Intermezzo in Dust

Y OUR breath comes in short, quick gasps. Your tongue feels dry and swollen as you monotonously explore each crack and crevice of your mouth-your teeth are harsh and rough and the irritating coat of dirt on their edges will not come off..

The Contribution of Customer Relationship Management to Sales Performance in the Hotel Business

Elektroniskā versija nesatur pielikumusTirgvedība ir tik sarežģīta joma, ka Vannameikers (Wannamaker, miris 1922. gadā) teicis sekojošo: „Es zinu, ka puse no maniem reklamēšanās izdevumiem ir naudas izšķiešana, es tikai nezinu, kura puse tā ir.”1 Šķiet, ka daudz nekas nav mainījies. Saskaņā ar 2012. gada McKinsey un OWM pētījumu, tikai 15% no atbildīgajiem mārketinga vadītājiem tic, ka viņi zina, kāds ir dažādu komunikācijas kanālu ieguldījums uzņēmuma veiksmē. Aģentūras savu klientu kompetenci vērtē daudz zemāk, viņuprāt, tikai 3% piemīt šī spēja.2 Promocijas darba mērķis ir novērtēt vistipiskāko tiešo mārketinga kanālu un komunikācijas biežuma ietekmi uz atkārtotu pirkuma veikšanu, t.i. uz esošo viesnīcas klientu lojalitāti luksus klases viesnīcu segmentā klientu attiecību vadības (CRM) kontekstā. Sarežģītajā CRM jēdzienā mārketinga komunikācija spēlē galveno lomu, radot atcerēšanos un rosinot rezervēšanas impulsus, bet līdz šim nav ticis izvērtēts ne jautājums par lietderīgu komunikācijas biežumu, ne abu dažādo mediju kanālu kā vēsts pārnesēja kvalitāti CRM. Lai atbildētu uz šiem jautājumiem, četru Vācijas pieczvaigžņu viesnīcu mārketinga aktivitātes un vēsts saņēmēju rezervēšanas uzvedība tika mērīta un analizēta 4,5 gadu periodā. „Lielo Datu” vidē un integrētas CRM sistēmas lietošanā pirmo reizi bija iespējams veikt ilgstošu pētījumu par komunikācijas ietekmi uz lojalitāti. Līdz šim visi pētījumi ir novērtējuši tikai īstermiņa ietekmi uz komunikācijas darbībām pārdošanā, bet neuzsvēra komunikācijas vērtību ilgtermiņā, lai radītu luksus klases viesnīcu segmenta klientu lojalitāti. Promocijas darba rezultāts ir ECSI lojalitātes modeļa uzlabošana ar tādiem mainīgajiem kā komunikācijas kanāls, biežums un laiks. Uz diskusiju zinātniskajās aprindās par to, kura atbildes funkcija vislabāk apraksta komunikācijas rezultātu CRM, var atbildēt ar lejupslīdošu līknes vienādojumu. Ar regresijas modeļa palīdzību ir izveidota formula, kas ļauj aprēķināt efektīvu komunikācijas biežumu kanālā. Pētījuma rezultāti palīdz izveidot lietderīgu attiecību mārketinga (RM) stratēģiju, lai radītu pozitīvus rezultātus. Atslēgas vārdi: CRM, komunikācijas biežums, kanāla kvalitāte, lojalitāte, viesnīcu biznessMarketing is such a complex field that Wannamaker (died 1922) made the following famous statement: „I know that half of my advertising spending is wasted, I just don‘t know which half.”1 It seems that not much has changed. According to a 2012 study from McKinsey and OWM only 15% of the responsible marketing managers believe that they know how much the different communication channels contribute to the company’s success. Agencies rate the competence of their clients much lower, only 3% are considered to have this capability.2 The aim of this dissertation is to evaluate the influence of the most common direct marketing channels in the hotel business (e-mail and post mail) and the communication frequency on the re-buying behavior, i.e. the behavioral loyalty of existing hotel customers within a Customer Relationship Management context. Within the complex construct of CRM, marketing communication plays a central role in creating remembering effects and in initiating booking impulses, but neither the question of a worthwhile frequency nor the quality of the two different media channels as a message transmitter within CRM have been evaluated so far. In order to answer these questions the marketing activities of four five-star hotels in Germany and the booking behavior of the message recipients were measured and analyzed over a period of 4.5 years. Within a “Big Data” environment and the usage of an integrated CRM system, it was for the first time possible to carry out a long-time study about the effects of communication on loyalty. All studies so far evaluated only the short-term effects of communication actions on sales but did not focus on the value of communication over time for creating loyalty for hotel guests in the luxury hotel segment. The promotion work has resulted in an enhancement of the ECSI loyalty model by the variables communication channel, frequency and time. The discussion within the scientific community which response function best describes the results of communication within CRM could be answered by a concave downward equation. With the help of a regression model, a formula has been developed which helps to calculate an effective communication frequency per channel. The findings help to create a worthwhile relationship marketing (RM) strategy to generate positive results. Key words: CRM, communication frequency, channel quality, loyalty, hotel business

FACT – a framework for the functional interpretation of high-throughput experiments

BACKGROUND: Interpreting the results of high-throughput experiments, such as those obtained from DNA-microarrays, is an often time-consuming task due to the high number of data-points that need to be analyzed in parallel. It is usually a matter of extensive testing and unknown beforehand, which of the possible approaches for the functional analysis will be the most informative RESULTS: To address this problem, we have developed the Flexible Annotation and Correlation Tool (FACT). FACT allows for detection of important patterns in large data sets by simplifying the integration of heterogeneous data sources and the subsequent application of different algorithms for statistical evaluation or visualization of the annotated data. The system is constantly extended to include additional annotation data and comparison methods. CONCLUSION: FACT serves as a highly flexible framework for the explorative analysis of large genomic and proteomic result sets. The program can be used online; open source code and supplementary information are available at

Spin Wave Diffraction and Perfect Imaging of a Grating

We study the diffraction of Damon-Eshbach-type spin waves incident on a one-dimensional grating realized by micro slits in a thin permalloy film. By means of time-resolved scanning Kerr microscopy we observe unique diffraction patterns behind the grating which exhibit replications of the spin-wave field at the slits. We show that these spin-wave images, with details finer than the wavelength of the incident Damon-Eshbach spin wavelength, arise from the strongly anisotropic spin wave dispersion.Comment: 5 pages, 3 figure

The Gene Ontology of eukaryotic cilia and flagella.

BACKGROUND: Recent research into ciliary structure and function provides important insights into inherited diseases termed ciliopathies and other cilia-related disorders. This wealth of knowledge needs to be translated into a computational representation to be fully exploitable by the research community. To this end, members of the Gene Ontology (GO) and SYSCILIA Consortia have worked together to improve representation of ciliary substructures and processes in GO. METHODS: Members of the SYSCILIA and Gene Ontology Consortia suggested additions and changes to GO, to reflect new knowledge in the field. The project initially aimed to improve coverage of ciliary parts, and was then broadened to cilia-related biological processes. Discussions were documented in a public tracker. We engaged the broader cilia community via direct consultation and by referring to the literature. Ontology updates were implemented via ontology editing tools. RESULTS: So far, we have created or modified 127 GO terms representing parts and processes related to eukaryotic cilia/flagella or prokaryotic flagella. A growing number of biological pathways are known to involve cilia, and we continue to incorporate this knowledge in GO. The resulting expansion in GO allows more precise representation of experimentally derived knowledge, and SYSCILIA and GO biocurators have created 199 annotations to 50 human ciliary proteins. The revised ontology was also used to curate mouse proteins in a collaborative project. The revised GO and annotations, used in comparative 'before and after' analyses of representative ciliary datasets, improve enrichment results significantly. CONCLUSIONS: Our work has resulted in a broader and deeper coverage of ciliary composition and function. These improvements in ontology and protein annotation will benefit all users of GO enrichment analysis tools, as well as the ciliary research community, in areas ranging from microscopy image annotation to interpretation of high-throughput studies. We welcome feedback to further enhance the representation of cilia biology in GO

Structural and functional analysis of the MutS C-terminal tetramerization domain

The Escherichia coli DNA mismatch repair (MMR) protein MutS is essential for the correction of DNA replication errors. In vitro, MutS exists in a dimer/tetramer equilibrium that is converted into a monomer/dimer equilibrium upon deletion of the C-terminal 53 amino acids. In vivo and in vitro data have shown that this C-terminal domain (CTD, residues 801–853) is critical for tetramerization and the function of MutS in MMR and anti-recombination. We report the expression, purification and analysis of the E.coli MutS-CTD. Secondary structure prediction and circular dichroism suggest that the CTD is folded, with an α-helical content of 30%. Based on sedimentation equilibrium and velocity analyses, MutS-CTD forms a tetramer of asymmetric shape. A single point mutation (D835R) abolishes tetramerization but not dimerization of both MutS-CTD and full-length MutS. Interestingly, the in vivo and in vitro MMR activity of MutS(CF/D835R) is diminished to a similar extent as a truncated MutS variant (MutS800, residues 1–800), which lacks the CTD. Moreover, the dimer-forming MutS(CF/D835R) has comparable DNA binding affinity with the tetramer-forming MutS, but is impaired in mismatch-dependent activation of MutH. Our data support the hypothesis that tetramerization of MutS is important but not essential for MutS function in MMR

ELM—the database of eukaryotic linear motifs

Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instance

Elastic SCAD as a novel penalization method for SVM classification tasks in high-dimensional data

<p>Abstract</p> <p>Background</p> <p>Classification and variable selection play an important role in knowledge discovery in high-dimensional data. Although Support Vector Machine (SVM) algorithms are among the most powerful classification and prediction methods with a wide range of scientific applications, the SVM does not include automatic feature selection and therefore a number of feature selection procedures have been developed. Regularisation approaches extend SVM to a feature selection method in a flexible way using penalty functions like LASSO, SCAD and Elastic Net.</p> <p>We propose a novel penalty function for SVM classification tasks, Elastic SCAD, a combination of SCAD and ridge penalties which overcomes the limitations of each penalty alone.</p> <p>Since SVM models are extremely sensitive to the choice of tuning parameters, we adopted an interval search algorithm, which in comparison to a fixed grid search finds rapidly and more precisely a global optimal solution.</p> <p>Results</p> <p>Feature selection methods with combined penalties (Elastic Net and Elastic SCAD SVMs) are more robust to a change of the model complexity than methods using single penalties. Our simulation study showed that Elastic SCAD SVM outperformed LASSO (<it>L</it>₁) and SCAD SVMs. Moreover, Elastic SCAD SVM provided sparser classifiers in terms of median number of features selected than Elastic Net SVM and often better predicted than Elastic Net in terms of misclassification error.</p> <p>Finally, we applied the penalization methods described above on four publicly available breast cancer data sets. Elastic SCAD SVM was the only method providing robust classifiers in sparse and non-sparse situations.</p> <p>Conclusions</p> <p>The proposed Elastic SCAD SVM algorithm provides the advantages of the SCAD penalty and at the same time avoids sparsity limitations for non-sparse data. We were first to demonstrate that the integration of the interval search algorithm and penalized SVM classification techniques provides fast solutions on the optimization of tuning parameters.</p> <p>The penalized SVM classification algorithms as well as fixed grid and interval search for finding appropriate tuning parameters were implemented in our freely available R package 'penalizedSVM'.</p> <p>We conclude that the Elastic SCAD SVM is a flexible and robust tool for classification and feature selection tasks for high-dimensional data such as microarray data sets.</p

Single-molecule multiparameter fluorescence spectroscopy reveals directional MutS binding to mismatched bases in DNA

Mismatch repair (MMR) corrects replication errors such as mismatched bases and loops in DNA. The evolutionarily conserved dimeric MMR protein MutS recognizes mismatches by stacking a phenylalanine of one subunit against one base of the mismatched pair. In all crystal structures of G:T mismatch-bound MutS, phenylalanine is stacked against thymine. To explore whether these structures reflect directional mismatch recognition by MutS, we monitored the orientation of Escherichia coli MutS binding to mismatches by FRET and anisotropy with steady state, pre-steady state and single-molecule multiparameter fluorescence measurements in a solution. The results confirm that specifically bound MutS bends DNA at the mismatch. We found additional MutS–mismatch complexes with distinct conformations that may have functional relevance in MMR. The analysis of individual binding events reveal significant bias in MutS orientation on asymmetric mismatches (G:T versus T:G, A:C versus C:A), but not on symmetric mismatches (G:G). When MutS is blocked from binding a mismatch in the preferred orientation by positioning asymmetric mismatches near the ends of linear DNA substrates, its ability to authorize subsequent steps of MMR, such as MutH endonuclease activation, is almost abolished. These findings shed light on prerequisites for MutS interactions with other MMR proteins for repairing the appropriate DNA strand

Mutations in the MutSα interaction interface of MLH1 can abolish DNA mismatch repair

MutLα, a heterodimer of MLH1 and PMS2, plays a central role in human DNA mismatch repair. It interacts ATP-dependently with the mismatch detector MutSα and assembles and controls further repair enzymes. We tested if the interaction of MutLα with DNA-bound MutSα is impaired by cancer-associated mutations in MLH1, and identified one mutation (Ala128Pro) which abolished interaction as well as mismatch repair activity. Further examinations revealed three more residues whose mutation interfered with interaction. Homology modelling of MLH1 showed that all residues clustered in a small accessible surface patch, suggesting that the major interaction interface of MutLα for MutSα is located on the edge of an extensive β-sheet that backs the MLH1 ATP binding pocket. Bioinformatic analysis confirmed that this patch corresponds to a conserved potential protein–protein interaction interface which is present in both human MLH1 and its E.coli homologue MutL. MutL could be site-specifically crosslinked to MutS from this patch, confirming that the bacterial MutL–MutS complex is established by the corresponding interface in MutL. This is the first study that identifies the conserved major MutLα–MutSα interaction interface in MLH1 and demonstrates that mutations in this interface can affect interaction and mismatch repair, and thereby can also contribute to cancer development