Low work-function coating for an entirely propellantless bare electrodynamic tether

We present the possibility of a low work-function material, calcium aluminate electride, being used for a coating on a bare electrodynamic tether system. Analyses suggest that the coating would eliminate the need for an active cathodic device like a hollow cathode and, consequently, eliminate the need for an expellant to the hollow cathode, thus resulting in an electrodynamic tether system that requires no consumables. Applications include on-orbit power generation and deorbiting debris from low Earth orbit in a simple and trouble-free manner.

Propellantless de orbiting of space debris by bare electrodynamic tethers

A 3-year Project started on November 1 2010, financed by the European Commision within the FP-7 Space Program, and aimed at developing an efficient de-orbit system that could be carried on board by future spacecraft launched into LEO, will be presented. The operational system will deploy a thin uninsulated tape-tether to collect electrons as a giant Langmuir probe, using no propellant/no power supply, and generating power on board. This project will involve free-fall tests, and laboratory hypervelocity-impact and tether-current tests, and design/Manufacturing of subsystems: interface elements, electric control and driving module, electron-ejecting plasma contactor, tether-deployment mechanism/end-mass, and tape samples. Preliminary results to be presented involve: i) devising criteria for sizing the three disparate tape dimensions, affecting mass, resistance, current-collection, magnetic self-field, and survivability against debris itself; ii) assessing the dynamical relevance of tether parameters in implementing control laws to limit oscillations in /off the orbital plane, where passive stability may be marginal; iii) deriving a law for bare-tape current from numerical simulations and chamber tests, taking into account ambient magnetic field, ion ram motion, and adiabatic electron trapping; iv) determining requirements on a year-dormant hollow cathode under long times/broad emission-range operation, and trading-off against use of electron thermal emission; v) determining requirements on magnetic components and power semiconductors for a control module that faces high voltage/power operation under mass/volume limitations; vi) assessing strategies to passively deploy a wide conductive tape that needs no retrieval, while avoiding jamming and ending at minimum libration; vii) evaluating the tape structure as regards conductive and dielectric materials, both lengthwise and in its cross-section, in particular to prevent arcing in triple-point junctions.

BETs: Propellant less de orbiting of space debris by bare electrodynamic tethers

As a fundamental contribution to limiting the increase of debris in the Space environment, a three-year project started on 1 November 2010 financed by the European Commission under the FP-7 Space Programme. It aims at developing a universal system to be carried on board future satellites launched into low Earth orbit (LEO), to allow de-orbiting at end of life. The operational system involves a conductive tape-tether left bare of insulation to establish anodic contact with the ambient plasma as a giant Langmuir probe. The project will size the three disparate dimensions of a tape for a selected de-orbit mission and determine scaling laws to allow system design for a general mission. It will implement control laws to restrain tether dynamics in/off the orbital plane; and will carry out plasma chamber measurements and numerical simulations of tether-plasma interaction. The project also involves the design and manufacturing of subsystems: electron-ejecting plasma contactors, an electric control and power module, interface elements, tether and deployment mechanisms, tether tape/end-mass as well as current collection plus free-fall, and hypervelocity impact tests.

An universal system to de-orbit satellites at end of life

A 3-year Project financed by the European Commission is aimed at developing a universal system to de-orbit satellites at their end of life, as a fundamental contribution to limit the increase of debris in the Space environment. The operational system involves a conductive tapetether left bare to establish anodic contact with the ambient plasma as a giant Langmuir probe. The Project will size the three disparate dimensions of a tape for a selected de-orbit mission and determine scaling laws to allow system design for a general mission. Starting at the second year, mission selection is carried out while developing numerical codes to implement control laws on tether dynamics in/off the orbital plane; performing numerical simulations and plasma chamber measurements on tether-plasma interaction; and completing design of subsystems: electronejecting plasma contactor, power module, interface elements, deployment mechanism, and tether-tape/end-mass. This will be followed by subsystems manufacturing and by currentcollection, free-fall, and hypervelocity impact tests.

“CAMINHOS PARA DEUS” PROPOSTAS RELIGIOSAS DIVERGENTES E IDENTIDADE DO GRUPO JOANINO: UMA LEITURA EM JOÃO 13.33-14.31

No Quarto Evangelho Jesus se apresenta por meio de metáforas, sendo o objeto de nossa pesquisa a frase: “Eu sou o caminho, e a verdade, e a vida”, que será o ponto de partida condutor em busca da identidade do grupo joanino. No final do primeiro século, o grupo joanino se entende como fiéis herdeiros de Jesus, agora seguidores do discípulo João (filho de Zebedeu), o qual caminhou com Jesus. O grupo não se apresenta alheio à realidade da multiplicidade religiosa do período, mas está atento aos conflitos e aos caminhos divergentes para Deus. Isso nos aponta o quão identitário é o tema. A partir de uma leitura em João 13.33-14.31, nossa dissertação tem como objeto o modo como o grupo joanino recebe essa mensagem no imaginário, a exterioriza e reage no cotidiano, bem como os grupos posteriores do gnosticismo —como o Evangelho da Verdade da Biblioteca Copta de Nag Hammadi, elaborado a partir de leituras ulteriores que plasmam o mundo simbólico imaginário, cultivando diferentes características de pertença, gerando a identidade do grupo joanino.

Characterization of inhibitory and stimulatory forms of the murine natural killer cell receptor 2B4

The receptor 2B4 belongs to the Ig superfamily and is found on the surface of all murine natural killer (NK) cells as well as T cells displaying non-MHC-restricted cytotoxicity. Previous studies have suggested that 2B4 is an activating molecule because cross-linking of this receptor results in increased cytotoxicity and γ-interferon secretion as well as granule exocytosis. However, it was recently shown that the gene for 2B4 encodes two different products that arise by alternative splicing. These gene products differ solely in their cytoplasmic domains. One form has a cytoplasmic tail of 150 amino acids (2B4L) and the other has a tail of 93 amino acids (2B4S). To determine the function of each receptor, cDNAs for 2B4S and 2B4L were transfected into the rat NK cell line RNK-16. Interestingly, the two forms of 2B4 had opposing functions. 2B4S was able to mediate redirected lysis of P815 tumor targets, suggesting that this form represents an activating receptor. However, 2B4L expression led to an inhibition of redirected lysis of P815 targets when the mAb 3.2.3 (specific for rat NKRP1) was used. In addition, 2B4L constitutively inhibits lysis of YAC-1 tumor targets. 2B4L is a tyrosine phosphoprotein, and removal of domains containing these residues abrogates its inhibitory function. Like other inhibitory receptors, 2B4L associates with the tyrosine phosphatase SHP-2. Thus, 2B4L is an inhibitory receptor belonging to the Ig superfamily.

Estrogen receptor (ER) modulators each induce distinct conformational changes in ER α and ER β

Estrogen receptor (ER) modulators produce distinct tissue-specific biological effects, but within the confines of the established models of ER action it is difficult to understand why. Previous studies have suggested that there might be a relationship between ER structure and activity. Different ER modulators may induce conformational changes in the receptor that result in a specific biological activity. To investigate the possibility of modulator-specific conformational changes, we have applied affinity selection of peptides to identify binding surfaces that are exposed on the apo-ERs α and β and on each receptor complexed with estradiol or 4-OH tamoxifen. These peptides are sensitive probes of receptor conformation. We show here that ER ligands, known to produce distinct biological effects, induce distinct conformational changes in the receptors, providing a strong correlation between ER conformation and biological activity. Furthermore, the ability of some of the peptides to discriminate between different ER α and ER β ligand complexes suggests that the biological effects of ER agonists and antagonists acting through these receptors are likely to be different.

Direct adenovirus-mediated gene transfer of interleukin 1 and tumor necrosis factor α soluble receptors to rabbit knees with experimental arthritis has local and distal anti-arthritic effects

Adenoviral vectors were used to deliver genes encoding a soluble interleukin 1 (IL-1)-type I receptor-IgG fusion protein and/or a soluble type I tumor necrosis factor α (TNFα) receptor-IgG fusion protein directly to the knees of rabbits with antigen-induced arthritis. When tested individually, knees receiving the soluble IL-1 receptor had significantly reduced cartilage matrix degradation and white blood cell infiltration into the joint space. Delivery of the soluble TNFα receptor was less effective, having only a moderate effect on white blood cell infiltration and no effect on cartilage breakdown. When both soluble receptors were used together, there was a greater inhibition of white blood cell infiltration and cartilage breakdown with a considerable reduction of synovitis. Interestingly, anti-arthritic effects were also seen in contralateral control knees receiving only a marker gene, suggesting that sustained local inhibition of disease activity in one joint may confer an anti-arthritic effect on other joints. These results suggest that local intra-articular gene transfer could be used to treat systemic polyarticular arthritides.

Computerized polymorphic marker identification: Experimental validation and a predicted human polymorphism catalog

A computational system for the prediction of polymorphic loci directly and efficiently from human genomic sequence was developed and verified. A suite of programs, collectively called pompous (polymorphic marker prediction of ubiquitous simple sequences) detects tandem repeats ranging from dinucleotides up to 250 mers, scores them according to predicted level of polymorphism, and designs appropriate flanking primers for PCR amplification. This approach was validated on an approximately 750-kilobase region of human chromosome 3p21.3, involved in lung and breast carcinoma homozygous deletions. Target DNA from 36 paired B lymphoblastoid and lung cancer lines was amplified and allelotyped for 33 loci predicted by pompous to be variable in repeat size. We found that among those 36 predominately Caucasian individuals 22 of the 33 (67%) predicted loci were polymorphic with an average heterozygosity of 0.42. Allele loss in this region was found in 27/36 (75%) of the tumor lines using these markers. pompous provides the genetic researcher with an additional tool for the rapid and efficient identification of polymorphic markers, and through a World Wide Web site, investigators can use pompous to identify polymorphic markers for their research. A catalog of 13,261 potential polymorphic markers and associated primer sets has been created from the analysis of 141,779,504 base pairs of human genomic sequence in GenBank. This data is available on our Web site (pompous.swmed.edu) and will be updated periodically as GenBank is expanded and algorithm accuracy is improved.

Primary structure and tissue distribution of two novel proline-rich γ-carboxyglutamic acid���proteins

Two human cDNAs that encode novel vitamin K-dependent proteins have been cloned and sequenced. The predicted amino acid sequences suggest that both are single-pass transmembrane proteins with amino-terminal γ-carboxyglutamic acid-containing domains preceded by the typical propeptide sequences required for posttranslational γ-carboxylation of glutamic acid residues. The polypeptides, with deduced molecular masses of 23 and 17 kDa, are proline-rich within their putative cytoplasmic domains and contain several copies of the sequences PPXY and PXXP, motifs found in a variety of signaling and cytoskeletal proteins. Accordingly, these two proteins have been called proline-rich Gla proteins (PRGP1 and PRGP2). Unlike the γ-carboxyglutamic acid domain-containing proteins of the blood coagulation cascade, the two PRGPs are expressed in a variety of extrahepatic tissues, with PRGP1 and PRGP2 most abundantly expressed in the spinal cord and thyroid, respectively, among those tissues tested. Thus, these observations suggest a novel physiological role for these two new members of the vitamin K-dependent family of proteins.

Modulation of cognition-specific cortical activity by gonadal steroids: A positron-emission tomography study in women

There is considerable evidence from animal studies that gonadal steroid hormones modulate neuronal activity and affect behavior. To study this in humans directly, we used H215O positron-emission tomography to measure regional cerebral blood flow (rCBF) in young women during three pharmacologically controlled hormonal conditions spanning 4–5 months: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate (Lupron), Lupron plus estradiol replacement, and Lupron plus progesterone replacement. Estradiol and progesterone were administered in a double-blind cross-over design. On each occasion positron-emission tomography scans were performed during (i) the Wisconsin Card Sorting Test, a neuropsychological test that physiologically activates prefrontal cortex (PFC) and an associated cortical network including inferior parietal lobule and posterior inferolateral temporal gyrus, and (ii) a no-delay matching-to-sample sensorimotor control task. During treatment with Lupron alone (i.e., with virtual absence of gonadal steroid hormones), there was marked attenuation of the typical Wisconsin Card Sorting Test activation pattern even though task performance did not change. Most strikingly, there was no rCBF increase in PFC. When either progesterone or estrogen was added to the Lupron regimen, there was normalization of the rCBF activation pattern with augmentation of the parietal and temporal foci and return of the dorsolateral PFC activation. These data directly demonstrate that the hormonal milieu modulates cognition-related neural activity in humans.

Maternal death and obstetric care audits in Nigeria : a systematic review of barriers and enabling factors in the provision of emergency care

Acknowledgements We would like to thank Yutaka Osakabe for co-ordinating the retrieval of full text articles. The John D. and Catherine T. MacArthur Foundation supported this study, grant number 12-100074-000-INP

Digital Innovation Through Partnership Between Nature Conservation Organisations and Academia : A Qualitative Impact Assessment

We would like to thank all interviewees for sharing their experiences of working with academics, and the guest editor and three anonymous reviewers for valuable comments on earlier versions of the work. The research in this paper is supported by the RCUK dot.rural Digital economy Research Hub, University of Aberdeen (Grant reference: EP/G066051/1).

Digital Innovation Through Partnership Between Nature Conservation Organisations and Academia : A Qualitative Impact Assessment

We would like to thank all interviewees for sharing their experiences of working with academics, and the guest editor and three anonymous reviewers for valuable comments on earlier versions of the work. The research in this paper is supported by the RCUK dot.rural Digital economy Research Hub, University of Aberdeen (Grant reference: EP/G066051/1).

p53-dependent regulation of MDR1 gene expression causes selective resistance to chemotherapeutic agents

Loss of functional p53 paradoxically results in either increased or decreased resistance to chemotherapeutic drugs. The inconsistent relationship between p53 status and drug sensitivity may reflect p53’s selective regulation of genes important to cytotoxic response of chemotherapeutic agents. We reasoned that the discrepant effects of p53 on chemotherapeutic cytotoxicity is due to p53-dependent regulation of the multidrug resistance gene (MDR1) expression in tumors that normally express MDR1. To test the hypothesis that wild-type p53 regulates the endogenous mdr1 gene we stably introduced a trans-dominant negative (TDN) p53 into rodent H35 hepatoma cells that express P-glycoprotein (Pgp) and have wild-type p53. Levels of Pgp and mdr1a mRNA were markedly elevated in cells expressing TDN p53 and were linked to impaired p53 function (both transactivation and transrepression) in these cells. Enhanced mdr1a gene expression in the TDN p53 cells was not secondary to mdr1 gene amplification and Pgp was functional as demonstrated by the decreased uptake of vinblastine. Cytotoxicity assays revealed that the TDN p53 cell lines were selectively insensitive to Pgp substrates. Sensitivity was restored by the Pgp inhibitor reserpine, demonstrating that only drug retention was the basis for loss of drug sensitivity. Similar findings were evident in human LS180 colon carcinoma cells engineered to overexpress TDN p53. Therefore, the p53 inactivation seen in cancers likely leads to selective resistance to chemotherapeutic agents because of up-regulation of MDR1 expression.