Single quantum dot selection and tailor-made photonic device integration using nanoscale focus pinspot

Among the diverse platforms of quantum light sources, epitaxially grown semiconductor quantum dots (QDs) are one of the most attractive workhorses for realizing various quantum photonic technologies owing to their outstanding brightness and scalability. There exist various material systems for these QDs based on their appropriate emission bandwidth; however, only a few material systems have successfully grown single or low-density QDs, which are essential for quantum light sources. In most other material systems, it is difficult to realize low-density QDs, and the mesa-etching process is usually undergone in order to reduce their density. Nevertheless, the etching process irreversibly destroys the medium near the QD, which is detrimental to in-plane device integration. In this study, we apply a nondestructive luminescence picking method termed as nanoscale focus pinspot (NFP) using helium ion microscopy to reduce the luminous QD density while retaining the surrounding medium. Given that the NFP can precisely manipulate the luminescence at nanoscale resolution, a photonic device can be deterministically fabricated on the target QD matched from both spatial and spectral points of view. After applying the NFP, we extract only a single QD emission out of the high-density ensemble QD emission. Moreover, the photonic structure of a circular Bragg reflector is deterministically integrated with the selected QD, and the extraction efficiency of the QD emission has been improved 27 times. Furthermore, this technique does not destroy the medium and only controls the luminescence. Hence, it is highly applicable to various photonic structures, including photonic waveguides or photonic crystal cavities regardless of their materials.Comment: 16 pages, 5 figure

Genetic Effects of FTO and MC4R Polymorphisms on Body Mass in Constitutional Types

Sasang constitutional medicine (SCM), a Korean tailored medicine, categorizes human beings into four types through states of physiological imbalances and responsiveness to herbal medicine. One SCM type susceptible to obesity seems sensitive to energy intake due to an imbalance toward preserving energy. Common variants of fat mass and obesity associated (FTO) and melanocortin 4 receptor (MC4R) genes have been associated with increased body mass index (BMI) by affecting energy intake. Here, we statistically examined the association of FTO and MC4R polymorphisms with BMI in two populations with 1370 Koreans before and after SCM typing, and with the lowering of BMI in 538 individuals who underwent a 1-month lifestyle intervention. The increased BMI replicated the association with FTO haplotypes (effect size ≃ 1.1 kg/m2) and MC4R variants (effect size ≃ 0.64 kg/m2). After the lifestyle intervention, the carriers of the haplotype represented by the minor allele of rs1075440 had a tendency to lose more waist-to-hip ratio (0.76%) than non-carriers. The constitutional discrepancy for the accumulation of body mass by the effects of FTO and/or MC4R variants seemed to reflect the physique differences shown in each group of SCM constitutional types. In conclusion, FTO and MC4R polymorphisms appear to play an important role in weight gain, while only FTO variants play a role in weight loss after lifestyle intervention. Different trends were observed among individuals of SCM types, especially for weight gain. Therefore, classification of individuals based on physiological imbalance would offer a good genetic stratification system in assessing the effects of obesity genes

Network-assisted protein identification and data interpretation in shotgun proteomics

Protein assembly and biological interpretation of the assembled protein lists are critical steps in shotgun proteomics data analysis. Although most biological functions arise from interactions among proteins, current protein assembly pipelines treat proteins as independent entities. Usually, only individual proteins with strong experimental evidence, that is, confident proteins, are reported, whereas many possible proteins of biological interest are eliminated. We have developed a clique-enrichment approach (CEA) to rescue eliminated proteins by incorporating the relationship among proteins as embedded in a protein interaction network. In several data sets tested, CEA increased protein identification by 8–23% with an estimated accuracy of 85%. Rescued proteins were supported by existing literature or transcriptome profiling studies at similar levels as confident proteins and at a significantly higher level than abandoned ones. Applying CEA on a breast cancer data set, rescued proteins coded by well-known breast cancer genes. In addition, CEA generated a network view of the proteins and helped show the modular organization of proteins that may underpin the molecular mechanisms of the disease

A high-throughput \u3ci\u3ede novo\u3c/i\u3e sequencing approach for shotgun proteomics using high-resolution tandem mass spectrometry

Abstract Background High-resolution tandem mass spectra can now be readily acquired with hybrid instruments, such as LTQ-Orbitrap and LTQ-FT, in high-throughput shotgun proteomics workflows. The improved spectral quality enables more accurate de novo sequencing for identification of post-translational modifications and amino acid polymorphisms. Results In this study, a new de novo sequencing algorithm, called Vonode, has been developed specifically for analysis of such high-resolution tandem mass spectra. To fully exploit the high mass accuracy of these spectra, a unique scoring system is proposed to evaluate sequence tags based primarily on mass accuracy information of fragment ions. Consensus sequence tags were inferred for 11,422 spectra with an average peptide length of 5.5 residues from a total of 40,297 input spectra acquired in a 24-hour proteomics measurement of Rhodopseudomonas palustris. The accuracy of inferred consensus sequence tags was 84%. According to our comparison, the performance of Vonode was shown to be superior to the PepNovo v2.0 algorithm, in terms of the number of de novo sequenced spectra and the sequencing accuracy. Conclusions Here, we improved de novo sequencing performance by developing a new algorithm specifically for high-resolution tandem mass spectral data. The Vonode algorithm is freely available for download at http://compbio.ornl.gov/Vonode webcite

VEGFR2 but not VEGFR3 governs integrity and remodeling of thyroid angiofollicular unit in normal state and during goitrogenesis

Thyroid gland vasculature has a distinguishable characteristic of endothelial fenestrae, a critical component for proper molecular transport. However, the signaling pathway that critically governs the maintenance of thyroid vascular integrity, including endothelial fenestrae, is poorly understood. Here, we found profound and distinct expression of follicular epithelial VEGF-A and vascular VEGFR2 that were precisely regulated by circulating thyrotropin, while there were no meaningful expression of angiopoietin-Tie2 system in the thyroid gland. Our genetic depletion experiments revealed that VEGFR2, but not VEGFR3, is indispensable for maintenance of thyroid vascular integrity. Notably, blockade of VEGF-A or VEGFR2 not only abrogated vascular remodeling but also inhibited follicular hypertrophy, which led to the reduction of thyroid weights during goitrogenesis. Importantly, VEGFR2 blockade alone was sufficient to cause a reduction of endothelial fenestrae with decreases in thyrotropin-responsive genes in goitrogen-fed thyroids. Collectively, these findings establish follicular VEGF-Avascular VEGFR2 axis as a main regulator for thyrotropindependent thyroid angiofollicular remodeling and goitrogenesis.Peer reviewe

Seoul Neuropsychological Screening Battery-Dementia Version (SNSB-D): A Useful Tool for Assessing and Monitoring Cognitive Impairments in Dementia Patients

The Seoul Neuropsychological Screening Battery (SNSB) is one of the standardized neuropsychological test batteries widely used in Korea. However, it may be a bit too lengthy for patients with decreased attention span; and it does not provide the score of global cognitive function (GCF), which is useful for monitoring patients longitudinally. We sought to validate a dementia version of SNSB (SNSB-D) that was shorter than the original SNSB and contained only scorable tests with a GCF score of 300. We administered SNSB-D to patients with mild cognitive impairment (MCI) (n=43) and Alzheimer's disease (AD) (n=93), and normal controls (NC) (n=77). MCI and AD groups had GCF scores significantly different from NC group, and GCF scores were able to distinguish patients with Clinical Dementia Rating of 0.5 and 1. Test-retest reliability was high, with a correlation coefficient of 0.918 for AD, 0.999 for MCI, and 0.960 for NC. The GCF score significantly correlated with the Mini-Mental State Examination (MMSE). Through ROC-curve analysis, GCF scores were found to yield more accurate diagnoses than the MMSE. The SNSB-D is a valid, reliable tool for assessing the overall cognitive function, and can be used to monitor cognitive changes in patients with dementia

Localized Character of 4f Electrons in CeRhx_x(x=2,3) and CeNix_x(x=2,5)

We have measured Ce 4f spectral weights of extremely $\alpha$-like Ce-transition metal intermetallic compounds CeRh$_x$ (x=2,3) and CeNi$_x$ (x=2,5) by using the {\it bulk-sensitive} resonant photoemission technique at the Ce $M_5$($3d_{5/2}\to4f$)-edge. Unprecedentedly high energy resolution and longer escape depth of photoemitted electron at this photon energy enabled us to distinguish the sharp Kondo resonance tails at the Fermi level, which can be well described by the Gunnarsson-Sch\"onhammer(GS) calculation based on the Anderson Impurity Hamiltonian. On the other hand, the itinerant 4f band description shows big discrepancies, which implies that Ce 4f electrons retain localized characters even in extremely $\alpha$-like compounds.Comment: 4 pages, 3 figures, submitted to Phys. Rev. Let

Association between colony-stimulating factor 1 receptor gene polymorphisms and asthma risk

Colony-stimulating factor 1 receptor (CSF1R) is expressed in monocytes/macrophages and dendritic cells. These cells play important roles in the innate immune response, which is regarded as an important aspect of asthma development. Genetic alterations in the CSF1R gene may contribute to the development of asthma. We investigated whether CSF1R gene polymorphisms were associated with the risk of asthma. Through direct DNA sequencing of the CSF1R gene, we identified 28 single nucleotide polymorphisms (SNPs) and genotyped them in 303 normal controls and 498 asthmatic patients. Expression of CSF1R protein and mRNA were measured on CD14-positive monocytes and neutrophils in peripheral blood of asthmatic patients using flow cytometry and real-time PCR. Among the 28 polymorphisms, two intronic polymorphism (+20511C>T and +22693T>C) were associated with the risk of asthma by logistic regression analysis. The frequencies of the minor allele at CSF1R +20511C>T and +22693T>C were higher in asthmatic subjects than in normal controls (4.6 vs. 7.7%, p = 0.001 in co-dominant and dominant models; 16.4 vs. 25.8%, p = 0.0006 in a recessive model). CSF1R mRNA levels in neutrophils of the asthmatic patients having the +22693CC allele were higher than in those having the +22693TT allele (p = 0.026). Asthmatic patients with the +22693CC allele also showed significantly higher CSF1R expression on CD14-positive monocytes and neutrophils than did those with the +22693TT allele (p = 0.045 and p = 0.044). The +20511C>T SNP had no association with CSF1R mRNA or protein expression. In conclusion, the minor allele at CSF1R +22693T>C may have a susceptibility effect in the development of asthma, via increased CSF1R protein and mRNA expression in inflammatory cells

Stroke awareness decreases prehospital delay after acute ischemic stroke in korea

BACKGROUND: Delayed arrival at hospital is one of the major obstacles in enhancing the rate of thrombolysis therapy in patients with acute ischemic stroke. Our study aimed to investigate factors associated with prehospital delay after acute ischemic stroke in Korea. METHODS: A prospective, multicenter study was conducted at 14 tertiary hospitals in Korea from March 2009 to July 2009. We interviewed 500 consecutive patients with acute ischemic stroke who arrived within 48 hours. Univariate and multivariate analyses were performed to evaluate factors influencing prehospital delay. RESULTS: Among the 500 patients (median 67 years, 62% men), the median time interval from symptom onset to arrival was 474 minutes (interquartile range, 170-1313). Early arrival within 3 hours of symptom onset was significantly associated with the following factors: high National Institutes of Health Stroke Scale (NIHSS) score, previous stroke, atrial fibrillation, use of ambulance, knowledge about thrombolysis and awareness of the patient/bystander that the initial symptom was a stroke. Multivariable logistic regression analysis indicated that awareness of the patient/bystander that the initial symptom was a stroke (OR 4.438, 95% CI 2.669-7.381), knowledge about thrombolysis (OR 2.002, 95% CI 1.104-3.633) and use of ambulance (OR 1.961, 95% CI 1.176-3.270) were significantly associated with early arrival. CONCLUSIONS: In Korea, stroke awareness not only on the part of patients, but also of bystanders, had a great impact on early arrival at hospital. To increase the rate of thrombolysis therapy and the incidence of favorable outcomes, extensive general public education including how to recognize stroke symptoms would be important.ope

Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC

<p>Abstract</p> <p>Background</p> <p>RET/PTC (rearranged in transformation/papillary thyroid carcinomas) gene rearrangements are the most frequent genetic alterations identified in papillary thyroid carcinoma. Although it has been established that RET/PTC kinase plays a crucial role in intracellular signaling pathways that regulate cellular transformation, growth, and proliferation in thyroid epithelial cells, the upstream signaling that leads to the activation of RET/PTC is largely unknown. Based on the observation of high levels of PLD expression in human papillary thyroid cancer tissues, we investigated whether PLD plays a role in the regulating the RET/PTC-induced STAT3 activation.</p> <p>Methods</p> <p>Cancer tissue samples were obtained from papillary thyroid cancer patients (n = 6). The expression level of PLD was examined using immunohistochemistry and western blotting. Direct interaction between RET/PTC and PLD was analyzed by co-immunoprecipitation assay. PLD activity was assessed by measuring the formation of [³H]phosphatidylbutanol, the product of PLD-mediated transphosphatidylation, in the presence of <it>n</it>-butanol. The transcriptional activity of STAT3 was assessed by m67 luciferase reporter assay.</p> <p>Results</p> <p>In human papillary thyroid cancer, the expression levels of PLD2 protein were higher than those in the corresponding paired normal tissues. PLD and RET/PTC could be co-immunoprecipitated from cells where each protein was over-expressed. In addition, the activation of PLD by pervanadate triggered phosphorylation of tyrosine 705 residue on STAT-3, and its phosphorylation was dramatically higher in TPC-1 cells (from papillary carcinoma) that have an endogenous RET/PTC1 than in ARO cells (from anaplastic carcinoma) without alteration of total STAT-3 expression. Moreover, the RET/PTC-mediated transcriptional activation of STAT-3 was synergistically increased by over-expression of PLD, whereas the PLD activity as a lipid hydrolyzing enzyme was not affected by RET/PTC.</p> <p>Conclusion</p> <p>These findings led us to suggest that the PLD synergistically functions to activate the STAT3 signaling by interacting directly with the thyroid oncogenic kinase RET/PTC.</p