Neural differentiation of pluripotent stem cells and applications to micropatterned agarose hydrogel for nerve guidance

Many central nervous system (CNS) disorders are attributable to damaged oligodendrocytes, the cells that form the myelin sheath of axons. An effective source of human oligodendrocytes is crucial, making pluripotent stem cells, such as embryonic stem (ES) cells, an attractive source for nerve tissue repair and regeneration due to their unlimited capacity for self-renewal and their ability to differentiate into all major cell lineages. Bioengineered 3-D hydrogel culture systems have the potential to elucidate mechanisms required for regeneration of CNS cells. The goals of this study are: (1) to investigate the effects of retinoic acid (RA), sonic hedgehog (shh) agonist, and glucose levels on neural differentiation of mouse embryonic stem cells (mESCs), and (2) to employ micropatterned agarose hydrogels for nerve guidance. A protocol utilizing embryoid body (EB) formation, under both high and low glucose conditions, was devised for RA-induced neural lineage differentiation and RA/shh-induced oligodendrocyte differentiation. EBs exposed to lower glucose concentrations with agonists exemplified a more rapid differentiation. After 8 days in culture, there was a higher expression level of oligodendrocyte precursor cell markers in low glucose conditions. These results illustrate that physiologic glucose concentrations are more conducive to the development of EBs and favor the differentiation of mESCs into neural lineages. In order to fabricate 3-D microchannel hydrogel structures for nerve guidance, agarose solution was poured onto the plastic mold master with gridded microchannels and peeled off after hydrogel formation. An extracellular matrix (ECM) coating, such as collagen, was used to promote cell adhesion and neurite outgrowth limited to the channels. Exploitation of various cell types, including fibroblasts and PC12 cells, to optimize the hydrogel conditions, exhibited good cell and ECM patterns on the microchannels. Further studies using dorsal root ganglion (DRG) neurons, Schwann cells, and differentiating ES cells demonstrated good cell growth and nerve guidance through the micropatterned channels. Micropatterned hydrogels can be used as an in vitro model to replicate complex tissue organization, and to investigate nerve signal propagation and myelination

Exact Gap Computation for Code Coverage Metrics in ISO-C

Test generation and test data selection are difficult tasks for model based testing. Tests for a program can be meld to a test suite. A lot of research is done to quantify the quality and improve a test suite. Code coverage metrics estimate the quality of a test suite. This quality is fine, if the code coverage value is high or 100%. Unfortunately it might be impossible to achieve 100% code coverage because of dead code for example. There is a gap between the feasible and theoretical maximal possible code coverage value. Our review of the research indicates, none of current research is concerned with exact gap computation. This paper presents a framework to compute such gaps exactly in an ISO-C compatible semantic and similar languages. We describe an efficient approximation of the gap in all the other cases. Thus, a tester can decide if more tests might be able or necessary to achieve better coverage.Comment: In Proceedings MBT 2012, arXiv:1202.582

BlinkML: Efficient Maximum Likelihood Estimation with Probabilistic Guarantees

The rising volume of datasets has made training machine learning (ML) models a major computational cost in the enterprise. Given the iterative nature of model and parameter tuning, many analysts use a small sample of their entire data during their initial stage of analysis to make quick decisions (e.g., what features or hyperparameters to use) and use the entire dataset only in later stages (i.e., when they have converged to a specific model). This sampling, however, is performed in an ad-hoc fashion. Most practitioners cannot precisely capture the effect of sampling on the quality of their model, and eventually on their decision-making process during the tuning phase. Moreover, without systematic support for sampling operators, many optimizations and reuse opportunities are lost. In this paper, we introduce BlinkML, a system for fast, quality-guaranteed ML training. BlinkML allows users to make error-computation tradeoffs: instead of training a model on their full data (i.e., full model), BlinkML can quickly train an approximate model with quality guarantees using a sample. The quality guarantees ensure that, with high probability, the approximate model makes the same predictions as the full model. BlinkML currently supports any ML model that relies on maximum likelihood estimation (MLE), which includes Generalized Linear Models (e.g., linear regression, logistic regression, max entropy classifier, Poisson regression) as well as PPCA (Probabilistic Principal Component Analysis). Our experiments show that BlinkML can speed up the training of large-scale ML tasks by 6.26x-629x while guaranteeing the same predictions, with 95% probability, as the full model.Comment: 22 pages, SIGMOD 201

Designing informative warning signals: Effects of indicator type, modality, and task demand on recognition speed and accuracy

An experiment investigated the assumption that natural indicators which exploit existing learned associations between a signal and an event make more effective warnings than previously unlearned symbolic indicators. Signal modality (visual, auditory) and task demand (low, high) were also manipulated. Warning effectiveness was indexed by accuracy and reaction time (RT) recorded during training and dual task test phases. Thirty-six participants were trained to recognize 4 natural and 4 symbolic indicators, either visual or auditory, paired with critical incidents from an aviation context. As hypothesized, accuracy was greater and RT was faster in response to natural indicators during the training phase. This pattern of responding was upheld in test phase conditions with respect to accuracy but observed in RT only in test phase conditions involving high demand and the auditory modality. Using the experiment as a specific example, we argue for the importance of considering the cognitive contribution of the user (viz., prior learned associations) in the warning design process. Drawing on semiotics and cognitive psychology, we highlight the indexical nature of so-called auditory icons or natural indicators and argue that the cogniser is an indispensable element in the tripartite nature of signification

Novel Technologies for Assessing Dietary Intake: Evaluating the Usability of a Mobile Telephone Food Record Among Adults and Adolescents

The development of a mobile telephone food record has the potential to ameliorate much of the burden associated with current methods of dietary assessment. When using the mobile telephone food record, respondents capture an image of their foods and beverages before and after eating. Methods of image analysis and volume estimation allow for automatic identification and volume estimation of foods. To obtain a suitable image, all foods and beverages and a fiducial marker must be included in the image

13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis

This work was supported by funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (Grant 677542), a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant 107613/Z/15/Z), and the Barts Charity (Grant MGU0343). This work was also funded, in part, by Medical Research Council Advance Course Masters (Grant MR/J015741/1). The authors declare no conflicts of interest

Fully spray-coated triple-cation perovskite solar cells

We use ultrasonic spray-coating to sequentially deposit thin films of tin oxide, a triple-cation perovskite and spiro-OMeTAD, allowing us fabricate perovskite solar cells (PSCs) with a champion reverse scan power conversion efficiency (PCE) of 19.4% on small-area substrates. We show that the use of spray-deposition permits us to rapidly (>80 mm s−1) coat 25 mm × 75 mm substrates that were divided into a series of devices each with an active area of 15.4 mm2, yielding an average PCE of 10.3% and a peak PCE of 16.3%. By connecting seven 15.4 mm2 devices in parallel on a single substrate, we create a device having an effective active area of 1.08 cm2 and a PCE of 12.7%. This work demonstrates the possibility for spray-coating to fabricate high efficiency and low-cost perovskite solar cells at speed

The effect of linking community health centers to a state-level smoker's quitline on rates of cessation assistance

<p>Abstract</p> <p>Background</p> <p>Smoking cessation quitlines are an effective yet largely untapped resource for clinician referrals. The aim of this study was to assess the effect of a fax referral system that links community health centers (CHCs) with the New York State Quitline on rates of provider cessation assistance.</p> <p>Methods</p> <p>This study was conducted in four CHCs using a quasi experimental study design. Two comparison sites offered usual care (expanded vital sign chart stamp that prompted providers to ask about tobacco use, advice smokers to quit, assess readiness, and offer assistance (4As)) and two intervention sites received the chart stamp plus an office-based fax referral link to the New York State Quitline. The fax referral system links patients to a free proactive telephone counseling service. Provider adherence to the 4 As was assessed with 263 pre and 165 post cross sectional patient exit interviews at all four sites.</p> <p>Results</p> <p>Adherence to the 4As increased significantly over time in the intervention sites with no change from baseline in the comparison sites. Intervention sites were 2.4 (p < .008) times more likely to provide referrals to the state Quitline over time than the comparison sites and 1.8 (p < .001) times more likely to offer medication counseling and/or a prescription.</p> <p>Conclusions</p> <p>Referral links between CHCs and state level telephone quitlines may facilitate the provision of cessation assistance by offering clinicians a practical method for referring smokers to this effective service. Further studies are needed to confirm the efficacy of fax referral systems and to identify implementation strategies that work to facilitate the utilization of these systems across a wide range of clinical settings.</p