Numerical modelling of semi-adiabatic test

The paper deals with the possibility of using a semi-adiabatic test to determine the adiabatic hydration curve of concrete mixtures. Therefore, a temperature was measured at certain points of a concrete specimen during the test and an adiabatic temperature rise was estimated with a numerically determined heat loss compensation. The determined adiabatic hydration curve was inserted into a numerical program, which is used to calculate a temperature field within the concrete element using a finite element method. A comparison between numerically and experimentally determined values indicates the adequacy of the proposed numerical model. Moreover, the semi-adiabatic test proved to be an appropriate method to determine the adiabatic temperature rise

Probing Early Misfolding Events in Prion Protein Mutants by NMR Spectroscopy

The post-translational conversion of the ubiquitously expressed cellular form of the prion protein, PrPC, into its misfolded and pathogenic isoform, known as prion or PrPSc, plays a key role in prion diseases. These maladies are denoted transmissible spongiform encephalopathies (TSEs) and affect both humans and animals. A prerequisite for understanding TSEs is unraveling the molecular mechanism leading to the conversion process whereby most \u3b1-helical motifs are replaced by \u3b2-sheet secondary structures. Importantly, most point mutations linked to inherited prion diseases are clustered in the C-terminal domain region of PrPC and cause spontaneous conversion to PrPSc. Structural studies with PrP variants promise new clues regarding the proposed conversion mechanism and may help identify "hot spots" in PrPC involved in the pathogenic conversion. These investigations may also shed light on the early structural rearrangements occurring in some PrPC epitopes thought to be involved in modulating prion susceptibility. Here we present a detailed overview of our solution-state NMR studies on human prion protein carrying different pathological point mutations and the implications that such findings may have for the future of prion research

New numerical procedure for the prediction of temperature development in early age concrete structures

A new numerical model for the prediction of temperature development in young concrete structures is briefly presented. With the pre-program. adiabatic hydration curves, which are used to determine the internal heat generation, are calculated. An artificial neural networks approach is used for this purpose. Adiabatic hydration curves, which were included in the learning set, were determined by our own experiments, using the adiabatic calorimeter which uses air as the coupling media. The main program is implemented in the finite element code. This program allows concrete structure designers and contractors to quantify and evaluate the effects of some concrete initial parameters on the adiabatic hydration curves and corresponding temperature development at an arbitrary point in the concrete element. Some examples are also presented and discussed. (C) 2009 Elsevier B.V. All rights reserve

NMR Structure of the Human Prion Protein with the Pathological Q212P Mutation Reveals Unique Structural Features

Prion diseases are fatal neurodegenerative disorders caused by an aberrant accumulation of the misfolded cellular prion protein (PrPC) conformer, denoted as infectious scrapie isoform or PrPSc. In inherited human prion diseases, mutations in the open reading frame of the PrP gene (PRNP) are hypothesized to favor spontaneous generation of PrPSc in specific brain regions leading to neuronal cell degeneration and death. Here, we describe the NMR solution structure of the truncated recombinant human PrP from residue 90 to 231 carrying the Q212P mutation, which is believed to cause Gerstmann-Sträussler-Scheinker (GSS) syndrome, a familial prion disease. The secondary structure of the Q212P mutant consists of a flexible disordered tail (residues 90–124) and a globular domain (residues 125–231). The substitution of a glutamine by a proline at the position 212 introduces novel structural differences in comparison to the known wild-type PrP structures. The most remarkable differences involve the C-terminal end of the protein and the β2–α2 loop region. This structure might provide new insights into the early events of conformational transition of PrPC into PrPSc. Indeed, the spontaneous formation of prions in familial cases might be due to the disruptions of the hydrophobic core consisting of β2–α2 loop and α3 helix

Numerical modelling of semi-adiabatic test

The paper deals with the possibility of using a semi-adiabatic test to determine the adiabatic hydration curve of concrete mixtures. Therefore, a temperature was measured at certain points of a concrete specimen during the test and an adiabatic temperature rise was estimated with a numerically determined heat loss compensation. The determined adiabatic hydration curve was inserted into a numerical program, which is used to calculate a temperature field within the concrete element using a finite element method. Acomparison between numerically and experimentally determined values indicatesthe adequacy of the proposed numerical model. Moreover, the semi-adiabatic test proved to be an appropriate method to determine the adiabatic temperature rise.The paper deals with the possibility of using a semi-adiabatic test to determine the adiabatic hydration curve of concrete mixtures. Therefore, a temperature was measured at certain points of a concrete specimen during the test and an adiabatic temperature rise was estimated with a numerically determined heat loss compensation. The determined adiabatic hydration curve was inserted into a numerical program, which is used to calculate a temperature field within the concrete element using a finite element method. A comparison between numerically and experimentally determined values indicates the adequacy of the proposed numerical model. Moreover, the semi-adiabatic test proved to be an appropriate method to determine the adiabatic temperature rise

Structural features of human prion protein variants revealed by NMR

Prion diseases are a group of fatal neurodegenerative disorders that can be of sporadic, genetic or acquired origin. The key molecular event in prion diseases is the conformational conversion of the physiological cellular prion protein, PrPC, into a disease-associated form, prion or PrPSc (scrapie PrP). Understanding of the earliest stages of the conformational changes leading to spontaneous generation of prions in genetic prion diseases, which are linked with mutations in the human prion protein gene, may benefit from structural characterization of various human (Hu) PrP variants. We determined NMR structures of the truncated recombinant HuPrPs (residues 90-231) with pathological Q212P [1] and V210I [2] mutations associated with Gerstmann- Str\ue4ussler-Scheinker (GSS) syndrome and familial Creutzfeldt-Jakob disease (CJD), respectively, and of HuPrP with naturally occurring E219K polymorphism [3] considered to act protectively against sporadic CJD. Comparison of 3D structures of HuPrP variants with the WT HuPrP revealed that mutations do not affect global architecture of the protein. However, 3D structures of HuPrPs with pathological Q212P and V210I mutations highlighted several common structural perturbations. These include disruption of hydrophobic contacts at the \u3b12-\u3b13 inter-helical interface, loosening of tertiary contacts between the \u3b22-\u3b12 loop and the C-terminus of helix \u3b13 and increased exposure of hydrophobic residues to solvent. In addition, we determined NMR structure of HuPrP(V210I) under physiological pH conditions which was found to exhibit higher structural stability when compared to the structure of the same protein at pH 5.5 [4]