motifDiverge: a model for assessing the statistical significance of gene regulatory motif divergence between two DNA sequences

Next-generation sequencing technology enables the identification of thousands of gene regulatory sequences in many cell types and organisms. We consider the problem of testing if two such sequences differ in their number of binding site motifs for a given transcription factor (TF) protein. Binding site motifs impart regulatory function by providing TFs the opportunity to bind to genomic elements and thereby affect the expression of nearby genes. Evolutionary changes to such functional DNA are hypothesized to be major contributors to phenotypic diversity within and between species; but despite the importance of TF motifs for gene expression, no method exists to test for motif loss or gain. Assuming that motif counts are Binomially distributed, and allowing for dependencies between motif instances in evolutionarily related sequences, we derive the probability mass function of the difference in motif counts between two nucleotide sequences. We provide a method to numerically estimate this distribution from genomic data and show through simulations that our estimator is accurate. Finally, we introduce the R package {\tt motifDiverge} that implements our methodology and illustrate its application to gene regulatory enhancers identified by a mouse developmental time course experiment. While this study was motivated by analysis of regulatory motifs, our results can be applied to any problem involving two correlated Bernoulli trials

TRUST MANAGEMENT – AN INFORMATION SYSTEMS PERSPECTIVE

The focus of the Information Systems (IS) research on trust has been on the perception of trust and explaining the concept in terms of its antecedents. The merits of this descriptive and explanatory knowledge notwithstanding, the usefulness and applicability of this knowledge for organizations that aim at actively influencing their trust position is limited. In light of recent public scandals in areas such as social media, car manufacturing or financial services, organizations require an understanding of how customer trust can be managed using contemporary information systems solutions. In this paper we propose trust management as an IS theme of increasing relevance and draw upon extant research in IS, psychology, and marketing to bridge the gap between topics such as risk management, compliance management and governance on the one hand and trust management on the other. We utilize Botsman’s concept of uncertainty as a proxy for customer trust to bring together organizational approaches that can objectively reduce uncertainty linked to an organization, its processes, products, and services with the customer’s perception of this uncertainty. We contribute to the further maturity of trust management by providing new foundations and providing explicit advice on how to improve trust in organizations

Alternative glues for the production of ATLAS silicon strip modules for the Phase-II upgrade of the ATLAS Inner Detector

The Phase-II upgrade of the ATLAS detector for the High Luminosity Large Hadron Collider (HL-LHC) includes the replacement of the current Inner Detector with an all-silicon tracker consisting of pixel and strip detectors. The current Phase-II detector layout requires the construction of 20,000 strip detector modules consisting of sensor, circuit boards and readout chips, which are connected mechanically using adhesives. The adhesive between readout chips and circuit board is a silver epoxy glue as was used in the current ATLAS SemiConductor Tracker (SCT). This glue has several disadvantages, which motivated the search for an alternative. This paper presents a study concerning the use of six ultra-violet (UV) cure glues and a glue pad for use in the assembly of silicon strip detector modules for the ATLAS upgrade. Trials were carried out to determine the ease of use, the thermal conduction and shear strength, thermal cycling, radiation hardness, corrosion resistance and shear strength tests. These investigations led to the exclusion of three UV cure glues as well as the glue pad. Three UV cure glues were found to be possible better alternatives. Results from electrical tests of first prototype modules constructed using these glues are presented.Comment: 23 pages, to be published in Journal of Instrumentatio

Interference of Clocks: A Quantum Twin Paradox

The phase of matter waves depends on proper time and is therefore susceptible to special-relativistic (kinematic) and gravitational time dilation (redshift). Hence, it is conceivable that atom interferometers measure general-relativistic time-dilation effects. In contrast to this intuition, we show that light-pulse interferometers without internal transitions are not sensitive to gravitational time dilation, whereas they can constitute a quantum version of the special-relativistic twin paradox. We propose an interferometer geometry isolating the effect that can be used for quantum-clock interferometry.Comment: 9 Pages, 2 Figure

Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAP

Inserted (I) domains function as ligand-binding domains in adhesins that support cell adhesion and migration in many eukaryotic phyla. These adhesins include integrin alpha beta heterodimers in metazoans and single subunit transmembrane proteins in apicomplexans such as TRAP in Plasmodium and MIC2 in Toxoplasma. Here we show that the I domain of TRAP is essential for sporozoite gliding motility, mosquito salivary gland invasion and mouse infection. Its replacement with the I domain from Toxoplasma MIC2 fully restores tissue invasion and parasite transmission, while replacement with the aXI domain from human integrins still partially restores liver infection. Mutations around the ligand binding site allowed salivary gland invasion but led to inefficient transmission to the rodent host. These results suggest that apicomplexan parasites appropriated polyspecific I domains in part for their ability to engage with multiple ligands and to provide traction for emigration into diverse organs in distant phyla

Atom-interferometric test of the universality of gravitational redshift and free fall

Light-pulse atom interferometers constitute powerful quantum sensors for inertial forces. They are based on delocalised spatial superpositions and the combination with internal transitions directly links them to atomic clocks. Since classical tests of the gravitational redshift are based on a comparison of two clocks localised at different positions under gravity, it is promising to explore whether the aforementioned interferometers constitute a competitive alternative for tests of general relativity. Here we present a specific geometry which together with state transitions leads to a scheme that is concurrently sensitive to both violations of the universality of free fall and gravitational redshift, two premises of general relativity. The proposed interferometer does not rely on a superposition of internal states, but merely on transitions between them, and therefore generalises the concept of physical atomic clocks and quantum-clock interferometry. An experimental realisation seems feasible with already demonstrated techniques in state-of-the-art facilities.Comment: 8 pages, 4 figure