Honeycomb: android App of goal and task management for increased productivity

Treball final de Grau en Disseny i Desenvolupament de Videojocs. Codi: VJ1241. Curs acadèmic: 2019/2020Too much time is wasted blindly following the river of life with no clear direction in sight. This project is made for those who always seek to have more than what they have. This is my first opportunity to create something truly helpful for many people that are struggling to find the motivation to follow though their commitments and achieve greater heights. This app, Honeycomb, helps put the control of the user’s life in its hands by allowing him or her to create a massive action plan for the future and committing to it through constant action and planning. Honeycomb is developed by me, Arthur Knegtel, and this document represents my Final Degree Work on the Bachelor’s Degree in Video Game Design and Development

Constructing the Sublime: The Discourse on Architecture and Louis XIV's Sublimity in Seventeenth-Century Paris

In 1686, the French Jesuit and writer René Rapin wrote his treatise Du grand ou du sublime, in which he proclaimed French king Louis XIV as being the most sublime person. To do this, he used the concept of 'le sublime', a notion Rapin derived from the Greek classical writer Longinus. With his book, Rapin actually builds on an older tradition: writers had been using an elevated rhetoric to write about Louis XIV for many decades. In this discourse, architecture played a key factor. Writers recognized the overwhelming potential of the king's buildings and future projects, and also employed architectural metaphors and transcendent fictions to try and elevate the monarch. Ultimately, however, all of these works and projects - like Rapin's claim - proved very problematic. Firstly, the rhetoric of the sublime used to evoke the effect of sublimity has always been problematic, since it relies on an interplay between opposite extremes, which are highly unstable. Secondly, when attempting to establish the king himself as sublime, writers were confronted with the far-reaching implications of this claim. The sublime is not only an extreme notion but also a highly subjective one. It cannot be asserted, nor can it be wielded.Medieval and Early Modern Studie

Enquête beek(dal)herstelprojecten 2004-2008 : evaluatie van beekherstel over de periode 1960-2008 en analyse van effecten van 9 voorbeeldprojecten

Om inzicht te krijgen in de stand van de aquatisch-ecologische aspecten van beekherstel zijn door Alterra in de jaren 1993 (uitgebreid), 1998 (verkort) en 2003 (verkort) beekherstelenquêtes uitgevoerd en gerapporteerd. De Nederlandse natuur- en waterbeheerders hebben behoefte aan de resultaten van dergelijke enquêtes om (1) van elkaar te leren en (2) om nieuwe inzichten en mogelijkheden te leren kennen. OBN heeft de resultaten nodig om een scherp beeld van de mogelijkheden en onmogelijkheden van verschillende herstelmaatregelen onder verschillende omstandigheden te krijgen. In 2008 is een opnieuw een enquête gehouden, welke een vervolg is op de voorgaande beekherstelenquêtes. Deze laatste enquête echter richtte zich naast beekherstel ook op beekdalherstel. In dit rapport wordt de actuele stand (2004-2008) omtrent beek(dal)herstel in Nederland gerapporteerd. (zie ook Alterra rapport 1858)

Engineering of Cyclodextrin Product Specificity and pH Optima of the Thermostable Cyclodextrin Glycosyltransferase from Thermoanaerobacterium thermosulfurigenes EM1

The product specificity and pH optimum of the thermostable cyclodextrin glycosyltransferase (CGTase) from Thermoanaerobacterium thermosulfurigenes EM1 was engineered using a combination of x-ray crystallography and site-directed mutagenesis. Previously, a crystal soaking experiment with the Bacillus circulans strain 251 β-CGTase had revealed a maltononaose inhibitor bound to the enzyme in an extended conformation. An identical experiment with the CGTase from T. thermosulfurigenes EM1 resulted in a 2.6-Å resolution x-ray structure of a complex with a maltohexaose inhibitor, bound in a different conformation. We hypothesize that the new maltohexaose conformation is related to the enhanced α-cyclodextrin production of the CGTase. The detailed structural information subsequently allowed engineering of the cyclodextrin product specificity of the CGTase from T. thermosulfurigenes EM1 by site-directed mutagenesis. Mutation D371R was aimed at hindering the maltohexaose conformation and resulted in enhanced production of larger size cyclodextrins (β- and γ-CD). Mutation D197H was aimed at stabilization of the new maltohexaose conformation and resulted in increased production of α-CD. Glu258 is involved in catalysis in CGTases as well as α-amylases, and is the proton donor in the first step of the cyclization reaction. Amino acids close to Glu258 in the CGTase from T. thermosulfurigenes EM1 were changed. Phe284 was replaced by Lys and Asn327 by Asp. The mutants showed changes in both the high and low pH slopes of the optimum curve for cyclization and hydrolysis when compared with the wild-type enzyme. This suggests that the pH optimum curve of CGTase is determined only by residue Glu258.

From Nonspecific DNA–Protein Encounter Complexes to the Prediction of DNA–Protein Interactions

©2009 Gao, Skolnick. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.doi:10.1371/journal.pcbi.1000341DNA–protein interactions are involved in many essential biological activities. Because there is no simple mapping code between DNA base pairs and protein amino acids, the prediction of DNA–protein interactions is a challenging problem. Here, we present a novel computational approach for predicting DNA-binding protein residues and DNA–protein interaction modes without knowing its specific DNA target sequence. Given the structure of a DNA-binding protein, the method first generates an ensemble of complex structures obtained by rigid-body docking with a nonspecific canonical B-DNA. Representative models are subsequently selected through clustering and ranking by their DNA–protein interfacial energy. Analysis of these encounter complex models suggests that the recognition sites for specific DNA binding are usually favorable interaction sites for the nonspecific DNA probe and that nonspecific DNA–protein interaction modes exhibit some similarity to specific DNA–protein binding modes. Although the method requires as input the knowledge that the protein binds DNA, in benchmark tests, it achieves better performance in identifying DNA-binding sites than three previously established methods, which are based on sophisticated machine-learning techniques. We further apply our method to protein structures predicted through modeling and demonstrate that our method performs satisfactorily on protein models whose root-mean-square Ca deviation from native is up to 5 Å from their native structures. This study provides valuable structural insights into how a specific DNA-binding protein interacts with a nonspecific DNA sequence. The similarity between the specific DNA–protein interaction mode and nonspecific interaction modes may reflect an important sampling step in search of its specific DNA targets by a DNA-binding protein

Rational Mutagenesis of Cyclodextrin Glucanotransferase at the Calcium Binding Regions for Enhancement of Thermostability

Studies related to the engineering of calcium binding sites of CGTase are limited. The calcium binding regions that are known for thermostability function were subjected to site-directed mutagenesis in this study. The starting gene-protein is a variant of CGTase Bacillus sp. G1, reported earlier and denoted as “parent CGTase” herein. Four CGTase variants (S182G, S182E, N132R and N28R) were constructed. The two variants with a mutation at residue 182, located adjacent to the Ca-I site and the active site cleft, possessed an enhanced thermostability characteristic. The activity half-life of variant S182G at 60 °C was increased to 94 min, while the parent CGTase was only 22 min. This improvement may be attributed to the formation of a shorter α-helix and the alleviation of unfavorable steric strains by glycine at the corresponding region. For the variant S182E, an extra ionic interaction at the A/B domain interface increased the half-life to 31 min, yet it reduced CGTase activity. The introduction of an ionic interaction at the Ca-I site via the mutation N132R disrupted CGTase catalytic activity. Conversely, the variant N28R, which has an additional ionic interaction at the Ca-II site, displayed increased cyclization activity. However, thermostability was not affected

DNA-Induced Unfolding of the Thyroid Hormone Receptor a A/B Domain through Allostery

The A/B domains of nuclear receptors such as thyroid receptor a (TRa) are considered to be conformationally flexible and can potentially adopt multiple structural conformations. We used intrinsic tryptophan fluorescence quenching and circular dichroism spectroscopy to characterize the unfolding of this A/B domain upon DNA binding to the contiguous DNA binding domain (DBD). We propose that this allosteric change in A/B domain conformation can allow it to make the multiple interactions with distinct molecular factors of the transcriptional preinitiation complex. We further suggest that by influencing the affinity of the DBD for DNA, A/B domain can fine-tune the recognition of promotor DNA by TRa

recA mediated spontaneous deletions of the icaADBC operon of clinical Staphylococcus epidermidis isolates: a new mechanism of phenotypic variations

Phenotypic variation of Staphylococcus epidermidis involving the slime related ica operon results in heterogeneity in surface characteristics of individual bacteria in axenic cultures. Five clinical S. epidermidis isolates demonstrated phenotypic variation, i.e. both black and red colonies on Congo Red agar. Black colonies displayed bi-modal electrophoretic mobility distributions at pH 2, but such phenotypic variation was absent in red colonies of the same strain as well as in control strains without phenotypic variation. All red colonies had lost ica and the ability to form biofilms, in contrast to black colonies of the same strain. Real time PCR targeting icaA indicated a reduction in gene copy number within cultures exhibiting phenotypic variation, which correlated with phenotypic variations in biofilm formation and electrophoretic mobility distribution of cells within a culture. Loss of ica was irreversible and independent of the mobile element IS256. Instead, in high frequency switching strains, spontaneous mutations in lexA were found which resulted in deregulation of recA expression, as shown by real time PCR. RecA is involved in genetic deletions and rearrangements and we postulate a model representing a new mechanism of phenotypic variation in clinical isolates of S. epidermidis. This is the first report of S. epidermidis strains irreversibly switching from biofilm-positive to biofilm-negative phenotype by spontaneous deletion of icaADBC