Rainwater harvesting for small-holder horticulture in Namibia: design of garden variants and assessment of climate change impacts and adaptation
- The design of rainwater harvesting based gardens requires considering current climate but also climate change during the lifespan of the facility. The goal of this study is to present an approach for designing garden variants that can be safely supplied with harvested rainwater, taking into account climate change and adaptation measures. In addition, the study presents a methodology to quantify the effects of climate change on rainwater harvesting based gardening. Results of the study may not be accurate due to the assumptions made for climate projections and may need to be further refined. We used a tank flow model and an irrigation water model. Then we established three simple climate scenarios and analyzed the impact of climate change on harvested rain and horticulture production for a semi-arid region in northern Namibia. In the two climate scenarios with decreased precipitation and medium/high temperature increase; adaptation measures are required to avoid substantial decreases in horticulture production. The study found that the most promising adaptation measures to sustain yields and revenues are a more water efficient garden variant and an enlargement of the roof size. The proposed measures can partly or completely compensate the negative impacts of climate change.
"Great Technology, Football and..." : Malaysian Language Learners' Stereotypes about Germany
Zuraidah Binti Mohd Don
Sau Cheong Loh
- This study focuses on stereotypes about Germany, its culture and people, held by learners of German in a big public university in Malaysia. It examines not only the stereotypical representations of the target language country but also assesses its favourability and salience, which has not been done previously. The findings revealed that the students' stereotypes about Germany were varied and diverse. Also, they were overwhelmingly positive. The top three salient categories of images about Germany were related to technology, famous personalities – for the most part football players and scientists – and cars. The findings also indicated that very few references had been made to German culture and to its great cultural figures. The results of the present study suggest that students could benefit from a wider and deeper exposure to German culture in the language classroom.
"Brücke dreht sich um!" : A Deconstructionist Reading of Kafka's "Die Brücke"
- Franz Kafka's (1883-1924) "Die Brücke" is one of the less well-known texts by one of the most prolific authors of literary modernity. However, this short prose text embodies prevalent questions of literary modernity and philosophy as it reflects the crisis of language in regard of identity, communication, and literary production. Placed in the context of fin-de-siècle's discourse of language crisis, this article provides a dialogue between Kafka's "Die Brücke" and Hannah Arendt's (1906-1975) philosophy of thinking and speaking in "The Life of the Mind". Contrary to Arendt's understanding of the metaphor as "a carrying over" between the mental activities of the solitude thinker and a reconciliation with the pluralistic world shared with others, this article argues for a deconstructionist reading of "Die Brücke" as a tool to reevaluate Arendt"s notion of a shared human experience ensured through language and illustrates the advantages of poetic texts within philosophical discourses.
Creating a unique, multi-stakeholder Paediatric Oncology Platform to improve drug development for children and adolescents with cancer
Mary Brigid Bradley-Garelik
- Seven years after the launch of the European Paediatric Medicine Regulation, limited progress in paediatric oncology drug development remains a major concern amongst stakeholders – academics, industry, regulatory authorities, parents, patients and caregivers. Restricted increases in early phase paediatric oncology trials, legal requirements and regulatory pressure to propose early Paediatric Investigation Plans (PIPs), missed opportunities to explore new drugs potentially relevant for paediatric malignancies, lack of innovative trial designs and no new incentives to develop drugs against specific paediatric targets are some unmet needs. Better access to new anti-cancer drugs for paediatric clinical studies and improved collaboration between stakeholders are essential. The Cancer Drug Development Forum (CDDF), previously Biotherapy Development Association (BDA), with Innovative Therapy for Children with Cancer Consortium (ITCC), European Society for Paediatric Oncology (SIOPE) and European Network for Cancer Research in Children and Adolescents (ENCCA) has created a unique Paediatric Oncology Platform, involving multiple stakeholders and the European Union (EU) Commission, with an urgent remit to improve paediatric oncology drug development. The Paediatric Oncology Platform proposes to recommend immediate changes in the implementation of the Regulation and set the framework for its 2017 revision; initiatives to incentivise drug development against specific paediatric oncology targets, and repositioning of drugs not developed in adults. Underpinning these changes is a strategy for mechanism of action and biology driven selection and prioritisation of potential paediatric indications rather than the current process based on adult cancer indications. Pre-competitive research and drug prioritisation, early portfolio evaluation, cross-industry cooperation and multi-compound/sponsor trials are being explored, from which guidance for innovative trial designs will be provided.
Structure and regulatory interactions of the cytoplasmic terminal domains of serotonin transporter
Thomas C. Schwarz
Ahmad Reza Mehdipour
Satinder K. Singh
Harald H. Sitte
Lucy R. Forrest
- Uptake of neurotransmitters by sodium-coupled monoamine transporters of the NSS family is required for termination of synaptic transmission. Transport is tightly regulated by protein–protein interactions involving the small cytoplasmic segments at the amino- and carboxy-terminal ends of the transporter. Although structures of homologues provide information about the transmembrane regions of these transporters, the structural arrangement of the terminal domains remains largely unknown. Here, we combined molecular modeling, biochemical, and biophysical approaches in an iterative manner to investigate the structure of the 82-residue N-terminal and 30-residue C-terminal domains of human serotonin transporter (SERT). Several secondary structures were predicted in these domains, and structural models were built using the Rosetta fragment-based methodology. One-dimensional 1H nuclear magnetic resonance and circular dichroism spectroscopy supported the presence of helical elements in the isolated SERT N-terminal domain. Moreover, introducing helix-breaking residues within those elements altered the fluorescence resonance energy transfer signal between terminal cyan fluorescent protein and yellow fluorescent protein tags attached to full-length SERT, consistent with the notion that the fold of the terminal domains is relatively well-defined. Full-length models of SERT that are consistent with these and published experimental data were generated. The resultant models predict confined loci for the terminal domains and predict that they move apart during the transport-related conformational cycle, as predicted by structures of homologues and by the “rocking bundle” hypothesis, which is consistent with spectroscopic measurements. The models also suggest the nature of binding to regulatory interaction partners. This study provides a structural context for functional and regulatory mechanisms involving SERT terminal domains.
Randomized controlled multicenter trial on the effectiveness of the collagen hemostat Sangustop® compared with a carrier-bound fibrin sealant during liver resection (ESSCALIVER study, NCT00918619)
Andre L. Mihaljevic
Wolfgang E. Thasler
Markus K. Diener
Wolf Otto Bechstein
- Background: Despite improvements in liver surgery over the past decades, hemostasis during hepatic resections remains challenging. This multicenter randomized study compares the hemostatic effect of a collagen hemostat vs. a carrier-bound fibrin sealant after hepatic resection.
Methods: Patients scheduled for elective liver resection were randomized intraoperatively to receive either the collagen hemostat (COLL) or the carrier-bound fibrin sealant (CBFS) for secondary hemostasis. The primary endpoint was the proportion of patients with hemostasis after 3 min. Secondary parameters were the proportions of patients with hemostasis after 5 and 10 min, the total time to hemostasis, and the complication rates during a 3 months follow-up period.
Results: A total of 128 patients were included. In the COLL group, 53 out of 61 patients (86.9 %) achieved complete hemostasis within 3 min after application of the hemostat compared to 52 out of 65 patients (80.0 %) in the CBFS group. The 95 % confidence interval for this difference [−6.0 %, 19.8 %] does not include the lower noninferiority margin (−10 %). Thus, the COLL treatment can be regarded as noninferior to the comparator. The proportions of patients with hemostasis after 3, 5, and 10 min were not significantly different between the two study arms. Postoperative mortality and morbidity were similar in both treatment groups.
Conclusion: The collagen hemostat is as effective as the carrier-bound fibrin sealant in obtaining secondary hemostasis during liver resection with a comparable complication rate.
Tricyclic guanidine alkaloids from the marine sponge Acanthella cavernosa that stabilize the tumor suppressor PDCD4
Johanna S. Blees
Magdalena M. Bayer
Nancy H. Colburn
Cheryl L. Thomas
Curtis J. Henrich
Megan L. Peach
James B. McMahon
Kirk R. Gustafson
- A cell-based high-throughput screen that assessed the cellular stability of a tumor suppressor protein PDCD4 (Programmed cell death 4) was used to identify a new guanidine-containing marine alkaloid mirabilin K (3), as well as the known compounds mirabilin G (1) and netamine M (2). The structures of these tricyclic guanidine alkaloids were established from extensive spectroscopic analyses. Compounds 1 and 2 inhibited cellular degradation of PDCD4 with EC50 values of 1.8 μg/mL and 2.8 μg/mL, respectively. Mirabilin G (1) and netamine M (2) are the first marine natural products reported to stabilize PDCD4 under tumor promoting conditions.
Resveratrol post-transcriptionally regulates pro-inflammatory gene expression via regulation of KSRP RNA binding activity
Verena M. Dirsch
- Resveratrol shows beneficial effects in inflammation-based diseases like cancer, cardiovascular and chronic inflammatory diseases. Therefore, the molecular mechanisms of the anti-inflammatory resveratrol effects deserve more attention. In human epithelial DLD-1 and monocytic Mono Mac 6 cells resveratrol decreased the expression of iNOS, IL-8 and TNF-α by reducing mRNA stability without inhibition of the promoter activity. Shown by pharmacological and siRNA-mediated inhibition, the observed effects are SIRT1-independent. Target-fishing and drug responsive target stability experiments showed selective binding of resveratrol to the RNA-binding protein KSRP, a central post-transcriptional regulator of pro-inflammatory gene expression. Knockdown of KSRP expression prevented resveratrol-induced mRNA destabilization in human and murine cells. Resveratrol did not change KSRP expression, but immunoprecipitation experiments indicated that resveratrol reduces the p38 MAPK-related inhibitory KSRP threonine phosphorylation, without blocking p38 MAPK activation or activity. Mutation of the p38 MAPK target site in KSRP blocked the resveratrol effect on pro-inflammatory gene expression. In addition, resveratrol incubation enhanced KSRP-exosome interaction, which is important for mRNA degradation. Finally, resveratrol incubation enhanced its intra-cellular binding to the IL-8, iNOS and TNF-α mRNA. Therefore, modulation of KSRP mRNA binding activity and, thereby, enhancement of mRNA degradation seems to be the common denominator of many anti-inflammatory effects of resveratrol.
Direct observation of mobility state transitions in RNA trajectories by sensitive single molecule feedback tracking
Tim P. Kaminski
Jennifer S. Rinne
- Observation and tracking of fluorescently labeled molecules and particles in living cells reveals detailed information about intracellular processes on the molecular level. Whereas light microscopic particle observation is usually limited to two-dimensional projections of short trajectory segments, we report here image-based real-time three-dimensional single particle tracking in an active feedback loop with single molecule sensitivity. We tracked particles carrying only 1-3 fluorophores deep inside living tissue with high spatio-temporal resolution. Using this approach, we succeeded to acquire trajectories containing several hundred localizations. We present statistical methods to find significant deviations from random Brownian motion in such trajectories. The analysis allowed us to directly observe transitions in the mobility of ribosomal (r)RNA and Balbiani ring (BR) messenger (m)RNA particles in living Chironomus tentans salivary gland cell nuclei. We found that BR mRNA particles displayed phases of reduced mobility, while rRNA particles showed distinct binding events in and near nucleoli.
Phenotypic variation of 38 European Ambrosia artemisiifolia populations measured in a common garden experiment
Marion Carmen Leiblein-Wild
- The knowledge of phenotypic variation in the European range of the highly allergenic Ambrosia artemisiifolia L. (common ragweed) is not entirely complete, even though it is an invasive species of utmost concern. We hypothesized the prevalence of phenotypic differentiations between common ragweed populations in the introduced range, and we assumed that those differentiations were related to environmental conditions at the points of origin. Using a common garden experiment, we investigated biomass allocation, growth rates, and flowering phenology of 38 European common ragweed populations originating from a major geographical gradient. We observed considerable phenotypic variation in growth parameters and flowering phenology, e.g. mean aboveground biomass varied from 23.3 to 47.3 g between the populations. We were able to relate most measured traits with environmental parameters prevailing at the points of origin. For example, early growth of ruderal populations was highly correlated with temperature and precipitation at the point of origin. Late growth and flowering phenology were highly correlated with latitude, i.e. individuals from northern populations grew smaller and flowered and dispersed their pollen and seeds up to 5 weeks earlier than individuals from southern populations. We also found a longitudinal gradient in flowering phenology which has not yet been described. The existence of such a high variability in the introduced range may facilitate further range expansion. We suggest that the correlation with environmental variables rests upon genetic variation possibly due to adaptations to the respective environment. To clarify if such adaptation results from multiple events of introduction or as evolutionary response after introduction, genetic investigations are needed.