Query processing of spatial objects: Complexity versus Redundancy

The management of complex spatial objects in applications, such as geography and cartography, imposes stringent new requirements on spatial database systems, in particular on efficient query processing. As shown before, the performance of spatial query processing can be improved by decomposing complex spatial objects into simple components. Up to now, only decomposition techniques generating a linear number of very simple components, e.g. triangles or trapezoids, have been considered. In this paper, we will investigate the natural trade-off between the complexity of the components and the redundancy, i.e. the number of components, with respect to its effect on efficient query processing. In particular, we present two new decomposition methods generating a better balance between the complexity and the number of components than previously known techniques. We compare these new decomposition methods to the traditional undecomposed representation as well as to the well-known decomposition into convex polygons with respect to their performance in spatial query processing. This comparison points out that for a wide range of query selectivity the new decomposition techniques clearly outperform both the undecomposed representation and the convex decomposition method. More important than the absolute gain in performance by a factor of up to an order of magnitude is the robust performance of our new decomposition techniques over the whole range of query selectivity

Contrasting heterozygosity-fitness correlations across life in a long-lived seabird

Selection is a central force underlying evolutionary change and can vary in strength and direction, for example across time and space. The fitness consequences of individual genetic diversity have often been investigated by testing for multilocus heterozygosity-fitness correlations (HFCs), but few studies have been able to assess HFCs across life stages and in both sexes. Here, we test for HFCs using a 26-year longitudinal individual-based data set from a large population of a long-lived seabird (the common tern, Sterna hirundo), where 7,974 chicks and breeders of known age were genotyped at 15 microsatellite loci and sampled for life-history traits over the complete life cycle. Heterozygosity was not correlated with fledging or post-fledging prospecting probabilities, but was positively correlated with recruitment probability. For breeders, annual survival was not correlated with heterozygosity, but annual fledgling production was negatively correlated with heterozygosity in males and highest in intermediately heterozygous females. The contrasting HFCs among life stages and sexes indicate differential selective processes and emphasize the importance of assessing fitness consequences of traits over complete life histories

Moving Beyond Noninformative Priors: Why and How to Choose Weakly Informative Priors in Bayesian Analyses

Throughout the last two decades, Bayesian statistical methods have proliferated throughout ecology and evolution. Numerous previous references established both philosophical and computational guidelines for implementing Bayesian methods. However, protocols for incorporating prior information, the defining characteristic of Bayesian philosophy, are nearly nonexistent in the ecological literature. Here, I hope to encourage the use of weakly informative priors in ecology and evolution by providing a ‘consumer\u27s guide’ to weakly informative priors. The first section outlines three reasons why ecologists should abandon noninformative priors: 1) common flat priors are not always noninformative, 2) noninformative priors provide the same result as simpler frequentist methods, and 3) noninformative priors suffer from the same high type I and type M error rates as frequentist methods. The second section provides a guide for implementing informative priors, wherein I detail convenient ‘reference’ prior distributions for common statistical models (i.e. regression, ANOVA, hierarchical models). I then use simulations to visually demonstrate how informative priors influence posterior parameter estimates. With the guidelines provided here, I hope to encourage the use of weakly informative priors for Bayesian analyses in ecology. Ecologists can and should debate the appropriate form of prior information, but should consider weakly informative priors as the new ‘default’ prior for any Bayesian model

Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients

Multicomponent solid forms of active pharmaceutical ingredients represent a modern method of tuning their physicochemical properties. Typically, salts are the most commonly used multicomponent solid form in the pharmaceutical industry. More than 38% are formulated as organic cations. Salt screening is an essential but demanding step when identifying the most appropriate formulation. The microbatch under-oil crystallization technique of proteins has been combined with the previously developed high-throughput vapour-diffusion screening for use as a novel method of primary salt screening of organic cations. The procedure allows the set up of about 100 crystallization experiments per 30 min. This requires between 17 and 564 mg of screened cationic active pharmaceutical ingredients, which were of moderate to very high water solublity. Five distinct organic salts, three of them diverse active pharmaceutical compounds or the other enantiomer thereof, in the form of chloride salts were tested. The screening was extremely successful; at least two new single-crystal structures could be obtained for each particular compound and many more salts as single crystals were formed compared with our previous vapour-diffusion method

High-frequency multimodal atomic force microscopy

Multifrequency atomic force microscopy imaging has been recently demonstrated as a powerful technique for quickly obtaining information about the mechanical properties of a sample. Combining this development with recent gains in imaging speed through small cantilevers holds the promise of a convenient, high-speed method for obtaining nanoscale topography as well as mechanical properties. Nevertheless, instrument bandwidth limitations on cantilever excitation and readout have restricted the ability of multifrequency techniques to fully benefit from small cantilevers. We present an approach for cantilever excitation and deflection readout with a bandwidth of 20 MHz, enabling multifrequency techniques extended beyond 2 MHz for obtaining materials contrast in liquid and air, as well as soft imaging of delicate biological samples

Measuring Novel Antecedents of Mental Illness: The Questionnaire of Unpredictability in Childhood

Increasing evidence indicates that, in addition to poverty, maternal depression, and other well-established factors, unpredictability of maternal and environmental signals early in life influences trajectories of brain development, determining risk for subsequent mental illness. However, whereas most risk factors for later vulnerability to mental illness are readily measured using existing, clinically available tools, there are no similar measures for assessing early-life unpredictability. Here we validate the Questionnaire of Unpredictability in Childhood (QUIC) and examine its associations with mental health in the context of other indicators of childhood adversity (e.g., traumatic life events, socioeconomic status, and parenting quality). The QUIC was initially validated through administration to a cohort of adult females (N = 116) and then further refined in two additional independent cohorts (male Veterans, N = 95, and male and female adolescents, N = 175). The QUIC demonstrated excellent internal (α = 0.89) and test–retest reliability (r = 92). Scores on the QUIC were positively correlated with other prospective indicators of exposures to unpredictable maternal inputs in infancy and childhood (unpredictable maternal mood and sensory signals), and accuracy of recall also was confirmed with prospective data. Importantly, the QUIC predicted symptoms of anxiety, depression, and anhedonia in the three study cohorts, and these effects persisted after adjusting for other previously established risk factors. The QUIC, a reliable and valid self-report assessment of exposure to unpredictability in the social, emotional, and physical domains during early life, is a brief, comprehensive, and promising instrument for predicting risk for mental illness

Rationale and Design of the Genetic Contribution to Drug Induced Renal Injury (DIRECT) Study

IntroductionNephrotoxicity from drugs accounts for 18% to 27% of cases of acute kidney injury. Determining a genetic predisposition may potentially be important in minimizing risk. The aims of this study are as follows: to determine whether a genetic predisposition exists for the development of drug-induced kidney disease (DIKD), using genome-wide association and whole-genome sequencing studies; to describe the frequency, course, risk factors, resolution and outcomes of DIKD cases; to investigate the role of ethnic/racial variability in the genetics of DIKD; and to explore the use of different tools establishing causality of DIKD.MethodsA total of 800 patients will be enrolled worldwide and blood samples for DNA collected. Data on the patient risk factors, vital signs, laboratory parameters, drug exposure, and DIKD course will be recorded. A panel of nephrologists will adjudicate all cases. Genome-wide association studies will be conducted using population controls matched on biogeographic ancestry to determine whether there is a genetic predisposition to DIKD. The primary endpoint is the identification of specific drug-related polymorphisms associated with DIKD. Secondary endpoints include the following: frequency of DIKD by causal drug and drug combinations; DIKD genetic variability; exploration of causality assessment tools; risk factor identification; description of the course of DIKD, including mortality and dialysis dependency at hospital discharge and 28 and 90 days post-event.ResultsData are currently being analyzed. Results are pending.DiscussionThe Genetic Contribution to Drug Induced Renal Injury (DIRECT) study will be the first observational cohort study to investigate the genetic determinants of DIKD. If the trial is positive, its findings will potentially translate into safer patient outcomes, by genotypic individualization of therapy and minimization of harm

Epigenetic meta-analysis across three civilian cohorts identifies NRG1 and HGS as blood-based biomarkers for post-traumatic stress disorder

Aim: Trauma exposure is a necessary, but not deterministic, contributor to post-traumatic stress disorder (PTSD). Epigenetic factors may distinguish between trauma-exposed individuals with versus without PTSD. Materials & methods: We conducted a meta-analysis of PTSD epigenome-wide association studies in trauma-exposed cohorts drawn from civilian contexts. Whole blood-derived DNA methylation levels were analyzed in 545 study participants, drawn from the three civilian cohorts participating in the PTSD working group of the Psychiatric Genomics Consortium. Results: Two CpG sites significantly associated with current PTSD in NRG1 (cg23637605) and in HGS (cg19577098). Conclusion: PTSD is associated with differential methylation, measured in blood, within HGS and NRG1 across three civilian cohorts

High-speed photothermal off-resonance atomic force microscopy reveals assembly routes of centriolar scaffold protein SAS-6

The self-assembly of protein complexes is at the core of many fundamental biological processes1, ranging from the polymerization of cytoskeletal elements, such as microtubules2, to viral capsid formation and organelle assembly3. To reach a comprehensive understanding of the underlying mechanisms of self-assembly, high spatial and temporal resolutions must be attained. This is complicated by the need to not interfere with the reaction during the measurement. As self-assemblies are often governed by weak interactions, they are especially difficult to monitor with high-speed atomic force microscopy (HS-AFM) due to the non-negligible tip–sample interaction forces involved in current methods. We have developed a HS-AFM technique, photothermal off-resonance tapping (PORT), which is gentle enough to monitor self-assembly reactions driven by weak interactions. We apply PORT to dissect the self-assembly reaction of SAS-6 proteins, which form a nine-fold radially symmetric ring-containing structure that seeds the formation of the centriole organelle. Our analysis reveals the kinetics of SAS-6 ring formation and demonstrates that distinct biogenesis routes can be followed to assemble a nine-fold symmetrical structure

A monolithic MEMS position sensor for closed-loop high-speed atomic force microscopy

The accuracy and repeatability of atomic force microscopy (AFM) imaging significantly depend on the accuracy of the piezoactuator. However, nonlinear properties of piezoactuators can distort the image, necessitating sensor-based closed-loop actuators to achieve high accuracy AFM imaging. The advent of high-speed AFM has made the requirements on the position sensors in such a system even more stringent, requiring higher bandwidths and lower sensor mass than traditional sensors can provide. In this paper, we demonstrate a way for high-speed, high-precision closed-loop AFM nanopositioning using a novel, miniaturized micro-electro-mechanical system position sensor in conjunction with a simple PID controller. The sensor was developed to respond to the need for small, lightweight, high-bandwidth, long-range and sub-nm-resolution position measurements in high-speed AFM applications. We demonstrate the use of this sensor for closed-loop operation of conventional as well as high-speed AFM operation to provide distortion-free images. The presented implementation of this closed-loop approach allows for positioning precision down to 2.1 Å, reduces the integral nonlinearity to below 0.2%, and allows for accurate closed loop imaging at line rates up to 300 Hz