| 1. |
|
|
| 2. |
- Markmann, James F., et al.
(författare)
-
Executive Summary of IPITA-TTS Opinion Leaders Report on the Future of beta-Cell Replacement
- 2016
-
Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 100:7, s. E25-E31
-
Forskningsöversikt (refereegranskat)abstract
- The International Pancreas and Islet Transplant Association (IPITA), in conjunction with the Transplantation Society (TTS), convened a workshop to consider the future of pancreas and islet transplantation in the context of potential competing technologies that are under development, including the artificial pancreas, transplantation tolerance, xenotransplantation, encapsulation, stem cell derived beta cells, beta cell proliferation, and endogenous regeneration. Separate workgroups for each topic and then the collective group reviewed the state of the art, hurdles to application, and proposed research agenda for each therapy that would allow widespread application. Herein we present the executive summary of this workshop that focuses on obstacles to application and the research agenda to overcome them; the full length article with detailed background for each topic is published as an online supplement to Transplantation.
|
|
| 3. |
- Raghavan, Maanasa, et al.
(författare)
-
Genomic evidence for the Pleistocene and recent population history of Native Americans
- 2015
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6250
-
Tidskriftsartikel (refereegranskat)abstract
- Howand when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
|
|
| 4. |
- Campistol, Josep M., et al.
(författare)
-
Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation
- 2006
-
Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 17:2, s. 581-589
-
Tidskriftsartikel (refereegranskat)abstract
- Sirolimus (SRL) is a mammalian target of rapamycin inhibitor that, in contrast to cyclosporine (CsA), has been shown to inhibit rather than promote cancers in experimental models. At 3 mo +/- 2 wk after renal transplantation, 430 of 525 enrolled patients were randomly assigned to remain on SRL-CsA-steroids (ST) or to have CsA withdrawn and SRL troughs increased two-fold (SRL-ST). Median times to first skin and nonskin malignancies were compared between treatments using a survival analysis. Mean annualized rates of skin malignancy were calculated, and the relative risk was determined using a Poisson model. Malignancy-free survival rates for nonskin malignancies were compared using Kaplan-Meier estimates and the log-rank test. At 5 yr, the median time to a first skin carcinoma was delayed (491 versus 1126 d; log-rank test, P = 0.007), and the risk for an event was significantly lower with SRL-ST therapy (relative risk SRL-ST to SRL-CsA-ST 0.346; 95% confidence interval 0.227 to 0.526; P < 0.001, intention-to-treat analysis). The relative risks for both basal and squamous cell carcinomas were significantly reduced. Kaplan-Meier estimates of nonskin cancer were 9.6 versus 4.0% (SRL-CsA-ST versus SRL-ST; P = 0.032, intention-to-treat analysis). Nonskin cancers included those of the lung, larynx, oropharynx, kidney, gastrointestinal tract, prostate, breast, thyroid, and cervix as well as glioma, liposarcoma, astrocytoma, leukemia, lymphoma, and Kaposi's sarcoma. Patients who received SRL-based, calcineurin inhibitor-free therapy after CsA withdrawal at month 3 had a reduced incidence of both skin and nonskin malignancies at 5 yr after renal transplantation compared with those who received SRL therapy combined with CsA. Longer follow-up and additional trials are needed to confirm these promising results.
|
|
| 5. |
- Friend, Peter, et al.
(författare)
-
Incidence of anemia in sirolimus-treated renal transplant recipients : the importance of preserving renal function
- 2007
-
Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 20:9, s. 754-760
-
Tidskriftsartikel (refereegranskat)abstract
- Sirolimus (SRL) has a concentration-related effect on hematopoiesis. In this study, 430 renal transplant recipients were randomized (1:1) 3 months post-transplantation to continue SRL-cyclosporine (CsA)-steroids (ST) or to have CsA withdrawn (SRL-ST). Over 5 years, on therapy calculated glomerular filtration rate (GFR), hematological indices, erythropoietin (EPO) use, and rates of mild, moderate, and severe anemia were determined. Longitudinal analyses using linear mixed models examined covariates predicting hemoglobin (Hgb) levels. Mean Hgb was significantly lower with SRL-ST at 6 months; but subsequently became significantly higher (at 2 years, 129 vs. 135 g/l, SRL-CsA-ST vs. SRL-ST, P<0.001). Mean corpuscular volume was low with both therapies, and significantly lower with SRL-ST. EPO use was similar in the two groups, approximately 30% during the first year and 10% thereafter. The incidence of anemia was significantly higher with SRL-CsA-ST>or=2 years. At year 5, only 39.1% of SRL-CsA-ST patients had normal Hgb vs. 68.5% of SRL-ST patients. GFR and recipient age as well as the interaction term x treatment time were significant covariates predicting Hgb. CsA withdrawal followed by SRL immunotherapy resulted in significantly less anemia than SRL-CsA-ST, despite twofold higher SRL exposure. This suggests that the improvement in GFR accompanying CsA withdrawal may mitigate the effect of SRL on hematopoiesis. (ClinicalTrials.gov number: NCT00428064).
|
|
| 6. |
- Gorman, Jeffrey, et al.
(författare)
-
Deoxyribonucleic Acid Encoded and Size-Defined π-Stacking of Perylene Diimides
- 2022
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 144:1, s. 368-376
-
Tidskriftsartikel (refereegranskat)abstract
- Natural photosystems use protein scaffolds to control intermolecular interactions that enable exciton flow, charge generation, and long-range charge separation. In contrast, there is limited structural control in current organic electronic devices such as OLEDs and solar cells. We report here the DNA-encoded assembly of pi-conjugated perylene diimides (PDIs) with deterministic control over the number of electronically coupled molecules. The PDIs are integrated within DNA chains using phosphoramidite coupling chemistry, allowing selection of the DNA sequence to either side, and specification of intermolecular DNA hybridization. In this way, we have developed a "toolbox" for construction of any stacking sequence of these semiconducting molecules. We have discovered that we need to use a full hierarchy of interactions: DNA guides the semiconductors into specified close proximity, hydrophobic-hydrophilic differentiation drives aggregation of the semiconductor moieties, and local geometry and electrostatic interactions define intermolecular positioning. As a result, the PDIs pack to give substantial intermolecular pi wave function overlap, leading to an evolution of singlet excited states from localized excitons in the PDI monomer to excimers with wave functions delocalized over all five PDIs in the pentamer. This is accompanied by a change in the dominant triplet forming mechanism from localized spin-orbit charge transfer mediated intersystem crossing for the monomer toward a delocalized excimer process for the pentamer. Our modular DNA-based assembly reveals real opportunities for the rapid development of bespoke semiconductor architectures with molecule-by-molecule precision.
|
|
| 7. |
- Guo, Renjun, et al.
(författare)
-
Degradation mechanisms of perovskite solar cells under vacuum and one atmosphere of nitrogen
- 2021
-
Ingår i: Nature Energy. - : Springer Nature. - 2058-7546. ; 6:10, s. 977-
-
Tidskriftsartikel (refereegranskat)abstract
- Extensive studies have focused on improving the operational stability of perovskite solar cells, but few have surveyed the fundamental degradation mechanisms. One aspect overlooked in earlier works is the effect of the atmosphere on device performance during operation. Here we investigate the degradation mechanisms of perovskite solar cells operated under vacuum and under a nitrogen atmosphere using synchrotron radiation-based operando grazing-incidence X-ray scattering methods. Unlike the observations described in previous reports, we find that light-induced phase segregation, lattice shrinkage and morphology deformation occur under vacuum. Under nitrogen, only lattice shrinkage appears during the operation of solar cells, resulting in better device stability. The different behaviour under nitrogen is attributed to a larger energy barrier for lattice distortion and phase segregation. Finally, we find that the migration of excessive PbI2 to the interface between the perovskite and the hole transport layer degrades the performance of devices under vacuum or under nitrogen. Understanding degradation mechanisms in perovskite solar cells is key to their development. Now, Guo et al. show a greater degradation of the perovskite structure and morphology for devices operated under vacuum than under nitrogen.
|
|
| 8. |
- Orsborne, Sarah R.E., et al.
(författare)
-
Photogeneration of Spin Quintet Triplet-Triplet Excitations in DNA-Assembled Pentacene Stacks
- 2023
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126. ; 145:9, s. 5431-5438
-
Tidskriftsartikel (refereegranskat)abstract
- Singlet fission (SF), an exciton-doubling process observed in certain molecular semiconductors where two triplet excitons are generated from one singlet exciton, requires correctly tuned intermolecular coupling to allow separation of the two triplets to different molecular units. We explore this using DNA-encoded assembly of SF-capable pentacenes into discrete π-stacked constructs of defined size and geometry. Precise structural control is achieved via a combination of the DNA duplex formation between complementary single-stranded DNA and the local molecular geometry that directs the SF chromophores into a stable and predictable slip-stacked configuration, as confirmed by molecular dynamics (MD) modeling. Transient electron spin resonance spectroscopy revealed that within these DNA-assembled pentacene stacks, SF evolves via a bound triplet pair quintet state, which subsequently converts into free triplets. SF evolution via a long-lived quintet state sets specific requirements on intermolecular coupling, rendering the quintet spectrum and its zero-field-splitting parameters highly sensitive to intermolecular geometry. We have found that the experimental spectra and zero-field-splitting parameters are consistent with a slight systematic strain relative to the MD-optimized geometry. Thus, the transient electron spin resonance analysis is a powerful tool to test and refine the MD-derived structure models. DNA-encoded assembly of coupled semiconductor molecules allows controlled construction of electronically functional structures, but brings with it significant dynamic and polar disorders. Our findings here of efficient SF through quintet states demonstrate that these conditions still allow efficient and controlled semiconductor operation and point toward future opportunities for constructing functional optoelectronic systems.
|
|
| 9. |
- Schewe, Jacob, et al.
(författare)
-
State-of-the-art global models underestimate impacts from climate extremes
- 2019
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Global impact models represent process-level understanding of how natural and human systems may be affected by climate change. Their projections are used in integrated assessments of climate change. Here we test, for the first time, systematically across many important systems, how well such impact models capture the impacts of extreme climate conditions. Using the 2003 European heat wave and drought as a historical analogue for comparable events in the future, we find that a majority of models underestimate the extremeness of impacts in important sectors such as agriculture, terrestrial ecosystems, and heat-related human mortality, while impacts on water resources and hydropower are overestimated in some river basins; and the spread across models is often large. This has important implications for economic assessments of climate change impacts that rely on these models. It also means that societal risks from future extreme events may be greater than previously thought.
|
|
| 10. |
- Wieduwilt, Matthew J., et al.
(författare)
-
Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia
- 2022
-
Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:1, s. 339-357
-
Tidskriftsartikel (refereegranskat)abstract
- The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLAmatched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P <_ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P <_ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (<_18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.
|
|
