Catechol-O-methyltransferase and Parkinson's disease.

Parkinson's disease (PD) is one of the main causes of neurological disability in the elderly. Levodopa is the gold standard for treating this disease, but chronic levodopa therapy is complicated by motor fluctuation and dyskinesia. The catechol-O-methyltransferase (COMT) inhibitors represent a new class of antiparkinsonian drugs. When coadministered with levodopa/decarboxylase inhibitor, 2 COMT inhibitors, tolcapone and entacapone have been shown to improve the clinical benefit of levodopa. COMT activity is genetically polymorphic, and individuals with the low activity (COMT(L/L)) genotype have a thermolabile COMT protein; studies suggest that this genotype is less common in Asians than in Caucasians. Differences in COMT activity may determine the individual response to levodopa and result in ethnic differences in PD susceptibility. Our recent study suggests that the COMTL allele can interact with the MAOB gene to increase the occurrence of PD in Taiwanese. In order to understand this new class of antiparkinsonian drugs, we review their basic properties, pharmacology, and clinical efficacy. The frequency distribution of COMT genetic polymorphisms among different populations and its implications in the etiology and drug response is also discussed.</p

The Impacts Of Presentation Modes And Product Involvements On “Line” Short Message Service (SMS) Advertising Effectiveness

In today’s ubiquitous commerce (UC) era, short message service (SMS) advertisement has played an important role in the world of marketing. Convenience and economical reasons influence SMS usage frequency along with social involvement to influence attitudes towards SMS advertising. SMS advertising creates numerous opportunities for the marketers in promoting their products effectively. Adopting the competition for attention theory as the theoretical framework, we developed hypotheses to investigate the influences of presentation mode and involvement on SMS advertising performance (recall of advertising information). An experiment was conducted to examine the effects of three types of information presentation modes (text-only, image-text, and emoji-text) in the contexts of two product types (high- versus low-involvement products) in the “LINE” SMS environment. Specifically, in this current study, we allocate participants to six experimental environments (text-only for high-involvement products, text-only for low-involvement products, image-text for high-involvement products, image-text for low-involvement products, emoji-text for high-involvement products and emoji-text for low-involvement products) randomly to collected empirical data to examine the proposed hypotheses. The research findings are expected to provide instrumental guidelines for the practitioners to better achieve the goals of ads in the “LINE” SMS environment. Also, the empirical results may provide insights into the research of advertising interface design of SMS and integrating efforts from cognitive science and vision research to understand users’ involvement of SMS advertising processes

Simplified ZrTiOx-based RRAM cell structure with rectifying characteristics by integrating Ni/n + -Si diode

A simplified one-diode one-resistor (1D1R) resistive switching memory cell that uses only four layers of TaN/ZrTiO( x )/Ni/n(+)-Si was proposed to suppress sneak current where TaN/ZrTiO( x )/Ni can be regarded as a resistive-switching random access memory (RRAM) device while Ni/n(+)-Si acts as an Schottky diode. This is the first RRAM cell structure that employs metal/semiconductor Schottky diode for current rectifying. The 1D1R cell exhibits bipolar switching behavior with SET/RESET voltage close to 1 V without requiring a forming process. More importantly, the cell shows tight resistance distribution for different states, significantly rectifying characteristics with forward/reverse current ratio higher than 10(3) and a resistance ratio larger than 10(3) between two states. Furthermore, the cell also displays desirable reliability performance in terms of long data retention time of up to 10(4) s and robust endurance of 10(5) cycles. Based on the promising characteristics, the four-layer 1D1R structure holds the great potential for next-generation nonvolatile memory technology

Novel variant Pro143Ala in HTRA2 contributes to Parkinson’s disease by inducing hyperphosphorylation of HTRA2 protein in mitochondria

Mutations in the gene encoding the mitochondrial protein high temperature requirement A2 (HTRA2) are inconsistently associated with a risk of Parkinson’s disease (PD). We assessed the presence of HTRA2 mutations among patients with PD and performed functional assay of identified mutations or variants. Among the total 1,373 subjects, the entire HTRA2 coding region was sequenced in 113 early-onset PD (EOPD), 20 familial PD patients and 150 control subjects. An additional 390 sporadic late-onset PD patients and 700 controls were subsequently screened to validate possible mutations found in the first set. We identified two novel heterozygous variants, c.427C > G (Pro143Ala) and c.906 +3 G > A, in 2 (1.5%) EOPD patients. The missense variant, Pro143Ala, was also observed in one late-onset PD patient but was absent in total 850 control subjects (relative risk 2.3, 95% CI 1.5–2.8, P = 0.04). Expressing Pro143Ala variant of HTRA2 in primary dopaminergic neurons causes neurite degeneration. Following exposure to rotenone, the ultra-structural mitochondrial abnormality, the percentage of mitochondrial dysfunction and apoptosis in cells carrying the HTRA2 Pro143Ala variant was significantly higher than wild-type cells. Mechanistically, protein level of phosphorylated HTRA2 was increased in cells carrying the Pro143Ala variant, suggesting Pro143Ala variant promotes HTRA2 phosphorylation with resultant mitochondrial dysfunction. Our results support a biologically relevant role of HTRA2 in PD susceptibility in Taiwanese. Further large-scale association studies are warranted to confirm the role of HTRA2 Pro143Ala variant in the risk of PD

Can Variational Quantum Algorithms Demonstrate Quantum Advantages? Time Really Matters

Applying low-depth quantum neural networks (QNNs), variational quantum algorithms (VQAs) are both promising and challenging in the noisy intermediate-scale quantum (NISQ) era: Despite its remarkable progress, criticisms on the efficiency and feasibility issues never stopped. However, whether VQAs can demonstrate quantum advantages is still undetermined till now, which will be investigated in this paper. First, we will prove that there exists a dependency between the parameter number and the gradient-evaluation cost when training QNNs. Noticing there is no such direct dependency when training classical neural networks with the backpropagation algorithm, we argue that such a dependency limits the scalability of VQAs. Second, we estimate the time for running VQAs in ideal cases, i.e., without considering realistic limitations like noise and reachability. We will show that the ideal time cost easily reaches the order of a 1-year wall time. Third, by comparing with the time cost using classical simulation of quantum circuits, we will show that VQAs can only outperform the classical simulation case when the time cost reaches the scaling of $10^0$-$10^2$ years. Finally, based on the above results, we argue that it would be difficult for VQAs to outperform classical cases in view of time scaling, and therefore, demonstrate quantum advantages, with the current workflow. Since VQAs as well as quantum computing are developing rapidly, this work does not aim to deny the potential of VQAs. The analysis in this paper provides directions for optimizing VQAs, and in the long run, seeking more natural hybrid quantum-classical algorithms would be meaningful.Comment: 18 pages, 7 figure

Staphylococcal Cassette Chromosome mec in MRSA, Taiwan

To determine the predominant staphylococcal cassette chromosome (SCC) mec element in methicillin-resistant Staphylococcus aureus, we typed 190 isolates from a hospital in Taiwan. We found a shift from type IV to type III SCCmec element during 1992–2003, perhaps caused by selective pressure from indiscriminate use of antimicrobial drugs

Positive Effect of Severe Nakagami- m

This paper investigates the positive effect of severe Nakagami-m fading on the performance of multiuser transmit antenna selection/maximal-ratio combining (TAS/MRC) systems with high selection gain. Both amount of fading (AF) and symbol error rate (SER) of M-QAM are derived as closed-form expressions for integer m. For arbitrary m, the AF and the SER are expressible as a single infinite series of Gamma function and Gauss hypergeometric function, respectively. The analytical results lead to the following observations. First, the SER performance can demonstrate the positive effect of severe Nakagami-m fading on multiuser TAS/MRC systems with high selection gain. Second, the AF performance only exhibits the negative impact of severe fading regardless of high selection gain. Last, the benefit of severe fading to the system performance diminishes at high signal-to-noise ratio (SNR)

The study on the structure of exotic states χc1(3872)\chi_{c 1}(3872) via beauty-hadron decays in pppp collisions at s=8 TeV\sqrt{s}=8\,\mathrm{TeV}

A dynamically constrained phase-space coalescence (DCPC) model was introduced to study the exotic state $\chi_{c 1}(3872)$ yield for three possible structures: tetraquark state, nuclear-like state, and molecular state respectively, where the hadronic final states generated by the parton and hadron cascade model (PACIAE). The $\chi_{c 1}(3872)$/$\psi (2S)$ cross-section ratio from beauty-hadron decays (non-prompt) based on the $\chi_{c 1}(3872)$ or $\psi (2S)\to J/\psi{\pi^+}{\pi^-}$ bound state in the decay chains as a function of charged-particle multiplicity and transverse momentum in $pp$ collisions at $\sqrt{s}=8\,\mathrm{TeV}$ are calculated. A tetraquark state scenario from PACIAE+DCPC model shows better agreement with the LHCb and ATLAS measurements for the non-prompt $\chi_{c 1}(3872)$/$\psi(2S)$ cross-section ratio distributions, indicating that the $\chi_{c 1}(3872)$ is more likely to be a compact tetraquark state