Sznajder, J.; Ciechanover, A. Personalized Medicine. The Road Ahead. Am. J. Respir. Crit. Care Med. 2012, 186, 945–947. [ Google Scholar] [ CrossRef] [ PubMed] Kryukova, O.V.; Tikhomirova, V.E.; Golukhova, E.Z.; Evdokimov, V.V.; Kalantarov, G.F.; Trakht, I.N.; Schwartz, D.E.; Dull, R.O.; Gusakov, A.V.; Uporov, I.V.; et al. Tissue Specificity of human angiotensin I-converting enzyme. PLoS ONE 2015, 10, e0143455. [ Google Scholar] [ CrossRef] [ PubMed] Skirgello, O.E.; Balyasnikova, I.V.; Binevski, P.V.; Sun, Z.-L.; Baskin, I.I.; Palyulin, V.A.; Nesterovitch, A.B.; Albrecht, R.F.; Kost, O.A.; Danilov, S.M. Inhibitory antibodies to human angiotensin-converting enzyme: Fine epitope mapping and mechanism of action. Biochemistry 2006, 45, 4831–4847. [ Google Scholar] [ CrossRef] [ PubMed] König, I.R.; Fuchs, O.; Hansen, G.; von Mutius, E.; Kopp, M.V. What is precision medicine? Eur. Respir. J. 2017, 50, 1700391. [ Google Scholar] [ CrossRef] If the series had continued, the production team's intent was to have Ace eventually enter the Prydonian Academy on the Doctor's home planet of Gallifrey and train to be a Time Lord. [7] The story Ice Time by Marc Platt, in which this would happen, was never made. [10] When the Seventh Doctor is next seen in the 1996 Doctor Who television movie, he is travelling alone, with no reference made as to what had happened to Ace. [8] In " The Power of the Doctor" (2022), it is said that Ace and the Doctor had some sort of "fallout" which led to her leaving, although what exactly happened is never clarified.

What the Doctor is aware of, but Ace is not, is that her arrival on Iceworld was no accident but part of a larger scheme stretching across the centuries and conceived by Fenric, [6] an evil that had existed since the beginning of the universe. Ace is a "Wolf of Fenric", one of many descendants of a Norseman tainted with Fenric's genetic instructions to help free it from its ancient prison so it can evolve humans into the Vampiric Haemovores, and a pawn in the complex game between it and the Doctor. After Fenric is defeated in 1943, Ace continues to journey with the Doctor. [7] At one point in the story, Ace offers to distract a guard so that the Doctor can free a prisoner. When the Doctor asks how she plans to divert the guard's attention she replies that she is "not a little girl". She proceeds to lead the guard away from his post by intriguing him with a combination of slightly suggestive innuendo towards the guard and cryptic musings about the Doctor's machinations. The scene suggests that she is aware of both her developed sexuality and the Doctor's manipulative tendencies. Other spin-off media give contradictory versions of Ace's eventual fate. The comic strip in Doctor Who Magazine has Ace killed off just prior to the events of the 1996 television movie ( Ground Zero, DWM #238-#242). In the webcast audio play Death Comes to Time, Ace inherits the mantle of the Time Lords when they become extinct. Using this genotype-dependent expression pattern as a tracer, we tested if the primary source of circulating ACE is the lung in humans. To do so, we tested ACE levels in serum and lung samples of the same patients in parallel, using techniques developed in our laboratory in the past years [ 17, 18, 20, 27, 28]. Patients with the DD genotype had significantly higher circulating ACE concentrations and activities than patients with the ACE II genotype, while patients with the ACE ID genotype showed intermediate values confirming earlier reports. However, we did not find any correlation of lung tissue ACE expression or activity with the ACE I/D genotype. This finding suggests that ACE expression in the lungs is independent of ACE I/D genotype, and consequently, the genotype-dependent serum ACE secretion must have an alternative source of ACE. 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] Ace is a 16-year-old human who first appears in the 1987 serial Dragonfire, where she is working as a waitress in the frozen food retail complex of Iceworld on the planet Svartos. [8] She had been a troubled teen on Earth, having been expelled from school for blowing up the art room as a "creative statement". Gifted in chemistry (despite failing the subject at O-level), she was in her room experimenting with the extraction of nitroglycerin from gelignite when an explosion (later revealed to be a time-storm created by Fenric) swept her up and transported her to Iceworld, many years in the future. [6] There, she meets the Doctor and his companion Mel. When Mel leaves the Doctor at the conclusion of the serial, he offers to take Ace with him in the TARDIS, and she happily accepts.ACE extraction method—A role for detergents. Human lung tissue samples were homogenized in SDS, Triton-X-100 and Triton-X-114 containing buffers. Final concentrations in activity measurements are shown on the x-axes (note, homogenates were two-fold diluted in the activity measurement mixture). The homogenates were centrifuged and the supernatants were collected, diluted to 1 mg/mL (with the same buffer, containing the indicated detergents). ACE concentration was measured by ELISA ( A), while activity was measured by a kinetic assay ( B). The ratio of the activity and concentration values yielded the specific activity, which is shown in ( C). In some cases, the homogenization procedure was repeated using the ACE depleted pellets after homogenization. The number of these repeated extraction cycles is indicated in panels ( D, E). In these cases, the ACE activity was expressed as the percentage of the first supernatants (( D): buffer without detergent, ( E): Buffer with 0.3% Triton-X-100). Symbols ( A– C) and bars ( D, E) represent the mean, error bars show the S.E.M. of n = 5–9. Significant differences ( p< 0.05) are labelled by the asterisks. Minucci, G.C.A.; Zuppi, C.; Capoluongo, E. Gilbert and Crigler-Najjar syndromes: An update of the UDP-glucoronosyltransferase 1a1 (UGT1A1) gene mutation database. Blood Cells Mol. Dis. 2013, 50, 273–280. [ Google Scholar] Okuneva, E.G.; Kozina, A.A.; Baryshnikova, N.V.; Krasnenko, A.Y.; Tsukanov, K.; Klimchuk, O.I.; Surkova, E.I.; Ilinsky, V.V. A novel elastin gene frameshift mutation in a Russian family with cutis laxa: A case report. BMC Dermatol. 2019, 19, 4. [ Google Scholar] [ CrossRef] [ PubMed] Lieberman, J. Elevation of serum angiotensin-converting enzyme level in sarcoidosis. Am. J. Med. 1975, 59, 365–372. [ Google Scholar] [ CrossRef] A recent report on lung ACE reported tissue ACE expression decreases in lung cancer [ 23]. Indeed, a negative correlation between lung cancer and circulating ACE activity was shown half a century ago, in a limited number of patients [ 32]. This study suggested that if lung microcapillaries are being lost in the tumor, then circulating ACE activities will decline. However, none of the previous studies attempted to directly test the relationships between circulating and lung tissue ACE expressions. To the best of our knowledge, this report is the first to do so in a fairly large human population.

Collis, Clark (17 April 2022). "The trailer for Jodie Whittaker's final episode of 'Doctor Who' reveals returning cast members". Entertainment Weekly . Retrieved 17 April 2022. Kost, O.A.; Grinshtein, S.V.; Nikolskaya, I.; Shevchenko, A.; Binevski, P.V. Purification of soluble and membrane forms of somatic angiotensin-converting enzyme by cascade affinity chromatography. Biochemistry 1997, 62, 321–328. [ Google Scholar] Danilov, S.M.; Tikhomirova, V.E.; Metzger, R.; Naperova, I.A.; Bukina, T.M.; Goker-Alpan, O.; Tayebi, N.; Gayfullin, N.M.; Schwartz, D.E.; Samokhodskaya, L.M.; et al. ACE phenotyping in Gaucher disease. Mol. Genet Metab. 2018, 123, 501–510. [ Google Scholar] [ CrossRef] In 2018, Ace was confirmed to appear in Big Finish Production's audio drama based on Doctor Who spin-off Class, with Aldred reprising her role alongside the show's main cast. [13] The story released that August. Watchko, J.F.; Tiribelli, C. Bilirubin-induced neurologic damage-mechanisms and management approaches. N. Engl. J. Med. 2013, 369, 2021–2030. [ Google Scholar] [ CrossRef]Balyasnikova, I.V.; Skirgello, O.E.; Binevski, P.V.; Nesterovitch, A.B.; Albrecht, R.F.; Kost, O.A.; Danilov, S.M. Monoclonal antibodies 1G12 and 6A12 to the N-domain of human angiotensin-converting enzyme: Fine epitope mapping and antibody-based method for revelation and quantification of ACE inhibitors in the human blood. J. Proteome Res. 2007, 6, 1580–1594. [ Google Scholar] [ CrossRef] [ PubMed] Ace is a fictional character played by Sophie Aldred in the long-running British science fiction television series Doctor Who. [3] A 20th-century Earth teenager from the London suburb of Perivale, she is a companion of the Seventh Doctor and was a regular in the series from 1987 to 1989. [4] She is considered one of the Doctor's most popular companions. [5]