Quantifying Reproducibility in Computational Biology: The Case of the Tuberculosis Drugome

How easy is it to reproduce the results found in a typical computational biology paper? Either through experience or intuition the reader will already know that the answer is with difficulty or not at all. In this paper we attempt to quantify this difficulty by reproducing a previously published paper for different classes of users (ranging from users with little expertise to domain experts) and suggest ways in which the situation might be improved. Quantification is achieved by estimating the time required to reproduce each of the steps in the method described in the original paper and make them part of an explicit workflow that reproduces the original results. Reproducing the method took several months of effort, and required using new versions and new software that posed challenges to reconstructing and validating the results. The quantification leads to “reproducibility maps” that reveal that novice researchers would only be able to reproduce a few of the steps in the method, and that only expert researchers with advance knowledge of the domain would be able to reproduce the method in its entirety. The workflow itself is published as an online resource together with supporting software and data. The paper concludes with a brief discussion of the complexities of requiring reproducibility in terms of cost versus benefit, and a desiderata with our observations and guidelines for improving reproducibility. This has implications not only in reproducing the work of others from published papers, but reproducing work from one’s own laboratory

A distance estimate based on angular expansion for the planetary nebula NGC 6881

In this paper, we report on high angular resolution radio observations of the planetary nebula NGC 6881 obtained with the Very Large Array at a wavelength of 6 cm. The emission appears to be the superposition of a roundish core and a point-symmetric bipolar structure elongated along a position angle of about 145$^\circ$. This is strongly reminiscent of the morphology seen in H$\alpha$ and [NII] images. A comparison between VLA observations obtained in 1984 and 1994 clearly reveals the expansion of the core of the nebula, at a rate of 2.1 $\pm$ 0.7 mas yr$^{-1}$. Assuming that the expansion velocity in the plane of the sky (determined from these measurements) and the expansion velocity along the line of sight (estimated from optical spectroscopy available in the literature) are equal, we find a distance to NGC 6881 of 1.6 $\pm$ 0.5 kpc $\pm$ 0.3 kpc, where the first error reflects the uncertainty on the expansion, and the second error comes from the potential difference between pattern and material speeds. This distance is compatible with (but does not necessarily imply) an association of NGC 6881 with the nearby HII region Sh 2-109 and, more generally, the Cygnus star-forming region.Comment: 5 pages, 3 figure

Analysis of trace metals (Cu, Cd, Pb, and Fe) in seawater using single batch nitrilotriacetate resin extraction and isotope dilution inductively coupled plasma mass spectrometry

A simple and accurate low-blank method has been developed for the analysis of total dissolved copper, cadmium, lead, and iron in a small volume (1.3–1.5 mL per element) of seawater. Pre-concentration and salt-separation of a stable isotope spiked sample are achieved by single batch extraction onto nitrilotriacetate (NTA)-type Superflow® chelating resin beads (100–2400 beads depending on the element). Metals are released into 0.1–0.5 M HNO[subscript 3], and trace metal isotope ratios are determined by ICPMS. The benefit of this method compared to our previous Mg(OH)2 coprecipitation method is that the final matrix is very dilute so cone-clogging and matrix sensitivity suppression are minimal, while still retaining the high accuracy of the isotope dilution technique. Recovery efficiencies are sensitive to sample pH, number of resin beads added, and the length of time allowed for sample–resin binding and elution; these factors are optimized for each element to yield the highest recovery. The method has a low procedural blank and high sensitivity sufficient for the analysis of pM–nM open-ocean trace metal concentrations. Application of this method to samples from the Bermuda Atlantic Time-Series Study station provides oceanographically consistent Cu, Cd, Pb, and Fe profiles that are in good agreement with other reliable data for this site. In addition, the method can potentially be modified for the simultaneous analysis of multiple elements, which will be beneficial for the analysis of large number of samples.National Science Foundation (U.S.) (NSF frant OCE-0751409)Kuwait Foundation for the Advancement of SciencesNational Science Foundation (U.S.) (NSF award OCE-0751409)National Science Foundation (U.S.) (NSF award OCE-0926197

An optimization model for line planning and timetabling in automated urban metro subway networks

In this paper we present a Mixed Integer Nonlinear Programming model that we developed as part of a pilot study requested by the R&D company Metrolab in order to design tools for finding solutions for line planning and timetable situations in automated urban metro subway networks. Our model incorporates important factors in public transportation systems from both, a cost-oriented and a passenger-oriented perspective, as time-dependent demands, interchange stations, short-turns and technical features of the trains in use. The incoming flows of passengers are modeled by means of piecewise linear demand functions which are parameterized in terms of arrival rates and bulk arrivals. Decisions about frequencies, train capacities, short-turning and timetables for a given planning horizon are jointly integrated to be optimized in our model. Finally, a novel Math-Heuristic approach is proposed to solve the problem. The results of extensive computational experiments are reported to show its applicability and effectiveness to handle real-world subway networksComment: 30 pages, 6 figures, 9 table

Distinct sub-second dopamine signaling in dorsolateral striatum measured by a genetically-encoded fluorescent sensor

The development of genetically encoded dopamine sensors such as dLight has provided a new approach to measuring slow and fast dopamine dynamics both in brain slices and in vivo, possibly enabling dopamine measurements in areas like the dorsolateral striatum (DLS) where previously such recordings with fast-scan cyclic voltammetry (FSCV) were difficult. To test this, we first evaluated dLight photometry in mouse brain slices with simultaneous FSCV and found that both techniques yielded comparable results, but notable differences in responses to dopamine transporter inhibitors, including cocaine. We then used in vivo fiber photometry with dLight in mice to examine responses to cocaine in DLS. We also compared dopamine responses during Pavlovian conditioning across the striatum. We show that dopamine increases were readily detectable in DLS and describe transient dopamine kinetics, as well as slowly developing signals during conditioning. Overall, our findings indicate that dLight photometry is well suited to measuring dopamine dynamics in DLS

An Electronic Nose for Reliable Measurement and Correct Classification of Beverages

This paper reports the design of an electronic nose (E-nose) prototype for reliable measurement and correct classification of beverages. The prototype was developed and fabricated in the laboratory using commercially available metal oxide gas sensors and a temperature sensor. The repeatability, reproducibility and discriminative ability of the developed E-nose prototype were tested on odors emanating from different beverages such as blackcurrant juice, mango juice and orange juice, respectively. Repeated measurements of three beverages showed very high correlation (r > 0.97) between the same beverages to verify the repeatability. The prototype also produced highly correlated patterns (r > 0.97) in the measurement of beverages using different sensor batches to verify its reproducibility. The E-nose prototype also possessed good discriminative ability whereby it was able to produce different patterns for different beverages, different milk heat treatments (ultra high temperature, pasteurization) and fresh and spoiled milks. The discriminative ability of the E-nose was evaluated using Principal Component Analysis and a Multi Layer Perception Neural Network, with both methods showing good classification results

Study on the Self-Repairing Effect of Nanoclay in Powder Coatings for Corrosion Protection

Powder coatings are a promising, solvent-free alternative to traditional liquid coatings due to the superior corrosion protection they provide. This study investigates the effects of incorporating montmorillonite-based nanoclay additives with different particle sizes into polyester/triglycidyl isocyanurate (polyester/TGIC) powder coatings. The objective is to enhance the corrosion-protective function of the coatings while addressing the limitations of commonly employed epoxy-based coating systems that exhibit inferior UV resistance. The anti-corrosive and surface qualities of the coatings were evaluated via neutral salt spray tests, electrochemical measurements, and surface analytical techniques. Results show that the nanoclay with a larger particle size of 18.38 µm (D50, V) exhibits a better barrier effect at a lower dosage of 4%, while a high dosage leads to severe defects in the coating film. Interestingly, the coating capacitance is found, via electrochemical impedance spectroscopy, to decrease during the immersion test, indicating a self-repairing capability of the nanoclay, arising from its swelling and expansion. Neutral salt spray tests suggest an optimal nanoclay dosage of 2%, with the smaller particle size (8.64 µm, D50, V) nanoclay providing protection for 1.5 times as many salt spray hours as the nanoclay with a larger particle size. Overall, incorporating montmorillonite-based nanoclay additives is suggested to be a cost-effective approach for significantly enhancing the anti-corrosive function of powder coatings, expanding their application to outdoor environments

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Consensus Statement on Proton Therapy in Mesothelioma

Purpose: Radiation therapy for mesothelioma remains challenging, as normal tissue toxicity limits the amount of radiation that can be safely delivered to the pleural surfaces, especially radiation dose to the contralateral lung. The physical properties of proton therapy result in better sparing of normal tissues when treating the pleura, both in the postpneumonectomy setting and the lung-intact setting. Compared with photon radiation, there are dramatic reductions in dose to the contralateral lung, heart, liver, kidneys, and stomach. However, the tissue heterogeneity in the thorax, organ motion, and potential for changing anatomy during the treatment course all present challenges to optimal irradiation with protons. Methods: The clinical data underlying proton therapy in mesothelioma are reviewed here, including indications, advantages, and limitations. Results: The Particle Therapy Cooperative Group Thoracic Subcommittee task group provides specific guidelines for the use of proton therapy for mesothelioma. Conclusions: This consensus report can be used to guide clinical practice, insurance approval, and future research