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- Jordan, Ulf, 1974, et al.
(författare)
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On the effective diffusion length for microwave breakdown
- 2004
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Ingår i: Proc. 5th International Workshop on Multipactor, Corona and Passive Intermodulation, September 12 – 14, 2005, ESTEC, Noordwijk, The Netherlands In: Space RF Hardware (MULCOPIM' 2005). ; , s. 243-249
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Konferensbidrag (refereegranskat)
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| 2. |
- Beggs, J, et al.
(författare)
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Synaptology of trigemino- and spinothalamic lamina I terminations in the posterior ventral medial nucleus of the macaque
- 2003
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Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 459:4, s. 334-354
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Tidskriftsartikel (refereegranskat)abstract
- We used the electron microscope to examine lamina I trigemino- and spinothalamic (TSTT) terminations in the posterior part of the ventral medial nucleus (VMpo) of the macaque thalamus. Lamina I terminations were identified by anterograde labeling with biotinylated dextran, and 109 boutons on 38 terminal fibers were closely studied in series of ultrathin sections. Five unlabeled terminal boutons of similar appearance were also examined in detail. Three-dimensional, volume-rendered computer models were reconstructed from complete series of serial sections for 29 boutons on 10 labeled terminal fibers and one unlabeled terminal fiber. In addition, postembedding immunogold staining for GABA was obtained in alternate sections through 23 boutons. Lamina I TSTT terminations in VMpo generally have several large boutons (mean length = 2.16 ╡m, mean width = 1.29 ╡m) that are densely packed with vesicles and make asymmetric synaptic contacts on low-order dendrites of VMpo neurons (mean diameter 1.45 ╡m). They are closely associated with GABAergic presynaptic dendrites (PSDs), and nearly all form classic triadic arrangements (28 of 29 reconstructed boutons). Consecutive boutons on individual terminal fibers make multiple contacts with a single postsynaptic dendrite and can show evidence of progressive complexity. Dendritic appendages that enwrap and invaginate the terminal bouton constitute additional anatomic evidence for secure, high-fidelity synaptic transfer. These observations provide direct ultrastructural evidence supporting the hypothesis that VMpo is a lamina I TSTT thalamocortical relay nucleus in primates that subserves pain, temperature, itch, and other sensations related to the physiological condition of the body.
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| 3. |
- Lehmann, Ordan J, et al.
(författare)
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Fox's in development and disease.
- 2003
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Ingår i: Trends in genetics : TIG. - 0168-9525. ; 19:6, s. 339-44
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Forskningsöversikt (refereegranskat)abstract
- Since the first forkhead (Fox) gene was identified, the importance of this family of transcription factors has increased steadily with the discoveries of the diverse range of developmental processes that they regulate in eukaryotes. Among other processes, the Fox factors are important in the establishment of the body axis and the development of tissues from all three germ layers. In this article, we present some of the recent data on this gene family with reference to selected phenotypes observed in patients and model organisms, and the sensitivity of developmental processes to alterations in forkhead gene dosage.
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| 4. |
- Lehmann, O. J., et al.
(författare)
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Novel anterior segment phenotypes resulting from forkhead gene alterations: Evidence for cross-species conservation of function
- 2003
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 44:6, s. 2627-2633
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Mutations in murine and human Versions of an ancestrally related gene usually result in similar phenotypes. However, interspecics differences exist, and in the case of two forkhead transcription factor genes (FOXC1 and FOXC2), these differences include corneal or anterior segment phenotypes, respectively. This study was undertaken to determine whether such discrepancies provide an opportunity for identifying novel human-murine ocular phenotypes. METHODS. Four pedigrees with early-onset glaucoma phenotypes secondary to segmental chromosomal duplications or deletions encompassing FOXC1 and 18 individuals from 9 FOXC2 mutation pedigrees underwent detailed ocular phenotyping. Subsequently, mice with mutations in Foxc1 or a related forkhead gene, Foxe3, were assessed for features of the human phenotypes. RESULTS. A significant increase in central corneal thickness was present in affected individuals from the segmental duplication pedigrees compared with their unaffected relatives (mean increase 13%, maximum 35%, P < 0.05). Alterations in corneal thickness were present in mice heterozygous and homozygous for Foxe3 mutations but neither in Foxc1 heterozygotes nor the small human segmental deletion pedigree. Mutations in FOXC2 resulted in ocular anterior segment anomalies. These were more severe and prevalent with mutations involving the forkhead domain. CONCLUSIONS. Normal corneal development is dependent on the precise dose and levels of activity of certain forkhead transcription factors. The altered corneal thickness attributable to increased forkhead gene dosage is particularly important, because it may affect the clinical management of certain glaucoma subtypes and lead to excessive treatment. The FOXC1 and Foxe3 data, taken together with the novel ocular phenotypes of FOXC2 mutations, highlight the remarkable cross-species conservation of function among forkhead genes.
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| 6. |
- Shuman, Cynthia F, 1972-
(författare)
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Interaction Characteristics of Viral Protease Targets and Inhibitors : Perspectives for drug discovery and development of model systems
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Viral proteases are important targets for anti-viral drugs. Discovery of protease inhibitors as anti-viral drugs is aided by an understanding of the interactions between viral protease and inhibitors. This thesis addresses the characterization of protease-inhibitor interactions for application to drug discovery and model system development.The choice of a relevant target is essential to molecular interaction studies. Therefore, full-length NS3 protein of hepatitis C virus (HCV) was obtained, providing a more relevant target and a better model for the development of HCV protease inhibitors. In addition, resistance to anti-viral drugs, a serious problem in the treatment of AIDS, prompted the investigation of resistant variants of human immunodeficiency virus (HIV) protease.Drug resistance was initially explored by characterization of the interactions between a series of closely related inhibitors and resistant variants of HIV protease, using an inhibition assay to determine the inhibition dissociation constants (Ki). The relationship between structure, activity and resistance profiles was not clarified, indicating that the effect of structural changes in the inhibitors and the protease are not predictable and must be analyzed case wise. It was proposed that additional kinetic characterization of the interactions was required and a biosensor-based method allowing for determination of affinity, KD, and interaction rate constants, kon and koff, was adopted. The increased physiological relevance of this method was confirmed, and the affinity data have better correlation with cell culture data. In addition, interactions between clinical inhibitors of HIV protease and enzyme variants indicate that increased dissociation rates (koff) are associated with the development of resistance.Thermodynamic characterization of the interactions between HIV-1 protease and clinically relevant inhibitors revealed distinct energetic characteristics for inhibitors. The resolution of the energetics of association and dissociation identified an inhibitor with unique interaction characteristics and confirmed the validity of using this method for further characterization of molecular interactions.This work resulted in the development of model systems for the analysis of kinetics, resistance and thermodynamic characteristics of protein-inhibitor interactions. The results give increased understanding of the biomolecular interactions and can be applied to drug discovery.
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| 7. |
- Zlatev, Jordan, et al.
(författare)
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Idiomatic entrenchment and semantic priming
- 2004
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Ingår i: Linguagem, Cultura e Cognição. - Coimbra : Almedina. - 9724022641 - 9724023036 ; , s. 309-334
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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