Systematic Review of Clinical and Pathophysiological Features of Genetic Creutzfeldt–Jakob Disease Caused by a Val-to-Ile Mutation at Codon 180 in the Prion Protein Gene

Genetic Creutzfeldt–Jakob disease (gCJD) is a subtype of genetic prion diseases (gPrDs) caused by the accumulation of mutated pathological prion proteins (PrP^Sc). gCJD has a phenotypic similarity with sporadic CJD (sCJD). In Japan, gCJD with a Val to Ile substitution at codon 180 (V180I-gCJD) is the most frequent gPrD, while the mutation is extremely rare in countries other than Japan and Korea. In this article, we aim to review previously elucidated clinical and biochemical features of V180I-gCJD, expecting to advance the understanding of this unique subtype in gCJD. Compared to classical sCJD, specific clinical features of V180I-gCJD include older age at onset, a relatively slow progression of dementia, and a lower positivity for developing myoclonus, cerebellar, pyramidal signs, and visual disturbance. Diffuse edematous ribboning hyperintensity of the cerebral cortex, without occipital lobes in diffusion-weighted magnetic resonance imaging, is also specific. Laboratory data reveal the low positivity of PrP^Sc in the cerebrospinal fluid and periodic sharp wave complexes on an electroencephalogram. Most patients with V180I-gCJD have been reported to have no family history, probably due to the older age at onset, and clinical and biochemical features indicate the specific phenotype associated with the prion protein gene mutation.     

Framework for Performance-Based Design of Building Structures

Abstract:   This article proposes a new framework for performance-based design (PBD) of building structures. This framework was proposed under the 3-year Japanese Government Comprehensive Research and Development Project on "Development of a New Engineering Framework for Building Structures" launched in the fiscal year of 1995. The primary objective of the project is to create a system in which the performance of buildings is clearly stated, and consumers, that is, occupants, are well informed of how their buildings will perform and how much it will cost to maintain their performance. The framework emphasizes the establishment of target performance, the performance evaluation, and the performance statement as the main three elements. It also stresses that an institutional framework and support systems need to be provided to enable PBD to be practiced efficiently. The implementation of the proposed framework is also expected to promote engineering innovation, progress in building engineering, and globalization. The new framework will also bring other benefits, such as improved design techniques, greater design flexibility, and international harmonization. It is also important for building structural performance to become one of the most important indexes for consumers to define a building's value. The Japanese building code was changed to the performance-based code, based in the clear and comprehensive manner proposed in this article. In the United States, "Vision 2000" ( SEAOC, 1995 ) was published, then many research activities were conducted simultaneously.     

Albumin stabilizes (–)‐epigallocatechin gallate in human serum: Binding capacity and antioxidant property

(–)‐Epigallocatechin gallate (EGCg) is the major component of green tea and is known to show strong biological activity, although it can be easily oxidized under physiological conditions. In this study, we indicate that EGCg is stable in human serum and that human serum albumin (HSA) stabilizes EGCg under aerobic condition. Although EGCg is usually decomposed within 1 h in aqueous solution at neutral pH, EGCg in serum and phosphate buffer (pH 7.4) containing HSA was stable over 1 h, even at neutral and slightly alkaline pH. Under these conditions, EGCg binds to HSA non‐covalently. The sulfhydryl group acts as an antioxidant for EGCg oxidation. Incubation of EGCg with HSA is accompanied by the oxidation of a free sulfhydryl group in HSA. These results suggest that the antioxidant property and the binding capacity of HSA contribute to the stabilization of EGCg in human serum.     

Comprehensive analysis of minimum grain size in pure aluminum using friction stir processing

A friction stir processing (FSP) technique has been developed for use with aluminum and magnesium alloys, with the goal of high-strain-rate processing. In this study, we treat the microstructures of aluminum samples, of three levels of purity, manipulating their grain sizes, making them finer, using FSP. Grain sizes decreased with an increase in the Zener-Hollomon parameter, at all purity levels. However, the recrystallized grain of FSP-ed ultra-high-purity (99.999%) aluminum was particularly large, compared to the grain sizes of lower-purity (99% and 99.99%) aluminum, when subjected to the same processing conditions. The grain size reached a certain minimum value at high-strain-rates of processing, which we report for each purity level herein.     

On an implicit stress-calculation algorithm for a multidimensional constitutive law using a skeleton curve

In this paper, we present an implicit stress-calculation algorithm for a multidimensional constitutive law using a one-dimensional skeleton curve and a hysteresis curve. To consider the hysteretic behavior of soils, one-dimension skeleton curves (e.g., the Hardin–Drnevich model, Ramberg–Osgood (RO) model, and general hyperbolic equation (GHE) model) are widely used. In a multidimensional analysis, there are several methods for extending a constitutive law using a skeleton curve into multiple dimensions. However, because these methods are suitable for an explicit integration stress-calculation scheme, a calculated stress does not satisfy the function of skeleton curve when a large incremental strain is imposed in one step. In this paper, to resolve this problem, a nonlinear stress–strain relation using a skeleton curve and an implicit stress-calculation algorithm is presented. In addition, we show an example of an application of the GHE/RO model to the proposed algorithm.     

A Single Mutation at the Ferredoxin Binding Site of P450 Vdh Enables Efficient Biocatalytic Production of 25‐Hydroxyvitamin D3

Vitamin D₃ hydroxylase (Vdh) from Pseudonocardia autotrophica is a cytochrome P450 monooxygenase that catalyzes the two‐step hydroxylation of vitamin D₃ (VD₃) to produce 25‐hydroxyvitamin D₃ (25(OH)VD₃) and 1α,25‐dihydroxyvitamin D₃ (1α,25(OH)₂VD₃). These hydroxylated forms of VD₃ are useful as pharmaceuticals for the treatment of conditions associated with VD₃ deficiency and VD₃ metabolic disorder. Herein, we describe the creation of a highly active T107A mutant of Vdh by engineering the putative ferredoxin‐binding site. Crystallographic and kinetic analyses indicate that the T107A mutation results in conformational change from an open to a closed state, thereby increasing the binding affinity with ferredoxin. We also report the efficient biocatalytic synthesis of 25(OH)VD₃, a promising intermediate for the synthesis of various hydroxylated VD₃ derivatives, by using nisin‐treated Rhodococcus erythropolis cells containing Vdh_T107A. The gene‐expression cassette encoding Bacillus megaterium glucose dehydrogenase‐IV was inserted into the R. erythropolis chromosome and expressed to avoid exhaustion of NADH in a cytoplasm during bioconversion. As a result, approximately 573 μg mL^?1 25(OH)VD₃ was successfully produced by a 2 h bioconversion.