Flight of the dragonflies and damselflies

This work is a synthesis of our current understanding of the mechanics, aerodynamics and visually mediated control of dragonfly and damselfly flight, with the addition of new experimental and computational data in several key areas. These are: the diversity of dragonfly wing morphologies, the aerodynamics of gliding flight, force generation in flapping flight, aerodynamic efficiency, comparative flight performance and pursuit strategies during predatory and territorial flights. New data are set in context by brief reviews covering anatomy at several scales, insect aerodynamics, neuromechanics and behaviour. We achieve a new perspective by means of a diverse range of techniques, including laser-line mapping of wing topographies, computational fluid dynamics simulations of finely detailed wing geometries, quantitative imaging using particle image velocimetry of on-wing and wake flow patterns, classical aerodynamic theory, photography in the field, infrared motion capture and multi-camera optical tracking of free flight trajectories in laboratory environments. Our comprehensive approach enables a novel synthesis of datasets and subfields that integrates many aspects of flight from the neurobiology of the compound eye, through the aeromechanical interface with the surrounding fluid, to flight performance under cruising and higher-energy behavioural modes

Quantized Nambu-Poisson Manifolds in a 3-Lie Algebra Reduced Model

We consider dimensional reduction of the Bagger-Lambert-Gustavsson theory to a zero-dimensional 3-Lie algebra model and construct various stable solutions corresponding to quantized Nambu-Poisson manifolds. A recently proposed Higgs mechanism reduces this model to the IKKT matrix model. We find that in the strong coupling limit, our solutions correspond to ordinary noncommutative spaces arising as stable solutions in the IKKT model with D-brane backgrounds. In particular, this happens for S^3, R^3 and five-dimensional Neveu-Schwarz Hpp-waves. We expand our model around these backgrounds and find effective noncommutative field theories with complicated interactions involving higher-derivative terms. We also describe the relation of our reduced model to a cubic supermatrix model based on an osp(1|32) supersymmetry algebra.Comment: 22 page

Pirfenidone in idiopathic pulmonary fibrosis:expert panel discussion on the management of drug-related adverse events

Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.Correction in: Advances in Therapy, Volume 31, Issue 5, pp 575-576 , doi: 10.1007/s12325-014-0118-8</p

Mixed reality simulation of rasping procedure in artificial cervical disc replacement (ACDR) surgery

<p>Abstract</p> <p>Background</p> <p>Until quite recently spinal disorder problems in the U.S. have been operated by fusing cervical vertebrae instead of replacement of the cervical disc with an artificial disc. Cervical disc replacement is a recently approved procedure in the U.S. It is one of the most challenging surgical procedures in the medical field due to the deficiencies in available diagnostic tools and insufficient number of surgical practices For physicians and surgical instrument developers, it is critical to understand how to successfully deploy the new artificial disc replacement systems. Without proper understanding and practice of the deployment procedure, it is possible to injure the vertebral body. Mixed reality (MR) and virtual reality (VR) surgical simulators are becoming an indispensable part of physicians’ training, since they offer a risk free training environment. In this study, MR simulation framework and intricacies involved in the development of a MR simulator for the rasping procedure in artificial cervical disc replacement (ACDR) surgery are investigated. The major components that make up the MR surgical simulator with motion tracking system are addressed. </p> <p>Findings</p> <p>A mixed reality surgical simulator that targets rasping procedure in the artificial cervical disc replacement surgery with a VICON motion tracking system was developed. There were several challenges in the development of MR surgical simulator. First, the assembly of different hardware components for surgical simulation development that involves knowledge and application of interdisciplinary fields such as signal processing, computer vision and graphics, along with the design and placements of sensors etc . Second challenge was the creation of a physically correct model of the rasping procedure in order to attain critical forces. This challenge was handled with finite element modeling. The third challenge was minimization of error in mapping movements of an actor in real model to a virtual model in a process called registration. This issue was overcome by a two-way (virtual object to real domain and real domain to virtual object) semi-automatic registration method.</p> <p>Conclusions</p> <p>The applicability of the VICON MR setting for the ACDR surgical simulator is demonstrated. The main stream problems encountered in MR surgical simulator development are addressed. First, an effective environment for MR surgical development is constructed. Second, the strain and the stress intensities and critical forces are simulated under the various rasp instrument loadings with impacts that are applied on intervertebral surfaces of the anterior vertebrae throughout the rasping procedure. Third, two approaches are introduced to solve the registration problem in MR setting. Results show that our system creates an effective environment for surgical simulation development and solves tedious and time-consuming registration problems caused by misalignments. Further, the MR ACDR surgery simulator was tested by 5 different physicians who found that the MR simulator is effective enough to teach the anatomical details of cervical discs and to grasp the basics of the ACDR surgery and rasping procedure</p

Excision Repair Cross-Complementation Group 1 (ERCC1) Status and Lung Cancer Outcomes: A Meta-Analysis of Published Studies and Recommendations

Despite discrepant results on clinical utility, several trials are already prospectively randomizing non-small cell lung cancer (NSCLC) patients by ERCC1 status. We aimed to characterize the prognostic and predictive effect of ERCC1 by systematic review and meta-analysis.Eligible studies assessed survival and/or chemotherapy response in NSCLC or SCLC by ERCC1 status. Effect measures of interest were hazard ratio (HR) for survival or relative risk (RR) for chemotherapy response. Random-effects meta-analyses were used to account for between-study heterogeneity, with unadjusted/adjusted effect estimates considered separately.23 eligible studies provided survival results in 2,726 patients. Substantial heterogeneity was observed in all meta-analyses (I(2) always >30%), partly due to variability in thresholds defining 'low' and 'high' ERCC1. Meta-analysis of unadjusted estimates showed high ERCC1 was associated with significantly worse overall survival in platinum-treated NSCLC (average unadjusted HR = 1.61, 95%CI:1.23-2.1, p = 0.014), but not in NSCLC untreated with chemotherapy (average unadjusted HR = 0.82, 95%CI:0.51-1.31). Meta-analysis of adjusted estimates was limited by variable choice of adjustment factors and potential publication bias (Egger's p<0.0001). There was evidence that high ERCC1 was associated with reduced response to platinum (average RR = 0.80; 95%CI:0.64-0.99). SCLC data were inadequate to draw firm conclusions.Current evidence suggests high ERCC1 may adversely influence survival and response in platinum-treated NSCLC patients, but not in non-platinum treated, although definitive evidence of a predictive influence is lacking. International consensus is urgently required to provide consistent, validated ERCC1 assessment methodology. ERCC1 assessment for treatment selection should currently be restricted to, and evaluated within, clinical trials

Socio-economic status, racial composition and the affordability of fresh fruits and vegetables in neighborhoods of a large rural region in Texas

<p>Abstract</p> <p>Background</p> <p>Little is known about how affordability of healthy food varies with community characteristics in rural settings. We examined how the cost of fresh fruit and vegetables varies with the economic and demographic characteristics in six rural counties of Texas.</p> <p>Methods</p> <p>Ground-truthed data from the Brazos Valley Food Environment Project were used to identify all food stores in the rural region and the availability and lowest price of fresh whole fruit and vegetables in the food stores. Socioeconomic characteristics were extracted from the 2000 U.S. Census Summary Files 3 at the level of the census block group. We used an imputation strategy to calculate two types of price indices for both fresh fruit and fresh vegetables: a <it>high variety </it>and a <it>basic </it>index; and evaluated the relationship between neighborhood economic and demographic characteristics and affordability of fresh produce, using linear regression models.</p> <p>Results</p> <p>The mean cost of meeting the USDA recommendation of fruit consumption from a high variety basket of fruit types in our sample of stores was just over $27.50 per week. Relying on the three most common fruits lowered the weekly expense to under$17.25 per week, a reduction of 37.6%. The effect of moving from a high variety to a low variety basket was much less when considering vegetable consumption: a 4.3% decline from $29.23 to$27.97 per week. Univariate regression analysis revealed that the cost of fresh produce is not associated with the racial/ethnic composition of the local community. However, multivariate regression showed that holding median income constant, stores in neighborhoods with higher percentages of Black residents paid more for fresh fruits and vegetables. The proportion of Hispanic residents was not associated with cost in either the univariate or multivariate analysis.</p> <p>Conclusion</p> <p>This study extends prior work by examining the affordability of fresh fruit and vegetables from food stores in a large rural area; and how access to an affordable supply of fresh fruit and vegetables differs by neighborhood inequalities. The approach and findings of this study are relevant and have important research and policy implications for understanding access and availability of affordable, healthy foods.</p

The EYA Tyrosine Phosphatase Activity Is Pro-Angiogenic and Is Inhibited by Benzbromarone

Eyes Absents (EYA) are multifunctional proteins best known for their role in organogenesis. There is accumulating evidence that overexpression of EYAs in breast and ovarian cancers, and in malignant peripheral nerve sheath tumors, correlates with tumor growth and increased metastasis. The EYA protein is both a transcriptional activator and a tyrosine phosphatase, and the tyrosine phosphatase activity promotes single cell motility of mammary epithelial cells. Since EYAs are expressed in vascular endothelial cells and cell motility is a critical feature of angiogenesis we investigated the role of EYAs in this process. Using RNA interference techniques we show that EYA3 depletion in human umbilical vein endothelial cells inhibits transwell migration as well as Matrigel-induced tube formation. To specifically query the role of the EYA tyrosine phosphatase activity we employed a chemical biology approach. Through an experimental screen the uricosuric agents Benzbromarone and Benzarone were found to be potent EYA inhibitors, and Benzarone in particular exhibited selectivity towards EYA versus a representative classical protein tyrosine phosphatase, PTP1B. These compounds inhibit the motility of mammary epithelial cells over-expressing EYA2 as well as the motility of endothelial cells. Furthermore, they attenuate tubulogenesis in matrigel and sprouting angiogenesis in the ex vivo aortic ring assay in a dose-dependent fashion. The anti-angiogenic effect of the inhibitors was also demonstrated in vivo, as treatment of zebrafish embryos led to significant and dose-dependent defects in the developing vasculature. Taken together our results demonstrate that the EYA tyrosine phosphatase activity is pro-angiogenic and that Benzbromarone and Benzarone are attractive candidates for repurposing as drugs for the treatment of cancer metastasis, tumor angiogenesis, and vasculopathies

Regulation of type 1 diabetes development and B-cell activation in nonobese diabetic mice by early life exposure to a diabetogenic environment

Microbes, including viruses, influence type 1 diabetes (T1D) development, but many such influences remain undefined. Previous work on underlying immune mechanisms has focussed on cytokines and T cells. Here, we compared two nonobese diabetic (NOD) mouse colonies, NODlow and NODhigh, differing markedly in their cumulative T1D incidence (22% vs. 90% by 30 weeks in females). NODhigh mice harbored more complex intestinal microbiota, including several pathobionts; both colonies harbored segmented filamentous bacteria (SFB), thought to suppress T1D. Young NODhigh females had increased B-cell activation in their mesenteric lymph nodes. These phenotypes were transmissible. Co-housing of NODlow with NODhigh mice after weaning did not change T1D development, but T1D incidence was increased in female offspring of co-housed NODlow mice, which were exposed to the NODhigh environment both before and after weaning. These offspring also acquired microbiota and B-cell activation approaching those of NODhigh mice. In NODlow females, the low rate of T1D was unaffected by cyclophosphamide but increased by PD-L1 blockade. Thus, environmental exposures that are innocuous later in life may promote T1D progression if acquired early during immune development, possibly by altering B-cell activation and/or PD-L1 function. Moreover, T1D suppression in NOD mice by SFB may depend on the presence of other microbial influences. The complexity of microbial immune regulation revealed in this murine model may also be relevant to the environmental regulation of human T1D

Biomedical Discovery Acceleration, with Applications to Craniofacial Development

The profusion of high-throughput instruments and the explosion of new results in the scientific literature, particularly in molecular biomedicine, is both a blessing and a curse to the bench researcher. Even knowledgeable and experienced scientists can benefit from computational tools that help navigate this vast and rapidly evolving terrain. In this paper, we describe a novel computational approach to this challenge, a knowledge-based system that combines reading, reasoning, and reporting methods to facilitate analysis of experimental data. Reading methods extract information from external resources, either by parsing structured data or using biomedical language processing to extract information from unstructured data, and track knowledge provenance. Reasoning methods enrich the knowledge that results from reading by, for example, noting two genes that are annotated to the same ontology term or database entry. Reasoning is also used to combine all sources into a knowledge network that represents the integration of all sorts of relationships between a pair of genes, and to calculate a combined reliability score. Reporting methods combine the knowledge network with a congruent network constructed from experimental data and visualize the combined network in a tool that facilitates the knowledge-based analysis of that data. An implementation of this approach, called the Hanalyzer, is demonstrated on a large-scale gene expression array dataset relevant to craniofacial development. The use of the tool was critical in the creation of hypotheses regarding the roles of four genes never previously characterized as involved in craniofacial development; each of these hypotheses was validated by further experimental work

Occupational exposure to formaldehyde, hematotoxicity and leukemia-specific chromosome changes in cultured myeloid progenitor cells - Response

There are concerns about the health effects of formaldehyde exposure, including carcinogenicity, in light of elevated indoor air levels in new homes and occupational exposures experienced by workers in health care, embalming, manufacturing and other industries. Epidemiological studies suggest that formaldehyde exposure is associated with an increased risk of leukemia. However, the biological plausibility of these findings has been questioned because limited information is available on formaldehyde’s ability to disrupt hematopoietic function. Our objective was to determine if formaldehyde exposure disrupts hematopoietic function and produces leukemia-related chromosome changes in exposed humans. We examined the ability of formaldehyde to disrupt hematopoiesis in a study of 94 workers in China (43 exposed to formaldehyde and 51 frequency-matched controls) by measuring complete blood counts and peripheral stem/progenitor cell colony formation. Further, myeloid progenitor cells, the target for leukemogenesis, were cultured from the workers to quantify the level of leukemia-specific chromosome changes, including monosomy 7 and trisomy 8, in metaphase spreads of these cells. Among exposed workers, peripheral blood cell counts were significantly lowered in a manner consistent with toxic effects on the bone marrow and leukemia-specific chromosome changes were significantly elevated in myeloid blood progenitor cells. These findings suggest that formaldehyde exposure can have an adverse impact on the hematopoietic system and that leukemia induction by formaldehyde is biologically plausible, which heightens concerns about its leukemogenic potential from occupational and environmental exposures