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| 2. |
- Littleton, JM, et al.
(författare)
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Challenges to medications development in treating alcohol dependence: An international perspective - Summary of a symposium held at the ESBRA Congress, Prague, 13 September 2003
- 2004
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Ingår i: Alcohol and Alcoholism. - : Oxford University Press (OUP). - 1464-3502. ; 39:4, s. 271-275
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Tidskriftsartikel (refereegranskat)abstract
- Few medications for treating alcohol dependence exist. Greater partnership is needed between academia and the pharmaceutical industry to develop, licence and market efficacious medications for treating alcohol dependence. Methodologies that span the divide between preclinical and large-scale clinical studies need to be developed in order to provide sufficient information on safety, toleration, drug-interaction profile and efficacy, with which to guide development decisions. Due to the heterogeneous nature of alcohol dependence, the effort of developing an efficacious medication is likely to be enhanced by clearer choices about the characteristics of the population. Careful consideration of potential mechanism of action of the putative therapeutic medication should enable the appropriate choice of drinking endpoint. The pharmaceutical industry in collaboration with academia might need to develop new approaches to determining appropriate treatment endpoints with regulatory bodies. The investment risk to industry should be appraised not only in terms of the rather poor results of previous marketing efforts but with a view to the opportunity to penetrate a potentially enormous and largely untapped market.
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| 3. |
- Alderman, Byron, et al.
(författare)
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A New Pillar Geometry for Heterostructure Barrier Varactor Diodes
- 2001
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Ingår i: 12th International Symposium on Space Terahertz Technology. ; , s. 330-339
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Konferensbidrag (refereegranskat)abstract
- We report on a novel diode geometry, with reduced thermal resistance, for Heterostructure Barrier Varactor, HBV, diodes. The pillar geometry presented here involves the complete removal of the substrate, electrical contacted is made by the forward and reverse side processing of metallic pillars. We propose that there is a limit to the maximum number of barriers that can be used to increase the power capability of a HBV. An analytical model has been developed to study these effects. In considering the case of a perfect thermal heat sink the limit is found to be fourteen, in applying this model to the new pillar structure this is reduced to six.
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| 7. |
- Ibarrola, Nieves, et al.
(författare)
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Cloning of a novel signaling molecule, AMSH-2, that potentiates transforming growth factor beta signaling.
- 2004
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Ingår i: BMC Cell Biology. - 1471-2121. ; 5:1, s. 2-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transforming growth factor-betas (TGF-betas), bone morphogenetic proteins (BMPs) and activins are important regulators of developmental cell growth and differentiation. Signaling by these factors is mediated chiefly by the Smad family of latent transcription factors. RESULTS: There are a large number of uncharacterized cDNA clones that code for novel proteins with homology to known signaling molecules. We have identified a novel molecule from the HUGE database that is related to a previously known molecule, AMSH (associated molecule with the SH3 domain of STAM), an adapter shown to be involved in BMP signaling. Both of these molecules contain a coiled-coil domain located within the amino-terminus region and a JAB (Domain in Jun kinase activation domain binding protein and proteasomal subunits) domain at the carboxy-terminus. We show that this novel molecule, which we have designated AMSH-2, is widely expressed and its overexpression potentiates activation of TGF-beta-dependent promoters. Coimmunoprecipitation studies indicated that Smad7 and Smad2, but not Smad3 or 4, interact with AMSH-2. We show that overexpression of AMSH-2 decreases the inhibitory effect of Smad7 on TGF-beta signaling. Finally, we demonstrate that knocking down AMSH-2 expression by RNA interference decreases the activation of 3TP-lux reporter in response to TGF-beta. CONCLUSIONS: This report implicates AMSH and AMSH-2 as a novel family of molecules that positively regulate the TGF-beta signaling pathway. Our results suggest that this effect could be partially explained by AMSH-2 mediated decrease of the action of Smad7 on TGF-beta signaling pathway.
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| 8. |
- Krüger, H., et al.
(författare)
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Four years of Ulysses dust data: 1996-1999
- 2001
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Ingår i: Planetary and Space Science. - 1873-5088. ; 49:13, s. 1303-1324
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Tidskriftsartikel (refereegranskat)abstract
- The Ulysses spacecraft is orbiting the Sun on a highly inclined ellipse(/i=79°, perihelion distance 1.3 AU, aphelion distance 5.4 AU).Between January /1996 and December /1999 the spacecraft was beyond 3 AUfrom the Sun and crossed the ecliptic plane at aphelion in May /1998. Inthis 4-yr period 218 dust impacts were recorded with the dust detectoron board. We publish and analyse the complete data set of both raw andreduced data for particles with masses10-16-10-8g. Together with 1477 dust impactsrecorded between launch of Ulysses and the end of /1995 publishedearlier (Grün et al., Planet. Space Sci. 43 (/1995a) 971;Krüger et al., Planet. Space Sci. 47 (/1999b) 363), a data set of1695 dust impacts detected with the Ulysses sensor between October /1990and December /1999 is now available. The impact rate measured between1996 and 1999 was relatively constant with about 0.2 impacts per day.The impact direction of the majority of the impacts is compatible withparticles of interstellar origin, the rest are most likelyinterplanetary particles. The observed impact rate is compared with amodel for the flux of interstellar dust particles. The flux of particlesseveral micrometres in size is compared with the measurements of thedust instruments on board Pioneer 10 and Pioneer 11 beyond 3 AU (Humes,J. Geophys. Res. 85 /(1980) 5841). Between 3 and 5 AU, Pioneer resultspredict that Ulysses should have seen 5 times more (~10mum sized)particles than actually detected.
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| 9. |
- Krüger, H., et al.
(författare)
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One year of Galileo dust data from the Jovian system: 1996
- 2001
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Ingår i: Planetary and Space Science. - 1873-5088. ; 49:13, s. 1285-1301
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Tidskriftsartikel (refereegranskat)abstract
- The dust detector system onboard Galileo has recoding dust impacts incircumjovian space since the spacecraft was injected into a bound orbitabout Jupiter in December 1995. This is the sixth in a series of papersdedicated to presenting Galileo and Ulysses dust data. We present datafrom the Galileo dust instrument for the period January to December 1996when the spacecraft completed four orbits about Jupiter (G1, G2, C3 andE4). Data were obtained as high-resolution realtime science data orrecorded data during a time period of 100 days, or via memory read-outsduring the remaining times. Because the data transmission rate of thespacecraft is very low, the complete data set (i.e. all parametersmeasured by the instrument during impact of a dust particle) for only 2%(5353) of all particles detected could be transmitted to Earth; theother particles were only counted. Together with the data for 2883particles detected during Galileo's interplanetary cruise and publishedearlier, complete data of 8236 particles detected by the Galileo dustinstrument from 1989 to 1996 are now available. The majority ofparticles detected are tiny grains (about 10nm in radius) originatingfrom Jupiter's innermost Galilean moon Io. These grains have beendetected throughout the Jovian system and the highest impact ratesexceeded 100min-1. A small number of grains has been detectedin the close vicinity of the Galilean moons Europa, Ganymede andCallisto which belong to impact-generated dust clouds formed by (mostlysubmicrometer sized) ejecta from the surfaces of the moons (Krügeret al., /1999e. Nature 399, 558). Impacts of submicrometer to micrometersized grains have been detected throughout the Jovian system andespecially in the region between the Galilean moons.
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| 10. |
- Mann, D. L., et al.
(författare)
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Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)
- 2004
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Ingår i: Circulation. - 1524-4539. ; 109:13, s. 1594-602
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies in experimental models and preliminary clinical experience suggested a possible therapeutic role for the soluble tumor necrosis factor antagonist etanercept in heart failure. METHODS AND RESULTS: Patients with New York Heart Association class II to IV chronic heart failure and a left ventricular ejection fraction < or =0.30 were enrolled in 2 clinical trials that differed only in the doses of etanercept used. In RECOVER, patients received placebo (n=373) or subcutaneous etanercept in doses of 25 mg every week (n=375) or 25 mg twice per week (n=375). In RENAISSANCE, patients received placebo (n=309), etanercept 25 mg twice per week (n=308), or etanercept 25 mg 3 times per week (n=308). The primary end point of each individual trial was clinical status at 24 weeks. Analysis of the effect of the 2 higher doses of etanercept on the combined outcome of death or hospitalization due to chronic heart failure from the 2 studies was also planned (RENEWAL). On the basis of prespecified stopping rules, both trials were terminated prematurely owing to lack of benefit. Etanercept had no effect on clinical status in RENAISSANCE (P=0.17) or RECOVER (P=0.34) and had no effect on the death or chronic heart failure hospitalization end point in RENEWAL (etanercept to placebo relative risk=1.1, 95% CI 0.91 to 1.33, P=0.33). CONCLUSIONS: The results of RENEWAL rule out a clinically relevant benefit of etanercept on the rate of death or hospitalization due to chronic heart failure.
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