bluuebunny/crossref_metadata_2025 huggingface dataset:
Low spatial structure and selection against secreted virulence factors attenuates pathogenicity in Pseudomonas aeruginosa
Authors: Granato Elisa T , Ziegenhain Christoph , Marvig Rasmus L , Kümmerli Rolf
Published: July 2018

Bacterial opportunistic pathogens are feared for their difficult-to-treat nosocomial infections and for causing morbidity in immunocompromised patients. Here, we study how such a versatile opportunist, Pseudomonas aeruginosa, adapts to conditions inside and outside its model host Caenorhabditis elegans, and use phenotypic and genotypic screens to identify the mechanistic basis of virulence evolution. We found that virulence significantly dropped in unstructured environments both in the presence and absence of the host, but remained unchanged in spatially structured environments. Reduction of virulence was either driven by a substantial decline in the production of siderophores (in treatments without hosts) or toxins and proteases (in treatments with hosts). Whole-genome sequencing of evolved clones revealed positive selection and parallel evolution across replicates, and showed an accumulation of mutations in regulator genes controlling virulence factor expression. Our study identifies the spatial structure of the non-host environment as a key driver of virulence evolution in an opportunistic pathogen.
Design of tri‐band bandpass filter using symmetrical open stub loaded step impedance resonator
Authors: AbdulRehman M. , Khalid S.
Published: August 2018

A tri‐band bandpass filter design by using conventional stub loaded step impedance resonator (SLSIR) is presented. The proposed SLSIR consists of three tri‐loaded open‐circuited stubs parallel attached to a short and open‐circuited stub. A tri‐band bandpass filter is designed using two proposed symmetrical SLSIR's separated by a short‐circuited stub. In this configuration, the filter produces three bands of frequencies at 0.9, 2.4 and 5.5 GHz, respectively. It is shown that the resonating frequencies can be independently controlled by loaded stubs. For better out of band rejection and increased selectivity, four finite frequency transmission zeros around three passband edges are achieved. The obtained fractional bandwidths are 23, 10 and 17% centred at 0.9, 2.4 and 5.5 GHz, respectively. The proposed design topology is fabricated on a substrate RT/Duroid 5880. The simulated and measured results show good accordance. The fabricated prototype has a compact size of at 0.9 GHz.
Efficient method to identify saddle‐node and limit‐induced bifurcation points of power system
Authors: Jalali Ahvand , Aldeen Mohammad
Published: August 2018

High intermittency in today's renewable‐rich power systems, and the prohibitive cost of upgrading the network infrastructure along with the load growth, has rendered voltage instability an imminent threat for many power systems. This necessitates faster and more efficient ways of identifying the voltage stability (VS) limits, associated with specific bifurcation points of power system model, which are suitable for real‐time applications. To date, continuation power flow (CPF) has conventionally been used to identify bifurcation points of power systems, through plotting power–voltage (P –V) curves. However, existing CPF methods are complex and computationally demanding. To tackle this issue, in this study, accurate identification of both saddle‐node and limit‐induced bifurcation points of power systems is carried out by using a new and efficient continuous power flow algorithm, in which all the complexities associated with the existing CPF methods are relaxed. Low execution time (as compared to the existing CPF methods), ease of implementation, and automated applicability, make the proposed algorithm highly suitable for fast and accurate VS assessment of renewable‐rich, uncertain, power systems. Experiments, carried out on several different size power systems, verify that the proposed method can be effectively used to identify the VS limits of practical real‐life power systems, despite its ease of implementation and lower computational burden.
DAB modulation schema with extended ZVS region for applications with wide input/output voltage
Authors: Garcia‐Bediaga Asier , Villar Irma , Rujas Alejandro , Mir Luis
Published: July 2018

This study is focused on modulation strategies and soft‐switching techniques of the isolated dual‐active‐bridge (DAB) converter for power‐electronics applications, where wide input/output voltage and power ranges are required. The aim of this work is to study the different operation modes and to propose a modulation schema combining five operation modes. The objective of the proposed control strategy is to reduce the switching losses of semiconductors and to improve the overall converter efficiency. Thanks to the use of the single‐active‐bridge modulation, the zero‐voltage‐switching (ZVS) region of the DAB topology is extended, achieving high‐efficiency levels in a wide operation range, even with output voltages close to zero. New analytical expressions are presented in this study to model accurately the behaviour of the DAB converter operation in this extended ZVS region. The influence of non‐dissipative snubbers is also studied including experimental measurements with an insulated gate bipolar transistor‐based 10 kW prototype for the validation of the theoretical study.
Non‐intrusive parameter estimation method for autotuned DC–DC converter based on quasi‐impulse response
Authors: Ali Majid , Loo Ka‐Hong , Lai Yuk‐Ming
Published: July 2018

A non‐intrusive method to estimate the values of power‐stage components online and autotuning of feedback compensator for digitally controlled power converters is presented in this study. By using buck converter as an example, the presented autotuning controller has been designed to cover the wide‐range variations in equivalent series resistance zero of the output capacitor and the resonant frequency of output filter . These two frequencies are estimated by examining the converter's quasi‐impulse response during start‐up and by measuring the output‐voltage ripple during steady‐state operation of the converter. Hence, due to the non‐intrusive characteristic of the proposed control method, the operation of the converter is not affected. Using the acquired results, the online digital compensator is tuned automatically based on predefined crossover frequency and phase margin to provide the required output‐voltage regulation and transient response under wide‐range variations in the power‐stage component values. To validate the effectiveness of the proposed control method, experimental results from a 12 to 1.5 V buck converter are presented.
Improving the efficiency of the production process using SMED
Authors: Skotnicka-Zasadzień Bożena , Wolniak Radosław , Gębalska-Kwiecień Anna
Published: July 2018

The article presents one of the methods of management used in quality engineering, i.e. the SMED, which is applied to streamline the functioning of machines used on a production line. The research problem that was analysed on one of the production lines was too long a retooling time which resulted in too high a cost of the operation which, consequently, resulted in excessive overall production costs. The main aim of the actions undertaken when applying the SMED method was to identify potentially problematic areas and reduce the retooling time. All those actions allowed to minimise production costs, and improved the functioning of the company as well as the efficiency of the production process.
Identifying key criteria in development of Industrial Engineering education
Authors: Nitkiewicz Tomasz , Ayen Zuhal
Published: July 2018

The objective of this study is to define criteria in current development of Industrial Engineering (IE) education on the basis of studies and concepts published in commonly accessible databases and knowledge exchange platforms. General assumption of the study is that the universal criteria used in developing IE study programs are already defined and some experiences on their use are already published. The expected outcome of the study is to identify the criteria that could support the development of curriculum for MSc in IE. The approach used here is content analysis with the publication related to the higher level education in the field of Industrial Engineering.
A multi-criteria decision making approach in lighting technology selection for a production hall
Authors: Cristea Maria , Adrian Tîrnovan Radu , Cristea Ciprian , Sorin Pică Constantin
Published: July 2018

Nowadays, lighting industry can contribute to a more sustainable future, by reducing the total consumption of electrical energy used to illuminate indoor and outdoor spaces. Thus, lighting system design is one of the important components when thinking about building sustainability. Taking into account the final purpose of the lighting installation (the type of human activity that will take place in the indoor space for which lighting is to be provided), the most suitable lighting technologies are selected considering their characteristics, dimensions, and technical specification. The paper presents how a lighting technology selection for a production hall using a multi-criteria decision making approach. There are considered the most common luminaires and lamps which can assure the illuminance necessary for the hall, which represent the variants, evaluated against several criteria, considering the decision maker’s preferences and constraints. The variants are ranked according to their performance for each criterion. The optimal lighting solution obtained after the simulation experiment suggests that ELECTRE III method is a practical decision-making model that can be considered for this type of decisions.
Absorption of management knowledge in Romanian small and medium-sized enterprises
Authors: Moraru Gina-Maria , Popa Daniela
Published: July 2018

One aim of this paper is to prove that the absorption of management knowledge in Romanian small and medium-sized enterprises (SMEs) has many gaps. Another aim is to find the main causes of this. Paper begins with a short bibliographical study about the most important weakness of the Romanian SMEs: the low availability of skilled staff or experienced managers. In order to discover which phase of knowledge management in these firms is the most problematic, we have made an exploratory research based on the use of Fishbein-Rosenberg model for measuring managers' opinions on this subject. The results have proved that the management knowledge absorption is done to a small extent in Romanian SMEs. In order to find the main causes of the poor management knowledge absorption, we have next developed a research based on questionnaires. We have discovered that the studied problem has its roots both in the business environment and in the academic environment.
Study on improving silicone losses in the process of mixing components of soldering machines
Authors: Victor Zerbes Mihai , Georgeta Popescu Liliana
Published: July 2018

The paper presents a summary of the steps of the 6 Sigma methodology applied in the gluing section within an automotive company form Sibiu, Romania. We describe the synthesis of each step of the DMAIC model, a well-known model in the application of the 6 Sigma methodology. In the last chapter, we outline some general conclusions regarding the use of the 6 Sigma methodology presenting the benefits both within the automotive organization from Sibiu and its general use by industrial organizations.
A tuned vibration absorber constituted of shape memory alloy wires for vibration reduction of platform structures: design and implementation
Authors: Liao Yun-Ting , Lin Jia-Hong , Lee Chun-Ying
Published: July 2018

Machinery can suffer from mechanical vibrations since resonance may be generated from time-varying external excitations under different operation conditions. These detrimental vibrations may significantly influence the device's performance, effectiveness and reliability in operation. In this paper, an innovative, simple and high-efficiency tuned vibration absorber (TVA) consisting of shape memory alloy (SMA) wires, which is referred to a wire-type tuned vibration absorber (WTVA), is proposed to reduce the induced vibration. Experiments are carried out using a six-degree-of-freedom platform which is designed to simulate the frame of precision machinery in practical applications. With the equivalent stiffness of SMA wires adjusted by the controlled electric current, the frequency tunability of WTVA can be achieved. When the natural frequency of WTVA tuned in with the disturbance frequency, the experimental results demonstrate that the efficiency in vibration reduction of the platform is drastically increased even with considerable weight difference between WTVA and the platform. Moreover, the tunable frequency span also increases greatly due to the new design of WTVA and the material characteristics of SMA wires.
Zur Anwendung der Ballon-Kyphoplastie/Vertebroplastie
Authors: Amling M. , Baier M. , Blattert T. , Euler E. , Götte S. , Kaps P. , Kasperk H. , Kurth A. , Meeder P.-J. , Schwarz H. , Steinleitner W. E. , Weißkopf M. , Haas H. ,   Vorsitzender der Autorengruppe
Published: August 2018

In der Behandlung osteoporotischer Wirbelkörperfrakturen finden die minimalinvasiven Methoden der Ballon-Kyphoplastie und der Vertebroplastie zunehmende Verbreitung. In der aktuellen Leitlinie zur Behandlung der Osteoporose ist aufgrund der eingeschränkten Studienlage eine sehr konservative Aussage zur Anwendung der Verfahren getroffen worden. Die vorliegende Arbeit stellt eine Bewertung beider Verfahren hinsichtlich Indikation, technischer Durchführung und notwendiger Voraussetzungen dar. Sie wurde erstellt durch eine vom DVO beauftragte Arbeitsgruppe und soll bestehende Unsicherheiten im Zusammenhang mit beiden Verfahren reduzieren.
Knochenmetastasen
Authors: Ebert R. , Rauner M. , Rachner T. , Schütze N. , Glüer C.-C. , Hofbauer L. C. , Jakob F. ,   für das SkelMet Konsortium
Published: August 2018

Knochenmetastasen sind ein klinisch relevantes Problem und ihre Inzidenz nimmt zu. Die Fähigkeit von Tumorzellen, in den Knochen zu metastasieren, erfordert zellbiologische Veränderungen, die zur Migration und zur aktiven Überwindung von Barrieren wie Basalmembranen und Extrazellulärmatrix befähigen. Das „Homing” im Knochen findet dann statt, wenn Tumorzellen dort anheften und gut überleben können. Die Interaktion der beteiligten Zelltypen bewirkt eine Änderung des Phänotyps in allen Partnern einer solchen „malignen Konversation”. Die resultierende Signatur ist oft permanent und führt auf der einen Seite zu einer Suszeptibilität des Stromas für die Metastasierung und auf der anderen Seite zu einer starken Veränderung der Tumorbiologie, die sich vom Primärtumor wesentlich unterscheidet. In einem klassischen Circulus vitiosus können Tumorzellen direkt und indirekt Osteoklasten stimulieren und Osteolysen verursachen. Auf die Osteoblastenfunktion können sie zweierlei Auswirkungen haben. Sie können die Mineralisierung stark stimulieren und damit osteoblastische Metastasen verursachen, sie können aber auch starke Hemmstoffe der Knochenregeneration ausschütten, die eine Osteoplegie hervorrufen, ein völliges Lahm legen der Knochenregeneration. Die Kombination aus Osteolyse und Osteoplegie führt klinisch zu einer besonders schwerwiegenden Situation des Knochenverlusts mit pathologischen Frakturen. Die geschützten Stammzellnischen des Knochenmarks sind auch für Tumorzellen eine gute Möglichkeit zum Überleben. Tumorzellen können sich diese Nischen selbst induzieren. Sie können sich dabei in Richtung Tumorstammzelle verändern und können später zum Ausgangspunkt von Tumorrezidiven werden. Es ist daher für die Zukunft sinnvoll, den Knochen und das Knochenmark als therapeutische Zielstrukturen in onkologische Therapiekonzepte einzubeziehen.
Flexible Analogues of Azaindole DYRK1A Inhibitors Elicit Cytotoxicity in Glioblastoma Cells
Authors: Zhou Qingqing , Reekie Tristan A. , Abbassi Ramzi H. , Venkata Dinesh Indurthi , Font Josep S. , Ryan Renae M. , Rendina Louis M. , Munoz Lenka , Kassiou Michael
Published: July 2018

DYRK1A is a novel target for epidermal growth factor receptor (EGFR)-dependent glioblastoma and it represents a promising strategy for cancer therapy. DYRK1A inhibition has been found to promote EGFR degradation in glioblastoma cells by triggering endocytosis and lysosomal degradation, thus reducing the self-renewal ability of tumorigenic cells. Using a deconstruction approach of a DYRK1A lead molecule DANDY (1a), a set of novel ring-opened compounds was prepared. Despite showing no activity towards DYRK1A, a reduction in the viability of glioblastoma cells was observed with some of the compounds. This suggests other mechanistic pathways are leading to the apoptosis of glioblastoma cells.
Correlation-based feature optimization and object-based approach for distinguishing shallow and deep-seated landslides using high resolution airborne laser scanning data
Authors: Rmezaal M , Pradhan B
Published: July 2018

Landslides post great threats to many regions globally, particularly in densely vegetated areas where they are hard to identify. Thus, in order to address this issue, precise inventory mapping methods are required in order to gauge landslide susceptibility in regions, as well as hazards and risk. Obstacles in the development of such mapping methods, however, are optimization techniques to employ, feature selection methods, as well as the development of model transferability. The present study seeks to utilize correlation-based feature selection and object-based approach in conjunction with LiDAR data, whereby LiDAR-DEM derived digital elevation alongside high-resolution orthophotos are employed in tandem. Next, fuzzy-based segmentation parameter optimizer was employed in order to optimize segmentation parameters. Next, support vector machine was employed in order to assess the effectiveness of the proposed method, with results illustrating the algorithm’s robustness with regards to landslide identification. The results of transferability also demonstrated the ease of use for the method, as well as its accuracy and capability to identify landslides as either shallow or deep-seated. To summarize, the study proposes that the developed methods are greatly effective in landslide detection, especially in tropical regions such as in Malaysia.
When is an automatic set an additive basis?
Authors: Bell Jason , Hare Kathryn , Shallit Jeffrey
Published: August 2018

We characterize those

k
k

-automatic sets

S
S

of natural numbers that form an additive basis for the natural numbers, and we show that this characterization is effective. In addition, we give an algorithm to determine the smallest

j
j

such that

S
S

forms an additive basis of order

j
j

, if it exists.
Design of accurate formulas for approximating functions in weighted Hardy spaces by discrete energy minimization
Authors: Tanaka Ken’ichiro , Sugihara Masaaki
Published: July 2018

We propose a simple and effective method for designing approximation formulas for weighted analytic functions. We consider spaces of such functions according to weight functions expressing the decay properties of the functions. Then we adopt the minimum worst error of the $n$-point approximation formulas in each space for characterizing the optimal sampling points for the approximation. In order to obtain approximately optimal sampling points we consider minimization of a discrete energy related to the minimum worst error. Consequently, we obtain an approximation formula and its theoretical error estimate in each space. In addition, from some numerical experiments, we observe that the formula generated by the proposed method outperforms the corresponding formula derived with sinc approximation, which is near optimal in each space.
Convergent numerical method for the Navier–Stokes–Fourier system: a stabilized scheme
Authors: Hošek Radim , She Bangwei
Published: July 2018

We propose a combined finite volume--finite element method for the compressible Navier–Stokes–Fourier system. A finite volume approximation is used for the density and energy equations while a finite element discretization based on the nonconforming Crouzeix–Raviart element is applied to the momentum equation. We show the stability, the consistency and finally the convergence of the scheme (up to a subsequence) toward a suitable weak solution. We are interested in the diffusive term in the form of divergence of the symmetric velocity gradient instead of the classical Laplace form appearing in the momentum equation. As a consequence, there emerges the need to add a stabilization term that substitutes the role of Korn’s inequality which does not hold in the Crouzeix–Raviart element space. The present work is a continuation of Feireisl, E., Hošek, R. & Michálek, M. (2016, A convergent numerical method for the Navier–Stokes–Fourier system. IMA J. Numer. Anal., 36, 1477--1535), where a similar scheme is studied for the case of classical Laplace diffusion. We compare the two schemes and point out that the discretization of the energy diffusion terms in the reference scheme is not compatible with the model. Finally, we provide several numerical experiments for both schemes to demonstrate the numerical convergence, positivity of the discrete density, as well as the difference between the schemes.
Strong $L^2$ convergence of time numerical schemes for the stochastic two-dimensional Navier–Stokes equations
Authors: Bessaih Hakima , Millet Annie
Published: July 2018

We prove that some time discretization schemes for the two-dimensional Navier–Stokes equations on the torus subject to a random perturbation converge in $L^2(\varOmega )$. This refines previous results that established the convergence only in probability of these numerical approximations. Using exponential moment estimates of the solution of the stochastic Navier–Stokes equations and convergence of a localized scheme we can prove strong convergence of fully implicit and semiimplicit temporal Euler discretizations and of a splitting scheme. The speed of the $L^2(\varOmega )$ convergence depends on the diffusion coefficient and on the viscosity parameter.
Smooth Equivalence of Deformations of Domains in Complex Euclidean Spaces
Authors: Gaussier Hervé , Gong Xianghong
Published: July 2018

We prove that two smooth families of 2-connected domains in $\mathbf{C}$ are smoothly equivalent if they are equivalent under a possibly discontinuous family of biholomorphisms. We construct, for $\infty > m \geq 3$, two smooth families of smoothly bounded $m$-connected domains in $\mathbf{C}$, and for $n\geq 2$, two families of strictly pseudoconvex domains in $\mathbf{C}^n$, which are equivalent under discontinuous families of biholomorphisms but not under any continuous family of biholomorphisms. Finally, we give sufficient conditions for the smooth equivalence of two smooth families of domains.
Anticoagulant medication errors in hospitals and primary care: a cross-sectional study
Authors: Dreijer Albert R , Diepstraten Jeroen , Bukkems Vera E , Mol Peter G M , Leebeek Frank W G , Kruip Marieke J H A , van den Bemt Patricia M L A
Published: July 2018

Objective

To assess the proportion of all medication error reports in hospitals and primary care that involved an anticoagulant. Secondary objectives were the anticoagulant involved, phase of the medication process in which the error occurred, causes and consequences of 1000 anticoagulant medication errors. Additional secondary objectives were the total number of anticoagulant medication error reports per month, divided by the total number of medication error reports per month and the proportion of causes of 1000 anticoagulant medication errors (comparing the pre- and post-guideline phase).

Design

A cross-sectional study.

Setting

Medication errors reported to the Central Medication incidents Registration reporting system.

Participants

Between December 2012 and May 2015, 42 962 medication errors were reported to the CMR.

Intervention

N/A.

Main outcome measure

Proportion of all medication error reports that involved an anticoagulant. Phase of the medication process in which the error occurred, causes and consequences of 1000 anticoagulant medication errors. The total number of anticoagulant medication error reports per month, divided by the total number of medication error reports per month (comparing the pre- and post-guideline phase) and the total number of causes of 1000 anticoagulant medication errors before and after introduction of the LSKA 2.0 guideline.

Results

Anticoagulants were involved in 8.3% of the medication error reports. A random selection of 1000 anticoagulant medication error reports revealed that low-molecular weight heparins were most often involved in the error reports (56.2%). Most reports concerned the prescribing phase of the medication process (37.1%) and human factors were the leading cause of medication errors mentioned in the reports (53.4%). Publication of the national guideline on integrated antithrombotic care had no effect on the proportion of anticoagulant medication error reports. Human factors were the leading cause of medication errors before and after publication of the guideline.

Conclusions

Anticoagulant medication errors occurred in 8.3% of all medication errors. Most error reports concerned the prescribing phase of the medication process. Leading cause was human factors. The publication of the guideline had no effect on the proportion of anticoagulant medication errors.
Management of Insecticide-Resistant Soybean Aphids in the Upper Midwest of the United States
Authors: Koch Robert L , Hodgson Erin W , Knodel Janet J , Varenhorst Adam J , Potter Bruce D
Published: July 2018

Since the first observation of soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), in North America in 2000, it has become the most economically damaging insect of soybean in the Upper Midwest of the United States. For the last 17 yr, soybean aphid management has relied almost entirely on the use of foliar-applied broad-spectrum insecticides. However, in 2015 in Minnesota, failures of foliar-applied pyrethroid insecticides were reported and pyrethroid resistance was confirmed with laboratory bioassays using lambda-cyhalothrin and bifenthrin. In 2016 and 2017, further reports of failures of pyrethroid insecticides and/or laboratory confirmation of resistance occurred in Iowa, North Dakota, South Dakota, and Manitoba. In response to the challenge posed by insecticide-resistant soybean aphids, we recommend several management strategies for minimizing further development of resistance and subsequent pest-induced crop losses: 1) scout and use the economic threshold to determine when to apply insecticides, 2) apply the insecticides properly, 3) assess efficacy 3–5 d after application, and 4) alternate to a different insecticide group if another application is required. In the long term, soybean aphid management must move beyond insecticide-based management to true integrated pest management by incorporating multiple tactics.
Gender Matters in Economic Empowerment Interventions: A Research Review
Authors: Buvinić Mayra , O'Donnell Megan
Published: July 2018

Evidence shows that women face additional constraints because of their gender that affect their economic performance. A review of recent evaluation research demonstrates the types of gender-related constraints women face and the role that economic empowerment interventions can play in overcoming them, especially if they incorporate aspects of smart design, increasing their development impact. The evidence suggests that financial services and training programs are not gender-neutral and that specific design features can yield more positive economic outcomes for women by helping them overcome gender-related constraints. These features include savings and “Graduation” programs that increase women's economic independence, self-reliance and self-control, and the practice of repeated micro-borrowing that increases financial risk-taking and choice. “Smart” design also includes high-quality business management and jobs skills training, and stipends and other incentives in these training programs that address women's and young women's additional time burdens and childcare demands. Peer support may also help to increase financial risk-taking and confidence in business decisions. However, when social norms are too restrictive, and women are prevented from doing any paid work, no design will be smart enough. Subjective economic empowerment appears to be an important intermediate outcome for women that should be promoted and more reliably and accurately measured. Lastly, whenever possible, results should be sex-disaggregated and reported for individuals as well as households.
The Nucleome of Developing Murine Rod Photoreceptors
Authors: Diri Issam Al , Valentine Marc , Xu Beisi , Putnam Daniel , Griffiths Lyra , Lupo Marybeth , Norrie Jackie , Zhang Jiakun , Johnson Dianna , Easton John , Shao Ying , Honnell Victoria , Frase Sharon , Miller Shondra , Stewart Valerie , Chen Xiang , Dyer Michael A.
Published: July 2018

The nuclei of rod photoreceptors in mice and other nocturnal species have an unusual inverted chromatin structure: the heterochromatin is centrally located to help focus light and improve photosensitivity. To better understand this unique nuclear organization, we performed ultra-deep Hi-C analysis on murine retina at 3 stages of development and on purified rod photoreceptors. Predicted looping interactions from the Hi-C data were validated with fluorescence in situ hybridization (FISH). We discovered that a subset of retinal genes that are important for retinal development, cancer, and stress response are localized to the facultative heterochromatin domain. We also used machine learning to develop an algorithm based on our chromatin Hidden Markov Modeling (chromHMM) of retinal development to predict heterochromatin domains and study their dynamics during retinogenesis. FISH data for 264 genomic loci were used to train and validate the algorithm. The integrated data were then used to identify a developmental stage– and cell type-specific core regulatory circuit super-enhancer (CRC-SE) upstream of the Vsx2 gene, which is required for bipolar neuron expression. Deletion of the Vsx2 CRC-SE in mice led to the loss of bipolar neurons in the retina.
Walking along chromosomes with super-resolution imaging, contact maps, and integrative modeling
Authors: Nir Guy , Farabella Irene , Estrada Cynthia Pérez , Ebeling Carl G. , Beliveau Brian J. , Sasaki Hiroshi M. , Lee Soun H. , Nguyen Son C. , McCole Ruth B. , Chattoraj Shyamtanu , Erceg Jelena , Abed Jumana AlHaj , Martins Nuno M. C. , Nguyen Huy Q. , Hannan Mohammed A. , Russell Sheikh , Durand Neva C. , Rao Suhas S.P. , Kishi Jocelyn Y. , Soler-Vila Paula , Di Pierro Michele , Onuchic José N. , Callahan Steven , Schreiner John , Stuckey Jeff , Yin Peng , Aiden Erez Lieberman , Marti-Renom Marc A. , Wu C.-ting
Published: July 2018

Chromosome structure is thought to be crucial for proper functioning of the nucleus. Here, we present a method for visualizing chromosomal DNA at super-resolution and then integrating Hi-C data to produce three-dimensional models of chromosome organization. We begin by applying Oligopaint probes and the single-molecule localization microscopy methods of OligoSTORM and OligoDNA-PAINT to image 8 megabases of human chromosome 19, discovering that chromosomal regions contributing to compartments can form distinct structures. Intriguingly, our data also suggest that homologous maternal and paternal regions may be differentially organized. Finally, we integrate imaging data with Hi-C and restraint-based modeling using a method calledintegrativemodeling ofgenomicregions (IMGR) to increase the genomic resolution of our traces to 10 kb.

One Sentence Summary

Super-resolution genome tracing, contact maps, and integrative modeling enable 10 kb resolution glimpses of chromosome folding.
The molecular signatures of compatible and incompatible pollination
Authors: Kodera Chie , Just Jérémy , Da Rocha Martine , Larrieu Antoine , Riglet Lucie , Legrand Jonathan , Rozier Frédérique , Gaude Thierry , Fobis-Loisy Isabelle
Published: July 2018

Fertilization in flowering plants depends on the early contact and recognition of pollen grains by the receptive papilla cells of the stigma. To identify the associated molecular pathways, we developed a transcriptomic analysis based on single nucleotide polymorphisms (SNPs) present in twoArabidopsis thalianaaccessions, one used as female and the other as male. We succeeded in distinguishing 80 % of transcripts according to their parental origins and drew up a catalog of genes whose expression is modified after pollen-stigma interaction. Global analysis of our data reveals that pattern-triggered immunity (PTI)-associated transcripts are upregulated after compatible pollination. From our analysis, we predicted the activation of the Mitogen-activated Protein Kinase 3 on the female side after compatible pollination, which we confirmed through expression and mutant analysis. Our work defines the molecular signatures of compatible and incompatible pollination, highlights the active status of incompatible stigmas, and unravels a new MPK3-dependent cell wall feature associated with stigma-pollen interaction.
Monkey Features Location Identification Using Convolutional Neural Networks
Authors: Labuguen (P) Rollyn , Gaurav Vishal , Blanco Salvador Negrete , Matsumoto Jumpei , Inoue Kenichi , Shibata Tomohiro
Published: July 2018

Understanding animal behavior in its natural habitat is a challenging task. One of the primary step for analyzing animal behavior is feature detection. In this study, we propose the use of deep convolutional neural network (CNN) to locate monkey features from raw RGB images of monkey in its natural environment. We train the model to identify features such as the nose and shoulders of the monkey at about 0.01 model loss.
Quantitative comparison of the anterior-posterior patterning system in the embryos of fiveDrosophilaspecies
Authors: Wunderlich Zeba , Fowlkes Charless C. , Eckenrode Kelly B. , Bragdon Meghan D. J. , Abiri Arash , DePace Angela H.
Published: July 2018

Complex spatiotemporal gene expression patterns direct the development of the fertilized egg into an adult animal. Comparisons across species show that, in spite of changes in the underlying regulatory DNA sequence, developmental programs can be maintained across millions of years of evolution. Reciprocally, changes in gene expression can be used to generate morphological novelty. Distinguishing between changes in regulatory DNA that lead to changes in gene expression and those that do not is therefore a central goal of evolutionary developmental biology. Quantitative, spatially-resolved measurements of developmental gene expression patterns play a crucial role in this goal, enabling the detection of subtle phenotypic differences between species and the development of computations models that link the sequence of regulatory DNA to expression patterns. Here we report the generation of two atlases of cellular resolution gene expression measurements for the primary anterior-posterior patterning genes inDrosophila simulansandDrosophila virilis. By combining these data sets with existing atlases for three otherDrosophilaspecies, we detect subtle differences in the gene expression patterns and dynamics driving the highly conserved axis patterning system and delineate inter-species differences in the embryonic morphology. These data sets will be a resource for future modeling studies of the evolution of developmental gene regulatory networks.
MOVIE: Multi-Omics Visualization of Estimated contributions
Authors: McCabe Sean D. , Lin Dan-Yu , Love Michael I.
Published: July 2018

The growth of multi-omics datasets has given rise to many methods for identifying sources of common variation across data types. The unsupervised nature of these methods makes it difficult to evaluate their performance. We present MOVIE, Multi-Omics Visualization of Estimated contributions, as a framework for evaluating the degree of overfitting and the stability of unsupervised multi-omics methods. MOVIE plots the contributions of one data type against another to produce contribution plots, where contributions are calculated for each subject and each data type from the results of each multi-omics method. The usefulness of MOVIE is demonstrated by applying existing multi-omics methods to permuted null data and breast cancer data from The Cancer Genome Atlas. Contribution plots indicated that principal components-based Canonical Correlation Analysis overfit null data, while Sparse multiple Canonical Correlation Analysis and Multi-Omics Factor Analysis provided stable results with high specificity for both the real and permuted null datasets.

Availability

MOVIE is available as an R package at https://github.com/mccabes292/movie

Contact

milove@email.unc.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
Migration rather than proliferation transcriptomic signatures are strongly associated with breast cancer patient survival
Authors: Nair Nishanth Ulhas , Das Avinash , Rogkoti Vasiliki-Maria , Fokkelman Michiel , Marcotte Richard , de Jong Chiaro G. , Lee Joo Sang , Meilijson Isaac , Hannenhalli Sridhar , Neel Benjamin G. , van de Water Bob , Le Dévédec Sylvia E. , Ruppin Eytan
Published: July 2018

The efficacy of prospective cancer treatments is routinely estimated by in vitro cell-line proliferation screens. However, it is unclear whether tumor aggressiveness and patient survival are influenced more by the proliferative or the migratory properties of cancer cells. To address this question, we experimentally measured proliferation and migration phenotypes across more than 40 breast cancer cell-lines. Based on the latter, we built and validated individual predictors of breast cancer proliferation and migration levels from the cells’ transcriptomics. We then apply these predictors to estimate the proliferation and migration levels of more than 1000 TCGA breast cancer tumors. Reassuringly, both estimates increase with tumor’s aggressiveness, as qualified by its stage, grade, and subtype. However, predicted tumor migration levels are significantly more strongly associated with patient survival than the proliferation levels. We confirm these finding by conducting siRNA knock-down experiments on the highly migratory MDA-MB-231 cell lines and deriving gene knock-down based proliferation and migration signatures. We show that cytoskeletal drugs might be more beneficial in patients with high predicted migration levels. Taken together, these results testify to the importance of migration levels in determining patient survival.
Dietary long-chain omega-3 fatty acids are related to impulse control and anterior cingulate function in adolescents
Authors: Darcey Valerie L. , McQuaid Goldie A. , Fishbein Diana H. , VanMeter John W.
Published: July 2018

Impulse control, an emergent function modulated by the prefrontal cortex (PFC), helps to dampen risky behaviors during adolescence. Influences on PFC maturation during this period may contribute to variations in impulse control. Availability of omega-3 fatty acids, an essential dietary nutrient integral to neuronal structure and function, may be one such influence. This study examined whether intake of energy-adjusted long-chain omega-3 fatty acids (eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)) was related to variation in impulse control and PFC activity during performance of an inhibitory task in adolescents (n= 87; 51.7% female, mean age 13.3+1.1 years) enrolled in a longitudinal neuroimaging study. Intake of DHA+EPA was assessed using a food frequency questionnaire and adjusted for total energy intake. Inhibitory control was assessed using caregiver rating scale (BRIEF Inhibit subscale) and task performance (false alarm rate) on a Go/No-Go task performed during functional MRI. Reported intake of long-chain omega-3 was positively associated with caregiver ratings of adolescent ability to control impulses (p=0.017) and there was a trend for an association between intake and task-based impulse control (p=0.072). Furthermore, a regression of BOLD response within PFC during successful impulse control (Correct No-Go versus Incorrect NoGo) with energy-adjusted DHA+EPA intake revealed that adolescents reporting lower intakes display greater activation in the dorsal anterior cingulate, potentially suggestive of a possible lag in cortical development. The present results suggest that dietary omega-3 fatty acids are related to development of both impulse control and function of the dorsal anterior cingulate gyrus in normative adolescent development. Insufficiency of dietary omega-3 fatty acids during this developmental period may be a factor which hinders development of behavioral control.
Plasticity in Escherichia coli cell wall metabolism promotes fitness and mediates intrinsic antibiotic resistance across environmental conditions
Authors: Mueller Elizabeth A , Levin Petra Anne
Published: July 2018

Although the peptidoglycan cell wall is an essential structural and morphological feature of most bacterial cells, the extracytoplasmic enzymes involved in its synthesis are frequently dispensable under standard culture conditions. By modulating a single growth parameter—extracellular pH—we discovered a subset of these so-called “redundant” enzymes in Escherichia coli are required for maximal fitness across pH environments. Among these pH specialists are the class A penicillin binding proteins PBP1 a and PBP1 b; defects in these enzymes attenuate growth in alkaline and acidic conditions, respectively. Genetic, biochemical, and cytological studies demonstrate that synthase activity is required for cell wall integrity across a wide pH range, and differential activity across pH environments significantly alters intrinsic resistance to cell wall active antibiotics. Together, our findings reveal previously thought to be redundant enzymes are instead specialized for distinct environmental niches, thereby ensuring robust growth and cell wall integrity in a wide range of conditions.
Analysis of the impact of molecular motions on the efficiency of XL-MS and the distance restraints in hybrid structural biology
Authors: Svetlov Vladimir , Nudler Evgeny
Published: July 2018

Covalent cross-link mapping by mass spectrometry (XL-MS) is rapidly becoming the most widely used method of hybrid structural biology. We investigated the impact of incremental variations of cross-linker length have on the depth of XL-MS interrogation of protein-protein complexes, and assessed the role molecular motions in solution play in generation of cross-link-derived distance restraints. Supplementation of a popular NHS-ester cross-linker, DSS, with 2 reagents shorter or longer by CH2-CH2, increased the number of non-reductant cross-links by ~50%. Molecular dynamics simulations of these cross-linkers revealed 3 individual, partially overlapping ranges of motion, consistent with partially overlapping sets of cross-links formed by each reagent. Similar simulations elucidated protein fold-specific ranges of motions for the reactive and backbone atoms from rigid and flexible target domains. Together these findings create a quantitative framework for generation of cross-linker- and protein fold-specific distance restraints for XL-MS-guided protein-protein docking.
Gene cluster conservation identifies melanin and perylenequinone biosynthesis pathways in multiple plant pathogenic fungi
Authors: Ebert Malaika K. , Spanner Rebecca E. , Jonge Ronnie de , Smith David J. , Holthusen Jason , Secor Gary A. , Thomma Bart P.H.J. , Bolton Melvin D.
Published: July 2018

Perylenequinones are a family of structurally related polyketide fungal toxins with nearly universal toxicity. These photosensitizing compounds absorb light energy which enables them to generate reactive oxygen species that damage host cells. This potent mechanism serves as an effective weapon for plant pathogens in disease establishment. The sugar beet pathogenCercospora beticolasecretes the perylenequinone cercosporin during infection. We have shown recently that the cercosporin toxin biosynthesis(CTB)gene cluster is present in several other phytopathogenic fungi, prompting the search for biosynthetic gene clusters (BGCs) of structurally similar perylenequinones in other fungi. Here, we report the identification of the elsinochrome and phleichrome BGCs ofElsinoё fawcettiiandCladosporium phlei,respectively, based on gene cluster conservation with theCTBand hypocrellin BGCs. Furthermore, we show that previously reported BGCs for elsinochrome and phleichrome are involved in melanin production. Phylogenetic analysis of the corresponding melanin polyketide synthases (PKSs) and alignment of melanin BGCs revealed high conservation between the established and newly identifiedC. beticola, E. fawcettii,andC. phleimelanin BGCs. Mutagenesis of the identified perylenequinone and melanin PKSs inC. beticolaandE. fawcettiicoupled with mass spectrometric metabolite analyses confirmed their roles in toxin and melanin production.

Originality and significance statement

Genes involved in secondary metabolite (SM) production are often clustered together to form biosynthetic pathways. These pathways frequently have highly conserved keystone enzymes which can complicate allocation of a biosynthetic gene cluster (BGC) to the cognate SM. In our study, we utilized a combination of comparative genomics, phylogenetic analyses and biochemical approaches to reliably identify BGCs for perylenequinone toxins and DHN-melanin in multiple plant pathogenic fungi. Furthermore, we show that earlier studies that aimed to identify these perylenequinone pathways were misdirected and actually reported DHN-melanin biosynthetic pathways. Our study outlines a reliable approach to successfully identify fungal SM pathways.