bluuebunny/crossref_metadata_2025 huggingface dataset:
STRAP Acts as a Scaffolding Protein in Controlling the TLR2/4 Signaling Pathway
Authors: Huh Hyunbin D. , Ra Eun A. , Lee Taeyun A. , Kang Sujin , Park Areum , Lee Eunhye , Choi Junhee L. , Jang Eunji , Lee Ji Eun , Lee Sungwook , Park Boyoun
Published: December 2016

The WD40-repeat protein serine/threonine kinase receptor-associated protein (STRAP) is involved in the regulation of several biological processes, including cell proliferation and apoptosis, in response to various stresses. Here, we show that STRAP is a new scaffold protein that functions in Toll-like receptor (TLR)-mediated immune responses. STRAP specifically binds transforming growth factor β-activated kinase 1 (TAK1) and IκB kinase alpha (IKKα) along with nuclear factor-κB (NF-κB) subunit p65, leading to enhanced association between TAK1, IKKα, and p65, and subsequent facilitation of p65 phosphorylation and nuclear translocation. Consequently, the depletion of STRAP severely impairs interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-1β production, whereas its overexpression causes a significant increase in the secretion of these pro-inflammatory cytokines by TLR2 or TLR4 agonist-stimulated macrophages. Notably, STRAP translocates to the nucleus and subsequently binds to NF-κB at later times after lipopolysaccharide (LPS) stimulation, resulting in prolonged IL-6 mRNA production. Moreover, the C-terminal region of STRAP is essential for its functional activity in facilitating IL-6 production. Collectively, these observations suggest that STRAP acts as a scaffold protein that positively contributes to innate host defenses against pathogen infections.
High-throughput compound evaluation on 3D networks of neurons and glia in a microfluidic platform
Authors: Wevers Nienke R. , van Vught Remko , Wilschut Karlijn J. , Nicolas Arnaud , Chiang Chiwan , Lanz Henriette L. , Trietsch Sebastiaan J. , Joore Jos , Vulto Paul
Published: December 2016

With great advances in the field of in vitro brain modelling, the challenge is now to implement these technologies for development and evaluation of new drug candidates. Here we demonstrate a method for culturing three-dimensional networks of spontaneously active neurons and supporting glial cells in a microfluidic platform. The high-throughput nature of the platform in combination with its compatibility with all standard laboratory equipment allows for parallel evaluation of compound effects.
Association between gut microbiota and diapause preparation in the cabbage beetle: a new perspective for studying insect diapause
Authors: Liu Wen , Li Yi , Guo Shuang , Yin Han , Lei Chao-Liang , Wang Xiao-Ping
Published: December 2016

Gut microbiota mediate the nutritional metabolism and play important roles in human obesity. Diapausing insects accumulate large fat reserves and develop obese phenotypes in order to survive unfavorable conditions. However, the possibility of an association between gut microbiota and insect diapause has not been investigated. We used the Illumina MiSeq platform to compare gut bacterial community composition in nondiapause- (i.e. reproductive) and diapause-destined female cabbage beetles,Colaphellus bowringi, a serious pest of vegetables in Asia. Based on variation in the V3-V4 hypervariable region of 16S ribosomal RNA gene, we identified 99 operational taxonomic units and 17 core microbiota at the genus level. The relative abundance of the bacterial community differed between reproductive and diapause-destined female adults. Gut microbiota associated with human obesity, includingBacteroidetes,Firmicutes, andProteobacteria, showed a good correlation with diapause. This association between gut microbiota and diapause in the cabbage beetle may open a new avenue for studying insect diapause, as well as developing a natural insect obesity model with which to explore the mechanisms responsible for human obesity.
Determination of Br, Cl and I in honey using ICP-based techniques following microwave-assisted wet digestion with alkaline H2O2 in a single reaction chamber
Authors: Muller Edson I. , Souza Juliana P. , Anschau Kellen F. , Enders Michele S. P. , Muller Aline L. H. , Mortari Sergio R. , Duarte Fabio A.
Published: December 2016

A sample preparation method for further determination of halogens in honey using hydrogen peroxide in an alkaline medium in a high pressure system.
Hybrid porous bamboo-like CNTs embedding ultrasmall LiCrTiO4 nanoparticles as high rate and long life anode materials for lithium ion batteries
Authors: Tang Yakun , Liu Lang , Zhao Hongyang , Gao Shasha , Lv Yan , Kong Lingbing , Ma Junhong , Jia Dianzeng
Published: December 2016

Hybrid porous CNTs embedding ultrasmall LiCrTiO4 nanoparticles (6 ± 2 nm) were designed, which exhibited high reversible capacity, excellent rate capability and superior long-term cycling stability, especially at high current densities.
DNA–affibody nanoparticles for inhibiting breast cancer cells overexpressing HER2
Authors: Zhang Yanmin , Jiang Shuoxing , Zhang Dongdong , Bai Xiaoguang , Hecht Sidney M. , Chen Shengxi
Published: December 2016

A DNA tetrahedron–affibody–drug nanoparticle is a highly efficient tool to deliver doxorubicin (DOX) to HER2 overexpressing cancer cells specifically. It represents a highly efficacious agent for selectively inhibiting cancer cells which overexpress HER2 receptor.
Facilitated embedding of silver nanowires into conformally-coated iCVD polymer films deposited on cloth for robust wearable electronics
Authors: Seo Ji-Won , Joo Munkyu , Ahn Jaeho , Lee Tae-Ik , Kim Taek-Soo , Im Sung Gap , Lee Jung-Yong
Published: December 2016

A robust silver nanowire network is achieved on cloth by a spontaneous embedding process in an initiated vapor chemical deposition copolymer.
Advances in polymeric materials for dental applications
Authors: Xu Xinyuan , He Libang , Zhu Bengao , Li Jiyao , Li Jianshu
Published: December 2016

This review focuses on the relationship between the structures and properties of various polymers for different applications in dentistry.
Deubiquitylating enzymes in receptor endocytosis and trafficking
Authors: McCann Aidan P. , Scott Christopher J. , Van Schaeybroeck Sandra , Burrows James F.
Published: December 2016

In recent times, our knowledge of the roles ubiquitin plays in multiple cellular processes has expanded exponentially, with one example being the role of ubiquitin in receptor endocytosis and trafficking. This has prompted a multitude of studies examining how the different machinery involved in the addition and removal of ubiquitin can influence this process. Multiple deubiquitylating enzymes (DUBs) have been implicated either in facilitating receptor endocytosis and lysosomal degradation or in rescuing receptor levels by preventing endocytosis and/or promoting recycling to the plasma membrane. In this review, we will discuss in detail what is currently known about the role of DUBs in regulating the endocytosis of various transmembrane receptors and ion channels. We will also expand upon the role DUBs play in receptor sorting at the multivesicular body to determine whether a receptor is recycled or trafficked to the lysosome for degradation. Finally, we will briefly discuss how the DUBs implicated in these processes may contribute to the pathogenesis of a range of diseases, and thus the potential these have as therapeutic targets.
Verbal Working Memory in Older Adults: The Roles of Phonological Capacities and Processing Speed
Authors: Nittrouer Susan , Lowenstein Joanna H. , Wucinich Taylor , Moberly Aaron C.
Published: December 2016

Purpose

This study examined the potential roles of phonological sensitivity and processing speed in age-related declines of verbal working memory.

Method

Twenty younger and 25 older adults with age-normal hearing participated. Two measures of verbal working memory were collected: digit span and serial recall of words. Processing speed was indexed using response times during those tasks. Three other measures were also obtained, assessing phonological awareness, processing, and recoding.

Results

Forward and reverse digit spans were similar across groups. Accuracy on the serial recall task was poorer for older than for younger adults, and response times were slower. When response time served as a covariate, the age effect for accuracy was reduced. Phonological capacities were equivalent across age groups, so we were unable to account for differences across age groups in verbal working memory. Nonetheless, when outcomes for only older adults were considered, phonological awareness and processing speed explained significant proportions of variance in serial recall accuracy.

Conclusion

Slowing in processing abilities accounts for the primary trajectory of age-related declines in verbal working memory. However, individual differences in phonological capacities explain variability among individual older adults.
The Impact of Social–Cognitive Stress on Speech Variability, Determinism, and Stability in Adults Who Do and Do Not Stutter
Authors: Jackson Eric S. , Tiede Mark , Beal Deryk , Whalen D. H.
Published: December 2016

Purpose

This study examined the impact of social–cognitive stress on sentence-level speech variability, determinism, and stability in adults who stutter (AWS) and adults who do not stutter (AWNS). We demonstrated that complementing the spatiotemporal index (STI) with recurrence quantification analysis (RQA) provides a novel approach to both assessing and interpreting speech variability in stuttering.

Method

Twenty AWS and 21 AWNS repeated sentences in audience and nonaudience conditions while their lip movements were tracked. Across-sentence variability was assessed via the STI; within-sentence determinism and stability were assessed via RQA.

Results

Compared with the AWNS, the AWS produced speech that was more variable across sentences and more deterministic and stable within sentences. Audience presence contributed to greater within-sentence determinism and stability in the AWS. A subset of AWS who were more susceptible to experiencing anxiety exhibited reduced across-sentence variability in the audience condition compared with the nonaudience condition.

Conclusions

This study extends the assessment of speech variability in AWS and AWNS into the social–cognitive domain and demonstrates that the characterization of speech within sentences using RQA is complementary to the across-sentence STI measure. AWS seem to adopt a more restrictive, less flexible speaking approach in response to social–cognitive stress, which is presumably a strategy for maintaining observably fluent speech.
Grid‐to‐place cells model based on radial basis function network
Authors: Zhou Yang , Wu De‐wei
Published: December 2016

A novel model of grid cells (GCs) to place cells (PCs) based on radial basis function network (RBFN) is proposed. The connection between multi‐scale GCs and a PC is established through RBFN. For each PC, it is associated with a learned RBFN. During vehicle's space exploration, PCs and RBFNs are recruited flexibly after analysing the firing status of the existing PCs, and the transformation from GCs to a new PCs is learned for encoding a new location. As a result, PCs are generated incrementally to represent the explored space. Simulation results validate the proposed model is effective, and the firing characteristic of generated PCs is similar to that of biological PCs.
Direct detection of a fast modulated terahertz light with a spectrally matched quantum‐well photodetector
Authors: Tan Zhiyong , Li Hua , Wan Wenjian , Fu Zhanglong , Wang Chang , Cao Juncheng
Published: December 2016

A fast detection system based on a terahertz quantum‐well photodetector (QWP) and a fast modulated terahertz quantum‐cascade laser is presented. Response waveforms and eye diagrams under different modulation frequencies are acquired. Employing the current measurement system without any high speed optimisation obtains the highest response rate of 0.5 GHz. The experiment demonstrates that the QWP is potentially useful for fast detection and high speed communication applications.
Improving the timing accuracy of SiPMs by time‐walk compensation
Authors: Acconcia Giulia , Cariaggi Davide , Labanca Ivan , Rech Ivan , Ghioni Massimo
Published: December 2016

Timing measurements with silicon photomultipliers (SiPMs) are affected by the major issue of the so‐called time‐walk effect; this is due to the intrinsic architecture of SiPM devices. A new technique for time‐walk compensation in timing measurements with SiPMs is presented and discussed, feasible with a low‐complexity and low‐cost circuitry and able to improve the timing accuracy. The validity of the presented technique has been experimentally proven with a 3 × 3 mm2 Hamamatsu MPPC, achieving a jitter reduction of a factor 2.85 compared with the case without time‐walk compensation. To perform the experimental validation, a discrete‐components transimpedance amplifier is developed with large bandwidth and low jitter, specifically designed to read‐out and amplify the SiPM signal.
Event‐triggered consensus of non‐linear multi‐agent systems with sampling data and time delay
Authors: Su Housheng , Wang Zhaojing , Song Zhuoyue , Chen Xuan
Published: December 2016

The sampled‐data based event‐triggered strategy for consensus of leader‐following multi‐agent systems with the input‐delay and non‐linear dynamics is studied. A novel event‐triggered transmission strategy is proposed, where the controller of each agent updates and the sampled‐data of each agent transmits to its neighbours' only at the agent's own triggering time instants. The measurement errors are defined based on the state information of the local neighbourhood and leader to design the event triggering scheme, and this scheme reduces the number of event triggering times, the controller updating and communications between agents. Moreover, in the proposed event triggered control strategy, the Zeno‐behaviour is avoided. The control protocol and event triggering scheme can be simply designed by solving an LMI condition to achieve leader‐following consensus asymptotically. The effectiveness of the proposed results is demonstrated via a numerical example.
Individual and group tracking with the evaluation of social interactions
Authors: Yigit Ahmet , Temizel Alptekin
Published: December 2016

Tracking groups of people is a challenging problem. Groups may grow or shrink dynamically with merging and splitting of individuals and conventional trackers are not designed to handle such cases. In this study, the authors present a conjoint individual and group tracking (CIGT) framework based on particle filter and online learning. CIGT has four complementary phases: two‐phase association, false positive elimination, tracking and learning. First, reliable tracklets are created and detection responses are associated to tracklets in two‐phase association. Then, hierarchal false positive elimination is performed for unassociated detection responses. In the tracking phase, CIGT calculates multiple weights from the observation and jointly models individuals and groups. Particle advection is used in the motion model of CIGT to facilitate tracking of dense groups. In the learning phase, the discriminative appearance model, consisting of shape, colour and texture features, is extracted and used in AdaBoost online learning. Using the discriminative learning model, state estimation is performed on both individuals and groups. The experimental results show that the performance of the proposed framework compares favourably with other individual and group‐tracking methods for both real and synthetic datasets.
Radiation pattern synthesis for the generation of vortex electromagnetic wave
Authors: Liu Kang , Cheng Yongqiang , Wang Hongqiang , Li Xiang , Qin Yuliang
Published: December 2016

Radiation pattern synthesis methods for the generation of orbital angular momentum (OAM) beams based on circular arrays are proposed. The concentric‐ring arrays are designed to suppress the side lobes of the radiation pattern firstly. Based on the genetic algorithm, two objective functions are defined to calculate the signal amplitude of each ring. Simulation results show that the proposed method can effectively suppress the side lobes, lower than −30 dB. Subsequently, for electromagnetic vortex imaging, the beam steering technique is applied to enhance the directivity of vortex beams for different OAM modes. Analyses indicate that large steering angle would lead to some distortion of the phase‐front distribution. Finally, the imaging model after beam optimisation is established and the sparse Bayesian method is exploited to image the target with high resolution. The work can benefit the generation of OAM‐carrying beams and its wide applications in radio communication and radar imaging.
Frequency control by variable speed wind turbines in islanded power systems with various generation mix
Authors: Persson Mattias , Chen Peiyuan
Published: December 2016

This study presents the impact on power system frequency control in small power systems based on different generator topologies with a large penetration (50%) of variable speed wind turbines. The impact of a proposed controller is investigated versus various wind speeds. In particular, wind speeds with an average wind speed just below rated wind speed proves to cause the worst frequency fluctuations regardless of the type of backup generation topology investigated during 50% wind‐penetration ratio. For this wind‐speed session and a hydro‐based system, the proposed control system improves the frequency duration outside of the specified range [49.9, 50.1]Hz from 81 to 53% while reducing its delivered energy by only 6%. Furthermore, the proposed control reduces the absolute value of requested reserve by 49% from the hydro unit responsible for primary frequency control.
Intelligent grid interfaced solar water pumping system
Authors: Sharma Utkarsh , Singh Bhim , Kumar Shailendra
Published: December 2016

This study proposes a solar photovoltaic (SPV) water pumping system integrated with the single phase distribution system by utilising induction motor drive (IMD) with an intelligent power sharing concept. In addition to the power exchange from SPV to the IMD, a DC–DC boost converter is utilised as a power factor correction unit and a grid interfacing device. For good utilisation of SPV array, it is necessary to extract maximum power from the SPV array. To meet this objective, an incremental conductance based maximum power point tracking control is implemented. Whereas, to control the IMD tied to voltage source inverter, a simple voltage/frequency control technique is used. The proposed topology is designed and tested in the laboratory under standalone, grid interfaced and in mixed mode under various operating conditions.
Fabrication of Y2O3 microspheres by homogeneous precipitation method
Authors: Song Li , Li Junwei , Zhang Min , Zhang Baohang , Wang Jiaxin , Li Zhehui
Published: December 2016

Y2O3 microspheres were obtained via homogeneous precipitation method. Y2O3 microspheres with different sizes and morphologies were prepared by adjusting the reaction temperature, the concentration of ytterbium nitrate and urea (H2NCONH2), and the amount and species of surfactants. The structure and morphology of the as‐obtained Y2O3 were analysed by using X‐ray diffraction, scanning electron microscopy and transmission electron microscopy, and the results showed that the sample showed the optimal microscopy when it was prepared at 80°C with the concentration of ytterbium nitrate, H2NCONH2 and betaine fixed at 0.01 M, 0.04 M and 4 g/l, respectively. Moreover, the as‐prepared samples were uniform and smooth‐surfaced.
HNTs‐templated preparation of carbon nanorods by nanocasting method
Authors: Liu Zan , Cheng Zhi‐Lin , Liu Ying‐Ying
Published: December 2016

Carbon nanorods (CNRs) have been attracting increasing interest because of their potential applications in high‐performance nanoscale materials and electronic devices. Among the many preparation methods, the nanocasting method via inorganic template materials exhibited a controllable and facile feature. This work was to present a novel preparation of CNRs through the nanocasting method using halloysite nanotubes (HNTs) as the template and polyvinyl alcohol (PVA) as the nanocasting carbon source. For the sake of PVA nanocasted in the hollow structure of HNTs, we adopted the repeated soakage method. The forming process and structure of CNRs were revealed by XRD, FT‐IR, SEM, TEM, SAED XPS, Raman and Brunner–Emmet–Teller (BET) characterisation techniques. The results showed that the as‐obtained CNRs with the rod‐like structure had a high specific surface area of ca. 284 m2/g and exhibited typical mesoporous features.
The cleavage site preference of the porcine pepsin on the N-terminal α1 chain of bovine type I collagen: a focal analysis with mass spectrometry
Authors: Qian Jun , Ito Shinji , Satoh Junko , Geng Hongmin , Tanaka Keisuke , Hattori Shunji , Kojima Kenji , Takita Teisuke , Yasukawa Kiyoshi
Published: December 2016

Bovine type I collagen consists of two α1 and one α2 chains, containing the internal triple helical regions and the N- and C-terminal telopeptides. In industries, it is frequently digested with porcine pepsin to produce a triple helical collagen without the telopeptides. However, the digestion mechanism is not precisely understood. Here, we performed a mass spectrometric analysis of the pepsin digest of the N-terminal telopeptide pQLSYGYDEKSTGISVP (1–16) in the α1 chain. When purified collagen was digested, pQLSYGY (1–6) and pQLSYGYDEKSTG (1–12) were identified, while DEKSTG (7–12) was not. When the N-terminal telopeptide mimetic synthetic peptide pQLSK(MOCAc)GYDEKSTGISK(Dnp)P-NH2 was digested, pQLSK(MOCAc)GYDEKSTG (1–12) and ISK(Dnp)P-NH2 (13−16) were readily identified, pQLSK(MOCAc)GY (1−6) and DEKSTGISK(Dnp)P-NH2 (7−16) were weakly detected, and DEKSTG (7–12) was hardly identified. These results suggest that pepsin preferentially cleaves Tyr6–Asp7 and less preferentially Gly12–Ile13. They also suggest that the former cleavage requires native collagen structure, while the latter cleavage does not.
Constitutive centromere-associated network controls centromere drift in vertebrate cells
Authors: Hori Tetsuya , Kagawa Naoko , Toyoda Atsushi , Fujiyama Asao , Misu Sadahiko , Monma Norikazu , Makino Fumiaki , Ikeo Kazuho , Fukagawa Tatsuo
Published: December 2016

Centromeres are specified by sequence-independent epigenetic mechanisms, and the centromere position may drift at each cell cycle, but once this position is specified, it may not be frequently moved. Currently, it is unclear whether the centromere position is stable. To address this question, we systematically analyzed the position of nonrepetitive centromeres in 21 independent clones isolated from a laboratory stock of chicken DT40 cells using chromatin immunoprecipitation combined with massive parallel sequencing analysis with anti–CENP-A antibody. We demonstrated that the centromere position varies among the clones, suggesting that centromere drift occurs during cell proliferation. However, when we analyzed this position in the subclones obtained from one isolated clone, the position was found to be relatively stable. Interestingly, the centromere drift was shown to occur frequently in CENP-U– and CENP-S–deficient cells. Based on these results, we suggest that the centromere position can change after many cell divisions, but this drift is suppressed in short-term cultures, and the complete centromere structure contributes to the suppression of the centromere drift.
Machine learning and computer vision approaches for phenotypic profiling
Authors: Grys Ben T. , Lo Dara S. , Sahin Nil , Kraus Oren Z. , Morris Quaid , Boone Charles , Andrews Brenda J.
Published: December 2016

With recent advances in high-throughput, automated microscopy, there has been an increased demand for effective computational strategies to analyze large-scale, image-based data. To this end, computer vision approaches have been applied to cell segmentation and feature extraction, whereas machine-learning approaches have been developed to aid in phenotypic classification and clustering of data acquired from biological images. Here, we provide an overview of the commonly used computer vision and machine-learning methods for generating and categorizing phenotypic profiles, highlighting the general biological utility of each approach.
Lipid droplets are central organelles for meiosis II progression during yeast sporulation
Authors: Hsu Tzu-Han , Chen Rey-Huei , Cheng Yun-Hsin , Wang Chao-Wen
Published: December 2016

Neutral lipids, predominantly triacylglycerol (TAG) and sterol ester, are stored within the cellular organelles termed lipid droplets (LDs). Although it is believed that the major function of LDs is to supply the cell with energy and membranes, little is known about the cellular events directly involving LDs and their contents. In this study, we provide cytological evidence that LDs form direct contacts with the prospore membrane (PSM) that is synthesized de novo during meiosis II to sequester the dividing nuclei in sporulating yeast. Lipidomic analyses indicate that TAG lipolysis releases free fatty acids at a time that correlates well with meiosis II progression, concomitant with phospholipid remodeling. Mutants lacking TAG or impaired of TAG hydrolysis show spore wall assembly defects, supporting a role for TAG and/or its metabolites in spore wall morphogenesis. Not only does LD integrity influence spore wall assembly, LDs are also essential for other aspects of spore development. Yeast cells lacking LDs are severely defective in PSM growth and organization and display disrupted spindles, producing dead spores or even failing to form spores. Together these results link LD physiology directly to a unique membrane morphogenesis process critical for development.
Loss of a doublecortin (DCX)-domain protein causes structural defects in a tubulin-based organelle of Toxoplasma gondii and impairs host-cell invasion
Authors: Nagayasu Eiji , Hwang Yu-Chen , Liu Jun , Murray John M. , Hu Ke
Published: December 2016

The ∼6000 species in phylum Apicomplexa are single-celled obligate intracellular parasites. Their defining characteristic is the apical complex—membranous and cytoskeletal elements at the apical end of the cell that participate in host-cell invasion. The apical complex of Toxoplasma gondii and some other apicomplexans includes a cone-shaped assembly, the conoid, which in T. gondii comprises 14 spirally arranged fibers that are nontubular polymers of tubulin. The tubulin dimers of the conoid fibers make canonical microtubules elsewhere in the same cell, suggesting that nontubulin protein dictates their special arrangement in the conoid fibers. One candidate for this role is TgDCX, which has a doublecortin (DCX) domain and a TPPP/P25-α domain, both of which are known modulators of tubulin polymer structure. Loss of TgDCX radically disrupts the structure of the conoid, severely impairs host-cell invasion, and slows growth. Both the conoid structural defects and the impaired invasion of TgDCX-null parasites are corrected by reintroduction of a TgDCX coding sequence. The nontubular polymeric form of tubulin found in the conoid is not found in the host cell, suggesting that TgDCX may be an attractive target for new parasite-specific chemotherapeutic agents.
Intraflagellar transport-A complex mediates ciliary entry and retrograde trafficking of ciliary G protein–coupled receptors
Authors: Hirano Tomoaki , Katoh Yohei , Nakayama Kazuhisa
Published: December 2016

Cilia serve as cellular antennae where proteins involved in sensory and developmental signaling, including G protein–coupled receptors (GPCRs), are specifically localized. Intraflagellar transport (IFT)-A and -B complexes mediate retrograde and anterograde ciliary protein trafficking, respectively. Using a visible immunoprecipitation assay to detect protein–protein interactions, we show that the IFT-A complex is divided into a core subcomplex, composed of IFT122/IFT140/IFT144, which is associated with TULP3, and a peripheral subcomplex, composed of IFT43/IFT121/IFT139, where IFT139 is most distally located. IFT139-knockout (KO) and IFT144-KO cells demonstrated distinct phenotypes: IFT139-KO cells showed the accumulation of IFT-A, IFT-B, and GPCRs, including Smoothened and GPR161, at the bulged ciliary tips; IFT144-KO cells showed failed ciliary entry of IFT-A and GPCRs and IFT-B accumulation at the bulged tips. These observations demonstrate the distinct roles of the core and peripheral IFT-A subunits: IFT139 is dispensable for IFT-A assembly but essential for retrograde trafficking of IFT-A, IFT-B, and GPCRs; in contrast, IFT144 is essential for functional IFT-A assembly and ciliary entry of GPCRs but dispensable for anterograde IFT-B trafficking. Thus the data presented here demonstrate that the IFT-A complex mediates not only retrograde trafficking but also entry into cilia of GPCRs.
Food and Agricultural Industries: Opportunities for Improving Measurement and Reporting
Authors: Dunn Richard A. , Hueth Brent
Published: December 2016

We measure one component of off‐farm food and agricultural industries using establishment‐level microdata in the federal statistical system. We focus on services for crop production, and compare measures of firm and employment dynamics in this sector during the 1992–2012 time period with county‐level publicly available data for the same measures. Based on differences across data sources, we establish new facts regarding the evolution of food and agricultural industries, and demonstrate the value of working with confidential microdata. In addition to the data and results we present, we highlight possibilities for collaboration across universities and federal agencies to improve reporting in other segments of food and agricultural industries.
Algorithm sensitivity analysis and parameter tuning for tissue image segmentation pipelines
Authors: Teodoro George , Kurç Tahsin M , Taveira Luís F R , Melo Alba C M A , Gao Yi , Kong Jun , Saltz Joel H
Published: December 2016

Motivation

Sensitivity analysis and parameter tuning are important processes in large-scale image analysis. They are very costly because the image analysis workflows are required to be executed several times to systematically correlate output variations with parameter changes or to tune parameters. An integrated solution with minimum user interaction that uses effective methodologies and high performance computing is required to scale these studies to large imaging datasets and expensive analysis workflows.

Results

The experiments with two segmentation workflows show that the proposed approach can (i) quickly identify and prune parameters that are non-influential; (ii) search a small fraction (about 100 points) of the parameter search space with billions to trillions of points and improve the quality of segmentation results (Dice and Jaccard metrics) by as much as 1.42× compared to the results from the default parameters; (iii) attain good scalability on a high performance cluster with several effective optimizations.

Conclusions

Our work demonstrates the feasibility of performing sensitivity analyses, parameter studies and auto-tuning with large datasets. The proposed framework can enable the quantification of error estimations and output variations in image segmentation pipelines.

Availability and Implementation

Source code: https://github.com/SBU-BMI/region-templates/.

Supplementary information

Supplementary data are available at Bioinformatics online.
dAPE: a web server to detect homorepeats and follow their evolution
Authors: Mier Pablo , Andrade-Navarro Miguel A
Published: December 2016

Homorepeats are low complexity regions consisting of repetitions of a single amino acid residue. There is no current consensus on the minimum number of residues needed to define a functional homorepeat, nor even if mismatches are allowed. Here we present dAPE, a web server that helps following the evolution of homorepeats based on orthology information, using a sensitive but tunable cutoff to help in the identification of emerging homorepeats.

Availability and Implementation

dAPE can be accessed from http://cbdm-01.zdv.uni-mainz.de/∼munoz/polyx.

Supplementary information

Supplementary data are available at Bioinformatics online.
Improving Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) Treatment Monitoring in South Africa: Evaluation of an Advanced TB/HIV Course for Healthcare Workers
Authors: Galagan Sean , Jed Suzanne , Sumitani Jeri , Gilvydis Jennifer M. , Bakor Albert , Cooke Richard , Naidoo Evasen , Winters Debra , Weaver Marcia R.
Published: December 2016

Background

South Africa has dual epidemics of human immunodeficiency virus (HIV) and tuberculosis (TB). Nurse-focused training was combined with onsite mentoring for nurses to improve HIV and TB care. A pre-/postevaluation was conducted in 3 districts in South Africa to assess the effects of the course on clinical patient monitoring and integration of TB and HIV care.

Methods

Two cross-sectional, unmatched samples of patient charts at 76 primary healthcare facilities were collected retrospectively in 2014 to evaluate the impact of training on treatment monitoring. Proportions of HIV patients receiving a viral load test 6 months after initiating antiretroviral therapy (ART) and TB patients receiving end of intensive phase sputum testing were compared pre- and posttraining. Analysis of creatinine clearance testing and integration of TB and HIV care were also performed.

Results

Data were analyzed from 1074 pretraining and 1048 posttraining records among patients initiating ART and from 1063 pretraining and 1008 posttraining among patients initiating TB treatment. Documentation of a 6-month viral load test was 36.3%, and a TB test at end of intensive phase was 70.7%, and neither increased after training. Among patients with a viral load test, the percentage with viral load less than 50 copies/mL increased from 48.6% pretraining compared with 64.2% posttraining (P = .001). Integration of TB and HIV care such as isoniazid preventive therapy increased significantly.

Conclusions

The primary outcome measures did not change after training. However, the evaluation documented many other improvements in TB and HIV care that may have been supported by the course.
Isoflurane Sedation on the ICU in Cardiac Arrest Patients Treated With Targeted Temperature Management: An Observational Propensity-Matched Study
Authors: Krannich Alexander , Leithner Christoph , Engels Martin , Nee Jens , Petzinka Victor , Schröder Tim , Jörres Achim , Kruse Jan , Storm Christian
Published: December 2016

Objective:

Targeted temperature management after cardiac arrest requires deep sedation to prevent shivering and discomfort. Compared to IV sedation, volatile sedation has a shorter half-life and thus may allow more rapid extubation and neurologic assessment.

Design:

Observational analysis of clinical data.

Setting:

University hospital, medical ICU.

Patients:

Four hundred thirty-two cardiac arrest survivors underwent targeted temperature management; of those, 110 were treated with volatile sedation using an anesthetic conserving device and isoflurane, and 322 received standard IV sedation.

Intervention:

No intervention.

Measurement and Main Results:

A matched pairs analysis revealed that time on ventilator (difference of median, 98.5 hr; p = 0.003) and length of ICU stay (difference of median, 4.5 d; p = 0.006) were significantly shorter in patients sedated with isoflurane when compared with IV sedation although no differences in neurologic outcome (45% of patients with cerebral performance category 1–2 in both groups) were observed. Significant hypercapnia occurred more frequently during anesthetic conserving device use (6.4% vs 0%; p = 0.021).

Conclusions:

Volatile sedation is feasible in cardiac arrest survivors. Prospective controlled studies are necessary to confirm the beneficial effects on duration of ventilation and length of ICU stay observed in our study. Our data argue against a major effect on neurologic outcome. Close monitoring of Paco
2 is necessary during sedation via anesthetic conserving device.
Food and Drug Administration Efforts to Mitigate Contact Lens Discomfort
Authors: Hampton Denise , Green Joffre Angelo , Robboy Marc , Eydelman Malvina
Published: December 2016

The premarket review of contact lenses and accessories by the FDA involves the assessment of nonclinical and clinical information in support of clearance or approval of marketing applications. The review process for these medical devices, including attributes, which may contribute to comfort for lens wearers, is summarized, as are mechanisms by which FDA continues to assess and improve recommendations through the review process and through collaboration with external entities.
Characterization of the Corneal Subbasal Nerve Plexus in Limbal Stem Cell Deficiency
Authors: Chuephanich Pichaya , Supiyaphun Chantaka , Aravena Carolina , Bozkurt Tahir Kansu , Yu Fei , Deng Sophie X.
Published: December 2016

Purpose:

To quantify the changes in the subbasal nerve plexus in patients with limbal stem cell deficiency (LSCD) using in vivo laser scanning confocal microscopy.

Methods:

In this retrospective cross-sectional comparative study, confocal images of 51 eyes of 37 patients with LSCD collected between 2010 and 2015 by the Heidelberg Retina Tomograph III Rostock Corneal Module Confocal Microscope were analyzed. Two independent observers evaluated the scans of the central cornea. Seventeen normal eyes of 13 subjects served as controls. Total subbasal nerve density (SND), density of long nerves (ie, nerves 200 μm or longer), and the degree of tortuosity were quantified.

Results:

The mean (±SD) total SND and long nerve density were 48.0 ± 34.2 and 9.7 ± 10.9 nerves/mm2, respectively, in all eyes with LSCD and 97.3 ± 29.9 and 35.3 ± 25.3 nerves/mm2, respectively, in eyes of the control group (P < 0.001 for both comparisons). Compared with SND in control subjects, SND was reduced by 34.9% in the early stage, 54.0% in the intermediate stage, and 73.5% in the late stage of LSCD. The degrees of nerve tortuosity were significantly greater in patients with LSCD than in control subjects and differed among the early, intermediate, and late stages of LSCD. Reductions in total SND and long nerve density were positively correlated with the severity of LSCD.

Conclusions:

Reductions in total SND and long nerve density were accompanied by increases in nerve tortuosity in eyes with LSCD. These parameters could be used as quantifiable measures of LSCD severity.
Russian Keratoprosthesis in Stevens–Johnson Syndrome
Authors: Ma Xiao , Xiang Ran , Meng Xiaoli , Qin Limin , Wu Ying , Tain Lei , Jiang Yanming , Huang Yifei , Wang Liqing
Published: December 2016

Purpose:

To evaluate the efficacy and safety of Moscow Eye Microsurgery Complex in Russia (MICOF) keratoprosthesis (KPro) implantation in patients with Stevens–Johnson syndrome (SJS).

Methods:

This was a retrospective case series. Fourteen eyes of 13 patients with SJS underwent KPro implantation at the Chinese People's Liberation Army General Hospital between April 1, 2000, and December 24, 2014. The visual outcome, KPro retention rate, and incidence of postoperative complications and their management were recorded and investigated.

Results:

The mean age and follow-up duration were 61.5 ± 17.3 years (range: 27–87 yrs) and 62 ± 39.1 months (range: 13–144 mo). Thirteen eyes (92.9%) achieved a best-corrected visual acuity of 20/200 or better, and 8 eyes (57.1%) achieved a best-corrected visual acuity of 20/40 or better after surgery. However, 71.4% (10/14) experienced visual decline because of different postoperative complications. Common complications included corneal melting, glaucoma, vitritis, superficial tissue overgrowth, and retroprosthetic membrane, and the incidence of these complications was 71.4%, 28.6%, 35.7%, 14.3%, and 28.6%, respectively. After repair and autoauricular cartilage reinforcement, all cases had stable anatomical retention at the last visit.

Conclusions:

The MICOF KPro improved vision of patients with SJS, but lifelong surveillance is necessitated because of a high rate of postoperative complications. Corneal melting was the main reason for KPro failure. Infectious endophthalmitis and glaucoma were the main risk factors for visual loss.
Clinical Findings of Anterior Segment Spectral Domain Optical Coherence Tomography Images in Cytomegalovirus Corneal Endotheliitis
Authors: Kobayashi Reiko , Hashida Noriyasu , Soma Takeshi , Koh Shizuka , Miki Atsuya , Usui Shinichi , Maeda Naoyuki , Nishida Kohji
Published: December 2016

Purpose:

To evaluate the morphological characteristics of posterior corneal regions including keratic precipitates in eyes with cytomegalovirus (CMV) corneal endotheliitis using anterior segment spectral domain optical coherence tomography (SD-OCT).

Methods:

Thirteen eyes of 13 patients with polymerase chain reaction–proven CMV corneal endotheliitis were included in this study. Slit-lamp images and anterior segment SD-OCT images of the posterior cornea were obtained to analyze the clinical characteristics of corneal structures and keratic precipitates. Morphological changes in the posterior cornea throughout the course of an antiviral treatment were also investigated.

Results:

Anterior SD-OCT images showed protruding structures at the posterior cornea. These protruding structures exhibited dendritic, dome-shaped, quadrangular, or saw-tooth appearance, and reflectivity of these structures was high. Reflectivity of posterior corneal images including the endothelium and deep stromal corneal regions were also high (76.9%). Because corneal inflammation and corneal edema improved, the protruding structures and high-intensity regions of posterior corneal images were resolved after a course of antiviral treatment.

Conclusions:

The anterior segment SD-OCT examination represents a useful noninvasive alternative to diagnose and monitor CMV corneal endotheliitis.
The “Facemask Blinder”
Authors: Tsze Daniel S. , Woodward Hilary A.
Published: December 2016

We present the case of a 7-year-old boy with a forehead laceration that required suture repair. The child was anxious and uncooperative, and the initial plan was to administer intranasal midazolam to facilitate the repair. However, a facemask blinder was first implemented as a visual barrier to block the child’s view of any anxiety-provoking stimuli and appeared to improve the child’s cooperation with the procedure. Intranasal midazolam was not administered, and the laceration was cleaned and repaired successfully. In conjunction with adequate local anesthesia and distraction techniques, the facemask blinder helped to facilitate the completion of the laceration repair without the need for any physical restraint or pharmacologic anxiolysis or sedation.
PathogenicASXL1somatic variants in reference databases complicate germline variant interpretation for Bohring-Opitz Syndrome
Authors: Carlston Colleen M. , O’Donnell-Luria Anne H. , Underhill Hunter R. , Cummings Beryl B. , Weisburd Ben , Minikel Eric V. , Birnbaum Daniel P. ,   Exome Aggregation Consortium, Tvrdik Tatiana , MacArthur Daniel G. , Mao Rong
Published: December 2016

The interpretation of genetic variants identified during clinical sequencing has come to rely heavily on reference population databases such as the Exome Aggregation Consortium (ExAC). Genuinely pathogenic variants, particularly in genes associated with severe autosomal dominant conditions, are assumed to be absent or extremely rare in these databases. Clinical exome sequencing of a six-year-old female patient with seizures, global developmental delay, dysmorphic features and failure to thrive identified anASXL1variant that was previously reported as causative of Bohring-Opitz syndrome (BOS). Surprisingly, the variant was observed seven times in the ExAC database, presumably in individuals without BOS. Although the BOS phenotype matched the presentation of the patient, the presence of the variant in reference population databases introduced ambiguity in result interpretation. Interrogation of the literature revealed that acquired somatic mosaicism ofASXL1variants (including known pathogenic variants) during hematopoietic clonal expansion may be concomitant with aging in healthy individuals. We examined all high qualityASXL1predicted truncating variant calls in the ExAC database and determined the majority could be attributed to this phenomenon. Failure to consider somatic mosaicism may lead to the inaccurate assumption that conditions like Bohring-Opitz syndrome have reduced penetrance, or the misclassification of potentially pathogenic variants.
Recent evolution of extreme cestode growth suppression by a vertebrate host
Authors: Weber Jesse N. , Steinel Natalie C. , Chuan Shim Kum , Bolnick Daniel I.
Published: December 2016

Parasites can be a major cause of natural selection on hosts, which consequently evolve a variety of strategies to avoid, eliminate, or tolerate infection. When ecologically similar host populations present disparate infection loads, this natural variation can reveal immunological strategies underlying adaptation to infection and population divergence. For instance, the tapewormSchistocephalus soliduspersistently infects between 0% to 80% of threespine stickleback (Gasterosteus aculeatus) in lakes on Vancouver Island. To test whether these heterogeneous infection rates are due to evolved differences in immunity, we experimentally exposed lab-reared fish from high-and low-infection populations, which are not known to differ in natural exposure risk, to controlled doses ofSchistocephalus.We observed heritable between-population differences in several immune traits: fish from the naturally uninfected population initiated a stronger granulocyte response toSchistocephalusinfection, and their granulocytes constitutively generated threefold more reactive oxygen species (ROS). Despite these immunological differences,Schistocephaluswas equally successful at establishing initial infections in both host populations. However, the low-infection fish dramatically suppressed tapeworm growth relative to high-infection fish, and parasite size was intermediate in F1 hybrid hosts. Our results show that stickleback recently evolved heritable variation in their capacity to suppress helminth growth. Comparative data from many from natural populations indicate that growth suppression is widespread but not universal and, when present, is associated with reduced infection prevalence. Host suppression of helminth somatic growth may be an important immune strategy that aids in parasite clearance, or in mitigating the fitness costs of persistent infection.

Significance

Large parasites remain a persistent source of morbidity and mortality in humans, domesticated animals, and wildlife. Hosts are subject to strong natural selection to eliminate or tolerate these parasite infections. Here, we document the recent evolution of a striking form of resistance by a vertebrate host (threespine stickleback) against its cestode parasite (Schistocephalus solidus).After Pleistocene glacial retreat, marine stickleback colonized freshwater lakes, encounteredSchistocephalus, and evolved varying levels of resistance to it. We show that a heavily-and a rarely-infected population of stickleback have similar resistance toSchistocephaluscolonization, but rarely-infected fish suppress parasite growth by orders of magnitude. These populations represent ends of a natural continuum of cestode growth suppression, which is associated with reduced infection prevalence.
Lysine methyltransferase SETD6 modifies histones and non-histone proteins
Authors: Binda Olivier
Published: December 2016

Although central to regulating the access to genetic information, most lysine methyltransferases remain poorly characterised relative to other family of enzymes. Herein, we report new substrates for the lysine methyltransferase SETD6. Based on the SETD6- catalysed site on the histone variant H2AZ, we identified similar sequences in the canonical histones H2A, H3, and H4 that are modified by SETD6in vitro, and putative non-histone substrates. We herein expend the repertoire of substrates for methylation by SETD6.