bluuebunny/crossref_metadata_2025 huggingface dataset:
Isoperimetric inequalities for quermassintegrals
Authors: Trudinger Neil S.
Published: February 2017

The isoperimetric inequalities of Aleksandrov and Fenchel for
quermassintegrals
(cross sectional measures) of convex domains in Euclidean space are established for non-convex domains, subject to natural curvature conditions. The techniques are new and draw upon the theory of Monge–Ampère type equations related to previous work of the author on equations of prescribed curvature.

Les inégalités isopérimétriques d’Aleksandrov et Frenchel pour les
quermassintegrals
dans le cas de domaines convexes d’espaces euclidiens sont établies pour un domaine non convexe vérifiant des conditions naturelles de courbure. Les techniques sont neuves et reposent sur des équations de type Monge–Ampère reliées à un travail antérieur de l’auteur sur des équations à courbure prescrite.
Étude qualitative des solutions réelles d’une équation différentielle liée à l’équation de Ginzburg-Landau
Authors: Hervé Rose-Marie , Hervé Michel
Published: February 2017

We consider the ordinary differential equation satisfied by the real functions

f (r)

such that the

u(re^{iθ}) = f (r)e^{iqθ}

(

q\in Ν^*

) are solutions of the Ginzburg–Landau equation

−\mathrm{\Delta }u = u(1−|u|^{2})

. We show: that such a function

f (r)

, if defined on a neighbourhood of

0

, is analytic and uniquely determined by the number

a= f(q) (0)/q!

; that one value of a only, say

A

, yields a strictly increasing function

f (r)

running from

0

to

1

as

r

runs from

0

to

+∞

, of which we give an asymptotic expansion for

r → +∞

. We also prove that any

a \in ] – A, A [\setminus \{0\}

yields an indefinitely oscillating function

f (r)

, and that the length of the interval between two consecutive zeroes has

π

as its limit.

Nous étudions l’équation différentielle satisfaite par les fonctions réelles

f (r)

telles que

u (re^{iθ}) = f (r) e^{iqθ}

(

q\in N^*

) soit solution de l’équation de Ginzburg–Landau

−\mathrm{\Delta }u = u(1−|u|^{2})

. Nous montrons: qu’une telle fonction

f (r)

, si elle est définie sur un voisinage de

0

, est analytique et parfaitement déterminée par le nombre

a = f(q) (0)/q!

; qu’une seule valeur de

a

, soit

A

, donne une fonction

f (r)

croissant strictement de

0

à

1

quand

r

croît de

0

à

+∞

, et dont nous donnons un développement asymptotique pour

r → +∞

. Nous montrons aussi que toute valeur

a\in ] – A, A [\setminus \{0\}

donne une fonction

f (r)

oscillant indéfiniment, et que l’écart entre deux zéros consécutifs a pour limite

π

.
New Inequalities for the Jacobian
Authors: Iwaniec T. , Greco L.
Published: February 2017

We derive integral estimates for the Jacobian by using the Rochberg–Weiss theory of nonlinear commutators. A refinement of Müller’s result is obtained. We demonstrate how local estimates can be used to improve the degree of integrability of the Jacobian.

On établit des estimations intégrales pour le jacobien au moyen de la théorie des commutateurs non linéaires par Rochberg–Weiss. On obtient ainsi un raffinement du résultat de Müller. On démontre comment l’emploi des estimations locales permit d’améliorer le degré d’intégrabilité du jacobien.
Multiple solutions of a semilinear elliptic equation in ℝN
Authors: Cao Dao-Min
Published: February 2017

In this paper, we are concerned with the existence of multiple solutions of

−\mathrm{\Delta }u + u = \mathrm{\lambda }b(x)\left|u\right|^{p−1}u + c(x)\left|u\right|^{q−1}u

where

1 < p

,

q < \frac{\mathrm{N} + 2}{\mathrm{N}−2}

if

N ≧ 3

,

1 < p

,

q < + ∞

if

N = 2

,

λ > 0

.

We obtain the existence of multiple solutions by using concentrations-compactness method and dual variational principle to establish the corresponding existence of critical points.

Nous obtenons dans cet article un résultat d’existence et de multiplicité de solutions de

−\mathrm{\Delta }u + u = \mathrm{\lambda }b(x)\left|u\right|^{p−1}u + c(x)\left|u\right|^{q−1}u

où

1 < p

,

q < \frac{\mathrm{N} + 2}{\mathrm{N}−2}

,

N ≧ 3

,

1 < p

,

q < + ∞

si

N = 2

,

λ > 0

.

Ces résultats sont prouvés à l’aide de la méthode de concentration-compacité et de principes variationnels duaux pour obtenir l’existence des points critiques correspondants.
The minimal period problem of classical Hamiltonian systems with even potentials
Authors: Long Yiming
Published: February 2017

In this paper, we study the existence of periodic solutions with prescribed minimal period for even superquadratic autonomous second order Hamiltonian systems defined on

\mathbf R^n

with no convexity assumptions. We use a direct variational approach for this problem on a

W^{1, 2}

space of functions invariant under the action of a transformation group isomorphic to the Klein Fourgroup

\mathbf V_4 = \mathbf Z_2 \oplus \mathbf Z_2

to find symmetric periodic solutions, and prove a new iteration inequality on the Morse index by iterating such functions properly. Using these tools and the Mountain-pass theorem, we show that for every

T > 0

, the above mentioned system possesses a

T

-periodic solution

x(t)

with minimal period

T

or

T/3

, and this solution is even about

t = 0, T/2

and odd about

t = T/4, 3 T/4

.

Dans cet article, on étudie l’existence de solutions périodiques avec la période minimale prescrit pour les systèmes hamiltoniens pairs autonomes d’ordre secondaire à croissance super-quadratique, définis dans

\mathbf R^n

sans hypothèse de convexité. Pour trouver des solutions périodiques symétriques, on utilise une approche directe variationnelle pour ce problème dans

W^{1, 2}

, espace de fonctions invariantes sous l’action d’un groupe de transformation, qui est isomorphe avec le Quatre-groupe de Klein

\mathbf V_4 = \mathbf Z_2 \oplus \mathbf Z_2

, et prouve les nouvelles inégalités d’itération sur les indices de Morse pour l’itération propre de telles fonctions. En utilisant ces outils et le théorème de Col de Montagne, on montre que pour chaque

T > 0

le système ci-dessus possède une solution

T

-période

x(t)

avec la periode minimale

T

ou

T/3

, et que cette solution est paire sur

t = 0, T/2

et impaire sur

t = T/4, 3 T/4

.
Pulses of Rising Magma in Sierra Nevada's Past
Authors: Cook Terri
Published: February 2017

A detailed study of layered igneous material at California's Fisher Lake offers a novel approach to identifying the pathways and timescales of individual magma pulses in volcanic arcs.
The role of PKCζ in cord blood T-cell maturation towards Th1 cytokine profile and its epigenetic regulation by fish oil
Authors: Harb Hani , Irvine James , Amarasekera Manori , Hii Charles S. , Kesper Dörthe A. , Ma YueFang , D’Vaz Nina , Renz Harald , Potaczek Daniel P. , Prescott Susan L. , Ferrante Antonio
Published: February 2017

While immunodeficiency of immaturity of the neonate has been considered important as the basis for unusual susceptibility to infection, it has also been recognized that the ability to progress from an immature Th2 cytokine predominance to a Th1 profile has relevance in determining whether children will develop allergy, providing an opportunity for epigenetic regulation through environmental pressures. However, this notion remains relatively unexplored. Here, we present evidence that there are two major control points to explain the immunodeficiency in cord blood (CB) T-cells, a deficiency in interleukin (IL)-12 (IL-12) producing and IL-10 overproducing accessory cells, leading to a decreased interferon γ (IFNγ) synthesis and the other, an intrinsic defect in T-cell protein kinase C (PKC) ζ (PKCζ) expression. An important finding was that human CB T-cells rendered deficient in PKCζ, by shRNA knockdown, develop into low tumour necrosis factor α (TNFα) and IFNγ but increased IL-13 producing cells. Interestingly, we found that the increase in PKCζ levels in CB T-cells caused by prenatal supplementation with fish oil correlated with modifications of histone acetylation at the PKCζ gene (PRKCZ) promoter. The data demonstrate that PKCζ expression regulates the maturation of neonatal T-cells into specific functional phenotypes and that environmental influences may work via PKCζ to regulate these phenotypes and disease susceptibility.
Principles for circadian orchestration of metabolic pathways
Authors: Thurley Kevin , Herbst Christopher , Wesener Felix , Koller Barbara , Wallach Thomas , Maier Bert , Kramer Achim , Westermark Pål O
Published: February 2017

Significance

Circadian (24-h) rhythms influence the behavior and physiology of many organisms. These rhythms are generated at the gene expression level, causing the waxing and waning of protein abundances. Metabolic enzymes are affected, but the principles for the propagation of enzyme rhythmicity to cellular metabolism as quantified by fluxes through metabolic pathways and metabolite concentrations are not understood. We used the mathematics of chemical kinetics to systematically investigate how rhythms in enzyme activity are propagated to pathway fluxes and concentrations. It turned out that rhythms are often optimally propagated when several enzyme activities are rhythmic but with different timing. We performed measurements of circadian enzyme activities in mouse muscle that confirmed such timing differences.
Evaluation of corrosion and wear resistance of friction stir welded ZK60 alloy
Authors: Liu Dejia , Xin Renlong , Zhao Longzhi , Hu Yong , Zhang Jian
Published: February 2017

Owing to the low corrosion and wear resistance of magnesium alloy, surface properties are the key factors affecting its application. But few studies have concentrated on the surface properties of friction stir welded Mg–Zn–Zr alloy. The aim of the present paper is to investigate the effects of friction stir welding (FSW) and subsequent ageing on the surface corrosion and wear resistance of ZK60 alloy. It is found that due to the significant grain refinement and redistribution of precipitates, the surface corrosion and wear resistance of ZK60 plates are enhanced by FSW. Morphology of inter-granular corrosion in base metal is changed into pitting corrosion after welding. Subsequent ageing can significantly reduce the corrosion resistance of the welded plates.
Differences in Functional Outcome Across Subtypes with Spetzler-Martin Grade II Arteriovenous Malformations
Authors: Hung Alice L. , Yang Wuyang , Westbroek Erick M. , Garzon-Muvdi Tomas , Caplan Justin M. , Braileanu Maria , Wang Joanna Y. , Colby Geoffrey P. , Coon Alexander L. , Tamargo Rafael J. , Huang Judy
Published: February 2017

BACKGROUND: The Spetzler-Martin grading system for brain arteriovenous malformations (AVMs) is based on size (S), eloquence (E), and deep venous drainage (V). However, variation exists due to subgroup heterogeneity. While previous studies have demonstrated variations in outcomes within grade III AVMs, no studies have focused on grade II AVM subtypes.

OBJECTIVE: We aim to delineate how functional outcomes differ among patients with subtypes of grade II AVMs.

METHODS: We retrospectively reviewed patients with AVMs evaluated at our institution from 1990 to 2013. Grade II AVMs were divided into 3 subtypes: group 1 (S2V0E0), group 2 (S1V0E1), and group 3 (S1V1E0). Baseline characteristics were compared, and functional status was assessed using the modified Rankin Scale (mRS) at pretreatment and last follow-up. Differences in mRS between the 2 time points were compared.

RESULTS: A total of 208 grade II patients (34.0%) were retrieved from 611 graded patients. After accounting for missing data, our cohort consisted of 137 patients. Mean age of all patients was 37.2 years, with 74 females (54.0%). No significant difference was observed across subgroups for pretreatment mRS (P = .096), treatment modalities (P = .943), follow-up durations (P = .125), and mRS at last follow-up (P = .716). In a subgroup analysis between group 1 and group 3, more patients with worsened mRS were observed in group 3 (P = .039). This distinction was further confirmed in surgically treated patients (P = .049), but not in patients treated with radiosurgery (P = .863).

CONCLUSION: Subtypes of grade II AVMs portend different posttreatment gains in functional outcome. Group 1 (S2V0E0) patients had the best functional outcome gain from treatment, while group 3 (S1V1E0) patients fared less well, particularly with surgical treatment.
A risk assessment framework for seed degeneration: Informing an integrated seed health strategy for vegetatively-propagated crops
Authors: Thomas-Sharma S. , Andrade-Piedra J. , Carvajal Yepes M. , Hernandez Nopsa J. F. , Jeger M. J. , Jones R. A. C. , Kromann P. , Legg J. P. , Yuen J. , Forbes G. A. , Garrett K. A.
Published: February 2017

Pathogen build-up in vegetative planting material, termed seed degeneration, is a major problem in many low-income countries. When smallholder farmers use seed produced on-farm or acquired outside certified programs, it is often infected. We introduce a risk assessment framework for seed degeneration, evaluating the relative performance of individual and combined components of an integrated seed health strategy. The frequency distribution of management performance outcomes was evaluated for models incorporating biological and environmental heterogeneity, with the following results. (1) On-farm seed selection can perform as well as certified seed, if the rate of success in selecting healthy plants for seed production is high; (2) When choosing among within-season management strategies, external inoculum can determine the relative usefulness of ‘incidence-altering management’ (affecting the proportion of diseased plants/seeds) and rate-altering management (affecting the rate of disease transmission in the field); (3) Under severe disease scenarios, where it is difficult to implement management components at high levels of effectiveness, combining management components can produce synergistic benefits and keep seed degeneration below a threshold; (4) Combining management components can also close the yield gap between average and worst-case scenarios. We also illustrate the potential for expert elicitation to provide parameter estimates when data are unavailable.
Focus: The interface between data collection and data processing in cryo-EM
Authors: Biyani Nikhil , Righetto Ricardo D. , McLeod Robert , Caujolle-Bert Daniel , Castano-Diez Daniel , Goldie Kenneth N. , Stahlberg Henning
Published: February 2017

We present a new software package called Focus that interfaces cryo-transmission electron microscopy (cryo-EM) data collection with computer image processing. Focus creates a user-friendly environment to import and manage data recorded by direct electron detectors and perform elemental image processing tasks in a high-throughput manner while new data is being acquired at the microscope. It provides the functionality required to remotely monitor the progress of data collection and data processing, which is essential now that automation in cryo-EM allows a steady flow of images of single particles, two-dimensional crystals, or electron tomography data to be recorded in overnight sessions. The rapid detection of any errors that may occur greatly increases the productivity of recording sessions at the electron microscope.
Spindle assembly checkpoint satisfaction occurs through end-on but not lateral kinetochore-microtubule interactions under tension
Authors: Kuhn Jonathan , Dumont Sophie
Published: February 2017

To ensure accurate chromosome segregation, the spindle assembly checkpoint (SAC) prevents anaphase until all kinetochores attach to the spindle. What signals the SAC monitors remains unclear. We do not know the contributions of different microtubule attachment features, or tension from biorientation, to SAC satisfaction in normal mitosis - or how these possible cues change during attachment. Here, we quantify concurrent Mad1 intensity, reporting on SAC silencing, and real-time attachment geometry, occupancy, and tension at individual mammalian kinetochores. We show that Mad1 loss from the kinetochore occurs in switch-like events with robust kinetics, and that metaphase-like tension across sister kinetochores is established just before Mad1 loss events at the first sister. We demonstrate that CenpE-mediated lateral attachment of the second sister can persistently generate this metaphase-like tension prior to biorientation, likely stabilizing sister end-on attachment, yet cannot induce Mad1 loss from that kinetochore. Instead, Mad1 loss begins after several end-on microtubules attach. Thus, end-on attachment provides geometry-specific molecular cues, or force on specific kinetochore linkages, that other attachment geometries cannot provide.

The spindle assembly checkpoint (SAC) delays anaphase until kinetochores are properly attached to the spindle. The authors demonstrate that the SAC monitors geometry-specific molecular cues, or force on specific kinetochore linkages, that “end-on” but not “lateral” attachments generating persistent tension can provide.
Hybridization affects life-history traits and host specificity inDiorhabdaspp
Authors: Bitume E.V. , Bean D. , Stahlke A.R. , Hufbauer R.A.
Published: February 2017

Hybridization is an influential evolutionary process that has been viewed alternatively as an evolutionary dead-end or as an important creative evolutionary force. In colonizing species, such as introduced biological control agents, hybridization can negate the effects of bottlenecks and genetic drift through increasing genetic variation. Such changes could be beneficial to a biological control program by increasing the chances of establishment success. However, hybridization can also lead to the emergence of transgressive phenotypes that could alter host specificity; an important consideration when assessing potential non-target impacts of planned agents. In a series of lab experiments, we investigated the effects of hybridization between three species ofDiorhabdareleased to control invasiveTamarix(saltcedar) on life history traits through two generations, and through the third generation for one cross. Depending on the cross, hybridization had either a positive or neutral impact on development time, adult mass, and fecundity. We evaluated preference for the target (saltcedar) relative to a non-target hostTamarixaphylla(athel), and found host specificity patterns varied in two of the three hybrids, demonstrating the possibility for hybridization to alter host preference. Importantly, the overall effects of hybridization were inconsistent by cross, leading to unpredictability in the outcome of using hybrids in biological control.
Imputation aware tag SNP selection to improve power for multi-ethnic association studies
Authors: Wojcik Genevieve L. , Fuchsberger Christian , Taliun Daniel , Welch Ryan , Martin Alicia R , Shringarpure Suyash , Carlson Christopher S. , Abecasis Goncalo , Kang Hyun Min , Boehnke Michael , Bustamante Carlos D. , Gignoux Christopher R. , Kenny Eimear E.
Published: February 2017

The emergence of very large cohorts in genomic research has facilitated a focus on genotype-imputation strategies to power rare variant association. Consequently, a new generation of genotyping arrays are being developed designed with tag single nucleotide polymorphisms (SNPs) to improve rare variant imputation. Selection of these tag SNPs poses several challenges as rare variants tend to be continentally-or even population-specific and reflect fine-scale linkage disequilibrium (LD) structure impacted by recent demographic events. To explore the landscape of tag-able variation and guide design considerations for large-cohort and biobank arrays, we developed a novel pipeline to select tag SNPs using the 26 population reference panel from Phase of the 1000 Genomes Project. We evaluate our approach using leave-one-out internal validation via standard imputation methods that allows the direct comparison of tag SNP performance by estimating the correlation of the imputed and real genotypes for each iteration of potential array sites. We show how this approach allows for an assessment of array design and performance that can take advantage of the development of deeper and more diverse sequenced reference panels. We quantify the impact of demography on tag SNP performance across populations and provide population-specific guidelines for tag SNP selection. We also examine array design strategies that target single populations versus multi-ethnic cohorts, and demonstrate a boost in performance for the latter can be obtained by prioritizing tag SNPs that contribute information across multiple populations simultaneously. Finally, we demonstrate the utility of improved array design to provide meaningful improvements in power, particularly in trans-ethnic studies. The unified framework presented will enable investigators to make informed decisions for the design of new arrays, and help empower the next phase of rare variant association for global health.
QuASAR-MPRA: Accurate allele-specific analysis for massively parallel reporter assays
Authors: Kalita Cynthia A. , Moyerbrailean Gregory A. , Brown Christopher , Wen Xiaoquan , Luca Francesca , Pique-Regi Roger
Published: February 2017

Motivation

The majority of the human genome is composed of non-coding regions containing regulatory elements such as enhancers, which are crucial for controlling gene expression. Many variants associated with complex traits are in these regions, and may disrupt gene regulatory sequences. Consequently, it is important to not only identify true enhancers but also to test if a variant within an enhancer affects gene regulation. Recently, allele-specific analysis in high-throughput reporter assays, such as massively parallel reporter assays (MPRA), have been used to functionally validate non-coding variants. However, we are still missing high-quality and robust data analysis tools for these datasets.

Results

We have further developed our method for allele-specific analysis QuASAR (quantitative allele-specific analysis of reads) to analyze allele-specific signals in barcoded read counts data from MPRA. Using this approach, we can take into account the uncertainty on the original plasmid proportions, over-dispersion, and sequencing errors. The provided allelic skew estimate and its standard error also simplifies meta-analysis of replicate experiments. Additionally, we show that a beta-binomial distribution better models the variability present in the allelic imbalance of these synthetic reporters and results in a test that is statistically well calibrated under the null. Applying this approach to the MPRA data by Tewheyet al.(2016), we found 602 SNPs with significant (FDR 10%) allele-specific regulatory function in LCLs. We also show that we can combine MPRA with QuASAR estimates to validate existing experimental and computational annotations of regulatory variants. Our study shows that with appropriate data analysis tools, we can improve the power to detect allelic effects in high throughput reporter assays.

Availability

http://github.com/piquelab/QuASAR/tree/master/mpra

Contact

fluca@wayne.edu;rpique@wayne.edu
Filter-banks and artificial intelligence in seizure detection using electroencephalograms
Authors: Pinto-Orellana M. A. , Cerqueira F. R.
Published: February 2017

Epilepsy is the most typical neurological disease in the world, and it implies an expensive and specialized diagnosis process based on electroencephalograms and video recordings. We developed a method that only requires the brainwave provided by the difference between two standard-located electrodes. Our proposed technique separates the original signal using a filter array with three different types of filters, and then extracts several features based on information theory and statistical information. In our study, we found that only 10 characteristics, of which the most important are related to higher frequencies, are required to offer an accuracy of 94%, a specificity of 95% and a sensitivity of 87% using C4.5 decision trees.
Reliable CRISPR/Cas9 genome engineering inCaenorhabiditis elegansusing a single efficient sgRNA and an easily selectable phenotype
Authors: El Mouridi Sonia , Lecroisey Claire , Tardy Philippe , Mercier Marine , Leclercq-Blondel Alice , Zariohi Nora , Boulin Thomas
Published: February 2017

CRISPR/Cas9 genome engineering strategies allow the directed modification of theC. elegansgenome to introduce point mutations, generate knock-out mutants and insert coding sequences for epitope or fluorescent tags. Three practical aspects however complicate such experiments. First, the efficiency and specificity of single-guide RNAs (sgRNA) cannot be reliably predicted. Second, the detection of animals carrying genome edits can be challenging in the absence of clearly visible or selectable phenotypes. Third, the sgRNA target site must be inactivated after editing to avoid further double-strand break events. We describe here a strategy that addresses these complications by transplanting the protospacer of a highly efficient sgRNA into a gene of interest to render it amenable to genome engineering. This sgRNA targeting thedpy-10gene generates genome edits at comparatively high frequency. We demonstrate that the transplanted protospacer is cleaved at the same time as thedpy-10gene. Our strategy generates scarless genome edits because it no longer requires the introduction of mutations in endogenous sgRNA target sites. Modified progeny can be easily identified in the F1 generation, which drastically reduces the number of animals to be tested by PCR or phenotypic analysis. Using this strategy, we reliably generated precise deletion mutants, transcriptional reporters, and translational fusions with epitope tags and fluorescent reporter genes. In particular, we report here the first use of the new red fluorescent protein mScarlet in a multicellular organism. wrmScarlet, aC. elegans-optimized version, dramatically surpassed TagRFP-T by showing an 8-fold increase in fluorescence in a direct comparison.
Asian lineage of Zika virus RNA pseudoknot may induce ribosomal frameshift and produce a new neuroinvasive protein ZIKV-NS1’
Authors: Tambonis Tiago , Contessoto Vinícius G. , Bittar Cíntia , Calmon Marília F. , Nogueira Maurício L. , Rahal Paula , Leite Vitor B. P.
Published: February 2017

Zika virus (ZIKV) is a threat to humanity, and understanding its neuroinvasiveness is a major challenge. Microcephaly observed in neonates in Brazil is associated with ZIKV that belongs to the Asian lineage. What distinguishes the neuroinvasiveness between the RNA lineages from Asia and Africa is still unknown. Here we identify an aspect that may explain the different behavior between the two lineages. The distinction between the two groups is the occurrence of an alternative protein NS1’ (ZIKV-NS1’), which happens through a pseudoknot in the virus RNA that induces a ribosomal frameshift. Presence of NS1’ protein is also observed in otherFlavivirusthat are neuroinvasive, and when NS1’ production issuppressed, neuroinvasiveness is reduced.1This evidence gives grounds to suggest that the ZIKV-NS1’ occurring in the Asian lineage is responsible for neuro-tropism, which causes the neuro-pathologies associated with ZIKV infection, of which microcephaly is the most dev astating. The existence of ZIKV-NS1’, which only exists in the Asian lineage, was inferred through bioinformatic methods, and it has yet to be experimentally observed. If its occurrence is confirmed, it will be a potential target in fighting the neuro-diseases associated with ZIKV.
Immune Loss as a Driver of Coexistence During Host-Phage Coevolution
Authors: Weissman Jake L , Holmes Rayshawn , Barrangou Rodolphe , Moineau Sylvain , Fagan William F , Levin Bruce , Johnson Philip L F
Published: February 2017

Bacteria and their viral pathogens face constant pressure for augmented immune and infective capabilities, respectively. Under this reciprocally imposed selective regime, we expect to see a runaway evolutionary arms race, ultimately leading to the extinction of one species. Despite this prediction, in many systems host and pathogen coexist with minimal coevolution even when well-mixed. Previous work explained this puzzling phenomenon by invoking fitness tradeoffs, which can diminish an arms race dynamic. Here we propose that the regular loss of immunity by the bacterial host can also produce host-phage coexistence. We pair a general model of immunity with an experimental and theoretical case study of the CRISPR-Cas immune system to contrast the behavior of tradeoff and loss mechanisms in well-mixed systems. We find that, while both mechanisms can produce stable coexistence, only immune loss does so robustly within realistic parameter ranges.
The Potential Role of Genetic Assimilation during Maize Domestication
Authors: Lorant Anne , Pedersen Sarah , Holst Irene , Hufford Matthew B. , Winter Klaus , Piperno Dolores , Ross-Ibarra Jeffrey
Published: February 2017

Domestication research has largely focused on identification of morphological and genetic differences between extant populations of crops and their wild relatives. Little attention has been paid to the potential effects of environment despite substantial known changes in climate from the time of domestication to modern day. Recent research, in which maize and teosinte (i.e., wild maize) were exposed to environments similar to the time of domestication, resulted in a plastic induction of domesticated phenotypes in teosinte and little response to environment in maize. These results suggest that early agriculturalists may have selected for genetic mechanisms that cemented domestication phenotypes initially induced by a plastic response of teosinte to environment, a process known as genetic assimilation. To better understand this phenomenon and the potential role of environment in maize domestication, we examined differential gene expression in maize (Zea mays ssp. mays) and teosinte (Zea mays ssp. parviglumis) between past and present conditions. We identified a gene set of over 2000 loci showing a change in expression across environmental conditions in teosinte and invariance in maize. In fact, overall we observed both greater plasticity in gene expression and more substantial re-wiring of expression networks in teosinte across environments when compared to maize. While these results suggest genetic assimilation played at least some role in domestication, genes showing expression patterns consistent with assimilation are not significantly enriched for previously identified domestication candidates, indicating assimilation did not have a genome-wide effect.
Beyond a Liberal Critique of ‘Trickle Down': Urban Planning in the City of Malmö
Authors: Holgersen Ståle , Baeten Guy
Published: February 2017

This article scrutinizes the much used, but less examined, concept of ‘trickle down' in an urban setting. We make a distinction between the production of and distribution in the city, and argue that trickle down in contemporary urban policy could be regarded as the liberal link between production and distribution. Based on interviews with key figures and document analyses, we look at the transformation of the Swedish city of Malmö from an industrial to a post‐industrial city, where, during the last two decades, we have found three concurrent components: the ideology of trickle down; several urban policy programs and governmental policies to ‘make' money and resources trickle down; as well as increased economic polarization and segregation. A liberal critique of trickle down would argue that market mechanisms cannot by themselves solve distribution, and that government policies therefore are needed. We argue for the need to go beyond a liberal critique of trickle down and stress how unequal distribution is built into the unequal production of the city.
SWATMOD‐Prep: Graphical User Interface for Preparing Coupled SWAT‐MODFLOW Simulations
Authors: Bailey Ryan , Rathjens Hendrik , Bieger Katrin , Chaubey Indrajeet , Arnold Jeffrey
Published: February 2017

This article presents SWATMOD‐Prep, a graphical user interface that couples a SWAT watershed model with a MODFLOW groundwater flow model. The interface is based on a recently published SWAT‐MODFLOW code that couples the models via mapping schemes. The spatial layout of SWATMOD‐Prep guides the user through the process of importing shape files (sub‐basins, hydrologic response units [HRUs], river network) from an existing SWAT model, creating a grid, performing necessary geo‐processing operations to link the models, writing out SWAT‐MODFLOW files, and running the simulation. The option of creating a new single‐layer MODFLOW model for near‐surface alluvial aquifers is available, with the user prompted to provide groundwater surface elevation (through a digital elevation model), aquifer thickness, and necessary aquifer parameter values. The option of simulating nitrate transport in the aquifer also is available, using the reactive transport model RT3D. The interface is in the public domain. It is programmed in Python, with various software packages used for geo‐processing operations (e.g., selection, intersection of rasters) and inputting/outputting data, and is written for Windows. The use of SWATMOD‐Prep is demonstrated for the Little River Experimental Watershed, Georgia. SWATMOD‐Prep and SWAT‐MODFLOW executables are available with an accompanying user's manual at: http://swat.tamu.edu/software/swat-modflow/. The user's manual also accompanies this article as Supporting Information.
Harm avoidance and childhood adversities in patients with obsessive–compulsive disorder and their unaffected first‐degree relatives
Authors: Bey K. , Lennertz L. , Riesel A. , Klawohn J. , Kaufmann C. , Heinzel S. , Grützmann R. , Kathmann N. , Wagner M.
Published: February 2017

Objective

The etiology of obsessive–compulsive disorder (OCD) is assumed to involve interactions between genetically determined vulnerability factors and significant environmental features. Here, we aim to investigate how the personality trait harm avoidance and the experience of childhood adversities contribute to OCD.

Method

A total of 169 patients with OCD, 157 healthy comparison subjects, and 57 unaffected first‐degree relatives of patients with OCD participated in the study. Harm avoidance was assessed using the Temperament and Character Inventory, and the severity of childhood adversities was measured with the Childhood Trauma Questionnaire.

Results

Both patients with OCD and relatives showed elevated levels of harm avoidance compared to controls. Furthermore, patients exhibited significantly higher scores than relatives. This linear pattern was observed throughout all subscales of harm avoidance, and remained stable after controlling for the severity of depressive and obsessive–compulsive symptoms. With regard to childhood adversities, patients with OCD reported higher levels than relatives and controls.

Conclusion

Our results provide further evidence for a diathesis‐stress model of OCD. While patients and unaffected relatives share elevated levels of harm avoidance, supporting the role of harm avoidance as an endophenotype of OCD, a heightened severity of childhood adversity was only observed in patients. The assumed biological underpinnings of these findings are discussed.
Cytochrome P450‐mediated interaction between perazine and risperidone: implications for antipsychotic polypharmacy
Authors: Paulzen Michael , Haen Ekkehard , Hiemke Christoph , Stegmann Benedikt , Lammertz Sarah E. , Gründer Gerhard , Schoretsanitis Georgios
Published: February 2017

Background

Although clinically widespread, scientific evidence for antipsychotic polypharmacy is still limited. Combining different drugs increases the potential for drug–drug interactions, enhancing the risk of adverse drug reactions. We aimed to unravel the potential pharmacokinetic interactions between risperidone (RIS) and perazine.

Methods

Using a therapeutic drug monitoring database containing plasma concentrations of RIS and its active metabolite [9‐hydroxyrisperidone (9‐OH‐RIS)], we considered two groups: a group of patients under antipsychotic monotherapy with RIS (n = 40) and a group of patients that was comedicated with perazine (n = 16). Groups were matched for demographic characteristics and daily dosage of RIS. Plasma concentrations, concentrations corrected for the dose (C/D) of RIS, 9‐OH‐RIS and the active moiety (RIS + 9‐OH‐RIS), as well as the metabolic ratios of concentrations of 9‐OH‐RIS/RIS, were compared using nonparametric tests.

Results

All parameters other than plasma concentrations and the C/D ratio of 9‐OH‐RIS differed between groups. Median values for plasma concentrations of the active moiety and C/D of the active moiety were higher in the perazine group (P < 0.001 and P < 0.001, respectively). Differences were driven by variations in the plasma concentrations and C/D of RIS, which were higher in the perazine group (P < 0.001 and P < 0.001, respectively). Metabolic ratios were lower in the perazine group (P = 0.003).

Discussion

The coadministration of perazine in RIS‐medicated patients leads to significantly higher plasma concentrations and C/D values of RIS and its active moiety, and a lower metabolic ratio, reflecting the cytochrome P450 (CYP) 2D6 phenotype. We suggest that the mechanism underlying the effect of perazine on RIS metabolism is based on an inhibition of CYP2D6 and CYP3A4 activity.
Putting knowledge into practice: Does information on adverse drug interactions influence people's dosing behaviour?
Authors: Dohle Simone , Dawson Ian G. J.
Published: February 2017

Objective

Adverse drug events relating to drug–drug interactions are a common cause of patient harm. Central to avoiding this harm is the patients’ understanding that certain drug combinations present a synergistic risk. Two studies tested whether providing individuals with information about a drug combination that presents a synergistic (cf. additive) risk would elicit higher perceived risk and, therefore, would result in greater precaution in terms of dosing behaviour.

Design

Both studies employed an experimental design.

Methods

Participants were presented with a scenario describing how two symptoms of an infection could each be treated by a different drug. In Experiment 1, information about the effects of combining the two drugs was varied: (1) no information, (2) combination elicits an additive risk, or (3) combination elicits a synergistic risk. In Experiment 2, the size of the risk (small or large) and the participant's role (patient or doctor) was also varied.

Results

In both experiments, perceived risk and negative affect increased in response to information about the increased probability of side effects from the drug–drug interaction. Despite these increases, participants did not adjust their drug dosing behaviour in either experiment: Dosing was similar when these interactions were large or small, or when they were due to synergistic or additive effects.

Conclusions

People may struggle to transfer their knowledge of drug–drug interaction risks into decision‐making behaviours. Care should be taken not to assume that holding accurate risk perceptions of a drug's side effect will result in decisions that help avoid adverse drug events.

Statement of contribution

What is already known on this subject?

Adverse effects of drug–drug interactions are a cause of hospital admissions and increase morbidity and mortality.

Patients’ understanding that certain drug combinations present a synergistic risk is crucial to avoid harm.

It is not clear whether synergistic drug interactions increase risk perception and influence dosing decisions.

What does this study add?

Perceived risk and negative affect increased in response to synergistic risk information.

Despite these increases, participants did not adjust their drug dosing behaviour.

People struggle to transfer their knowledge of drug‐related risks into behavioural decisions.
Vitamin D regulates immunoglobulin mucin domain molecule‐4 expression in dendritic cells
Authors: Liu Z.‐Q. , Li M.‐G. , Geng X.‐R. , Liu J. , Yang G. , Qiu S.‐Q. , Liu Z.‐G. , Yang P.‐C.
Published: February 2017

Background

Dendritic cell (DC)‐derived immunoglobulin domain molecule (TIM)4 plays a critical role in the initiation of T helper (Th)2 polarization. Vitamin D (VitD) involves the regulation of a number of immune responses.

Objectives

This study tests a hypothesis that VitD regulates TIM4 expression in DCs.

Methods

Peripheral blood samples were collected from patients with allergic rhinitis (AR) and healthy subjects. DCs were isolated from the samples and analyzed for the expression of TIM4.

Results

We observed that the levels of calcitriol, the active form of VitD3, in the sera of AR patients were lower than that in healthy subjects. The peripheral DC expressed higher levels of TIM4 and lower levels of VDR. A negative correlation was identified between the data of serum calcitriol and TIM4 in DCs. Exposure DCs to calcitriol in the culture increased the expression of VDR. We also found that VDR bound to the TIM4 promoter locus in DCs to repress the TIM4 gene transcription and expression.

Conclusions and clinical relevance

VitD deficiency may contribute to the pathogenesis of AR by increasing the TIM4 expression. The results suggest that to regulate the serum calcitriol levels and the expression of VDR in DCs may be necessary to be taken into account in the treatment of AR.
Conjunctival provocation test in diagnosis of peanut allergy in children
Authors: Lindvik H. , Lødrup Carlsen K. C. , Mowinckel P. , Navaratnam J. , Borres M. P. , Carlsen K.‐H.
Published: February 2017

Background

Peanut allergy frequently causes severe allergic reactions. Diagnosis includes detection of IgE to peanuts in serum or by skin prick tests. While children may have allergic sensitization without having clinical peanut allergy, oral peanut challenge is often required for accurate diagnosis. The conjunctival provocation test is used for diagnosis and evaluation of treatment effect in inhalant allergies, but it has not been evaluated as a tool for diagnosing peanut allergy.

Objective

To investigate whether the conjunctival provocation tests may be feasible, accurate and safe in diagnosing clinically relevant peanut allergy in patients with suspected peanut allergy.

Methods

This cross‐sectional case–control study in children with clinical or laboratory suspected peanut allergy included 102 children recruited from the regional paediatric departments and specialist practices during one year from April 2011. A peanut‐tolerant control group of 28 children of similar age was recruited locally. A double‐blind placebo‐controlled conjunctival provocation test with peanut extract was performed in all children, while oral peanut provocation was performed as double‐blind placebo‐controlled challenge in children with suspected peanut allergy and as an open challenge in the control children.

Results

All 81 children with a positive double‐blind placebo‐controlled oral food challenge (OFC) also had a positive conjunctival provocation test. None of the children with negative conjunctival provocation test had a positive OFC. The sensitivity and the specificity of the conjunctival provocation test were 0.96 and 0.83, respectively. No children had severe adverse reaction caused by the conjunctival provocation test, whereas 23 children suffered an anaphylactic reaction to the OFC.

Conclusion and Clinical Relevance

Conjunctival allergen challenge appears to be feasible, accurate and safe in diagnosing children referred for suspected peanut allergy.
Is there evidence for a surgeon learning curve for endothelial keratoplasty in Australia?
Authors: Keane Miriam C , Mills Richard AD , Coster Douglas J , Williams Keryn A ,   on behalf of Contributors to the Australian Corneal Graft Registry
Published: February 2017

Importance

Expected outcomes from endokeratoplasty may vary with surgeon experience.

Background

It was explored whether a surgeon learning curve exists for Descemet stripping endothelial keratoplasties (manual or automated) performed in Australia.

Design

This is a prospective cohort study, with various clinical settings.

Participants

There were 2139 recipients of 2615 endothelial grafts, registered by 85 surgeons between January 2006 and December 2013.

Methods

Kaplan–Meier survival analyses and Cox proportional hazards regression were used to examine longitudinal graft survival. Manual and automated Descemet stripping endothelial keratoplasties were analysed together. Pearson chi‐squared analyses were performed to examine differences amongst groups. Continuity correction was used for 2 × 2 tests, and statistical significance was set at P < 0.05 (two‐sided).

Main outcome measure

The main parameter measured was endothelial graft survival.

Results

Survival of the first 56 registered grafts was significantly poorer than survival of subsequent grafts (χ2 = 8.83, df = 1, P = 0.003), when data were combined for all surgeons. Surgeon workload influenced graft survival significantly (P < 0.001). This variable was retained in multivariate analysis designed to investigate independent factors influencing graft survival. Primary non‐functioning grafts were significantly less likely to be reported for endokeratoplasties performed by surgeons with more than 56 registered grafts, compared with those registering 56 or fewer grafts (4.3% vs. 8.5%; χ2 = 18.38, df = 1, P < 0.001).

Conclusions and Relevance

Our findings suggest that for less experienced or low‐volume surgeons, longitudinal graft survival improved once 56 or more endokeratoplasties had been performed, indicative of a learning curve. The learning curve was less apparent for surgeons with 57 or more Descemet stripping endothelial keratoplasties and/or Descemet stripping automated endothelial keratoplasties registered during the 8‐year study period. Different learning curves may be anticipated for these two groups of surgeons.
Higher Anti‐A/B isoagglutinin titers of IgG class, but not of IgM, are associated with increased red blood cell transfusion requirements in bone marrow transplantation with major ABO‐mismatch
Authors: De Santis Gil Cunha , Garcia‐Silva Aline Cristina , Dotoli Giuliana Martinelli , de Castro Pamela Tinti , Simões Belinda Pinto , Covas Dimas Tadeu
Published: February 2017

Background

Major ABO mismatch between donor and recipient in bone marrow transplantation (BMT) may cause hemolysis, delayed red blood cell (RBC) engraftment and pure red cell aplasia (PRCA), which result in increased transfusion needs. High pretransplant anti‐A/B antibody titers have been associated with increased risk of PRCA. Herein, we studied the impact of anti‐A/B titers on transfusion needs after BMT with major ABO mismatch.

Methods

We reviewed the medical charts of 27 patients who underwent to BMT with major ABO mismatch and categorized them into two groups according to anti‐A/B titers of IgG (≤16 and ≥32). We recorded the number of RBC and platelet units transfused in the first 180 days after transplantation. We also evaluated the impact of anti‐A/B titers on overall survival.

Results

Patients with anti‐A/B titer ≥32 of IgG class required more RBC transfusion than patients with titer ≤16 (6.60±4.55 vs 21.29±14.68; P=.03). Anti‐A/B of IgM class had no impact on both RBC and platelet transfusion needs. Anti‐A/B titers had no impact on overall survival.

Conclusion

Higher titers of anti‐A/B antibodies of IgG class, but not of IgM, are associated with a higher demand for RBC transfusion.