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This article reflects on the Kinora replica project, an interdisciplinary collaboration between the Luxembourg Centre for Contemporary and Digital History (C2DH) and the Department of Engineering (DoE) of the University of Luxembourg. Combining historical inquiry with a hands-on and technical approach – involving the latest 3D modelling and desktop manufacturing engineering techniques – it provides insights into the process of making a working replica of the Kinora motion picture technology from the early 1900s.

The biblical book of Job is part of the traditional literature of antiquity but is also read as fictional literature in modern times. The figure of Job carries the prayer cry ‘Where is the Father?’ in his name. The story of Job and his passionate dialogues with friends revolve around the questions of why the righteous have to suffer and why God chose them to do so. Job only accepts an answer from God’s own mouth. But how is it possible to hear God’s voice? “Does our society allow communication with God?” (N. Luhmann). This book’s reflections on Job try to extend the thoughts of S. Kierkegaard, R. Girard, N. Kermani, M. Susman and M. Buber.

BACKGROUND Composite lipid emulsions containing soybean oil (30%), medium-chain triglycerides (30%), olive oil (25%), and fish oil (15%) (SMOF) are now widely used. OBJECTIVES We aimed to evaluate the tolerance, the efficiency, and the erythrocyte fatty acid (FA) profile for children on long-term home parenteral nutrition (HPN) receiving a composite fish oil-based emulsion (FOLE). METHODS At baseline, children (n = 46) with severe intestinal failure highly dependent on parenteral nutrition (PN) for ≥1 y were included in the study when they had received the composite FOLE for >6 mo. Out of this baseline group, only 25 children remained highly PN-dependent (SMOF1, n = 25) and could be assessed a second time, 2.4 y later (SMOF2, n = 25). An independent control group ("weaned off PN" group; n = 24) included children who had been weaned off PN for >2 y (median: 4 y). RBC-FA composition was established by GC-MS. Growth parameters, plasma citrulline, conjugated bilirubin, FA profiles, and the Holman ratio (20:3ω-9/20:4ω-6) were compared between groups. RESULTS No difference for growth parameters, citrulline, and bilirubin was observed between the SMOF groups after 2.4 y (0.2

IF 10.292; International audience; The hereditary spastic paraplegias are an expanding and heterogeneous group of disorders characterized by spasticity in the lower limbs. Plasma biomarkers are needed to guide the genetic testing of spastic paraplegia. Spastic paraplegia type 5 (SPG5) is an autosomal recessive spastic paraplegia due to mutations in CYP7B1, which encodes a cytochrome P450 7α-hydroxylase implicated in cholesterol and bile acids metabolism. We developed a method based on ultra-performance liquid chromatography electrospray tandem mass spectrometry to validate two plasma 25-hydroxycholesterol (25-OHC) and 27-hydroxycholesterol (27-OHC) as diagnostic biomarkers in a cohort of 21 patients with SPG5. For 14 patients, SPG5 was initially suspected on the basis of genetic analysis, and then confirmed by increased plasma 25-OHC, 27-OHC and their ratio to total cholesterol. For seven patients, the diagnosis was initially based on elevated plasma oxysterol levels and confirmed by the identification of two causal CYP7B1 mutations. The receiver operating characteristic curves analysis showed that 25-OHC, 27-OHC and their ratio to total cholesterol discriminated between SPG5 patients and healthy controls with 100% sensitivity and specificity. Taking advantage of the robustness of these plasma oxysterols, we then conducted a phase II therapeutic trial in 12 patients and tested whether candidate molecules (atorvastatin, chenodeoxycholic acid and resveratrol) can lower plasma oxysterols and improve bile acids profile. The trial consisted of a three-period, three-treatment crossover study and the six different sequences of three treatments were randomized. Using a linear mixed effect regression model with a random intercept, we observed that atorvastatin decreased moderately plasma 27-OHC (∼30%, P < 0.001) but did not change 27-OHC to total cholesterol ratio or 25-OHC levels. We also found an abnormal bile acids profile in SPG5 patients, with significantly decreased total serum bile acids associated with a relative decrease of ursodeoxycholic and lithocholic acids compared to deoxycholic acid. Treatment with chenodeoxycholic acid restored bile acids profile in SPG5 patients. Therefore, the combination of atorvastatin and chenodeoxycholic acid may be worth considering for the treatment of SPG5 patients but the neurological benefit of these metabolic interventions remains to be evaluated in phase III therapeutic trials using clinical, imaging and/or electrophysiological outcome measures with sufficient effect sizes. Overall, our study indicates that plasma 25-OHC and 27-OHC are robust diagnostic biomarkers of SPG5 and shall be used as first-line investigations in any patient with unexplained spastic paraplegia.

Georg Picht (1913–1982) gehort zu den Philosophen, die aus dem Umkreis von Martin Heidegger stammend, dessen Zugang zur Geschichte der Metaphysik weiterdachten. Er wurde 1964 auf den neu gegrundeten Lehrstuhl fur Religionsphilosophie an der Theologischen Fakultat in Heidelberg berufen, wo er bis zu seiner Emeritierung ein weites philosophiegeschichtliches und thematisches Spektrum abdeckte. Die Studienausgabe der Vorlesungen und Schriften von Georg Picht enthalt einen Band uber Nietzsche, der in dritter Auflage 2001 erschienen ist. Die erste Auflage erschien 1988. Der Band wird abgerundet durch einen Gedankenaustausch von Georg Picht und Enno Rudolph, dem Herausgeber dieses und anderer Bande der Edition von Pichts Vorlesungen und Schriften. Er hat sich u. a. auch um eine intensive Aneignung von Nietzsches Denken bemuht und gehort zu seinen ausdauernden und aufmerksamen Lesern. Sein komplexes Verhaltnis von Nahe und Distanz zu Heidegger macht eine knappe Ubersicht nicht leicht (vgl. 1989, 279 und 181). Gleichwohl soll ein solcher Uberblick – mit gewissen Vereinfachungen – hier gewagt werden. Besonders erwahnenswert ist die Tatsache, dass der ‚gottlose‘ Nietzsche von Picht zum Prufstein einer zeitgemasen Theologie gemacht wird, die sich vom Schatten des Platonismus und der Absicht zur Apologie verabschiedet hat. Damit gehort Georg Picht zu jenen Denkern innerhalb der protestantischen Theologie, die von Nietzsche fur ihr eigenes religionsphilosophisches Selbstverstandnis maximal profitieren, ohne voreilige Abwehrreflexe gegen dessen „Fluch auf das Christenthum“ (Untertitel von Der Antichrist). Philosophie braucht nicht Stutzgruppen von Gleichgesinnten, sondern freie Lust am Denken, wohin es auch fuhren mag.

Bile acid (BA) secretion and circulation in chronic pancreatitis (CP) patients with exocrine pancreatic insufficiency (EPI) were investigated by simultaneously measuring postprandial levels of individual BAs in duodenal contents and blood plasma using LC-MS/MS. CP patients and healthy volunteers (HVs) were intubated with gastric and duodenal tubes prior to the administration of a test meal and continuous aspiration of duodenal contents. Pancreatic lipase outputs in CP patients were very low (0.7 ± 0.2 mg) versus HVs (116.7 ± 68.1 mg; P < 0.005), thus confirming the severity of EPI. Duodenal BA outputs were reduced in CP patients (1.00 ± 0.89 mmol; 0.47 ± 0.42 g) versus HVs (5.52 ± 4.53 mmol; 2.62 ± 2.14 g; P < 0.15). Primary to secondary BA ratio was considerably higher in CP patients (38.09 ± 48.1) than HVs (4.15 ± 2.37; P < 0.15), indicating an impaired transformation of BAs by gut microbiota. BA concentrations were found below the critical micellar concentration in CP patients, while a high BA concentration peak corresponding to gallbladder emptying was evidenced in HVs. Conversely, BA plasma concentration was increased in CP patients versus HVs suggesting a cholangiohepatic shunt of BA secretion. Alterations of BA circulation and levels may result from the main biliary duct stenosis observed in these CP patients and may aggravate the consequences of EPI on lipid malabsorption.

Multivariate data methods have been applied in analysis of parameters derived from patients with metabolic syndrome undergoing a remedial regime. In an example involving parameters derived from the fatty acid composition of serum lipids multivariate modeling is challenged to identify potential biomarkers for prediction during the intervention. Multivariate methods also reveal useful applications to monitor compliance to the prescribed exercise and diet regime, a critical feature in a lifestyle intervention conducted over a long time period.

Background Results of finite element (FE) analyses can give insight into musculoskeletal diseases if physiological boundary conditions, which include the muscle forces during specific activities of daily life, are considered in the FE modelling. So far, many simplifications of the boundary conditions are currently made. This study presents an approach for FE modelling of the lower limb for which muscle forces were included. Methods The stance phase of normal gait was simulated. Muscle forces were calculated using a musculoskeletal rigid body (RB) model of the human body, and were subsequently applied to a FE model of the lower limb. It was shown that the inertial forces are negligible during the stance phase of normal gait. The contact surfaces between the parts within the knee were modelled as bonded. Weak springs were attached to the distal tibia for numerical reasons. Results Hip joint reaction forces from the RB model and those from the FE model were similar in magnitude with relative differences less than 16%. The forces of the weak spring were negligible compared to the applied muscle forces. The maximal strain was 0.23% in the proximal region of the femoral diaphysis and 1.7% in the contact zone between the tibia and the fibula. Conclusions The presented approach based on FE modelling by including muscle forces from inverse dynamic analysis of musculoskeletal RB model can be used to perform analyses of the lower limb with very realistic boundary conditions. In the present form, this model can be used to better understand the loading, stresses and strains of bones in the knee area and hence to analyse osteotomy fixation devices.

Ascorbate mobilizes iron from equine spleen ferritin by two separate processes. Ascorbate alone mobilizes ferritin iron with an apparent Km (ascorbate) ≈ 1.5 mM. Labile iron > 2 μM, complexed with citrate (10 mM), synergises ascorbate-dependent iron mobilization by decreasing the apparent Km (ascorbate) to ≈ 270 μM and raising maximal mobilization rate by ≈ 5-fold. Catalase reduces the apparent Km(ascorbate) for both ascorbate and ascorbate + iron dependent mobilization by ≈ 80%. Iron mobilization by ascorbate alone has a higher activation energy (Ea = 45.0 ± 5.5 kJ/mole) than when mediated by ascorbate with labile iron (10 μM) (Ea = 13.7 ± 2.2 kJ/mole); also mobilization by iron-ascorbate has a three-fold higher pH sensitivity (pH range 6.0–8.0) than with ascorbate alone. Hydrogen peroxide inhibits ascorbate's iron mobilizing action. EPR and autochemiluminescence studies show that ascorbate and labile iron within ferritin enhances radical formation, whereas ascorbate alone produces negligible radicals. These findings suggest that iron catalysed single electron transfer reactions from ascorbate, involving ascorbate or superoxide and possibly ferroxidase tyrosine radicals, accelerate iron mobilization from the ferroxidase centre more than EPR silent, bi-dentate two-electron transfers. These differing modes of electron transference from ascorbate mirror the known mono and bidentate oxidation reactions of dioxygen and hydrogen peroxide with di-ferrous iron at the ferroxidase centre. This study implies that labile iron, at physiological pH, complexed with citrate, synergises iron mobilization from ferritin by ascorbate (50–4000 μM). This autocatalytic process can exacerbate oxidative stress in ferritin-containing inflamed tissue.

Ist Pantheismus eine verwerfliche Häresie, die zu Atheismus und Materialismus führt? Oder die universelle Religion der Zukunft? Beide Fragen lassen sich deshalb nicht bündig beantworten, weil es »den« Pantheismus nicht gibt. Es gibt zahlreiche Spielarten des Pantheismus. Eine Spurensuche findet sie in den Religionen nach der Aufklärung, insbesondere bei einer Reihe von europäischen und außereuropäischen Philosophen (Tagore), die den Übergang von Kants Kritizismus zu einer neuen Vision auf das Eine und Ganze wagen. Ein dynamischer Neospinozismus (Lessing, Herder) inspiriert mehr als eine Generation von Denkern und Dichtern. Um kontroverstheologische Abgrenzungen und weltanschauliche, insbesondere naturalistische Vereinnahmungen zu verhindern, wird ein weiter und offener Begriff von »Pantheismen« untersucht (Herder, Schleiermacher). Am Beispiel von Hegels Ausführungen zum unglücklichen Bewusstsein wird eine spekulative Variante von Pantheismus dargestellt. Der Übergang vom Pantheismus zum Atheismus (Feuerbach, Bruno Bauer) ist möglich, aber nicht zwingend. Einige Pantheisten verknüpfen die autonome (oder »reine«) Ethik mit heteronomen Elementen der Abhängigkeit der Menschen vom Einen und Ganzen. Für eine monistische Deutung der Ethik (Schopenhauer) wird die Verschiedenheit unter den Individuen unwichtig. Auch das Interesse von Hegel und Schopenhauer für den Mesmerismus bezeugt eine Annäherung der »Aufklärung über die Aufklärung« an Elemente einer liberalen Weltfrömmigkeit. Der Mesmerismus wird von Emerson erweitert zum Gleichnis des Einen und Allen.