Stereometric Design for Desk-Top SFF Fabrication

Solid Freeform Fabrication (SFF) technologies refer to the fabrication of physical parts directly from computer based solid models described by STL (Stereo Lithography) or VRML (Virtual Reality Modeling Language) files generated by Computer-Aided Design (CAD) systems. Most of the SFF processes produce parts by building them layer by layer using a row by row pattern, though it is possible to build the part using other patterns. The SFF technology represents a challenge to designers who, in addition to making decisions concerning optimum shape and functionality of the entire part, have'to take under consideration several other manufacturing factors. These factors cover a wide range of technical issues such as Computer-Aided Design model generation, part description and model slicing files, laser path files, precision of part design, rendering patterns, manufacturing tolerances, thermal expansion and residual stress phenomena. This paper investigates the effect of rendering patterns on the integrity, material characteristics and mechanical properties of the parts prepared by a desk-top SFF device using diode lasers. Fe - Bronze (Cu - Sn) premixed metal powders were used as the starting material. The particle size was about 100 /lm to 200 /lm. Density, tensile strength and microstructure of the parts prepared using different rendering patterns were characterized. The results were analyzed to seek optimal rendering patterns. It was noticed that the samples were strong along the laser scanning direction, while they were weak perpendicular to the scanning direction. These results suggest that the laser scanning patterns should be designed to minimize the warping and maximize the strength of the part in the direction depending on the part's function.Mechanical Engineerin

Universal Decimal Classification : a Unique Scheme with its Origin,Development and Credibility

this article deals with the emergence, background history and usages of the Universal Decimal Classification scheme(UDC).It also speaks about the influence of the very scheme over different languages in different countries.It focuses also on the scheme’s acceptability and flexibility to the universal users.This article discusses the scheme’s inclination to be transformed into a machine readable version to compete with other schemes full-fledgedly.Here, the significance of classification scheme in a multilingual atmosphere  is highlighted and future advancements delineated

Dehydrogenation studies in the field of indole alkaloids

Two methods of dehydrogenation have been used for the oxidation of variously ring E-substituted yohimbine- and ajmalicine-type indole alkaloids;The first method, palladium-maleic acid dehydrogenation, produces ring C tetradehydro compounds and can be used for differentiating pseudo compounds from epiallo compounds. The second method, mercuric acetate oxidation, produces 3-dehydro compounds;By the use of the first method the stereochemistry of several indole alkaloids was elucidated;Infrared spectra in the C-H stretching region (3.4--3.7mu) have been used for differentiating between C3 epimers of indole alkaloids;Structures were proposed for several new compounds derived by oxidation or reduction of indole alkaloids or their derivatives;The stereochemistry of various reduction methods was discussed

Mechanism of amyloid β-protein dimerization determined using single-molecule AFM force spectroscopy.

Aβ42 and Aβ40 are the two primary alloforms of human amyloid β-protein (Aβ). The two additional C-terminal residues of Aβ42 result in elevated neurotoxicity compared with Aβ40, but the molecular mechanism underlying this effect remains unclear. Here, we used single-molecule force microscopy to characterize interpeptide interactions for Aβ42 and Aβ40 and corresponding mutants. We discovered a dramatic difference in the interaction patterns of Aβ42 and Aβ40 monomers within dimers. Although the sequence difference between the two peptides is at the C-termini, the N-terminal segment plays a key role in the peptide interaction in the dimers. This is an unexpected finding as N-terminal was considered as disordered segment with no effect on the Aβ peptide aggregation. These novel properties of Aβ proteins suggests that the stabilization of N-terminal interactions is a switch in redirecting of amyloids form the neurotoxic aggregation pathway, opening a novel avenue for the disease preventions and treatments

Mechanism of amyloid β-protein dimerization determined using single-molecule AFM force spectroscopy.

Aβ42 and Aβ40 are the two primary alloforms of human amyloid β-protein (Aβ). The two additional C-terminal residues of Aβ42 result in elevated neurotoxicity compared with Aβ40, but the molecular mechanism underlying this effect remains unclear. Here, we used single-molecule force microscopy to characterize interpeptide interactions for Aβ42 and Aβ40 and corresponding mutants. We discovered a dramatic difference in the interaction patterns of Aβ42 and Aβ40 monomers within dimers. Although the sequence difference between the two peptides is at the C-termini, the N-terminal segment plays a key role in the peptide interaction in the dimers. This is an unexpected finding as N-terminal was considered as disordered segment with no effect on the Aβ peptide aggregation. These novel properties of Aβ proteins suggests that the stabilization of N-terminal interactions is a switch in redirecting of amyloids form the neurotoxic aggregation pathway, opening a novel avenue for the disease preventions and treatments

β-hairpin-mediated formation of structurally distinct multimers of neurotoxic prion peptides

Protein misfolding disorders are associated with conformational changes in specific proteins, leading to the formation of potentially neurotoxic amyloid fibrils. During pathogenesis of prion disease, the prion protein misfolds into β-sheet rich, protease-resistant isoforms. A key, hydrophobic domain within the prion protein, comprising residues 109–122, recapitulates many properties of the full protein, such as helix-to-sheet structural transition, formation of fibrils and cytotoxicity of the misfolded isoform. Using all-atom, molecular simulations, it is demonstrated that the monomeric 109–122 peptide has a preference for α-helical conformations, but that this peptide can also form β-hairpin structures resulting from turns around specific glycine residues of the peptide. Altering a single amino acid within the 109–122 peptide (A117V, associated with familial prion disease) increases the prevalence of β-hairpin formation and these observations are replicated in a longer peptide, comprising residues 106–126. Multi-molecule simulations of aggregation yield different assemblies of peptide molecules composed of conformationally-distinct monomer units. Small molecular assemblies, consistent with oligomers, comprise peptide monomers in a β-hairpin-like conformation and in many simulations appear to exist only transiently. Conversely, larger assemblies are comprised of extended peptides in predominately antiparallel β-sheets and are stable relative to the length of the simulations. These larger assemblies are consistent with amyloid fibrils, show cross-β structure and can form through elongation of monomer units within pre-existing oligomers. In some simulations, assemblies containing both β-hairpin and linear peptides are evident. Thus, in this work oligomers are on pathway to fibril formation and a preference for β-hairpin structure should enhance oligomer formation whilst inhibiting maturation into fibrils. These simulations provide an important new atomic-level model for the formation of oligomers and fibrils of the prion protein and suggest that stabilization of β-hairpin structure may enhance cellular toxicity by altering the balance between oligomeric and fibrillar protein assemblies

Cu(II) mediates kinetically distinct, non-amyloidogenic aggregation of amyloid-β peptides

Cu(II) ions are implicated in the pathogenesis of Alzheimer disease by influencing the aggregation of the amyloid-β (Aβ) peptide. Elucidating the underlying Cu(II)-induced Aβ aggregation is paramount for understanding the role of Cu(II) in the pathology of Alzheimer disease. The aim of this study was to characterize the qualitative and quantitative influence of Cu(II) on the extracellular aggregation mechanism and aggregate morphology of Aβ(1–40) using spectroscopic, microelectrophoretic, mass spectrometric, and ultrastructural techniques. We found that the Cu(II):Aβ ratio in solution has a major influence on (i) the aggregation kinetics/mechanism of Aβ, because three different kinetic scenarios were observed depending on the Cu(II):Aβ ratio, (ii) the metal:peptide stoichiometry in the aggregates, which increased to 1.4 at supra-equimolar Cu(II):Aβ ratio; and (iii) the morphology of the aggregates, which shifted from fibrillar to non-fibrillar at increasing Cu(II):Aβ ratios. We observed dynamic morphological changes of the aggregates, and that the formation of spherical aggregates appeared to be a common morphological end point independent on the Cu(II) concentration. Experiments with Aβ(1–42) were compatible with the conclusions for Aβ(1–40) even though the low solubility of Aβ(1–42) precluded examination under the same conditions as for the Aβ(1–40). Experiments with Aβ(1–16) and Aβ(1–28) showed that other parts than the Cu(II)-binding His residues were important for Cu(II)-induced Aβ aggregation. Based on this study we propose three mechanistic models for the Cu(II)-induced aggregation of Aβ(1–40) depending on the Cu(II):Aβ ratio, and identify key reaction steps that may be feasible targets for preventing Cu(II)-associated aggregation or toxicity in Alzheimer disease