bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of differential plasma miRNA profiles in Chinese workers with occupational lead exposure
Authors: Xu Ming , Yu Zhengmin , Hu Feifei , Zhang Hongbing , Zhong Lixin , Han Lei , An Yan , Zhu Baoli , Zhang Hengdong
Published: September 2017

Elevated lead absorptions are hazardous factors in lead-related workers. Previous studies have found its toxic impacts on nervous, circulatory, and metabolic systems. We hypothesized that alteration of miRNAs profile in plasma was closely associated with lead exposure. We analyzed to identify lead-related miRNAs in workers occupationally exposed to lead. Microarray assay was performed to detect plasma miRNA between workers with high and minimal lead exposure in the discovery stage. The following prediction of miRNAs’ candidate target genes was carried out by using miRecords, STRING, and KEGG databases. We finally identified four miRNAs significantly associated with high level of blood lead. miR-520c-3p (*P=0.014), miR-211 (*P=0.019), and miR-148a (*P=0.031) were downexpressed in workers with high lead exposure and with high blood lead level (BLL), while miR-572(*P=0.027) displayed an opposite profile. Functional analysis of miRNAs displayed that these miRNAs could trigger different cellular genes and pathways. People under chronic lead exposure had a diverse ‘fingerprint’ plasma miRNA profile. Our study suggested that miR-520c-3p, miR-211, miR-148a, and miR-572 were the potential biomarkers for lead susceptibility in Chinese.
RNA structure prediction: from 2D to 3D
Authors: Thiel Bernhard C. , Flamm Christoph , Hofacker Ivo L.
Published: September 2017

We summarize different levels of RNA structure prediction, from classical 2D structure to extended secondary structure and motif-based research toward 3D structure prediction of RNA. We outline the importance of classical secondary structure during all those levels of structure prediction.
The regulatory status of gene-edited agricultural products in the EU and beyond
Authors: Custers René
Published: September 2017

Governments all over the world are struggling with the regulatory status of gene-edited organisms. Are they regulated? Should they be regulated? In the present paper, the main focus is on the regulatory status of gene-edited organisms within the European regulatory framework. A stepwise analysis is performed that comes to the conclusion that gene-edited agricultural products that carry edits that can also occur naturally by mating and/or natural recombination are not a genetically modified organism. On the question whether they should be regulated, it is argued that it is difficult to require regulatory oversight that would go beyond what we now require for conventional products that can carry the same types of alterations. A regulatory approach is pleaded for that abides to fundamental principles of law making, and which allows for gene editing to develop responsibly.
Decentralised voltage control with built‐in incentives for participants in distribution networks
Authors: Wang Xiaoxue , Wang Chengshan , Xu Tao , Guo Lingxu , Fan Shixiong , Wei Zechen
Published: September 2017

In the face of unprecedented challenges in environmental sustainability and grid resiliency, there is an increasingly held consensus regarding the adoption of distributed and renewable energy resources such as microgrids (MGs).This study explores a decentralised voltage control method based on a multi‐agent system (MAS) with built‐in incentives for various participants in distribution networks (DNs). Without an arbitration agent in MAS, peer agents calculate voltage sensitivities via agents’ local and neighbourhood measurements in a fully decentralised approach. An incentive mechanism is designed to motivate the MGs in DNs to participate in voltage control with guaranteed subsidies to ensure individual rationality. On the basis of the voltage sensitivities, each MG decides its strategy by managing energy suppliers and consumers to maximise its own profit while providing the ancillary service of voltage control. The strategy converges through an iterative process to a Nash equilibrium which maximises each MG's profit. In addition, an incomplete information game is applied to ensure the privacy of MGs. Furthermore, the feasibility and effectiveness of the proposed voltage control method is demonstrated on a modified IEEE 33‐bus system, and finally the existence of a Nash equilibrium in the game model is proved in the Appendix.
Analysis of efficiency improvement in wireless power transfer system
Authors: Liu Xin , Wang Tianfeng , Yang Xijun , Tang Houjun
Published: September 2017

Recently, efficiency improvement of wireless power transfer (WPT) systems has been the focus of research. Conventional methods of DC–DC converters are employed for load modulation to achieve high efficiency over large variations in mutual inductance and load. However, these additional circuits degrade the performance due to their inherent losses. To address this problem, this study presents a dual‐side phase shift control method for load modulation and voltage regulation in a compact WPT system. The key features of the proposed work are: attaining load modulation and voltage regulation with reduced size of the system; elimination of communication between active bridges and simple control logic. Mathematical expression of equivalent resistance versus the phase shift angles (PSAs) is deduced and the optimal PSAs for maximum efficiency are presented. Utilisation of local control, stability analysis and fault detection method are included. MATLAB/Simulink simulation and experimental results are carried out to validate the proposed method.
Asymptotically stable controller for SSTs based on Lyapunov direct stability method
Authors: Beiranvand Hamzeh , Rokrok Esmaeel
Published: September 2017

An asymptotically stable controller for solid‐state transformers (SSTs) based on Lyapunov direct stability (LDS) method is presented in this study. The proposed controller has four control objectives for the SST application, which includes unity power factor at medium‐voltage AC (VAC) side of the SST, constant DC‐link voltage and constant output voltage magnitude and frequency at low‐VAC side of the SST. To fulfil the above‐mentioned objectives four control laws are derived from the Lyapunov function, directly. The proposed LDS‐based controller is simulated using MATLAB/Simulink software. The obtained results indicate the fast and superior dynamic characteristics of the proposed controller. The LDS‐based controller is comprehensive and can be adopted for the SST applications.
Development process and analytical method of the pole‐to‐pole DC fault in the MMC‐MVDC system
Authors: Li Bo‐Tong , Liu Yi‐Chao , Li Bin , Zhang Yun‐Ke , Jia Jian‐Fei , Jing Fang‐Jie
Published: September 2017

Rapid rise of current and sudden drop of voltage at the DC side caused by a pole‐to‐pole DC fault in the modular multi‐level converter medium voltage direct current (MMC‐MVDC) transmission system seriously threaten the normal operation of the system. This study analyses the development process of the fault and studies the analytical method of the fault transient process. The study is structured as follows: the pre‐blocking equivalent circuit model is first proposed, involving the impact of the AC system and the dynamic switching of MMC submodules. Then the solving method of the state equations of fault current in each part of the converter is studied. Combined with the equivalent circuit model after the MMC is blocked, the solving method of state equations of fault current is proposed, with the non‐linearity of diodes considered. Finally, an MMC‐MVDC system model is built in PSCAD/EMTDC and fault simulations are carried out, verifying the correctness of the equivalent circuit and the accuracy of the fault current solving method.
Use of Rheumatic Scores to Guide Therapeutic Decisions in Patients with Ankylosing Spondylitis: Results of a Multicentre Study in Germany
Authors: Hillebrecht C. , Wolff B. , Kleine H. , Baerwald C. , Kuipers J.
Published: September 2017

Summary Background Rheumatology practice has seen an increasing development and use of scores to assess disease activity, loss of physical function, quality of life and radiographic damage. Study results, in particular for rheumatoid arthritis, demonstrate that target-oriented treatment concepts using scores lead to improved treatment results (Treat-to-Target).

Objective To review how frequently scores are used in daily rheumatological practice to assess disease activity, loss of physical function and treatment response in patients with ankylosing spondylitis and how much treatment decisions are influenced by the use of these scores.

Methods A Germany-wide prospective multicentre study 74 sites (61 rheumatologists in private practice and 13 hospital-based rheumatologists) documented the use of scores for assessing disease activity, treatment response, quality of life and imaging results in patients with ankylosing spondylitis (AS) (18–83 years) over 3 consecutive visits. A total of 1 476 fully evaluable visits of 492 patients [326 (66.26%) men and 166 (33.74%) women] were recorded.

Results The most commonly used scores were BASDAI (n=1.134, 84% of all visits) and BASFI (n=500, 37.5%). At least one score was calculated in 1.335 visits (90.45%); a combination of several scores was calculated in 748 visits (50.68%). Only in 141 visits (9.55%) no scores were calculated at all. Scores were used independently of patients’ age, duration of treatment, medication, and treatment changes and region of the participating rheumatologist. Scores recording treatment response (ASAS response) or quality of life were recorded in a few cases only. The average influence of a score on a treatment decision was 5.67 on a scale from 0 to 10.
Nonlinear viscous higher harmonics generation due to incident and reflecting internal wave beam collision
Authors: Aksu Anil A.
Published: September 2017

In this paper, we have considered the non-linear effects arising due to the collision of incident and reflected internal wave beams. It has already been shown analytically [Tabaei et al., “Nonlinear effects in reflecting and colliding internal wave beams,” J. Fluid Mech. 526, 217–243 (2005)] and numerically [Rodenborn et al., “Harmonic generation by reflecting internal waves,” Phys. Fluids 23, 026601 (2011)] that the internal wave beam collision generates the higher harmonics and mean flow in a linear stratification. In this paper, similar to previous analytical work, small amplitude wave theory is employed; however, it is formulated from energetics perspective which allows considering internal wave beams as the product of slowly varying amplitude and fast complex exponential. As a result, the mean energy propagation equation for the second harmonic wave is obtained. Finally, a similar dependence on the angle of incidence is obtained for the non-linear energy transfer to the second harmonic with previous analyses. A possible physical mechanism for this angle dependence on the second harmonic generation is also discussed here. In addition to previous studies, the viscous effects are also included in the mean energy propagation equation for the incident, the reflecting, and the second harmonic waves. Moreover, even though the mean flow obtained here is only confined to the interaction region, it is also affected by viscosity via the decay in the incident and the reflecting internal wave beams. Furthermore, a framework for the non-linear harmonic generation in non-linear stratification is also proposed here.
Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest
Authors: Mills Richard J. , Titmarsh Drew M. , Koenig Xaver , Parker Benjamin L. , Ryall James G. , Quaife-Ryan Gregory A. , Voges Holly K. , Hodson Mark P. , Ferguson Charles , Drowley Lauren , Plowright Alleyn T. , Needham Elise J. , Wang Qing-Dong , Gregorevic Paul , Xin Mei , Thomas Walter G. , Parton Robert G. , Nielsen Lars K. , Launikonis Bradley S. , James David E. , Elliott David A. , Porrello Enzo R. , Hudson James E.
Published: September 2017

Significance

Engineered cardiac muscle can be used to promote the structural and functional maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). However, previous studies have not yet produced cardiac tissues with metabolic and proliferative maturation. Here, we develop a 96-well screening platform and screen for cardiac maturation conditions in engineered cardiac muscle. We found that simulating the postnatal switch in metabolic substrates from carbohydrates to fatty acids promoted a switch in metabolism, DNA damage response, and cell cycle arrest in hPSC-CM. Our study shows that this mechanism can be harnessed to enhance the maturation of human hPSC-CM and cardiac tissues, which has major implications for stem cell sciences, drug discovery, and regenerative medicine.
IL-4–producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases
Authors: Hurdayal Ramona , Ndlovu Hlumani H. , Revaz-Breton Mélanie , Parihar Suraj P. , Nono Justin Komguep , Govender Melissa , Brombacher Frank
Published: September 2017

Significance

Cutaneous leishmaniasis and schistosomiasis are neglected tropical diseases for which there are no effective vaccines and limited treatment strategies. To develop vaccine and therapeutic alternatives, a detailed understanding of host immunity is essential. We show a role for IL-4Rα–responsive B cells in host susceptibility toLeishmania majorand protection againstSchistosoma mansoniinfection through the production of early IL-4, which in turn regulates Th2 cell polarization and disease outcome in mice. These important findings highlight the significant impacts that B cell-specific IL-4Rα and IL-4 responsiveness have in the context of type 1 (L. major) and type 2 (S. mansoni) pathogens. Thus, vaccine and therapeutic development should aim to target both B and T cell immunity for optimal efficacy.
Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant
IDH1
Authors: Mazor Tali , Chesnelong Charles , Pankov Aleksandr , Jalbert Llewellyn E. , Hong Chibo , Hayes Josie , Smirnov Ivan V. , Marshall Roxanne , Souza Camila F. , Shen Yaoqing , Viswanath Pavithra , Noushmehr Houtan , Ronen Sabrina M. , Jones Steven J. M. , Marra Marco A. , Cairncross J. Gregory , Perry Arie , Nelson Sarah J. , Chang Susan M. , Bollen Andrew W. , Molinaro Annette M. , Bengtsson Henrik , Olshen Adam B. , Weiss Samuel , Phillips Joanna J. , Luchman H. Artee , Costello Joseph F.
Published: September 2017

Significance

Identifying the drivers of tumorigenesis provides insight into mechanisms of transformation and can suggest novel therapeutic targets.
IDH1
mutations in gliomas are one such promising target. Drivers of tumor initiation may be distinct from those at tumor recurrence, however. Here, we demonstrate that in a subset of initially
IDH1
mutant gliomas
IDH1
is deleted or amplified at recurrence, yielding a higher grade tumor with a reprogrammed epigenome. We also report systematic selection for cells with
IDH1
CNA in vitro and in vivo. Thus, while
IDH1
mutation likely initiates gliomagenesis, neither mutant IDH1 nor the oncometabolite 2HG that it produces are required at recurrence. These findings have important implications for emerging therapeutic strategies targeting mutant IDH1.
Structure and orientation relationship of new precipitates in a Cu–Cr–Zr alloy
Authors: Chen Xiaobo , Jiang Feng , Liu Lele , Huang Hongfeng , Shi Zhangzhi
Published: September 2017

The crystallography and morphology of the nano-sized precipitate particles in a ternary Cu–Cr–Zr alloy were studied by transmission electron microscopy. A new type of face-centred-cubic (f.c.c) Cr-rich precipitate was observed. This precipitate is ordered and solute enriched on alternate {110} f.c.c planes, with an ellipsoid-shaped morphology. The new orientation relationship (OR) between the precipitate and Cu matrix satisfies [211]M//[011]p and [100]M//[111]p, {-111}M//{200}p and {02-2}M//{02-2}p. The difference between this new OR and the Nishiyama–Wasserman OR between body-centred-cubic (b.c.c) Cr and the Cu matrix can be detailed by Δ g vectors in the diffraction patterns. Furthermore, the precipitation strengthening effect is increased greatly with the formation of these new precipitate particles when compared to binary Cu–Cr alloys.
Fatigue behaviour of Inconel 625 cold spray coatings
Authors: Cavaliere Pasquale , Perrone Angelo , Silvello Alessio
Published: September 2017

Cold spray coatings were produced with Inconel 625 powders sprayed on a heat-treated Inconel 718 substrate. The processing parameters were varied to analyse the microstructural and mechanical variations as a function of cold spray conditions. Cold spray can contribute to improve the fatigue properties of repaired components; the best process conditions, leading to low porosity and high adhesion strength, were employed to produce coatings in notched samples to evaluate the fatigue crack behaviour of the sprayed material. The coatings were heat treated to evaluate the material microstructural evolution and mechanical properties. The crack initiation and growth behaviour of the coatings was studied also for the solution and precipitation hardening heat treatment condition to compare the fatigue behaviour with that belonging to the as sprayed one. It was demonstrated that the heat treatment has a beneficial effect on fatigue cracks retardation.
FMtree: a fast locating algorithm of FM-indexes for genomic data
Authors: Cheng Haoyu , Wu Ming , Xu Yun
Published: September 2017

Motivation

As a fundamental task in bioinformatics, searching for massive short patterns over a long text has been accelerated by various compressed full-text indexes. These indexes are able to provide similar searching functionalities to classical indexes, e.g. suffix trees and suffix arrays, while requiring less space. For genomic data, a well-known family of compressed full-text indexes, called FM-indexes, presents unmatched performance in practice. One major drawback of FM-indexes is that their locating operations, which report all occurrence positions of patterns in a given text, are not efficient, especially for the patterns with many occurrences.

Results

In this paper, we introduce a novel locating algorithm, FMtree, to fast retrieve all occurrence positions of any pattern via FM-indexes. When searching for a pattern over a given text, FMtree organizes the search space of the locating operation into a conceptual multiway tree. As a result, multiple occurrence positions of this pattern can be retrieved simultaneously by traversing the multiway tree. Compared with existing locating algorithms, our tree-based algorithm reduces large numbers of redundant operations and presents better data locality. Experimental results show that FMtree is usually one order of magnitude faster than the state-of-the-art algorithms, and still memory-efficient.

Availability and implementation

FMtree is freely available at https://github.com/chhylp123/FMtree.

Supplementary information

Supplementary data are available at Bioinformatics online.
Cyclotomic Discriminantal Arrangements and Diagram Automorphisms of Lie Algebras
Authors: Varchenko Alexander , Young Charles
Published: September 2017

We identify a class of affine hyperplane arrangements that we call cyclotomic discriminantal arrangements. We establish correspondences between the flag and Aomoto complexes of such arrangements and chain complexes for nilpotent subalgebras of Kac–Moody type Lie algebras with diagram automorphisms. As part of this construction, we find that flag complexes naturally give rise to a certain cocycle on the fixed-point subalgebras of such diagram automorphisms.

As a byproduct, we show that the Bethe vectors of cyclotomic Gaudin models associated to diagram automorphisms are nonzero. We also obtain the Poincare polynomial for the cyclotomic discriminantal arrangements.
Interpolating Sequences in Spaces with the Complete Pick Property
Authors: Aleman Alexandru , Hartz Michael , McCarthy John E , Richter Stefan
Published: September 2017

We characterize interpolating sequences for multiplier algebras of spaces with the complete Pick property. Specifically, we show that a sequence is interpolating if and only if it is separated and generates a Carleson measure. This generalizes results of Carleson for the Hardy space and of Bishop, Marshall, and Sundberg for the Dirichlet space. Furthermore, we investigate interpolating sequences for pairs of Hilbert function spaces.
Aerosol and boundary-layer interactions and impact on air quality
Authors: Li Zhanqing , Guo Jianping , Ding Aijun , Liao Hong , Liu Jianjun , Sun Yele , Wang Tijian , Xue Huiwen , Zhang Hongsheng , Zhu Bin
Published: September 2017

Air quality is concerned with pollutants in both the gas phase and solid or liquid phases. The latter are referred to as aerosols, which are multifaceted agents affecting air quality, weather and climate through many mechanisms. Unlike gas pollutants, aerosols interact strongly with meteorological variables with the strongest interactions taking place in the planetary boundary layer (PBL). The PBL hosting the bulk of aerosols in the lower atmosphere is affected by aerosol radiative effects. Both aerosol scattering and absorption reduce the amount of solar radiation reaching the ground and thus reduce the sensible heat fluxes that drive the diurnal evolution of the PBL. Moreover, aerosols can increase atmospheric stability by inducing a temperature inversion as a result of both scattering and absorption of solar radiation, which suppresses dispersion of pollutants and leads to further increases in aerosol concentration in the lower PBL. Such positive feedback is especially strong during severe pollution events. Knowledge of the PBL is thus crucial for understanding the interactions between air pollution and meteorology. A key question is how the diurnal evolution of the PBL interacts with aerosols, especially in vertical directions, and affects air quality. We review the major advances in aerosol measurements, PBL processes and their interactions with each other through complex feedback mechanisms, and highlight the priorities for future studies.
Understanding Risks: Practitioner’s Perceptions of the Lottery of Mental Healthcare Available for Detainees in Custody
Authors: Williams Emma , Norman Jenny , Sondhi Arun
Published: September 2017

The range and growing number of healthcare requirements being presented within custody environments has been widely debated (Rekrut-Lapa, T. and Lapa, A. (2014). ‘Health Needs of Detainees in Police Custody in England and Wales: Literature Review’. Journal of Forensic and Legal Medicine 69–75). Despite a number of reforms following the recommendations of the Bradley Review (Bradley (2009). Lord Bradley’s Review of People with Mental Health Problems or Learning Disabilities in the Criminal Justice System. Department of Health and Ministry of Justice) and the amendments made to the ACPO guidance on safe detention in 2012, research continues to highlight a lack of consistency to services available to effectively identify the needs of individuals in these arenas. This article is based on part of a wider research project conducted in the Metropolitan Police Service and portrays the voice of the police practitioners working in custody suites. The research found that various notions of risk are central within this setting and that current practices are not sufficient for ensuring the safety of both detainees and officers. The research concludes by offering a proposal for capturing good practice and learning in order to create a more reflective and learning environment in custody suites.
ATR is a multifunctional regulator of male mouse meiosis
Authors: Widger Alexander , Mahadevaiah Shantha K , Lange Julian , Ellnati Elias , Zohren Jasmin , Hirota Takayuki , Stanzione Marcello , Ojarikre Obah , Maciulyte Valdone , de Rooij Dirk , Tóth Attila , Keeney Scott , Turner James MA
Published: September 2017

Meiotic cells undergo genetic exchange between homologous chromosomes through programmed DNA double-strand break (DSB) formation, recombination and synapsis1, 2. In mice, the DNA damage-regulated phosphatidylinositol-3-kinase-like kinase (PIKK) ATM regulates all of these processes3-6. However, the meiotic functions of another major PIKK, ATR, have remained elusive, because germ line-specific depletion of this kinase is challenging. Using an efficient conditional strategy, we uncover roles for ATR in male mouse prophase I progression. Deletion of ATR causes chromosome axis fragmentation and germ cell elimination at mid pachynema. ATR is required for homologous synapsis, in a manner genetically dissociable from DSB formation. In addition, ATR regulates loading of recombinases RAD51 and DMC1 to DSBs and maintenance of recombination foci on synapsed and asynapsed chromosomes. Mid pachytene spermatocyte elimination in ATR deficient mice cannot be rescued by deletion of ATM and the third DNA damage-regulated PIKK, PRKDC, consistent with the existence of a PIKK-independent surveillance mechanism in the mammalian germ line. Our studies identify ATR as a multifunctional regulator of mouse meiosis.
Evaluation of Metrics for Benchmarking Antimicrobial Use in the United Kingdom Dairy Industry
Authors: Mills Harriet L. , Turner Andrea , Morgans Lisa , Massey Jonathan , Schubert Hannah , Rees Gwen , Broadfoot Fraser , Barrett David , Dowsey Andrew , Reyher Kristen K.
Published: September 2017

The issue of antimicrobial resistance is of global concern across human and animal health. In 2016 the UK government committed to new targets for reducing antimicrobial use (AMU) in livestock. However, though a number of metrics for quantifying AMU are defined in the literature, all give slightly different interpretations.

This paper reviews a selection of metrics for AMU in the dairy industry: total mg, total mg/kg, daily dose and daily course metrics. Although the focus is on their application to the dairy industry, the metrics and issues discussed are relevant across livestock sectors.

In order to be used widely, a metric should be understandable and relevant to the veterinarians and farmers who are prescribing and using antimicrobials. This means that clear methods, assumptions (and possible biases), standardised values and exceptions should be published for all metrics. Particularly relevant are assumptions around the number and weight of cattle at risk of treatment and definitions of dose rates and course lengths; incorrect assumptions can mean metrics over- or under-represent AMU.

The authors recommend that the UK dairy industry work towards UK-specific metrics using UK-specific medicine dose and course regimens as well as cattle weights in order to monitor trends nationally.
Ceasing the use of the highest priority critically important antimicrobials does not adversely affect production, health or welfare parameters in dairy cows
Authors: Turner Andrea , Tisdall David , Barrett David C. , Wood Sarah , Dowsey Andrew , Reyher Kristen K.
Published: September 2017

Due to scientific, public and political concern regarding antimicrobial resistance (AMR), several EU countries have already taken steps to reduce antimicrobial (AM) usage in production animal medicine, particularly that of the highest priority critically important AMs (HP-CIAs). While veterinarians are aware of issues surrounding AMR, barriers to change such as concerns of reduced animal health, welfare or production may inhibit AM prescribing changes.

Farmers from seven dairy farms in South West England engaged in changing AM use through an active process of education and herd health planning meetings. Prescribing data was collected from veterinary sales records; production and health data were accessed via milk recording and farm-recorded data.

This study demonstrates that cattle health and welfare - as measured by production parameters, fertility, udder health, mobility data and culling rates - can be maintained and even improved alongside a complete cessation in the use of HP-CIAs as well as an overall reduction of AM use on dairy farms.

This study also identified a need to consider different metrics when analysing AM use data, including dose-based metrics as well as those of total quantities to allow better representation of the direction and magnitude of changes in AM use.
Optimization-based synthesis of stochastic biocircuits with statistical specifications
Authors: Sakurai Yuta , Hori Yutaka
Published: September 2017

Model-guided design has become a standard approach to engineering biomolecular circuits in current synthetic biology. However, the stochastic nature of biomolecular reactions is often overlooked in the design process. As a result, cell-cell heterogeneity causes unexpected deviation of biocircuit behaviors from model predictions and requires additional iterations of design-build-test cycles. To enhance the design process of stochastic biocircuits, this paper presents a computational framework to systematically specify the level of intrinsic noise using well-defined metrics of statistics and design highly heterogeneous biocircuits based on the specifications. Specifically, we use descriptive statistics of population distributions as an intuitive specification language of stochastic biocircuits and develop an optimization based computational tool that explores parameter configurations satisfying design requirements. Sensitivity analysis methods are also developed to ensure the robustness of a biocircuit design. These design tools are formulated using convex optimization programs to enable efficient and rigorous quantification of the statistics without approximation, and thus, they are amenable to the synthesis of stochastic biocircuits that require high reliability. We demonstrate these features by designing a stochastic negative feedback biocircuit that satisfies multiple statistical constraints. In particular, we use a rigorously quantified parameter map of feasible design space to perform in-depth study of noise propagation and regulation in negative feedback pathways.
Detecting and correcting for bias in Mendelian randomization analyses using gene-by-environment interactions
Authors: Spiller Wes , Slichter David , Bowden Jack , Davey Smith George
Published: September 2017

Background: Mendelian randomization has developed into an established method for strengthening causal inference and estimating causal effects, largely due to the proliferation of genome-wide association studies. However, genetic instruments remain controversial as pleiotropic effects can introduce bias into causal estimates. Recent work has highlighted the potential of gene-environment interactions in detecting and correcting for pleiotropic bias in Mendelian randomization analyses.
Methods: We introduce MR using Gene-by-Environment interactions (MRGxE) as a framework capable of identifying and correcting for pleiotropic bias, drawing upon developments in econometrics and epidemiology. If an instrument-covariate interaction induces variation in the association between a genetic instrument and exposure, it is possible to identify and correct for pleiotropic effects. The interpretation of MRGxE is similar to conventional summary Mendelian randomization approaches, with a particular advantage of MRGxE being the ability to assess the validity of an individual instrument.
Results: We investigate the effect of BMI upon systolic blood pressure (SBP) using data from the UK Biobank and the GIANT consortium using a single instrument (a weighted allelic score). We find MRGxE produces findings in agreement with MR Egger regression in a two-sample summary MR setting, however, association estimates obtained across all methods differ considerably when excluding related participants or individuals of non-European ancestry. This could be a consequence of selection bias, though there is also potential for introducing bias by using a mixed ancestry population. Further, we assess the performance of MRGxE with respect to identifying and correcting for horizontal pleiotropy in a simulation setting, highlighting the utility of the approach even when the MRGxE assumptions are violated.
Conclusions: By utilising instrument-covariate interactions within a linear regression framework, it is possible to identify and correct for pleiotropic bias, provided the average magnitude of pleiotropy is constant across interaction covariate subgroups.
HyDe: a Python Package for Genome-Scale Hybridization Detection
Authors: Blischak Paul D. , Chifman Julia , Wolfe Andrea D. , Kubatko Laura S.
Published: September 2017

The analysis of hybridization and gene flow among closely related taxa is a common goal for researchers studying speciation and phylogeography. Many methods for hybridization detection use simple site pattern frequencies from observed genomic data and compare them to null models that predict an absence of gene flow. The theory underlying the detection of hybridization using these site pattern probabilities exploits the relationship between the coalescent process for gene trees within population trees and the process of mutation along the branches of the gene trees. For certain models, site patterns are predicted to occur in equal frequency (i.e., their difference is 0), producing a set of functions calledphylogenetic invariants. In this paper we introduce HyDe, a software package for detecting hybridization using phylogenetic invariants arising under the coalescent model with hybridization. HyDe is written in Python, and can be used interactively or through the command line using pre-packaged scripts. We demonstrate the use of HyDe on simulated data, as well as on two empirical data sets from the literature. We focus in particular on identifying individual hybrids within population samples and on distinguishing between hybrid speciation and gene flow. HyDe is freely available as an open source Python package under the GNU GPL v3 on both GitHub (https://github.com/pblischak/HyDe) and the Python Package Index (PyPI:https://pypi.python.org/pypi/phyde).
The PAGE Study: How Genetic Diversity Improves Our Understanding of the Architecture of Complex Traits
Authors: Wojcik Genevieve L , Graff Mariaelisa , Nishimura Katherine K , Tao Ran , Haessler Jeffrey , Gignoux Christopher R , Highland Heather M , Patel Yesha M , Sorokin Elena P , Avery Christy L , Belbin Gillian M , Bien Stephanie A , Cheng Iona , Cullina Sinead , Hodonsky Chani J , Hu Yao , Huckins Laura M , Jeff Janina , Justice Anne E , Kocarnik Jonathan M , Lim Unhee , Lin Bridget M , Lu Yingchang , Nelson Sarah C , Park Sung-Shim L , Poisner Hannah , Preuss Michael H , Richard Melissa A , Schurmann Claudia , Setiawan Veronica W , Sockell Alexandra , Vahi Karan , Vishnu Abhishek , Verbanck Marie , Walker Ryan , Young Kristin L , Zubair Niha , Acuna-Alonso Victor , Ambite Jose Luis , Barnes Kathleen C , Boerwinkle Eric , Bottinger Erwin , Bustamante Carlos D , Caberto Christian , Canizales-Quinteroes Samuel , Conomos Matthew P , Deelman Ewa , Do Ron , Doheny Kimberly , Fernandez-Rhodes Lindsay , Fornage Myriam , Heiss Gerardo , Henn Brenna , Hindorff Lucia A , Jackson Rebecca D , Hailu Benyam , Laurie Cecelia A , Laurie Cathy C , Li Yuqing , Lin Dan-Yu , Moreno-Estrada Andres , Nadkarni Girish , Norman Paul , Pooler Loreall C , Reiner Alexander P , Romm Jane , Sabati Chiara , Sandoval Karla , Sheng Xin , Stahl Eli A , Stram Daniel O , Thornton Timothy A , Wassel Christina L , Wilkens Lynne R , Winkler Cheryl A , Yoneyama Sachi , Buyske Steven , Haiman Chris , Kooperberg Charles , Marchand Loic Le , Loos Ruth JF , Matise Tara C , North Kari E , Peters Ulrike , Kenny Eimear E , Carlson Christopher S
Published: September 2017

Summary/Abstract

Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development, and clinical guidelines. However, the dominance of European-ancestry populations in GWAS creates a biased view of the role of human variation in disease, and hinders the equitable translation of genetic associations into clinical and public health applications. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioral phenotypes in 49,839 non-European individuals. Using strategies designed for analysis of multi-ethnic and admixed populations, we confirm 574 GWAS catalog variants across these traits, and find 38 secondary signals in known loci and 27 novel loci. Our data shows strong evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts, and insights into clinical implications. We strongly advocate for continued, large genome-wide efforts in diverse populations to reduce health disparities.
The cost of heat waves and droughts for global crop production
Authors: Mehrabi Zia , Ramankutty Navin
Published: September 2017

Heat waves and droughts are a key risk to global crop production and quantifying the extent of this risk is essential for insurance assessment and disaster risk reduction. Here we estimate the cumulative production losses of six major commodity groups under both extreme heat and drought events, across 131 countries, over the time period of 1961-2014. Our results show substantial variation in national disaster risks that have hitherto gone unrecognised in regional and global average estimates. The most severe losses are represented by cereal losses in Angola (4.1%), Botswana (5.7%), USA (4.4%) and Australia (4.4%), oilcrop losses in Paraguay (5.5%), pulse losses in Angola (4.7%) and Nigeria (4.8%), and root and tuber losses in Thailand (3.2%). In monetary terms we estimate the global production loss over this period to be $237 billion US Dollars (2004-2006 baseline). The nations that incurred the largest financial hits were the USA ($116 billion), the former Soviet Union ($37 billion), India ($28 billion), China ($10.7 billion) and Australia ($8.5 billion USD). Our analysis closes an important gap in our understanding of the impacts of extreme weather events on global crop production and provides the basis for country relevant disaster risk reduction.
A New Evidence of Lubrication Hypothesis on Nephila pilipes Spider Silk Spinning
Authors: Wu Hsuan-Chen , Wu Shang-Ru , Yang Jen-Chang
Published: September 2017

In spite of all the efforts on deciphering such spinning process of spiders, the underlying mechanism currently is yet to be fully revealed. In this research, we designed a novel approach to quantitatively estimate the overall concentration change of spider silk along the progression of liquid-to-solid silk transition from the gland silk. As a prior characterization, we first studied the influence of silking-rate, ranged from 1.5 to 8.0 m/min, on spun fiber diameters as well as fiber strengths. Furthermore, the liquid contents of silk in the sac and the silk fibers leaving the spinneret were investigated by thermogravimetric analysis (TGA) and by estimating the ratio of collected dried silk to the weight loss of spider, respectively. The strength of spun silk fiber showed in the range of 7.5 - 8.5 g/denier; while, the fiber diameter of 0.7 - 1.1 deniers for spun silk first increased then decreased with take-up speed of winder. The results showed that the percentage liquid content of silk stored in the major ampullate sac (50.0 wt%) was lower than that of silk leaving the spinnerets (80.9 - 96.1 wt%), indicating a liquid supplying mechanism might be involved during the spinning process. Thus, a hypothesis of liquid coating on the outer surface of the silk thread served as a lubrication layer to reduce the silking resistance in spinning spigot of spider was proposed. In addition, we speculated the spigot serves as a valve-like regulator that controls not only the fiber diameter but also the lubrication layer. These findings provide understanding in physiological function of the spider spinning process and could further shed some light on future biomimetic development of silk material fabrication.
Selenzyme: Enzyme selection tool for pathway design
Authors: Carbonell Pablo , Wong Jerry , Swainston Neil , Takano Eriko , Turner Nicholas J. , Scrutton Nigel S. , Kell Douglas B. , Breitling Rainer , Faulon Jean-Loup
Published: September 2017

Synthetic biology applies the principles of engineering to biology in order to create biological functionalities not seen before in nature. One of the most exciting applications of synthetic biology is the design of new organisms with the ability to produce valuable chemicals including pharmaceuticals and biomaterials in a greener; sustainable fashion. Selecting the right enzymes to catalyze each reaction step in order to produce a desired target compound is, however, not trivial. Here, we present Selenzyme, a free online enzyme selection tool for metabolic pathway design. The user is guided through several decision steps in order to shortlist the best candidates for a given pathway step. The tool graphically presents key information about enzymes based on existing databases and tools such as: similarity of sequences and of catalyzed reactions; phylogenetic distance between source organism and intended host species; multiple alignment highlighting conserved regions, predicted catalytic site, and active regions; and relevant properties such as predicted solubility and transmembrane regions. Selenzyme provides bespoke sequence selection for automated workflows in biofoundries. The tool is integrated as part of the pathway design stage into the design-build-test-learn SYNBIOCHEM pipeline. The Selenzyme web server is available athttp://selenzyme.synbiochem.co.uk.
The Microbiomes of Pancreatic Tissue in Pancreatic Cancer and Non-Cancer Subjects
Authors: del Castillo Erika , Meier Richard , Koestler Devin C. , Chen Tsute , Paster Bruce J. , Charpentier Kevin P. , Kelsey Karl T. , Izard Jacques , Michaud Dominique S.
Published: September 2017

Objective

To determine whether bacteria are present in the pancreas of pancreatic cancer and non-cancer subjects and examine whether bacterial profiles vary by site and disease phenotype.

Design

77 patients requiring surgery for pancreatic diseases, or diseases of the foregut, at the Rhode Island Hospital (RIH) were recruited into this study between 2014 and 2016. In addition, 36 whole pancreas were obtained from the National Disease Research Interchange (NDRI) from subjects who were of similar age as the RIH patients and had not died of cancer. The primary exposure of interest was the measurement of the relative abundance of bacterial taxa in all tissue specimens using 16S rRNA gene sequencing.

Results

Number of bacterial reads per sample varied substantially across sample type and patients, but all demonstrated the presence of diverse gastrointestinal bacteria, including bacterial taxa typically identified in the oral cavity. Bacterial profiles were noted to be more similar within individuals across sites in the pancreas, than between individuals by site, suggesting that the pancreas as a whole has its own microbiome. Comparing the mean relative abundance of bacterial taxa in pancreatic cancer patients to those without cancer revealed differences in bacterial taxa previously linked to periodontal disease, includingPorphyromonas.

Conclusions

Bacterial taxa known to inhabit the oral cavity, as well as the intestine, were identified in pancreatic tissue of cancer and non-cancer subjects. Whether any of these bacteria play a causal role in pancreatic carcinogenesis, or are simply opportunistic in nature, needs to be further examined.
On information metrics for spatial coding
Authors: Souza Bryan C. , Pavão Rodrigo , Belchior Hindiael , Tort Adriano B.L.
Published: September 2017

The hippocampal formation is involved in navigation, and its neuronal activity exhibits a variety of spatial correlates (e.g., place cells, grid cells). The quantification of the information encoded by spikes has been standard procedure to identify which cells have spatial correlates. For place cells, most of the established metrics derive from Shannon’s mutual information (Shannon, 1948), and convey information rate in bits/sec or bits/spike (Skaggs et al., 1993; Skaggs et al., 1996). Despite their widespread use, the performance of these metrics in relation to the original mutual information metric has never been investigated. In this work, using simulated and real data, we find that the current information metrics correlate less with the accuracy of spatial decoding than the original mutual information metric. We also find that the top informative cells may differ among metrics, and show a surrogate-based normalization that yields comparable spatial information estimates. Since different information metrics may identify different neuronal populations, we discuss current and alternative definitions of spatially informative cells, which affect the metric choice.
SnapperDB: A database solution for routine sequencing analysis of bacterial isolates
Authors: Dallman Timothy , Ashton Philip , Schafer Ulf , Jironkin Aleksey , Painset Anais , Shaaban Sharif , Hartman Hassan , Myers Richard , Underwood Anthony , Jenkins Claire , Grant Kathie
Published: September 2017

Real-time surveillance of infectious disease using whole genome sequencing data poses challenges in both result generation and communication. SnapperDB represents a set of tools to store bacterial variant data and facilitate reproducible and scalable analysis of bacterial populations. We also introduce the ‘SNP address’ nomenclature to describe the relationship between isolates in a population to the single nucleotide resolution.

We announce the release of SnapperDB v1.0 a program for scalable routine SNP analysis and storage of microbial populations.

Availability

SnapperDB is implemented as a python application under the open source BSD license. All code and user guides are available athttps://github.com/phe-bioinformatics/snapperdb.

Contact

tim.dallman@phe.gov.uk

Supplementary information

Supplementary data are available at Bioinformatics online.
SodaPop: A computational suite for simulating the dynamics of asexual populations
Authors: Gauthier Louis , Di Franco Rémicia , Serohijos Adrian W.R.
Published: September 2017

Motivation

Simulating protein evolution with realistic constraints from population genetics is essential in addressing problems in molecular evolution, from understanding the forces shaping the evolutionary landscape to the clinical challenges of antibiotic resistance, viral evolution and cancer.

Results

To address this need, we present SodaPop, a new forward-time simulator of large asexual populations aimed at studying their structure, dynamics and the distribution of fitness effects with flexible assumptions on the fitness landscape. SodaPop integrates biochemical and biophysical properties in a cell-based, object-oriented framework and provides an efficient, open-source toolkit for performing large-scale simulations of protein evolution.

Availability and implementation

Source code and binaries are freely available athttps://github.com/louisgt/SodaPopunder the GNU GPLv3 license. The software is implemented in C++ and supported on Linux, Mac OS/X and Windows.

Contact

adrian.serohijos@umontreal.ca

Supplementary information

Supplementary information is available on the Github project page.