bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resource constraints highlight complex microbial interactions during lake biofilm development
Authors: Wyatt Kevin H. , Seballos Rody C. , Shoemaker Maria N. , Brown Shawn P. , Chandra Sudeep , Kuehn Kevin A. , Rober Allison R. , Sadro Steven 
Published: June 2019

Abstract

This study evaluated how the availability of nutrients and organic carbon interact to influence the associations between autotrophic and heterotrophic micro‐organisms during lake biofilm development. Considering that decomposers are often better competitors for nutrients than producers in aquatic environments, we hypothesized that heterotrophs would outcompete autotrophs for available nutrients unless heterotrophs were limited by organic carbon provided by autotrophs.

To test our hypothesis, we evaluated autotrophic (algae) and heterotrophic (fungi, bacteria) biomass in response to a factorial enrichment of nutrients (nitrogen and phosphorus in combination) and glucose using nutrient‐diffusing substrates with either inorganic or organic discs in a subalpine lake. In the field, nutrient‐diffusing substrates were exposed to either natural sunlight or placed under a darkened experimental canopy to evaluate the response of heterotrophs to nutrients and carbon subsidies in the presence or absence of algae. We expected that heterotrophs would be limited by organic carbon on inorganic substrates in the absence of autotrophic production (i.e., dark treatments), and that organic substrates would provide a carbon subsidy for heterotrophic metabolism.

Fungi were stimulated by nutrient enrichment on inorganic substrates in the presence of algae (light treatment), but not in the dark (without algae). The response of fungi to algal presence on inorganic substrates was similar in magnitude to the response of fungi to nutrients and glucose substrates incubated in the dark. In contrast to our expectations, elevated algal biomass did not stimulate heterotrophic bacteria in the presence of elevated nutrient levels on inorganic substrates, possibly owing to antagonistic interactions between bacteria and fungi.

The positive effect of nutrients on algal biomass was significantly reduced in favour of heterotrophs when nutrients were combined with glucose, suggesting that heterotrophs were able to outcompete algae for available nutrients in the absence of carbon limitation.

Synthesis. These results expand our understanding of how the availability of limiting resources governs the outcomes of complex interactions among micro‐organisms in aquatic biofilms, and suggests that background levels of organic carbon regulate producer and decomposer responses to nutrient availability during biofilm development.
Measuring the Trade Restrictiveness of Domestic Support using the EU Common Agricultural Policy as an Example
Authors: Boysen‐Urban Kirsten , Brockmeier Martina , Jensen Hans G. , Boysen Ole 
Published: June 2019

AbstractWe develop an index that measures the overall trade effects of domestic support payments. Our index is based on the Mercantilist Trade Restrictiveness Index (MTRI) and is capable of analysing the development of the trade restrictiveness of domestic support payments over time and across countries. It facilitates the evaluation of agricultural policy reforms introducing changes in the composition of domestic support payments. We conduct this analysis with a computable general equilibrium model that is extended to depict detailed agricultural policies using the Common Agricultural Policy of the European Union (EU) as an example. For the representation of agricultural policies, we updated the underlying database by incorporating detailed EU domestic support payments taken from the OECD Producer Support Estimate (PSE) tables and reconcile PSE data with the WTO classification scheme. Our index confirms a decrease in trade distortion stemming from the implementation of decoupled support in the EU. In addition, the trade‐equivalent protection rate shows that the trade restrictiveness of domestic support payments depends on the assumptions made with regard to the degree of decoupling of those payments.
Analysing continuous proportions in ecology and evolution: A practical introduction to beta and Dirichlet regression
Authors: Douma Jacob C. , Weedon James T. 
Published: June 2019

Abstract

Proportional data, in which response variables are expressed as percentages or fractions of a whole, are analysed in many subfields of ecology and evolution. The scale‐independence of proportions makes them appropriate to analyse many biological phenomena, but statistical analyses are not straightforward, since proportions can only take values from zero to one and their variance is usually not constant across the range of the predictor. Transformations to overcome these problems are often applied, but can lead to biased estimates and difficulties in interpretation.

In this paper, we provide an overview of the different types of proportional data and discuss the different analysis strategies available. In particular, we review and discuss the use of promising, but little used, techniques for analysing continuous (also called non‐count‐based or non‐binomial) proportions (e.g. percent cover, fraction time spent on an activity): beta and Dirichlet regression, and some of their most important extensions.

A major distinction can be made between proportions arising from counts and those arising from continuous measurements. For proportions consisting of two categories, count‐based data are best analysed using well‐developed techniques such as logistic regression, while continuous proportions can be analysed with beta regression models. In the case of >2 categories, multinomial logistic regression or Dirichlet regression can be applied. Both beta and Dirichlet regression techniques model proportions at their original scale, which makes statistical inference more straightforward and produce less biased estimates relative to transformation‐based solutions. Extensions to beta regression, such as models for variable dispersion, zero‐one augmented data and mixed effects designs have been developed and are reviewed and applied to case studies. Finally, we briefly discuss some issues regarding model fitting, inference, and reporting that are particularly relevant to beta and Dirichlet regression.

Beta regression and Dirichlet regression overcome some problems inherent in applying classic statistical approaches to proportional data. To facilitate the adoption of these techniques by practitioners in ecology and evolution, we present detailed, annotated demonstration scripts covering all variations of beta and Dirichlet regression discussed in the article, implemented in the freely available language for statistical computing, r.
The selective FKBP51 inhibitor SAFit2 reduces alcohol consumption and reinstatement of conditioned alcohol effects in mice
Authors: König Loretta , Kalinichenko Liubov S. , Huber Sabine E. , Voll Andreas M. , Bauder Michael , Kornhuber Johannes , Hausch Felix , Müller Christian P. 
Published: June 2019

AbstractThere is still no widely effective pharmacotherapy for alcohol addiction available in the clinic. FK506‐binding protein 51 (FKBP51) is a negative regulator of the glucocorticoid receptor signaling pathway that regulates the stress‐induced glucocorticoid feedback circuit. Here we asked whether selective inhibitors of FKBP51, exemplified by SAFit2, may serve as a new pharmacological strategy to reduce alcohol consumption and conditioned alcohol effects in a mouse model. We report that a relatively short treatment with SAFit2 (20 mg/kg, ip) reduces ongoing 16 vol% alcohol consumption when administered during free access to alcohol in a two‐bottle free‐choice test. SAFit2 was also able to reduce alcohol consumption when given during an abstinence period immediately before relapse. In contrast, SAFit2 did not affect alcohol consumption when given during a relapse period after repeated withdrawal from alcohol. SAFit2 (10 and 20 mg/kg, ip) showed no effects when used in an intermittent drinking schedule. When 20 vol% alcohol was only available every other day, SAFit2 had no effect on drinking, no matter whether given during a drinking episode or the day before. SAFit2 (2 and 20 mg/kg, ip) did not affect the expression of an alcohol‐induced conditioned place preference (CPP). However, SAFit2 was able to inhibit alcohol‐induced reinstatement of an extinguished CPP in a dose‐dependent way. Altogether, these data may suggest pharmacological inhibition of FKBP51 as a viable strategy to reduce alcohol seeking and consumption.
BBS5 and INPP5E mutations associated with ciliopathy disorders in families from Pakistan
Authors: Khan Shazia , Lin Siying , Harlalka Gaurav V. , Ullah Asmat , Shah Khadim , Khalid Sumbul , Mehmood Sarmad , Hassan Muhammad Jawad , Ahmad Wasim , Self Jay E. , Crosby Andrew H. , Baple Emma L. , Gul Asma 
Published: June 2019

AbstractCiliopathies are a clinically and genetically heterogeneous group of disorders often exhibiting phenotypic overlap and caused by abnormalities in the structure or function of cellular cilia. As such, a precise molecular diagnosis is important for guiding clinical management and genetic counseling. In the present study, two Pakistani families comprising individuals with overlapping clinical features suggestive of a ciliopathy syndrome, including intellectual disability, obesity, congenital retinal dystrophy, and hypogonadism (in males), were investigated clinically and genetically. Whole‐exome sequencing identified the likely causes of disease as a novel homozygous frameshift mutation (NM_152384.2: c.196delA; p.(Arg66Glufs*12); family 1) in BBS5, and a nonsense mutation (NM_019892.5:c.1879C>T; p.Gln627*; family 2) in INPP5E, previously reported in an extended Pakistani family with MORM syndrome. Our findings expand the molecular spectrum associated with BBS5 mutations in Pakistan and provide further supportive evidence that the INPP5E mutation is a common cause of ciliopathy in Northern Pakistan, likely representing a regional founder mutation. This study also highlights the value of genomic studies in Pakistan for families affected by rare heterogeneous developmental disorders and where clinical phenotyping may be limited by geographical and financial constraints. The identification of the spectrum and frequency of disease‐causing variants within this setting enables the development of population‐specific genetic testing strategies targeting variants common to the local population and improving health care outcomes.
Effects of CYP3A inhibitors on the pharmacokinetics of quizartinib, a potent and selective FLT3 inhibitor, and its active metabolite
Authors: Li Jianke , Kankam Martin , Trone Denise , Gammon Guy 
Published: June 2019

AimsQuizartinib is an oral, highly potent and selective next‐generation FMS‐like tyrosine kinase 3 (FLT3) inhibitor under investigation in patients with FLT3‐internal tandem duplication‐mutated acute myeloid leukaemia. This drug–drug interaction study assessed the pharmacokinetics (PK) of quizartinib when coadministered with strong or moderate cytochrome P450 3A (CYP3A) inhibitors.MethodsIn this parallel‐group study, subjects were randomised to receive: (i) quizartinib + ketoconazole; (ii) quizartinib + fluconazole; or (iii) quizartinib alone. On Days 1–28, subjects received ketoconazole 200 mg or fluconazole 200 mg twice daily, and on Day 8, all subjects received a single 30‐mg quizartinib dose. Blood samples were collected for PK analyses, steady‐state PK parameters were simulated by superpositioning, and safety was assessed.ResultsNinety‐three healthy subjects were randomised; 86 completed the study. When administered with ketoconazole, geometric mean ratios (90% confidence interval) for quizartinib maximum observed plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) from time 0 extrapolated to infinity were 117% (105%, 130%) and 194% (169%, 223%), respectively, vs quizartinib alone. Steady‐state PK simulation demonstrated ~2‐fold increase of both steady–state Cmax and AUC from time 0 to the end of the dosing interval when quizartinib was administered with ketoconazole due to accumulation of quizartinib at steady state. When administered with fluconazole, geometric mean ratios (90% confidence interval) for quizartinib Cmax and AUC from time 0 extrapolated to infinity were 111% (100%, 124%) and 120% (104%, 138%), respectively, vs quizartinib alone. Overall, 5.4% of subjects experienced quizartinib‐related adverse events; no serious adverse events or deaths occurred.ConclusionsThese results suggest reducing the dose of quizartinib when coadministered with a strong CYP3A inhibitor, but not with a moderate or weak CYP3A inhibitor. This dose reduction was implemented in phase 3 evaluation of quizartinib.
Hierarchical Rasterization of Curved Primitives for Vector Graphics Rendering on the GPU
Authors: Dokter Mark , Hladky Jozef , Parger Mathias , Schmalstieg Dieter , Seidel Hans‐Peter , Steinberger Markus 
Published: June 2019

AbstractIn this paper, we introduce the CPatch, a curved primitive that can be used to construct arbitrary vector graphics. A CPatch is a generalization of a 2D polygon: Any number of curves up to a cubic degree bound a primitive. We show that a CPatch can be rasterized efficiently in a hierarchical manner on the GPU, locally discarding irrelevant portions of the curves. Our rasterizer is fast and scalable, works on all patches in parallel, and does not require any approximations. We show a parallel implementation of our rasterizer, which naturally supports all kinds of color spaces, blending and super‐sampling. Additionally, we show how vector graphics input can efficiently be converted to a CPatch representation, solving challenges like patch self intersections and false inside‐outside classification. Results indicate that our approach is faster than the state‐of‐the‐art, more flexible and could potentially be implemented in hardware.
Object Partitioning for Support‐Free 3D‐Printing
Authors: Karasik E. , Fattal R. , Werman M. 
Published: June 2019

AbstractFused deposition modeling based 3D‐printing is becoming increasingly popular due to it's low‐cost and simple operation and maintenance. While it produces rugged prints made from a wide range of materials, it suffers from an inherent printing limitation where it cannot produce overhanging surfaces of non‐trivial size. This limitation can be handled by constructing temporary support‐structures, however this solution involves additional material costs, longer print time, and often a fair amount of labor in removing it.In this paper we present a new method for partitioning general solid objects into a small number of parts that can be printed with no support. The partitioning is computed by applying a sequence of cutting‐planes that split the object recursively. Unlike existing algorithms, the planes are not chosen at random, rather they are derived from shape analysis routines that identify and resolve various commonly‐found geometric configurations. In addition, we guide this search by a revised set of conditions that both ensure the objects' printability as well as realistically model the printing capabilities of the printer at hand.Evaluation of the new method demonstrates its ability to efficiently obtain support‐free partitionings typically containing fewer parts compared to existing methods that rely on support‐structures.
Latent‐space Dynamics for Reduced Deformable Simulation
Authors: Fulton Lawson , Modi Vismay , Duvenaud David , Levin David I. W. , Jacobson Alec 
Published: June 2019

AbstractWe propose the first reduced model simulation framework for deformable solid dynamics using autoencoder neural networks. We provide a data‐driven approach to generating nonlinear reduced spaces for deformation dynamics. In contrast to previous methods using machine learning which accelerate simulation by approximating the time‐stepping function, we solve the true equations of motion in the latent‐space using a variational formulation of implicit integration. Our approach produces drastically smaller reduced spaces than conventional linear model reduction, improving performance and robustness. Furthermore, our method works well with existing force‐approximation cubature methods.
Exploratory Stage Lighting Design using Visual Objectives
Authors: Shimizu Evan , Paris Sylvain , Fisher Matt , Yumer Ersin , Fatahalian Kayvon 
Published: June 2019

AbstractLighting is a critical element of theater. A lighting designer is responsible for drawing the audience's attention to a specific part of the stage, setting time of day, creating a mood, and conveying emotions. Designers often begin the lighting design process by collecting reference visual imagery that captures different aspects of their artistic intent. Then, they experiment with various lighting options to determine which ideas work best on stage. However, modern stages contain tens to hundreds of lights, and setting each light source's parameters individually to realize an idea is both tedious and requires expert skill. In this paper, we describe an exploratory lighting design tool based on feedback from professional designers. The system extracts abstract visual objectives from reference imagery and applies them to target regions of the stage. Our system can rapidly generate plausible design candidates that embody the visual objectives through a Gibbs sampling method, and present them as a design gallery for rapid exploration and iterative refinement. We demonstrate that the resulting system allows lighting designers of all skill levels to quickly create and communicate complex designs, even for scenes containing many color‐changing lights.
Practical Person‐Specific Eye Rigging
Authors: Bérard P. , Bradley D. , Gross M. , Beeler T. 
Published: June 2019

AbstractWe present a novel parametric eye rig for eye animation, including a new multi‐view imaging system that can reconstruct eye poses at submillimeter accuracy to which we fit our new rig. This allows us to accurately estimate person‐specific eyeball shape, rotation center, interocular distance, visual axis, and other rig parameters resulting in an animation‐ready eye rig. We demonstrate the importance of several aspects of eye modeling that are often overlooked, for example that the visual axis is not identical to the optical axis, that it is important to model rotation about the optical axis, and that the rotation center of the eye should be measured accurately for each person. Since accurate rig fitting requires hand annotation of multi‐view imagery for several eye gazes, we additionally propose a more user‐friendly “lightweight” fitting approach, which leverages an average rig created from several pre‐captured accurate rigs. Our lightweight rig fitting method allows for the estimation of eyeball shape and eyeball position given only a single pose with a known look‐at point (e.g. looking into a camera) and few manual annotations.
Near‐Eye Display and Tracking Technologies for Virtual and Augmented Reality
Authors: Koulieris G. A. , Akşit K. , Stengel M. , Mantiuk R. K. , Mania K. , Richardt C. 
Published: June 2019

AbstractVirtual and augmented reality (VR/AR) are expected to revolutionise entertainment, healthcare, communication and the manufacturing industries among many others. Near‐eye displays are an enabling vessel for VR/AR applications, which have to tackle many challenges related to ergonomics, comfort, visual quality and natural interaction. These challenges are related to the core elements of these near‐eye display hardware and tracking technologies. In this state‐of‐the‐art report, we investigate the background theory of perception and vision as well as the latest advancements in display engineering and tracking technologies. We begin our discussion by describing the basics of light and image formation. Later, we recount principles of visual perception by relating to the human visual system. We provide two structured overviews on state‐of‐the‐art near‐eye display and tracking technologies involved in such near‐eye displays. We conclude by outlining unresolved research questions to inspire the next generation of researchers.
Effects of alpha‐cyclodextrin on cholesterol control and Compound K on glycaemic control in people with pre‐diabetes: Protocol for a Phase III randomized controlled trial
Authors: Bessell Erica , Fuller Nicholas R. , Markovic Tania P. , Burk Jessica , Picone Tegan , Hendy Chelsea , Tan Michelle M. C. , Caterson Ian D. 
Published: June 2019

SummaryThe prevalence of pre‐diabetes and of type 2 diabetes mellitus is increasing. Preventing disease progression is important to improve outcomes. Natural products are becoming popular alternatives to pharmaceutical products for preventative health and treatment of disease; however, the evidence to support the use of natural alternatives for pre‐diabetes and type 2 diabetes is lacking. Two such natural medicines include alpha‐cyclodextrin (marketed as FBCx), a fibre derived from corn starch that has been found to bind triglycerides in the intestines to prevent its absorption, aiding weight maintenance and lipid control, and hydrolysed ginseng extract (marketed as GINST15), a formula containing high amounts of Compound K, a metabolite of ginsenosides thought to be an active ingredient contributing to the anti‐hyperglycaemic effects of ginseng. This paper describes the rationale and design of a 12‐month randomized controlled trial to investigate the metabolic effects of these two products in people with pre‐diabetes and overweight or obesity. A total of 400 participants will be randomized to one of four groups (FBCx + GINST15, FBCx + placebo, placebo + GINST15, placebo + placebo) for 6 months, followed by 6 months of follow‐up. Participants will also receive lifestyle advice for healthy eating and weight loss. Data collected during the trial will include weight, waist circumference, body composition and blood pressure. Blood samples will also be collected to measure lipid profile and glycaemia. If the products are found to improve lipid and glucose levels, it will provide evidence for their use in people with pre‐diabetes to help reduce the risk of progression to type 2 diabetes.