bluuebunny/crossref_metadata_2025 huggingface dataset:
A Framework for Understanding Consumer Choices for Others
Authors: Liu Peggy J , Dallas Steven K , Fitzsimons Gavan J
Published: March 2019

Although most research on consumers’ choices, and resulting insights, have focused on choices that consumers make solely for themselves, consumers often make choices for others, and there is a growing literature examining such choices. Theoretically, how can this growing literature be integrated, and what gaps remain? Practically, why should marketers, consumers, and policy makers care when choices are made for others, and what should they do differently? A 2 × 2 framework of consumers’ choices for others addresses these questions. This framework has two fundamental dimensions: the chooser’s social focus (relationship vs. recipient oriented) and the chooser’s consideration of consumption preferences (highlight the recipient’s preferences vs. balance the recipient’s preferences with the chooser’s preferences). These dimensions generate four cells that represent prototypical choosing-for-others contexts: gift-giving (relationship focus, highlighting recipient’s preferences), joint consumption (relationship focus, balancing recipient’s and chooser’s preferences), everyday favors/pick-ups (recipient focus, highlighting recipient’s preferences), and caregiving (recipient focus, balancing recipient’s and chooser’s preferences). This framework captures most choosing-for-others situations, and each cell involves a distinct profile of motives, ultimately affecting choices. This framework integrates the choosing-for-others literature, which we hope will guide future research, and it also offers practical implications for marketers, consumers, and policy makers.
What’s Wrong with Behrami and Saramati? Revisiting the Dichotomy between UN Peacekeeping and UN-authorized Operations in Terms of Attribution
Authors: Okada Yohei
Published: March 2019

The Behrami and Saramati decision of the European Court of Human Rights (ECtHR) has invited severe censure for discarding the well-established dichotomy between UN peacekeeping and UN-authorized operations, and applying the ultimate authority and control test instead of the effective control test for the purpose of attribution in the context of the UN-authorized operation in Kosovo. Harsh criticism notwithstanding, in Serdar Mohammed and Kontic, the domestic courts in the UK have recently followed the Behrami and Saramati approach. In Kontic, nearly 10 years after the Behrami and Saramati decision, the court found that the approach taken by the ECtHR was ‘persuasive authority of the very weightiest kind’. Therefore, it is high time for Behrami and Saramati to be revisited. This study argues that the ECtHR did apply the effective control test along with the ultimate authority and control test in Behrami and Saramati, and that the UK courts aligned themselves with this approach. The Behrami and Saramati decision was not fundamentally wrong as a matter of interpretation and the conclusion reached by the ECtHR that the misconduct was not attributable to the respondent states was not manifestly absurd. Nevertheless, the decision was not without deficiency because it failed to take full account of the delicate equilibrium that the effective control test seeks. The present study aims to precisely identify what was wrong with the decision.
Effects of Load Carriage and Step Length Manipulation on Achilles Tendon and Knee Loads
Authors: Willy Richard W , DeVita Paul , Meardon Stacey A , Baggaley Michael , Womble Christopher C , Willson John D
Published: March 2019

Introduction

Longer steps with load carriage is common in shorter Soldiers when matching pace with taller Soldiers whereas shorter steps are hypothesized to reduce risk of injury with load carriage. The effects of load carriage with and without step length manipulation on loading patterns of three commonly injured structures were determined: Achilles tendon, patellofemoral joint (PFJ) and medial tibiofemoral joint (mTFJ).

Materials and Methods

ROTC Cadets (n = 16; 20.1 years ± 2.5) walked with and without load carriage (20-kg). Cadets then altered preferred step lengths ±7.5% with load carriage. Achilles tendon, PFJ and mTFJ loads were estimated via musculoskeletal modeling.

Results

Large increases in peak Achilles tendon load (p < 0.001, d = 1.93), Achilles tendon impulse per 1-km (p < 0.001, d = 0.91), peak mTFJ load (p < 0.001, d = 1.33), and mTFJ impulse per 1-km (p < 0.001, d = 1.49) were noted with load carriage while moderate increases were observed for the PFJ (peak: p < 0.001, d = 0.69; impulse per 1-km: p < 0.001, d = 0.69). Shortened steps with load carriage only reduced peak Achilles tendon load (p < 0.001, d = –0.44) but did not reduce Achilles impulse per km due to the resulting extra steps and also did not reduce peak or cumulative PFJ and mTFJ loads (p > 0.05). Longer steps with load carriage increased PFJ loads the most (p < 0.001, d = 0.68–0.75) with moderate increases in mTFJ forces (p < 0.001, d = 0.48–0.63) with no changes in Achilles tendon loads (p = 0.11–0.20).

Conclusion

A preferred step length is the safest strategy when walking with load carriage. Taking a shorter step is not an effective strategy to reduce loading on the Achilles tendon, PFJ, and mTFJ.
A high-fidelity realization of the Euclid code comparison N-body simulation with Abacus
Authors: Garrison Lehman H , Eisenstein Daniel J , Pinto Philip A
Published: March 2019

We present a high-fidelity realization of the cosmological N-body simulation from the Schneider et al. code comparison project. The simulation was performed with our AbacusN-body code, which offers high-force accuracy, high performance, and minimal particle integration errors. The simulation consists of 20483 particles in a $500\ h^{-1}\, \mathrm{Mpc}$ box for a particle mass of $1.2\times 10^9\ h^{-1}\, \mathrm{M}_\odot$ with $10\ h^{-1}\, \mathrm{kpc}$ spline softening. Abacus executed 1052 global time-steps to z = 0 in 107 h on one dual-Xeon, dual-GPU node, for a mean rate of 23 million particles per second per step. We find Abacus is in good agreement with Ramses and Pkdgrav3 and less so with Gadget3. We validate our choice of time-step by halving the step size and find sub-percent differences in the power spectrum and 2PCF at nearly all measured scales, with ${\lt }0.3{{\ \rm per\ cent}}$ errors at $k\lt 10\ \mathrm{Mpc}^{-1}\, h$. On large scales, Abacus reproduces linear theory better than 0.01 per cent. Simulation snapshots are available at http://nbody.rc.fas.harvard.edu/public/S2016.
Anomalous outbursts of H 1743-322
Authors: Ghosh Arindam , Chakrabarti Sandip K
Published: March 2019

Using soft (1.5–3 keV) and hard (3–12 keV) photon counts of All Sky Monitor (ASM) in Rossi X-ray Timing Explorer (RXTE) satellite, we have proposed recently that there is a significant time lag between the infall time-scales of two components in the Two-Component Advective Flow paradigm, where a standard slow moving Keplerian disc is surrounded by a fast moving halo. The time lag is clearly due to the difference in viscosity in the flow components and the size of the Keplerian disc may be considered to be proportional to this arrival time lag. In this paper, using RXTE/ASM (1.5–12 keV) data, we examine eight successive outbursts of the low-mass X-ray binary H 1743-322 since 2003 from a new perspective. The day-to-day temporal evolution of a dynamic photon index, Θ, as well as its cross-correlation with the soft and hard energy fluxes show that the aforesaid time lag was the longest during the brightest outburst of 2003 – thereby indicating its largest Keplerian disc. The disc size diminished thereafter during subsequent weaker outbursts. Moreover, Θ decides spectral transitions of any outburst. We show from the behaviour of Θ alone that the outburst of October 2008 was anomalous while the outburst of 2003 was twin (anomalous + normal). In fact, each normal outburst was either preceded or followed by an otherwise premature outburst showing different degrees of anomaly. This makes H 1743-322 an enigmatic source and a subject of further study.
The MUSE Ultra Deep Field (MUDF) – I. Discovery of a group of Lyα nebulae associated with a bright z ≈ 3.23 quasar pair
Authors: Lusso E , Fumagalli M , Fossati M , Mackenzie R , Bielby R M , Arrigoni Battaia F , Cantalupo S , Cooke R , Cristiani S , Dayal P , D’Odorico V , Haardt F , Lofthouse E , Morris S , Peroux C , Prichard L , Rafelski M , Simcoe R , Swinbank A M , Theuns T
Published: March 2019

We present first results from Multi Unit Spectroscopic Explorer (MUSE) observations at the Very Large Telescope in the MUSE Ultra Deep Field (MUDF), a ≈1.2 × 1.4 arcmin2 region for which we are collecting ≈200 hours of integral field spectroscopy. The ≈40-h observation completed to date reveals the presence of a group of three Lyα nebulae associated with a bright quasar pair at $z$ ≃ 3.23 with projected separation of ${\approx } 500\rm ~kpc$. Two of the nebulae are physically associated with the quasars which are likely powering the Lyα emission, and extend for ${\gtrsim } 100~\rm kpc$ at a surface brightness level of ≈6 × 10−19 $\rm erg\,s^{-1}\,cm^{-2}\,arcsec^{-2}$. A third smaller (≈35 kpc) nebula lies at a velocity offset of ≈1550 km s−1. Despite their clustered nature, the two large nebulae have properties similar to those observed in isolated quasars and exhibit no sharp decline in flux at the current depth, suggesting an even more extended distribution of gas around the quasars. We interpret the shape and the alignment of the two brighter nebulae as suggestive of the presence of an extended structure connecting the two quasar host galaxies, as seen for massive galaxies forming within gas-rich filaments in cosmological simulations.
A Qualitative Examination of Stay Quit Coach, A Mobile Application for Veteran Smokers With Posttraumatic Stress Disorder
Authors: Herbst Ellen , McCaslin Shannon E , Hassanbeigi Daryani Shahrzad , Laird Kelsey T , Hopkins Lindsey B , Pennington David , Kuhn Eric
Published: March 2019

Introduction

Smoking is a lethal public health problem that is common in US military veterans, particularly those with posttraumatic stress disorder (PTSD). Mobile applications (apps) to promote smoking cessation are a scalable and low-cost approach that may facilitate treatment engagement.

Methods

This qualitative study examined the acceptability, user experience, and perceptions of a smoking cessation app, Stay Quit Coach (SQC), when incorporated into evidence-based smoking cessation treatment. US military veterans with PTSD who smoked at least five cigarettes per day for 15 of the past 30 days and stated an interested in cessation were eligible to participate. Participants’ baseline comfort levels with mobile technology was measured using the Perceptions of Mobile Phone Interventions Questionnaire–Patient version (PMPIQ-P). At treatment end, semi-structured qualitative interviews were conducted.

Results

Twenty participants were enrolled and 17 (85.0%) participated in the qualitative interview at treatment end. PMPIQ-P scores at baseline ranged from 4.97 to 5.25 (SDs = 0.73–1.04), reflecting moderately high comfort with mobile technology among participants. Qualitative analyses indicated that most participants: (1) endorsed mobile technology as an appealing format for smoking cessation treatment, due to convenience and instantaneous access; and (2) expressed highest perceived helpfulness for interactive app features. Recommendations to improve SQC clustered into four thematic areas: (1) increasing personalization, (2) including more self-tracking features, (3) increasing visual cues, and (4) sharing progress with peers.

Conclusions

SQC was perceived as an acceptable and useful tool to support smoking cessation in a sample of veteran smokers with PTSD. Qualitative data provided valuable insights that can inform the continued development of SQC and other apps for smoking cessation.

Implications

Given the high lethality associated with cigarette smoking, it is crucial to identify scalable, low-risk strategies to promote smoking cessation, particularly in high-risk populations. Mobile technology is a promising approach that can be used to augment evidence-based smoking cessation treatment. Results of this qualitative study support the use of the SQC mobile app when incorporated into evidence-based smoking cessation treatment for veterans with PTSD and provide future directions for refinement of the SQC app. These findings also highlight the importance of using a patient-centered approach in designing apps intended for a clinical population.
Prognostic Factors in Complex Regional Pain Syndrome Type 1 Occurring in the Korean Army
Authors: Lee Won Joon , Jung Cheol Hee , Hwang Jae Yeon , Seong Su-Jeong , Han Chang Hwan , Park Jin Woo , Jang Joon Hwan , Lee Dasom , Kang Do-Hyung
Published: March 2019

Objectives

In Korea, patients diagnosed with complex regional pain syndrome (CRPS) in the army are typically discharged from the army; however, the course of the disease after discharge is not known. The purpose of this study was to investigate the course of CRPS that occurred in the army and to identify the influences of various clinical and psychosocial factors immediately before discharge on the disease course.

Methods

Clinical profiles and psychosocial status were collected from the medical records of 16 patients with CRPS type 1 who were discharged during the period between March 2017 and April 2018. The degree of improvement after discharge was assessed by follow-up evaluation through telephone contact. Cox proportional hazards regression was performed to identify clinical and psychosocial predictors for the rate of recovery.

Results

The median time to recovery after discharge was 39 weeks (95% confidence interval [CI] = 8.8–69.2 weeks). The sole predictor for time to recovery after discharge was the time period from the onset of pain to discharge. Each one-week increase in the duration of pain experienced in the military was associated with a 18.2% (95% CI = 5.3%–29.5%) reduction in the rate of recovery after discharge (P = 0.007).

Conclusions

Patients who experienced a short period of pain in the military demonstrated a relatively good prognosis after discharge. This may show how prolonged pain in the army could affect the experience of pain from a social point of view, in that it shows the disease course after a change in the social environment.
Observational evidence of the seasonal and demographic variation in experienced temperature from 77 743 UK Biobank participants
Authors: Kennard H R , Huebner G M , Shipworth D
Published: March 2019

Background

Exposure to cold is known to be associated with severe health impacts. The primary epidemiological evidence for this is the seasonal variation in mortality. However, there is a paucity of directly measured data for personal cold temperature exposure. This paper develops the concept of experienced temperature, and reports how it varies with season, demographics and housing factors.

Methods

This study uses data from 77 743 UK Biobank participants. A novel method to directly measure participant’s exposure to low temperatures using a thermistor in a wrist-worn activity monitor is described. These readings are combined with demographic and housing factor variables in a multiple regression model to understand underlying relationships.

Results

The study reveals a significant difference in experienced temperature of ~1.8°C between the periods of coldest and hottest external temperature. A number of demographic differences were also observed—such as people of Chinese ethnic background experiencing 0.65°C lower temperatures than other groups.

Conclusions

This paper presents primary evidence for a seasonal variation in experienced temperature. This variation likely contributes to cold related mortality and morbidity. It is hypothesized that this relationship would be less strong in countries which suffer fewer impacts of cold winter temperatures.
CYTOGENETIC BIODOSIMETRY OF ACCIDENTAL EXPOSURES IN THE LONG TERMS AFTER IRRADIATION
Authors: Nugis V Yu , Kozlova M G , Nadejina N M , Galstyan I A , Nikitina V A , Khvostunov I K , Golub E V
Published: March 2019

The group of radiation victims who had received radiation injures similar to those of Chernobyl accident victims was evaluated in terms of retrospective cytogenetic biodosimetry in the long term period of from 17 y up to 50 y after irradiation. Based on the existing results of the long-term cytogenetic examination of the victims injured after the Chernobyl accident, an original method was developed. This method of retrospective dose recovery was based on the use of a special computer program, the time elapsed after irradiation and the frequency of atypical chromosomes. Both patient groups were examined using conventional cytogenetic analysis. The new method of a retrospective biodosimetry was tested on the non-Chernobyl group. As a result the multiple regression equations which included frequency atypical chromosomes produced better results because the majority of the estimates of the retrospective doses fell into the 95%-prediction intervals for the reference group of the Chernobyl victims.
Diabloroter bolti, a short-bodied recumbirostran ‘microsaur’ from the Francis Creek Shale, Mazon Creek, Illinois
Authors: Mann Arjan , Maddin Hillary C
Published: March 2019

The Carboniferous (Pennsylvanian; 309–307 Mya) ‘Mazon Creek’ Lagerstätte produces some of the earliest tetrapod fossils of major Palaeozoic lineages. Previously, the Mazon Creek record of ‘microsaurs’ was known from a single specimen. However, the lack of key anatomy, such as the skull, precluded a confident taxonomic assignment, thus only a suggested affinity to the microbrachimorph ‘microsaur’ Hyloplesion was determined. Recently several new tetrapod specimens collected from Mazon Creek have come to light, of which some have recumbirostran ‘microsaur’ affinity. Here we describe a new genus and species of short-bodied recumbirostran, Diabloroter bolti, on the basis of a unique combination of autapomorphies. Both parsimony and Bayesian phylogenetic methods recover the new taxon in the Brachystelechidae clade, as sister to a clade including Carrolla and Batropetes. We determine Diabloroter to be the earliest known member of Brachytelechidae and thus establishing a Carboniferous origin of the family. We also provide an updated diagnosis for Brachystelechidae. Finally, we comment on the evolutionary trends in the clade, including dental adaptations for a proposed algivorous diet in derived clade members.
Mangrove dynamics and blue carbon sequestration
Authors: Rogers Kerrylee , Saintilan Neil , Mazumder Debashish , Kelleway Jeffrey J.
Published: March 2019

We monitored coastal wetland vertical accretion, elevation gain and surface carbon (C) at Homebush Bay, Australia over 18 years (2000–2017) in three settings initially characterized by saltmarsh, mixed saltmarsh–mangrove ecotone and mangrove-dominated zones. During this time, the saltmarsh transitioned to mixed saltmarsh–mangrove ecotone, and the mixed saltmarsh–mangrove ecotone transitioned to mangrove, consistent with vegetation transitions observed across the east Australian continent in recent decades. In spite of mangrove recruitment and thickening in the former saltmarsh zone, and the dominance of mangrove root material as a contributing C source, the rate of C accumulation in the former saltmarsh zone did not change over the study period, and there was no significant increase in surface elevation. This contrasted with the response of sites with a longer history of mangrove colonization, which showed strong accretion and C accumulation over the period. The result suggests that the C accumulation and surface elevation gains made as a result of mangrove colonization may not be observable over initial decades, but will be significant in the longer term as forests reach maturity.
Dispersal syndromes can impact ecosystem functioning in spatially structured freshwater populations
Authors: Little Chelsea J. , Fronhofer Emanuel A. , Altermatt Florian
Published: March 2019

Dispersal can strongly influence ecological and evolutionary dynamics. Besides the direct contribution of dispersal to population dynamics, dispersers often differ in their phenotypic attributes from non-dispersers, which leads to dispersal syndromes. The consequences of such dispersal syndromes have been widely explored at the population and community level; however, to date, ecosystem-level effects remain unclear. Here, we examine whether dispersing and resident individuals of two different aquatic keystone invertebrate species have different contributions to detrital processing, a key function in freshwater ecosystems. Using experimental two-patch systems, we found no difference in leaf consumption rates with dispersal status of the common native species
Gammarus fossarum
. In
Dikerogammarus villosus
, however, a Ponto-Caspian species now expanding throughout Europe, dispersers consumed leaf litter at roughly three times the rate of non-dispersers. Furthermore, this put the contribution of dispersing
D. villosus
to leaf litter processing on par with native
G. fossarum,
after adjusting for differences in organismal size. Given that leaf litter decomposition is a key function in aquatic ecosystems, and the rapid species turnover in freshwater habitats with range expansions of non-native species, this finding suggests that dispersal syndromes may have important consequences for ecosystem functioning.
Limits to the rate of information transmission through the MAPK pathway
Authors: Grabowski Frederic , Czyż Paweł , Kochańczyk Marek , Lipniacki Tomasz
Published: March 2019

Two important signalling pathways of NF-κB and ERK transmit merely 1 bit of information about the level of extracellular stimulation. It is thus unclear how such systems can coordinate complex cell responses to external cues. We analyse information transmission in the MAPK/ERK pathway that converts both constant and pulsatile EGF stimulation into pulses of ERK activity. Based on an experimentally verified computational model, we demonstrate that, when input consists of sequences of EGF pulses, transmitted information increases nearly linearly with time. Thus, pulse-interval transcoding allows more information to be relayed than the amplitude–amplitude transcoding considered previously for the ERK and NF-κB pathways. Moreover, the information channel capacity C, or simply bitrate, is not limited by the bandwidth
B
= 1/
τ
, where
τ
≈ 1 h is the relaxation time. Specifically, when the input is provided in the form of sequences of short binary EGF pulses separated by intervals that are multiples of
τ
/
n
(but not shorter than
τ
), then for
n
= 2,
C
≈ 1.39 bit h
−1
; and for
n
= 4,
C
≈ 1.86 bit h
−1
. The capability to respond to random sequences of EGF pulses enables cells to propagate spontaneous ERK activity waves across tissue.
Pro-apoptotic and pro-proliferation functions of the JNK pathway of
Drosophila
: roles in cell competition, tumorigenesis and regeneration
Authors: Pinal Noelia , Calleja Manuel , Morata Ginés
Published: March 2019

The Jun N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family. It appears to be conserved in all animal species where it regulates important physiological functions involved in apoptosis, cell migration, cell proliferation and regeneration. In this review, we focus on the functions of JNK in
Drosophila
imaginal discs, where it has been reported that it can induce both cell death and cell proliferation. We discuss this apparent paradox in the light of recent findings and propose that the pro-apoptotic and the pro-proliferative functions are intrinsic properties of JNK activity. Whether one function or another is predominant depends on the cellular context.
Functional ectodermal organ regeneration as the next generation of organ replacement therapy
Authors: Ikeda Etsuko , Ogawa Miho , Takeo Makoto , Tsuji Takashi
Published: March 2019

In this decade, substantial progress in the fields of developmental biology and stem cell biology has ushered in a new era for three-dimensional organ regenerative therapy. The emergence of novel three-dimensional cell manipulation technologies enables the effective mimicking of embryonic organ germ formation using the fate-determined organ-inductive potential of epithelial and mesenchymal stem cells. This advance shows great potential for the regeneration of functional organs with substitution of complete original function
in situ
. Organoids generated from multipotent stem cells or tissue stem cells via establishment of an organ-forming field can only partially recover original organ function owing to the size limitation; they are considered ‘mini-organs’. Nevertheless, they hold great promise to realize regenerative medicine. In particular, regeneration of a functional salivary gland and an integumentary organ system by orthotopic and heterotopic implantation of organoids clearly points to the future direction of organ regeneration research. In this review, we describe multiple strategies and recent progress in regenerating functional three-dimensional organs, focusing on ectodermal organs, and discuss their potential and future directions to achieve organ replacement therapy as a next-generation regenerative medicine.
How group composition affects cooperation in fixed networks: can psychopathic traits influence group dynamics?
Authors: Testori Martina , Hoyle Rebecca B. , Eisenbarth Hedwig
Published: March 2019

Static networks have been shown to foster cooperation for specific cost–benefit ratios and numbers of connections across a series of interactions. At the same time, psychopathic traits have been discovered to predict defective behaviours in game theory scenarios. This experiment combines these two aspects to investigate how group cooperation can emerge when changing group compositions based on psychopathic traits. We implemented a modified version of the Prisoner’s Dilemma game which has been demonstrated theoretically and empirically to sustain a constant level of cooperation over rounds. A sample of 190 undergraduate students played in small groups where the percentage of psychopathic traits in each group was manipulated. Groups entirely composed of low psychopathic individuals were compared with communities with 50% high and 50% low psychopathic players, to observe the behavioural differences at the group level. Results showed a significant divergence of the mean cooperation of the two conditions, regardless of the small range of participants’ psychopathy scores. Groups with a large density of high psychopathic subjects cooperated significantly less than groups entirely composed of low psychopathic players, confirming our hypothesis that psychopathic traits affect not only individuals’ decisions but also the group behaviour. This experiment highlights how differences in group composition with respect to psychopathic traits can have a significant impact on group dynamics, and it emphasizes the importance of individual characteristics when investigating group behaviours.
Collembola interact with mycorrhizal fungi in modifying oak morphology, C and N incorporation and transcriptomics
Authors: Graf Marcel , Bönn Markus , Feldhahn Lasse , Kurth Florence , Grams Thorsten E. E. , Herrmann Sylvie , Tarkka Mika , Buscot Francois , Scheu Stefan
Published: March 2019

Soil detritivores such as Collembola impact plant growth, tissue nutrient concentration and gene expression. Using a model system with pedunculate oak (Quercus robur) microcuttings that display a typical endogenous rhythmic growth with alternating shoot (SF) and root flushes (RF), we investigated the transcriptomic response of oak with and without mycorrhiza (Piloderma croceum) to the presence of Collembola (Protaphorura armata), and linked it to changes in resource allocation by pulse labelling the plants with13C and15N. Collembola impacted Gene Ontology (GO) terms as well as plant morphology and elemental ratios with the effects varying markedly with developmental phases. During SF Collembola increased GO terms related to primary growth and this was mirrored in increased13C and15N excess in aboveground plant compartments. During RF, Collembola increased GO terms related to plant secondary metabolism and physical fortification. Further, Collembola presence resulted in an increase in plant defence-related GO terms suggesting that Collembola in the rhizosphere prime oak shoots against the attack by fungi or herbivores. Notably, the impact of Collembola on growth, resource allocation and oak gene expression was modified by presence ofP. croceum. The results indicate that oaks clearly react to the presence of Collembola in the rhizosphere and respond in a complex way by changing the expression of genes of both primary and secondary metabolism, and this resulted in concomitant changes in plant morphology and physiology.
Hardy inequalities on metric measure spaces
Authors: Ruzhansky Michael , Verma Daulti
Published: March 2019

In this note, we give several characterizations of weights for two-weight Hardy inequalities to hold on general metric measure spaces possessing polar decompositions. Since there may be no differentiable structure on such spaces, the inequalities are given in the integral form in the spirit of Hardy's original inequality. We give examples obtaining new weighted Hardy inequalities on

R

n

, on homogeneous groups, on hyperbolic spaces and on Cartan–Hadamard manifolds. We note that doubling conditions are not required for our analysis.
Understanding how a falling ball chain can be speeded up by impact onto a surface
Authors: Pantaleone J.
Published: March 2019

When a falling ball chain strikes a surface, a tension is created that pulls the chain downward. This causes a downward acceleration that is larger than free-fall, which has been observed by recent experiments. Here, a theoretical description of this surprising phenomenon is developed. The equation of motion for the falling chain is derived, and then solved for a general form of the tension. The size of the tension needed to produce the observed motion is relatively small and is explained here as coming from the rotation of a link just above where the chain collides with the surface. This simple model is used to calculate the size of the tension in terms of physically measurable quantities: the length and width of a link, the maximum bending angle at a junction, the inclination angle of the surface and the coefficients of friction and restitution between the chain and the surface. The model's predictions agree with the results of current experiments. New experiments are proposed that can test the model.
Retinal and Cortical Determinants of Cortical Magnification in Human Albinism
Authors: Woertz Erica N. , Wilk Melissa A. , Duwell Ethan , Mathis Jedidiah , Carroll Joseph , DeYoe Edgar A.
Published: March 2019

The human fovea lies at the center of the retina and supports high-acuity vision. In normal visual system development, foveal acuity is correlated with both a high density of cone photoreceptors at this location and a magnified retinotopic representation of the fovea in the visual cortex. Both cone density and the cortical area dedicated to each degree of visual space—the latter known as the cortical magnification function—steadily decline with increasing eccentricity from the fovea. In albinism, peak cone density at the fovea and visual acuity are reduced but appear to be normal in the periphery, thus providing a model to explore the correlation between retinal structure, cortical structure, and behavior. Here, we used adaptive optics scanning light ophthalmoscopy to assess retinal cone density and functional magnetic resonance imaging to measure cortical magnification in primary visual cortex of normal controls and individuals with albinism. We find that retinotopic organization is more varied in albinism than previously appreciated, yet cortical magnification outside the fovea is similar to that in controls. Moreover, cortical magnification in albinism and controls exceeds that which might be predicted based on cone density alone, suggesting that reduced foveal cone density in the albinotic retina may be partially counteracted by central connectivity. Together, these results emphasize that central as well as retinal factors must be included to provide a complete picture of aberrant structure and function in genetic conditions such as albinism.
Towards an individualised neural assessment of receptive language in children
Authors: Petit Selene , Badcock Nicholas A. , Grootswagers Tijl , Rich Anina N. , Brock Jon , Nickels Lyndsey , Moerel Denise , Dermody Nadene , Yau Shu , Schmidt Elaine , Woolgar Alexandra
Published: March 2019

Purpose

We aimed to develop a non-invasive neural test of language comprehension to use with non-speaking children for whom standard behavioural testing is unreliable (e.g., minimally-verbal autism). Our aims were three-fold. First, we sought to establish the sensitivity of two auditory paradigms to elicit neural responses in individual neurotypical children. Second, we aimed to validate the use of a portable and accessible electroencephalography (EEG) system, by comparing its recordings to those of a research-grade system. Third, in light of substantial inter-individual variability in individuals’ neural responses, we assessed whether multivariate decoding methods could improve sensitivity.

Methods

We tested the sensitivity of two child-friendly covert N400 paradigms. Thirty-one typically developing children listened to identical spoken words that were either strongly predicted by the preceding context or violated lexical-semantic expectations. Context was given by a cue word (Experiment 1) or sentence frame (Experiment 2) and participants either made an overall judgement on word relatedness or counted lexical-semantic violations. We measured EEG concurrently from a research-grade system, Neuroscan’s SynAmps2, and an adapted gaming system, Emotiv’s EPOC+.

Results

We found substantial inter-individual variability in the timing and topology of N400-like effects. For both paradigms and EEG systems, traditional N400 effects at the expected sensors and time points were statistically significant in around 50% of individuals. Using multivariate analyses, detection rate increased to 88% of individuals for the research-grade system in the sentences paradigm, illustrating the robustness of this method in the face of inter-individual variations in topography.

Conclusions

There was large inter-individual variability in neural responses, suggesting inter-individual variation in either the cognitive response to lexical-semantic violations, and/or the neural substrate of that response. Around half of our neurotypical participants showed the expected N400 effect at the expected location and time point. A low-cost, accessible EEG system provided comparable data for univariate analysis but was not well suited to multivariate decoding. However, multivariate analyses with a research-grade EEG system increased our detection rate to 88% of individuals. This approach provides a strong foundation to establish a neural index of language comprehension in children with limited communication.
Testing the role of cognitive inhibition in physical endurance using high-definition transcranial direct current stimulation over the prefrontal cortex
Authors: Denis Gauthier , Zory Raphael , Radel Rémi
Published: March 2019

The aim of this study was to clarify the role of the prefrontal cortex (PFC) in physical effort regulation. We hypothesized that the PFC would be progressively involved in physical endurance through the engagement of cognitive inhibition, which would be necessary to maintain effort by inhibiting fatigue-related cues. This hypothesis was examined using a double-blind, sham-controlled, within-subjects study (N= 20) using high-definition (HD) transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC). Participants had to maintain a knee extensor contraction at 30% of their maximal force while simultaneously performing an Eriksen flanker task to evaluate their inhibition performance during the task. Anodal stimulation of the dlPFC influenced response to the cognitive task during exercise, as seen by slower response times and better accuracy. However, it did not lead to any measureable improvement in cognitive inhibition and did not influence endurance time. There was no correlation between cognitive inhibition and the maintenance of physical effort. This result could be explained by some methodological limitations of our protocol, and we also provide alternative explanations for the contribution of the PFC in physical endurance.
EPIP: MHC-I epitope prediction integrating mass spectrometry derived motifs and tissue-specific expression profiles
Authors: Hu Weipeng , Qiu Si , Li Youping , Lin Xinxin , Zhang Le , Xiang Haitao , Han Xing , Zhu Sitao , Chen Lei , Li Sha , Li Wenhui , Ren Zhe , Hou GuiXue , Lin Zhilong , Lu Jianliang , Liu Geng , Li Bo , Lee Leo J
Published: March 2019

Background

Accurate prediction of epitopes presented by human leukocyte antigen (HLA) is crucial for personalized cancer immunotherapies targeting T cell epitopes. Mass spectrometry (MS) profiling of eluted HLA ligands, which provides high-throughput measurements of HLA associated peptides in vivo, can be used to faithfully model the presentation of epitopes on the cell surface. In addition, gene expression profiles measured by RNA-seq data in a specific cell/tissue type can significantly improve the performance of epitope presentation prediction. However, although large amount of high-quality MS data of HLA-bound peptides is being generated in recent years, few provide matching RNA-seq data, which makes incorporating gene expression into epitope prediction difficult.

Methods

We collected publicly available HLA peptidome and matching RNA-seq data of 34 cell lines derived from various sources. We built position score specific matrixes (PSSMs) for 21 HLA-I alleles based on these MS data, then used logistic regression (LR) to model the relationship among PSSM score, gene expression and peptide length to predict whether a peptide could be presented in each of the cell line. We further built a universal LR model, termed Epitope Presentation Integrated Prediction (EPIP), based on more than 180,000 unique HLA ligands collected from public sources and ~3,000 HLA ligands generated by ourselves, to predict epitope presentation for 66 common HLA-I alleles.

Results

When evaluating EPIP on large, independent HLA eluted ligand datasets, it performed substantially better than other popular methods, including MixMHCpred (v2.0), NetMHCpan (v4.0), and MHCflurry (v1.2.2), with an average 0.1% positive predictive value (PPV) of 52.01%, compared to 37.24%, 36.96%, 24.90% and 23.76% achieved by MixMHCpred, NetMHCpan-4.0 (EL), NetMHCpan-4.0 (BA) and MHCflurry, respectively. It is also comparable to EDGE, a recent deep learning-based model that is not publicly available, on predicting epitope presentation and selecting immunogenic cancer neoantigens. However, the simplicity and flexibility of EPIP makes it easier to be applied in diverse situations, and we demonstrated this by generating MS data for the HCC4006 cell line and adding the support of HLA-A*33:03 to EPIP. EPIP is publicly available as a web tool < http://epip.genomics.cn/>.

Conclusions

we have developed an easy to use, publicly available epitope prediction tool, EPIP, that incorporates information from both MS and RNA-seq data, and demonstrated its superior performance over existing public methods.
GPseudoClust: deconvolution of shared pseudo-profiles at single-cell resolution
Authors: Strauss Magdalena E , Kirk Paul DW , Reid John E , Wernisch Lorenz
Published: March 2019

Motivation

Many methods have been developed to cluster genes on the basis of their changes in mRNA expression over time, using bulk RNA-seq or microarray data. However, single-cell data may present a particular challenge for these algorithms, since the temporal ordering of cells is not directly observed. One way to address this is to first use pseudotime methods to order the cells, and then apply clustering techniques for time course data. However, pseudotime estimates are subject to high levels of uncertainty, and failing to account for this uncertainty is liable to lead to erroneous and/or over-confident gene clusters.

Results

The proposed method, GPseudoClust, is a novel approach that jointly infers pseudotem-poral ordering and gene clusters, and quantifies the uncertainty in both. GPseudoClust combines a recent method for pseudotime inference with nonparametric Bayesian clustering methods, efficient MCMC sampling, and novel subsampling strategies which aid computation. We consider a broad array of simulated and experimental datasets to demonstrate the effectiveness of GPseudoClust in a range of settings.

Availability

An implementation is available on GitHub: https://github.com/magStra/nonparametricSummaryPSM and https://github.com/magStra/GPseudoClust.

Contact

ms58@sanger.ac.uk

Supplementary information

Supplementary materials are available.
Shared resources between visual attention and visual working memory are allocated through rhythmic sampling
Authors: Balestrieri Elio , Ronconi Luca , Melcher David
Published: March 2019

Attention and Visual Working Memory (VWM) are among the most theoretically detailed and empirically tested constructs in human cognition. Nevertheless, the nature of the interrelation between selective attention and VWM still presents a fundamental controversy: do they rely on the same cognitive resources or not? The present study aims at disentangling this issue by capitalizing on recent evidence showing that attention is a rhythmic phenomenon, oscillating over short time windows. Using a dual-task approach, we combined a classic VWM task with a detection task in which we densely sampled detection performance during the time between the memory and the test array. Our results show that an increment in VWM load was related to a worse detection of near threshold visual stimuli and, importantly, to the presence of an oscillatory pattern in detection performance at ∼5 Hz. Furthermore, our findings suggest that the frequency of this sampling rhythm changes according to the strategic allocation of attentional resources to either the VWM or the detection task. This pattern of results is consistent with a central sampling attentional rhythm which allocates shared attentional resources both to the flow of external visual stimulation and also to the internal maintenance of visual information.
A Role for Gαz in regulating seizure susceptibility
Authors: Hultman Rainbo , Boms Okechi , Mague Stephen , Hughes Dalton , Nadler Victor , Dzirasa Kafui , Casey Patrick J.
Published: March 2019

Much about the molecular mechanisms underlying seizure susceptibility remains unknown. A number of studies have indicated that the neurotrophic factor BDNF plays an important role in mediating seizure susceptibility. Recently, we found that the heterotrimeric G – protein, Gz, which is known to endogenously couple to monoaminergic receptors, such as serotonin, norepinephrine and dopamine receptors, regulates BDNF-induced signaling and development in cortical neurons. Interestingly, several of the receptors that Gz endogenously couples to have also been shown to be associated with seizure phenotypes (5HT1A-serotonin and D2 dopamine). Here we characterized seizure susceptibility in Gz-null mice, behaviorally and electrographically, finding that Gz-null mice have increased seizure susceptibility using a modified version of the pilocarpine model of status epilepticus. Local field potential (LFP) data recorded from six brain regions-amygdala, dorsal hippocampus, ventral hippocampus, motor cortex, somatosensory cortex, and thalamus-showed robust electrographic seizure activity for Gz-null mice compared with low or no seizure activity in wild-type controls.
Risk of differential cancer types over age in families with Li-Fraumeni syndrome: a validation study using multi-center cohorts
Authors: Shin Seung Jun , Dodd Elissa , Peng Gang , Bojadzieva Jasmina , Chen Jingxiao , Amos Chris , Mai Phuong L. , Savage Sharon A. , Ballinger Mandy L. , Thomas David M. , Yuan Ying , Strong Louise C. , Wang Wenyi
Published: March 2019

Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome associated with an autosomal dominant mutation inheritance in the TP53 tumor suppressor gene and a wide spectrum of cancer diagnoses. An accurate estimation of the penetrance of different cancer types in LFS is crucial to improve the clinical characterization and management of high-risk individuals of LFS. Our competing risk-based statistical model incorporates the pedigree structure efficiently into the penetrance estimation and corrects for the ascertainment bias. A set of TP53 penetrance for three cancer types (breast, BR/sarcoma, SA/others, OT) involved in LFS is then estimated from 186 pediatric-sarcoma families collected at MD Anderson Cancer Center. The penetrance was then validated on a mixed cohort of clinically ascertained families with cancer (total number of families=668). The age-dependent onset probability distributions of specific cancer types are different. For breast cancer, the TP53 penetrance goes up at an earlier age than the reported BRCA1/2 penetrance. We validated the prediction performance of the penetrance estimates via two independent cohorts combined (BR=85, SA=540, OT=158). We obtained areas under the ROC curves (AUCs) of 0.92 (BR), 0.75 (SA), and 0.81 (OT). Our R package, LFSPRO, provides risk estimates for the diagnosis of breast cancer, sarcoma, other cancers or death before cancer diagnosis in future.

Significance

Cancer-specific penetrance can facilitate clinical characterization of LFS and will contribute to the management of families at high risk of LFS.
An engineered monomer binding-protein forα-synuclein efficiently inhibits the proliferation of amyloid fibrils
Authors: Agerschou Emil D. , Saridaki Theodora , Flagmeier Patrick , Galvagnion Céline , Komnig Daniel , Nagpal Akansha , Gasterich Natalie , Heid Laetitia , Prasad Vibha , Shaykhalishahi Hamed , Voigt Aaron , Willbold Dieter , Dobson Christopher M. , Falkenburger Björn H. , Hoyer Wolfgang , Buell Alexander K.
Published: March 2019

Removing or preventing the formation ofα-synuclein aggregates is a plausible strategy against Parkinson’s disease. To this end we have engineered theβ-wrapin AS69 to bind monomericα-synuclein with high affinity. In cultured cells, AS69 reduced the occurrence ofα-synuclein oligomers and of visibleα-synuclein aggregates. In flies, AS69 reducedα-synuclein aggregates and the locomotor deficit resulting fromα-synuclein expression in neuronal cells. In a mouse model based on the intracerebral injection of pre-formedα-synuclein seed fibrills (PFFs), AS69 co-injection reduced the density of dystrophic neurites observed three months later. In biophysical experiments invitro, AS69 highly sub-stoichiometrically inhibited auto-catalytic secondary nucleation processes, even in the presence of a large excess of monomer. We present evidence that the AS69-α-synuclein complex, rather than the free AS69, is the inhibitory species responsible for sub-stoichiometric inhibition. These results represent a new paradigm that high affinity monomer binders can be strongly sub-stoichiometric inhibitors of nucleation processes.