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This is a copy of the slides presented at the meeting but not formally written up for the volume.
Nanoparticles (NPs) are showing great promise in their utility towards biomedical applications in areas such as drug delivery, diagnostics and image contrast enhancement. The standardization of physical characterization protocols for NPs is critical for their eventual approval and use in clinical settings, and for the development of reliable nanosize reference materials. Field-flow fractionation (FFF) is emerging as a powerful tool to obtain information on the composition, size, and molecular weight of fractionated NP solutions. FFF is classified into several sub-techniques based on the applied "field", with the most common and broadly applicable being asymmetric-flow (A-FFF). A-FFF separates constituents according to their hydrodynamic size, and can be coupled with various detectors, such as UV-Vis, multi-angle light scattering (MALS), differential refractive index (DRI), photon correlation spectroscopy (PCS), fluorescence, and, more recently, inductively coupled plasma-mass spectrometry (ICP-MS). Depending on the different detector systems employed, further information such as the number and distribution of ligands or drug molecules attached to a multifunctional nanomaterial and the frequency of dimer, trimer and higher order aggregates can be obtained.In the present work we have employed commercial A-FFF systems customized with various detectors, including MALS, PCS, DRI and UV-Vis, to establish fundamental protocols for the characterization of gold nanoparticles and their bio- or dendridic-conjugates. These protocols are being applied in the development of new gold-based nanosize reference materials intended for the cancer research community. We optimized the experimental conditions by controlling various parameters, such carrier composition, membrane material, and ratios of channel-to-cross flow rates. Also, samples were separated by collection mode from A-FFF, to coincide with the MALS signal, and subsequently investigated for purity and accuracy by further supportive analysis of off-line UV-Vis and PCS measurements. We report on the results of these studies and their implications for biomedical research.NCL is funded by NCI Contract N01-CO-12400.
Jet-like surface waves generated by an electric-spark-generated underwater bubble are experimentally studied. Three different motions of jet-like surface waves are observed depending on the inception position of the bubble (
: 0.28–7 mm) below the free surface and the maximum radius of the bubble (
: 1.5–3.6 mm). When
, the surface wave shows a simple smooth hump (case 1). When
, a single droplet or multiple droplets are pinched off sequentially or simultaneously at the tip or from some points of the jet-like surface wave (case 2). Finally, when
, a series of squirting and jetting phenomena are observed at the top of the jet-like surface wave (case 3). For case 1, a proportional relationship is found between
is the density of the fluid,
is the gravitational acceleration and
is the difference between the reference atmospheric pressure and the vapour pressure inside a bubble. This proportional relationship is explained semi-analytically using a scaling argument and conservation of momentum and energy, with the help of the Kelvin impulse theory. In addition, we solve the relevant axisymmetric Cauchy–Poisson problem where the initial condition is a jet-like surface wave near its maximum height. By comparing the analytical wave solution with the observed surface wave pattern, it is found that the resultant surface waves are indeed gravity–capillary waves where both the gravity and the surface tension are equally important.
In this study, an improved fluid–structure interaction (FSI) analysis method is developed for a flapping wing. A co-rotational (CR) shell element is developed for its structural analysis. Further, a relevant non-linear dynamic formulation is developed based on the CR framework. Three-dimensional preconditioned Navier–Stokes equations are employed for its fluid analysis. An implicit coupling scheme is employed to combine the structural and fluid analyses. An explicit investigation of a 3D plunging wing is conducted using this FSI analysis method. A further investigation of this plunging wing is performed in relation to its operating condition. In addition, the relation between the wing’s aerodynamic performance and plunging motion is investigated.
The present study aimed to compare the anti-biofilm activities of four commonly available antiseptic eardrops against biofilms from methicillin-resistant Staphylococcus aureus and quinolone-resistant Pseudomonas aeruginosa in vitro.
The anti-biofilm activities of 50 per cent Burow's solution, vinegar with water (1:1), 2 per cent acetic acid solution, and 4 per cent boric acid solution were evaluated using biofilm assays. Additionally, the anti-biofilm activities of the four antiseptic solutions against tympanostomy tube biofilms were compared using a scanning electron microscope.
The inhibition of biofilm formation from methicillin-resistant S aureus and quinolone-resistant P aeruginosa occurred after treatment with 4 per cent boric acid solution, 2 per cent acetic acid solution, and vinegar with water (1:1). However, 50 per cent Burow's solution did not exhibit effective anti-biofilm activity.
The results indicate that 4 per cent boric acid solution and vinegar with water (1:1) are potent inhibitors of biofilms from methicillin-resistant S aureus and quinolone-resistant P aeruginosa, and provide safe pH levels for avoiding ototoxicity.
Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.
Human bocaviruses (HBoVs) have been detected in human gastrointestinal infections worldwide. In 2005, HBoV was also discovered in infants and children with infections of the lower respiratory tract. Recently, several genotypes of this parvovirus, including HBoV genotype 2 (HBoV2), genotype 3 (HBoV3) and genotype 4 (HBoV4), were discovered and found to be closely related to HBoV. HBoV2 was first detected in stool samples from children in Pakistan, followed by detection in other countries. HBoV3 was detected in Australia and HBoV4 was identified in stool samples from Nigeria, Tunisia and the USA. Recently, HBoV infection has been on the rise throughout the world, particularly in countries neighbouring South Korea; however, there have been very few studies on Korean strains. In this study, we characterised the whole genome and determined the phylogenetic position of CUK-BC20, a new clinical HBoV strain isolated in South Korea. The CUK-BC20 genome of 5184 nucleotides (nt) contains three open-reading frames (ORFs). The genotype of CUK-BC20 is HBoV2, and 98.77% of its nt sequence is identical with those of other HBoVs, namely Rus-Nsc10-N386. Especially, the ORF3 amino acid sequences from positions 212–213 and 454 corresponding to a variable region (VR)1 and VR5, respectively, showed genotype-specific substitutions that distinguished the four HBoV genotypes. As the first whole-genome sequence analysis of HBoV in South Korea, this information will provide a valuable reference for the detection of recombination, tracking of epidemics and development of diagnosis methods for HBoV.
Intercalated and unmodified TiS2 nanomaterials were synthesized and characterized by UV-Visible-NIR spectroscopy, Powder X-Ray Diffraction, and X-Ray Photoelectron and Ultraviolet Photoelectron Spectroscopy. Photoelectron spectroscopy measurements indicated that CoS and Cu2S appeared to be intercalated between sheets of partially or fully oxidized TiS2, which could be solution processed on conductive oxide substrates. The materials were then applied toward water oxidation and evaluated by cyclic voltammetry, chronoamperometry, and impedance measurements. While unmodified TiS2 was not observed to perform well as an electrocatalyst with overpotentials >3 V in 1 M NaOH electrolyte, CoS intercalation was found to lower the overpotential by ∼1.8–1.44 V at 10 mA/cm2. Conversely, Cu2S intercalation resulted in only a modest increase in performance (>2.3 V overpotential). Impedance measurements indicated that intercalation increased the series resistance in the as-prepared samples but decreased the series resistance in oxidized samples.
We report on the astrometric registration of VLBI images of the SiO and H2O masers in OH 231.8+4.2, the iconic Proto-Planetary Nebula also known as the Calabash nebula, using the KVN and Source/Frequency Phase Referencing. This, for the first time, robustly confirms the alignment of the SiO masers, close to the AGB star, which drives the bi-lobe structure with the water masers in the out-flow.
We estimated the heritabilities (h2) and genetic and phenotypic correlations among individual and groups of fatty acids, as well as their correlations with six important carcass and meat-quality traits in Korean Hanwoo cattle. Meat samples were collected from the longissimus dorsi muscles of 1000 Hanwoo steers that were 30-month-old (progeny of 85 proven Hanwoo bulls) to determine intramuscular fatty acid profiles. Phenotypic data on carcass weight (CWT), eye muscle area (EMA), back fat thickness (BFT), marbling score (MS), Warner–Bratzler shear force (WBSF) and intramuscular fat content (IMF) were also investigated using this half-sib population. Variance and covari.ance components were estimated using restricted maximum likelihood procedures under univariate and pairwise bivariate animal models. Oleic acid (C18:1n-9) was the most abundant fatty acid, accounting for 50.69% of all investigated fatty acids, followed by palmitic (C16:0; 27.33%) and stearic acid (C18:0; 10.96%). The contents of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) were 41.64%, 56.24% and 2.10%, respectively, and the MUFA/SFA ratio, PUFA/SFA ratio, desaturation index (DI) and elongation index (EI) were 1.36, 0.05, 0.59 and 0.66, respectively. The h2 estimates for individual fatty acids ranged from very low to high (0.03±0.14 to 0.63±0.14). The h2 estimates for SFAs, MUFAs, PUFAs, DI and EI were 0.53±0.14, 0.49±0.14, 0.23±0.10, 0.51±0.13 and 0.53±0.13, respectively. The genetic and phenotypic correlations among individual fatty acids and fatty acid classes varied widely (−0.99 to 0.99). Notably, C18:1n-9 had favourable (negative) genetic correlations with two detrimental fatty acids, C14:0 (−0.76) and C16:0 (−0.92). Genetic correlations of individual and group fatty acids with CWT, EMA, BFT, MS, WBSF and IMF ranged from low to moderate (both positive and negative) with the exception of low-concentration PUFAs. Low or near-zero phenotypic correlations reflected potential non-genetic contributions. This study provides insights on genetic variability and correlations among intramuscular fatty acids as well as correlations between fatty acids and carcass and meat-quality traits, which could be used in Hanwoo breeding programmes to improve fatty acid compositions in meat.
Noroviruses (NoVs) are major causal agents of acute gastroenteritis in humans. NoV GII.4 is the predominant genotype globally. However, uncommon and minor types of NoVs are consistently detected and some have been shown to dominate over GII.4. Therefore, the prevalence of dominant and uncommon NoVs makes the identification of these viruses important for the prediction and prevention of pandemics. In this study, the full-genome sequence of a NoV (strain JW) detected in Korea was extensively characterized. The full-length genome was 7510 nucleotides long, and phylogenetic analysis based on the whole-genome sequences, including open reading frame (ORF)1, ORF2, and ORF3, indicated that it belonged to the GII.21 genotype. Strain JW showed maximum identity with strain YO284; however, comparison of the amino acid sequence of ORF2, which functions as an antigen, showed substitutions in several amino acids. GII.21 is not a prevalent epidemiological agent of acute gastroenteritis in humans, but it is consistently found in gastroenteritis patients from several countries. The present study provides the first full-genome sequence analysis of NoV GII.21 isolated from a patient in Korea. Our findings provide not only valuable genome information but also data for epidemiology studies, epidemic prevention, and vaccine development strategies.
In South Korea, the resurgence of mumps was noted primarily among school-aged children and adolescents since 2000. We analyzed spatial patterns in mumps incidence to give an indication to the geographical risk. We used National Notifiable Disease Surveillance System data from 2001 to 2015, classifying into three periods according to the level of endemicity. A geographic-weighted regression analysis was performed to find demographic predictors of mumps incidence according to district level. We assessed the association between the total population size, population density, percentage of children (age 0–19 years), timely vaccination rate of measles–mumps–rubella vaccines and the higher incidence rate of mumps. During low endemic periods, there were sporadic regional distributions of outbreak in the central and northern part of the country. During intermediate endemic periods, the increase of incidence was noted across the country. During high endemic period, a nationwide high incidence of mumps was noted especially concentrated in southwestern regions. A clear pattern for the mumps cluster shown through global spatial autocorrelation analysis from 2004 to 2015. The ‘non-timely vaccination coverage’ (P = 0·002), and ‘proportion of children population’ (P < 0·001) were the predictors for high mumps incidence in district levels. Our study indicates that the rate of mumps incidence according to geographic regions vary by population proportion and neighboring regions, and timeliness of vaccination, suggesting the importance of community-level surveillance and improving of timely vaccination.
In a family of Sd+1-fields (d = 2, 3, 4), we obtain the conjectured upper and lower bounds of the residues of Dedekind zeta functions except for a density zero set. For S5-fields, we need to assume the strong Artin conjecture. We also show that there exists an infinite family of number fields with the upper and lower bounds, resp.
High-grade gliomas are deadly cancers, and current standard-of-care has demonstrated limited success. The ability to specifically target glioma cells can allow for the development of improved theranostic agents leading to better detection methods, as well as safer anti-cancer therapies. Brevican (Bcan), a CNS-specific protein is upregulated in glioma cells and correlates with tumor progression. Particularly, a Bcan isoform lacking normal glycosylation, called B/bDg is a unique glioma marker and is not expressed in non-cancerous tissues. Therefore, B/bDg represents a valuable target for anti-cancer strategies. We describe here the discovery of novel high-affinity B/bDg-targeted peptides using rapid combinatorial library screening approaches and a microfluidic sorting device of our own design. Briefly, a one-bead-one-compound (OBOC) peptide library was screened against small magnetic particles decorated with B/bDg. Positive “hit” beads labeled with magnetic particles were isolated using an inexpensive but yet, accurate and high-throughput in-house microfluidic magnetic-activated sorter. These hits were exposed to cells expressing B/bDg, and beads with the highest cell association were isolated and sequenced. Seven novel peptides were identified. Cell uptake analyses and blocking studies revealed that 5 of these peptides displayed specific uptake in B/bDg-overexpressing cells. These candidates displayed nano-/micromolar binding affinity for recombinant B/bDg protein. Further analyses of these candidates using confocal microscopy revealed increased peptide binding/uptake in patient-derived glioma stem cells (GSCs) compared with primary human astrocytes. We plan to incorporate these onto multi-functional BBB-penetrating nanoparticles loaded with imaging agents or a drug payload to translate them into highly selective and efficacious brain cancer theranostic agents.
Sparganosis is one of the top three tissue-dwelling heterologous helminthic diseases, along with cysticercosis and paragonimiasis, in Korea. Due to a lack of effective early diagnosis and treatment methods, this parasitic disease is regarded as a public health threat. This study evaluated reactivity, against sparganum extracts, of sera from inhabitants of Cheorwon-gun, Goseong-gun and Ongjin-gun in Korea. The sera from 836 subjects were subjected to enzyme-linked immunosorbent assay and immunoblot analysis. The sera from 18 (5.8%) and 15 (5.1%) inhabitants in Cheorwon-gun (n = 312) and Goseong-gun (n = 294), respectively, exhibited highly positive reactions to the sparganum antigen, whereas only two (0.9%) inhabitants in Ongjin-gun (n = 230) showed positivity. We sought antigenic proteins for serodiagnosis of positive sera by immunoproteomic approaches. Total sparganum lysates were separated by two-dimensional electrophoresis and then subjected to immunoblot analysis with mixed sparganosis-positive sera. We found seven antigenic spots and identified paramyosin as an antigenic protein by liquid chromatography–mass spectrometry. By two-dimensional (2D)-based mass analysis and immunoblotting against sparganosis-positive sera, paramyosin was identified as a candidate antigen for serodiagnosis of sparganosis.
Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia.
A total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids. They were also compared using a 75 g oral glucose tolerance test and the homeostasis model assessment of insulin resistance (HOMA-IR). Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).
Of the patients, 24.5% had IGT compared with none of the controls, and they also had significantly higher levels of fasting blood glucose and 2-h glucose after an oral glucose load, and were more insulin resistant. Compared with those patients with normal glucose tolerance, the IGT patients were older, had a later age of onset, higher waist or hip circumference and body mass index, higher levels of low-density lipoprotein and triglycerides and higher insulin resistance. Furthermore, IGT patients had higher PANSS total and negative symptom subscale scores, but no greater cognitive impairment except on the emotional intelligence index of the MCCB.
IGT occurs with greater frequency in FEDN schizophrenia, and shows association with demographic and anthropometric parameters, as well as with clinical symptoms but minimally with cognitive impairment during the early course of the disorder.
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.
Necrotising enterocolitis (NEC) is an uncommon, but devastating intestinal inflammatory disease that predominantly affects preterm infants. NEC is sometimes dubbed the spectre of neonatal intensive care units, as its onset is insidiously non-specific, and once the disease manifests, the damage inflicted on the baby's intestine is already disastrous. Subsequent sepsis and multi-organ failure entail a mortality of up to 65%. Development of effective treatments for NEC has stagnated, largely because of our lack of understanding of NEC pathogenesis. It is clear, however, that NEC is driven by a profoundly dysregulated immune system. NEC is associated with local increases in pro-inflammatory mediators, e.g. Toll-like receptor (TLR) 4, nuclear factor-κB, tumour necrosis factor, platelet-activating factor (PAF), interleukin (IL)-18, interferon-gamma, IL-6, IL-8 and IL-1β. Deficiencies in counter-regulatory mechanisms, including IL-1 receptor antagonist (IL-1Ra), TLR9, PAF-acetylhydrolase, transforming growth factor beta (TGF-β)1&2, IL-10 and regulatory T cells likely facilitate a pro-inflammatory milieu in the NEC-afflicted intestine. There is insufficient evidence to conclude a predominance of an adaptive Th1-, Th2- or Th17-response in the disease. Our understanding of the accompanying regulation of systemic immunity remains poor; however, IL-1Ra, IL-6, IL-8 and TGF-β1 show promise as biomarkers. Here, we chart the emerging immunological landscape that underpins NEC by reviewing the involvement and potential clinical implications of innate and adaptive immune mediators and their regulation in NEC.