| 1. |
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| 2. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 3. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 4. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 5. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 6. |
- Wang, Peng-Fei, et al.
(författare)
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A novel self-refreshable capacitorless DRAM cell and its extended applications
- 2010
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Ingår i: Solid-State Electronics. - : Elsevier BV. - 0038-1101 .- 1879-2405. ; 54:9, s. 985-990
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Tidskriftsartikel (refereegranskat)abstract
- A novel DRAM cell based on floating junction gate (FJG) concept is investigated for its extended applications. Compared to the two-transistor floating gate DRAM cell, the new memory cell investigated in the present work has a much simpler configuration with only one transistor. Besides, its write speed is improved by introducing an integrated gated-diode so that state “1” can be self-refreshable. In this paper, the device configuration, the DRAM application feasibility, the self-refreshing ability, and the non-destructive read are explored. In addition, extended applications of the DRAM cell using the FJG concept will be discussed.
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| 7. |
- Alonso-Blanco, Carlos, et al.
(författare)
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1,135 Genomes Reveal the Global Pattern of Polymorphism in Arabidopsis thaliana
- 2016
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Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 481-491
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Tidskriftsartikel (refereegranskat)abstract
- Arabidopsis thaliana serves as a model organism for the study of fundamental physiological, cellular, and molecular processes. It has also greatly advanced our understanding of intraspecific genome variation. We present a detailed map of variation in 1,135 high-quality re-sequenced natural inbred lines representing the native Eurasian and North African range and recently colonized North America. We identify relict populations that continue to inhabit ancestral habitats, primarily in the Iberian Peninsula. They have mixed with a lineage that has spread to northern latitudes from an unknown glacial refugium and is now found in a much broader spectrum of habitats. Insights into the history of the species and the fine-scale distribution of genetic diversity provide the basis for full exploitation of A. thaliana natural variation through integration of genomes and epigenomes with molecular and non-molecular phenotypes.
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| 8. |
- Fan, Jin, et al.
(författare)
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Development of wideband orthomode transducers for FAST cryogenic receiver system
- 2020
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Ingår i: Research in Astronomy and Astrophysics. - : IOP Publishing. - 1674-4527. ; 20:5
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the design, construction, and performance of the wideband orthomode transducers (OMTs) for the L- (1.2-1.8 GHz), the S- (2-3 GHz) and the P- (0.56-1.12 GHz) band receiver systems of the Five-hundred-meter Aperture Spherical radio Telescope (FAST). These OMTs operate at the cryogenic temperature of 70K to reduce their thermal noise contribution to the receiver chains. The development on the FAST L- and S-band quad-ridged waveguide (QRWG) OMTs is carried out based on the theoretical mode analysis. In view of the miniaturization of FAST cryogenic receiver system at P-band, a novel wideband compact bowtie dipole OMT is designed with an octave bandwidth as well as a length of only quarter wavelength. The proposed L-, S- and P-band OMTs are designed and optimized by using Ansys High Frequency Structure Simulator (HFSS), and then manufactured, tested at room temperature. Measurement of FAST cryogenic receiver system noise is also performed with the L-, S- and P-band OMTs installed. The measured results fully comply with the design specifications.
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| 9. |
- Gan, Wensheng, et al.
(författare)
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Utility-Driven Data Analytics on Uncertain Data
- 2020
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Ingår i: IEEE Systems Journal. - : IEEE. - 1932-8184 .- 1937-9234. ; 14:3, s. 4442-4453
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Tidskriftsartikel (refereegranskat)abstract
- Modern Internet of Things (IoT) applications generate massive amounts of data, much of them in the form of objects/items of readings, events, and log entries. Specifically, most of the objects in these IoT data contain rich embedded information (e.g., frequency and uncertainty) and different levels of importance (e.g., unit risk/utility of items, interestingness, cost, or weight). Many existing approaches in data mining and analytics have limitations, such as only the binary attribute is considered within a transaction, as well as all the objects/items having equal weights or importance. To solve these drawbacks, a novel utility-driven data analytics algorithm named HUPNU is presented in this article. As a general utility-driven uncertain data mining model, HUPNU can extract High-Utility patterns by considering both Positive and Negative unit utilities from Uncertain data. The qualified high-utility patterns can be effectively discovered for intrusion detection, risk prediction, manufacturing management, and decision-making, among others. By using the developed vertical Probability-Utility list with the positive and negative utilities structure, as well as several effective pruning strategies, experiments showed that the developed HUPNU approach with the pruning strategies performed great in mining the qualified patterns efficiently and effectively.
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| 10. |
- Gan, Yong, et al.
(författare)
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Association between alcohol consumption and the risk of stroke in middle-aged and older adults in China
- 2021
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Ingår i: Drug And Alcohol Dependence. - : Elsevier BV. - 0376-8716 .- 1879-0046. ; 229
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to investigate the association between alcohol consumption and the prevalence of stroke in Chinese adults aged 40 years and over.Method: We conducted a cross-sectional analysis among 113,573 Chinese adults aged >= 40 years in the China National Stroke Prevention Project (2014-2015) to examine correlations of alcohol consumption with the prevalence of stroke. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), controlling for various confounders, e.g., gender, age, smoking, physical activity and other health conditions.Results: Within the study population, a total of 12,753 stroke survivors were identified. The prevalence of light to moderate and of heavy alcohol consumption was 10.1% and 5.7% respectively. The multivariate logistic regression results show that light to moderate alcohol consumption was associated with reduced risk of stroke of all types [0.91 (95%CI: 0.85-0.97)] and of ischemic stroke [0.90 (0.84-0.97)]. No association was found between alcohol consumption and hemorrhagic stroke. Compared with abstainers, the adjusted ORs of all stroke were 0.83 (0.75-0.92) for those who drank 11-20 years, and no association was found between 1 and 10 years or over 20 years of drinking and risk of stroke.Conclusions: These results indicate that light to moderate alcohol consumption may be protective against all and ischemic stroke, and heavy drinking was not significantly associated with risk of all stroke in China. No association between alcohol consumption and hemorrhagic stroke was found.
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| 11. |
- Geng, Xiaofei, et al.
(författare)
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Year-Round Measurements of Dissolved Black Carbon in Coastal Southeast Asia Aerosols : Rethinking Its Atmospheric Deposition in the Ocean
- 2021
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Ingår i: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 126:18
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Tidskriftsartikel (refereegranskat)abstract
- Dissolved black carbon (DBC) is an important recalcitrant fraction of marine dissolved organic matter. Riverine discharge is the largest known source of oceanic DBC; however, the significance of atmospheric deposition as a source of oceanic DBC remains poorly understood. In this study, year-round aerosol sampling was carried out at a rural coastal site in Southeast Asia for DBC analysis using the benzene polycarboxylic acid (BPCA) method. The results revealed the uncertainty of an earlier estimate of the atmospheric deposition flux of DBC to the global ocean (FDBC), which assumed a linear correlation between DBC and water-soluble organic carbon (WSOC). The correlation between DBC and WSOC depended on the sources of carbonaceous aerosols. The DBC/WSOC ratios were higher for the biomass burning aerosols. DBC was linearly correlated with black carbon (BC) for biomass or fossil fuel combustion aerosols. However, the DBC/BC ratios were higher for biomass burning aerosols (0.41 ± 0.22), whereas lower for fossil fuel combustion aerosols (0.04 ± 0.03). FDBC was revisited based on the relationship between DBC and BC. FDBC is primarily contributed by biomass burning aerosols and maybe previously underestimated. In this study, the DBC in aerosols had less condensed aromatic structures than the DBC present in the major rivers of the world, as shown by the BPCA compositions. This indicated that oceanic DBC sourced from atmospheric deposition was less likely to be removed by photodegradation and sedimentation, as compared to the DBC sourced from riverine discharge.
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| 12. |
- He, Wei, et al.
(författare)
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Recent development and application of thermoelectric generator and cooler
- 2015
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Ingår i: Applied Energy. - : Elsevier BV. - 0306-2619 .- 1872-9118. ; 143, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- Energy crisis and environment deterioration are two major problems for 21st century. Thermoelectric device is a promising solution for those two problems. This review begins with the basic concepts of the thermoelectric and discusses its recent material researches about the figure of merit. It also reports the recent applications of the thermoelectric generator, including the structure optimization which significantly affects the thermoelectric generator, the low temperature recovery, the heat resource and its application area. Then it reports the recent application of the thermoelectric cooler including the thermoelectric model and its application area. It ends with the discussion of the further research direction.
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| 13. |
- Huang, Daming, et al.
(författare)
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A Modified Charge-Pumping Method for the Characterization of Interface-Trap Generation in MOSFETs
- 2009
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Ingår i: IEEE Transactions on Electron Devices. - 0018-9383 .- 1557-9646. ; 56:2, s. 267-274
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Tidskriftsartikel (refereegranskat)abstract
- A novel recovery-free interface-trap measurement method is presented in detail. This method is the modification of the conventional charge pumping (CP) by extending the pulse low level to the stress-bias and minimizing the pulse high-level duty cycle to suppress the recovery effect. The method is applied to study the negative-bias temperature instability in p-MOSFETs. As compared with the conventional CP, a much larger interface-trap generation under stress is observed by the new method. A power law time dependence (similar to t(n)) of interface-trap generation is observed. The index n. is less than that derived from conventional CP and increases with temperature, demonstrating a dispersive process involved in the trap generation dynamics.
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| 14. |
- Hui, Zhixuan, et al.
(författare)
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TGFβ-induced EN1 promotes tumor budding of adenoid cystic carcinoma in patient-derived organoid model
- 2024
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 154:10, s. 1814-1827
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Tidskriftsartikel (refereegranskat)abstract
- Adenoid cystic carcinoma (ACC) and basal cell adenoma (BCA) share many histological characteristics and often need a differential diagnosis in clinical pathology. Recently, we found homeobox protein engrailed-1 (EN1) was a potential diagnostic marker for ACC in an organoids library of salivary gland tumors (SGTs). Here we aim to confirm EN1 as a differential diagnostic marker for ACC, and further investigate the regulatory mechanism and biological function of EN1 in tumor progression. The transcriptional analysis, quantitative polymerase chain reaction, Western blot and immunohistochemistry staining were performed and revealed that EN1 was specifically and highly expressed in ACC, and accurately differentiated ACC from BCA. Furthermore, TGFβ signaling pathway was found associated with ACC, and the regulation of EN1 through TGFβ was detected in the human ACC cell lines and patient-derived organoids (PDOs). TGFβ-induced EN1 was important in promoting tumor budding in the PDOs model. Interestingly, a high level of EN1 and TGFβ1 in the budding tips was observed in ACC clinical samples, and the expression of EN1 and TGFβ1 in ACC was significantly associated with the clinical stage. In summary, our study verified EN1 is a good diagnostic marker to differentiate ACC from BCA. TGFβ-induced EN1 facilitates the tumor budding of ACC, which might be an important mechanism related to the malignant phenotype of ACC.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Kawakatsu, Taiji, et al.
(författare)
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Epigenomic Diversity in a Global Collection of Arabidopsis thaliana Accessions
- 2016
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Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 166:2, s. 492-505
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Tidskriftsartikel (refereegranskat)abstract
- The epigenome orchestrates genome accessibility, functionality, and three-dimensional structure. Because epigenetic variation can impact transcription and thus phenotypes, it may contribute to adaptation. Here, we report 1,107 high-quality single-base resolution methylomes and 1,203 transcriptomes from the 1001 Genomes collection of Arabidopsis thaliana. Although the genetic basis of methylation variation is highly complex, geographic origin is a major predictor of genome-wide DNA methylation levels and of altered gene expression caused by epialleles. Comparison to cistrome and epicistrome datasets identifies associations between transcription factor binding sites, methylation, nucleotide variation, and co-expression modules. Physical maps for nine of the most diverse genomes reveal how transposons and other structural variants shape the epigenome, with dramatic effects on immunity genes. The 1001 Epigenomes Project provides a comprehensive resource for understanding how variation in DNA methylation contributes to molecular and non-molecular phenotypes in natural populations of the most studied model plant.
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| 20. |
- Liang, Kai, et al.
(författare)
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A Fair Power Splitting Algorithm for Simultaneous Wireless Information and Energy Transfer in CoMP Downlink Transmission
- 2015
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Ingår i: Wireless personal communications. - : SPRINGER. - 0929-6212 .- 1572-834X. ; 85:4, s. 2687-2710
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Tidskriftsartikel (refereegranskat)abstract
- A power splitting approach for simultaneous wireless information and energy transfer is provided in this paper. We consider coordinated multipiont downlink transmission with M base stations (BSs) and J mobile stations (MSs). The main goal of this paper is to maximize per-MS data rate and receiving energy by dynamically optimizing transmitting beamformer. To improve fairness, this problem can be formulated to maximize the minimum rate of all J MSs with per-BS transmitting power constraints and per-MS receiving energy constraints, which is NP-hard problem. Minimum mean square error receiver, affine approximation and alternative convex optimization (ACO) methods are introduced to decompose the original NP-hard problem to several convex subproblems which can be solved by second-order cone programming with low rank (which is equal to the number of data streams) solutions, and then a fast heuristic algorithm is provided to solve the original problem. Numerical results show that the proposed algorithm can achieve fairness, and outperforms sum rate scheme in terms of fairness and outage probability. The fast convergency also demonstrates the proposed algorithms good performance.
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| 21. |
- Liu, Junwen, et al.
(författare)
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Isotope constraints of the strong influence of biomass burning to climate-forcing Black Carbon aerosols over Southeast Asia
- 2020
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 744
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Tidskriftsartikel (refereegranskat)abstract
- Black Carbon (BC) deteriorates air quality and contributes to climate warming, yet its regionally- and seasonally-varying emission sources are poorly constrained. Here we employ natural abundance radiocarbon (C-14) measurements of BC intercepted at a northern Malaysia regional receptor site, Bachok, to quantify the relative biomass vs. fossil source contributions of atmospheric BC, in a first year-round study for SE Asia (December 2015-December 2016). The annual average C-14 signature suggests as large contributions from biomass burning as from fossil fuel combustion. This is similar to findings from analogous measurements at S Asian receptors sites (similar to 50% biomass burning), while E Asia sites are dominated by fossil emission (similar to 20% biomass burning). The C-14-based source fingerprinting of BC in the dry spring season in SE Asia signals an even more elevated biomass burning contribution (similar to 70% or even higher), presumably from forest, shrub and agricultural fires. This is consistent with this period showing also elevated ratio of organic carbon to BC (up from similar to 5 to 30) and estimates of BC emissions from satellite fire data. Hence, the present study emphasizes the importance of mitigating dry season vegetation fires in SE Asia.
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| 22. |
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| 23. |
- Sun, Jia-Qi, et al.
(författare)
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Spatholobus suberectus Column Extract Inhibits Estrogen Receptor Positive Breast Cancer via Suppressing ER MAPK PI3K/AKT Pathway
- 2016
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Ingår i: Evidence-based Complementary and Alternative Medicine. - : Hindawi Limited. - 1741-427X .- 1741-4288.
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Tidskriftsartikel (refereegranskat)abstract
- Although Chinese herbal compounds have long been alternatively applied for cancer treatment in China, their treatment effects have not been sufficiently investigated. The Chinese herb Spatholobus suberectus is commonly prescribed to cancer patients. HPLC analysis has shown that the main components of Spatholobus suberectus are flavonoids that can be classified as phytoestrogens, having a structure similar to estrogen. This study was designed to investigate the effects of Spatholobus suberectus column extract (SSCE) on the estrogen receptor-positive (ER+) breast cancer cell line MCF-7 and its possible molecular mechanism. In our study, MTT assay was performed to evaluate cell viability. The results show that SSCE (80, 160, and 320 mu g/ml) significantly decreased the viability of MCF-7 cells. SSCE also triggered apoptosis, arrested the cell cycle at the G0/G1 phase, and inhibited cell migration. A dual-luciferase reporter system showed that SSCE suppressed intranuclear p-ER activity; Western blot analysis confirmed the repressed expression of phosphorylated-ER alpha (p-ER alpha), ERK1/2, p-ERK1/2, AKT, p-AKT, p-mTOR, PI3K, and p-PI3K, indicating that SSCE suppressed the MAPK PI3K/AKT signaling pathway. Collectively, our results suggest that SSCE causes apoptosis, an arrest in the G0/G1 phase, and a decrease in migration in ER+ MCF-7 cells via hypoactivity of the ER and suppression of the MAPK PI3K/AKT pathway.
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| 24. |
- Sun, Xu, et al.
(författare)
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Chinese Herbal Medicine as Adjunctive Therapy to Chemotherapy for Breast Cancer : A Systematic Review and Meta-Analysis
- 2016
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Ingår i: Evidence-based Complementary and Alternative Medicine. - : Hindawi Limited. - 1741-427X .- 1741-4288.
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Forskningsöversikt (refereegranskat)abstract
- Chinese herbal medicine (CHM) has been increasingly employed during therapy for breast cancer, but its efficacy remains a matter of debate. This systematic review examined randomized controlled trials to provide a critical evaluation of this treatment. The results demonstrated that the combined use of CHM with chemotherapy may improve the immediate tumor response and reduce chemotherapy-associated adverse events. Our findings highlight the poor quality of Chinese studies, and additional well-designed randomized controlled trials addressing the role of CHM are warranted. The lack of molecular-based evidence for CHM and Zheng has resulted in a limited understanding and acceptance of CHM and traditional Chinese medicine in Western countries. We believe that researchers should immediately explore a CHM-based cure, and CHM should be applied to routine care as soon as conclusive data are available.
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| 25. |
- Wang, Bo, et al.
(författare)
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An organoid library of salivary gland tumors reveals subtype-specific characteristics and biomarkers
- 2022
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Ingår i: Journal of Experimental & Clinical Cancer Research. - : BioMed Central (BMC). - 1756-9966. ; 41:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Salivary gland tumors (SGTs) include a large group of rare neoplasms in the head and neck region, and the heterogeneous and overlapping features among the subtypes frequently make diagnostic difficulties. There is an urgent need to understand the cellular mechanisms underlying the heterogeneity and overlap among the subtypes, and explore the subtype-specific diagnostic biomarkers.Methods: The tumor tissue and the adjacent normal tissue from the 6 most common types of SGTs were processed for organoid culture which only maintained tumor epithelial cells. Organoids were histologically evaluated based on phenotype markers, followed by transcriptional profiling using RNA-sequencing. The transcriptomic similarities and differences among the subtypes were analyzed by subtype consensus clustering and hierarchical clustering. Furthermore, by comparative transcriptional analysis for these 6 types of SGTs and the matched organoids, the potential diagnostic biomarkers from tumor epithelium were identified, in which two selected biomarkers were evaluated by qPCR and confirmed by immunohistochemistry staining using a tissue microarray.Results: We generated a biobank of patient-derived organoids (PDOs) with 6 subtypes of SGTs, including 21 benign and 24 malignant SGTs. The PDOs recapitulated the morphological and transcriptional characteristics of the parental tumors. The overlap in the cell types and the heterogenous growth patterns were observed in the different subtypes of organoids. Comparing the bulk tissues, the cluster analysis of the PDOs remarkably revealed the epithelial characteristics, and visualized the intrinsic relationship among these subtypes. Finally, the exclusive biomarkers for the 6 most common types of SGTs were uncovered by comparative analysis, and PTP4A1 was demonstrated as a useful diagnostic biomarker for mucoepidermoid carcinoma.Conclusions: We established the first organoid biobank with multiple subtypes of SGTs. PDOs of SGTs recapitulate the morphological and transcriptional characteristics of the original tumors, which uncovers subtype-specific biomarkers and reveals the molecular distance among the subtype of SGTs.
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| 26. |
- Yang, Wen-Jing, et al.
(författare)
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Heparanase from triple-negative breast cancer and platelets acts as an enhancer of metastasis
- 2020
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Ingår i: International Journal of Oncology. - : SPANDIDOS PUBL LTD. - 1019-6439 .- 1791-2423. ; 57:4, s. 890-904
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Tidskriftsartikel (refereegranskat)abstract
- Triple-negative breast cancer (TNBC), which is characterized by inherently aggressive behavior and lack of recognized molecular targets for therapy, poses a serious threat to women's health worldwide. However, targeted treatments have yet to be made available. A crosstalk between tumor cells and platelets (PLT) contributing to growth, angiogenesis and metastasis has been reported in numerous cancers. Heparanase (Hpa), the only mammalian endoglycosidase that cleaves heparan sulfate, has been demonstrated to contribute to the growth, angiogenesis and metastasis of numerous cancers. Hypoxia affects the growth, angiogenesis and metastasis of nearly all solid tumors, and the ability of Hpa to promote invasion is enhanced in hypoxia. However, whether Hpa can strengthen the crosstalk between tumor cells and PLT, and whether enhancing the biological function of Hpa in TNBC promotes malignant progression, have yet to be fully elucidated. The present study, based on bioinformatics analysis and experimental studies in vivo and in vitro, demonstrated that Hpa enhanced the crosstalk between TNBC cells and PLT to increase the supply of oxygen and nutrients, while also conferring tolerance of TNBC cells to oxygen and nutrient shortage, both of which are important for overcoming the stress of hypoxia and nutritional deprivation in the tumor microenvironment, thereby promoting malignant progression, including growth, angiogenesis and metastasis in TNBC. In addition, the hypoxia-inducible factor-1a (HIF-1a)/vascular endothelial growth factor-a (VEGF- a)/phosphorylated protein kinase B (p-)Akt axis may be the key pathway involved in the effects of Hpa on the biological processes mentioned above. Therefore, improving local hypoxia, anti-Hpa treatment and inhibiting PLT activation may improve the prognosis of TNBC.
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| 27. |
- Zhang, Yi, et al.
(författare)
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Elemene inhibits the migration and invasion of 4T1 murine breast cancer cells via heparanase
- 2017
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 16:1, s. 794-800
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Tidskriftsartikel (refereegranskat)abstract
- Elemene (ELE), a natural plant drug extracted from Curcumae Rhizoma, has been widely used for cancer treatment in China for more than 20 years. Although it is reported to be a broad-spectrum anticancer drug, the mechanism underlying the action of ELE in the treatment of breast cancer remains to be fully elucidated. Heparanase, a mammalian endo-D-glucuronidase, is involved in degradation of the extracellular matrix (ECM), and thus promotes tumor progression and metastasis. The downregulation of heparanase can effectively reduce tumor malignant behaviors. In the present study, the inhibitory effects of ELE were evaluated in breast cancer cells using a Cell Counting kit 8 assay. The migratory and invasive capabilities of cancer cells were investigated using a wound healing assay, real-time cell analysis and a Transwell assay. In addition, western blot analysis was used to assess alterations in the expression levels of key proteins. The present results confirmed the antiproliferative and antimetastatic effects of ELE, using low-molecular weight heparin (LMWH) as a positive control. In addition, ELE was demonstrated to downregulate the expression of heparanase, and decrease the phosphorylation of extracellular signal-regulated kinase and AKT. These findings suggested that ELE may be a promising agent targeting heparanase in the treatment of breast cancer.
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| 28. |
- Zhang, Yi, et al.
(författare)
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Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways
- 2017
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 22:5
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Tidskriftsartikel (refereegranskat)abstract
- Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways.
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| 29. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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