| 1. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
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| 3. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
-
In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
-
Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 9. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 10. |
-
- 2019
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Journal article (peer-reviewed)
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| 11. |
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| 12. |
- Fang, Evandro F., et al.
(author)
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A research agenda for ageing in China in the 21st century (2nd edition): Focusing on basic and translational research, long-term care, policy and social networks.
- 2020
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In: Ageing Research Reviews. - : Elsevier BV. - 1568-1637. ; 64
-
Journal article (peer-reviewed)abstract
- One of the key issues facing public healthcare is the global trend of an increasingly ageing society which continues to present policy makers and caregivers with formidable healthcare and socio-economic challenges. Ageing is the primary contributor to a broad spectrum of chronic disorders all associated with a lower quality of life in the elderly. In 2019, the Chinese population constituted 18 % of the world population, with 164.5 million Chinese citizens aged 65 and above (65+), and 26 million aged 80 or above (80+). China has become an ageing society, and as it continues to age it will continue to exacerbate the burden borne by current family and public healthcare systems. Major healthcare challenges involved with caring for the elderly in China include the management of chronic non-communicable diseases (CNCDs), physical frailty, neurodegenerative diseases, cardiovascular diseases, with emerging challenges such as providing sufficient dental care, combating the rising prevalence of sexually transmitted diseases among nursing home communities, providing support for increased incidences of immune diseases, and the growing necessity to provide palliative care for the elderly. At the governmental level, it is necessary to make long-term strategic plans to respond to the pressures of an ageing society, especially to establish a nationwide, affordable, annual health check system to facilitate early diagnosis and provide access to affordable treatments. China has begun work on several activities to address these issues including the recent completion of the of the Ten-year Health-Care Reform project, the implementation of the Healthy China 2030 Action Plan, and the opening of the National Clinical Research Center for Geriatric Disorders. There are also societal challenges, namely the shift from an extended family system in which the younger provide home care for their elderly family members, to the current trend in which young people are increasingly migrating towards major cities for work, increasing reliance on nursing homes to compensate, especially following the outcomes of the ‘one child policy’ and the ‘empty-nest elderly’ phenomenon. At the individual level, it is important to provide avenues for people to seek and improve their own knowledge of health and disease, to encourage them to seek medical check-ups to prevent/manage illness, and to find ways to promote modifiable health-related behaviors (social activity, exercise, healthy diets, reasonable diet supplements) to enable healthier, happier, longer, and more productive lives in the elderly. Finally, at the technological or treatment level, there is a focus on modern technologies to counteract the negative effects of ageing. Researchers are striving to produce drugs that can mimic the effects of ‘exercising more, eating less’, while other anti-ageing molecules from molecular gerontologists could help to improve ‘healthspan’ in the elderly. Machine learning, ‘Big Data’, and other novel technologies can also be used to monitor disease patterns at the population level and may be used to inform policy design in the future. Collectively, synergies across disciplines on policies, geriatric care, drug development, personal awareness, the use of big data, machine learning and personalized medicine will transform China into a country that enables the most for its elderly, maximizing and celebrating their longevity in the coming decades. This is the 2nd edition of the review paper (Fang EF et al., Ageing Re. Rev. 2015).
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| 13. |
- Fu, Hong, et al.
(author)
-
Energetic Asymmetry Connected with Energy Flow Changes in Response to Eutrophication : A Study of Multiple Fish Species in Subtropical Shallow Lakes
- 2019
-
In: Polish Journal of Ecology. - 1505-2249. ; 67:4, s. 305-315
-
Journal article (peer-reviewed)abstract
- Energy flow is a central characteristic in all ecosystems, and it has attracted considerable scientific attention due to its significant effects on the stability of food webs. Lake ecosystems that undergo regime shifts (clear water phase, phytoplankton dominated changed into turbid water, macrophytes dominated or vice versa) are characterized by a series of transformation in trophic structure. Although previous studies have mainly focused on the causes and consequences of regime shifts in shallow lakes, studies about responses of energy flow changes to regime shifts is far from complete. In this paper, we estimated trophic position and benthivory (i.e. degree of benthivory) of seventeen fish species from seven shallow lakes. Our data show that the trophic position and benthivory of fish species in clear water phase are significantly higher than in turbid water. This finding might help spark some ideas for subtropical lake eutrophication treatment.
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| 14. |
- He, J. L., et al.
(author)
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Slow light in a dielectric waveguide with negative-refractive-index photonic crystal cladding
- 2008
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In: Optics Express. - 1094-4087. ; 16:15, s. 11077-11082
-
Journal article (peer-reviewed)abstract
- A slow light waveguide made of a dielectric slab inserted in a two-dimensional photonic crystal with a negative effective refractive index is proposed and numerically studied. The waveguide may possess modes with zero group velocity, and its frequency varies with the thickness of the waveguide. A linearly tapered left-handed photonic crystal waveguide is also proposed and studied. It is shown that the so-called 'trapped rainbow' proposed by Tsakmakidis, Boardman, and Hess [1] is difficult to realize due to a coupling of forward- and backward-propagating modes near zero group velocity. However, different frequency components of a broadband excitation can still be separated through partial accumulation at waveguide sections of different thicknesses.
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| 15. |
- He, Shu-Lan, et al.
(author)
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Mitochondrial-related gene expression profiles suggest an important role of PGC-1alpha in the compensatory mechanism of endemic dilated cardiomyopathy.
- 2013
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In: Experimental Cell Research. - : Elsevier. - 0014-4827 .- 1090-2422. ; 319:17, s. 2604-2616
-
Journal article (peer-reviewed)abstract
- Keshan disease (KD) is an endemic dilated cardiomyopathy with unclear etiology. In this study, we compared mitochondrial-related gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from 16 KD patients and 16 normal controls in KD areas. Total RNA was isolated, amplified, labeled and hybridized to Agilent human 4 × 44k whole genome microarrays. Mitochondrial-related genes were screened out by the Third-Generation Human Mitochondria-Focused cDNA Microarray (hMitChip3). Quantitative real-time PCR, immunohistochemical and biochemical parameters related mitochondrial metabolism were conducted to validate our microarray results. In KD samples, 34 up-regulated genes (ratios ≥ 2.0) were detected by significance analysis of microarrays and ingenuity systems pathway analysis (IPA). The highest ranked molecular and cellular functions of the differentially regulated genes were closely related to amino acid metabolism, free radical scavenging, carbohydrate metabolism, and energy production. Using IPA, 40 significant pathways and four significant networks, involved mainly in apoptosis, mitochondrion dysfunction, and nuclear receptor signaling were identified. Based on our results, we suggest that PGC-1alpha regulated energy metabolism and anti-apoptosis might play an important role in the compensatory mechanism of KD. Our results may lead to the identification of potential diagnostic biomarkers for KD in PBMCs, and may help to understand the pathogenesis of KD.
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| 16. |
- Hong, Xuezhi, et al.
(author)
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Linearly interpolated sub-symbol optical phase noise suppression in CO-OFDM system
- 2015
-
In: Optics Express. - 1094-4087. ; 23:4, s. 4691-4702
-
Journal article (peer-reviewed)abstract
- An optical phase noise suppression algorithm, LI-SCPEC, based on phase linear interpolation and sub-symbol processing is proposed for CO-OFDM system. By increasing the temporal resolution of carrier phase tracking through dividing one symbol into several sub-blocks, i.e., sub-symbols, inter-carrier-interference (ICI) mitigation is achieved in the proposed algorithm. Linear interpolation is employed to obtain a reliable temporal reference for sub-symbol phase estimation. The new algorithm, with only a few number of sub-symbols (N-B = 4), can provide a considerably larger laser linewidth tolerance than several other ICI mitigation algorithms as demonstrated by Monte-Carlo simulations. Numerical analysis verifies that the best performance is achieved with an optimal and moderate number of sub-symbols. Complexity analysis shows that the required number of complex-valued multiplications is independent of the number of sub-symbols used in the proposed algorithm. (C) 2015 Optical Society of America
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| 17. |
- Hong, Xuezhi, et al.
(author)
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Low-complexity linewidth-tolerant time domain sub-symbol optical phase noise suppression in CO-OFDM systems
- 2016
-
In: Optics Express. - 1094-4087. ; 24:5, s. 4856-4871
-
Journal article (peer-reviewed)abstract
- Two linewidth-tolerant optical phase noise suppression algorithms, non-decision aided sub-symbol optical phase noise suppression (NDA-SPS) and partial-decision aided sub-symbol optical phase noise suppression (PDA-SPS), based on low-complexity time domain sub-symbol processing are proposed for coherent optical orthogonal frequency division multiplexing (CO-OFDM) systems. High accuracy carrier phase estimation is achieved in the NDA-SPS algorithm without decision error propagation. Compared with NDA-SPS, partial-decision aided estimation is introduced in PDA-SPS to reduce the pilot-overhead by half, yet only a small performance degradation is induced. The principles and computational complexities of the proposed algorithms are theoretically analyzed. By adopting specially designed comb-type pilot subcarriers, multiplier-free observation-based matrix generation is realized in the proposed algorithms. Computationally intensive discrete Fourier transform (DFT) or inverse DFT (IDFT) operations, which are usually carried out in other high-performance inter-carrier-interference (ICI) mitigation algorithms multiple times, are completely avoided. Compared with several other sub-symbol algorithms, the proposed algorithms with lower complexities offer considerably larger laser linewidth tolerances as demonstrated by Monte-Carlo simulations. Numerical analysis verifies that the optimal performance of PDA-SPS can be achieved with moderate numbers of sub-symbols.
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| 18. |
- Hong, Xiaojian, et al.
(author)
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Low-complexity optical phase noise suppression in CO-OFDM system using recursive principal components elimination
- 2015
-
In: Optics Express. - 1094-4087. ; 23:18, s. 24077-24087
-
Journal article (peer-reviewed)abstract
- A low-complexity optical phase noise suppression approach based on recursive principal components elimination, R-PCE, is proposed and theoretically derived for CO-OFDM systems. Through frequency domain principal components estimation and elimination, signal distortion caused by optical phase noise is mitigated by R-PCE. Since matrix inversion and domain transformation are completely avoided, compared with the case of the orthogonal basis expansion algorithm (L = 3) that offers a similar laser linewidth tolerance, the computational complexities of multiple principal components estimation are drastically reduced in the R-PCE by factors of about 7 and 5 for q = 3 and 4, respectively. The feasibility of optical phase noise suppression with the R-PCE and its decision-aided version (DA-R-PCE) in the QPSK/16QAM CO-OFDM system are demonstrated by Monte-Carlo simulations, which verify that R-PCE with only a few number of principal components q (= 3) provides a significantly larger laser linewidth tolerance than conventional algorithms, including the common phase error compensation algorithm and linear interpolation algorithm. Numerical results show that the optimal performance of R-PCE and DA-R-PCE can be achieved with a moderate q, which is beneficial for low-complexity hardware implementation.
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| 19. |
- Hong, Yuanyuan, et al.
(author)
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Elastic all-optical multi-hop interconnection in data centers with adaptive spectrum allocation
- 2017
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In: Optics Communications. - : Elsevier. - 0030-4018 .- 1873-0310. ; 383, s. 478-484
-
Journal article (peer-reviewed)abstract
- In this paper, a novel flex-grid all-optical interconnect scheme that supports transparent multi-hop connections in data centers is proposed. An inter-rack all-optical multi-hop connection is realized with an optical loop employed at flex-grid wavelength selective switches (WSSs) in an intermediate rack rather than by relaying through optical-electric-optical (O-E-O) conversions. Compared with the conventional O-E-O based approach, the proposed all-optical scheme is able to off-load the traffic at intermediate racks, leading to a reduction of the power consumption and cost. The transmission performance of the proposed flex-grid multi-hop all-optical interconnect scheme with various modulation formats, including both coherently detected and directly detected approaches, are investigated by Monte-Carlo simulations. To enhance the spectrum efficiency (SE), number-of-hop adaptive bandwidth allocation is introduced. Numerical results show that the SE can be improved by up to 33.3% at 40 Gbps, and by up to 25% at 100 Gbps. The impact of parameters, such as targeted bit error rate (BER) level and insertion loss of components, on the transmission performance of the proposed approach are also explored. The results show that the maximum SE improvement of the adaptive approach over the non-adaptive one is enhanced with the decrease of the targeted BER levels and the component insertion loss.
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| 20. |
- Hong, Y., et al.
(author)
-
Flex-grid all-optical interconnect supporting transparent multi-hop connection in data centers
- 2015
-
Conference paper (peer-reviewed)abstract
- In this paper a novel flex-grid all-optical interconnect scheme is proposed for data center, where a transparent multi-hop connection can be realized by using optical bypass rather than going through optical-electric-optical conversions, enhancing energy efficiency for inter-rack communications. Moreover, elastic spectrum allocation is adopted in the proposed scheme to increase the resource utilization and scalability. Transmission performance evaluation has been carried out to verify the feasibility of the proposed scheme.
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| 21. |
- Hong, Yuanyuan, et al.
(author)
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Hybrid Routing and Adaptive Spectrum Allocation for Flex-Grid Optical Interconnects
- 2018
-
In: Journal of Optical Communications and Networking. - : Optical Society of America. - 1943-0620 .- 1943-0639. ; 10:5, s. 506-514
-
Journal article (peer-reviewed)abstract
- A hybrid routing scheme with an adaptive spectrum assignment is proposed for flex-grid all-optical core switch supporting multihop transparent paths in data center networks. Compared with conventional spectrum assignment algorithms (RSA) developed for a multihop network with optical-electric-optical (OEO) conversion in every hop (i.e., RSA for EO) and that devised for an all-optical multihop network (i.e., RSA for AO), the present RSA algorithm provides better utilization of network resources. Being aware of the all-optical bypass path in hopping, the proposed RSA reduces the blocking probability due to lack of bandwidth-tunable transceivers, which is the major reason for blocking for an RSA for the EO. Similar to the RSA for the AO, the proposed RSA is compatible with the number-of-hops adaptive spectrum assignment, which improves spectrum efficiency. On the other hand, the new algorithm enhances connectivity by eliminating the number-of-hops limitation, which severely constrains the performance of RSA for the AO. Simulations for the system are carried out to investigate the performance of the new algorithm. The impacts of various parameters, such as traffic load, ratio of connection requests with different data rates, and resource configuration on the link cost, are studied in terms of network blocking probability (BP). The achievable traffic load of the proposed RSA under varied connection degrees (i.e., the maximum number of ports that one rack has in order to connect to the core switch) and number of racks is also assessed to keep BP no more than 0.1. The results show that the proposed RSA with appropriate cost functions outperforms the EO and AO, which implies that it has the highest scalability.
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| 22. |
- Jin, Zhichao, et al.
(author)
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A retrospective survey of research design and statistical analyses in selected Chinese medical journals in 1998 and 2008
- 2010
-
In: PLOS ONE. - : PLOS. - 1932-6203. ; 5:5
-
Journal article (peer-reviewed)abstract
- BACKGROUND: High quality clinical research not only requires advanced professional knowledge, but also needs sound study design and correct statistical analyses. The number of clinical research articles published in Chinese medical journals has increased immensely in the past decade, but study design quality and statistical analyses have remained suboptimal. The aim of this investigation was to gather evidence on the quality of study design and statistical analyses in clinical researches conducted in China for the first decade of the new millennium.METHODOLOGY/PRINCIPAL FINDINGS: Ten (10) leading Chinese medical journals were selected and all original articles published in 1998 (N = 1,335) and 2008 (N = 1,578) were thoroughly categorized and reviewed. A well-defined and validated checklist on study design, statistical analyses, results presentation, and interpretation was used for review and evaluation. Main outcomes were the frequencies of different types of study design, error/defect proportion in design and statistical analyses, and implementation of CONSORT in randomized clinical trials. From 1998 to 2008: The error/defect proportion in statistical analyses decreased significantly ( = 12.03, p<0.001), 59.8% (545/1,335) in 1998 compared to 52.2% (664/1,578) in 2008. The overall error/defect proportion of study design also decreased ( = 21.22, p<0.001), 50.9% (680/1,335) compared to 42.40% (669/1,578). In 2008, design with randomized clinical trials remained low in single digit (3.8%, 60/1,578) with two-third showed poor results reporting (defects in 44 papers, 73.3%). Nearly half of the published studies were retrospective in nature, 49.3% (658/1,335) in 1998 compared to 48.2% (761/1,578) in 2008. Decreases in defect proportions were observed in both results presentation ( = 93.26, p<0.001), 92.7% (945/1,019) compared to 78.2% (1023/1,309) and interpretation ( = 27.26, p<0.001), 9.7% (99/1,019) compared to 4.3% (56/1,309), some serious ones persisted.CONCLUSIONS/SIGNIFICANCE: Chinese medical research seems to have made significant progress regarding statistical analyses, but there remains ample room for improvement regarding study designs. Retrospective clinical studies are the most often used design, whereas randomized clinical trials are rare and often show methodological weaknesses. Urgent implementation of the CONSORT statement is imperative.
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| 23. |
- Kato, Norihiro, et al.
(author)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
-
Journal article (peer-reviewed)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 24. |
- Klionsky, Daniel J., et al.
(author)
-
Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
-
In: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
-
Research review (peer-reviewed)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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| 25. |
- Kristan, Matej, et al.
(author)
-
The Visual Object Tracking VOT2015 challenge results
- 2015
-
In: Proceedings 2015 IEEE International Conference on Computer Vision Workshops ICCVW 2015. - : IEEE. - 9780769557205 ; , s. 564-586
-
Conference paper (peer-reviewed)abstract
- The Visual Object Tracking challenge 2015, VOT2015, aims at comparing short-term single-object visual trackers that do not apply pre-learned models of object appearance. Results of 62 trackers are presented. The number of tested trackers makes VOT 2015 the largest benchmark on short-term tracking to date. For each participating tracker, a short description is provided in the appendix. Features of the VOT2015 challenge that go beyond its VOT2014 predecessor are: (i) a new VOT2015 dataset twice as large as in VOT2014 with full annotation of targets by rotated bounding boxes and per-frame attribute, (ii) extensions of the VOT2014 evaluation methodology by introduction of a new performance measure. The dataset, the evaluation kit as well as the results are publicly available at the challenge website(1).
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| 26. |
- Li, He, et al.
(author)
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Enhanced production of trehalose in Escherichia coli by homologous expression of otsBA in the presence of the trehalase inhibitor, validamycin A, at high osmolarity
- 2012
-
In: Journal of Bioscience and Bioengineering. - : Elsevier. - 1389-1723 .- 1347-4421. ; 113:2, s. 224-232
-
Journal article (peer-reviewed)abstract
- Trehalose production in Escherichia coli DH5α was explored by overexpressing otsBA operon encoding trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase. Production and subsequent degradation of trehalose resulted in low production of trehalose in engineered cells overexpressing otsBA, which was primarily due to the concomitant expression of endogenous trehalase. Through an in vitro enzyme assay and flask cultures of engineered cells, trehalase expression was shown to be directly related to the expression of otsBA rather than osmotic stress. Validamycin A effectively inhibited E. coli trehalase and the intracellular accumulation of trehalose was markedly enhanced in the presence of validamycin A at an optimal concentration in the medium. The trehalose production was further increased upon growth in a hypertonic medium in the presence of validamycin A, with most trehalose accumulating as an intracellular product. The highest titer was obtained when otsBA expression was induced by a medium-copy vector, ptrc99A, with 0.5mM of isopropyl β-d-1-thiogalactopyranoside. Trehalose titer was 1.7 g/L in controlled bioreactor cultures using synthetic M9 medium supplemented with 40 g/L glycerol, 0.1mM validamycin A, and 300 mM NaCl.
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| 27. |
- Luo, Zhong-Zhen, et al.
(author)
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PbGa2MSe6 (M = Si, Ge) : Two Exceptional Infrared Nonlinear Optical Crystals
- 2015
-
In: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 27:3, s. 914-922
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Journal article (peer-reviewed)abstract
- Two noncentrosymmetric (NCS) quaternary selenides, PbGa2SiSe6 (1) and PbGa2GeSe6 (2), with second-order nonlinear optical (NLO) responses, were synthesized by a conventional high-temperature solid-state reaction method. Compounds 1 and 2 are constructed by three NCS chromophores, [PbSe4], [GaSe4], and [Ga/SiSe4] or [Ga/GeSe4], with the covalent interactions between the X and Se atoms (X = Pb, Ga, Ga/Si, or Ga/Ge). They crystallize in the polar space groups Cc and Fdd2, respectively. Inspiringly, compound 2 is phase-matchable (PM) and shows high laser-induced damage threshold (LIDT) of 3.7 x AgGaS2 and wide transparent region (0.6325 mu m) in the mid-infrared (MIR) region. Most importantly, it presents extraordinary strong second harmonic generation (SHG) at 2.05 mu m radiation of about 12 x AgGaS2 at the particle size of 2545 mu m, which represents the strongest SHG among PM chalcogenides to date. The calculated major SHG tensor elements of compounds 1 and 2 are d31 = 224.7 and d12 = 222.1 pm/V, respectively, while the calculated d36 of AgGaS2 is only 21.2 pm/V.
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| 28. |
- Menden, MP, et al.
(author)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Journal article (peer-reviewed)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 29. |
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| 30. |
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| 31. |
- Schuettpelz, Eric, et al.
(author)
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A community-derived classification for extant lycophytes and ferns
- 2016
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In: Journal of Systematics and Evolution. - : Wiley. - 1674-4918 .- 1759-6831. ; 54:6, s. 563-603
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Journal article (peer-reviewed)abstract
- Phylogeny has long informed pteridophyte classification. As our ability to infer evolutionary trees has improved, classifications aimed at recognizing natural groups have become increasingly predictive and stable. Here, we provide a modern, comprehensive classification for lycophytes and ferns, down to the genus level, utilizing a community-based approach. We use monophyly as the primary criterion for the recognition of taxa, but also aim to preserve existing taxa and circumscriptions that are both widely accepted and consistent with our understanding of pteridophyte phylogeny. In total, this classification treats an estimated 11 916 species in 337 genera, 51 families, 14 orders, and two classes. This classification is not intended as the final word on lycophyte and fern taxonomy, but rather a summary statement of current hypotheses, derived from the best available data and shaped by those most familiar with the plants in question. We hope that it will serve as a resource for those wanting references to the recent literature on pteridophyte phylogeny and classification, a framework for guiding future investigations, and a stimulus to further discourse.
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| 32. |
- Tian, Jiahan, et al.
(author)
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Wide-field-of-view auto-coupling optical antenna system for high-speed bidirectional optical wireless communications in C band
- 2023
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In: Optics Express. - : Optica Publishing Group. - 1094-4087. ; 31:20, s. 33435-33448
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Journal article (peer-reviewed)abstract
- Due to a great many superior features of infrared light communication (ILC), like high capacity and strong privacy, ILC is considered a potential candidate for serving the high demands of beyond fifth-generation/sixth-generation (B5G/6 G) communication systems. However, the terminal's limited field-of-view (FOV) induces great difficulty in establishing line-of-sight (LoS) link between the transceiver and the terminal. In this paper, we propose a wide-FOV auto-coupling optical antenna system that utilizes a wide-FOV telecentric lens to collect incident infrared beams and automatically couple them into a specific single-mode-fiber (SMF) channel of fiber array and optical switch. The performance of this optical antenna system is assessed through simulation and manual alignment operation, and validated by automatic alignment results. A coupling loss of less than 10.6 dB within a FOV of 100(degrees )for both downstream and upstream beams in C band is demonstrated by the designed system. Furthermore, we establish a bidirectional optical wireless communications (OWC) system employing this antenna and a fiber-type modulating retro-reflector (MRR) system in the terminal. Both 10-Gbps on-off keying (OOK) downstream and upstream transmissions are successfully realized with the FOV of up to 100(degrees) in C band where the measured bit-error-rate (BER) is lower than 3.8 x 10-3. To the best of our knowledge, this is a brand-new auto-coupling optical antenna system with the largest FOV in ILC automatic alignment works in terminals that have ever been reported.
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| 33. |
- Tian, Jiahan, et al.
(author)
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Wide-Field-of-View Modulating Retro-Reflector System Based on a Telecentric Lens for High-Speed Free-Space Optical Communication
- 2023
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In: IEEE Photonics Journal. - : Institute of Electrical and Electronics Engineers (IEEE). - 1943-0655. ; 15:5
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Journal article (peer-reviewed)abstract
- Modulating retro-reflector (MRR) free-space optical (FSO) communication technology presents a bright future for realizing the small size, weight, and power (SWaP) design of one end of the optical link, facilitating the further application of the FSO communication to the small platforms. However, the limited field-of-view (FOV) of MRR impedes its wide employment. In this article, a novel wide-FOV MRR using an image space telecentric lens is proposed and a bidirectional FSO communication system is experimentally demonstrated using this MRR with a single light source. The performance of the telecentric lens between the transceiver and terminal is assessed by simulation and also validated by experimental results, with a coupling loss less than 9.1 dB within a FOV of 110 degrees. Both 10-Gbit/s on-off keying (OOK) downstream and upstream signals for free space communication at different incident angles are successfully realized using this designed wide-FOV MRR. The experimental results validate the proposed MRR has a FOV of up to 110 degrees where the measured bit error rate (BER) is lower than 3.8 x 10-3 for both downstream and upstream signals. To the best of our knowledge, this is the largest FOV ever reported for MRRs in high-speed bidirectional FSO communication systems.
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| 34. |
- Wang, Zhaoming, et al.
(author)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 35. |
- Yang, Xu-Fang, et al.
(author)
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High efficient isolation and systematic identification of human adipose-derived mesenchymal stem cells
- 2011
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In: Journal of Biomedical Science. - : Springer Science and Business Media LLC. - 1021-7770 .- 1423-0127. ; 18, s. 59-
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Journal article (peer-reviewed)abstract
- Background: Developing efficient methods to isolate and identify human adipose-derived mesenchymal stem cells (hADSCs) remains to be one of the major challenges in tissue engineering. Methods: We demonstrate here a method by isolating hADSCs from abdominal subcutaneous adipose tissue harvested during caesarian section. The hADSCs were isolated from human adipose tissue by collagenase digestion and adherence to flasks. Results: The yield reached around 1 x 10(6) hADSCs per gram adipose tissue. The following comprehensive identification and characterization illustrated pronounced features of mesenchymal stem cells (MSCs). The fibroblast-like hADSCs exhibited typical ultrastructure details for vigorous cell activities. Karyotype mapping showed normal human chromosome. With unique immunophenotypes they were positive for CD29, CD44, CD73, CD105 and CD166, but negative for CD31, CD34, CD45 and HLA-DR. The growth curve and cell cycle analysis revealed high capability for self-renewal and proliferation. Moreover, these cells could be functionally induced into adipocytes, osteoblasts, and endothelial cells in the presence of appropriate conditioned media. Conclusion: The data presented here suggest that we have developed high efficient isolation and cultivation methods with a systematic strategy for identification and characterization of hADSCs. These techniques will be able to provide safe and stable seeding cells for research and clinical application.
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| 36. |
- Aad, G., et al.
(author)
-
- 2012
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Journal article (peer-reviewed)
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| 37. |
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| 38. |
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Abou Ghayda, Ramy, et al.
(author)
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The global case fatality rate of coronavirus disease 2019 by continents and national income: A meta-analysis
- 2022
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In: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 94:6, s. 2402-2413
-
Journal article (peer-reviewed)abstract
- The aim of this study is to provide a more accurate representation of COVID-19s case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.
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| 48. |
- Adare, A, et al.
(author)
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Azimuthal-Angle Dependence of Charged-Pion-Interferometry Measurements with Respect to Second- and Third-Order Event Planes in Au+Au Collisions at sqrt[s_{NN}]=200 GeV.
- 2014
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In: Physical Review Letters. - 1079-7114. ; 112:22
-
Journal article (peer-reviewed)abstract
- Charged-pion-interferometry measurements were made with respect to the second- and third-order event plane for Au+Au collisions at sqrt[s_{NN}]=200 GeV. A strong azimuthal-angle dependence of the extracted Gaussian-source radii was observed with respect to both the second- and third-order event planes. The results for the second-order dependence indicate that the initial eccentricity is reduced during the medium evolution, which is consistent with previous results. In contrast, the results for the third-order dependence indicate that the initial triangular shape is significantly reduced and potentially reversed by the end of the medium evolution, and that the third-order oscillations are largely dominated by the dynamical effects from triangular flow.
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| 49. |
- Adare, A., et al.
(author)
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Azimuthal anisotropy of pi(0) and eta mesons in Au plus Au collisions at root s(NN)=200 GeV
- 2013
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 88:6
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Journal article (peer-reviewed)abstract
- The azimuthal anisotropy coefficients v2 and v4 of p 0 and. mesons are measured in Au + Au collisions at root s(NN) = 200 GeV as a function of transverse momentum p(T) (1-14 GeV/c) and centrality. The extracted v(2) coefficients are found to be consistent between the two meson species over the measured p(T) range. The ratio of v(4)/v(2)(2) for pi(0) mesons is found to be independent of p(T) for 1- 9 GeV/c, implying a lack of sensitivity of the ratio to the change of underlying physics with p(T). Furthermore, the ratio of v(4)/v(2)(2) is systematically larger in central collisions, which may reflect the combined effects of fluctuations in the initial collision geometry and finite viscosity in the evolving medium.
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| 50. |
- Adare, A., et al.
(author)
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Azimuthal Anisotropy of pi(0) Production in Au plus Au Collisions at root s(NN)=200 GeV: Path-Length Dependence of Jet Quenching and the Role of Initial Geometry
- 2010
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In: Physical Review Letters. - 1079-7114. ; 105:14
-
Journal article (peer-reviewed)abstract
- We have measured the azimuthal anisotropy of pi(0) production for 1 < p(T) < 18 GeV/c for Au + Au collisions at root s(NN) = 200 GeV. The observed anisotropy shows a gradual decrease for 3 less than or similar to p(T) less than or similar to 7-10 GeV/c, but remains positive beyond 10 GeV/c. The magnitude of this anisotropy is underpredicted, up to at least similar to 10 GeV/c, by current perturbative QCD (PQCD) energy-loss model calculations. An estimate of the increase in anisotropy expected from initial-geometry modification due to gluon saturation effects and fluctuations is insufficient to account for this discrepancy. Calculations that implement a path-length dependence steeper than what is implied by current PQCD energy-loss models show reasonable agreement with the data.
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