34 research outputs found
Stereochemistry of the methyl group in (R)-3-methylitaconate derived by rearrangement of 2-methylideneglutarate catalysed by a coenzyme B-12-dependent mutase
2-Methylidenegtutarate mutase is an adenosylcobalamin (coenzyme B-12)-dependent enzyme that catalyses the equilibration of 2-methylideneglutarate with (R)-3-methylitaconate. This reaction is believed to occur via protein-bound free radicals derived from substrate and product. The stereochemistry of the formation Of the methyl group of 3-mechylitaconate has been probed using a 'chiral methyl group'. The methyl group in 3-([H-2(1),H-3]methyl)itaconate derived from either (R)- or (S)-2-methylidene[3-H-2(1),3-H-3(1)]glutarate was a 50:50 mixture of (R)- and (S)-forms. It is concluded that the barrier to rotation about the C-C bond between the methylene radical centre and adjacent C-atom in the product-related radical [(CH)-C-.,CH(-O2CC=CH2)CO2-] is relatively low, and that the interaction of the radical with cob(II)alamin is minimal. Hence, cob(II)alamin is a spectator of the molecular rearrangement of the substrate radical to product radical
Predicting Microenvironment in CXCR4- and FAP-Positive Solid Tumors—A Pan-Cancer Machine Learning Workflow for Theranostic Target Structures
(1) Background: C-X-C Motif Chemokine Receptor 4 (CXCR4) and Fibroblast Activation Protein Alpha (FAP) are promising theranostic targets. However, it is unclear whether CXCR4 and FAP positivity mark distinct microenvironments, especially in solid tumors. (2) Methods: Using Random Forest (RF) analysis, we searched for entity-independent mRNA and microRNA signatures related to CXCR4 and FAP overexpression in our pan-cancer cohort from The Cancer Genome Atlas (TCGA) database—representing n = 9242 specimens from 29 tumor entities. CXCR4- and FAP-positive samples were assessed via StringDB cluster analysis, EnrichR, Metascape, and Gene Set Enrichment Analysis (GSEA). Findings were validated via correlation analyses in n = 1541 tumor samples. TIMER2.0 analyzed the association of CXCR4 / FAP expression and infiltration levels of immune-related cells. (3) Results: We identified entity-independent CXCR4 and FAP gene signatures representative for the majority of solid cancers. While CXCR4 positivity marked an immune-related microenvironment, FAP overexpression highlighted an angiogenesis-associated niche. TIMER2.0 analysis confirmed characteristic infiltration levels of CD8+ cells for CXCR4-positive tumors and endothelial cells for FAP-positive tumors. (4) Conclusions: CXCR4- and FAP-directed PET imaging could provide a non-invasive decision aid for entity-agnostic treatment of microenvironment in solid malignancies. Moreover, this machine learning workflow can easily be transferred towards other theranostic targets
Photohormones Enable Optical Control of the Peroxisome Proliferator-Activated Receptor g (PPARg)
S.10908-10920Photopharmacology aims at the optical control of protein activity using synthetic photoswitches. This approach has been recently expanded to nuclear hormone receptors with the introduction of ""photohormones"" for the retinoic acid receptor, farnesoid X receptor, and estrogen receptor. Herein, we report the development and profiling of photoswitchable agonists for peroxisome proliferator-activated receptor g (PPARg). Based on known PPARg ligands (MDG548, GW1929, and rosiglitazone), we have designed and synthesized azobenzene derivatives, termed AzoGW1929 and AzoRosi, which were confirmed to be active in cell-based assays. Subsequent computer-aided optimization of AzoRosi resulted in the photohormone AzoRosi-4, which bound and activated PPARg preferentially in its light-activated cis-configuration.63Nr.1
OPERATIONAL ASPECTS OF ORBIT DETERMINATION WITH GPS FOR SMALL SATELLITES WITH A SAR PAYLOAD.
Scientific small satellite missions for remote sensing with Synthetic Aperture Radar (SAR) payloads or high accuracy optical sensors, pose very strict requirements on the accuracy of the reconstructed satellite positions, velocities and accelerations. Today usual GPS receivers can fulfill the accuracy requirements of this missions in most cases, but for low-cost-missions the decision for a appropriate satellite hardware has to take into account not only the reachable quality of data but also the costs. In this paper an analysis is carried out in order to assess which on board and ground equipment, which type of GPS data and processing methods are most appropriate to minimize mission costs and full satisfying mission payload requirements focusing the attention on a SAR payload
Reconstrução da mama: seis anos de experiência do núcleo de cirurgia plástica do Hopital Universitário Prof. Polydoro Ernani de São Thiago - UFSC
Trabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Dapartamento de Clínica Cirúrgica
Precise Orbit Determination for the TerraSAR-X Mission
The TerraSAR-X synthetic aperture radar mission relies exclusively on GPS tracking for a precise post-facto orbit reconstruction. Besides a redundant
MosaicGNSS single-frequency receiver, the satellite carries the Integrated GPS Occultation Receiver (IGOR), which provides low noise code- and carrier phase measurements on both the L1 and L2 frequencies. As part of the TerraSAR-X ground segment an automated precise orbit determination system has been built up at the German Space Operations Center (DLR/GSOC). The employed reduced-dynamic batch least-squares filter is designed to work with both ionosphere-free L1/L2 carrier phase data and the ionosphere-free L1 code/carrier combination. Depending on the available GPS receiver and measurement types, a 3D rms position accuracy between 1 m (MosaicGNSS single-frequency data) and 5-10 cm (IGOR dual-frequency data) has been demonstrated in pre-mission tests. Following a description of the TerraSAR-X mission and spacecraft, the paper describes the adopted orbit determination algorithms and processing methodology. The theoretical background is complemented with practical results from the CHAMP and GRACE missions as well as GPS signal simulator tests
Stereochemistry of the methyl group in (R)-3-methylitaconate derived by rearrangement of 2-methylideneglutarate catalysed by a coenzyme B12-dependent mutase
2-Methylideneglutarate mutase is an adenosylcobalamin (coenzyme B12)-dependent enzyme that catalyses the equilibration of 2-methylideneglutarate with (R)-3-methylitaconate. This reaction is believed to occur via protein-bound free radicals derived from substrate and product. The stereochemistry of the formation of the methyl group of 3-methylitaconate has been probed using a \u27chiral methyl group\u27. The methyl group in 3-([2H1,3H]methyl)itaconate derived from either (R)- or (S)-2-methylidene[3-2H1,3-3H1]glutarate was a 50 : 50 mixture of (R)- and (S)-forms. It is concluded that the barrier to rotation about the C-C bond between the methylene radical centre and adjacent C-atom in the product-related radical [CH2CH(-O2CC=CH2)CO2-] is relatively low, and that the interaction of the radical with cob(1I)alamin is minimal. Hence, cob(I1)alamin is a spectator of the molecular rearrangement of the substrate radical to product radical
Avaliação do grau de satisfação das pacientes submeditas à reconstrução do complexo aréolo-papilar no Hospital Universitário Polydoro Ernani de São Thiago.
Trabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Dapartamento de Clínica Cirúrgica
High cut-off microdialysis catheters to clinically investigate cytokine changes following flap transfer
Background:
‘Choke vessels’ are thought to dilate in the first 72 h when blood flow to an area is disrupted. This study used ‘high cut-off’ microdialysis catheters in clinical research to investigate factors mediating circulatory change within free flaps.
Methods:
Six patients undergoing DIEP flap breast reconstruction each had three ‘high cut-off’ microdialysis catheters, with a membrane modification allowing molecules as large as 100 kDa to pass, inserted into Hartrampf zones 1, 2 and 4 to assess multiple vascular territories. Microdialysis continued for 72 h post-operatively. Samples were analysed for interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα) and fibroblast growth factor basic (FGFβ).
Results:
Three hundred and twenty-four samples were analysed for IL-6, FGFβ and TNFα totalling 915 analyses. IL-6 showed an increasing trend until 36 h post-operatively before remaining relatively constant. Overall, there was an increase (p < 0.001) over the time period from 4 to 72 h, fitting a linear trend. TNFα had a peak around 20–24 h before a gradual decrease. There was a significant linear time trend (p = 0.029) between 4 and 76 h, decreasing over the time period. FGFβ concentrations did not appear to have any overall difference in concentration with time. The concentration however appeared to oscillate about a horizontal trend line. There were no differences between the DIEP zones in concentrations of cytokines collected.
Conclusion:
This study uses high-cut off microdialysis catheters to evaluate changes in cytokines, and requires further research to be undertaken to add to our knowledge of choke vessels and flap physiology
