bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological degradation of aflatoxin M1 by Bacillus pumilus E‐1‐1‐1
Authors: Gu Xinxi , Sun Jilu , Cui Yuqi , Wang Xianghong , Sang Yaxin
Published: September 2018

Aflatoxin M1 (AFM1) is a potent mycotoxin which causes serious health concerns in developing countries, where it is mainly found in milk, meat, and other foods. Biological detoxification is a promising method for eliminating AFM1. The aim of this work was to search for AFM1‐degrading bacterial strains from animal waste, soil, and activated sludge. High‐performance liquid chromatography and Fourier‐transform infrared spectroscopy were used to analyze the AFM1 degradation products. A strain designated E‐1‐1‐1 was obtained from African elephants feces, with the degradation ratio of AFM1 reaching 89.55% in 12 hr. Based on morphology, physiological and biochemical tests, and 16S rRNA gene sequence analysis, strain E‐1‐1‐1 was identified as Bacillus pumilus. The culture supernatant of B. pumilus E‐1‐1‐1 degraded AFM1 effectively, whereas the cells and cell extracts of B. pumilus E‐1‐1‐1 were far less effective. Carbon and nitrogen sources had highly significant effects on the degradation of AFM1 by B. pumilus E‐1‐1‐1. The AFM1‐degrading strain, B. pumilus E1‐1‐1, could have great potential in industrial applications.
The unfolding spectrum of inherited distal myopathies
Authors: Milone Margherita , Liewluck Teerin
Published: September 2018

Distal myopathies are a group of rare muscle diseases characterized by distal weakness at onset. Although acquired myopathies can occasionally present with distal weakness, the majority of distal myopathies have a genetic etiology. Their age of onset varies from early‐childhood to late‐adulthood while the predominant muscle weakness can affect calf, ankle dorsiflexor, or distal upper limb muscles. A spectrum of muscle pathological changes, varying from nonspecific myopathic changes to rimmed vacuoles to myofibrillar pathology to nuclei centralization, have been noted. Likewise, the underlying molecular defect is heterogeneous. In addition, there is emerging evidence that distal myopathies can result from defective proteins encoded by genes causative of neurogenic disorders, be manifestation of multisystem proteinopathies or the result of the altered interplay between different genes. In this review, we provide an overview on the clinical, electrophysiological, pathological, and molecular aspects of distal myopathies, focusing on the most recent developments in the field. Muscle Nerve 59:283–294, 2019
Alternaria‐Toxine treten in Erscheinung
Authors: Rychlik Michael , Gotthardt Marina , Kietz Roland , Maurer Andrea , Gunkel Klara , Asam Stefan , Mönch Sabine
Published: September 2018

Schimmelpilze der Gattung Alternaria sind weit verbreitet, wachsen auf Nutzpflanzen und hinterlassen giftige Stoffwechselprodukte. Aber anders als Aspergillus‐, Penicillium‐ und Fusarium‐Arten sind sie nur wenig untersucht, und für die Toxine existieren keine Höchstgehalte in Lebens‐ und Futtermitteln. Mit neuen Analysenmethoden könnte sich das ändern.
Risikowahrnehmung: Chemiekenntnisse sind gut, reichen aber nicht
Authors: Hartmann Sabrina , Klaschka Ursula
Published: September 2018

Sind Personen mit sehr guten Chemiekenntnissen Experten für die Risikobewertung von gesundheits‐ und umweltgefährdenden Stoffen in Alltagsprodukten?
Vorbilder sichtbar machen
Authors: Nimmesgern Hilde
Published: September 2018

Chancengleichheit ist im Paragraf 2 der GDCh‐Satzung verankert. Was trägt die GDCh dazu bei, Chancengleichheit in der Chemie zu verbessern?
Gehälter in der Industrie
Authors: Zbikowski Frauke
Published: September 2018

Führungskräfte mit wirtschaftswissenschaftlichem Abschluss verdienen mehr als Chemiker.
An efficient difference scheme for the coupled nonlinear fractional Ginzburg–Landau equations with the fractional Laplacian
Authors: Li Meng , Huang Chengming
Published: September 2018

In this article, an efficient difference scheme for the coupled fractional Ginzburg–Landau equations with the fractional Laplacian is studied. We construct the discrete scheme based on the implicit midpoint method in time and a weighted and shifted Grünwald difference method in space. Then, we prove that the scheme is uniquely solvable, and the numerical solutions are bounded and unconditionally convergent in the norm. Finally, numerical tests are given to confirm the theoretical results and show the effectiveness of the scheme.
Assessment of distress and quality of life in rare cancers
Authors: Bergerot Cristiane Decat , Bergerot Paulo Gustavo , Philip Errol J. , De Domenico Edvane Birelo Lopes , Manhaes Maria Fernanda Marcusso , Pedras Renata Nunes , Salgia Meghan M. , Dizman Nazli , Ashing Kimlin Tam , Li Min , Dale William , Pal Sumanta K.
Published: September 2018

Objective

Rare cancers are a heterogeneous group of conditions that can be associated with emotional and physical impairments. In view of the dearth of research in this area, we investigated the quality of life and prevalence of distress in a cohort of patients diagnosed with a rare cancer, classified by the RARECARE definition.

Methods

A cohort of rare cancer patients, treated in a Brazilian public cancer center, was assessed for distress (Distress Thermometer), anxiety/depression (Hospital Anxiety and Depression Scale), and quality of life (Functional Assessment of Cancer Therapy‐General Version). Descriptive statistics were generated, and multivariate analyses were used to identify factors associated with distress, anxiety/depression, and quality of life.

Results

A total of 137 patients (52.6% male, mean age of 50 years; range 18‐90) were identified. Nearly half (49.6%) of patients reported high levels of distress, with 19.7% endorsing anxiety and 15.3% depression. In multivariate analysis, demographic and clinical variables associated with worse psychosocial outcomes included younger age (P < 0.05), female gender (P < 0.01), advanced disease stage (P < 0.01), and engagement in active therapy (P < 0.05).

Conclusions

Patients diagnosed with rare cancer reported poorer psychosocial outcomes and impaired quality of life when compared to the general population of cancer patients. Certain demographic groups (eg, women and younger patients) may benefit from targeted psychosocial interventions.
Structures of the ligand‐binding domain of Helicobacter pylori chemoreceptor TlpA
Authors: Sweeney Emily G. , Perkins Arden , Kallio Karen , James Remington Stephen , Guillemin Karen
Published: September 2018

Bacteria use chemoreceptor proteins to sense and navigate their chemical environments. The most common class of chemoreceptors are transmembrane proteins that sense chemical cues through binding of a small‐molecule ligand to a periplasmic domain, which modulates the receptor's ability to stimulate reversal of the cell's flagella motors. The prevalent gastric pathogen Helicobacter pylori uses such membrane‐bound chemoreceptors, called transducer‐like proteins (Tlp), to colonize and persist within the stomach. TlpA has been implicated in sensing arginine, bicarbonate, and acid, but no experimentally determined protein structures of TlpA were available to better understand ligand binding and signal transduction. Here, we report three crystal structures of the periplasmic portion of TlpA, which contains tandem PAS/Cache domains, similar to a recently published structure of the lactate‐sensing chemoreceptor TlpC from H. pylori. These structures are the first to show a tandem PAS/Cache‐form chemoreceptor in its native homo dimer oligomer, and we identify residues that are key contributers to the dimer interface. We performed sequence analyses to identify TlpA and TlpC homologs and used residue conservation among these homologs to implicate regions important for the general tandem PAS/Cache fold, and residues specific to TlpA function. Comparisons with TlpC show that despite high similarity across the general structure, TlpA lacks the residues required to bind lactate, and instead contains a pocket almost entirely hydrophobic in nature.
Prevalence of Refractive Errors in Iranian University Students in Kazerun
Authors: Hashemi Hassan , Pakzad Reza , Ali Babak , Yekta Abbasali , Ostadimoghaddam Hadi , Heravian Javad , Yekta Reyhaneh , Khabazkhoob Mehdi
Published: September 2018

Purpose:

To determine the prevalence of refractive errors and visual impairment and the correlation between personal characteristics, including age, sex, weight, and height, with different types of refractive errors in a population of university students in the south of Iran.

Methods:

In this cross-sectional study, a number of university majors were selected as clusters using multi-stage sampling in all universities located in Kazerun (27 clusters of 133 clusters). Then, proportional to size, a number of students in each major were randomly selected to participate in the study. Uncorrected and corrected visual acuity, non-cycloplegic objective refraction and subjective refraction were measured in all participants.

Results:

The prevalence and 95% confidence interval (CI) of presenting visual impairment and blindness was 2.19% (1.48–3.23) and 0.27% (0.12–0.62), respectively. Refractive errors comprised 75% of the causes of visual impairment. The prevalence (95% CI) of myopia [spherical equivalent (SE) ≤ –0.5 D], hyperopia (SE ≥ 0.5 D), and astigmatism (cylinder power < –0.5 D) was 42.71% (39.71–45.77), 3.75% (2.85–4.51), and 29.46% (27.50–31.50), respectively. Totally, 49.03% (46.39–51.68) of the participants had at least one type of refractive error. There was a positive association between weight and myopia (1.01; 95% CI: 1.01–1.02), anisometropia (1.03; 95% CI: 1.01–1.06), and refractive errors (1.01; 95% CI: 1.01–1.02). In comparison with the age group 18–19 years, the odds ratio (OR) of astigmatism in the age group 26–27 years was 1.64 (95% CI: 1.03–2.61), and the OR of anisometropia in the age group ≥ 30 years was 0.21 (95% CI: 0.04–0.98).

Conclusions:

The prevalence of refractive errors, especially myopia, is higher in university students than the general population. Since refractive errors constitute a major part of visual impairment, university students should receive special services for providing corrective lenses and glasses to reduce the burden of these disorders.
Earth’s Rich Textures, Seen by Satellite
Authors: Cartier Kimberly
Published: September 2018

From the soaring peaks of the Himalayas to Baltic algae blooms, Earth-observing satellites showcase the breathtaking and seemingly tactile beauty of our planet.
Examining the Potential Contribution of the Hokusai Impact to Water Ice on Mercury
Authors: Ernst Carolyn M. , Chabot Nancy L. , Barnouin Olivier S.
Published: September 2018

The polar cold traps of Mercury host an estimated 1016–1018 g of water ice. The relative purity of the water‐ice deposits could indicate they were emplaced over a short time interval, and sharp albedo boundaries suggest that the water ice could have been emplaced relatively recently. Together, these lines of evidence are consistent with potential delivery by a single, large, young impact event. Hokusai is the most prominent large young impact crater on Mercury—if the bulk of Mercury's water‐ice inventory was indeed delivered by a single recent impact event, Hokusai is the best candidate source crater. This study constrains the impact conditions that created Hokusai from morphological and color observations of the crater and its ejecta. Results show that the Hokusai impact was recent and oblique. These parameters, coupled with retention and migration factors largely derived from existing lunar studies, are used to estimate the possible contribution of the Hokusai impact to water ice on Mercury. Assuming water‐rich asteroidal or cometary impactors, the Hokusai impact event could account for the inventory of water ice on Mercury for impact velocities less than ~30 km/s, a velocity that is achieved by 24–32% of impacts into Mercury, depending on the size distribution model employed. The single impact delivery scenario therefore remains viable for Mercury. Robust modeling of a single large impact event on Mercury would supply critical insight into the feasibility of this scenario.
Ecological Changes in the Nannoplankton Community Across A Shelf Transect During the Onset of the Paleocene‐Eocene Thermal Maximum
Authors: León y León Isabel A. , Bralower Timothy J. , Self‐Trail Jean M.
Published: September 2018

Warming and other environmental changes during the Paleocene‐Eocene thermal maximum (PETM) led to profound shifts in the composition and structure of nannoplankton assemblages. Here we analyze the nature of these changes in expanded records from the Cambridge‐Dorchester and Mattawoman Creek‐Billingsley Road cores in Maryland. These cores comprise part of a transect of five paleoshelf cores from Maryland and New Jersey. We integrate multivariate analysis of assemblage data with proxy data to revise understanding of the paleoecological affinities of key species. In particular, Discoaster and Fasciculithus are interpreted as thermophiles without adaptation to particular nutrient levels, while Hornibrookina is considered an opportunist adapted to highly variable nearshore environments. Together the cores show consistent margin‐wide changes across the onset of the PETM, including a pulse of preevent warming, possibly combined with lower salinity, high seasonality, or increased turbidity. The event itself was characterized by continued warming and eutrophication across the paleoshelf. The Maryland sites experienced higher environmental variability as a result of their proximity to large river systems.
Catalyst free hydrazone ligation for protein labeling and modification using electron-deficient benzaldehyde reagents
Authors: Xu Yang , Wang Yu , Liu Peiyuan , Chu Guo-Chao , Xu Huajian , Li Yi-Ming , Wang Jun , Shi Jing
Published: September 2018

We developed a novel electron-deficient benzaldehyde reagent for catalyst free hydrazone ligation.
Reinvestigation of the iodine-mediated phosphoramidation reaction of amines and P(OR)3 and its synthetic applications
Authors: Chen Xunwei , Xiao Zecai , Chu Hanyu , Wang Bo , Peng Ai-Yun
Published: September 2018

A convenient and effective iodine-mediated phosphoramidation reaction of amines and P(OR)3 has been provided.
Hydrogels based on pH-responsive reversible carbon–nitrogen double-bond linkages for biomedical applications
Authors: Zhang Zhen , He Chaoliang , Chen Xuesi
Published: September 2018

This review outlines recent progress of pH-responsive hydrogels based on condensation reactions between nucleophiles and carbonyl groups for biomedical applications.
Representations of chemical phenomena in secondary school chemistry textbooks
Authors: Enero Upahi Johnson , Ramnarain Umesh
Published: September 2018

The difficulties encountered by students in learning chemistry range from human factors to the intrinsic nature of chemistry. To enhance students’ understanding of chemistry, there is a wide consensus within the community of chemistry educators on the importance of and need to integrate different levels of representations in chemistry teaching and learning resources. As learning resources, textbooks are ubiquitous and usually readily available to both students and teachers. Therefore, this study investigated how chemical phenomena are represented or depicted in secondary school chemistry textbooks. We adopted a rubric developed by Gkitziaet al.(Gkitzia V., Salta K. and Tzougraki C., (2011), Development and application of suitable criteria for the evaluation of chemical representations in school textbooks,Chem. Educ. Res. Pract.,12, 5–14) to analyze the textbooks for types of representations; relatedness of chemical representations to text; and the appropriateness of captions. The results indicated the dominance of symbolic representations, followed by sub-microscopic, then hybrid and multiple representations. In all three textbooks, there was no evidence of mixed representation. While many of the chemical representations were completely related to the texts, some were unlinked. The germaneness of suitable captions in textbooks is in the explicit, brief and concise explanation that captions give to an entire representation. While our results indicated that more than half of the representations had suitable captions, there was evidence of representations that were problematic and had no captions. The implication of these results for students’ cognitive load, and the need for textbook-users to explore alternative resources that depict phenomena in 2D or 3D representations are discussed.
Exploring the effects of intercluster torsion stress on Mn2+-related red emission from cluster-based layered metal chalcogenides
Authors: Xu Xiaofan , Hu Dandan , Xue Chaozhuang , Zhang Jiaxu , Li Dong-Sheng , Wu Tao
Published: September 2018

Intercluster torsion stress exhibits a dramatic effect on Mn2+-related red emission from cluster-based layered metal chalcogenides.
Multi‐dimensional encryption scheme based on physical layer for fading channel
Authors: Huang Ying , Lei Jing , El‐Hajjar Mohammed , Li Wei
Published: September 2018

In order to solve the security problem for fading channel, a pragmatic physical layer encryption (PLE) scheme is proposed, which utilises diversity technique elaborately. Different from the conventional PLE schemes based on phase rotation for the modulated symbol, the proposed scheme changed phase and amplitude together for a block of symbols each time, which can be defined as multi‐dimensional PLE (MPLE). Unconventional constellation obfuscates eavesdropper, which can be seen as the first level security in the physical layer. The correct probability based on chosen plaintext attacks and known plaintext attacks is deduced. It can be seen from the simulation results that the MPLE scheme can achieve lower attack success probability because of multi‐level security and better performance based on diversity under fading channel.
Design of spiral slot‐based dual‐wideband dual‐sense CP antenna
Authors: Xu Rui , Li Jian‐Ying , Liu Jie , Zhou Shi‐Gang , Wei Kun
Published: September 2018

A dual‐wideband dual‐sense circularly polarised (CP) planar slot antenna with a simple structure is presented and studied in this study. By etching a simple spiral slot on the planar ground, adopting an L‐shaped strip as the radiator, and employing smooth transition structure, the dual‐wideband impedance bandwidths (IBWs) and dual‐wideband 3 dB axial‐ratio bandwidths (ARBWs) of the proposed CP antenna can be easily realised. The measured 10 dB return loss IBWs is 111.1% (0.88–3.08 GHz) for the lower band [left‐hand CP (LHCP)] and 42.1% (3.64–5.58 GHz) for the upper band [right‐hand CP (RHCP)]. The measured 3‐dB ARBWs is 92.9 and 39.4%, with respect to 1.83 GHz (LHCP) and 4.6 GHz (RHCP), respectively. The radiation patterns of this antenna are good within both two CP bands. This antenna is very suitable for multi‐band communication systems for its dual‐wideband CP performance.
Modular multilevel converter with modified half‐bridge submodule and arm filter for dc transmission systems with dc fault blocking capability
Authors: Ahmed Khaled H. , Adam Grain P. , Abdelsalam Ibrahim A. , Aboushady Ahmed A.
Published: September 2018

Although a modular multilevel converter (MMC) is universally accepted as a suitable converter topology for the high‐voltage dc transmission systems, its dc fault ride performance requires substantial improvement in order to be used in critical infrastructures such as transnational multi‐terminal dc (MTDC) networks. Therefore, this study proposes a modified submodule circuit for MMC that offers an improved dc fault ride through the performance with reduced semiconductor losses and enhanced control flexibility compared to that achievable with full‐bridge submodules. The use of the proposed submodules allows MMC to retain its modularity; with semiconductor loss similar to that of the mixed submodules MMC, but higher than that of the half‐bridge submodules. Besides dc fault blocking, the proposed submodule offers the possibility of controlling ac current in‐feed during pole‐to‐pole dc short‐circuit fault, and this makes such submodule increasingly attractive and useful for continued operation of MTDC networks during dc faults. The aforesaid attributes are validated using simulations performed in MATLAB/SIMULINK and substantiated experimentally using the proposed submodule topology on a four‐level small‐scale MMC prototype.
Cancellation of harmonic torque disturbance in permanent magnet synchronous motor drives by using an adaptive feedforward controller
Authors: Abou‐Qamar Nezar , Hatziadoniu Constantine
Published: September 2018

The effects of disruptive harmonic torque disturbances on permanent magnet synchronous motor drives originating at the mechanical load or from cogging can be mitigated by producing a counteracting electric torque. The study proposes using an adaptive feedforward controller (AFC) for this purpose. The AFC is designed to operate as an auxiliary loop in parallel with a field‐oriented controller, which provides speed control. The AFC input is the motor speed control error. The loop is tuned at the frequency of the harmonic torque and its output is added to the q‐axis current reference as a variation current of the same frequency. The main advantage of the proposed method is that it does not require an estimation of the disturbance torque. The theoretical analysis of the scheme is presented in the study. Experimental results are also presented in the study from a motor drive system where the mechanical load produces harmonic torques. The results demonstrate the effectiveness of the AFC in significantly reducing speed oscillations by cancelling the effect of the torque harmonic disturbance.
High step‐up dc–dc converter with multi‐winding CL and switched capacitor
Authors: Ye Yuanmao , Peng Wei , Jiang Bijia
Published: September 2018

To achieve a high‐voltage gain, a step‐up converter is developed by integrating coupled‐inductor (CL) and switched capacitor. Low‐voltage‐rated transistors are used to improve the efficiency as the voltage stress on the main switch of the proposed converter is reduced. Circuit configuration, operation principle, ideal voltage transfer ratio and switches’ stresses are analysed in detail. The converter's structure can be easily extended for ultra‐high‐voltage gain by increasing the number of windings of the CL. The feasibility of the proposed converter is experimentally demonstrated by a 140 W prototype converter.
Canal lock variable speed hydropower turbine design and control
Authors: Zhang Jian , Leontidis Vlasios , Dazin Antoine , Tounzi Abdelmounaim , Delarue Phillipe , Caignaert Guy , Piriou Francis , Libaux Antoine
Published: September 2018

The design of a novel submerged hydraulic turbine for producing electricity by converting the available hydropower on canal locks during raising and lowering ships, but with the minimum overall impact on the facility, is being considered. The hydraulic head in such applications is low (few metres) and varies over time (from its maximum value down to zero) resulting in a low potential conversion of hydraulic head in electrical energy. The study involves the modification of the hydraulic transient system, the design and performance estimation of a hydraulic turbine. Based on the performance curves, a permanent magnet Vernier generator is designed. The models of the hydraulic turbine and generator are added to the system model and simulation results of the whole system are presented.
Data‐driven predictive analytics of unexpected wind turbine shut‐downs
Authors: Man Jianing , Zhang Zijun , Zhou Qiang
Published: September 2018

In this study, a novel data‐driven framework is proposed to offer predictive analytics of wind turbine (WT) unexpected shut‐downs based on data collected by the supervisory control and data acquisition (SCADA) system. A new parameter, the remaining functional life (RFL), is introduced to describe the length of a period until the next WT shut‐down and a binary target parameter is created based on the RFL for indicating impending unexpected WT shut‐downs. A two‐stage data‐driven framework is proposed to develop the predictive analytics model of the unexpected WT shut‐downs based on SCADA data. The first stage employs clustering methods to automatically cluster WT SCADA data through unsupervised learning. In the second stage, based on clusters of SCADA data, famous classification methods are applied to develop models for inferring the binary target parameter. To validate the proposed data‐driven framework, case studies and intensive computational experiments are conducted. Computational results confirm that meaningful predictive analytics of unexpected WT shut‐downs can be produced through the proposed data‐driven framework.
Antarctica is not protected from an influx of new species
Authors: Miller Johanna L.
Published: September 2018

Nonnative organisms have the unexpected potential to colonize the southern polar region, according to an interdisciplinary study that combined DNA analysis and ocean-current dynamics.
Vibrational spectroscopy dissects a surface reaction
Authors: Miller Johanna L.
Published: September 2018

When a metal surface catalyzes a chemical process, each surface atom’s local environment matters.
Coffee stains, cell receptors, and time crystals: Lessons from the old literature
Authors: Goldstein Raymond E.
Published: September 2018

Perhaps the most important reason to understand the deep history of a field is that it is the right thing to do.
A novel bifunctional aspartate kinase-homoserine dehydrogenase from the hyperthermophilic bacterium, Thermotoga maritima
Authors: Ohshida Tatsuya , Koba Kohei , Hayashi Junji , Yoneda Kazunari , Ohmori Taketo , Ohshima Toshihisa , Sakuraba Haruhiko
Published: September 2018

The orientation of the three domains in the bifunctional aspartate kinase-homoserine dehydrogenase (AK-HseDH) homologue found in Thermotoga maritima totally differs from those observed in previously known AK-HseDHs; the domains line up in the order HseDH, AK, and regulatory domain. In the present study, the enzyme produced in Escherichia coli was characterized. The enzyme exhibited substantial activities of both AK and HseDH. l-Threonine inhibits AK activity in a cooperative manner, similar to that of Arabidopsis thaliana AK-HseDH. However, the concentration required to inhibit the activity was much lower (K0.5 = 37 μM) than that needed to inhibit the A. thaliana enzyme (K0.5 = 500 μM). In contrast to A. thaliana AK-HseDH, Hse oxidation of the T. maritima enzyme was almost impervious to inhibition by l-threonine. Amino acid sequence comparison indicates that the distinctive sequence of the regulatory domain in T. maritima AK-HseDH is likely responsible for the unique sensitivity to l-threonine.

Abbreviations: AK: aspartate kinase; HseDH: homoserine dehydrogenase; AK–HseDH: bifunctional aspartate kinase–homoserine dehydrogenase; AsaDH: aspartate–β–semialdehyde dehydrogenase; ACT: aspartate kinases (A), chorismate mutases (C), and prephenate dehydrogenases (TyrA, T).
Precision Lasso: accounting for correlations and linear dependencies in high-dimensional genomic data
Authors: Wang Haohan , Lengerich Benjamin J , Aragam Bryon , Xing Eric P
Published: September 2018

Motivation

Association studies to discover links between genetic markers and phenotypes are central to bioinformatics. Methods of regularized regression, such as variants of the Lasso, are popular for this task. Despite the good predictive performance of these methods in the average case, they suffer from unstable selections of correlated variables and inconsistent selections of linearly dependent variables. Unfortunately, as we demonstrate empirically, such problematic situations of correlated and linearly dependent variables often exist in genomic datasets and lead to under-performance of classical methods of variable selection.

Results

To address these challenges, we propose the Precision Lasso. Precision Lasso is a Lasso variant that promotes sparse variable selection by regularization governed by the covariance and inverse covariance matrices of explanatory variables. We illustrate its capacity for stable and consistent variable selection in simulated data with highly correlated and linearly dependent variables. We then demonstrate the effectiveness of the Precision Lasso to select meaningful variables from transcriptomic profiles of breast cancer patients. Our results indicate that in settings with correlated and linearly dependent variables, the Precision Lasso outperforms popular methods of variable selection such as the Lasso, the Elastic Net and Minimax Concave Penalty (MCP) regression.

Availability and implementation

Software is available at https://github.com/HaohanWang/thePrecisionLasso.

Supplementary information

Supplementary data are available at Bioinformatics online.
Bayesian integrative model for multi-omics data with missingness
Authors: Fang Zhou , Ma Tianzhou , Tang Gong , Zhu Li , Yan Qi , Wang Ting , Celedón Juan C , Chen Wei , Tseng George C
Published: September 2018

Motivation

Integrative analysis of multi-omics data from different high-throughput experimental platforms provides valuable insight into regulatory mechanisms associated with complex diseases, and gains statistical power to detect markers that are otherwise overlooked by single-platform omics analysis. In practice, a significant portion of samples may not be measured completely due to insufficient tissues or restricted budget (e.g. gene expression profile are measured but not methylation). Current multi-omics integrative methods require complete data. A common practice is to ignore samples with any missing platform and perform complete case analysis, which leads to substantial loss of statistical power.

Methods

In this article, inspired by the popular Integrative Bayesian Analysis of Genomics data (iBAG), we propose a full Bayesian model that allows incorporation of samples with missing omics data.

Results

Simulation results show improvement of the new full Bayesian approach in terms of outcome prediction accuracy and feature selection performance when sample size is limited and proportion of missingness is large. When sample size is large or the proportion of missingness is low, incorporating samples with missingness may introduce extra inference uncertainty and generate worse prediction and feature selection performance. To determine whether and how to incorporate samples with missingness, we propose a self-learning cross-validation (CV) decision scheme. Simulations and a real application on child asthma dataset demonstrate superior performance of the CV decision scheme when various types of missing mechanisms are evaluated.

Availability and implementation

Freely available on the GitHub at https://github.com/CHPGenetics/FBM

Supplementary information

Supplementary data are available at Bioinformatics online.
When a single lineage is not enough: Uncertainty-Aware Tracking for spatio-temporal live-cell image analysis
Authors: Theorell Axel , Seiffarth Johannes , Grünberger Alexander , Nöh Katharina
Published: September 2018

Motivation

Microfluidic platforms for live-cell analysis are in dire need of automated image analysis pipelines. In this context, producing reliable tracks of single cells in colonies has proven to be notoriously difficult without manual assistance, especially when image sequences experience low frame rates.

Results

With Uncertainty-Aware Tracking (UAT), we propose a novel probabilistic tracking paradigm for simultaneous tracking and estimation of tracking-induced errors in biological quantities derived from live-cell experiments. To boost tracking accuracy, UAT relies on a Bayesian approach which exploits temporal information on growth patterns to guide the formation of lineage hypotheses. A biological study is presented, in which UAT demonstrates its ability to track cells, with comparable to better accuracy than state-of-the-art trackers, while simultaneously estimating tracking-induced errors.

Availability and implementation

Image sequences and Java executables for reproducing the results are available at https://doi.org/10.5281/zenodo.1299526.

Supplementary information

Supplementary data are available at Bioinformatics online.
Differential methylation values in differential methylation analysis
Authors: Xie Changchun , Leung Yuet-Kin , Chen Aimin , Long Ding-Xin , Hoyo Catherine , Ho Shuk-Mei
Published: September 2018

Motivation

Both β-value and M-value have been used as metrics to measure methylation levels. The M-value is more statistically valid for the differential analysis of methylation levels. However, the β-value is much more biologically interpretable and needs to be reported when M-value method is used for conducting differential methylation analysis. There is an urgent need to know how to interpret the degree of differential methylation from the M-value. In M-value linear regression model, differential methylation M-value ΔM can be easily obtained from the coefficient estimate, but it is not straightforward to get the differential methylation β-value, Δβ since it cannot be obtained from the coefficient alone.

Results

To fill the gap, we have built a bridge to connect the statistically sound M-value linear regression model and the biologically interpretable Δβ. In this article, three methods were proposed to calculate differential methylation values, Δβ from M-value linear regression model and compared with the Δβ directly obtained from β-value linear regression model. We showed that under the condition that M-value linear regression model is correct, the method M-model-coef is the best among the four methods. M-model-M-mean method works very well too. If the coefficients α0, α2,…αp are not given (as ‘MethLAB’ package), the M-model-M-mean method should be used. The Δβ directly obtained from β-value linear regression model can give very biased results, especially when M-values are not in (−2, 2) or β-values are not in (0.2, 0.8).

Availability and implementation

The dataset for example is available at the National Center for Biotechnology Information Gene Expression Omnibus repository, GSE104778.

Supplementary information

Supplementary data are available at Bioinformatics online.
Efficiency Versus Equality in Bargaining
Authors: Galeotti Fabio , Montero Maria , Poulsen Anders
Published: September 2018

We consider how the outcome of bargaining varies with changes in the trade-off between equality, efficiency, and total-earnings maximization. We observe that subjects avoid an equal-earning outcome if it is Pareto inefficient; a large proportion of bargaining pairs avoids an equal and Pareto efficient outcome in favor of one giving unequal and total-earnings maximizing payoffs, and this proportion increases when unequal outcomes imply larger earnings to one of the players, even though this also implies higher inequality; finally, we document a compromise effect that violates the independence of irrelevant alternatives condition.
Pro: Tolvaptan delays the progression of autosomal dominant polycystic kidney disease
Authors: Torres Vicente E
Published: September 2018

No treatment until now has directly targeted the mechanisms responsible for the development and growth of cysts in autosomal dominant polycystic kidney disease (ADPKD). Strong rationale and preclinical studies using in vitro and in vivo models justified the launching of two large phase 3 clinical trials of tolvaptan in early and later stages of ADPKD. Their design was based on preliminary studies informing on the pharmacokinetics, pharmacodynamics, short-term safety and self-reported tolerability in patients with ADPKD. Tolvaptan slowed kidney growth in the early stage and estimated glomerular filtration rate decline in early and later stages of the disease. All participants had the opportunity to enroll in open-label extension trials to ascertain long-term safety and efficacy. In a single-center analysis of long-term outcomes, the effect of tolvaptan was sustained and cumulative over time supporting a disease-modifying effect of tolvaptan in ADPKD. In the countries where tolvaptan has been approved by regulatory agencies, patients with rapidly progressive ADPKD should be informed about the option of treatment including possible benefits and risks. If a decision to initiate treatment is made, prescribing physicians should educate the patients on the prevention of aquaresis-related adverse events and should be vigilant in the surveillance and management of the potential tolvaptan hepatotoxicity. Other vasopressin V2 receptor antagonists, possibly without potential hepatotoxicity, alternative strategies targeting vasopressin and combination with other drugs able to enhance the efficacy or reduce the aquaresis associated with tolvaptan, deserve further study.
Urinary soluble CD163 and monocyte chemoattractant protein-1 in the identification of subtle renal flare in anti-neutrophil cytoplasmic antibody-associated vasculitis
Authors: Moran Sarah M , Monach Paul A , Zgaga Lina , Cuthbertson David , Carette Simon , Khalidi Nader A , Koening Curry L , Langford Carol A , McAlear Carol A , Moreland Larry , Pagnoux Christian , Seo Philip , Specks Ulrich , Sreih Antoine , Wyse Jason , Ytterberg Steven R , Merkel Peter A , Little Mark A ,   for the Vasculitis Clinical Research Consortium
Published: September 2018

Background

Prior work has shown that urinary soluble CD163 (usCD163) displays excellent biomarker characteristics for detection of active renal vasculitis using samples that included new diagnoses with highly active renal disease. This study focused on the use of usCD163 in the detection of the more clinically relevant state of mild renal flare and compared results of usCD163 testing directly to testing of urinary monocyte chemoattractant protein-1 (uMCP-1).

Methods

Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV, n = 88) were identified within a serially sampled, longitudinal and multicentre cohort. Creatinine-normalized usCD163 and uMCP-1 levels were measured by enzyme-linked immunosorbent assay and, both alone and in combination, were compared between times of active renal AAV and during remission and/or active non-renal AAV.

Results

Samples from 320 study visits included times of active renal vasculitis (n = 39), remission (n = 233) and active extrarenal vasculitis (n = 48). Median creatinine levels were 0.9 mg/dL [interquartile range (IQR) 0.8–1.2] in remission and 1.4 mg/dL (IQR 1.0–1.8) during renal flare. usCD163 levels were higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 162 ng/mmol (IQR 79–337), 44 (17–104) and 38 (7–76), respectively (P < 0.001). uMCP-1 levels were also higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 10.6 pg/mmol (IQR 4.6–23.5), 4.1 (2.5–8.4) and 4.1 (1.9–6.8), respectively (P < 0.001). The proposed diagnostic cut-points for usCD163 and uMCP-1 were 72.9 ng/mmol and 10.0 pg/mmol, respectively. usCD163 and uMCP-1 levels were marginally correlated (r2 = 0.11, P < 0.001). Combining novel and existing biomarkers using recursive tree partitioning indicated that elevated usCD163 plus either elevated uMCP-1 or new/worse proteinuria improved the positive likelihood ratio (PLR) of active renal vasculitis to 19.2.

Conclusion

A combination of usCD163 and uMCP-1 measurements appears to be useful in identifying the diagnosis of subtle renal vasculitis flare.
Development of Machine Learning Algorithms for Prediction of 30-Day Mortality After Surgery for Spinal Metastasis
Authors: Karhade Aditya V , Thio Quirina C B S , Ogink Paul T , Shah Akash A , Bono Christopher M , Oh Kevin S , Saylor Phil J , Schoenfeld Andrew J , Shin John H , Harris Mitchel B , Schwab Joseph H
Published: September 2018

BACKGROUND

Preoperative prognostication of short-term postoperative mortality in patients with spinal metastatic disease can improve shared decision making around end-of-life care.

OBJECTIVE

To (1) develop machine learning algorithms for prediction of short-term mortality and (2) deploy these models in an open access web application.

METHODS

The American College of Surgeons, National Surgical Quality Improvement Program was used to identify patients that underwent operative intervention for metastatic disease. Four machine learning algorithms were developed, and the algorithm with the best performance across discrimination, calibration, and overall performance was integrated into an open access web application.

RESULTS

The 30-d mortality for the 1790 patients undergoing surgery for spinal metastatic disease was 8.49%. Preoperative factors used for prognostication were albumin, functional status, white blood cell count, hematocrit, alkaline phosphatase, spinal location (cervical, thoracic, lumbosacral), and severity of comorbid systemic disease (American Society of Anesthesiologist Class). In this population, machine learning algorithms developed to predict 30-d mortality performed well on discrimination (c-statistic), calibration (assessed by calibration slope and intercept), Brier score, and decision analysis. An open access web application was developed for the best performing model and this web application can be found here: https://sorg-apps.shinyapps.io/spinemets/.

CONCLUSION

Machine learning algorithms are promising for prediction of postoperative outcomes in spinal oncology and these algorithms can be integrated into clinically useful decision tools. As the volume of data in oncology continues to grow, creation of learning systems and deployment of these systems as accessible tools may significantly enhance prognostication and management.
Childhood locus of control and self-esteem, education, psychological distress and physical exercise as predictors of adult obesity
Authors: Cheng Helen , Furnham Adrian
Published: September 2018

Objective

To investigate to what extent locus of control, self-esteem, psychological distress, physical exercise, as well as socio-demographic factors are associated with obesity in 42-year-old adults in a longitudinal birth cohort study.

Method

The sample consisted of 5645 participants born in Great Britain in 1970 and followed up at 10, 34 and 42 years with data on body mass index measured at 34 and 42 years.

Results

There was an increase of adult obesity from 15.5% at age 34 to 21.2% at 42 years. Locus of control and self-esteem measured at age 10 years, psychological distress and educational qualifications assessed at age 34, and current occupational levels and physical exercise were all significantly associated with adult obesity at age 42. The associations remained significant after controlling for birth weight and gestation, maternal and paternal BMI, childhood BMI, and intelligence.

Conclusion

Childhood locus of control and self-esteem, educational qualifications, psychological distress and physical exercise were all significantly and independently associated with adult obesity.
The Effect of Product Misperception on Economic Outcomes: Evidence from the Extended Warranty Market
Authors: Abito Jose Miguel , Salant Yuval
Published: September 2018

Panel and experimental data are used to analyse the economic outcomes in the extended warranty market. We establish that the strong demand and high profits in this market are driven by consumers distorting the failure probability of the insured product, rather than standard risk aversion or sellers’ market power. Providing information to consumers about failure probabilities significantly reduces their willingness to pay for warranties, indicating the important role of information, or lack of, in driving consumers’ purchase behaviour. Such information provision is shown to be more effective in enhancing consumer welfare than additional market competition.
In silicoprediction of high-resolution Hi-C interaction matrices
Authors: Zhang Shilu , Chasman Deborah , Knaack Sara , Roy Sushmita
Published: September 2018

The three-dimensional organization of the genome plays an important role in gene regulation by enabling distal sequence elements to control the expression level of genes hundreds of kilobases away. Hi-C is a powerful genome-wide technique to measure the contact count of pairs of genomic loci needed to study three-dimensional organization. Due to experimental costs high resolution Hi-C datasets are available only for a handful of cell lines. Computational prediction of Hi-C contact counts can offer a scalable and inexpensive approach to examine three-dimensional genome organization across many cellular contexts. Here we present HiC-Reg, a novel approach to predict contact counts from one-dimensional regulatory signals such as epigenetic marks and regulatory protein binding. HiC-Reg exploits the signal from the region spanning two interacting regions and from across multiple cell lines to generalize to new contexts. Using existing feature importance measures and a new matrix factorization based approach, we found CTCF and chromatin marks, especially repressive and elongation marks, as important for predictive performance. Predicted counts from HiC-Reg identify topologically associated domains as well as significant interactions that are enriched for CTCF bi-directional motifs and agree well with interactions identified from complementary long-range interaction assays. Taken together, HiC-Reg provides a powerful framework to generate high-resolution profiles of contact counts that can be used to study individual locus level interactions as well as higher-order organizational units of the genome.
Asymmetrical endothelial cell migration from in vitro Quarter‐Descemet membrane endothelial keratoplasty grafts
Authors: Miron Alina , Spinozzi Daniele , Bruinsma Marieke , Lie Jessica T. , Birbal Rénuka S. , Baydoun Lamis , Oellerich Silke , Melles Gerrit R.J.
Published: September 2018

Purpose

To investigate in vitro central and peripheral corneal endothelial cell (EC) migration from Quarter–Descemet membrane endothelial keratoplasty (Quarter‐DMEK) grafts.

Methods

Quarter‐DMEK grafts were obtained from 10 corneas ineligible for transplantation but with intact and viable ECs. Ten Quarter‐DMEK grafts were ‘sandwiched’ between two glass slides and cultured over 1 week in a humidified atmosphere at 37 °C and 5% CO2. Cell migration was evaluated by light microscopy at standardized time intervals. In addition, immunohistochemistry analyses were performed to assess the detailed structural organization of ECs in the corneal centre and far periphery.

Results

Endothelial cell (EC) migration occurred from the radial cut graft edges, but not from the far peripheral area. Cell migration followed three different migration patterns: (1) individual cell migration, (2) uncoordinated cell migration of cell clusters and (3) collective migration in which ECs moved as a sheet. Immunostaining showed the presence of ECs up to the far periphery but with different expression patterns of phenotypical markers ZO‐1, Na+/K+ ‐ATPase and vimentin compared to central ECs.

Conclusion

In vitro EC migration from Quarter‐DMEK grafts occurs along the radial cut edges with a decrease in migration activity towards the corneal far periphery. No migration occurred along the outer peripheral corneal edge possibly due to a different anatomical matrix in the far periphery. Hence, ECs from the far periphery may not contribute to corneal clearance of the adjacent bare area after Quarter‐DMEK surgery, but these cells may constitute a valuable cellular reserve on the graft.