In 2015, allegations of research data manipulation concerning the three papers first appeared on PubPeer. Dr. Tessier-Lavigne assessed these issues in the fall of 2015. He stated to the Panel that he initially thought that some of the issues involved “beautification” while others potentially represented more serious instances of manipulation of research data. Over the ensuing months in 2016, based on a discussion Dr. Tessier-Lavigne observed on PubPeer, he came to recharacterize the latter set of issues (in the two Science papers) as attributable to a phenomenon known as “tiling” and caused by Adobe Acrobat software rather than manipulation of research data. Regarding this so-called “tiling” phenomenon (не ну это очевидный троллинг), Dr. Tessier-Lavigne and the Scientific Panel along with its forensic experts have had several discussions together both to understand Dr. Tessier-Lavigne’s view and to provide him with additional forensic perspectives. The Panel believes that Dr. Tessier-Lavigne sincerely held the belief (ванька дурак) in 2016 (and through 2023) that: (1) tiling was a valid forensic explanation for certain issues observed in the two Science ’01 papers, and (2) by applying that explanation, issues that would otherwise be deemed clearly improper could be properly recharacterized as “beautifications” or as non-issues. As has been conveyed to Dr. Tessier-Lavigne, following a thorough forensic consideration of the topic, the Panel and its forensic experts do not believe that tiling validly explains the underlying image manipulations present in at least some of the relevant figures. Дальше лучше. Nature ’09 made claims for a neurodegeneration pathway that, if borne out, could have had significant implications for Alzheimer’s disease research and therapeutics. […] the Panel has identified multiple problems with the Nature ’09 paper (. First, the Panel has concerns about the rigor of the process through which the science of the paper was developed, including regarding the degree of critical thinking and rigor applied to experimental design, evaluation, and characterization of reagents and data analysis during the research process. In particular: the research for the paper made use of what were, in fact, crude culture supernatant fractions and an insufficiently characterized and insufficiently pure recombinant N-terminal fragment preparation of APP. The Nature ’09 paper described the APP as having been “affinity purified” and Dr. Tessier-Lavigne has maintained to the Panel that he regarded the APP as being sufficiently purified to the best of his knowledge at the time. However, although the Nature ’09 paper described the APP as having been “affinity purified,” in one of the follow-on papers to Nature ’09, Dr. Tessier-Lavigne and his co-authors themselves write: The prior study [(Nature ’09)] had used N-APP from two sources, commercial (Thermo Fisher) and in-house (Genentech), which gave consistent results. However, both preparations were only partially purified and biochemical analyses revealed them to contain contaminants and aggregated material (data not shown). To guard against nonspecific effects, we set out to obtain purer and nonaggregated N-APP. As purification proceeded, we unexpectedly found that the prodegenerative effects of N-APP were lost (ничоси, Михалыч, представляешь, оказывается чистый реагент ведет себя не так, как раствор грязного носка и топора), as was binding to the DR6 ectodomain (fused to alkaline phosphatase: DR6-AP) observed by ELISA (Fig. 7E). One possibility is that the binding and functional effects seen with earlier material were caused by aggregates that may have accumulated during partial purification; an alternative is that a contaminant in the partially purified material contributed to activity and/or binding. (это точно Nature?)