bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracting the potential-well of a near-field optical trap using the Helmholtz-Hodge decomposition
Authors: Zaman Mohammad Asif , Padhy Punnag , Hansen Paul C. , Hesselink Lambertus
Published: March 2018

The non-conservative nature of the force field generated by a near-field optical trap is analyzed. A plasmonic C-shaped engraving on a gold film is considered as the trap. The force field is calculated using the Maxwell stress tensor method. The Helmholtz-Hodge decomposition is used to extract the conservative and the non-conservative component of the force. Due to the non-negligible non-conservative component, it is found that the conventional approach of extracting the potential by direct integration of the force is not accurate. Despite the non-conservative nature of the force field, it is found that the statistical properties of a trapped nanoparticle can be estimated from the conservative component of the force field alone. Experimental and numerical results are presented to support the claims.
Simulation of multi-pulse coaxial helicity injection in the Sustained Spheromak Physics Experiment
Authors: O'Bryan J. B. , Romero-Talamás C. A. , Woodruff S.
Published: March 2018

Nonlinear, numerical computation with the NIMROD code is used to explore magnetic self-organization during multi-pulse coaxial helicity injection in the Sustained Spheromak Physics eXperiment. We describe multiple distinct phases of spheromak evolution, starting from vacuum magnetic fields and the formation of the initial magnetic flux bubble through multiple refluxing pulses and the eventual onset of the column mode instability. Experimental and computational magnetic diagnostics agree on the onset of the column mode instability, which first occurs during the second refluxing pulse of the simulated discharge. Our computations also reproduce the injector voltage traces, despite only specifying the injector current and not explicitly modeling the external capacitor bank circuit. The computations demonstrate that global magnetic evolution is fairly robust to different transport models and, therefore, that a single fluid-temperature model is sufficient for a broader, qualitative assessment of spheromak performance. Although discharges with similar traces of normalized injector current produce similar global spheromak evolution, details of the current distribution during the column mode instability impact the relative degree of poloidal flux amplification and magnetic helicity content.
Isotope effect on the quantum thermal transport of carbyne
Authors: Wu Yu , Zhao Jing , Sun Guangyu , Shi Lei
Published: March 2018

The isotope effect on the quantum thermal transport of carbyne is studied by combining the central insertion scheme and the non-equilibrium Green's function method based on density function theory. This combined method avoids the disadvantage of the cascading scattering model and scaling theory method, which in principle only can process the phonon with low-concentration (≤10%) isotope impurity scattering. Also, the molecular dynamics method greatly overestimates the carbyne thermal transport property. By using our combined method, the calculated thermal conductivity of 100% 12C carbyne with the phonon mean free path of 775 nm at room temperature is 4.44 × 103 W m−1 K−1. When a 12C carbyne consisting of 400 carbon atoms is randomly mixed with 13C or 14C atoms at 300 K, the largest isotope effect of thermal conductance locates at the mixing ratio of 50% 13C/14C. Compared to the pure 12C carbyne, the average thermal conductance is reduced by 30% and 49% for the 13C and 14C, respectively.
Communication: Introducing prescribed biases in out-of-equilibrium Markov models
Authors: Dixit Purushottam D.
Published: March 2018

Markov models are often used in modeling complex out-of-equilibrium chemical and biochemical systems. However, many times their predictions do not agree with experiments. We need a systematic framework to update existing Markov models to make them consistent with constraints that are derived from experiments. Here, we present a framework based on the principle of maximum relative path entropy (minimum Kullback-Leibler divergence) to update Markov models using stationary state and dynamical trajectory-based constraints. We illustrate the framework using a biochemical model network of growth factor-based signaling. We also show how to find the closest detailed balanced Markov model to a given Markov model. Further applications and generalizations are discussed.
Locating lightning
Authors: Murphy Martin
Published: March 2018

Air traffic controllers guiding planes, insurance adjusters validating claims, meteorologists forecasting weather, and more want to know where lightning strikes. Modern location systems provide them with the information they need.
Women show similar central and peripheral fatigue to men after half‐marathon*
Authors: Boccia Gennaro , Dardanello Davide , Tarperi Cantor , Festa Luca , La Torre Antonio , Pellegrini Barbara , Schena Federico , Rainoldi Alberto
Published: March 2018

Women are known to be less fatigable than men in single‐joint exercises, but fatigue induced by running has not been well understood. Here we investigated sex differences in central and peripheral fatigue and in rate of force development (RFD) in the knee extensors after a half‐marathon run. Ten male and eight female amateur runners (aged 25–50 years) were evaluated before and immediately after a half‐marathon race. Knee extensors forces were obtained under voluntary and electrically evoked isometric contractions. Maximal voluntary isometric contraction (MVC) force and peak RFD were recorded. Electrically doublet stimuli were delivered during the MVC and at rest to calculate the level of voluntary activation and the resting doublet twitch. After the race, decreases in MVC force (males: −11%, effect size [ES] 0.52; females: −11% ES 0.33), voluntary activation (males: −6%, ES 0.87; females: −4%, ES 0.72), and resting doublet twitch (males: −6%, ES 0.34; females: −8%, ES 0.30) were found to be similar between males and females. The decrease in peak RFD was found to be similar between males and females (males: −14%, ES 0.43; females: −15%, ES 0.14). Half‐marathon run induced both central and peripheral fatigue, without any difference between men and women. The maximal and explosive strength loss was found similar between sexes. Together, these findings do not support the need of sex‐specific training interventions to increase the tolerance to neuromuscular fatigue in half‐marathoners.
An ordered pattern of Ana2 phosphorylation by Plk4 is required for centriole assembly
Authors: McLamarrah Tiffany A. , Buster Daniel W. , Galletta Brian J. , Boese Cody J. , Ryniawec John M. , Hollingsworth Natalie Ann , Byrnes Amy E. , Brownlee Christopher W. , Slep Kevin C. , Rusan Nasser M. , Rogers Gregory C.
Published: March 2018

Polo-like kinase 4 (Plk4) initiates an early step in centriole assembly by phosphorylating Ana2/STIL, a structural component of the procentriole. Here, we show that Plk4 binding to the central coiled-coil (CC) of Ana2 is a conserved event involving Polo-box 3 and a previously unidentified putative CC located adjacent to the kinase domain. Ana2 is then phosphorylated along its length. Previous studies showed that Plk4 phosphorylates the C-terminal STil/ANa2 (STAN) domain of Ana2/STIL, triggering binding and recruitment of the cartwheel protein Sas6 to the procentriole assembly site. However, the physiological relevance of N-terminal phosphorylation was unknown. We found that Plk4 first phosphorylates the extreme N terminus of Ana2, which is critical for subsequent STAN domain modification. Phosphorylation of the central region then breaks the Plk4–Ana2 interaction. This phosphorylation pattern is important for centriole assembly and integrity because replacement of endogenous Ana2 with phospho-Ana2 mutants disrupts distinct steps in Ana2 function and inhibits centriole duplication.
Fermentative utilization of glycerol residue for the production of acetic acid
Authors: Irvan  , Trisakti B , Hasibuan R , Joli M
Published: March 2018

Glycerol residue, frequently known as pitch, is a waste produced from the downstream product of crude glycerine distillation. With the increasing need of pure glycerine in the world, the glycerol residue produced is also increasing. Glycerol residue is a solid waste at room temperature, highly alkaline (pH > 13), corrosive, and categorized as hazardous and poisonous waste. In this research, acetic acid was produced from glycerol residue through the anaerobic fermentation process by using purple non-sulphur photosynthetic bacteria. The purpose of this study was to find out the influence of concentration change of glycerol residue on time and to find out the possibility of glycerol residue to be utilized as acetic acid. In this research, at first 400 g of glycerol residue was diluted with 200 ml of distilled water to change the glycerine phase, from solid to liquid at room temperature, acidified by using hydrochloric acid until pH 2. The top layer formed was fatty acid and triglycerides that should be removed. Meanwhile, the bottom layer was diluted glycerol residue which was then neutralized with caustic soda. To produce acetic acid, glycerol residue with various concentrations, salt, and purple non-sulphur photosynthetic bacteria were put together into a 100 ml bottle which had been previously sterilized, then incubated for four weeks under the light of 40-watt bulb. The result showed that on the 28th day of fermentation, the produced acetic acid were 0.28, 1.85, and 0.2% (w/w) by using glycerine with the concentration of 0.5, 1.0, and 1.5% (w/w), respectively.
State of the Art Control Measures for Aluminium Fade and SEN Clogging during Steelmaking Operations
Authors: Kamaraj Ashok , Saravanakumar R , Rajaguru M
Published: March 2018

Crack formation, fatigue failure of components and other process interruptions in liquid steel practices such as ladle nozzle clogging, SEN clogging, break outs are mainly due to residual deoxidation products such as alumina present in steels. The present paper deals with the issues in steel processing operations and provides state-of-the-art control measures for clean steel production. Investigations regarding the residual alumina content and its consequences at integrated steel plant shows that, Al-fade of maximum 0.02% is observed, which produces equivalent of 37 Kg of alumina in the liquid steel. Furthermore, slag carry over, re-oxidation, improper argon rinsing practice, aluminium consumption at secondary steelmaking practices also influences the alumina formation during steelmaking practices. The residual alumina not only affects the quality of steel, but also results in process interruptions such as ladle choking, SEN choking, subsequent break outs etc. various steelmaking practices influences clogging and aluminium fade are discussed and possible suggestions are given to improve the cleanliness of steel.
Perioral Rejuvenation: A Prospective, Quantitative Dynamic Three-Dimensional Analysis of a Dual Modality Treatment
Authors: Chang Catherine S , Chang Brian L , Lanni Michael , Wilson Anthony J , Beer Jacob , Percec Ivona
Published: March 2018

Background

The perioral region is the most dynamic anatomic area of the face and subject to complex and dramatic changes during aging. Successful treatment for perioral rejuvenation has yet to be identified, and prior studies have reported only subjective outcomes.

Objectives

The purpose of this study was to utilize our validated dynamic 3-dimensional imaging technology to determine whether conservative neuromodulation combined with hyaluronic acid filler volumization can decrease perioral strain and increase volume with significant patient satisfaction.

Methods

An IRB-approved prospective study of a dual modality treatment for perioral rhytids was performed on females with perioral aging who had not had prior facial treatment within the past year. Eighteen (18) units of Dysport were injected into the upper and lower orbicularis oris and 1 cc of Restylane Silk was injected in volume-depleted perioral regions in each patient. Each patient underwent imaging with digital image correlation (DIC) and completed the FACE-Q survey prior to injection and at 14 days and 90 days postinjection.

Results

Thirty-two female patients were recruited. A significant reduction in perioral strain was observed at both day 14 and day 90. This was concomitant with a significant increase in perioral volume at day 14 that at 90 days was significantly retained in the marionette lines. Further, there was a significant improvement in patient satisfaction with overall facial appearance at day 14 that was maintained at 90 days.

Conclusions

Conservative neuromodulation and hyaluronic acid filler volumization of the perioral region produces a significant reduction in strain correlating with high patient satisfaction, even at 90 days. This dual modality treatment is effective in rejuvenating the perioral region, and its future optimization will provide greater therapeutic options for this anatomically complex area.

Level of Evidence: 4
Distinct telomere length and molecular signatures in seminoma and non-seminoma of testicular germ cell tumor
Authors: Sun Hua , Kim Pora , Jia Peilin , Park Ae Kyung , Liang Han , Zhao Zhongming
Published: March 2018

Testicular germ cell tumors (TGCTs) are classified into two main subtypes, seminoma (SE) and non-seminoma (NSE), but their molecular distinctions remain largely unexplored. Here, we used expression data for mRNAs and microRNAs (miRNAs) from The Cancer Genome Atlas (TCGA) to perform a systematic investigation to explain the different telomere length (TL) features between NSE (n = 48) and SE (n = 55). We found that TL elongation was dominant in NSE, whereas TL shortening prevailed in SE. We further showed that both mRNA and miRNA expression profiles could clearly distinguish these two subtypes. Notably, four telomere-related genes (TelGenes) showed significantly higher expression and positively correlated with telomere elongation in NSE than SE: three telomerase activity-related genes (TERT, WRAP53 and MYC) and an independent telomerase activity gene (ZSCAN4). We also found that the expression of genes encoding Yamanaka factors was positively correlated with telomere lengthening in NSE. Among them, SOX2 and MYC were highly expressed in NSE versus SE, while POU5F1 and KLF4 had the opposite patterns. These results suggested that enhanced expression of both TelGenes (TERT, WRAP53, MYC and ZSCAN4) and Yamanaka factors might induce telomere elongation in NSE. Conversely, the relative lack of telomerase activation and low expression of independent telomerase activity pathway during cell division may be contributed to telomere shortening in SE. Taken together, our results revealed the potential molecular profiles and regulatory roles involving the TL difference between NSE and SE, and provided a better molecular understanding of this complex disease.
MatrixEpistasis: ultrafast, exhaustive epistasis scan for quantitative traits with covariate adjustment
Authors: Zhu Shijia , Fang Gang
Published: March 2018

Motivation

For many traits, causal loci uncovered by genetic mapping studies explain only a minority of the heritable contribution to trait variation. Multiple explanations for this ‘missing heritability’ have been proposed. Single nucleotide polymorphism (SNP)–SNP interaction (epistasis), as one of the compelling models, has been widely studied. However, the genome-wide scan of epistasis, especially for quantitative traits, poses huge computational challenges. Moreover, covariate adjustment is largely ignored in epistasis analysis due to the massive extra computational undertaking.

Results

In the current study, we found striking differences among epistasis models using both simulation data and real biological data, suggesting that not only can covariate adjustment remove confounding bias, it can also improve power. Furthermore, we derived mathematical formulas, which enable the exhaustive epistasis scan together with full covariate adjustment to be expressed in terms of large matrix operation, therefore substantially improving the computational efficiency (∼104× faster than existing methods). We call the new method MatrixEpistasis. With MatrixEpistasis, we re-analyze a large real yeast dataset comprising 11 623 SNPs, 1008 segregants and 46 quantitative traits with covariates fully adjusted and detect thousands of novel putative epistasis with P-values < 1.48e-10.

Availability and implementation

The method is implemented in R and available at https://github.com/fanglab/MatrixEpistasis.

Supplementary information

Supplementary data are available at Bioinformatics online.
GAIT: Gene expression Analysis for Interval Time
Authors: Kim Yoojoong , Kang Yeong Seon , Seok Junhee
Published: March 2018

Motivation

Despite the potential usefulness, the association analysis of gene expression with interval times of two events has been hampered because the occurrence of events can be censored and the conventional survival analysis is not suitable to handle two censored events. However, the recent advances of multivariate survival analysis considering multiple censored events together provide an unprecedented chance for this problem. Based on such advances, we have developed a software tool, GAIT, for the association analysis of gene expression with interval time of two events.

Results

The performance of GAIT was demonstrated by simulation studies and the real data analysis. The result indicates the usefulness of GAIT in a wide range of biomedical applications.

Availability and implementation

http://cdal.korea.ac.kr/GAIT/index.html

Supplementary information

Supplementary data are available at Bioinformatics online.
GDCRNATools: an R/Bioconductor package for integrative analysis of lncRNA, miRNA and mRNA data in GDC
Authors: Li Ruidong , Qu Han , Wang Shibo , Wei Julong , Zhang Le , Ma Renyuan , Lu Jianming , Zhu Jianguo , Zhong Wei-De , Jia Zhenyu
Published: March 2018

Motivation

The large-scale multidimensional omics data in the Genomic Data Commons (GDC) provides opportunities to investigate the crosstalk among different RNA species and their regulatory mechanisms in cancers. Easy-to-use bioinformatics pipelines are needed to facilitate such studies.

Results

We have developed a user-friendly R/Bioconductor package, named GDCRNATools, for downloading, organizing and analyzing RNA data in GDC with an emphasis on deciphering the lncRNA-mRNA related competing endogenous RNAs regulatory network in cancers. Many widely used bioinformatics tools and databases are utilized in our package. Users can easily pack preferred downstream analysis pipelines or integrate their own pipelines into the workflow. Interactive shiny web apps built in GDCRNATools greatly improve visualization of results from the analysis.

Availability and implementation

GDCRNATools is an R/Bioconductor package that is freely available at Bioconductor (http://bioconductor.org/packages/devel/bioc/html/GDCRNATools.html). Detailed instructions, manual and example code are also available in Github (https://github.com/Jialab-UCR/GDCRNATools).
Preview tracking control for a class of discrete-time Lipschitz non-linear time-delay systems
Authors: Yu Xiao , Liao Fucheng
Published: March 2018

The design of a preview tracking controller for a class of discrete-time Lipschitz non-linear time-delay systems is considered in this paper. First, based on preview control theory, we introduce a difference operator and deduce an augmented error system which contains previewable information on the reference signal. The original tracking problem is thus transformed into a regulation problem. Second, we design a memory state feedback controller for the augmented error system. Applying Lyapunov’s second method, the sufficient condition for stability of the closed-loop system is derived in the form of linear matrix inequality (LMI), and the preview controller is obtained accordingly. Finally, to show the superiority of the controller proposed, two numerical examples are presented.
Pointwise Asymptotics for Orthonormal Polynomials at the Endpoints of the Interval via Universality
Authors: Lubinsky Doron S
Published: March 2018

We show that universality limits and other bounds imply pointwise asymptotics for orthonormal polynomials at the endpoints of the interval of orthonormality. As a consequence, we show that if $\mu $ is a regular measure supported on $\left [ -1,1\right ] $, and in a neighborhood of 1, $ \mu $ is absolutely continuous, while for some $\alpha>-1$, $\mu ^{\prime }\left ( t\right ) =h\left ( t\right ) \left ( 1-t\right )^{\alpha }$, where $ h\left ( t\right ) \rightarrow 1$ as $t\rightarrow 1-$, then the corresponding orthonormal polynomials $\left \{ p_{n}\right \} $ satisfy the asymptotic $$ \lim_{n\rightarrow \infty }\frac{p_{n}\left( 1-\frac{z^{2}}{2n^{2}}\right) }{ p_{n}\left( 1\right) }=\frac{J_{\alpha }^{\ast }\left( z\right) }{J_{\alpha }^{\ast }\left( 0\right) } $$uniformly in compact subsets of the plane. Here $J_{\alpha }^{\ast }\left ( z\right ) =J_{\alpha }\left ( z\right ) /z^{\alpha }$ is the normalized Bessel function of order $\alpha $. These are by far the most general conditions for such endpoint asymptotics.
Operationalizing International Regulatory Standards in a Limited-Resource Setting During an Epidemic: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) Experience
Authors: Kabineh Abdul Karim , Carr Wendy , Motevalli Mahnaz , Legardy-Williams Jennifer , Vincent Willietta , Mahon Barbara E , Samai Mohamed
Published: March 2018

International regulatory standards ensure human subjects protection, data quality, and scientific integrity of clinical trials. Operationalizing regulatory standards during a large vaccine clinical trial—the Sierra Leone Trial to Introduce a Vaccine Against Ebola—in a resource-constrained setting during an epidemic required flexibility and creativity. We highlight areas that required special attention, such as developing standard operating procedures appropriate for the setting, obtaining space and supplies for the regulatory office, and creating a strategy to maintain both a dedicated central regulatory office and satellite regulatory sites for this trial with paper-based records.

Clinical Trials Registration

ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].
Toward a normalized clinical drug knowledge base in China—applying the RxNorm model to Chinese clinical drugs
Authors: Wang Li , Zhang Yaoyun , Jiang Min , Wang Jingqi , Dong Jiancheng , Liu Yun , Tao Cui , Jiang Guoqian , Zhou Yi , Xu Hua
Published: March 2018

Objective

In recent years, electronic health record systems have been widely implemented in China, making clinical data available electronically. However, little effort has been devoted to making drug information exchangeable among these systems. This study aimed to build a Normalized Chinese Clinical Drug (NCCD) knowledge base, by applying and extending the information model of RxNorm to Chinese clinical drugs.

Methods

Chinese drugs were collected from 4 major resources—China Food and Drug Administration, China Health Insurance Systems, Hospital Pharmacy Systems, and China Pharmacopoeia—for integration and normalization in NCCD. Chemical drugs were normalized using the information model in RxNorm without much change. Chinese patent drugs (i.e., Chinese herbal extracts), however, were represented using an expanded RxNorm model to incorporate the unique characteristics of these drugs. A hybrid approach combining automated natural language processing technologies and manual review by domain experts was then applied to drug attribute extraction, normalization, and further generation of drug names at different specification levels. Lastly, we reported the statistics of NCCD, as well as the evaluation results using several sets of randomly selected Chinese drugs.

Results

The current version of NCCD contains 16 976 chemical drugs and 2663 Chinese patent medicines, resulting in 19 639 clinical drugs, 250 267 unique concepts, and 2 602 760 relations. By manual review of 1700 chemical drugs and 250 Chinese patent drugs randomly selected from NCCD (about 10%), we showed that the hybrid approach could achieve an accuracy of 98.60% for drug name extraction and normalization. Using a collection of 500 chemical drugs and 500 Chinese patent drugs from other resources, we showed that NCCD achieved coverages of 97.0% and 90.0% for chemical drugs and Chinese patent drugs, respectively.

Conclusion

Evaluation results demonstrated the potential to improve interoperability across various electronic drug systems in China.
Evaluation of the learning environment designed to develop student mathematics teachers’ mathematical modelling competencies
Authors: Aydin-Güç Funda , Baki Adnan
Published: March 2018

The purpose of this study was to examine the mathematical modelling competencies of student mathematics teachers within a learning environment that was based on a holistic approach to instruction. The participants were student mathematics teachers enrolled in undergraduate programmes at two different universities. In one of the university programmes, the participants took a mathematical modelling course that was taught according to a holistic approach, while the participants at the other university followed the standardized undergraduate programme that did not include a mathematical modelling course. The sub-competencies of mathematical modelling of the student mathematics teachers who participated in the mathematical modelling course were examined using an analytic rubric that was designed according to the holistic approach applied within the context of the study. In order to determine whether the observed changes were related to the experiences of mathematical modelling, these results were compared to the sub-competencies of mathematical modelling of the control group. The findings showed that experience within a learning environment based on mathematical modelling, as well as affective factors, supported the development of modelling competencies. On the other hand, it was observed that certain sub-competencies were difficult to develop; while many sub-competencies were enhanced by the modelling experiences, others were adversely affected. Furthermore, a certain group of sub-competencies was found not to be directly linked to modelling experiences.
Characterization of Monilinia spp. Populations on Stone Fruit in South Italy
Authors: Abate D. , Pastore C. , Gerin D. , De Miccolis Angelini R. M. , Rotolo C. , Pollastro S. , Faretra F.
Published: March 2018

Monilinia spp. are responsible for brown rot decay of stone and pome fruit in the field as well as in postharvest. Monilinia laxa and M. fructigena are considered indigenous to Europe, while M. fructicola is a quarantine pathogen in the European and Mediterranean Plant Protection Organization area included in the A2 List. In Italy, it was first reported in 2009 in Piedmont (northern Italy) and rapidly spread to central Italy. We carried out a monitoring program on the occurrence of Monilinia spp. in southern Italy and a comparative characterization of the three main fungal pathogens. Molecular assays based on direct polymerase chain reaction (PCR) and real-time quantitative PCR for molecular identification of Monilinia spp. from rotted fruit were set up, validated, and applied in a monitoring program. Of the tested 519 isolates from 26 orchards, 388 (74.8%) were identified as M. fructicola, 118 (22.7%) as M. laxa, 10 (1.9%) as M. fructigena, and 3 (0.6%) were M. polystroma. M. fructicola colonies grew faster and had a higher optimal temperature for growth (26°C) than M. laxa (23°C) and M. fructigena (20°C). No relevant difference in virulence could be observed on artificially inoculated apricot, cherry, and peach fruit. The fungal species showed different responses to fungicides, because M. fructicola was more sensitive than M. laxa, especially to cyflufenamid, and M. fructigena revealed a lower sensitivity to succinate dehydrogenase inhibitors (boscalid, fluopyram, and fluxapyroxad) and quinone outside inhibitors (mandestrobin). In summary, the two species M. fructicola and M. polystroma were first detected in southern Italy where M. fructicola has largely displaced the two indigenous pathogens M. laxa and M. fructigena; the relative proportions of the three pathogens in orchards should be considered when defining the management of brown rot of stone fruit due to differences in their responses to fungicides.
Combining Thermotherapy with Cryotherapy for Efficient Eradication ofApple stem grooving virusfrom Infected In-vitro-cultured Apple Shoots
Authors: Zhao Lei , Wang Min-Rui , Cui Zhen-Hua , Chen Long , Volk Gayle M. , Wang Qiao-Chun
Published: March 2018

Apple stem grooving virus (ASGV), a difficult-to-eradicate virus from apple propagative materials, causes serious damage to apple production. The use of virus-free plants has been and is an effective strategy for control of plant viral diseases. This study aimed to eradicate ASGV from virus-infected in-vitro-cultured shoots of four apple cultivars and one rootstock by combining thermotherapy with cryotherapy. In vitro stock shoots infected with ASGV were thermo-treated using an alternating temperature of 36°C (day) and 32°C (night). Shoot tips were excised from the treated stock shoots and subjected to cryotherapy. Results showed that, although thermotherapy did not influence shoot survival rates, it reduced shoot growth and proliferation of in vitro shoots. Shoot regrowth rates decreased while virus eradication frequencies increased in cryo-treated shoot tips as time durations of thermotherapy increased from 0 to 6 weeks. Shoot regrowth and frequency of virus eradication were positively and negatively correlated, respectively, with the size of shoot tips. The protocol established here yielded shoot regrowth rates and virus eradication frequencies of 33 to 76% and 30 to 100%, respectively, in the four apple cultivars and one rootstock. Thermotherapy altered virus distribution patterns, subsequently resulting in production of a larger virus-free area in the thermo-treated shoot tips. Many cells in the top layers of apical dome and some cells in the youngest leaf primordia survived in cryo-treated shoot tips; these cells were most likely free of virus infection. Thus, plants regenerated from the procedure of combining thermotherapy with cryotherapy were free of ASGV, as judged by reverse-transcription polymerase chain reaction. To the best of our knowledge, this is the widest-spectrum technique reported thus far for the production of ASGV-free plants and provides a novel biotechnology for the production of virus-free plants in Malus spp.
Structural Analysis of Tensor Tympani Muscle, Tympanic Diaphragm, Epitympanum, and Protympanum in Menière's Disease: a Human Temporal Bone Study
Authors: Azuma Takahiro , Nogaki Taketoshi , Schachern Patricia , Paparella Michael M. , Cureoglu Sebahattin
Published: March 2018

Hypothesis:

We hypothesized that there would be significant anatomic differences of the tensor tympani muscle (TTM), tympanic diaphragm, epitympanum, and protympanum in patients with versus without Menière's disease.

Background:

The effects of tenotomy on Menière's disease suggested it relieves the pressure on the inner ear of the contraction of the TTM and of negative middle ear pressure.

Methods:

Using human temporal bones from patients with Menière's disease, two studies were conducted. We examined the presence of otitis media, cholesteatoma, and endolymphatic hydrops, the length, diameter, configuration, the volume of the TTM and tendon, and the area of the tympanic isthmus (Study 1). We examined the presence of otitis media, cholesteatoma and endolymphatic hydrops, and the area and volume of the protympanum (Study 2).

Results:

In study 1, we observed no significant differences between the two groups. In study 2, we did not observe a small and narrow protympanum in the Menière's disease group. None of the ears in the Menière's or control groups had otitis media or cholesteatoma in either study. We observed hydrops in all the temporal bones of the Menière's disease group and none in the control groups.

Conclusion:

The position, configuration, and size of the tensor tympani muscle and tendon do not seem to play a role in the pathogenesis of Menière's disease. Because the tympanic isthmus and protympanum in Menière's disease are not smaller than controls and that none of the temporal bones had otitis media or cholesteatoma, it is unlikely that there was dysventilation in the middle ear.
Follow the Leader
Authors: Boothe Amy , Yoder-Wise Patricia , Gilder Richard
Published: March 2018

Almost every formal organization has a multilayered hierarchy. The role of the leader has been discussed in the literature for decades. Less well understood, and certainly less well documented, is the role of the follower. Followers make up the majority of any organization but have been overlooked as a worthy component of the team. The first step in breaking this mold is identifying the types of followership that are present within the nursing profession. A population of nurses with 4 or fewer years of experience in a designated hospital setting in Southwest Texas. A descriptive study, using a 20-question, 7-point (0-6) Likert-type, validated questionnaire, was changed to an electronic format in Qualtrics and used to survey the identified nursing population. Data collected within Qualtrics XM were exported into Excel and then into SPSS 20 IBM version that was then used to create a scatterplot. The 2 axes represented the independent thinking and the active engagement of the participants. Correlations between demographics and followership styles were also conducted, using a chi-square automatic interaction detector (CHAID) analysis. Using Robert E. Kelley's scatterplot to analyze the data, 3 different types of followers were identified within the respondents. The 3 types were exemplary followers, conformist followers, and pragmatist followers. Of the qualified participants who completed the questionnaire, the majority fell into the exemplary follower category. The results identified that an issue with active engagement exists among all of the participants.
Patterns of recurrence after curative-intent surgery for pancreas cancer reinforce the importance of locoregional control and adjuvant chemotherapy
Authors: Munir Rohan , Soreide Kjetil , Ravindran Rajan , Powell James J. , Harrison Ewen M. , Adair Anya , Wigmore Stephen J. , Parks Rowan W. , Garden O. James , Kirkpatrick Lorraine , Wall Lucy R , Christie Alan , Penman Ian , McAvoy Norma , Save Vicki , Stockman Alan , Worrall David , Ireland Hamish , Weir Graeme , Masson Neil , Hay Chris , Smith James-Gordon , Mole Damian J.
Published: March 2018

Introduction

The pattern of recurrence after surgical excision of pancreas cancer may guide alternative pre-operative strategies to either detect occult disease or need for chemotherapy. This study investigated patterns of recurrence after pancreatic surgery.

Methods

Recurrence patterns were described in a series of resected pancreas cancers over a 2-year period and recurrence risk expressed as odds ratio (OR) with 95% confidence interval (C.I.). Survival was displayed by Kaplan-Meier curves.

Results

Of 107 pancreas resections, 69 (65%) had pancreatic cancer. R0 resection was achieved in 21 of 69 (30.4%). Analysis was based on 66 patients who survived 30 days after surgery with median follow up 21 months. Recurrence developed in 41 (62.1%) patients with median time to first recurrence of 13.3 months (interquartile range 6.9, 20.8 months). Recurrence site was most frequently locoregional (n=28, 42%), followed by liver (n=23, 35%), lymph nodes (n=21, 32%), and lungs (n=13, 19%). In patients with recurrence, 9 of 41 had single site recurrence; the remaining 32 patients had more than one site of recurrence. Locoregional recurrence was associated with R+ resection (53% vs 25% for R+ vs R0, respectively; OR 3.5, 95% C.I. 1.1-11.2; P=0.034). Venous invasion was associated with overall recurrence risk (OR 3.3, 95% C.I. 1.1-9.4; P=0.025). In multivariable analysis, R-stage and adjuvant chemotherapy predicted longer survival.

Discussion

The predominant locoregional recurrence pattern, multiple sites of recurrence and a high R+ resection rate reflect the difficulty in achieving initial local disease control.
MtMOT1.2 is responsible for molybdate supply toMedicago truncatulanodules
Authors: Gil-Díez Patricia , Tejada-Jiménez Manuel , León-Mediavilla Javier , Wen Jiangqi , Mysore Kirankumar S. , Imperial Juan , Gonzalez-Guerrero Manuel
Published: March 2018

Symbiotic nitrogen fixation in legume root nodules requires a steady supply of molybdenum for synthesis of the iron-molybdenum cofactor of nitrogenase. This nutrient has to be provided by the host plant from the soil, crossing several symplastically disconnected compartments through molybdate transporters, including members of the MOT1 family. MtMOT1.2 is aMedicago truncatulaMOT1 family member located in the endodermal cells in roots and nodules. Immunolocalization of a tagged MtMOT1.2 indicates that it is associated to the plasma membrane and to intracellular membrane systems, where it would be transporting molybdate towards the cytosol, as indicated in yeast transport assays. A loss-of-functionmot1.2-1mutant showed reduced growth compared to wild-type plants when nitrogen fixation was required, but not when nitrogen was provided as nitrate. While no effect on molybdenum-dependent nitrate reductase activity was observed, nitrogenase activity was severely affected, explaining the observed difference of growth depending on nitrogen source. This phenotype was the result of molybdate not reaching the nitrogen-fixing nodules, since genetic complementation with a wild-typeMtMOT1.2gene or molybdate-fortification of the nutrient solution, both restored wild-type levels of growth and nitrogenase activity. These results support a model in which MtMOT1.2 would mediate molybdate delivery by the vasculature into the nodules.
A novel xenograft model reveals invasive mesenchymal transition and ineffective angiogenic response during anti-angiogenic therapy resistance
Authors: Jahangiri Arman , Chen William , Chandra Ankush , Nguyen Alan , Yagnik Garima , Weiss Jacob , Wolf Kayla J. , Lin Jung-Ming G. , Mueller Soeren , Rick Jonathan , Sidorov Maxim , Flanigan Patrick , Carbonell W. Shawn , Diaz Aaron , Gilbert Luke , Kumar Sanjay , Aghi Manish K.
Published: March 2018

Bevacizumab treatment of glioblastoma is limited by transient responses and acquired resistance. Because of the lengthy duration of treatment that can precede resistance in patients, in order to study changes underlying the evolution of bevacizumab resistance, we created a novel multigenerational xenograft model of acquired bevacizumab resistance. Glioblastoma xenografts were treated with bevacizumab or IgG, and the fastest growing tumor re-implanted into new mice, generating paired isogeneic responsive or resistant multigenerational xenografts. Microarray analysis revealed significant overexpression across generations of the mesenchymal subtype gene signature, paralleling results from patient bevacizumab-resistant glioblastomas (BRGs) that exhibited increasing mesenchymal gene expression correlating with increased bevacizumab treatment duration. Key mesenchymal markers, including YKL-40, CD44, SERPINE1, and TIMP1 were upregulated across generations, with altered morphology, increased invasiveness, and increased neurosphere formation confirmed in later xenograft generations. Interestingly, YKL-40 levels were elevated in serum of patients with bevacizumab-resistant vs. bevacizumab-naïve glioblastomas. Finally, despite upregulation of VEGF-independent pro-angiogenic genes across xenograft generations, immunostaining revealed increased hypoxia and decreased vessel density with increasing generation of treatment, mirroring our findings in patient BRGs and suggesting tumor growth despite effective devascularization caused by VEGF blockade. Besides identifying novel targets for preventing the evolution of resistance and offering a xenograft model for testing resistance inhibitors, our work suggests YKL-40 as a blood biomarker of bevacizumab resistance worthy of further evaluation.
Intrinsic limitations in mainstream methods of identifying network motifs in biology
Authors: Fodor James , Brand Michael , Stones Rebecca J , Buckle Ashley M
Published: March 2018

Network motifs are connectivity structures that occur with significantly higher frequency than chance, and are thought to play important roles in complex biological networks, for example in gene regulation, interactomes, and metabolomes. Network motifs may also become pivotal in the rational design and engineering of complex biological systems underpinning the field of synthetic biology. Distinguishing true motifs from arbitrary substructures, however, remains a challenge. Here we demonstrate both theoretically and empirically that implicit assumptions present in mainstream methods for motif identification do not necessarily hold, with the ramification that motif studies using these mainstream methods are less able to effectively differentiate between spurious results and events of true statistical significance than is often presented. We show that these difficulties cannot be overcome without revising the methods of statistical analysis used to identify motifs. The implications of these findings are therefore far-reaching across diverse areas of biology.
Comprehensive Genetic Testing for Female and Male Infertility UsingNext Generation Sequencing
Authors: Patel Bonny , Parets Sasha , Akana Matthew , Kellogg Gregory , Jansen Michael , Chang Chihyu , Cai Ying , Fox Rebecca , Niknazar Mohammad , Shraga Roman , Hunter Colby , Pollock Andrew , Wisotzkey Robert , Jaremko Malgorzata , Bisignano Alex , Puig Oscar
Published: March 2018

Objective

To develop a comprehensive genetic test for female and male infertility in support of medical decisions during assisted reproductive technology (ART) protocols.

Design

Retrospective analysis of results from 118 DNA samples with known variants in loci representative of female and male infertility.

Interventions(s)

None

Main Outcome Measure(s)

Next-Generation Sequencing (NGS) of 87 genes including promoters, 5’ and 3’ untranslated regions, exons and selected introns. In addition, sex chromosome aneuploidies and Y chromosome microdeletions are analyzed concomitantly using the same panel.

Results

Analytical accuracy was >99%, with >98% sensitivity for Single Nucleotide Variants (SNVs) and >91% sensitivity for insertions/deletions (indels). Clinical sensitivity was assessed with samples containing variants representative of male and female infertility, and it was 100% for SNVs/indels, CFTR IVS8-5T variants, sex chromosome aneuploidies and Copy Number Variants (CNVs), and >93% for Y chromosome microdeletions. Cost analysis comparing the NGS assay with standard, multiple analysis approach, shows potential savings of $2723 per case. Conclusion: A single, comprehensive, NGS panel can simplify the ordering process for healthcare providers, reduce turnaround time, and lower the overall cost of testing for genetic assessment of infertility in females and males, while maintaining accuracy.
Evidence for a unique DNA-dependent RNA polymerase in cereal crops
Authors: Trujillo Joshua T. , Seetharam Arun S. , Hufford Matthew B. , Beilstein Mark A. , Mosher Rebecca A.
Published: March 2018

Gene duplication is an important driver for the evolution of new genes and protein functions. Duplication of DNA-dependent RNA polymerase (Pol) II subunits within plants led to the emergence of RNA Pol IV and V complexes, each of which possess unique functions necessary for RNA-directed DNA Methylation. Comprehensive identification of Pol V subunit orthologs across the monocot radiation revealed a duplication of the largest two subunits within the grasses (Poaceae), including critical cereal crops. These paralogous Pol subunits display sequence conservation within catalytic domains, but their carboxy terminal domains differ in length and character of the Ago-binding platform, suggesting unique functional interactions. Phylogenetic analysis of the catalytic region indicates positive selection on one paralog following duplication, consistent with retention via neofunctionalization. Positive selection on residue pairs that are predicted to interact between subunits suggests that paralogous subunits have evolved specific assembly partners. Additional Pol subunits as well as Pol-interacting proteins also possess grass-specific paralogs, supporting the hypothesis that a novel Pol complex with distinct function has evolved in the grass family, Poaceae.

Graphical Abstract

Significance statement

The grass family is critically important for humans, as this group contains cereal grains such as rice, wheat, and corn that form the bulk of the human diet. Here we provide evidence that grasses have evolved a unique polymerase complex of unknown function, suggesting a novel mechanism of gene regulation in the grass lineage. In addition to implications for the biology of grasses, this system offers an opportunity to understand how evolution shapes multi-subunit complexes through duplication of individual components.
Adaptive Reduction of Male Gamete Number in a Selfing Species
Authors: Tsuchimatsu Takashi , Kakui Hiroyuki , Yamazaki Misako , Marona Cindy , Tsutsui Hiroki , Hedhly Afif , Meng Dazhe , Sato Yutaka , Städler Thomas , Grossniklaus Ueli , Kanaoka Masahiro M. , Lenhard Michael , Nordborg Magnus , Shimizu Kentaro K.
Published: March 2018

The number of male gametes produced is critical for reproductive success and varies greatly between and within species1–3. Evolutionary reduction of male gamete production has been widely reported in plants as a hallmark of the selfing syndrome, as well as in humans. Such a reduction may simply represent deleterious decay4–7, but evolutionary theory predicts that breeding systems could act as a major selective force on male gamete number: while large numbers of sperm should be produced in highly promiscuous species because of male–male gamete competition1, reduced sperm numbers may be advantageous at lower outcrossing rates because of the cost of gamete production. Here we used genome-wide association study (GWAS) to show a signature of polygenic selection on pollen number in the predominantly selfing plantArabidopsis thaliana. The top associations with pollen number were significantly more strongly enriched for signatures of selection than those for ovule number and 107 phenotypes analyzed previously, indicating polygenic selection8. Underlying the strongest association, responsible for 20% of total pollen number variation, we identified the geneREDUCED POLLEN NUMBER 1affecting cell proliferation in the male germ line. We validated its subtle but causal allelic effects using a quantitative complementation test with CRISPR-Cas9-generated null mutants in a nonstandard wild accession. Our results support polygenic adaptation underlying reduced male gamete numbers.