Ace's relationship with the Doctor remains strained for some time, boiling over in Blood Heat when the Doctor destroys an unstable parallel Earth (where Manisha is still alive) and under the influence of an alien creature she stabs him through one of his hearts in The Left-Handed Hummingbird. In No Future (also by Cornell) the Meddling Monk tries to manipulate her into betraying the Doctor, which she seemingly does, again stabbing him and leaving him alone on an ice planet. In reality she stabbed him with a pantomime knife from the TARDIS wardrobe and she is playing her own game (partly to teach him what it feels like to be manipulated). When the Monk and his chained Chronovore offer her a chance to return Jan to life, she refuses and rejoins the TARDIS crew, her issues with the Doctor resolved. In Set Piece by Kate Orman, Ace becomes stranded in Ancient Egypt and comes to realise that she can survive without the Doctor, but that she also increasingly sees the world as he does. At the book's end she leaves the Doctor again to become Time's Vigilante, using a short-range time hopper mounted on a motorcycle to patrol a particular segment of time; in effect doing what the Doctor does, but on a smaller scale. She appears in later books, notably Head Games, Happy Endings, and Lungbarrow. Our data suggest that the source of circulating ACE is independent of lung capillaries. In line with that, the human heart was identified as an alternative source for circulating ACE. Additional ACE expressing and secreting cells can also be found in the apical surface of epithelial cells in the proximal tubule of kidney, the mucosa of small intestine, the syncytial trophoblast of placenta and the choroid plexus, in addition to various regions within the central nervous system [ 24]. Moreover, ACE was also found to be expressed by macrophages [ 33]. While the role of these potential ACE sources in the circulating ACE levels is unknown, it is well established that circulating ACE level increases in sarcoidosis [ 34]. We also confirmed elevated circulating ACE levels in patients with sarcoidosis and proposed that it can be used as a biomarker for sarcoidosis [ 27, 28]. Using a similar approach to ours, an independent study reported genotype-dependent ACE expression in the human heart [ 15] in full accordance with our findings in the present study, suggestive of a relationship between serum and cardiac ACE activities. ACE I/D Polymorphism as a Quantitative Trait Locus for ACE Expression in the Blood, but Not in the Lung

The molecular properties of a successful ACE inhibitor generally include low lipophilicity (with the exception of fosinopril) [ 11]. This indicates that the primary target of these drugs is the water-soluble (circulating) form of the enzyme. Accordingly, factors affecting circulating ACE activities have been implicated in the pathomechanism of cardiovascular disease. Circulating ACE concentration is controlled by a genetic polymorphism of the ACE gene (an insertion/deletion polymorphism, I/D polymorphism) [ 12], being implicated in systolic heart failure [ 13]. Gerber, P.; Muller, K. MAB, a generally applicable molecular force field for structure modelling in medicinal chemistry. J. Comput. Aided Mol. Des. 2015, 9, 251–268. [ Google Scholar] [ CrossRef] In 2020, BBC Books published At Childhood's End ( ISBN 9781785944994), a novel by Aldred featuring Ace, decades after her travels with the Doctor and now running the "A Charitable Earth" charity. The novel also features the Thirteenth Doctor and her companions. Like the charity, the title of the novel forms the acronym "ACE".a b c Scott, Cavan; Wright, Mark (2013). Whoology: Doctor Who the Official Miscellany. BBC Books. pp.146–147. ISBN 9781849906197. Popova, I.A.; Lubbe, L.; Petukhov, P.A.; Kalantarov, G.F.; Trakht, I.N.; Chernykh, E.R.; Leplina, O.Y.; Lyubimov, A.V.; Garcia, J.G.; Dudek, S.M.; et al. Epitope mapping of novel monoclonal antibodies to human angiotensin I-converting enzyme. Protein Sci. 2021, 30, 1577–1593. [ Google Scholar] [ CrossRef]

Wei, L.; Gelas, F.A.; Soubrier, F.; Michaud, A.; Corvol, P.; Clauser, E. Expression and characterization of recombinant human angiotensin I-converting enzyme. Evidence for a C-terminal transmembrane anchor and for a proteolytic processing of the secreted recombinant and plasma enzymes. J. Biol. Chem. 1991, 266, 5540–5546. [ Google Scholar] [ CrossRef] Danilov, S.M.; Balyasnikova, I.V.; Danilova, A.S.; Naperova, I.A.; Arablinskaya, N.E.; Borisov, S.E.; Metzger, R.; Franke, F.E.; Schwartz, D.E.; Gachok, I.V.; et al. Conformational fingerprinting of the angiotensin-converting enzyme (ACE): Application in sarcoidosis. J. Proteome Res. 2010, 9, 5782–5793. [ Google Scholar] [ CrossRef] Dumoulin, M.; Kumita, J.R.; Dobson, C.M. Normal and aberrant biological self-assembly: Insights from studies of human lysozyme and its amyloidogenic variants. Acc. Chem. Res. 2006, 39, 603–610. [ Google Scholar] [ CrossRef]

Ace and the Seventh Doctor appeared twice more on television after Doctor Who was cancelled. The first occasion was in 1990, in a special episode of the BBC2 educational programme Search Out Science. In this episode, the Doctor acts as a quiz show host, asking questions about astronomy; Ace, K-9 and "Cedric, from the planet Glurk" are the contestants. The last appearance of Ace on British television was in the Dr Who TV special " The Power of the Doctor" (2022) in Jodie Whittaker's final appearance as the Doctor. Under the Doctor's tutelage, Ace fights the Daleks in Remembrance of the Daleks, the Cybermen in Silver Nemesis, encounters the all-powerful Gods of Ragnarok in The Greatest Show in the Galaxy, the sadistic torturer Kandy Man in The Happiness Patrol, and many other dangers. She also faces the ghosts of her own past in Ghost Light and The Curse of Fenric, coming to terms with them and, ironically, creating them in the latter case thanks to the paradoxes of time travel. Over time, she starts to mature into a confident young woman, and her brash exterior ceases to be a front. a b c d e McEwan, Cameron K. (2014). The Who's Who of Doctor Who. New York: Race Point Publishing. p.50. ISBN 9781937994709.