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In this paper, we investigate the interfacial behavior of a thin one-dimensional (1D) hexagonal quasicrystal (QC) film bonded on an elastic substrate subjected to a mismatch strain due to thermal variation. The contact interface is assumed to be non-slipping, with both perfectly bonded and debonded boundary conditions. The Fourier transform technique is adopted to establish the integral equations in terms of interfacial shear stress, which are solved as a linear algebraic system by approximating the unknown phonon interfacial shear stress via the series expansion of the Chebyshev polynomials. The expressions are explicitly obtained for the phonon interfacial shear stress, internal normal stress, and stress intensity factors (SIFs). Finally, based on numerical calculations, we briefly discuss the effects of the material mismatch, the geometry of the QC film, and the debonded length and location on stresses and SIFs. [ABSTRACT FROM AUTHOR]

In this paper, the three-dimensional (3D) interfacial fracture is analyzed in a one-dimensional (1D) hexagonal quasicrystal (QC) coating structure under mechanical loading. A planar interface crack with arbitrary shape is studied by a displacement discontinuity method. Fundamental solutions of interfacial concentrated displacement discontinuities are obtained by the Hankel transform technique, and the corresponding boundary integral-differential equations are constructed with the superposition principle. Green's functions of constant interfacial displacement discontinuities within a rectangular element are derived, and a boundary element method is proposed for numerical simulation. The singularity of stresses near the crack front is investigated, and the stress intensity factors (SIFs) as well as energy release rates (ERRs) are determined. Finally, relevant influencing factors on the fracture behavior are discussed. [ABSTRACT FROM AUTHOR]

The interface crack problems in the two-dimensional (2D) decagonal quasi-crystal (QC) coating are theoretically and numerically investigated with a displacement discontinuity method. The 2D general solution is obtained based on the potential theory. An analogy method is proposed based on the relationship between the general solutions for 2D decagonal and one-dimensional (1D) hexagonal QCs. According to the analogy method, the fundamental solutions of concentrated point phonon displacement discontinuities are obtained on the interface. By using the superposition principle, the hypersingular boundary integral-differential equations in terms of displacement discontinuities are determined for a line interface crack. Further, Green's functions are found for uniform displacement discontinuities on a line element. The oscillatory singularity near a crack tip is eliminated by adopting the Gaussian distribution to approximate the delta function. The stress intensity factors (SIFs) with ordinary singularity and the energy release rate (ERR) are derived. Finally, a boundary element method is put forward to investigate the effects of different factors on the fracture. [ABSTRACT FROM AUTHOR]

Background and purpose Investigation of the relationship between mitochondrial DNA (mt DNA) variants and Parkinson disease ( PD) remains an issue awaiting more supportive evidence. Moreover, an affirming cellular model study is also lacking. Methods The index mt DNA variants and their defining mitochondrial haplogroup were determined in 725 PD patients and 744 non- PD controls. Full-length mt DNA sequences were also conducted in 110 cases harboring various haplogroups. Cybrid cellular models, composed by fusion of mitochondria-depleted rho-zero cells and donor mitochondria, were used for a rotenone-induced PD simulation study. Results Multivariate logistic regression analysis revealed that subjects harboring the mitochondrial haplogroup B5 have resistance against PD (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002). Furthermore, a composite mt DNA variant group consisting of A10398G and G8584A at the coding region was found to have resistance against PD (odds ratio 0.50, 95% confidence interval 0.33-0.78; P = 0.001). In cellular studies, B4 and B5 cybrids were selected according to their higher resistance to rotenone, in comparison with cybrids harboring other haplogroups. The B5 cybrid, containing G8584A/A10398G variants, showed more resistance to rotenone than the B4 cybrid not harboring these variants. This is supported by findings of low reactive oxygen species generation and a low apoptosis rate in the B5 cybrid, whereas a higher expression of autophagy was observed in the B4 cybrid particularly under medium dosage and longer treatment time with rotenone. Conclusions Our studies, offering positive results from clinical investigations and cybrid experiments, provide data supporting the role of variant mt DNA in the risk of PD. [ABSTRACT FROM AUTHOR]

Most solid tumors undergo hypoxia, leading to rapid cell division, metastasis and expansion of a cell population with hallmarks of cancer stem cells (CSCs). Tumor-selective replication of oncolytic adenoviruses may be hindered by oxygen deprivation in tumors. It is desirable to develop a potent oncolytic adenovirus, retaining its antitumor activity even in a hypoxic environment. We have previously generated an Oct4-dependent oncolytic adenovirus, namely Ad9OC, driven by nine copies of the Oct4 response element (ORE) for specifically killing Oct4-overexpressing bladder tumors. Here, we developed a novel Oct4 and hypoxia dual-regulated oncolytic adenovirus, designated AdLCY, driven by both hypoxia response element (HRE) and ORE. We showed that hypoxia-inducible factor (HIF)-2α and Oct4 were frequently overexpressed in hypoxic bladder cancer cells, and HIF-2α was involved in HRE-dependent and Oct4 transactivation. AdLCY exhibited higher cytolytic activities than Ad9OC against hypoxic bladder cancer cells, while sparing normal cells. AdLCY exerted potent antitumor effects in mice bearing human bladder tumor xenografts and syngeneic bladder tumors. It could target hypoxic CD44- and CD133-positive bladder tumor cells. Therefore, AdLCY may have therapeutic potential for targeting hypoxic bladder tumors and CSCs. As Oct4 is expressed in various cancers, AdLCY may be further explored as a broad-spectrum anticancer agent. [ABSTRACT FROM AUTHOR]

Background: Antigen-specific human IgEs are important reagents in immunoassays to quantify antigen-specific IgEs in allergic patients, but they are not easy to prepare. Methods: We constructed a knockin homozygous mouse strain, referred to as HϵjKI strain, whose gene segment encoding γ1 constant region has been replaced by that encoding human κ constant region and gene segment encoding κ constant region replaced by that encoding human κ constant region. The mice were tested for their ability to produce antigen-specific chimeric human IgE (with mouse variable regions) upon the immunization with ovalbumin and papain. Subsequently, the spleen cells from the immunized mice were used as the source of B cells for the preparation of hybridomas, which secreted monoclonal human IgE antibodies specific for the antigens. Results: The HϵjKI mice expressed human IgE (ϵ, κ) in serum at levels 10- to 30-fold higher than those of mouse IgE. Upon immunization with an antigen, the mice yielded splenic B cells for preparing hybridomas that secrete chimeric human IgE specific for the antigen. Purified IgEs from those hybridomas could activate a basophilic cell line to undergo degranulation upon the stimulation with their respective antigens. Conclusions: We have developed a human ϵ gene and κ gene knockin mouse strain, which is useful for producing various antigen-specific chimeric human IgEs for potential use as standards in immunoassays. [ABSTRACT FROM AUTHOR]

Background and purpose Spastic paraplegia type 5 ( SPG5) is an autosomal recessive ( AR) hereditary spastic paraplegia ( HSP) associated with pure or complicated phenotypes. This study aimed to screen SPG5 in Taiwanese HSP patients. Methods Sequencing of the SPG5 gene, CYP7B1, was performed in a cohort of 25 ethnic Han Taiwanese patients with AR or sporadic HSP. Clinical information and magnetic resonance imaging ( MRI) were analyzed in confirmed SPG5 patients. Results One (33%) AR kindred and four (18%) sporadic cases had CYP7B1 mutations. All of the SPG5 cases carried the mutation c.334 C>T (R112X). Haplotype analysis suggested a 'founder effect' in ethnic Hans for this mutation. The phenotype was either pure or complicated by cerebellar ataxia. For the primary HSP phenotype, there were profound dorsal column sensory deficits in all patients. Spine MRI showed thoraco-lumbar cord atrophy in some patients. Conclusions Spastic paraplegia type 5 is a common cause of AR and sporadic HSPs that has a higher frequency in Taiwanese than in other ethnic groups. It is associated with a CYP7B1 founder mutation and its phenotype is characterized by pronounced dorsal column sensory loss, with cerebellar ataxia in some patients. [ABSTRACT FROM AUTHOR]

The control of secondary cooling is extremely important for the quality of billet in the continuous casting. In order to minimise the variation in surface temperature and excessive reheating of billet, which have a considerable influence on the formation of cracks and other defects, a real time heat transfer model that can be used for simulation of varying casting operations was developed. In order to verify the dynamic performance of this model, a charge coupled device temperature measurement system that can eliminate the impact of the scales was presented. The actual shell thickness profile and billet temperature were calculated in real time by this model online and were taken into account to feedback control the casting process based on the desired target cooling pattern to improve the existing cooling system. The dynamic control system based on this model was developed and implemented on some caster, and the billet quality was obviously improved. [ABSTRACT FROM AUTHOR]

(G2019S) mutation of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases. Twelve- to sixteen-month-old (G2019S) LRRK2 transgenic mice prepared by us displayed progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurons and parkinsonism phenotypes of motor dysfunction. LRRK2 is a member of mixed lineage kinase subfamily of mitogen-activated protein kinase kinase kinases (MAPKKKs). We hypothesized that (G2019S) mutation augmented LRRK2 kinase activity, leading to overphosphorylation of downstream MAPK kinase (MKK) and resulting in activation of neuronal death signal pathway. Consistent with our hypothesis, (G2019S) LRRK2 expressed in HEK 293 cells exhibited an augmented kinase activity of phosphorylating MAPK kinase 4 (MKK4) at Ser257, and protein expression of active phospho-MKK4Ser257 was upregulated in the SN of (G2019S) LRRK2 transgenic mice. Protein level of active phospho-JNKThr183/Tyr185 and phospho-c-JunSer63, downstream targets of phospho-MKK4Ser257, was increased in the SN of (G2019S) LRRK2 mice. Upregulated mRNA expression of pro-apoptotic Bim and FasL, target genes of phospho-c-JunSer63, and formation of active caspase-9, caspase-8 and caspase-3 were also observed in the SN of (G2019S) LRRK2 transgenic mice. Our results suggest that mutant (G2019S) LRRK2 activates MKK4-JNK-c-Jun pathway in the SN and causes the resulting degeneration of SNpc dopaminergic neurons in PD transgenic mice. [ABSTRACT FROM AUTHOR]

Background: There are few large-scale clinical analyses of essential tremor (ET) in Asia. We studied the detailed clinical profile with emphasizing the age of onset, tremor location, specific tremor patterns, and rate of progression (ROP) to delineate the characteristics of Taiwanese ET patients and found the difference between the Taiwanese and the Caucasians ET patients. Methods: All ET patients fulfilled the Movement Disorders Society diagnosis criteria were investigated with a standardized assessment protocol, which including clinical evaluation, uniform severity scoring, self-reported questionnaires, accelerometry, surface electromyography, and videotaped tremor examination. Results: Of 219 patients recruited from July 2008 to October 2009, 153 completed the study protocol. Their mean age was 58.9 years and 47% were women, and 33.3% had family history (FH). There was bimodal distribution in age of tremor onset in patients without but not in those with FH. Head tremor (HT) was present in 48 of 153 (31%) patients. Patients with HT showed slower tremor frequency and less ROP than those without HT. Sixty-seven (44%) patients presented with intention tremor (IT). Male gender and voice tremor were predictive factors of IT occurrence. Conclusions: Comparing with the Caucasians, Taiwanese ET patients have different patterns of onset-age distribution and lack of female predominance in ET with HT. However, patients with IT and without HT also progressed more rapid as found in the Caucasian. [ABSTRACT FROM AUTHOR]

Background and purpose: The association between glucocerebrosidase ( GBA) mutations and Parkinson's disease (PD) is attracting increased attention worldwide. In patients of Chinese ethnicity, other than the common L444P mutation, a few mutations have been reported. However, the contribution of GBA to PD can be answered only by a thorough investigation of its mutations in a unique large population. Methods: We enrolled 1747 participants: 967 PD patients and 780 healthy individuals. We screened entire GBA coding regions and exon-intron boundaries in 30 randomly chosen PD patients, followed by testing five variants (L444P, D409H, R120W, L174P, and Q497R) in all participants. The G2385R and R1628P in LRRK2 had been previously studied in almost all participants. Results: In total, 36 patients (3.72%) carried a heterozygous mutant GBA allele (27 L444P, 7 Rec NciI, and 2 D409H). Only two controls (0.26%) carried heterozygous GBA mutation (1 L444P and 1 Rec NciI). In PD group, the mean age at onset in carriers was younger than in non-carriers. The difference in percentage of mutation frequencies between patients and controls was highly significant for the L444P mutation ( P < 0.0001). One L444P carrier was also associated with LRRK2 G2385R variant, but no atypical Parkinsonism was observed. Conclusions: The present study ascertains that L444P mutation in GBA gene may contribute to an earlier onset of development of PD in Han/Chinese population. Following LRRK2 variants, GBA is the second most frequent mutations indicated for sporadic PD development in the Han/Chinese population. These GBA carriers are associated with an earlier onset of Parkinsonism. [ABSTRACT FROM AUTHOR]