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  • 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.
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  • Beyer, J., et al. (författare)
  • Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer
  • 2013
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 24:4, s. 878-888
  • Forskningsöversikt (refereegranskat)abstract
    • In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, similar to 50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.
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  • De Gasperin, F., et al. (författare)
  • M 87 at metre wavelengths: the LOFAR picture
  • 2012
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 547, s. article no. 56-
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. M87 is a giant elliptical galaxy located in the centre of the Virgo cluster, which harbours a supermassive black hole of mass 6.4x10(9) M-circle dot, whose activity is responsible for the extended (80 kpc) radio lobes that surround the galaxy. The energy generated by matter falling onto the central black hole is ejected and transferred to the intra-cluster medium via a relativistic jet and morphologically complex systems of buoyant bubbles, which rise towards the edges of the extended halo. Aims. To place constraints on past activity cycles of the active nucleus, images of M 87 were produced at low radio frequencies never explored before at these high spatial resolution and dynamic range. To disentangle different synchrotron models and place constraints on source magnetic field, age and energetics, we also performed a detailed spectral analysis of M 87 extended radio-halo. Methods. We present the first observations made with the new Low-Frequency Array (LOFAR) of M 87 at frequencies down to 20 MHz. Three observations were conducted, at 15-30 MHz, 30-77 MHz and 116-162 MHz. We used these observations together with archival data to produce a low-frequency spectral index map and to perform a spectral analysis in the wide frequency range 30 MHz-10 GHz. Results. We do not find any sign of new extended emissions; on the contrary the source appears well confined by the high pressure of the intra-cluster medium. A continuous injection of relativistic electrons is the model that best fits our data, and provides a scenario in which the lobes are still supplied by fresh relativistic particles from the active galactic nuclei. We suggest that the discrepancy between the low-frequency radio-spectral slope in the core and in the halo implies a strong adiabatic expansion of the plasma as soon as it leaves the core area. The extended halo has an equipartition magnetic field strength of similar or equal to 10 mu G, which increases to similar or equal to 13 mu G in the zones where the particle flows are more active. The continuous injection model for synchrotron ageing provides an age for the halo of similar or equal to 40 Myr, which in turn provides a jet kinetic power of 6-10 x 10(44) erg s(-1).
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  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
  • 2008
  • Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
  • Forskningsöversikt (refereegranskat)abstract
    • Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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  • Palmqvist, Sebastian, et al. (författare)
  • An accurate fully automated panel of plasma biomarkers for Alzheimer's disease
  • 2023
  • Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:4, s. 1204-1215
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction There is a great need for fully automated plasma assays that can measure amyloid beta (A beta) pathology and predict future Alzheimer's disease (AD) dementia. Methods Two cohorts (n = 920) were examined: Panel A+ (n = 32 cognitively unimpaired [CU], n = 106 mild cognitive impairment [MCI], and n = 89 AD) and BioFINDER-1 (n = 461 CU, n = 232 MCI). Plasma A beta 42/A beta 40, phosphorylated tau (p-tau)181, two p-tau217 variants, ApoE4 protein, neurofilament light, and GFAP were measured using Elecsys prototype immunoassays. Results The best biomarker for discriminating A beta-positive versus A beta-negative participants was A beta 42/A beta 40 (are under the curve [AUC] 0.83-0.87). Combining A beta 42/A beta 40, p-tau181, and ApoE4 improved the AUCs significantly (0.90 to 0.93; P< 0.01). Adding additional biomarkers had marginal effects (Delta AUC <= 0.01). In BioFINDER, p-tau181, p-tau217, and ApoE4 predicted AD dementia within 6 years in CU (AUC 0.88) and p-tau181, p-tau217, and A beta 42/A beta 40 in MCI (AUC 0.87). Discussion The high accuracies for A beta pathology and future AD dementia using fully automated instruments are promising for implementing plasma biomarkers in clinical trials and clinical routine.
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  • Schetelig, J, et al. (författare)
  • Haplotype Motif-Based Models for KIR-Genotype Informed Selection of Hematopoietic Cell Donors Fail to Predict Outcome of Patients With Myelodysplastic Syndromes or Secondary Acute Myeloid Leukemia
  • 2021
  • Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 11, s. 584520-
  • Tidskriftsartikel (refereegranskat)abstract
    • Results from registry studies suggest that harnessing Natural Killer (NK) cell reactivity mediated through Killer cell Immunoglobulin-like Receptors (KIR) could reduce the risk of relapse after allogeneic Hematopoietic Cell Transplantation (HCT). Several competing models have been developed to classify donors as KIR-advantageous or disadvantageous. Basically, these models differ by grouping donors based on distinct KIR–KIR–ligand combinations or by haplotype motif assignment. This study aimed to validate different models for unrelated donor selection for patients with Myelodysplatic Syndromes (MDS) or secondary Acute Myeloid Leukemia (sAML). In a joint retrospective study of the European Society for Blood and Marrow Transplantation (EBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR) registry data from 1704 patients with secondary AML or MDS were analysed. The cohort consisted mainly of older patients (median age 61 years) with high risk disease who had received chemotherapy-based reduced intensity conditioning and anti-thymocyte globulin prior to allogeneic HCT from well-matched unrelated stem cell donors. The impact of the predictors on Overall Survival (OS) and relapse incidence was tested in Cox regression models adjusted for patient age, a modified disease risk index, performance status, donor age, HLA-match, sex-match, CMV-match, conditioning intensity, type of T-cell depletion and graft type. KIR genes were typed using high-resolution amplicon-based next generation sequencing. In univariable and multivariable analyses none of the models predicted OS and the risk of relapse consistently. Our results do not support the hypothesis that optimizing NK-mediated alloreactivity is possible by KIR-genotype informed selection of HLA-matched unrelated donors. However, in the context of allogeneic transplantation, NK-cell biology is complex and only partly understood. KIR-genes are highly diverse and current assignment of haplotype motifs based on the presence or absence of selected KIR genes is over-simplistic. As a consequence, further research is highly warranted and should integrate cutting edge knowledge on KIR genetics, and NK-cell biology into future studies focused on homogeneous groups of patients and treatment modalities.
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  • Aus, Gunnar, 1958, et al. (författare)
  • EAU Guidelines on Prostate Cancer.
  • 2005
  • Ingår i: Eur Urol. - : Elsevier BV. ; 48:4, s. 546-551
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The first summary of the European Association of Urology (EAU) guidelines on prostate cancer was published in 2001. These guidelines have been continuously updated since many important changes affecting the clinical management of patients with prostate cancer have occurred over the past years. The aim of this paper is to present a summary of the 2005 update of the EAU guidelines on prostate cancer. Methods: A literature review of the new data has been performed by the working panel. The guidelines have been updated and level of evidence/grade of recommendation added to the text. This enables readers to better understand the quality of the data forming the basis of the recommendations. Results: A full version is available at the EAU Office or at www.uroweb.org. Systemic prostate biopsies under ultrasound guidance is the preferred diagnostic method and the use of periprostatic injection of a local anaesthetic can significantly reduce pain/discomfort associated with the procedure. Active treatment (surgery or radiation) is mostly recommended for patients with localized disease and a long life expectancy with radical prostatectomy being the only treatment evaluated in a randomized controlled trial. Follow-up is at large based on prostate specific antigen (PSA) and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy has become an option for selected patients with hormone refractory prostate cancer. Conclusion: The knowledge in the field of prostate cancer is rapidly changing. These EAU guidelines on prostate cancer summarize the most recent findings and put them into clinical practice.
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  • Khuyagbaatar, J., et al. (författare)
  • 48Ca+249Bk Fusion Reaction Leading to Element Z=117: Long-Lived α-Decaying 270Db and Discovery of 266Lr
  • 2014
  • Ingår i: Physical Review Letters. - 1079-7114. ; 112:17
  • Tidskriftsartikel (refereegranskat)abstract
    • The superheavy element with atomic number Z=117 was produced as an evaporation residue in the 48Ca+249Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-μs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope 294-117 and its decay products. A hitherto unknown α-decay branch in 270Db (Z=105) was observed, which populated the new isotope 266Lr (Z=103). The identification of the long-lived (T1/2=1.0+1.9−0.4 h) α-emitter 270Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an “island of stability.”
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  • Khuyagbaatar, J., et al. (författare)
  • Fission in the landscape of heaviest elements: Some recent examples
  • 2016
  • Ingår i: Nobel Symposium NS 160 – Chemistry and Physics of Heavy and Superheavy Elements. - : EDP Sciences. - 9782759890118 ; 131
  • Konferensbidrag (refereegranskat)abstract
    • The fission process still remains a main factor that determines the stability of the atomic nucleus of heaviest elements. Fission half-lives vary over a wide range, 10^−19 to 10^24 s. Present experimental techniques for the synthesis of the superheavy elements that usually measure α-decay chains are sensitive only in a limited range of half-lives, often 10^5 to 10^3 s. In the past years, measurement techniques for very short-lived and very long-lived nuclei were significantly improved at the gas-filled recoil separator TASCA at GSI Darmstadt. Recently, several experimental studies of fission-related phenomena have successfully been performed. In this paper, results on 254−256Rf and 266Lr are presented and corresponding factors for retarding the fission process are discussed.
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  • Khuyagbaatar, J., et al. (författare)
  • Fusion reaction 48Ca + 249Bk leading to formation of the element Ts (Z=117)
  • 2019
  • Ingår i: Physical Review C. - 2469-9985. ; 99:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The heaviest currently known nuclei, which have up to 118 protons, have been produced in 48Ca induced reactions with actinide targets. Among them, the element tennessine (Ts), which has 117 protons, has been synthesized by fusing 48Ca with the radioactive target 249Bk, which has a half-life of 327 d. The experiment was performed at the gas-filled recoil separator TASCA. Two long and two short α decay chains were observed. The long chains were attributed to the decay of 294Ts. The possible origin of the short-decay chains is discussed in comparison with the known experimental data. They are found to fit with the decay chain patterns attributed to 293Ts. The present experimental results confirm the previous findings at the Dubna Gas-Filled Recoil Separator on the decay chains originating from the nuclei assigned to Ts.
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  • Khuyagbaatar, J., et al. (författare)
  • New Short-Lived Isotope 221U and the Mass Surface Near N=126
  • 2015
  • Ingår i: Physical Review Letters. - 1079-7114. ; 115:24
  • Tidskriftsartikel (refereegranskat)abstract
    • Two short-lived isotopes 221U and 222U were produced as evaporation residues in the fusion reaction 50Ti+176Yb at the gas-filled recoil separator TASCA. An α decay with an energy of Eα=9.31(5) MeV and half-life T1/2=4.7(7) μs was attributed to 222U. The new isotope 221U was identified in α-decay chains starting with Eα=9.71(5) MeV and T1/2=0.66(14) μs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.
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  • Khuyagbaatar, J., et al. (författare)
  • Search for elements 119 and 120
  • 2020
  • Ingår i: Physical Review C. - 2469-9985. ; 102:6
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for production of the superheavy elements with atomic numbers 119 and 120 was performed in the 50Ti+249Bk and 50Ti+249Cf fusion-evaporation reactions, respectively, at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. Over four months of irradiation, the 249Bk target partially decayed into 249Cf, which allowed for a simultaneous search for both elements. Neither was detected at cross-section sensitivity levels of 65 and 200 fb for the 50Ti+249Bk and 50Ti+249Cf reactions, respectively, at a midtarget beam energy of Elab = 281.5 MeV. The nonobservation of elements 119 and 120 is discussed within the concept of fusion-evaporation reactions including various theoretical predictions on the fission-barrier heights of superheavy nuclei in the region of the island of stability.
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  • Landeiro, F, et al. (författare)
  • Measuring quality of life of people with predementia and dementia and their caregivers: a systematic review protocol
  • 2018
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 8:3, s. e019082-
  • Tidskriftsartikel (refereegranskat)abstract
    • Dementia is the fastest growing major cause of disability globally and may have a profound impact on the health-related quality of life (HRQoL) of both the patient with dementia and those who care for them. This review aims to systematically identify and synthesise the measurements of HRQoL for people with, and their caregivers across the full spectrum of, dementia from its preceding stage of predementia to end of life.Methods and analysisA systematic literature review was conducted in Medical Literature Analysis and Retrieval System Online , ExcerptaMedicadataBASE, Cochrane Database of Systematic Reviews , Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effect, National Health Service Economic Evaluation Database and PsycINFO between January 1990 and the end of April 2017. Two reviewers will independently assess each study for inclusion and disagreements will be resolved by a third reviewer. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed with the Effective Public Health Practice Project quality assessment tool. HRQoL measurements will be presented separately for people with dementia and caregivers by instrument used and, when possible, HRQoL will be reported by disease type and stage of the disease. Descriptive statistics of the results will be provided. A narrative synthesis of studies will also be provided discussing differences in HRQoL measurements by instrument used to estimate it, type of dementia and disease severity.Ethics and disseminationThis systematic literature review is exempt from ethics approval because the work is carried out on published documents. The findings of the review will be disseminated in a related peer-reviewed journal and presented at conferences. They will also contribute to the work developed in the Real World Outcomes across the Alzheimer’s disease spectrum for better care: multimodal data access platform (ROADMAP).Trial registration numberCRD42017071416.
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  • Landeiro, F, et al. (författare)
  • Resource utilisation and costs in predementia and dementia: a systematic review protocol
  • 2018
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 8:1, s. e019060-
  • Tidskriftsartikel (refereegranskat)abstract
    • Dementia is the fastest growing major cause of disability globally with a mounting social and financial impact for patients and their families but also to health and social care systems. This review aims to systematically synthesise evidence on the utilisation of resources and costs incurred by patients and their caregivers and by health and social care services across the full spectrum of dementia, from its preceding preclinical stage to end of life. The main drivers of resources used and costs will also be identified.Methods and analysisA systematic literature review was conducted in MEDLINE, EMBASE, CDSR, CENTRAL, DARE, EconLit, CEA Registry, TRIP, NHS EED, SCI, RePEc and OpenGrey between January 2000 and beginning of May 2017. Two reviewers will independently assess each study for inclusion and disagreements will be resolved by a third reviewer. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed with the Effective Public Health Practice Project quality assessment tool. The reporting of costing methodology will be assessed using the British Medical Journal checklist. A narrative synthesis of all studies will be presented for resources used and costs incurred, by level of disease severity when available. If feasible, the data will be synthesised using appropriate statistical techniques.Ethics and disseminationIncluded articles will be reviewed for an ethics statement. The findings of the review will be disseminated in a related peer-reviewed journal and presented at conferences. They will also contribute to the work developed in the Real World Outcomes across the Alzheimer’s disease spectrum for better care: multi-modal data access platform (ROADMAP).Trial registration numberCRD42017071413.
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  • Yuan, Ning, et al. (författare)
  • In situ XAS study of the local structure and oxidation state evolution of palladium in a reduced graphene oxide supported Pd(ii) carbene complex during an undirected C-H acetoxylation reaction
  • 2019
  • Ingår i: Catalysis Science and Technology. - : Royal Society of Chemistry (RSC). - 2044-4753 .- 2044-4761. ; 9:8, s. 2025-2031
  • Tidskriftsartikel (refereegranskat)abstract
    • In situ X-ray absorption spectroscopy (XAS) investigations have been performed to provide insights into the reaction mechanism of a palladium(ii) catalyzed undirected C-H acetoxylation reaction in the presence of an oxidant. A Pd(ii) N-heterocyclic carbene complex π-stacked onto reduced graphene oxide (rGO) was used as the catalyst. The Pd speciation during the catalytic process was examined by XAS, which revealed a possible mechanism over the course of the reaction. Pd(ii) complexes in the as-synthesized catalyst first go through a gradual ligand substitution where chloride ions bound to Pd(ii) are replaced by other ligands with a mean bond distance to Pd matching Pd-C/N/O. Parallel to this the mean oxidation state of Pd increases indicating the formation of Pd(iv) species. At a later stage, a fraction of the Pd complexes start to slowly transform into Pd nanoclusters. The mean average oxidation state of Pd decreases to the initial state at the end of the experiment which means that comparable amounts of Pd(0) and Pd(iv) are present. These observations from heterogeneous catalysis are in good agreement with its homogeneous analog and they support a Pd(ii)-Pd(iv)-Pd(ii) reaction mechanism.
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  • Yuan, Ning, et al. (författare)
  • In Situ XAS Study of the Local Structure and Oxidation State Evolutions of Palladium in a Reduced Graphene Oxide Supported Pd(II) Carbene Complex during an Undirected C−H Acetoxylation Reaction
  • 2019
  • Ingår i: Catalysis Science & Technology. - 2044-4753 .- 2044-4761. ; 9:8, s. 2025-2031
  • Tidskriftsartikel (refereegranskat)abstract
    • In situ X-ray absorption spectroscopy (XAS) investigations have been performed to provide insights into the reaction mechanism of a palladium(II) catalyzed undirected C–H acetoxylation reaction in the presence of an oxidant. A Pd(II) N-heterocyclic carbene complex p-stacked onto reduced graphene oxide (rGO) was used as catalyst. The Pd speciation during the catalytic process was examined by XAS, which revealed a possible mechanism over the course of the reaction. Pd(II) complexes in the as-synthesized catalyst first go through a gradual ligand substitution where chloride ions bound to Pd(II) are replaced by other ligands with a bond distance to Pd corresponding to carbon, nitrogen and/or oxygen (L). Parallel to this the mean oxidation state of Pd increases indicating the formation of Pd(IV) species. At a later stage, a fraction of the Pd complexes start to slowly transform into Pd nanoclusters. The mean average oxidation state of Pd decreases to the initial state at the end of the experiment which means that comparable amounts of Pd(0) and Pd(IV) are present. These observations from heterogeneous catalysis are in good agreement with its homogeneous analog and they support a Pd(II)-Pd(IV)-Pd(II) reaction mechanism.
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