La sculpture comme lieu

Ce travail vise à analyser plus en profondeur le rapport entre la sculpture et le lieu. Bien que la spécificité du lieu soit un aspect important de l'analyse, il s'agira en premier lieu de définir ces deux concepts pour mieux en comprendre la corrélation. En effet, qu'est-ce que le lieu ? Qu'est-ce que la sculpture ? Quel est le rapport entre les deux ? Martin Heidegger en donne un point de départ dans son essaie L'art et l'espace. En pensant le lieu comme un lieu de rencontre qui crée une proximité entre les choses et les hommes, il semble également pertinent d'examiner l'œuvre sculpturale par rapport à sa capacité à établir une proximité avec le spectateur. Nous avons choisi de fonder notre réflexion sur une analyse détaillée de deux œuvres sculpturales qui nous semblent particulièrement riches et pertinentes pour interroger ce rapport sculpture/lieu. La première est Pulitzer Piece de Richard Serra et la seconde House de Rachel Whiteread. Toutes deux partent de la spécificité du lieu et en font leur "échelle" architecturale. L'étude de ces deux œuvres permet par ailleurs d'élargir le champ d'analyse et d'éviter un point de vue unilatéral

Investigations on nutritional characteristics of microalgae with emphasis on ruminants

The main objective of the present thesis was to systematically determine nutritional characteristics of microalgae and evaluate the suitability of microalgae as feedstuffs, particularly for ruminants. The experiments comprised a comprehensive characterisation of microalgae nutrient profiles with chemical-analytical methods and the determination of extent and dynamics of nutrient utilization using in vitro methods. In order to generate a comprehensive database on nutrient composition of microalgae, 16 commercial microalgae biomasses of four genera (Arthrospira, Chlorella, Nannochloropsis, and Phaeodactylum) were analysed utilizing established methods for food and feed evaluation (Manuscript 1). These investigations included determination of the in vitro crude protein (CP) digestibility for pigs. Nutrient analyses showed a considerable variation particularly in concentrations of proximate nutrients, minerals, and fatty acids, both among and within genera. This variation presumably resulted from varying cultivation conditions and it was concluded that general mean values are not appropriate to characterize microalgae in terms nutrient composition. Manuscript 2 aimed to determine characteristics of the nutritional value of microalgae for ruminants utilizing different in vitro methods. The commercial biomasses included in Manuscript 1 were investigated using the Hohenheim Gas Test method. The investigations comprised the determination of several ruminal fermentation characteristics, of the energy value, and of the protein value. A three-step enzymatic in vitro system was used to estimate intestinal digestibility of ruminally undegraded CP (IDP). Ruminal fermentation of the investigated microalgae biomasses was overall low, which was indicated by an overall low level of production of gas and volatile fatty acids, and a low ruminal CP degradation. As a result of low ruminal fermentation, microalgae biomasses were characterized by high concentrations of ruminally undegradable CP (RUP; 386, 399, 315, and 263 g RUP/kg DM at passage rate of 8 %/h for Arthrospira, Chlorella, Nannochloropsis, and Phaeodactylum, respectively). Thus, microalgae appear to be potential alternative protein sources for high performing animals. However, this was contradicted by low IDP, which was determined for microalgae in the present thesis for the first time (mean values for Arthrospira, Chlorella, Nannochloropsis, and Phaeodactylum were 27, 43, 43, and 40 % of RUP respectively). The variation observed in nutrient profiles was reflected in several nutritional characteristics. A common objective of Manuscript 1 and Manuscript 2 was to investigate whether cell disruption affects nutritional characteristics of microalgae. In Manuscript 1, effects of cell disruption on in vitro CP digestibility for pigs were investigated and in Manuscript 2 several in vitro methods were utilized to investigate effects of cell disruption on the nutritional value of microalgae for ruminants. Mechanical cell disruption with a ball mill enhanced in vitro CP digestibility and ruminal fermentation in most of the samples, presumably by the destruction of cells and hence an increase in nutrient accessibility. Nevertheless, concerning the protein value of microalgae in ruminants, application of mechanical cell disruption cannot not be recommended because it decreased RUP but did not increase IDP so that intestinal digestible RUP was overall decreased by cell disruption. The aim of the third manuscript was to investigate the effects of variable cultivation conditions on nutrient composition and nutritional characteristics for ruminants of the microalgae Chlorella vulgaris. Chlorella vulgaris was cultivated under varying conditions (saturation, nitrogen and CO2 depletion, outdoor cultivation). The obtained biomasses were analysed for their nutrient composition and their nutritional value for ruminants using different in vitro methods. Both, nutrient composition and characteristics of the nutritional value for ruminants were affected by the cultivation process. Nutrient deficient conditions had rather adverse effects in terms of digestibility, protein value, and nutrient productivity. It can be concluded that microalgae have potential as alternative protein source for ruminants. Nevertheless, this potential is contradicted by low IDP, but the findings obtained herein have to be verified in future studies. Furthermore, the results of the present thesis show that nutrient composition and ruminal fermentation characteristics of microalgae vary considerably between and in many cases even within microalgae genera. Thus, to the extent possible, it should be strived for a standardisation of cultivation conditions, in order allow better predictions of nutritional characteristics of microalgae.Das Hauptziel der vorliegenden Arbeit war es, systematisch Futterwerteigenschaften von Mikroalgen zu untersuchen und ihre Eignung als Futtermittel, insbesondere für Wiederkäuer, zu bewerten. Die Untersuchungen beinhalteten eine umfassende Charakterisierung der Nährstoffprofile von Mikroalgen mit Labormethoden, sowie die Bestimmung von Ausmaß und Dynamik der Nährstoffverwertung mit in vitro Methoden. Um eine umfassende Datengrundlage zu den Nährstoffprofilen von Mikroalgen zu schaffen, wurden 16 kommerzielle Mikroalgenbiomassen von vier Gattungen (Arthrospira, Chlorella, Nannochloropsis und Phaeodactylum) mit etablierten Methoden der Lebens- und Futtermittelbewertung untersucht (Manuskript 1). Diese Untersuchungen beinhalteten die Bestimmung der Verdaulichkeit des Rohproteins (XP) von Mikroalgen für Schweine. Die Nährstoffanalytik zeigte sowohl zwischen als auch innerhalb der Gattungen eine erhebliche Variation, insbesondere in den Konzentrationen von Rohnährstoffen, Mineralstoffen und Fettsäuren. Diese Variation resultierte vermutlich aus unterschiedlichen Kultivierungsbedingungen und es wurde geschlussfolgert, dass allgemeingültige Mittelwerte ungeeignet sind, um Mikroalgen hinsichtlich ihrer Nährstoffzusammensetzung zu charakterisieren. Das Ziel der Untersuchungen für Manuskript 2 war es, Futterwerteigenschaften von Mikroalgen für Wiederkäuer mit verschiedenen in vitro Methoden zu bestimmen. Die kommerziellen Biomassen aus Manuskript 1 wurden mit der Methode des Hohenheimer Futterwerttests untersucht. Die Untersuchungen umfassten die Bestimmung verschiedener Charakteristika der ruminalen Fermentation, des Energiewertes und des Proteinwertes. Ein dreistufiges, enzymatisches in vitro System wurde verwendetet, um die intestinale Verdaulichkeit des ruminal nicht abbaubaren XP (IDP) zu ermitteln. Die ruminale Fermentation der untersuchten Mikroalgen war gering, was anhand des generell niedrigen Niveaus der Produktion von Gas und flüchtigen Fettsäuren, sowie dem niedrigen ruminalen XP-Abbau deutlich wurde. Als Folge des niedrigen ruminalen XP-Abbaus wurden die Mikroalgenbiomassen durch hohe Konzentrationen an ruminal nicht abbaubaren XP (UDP) geprägt (386, 399, 315 und 263 g UDP/kg Trockenmasse bei einer Passagerate von 8 %/h für Arthrospira, Chlorella, Nannochloropsis und Phaeodactylum). Demnach scheinen Mikroalgen als alternative Proteinquelle Potential zu haben, insbesondere für Hochleistungstiere. Allerdings ist dieses Potential durch die geringe IDP, die im Rahmen der vorliegenden Arbeit das erste Mal für Mikroalgen ermittelt wurde, möglicherweise stark eingeschränkt (Mittelwerte für Arthrospira, Chlorella, Nannochloropsis und Phaeodactylum: 27, 43, 43 und 40 % des UDP). Die Variation, die bei den Nährstoffprofilen beobachtet wurde, spiegelte sich auch in verschiedenen Futterwerteigenschaften für Wiederkäuer wider. Ein gemeinsames Ziel von Manuskript 1 und Manuskript 2 war es, zu untersuchen ob ein Zellwandaufschluss die Futterwerteigenschaften von Mikroalgen beeinflusst. In Manuskript 1 wurde der Effekt eines Zellwandschlusses auf die in vitro XP-Verdaulichkeit von Mikroalgen beim Schwein untersucht. In Manuskript 2 wurden verschiedene in vitro Methoden genutzt um die Effekte eines Zellwandaufschlusses auf Futterwerteigenschaften für Wiederkäuer zu untersuchen. Ein mechanischer Zellwandaufschluss mit einer Rührwerkskugelmühle erhöhte bei den meisten Proben die in vitro XP-Verdaulichkeit und die ruminale Fermentation, was wahrscheinlich auf die Zerstörung der Zellwände und die daraus resultierende Erhöhung der Nährstoffverfügbarkeit zurückzuführen war. Allerdings führte dies zu einer geringeren Konzentration an UDP, wobei die IDP nicht zunahm, sodass die Menge an intestinal verdaulichem UDP generell sank. Daher ist die Anwendung eines mechanischen Zellwandaufschlusses von Mikroalgen hinsichtlich ihres Proteinwertes für Wiederkäuer als ungünstig zu bewerten und kann nicht empfohlen werden. Das Ziel des dritten Manuskripts war es, die Effekte von verschiedenen Kultivierungsbedingungen auf die Nährstoffzusammensetzung und die Futterwerteigenschaften für Wiederkäuer bei der Mikroalge Chlorella vulgaris zu untersuchen. Chlorella vulgaris wurde bei variierenden Bedingungen (Nährstoffsättigung, Stickstoff- und CO2-Limitierung, Freiland) kultiviert. Die gewonnenen Biomassen wurden hinsichtlich ihrer Nährstoffzusammensetzung und ihrer Futterwerteigenschaften für Wiederkäuer mit in vitro Methoden untersucht. Sowohl die Nährstoffzusammensetzung als auch Futterwerteigenschaften für Wiederkäuer wurden durch den Kultivierungsprozess beeinflusst. Hinsichtlich der Verdaulichkeit und des Proteinwertes, sowie hinsichtlich der Nährstoffproduktivität hatte eine Nährstofflimitierung eher ungünstige Effekte. Zusammenfassend lässt sich sagen, dass Mikroalgen Potential als alternative Proteinquelle für Wiederkäuer haben. Allerdings ist dieses Potential durch die niedrige IDP möglicherweise stark einschränkt. Daher sollten die Ergebnisse der vorliegenden Arbeit in zukünftigen Studien verifiziert werden. Außerdem zeigen die Ergebnisse dieser Arbeit, dass sowohl die Nährstoffzusammensetzung, als auch die Futterwerteigenschaften von Mikroalgen für Wiederkäuer einer großen Variation unterliegen. Die gilt nicht nur zwischen den untersuchten Mikroalgengattungen, sondern in vielen Fällen auch innerhalb einer Gattung. Daher sollte, soweit möglich, eine Standardisierung der Kultivierungsbedingungen angestrebt werden, um eine bessere Vorhersagbarkeit von Futterwerteigenschaften für Mikroalgen zu ermöglichen

Um novo método para simular o estado hidrológico do solo em condições naturais

Micro, macro and mesofauna in the soil often respond to fluctuating environmental conditions, resulting in changes of abundance and community structure. Effects of changing soil parameters are normally determined with samples taken in the field and brought to the laboratory, i.e. where natural environmental conditions may not apply. We devised a method (STAFD – soil tubes for artificial flood and drought), which simulates the hydrological state of soil in situ using implanted cores. Control tubes were compared with treatment tubes in which floods of 15, 30, 60 and 90 days, and droughts of 60, 90 and 120 days were simulated in the field. Flooding and drought were found to reduce number of individuals in all soil faunal groups, but the response to drought was slower and not in proportion to the expected decrease of the water content. The results of the simulated floods in particular show the value of the STAFD method for the investigation of such extreme events in natural habitats.As micro, macro e mesofaunas no solo respondem frequentemente à variação das condições ambientais, o que resulta em alterações na abundância e na estrutura da comunidade. Os efeitos das alterações nos parâmetros do solo são normalmente determinados com amostras recolhidas no campo e trazidas ao laboratório, ou seja, onde as condições ambientais naturais podem não ser aplicáveis. Criamos um método (STAFD – tubos de amostra de solo para inundações e secas artificiais), que simula o estado hidrológico do solo in situ com núcleos implantados. As amostras de controle foram comparadas com amostras de tratamentos em que foram simuladas inundações de 15, 30, 60 e 90 dias e secas de 60, 90 e 120 dias no campo. Verificou-se que as inundações e a seca reduziram a quantidade de individuos em todos os grupos de fauna de solo, mas a resposta à seca foi mais lenta e não proporcional à redução prevista no teor de água. Os resultados das inundações simuladas demonstram, em especial, o valor do método STAFD para a investigação desse tipo de eventos extremos nos habitats naturais

Variation in colorectal cancer treatment and outcomes in Scotland:real world evidence from national linked administrative health data

Background: Colorectal cancer (CRC) is the fourth most common type of cancer in the United Kingdom and the second leading cause of cancer death. Despite improvements in CRC survival over time, Scotland lags behind its UK and European counterparts. In this study, we carry out an exploratory analysis which aims to provide contemporary, population level evidence on CRC treatment and survival in Scotland. Methods: We conducted a retrospective population-based analysis of adults with incident CRC registered on the Scottish Cancer Registry (Scottish Morbidity Record 06 (SMR06)) between January 2006 and December 2018. The CRC cohort was linked to hospital inpatient (SMR01) and National Records of Scotland (NRS) deaths records allowing a description of their demographic, diagnostic and treatment characteristics. Cox proportional hazards regression models were used to explore the demographic and clinical factors associated with all-cause mortality and CRC specific mortality after adjusting for patient and tumour characteristics among people identified as early-stage and treated with surgery. Results: Overall, 32,691 (73%) and 12,184 (27%) patients had a diagnosis of colon and rectal cancer respectively, of whom 55% and 53% were early-stage and treated with surgery. Five year overall survival (CRC specific survival) within this cohort was 72% (82%) and 76% (84%) for patients with colon and rectal cancer respectively. Cox proportional hazards models revealed significant variation in mortality by sex, area-based deprivation and geographic location.Conclusions: In a Scottish population of patients with early-stage CRC treated with surgery, there was significant variation in risk of death, even after accounting for clinical factors and patient characteristics.<br/

A New Type of Metal Recognition by Human T Cells: Contact Residues for Peptide-independent Bridging of T Cell Receptor and Major Histocompatibility Complex by Nickel

In spite of high frequencies of metal allergies, the structural basis for major histocompatibility complex (MHC)-restricted metal recognition is among the unanswered questions in the field of T cell activation. For the human T cell clone SE9, we have identified potential Ni contact sites in the T cell receptor (TCR) and the restricting human histocompatibility leukocyte antigen (HLA)-DR structure. The specificity of this HLA-DR–promiscuous VA22/VB17+ TCR is primarily harbored in its α chain. Ni reactivity is neither dependent on protein processing in antigen-presenting cells nor affected by the nature of HLA-DR–associated peptides. However, SE9 activation by Ni crucially depends on Tyr29 in CDR1α, an N-nucleotide–encoded Tyr94 in CDR3α, and a conserved His81 in the HLA-DR β chain. These data indicate that labile, nonactivating complexes between the SE9 TCR and most HLA-DR/peptide conjugates might supply sterically optimized coordination sites for Ni ions, three of which were identified in this study. In such complexes Ni may effectively bridge the TCR α chain to His81 of most DR molecules. Thus, in analogy to superantigens, Ni may directly link TCR and MHC in a peptide-independent manner. However, unlike superantigens, Ni requires idiotypic, i.e., CDR3α-determined TCR amino acids. This new type of TCR–MHC linkage might explain the high frequency of Ni-reactive T cells in the human population

Correction:Prevalence and Cardiovascular Associations of Diabetic Retinopathy and Maculopathy: Results from the Gutenberg Health Study

Diabetic retinopathy (DR) is the leading cause of blindness in people of working age. The purpose of this paper is to report the prevalence and cardiovascular associations of diabetic retinopathy and maculopathy (DMac) in Germany.The Gutenberg Health Study (GHS) is a population-based study with 15,010 participants aged between 35 at 74 years from the city of Mainz and the district of Mainz-Bingen. We determined the weighted prevalence of DR and DMac by assessing fundus photographs of persons with diabetes from the GHS data base. Diabetes was defined as HbA1c ≥ 6.5%, known diagnosis diabetes mellitus or known diabetes medication. Furthermore, we analysed the association between DR and cardiovascular risk factors and diseases.Overall, 7.5% (1,124/15,010) of the GHS cohort had diabetes. Of these, 27.7% were unaware of their disease and thus were newly diagnosed by their participation in the GHS. The prevalence of DR and DMac was 21.7% and 2.3%, respectively among patients with diabetes. Vision-threatening disease was present in 5% of the diabetic cohort. In the multivariable analysis DR (all types) was associated with age (Odds Ratio [95% confidence interval]: 0.97 [0.955-0.992]; p = 0.006) arterial hypertension (1.90 [1.190-3.044]; p = 0.0072) and vision-threatening DR with obesity (3.29 [1.504-7.206]; p = 0.0029). DR (all stages) and vision-threatening DR were associated with duration of diabetes (1.09 [1.068-1.114]; p<0.0001 and 1.18 [1.137-1.222]; p<0.0001, respectively).Our calculations suggest that approximately 142 000 persons aged between 35 and 74 years have vision threatening diabetic retinal disease in Germany [corrected].Prevalence of DR was lower in the GHS compared to East-Asian studies. Associations were found with age, arterial hypertension, obesity, and duration of diabetes mellitus

Reactive oxygen species produced by myeloid cells in psoriasis as a potential biofactor contributing to the development of vascular inflammation.

Psoriasis is an immune-mediated inflammatory skin disease driven by interleukin-17A (IL-17A) and associated with cardiovascular dysfunction. We used a severe psoriasis mouse model of keratinocyte IL-17A overexpression (K14-IL-17Aind/+ , IL-17Aind/+ control mice) to investigate the activity of neutrophils and a potential cellular interconnection between skin and vasculature. Levels of dermal reactive oxygen species (ROS) and their release by neutrophils were measured by lucigenin-/luminol-based assays, respectively. Quantitative RT-PCR determined neutrophilic activity and inflammation-related markers in skin and aorta. To track skin-derived immune cells, we used PhAM-K14-IL-17Aind/+ mice allowing us to mark all cells in the skin by photoconversion of a fluorescent protein to analyze their migration into spleen, aorta, and lymph nodes by flow cytometry. Compared to controls, K14-IL-17Aind/+ mice exhibited elevated ROS levels in the skin and a higher neutrophilic oxidative burst accompanied by the upregulation of several activation markers. In line with these results psoriatic mice displayed elevated expression of genes involved in neutrophil migration (e.g., Cxcl2 and S100a9) in skin and aorta. However, no direct immune cell migration from the psoriatic skin into the aortic vessel wall was observed. Neutrophils of psoriatic mice showed an activated phenotype, but no direct cellular migration from the skin to the vasculature was observed. This suggests that highly active vasculature-invading neutrophils must originate directly from the bone marrow. Hence, the skin-vasculature crosstalk in psoriasis is most likely based on the systemic effects of the autoimmune skin disease, emphasizing the importance of a systemic therapeutic approach for psoriasis patients

Respostas e adaptações de comunidades de colêmbolos (Hexapoda: Collembola) a condições de inundação e hipoxia

Standard ecological methods (pitfall traps, trunk eclectors and soil cores) were used to evaluate collembolan community responses to different flooding intensities. Three sites of a floodplain habitat near Mainz, Germany, with different flooding regimes were investigated. The structures of collembolan communities are markedly different depending on flooding intensity. Sites more affected by flooding are dominated by hygrophilic and hygrotolerant species, whereas the hardwood floodplain is dominated by mesophilic species. The survival strategies of the hygrophilic and hygrotolerant species include egg diapause and passive drifting. The physiological adaptations to hypoxic conditions of several collembolan species were analyzed using a microcalorimeter. The activities were tested under normoxic and hypoxic/anoxic conditions as well as during post-hypoxic recovery. Lactate was increased after hypoxic intervals in the species studied, suggesting that, in addition to a massive decrease in metabolic rate, a modest glycolytic activity may be involved in the tolerance to hypoxia.Foram utilizados os métodos ecológicos padrão (armadilhas "pitfall", armadilhas de tronco e amostras de solo) para avaliar as respostas de comunidade de colêmbolos a diferentes intensidades de inundação. Foram investigados três locais de um habitat de leitos de inundação perto de Mainz, Alemanha, com diferentes regimes de inundação. As estruturas das comunidades de colêmbolos foram nitidamente diferentes conforme a intensidade das inundações. Nos locais mais afetados por inundações, as espécies higrofílicas e higrotolerantes dominaram, ao passo que as espécies mesofílicas foram dominantes nos locais de leitos de inundação com angiospermas. As estratégias de sobrevivência das espécies higrofílicas e higrotolerantes incluem a diapausa dos ovos e o deslocamento passivo. Foi testada a adaptação fisiológica a condições hipóxicas de espécies selecionadas de colêmbolos através de análises por microcalorimetria. A atividade das espécies foi testada em condições normóxicas e hipóxicas/anóxicas e durante a recuperação pós-hipoxia. Verificou-se que o lactato aumentava após condições hipóxicas nas espécies avaliadas, o que sugere que, além de um decréscimo massivo na atividade metabólica, deve haver também certa atividade glicolítica associada à tolerância à hipoxia

Machine-learning-aided prediction of brain metastases development in non-small-cell lung cancers

Purpose Non–small-cell lung cancer (NSCLC) shows a high incidence of brain metastases (BM). Early detection is crucial to improve clinical prospects. We trained and validated classifier models to identify patients with a high risk of developing BM, as they could potentially benefit from surveillance brain MRI. Methods Consecutive patients with an initial diagnosis of NSCLC from January 2011 to April 2019 and an in-house chest-CT scan (staging) were retrospectively recruited at a German lung cancer center. Brain imaging was performed at initial diagnosis and in case of neurological symptoms (follow-up). Subjects lost to follow-up or still alive without BM at the data cut-off point (12/2020) were excluded. Covariates included clinical and/or 3D-radiomics-features of the primary tumor from staging chest-CT. Four machine learning models for prediction (80/20 training) were compared. Gini Importance and SHAP were used as measures of importance; sensitivity, specificity, area under the precision-recall curve, and Matthew's Correlation Coefficient as evaluation metrics. Results Three hundred and ninety-five patients compromised the clinical cohort. Predictive models based on clinical features offered the best performance (tuned to maximize recall: sensitivity∼70%, specificity∼60%). Radiomics features failed to provide sufficient information, likely due to the heterogeneity of imaging data. Adenocarcinoma histology, lymph node invasion, and histological tumor grade were positively correlated with the prediction of BM, age, and squamous cell carcinoma histology were negatively correlated. A subgroup discovery analysis identified 2 candidate patient subpopulations appearing to present a higher risk of BM (female patients + adenocarcinoma histology, adenocarcinoma patients + no other distant metastases). Conclusion Analysis of the importance of input features suggests that the models are learning the relevant relationships between clinical features/development of BM. A higher number of samples is to be prioritized to improve performance. Employed prospectively at initial diagnosis, such models can help select high-risk subgroups for surveillance brain MRI