Mutations in the enzyme superoxide dismutase 1 (SOD1) initiate a progressive motoneurone degeneration in amyotrophic lateral
sclerosis (ALS). Transgenic mice overexpressing this mutation develop a ...similar progressive motoneurone degeneration. In spinal
motoneurones cultured from presymptomatic mice expressing the glycine to alanine mutation at base pair 93 (G93A) SOD1 mutation,
a marked increase in the persistent component of the Na + current was observed, without changes in passive properties. This increase only enhanced neuronal excitability in high input
conductance cells, as low input conductance cells exhibited a compensatory outward shift in the current remaining after Na + blockade. High input conductance motoneurones tend to be large, so these results may explain the tendency of large motoneurones
to degenerate first in ALS. Riluzole, at the therapeutic concentration used to treat ALS, decreased neuronal excitability
and persistent Na + current in G93A motoneurones to levels observed in the control motoneurones. Aberrations in the intrinsic electrical properties
may be among the first symptoms to emerge in SOD1-linked ALS.
The paper considers the task of recognizing environmental sounds for the understanding of a scene or context surrounding an audio sensor. A variety of features have been proposed for audio ...recognition, including the popular Mel-frequency cepstral coefficients (MFCCs) which describe the audio spectral shape. Environmental sounds, such as chirpings of insects and sounds of rain which are typically noise-like with a broad flat spectrum, may include strong temporal domain signatures. However, only few temporal-domain features have been developed to characterize such diverse audio signals previously. Here, we perform an empirical feature analysis for audio environment characterization and propose to use the matching pursuit (MP) algorithm to obtain effective time-frequency features. The MP-based method utilizes a dictionary of atoms for feature selection, resulting in a flexible, intuitive and physically interpretable set of features. The MP-based feature is adopted to supplement the MFCC features to yield higher recognition accuracy for environmental sounds. Extensive experiments are conducted to demonstrate the effectiveness of these joint features for unstructured environmental sound classification, including listening tests to study human recognition capabilities. Our recognition system has shown to produce comparable performance as human listeners.
Summary
Background
The prevalence of allergic diseases has increased in the past decades. It is unknown whether expression of certain microRNAs (miRNAs) in neonatal leucocytes is correlated to IgE ...production and/or allergic diseases.
Objective
This study investigated the association of miRNA expression in neonatal leucocytes with cord blood IgE (CBIgE) elevation and development of allergic disease.
Methods
We screened for the expression of a panel of 157 miRNAs in mononuclear leucocytes from human umbilical cord blood (CB) samples with elevated CBIgE and tracked the association of down‐regulated miRNA expression to the miRNA‐targeted gene expression and to children with allergic rhinitis (AR).
Results
Among the initial screen of 10 CB samples with elevated CBIgE, expression of eight of the 157 miRNAs was low. Of these eight down‐expressed miRNAs, three remained down‐regulation in a validation with other 20 CB samples, and two of the three miRNAs, miR‐21 and miR‐126, were significantly lower in monocytes from AR children. Further analysis of mRNA expression of the miR‐21‐targeted genes identified that TGFBR2 expression on monocytes was significantly up‐regulated in CB with elevated CBIgE, and in AR patients. Transfection of miR‐21 precursor into monocytes from patients with AR increased miR‐21 expression and decreased TGFBR2 expression.
Conclusion
This study demonstrated the first in the literature that lower miR‐21 expression in CB and increased TGFBR2 expression is associated with antenatal IgE production and development of AR.
Cite this as: R.‐F. Chen, H.‐C. Huang, C.‐Y. Ou, T.‐Y. Hsu, H. Chuang, J.‐C. Chang, L. Wang, H.‐C. Kuo and K. D. Yang, Clinical & Experimental Allergy, 2010 (40) 1482–1490.
Orthogonal frequency division multiple access (OFDMA) has recently attracted vast research attention from both academia and industry and has become part of new emerging standards for broadband ...wireless access. Even though the OFDMA concept is simple in its basic principle, the design of a practical OFDMA system is far from being a trivial task. Synchronization represents one of the most challenging issues and plays a major role in the physical layer design. The goal of this paper is to provide a comprehensive survey of the latest results in the field of synchronization for OFDMA systems, with tutorial objectives foremost. After quantifying the effects of synchronization errors on the system performance, we review some common methods to achieve timing and frequency alignment in a downlink transmission. We then consider the uplink case, where synchronization is made particularly difficult by the fact that each user's signal is characterized by different timing and frequency errors, and the base station has thus to estimate a relatively large number of unknown parameters. A second difficulty is related to how the estimated parameters must be employed to correct the uplink timing and frequency errors. The paper concludes with a comparison of the reviewed synchronization schemes in an OFDMA scenario inspired by the IEEE 802.16 standard for wireless metropolitan area networks.
In this paper, we propose a cascaded sparse/DCT (S/DCT) two-layer representation of prediction residuals, and implement this idea on top of the state-of-the-art high efficiency video coding (HEVC) ...standard. First, a dictionary is adaptively trained to contain featured patterns of residual signals so that a high portion of energy in a structured residual can be efficiently coded via sparse coding. It is observed that the sparse representation alone is less effective in the R-D performance due to the side information overhead at higher bit rates. To overcome this problem, the DCT representation is cascaded at the second stage. It is applied to the remaining signal to improve coding efficiency. The two representations successfully complement each other. It is demonstrated by experimental results that the proposed algorithm outperforms the HEVC reference codec HM5.0 in the Common Test Condition.
Background and Purpose
The aim of this study was to determine the potency and molecular mechanism of action of YM155, a first‐in‐class survivin inhibitor that is currently under phase I/II clinical ...investigations, in various drug‐resistant breast cancers including the oestrogen receptor positive (ER+) tamoxifen‐resistant breast cancer and the caspase‐3‐deficient breast cancer.
Experimental Approach
The potency of YM155 in SK‐BR‐3, MDA‐MB‐231, MCF7 and its tamoxifen‐resistant sublines, TamR6, TamR7, TamR8, TamC3 and TamC6, were determined by MTT assay. Western blot analysis, flow cytometric analysis, reverse transcription‐PCR, fluorescent microscopy and comet assay were used to determine the molecular mechanism of action of YM155 in different breast cancer cell lines.
Key Results
YM155 was equally potent towards the parental ER+/caspase‐3‐deficient MCF7 breast cancer cells and its tamoxifen‐resistant sublines in vitro. The ER−/HER2+ SK‐BR‐3 breast cancer cells and the triple‐negative/caspase‐3‐expressing metastatic aggressive MDA‐MB‐231 breast cancer cells were also sensitive to YM155 with IC50 values in the low nanomolar range. Targeting survivin by YM155 modulated autophagy, induced autophagy‐dependent caspase‐7 activation and autophagy‐dependent DNA damage in breast cancer cells. Interestingly, YM155 also induced XIAP degradation and the degradation of XIAP might play an important role in YM155‐induced autophagy in breast cancer cells.
Conclusions and Implications
YM155 is a potent survivin inhibitor that has potential for the management of various breast cancer subtypes regardless of the expression of ER, HER2 and caspase‐3. Importantly, this study provides new insights into YM155's molecular mechanism of action and therapeutic potential in the treatment of tamoxifen‐resistant breast cancer.
Simple-but-precise evaluation of cerebral perfusion is crucial for the treatment of Moyamoya disease. We aimed to develop a standardized scoring system for MR perfusion suitable for Moyamoya disease ...evaluation and investigate the postoperative serial changes and outcome predictors.
From January 2013 to December 2016, patients diagnosed with Moyamoya disease and receiving indirect revascularization were recruited prospectively. Clinical data and serial imaging studies were analyzed. The TTP maps were standardized using cerebellar reference values. We developed a scoring system of standardized TTP maps: 14 points for each hemisphere with higher points indicating better perfusion.
In total, 24 children (4-17 years of age, 41 hemispheres) and 20 adults (18-51 years of age, 34 hemispheres) were included. The mean preoperative TTP scores were higher in children (7.34 ± 3.90) than in adults (4.88 ± 3.24). The standardized TTP maps revealed dynamic improvement with an increase in the corresponding scores at the 1-, 3-, and 6-month postoperative follow-ups; the scores stabilized after 6 months. The mean improvement in the 6-month scores of the pediatric and adult groups was 4.15 ± 3.55 and 6.03 ± 3.04, respectively. The 6-month TTP score improvements were associated with Matsushima grades. If we took score improvement as the outcome, the preoperative TTP score was the only significant predictor in multivariable analysis.
The standardized TTP maps and scoring system facilitated the quantification of the sequential perfusion changes during Moyamoya disease treatment. The preoperative perfusion status was the only predictor of indirect revascularization outcome.
Background and purpose
Our purpose was to determine the association of cataract surgery with subsequent development of dementia in older adults with newly diagnosed cataract.
Methods
By using data ...from Taiwan National Health Insurance Research Database (NHIRD), a population‐based cohort study including 491 226 subjects aged 70 or older with first‐time diagnosis of cataract coded from 2000 to 2009 was conducted. After matching cataract patients receiving cataract surgery with cataract patients without receiving cataract surgery for age, sex, index date, Charlson Comorbidity Index score, interval between first coding of cataract diagnosis and index date, hypertension and diabetes mellitus, 113 123 patients in each cohort were enrolled. The main outcome measure was newly diagnosed dementia coded by neurologists or psychiatrists more than 365 days after cataract surgery. Incidence rate and hazard ratio of dementia were compared between the cataract surgery and cataract diagnosis cohorts.
Results
The incidence rate of dementia was 22.40 per 1000 person‐years in the cataract surgery cohort and 28.87 per 1000 person‐years in the cataract diagnosis cohort. The rate of dementia was significantly lower in the cataract surgery group (hazard ratio 0.77, 95% confidence interval 0.75−0.79, P < 0.001). Female gender (P < 0.001) and a shorter interval between the date of first coding of a cataract diagnosis and the date of cataract surgery (P = 0.009) were significantly associated with a lower incidence rate of dementia.
Conclusion
In an NHIRD cohort of Taiwanese aged 70 years and older with a diagnosis of cataract, patients undergoing cataract surgery were associated with a reduced risk of subsequent dementia compared with those without cataract surgery.
We tested how lateral stability affects gait as a function of age. A simple computational model suggests that walking is laterally unstable and that age-related decreases in motor and sensory ...function may be treated as noise-like perturbations to the body. Step width variability may be affected by active control of foot placement subject to noise. We hypothesized that age-related deficits may lead to increased step width variability. A possible compensation would be to walk with wider steps to reduce the lateral instability. The addition of external stabilization, through elastic cords acting laterally on the body during treadmill walking, would be expected to yield reduced step width variability and/or reduced average step width. We measured step width, its variability (defined as standard deviation), and metabolic energy expenditure in eight adult human subjects aged less than 30 years (young) and ten subjects aged at least 65 years (old). Subjects walked with and without external stabilization, each at a self-selected step width as well as a prescribed step width of zero. In normal walking, old subjects preferred 41% wider steps than young, and expended 26% more net energy (P < 0.05). External stabilization caused both groups to prefer 58% narrower steps. In the prescribed zero step width condition, old subjects walked with 52% more step width variability and at 20% higher energetic cost. External stabilization resulted in reduced step width variability and 16% decreased energetic cost. Although there was no significant statistical interaction between age group and stabilization, old and young subjects walked with similar energetic costs in the stabilized, prescribed step width condition. Age-related changes appear to affect lateral balance, and the resulting compensations explain much of the increased energetic cost of walking in older adults.
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