Applying Geographically Weighted Regression to Conjoint Analysis: Empirical Findings from Urban Park Amenities

The objective of this study is to develop spatially-explicit choice model and investigate its validity and applicability in CA studies. This objective is achieved by applying locally-regressed geographically weighted regression (GWR) and GIS to survey data on hypothetical dogrun facilities (off-leash dog area) in urban recreational parks in Tokyo, Japan. Our results show that spatially-explicit conditional logit model developed in this study outperforms traditional model in terms of data fit and prediction accuracy. Our results also show that marginal willingness-to-pay for various attributes of dogrun facilities has significant spatial variation. Analytical procedure developed in this study can reveal spatially-varying individual preferences on attributes of urban park amenities, and facilitates area-specific decision makings in urban park planning.Choice experiments, conjoint analysis, dogrun, geographically weighted regression, spatial econometrics, Research Methods/ Statistical Methods, Resource /Energy Economics and Policy,

A novel nonsense mutation in the TITF-1 gene in a Japanese family with benign hereditary chorea

A Japanese family with a novel nonsense mutation in the TITF-1 gene (p.Y98X) is described. The proband showed severe generalized chorea, delayed motor development, subnormal intelligence, congenital hypothyroidism, bronchial asthma, and a history of pulmonary infection, all of which are characteristic features of Brain-Thyroid-Lung syndrome. On the other hand, her brother and mother showed a mild benign hereditary chorea (BHC) phenotype with congenital hypothyroidism. Intrafamilial phenotypic variation is common in BHC/Brain-Thyroid-Lung syndrome and suggests the existence of other genetic or environmental factors regulating TITF-1 function. Although choreic movement in BHC/Brain-Thyroid-Lung syndrome is recognized as non-progressive, the proband showed re-exacerbation of choreic movement at puberty. The dopamine agonist, ropinirole hydrochloride, reduced her choreic movements, suggesting that levodopa and/or dopamine agonists may compensate for underdeveloped dopaminergic pathways in this disorder.ArticleJOURNAL OF THE NEUROLOGICAL SCIENCES. 313(1-2):189-192 (2012)journal articl

Spinocerebellar ataxia type 6 (SCA6): Clinical pilot trial with gabapentin

The clinical effect of the GABAergic drug gabapentin was evaluated in 11 patients with spinocerebellar ataxia type 6 (SCA6). The total period of gabapentin treatment was 4 weeks, and outcome measures were determined with the International Cooperative Ataxia Rating Scales (ICARS) and postural sway studies. At week 4, 5 patients showed a decrease of the ICARS values by more than 10% compared with the pretreatment baseline. Eight patients showed a more than 10% decrease of the sway area (SA) and/or sway path length (SPL) values in postural sway Studies. The ICARS values and SA/SPL values were not necessarily consistent in each patient, but 3 patients showed a more than 10% decrease in the ICRAS, SA, and SPL values at week 4 when compared to the pre-treatment baseline. As a whole, the efficacy of gabapentin was not statistically confirmed in the 4-week trial because of the variation in efficacy in each patient, but the data are indicative that some SCA6 patients could benefit from gabapentin treatment.ArticleJOURNAL OF THE NEUROLOGICAL SCIENCES. 278(1-2):107-111 (2009)journal articl

Temperature-sensitive reaction intermediate of F1-ATPase

F1-ATPase is a rotary molecular motor that makes 120° stepping rotations, with each step being driven by a single-ATP hydrolysis. In this study, a new reaction intermediate of F1-ATPase was discovered at a temperature below 4°C, which makes a pause at the same angle in its rotation as when ATP binds. The rate constant of the intermediate reaction was strongly dependent on temperature with a Q10 factor of 19, implying that the intermediate reaction accompanies a large conformational change. Kinetic analyses showed that the intermediate state does not correspond to ATP binding or hydrolysis. The addition of ADP to the reaction mixture did not alter the angular position of the intermediate state, but specifically lengthened the time constant of this state. Conversely, the addition of inorganic phosphate caused a pause at an angle of +80° from that of the intermediate state. These observations strongly suggest that the newly found reaction intermediate is an ADP-releasing step

A novel nonsense mutation in a Japanese family with ataxia with oculomotor apraxia type 2 (AOA2)

We report a 67-year-old Japanese woman with ataxia with oculomotor apraxia type 2 (AOA2). She was born to consanguineous parents and showed a teenage onset, a slowly progressive cerebellar ataxia and sensory-motor neuropathy and an elevated level of serum alpha-fetoprotein (AFP). All of these clinical features were consistent with typical AOA2. She lacked oculomotor apraxia, as frequently observed in previously reported AOA2 patients. She was homozygous for a novel nonsense mutation, Glu385Ter (E385X), in the senataxin gene (SETX). To our knowledge, this is the fifth Japanese family with genetically confirmed AOA2. The mutations in SETX in Japanese AOA2 families are heterogeneous, except for M274I, which has been found in two unrelated families. More extensive screening by serum AFP followed by molecular genetic analysis of SETX in patients with Friedreich's ataxia-like phenotype may show that AOA2 is more common in Japan than previously thought. Journal of Human Genetics (2009) 54, 746-748; doi: 10.1038/jhg.2009.104; published online 6 November 2009ArticleJOURNAL OF HUMAN GENETICS. 54(12):746-748 (2009)journal articl

Subcutaneous injection, from birth, of epigallocatechin-3-gallate, a component of green tea, limits the onset of muscular dystrophy in mdx mice: a quantitative histological, immunohistochemical and electrophysiological study

Dystrophic muscles suffer from enhanced oxidative stress. We have investigated whether administration of an antioxidant, epigallocatechin-3-gallate (EGCG), a component of green tea, reduces their oxidative stress and pathophysiology in mdx mice, a mild phenotype model of human Duchenne-type muscular dystrophy. EGCG (5mg/kg body weight in saline) was injected subcutaneously 4× a week into the backs of C57 normal and dystrophin-deficient mdx mice for 8weeks after birth. Saline was injected into normal and mdx controls. EGCG had almost no observable effects on normal mice or on the body weights of mdx mice. In contrast, it produced the following improvements in the blood chemistry, muscle histology, and electrophysiology of the treated mdx mice. First, the activities of serum creatine kinase were reduced to normal levels. Second, the numbers of fluorescent lipofuscin granules per unit volume of soleus and diaphragm muscles were significantly decreased by about 50% compared to the numbers in the corresponding saline-treated controls. Third, in sections of diaphragm and soleus muscles, the relative area occupied by histologically normal muscle fibres increased significantly 1.5- to 2-fold whereas the relative areas of connective tissue and necrotic muscle fibres were substantially reduced. Fourth, the times for the maximum tetanic force of soleus muscles to fall by a half increased to almost normal values. Fifth, the amount of utrophin in diaphragm muscles increased significantly by 17%, partially compensating for the lack of dystrophin expressio

Rikkunshito Ameliorates Cancer Cachexia Partly through Elevation of Glucarate in Plasma

Cancer cachexia, which is characterized by decreased food intake, weight loss and systemic inflammation, increases patient’s morbidity and mortality. We previously showed that rikkunshito (RKT), a Japanese traditional herbal medicine (Kampo), ameliorated the symptoms of cancer cachexia through ghrelin signaling-dependent and independent pathways. To investigate other mechanisms of RKT action in cancer cachexia, we performed metabolome analysis of plasma in a rat model bearing the Yoshida AH-130 hepatoma. A total of 110 metabolites were detected in plasma and RKT treatment significantly altered levels of 23 of those metabolites in cachexia model rats. Among them, glucarate, which is known to have anticarcinogenic activity through detoxification of carcinogens via inhibition of β-glucuronidase, was increased in plasma following administration of RKT. In our AH-130 ascites-induced cachexia rat model, administration of glucarate delayed onset of weight loss, improved muscle atrophy, and reduced ascites content. Additionally, glucarate reduced levels of plasma interferon-γ (IFN-γ) in tumor-bearing rats and was also found to suppress LPS-induced IFN-γ expression in splenocytes in vitro. These results suggest that glucarate has anti-inflammatory activity via a direct effect on immune host cells and suggest that RKT may also ameliorate inflammation partly through the elevation of glucarate in plasma

Detection of Lung Cancer Cells in Solutions Using a Terahertz Chemical Microscope

Cancer genome analysis has recently attracted attention for personalized cancer treatment. In this treatment, evaluation of the ratio of cancer cells in a specimen tissue is essential for the precise analysis of the genome. Conventionally, the evaluation takes at least two days and depends on the skill of the pathologist. In our group, a terahertz chemical microscope (TCM) was developed to easily and quickly measure the number of cancer cells in a solution. In this study, an antibody was immobilized on a sensing plate using an avidin-biotin reaction to immobilize it for high density and to improve antibody alignment. In addition, as the detected terahertz signals vary depending on the sensitivity of the sensing plate, the sensitivity was evaluated using pH measurement. The result of the cancer cell detection was corrected using the result of pH measurement. These results indicate that a TCM is expected to be an excellent candidate for liquid biopsies in cancer diagnosis