A key objective of studying biological systems is to design therapeutic intervention strategies for beneficially altering cell dynamics. Derivation of control policies is hindered by the high-dimensional state spaces associated with gene regulatory networks. Hence, it is critical to reduce the network complexity and the paper aims to address this issue by focusing on the distribution of the canalizing power (CP) of the genes in the model. Canalizing genes enforce broad corrective actions on cellular processes and play a crucial role in producing optimal reactions to external stimuli. Therefore, it is critical to reduce the network while preserving the canalizing power of genes. We reduce Boolean networks with perturbation by removing genes with the smallest canalizing power consecutively, and evaluate the stability of canalizing power. A systematic empirical study demonstrates that there are two classes of networks, reducible and irreducible with respect to the preservation of canalizing power of the genes. Based on these observations, we introduce the definition of reducible networks and proceed with the problem of selecting the relevant network features that allow for discriminating networks from the two different classes. We demonstrate the efficacy of the selected features on synthetic and real gene regulatory networks.

Objectives: Reduced glucose utilization in the main parts of the brain involved in memory is a major cause of Alzheimer’s disease, in which ketone bodies are used as the only and effective alternative energy source of glucose. This study examined the effects of a low-carbohydrate and high-fat (LCHF) diet supplemented with a ketogenic nutrition drink on cognitive function and physical activity in the elderly at high risk for dementia.

BACKGROUND:Sugammadex is a reversal agent for non-depolarizing neuromuscular blockers and widely used worldwide on account of its rapid and effective reversal from neuromuscular blockade, despite its advantages, multiple cases of sugammadex-induced anaphylactic shock have been reported.CASE:A 42-year-old man developed anaphylactic shock in the postanesthesia care unit. Initially, sugammadex was suspected as the causative agent, but an intradermal skin test revealed negative results. A further skin test was performed with sugammadex-rocuronium complex that yielded positive results.CONCLUSIONS:Anesthesiologists and healthcare providers should be aware of the possibility of anaphylaxis from the sugammadex-rocuronium complex, as well as from sugammadex or rocuronium alone.

Genomic regulatory networks are examples of complex systems with distributed control and abundant feedback. The concept of genes that can constrain, or canalize, such a complex network to a specic behavior was first proposed by C. Waddington in 1942 [1]. Waddington stipulated the existence of genes that can produce reliable developmental effects against genetic mutations or environmental changes during evolution [2], [1]. Zhao et al. [3] made a clear distinction between master genes and canalizing genes. Both master and canalizing genes exert a strong control over many downstream gene pathways; however, canalizing genes have an additional ability of taking over the control and overriding other regulatory instructions. Canalizing genes produce adaptive and optimal reactions to environmental, stochastic and genetic perturbations and they are essential in a complex system, so it can achieve biological robustness and buffer itself from the eects of random alterations or operating errors. Our work suggests that the currently adopted denitions of canalizing and master genes should be modified to include a relative characterization of these properties in such a way that a particular gene does not have to be exclusively a master or a canalizing one.

MOTIVATION:Canalizing genes enforce broad corrective actions on cellular processes for the purpose of biological robustness maintaining a constant phenotype to remain unchanged in spite of genetic mutations or environmental perturbations. Despite their central role in biological systems, the observation/detection of canalizing genes is often impeded because the behavior of affected genes is highly varied relative to the inactive canalizer. Therefore, the activity of canalizing genes is difficult to predict to any significant degree by their subject genes under normal cell conditions. RESULTS:We investigate this question and present a quantitative framework that allows for the estimation of the power of canalizing genes in the context of Boolean Networks (BNs) with perturbation. This framework borrows tools from the Pattern Recognition theory and uses the coefficient of determination (CoD) to capture the capacity of the canalizing genes. The canalizing power (CP) of a gene is quantitatively characterized by two terms: regulation power (RP) and incapacitating power (IP). We base this assumption on the idea that canalizing power of a gene should be quantified by the extent of its regulation on the overall network and the extent of control that the gene takes over from other master genes when it is activated, which is equivalent to reduction of the control of other master genes upon its activation. Following this, the CP concept is illustrated with examples in which the goal is to provide preliminary evidence that CP can be used to characterize the ability of canalizing genes. AVAILABILITY AND IMPLEMENTATION:A library of functions written in MATLAB for computing CP is available at http://github.com/eunjikim-angie/CanalizingPower.

BACKGROUND Microbial metabolism of lignans from high-fiber plant foods produces bioactive enterolignans, such as enterolactone (ENL) and enterodiol (END). Enterolignan exposure influences cellular pathways important to cancer risk and is associated with reduced colon tumorigenesis in animal models and lower colorectal cancer risk in humans. OBJECTIVES The aim of this study was to test the effects of a flaxseed lignan supplement (50 mg secoisolariciresinol diglucoside/d) compared with placebo on host gene expression in colon biopsies and exfoliated colonocyte RNA in feces and fecal microbial community composition, and to compare responses in relation to ENL excretion. METHODS We conducted a 2-period randomized, crossover intervention in 42 healthy men and women (20-45 y). We used RNA-seq to measure differentially expressed (DE) genes in colonic mucosa and fecal exfoliated cells through the use of edgeR and functional analysis with Ingenuity Pathway Analysis. We used 16S ribosomal RNA gene (V1-V3) analysis to characterize the fecal microbiome, and measured END and ENL in 24-h urine samples by gas chromatography-mass spectrometry. RESULTS We detected 32 DE genes (false discovery rate <0.05) in the exfoliome, but none in the mucosal biopsies, in response to 60 d of lignan supplement compared with placebo. Statistically significant associations were detected between ENL excretion and fecal microbiome measured at baseline and at the end of the intervention periods. Further, we detected DE genes in colonic mucosa and exfoliome between low- and high-ENL excreters. Analysis of biopsy samples indicated that several anti-inflammatory upstream regulators, including transforming growth factor β and interleukin 10 receptor, were suppressed in low-ENL excreters. Complementary analyses in exfoliated cells also suggested that low-ENL excreters may be predisposed to proinflammatory cellular events due to upregulation of nuclear transcription factor κB and NOS2, and an inhibition of the peroxisome proliferator-activated receptor γ network. CONCLUSIONS These results suggest that ENL or other activities of the associated gut microbial consortia may modulate response to a dietary lignan intervention. This has important implications for dietary recommendations and chemoprevention strategies. This study was registered at clinicaltrials.gov as NCT01619020.

Ranking feature sets for phenotype classification based on gene expression is a challenging issue in cancer bioinformatics. When the number of samples is small, all feature selection algorithms are known to be unreliable, producing significant error, and error estimators suffer from different degrees of imprecision. The problem is compounded by the fact that the accuracy of classification depends on the manner in which the phenomena are transformed into data by the measurement technology. Because next-generation sequencing technologies amount to a nonlinear transformation of the actual gene or RNA concentrations, they can potentially produce less discriminative data relative to the actual gene expression levels. In this study, we compare the performance of ranking feature sets derived from a model of RNA-Seq data with that of a multivariate normal model of gene concentrations using 3 measures: (1) ranking power, (2) length of extensions, and (3) Bayes features. This is the model-based study to examine the effectiveness of reporting lists of small feature sets using RNA-Seq data and the effects of different model parameters and error estimators. The results demonstrate that the general trends of the parameter effects on the ranking power of the underlying gene concentrations are preserved in the RNA-Seq data, whereas the power of finding a good feature set becomes weaker when gene concentrations are transformed by the sequencing machine.

Linguistic flexibility around non-predetermined expressions is important for more effective human–robot face-to-face interaction. In the past, most robots have been fitted with a limited and supervised response process and programmed with certain responses for predetermined words or sentences. As a result, implementing viable robot-based recommendation services has been difficult. The purpose of this paper is to propose a text-mining approach to flexible robot-based recommendation services in which, when the robot encounters linguistic expressions that differ substantially from the programmed linguistic database, flexible responses are generated based on understanding of several external corpora and a knowledge-learning process. This study combines two text-mining methods, TF-IDF and LDA, to generate flexible communication, which enables a robot to respond with recommendation content that is not pre-programmed. The results of our analysis suggest that the proposed combined approach outperforms the TF-IDF and LDA methods in terms of overall accuracy and F-score.

BACKGROUND:Oxysterols, oxygenated by-products of cholesterol biosynthesis, play roles in various physiological and pathological systems. However, the effects of oxysterols on periodontal regeneration are unknown. This study investigated the effects of the specific oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol (SS) on the regeneration of periodontal tissues using in-vitro periodontal ligament stem cells (PDLSCs) and in-vivo models of alveolar bone defect.METHODS:To evaluate the effects of the combined oxysterols on PDLSC biology, we studied the SS-induced osteogenic differentiation of PDLSCs by assessing alkaline phosphatase activity, intracellular calcium levels [Ca2+]i, matrix mineralization, and osteogenic marker mRNA expression and protein levels. To verify the effect of oxysterols on alveolar bone regeneration, we employed tooth extraction bone defect models.RESULTS:Oxysterols increased the osteogenic activity of PDLSCs compared with the control group. The expression of liver X receptor (LXR) α and β, the nuclear receptors for oxysterols, and their target gene, ATP-binding cassette transporter A1 (ABCA1), increased significantly during osteogenesis. Oxysterols also increased protein levels of the hedgehog (Hh) receptor Smo and the transcription factor Gli1. We further confirmed the reciprocal reaction between the LXRs and Hh signaling. Transfection of both LXRα and LXRβ siRNAs decreased Smo and Gli1 protein levels. In contrast, the inhibition of Hh signaling attenuated the LXRα and LXRβ protein levels. Subsequently, SS-induced osteogenic activity of PDLSCs was suppressed by the inhibition of LXRs or Hh signaling. The application of SS also enhanced bone formation in the defect sites of in-vivo models, showing equivalent efficacy to recombinant human bone morphogenetic protein-2.CONCLUSIONS:These findings suggest that a specific combination of oxysterols promoted periodontal regeneration by regulating PDLSC activity and alveolar bone regeneration.

Particularly in the healthcare service domain, social robots are expected to be good assistants, advisers, or practitioners. To increase the effectiveness of healthcare services provided by social robots, patients must comply with their requests. Research is plentiful on what makes patients comply with healthcare advice. In this paper, which is based on Bulgurcu’s study of rationality-based beliefs, command-compliance theory, and social exchange theory, we propose a research model of compliance during interaction with social robots, examining beliefs about and overall assessments of the consequences of complying with robot requests and extending the findings of previous studies to the setting of healthcare services. We specifically investigate the perceived level of politeness in robots’ speech and gestures as a determinant of compliance intention. Using a social robot, NAO, as a provider of healthcare services, we conducted an experiment. The results suggest that the aforementioned theories are useful in understanding user behaviors toward social robots in a healthcare service setting. Interestingly, and unlike in other settings, the perceived level of politeness of a social robot in a healthcare service setting negatively affects the perceived benefit of compliance, and, hence, intention to comply. A lower politeness level is closer to a command or strong recommendation than a suggestion or causal recommendation, which is common in shopping, tourism, or convention settings. The findings of this study imply that polite behavior from a social robot is an important factor in the compliance of healthcare service users. Direct speech with polite gestures is the most effective way to increase patient compliance in with healthcare advice provided by social robots in healthcare settings. However, higher levels of politeness do not always increase patients’ intention to comply.

For more realistic human-robot interaction, a robot should be able to flexibly respond to human's linguistic expressions that are not predefined in situations of face-to-face communication. However, most robots currently employ a limited response method in which they only react when the human speaks predefined words or sentences in a dictionary. This has been regarded as a limitation to the practical application of robots in real life. In this study, a text mining-based recommendation method was developed for robots to understand the meaning of exceptional human speech and obtain knowledge by using many external corpora with related data or knowledge based on the content of human speech. Tf-idf and LDA are combined to increase the recommendation accuracy.

Schizophrenia is a chronic psychotic disorder characterized by positive, negative, and cognitive symptoms. Primary treatments for schizophrenia relieve the positive symptoms but are less effective against the negative and cognitive symptoms. In the present study, we investigated whether maslinic acid, isolated from Syzygium aromaticum (clove), can ameliorate schizophrenia-like behaviors in mice induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. After maslinic acid treatment in the MK-801 model, we examined the behavioral alteration and signaling pathways in the prefrontal cortex. Mice were treated with maslinic acid (30 mg/kg), and their behaviors were evaluated through an array of behavioral tests. The effects of maslinic acid were also examined in the signaling pathways in the prefrontal cortex. A single administration of maslinic acid blocked the MK-801-induced hyperlocomotion and reversed the MK-801-induced sensorimotor gating deficit in the acoustic startle response test. In the social novelty preference test, maslinic acid ameliorated the social behavior deficits induced by MK-801. The MK-801-induced attention and recognition memory impairments were also alleviated by a single administration of maslinic acid. Furthermore, maslinic acid normalized the phosphorylation levels of Akt-GSK-3β and ERK-CREB in the prefrontal cortex. Overall, maslinic acid ameliorated the schizophrenia-like symptoms induced by MK-801, and these effects may be partly mediated through Akt-GSK-3β and ERK-CREB activation. These findings suggest that maslinic acid could be a candidate for the treatment of several symptoms of schizophrenia, including positive symptoms, sensorimotor gating disruption, social interaction deficits, and cognitive impairments.

Swertisin, a plant-derived C-glucosylflavone, is known to have antidiabetic, anti-inflammatory and antioxidant effects. In the present study, we investigated in mice the effects of swertisin on glutamatergic dysfunction induced by dizocilpine (MK-801), a non-competitive N-methyl-D-aspartate receptor antagonist. In the Acoustic Startle Response test, their MK-801-induced (given 0.2 mg/kg i.p.) pre-pulse inhibition deficit was significantly attenuated by the administration of swertisin (30 mg/kg p.o.). In the Novel Object Recognition Test, the recognition memory impairments that were induced by MK-801 (0.2 mg/kg, given i.p.) were also reversed by administration of swertisin (30 mg/kg p.o.). In addition, swertisin normalized the MK-801-induced elevation of phosphorylation levels of Akt and GSK-3β signaling molecules in the prefrontal cortex. These results indicated that swertisin may be useful in managing the symptoms of schizophrenia, including sensorimotor gating disruption and cognitive impairment, and that these behavioral outcomes may be related to Akt-GSK-3β signaling in the prefrontal cortex.

The strength of associations between various exposures (e.g., diet, tobacco, chemopreventive agents) and colorectal cancer risk may partially depend on the complex interaction between epithelium and stroma across anatomic subsites. Currently, baseline data describing genome-wide coding and long noncoding gene expression profiles in the healthy colon specific to tissue type and location are lacking. Therefore, colonic mucosal biopsies from 10 healthy participants who were enrolled in a clinical study to evaluate effects of lignan supplementation on gut resiliency were used to characterize the site-specific global gene expression signatures associated with stromal vs. epithelial cells in the sigmoid colon and rectum. Using RNA-seq, we demonstrate that tissue type and location patterns of gene expression and upstream regulatory pathways are distinct. For example, consistent with a key role of stroma in the crypt niche, mRNAs associated with immunoregulatory and inflammatory processes (i.e., CXCL14, ANTXR1), smooth muscle contraction (CALD1), proliferation and apoptosis (GLP2R, IGFBP3), and modulation of extracellular matrix (MMP2, COL3A1, MFAP4) were all highly expressed in the stroma. In comparison, HOX genes (HOXA3, HOXD9, HOXD10, HOXD11, and HOXD-AS2, a HOXD cluster antisense RNA 2), and WNT5B expression were also significantly higher in sigmoid colon compared with the rectum. These findings provide strong impetus for considering colorectal tissue subtypes and location in future observational studies and clinical trials designed to evaluate the effects of exposures on colonic health.

This study empirically investigates the factors affecting compliance with robot requests in task-oriented environments such as registration guide services in a hospital setting in which compliance is important for patient treatment. We examine the relative impact of interaction time, task understanding, and homophily on compliance. The results suggest that task understanding and interaction time are negatively related with intention to comply. However, homophily is not significantly related to intention to comply.

Domestic and international energy and eco-friendly companies take advantage of social media for image enhancement and product promotion. However, there were no in-depth empirical analysis to verify specific effectiveness of social media use in these sectors. The purpose of this study is to reveal the key factors that are considered to use social media effectively for energy and eco-friendly companies. For this purpose, we regarded the effectiveness of social media as Post Awareness and Word of Mouth. Characteristics of social media as a medium were measured separately, media richness and media genre, as independent variables of social media effectiveness. We investigated 413 posts in Facebook brand page of energy and eco-friendly companies and conducted a content analysis. As a result, post awareness of users was greater when post has richer media such as video. For media genre, word of mouth appeared to be greater when the posts provide information.

Efficient resource management strategies are important for multiuser multimedia applications, as they are often serviced over resource-constrained and shared network infrastructure. Moreover, an acceptable level of quality e.g., Quality of Service (QoS) should be guaranteed. In this paper, we consider a game-theoretic resource management strategy, where the bargaining solutions are deployed in the resource allocation. We are in particular interested in the Nash Bargaining Solution (NBS) that can allocate resources in a fair and optimal way, while explicitly considering the achieved utility. Finding the NBS, however, is a challenging task due to its potentially high computational complexity, especially when a large number of users and the large amount of resources are available. In order to overcome the problem, we propose an iterative approach that requires significantly lower computational complexity compared to the conventional approach. The proposed approach decomposes the bargaining problem into sub-bargaining problems, where a sub-bargaining problem considers smaller feasible set and computes the corresponding sub-NBS. This step is iteratively repeated for successive sub-bargaining problems until the NBS is obtained. We show that the proposed sub-NBS approaches the NBS with a small error while significantly reducing the complexity required to find the NBS.