‘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

SERS spectroscopy as a tool for the study of thiopurine drug pharmacokinetics in a model of human B leukemia cells

: The thiopurine drugs are immunomodulatory antimetabolites that are characterized by dose-dependent adverse effects such as myelosuppression and hepatotoxicity, often related to inter-individual differences, involving the activity of important enzymes at the basis of their biotransformation, such as thiopurine S-methyltransferase (TPMT). Surface Enhanced Raman Scattering (SERS) spectroscopy is emerging as a bioanalytical tool and represents a valid alternative in terms of affordable costs, shorter analysis time and easier sample preparation in comparison to the most employed methods for pharmacokinetic analysis of drugs. The aim of this study is to investigate mercaptopurine and thioguanine pharmacokinetics by SERS in cell lysates of a B-lymphoblastoid cell line (NALM-6), that did (TPMT*1) or did not (MOCK) overexpress the wild-type form of TPMT as an in vitro cellular lymphocyte model to discriminate between cells with different levels of TPMT activity on the base of the amount of thioguanosine nucleotides (TGN) metabolites formed. SERS analysis of the cell lysates was carried out using SERS substrates constituted by Ag nanoparticles deposited on paper and parallel samples were used for quantification of thiopurine nucleotides with liquid chromatography-tandem mass-spectrometry (LC-MS/MS). A direct SERS detection method has been set up that could be a tool to study thiopurine drug pharmacokinetics in in vitro cellular models to qualitatively discriminate between cells that do and do not overexpress the TPMT enzyme, as an alternative to other more laborious techniques. Results underlined decreased levels of TGN and increased levels of methylated metabolites when TPMT was over expressed, both after mercaptopurine and thioguanine treatments. A strong positive correlation (Spearman's rank correlation coefficient rho = 0.96) exists between absolute quantification of TGMP (pmol/1x106 cells), obtained by LC-MS/MS, and SERS signal (intensity of TGN at 915 cm-1). In future studies, we aim to apply this method to investigate TPMT activity in patients' leukocytes

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