Formal Concept Lattice Representations and Algorithms for Hypergraphs

There is increasing focus on analyzing data represented as hypergraphs, which are better able to express complex relationships amongst entities than are graphs. Much of the critical information about hypergraph structure is available only in the intersection relationships of the hyperedges, and so forming the "intersection complex" of a hypergraph is quite valuable. This identifies a valuable isomorphism between the intersection complex and the "concept lattice" formed from taking the hypergraph's incidence matrix as a "formal context": hypergraphs also generalize graphs in that their incidence matrices are arbitrary Boolean matrices. This isomorphism allows connecting discrete algorithms for lattices and hypergraphs, in particular s-walks or s-paths on hypergraphs can be mapped to order theoretical operations on the concept lattice. We give new algorithms for formal concept lattices and hypergraph s-walks on concept lattices. We apply this to a large real-world dataset and find deep lattices implying high interconnectivity and complex geometry of hyperedges

Ratings Changes, Ratings Levels, and the Predictive Value of Analysts’ Recommendations

We show that abnormal returns to analysts’ recommendations stem from both the ratings levels assigned and the changes in those ratings. Conditional on the ratings change, buy and strong buy recommendations have greater returns than do holds, sells, and strong sells. Conditional on the ratings level, upgrades earn the highest returns and downgrades the lowest. We also find that both ratings levels and changes predict future unexpected earnings and the associated market reaction. Our results imply that 1) investment returns may be enhanced by conditioning on both recommendation levels and changes; 2) the predictive power of analysts’ recommendations reflects, at least partially, analysts’ ability to generate valuable private information; and 3) some inconsistency exists between analysts’ ratings and the formal ratings definitions issued by securities firms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79054/1/j.1755-053X.2010.01083.x.pd

Q-Strategy: A Bidding Strategy for Market-Based Allocation of Grid Services

The application of autonomous agents by the provisioning and usage of computational services is an attractive research field. Various methods and technologies in the area of artificial intelligence, statistics and economics are playing together to achieve i) autonomic service provisioning and usage of Grid services, to invent ii) competitive bidding strategies for widely used market mechanisms and to iii) incentivize consumers and providers to use such market-based systems. The contributions of the paper are threefold. First, we present a bidding agent framework for implementing artificial bidding agents, supporting consumers and providers in technical and economic preference elicitation as well as automated bid generation by the requesting and provisioning of Grid services. Secondly, we introduce a novel consumer-side bidding strategy, which enables a goal-oriented and strategic behavior by the generation and submission of consumer service requests and selection of provider offers. Thirdly, we evaluate and compare the Q-strategy, implemented within the presented framework, against the Truth-Telling bidding strategy in three mechanisms – a centralized CDA, a decentralized on-line machine scheduling and a FIFO-scheduling mechanisms

Collagen I Modifies Connexin‐43 Hemichannel Activity via Integrin α2β1 Binding in TGFβ1‐Evoked Renal Tubular Epithelial Cells

Chronic Kidney Disease (CKD) is associated with sustained inflammation and progressive fibrosis, changes that have been linked to altered connexin hemichannel‐mediated release of adenosine triphosphate (ATP). Kidney fibrosis develops in response to increased deposition of extracellular matrix (ECM), and up‐regulation of collagen I is an early marker of renal disease. With ECM remodeling known to promote a loss of epithelial stability, in the current study we used a clonal human kidney (HK2) model of proximal tubular epithelial cells to determine if collagen I modulates changes in cell function, via connexin‐43 (Cx43) hemichannel ATP release. HK2 cells were cultured on collagen I and treated with the beta 1 isoform of the pro‐fibrotic cytokine transforming growth factor (TGFβ1) ± the Cx43 mimetic Peptide 5 and/or an anti‐integrin α2β1 neutralizing antibody. Phase microscopy and immunocytochemistry observed changes in cell morphology and cytoskeletal reorganization, whilst immunoblotting and ELISA identified changes in protein expression and secretion. Carboxyfluorescein dye uptake and biosensing measured hemichannel activity and ATP release. A Cytoselect extracellular matrix adhesion assay assessed changes in cell‐substrate interactions. Collagen I and TGFβ1 synergistically evoked increased hemichannel activity and ATP release. This was paralleled by changes to markers of tubular injury, partly mediated by integrin α2β1/integrin‐like kinase signaling. The co‐incubation of the hemichannel blocker Peptide 5, reduced collagen I/TGFβ1 induced alterations and inhibited a positive feedforward loop between Cx43/ATP release/collagen I. This study highlights a role for collagen I in regulating connexin‐mediated hemichannel activity through integrin α2β1 signaling, ahead of establishing Peptide 5 as a potential intervention

Optimizing sequencing protocols for leaderboard metagenomics by combining long and short reads.

As metagenomic studies move to increasing numbers of samples, communities like the human gut may benefit more from the assembly of abundant microbes in many samples, rather than the exhaustive assembly of fewer samples. We term this approach leaderboard metagenome sequencing. To explore protocol optimization for leaderboard metagenomics in real samples, we introduce a benchmark of library prep and sequencing using internal references generated by synthetic long-read technology, allowing us to evaluate high-throughput library preparation methods against gold-standard reference genomes derived from the samples themselves. We introduce a low-cost protocol for high-throughput library preparation and sequencing

Menthol Suppresses Nicotinic Acetylcholine Receptor Functioning in Sensory Neurons via Allosteric Modulation

In this study, we have investigated how the function of native and recombinant nicotinic acetylcholine receptors (nAChRs) is modulated by the monoterpenoid alcohol from peppermint (−) menthol. In trigeminal neurons (TG), we found that nicotine (75 μM)-activated whole-cell currents through nAChRs were reversibly reduced by menthol in a concentration-dependent manner with an IC50 of 111 μM. To analyze the mechanism underlying menthol's action in more detail, we used single channel and whole-cell recordings from recombinant human α4β2 nAChR expressed in HEK tsA201 cells. Here, we found a shortening of channel open time and a prolongation of channel closed time, and an increase in single channel amplitude leading in summary to a reduction in single channel current. Furthermore, menthol did not affect nicotine's EC50 value for currents through recombinant human α4β2 nAChRs but caused a significant reduction in nicotine's efficacy. Taken together, these findings indicate that menthol is a negative allosteric modulator of nAChRs

Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis

Regulatory T (Treg) cells respond to immune and inflammatory signals to mediate immunosuppression, but how functional integrity of Treg cells is maintained under activating environments remains elusive. Here we found that autophagy was active in Treg cells and supported their lineage stability and survival fitness. Treg cell-specific deletion of the essential autophagy gene Atg7 or Atg5 led to loss of Treg cells, increased tumor resistance, and development of inflammatory disorders. Atg7-deficient Treg cells had increased apoptosis and readily lost Foxp3 expression, especially after activation. Mechanistically, autophagy deficiency upregulated mTORC1 and c-Myc function and glycolytic metabolism that contributed to defective Treg function. Therefore, autophagy couples environmental signals and metabolic homeostasis to protect lineage and survival integrity of Treg cells in activating contexts

Inflation and Dark Energy from spectroscopy at z > 2

The expansion of the Universe is understood to have accelerated during two epochs: in its very first moments during a period of Inflation and much more recently, at z < 1, when Dark Energy is hypothesized to drive cosmic acceleration. The undiscovered mechanisms behind these two epochs represent some of the most important open problems in fundamental physics. The large cosmological volume at 2 < z < 5, together with the ability to efficiently target high-$z$ galaxies with known techniques, enables large gains in the study of Inflation and Dark Energy. A future spectroscopic survey can test the Gaussianity of the initial conditions up to a factor of ~50 better than our current bounds, crossing the crucial theoretical threshold of $\sigma(f_{NL}^{\rm local})$ of order unity that separates single field and multi-field models. Simultaneously, it can measure the fraction of Dark Energy at the percent level up to $z = 5$, thus serving as an unprecedented test of the standard model and opening up a tremendous discovery space

Transmission of Single HIV-1 Genomes and Dynamics of Early Immune Escape Revealed by Ultra-Deep Sequencing

We used ultra-deep sequencing to obtain tens of thousands of HIV-1 sequences from regions targeted by CD8+ T lymphocytes from longitudinal samples from three acutely infected subjects, and modeled viral evolution during the critical first weeks of infection. Previous studies suggested that a single virus established productive infection, but these conclusions were tempered because of limited sampling; now, we have greatly increased our confidence in this observation through modeling the observed earliest sample diversity based on vastly more extensive sampling. Conventional sequencing of HIV-1 from acute/early infection has shown different patterns of escape at different epitopes; we investigated the earliest escapes in exquisite detail. Over 3–6 weeks, ultradeep sequencing revealed that the virus explored an extraordinary array of potential escape routes in the process of evading the earliest CD8 T-lymphocyte responses – using 454 sequencing, we identified over 50 variant forms of each targeted epitope during early immune escape, while only 2–7 variants were detected in the same samples via conventional sequencing. In contrast to the diversity seen within epitopes, non-epitope regions, including the Envelope V3 region, which was sequenced as a control in each subject, displayed very low levels of variation. In early infection, in the regions sequenced, the consensus forms did not have a fitness advantage large enough to trigger reversion to consensus amino acids in the absence of immune pressure. In one subject, a genetic bottleneck was observed, with extensive diversity at the second time point narrowing to two dominant escape forms by the third time point, all within two months of infection. Traces of immune escape were observed in the earliest samples, suggesting that immune pressure is present and effective earlier than previously reported; quantifying the loss rate of the founder virus suggests a direct role for CD8 T-lymphocyte responses in viral containment after peak viremia. Dramatic shifts in the frequencies of epitope variants during the first weeks of infection revealed a complex interplay between viral fitness and immune escape

Thermal Perceptual Thresholds are typical in Autism Spectrum Disorder but Strongly Related to Intra-individual Response Variability

Individuals with autism spectrum disorder (ASD) are often reported to exhibit an apparent indifference to pain or temperature. Leading models suggest that this behavior is the result of elevated perceptual thresholds for thermal stimuli, but data to support these assertions are inconclusive. An alternative proposal suggests that the sensory features of ASD arise from increased intra-individual perceptual variability. In this study, we measured method-of-limits warm and cool detection thresholds in 142 individuals (83 with ASD, 59 with typical development [TD], aged 7–54 years), testing relationships with diagnostic group, demographics, and clinical measures. We also investigated the relationship between detection thresholds and a novel measure of intra-individual (trial-to-trial) threshold variability, a putative index of “perceptual noise.” This investigation found no differences in thermal detection thresholds between individuals with ASD and typical controls, despite large differences between groups in sensory reactivity questionnaires and modest group differences in intra-individual variability. Lower performance IQ, male sex, and higher intra-individual variability in threshold estimates were the most significant predictors of elevated detection thresholds. Although no psychophysical measure was significantly correlated with questionnaire measures of sensory hyporeactivity, large intra-individual variability may partially explain the elevated psychophysical thresholds seen in a subset of the ASD population