The combined effects of sidestream smoke extracts and glycated serum albumin on endothelial cells and platelets

Background: The purpose of this study was to test the hypothesis that sidestream tobacco smoke extracts would inhibit the culture of endothelial cells and enhance platelet aggregation under diabetic vascular conditions. Sidestream tobacco smoke and advanced glycation end products are known cardiovascular risk factors and we aimed to determine the combined interaction between these two risk factors to promote cardiovascular diseases associated with diabetes.Methods: Human umbilical vein endothelial cells were cultured in the presence of sidestream tobacco smoke extracts (SHS) or nicotine and glycated albumin (AGE) or non-glycated albumin. After 3 days, endothelial cell viability and density were investigated. Platelets were also incubated with these compounds for up to 6 hours. Platelet aggregation and the surface expression of CD41 and CD62P were examined. In some experiments, platelets were added to the endothelial cell culture to determine if an interaction between platelets and endothelial cells occurs that can alter the responses to SHS or AGE.Results: In general, the endothelial cell culture conditions were reduced in the presence of AGE and SHS. Nicotine, did not play a role in this reduction. Platelet aggregation proceeded faster in the presence of AGE and SHS. Interestingly, with the combined culture of endothelial cells and platelets, the endothelial cell culture conditions were improved and the platelet functional changes were diminished in the presence of SHS and AGE, as compared with the individual incubations.Conclusions: Our data suggests that diabetics that are exposed to SHS may have a higher likelihood for cardiovascular disease development through a diminished endothelial cell viability and an increased platelet activity, which are partially mediated by CD41 and not CD62P. This study provides support for an increased cardiovascular risk for diabetic patients that are exposed to SHS. This study also provides a new experimental technique to monitor platelet-endothelial cell interactions.Peer reviewedMechanical and Aerospace Engineerin

Unfolding cross-linkers as rheology regulators in F-actin networks

We report on the nonlinear mechanical properties of a statistically homogeneous, isotropic semiflexible network cross-linked by polymers containing numerous small unfolding domains, such as the ubiquitous F-actin cross-linker Filamin. We show that the inclusion of such proteins has a dramatic effect on the large strain behavior of the network. Beyond a strain threshold, which depends on network density, the unfolding of protein domains leads to bulk shear softening. Past this critical strain, the network spontaneously organizes itself so that an appreciable fraction of the Filamin cross-linkers are at the threshold of domain unfolding. We discuss via a simple mean-field model the cause of this network organization and suggest that it may be the source of power-law relaxation observed in in vitro and in intracellular microrheology experiments. We present data which fully justifies our model for a simplified network architecture.Comment: 11 pages, 4 figures. to appear in Physical Review

Research Investments and Market Structure in the Food Processing, Agricultural Input, and Biofuel Industries Worldwide

Meeting growing global demand for food, fiber, and biofuel requires robust investment in agricultural research and development (R&D) from both public and private sectors. This study examines global R&D spending by private industry in seven agricultural input sectors, food manufacturing, and biofuel and describes the changing structure of these industries. In 2007 (the latest year for which comprehensive estimates are available), the private sector spent 19.7 billion on food and agricultural research (56 percent in food manufacturing and 44 percent in agricultural input sectors) and accounted for about half of total public and private spending on food and agricultural R&D in high-income countries. In R&D related to biofuel, annual private-sector investments are estimated to have reached 1.47 billion worldwide by 2009. Incentives to invest in R&D are influenced by market structure and other factors. Agricultural input industries have undergone significant structural change over the past two decades, with industry concentration on the rise. A relatively small number of large, multinational firms with global R&D and marketing networks account for most R&D in each input industry. Rising market concentration has not generally been associated with increased R&D investment as a percentage of industry sales.agricultural biotechnology, agricultural chemicals, agricultural inputs, animal breeding, animal health, animal nutrition, aquaculture, biofuel, concentration ratio, crop breeding, crop protection, farm machinery, fertilizers, Herfindahl index, globalization, market share, market structure, research intensity, seed improvement, Productivity Analysis,

Soluble Guanylate Cyclase Generation of cGMP Regulates Migration of MGE Neurons

Here we have provided evidence that nitric oxide-cyclic GMP (NO-cGMP) signaling regulates neurite length and migration of immature neurons derived from the medial ganglionic eminence (MGE). Dlx1/2(-/-) and Lhx6(-/-) mouse mutants, which exhibit MGE interneuron migration defects, have reduced expression of the gene encoding the alpha subunit of a soluble guanylate cyclase (Gucy1A3). Furthermore, Dlx1/2(-/-) mouse mutants have reduced expression of NO synthase 1 (NOS1). Gucy1A3(-/-) mice have a transient reduction in cortical interneuron number. Pharmacological inhibition of soluble guanylate cyclase and NOS activity rapidly induces neurite retraction of MGE cells in vitro and in slice culture and robustly inhibits cell migration from the MGE and caudal ganglionic eminence. We provide evidence that these cellular phenotypes are mediated by activation of the Rho signaling pathway and inhibition of myosin light chain phosphatase activity

Word Embeddings for Entity-annotated Texts

Learned vector representations of words are useful tools for many information retrieval and natural language processing tasks due to their ability to capture lexical semantics. However, while many such tasks involve or even rely on named entities as central components, popular word embedding models have so far failed to include entities as first-class citizens. While it seems intuitive that annotating named entities in the training corpus should result in more intelligent word features for downstream tasks, performance issues arise when popular embedding approaches are naively applied to entity annotated corpora. Not only are the resulting entity embeddings less useful than expected, but one also finds that the performance of the non-entity word embeddings degrades in comparison to those trained on the raw, unannotated corpus. In this paper, we investigate approaches to jointly train word and entity embeddings on a large corpus with automatically annotated and linked entities. We discuss two distinct approaches to the generation of such embeddings, namely the training of state-of-the-art embeddings on raw-text and annotated versions of the corpus, as well as node embeddings of a co-occurrence graph representation of the annotated corpus. We compare the performance of annotated embeddings and classical word embeddings on a variety of word similarity, analogy, and clustering evaluation tasks, and investigate their performance in entity-specific tasks. Our findings show that it takes more than training popular word embedding models on an annotated corpus to create entity embeddings with acceptable performance on common test cases. Based on these results, we discuss how and when node embeddings of the co-occurrence graph representation of the text can restore the performance.Comment: This paper is accepted in 41st European Conference on Information Retrieva

Are superflares on solar analogues caused by extra-solar planets?

Stellar flares with ${10^2-10^7}$ times more energy than the largest solar flare have been detected from 9 normal F and G main sequence stars (Schaefer, King & Deliyannis 1999). These superflares have durations of hours to days and are visible from at least x-ray to optical frequencies. The absence of world-spanning aurorae in historical records and of anomalous extinctions in the geological record indicate that our Sun likely does not suffer superflares. In seeking to explain this new phenomenon, we are struck by its similarity to large stellar flares on RS Canum Venaticorum binary systems, which are caused by magnetic reconnection events associated with the tangling of magnetic fields between the two stars. The superflare stars are certainly not of this class, although we propose a similar flare mechanism. That is, superflares are caused by magnetic reconnection between fields of the primary star and a close-in Jovian planet. Thus, by only invoking known planetary properties and reconnection scenarios, we can explain the energies, durations, and spectra of superflares, as well as explain why our Sun does not have such events.Comment: 13 pages, Accepted for publication in Ap

Indeterminacy of Spatiotemporal Cardiac Alternans

Cardiac alternans, a beat-to-beat alternation in action potential duration (at the cellular level) or in ECG morphology (at the whole heart level), is a marker of ventricular fibrillation, a fatal heart rhythm that kills hundreds of thousands of people in the US each year. Investigating cardiac alternans may lead to a better understanding of the mechanisms of cardiac arrhythmias and eventually better algorithms for the prediction and prevention of such dreadful diseases. In paced cardiac tissue, alternans develops under increasingly shorter pacing period. Existing experimental and theoretical studies adopt the assumption that alternans in homogeneous cardiac tissue is exclusively determined by the pacing period. In contrast, we find that, when calcium-driven alternans develops in cardiac fibers, it may take different spatiotemporal patterns depending on the pacing history. Because there coexist multiple alternans solutions for a given pacing period, the alternans pattern on a fiber becomes unpredictable. Using numerical simulation and theoretical analysis, we show that the coexistence of multiple alternans patterns is induced by the interaction between electrotonic coupling and an instability in calcium cycling.Comment: 20 pages, 10 figures, to be published in Phys. Rev.

Assessing Organizational Readiness for Depression Care Quality Improvement: Relative Commitment and Implementation Capability

Background: Depression is a major cause of morbidity and cost in primary care patient populations. Successful depression improvement models, however, are complex. Based on organizational readiness theory, a practice’s commitment to change and its capability to carry out the change are both important predictors of initiating improvement. We empirically explored the links between relative commitment (i.e., the intention to move forward within the following year) and implementation capability. Methods: The DIAMOND initiative administered organizational surveys to medical and quality improvement leaders from each of 83 primary care practices in Minnesota. Surveys preceded initiation of activities directed at implementation of a collaborative care model for improving depression care. To assess implementation capability, we developed composites of survey items for five types of organizational factors postulated to be collaborative care barriers and facilitators. To assess relative commitment for each practice, we averaged leader ratings on an identical survey question assessing practice priorities. We used multivariable regression analyses to assess the extent to which implementation capability predicted relative commitment. We explored whether relative commitment or implementation capability measures were associated with earlier initiation of DIAMOND improvements. Results: All five implementation capability measures independently predicted practice leaders’ relative commitment to improving depression care in the following year. These included the following: quality improvement culture and attitudes (p = 0.003), depression culture and attitudes (p \u3c0.001), prior depression quality improvement activities (p \u3c0.001), advanced access and tracking capabilities (p = 0.03), and depression collaborative care features in place (p = 0.03). Higher relative commitment (p = 0.002) and prior depression quality improvement activities appeared to be associated with earlier participation in the DIAMOND initiative. Conclusions: The study supports the concept of organizational readiness to improve quality of care and the use of practice leader surveys to assess it. Practice leaders’ relative commitment to depression care improvement may be a useful measure of the likelihood that a practice is ready to initiate evidence-based depression care changes. A comprehensive organizational assessment of implementation capability for depression care improvement may identify specific barriers or facilitators to readiness that require targeted attention from implementers