1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)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. |
- Fang, Aoqi, et al.
(författare)
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High Color Conversion Efficiency Realized in Graphene-Connected Nanorod Micro-LEDs Using Hybrid Ag Nanoparticles and Quantum Dots
- 2024
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Ingår i: Advanced Optical Materials. - 2195-1071. ; 12:19
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, a uniform nanorod (NR) array is etched onto the surface of Micro-Light-Emitting-Diodes (µLEDs) and mix Ag nanoparticles (NPs) with QDs to fill the gaps between the nanorods. Simultaneously, the study utilizes graphene to connect individual nanorods and enhance current spreading. The nanorod array's structure significantly reduces the distance between the QDs and the quantum well (QW), reducing energy loss from the excitation light source through a non-radiative energy transfer (NRET) mechanism. Additionally, the Ag NPs function as localized surface plasmons (LSPs), further enhancing the CCE of QDs via the absorption resonance. In this study, the effects of two types of Ag NPs are compared with different absorption resonance peaks on device performance. The results demonstrate that Ag NPs with absorption resonance peaks matching the emission wavelength of QDs play a more crucial role in the system. This configuration achieves a CCE of 77.78% for µLEDs with nanorod arrays, operating at a current of 10 mA. Compared to the conventional µLED structure with QDs only on the surface, the proposed method improves the CCE of µLEDs by an impressive 86.5%. This outcome underscores the significant contribution of the NR structure and LSPs in enhancing the CCE of QD-µLEDs.
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4. |
- Jin, Ying-Hui, et al.
(författare)
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Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
- 2020
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Ingår i: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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5. |
- Qin, Tao, et al.
(författare)
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Efficient Synthesis of Angular Selective Surfaces Based on Accurate Equivalent Circuit Analysis
- 2023
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Ingår i: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480. ; 71:6, s. 2625-2638
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Tidskriftsartikel (refereegranskat)abstract
- A new efficient synthesis method of angular selective surfaces (ASSs) based on the accurate equivalent circuit model is proposed. The angular dispersion of different components under oblique incidence is modeled by virtual lumped elements in the angular domain. The processes of obtaining the equivalent circuit for substrates, electrically small grids and patch arrays are presented in detail. The synthesized circuits are simple and accurate. Full-wave simulations are carried out to obtain the angular dispersion of different structures, and the calculated results are in good agreement with those of the equivalent circuit. A third-order ASS with bandpass response and a second-order ASS with a tunable bandwidth are given as design examples. The implemented second-order ASS shows the 0.33 to 0.52 tunable bandwidth in the angular domain. The transmission loss is better than 1.2 dB when the incidence angle is 65°-77°. The simulation results and calculated results are in good agreement with the measured results.
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6. |
- Zhang, Linyu, et al.
(författare)
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miR-125b promotes tau phosphorylation by targeting the neural cell adhesion molecule in neuropathological progression
- 2019
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Ingår i: Neurobiology of Aging. - : ELSEVIER SCIENCE INC. - 0197-4580 .- 1558-1497. ; 73, s. 41-49
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs, small noncoding RNAs, not only regulate gene expression at the post-transcriptional level in a variety of physiological processes but also accompany the initiation and progression of a vast number of diseases, including dementia. While miR-125b has been shown to be aberrantly expressed in some dementia patients, its role in the pathological process remains ambiguous. Presenilin-1/2 conditional double knockout mice exhibit a range of symptoms, including impaired cognition and memory, increased tau phosphorylation, neuroinflammation, and apoptosis, and are therefore regarded as a useful dementia model. In the prefrontal cortices of double knockout mice, miR-125b was found to be abnormally increased in an age-dependent manner. We further verified the neural cell adhesion molecule (NCAM) as an miR-125b target using the dual luciferase reporter assay. The NCAM protein level was decreased when miR-125b was overexpressed (OE) in neuronal growth factor-induced differentiated PC12 cells, which further inhibited the neuronal growth factor-induced phosphorylation of glycogen synthase kinase 3 beta (GSK beta) at the Ser9 site and ultimately increased the GSK3 beta activity and tau phosphorylation. Moreover, on serum deprivation, high GSK3 beta activity in differentiated miR-125b-OE PC12 cells induced increased caspase-3 activation. Finally, adeno-associated virus-mediated miR-125b overexpression in the prefrontal cortexes of wild-type C57B/L6 mice resulted in decreased dendritic spine density. In addition, similar to the in vitro data, elevated GSK3 beta activity and hyperphosphorylation of the tau protein were confirmed. Taken together, our findings reveal a direct regulation of miR-125b on NCAM, which leads to further effects on downstream GSK3 beta activity and tau phosphorylation and may contribute to the generation of neurofibrillary tangles in neuropathological progression.
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7. |
- Fang, Mei, et al.
(författare)
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Tuning room temperature ferromagnetism of 'in-situ' inkjet printed Fe-doped ZnO films
- 2019
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Ingår i: Semiconductor Science and Technology. - : IOP PUBLISHING LTD. - 0268-1242 .- 1361-6641. ; 34:5
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Tidskriftsartikel (refereegranskat)abstract
- ZnO is a wide-band gap semiconductor widely used in optical and electric devices, associating with ferromagnetism at low dimension endowing its possibility for functional applications with magneto-optical and magneto-electric properties. We prepared ZnO and Fe-doped ZnO thin films 'in-situ' on substrate by inkjet printing, and tuned the room temperature ferromagnetism (RTFM) of the film by Fe-doping concentration, film thickness and post annealing temperature. It was found that by Fe doping the saturation magnetization (M-s) of the film can be enhanced by more than 4 folds comparing with the un-doped film, i.e. from 0.9 emu g(-1) for the ZnO film to 3.8 emu g(-1) for the Fe-doped ZnO film with comparable thickness. The enhancement was attributed to the introduction of un-paired 3d electrons which formed long range ferromagnetic ordering, as well as the consequent structure changes with smaller grains which increased the interface induced magnetism. By changing the annealing temperature and the film thickness, the defect-induced ferromagnetism was investigated. The RTFM shows thickness dependence with peak saturation magnetization value of 4.44 emu g(-1) for the 45 nm thick film. The work provides an effective way of tuning magnetism in ZnO based films for functional device applications.
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8. |
- Guo, Junji, et al.
(författare)
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Prominent Electrochromism Achieved Using Aluminum Ion Insertion/Extraction in Amorphous WO3 Films
- 2018
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 122:33, s. 19037-19043
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Tidskriftsartikel (refereegranskat)abstract
- Although monovalent lithium has been successfully used as a coloring ion in electrochromic applications, it still faces the challenges of low safety, high cost, and limited reserves. Herein, we demonstrate that the amorphous WO3 films intercalated with Al3+ ions could exhibit desired wide optical modulation (similar to 63.0%) and high coloration efficiency (similar to 72.0 cm(2) A(-1), which is >100% higher than that with Li+ or Na+), benefiting from the three-electron redox properties of aluminum. Due to the strong electrostatic force and large atomic weight, the charge exchange processes for Al3+ ions are limited only to the near-surface region and consequently bring about enhanced electrochromic stability. Our findings provide in-depth insights into the nature of electrochromism and also open up a new route toward scalable electrochromic devices using sputtering techniques and earth-abundant materials.
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9. |
- Guo, Junji, et al.
(författare)
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Vacancy dependent electrochromic behaviors of NiOx anodes : As a single layer and in devices
- 2018
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Ingår i: Solar Energy Materials and Solar Cells. - : ELSEVIER SCIENCE BV. - 0927-0248 .- 1879-3398. ; 178, s. 193-199
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Tidskriftsartikel (refereegranskat)abstract
- Electrochromic(EC), nonstoichiometric NiOx thin films were made by reactive magnetron sputtering at low oxygen flow ratio(i.e., P = O-2/Ar + O-2 < 10%). The results of optical spectral, x-ray diffraction spectrum, and x-ray photoelectron spectroscopy analyses indicate that the samples are oxygen(nickel)-deficient as P <= %4(>=%6), resulting in sub(over)-stoichiometry films. Spectroelectrochemical measurements show that the EC effect of NiOx in nonaqueous PC - LiClO4 electrolyte is direct correlation with the nickel vacancy concentration in films, while that in the aqueous KOH solution is nearly uninfluenced upon the change in stoichiometry as P >= %4. The films deposited at P = 6% exhibit higher coloration efficiency of - 25.3 cm(2)C(-1), larger ionic diffusion coefficient of - 2.84 x 10(-14) m(2)s(-1), and broader EC modulation span of 24% in PC - LiClO4 than the other ones. Based upon these values, EC devices featuring a WO3/PMMA - PC - LiClO4/NiOx structure and excellent performances were fabricated. We demonstrated that the nickel anodization should be responsible for the initial "activation" phenomena, which decreases(increases) the number of oxygen(nickel) vacancies. Moreover, the cause of degradation resulting from Li+-ion trapping in the IS layer was also clarified. This work provides a general framework for studying and designing superior EC devices, experimentally as well as theoretically.
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10. |
- Huang, Jing, et al.
(författare)
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Gas exchange in fruits related to skin condition and fruit ripening studied with diode laser spectroscopy
- 2016
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Ingår i: Journal of Biomedical Optics. - 1083-3668. ; 21:12
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Tidskriftsartikel (refereegranskat)abstract
- The concentration of the biologically active molecular oxygen gas is of crucial importance for fruits in the metabolic respiration, maturation, and ripening processes. In our study, oxygen content and oxygen transport in fruits, exemplified by apples and guavas, were studied noninvasively by gas in scattering media absorption spectroscopy. The technique is based on the fact that free gases typically have 10,000 times narrower absorption features than the bulk material. The technique was demonstrated in studies of the influence of the fruit skin in regulating the internal oxygen balance, by observing the signal response of the internal oxygen gas to a transient change in the ambient gas concentration on peeled and unpeeled fruits. In addition, the gas exchange rate at different ripening stages was also studied in intact guavas.
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11. |
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12. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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13. |
- Kraja, Aldi T., et al.
(författare)
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New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals
- 2017
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
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14. |
- Li, Kai, et al.
(författare)
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Metal thermopile infrared detector with vertical graphene
- 2023
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Ingår i: Wuli Xuebao/Acta Physica Sinica. - : Acta Physica Sinica, Chinese Physical Society and Institute of Physics, Chinese Academy of Sciences. - 1000-3290. ; 72:3
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Tidskriftsartikel (refereegranskat)abstract
- Thermopile infrared detector is a kind of detector device mainly composed of thermocouple as the basic unit. Because of its simple principle, no need of cooling equipment, and other advantages, it has been widely used in various fields of production and life. However, the absorption rates of the materials in conventional thermopile devices are poor, and the majority of them are incompatible with microfabrication methods. In this work, a metal thermopile infrared detector with vertical graphene (VG) is designed and fabricated. The VG is grown via plasma enhanced chemical vapor deposition, and retained at the device’s thermal ends to provide the thermopile IR detector’s wideband and high response characteristics. The detector achieves a room temperature responsivity reaching a value as high as 1.53 V/W at 792 nm, which can increase the response results about 28 times and reduce the response time to 0.8 ms compared with the thermopile detector without VG. After systematically measuring the response results, it is finally found that there are three main mechanisms responsible for the response on the composite device. The first one is the response generated by the metal thermopile itself alone. The second one is the response increased eventually by the contribution of VG covered at the metal thermal junction that expands the temperature difference. The last one is the response generated by the temperature gradient existing inside the VG on the surface of the device after the absorption of heat. The portion of each partial response mechanism in the total response is also analyzed, providing a new reference direction for analyzing the response generation mechanism of thermopile detectors with other absorbing materials. The process is compatible with the microfabrication, while the device performance is enhanced and suitable for mass production. Furthermore, by utilizing the surface plasmon resonance to combine VG with metal nanoparticles, the material’ s light absorption is found to be enhanced significantly under the same conditions, and the resulting thermal voltage can be increased to 6 times. The results indicate that VG promises to possess practical applications, in many fields such as photoelectric sensing and power production devices. This technology provides a new method to manufacture high-performance thermopile infrared detectors and other sensor devices.
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15. |
- Mei, Xueshuang, et al.
(författare)
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Human inner ear blood supply revisited : the Uppsala collection of temporal bone - an international resource of education and collaboration
- 2018
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Ingår i: Upsala Journal of Medical Sciences. - : TAYLOR & FRANCIS LTD. - 0300-9734 .- 2000-1967. ; 123:3, s. 131-142
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Uppsala collection of human temporal bones and molds is a unique resource for education and international research collaboration. Micro-computerized tomography (micro-CT) and synchrotron imaging are used to investigate the complex anatomy of the inner ear. Impaired microcirculation is etiologically linked to various inner ear disorders, and recent developments in inner ear surgery promote examination of the vascular system. Here, for the first time, we present three-dimensional (3D) data from investigations of the major vascular pathways and corresponding bone channels.Methods: We used the archival Uppsala collection of temporal bones and molds consisting of 324 inner ear casts and 113 macerated temporal bones. Micro-CT was used to investigate vascular bone channels, and 26 fresh human temporal bones underwent synchrotron radiation phase contrast imaging (SR-PCI). Data were processed by volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and soft tissue analyses.Results: Micro-CT with 3D rendering was superior in reproducing the anatomy of the vascular bone channels, while SR-PCI replicated soft tissues. Arterial bone channels were traced from scala vestibuli (SV) arterioles to the fundus, cochlea, and vestibular apparatus. Drainage routes along the aqueducts were examined.Conclusion: Human inner ear vessels are difficult to study due to the adjoining hard bone. Micro-CT and SR-PCI with 3D reconstructions revealed large portions of the micro-vascular system in un-decalcified specimens. The results increase our understanding of the organization of the vascular system in humans and how altered microcirculation may relate to inner ear disorders. The findings may also have surgical implications.
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16. |
- Mei, Xueshuang, et al.
(författare)
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Three-dimensional imaging of the human internal acoustic canal and arachnoid cistern : a synchrotron study with clinical implications
- 2019
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Ingår i: Journal of Anatomy. - : WILEY. - 0021-8782 .- 1469-7580. ; 234:3, s. 316-326
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Tidskriftsartikel (refereegranskat)abstract
- A thorough knowledge of the gross and micro-anatomy of the human internal acoustic canal (IAC) is essential in vestibular schwannoma removal, cochlear implantation (CI) surgery, vestibular nerve section, and decompression procedures. Here, we analyzed the acoustic-facial cistern of the human IAC, including nerves and anastomoses using synchrotron phase contrast imaging (SR-PCI). A total of 26 fresh human temporal bones underwent SR-PCI. Data were processed using volume-rendering software to create three-dimensional (3D) reconstructions allowing soft tissue analyses, orthogonal sectioning, and cropping. A scalar opacity mapping tool was used to enhance tissue surface borders, and anatomical structures were color-labeled for improved 3D comprehension of the soft tissues. SR-PCI reproduced, for the first time, the variable 3D anatomy of the human IAC, including cranial nerve complexes, anastomoses, and arachnoid membrane invagination (acoustic-facial cistern; an extension of the cerebellopontine cistern) in unprocessed, un-decalcified specimens. An unrecognized system of arachnoid pillars and trabeculae was found to extend between the arachnoid and cranial nerves. We confirmed earlier findings that intra-meatal vestibular schwannoma may grow unseparated from adjacent nerves without duplication of the arachnoid layers. The arachnoid pillars may support and stabilize cranial nerves in the IAC and could also play a role in local fluid hydrodynamics.
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17. |
- Mei, Xueshuang, et al.
(författare)
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Vascular Supply of the Human Spiral Ganglion : Novel Three-Dimensional Analysis Using Synchrotron Phase-Contrast Imaging and Histology
- 2020
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Human spiral ganglion (HSG) cell bodies located in the bony cochlea depend on a rich vascular supply to maintain excitability. These neurons are targeted by cochlear implantation (CI) to treat deafness, and their viability is critical to ensure successful clinical outcomes. The blood supply of the HSG is difficult to study due to its helical structure and encasement in hard bone. The objective of this study was to present the first three-dimensional (3D) reconstruction and analysis of the HSG blood supply using synchrotron radiation phase-contrast imaging (SR-PCI) in combination with histological analyses of archival human cochlear sections. Twenty-six human temporal bones underwent SR-PCI. Data were processed using volume-rendering software, and a representative three-dimensional (3D) model was created to allow visualization of the vascular anatomy. Histologic analysis was used to verify the segmentations. Results revealed that the HSG is supplied by radial vascular twigs which are separate from the rest of the inner ear and encased in bone. Unlike with most organs, the arteries and veins in the human cochlea do not follow the same conduits. There is a dual venous outflow and a modiolar arterial supply. This organization may explain why the HSG may endure even in cases of advanced cochlear pathology.
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18. |
- Ntalla, Ioanna, et al.
(författare)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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19. |
- Peloso, Gina M., et al.
(författare)
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Association of Exome Sequences with Cardiovascular Traits among Blacks in the Jackson Heart Study
- 2016
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 9:4, s. 368-374
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Tidskriftsartikel (refereegranskat)abstract
- Background-The correlation of null alleles with human phenotypes can provide insight into gene function in humans. In individuals of African ancestry, we set out to identify null and damaging missense variants, and test these variants for association with a range of cardiovascular phenotypes. Methods and Results-We performed whole-exome sequencing in 3223 black individuals from the Jackson Heart Study and found a total of 729 666 variant sites with minor allele frequency <5%, including 17 263 null variants and 49 929 missense variants predicted to be damaging by in silico algorithms. We tested null and damaging missense variants within each gene for association with 36 cardiovascular traits. We found 3 associations that met our prespecified level of significance (α=1.1×10-7). Null and damaging missense variants in PCSK9 were associated with 36 mg/dL lower low-density lipoprotein cholesterol (P=3×10-21). Three individuals in their 50s with complete PCSK9 deficiency (each compound heterozygote for PCSK9 p.Y142X and p.C679X) were identified, with one having a coronary artery calcification score in the 83rd percentile despite a low-density lipoprotein cholesterol of 32 mg/dL. A damaging missense variant in HBQ1 (p.G52A) was associated with a 2 pg/cell lower mean corpuscular hemoglobin (P=9×10-13) and rare damaging missense variants in VPS13A with higher red blood cell distribution width (P=9.9×10-8). Conclusions-A limited number of null/damaging alleles with a large effect on cardiovascular traits were detectable in ≈3000 black individuals.
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20. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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21. |
- Tang, Peng Hao, et al.
(författare)
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A patterning technology of transfer-free graphene for transparent electrodes of near-ultraviolet light-emitting diodes
- 2024
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Ingår i: Journal of Materials Chemistry C. - 2050-7534 .- 2050-7526. ; 12:26, s. 9824-9833
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Tidskriftsartikel (refereegranskat)abstract
- Graphene is well known for its excellent physical and chemical properties and can be used in various fields. Its application technology has become an important direction of research. In this study, a patterning technology of transfer-free graphene is reported, and graphene transparent electrodes of near-ultraviolet light-emitting diodes (LEDs) are fabricated accordingly. In the scheme, Ni film plays the dual role of an etching mask and graphene growth catalyst, realizing the patterning growth of graphene. An SiO2 isolation layer is deposited between Ni and the substrate, avoiding the fusing of the substrate with Ni by the high temperature of graphene growth, which makes the method applicable to nominally any high temperature-compatible metal and semiconductor substrates. Both Ni and SiO2 are then removed, thus directly achieving a good contact between graphene and the substrate. The graphene transparent electrodes fabricated by this method greatly improves the performance of near-ultraviolet LEDs, which is even better than that of indium tin oxide (ITO) in the near-ultraviolet band based on the optical measurement results. This scheme avoids any possible damage and contamination of graphene in traditional transfer and lithography patterning processes, which is scalable and suitable for real applications.
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22. |
- Tang, Wanru, et al.
(författare)
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Drought variations in the southeastern Tibetan Plateau region since 1704 and their link to the Atlantic Multidecadal Oscillation
- 2023
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Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - 0031-0182. ; 630
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the long-term history of drought in the Tibetan Plateau region is important to improve understanding of drought frequency in response to future global warming. Although the Tibetan Plateau has become generally wetter recently, the southeastern part of the Tibetan Plateau has become drier since the 2000s. To place this drying trend in a historical context, we conducted tree-ring studies for Abies spectabilis and Tsuga dumosa at three sites in the southeastern Tibetan Plateau, and developed tree-ring width (TRW), earlywood width (EWW), and latewood width (LWW) chronologies to permit local drought reconstruction. Based on correlation between these tree-ring parameters and instrumental meteorological data, the EWW chronologies were identified as suitable variables for reconstructing the average April–July self-calibrating Palmer Drought Index (scPDSI). The reconstruction accounted for 45.86% of the variance in the instrumental record and allowed us to extend the drought record back to 1704 CE. Based on this new dataset, the driest interval was from 1907 to 1919 CE during which time agricultural production fell by about 70% according to written historical records, leading to severe famine. Our findings suggest that this early twentieth century drought was in phase with the previously known drought over the northern Daxing'an Mountains. However, the southeastern Tibetan Plateau drought occurred one decade earlier than the known widespread drought event in North China during the 1920s–1930s. We show that this spatial drought pattern may have been modulated by the Atlantic Multidecadal Oscillation.
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23. |
- Wang, Siqi, et al.
(författare)
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Adjusting Competitive Reaction to Control Nucleation and Growth of MnO2 for a High-Stress Output Electrochemical Actuator
- 2023
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Ingår i: ACS APPLIED ELECTRONIC MATERIALS. - : AMER CHEMICAL SOC. - 2637-6113. ; 5:9, s. 4836-4845
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Tidskriftsartikel (refereegranskat)abstract
- Manganese dioxide (MnO2) with biocompatibility has promising applications in low-voltage electrochemical actuators of implantable medical devices, which can convert electrical energy to mechanical motion. However, the unsatisfactory actuation strain restricts the generation of a larger output stress of MnO2 for practical application. Herein, a competitive reaction-driven-MnO2 (CRD-MnO2) nanorod network was fabricated on a nickel (Ni) thin-film substrate by adjusting the component molar ratios. We find that the competitive reaction between 3,4-ethylene-dioxythiophene (EDOT) polymerization and oxidation of Mn2+ controls the nucleation and growth behavior of MnO2. The variation in the electron environment, newly generated oxygen vacancies, and a higher content of structural water effectively improve the electroactivity of MnO2 and simultaneously cause more serious Jahn-Teller (JT) distortion of the crystal octahedrons. Thus, an excellent output performance simultaneously having a much higher actuating strain of 8.3% and an actuation stress of 390.1 MPa is generated during a redox reaction between Mn4+ and Mn3+ under 0-1 V. Moreover, the CRD-MnO2/Ni composite actuating films assembled on a 3D-printed resin model of a human hand with separated finger joints can perform smooth grasping and releasing actions, demonstrating a huge potential for in vitro rehabilitation exercises and implantability for people with finger dyskinesia. This work provides a strategy for actuator material fabrication by controlling a nucleation and growth process by adjusting a competitive reaction.
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24. |
- Yang, Mei Jie, et al.
(författare)
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Expression and activity of critical digestive enzymes during early larval development of the veined rapa whelk, Rapana venosa (Valenciennes, 1846)
- 2020
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Ingår i: Aquaculture. - : Elsevier BV. - 0044-8486. ; 519
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Tidskriftsartikel (refereegranskat)abstract
- Metamorphosis is a vital developmental event in the life cycle of molluscs and involves extensive morphological and physiological changes. Remodeling of the digestive system is suggested to occur anticipatorily to enable the larva to shift its diet (from filter feeding on microalgae to feeding on small bivalves) after metamorphosis. Changes in the profiles and activities of digestive enzymes, the main executors of digestion, can reflect substantial remodeling of the digestive system. Artificial aquaculture of Rapana venosa, an important commercial shellfish in China, has been hampered because the transition of its food habit during metamorphosis makes determining the timing and dose for bait regulation difficult. In the present study, full-length cDNA sequences encoding cellulase and trypsin were characterized, and cellulase and trypsin mRNA expression levels were analyzed. Additionally, patterns in the activities of six digestive enzymes, including trypsin and cellulase, were investigated throughout the early developmental stage of R. venosa. In the present study, the full-length cDNA of the cellulase gene, comprising 2,086 bp, was found to contain a 1,719-bp open reading frame encoding 572 amino acids, and the full-length cDNA of the trypsin gene was found to be 1,587 bp in length and contained an 855-bp open reading frame encoding 284 amino acids. Quantitative real-time PCR showed that the cellulase levels in R. venosa increased beginning at the early intramembrane veliger stage, whereas cellulase activity was significantly increased in the one-spiral whorl stage. The mRNA expression and activity of trypsin were greatly increased in the juvenile stage (postlarva), whereas those of cellulase were decreased during this stage, which indicated functional changes in the digestive system during larval food habit transition. Our results showed that remodeling of the digestive system occurs prior to metamorphosis and suggest that animal bait should be provided as early as possible to R. venosa in the four-spiral whorl stage to meet its nutritional requirements for the development of its digestive system and to ensure successful metamorphosis of competent larvae.
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25. |
- Young, William J., et al.
(författare)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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