‘Creating unrealities’: rethinking mimesis as production of difference

This essay examines Costa Lima’s rehabilitation of mimesis as production of difference by locating its roots in psycho- and anthropogenesis. It traces how the mimetic cathexis of the body and of material objects as media of communicative action is gradually shifted onto language. This discussion contextualises Costa Lima’s investigations into mimesis and the control of the imaginary, and concludes by arguing that we abandon the traditional binary model of imitatio in favour of a triadic model. We might then conceptualize mimesis in terms of a model in which the triad subjectivity – art – reality corresponds, at a different level of abstraction, to the triad the imaginary – the fictional – the real. In such a triadic model, mimesis operates through a process of mutual differentiation: the negotiation and exchange that takes place between subjectivity and reality, or the imaginary and the real, alters both poles of the triad. In a successful literary transference art will reshape reality under the impact of subjectivity, and alter the boundaries of subjectivity in contact with reality. Mediated through the fictional, the imaginary will accordingly have a changing impact on the real and vice versa

Final report for the CORE Organic Plus funded project “Drying, Juices and Jams of Organic Fruit and Vegetables: what happens to Desired and Non-Desired compounds? FaVOR-DeNonDe” Period covered: 30 March 2015 - 29 March 2018

The main activity was related to the description of qualitative data on commonly consumed fruit (strawberry, plum, apple) and vegetables (tomato and sweet bell pepper) along some processing chains (jam, juices and dried products), pointing out the role of different sources of variability, such as the type of cultivation (Conventional, CONV or Organic, ORG), the different cultivars, the sampling year, and the type of processing. A particular attention has been paid on the type of processing, where the use of innovative plant was performed, in comparison with traditional or home-made processing typologies. This for the need, especially for local and small farmers, of small and simple plants to process agricultural products, in order to add value for their productions, for achieving high quality and safe products. For this scope three types of approaches for processing were used: - a miniaturized multifunctional processing line (MT), already validated in previous Projects, in comparison with home-made technique (HM) for jam strawberry production; - a pneumatic press, a rack-press and a belt-press compared for the production of apple juices; - an innovative drier, completely supplied by solar energy (SUN) compared with a traditional forced air oven-drier (OVEN) was used for the production of prunes, dried tomatoes and sweet bell peppers. The list of analyzed samples is shown on the Final Report Document: SCHEME OF ANALYZED SAMPLES (ORG is Organic, CONV is Conventional) The processed samples were produced in open field on two consecutive sampling years (2015 and 2016), on experimental fields. A third year of sampling was added, considering the evaluation made on raw products. Moreover, for tomato and sweet bell pepper, the production made from open fields of private organic growers, was considered, so obtaining samples in two consecutive years (2016 and 2017). Hence, a further comparison of the quality indexes was made on raw products in three consecutive years (2015, 2016 and 2017). The control samples were represented by the lyophilized material, generally referred as “raw” or “not treated” sample. The considered qualitative data regarded "Desired" and "Non Desired" compounds, being the desired ones those potentially healthy and tasty for humans, such as phytochemicals, antioxidants and volatiles, and the non desired some anti-nutritional traits, such as the mycotoxin patulin and the presence of allergens. The samples were also evaluated by their sensory properties, by using a trained panel. As for the allergen analysis, they were analyzed by indirect competitive ELISA for determination of Bet v 1-related protein, or pathogenesis-related proteins (PR-10), causing birch pollen related fruit allergies. A big amount of data was collected, with a consequent variability among them. The general consideration about desired compounds that can be made is that, if a well detectable difference in composition has been found in raw product, this difference was also retained in the processed one, with the processing technique strongly influencing the qualitative parameters of the final products. In this context, better results in terms of antioxidant presence were found for: - apple juices obtained from belt-press; - strawberry jams obtained with miniaturized small-scale plant; - prunes, tomatoes and sweet bell pepper obtained with oven drying. On the other hand, it has to be pointed out that processing methods causing a lower retention on the phytochemical contents often show a better response in term of sensory properties, as found in apple juices and in solar-dried samples of strawberries, plums and tomatoes. Some differences were found among the assayed cultivars, and, finally, among the comparison of the system of cultivation (ORG vs CONV). Specifically, the system of cultivation mainly influenced the antioxidant content in apples of traditional cultivars of Estonia obtained from aged plants; as for strawberry, it was found an higher amount of antioxidants in organic samples in one year of three, and a significant increase in ascorbic acid was found in the assayed local variety of organic bell pepper, in all three years, but not in the corresponding commercial hybrid. On the other hand, the plum cultivar Jubileum, assayed from Denmark and Norway in two years, resulted not adapted for organic cultivation for the content in ascorbic acid, constantly giving lower indexes in all samples in comparison with fruits from conventional cultivation. As regards the influence of the sampling years, in samples of apples, plums, tomatoes and sweet bell pepper, a tendency to an increase in phytochemicals and antioxidant indexes was detected in 2016 with respect to 2015 samples, due to the very different climate conditions of these two years. Interestingly, for the non desired traits, no clear relationship was found between the presence of patulin and allergens for the systems of cultivations, but significant variations were found with the difference in processing technique, with the sampling years and with the assayed cultivars. Interestingly, for some apple cultivars from Estonia low levels of the allergen Mald1 were detected. Concluding, the sources of variability among the analyzed samples gave, in order of influence, the following ranking: - 1. Processing techniques; - 2. Years of sampling; - 3. Cultivars; - 4. Growing methods

Pharmacokinetics and pharmacodynamics of thiopurines in an in\ua0vitro model of human hepatocytes: Insights from an innovative mass spectrometry assay

AIM: To apply an innovative LC-MS/MS method to quantify thiopurine metabolites in human hepatocytes and to associate them to cytotoxicity. METHODS: Immortalized human hepatocytes (IHH cells) were treated for 48 and 96 h, with 1.4 7 10-4 M azathioprine and 1.1 7 10-3 M mercaptopurine, concentrations corresponding to the IC50 values calculated after 96 h exposure in previous cytotoxicity analysis. After treatments, cells were collected for LC-MS/MS analysis to quantify 11 thiopurine metabolites with different level of phosphorylation and viable cells were counted by trypan blue exclusion assay to determine thiopurines in vitro effect on cell growth and survival. Statistical significance was determined by analysis of variance (ANOVA). RESULTS: Azathioprine and mercaptopurine had a significant time-dependent cytotoxic effect (p-value ANOVA = 0.012), with a viable cell count compared to controls of 55.5% and 67.5% respectively after 48 h and 23.7% and 36.1% after 96 h; no significant difference could be observed between the two drugs. Quantification of thiopurine metabolites evidenced that the most abundant metabolite was TIMP, representing 57.1% and 40.3% of total metabolites after 48 and 96 h. Total thiopurine metabolites absolute concentrations decreased over time: total mean content decreased from 469.9 pmol/million cells to 83.6 pmol/million cells (p-value ANOVA = 0.0070). However, considering the relative amount of thiopurine metabolites, TGMP content significantly increased from 11.4% cells to 26.4% (p-value ANOVA = 0.017). A significant association between thiopurine effects and viable cell counts could be detected only for MeTIMP: lower MeTIMP concentrations were associated with lower cell survival (p-value ANOVA = 0.011). Moreover, the ratio between MeTIMP and TGMP metabolites directly correlated with cell survival (p-value ANOVA = 0.037). CONCLUSION: Detailed quantification of thiopurine metabolites in a human hepatocytes model provided useful insights on the association between thioguanine and methyl-thioinosine nucleotides with cell viability

Elevated circulating Hsp70 levels are correlative for malignancies in different mammalian species

Circulating Hsp70 levels were determined in feline and porcine cohorts using two different ELISA systems. These comparative animal models of larger organisms often reflect diseases, and especially malignant tumors, better than conventional rodent models. It is therefore essential to investigate the biology and utility of tumor biomarkers in animals such as cats and pigs. In this study, levels of free Hsp70 in the blood of cats with spontaneously occurring tumors were detected using a commercial Hsp70 ELISA (R&D Systems). Sub-analysis of different tumor groups revealed that animals with tumors of epithelial origin presented with significantly elevated circulating Hsp70 concentrations. In addition to free Hsp70 levels measured with the R&D Systems Hsp70 ELISA, levels of exosomal Hsp70 were determined using the compHsp70 ELISA in pigs. Both ELISA systems detected significantly elevated Hsp70 levels (R&D Systems: median 24.9 ng/mL; compHsp70: median 44.2 ng/mL) in the blood of a cohort of APC$^{1311/+}$ pigs diagnosed with high-grade adenoma polyps, and the R&D Systems Hsp70 ELISA detected also elevated Hsp70 levels in animals with low-grade polyps. In contrast, in flTP53$^{R167H}$ pigs, suffering from malignant osteosarcoma, the compHsp70 ELISA (median 674.32 ng/mL), but not the R&D Systems Hsp70 ELISA (median 4.78 ng/mL), determined significantly elevated Hsp70 concentrations, indicating that in tumor-bearing animals, the dominant form of Hsp70 is of exosomal origin. Our data suggest that both ELISA systems are suitable for detecting free circulating Hsp70 levels in pigs with high-grade adenoma, but only the compHsp70 ELISA can measure elevated, tumor-derived exosomal Hsp70 levels in tumor-bearing animals

Double-soft limits of gluons and gravitons

Open Access, (c) The Authors. Article funded by SCOAP 3

Wege in die Ernährungszukunft der Schweiz - Leitfaden zu den grössten Hebeln und politischen Pfaden für ein nachhaltiges Ernährungssystem

Aus wissenschaftlicher Sicht ist klar: Unser Ernährungssystem ist nicht nachhaltig. Um unsere Lebens- und Wirtschaftsgrundlagen zu erhalten, braucht es eine Neuausrichtung über die gesamte Wertschöpfungskette. Diese ist gleichzeitig ein Schlüssel zur Erreichung der Agenda 2030 für nachhaltige Entwicklung. SDSN Schweiz hat das wissenschaftliche Gremium Ernährungszukunft Schweiz initiiert, um einen Wegweiser zu entwickeln. Er soll es der Schweiz erlauben, Chancen rechtzeitig anzupacken und unkontrollierbare Kostenfolgen zu vermeiden. Das wissenschaftliche Gremium hat international wegweisende Pionierarbeit geleistet. In einem interdisziplinären wissenschaftlichen Prozess wurde zum ersten Mal für ein Land ein umfassender Handlungspfad zur Neuausrichtung des Ernährungssystems im Einklang mit den Zielen für nachhaltige Entwicklung ausgearbeitet. Die beteiligten Forschenden schaffen damit eine wichtige Grundlage für die weitere politische Diskussion in der Schweiz und international

Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia

B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer. High hyperdiploidy (HHD) identifies the most frequent cytogenetic subgroup in childhood B-ALL. Although hyperdiploidy represents an important prognostic factor in childhood B-ALL, the specific chromosome gains with prognostic value in HHD-B-ALL remain controversial, and the current knowledge about the hierarchy of chromosome gains, clonal heterogeneity and chromosomal instability in HHD-B-ALL remains very limited. We applied automated sequential-iFISH coupled with single-cell computational modeling to identify the specific chromosomal gains of the eight typically gained chromosomes in a large cohort of 72 primary diagnostic (DX, n = 62) and matched relapse (REL, n = 10) samples from HHD-B-ALL patients with either favorable or unfavorable clinical outcome in order to characterize the clonal heterogeneity, specific chromosome gains and clonal evolution. Our data show a high degree of clonal heterogeneity and a hierarchical order of chromosome gains in DX samples of HHD-B-ALL. The rates of specific chromosome gains and clonal heterogeneity found in DX samples differ between HHD-B-ALL patients with favorable or unfavorable clinical outcome. In fact, our comprehensive analyses at DX using a computationally defined risk predictor revealed low levels of trisomies +18+10 and low levels of clonal heterogeneity as robust relapse risk factors in minimal residual disease (MRD)-negative childhood HHD-B-ALL patients: relapse-free survival beyond 5 years: 22.1% versus 87.9%, P < 0.0001 and 33.3% versus 80%, P < 0.0001, respectively. Moreover, longitudinal analysis of matched DX-REL HHD-B-ALL samples revealed distinct patterns of clonal evolution at relapse. Our study offers a reliable prognostic sub-stratification of pediatric MRD-negative HHD-B-ALL patients

Preparation and reactivity of diazoalkane complexes of ruthenium stabilised by an indenyl ligand

Diazoalkane complexes [Ru(η5-C9H7)(N2CAr1Ar2)(PPh3)L]BPh4 (1-3) [L = PPh3, P(OMe)3, P(OEt)3; Ar1 = Ar2 = Ph; Ar1 = Ph, Ar2 = p-tolyl; Ar1Ar2 = C12H8 fluorenyl] were prepared by allowing chloro-complexes [RuCl(η5-C9H7)(PPh3)L] to react with an excess of diazoalkane in ethanol. Complexes 1-3 reacted with ethylene CH2=CH2 (1 atm) and maleic anhydride [ma, CH=CHCO(O)CO] to afford η2-alkene complexes [Ru(η5-C9H7)(η2-CH2=CH2)(PPh3)L]BPh4 (4, 5) and [Ru(η5-C9H7){η2-CH=CHCO(O)CO}(PPh3)L]BPh4 (7). Further, complexes 1-3 underwent cycloaddition with acrylonitrile CH2=C(H)CN, giving 1H-pyrazoline derivatives [Ru(η5-C9H7){η1-N=C(CN)CH2C(Ar1Ar2)NH}(PPh3)L]BPh4 (6). Treatment of diazoalkane complexes 1-3 with acetylene CH≡CH under mild conditions (1 atm, room temperature) led to dipolar cycloaddition, affording 3H-pyrazole complexes [Ru(η5-C9H7)-{η1-N=NC(Ar1Ar2)CH=CH}(PPh3)L]BPh4 (8), whereas reaction with terminal alkynes RC≡CH (R = Ph, p-tolyl, But) gave vinylidene derivatives [Ru(η5-C9H7){=C=C(H)R}(PPh3)L]BPh4 (9). The latter reacted with nucleophiles such as amines and alcohols to give amino- and alkoxy-carbene derivatives [Ru(η5-C9H7){=C(NHPrn)(CH2Ph)}(PPh3)L]BPh4 (11) and [Ru(η5-C9H7){=C(CH3)(OEt)}(PPh3)L]BPh4 (10), respectively. In addition, complexes 9 reacted with phenylhydrazine to afford nitrile derivatives [Ru(η5-C9H7)(NC≡CH2R)(PPh3)L]BPh4 (12) and phenylamine, whereas the reaction with water led to hydrolysis of the alkyne and formation of carbonyl complexes [Ru(η5-C9H7)(CO)(PPh3)L]BPh4 (13). Lastly, treatment of vinylidene complexes 9 with the phosphines PPh3 and P(OMe)3 afforded alkenylphosphonium derivatives [Ru(η5-C9H7){C(H)=C(R)PPh3}(PPh3)L]BPh4 (14) and [Ru(η5-C9H7){C(R)=C(H)P(OMe)3}(PPh3)L]BPh4 (15), respectively. Compound [Ru(η5-C9H7){C(H)=C(H)PPh3}(PPh3)L]BPh4 (16) was also prepared. The complexes were characterised by spectroscopy (IR and NMR) and X-ray crystal structure determinations of [Ru(η5-C9H7){N2C(C12H8)}(PPh3){P(OEt)3}]BPh4 (3c), [Ru(η5-C9H7){=C=C(H)Ph}(PPh3){P(OEt)3}]BPh4 (9d) and [Ru(η5-C9H7){C(H)=C(Ph)PPh3}(PPh3){P(OEt)3}]BPh4 (14d).Diazoalkane complexes [Ru(eta(5)-C9H7)(N(2)CAr1Ar2)(PPh3)L]BPh4 (1-3) [L = PPh3, P(OMe)(3), P(OEt)(3); Ar1 = Ar2 = Ph; Ar1 = Ph, Ar2 = p-tolyl; Ar1Ar2 = C12H8 fluorenyl] were prepared by allowing chloro-complexes [RuCl(eta(5)-C9H7)(PPh3)L] to react with an excess of diazoalkane in ethanol. Complexes 1-3 reacted with ethylene CH2-CH2 (1 atm) and maleic anhydride [ma, CH-CHCO(O)CO] to afford eta(2)-alkene complexes [Ru(eta(5)-C9H7)(eta(2)-CH2=CH2)(PPh3)L]BPh4 (4, 5) and [Ru(eta(5)-C9H7){eta(2)-CH=CHCO(O)CO}(PPh3)L] BPh4 (7). Further, complexes 1-3 underwent cycloaddition with acrylonitrile CH2=C(H)CN, giving 1H-pyrazoline derivatives [Ru(eta(5)-C9H7){eta(1)-N=C(CN)CH2C(Ar1Ar2)NH}(PPh3)L]BPh4 (6). Treatment of diazoalkane complexes 1-3 with acetylene CH equivalent to CH under mild conditions (1 atm, room temperature) led to dipolar cycloaddition, affording 3H-pyrazole complexes [Ru(eta(5)-C9H7)-{eta(1)-N=NC(Ar1Ar2) CH=CH}(PPh3)L]BPh4 (8), whereas reaction with terminal alkynes RC equivalent to CH (R = Ph, p-tolyl, Bu-t) gave vinylidene derivatives [Ru(eta(5)-C9H7){=C=C(H) R}(PPh3)L]BPh4 (9). The latter reacted with nucleophiles such as amines and alcohols to give amino- and alkoxy-carbene derivatives [Ru(eta(5)-C9H7){=C(NHPrn)(CH2Ph)}(PPh3)L]BPh4 (11) and [Ru(eta(5)-C9H7){=C(CH3)(OEt)}(PPh3)L] BPh4 (10), respectively. In addition, complexes 9 reacted with phenylhydrazine to afford nitrile derivatives [Ru(eta(5)-C9H7)(N equivalent to CCH2R)(PPh3)L]BPh4 (12) and phenylamine, whereas the reaction with water led to hydrolysis of the alkyne and formation of carbonyl complexes [Ru(eta(5)-C9H7)(CO)(PPh3)L]BPh4 (13). Lastly, treatment of vinylidene complexes 9 with the phosphines PPh3 and P(OMe)(3) afforded alkenylphosphonium derivatives [Ru(eta(5)-C9H7){C(H) =C(R)PPh3}(PPh3)L]BPh4 (14) and [Ru(eta(5)-C9H7){C(R)=C(H) P(OMe)(3)}(PPh3)L]BPh4 (15), respectively. Compound [Ru(eta(5)-C9H7){C(H)=C(H)PPh3}(PPh3)L]BPh4 (16) was also prepared. The complexes were characterised by spectroscopy (IR and NMR) and X-ray crystal structure determinations of [Ru(eta(5)-C9H7){N2C(C12H8)}(PPh3){P(OEt)(3)}]BPh4 (3c), [Ru(eta(5)-C9H7){=C=C(H) Ph}(PPh3){P(OEt)(3)}] BPh4 (9d) and [Ru(eta(5)-C9H7){C(H)=C(Ph) PPh3}(PPh3){P(OEt)(3)}]BPh4 (14d)