Do the Frankenstein, or how to achieve better out-of-distribution performance with manifold mixing model soup

The standard recipe applied in transfer learning is to finetune a pretrained model on the task-specific dataset with different hyperparameter settings and pick the model with the highest accuracy on the validation dataset. Unfortunately, this leads to models which do not perform well under distribution shifts, e.g. when the model is given graphical sketches of the object as input instead of photos. In order to address this, we propose the manifold mixing model soup, an algorithm which mixes together the latent space manifolds of multiple finetuned models in an optimal way in order to generate a fused model. We show that the fused model gives significantly better out-of-distribution performance (+3.5 % compared to best individual model) when finetuning a CLIP model for image classification. In addition, it provides also better accuracy on the original dataset where the finetuning has been done.Comment: Accepted for IMVIP 2023 conferenc

The Concurrent Prevalence of Modernism and Romanticism as seen in the Operas Performed between the World Wars and Exemplified in Ernst Krenek’s Jonny Spielt Auf

Ernst Krenek’s 1927 opera Jonny Spielt Auf represents Zeitoper, or “opera of the times”. The opera’s story line and characters symbolize Krenek’s internal debate of a divided artistic world between all that is modern and innovative and the older mindset of romanticism, both of which he used in his compositions. This dissertation intends to peer into Krenek’s world and influences of the 1920s to consider the symbols in the opera that represent Modernism and Romanticism. The Golden Age of the Weimar Republic occurred from 1924 to 1929, between the World Wars. During this time, Austrian and German composers had the funds to publish their works and have their operas performed. Performers from America, including African American jazz bands, were making their first tours to Europe and had a large impact on European composers. During the Third Reich, beginning in 1933, the Romanticists were honored and praised by the Nazi regime while the Modernists’ music, along with jazz and the music of Jewish composers, was banned and labeled in an exhibit as Entartete Musik or Degenerate Music. The poster for Jonny Spielt Auf was used as the poster of this exhibit because of the character Jonny in the opera. Though Jonny was performed by a white man in blackface, he represents an African American jazz musician. Max Spilcker, the original singer to play Jonny, had relations to Hitler, creating a possible tie to the Entartete Musik poster. The symbols found in an underlying story of Jonny Spielt Auf further reflect Zeitoper. The story centers around a composer, Max, who represents Krenek. Daniello, a virtuoso violinist, represents Romanticism, while Jonny, a jazz violinist, represents Modernism. Krenek uses both styles of music in his score. The first clue in the opera of Daniello and Jonny’s contrasting ideals vii is found in the violin solo from Act 1, Scene 3 labeled “Tango”. The solo intertwines with a saxophone solo as if to demonstrate an interplay between the two characters. Every moment of the opera has a double meaning related to Krenek’s world of the 1920s, with much of its symbolism yet to be analyzed

DAVID D2.2: Analysis of loss modes in preservation systems

This is a report on the way in which loss and damage to digital AV content occurs for different content types, AV data carriers and preservation systems.Three different loss modes have been identified, and each has been analysed in terms of existing solutions and longterm effects. This report also includes an in-depth treatment of format compatibility (interoperability issues), format resilience to carrier degradation and format resilience to corruption

ADAM9 inhibition increases membrane activity of ADAM10 and controls α-secretase processing of amyloid precursor protein

Prodomains of A disintegrin and metalloproteinase (ADAM) metallopeptidases can act as highly specific intra- and intermolecular inhibitors of ADAM catalytic activity. The mouse ADAM9 prodomain (proA9; amino acids 24–204), expressed and characterized from Escherichia coli, is a competitive inhibitor of human ADAM9 catalytic/disintegrin domain with an overall inhibition constant of 280 ± 34 nm and high specificity toward ADAM9. In SY5Y neuroblastoma cells overexpressing amyloid precursor protein, proA9 treatment reduces the amount of endogenous ADAM10 enzyme in the medium while increasing membrane-bound ADAM10, as shown both by Western and activity assays with selective fluorescent peptide substrates using proteolytic activity matrix analysis. An increase in membrane-bound ADAM10 generates higher levels of soluble amyloid precursor protein α in the medium, whereas soluble amyloid precursor protein β levels are decreased, demonstrating that inhibition of ADAM9 increases α-secretase activity on the cell membrane. Quantification of physiological ADAM10 substrates by a proteomic approach revealed that substrates, such as epidermal growth factor (EGF), HER2, osteoactivin, and CD40-ligand, are increased in the medium of BT474 breast tumor cells that were incubated with proA9, demonstrating that the regulation of ADAM10 by ADAM9 applies for many ADAM10 substrates. Taken together, our results demonstrate that ADAM10 activity is regulated by inhibition of ADAM9, and this regulation may be used to control shedding of amyloid precursor protein by enhancing α-secretase activity, a key regulatory step in the etiology of Alzheimer disease.National Institutes of Health (U.S.) (Grant R01EB010246)National Institutes of Health (U.S.) (Grant R01GM081336)Heptagon Fund (London, England)Cancer Research UKWhitehead FoundationDuke University. School of Medicine (Bridge Funding Program)Germany. Bundesministerium für Bildung und ForschungChina (National Fellowship from the Chinese Scholarship Council)Florida State Universit

Increased TIMP-3 expression alters the cellular secretome through dual inhibition of the metalloprotease ADAM10 and ligand-binding of the LRP-1 receptor

The tissue inhibitor of metalloproteinases-3 (TIMP-3) is a major regulator of extracellular matrix turnover and protein shedding by inhibiting different classes of metalloproteinases, including disintegrin metalloproteinases (ADAMs). Tissue bioavailability of TIMP-3 is regulated by the endocytic receptor low-density-lipoprotein receptor-related protein-1 (LRP-1). TIMP-3 plays protective roles in disease. Thus, different approaches have been developed aiming to increase TIMP-3 bioavailability, yet overall effects of increased TIMP-3 in vivo have not been investigated. Herein, by using unbiased mass-spectrometry we demonstrate that TIMP-3-overexpression in HEK293 cells has a dual effect on shedding of transmembrane proteins and turnover of soluble proteins. Several membrane proteins showing reduced shedding are known as ADAM10 substrates, suggesting that exogenous TIMP-3 preferentially inhibits ADAM10 in HEK293 cells. Additionally identified shed membrane proteins may be novel ADAM10 substrate candidates. TIMP-3-overexpression also increased extracellular levels of several soluble proteins, including TIMP-1, MIF and SPARC. Levels of these proteins similarly increased upon LRP-1 inactivation, suggesting that TIMP-3 increases soluble protein levels by competing for their binding to LRP-1 and their subsequent internalization. In conclusion, our study reveals that increased levels of TIMP-3 induce substantial modifications in the cellular secretome and that TIMP-3-based therapies may potentially provoke undesired, dysregulated functions of ADAM10 and LRP-1