bluuebunny/crossref_metadata_2025 huggingface dataset:
Hmong-Mien Languages
Authors: Mortensen David R.
Published: September 2017

Hmong-Mien (also known as Miao-Yao) is a bipartite family of minority languages spoken primarily in China and mainland Southeast Asia. The two branches, called Hmongic and Mienic by most Western linguists and Miao and Yao by Chinese linguists, are both compact groups (phylogenetically if not geographically). Although they are uncontroversially distinct from one another, they bear a strong mutual affinity. But while their internal relationships are reasonably well established, there is no unanimity regarding their wider genetic affiliations, with many Chinese scholars insisting on Hmong-Mien membership in the Sino-Tibetan superfamily, some Western scholars suggesting a relationship to Austronesian and/or Tai-Kradai, and still others suggesting a relationship to Mon-Khmer. A plurality view appears to be that Hmong-Mien bears no special relationship to any surviving language family.

Hmong-Mien languages are typical—in many respects—of the non-Sino-Tibetan languages of Southern China and mainland Southeast Asia. However, they possess a number of properties that make them stand out. Many neighboring languages are tonal, but Hmong-Mien languages are, on average, more so (in terms of the number of tones). While some other languages in the area have small-to-medium consonant inventories, Hmong-Mien languages (and especially Hmongic languages) often have very large consonant inventories with rare classes of sounds like uvulars and voiceless sonorants. Furthermore, while many of their neighbors are morphologically isolating, few language groups display as little affixation as Hmong-Mien languages. They are largely head-initial, but they deviate from this generalization in their genitive-noun constructions and their relative clauses (which vary in position and structure, sometimes even within the same language).
Bare Nominals
Authors: Le Bruyn Bert , de Swart Henriëtte , Zwarts Joost
Published: September 2017

Bare nominals (also called “bare nouns”) are nominal structures without an overt article or other determiner. The distinction between a bare noun and a noun that is part of a larger nominal structure must be made in context: Milk is a bare nominal in I bought milk, but not in I bought the milk. Bare nouns have a limited distribution: In subject or object position, English allows bare mass nouns and bare plurals, but not bare singular count nouns (*I bought table). Bare singular count nouns only appear in special configurations, such as coordination (I bought table and chairs for £182).

From a semantic perspective, it is noteworthy that bare nouns achieve reference without the support of a determiner. A full noun phrase like the cookies refers to the maximal sum of cookies in the context, because of the definite article the. English bare plurals have two main interpretations: In generic sentences they refer to the kind (Cookies are sweet), in episodic sentences they refer to some exemplars of the kind (Cookies are in the cabinet). Bare nouns typically take narrow scope with respect to other scope-bearing operators like negation.

The typology of bare nouns reveals substantial variation, and bare nouns in languages other than English may have different distributions and meanings. But genericity and narrow scope are recurring features in the cross-linguistic study of bare nominals.
A collaborative filtering-based approach to biomedical knowledge discovery
Authors: Lever Jake , Gakkhar Sitanshu , Gottlieb Michael , Rashnavadi Tahereh , Lin Santina , Siu Celia , Smith Maia , Jones Martin R , Krzywinski Martin , Jones Steven J M
Published: September 2017

Motivation

The increase in publication rates makes it challenging for an individual researcher to stay abreast of all relevant research in order to find novel research hypotheses. Literature-based discovery methods make use of knowledge graphs built using text mining and can infer future associations between biomedical concepts that will likely occur in new publications. These predictions are a valuable resource for researchers to explore a research topic. Current methods for prediction are based on the local structure of the knowledge graph. A method that uses global knowledge from across the knowledge graph needs to be developed in order to make knowledge discovery a frequently used tool by researchers.

Results

We propose an approach based on the singular value decomposition (SVD) that is able to combine data from across the knowledge graph through a reduced representation. Using cooccurrence data extracted from published literature, we show that SVD performs better than the leading methods for scoring discoveries. We also show the diminishing predictive power of knowledge discovery as we compare our predictions with real associations that appear further into the future. Finally, we examine the strengths and weaknesses of the SVD approach against another well-performing system using several predicted associations.

Availability and implementation

All code and results files for this analysis can be accessed at https://github.com/jakelever/knowledgediscovery.

Supplementary information

Supplementary data are available at Bioinformatics online.
Interface, information, interaction: a narrative review of design and functional requirements for clinical decision support
Authors: Miller Kristen , Mosby Danielle , Capan Muge , Kowalski Rebecca , Ratwani Raj , Noaiseh Yaman , Kraft Rachel , Schwartz Sanford , Weintraub William S , Arnold Ryan
Published: September 2017

Objective

Provider acceptance and associated patient outcomes are widely discussed in the evaluation of clinical decision support systems (CDSSs), but critical design criteria for tools have generally been overlooked. The objective of this work is to inform electronic health record alert optimization and clinical practice workflow by identifying, compiling, and reporting design recommendations for CDSS to support the efficient, effective, and timely delivery of high-quality care.

Material and Methods

A narrative review was conducted from 2000 to 2016 in PubMed and The Journal of Human Factors and Ergonomics Society to identify papers that discussed/recommended design features of CDSSs that are associated with the success of these systems.

Results

Fourteen papers were included as meeting the criteria and were found to have a total of 42 unique recommendations; 11 were classified as interface features, 10 as information features, and 21 as interaction features.

Discussion

Features are defined and described, providing actionable guidance that can be applied to CDSS development and policy. To our knowledge, no reviews have been completed that discuss/recommend design features of CDSS at this scale, and thus we found that this was important for the body of literature. The recommendations identified in this narrative review will help to optimize design, organization, management, presentation, and utilization of information through presentation, content, and function. The designation of 3 categories (interface, information, and interaction) should be further evaluated to determine the critical importance of the categories. Future work will determine how to prioritize them with limited resources for designers and developers in order to maximize the clinical utility of CDSS.

Conclusion

This review will expand the field of knowledge and provide a novel organization structure to identify key recommendations for CDSS.
Nonspecific Symbiosis Between Sophora flavescens and Different Rhizobia
Authors: Liu Yuan Hui , Jiao Yin Shan , Liu Li Xue , Wang Dan , Tian Chang Fu , Wang En Tao , Wang Lei , Chen Wen Xin , Wu Shang Ying , Guo Bao Lin , Guan Zha Gen , Poinsot Véréna , Chen Wen Feng
Published: September 2017

We explored the genetic basis of the promiscuous symbiosis of Sophora flavescens with diverse rhizobia. To determine the impact of Nod factors (NFs) on the symbiosis of S. flavescens, nodulation-related gene mutants of representative rhizobial strains were generated. Strains with mutations in common nodulation genes (nodC, nodM, and nodE) failed to nodulate S. flavescens, indicating that the promiscuous nodulation of this plant is strictly dependent on the basic NF structure. Mutations of the NF decoration genes nodH, nodS, nodZ, and noeI did not affect the nodulation of S. flavescens, but these mutations affected the nitrogen-fixation efficiency of nodules. Wild-type Bradyrhizobium diazoefficiens USDA110 cannot nodulate S. flavescens, but we obtained 14 Tn5 mutants of B. diazoefficiens that nodulated S. flavescens. This suggested that the mutations had disrupted a negative regulator that prevents nodulation of S. flavescens, leading to nonspecific nodulation. For Ensifer fredii CCBAU 45436 mutants, the minimal NF structure was sufficient for nodulation of soybean and S. flavescens. In summary, the mechanism of promiscuous symbiosis of S. flavescens with rhizobia might be related to its nonspecific recognition of NF structures, and the host specificity of rhizobia may also be controlled by currently unknown nodulation-related genes.
Molecular Epidemiology ofPseudomonas syringaepv.syringaeCausing Bacterial Leaf Spot of Watermelon and Squash in Florida
Authors: Newberry E. A. , Babu B. , Roberts P. D. , Dufault N. S. , Goss E. M. , Jones J. B. , Paret M. L.
Published: September 2017

From 2013 to 2014, bacterial leaf spot epidemics incited by Pseudomonas syringae pv. syringae affected an estimated 3,000 ha of watermelon and squash in Florida, and caused foliar blighting and transplant losses in severely affected fields. To investigate the diversity of the causal agent, we isolated 28 P. syringae strains from diseased plants grown in 10 Florida and Georgia counties over the course of 2 years. Strains were confirmed as P. syringae through sequence analysis of the 16S ribosomal RNA, phenotypic, and biochemical profiling; however, 20 displayed an atypical phenotype by exhibiting nonfluorescent activity on King’s medium B agar and being negative for ice-nucleating activity. Multilocus sequence analysis and BOX polymerase chain reaction revealed the presence of two haplotypes among the collected strains that grouped into two distinct clades within P. syringae phylogroup 2. Pathogenicity testing showed that watermelon, cantaloupe, and squash seedlings were susceptible to a majority of these strains. Although both haplotypes were equally virulent on cantaloupe, they differed in virulence on watermelon and squash. The distribution of one haplotype in 9 of 10 Florida and Georgia counties sampled indicated that these epidemics were associated with the recent introduction of a novel clonal P. syringae lineage throughout major watermelon production areas in Florida.
Stimulatory Effects of Flusilazole on Virulence of Sclerotinia sclerotiorum
Authors: Lu Xiaoming , Zhang Ran , Cong Menglong , Li Jianhong , Zhu Fuxing
Published: September 2017

Flusilazole, a member of the demethylation inhibitor fungicides, is highly efficacious for control of Sclerotinia sclerotiorum. To achieve judicious applications of flusilazole, its hormetic effects on virulence of S. sclerotiorum were investigated. Flusilazole sprayed at concentrations from 0.02 to 0.5 μg/ml caused statistically significant (P < 0.05) stimulatory effects on virulence of S. sclerotiorum to potted rapeseed plants, and the maximum stimulation magnitudes were 11.0 and 10.7% for isolates GS-7 and HN-24, respectively. Studies on the time course of the infection process showed that a stimulatory effect on virulence could be discerned at 18 h postinoculation, indicating a direct stimulation mechanism rather than an overcompensation for initial inhibitions. In order to determine whether the stimulations were caused mainly by effects of flusilazole on S. sclerotiorum or on rapeseed plants, mycelia grown on flusilazole-amended potato dextrose agar (PDA) media were inoculated on leaves of rapeseed plants without spraying the fungicide. Mycelium radial growth on PDA supplemented with flusilazole at concentrations from 0.005 to 0.16 μg/ml was inhibited by 10.11 to 48.7% for isolate GS-7 and by 4.1 to 24.9% for isolate HN-24. Observations with a scanning electron microscope showed that flusilazole in PDA at 0.04 and 0.08 μg/ml caused slightly deformed mycelia and twisted mycelial tips. Nevertheless, after inoculating on leaves of potted rapeseed plants, virulence of the inhibited mycelia was statistically significantly (P < 0.05) greater than that of the nontreated control, and the maximum stimulation magnitudes were 16.2 and 19.8% for isolates GS-7 and HN-24, respectively. Studies on a physiological mechanism for virulence stimulations showed that tolerance to hydrogen peroxide did not increase significantly for mycelia grown on flusilazole-amended PDA, thus excluding the possibility of tolerance to reactive oxygen species as a potential mechanism for virulence stimulations.
Control of Citrus Huanglongbing via Trunk Injection of Plant Defense Activators and Antibiotics
Authors: Hu J. , Jiang J. , Wang N.
Published: September 2017

Citrus huanglongbing (HLB) or greening is a devastating disease of citrus worldwide and no effective control measure is currently available. Plant defense activators environmentally friendly compounds capable of inducing resistance against many plant pathogens. Earlier studies showed that foliar spray of plant defense inducers could slow down HLB disease progress. In this study, eight plant defense activators and three antibiotics were evaluated in three field trials for their effect to control HLB by trunk injection of young and mature sweet orange trees. Results showed that four trunk injections of several activators, including salicylic acid, oxalic acid, acibenzolar-S-methyl, and potassium phosphate, provided significant control of HLB by suppressing ‘Candidatus Liberibacter asiaticus’ titer and disease progress. Trunk injection of penicillin, streptomycin, and oxytetracycline hydrochloride resulted in excellent control of HLB. In general, antibiotics were more effective in reduction of ‘Ca. L. asiaticus’ titer and HLB symptom expressions than plant defense activators. These treatments also resulted in increased yield and better fruit quality. Injection of both salicylic acid and acibenzolar-S-methyl led to significant induction of pathogenesis-related (PR) genes PR-1 and PR-2 genes. Meanwhile, injection of either potassium phosphate or oxalic acid resulted in significant induction of PR-2 or PR-15 gene expression, respectively. These results suggested that HLB diseased trees remained inducible for systemic acquired resistance under field conditions. In summary, this study presents information regarding controlling HLB via trunk injection of plant defense activators and antibiotics, which helps citrus growers in decision making regarding developing an effective HLB management program.
Characterization of Putative Effectors from the Cereal Cyst Nematode Heterodera avenae
Authors: Cui Jiang-Kuan , Peng Huan , Qiao Fen , Wang Gao-Feng , Huang Wen-Kun , Wu Du-Qing , Peng Deliang
Published: September 2017

Few molecular details of effectors of Heterodera avenae parasitism are known. We performed a high-throughput sequencing analysis of the H. avenae transcriptome at five developmental stages. A total of 82,549 unigenes were ultimately obtained, and 747 transcripts showed best hits to genes putatively encoding carbohydrate-active enzymes in plant-parasitic nematodes that play an important role in the invasion process. A total of 1,480 unigenes were homologous to known phytonematode effectors, and 63 putative novel effectors were identified in the H. avenae transcriptomes. Twenty-three unigenes were analyzed by qRT-PCR and confirmed to be highly expressed during at least one developmental stage. For in situ hybridization, 17 of the 22 tested putative effectors were specifically expressed and located in the subventral gland cells, and five putative novel effectors were specifically expressed in the dorsal gland. Furthermore, 115 transcripts were found to have putative lethal RNA interference (RNAi) phenotypes. Three target genes with lethal RNAi phenotypes and two of the four tested putative effectors were associated with a decrease in the number of cysts through in vitro RNAi technology. These transcriptomic data lay a foundation for further studies of interactions of H. avenae with cereal and H. avenae parasitic control.
Fine Mapping of the Dominant Potyvirus Resistance Gene Pvr7 Reveals a Relationship with Pvr4 in Capsicum annuum
Authors: Venkatesh Jelli , An Jeongtak , Kang Won-Hee , Jahn Molly , Kang Byoung-Cheorl
Published: September 2017

Pepper mottle virus (PepMoV) is the most common potyvirus infection of pepper plants and causes significant yield losses. The Pvr7 gene from Capsicum chinense PI159236 and the Pvr4 gene from C. annuum CM334 both have been reported to confer dominant resistance to PepMoV. The Pvr7 locus conferring resistance to PepMoV in C. annuum ‘9093’ was previously mapped to chromosome 10. To develop a high-resolution map of the Pvr7 locus in 9093, we constructed an intraspecific F2 mapping population consisting of 916 individuals by crossing PepMoV-resistant C. annuum ‘9093’ and the PepMoV-susceptible C. annuum ‘Jeju’. To delimit the Pvr7 target region, single-nucleotide polymorphism (SNP) markers derived from the Pvr4 region were used for genotyping the F2 population. Molecular mapping delimited the Pvr7 locus to a physical interval of 258 kb, which was the same region as Pvr4 on chromosome 10. Three SNP markers derived from Pvr4 mapping perfectly cosegregated with PepMoV resistance. Sequencing analyses of the Pvr7 flanking markers and the Pvr4-specific gene indicated that Pvr7 and Pvr4 are the same gene. Resistance spectrum analysis of 9093 against pepper potyviruses showed that 9093 has a resistance spectrum similar to that of cultivar CM334. These combined results demonstrate that, unlike previously thought, the dominant PepMoV resistance in 9093 could be derived from C. annuum ‘CM334’, and that Pvr4 and Pvr7 should be considered as the same locus.
Size Matters: Defining Critical in Bone Defect Size!
Authors: Schemitsch Emil H.
Published: September 2017

Bone defects are common and are associated with a significant burden of disease. The treatment of these injuries remains controversial, particularly those defects which are critical sized. Despite the need for decision making to be evidence based, a lack of consensus around definitions of critical-sized defects still exists, particularly around those defects in the 1–3 cm range. There is a need to define “critical” in bone defect size because noncritical defects may heal without planned reconstruction and secondary surgery. This article reviews the current evidence around the definition of a critical-sized bone defect and concludes that defects in the order of 2.5 cm or greater seem to have a poor natural history.
Segmental Bone Loss Reconstruction Using Ring Fixation
Authors: Quinnan Stephen M.
Published: September 2017

Ring fixation is a powerful tool in the treatment of bone defects. The ability to create high-quality, biologically normal new bone of even massive proportions using distraction osteogenesis is a major reason for its success. In addition, ring fixation provides the ability to limit the risk of deep infection, improves flexibility in limb length control and alignment, and increases soft tissue coverage options. The drawbacks of ring fixation include long frame times, pin problems, risk of joint contractures, and difficult usage in areas with a large soft tissue envelope such as the thigh. Significant advancements such as hydroxyapatite coated pins, internal cable transport, multifocal transport, and combined techniques with internal fixation have helped increase the effectiveness of ring fixator use by minimizing many of the drawbacks. At present, ring fixation provides the most effective means of treatment for large bone defects in many clinic situations.
Comparison Between Viscous Teardrops and Saline Solution to Fill Orthokeratology Contact Lenses Before Overnight Wear
Authors: Carracedo Gonzalo , Villa-Collar Cesar , Martin-Gil Alba , Serramito Maria , Santamaría Leticia
Published: September 2017

Objective:

To compare, in terms of efficacy, the differences between the use of saline solution and a viscous artificial tear to fill the lens during the first month of orthokeratology wear.

Methods:

A pilot, double-masked, crossed, randomized, and prospective study was conducted. In this study, 20 subjects (14 males and 6 females) with a mean age of 16.29±6.22 years (range, 10–26) were fitted with orthokeratology contact lenses. For the study, nonpreserved 0.9% NaCl commercial saline solution (Avizor, Madrid, Spain) and nonpreserved artificial teardrops with 0.3% of hyaluronic acid (Ocudry 0.3%; Avizor, Madrid, Spain) were used. Corneal staining, tear break up time (TBUT), topography, refraction, visual acuity, and subjective comfort and vision with the visual analog scale (score from 0 to 10, being 10 better comfort and vision) were evaluated at 1 day, 1 week, and 1 month of contact lens wear.

Results:

The corneal staining was statistically greater in the saline group than in the Ocudry group for the first day and during 1 week of wear (P<0.05). Comfort was found to be statistically better, with Ocudry 0.3% than saline solution, being 7.17±1.94 and 6.37±1.63, for the first day, and 8.78±0.43 and 8.15±0.62 for the day 28, respectively (P<0.05). However, no differences were found for subjective vision scores, TBUT, spherical equivalent, best-corrected visual acuity and uncorrected visual acuity, and mean keratometry between groups for any visit (P>0.05).

Conclusion:

Viscous artificial tears improve the subjective comfort of patients and reduce the corneal staining, compared with saline solution during the orthokeratology lenses fitting process. However, no differences between solutions for the treatment efficacy, in vision and corneal topography, were found.
A Theory-Based and Culturally Aligned Training Program on Breast and Cervical Cancer Prevention for South Asian Community Health Workers
Authors: So Winnie K.W. , Kwong Alice N.L. , Chen Joanne M.T. , Chan Joanne C.Y. , Law Bernard M.H. , Sit Janet W.H. , Chan Carmen W.H.
Published: September 2017

Background

Cancer screening uptake among South Asian ethnic minorities is reported to be relatively low. An outreach program, led by community health workers (CHWs), may increase the minority group’s awareness of the importance of cancer screening.

Objective

The aim of this study was to assess the feasibility and effectiveness of a theory-based, culturally sensitive program to train South Asian women in Hong Kong as CHWs.

Methods

A CHW training program, guided by the Empowerment Model and the Health Belief Model, was developed and implemented. Its feasibility was evaluated through the recruitment of South Asian women to the program and their satisfaction with it. Its effectiveness was assessed by a test of knowledge, the participants’ self-efficacy and competence, and their readiness to work as CHWs.

Results

Five South Asian women were recruited to the training program. Outcomes included increased participants’ knowledge of cancer and improved self-efficacy and competence in working as CHWs. All participants were highly satisfied with the program, although the addition of practical sessions in the South Asian community was suggested as a further improvement.

Conclusion

It seems to be feasible to train South Asian CHWs to deliver interventions to promote their peers’ awareness of breast and cervical cancer prevention, although challenges exist in recruitment of trainees. More hands-on practical opportunities as CHWs would likely increase their effectiveness.

Implications for Practice

The theoretical framework of our CHW training program and the incorporated cultural components could be useful for the development of future programs for training South Asian CHWs in delivering interventions on cancer prevention.
Single Cell RNA Sequencing of stem cell-derived retinal ganglion cells
Authors: Daniszewski Maciej , Senabouth Anne , Nguyen Quan , Crombie Duncan E. , Lukowski Samuel W. , Kulkarni Tejal , Zack Donald J , Pébay Alice , Powell Joseph E. , Hewitt Alex W.
Published: September 2017

We used human embryonic stem cell-derived retinal ganglion cells (RGCs) to characterize the transcriptome of 1,174 cells at the single cell level. The human embryonic stem cell line BRN3B-mCherry A81-H7 was differentiated to RGCs using a guided differentiation approach. Cells were harvested at day 36 and subsequently prepared for single cell RNA sequencing. Our data indicates the presence of three distinct subpopulations of cells, with various degrees of maturity. One cluster of 288 cells upregulated genes involved in axon guidance together with semaphorin interactions, cell-extracellular matrix interactions and ECM proteoglycans, suggestive of a more mature phenotype.
Natural selection on plasticity of thermal traits in a highly seasonal environment
Authors: Bacigalupe Leonardo D. , Gaitan-Espitia Juan D. , Barria Aura M. , Gonzalez-Mendez Avia , Ruiz-Aravena Manuel , Trinder Mark , Sinervo Barry
Published: September 2017

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100048). For ectothermic species with broad geographical distributions, latitudinal/altitudinal variation in environmental temperatures (averages and extremes) are expected to shape the evolution of physiological tolerances and the acclimation capacity (i.e., degree of phenotypic plasticity) of natural populations. This can create geographical gradients of selection in which environments with greater thermal variability (e.g., seasonality) tend to favour individuals that maximize performance across a broader range of temperatures compared to more stable environments. Although thermal acclimation capacity plays a fundamental role in this context, it is unknown whether natural selection targets this trait in natural populations. Here we addressed such an important gap in our knowledge by measuring survival, through mark recapture integrated into an information-theoretic approach, as a function of the plasticity of critical thermal limits for activity, behavioural thermal preference and the thermal sensitivity of metabolism in the northernmost population of the four-eyed frogPleurodema thaul. Overall, our results indicate that thermal acclimation in this population is not being targeted by directional selection, although there might be signals of selection on individual traits. According to the most supported models, survival decreased in individuals with less tolerance to cold when cold-acclimated (probably because daily low extremes are frequent during the cooler periods of the year) and increased with body size. However, in both cases, the directional selection estimates were non-significant.
PiFlow: A Biocompatible Low-Cost Programmable Dynamic Flow Pumping System Utilizing a Raspberry Pi Zero and Commercial Piezoelectric Pumps
Authors: Kassis Timothy , Perez Paola M. , Yang Chloe J. W. , Soenksen Luis R. , Trumper David L. , Griffith Linda G.
Published: September 2017

With the rise of research utilizing microphysiological systems (MPSs), the need for tools that enable the physiological mimicking of the relevant cellular environment is vital. The limited ability to reproduce crucial features of the microenvironment, such as surrounding fluid flow and dynamic changes in biochemical stimuli, severely limits the types of experiments that can be carried out. Current equipment to achieve this, such as syringe and peristaltic pumps, is expensive, large, difficult to program and has limited potential for scalability. Here, we present a new pumping platform that is open-source, low-cost, modular, scalable, fully-programmable and easy to assemble that can be incorporated into cell culture systems to better recapitulate physiological environments. By controlling two commercially available piezoelectric pumps using a Raspberry Pi Zero microcontroller, the system is capable of producing arbitrary dynamic flow profiles with reliable flow rates ranging from 1 to 3,000 µL/min as specified by an easily programmable Python-based script. We validated the accuracy of the flow rates, the use of time-varying profiles, and the practicality of the system by creating repeatable dynamic concentration profiles using a 3D-printed static micromixer.
Auditory brainstem responses to continuous natural speech in human listeners
Authors: Maddox Ross K , Lee Adrian KC
Published: September 2017

Speech is an ecologically essential signal whose processing begins in the subcortical nuclei of the auditory brainstem, but there are few experimental options for studying these early responses under natural conditions. While encoding of continuous natural speech has been successfully probed in the cortex with neurophysiological tools such as electro- and magnetoencephalography, the rapidity of subcortical response components combined with unfavorable signal to noise ratios has prevented application of those methods to the brainstem. Instead, experiments have used thousands of repetitions of simple stimuli such as clicks, tonebursts, or brief spoken syllables, with deviations from those paradigms leading to ambiguity in the neural origins of measured responses. In this study we developed and tested a new way to measure the auditory brainstem response to ongoing, naturally uttered speech. We found a high degree of morphological similarity between the speech-evoked auditory brainstem responses (ABR) and the standard click-evoked ABR, notably a preserved wave V, the most prominent voltage peak in the standard click-evoked ABR. Because this method yields distinct peaks at latencies too short to originate from the cortex, the responses measured can be unambiguously determined to be subcortical in origin. The use of naturally uttered speech to evoke the ABR allows the design of engaging behavioral tasks, facilitating new investigations of the effects of cognitive processes like language processing and attention on brainstem processing.

SIGNIFICANCE STATEMENT

Speech processing is usually studied in the cortex, but it starts in the auditory brainstem. However, a paradigm for studying brainstem processing of continuous natural speech in human listeners has been elusive due to practical limitations. Here we adapt methods that have been employed for studying cortical activity to the auditory brainstem. We measure the response to continuous natural speech and show that it is highly similar to the click-evoked response. The method also allows simultaneous investigation of cortical activity with no added recording time. This discovery paves the way for studies of speech processing in the human brainstem, including its interactions with higher order cognitive processes originating in the cortex.
Interaction Between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer
Authors: Yuan Ce , Burns Michael , Subramanian Subbaya , Blekhman Ran
Published: September 2017

Background

Although variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNAs expression in human CRC tumor and normal tissues and the microbiome composition associated with these same tissues.

Method

We sequenced the small RNAs from patient-matched tumor and normal tissue samples collected from 44 human CRC patients performed an integrated analysis with microbiome taxonomic composition data from these same samples. We then interrogated the functions of the bacteria correlated with miRNAs that were differentially expressed (DE) between tumor and matched normal tissues, as well as the functions of miRNAs correlated with bacterial taxa that have been previously associated with CRC, including Fusobacterium, Providencia, Bacteroides, Akkermansia, Roseburia, Porphyromonas, and Peptostreptococcus.

Results

We identified 76 miRNAs as DE between CRC and normal tissue, including known oncogenic miRNAs miR-182, miR-503, and miR-17∼92. These DE miRNAs were correlated with the relative abundance of several bacterial taxa, including Firmicutes, Bacteroidetes, and Proteobacteria. Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions, and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa.

Conclusions

Our work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. Our results support a role for miRNAs in mediating a bi-directional host-microbiome interaction in CRC. In addition, we highlight sets of potentially interacting microbes and host miRNAs, suggesting several pathways that can be targeted via future therapies.
Bcl11b is a Newly Identified Regulator of Vascular Smooth Muscle Phenotype and Arterial Stiffness
Authors: Valisno Jeff Arni C. , Elavalakanar Pavania , Nicholson Christopher , Singh Kuldeep , Avram Dorina , Cohen Richard A. , Mitchell Gary F. , Morgan Kathleen G. , Seta Francesca
Published: September 2017

B-cell leukemia 11b (Bcl11b) is a zinc-finger transcription factor known as master regulator of T lymphocytes and neuronal development during embryogenesis. Bcl11b-interacting protein COUP-TFII is required for atrial development and vasculogenesis, however a role of Bcl11b in the adult cardiovascular system is unknown. A genome-wide association study (GWAS) recently showed that a gene desert region downstream ofBCL11Band known to function asBCL11Benhancer harbors single nucleotide polymorphisms (SNPs) associated with increased arterial stiffness. Based on these human findings, we sought to examine relations between Bcl11b and arterial function using mice with Bcl11b deletion. We report for the first time that Bcl11b is expressed in vascular smooth muscle (VSM) and transcriptionally regulates the expression of VSM contractile proteins smooth muscle myosin and smooth muscle α-actin. Lack of Bcl11b in VSM-specific Bcl11b null mice (BSMKO) resulted in increased expression of Ca++-calmodulin-dependent serine/threonine phosphatase calcineurin in BSMKO VSM cells, cultured in serum-free condition, and in BSMKO aortas, which showed an inverse correlation with levels of phosphorylated VASPS239, a regulator of cytoskeletal actin rearrangements. Moreover, decreased pVASPS239in BSMKO aortas was associated with increased actin polymerization (F/G actin ratio). Functionally, aortic force, stress and wall tension, measured ex vivo in organ baths, were increased in BSMKO aortas and BSMKO mice had increased pulse wave velocity, thein vivoindex of arterial stiffness, compared to WT littermates. Despite having no effect on baseline blood pressure or angiotensin II-induced hypertension, Bcl11b deletion in VSM increased the incidence of aortic aneurysms in BSMKO mice. Aneurysmal aortas from angII-treated BSMKO mice had increased number of apoptotic VSM cells. In conclusion, we identified VSM Bcl11b as a novel and crucial regulator of VSM cell phenotype and vascular structural and functional integrity.
2D:4D and spatial abilities: From rats to humans
Authors: Müller N , Campbell S , Nonaka M , Rost TM , Pipa G , Konrad BN , Steiger A , Czisch M , Fernández G , Dresler M , Genzel L
Published: September 2017

Variance in spatial abilities are thought to be determined by in utero levels of testosterone and oestrogen, measurable in adults by the length ratio of the 2ndand 4thdigit (2D:4D). We confirmed the relationship between 2D:4D and spatial performance using rats in two different tasks (paired-associate task and watermaze) and replicated this in humans. We further clarified anatomical and functional brain correlates of the association between 2D:4D and spatial performance in humans.
Efficient multi-task chemogenomics for drug specificity prediction
Authors: Playe Benoit , Azencott Chloé-Agathe , Stoven Véronique
Published: September 2017

Adverse drug reactions, also called side effects, range from mild to fatal clinical events and significantly affect the quality of care. Among other causes, side effects occur when drugs bind to proteins other than their intended target. As experimentally testing drug specificity against the entire proteome is out of reach, we investigate the application of chemogenomics approaches. We formulate the study of drug specificity as a problem of predicting interactions between drugs and proteins at the proteome scale. We build several benchmark datasets, and proposeNN-MT, a multi-task Support Vector Machine (SVM) algorithm that is trained on a limited number of data points, in order to solve the computational issues or proteome-wide SVM for chemogenomics. We compareNN-MTto different state-of-the-art methods, and show that its prediction performances are similar or better, at an efficient calculation cost. Compared to its competitors, the proposed method is particularly efficient to predict (protein, ligand) interactions in the difficult double-orphan case, i.e. when no interactions are previously known for the protein nor for the ligand. TheNN-MTalgorithm appears to be a good default method providing state-of-the-art or better performances, in a wide range of prediction scenarii that are considered in the present study: proteome-wide prediction, protein family prediction, test (protein, ligand) pairs dissimilar to pairs in the train set, and orphan cases.
Histone H3K4 methylation-dependent and -independent functions of Set1A/COMPASS in embryonic stem cell self-renewal and differentiation
Authors: Sze Christie C. , Cao Kaixiang , Collings Clayton K. , Marshall Stacy A. , Rendleman Emily J. , Ozark Patrick A. , Chen Fei Xavier , Morgan Marc A. , Wang Lu , Shilatifard Ali
Published: September 2017

Of the six members of the COMPASS (complex of proteins associated with Set1) family of histone H3 Lys4 (H3K4) methyltransferases identified in mammals, Set1A has been shown to be essential for early embryonic development and the maintenance of embryonic stem cell (ESC) self-renewal. Like its familial relatives, Set1A possesses a catalytic SET domain responsible for histone H3K4 methylation. Whether H3K4 methylation by Set1A/COMPASS is required for ESC maintenance and during differentiation has not yet been addressed. Here, we generated ESCs harboring the deletion of the SET domain of Set1A (Set1AΔSET); surprisingly, the Set1A SET domain is dispensable for ESC proliferation and self-renewal. The removal of the Set1A SET domain does not diminish bulk H3K4 methylation in ESCs; instead, only a subset of genomic loci exhibited reduction in H3K4me3 in Set1AΔSET cells, suggesting a role for Set1A independent of its catalytic domain in ESC self-renewal. However, Set1AΔSET ESCs are unable to undergo normal differentiation, indicating the importance of Set1A-dependent H3K4 methylation during differentiation. Our data also indicate that during differentiation, Set1A but not Mll2 functions as the H3K4 methylase on bivalent genes and is required for their expression, supporting a model for transcriptional switch between Mll2 and Set1A during the self-renewing-to-differentiation transition. Together, our study implicates a critical role for Set1A catalytic methyltransferase activity in regulating ESC differentiation but not self-renewal and suggests the existence of context-specific H3K4 methylation that regulates transcriptional outputs during ESC pluripotency.
Lymphangiogenesis guidance by paracrine and pericellular factors
Authors: Vaahtomeri Kari , Karaman Sinem , Mäkinen Taija , Alitalo Kari
Published: September 2017

Lymphatic vessels are important for tissue fluid homeostasis, lipid absorption, and immune cell trafficking and are involved in the pathogenesis of several human diseases. The mechanisms by which the lymphatic vasculature network is formed, remodeled, and adapted to physiological and pathological challenges are controlled by an intricate balance of growth factor and biomechanical cues. These transduce signals for the readjustment of gene expression and lymphatic endothelial migration, proliferation, and differentiation. In this review, we describe several of these cues and how they are integrated for the generation of functional lymphatic vessel networks.
Improved crystal structure solution from powder diffraction data by the use of conformational information
Authors: Kabova Elena A. , Cole Jason C. , Korb Oliver , Williams Adrian C. , Shankland Kenneth
Published: September 2017

The effect of introducing conformational information to theDASHimplementation of crystal structure determination from powder diffraction data is investigated using 51 crystal structures, with the aim of allowing increasingly complex crystal structures to be solved more easily. The findings confirm that conformational information derived from the Cambridge Structural Database is indeed of value, considerably increasing the chances of obtaining a successful structure determination. Its routine use is therefore encouraged.
How platforms are transforming customer information management
Authors: Stone Merlin , Aravopoulou Eleni , Gerardi Gherardo , Todeva Emanuela , Weinzierl Luisa , Laughlin Paul , Stott Ryan
Published: September 2017

Purpose

The purpose of this paper is to explain how ecosystems and platforms have evolved to manage customer information and to identify the management, research and teaching implications of this evolution.

Design/methodology/approach

This paper is based on research and industrial experience of two of the co-authors in customer relationship management, further developed with other co-authors in the field of business models, the research and teaching experience of the university authors and cross-functional literature reviews in the areas of strategy, marketing, economics, organizational behaviour and information management.

Findings

This paper shows that digitalization, cloud computing and new information-based platforms are beginning to change how customer information is being managed, creating new opportunities for improving marketing, customer relationship management and business strategy.

Research limitations/implications

The impact of platforms on the management of customer information needs to be confirmed by primary empirical research.

Practical implications

This paper identifies the need for senior marketing management to examine closely how internal and external/public customer information platforms may enhance their capability for managing customers and setting new strategic directions.

Social implications

The emergence of giant multi-sided platforms has clear implications for data protection and privacy, which need to be explored more in research.

Originality/value

This paper highlights the move to customer information platforms and identifies how senior managers should consider them as an option for better customer information management and as a basis for new business strategies.
Measuring the impact of relational capital on customer performance in the SME B2B sector
Authors: Agostini Lara , Nosella Anna , Soranzo Benedetta
Published: September 2017

Purpose

The purpose of this paper is to investigate the influence that different components of relational capital (marketing capability, open innovation with business and scientific partners, technological reputation, brand) have on customer performance (CP). Moreover, the moderating effect of absorptive capacity on such relationships is tested.

Design/methodology/approach

First, the direct relationship between the different components of relational capital and CP is analyzed through a linear regression model. Then, to test the moderating effect, two distinct regression analyses are conducted into two sub-samples, defined according to the level of absorptive capacity. The authors carried out these analyses on a sample of 150 small- and medium-sized enterprises (SMEs) in the medium- and high-tech B2B context.

Findings

Results of this study prove that CP is enhanced through firm marketing capability, open innovation with business partners and technological reputation, while brand and open innovation with scientific partner do not have an association with CP. In particular, the impact of marketing capability and open innovation with business actors on CP is greater for firms with higher absorptive capacity.

Research limitations/implications

This paper, highlighting the relevance of relational capital and absorptive capacity in improving CP, enhances our knowledge about the factors that help to strengthen the relationships with customers, which is an under-investigated issue especially for SMEs competing in B2B industries, and extends our knowledge on open innovation practices.

Practical implications

Findings of this paper suggest that, to achieve better CP, managers should pay special attention to nurturing their marketing capability and high-quality relationships with external actors and invest in absorptive capacity to enhance the positive effect of such linkages.

Originality/value

This work, combining the external perspective of relational capital and the internal organizational dimension of absorptive capacity, provides valuable insights about the knowledge and resource mix that firms might rely on to achieve better customer satisfaction and loyalty.
Assessment of turbulence models for transonic oscillating airfoil
Authors: Tahani Mojtaba , Masdari Mehran , Eivazi Hamidreza , Tatar Massoud
Published: September 2017

Purpose

This paper aims to investigate numerical solution of transonic flow around NACA0012 airfoil under sinusoidal pitch oscillation. Accordingly, effects of the amplitude and frequency of oscillations on aerodynamic coefficients are evaluated and the efficiency of the turbulent models, K-ω shear-stress transport (SST), scale adaptive simulation (SAS) and delayed detached eddy simulation (DDES), in simulation of the nonlinear phenomena – i.e. the interaction between shock and boundary layer and the shock oscillations – is studied.

Design/methodology/approach

K-ω SST, SAS and DDES models are used as turbulence approaches. The numerical results are compared with available experimental and numerical information.

Findings

According to the results inside the buffet boundaries, the DDES turbulent model expresses results that are more appropriate; however, SAS and SST models are not efficient enough in evaluating the characteristics of nonlinear flow.

Originality/value

In this research study, hybrid RANS-LES turbulence model is engaged to simulate transonic flow around pitching NACA0012 airfoil, and results are compared to the SAS and Reynolds Average Navier–Stocks simulations as well as available numerical and experimental data. In addition, effects of the amplitude and frequency of oscillations on aerodynamic coefficients are evaluated in buffet regions.