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The glomerulosclerosis gene Mpv17 encodes a peroxisomal protein producing reactive oxygen species
(1994)
RNA is one of the most important molecules in living organisms. One of its main functions is to regulate gene expression. This involves binding to and forming a joint structure with a messenger RNA. An RNAs functions is determined by its sequence and the structure it folds into. Accordingly, the prediction of individual as well as joint structures is an important area of research. In this thesis a method for the prediction of RNA-RNA joint structure using their minimum free energy (mfe) structures was developed. It is able to extensively explore the joint structural landscape of two interacting RNAs by taking advantage of the locality of changes in the RNAs structures as well as natural and energetic constraints. The method predicts the mfe joint structure as well as alternative stable joint structures while also computing non-optimal folding pathways from the unbound individual mfe structures to the predicted joint structures. It is shown how an enumeration approach is used which is able to deal with the enormous search space as well as to avoid any cyclic behaviour. The method is evaluated using two standard datasets of known interacting RNAs and shows good results.
MOTIVATION: The genome projects produce a wealth of protein sequences. Theoretical methods to predict possible structures and functions are needed for screening purposes, large-scale comparisons and in-depth analysis to identify worthwhile targets for further experimental research. Sequence-structure alignment is a basic tool for the identification of model folds for protein sequences and the construction of crude structural models. Empirical contact potentials (potentials of mean force) are used to optimize and evaluate such alignments. RESULTS: We propose new scoring schemes based on a contact definition derived from Voronoi decompositions of the three-dimensional coordinates of protein structures. We demonstrate that Voronoi potentials are superior to pure distance-based contact potentials with respect to recognition rate and significance for native folds. Moreover, the scoring scheme has the potential to provide a reasonable balance of detail and ion such that it is also useful for the recognition of distantly related (both homologous and non-homologous) proteins. This is demonstrated here on a set of structural alignments showing much better correspondence of native and model scores for the Voronoi potentials as compared to conventional distance-based potentials.
Scientific or statistical research has long been the domain of dedicated programming languages such as R, SPSS or SAS. A few years other competitors entered the arena, among them Python with its powerful SciPy package. The following article introduces SciPy by applying a small subset of its functionality to a well-known dataset.
Recently, we discovered a cholinergic mechanism that inhibits the adenosine triphosphate (ATP)-dependent release of interleukin-1 beta (IL-1 beta) by human monocytes via nicotinic acetylcholine receptors (nAChRs) composed of alpha 7, alpha 9 and/or alpha 10 subunits. Furthermore, we identified phosphocholine (PC) and dipalmitoylphosphatidylcholine (DPPC) as novel nicotinic agonists that elicit metabotropic activity at monocytic nAChR. Interestingly, PC does not provoke ion channel responses at conventional nAChRs composed of subunits alpha 9 and alpha 10. The purpose of this study is to determine the composition of nAChRs necessary for nicotinic signaling in monocytic cells and to test the hypothesis that common metabolites of phosphatidylcholines, lysophosphatidylcholine (LPC) and glycerophosphocholine (G-PC), function as nAChR agonists. In peripheral blood mononuclear cells from nAChR gene-deficient mice, we demonstrated that inhibition of ATP-dependent release of IL-1 beta by acetylcholine (ACh), nicotine and PC depends on subunits alpha 7, alpha 9 and alpha 10. Using a panel of nAChR antagonists and siRNA technology, we confirmed the involvement of these subunits in the control of IL-1 beta release in the human monocytic cell line U937. Furthermore, we showed that LPC (C16:0) and G-PC efficiently inhibit ATP-dependent release of IL-1 beta. Of note, the inhibitory effects mediated by LPC and G-PC depend on nAChR subunits alpha 9 and alpha 10, but only to a small degree on alpha 7. In Xenopus laevis oocytes heterologously expressing different combinations of human alpha 7, alpha 9 or alpha 10 subunits, ACh induced canonical ion channel activity, whereas LPC, G-PC and PC did not. In conclusion, we demonstrate that canonical nicotinic agonists and PC elicit metabotropic nAChR activity in monocytes via interaction of nAChR subunits alpha 7, alpha 9 and alpha 10. For the metabotropic signaling of LPC and G-PC, nAChR subunits alpha 9 and alpha 10 are needed, whereas alpha 7 is virtually dispensable. Furthermore, molecules bearing a PC group in general seem to regulate immune functions without perturbing canonical ion channel functions of nAChR.
A framework of decision‐support systems in advanced manufacturing enterprises ‐ a systems view
(1997)
Helping Johnny to Analyze Malware: A Usability-Optimized Decompiler and Malware Analysis User Study
(2016)
The dawn of the 21st Century has witnessed a tremendous increase in trade pacts among nations, resulting in renewed hopes for sustainable enterprise development in emerging economies worldwide. Ghana and other sub- Saharan African (SSA) countries have signed onto several North-South and South-South free trade agreements with the hope of strengthening their presence in the international trade arena, and to promote economic growth in SSA. For over two decades, however, very little has changed, and many have dashed their high hopes as enterprises continue to struggle in SSA. Not even the African Continental Free Trade Agreement (AfCFTA) could renew the hopes of sceptics. Several studies opined that enterprises in SSA could improve their domestic and international competitiveness by establishing mutually beneficial partnerships with their counterparts from the Global North and South. This study delved into the issues that affect North-South and South-South business collaborations and recommends key success factors that could help promote mutually beneficial cross-border business partnerships. The research includes both literature and empirical information on the key success factors of business partnerships between African enterprises as well as between African enterprises and firms from the Global North. We approached the study qualitatively using a phenomenological research design. Research participants included important stakeholders in Africa and Europe's international trade and sustainable enterprise development ecosystem. The study identified several challenges with the current business collaborations and recommended new ways of making such partnerships more beneficial.