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Processing-in-memory (PIM) comprises computational logic in the memory domain. It is the most promising solution to alleviate the memory bandwidth problem in deep neural network (DNN) processing. The hybrid memory cube (HMC), a 3D stacked memory structure, can efficiently implement the PIM architecture by maximizing the existing legacy hardware. To accelerate DNN inference, multiple HMCs can be connected, and data-independent tasks can be assigned to processing elements (PEs) within each HMC. However, owing to the packet-switched network structure, inter-HMC interconnects exhibit variable and unpredictable latencies depending on the data transmission path and link contention. A well-designed task schedule using context switching can effectively hide communication latency and improve PE utilization. Nevertheless, as the number of HMC increases, the variability of a wide range of inter-HMC communication latencies causes frequent context switching, degrading overall performance. This paper proposes a DNN task scheduling that can effectively utilize task parallelism by reducing the communication latency variance owing to HMC interconnect characteristics. Task partitions are generated to exploit parallelism while providing inter-HMC traffic within the sustainable link bandwidth. Task-to-HMC mapping is performed to hide the average communication latency of intermediate DNN processing results. A task schedule is generated using retiming to accelerate DNN inference while maximizing resource utilization. The effectiveness of the proposed method was verified through simulations using various realistic DNN applications performed on a ZSim x86-64 simulator. The simulations revealed that DNN processing with the proposed scheduling improved the DNN processing speed by reducing the processing time by 18.19% over conventional methods where each HMC operated independently.

Objectives Adult attention-deficit/hyperactivity disorder (ADHD) is an important mental health problem that needs resolution, especially considering the high rates of ADHD continuation from childhood to adolescence/adulthood and the high prevalence of ADHD in adults. Adults with ADHD have lifelong negative impacts and require close monitoring with long-term follow-up. Hence, the establishment of a Korean practice parameter for adult ADHD is necessary to minimize discontinuation of treatment and enable information sharing among Korean mental health professionals. Methods The Korean practice parameter was developed using an evidence-based approach consisting of expert consensus survey coupled with literature review. Results According to the expert consensus survey, the most commonly used diagnostic methods were clinical psychiatric interview (20.66%) and self-report scales (19.25%) followed by attention (14.71%) and psychological tests (14.24%). Key evaluation instruments currently available in Korea are the World Health Organization Adult ADHD Self-Report Rating Scale, Korean Adult ADHD Rating Scale, Diagnostic Interview for ADHD in Adults, Barkley Deficits in Executive Functioning Scale for adults, Comprehensive Attention Test, Conners' Continuous Performance Test, and the subtests of Wechsler Adult Intelligence Scale, Digit Span and Letter-Number Sequencing. Although pharmacotherapy is recommended as the first-line of treatment for adult ADHD, we recommend that it be followed by a multimodal and multidisciplinary approach including psychoeducation, pharmacotherapy, cognitive behavior therapy and coaching. Conclusion The Korean practice parameter introduces not only general information for the diagnosis and treatment of adult ADHD on a global scale, but also the process of diagnosis and treatment options tailored to the Korean population.

The timely mobilization of hematopoietic stem and progenitor cells (HSPCs) is essential for maintaining hematopoietic and tissue leukocyte homeostasis. Understanding how HSPCs migrate between bone marrow (BM) and peripheral tissues is of great significance in the clinical setting, where therapeutic strategies for modulating their migration capacity determine the clinical outcome. Here, we identify an epigenetic regulator, Phc2, as a critical modulator of HSPC trafficking. The genetic ablation of Phc2 in mice causes a severe defect in HSPC mobilization through the derepression of Vcam1 in bone marrow stromal cells (BMSCs), ultimately leading to a systemic immunodeficiency. Moreover, the pharmacological inhibition of VCAM-1 in Phc2-deficient mice reverses the symptoms. We further determine that Phc2-dependent Vcam1 repression in BMSCs is mediated by the epigenetic regulation of H3K27me3 and H2AK119ub. Together, our data demonstrate a cell-extrinsic role for Phc2 in controlling the mobilization of HSPCs by finely tuning their bone marrow niche., Mobilization of hematopoietic stem and progenitor cells (HSPCs) into the circulation is essential for maintaining homeostasis. Here, the authors show that Phc2 in bone marrow stromal cells represses the cell adhesion molecule Vcam1 and facilitates mobilization of HSPCs through regulation of epigenetic marks.

Multi-level cell (MLC) phase-change memory (PCM) is an attractive solution for next-generation memory that is composed of resistance-based nonvolatile devices. MLC PCM is superior to dynamic random-access memory (DRAM) with regard to scalability and leakage power. Therefore, various studies have focused on the feasibility of MLC PCM-based main memory. The key challenges in replacing DRAM with MLC PCM are low reliability, limited lifetime, and long write latency, which are predominantly affected by the most error-vulnerable data pattern. Based on the physical characteristics of the PCM, where the reliability depends on the data pattern, a tri-level-cell (3LC) PCM has significantly higher performance and lifetime than a four-level-cell (4LC) PCM. However, a storage density is limited by binary-to-ternary data mapping. This paper introduces error-vulnerable pattern-aware binary-to-ternary data mapping utilizing 3LC PCM without an error-correction code (ECC) to enhance the storage density. To mitigate the storage density loss caused by the 3LC PCM, a two-way encoding is applied. The performance degradation is minimized through parallel encoding. The experimental results demonstrate that the proposed method improves the storage density by 17.9%. Additionally, the lifetime and performance are enhanced by 36.1% and 38.8%, respectively, compared with those of a 4LC PCM with an ECC.

Background So far, studies on workplace mental health have only focused on work-related environmental risk factors, disregarding both protective and individual factors of employees. Therefore, we aimed to identify character strengths that act as protective factors against depressive moods and suicidality in Korean employees. Methods In total, 84 male and 151 female employees (aged 19–50 years) reported their sociodemographic characteristics; depressive symptoms, as measured by the Beck Depression Inventory-II; suicidality, as measured by the Korean version of the MINI International Neuropsychiatric Interview suicidality module; and character strengths, as measured by the 24 Character Strength Alphas on the Values in Action Survey-72. We conducted a hierarchical logistic regression, in which depressive mood and suicidality served as the categorical outcome variables. Results In females, scores on the “curiosity” (B = 1.107, Wald = 10.207, odds ratio = 3.026, p = .001) and “love” (B = .862, Wald = 5.767, odds ratio = 2.367, p = .016) sub scales of the 24 Character Strength Alphas on the Values in Action Survey-72 were statistically significant predictors of having depressive mood. Additionally, females’ scores on “judgment” (B = − 1.405, Wald = 5.663, odds ratio = .245, p = .017) and “kindness” (B = − 1.456, Wald = 6.486, odds ratio = .233, p = .011) were protective factors against suicidality. In males, the “love” (B = 1.746, Wald = 4.279, odds ratio = 5.729, p = .039) score was a predictor of having depressive mood, while “teamwork” (B = − 2.204, Wald = 4.666, odds ratio = .110, p = .031) and “creativity” (B = − 1.384, Wald = 4.202, odds ratio = .251, p = .040) scores were protective factors against having depressive mood and suicidality, respectively. Conclusions We suggest that focusing on “judgement” and “kindness” in female employees, and “teamwork” and “creativity” in male employees, and engaging in activities that use these strengths at the workplace can be protective factors against depression and suicidality. Future research should focus on developing interventions to promote these character strengths among employees at the workplace.

Objective The aim of the present study was to evaluate the role of comorbid psychiatric symptoms on quantitative electroencephalogram (QEEG) activities in boys with the attention deficit/hyperactivity disorder (ADHD). Methods All participants were male students in the second, third or fourth grade in elementary school. Therefore, there were no significant differences in age or sex. Participants with ADHD were assigned to one of three groups: pure ADHD (n=22), ADHD with depressive symptoms (n=11), or ADHD with problematic internet use (n=19). The Korean version of the Children's Depression Inventory and the Korean Internet Addiction Self-scale were used to assess depressive symptoms and problematic internet use, respectively. Resting-state EEG during eyes closed was recorded, and the absolute power of five frequency bands was analyzed: delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), and gamma (30-50 Hz). Results The ADHD with problematic internet use group showed decreased absolute theta power at the central and posterior region compared with the pure ADHD group. However, The ADHD with depressive symptoms group showed no significant differences compared with the other groups. Conclusion These findings will contribute to a better understanding of brain-based electrophysiological changes in children with ADHD in accordance with comorbid psychiatric symptoms.

Objective Recent studies of online game addiction have suggested that social interaction and impulsivity are critical factors for the etiology and progress of online game addiction. We hypothesized that the genre of the online game is associated with impulsivity and sociality in individuals with online game addictions. Methods In total, 212 patients with problematic online game playing were divided into four groups by game genre: 1) massive multiplayer online role playing game (MMORPG), 2) real-time strategy (RTS), 3) first-person shooter (FPS), and 4) other. Their symptoms and characteristics were assessed using 8 scales and 2 tests to estimate self-esteem, impulsiveness, comorbidity, social interaction status, and cognitive function. Results The mean social anxiety score was highest in the MMORPG group and lowest in the FPS group. The mean self-esteem score was highest in the RTS group. Social anxiety score was positively correlated with Internet addiction score in the MMORPG group, and the self-esteem score was positively correlated with Internet addiction score in the RTS group. Conclusion The genre of online game was not associated with impulsivity, but social anxiety status varied significantly with game genre, and differences in social anxiety were especially pronounced in patients playing the MMORPG (highest social anxiety) and FPS (lowest social anxiety) game genres. In addition, self-esteem was highest in the RTS game genre.

Pathogen expulsion from the gut is an important defense strategy against infection, but little is known about how interaction between the intestinal microbiome and host immunity modulates defecation. In Drosophila melanogaster, dual oxidase (Duox) kills pathogenic microbes by generating the microbicidal reactive oxygen species (ROS), hypochlorous acid (HOCl) in response to bacterially excreted uracil. The physiological function of enzymatically generated HOCl in the gut is, however, unknown aside from its anti-microbial activity. Drosophila TRPA1 is an evolutionarily conserved receptor for reactive chemicals like HOCl, but a role for this molecule in mediating responses to gut microbial content has not been described. Here we identify a molecular mechanism through which bacteria-produced uracil facilitates pathogen-clearing defecation. Ingestion of uracil increases defecation frequency, requiring the Duox pathway and TrpA1. The TrpA1(A) transcript spliced with exon10b (TrpA1(A)10b) that is present in a subset of midgut enteroendocrine cells (EECs) is critical for uracil-dependent defecation. TRPA1(A)10b heterologously expressed in Xenopus oocytes is an excellent HOCl receptor characterized with elevated sensitivity and fast activation kinetics of macroscopic HOCl-evoked currents compared to those of the alternative TRPA1(A)10a isoform. Consistent with TrpA1’s role in defecation, uracil-excreting Erwinia carotovora showed higher persistence in TrpA1-deficient guts. Taken together, our results propose that the uracil/Duox pathway promotes bacteria expulsion from the gut through the HOCl-sensitive receptor, TRPA1(A)10b, thereby minimizing the chances that bacteria adapt to survive host defense systems., Author Summary The amount and pattern of defecation are often determined by the bacterial composition in the gut, and can have a significant impact on human health. It is however unknown how changes in the bacterial community affect defecation. A chemical defense system called the Duox pathway is known to kill ill-causing bacteria in the gut by producing chlorine bleach. Our study reveals that the bleach does not stop there, working further to promote expulsion of the bacteria from the gut through a sensitive bleach detector. Moreover, in the gut deficient for the bleach detector, the bacteria not only stayed longer, but also opportunistically survived the bleach that they encounter afterwards. This is the first identification of a mechanism illustrating how important it is that gut defense systems control defecation, and helps explain why troubles in the gut cause changes in defecation.

Porcine circovirus type 2 (PCV2) is the primary causative agent of postweaning multisystemic wasting syndrome, which leads to serious economic losses in the pig industry worldwide. While the molecular basis of PCV2 replication and pathogenicity remains elusive, it is increasingly apparent that the microRNA (miRNA) pathway plays a key role in controlling virus-host interactions, in addition to a wide range of cellular processes. Here, we employed Solexa deep sequencing technology to determine which cellular miRNAs were differentially regulated after expression of each of three PCV2-encoded open reading frames (ORFs) in porcine kidney epithelial (PK15) cells. We identified 51 ORF1-regulated miRNAs, 74 ORF2-regulated miRNAs, and 32 ORF3-regulated miRNAs that differed in abundance compared to the control. Gene ontology analysis of the putative targets of these miRNAs identified transcriptional regulation as the most significantly enriched biological process, while KEGG pathway analysis revealed significant enrichment for several pathways including MAPK signaling, which is activated during PCV2 infection. Among the potential target genes of ORF-regulated miRNAs, two genes encoding proteins that are known to interact with PCV2-encoded proteins, zinc finger protein 265 (ZNF265) and regulator of G protein signaling 16 (RGS16), were selected for further analysis. We provide evidence that ZNF265 and RGS16 are direct targets of miR-139-5p and let-7e, respectively, which are both down-regulated by ORF2. Our data will initiate further studies to elucidate the roles of ORF-regulated cellular miRNAs in PCV2-host interactions. Electronic supplementary material The online version of this article (doi:10.1186/s13567-015-0172-5) contains supplementary material, which is available to authorized users.

Introduction Dopamine receptor polymorphisms have been associated with specific patterns of novelty seeking (NS) temperamental nature and frontal executive function. In addition, carriers of dopamine receptor type 2 (DRD2)–TaqI A1 have been hypothesized to be potentially vulnerable to addictive behaviors. In the present study, the association between dopamine D2 polymorphisms, NS, and frontal executive function was studied. Methods Thirty-seven methamphetamine (MA)–dependent subjects and 40 healthy comparison subjects participated in the current study. The severity of addiction, NS temperament, and frontal executive functions were measured using the Addiction Severity Index, the NS subscale in the Temperament and Character Inventory, and the Wisconsin Card Sorting Test, respectively. All subjects were genotyped with regard to DRD2-TaqI polymorphisms. Results The prevalence of DRD2-TaqI A1 allele polymorphisms was greater in the MA-abuser group than in the comparison group. Patients with MA dependence also had higher NS characteristics and high scores in total trials, errors, and perseverative errors of the Wisconsin Card Sorting Test than comparison subjects. Within patients with MA dependence, the subgroup of DRD2-TaqI A1 carrier had greater NS scores relative to those without, whereas there was only a trend level of lower frontal executive function in the first subgroup. Conclusion In the present study, the MA-dependent patients with DRD2-TaqI A1 allele had significantly greater NS scores and lower frontal executive function with a trend level than those without. These preliminary results suggest that MA-dependent patients may have the possibility of genetic and biogenic vulnerability to MA.

Introduction Social network analysis has emerged as a promising tool in modern social psychology. This method can be used to examine friend-based social relationships in terms of network theory, with nodes representing individual students and ties representing relationships between students (e.g., friendships and kinships). Using social network analysis, we investigated whether greater severity of ADHD symptoms is correlated with weaker peer relationships among elementary school students. Methods A total of 562 sixth-graders from two elementary schools (300 males) provided the names of their best friends (maximum 10 names). Their teachers rated each student’s ADHD symptoms using an ADHD rating scale. Results The results showed that 10.2% of the students were at high risk for ADHD. Significant group differences were observed between the high-risk students and other students in two of the three network parameters (degree, centrality and closeness) used to assess friendship quality, with the high-risk group showing significantly lower values of degree and closeness compared to the other students. Moreover, negative correlations were found between the ADHD rating and two social network analysis parameters. Conclusion Our findings suggest that the severity of ADHD symptoms is strongly correlated with the quality of social and interpersonal relationships in students with ADHD symptoms.

Jun Won Kim,1,2 KounSeok Lee,3 Young Sik Lee,4 Doug Hyun Han,4 Kyung Joon Min,4 Sung Hwan Song,5 Ga Na Park,6 Ju Young Lee,1 Jae Ock Kim5 1Division of Child and Adolescent Psychiatry, Department of Neuropsychiatry, College of Medicine, Seoul National University, Seoul, South Korea; 2Department of Psychiatry, Graduate School, Chung-Ang University, Seoul, South Korea; 3Department of Psychiatry, Samsung Medical Center, Seoul, South Korea; 4Department of Psychiatry, Chung-Ang University, College of Medicine, Seoul, South Korea; 5Department of Psychiatry, Gongju National Hospital, Gongju, South Korea; 6Department of Special Education, Graduate School, Dankook University, Jukjeon, South Korea Purpose: Low socioeconomic status is an important risk factor for child psychiatric problems. Low socioeconomic status is also associated with psychiatric problems later in life. We investigated the effects of group bullying on clinical characteristics and psychopathology in elementary school students using child-welfare facilities.Methods: Three hundred and fifty-eight elementary school students using child-welfare facilities were recruited. The School Bullying Self Rating Questionnaire was used to assess group bullying. To evaluate related psychopathology, the Children’s Problem-Behavior Screening Questionnaire, the Children’s Depression Inventory, the Beck Anxiety Inventory, the Suicidal Ideation Questionnaire, Young’s Internet Addiction Scale, and Conners–Wells’ Adolescent Self-Report Scale were applied. Samples were classified according to school grade (lower or upper), and each group’s characteristics were compared as they related to bullying victims versus non-victims.Results: The prevalence rate of group bullying was 22% in the lower-grade group and 12% in the higher-grade group. Bullying victims in lower grades reported high somatization, depressive symptoms, Internet addiction, and attention deficit hyperactivity disorder tendencies, whereas those in upper grades reported cognitive problems, symptoms of depression and anxiety, suicidal ideation, Internet addiction, and attention deficit hyperactivity disorder tendencies. Somatization and depressive symptoms were significant predictors of bullying in the lower-grade group, and anxiety was a significant predictor of bullying in the upper-grade group.Conclusion: This study demonstrated that elementary school students using child-welfare facilities might have an increased risk of being bullied and that bullying victims may have different psychopathologies depending on their ages. Keywords: socioeconomic status, somatization, depression, anxiety

Recent brain imaging studies suggested that both the frontal and temporal cortices are important candidate areas for mediating the symptoms of internet addiction. We hypothesized that deficits of prefrontal and temporal cortical function in patients with on-line game addiction (PGA) would be reflected in decreased levels of N-acetyl aspartate (NAA) and cytosolic, choline containing compound (Cho). Seventy three young PGA and 38 age and sex matched healthy control subjects were recruited in the study. Structural MR and (1)H MRS data were acquired using a 3.0 T MRI scanner. Voxels were sequentially placed in right frontal cortex and right medial temporal cortices. In the right frontal cortex, the levels of NAA in PGA were lower than those in healthy controls. In the medial temporal cortex, the levels of Cho in PGA participants were lower than those observed in healthy controls. The Young Internet Addiction Scale (YIAS) scores and perseverative responses in PGA were negatively correlated with the level of NAA in right frontal cortex. The Beck Depressive Inventory (BDI) scores in the PGA cohort were negatively correlated with Cho levels in the right temporal lobe. To the best of our knowledge, this is the first MRS study of individuals with on-line game addiction. Although, the subjects with on-line game addiction in the current study were free from psychiatric co-morbidity, patients with on-line game addiction appear to share characteristics with ADHD and MDD in terms of neurochemical changes in frontal and temporal cortices.

The Microprocessor plays an essential role in canonical miRNA biogenesis by facilitating cleavage of stem-loop structures in primary transcripts to yield pre-miRNAs. Although miRNA biogenesis has been extensively studied through biochemical and molecular genetic approaches, it has yet to be addressed to what extent the current miRNA biogenesis models hold true in intact cells. To address the issues of in vivo recognition and cleavage by the Microprocessor, we investigate RNAs that are associated with DGCR8 and Drosha by using immunoprecipitation coupled with next-generation sequencing. Here, we present global protein-RNA interactions with unprecedented sensitivity and specificity. Our data indicate that precursors of canonical miRNAs and miRNA-like hairpins are the major substrates of the Microprocessor. As a result of specific enrichment of nascent cleavage products, we are able to pinpoint the Microprocessor-mediated cleavage sites per se at single-nucleotide resolution. Unexpectedly, a 2-nt 3' overhang invariably exists at the ends of cleaved bases instead of nascent pre-miRNAs. Besides canonical miRNA precursors, we find that two novel miRNA-like structures embedded in mRNAs are cleaved to yield pre-miRNA-like hairpins, uncoupled from miRNA maturation. Our data provide a framework for in vivo Microprocessor-mediated cleavage and a foundation for experimental and computational studies on miRNA biogenesis in living cells.

Background The pig, Sus scrofa domestica includes both the miniature and commercial domestic breed. These animals have influenced the human life and economies and have been studied throughout history. Although the miniature breeds are more recent and have increasingly been used in a variety of biomedical studies, their cell lines have rarely been established. Therefore, we sought to establish primary and immortal cell lines derived from both the miniature and domestic pig to better enable insight into possible in vivo growth differences. Results The in vitro lifespan of primary domestic pig fibroblast (PF) and miniature pig fibroblast (MPF) cells using a standard 3T3 protocol was determined. Both of the primary PF and MPF cells were shown to have a two-step replicative senescence barrier. Primary MPF cells exhibited a relatively shorter lifespan and slower proliferation rate compared to those of primary PF cells. Beyond senescence barriers, lifespan-extended PF and MPF cells were eventually established and indicated spontaneous cellular immortalization. In contrast to the immortalized PF cells, immortal MPF cells showed a transformed phenotype and possessed more frequent chromosomal abnormalities and loss of p53 regulatory function. The lifespan of primary MPF and PF cells was extended by inactivation of the p53 function using transduction by SV40LT without any detectable senescent phenotype. Conclusion These results suggest that p53 signaling might be a major determinant for the replicative senescence in the MPF cells that have the shorter lifespan and slower growth rate compared to PF cells in vitro.

The RNase III enzyme Dicer processes RNA into siRNAs and miRNAs, which direct a RNA-induced silencing complex (RISC) to cleave mRNA or block its translation (RNAi). We have characterized mutations in the Drosophila dicer-1 and dicer-2 genes. Mutation in dicer-1 blocks processing of miRNA precursors, whereas dicer-2 mutants are defective for processing siRNA precursors. It has been recently found that Drosophila Dicer-1 and Dicer-2 are also components of siRNA-dependent RISC (siRISC). We find that Dicer-1 and Dicer-2 are required for siRNA-directed mRNA cleavage, though the RNase III activity of Dicer-2 is not required. Dicer-1 and Dicer-2 facilitate distinct steps in the assembly of siRISC. However, Dicer-1 but not Dicer-2 is essential for miRISC-directed translation repression. Thus, siRISCs and miRISCs are different with respect to Dicers in Drosophila.