| 1. |
- Lange, Leslie A, et al.
(author)
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Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol.
- 2014
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 233-245
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Journal article (peer-reviewed)abstract
- Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.
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| 2. |
- Zhang, Yinping, et al.
(author)
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Ten cities cross-sectional questionnaire survey of children asthma and other allergies in China
- 2013
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In: Chinese Science Bulletin. - : Springer Science and Business Media LLC. - 1001-6538 .- 1861-9541. ; 58:34, s. 4182-4189
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Journal article (peer-reviewed)abstract
- Asthma, rhinitis and eczema (allergic or non-allergic) have increased throughout the world during the last decades, especially among children. Changes in the indoor environment are suspected to be important causes. China has experienced a dramatic change in indoor environmental exposures during the past two decades. However, such changes and their associations with children's asthma and other health aspects have not been thoroughly studied. China, Children, Homes, Health (CCHH), Phase I, was a cross-sectional questionnaire survey of 48219 children 1-8 years old in 10 Chinese cities during 2010-2012. The questionnaire includes the International Study of Asthma and Allergies in Childhood (ISAAC) core health questions and additional questions regarding housing, life habits and outdoor environment. In health analyses, children aged 3-6 years old were included. The prevalences of doctor diagnosed asthma varied from 1.7% to 9.8% (mean 6.8%), a large increase from 0.91% in 1999 and 1.50% in 2000. The prevalence of wheeze, rhinitis and atopic eczema (last 12 months) varied from 13.9% to 23.7%, 24.0% to 50.8% and 4.8% to 15.8%, respectively. Taiyuan had the lowest prevalences of all illnesses and Shanghai the highest, except for wheezewhere the highest value was for Urumqi. We found (1) no obvious association between disease prevalences and ambient PM10 concentrations and (2) higher prevalences of disease in humid climates with hot summers and cold winters, but with no centrally heated buildings. Associations between the diseases and economic status as indexed by Gross Domestic Product (GDP) requires further study.
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| 3. |
- Abdoullaye, Doukary, et al.
(author)
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Permanent genetic resources added to molecular ecology resources database 1 August 2009 - 30 September 2009
- 2010
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In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:1, s. 232-236
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Journal article (peer-reviewed)abstract
- This article documents the addition of 238 microsatellite marker loci and 72 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Adelges tsugae, Artemisia tridentata, Astroides calycularis, Azorella selago, Botryllus schlosseri, Botrylloides violaceus, Cardiocrinum cordatum var. glehnii, Campylopterus curvipennis, Colocasia esculenta, Cynomys ludovicianus, Cynomys leucurus, Cynomys gunnisoni, Epinephelus coioides, Eunicella singularis, Gammarus pulex, Homoeosoma nebulella, Hyla squirella, Lateolabrax japonicus, Mastomys erythroleucus, Pararge aegeria, Pardosa sierra, Phoenicopterus ruber ruber and Silene latifolia. These loci were cross-tested on the following species: Adelges abietis, Adelges cooleyi, Adelges piceae, Pineus pini, Pineus strobi, Tubastrea micrantha, three other Tubastrea species, Botrylloides fuscus, Botrylloides simodensis, Campylopterus hemileucurus, Campylopterus rufus, Campylopterus largipennis, Campylopterus villaviscensio, Phaethornis longuemareus, Florisuga mellivora, Lampornis amethystinus, Amazilia cyanocephala, Archilochus colubris, Epinephelus lanceolatus, Epinephelus fuscoguttatus, Symbiodinium temperate-A clade, Gammarus fossarum, Gammarus roeselii, Dikerogammarus villosus and Limnomysis benedeni. This article also documents the addition of 72 sequencing primer pairs and 52 allele specific primers for Neophocaena phocaenoides.
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| 4. |
- Li, Jian-Fang, et al.
(author)
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Soy isoflavone delays the progression of thioacetamide-induced liver fibrosis in rats
- 2011
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 46:3, s. 341-349
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Journal article (peer-reviewed)abstract
- Objective. Our aim was to investigate the effect of soy isoflavone (SI) on liver fibrosis in a thioacetamide (TAA)-induced rat model. Materials and methods. Twenty-eight rats were assigned to four groups: sham group, fibrosis group, low-dose treatment group (LDg) and high-dose treatment group (HDg). SI (90 or 270 mg/kg) was administered daily during the model development by TAA. Standard liver tests, platelet derived growth factor-BB (PDGF-BB) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured. The expression of collagen, alpha alpha-smooth muscle actin (alpha alpha-SMA) and transforming growth factor-beta beta 1 (TGF-beta beta 1) in liver tissue was determined. Electron microscopy was used to perform ultrastructural analysis of the livers. Results. Hepatic fibrosis was induced by 8 weeks of TAA administration. However, following the administration of SI, collagen staining significantly declined as compared with the fibrosis group (p < 0.01). Less collagen fibers around the hepatic stellate cells (HSCs) were observed in HDg as compared to the fibrosis group and LDg. There was no significant difference in standard liver tests between the fibrosis group and the two treatment groups. The levels of PDGF-BB and TIMP-1 in the two SI-treated groups were significantly lower than in the fibrosis group (p < 0.01). The expression of alpha alpha-SMA and TGF-beta beta 1 in HDg was less than that in the fibrosis group and LDg (p < 0.01). Conclusion. Administration of a high dose of SI resulted in an obvious inhibitory effect on liver fibrosis induced by TAA in rats. One hypothesis is that the effect may be related to the inhibition of HSC activation and proliferation.
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| 5. |
- Wang, Xiaofeng, et al.
(author)
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Evidence for type ia supernova diversity from ultraviolet observations with the hubble space telescope
- 2012
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 749:2, s. 126-
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Journal article (peer-reviewed)abstract
- We present ultraviolet (UV) spectroscopy and photometry of four Type Ia supernovae (SNe 2004dt, 2004ef, 2005M, and 2005cf) obtained with the UV prism of the Advanced Camera for Surveys on the Hubble Space Telescope. This data set provides unique spectral time series down to 2000 angstrom. Significant diversity is seen in the near-maximum-light spectra (similar to 2000-3500 angstrom) for this small sample. The corresponding photometric data, together with archival data from Swift Ultraviolet/Optical Telescope observations, provide further evidence of increased dispersion in the UV emission with respect to the optical. The peak luminositiesmeasured in the uvw1/F250W filter are found to correlate with the B-band light-curve shape parameter Delta m(15)(B), but with much larger scatter relative to the correlation in the broadband B band (e.g., similar to 0.4 mag versus similar to 0.2 mag for those with 0.8 mag < Delta m(15)(B) < 1.7 mag). SN 2004dt is found as an outlier of this correlation (at > 3 sigma), being brighter than normal SNe Ia such as SN 2005cf by similar to 0.9 mag and similar to 2.0 mag in the uvw1/F250W and uvm2/F220W filters, respectively. We show that different progenitor metallicity or line-expansion velocities alone cannot explain such a large discrepancy. Viewing-angle effects, such as due to an asymmetric explosion, may have a significant influence on the flux emitted in the UV region. Detailed modeling is needed to disentangle and quantify the above effects.
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| 6. |
- Werren, John H, et al.
(author)
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Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.
- 2010
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5963, s. 343-8
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Journal article (peer-reviewed)abstract
- We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
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| 7. |
- Zhang, Dan-Dan, et al.
(author)
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Functional evolution of a multigene family: Orthologous and paralogous pheromone receptor genes in the Turnip Moth, Agrotis segetum
- 2013
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10
-
Journal article (peer-reviewed)abstract
- Lepidopteran pheromone receptors (PRs), for which orthologies are evident among closely related species, provide an intriguing example of gene family evolution in terms of how new functions may arise. However, only a limited number of PRs have been functionally characterized so far and thus evolutionary scenarios suffer from elements of speculation. In this study we investigated the turnip moth Agrotis segetum, in which female moths produce a mixture of chemically related pheromone components that elicit specific responses from receptor cells on male antennae. We cloned nine A. segetum PR genes and the Orco gene by degenerate primer based RT-PCR. The nine PR genes, named as AsegOR1 and AsegOR3-10, fall into four distinct orthologous clusters of known lepidopteran PRs, of which one contains six paralogues. The paralogues are under relaxed selective pressure, contrasting with the purifying selection on other clusters. We identified the receptors AsegOR9, AsegOR4 and AsegOR5, specific for the respective homologous pheromone components (Z)-5-decenyl, (Z)-7-dodecenyl and (Z)-9-tetradecenyl acetates, by two-electrode voltage clamp recording from Xenopus laevis oocytes co-expressing Orco and each PR candidate. These receptors occur in three different orthologous clusters. We also found that the six paralogues with high sequence similarity vary dramatically in ligand selectivity and sensitivity. Different from AsegOR9, AsegOR6 showed a relatively large response to the behavioural antagonist (Z)-5-decenol, and a small response to (Z)-5-decenyl acetate. AsegOR1 was broadly tuned, but most responsive to (Z)-5-decenyl acetate, (Z)-7-dodecenyl acetate and the behavioural antagonist (Z)-8-dodecenyl acetate. AsegOR8 and AsegOR7, which differ from AsegOR6 and AsegOR1 by 7 and 10 aa respectively, showed much lower sensitivities. AsegOR10 showed only small responses to all the tested compounds. These results suggest that new receptors arise through gene duplication, and relaxed evolutionary constraints or positive selection among paralogues allow functional divergence to occur in spite of purifying selection being the norm.
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| 8. |
- Zhang, Xin, et al.
(author)
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A Longitudinal Study of Sick Building Syndrome (SBS) among Pupils in Relation to SO2, NO2, O-3 and PM10 in Schools in China
- 2014
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11, s. e112933-
-
Journal article (peer-reviewed)abstract
- There are fewer longitudinal studies from China on symptoms as described for the sick building syndrome (SBS). Here, we performed a two-year prospective study and investigated associations between environmental parameters such as room temperature, relative air humidity (RH), carbon dioxide (CO2), nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O-3), particulate matter (PM10), and health outcomes including prevalence, incidence and remission of SBS symptoms in junior high schools in Taiyuan, China. Totally 2134 pupils participated at baseline, and 1325 stayed in the same classrooms during the study period (2010-2012). The prevalence of mucosal symptoms, general symptoms and symptoms improved when away from school (school-related symptoms) was 22.7%, 20.4% and 39.2%, respectively, at baseline, and the prevalence increased during follow-up (P<0.001). At baseline, both indoor and outdoor SO2 were found positively associated with prevalence of school-related symptoms. Indoor O-3 was shown to be positively associated with prevalence of skin symptoms. At follow-up, indoor PM10 was found to be positively associated with new onset of skin, mucosal and general symptoms. CO2 and RH were positively associated with new onset of mucosal, general and school-related symptoms. Outdoor SO2 was positively associated with new onset of skin symptoms, while outdoor NO2 was positively associated with new onset of skin, general and mucosal symptoms. Outdoor PM10 was found to be positively associated with new onset of skin, general and mucosal symptoms as well as school-related symptoms. In conclusion, symptoms as described for SBS were commonly found in school children in Taiyuan City, China, and increased during the two-year follow-up period. Environmental pollution, including PM10, SO2 and NO2, could increase the prevalence and incidence of SBS and decrease the remission rate. Moreover, parental asthma and allergy (heredity) and pollen or pet allergy (atopy) can be risk factors for SBS.
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| 9. |
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| 10. |
- Albertsson, Anna-Maj, et al.
(author)
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The effect of osteopontin and osteopontin-derived peptides on preterm brain injury.
- 2014
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In: Journal of neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 11:1
-
Journal article (peer-reviewed)abstract
- BackgroundOsteopontin (OPN) is a highly phosphorylated sialoprotein and a soluble cytokine that is widely expressed in a variety of tissues, including the brain. OPN and OPN-derived peptides have been suggested to have potential neuroprotective effects against ischemic brain injury, but their role in preterm brain injury is unknown.MethodsWe used a hypoxia-ischemia (HI)-induced preterm brain injury model in postnatal day 5 mice. OPN and OPN-derived peptides were given intracerebroventricularly and intranasally before HI. Brain injury was evaluated at 7days after the insults.ResultsThere was a significant increase in endogenous OPN mRNA and OPN protein in the mouse brain after the induction of HI at postnatal day 5. Administration of full-length OPN protein and thrombin-cleaved OPN did not affect preterm brain injury. This was demonstrated with both intracerebroventricular and intranasal administration of OPN as well as in OPN-deficient mice. Interestingly, both N134¿153 and C154¿198 OPN-derived peptides increased the severity of brain injury in this HI-induced preterm brain injury model.ConclusionsThe neuroprotective effects of OPN are age-dependent, and, in contrast to the more mature brain, OPN-derived peptides potentiate injury in postnatal day 5 mice. Intranasal administration is an efficient way of delivering drugs to the central nervous system (CNS) in neonatal mice and is likely to be an easy and noninvasive method of drug delivery to the CNS in preterm infants.
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| 11. |
- Albertsson, Anna-Maj, et al.
(author)
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The immune response after hypoxia-ischemia in a mouse model of preterm brain injury.
- 2014
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In: Journal of neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 11:1
-
Journal article (peer-reviewed)abstract
- BackgroundPreterm brain injury consists primarily of periventricular leukomalacia accompanied by elements of gray-matter injury, and these injuries are associated with cerebral palsy and cognitive impairments. Inflammation is believed to be an important contributing factor to these injuries. The aim of this study was to examine the immune response in a postnatal day (PND) 5 mouse model of preterm brain injury induced by hypoxia-ischemia (HI) that is characterized by focal white and gray-matter injury.MethodsC57Bl/6 mice at PND 5 were subjected to unilateral HI induced by left carotid artery ligation and subsequent exposure to 10% O2 for 50 minutes, 70 minutes, or 80 minutes. At seven days post-HI, the white/gray-matter injury was examined. The immune responses in the brain after HI were examined at different time points after HI using RT-PCR and immunohistochemical staining.ResultsHI for 70 minutes in PND 5 mice induced local white-matter injury with focal cortical injury and hippocampal atrophy, features that are similar to those seen in preterm brain injury in human infants. HI for 50 minutes resulted in a small percentage of animals being injured, and HI for 80 minutes produced extensive infarction in multiple brain areas. Various immune responses, including changes in transcription factors and cytokines that are associated with a T-helper (Th)1/Th17-type response, an increased number of CD4+ T-cells, and elevated levels of triggering receptor expressed on myeloid cells 2 (TREM-2) and its adaptor protein DNAX activation protein of 12 kDa (DAP12) were observed using the HI 70 minute preterm brain injury model.ConclusionsWe have established a reproducible model of HI in PND 5 mice that produces consistent local white/gray-matter brain damage that is relevant to preterm brain injury in human infants. This model provides a useful tool for studying preterm brain injury. Both innate and adaptive immune responses are observed after HI, and these show a strong pro-inflammatory Th1/Th17-type bias. Such findings provide a critical foundation for future studies on the mechanism of preterm brain injury and suggest that blocking the Th1/Th17-type immune response might provide neuroprotection after preterm brain injury.
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| 12. |
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| 13. |
- Butler, Anne M., et al.
(author)
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Novel Loci Associated With PR Interval in a Genome-Wide Association Study of 10 African American Cohorts
- 2012
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In: Circulation: Cardiovascular Genetics. - 1942-325X. ; 5:6, s. 639-646
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Journal article (peer-reviewed)abstract
- Background-The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans. Methods and Results-We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and approximate to 2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (lambda range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (lambda: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0x10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0x10-8). Conclusions-This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent. (Circ Cardiovasc Genet. 2012;5:639-646.)
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| 14. |
- Cheng, Dan-Chen, et al.
(author)
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Improving Si solar cell performance using Mn:ZnSe quantum dot-doped PLMA thin film
- 2013
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In: Nanoscale Research Letters. - : SPRINGER. - 1931-7573 .- 1556-276X. ; 8
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Journal article (peer-reviewed)abstract
- Poly(lauryl methacrylate) (PLMA) thin film doped with Mn:ZnSe quantum dots (QDs) was spin-deposited on the front surface of Si solar cell for enhancing the solar cell efficiency via photoluminescence (PL) conversion. Significant solar cell efficiency enhancements (approximately 5% to 10%) under all-solar-spectrum (AM0) condition were observed after QD-doped PLMA coatings. Furthermore, the real contribution of the PL conversion was precisely assessed by investigating the photovoltaic responses of the QD-doped PLMA to monochromatic and AM0 light sources as functions of QD concentration, combined with reflectance and external quantum efficiency measurements. At a QD concentration of 1.6 mg/ml for example, among the efficiency enhancement of 5.96%, about 1.04% was due to the PL conversion, and the rest came from antireflection. Our work indicates that for the practical use of PL conversion in solar cell performance improvement, cautions are to be taken, as the achieved efficiency enhancement might not be wholly due to the PL conversion.
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| 15. |
- Crosby, Jacy, et al.
(author)
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Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease
- 2014
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 371:1, s. 22-31
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Journal article (peer-reviewed)abstract
- Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G -> A and IVS3+1G -> T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1x10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8x10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4x10(-6)). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)
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| 16. |
- Gu, Dong, et al.
(author)
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Growth of Single-Crystal Mesoporous Carbons with Im(3)over-barm Symmetry
- 2010
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In: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 22:16, s. 4828-4833
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Journal article (peer-reviewed)abstract
- Highly ordered mesoporous carbon FDU-16 rhombic dodecahedral single crystals with body-centered cubic structure (space group Im (3) over barm) have been successfully synthesized by employing an organic-organic assembly of triblock copolymer Pluronic F127 (EO106PO70EO106) and phenol/formaldehyde resol in basic aqueous solution. Synthetic factors (including reaction time, temperature, and stirring rate) are explored for controlling the formation of rhombic dodecahedral single crystals. The optimal stirring rate and the reaction temperature are 300 +/- 10 rpm and similar to 66 degrees C, respectively. High-resolution scanning electron microscopy (HRSEM), scanning transmission electron microscopy (STEM), and ultramicrotomy are applied to study the fine structures of the carbon single crystals. The mesopores are arranged in body-centered cubic symmetry throughout the entire particle. Surface steps are clearly observed in the {110} surface, which suggests a layer-by-layer growth of the mesoporous carbon FDU-16 single crystals. Cryo-SEM results from the reactant solution confirm the formation of resol/F127 unit micelles, further supporting the layer-by-layer growth process. The mesoporous carbon FDU-16 single crystals grow up to the final size of 2-4 mu m within 2 days. These findings may have consequences for the growth mechanism of other carbon materials in aqueous solution; moreover, the high-quality single crystals also have potential applications in nanodevice technologies.
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| 17. |
- Killela, Patrick J., et al.
(author)
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TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal
- 2013
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 110:15, s. 6021-6026
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Journal article (peer-reviewed)abstract
- Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low (<15%) and high (>= 15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.
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| 18. |
- Kilpeläinen, Tuomas O, et al.
(author)
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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
- 2011
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:8, s. 753-60
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Journal article (peer-reviewed)abstract
- Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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| 19. |
- Levovitz, Chaya, et al.
(author)
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TGFβ Receptor 1 : An Immune Susceptibility Gene in HPV-Associated Cancer
- 2014
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 74:23, s. 6833-6844
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Journal article (peer-reviewed)abstract
- Only a minority of those exposed to human papillomavirus (HPV) develop HPV-related cervical and oropharyngeal cancer. Because host immunity affects infection and progression to cancer, we tested the hypothesis that genetic variation in immune-related genes is a determinant of susceptibility to oropharyngeal cancer and other HPV-associated cancers by performing a multitier integrative computational analysis with oropharyngeal cancer data from a head and neck cancer genome-wide association study (GWAS). Independent analyses, including single-gene, gene-interconnectivity, protein-protein interaction, gene expression, and pathway analysis, identified immune genes and pathways significantly associated with oropharyngeal cancer. TGFβR1, which intersected all tiers of analysis and thus selected for validation, replicated significantly in the head and neck cancer GWAS limited to HPV-seropositive cases and an independent cervical cancer GWAS. The TGFβR1 containing p38-MAPK pathway was significantly associated with oropharyngeal cancer and cervical cancer, and TGFβR1 was overexpressed in oropharyngeal cancer, cervical cancer, and HPV(+) head and neck cancer tumors. These concordant analyses implicate TGFβR1 signaling as a process dysregulated across HPV-related cancers. This study demonstrates that genetic variation in immune-related genes is associated with susceptibility to oropharyngeal cancer and implicates TGFβR1/TGFβ signaling in the development of both oropharyngeal cancer and cervical cancer. Better understanding of the immunogenetic basis of susceptibility to HPV-associated cancers may provide insight into host/virus interactions and immune processes dysregulated in the minority of HPV-exposed individuals who progress to cancer. Cancer Res; 74(23); 6833-44.
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| 20. |
- Norbäck, Dan, et al.
(author)
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Respiratory symptoms, perceived air quality and physiological signs in elementary school pupils in relation to displacement and mixing ventilation system : an intervention study
- 2011
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In: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 21:5, s. 427-437
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Journal article (peer-reviewed)abstract
- Schools may be poorly ventilated and may contain furry pet allergens, particles and microorganisms. We studied health effects when changing from mixing ceiling ventilation to two types of displacement ventilation, front ventilation system (FVS) and floor master system (FMS). The study included pupils in three elementary school classes (N = 61), all with floor heating. One class received blinded interventions; the two others were unchanged (controls). Ventilation flow and supply air temperature was kept constant. The medical investigation included tear film stability (BUT), nasal patency and a questionnaire containing rating scales. When changing from mixing ventilation to FVS, the pupils (N = 26) perceived better air quality (P = 0.006) and less dyspnoea (P = 0.007) as compared to controls (N = 35), and BUT was improved (P = 0.03). At desk level, mean CO(2) was reduced from 867 to 655 ppm. Formaldehyde and viable bacteria were numerically lower, while total bacteria and molds were higher with displacement ventilation. There was no difference in symptoms or signs when changing from FVS to FMS. Cat (Der p1), dog (Can f1) and horse allergen (Equ cx) were common in air at all conditions. In conclusion, displacement ventilation may have certain positive health effects among pupils, as compared to conventional mixing ceiling systems.
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| 21. |
- Oepen, Stephan, et al.
(author)
-
SemEval 2014 Task 8: Broad-Coverage Semantic Dependency Parsing
- 2014
-
In: Proceedings of the 8th International Workshop on Semantic Evaluation (SemEval 2014). - : Association for Computational Linguistics. - 9781941643242 ; , s. 63-72
-
Conference paper (peer-reviewed)abstract
- Task 8 at SemEval 2014 defines Broad-Coverage Semantic Dependency Parsing (SDP) as the problem of recovering sentence-internal predicate–argument relationships for all content words, i.e. the semantic structure constituting the relational core of sentence meaning. In this task description, we position the problem in comparison to other sub-tasks in computational language analysis, introduce the semantic dependency target representations used, reflect on high-level commonalities and differences between these representations, and summarize the task setup, participating systems, and main results.
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| 22. |
- O'Seaghdha, Conall M., et al.
(author)
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Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations
- 2013
-
In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:9, s. e1003796-
-
Journal article (peer-reviewed)abstract
- Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in <= 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.
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| 23. |
- Parsa, Roham, et al.
(author)
-
Adoptive transfer of immunomodulatory M2 Macrophages prevents type 1 Diabetes in NOD Mice
- 2012
-
In: Diabetes. - : American diabetes Association. - 0012-1797 .- 1939-327X. ; 61:11, s. 2881-2892
-
Journal article (peer-reviewed)abstract
- Macrophages are multifunctional immune cells that may either drive or modulate disease pathogenesis depending on their activation phenotype. Autoimmune type 1 diabetes (T1D) is a chronic proinflammatory condition characterized by unresolved destruction of pancreatic islets. Adoptive cell transfer of macrophages with immunosuppressive properties represents a novel immunotherapy for treatment of such chronic autoimmune diseases. We used a panel of cytokines and other stimuli to discern the most effective regimen for in vitro induction of immunosuppressive macrophages (M2r) and determined interleukin (IL)-4/IL-10/transforming growth factor-beta (TGF-beta) to be optimal. M2r cells expressed programmed cell death 1 ligand-2, fragment crystallizable region gamma receptor IIlb, IL-10, and TGF-beta, had a potent deactivating effect on proinflammatory lipopolysaccharide/interferon-gamma-stimulated macrophages, and significantly suppressed T-cell proliferation. Clinical therapeutic efficacy was assessed after adoptive transfer in NOD T1D mice, and after a single transfer of M2r macrophages, >80% of treated NOD mice were protected against T1D for at least 3 months, even when transfer was conducted just prior to clinical onset. Fluorescent imaging analyses revealed that adoptively transferred M2r macrophages specifically homed to the inflamed pancreas, promoting 3-cell survival. We suggest that M2r macrophage therapy represents a novel intervention that stops ongoing autoimmune T1D and may have relevance in a clinical setting. Diabetes 61:2881-2892, 2012
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| 24. |
- Sharma, Manish, et al.
(author)
-
Older Patients with Myeloma Derive Similar Benefit from Autologous Transplantation
- 2014
-
In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:11, s. 1796-1803
-
Journal article (peer-reviewed)abstract
- Autologous hematopoietic cell transplantation (AHCT) for plasma cell myeloma is performed less often in people >70 years old than in people <= 70 years old. We analyzed 11,430 AHCT recipients for plasma cell myeloma prospectively reported to the Center for International Blood and Marrow Transplant Research between 2008 and 2011, representing the majority of US AHCT activity during this period. Survival (OS) was compared in 3 cohorts: ages 18 to 59 years (n = 5818), 60 to 69 years (n = 4666), and >70 years (n = 946). Median OS was not reached for any cohort. In multivariate analysis, increasing age was associated with mortality (P = .0006). Myeloma-specific mortality was similar among cohorts at 12%, indicating an age-related effect on nonmyeloma mortality. Analyses were performed in a representative subgroup comparing relapse rate, progression-free survival (PFS), and nonrelapse mortality (NRM). One-year NRM was 0% for age >70 years and 2% for other ages (P = not significant). The three-year relapse rate was 56% in age 18 to 59 years, 61% in age 60 to 69 years, and 63% age >70 (P = not significant). Three-year PFS was similar at 42% in age 18 to 59 years, 38% in age 60 to 69 years, and 33% in age >70 years (P = not significant). Postrelapse survival was significantly worse for the older cohort (P = .03). Older subjects selected for AHCT derived similar antimyeloma benefit without worse NRM, relapse rate, or PFS.
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| 25. |
- Smith, Gustav, et al.
(author)
-
The Impact of Ancestry and Common Genetic Variants on QT Interval in African Americans.
- 2012
-
In: Circulation: Cardiovascular Genetics. - 1942-325X. ; 5:6, s. 647-655
-
Journal article (peer-reviewed)abstract
- BACKGROUND: -Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death (SCD) and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. METHODS AND RESULTS: -First, individual estimates of African and European ancestry were inferred from genome-wide single nucleotide polymorphism (SNP) data in seven population-based cohorts of African Americans (n=12 097) and regressed on measured QT interval from electrocardiograms. Second, imputation was performed for 2.8 million SNPs and a genome-wide association (GWA) study of QT interval performed in ten cohorts (n=13 105). There was no evidence of association between genetic ancestry and QT interval (p=0.94). Genome-wide significant associations (p<2.5x10(-8)) were identified with SNPs at two loci, upstream of the genes NOS1AP (rs12143842, p=2x10(-15)) and ATP1B1 (rs1320976, p=2x10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low p-values (p<10(-5)) were observed for SNPs at several other loci previously identified in GWA studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF and PLN. CONCLUSIONS: -We observed no difference in duration of cardiac repolarization with global genetic indices of African ancestry. In addition, our GWA study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include African Americans.
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| 26. |
- Sun, Song, et al.
(author)
-
Evolution of Broad Spectrum beta-Lactam Resistance in an Engineered Metallo-beta-lactamase
- 2013
-
In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 288:4, s. 2314-2324
-
Journal article (peer-reviewed)abstract
- The extensive use and misuse of antibiotics during the last seven decades has led to the evolution and global spread of a variety of resistance mechanisms in bacteria. Of high medical importance are beta-lactamases, a group of enzymes inactivating beta-lactam antibiotics. Metallo-beta-lactamases (MBLs) are particularly problematic because of their ability to act on virtually all classes of beta-lactam antibiotics. An engineered MBL (evMBL9) characterized by low level activity with several beta-lactam antibiotics was constructed and employed as a parental MBL in an experiment to examine how an enzyme can evolve toward increased activity with a variety of beta-lactam antibiotics. We designed and synthesized a mutant library in which the substrate activity profile was varied by randomizing six active site amino acid residues. The library was expressed in Salmonella typhimurium, clones with increased resistance against seven different beta-lactam antibiotics (penicillin G, ampicillin, cephalothin, cefaclor, cefuroxime, cefoperazone, and cefotaxime) were isolated, and the MBL variants were characterized. For the majority of the mutants, bacterial resistance was significantly increased despite marked reductions in both mRNA and protein levels relative to those of parental evMBL9, indicating that the catalytic activities of these mutant MBLs were highly increased. Multivariate analysis showed that the majority of the mutant enzymes were generalists, conferring increased resistance against most of the examined beta-lactams.
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| 27. |
- Wang, Mojin, et al.
(author)
-
A-Kinase Anchoring Proteins 10 Expression in Relation to 2073A/G Polymorphism and Tumor Progression in Patients with Colorectal Cancer
- 2013
-
In: Pathology and Oncology Research. - : Springer Verlag (Germany). - 1219-4956 .- 1532-2807. ; 19:3, s. 521-527
-
Journal article (peer-reviewed)abstract
- The cAMP/PKA signalling events regulated by A-kinase anchoring proteins 10 (AKAP10) is involved in tumorigenesis. Previous study showed that AKAP10 polymorphism (2073 A/G, I646V) was associated with colorectal cancer risk. However, there was no literature reporting the role of AKAP10 in the pathogenesis of colorectal cancer. The aim of the study was to investigate the clinicopathologic significance of A-kinase anchoring proteins 10 (AKAP 10) expression and the relationship with its polymorphism in colorectal cancer. The expression of AKAP10 was determined by immunohistochemical staining (IHC) and western blot assay on colorectal cancer (n = 176), adenoma (n = 87) and distant normal mucosa (n = 72). 176 patients with colorectal cancer were genotyped for AKAP10 2073A/G polymorphism by TaqMan RT-PCR. We found that the positive expression rate of AKAP10 in colorectal cancer (59 %) was significantly higher than those in adenoma (39 %) and distant normal mucosa (42 %) (P = 0.004). There was no significant difference between adenoma and distant normal mucosa (P = 0.741). Positive AKAP10 staining was correlated with deeper tumor invasion (P < 0.001), lymph nodes metastasis (P = 0.022), advanced tumor stage (P < 0.001) and poorly differentiated degree (P = 0.003). Compared with AA genotype (52 %), positive expression of AKAP10 was significantly increased in colorectal cancer patients with the variant (AG+GG) genotypes (68 %, P = 0.033). It was concluded that AKAP10 may play an important role in the development and progression of colorectal cancer.
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| 28. |
- Xu, Ning, et al.
(author)
-
MicroRNA-125b down-regulates matrix metallopeptidase 13 and inhibits cutaneous squamous cell carcinoma cell proliferation, migration, and invasion.
- 2012
-
In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 287:35, s. 29899-908
-
Journal article (peer-reviewed)abstract
- Cutaneous squamous cell carcinoma (cSCC) is the second most common human cancer. Although dysregulation of microRNAs (miRNAs) is known to be involved in a variety of cancers, the role of miRNAs in cSCC is unclear. In this study, we aimed to identify tumor suppressive and oncogenic miRNAs involved in the pathogenesis of cSCC. MiRNA expression profiles in healthy skins (n = 4) and cSCCs (n = 4) were analyzed using MicroRNA Low Density Array. MiR-125b expression was analyzed by quantitative real-time PCR and in situ hybridization in skin biopsies from 40 healthy donors, 13 actinic keratosis, and 74 cSCC patients. The effect of miR-125b was analyzed in wound closure, colony formation, migration, and invasion assays in two cSCC cell lines, UT-SCC-7 and A431. The genes regulated by miR-125b in cSCC were identified by microarray analysis and its direct target was validated by luciferase reporter assay. Comparing cSCC with healthy skin, we identified four up-regulated miRNAs (miR-31, miR-135b, miR-21, and miR-223) and 54 down-regulated miRNAs, including miR-125b, whose function was further examined. We found that miR-125b suppressed proliferation, colony formation, migratory, and invasive capacity of cSCC cells. Matrix metallopeptidase 13 (MMP13) was identified as a direct target suppressed by miR-125b, and there was an inverse relationship between the expression of miR-125b and MMP13 in cSCC. Knockdown of MMP13 expression phenocopied the effects of miR-125b overexpression. These findings provide a novel molecular mechanism by which MMP13 is up-regulated in cSCCs and indicate that miR-125b plays a tumor suppressive role in cSCC.
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| 29. |
- Zhan, Qiuqiang, et al.
(author)
-
Using 915 nm Laser Excited Tm3+/Er3+/Ho3+-Doped NaYbF4 Upconversion Nanoparticles for in Vitro and Deeper in Vivo Bioimaging without Overheating Irradiation
- 2011
-
In: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 5:5, s. 3744-3757
-
Journal article (peer-reviewed)abstract
- Successful further development of superhigh-constrast upconversion (UC) bioimaging requires addressing the existing paradox: 980 nm laser light is used to excite upconversion nanoparticles (UCNPs), while 980 nm light has strong optical absorption of water and biological specimens. The overheating caused by 980 nm excitation laser light in UC bioimaging is computationally and experimentally investigated for the first time. A new promising excitation approach for better near-infrared to near-infrared (NIR-to-NIR) UC photoluminescence in vitro or in vivo imaging is proposed employing a cost-effective 915 nm laser. This novel laser excitation method provides drastically less heating of the biological specimen and larger imaging depth In the animals or tissues due to quite low water absorption. Experimentally obtained thermal-graphic maps of the mouse in response to the laser heating are investigated to demonstrate the less heating advantage of the 915 nm laser. Our tissue phantom experiments and simulations verified that the 915 nm laser is superior to the 980 nm laser for deep tissue imaging. A novel and facile strategy for surface functionalization is utilized to render UCNPs hydrophilic, stable, and cell targeting. These as-prepared UCNPs were characterized by TEM, emission spectroscopy, XRD, FTIR, and zeta potential. Specifically targeting UCNPs excited with a 915 nm laser have shown very high contrast UC bioimaging. Highly stable DSPE-mPEG-5000-encapsulated UCNPs were injected into mice to perform in vivo imaging. Imaging and spectroscopy analysis of UC photoluminescence demonstrated that a 915 nm laser can serve as a new promising excitation light for UC animal imaging.
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| 30. |
- Zhang, Cheng, 1987-, et al.
(author)
-
Contextual Modeling with Labeled Multi-LDA
- 2013
-
In: 2013 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS). - : IEEE. ; , s. 2264-2271
-
Conference paper (peer-reviewed)abstract
- Learning about activities and object affordances from human demonstration are important cognitive capabilities for robots functioning in human environments, for example, being able to classify objects and knowing how to grasp them for different tasks. To achieve such capabilities, we propose a Labeled Multi-modal Latent Dirichlet Allocation (LM-LDA), which is a generative classifier trained with two different data cues, for instance, one cue can be traditional visual observation and another cue can be contextual information. The novel aspects of the LM-LDA classifier, compared to other methods for encoding contextual information are that, I) even with only one of the cues present at execution time, the classification will be better than single cue classification since cue correlations are encoded in the model, II) one of the cues (e.g., common grasps for the observed object class) can be inferred from the other cue (e.g., the appearance of the observed object). This makes the method suitable for robot online and transfer learning; a capability highly desirable in cognitive robotic applications. Our experiments show a clear improvement for classification and a reasonable inference of the missing data.
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| 31. |
- Zhang, Dan, et al.
(author)
-
An integrated approach for remote manipulation of a high-performance reconfigurable parallel kinematic machine
- 2010
-
In: Journal of manufacturing systems. - : Elsevier. - 0278-6125 .- 1878-6642. ; 29:4, s. 164-172
-
Journal article (peer-reviewed)abstract
- Flexible and effective manipulation is important and meaningful for the further development and applications of parallel manipulators in the industrial fields, especially for high performance manufacturing. Web-based manufacturing has emerged as an alternative manufacturing technology in a distributed environment. In this paper, an integrated approach is proposed for remote manipulation of the reconfigurable parallel kinematic machine (RPKM) based on sensor-driven Wise-ShopFloor framework. The concept of Wise-ShopFloor integrates the modules of detailed architecture design, module interactions, sensor data utilization and model predictive control. In order to demonstrate the efficiency of this novel methodology, an example of a five degrees-of-freedom (DOF) RPKM is developed for surface finishing. The reconfigurability, the necessary kinematic analysis, and the performance mapping of the 5-DOF RPKM are conducted so as to implement the proposed approach.
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| 32. |
- Zhang, Dan, et al.
(author)
-
On performance enhancement of parallel kinematic machine
- 2013
-
In: Journal of Intelligent Manufacturing. - : Springer. - 0956-5515 .- 1572-8145. ; 24:2, s. 267-276
-
Journal article (peer-reviewed)abstract
- This paper proposes a spatial three degrees of freedom (DOF) parallel kinematic machine enhanced by a passive leg and a web-based remote control system. First, the geometric model of the parallel kinematic machine is addressed. In the mechanism, a fourth kinematic link-a passive link connecting the base center to the moving platform center-is introduced. Each of the three parallel limbs is actuated by one prismatic joint, respectively. The additional link has three passive DOF, namely two rotations around x and y axes and one translation along z axis. With the existence of this link, the unwanted motion of the tool (located in the moving platform) is constrained. The fourth link also enhances the global stiffness of the structure and distributes the torque from machining. With the kinematic model, a web-based remote control approach is applied. The concept of the web-based remote manipulation approach is introduced and the principles behind the method are explored in detail. Finally, a remote manipulation is demonstrated to the proposed structure using web-based remote control concept.
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| 33. |
- Zhang, Dan, et al.
(author)
-
Polymorphisms of Glucose-Regulated Protein 78 and Risk of Colorectal Cancer : A Case-Control Study in Southwest China
- 2013
-
In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:6
-
Journal article (peer-reviewed)abstract
- Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum chaperone, up-regulation serves as an efficient mechanism to promote malignant transformation of colorectal cancer (CRC) and protect CRC cells against apoptosis. Recently, the analysis of GRP78 polymorphisms has already determined that GRP78 rs391957 polymorphism could predict clinical outcome in CRC patients. Thus, we tested whether GRP78 polymorphisms are related to the risk of CRC. In this study, we detected two GRP78 polymorphisms (rs391957 (C>T) and rs430397 (G>A)) in 414 CRC cases and 502 hospital-based cancer-free healthy controls in Southwest China using a polymerase chain reaction–restriction fragment length polymorphism technique. Compared with the CC genotype, carriers of CT and TT genotypes of rs391957 polymorphism had higher risks of CRC (odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.06–1.83 for CT genotype and OR = 2.10, 95% CI = 1.06–4.14 for TT genotype, respectively). In CRC cases, the variant T allele was significantly associated with tumor invasion stage (P = 0.030), but not with status of lymph nodes metastasis (P = 0.052). Compared with the GG genotype, carriers of GA and AA genotypes of rs430397 polymorphism had higher risks of CRC (OR = 1.63, 95% CI = 1.23–2.15 for GA genotype and OR = 2.92, 95% CI = 1.23–6.94 for AA genotype, respectively). The rs430397 polymorphism was not associated with the clinicopathological characteristics of CRC. These data provide the first evidence that GRP78 rs391957 and rs430397 polymorphisms could serve as markers to predict the risk of CRC.
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| 34. |
- Zhang, Fan, et al.
(author)
-
In situ investigations of Fe3+ induced complexation of adsorbed Mefp-1 protein film on iron substrate
- 2013
-
In: Journal of Colloid and Interface Science. - : Academic Press. - 0021-9797 .- 1095-7103. ; 404, s. 62-71
-
Journal article (peer-reviewed)abstract
- A range of in situ analytical techniques and theoretical calculations were applied to gain insights into the formation and properties of the Mefp-I film on iron substrate, as well as the protein complexation with Fe3+ ions. Adsorption kinetics of Mefp-1 and the complexation were investigated using QCM-D. The results suggest an initially fast adsorption, with the molecules oriented preferentially parallel to the surface, followed by a structural change within the film leading to molecules extending toward solution. Exposure to a diluted FeCl3 solution results in enhanced complexation within the adsorbed protein film, leading to water removal and film compaction. In situ Peak Force Tapping AFM was employed for determining morphology and nano-mechanical properties of the surface layer. The results, in agreement with the QCM-D observations, demonstrate that addition of Fe-3 induces a transition from an extended and soft protein layer to a denser and stiffer one. Further, in situ ATR-FTIR and Confocal Raman Micro-spectroscopy (CRM) techniques were utilized to monitor compositional/structural changes in the surface layer due to addition of Fe3+ ions. The spectroscopic analyses assisted by DFT calculations provide evidence for formation of tri-Fe3+/catechol complexes in the surface film, which is enhanced by Fe3+ addition.
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| 35. |
- Zhang, J., et al.
(author)
-
Broadband Gm-Boosted Differential HBT Doublers With Transformer Balun
- 2011
-
In: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480 .- 1557-9670. ; 59:11, s. 2953-2960
-
Journal article (other academic/artistic)abstract
- Broadband monolithic InGaP HBT frequency doublers for K-band application have been developed. The designs employ a Gm-boosted differential common-base configuration using either capacitive or transformer-based coupling between base and emitters. To the authors' best knowledge, these are the first frequency doublers utilizing the Gm-boosted configuration and the result demonstrate larger bandwidth and higher output power than any previously reported frequency doublers. The design with cross-coupled capacitors presents a fundamental rejection better than 20 dB over a 100% 3-dB bandwidth, extending from 6 to 18 GHz. The transformer-coupled design has about 15-dB fundamental rejection over a slightly narrower bandwidth extending from 7 to 16 GHz. Both doublers have conversion gain peaking at more than -0.8 dB and output power Psat > 13 dBm. The designs are also very compact with chip sizes less than 0.5 mm(2).
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| 36. |
- Zhang, Jian, 1978, et al.
(author)
-
Transformer-Based Broadband High-Linearity HBT Gm-Boosted Transconductance Mixers
- 2014
-
In: IEEE Transactions on Microwave Theory and Techniques. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9480 .- 1557-9670. ; 62:1, s. 92-99
-
Journal article (peer-reviewed)abstract
- A Gm-boosted transconductance configuration mixer is proposed. Based on this topology, two broadband monolithic InGaP HBT mixers, one single device and one balanced, have been developed for C-Ku-band applications. The single device mixer has a conversion gain of 4.5 +/- 1.5 dB within the RF frequency range from 5 to 17 GHz. The balanced design has about 3.5 +/- 1.5-dB conversion gain within a frequency range of 6-18 GHz. The two mixers have very good linearity with a third-order intermodulation intercept point (IIP3) higher than 16 and 20 dBm for the single device mixer and single balanced mixer, respectively. Both mixers are pumped by a local oscillator power of 5 dBm. To the authors' best knowledge, the designed mixers demonstrate the highest IIP3 with positive conversion gain in this frequency range. Compact designs are achieved with chip sizes less than 0.5 mm(2). DC power consumptions are 30 and 50 mW, for the single device and single balanced mixer, respectively.
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| 37. |
- Zhang, Penghua, et al.
(author)
-
Engineering BspQI nicking enzymes and application of N.BspQI in DNA labeling and production of single-strand DNA
- 2010
-
In: Protein Expression and Purification. - : Elsevier BV. - 1046-5928. ; 69:2, s. 226-234
-
Journal article (peer-reviewed)abstract
- BspQI is a thermostable Type IIS restriction endonuclease (REase) with the recognition sequence 5′GCTCTTC N1/N4 3′. Here we report the cloning and expression of the bspQIR gene for the BspQI restriction enzyme in Escherichia coli. Alanine scanning of the BspQI charged residues identified a number of DNA nicking variants. After sampling combinations of different amino acid substitutions, an Nt.BspQI triple mutant (E172A/E248A/E255K) was constructed with predominantly top-strand DNA nicking activity. Furthermore, a triple mutant of BspQI (Nb.BspQI, N235A/K331A/R428A) was engineered to create a bottom-strand nicking enzyme. In addition, we demonstrated the application of Nt.BspQI in optical mapping of single DNA molecules. Nt or Nb.BspQI-nicked dsDNA can be further digested by E. coli exonuclease III to create ssDNA for downstream applications. BspQI contains two potential catalytic sites: a top-strand catalytic site (Ct) with a D-H-N-K motif found in the HNH endonuclease family and a bottom-strand catalytic site (Cb) with three scattered Glu residues. BlastP analysis of proteins in GenBank indicated a putative restriction enzyme with significant amino acid sequence identity to BspQI from the sequenced bacterial genome Croceibacter atlanticus HTCC2559. This restriction gene was amplified by PCR and cloned into a T7 expression vector. Restriction mapping and run-off DNA sequencing of digested products from the partially purified enzyme indicated that it is an EarI isoschizomer with 6-bp recognition, which we named CatHI (CTCTTC N1/N4).
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| 38. |
- Zhang, Xin, et al.
(author)
-
A longitudinal study of sick building syndrome among pupils in relation to microbial components in dust in schools in China
- 2011
-
In: Science of the Total Environment. - : Elsevier BV. - 1879-1026 .- 0048-9697. ; 409:24, s. 5253-5259
-
Journal article (peer-reviewed)abstract
- There are few longitudinal studies on sick building syndrome (SBS), which include ocular, nasal, throat, and dermal symptoms, headache, and fatigue. We studied the associations between selected microbial components, fungal DNA, furry pet allergens, and incidence and remission of SBS symptoms in schools in Taiyuan, China. The study was based on a two-year prospective analysis in pupils (N = 1143) in a random sample of schools in China. Settled dust in the classrooms was collected by vacuum cleaning and analyzed for lipopolysaccharide (LPS), muramic acid (MuA), and ergosterol (Erg). Airborne dust was collected in Petri dishes and analyzed for cat and dog allergens and fungal DNA. The relationship between the concentration of allergens and microbial compounds and new onset of SBS was analyzed by multi-level logistic regression. The prevalence of mucosal and general symptoms was 33% and 28%, respectively, at baseline, and increased during follow-up. At baseline, 27% reported at least one symptom that improved when away from school (school-related symptoms). New onset of mucosal symptoms was negatively associated with concentration of MuA, total LPS, and shorter lengths of 3-hydroxy fatty acids from LPS, 04, 06, and C18. Onset of general symptoms was negatively associated with C18 LPS. Onset of school-related symptoms was negatively associated with C16 LPS, but positively associated with total fungal DNA. In general, bacterial compounds (LPS and MuA) seem to protect against the development of mucosal and general symptoms, but fungal exposure measured as fungal DNA could increase the incidence of school-related symptoms. (C) 2011 Elsevier B.V. All rights reserved.
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| 39. |
- Zhang, Xin, et al.
(author)
-
Dampness and moulds in workplace buildings : Associations with incidence and remission of sick building syndrome (SBS) and biomarkers of inflammation in a 10 year follow-up study
- 2012
-
In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 430, s. 75-81
-
Journal article (peer-reviewed)abstract
- There are few longitudinal studies on health effects of dampness and moulds in workplace buildings. We studied associations between dampness and indoor moulds in workplace buildings and selected biomarkers as well as incidence and remission of sick building syndrome (SBS). The study was based on a ten-year prospective study (1992-2002) in a random sample of adults (N=429) from the Uppsala part of the European Community Respiratory Health Survey (ECRHS). The 10-year incidence (onset) of general, mucosal, dermal symptoms and any symptom improved when away from the workplace (work-related symptoms) was 7.2%, 11.6%, 6.4% and 9.4% respectively. The 10-year remission of general, mucosal, dermal symptoms and work-related symptoms was 71.4%, 57.1%, 70.4% and 72.2% respectively. Signs of dampness in the floor construction in any workplace building during follow up (cumulative exposure) was associated with incidence of mucosal symptoms (OR=2.43). Cumulative exposure to moldy odor was associated with incidence of work-related symptoms (OR=2.69). Cumulative exposure to dampness or moulds was associated with decreased remission of work-related symptoms (OR=0.20 for water leakage, OR=0.17 for floor dampness, and OR=0.17 for visible indoor mould growth). Working in a building repaired because of dampness (repaired building) or mould was associated with decreased remission of work-related symptoms (OR=0.32). Any dampness or moulds at baseline in the workplace building was associated with increased bronchial responsiveness (BR) and higher levels of Eosinphilic Cationic Protein (ECP) in serum and Eosinophilic counts in blood at baseline. Cumulative exposure to dampness and moulds, and work in a repaired building, was associated with increased BR at follow-up. In general, dampness and moulds in the workplace building is associated with increased incidence and decreased remission of SBS, as well as increased bronchial responsiveness and eosinophilic inflammation.
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| 40. |
- Zhang, X, et al.
(author)
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The prevalence and incidence of sick building syndrome in Chinese pupils in relation to the school environment : a two-year follow-up study
- 2011
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In: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 21:6, s. 462-471
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Journal article (peer-reviewed)abstract
- There are few incidence studies on sick building syndrome (SBS). We studied two-year change of SBS in Chinese pupils in relation to parental asthma/allergy (heredity), own atopy, classroom temperature, relative humidity (RH), absolute humidity (AH), crowdedness, CO₂, NO₂, and SO₂. A total of 1993 participated at baseline, and 1143 stayed in the same classrooms after two years. The prevalence of mucosal and general symptoms was 33% and 28% at baseline and increased during follow-up (P < 0.001). Twenty-seven percent reported at least one symptom improved when away from school. Heredity and own atopy were predictors of SBS at baseline and incidence of SBS. At baseline, SO₂ was associated with general symptoms (OR=1.10 per 100 μg/m³), mucosal symptoms (OR=1.12 per 100 μg/m³), and skin symptoms (OR=1.16 per 100 μg/m³). NO₂ was associated with mucosal symptoms (OR=1.13 per 10 μg/m³), and symptoms improved when away from school (OR=1.13 per 10 μg/m³). Temperature, RH, AH, and CO₂ were negatively associated with prevalence of SBS. Incidence or remission of SBS was not related to any exposure, except a negative association between SO₂ and new skin symptoms. In conclusion, heredity and atopy are related to incidence and prevalence of SBS, but the role of the measured exposures for SBS is more unclear. PRACTICAL IMPLICATIONS: We found high levels of CO₂ indicating inadequate ventilation and high levels of SO₂ and NO₂, both indoors and outdoors. All schools had natural ventilation, only. Relying on window opening as a tool for ventilation in China is difficult because increased ventilation will decrease the level of CO₂ but increase the level of NO₂ and SO₂ indoors. Prevalence studies of sick building syndrome (SBS) might not be conclusive for causal relationships, and more longitudinal studies on SBS are needed both in China and other parts of the world. The concept of mechanical ventilation and air filtration should be introduced in the schools, and when planning new schools, locations close to heavily trafficked roads should be avoided.
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| 41. |
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| 42. |
- Zhao, Zhuohui, et al.
(author)
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Fractional exhaled nitric oxide in Chinese children with asthma and allergies : A two-city study
- 2013
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In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 107:2, s. 161-171
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Journal article (peer-reviewed)abstract
- Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker of eosinophilic airway inflammation. Our aim was to study associations between FeNO in Chinese children in two cities and asthma, asthmatic symptoms, rhinitis, eczema, and selected childhood and home environmental factors. A random sample of children in Shanghai (n = 187) and Taiyuan (n = 127), and additional randomly selected children reporting current wheeze (n = 115) were invited for FeNO measurements by NIOX MINO. A questionnaire survey was performed among all subjects (12-14 y) in 59 classes in Shanghai and 44 in Taiyuan. Associations were studied using multiple linear regression using 10log transformed FeNO data and mutual adjustment. The geometric mean FeNO in the random sample (GM ± GSD) was higher in Shanghai (16.2 ± 1.9 ppb) as compared to Taiyuan (12.8 ± 1.6 ppb) (P < 0.001). In the total material (n = 429), Shanghai residency (P = 0.001), male gender (P = 0.02), parental asthma/allergy (P = 0.04), doctors' diagnosed asthma (DDA) (P < 0.001) and current wheeze (P < 0.001) were associated with higher FeNO levels. In non-wheezers (n = 291), Shanghai residency (P = 0.007), male gender (P = 0.002), DDA (P = 0.04), current rhinitis (P = 0.004) and reported pollen/furry pet allergy (P = 0.04) were positively associated with FeNO. In wheezers (n = 138), DDA was the only significant factor (P = 0.009). In conclusion, male gender, current wheeze, DDA, parental asthma/allergy, current rhinitis, pollen/furry pet allergy can be independent determinants of increased FeNO. The lower level of FeNO in Taiyuan is in agreement with previous studies showing lower prevalence of asthma and allergy in Taiyuan as compared to Shanghai.
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| 43. |
- ZhuoHui, Zhao, et al.
(author)
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Prenatal and early life home environment exposure in relation to preschool children's asthma, allergic rhinitis and eczema in Taiyuan, China
- 2013
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In: Chinese Science Bulletin. - : Springer Science and Business Media LLC. - 1001-6538 .- 1861-9541. ; 58:34, s. 4245-4251
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Journal article (peer-reviewed)abstract
- Prenatal and early life home environment might be related to children's asthma or allergic diseases later in life. A cross-sectional epidemiological study was designed and a questionnaire survey was performed in 3700 preschool children in urban areas in Taiyuan, Shanxi Province, China. Questions on children's asthma and allergic diseases from the International Study on Asthma and Allergies in Childhood (ISAAC) were integrated with questions on home environment from the Swedish Dampness in Buildings and Health (DBH) study, appropriately modified for Chinese life habits. By multivariate regression analyses controlling for age, gender, heredity, location in urban/suburban or rural areas, environmental tobacco smoke (ETS) and breastfeeding, we found that home new furniture (HNF) before birth (referring to 1 year before pregnancy and during pregnancy) was positively associated with wheezing ever (odds ratio(OR) 1.23 with 95% CI of 1.03-1.48) and wheezing last 12 months (1.24,1.00-1.54), allergic rhinitis (AR) (1.26,1.06-1.51), and eczema (1.42,1.01-1.99). HNF between 0-1 years old was also positively associated with wheezing last 12 months. Home new decoration (HND) during 0-1 years old was positively associated with AR symptoms and eczema symptoms, more in the last 12 months. Stronger positive associations were found for signs of home mold and dampness with almost all children's asthmatic and allergic symptoms (OR ranging from 1.23-1.85, P<0.05). By mutual adjustment between HNF before children's birth and home mold or dampness, all the significance remained unchanged. Prenatal HNF and home mold or dampness was independently associated with children's asthmatic and allergic diseases later in life.
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