Atlas V rocket for NASA's Magnetospheric Multiscale mission, or MMS, is lifted into the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. MMS will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. MMS consists of four identical spacecraft that work together to provide the first three-dimensional view of this fundamental process, which occurs throughout the universe. Launch is set for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Jim Grossmann
2015-02-04
CAPE CANAVERAL, Fla. – The first stage of the United Launch Alliance Atlas V rocket for NASA's Magnetospheric Multiscale mission, or MMS, arrives at the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. MMS will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. MMS consists of four identical spacecraft that work together to provide the first three-dimensional view of this fundamental process, which occurs throughout the universe. Launch is set for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Jim Grossmann
Turrell, Frances K.; Kerr, Emma M.; Gao, Meiling; Thorpe, Hannah; Doherty, Gary J.; Cridge, Jake; Shorthouse, David; Speed, Alyson; Samarajiwa, Shamith; Hall, Benjamin A.; Griffiths, Meryl; Martins, Carla P.
2017-01-01
Lung adenocarcinoma accounts for ∼40% of lung cancers, the leading cause of cancer-related death worldwide, and current therapies provide only limited survival benefit. Approximately half of lung adenocarcinomas harbor mutations in TP53 (p53), making these mutants appealing targets for lung cancer therapy. As mutant p53 remains untargetable, mutant p53-dependent phenotypes represent alternative targeting opportunities, but the prevalence and therapeutic relevance of such effects (gain of function and dominant-negative activity) in lung adenocarcinoma are unclear. Through transcriptional and functional analysis of murine KrasG12D-p53null, -p53R172H (conformational), and -p53R270H (contact) mutant lung tumors, we identified genotype-independent and genotype-dependent therapeutic sensitivities. Unexpectedly, we found that wild-type p53 exerts a dominant tumor-suppressive effect on mutant tumors, as all genotypes were similarly sensitive to its restoration in vivo. These data show that the potential of p53 targeted therapies is comparable across all p53-deficient genotypes and may explain the high incidence of p53 loss of heterozygosity in mutant tumors. In contrast, mutant p53 gain of function and their associated vulnerabilities can vary according to mutation type. Notably, we identified a p53R270H-specific sensitivity to simvastatin in lung tumors, and the transcriptional signature that underlies this sensitivity was also present in human lung tumors, indicating that this therapeutic approach may be clinically relevant. PMID:28790158
Tao, Cuilian; Zhu, Yufang
2014-11-07
Magnetic mesoporous silica (MMS) nanoparticles with controllable magnetization have been synthesized by encapsulating Fe3O4 nanoparticles in a mesoporous silica matrix. The structure, magnetic heating capacity and drug delivery ability of MMS nanoparticles were evaluated. The results showed that MMS nanoparticles had an average particle size of 150 nm and showed low cytotoxicity and efficient cell uptake ability. MMS nanoparticles exhibited a sustained drug release in the medium of pH 5.0, but a very slow release in the medium of pH 7.4. On the other hand, MMS nanoparticles could controllably generate heat to reach the hyperthermia temperature within a short time upon exposure to an alternating magnetic field due to the superparamagnetic behavior and controllable magnetization. Therefore, MMS nanoparticles could provide a promising multifunctional platform for the combination of chemotherapy and hyperthermia for cancer therapy.
Isolation and preliminary characterization of temperature-sensitive mutants of influenza virus.
Sugiura, A; Tobita, K; Kilbourne, E D
1972-10-01
Isolation of temperature-sensitive (ts) mutants was attempted from the WSN strain of influenza A virus which was grown and assayed in MDBK cells. After growth of wild-type virus in the presence of 5-fluorouracil, 15 ts mutants were selected for which the ratio of plaquing efficiency at 39.5 C to that at 33 C was 10(-3) or less. In pairwise crosses of ts mutants, recombination and complementation were either very efficient or undetectable. It is suggested, therefore, that the viral genome consists of physically discrete units and recombination occurs as an exchange of these units. All 15 mutants have been assigned with certainty into five recombination groups. Three mutants are suspected to be double mutants. Any two complementing mutants always recombined with each other, and noncomplementing mutants did not recombine. In physiological tests, mutants showed diverse patterns of functional defects at the nonpermissive temperature. However, it was not always possible to correlate these physiological defects with the results of genetic characterization.
2015-02-04
CAPE CANAVERAL, Fla. – The first stage of the United Launch Alliance Atlas V rocket for NASA's Magnetospheric Multiscale mission, or MMS, begins the short journey from the Atlas Spaceflight Operations Center, or ASOC, on Cape Canaveral Air Force Station in Florida to Space Launch Complex 41. MMS will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. MMS consists of four identical spacecraft that work together to provide the first three-dimensional view of this fundamental process, which occurs throughout the universe. Launch is set for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Jim Grossmann
2015-02-04
CAPE CANAVERAL, Fla. – Operations are underway at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida to lift the newly delivered first stage of a United Launch Alliance Atlas V rocket into the mobile service tower. The rocket will launch NASA's Magnetospheric Multiscale mission, or MMS. MMS will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. MMS consists of four identical spacecraft that work together to provide the first three-dimensional view of this fundamental process, which occurs throughout the universe. Launch is set for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Jim Grossmann
2015-02-04
CAPE CANAVERAL, Fla. – Operations are underway at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida to lift the newly delivered first stage of a United Launch Alliance Atlas V rocket into the mobile service tower. The rocket will launch NASA's Magnetospheric Multiscale mission, or MMS. MMS will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. MMS consists of four identical spacecraft that work together to provide the first three-dimensional view of this fundamental process, which occurs throughout the universe. Launch is set for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Jim Grossmann
2015-02-04
CAPE CANAVERAL, Fla. – The first stage of the United Launch Alliance Atlas V rocket for NASA's Magnetospheric Multiscale mission, or MMS, is in position on the launch platform in the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. MMS will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. MMS consists of four identical spacecraft that work together to provide the first three-dimensional view of this fundamental process, which occurs throughout the universe. Launch is set for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Jim Grossmann
2015-02-04
CAPE CANAVERAL, Fla. – The first stage of the United Launch Alliance Atlas V rocket for NASA's Magnetospheric Multiscale mission, or MMS, is positioned on the launch platform in the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. MMS will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. MMS consists of four identical spacecraft that work together to provide the first three-dimensional view of this fundamental process, which occurs throughout the universe. Launch is set for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Jim Grossmann
Ubiquitin ligase activity of TFIIH and the transcriptional response to DNA damage.
Takagi, Yuichiro; Masuda, Claudio A; Chang, Wei-Hau; Komori, Hirofumi; Wang, Dong; Hunter, Tony; Joazeiro, Claudio A P; Kornberg, Roger D
2005-04-15
Core transcription factor (TF) IIH purified from yeast possesses an E3 ubiquitin (Ub) ligase activity, which resides, at least in part, in a RING finger (RNF) domain of the Ssl1 subunit. Yeast strains mutated in the Ssl1 RNF domain are sensitive to ultraviolet (UV) light and to methyl methanesulfonate (MMS). This increased sensitivity to DNA-damaging agents does not reflect a deficiency in nucleotide excision repair. Rather, it correlates with reduced transcriptional induction of genes involved in DNA repair, suggesting that the E3 Ub ligase activity of TFIIH mediates the transcriptional response to DNA damage.
Servicers system demonstration plan and capability development
NASA Technical Reports Server (NTRS)
Bulboaca, M. A.; Cuseo, J. A.; Derocher, W. L., Jr.; Maples, R. W.; Reynolds, P. C.; Sterrett, R. A.
1985-01-01
A plan for the demonstration of the exchange of Multi-Mission Modular Spacecraft (MMS) modules using the servicer mechanism Engineering Test Unit (ETU) was prepared and executed. The plan included: establishment of requirements, conceptual design, selection of MMS spacecraft mockup configuration, selection of MMS module mockup configuration, evaluation of adequacy of ETU load capability, and selection of a stowage rack arrangement. The MMS module exchange demonstration mockup equipment was designed, fabricated, checked out, shipped, installed, and demonstrated.
Mahmoud, Khaled A; Abdel-Wahab, Ahmed; Zourob, Mohammed
2015-01-01
A new versatile electrochemical sensor based on poly(styrene-co-acrylic acid) PSA/SiO2/Fe3O4/AuNPs/lignin (L-MMS) modified glassy carbon electrode (GCE) was developed for the selective detection of trace trinitrotoluene (TNT) from aqueous media with high sensitivity. The fabricated magnetic microspheres were characterized by transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). L-MMS films were cast on the GCE surface to fabricate the TNT sensing electrode. The limit of detection (LOD) of TNT determined by the amperometric i-t curve reached 35 pM. The lignin film and well packed Fe3O4/AuNPs facilitated the pre-concentration of trace TNT on the electrode surface resulting in a fast amperometric response of 3 seconds near the detection limit. The high sensitivity and excellent catalytic activity of the modified electrode could be attributed to the lignin layer and highly packed Fe3O4/AuNPs on the electrode surface. The total recovery of TNT from tapwater and seawater matrices was 98% and 96%, respectively. The electrode film was highly stable after five repeated adsorption/desorption cycles. The new electrochemical sensing scheme provides a highly selective, sensitive and versatile assay for the in-situ detection of TNT in complex water media.
Conjunction Assessment Techniques and Operational Results from the Magnetospheric Multiscale Mission
NASA Technical Reports Server (NTRS)
Williams, Trevor; Carpenter, Russell; Farahmand, Mitra; Ottenstein, Neil; Demoret, Michael; Godine, Dominic
2017-01-01
This paper will describe the results that have been obtained to date during the MMS mission concerning conjunction assessment. MMS navigation makes use of a weak-signal GPS-based system: this allows signals to be received even when MMS is flying above the GPS orbits, producing a highly accurate determination of the four MMS orbits. This data is downlinked to the MMS Mission Operations Center (MOC) and used by the Flight Dynamics Operations Area (FDOA) for both maneuver design and conjunction assessment. The MMS fly in tetrahedron formations around apogee, in order to collect simultaneous particles and fields science data. The original plan was to fly tetrahedra between 10 and 160 km in size; however, after Phase 1a of the mission, the science team requested that smaller sizes be flown if feasible. After analysis (to be detailed in a companion paper), a new minimum size of 7 km was decided upon. Flying at this reduced scale size makes conjunction assessment between the MMS spacecraft even more important: the methods that are used by the MMS FDOA to address this problem will be described in the paper, and a summary given of the previous analyses that went into the development of these techniques. Details will also be given of operational experiences to date. Finally, two CA mitigation maneuver types that have been designed (but never yet required to actually be performed) will also be outlined.
Vijeepallam, Kamini; Pandy, Vijayapandi; Kunasegaran, Thubasni; Murugan, Dharmani D.; Naidu, Murali
2016-01-01
In this study, we investigated the antipsychotic-like effect of methanolic extract of Mitragyna speciosa leaf (MMS) using in vivo and ex vivo studies. In vivo studies comprised of apomorphine-induced climbing behavior, haloperidol-induced catalepsy, and ketamine-induced social withdrawal tests in mice whereas the ex vivo study was conducted utilizing isolated rat vas deferens preparation. Acute oral administration of MMS (50–500 mg/kg) showed an inverted bell-shaped dose-response in apomorphine-induced cage climbing behavior in mice. The effective inhibitory doses of MMS (75 and 100 mg/kg, p.o.) obtained from the apomorphine study was further tested on haloperidol (subcataleptic dose; 0.1 mg/kg, i.p.)-induced catalepsy in the mouse bar test. MMS (75 and 100 mg/kg, p.o.) significantly potentiated the haloperidol-induced catalepsy in mice. Interestingly, MMS at the same effective doses (75 and 100 mg/kg, p.o.) significantly facilitated the social interaction in ketamine-induced social withdrawal mice. Furthermore, MMS inhibited the dopamine-induced contractile response dose-dependently in the isolated rat vas deferens preparations. In conclusion, this investigation provides first evidence that MMS exhibits antipsychotic-like activity with potential to alleviate positive as well as negative symptoms of psychosis in mice. This study also suggests the antidopaminergic activity of MMS that could be responsible for alleviating positive symptoms of psychosis. PMID:27999544
NASA Astrophysics Data System (ADS)
Lv, Qing-yuan; Li, Xian-yi; Shen, Bao-de; Dai, Ling; Xu, He; Shen, Cheng-ying; Yuan, Hai-long; Han, Jin
2014-06-01
The phospholipid-bile salts-mixed micelles (PL-BS-MMs) are potent carriers used for oral absorption of drugs that are poorly soluble in water; however, there are many limitations associated with liquid formulations. In the current study, the feasibility of preparing the fast dissolving oral films (FDOFs) containing PL-BS-MMs was examined. FDOFs incorporated with Cucurbitacin B (Cu B)-loaded PL-sodium deoxycholate (SDC)-MMs have been developed and characterized. To prepare the MMs and to serve as the micellar carrier, a weight ratio of 1:0.8 and total concentration of 54 mg/mL was selected for the PL/SDC based on the size, size distribution, zeta potential, encapsulation efficiency, and morphology. The concentration of Cu B was determined to be 5 mg/mL. Results showed that a narrow size distributed nanomicelles with a mean particle size of 86.21 ± 6.11 nm and a zeta potential of -31.21 ± 1.17 mV was obtained in our optimized Cu B-PL/SDC-MMs formulation. FDOFs were produced by solvent casting method and the formulation with 50 mg/mL of pullulan and 40 mg/mL of PEG 400 were deemed based on the physico-mechanical properties. The FDOFs containing Cu B-PL/SDC-MMs were easily reconstituted in a transparent and clear solution giving back a colloidal system with spherical micelles in the submicron range. In the in vitro dissolution test, the FDOFs containing Cu B-PL/SDC-MMs showed an increased dissolution velocity markedly. The pharmacokinetics study showed that the FDOFs containing PL-SDC-MMs not only kept the absorption properties as same as the PL-SDC-MMs, but also significantly increased the oral bioavailability of Cu B compared to the Cu B suspension ( p < 0.05). This study showed that the FDOFs containing Cu B-PL/SDC-MMs could represent a novel platform for the delivery of poorly water-soluble drugs via oral administration. Furthermore, the integration with the FDOFs could also provide a simple and cost-effective manner for the solidification of PL-SDC-MMs.
Reduced gravitropic sensitivity in roots of a starch-deficient mutant of Nicotiana sylvestris
NASA Technical Reports Server (NTRS)
Kiss, J. Z.; Sack, F. D.
1989-01-01
Gravitropism was studied in seedlings of Nicotiana sylvestris Speg. et Comes wild-type (WT) and mutant NS 458 which has a defective plastid phosphoglucomutase (EC 2.7.5.1.). Starch was greatly reduced in NS 458 compared to the WT, but small amounts of starch were detected in rootcap columella cells in NS 458 by light and electron microscopy. The roots of WT are more sensitive to gravity than mutant NS 458 roots since: (1) in mutant roots, curvature was reduced and delayed in the time course of curvature; (2) curvature of mutant roots was 24-56% that of WT roots over the range of induction periods tested; (3) in intermittent-stimulation experiments, curvature of mutant roots was 37% or less than that of WT roots in all treatments tested. The perception time, determined by intermittent-stimulation experiments, was < or = 5 s for WT roots and 30-60 s for mutant roots. The growth rates for WT and NS 458 roots were essentially equal. These results and our previous results with WT and starchless mutant Arabidopsis roots (Kiss et al. 1989, Planta 177, 198-206) support the conclusions that a full complement of starch is necessary for full gravitropic sensitivity and that amyloplasts function in gravity perception. Since a presumed relatively small increase in plastid buoyant mass (N. sylvestris mutant versus Arabidopsis mutant) significantly improves the orientation of the N. sylvestris mutant roots, we suggest that plastids are the likeliest candidates to be triggering gravity perception in roots of both mutants.
Tolkachjov, Stanislav N; Hocker, Thomas L; Hochwalt, Phillip C; Camilleri, Michael J; Arpey, Christopher J; Brewer, Jerry D; Otley, Clark C; Roenigk, Randall K; Baum, Christian L
2015-02-01
Hidradenocarcinoma (HAC) is a rare malignant adnexal neoplasm with reported metastatic potential and undefined optimal treatment. To review clinical characteristics and outcomes of patients with HAC treated with Mohs micrographic surgery (MMS). The authors performed a retrospective chart review of patients with HAC treated by MMS at Mayo Clinic from 1993 to 2013, recording patient demographics, tumor characteristics, MMS stages to clearance, follow-up, recurrence, metastasis, and mortality. Ten patients underwent MMS for HAC more than 20 years. The average age was 62.8 years, with 6 females and 4 males. Occipital scalp was the most common location (40%), followed by extremities (30%) and face (20%). In 5 of 7 cases (71%), "cyst" was the working clinical diagnosis. The average preoperative lesion area was 3.18 cm, with an average of 1.5 MMS stages required for clearance. Mean postoperative follow-up was 7 years (range, 5-205 months). No tumors treated with MMS recurred, metastasized, or led to disease-related mortality. Mohs micrographic surgery seems to be a useful treatment modality for HAC. This is the largest reported series of HAC treated with MMS with long-term follow-up.
Restoration of gravitropic sensitivity in starch-deficient mutants of Arabidopsis by hypergravity
NASA Technical Reports Server (NTRS)
Fitzelle, K. J.; Kiss, J. Z.
2001-01-01
Despite the extensive study of plant gravitropism, there have been few experiments which have utilized hypergravity as a tool to investigate gravisensitivity in flowering plants. Previous studies have shown that starch-deficient mutants of Arabidopsis are less sensitive to gravity compared to the wild-type (WT). In this report, the question addressed was whether hypergravity could restore the sensitivity of starch-deficient mutants of Arabidopsis. The strains examined include a WT, a starchless mutant and a reduced-starch mutant. Vertical orientation studies with dark-grown seedlings indicate that increased centrifugal acceleration improves orientation relative to the acceleration vector for all strains, even the WT. For starchless roots, growth of seedlings under constant 5 g acceleration was required to restore orientation to the level of the WT at 1 g. In contrast, approximately 10 g was required to restore the orientation of the starchless mutant hypocotyls to a WT level at 1 g. Examination of plastid position in root cap columella cells of the starchless mutant revealed that the restoration of gravitropic sensitivity was correlated with the sedimentation of plastids toward the distal cell wall. Even in WT plants, hypergravity caused greater sedimentation of plastids and improved gravitropic capability. Collectively, these experiments support the hypothesis of a statolith-based system of gravity perception in plants. As far as is known, this is the first report to use hypergravity to study the mechanisms of gravitropism in Arabidopsis.
30 CFR 210.157 - What reports must I submit to suspend an MMS order under appeal?
Code of Federal Regulations, 2010 CFR
2010-07-01
...) General. Reporters/payors or other recipients of MMS Minerals Revenue Management (MRM) orders who appeal...://www.mrm.mms.gov/Law_R_D/FRNotices/ICR0122.htm. (c) Reporting address. You may submit the required...
Temperature-sensitive PSII: a novel approach for sustained photosynthetic hydrogen production.
Bayro-Kaiser, Vinzenz; Nelson, Nathan
2016-12-01
The need for energy and the associated burden are ever growing. It is crucial to develop new technologies for generating clean and efficient energy for society to avoid upcoming energetic and environmental crises. Sunlight is the most abundant source of energy on the planet. Consequently, it has captured our interest. Certain microalgae possess the ability to capture solar energy and transfer it to the energy carrier, H 2 . H 2 is a valuable fuel, because its combustion produces only one by-product: water. However, the establishment of an efficient biophotolytic H 2 production system is hindered by three main obstacles: (1) the hydrogen-evolving enzyme, [FeFe]-hydrogenase, is highly sensitive to oxygen; (2) energy conversion efficiencies are not economically viable; and (3) hydrogen-producing organisms are sensitive to stressful conditions in large-scale production systems. This study aimed to circumvent the oxygen sensitivity of this process with a cyclic hydrogen production system. This approach required a mutant that responded to high temperatures by reducing oxygen evolution. To that end, we randomly mutagenized the green microalgae, Chlamydomonas reinhardtii, to generate mutants that exhibited temperature-sensitive photoautotrophic growth. The selected mutants were further characterized by their ability to evolve oxygen and hydrogen at 25 and 37 °C. We identified four candidate mutants for this project. We characterized these mutants with PSII fluorescence, P700 absorbance, and immunoblotting analyses. Finally, we demonstrated that these mutants could function in a prototype hydrogen-producing bioreactor. These mutant microalgae represent a novel approach for sustained hydrogen production.
Varicella-zoster virus complements herpes simplex virus type 1 temperature-sensitive mutants.
Felser, J M; Straus, S E; Ostrove, J M
1987-01-01
Varicella-zoster virus (VZV) can complement temperature-sensitive mutants of herpes simplex virus. Of seven mutants tested, two, carrying mutations in the immediate-early ICP4 and ICP27 proteins, were complemented. This complementation was not seen in coinfections with adenovirus type 5 or cytomegalovirus. Following transfection into CV-1 cells, a DNA fragment containing the VZV short repeat sequence complemented the ICP4 mutant. These data demonstrate a functional relationship between VZV and herpes simplex virus and have allowed localization of a putative VZV immediate-early gene. PMID:3023701
2015-02-04
CAPE CANAVERAL, Fla. – Preparations are underway in the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida for the arrival of the first stage of a United Launch Alliance Atlas V rocket from the Atlas Spaceflight Operations Center, or ASOC. The rocket will launch NASA's Magnetospheric Multiscale mission, or MMS. MMS will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. MMS consists of four identical spacecraft that work together to provide the first three-dimensional view of this fundamental process, which occurs throughout the universe. Launch is set for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Jim Grossmann
2014-11-14
CAPE CANAVERAL, Fla. – A plaque affixed to the side of a Magnetospheric Multiscale, or MMS, observatory dedicates the mission to George S. Moore, now deceased, an engineer who was a beloved colleague and friend to the MMS team. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-11-14
CAPE CANAVERAL, Fla. – A plaque affixed to the side of a Magnetospheric Multiscale, or MMS, observatory dedicates the mission to Dr. John William Klein, now deceased, who served the MMS team as the standing review board chairman. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-11-14
CAPE CANAVERAL, Fla. – A plaque affixed to the side of a Magnetospheric Multiscale, or MMS, observatory dedicates the mission to Richard “Richy” D’Antonio, now deceased, in grateful appreciation for his dedicated service to NASA’s MMS mission. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair.
Tsuda, Masataka; Cho, Kosai; Ooka, Masato; Shimizu, Naoto; Watanabe, Reiko; Yasui, Akira; Nakazawa, Yuka; Ogi, Tomoo; Harada, Hiroshi; Agama, Keli; Nakamura, Jun; Asada, Ryuta; Fujiike, Haruna; Sakuma, Tetsushi; Yamamoto, Takashi; Murai, Junko; Hiraoka, Masahiro; Koike, Kaoru; Pommier, Yves; Takeda, Shunichi; Hirota, Kouji
2017-01-01
ALC1/CHD1L is a member of the SNF2 superfamily of ATPases carrying a macrodomain that binds poly(ADP-ribose). Poly(ADP-ribose) polymerase (PARP) 1 and 2 synthesize poly(ADP-ribose) at DNA-strand cleavage sites, promoting base excision repair (BER). Although depletion of ALC1 causes increased sensitivity to various DNA-damaging agents (H2O2, UV, and phleomycin), the role played by ALC1 in BER has not yet been established. To explore this role, as well as the role of ALC1's ATPase activity in BER, we disrupted the ALC1 gene and inserted the ATPase-dead (E165Q) mutation into the ALC1 gene in chicken DT40 cells, which do not express PARP2. The resulting ALC1-/- and ALC1-/E165Q cells displayed an indistinguishable hypersensitivity to methylmethane sulfonate (MMS), an alkylating agent, and to H2O2, indicating that ATPase plays an essential role in the DNA-damage response. PARP1-/- and ALC1-/-/PARP1-/- cells exhibited a very similar sensitivity to MMS, suggesting that ALC1 and PARP1 collaborate in BER. Following pulse-exposure to H2O2, PARP1-/- and ALC1-/-/PARP1-/- cells showed similarly delayed kinetics in the repair of single-strand breaks, which arise as BER intermediates. To ascertain ALC1's role in BER in mammalian cells, we disrupted the ALC1 gene in human TK6 cells. Following exposure to MMS and to H2O2, the ALC1-/- TK6 cell line showed a delay in single-strand-break repair. We therefore conclude that ALC1 plays a role in BER. Following exposure to H2O2, ALC1-/- cells showed compromised chromatin relaxation. We thus propose that ALC1 is a unique BER factor that functions in a chromatin context, most likely as a chromatin-remodeling enzyme.
30 CFR 210.201 - How do I submit Form MMS-4430, Solid Minerals Production and Royalty Report?
Code of Federal Regulations, 2010 CFR
2010-07-01
... Form MMS-4430 are available on our Internet reporting web site or you may contact us toll free at 1-888... MMS-4430 electronically using our Internet reporting web site unless you meet the conditions in...
30 CFR 1210.201 - How do I submit Form MMS-4430, Solid Minerals Production and Royalty Report?
Code of Federal Regulations, 2012 CFR
2012-07-01
... submitting Form MMS-4430 are available on our Internet reporting web site or you may contact us toll free at... submit Form MMS-4430 electronically using our Internet reporting web site unless you meet the conditions...
Burgos, Jose L; Patterson, Thomas L; Graff-Zivin, Joshua S; Kahn, James G; Rangel, M Gudelia; Lozada, M Remedios; Staines, Hugo; Strathdee, Steffanie A
2016-01-01
We evaluated the cost-effectiveness of combined single session brief behavioral intervention, either didactic or interactive (Mujer Mas Segura, MMS) to promote safer-sex and safer-injection practices among female sex workers who inject drugs (FSW-IDUs) in Tijuana (TJ) and Ciudad-Juarez (CJ) Mexico. Data for this analysis was obtained from a factorial RCT in 2008-2010 coinciding with expansion of needle exchange programs (NEP) in TJ, but not in CJ. A Markov model was developed to estimate the incremental cost per quality adjusted life year gained (QALY) over a lifetime time frame among a hypothetical cohort of 1,000 FSW-IDUs comparing a less intensive didactic vs. a more intensive interactive format of the MMS, separately for safer sex and safer injection combined behavioral interventions. The costs for antiretroviral therapy was not included in the model. We applied a societal perspective, a discount rate of 3% per year and currency adjusted to US$2014. A multivariate sensitivity analysis was performed. The combined and individual components of the MMS interactive behavioral intervention were compared with the didactic formats by calculating the incremental cost-effectiveness ratios (ICER), defined as incremental unit of cost per additional health benefit (e.g., HIV/STI cases averted, QALYs) compared to the next least costly strategy. Following guidelines from the World Health Organization, a combined strategy was considered highly cost-effective if the incremental cost per QALY gained fell below the gross domestic product per capita (GDP) in Mexico (equivalent to US$10,300). For CJ, the mixed intervention approach of interactive safer sex/didactic safer injection had an incremental cost-effectiveness ratio (ICER) of US$4,360 ($310-$7,200) per QALY gained compared with a dually didactic strategy. Using the dually interactive strategy had an ICER of US$5,874 ($310-$7,200) compared with the mixed approach. For TJ, the combination of interactive safer sex/didactic safer injection had an ICER of US$5,921 ($104-$9,500) per QALY compared with dually didactic. Strategies using the interactive safe injection intervention were dominated due to lack of efficacy advantage. The multivariate sensitivity analysis showed a 95% certainty that in both CJ and TJ the ICER for the mixed approach (interactive safer sex didactic safer injection intervention) was less than the GDP per capita for Mexico. The dual interactive approach met this threshold consistently in CJ, but not in TJ. In the absence of an expanded NEP in CJ, the combined-interactive formats of the MMS behavioral intervention is highly cost-effective. In contrast, in TJ where NEP expansion suggests that improved access to sterile syringes significantly reduced injection-related risks, the interactive safer-sex combined didactic safer-injection was highly cost-effective compared with the combined didactic versions of the safer-sex and safer-injection formats of the MMS, with no added benefit from the interactive safer-injection component.
KRAS Mutation Is a Predictor of Oxaliplatin Sensitivity in Colon Cancer Cells
Lin, Yu-Lin; Ou, Da-Liang; Lin, Liang-In; Tseng, Li-Hui; Chang, Yih-Leong; Yeh, Kun-Huei; Cheng, Ann-Lii
2012-01-01
Molecular biomarkers to determine the effectiveness of targeted therapies in cancer treatment have been widely adopted in colorectal cancer (CRC), but those to predict chemotherapy sensitivity remain poorly defined. We tested our hypothesis that KRAS mutation may be a predictor of oxaliplatin sensitivity in CRC. KRAS was knocked-down in KRAS-mutant CRC cells (DLD-1G13D and SW480G12V) by small interfering RNAs (siRNA) and overexpressed in KRAS-wild-type CRC cells (COLO320DM) by KRAS-mutant vectors to generate paired CRC cells. These paired CRC cells were tested by oxaliplatin, irinotecan and 5FU to determine the change in drug sensitivity by MTT assay and flow cytometry. Reasons for sensitivity alteration were further determined by western blot and real-time quantitative reverse transcriptase polymerase chain reaction (qRT -PCR). In KRAS-wild-type CRC cells (COLO320DM), KRAS overexpression by mutant vectors caused excision repair cross-complementation group 1 (ERCC1) downregulation in protein and mRNA levels, and enhanced oxaliplatin sensitivity. In contrast, in KRAS-mutant CRC cells (DLD-1G13D and SW480G12V), KRAS knocked-down by KRAS-siRNA led to ERCC1 upregulation and increased oxaliplatin resistance. The sensitivity of irinotecan and 5FU had not changed in the paired CRC cells. To validate ERCC1 as a predictor of sensitivity for oxaliplatin, ERCC1 was knocked-down by siRNA in KRAS-wild-type CRC cells, which restored oxaliplatin sensitivity. In contrast, ERCC1 was overexpressed by ERCC1-expressing vectors in KRAS-mutant CRC cells, and caused oxaliplatin resistance. Overall, our findings suggest that KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer cells by the mechanism of ERCC1 downregulation. PMID:23209813
Foury, F; Goffeau, A
1979-01-01
Five nuclear mutants enhancing the spontaneous mutation rate of mtDNA have been isolated in Saccharomyces cerevisiae. These mutators fall into five complementation groups and are located at five genetic loci different from rad50 to rad57 loci. Three mutants (gam1, gam2, and gam4), insensitive or weakly sensitive to gamma-rays, exhibit increased frequency of spontaneous production of mutants with large deletions of the mtDNA (p-) and of all tested mitochondrial drug-resistant mutants. Two other mutants (gam3 and gam5), highly sensitive to gamma-rays, increase only the mutation rate of particular alleles of the mtDNA. The mutant gam5 enhances only the production of p- and erythromycin-resistant clones. The mutant gam3 exhibits an enhanced rate of oligomycin-resistant clones as well as a collateral increase of nuclear mutability. The existence of gam3 and gam5 mutants indicates that at least two common steps control both nuclear DNA repair and the mutability of particular alleles of the mtDNA. However, the general spontaneous mutability of the mtDNA includes at least three steps not involved in the repair of nuclear DNA, as revealed by the gam1, gam2, and gam4 mutations. PMID:392521
Kang, Tina Manzhu; Yuan, Jessica; Nguyen, Angelyn; Becket, Elinne; Yang, Hanjing; Miller, Jeffrey H
2012-06-01
The distribution of mutants in the Keio collection of Escherichia coli gene knockout mutants that display increased sensitivity to the aminoglycosides kanamycin and neomycin indicates that damaged bases resulting from antibiotic action can lead to cell death. Strains lacking one of a number of glycosylases (e.g., AlkA, YzaB, Ogt, KsgA) or other specific repair proteins (AlkB, PhrB, SmbC) are more sensitive to these antibiotics. Mutants lacking AlkB display the strongest sensitivity among the glycosylase- or direct lesion removal-deficient strains. This perhaps suggests the involvement of ethenoadenine adducts, resulting from reactive oxygen species and lipid peroxidation, since AlkB removes this lesion. Other sensitivities displayed by mutants lacking UvrA, polymerase V (Pol V), or components of double-strand break repair indicate that kanamycin results in damaged base pairs that need to be removed or replicated past in order to avoid double-strand breaks that saturate the cellular repair capacity. Caffeine enhances the sensitivities of these repair-deficient strains to kanamycin and neomycin. The gene knockout mutants that display increased sensitivity to caffeine (dnaQ, holC, holD, and priA knockout mutants) indicate that caffeine blocks DNA replication, ultimately leading to double-strand breaks that require recombinational repair by functions encoded by recA, recB, and recC, among others. Additionally, caffeine partially protects cells of both Escherichia coli and Bacillus anthracis from killing by the widely used fluoroquinolone antibiotic ciprofloxacin.
30 CFR 285.201 - How will MMS issue leases?
Code of Federal Regulations, 2010 CFR
2010-07-01
....201 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE RENEWABLE ENERGY ALTERNATE USES OF EXISTING FACILITIES ON THE OUTER CONTINENTAL SHELF Issuance of OCS Renewable Energy Leases General Lease Information § 285.201 How will MMS issue leases? The MMS will issue leases on...
Akula, Sravani; Kamasani, Swapna; Sivan, Sree Kanth; Manga, Vijjulatha; Vudem, Dashavantha Reddy; Kancha, Rama Krishna
2018-05-01
A significant proportion of patients with lung cancer carry mutations in the EGFR kinase domain. The presence of a deletion mutation in exon 19 or L858R point mutation in the EGFR kinase domain has been shown to cause enhanced efficacy of inhibitor treatment in patients with NSCLC. Several less frequent (uncommon) mutations in the EGFR kinase domain with potential implications in treatment response have also been reported. The role of a limited number of uncommon mutations in drug sensitivity was experimentally verified. However, a huge number of these mutations remain uncharacterized for inhibitor sensitivity or resistance. A large-scale computational analysis of clinically reported 298 point mutants of EGFR kinase domain has been performed, and drug sensitivity profiles for each mutant toward seven kinase inhibitors has been determined by molecular docking. In addition, the relative inhibitor binding affinity toward each drug as compared with that of adenosine triphosphate was calculated for each mutant. The inhibitor sensitivity profiles predicted in this study for a set of previously characterized mutants correlated well with the published clinical, experimental, and computational data. Both the single and compound mutations displayed differential inhibitor sensitivity toward first- and next-generation kinase inhibitors. The present study provides predicted drug sensitivity profiles for a large panel of uncommon EGFR mutations toward multiple inhibitors, which may help clinicians in deciding mutant-specific treatment strategies. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
NASA Technical Reports Server (NTRS)
Mckim, Stephen A.
2016-01-01
This thesis describes the development and correlation of a thermal model that forms the foundation of a thermal capacitance spacecraft propellant load estimator. Specific details of creating the thermal model for the diaphragm propellant tank used on NASA's Magnetospheric Multiscale spacecraft using ANSYS and the correlation process implemented are presented. The thermal model was correlated to within plus or minus 3 degrees Celsius of the thermal vacuum test data, and was determined sufficient to make future propellant predictions on MMS. The model was also found to be relatively sensitive to uncertainties in applied heat flux and mass knowledge of the tank. More work is needed to improve temperature predictions in the upper hemisphere of the propellant tank where predictions were found to be 2 to 2.5 C lower than the test data. A road map for applying the model to predict propellant loads on the actual MMS spacecraft toward its end of life in 2017-2018 is also presented.
Lohße, Anna; Ullrich, Susanne; Katzmann, Emanuel; Borg, Sarah; Wanner, Gerd; Richter, Michael; Voigt, Birgit; Schweder, Thomas; Schüler, Dirk
2011-01-01
Bacterial magnetosomes are membrane-enveloped, nanometer-sized crystals of magnetite, which serve for magnetotactic navigation. All genes implicated in the synthesis of these organelles are located in a conserved genomic magnetosome island (MAI). We performed a comprehensive bioinformatic, proteomic and genetic analysis of the MAI in Magnetospirillum gryphiswaldense. By the construction of large deletion mutants we demonstrate that the entire region is dispensable for growth, and the majority of MAI genes have no detectable function in magnetosome formation and could be eliminated without any effect. Only <25% of the region comprising four major operons could be associated with magnetite biomineralization, which correlated with high expression of these genes and their conservation among magnetotactic bacteria. Whereas only deletion of the mamAB operon resulted in the complete loss of magnetic particles, deletion of the conserved mms6, mamGFDC, and mamXY operons led to severe defects in morphology, size and organization of magnetite crystals. However, strains in which these operons were eliminated together retained the ability to synthesize small irregular crystallites, and weakly aligned in magnetic fields. This demonstrates that whereas the mamGFDC, mms6 and mamXY operons have crucial and partially overlapping functions for the formation of functional magnetosomes, the mamAB operon is the only region of the MAI, which is necessary and sufficient for magnetite biomineralization. Our data further reduce the known minimal gene set required for magnetosome formation and will be useful for future genome engineering approaches. PMID:22043287
Kepp, Kasper P
2015-10-01
Fast and accurate computation of protein stability is increasingly important for e.g. protein engineering and protein misfolding diseases, but no consensus methods exist for important proteins such as globins, and performance may depend on the type of structural input given. This paper reports benchmarking of six protein stability calculators (POPMUSIC 2.1, I-Mutant 2.0, I-Mutant 3.0, CUPSAT, SDM, and mCSM) against 134 experimental stability changes for mutations of sperm-whale myoglobin. Six different high-resolution structures were used to test structure sensitivity that may impair protein calculations. The trend accuracy of the methods decreased as I-Mutant 2.0 (R=0.64-0.65), SDM (R=0.57-0.60), POPMUSIC2.1 (R=0.54-0.57), I-Mutant 3.0 (R=0.53-0.55), mCSM (R=0.35-0.47), and CUPSAT (R=0.25-0.48). The mean signed errors increased as SDM
30 CFR 218.560 - How do I submit Form MMS-4444?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 218.560 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT COLLECTION OF MONIES AND PROVISION FOR GEOTHERMAL CREDITS AND INCENTIVES Service of Official... from MMS. It will also be posted on the MMS Web site. Submit the completed, signed form to the address...
30 CFR 210.56 - Where can I find more information on how to complete the royalty report?
Code of Federal Regulations, 2010 CFR
2010-07-01
... Reporter Handbook. The handbook is available on our Internet Web site at http://www.mrm.mms.gov/Reporting...://www.mrm.mms.gov/ReportingServices/Forms/AFSOil_Gas.htm, or you may request the form from MMS at P.O...
30 CFR 206.365 - Does MMS protect information I provide?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Does MMS protect information I provide? 206.365 Section 206.365 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT PRODUCT VALUATION Geothermal Resources § 206.365 Does MMS protect information I provide? Certain...
30 CFR 206.108 - Does MMS protect information I provide?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Does MMS protect information I provide? 206.108 Section 206.108 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT PRODUCT VALUATION Federal Oil § 206.108 Does MMS protect information I provide? Certain...
The Modular Modeling System (MMS): User's Manual
Leavesley, G.H.; Restrepo, Pedro J.; Markstrom, S.L.; Dixon, M.; Stannard, L.G.
1996-01-01
The Modular Modeling System (MMS) is an integrated system of computer software that has been developed to provide the research and operational framework needed to support development, testing, and evaluation of physical-process algorithms and to facilitate integration of user-selected sets of algorithms into operational physical-process models. MMS uses a module library that contains modules for simulating a variety of water, energy, and biogeochemical processes. A model is created by selectively coupling the most appropriate modules from the library to create a 'suitable' model for the desired application. Where existing modules do not provide appropriate process algorithms, new modules can be developed. The MMS user's manual provides installation instructions and a detailed discussion of system concepts, module development, and model development and application using the MMS graphical user interface.
2014-10-29
CAPE CANAVERAL, Fla. – Two of the observatories, the lower stack, mini-stack number 1, for NASA's Magnetospheric Multiscale Observatory, or MMS, roll into the Building 1 airlock at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-11-13
CAPE CANAVERAL, Fla. – All four of the Magnetospheric Multiscale, or MMS, spacecraft have arrived in the Building 1 high bay of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the upper deck arrived Nov. 12; the two MMS spacecraft comprising the lower stack arrived Oct. 29. The Magnetospheric Multiscale mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
Detection of BRAF mutations from solid tumors using Tumorplex™ technology
Yo, Jacob; Hay, Katie S.L.; Vinayagamoorthy, Dilanthi; Maryanski, Danielle; Carter, Mark; Wiegel, Joseph; Vinayagamoorthy, Thuraiayah
2015-01-01
Allele specific multiplex sequencing (Tumorplex™) is a new molecular platform for the detection of single base mutation in tumor biopsies with high sensitivity for clinical testing. Tumorplex™ is a novel modification of Sanger sequencing technology that generates both mutant and wild type nucleotide sequences simultaneously in the same electropherogram. The molecular weight of the two sequencing primers are different such that the two sequences generated are separated, thus eliminating possible suppression of mutant signal by the more abundant wild type signal. Tumorplex™ platform technology was tested using BRAF mutation V600E. These studies were performed with cloned BRAF mutations and genomic DNA extracted from tumor cells carrying 50% mutant allele. The lower limit of detection for BRAF V600E was found to be 20 genome equivalents (GE) using genomic DNA extracted from mutation specific cell lines. Sensitivity of the assay was tested by challenging the mutant allele with wild type allele at 20 GE, and was able to detect BRAF mutant signal at a GE ration of 20:1 × 107 (mutant to wild-type). This level of sensitivity can detect low abundance of clonal mutations in tumor biopsies and eliminate the need for cell enrichment. • Tumorplex™ is a single tube assay that permits the recognition of mutant allele without suppression by wildtype signal. • Tumorplex™ provides a high level of sensitivity. • Tumorplex™ can be used with small sample size with mixed population of cells carrying heterogeneous gDNA. PMID:26258049
Ozone-Sensitive Arabidopsis Mutants with Deficiencies in Photorespiratory Enzymes.
Saji, Shoko; Bathula, Srinivas; Kubo, Akihiro; Tamaoki, Masanori; Aono, Mitsuko; Sano, Tomoharu; Tobe, Kazuo; Timm, Stefan; Bauwe, Hermann; Nakajima, Nobuyoshi; Saji, Hikaru
2017-05-01
An ozone-sensitive mutant was isolated from T-DNA-tagged lines of Arabidopsis thaliana. The T-DNA was inserted at a locus on chromosome 3, where two genes encoding glycolate oxidases, GOX1 and GOX2, peroxisomal enzymes involved in photorespiration, reside contiguously. The amounts of the mutant's foliar transcripts for these genes were reduced, and glycolate oxidase activity was approximately 60% of that of the wild-type plants. No difference in growth and appearance was observed between the mutant and the wild-type plants under normal conditions with ambient air under a light intensity of 100 µmol photons m-2 s-1. However, signs of severe damage, such as chlorosis and ion leakage from the tissue, rapidly appeared in mutant leaves in response to ozone treatment at a concentration of 0.2 µl l-1 under a higher light intensity of 350 µmol photons m-2 s-1 that caused no such symptoms in the wild-type plant. The mutant also exhibited sensitivity to sulfur dioxide and long-term high-intensity light. Arabidopsis mutants with deficiencies in other photorespiratory enzymes such as glutamate:glyoxylate aminotransferase and hydroxypyruvate reductase also exhibited ozone sensitivities. Therefore, photorespiration appears to be involved in protection against photooxidative stress caused by ozone and other abiotic factors under high-intensity light. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Genetic Map of Bacteriophage α
Kejzlarovà, J.; Donini, P.; Eremenko-Volpe, T.; Graziosi, F.
1970-01-01
Temperature-sensitive mutants of phage α were obtained by means of various mutagens and assigned to 25 complementation groups. Temperature-sensitive mutants belonging to 21 complementation groups and a mutant giving turbid plaques were used to perform two- and three-factor crosses. Seventeen of the cistrons and the turbid mutant were shown to belong to the same linear linkage group, which showed no signs of circularity. The remaining four unlinked cistrons showed peculiarities in their recombination properties. Genes which are known to be expressed earlier apear to be grouped together in a terminal segment of the linkage group. PMID:4990532
NASA Astrophysics Data System (ADS)
Chen, J. L.; Li, J.; Song, R.; Bai, L. L.; Shao, J. Z.; Qu, C. C.
2015-09-01
Laser cladding composite coatings were fabricated on the surface of the Ti6Al4V substrate by fiber laser cladding the NiCrBSi alloy powder. The influences of scanning speed on the dilution rate and microstructure of the coatings were investigated in detail by X-ray diffraction (XRD), optical microscopy (OM) and scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS). Combined with the analyses of microhardness and fracture toughness, the wear behaviors of the coatings obtained at different scanning speeds were revealed. Results indicated that the dilution rates of the coatings were similar (about 64.23%) with variations in scanning speed ranging from 5 mm/s to 15 mm/s. An abrupt decrease in dilution rate (37.06%) was observed at the scanning speed of 20 mm/s. Microstructural observation showed that the blocky TiB2 and the cellular dendrite TiC particles were uniformly dispersed in the TiNi-Ti2Ni dual-phase intermetallic compound matrix at scanning speeds of 5-15 mm/s. When the scanning speed was further increased to 20 mm/s, the stripe-shaped CrB, gray irregular-shaped Cr3C2 and black blocky TiC particles uniformly dispersed in the γ(Ni) matrix were synthesized in situ. The particles became finer with the increase in scanning speed. The average microhardness of the coating (1026.5 HV0.2) at the scanning speed of 20 mm/s was enhanced significantly compared with that of the other three coatings (about 886.4 HV0.2). The lowest average friction coefficient (about 0.371) was obtained at the scanning speed of 20 mm/s and was relatively stable with the change in sliding time. The lowest wear loss of the coating was also obtained at the scanning speed of 20 mm/s. Analyses of the worn surfaces showed that the coating prepared at the scanning speed of 20 mm/s was in good condition because of its excellent combination of resistance to micro-cutting and brittle debonding. Comparatively speaking, the coating produced at the scanning speed of 20 mm/s possessed excellent comprehensive mechanical properties.
Duan, Yuwei; Zhang, Baomei; Chu, Lianjun; Tong, Henry Hy; Liu, Weidong; Zhai, Guangxi
2016-05-01
The aim of this work is to prepare and characterize curcumin-loaded methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelles (CUR-MPP-TPGS-MMs), analyze the influence of formulation on enhancing the solubility of curcumin in water, and evaluate the improvement of intestinal absorption after oral administration. CUR-MPP-TPGS-MMs were prepared using the thin film diffusion method and optimized with the uniform design. The optimal CUR-MPP-TPGS-MMs were provided with high drug-loading (16.1%), small size (46.0 nm) and spherical shape. Low critical micelle concentration (CMC) and superior dilution stability showed that CUR-MPP-TPGS-MMs could keep integrity during the dilution of gastrointestinal fluid. In vitro drug release study indicated a sustained release of curcumin from CUR-MPP-TPGS-MMs in simulated gastrointestinal solution. The absorption mechanism of passive diffusion was obtained by measuring in situ intestinal absorption of CUR-MPP-TPGS-MMs in rats, and the best absorption segment was found to be the duodenum. The pharmacokinetics was evaluated in rats at the dose of 75 mg/kg by intragastric administration. The Cmax and mean retention time (MRT0-24) for CUR-MPP-TPGS-MMs were both increased, and the relative bioavailability of micelle formulation to curcumin suspension was 927.3%. These results suggested that mPEG-PLA/TPGS mixed micelle system (MPP-TPGS-MMs) showed great potential in improving oral bioavailability of curcumin. Copyright © 2016 Elsevier B.V. All rights reserved.
Maragh, Sherry L H; Brown, Marc D
2008-08-01
Antibiotics may be indiscriminately given to patients undergoing Mohs micrographic surgery (MMS) for the prevention of surgical site infections, despite a low risk of infection in these patients. We sought to evaluate the rate of wound infections among patients undergoing MMS without the use of prophylactic antibiotics. We prospectively evaluated 1000 consecutive patients undergoing MMS for nonmelanoma skin cancer or modified MMS/"slow Mohs" for lentigo maligna melanoma in situ. The overall wound infection rate among 1000 patients with 1115 tumors was 0.7% (8/1115 tumors). Five (62.5%) of 8 infections occurred on the nose with an overall 1.7% (5/302) nose infection rate. Seven (87.5%) of 8 infections occurred after flap reconstruction with an overall 2.4% (7/296) flap closure infection rate. Four (50%) of 8 infections occurred in patients requiring more than one Mohs stage for tumor clearance with a 0.8% (4/487) overall infection rate in cases requiring multiple Mohs stages. Two (25%) of 8 infections had cultures positive for oxacillin-resistant Staphylococcus aureus. No wound infections occurred in cases involving the lips or ears, skin-graft closures, or below-knee or modified MMS procedures. This was a prospective single institution uncontrolled study. Rates of infections among patients undergoing MMS or modified MMS are exceedingly low. Indiscriminate use of antibiotics increases patient risk to adverse drug reactions and antibiotic resistance. Administration of antibiotics to patients undergoing MMS should be on a case-by-case basis according to the known risk factors combined with clinical judgment.
HLA Amino Acid Polymorphisms and Kidney Allograft Survival
Kamoun, Malek; McCullough, Keith P.; Maiers, Martin; Fernandez Vina, Marcelo A.; Li, Hongzhe; Teal, Valerie; Leichtman, Alan B.; Merion, Robert M.
2017-01-01
Background The association of HLA mismatching with kidney allograft survival has been well established. We examined whether amino acid (AA) mismatches (MMs) at the antigen recognition site of HLA molecules represent independent and incremental risk factors for kidney graft failure (GF) beyond those MMs assessed at the antigenic (2-digit) specificity. Methods Data on 240 024 kidney transplants performed between 1987 and 2009 were obtained from the Scientific Registry of Transplant Recipients. We imputed HLA-A, -B, and -DRB1 alleles and corresponding AA polymorphisms from antigenic specificity through the application of statistical and population genetics inferences. GF risk was evaluated using Cox proportional-hazards regression models adjusted for covariates including patient and donor risk factors and HLA antigen MMs. Results We show that estimated AA MMs at particular positions in the peptide-binding pockets of HLA-DRB1 molecule account for a significant incremental risk that was independent of the well-known association of HLA antigen MMs with graft survival. A statistically significant linear relationship between the estimated number of AA MMs and risk of GF was observed for HLA-DRB1 in deceased donor and living donor transplants. This relationship was strongest during the first 12 months after transplantation (hazard ratio, 1.30 per 15 DRB1 AA MM; P < 0.0001). Conclusions This study shows that independent of the well-known association of HLA antigen (2-digit specificity) MMs with kidney graft survival, estimated AA MMs at peptide-binding sites of the HLA-DRB1 molecule account for an important incremental risk of GF. PMID:28221244
Devic, Eric; Li, Dunhai; Dauta, Alain; Henriksen, Peter; Codd, Geoffrey A.; Marty, Jean-Louis; Fournier, Didier
2002-01-01
Bioassays are little used to detect individual toxins in the environment because, compared to analytical methods, these assays are still limited by several problems, such as the sensitivity and specificity of detection. We tentatively solved these two drawbacks for detection of anatoxin-a(s) by engineering an acetylcholinesterase to increase its sensitivity and by using a combination of mutants to obtain increased analyte specificity. Anatoxin-a(s), a neurotoxin produced by some freshwater cyanobacteria, was detected by measuring the inhibition of acetylcholinesterase activity. By using mutated enzyme, the sensitivity of detection was brought to below the nanomole-per-liter level. However, anatoxin-a(s) is an organophosphorous compound, as are several synthetic molecules which are widely used as insecticides. The mode of action of these compounds is via inhibition of acetylcholinesterase, which makes the biotest nonspecific. The use of a four-mutant set of acetylcholinesterase variants, two mutants that are sensitive to anatoxin-a(s) and two mutants that are sensitive to the insecticides, allows specific detection of the cyanobacterial neurotoxin. PMID:12147513
ChR2 mutants at L132 and T159 with improved operational light sensitivity for vision restoration.
Pan, Zhuo-Hua; Ganjawala, Tushar H; Lu, Qi; Ivanova, Elena; Zhang, Zhifei
2014-01-01
The ectopic expression of microbial opsin-based optogenetic sensors, such as channelrhodopsin-2 (ChR2) in surviving inner retinal neurons, is a promising approach to restoring vision after retinal degeneration. However, a major limitation in using native ChR2 as a light sensor for vision restoration is the low light sensitivity of its expressing cells. Recently, two ChR2 mutations, T159C and L132C, were reported to produce higher photocurrents or have ultra light sensitivity. In this study, we created additional ChR2 mutants at these two sites to search for more light responsive ChR2 forms and evaluate their suitability for vision restoration by examining their light responsive properties in HEK cells and mouse retinal ganglion cells. We found additional ChR2 mutants at these two sites that showed a further increase in current amplitude at low light levels in the cells expressing these mutants, or operational light sensitivity. However, the increase in the operational light sensitivity was correlated with a decrease in temporal kinetics. Therefore, there is a trade-off between operational light sensitivity and temporal resolution for these more light responsive ChR2 mutants. Our results showed that for the two most light responsive mutants, L132C/T159C and L132C/T159S, the required light intensities for generating the threshold spiking activity in retinal ganglion cells were 1.5 and nearly 2 log units lower than wild-type ChR2 (wt-ChR2), respectively. Additionally, their ChR2-mediated spiking activities could follow flicker frequencies up to 20 and 10 Hz, respectively, at light intensities up to 1.5 log units above their threshold levels. Thus, the use of these more light responsive ChR2 mutants could make the optogenetic approach to restoring vision more feasible.
Crimella, Claudia; Cantoni, Orazio; Guidarelli, Andrea; Vantaggiato, Chiara; Martinuzzi, Andrea; Fiorani, Mara; Azzolini, Catia; Orso, Genny; Bresolin, Nereo; Bassi, Maria Teresa
2011-04-01
APTX is the gene involved in ataxia with oculomotor apraxia type 1 (AOA1), a recessive disorder with early-onset cerebellar ataxia, oculomotor apraxia and peripheral neuropathy. The encoded protein, aprataxin, is a DNA repair protein processing the products of abortive ligations, 5'-adenylated DNA. We describe a novel nonsense mutation in APTX, c.892C>T (p.Gln298X), segregating in two AOA1 patients and leading to the loss of aprataxin protein in patient's cells. These cells, while exhibiting reduced catalase activity, are not hypersensitive to toxicity elicited by H(2)O(2) exposure at either physiologic or ice-bath temperature. On the other hand, the rate of repair of DNA single-strand-breaks (SSBs) induced in both conditions is always significantly slower in AOA1 cells. By using the alkylating agent methyl methane sulphonate (MMS) we confirmed the association of the APTX mutation with a DNA repair defect in the absence of detectable changes in susceptibility to toxicity. These results, while consistent with a role of aprataxin in the repair of SSBs induced by H(2)O(2), or MMS, demonstrate that other mechanisms may be recruited in AOA1 cells to complete the repair process, although at a slower rate. Lack of hypersensitivity to the oxidant, or MMS, also implies that delayed repair is not per se a lethal event. © 2011 Wiley-Liss, Inc.
Magnetospheric Multiscale (MMS) Mission Commissioning Phase Orbit Determination Error Analysis
NASA Technical Reports Server (NTRS)
Chung, Lauren R.; Novak, Stefan; Long, Anne; Gramling, Cheryl
2009-01-01
The Magnetospheric MultiScale (MMS) mission commissioning phase starts in a 185 km altitude x 12 Earth radii (RE) injection orbit and lasts until the Phase 1 mission orbits and orientation to the Earth-Sun li ne are achieved. During a limited time period in the early part of co mmissioning, five maneuvers are performed to raise the perigee radius to 1.2 R E, with a maneuver every other apogee. The current baseline is for the Goddard Space Flight Center Flight Dynamics Facility to p rovide MMS orbit determination support during the early commissioning phase using all available two-way range and Doppler tracking from bo th the Deep Space Network and Space Network. This paper summarizes th e results from a linear covariance analysis to determine the type and amount of tracking data required to accurately estimate the spacecraf t state, plan each perigee raising maneuver, and support thruster cal ibration during this phase. The primary focus of this study is the na vigation accuracy required to plan the first and the final perigee ra ising maneuvers. Absolute and relative position and velocity error hi stories are generated for all cases and summarized in terms of the ma ximum root-sum-square consider and measurement noise error contributi ons over the definitive and predictive arcs and at discrete times inc luding the maneuver planning and execution times. Details of the meth odology, orbital characteristics, maneuver timeline, error models, and error sensitivities are provided.
30 CFR 285.534 - When may MMS cancel my bond?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false When may MMS cancel my bond? 285.534 Section 285.534 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE RENEWABLE... Assurance Requirements Changes in Financial Assurance § 285.534 When may MMS cancel my bond? When your lease...
30 CFR 285.202 - What types of leases will MMS issue?
Code of Federal Regulations, 2010 CFR
2010-07-01
... RENEWABLE ENERGY ALTERNATE USES OF EXISTING FACILITIES ON THE OUTER CONTINENTAL SHELF Issuance of OCS Renewable Energy Leases General Lease Information § 285.202 What types of leases will MMS issue? The MMS may issue leases on the OCS for the assessment and production of renewable energy and may authorize a...
30 CFR 280.73 - Will MMS share data and information with coastal States?
Code of Federal Regulations, 2010 CFR
2010-07-01
... Data Requirements Protections § 280.73 Will MMS share data and information with coastal States? (a) We... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Will MMS share data and information with coastal States? 280.73 Section 280.73 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE...
30 CFR 280.31 - Whom will MMS notify about environmental issues?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Whom will MMS notify about environmental issues... Obligations Under This Part Environmental Issues § 280.31 Whom will MMS notify about environmental issues? (a... submission for approval. (b) In cases where an environmental assessment is to be prepared, the Director will...
30 CFR 250.268 - How does MMS respond to recommendations?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false How does MMS respond to recommendations? 250.268 Section 250.268 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE... Decision Process for the Dpp Or Docd § 250.268 How does MMS respond to recommendations? (a) Governor. The...
30 CFR 250.920 - What are the MMS requirements for assessment of fixed platforms?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What are the MMS requirements for assessment of fixed platforms? 250.920 Section 250.920 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF... Structures Inspection, Maintenance, and Assessment of Platforms § 250.920 What are the MMS requirements for...
30 CFR 285.628 - How will MMS process my COP?
Code of Federal Regulations, 2010 CFR
2010-07-01
... allow this to occur. (g) If MMS approves your project easement, MMS will issue an addendum to your lease specifying the terms of the project easement. A project easement may include off-lease areas that: (1... feet (61 meters) in width, unless safety and environmental factors during construction and maintenance...
30 CFR 243.202 - When will MMS monitor my financial solvency?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false When will MMS monitor my financial solvency? 243.202 Section 243.202 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT SUSPENSIONS PENDING APPEAL AND BONDING-MINERALS REVENUE MANAGEMENT Financial Solvency Requirements § 243.202 When will MMS...
30 CFR 227.102 - What royalty management functions will MMS not delegate?
Code of Federal Regulations, 2010 CFR
2010-07-01
... payments shown on royalty reports or other documents, such as bills, to reconcile payor accounts. MMS also... actions other than issuing demands, subpoenas and orders to perform restructured accounting. MMS or the appropriate Federal agency will issue notices of non-compliance and civil penalties, collect debts, write off...
30 CFR 250.119 - Will MMS approve subsurface gas storage?
Code of Federal Regulations, 2010 CFR
2010-07-01
... of gas on the OCS, on and off-lease, for later commercial benefit. To receive MMS approval you must... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Will MMS approve subsurface gas storage? 250... OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF General Performance Standards § 250...
25 CFR 211.6 - Authority and responsibility of the Minerals Management Service (MMS).
Code of Federal Regulations, 2012 CFR
2012-04-01
... 25 Indians 1 2012-04-01 2011-04-01 true Authority and responsibility of the Minerals Management... MINERALS LEASING OF TRIBAL LANDS FOR MINERAL DEVELOPMENT General § 211.6 Authority and responsibility of the Minerals Management Service (MMS). The functions of the MMS for reporting, accounting, and...
25 CFR 212.6 - Authority and responsibility of the Minerals Management Service (MMS).
Code of Federal Regulations, 2010 CFR
2010-04-01
... 25 Indians 1 2010-04-01 2010-04-01 false Authority and responsibility of the Minerals Management... MINERALS LEASING OF ALLOTTED LANDS FOR MINERAL DEVELOPMENT General § 212.6 Authority and responsibility of the Minerals Management Service (MMS). The functions of the MMS for reporting, accounting, and...
25 CFR 225.6 - Authority and responsibility of the Minerals Management Service (MMS).
Code of Federal Regulations, 2014 CFR
2014-04-01
... 25 Indians 1 2014-04-01 2014-04-01 false Authority and responsibility of the Minerals Management... MINERALS OIL AND GAS, GEOTHERMAL, AND SOLID MINERALS AGREEMENTS General § 225.6 Authority and responsibility of the Minerals Management Service (MMS). The functions of the MMS for reporting, accounting, and...
25 CFR 211.6 - Authority and responsibility of the Minerals Management Service (MMS).
Code of Federal Regulations, 2011 CFR
2011-04-01
... 25 Indians 1 2011-04-01 2011-04-01 false Authority and responsibility of the Minerals Management... MINERALS LEASING OF TRIBAL LANDS FOR MINERAL DEVELOPMENT General § 211.6 Authority and responsibility of the Minerals Management Service (MMS). The functions of the MMS for reporting, accounting, and...
25 CFR 225.6 - Authority and responsibility of the Minerals Management Service (MMS).
Code of Federal Regulations, 2012 CFR
2012-04-01
... 25 Indians 1 2012-04-01 2011-04-01 true Authority and responsibility of the Minerals Management... MINERALS OIL AND GAS, GEOTHERMAL, AND SOLID MINERALS AGREEMENTS General § 225.6 Authority and responsibility of the Minerals Management Service (MMS). The functions of the MMS for reporting, accounting, and...
25 CFR 212.6 - Authority and responsibility of the Minerals Management Service (MMS).
Code of Federal Regulations, 2012 CFR
2012-04-01
... 25 Indians 1 2012-04-01 2011-04-01 true Authority and responsibility of the Minerals Management... MINERALS LEASING OF ALLOTTED LANDS FOR MINERAL DEVELOPMENT General § 212.6 Authority and responsibility of the Minerals Management Service (MMS). The functions of the MMS for reporting, accounting, and...
25 CFR 211.6 - Authority and responsibility of the Minerals Management Service (MMS).
Code of Federal Regulations, 2010 CFR
2010-04-01
... 25 Indians 1 2010-04-01 2010-04-01 false Authority and responsibility of the Minerals Management... MINERALS LEASING OF TRIBAL LANDS FOR MINERAL DEVELOPMENT General § 211.6 Authority and responsibility of the Minerals Management Service (MMS). The functions of the MMS for reporting, accounting, and...
Smc5/6-Mms21 Prevents and Eliminates Inappropriate Recombination Intermediates in Meiosis
Xaver, Martin; Huang, Lingzhi; Chen, Doris; Klein, Franz
2013-01-01
Repairing broken chromosomes via joint molecule (JM) intermediates is hazardous and therefore strictly controlled in most organisms. Also in budding yeast meiosis, where production of enough crossovers via JMs is imperative, only a subset of DNA breaks are repaired via JMs, closely regulated by the ZMM pathway. The other breaks are repaired to non-crossovers, avoiding JM formation, through pathways that require the BLM/Sgs1 helicase. “Rogue” JMs that escape the ZMM pathway and BLM/Sgs1 are eliminated before metaphase by resolvases like Mus81-Mms4 to prevent chromosome nondisjunction. Here, we report the requirement of Smc5/6-Mms21 for antagonizing rogue JMs via two mechanisms; destabilizing early intermediates and resolving JMs. Elimination of the Mms21 SUMO E3-ligase domain leads to transient JM accumulation, depending on Mus81-Mms4 for resolution. Absence of Smc6 leads to persistent rogue JMs accumulation, preventing chromatin separation. We propose that the Smc5/6-Mms21 complex antagonizes toxic JMs by coordinating helicases and resolvases at D-Loops and HJs, respectively. PMID:24385936
GPS Navigation Above 76,000 km for the MMS Mission
NASA Technical Reports Server (NTRS)
Winternitz, Luke; Bamford, Bill; Price, Samuel; Long, Anne; Farahmand, Mitra; Carpenter, Russell
2016-01-01
NASA's MMS mission, launched in March of 2015,consists of a controlled formation of four spin-stabilized spacecraft in similar highly elliptic orbits reaching apogee at radial distances of 12and 25 Earth radii in the first and second phases of the mission. Navigation for MMS is achieved independently onboard each spacecraft by processing GPS observables using NASA GSFC's Navigator GPS receiver and the Goddard Enhanced Onboard Navigation System (GEONS) extended Kalman filter software. To our knowledge, MMS constitutes, by far, the highest-altitude operational use of GPS to date and represents the culmination of over a decade of high-altitude GPS navigation research and development at NASA GSFC. In this paper we will briefly describe past and ongoing high-altitude GPS research efforts at NASA GSFC and elsewhere, provide details on the design of the MMS GPS navigation system, and present on-orbit performance data. We extrapolate these results to predict performance in the Phase 2b mission orbit, and conclude with a discussion of the implications of the MMS results for future high-altitude GPS navigation, which we believe to be broad and far-reaching.
Isolation and Characterization of Sex-Linked Female-Sterile Mutants in DROSOPHILA MELANOGASTER
Gans, Madeleine; Audit, Claudie; Masson, Michele
1975-01-01
The purpose of the experiments described was to identify X chromosome genes functioning mainly or exclusively during oogenesis. Two mutagenesis experiments were carried out with ethyl methane sulfonate. Following treatment inducing 60% lethals, 9% of the treated X chromosomes carried a female sterility mutation which did not otherwise seriously affect viability. Among —95 isolated mutants, 19 were heat-sensitive and 5 cold-sensitive. The mutants have been classified as follows: I (16 mutants; 12 complementation groups): the females laid few or no eggs; the defect concerned either ovulation or oogenesis. II (37 mutants; 18 complementation groups): the female laid morphologically abnormal eggs, often with increased membrane permeability. III A (13 mutants; at least 8 complementation groups): the homozygous females were sterile if mated to mutant males; their progeny (homo- and hemizygous) died at a late embryonic stage (11 mutants), at the larval stage (1 mutant) or at the pupal stage (1 mutant). However fertility was partly restored by breeding to wild-type males as shown by survival of some heterozygous descendants. III B (29 mutants; 22 complementation groups): the fertility of the females was not restored by breeding to a wild-type male. Most of the eggs of 13 of the mutants died at a late stage of embryogenesis. The eggs of the others ceased development earlier or, perhaps, remained unfertilized. The distribution of the number of mutants per complementation group led to an estimation of a total of about 150 X-linked genes involved in female fertility. The females of three mutants, heat-sensitive and totally sterile at 29°, produced at a lower temperature descendants morphologically abnormal or deprived of germ cells. Three other mutants not described in detail showed a reduction in female fertility with many descendants lacking germ cells. A desirable mutant which was not recovered was one with normal fertile females producing descendants which, regardless of their genotype, bore specific morphological abnormalities. The value of the mutants isolated for analysis of the complex processes leading to egg formation and initiation of development is discussed. PMID:814037
Deletion of HAPS_2096 Increases Sensitivity to Cecropin B in Haemophilus parasuis.
Chen, Fanjie; Hu, Han; Li, Zhonghua; Huang, Jiacheng; Cai, Xuwang; Wang, Chunmei; He, Qigai; Cao, Jiyue
2015-01-01
Cecropin B (CB) is a very effective natural antimicrobial peptide that has shown great potential for future antimicrobial drug development. HAPS_2096 is a Haemophilus parasuis gene that encodes the periplasmic substrate-binding protein of an ATP-binding cassette-type amino acid transporter. In this research, we constructed and verified an HAPS_2096 deletion mutant and a complementary HAPS_2096 mutant of H. parasuis JS0135. A bactericidal assay revealed that the HAPS_2096 deletion mutant was significantly more sensitive than the wild-type strain to 0.25-0.5 µg/ml CB. However, the gene complementation alleviated the CB sensitivity of the mutant. Immunoelectron microscopy observation following a 30-min treatment with a sublethal concentration of CB (0.25 μg/ml) revealed more extensive morphological damage in the mutant strain than in the wild-type strain. Hence, our results suggest that the HAPS_2096 gene contributes to H. parasuis resistance to CB. © 2015 S. Karger AG, Basel.
2014-10-29
CAPE CANAVERAL, Fla. – A crane is lowered toward the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, during uncrating operations in the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-10-29
CAPE CANAVERAL, Fla. – Workers position two of the observatories, the lower stack, mini-stack number 1 for NASA's Magnetospheric Multiscale Observatory, or MMS, onto a payload dolly in the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-10-29
CAPE CANAVERAL, Fla. – Workers prepare a payload dolly for the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, during uncrating operations in the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-10-30
CAPE CANAVERAL, Fla. – Technicians begin to remove the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-10-30
CAPE CANAVERAL, Fla. – Preparations are underway to remove the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-10-30
CAPE CANAVERAL, Fla. – Technicians have removed most of the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-11-13
CAPE CANAVERAL, Fla. – The Magnetospheric Multiscale, or MMS, spacecraft will undergo final processing for launch now that all four are in the Building 1 high bay of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the upper deck arrived Nov. 12; the two MMS spacecraft comprising the lower stack arrived Oct. 29. The Magnetospheric Multiscale mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-10-29
CAPE CANAVERAL, Fla. – Two of the observatories, the lower stack, mini-stack number 1, for NASA's Magnetospheric Multiscale Observatory, or MMS, glides toward a payload dolly during uncrating operations in the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-10-30
CAPE CANAVERAL, Fla. – Technicians prepare to remove the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-11-14
CAPE CANAVERAL, Fla. – Workers inspect the solar arrays on the Magnetospheric Multiscale, or MMS, observatories in the Building 1 D high bay of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the upper deck arrived Nov. 12; the two comprising the lower stack arrived Oct. 29. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-11-14
CAPE CANAVERAL, Fla. – Workers inspect the solar arrays on the Magnetospheric Multiscale, or MMS, observatories in the Building 1 D high bay of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the upper deck arrived Nov. 12; the two comprising the lower stack arrived Oct. 29. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-10-29
CAPE CANAVERAL, Fla. – Preparations are underway to remove the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, from their protective shipping container in the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-10-29
CAPE CANAVERAL, Fla. – The protective shipping container is lifted from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-11-14
CAPE CANAVERAL, Fla. – Workers inspect the solar arrays on the Magnetospheric Multiscale, or MMS, observatories in the Building 1 D high bay of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the upper deck arrived Nov. 12; the two comprising the lower stack arrived Oct. 29. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-10-30
CAPE CANAVERAL, Fla. – Most of the protective covering has been removed from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, inside Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
Magnetospheric Multiscale (MMS)
2014-05-09
Electrical technicians work diligently to build the connector harnessing for the Command and Data Handling (C&DH) unit, (black box with two red handles) that is installed on spacecraft Deck for MMS #4. Learn more about MMS at www.nasa.gov/mms Credit NASA/Goddard The Magnetospheric Multiscale, or MMS, will study how the sun and the Earth's magnetic fields connect and disconnect, an explosive process that can accelerate particles through space to nearly the speed of light. This process is called magnetic reconnection and can occur throughout all space. 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
2014-10-30
CAPE CANAVERAL, Fla. – Technicians begin to remove the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-10-30
CAPE CANAVERAL, Fla. – A technician prepares to remove the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-10-30
CAPE CANAVERAL, Fla. – Technicians remove the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-11-14
CAPE CANAVERAL, Fla. – Workers inspect the solar arrays on the Magnetospheric Multiscale, or MMS, observatories in the Building 1 D high bay of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the upper deck arrived Nov. 12; the two comprising the lower stack arrived Oct. 29. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-10-29
CAPE CANAVERAL, Fla. – Preparations are underway to tow two of the observatories, the lower stack, mini-stack number 1, for NASA's Magnetospheric Multiscale Observatory, or MMS, from the Building 2 south encapsulation bay to the Building 1 high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-11-14
CAPE CANAVERAL, Fla. – Workers inspect the solar arrays on the Magnetospheric Multiscale, or MMS, observatories in the Building 1 D high bay of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the upper deck arrived Nov. 12; the two comprising the lower stack arrived Oct. 29. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-10-30
CAPE CANAVERAL, Fla. – Most of the protective covering has been removed from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, inside Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-10-30
CAPE CANAVERAL, Fla. – Technicians remove the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-11-14
CAPE CANAVERAL, Fla. – Workers inspect the solar arrays on the Magnetospheric Multiscale, or MMS, observatories in the Building 1 D high bay of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the upper deck arrived Nov. 12; the two comprising the lower stack arrived Oct. 29. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-10-30
CAPE CANAVERAL, Fla. – Technicians remove the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-10-30
CAPE CANAVERAL, Fla. – A technician carefully removes the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
2014-11-14
CAPE CANAVERAL, Fla. – Workers inspect the solar arrays on the Magnetospheric Multiscale, or MMS, observatories in the Building 1 D high bay of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the upper deck arrived Nov. 12; the two comprising the lower stack arrived Oct. 29. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
Goalpha regulates volatile anesthetic action in Caenorhabditis elegans.
van Swinderen, B; Metz, L B; Shebester, L D; Mendel, J E; Sternberg, P W; Crowder, C M
2001-01-01
To identify genes controlling volatile anesthetic (VA) action, we have screened through existing Caenorhabditis elegans mutants and found that strains with a reduction in Go signaling are VA resistant. Loss-of-function mutants of the gene goa-1, which codes for the alpha-subunit of Go, have EC(50)s for the VA isoflurane of 1.7- to 2.4-fold that of wild type. Strains overexpressing egl-10, which codes for an RGS protein negatively regulating goa-1, are also isoflurane resistant. However, sensitivity to halothane, a structurally distinct VA, is differentially affected by Go pathway mutants. The RGS overexpressing strains, a goa-1 missense mutant found to carry a novel mutation near the GTP-binding domain, and eat-16(rf) mutants, which suppress goa-1(gf) mutations, are all halothane resistant; goa-1(null) mutants have wild-type sensitivities. Double mutant strains carrying mutations in both goa-1 and unc-64, which codes for a neuronal syntaxin previously found to regulate VA sensitivity, show that the syntaxin mutant phenotypes depend in part on goa-1 expression. Pharmacological assays using the cholinesterase inhibitor aldicarb suggest that VAs and GOA-1 similarly downregulate cholinergic neurotransmitter release in C. elegans. Thus, the mechanism of action of VAs in C. elegans is regulated by Goalpha, and presynaptic Goalpha-effectors are candidate VA molecular targets. PMID:11404329
Luo, Chong; Cao, Chunlei; Jiang, Linghuo
2016-05-01
Nickel is one of the toxic environment metal pollutants and is linked to various human diseases. In this study, through a functional genomics approach we have identified 16 nickel-sensitive and 22 nickel-tolerant diploid deletion mutants of budding yeast genes, many of which are novel players in the regulation of nickel homeostasis. The 16 nickel-sensitive mutants are of genes mainly involved in the protein folding, modification and destination and the cellular transport processes, while the 22 nickel-tolerant mutants are of genes encoding components of ESCRT complexes as well as protein factors involved in both the cell wall integrity maintenance and the vacuolar protein sorting process. In consistence with their phenotypes, most of these nickel-sensitive mutants show reduced intracellular nickel contents, while the majority of these nickel-tolerant mutants show elevated intracellular nickel contents, as compared to the wild type in response to nickel stress. Our data provides a basis for our understanding the regulation of nickel homeostasis and molecular mechanisms of nickel-induced human pathogenesis. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Sloothaak, D A M; van der Linden, R L A; van de Velde, C J H; Bemelman, W A; Lips, D J; van der Linden, J C; Doornewaard, H; Tanis, P J; Bosscha, K; van der Zaag, E S; Buskens, C J
2017-08-01
Occult nodal tumour cells should be categorised as micrometastasis (MMs) and isolated tumour cells (ITCs). A recent meta-analysis demonstrated that MMs, but not ITCs, are prognostic for disease recurrence in patients with stage I/II colon cancer. The objective of this retrospective multicenter study was to correlate MMs and ITCs to characteristics of the primary tumour, and to determine their prognostic value in patients with stage I/II colon cancer. One hundred ninety two patients were included in the study with a median follow up of 46 month (IQR 33-81 months). MMs were found in eight patients (4.2%), ITCs in 37 (19.3%) and occult tumour cells were absent in 147 patients (76.6%). Between these groups, tumour differentiation and venous or lymphatic invasion was equally distributed. Advanced stage (pT3/pT4) was found in 66.0% of patients without occult tumour cells (97/147), 72.9% of patients with ITCs (27/37), and 100% in patients with MMs (8/8), although this was a non-significant trend. Patients with MMs showed a significantly reduced 3 year-disease free survival compared to patients with ITCs or patients without occult tumour cells (75.0% versus 88.0% and 94.8%, respectively, p = 0.005). When adjusted for T-stage, MMs independently predicted recurrence of cancer (OR 7.6 95% CI 1.5-37.4, p = 0.012). In this study, the incidence of MMs and ITCs in patients with stage I/II colon cancer was 4.2% and 19.3%, respectively. MMs were associated with an reduced 3 year disease free survival rate, but ITCs were not. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
Access and Use of MMS Data through SPDF Services
NASA Astrophysics Data System (ADS)
McGuire, R. E.; Bilitza, D.; Boardsen, S. A.; Candey, R. M.; Chimiak, R.; Cooper, J. F.; Garcia, L. N.; Harris, B. T.; Johnson, R. C.; Kovalick, T. J.; Lal, N.; Leckner, H. A.; Liu, M. H.; Papitashvili, N. E.; Rao, U. R.; Roberts, D. A.; Yurow, R. E.
2016-12-01
In its role as a Heliophysics Active Final Archive and in close cooperation with the MMS project and its Science Data Center, the Space Physics Data Facility (SPDF) now serves a full set of public MMS data and QuickLook plots. All SPDF services for this data and all data are available via links from the SPDF home page (http://spdf.gsfc.nasa.gov). SPDF's CDAWeb features MMS Level-2 survey and burst mode data with graphics, listing and data superset/subset functions. These capabilities are available (1) through our html user interface, (2) through calls to our CDAS web services API, and (3) through other interfaces and libraries using the CDAS web services or that otherwise access our holdings including SPDF's Heliophysics Data Portal and several external systems. As context in use of the MMS data, CDAWeb also serves current data from many other current missions. These include the Van Allen Probes 1/2 and the five THEMIS/ARTEMIS spacecraft, as well as e.g. ACE, Cluster 1/2/3/4, DMSP 16/17/18, Geotail, GOES 13/14/15, NOAA/POES 15/16/18/19, MetOP POES 1/2, Stereo A/B, TWINS 1/2, Wind and >120 Ground-Based investigations). This full set of public MMS Level-2 science data and QuickLook plots, and all other public data held by SPDF, are also available for direct file download by HTTP or FTP links from the SPDF home page above. As a reminder, MMS Level-2 data are publicly available about 30 days after data is taken, and QuickLook survey plots are available about a day after data is taken). MMS orbits (current and predictive) are served through SPDF's SSCWeb service and our Java-based interactive 4D Orbit Viewer, also with orbits of many other current missions). Our presentation will discuss recent enhancements to CDAWeb and other services and our plans to support new MMS data products and upcoming heliophysics missions including ICON, GOLD and Solar Probe Plus.
NASA Astrophysics Data System (ADS)
Noguchi, Takaaki; Ohashi, Noriaki; Tsujimoto, Shinichi; Mitsunari, Takuya; Bradley, John P.; Nakamura, Tomoki; Toh, Shoichi; Stephan, Thomas; Iwata, Naoyoshi; Imae, Naoya
2015-01-01
Chondritic porous interplanetary dust particles (CP IDPs) collected in the stratosphere are regarded as possibly being cometary dust, and are therefore the most primitive solar system material that is currently available for analysis in laboratories. In this paper we report the discovery of more than 40 chondritic porous micrometeorites (CP MMs) in the surface snow and blue ice of Antarctica, which are indistinguishable from CP IDPs. The CP MMs are botryoidal aggregates, composed mainly of sub-micrometer-sized constituents. They contain two components that characterize them as CP IDPs: enstatite whiskers and GEMS (glass with embedded metal and sulfides). Enstatite whiskers appear as <2-μm-long acicular objects that are attached on, or protrude from the surface, and when included in the interior of the CP MMs are composed of a unit-cell scale mixture of clino- and ortho-enstatite, and elongated along the [100] direction. GEMS appear as 100-500 nm spheroidal objects containing <50 nm Fe-Ni metal and Fe sulfide. The CP MMs also contain low-iron-manganese-enriched (LIME) and low-iron-chromium-enriched (LICE) ferromagnesian silicates, kosmochlor (NaCrSi2O6)-rich high-Ca pyroxene, roedderite (K, Na)2Mg5Si12O30, and carbonaceous nanoglobules. These components have previously been discovered in primitive solar system materials such as the CP IDPs, matrices of primitive chondrites, phyllosilicate-rich MMs, ultracarbonaceous MMs, and cometary particles recovered from the 81P/Wild 2 comet. The most outstanding feature of these CP MMs is the presence of kosmochlor-rich high-Ca pyroxene and roedderite, which suggest that they have building blocks in common with CP IDPs and cometary dust particles and therefore suggest a possible cometary origin of both CP MMs and CP IDPs. It is therefore considered that CP MMs are CP IDPs that have fallen to Earth and have survived the terrestrial environment.
Magnetospheric Multiscale Mission Navigation Performance During Apogee-Raising and Beyond
NASA Technical Reports Server (NTRS)
Farahmand, Mitra; Long, Anne; Hollister, Jacob; Rose, Julie; Godine, Dominic
2017-01-01
The primary objective of the Magnetospheric Multiscale (MMS) Mission is to study the magnetic reconnection phenomena in the Earths magnetosphere. The MMS mission consists of four identical spinning spacecraft with the science objectives requiring a tetrahedral formation in highly elliptical orbits. The MMS spacecraft are equipped with onboard orbit and time determination software, provided by a weak-signal Global Positioning System (GPS) Navigator receiver hosting the Goddard Enhanced Onboard Navigation System (GEONS). This paper presents the results of MMS navigation performance analysis during the Phase 2a apogee-raising campaign and Phase 2b science segment of the mission.
Characterization of the growth and auxin physiology of roots of the tomato mutant, diageotropica
NASA Technical Reports Server (NTRS)
Muday, G. K.; Lomax, T. L.; Rayle, D. L.
1995-01-01
Roots of the tomato (Lycopersicon esculentum, Mill.) mutant (diageotropica (dgt) exhibit an altered phenotype. These roots are agravitropic and lack lateral roots. Relative to wild-type (VFN8) roots, dgt roots are less sensitive to growth inhibition by exogenously applied IAA and auxin transport inhibitors (phytotropins), and the roots exhibit a reduction in maximal growth inhibition in response to ethylene. However, IAA transport through roots, binding of the phytotropin, tritiated naphthylphthalamic acid ([3H]NPA), to root microsomal membranes, NPA-sensitive IAA uptake by root segments, and uptake of [3H]NPA into root segments are all similar in mutant and wild-type roots. We speculate that the reduced sensitivity of dgt root growth to auxin-transport inhibitors and ethylene is an indirect result of the reduction in sensitivity to auxin in this single gene, recessive mutant. We conclude that dgt roots, like dgt shoots, exhibit abnormalities indicating they have a defect associated with or affecting a primary site of auxin perception or action.
Polarity-defective mutants of Aspergillus nidulans.
Osherov, N; Mathew, J; May, G S
2000-12-01
We have identified two polarity-defective (pod) mutants in Aspergillus nidulans from a collection of heat-sensitive lethal mutants. At restrictive temperature, these mutants are capable of nuclear division but are unable to establish polar hyphal growth. We cloned the two pod genes by complementation of their heat-sensitive lethal phenotypes. The libraries used to clone the pod genes are under the control of the bidirectional niaD and niiA promoters. Complementation of the pod mutants is dependent on growth on inducing medium. We show that rescue of the heat-sensitive phenotype on inducing media is independent of the orientation of the gene relative to the niaD or niiA promoters, demonstrating that the intergenic region between the niaD and the niiA genes functions as an orientation-independent enhancer and repressor that is capable of functioning over long distances. The products of the podG and the podH genes were identified as homologues of the alpha subunit of yeast mitochondrial phenylalanyl--tRNA synthetase and transcription factor IIF interacting component of the CTD phosphatase. Neither of these gene products would have been predicted to produce a pod mutant phenotype based on studies of cellular polarity mutants in other organisms. The implications of these results are discussed. Copyright 2000 Academic Press.
30 CFR 206.178 - How do I determine a transportation allowance?
Code of Federal Regulations, 2010 CFR
2010-07-01
... the end of the 12-month period to which the allowance applies. However, MMS may approve a longer time... Poor's Bond Guide for the first month of the reporting period for which the allowance is applicable and... months of the date MMS receives your report which claims the allowance on the Form MMS-2014. (ii) When...
30 CFR 285.636 - What notices must I provide MMS following approval of my COP?
Code of Federal Regulations, 2010 CFR
2010-07-01
... approval of my COP? 285.636 Section 285.636 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF... SHELF Plans and Information Requirements Activities Under An Approved Cop § 285.636 What notices must I provide MMS following approval of my COP? You must notify MMS in writing of the following events, within...
30 CFR 285.636 - What notices must I provide MMS following approval of my COP?
Code of Federal Regulations, 2011 CFR
2011-07-01
... approval of my COP? 285.636 Section 285.636 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION... FACILITIES ON THE OUTER CONTINENTAL SHELF Plans and Information Requirements Activities Under An Approved Cop § 285.636 What notices must I provide MMS following approval of my COP? You must notify MMS in writing...
30 CFR 250.231 - After receiving the EP, what will MMS do?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false After receiving the EP, what will MMS do? 250.231 Section 250.231 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE... Decision Process for the Ep § 250.231 After receiving the EP, what will MMS do? (a) Determine whether...
30 CFR 227.109 - What if the MMS Director denies a State's delegation proposal?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What if the MMS Director denies a State's delegation proposal? 227.109 Section 227.109 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT DELEGATION TO STATES Delegation Process § 227.109 What if the MMS...
30 CFR 250.231 - After receiving the EP, what will MMS do?
Code of Federal Regulations, 2011 CFR
2011-07-01
... 30 Mineral Resources 2 2011-07-01 2011-07-01 false After receiving the EP, what will MMS do? 250.231 Section 250.231 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND ENFORCEMENT... and Information Review and Decision Process for the Ep § 250.231 After receiving the EP, what will MMS...
30 CFR 227.108 - How will MMS notify a State of its decision?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false How will MMS notify a State of its decision? 227.108 Section 227.108 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT DELEGATION TO STATES Delegation Process § 227.108 How will MMS notify a State...
Exploring Factors Influencing Mobile Users' Intention to Adopt Multimedia Messaging Service
ERIC Educational Resources Information Center
Chang, Shuchih Ernest; Pan, Ying-Hui Vera
2011-01-01
While short messaging service (SMS) is discussed often in recent literature, multimedia messaging service (MMS), a media rich successor of SMS, is seldom heard or understood by mobile users in Taiwan. The adoption rates of MMS are far from satisfactory, implying that there might be some factors keeping the potential users away from using MMS. This…
30 CFR 241.77 - How may MMS collect the penalty?
Code of Federal Regulations, 2010 CFR
2010-07-01
... MMS collect the penalty? (a) MMS may use all available means to collect the penalty including, but not... to compel your payment under 30 U.S.C. 1719(k). (b) If the Department uses judicial process, or if you seek judicial review under § 241.74 and the court upholds assessment of a penalty, the court shall...
Magnetospheric Multiscale Mission Micrometeoroid/Orbital Debris Impacts
NASA Technical Reports Server (NTRS)
Williams, Trevor; Sedlak, Joseph; Shulman, Seth
2017-01-01
The MMS spacecraft are highly instrumented (accelerometers, star cameras, Sun sensors, science experiments for plasmas etc.). This presentation will discuss how data from these systems has allowed two micrometeoroid/orbital debris events to be studied: the Feb. 2, 2016 impact with an MMS4 shunt resistor, and the June 12, 2016 impact with an MMS4 wire boom.
30 CFR 227.101 - What royalty management functions may MMS delegate to a State?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What royalty management functions may MMS delegate to a State? 227.101 Section 227.101 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF... § 227.101 What royalty management functions may MMS delegate to a State? (a) If there are oil and gas...
30 CFR 227.104 - What will MMS do when it receives a State's delegation proposal?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What will MMS do when it receives a State's delegation proposal? 227.104 Section 227.104 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT DELEGATION TO STATES Delegation Proposals § 227.104 What will MMS do...
30 CFR 250.1508 - What must I do when MMS administers written or oral tests?
Code of Federal Regulations, 2010 CFR
2010-07-01
... oral tests? 250.1508 Section 250.1508 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Well Control and Production Safety Training § 250.1508 What must I do when MMS administers written or oral tests? MMS or its...
Wheat ABA-insensitive mutants result in reduced grain dormancy
USDA-ARS?s Scientific Manuscript database
This paper describes the isolation of wheat mutants in the hard red spring Scarlet resulting in reduced sensitivity to the plant hormone abscisic acid (ABA) during seed germination. ABA induces seed dormancy during embryo maturation and inhibits the germination of mature seeds. Wheat sensitivity t...
SPDF Data and Orbit Services Supporting Open Access, Use and Archiving of MMS Data
NASA Astrophysics Data System (ADS)
McGuire, R. E.; Bilitza, D.; Candey, R. M.; Chimiak, R.; Cooper, J. F.; Garcia, L. N.; Harris, B. T.; Johnson, R. C.; Kovalick, T. J.; Lal, N.; Leckner, H. A.; Liu, M. H.; Papitashvili, N. E.; Roberts, D. A.; Yurow, R. E.
2015-12-01
NASA's Space Physics Data Facility (SPDF) project is now serving MMS definitive and predictive interactive orbit plots, listings and conjunction calculations through our SSCWeb and 4D Orbit Viewer services. In March 2016 and in parallel with the MMS Science Data Center (SDC) at LASP, SPDF will begin publicly serving a complete set of MMS Level-2 and higher, survey and burst-mode science data products from all four spacecraft and all instruments. The initial Level-2 data available will be from September 2015 to early February 2016, with Level-2 products subsequently validated and publicly available with an approximate one month lag. All MMS Level-2 and higher data products are produced in standard CDF format with standard ISTP/SPDF metadata and will be served by SPDF through our CDAWeb data service, including our web services and associated APIs for IDL and Matlab users, and through direct FTP/HTTP directory browse and file downloads. SPDF's ingest, archival preservation and active serving of current MMS science data is part of our role as an active heliophysics final archive. SPDF's ingest of complete and current science data products from other active heliophysics missions with SPDF services will help enable coordinated and correlative MMS science analysis by the open international science community with current data from THEMIS, the Van Allen Probes and other missions including TWINS, Cluster, ACE, Wind, >120 ground magnetometer stations as well as instruments on the NOAA GOES and POES spacecraft. Please see the related Candey et.al. paper on "SPDF Ancillary Services and Technologies Supporting Open Access, Use and Archiving of MMS Data" for other aspects of what SPDF is doing. All SPDF data and services are available from the SPDF home page at http://spdf.gsfc.nasa.gov .
Jiang, Ying; Shan, Shigang; Chi, Linfeng; Zhang, Guanglin; Gao, Xiangjing; Li, Hongjuan; Zhu, Xinqiang; Yang, Jun
2016-03-01
Methyl methanesulfonate (MMS) is an alkylating agent that can induce cell death through apoptosis and necroptosis. The molecular mechanisms underlying MMS-induced apoptosis have been studied extensively; however, little is known about the mechanism for MMS-induced necroptosis. Therefore, we first established MMS-induced necroptosis model using human lung carcinoma A549 cells. It was found that, within a 24-h period, although MMS at concentrations of 50, 100, 200, 400, and 800 μM can induce DNA damage, only at higher concentrations (400 and 800 μM) MMS treatment lead to necroptosis in A549 cells, as it could be inhibited by the specific necroptotic inhibitor necrostatin-1, but not the specific apoptotic inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-fmk). MMS-induced necroptosis was further confirmed by the induction of the necroptosis biomarkers including the depletion of cellular NADH and ATP and leakage of LDH. This necroptotic cell death was also concurrent with the increased expression of p53, p53-induced gene 3 (PIG-3), high mobility group box-1 protein (HMGB1), and receptor interaction protein kinase (RIP) but not the apoptosis-associated caspase-3 and caspase-9 proteins. Elevated reactive oxygen species (ROS) level was also involved in this process as the specific ROS inhibitor (4-amino-2,4-pyrrolidine-dicarboxylic acid (APDC)) can inhibit the necroptotic cell death. Interestingly, knockdown of PIG-3 expression by small interfering RNA (siRNA) treatment can inhibit the generation of ROS. Taken together, these results suggest that MMS can induce necroptosis in A549 cells, probably through the PIG-3-ROS pathway.
A Literature Review on the Mechanism of Action of Sulphur and Nitrogen Mustard
1989-07-01
for years is also poeqible (Aasted et al, 1987; Colardyn et al, 1986). Severely poisoned individuals exhibit bone marrow depression and may die from...MMS does not produce the enhanced depression of DNA synthesis in sensitive cells, compared to resistant cells, produced by sulphur mustard and...Compound MATD 1 Protection (mg/mouse) index 2 WR-3689 15 159 WR-2721 15 44 Aminoethylcysteine 80 27 N- acetylcysteine 8 26 Glutathione 60 22 Cysteine 8
2014-08-04
NASA Administrator Charles Bolden listens to Magnetospheric Multiscale (MMS) Mission Project Manager Craig Tooley talk about the MMS mission outside of a Naval Research Laboratory cleanroom where one of four Magnetospheric Multiscale (MMS) spacecraft is currently undergoing testing, Monday, August 4, 2014, in Washington. The Magnetospheric Multiscale, or MMS, mission will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known as magnetic reconnection. The four identical spacecraft are scheduled to launch in 2015 from Cape Canaveral and will orbit around Earth in varying formations through the dynamic magnetic system surrounding our planet to provide the first three-dimensional views of the magnetic reconnection process. The goal of the STP Program is to understand the fundamental physical processes of the space environment from the sun to Earth, other planets, and the extremes of the solar system boundary. Photo Credit: (NASA/Bill Ingalls)
NASA Astrophysics Data System (ADS)
Myers, Rachel; Egedal, Jan; Olson, Joseph; Greess, Samuel; Millet-Ayala, Alexander; Clark, Michael; Nonn, Paul; Wallace, John; Forest, Cary
2017-10-01
The NASA Magnetospheric Multiscale (MMS) Mission seeks to measure heating and motion of charged particles from reconnection events in the magnetotail and dayside magnetopause. MMS is paralleled by the Terrestrial Reconnection Experiment (TREX) at the Wisconsin Plasma Astrophysics Laboratory (WiPAL) in its study of collisionless magnetic reconnection. In the regimes seen by TREX and MMS, electron pressure anisotropy should develop, driving large-scale current layer formation. MMS has witnessed anisotropy, but the spatial coverage of the data is too limited to determine how the pressure anisotropy affects jet and current layer creation. Measurements of pressure anisotropy on TREX will be presented, and implications for reconnecting current layer structure in the magnetosphere, as measured by MMS, will be discussed. This research was conducted with support from a UW-Madison University Fellowship as well as the NSF/DOE award DE-SC0013032.
2014-11-14
CAPE CANAVERAL, Fla. – The solar arrays on the Magnetospheric Multiscale, or MMS, observatories are uncovered for an inspection in the Building 1 D high bay of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the upper deck arrived Nov. 12; the two comprising the lower stack arrived Oct. 29. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-10-29
CAPE CANAVERAL, Fla. – Workers attach a crane to the protective shipping container to prepare to uncover the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS. They were delivered to the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Dan Casper
NASA Astrophysics Data System (ADS)
Miyajo, Akira; Hasegawa, Hideyuki
2018-07-01
At present, the speckle tracking method is widely used as a two- or three-dimensional (2D or 3D) motion estimator for the measurement of cardiovascular dynamics. However, this method requires high-level interpolation of a function, which evaluates the similarity between ultrasonic echo signals in two frames, to estimate a subsample small displacement in high-frame-rate ultrasound, which results in a high computational cost. To overcome this problem, a 2D motion estimator using the 2D Fourier transform, which does not require any interpolation process, was proposed by our group. In this study, we compared the accuracies of the speckle tracking method and our method using a 2D motion estimator, and applied the proposed method to the measurement of motion of a human carotid arterial wall. The bias error and standard deviation in the lateral velocity estimates obtained by the proposed method were 0.048 and 0.282 mm/s, respectively, which were significantly better than those (‑0.366 and 1.169 mm/s) obtained by the speckle tracking method. The calculation time of the proposed phase-sensitive method was 97% shorter than the speckle tracking method. Furthermore, the in vivo experimental results showed that a characteristic change in velocity around the carotid bifurcation could be detected by the proposed method.
30 CFR 1210.201 - How do I submit Form MMS-4430, Solid Minerals Production and Royalty Report?
Code of Federal Regulations, 2011 CFR
2011-07-01
...) Instructions for completing and submitting Form MMS-4430 are available on our Internet reporting web site or you may contact us toll free at 1-888-201-6416. (b) When to submit. (1) Unless your lease terms... month. (c) How to submit. (1) You must submit Form MMS-4430 electronically using our Internet reporting...
30 CFR 280.27 - When may MMS cancel my permit?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false When may MMS cancel my permit? 280.27 Section... Part Interrupted Activities § 280.27 When may MMS cancel my permit? The RD may cancel a permit at any time. (a) If we cancel your permit, the RD will advise you by certified or registered mail 30 days...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-06-01
... DEPARTMENT OF THE INTERIOR Minerals Management Service [Docket No. MMS-2008-MRM-0036] Notice Terminating the Exclusion of Indian Tribal Leases in the Uintah and Ouray Reservation From Valuation Under 30... the MMS Web site at http://www.mrm.mms.gov/TribServ/allzones.htm . The approved publications and index...
30 CFR 241.76 - Can MMS reduce my penalty once it is assessed?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Can MMS reduce my penalty once it is assessed? 241.76 Section 241.76 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR... Provisions § 241.76 Can MMS reduce my penalty once it is assessed? Under 30 U.S.C. 1719(g), the Director or...
30 CFR 250.124 - Will MMS approve gas injection into the cap rock containing a sulphur deposit?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Will MMS approve gas injection into the cap... SHELF General Performance Standards § 250.124 Will MMS approve gas injection into the cap rock containing a sulphur deposit? To receive the Regional Supervisor's approval to inject gas into the cap rock...
30 CFR 250.232 - What actions will MMS take after the EP is deemed submitted?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What actions will MMS take after the EP is deemed submitted? 250.232 Section 250.232 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF... Information Review and Decision Process for the Ep § 250.232 What actions will MMS take after the EP is deemed...
30 CFR 250.232 - What actions will MMS take after the EP is deemed submitted?
Code of Federal Regulations, 2011 CFR
2011-07-01
... 30 Mineral Resources 2 2011-07-01 2011-07-01 false What actions will MMS take after the EP is deemed submitted? 250.232 Section 250.232 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION... CONTINENTAL SHELF Plans and Information Review and Decision Process for the Ep § 250.232 What actions will MMS...
30 CFR 250.266 - After receiving the DPP or DOCD, what will MMS do?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false After receiving the DPP or DOCD, what will MMS do? 250.266 Section 250.266 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR... Decision Process for the Dpp Or Docd § 250.266 After receiving the DPP or DOCD, what will MMS do? (a...
30 CFR 250.233 - What decisions will MMS make on the EP and within what timeframe?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What decisions will MMS make on the EP and within what timeframe? 250.233 Section 250.233 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT... Information Review and Decision Process for the Ep § 250.233 What decisions will MMS make on the EP and within...
30 CFR 250.267 - What actions will MMS take after the DPP or DOCD is deemed submitted?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What actions will MMS take after the DPP or DOCD is deemed submitted? 250.267 Section 250.267 Mineral Resources MINERALS MANAGEMENT SERVICE... and Information Review and Decision Process for the Dpp Or Docd § 250.267 What actions will MMS take...
MMS Partial Solar Array Inspection
2014-11-14
A plaque affixed to the side of a Magnetospheric Multiscale, or MMS, observatory dedicates the mission to Richard “Richy” D’Antonio, now deceased, in grateful appreciation for his dedicated service to NASA’s MMS mission. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
MMS Partial Solar Array Inspection
2014-11-14
A plaque affixed to the side of a Magnetospheric Multiscale, or MMS, observatory dedicates the mission to Dr. John William Klein, now deceased, who served the MMS team as the standing review board chairman. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
MMS Partial Solar Array Inspection
2014-11-14
A plaque affixed to the side of a Magnetospheric Multiscale, or MMS, observatory dedicates the mission to George S. Moore, now deceased, an engineer who was a beloved colleague and friend to the MMS team. MMS, led by a team from NASA's Goddard Space Flight Center, is a Solar Terrestrial Probes mission consisting of four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
57Fe CEMS study on dilute metal ions codoped SnO2 thin films prepared by spray pyrolysis
NASA Astrophysics Data System (ADS)
Nomura, Kiyoshi; Koike, Yuya; Nakanishi, Akio
2017-11-01
Dilute Mn-Fe, Co-Fe and V-Fe codoped tin oxide films prepared by spray pyrolysis were characterized by 57Fe conversion electron Mössbauer spectrometry (CEMS) at room temperature (RT) and at 20 K. Two kinds of paramagnetic Fe3+ species were detected at RT; one doublet 1 (D1) with IS = 0.36-0.37 mm/s, QS = 0.69-0.75 mm/s and LW = 0.32-0.40 mm/s, and another doublet 2 (D2) with IS = 0.31-0.35 mm/s QS = 1.16-1.25 mm/s and LW = 0.46-0.52 mm/s. CEMS at 20 K provided more distinguished doublets than at RT. It is found that especially D2 with relatively small IS and large QS values are influenced by other metal ions codoped in SnO2 matrix, whereas D1 with relatively large IS and small QS has the parameters close to the models of Fe-VO1 and Fe-2VO1-Fe models (Nomura et al. Phys. Rev. B 75, 184411 2007; Mudarra Navarro et al. J. Phys. Chem. C 119, 5596-5603 2015).
David, Stephanie; Passirani, Catherine; Carmoy, Nathalie; Morille, Marie; Mevel, Mathieu; Chatin, Benoit; Benoit, Jean-Pierre; Montier, Tristan; Pitard, Bruno
2013-01-01
We hereby present different DNA nanocarriers consisting of new multimodular systems (MMS), containing the cationic lipid dioleylaminesuccinylparomomycin (DNA MMS DOSP), or bis (guanidinium)-tren-cholesterol (DNA MMS BGTC), and DNA lipid nanocapsules (DNA LNCs). Active targeting of the asialoglycoprotein receptor (ASGP-R) using galactose as a ligand for DNA MMS (GAL DNA MMS) and passive targeting using a polyethylene glycol coating for DNA LNCs (PEG DNA LNCs) should improve the properties of these DNA nanocarriers. All systems were characterized via physicochemical methods and the DNA payload of DNA LNCs was quantified for the first time. Afterwards, their biodistribution in healthy mice was analyzed after encapsulation of a fluorescent dye via in vivo biofluorescence imaging (BFI), revealing various distribution profiles depending on the cationic lipid used and their surface characteristics. Furthermore, the two vectors with the best prolonged circulation profile were administered twice in healthy mice revealing that the new DNA MMS DOSP vectors showed no toxicity and the same distribution profile for both injections, contrary to PEG DNA LNCs which showed a rapid clearance after the second injection, certainly due to the accelerated blood clearance phenomenon. PMID:23299832
Burgos, Jose L.; Patterson, Thomas L.; Graff-Zivin, Joshua S.; Kahn, James G.; Rangel, M. Gudelia; Lozada, M. Remedios; Staines, Hugo; Strathdee, Steffanie A.
2016-01-01
Background We evaluated the cost-effectiveness of combined single session brief behavioral intervention, either didactic or interactive (Mujer Mas Segura, MMS) to promote safer-sex and safer-injection practices among female sex workers who inject drugs (FSW-IDUs) in Tijuana (TJ) and Ciudad-Juarez (CJ) Mexico. Data for this analysis was obtained from a factorial RCT in 2008–2010 coinciding with expansion of needle exchange programs (NEP) in TJ, but not in CJ. Methods A Markov model was developed to estimate the incremental cost per quality adjusted life year gained (QALY) over a lifetime time frame among a hypothetical cohort of 1,000 FSW-IDUs comparing a less intensive didactic vs. a more intensive interactive format of the MMS, separately for safer sex and safer injection combined behavioral interventions. The costs for antiretroviral therapy was not included in the model. We applied a societal perspective, a discount rate of 3% per year and currency adjusted to US$2014. A multivariate sensitivity analysis was performed. The combined and individual components of the MMS interactive behavioral intervention were compared with the didactic formats by calculating the incremental cost-effectiveness ratios (ICER), defined as incremental unit of cost per additional health benefit (e.g., HIV/STI cases averted, QALYs) compared to the next least costly strategy. Following guidelines from the World Health Organization, a combined strategy was considered highly cost-effective if the incremental cost per QALY gained fell below the gross domestic product per capita (GDP) in Mexico (equivalent to US$10,300). Findings For CJ, the mixed intervention approach of interactive safer sex/didactic safer injection had an incremental cost-effectiveness ratio (ICER) of US$4,360 ($310–$7,200) per QALY gained compared with a dually didactic strategy. Using the dually interactive strategy had an ICER of US$5,874 ($310–$7,200) compared with the mixed approach. For TJ, the combination of interactive safer sex/didactic safer injection had an ICER of US$5,921 ($104–$9,500) per QALY compared with dually didactic. Strategies using the interactive safe injection intervention were dominated due to lack of efficacy advantage. The multivariate sensitivity analysis showed a 95% certainty that in both CJ and TJ the ICER for the mixed approach (interactive safer sex didactic safer injection intervention) was less than the GDP per capita for Mexico. The dual interactive approach met this threshold consistently in CJ, but not in TJ. Interpretation In the absence of an expanded NEP in CJ, the combined-interactive formats of the MMS behavioral intervention is highly cost-effective. In contrast, in TJ where NEP expansion suggests that improved access to sterile syringes significantly reduced injection-related risks, the interactive safer-sex combined didactic safer-injection was highly cost-effective compared with the combined didactic versions of the safer-sex and safer-injection formats of the MMS, with no added benefit from the interactive safer-injection component. PMID:26890001
NASA Astrophysics Data System (ADS)
Jia, Yali; An, Lin; Wang, Ruikang K.
2010-05-01
We demonstrate for the first time that the detailed blood flow distribution within intracranial dura mater and cortex can be visualized by an ultrahigh sensitive optical microangiography (UHS-OMAG). The study uses an UHS-OMAG system operating at 1310 nm with an imaging speed at 150 frames per second that requires ~10 s to complete one 3-D scan of ~2.5×2.5 mm2. The system is sensitive to blood flow with a velocity ranging from ~4 μm/s to ~23 mm/s. We show superior performance of UHS-OMAG in providing functional images of capillary level microcirculation within meninges in mice with the cranium left intact, the results of which correlate well with the standard dural histopathology.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sargentini, N.J.; Smith, K.C.
1983-03-01
After N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis of Escherichia coli K-12 (xthA14), an X-ray-sensitive mutant was isolated. This sensitivity is due to a mutation, radB101, which is located at 56.5 min on the E.coli K-12 linkage map. The radB101 mutation sensitized wild-type cells to ..gamma.. and uv radiation, and to methyl methanesulfonate. When known DNA repair-deficient mutants were ranked for their ..gamma..-radiation sensitivity relative to their uv-radiation sensitivity, their order was (starting with the most selectively ..gamma..-radiation-sensitive strain): recB21, radB101, wild type, polA1, recF143, lexA101, recA56, uvrD3, and uvrA6. The radB mutant was normal for ..gamma..- and uv-radiation mutagenesis, it showed only a slightmore » enhancement of ..gamma..- and uv-radiation-induced DNA degradation, and it was approx. 60% deficient in recombination ability. The radB gene is suggested to play a role in the recA gene-dependent (Type III) repair of DNA single-strand breaks after ..gamma.. irradiation and in postreplication repair after uv irradiation for the following reasons: the radB strain was normal for the host-cell reactivation of ..gamma..- and uv-irradiated bacteriophage lambda; the radB mutation did not sensitize a recA strain, but did sensitize a polA strain to ..gamma.. and uv radiation; the radB mutation sensitized a uvrB strain to uv radiation.« less
Vitha, Stanislav; Yang, Ming; Kiss, John Z.; Sack, Fred D.
1998-01-01
Dark-grown hypocotyls of a starch-deficient mutant (NS458) of tobacco (Nicotiana sylvestris) lack amyloplasts and plastid sedimentation, and have severely reduced gravitropism. However, gravitropism improved dramatically when NS458 seedlings were grown in the light. To determine the extent of this improvement and whether mutant hypocotyls contain sedimented amyloplasts, gravitropic sensitivity (induction time and intermittent stimulation) and plastid size and position in the endodermis were measured in seedlings grown for 8 d in the light. Light-grown NS458 hypocotyls were gravitropic but were less sensitive than the wild type (WT). Starch occupied 10% of the volume of NS458 plastids grown in both the light and the dark, whereas WT plastids were essentially filled with starch in both treatments. Light increased plastid size twice as much in the mutant as in the WT. Plastids in light-grown NS458 were sedimented, presumably because of their larger size and greater total starch content. The induction by light of plastid sedimentation in NS458 provides new evidence for the role of plastid mass and sedimentation in stem gravitropic sensing. Because the mutant is not as sensitive as the WT, NS458 plastids may not have sufficient mass to provide full gravitropic sensitivity. PMID:9490754
NASA Technical Reports Server (NTRS)
Vitha, S.; Yang, M.; Kiss, J. Z.; Sack, F. D.
1998-01-01
Dark-grown hypocotyls of a starch-deficient mutant (NS458) of tobacco (Nicotiana sylvestris) lack amyloplasts and plastid sedimentation, and have severely reduced gravitropism. However, gravitropism improved dramatically when NS458 seedlings were grown in the light. To determine the extent of this improvement and whether mutant hypocotyls contain sedimented amyloplasts, gravitropic sensitivity (induction time and intermittent stimulation) and plastid size and position in the endodermis were measured in seedlings grown for 8 d in the light. Light-grown NS458 hypocotyls were gravitropic but were less sensitive than the wild type (WT). Starch occupied 10% of the volume of NS458 plastids grown in both the light and the dark, whereas WT plastids were essentially filled with starch in both treatments. Light increased plastid size twice as much in the mutant as in the WT. Plastids in light-grown NS458 were sedimented, presumably because of their larger size and greater total starch content. The induction by light of plastid sedimentation in NS458 provides new evidence for the role of plastid mass and sedimentation in stem gravitropic sensing. Because the mutant is not as sensitive as the WT, NS458 plastids may not have sufficient mass to provide full gravitropic sensitivity.
Tolerance of an Antarctic Bacterium to Multiple Environmental Stressors.
Sengupta, Dipanwita; Sangu, Kavya; Shivaji, Sisinthy; Chattopadhyay, Madhab K
2015-10-01
A population of cold-tolerant Antarctic bacteria was screened for their ability to tolerate other environmental stress factors. Besides low temperature, they were predominantly found to be tolerant to alkali. Attempt was also made to postulate a genetic basis of their multistress-tolerance. Transposon mutagenesis of an isolate Pseudomonas syringae Lz4W was performed, and mutants with delayed growth at low temperature were further screened for sensitivity to some other stress factors. A number of multistress-sensitive mutants were isolated. The mutated gene in one of the mutants sensitive to low temperature, acid and alkali was found to encode citrate synthase. Possible role of citrate synthase in conferring multistress-tolerance was postulated.
Frey, T; Newlin, L L; Atherly, A G
1975-01-01
A mutant of Escherichia coli has been isolated that has a temperature-sensitive mutation that results in specific loss of ribosomal ribonucleic acid (RNA) synthesis and some reduction in messenger RNA synthesis. When the strain was grown in glucose medium at a restrictive temperature, RNA accumulation ceased, but both messenger RNA and protein synthesis continued for an extended time. Because carbon metabolism was slowed drastically when strain AA-157 was placed at the restrictive temperature, this phenotype can be compared with carbon depletion conditions present during diauxic lag. However, the phenotype of mutant AA-157 differs from shift-down conditions in that guanosine-3',5'-tetraphosphate levels are unaffected; therefore, a different site is affected. This mutant strain (AA-157) thus shows many characteristics similar to an aldolase mutant previously reported (Böck and Neidhardt, 1966). However, the mutation occurred in a different position on the E. coli genetic map, and furthermore, aldolase was not temperature sensitive in strain AA-157. In this paper we present a study of macromolecular biosynthesis in this mutant. PMID:1090609
Suzuki, E; Kondo, T; Makise, M; Mima, S; Sakamoto, K; Tsuchiya, T; Mizushima, T
1998-07-01
We previously reported that mutations in the dnaA gene which encodes the initiator of chromosomal DNA replication in Escherichia coli caused an alteration in the levels of unsaturated fatty acids of phospholipids in membranes. In this study, we examined fatty acid compositions in other mutants which are defective in DNA replication. As in the case of temperature-sensitive dnaA mutants, temperature-sensitive dnaC and dnaE mutants, which have defects in initiation and elongation, respectively, of DNA replication showed a lower level of unsaturation of fatty acids (ratio of unsaturated to saturated fatty acids) compared with the wild-type strain, especially at high temperatures. On the other hand, temperature-sensitive mutants defective in cellular processes other than DNA replication, such as RNA synthesis and cell division, did not show a lower level of unsaturation of fatty acids compared with the wild-type strain. These results suggest that the inhibition of DNA replication causes a lower level of unsaturation of fatty acids in Escherichia coli cells.
Alteration in the contents of unsaturated fatty acids in dnaA mutants of Escherichia coli.
Suzuki, E; Kondo, T; Makise, M; Mima, S; Sakamoto, K; Tsuchiya, T; Mizushima, T
1998-04-01
DnaA protein, the initiator of chromosomal DNA replication in Escherichia coli, has a high affinity for acidic phospholipids containing unsaturated fatty acids. We have examined here the fatty acid composition of phospholipids in dnaA mutants. A temperature-sensitive dnaA46 mutant showed a lower level of unsaturation of fatty acids (ratio of unsaturated to saturated fatty acids) at 42 degrees C (non-permissive temperature) and at 37 degrees C (semi-permissive temperature), but not at 28 degrees C (permissive temperature), compared with the wild-type strain. Plasmid complementation analysis revealed that the dnaA46 mutation is responsible for the phenotype. Other temperature-sensitive dnaA mutants showed similar results. On the other hand, a cold-sensitive dnaAcos mutant, in which over-initiation of DNA replication occurs at low temperature (28 degrees C), showed a higher level of unsaturation of fatty acids at 28 degrees C. Based on these observations, we discuss the role of phospholipids in the regulation of the activity of DnaA protein.
Diago-Navarro, Elizabeth; Mora, Liliana; Buckingham, Richard H; Díaz-Orejas, Ramón; Lemonnier, Marc
2009-01-01
Novel mutations in prfA, the gene for the polypeptide release factor RF1 of Escherichia coli, were isolated using a positive genetic screen based on the parD (kis, kid) toxin-antitoxin system. This original approach allowed the direct selection of mutants with altered translational termination efficiency at UAG codons. The isolated prfA mutants displayed a approximately 10-fold decrease in UAG termination efficiency with no significant changes in RF1 stability in vivo. All three mutations, G121S, G301S and R303H, were situated close to the nonsense codon recognition site in RF1:ribosome complexes. The prfA mutants displayed increased sensitivity to the RelE toxin encoded by the relBE system of E. coli, thus providing in vivo support for the functional interaction between RF1 and RelE. The prfA mutants also showed increased sensitivity to the Kid toxin. Since this toxin can cleave RNA in a ribosome-independent manner, this result was not anticipated and provided first evidence for the involvement of RF1 in the pathway of Kid toxicity. The sensitivity of the prfA mutants to RelE and Kid was restored to normal levels upon overproduction of the wild-type RF1 protein. We discuss these results and their utility for the design of novel antibacterial strategies in the light of the recently reported structure of ribosome-bound RF1.
30 CFR 203.66 - What happens if MMS does not act in the time allowed?
Code of Federal Regulations, 2010 CFR
2010-07-01
... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What happens if MMS does not act in the time... Relief for Pre-Act Deep Water Leases and for Development and Expansion Projects § 203.66 What happens if MMS does not act in the time allowed? If we do not act within the timeframes established under § 203...
Characterization of Escherichia coli d-Cycloserine Transport and Resistant Mutants
Baisa, Gary; Stabo, Nicholas J.
2013-01-01
d-Cycloserine (DCS) is a broad-spectrum antibiotic that inhibits d-alanine ligase and alanine racemase activity. When Escherichia coli K-12 or CFT073 is grown in minimal glucose or glycerol medium, CycA transports DCS into the cell. E. coli K-12 cycA and CFT073 cycA mutant strains display increased DCS resistance when grown in minimal medium. However, the cycA mutants exhibit no change in DCS sensitivity compared to their parental strains when grown in LB (CFT073 and K-12) or human urine (CFT073 only). These data suggest that cycA does not participate in DCS sensitivity when strains are grown in a non-minimal medium. The small RNA GvcB acts as a negative regulator of E. coli K-12 cycA expression when grown in LB. Three E. coli K-12 gcvB mutant strains failed to demonstrate a change in DCS sensitivity when grown in LB. This further suggests a limited role for cycA in DCS sensitivity. To aid in the identification of E. coli genes involved in DCS sensitivity when grown on complex media, the Keio K-12 mutant collection was screened for DCS-resistant strains. dadA, pnp, ubiE, ubiF, ubiG, ubiH, and ubiX mutant strains showed elevated DCS resistance. The phenotypes associated with these mutants were used to further define three previously characterized E. coli DCS-resistant strains (χ316, χ444, and χ453) isolated by Curtiss and colleagues (R. Curtiss, III, L. J. Charamella, C. M. Berg, and P. E. Harris, J. Bacteriol. 90:1238–1250, 1965). A dadA mutation was identified in both χ444 and χ453. In addition, results are presented that indicate for the first time that DCS can antagonize d-amino acid dehydrogenase (DadA) activity. PMID:23316042
McDaniel, Cameron; Su, Shengchang; Panmanee, Warunya; Lau, Gee W.; Browne, Tristan; Cox, Kevin; Paul, Andrew T.; Ko, Seung-Hyun B.; Mortensen, Joel E.; Lam, Joseph S.; Muruve, Daniel A.; Hassett, Daniel J.
2016-01-01
Pseudomonas aeruginosa (PA) is an important airway pathogen of cystic fibrosis and chronic obstructive disease patients. Multiply drug resistant PA is becoming increasing prevalent and new strategies are needed to combat such insidious organisms. We have previously shown that a mucoid, mucA22 mutant PA is exquisitely sensitive to acidified nitrite (A-NO2−, pH 6.5) at concentrations that are well tolerated in humans. Here, we used a transposon mutagenesis approach to identify PA mutants that are hypersensitive to A-NO2−. Among greater than 10,000 mutants screened, we focused on PA4455, in which the transposon was found to disrupt the production of a putative cytoplasmic membrane-spanning ABC transporter permease. The PA4455 mutant was not only highly sensitive to A-NO2−, but also the membrane perturbing agent, EDTA and the antibiotics doxycycline, tigecycline, colistin, and chloramphenicol, respectively. Treatment of bacteria with A-NO2− plus EDTA, however, had the most dramatic and synergistic effect, with virtually all bacteria killed by 10 mM A-NO2−, and EDTA (1 mM, aerobic, anaerobic). Most importantly, the PA4455 mutant was also sensitive to A-NO2− in biofilms. A-NO2− sensitivity and an anaerobic growth defect was also noted in two mutants (rmlC and wbpM) that are defective in B-band LPS synthesis, potentially indicating a membrane defect in the PA4455 mutant. Finally, this study describes a gene, PA4455, that when mutated, allows for dramatic sensitivity to the potential therapeutic agent, A-NO2− as well as EDTA. Furthermore, the synergy between the two compounds could offer future benefits against antibiotic resistant PA strains. PMID:27064218
Monopoles, cosmology, and astrophysics - Update 1985
NASA Technical Reports Server (NTRS)
Turner, Michael S.
1986-01-01
The characteristics of the superheavy magnetic monopoles (MMs) predicted by GUTs are reviewed, and recent developments in astrophysical MM search techniques are surveyed. Theoretical models of the birth, current distribution, and motion of MMs are examined; the observational implications of MM mass, magnetic charge, and ability to catalyze nucleon decay are considered; estimates of the average and local flux limits for MMs of 10 to the 25th eV are given (less than about 3 x 10 to the -15th and less than about 3 x 10 to the -11th/sq cm sr sec, respectively); and the possibility of detecting MMs in the sun (if they can escape annihilation there) is discussed.
MMS Spacecraft Uncrated & Moved
2014-10-29
Two of the observatories, the lower stack, mini-stack number 1, for NASA's Magnetospheric Multiscale Observatory, or MMS, arrive in the Building 1 airlock at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
2014-10-30
Technicians remove the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
MMS Spacecraft Uncrated & Moved
2014-10-29
Two of the observatories, the lower stack, mini-stack number 1, for NASA's Magnetospheric Multiscale Observatory, or MMS, roll into the Building 1 airlock at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
MMS Spacecraft Uncrated & Moved
2014-10-29
Workers position two of the observatories, the lower stack, mini-stack number 1 for NASA's Magnetospheric Multiscale Observatory, or MMS, onto a payload dolly in the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
Magnetospheric Multiscale (MMS)
2014-05-09
Propulsion engineer measures the flight filters during the receiving inspection. Learn more about MMS at www.nasa.gov/mms Credit NASA/Goddard The Magnetospheric Multiscale, or MMS, will study how the sun and the Earth's magnetic fields connect and disconnect, an explosive process that can accelerate particles through space to nearly the speed of light. This process is called magnetic reconnection and can occur throughout all space. 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
On the calibration and use of Dual Electron Sensors for NASA's Magnetospheric MultiScale mission
NASA Astrophysics Data System (ADS)
Avanov, L. A.; Gliese, U.; Pollock, C. J.; Barrie, A.; Mariano, A. J.; Tucker, C. J.; Jacques, A. D.; Zeuch, M.; Shields, N.; Christian, K. D.
2013-12-01
The scientific target of NASA's Magnetospheric MultiScale (MMS) mission is to study the fundamentally important phenomenon of magnetic reconnection. Theoretical models of this process predict a small (order of ten kilometers) size for the diffusion region where electrons are demagnetized at the dayside magnetopause. Yet, the region may typically sweep over the spacecraft at relatively high speeds of 50km/s. That is why Fast Plasma Investigation (FPI) instrument suite must have extremely high time resolution for measurements of the 3D particle distribution functions. The Dual Electron Spectrometers (DESs) provide fast (30ms) 3D electron velocity distributions, from 10eV to 30,000 eV, as part of the Fast Plasma Investigation (FPI) on NASA's Magnetospheric MultiScale (MMS) mission. This is accomplished by combining the measurements from eight different spectrometers (packaged in four dual sets) on each MMS spacecraft to produce each full distribution. This approach presents a new and challenging aspect to the calibration and operation of these instruments. The response uniformity among the spectrometer set, the consistency and reliability of their calibration in both sensitivity and their phase space selectivity (energy and angle), and the approach to handling any temporal evolution of these calibrated characteristics all assume enhanced importance in this application. In this paper, we will present brief descriptions of the spectrometers and our approach their ground calibration, trended results of those calibrations, and our plans to detect, track, and respond to any temporal evolution in instrument performance through the life of the mission.
Method for rapid isolation of sensitive mutants
Freyer, James P.
1997-01-01
Sensitive mammalian cell mutants are rapidly isolated using flow cytometry. A first population of clonal spheroids is established to contain both normal and mutant cells. The population may be naturally occurring or may arise from mutagenized cells. The first population is then flow sorted by size to obtain a second population of clonal spheroids of a first uniform size. The second population is then exposed to a DNA-damaging agent that is being investigated. The exposed second population is placed in a growth medium to form a third population of clonal spheroids comprising spheroids of increased size from the mammalian cells that are resistant to the DNA-damaging agent and spheroids of substantially the first uniform size formed from the mammalian cells that are sensitive to the DNA-damaging agent. The third population is not flow sorted to differentiate the spheroids formed from resistant mammalian cells from spheroids formed from sensitive mammalian cells. The spheroids formed from sensitive mammalian cells are now treated to recover viable sensitive cells from which a sensitive cell line can be cloned.
Method for rapid isolation of sensitive mutants
Freyer, J.P.
1997-07-29
Sensitive mammalian cell mutants are rapidly isolated using flow cytometry. A first population of clonal spheroids is established to contain both normal and mutant cells. The population may be naturally occurring or may arise from mutagenized cells. The first population is then flow sorted by size to obtain a second population of clonal spheroids of a first uniform size. The second population is then exposed to a DNA-damaging agent that is being investigated. The exposed second population is placed in a growth medium to form a third population of clonal spheroids comprising spheroids of increased size from the mammalian cells that are resistant to the DNA-damaging agent and spheroids of substantially the first uniform size formed from the mammalian cells that are sensitive to the DNA-damaging agent. The third population is not flow sorted to differentiate the spheroids formed from resistant mammalian cells from spheroids formed from sensitive mammalian cells. The spheroids formed from sensitive mammalian cells are now treated to recover viable sensitive cells from which a sensitive cell line can be cloned. 15 figs.
Realization of planning design of mechanical manufacturing system by Petri net simulation model
NASA Astrophysics Data System (ADS)
Wu, Yanfang; Wan, Xin; Shi, Weixiang
1991-09-01
Planning design is to work out a more overall long-term plan. In order to guarantee a mechanical manufacturing system (MMS) designed to obtain maximum economical benefit, it is necessary to carry out a reasonable planning design for the system. First, some principles on planning design for MMS are introduced. Problems of production scheduling and their decision rules for computer simulation are presented. Realizable method of each production scheduling decision rule in Petri net model is discussed. Second, the solution of conflict rules for conflict problems during running Petri net is given. Third, based on the Petri net model of MMS which includes part flow and tool flow, according to the principle of minimum event time advance, a computer dynamic simulation of the Petri net model, that is, a computer dynamic simulation of MMS, is realized. Finally, the simulation program is applied to a simulation exmple, so the scheme of a planning design for MMS can be evaluated effectively.
Artificial Roughness Encoding with a Bio-inspired MEMS- based Tactile Sensor Array
Oddo, Calogero Maria; Beccai, Lucia; Felder, Martin; Giovacchini, Francesco; Carrozza, Maria Chiara
2009-01-01
A compliant 2×2 tactile sensor array was developed and investigated for roughness encoding. State of the art cross shape 3D MEMS sensors were integrated with polymeric packaging providing in total 16 sensitive elements to external mechanical stimuli in an area of about 20 mm2, similarly to the SA1 innervation density in humans. Experimental analysis of the bio-inspired tactile sensor array was performed by using ridged surfaces, with spatial periods from 2.6 mm to 4.1 mm, which were indented with regulated 1N normal force and stroked at constant sliding velocity from 15 mm/s to 48 mm/s. A repeatable and expected frequency shift of the sensor outputs depending on the applied stimulus and on its scanning velocity was observed between 3.66 Hz and 18.46 Hz with an overall maximum error of 1.7%. The tactile sensor could also perform contact imaging during static stimulus indentation. The experiments demonstrated the suitability of this approach for the design of a roughness encoding tactile sensor for an artificial fingerpad. PMID:22412304
A flexible slip sensor using triboelectric nanogenerator approach
NASA Astrophysics Data System (ADS)
Wang, Xudong; Liang, Jiaming; Xiao, Yuxiang; Wu, Yichuan; Deng, Yang; Wang, Xiaohao; Zhang, Min
2018-03-01
With the rapid development of robotic technology, tactile sensors for robots have gained great attention from academic and industry researchers. Tactile sensors for slip detection are essential for human-like steady control in dexterous robot hand. In this paper, we propose and demonstrate a flexible slip sensor based on triboelectric nanogenerator with a seesaw structure. The sensor is composed of two porous PDMS layers separated by an inverted trapezoid structure with a height of 500 μm. In order to customize the sensitivity of the sensor, porous PDMS was fabricated by mixing PDMS with deionized water thoroughly and then removing water with heat. Laser-induced porous graphene and aluminium are served as the pair of contact materials. To detect slip from different directions, two sets of the electrode pair were used. Experimental results show a distinct difference between static state and the moment when a slip happens was detected. In addition, the output voltage of the sensors increased as the increase of slip velocity from 0.25 mm/s to 2.5 mm/s. The flexible slip sensor proposed here shows the potential applications in smart robotics and prosthesis.
Dynamic Fracture Behavior of Steel Fiber Reinforced Self-Compacting Concretes (SFRSCCs).
Zhang, Xiaoxin; Ruiz, Gonzalo; Tarifa, Manuel; Cendón, David; Gálvez, Francisco; Alhazmi, Waleed H
2017-11-05
Three-point bending tests on notched beams of three types of steel fiber-reinforced self-compacting concrete (SFRSCC) have been performed by using both a servo-hydraulic machine and a drop-weight impact instrument. The lo ading rates had a range of six orders of magnitude from 2.20 × 10 -3 mm/s (quasi-static) to 2.66 × 10³ mm/s. These SFRSCCs had the same matrix, but various types of steel fiber (straight and hooked-end) and contents (volume ratios), 0.51%, 0.77% and 1.23%, respectively. The results demonstrate that the fracture energy and the flexural strength increase as the loading rate increases. Moreover, such tendency is relatively moderate at low rates. However, at high rates it is accentuated. For the 0.51% fiber content, the dynamic increase factors of the flexural strength and the fracture energy are approximately 6 and 3, while for the 1.23% fiber content, they are around 4 and 2, respectively. Thus, the higher the fiber content the less rate sensitivity there is.
Dynamic Fracture Behavior of Steel Fiber Reinforced Self-Compacting Concretes (SFRSCCs)
Tarifa, Manuel; Cendón, David; Gálvez, Francisco; Alhazmi, Waleed H.
2017-01-01
Three-point bending tests on notched beams of three types of steel fiber-reinforced self-compacting concrete (SFRSCC) have been performed by using both a servo-hydraulic machine and a drop-weight impact instrument. The lo ading rates had a range of six orders of magnitude from 2.20 × 10−3 mm/s (quasi-static) to 2.66 × 103 mm/s. These SFRSCCs had the same matrix, but various types of steel fiber (straight and hooked-end) and contents (volume ratios), 0.51%, 0.77% and 1.23%, respectively. The results demonstrate that the fracture energy and the flexural strength increase as the loading rate increases. Moreover, such tendency is relatively moderate at low rates. However, at high rates it is accentuated. For the 0.51% fiber content, the dynamic increase factors of the flexural strength and the fracture energy are approximately 6 and 3, while for the 1.23% fiber content, they are around 4 and 2, respectively. Thus, the higher the fiber content the less rate sensitivity there is. PMID:29113095
Seroz, T; Winkler, G S; Auriol, J; Verhage, R A; Vermeulen, W; Smit, B; Brouwer, J; Eker, A P; Weeda, G; Egly, J M; Hoeijmakers, J H
2000-11-15
Nucleotide excision repair (NER) removes UV-induced photoproducts and numerous other DNA lesions in a highly conserved 'cut-and-paste' reaction that involves approximately 25 core components. In addition, several other proteins have been identified which are dispensable for NER in vitro but have an undefined role in vivo and may act at the interface of NER and other cellular processes. An intriguing example is the Saccharomyces cerevisiae Mms19 protein that has an unknown dual function in NER and RNA polymerase II transcription. Here we report the cloning and characterization of a human homolog, designated hMMS19, that encodes a 1030 amino acid protein with 26% identity and 51% similarity to S.cerevisiae Mms19p and with a strikingly similar size. The expression profile and nuclear location are consistent with a repair function. Co-immunoprecipitation experiments revealed that hMMS19 directly interacts with the XPB and XPD subunits of NER-transcription factor TFIIH. These findings extend the conservation of the NER apparatus and the link between NER and basal transcription and suggest that hMMS19 exerts its function in repair and transcription by interacting with the XPB and XPD helicases.
NASA Astrophysics Data System (ADS)
Resdiansyah; O. K Rahmat, R. A.; Ismail, A.
2018-03-01
Green transportation refers to a sustainable transport that gives the least impact in terms of social and environmental but at the same time is able to supply energy sources globally that includes non-motorized transport strategies deployment to promote healthy lifestyles, also known as Mobility Management Scheme (MMS). As construction of road infrastructure cannot help solve the problem of congestion, past research has shown that MMS is an effective measure to mitigate congestion and to achieve green transportation. MMS consists of different strategies and policies that subdivided into categories according to how they are able to influence travel behaviour. Appropriate selection of mobility strategies will ensure its effectiveness in mitigating congestion problems. Nevertheless, determining appropriate strategies requires human expert and depends on a number of success factors. This research has successfully developed a computer clone system based on human expert, called E-MMS. The process of knowledge acquisition for MMS strategies and the next following process to selection of strategy has been encode in a knowledge-based system using a shell expert system. The newly developed computer cloning system was successfully verified, validated and evaluated (VV&E) by comparing the result output with the real transportation expert recommendation in which the findings suggested Introduction
NASA Astrophysics Data System (ADS)
Madhotra, Ravi; Raouf, A.; Sturgess, R.; Krasner, Neville
1997-12-01
Re-establishment of the oesophageal lumen is the main focus of care in patients with inoperable oesophageal carcinomas. The self-expanding metal mesh stents (MMS) are increasingly being used. 51 patients aged 44 - 89 with inoperable oesophago-gastric carcinomas were intubated with MMS. 18 of these patients had endoscopic laser therapy (ELT) as primary palliation. 25 patients required follow-up endoscopy at variable intervals after stent insertion. 17 patients were found to have significant tumor growth (9), overgrowth (4) and both (4). All these patients were treated with Nd:YAG or diode laser for maintenance of satisfactory swallowing. 4 patients being treated with Nd:YAG laser developed deformity of MMS. This complication was not encountered with diode laser. The reblockage of MMS due to ingrowth or overgrowth of tumor is a not uncommon complication. The timing of the stent insertion should be carefully chosen since the longer the stent is in situ, the greater is the likelihood of tumor ingrowth or overgrowth. ELT can effectively deal with tumor ingrowth and overgrowth. Nd:YAG laser can cause melting of MMS. Overall the combination of ELT and MMS may offer the best palliation, particularly when patient survival of several months is anticipated.
David, Stephanie; Passirani, Catherine; Carmoy, Nathalie; Morille, Marie; Mevel, Mathieu; Chatin, Benoit; Benoit, Jean-Pierre; Montier, Tristan; Pitard, Bruno
2013-01-08
We hereby present different DNA nanocarriers consisting of new multimodular systems (MMS), containing the cationic lipid dioleylaminesuccinylparomomycin (DNA MMS DOSP), or bis (guanidinium)-tren-cholesterol (DNA MMS BGTC), and DNA lipid nanocapsules (DNA LNCs). Active targeting of the asialoglycoprotein receptor (ASGP-R) using galactose as a ligand for DNA MMS (GAL DNA MMS) and passive targeting using a polyethylene glycol coating for DNA LNCs (PEG DNA LNCs) should improve the properties of these DNA nanocarriers. All systems were characterized via physicochemical methods and the DNA payload of DNA LNCs was quantified for the first time. Afterwards, their biodistribution in healthy mice was analyzed after encapsulation of a fluorescent dye via in vivo biofluorescence imaging (BFI), revealing various distribution profiles depending on the cationic lipid used and their surface characteristics. Furthermore, the two vectors with the best prolonged circulation profile were administered twice in healthy mice revealing that the new DNA MMS DOSP vectors showed no toxicity and the same distribution profile for both injections, contrary to PEG DNA LNCs which showed a rapid clearance after the second injection, certainly due to the accelerated blood clearance phenomenon.Molecular Therapy - Nucleic Acids (2013) 2, e64; doi:10.1038/mtna.2012.56; published online 8 January 2013.
Modular Manufacturing Simulator: Users Manual
NASA Technical Reports Server (NTRS)
1997-01-01
The Modular Manufacturing Simulator (MMS) has been developed for the beginning user of computer simulations. Consequently, the MMS cannot model complex systems that require branching and convergence logic. Once a user becomes more proficient in computer simulation and wants to add more complexity, the user is encouraged to use one of the many available commercial simulation systems. The (MMS) is based on the SSE5 that was developed in the early 1990's by the University of Alabama in Huntsville (UAH). A recent survey by MSFC indicated that the simulator has been a major contributor to the economic impact of the MSFC technology transfer program. Many manufacturers have requested additional features for the SSE5. Consequently, the following features have been added to the MMS that are not available in the SSE5: runs under Windows, print option for both input parameters and output statistics, operator can be fixed at a station or assigned to a group of stations, operator movement based on time limit, part limit, or work-in-process (WIP) limit at next station. The movement options for a moveable operators are: go to station with largest WIP, rabbit chase where operator moves in circular sequence between stations, and push/pull where operator moves back and forth between stations. This user's manual contains the necessary information for installing the MMS on a PC, a description of the various MMS commands, and the solutions to a number of sample problems using the MMS. Also included in the beginning of this report is a brief discussion of technology transfer.
Zhukova, Nataliya; Ramaswamy, Vijay; Remke, Marc; Martin, Dianna C; Castelo-Branco, Pedro; Zhang, Cindy H; Fraser, Michael; Tse, Ken; Poon, Raymond; Shih, David J H; Baskin, Berivan; Ray, Peter N; Bouffet, Eric; Dirks, Peter; von Bueren, Andre O; Pfaff, Elke; Korshunov, Andrey; Jones, David T W; Northcott, Paul A; Kool, Marcel; Pugh, Trevor J; Pomeroy, Scott L; Cho, Yoon-Jae; Pietsch, Torsten; Gessi, Marco; Rutkowski, Stefan; Bognár, Laszlo; Cho, Byung-Kyu; Eberhart, Charles G; Conter, Cecile Faure; Fouladi, Maryam; French, Pim J; Grajkowska, Wieslawa A; Gupta, Nalin; Hauser, Peter; Jabado, Nada; Vasiljevic, Alexandre; Jung, Shin; Kim, Seung-Ki; Klekner, Almos; Kumabe, Toshihiro; Lach, Boleslaw; Leonard, Jeffrey R; Liau, Linda M; Massimi, Luca; Pollack, Ian F; Ra, Young Shin; Rubin, Joshua B; Van Meir, Erwin G; Wang, Kyu-Chang; Weiss, William A; Zitterbart, Karel; Bristow, Robert G; Alman, Benjamin; Hawkins, Cynthia E; Malkin, David; Clifford, Steven C; Pfister, Stefan M; Taylor, Michael D; Tabori, Uri
2014-12-24
TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
Wu, J R; Yeh, Y C
1975-05-01
Suppressors of gene 59-defective mutants were isolated by screening spontaneous, temperature-sensitive (ts) revertants of the amber mutant, amC5, in gene 59. Six ts revertants were isolated. No gene 59-defective ts recombinant was obtained by crossing each ts revertant with the wild type, T4D. However, suppressors of gene 59-defective mutants were obtained from two of these ts revertants. These suppressor mutants are referred to as dar (DNA arrested restoration). dar mutants specifically restored the abnormalities, both in DNA synthesis and burst size, caused by gene 59-defective mutants to normal levels. It is unlikely that dar mutants are nonsense suppressors since theý failed to suppress amber mutations in 11 other genes investigated. The genetic expression of dar is controlled by gene 55; therefore, dar is a late gene. The genetic location of dar has been mapped between genes 24 and 25, a region contiguous to late genes. dar appears to be another nonessential gene of T4 since burst sizes of dar were almost identical to those of the wild type. Mutations in dar did not affect genetic recombination and repair of UV-damaged DNA, but caused a sensitivity to hydroxyurea in progeny formation. The effect of the dar mutation on host DNA degradation cannot account for its hydroxyurea sensitivity. dar mutant alleles were recessive to the wild-type allele as judged by restoration of arrested DNA synthesis. The possible mechanisms for the suppression of defects in gene 59 are discussed.
Scarmeas, Nikolaos; Habeck, Christian G.; Zarahn, Eric; Anderson, Karen E.; Park, Aileen; Hilton, John; Pelton, Gregory H.; Tabert, Matthias H.; Honig, Lawrence S.; Moeller, James R.; Devanand, Davangere P.; Stern, Yaakov
2011-01-01
Although multivariate analytic techniques might identify diagnostic patterns that are not captured by univariate methods, they have rarely been used to study the neural correlates of Alzheimer's disease (AD) or cognitive impairment. Nonquantitative H215O PET scans were acquired during rest in 17 probable AD subjects selected for mild severity [mean-modified Mini Mental Status Examination (mMMS) 46/57; SD 5.1], 16 control subjects (mMMS 54; SD 2.5) and 23 subjects with minimal to mild cognitive impairment but no dementia (mMMS 53; SD 2.8). Expert clinical reading had low success in discriminating AD and controls. There were no significant mean flow differences among groups in traditional univariate SPM Voxel-wise analyses or region of interest (ROI) analyses. A covariance pattern was identified whose mean expression was significantly higher in the AD as compared to controls (P = 0.03; sensitivity 76–94%; specificity 63–81%). Sites of increased concomitant flow included insula, cuneus, pulvinar, lingual, fusiform, superior occipital and parahippocampal gyri, whereas decreased concomitant flow was found in cingulate, inferior parietal lobule, middle and inferior frontal, supramarginal and precentral gyri. The covariance analysis-derived pattern was then prospectively applied to the cognitively impaired subjects: as compared to subjects with Clinical Dementia Rating (CDR) = 0, subjects with CDR = 0.5 had significantly higher mean covariance pattern expression (P = 0.009). Expression of this pattern correlated inversely with Selective Reminding Test total recall (r = −0.401, P = 0.002), delayed recall (r = −0.351, P = 0.008) and mMMS scores (r = −0.401, P = 0.002) in all three groups combined. We conclude that patients with AD may differentially express resting cerebral blood flow covariance patterns even at very early disease stages. Significant alterations in expression of resting flow covariance patterns occur even for subjects with cognitive impairment. Expression of covariance patterns correlates with cognitive and functional performance measures, holding promise for meaningful associations with underlying biopathological processes. PMID:15325350
Requirements for the Military Message System (MMS) Family: Data Types and User Commands.
1986-04-11
AD-A167 126 REQUIREMENTS FOR THE MILITARY MESSASE SYSTEM (NHS) i FRILY: DATA TYPES AND USER CONNNDS(U) NAVAL RESEARCH LAB WASHINGTON DC C L HEITHEVER... System (MMS) Family: Data Types and User Commands CONSTANCE L. HEITMEYER Computer Science and Systems Branch I Information Technology Division April 11...Security Classification) Requirements for the Military Message System (MMS) Family: Data Types and User Commands 12. PERSONAL AUTHOR(S) Heitmeer, Constance
2014-10-30
A technician carefully removes the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
2014-10-30
Technicians begin to remove the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
MMS Spacecraft Uncrated & Moved
2014-10-29
Two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, the lower stack, mini-stack number 1, begin the trip from the Building 2 south encapsulation bay to the Building 1 high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
2014-10-30
Technicians prepare to remove the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
2014-10-30
Technicians have removed most of the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
MMS Spacecraft Uncrated & Moved
2014-10-29
Workers prepare a payload dolly for the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, during uncrating operations in the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
2014-10-30
Most of the protective covering has been removed from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, inside Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
MMS Spacecraft Uncrated & Moved
2014-10-29
Preparations are underway to remove the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, from their protective shipping container in the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
MMS Spacecraft Uncrated & Moved
2014-10-29
Preparations are underway to tow two of the observatories, the lower stack, mini-stack number 1, for NASA's Magnetospheric Multiscale Observatory, or MMS, from the Building 2 south encapsulation bay to the Building 1 high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
2014-10-30
Preparations are underway to remove the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
MMS Spacecraft Uncrated & Moved
2014-10-29
Two of the observatories, the lower stack, mini-stack number 1, for NASA's Magnetospheric Multiscale Observatory, or MMS, glides toward a payload dolly during uncrating operations in the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
MMS Spacecraft Uncrated & Moved
2014-10-29
Workers surround two of the observatories, the lower stack, mini-stack number 1, for NASA's Magnetospheric Multiscale Observatory, or MMS, on their trip from the Building 2 south encapsulation bay to the Building 1 high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
MMS Spacecraft Uncrated & Moved
2014-10-29
A crane is lowered toward the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, during uncrating operations in the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
MMS Spacecraft Uncrated & Moved
2014-10-29
The protective shipping container is lifted from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
2014-11-13
CAPE CANAVERAL, Fla. – Two Magnetospheric Multiscale, or MMS, spacecraft comprising the mission’s upper stack are towed between Buildings 1 and 2 of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the lower stack arrived at Astrotech on Oct. 29. The Magnetospheric Multiscale mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-10-30
A technician prepares to remove the protective covering from the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS, in Building 1 D high bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
Diago-Navarro, Elizabeth; Mora, Liliana; Buckingham, Richard H; Díaz-Orejas, Ramón; Lemonnier, Marc
2008-01-01
Novel mutations in prfA, the gene for the polypeptide release factor RF1 of Escherichia coli, were isolated using a positive genetic screen based on the parD (kis, kid) toxin–antitoxin system. This original approach allowed the direct selection of mutants with altered translational termination efficiency at UAG codons. The isolated prfA mutants displayed a ∼10-fold decrease in UAG termination efficiency with no significant changes in RF1 stability in vivo. All three mutations, G121S, G301S and R303H, were situated close to the nonsense codon recognition site in RF1:ribosome complexes. The prfA mutants displayed increased sensitivity to the RelE toxin encoded by the relBE system of E. coli, thus providing in vivo support for the functional interaction between RF1 and RelE. The prfA mutants also showed increased sensitivity to the Kid toxin. Since this toxin can cleave RNA in a ribosome-independent manner, this result was not anticipated and provided first evidence for the involvement of RF1 in the pathway of Kid toxicity. The sensitivity of the prfA mutants to RelE and Kid was restored to normal levels upon overproduction of the wild-type RF1 protein. We discuss these results and their utility for the design of novel antibacterial strategies in the light of the recently reported structure of ribosome-bound RF1. PMID:19019162
A detailed study of gerJ mutants of Bacillus subtilis.
Warburg, R J; Buchanan, C E; Parent, K; Halvorson, H O
1986-08-01
A total of nine gerJ mutants have now been isolated in Bacillus subtilis. All are defective in their spore germination properties, being blocked at an intermediate (phase grey) stage. The dormant spores are sensitive to heating at 90 degrees C and two of the mutants (generated by transposon insertion) produce spores sensitive at 80 degrees C. The spores of these two more extreme mutants had a visibly defective cortex when studied by electron microscopy, as did some of the other mutants. During sporulation, the acquisition of spore resistance properties and the appearance of the sporulation-specific penicillin-binding protein PBP5* were delayed. A strain probably carrying a lacZ fusion to the gerJ promoter demonstrated increased expression between t2 and t4. We propose that the gerJ locus is involved in the control of one or more sporulation-specific genes.
Jia, Yali; An, Lin; Wang, Ruikang K
2010-01-01
We demonstrate for the first time that the detailed blood flow distribution within intracranial dura mater and cortex can be visualized by an ultrahigh sensitive optical microangiography (UHS-OMAG). The study uses an UHS-OMAG system operating at 1310 nm with an imaging speed at 150 frames per second that requires approximately 10 s to complete one 3-D scan of approximately 2.5 x 2.5 mm(2). The system is sensitive to blood flow with a velocity ranging from approximately 4 microms to approximately 23 mms. We show superior performance of UHS-OMAG in providing functional images of capillary level microcirculation within meninges in mice with the cranium left intact, the results of which correlate well with the standard dural histopathology.
Isolation and analysis of a mammalian temperature-sensitive mutant defective in G2 functions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mineo, C.; Murakami, Y.; Ishimi, Y.
1986-11-01
A temperature-sensitive (ts) mutant, designated tsFT210, was isolated from a mouse mammary carcinoma cell line, FM3A. The tsFT210 cells grew normally at 33/sup 0/C (permissive temperature), but more than 80% of the cells were arrested at the G2 phase at 39/sup 0/C (non-permissive temperature) as revealed by flow-microfluorimetric analysis. DNA replication and synthesis of other macromolecules by this mutant seemed to be normal at 39/sup 0/C for at least 10h. However, in this mutant, hyperphosphorylation of H1 histone from the G2 to M phase, which occurs in the normal cell cycle, could not be detected at the non-permissive temperature. Thismore » suggests that a gene product which is temperature-sensitive in tsFT210 cells is necessary for hyperphosphorylation of H1 histone and that this gene product may be related to chromosome condensation.« less
Optimization of Dosing for EGFR-Mutant Non–Small Cell Lung Cancer with Evolutionary Cancer Modeling
Chmielecki, Juliann; Foo, Jasmine; Oxnard, Geoffrey R.; Hutchinson, Katherine; Ohashi, Kadoaki; Somwar, Romel; Wang, Lu; Amato, Katherine R.; Arcila, Maria; Sos, Martin L.; Socci, Nicholas D.; Viale, Agnes; de Stanchina, Elisa; Ginsberg, Michelle S.; Thomas, Roman K.; Kris, Mark G.; Inoue, Akira; Ladanyi, Marc; Miller, Vincent A.; Michor, Franziska; Pao, William
2012-01-01
Non–small cell lung cancers (NSCLCs) that harbor mutations within the epidermal growth factor receptor (EGFR) gene are sensitive to the tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. Unfortunately, all patients treated with these drugs will acquire resistance, most commonly as a result of a secondary mutation within EGFR (T790M). Because both drugs were developed to target wild-type EGFR, we hypothesized that current dosing schedules were not optimized for mutant EGFR or to prevent resistance. To investigate this further, we developed isogenic TKI-sensitive and TKI-resistant pairs of cell lines that mimic the behavior of human tumors. We determined that the drug-sensitive and drug-resistant EGFR-mutant cells exhibited differential growth kinetics, with the drug-resistant cells showing slower growth. We incorporated these data into evolutionary mathematical cancer models with constraints derived from clinical data sets. This modeling predicted alternative therapeutic strategies that could prolong the clinical benefit of TKIs against EGFR-mutant NSCLCs by delaying the development of resistance. PMID:21734175
Paraquat toxicity is increased in Escherichia coli defective in the synthesis of polyamines.
Minton, K W; Tabor, H; Tabor, C W
1990-04-01
We have shown that toxicity of paraquat for Escherichia coli is increased over 10-fold in strains defective in the biosynthesis of spermidine compared to isogenic strains containing spermidine. The increased sensitivity of these spermidine-deficient mutants to paraquat is eliminated by growth in medium containing spermidine or by endogenous supplementation of spermidine by the use of a speE+D+ plasmid. No paraquat toxicity is seen in the absence of oxygen, even in amine-deficient strains, indicating that superoxide is the agent responsible for the increased toxicity. However, the specific mechanisms responsible for the increased paraquat toxicity in the spermidine-deficient mutants remain to be determined. The marked sensitivity to paraquat of E. coli deficient in spermidine is of particular interest, since such mutants have no other phenotypic properties that can be easily assayed. This increased sensitivity has been used as the basis of a convenient method for scoring for mutants in polyamine biosynthesis and for the detection of plasmids containing the biosynthetic genes.
Chemotaxis-defective mutants of the nematode Caenorhabditis elegans.
Dusenbery, D B; Sheridan, R E; Russell, R L
1975-06-01
The technique of countercurrent separation has been used to isolate 17 independent chemotaxis-defective mutants of the nematode Caenorhabditis elegans. The mutants, selected to be relatively insensitive to the normally attractive salt NaCl, show varying degrees of residual sensitivity; some are actually weakly repelled by NaCl. The mutants are due to single gene defects, are autosomal and recessive, and identify at least five complementation groups.
Laser ablation-miniature mass spectrometer for elemental and isotopic analysis of rocks.
Sinha, M P; Neidholdt, E L; Hurowitz, J; Sturhahn, W; Beard, B; Hecht, M H
2011-09-01
A laser ablation-miniature mass spectrometer (LA-MMS) for the chemical and isotopic measurement of rocks and minerals is described. In the LA-MMS method, neutral atoms ablated by a pulsed laser are led into an electron impact ionization source, where they are ionized by a 70 eV electron beam. This results in a secondary ion pulse typically 10-100 μs wide, compared to the original 5-10 ns laser pulse duration. Ions of different masses are then spatially dispersed along the focal plane of the magnetic sector of the miniature mass spectrometer (MMS) and measured in parallel by a modified CCD array detector capable of detecting ions directly. Compared to conventional scanning techniques, simultaneous measurement of the ion pulse along the focal plane effectively offers a 100% duty cycle over a wide mass range. LA-MMS offers a more quantitative assessment of elemental composition than techniques that detect ions directly generated by the ablation process because the latter can be strongly influenced by matrix effects that vary with the structure and geometry of the surface, the wavelength of the laser beam, and the not well characterized ionization efficiencies of the elements in the process. The above problems attendant to the direct ion analysis has been minimized in the LA-MMS by analyzing the ablated neutral species after their post-ionization by electron impaction. These neutral species are much more abundant than the directly ablated ions in the ablated vapor plume and are, therefore, expected to be characteristic of the chemical composition of the solid. Also, the electron impact ionization of elements is well studied and their ionization cross sections are known and easy to find in databases. Currently, the LA-MMS limit of detection is 0.4 wt.%. Here we describe LA-MMS elemental composition measurements of various minerals including microcline, lepidolite, anorthoclase, and USGS BCR-2G samples. The measurements of high precision isotopic ratios including (41)K/(39)K (0.077 ± 0.004) and (29)Si/(28)Si (0.052 ± 0.006) in these minerals by LA-MMS are also described. The LA-MMS has been developed as a prototype instrument system for space applications for geochemical and geochronological measurements on the surface of extraterrestrial bodies. © 2011 American Institute of Physics
Toosizadeh, Nima; Bunting, Matthew; Howe, Carol; Mohler, Jane; Sprinkle, Jonathan; Najafi, Bijan
2014-01-01
Background Motorized mobility scooters (MMS) have become the most acceptable powered assistive device for those with impaired mobility, who have sufficient upper body strength and dexterity, and postural stability. Although several benefits have been attributed to MMS usage, there are likewise risks of use, including injuries and even deaths. Objective The aim of the current review was to summarize results from clinical studies regarding the enhancement of MMS driver safety with a primary focus on improving driving skills/performance using clinical approaches. We addressed three main objectives: 1) to identify and summarize any available evidence (strong, moderate, or weak evidence based on the quality of studies) regarding improved driving skills/performance following training/intervention; 2) to identify types of driving skills/performance that might be improved by training/intervention; and 3) to identify the use of technology in improving MMS performance or training procedure. Methods Articles were searched for in the following medical and engineering electronic databases: PubMed, Cochrane Library, Web of Science, ClinicalTrials.gov, PsycINFO, CINAHL, ERIC, EI Compendix, IEEE Explore, and REHABDATA. Inclusion criteria included: aging adults or those with ambulatory problems; intervention or targeted training; and clinical trial. Outcomes included: MMS skills/performance. Results Six articles met the inclusion criteria and are analyzed in this review. Four of the six articles contained training approaches for MMS drivers including skill trainings using real MMS inside and outside (i.e., in community) and in a 3D virtual environment. The other two studies contain infrastructural assessments (i.e., the minimum space required for safe maneuverability of MMS users) and additional mobility assistance tools to improve maneuverability and to enhance driving performance. Conclusions Results from the current review showed improved driving skills/performance by training, infrastructural assessments, and incorporating mobility assistance tools. MMS driving skills that can be improved through driver training include: weaving, negotiating with and avoiding pedestrian interference, simultaneous reading of signs and obstacle avoidance in path, level driving, forward and reverse driving, figure 8s, turning in place, crossing left slope, maneuvering down a 2-inch curb, and driving up and down inclines. However, several limitations exist in the available literature regarding evidence of improved driving skills/performance following training/intervention, such as small sample sizes, lack of control groups and statistical analysis. PMID:24481257
An alphavirus temperature-sensitive capsid mutant reveals stages of nucleocapsid assembly
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zheng, Yan, E-mail: yzheng15@students.kgi.edu; Kielian, Margaret, E-mail: margaret.kielian@einstein.yu.edu
2015-10-15
Alphaviruses have a nucleocapsid core composed of the RNA genome surrounded by an icosahedral lattice of capsid protein. An insertion after position 186 in the capsid protein produced a strongly temperature-sensitive growth phenotype. Even when the structural proteins were synthesized at the permissive temperature (28 °C), subsequent incubation of the cells at the non-permissive temperature (37 °C) dramatically decreased mutant capsid protein stability and particle assembly. Electron microscopy confirmed the presence of cytoplasmic nucleocapsids in mutant-infected cells cultured at the permissive temperature, but these nucleocapsids were not stable to sucrose gradient separation. In contrast, nucleocapsids isolated from mutant virus particlesmore » had similar stability to that of wildtype virus. Our data support a model in which cytoplasmic nucleocapsids go through a maturation step during packaging into virus particles. The insertion site lies in the interface between capsid proteins in the assembled nucleocapsid, suggesting the region where such a stabilizing transition occurs. - Highlights: • We characterize an alphavirus capsid insertion mutation. • These capsid mutants are highly temperature sensitive for growth. • The insertion affects nucleocapsid stability. • Results suggest that the nucleocapsid is stabilized during virus budding.« less
Wasser, Solomon P
2017-01-01
More than 130 medicinal functions are thought to be produced by medicinal mushrooms (MMs) and fungi, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, antihypercholesterolemic, antiviral, antibacterial, antiparasitic, antifungal, detoxification, hepatoprotective, antidiabetic, and other effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelia, and cultured broth. Special attention has been paid to mushroom polysaccharides. Numerous bioactive polysaccharides or polysaccharide-protein complexes from MMs seem to enhance innate and cell-mediated immune responses, and they exhibit antitumor activities in animals and humans. While the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds seems to be central. Most important for modern medicine are polysaccharides and low-molecular weight secondary metabolites with antitumor and immunostimulating properties. More than 600 studies have been conducted worldwide, and numerous human clinical trials on MMs have been published. Several of the mushroom compounds have proceeded through phase I, II, and III clinical studies and are used extensively and successfully in Asia to treat various cancers and other diseases. The aim of this review is to provide an overview of and analyze the literature on clinical trials using MMs with human anticancer, oncoimmunological, and immunomodulatory activities. High-quality, long-term, randomized, double-blind, placebo-controlled clinical studies of MMs, including well-sized population studies are definitely needed in order to yield statistical power showing their efficacy and safety. Clinical trials must obtain sufficient data on the efficacy and safety of MM-derived drugs and preparations. Discussion of results based on clinical studies of the anticancer, oncoimmunological, and immunomodulating activity of MMs are highlighted. Epidemiological studies with MMs are also discussed.
NASA Astrophysics Data System (ADS)
Pankratz, C. K.; Kokkonen, K.; Larsen, K. W.; Panneton, R. S.; Putnam, B.; Schafer, C.; Baker, D. N.; Burch, J. L.
2016-12-01
On September 1, 2015 the Magnetospheric MultiScale (MMS) constellation of four satellites completed their six-month commissioning period and began routine science data collection. Science operations for the mission is conducted at the Science Operations Center (SOC) at the Laboratory for Atmospheric and Space Physics, University of Colorado in Boulder, Colorado, USA. The MMS Science Data Center (SDC) is a component of the SOC responsible for the data production, management, dissemination, archiving, and visualization of the data from the extensive suite of 100 instruments onboard the four spacecraft. As of March 2016, MMS science data are openly available to the entire science community via the SDC. This includes hundreds of science parameters, and 50 gigabytes of data per day distributed across thousands of data files. Products are produced using integrated software systems developed and maintained by teams at other institutions using their own institutional software management procedures and made available via a centralized public web site and web services. To accomplish the data management, data processing, and system integration challenges present on this space mission, the MMS SDC incorporates a number of evolutionary techniques and technologies. This presentation will provide an informatics-oriented view of the MMS SDC, summarizing its technical aspects, novel technologies and data management practices that are employed, experiences with its design and development, and lessons learned. Also presented is the MMS "Scientist-in-the-Loop" (SITL) system, which is used to leverage human insight and expertise to optimize the data selected for transmission to the ground. This smoothly operating system entails the seamless interoperability of multiple mission facilities and data systems that ultimately translate scientist insight into uplink commands that triggers optimal data downlink to the ground.
NASA Astrophysics Data System (ADS)
Pankratz, Christopher; Kokkonen, Kim; Larsen, Kristopher; Panneton, Russell; Putnam, Brian; Schafer, Corey; Baker, Daniel; Burch, James
2016-04-01
On September 1, 2015 the Magnetospheric MultiScale (MMS) constellation of four satellites completed their six-month commissioning period and began routine science data collection. Science operations for the mission is conducted at the Science Operations Center (SOC) at the Laboratory for Atmospheric and Space Physics, University of Colorado in Boulder, Colorado, USA. The MMS Science Data Center (SDC) is a component of the SOC responsible for the data production, management, dissemination, archiving, and visualization of the data from the extensive suite of 100 instruments onboard the four spacecraft. As of March 2016, MMS science data are openly available to the entire science community via the SDC. This includes hundreds of science parameters, and 50 gigabytes of data per day distributed across thousands of data files. Products are produced using integrated software systems developed and maintained by teams at other institutions using their own institutional software management procedures and made available via a centralized public web site and web services. To accomplish the data management, data processing, and system integration challenges present on this space mission, the MMS SDC incorporates a number of evolutionary techniques and technologies. This presentation will provide an informatics-oriented view of the MMS SDC, summarizing its technical aspects, novel technologies and data management practices that are employed, experiences with its design and development, and lessons learned. Also presented is the MMS "Scientist-in-the-Loop" (SITL) system, which is used to leverage human insight and expertise to optimize the data selected for transmission to the ground. This smoothly operating system entails the seamless interoperability of multiple mission facilities and data systems that ultimately translate scientist insight into uplink commands that triggers optimal data downlink to the ground.
Benton, Michael G; Somasundaram, Swetha; Glasner, Jeremy D; Palecek, Sean P
2006-12-01
One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS) and gamma radiation. Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose responses varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes exhibiting biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1) are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The biphasic responses of these genes suggest that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response to gamma radiation all showed an increased induction with increasing gamma radiation dosage. Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing insights into how a cell deals with genotoxicity.
2015-01-12
Workers conduct a solar array illumination test on the upper stack of the Magnetospheric Multiscale spacecraft, or MMS, in the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. Illumination testing of the lower instrumentation payload stack was completed in December. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Kim Shiflett
2015-01-12
Workers conduct a solar array illumination test on the upper stack of the Magnetospheric Multiscale spacecraft, or MMS, in the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. Illumination testing of the lower instrumentation payload stack was completed in December. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Kim Shiflett
2015-01-12
A solar array illumination test is performed on the upper stack of the Magnetospheric Multiscale spacecraft, or MMS, in the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. Illumination testing of the lower instrumentation payload stack was completed in December. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Kim Shiflett
2015-01-12
A solar array illumination test is performed on the upper stack of the Magnetospheric Multiscale spacecraft, or MMS, in the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. Illumination testing of the lower instrumentation payload stack was completed in December. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Kim Shiflett
Light irradiation helps magnetotactic bacteria eliminate intracellular reactive oxygen species.
Li, Kefeng; Wang, Pingping; Chen, Chuanfang; Chen, Changyou; Li, Lulu; Song, Tao
2017-09-01
Magnetotactic bacteria (MTB) demonstrate photoresponse. However, little is known about the biological significance of this behaviour. Magnetosomes exhibit peroxidase-like activity and can scavenge reactive oxygen species (ROS). Magnetosomes extracted from the Magnetospirillum magneticum strain AMB-1 show enhanced peroxidase-like activity under illumination. The present study investigated the effects of light irradiation on nonmagnetic (without magnetosomes) and magnetic (with magnetosomes) AMB-1 cells. Results showed that light irradiation did not affect the growth of nonmagnetic and magnetic cells but significantly increased magnetosome synthesis and reduced intracellular ROS level in magnetic cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyse the expression level of magnetosome formation-associated genes (mamA, mms6, mms13 and mmsF) and stress-related genes (recA, oxyR, SOD, amb0664 and amb2684). Results showed that light irradiation upregulated the expression of mms6, mms13 and mmsF. Furthermore, light irradiation upregulated the expression of stress-related genes in nonmagnetic cells but downregulated them in magnetic cells. Additionally, magnetic cells exhibited stronger phototactic behaviour than nonmagnetic ones. These results suggested that light irradiation could heighten the ability of MTB to eliminate intracellular ROS and help them adapt to lighted environments. This phenomenon may be related to the enhanced peroxidase-like activity of magnetosomes under light irradiation. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.
Connolly, Karen L; Nehal, Kishwer S; Dusza, Stephen W; Rossi, Anthony M; Lee, Erica H
2016-09-01
Intraoperative pain during Mohs micrographic surgery (MMS) has not been characterized. However, many patients report postoperative pain on the day of MMS. We sought to determine if patients experience pain during their MMS visit. In phase I of this study, patients were asked to report intraoperative pain level using the verbal numerical rating scale (0-10) at discharge. In phase II, pain levels were assessed before each Mohs layer and at discharge, to determine whether pain was experienced throughout the day. Pain was reported at some point during the MMS day for 32.8% of patients (n = 98). The mean pain number reported was 3.7 (range 1-8) out of 10. Pain was more commonly reported by patients who spent a longer time in the office, had 3 or more Mohs layers, and had a flap or graft repair. Patients most frequently reported pain with surgical sites of the periorbital area and nose. Time between Mohs layers was not measured. There was nonstandardized use of intraoperative local anesthesia volume and oral pain medications. Some patients experience pain during MMS. However, the majority of patients report a low level of pain. Additional preventative measures could be considered in patients at higher risk. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Composite plasma polymerized sulfonated polystyrene membrane for PEMFC
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nath, Bhabesh Kumar; Khan, Aziz; Chutia, Joyanti, E-mail: jchutiaiasst@gmail.com
2015-10-15
Highlights: • Methyl methane sulfonate (MMS) is used as the sulfonating agent. • The proton conductivity of the membrane is found to be 0.141 S cm{sup −1}. • Power density of fuel cell with styrene/MMS membrane is 0.5 W cm{sup −2}. • The membrane exhibits thermal stability up to 140 °C. - Abstract: This work presents the introduction of an organic compound methyl methane sulfonate (MMS) for the first time in fabrication of polystyrene based proton exchange membrane (PEM) by plasma polymerization process. The membrane is fabricated by co-polymerizing styrene and MMS in capacitively coupled continuous RF plasma. The chemicalmore » composition of the plasma polymerized polymer membrane is investigated using Fourier Transform Infrared Spectroscopy which reveals the formation of composite structure of styrene and MMS. The surface morphology studied using AFM and SEM depicts the effect of higher partial pressure of MMS on surface topography of the membrane. The proton transport property of the membrane studied using electrochemical impedance spectroscopy shows the achievement of maximum proton conductivity of 0.141 S cm{sup −1} which is comparable to Nafion 117 membrane. Fuel cell performance test of the synthesized membrane shows a maximum power density of 500 mW cm{sup −2} and current density of 0.62 A cm{sup −2} at 0.6 V.« less
Princz, Lissa N; Wild, Philipp; Bittmann, Julia; Aguado, F Javier; Blanco, Miguel G; Matos, Joao; Pfander, Boris
2017-03-01
DNA repair by homologous recombination is under stringent cell cycle control. This includes the last step of the reaction, disentanglement of DNA joint molecules (JMs). Previous work has established that JM resolving nucleases are activated specifically at the onset of mitosis. In case of budding yeast Mus81-Mms4, this cell cycle stage-specific activation is known to depend on phosphorylation by CDK and Cdc5 kinases. Here, we show that a third cell cycle kinase, Cdc7-Dbf4 (DDK), targets Mus81-Mms4 in conjunction with Cdc5-both kinases bind to as well as phosphorylate Mus81-Mms4 in an interdependent manner. Moreover, DDK-mediated phosphorylation of Mms4 is strictly required for Mus81 activation in mitosis, establishing DDK as a novel regulator of homologous recombination. The scaffold protein Rtt107, which binds the Mus81-Mms4 complex, interacts with Cdc7 and thereby targets DDK and Cdc5 to the complex enabling full Mus81 activation. Therefore, Mus81 activation in mitosis involves at least three cell cycle kinases, CDK, Cdc5 and DDK Furthermore, tethering of the kinases in a stable complex with Mus81 is critical for efficient JM resolution. © 2017 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
Object Detection from MMS Imagery Using Deep Learning for Generation of Road Orthophotos
NASA Astrophysics Data System (ADS)
Li, Y.; Sakamoto, M.; Shinohara, T.; Satoh, T.
2018-05-01
In recent years, extensive research has been conducted to automatically generate high-accuracy and high-precision road orthophotos using images and laser point cloud data acquired from a mobile mapping system (MMS). However, it is necessary to mask out non-road objects such as vehicles, bicycles, pedestrians and their shadows in MMS images in order to eliminate erroneous textures from the road orthophoto. Hence, we proposed a novel vehicle and its shadow detection model based on Faster R-CNN for automatically and accurately detecting the regions of vehicles and their shadows from MMS images. The experimental results show that the maximum recall of the proposed model was high - 0.963 (intersection-over-union > 0.7) - and the model could identify the regions of vehicles and their shadows accurately and robustly from MMS images, even when they contain varied vehicles, different shadow directions, and partial occlusions. Furthermore, it was confirmed that the quality of road orthophoto generated using vehicle and its shadow masks was significantly improved as compared to those generated using no masks or using vehicle masks only.
In-Flight Calibration Processes for the MMS Fluxgate Magnetometers
NASA Technical Reports Server (NTRS)
Bromund, K. R.; Leinweber, H. K.; Plaschke, F.; Strangeway, R. J.; Magnes, W.; Fischer, D.; Nakamura, R.; Anderson, B. J.; Russell, C. T.; Baumjohann, W.;
2015-01-01
The calibration effort for the Magnetospheric Multiscale Mission (MMS) Analog Fluxgate (AFG) and DigitalFluxgate (DFG) magnetometers is a coordinated effort between three primary institutions: University of California, LosAngeles (UCLA); Space Research Institute, Graz, Austria (IWF); and Goddard Space Flight Center (GSFC). Since thesuccessful deployment of all 8 magnetometers on 17 March 2015, the effort to confirm and update the groundcalibrations has been underway during the MMS commissioning phase. The in-flight calibration processes evaluatetwelve parameters that determine the alignment, orthogonalization, offsets, and gains for all 8 magnetometers usingalgorithms originally developed by UCLA and the Technical University of Braunschweig and tailored to MMS by IWF,UCLA, and GSFC. We focus on the processes run at GSFC to determine the eight parameters associated with spin tonesand harmonics. We will also discuss the processing flow and interchange of parameters between GSFC, IWF, and UCLA.IWF determines the low range spin axis offsets using the Electron Drift Instrument (EDI). UCLA determines the absolutegains and sensor azimuth orientation using Earth field comparisons. We evaluate the performance achieved for MMS andgive examples of the quality of the resulting calibrations.
Solar microwave millisecond spike at 2.84 GHz
NASA Technical Reports Server (NTRS)
Fu, Qi-Jun; Jin, Sheng-Zhen; Zhao, Ren-Yang; Zheng, Le-Ping; Liu, Yu-Ying; Li, Xiao-Cong; Wang, Shu-Lan; Chen, Zhi-Jun; Hu, Chu-Min
1986-01-01
Using the high time resolution of 1 ms, the data of solar microwave millisecond spike (MMS) event was recorded more than two hundred times at the frequency of 2.84 GHz at Beijing (Peking) Observatory since May 1981. A preliminary analysis was made. It can be seen from the data that the MMS-events have a variety of the fast activities such as the dispersed and isolated spikes, the clusters of the crowded spikes, the weak spikes superimposed on the noise background, and the phenomena of absorption. The marked differences from that observed with lower time resolution are presented. Using the data, a valuable statistical analysis was made. There are close correlations between MMS-events and hard X-ray bursts, and fast drifting bursts. The MMS events are highly dependent on the type of active regions and the magnetic field configuration. It seems to be crucial to find out the accurate positions on the active region where the MMS-events happen and to make co-operative observations at different bands during the special period when specific active regions appear on the solar disk.
SCC of Alloy 690 and its Weld Metals
NASA Astrophysics Data System (ADS)
Andresen, Peter L.; Morra, Martin M.; Ahluwalia, Kawaljit
Alloy 690 base metal, HAZ and weld metal were tested in representative PWR primary water at 290 to 360°C. Intergranular cracking was observed in all materials. Growth rates as high as 1.2 × 10-6 mm/s were observed in the S-L orientation with micro structural banded material after cold rolling or forging to align the planes of banding, rolling and cracking. However, not all banded material has exhibited such high growth rates. Growth rates on homogeneous Alloy 690, including extruded CRDM tubing, often showed growth rates in the range of 2 - 8 × 10-8 mm/s in cold worked condition and an S-L orientation. Crack growth rates in some Alloy 690 tests were in the range of 1 to 10 × 10-9 mm/s, primarily in orientations other than S-L. For cracks aligned along the HAZ, growth rates as high as 1.2 × 10-8 mm/s were observed. Alloy 152/52/52i weld metals always exhibited low growth rates, apart from a weld that was further cold worked by 20%, which grew at 7 × 10-9 mm/s.
Launch Window Analysis for the Magnetospheric Multiscale Mission
NASA Technical Reports Server (NTRS)
Williams, Trevor W.
2012-01-01
The NASA Magnetospheric Multiscale (MMS) mission will fly four spinning spacecraft in formation in highly elliptical orbits to study the magnetosphere of the Earth. This paper describes the development of an MMS launch window tool that uses the orbitaveraged Variation of Parameter equations as the basis for a semi-analytic quantification of the dominant oblateness and lunisolar perturbation effects on the MMS orbit. This approach, coupled with a geometric interpretation of all of the MMS science and engineering constraints, allows a scan of 180(sup 2) = 32,400 different (RAAN, AOP) pairs to be carried out for a specified launch day in less than 10 s on a typical modern laptop. The resulting plot indicates the regions in (RAAN, AOP) space where each constraint is satisfied or violated: their intersection gives, in an easily interpreted graphical manner, the final solution space for the day considered. This tool, SWM76, is now used to provide launch conditions to the full fidelity (but far slower) MMS simulation code: very good agreement has been observed between the two methods.
Electrodynamic Context of Magnetopause Dynamics Observed by Magnetospheric Multiscale
NASA Technical Reports Server (NTRS)
Anderson, Brian J.; Russell, Christopher T.; Strangeway, Robert J.; Plaschke, Ferdinand; Magnes, Werner; Fischer, David; Korth, Haje; Merkin, Viacheslav G.; Barnes, Robin J.; Waters, Colin L.;
2016-01-01
Magnetopause observations by Magnetospheric Multiscale (MMS) and Birkeland currents observed by the Active Magnetosphere and Planetary Electrodynamics Response Experiment are used to relate magnetopause encounters to ionospheric electrodynamics. MMS magnetopause crossings on 15 August and 19 September 2015 occurred earthward of expectations due to solar wind ram pressure alone and coincided with equatorward expansion of the Birkeland currents. Magnetopause erosion, consistent with expansion of the polar cap, contributed to the magnetopause crossings. The ionospheric projections of MMS during the events and at times of the magnetopause crossings indicate that MMS observations are related to the main path of flux transport in one case but not in a second. The analysis provides a way to routinely relate in situ observations to the context of in situ convection and flux transport.
The Electron Drift Instrument for MMS
NASA Astrophysics Data System (ADS)
Torbert, R. B.; Vaith, H.; Granoff, M.; Widholm, M.; Gaidos, J. A.; Briggs, B. H.; Dors, I. G.; Chutter, M. W.; Macri, J.; Argall, M.; Bodet, D.; Needell, J.; Steller, M. B.; Baumjohann, W.; Nakamura, R.; Plaschke, F.; Ottacher, H.; Hasiba, J.; Hofmann, K.; Kletzing, C. A.; Bounds, S. R.; Dvorsky, R. T.; Sigsbee, K.; Kooi, V.
2016-03-01
The Electron Drift Instrument (EDI) on the Magnetospheric Multiscale (MMS) mission measures the in-situ electric and magnetic fields using the drift of a weak beam of test electrons that, when emitted in certain directions, return to the spacecraft after one or more gyrations. This drift is related to the electric field and, to a lesser extent, the gradient in the magnetic field. Although these two quantities can be determined separately by use of different electron energies, for MMS regions of interest the magnetic field gradient contribution is negligible. As a by-product of the drift determination, the magnetic field strength and constraints on its direction are also determined. The present paper describes the scientific objectives, the experimental method, and the technical realization of the various elements of the instrument on MMS.
2014-11-13
CAPE CANAVERAL, Fla. – Two Magnetospheric Multiscale, or MMS, spacecraft, comprising the mission's upper stack, come into view as the shipping container is removed in Building 2 of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the lower stack arrived at Astrotech on Oct. 29. The Magnetospheric Multiscale mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-11-13
CAPE CANAVERAL, Fla. – Two Magnetospheric Multiscale, or MMS, spacecraft comprising the mission’s upper stack, at left, arrive in the Building 1 high bay of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the lower stack, at right, arrived at Astrotech on Oct. 29. The Magnetospheric Multiscale mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-11-13
CAPE CANAVERAL, Fla. – Two Magnetospheric Multiscale, or MMS, spacecraft comprising the mission’s upper stack arrive in the Building 1 airlock of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the lower stack, in the high bay uat right, arrived at Astrotech on Oct. 29. The Magnetospheric Multiscale mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-11-13
CAPE CANAVERAL, Fla. – Two Magnetospheric Multiscale, or MMS, spacecraft comprising the mission’s upper stack are transported to the airlock of Building 1 of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the lower stack arrived at Astrotech on Oct. 29. The Magnetospheric Multiscale mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-11-13
CAPE CANAVERAL, Fla. – The protective shipping container is removed from around the upper stack of the Magnetospheric Multiscale, or MMS, spacecraft in Building 2 of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the lower stack arrived at Astrotech on Oct. 29. The Magnetospheric Multiscale mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-11-13
CAPE CANAVERAL, Fla. – Two Magnetospheric Multiscale , or MMS, spacecraft comprising the mission’s upper stack are lowered onto a payload dolly in Building 2 of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the lower stack arrived at Astrotech on Oct. 29. The Magnetospheric Multiscale mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
Magnetospheric Multiscale (MMS)
2014-05-09
Observatory #1 is shown here on the Ransome table, tilted in a vertical position to provide better access for the engineers and technicians. Learn more about MMS at www.nasa.gov/mms Credit NASA/Goddard The Magnetospheric Multiscale, or MMS, will study how the sun and the Earth's magnetic fields connect and disconnect, an explosive process that can accelerate particles through space to nearly the speed of light. This process is called magnetic reconnection and can occur throughout all space. 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
MMS Spacecraft Uncrated & Moved
2014-10-29
Workers attach a crane to the protective shipping container to prepare to uncover the lower stack, mini-stack number 1, two of the observatories for NASA's Magnetospheric Multiscale Observatory, or MMS. They were delivered to the Building 2 south encapsulation bay at the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The MMS upper stack, mini-stack number 2, is scheduled to arrive in about two weeks. MMS is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015.
2014-11-13
CAPE CANAVERAL, Fla. – Two Magnetospheric Multiscale, or MMS, spacecraft comprising the mission’s upper stack are lifted from the transporter in Building 2 of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the lower stack arrived at Astrotech on Oct. 29. The Magnetospheric Multiscale mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-11-13
CAPE CANAVERAL, Fla. – Two Magnetospheric Multiscale, or MMS, spacecraft comprising the mission’s upper stack are towed from Building 2 to the Building 1 high bay of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the lower stack arrived at Astrotech on Oct. 29. The Magnetospheric Multiscale mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
2014-11-13
CAPE CANAVERAL, Fla. – The protective covering is removed from the two Magnetospheric Multiscale, or MMS, spacecraft comprising the mission’s upper stack in the Building 1 high bay of the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. The two MMS spacecraft comprising the lower stack arrived at Astrotech on Oct. 29. The Magnetospheric Multiscale mission is a Solar Terrestrial Probes mission comprising four identically instrumented spacecraft that will use Earth’s magnetosphere as a laboratory to study the microphysics of three fundamental plasma processes: magnetic reconnection, energetic particle acceleration and turbulence. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12, 2015. To learn more about MMS, visit http://mms.gsfc.nasa.gov. Photo credit: NASA/Kim Shiflett
Zhu, Jufen; Yu, Xinxu; Xie, Baogui; Gu, Xiaokui; Zhang, Zhenying; Li, Shaojie
2013-06-01
To gain insight into the regulatory mechanisms of oxidative stress responses in filamentous fungi, the genome-wide transcriptional response of Neurospora crassa to menadione was analysed by digital gene expression (DGE) profiling, which identified 779 upregulated genes and 576 downregulated genes. Knockout mutants affecting 130 highly-upregulated genes were tested for menadione sensitivity, which revealed that loss of the transcription factor siderophore regulation (SRE) (a transcriptional repressor for siderophore biosynthesis), catatase-3, cytochrome c peroxidase or superoxide dismutase 1 copper chaperone causes hypersensitivity to menadione. Deletion of sre dramatically increased transcription of the siderophore biosynthesis gene ono and the siderophore iron transporter gene sit during menadione stress, suggesting that SRE is required for repression of iron uptake under oxidative stress conditions. Contrary to its phenotype, the sre deletion mutant showed higher transcriptional levels of genes encoding reactive oxygen species (ROS) scavengers than wild type during menadione stress, which implies that the mutant suffers a higher level of oxidative stress than wild type. Uncontrolled iron uptake in the sre mutant might exacerbate cellular oxidative stress. This is the first report of a negative regulator of iron assimilation participating in the fungal oxidative stress response. In addition to SRE, eight other transcription factor genes were also menadione-responsive but their single gene knockout mutants showed wild-type menadione sensitivity. Two of them, named as mit-2 (menadione induced transcription factor-2) and mit-4 (menadione induced transcription factor-4), were selected for double mutant analysis. The double mutant was hypersensitive to menadione. Similarly, the double mutation of mit-2 and sre also had additive effects on menadione sensitivity, suggesting multiple transcription factors mediate oxidative stress resistance in an additive manner. Copyright © 2013 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.
2015-02-07
A solid rocket motor for the United Launch Alliance Atlas V rocket slated to boost NASA's Magnetospheric Multiscale mission, or MMS, is lowered into position inside the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. Four identical MMS spacecraft will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. Launch is set for March 12. To learn more: http://www.nasa.gov/mms. Photo credit: NASA/ Kim Shiflett
2015-02-07
A solid rocket motor for the United Launch Alliance Atlas V rocket slated to boost NASA's Magnetospheric Multiscale mission, or MMS, is lowered into position inside the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. Four identical MMS spacecraft will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. Launch is set for March 12. To learn more: http://www.nasa.gov/mms. Photo credit: NASA/ Kim Shiflett
2015-02-07
A solid rocket motor for the United Launch Alliance Atlas V rocket slated to boost NASA's Magnetospheric Multiscale mission, or MMS, is lifted at the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. Four identical MMS spacecraft will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. Launch is set for March 12. To learn more: http://www.nasa.gov/mms. Photo credit: NASA/ Kim Shiflett
2015-02-07
A solid rocket motor for the United Launch Alliance Atlas V rocket slated to boost NASA's Magnetospheric Multiscale mission, or MMS, is lowered into position inside the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. Four identical MMS spacecraft will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. Launch is set for March 12. To learn more: http://www.nasa.gov/mms. Photo credit: NASA/ Kim Shiflett
2015-02-07
A solid rocket motor for the United Launch Alliance Atlas V rocket slated to boost NASA's Magnetospheric Multiscale mission, or MMS, arrives at the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. Four identical MMS spacecraft will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. Launch is set for March 12. To learn more: http://www.nasa.gov/mms. Photo credit: NASA/ Kim Shiflett
2015-02-07
A solid rocket motor for the United Launch Alliance Atlas V rocket slated to boost NASA's Magnetospheric Multiscale mission, or MMS, is lowered into position inside the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. Four identical MMS spacecraft will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. Launch is set for March 12. To learn more: http://www.nasa.gov/mms. Photo credit: NASA/ Kim Shiflett
2015-02-07
A solid rocket motor for the United Launch Alliance Atlas V rocket slated to boost NASA's Magnetospheric Multiscale mission, or MMS, is lifted at the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. Four identical MMS spacecraft will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. Launch is set for March 12. To learn more: http://www.nasa.gov/mms. Photo credit: NASA/ Kim Shiflett
2015-02-07
A solid rocket motor for the United Launch Alliance Atlas V rocket slated to boost NASA's Magnetospheric Multiscale mission, or MMS, is lifted at the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. Four identical MMS spacecraft will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. Launch is set for March 12. To learn more: http://www.nasa.gov/mms. Photo credit: NASA/ Kim Shiflett
2015-02-07
A solid rocket motor for the United Launch Alliance Atlas V rocket slated to boost NASA's Magnetospheric Multiscale mission, or MMS, arrives at the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. Four identical MMS spacecraft will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. Launch is set for March 12. To learn more: http://www.nasa.gov/mms. Photo credit: NASA/ Kim Shiflett
2015-02-07
A solid rocket motor for the United Launch Alliance Atlas V rocket slated to boost NASA's Magnetospheric Multiscale mission, or MMS, arrives at the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. Four identical MMS spacecraft will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. Launch is set for March 12. To learn more: http://www.nasa.gov/mms. Photo credit: NASA/ Kim Shiflett
2015-02-07
A solid rocket motor for the United Launch Alliance Atlas V rocket slated to boost NASA's Magnetospheric Multiscale mission, or MMS, is lowered into position inside the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. Four identical MMS spacecraft will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. Launch is set for March 12. To learn more: http://www.nasa.gov/mms. Photo credit: NASA/ Kim Shiflett
2015-02-07
A solid rocket motor for the United Launch Alliance Atlas V rocket slated to boost NASA's Magnetospheric Multiscale mission, or MMS, is lifted at the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. Four identical MMS spacecraft will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. Launch is set for March 12. To learn more: http://www.nasa.gov/mms. Photo credit: NASA/ Kim Shiflett
2015-02-07
A solid rocket motor for the United Launch Alliance Atlas V rocket slated to boost NASA's Magnetospheric Multiscale mission, or MMS, is lifted at the mobile service tower at Space Launch Complex 41 on Cape Canaveral Air Force Station in Florida. Four identical MMS spacecraft will study the mystery of how magnetic fields around Earth connect and disconnect, explosively releasing energy via a process known a magnetic reconnection. Launch is set for March 12. To learn more: http://www.nasa.gov/mms. Photo credit: NASA/ Kim Shiflett
2015-01-12
Preparations are underway for illumination testing of the solar panels on the upper stack of the Magnetospheric Multiscale spacecraft, or MMS, in the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. Illumination testing of the lower instrumentation payload stack was completed in December. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Kim Shiflett
Ando, Akira; Tanaka, Fumiko; Murata, Yoshinori; Takagi, Hiroshi; Shima, Jun
2006-03-01
Yeasts used in bread making are exposed to high concentrations of sucrose during sweet dough fermentation. Despite its importance, tolerance to high-sucrose stress is poorly understood at the gene level. To clarify the genes required for tolerance to high-sucrose stress, genome-wide screening was undertaken using the complete deletion strain collection of diploid Saccharomyces cerevisiae. The screening identified 273 deletions that yielded high sucrose sensitivity, approximately 20 of which were previously uncharacterized. These 273 deleted genes were classified based on their cellular function and localization of their gene products. Cross-sensitivity of the high-sucrose-sensitive mutants to high concentrations of NaCl and sorbitol was studied. Among the 273 sucrose-sensitive deletion mutants, 269 showed cross-sensitivities to sorbitol or NaCl, and four (i.e. ade5,7, ade6, ade8, and pde2) were specifically sensitive to high sucrose. The general stress response pathways via high-osmolarity glycerol and stress response element pathways and the function of the invertase in the ade mutants were similar to those in the wild-type strain. In the presence of high-sucrose stress, intracellular contents of ATP in ade mutants were at least twofold lower than that of the wild-type cells, suggesting that depletion of ATP is a factor in sensitivity to high-sucrose stress. The genes identified in this study might be important for tolerance to high-sucrose stress, and therefore should be target genes in future research into molecular modification for breeding of yeast tolerant to high-sucrose stress.
An improved Abbott ARCHITECT assay for the detection of hepatitis B virus surface antigen (HBsAg).
Lou, Sheng C; Pearce, Sandra K; Lukaszewska, Teresa X; Taylor, Russell E; Williams, Gregg T; Leary, Thomas P
2011-05-01
The sensitive and accurate detection of hepatitis B virus surface antigen (HBsAg) is critical to the identification of infection and the prevention of transfusion transmitted disease. Improvement in HBsAg assay sensitivity is essential to reduce the window to detect an acute HBV infection. Additionally, the sensitive detection of HBsAg mutants that continue to evolve due to vaccine escape, immune selection and an error prone reverse transcriptase is a necessity. A fully automated HBsAg prototype assay on the Abbott ARCHITECT instrument was developed to improve sensitivity and mutant detection. This magnetic microparticle-based assay utilizes anti-HBsAg monoclonal antibodies to capture antigen present in serum or plasma. Captured antigen is then detected using anti-HBsAg antibody conjugated with the chemiluminescent compound, acridinium. The sensitivity of the ARCHITECT HBsAg prototype assay was improved as compared to the current ARCHITECT, PRISM, and competitor HBsAg assays. The enhancement in assay sensitivity was demonstrated by the use of commercially available HBV seroconversion panels. The prototype assay detected more panel members (185 of 383) vs. the current ARCHITECT (171), PRISM (181), or competitor HBsAg assays (73/140 vs. 62/140, respectively). The ARCHITECT prototype assay also efficiently detected all mutants evaluated. Finally, the sensitivity improvement did not compromise the specificity of the assay (99.94%). An improved Abbott ARCHITECT HBsAg prototype assay with enhanced detection of HBsAg and HBsAg mutants, as well as equivalent specificity was developed for the detection, diagnosis, and management of HBV infection. Copyright © 2011 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Müller, C. S.; Auerbach, H.; Stegmaier, K.; Wolny, J. A.; Schünemann, V.; Pierik, A. J.
2017-11-01
The Thermus thermophilus Rieske protein ( TtRP) contains a 2Fe-2S cluster with one iron (Fe-Cys) coordinated by four sulfur atoms (2xS2- and 2xCys) and one iron (Fe-His) by two sulfur and two nitrogen atoms (2xS2-, His134 and His154). Here, the protein is investigated at three pH values (6.0, 8.5 and 10.5) in order to elucidate the protonation states of the His-ligands. Examination of the effect of protonation on the electronic structure of the cluster via Mössbauer spectroscopy gives a deeper understanding of the coupling of electron transfer to the protonation state of the His-ligands. Two components (1 referring to Fe-Cys and 2 to Fe-His) with parameters typical for a diamagnetic [2Fe-2S]2+ cluster are detected. The Mössbauer parameters and the protonation state clearly correlate: while δ remains almost pH-independent with δ 1 (pH6.0) = 0.23 (± 0.01) mms- 1 and δ 1 (pH10.5) = 0.24 (± 0.01) mms- 1 for Fe-Cys, it decreases for Fe-His from δ 2 (pH6.0) = 0.34 (± 0.01) mms- 1 to δ 2 (pH10.5) = 0.28 (± 0.01) mms- 1. Δ E Q changes from Δ E Q1 (pH6.0) = 0.57 (± 0.01) mms- 1 to Δ E Q1 (pH10.5) = 0.45 (± 0.01) mms- 1 and from Δ E Q2 (pH6.0) = 1.05 (± 0.01) mms- 1 to Δ E Q2 (pH10.5) = 0.71 (± 0.01) mms- 1. Density functional theory (DFT)-calculations based on the crystal structure (pdb 1NYK) (Hunsicker-Wang et al. Biochemistry 42, 7303, 2003) have been performed for the Rieske-cluster with different His-ligand protonation states, reproducing the experimentally observed trend.
Growth rate and malignant potential of small gallbladder polyps--systematic review of evidence.
Wiles, Rebecca; Varadpande, Mandar; Muly, Sudha; Webb, Jolanta
2014-08-01
The overall aim of this systematic review was to determine whether ultrasound (US) follow up for gallbladder polyps (GBPs) measuring less than 10 mms is necessary. A search was performed in MEDLINE and EMBASE between January 1976 and January 2012 using keywords: gallbladder, polyps, neoplasm, cancer, tumour, carcinoma, malignant, adenoma. Included were studies involving adult patients, examined with transabdominal US at least twice. The outcomes of included studies were gallbladder polyp growth as demonstrated on US over time, followed where available by histological examination of cholecystectomy specimens. Ten studies met the inclusion criteria for the review. Altogether 1958 subjects with mean age between 41.5 and 59 years were followed up with US. The percentage of GBPs which showed growth over the follow up period ranged from 1% to 23%. 43 neoplastic polyps were found in total irrespective of size, 20 of which were malignant and at least 7 of those were >10 mms. At least 7 malignancies were present in polyps <10 mms but it was unknown if they had undergone growth on follow up. Level II-2 and below evidence on rate of growth of small GBPs <10 mms exists in the literature. It indicates that growth does occur in a significant minority of small GBPs, but it is slow. Due to deficient reporting and small numbers of cases, the correlation between growth of GBP and development of malignancy cannot be established using currently available evidence. Malignancy can be present in polyps <10 mms although it is significantly more frequent in polyps >10 mms. Cholecystectomy for symptomatic GBPs irrespective of their size, alongside the current practice for removal of gall bladders containing asymptomatic polyps >10 mms, is proposed. No evidence based US follow up schedule can be recommended at present for asymptomatic polyps <10 mms, and in its absence an intuitive follow up with US is likely to continue. Copyright © 2014 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.
Multimedia Messaging Service teleradiology in the provision of emergency neurosurgery services.
Ng, Wai Hoe; Wang, Ernest; Ng, Ivan
2007-04-01
Neurosurgical emergencies constitute a significant proportion of workload of a tertiary neurosurgical service. Prompt diagnosis and emergent institution of definitive treatment are critical to reduce neurological mortality and morbidity. Diagnosis is highly dependent on accurate interpretation of scans by experienced clinicians. This expertise may not be readily available especially after office hours because many neurosurgical units are manned by middle-level neurosurgical staff with varying levels of experience in scan interpretation. Multimedia Messaging Service mobile phone technology offers a simple, cheap, quick, and effective solution to the problem of scan interpretation. An MMS takes only a few minutes to send and receive and allows senior doctors to view important images and make important clinical decisions to enhance patient management in an emergency situation. A mobile phone (with VGA camera and MMS capabilities) was provided to the neurosurgery registrar on call. The on-call mobile phone is passed on to the corresponding registrar on-call the next day. All consultants had personal mobile phones that are MMS-enabled. Relevant representative CT/MRI images can be taken directly from the mobile phone from the PACS off the computer screen. When only hard copies are available, the images can be taken off the light box. After a 12-month trial period, a questionnaire was given to all staff involved in the project to ascertain the usefulness of the MMS teleradiology service. The survey on the use of the MMS service in a tertiary neurosurgical service demonstrated that the technology significantly improved the level of confidence of the senior-level staff in emergent clinical decision making. Significantly, the MMS images were of sufficient quality and resolution to obviate the need to view the actual scans. The impact of MMS is less pronounced in the middle-level staff, but there was a trend that most of the junior staff found the service more useful. The MMS technology is demonstrated to be a useful media for the transmission of high-quality images to assist in the diagnostic process and implementation of emergent clinical therapy. It is already in widespread use and can be seamlessly and rapidly implemented in the clinical arena to improve the quality of patient care.
Patalay, Praveetha; Deighton, Jessica; Fonagy, Peter; Vostanis, Panos; Wolpert, Miranda
2014-01-01
The Me and My School Questionnaire (M&MS) is a self-report measure for children aged eight years and above that measures emotional difficulties and behavioural difficulties, and has been previously validated in a community sample. The present study aimed to assess its clinical sensitivity to justify its utility as a screening tool in schools. Data were collected from service-users (n = 91, 8-15 years) and accompanying parent/carer in outpatient mental health services in England. A matched community sample (N = 91) were used to assess the measure's ability to discriminate between low- and high-risk samples. Receiver operating curves (area under the curve, emotional difficulties = .79; behavioural difficulties = .78), mean comparisons (effect size, emotional difficulties d = 1.17, behavioural difficulties = 1.12) and proportions above clinical thresholds indicate that the measure satisfactorily discriminates between the samples. The scales have good internal reliability (emotional difficulties α = .84; behavioural difficulties α = .82) and cross-informant agreement with parent-reported symptoms is comparable to existing measures (r = .30). The findings of this study indicate that the M&MS sufficiently discriminates between high-risk (clinic) and low-risk (community) samples, has good internal reliability, compares favourably with existing self-report measures of mental health and has comparable levels of agreement between parent-report and self-report to other measures. Alongside existing validation of the M&MS, these findings justify the measures use as a self-report screening tool for mental health problems in community settings for children aged as young as 8 years.
Wan, Xiao-Meng; Zhang, Mu; Zhang, Pei; Xie, Zhi-Shen; Xu, Feng-Guo; Zhou, Ping; Ma, Shi-Ping; Xu, Xiao-Jun
2016-11-01
Menopausal metabolic syndrome (MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases (CVD) and type II diabetes mellitus (T2DM). Erzhiwan (EZW), composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan (JE). The present study was designed to determine the anti-MMS effects of JE using ovariectomized (OVX) adult female rats that were treated with JE for 4 weeks, and β-tc-6 cells and INS cells were used to detected the protect effectiveness of JE. Our results showed JE could increase insulin sensitivity and ameliorated hyperlipidemia. Metabolomics analysis showed that the serum levels of branched and aromatic amino acids were down-regulated in serum by JE administration. Moreover, JE enhanced the function of islet β cells INS-1 and β-tc-6, through increasing the glucose stimulated insulin secretion (GSIS), which was abolished by estrogen receptor (ER) antagonist, indicating that JE functions were mediated by ER signaling. Additionally, JE did not induce tumorigenesis in rat mammary tissue or promoted proliferation of MCF-7 and Hela cells. In conclusion, our work demonstrated that JE ameliorated OVX-induced glucose and lipid metabolism disorder through activating estrogen receptor pathway and promoting GSIS in islet β cells, thus indicating that JE could be a safe and effective medication for MMS therapy. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
Xu, Lisen; Knox, Wayne H; DeMagistris, Margaret; Wang, Nadan; Huxlin, Krystel R
2011-10-17
To test the feasibility of intratissue refractive index shaping (IRIS) in living corneas by using 400-nm femtosecond (fs) laser pulses (blue-IRIS). To test the hypothesis that the intrinsic two-photon absorption of the cornea allows blue-IRIS to be performed with greater efficacy than when using 800-nm femtosecond laser pulses. Fresh cat corneas were obtained postmortem and cut into six wedges. Blue laser pulses at 400 nm, with 100-fs pulse duration at 80 MHz were used to micromachine phase gratings into each corneal wedge at scanning speeds from 1 to 15 mm/s. Grating lines were 1 μm wide, 5 μm apart, and 150 μm below the anterior corneal surface. Refractive index (RI) changes in micromachined regions were measured immediately by recording the diffraction efficiency of inscribed gratings. Six hours later, the corneas were processed for histology, and TUNEL staining was performed to assess whether blue-IRIS causes cell death. Scanning at 1 and 2 mm/s caused overt corneal damage in the form of bubbles and burns. At faster scanning speeds (5, 10, and 15 mm/s), phase gratings were created in the corneal stroma, which were shown to be pure RI changes ranging from 0.037 to 0.021 in magnitude. The magnitude of RI change was inversely related to scanning speed. TUNEL staining showed cell death only around bubbles and burns. Blue-IRIS can be performed safely and effectively in living cornea. Compared with near-infrared laser pulses, blue-IRIS enhances both achievable RI change and scanning speed without the need to dope the tissue with two-photon sensitizers, increasing the clinical applicability of this technique.
Xu, Lisen; Knox, Wayne H.; DeMagistris, Margaret; Wang, Nadan
2011-01-01
Purpose. To test the feasibility of intratissue refractive index shaping (IRIS) in living corneas by using 400-nm femtosecond (fs) laser pulses (blue-IRIS). To test the hypothesis that the intrinsic two-photon absorption of the cornea allows blue-IRIS to be performed with greater efficacy than when using 800-nm femtosecond laser pulses. Methods. Fresh cat corneas were obtained postmortem and cut into six wedges. Blue laser pulses at 400 nm, with 100-fs pulse duration at 80 MHz were used to micromachine phase gratings into each corneal wedge at scanning speeds from 1 to 15 mm/s. Grating lines were 1 μm wide, 5 μm apart, and 150 μm below the anterior corneal surface. Refractive index (RI) changes in micromachined regions were measured immediately by recording the diffraction efficiency of inscribed gratings. Six hours later, the corneas were processed for histology, and TUNEL staining was performed to assess whether blue-IRIS causes cell death. Results. Scanning at 1 and 2 mm/s caused overt corneal damage in the form of bubbles and burns. At faster scanning speeds (5, 10, and 15 mm/s), phase gratings were created in the corneal stroma, which were shown to be pure RI changes ranging from 0.037 to 0.021 in magnitude. The magnitude of RI change was inversely related to scanning speed. TUNEL staining showed cell death only around bubbles and burns. Conclusions. Blue-IRIS can be performed safely and effectively in living cornea. Compared with near-infrared laser pulses, blue-IRIS enhances both achievable RI change and scanning speed without the need to dope the tissue with two-photon sensitizers, increasing the clinical applicability of this technique. PMID:21931133
Yao, Qiu-Mei; Zhou, Jiao; Gale, Robert Peter; Li, Jin-Lan; Li, Ling-Di; Li, Ning; Chen, Shan-Shan; Ruan, Guo-Rui
2015-10-01
Calreticulin (CALR) mutations were recently identified in a substantial proportion of persons with essential thrombocythemia (ET) and with primary myelofibrosis (PMF) without JAK2(V617F). Consequently rapid, sensitive, and specific methods to detect and quantify these mutations are needed. We studied samples from 1088 persons with myeloproliferative neoplasms (MPNs) including 421 JAK2(V617F) negative subjects with ET, PMF, polycythemia vera (PV), chronic myeloid leukemia (CML) and hyper-eosinophilic syndrome (HES). Detection of CALR exon 9 mutations was done by PCR amplification followed by fragment length analysis and direct sequencing. Dilution assays were used to determine CALR mutant allele burden. We detected CALR mutations in blood and bone marrow samples from 152 subjects with ET and with PMF but not in samples from normal or persons with PV, CML, or HES. CALR mutant peaks were distinct from wild-type peaks and dilution experiments indicated a sensitivity level of 0.5-5% for a CALR mutant allele in a wild-type background. Diverse types of mutations were detected including deletions, insertions, and complex indels. All mutations were confirmed by direct sequencing. We also used dilution experiments to quantify mutant allele burden. We were able to reproducibly detect mutant allele levels as low 5% (0.5-5%) in a wild-type background. PCR amplification followed by fragment length analysis is a rapid, sensitive, and specific method for screening persons with MPNs for CALR mutations, especially those with ET and PMF and for estimating mutant allele burden.
Isolation and characterization of OmpC porin mutants with altered pore properties
DOE Office of Scientific and Technical Information (OSTI.GOV)
Misra, R.; Benson, S.A.
1988-02-01
The LamB protien is normally required for the uptake of maltodextrins. Starting with a LamB/sup -/ OmpF/sup -/ strain, we have isolated mutants that will grow on maltodextrins. The mutation conferring the Dex/sup +/ phenotype in the majority of these mutants has been mapped to the ompC locus. These mutants, unlike LamB/sup -/ OmpF/sup -/ strains, grew on maltotriose and maltotetraose, but not on maltopentaose, and showed a significantly higher rate of (/sup 14/C) maltose uptake than the parent strain did. In addition, these mutants showed increased sensitivity to certain ..beta..-lactam antibiotics and sodium dodecyl sulfate, but did not exhibitmore » an increase in sensitivity to other antibiotics and detergents. The nucleotide sequence of these mutants has been determined. In all cases, residue 74 (arginine) of the mature OmpC protein was affected. The results suggest that this region of the OmpC protein is involved in the pore domain and that the alterations lead to an increased pore size.« less
Zhu, Xiao Fang; Lei, Gui Jie; Wang, Zhi Wei; Shi, Yuan Zhi; Braam, Janet; Li, Gui Xin; Zheng, Shao Jian
2013-01-01
Whether aluminum toxicity is an apoplastic or symplastic phenomenon is still a matter of debate. Here, we found that three auxin overproducing mutants, yucca, the recessive mutant superroot2, and superroot1 had increased aluminum sensitivity, while a transfer DNA insertion mutant, xyloglucan endotransglucosylase/hydrolases15 (xth15), showed enhanced aluminum resistance, accompanied by low endogenous indole-3-acetic acid levels, implying that auxin may be involved in plant responses to aluminum stress. We used yucca and xth15 mutants for further study. The two mutants accumulated similar total aluminum in roots and had significantly reduced cell wall aluminum and increased symplastic aluminum content relative to the wild-type ecotype Columbia, indicating that altered aluminum levels in the symplast or cell wall cannot fully explain the differential aluminum resistance of these two mutants. The expression of Al sensitive1 (ALS1), a gene that functions in aluminum redistribution between the cytoplasm and vacuole and contributes to symplastic aluminum detoxification, was less abundant in yucca and more abundant in xth15 than the wild type, consistent with possible ALS1 function conferring altered aluminum sensitivity in the two mutants. Consistent with the idea that xth15 can tolerate more symplastic aluminum because of possible ALS1 targeting to the vacuole, morin staining of yucca root tip sections showed more aluminum accumulation in the cytosol than in the wild type, and xth15 showed reduced morin staining of cytosolic aluminum, even though yucca and xth15 had similar overall symplastic aluminum content. Exogenous application of an active auxin analog, naphthylacetic acid, to the wild type mimicked the aluminum sensitivity and distribution phenotypes of yucca, verifying that auxin may regulate aluminum distribution in cells. Together, these data demonstrate that auxin negatively regulates aluminum tolerance through altering ALS1 expression and aluminum distribution within plant cells, and plants must coordinate exclusion and internal detoxification to reduce aluminum toxicity effectively. PMID:23776189
Suzuki, Tetsuya; Grúz, Petr; Honma, Masamitsu; Adachi, Noritaka; Nohmi, Takehiko
2016-09-01
Translesion DNA polymerases (TLS pols) play critical roles in defense mechanisms against genotoxic agents. The defects or mutations of TLS pols are predicted to result in hypersensitivity of cells to environmental mutagens. In this study, human cells expressing DNA polymerase ζ (Pol ζ) variants with low fidelity or weak catalytic activity have been established with Nalm-6-MSH+ cells and their sensitivity to mutagenicity and cytotoxicity of benzo[a]pyrene diol epoxide (BPDE) and ultraviolet-C light (UV-C) was examined. The low-fidelity mutants were engineered by knocking-in DNA sequences that direct changes of leucine 2618 to either phenylalanine (L2618F) or methionine (L2618M) of Pol ζ. The weak-catalytic-activity mutants were generated by knocking-in DNA sequences that direct changes of either tyrosine 2779 to phenylalanine (Y2779F) or aspartate 2781 to asparagine (D2781N). In addition, a +1 frameshift mutation, i.e., CCC to CCCC, was introduced in the coding region of the TK1 gene to measure the mutant frequencies. Doubling time and spontaneous TK mutant frequencies of the established cell lines were similar to those of the wild-type cells. The low-fidelity mutants displayed, however, higher sensitivity to the mutagenicity of BPDE and UV-C than the wild-type cells although their cytotoxic sensitivity was not changed. In contrast, the weak-catalytic-activity mutants were more sensitive to the cytotoxicity of BPDE and UV-C than the wild-type cells, and displayed much higher sensitivity to the clastogenicity of BPDE than the wild-type cells in an in vitro micronucleus assay. These results indicate that human Pol ζ is involved in TLS across DNA lesions induced by BPDE and UV-C and also that the TLS plays important roles in induction of mutations, clastogenicity and in cellular survival of the damaged human cells. Similarities and differences in in vivo roles of yeast and human Pol ζ in genome integrity are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.
Targeting the Oxidative Stress Response System of Fungi with Redox-Potent Chemosensitizing Agents
Kim, Jong H.; Chan, Kathleen L.; Faria, Natália C. G.; Martins, M. de L.; Campbell, Bruce C.
2012-01-01
The cellular antioxidant system is a target in the antifungal action of amphotericin B (AMB) and itraconazole (ITZ), in filamentous fungi. The sakAΔ mutant of Aspergillus fumigatus, a mitogen-activated protein kinase (MAPK) gene deletion mutant in the antioxidant system, was found to be more sensitive to AMB or ITZ than other A. fumigatus strains, a wild type and a mpkCΔ mutant (a MAPK gene deletion mutant in the polyalcohol sugar utilization system). Complete fungal kill (≥99.9%) by ITZ or AMB was also achieved by much lower dosages for the sakAΔ mutant than for the other strains. It appears msnA, an Aspergillus ortholog to Saccharomyces cerevisiae MSN2 (encoding a stress-responsive C2H2-type zinc-finger regulator) and sakA and/or mpkC (upstream MAPKs) are in the same stress response network under tert-butyl hydroperoxide (t-BuOOH)-, hydrogen peroxide (H2O2)- or AMB-triggered toxicity. Of note is that ITZ-sensitive yeast pathogens were also sensitive to t-BuOOH, showing a connection between ITZ sensitivity and antioxidant capacity of fungi. Enhanced antifungal activity of AMB or ITZ was achieved when these drugs were co-applied with redox-potent natural compounds, 2,3-dihydroxybenzaldehyde, thymol or salicylaldehyde, as chemosensitizing agents. We concluded that redox-potent compounds, which target the antioxidant system in fungi, possess a chemosensitizing capacity to enhance efficacy of conventional drugs. PMID:22438852
Tran, Anh N.; Lai, Albert; Li, Sichen; Pope, Whitney B.; Teixeira, Stephanie; Harris, Robert J.; Woodworth, Davis C.; Nghiemphu, Phioanh L.; Cloughesy, Timothy F.; Ellingson, Benjamin M.
2014-01-01
Background Isocitrate dehydrogenase 1 (IDH1) mutations have been linked to favorable outcomes in patients with glioblastoma multiforme (GBM). Recent in vitro experiments suggest that IDH1 mutation sensitizes tumors to radiation damage. We hypothesized that radiographic treatment response would be significantly different between IDH1 mutant versus wild-type GBMs after radiotherapy (RT) and concurrent temozolomide (TMZ). Methods A total of 39 newly diagnosed GBM patients with known IDH1 mutational status (10 IDH1 mutants), who followed standard therapy and had regular post-contrast T1W (T1+C) and T2W/ fluid-attenuated inversion recovery (FLAIR) images in the 6-month period after starting RT, were enrolled. The volume of contrast-enhancing and FLAIR hyperintensity were calculated from each scan. Linear and polynomial regression techniques were used to estimate the rate of change and temporal patterns in tumor volumes. Results IDH1 mutant GBMs demonstrated a favorable response to RT/TMZ in the study period, as demonstrated by 10 of 10 mutants showing radiographic response (decreasing VT1+C), compared with 13 of 29 wild-types (P < .001). During the study period, VT1+C and VFLAIR changed at −3.6% per week and +0.6% per week in IDH1 mutant tumors, respectively, as compared with +0.8% per week and +5.2% per week in IDH1 wild-type tumors (P = .0076 and P = .0118, respectively). Amongst the radiographic responders, IDH1 mutant GBMs still demonstrated significant progression-free and overall survival benefit. Aggregated tumor kinetics by group showed significant lower rate in IDH1 mutant GBMs in specific periods: >105 days for VFLAIR and 95–120 and >150 days for VT1+C from starting RT/TMZ. Conclusions The current study supports the hypothesis that IDH1 mutant GBMs are more sensitive to radiochemotherapy than IDH1 wild-type GBMs. PMID:24305712
Microseed matrix screening for optimization in protein crystallization: what have we learned?
D'Arcy, Allan; Bergfors, Terese; Cowan-Jacob, Sandra W; Marsh, May
2014-09-01
Protein crystals obtained in initial screens typically require optimization before they are of X-ray diffraction quality. Seeding is one such optimization method. In classical seeding experiments, the seed crystals are put into new, albeit similar, conditions. The past decade has seen the emergence of an alternative seeding strategy: microseed matrix screening (MMS). In this strategy, the seed crystals are transferred into conditions unrelated to the seed source. Examples of MMS applications from in-house projects and the literature include the generation of multiple crystal forms and different space groups, better diffracting crystals and crystallization of previously uncrystallizable targets. MMS can be implemented robotically, making it a viable option for drug-discovery programs. In conclusion, MMS is a simple, time- and cost-efficient optimization method that is applicable to many recalcitrant crystallization problems.
Microseed matrix screening for optimization in protein crystallization: what have we learned?
D’Arcy, Allan; Bergfors, Terese; Cowan-Jacob, Sandra W.; Marsh, May
2014-01-01
Protein crystals obtained in initial screens typically require optimization before they are of X-ray diffraction quality. Seeding is one such optimization method. In classical seeding experiments, the seed crystals are put into new, albeit similar, conditions. The past decade has seen the emergence of an alternative seeding strategy: microseed matrix screening (MMS). In this strategy, the seed crystals are transferred into conditions unrelated to the seed source. Examples of MMS applications from in-house projects and the literature include the generation of multiple crystal forms and different space groups, better diffracting crystals and crystallization of previously uncrystallizable targets. MMS can be implemented robotically, making it a viable option for drug-discovery programs. In conclusion, MMS is a simple, time- and cost-efficient optimization method that is applicable to many recalcitrant crystallization problems. PMID:25195878
Magnetospheric Multiscale Instrument Suite Operations and Data System
NASA Technical Reports Server (NTRS)
Baker, D. N.; Riesberg, L.; Pankratz, C. K.; Panneton, R. S.; Giles, B. L.; Wilder, F. D.; Ergun, R. E.
2015-01-01
The four Magnetospheric Multiscale (MMS) spacecraft will collect a combined volume of approximately 100 gigabits per day of particle and field data. On average, only 4 gigabits of that volume can be transmitted to the ground. To maximize the scientific value of each transmitted data segment, MMS has developed the Science Operations Center (SOC) to manage science operations, instrument operations, and selection, downlink, distribution, and archiving of MMS science data sets. The SOC is managed by the Laboratory for Atmospheric and Space Physics (LASP) in Boulder, Colorado and serves as the primary point of contact for community participation in the mission. MMS instrument teams conduct their operations through the SOC, and utilize the SOC's Science Data Center (SOC) for data management and distribution. The SOC provides a single mission data archive for the housekeeping and science data, calibration data, ephemerides, attitude and other ancillary data needed to support the scientific use and interpretation. All levels of data products will reside at and be publicly disseminated from the SDC. Documentation and metadata describing data products, algorithms, instrument calibrations, validation, and data quality will be provided. Arguably, the most important innovation developed by the SOC is the MMS burst data management and selection system. With nested automation and 'Scientist-in-the-Loop' (SITL) processes, these systems are designed to maximize the value of the burst data by prioritizing the data segments selected for transmission to the ground. This paper describes the MMS science operations approach, processes and data systems, including the burst system and the SITL concept.
Magnetospheric Multiscale Instrument Suite Operations and Data System
NASA Astrophysics Data System (ADS)
Baker, D. N.; Riesberg, L.; Pankratz, C. K.; Panneton, R. S.; Giles, B. L.; Wilder, F. D.; Ergun, R. E.
2016-03-01
The four Magnetospheric Multiscale (MMS) spacecraft will collect a combined volume of ˜100 gigabits per day of particle and field data. On average, only 4 gigabits of that volume can be transmitted to the ground. To maximize the scientific value of each transmitted data segment, MMS has developed the Science Operations Center (SOC) to manage science operations, instrument operations, and selection, downlink, distribution, and archiving of MMS science data sets. The SOC is managed by the Laboratory for Atmospheric and Space Physics (LASP) in Boulder, Colorado and serves as the primary point of contact for community participation in the mission. MMS instrument teams conduct their operations through the SOC, and utilize the SOC's Science Data Center (SDC) for data management and distribution. The SOC provides a single mission data archive for the housekeeping and science data, calibration data, ephemerides, attitude and other ancillary data needed to support the scientific use and interpretation. All levels of data products will reside at and be publicly disseminated from the SDC. Documentation and metadata describing data products, algorithms, instrument calibrations, validation, and data quality will be provided. Arguably, the most important innovation developed by the SOC is the MMS burst data management and selection system. With nested automation and "Scientist-in-the-Loop" (SITL) processes, these systems are designed to maximize the value of the burst data by prioritizing the data segments selected for transmission to the ground. This paper describes the MMS science operations approach, processes and data systems, including the burst system and the SITL concept.
Scala, Marcello; Fiaschi, Pietro; Capra, Valeria; Garrè, Maria Luisa; Tortora, Domenico; Ravegnani, Marcello; Pavanello, Marco
2018-07-01
Moyamoya disease (MMD) is a cerebrovascular disorder characterized by the progressive occlusion of the supraclinoid internal carotid artery (ICA), resulting in the formation of an abnormal cerebral vascular network. When MMD occurs in association with an underlying medical condition, including some distinctive genetic disorders, it is named moyamoya syndrome (MMS). The discrimination between MMD and MMS has been validated by recent genetic researches and international reviews. Similarly to patients suffering from MMD, patients with MMS generally become symptomatic because of ischemic complications, which lead to hemiparesis, transient ischemic events, seizures, and sensory symptoms. RASopathies are a group of neurodevelopmental disorders that can be associated with MMS. We retrospectively reviewed 18 RASopathy patients with MMS treated at our institution from 2000 to 2015 (16 neurofibromatosis type 1, 1 Costello syndrome, and 1 Schimmelpenning syndrome). Here, we report clinical data, performed surgical procedures, and clinic-radiological outcome of these patients. Most of them received both indirect revascularization and medical therapy. At the moment, there are no univocal recommendations on which of these two treatment strategies is the treatment of choice in patients with RASopathies and MMS. We suggest that patients with a good overall prognosis (primarily depending on the distinctive underlying genetic disorder) and initial cerebrovascular disease could benefit from a prophylactic surgical revascularization, in order to prevent the cognitive impairment due to the progression of the vasculopathy.
Pyne, Prosenjit; Alam, Masrure; Rameez, Moidu Jameela; Mandal, Subhrangshu; Sar, Abhijit; Mondal, Nibendu; Debnath, Utsab; Mathew, Boby; Misra, Anup Kumar; Mandal, Amit Kumar; Ghosh, Wriddhiman
2018-04-18
The SoxXAYZB(CD) 2 -mediated pathway of bacterial sulfur-chemolithotrophy explains the oxidation of thiosulfate, sulfide, sulfur and sulfite, but not tetrathionate. Advenella kashmirensis, which oxidizes tetrathionate to sulfate, besides forming it as an intermediate during thiosulfate-oxidation, possesses a soxCDYZAXOB operon. Knock-out-mutations proved that only SoxBCD is involved in A. kashmirensis tetrathionate-oxidation, whereas thiosulfate-to-tetrathionate-conversion is Sox-independent. Expression of two glutathione-metabolism-related proteins increased under chemolithotrophic conditions, as compared to the chemoorganotrophic one. Substrate-dependent oxygen-consumption pattern of whole-cells, and sulfur-oxidizing enzyme activities of cell-free-extracts, measured in the presence/absence of thiol-inhibitors/glutathione, corroborated glutathione-involvement in tetrathionate-oxidation. Furthermore, proteome analyses detected a sulfite:acceptor oxidoreductase (SorAB) exclusively under chemolithotrophic conditions, while expression of a methanol dehydrogenase (XoxF) homolog, subsequently named thiol dehydrotransferase (ThdT), was found to increase three- and ten-fold during thiosulfate-to-tetrathionate-conversion and tetrathionate-oxidation, respectively. A thdT-knocked-out mutant did not oxidize tetrathionate, but converted half of the supplied 40-mM-S thiosulfate to tetrathionate. Knock-out of another thiosulfate dehydrogenase (tsdA) gene proved that both ThdT and TsdA individually converted ∼20-mM-S thiosulfate to tetrathionate. The overexpressed and isolated ThdT protein exhibited PQQ-dependent thiosulfate dehydrogenation, whereas its PQQ-independent thiol-transfer activity involving tetrathionate and glutathione potentially produced a glutathione:sulfodisulfane adduct and sulfite. SoxBCD and SorAB were hypothesized to oxidize the aforesaid adduct and sulfite, respectively. This article is protected by copyright. All rights reserved. © 2018 John Wiley & Sons Ltd.
Ramón-Carbonell, Marta de; Sánchez-Torres, Paloma
2017-10-01
A putative sucrose transporter PdSUT1 included in the same clade that Sut1p from Schizosaccharomyces pombe was identified in Penicillium digitatum, the major citrus postharvest pathogen. PdSUT1 gene was characterized using target gene disruption and gene overexpression. The ΔPdSUT1 mutants generated by gene elimination showed reduction in fungal virulence during citrus fruit infection assayed in mature fruit at 20°C. However, the overexpression mutants did not increased disease severity neither in the mutants coming from a high virulent nor from a low virulent P. digitatum progenitor strains. Moreover, fungicide sensitivity was affected in the deletant mutants but not in the overexpression transformants. The expression analysis of several genes involved in fungicide resistance showed an intensification of MFS transporters and a decrease of sterol demethylases transcriptional abundance in the ΔPdSUT1 mutants compare to the parental wild type strain. PdSUT1 appear not to be directly involved in fungicide resistance although can affect the gene expression of fungicide related genes. These results indicate that PdSUT1 contribute to P. digitatum fungal virulence and influence fungicide sensitivity through carbohydrate uptake and MFS transporters gene activation. Copyright © 2017 Elsevier GmbH. All rights reserved.
JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors
Gao, Sizhi P.; Chang, Qing; Mao, Ninghui; Daly, Laura A.; Vogel, Robert; Chan, Tyler; Liu, Shu Hui; Bournazou, Eirini; Schori, Erez; Zhang, Haiying; Brewer, Monica Red; Pao, William; Morris, Luc; Ladanyi, Marc; Arcila, Maria; Manova-Todorova, Katia; de Stanchina, Elisa; Norton, Larry; Levine, Ross L.; Altan-Bonnet, Gregoire; Solit, David; Zinda, Michael; Huszar, Dennis; Lyden, David; Bromberg, Jacqueline F.
2016-01-01
Lung adenocarcinomas with mutant epidermal growth factor receptor (EGFR) respond to EGFR-targeted tyrosine kinase inhibitors (TKIs), but resistance invariably occurs. We found that the Janus kinase (JAK)/signal transduction and activator of transcription 3 (STAT3) signaling pathway was aberrantly increased in TKI-resistant EGFR-mutant non–small cell lung cancer (NSCLC) cells. JAK2 inhibition restored sensitivity to the EGFR inhibitor erlotinib in TKI-resistant cell lines and xenograft models of EGFR-mutant TKI-resistant lung cancer. JAK2 inhibition uncoupled EGFR from its negative regulator, suppressor of cytokine signaling 5 (SOCS5), consequently increasing EGFR abundance and restoring the tumor cells’ dependence on EGFR signaling. Furthermore, JAK2 inhibition led to heterodimerization of mutant and wild-type EGFR subunits, the activity of which was then blocked by TKIs. Our results reveal a mechanism whereby JAK2 inhibition overcomes acquired resistance to EGFR inhibitors and support the use of combination therapy with JAK and EGFR inhibitors for the treatment of EGFR-dependent NSCLC. PMID:27025877
Patterson, B; Ruppel, K M; Wu, Y; Spudich, J A
1997-10-31
Cold-sensitive myosin mutants represent powerful tools for dissecting discrete deficiencies in myosin function. Biochemical characterization of two such mutants, G680V and G691C, has allowed us to identify separate facets of myosin motor function perturbed by each alteration. Compared with wild type, the G680V myosin exhibits a substantially enhanced affinity for several nucleotides, decreased ATPase activity, and overoccupancy or creation of a novel strongly actin-binding state. The properties of the novel strong binding state are consistent with a partial arrest or pausing at the onset of the mechanical stroke. The G691C mutant, on the other hand, exhibits an elevated basal ATPase indicative of premature phosphate release. By releasing phosphate without a requirement for actin binding, the G691C can bypass the part of the cycle involving the mechanical stroke. The two mutants, despite having alterations in glycine residues separated by only 11 residues, have dramatically different consequences on the mechanochemical cycle.
NASA Technical Reports Server (NTRS)
Solimani, Jason A.; Rosanova, Santino
2015-01-01
Thermocouples require two thin wires to be routed out of the spacecraft to connect to the ground support equipment used to monitor and record the temperature data. This large number of wires that exit the observatory complicates integration and creates an undesirable heat path during testing. These wires exiting the spacecraft need to be characterized as a thermal short that will not exist during flight. To minimize complexity and reduce thermal variables from these ground support equipment (GSE) wires, MMS pursued a hybrid path for temperature monitoring, utilizing thermocouples and digital 1-wire temperature sensors. Digital 1-wire sensors can greatly reduce harness mass, length and complexity as they can be spliced together. For MMS, 350 digital 1-wire sensors were installed on the spacecraft with only 18 wires exiting as opposed to a potential 700 thermocouple wires. Digital 1-wire sensors had not been used in such a large scale at NASAGSFC prior to the MMS mission. During the MMS thermal vacuum testing a lessons learned matrix was formulated that will assist future integration of 1-wires into thermal testing and one day into flight.
Perceptual video quality comparison of 3DTV broadcasting using multimode service systems
NASA Astrophysics Data System (ADS)
Ok, Jiheon; Lee, Chulhee
2015-05-01
Multimode service (MMS) systems allow broadcasters to provide multichannel services using a single HD channel. Using these systems, it is possible to provide 3DTV programs that can be watched either in three-dimensional (3-D) or two-dimensional (2-D) modes with backward compatibility. In the MMS system for 3DTV broadcasting using the Advanced Television Systems Committee standards, the left and the right views are encoded using MPEG-2 and H.264, respectively, and then transmitted using a dual HD streaming format. The left view, encoded using MPEG-2, assures 2-D backward compatibility while the right view, encoded using H.264, can be optionally combined with the left view to generate stereoscopic 3-D views. We analyze 2-D and 3-D perceptual quality when using the MMS system by comparing items in the frame-compatible format (top-bottom), which is a conventional transmission scheme for 3-D broadcasting. We performed perceptual 2-D and 3-D video quality evaluation assuming 3DTV programs are encoded using the MMS system and top-bottom format. The results show that MMS systems can be preferable with regard to perceptual 2-D and 3-D quality and backward compatibility.
In-Flight Calibration Processes for the MMS Fluxgate Magnetometers
NASA Astrophysics Data System (ADS)
Bromund, K. R.; Leinweber, H. K.; Plaschke, F.; Strangeway, R. J.; Magnes, W.; Fischer, D.; Nakamura, R.; Anderson, B. J.; Russell, C. T.; Baumjohann, W.; Chutter, M.; Torbert, R. B.; Le, G.; Slavin, J. A.; Kepko, L.
2015-12-01
The calibration effort for the Magnetospheric Multiscale Mission (MMS) Analog Fluxgate (AFG) and Digital Fluxgate (DFG) magnetometers is a coordinated effort between three primary institutions: University of California, Los Angeles (UCLA); Space Research Institute, Graz, Austria (IWF); and Goddard Space Flight Center (GSFC). Since the successful deployment of all 8 magnetometers on 17 March 2015, the effort to confirm and update the ground calibrations has been underway during the MMS commissioning phase. The in-flight calibration processes evaluate twelve parameters that determine the alignment, orthogonalization, offsets, and gains for all 8 magnetometers using algorithms originally developed by UCLA and the Technical University of Braunschweig and tailored to MMS by IWF, UCLA, and GSFC. We focus on the processes run at GSFC to determine the eight parameters associated with spin tones and harmonics. We will also discuss the processing flow and interchange of parameters between GSFC, IWF, and UCLA. IWF determines the low range spin axis offsets using the Electron Drift Instrument (EDI). UCLA determines the absolute gains and sensor azimuth orientation using Earth field comparisons. We evaluate the performance achieved for MMS and give examples of the quality of the resulting calibrations.
Global Positioning System Navigation Above 76,000 km for NASA's Magnetospheric Multiscale Mission
NASA Technical Reports Server (NTRS)
Winternitz, Luke B.; Bamford, William A.; Price, Samuel R.; Carpenter, J. Russell; Long, Anne C.; Farahmand, Mitra
2016-01-01
NASA's Magnetospheric Multiscale (MMS) mission, launched in March of 2015, consists of a controlled formation of four spin-stabilized spacecraft in similar highly elliptic orbits reaching apogee at radial distances of 12 and 25 Earth radii (RE) in the first and second phases of the mission. Navigation for MMS is achieved independently on-board each spacecraft by processing Global Positioning System (GPS) observables using NASA Goddard Space Flight Center (GSFC)'s Navigator GPS receiver and the Goddard Enhanced Onboard Navigation System (GEONS) extended Kalman filter software. To our knowledge, MMS constitutes, by far, the highest-altitude operational use of GPS to date and represents a high point of over a decade of high-altitude GPS navigation research and development at GSFC. In this paper we will briefly describe past and ongoing high-altitude GPS research efforts at NASA GSFC and elsewhere, provide details on the design of the MMS GPS navigation system, and present on-orbit performance data from the first phase. We extrapolate these results to predict performance in the second phase orbit, and conclude with a discussion of the implications of the MMS results for future high-altitude GPS navigation, which we believe to be broad and far-reaching.
Cowan, Natasha; Goldenberg, Alina; Basu, Pallavi; Eilers, Robert; Hau, Jennifer; I Brian Jiang, Shang
2018-05-01
Clinically large cutaneous tumors and those with aggressive subclinical extension (ASE) often require wider margins and increased operative time during Mohs micrographic surgery (MMS). Our goal is to improve dermatologic surgeons' counseling information on complication risks for aggressive tumors. To examine the incidence of postoperative complications in MMS patients, with a focus on differences between aggressive and non-aggressive tumors. We performed a retrospective cross-sectional chart review of 4151 MMS cases at the University of California, San Diego. A postoperative complication was defined as an adverse event directly related to MMS reported within 6 weeks of the procedure. Clinically, large tumors had 50 times the odds of postoperative complication as compared to all other tumors (P less than 0.001). ASE was not found to be significantly associated with higher rates of postoperative complications when controlled for other factors. Clinically, large tumors may be at higher risk for complications following MMS due to their increased size and need for repair with methods other than linear closures. Tumors with ASE were not found to be at higher risk for postoperative complications. J Drugs Dermatol. 2018;17(5):511-515.
Magnetospheric MultiScale (MMS) System Manager
NASA Technical Reports Server (NTRS)
Schiff, Conrad; Maher, Francis Alfred; Henely, Sean Philip; Rand, David
2014-01-01
The Magnetospheric MultiScale (MMS) mission is an ambitious NASA space science mission in which 4 spacecraft are flown in tight formation about a highly elliptical orbit. Each spacecraft has multiple instruments that measure particle and field compositions in the Earths magnetosphere. By controlling the members relative motion, MMS can distinguish temporal and spatial fluctuations in a way that a single spacecraft cannot.To achieve this control, 2 sets of four maneuvers, distributed evenly across the spacecraft must be performed approximately every 14 days. Performing a single maneuver on an individual spacecraft is usually labor intensive and the complexity becomes clearly increases with four. As a result, the MMS flight dynamics team turned to the System Manager to put the routine or error-prone under machine control freeing the analysts for activities that require human judgment.The System Manager is an expert system that is capable of handling operations activities associated with performing MMS maneuvers. As an expert system, it can work off a known schedule, launching jobs based on a one-time occurrence or on a set reoccurring schedule. It is also able to detect situational changes and use event-driven programming to change schedules, adapt activities, or call for help.
Data Processing and Quality Evaluation of a Boat-Based Mobile Laser Scanning System
Vaaja, Matti; Kukko, Antero; Kaartinen, Harri; Kurkela, Matti; Kasvi, Elina; Flener, Claude; Hyyppä, Hannu; Hyyppä, Juha; Järvelä, Juha; Alho, Petteri
2013-01-01
Mobile mapping systems (MMSs) are used for mapping topographic and urban features which are difficult and time consuming to measure with other instruments. The benefits of MMSs include efficient data collection and versatile usability. This paper investigates the data processing steps and quality of a boat-based mobile mapping system (BoMMS) data for generating terrain and vegetation points in a river environment. Our aim in data processing was to filter noise points, detect shorelines as well as points below water surface and conduct ground point classification. Previous studies of BoMMS have investigated elevation accuracies and usability in detection of fluvial erosion and deposition areas. The new findings concerning BoMMS data are that the improved data processing approach allows for identification of multipath reflections and shoreline delineation. We demonstrate the possibility to measure bathymetry data in shallow (0–1 m) and clear water. Furthermore, we evaluate for the first time the accuracy of the BoMMS ground points classification compared to manually classified data. We also demonstrate the spatial variations of the ground point density and assess elevation and vertical accuracies of the BoMMS data. PMID:24048340
Data processing and quality evaluation of a boat-based mobile laser scanning system.
Vaaja, Matti; Kukko, Antero; Kaartinen, Harri; Kurkela, Matti; Kasvi, Elina; Flener, Claude; Hyyppä, Hannu; Hyyppä, Juha; Järvelä, Juha; Alho, Petteri
2013-09-17
Mobile mapping systems (MMSs) are used for mapping topographic and urban features which are difficult and time consuming to measure with other instruments. The benefits of MMSs include efficient data collection and versatile usability. This paper investigates the data processing steps and quality of a boat-based mobile mapping system (BoMMS) data for generating terrain and vegetation points in a river environment. Our aim in data processing was to filter noise points, detect shorelines as well as points below water surface and conduct ground point classification. Previous studies of BoMMS have investigated elevation accuracies and usability in detection of fluvial erosion and deposition areas. The new findings concerning BoMMS data are that the improved data processing approach allows for identification of multipath reflections and shoreline delineation. We demonstrate the possibility to measure bathymetry data in shallow (0-1 m) and clear water. Furthermore, we evaluate for the first time the accuracy of the BoMMS ground points classification compared to manually classified data. We also demonstrate the spatial variations of the ground point density and assess elevation and vertical accuracies of the BoMMS data.
Koslosky, Cynthia Lynn; El Tal, Abdel Kader; Workman, Benjamin; Tamim, Hani; Durance, Michelle Christine; Mehregan, David Ali
2014-09-01
Skin biopsy reports of basal cell carcinoma and squamous cell carcinoma are often accompanied by comments on the margins. A physician's management can be influenced by such reports, particularly when the margins are reported as clear and no further interventions are pursued. To retrospectively review pathology margins on Mohs micrographic surgery (MMS) cases performed at a University Center and to compare biopsy margins with the Mohs margins found on the first stage. Data collection of 1,000 cases of Mohs surgery was obtained regarding margins on skin biopsy and compared with margins on the first stage of MMS. Overall, of the biopsies that showed only deep margin involvement, a lateral margin was seen on 32% of the first stages of MMS. Conversely, of the biopsies that showed only lateral margin involvement, a deep margin was seen on 14% of the first stages of MMS. Of the biopsies that showed clear margins, a margin was seen in 30% of the cases on the first stage of MMS. Skin biopsies processed through the "bread-loafing" technique are not reliable in detecting accurate margins, and therefore, a biopsy report should not include margin involvement within it.
Wang, Pu; Wu, Jing; Ma, Shenghong; Zhang, Lei; Yao, Jun; Hoadley, Katherine A; Wilkerson, Matthew D; Perou, Charles M; Guan, Kun-Liang; Ye, Dan; Xiong, Yue
2015-12-22
Chemotherapy of a combination of DNA alkylating agents, procarbazine and lomustine (CCNU), and a microtubule poison, vincristine, offers a significant benefit to a subset of glioma patients. The benefit of this regimen, known as PCV, was recently linked to IDH mutation that occurs frequently in glioma and produces D-2-hydroxyglutarate (D-2-HG), a competitive inhibitor of α-ketoglutarate (α-KG). We report here that D-2-HG inhibits the α-KG-dependent alkB homolog (ALKBH) DNA repair enzymes. Cells expressing mutant IDH display reduced repair kinetics, accumulate more DNA damages, and are sensitized to alkylating agents. The observed sensitization to alkylating agents requires the catalytic activity of mutant IDH to produce D-2-HG and can be reversed by the deletion of mutant IDH allele or overexpression of ALKBH2 or AKLBH3. Our results suggest that impairment of DNA repair may contribute to tumorigenesis driven by IDH mutations and that alkylating agents may merit exploration for treating IDH-mutated cancer patients. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
30 CFR 227.301 - What are a State's responsibilities if it performs audits?
Code of Federal Regulations, 2010 CFR
2010-07-01
... Audit Strategy, which MMS will develop in consultation with States having delegated audit authority; (c) Agree to undertake special audit initiatives MMS identifies targeting specific royalty issues, such as...
Shin, Hyoseung; Kim, Dong Hyun; Ryu, Hyeong Ho; Yoon, So Young; Jo, Seong Jin
2014-03-01
We evaluated the diagnostic accuracy of teleconsultations for skin diseases common in the army using a smartphone multimedia messaging service (MMS). Images of skin lesions were obtained from 100 army patients using digital cameras built into smartphones. Three remotely located dermatologists received the dermatology images and associated clinical information via the MMS. The teledermatologists' diagnoses were compared with those obtained from face-to-face examinations. The three most common diagnoses made at the dermatology clinics were eczema, viral warts and fungal infections. The mean diagnostic agreement between face-to-face and teledermatology consultations was 71% (SD 2). The mean kappa coefficient was 0.73 (SD 0.06) for the three most common diagnostic categories. The mean values for sensitivity were 78% (SD 0), 88% (SD 21) and 61% (SD 11) for eczema, viral warts and fungal infections, respectively, and the specificity values were above 90% for these skin diseases. Teledermatology consultation using smartphones is simple. Although diagnoses using telemedicine do not perfectly match diagnoses from face-to-face consultations the diagnostic accuracy using smartphones is superior to that of clinicians who are not specialized in dermatology.
Rössl, Anthony; Bentley-DeSousa, Amanda; Tseng, Yi-Chieh; Nwosu, Christine; Downey, Michael
2016-10-01
Nicotinamide is both a reaction product and an inhibitor of the conserved sirtuin family of deacetylases, which have been implicated in a broad range of cellular functions in eukaryotes from yeast to humans. Phenotypes observed following treatment with nicotinamide are most often assumed to stem from inhibition of one or more of these enzymes. Here, we used this small molecule to inhibit multiple sirtuins at once during treatment with DNA damaging agents in the Saccharomyces cerevisiae model system. Since sirtuins have been previously implicated in the DNA damage response, we were surprised to observe that nicotinamide actually increased the survival of yeast cells exposed to the DNA damage agent MMS. Remarkably, we found that enhanced resistance to MMS in the presence of nicotinamide was independent of all five yeast sirtuins. Enhanced resistance was also independent of the nicotinamide salvage pathway, which uses nicotinamide as a substrate to generate NAD+, and of a DNA damage-induced increase in the salvage enzyme Pnc1 Our data suggest a novel and unexpected function for nicotinamide that has broad implications for its use in the study of sirtuin biology across model systems. Copyright © 2016 by the Genetics Society of America.
Rössl, Anthony; Bentley-DeSousa, Amanda; Tseng, Yi-Chieh; Nwosu, Christine; Downey, Michael
2016-01-01
Nicotinamide is both a reaction product and an inhibitor of the conserved sirtuin family of deacetylases, which have been implicated in a broad range of cellular functions in eukaryotes from yeast to humans. Phenotypes observed following treatment with nicotinamide are most often assumed to stem from inhibition of one or more of these enzymes. Here, we used this small molecule to inhibit multiple sirtuins at once during treatment with DNA damaging agents in the Saccharomyces cerevisiae model system. Since sirtuins have been previously implicated in the DNA damage response, we were surprised to observe that nicotinamide actually increased the survival of yeast cells exposed to the DNA damage agent MMS. Remarkably, we found that enhanced resistance to MMS in the presence of nicotinamide was independent of all five yeast sirtuins. Enhanced resistance was also independent of the nicotinamide salvage pathway, which uses nicotinamide as a substrate to generate NAD+, and of a DNA damage-induced increase in the salvage enzyme Pnc1. Our data suggest a novel and unexpected function for nicotinamide that has broad implications for its use in the study of sirtuin biology across model systems. PMID:27527516
Maintaining Genome Stability: The Role of Helicases and Deaminases
2006-07-01
functional for replication. Then, we screened the surviving transformants for sensitivity to hydroxyurea . Our first screen was conducted under conditions...that are lethal for checkpoint mutants such as ∆rad3. We did not observe any hydroxyurea -sensitive MCM clones. However, following the old genetics...this kinase. In particular, we observe that an mcm4ts mutant blocked in hydroxyurea , and then released to restrictive temperature, is competent to
Maintaining Genome Stability: The Role of Helicases and Deaminases
2007-07-01
transformants for sensitivity to hydroxyurea . Our first screen was conducted under conditions that are lethal for checkpoint mutants such as ∆rad3...We did not observe any hydroxyurea -sensitive MCM clones. However, following the old genetics adage “absence of evidence is not evidence of... hydroxyurea , and then released to restrictive temperature, is competent to complete replication and go on to divide. In contrast, this mutant shifted
MMS Encounters with Reconnection Diffusion Regions in the Earth's Magnetotail
NASA Astrophysics Data System (ADS)
Torbert, R. B.; Burch, J. L.; Argall, M. R.; Farrugia, C. J.; Alm, L.; Dors, I.; Payne, D.; Rogers, A. J.; Strangeway, R. J.; Phan, T.; Ergun, R.; Goodrich, K.; Lindqvist, P. A.; Khotyaintsev, Y. V.; Giles, B. L.; Rager, A. C.; Gershman, D. J.; Kletzing, C.
2017-12-01
The Magnetospheric Multiscale (MMS) fleet of four spacecraft traversed the Earth's magnetotail in May through August of 2017 with an apogee of 25 Re, and encountered diffusion regions characteristic of symmetric reconnection. This presentation will describe in-situ measurements of large electric fields, strong electron cross-tail and Hall currents, and electron velocity distributions (frequently crescent-shaped) that are commonly observed in these regions. Positive electromagnetic energy conversion is also typical. The characteristics of symmetric reconnection observations will be contrasted with those of asymmetric reconnection that MMS observed previously at the dayside magnetopause.
Bilateral medial medullary syndrome secondary to Takayasu arteritis.
Deshpande, Anirudda; Chandran, Vijay; Pai, Aparna; Rao, Suryanarayana; Shetty, Ranjan
2013-08-13
Medial medullary syndrome (MMS) is a rare type of stroke which results due to occlusion of the anterior spinal artery or vertebral artery or its branches. In this case report we present a patient who developed MMS secondary to Takayasu arteritis (TA). TA is a chronic inflammatory arteritis primarily involving the arch of aorta and its branches, which in our patient resulted in occlusion of subclavian arteries as well as infarction of the medial medulla bilaterally. To our knowledge this is the first time that MMS has been found to occur secondary to TA.
2015-01-12
The protective covers are removed from around the solar panels on the upper stack of the Magnetospheric Multiscale spacecraft, or MMS, in the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. Preparations are underway for illumination testing of the spacecraft's upper stack. Illumination testing of the lower instrumentation payload stack was completed in December. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Kim Shiflett
2015-01-12
The protective covers are removed from around the solar panels on the upper stack of the Magnetospheric Multiscale spacecraft, or MMS, in the Astrotech payload processing facility in Titusville, Florida, near Kennedy Space Center. Preparations are underway for illumination testing of the spacecraft's upper stack. Illumination testing of the lower instrumentation payload stack was completed in December. Launch aboard a United Launch Alliance Atlas V rocket from Space Launch Complex 41 on Cape Canaveral Air Force Station is targeted for March 12. To learn more about MMS, visit http://www.nasa.gov/mms. Photo credit: NASA/Kim Shiflett
Jenks, Peter J.; Ferrero, Richard L.; Tankovic, Jacques; Thiberge, Jean-Michel; Labigne, Agnès
2000-01-01
The main objectives of this study were to determine whether the nitroreductase enzyme encoded by the rdxA gene of Helicobacter pylori was responsible for reductive activation of nitrofurantoin and whether a triple-therapy regimen with nitrofurantoin was able to eradicate metronidazole-sensitive and -resistant H. pylori infections from mice. The susceptibilities to nitrofurantoin of parent and isogenic rdxA mutant strains (three pairs), as well as a series of matched metronidazole-sensitive and -resistant strains isolated from mice (30) and patients (20), were assessed by agar dilution determination of the MIC. Groups of mice colonized with the metronidazole-sensitive H. pylori SS1 strain or a metronidazole-resistant rdxA SS1 mutant were treated with either metronidazole or nitrofurantoin as part of a triple-therapy regimen. One month after the completion of treatment the mice were sacrificed and their stomachs were cultured for H. pylori. The nitrofurantoin MICs for all strains tested were between 0.5 and 4.0 μg/ml. There was no significant difference between the susceptibility to nitrofurantoin of the parental strains and those of respective rdxA mutants or between those of matched metronidazole-sensitive and -resistant H. pylori isolates. The regimen with metronidazole eradicated infection from all eight SS1-infected mice and from one of eight mice inoculated with the rdxA mutant (P ≤ 0.001). The regimen with nitrofurantoin failed to eradicate infection from any of the six SS1-infected mice (P ≤ 0.001) and cleared infection from one of seven mice inoculated with the rdxA mutant. These results demonstrate that, despite the good in vitro activity of nitrofurantoin against H. pylori and the lack of cross-resistance between metronidazole and nitrofurantoin, eradication regimens involving nitrofurantoin are unable to eradicate either metronidazole-sensitive or -resistant H. pylori infections from mice. PMID:10991835
The Reliability and Validity of the Computerized Double Inclinometer in Measuring Lumbar Mobility
MacDermid, Joy Christine; Arumugam, Vanitha; Vincent, Joshua Israel; Carroll, Krista L
2014-01-01
Study Design : Repeated measures reliability/validity study. Objectives : To determine the concurrent validity, test-retest, inter-rater and intra-rater reliability of lumbar flexion and extension measurements using the Tracker M.E. computerized dual inclinometer (CDI) in comparison to the modified-modified Schober (MMS) Summary of Background : Numerous studies have evaluated the reliability and validity of the various methods of measuring spinal motion, but the results are inconsistent. Differences in equipment and techniques make it difficult to correlate results. Methods : Twenty subjects with back pain and twenty without back pain were selected through convenience sampling. Two examiners measured sagittal plane lumbar range of motion for each subject. Two separate tests with the CDI and one test with the MMS were conducted. Each test consisted of three trials. Instrument and examiner order was randomly assigned. Intra-class correlations (ICCs 2, 2 and 2, 2) and Pearson correlation coefficients (r) were used to calculate reliability and concurrent validity respectively. Results : Intra-trial reliability was high to very high for both the CDI (ICCs 0.85 - 0.96) and MMS (ICCs 0.84 - 0.98). However, the reliability was poor to moderate, when the CDI unit had to be repositioned either by the same rate (ICCs 0.16 - 0.59) or a different rater (ICCs 0.45 - 0.52). Inter-rater reliability for the MMS was moderate to high (ICCs 0.75 - 0.82) which bettered the moderate correlation obtained for the CDI (ICCs 0.45 - 0.52). Correlations between the CDI and MMS were poor for flexion (0.32; p<0.05) and poor to moderate (-0.42 - -0.51; p<0.05) for extension measurements. Conclusion : When using the CDI, an average of subsequent tests is required to obtain moderate reliability. The MMS was highly reliable than the CDI. The MMS and the CDI measure lumbar movement on a different metric that are not highly related to each other. PMID:25352928
NASA Technical Reports Server (NTRS)
Wood, Paul; Gramling, Cheryl; Stone, John; Smith, Patrick; Reiter, Jenifer
2016-01-01
This paper discusses commissioning of NASAs Magnetospheric MultiScale (MMS) Mission. The mission includes four identical spacecraft with a large, complex set of instrumentation. The planning for and execution of commissioning for this mission is described. The paper concludes by discussing lessons learned.
30 CFR 285.224 - What happens if MMS accepts my bid?
Code of Federal Regulations, 2010 CFR
2010-07-01
... RENEWABLE ENERGY ALTERNATE USES OF EXISTING FACILITIES ON THE OUTER CONTINENTAL SHELF Issuance of OCS Renewable Energy Leases Competitive Lease Award Process § 285.224 What happens if MMS accepts my bid? If we...
30 CFR 285.822 - What must I do when MMS conducts an inspection?
Code of Federal Regulations, 2010 CFR
2010-07-01
... OFFSHORE RENEWABLE ENERGY ALTERNATE USES OF EXISTING FACILITIES ON THE OUTER CONTINENTAL SHELF... (including your project easement) or grant; and (2) Make the following available for MMS to inspect: (i) The...
30 CFR 250.1507 - How will MMS measure training results?
Code of Federal Regulations, 2010 CFR
2010-07-01
... program, using one or more of the methods in this section. (a) Training system audit. MMS or its authorized representative may conduct a training system audit at your office. The training system audit will...
Moiseeva, Tatiana; Gamper, Armin M.; Hood, Brian; Conrads, Thomas P.; Bakkenist, Christopher J.
2016-01-01
We describe a dynamic phosphorylation on serine-1940 of the catalytic subunit of human Pol ε, POLE1, following DNA damage. We also describe novel interactions between POLE1 and the iron-sulfur cluster assembly complex CIA proteins CIAO1 and MMS19. We show that serine-1940 is essential for the interaction between POLE1 and MMS19, but not POLE1 and CIAO1. No defect in either proliferation or survival was identified when POLE1 serine-1940 was mutated to alanine in human cells, even following treatment with DNA damaging agents. We conclude that serine-1940 phosphorylation and the interaction between serine-1940 and MMS19 are not essential functions in the C terminal domain of the catalytic subunit of DNA polymerase ε. PMID:27235625
Tissue dissection using a 1470-nm diode laser and laparoscopic prototype
NASA Astrophysics Data System (ADS)
Chang, Chun-Hung; Hammerland, John; Nau, William H.; Fried, Nathaniel M.
2017-02-01
A continuous-wave, 40 Watt, 1470 nm laser was explored for rapid and precise dissection of porcine mesentery fascia and liver tissues, ex vivo. Laser energy was delivered through a 550-μm-core optical fiber inside a 5-mm-OD, laparoscopic probe, with detachable, 2 mm, sapphire ball rolling tip. Fascia tissue was cleanly dissected with scanning rates from 2.0 - 4.5 mm/s using 16 - 31W. Fascia collateral thermal damage measured as low as 180 +/- 50 μm at 4.5 mm/s scan speed. Porcine liver ablation crater depth measured up to 1010 +/- 220 μm with 30 W at 2.0 mm/s or as shallow as 80 +/- 30 μm with 10 W at 10 mm/s. Peak temperatures reached 130 °C at ball tip and 75 °C on metal jaws. The 1470-nm laser and probe show promise for laparoscopic tissue cutting and coagulation.
Cobalt ferrite nanocrystals: out-performing magnetotactic bacteria.
Prozorov, Tanya; Palo, Pierre; Wang, Lijun; Nilsen-Hamilton, Marit; Jones, DeAnna; Orr, Daniel; Mallapragada, Surya K; Narasimhan, Balaji; Canfield, Paul C; Prozorov, Ruslan
2007-10-01
Magnetotactic bacteria produce exquisitely ordered chains of uniform magnetite (Fe(3)O(4)) nanocrystals, and the use of the bacterial mms6 protein allows for the shape-selective synthesis of Fe(3)O(4) nanocrystals. Cobalt ferrite (CoFe(2)O(4)) nanoparticles, on the other hand, are not known to occur in living organisms. Here we report on the use of the recombinant mms6 protein in a templated synthesis of CoFe(2)O(4) nanocrystals in vitro. We have covalently attached the full-length mms6 protein and a synthetic C-terminal domain of mms6 protein to self-assembling polymers in order to template hierarchical CoFe(2)O(4) nanostructures. This new synthesis pathway enables facile room-temperature shape-specific synthesis of complex magnetic crystalline nanomaterials with particle sizes in the range of 40-100 nm that are difficult to produce using conventional techniques.
The Magnetospheric Multiscale Constellation
NASA Technical Reports Server (NTRS)
Tooley, C. R.; Black, R. K.; Robertson, B. P.; Stone, J. M.; Pope, S. E.; Davis, G. T.
2015-01-01
The Magnetospheric Multiscale (MMS) mission is the fourth mission of the Solar Terrestrial Probe (STP) program of the National Aeronautics and Space Administration (NASA). The MMS mission was launched on March 12, 2015. The MMS mission consists of four identically instrumented spin-stabilized observatories which are flown in formation to perform the first definitive study of magnetic reconnection in space. The MMS mission was presented with numerous technical challenges, including the simultaneous construction and launch of four identical large spacecraft with 100 instruments total, stringent electromagnetic cleanliness requirements, closed-loop precision maneuvering and pointing of spinning flexible spacecraft, on-board GPS based orbit determination far above the GPS constellation, and a flight dynamics design that enables formation flying with separation distances as small as 10 km. This paper describes the overall mission design and presents an overview of the design, testing, and early on-orbit operation of the spacecraft systems and instrument suite.
Magnetospheric Multiscale (MMS) Mission Attitude Ground System Design
NASA Technical Reports Server (NTRS)
Sedlak, Joseph E.; Superfin, Emil; Raymond, Juan C.
2011-01-01
This paper presents an overview of the attitude ground system (AGS) currently under development for the Magnetospheric Multiscale (MMS) mission. The primary responsibilities for the MMS AGS are definitive attitude determination, validation of the onboard attitude filter, and computation of certain parameters needed to improve maneuver performance. For these purposes, the ground support utilities include attitude and rate estimation for validation of the onboard estimates, sensor calibration, inertia tensor calibration, accelerometer bias estimation, center of mass estimation, and production of a definitive attitude history for use by the science teams. Much of the AGS functionality already exists in utilities used at NASA's Goddard Space Flight Center with support heritage from many other missions, but new utilities are being created specifically for the MMS mission, such as for the inertia tensor, accelerometer bias, and center of mass estimation. Algorithms and test results for all the major AGS subsystems are presented here.
Evidence for isoleucine as a positive effector of the ilvBN operon in Salmonella typhimurium.
Davidson, J P; Wilson, D J
1991-08-15
Concerted efforts were directed towards understanding the control of acetohydroxy acid synthase (AHAS) in the gyrB mutant hisU1820 of Salmonella typhimurium. A media shift from valine to valine plus isoleucine causes a dramatic 4 to 5 fold burst of AHAS valine sensitive activity which appears to be dependent on translation. DJ19, an isolated valine sensitive derivative of the gyrB mutant, maintains a dramatic increase in AHAS valine sensitive activity upon the addition of isoleucine to valine supplemented cultures, suggesting that the isoleucine effect is specific for valine sensitive AHAS. Evidence supports isoleucine as a positive effector on valine sensitive AHAS expression and that the gyrB mutation accentuates the isoleucine effect.
Wright, Robin; Parrish, Mark L; Cadera, Emily; Larson, Lynnelle; Matson, Clinton K; Garrett-Engele, Philip; Armour, Chris; Lum, Pek Yee; Shoemaker, Daniel D
2003-07-30
Increased levels of HMG-CoA reductase induce cell type- and isozyme-specific proliferation of the endoplasmic reticulum. In yeast, the ER proliferations induced by Hmg1p consist of nuclear-associated stacks of smooth ER membranes known as karmellae. To identify genes required for karmellae assembly, we compared the composition of populations of homozygous diploid S. cerevisiae deletion mutants following 20 generations of growth with and without karmellae. Using an initial population of 1,557 deletion mutants, 120 potential mutants were identified as a result of three independent experiments. Each experiment produced a largely non-overlapping set of potential mutants, suggesting that differences in specific growth conditions could be used to maximize the comprehensiveness of similar parallel analysis screens. Only two genes, UBC7 and YAL011W, were identified in all three experiments. Subsequent analysis of individual mutant strains confirmed that each experiment was identifying valid mutations, based on the mutant's sensitivity to elevated HMG-CoA reductase and inability to assemble normal karmellae. The largest class of HMG-CoA reductase-sensitive mutations was a subset of genes that are involved in chromatin structure and transcriptional regulation, suggesting that karmellae assembly requires changes in transcription or that the presence of karmellae may interfere with normal transcriptional regulation. Copyright 2003 John Wiley & Sons, Ltd.
Temperature-sensitive Mutants of Sindbis Virus: Biochemical Correlates of Complementation
Burge, Boyce W.; Pfefferkorn, E. R.
1967-01-01
Temperature-sensitive mutants of Sindbis virus fail to grow at a temperature that permits growth of the wild type, but when certain pairs of these mutants, mixed together, infect cells at that temperature, viral growth (i.e., complementation) occurs. The yield from this complementation, however, is of the same order of magnitude as the infectivity in the inoculum. Since in animal virus infections the protein components of the virion probably enter the cell with the viral nucleic acid, it was necessary to demonstrate that the observed complementation required synthesis of new viral protein and nucleic acid rather than some sort of rearrangement of the structural components of the inoculum. To demonstrate that complementation does require new biosynthesis, three biochemical events of normal virus growth have been observed during complementation and correlated with the efficiency of viral growth seen in complementation. These events include: (i) entrance of parental viral ribonucleic acid (RNA) into a double-stranded form; (ii) subsequent synthesis of viral RNA; and (iii) synthesis and subsequent incorporation of viral protein(s) into cell membranes where they were detected by hemadsorption. Although the infecting single-stranded RNA genome of the wild type was converted to a ribonuclease-resistant form, the genome of a mutant (ts-11) incapable of RNA synthesis at a nonpermissive temperature was not so converted. However, during complementation with another mutant also defective in viral RNA synthesis, some of the RNA of mutant ts-11 was converted to a ribonuclease-resistant form, and total synthesis of virus-specific RNA was markedly enhanced. The virus-specific alteration of the cell surface, detected by hemadsorption, was also extensively increased during complementation. These observations support the view that complementation between temperature-sensitive mutants and replication of wild-type virus are similar processes. PMID:5630228
van Beilen, Johan; Blohmke, Christoph J.; Folkerts, Hendrik; de Boer, Richard; Zakrzewska, Anna; Kulik, Wim; Vaz, Fred M.; Brul, Stanley; Ter Beek, Alexander
2016-01-01
Weak organic acids like sorbic and acetic acid are widely used to prevent growth of spoilage organisms such as Bacilli. To identify genes involved in weak acid stress tolerance we screened a transposon mutant library of Bacillus subtilis for sorbic acid sensitivity. Mutants of the rodZ (ymfM) gene were found to be hypersensitive to the lipophilic weak organic acid. RodZ is involved in determining the cell’s rod-shape and believed to interact with the bacterial actin-like MreB cytoskeleton. Since rodZ lies upstream in the genome of the essential gene pgsA (phosphatidylglycerol phosphate synthase) we hypothesized that expression of the latter might also be affected in rodZ mutants and hence contribute to the phenotype observed. We show that both genes are co-transcribed and that both the rodZ::mini-Tn10 mutant and a conditional pgsA mutant, under conditions of minimal pgsA expression, were sensitive to sorbic and acetic acid. Both strains displayed a severely altered membrane composition. Compared to the wild-type strain, phosphatidylglycerol and cardiolipin levels were lowered and the average acyl chain length was elongated. Induction of rodZ expression from a plasmid in our transposon mutant led to no recovery of weak acid susceptibility comparable to wild-type levels. However, pgsA overexpression in the same mutant partly restored sorbic acid susceptibility and fully restored acetic acid sensitivity. A construct containing both rodZ and pgsA as on the genome led to some restored growth as well. We propose that RodZ and PgsA play intertwined roles in membrane homeostasis and tolerance to weak organic acid stress. PMID:27818647
Ultrafast pulse lasers jump to macro applications
NASA Astrophysics Data System (ADS)
Griebel, Martin; Lutze, Walter; Scheller, Torsten
2016-03-01
Ultrafast Lasers have been proven for several micro applications, e.g. stent cutting, for many years. Within its development of applications Jenoptik has started to use ultrafast lasers in macro applications in the automotive industry. The JenLas D2.fs-lasers with power output control via AOM is an ideal tool for closed loop controlled material processing. Jenoptik enhanced his well established sensor controlled laser weakening process for airbag covers to a new level. The patented process enables new materials using this kind of technology. One of the most sensitive cover materials is genuine leather. As a natural product it is extremely inhomogeneous and sensitive for any type of thermal load. The combination of femtosecond pulse ablation and closed loop control by multiple sensor array opens the door to a new quality level of defined weakening. Due to the fact, that the beam is directed by scanning equipment the process can be split in multiple cycles additionally reducing the local energy input. The development used the 5W model as well as the latest 10W release of JenLas D2.fs and achieved amazing processing speeds which directly fulfilled the requirements of the automotive industry. Having in mind that the average cycle time of automotive processes is about 60s, trials had been done of processing weakening lines in genuine leather of 1.2mm thickness. Parameters had been about 15 cycles with 300mm/s respectively resulting in an average speed of 20mm/s and a cycle time even below 60s. First samples had already given into functional and aging tests and passed successfully.
Fee Comparisons of Treatments for Nonmelanoma Skin Cancer in a Private Practice Academic Setting
Wilson, Leslie S.; Pregenzer, Mark; Basu, Rituparna; Bertenthal, Daniel; Torres, Jeanette; Asgari, Maryam; Chren, Mary-Margaret
2013-01-01
OBJECTIVE To compare fees for biopsy, treatment procedure, repair, and 2-month follow-up for nonmelanoma skin cancer (NMSC) treatments: electrodesiccation and curettage (ED&C), excision, and Mohs micrographic surgery (MMS). METHODS A cost comparison of 936 primary NMSCs diagnosed in 1999/2000 at a University affiliated dermatology practice. Clinical data was from medical record review. 2007 Medicare Fee Schedule costs determined fees for surgical care. Pearson chi-square tests, t-tests and analysis of variance compared fee differences. Linear regression determined independent effects of tumor and treatment characteristics on fees. RESULTS Mean fees/lesion were $463 for ED&C, $1,222 for excision, and $2,085 for MMS (p < .001). For all treatments, primary procedure costs were highest (38%, 45%, and 41%). Total repair fees were higher with MMS ($735) vs excisions ($197). Fees were higher for head and neck tumors (p < .001), H-zone tumors (p < .001), and tumors smaller than 10 mm in diameter (p = .04). Regression models predicted that the treatment fees would be $2,109 for MMS and $1,252 for excision (p < .001). Tumor size greater than 10 mm in diameter (added $128), tumors on the head and neck (added $966), and MMS (added $857 vs excision) were independently related to higher fees (p < .001). CONCLUSION Even after adjusting for risk factors, MMS has higher fees than excision for primary NMSC. Repairs accounted for the majority of this difference. These fee comparisons provide a basis for comparative effectiveness studies of treatments for this common cancer. PMID:22145798
Hu, Changmin; Liu, Shen; Zhang, Yang; Li, Bin; Yang, Huilin; Fan, Cunyi; Cui, Wenguo
2013-07-01
Physical barriers such as electrospun fibrous membranes are potentially useful in preventing peritendinous adhesions after surgery. However, inflammatory responses caused by degradation of barrier materials remain a major challenge. This study aimed to fabricate electrospun composite fibrous membranes based on drug-loaded modified mesoporous silica (MMS) and poly (l-lactic acid) (PLLA). Using a co-solvent-based electrospinning method ibuprofen (IBU)-loaded MMS was successfully and uniformly encapsulated in the PLLA fibers. The electrospun PLLA-MMS-IBU composite fibrous membranes showed significantly lower initial burst release (6% release in the first 12h) compared with that of electrospun PLLA-IBU fibrous membranes (46% release in the first 12h) in in vitro release tests. Moreover, the release from PLLA-MMS-IBU was also for significantly longer than that from PLLA-IBU (100 vs. 20days). In animal studies both PLLA-IBU and PLLA-MMS-IBU showed improved anti-adhesion properties and anti-inflammatory effects compared with PLLA fibrous membrane alone 4weeks after implantation. Further, animals implanted with PLLA-MMS-IBU for 8weeks showed the lowest inflammation and best recovery compared with those implanted with PLLA-IBU and PLLA, most likely as a result of its long-term IBU release profile. Therefore, this study provides a platform technique for fabricating fibrous membranes with long-term sustained drug release characteristics which may function as a novel carrier for long-term anti-inflammation and anti-adhesion to prevent peritendinous adhesions. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
30 CFR 285.215 - What areas will MMS offer in a lease sale?
Code of Federal Regulations, 2010 CFR
2010-07-01
... RENEWABLE ENERGY ALTERNATE USES OF EXISTING FACILITIES ON THE OUTER CONTINENTAL SHELF Issuance of OCS Renewable Energy Leases Competitive Lease Process § 285.215 What areas will MMS offer in a lease sale? The...
30 CFR 203.82 - What is MMS's authority to collect this information?
Code of Federal Regulations, 2011 CFR
2011-07-01
... Oil, Gas, and Sulfur General Required Reports § 203.82 What is MMS's authority to collect this...) Applicants (respondents) are Federal OCS oil and gas lessees. Applications are required to obtain or retain a...
30 CFR 204.205 - How do I obtain accounting and auditing relief?
Code of Federal Regulations, 2010 CFR
2010-07-01
..., address, phone number, and contact name; and (ii) The specific MMS lease number and agreement number, if... contain: (i) Your company name, MMS-assigned payor code, address, phone number, and contact name; (ii) The...
Publications - GMC 203 | Alaska Division of Geological & Geophysical
DGGS GMC 203 Publication Details Title: A summary of the data resulting from the 1991 MMS geologic Turner, Ron, and Core Laboratories, 1992, A summary of the data resulting from the 1991 MMS geologic
30 CFR 210.53 - When are my royalty reports and payments due?
Code of Federal Regulations, 2010 CFR
2010-07-01
... When are my royalty reports and payments due? (a) Completed Forms MMS-2014 for royalty payments and the...) Completed Forms MMS-2014 for rental payments, where applicable, and the associated payments are due as...
30 CFR 285.436 - Can MMS require lease or grant contraction?
Code of Federal Regulations, 2011 CFR
2011-07-01
... manage activities in a manner that is consistent with the provisions of this part. The MMS will notify... present orally or in writing information demonstrating that you need the area in question to manage lease...
Tsujimoto; Shigeyama; Yoshii
2000-03-01
We suggest that if the astrophysical site for r-process nucleosynthesis in the early Galaxy is confined to a narrow mass range of Type II supernova (SN II) progenitors, with a lower mass limit of Mms=20 M middle dot in circle, a unique feature in the observed distribution of [Ba/Mg] versus [Mg/H] for extremely metal-poor stars can be adequately reproduced. We associate this feature, a bifurcation of the observed elemental ratios into two branches in the Mg abundance interval -3.7=&sqbl0;Mg&solm0;H&sqbr0;=-2.3, with two distinct processes. The first branch, which we call the y-branch, is associated with the production of Ba and Mg from individual massive supernovae. The derived mass of Ba synthesized in SNe II is 8.5x10-6 M middle dot in circle for Mms=20 M middle dot in circle and 4.5x10-8 M middle dot in circle for Mms=25 M middle dot in circle. We conclude that SNe II with Mms approximately 20 M middle dot in circle are the dominant source of r-process nucleosynthesis in the early Galaxy. An SN-induced chemical evolution model with this Mms-dependent Ba yield creates the y-branch, reflecting the different nucleosynthesis yields of [Ba/Mg] for each SN II with Mms greater, similar20 M middle dot in circle. The second branch, which we call the i-branch, is associated with the elemental abundance ratios of stars which were formed in the dense shells of the interstellar medium swept up by SNe II with Mms<20 M middle dot in circle that do not synthesize r-process elements, and it applies to stars with observed Mg abundances in the range &sqbl0;Mg&solm0;H&sqbr0;<-2.7. The Ba abundances in these stars reflect those of the interstellar gas at the (later) time of their formation. The existence of a [Ba/Mg] i-branch strongly suggests that SNe II that are associated with stars of progenitor mass Mms=20 M middle dot in circle are infertile sources for the production of r-process elements. We predict the existence of this i-branch for other r-process elements, such as europium (Eu), to the extent that their production site is in common with Ba.
A MUTANT OF YEAST APPARENTLY DEFECTIVE IN THE INITIATION OF PROTEIN SYNTHESIS*
Hartwell, Leland H.; McLaughlin, Calvin S.
1969-01-01
A temperature-sensitive mutant of yeast, ts-187, which is apparently unable to initiate the synthesis of new polypeptide chains after a short incubation at the restrictive temperature, is described. The existence of this mutant demonstrates that in eucaryotic cells, as in procaryotic cells, there are processes unique to the initiation of polypeptide chains. PMID:5256225
Mahoney, C L; Choudhury, B; Davies, H; Edkins, S; Greenman, C; Haaften, G van; Mironenko, T; Santarius, T; Stevens, C; Stratton, M R; Futreal, P A
2009-01-27
LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies.
Mahoney, C L; Choudhury, B; Davies, H; Edkins, S; Greenman, C; Haaften, G van; Mironenko, T; Santarius, T; Stevens, C; Stratton, M R; Futreal, P A
2009-01-01
LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies. PMID:19165201
Kumar, M. Nagaraj; Jane, Wann-Neng; Verslues, Paul E.
2013-01-01
The molecular basis of plant osmosensing remains unknown. Arabidopsis (Arabidopsis thaliana) Histidine Kinase1 (AHK1) can complement the osmosensitivity of yeast (Saccharomyces cerevisiae) osmosensor mutants lacking Synthetic Lethal of N-end rule1 and SH3-containing Osmosensor and has been proposed to act as a plant osmosensor. We found that ahk1 mutants in either the Arabidopsis Nossen-0 or Columbia-0 background had increased stomatal density and stomatal index consistent with greater transpirational water loss. However, the growth of ahk1 mutants was not more sensitive to controlled moderate low water potential (ψw) or to salt stress. Also, ahk1 mutants had increased, rather than reduced, solute accumulation across a range of low ψw severities. ahk1 mutants had reduced low ψw induction of Δ1-Pyrroline-5-Carboxylate Synthetase1 (P5CS1) and 9-cis-Epoxycarotenoid Dioxygenase3, which encode rate-limiting enzymes in proline and abscisic acid (ABA) synthesis, respectively. However, neither Pro nor ABA accumulation was reduced in ahk1 mutants at low ψw. P5CS1 protein level was not reduced in ahk1 mutants. This indicated that proline accumulation was regulated in part by posttranscriptional control of P5CS1 that was not affected by AHK1. Expression of AHK1 itself was reduced by low ψw, in contrast to previous reports. These results define a role of AHK1 in controlling stomatal density and the transcription of stress-responsive genes. These phenotypes may be mediated in part by reduced ABA sensitivity. More rapid transpiration and water depletion can also explain the previously reported sensitivity of ahk1 to uncontrolled soil drying. The unimpaired growth, ABA, proline, and solute accumulation of ahk1 mutants at low ψw suggest that AHK1 may not be the main plant osmosensor required for low ψw tolerance. PMID:23184230
Coulter-Mackie, M B; Lian, Q
2008-07-01
Alanine:glyoxylate aminotransferase (AGT) is a liver peroxisomal enzyme whose deficiency results in primary hyperoxaluria type 1 (PH1). More than 75 PH1 mutations are now documented in the AGT gene (AGXT), of which about 50% are missense. We have previously demonstrated that many such mutants expressed by transcription/translation are subject to generalized degradation by the proteasome and a specific limited trimming by an endogenous ATP-independent protease activity. Here, we report the results of partial digestion using trypsin as a mimic for the endogenous non-proteasomal protease and the use of N-terminal protein sequencing to determine the sensitive site. Partial trypsin digestion also provided an indicator of proper folding of the mutant enzyme. For selected mutations the sensitivity to trypsin could be ameliorated by addition of pyridoxal phosphate or aminooxy acetic acid as specific pharmacological chaperones.
CAPILLARY CONDENSATION IN MMS AND PORE STRUCTURE CHARACTERIZATION. (R825959)
Phenomena of capillary condensation and desorption in siliceous mesoporous molecular sieves (MMS) with cylindrical channels are studied by means of the non-local density functional theory (NLDFT). The results are compared with macroscopic thermodynamic approaches based on Kelv...
Commissioning MMS: Challenges and Lessons Learned
NASA Technical Reports Server (NTRS)
Wood, Paul; Gramling, Cheryl; Reiter, Jennifer; Smith, Patrick; Stone, John
2016-01-01
This paper discusses commissioning of NASA's Magnetospheric MultiScale (MMS) Mission. The mission includes four identical spacecraft with a large, complex set of instrumentation. The planning for and execution of commissioning for this mission is described. The paper concludes by discussing lessons learned.
30 CFR 291.108 - How do I pay the processing fee?
Code of Federal Regulations, 2010 CFR
2010-07-01
... Web site may be accessed through links on the MMS Offshore Web site at: http://www.mms.gov/offshore/homepage (on drop-down topic list) or directly through Pay.Gov at: https://www.pay.gov/paygov/. (b) You...
NASA Technical Reports Server (NTRS)
Adams, Mitzi
2014-01-01
Two Dual Ion Spectrometer flight units of the Fast Plasma Instrument Suite (FPI) for the Magnetospheric Multiscale Mission (MMS) have returned to MSFC for flight testing. Anticipated to begin on June 30, tests will ensue in the Low Energy Electron and Ion Facility of the Heliophysics and Planetary Science Office (ZP13), managed by Dr. Victoria Coffey of the Natural Environments Branch of the Engineering Directorate (EV44). The MMS mission consists of four identical spacecraft, whose purpose is to study magnetic reconnection in the boundary regions of Earth's magnetosphere.
Bedogni, Giorgio; Biasini, Beatrice; Zavaroni, Ivana; Ventura, Marco; Galli, Daniela; Mirandola, Prisco; Vitale, Marco; Bonadonna, Riccardo C.; Passeri, Giovanni
2018-01-01
Adequate visual function has a strong impact on the quality of life of people. Several foods and food components have been hypothesized to play a role in the maintenance of normal visual function and in the prevention of eye diseases. Some of these foods/food components have been the object of a request of authorization for use of health claims under Articles 13(5) or 14 of the Regulation (EC) 1924/2006. Most of these requests have received a negative opinion from the European Food Safety Authority (EFSA) due to the choice of inappropriate outcome variables (OVs) and/or methods of measurement (MMs) applied in the studies used to substantiate the claims. This manuscript refers to the collection, collation and critical analysis of OVs and MMs related to vision. Guidance document and requests for authorization of health claims were used to collect OVs and MMs related to vision. A literature review was performed to critically analyse OVs and MMs, with the aim of defining their appropriateness in the context of a specific claimed effect related to vision. The results highlight the importance of adequate choices of OVs and MMs for an effective substantiation of claims related to visual function. PMID:29443929
Hawkins, Spencer D; Koch, Sarah B; Williford, Phillip M; Feldman, Steven R; Pearce, Daniel J
2018-07-01
Consent and wound care (WC) videos are used for education in Mohs micrographic surgery (MMS). Postoperative text messaging is poorly studied. Develop and evaluate perioperative resources for MMS patients-video modules (DermPatientEd.com) and postoperative text messaging (DermTexts.com). A study was conducted on 90 MMS patients. Patients were randomized 1:1:1:1 to videos with text messages, videos-only, text messages-only, or control. Primary outcomes included preoperative anxiety and knowledge of MMS and postoperative care. The secondary outcome included helpfulness/preference of interventions. Patients experienced a 19% reduction in anxiety as measured by a visual analog scale after the MMS video (p = .00062). There was no difference in knowledge after the WC video (p = .21498). Patients were more likely to report the WC video "very helpful" when compared with the pamphlet in understanding postoperative WC (p = .0016). Patients in text messaging groups were not more likely to report the service as "very helpful" when compared with the pamphlet (p = .3566), but preferred to receive WC instructions by text message for future visits (p = .0001). These resources proved helpful and effective in reducing preoperative anxiety. Patients prefer text message-based WC instructions over pamphlets after experiencing the service, but do not find them more helpful.
Cortelazzi, Chiara; Zavaroni, Ivana; Bedogni, Giorgio; Musci, Marilena; Pruneti, Carlo; Passeri, Giovanni; Ventura, Marco; Galli, Daniela; Vitale, Marco; Bonadonna, Riccardo C.; Di Nuzzo, Sergio; De Felici, Maria Beatrice
2017-01-01
Evidence suggests a protective role for several nutrients and foods in the maintenance of skin function. Nevertheless, all the requests for authorization to use health claims under Article 13(5) in the framework of maintenance of skin function presented to the European Food Safety Authority (EFSA) have received a negative opinion. Reasons for such failures are mainly due to an insufficient substantiation of the claimed effects, including the choice of inappropriate outcome variables (OVs) and methods of measurement (MMs). The present paper reports the results of an investigation aimed at collecting, collating and critically analyzing the information with relation to claimed effects (CEs), OVs and MMs related to skin health compliance with Regulation 1924/2006. CEs, OVs and MMs were collected from both the EFSA Guidance document and from the authorization requests of health claims under Article 13(5). The critical analysis of OVs and MMs was based on a literature review, and was aimed at defining their appropriateness (alone or in combination with others) in the context of a specific CE. The results highlight the importance of an adequate choice of OVs and MMs for an effective substantiation of the claims. PMID:29271939
He, Dawei; Dong, Wei; Tang, Songchao; Wei, Jie; Liu, Zhenghui; Gu, Xiaojiang; Li, Ming; Guo, Han; Niu, Yunfei
2014-06-01
Mesoporous magnesium silicate (m-MS) and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) composite scaffolds were fabricated by solvent-casting and particulate leaching method. The results suggested that the incorporation of m-MS into PCL-PEG-PCL could significantly improve the water adsorption of the m-MS/PCL-PEG-PCL composite (m-MPC) scaffolds. The in vitro degradation behavior of m-MPC scaffolds were determined by testing weight loss of the scaffolds after soaking into phosphate buffered saline (PBS), and the result showed that the degradation of m-MPC scaffolds was obviously enhanced by addition of m-MS into PCL-PEG-PCL after soaking for 10 weeks. Proliferation of MG63 cells on m-MPC was significantly higher than MPC scaffolds at 4 and 7 days. ALP activity on the m-MPC was obviously higher than MPC scaffolds at 7 days, revealing that m-MPC could promote cell differentiation. Histological evaluation showed that the introduction of m-MS into PCL-PEG-PCL enhanced the efficiency of new bone formation when the m-MPC scaffolds implanted into bone defect of rabbits. The results suggested that the inorganic/organic composite of m-MS and PCL-PEG-PCL scaffolds exhibited good biocompatibility, degradability and osteogenesis.
Serra-Guillén, C; Llombart, B; Nagore, E; Guillén, C; Requena, C; Traves, V; Kindem, S; Alcalá, R; Rivas, N; Sanmartín, O
2015-01-01
Dermatofibrosarcoma protuberans (DFSP) is an uncommon skin tumour with aggressive local growth. Whether DFSP should be treated with conventional surgery (CS) or Mohs micrographic surgery (MMS) has long been a topic of debate. To calculate, in a large series of DFSP treated by MMS, the minimum margin that would have been needed to achieve complete clearance by CS. Secondly, to calculate the percentage of healthy tissue that was preserved by MMS rather than CS with 2- and 3-cm margins. The minimum margin was calculated by measuring the largest distance from the visible edge of the tumour to the edge of the definitive surgical defect. Tumour and surgical defect areas for hypothetical CS with 2- and 3-cm margins were calculated using AutoCAD for Windows. A mean minimum margin of 1·34 cm was required to achieve complete clearance for the 74 tumours analysed. The mean percentages of skin spared using MMS rather than CS with 2- and 3-cm margins were 49·4% and 67·9%, respectively. MMS can achieve tumour clearance with smaller margins and greater preservation of healthy tissue than CS. © 2014 British Association of Dermatologists.
Characteristics of Energetic Particle Acceleration in Hot Flow Anomalies Observed by MMS
NASA Astrophysics Data System (ADS)
Turner, D. L.; Schwartz, S. J.; Wilson, L. B., III; Liu, T. Z.; Osmane, A.; Fennell, J. F.; Blake, J. B.; Jaynes, A. N.; Goodrich, K.; Mauk, B.; Gershman, D. J.; Avanov, L. A.; Strangeway, R. J.; Torbert, R. B.; Burch, J. L.; Leonard, T. W.
2017-12-01
During its orbital transits with apogees on Earth's dayside, NASA's Magnetospheric Multiscale (MMS) mission captured high resolution observations from several transient ion foreshock phenomena, including multiple hot flow anomalies (HFAs). With MMS' four identically instrumented spacecraft, those events offer unprecedented multipoint observations and resolution of plasma, energetic particles, and electric and magnetic fields and waves within and around HFAs. In this presentation, we compare and contrast the geometries and characteristics of fully-developed HFAs observed by MMS in the interest of determining which HFAs are most efficient at accelerating energetic particles (i.e. >1 to 100s of keV electrons, protons, and heavy ions) and how those HFAs may do so. In particular, we focus on: 1) the orientation of the fast magnetosonic shocks and wave activity that form at the upstream edge of HFAs and 2) how the unique structures and activity characteristic of HFAs may result in enhanced acceleration of energetic particles via shock acceleration processes and shock-shock interactions between the HFA shock and Earth's bow shock. The results of this study are of interest to previous studies of foreshock transients from missions such as THEMIS and Cluster, are relevant to the dayside science objectives of the MMS extended mission, and may have implications for energetic particle acceleration at other astrophysical shocks throughout the Universe.
Magnetospheric Multiscale Mission (MMS) Phase 2B Navigation Performance
NASA Technical Reports Server (NTRS)
Scaperoth, Paige Thomas; Long, Anne; Carpenter, Russell
2009-01-01
The Magnetospheric Multiscale (MMS) formation flying mission, which consists of four spacecraft flying in a tetrahedral formation, has challenging navigation requirements associated with determining and maintaining the relative separations required to meet the science requirements. The baseline navigation concept for MMS is for each spacecraft to independently estimate its position, velocity and clock states using GPS pseudorange data provided by the Goddard Space Flight Center-developed Navigator receiver and maneuver acceleration measurements provided by the spacecraft's attitude control subsystem. State estimation is performed onboard in real-time using the Goddard Enhanced Onboard Navigation System flight software, which is embedded in the Navigator receiver. The current concept of operations for formation maintenance consists of a sequence of two maintenance maneuvers that is performed every 2 weeks. Phase 2b of the MMS mission, in which the spacecraft are in 1.2 x 25 Earth radii orbits with nominal separations at apogee ranging from 30 km to 400 km, has the most challenging navigation requirements because, during this phase, GPS signal acquisition is restricted to less than one day of the 2.8-day orbit. This paper summarizes the results from high-fidelity simulations to determine if the MMS navigation requirements can be met between and immediately following the maintenance maneuver sequence in Phase 2b.
Martini, Daniela; Angelino, Donato; Cortelazzi, Chiara; Zavaroni, Ivana; Bedogni, Giorgio; Musci, Marilena; Pruneti, Carlo; Passeri, Giovanni; Ventura, Marco; Galli, Daniela; Mirandola, Prisco; Vitale, Marco; Dei Cas, Alessandra; Bonadonna, Riccardo C; Di Nuzzo, Sergio; De Felici, Maria Beatrice; Del Rio, Daniele
2017-12-22
Evidence suggests a protective role for several nutrients and foods in the maintenance of skin function. Nevertheless, all the requests for authorization to use health claims under Article 13(5) in the framework of maintenance of skin function presented to the European Food Safety Authority (EFSA) have received a negative opinion. Reasons for such failures are mainly due to an insufficient substantiation of the claimed effects, including the choice of inappropriate outcome variables (OVs) and methods of measurement (MMs). The present paper reports the results of an investigation aimed at collecting, collating and critically analyzing the information with relation to claimed effects (CEs), OVs and MMs related to skin health compliance with Regulation 1924/2006. CEs, OVs and MMs were collected from both the EFSA Guidance document and from the authorization requests of health claims under Article 13(5). The critical analysis of OVs and MMs was based on a literature review, and was aimed at defining their appropriateness (alone or in combination with others) in the context of a specific CE. The results highlight the importance of an adequate choice of OVs and MMs for an effective substantiation of the claims.
Martini, Daniela; Innocenti, Augusto; Cosentino, Chiara; Bedogni, Giorgio; Angelino, Donato; Biasini, Beatrice; Zavaroni, Ivana; Ventura, Marco; Galli, Daniela; Mirandola, Prisco; Vitale, Marco; Dei Cas, Alessandra; Bonadonna, Riccardo C; Passeri, Giovanni; Pruneti, Carlo; Del Rio, Daniele
2018-02-14
Adequate visual function has a strong impact on the quality of life of people. Several foods and food components have been hypothesized to play a role in the maintenance of normal visual function and in the prevention of eye diseases. Some of these foods/food components have been the object of a request of authorization for use of health claims under Articles 13(5) or 14 of the Regulation (EC) 1924/2006. Most of these requests have received a negative opinion from the European Food Safety Authority (EFSA) due to the choice of inappropriate outcome variables (OVs) and/or methods of measurement (MMs) applied in the studies used to substantiate the claims. This manuscript refers to the collection, collation and critical analysis of OVs and MMs related to vision. Guidance document and requests for authorization of health claims were used to collect OVs and MMs related to vision. A literature review was performed to critically analyse OVs and MMs, with the aim of defining their appropriateness in the context of a specific claimed effect related to vision. The results highlight the importance of adequate choices of OVs and MMs for an effective substantiation of claims related to visual function.
Pds5 regulators segregate cohesion and condensation pathways in Saccharomyces cerevisiae
Tong, Kevin; Skibbens, Robert V.
2015-01-01
Cohesins are required both for the tethering together of sister chromatids (termed cohesion) and subsequent condensation into discrete structures—processes fundamental for faithful chromosome segregation into daughter cells. Differentiating between cohesin roles in cohesion and condensation would provide an important advance in studying chromatin metabolism. Pds5 is a cohesin-associated factor that is essential for both cohesion maintenance and condensation. Recent studies revealed that ELG1 deletion suppresses the temperature sensitivity of pds5 mutant cells. However, the mechanisms through which Elg1 may regulate cohesion and condensation remain unknown. Here, we report that ELG1 deletion from pds5-1 mutant cells results in a significant rescue of cohesion, but not condensation, defects. Based on evidence that Elg1 unloads the DNA replication clamp PCNA from DNA, we tested whether PCNA overexpression would similarly rescue pds5-1 mutant cell cohesion defects. The results indeed reveal that elevated levels of PCNA rescue pds5-1 temperature sensitivity and cohesion defects, but do not rescue pds5-1 mutant cell condensation defects. In contrast, RAD61 deletion rescues the condensation defect, but importantly, neither the temperature sensitivity nor cohesion defects exhibited by pds5-1 mutant cells. In combination, these findings reveal that cohesion and condensation are separable pathways and regulated in nonredundant mechanisms. These results are discussed in terms of a new model through which cohesion and condensation are spatially regulated. PMID:25986377
Pds5 regulators segregate cohesion and condensation pathways in Saccharomyces cerevisiae.
Tong, Kevin; Skibbens, Robert V
2015-06-02
Cohesins are required both for the tethering together of sister chromatids (termed cohesion) and subsequent condensation into discrete structures-processes fundamental for faithful chromosome segregation into daughter cells. Differentiating between cohesin roles in cohesion and condensation would provide an important advance in studying chromatin metabolism. Pds5 is a cohesin-associated factor that is essential for both cohesion maintenance and condensation. Recent studies revealed that ELG1 deletion suppresses the temperature sensitivity of pds5 mutant cells. However, the mechanisms through which Elg1 may regulate cohesion and condensation remain unknown. Here, we report that ELG1 deletion from pds5-1 mutant cells results in a significant rescue of cohesion, but not condensation, defects. Based on evidence that Elg1 unloads the DNA replication clamp PCNA from DNA, we tested whether PCNA overexpression would similarly rescue pds5-1 mutant cell cohesion defects. The results indeed reveal that elevated levels of PCNA rescue pds5-1 temperature sensitivity and cohesion defects, but do not rescue pds5-1 mutant cell condensation defects. In contrast, RAD61 deletion rescues the condensation defect, but importantly, neither the temperature sensitivity nor cohesion defects exhibited by pds5-1 mutant cells. In combination, these findings reveal that cohesion and condensation are separable pathways and regulated in nonredundant mechanisms. These results are discussed in terms of a new model through which cohesion and condensation are spatially regulated.
Fournier, Marjorie; Zhang, Yi; Wildschut, Janine D.; Dolla, Alain; Voordouw, Johanna K.; Schriemer, David C.; Voordouw, Gerrit
2003-01-01
Two mutant strains of Desulfovibrio vulgaris Hildenborough lacking either the sod gene for periplasmic superoxide dismutase or the rbr gene for rubrerythrin, a cytoplasmic hydrogen peroxide (H2O2) reductase, were constructed. Their resistance to oxidative stress was compared to that of the wild-type and of a sor mutant lacking the gene for the cytoplasmic superoxide reductase. The sor mutant was more sensitive to exposure to air or to internally or externally generated superoxide than was the sod mutant, which was in turn more sensitive than the wild-type strain. No obvious oxidative stress phenotype was found for the rbr mutant, indicating that H2O2 resistance may also be conferred by two other rbr genes in the D. vulgaris genome. Inhibition of Sod activity by azide and H2O2, but not by cyanide, indicated it to be an iron-containing Sod. The positions of Fe-Sod and Sor were mapped by two-dimensional gel electrophoresis (2DE). A strong decrease of Sor in continuously aerated cells, indicated by 2DE, may be a critical factor in causing cell death of D. vulgaris. Thus, Sor plays a key role in oxygen defense of D. vulgaris under fully aerobic conditions, when superoxide is generated mostly in the cytoplasm. Fe-Sod may be more important under microaerophilic conditions, when the periplasm contains oxygen-sensitive, superoxide-producing targets. PMID:12486042
Arabidopsis MLO2 is a negative regulator of sensitivity to extracellular reactive oxygen species.
Cui, Fuqiang; Wu, Hongpo; Safronov, Omid; Zhang, Panpan; Kumar, Rajeev; Kollist, Hannes; Salojärvi, Jarkko; Panstruga, Ralph; Overmyer, Kirk
2018-04-01
The atmospheric pollutant ozone (O 3 ) is a strong oxidant that causes extracellular reactive oxygen species (ROS) formation, has significant ecological relevance, and is used here as a non-invasive ROS inducer to study plant signalling. Previous genetic screens identified several mutants exhibiting enhanced O 3 sensitivity, but few with enhanced tolerance. We found that loss-of-function mutants in Arabidopsis MLO2, a gene implicated in susceptibility to powdery mildew disease, exhibit enhanced dose-dependent tolerance to O 3 and extracellular ROS, but a normal response to intracellular ROS. This phenotype is increased in a mlo2 mlo6 mlo12 triple mutant, reminiscent of the genetic redundancy of MLO genes in powdery mildew resistance. Stomatal assays revealed that enhanced O 3 tolerance in mlo2 mutants is not caused by altered stomatal conductance. We explored modulation of the mlo2-associated O 3 tolerance, powdery mildew resistance, and early senescence phenotypes by genetic epistasis analysis, involving mutants with known effects on ROS sensitivity or antifungal defence. Mining of publicly accessible microarray data suggests that these MLO proteins regulate accumulation of abiotic stress response transcripts, and transcript accumulation of MLO2 itself is O 3 responsive. In summary, our data reveal MLO2 as a novel negative regulator in plant ROS responses, which links biotic and abiotic stress response pathways. © 2018 John Wiley & Sons Ltd.
Chenevert, J M; Naumovski, L; Schultz, R A; Friedberg, E C
1986-04-01
The denV gene of bacteriophage T4 was reconstituted from two overlapping DNA fragments cloned in M13 vectors. The coding region of the intact gene was tailored into a series of plasmid vectors containing different promoters suitable for expression of the gene in E. coli and in yeast. Induction of the TAC promoter with IPTG resulted in overexpression of the gene, which was lethal to E. coli. Expression of the TACdenV gene in the absence of IPTG, or the use of the yeast GAL1 or ADH promoters resulted in partial complementation of the UV sensitivity of uvrA, uvrB, uvrC and recA mutants of E. coli and rad1, rad2, rad3, rad4 and rad10 mutants of S. cerevisiae. The extent of denV-mediated reactivation of excision-defective mutants was approximately equal to that of photoreactivation of such strains. Excision proficient E. coli cells transformed with a plasmid containing the denV gene were slightly more resistant to ultraviolet (UV) radiation than control cells without the denV gene. On the other hand, excision proficient yeast cells were slightly more sensitive to killing by UV radiation following transformation with a plasmid containing the denV gene. This effect was more pronounced in yeast mutants of the RAD52 epistasis group.
Regulation of drought tolerance by the F-box protein MAX2 in Arabidopsis.
Bu, Qingyun; Lv, Tianxiao; Shen, Hui; Luong, Phi; Wang, Jimmy; Wang, Zhenyu; Huang, Zhigang; Xiao, Langtao; Engineer, Cawas; Kim, Tae Houn; Schroeder, Julian I; Huq, Enamul
2014-01-01
MAX2 (for MORE AXILLARY GROWTH2) has been shown to regulate diverse biological processes, including plant architecture, photomorphogenesis, senescence, and karrikin signaling. Although karrikin is a smoke-derived abiotic signal, a role for MAX2 in abiotic stress response pathways is least investigated. Here, we show that the max2 mutant is strongly hypersensitive to drought stress compared with wild-type Arabidopsis (Arabidopsis thaliana). Stomatal closure of max2 was less sensitive to abscisic acid (ABA) than that of the wild type. Cuticle thickness of max2 was significantly thinner than that of the wild type. Both of these phenotypes of max2 mutant plants correlate with the increased water loss and drought-sensitive phenotype. Quantitative real-time reverse transcription-polymerase chain reaction analyses showed that the expression of stress-responsive genes and ABA biosynthesis, catabolism, transport, and signaling genes was impaired in max2 compared with wild-type seedlings in response to drought stress. Double mutant analysis of max2 with the ABA-insensitive mutants abi3 and abi5 indicated that MAX2 may function upstream of these genes. The expression of ABA-regulated genes was enhanced in imbibed max2 seeds. In addition, max2 mutant seedlings were hypersensitive to ABA and osmotic stress, including NaCl, mannitol, and glucose. Interestingly, ABA, osmotic stress, and drought-sensitive phenotypes were restricted to max2, and the strigolactone biosynthetic pathway mutants max1, max3, and max4 did not display any defects in these responses. Taken together, these results uncover an important role for MAX2 in plant responses to abiotic stress conditions.
White, W. H.; Johnson, D. I.
1997-01-01
Cdc24p is the guanine-nucleotide exchange factor for the Cdc42p GTPase, which controls cell polarity in Saccharomyces cerevisiae. To identify new genes that may affect cell polarity, we characterized six UV-induced csl (CDC24 synthetic-lethal) mutants that exhibited synthetic-lethality with cdc24-4(ts) at 23°. Five mutants were not complemented by plasmid-borne CDC42, RSR1, BUD5, BEM1, BEM2, BEM3 or CLA4 genes, which are known to play a role in cell polarity. The csl3 mutant displayed phenotypes similar to those observed with calcium-sensitive, Pet(-) vma mutants defective in vacuole function. CSL5 was allelic to VMA5, the vacuolar H(+)-ATPase subunit C, and one third of csl5 cdc24-4(ts) cells were elongated or had misshapen buds. A cdc24-4(ts) Δvma5::LEU2 double mutant did not exhibit synthetic lethality, suggesting that the csl5/vma5 cdc24-4(ts) synthetic-lethality was not simply due to altered vacuole function. The cdc24-4(ts) mutant, like Δvma5::LEU2 and csl3 mutants, was sensitive to high levels of Ca(2+) as well as Na(+) in the growth media, which did not appear to be a result of a fragile cell wall because the phenotypes were not remedied by 1 M sorbitol. Our results indicated that Cdc24p was required in one V-ATPase mutant and another mutant affecting vacuole morphology, and also implicated Cdc24p in Na(+) tolerance. PMID:9286667