1. |
|
|
2. |
|
|
3. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)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.
|
|
4. |
- Sampson, Joshua N., et al.
(författare)
-
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
-
Tidskriftsartikel (refereegranskat)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.
|
|
5. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
6. |
- Chen, I-Hua, et al.
(författare)
-
Psychometric properties of the Depression, Anxiety, and Stress Scale (DASS-21) among different Chinese populations : A cross-sectional and longitudinal analysis
- 2023
-
Ingår i: Acta Psychologica. - : Elsevier. - 0001-6918 .- 1873-6297. ; 240
-
Tidskriftsartikel (refereegranskat)abstract
- Given that there is limited evidence concerning the psychometric properties of DASS-21 when applied to primary school students, the present study undertook a comprehensive exploration of the psychometric evidence supporting the use of the DASS-21 within this demographic. The research comprised three studies. In Study 1, the basic psychometric properties of internal consistency and construct validity were examined. A total of 3138 primary school students from three provinces in mainland China participated. The internal reliability of the overall scale was 0.93, and for all the subscales, it was higher than 0.80. Construct validity was partially supported. Both exploratory and confirmatory factor analyses upheld the factorial validity of the original three-factor structure. While convergent validity was established, the results showed unsatisfactory discriminant validity. The bifactor model showed that DASS-21 raw scores predominantly indicated the general factor, evidenced by the high explained common variance and omega-hierarchical values. However, the contributions from the three specific factors were minimal, with their omega hierarchical values all below 0.15. In Study 2, a longitudinal design was adopted, tracking 1366 primary school students from Southwest China over a three-month interval. The results further confirmed that the DASS-21 exhibited scalar time-invariance. The latent mean analysis showed that there were no statistically significant differences in the latent means of depression, anxiety, and stress between Time 1 and Time 2. In Study 3, which included 364 college students and 483 enterprise workers, the results demonstrated that the DASS-21 had measurement invariance across different populations. The latent mean analysis further confirmed that, in terms of the latent mean of all three subscales, both college students and enterprise workers had significantly higher scores than primary school students. Overall, the findings indicated that the DASS-21 is a suitable tool for screening schoolchildren for general psychological distress, but it is not suitable for discerning distinct negative mood state disorders.
|
|
7. |
- Kato, Norihiro, et al.
(författare)
-
Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
-
Tidskriftsartikel (refereegranskat)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.
|
|
8. |
- Kärkäs, Markus D., et al.
(författare)
-
Metal-Ligand Cooperation in Single-Site Ruthenium Water Oxidation Catalysts : A Combined Experimental and Quantum Chemical Approach
- 2018
-
Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 57:17, s. 10881-10895
-
Tidskriftsartikel (refereegranskat)abstract
- Catalysts for oxidation of water to molecular oxygen are essential in solar-driven water splitting. In order to develop more efficient catalysts for this oxidatively demanding reaction, it is vital to have mechanistic insight in order to understand how the catalysts operate. Herein, we report the mechanistic details associated with the two Ru catalysts 1 and 2. Insight into the mechanistic landscape of water oxidation catalyzed by the two single-site Ru catalysts was revealed by the use of a combination of experimental techniques and quantum chemical calculations. On the basis of the obtained results, detailed mechanisms for oxidation of water by complexes 1 and 2 are proposed. Although the two complexes are structurally related, two deviating mechanistic scenarios are proposed with metal-ligand cooperation being an important feature in both processes. The proposed mechanistic platforms provide insight for the activation of water or related small molecules through nontraditional and previously unexplored routes.
|
|
9. |
- Li, Ying-Ying, et al.
(författare)
-
Mechanism of Water Oxidation Catalyzed by a Mononuclear Manganese Complex
- 2017
-
Ingår i: ChemSusChem. - : Wiley. - 1864-5631 .- 1864-564X. ; 10:5, s. 903-911
-
Tidskriftsartikel (refereegranskat)abstract
- The design and synthesis of biomimetic Mn complexes to catalyze oxygen evolution is a very appealing goal because water oxidation in nature employs a Mn complex. Recently, the mononuclear Mn complex [LMnII(H2O)(2)](2+) [1, L=Py2N(tBu)(2), Py= pyridyl] was reported to catalyze water oxidation electro-chemically at an applied potential of 1.23 V at pH 12.2 in aqueous solution. Density functional calculations were performed to elucidate the mechanism of water oxidation promoted by this catalyst. The calculations showed that 1 can lose two protons and one electron readily to produce [LMnIII(OH)(2)](+) (2), which then undergoes two sequential proton-coupled electron-transfer processes to afford [(LMnOO)-O-V](+) (4). The O-O bond formation can occur through direct coupling of the two oxido ligands or through nucleophilic attack of water. These two mechanisms have similar barriers of approximately 17 kcal mol(-1). The further oxidation of 4 to generate [(LMnO)-O-VI-O](2+) (5), which enables O-O bond formation, has a much higher barrier. In addition, ligand degradation by C-H activation has a similar barrier to that for the O-O bond formation, and this explains the relatively low turnover number of this catalyst.
|
|
10. |
- Li, Ying-Ying, et al.
(författare)
-
Quantum Chemical Study of the Mechanism of Water Oxidation Catalyzed by a Heterotrinuclear Ru2Mn Complex
- 2019
-
Ingår i: ChemSusChem. - : Wiley. - 1864-5631 .- 1864-564X. ; 12:5, s. 1101-1110
-
Tidskriftsartikel (refereegranskat)abstract
- The heterotrinuclear complex A {[Ru-II(H2O)(tpy)](2)(mu-[Mn-II(H2O)(2)(bpp)(2)])}(4+) [tpy=2,2 ':6 ',2 ''-terpyridine, bpp=3,5-bis(2-pyridyl)pyrazolate] was found to catalyze water oxidation both electrochemically and photochemically with [Ru(bpy)(3)](3+) (bpy=2,2 '-bipyridine) as the photosensitizer and Na2S2O8 as the electron acceptor in neutral phosphate buffer. The mechanism of water oxidation catalyzed by this unprecedented trinuclear complex was studied by density functional calculations. The calculations showed that a series of oxidation and deprotonation events take place from A, leading to the formation of complex 1 (formal oxidation state of Ru1(IV)Mn(III)Ru2(III)), which is the starting species for the catalytic cycle. Three sequential oxidations of 1 result in the generation of the catalytically competing species 4 (formal oxidation state of Ru1(IV)Mn(V)Ru2(IV)), which triggers the O-O bond formation. The direct coupling of two adjacent oxo ligands bound to Ru and Mn leads to the production of a superoxide intermediate Int1. This step was calculated to have a barrier of 7.2 kcal mol(-1) at the B3LYP*-D3 level. Subsequent O-2 release from Int1 turns out to be quite facile. Other possible pathways were found to be much less favorable, including water nucleophilic attack, the coupling of an oxo and a hydroxide, and the direct coupling pathway at a lower oxidation state ((RuMnRuIV)-Mn-IV-Ru-IV).
|
|
11. |
- Wang, Zhaoming, et al.
(författare)
-
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
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
-
Tidskriftsartikel (refereegranskat)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.
|
|
12. |
- Chen, I-Hua, et al.
(författare)
-
Evaluating a cross-lagged panel model between problematic internet use and psychological distress and cross-level mediation of school administrator support on problematic internet use : The serial mediating role of psychological needs thwarting of online teaching and psychological distress
- 2022
-
Ingår i: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundTo reduce the transmission of COVID-19, many teachers across the globe, including teachers in China, were required to teach online. This shift to online teaching can easily result in psychological need thwarting (PNT) of teachers' psychological basic needs (autonomy, competence, and relatedness), leaving them vulnerable to negative psychological outcomes. Resulting negative emotional state may lead to problematic internet use (PIU), which can lead to further psychological distress, forming a vicious cycle. MethodsThe present study was conducted using a cross-lagged panel model (with longitudinal data) and hierarchical linear modeling (HLM) (with cross-sectional data). The aims were to investigate (i) the reciprocal relationships between two specific forms of PIU [problematic social media use (PSMU) and problematic gaming (PG)] and psychological distress among schoolteachers, and (ii) the influence of administrators' support on schoolteachers' PIU through a cross-level serial mediation model (PNT of online teaching was the first mediator and psychological distress was the second mediator affected by PNT of online teaching). Primary and secondary schoolteachers (N = 980; mean age = 34.76; 82.90% females) participated in two surveys (Time 1: mid-November 2021; Time 2: early-January 2022). ResultsResults indicated that (i) high psychological distress at Time 1 was associated with increased levels of PSMU and PG at Time 2. Inversely, PG at Time 1 was associated with increased psychological distress at Time 2, although PSMU at Time 1 did not have a significant influence on psychological distress at Time 2; (ii) during Time 1, increased administrative support contributed to alleviating teachers' psychological needs thwarting of online teaching, thereby lowering their psychological distress which, in turn, resulted in a decrease in PG. ConclusionPG had a stronger negative influence on teachers' psychological distress than PSMU. To relieve teachers' PG, administrative support can alleviate teachers' psychological needs thwarting of online teaching and psychological distress. Based on this finding, school managers must consider effective ways to support teachers during mandatory online teaching.
|
|
13. |
- Lai, Ian-Lin, et al.
(författare)
-
Gas outflow and dust transport of comet 67P/Churyumov-Gerasimenko
- 2016
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 462, s. S533-S546
-
Tidskriftsartikel (refereegranskat)abstract
- Because of the diurnal thermal cycle and the irregular shape of the nucleus, gas outflow of comet 67P/Churyumov-Gerasimenko could be highly anisotropic as indicated by the colliminated dust jet structures on the sunlit side. Based on the OSIRIS imaging observations of the outgassing effect, a simple model of surface sublimation can be constructed by taking into account the dependence on the solar insolation. With preliminary information on the time variability of the global gas production rate, a sequence of gas coma models can be generated at different epochs before and after perihelion. We also investigate different patterns of dust particle dynamics under the influences of nuclear rotation and gas drag. From these considerations, a consistent picture of the spatial distribution of dusty materials across the surface of comet 67P as it moves around the perihelion can be developed. It is found that because of the redeposition of the ejected dust from the Southern hemisphere to the Northern hemisphere during the southern summer season the Hapi region could gain up to 0.4 m while the Wosret region would lose up to 1.8 m of dust mantle per orbit.
|
|
14. |
|
|
15. |
- Liao, Qingbi, et al.
(författare)
-
Channel Capacity Analysis of Different Mobile Antenna Array Topologies in the Outdoor Urban Environment for 5G mm Wave System
- 2017
-
Ingår i: 2017 IEEE Antennas and Propagation Society International Symposium, Proceedings. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538632840 ; , s. 1473-1474
-
Konferensbidrag (refereegranskat)abstract
- The 15 and 28 GHz frequency bands have been identified as interesting candidates for future 5G cellular communication systems. In this paper, based on ray-tracing simulations, we investigate the channel capacities at 15 and 28 GHz for a number of different array processing techniques, including beamforming, spatial multiplexing, and two types of hybrid beamforming. This is done for an 8 x 32 multiple input multiple output system, for the single user case. The hybrid beamforming techniques combines the beamforming and spatial multiplexing techniques, in order to reduce the number of analog-to-digital converters and thereby reducing the system complexity, while still maintaining multiplexing capabilities for improved system capacities. The achieved channel capacities the hybrid beamforming techniques with up to four parallel streams outperforms pure beamforming, but does not reach capacities close to that of full spatial multiplexing. This indicates that the outdoor channel can support multiplexing of more than four parallel data streams to a single user.
|
|
16. |
- Liao, Qingbi, et al.
(författare)
-
Simulations and Measurements of 15 and 28 GHz Indoor Channels with Different Array Configurations
- 2017
-
Ingår i: 2017 INTERNATIONAL WORKSHOP ON ANTENNA TECHNOLOGY. - : IEEE. - 9781509051779 ; , s. 256-259
-
Konferensbidrag (refereegranskat)abstract
- There are many different frequency bands above 6 GHz and into the mm-wave range above 30 GHz that are possible candidates for use in future 5G cellular systems. In this paper, we present some results for wireless channels at 15 and 28 GHz in an indoor scenario. The results are based on both measurements and ray tracing simulations. Basic comparisons of measured and simulated power-delay profiles, angle of departure and received power are presented to give an insight to the possibilities and limitations of utilizing ray tracing to characterize the indoor wireless channel at 15 and 28 GHz. We show that it is important to consider human body shadowing as well as finer structures and details in the ray tracing environment model in order to achieve reasonable results. Lastly, we also perform ray tracing simulations to assess the performance of a number of different array signal processing techniques, including beamforming, hybrid beamforming and spatial multiplexing.
|
|
17. |
- Liao, Yufeng, et al.
(författare)
-
A facile way to fabricate CdSe quantum dots coated with silica and the fluorescence property
- 2006
-
Ingår i: Proceedings of International Symposium on Biophotonics, Nanophotonics and Metamaterials. - 9780780397736 ; , s. 342-345
-
Konferensbidrag (refereegranskat)abstract
- Good quality quantum dots (QDs) CdSe were prepared with a novel and non-TOP method. Quantum dots with different sizes ranging from 2 to 5 rim could be obtained by removing aliquots of reaction solution at different time intervals. The quantum dots CdSe (core) -silica (shell) was fabricated by a rnicroemulsion method. Transmission electron microscopy (TEM) images confirmed the well monodispersed QDs and the silica shell around CdSe core respectively. UV-Vis absorption and photoluminescence spectra clearly indicated that both the original QDs and the silica-coated QDs had good fluorescence properties. The quantum dots coated with silica shell are water-soluble and less toxic (due to the silica shell), which are anticipated as fluorescent probes for biosensing and imaging applications such as tumor detection of pre-cancers.
|
|
18. |
- Luo, Yiqi, et al.
(författare)
-
Matrix Approach to Land Carbon Cycle Modeling
- 2022
-
Ingår i: Journal of Advances in Modeling Earth Systems. - 1942-2466. ; 14:7
-
Forskningsöversikt (refereegranskat)abstract
- Land ecosystems contribute to climate change mitigation by taking up approximately 30% of anthropogenically emitted carbon. However, estimates of the amount and distribution of carbon uptake across the world's ecosystems or biomes display great uncertainty. The latter hinders a full understanding of the mechanisms and drivers of land carbon uptake, and predictions of the future fate of the land carbon sink. The latter is needed as evidence to inform climate mitigation strategies such as afforestation schemes. To advance land carbon cycle modeling, we have developed a matrix approach. Land carbon cycle models use carbon balance equations to represent carbon exchanges among pools. Our approach organizes this set of equations into a single matrix equation without altering any processes of the original model. The matrix equation enables the development of a theoretical framework for understanding the general, transient behavior of the land carbon cycle. While carbon input and residence time are used to quantify carbon storage capacity at steady state, a third quantity, carbon storage potential, integrates fluxes with time to define dynamic disequilibrium of the carbon cycle under global change. The matrix approach can help address critical contemporary issues in modeling, including pinpointing sources of model uncertainty and accelerating spin-up of land carbon cycle models by tens of times. The accelerated spin-up liberates models from the computational burden that hinders comprehensive parameter sensitivity analysis and assimilation of observational data to improve model accuracy. Such computational efficiency offered by the matrix approach enables substantial improvement of model predictions using ever-increasing data availability. Overall, the matrix approach offers a step change forward for understanding and modeling the land carbon cycle.
|
|
19. |
- Längin, Matthias, et al.
(författare)
-
Cold non-ischemic heart preservation with continuous perfusion prevents early graft failure in orthotopic pig-to-baboon xenotransplantation
- 2021
-
Ingår i: Xenotransplantation. - : Wiley. - 0908-665X .- 1399-3089. ; 28:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Successful preclinical transplantations of porcine hearts into baboon recipients are required before commencing clinical trials. Despite years of research, over half of the orthotopic cardiac xenografts were lost during the first 48 hours after transplantation, primarily caused by perioperative cardiac xenograft dysfunction (PCXD). To decrease the rate of PCXD, we adopted a preservation technique of cold non-ischemic perfusion for our ongoing pig-to-baboon cardiac xenotransplantation project. Methods: Fourteen orthotopic cardiac xenotransplantation experiments were carried out with genetically modified juvenile pigs (GGTA1- KO/hCD46/hTBM) as donors and captive-bred baboons as recipients. Organ preservation was compared according to the two techniques applied: cold static ischemic cardioplegia (IC; n = 5) and cold non-ischemic continuous perfusion (CP; n = 9) with an oxygenated albumin-containing hyperoncotic cardioplegic solution containing nutrients, erythrocytes and hormones. Prior to surgery, we measured serum levels of preformed anti-non-Gal-antibodies. During surgery, hemodynamic parameters were monitored with transpulmonary thermodilution. Central venous blood gas analyses were taken at regular intervals to estimate oxygen extraction, as well as lactate production. After surgery, we measured troponine T and serum parameters of the recipient’s kidney, liver and coagulation functions. Results: In porcine grafts preserved with IC, we found significantly depressed systolic cardiac function after transplantation which did not recover despite increasing inotropic support. Postoperative oxygen extraction and lactate production were significantly increased. Troponin T, creatinine, aspartate aminotransferase levels were pathologically high, whereas prothrombin ratios were abnormally low. In three of five IC experiments, PCXD developed within 24 hours. By contrast, all nine hearts preserved with CP retained fully preserved systolic function, none showed any signs of PCXD. Oxygen extraction was within normal ranges; serum lactate as well as parameters of organ functions were only mildly elevated. Preformed anti-non-Gal-antibodies were similar in recipients receiving grafts from either IC or CP preservation. Conclusions: While standard ischemic cardioplegia solutions have been used with great success in human allotransplantation over many years, our data indicate that they are insufficient for preservation of porcine hearts transplanted into baboons: Ischemic storage caused severe impairment of cardiac function and decreased tissue oxygen supply, leading to multi-organ failure in more than half of the xenotransplantation experiments. In contrast, cold non-ischemic heart preservation with continuous perfusion reliably prevented early graft failure. Consistent survival in the perioperative phase is a prerequisite for preclinical long-term results after cardiac xenotransplantation.
|
|
20. |
- Längin, Matthias, et al.
(författare)
-
Consistent success in life-supporting porcine cardiac xenotransplantation
- 2018
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 564:7736, s. 430-433
-
Tidskriftsartikel (refereegranskat)abstract
- Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need1–3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative4. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons5. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once6. Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation7.
|
|
21. |
- Petimar, Joshua, et al.
(författare)
-
A Pooled Analysis of 15 Prospective Cohort Studies on the Association between Fruit, Vegetable, and Mature Bean Consumption and Risk of Prostate Cancer.
- 2017
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 26:8, s. 1276-1287
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Relationships between fruit, vegetable, and mature bean consumption and prostate cancer risk are unclear.Methods: We examined associations between fruit and vegetable groups, specific fruits and vegetables, and mature bean consumption and prostate cancer risk overall, by stage and grade, and for prostate cancer mortality in a pooled analysis of 15 prospective cohorts, including 52,680 total cases and 3,205 prostate cancer-related deaths among 842,149 men. Diet was measured by a food frequency questionnaire or similar instrument at baseline. We calculated study-specific relative risks using Cox proportional hazards regression, and then pooled these estimates using a random effects model.Results: We did not observe any statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group (including total fruits and vegetables, total fruits, total vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato products), nor specific fruit and vegetables. In addition, we observed few statistically significant results for other prostate cancer outcomes. Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09. There was no evidence of effect modification for any association by age or body mass index.Conclusions: Results from this large, international, pooled analysis do not support a strong role of collective groupings of fruits, vegetables, or mature beans in prostate cancer.Impact: Further investigation of other dietary exposures, especially indicators of bioavailable nutrient intake or specific phytochemicals, should be considered for prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(8); 1276-87. ©2017 AACR.
|
|
22. |
- Robbins, Hilary A., et al.
(författare)
-
Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program
- 2023
-
Ingår i: Annals of Epidemiology. - : Elsevier. - 1047-2797 .- 1873-2585. ; 77, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize low-dose CT (LDCT) lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL. The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1161 proteins in a nested-case control study within 2 prospective cohorts (n = 252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n = 479 cases and 479 controls). Eligible participants had a current or former history of smoking and cases were diagnosed up to 3 years following blood draw. The Nodule Malignancy project measured 1078 proteins among participants with a heavy smoking history within four LDCT screening studies (n = 425 cases diagnosed up to 5 years following blood draw, 430 benign-nodule controls, and 398 nodule-free controls). The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n = 1696 cases and 2926 subcohort representatives), and in the Nodule Malignancy project within five LDCT screening studies (n = 675 cases, 680 benign-nodule controls, and 648 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.
|
|
23. |
- Santangelo, James S., et al.
(författare)
-
Global urban environmental change drives adaptation in white clover
- 2022
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
-
Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
|
|
24. |
- Song, Dan-Na, et al.
(författare)
-
Luminescent Thermochromic Silver Iodides as Wavelength-Dependent Thermometers
- 2020
-
Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 59:18, s. 13067-13077
-
Tidskriftsartikel (refereegranskat)abstract
- Luminescent thermochromic materials with a dramatic shift of emission band under different temperatures are highly desirable in temperature sensing fields. However, the design of the synthesis of such compounds remains a great challenge. In this work, two new luminescent thermochromic silver iodides, (emIm)Ag3I4 (1) and (emIm)Ag2I3 (2) (emIm = 1-ethyl-3-methyl imidazole), have been synthesized under solvothermal conditions. Compound 1 features a [Ag3I4]− anionic layer, while compound 2 possesses an infinite [Ag2I3]− chain structure, both of which are charge balanced by emIm+ cations. Particularly, they display luminescent thermochromism with a significant wavelength shift of emission maximum with temperature change. They represent rare examples of infinite layered or chain silver iodides that show luminescent thermochromism. Furthermore, the results indicate that compounds 1 and 2 are promising wavelength-dependent luminescent thermometers.
|
|
25. |
- Sun, Bing, et al.
(författare)
-
Solid polymer electrolyte coating from a bifunctional monomer for three-dimensional microbattery applications
- 2013
-
Ingår i: Journal of Power Sources. - : Elsevier BV. - 0378-7753 .- 1873-2755. ; 238, s. 435-441
-
Tidskriftsartikel (refereegranskat)abstract
- This work comprises the synthesis and characterization of a novel solid polymer electrolyte based on oligomeric polyetheramine substituted with a methacrylic group at one of its three chain ends. This modification introduces a bifunctionality to the PEA monomer it can act both as polymerizable unit and surfactant. Thin and pinhole-free polymer electrolyte layers could be constructed with thicknesses in the order of <1 mu m using UV-initiated polymerization. The electrolyte exhibits good electrochemical and chemical stability up to 4 V vs. Li+/Li. LiFePO4 cathode coated with the electrolyte was cycled against lithium at 60 degrees C, and displayed reasonable capacity values (similar to 140 mAh g(-1)) for 10 cycles, where after Li dendrite formation contributed to battery instabilities.
|
|