bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-322 stabilizes MEK1 expression to inhibit RAF/MEK/ERK pathway activation in cartilage
Authors: Bluhm Björn , Ehlen Harald W. A. , Holzer Tatjana , Georgieva Veronika S. , Heilig Juliane , Pitzler Lena , Etich Julia , Bortecen Toman , Frie Christian , Probst Kristina , Niehoff Anja , Belluoccio Daniele , Van den Bergen Jocelyn , Brachvogel Bent 
Published: August 2017

Cartilage originates from mesenchymal cell condensations that differentiate into chondrocytes of transient growth plate cartilage or permanent cartilage of the articular joint surface and trachea. MicroRNAs fine-tune the activation of entire signaling networks and thereby modulate complex cellular responses, but so far only limited data are available on miRNAs that regulate cartilage development.
Here we characterize a miRNA which promotes the biosynthesis of a key component in the RAF/MEK/ERK pathway in cartilage. Specifically, by transcriptome profiling we identified miR-322 to be upregulated during chondrocyte differentiation. Among the various miR-322 target genes in the RAF/MEK/ERK pathway only Mek1 was identified as a regulated target in chondrocytes. Surprisingly, an increased concentration of miR-322 stabilizes Mek1-mRNA to rise protein levels and dampen ERK1/2 phosphorylation, while cartilage-specific inactivation in mice linked the loss of miR-322 to decreased MEK1 levels and increased RAF/MEK/ERK pathway activation. Such mice died perinatally due to tracheal growth restriction and respiratory failure.
Hence, a single miRNA can stimulate the production of an inhibitory component of a central signaling pathway to impair cartilage development.
Considering aspects of the 3Rs principles within experimental animal biology
Authors: Sneddon Lynne U. , Halsey Lewis G. , Bury Nic R. 
Published: August 2017

ABSTRACT
The 3Rs – Replacement, Reduction and Refinement – are embedded into the legislation and guidelines governing the ethics of animal use in experiments. Here, we consider the advantages of adopting key aspects of the 3Rs into experimental biology, represented mainly by the fields of animal behaviour, neurobiology, physiology, toxicology and biomechanics. Replacing protected animals with less sentient forms or species, cells, tissues or computer modelling approaches has been broadly successful. However, many studies investigate specific models that exhibit a particular adaptation, or a species that is a target for conservation, such that their replacement is inappropriate. Regardless of the species used, refining procedures to ensure the health and well-being of animals prior to and during experiments is crucial for the integrity of the results and legitimacy of the science. Although the concepts of health and welfare are developed for model organisms, relatively little is known regarding non-traditional species that may be more ecologically relevant. Studies should reduce the number of experimental animals by employing the minimum suitable sample size. This is often calculated using power analyses, which is associated with making statistical inferences based on the P-value, yet P-values often leave scientists on shaky ground. We endorse focusing on effect sizes accompanied by confidence intervals as a more appropriate means of interpreting data; in turn, sample size could be calculated based on effect size precision. Ultimately, the appropriate employment of the 3Rs principles in experimental biology empowers scientists in justifying their research, and results in higher-quality science.
The thermal background determines how the infrared and visual systems interact in pit vipers
Authors: Chen Qin , Liu Yang , Brauth Steven E. , Fang Guangzhan , Tang Yezhong 
Published: August 2017

ABSTRACT
The thermal infrared (IR) sensing system of pit vipers is believed to complement vision and provide a substitute imaging system in dark environments. Theoretically, the IR system would best image a scene consisting of a homothermal target in cold surroundings as a bright spot on a dark background. To test this hypothesis, we evaluated how the pit viper (Gloydius brevicaudus) discriminates and strikes prey when the background temperature is either higher or lower than that of the prey (approximately 32–33°C) in different parts of the scene. Snakes were tested in a modified predation cage in which background temperatures were set to 26°C on one side and either 33 or 40°C on the opposite side when the eyes, the pit organs or neither sensory system was occluded. When the eyes were blocked, snakes preferred to strike prey on the 26°C side rather than on the 33°C side but showed no bias in the other conditions. Snakes showed no preference for 26 versus 40°C background temperature, although more missed strikes occurred when the eyes were occluded. The results thus revealed that the pit viper IR system can accomplish a ‘brightness constancy’ computation reflecting the difference between the target and background temperatures, much as the visual system compares the luminance of a figure and the background. Furthermore, the results show that the IR system performs less well for locating prey when the background is warmer than the target.
Pharmacological effects of cannabinoids on learning and memory in Lymnaea
Authors: Sunada Hiroshi , Watanabe Takayuki , Hatakeyama Dai , Lee Sangmin , Forest Jeremy , Sakakibara Manabu , Ito Etsuro , Lukowiak Ken 
Published: August 2017

ABSTRACT
Cannabinoids are hypothesized to play an important role in modulating learning and memory formation. Here, we identified mRNAs expressed in Lymnaea stagnalis central nervous system that encode two G-protein-coupled receptors (Lymnaea CBr-like 1 and 2) that structurally resemble mammalian cannabinoid receptors (CBrs). We found that injection of a mammalian CBr agonist WIN 55,212-2 (WIN 55) into the snail before operant conditioning obstructed learning and memory formation. This effect of WIN 55 injection persisted for at least 4 days following its injection. A similar obstruction of learning and memory occurred when a severe traumatic stimulus was delivered to L. stagnalis. In contrast, injection of a mammalian CBr antagonist AM 251 enhanced long-term memory formation in snails and reduced the duration of the effects of the severe traumatic stressor on learning and memory. Neither WIN 55 nor AM 251 altered normal homeostatic aerial respiratory behaviour elicited in hypoxic conditions. Our results suggest that putative cannabinoid receptors mediate stressful stimuli that alter learning and memory formation in Lymnaea. This is also the first demonstration that putative CBrs are present in Lymnaea and play a key role in learning and memory formation.
The Vehicle Routing Problem with Release and Due Dates
Authors: Shelbourne Benjamin C. , Battarra Maria , Potts Chris N. 
Published: August 2017

A novel extension of the classical vehicle routing and scheduling problems is introduced that integrates aspects of machine scheduling into vehicle routing. Associated with each customer order is a release date that defines the earliest time that the order is available to leave the depot for delivery and a due date that indicates the time by which the order should ideally be delivered to the customer. The objective is to minimize a convex combination of the operational costs and customer service level, represented by the total distance traveled and the total weighted tardiness of delivery, respectively. A path-relinking algorithm (PRA) is proposed to address the problem, and a variety of benchmark instances are generated to evaluate its performance. The PRA exploits the efficiency and aggressive improvement of neighborhood search but relies on a new path-relinking procedure and advanced population management strategies to navigate the search space effectively. To provide a comparator algorithm to the PRA, we embed the neighborhood search into a standard iterated local search algorithm (ILS). Extensive computational experiments on the benchmark instances show that the newly defined features have a significant and varied impact on the problem, and the performance of the PRA dominates that of the ILS algorithm. The online supplement is available at https://doi.org/10.1287/ijoc.2017.0756 .
Investigating the Spillover Effect of Keyword Market Entry in Sponsored Search Advertising
Authors: Lu Shijie , Yang Sha 
Published: August 2017

As Internet advertising infomediaries nowadays provide rich competition information, sponsored search advertisers are becoming more strategic when selecting keywords. This paper empirically examines the spillover effects in advertisers’ keyword market entry decisions, that is, how an advertiser’s likelihood of using a keyword is affected by competitors’ keyword entry decisions. We develop a structural model to characterize advertisers’ keyword market entry decisions. We apply the model to a panel data set of 1,252 laptop-related keywords mainly used by 28 manufacturers, retailers, and comparison websites that advertise on Google. Our analysis leads to several interesting findings. First, an advertiser’s expected position affects the nature of the competition. In particular, the spillover effect from below-ranked competitors is always positive, while the spillover effect from above-ranked competitors is either positive or negative. Second, the spillover effect from above-ranked ads is directionally affected by firms’ product-line characteristics: the effect among firms offering homogenous products (e.g., comparison sites) is negative, whereas the effect among firms with more differentiated products (e.g., manufacturers and retailers) is positive. Third, the spillover effect from above-ranked ads is directionally affected by firms’ positions in a distribution channel: the effect from upstream (downstream) on downstream (upstream) firms tends to be negative (positive). Finally, a downstream firm is more likely to learn new keywords from an upstream firm but not vice versa. Our counterfactual simulations demonstrate that the keyword-specific competition information provided by infomediaries can improve the search engine’s revenue by about 5.7%.Data are available at https://doi.org/10.1287/mksc.2017.1053 .
Discretionary Task Ordering: Queue Management in Radiological Services
Authors: Ibanez Maria R. , Clark Jonathan R. , Huckman Robert S. , Staats Bradley R. 
Published: August 2017

Work scheduling research typically prescribes task sequences implemented by managers. Yet employees often have discretion to deviate from their prescribed sequence. Using data from 2.4 million radiological diagnoses, we find that doctors prioritize similar tasks (batching) and those tasks they expect to complete faster (shortest expected processing time). Moreover, they exercise more discretion as they accumulate experience. Exploiting random assignment of tasks to doctors’ queues, instrumental variable models reveal that these deviations erode productivity. This productivity decline lessens as doctors learn from experience. Prioritizing the shortest tasks is particularly detrimental to productivity. Actively grouping similar tasks also reduces productivity, in stark contrast to productivity gains from exogenous grouping, indicating deviation costs outweigh benefits from repetition. By analyzing task completion times, our work highlights the trade-offs between the time required to exercise discretion and the potential gains from doing so, which has implications for how discretion over scheduling should be delegated. The online appendix is available at https://doi.org/10.1287/mnsc.2017.2810 . This paper was accepted by Serguei Netessine, operations management.
Uncertainty, Capital Investment, and Risk Management
Authors: Doshi Hitesh , Kumar Praveen , Yerramilli Vijay 
Published: August 2017

We use forward-looking and exogenous measures of output price uncertainty to examine the effect of price uncertainty on firm-level capital investment, risk management, and debt issuance. The effects of uncertainty vary significantly by firm size. When faced with high price uncertainty, large firms increase their hedging intensity but do not lower capital investment or debt issuance. In contrast, small firms do not adjust their hedging intensity but significantly lower capital expenditure and debt issuance even after controlling for investment demand. Moreover, the negative effect of uncertainty on capital investment is significantly weaker for firms that hedge their output price risk. Our analysis highlights that, in the presence of financial frictions, high price uncertainty has significant dampening effects on capital investment of small firms by exacerbating their financial constraints, and that this negative effect is amplified by firm-level constraints on ability to hedge risk exposures. The Internet appendix is available at https://doi.org/10.1287/mnsc.2017.2815 . This paper was accepted by Amit Seru, finance.
The BeSMART (Best Supportive Management for Adults Referred with Tonsillopharyngitis) multicentre observational study
Authors: Lau AS , Mamais C , McChesney E , Upile NS , Vaughan C , Veitch J , Abbas JR , Markey A , Brown NG , Evans M , Thomas J , Gaines M , Shehata Z , Wilkie MD , Leong SC 
Published: August 2017

Introduction Tonsillopharyngitis is the most common ear, nose and throat emergency admission, with 80,000 episodes recorded in England in 2015–2016. Despite this, there is a paucity of evidence addressing the supportive management of tonsillopharyngitis in inpatients. The aim of this retrospective multicentre observational study was to consider the Best Supportive Management for Adults Referred with Tonsillopharyngitis (BeSMART) in the inpatient setting, and to establish any associations between practice and outcomes. Methods Seven hospitals in North West England and North East Scotland participated in the study. Overall, 236 adult patients admitted with tonsillopharyngitis were included. The main outcome measures were interval to return to soft diet, length of stay (LOS), pain scores and readmissions. Results Women were more likely to seek professional help before presenting to secondary care (p=0.04). Patients admitted at the weekend were more likely to have a shorter LOS (p=0.03). There was no relationship between day of admission and seniority or specialty of the doctor initially seen. Prescription of corticosteroid, analgesia and a higher initial intravenous fluid infusion rate were not related to a shorter LOS. Conclusions This study is the first to yield valuable insights into the inpatient management of tonsillopharyngitis. This work represents part of an ongoing project to establish the evidence for common medical interventions for sore throat. Patient and professional surveys as well as a prospective interventional study are planned for the future.
Rotator cuff surgery in patients with rheumatoid arthritis: clinical outcome comparable to age, sex and tear size matched non-rheumatoid patients
Authors: Lim SJ , Sun J-H , Kekatpure AL , Chun J-M , Jeon I-H 
Published: August 2017

Aims This study aimed to compare the clinical outcomes of rotator cuff repair in patients with rheumatoid arthritis with those of patients who have no known history of the disease. We hypothesised that the functional outcomes are comparable between patients and without rheumatoid arthritis and may be affected by the level of disease activity, as assessed from C-reactive protein (CRP) level and history of systemic steroid intake. Patients and methods We conducted a retrospective review of the institutional surgical database from May 1995 to April 2012. Twenty-nine patients with rheumatoid arthritis who had rotator cuff repair were enrolled as the study group. Age, sex, and tear size matched patients with no disease who were selected as the control group. The mean duration of follow-up was 46 months (range 24–92 months). Clinical outcomes were assessed with the American Shoulder and Elbow Surgeons (ASES) questionnaire, Constant score and visual analogue scale (VAS). All data were recorded preoperatively and at regular postoperative follow-up visits. CRP was measured preoperatively as the disease activity marker for rheumatoid arthritis. Medication history was thoroughly reviewed in the study group. Results In patients with rheumatoid arthritis, all shoulder functional scores improved after surgery (ASES 56.1–78.1, Constant 50.8–70.5 and VAS 5.2–2.5; P < 0.001). The functional outcome of surgery in patients with rheumatoid arthritis was comparable to that of the control group (difference with control: ASES 78.1 vs. 85.5, P = 0.093; Constant 70.5 vs. 75.9, P = 0.366; VAS 2.5 vs. 1.8, P = 0.108). Patients with rheumatoid arthritis who had an elevated CRP level (> 1 mg/dl) showed inferior clinical outcomes than those with normal CRP levels. Patients with a history of systemic steroid intake showed inferior functional outcomes than those who had not taken steroids. Conclusions Surgical intervention for rotator cuff tear in patients with rheumatoid arthritis improved the shoulder functional outcome comparable to that in matched patients without rheumatoid arthritis. Elevated preoperative CRP level and history of systemic steroid intake portend inferior functional outcome in patients with rheumatoid arthritis.
Safety and effectiveness of antireflux surgery in obese patients
Authors: Tandon A , Rao R , Hotouras A , Nunes QM , Hartley M , Gunasekera R , Howes N 
Published: August 2017

Introduction The incidence of gastro-oesophageal reflux disease and obesity has increased significantly in recent years. The number of antireflux procedures being carried out on people with a higher body mass index (BMI) has been rising. Evidence is conflicting for outcomes of antireflux surgery in obese patients in terms of its safety and efficacy. Given the contradictory reports, this meta-analysis was undertaken to establish the outcomes of antireflux surgery (ARS) in obese patients and its associated safety. Methods A systematic electronic search was conducted using the PubMed, MEDLINE®, Ovid®, Cochrane Library and Google Scholar™ databases to identify studies that analysed the effect of BMI on the outcomes of ARS. A meta-analysis was performed using the random effects model. The intraoperative and postoperative outcomes that were examined included operative time, conversion to an open procedure, mean length of hospital stay, recurrence of acid reflux requiring reoperation and wrap migration. Results A total of 3,772 patients were included in 13 studies. There was no significant difference in procedure conversion rate, recurrence of reflux requiring reoperation or wrap migration between obese and non-obese patients. However, both the mean operative time and mean length of stay were longer for obese patients. Conclusions ARS in obese patients with gastro-oesophageal reflux disease is safe and outcomes are comparable with those in patients with a BMI in the normal range. A high BMI should therefore not be a deterrent to considering ARS for appropriate patients.
Reconstruindo a produção, documentalização e conservação da informação organizacional pré-moderna. Perspetivas teóricas recentes e proposta de percurso de investigação
Authors: De Lurdes Rosa Maria 
Published: August 2017

O artigo nasce de uma experiência de investigação e ensino sobre a história dos arquivos e da informação, centrado na sociedade portuguesa de Antigo Regime. Começa por apresenta as bases da sua construção teórica, oriundas de diferentes disciplinas (História, Ciência da Informação/Ciência Arquivística, Antropologia). Num segundo momento, propõe um percurso de investigação a aplicar às fontes prémodernas, numa perspetiva de história documental das instituições e de aprofundamento da relação entre os recursos heurísticos e a escrita da História.
The Effect of Three Instructional Elements on Achievement in Computer-Based Mathematics Instructions of Senior Secondary School Students in Nigeria
Authors: Omoniyi Tayo , Gbenga Gisanrin 
Published: August 2017

Abstract
This study investigated the effect of three instructional elements on achievement in computer-based mathematics instructions. The subjects were senior secondary school students who used four versions of computer-based instructions developed on compact disc to learn about volume of solid shapes. The four versions of the programme were (1) a full version that had the three instructional elements (2) a version without objective (3) a version without practice (4) a version without examples. Results indicated that the full package, which included objective, practice and examples, had significant effect on students′ achievement in the computer-based mathematics instructions. Furthermore, of the three elements, practice, had the most effect on the learners′ achievement. Implications of the findings on development of computer-based instructions are also discussed.
Effect of Dietary Fish Oil Replacement with Plant Oils on Growth Performance and Gene Expression in Juvenile Rainbow Trout (Oncorhynchus mykiss)
Authors: Kutluyer Filiz , Sirkecioğlu Ahmet Necdet , Aksakal Ercüment , Aksakal Feyza İçoğlu , Tunç Abdullah , Günaydin Esra 
Published: August 2017

Abstract
An eight-week feeding trial was conducted to evaluate the effects of total (100%) replacement of dietary fish oil with alternative lipid sources in juvenile rainbow trout. Six iso-nitrogenous and iso-lipidic experimental diets were formulated: CO (14%) – cod liver oil; SSO (14%) – safflower seed oil; SBO (14%) – soybean oil; LO (14%) – linseed oil; SBO (7%) + LO (7%) – a blend of soybean oil and linseed oil; and SSO (7%) + LO (7%) – a blend of safflower seed oil and linseed oil. Growth performance [specific growth rate (SGR), weight gain (WG), food conversion ratio (FCR) and survival rate (SR)], growth hormones [growth hormone (GH-I), insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II)], immune transforming growth factor-β (TGF-β) and antioxidant [superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and glutathione S-transferase (GST)] response, and heat shock protein 70 (HSP70) mRNA levels were determined in muscle and liver. Our data indicated that final weight, weight gain, FCR and SGR showed significant difference among the six dietary treatments (P<0.05) while there were no significant differences in survival rate between the rainbow trout from supplement fed groups and control group. HSP70 mRNA level expression in muscle was higher in fish fed SSO (P<0.05) while highest level in liver was obtained from fish fed SBO compared to the other treatments (P<0.05). There were no significant differences among treatments for TGF-β mRNA expression level in muscle and liver. In conclusion, growth performance and expression levels of growth hormones, antioxidants, HSP70, except TGF-β were affected by five separate lipid sources. In addition, LO positively increased growth performance of juvenile rainbow trout by means of preventing oxidative stress and HSP70 and, enhanced expression of growth hormone related gene.
Memory-type plate system with nonlinear delay
Authors: Mustafa Muhammad I. 
Published: August 2017

AbstractIn this paper we consider a plate equation with infinite memory in the presence of nonlinear feedbacks with and without delay. Under suitable condition on the weight of the delayed feedback compared with the weight of the non-delayed feedback, we use the energy method to establish an explicit and general decay rate result without imposing restrictive assumptions on the behavior of the relaxation function at infinity.