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Spinal cord injury (SCI) above the lumbosacral level results in lower urinary tract dysfunction, including (1) detrusor hyperreflexia, wherein bladder compliance is low, and (2) a lack of external urethral sphincter (EUS) control, leading to detrusor-sphincter dyssynergia (DSD) with poor voiding efficiency. Experimental studies in animals have shown a dense innervation of serotonergic (5-HT) fibers and multiple 5-HT receptors in the spinal reflex circuits that control voiding function. Here, we investigated the efficacy of NLX-112 (a.k.a. befiradol or F13640), in regulating lower urinary tract function after T8 contusive SCI in rats. NLX-112 is a very potent, highly-selective, and fully efficacious 5-HT(1A) receptor agonist, which has been developed for the treatment of L-DOPA-induced dyskinesia in Parkinson’s disease patients. We performed urodynamics tests and external urethral sphincter electromyogram recordings to assess lower urinary tract function while NLX-112 was infused through the femoral vein in rats with chronic complete SCI or contusive SCI. The dose response studies indicated that NLX-112 was able to improve voiding behavior by regulating both detrusor and EUS activity. These included improvements in voiding efficiency, reduction of detrusor hyperactivity, and phasic activity of EUS during the micturition period. In addition, the application of a selective 5-HT(1A) receptor antagonist, WAY100635, reversed the improved detrusor and EUS activity elicited by NLX-112. In summary, the current data suggest that pharmacological activation of 5-HT(1A) receptors by NLX-112 may constitute a novel therapeutic strategy to treat neurogenic bladder after SCI.

Background: Cellular senescence is a state of stable growth arrest triggered by mitogenic and metabolic stressors. Ageing and a high-fat diet (HFD) are proven inducers of senescence in various organs, presenting a challenge for ageing populations worldwide. Our previous study demonstrated that ROS scavenger N-acetylcysteine (NAC) can improve insulin resistance (IR) and chronic inflammation in diet-induced obesity mice, an effect better achieved through early intervention. We, herein, investigate whether NAC can improve cellular senescence in a diet-induced obesity mouse model, and whether a legacy effect is presented with early intervention. Materials and Methods: For a twelve-month treatment course, all C57B/L6 mice were fed a chow diet (CD), high-fat high-sucrose diet (HFD), CD+NAC1-12 (NAC intervention 1st-12th month), HFD+NAC1-12, and HFD+NAC1-6 (NAC intervention 1st-6th month). Staticalanalysis was used to analyze the different markers of cellular senescence and inflammation. Results: Throughout the study, the HFD group exhibited significantly increased body weight (BW) and body fat, markers of senescence, decreased motor activity (MA) and impaired glucose tolerance. Compared to the HFD group, the HFD+NAC1-12 group exhibited increased MA, decreased BW and body fat, improved glucose tolerance, and decreased senescence markers.The HFD+NAC1-6 group showed similar effects to the HFD+NAC1-12 group, despite discontinuing NAC for 6 months. Our study showed that NAC significantly increased MA in both HFD+NAC1-12 and HFD+NAC1-6 groups, and improved HFD-induced mitochondrial and intracellular ROS expression, DNA and protein oxidative damage, and adipose tissue inflammation. Conclusion: Legacy effect was indeed presented in HFD-induced cellular senescence with NAC intervention, with possible mechanisms being persistently increased motor activity and anti-oxidative stress effects.

Human activity recognition (HAR) has applications to various fields. However, not accounting for the personal differences among various subjects can lead to significant accuracy degradation. To address this problem, we propose a lightweight personalization process that enables an HAR model adapt for various users, some of them ever unseen before. Indeed, by adding a small amount of new labeled data, the model we propose can be personalized and boost the HAR accuracy when dealing with a wide range of target users. Furthermore, we also propose an innovative training algorithm to support personalization during the training stage. Our evaluations on three public real-world datasets demonstrate the superiority of our personalization approach, i.e. 6-14% improvement on the target-domain accuracy, while using only five labeled data points per-class.

Aims: Obesity-induced excessive visceral fat (VF) accumulation is associated with insulin resistance (IR), systemic oxidative stress, and chronic inflammation. As toll-like receptor 4 (TLR4) plays an important role in innate immunity, we herein investigate the effect of TLR4 knockout (T4KO) in a high-fat high-sucrose diet (HFD)-induced obesity mouse model. Results: C57BL6 wild-type (WT) and T4KO mice were fed with either control diet (CD) or HFD for 12 months, rendering four experimental groups: WT+CD, WT+HFD, T4KO+CD, and T4KO+HFD. Compared with WT+CD, WT+HFD demonstrated significant increase in VF accumulation, oxidative damage, M1/M2 macrophage ratio, chronic inflammation, and development of IR. Compared with WT+HFD, T4KO+HFD presented increased BW and body fat with higher subcutaneous fat (SF)/VF ratio, but lower body temperature, as well as decreased oxidative damage, M1/M2 macrophage ratio, chronic inflammation, and IR. Unlike WT+HFD, T4KO+HFD exhibited an increase in mitochondrial electron transport chain activity but a decrease of uncoupling protein 2 (UCP2) level. While T4KO hindered HFD-induced increasing mitochondrial oxygen consumption rate, a shift toward a higher extracellular acidification rate in VF was observed. Notably, T4KO inhibits HFD-induced mitochondrial translocation of nuclear factor of activated T cells 2 (NFATC2), which contributed to mitochondrial metabolic reprogramming. Both fat distribution shifting from VF to SF and mitochondrial metabolic reprogramming may alleviate systemic oxidative stress and chronic inflammation. Innovation and Conclusion: Abrogation of TLR4 contributes to reduction of oxidative stress through metabolic reprogramming of mitochondria in VF, mitigating obesity-induced IR. The study provides critical insight into associating innate immunity-mitochondria interplay with prevention of diabetes.

Non–information technology (IT) professionals and nonexpert casual users are increasingly adopting self-service business intelligence (SSBI) tools (such as Tableau, Qlik, and Power BI) to create data visualization dashboards. This study identified the most relevant dashboard design principles for SSBI tool users. The research approach included organizing a focus group in which most of the participants were non-IT professionals in health care, extracting recommended principles from the literature, applying these recommended principles by using data on quality of diabetes care to design relevant dashboards, and proposing the following 5S dashboard design principle framework: 1) seeing both the forest and trees, 2) simplicity through self-selection, 3) simplicity through significance, 4) simplicity through synthesis, and 5) storytelling. The third and fourth principles are novel and provide solutions to decision-making problems (such as conflicting results from excessive and discordant indicators) encountered by health care professional in the public sector as well as in other domains. The 5S dashboard design principles are easily memorized and practical and thus enable non-IT professionals and nonexpert casual users to design insightful dashboards efficiently by using SSBI tools.

Background. Mitochondrial dynamics (mtDYN) has been proposed as a bridge between mitochondrial dysfunction and insulin resistance (IR), which is involved in the pathogenesis of type 2 diabetes (T2D). Our previous study has identified that mitochondrial DNA (mtDNA) haplogroup B4 is a T2D-susceptible genotype. Using transmitochondrial cybrid model, we have confirmed that haplogroup B4 contributes to cellular IR as well as a profission mtDYN, which can be reversed by antioxidant treatment. However, the causal relationship between mtDYN and cellular IR pertaining to T2D-susceptible haplogroup B4 remains unanswered. Methods. To dissect the mechanisms between mtDYN and IR, knockdown or overexpression of MFN1, MFN2, DRP1, and FIS1 was performed using cybrid B4. We then examined the mitochondrial network and mitochondrial oxidative stress (mtROS) as well as insulin signaling IRS-AKT pathway and glucose transporters (GLUT) translocation to plasma membrane stimulated by insulin. We employed Drp1 inhibitor, mdivi-1, to interfere with endogenous expression of fission to validate the pharmacological effects on IR. Results. Overexpression of MFN1 or MFN2 increased mitochondrial network and reduced mtROS, while knockdown had an opposing effect. In contrast, overexpression of DRP1 or FIS1 decreased mitochondrial network and increased mtROS, while knockdown had an opposing effect. Concomitant with the enhanced mitochondrial network, activation of the IRS1-AKT pathway and GLUT translocation stimulated by insulin were improved. On the contrary, suppression of mitochondrial network caused a reduction of the IRS1-AKT pathway and GLUT translocation stimulated by insulin. Pharmacologically inhibiting mitochondrial fission by the Drp1 inhibitor, mdivi-1, also rescued mitochondrial network, reduced mtROS, and improved insulin signaling of diabetes-susceptible cybrid cells. Conclusion. Our results discovered the causal role of mtDYN proteins in regulating IR resulted from diabetes-susceptible mitochondrial haplogroup. The existence of a bidirectional interaction between mtDYN and mtROS plays an important role. Direct intervention to reverse profission in mtDYN provides a novel therapeutic strategy for IR and T2D.

To improve the clinical outcome of tumor chemotherapy, more effective combination treatments against tumor metastasis and recurrence are required. Licochalcone A (LicA) is the root of Glycyrrhiza inflata and has been reported to possess anti-inflammatory, antimicrobial, and antitumor effects. Sorafenib (Sor), a multikinase inhibitor, is used to treat patients with solid tumors such as advanced hepatocellular carcinoma (HCC). However, the synergistic effects of LicA and Sor on the metastasis of human HCC cells have not been reported. We found that LicA and Sor did not have cytotoxic effects or arrest growth in human SK-Hep-1 and Huh-7 cells. In addition, treatment with LicA or Sor alone inhibited migration and invasion in human SK-Hep-1 and Huh-7 HCC cells. Furthermore, cotreatment with LicA and Sor synergistically inhibited the migration and invasion of HCC cells and significantly inhibited uPA protein expression. Notably, cotreatment of LicA and Sor synergistically and significantly downregulated MKK4-JNK expression. Through tail vein injection in nude mice, the aforementioned cotreatment synergistically suppressed SK-Hep-1 cell-mediated lung metastasis. These findings first revealed the synergistic effects of LicA and Sor cotreatment against human HCC cells, further suggesting that beneficial effects on tumor regression could be confirmed through prospective clinical trials.

This paper demonstrates theoretically that a financial shock can have highly persistent effects on international trade. Motivation is taken from the aftermath of the dramatic trade collapse in 2008–2009, which, despite a substantial recovery, has left a persistently slower growth rate in trade. We find conditions under which a transitory financial shock significantly reduces the investment by firms in entering the export market, and that this can have long-lasting effects on the range of goods exported and hence overall trade. Important to our mechanism are endogenous capital structure decisions by firms in response to the financial shock, and firm entry investment that requires traded goods. This mechanism provides an example of how firm dynamics can serve as a potent propagation mechanism, generating very long-lasting effects of transitory macroeconomic shocks.

Human Ag R (HuR) is an RNA binding protein in the ELAVL protein family. To study the neuron-specific function of HuR, we generated inducible, neuron-specific HuR-deficient mice of both sexes. After tamoxifen-induced deletion of HuR, these mice developed a phenotype consisting of poor balance, decreased movement, and decreased strength. They performed significantly worse on the rotarod test compared with littermate control mice, indicating coordination deficiency. Using the grip-strength test, it was also determined that the forelimbs of neuron-specific HuR-deficient mice were much weaker than littermate control mice. Immunostaining of the brain and cervical spinal cord showed that HuR-deficient neurons had increased levels of cleaved caspase-3, a hallmark of cell apoptosis. Caspase-3 cleavage was especially strong in pyramidal neurons and α motor neurons of HuR-deficient mice. Genome-wide microarray and real-time PCR analysis further indicated that HuR deficiency in neurons resulted in altered expression of genes in the brain involved in cell growth, including trichoplein keratin filament–binding protein, Cdkn2c, G-protein signaling modulator 2, immediate early response 2, superoxide dismutase 1, and Bcl2. The additional enriched Gene Ontology terms in the brain tissues of neuron-specific HuR-deficient mice were largely related to inflammation, including IFN-induced genes and complement components. Importantly, some of these HuR-regulated genes were also significantly altered in the brain and spinal cord of patients with amyotrophic lateral sclerosis. Additionally, neuronal HuR deficiency resulted in the redistribution of TDP43 to cytosolic granules, which has been linked to motor neuron disease. Taken together, we propose that this neuron-specific HuR-deficient mouse strain can potentially be used as a motor neuron disease model.

Solution-processed optoelectronic devices are attractive because of the potential low-cost fabrication and the compatibility with flexible substrate. However, the utilization of toxic elements such as lead and cadmium in current optoelectronic devices on the basis of colloidal quantum dots raises environmental concerns. Here we demonstrate that white-light-emitting diodes can be achieved by utilizing non-toxic and environment-friendly gold nanoclusters. Yellow-light-emitting gold nanoclusters were synthesized and capped with trioctylphosphine. These gold nanoclusters were then blended with the blue-light-emitting organic host materials to form the emissive layer. A current efficiency of 0.13 cd/A was achieved. The Commission Internationale de l’Eclairage chromaticity coordinates of (0.27, 0.33) were obtained from our experimental analysis, which is quite close to the ideal pure white emission coordinates (0.33, 0.33). Potential applications include innovative lighting devices and monitor backlight.

Previous studies reported that norcantharidin (NCTD) has anti-tumor effects. We investigated the antitumor effects and underlying mechanism of NCTD on human renal cancer in vitro and in vivo. NCTD significantly decreased renal cancer cell viability by induction of apoptosis, as determined by the MTT assay and annexin V/PI staining. NCTD treatment of 786-O and A-498 cells altered the expression of caspase family proteins and PARP. Moreover, NCTD induced mitochondrial depolarization, which was accompanied by an increased level of Bax and decreased levels of Bcl-2 and Mcl-1. NCTD induced endoplasmic reticulum (ER) stress by increasing the expression of Grp78, p-elF2α, ATF4, and CHOP. Pretreatment with an ER stress inhibitor (salubrinal) significantly attenuated the effect of NCTD. NCTD also induced activation of the AKT pathway in 786-O and A-498 cells. Overexpression of AKT partly reversed the effect of NCTD on apoptosis. NCTD treatment led to decreased expression of Bcl-2 and Mcl-1, and increased expression of Bax, cleaved-caspase-9, cleaved-PARP, and p-elF2α. Our in vivo studies demonstrated that NCTD significantly inhibited tumor growth in a nude mouse xenograft model. Taken together, our results suggest that NCTD is a potential anti-tumor agent for treatment of renal carcinoma.

Financial frictions can pose a barrier to export entry by altering a firm's long-term capital structure. The focus on long-term firm financing is motivated by our empirical finding that exporting firms tend to be more leveraged than non-exporting firms in terms of long-term debt, as distinct from short-term working capital. We explain this fact by marrying a corporate finance model of capital structure, featuring an endogenous choice between equity and long-term debt, with a trade model featuring heterogeneous firms and export entry. The model predicts that exporting firms will prioritize reducing the cost of long-term capital over relaxing a short-term working capital constraint to scale up production.

This paper proposes a neural fuzzy evaluation system (NFES) with significant variables selected from stepwise regression to predict apnea-hypopnea index (AHI) for evaluating obstructive sleep apnea (OSA). The variables considered are the change statuses of blood pressure (BP) before going to sleep and early in the morning as well as other five easily available measurements (age, body mass index (BMI), etc.) so that users can use the system for self-evaluation of OSA. A total of 150 subjects are reviewed retrospectively and categorized as training (120 subjects) and validation (30 subjects) sets by a fivefold cross-validation scheme with stratified sampling based on the OSA severity. Among the eight variables, the stepwise regression shows that BMI, the difference of systolic BP, and Epworth Sleepiness Scale were the significant factors to predict AHI. The three variables are fed as inputs to the NFES with interpretable fuzzy rules automatically generated from the training set. The average accuracy, sensitivity (Sn), specificity (Sp), and Sn+Sp-1 of the NFES were 75.6%, 77.2%, 75.0%, and 0.552, respectively, in distinguishing the OSA level of normal-mild (AHI

Eight weeks post contusive spinal cord injury, we built a peripheral nerve graft bridge (PNG) through the cystic cavity and treated the graft/host interface with acidic fibroblast growth factor (aFGF) and chondroitinase ABC (ChABC). This combinatorial strategy remarkably enhanced integration between host astrocytes and graft Schwann cells, allowing for robust growth, especially of catecholaminergic axons, through the graft and back into the distal spinal cord. In the absence of aFGF+ChABC fewer catecholaminergic axons entered the graft, no axons exited, and Schwann cells and astrocytes failed to integrate. In sharp contrast with the acutely bridge-repaired cord, in the chronically repaired cord only low levels of serotonergic axons regenerated into the graft, with no evidence of re-entry back into the spinal cord. The failure of axons to regenerate was strongly correlated with a dramatic increase of SOCS3 expression. While regeneration was more limited overall than at acute stages, our combinatorial strategy in the chronically injured animals prevented a decline in locomotor behavior and bladder physiology outcomes associated with an invasive repair strategy. These results indicate that PNG+aFGF+ChABC treatment of the chronically contused spinal cord can provide a permissive substrate for the regeneration of certain neuronal populations that retain a growth potential over time, and lead to functional improvements.

This article shows that firm entry dynamics are an important part of the propagation of financial shocks to the real macroeconomy. A VAR documents empirically that adverse financial shocks are associated with significant declines in both new firm creation and equity values. A DSGE business cycle model combining endogenous firm entry and financial frictions, where firms have a choice of financing entry through debt or equity, can explain these facts. The model implies that adjustment in firm numbers can moderate the impact of financial shocks on aggregate output, as it buffers the equity value and financial stance of surviving firms.

Background/Purpose Improvement of the medical and social environment is an important aspect of government policies in assuring the quality of life (QoL) of older adults. However, few studies have appraised the impact and relationship of QoL with clinical factors among elderly individuals in affluent residential areas. Methods A total of 166 older adults from Chang Gung Health and Culture Village were enrolled. Oral health-related QoL was measured using the Geriatric Oral Health Assessment Index. Self-assessed chewing abilities and demographic characteristics were collected by questionnaire. Physical health was scored by activities of daily living (ADL) and instrumental ADL. Mini nutrition assessment questionnaire was used to evaluate the nutritional intake. Multiple linear regression was used to predict risk factors affecting QoL and to examine whether chewing ability was a mediator of oral health-related QoL. Results Poor chewing ability was associated with older age (OR = 1.82 for 76–85 years and 3.58 for 86–95 years), sufficient economic status (OR = 5.55) and removable denture-wearing (OR = 7.52). On the other hand, poor chewing ability (OR = 0.11), removable denture-wearing (OR = 0.48), periodontal disease (OR = 0.38) had lower likelihood of good oral health-related QoL. Mediator analyses showed that chewing ability was a mediator for the association between oral health-related QoL and economic status or removable denture-wearing or having more than 20 teeth. Periodontal disease was an independent factor for oral health-related QoL. Conclusion Among older adults in an affluent community, periodontal disease is an independent risk factor directly related to oral health-related QoL, whereas chewing ability is a mediator between QoL and removable denture-wearing.

A defining feature of chordates is the unique presence of a dorsal hollow neural tube that forms by internalization of the ectodermal neural plate specified via inhibition of BMP signaling during gastrulation. While BMP controls dorsoventral (DV) patterning across diverse bilaterians, the BMP-active side is ventral in chordates and dorsal in many other bilaterians. How this phylum-specific DV inversion occurs and whether it is coupled to the emergence of the dorsal neural plate are unknown. Here we explore these questions by investigating an indirect-developing enteropneust from the hemichordate phylum, which together with echinoderms form a sister group of the chordates. We found that in the hemichordate larva, BMP signaling is required for DV patterning and is sufficient to repress neurogenesis. We also found that transient overactivation of BMP signaling during gastrulation concomitantly blocked mouth formation and centralized the nervous system to the ventral ectoderm in both hemichordate and sea urchin larvae. Moreover, this mouthless, neurogenic ventral ectoderm displayed a medial-to-lateral organization similar to that of the chordate neural plate. Thus, indirect-developing deuterostomes use BMP signaling in DV and neural patterning, and an elevated BMP level during gastrulation drives pronounced morphological changes reminiscent of a DV inversion. These findings provide a mechanistic basis to support the hypothesis that an inverse chordate body plan emerged from an indirect-developing ancestor by tinkering with BMP signaling.

Solution-processed optoelectronic devices are attractive because of the potential low-cost fabrication and the compatibility with flexible substrate. However, the utilization of toxic elements such as lead and cadmium in current optoelectronic devices on the basis of colloidal quantum dots raises environmental concerns. Here we demonstrate that white-light-emitting diodes can be achieved by utilizing non-toxic and environment-friendly gold nanoclusters. Yellow-light-emitting gold nanoclusters were synthesized and capped with trioctylphosphine. These gold nanoclusters were then blended with the blue-light-emitting organic host materials to form the emissive layer. A current efficiency of 0.13 cd/A was achieved. The Commission Internationale de l'Eclairage chromaticity coordinates of (0.27, 0.33) were obtained from our experimental analysis, which is quite close to the ideal pure white emission coordinates (0.33, 0.33). Potential applications include innovative lighting devices and monitor backlight.

Model compression has emerged as an important area of research for deploying deep learning models on Internet-of-Things (IoT). However, for extremely memory-constrained scenarios, even the compressed models cannot fit within the memory of a single device and, as a result, must be distributed across multiple devices. This leads to a distributed inference paradigm in which memory and communication costs represent a major bottleneck. Yet, existing model compression techniques are not communication-aware. Therefore, we propose Network of Neural Networks (NoNN), a new distributed IoT learning paradigm that compresses a large pretrained 'teacher' deep network into several disjoint and highly-compressed 'student' modules, without loss of accuracy. Moreover, we propose a network science-based knowledge partitioning algorithm for the teacher model, and then train individual students on the resulting disjoint partitions. Extensive experimentation on five image classification datasets, for user-defined memory/performance budgets, show that NoNN achieves higher accuracy than several baselines and similar accuracy as the teacher model, while using minimal communication among students. Finally, as a case study, we deploy the proposed model for CIFAR-10 dataset on edge devices and demonstrate significant improvements in memory footprint (up to 24x), performance (up to 12x), and energy per node (up to 14x) compared to the large teacher model. We further show that for distributed inference on multiple edge devices, our proposed NoNN model results in up to 33x reduction in total latency w.r.t. a state-of-the-art model compression baseline., Comment: This preprint is for personal use only. The official article will appear as part of the ESWEEK-TECS special issue and will be presented in the International Conference on Hardware/Software Codesign and System Synthesis (CODES+ISSS), 2019

This paper develops an inter-temporal current account model to study the impacts of expected rising housing prices on trade surpluses in China. The model shows two channels working in opposite directions. The first channel is the intra-temporal substitution channel. It discourages current consumption of tradable goods, leading to trade surpluses. The second is the inter-temporal substitution channel, which instead leads to trade deficits. When intra-temporal channel dominates, expected rising housing prices lead to trade surpluses. However, borrowing constraints on housing purchases may weaken the intra-temporal substitution channel and thus weaken the positive correlation between expected housing prices and trade surpluses. We show empirically that expected rising housing prices lead to trade surpluses in China. We also identify possible reason for this finding: strong intra-temporal substitution elasticity due to large male to female sex ratio in China. We further show that the positive relation between expected rising housing prices and trade surpluses is weaker in regions with more stringent borrowing constraints, consistent with our model’s prediction.

This article analyzes the impacts of foreign direct investment (FDI) and short-term capital flows, otherwise known as hot money, on stock and house prices in China. Empirical results, estimated using the local projections approach, reveal that a positive hot money net inflow shock significantly increases stock and house prices and the impacts persist for up to 1–2 months, while a positive FDI net inflow shock contributes significantly to lagged house price appreciation but has no effect on stock prices. This study also identifies negative pass-through effects of FDI net inflows on hot money net inflows and positive pass-through effects of stock prices on house prices.

The purpose of the study was to discuss the relationship among leisure experience, perceived value and behavioral intentions for the tourists in Xitou Monster Village, Taiwan. 260 copies of questionnaire were distributed and 247 copies were effective. The data was analyzed by using descriptive statistics analysis, exploratory factor analysis, reliability analysis, validity analysis and linear structural equation modeling. The results were as follows: 1. The tourists background are mostly: female, 21~30 years old, living in the north, graduated from universities, monthly income under NT$20,000, traveling with relatives, driving by self and introduced from friends; 2. The result of path analysis indicated that leisure experience had a significant impact on perceived value; leisure experience had a positive effect on behavioral intentions; perceived value would positive affect on behavioral intentions. According to the result, suggestions and managerial implication also recommended.

Studies suggest that self-affirmation interventions may help increase students' tendencies to confront challenges. However, we posited that self-affirmation cannot help students with higher levels of fear of being laughed at (gelotophobia) confront challenges because it may lead them to accept negative information (feelings of threat) about their ability and decrease their perceptions of self-ability. In support of this hypothesis, Experiment 1 found that being attribute-affirmed enhanced the tendencies to confront a challenging task for junior high school students with low gelotophobia, but not for those with high gelotophobia. Experiment 2 revealed that being value-affirmed increased challenge-confronting tendencies for senior high school students with low gelotophobia. However, it decreased high gelotophobia students' challenge-confronting tendencies because it caused them to feel less capable of performing the task. Thus, self-affirmation, which may decrease high gelotophobia students' self-perceived ability in challenging situations, may be unhelpful or even harmful in motivating them to confront challenges.

The indirect-developing enteropneust acorn worm Ptychodera flava has been used as a hemichordate model system for studying the developmental evolution of deuterostome body plans and the origins of chordate characteristics. However, research progress has been hindered by the limited accessibility of its embryonic materials and metamorphosing larvae. In this study, we identified an abundant population of P. flava in Penghu, Taiwan, and examined the feasibility of using this animal for developmental studies. Through histological examination, we established that the reproductive season of this population is between September and December, with a peak breeding period in October and November. In addition, we have developed new procedures that can induce P. flava spawning at any time of the day during the breeding season, with a higher successful rate than that achieved using a previously published method. Moreover, the culturing system we developed enables rearing of P. flava larvae through various planktonic stages and eventual metamorphosis into benthic juveniles, all under laboratory conditions. We anticipate that the animal resources and new technical procedures reported here will further facilitate the use of P. flava as a model organism for evolutionary and developmental biology research.

The two aims of this study were (1) designing and developing an affordable visual reaction system for badminton training that monitors and provides instant feedback on agility; and (2) to measure and improve the footwork and movement of badminton players and output useful reference data. Ten junior high school badminton players were invited to serve as the subjects of this study. They participated in a three-week (nine sessions) training program. Training was primarily in the form of fixed or random footwork drills. Timed tests were performed before and after each session to measure the players’ agility in performing six-point and four-point footwork drills. The results were compared to the training effects calculated using dependent-sample t-tests. In addition, the long-term durability and functionality of the training system were tested. The training system was able to maintain stable and reliable training and evaluation operations for extended periods. Results showed significant improvements in the visual reaction time (p = 0.003) and agility (p = 0.001) of players. The proposed training system is an affordable option for training and monitoring, evaluating, and recording training performance. It can accurately record movement and response times and simulate competitive environments.

Spinal cord injury (SCI) above the lumbosacral level results in lower urinary tract dysfunction, including (1) detrusor hyperreflexia, wherein bladder compliance is low, and (2) a lack of external urethral sphincter (EUS) control, leading to detrusor-sphincter dyssynergia (DSD) with poor voiding efficiency. Experimental studies in animals have shown a dense innervation of serotonergic (5-HT) fibers and multiple 5-HT receptors in the spinal reflex circuits that control voiding function. Here, we investigated the efficacy of NLX-112 (a.k.a. befiradol or F13640), in regulating lower urinary tract function after T8 contusive SCI in rats. NLX-112 is a very potent, highly-selective, and fully efficacious 5-HT1A receptor agonist, which has been developed for the treatment of L-DOPA-induced dyskinesia in Parkinson's disease patients. We performed urodynamics tests and external urethral sphincter electromyogram recordings to assess lower urinary tract function while NLX-112 was infused through the femoral vein in rats with chronic complete SCI or contusive SCI. The dose response studies indicated that NLX-112 was able to improve voiding behavior by regulating both detrusor and EUS activity. These included improvements in voiding efficiency, reduction of detrusor hyperactivity, and phasic activity of EUS during the micturition period. In addition, the application of a selective 5-HT1A receptor antagonist, WAY100635, reversed the improved detrusor and EUS activity elicited by NLX-112. In summary, the current data suggest that pharmacological activation of 5-HT1A receptors by NLX-112 may constitute a novel therapeutic strategy to treat neurogenic bladder after SCI.

Spinal cord injury (SCI) causes impaired neuronal function with associated deficits in the musculoskeletal system, which can lead to permanent disability. Here, the impact of SCI on in vivo musculoskeletal adaptation was determined by studying deficits in locomotor function and analyzing changes that occur in the muscle and bone compartments within the rat hindlimb after contusion or transection SCI. Analyses of locomotor patterns, as assessed via the Basso, Beattie, and Bresnahan (BBB) rating scale, revealed that transection animals showed significant deficits, while the contusion group had moderate deficits, compared with naive groups. Muscle myofiber cross-sectional areas (CSA) of both the soleus and tibialis anterior muscles were significantly decreased three months after contusion SCI. Such decreases in CSA were even more dramatic in the transection SCI group, suggesting a dependence on muscle activity, which is further validated by the correlation analyses between BBB score and myofiber CSA. Bone compartment analyses, however, revealed that transection animals showed the most significant deficits, while contusion animals showed no significant differences in the trabecular bone content within the proximal tibia compartment. In general, values of bone volume per total bone volume (BV/TV) were similar across the SCI groups. Significant decreases were observed, however, in the transection animals for bone mineral content, bone mineral density, and three-dimensional trabecular structure parameters (trabecular number, thickness, and spacing) compared with the naive and contusion groups. Together, these findings suggest an altered musculoskeletal system can be correlated directly to motor dysfunctions seen after SCI.

Human antigen R (HuR), is an RNA binding protein in the human antigen protein family. To study the neuron-specific function of HuR, we generated inducible, neuron-specific HuR-deficient mice of both sexes. After tamoxifen-induced deletion of HuR, these mice developed a phenotype consisting of poor balance, decreased movement, and decreased strength. They performed significantly worse on the rotarod test compared to littermate control mice, indicating coordination deficiency. Using the grip strength test, it was also determined that the forelimbs of neuron-specific HuR-deficient mice were much weaker than littermate control mice. Immunostaining of the brain and cervical spinal cord showed that HuR-deficient neurons had increased levels of cleaved Caspase 3, a hallmark of cell apoptosis. Caspase 3 cleavage was especially strong in pyramidal neurons and alpha motor neurons of HuR-deficient mice. Genome-wide microarray and RT-PCR analysis further indicated that HuR deficiency in neurons resulted in altered expression of genes in the brain involved in cell growth, including Tchp, Cdkn2c, GPSM2, Ier2, SOD1, and Bcl2. The additional enriched GO terms in the brain tissues of neuron-specific HuR-deficient mice were largely related to inflammation, including interferon-induced genes and complement components. Importantly, some of these HuR-regulated genes were also significantly altered in the brain and spinal cord of patients with amyotrophic lateral sclerosis. Additionally, neuronal HuR deficiency resulted in the redistribution of TDP43 to cytosolic granules, which has been linked to motor neuron disease. Taken together, we propose that this neuron-specific HuR-deficient mouse strain can potentially be used as a motor neuron disease model.

The purpose of this case report was to introduce a novel technique for de-epithelializing autogenous gingival graft that can be combined with coronally advanced flap for root coverage and soft tissue augmentation. This technique allows for easier, predictable harvesting of connective tissue of excellent quality and quantity without inclusion of undesirable submucosa or adipose tissues. Reduced surgical chair time and double protection of the donor site using the combination of cyanoacrylate and periodontal dressing allowed for uneventful postoperative healing.

Reactive oxygen species (ROS) plays a crucial role in pathogenesis of insulin resistance (IR) and type 2 diabetes. In the United Kingdom, Prospective Diabetes Study and its 10-year post-trial monitoring, a beneficial effect of early optimisation of blood glucose control is clearly demonstrated. In this study, we investigated whether ROS scavenger N-acetylcysteine (NAC) and the time point of intervention can affect IR in a diet-induced obesity mouse model. Male C57B/L6 mice were fed chow diet (CD), high-fat high-sucrose diet (HFD), CD + NAC1-6 (NAC intervention 1st to 6th month), HFD + NAC1-6, and HFD + NAC3-6 (NAC intervention 3rd to 6th month) for a 6-month treatment course. HFD group showed significantly increased body weight (BW) and body fat, decreased motor activity (MA), impaired intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (IPITT) throughout the study. HFD + NAC1-6, as compared with HFD group, had increased MA, improved IPGTT and IPITT since first month, followed by decreased BW and body fat. HFD + NAC3-6 group, although showed improved IPGTT and IPITT than HFD group, still had higher BW, decreased MA, and impaired IPGTT and IPITT as compared with HFD + NAC1-6 at the end of the study. NAC significantly increased MA, and ameliorated the HFD-induced mitochondrial and intracellular ROS expression, DNA and protein oxidative damage, and adipose tissue inflammation. We concluded that ROS scavenger can improve IR and chronic inflammation in diet-induced obesity mice. This action is likely better expressed through early intervention. The mechanism is probably through a virtuous circle of suppressed oxidative stress, and increased motor activity, which helps to reduce body fat.

Praeruptorin A (PA) is a pyranocumarin present in the dried root of Peucedanumpraeruptorum Dunn that has anticancer effects against several types of cells. However, the effect of PA on human cervical cancer cells is unknown. Our results indicate that PA significantly inhibited cell proliferation, colony formation, migration, invasion, and wound closure of HeLa and SiHa cells, induced cell cycle arrest at G0/G1 phase, upregulated Rb, p16, p21 and p27 proteins and downregulated cyclin D1 and S-phase kinase-associated protein 2 (Skp2) proteins. PA also significantly reduced expression of matrix metalloproteinase-2 (MMP-2) and increased expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). In addition, PA suppressed ERK1/2 activation and increased the effect of PD98059 (a specific MEK1/2 inhibitor) in downregulation of MMP-2 and upregulation of TIMP-2. PA treatment inhibited the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on upregulation of ERK1/2 activation, MMP-2 expression, cellular migration, and invasion of HeLa cells. Our findings are the first to demonstrate the activity of PA against cervical cancer cells, and suggest this agent has promise as a therapeutic agent in treatment of human cervical cancer.

A preclinical trial was conducted to treat 54 mandibular critical-sized alveolar ridge defects in 27 canines. Each hemimandible was randomized to be treated with two different anorganic bovine bone grafts (group A = InterOss [SigmaGraft]; group B = Bio-Oss [Geistlich]) or negative control (group C = empty defect) followed by a 4-, 8-, or 12-week observation period. Microcomputed tomography, histology, histopathology, and histomorphometric analyses were performed to evaluate the safety and efficacy of these treatments. By all the parameters assessed in this study, the biocompatibility and healing of group A treated defects were indistinguishable from those in group B. Radiographic comparison of graft resorption and bony integration demonstrated similar mean scores for both treatment groups. Likewise, no statistical differences were observed between the two groups with respect to percent mineralized volume and density. When compared to the critical-sized empty controls, both treatment groups showed statistically greater amounts of bone present in the defect sites and appeared to help preserve the mesial and distal alveolar walls of the defect. Histomorphometry also supported the similarity in performance of both tested groups as no statistically significant differences were observed with regard to percent bone, percent residual implant, and percent bone marrow values. While not statistically different, on average group A had more than twice the mean amount of bone present at 8 and 12 weeks compared to group B. Overall, group A had a good biocompatibility response, similar to group B. Clinical studies are recommended to confirm these findings.

The understanding of the pain frequency of patients can facilitate medical professional diagnosis, so self-management tools for pain have gained increasing attention. However, there have been just a limited number of tools for children who are not highly literate. In this study, the first of 10 children aged from 3 to 9 as objects, to clarify the extent of the children's understanding of graphic design elements. With 96 children aged from 4 to 9 as the research subjects, this study explores children's understanding of the graphs of pain frequency. The results are adopted for the development of the pain management tools for children.

The present study investigates the endogenous expression of Suppressor of Cytokine Signaling-3 (SOCS3) after spinal cord injury (SCI) and its effect on SCI-induced cell death in vivo. In addition, we determined whether a reduction of SOCS3 expression induced by microinjection of short hairpin RNA (shSOCS3) carried by lentivirus into spinal cord provides cellular protection after SCI. We demonstrated that complete transection of rat T8 spinal cord induced SOCS3 expression at the mRNA and protein levels as early as 2 days post-injury, which was maintained up to 14 days. SOCS3 immunoreactivity was detected in neurons and activated microglia after SCI. We also demonstrated that SCI induces phosphorylation of proteins that are involved in signal transduction and transcription-3 (STAT3) in neurons, which induced SOCS3 expression. Western blot analyses and double-immunofluorescent staining showed significant up-regulation of the pro-apoptotic protein Bax, increases in the ratio of Bax to the anti-apoptotic protein Bcl-2, and up-regulation of cleaved caspase-3 in neurons. Treatment with shSOCS3 inhibited SCI-induced mRNA expression of SOCS3 2 days post-injury and suppressed SCI-induced Bax expression 7 days after SCI, both rostral and caudal to the lesion. Moreover, treatment with shSOCS3 inhibited SCI-induced neuronal death and protected neuronal morphology both rostral and caudal to the injury site 7 days post-injury. Our results suggest that the STAT3/SOCS3 signaling pathway plays an important role in regulating neuronal death after SCI.

Symbiotic copepods compose one-third of the known copepod species and are associated with a wide range of animal groups. Two parasitic copepods endoparasitic in acorn worms (Hemichordata), Ive balanoglossi and Ubius hilli, collected in the Mediterranean Sea and Australian waters, respectively, were described a century ago. Here we report a new parasitic copepod species, Ive ptychoderae sp. nov., found in Ptychodera flava, a widespread acorn worm in the Indo-Pacific Ocean and an emerging organism for developmental and evolutionary studies. The female of I. ptychoderae is characterized by having a reduced maxilliped and five pairs of annular swellings along the body that are morphologically similar but distinguishable from those in the two previously described parasitic copepods in acorn worms. Phylogenetic analysis based on the 18S rDNA sequence shows that I. ptychoderae may belong to Poecilostomatoida but represent a new family, which we name Iveidae fam. nov. Ive ptychoderae is commonly found in the acorn worm population with an average prevalence of 42% during the collecting period. The infection of the parasite induces the formation of cysts and causes localized lesions of the host tissues, suggesting that it may have negative effects on its host. Interestingly, most cysts contain a single female with one or multiple male copepods, suggesting that their sex determination may be controlled by environmental conditions. The relationships between the parasitic copepods and acorn worms thus provide a platform for understanding physiological and ecological influences and coevolution between parasites and hosts.

Thermal ground planes (TGPs) are passive thermal management devices that utilize the phase-change of a working fluid to achieve high thermal conductivity and low thermal resistance. TGPs are flat, two-dimensional heat pipes—similar to vapor chambers—in which liquid is held within a capillary wick, and vapor is held in a sealed vapor layer. Heat is absorbed at an evaporator region, causing the liquid to evaporate. The heated vapor in the vapor core is carried via convection to a condenser region where it condenses as the heat is expelled from the TGP to an external heat sink. The condensed liquid is then pulled back to the evaporator via capillary forces in the wick. In numerous applications, mechanical flexibility of the TGP is required, as is low-cost manufacturing and viable integration routes with electronics. This work describes a flexible TGP (FTGP) fabricated using printed circuit board (PCB) technology, in which commercially available copper-cladded polyimide sheets are used as the casing material. The wick is composed of three layers of fine copper mesh electroplated or sintered together and coated with atomic layer deposited TiO2. A coarse nylon or polyether ether ketone (PEEK) mesh defines the vapor transport layer, and water is used as the working fluid. The perimeter of the device is heat-sealed with flouroethylene propylene (FEP), which has been found to provide a near-hermetic seal for several months and is suitable for flexible applications. This architecture allows the TGP to function with minimal reduction in heat transfer performance while bent by 90 deg, and full functionality is returned when the device is returned to its flat configuration. The FTGP's measured thermal resistance is about half that of an equivalent copper reference for input heat fluxes of 3–6 W/cm2. More than 30 copper-cladded polyimide FTGPs were fabricated and characterized using both simple qualitative and more involved quantitative test setups. The results show that the fabrication and assembly processes developed in this work are repeatable and the devices are durable.

Previous studies have demonstrated that endorsing an incremental theory of intelligence is helpful in motivating students to confront challenges. We used a survey to examine whether this theory could predict greater challenge-confronting tendencies for students with relatively high gelotophobia (i.e., the fear of being laughed at) and explore the possible underlying processes. A total of 264 senior high school students completed the measures of gelotophobia, implicit theories of intelligence, challenge-confronting tendencies, perceived value and feelings of being threatened in confronting challenges, and their self-perceived general ability. The results showed that endorsing an incremental theory predicted greater perceived value in confronting challenges and stronger challenge-confronting tendencies for students with relatively low gelotophobia. However, for those with relatively high gelotophobia, although this theory also predicted greater perceived value in confronting challenges, it was unrelated to challenge-confronting tendencies. Thus, endorsing an incremental theory is helpful but insufficient in motivating high gelotophobia students to exhibit stronger challenge-confronting tendencies.

This study investigated whether animals sustaining experimental damage to the basal forebrain cholinergic system would benefit from treatment with exogenous neurotrophic factors. Specifically, we set out to determine whether neurotrophic factors would rescue damaged cholinergic neurons and improve behavioral performance on a spatial learning and memory task. Adult rats received bilateral injections of either saline (controls) or 192 IgG-saporin to damage basal forebrain cholinergic neurons (BFCNs). Two weeks later, animals received implants of an Alzet mini-pump connected to cannulae implanted bilaterally in the lateral ventricles. Animals received infusions of nerve growth factor (NGF), neurotrophin 3 (NT3), a combination of NGF and NT3, or a saline control over a 4-week period. Compared to saline-treated controls, animals sustaining saporin-induced damage to BFCNs took significantly more trials to learn a delayed match to position task and also performed more poorly on subsequent tests, with increasing delays between test runs. In contrast, animals infused with neurotrophins after saporin treatment performed significantly better than animals receiving saline infusions; no differences were detected for performance scores among animals infused with NGF, NT3, or a combination of NGF and NT3. Studies of ChAT immunnocytochemical labeling of BFCNs revealed a reduction in the numbers of ChAT-positive neurons in septum, nucleus of diagonal band, and nucleus basalis in animals treated with saporin followed by saline infusions, whereas animals treated with infusions of NGF, NT3 or a combination of NGF and NT3 showed only modest reductions in ChAT-positive neurons. Together, these data support the notion that administration of neurotrophic factors can rescue basal forebrain cholinergic neurons and improve learning and memory performance in rats. © 2013 Elsevier Inc.

The trend of medical career choice in the younger generation has resulted in deficiency of manpower in the four major disciplines of internal medicine, surgery, obstetrics/gynecology, and pediatrics, which will threaten people's health care in Taiwan. However, perceptions of gender awareness and factors affecting the career choices of medical students have not been investigated systemically in Taiwan. To explore the perceptions on gender awareness and considerations in career choices, we recruited 280 1(st)- and 7(th)-year male and female medical students at a Medical University for the study. A modified Nijmegen questionnaire using a 5-point Likert scale containing medical curricula (18 items), gender awareness (13 items), and career inclination (9 items) was adopted as the investigation tool in our study. The response rate was 75% (224/280). With regard to gender, the 1(st)-year male students had greater confidence in being a physician than the female students (p

Megadose of vitamin C (MVC) has been proposed for an emergent treatment of acute paraquat (PQ) poisoning. However, the safety issue of this treatment protocol has not been evaluated. Here, we present the first evidence that vitamin C can promote aggravated production of hydroxyl radical (OH(•)) via interacting with preexisting PQ(+•)/H2O2 system in a nonmetal-catalyzed manner. This enhanced oxidative stress would therefore expect to cause more deleterious effect during acute PQ intoxication. To lend support to this possibility, we set out to attest the effects of MVC on a simulated, PQ-intoxicated, Madin-Darby canine kidney (MDCK) cell model. First, PQ alone could trigger oxidative-nitrosative stress (ONS) through robust generation of reactive oxygen species and nitric oxide (NO) that could induce apoptotic killing via promoting effective release of mitochondrial cytochrome c, an apoptogenic factor. The percentage of apoptosis for MDCK cells treated with 1.0 mM PQ for 24 h was 16.3 ± 13.0%. However, when MDCK cells were treated with a combination of PQ (1.0 mM) and MVC (20 mM) for 24 h, the severity of apoptotic killing was further exacerbated as reflected by a nearly 7-fold increase in the release of mitochondrial cytochrome c and the percentage of apoptotic cell population rose sharply to 90.7 ± 5.1%. These data indicate that MVC apparently exacerbates further killing rather than cytoprotection on this simulated, PQ-intoxicated MDCK cell model and suggest that the treatment of PQ poisoning using MVC protocol should be cautious.