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Engineering Studies (engineering + studies)

Distribution by Scientific Domains

Chemistry	50%

Selected Abstracts

Crystal structure of a staphylokinase variant

FEBS JOURNAL, Issue 2 2002
A model for reduced antigenicity
Staphylokinase (SAK) is a 15.5-kDa protein from Staphylococcus aureus that activates plasminogen by forming a 1 : 1 complex with plasmin. Recombinant SAK has been shown in clinical trials to induce fibrin-specific clot lysis in patients with acute myocardial infarction. However, SAK elicits high titers of neutralizing antibodies. Biochemical and protein engineering studies have demonstrated the feasibility of generating SAK variants with reduced antigenicity yet intact thrombolytic potency. Here, we present X-ray crystallographic evidence that the SAK(S41G) mutant may assume a dimeric structure. This dimer model, at 2.3-Å resolution, could explain a major antigenic epitope (residues A72,F76 and residues K135-K136) located in the vicinity of the dimer interface as identified by phage-display. These results suggest that SAK antigenicity may be reduced by eliminating dimer formation. We propose several potential mutation sites at the dimer interface that may further reduce the antigenicity of SAK. [source]

Streamflow estimation using optimal regional dependency function

HYDROLOGICAL PROCESSES, Issue 25 2009
Abdüsselam Altunkaynak
Abstract The determination of spatial dependency of regionalized variable (ReV) is important in engineering studies. Regional dependency function that leads to calculation of weighting coefficients is required in order to make regional or point-wise estimations. After obtaining this dependency function, it is possible to complete missing records in the time series and locate new measurement station. Also determination of regional dependency function is also useful to understand the regional variation of ReV. Point Cumulative Semi-Variogram (PCSV) is another methodology to understand the regional dependency of ReV related to the magnitude and the location. However, this methodology is not useful to determine the weighting coefficient, which is required to make regional and point-wise estimations. However, in Point Semi-Variogram (PSV) proposed here, weighting coefficient depends on both magnitude and location. Although the regional dependency function has a fluctuating structure in PSV approach, this function gradually increases with distance in PCSV. The study area is selected in Mississippi river basin with 38 streamflow stations used for PCSV application before. It is aimed to compare two different geostatistical models for the same data set. PSV method has an ability to determine the value of variable along with optimum number of neighbour stations and influence radius. PSV and slope PSV approaches are compared with the PCSV. It was shown that slope slope point semi-variogram (SPSV) approaches had relative error below 5%, and PSV and PCSV methods revealed relative errors below 10%. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Stemness, fusion and renewal of hematopoietic and embryonic stem cells

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2003
S. Constantinescu
Abstract Development of replacement cell therapies awaits the identification of factors that regulate nuclear reprogramming and the mechanisms that control stem cell renewal and differentiation. Once such factors and signals will begin to be elucidated, new technologies will have to be envisaged where uniform differentiation of adult or embryonic stem cells along one differentiation pathway can be induced. Controlled differentiation of stem cells will require the engineering of niches and extracellular signal combinations that would amplify a particular signaling network and allow uniform and selective differentiation. Three recent advances in stem cell research open the possibility to approach engineering studies for cell replacement therapies. Fusion events between stem cells and adult cells or between adult and embryonic stem cells have been shown to result in altered fates and nuclear reprogramming of cell hybrids. Hematopoietic stem cells were shown to require Wnt signaling in order to renew. The purification of Wnt proteins would allow their use as exogenous purified cytokines in attempts to amplify stem cells before bone marrow transplantation. The homeodomain protein Nanog has been shown to be crucial for the embryonic stem cell renewal and pluripotency. However, the cardinal question of how stemness is preserved in the early embryo and adult stem cells remains opened. [source]

Critical nucleation size in the folding of small apparently two-state proteins

PROTEIN SCIENCE, Issue 5 2004
Yawen Bai
Abstract For apparently two-state proteins, we found that the size (number of folded residues) of a transition state is mostly encoded by the topology, defined by total contact distance (TCD) of the native state, and correlates with its folding rate. This is demonstrated by using a simple procedure to reduce the native structures of the 41 two-state proteins with native TCD as a constraint, and is further supported by analyzing the results of eight proteins from protein engineering studies. These results support the hypothesis that the major rate-limiting process in the folding of small apparently two-state proteins is the search for a critical number of residues with the topology close to that of the native state. [source]