Properties of cage rearrangements observed near the colloidal glass transition

We use confocal microscopy to study the motions of particles in concentrated colloidal systems. Near the glass transition, diffusive motion is inhibited, as particles spend time trapped in transient ``cages'' formed by neighboring particles. We measure the cage sizes and lifetimes, which respectively shrink and grow as the glass transition approaches. Cage rearrangements are more prevalent in regions with lower local concentrations and higher disorder. Neighboring rearranging particles typically move in parallel directions, although a nontrivial fraction move in anti-parallel directions, usually from pairs of particles with initial separations corresponding to the local maxima and minima of the pair correlation function $g(r)$, respectively.Comment: 5 pages, 4 figures; text & figures revised in v

Microbe-seq : high-throughput, single-microbe genomics with strain resolution, applied to a human gut microbiome

We present Microbe-seq , a high-throughput single-microbe method that yields strain-resolved genomes from complex microbial communities. We encapsulate individual microbes into droplets with microfluidics and liberate their DNA, which we amplify, tag with droplet-specific barcodes, and sequence. We use Microbe-seq to explore the human gut microbiome; we collect stool samples from a single individual, sequence over 20,000 microbes, and reconstruct nearly-complete genomes of almost 100 bacterial species, including several with multiple subspecies strains. We use these genomes to probe genomic signatures of microbial interactions: we reconstruct the horizontal gene transfer (HGT) network within the individual and observe far greater exchange within the same bacterial phylum than between different phyla. We probe bacteria-virus interactions; unexpectedly, we identify a significant in vivo association between crAssphage, an abundant bacteriophage, and a single strain of Bacteroides vulgatus. Microbe-seq contributes high-throughput culture-free capabilities to investigate genomic blueprints of complex microbial communities with single-microbe resolution

Aeolian features on Venus: Preliminary Magellan results

Magellan synthetic aperture radar data reveal numerous surface features that are attributed to aeolian, or wind processes. Wind streaks are the most common aeolian feature. They consist of radar backscatter patterns that are high, low, or mixed in relation to the surface on which they occur. A data base of more than 3400 wind streaks shows that low backscatter linear forms (long, narrow streaks) are the most common and that most streaks occur between 17°S to 30°S and 5°N to 53°N on smooth plains. Moreover, most streaks are associated with deposits from certain impact craters and some tectonically deformed terrains. We infer that both of these geological settings provide fine particulate material that can be entrained by the low-velocity winds on Venus. Turbulence and wind patterns generated by the topographic features with which many streaks are associated can account for differences in particle distributions and in the patterns of the wind streaks. Thus, some high backscatter streaks are considered to be zones that are swept free of sedimentary particles to expose rough bedrock; other high backscatter streaks may be lag deposits of dense materials from which low-density grains have been removed (dense materials such as ilmenite or pyrite have dielectric properties that would produce high backscatter patterns). Wind streaks generally occur on slopes < 2° and tend to be oriented toward the equator, consistent with the Hadley model of atmospheric circulation. In addition to wind streaks, other aeolian features on Venus include yardangs(?) and dune fields. The Aglaonice dune field, centered at 25°S, 340°E, covers ∼1290 km^2 and is located in an ejecta flow channel from the Aglaonice impact crater. The Meshkenet dune field, located at 67°N, 90°E, covers ∼17,120 km^2 in a valley between Ishtar Terra and Meshkenet Tessera. Wind streaks associated with both dune fields suggest that the dunes are of transverse forms in which the dune crests are perpendicular to the prevailing winds. Dunes on Venus signal the presence of sand-size (∼60 to 2,000 μm) grains. The possible yardangs are found at 9°N, 60.5°E, about 300 km southeast of the crater Mead. Although most aeolian features are concentrated in smooth plains near the equator, the occurrence of wind streaks is widespread, and some have been found at all latitudes and elevations. They demonstrate that aeolian processes operate widely on Venus. The intensity of wind erosion and deposits, however, varies with locality and is dependent on the wind regime and supply of particles

Non-invasive cardiac assessment in high risk patients (The GROUND study): rationale, objectives and design of a multi-center randomized controlled clinical trial

Background: Peripheral arterial disease (PAD) is a common disease associated with a considerably increased risk of future cardiovascular events and most of these patients will die from coronary artery disease (CAD). Screening for silent CAD has become an option with recent non-invasive developments in CT (computed tomography)-angiography and MR (magnetic resonance) stress testing. Screening in combination with more aggressive treatment may improve prognosis. Therefore we propose to study whether a cardiac imaging algorithm, using non-invasive imaging techniques followed by treatment will reduce the risk of cardiovascular disease in PAD patients free from cardiac symptoms. Design: The GROUND study is designed as a prospective, multi-center, randomized clinical trial. Patients with peripheral arterial disease, but without symptomatic cardiac disease will be asked to participate. All patients receive a proper risk factor management before randomization. Half of the recruited patients will enter the 'control group' and only undergo CT calcium scoring. The other half of the recruited patients (index group) will undergo the non invasive cardiac imaging algorithm followed by evidence-based treatment. First, patients are submitted to CT calcium scoring and CT angiography. Patients with a left main (or equivalent) coronary artery stenosis of > 50% on CT will be referred to a cardiologist without further imaging. All other patients in this group will undergo dobutamine stress magnetic resonance (DSMR) testing. Patients with a DSMR positive for ischemia will also be referred to a cardiologist. These patients are candidates for conventional coronary angiography and cardiac interventions (coronary artery bypass grafting (CABG) or percutaneous cardiac interventions (PCI)), if indicated. All participants of the trial will enter a 5 year follow up period for the occurrence of cardiovascular events. Sequential interim analysis will take place. Based on sample size calculations about 1200 patients are needed to detect a 24% reduction in primary outcome. Implications: The GROUND study will provide insight into the question whether non-invasive cardiac imaging reduces the risk of cardiovascular events in patients with peripheral arterial disease, but without symptoms of coronary artery disease. Trial registration: Clinicaltrials.gov NCT0018911

Specific genomic aberrations in primary colorectal cancer are associated with liver metastases

Background: Accurate staging of colorectal cancer (CRC) with clinicopathological parameters is important for predicting prognosis and guiding treatment but provides no information about organ site of metastases. Patterns of genomic aberrations in primary colorectal tumors may reveal a chromosomal signature for organ specific metastases. Methods: Array Comparative Genomic Hybridization (aCGH) was employed to asses DNA copy number changes in primary colorectal tumors of three distinctive patient groups. This included formalin-fixed, paraffin-embedded tissue of patients who developed liver metastases (LM; n = 36), metastases (PM; n = 37) and a group that remained metastases-free (M0; n = 25). A novel statistical method for identifying recurrent copy number changes, KC-SMART, was used to find specific locations of genomic aberrations specific for various groups. We created a classifier for organ specific metastases based on the aCGH data using Prediction Analysis for Microarrays (PAM). Results: Specifically in the tumors of primary CRC patients who subsequently developed liver metastasis, KC-SMART analysis identified genomic aberrations on chromosome 20q. LM-PAM, a shrunken centroids classifier for liver metastases occurrence, was able to distinguish the LM group from the other groups (M0&PM) with 80% accuracy (78% sensitivity and 86% specificity). The classification is predominantly based on chromosome 20q aberrations. Conclusion: Liver specific CRC metastases may be predicted with a high accuracy based on specific genomic aberrations in the primary CRC tumor. The ability to predict the site of metastases is important for improvement of personalized patient management.MediamaticsElectrical Engineering, Mathematics and Computer Scienc

Guidelines for Genome-Scale Analysis of Biological Rhythms

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding “big data” that are conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome-scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them

Guidelines for Genome-Scale Analysis of Biological Rhythms

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding ‘big data’ that is conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them