Analyzing Infrastructures in the Anthropocene

This contribution takes the multiple ecological crises as the background to connect discourses on sustainability and infrastructures. It discusses the preservation, development, or disorder of infrastructures by different actors and practices in the context of diverse imaginaries of sustainability. When infrastructures are addressed and scrutinized against different visions of the future, their order-forming elements, dysfunctionalities, and transformation potentials come to the fore. The question of which decisions, translations, and norms are inscribed in infrastructures is of particular importance in the discourses on ecology. Moreover, focusing on the planetary dimensions of the ecological crisis adds particular complexity to the infrastructural analysis. An ecological perspective fundamentally challenges the view of infrastructure, as traditional concepts are no longer able to contribute to necessary planetary solutions. Since struggles for the futures of sustainability are struggles for the modernization and transformation of, as well as control over and through (material, immaterial, planetary), infrastructures, we argue that infrastructures will and should receive special attention in the social sciences and humanities in the future

Quantitative Stain-free and Continuous Multimodal Monitoring of Wound Healing in vitro with Digital Holographic Microscopy

Impaired epithelial wound healing has significant pathophysiological implications in several conditions including gastrointestinal ulcers, anastomotic leakage and venous or diabetic skin ulcers. Promising drug candidates for accelerating wound closure are commonly evaluated in in vitro wound assays. However, staining procedures and discontinuous monitoring are major drawbacks hampering accurate assessment of wound assays. We therefore investigated digital holographic microscopy (DHM) to appropriately monitor wound healing in vitro and secondly, to provide multimodal quantitative information on morphological and functional cell alterations as well as on motility changes upon cytokine stimulation. Wound closure as reflected by proliferation and migration of Caco-2 cells in wound healing assays was studied and assessed in time-lapse series for 40 h in the presence of stimulating epidermal growth factor (EGF) and inhibiting mitomycin c. Therefore, digital holograms were recorded continuously every thirty minutes. Morphological changes including cell thickness, dry mass and tissue density were analyzed by data from quantitative digital holographic phase microscopy. Stimulation of Caco-2 cells with EGF or mitomycin c resulted in significant morphological changes during wound healing compared to control cells. In conclusion, DHM allows accurate, stain-free and continuous multimodal quantitative monitoring of wound healing in vitro and could be a promising new technique for assessment of wound healing

Samarium(II) folding cascades involving hydrogen atom transfer for the synthesis of complex polycycles

The expedient assembly of complex, natural product-like small molecules can deliver new chemical entities with the potential to interact with biological systems and inspire the development of new drugs and probes for biology. Diversity-oriented synthesis is a particularly attractive strategy for the delivery of complex molecules in which the 3-dimensional architecture varies across the collection. Here we describe a folding cascade approach to complex polycyclic systems bearing multiple stereocentres mediated by reductive single electron transfer (SET) from SmI2. Simple, linear substrates undergo three different folding pathways triggered by reductive SET. Two of the radical cascade pathways involve the activation and functionalization of otherwise inert secondary alkyl and benzylic groups by 1,5-hydrogen atom transfer (HAT). Combination of SmI2, a privileged reagent for cascade reactions, and 1,5-HAT can lead to complexity-generating radical sequences that unlock access to diverse structures not readily accessible by other means

Differentiation Therapy Targeting the β-Catenin/CBP Interaction in Pancreatic Cancer.

BACKGROUND:Although canonical Wnt signaling is known to promote tumorigenesis in pancreatic ductal adenocarcinoma (PDAC), a cancer driven principally by mutant K-Ras, the detailed molecular mechanisms by which the Wnt effector β-catenin regulates such tumorigenesis are largely unknown. We have previously demonstrated that β-catenin's differential usage of the Kat3 transcriptional coactivator cyclic AMP-response element binding protein-binding protein (CBP) over its highly homologous coactivator p300 increases self-renewal and suppresses differentiation in other types of cancer. AIM/METHODS:To investigate Wnt-mediated carcinogenesis in PDAC, we have used the specific small molecule CBP/β-catenin antagonist, ICG-001, which our lab identified and has extensively characterized, to examine its effects in human pancreatic cancer cells and in both an orthotopic mouse model and a human patient-derived xenograft (PDX) model of PDAC. RESULTS/CONCLUSION:We report for the first time that K-Ras activation increases the CBP/β-catenin interaction in pancreatic cancer; and that ICG-001 specific antagonism of the CBP/β-catenin interaction sensitizes pancreatic cancer cells and tumors to gemcitabine treatment. These effects were associated with increases in the expression of let-7a microRNA; suppression of K-Ras and survivin; and the elimination of drug-resistant cancer stem/tumor-initiating cells

Active Pneumatic Suspension for Future Autonomous Vehicles: Design, Prove of Concept and Hardware-in-the-Loop Simulations

In this article, we present a new concept of an active air spring, which can apply pressure and tension forces independently of its deflection. The active strut mitigates body oscillations and improves the driving comfort making it attractive for autonomous driving to avoid motion sickness. The model of the active air spring system and the controller design are described. Furthermore, the suitability of the actuator concept for use in an active chassis is shown. Finally, we show results of hardware-in-the-loop simulations

Assessment of the vitamin D status and its determinants in young healthy students from Palestine

The global prevalence of vitamin D deficiency is high. Poor vitamin D status, especially in women, has been reported in several countries in the Middle East despite adequate year-round sunlight for vitamin D synthesis. However, data on vitamin D status in Palestine are scarce. The aim of this cross-sectional study was to evaluate vitamin D status based on serum concentrations of 25-hydroxycholecalciferol [25-(OH)D] among young healthy Palestinian students (18–27 years) and to assess associations between 25-(OH)D concentrations and several predictors. The mean 25-(OH)D concentration of women (n 151) was 27⋅2 ± 14⋅5 nmol/l, with the majority having insufficient (31⋅1 %) or deficient (<60 %) 25-(OH)D status. Only 7 % of women achieved sufficient or optimal 25-(OH)D status. In contrast, men (n 52) had a mean 25-(OH)D concentration of 58⋅3 ± 14⋅5 nmol/l, with none classified as deficient, and most obtaining sufficient (55⋅8 %) or even optimal 25-(OH)D status (11⋅5 %). Among women, 98 % wore a hijab and 74 % regularly used sunscreen. Daily dietary vitamin D intake (3-d 24-h recalls) was 45⋅1 ± 36⋅1 IU in the total group (no sex differences). After adjustment, multiple linear regression models showed significant associations between 25-(OH)D concentrations and the use of supplements (B = 0⋅069; P = 0⋅020) and dietary vitamin D (B = 0⋅001; P = 0⋅028). In gender-stratified analysis, the association between supplement use and 25-(OH)D concentrations was significant in women (B = 0⋅076; P = 0⋅040). The vitamin D status of women in the present cohort is critical and appears to be mainly due to wearing a hijab, regular use of sunscreen and low dietary vitamin D intake. The vitamin D status of the women should be improved by taking vitamin D containing supplements or fortified foods

Teaching ultrasound in a curricular course according to certified EFSUMB standards during undergraduate medical education: a prospective study

Background: As a non-invasive and readily available diagnostic tool, ultrasound is one of the most important imaging techniques in medicine. Ultrasound is usually trained during residency preferable according to German Society of Ultrasound in Medicine (DEGUM) standards. Our curriculum calls for undergraduate training in ultrasound of medical students in their 4th year of undergraduate education. An explorative pilot study evaluated the acceptance of this teaching method, and compared it to other practical activities in medical education at Muenster University. Methods: 240 medical students in their 4th year of undergraduate medical education participated in the training and completed a pre- and post-questionnaire for self-assessment of technical knowledge, self-assurance of the procedure, and motivation in performing ultrasound using a Likert scale. Moreover, students were asked about their interest in pursuing a career in internal medicine. To compare this training to other educational activities a standardized online evaluation tool was used. A direct observation of procedural skills assessment (DOPS) for the first time applied on ultrasound aimed to independently assess the success of our teaching method. Results: There was a significant increase in technical knowledge and self-assurance (p < 0.001) of the students’ self-assessments. The clinical relevance and self-motivation of the teaching were evaluated positively. The students’ DOPS results demonstrated proficiency in the understanding of anatomic structures shown in ultrasonographic images, including terminology, machine settings, and transducer frequencies. Conclusions: Training ultrasound according to certified DEGUM standards was successful and should be offered in undergraduate medical education. The evaluation of the course affirmed the necessity, quality and clinical relevance of the course with a top ranking score of hands-on training courses within the educational activities of the Medical Faculty of Muenster.<br

Data quality and information loss in standardised interpolated path analysis : quality measures and guidelines

Standardised interpolated path analysis (SIPA) is a method to investigate negotiation processes making different negotiation histories comparable. Due to its interpolation approach, researchers employing SIPA must take data quality and potential information loss into account to maximise the methods explanatory power. This paper presents quality measures and applies them to two negotiation datasets for deriving meaningful boundaries. Using these quality measures enables researchers to compare SIPA across segmentations, variables, and datasets also providing outlier analysis

New instruments of administrative procedure in Germany? : between acceptance and mediation

Disturbance of intestinal wound closure leads to insufficient anastomotic healing and is associated with considerable morbidity following colorectal resections. Matrix metalloproteinases (MMPs) play a crucial role in regulation of wound closure. Here fluorescence endoscopy was evaluated for assessment of MMP-2/-9 expression during failed intestinal anastomotic healing.Distal colonic anastomoses were performed as a model for disturbed healing in 36 Balb/c mice. Healing was evaluated endoscopically, macroscopically, and histologically after 1, 3 and 5 days. For detection of MMP-2/-9 expression fluorescence endoscopy (FE) was used following i.v.-administration of a Cy5.5-labeled MMP-2/-9 specific tracer. FE was complemented by quantification of the fluorescence signal using the MS-FX PRO Optical Imaging System. An overall leakage score was calculated and correlated with the results of FE.With increasing incidence of anastomotic leakage from POD1 (17%) to POD5 (83%) the uptake of the MMP tracer gradually increased (signal-to-noise ratio (SNR), POD1: 17.91 ± 1.251 vs. POD3: 30.56 ± 3.03 vs. POD5: 44.8 ± 4.473, P<0.0001). Mice with defective anastomotic healing showed significantly higher uptake compared to non-defective (SNR: 37.37± 3.63 vs. 26.16± 3.635, P = 0.0369). White light endoscopy and FE allowed evaluation of anastomotic healing and visualization of mucosal MMPs in vivo. Using FE based detection of MMPs in the anastomosis, an overall positive predictive value of 71.4% and negative predictive value of 66.6% was calculated for detection of anastomotic leakage.During disturbed anastomotic healing increased expression of MMP-2/-9 was observed in the anastomotic tissue. Fluorescence endoscopy for detection of MMP-2/-9 during the healing process might be a promising tool for early identification of anastomotic leakage

Limited Correlation of Shotgun Metagenomics Following Host Depletion and Routine Diagnostics for Viruses and Bacteria in Low Concentrated Surrogate and Clinical Samples

The etiologic cause of encephalitis, meningitis or meningo-encephalitis is unknown in up to 70% of cases. Clinical shotgun metagenomics combined with host depletion is a promising technique to identify infectious etiologies of central nervous system (CNS) infections. We developed a straightforward eukaryotic host nucleic acid depletion method that preserves intact viruses and bacteria for subsequent shotgun metagenomics screening of clinical samples, focusing on cerebrospinal fluid (CSF). A surrogate CSF sample for a CNS infection paradigm was used to evaluate the proposed depletion method consisting of selective host cell lysis, followed by enzymatic degradation of the liberated genomic DNA for final depletion with paramagnetic beads. Extractives were subjected to reverse transcription, followed by whole genome amplification and next generation sequencing. The effectiveness of the host depletion method was demonstrated in surrogate CSF samples spiked with three 1:100 dilutions of Influenza A H3N2 virus (qPCR Ct-values 20.7, 28.8, &gt;42/negative). Compared to the native samples, host depletion increased the amount of the virus subtype reads by factor 7127 and 132, respectively, while in the qPCR negative sample zero vs. 31 (1.4E-4 %) virus subtype reads were detected (native vs. depleted). The workflow was applied to thirteen CSF samples of patients with meningo-/encephalitis (two bacterial, eleven viral etiologies), a serum of an Andes virus infection and a nose swab of a common cold patient. Unlike surrogate samples, host depletion of the thirteen human CSF samples and the nose swab did not result in more reads indicating presence of damaged pathogens due to, e.g., host immune response. Nevertheless, previously diagnosed pathogens in the human CSF samples (six viruses, two bacteria), the serum, and the nose swab (Human rhinovirus A31) were detected in the depleted and/or the native samples. Unbiased evaluation of the taxonomic profiles supported the diagnosed pathogen in two native CSF samples and the native and depleted serum and nose swab, while detecting various contaminations that interfered with pathogen identification at low concentration levels. In summary, damaged pathogens and contaminations complicated analysis and interpretation of clinical shotgun metagenomics data. Still, proper consideration of these issues may enable future application of metagenomics for clinical diagnostics