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Near-threshold computing is essential for energy-efficient operation of VLSI systems, but wide performance variation and nonlinearity to process variations block the proliferation. To cope with this, in this paper, we propose a holistic hardware performance monitoring methodology for accurate timing prediction in a near-threshold voltage regime. Precisely, (1) we formulate the problem of finding an efficient configuration of monitoring circuits into an instance of optimal experiment design problem and (2) propose a new timing prediction flow, consisting of statistical estimation of FEOL and BEOL process variations and a neural network based timing inference model. For accurate control of timing margin and overcoming simulation-silicon discrepancies, (3) we introduce uncertainty learning in the prediction model construction and calibrate it through transfer learning. Furthermore, (4) we avoid time-consuming SPICE simulations in our methodology by employing efficient but accurate surrogate models. Through simulations using a 28nm industry PDK and DK characterized at 0.6V operation, it is shown that our methodology is highly effective, reducing the average prediction pessimism of maximum delay by 77.9% over conventional signoff results while respecting target prediction yield. Besides, for test chips fabricated using a 10nm process, we demonstrated that our holistic approach from design to post-silicon phase in conjunction with adaptive voltage scaling reduces dynamic power consumption by 28.2% 28.8% on average, in comparison with typical supply voltage operation.

Low power design by near-threshold voltage (NTV) operation is very attractive since it affords to considerably mitigate the sharp increase of power dissipation. However, one key barrier for the use of NTV operation is the significant increase of the SRAM failure. In this work, we propose an on-chip SRAM monitoring methodology that is able to accurately predict the minimum voltage, Vddmin, on each die that does not cause SRAM read and write failures, which are majorities of SRAM failures, under a target confidence level. Precisely, we propose an SRAM monitor, from which we measure a maximum voltage, Vfail, that causes functional failure on that SRAM monitor. Then, we propose a novel methodology of inferring SRAM V ˆ d d m i n on each die from the measured Vfail of SRAM monitor on the same die where Vfail-Vddmin correlation table is built-up in design infra development phase, and V ˆ d d m i n can be directly derived from the measured Vfail referencing the correlation table in silicon production phase. Through experiments, we confirm that our proposed methodology is able to save leakage power by 10.45%, read energy by 4.99%, and write energy by 5.45% in SRAM bitcell array over that by applying a uniform minimum voltage for all dies while meeting the same yield constraint. In addition, the effect of IR drop and process variations of peripheral circuit on Vddmin prediction is taken into account by reflecting them on SRAM bitcell operation. We also solidify our Vddmin prediction methodology by considering the prevention of potential SRAM access failures for high-speed designs as well as the SRAM read and write failures.

This paper presents a deep neural network based test vector generation method for dynamic verification of memory devices. The proposed method is built on reinforcement learning framework, where the action is input stimulus on device pins and the reward is coverage score of target circuitry. The developed agent efficiently explores high-dimensional and large action space by using policy gradient method with A-nearest neighbor search, transfer learning, and replay buffer. The generated test vectors attained the coverage score of 100% for fifteen representative circuit blocks of modern DRAM design. The output vector length was only 7% of the human-created vector length.

Objective To compare the radiologic union rates between autogenous iliac crest bone graft (ICBG) and local bone graft in 1- to 3-level lumbar fusion. Methods We reviewed 178 consecutive patients who underwent 1- to 3-level lumbar fusion surgery because of lumbar spinal stenosis. Fusion status of the anterior or posterior column was evaluated by plain radiographs obtained at 24 months postoperatively. If at least either the anterior or posterior column was fused, that segment was regarded as having achieved fusion and was termed segment union. The definition of overall union was achieving union of all segments in a single patient. Results For each ICBG group and local bone graft group, fusion rate of the anterior and posterior column, and rate of the segments and overall union at postoperative 2 years were not different between the groups, regardless of surgery level. In the overall union rate according to the fusion level, the ICBG group showed constant overall fusion rate according to the fusion level (i.e., 96.9%, 96.9%, and 93.1% for 1-, 2-, and 3-level fusion), but tended to decrease with increasing level in the local bone graft group (100%, 95.8%, and 85.7% for 1-, 2-, and 3-level fusion, respectively) without statistically significant differences. Conclusions The union rate of 3-level fusion was not inferior to those of 1- or 2-level fusion in both ICBG and local bone graft patients. Local bone graft could be regarded as an adequate option for not only 1- or 2-level lumbar fusion but also 3-level lumbar fusion surgery.

We developed two-step thermoresponsive membranes that have two different lower critical solution temperatures. To achieve this, poly(2-dimethylaminoethyl methacrylate)-block-poly(N-isopropylacrylamide) (PDMAEMA-b-PNIPAM, PDN) was introduced into a polyethersulfone (PES) ultrafiltration membrane. The combined Fourier-transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, attenuated total reflection Fourier-transform infrared spectroscopy, and field-emission scanning electron microscopy results showed that PDN was successfully synthesized, and introduced into the PES membrane. The hydration capacity changes showed that the PES membrane with introduced PDN (PES/PDN) was temperature responsive, and that its pore structure changed. Water flux and protein separation experiments showed that the permeation properties of the PES/PDN membrane effectively changed, and protein separation was achieved based on pore structure changes in response to temperature changes. In particular, PES/PDN containing 5% PDN compared to PES separated water and three types of protein with high efficiency via three clear separation steps, at 30, 50, and 70 °C. In addition, the thermoresponsive polymer block in the PES/PDN membrane improved the flux recovery ratio from 29% to 69%.

Background Management of congenital heart disease (CHD) in developing countries is challenging because of limited access to healthcare facilities and socioeconomic limitations. We aimed to describe the recent experience with CHD at Children's Hospital of Lao People's Democratic Republic (PDR), the only pediatric referral hospital in the nation. Methods From July 2013 to November 2015, we performed 1,009 echocardiograms of 797 individuals who visited Children's Hospital and identified 213 CHD patients. Demographic characteristics, echocardiographic findings and the age when CHD was first diagnosed echocardiographically were compared by residential areas. Results Among the 213 patients, the most frequent anomalies, in descending order, were ventricular septal defect, atrial septal defect, patent ductus arteriosus, and tetralogy of Fallot. A moderate or severe CHD that requires surgery or intervention was detected in 137 patients; the median age at initial diagnosis was 6.0 months (IQR, 1.5–29.8). Among those with moderate or severe CHD, 89 patients were from rural areas and 48 from the capital area. Proportions of patients from rural areas who were older than 1 and 3 years when diagnosed were 46.1% and 32.6%, respectively. In contrast, patients from the capital area were diagnosed at significantly earlier ages: 16.7% at age >1 year and 6.2% at age >3 years (both P

Background To investigate the characteristics of patients with osteoporotic fractures (OF) who visited the emergency room, we analyzed the frequency and distribution of primary and secondary OF. Methods From March 2015 to April 2017, 406 patients with OF were assigned to wrist (W; n=132), spine (S; n=78), and hip (H; n=196) according to the site. All subjects were classified as having primary fracture or secondary fracture. Age, fracture site, the risk of future fracture using Fracture Risk Assessment Tool (FRAX) were compared. Results The mean age at fracture site was significantly different among the 3 groups, groups W (66.57±10.03), S (73.50±9.07), and H (78.50±7.72). The most common site of OF were in the order of wrist, spine, and hip with the increase of age. The FRAX scores significantly increased (P

This study was conducted to determine the residual amount of veterinary drugs such as meloxicam, flunixin, and tulathromycin in animal products (beef, pork, horsemeat, and milk). Veterinary drugs have been widely used in the rearing of livestock to prevent and treat diseases. A total of 152 samples were purchased from markets located in major Korean cities (Seoul, Busan, Incheon, Daegu, Daejeon, Gwangju, Ulsan and Jeju), including Jeju. Veterinary drugs were analyzed by liquid chromatography-tandem mass spectrometry according to the Korean Food Standards Code. The resulting data, which are located within 70-120% of recovery range and less than 20% of relative standard deviations, are in compliance with the criteria of CODEX. A total of five veterinary drugs were detected in 152 samples, giving a detection rate of approximately 3.3%; and no food source violated the guideline values. Our result indicated that most of the veterinary drug residues in animal products were below the maximum residue limits specified in Korea.

Citrin deficiency (CD) is a recessive genetic disorder caused by mutations in the citrin gene SLC25A13. CD causes various symptoms related to nutrient metabolism such as urea cycle failure, abnormal amino acid levels, and fatty liver. To understand the pathophysiology of CD, the molecular phenotypes were investigated using induced pluripotent stem cells derived from fibroblasts of CD patient (CD-iPSCs). In this study, we demonstrate that aberrant mitochondrial β-oxidation may lead to fatty liver in CD patients. CD-iPSCs normally differentiated into hepatocytes, similar to wild-type iPSCs (WT-iPSCs). However, hepatocytes derived from CD-iPSCs (CD-HLCs) did not exhibit ureogenesis. Cellular triglyceride and lipid granule levels were significantly increased in CD-HLCs compared with WT-HLCs. Peroxisome proliferator-activated receptor-α (PPAR-α) and its target genes which are involved in mitochondrial β-oxidation were downregulated in CD-HLCs, and treatment with a PPAR-α agonist partially reduced the lipid accumulation in CD-HLCs. In addition, the mitochondria in CD-HLCs exhibited abnormal morphologies. Based on these observations, we conclude that the lipid accumulation in CD-HLCs results from dysfunctional mitochondrial β-oxidation and abnormal mitochondrial structure.

Technology innovation plays an increasingly prominent role in addressing global environmental challenges. In particular, environmental technology innovation (environmental innovation) is the most powerful and realistic alternative to achieve environmental sustainability and sustainable development. A better understanding of how environmental innovation affects the environment and how the effect differs by country is needed. This study analyzes how environmental innovation affects environmental improvement by a dynamic panel model using the System Generalized Method of Moments (GMM) estimation. We use panel data from 33 high-income countries and 36 middle-income countries for the period 1996&ndash, 2011, to compare their environmental pollution patterns, and determine how environmental innovation affects air pollution reduction as measured by sulfur dioxide (SO2) and carbon dioxide (CO2) emissions. The results reveal that environmental innovation improves the environment in some countries over time. The effect is particularly beneficial in high income countries. It is evident that environmental innovations reduce SO2 and CO2 emissions in high-income countries with time interval, while it does not in middle-income countries. The study also identifies that the relationship between per capita income and SO2 and CO2 emissions has a different pattern between high- and middle-income countries. The inverted U-shaped pattern supporting the hypothesis of the Environmental Kuznets Curve (EKC) exists in high-income countries. The examination of the trade effect on pollution emissions provides mixed results, however, trade clearly increases SO2 and CO2 emissions in middle-income countries. This study contributes to empirical literatures on the effect of environmental innovation on environmental improvement. And it has significant implications for understanding the importance of direction and role of environmental innovation for environmental sustainability and sustainable development.

Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder caused by mutations in the extracellular signal-regulated kinase (ERK) signaling. However, little is known about how aberrant ERK signaling is associated with the defective bone development manifested in most CFC syndrome patients. In this study, induced pluripotent stem cells (iPSCs) were generated from dermal fibroblasts of a CFC syndrome patient having rapidly accelerated fibrosarcoma kinase B (BRAF) gain-of-function mutation. CFC-iPSCs were differentiated into mesenchymal stem cells (CFC-MSCs) and further induced to osteoblasts in vitro. The osteogenic defects of CFC-MSCs were revealed by alkaline phosphatase activity assay, mineralization assay, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. Osteogenesis of CFC-MSCs was attenuated compared to wild-type (WT)-MSCs. In addition to activated ERK signaling, increased p-SMAD2 and decreased p-SMAD1 were observed in CFC-MSCs during osteogenesis. The defective osteogenesis of CFC-MSCs was rescued by inhibition of ERK signaling and SMAD2 signaling or activation of SMAD1 signaling. Importantly, activation of ERK signaling and SMAD2 signaling or inhibition of SMAD1 signaling recapitulated the impaired osteogenesis in WT-MSCs. Our findings indicate that SMAD2 signaling and SMAD1 signaling as well as ERK signaling are responsible for defective early bone development in CFC syndrome, providing a novel insight on the pathological mechanism and therapeutic targets.

Ball-milled and chemically activated pitch-based carbon fibers (PCF) were prepared for use as electrode materials. Ball milling altered the structure of PCF from fibers to micro-sized particles with loss of porosity. In contrast, chemical activation using KOH facilitated the development of pore structures. The supercapacitive behavior of treated PCF was assessed using cyclic voltammetry and galvanostatic charge/discharge experiments in 6 M KOH electrolytic solution. BAPCF900, the sample subjected to combined ball milling and chemical treatment, activated at 900 °C, exhibited a specific capacitance of about 80 F/g at a current density of 0.2 A/g; this good capacitance is attributed to a specific surface area of 803 m2/g and a total pore volume of 0.352 cm3/g, and is related to the appropriate pore structure for electrode application, comprising mesopores and micropores.

Petroleum pitch is activated with KOH, and different concentrations of MnO2 nanoparticles are impregnated on petroleum pitch-based activated carbons with a simple chemical reaction. Fiber-like MnO2 is successfully grown on the surface of the activated carbons. The specific capacitance of A-PP-0.02 is 92 F/g in 0.5 M Na2SO4. This increase is due to the appropriate combination of the pore structure and MnO2 that allows electrolyte ions to easily reach the electrode. The results indicate that MnO2 is a promising metal oxide for increasing the specific capacitance of petroleum pitch-based activated carbons and can overcome the low energy density.

This article explores the perception and reasons for Korean students’ silence and low levels of oral participation in U.S. graduate programs. It analyzes a case study conducted with two Korean students currently attending graduate school in urban settings. The researcher conducted semi-structured interviews with the participants, using a constant comparisons method for data analysis. The study shows that the participants perceived themselves to be the quietest members of their classes. Reasons for silence included poor command of the English terms relevant for their discipline, influence of Korean classroom mannerisms, and face saving. However, the participants had a strong desire to contribute, which was revealed when they actively worked on an online discussion board. This implies the need for pedagogical tools to encourage and help these students actively speak up in U.S. classrooms.

Background : Atrial tachyarrhythmia is a major late complication in adult Fontan patients. This study examined the clinical features and risk factors of late intra-atrial reentrant tachyarrhythmia (IART) in adult patients after Fontan surgery and the mid-term outcome of Fontan conversion with or without antiarrhythmic surgery in these patients. Methods : We conducted a retrospective study on adult patients who were born before 1994 and survived at least 3months after a Fontan operation at Seoul National University Children's Hospital. Results : We followed 160 patients over 20.9±4.1years. Sustained atrial tachycardia was identified in 51 patients, and IART was found in 41, appearing a mean 13.6years after surgery. By the 25year follow-up, 40% had developed IART. The incidence of IART significantly increased over time. Patients with an atriopulmonary connection (APC) (n=65) had significantly longer follow-up duration and higher incidence of IART than patients with a lateral tunnel (n=86) or extracardiac conduit Fontan (n=9). On multivariate analysis, APC, sinus node dysfunction, and nonsustained atrial tachycardia were found to be significantly associated with IART. Twenty-four patients with IART underwent Fontan conversion. Over the follow-up period, IART severity scores in the 22 patients who survived after Fontan conversion decreased significantly, and New York Heart Association functional class significantly improved. On multivariate analysis, protein losing enteropathy and ventricular dysfunction were found to be significant risk factors for mortality. Conclusions : IART was common in adult Fontan patients, and Fontan conversion with or without antiarrhythmic surgery and pacemaker placement helped to control it.

Cardio-facio-cutaneous (CFC) syndrome is a developmental disorder caused by constitutively active ERK signaling manifesting mainly from BRAF mutations. Little is known about the role of elevated ERK signaling in CFC syndrome during early development. Here, we show that both SMAD1 and ERK signaling pathways may contribute to the developmental defects in CFC syndrome. Induced pluripotent stem cells (iPSCs) derived from dermal fibroblasts of a CFC syndrome patient (CFC-iPSCs) revealed early developmental defects in embryoid body (EB) development, β-catenin localization, and neuronal differentiation. Both SMAD1 and ERK signalings were significantly activated in CFC-iPSCs during EB formation. Most of the β-catenin was dissociated from the membrane and preferentially localized into the nucleus in CFC-EBs. Furthermore, activation of SMAD1 signaling recapitulated early developmental defects in wild-type iPSCs. Intriguingly, inhibition of SMAD1 signaling in CFC-iPSCs rescued aberrant EB morphology, impaired neuronal differentiation, and altered β-catenin localization. These results suggest that SMAD1 signaling may be a key pathway contributing the pathogenesis of CFC syndrome during early development. Stem Cells 2015;33:1447–1455

Additional file 1. The list of genus and species names contained in NPCARE.

Overconsumption of sugar-sweetened beverages (SSBs) is known to be a key contributor to the obesity epidemic; however, its effects on behavioral changes are yet to be fully studied. In the present study, we examined the long-term effects of SSB on social aggression in mice. Three-week-old weaned mice started to drink either a 30 w/v% sucrose solution (S30), plain water (CT), or an aspartame solution with sweetness equivalent to the sucrose solution (A30) and continued to drink until they were 11-week-old adults. Aggressive behaviors were assessed by the resident-intruder test. We found that SSB significantly promoted social aggression, accompanied by heightened serum corticosterone and reduced body weight. To understand the underlying mechanism, we performed transcriptome analyses of brain. The profiles of mice on S30 were dramatically different from those on CT or A30. Transcriptional networks related to immunological function were significantly dysregulated by SSB. FACS analysis of mice on S30 revealed increased numbers of inflammatory cells in peripheral blood. Interestingly, the artificial sweetener failed to mimic the effects of sugar on social aggression and inflammatory responses. These results demonstrate that SSB promotes aggressive behaviors and provide evidence that sugar reduction strategies may be useful in efforts to prevent social aggression.

Background To compare the ceiling effect of the Lysholm and IKDC subjective scores for assessing functional outcome after ACL reconstruction and evaluated the correlation with the one-leg hop test. Methods A total of 134 patients who underwent ACL reconstruction between 2007 and 2011 were enrolled in this study. All patients fulfilled the postoperative 6- and 12-month evaluations. The ceiling effect of the Lysholm and IKDC subjective scores was assessed, and the correlations between two scales and one-leg hop test were analysed. Results For the entire sample, the ceiling effect for the Lysholm score was 14.9% and 30.6% at 6 and 12months postoperatively. The values for the IKDC subjective score were 5.2% and 17.2%, respectively. In all subjects, the correlation coefficients [95% confidence intervals] between the IKDC subjective score and one-leg hop test at 6 and 12months ( r =0.492, [0.34 to 0.62]; r =0.296, [0.12 to 0.46]) were higher than those for the Lysholm score ( r =0.355, [0.18 to 0.51]; r =0.241, [0.06 to 0.41]), respectively.( p Conclusion With regard to evaluating ACL reconstruction outcomes in patients, no significant difference between the IKDC subjective and the Lysholm scores exists in terms of the amount of ceiling effect and the correlation with the LSI. However, the concern that the ceiling effect of the Lysholm score was greater than the IKDC subjective score, should be addressed in assessing the patient's functional status postoperatively. Level of evidence: III, retrospective comparative study.

Aims To examine whether adulthood and/or childhood sex-specific socio-economic disparities are associated with metabolic syndrome and its components in a developed non-Western setting. Methods Based on the Fourth Korea National Health and Nutrition Examination Surveys, 14 888 people aged ≥ 20 years were analysed to evaluate the effect of adult and childhood socio-economic status on metabolic syndrome. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Logistic regression analyses were conducted to calculate the odds ratios for metabolic syndrome and each component of metabolic syndrome in later life. Results The age-standardized prevalence of metabolic syndrome was 26.6% for men and 21.3% for women. Compared with the highest level of education, men with the lowest education level were significantly less likely to have metabolic syndrome (odds ratio 0.76, 95% CI 0.60–0.96), whereas the opposite association was found in women (odds ratio 3.29, 95% CI 2.45–4.42). Men who were manual labourers and economically inactive had a lower prevalence of metabolic syndrome compared with those with non-manual jobs (odds ratio 0.82, 95% CI 0.69–0.98 and odds ratio 0.79, 95% CI 0.64–0.99, respectively), but the reverse association was observed in women (odds ratio 1.34, 95% CI 1.04–1.73 and odds ratio 1.40, 95% CI 1.09–1.81, respectively). A significant interaction between combined adulthood and childhood socio-economic status on the presence of metabolic syndrome was observed (P

Background The quality of life (QoL) of adults with congenital heart disease (CHD) has gained significant interest. In addition to medical problems, many patients with CHD face psychosocial, educational, and behavioral challenges. However, few studies have examined the relationship between disease severity and QoL in adults with CHD. Methods Eighty-five patients (50 men, 35 women) aged 20–52years (median, 26.5years) were enrolled. Patients underwent a QoL, Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) survey. The scores were compared with those of age- and gender-matched population data according to the degree of underlying CHD. Disease severity was classified in relation to initial diagnosis, illness course, and current functional status (New York Heart Association [NYHA] class, ability index, CHD functional index, ventricular ejection fraction, and peak VO 2 ). Results There was no significant correlation between disease severity and current functional status assessed by BDI and BAI. Patients who stated that they were religious had better scores for resilience (p=0.031), physical QoL (p=0.008), and environmental QoL (p=0.025). Environmental QoL scores were higher in patients who fully understood their disease (p=0.004). Current NYHA functional class was associated with scores for psychological resilience. Conclusions CHD severity had a detrimental impact on resilience only when measured in terms of poor functional status. The initial diagnosis and course of the illness influence QoL and perceived health. Good psychosocial adaptation could be the result of close family relationships and involvement, making mental adjustment easier.

Extrinsic airway compression often complicates the course of congenital heart disease (CHD) repair. This study investigated the risk factors and outcome of airway compression evaluated using computed tomography (CT) in CHD patients.Of the 2,729 patients who underwent heart surgery for CHD between 1999 and 2007, airway compression was confirmed using CT in 58 (2.1%) patients. The patients were divided into groups according to the underlying CHD, and their medical records and CT scans were reviewed retrospectively.Airway compression was found more frequently in the vascular ring or absent pulmonary valve syndrome (8 of 11) and repaired aortic arch (22 of 213) groups than in the other groups (28 of 2,505) (p0.001). Patients with more severe respiratory manifestations showed greater airway compression on CT (p0.001) and had a higher rate of additional surgery to relieve airway compression using multivariate analysis (p = 0.005). Airway compression was ameliorated in 13 of 17 patients after surgery for airway compression. Funnel chest deformity worsened after aortic arch repair and was associated with the need for surgical relief of airway compression. Pulmonary overflow disease could be followed up without additional surgery for airway compression.Early airway compression detection and management may reduce further morbidity, especially after aortic arch repair. The patient's respiratory manifestation and the underlying disease characteristics must be considered when determining the need for additional surgery for airway compression.

Background The safety and effectiveness of radiofrequency catheter ablation (RFCA) for supraventricular tachycardia (SVT) in young children was investigated. Methods Ninety-five children who underwent RFCA procedures were stratified according to age (group 1, 0–4 years, n = 24; group 2, 5–9 years, n = 71) and were evaluated retrospectively. Results Among the 95 patients, atrioventricular reentrant tachycardia was 78.9%, atrioventricular nodal reentrant tachycardia was 10.5%, and ectopic atrial tachycardia was 8.4%. The acute success rate of RFCA was 97.9% and the recurrence rate was 11.6%. RFCA was performed for different main reasons in each group, including drug-resistant tachycardia (37.5% in group 1 vs 7% in group 2; P = 0.001) and symptomatic tachycardia (4.2% in group 1 vs 57.7% in group 2; P < 0.001). There was no significant difference in success rate, recurrence rate, and procedure and fluoroscopy duration between the two groups. The acute success rates did not differ significantly between patients with a single accessory pathway (AP) and those with multiple APs; however, failure or recurrence was more common in the patients with multiple APs (38.5% vs 11.5%; P = 0.01). The multiple APs were found frequently on the right side (P = 0.005). Septal dyskinesia with left ventricular dysfunction in Wolff-Parkinson-White syndrome and tachycardia-induced cardiomyopathy improved after RFCA. Conclusions RFCA was found to be effective and safe for SVT in young children.