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The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The asymptotic phase θ of an initial point x in the stable manifold of a limit cycle (LC) identifies the phase of the point on the LC to which the flow φt(x) converges as t → ∞. The infinitesimal phase response curve (iPRC) quantifies the change in timing due to a small perturbation of a LC trajectory. For a stable LC in a smooth dynamical system, the iPRC is the gradient ∇x(θ) of the phase function, which can be obtained via the adjoint of the variational equation. For systems with discontinuous dynamics, the standard approach to obtaining the iPRC fails. We derive a formula for the iPRCs of LCs occurring in piecewise smooth (Filippov) dynamical systems of arbitrary dimension, subject to a transverse flow condition. Discontinuous jumps in the iPRC can occur at the boundaries separating subdomains, and are captured by a linear matching condition. The matching matrix, M, can be derived from the saltation matrix arising in the associated variational problem. For the special case of linear dynamics away from switching boundaries, we obtain an explicit expression for the iPRC. We present examples from cell biology (Glass networks) and neuroscience (central pattern generator models). We apply the iPRCs obtained to study synchronization and phase-locking in piecewise smooth LC systems in which synchronization arises solely due to the crossing of switching manifolds.
Fluid–structure interactions are ubiquitous in nature and technology. However, the systems are often so complex that numerical simulations or ad hoc assumptions must be used to gain insight into the details of the complex interactions between the fluid and solid mechanics. In this paper, we present experiments and theory on viscous flow in a simple bioinspired soft valve which illustrate essential features of interactions between hydrodynamic and elastic forces at low Reynolds numbers. The set-up comprises a sphere connected to a spring located inside a tapering cylindrical channel. The spring is aligned with the central axis of the channel and a pressure drop is applied across the sphere, thus forcing the liquid through the narrow gap between the sphere and the channel walls. The sphere’s equilibrium position is determined by a balance between spring and hydrodynamic forces. Since the gap thickness changes with the sphere’s position, the system has a pressure-dependent hydraulic resistance. This leads to a nonlinear relation between applied pressure and flow rate: flow initially increases with pressure, but decreases when the pressure exceeds a certain critical value as the gap closes. To rationalize these observations, we propose a mathematical model that reduced the complexity of the flow to a two-dimensional lubrication approximation. A closed-form expression for the pressure drop/flow rate is obtained which reveals that the flow rate
depends on the pressure drop
, sphere radius
, gap thickness
, and viscosity
, where the critical pressure
scales with the spring constant
. These predictions compared favourably to the results of our experiments with no free parameters.
Respiratory syncytial virus (RSV) can cause serious respiratory infections, second only to influenza virus. In order to know RSV's genetic changes we examined 4028 respiratory specimens from local hospital outpatients in Gyeonggi Province, South Korea over six consecutive years by real-time one-step RT–PCR; 183 patients were positive for RSV infection. To investigate the specific distribution of RSV genotypes, we performed partial sequencing of the glycoprotein gene. Of the 131 RSV-A specimens sequenced, 61 (43·3%) belonged to the ON1 genotype, 66 (46·8%) were NA1 genotype, 3 (2·1%) were GA5 genotype, and 1 (0·7%) belonged to the GA1 genotype. Of the 31 RSV-B specimens sequenced, 29 were BA9 genotype (87·9%) and 2 were BA10 genotype (6·1%). The most common clinical symptoms were fever, cough, nasal discharge, and phlegm; multiple logistic regression analysis showed that RSV-positive infection on pediatric patients was strongly associated with cough (OR = 2·8, 95% CI 1·6–5·1) and wheezing (OR = 2·8, 95% CI 1·7–4·4). The ON1 genotype was significantly associated with phlegm (OR = 11·8, 95% CI 3·8–46·7), while the NA1 genotype was associated with the pediatric patients’ gender (males, OR = 2·4, 95% CI 1·1–5·4) and presence of chills (OR = 5·1, 95% CI 1·1–27·2). RSV subgroup B was showed association with nasal obstruction (OR = 4·6, 95% CI 1·2–20·0). The majority of respiratory virus coinfections with RSV were human rhinovirus (47·2%). This study contributes to our understanding of the molecular epidemiological characteristics of RSV, which promotes the potential for improving RSV vaccines.
A radiocarbon (14C) dating technique with accelerator mass spectrometry (AMS) was applied to estimate the year of death and the year of birth of unidentified human remains. Because many of the samples have been preserved in formaldehyde, it was necessary to evaluate the influence of formaldehyde on carbon ages. Samples intentionally preserved in formaldehyde during the known period were measured, and their Δ14C values were compared with results obtained from fresh samples. The influence of formaldehyde on soft tissue was 14 times larger than that on cortical bone. Unfortunately, an effective method for removing the influence of formaldehyde has not yet been found. 14C ages could be obtained only from the samples not preserved in formaldehyde. The years of birth were determined by the ages of the dentin samples, while the years of death were determined by the ages of the bone and soft tissue samples. Multiple sampling from a body provides an advantage in determination of one of two possible ages of a sample obtained using the bomb peak. Victims of the Korean War were ascertained by the year of death. The year of death and the age at death of unidentified bodies were also determined for forensic investigation.
Extended-spectrum β-lactamase (ESBL) production has been very rare in serotype K1 Klebsiella pneumoniae ST23 strains, which are well-known invasive community strains. Among 92 ESBL-producing strains identified in 218 isolates from nine Asian countries, serotype K1 K. pneumoniae strains were screened. Two ESBL-producing K. pneumoniae isolates from Singapore and Indonesia were determined to be serotype K1 and ST23. Their plasmids, which contain CTX-M-15 genes, are transferable rendering the effective transfer of ESBL resistance plasmids to other organisms.
The relationship between temperature and time required for collagenization using modern bone samples was investigated. Gelatinized samples of bone collagen were filtered to selectively collect different molecular weight fractions. The results of this study suggest that heating to 70 ° for a duration of 12 hr provides the optimal conditions for gelatinization.
We have observed A14C concentrations in the northern hemisphere temperate region in the bomb pulse period, using cross-dated tree ring samples. The tree-ring samples were taken from one 70-year-old and two 50-year-old red pines (Pinus densiflora) on Mt Chiak, Korea and from a 50-year-old red pine (Pinus densiflora) on Mt Kyeryong, Korea. Twenty-two tree-ring samples from four red pines ranging from 1950 to 2000 AD were pretreated to obtain holo-cellulose, combusted to CO2 by an element analyzer (EA) and converted to graphite for δ14C measurement using the accelerator mass spectrometry (AMS) facility at Seoul National University. Our results for δ14C showed good agreement with those measured by other researchers at similar latitudes. The observed steady decrease of δ14C from 1965 to 2000 AD is described by a single exponential function with a lifetime τ = 15.99 ± 0.43 yr. This lifetime is similar to that of the high-latitude region in Europe.
The development of radiocarbon dating for degraded bone samples collected at Korean archaeological sites has been successful through the characterization of raw bone C/N ratios and application of an ultrafiltration method. It was found that the C/N ratios of raw bone samples are inversely proportional to the carbon content and residue amount after gelatinization. We have examined a few dozen Korean archaeological bone samples for this study. Well-preserved bone samples are found to be physically dense. The range of C/N ratios of Korean raw bone samples ranged from 3.4 to 74. We found that the C/N ratios of degraded raw bone samples can be used to determine whether 14C samples are acceptable for normal pretreatment processing and eventual dating. The results of this study support that even if the C/N ratio of a degraded raw bone sample is 11, extraction of collagen for bone dating is feasible by a carefully designed ultrafiltration process. Our preliminary 14C dating results of a depth profile of Gunang-gul Cave, an archaeological site in Danyang, Korea, indicate that this site has been either geologically or anthropologically disturbed in the past, with 14C ages ranging from 28,910 ± 200 to 48,090 ± 1050 yr BP. The C/N ratios of the collagen samples of Gunang-gul were determined to be 3.2–3.6. Our study establishes a new guide for the pretreatment of degraded bone samples such as those collected in Korea for 14C dating.
The accelerator mass spectrometry facility at the Seoul National University (SNU-AMS) was completed in December 1998 and a report was presented at the Vienna AMS conference in September 1999. At the conference, we described the basic components of our accelerator system and reported the results of the performance test. Since then, extensive testing of the accuracy and reproducibility of the system has been carried out, and about 200 unknown samples have been measured so far. We obtained a precision of 4‰ for modern samples, and an accuracy of approximately 40 yr was demonstrated by analyzing samples that were previously dated with a conventional technique and by other AMS laboratories. We present these results here, together with detailed descriptions of our data-taking and analysis procedures.
The accelerator mass spectrometry facility at Seoul National University (SNU-AMS) began functioning in December 1998 and was first reported at the Vienna AMS conference in October 1999 and at the 17th International Radiocarbon Conference in Israel in June 2000. At the Vienna conference, we reported our accelerator system (Kim et al. 2000) and details of the basic sample preparation system (Lee et al. 2000), such as the combustion line to produce CO2; the catalytic reduction line for the graphitization of CO2; and the pretreatment procedures for wood, charcoal, and peat samples. The recent progress of the AMS facility (Kim et al. 2001) and the extension of the sample pretreatment system to iron and bone samples were reported at the 17th International Radiocarbon Conference (Cheoun et al. 2001). In the meantime, extensive testing of accuracy and reproducibility has been carried out, and ∼1000 unknown archaeological and geological samples have been measured every year. In this report, the archaeological, geological, and environmental data carried out in 1999 are presented in terms of yr BP.
The accelerator mass spectrometry facility at Seoul National University (SNU-AMS) began functioning in December 1998 and was first reported at the Vienna AMS conference in October 1999 and at the 17th Radiocarbon Conference in Israel in June 2000. At the Vienna conference, we reported our accelerator system (Kim et al. 2000) and the basic sample preparation system (Lee et al. 2000), including the combustion line to produce CO2; the catalytic reduction line for the graphitization of CO2; and also pretreatment procedures for wood, charcoal, and peat samples. Recent progress of the AMS facility (Kim et al. 2001) and extension of the sample pretreatment system to iron and bone samples were reported at the 17th Radiocarbon Conference (Cheoun et al. 2001). In the meantime, extensive testing of accuracy and reproducibility has been carried out, and ∼1000 unknown archaeological and geological samples have been measured every year. A report of data carried out in 1999 is presented by Kim et al. (this issue). In this report, the archaeological, geological, and environmental data carried out in 2000 are presented in terms of yr BP.
We present the current status of accelerator mass spectrometry (AMS) dating of iron artifacts at Seoul National University (SNU). In ancient iron production, charcoal was widely used as carbon for the smelting process, whereas coal is used in modern times. If reliable data could be obtained from carbon by using AMS, ancient iron artifacts could be traced to their production age. In normal acid treatment, it is not easy to extract carbon due to its colloidal property. The negative charge property of the carbon colloid, however, makes it possible for it to be precipitated with positive ions by dissolving the iron chemically. An extraction yield of the carbon incorporated in modern cast iron of about 70% is attained. More refined methods to increase the extraction rate are under progress for archaeological applications.
We present recent observation results of Sgr A* at millimeter obtained with VLBI arrays in Korea and Japan.
7 mm monitoring of Sgr A* is part of our AGN large project. The results at 7 epochs during 2013-2014, including high resolution maps, flux density and two-dimensional size measurements are presented. The source shows no significant variation in flux and structure related to the G2 encounter in 2014. According to recent MHD simulations by kawashima et al., flux and magnetic field energy can be expected to increase several years after the encounter; We will keep our monitoring in order to test this prediction.
Astrometric observations of Sgr A* were performed in 2015 at 7 and 3.5 millimeter simultaneously. Source-frequency phase referencing was applied and a combined ”core-shift” of Sgr A* and a nearby calibrator was measured. Future observations and analysis are necessary to determine the core-shift in each source.
Δ14C values of leaves of deciduous trees provide a means to map the regional-scale fossil fuel ratio in the atmosphere. We collected a batch of ginkgo (Ginkgo biloba Linnaeus, a deciduous tree) leaf samples from across Korea in the month of July in both 2010 and 2011 to obtain the regional distribution of Δ14C. The Δ14C values of the samples were measured using accelerator mass spectrometry (AMS) at the Korea Institute of Geoscience and Mineral Resources (KIGAM). The average of the Δ14C values from clean air sites in Korea in 2011 measured slightly lower than the average of Δ14C values in 2010. Distribution maps of Δ14C of 2011 and 2010 in Korea were made based on a series of Δ14C values of ginkgo leaf samples from Korea using the Geostatistical and Spatial analyst tools in ESRI's ArcMap software. The distribution maps of Δ14C showed that Δ14C values in the western part of Korea are lower than those in the eastern part of Korea. This is because the western part of Korea is densely populated and contains many industrial complexes, and also because westerly winds from China, containing CO2 from fossil fuel use, blow into Korea. We compared the distribution maps of 2010 and 2011 and tried to find traces of the Fukushima power plant accident in Japan.
Various carbon structures, including carbon nanofilament (CNF), single-wall carbon nanotube (SWCNT), multi-wall carbon nanotube (MWCNT), and pyrolytic graphite sheet (PGS), were exposed in air to determine how they vary according to carbon structure and air temperature. CNF is the carbon structure used in accelerator mass spectrometry (AMS) radiocarbon dating (Santos et al. 2007). When CNF and MWCNT were exposed in cold air (3 or −18 °C) for longer than 6 hr, their 14C/12C ratio increased (>5 × 10–14). When heated in an oven (200 or 250 °C) for longer than 12 hr, their 14C/12C ratio decreased. However, when SWCNT and PGS were exposed in air cooled to 3 °C for 12 hr, their 14C/12C ratio did not increase. This phenomenon is very curious, and is useful for the development of a storage method for carbon samples made by reduction reactions of CO2.
This study evaluated whether primary tumour characteristics are associated with specific features of metastatic lymph nodes in papillary thyroid carcinoma patients.
A retrospective review of 411 patients with pathologically diagnosed cervical lymph node metastasis was conducted.
A metastatic lymph node focus size of at least 2 mm was independently associated with a primary tumour size of at least 1 cm (hazard ratio 1.962) and with male sex (hazard ratio 1.947). A number of at least five lymph node metastases was independently associated with a primary tumour size of at least 1 cm (hazard ratio 2.863), extrathyroidal extension (hazard ratio 1.737) and male sex (hazard ratio 1.689). Extranodal extension was independently associated with a primary tumour size of at least 1 cm (hazard ratio 2.288), extrathyroidal extension (2.201) and male sex (hazard ratio 1.733).
Primary papillary thyroid carcinoma characteristics are related to the pathological features of lymph node metastases.
Obsessive–compulsive disorder (OCD) has been associated with abnormal cognitive and emotional functions and these dysfunctions may be dependent on the disruption of dynamic interactions within neuronal circuits associated with emotion regulation. Although several studies have shown the aberrant cognitive–affective processing in OCD patients, little is known about how to characterize effective connectivity of the disrupted neural interactions. In the present study, we applied effective connectivity analysis using dynamic causal modeling to explore the disturbed neural interactions in OCD patients.
A total of 20 patients and 21 matched healthy controls performed a delayed-response working memory task under emotional or non-emotional distraction while undergoing functional magnetic resonance imaging.
During the delay interval under negative emotional distraction, both groups showed similar patterns of activations in the amygdala. However, under negative emotional distraction, the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC) exhibited significant differences between groups. Bayesian model averaging indicated that the connection from the DLPFC to the OFC was negatively modulated by negative emotional distraction in patients, when compared with healthy controls (p < 0.05, Bonferroni-corrected).
Exaggerated recruitment of the DLPFC may induce the reduction of top-down prefrontal control input over the OFC, leading to abnormal cortico-cortical interaction. This disrupted cortico-cortical interaction under negative emotional distraction may be responsible for dysfunctions of cognitive and emotional processing in OCD patients and may be a component of the pathophysiology associated with OCD.