bluuebunny/crossref_metadata_2025 huggingface dataset:
Gain characteristics of InGaN quantum wells with AlGaInN barriers
Authors: Fu Hanlin , Sun Wei , Ogidi-Ekoko Onoriode , Goodrich Justin C. , Tansu Nelson
Published: April 2019

A reduction of the threshold current density of InGaN quantum well (QW) lasers is found from the usage of AlGaInN barriers. Large bandgap and strain-managing AlGaInN barriers surrounding the InGaN quantum wells’ (QWs) active regions are investigated via the 6-band self-consistent k·p formalism for their spontaneous emission, material gain, and threshold current density properties. In this study, quaternary AlGaInN alloys both lattice-matched and tensile-strained to GaN, with bandgaps ranging from 3.4 eV to 5.2 eV, are employed as thin barriers (∼1 nm) surrounding the InGaN active region. The AlGaInN barriers provide strong carrier confinement, which improves the electron and hole wavefunction overlap by ∼25%, while simultaneously reducing the strain relaxation in the active region. This study shows that InGaN QWs surrounded by AlGaInN barriers improve the material gain by ∼30%, reduce the threshold carrier density by ∼18%, and reduce the threshold current density by ∼40% over the conventional InGaN/GaN QW structure. Our results indicate that the AlGaInN barriers substantially enhance the radiative efficiency and reduce the power consumption for light emitting diodes (LEDs) and laser diodes (LDs), making them very attractive candidates for the design of low threshold optoelectronic devices.
Recent advances in high refractive index dielectric nanoantennas: Basics and applications
Authors: Barreda A. I. , Saiz J. M. , González F. , Moreno F. , Albella P.
Published: April 2019

Nanoparticles made of High Refractive Index dielectric materials have been proposed as an alternative to metals driven by their low-losses and magnetic response. The coherent effects between the electric and magnetic resonances are responsible for their exceptional directionality properties that make them attractive in applications where enhancing light-matter interaction and controlling the radiation direction is extremely relevant. These nanoparticles, when used as unit-cells of more complex systems, such as metasurfaces, result to be essential in the design of novel optical devices. Their low-losses, strong confinement of electromagnetic energy and the outstanding scattering efficiencies show these nanoantennas as promising candidates for Surface Enhanced Spectroscopies, non-linear phenomena or sensing. Here, we describe and discuss the origins and recent advances in this rapidly developing field of dielectric nanophotonics, paying special attention to the main significant contributions we have done since its startup to boost its progress. In particular, light directivity, steering and switching of light, spectroscopy, sensing and non-linear phenomena, third harmonic generation are some of the applications that motivated this brief overview.
Channel length scaling of over 100% biaxially stretchable carbon nanotube transistors
Authors: Wu Meng-Yin , Wang Jialiang , Arnold Michael S.
Published: April 2019

Deformable field effect transistors (FETs) are needed for future technologies such as stretchable electronics. We have previously integrated buckled networks of polymer-sorted semiconducting carbon nanotubes and buckled layers of an ion gel dielectric onto elastomeric substrates to create FETs with a channel length of 100 μm that are biaxially stretchable. However, the channel length scaling behavior of this type of FET has not yet been investigated. Of particular concern is the viability of this device architecture when the channel length is reduced below 10 μm, approaching the characteristic buckling length-scale. Here, we fabricate and test buckled nanotube FETs with channel lengths of 8, 17, and 31 μm. We find that the buckling length-scale decreases as the channel length is reduced and that devices at all channel lengths are viable, demonstrating a field-effect mobility of >5 cm2 V−1 s−1 and an on/off ratio of >104, with stability up to 100% biaxial elongation without degradation of performance. A biaxially stretchable inverter is also demonstrated. These findings are important because smaller and higher conductivity FETs that are deformable are needed for next-generation technologies such as stretchable, high-resolution displays and sensors.
Free-energy analysis of the hydration and cosolvent effects on the β-sheet aggregation through all-atom molecular dynamics simulation
Authors: Masutani Keiichi , Yamamori Yu , Kim Kang , Matubayasi Nobuyuki
Published: April 2019

Energetics was analyzed for the aggregation of an 11-residue peptide. An all-atom molecular dynamics simulation was conducted with explicit solvent, and the energy-representation theory of solution was employed to compute the solvation free energies of the peptide and its aggregates. The aggregation in the pure-water solvent was observed to be inhibited by the solvation. The driving force of aggregate formation is the interactions among the peptide molecules, and the sum of the intra-aggregate and solvation terms per monomer is more favorable for larger aggregates. The effect of the cosolvent was then examined by focusing on the mixtures of water with urea and dimethyl sulfoxide (DMSO). It was actually shown that the derivative of the excess chemical potential of a flexible solute species with respect to the cosolvent concentration is determined exactly by the corresponding derivative of the free energy of solvation. The cosolvent effect on the equilibrium of aggregate formation can thus be addressed by comparing the solvation free energies with and without the cosolvent, and both the urea and DMSO cosolvents were found to inhibit the aggregation. The cosolvent-induced change in the solvation free energy was further decomposed into the contributions from the cosolvent and water. Their dependencies on the degree of aggregation were seen to be weak for large aggregates, and the roles of the electrostatic, van der Waals, and excluded-volume components in the solvation energetics were discussed.
Spiral waves in externally excited neuronal network: Solvable model with a monotonically differentiable magnetic flux
Authors: Rajagopal Karthikeyan , Parastesh Fatemeh , Azarnoush Hamed , Hatef Boshra , Jafari Sajad , Berec Vesna
Published: April 2019

Spiral waves are particular spatiotemporal patterns connected to specific phase singularities representing topological wave dislocations or nodes of zero amplitude, witnessed in a wide range of complex systems such as neuronal networks. The appearance of these waves is linked to the network structure as well as the diffusion dynamics of its blocks. We report a novel form of the Hindmarsh–Rose neuron model utilized as a square neuronal network, showing the remarkable multistructure of dynamical patterns ranging from characteristic spiral wave domains of spatiotemporal phase coherence to regions of hyperchaos. The proposed model comprises a hyperbolic memductance function as the monotone differentiable magnetic flux. Hindmarsh–Rose neurons with an external electromagnetic excitation are considered in three different cases: no excitation, periodic excitation, and quasiperiodic excitation. We performed an extensive study of the neuronal dynamics including calculation of equilibrium points, bifurcation analysis, and Lyapunov spectrum. We have found the property of antimonotonicity in bifurcation scenarios with no excitation or periodic excitation and identified wide regions of hyperchaos in the case of quasiperiodic excitation. Furthermore, the formation and elimination of the spiral waves in each case of external excitation with respect to stimuli parameters are investigated. We have identified novel forms of Hindmarsh–Rose bursting dynamics. Our findings reveal multipartite spiral wave formations and symmetry breaking spatiotemporal dynamics of the neuronal model that may find broad practical applications.
Molecular insights into ionic liquid/aqueous interface of phosphonium based phase-separable ionic liquids
Authors: Venkatesan Shanmuga S. , Huda Md. Masrul , Rai Neeraj
Published: April 2019

Phosphonium based phase-separable ionic liquids (PSILs) are promising green solvents for dissolution of cellulose and lignin, a necessary step for conversion of biomass to fuels and chemicals. The knowledge of interfacial behavior of ionic liquid/solvent systems is critical for designing efficient separation processes. Here, molecular dynamics simulations are carried out for aqueous interface of tetraalkylphosphonium ionic liquids with chloride and acetate as anions to investigate IL miscibility with water. The transition zone from miscible to immiscible behavior was observed for alkyl chain lengths of 6 to 8. Emulsion phase was observed for [P8888]+ ion and multiple IL/water interface was observed for [P12121212]+ phosphonium cation. IL/water interface is observed to be enriched with solvated anions with phosphorous atom oriented towards the aqueous phase. The potential of mean force calculations suggest that as the alkyl chain of the phosphonium cations increase, so does the driving force for aggregation of cations in the aqueous phase. Due to the difference in the molecular shape and size, anions are better solvated by the water molecules, and these ions diffuse into the aqueous phase. Furthermore, the analysis of selected pair interactions provides insights into the nature of intermolecular forces and the role of the alkyl side chains on the interfacial properties.
A novel TM01-TE01 high-power microwave mode converter
Authors: Gong Hongzhou , Yuan Chengwei , Zhao Xuelong , Zhang Qiang
Published: April 2019

This study presents the design and simulation of a novel type of TM01-TE01 mode converter for high-power microwave applications, which efficiently converts the TM01 circular waveguide mode into the TE01 circular waveguide mode. The converter is composed of three sections: power-dividing section, twist-waveguide section and power-combining section. These sections were analyzed and discussed respectively, and the whole converter structure was studied numerically. The results show that at the central frequency 12.5 GHz, the TM01-TE01 conversion loss of the converter made of aluminum is 0.05 dB and the bandwidth for S21 > 0.25 dB is 2.73 GHz. Moreover, the power-handling capacity is over 2 GW.
Effectiveness of a dynamic usage based computer assisted language program
Authors: Irshad Mufeeda , Keijzer Merel , Wieling Martijn , Verspoor Marjolijn
Published: April 2019

The current paper explores whether a Dynamic Usage Based (DUB) approach – which takes authentic meaningful
language use with repetition and scaffolding for comprehension as its basis – can also be implemented in a CALL environment. The
effectiveness of the DUB-CALL program was tested in a semester-long experiment, comparing it with a teacher-fronted DUB program
(using the same materials as the CALL program) and a traditional CLT program; 228 university undergraduates in Sri Lanka
participated. Language gains were assessed in a pre-post design with an objective General English Proficiency (GEP) test and a
writing task. The results show that the students in the DUB-CALL condition performed significantly better on the GEP test than the
students in the two teacher-fronted classes. The results of the writing tests show that all groups improved significantly, but
here there were no differences among groups.
Eighth graders’ expository text comprehension
Authors: Welie Camille , Schoonen Rob , Kuiken Folkert
Published: April 2019

The present study examined whether ten motivations to read
expository texts moderated the effects of cognitive skills on eighth graders’
expository text comprehension, while accounting for the main effects of
cognitive skills. Furthermore, it was examined whether the effect of
motivational dimensions on expository text comprehension differed between
monolingual and bilingual Dutch students, and between poor and good readers.
Hundred fifty-two eighth graders took tests measuring their expository text
comprehension, sentence reading fluency, linguistic knowledge, metacognitive
knowledge and motivations to read expository texts. None of ten motivational
aspects did moderate the effect of cognitive skills on expository text
comprehension. Furthermore, there were no differences between monolingual and
bilingual Dutch students, or between poor and good readers, in terms of the
relationship between motivational dimensions and expository text comprehension.
Differences between our findings and results from other studies are interpreted
in the context of measurement specificity and the school system.
The limitations of accommodation: the changing legal context of religion at work in the United States
Authors: Phipps
Published: April 2019

Other authors have warned that the legal standard of accommodation is insufficient as a strategy for practicing managers leading religiously and spiritually diverse workforces. Recent changes in the legal context of faith at work have only amplified those concerns. This article examines
the adoption of state laws known as Religious Freedom Restoration Acts, or RFRA’s, as well as the US Supreme Court ruling in Burwell v. Hobby Lobby. Both of these changes exacerbate the concerns previously articulated, and illustrate the limitations of using the legal standard of
accommodation as a management strategy for negotiating diverse religious and spiritual expression in the workplace. The nature of these two developments is explained, together with a discussion of their significance for practitioners and researchers in the field of management, spirituality,
and religion (MSR).
Learning is what you do for yourself: What I learned as a student and then as a co-teacher with professor André Delbecq
Authors: Merchant Nilofer
Published: April 2019

I was working full-time while grinding slowly through Santa Clara’s night-school MBA program when I took Andre Delbecq’s course in Spirituality of Organizational Leadership. By this point in my career, I had run the North America operations of Autodesk, a $200M business
and had launched the first web server and the first web authoring software. But I had also been fired from two major jobs and was struggling with what defined “success”. Our communication continued beyond the immediate course and even beyond graduation. Dr Delbecq invited me as
a guest speaker in a later class, and eventually, I co-taught numerous courses with him. In this article, I describe my experience of Dr Delbecq’s unusual agency-oriented approach, as well as his reflections on my own management vision. I then describe how the lessons I learned while
working with Dr Delbecq have guided my subsequent efforts to make work more human-centered.
Exosomes from N‐Myc amplified neuroblastoma cells induce migration and confer chemoresistance to non‐N‐Myc amplified cells: implications of intra‐tumour heterogeneity
Authors: Fonseka Pamali , Liem Michael , Ozcitti Cemil , Adda Christopher G. , Ang Ching‐Seng , Mathivanan Suresh
Published: April 2019

Neuroblastoma accounts for 15% of childhood cancer mortality. Amplification of the oncogene N‐Myc is a well‐established poor prognostic marker for neuroblastoma. Whilst N‐Myc amplification status strongly correlates with higher tumour aggression and resistance to treatment, the role of N‐Myc in the aggressiveness of the disease is poorly understood. Exosomes are released by many cell types including cancer cells and are implicated as key mediators in cell‐cell communication via the transfer of molecular cargo. Hence, characterising the exosomal protein components from N‐Myc amplified and non‐amplified neuroblastoma cells will improve our understanding on their role in the progression of neuroblastoma. In this study, a comparative proteomic analysis of exosomes isolated from cells with varying N‐Myc amplification status was performed. Label‐free quantitative proteomic profiling revealed 968 proteins that are differentially abundant in exosomes released by the neuroblastoma cells. Gene ontology‐based analysis highlighted the enrichment of proteins involved in cell communication and signal transduction in N‐Myc amplified exosomes. Treatment of SH‐SY5Y cells with N‐Myc amplified SK‐N‐BE2 cell‐derived exosomes increased the migratory potential, colony forming abilities and conferred resistance to doxorubicin induced apoptosis. Incubation of exosomes from N‐Myc knocked down SK‐N‐BE2 cells abolished the transfer of resistance to doxorubicin induced apoptosis. These findings suggest that exosomes could play a pivotal role in N‐Myc‐driven aggressive neuroblastoma and transfer of chemoresistance between cells.

Abbreviations: RNA = ribonucleic acid; DNA = deoxyribonucleic acid; FCS = foetal calf serum; NTA = nanoparticle tracking analysis; LC‐MS = liquid chromatography–mass spectrometry; KD = knockdown; LTQ = linear trap quadropole; TEM = transmission electron microscopy
Risk measures and the distribution of damage curves for 600 European coastal cities
Authors: Abadie L M , Galarraga I , Markandya A , Sainz de Murieta E
Published: April 2019

A good understanding of climate change damages is vital to design effective adaptation policies and measures. Using a dataset of probabilistic sea-level rise and other of flood damages and protection cost curves for the 600 largest European coastal cities we generate stochastic damage curves and their distributions with and without adaptation. We apply the Generalized Extreme Value distribution to characterize the distributions and calculate two risk measures: the Value at Risk and the Expected Shortfall, which contribute to understanding the magnitude and probability of high-end sea-level rise represented by the upper tail of the distribution. This allows the costs of sea-level rise to be estimated (that is, in addition to other costs related to coastal extreme events) and supports decision-makers in integrating the high uncertainty related to future projections. This knowledge is necessary for an adequate risk management that does not underestimate risk. Furthermore, it allows city planners to tailor their risk tolerance. A great number of cities in Europe are currently undertaking adaptation plans or have already done so. Making these findings available should therefore be of great priority value to inform these processes.
Innovative consumers: ecological, behavioral, and physiological predictors of responses to novel food
Authors: Prasher Sanjay , Thompson Megan J , Evans Julian C , El-Nachef Michael , Bonier Frances , Morand-Ferron Julie
Published: April 2019

Consumer innovation, that is, the acquisition and consumption of novel food types, has received little attention, despite its predominance among animal innovations and its potential implications for the ecology and evolution of species in a changing world. Results of the few studies that have investigated individual responses to novel foods suggest that various ecological, behavioral, and physiological variables may affect individual propensity for consumer innovation, but further work is needed to clarify these relationships. We investigated whether urbanization, social rank, exploratory personality, and baseline levels of corticosterone predict food neophobia and consumer innovation responses of wild-caught black-capped chickadees (N = 170) from 14 sites along an urbanization gradient. Our analyses do not support a link between food neophobia or consumer innovation and urbanization, dominance, or exploratory personality. However, birds with higher levels of baseline corticosterone were quicker to contact novel food types, and more likely to consume novel foods than individuals with lower levels of the hormone. This finding suggests that physiological states that promote foraging behavior might drive individual responses to novel food. Additionally, we found that chickadees tested later in autumn were less neophobic than those tested earlier in the season, perhaps reflecting seasonal changes in food availability. Together, the ability of baseline corticosterone and date of capture to predict responses to novel food suggest that necessity may drive consumer innovation in chickadees.
Discovering novel mutation signatures by latent Dirichlet allocation with variational Bayes inference
Authors: Matsutani Taro , Ueno Yuki , Fukunaga Tsukasa , Hamada Michiaki
Published: April 2019

Motivation

A cancer genome includes many mutations derived from various mutagens and mutational processes, leading to specific mutation patterns. It is known that each mutational process leads to characteristic mutations, and when a mutational process has preferences for mutations, this situation is called a ‘mutation signature.’ Identification of mutation signatures is an important task for elucidation of carcinogenic mechanisms. In previous studies, analyses with statistical approaches (e.g. non-negative matrix factorization and latent Dirichlet allocation) revealed a number of mutation signatures. Nonetheless, strictly speaking, these existing approaches employ an ad hoc method or incorrect approximation to estimate the number of mutation signatures, and the whole picture of mutation signatures is unclear.

Results

In this study, we present a novel method for estimating the number of mutation signatures—latent Dirichlet allocation with variational Bayes inference (VB-LDA)—where variational lower bounds are utilized for finding a plausible number of mutation patterns. In addition, we performed cluster analyses for estimated mutation signatures to extract novel mutation signatures that appear in multiple primary lesions. In a simulation with artificial data, we confirmed that our method estimated the correct number of mutation signatures. Furthermore, applying our method in combination with clustering procedures for real mutation data revealed many interesting mutation signatures that have not been previously reported.

Availability and implementation

All the predicted mutation signatures with clustering results are freely available at http://www.f.waseda.jp/mhamada/MS/index.html. All the C++ source code and python scripts utilized in this study can be downloaded on the Internet (https://github.com/qkirikigaku/MS_LDA).

Supplementary information

Supplementary data are available at Bioinformatics online.
Lookback-Guess-Next Optimizer: Feedback-Guided Random Search Technique with Biased Mapping for Solving Unconstrained Optimization Problems
Authors: Al-Muhammed Muhammed Jassem
Published: April 2019

Finding global optima for functions is a very important problem. Although a large number of methods have been proposed for solving this problem, more effective and efficient methods are greatly required. This paper proposes an innovative method that combines different effective techniques for speeding up the convergence to the solution and greatly improving its precision. In particular, the method uses feedback-guided random search technique to identify the promising regions of the domains and uses the biased mapping technique to focus the search on these promising regions, without ignoring the other regions of the domains. Therefore, at any point of time, the domain of each variable is entirely covered with much more emphasis on the promising regions. Experiments with our prototype implementation showed that our method is efficient, effective, and outperformed the state-of-art techniques.
Web elements for health promotion in Malaysia
Authors: Noman Marwan , Koo Ah Choo , Tee Sim Hui , Krishnan Manimaran
Published: April 2019

The needs for health promotion is increasingly important for Malaysian. Government invests in the development to improve health education. Malaysia lacks the development of online solutions to help to maintain the health of the nation through prevention and mass education. This paper addresses important questions about the development of those health promotion websites by considering the motivation of web elements. It seeks to provide information on the barriers to the use and success as a method of health promotion. The empirical work is a perceptions study that aims to identify the barriers of web-based health promotion in the different user characteristics for health promotion purposes. This work is a qualitative research project directed at ascertaining the perceptions of Malaysians concerning the use of health promotion websites. It pertains to those factors which stop the uptake of website use and seeks to discern the views of users on how the health promotion websites may be more engaging. The principal finding is that the ethnicity of the user is mainly relevant in terms of the socio-economic status of the user. Users across all ethnicities respond to the same qualities of websites. The same web elements are motivating to users regardless of the characteristics of the users because the uptake of the Internet and the use of websites for health promotion has been more a phenomenon of the young. The study concludes with some recommendations for the Ministry of Health and the developers of health promotion websites in Malaysia.
Human papillomavirus vaccination among diverse college students in the state of Georgia: who receives recommendation, who initiates and what are the reasons?
Authors: Vu Milkie , Bednarczyk Robert A , Escoffery Cam , Getachew Betelihem , Berg Carla J
Published: April 2019

Young adulthood is a critical time for catch-up HPV vaccination. We assessed predictors of vaccine recommendation and initiation among college students. We analysed cross-sectional surveys from 2397 students using multivariable logistic regressions. Guided by the Socio-ecological and Health Belief Models, measures included socio-demographic characteristics, intrapersonal measures (e.g. vaccine beliefs), interpersonal measures (e.g. doctor’s recommendation) and institutional-level measures (e.g. college settings). The sample included students from private, public, technical and historically black colleges/universities. Of the sample, 64.5% were White; additionally, 48.3% of women (n = 750/1552) and 18.8% of men (n = 159/845) received a doctor’s recommendation. Among women, predictors included older age, US-born, higher parental education and attending private schools. Among men, predictors included younger age, being homosexual and attending private schools. HPV vaccine series initiation was low—43.3% of women (n = 672) and 16.7% of men (n = 141). Doctor’s recommendation predicted initiation for both sexes. Younger women, women attending technical colleges and men of ‘multiple/other’ race had lower odds of initiation. Common initiation barriers for both sexes included a lack of doctor recommendation and sexual inactivity. These barriers and the associations between nativity, race and socio-economic status with vaccine recommendation and initiation should be further investigated. Interventions should improve patient–provider communication around HPV vaccine.
Design and training effects of a physical reality simulator for minimally invasive mitral valve surgery
Authors: Jebran Ahmad-Fawad , Saha Shekhar , Waezi Narges , Al-Ahmad Ammar , Niehaus Heidi , Danner Bernhard C , Baraki Hassina , Kutschka Ingo
Published: April 2019

OBJECTIVES

Minimally invasive mitral valve surgery (MIMVS) through an endoscopic right minithoracotomy is a well-established yet complex procedure that has a challenging learning curve. We have developed a simulator for MIMVS and evaluated its short- and long-term training effects.

METHODS

Trainees without simulator experience or training in MIMVS were divided into 2 groups (10 students and 10 residents) and participated in a 5-day training course after initial instruction. Each trainee performed a ring annuloplasty. Scores were given by a supervisor who assessed 5 skills. The duration of each procedure was also measured. To evaluate the long-term effect of the training course, trainees performed the same procedure 4 weeks after the last session.

RESULTS

Trainees in the resident group were significantly older compared to those in the student group and had a mean surgical experience of 4.4 ± 0.78 years standard error of the mean. All other demographic data were similar. Significant learning curves could be achieved in both groups over the course of 5 days with regard to total skill scores and total duration. However, when we compared the learning curves of both groups, no significant difference could be seen. Long-term performance in both groups was still significantly better compared to that in the first training session.

CONCLUSIONS

Training with our simulator provided a significant enhancement of a trainee’s performance. This learning effect was achieved in both groups and was still evident 4 weeks later. We strongly recommend our simulator for simulation-based surgical education of cardiac surgeons interested in MIMVS.
Colorectal cancer susceptibility variants and risk of conventional adenomas and serrated polyps: results from three cohort studies
Authors: Hang Dong , Joshi Amit D , He Xiaosheng , Chan Andrew T , Jovani Manol , Gala Manish K , Ogino Shuji , Kraft Peter , Turman Constance , Peters Ulrike , Bien Stephanie A , Lin Yi , Hu Zhibin , Shen Hongbing , Wu Kana , Giovannucci Edward L , Song Mingyang
Published: April 2019

Background

Increasing evidence suggests that conventional adenomas (CAs) and serrated polyps (SPs) represent two distinct groups of precursor lesions for colorectal cancer (CRC). The influence of common genetic variants on risk of CAs and SPs remain largely unknown.

Methods

Among 27 426 participants within three prospective cohort studies, we created a weighted genetic risk score (GRS) based on 40 CRC-related single nucleotide polymorphisms (SNPs) identified in previous genome-wide association studies; and we examined the association of GRS (per one standard deviation increment) with risk of CAs, SPs and synchronous CAs and SPs, by multivariable logistic regression. We also analysed individual variants in the secondary analysis.

Results

During 18–20 years of follow-up, we documented 2952 CAs, 1585 SPs and 794 synchronous CAs and SPs. Higher GRS was associated with increased risk of CAs [odds ratio (OR) = 1.17, 95% confidence interval (CI): 1.12-1.21] and SPs (OR = 1.09, 95% CI: 1.03-1.14), with a stronger association for CAs than SPs (Pheterogeneity=0.01). An even stronger association was found for patients with synchronous CAs and SPs (OR = 1.32), advanced CAs (OR = 1.22) and multiple CAs (OR = 1.25). Different sets of variants were associated with CAs and SPs, with a Spearman correlation coefficient of 0.02 between the ORs associating the 40 SNPs with the two lesions. After correcting for multiple testing, three variants were associated with CAs (rs3802842, rs6983267 and rs7136702) and two with SPs (rs16892766 and rs4779584).

Conclusions

Common genetic variants play a potential role in the conventional and serrated pathways of CRC. Different sets of variants are identified for the two pathways, further supporting the aetiological heterogeneity of CRC.
Phase 1 Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects
Authors: Adler Stuart P , Lewis Nicole , Conlon Anthony , Christiansen Mark P , Al-Ibrahim Mohamed , Rupp Richard , Fu Tong-Ming , Bautista Oliver , Tang Huaping , Wang Dai , Fisher Alison , Culp Timothy , Das Rituparna , Beck Karen , Tamms Gretchen , Musey Luwy ,   V160-001 Study Group
Published: April 2019

Background

A conditionally replication-defective human cytomegalovirus (CMV) vaccine (V160) derived from AD169 and genetically engineered to express CMV pentameric complex (gH/gL/pUL128/pUL130/pUL131) was developed and evaluated for phase 1 vaccine safety and immunogenicity in CMV-seronegative and CMV-seropositive adults.

Methods

Subjects received 3 doses of V160 or placebo on day 1, month 1, and month 6. Four vaccine dose levels, formulated with or without aluminum phosphate adjuvant, were evaluated. Injection-site and systemic adverse events (AEs) and vaccine viral shedding were monitored. CMV-specific cellular and humoral responses were measured by interferon-gamma ELISPOT and virus neutralization assay up to 12 months after last dose.

Results

V160 was generally well-tolerated, with no serious AEs observed. Transient, mild-to-moderate injection-site and systemic AEs were reported more frequently in vaccinated subjects than placebo. Vaccine viral shedding was not detected in any subject, confirming the nonreplicating feature of V160. Robust neutralizing antibody titers were elicited and maintained through 12 months postvaccination. Cellular responses to structural and nonstructural viral proteins were observed, indicating de novo expression of viral genes postvaccination.

Conclusions

V160 displayed an acceptable safety profile. Levels of neutralizing antibodies and T-cell responses in CMV-seronegative subjects were within ranges observed following natural CMV infection.

Clinical Trial Registration

. NCT01986010.
Metabolic interventions for the prevention and treatment of daptomycin non-susceptibility in Staphylococcus aureus
Authors: Reed Joseph M , Gardner Stewart G , Mishra Nagendra N , Bayer Arnold S , Somerville Greg A
Published: April 2019

Background

A major developing problem in the treatment of Staphylococcus aureus infections is the emergence of resistance during treatment with daptomycin. Previous metabolomic analyses of isogenic S. aureus strains prior to and after evolution into a daptomycin non-susceptible (DapNS) state provided important metabolic information about this transition (e.g. perturbations of the tricarboxylic acid cycle).

Objectives

To assess the significance of these metabolic changes, in vitro susceptibility to daptomycin was determined in daptomycin-susceptible (DapS) and DapNSS. aureus strains cultivated with metabolic inhibitors targeting these changes.

Methods

Only inhibitors that are approved for use in humans were chosen (i.e. fosfomycin, valproate, trimetazidine and 6-mercaptopurine) to assess the importance of metabolic pathways for daptomycin non-susceptibility. The ability of these inhibitors to forestall the emergence of DapNS strains was also assessed.

Results

The combination of daptomycin and fosfomycin synergistically killed both DapS and DapNS strains in vitro and enhanced the in vivo outcome against a DapNS strain in experimental endocarditis. Interestingly, fosfomycin acts on the peptidoglycan biosynthetic enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA); however, it also had a significant effect on the enzymatic activity of enolase, an essential enzyme in S. aureus. While fosfomycin acted synergistically with daptomycin, it failed to prevent the in vitro evolution of daptomycin non-susceptibility. In contrast, trimetazidine, an anti-angina drug that stimulates glucose oxidation, abolished the ability of DapSS. aureus strains to transition to a DapNS state.

Conclusions

These data reveal that metabolic adaptations associated with DapNS strains can be targeted to prevent the emergence of and/or reverse pre-existing resistance to daptomycin.
The evolution of power in the global coffee value chain and production network
Authors: Grabs Janina , Ponte Stefano
Published: April 2019

The configurations of global value chains and production networks are constantly changing, leading to new trajectories and geographical distributions of value creation and capture. In this article, we offer a 40-year evolutionary perspective on power and governance in the global coffee value chain and production network. We identify three distinct phases that are characterised by different power dynamics, governance setups and distributional configurations. We find that the kinds of power exercised along the coffee chain have changed, but also that the underlying power inequities between Northern buyers and Southern producers have remained fundamentally unaltered.
The stomatal flexoskeleton: how the biomechanics of guard cell walls animate an elastic pressure vessel
Authors: Yi Hojae , Chen Yintong , Wang James Z , Puri Virendra M , Anderson Charles T
Published: April 2019

In plants, stomatal guard cells are one of the most dynamic cell types, rapidly changing their shape and size in response to environmental and intrinsic signals to control gas exchange at the plant surface. Quantitative and systematic knowledge of the biomechanical underpinnings of stomatal dynamics will enable strategies to optimize stomatal responsiveness and improve plant productivity by enhancing the efficiency of photosynthesis and water use. Recent developments in microscopy, mechanical measurements, and computational modeling have revealed new insights into the biomechanics of stomatal regulation and the genetic, biochemical, and structural origins of how plants achieve rapid and reliable stomatal function by tuning the mechanical properties of their guard cell walls. This review compares historical and recent experimental and modeling studies of the biomechanics of stomatal complexes, highlighting commonalities and contrasts between older and newer studies. Key gaps in our understanding of stomatal functionality are also presented, along with assessments of potential methods that could bridge those gaps.
Chromoblastomycosis in the Amazon region, Brazil, caused by Fonsecaea pedrosoi, Fonsecaea nubica, and Rhinocladiella similis: Clinicopathology, susceptibility, and molecular identification
Authors: Andrade Tânia Sueli de , de Almeida Ana Maria Zimmer , Basano Sergio de Almeida , Takagi Elizabeth Harummyy , Szeszs Maria Walderez , Melhem Marcia S C , Albuquerque Madson , Camargo Juliana de Souza Almeida Aranha , Gambale Walderez , Camargo Luís Marcelo Aranha
Published: April 2019

Chromoblastomycosis is a chronic subcutaneous disease caused by human contact with melanized fungi occurring mainly in tropical and subtropical zones worldwide. This study assessed 12 patients with chromoblastomycosis from Rondônia, Brazil, Amazon region. In sum, 83.3% were men, 41.6% were from Monte Negro city, median age was 52.9 years, and median time to disease progression was 12.2 years. Lesions were located on the lower limbs (75%), and verruciform was prevalent form (66.6%). After 3 years of treatment with itraconazole, two patients were considered cured. The etiological agents were identified by the molecular sequence of the ribosomal internal transcribed spacer ITS1, 5.8S, and ITS2 region and β-tubulin genes. Eight strains were identified as Fonsecaea pedrosoi, two were F. nubica, and two were Rhinocladiella similis. The antifungal activity of five drugs was evaluated, and the most active drug was terbinafine (range minimal inhibitory concentration [MIC] 0.015–0.12 μg/ml), itraconazole (range MIC 0.03–0.5 μg/ml) and voriconazole (range MIC 0.06–0.5 μg/ml). The highest MIC was 5-fluorocytosine (range MIC 2–32 μg/ml), and amphotericin B (range MIC 0.25–2 μg/ml). In conclusion, the present study expanded the epidemiological disease database and described for the first time F. nubica and R. similis as chromoblastomycosis agents in the Brazilian Amazon region. Our results confirmed the importance of using molecular methods to identify the melanized fungi and stimulate the recognition of the disease in other places where no cases have been reported.
Probing gas disc physics with LISA: simulations of an intermediate mass ratio inspiral in an accretion disc
Authors: Derdzinski A M , D’Orazio D , Duffell P , Haiman Z , MacFadyen A
Published: April 2019

The coalescence of a compact object with a $10^{4}\hbox{--}10^{7}\, {\rm M_\odot }$ supermassive black hole (SMBH) produces mHz gravitational waves (GWs) detectable by the future Laser Interferometer Space Antenna (LISA). If such an inspiral occurs in the accretion disc of an active galactic nucleus (AGN), the gas torques imprint a small deviation in the GW waveform. Here, we present two-dimensional hydrodynamical simulations with the moving-mesh code disco of a BH inspiraling at the GW rate in a binary system with a mass ratio q = M2/M1 = 10−3, embedded in an accretion disc. We assume a locally isothermal equation of state for the gas (with Mach number $\mathcal {M}=20$) and implement a standard α-prescription for its viscosity (with α = 0.03). We find disc torques on the binary that are weaker than in previous semi-analytic toy models, and are in the opposite direction: the gas disc slows down, rather than speeds up the inspiral. We compute the resulting deviations in the GW waveform, which scale linearly with the mass of the disc. The SNR of these deviations accumulates mostly at high frequencies, and becomes detectable in a 5 yr LISA observation if the total phase shift exceeds a few radians. We find that this occurs if the disc surface density exceeds $\Sigma _0 \gtrsim 10^{2-3}\rm g\, cm^{-2}$, as may be the case in thin discs with near-Eddington accretion rates. Since the characteristic imprint on the GW signal is strongly dependent on disc parameters, a LISA detection of an intermediate mass ratio inspiral would probe the physics of AGN discs and migration.
Driver safety in patients with primary brain tumors
Authors: Estevis Eduardo , Noll Kyle R , Bradshaw Mariana E , Wefel Jeffrey S
Published: April 2019

Background

Operating a motor vehicle involves multiple cognitive and sensorimotor faculties. Neurological conditions pose driving risk, but this has not been examined in patients with primary brain tumors.

Methods

Sixty-four patients with primary brain tumors (32 left hemisphere; 69% glioblastoma) completed the Cognitive Behavioral Driver’s Inventory (CBDI). A subset also completed broader cognitive testing. Patient characteristics, CBDI measures, and broader neuropsychological test scores were compared between Passing and Nonpassing groups. Follow-up logistic regression analyses identified patient characteristics and CBDI measures predictive of Pass/Nonpass outcome. Point-biserial correlations determined associations between neuropsychological tests and CBDI outcome.

Results

Sixty-nine percent of patients were classified as passing the CBDI. Nonpassing patients were older and more likely to have WHO grade IV and temporal lobe tumors. Age was the most salient predictor of CBDI performance. CBDI measures of speeded visual search and set-shifting, speeded response inhibition, vigilance and freedom from distractibility, and basic visual scanning speed were predictive of Pass/Nonpass outcome. Neuropsychological tests of memory in particular, but also speeded visual scanning and discrimination, executive function, basic visual attention, visuoconstruction, and manual dexterity (dominant hand), were associated with CBDI outcome.

Conclusions

A sizeable proportion of patients with primary brain tumors appear at risk of driving difficulty, particularly those with higher-grade tumors and of older age. Memory, visual attention, and executive difficulties appear to contribute most to driving safety risk as determined by the CBDI. These results highlight the importance of driving safety screening in this population.
Social Work Is a Human Rights Profession
Authors: Mapp Susan , McPherson Jane , Androff David , Gatenio Gabel Shirley
Published: April 2019

As defined by the International Federation of Social Workers, social work is a human rights profession. This is explicitly stated in the professional codes of ethics in many nations. However, the most recent version of the Code of Ethics of the National Association of Social Workers continues to exclude any mention of human rights, fitting in with the history of U.S. exceptionalism on this subject. Social workers around the world have a long history of working for the achievement of human rights, including an explicit grounding of practice in human rights principles: human dignity, nondiscrimination, participation, transparency, and accountability. Utilizing these principles, U.S. social workers can move from the deficit model of the needs-based approach to competently contextualizing individual issues in their larger human rights framework. In this way, social work can address larger social problems and make way for the concurrent achievement of human rights. This article explains these principles and provides a case example of how to apply them in practice.
Rapid Detection of Monilinia fructicola and Monilinia laxa on Peach and Nectarine using Loop-Mediated Isothermal Amplification
Authors: Ortega Sara Franco , del Pilar Bustos López Maria , Nari Luca , Boonham Neil , Gullino Maria Lodovica , Spadaro Davide
Published: April 2019

Monilinia laxa and M. fructicola are two causal agents of brown rot, one of the most important diseases in stone fruit. Two species cause blight on blossoms and twigs and brown rot on fruit in pre- and postharvest. Both species are distributed worldwide in North and South America, Australia, and Japan. In Europe, M. laxa is endemic, while M. fructicola was introduced in 2001 and it is now widespread in several countries. Currently, both species coexist in European stone fruit orchards. Monilinia spp. overwinter in cankers and mummified fruit. Mummy monitoring during winter permits growers to understand which species of Monilinia will be prevalent in an orchard during the following season, permitting planning of an appropriate crop protection. Traditionally, the identification has been carried out using morphological features and even with polymerase chain reaction (PCR)-based assays that requires time and well-equipped laboratories. In this study, two isothermal-based methods were designed to identify these pathogens in a faster way than using traditional methods. The loop-mediated amplification (LAMP) assays were validated on some isolates of Monilinia spp. coming from the mummy monitoring according to the international European and Mediterranean Plant Protection Organization standard (PM7/98), taking into account specificity, sensitivity, repeatability, and reproducibility. The sensitivity of both assays was checked by monitoring (at different time points) two nectarine varieties artificially inoculated and stored at two different temperatures. The reliability of both LAMP assays against the quantification of the inoculum was compared with previously published quantitative PCR assays. Both LAMP methods were able to detect a low number of cells. These LAMP methods could be a useful tool for monitoring brown rot causal agents in the field and during postharvest.
An Improved Evans Blue Staining Method for Consistent, Accurate Assessment of Plasmodiophora brassicae Resting Spore Viability
Authors: Harding M. W. , Hill T. B. , Yang Y. , Daniels G. C. , Hwang S. F. , Strelkov S. E. , Howard R. J. , Feng J.
Published: April 2019

Clubroot caused by Plasmodiophora brassicae is an important disease of brassica crops. The use of vital stains to determine the viability of P. brassicae resting spores can provide useful information regarding spore longevity, inoculum potential, or the efficacy of antimicrobial treatments. Evans blue is one example of a vital stain that has been reported to differentially stain viable and nonviable resting spores. Some previously published protocols using Evans blue to stain P. brassicae resting spores have not provided accurate or consistent results. In this study, we modified the Evans blue method by increasing the staining time to 8 h or more and evaluated P. brassicae resting spores after heat treatment at various combinations of temperature and time. Extending staining times significantly increased the numbers of stained resting spores up to 7 h, after which the numbers of stained spores did not change significantly (R2 = 96.88; P ≤ 0.001). The accuracy of the modified method to discriminate viable and nonviable spores was evaluated in repeated experiments and by comparing the staining data with those derived from inoculation assays and propidium monoazide quantitative PCR (qPCR). The results demonstrated that the modified Evans blue staining method improved the accuracy and consistency of measurement of P. brassicae resting spore viability. Additionally, it was equivalent to the qPCR method for differentiating viable and nonviable spores (R2 = 99.84; P ≤ 0.001) and confirmed in canola infection bioassays.