Refine
Year of publication
- 2014 (1214) (remove)
Document Type
- Article (588)
- Part of Periodical (163)
- Working Paper (149)
- Book (134)
- Doctoral Thesis (86)
- Report (27)
- Part of a Book (23)
- Conference Proceeding (18)
- Review (10)
- Preprint (8)
Language
- English (1214) (remove)
Keywords
- taxonomy (21)
- new species (19)
- Syntax (11)
- Inversionsfigur (10)
- Multistability (10)
- Multistable figures (10)
- Wahrnehmungswechsel (10)
- morphology (8)
- Bantusprachen (7)
- Benjamin, Walter (7)
Institute
- Medizin (231)
- Wirtschaftswissenschaften (149)
- Center for Financial Studies (CFS) (131)
- Physik (101)
- Biowissenschaften (88)
- Sustainable Architecture for Finance in Europe (SAFE) (86)
- House of Finance (HoF) (82)
- Biochemie und Chemie (48)
- Geowissenschaften (41)
- Gesellschaftswissenschaften (33)
Remembering a Legend: Chinua Achebe recaptures for the literary world the inimitable legacies of Chinua Achebe (1930-2013), Africa's leading novelist and literary philosopher of the 20th century. It addresses the questions of Achebe's role in establishing the African art of the novel, his theories and standards for the criticism of African writing. The volume articulates unequivocally how Achebe provided the message and pioneered a confident voice to African writers to express the message with audacity; repudiate without equivocation, any form of distortions of African past and present realities. The essays remind the reader how Achebe brought to the field of world literature new perspectives and vitality that distinguished the African art of storytelling from imaginative creativities elsewhere. This volume presents Achebe's articulation of the traditional and modern in African narrative techniques-linking the skills of the traditional artist (oral performer) to those of the modern writer; how the modern African creative artist can embellish his/her art with oral resources such as folktales, proverbs, sayings, festivals, songs, riddles, and myths. Chinua Achebe's unique distinctions as a novelist lie in the areas of informed vision and artistic integrity. His greatest legacy to 20th century world literature probably is his pioneer role in the 'nativization' and ingenious use of the English language. The exceptional genius of Achebe touched many traditional and cultural bases in his fiction, essays, and memoirs. The critical responses to Achebe's works in this book, address adequately almost every aspect of his creative imagination and craftsmanship. The reader will find in this convenient volume several seminal studies by two eminent scholars of Achebe's intriguing genius that authenticate him as among the best literary craftsmen of the 20th century and undeniably Africa's best.
Especially in developing countries credit constraints are often perceived as one of the most important market frictions constraining firm innovation and growth. Huge amounts of public money are being devoted to the removal of such constraints but their effectiveness is still subject to an intense policy debate. This paper contributes to this debate by analysing the effects of the Brazilian Development Bank (BNDES) loans. It finds that, before receiving BNDES support, granted firms are indeed more credit constrained than comparable non-granted firms. It also finds that BNDES support allows granted firms to achieve the same level of performance as similar non-granted firms that are not credit constrained. However, it does not allow granted firms to outperform similar non-granted ones.
Since Inhibitor of Apoptosis (IAP) proteins are frequently dysregulated in different cancer entities and contribute to apoptosis resistance, pharmacological IAP antagonists are considered to be promising agents for the future development of cancer treatment strategies. IAP antagonists are small-molecule drugs that have been designed to mimic the interaction site of IAP proteins with their endogenous inhibitor Second mitochondrial activator of caspases (SMAC). Thus, they are frequently referred to as SMAC mimetics. Treatment with SMAC mimetics engages an apoptotic program in cancers by affecting different components of the apoptotic machinery. Besides disinhibition of caspases, SMAC mimetics trigger non-canonical nuclear factor-κB (NF-κB) signaling, which induces upregulation of tumor necrosis factor (TNF) α and other NF-κB target genes. In particular, TNFα production has been closely linked to the induction of SMAC mimetic-mediated cell death. The TNFα-dependent para/autocrine loop facilitates the formation of a cytosolic complex consisting of caspase-8, Fas-associated death domain (FADD) and Receptor-interacting protein (RIP) 1, which serves as caspase-8 activation platform and ultimately triggers induction of apoptosis. In the present study, we use the small-molecule bivalent SMAC mimetic BV6 to analyze SMAC-stimulated NF-κB signaling in cancer cell lines of different entities. Interestingly, we identify two novel NF-κB-regulated factors that are both required for SMAC mimetic-induced apoptosis in a context-dependent manner. First, we show that NF-κB-dependent upregulation of death receptor 5 (DR5) can serve as an alternative mechanism of BV6-mediated cell death. We demonstrate that BV6 treatment induces NF-κB-dependent but largely TNFα -independent apoptosis in A172 glioblastoma cells. By using an unbiased whole genome expression analysis approach, we identify DR5 as a critical NF-κB target gene, which substitutes TNFα and is indispensable for BV6-initated cell death in A172 cells. Second, we demonstrate that Interferon regulatory factor (IRF) 1 is required for BV6-induced TNFα production and apoptosis. Our study provides evidence that IRF1 closely cooperates with the NF-κB network in BV6-mediated cell death and additionally alters expression of selective SMAC mimetic-induced target genes. Furthermore, we show that BV6 treatment triggers secretion of a set of proinflammatory cytokines and increases attraction of monocytes to BV6-treated tumor cells in an IRF1-dependent manner. In summary, our work supports the notion that NF-κB-regulated factors are critically required for SMAC mimetic-initiated apoptosis. We show that IRF1 is indispensable for TNFα production and cell death in BV6-sensitive cell lines and that also DR5 can serve as a proapoptotic NF-κB-controlled factor in BV6-induced apoptosis besides TNFα. Furthermore, this study contributes to an improved understanding on non-apoptotic functions of SMAC mimetics, as IRF1 additionally influences expression levels of proinflammatory cytokines and attraction of immune cells. Thus, our work provides novel insights into the regulation of SMAC mimetic-induced signaling events, which is crucial for the translation of SMAC mimetics for use in clinical application.
Molecular signaling networks, organized in discrete subsets of proteins in space and time, represent the major principle by which the cell achieves its functional specificity and homeostasis. Complex network organization is preserved by numerous mechanisms, including sequestration of proteins into specific subcellular compartments (eg. organelles), post-translational modifications and most importantly by balanced timing of their biosynthesis and turnover. Two routes of protein degradation, which are fundamentally quite different, are proteasomal and lysosomal-mediated destruction. The latter not only governs degradation of molecules that passed through endocytic or secretory process (trafficking from plasma membrane or Golgi compartment), but also the degradation of cytoplasmic molecules that have been sequestered by a process called macroautophagy (henceforth autophagy). Recently our understanding of autophagic regulatory mechanisms has increased significantly, as molecular details of how autophagy contributes to the degradation of proteins (old, misfolded or aggregated), damaged organelles or pathogens have been deciphered. Initially described as bulk, nonspecific membrane sequestration process induced primarily by nutrient deprivation, autophagy is now known to be selective in terms of cargo recognition and integration into dynamic cellular membrane trafficking system.
My work has addressed the fundamental question of how small ubiquitin-like modifiers LC3/GABARAP, that are conjugated to the autophagic membranes, function within the process of cargo selection and crosstalk between autophagic and endocytic membrane trafficking events. We have employed an initial yeast twohybrid screen to identify LC3/GABARAP interacting partners. Using this technique, we have identified several novel autophagy receptor proteins, mitochondrial protein Nix (BNIP3L), and adaptor proteins, including Rab GTPase activating proteins (TBC family of proteins). Through a conserved LC3 interacting region (LIR), Nix, Rab GAPs and other autophagy adaptor/receptor molecules share a common mode of binding to LC3/GABARAP. However, in contrast to Nix, which specifically facilitates removal of mitochondria in maturing erythrocytes, Rab GAP proteins preferably regulate the dynamics of autophagosome formation and maturation as well as sorting of cargo. Fourteen out of 36 screened Rab GAPs interacted with LC3/GABARAPs. Importantly, identified Rab GAPs are clustered in different regulatory nodes according to the conservation of their GAP domain hence they impact various cellular membrane compartments and organelles, marked by specific subsets of small Rab GTPases. Identification of Rab GAPs that are directly involved in autophagy via binding to LC3 was the first report that clearly pointed to a broader implication of autophagy in all aspects of cellular membrane trafficking. Currently, only few of Rab GAPs are studied in context of autophagy regulation, while large number of them requires further functional characterization.
I have identified two LIR motifs in TBC1D5, Rab7 GAP. LIR1 has also the ability to interact with retromer complex subunit, Vps29. Using several functional assays I have shown that this motif, as well as catalytic Arg within GAP domain are particularly important for function of TBC1D5 in retrograde transport of CI-M6PR from endosomes to the trans-Golgi network (TGN). I have also shown that TBC1D5 binds to LC3 and Vps29 in mutually exclusive way and that Thr at the position 1 and Phe at position 5 of LIR1 motif are both required for TBC1D5 interaction with Vps29. Upon autophagy induction TBC1D5 dissociates from retromer, and associates with autophagic vesicles, while silencing of TBC1D5 significantly impairs autophagic flux. These findings led to the hypothesis that LIR interacting surface on TBC1D5 acts as molecular switch for dual function of TBC1D5. This also indicated that similar surfaces for LIR interaction (similarly to ubiquitin-like domains) are present on proteins other than LC3, and pointed to a dual functionality of the LIR sequence within both endocytic and autophagic pathways.
Following these initial studies, I have also shown that TBC1D5 interacts with AP2 complex subunit AP2M1, and that this interaction plays critical role in TBC1D5-dependent trafficking of Atg9. It is known that Atg9, the only trans-membrane autophagic protein, plays essential role in initiation of autophagy and growth of nascent phagophore membranes. However, machinery that specifically recruits Atg9 traffic carriers to the site of autophagosomes was not known. I subsequently demonstrated that TBC1D5 associates not only with LC3, but also with Atg9 traffic carriers and major initiatory kinase ULK1 during autophagy, while retromer failed to do so. Association of TBC1D5 with Atg9 was dependent on presence of AP2 complex, and on functional clathrin-mediated endocytosis (CME). Based on these and previous findings, model was proposed, that upon induction of autophagy TBC1D5 re-routes Atg9-containing clathrin vesicles from plasma membrane to the site of autophagosome. This led us to the better understanding of TBC1D5 function, but also to the first molecular cue that Atg9 traffics within clathrin-coated vesicles (CCVs). In fact, mutation of Leu-Leu motif within N terminus of Atg9, that potentially mediates interaction with adaptor protein complexes, led to enrichment of Atg9 on plasma membrane and in TGN. This suggested that the sorting motif could be important for interaction of Atg9 with AP2 and AP1 complex, as well. More importantly, TBC1D5 and Atg9 could be directly involved in dynamic regulation of growth factor receptor sorting during autophagy, thus explaining vital role of autophagy in organism development and pathogenesis.
In summary, the work contained within my thesis provides data on the mechanism by which autophagy adaptor proteins participate in cargo selection and regulation of trafficking during autophagy. Firstly, the LIR motif can target proteins or organelles for autophagic degradation (eg. Nix). Secondly, specific LIR motifs can play essential function in recruiting membrane trafficking regulatory proteins that subsequently facilitate phagophore expansion (eg. TBC1D5). Thirdly, by means of reorganization of different protein assemblies (eg. TBC1D5-VPS29 vs. TBC1D5-LC3-Atg9), dynamics of membrane remodeling mediated by Rab GTPases is kept in control during autophagy, thus keeping the organelle integrity and balance within cellular lipid sources unaffected.
This dataset represents a registry of species that are not native but recorded to live in the wild of at least one of the four countries that comprise the Two Seas Area, i.e. Great Britain, France, Belgium and the Netherlands. For each of the 6,661 species, subspecies and hybrids listed, we provide detailed information on its status in each country, taxonomic affiliation and environment inhabited. The data were collected by review of 36 web- and print-based sources over an eight-month period. Further systematic scanning of three of the most relevant scientific journals, i.e. Neobiota, Aquatic Invasions and BioInvasions Records, recovered 19 additional relevant publications from which information was included in the registry. As a result, the registry will serve as a basis for developing effective, cross-boundary strategies to manage and control non-native species, which can have severe ecological and economic impacts. The registry can further be used as a general reference for both scientists and practitioners, as well as a tool to assess reliability and comprehensiveness of other well-known databases such as the DAISIE portal.
Introduction: Defects in the DNA mismatch repair (MMR) protein MLH1 are frequently observed in sporadic and hereditary colorectal cancers (CRC). Affected tumors generate much less metastatic potential than the MLH1 proficient forms. Although MLH1 has been shown to be not only involved in postreplicative MMR but also in several MMR independent processes like cytoskeletal organization, the connection between MLH1 and metastasis remains unclear. We recently identified non-erythroid spectrin αII (SPTAN1), a scaffolding protein involved in cell adhesion and motility, to interact with MLH1. In the current study, the interaction of MLH1 and SPTAN1 and its potential consequences for CRC metastasis was evaluated.
Methods: Nine cancer cell lines as well as fresh and paraffin embedded colon cancer tissue from 12 patients were used in gene expression studies of SPTAN1 and MLH1. Co-expression of SPTAN1 and MLH1 was analyzed by siRNA knock down of MLH1 in HeLa, HEK293, MLH1 positive HCT116, SW480 and LoVo cells. Effects on cellular motility were determined in MLH1 deficient HCT116 and MLH1 deficient HEK293T compared to their MLH1 proficient sister cells, respectively.
Results: MLH1 deficiency is clearly associated with SPTAN1 reduction. Moreover, siRNA knock down of MLH1 decreased the mRNA level of SPTAN1 in HeLa, HEK293 as well as in MLH1 positive HCT116 cells, which indicates a co-expression of SPTAN1 by MLH1. In addition, cellular motility of MLH1 deficient HCT116 and MLH1 deficient HEK293T cells was impaired compared to the MLH1 proficient sister clones. Consequently, overexpression of SPTAN1 increased migration of MLH1 deficient cells while knock down of SPTAN1 decreased cellular mobility of MLH1 proficient cells, indicating SPTAN1-dependent migration ability.
Conclusions: These data suggest that SPTAN1 levels decreased in concordance with MLH1 reduction and impaired cellular mobility in MLH1 deficient colon cancer cells. Therefore, aggressiveness of MLH1-positive CRC might be related to SPTAN1.
Highly promising preclinical data obtained in cultured cells and in nude mice bearing xenografts contrast with the rather modest clinical efficacy of Polo-like kinase 1 (Plk1) inhibitors. In the present study, we investigated if Plk1 might be a suitable target in hepatocellular carcinoma (HCC) and if a genetically engineered mouse tumor model that well reflects the tumor cell and micro-environmental features of naturally occurring cancers might be suitable to study anti-Plk1 therapy. Analysis of Plk1 expression in human HCC samples confirmed that HCC express much higher Plk1 levels than the adjacent normal liver tissue. Inhibition of Plk1 by an adenovirus encoding for a short hairpin RNA against Plk1 or by the small-molecule inhibitor BI 2536 reduced the viability of HCC cell lines and inhibited HCC xenograft progression in nude mice. Treatment of transforming growth factor (TGF) α/c-myc bitransgenic mice with BI 2536 during hepatocarcinogenesis reduced the number of dysplastic foci and of Ki-67-positive cells within the foci, indicating diminished tumorigenesis. In contrast, BI 2536 had no significant effect on HCC progression in the transgenic mouse HCC model as revealed by magnetic resonance imaging. Measurement of BI 2536 by mass spectrometry revealed considerably lower BI 2536 levels in HCC compared with the adjacent normal liver tissue. In conclusion, low intratumoral levels are a novel mechanism of resistance to the Plk1 inhibitor BI 2536. Plk1 inhibitors achieving sufficient intratumoral levels are highly promising in HCC treatment.
The structure of the title compound, C8H16N4, which consists of four fused seven-membered rings, has been redetermined at 173 K. This redetermination corrects the orientation of two H atoms, which were located at unrealistic positions in the original room-temperature study [Murray-Rust (1974[Murray-Rust, P. (1974). J. Chem. Soc. Perkin Trans. 2, pp. 1136-1141.]). J. Chem. Soc. Perkin Trans. 2, pp. 1136–1141]. The complete molecule is generated by -42m symmetry, with one quarter of a molecule [one N atom (site symmetry m), two C atoms (one with site symmetry m and the other with site symmetry 2) and two H atoms] in the asymmetric unit. No directional interactions beyond van der Waals contacts are apparent in the crystal structure.
Tapinesthis inermis Simon, 1882, the only species in the genus, is widely distributed in western Europe. This redescription provides the first information on the ultrastructure of the species using SEM. The morphology of the spinnerets, tarsal claws and tarsal organs, and the internal structure of the female genitalia and the male palp are described and illustrated in detail. The combination of these structures is very similar to those encountered in some dysderoid spiders and supports the basal placement of Tapinesthis among Oonopinae. The phylogenetic relationships of the species are discussed. The only female among the three syntypes is designated as the lectotype.
Brain activity reveals exquisite coordination across spatial scales, from local microcircuits to brain-wide networks. Understanding how the brain represents, transforms and communicates information requires simultaneous recordings from distributed nodes of whole brain networks with single-cell resolution. Realizing multi-site recordings from communicating populations is hampered by the need to isolate clusters of interacting cells, often on a day-to-day basis. Chronic implantation of multi-electrode arrays allows long-term tracking of activity. Lithography on thin films provides a means to produce arrays of variable resolution, a high degree of flexibility, and minimal tissue displacement. Sequential application of surface arrays to monitor activity across brain-wide networks and subsequent implantation of laminar arrays to target specific populations enables continual refinement of spatial scale while maintaining coverage.
Das Schwerionenkollisionen Programm der Beschleuniger RHIC und LHC gibt Hinweise auf einen neuen Zustand hadronischer Materie --- das Quark-Gluon Plasma. Dieses zeichnet sich durch eine zumindest partielle Aufhebung des confinements aus, welches besagt, dass keine freien Quarks beochtbar sind.
Aus einer Beschreibung der experimentellen Daten mit relativistischer Hydrodynamik folgen weitere Eigenschaften. So geht das in einer Schwerionenkollision erzeugte Quark-Gluon Plasma nach sehr kurzer Zeit, etwa 1 fm/c, in ein zumindest lokales thermisches Gleichgewicht über. Durch die Lorentzkontraktion der beiden Schwerionen erwartet man, dass der Zustand direkt nach der Kollision durch eine Impulsanisotropie in der transversal-longitudinalen Ebene bestimmt wird. Somit setzt das Erreichen eines thermischen Gleichgewichts zunächst eine Isotropisierung voraus. Bisherige Studien haben gezeigt, dass gluonische Moden bei dieser Isotropisierung durch Verursachung einer chromo-Weibel Instabilität eine entscheidende Rolle spielen.
Weiterhin verhält sich das Quark-Gluon Plasma wie eine fast perfekte Flüssigkeit. Eine Berücksichtigung dissipativer Terme in der hydrodynamischen Beschreibung erfordert das Hinzufügen weiterer Terme zu den entsprechenden Bewegungsgleichungen. Diese sind proportional zu Transportkoeffizienten, welche durch die zugrunde liegende mikroskopische Theorie festgelegt sind.
Diese Theorie ist Quantenchromodynamik. Sie beschreibt die starke Wechselwirkung der Quarks und Gluonen und ist ein fundamentaler Baustein des Standardmodells der Teilchenphysik. Da im Regelfall Prozesse der starken Wechselwirkung nichtperturbativ sind, beschreiben wir QCD unter Verwendung einer Gitterregularisierung. Diese beruht auf einer Diskretisierung der vierdimensionalen Euklidischen Raumzeit durch einen Hyperkubus mit periodischen Randbedingungen und ermöglicht ein Lösen der QCD mit numerischen Methoden. Allerdings ist die Anwendung der Gittereichtheorie auf Systeme im thermischen Gleichgewicht beschränkt und kann somit keine Prozesse beschreiben, die auf Echtzeit basieren.
Transportkoeffizienten entsprechen Proportionalitätskoeffizienten, die die Relaxation einer Flüssigkeit oder eben eines Quark-Gluon Plasmas von einer kleinen Störung beschreiben. Damit sind sie unmittelbar mit der Zeit verknüpft. Über Kubo-Formeln lassen sie sich jedoch mit Gleichgewichtserwartungswerten retardierter Korrelatoren verknüpfen und werden so in Gitter QCD zugänglich.
In der vorliegenden Dissertation berechnen wir den Transportkoeffizienten κ in Gittereichtheorie für das Yang-Mills Plasma. Dabei nutzen wir aus, dass dieser Transportkoeffizient eine triviale analytische Fortsetzung vom retardierten zum Euklidischen Korrelator besitzt, welcher direkt in Gittereichtheorie zugänglich ist. Es ist die erste nichtperturbative Berechnung eines Transportkoeffizienten in QCD ohne weitere Annahmen, wie die Maximum Entropie Methode oder Ansätze, zu treffen.
Reading through the Charcoal Industry in Ethiopia : Production, Marketing, Consumption and Impact
(2014)
Studies in many African countries show that charcoal making is among the primary drivers of deforestation and subsequent land degradation. In the case of Ethiopia, charcoal is produced from state-owned (public) forests and woodlands. There is little regulatory intervention from the government side. Moreover, production is more traditional and the producers have little idea that charcoal can be produced efficiently with modern technologies. Although charcoal meets significant portion of urban households' energy needs in the country, and also support the livelihood of tens of thousands of rural households, it hardly attracted the attention of policy makers and development agents. A good majority of urban population who use charcoal on regular basis doesn't seem to know how charcoal is made, from where it comes, and its adverse environmental impacts. In cognizant of the potential environmental impact of charcoal production and marketing in the country, FSS commissioned this study with the objective to understand the environmental, social and economic implications of charcoal production, marketing and consumption in Ethiopia with aim to generate/increase awareness among the general public and incite a policy debate among concerned key stakeholders.
Emotional competence has an important influence on development in school. We hypothesized that reading and discussing children’s books with emotional content increases children’s emotional competence. To examine this assumption, we developed a literature-based intervention, named READING and FEELING, and tested it on 104 second and third graders in their after-school care center. Children who attended the same care center but did not participate in the emotion-centered literary program formed the control group (n = 104). Our goal was to promote emotional competence and to evaluate the effectiveness of the READING and FEELING program. Emotional competence variables were measured prior to the intervention and 9 weeks later, at the end of the program. Results revealed significant improvements in the emotional vocabulary, explicit emotional knowledge, and recognition of masked feelings. Regarding the treatment effect for detecting masked feelings, we found that boys benefited significantly more than girls. These findings underscore the assumption that children’s literature is an appropriate vehicle to support the development of emotional competence in middle childhood.
Species' geographical distributions are tracking latitudinal and elevational surface temperature gradients under global climate change. To evaluate the opportunities to track these gradients across space, we provide a first baseline assessment of the steepness of these gradients for the world's terrestrial birds. Within the breeding ranges of 9,014 bird species, we characterized the spatial gradients in temperature along latitude and elevation for all and a subset of bird species, respectively. We summarized these temperature gradients globally for threatened and non-threatened species and determined how their steepness varied based on species' geography (range size, shape, and orientation) and projected changes in temperature under climate change. Elevational temperature gradients were steepest for species in Africa, western North and South America, and central Asia and shallowest in Australasia, insular IndoMalaya, and the Neotropical lowlands. Latitudinal temperature gradients were steepest for extratropical species, especially in the Northern Hemisphere. Threatened species had shallower elevational gradients whereas latitudinal gradients differed little between threatened and non-threatened species. The strength of elevational gradients was positively correlated with projected changes in temperature. For latitudinal gradients, this relationship only held for extratropical species. The strength of latitudinal gradients was better predicted by species' geography, but primarily for extratropical species. Our findings suggest threatened species are associated with shallower elevational temperature gradients, whereas steep latitudinal gradients are most prevalent outside the tropics where fewer bird species occur year-round. Future modeling and mitigation efforts would benefit from the development of finer grain distributional data to ascertain how these gradients are structured within species' ranges, how and why these gradients vary among species, and the capacity of species to utilize these gradients under climate change.
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.
The success of invasive species has been explained by two contrasting but non-exclusive views: (i) intrinsic factors make some species inherently good invaders; (ii) species become invasive as a result of extrinsic ecological and genetic influences such as release from natural enemies, hybridization or other novel ecological and evolutionary interactions. These viewpoints are rarely distinguished but hinge on distinct mechanisms leading to different management scenarios. To improve tests of these hypotheses of invasion success we introduce a simple mathematical framework to quantify the invasiveness of species along two axes: (i) interspecific differences in performance among native and introduced species within a region, and (ii) intraspecific differences between populations of a species in its native and introduced ranges. Applying these equations to a sample dataset of occurrences of 1,416 plant species across Europe, Argentina, and South Africa, we found that many species are common in their native range but become rare following introduction; only a few introduced species become more common. Biogeographical factors limiting spread (e.g. biotic resistance, time of invasion) therefore appear more common than those promoting invasion (e.g. enemy release). Invasiveness, as measured by occurrence data, is better explained by inter-specific variation in invasion potential than biogeographical changes in performance. We discuss how applying these comparisons to more detailed performance data would improve hypothesis testing in invasion biology and potentially lead to more efficient management strategies.
Local protein synthesis has re-defined our ideas on the basic cellular mechanisms that underlie synaptic plasticity and memory formation. The population of messenger RNAs that are localised to dendrites, however, remains sparsely identified. Furthermore, neuronal morphological complexity and spatial compartmentalisation require efficient mechanisms for messenger RNA localisation and control over translational efficiency or transcript stability. 3’ untranslated regions, downstream from stop codons, are recognised for providing binding platforms for many regulatory units, thus encoding the processing of the above processes. The hippocampus, a part of the brain involved in the formation, organisation and storage of memories, provides a natural platform to investigate patterns of RNA localisation. The hippocampus comprises tissue layers, which naturally separate the principle neuronal cell bodies from their processes (axons and dendrites). Identifying the full-complement of localised transcripts and associated 3’UTR isoforms is of great importance to understand both basic neuronal functions and principles of synaptic plasticity. These findings can be used to study the properties of neuronal networks as well as to understand how these networks malfunction in neuronal diseases.
Here, deep sequencing is used to identify the mRNAs resident in the synaptic neuropil in the hippocampus. Analysis of a neuropil data set yields a list of 8,379 transcripts of which 2,550 are localised in dendrites and/or axons. Using a fluorescent barcode strategy to label individual mRNAs shows that the relative abundance of different mRNAs in the neuropil varies over 5 orders of magnitude. High-resolution in situ hybridisation validated the presence of mRNAs in both cultured neurons and hippocampal slices. Among the many mRNAs identified, a large fraction of known synaptic proteins including signaling molecules, scaffolds and receptors is discovered. These results reveal a previously unappreciated enormous potential for the local protein synthesis machinery to supply, maintain and modify the dendritic and synaptic proteome.
Using advances in library preparation for next generation sequencing experiments, the diversity of 3’UTR isoforms present in localised transcripts from the rat hippocampus is examined. The obtained results indicate that there is an increase in 3’UTR heterogeneity and 3’UTR length in neuronal tissue. The evolutionary importance of the 3’UTR diversity and correlation with changes in species,tissue and cell complexity is investigated. The conducted analysis reveals the population of 3’UTR isoforms required for transcript localisation in overall neuronal transcriptome as well as the regulatory elements and binding sites specific for neuronal compartments. The configuration of poly(A) signals is correlated with gene function and can be further exploit to determine similar mechanisms for alternative polyadenylation.
Usage of custom specified methods for next-generation sequencing as well as novel approaches for RNA quantification and visualisation necessitate the development and implementation of new downstream analytic methods. Library methods for data-mining transcripts annotation, expression and ontology relations is provided. Usage of a specialised search engine targeting key features of previous experiments is proposed. A processing pipeline for NanoString technology, defining experimental quality and exploiting methods for data normalisation is developed. High-resolution in situ images are analysed by custom application, showing a correlation between RNA quantity and spatial distribution. The vast variety of bioinformatic methods included in this work indicates the importance of downstream analysis to reach biological conclusions. Maintaining the integrability and modularity of our implementations is of great priority, as the dynamic nature of many experimental techniques requires constant improvement in computational analysis.
Background: Health-related and disease-specific quality of life (HRQoL) has been increasingly valued as relevant clinical parameter in cystic fibrosis (CF) clinical care and clinical trials. HRQoL measures should assess – among other domains – daily functioning from a patient’s perspective. However, validation studies for the most frequently used HRQoL questionnaire in CF, the Cystic Fibrosis Questionnaire (CFQ), have not included measures of physical activity or fitness. The objective of this study was, therefore, to determine the cross-sectional and longitudinal relationships between HRQoL, physical activity and fitness in patients with CF.
Methods: Baseline (n = 76) and 6-month follow-up data (n = 70) from patients with CF (age ≥12 years, FEV1 ≥35%) were analysed. Patients participated in two multi-centre exercise intervention studies with identical assessment methodology. Outcome variables included HRQoL (German revised multi-dimensional disease-specific CFQ (CFQ-R)), body composition, pulmonary function, physical activity, short-term muscle power, and aerobic fitness by peak oxygen uptake and aerobic power.
Results: Peak oxygen uptake was positively related to 7 of 13 HRQoL scales cross-sectionally (r = 0.30-0.46). Muscle power (r = 0.25-0.32) and peak aerobic power (r = 0.24-0.35) were positively related to 4 scales each, and reported physical activity to 1 scale (r = 0.29). Changes in HRQoL-scores were directly and significantly related to changes in reported activity (r = 0.35-0.39), peak aerobic power (r = 0.31-0.34), and peak oxygen uptake (r = 0.26-0.37) in 3 scales each. Established associates of HRQoL such as FEV1 or body mass index correlated positively with fewer scales (all 0.24 < r < 0.55).
Conclusions: HRQoL was associated with physical fitness, especially aerobic fitness, and to a lesser extent with reported physical activity. These findings underline the importance of physical fitness for HRQoL in CF and provide an additional rationale for exercise testing in this population.
Trial registration: ClinicalTrials.gov, NCT00231686
This note offers reflections on qualified market access (QMA) - the practice of linking trade agreements to values such as human rights, labour standards, or environmental protection. This idea has been suggested by political theorists as a way of fulfilling our duties to the global poor and of making the global economic system more just, and it has influenced a number of concrete policies, such as European Union (EU) trade policies. Yet, in order to assess its merits tout court, different perspectives and disciplines need to be brought together, such as international law, economics, political science, and philosophy. It is also worth reflecting on existing practices, such as those of the EU. This note summarises some insights about QMA by drawing such research together and considers the areas in which further research is needed, whilst reflecting also on the merits of interdisciplinary exchanges on such topics.