bluuebunny/crossref_metadata_2025_split huggingface dataset:
AAV Gene Therapy for MPS1-associated Corneal Blindness
Authors: Vance Melisa , Llanga Telmo , Bennett Will , Woodard Kenton , Murlidharan Giridhar , Chungfat Neil , Asokan Aravind , Gilger Brian , Kurtzberg Joanne , Samulski R. Jude , Hirsch Matthew L. 
Published: February 2016

AbstractAlthough cord blood transplantation has significantly extended the lifespan of mucopolysaccharidosis type 1 (MPS1) patients, over 95% manifest cornea clouding with about 50% progressing to blindness. As corneal transplants are met with high rejection rates in MPS1 children, there remains no treatment to prevent blindness or restore vision in MPS1 children. Since MPS1 is caused by mutations in idua, which encodes alpha-L-iduronidase, a gene addition strategy to prevent and potentially reverse, MPS1-associated corneal blindness was investigated. Initially, a codon optimized idua cDNA expression cassette (opt-IDUA) was validated for IDUA production and function following adeno-associated virus (AAV) vector transduction of MPS1 patient fibroblasts. Then, an AAV serotype evaluation in human cornea explants identified an AAV8 and 9 chimeric capsid (8G9) as most efficient for transduction. AAV8G9-opt-IDUA administered to human corneas via intrastromal injection demonstrated widespread transduction, which included cells that naturally produce IDUA and resulted in a >10-fold supraphysiological increase in IDUA activity. No significant apoptosis related to AAV vectors or IDUA was observed under any conditions in both human corneas and MPS1 patient fibroblasts. The collective preclinical data demonstrate safe and efficient IDUA delivery to human corneas, which may prevent and potentially reverse MPS1-associated cornea blindness.
Forests and ozone: productivity, carbon storage and feedbacks
Authors: Wang Bin , Shugart Herman H. , Shuman Jacquelyn K. , Lerdau Manuel T. 
Published: February 2016

AbstractTropospheric ozone is a serious air-pollutant, with large impacts on plant function. This study demonstrates that tropospheric ozone, although it damages plant metabolism, does not necessarily reduce ecosystem processes such as productivity or carbon sequestration because of diversity change and compensatory processes at the community scale ameliorate negative impacts at the individual level. This study assesses the impact of ozone on forest composition and ecosystem dynamics with an individual-based gap model that includes basic physiology as well as species-specific metabolic properties. Elevated tropospheric ozone leads to no reduction of forest productivity and carbon stock and to increased isoprene emissions, which result from enhanced dominance by isoprene-emitting species (which tolerate ozone stress better than non-emitters). This study suggests that tropospheric ozone may not diminish forest carbon sequestration capacity. This study also suggests that, because of the often positive relationship between isoprene emission and ozone formation, there is a positive feedback loop between forest communities and ozone, which further aggravates ozone pollution.
Improving graphene non‐volatile memory using self‐aligned gate
Authors: Lee K. , Kim O. 
Published: February 2016

As the scale of graphene‐based non‐volatile memory is reduced, the ratio of access resistance RA to total channel resistance RTOT is increased. To investigate the effect of the RA on I–V characteristics, we fabricated devices with various access lengths LA and self‐aligned structure. Proposed structure using self‐aligned gate minimises LA, and thereby improves the drain current, ‘on/off’ current ratio ION/IOFF and transfer characteristics. In proposed structure, ‘off’ current is increased from 0.16 to 0.28 mA because RTOT was reduced; ‘on’ current increased from 0.35 to 0.72 mA, but ION/IOFF increased from 2.18 to 2.57. Proposed structure also had larger memory window (8.5 V) than did conventional devices (6.7 V).
B1 propagation properties of combined circularly polarised mode in ultra‐high‐field MRI
Authors: Kim K.‐N. , Seo J.‐H. , Han S.‐D. , Song H. , Ryu Y. 
Published: February 2016

In ultra‐high‐field magnetic resonance imaging (MRI), inhomogeneity of the radiofrequency transmit field (|B1+|) occurs due to wavelength shortening that results from interactions between the coil and the high dielectric subject. Even if a multiple transmit/receive (Tx/Rx) coil array is employed using the first‐order clockwise circularly polarised (|CP1+|) mode, |B1+| inhomogeneity is an insurmountable obstacle. A scheme utilising the CP1+ mode for the odd‐numbered coil elements and the third‐order clockwise CP mode for the even‐numbered coil elements in the multiple‐element Tx/Rx coil array was investigated with the objective of increasing the |B1+| homogeneity at 300 MHz. The results of an electromagnetic simulation and a 7 T MRI experiment are presented and to illustrate the improvements achieved using the optimum CP mode combination is discussed.
Highly conformal polyimide liner deposition in high‐aspect‐ratio through silicon vias
Authors: Ding Yingtao , Yan Yangyang , Xiong Miao , Wang Shiwei , Chen Qianwen , Chen Zhiming 
Published: February 2016

High‐uniformity polyimide liner was successfully achieved in through silicon vias with aspect ratio and density as high as 15:1 and 2.8 × 105/cm2, respectively. The liner is deposited by vacuum‐assisted spin‐coating approach, which used vacuum treatment to fully fill the via followed by spin coating to achieve uniform liner. The uniformity along the sidewall of via is evaluated with cross‐sectional scanning electron microscopy images, and the results show that the thickness along sidewall from top to bottom has an average value of 530 nm and the achieved step coverage is above 33%. This liner deposition approach is completely compatible with complementary metal‐oxide‐ semiconductor (CMOS) processes, and exhibits excellent uniformity, demonstrating the potential of the proposed technique in future advanced three‐dimensional integration applications.
Direct observation of charge re-distribution in a MgB2 superconductor
Authors: Wu Sheng Yun , Shih Po-Hsun , Ji Jhong-Yi , Chan Ting-Shan , Yang Chun Chuen 
Published: February 2016

Abstract
To study the origin of negative thermal expansion effects near the superconducting transition temperature TC in MgB2, low-temperature high-energy synchrotron radiation x-ray diffraction was used to probe the charge redistribution near the boron atoms. Our results reveal that the in-plane hole-distribution of B− hops through the direct orbital overlap of Mg2+ along the c-axis at 50 K and is re-distributed out-of-plane. This study shows that the out-of-plane π-hole distribution plays a dominant role in the possible origin of superconductivity and negative thermal effects in MgB2.
ArabidopsisATHB17 coordinates nuclear and plastidic photosynthesis gene expression in response to abiotic stress
Authors: Zhao Ping , Cui Rong , Xu Ping , Mao Jie-Li , Chen Yu , Zhou Cong-zhao , Yu Lin-Hui , Xiang Cheng-Bin 
Published: February 2016

AbstractPhotosynthesis is sensitive to environmental stresses. How nuclear and plastid genome coordinate to cope with abiotic stress is not well understood. Here we report that ATHB17, anArabidopsisHD-Zip transcription factor, coordinates the expression of nuclear encoded photosynthetic genes (NEPGs) and plastid encoded genes (PEGs) in response to abiotic stress.ATHB17-overexpressing plants display enhanced stress tolerance, whereas its knockout mutant is more sensitive compared to the wild type. Through RNA-seq analysis, we found that ATHB17 down-regulated many NEPGs while up-regulated a number of PEGs. ATHB17 could directly modulate the expression of several NEPGs by binding to their promoters. Furthermore, we identifiedATSIG5, encoding a plastid sigma factor, as one of the target genes of ATHB17. Loss ofATSIG5reduced salt tolerance while overexpression ofATSIG5enhanced salt tolerance, similar to that ofATHB17. Taken together, our results reveal thatATHB17is an important coordinator between NEPGs and PEGs partially through ATSIG5 to protect photosynthesis machinery in response to abiotic stresses.
Des différences, pourquoi? Transmission, maintenance and effects of phenotypic variance
Authors: Plard Floriane , Gaillard Jean‐Michel , Coulson Tim , Tuljapurkar Shripad 
Published: February 2016

Summary

Despite the observed distribution of variable individual phenotypes, survival and reproductive performance in wild populations, models of population dynamics often focus on mean demographic rates. Populations are constituted by individuals with different phenotypes and thus different performances. However, many models of population dynamics provide no understanding of the influence of this phenotypic variation on population dynamics.

In this paper, we investigate how the relationships between demographic rates and phenotype distribution influence the transmission and the upholding of phenotypic variation, and population dynamics. We used integral projection models to measure associations between differences of phenotypic trait (size or mass) among individuals and demographic rates, growth and inheritance, and then quantify the influence of phenotypic variation on population dynamics. We build an analytical and general model resulting from simplifications assuming small phenotypic variance. We illustrate our model with two case studies: a short‐ and a long‐lived life history.

Population growth rate r is determined by a Lotka style equation in which survival and fertility are averaged over a phenotypic distribution that changes with age. Here, we further decomposed r to show how much it is affected by shifts in phenotypic average as well as variance. We derived the elasticities of r to the first and second derivative of each demographic rate. In particular, we show that the nonlinearity of change in selective pressure with phenotype matters more to population dynamics than the strength of this selection. In other words, the variance of a given trait will be most important when the strength of selection increases (or decreases) nonlinearly with that trait.

Inheritance shapes the distribution of newborn phenotypes. Even if newborns have a fixed average phenotype, the variance among newborns increases with phenotypic variance among mothers, strength of inheritance and developmental variation. We explain how the components of inheritance can influence phenotypic variance and thus the demographic rates and population dynamics. In particular, when mothers of different ages produce offspring of different mean phenotype, the inheritance function can have a large influence on both the mean and variance of the trait at different ages and thus on the population growth rate.

We provide new tools to understand how phenotypic variation influences population dynamics and discuss in which life histories we expect this influence to be large. For instance, in our short‐lived life history, individual variability has larger effect than in our long‐lived life history. We conclude by indicating future directions of analysis.
Prioritizing management actions for invasive populations using cost, efficacy, demography and expert opinion for 14 plant species world‐wide
Authors: Kerr Natalie Z. , Baxter Peter W.J. , Salguero‐Gómez Roberto , Wardle Glenda M. , Buckley Yvonne M. 
Published: February 2016

Summary

Management of invasive populations is typically investigated case‐by‐case. Comparative approaches have been applied to single aspects of management, such as demography, with cost or efficacy rarely incorporated.

We present an analysis of the ranks of management actions for 14 species in five countries that extends beyond the use of demography alone to include multiple metrics for ranking management actions, which integrate cost, efficacy and demography (cost‐effectiveness) and managers’ expert opinion of ranks. We use content analysis of manager surveys to assess the multiple criteria managers use to rank management strategies.

Analysis of the matrix models for managed populations showed that all management actions led to reductions in population growth rate (λ), with a median 48% reduction in λ across all management units; however, only 66% of the actions led to declining populations (λ < 1).

Each management action ranked by cost‐effectiveness and cost had a unique rank; however, elasticity ranks were often tied, providing less discrimination among management actions. Ranking management actions by cost alone aligned well with cost‐effectiveness ranks and demographic elasticity ranks were also well aligned with cost‐effectiveness. In contrast, efficacy ranks were aligned with managers’ ranks and managers identified efficacy and demography as important. 80% of managers identified off‐target effects of management as important, which was not captured using any of the other metrics.

Synthesis and applications. A multidimensional view of the benefits and costs of management options provides a range of single and integrated metrics. These rankings, and the relationships between them, can be used to assess management actions for invasive plants. The integrated cost‐effectiveness approach goes well ‘beyond demography’ and provides additional information for managers; however, cost‐effectiveness needs to be augmented with information on off‐target effects and social impacts of management in order to provide greater benefits for on‐the‐ground management.
Local and regional determinants of vascular epiphyte mortality in the Andean mountains of Colombia
Authors: Zuleta Daniel , Benavides Ana M. , López‐Rios Victor , Duque Alvaro 
Published: February 2016

Summary

We present the first large‐scale assessment of vascular epiphyte mortality in the neotropics. Our goals were to explore the primary types of vascular epiphyte death and to identify local and regional determinants of epiphyte mortality in natural forests located 60 to 2900 m a.s.l. in the Colombian Andes.

Based on two consecutive annual surveys, we followed the fate of 4247 epiphytes to estimate the epiphyte mortality rate on 116 host trees at nine sites. A logistic regression analysis for proportional data with a binomial distribution of the error was applied to determine the probability of epiphyte death in relation to local and regional explanatory variables.

The overall epiphyte mortality rate was 7.5 ± 1.1% year−1 (mean ± standard error). Non‐mechanical factors, such as desiccation, accounted for a mortality rate of 1.9 ± 0.3% year−1. Mechanical factors, such as falling branches, accounted for a mortality rate of 5.6 ± 1.1% year−1. According to generalized linear modelling analyses, both local and regional factors played key roles in determining epiphyte mortality. The actual evapotranspiration (regional factor) and the mean epiphyte attachment height (local factor) were both consistently positively associated with the probability of epiphyte death. Additional variables identified as possible determinants of the epiphyte mortality were the temperature seasonality, annual temperature range, the height and number of branches of the tree and the abundance of large trees (DBH ≥10 cm).

Synthesis. The recorded high mortality rate indicates that natural epiphyte assemblages must be highly dynamic to avoid local extinction of species. Our study identifies actual evapotranspiration as an important driver of epiphyte mortality, and we highlight its importance in determining the fate tropical epiphyte communities may experience if evapotranspiration increases due to climate change. We hope our study addresses the paucity of research on non‐tree growth forms, typically ignored in vegetation dynamics, and encourages their inclusion in future studies that investigate the function of tropical ecosystems.
Stage‐dependent effects of exogenous TRAIL on atherogenesis: role of ER stress‐mediated sensitization of macrophage apoptosis
Authors: Liu Fangfang , Cheng Wen , Bi Xiaolei , Zhang Yun , Zhao Yuxia , Jiang Fan 
Published: February 2016

SummaryDeletion of the gene of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) in apolipoprotein E‐deficient (ApoE−/−) mice increased atherosclerosis. However, the effect of TRAIL at a supra‐physiological level on early atherogenesis is unknown. ApoE−/− mice were divided into Early (high‐fat diet with concomitant TRAIL treatment for 4 weeks) and Late (high‐fat diet for 16 weeks with TRAIL being given during the last 4 weeks) groups. It was found that TRAIL stimulated atherogenesis in the Early group but not in the Late group. TRAIL did not change the intra‐plaque macrophage content in Early group, but decreased it in the Late group. In cultured macrophages, induction of endoplasmic reticulum (ER) stress increased death receptor 5 (DR5) expression and TRAIL‐induced apoptosis, which were mediated by the transcription factor CCAAT/enhancer‐binding protein homologous protein (CHOP). The expression levels of CHOP, 78 kDa glucose‐regulated protein (GRP78) and DR5 were all elevated in the Late group. TRAIL treatment in vivo also increased intra‐plaque apoptotic only in Late lesions. Moreover, the chemical chaperone 4‐phenylbutyrate blocked the development of ER stress and upregulation of DR5 in Late lesions in vivo. In conclusion, TRAIL at a supra‐physiological level has a stimulatory effect on early atherogenesis, but not in the advanced lesions. The differential effects of TRAIL may be related to differences in ER stress, DR5 expression, and the sensitivity of macrophage apoptosis in response to TRAIL in early versus advanced lesions. The results presented here raise the possibility that treatment with exogenous TRAIL as a therapeutic agent may be detrimental in patients with increased risk of atherosclerosis.
Using Length of Stay to Control for Unobserved Heterogeneity When Estimating Treatment Effect on Hospital Costs with Observational Data: Issues of Reliability, Robustness, and Usefulness
Authors: May Peter , Garrido Melissa M. , Cassel J. Brian , Morrison R. Sean , Normand Charles 
Published: February 2016

ObjectiveTo evaluate the sensitivity of treatment effect estimates when length of stay (LOS) is used to control for unobserved heterogeneity when estimating treatment effect on cost of hospital admission with observational data.Data Sources/Study SettingWe used data from a prospective cohort study on the impact of palliative care consultation teams (PCCTs) on direct cost of hospital care. Adult patients with an advanced cancer diagnosis admitted to five large medical and cancer centers in the United States between 2007 and 2011 were eligible for this study.Study DesignCosts were modeled using generalized linear models with a gamma distribution and a log link. We compared variability in estimates ofPCCTimpact on hospitalization costs whenLOSwas used as a covariate, as a sample parameter, and as an outcome denominator. We used propensity scores to account for patient characteristics associated with bothPCCTuse and total direct hospitalization costs.Data Collection/Extraction MethodsWe analyzed data from hospital cost databases, medical records, and questionnaires. Our propensity score weighted sample included 969 patients who were discharged alive.Principal FindingsIn analyses of hospitalization costs, treatment effect estimates are highly sensitive to methods that control forLOS, complicating interpretation. Both the magnitude and significance of results varied widely with the method of controlling forLOS. When we incorporated intervention timing into our analyses, results were robust toLOS‐controls.ConclusionsTreatment effect estimates usingLOS‐controls are not only suboptimal in terms of reliability (given concerns over endogeneity and bias) and usefulness (given the need to validate the cost‐effectiveness of an intervention using overall resource use for a sample defined at baseline) but also in terms of robustness (results depend on the approach taken, and there is little evidence to guide this choice). To derive results that minimize endogeneity concerns and maximize external validity, investigators should match and analyze treatment and comparison arms on baseline factors only. Incorporating intervention timing may deliver results that are more reliable, more robust, and more useful than those derived usingLOS‐controls.
Development and Validation of HealthImpact: An Incident Diabetes Prediction Model Based on Administrative Data
Authors: McCoy Rozalina G. , Nori Vijay S. , Smith Steven A. , Hane Christopher A. 
Published: February 2016

ObjectiveTo develop and validate a model of incident type 2 diabetes based solely on administrative data.Data Sources/Study SettingOptum Labs Data Warehouse (OLDW), a national commercial administrative dataset.Study DesignHealthImpact model was developed and internally validated using nested case–control study design; n = 473,049 in training cohort and n = 303,025 in internal validation cohort. HealthImpact was externally validated in 2,000,000 adults followed prospectively for 3 years. Only adults ≥18 years were included.Data Collection/Extraction MethodsPatients with incident diabetes were identified using HEDIS rules. Control subjects were sampled from patients without diabetes. Medical and pharmacy claims data collected over 3 years prior to index date were used to build the model variables.Principal FindingsHealthImpact, scored 0–100, has 48 variables with c‐statistic 0.80815. We identified HealthImpact threshold of 90 as identifying patients at high risk of incident diabetes. HealthImpact had excellent discrimination in external validation cohort (c‐statistic 0.8171). The sensitivity, specificity, positive predictive value, and negative predictive value of HealthImpact >90 for new diagnosis of diabetes within 3 years were 32.35, 94.92, 22.25, and 96.90 percent, respectively.ConclusionsHealthImpact is an efficient and effective method of risk stratification for incident diabetes that is not predicated on patient‐provided information or laboratory tests.
Evolving integral projection models: evolutionary demography meets eco‐evolutionary dynamics
Authors: Rees Mark , Ellner Stephen P. 
Published: February 2016

Summary

Patterns of survival and reproduction determine fitness, and there is a rich body of theory linking demography with evolution. For example, selection analysis can be used to predict changes in trait values, and by approximating selection, equations describing trait dynamics derived and evolutionary endpoints predicted. Here, we provide an overview of how these methods can be used to understand evolutionary dynamics and selection in a structured population modelled by an integral projection model (IPM).

General expressions for selection are given, and we show how these can be approximated using eigenvalue sensitivities. Approximations for the dynamics of both the trait mean and variance are presented and compared to simulation results (IPMs and individual‐based models) for monocarpic perennials.

We describe how selection can be decomposed into components related to survival and reproduction and into components resulting from changes in demography versus changes in population structure. We show that, in an empirically based IPM, effects of changes in population structure can be a major component of the overall selection pressure. Most studies of selection in natural populations have focused entirely on selection due to changes in demography, so our results may help explain why directional selection is often predicted but no evolutionary response is observed.

The endpoints of evolution, what we expect to see in nature, are explored using ideas from adaptive dynamics theory. The key methods are based on evolutionarily stable strategies (ESS) and convergence stability. Efficient methods for finding an ESS are described. We then extend these ideas to function‐valued traits, where it is assumed that an entire function can evolve, rather than a few parameters defining it.

By combining theory for IPMs with ideas from several different fields, we show how the dynamics of ecologically complex, evolving systems can be understood.