DOSCH DESIGN - 3D: Transport 2010
Roan Distilo
Dosch 3D: Passenger Transportation offers an impressive array of 24 highly-detailed 3D models that cater to every passenger transportation need, whether it's a small 2-wheel trailer or a top-of-the-line luxury RV, a commuter train or a high-speed train, or even a sleek and futuristic monorail system.
Since Dosch Design does not (cannot) know how the buyer will use/change the 3D models/objects of trademarked products, we advise the buyer/user of the models/objects to contact the manufacturer prior (!) to the publication of the new 3D-designs, and verify that the -intended- final design product is in compliance with the legal use of the protected image/trademark.
The product contains 32 detailed 3D-models of transportation vehicles. Included are a.o. buses, trucks, construction machinery, small ships/boats, a train.
Use them in technical illustrations and architectural visualizations.
Since Dosch Design does not (cannot) know how the buyer will use/change the 3D models/objects of trademarked products we advise the buyer/user of D3D: Transport models/objects to contact the manufacturer of the transport vehicle
"Visualisation is our passion! For over 20 years, the name Dosch Design has stood for the highest level of quality in the development of computer graphics products in the fields of 3D design and visualisation.
ACMH has designed and built a state-of-the-art, two track Emergency Department. The Acute Care track has larger, private treatment rooms with privacy curtains, sliding glass doors and adequate space for all necessary equipment. The Express Care track more efficiently serves those patients who have less acute illnesses. With an expected time-to-treatment in the range of 20 minutes, Express Care patients have an overall length-of-stay significantly below the national average.
Since May 2007, STAT MedEvac, a medical transport helicopter, has been permanently based at ACMH Hospital. The base is staffed with an EMS Pilot, a Flight Nurse, and a Flight Paramedic 24 hours per day, 365 day per year. This allows ACMH Hospital and STAT MedEvac to provide an additional benefit toward addressing the overall healthcare needs of the community, while intimately linking our hospital to other major Pittsburgh hospitals.
The features that STAT MedEvac has to offer are numerous. The STAT MedEvac helicopter is equipped with everything that is available in an ambulance, and more. The Flight Nurse who is present on every flight is permitted to administer prescribed medicines that paramedics in an ambulance cannot give. Additionally, the helicopter is stocked with medical supplies including, but not limited to, packed red blood cells, a ventilator, and oxygen equipment. It is also equipped with balloon pump capabilities, which can temporarily assist a failing heart. All of these provide continuing care to the patient during transport.
STAT MedEvac is the only critical care transport program in Pennsylvania to be fully accredited in all modes of transport (rotor wing, fixed wing, ground critical care and medical escort). The accrediting agency states that two of the highest priorities of an air medical or ground inter-facility transport service are: (1) patient care, and (2) safety of the transport environment. The STAT MedEvac team believes in these priorities as well, and puts them into practice on a daily basis.
During oogenesis, the egg prepares for fertilization and early embryogenesis. As a consequence, vesicle transport is very active during vitellogenesis, and oocytes are an outstanding system to study regulators of membrane trafficking. Here, we combine zebrafish genetics and the oocyte model to identify the molecular lesion underlying the zebrafish souffle (suf) mutation. We demonstrate that suf encodes the homolog of the Hereditary Spastic Paraplegia (HSP) gene SPASTIZIN (SPG15). We show that in zebrafish oocytes suf mutants accumulate Rab11b-positive vesicles, but trafficking of recycling endosomes is not affected. Instead, we detect Suf/Spastizin on cortical granules, which undergo regulated secretion. We demonstrate genetically that Suf is essential for granule maturation into secretion competent dense-core vesicles describing a novel role for Suf in vesicle maturation. Interestingly, in suf mutants immature, secretory precursors accumulate, because they fail to pinch-off Clathrin-coated buds. Moreover, pharmacological inhibition of the abscission regulator Dynamin leads to an accumulation of immature secretory granules and mimics the suf phenotype. Our results identify a novel regulator of secretory vesicle formation in the zebrafish oocyte. In addition, we describe an uncharacterized cellular mechanism for Suf/Spastizin activity during secretion, which raises the possibility of novel therapeutic avenues for HSP research.
Oocytes of egg laying animals frequently represent the biggest cell type of a species. The size of the egg is a consequence of active transport processes, e.g. the import of yolk proteins, which results in the massive storage of vesicles. In addition, secretory vesicles termed cortical granules are stored in the oocyte to be discharged right after fertilization during cortical reaction, which also occurs in mammals. Their secretion leads to chorion expansion, which prevents the lethal entry of additional sperm and protects the developing embryo against physical damage. Mutants with a defect in membrane transport are successful tools to discover genes regulating vesicle formation. We molecularly identify the disrupted gene in the recessive maternal-effect mutation souffle, which encodes a homolog of human SPASTIZIN. SPASTIZIN was previously implicated in endocytosis, but our cellular analysis of mutant oocytes connects this gene also with the regulation of cortical granule exocytosis. More precisely, we show that Suf/Spastizin is crucial for the maturation of cortical granules into secretion competent vesicles describing a novel role for this protein. Since SPASITIZN causes the disease Hereditary Spastic Paraplegia in humans, our results will help to decipher the pathogenesis of this neurodegenerative disorder.
Mutants provide an essential tool to determine the endogenous role of a gene. Previously, we used a mutagenesis screen in zebrafish to discover vertebrate regulators of egg development and early embryogenesis, which isolated the souffle (suf) mutation named after its defect during oogenesis [28]. Here, we positionally cloned suf and show that it encodes the homolog of SPASTIZIN. In suf mutants, we show that oocytes expand a Rab11b-positive compartment, but correctly transport the recycling cargo Transferrin. Moreover, Suf colocalizes with Rab11b on secretory vesicles called cortical granules in the oocyte. We demonstrate genetically that Suf/Spastizin is essential for the formation of cortical granules. Importantly, our subcellular analysis indicates that loss of Suf/Spastizin inhibits vesicle maturation, probably during sorting, which is necessary to complete the formation of Clathrin-coated buds and eventually to pinch-off vesicles. Finally, blocking vesicle scission with the pharmacological Dynamin-inhibitor Dynasore mimics the mutant phenotype supporting the hypothesis that Suf is required for vesicle fission, which is critical for the maturation of secretory granules in the egg. Collectively, these results identify Suf/Spastizin as a novel key gene controlling the maturation of cortical granules in zebrafish oocytes, which may also bring us closer to understand the cellular etiology of HSP.
In tissue culture cells, the FYVE domain of Suf/Spastizin interacts with the endosomal lipid PI3P indicating a role in endosomal trafficking [21]. Moreover, in human and mouse cells Spastizin binds to the novel AP5 complex regulating endosomal transport [22], [26], [27], [40]. To examine genetically in zebrafish oocytes, whether Suf/Spastizin is involved in endocytosis during oogenesis, we compared endosomal compartments between wt and mutant. The gross morphology of oocyte vesicles showed no difference in early endosomes (Rab5) or late endosomes (Rab7) (Figure 3A) [41], [42]. In contrast, Rab11b-positive recycling endosomes showed a remarkable transformation of their tubular shape in wt to patches accumulating below the nuclei of the surrounding follicle cells in mutant oocytes (Figure 3A) [43].
To functionally analyze during oogenesis whether the observed accumulation of the compartment-specific Rab proteins reflects a defect in the corresponding transport route as described for tissue culture cells, we established cargo trafficking assays in the zebrafish oocyte. LDL follows the degradative transport route to lysosomes and the yolk-receptor belongs to the LDL-receptor superfamily [44], [45]. Adding fluorescent LDL to the culture medium labeled yolk globules in zebrafish oocytes, which correspond to lysosomes of somatic cells [46]. However, we observed no difference in the LDL transport to wt or mutant lysosomes, which were also identified by a characteristic black halo after fixation (Figure 3D, also visible in Figure 3B) suggesting that transport along the degradative pathway is not disrupted.
A major question arising from our study is how the various observed phenotypes could be reconciled. Two alternative scenarios integrate all results: Suf/Spastizin primarily acts in MVB/lysosomes and the maturation defect of secretory vesicles is secondary e.g. through retrograde transport to the Trans-Golgi-Network [reviewed in 98] or alternatively, Suf/Spastizin primarily acts in immature secretory granules and the lysosomal defect is secondary e.g. through sorting of the mannose-6-phosphate receptors transporting hydrolytic enzymes into lysosomes [reviewed in 71], [99]. Currently, we favor the second model, which is supported by proteins such as AP-3, which play a role in dense core vesicle formation [100] and lysosomal maturation [reviewed in 101]. By contrast, defects in retrograde transport were hitherto not reported to affect the formation of the dense core in secretory granules as in the suf mutant, but rather lead to missorting of lysosomal enzymes [reviewed in 98]. This model would also predict that cargo sorted away in immature secretory granules is necessary for homotypic lysosome fusion (Figure 7H) as described in other cells [102]. These open questions make clear that additional studies are necessary to determine the precise role of Suf/Spastizin and whether a defect in lysosome formation or secretion can lead to neuronal degeneration in HSP patients.
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