bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Royal Navy award: The Edward Leicester Atkinson prize
Authors: Tarver Michael C.
Published: October 2018

More than 100 years have now passed since Scott’s Terra Nova expedition to the Antarctic, which was quickly followed by the First World War. Out of the events of those times emerges the name of Edward Leicester Atkinson, the Royal Navy Surgeon and Antarctic explorer who was a member of the scientific staff of Scott’s expedition, and who went on to serve in the First World War. In his honour, the Edward Leicester Atkinson Prize will be awarded annually to a Royal Navy Medical Officer who displays the values of leadership and moral courage during the New Entry Medical Officer course, either at Britannia Royal Naval College or the Institute of Naval Medicine.
Adults’ sensitivity to graphotactic differences within the English vocabulary
Authors: TREIMAN REBECCA , DECKER KRISTINA , KESSLER BRETT
Published: October 2018

Linguists have described the English vocabulary as including Latinate and basic subsystems. In three experiments with a total of 93 participants, we asked whether skilled readers are sensitive to graphotactic differences between these systems. Participants saw pairs of nonwords and were asked to choose the item in each pair that appeared more wordlike. Participants were more likely to select an item with an onset and an ending that suggested the same system than an item with a mismatch. Participants also used the presence of a single versus double medial consonant as a marker of the system to which an item belongs. The results suggest that skilled readers have learned about some of the graphotactic differences between Latinate and basic words and do not treat English as a monolithic system.
An optimal trajectory planning method for path tracking of industrial robots
Authors: Luo Xianxi , Li Shuhui , Liu Shubo , Liu Guoquan
Published: October 2018

This paper presents an optimal trajectory planning method for industrial robots. The paper specially focuses on the applications of path tracking. The problem is to plan the trajectory with a specified geometric path, while allowing the position and orientation of the path to be arbitrarily selected within the specific ranges. The special contributions of the paper include (1) an optimal path tracking formulation focusing on the least time and energy consumption without violating the kinematic constraints, (2) a special mechanism to discretize a prescribed path integration for segment interpolation to fulfill the optimization requirements of a task with its constraints, (3) a novel genetic algorithm (GA) optimization approach that transforms a target path to be tracked as a curve with optimal translation and orientation with respect to the world Cartesian coordinate frame, (4) an integration of the interval analysis, piecewise planning and GA algorithm to overcome the challenges for solving the special trajectory planning and path tracking optimization problem. Simulation study shows that it is an insufficient condition to define a trajectory just based on the consideration that each point on the trajectory should be reachable. Simulation results also demonstrate that the optimal trajectory for a path tracking problem can be obtained effectively and efficiently using the proposed method. The proposed method has the properties of broad adaptability, high feasibility and capability to achieve global optimization.
RESPONSE TO OUR COMMENTATORS ON THE REPORT OF THE INTERNATIONAL PANEL ON SOCIAL PROGRESS 2018
Authors: Adler Matthew , Fleurbaey Marc
Published: October 2018

The contributors to this symposium have brought up many important points in their discussions of five chapters of the Report, and we are very grateful to them. Since the authors of the chapters would be better able to respond to many of the specific comments, we will confine ourselves here to a brief discussion of a few major issues highlighted by the contributors. We are in particular inspired by the following comments: Alina Rocha Menocal's point about the role of the state and committed elites; James Deane's description of the deep transformation of the media scene by new forms of communication; Uma Rani's emphasis on the importance of structural transformation and social care policies; and Diana Alarcon's call for paying greater attention to different levels of development and to macroeconomic policy.
COMMENTS ON THE REPORT OF THE INTERNATIONAL PANEL ON SOCIAL PROGRESS CHAPTER 13: MEDIA AND COMMUNICATIONS
Authors: Deane James
Published: October 2018

Chapter 13 covers a broad waterfront, encompassing digital transformation, the unevenness in access to new technologies, the complex power dynamics that underpin the new media and communication space, the shifting role of journalism in enabling (or not) public knowledge, and the challenges and opportunities for social progress in media access, with particular attention focused on the role of citizen journalism and alternative media.
COMMENT ON THE REPORT OF THE INTERNATIONAL PANEL ON SOCIAL PROGRESS, CHAPTER 3: ECONOMIC INEQUALITY AND SOCIAL PROGRESS
Authors: Rani Uma
Published: October 2018

Chapter 3 discusses the causes, patterns and dynamics of inequalities in an exhaustive review of the literature on inequality of income, expenditure and wealth among individuals and households. It emphasizes how these inequalities reflect and affect inequality along various dimensions, including political freedom, economic opportunity, health, education and social outcomes. It gives three sets of policy recommendations for different populations: (i) policies to improve the conditions among the poor, the vulnerable and the socially excluded; (ii) policies geared towards supporting the growth and sustainability of a strong middle class; and (iii) policies that seek to curb concentration of income and wealth at the top (121). Some of these policy recommendations are quite consistent with what has often been proposed for the past three decades, which is that redistributive policies or welfare at the bottom should benefit the least well-off and address inequality.
Small Sets of Novel Words Are Fully Retained After 1-Week in Typically Developing Children and Down Syndrome: A Fast Mapping Study
Authors: Sakhon Stella , Edwards Kelly , Luongo Alison , Murphy Melanie , Edgin Jamie
Published: October 2018

Objectives: Down syndrome (DS) is a population with known hippocampal impairment, with studies showing that individuals with DS display difficulties in spatial navigation and remembering arbitrary bindings. Recent research has also demonstrated the importance of the hippocampus for novel word-learning. Based on these data, we aimed to determine whether individuals with DS show deficits in learning new labels and if they may benefit from encoding conditions thought to be less reliant on hippocampal function (i.e., through fast mapping). Methods: In the current study, we examined immediate, 5-min, and 1-week delayed word-learning across two learning conditions (e.g., explicit encoding vs. fast mapping). These conditions were examined across groups (twenty-six 3- to 5-year-old typically developing children and twenty-six 11- to 28-year-old individuals with DS with comparable verbal and nonverbal scores on the Kaufman Brief Intelligence Test – second edition) and in reference to sleep quality. Results: Both individuals with and without DS showed retention after a 1-week delay, and the current study found no benefit of the fast mapping condition in either group contrary to our expectations. Eye tracking data showed that preferential eye movements to target words were not present immediately but emerged after 1-week in both groups. Furthermore, sleep measures collected via actigraphy did not relate to retention in either group. Conclusions: This study presents novel data on long-term knowledge retention in reference to sleep patterns in DS and adds to a body of knowledge helping us to understand the processes of word-learning in typical and atypically developing populations. (JINS, 2018, 24, 955–965)
Association between family dinner and BMI in adults: data from the 2013 to 2015 Korean National Health and Nutrition Examination Survey
Authors: Rah Woongchan , So Jaewon , Park Eun-Cheol , Lee Sang Ah , Jang Sung-In
Published: October 2018

Objective

People who eat alone, which is becoming a new trend owing to the increasing proportion of one-person households in Korea, are more likely to become overweight and obese. Therefore, we investigated the association between having a dinner companion and BMI.

Design

A linear regression model adjusted for covariates was utilized to examine the association between having a dinner companion and BMI. Subgroup analyses were performed, stratified by age group, gender, household income, educational level and occupation.

Setting

We used the data from the Korean Health and Nutrition Examination Survey VI. Our primary independent variable was having a dinner companion while the dependent variable was BMI.

Subjects

In total, 13303 individuals, aged 20 years or over, were analysed.

Results

Compared with the solo eating group, BMI was lower in the family dinner group (β=−0·39, P<0·01) but not in the non-family dinner group (β=−0·06, P=0·67). The subgroup analysis revealed that the difference in BMI was most significant in young generations, such as those aged 20–29 years (β=−1·15, P<0·01) and 30–39 years (β=−0·78, P=0·01).

Conclusions

We found that people who eat dinner alone are more likely to become overweight and obese than those who eat with their family. This association was stronger in males and young adults than their counterparts. Considering the increasing trends in the proportion of single-person households and solo eating, appropriate intervention is needed.
CROWLAND ABBEY AS ANGLO-SAXON SANCTUARY IN THE PSEUDO-INGULF CHRONICLE
Authors: BRADY LINDY
Published: October 2018

Crowland Abbey was one of many English monasteries after the Norman Conquest to forge documents that claimed a right to permanent sanctuary rooted in the Anglo-Saxon period. Yet Crowland's claims stand out because while other ecclesiastical chronicles that grounded their sanctuary claims in an earlier tradition did so in order to defend those rights in the twelfth century or later, Crowland never claimed this privilege for anything other than the abbey's Anglo-Saxon past. Indeed, I argue that the three forged “Anglo-Saxon” charters that make this assertion, which all appear in the Pseudo-Ingulf section of the abbey's chronicle, theHistoria Croylandensis, do so in order to emphasize a more fundamental claim about the institution's authority — its association with one of the most significant fenland saints, Guthlac. Moreover, I argue that the most likely date when this material was forged is the late twelfth century. In the context of the narrative in which they appear, these charters reveal that later medieval Crowland constructed a narrative that saw permanent sanctuary as an important feature of the abbey's Anglo-Saxon past.
METAPHYSICS AND TESTIMONIAL KNOWLEDGE IN THESUPER IOHANNEMOF ALBERT THE GREAT
Authors: CASTEIGT JULIE
Published: October 2018

This article examines Albert the Great's interpretation of John 1:7 concerning John the Baptist: “He came as a witness, to testify about the Light, so that all might believe through him.” Commenting on this verse, Albert develops the idea that the metaphysical approach to God, according to which the notion of God is purified of all sensory images, must be completed by a method that is more connatural to the human being: testimonial knowledge, that is, relying on the senses and imagination, using the metaphors that God himself has suggested through his revelation. Albert's reading of John 1:7 is found to be in continuity with key ideas elsewhere in his oeuvre.
Safety and efficacy of direct acting oral anticoagulants and vitamin K antagonists in nonvalvular atrial fibrillation – a network meta-analysis of real-world data
Authors: Hirschl Mirko , Kundi Michael
Published: October 2018

Abstract. Background: In randomized controlled trials (RCTs) direct acting oral anticoagulants (DOACs) showed a superior risk-benefit profile in comparison to vitamin K antagonists (VKAs) for patients with nonvalvular atrial fibrillation. Patients enrolled in such studies do not necessarily reflect the whole target population treated in real-world practice. Materials and methods: By a systematic literature search, 88 studies including 3,351,628 patients providing over 2.9 million patient-years of follow-up were identified. Hazard ratios and event-rates for the main efficacy and safety outcomes were extracted and the results for DOACs and VKAs combined by network meta-analysis. In addition, meta-regression was performed to identify factors responsible for heterogeneity across studies. Results: For stroke and systemic embolism as well as for major bleeding and intracranial bleeding real-world studies gave virtually the same result as RCTs with higher efficacy and lower major bleeding risk (for dabigatran and apixaban) and lower risk of intracranial bleeding (all DOACs) compared to VKAs. Results for gastrointestinal bleeding were consistently better for DOACs and hazard ratios of myocardial infarction were significantly lower in real-world for dabigatran and apixaban compared to RCTs. By a ranking analysis we found that apixaban is the safest anticoagulant drug, while rivaroxaban closely followed by dabigatran are the most efficacious. Risk of bias and heterogeneity was assessed and had little impact on the overall results. Analysis of effect modification could guide the clinical decision as no single DOAC was superior/inferior to the others under all conditions. Conclusions: DOACs were at least as efficacious as VKAs. In terms of safety endpoints, DOACs performed better under real-world conditions than in RCTs. The current real-world data showed that differences in efficacy and safety, despite generally low event rates, exist between DOACs. Knowledge about these differences in performance can contribute to a more personalized medicine.
Predictors of Posttraumatic Growth in Adults Bereaved by Suicide
Authors: Drapeau Christopher W. , Lockman Jennifer D. , Moore Melinda M. , Cerel Julie
Published: October 2018

Abstract. Background: Although suicide loss has been associated with several negative outcomes, numerous studies have shown that loss survivors can experience posttraumatic growth (PTG) following the suicide loss of a significant other. However, few studies have explored the mechanisms of such growth. Aims: The aim of this study was to identify predictors of PTG among a sample of adult suicide loss survivors and to explore whether the amount of time since the suicide loss moderated the relation between self-reported coping and PTG. Method: Suicide-bereaved adults (n = 307) completed online questionnaires measuring personality, coping, help-seeking attitudes, social support, and PTG. Results: Hierarchical regression analyses showed five independent associations with PTG: time since loss, perceived closeness, help-seeking attitudes, social support, and problem-focused coping. Time since loss did not moderate the relation between any of the self-reported coping styles and PTG. Limitations: The limitations of this study include a cross-sectional design, potential selection bias, no comparison or control group, and unrepresentative sample demographics of suicide loss survivors. Conclusion: Problem-focused coping showed the strongest association with PTG, independent of time since loss, suggesting that this coping style may facilitate growth throughout the grief trajectory.
Minimizing Common Errors When Projecting Geospatial Data Onto a Vortex‐Centered Space
Authors: Ahern Kyle , Cowan Levi
Published: October 2018

The problem of transforming geospatial data into polar coordinates, a common task in the analysis of data centered on geophysical phenomena, is examined. The azimuthal equidistant projection is shown to be the optimal transform for this purpose. A mathematical and observational analysis of the errors incurred by using a common alternative transform is conducted and reveals that such errors can be significant at radii as small as a few hundred kilometers. When evaluating observed 200‐hPa wind fields near Atlantic tropical cyclones (TCs), median azimuthal maximum errors in total and radial wind range up to 10% within 700 km of the TC and up to 50% within 1,600 km of the TC. Errors are shown to depend strongly on the statistical characteristics of the data set and increase nonlinearly with latitude and radius.
AirSWOT InSAR Mapping of Surface Water Elevations and Hydraulic Gradients Across the Yukon Flats Basin, Alaska
Authors: Pitcher Lincoln H. , Pavelsky Tamlin M. , Smith Laurence C. , Moller Delwyn K. , Altenau Elizabeth H. , Allen George H. , Lion Christine , Butman David , Cooley Sarah W. , Fayne Jessica V. , Bertram Mark
Published: October 2018

AirSWOT, an experimental airborne Ka‐band interferometric synthetic aperture radar, was developed for hydrologic research and validation of the forthcoming Surface Water and Ocean Topography (SWOT) satellite mission (to be launched in 2021). AirSWOT and SWOT aim to improve understanding of surface water processes by mapping water surface elevation (WSE) and water surface slope (WSS) in rivers, lakes, and wetlands. However, the utility of AirSWOT for these purposes remains largely unexamined. We present the first investigation of AirSWOT WSE and WSS surveys over complex, low‐relief, wetland‐river hydrologic environments, including (1) a field‐validated assessment of AirSWOT WSE and WSS precisions for lakes and rivers in the Yukon Flats Basin, an Arctic‐Boreal wetland complex in eastern interior Alaska; (2) improved scientific understanding of surface water flow gradients and the influence of subsurface permafrost; and (3) recommendations for improving AirSWOT precisions in future scientific and SWOT validation campaigns. AirSWOT quantifies WSE with an RMSE of 8 and 15 cm in 1 and 0.0625 km2 river reaches, respectively, and 21 cm in lakes. This indicates good utility for studying hydrologic flux, WSS, geomorphic processes, and coupled surface/subsurface hydrology in permafrost environments. This also suggests that AirSWOT supplies sufficient precision for validating SWOT WSE and WSS over rivers, but not lakes. However, improvements in sensor calibration and flight experiment design may improve precisions in future deployments as may modifications to data processing. We conclude that AirSWOT is a useful tool for bridging the gap between field observations and forthcoming global SWOT satellite products.
Spin-controlled wavefront shaping with plasmonic chiral geometric metasurfaces
Authors: Chen Yang , Yang Xiaodong , Gao Jie
Published: October 2018

Metasurfaces, as a two-dimensional (2D) version of metamaterials, have drawn considerable attention for their revolutionary capability in manipulating the amplitude, phase, and polarization of light. As one of the most important types of metasurfaces, geometric metasurfaces provide a versatile platform for controlling optical phase distributions due to the geometric nature of the generated phase profile. However, it remains a great challenge to design geometric metasurfaces for realizing spin-switchable functionalities because the generated phase profile with the converted spin is reversed once the handedness of the incident beam is switched. Here, we propose and experimentally demonstrate chiral geometric metasurfaces based on intrinsically chiral plasmonic stepped nanoapertures with a simultaneously high circular dichroism in transmission (CDT) and large cross-polarization ratio (CPR) in transmitted light to exhibit spin-controlled wavefront shaping capabilities. The chiral geometric metasurfaces are constructed by merging two independently designed subarrays of the two enantiomers for the stepped nanoaperture. Under a certain incident handedness, the transmission from one subarray is allowed, while the transmission from the other subarray is strongly prohibited. The merged metasurface then only exhibits the transmitted signal with the phase profile of one subarray, which can be switched by changing the incident handedness. Based on the chiral geometric metasurface, both chiral metasurface holograms and the spin-dependent generation of hybrid-order Poincaré sphere beams are experimentally realized. Our approach promises further applications in spin-controlled metasurface devices for complex beam conversion, image processing, optical trapping, and optical communications.
Active pathways of anaerobic methane oxidation across contrasting riverbeds
Authors: Shen Li-dong , Ouyang Liao , Zhu Yizhu , Trimmer Mark
Published: October 2018

Anaerobic oxidation of methane (AOM) reduces methane emissions from marine ecosystems but we know little about AOM in rivers, whose role in the global carbon cycle is increasingly recognized. We measured AOM potentials driven by different electron acceptors, including nitrite, nitrate, sulfate, and ferric iron, and identified microorganisms involved across contrasting riverbeds. AOM activity was confined to the more reduced, sandy riverbeds, whereas no activity was measured in the less reduced, gravel riverbeds where there were few anaerobic methanotrophs. Nitrite-dependent and nitrate-dependent AOM occurred in all sandy riverbeds, with the maximum rates of 61.0 and 20.0 nmol CO2 g−1 (dry sediment) d−1, respectively, while sulfate-dependent and ferric iron-dependent AOM occurred only where methane concentration was highest and the diversity of AOM pathways greatest. Diverse Candidatus Methylomirabilis oxyfera (M. oxyfera)-like bacteria and Candidatus Methanoperedens nitroreducens (M. nitroreducens)-like archaea were detected in the sandy riverbeds (16S rRNA gene abundance of 9.3 × 105 to 1.5 × 107 and 2.1 × 104 to 2.5 × 105 copies g−1 dry sediment, respectively) but no other known anaerobic methanotrophs. Further, we found M. oxyfera-like bacteria and M. nitroreducens-like archaea to be actively involved in nitrite- and nitrate/ferric iron-dependent AOM, respectively. Hence, we demonstrate multiple pathways of AOM in relation to methane, though the activities of M. oxyfera-like bacteria and M. nitroreducens-like archaea are dominant.
IL-38 has an anti-inflammatory action in psoriasis and its expression correlates with disease severity and therapeutic response to anti-IL-17A treatment
Authors: Mercurio Laura , Morelli Martina , Scarponi Claudia , Eisenmesser Elan Z. , Doti Nunzianna , Pagnanelli Gianluca , Gubinelli Emanuela , Mazzanti Cinzia , Cavani Andrea , Ruvo Menotti , Dinarello Charles A. , Albanesi Cristina , Madonna Stefania
Published: October 2018

IL-36 cytokines, a subgroup of IL-1 family, comprise IL-36α, IL-36β, and IL-36γ agonists, abundantly expressed in psoriatic skin, and IL-36RA and IL-38 antagonists. In psoriatic skin, IL-36 cytokines interfere with keratinocyte cornification programs and induce the release of antimicrobial peptides and chemokines active on neutrophils and Th17 lymphocytes. To date, the role of IL-38 antagonist in psoriasis remains to be defined. Here, we demonstrate that skin and circulating IL-38 levels are reduced in psoriatic patients and in other skin diseases characterized by neutrophilic infiltrate. In psoriasis, the balance of IL-36γ agonist/IL-38 antagonist serum levels is in favor of agonists and is closely associated with disease severity. Interestingly, IL-38 is upregulated by anti-IL-17A biological treatment and positively correlates with the therapeutic efficacy of secukinumab in psoriatic patients. The downregulation of IL-38 expression is strictly related to keratinocyte de-differentiation triggered by the inflammatory cytokines IL-36γ, IL-17, and IL-22. Finally, we demonstrate that administration of recombinant full-length IL-38 counteracts in vitro the biological processes induced by IL-36γ in human keratinocytes and endothelial cells and attenuates in vivo the severity of the psoriasiform phenotype induced by IMQ in mice. Such effects are achieved by restoring the physiological programs of keratinocyte proliferation and differentiation, and reducing the immune cell infiltrates.
Inhibition of mTORC1 by lncRNA H19 via disrupting 4E-BP1/Raptor interaction in pituitary tumours
Authors: Wu Ze Rui , Yan Lichong , Liu Yan Ting , Cao Lei , Guo Yu Hang , Zhang Yong , Yao Hong , Cai Lin , Shang Han Bing , Rui Wei Wei , Yang Gang , Zhang Xiao Biao , Tang Hao , Wang Yu , Huang Jin Yan , Wei Yong Xu , Zhao Wei Guo , Su Bing , Wu Zhe Bao
Published: October 2018

Aberrant expression of long noncoding RNA H19 has been associated with tumour progression, but the underlying molecular tumourigenesis mechanisms remain largely unknown. Here, we report that H19 expression is frequently downregulated in human primary pituitary adenomas and is negatively correlated with tumour progression. Consistently, upregulation of H19 expression inhibits pituitary tumour cell proliferation in vitro and tumour growth in vivo. Importantly, we uncover a function of H19, which controls cell/tumour growth through inhibiting function of mTORC1 but not mTORC2. Mechanistically, we show that H19 could block mTORC1-mediated 4E-BP1 phosphorylation without affecting S6K1 activation. At the molecular level, H19 interacted with 4E-BP1 at the TOS motif and competitively inhibited 4E-BP1 binding to Raptor. Finally, we demonstrate that H19 is more effective than cabergoline treatment in the suppression of pituitary tumours. Together, our study uncovered the role of H19-mTOR-4E-BP1 axis in pituitary tumour growth regulation that may be a potential therapeutic target for human pituitary tumours.
Recognition of host Clr-b by the inhibitory NKR-P1B receptor provides a basis for missing-self recognition
Authors: Balaji Gautham R. , Aguilar Oscar A. , Tanaka Miho , Shingu-Vazquez Miguel A. , Fu Zhihui , Gully Benjamin S. , Lanier Lewis L. , Carlyle James R. , Rossjohn Jamie , Berry Richard
Published: October 2018

The interaction between natural killer (NK) cell inhibitory receptors and their cognate ligands constitutes a key mechanism by which healthy tissues are protected from NK cell-mediated lysis. However, self-ligand recognition remains poorly understood within the prototypical NKR-P1 receptor family. Here we report the structure of the inhibitory NKR-P1B receptor bound to its cognate host ligand, Clr-b. NKR-P1B and Clr-b interact via a head-to-head docking mode through an interface that includes a large array of polar interactions. NKR-P1B:Clr-b recognition is extremely sensitive to mutations at the heterodimeric interface, with most mutations severely impacting both Clr-b binding and NKR-P1B receptor function to implicate a low affinity interaction. Within the structure, two NKR-P1B:Clr-b complexes are cross-linked by a non-classic NKR-P1B homodimer, and the disruption of homodimer formation abrogates Clr-b recognition. These data provide an insight into a fundamental missing-self recognition system and suggest an avidity-based mechanism underpins NKR-P1B receptor function.
Potassium channel-based optogenetic silencing
Authors: Bernal Sierra Yinth Andrea , Rost Benjamin R. , Pofahl Martin , Fernandes António Miguel , Kopton Ramona A. , Moser Sylvain , Holtkamp Dominik , Masala Nicola , Beed Prateep , Tukker John J. , Oldani Silvia , Bönigk Wolfgang , Kohl Peter , Baier Herwig , Schneider-Warme Franziska , Hegemann Peter , Beck Heinz , Seifert Reinhard , Schmitz Dietmar
Published: October 2018

Optogenetics enables manipulation of biological processes with light at high spatio-temporal resolution to control the behavior of cells, networks, or even whole animals. In contrast to the performance of excitatory rhodopsins, the effectiveness of inhibitory optogenetic tools is still insufficient. Here we report a two-component optical silencer system comprising photoactivated adenylyl cyclases (PACs) and the small cyclic nucleotide-gated potassium channel SthK. Activation of this ‘PAC-K’ silencer by brief pulses of low-intensity blue light causes robust and reversible silencing of cardiomyocyte excitation and neuronal firing. In vivo expression of PAC-K in mouse and zebrafish neurons is well tolerated, where blue light inhibits neuronal activity and blocks motor responses. In combination with red-light absorbing channelrhodopsins, the distinct action spectra of PACs allow independent bimodal control of neuronal activity. PAC-K represents a reliable optogenetic silencer with intrinsic amplification for sustained potassium-mediated hyperpolarization, conferring high operational light sensitivity to the cells of interest.
Estimating the effect size of surgery to improve walking in children with cerebral palsy from retrospective observational clinical data
Authors: Rajagopal Apoorva , Kidziński Łukasz , McGlaughlin Alec S. , Hicks Jennifer L. , Delp Scott L. , Schwartz Michael H.
Published: October 2018

Single-event multilevel surgery (SEMLS) is a standard treatment approach aimed at improving gait for patients with cerebral palsy, but the effect of this approach compared to natural progression without surgical intervention is unclear. In this study, we used retrospective patient history, physical exam, and three-dimensional gait analysis data from 2,333 limbs to build regression models estimating the effect of SEMLS on gait, while controlling for expected natural progression. Post-hoc classifications using the regression model results identified which limbs would exhibit gait within two standard deviations of typical gait at the follow-up visit with or without a SEMLS with 73% and 77% accuracy, respectively. Using these models, we found that, while surgery was expected to have a positive effect on 93% of limbs compared to natural progression, in only 37% of limbs was this expected effect a clinically meaningful improvement. We identified 26% of the non-surgically treated limbs that may have shown a clinically meaningful improvement in gait had they received surgery. Our models suggest that pre-operative physical therapy focused on improving biomechanical characteristics, such as walking speed and strength, may improve likelihood of positive surgical outcomes. These models are shared with the community to use as an evaluation tool when considering whether or not a patient should undergo a SEMLS.
Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study
Authors: Kvaløy Kirsti , Page Christian Magnus , Holmen Turid Lingaas
Published: October 2018

Knowledge of epigenetically regulated biomarkers linked to obesity development is still scarce. Improving molecular understanding of the involved factors and pathways would improve obesity phenotype characterization and reveal potentially relevant targets for obesity intervention. The Illumina Infinium HumanMethylation450 BeadChip was used in a leucocyte epigenome-wide association study (EWAS) to quantify differential DNA methylation in 60 lean compared with 60 obese young women. Replication was done in monozygotic twins discordant for obesity. At adolescence and adulthood, the two weight groups differed significantly in obesity-related traits and metabolic risk factors. Differential hypomethylation was overrepresented in obese compared to lean women. In the adjusted model, the EWAS revealed 10 differentially methylated CpG sites linked to 8 gene loci – COX6A1P2/FGD2, SBNO2, TEX41, RPS6KA2, IGHE/IGHG1/IGHD, DMAP1, SOCS3, and SETBP1– and an enhancer locus at chromosome 2 (2p25.1). The sites linked to TEX41, IGHE/IGHG1/IGHD, DMAP1, and SETBP1 were novel findings, while COX6A1P/FGD2, SBNO2, RPS6KA2, and SOCS3 had been identified previously with concordant direction of effects. RPS6KA2, DMAP1, and SETBP1 were replicated in the BMI-discordant monozygotic twin cohort using the FDR of 5%.
Roads do not increase carrion use by a vertebrate scavenging community
Authors: Hill Jacob E. , DeVault Travis L. , Beasley James C. , Rhodes Olin E. , Belant Jerrold L.
Published: October 2018

Wildlife-vehicle collisions introduce a considerable amount of carrion into the environment, but scavenger use of this resource has not been extensively investigated. Scavengers may use roads for reliable foraging opportunities, but might also use roads for other purposes and encounter carrion opportunistically. We examined scavenging of carrion along linear features by placing 52 rabbit carcasses in each of three treatments in forested habitat during winter (Dec 2016-Mar 2017) in South Carolina, USA: roads, power line clearings (linear feature with fewer carcasses than roads due to lack of road kill), and forest interior. We used motion-activated cameras to compare arrival times and presence of vertebrate scavengers among treatments. There was no difference in proportion of carcasses scavenged or scavenger arrival time across treatments. No species arrived at roads quicker than other treatments. Turkey vultures (Cathartes aura) and coyotes (Canis latrans) scavenged equally across treatments, whereas gray foxes (Urocyon cinereoargenteus) scavenged along roads and power lines, but not in forests. We suggest that scavenger use of carrion near roads at this location during winter relates to factors other than carrion availability. Because some scavengers readily consumed carrion on roads, this resource has the potential to influence the ecology of these species.
Dairy calves’ personality traits predict social proximity and response to an emotional challenge
Authors: Lecorps Benjamin , Kappel Sarah , Weary Daniel M. , von Keyserlingk Marina A. G.
Published: October 2018

The assessment of individual traits requires that tests are reliable (i.e. consistency over time) and externally valid, meaning that they predict future responses in similar contexts (i.e. convergent validity) but do not predict responses to unrelated situations (i.e. discriminant validity). The aim of this study was to determine if dairy calf personality traits (Fearfulness, Sociability and Pessimism), derived from behaviours expressed in standardized tests, predict individuals’ responses in related situations. The first experiment tested if the trait ‘Sociability’ was related to the expression of social behaviour in the home-pen, with calves assigned individual proximity scores (based on proximity to other calves) while they were in their home-pen at approximately 113 and 118 d of age. The second experiment aimed at exploring whether traits ‘Fearfulness’ and ‘Pessimism’ were related to the calves’ emotional response to transportation. All calves were subjected to two 10-min transportation challenges done on two consecutive days. Emotional response was assessed using the maximum eye temperature (measured using infrared thermography) and the number of vocalizations emitted. Social proximity scores (Experiment 1), vocalizations emitted and maximum eye temperature after loading (Experiment 2) were consistent over time. In addition, the results showed good convergent validity with calves scoring higher in Sociability also having higher proximity scores in the home-pen, and animals scoring higher in Fearfulness and Pessimism showing a more intense emotional response to transportation. The results also showed good discriminant validity, as neither Fearfulness nor Pessimism were associated with the expression of social behaviours (Experiment 1) and Sociability was not associated with the animal’s emotional response to transportation (Experiment 2). We conclude that the methodology used to measure personality traits shows good reliability and external validity.
Stent graft coverage of dual-stent strategy in the management of abdominal aortic aneurysms
Authors: Ding Yuan , Zhongyou Li , Wentao Jiang , Yinci Zhang , Zhenze Wang , Yu Chen
Published: October 2018

Treating an abdominal aortic aneurysm (AAA) with a stent graft (SG) and a multilayer stent (MS) is a key technology in isolating flow fields. Clinically, dual stents (an SG in the proximal and an MS in the distal of AAA) are used for treatment of AAA, but only a few studies have examined the relationship between SG coverage and treatment effects. Through numerical simulation of the hemodynamics after SG and MS implantation, the SG coverage and position were simulated at 0% (0 mm), 25% (13.75 mm), 50% (27.5 mm), and 75% (41.25 mm). With increasing SG coverage, the pressure on the aneurysm sac wall and the flow of branch vessels gradually decreased, and the lower wall shear stress (WSS) gradually increased. The changes in pressure, lower WSS, and the mass flow rate of the branch vessels did not change significantly. The coverage of the SG has a nonsignificant effect on hemodynamics in the treatment of AAA; the implantation position need not be very precise. This research can provide theoretic support for clinicians’ decision-making.
Impact of Stokes Shift on the Performance of Near-Infrared Harvesting Transparent Luminescent Solar Concentrators
Authors: Yang Chenchen , Zhang Jun , Peng Wei-Tao , Sheng Wei , Liu Dianyi , Kuttipillai Padmanaban S. , Young Margaret , Donahue Matthew R. , Levine Benjamin G. , Borhan Babak , Lunt Richard R.
Published: October 2018

Visibly transparent luminescent solar concentrators (TLSC) have the potential to turn existing infrastructures into net-zero-energy buildings. However, the reabsorption loss currently limits the device performance and scalability. This loss is typically defined by the Stokes shift between the absorption and emission spectra of luminophores. In this work, the Stokes shifts (SS) of near-infrared selective-harvesting cyanines are altered by substitution of the central methine carbon with dialkylamines. We demonstrate varying SS with values over 80 nm and ideal infrared-visible absorption cutoffs. The corresponding TLSC with such modification shows a power conversion efficiency (PCE) of 0.4% for a >25 cm2 device area with excellent visible transparency >80% and up to 0.6% PCE over smaller areas. However, experiments and simulations show that it is not the Stokes shift that is critical, but the total degree of overlap that depends on the shape of the absorption tails. We show with a series of SS-modulated cyanine dyes that the SS is not necessarily correlated to improvements in performance or scalability. Accordingly, we define a new parameter, the overlap integral, to sensitively correlate reabsorption losses in any LSC. In deriving this parameter, new approaches to improve the scalability and performance are discussed to fully optimize TLSC designs to enhance commercialization efforts.
Enhanced microbubble contrast agent oscillation following 250 kHz insonation
Authors: Ilovitsh Tali , Ilovitsh Asaf , Foiret Josquin , Caskey Charles F. , Kusunose Jiro , Fite Brett Z. , Zhang Hua , Mahakian Lisa M. , Tam Sarah , Butts-Pauly Kim , Qin Shengping , Ferrara Katherine W.
Published: October 2018

Microbubble contrast agents are widely used in ultrasound imaging and therapy, typically with transmission center frequencies in the MHz range. Currently, an ultrasound center frequency near 250 kHz is proposed for clinical trials in which ultrasound combined with microbubble contrast agents is applied to open the blood brain barrier, since at this low frequency focusing through the human skull to a predetermined location can be performed with reduced distortion and attenuation compared to higher frequencies. However, the microbubble vibrational response has not yet been carefully evaluated at this low frequency (an order of magnitude below the resonance frequency of these contrast agents). In the past, it was assumed that encapsulated microbubble expansion is maximized near the resonance frequency and monotonically decreases with decreasing frequency. Our results indicated that microbubble expansion was enhanced for 250 kHz transmission as compared with the 1 MHz center frequency. Following 250 kHz insonation, microbubble expansion increased nonlinearly with increasing ultrasonic pressure, and was accurately predicted by either the modified Rayleigh–Plesset equation for a clean bubble or the Marmottant model of a lipid-shelled microbubble. The expansion ratio reached 30-fold with 250 kHz at a peak negative pressure of 400 kPa, as compared to a measured expansion ratio of 1.6 fold for 1 MHz transmission at a similar peak negative pressure. Further, the range of peak negative pressure yielding stable cavitation in vitro was narrow (~100 kPa) for the 250 kHz transmission frequency. Blood brain barrier opening using in vivo transcranial ultrasound in mice followed the same trend as the in vitro experiments, and the pressure range for safe and effective treatment was 75–150 kPa. For pressures above 150 kPa, inertial cavitation and hemorrhage occurred. Therefore, we conclude that (1) at this low frequency, and for the large oscillations, lipid-shelled microbubbles can be approximately modeled as clean gas microbubbles and (2) the development of safe and successful protocols for therapeutic delivery to the brain utilizing 250 kHz or a similar center frequency requires consideration of the narrow pressure window between stable and inertial cavitation.
Diversity and convergence of mechanisms involved in pyrethroid resistance in the stored grain weevils, Sitophilus spp.
Authors: Haddi Khalid , Valbon Wilson R. , Viteri Jumbo Luis O. , de Oliveira Luiz O. , Guedes Raul N. C. , Oliveira Eugenio E.
Published: October 2018

Target-site mutations and changes in insect metabolism or behavior are common mechanisms in insecticide-resistant insects. The co-occurrence of such mechanisms in a pest strain is a prominent threat to their management, particularly when alternative compounds are scarce. Pyrethroid resistance among stored grain weevils (i.e., Sitophilus spp.) is an example of a long-standing concern, for which reports of resistance generally focus on a single mechanism in a single species. Here, we investigated pyrethroid resistance in maize and rice weevils (i.e., Sitophilus zeamais and S. oryzae), exploring potential knockdown resistance (kdr) mutations in their sodium channels (primary site for pyrethroid actions) and potential changes in their detoxification and walking processes. Resistance in pyrethroid-resistant rice weevils was associated with the combination of a kdr mutation (L1014F) and increases in walking and detoxification activities, while another kdr mutation (T929I) combined with increases in walking activity were the primary pyrethroid resistance mechanisms in maize weevils. Our results suggest that the selection of pyrethroid-resistant individuals in these weevil species may result from multiple and differential mechanisms because the L1014F mutation was only detected in Latin American rice weevils (e.g., Brazil, Argentina and Uruguay), not in Australian and Turkish rice weevils or Brazilian maize weevils.
Receptor-Ligand Interaction Mediates Targeting of Endothelial Colony Forming Cell-derived Exosomes to the Kidney after Ischemic Injury
Authors: Viñas Jose L. , Spence Matthew , Gutsol Alex , Knoll William , Burger Dylan , Zimpelmann Joseph , Allan David S. , Burns Kevin D.
Published: October 2018

Endothelial colony forming cell (ECFC)-derived exosomes protect mice against ischemic kidney injury, via transfer of microRNA-(miR)-486-5p. Mechanisms mediating exosome recruitment to tissues are unclear. We hypothesized that ECFC exosomes target ischemic kidneys, involving interaction between exosomal CXC chemokine receptor type 4 (CXCR4) and stromal cell-derived factor (SDF)-1α. Ischemia-reperfusion was induced in mice by bilateral renal vascular clamp, with intravenous infusion of exosomes at reperfusion. Optical imaging determined exosome biodistribution, and miR-486-5p was measured by real-time PCR. Human umbilical vein endothelial cells (HUVECs) were cultured to study the CXCR4/SDF-1α interaction. Targeting of administered exosomes to ischemic kidneys was detected 30 min and 4 hrs after reperfusion. Exosomes increased miR-486-5p levels only in kidneys, within proximal tubules, glomeruli, and endothelial cells. Uptake of fluorescently-labeled exosomes into HUVECs, and exosomal transfer of miR-486-5p were enhanced by hypoxia, effects blocked by neutralizing antibody to SDF-1α or by the CXCR4 inhibitor plerixafor. Infusion of ECFC exosomes prevented ischemic kidney injury in vivo, an effect that was not observed when exosomes were pre-incubated with plerixafor. These data indicate that ECFC exosomes selectively target the kidneys after ischemic injury, with rapid cellular transfer of miR486-5p. Targeting of exosomes may involve interaction of CXCR4 with endothelial cell SDF-1α.
Aberrant DNA methylation of Tgfb1 in diabetic kidney mesangial cells
Authors: Oba Shigeyoshi , Ayuzawa Nobuhiro , Nishimoto Mitsuhiro , Kawarazaki Wakako , Ueda Kohei , Hirohama Daigoro , Kawakami-Mori Fumiko , Shimosawa Tatsuo , Marumo Takeshi , Fujita Toshiro
Published: October 2018

Epigenetic modulation may underlie the progression of diabetic nephropathy (DN). Involvement of TGFB1 in mesangial fibrosis of DN led us to hypothesize that Tgfb1 DNA demethylation contributes to progression of DN. In primary mesangial cells from diabetic (db/db) mouse kidneys, demethylation of Tgfb1 DNA and upregulation of Tgfb1 mRNA progressed simultaneously. USF1 binding site in Tgfb1 promoter region were demethylated, and binding of USF1 increased, with decreased binding of DNMT1 in db/db compared with control. Given downregulation of Tgfb1 expression by folic acid, antioxidant Tempol reversed DNA demethylation, with increased and decreased recruitment of DNMT1 and USF1 to the promoter, resulting in decreased Tgfb1 expression in db/db mice. Addition of H2O2 to mesangial cells induced DNA demethylation and upregulated Tgfb1 expression. Finally, Tempol attenuated mesangial fibrosis in db/db mice. We conclude that aberrant DNA methylation of Tgfb1 due to ROS overproduction play a key to mesangial fibrosis during DN progression.
Characterizing directed functional pathways in the visual system by multivariate nonlinear coherence of fMRI data
Authors: Goelman Gadi , Dan Rotem , Keadan Tarek
Published: October 2018

A multivariate measure of directed functional connectivity is used with resting-state fMRI data of 40 healthy subjects to identify directed pathways of signal progression in the human visual system. The method utilizes 4-nodes networks of mutual interacted BOLD signals to obtains their temporal hierarchy and functional connectivity. Patterns of signal progression were defined at frequency windows by appealing to a hierarchy based upon phase differences, and their significance was assessed by permutation testing. Assuming consistent phase relationship between neuronal and fMRI signals and unidirectional coupling, we were able to characterize directed pathways in the visual system. The ventral and dorsal systems were found to have different functional organizations. The dorsal system, particularly of the left hemisphere, had numerous feedforward pathways connecting the striate and extrastriate cortices with non-visual regions. The ventral system had fewer pathways primarily of two types: (1) feedback pathways initiated in the fusiform gyrus that were either confined to the striate and the extrastriate cortices or connected to the temporal cortex, (2) feedforward pathways initiated in V2, excluded the striate cortex, and connected to non-visual regions. The multivariate measure demonstrated higher specificity than bivariate (pairwise) measure. The analysis can be applied to other neuroimaging and electrophysiological data.