bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral health in pregnancy: educational needs of dental professionals and office staff
Authors: Kloetzel Megan K. , Huebner Colleen E. , Milgrom Peter , Littell Christopher T. , Eggertsson Hafsteinn
Published: April 2012

Objective: Dental care during pregnancy is important for pregnant women and their children. Comprehensive guidelines for the provision of dental services for pregnant patients were published in 2006, but there is relatively little information about their use in actual practice. The aim of this study was to examine differences in knowledge and attitudes regarding dental care in pregnancy among dentists, dental hygienists, dental assistants, and nonclinical office staff. A secondary aim was to identify sources of influence on attitudes and knowledge regarding the guidelines.

Methods: A survey was used to collect information from 766 employees of a Dental Care Organization based in Oregon; responses from 546 were included in the analyses reported here.

Results: Statistically significant differences in knowledge were found among the professional‐role groups. Dentists and hygienists consistently answered more items correctly than did other respondents. Within all professional‐role groups, knowledge gaps existed and were most pronounced regarding provision of routine and emergency services. Positive perceptions of providing dental care during pregnancy were associated with higher knowledge scores (z = 4.16, P < 0.001).

Conclusions: Updated dental education and continuing education for all dental office personnel are needed to promote the diffusion of current evidence‐based guidelines for dental care during pregnancy.
Factors associated with mutans streptococci among young WIC‐enrolled children
Authors: Weber‐Gasparoni Karin , Goebel Bryce M. , Drake David R. , Kramer Katherine W.O. , Warren John J. , Reeve Johnmarshall , Dawson Deborah V.
Published: April 2012

Objectives: The objective of this study is to assess relationships between the presence or absence of mutans streptococci (MS) and other covariates in children aged 12‐49 months.

Methods: Data were analyzed using baseline information from 411 children enrolled in the Special Supplemental Food Program for Women, Infants and Children (WIC) who participated in a psychoeducational study in Iowa. Children were assessed for MS using a semiquantitative method (RODAC plates). Dental examinations using d1d2.3 criteria and presence of visible plaque on incisors and molars were completed. Mothers completed a series of detailed questionnaires regarding their child's oral health, their socioeconomic status, their child's dietary/oral hygiene habits, and beverage consumption, among other behaviors. Bivariate relationships with the presence of MS were assessed and followed by multivariable modeling using logistic regression (alpha = 0.05).

Results: MS was present in 144 children (35 percent). Bivariate relationships with MS presence were identified for multiple covariates that included demographic characteristics, type of beverage consumption, dental caries, and plaque measures. Multivariate logistic regression modeling suggested that MS presence in children was positively associated with nonwhite race of the child, number of teeth present, presence of cavitated lesions, proportion of teeth with plaque, and lower levels of maternal education.

Conclusions: The presence of MS was associated with greater caries and plaque scores and with low maternal education and nonwhite racial background.
COVER: a priori estimation of coverage for metagenomic sequencing
Authors: Tamames Javier , de la Peña Santiago , de Lorenzo Victor
Published: April 2012

In any metagenomic project, the coverage obtained for each particular species depends on its abundance. This makes it difficult to determine a priori the amount of DNA sequencing necessary to obtain a high coverage for the dominant genomes in an environment. To aid the design of metagenomic sequencing projects, we have developed COVER, a web‐based tool that allows the estimation of the coverage achieved for each species in an environmental sample. COVER uses a set of 16S rRNA sequences to produce an estimate of the number of operational taxonomic units (OTUs) in the sample, provides a taxonomic assignment for them, estimates their genome sizes and, most critically, corrects for the number of unobserved OTUs. COVER then calculates the amount of sequencing needed to achieve a given goal. Our tests and simulations indicate that the results obtained through COVER are in very good agreement with the experimental results.
Liver analysis using gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid‐enhanced magnetic resonance imaging: Correlation with histological grading and quantitative liver evaluation prior to hepatectomy
Authors: Kumazawa Keigo , Edamoto Yoshihiro , Yanase Mikio , Nakayama Tomohiro
Published: April 2012

Aim:  To examine the effectiveness of gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (MRI) in the assessment of parenchymal liver fibrosis and quantitative liver function prior to hepatectomy.

Methods:  Between July 2008 and September 2011, the data of 93 consecutive patients undergoing preoperative Gd‐EOB‐DTPA‐enhanced MRI were analyzed, including serum fibrosis marker levels (hyaluronic acid, type IV collagen), 15‐min retention rates of indocyanine green (ICG‐R15) in the ICG clearance test, and technetium‐99m galactosyl serum albumin scintigraphy results. Liver intensity values were obtained by calculating the differences between the intensity of the liver and that of other organs in the hepatobiliary phase. Degrees of liver fibrosis were quantitatively assessed (F0–4). MRI data were correlated with the prospectively acquired clinical data.

Results:  Varying degrees of liver fibrosis were detected in 31 of the 93 patients. The intensity ratio of the liver to spinal cord on MRI negatively correlated with hepatic fibrosis (R = −0.479, P < 0.001) and ICG‐R15 (R = −0.492, P < 0.001). When patients with F0–2 (normal/moderate) and F3–4 (severe) liver fibrosis were compared, the intensity ratio of the enhanced liver to spinal cord (IRLS) on MRI was significantly lower in the F3–4 group than in the F0–2 group. IRLS was correlated with liver fibrosis, and, when an IRLS criterion of less than 1.702 was used, severe liver fibrosis could be predicted with 68.8% sensitivity and 93.5% specificity.

Conclusion:  Preoperative Gd‐EOB‐DTPA‐enhanced MRI analysis can detect quantitative indicators of liver fibrosis and function, thus aiding the assessment of hepatic remnants prior to hepatectomy.
Development of specific and quantitative real‐time detection PCR and immunoassays for λ3‐interferon
Authors: Sugiyama Masaya , Kimura Tatsuji , Naito Shigeko , Mukaide Motokazu , Shinauchi Takanori , Ueno Masakatsu , Ito Kiyoaki , Murata Kazumoto , Mizokami Masashi
Published: April 2012

Aim:  Single nucleotide polymorphisms (SNP) around interferon (IFN)‐λ3 have been associated with the response to pegylated IFN‐α treatment for chronic hepatitis C. Specific quantification methods for IFN‐λ3 are required to facilitate clinical and basic study.

Methods:  Gene‐specific primers and probes for IFN‐λ1, 2 and 3 were designed for real‐time detection PCR (RTD–PCR). Dynamic range and specificity were examined using specific cDNA clones. Total RNA from hematopoietic and hepatocellular carcinoma cell lines was prepared for RTD–PCR. Monoclonal antibodies were developed for the IFN‐λ3‐specific immunoassays. The immunoassays were assessed by measuring IFN‐λ3 in serum and plasma.

Results:  The RTD–PCR had a broad detection range (10–107 copies/assay) with high specificity (∼107‐fold specificity). Distinct expression profiles were observed in several cell lines. Hematopoietic cell lines expressed high levels of IFN‐λ compared with hepatocellular carcinoma cells, and Sendai virus infection induced strong expression of IFN‐λ. The developed chemiluminescence enzyme immunoassays (CLEIA) detected 0.1 pg/mL of IFN‐λ3 and showed a wide detection range of 0.1–10 000 pg/mL with little or no cross‐reactivity to IFN‐λ1 or IFN‐λ2. IFN‐λ3 could be detected in all the serum and plasma samples by CLEIA, with median concentrations of 0.92 and 0.86 pg/mL, respectively.

Conclusion:  Our newly developed RTD–PCR and CLEIA assays will be valuable tools for investigating the distribution and functions of IFN‐λ3, which is predicted to be a marker for predicting outcome of therapy for hepatitis C or other virus diseases.
Evaluation of a novel non‐invasive 13C‐glucose breath test for the identification of diabetes mellitus in cirrhotic patients
Authors: Tsuchiya Masako , Yamasaki Takahiro , Sakaida Isao
Published: April 2012

Aim:  Diabetes mellitus (DM) has been reported to worsen the long‐term prognosis of cirrhotic patients, and many studies have reported that DM is an independent risk factor for hepatocellular carcinoma. However, an accurate diagnosis of DM is sometimes difficult in cirrhotic patients. Recently, a novel non‐invasive 13C‐glucose breath test has been reported to be useful for diagnosing insulin resistance in non‐cirrhotic patients. The aim of this study was to evaluate the efficacy of this tool for the identification of DM in cirrhotic patients.

Methods:  Thirty eight cirrhotic patients with normal fasting serum glucose and hemoglobin A1c levels underwent the 13C‐glucose breath test and the oral glucose tolerance test. Blood and breath samples were collected at baseline and at 30, 60 and 120 min after ingestion of 100 mg 13C‐labeled glucose and 75 g glucose.

Results:  There was a strong correlation between the change in the concentrations at 2 h for the measured 13C‐glucose breath test (2h‐BT) and the 2 h plasma glucose level (r = −0.60, P < 0.0001). In a receiver–operator curve analysis using the 2h‐BT, the area under the curve was determined to be 0.88, with a sensitivity and specificity (cut‐off value of 3.5‰) of 82% and 85%, respectively, for the detection of DM. Multivariate analysis showed the 2h‐BT to be an independent parameter to identify DM.

Conclusion:  The 13C‐glucose breath test is a useful tool and has the potential to become a routine outpatient examination for the screening of DM in cirrhotic patients.
Commercialization of Platform Technologies: Launch Timing and Versioning Strategy
Authors: Bhargava Hemant K. , Kim Byung Cho , Sun Daewon
Published: April 2012

Many emerging entrepreneurial applications and services connect two or more groups of users over Internet‐based information technologies. Commercial success of such technology products requires astute business practices related to product line design, price discrimination, and launch timing. We examine these issues for a platform firm that serves two markets—labeled as user and developer markets—such that the size of each market positively impacts participation in the other. In addition, our model allows for sequential unfolding of consumer and developer participation, and for uncertainty regarding developer participation. We demonstrate that product versioning is an especially attractive strategy for platform firms, that is, the trade‐off between market size and margins is tilted in the direction of more versions. However, when expanding the product line carries substantial fixed costs (e.g., marketing cost, cost of additional plant, increased distribution cost), then the uncertainty in developer participation adversely impacts the firm's ability to offer multiple versions. We show that for established firms with lower uncertainty about developer participation, the choice is essentially between an expanded or minimal product line. Startups and firms that are entering a new product category are more likely to benefit from a “wait and see” deferred expansion strategy.
Suicidal Ideation in Anxiety‐Disordered Youth
Authors: O’Neil Kelly A. , Puleo Connor M. , Benjamin Courtney L. , Podell Jennifer L. , Kendall Philip C.
Published: April 2012

Evidence is mixed regarding an independent association between anxiety and suicidality in youth. Study 1 examined suicidal ideation in treatment‐referred, anxiety‐disordered youth (N = 312, aged 7–17). Forty‐one percent of anxiety‐disordered youth endorsed suicidal ideation. Anxiety disorder severity, global impairment, and current depressive symptoms predicted suicidal ideation in a multivariate model. Study 2 compared youth (N = 216, aged 7–14) with and without anxiety disorders. Higher rates of suicidal ideation were associated with anxiety diagnosis, and levels of anxiety predicted suicidal ideation after controlling for comorbid depressive disorders, current depressive symptoms, and global impairment. Results support an association between anxiety disorders and suicidal ideation in treatment‐referred youth and recommend routine screening for suicidal ideation in this population.
The Effects of Executive Stock Options and Stock Bonuses on Payout Policies in Taiwan
Authors: Chan Chia‐Ying , Tai Vivian W. , Chan Chi‐Hung , Li Kuo‐An
Published: April 2012

This study investigates how executive stock‐based compensation affects the payout policies of a company. Stock bonuses, which are dividend‐protected, induce executives to pay out cash dividends. Conversely, stock options, which are not dividend‐protected, discourage the payment of dividends. We posit that the structure of executive stock‐based compensation plays a crucial role in determining the payout policies of a firm, particularly for those firms with higher percentages of institutional investors and shareholders with ultimate controlling power. We further examine the effects of the 2008 stock option expensing policy reform in Taiwan as well as the repercussions, if any, that this policy had on payout choices in 2009. The empirical results not only indicate that executive stock‐based compensation has a conspicuous influence on the payout policies of a firm, but also that there is a positive relation between stock bonuses and cash dividends. Furthermore, in the case of Taiwan, which has a relatively low corporate income tax rate, firms with higher percentages of shareholders with ultimate controlling power have less preference to pay cash dividends and greater preference to retain profits within the company.
The Effects of Outside Board on Firm Value in the Emerging Market from the Perspective of Information Transaction Costs*
Authors: Joh Sung Wook , Jung Jin‐Young
Published: April 2012

This paper examines whether the problem of high information asymmetry lowers the positive impact of board independence on firm value. Independent directors are outside directors who have never had business and professional ties with the firm. We adopt various proxies for information transaction costs from the market microstructure literature and traditional measures, such as firm size, firm age, number of analyst reports, governance scores, credit ratings, and institutional ownership, to see how they interact. Using data on publicly listed firms and their directors between 1999 and 2006 in Korea, we find that independent directors are correlated with higher corporate value when the firm has lower information transaction costs. The results suggest that the monitoring role of independent directors is limited when transferring firm‐specific information is costly.
Effect of potential therapeutic agents in reducing oxidative stress in pulmonary tissues of recurrent airway obstruction‐affected and clinically healthy horses
Authors: VENUGOPAL C. , MARIAPPAN N. , HOLMES E. , KEARNEY M. , BEADLE R.
Published: April 2012

Reasons for performing study:To determine and compare the reactive oxygen and nitrogen species (ROS and RNS) in pulmonary tissues of horses affected with recurrent airway obstruction (RAO) and clinically healthy horses, and to evaluate the effectiveness of potential therapeutic agents in reducing ROS and RNS in the tissues of these horses.

Objectives:We hypothesised that RAO‐affected horses would have high levels of reactive species and that the test agents would reduce them. The objectives were as follows: 1) to determine the level of ROS and RNS in pulmonary tissues (bronchial and arterial rings) of RAO‐affected and clinically healthy horses; and 2) to determine the ability of pentoxifylline, pyrrolidine‐dithiocarbamate and a combined use of endothelin A and B receptor antagonists (BQ123 and BQ788, respectively) in reducing reactive species.

Methods:Arterial and bronchial rings were collected from the diaphragmatic lung lobe of each horse immediately after euthanasia. The levels of ROS and RNS were measured in control tissues and those incubated with test agents, using an electron paramagnetic resonance instrument.

Results:The levels of ROS and RNS were significantly greater in arterial and bronchial tissues of RAO‐affected than of clinically healthy horses. Pentoxifylline and endothelin antagonists reduced both ROS and RNS in tissues from RAO‐affected horses. Basal levels of reactive species in clinically healthy horses were not affected by these agents. No difference in the level of reactive species was observed between arterial and bronchial tissues.

Conclusions:Horses affected by RAO had higher ROS and RNS than clinically healthy horses. Pentoxifylline and endothelin antagonists effectively reduced ROS and RNS in pulmonary tissues of RAO‐affected horses.

Potential relevance:The study suggested a potential use for pentoxifylline and endothelin antagonists in treating RAO‐affected horses. As endothelin is involved in physiological functions, therapeutic use of its antagonists is cautioned.
The use of equipment and training practices and the prevalence of owner‐reported ridden behaviour problems in UK leisure horses
Authors: HOCKENHULL J. , CREIGHTON E.
Published: April 2012

Reasons for performing study: UK leisure horses are owned primarily for riding. Ridden behaviour problems may compromise the use of the horse in this role and lead to harsh redress or relinquishment of the horse. Despite the consequences of these problems little is known about their prevalence or the working lives of UK leisure horses.

Objectives: To generate data on the work undertaken by leisure horses, the equipment and training practices used with them and prevalence of ridden behaviour problems.

Methods: An internet survey was used to generate horse‐level data from a convenience sample of leisure horse carers. Respondents were asked to report on their practices in the week prior to the survey's completion to minimise recall bias. The survey was online for one year to allow for seasonal variation in practices. Data were collected on the tack and equipment used on the horse, the regularity that professional services (e.g. farriers) were used, type of training employed and frequency the owner reported that horse displayed 15 ridden behaviour problems.

Results: The survey generated data on 1326 individual horses. Data describing practices relating to the horse's working life are presented. Ridden behaviour problems were reported in 91% of horses in the week preceding data collection.

Conclusions and potential relevance: Descriptive data on the working lives of UK leisure horses provides valuable baseline statistics for this largest section of the UK horse population. High prevalence of owner‐reported ridden behaviour problems represents a concern in such leisure horses and may indicate significant rider safety and horse welfare concerns.
Effect of viscous additives on the absorption and hepatic disposition of 5-fluorouracil (5-FU) after application to liver surface in rats
Authors: Kodama Yukinobu , Horishita Miyuki , Fumoto Shintaro , Mine Toyoharu , Miyamoto Hirotaka , Yoshikawa Naoki , Hirata Haruna , Sasaki Hitoshi , Nakamura Junzo , Nishida Koyo
Published: April 2012

Objectives

The aim was to study the effect of viscous additives on the absorption and hepatic disposition of 5-fluorouracil (5-FU) after application to the liver surface in rats.

Methods

5-FU solution with or without viscous additives was applied to the rat liver surface with a cylindrical diffusion cell. Then, blood and the remaining solution in the diffusion cell were collected at selected times, followed by excision of the liver. The excised liver was divided into three sites and assayed for 5-FU content.

Key findings

The absorption rate of 5-FU from the liver surface was decreased in the presence of carboxymethylcellulose sodium (CMC-Na) and polyvinyl alcohol (PVA) as compared with the control. The ka values of PVA 15% and CMC-Na 1% were reduced to about 80 and 67% of the control. The maximum plasma concentration of 5-FU was decreased by incorporation of viscous additives. The 5-FU concentration at the diffusion cell attachment site of the liver (site 1) plateaued at 180 min in the absence of viscous additives. On the other hand, the concentration of 5-FU at site 1 increased in a time-dependent manner until 360 min in the presence of viscous additives.

Conclusion

Viscous additives might be useful for retaining drugs at their application site and controlling the rate of absorption from the liver surface.
Computerized cognitive behavioural therapy and the therapeutic alliance: A qualitative enquiry
Authors: Barazzone Natalie , Cavanagh Kate , Richards David A
Published: April 2012

Objectives. Computerized cognitive behavioural therapy (cCBT) for depression has a growing evidence base, and is recommended as a treatment choice for depression in recent National Institute for Health and Clinical Excellence (NICE, 2009) guidelines to health services in England and Wales. cCBT programs are designed to translate the evidence‐based tasks and techniques of CBT into an accessible, multimedia format, but it is less clear whether they also translate critical common factors of therapy, which may be necessary for engagement and associated with therapeutic outcomes. This study investigates whether and to what extent three widely used cCBT programs for depression incorporate and convey key features that serve to establish, develop, and maintain a therapeutic alliance with program users.

Design. This study adopted a qualitative approach to develop a thematic framework of alliance features specific to cCBT.

Method. Three online cCBT programs designed to treat mild‐to‐moderate depression were investigated for alliance‐related themes and sub‐themes.

Results. The analysis revealed substantial evidence of therapeutic alliance features across the sample of cCBT programs, the prevalence and quality of which varied across relational stages.

Conclusions. cCBT programs build on traditional self‐help tools, offering unique relational features. Findings raise theoretical implications, in addition to guidance for future cCBT program development and service provision.
To master or perform? Exploring relations between achievement goals and conceptual change learning
Authors: Ranellucci John , Muis Krista R. , Duffy Melissa , Wang Xihui , Sampasivam Lavanya , Franco Gina M.
Published: April 2012

Background. Research is needed to explore conceptual change in relation to achievement goal orientations and depth of processing.

Aims. To address this need, we examined relations between achievement goals, use of deep versus shallow processing strategies, and conceptual change learning using a think‐aloud protocol.

Sample and Method. Seventy‐three undergraduate students were assessed on their prior knowledge and misconceptions about Newtonian mechanics, and then reported their achievement goals and participated in think‐aloud protocols while reading Newtonian physics texts.

Results. A mastery‐approach goal orientation positively predicted deep processing strategies, shallow processing strategies, and conceptual change. In contrast, a performance‐approach goal orientation did not predict either of the processing strategies, but negatively predicted conceptual change. A performance‐avoidance goal orientation negatively predicted deep processing strategies and conceptual change. Moreover, deep and shallow processing strategies positively predicted conceptual change as well as recall. Finally, both deep and shallow processing strategies mediated relations between mastery‐approach goals and conceptual change.

Conclusions. Results provide some support for Dole and Sinatra's (1998) Cognitive Reconstruction of Knowledge Model of conceptual change but also challenge specific facets with regard to the role of depth of processing in conceptual change.
Post‐event information presented in a question form eliminates the misinformation effect
Authors: Lee Yuh‐shiow , Chen Kuan‐Nan
Published: April 2012

This study investigated the influences of sentence surface forms on the misinformation effect. After viewing a film clip, participants received a post‐event narrative describing the events in the film. Critical sentences in the post‐event narrative, presented in either a statement or a question form, contained misinformation instead of questions with embedded false presuppositions; thus participants did not have to answer questions about the original event. During the final cued‐recall test, participants were informed that any relevant information presented in the post‐event narrative was not in the original event and that they should not report it. Consistent with previous findings, Experiment 1 demonstrated that post‐event information presented as an affirmative statement produced the misinformation effect. More importantly, post‐event information presented in a question form, regardless of whether it contained a misleading or studied item, increased the recall of correct information and reduced false recall. Experiment 2 replicated the main finding and ruled out an alternative explanation based on the salience of misleading items. Post‐event information presented in a question form created a condition similar to that which produces the testing effect.
The role of outcome inhibition in interference between outcomes: A contingency‐learning analogue of retrieval‐induced forgetting
Authors: Vadillo Miguel A. , Orgaz Cristina , Luque David , Cobos Pedro L. , López Francisco J. , Matute Helena
Published: April 2012

Current associative theories of contingency learning assume that inhibitory learning plays a part in the interference between outcomes. However, it is unclear whether this inhibitory learning results in the inhibition of the outcome representation or whether it simply counteracts previous excitatory learning so that the outcome representation is neither activated nor inhibited. Additionally, these models tend to conceptualize inhibition as a relatively transient and cue‐dependent state. However, research on retrieval‐induced forgetting suggests that the inhibition of representations is a real process that can be relatively independent of the retrieval cue used to access the inhibited information. Consistent with this alternative view, we found that interference between outcomes reduces the retrievability of the target outcome even when the outcome is associated with a novel (non‐inhibitory) cue. This result has important theoretical implications for associative models of interference and shows that the empirical facts and theories developed in studies of retrieval‐induced forgetting might be relevant in contingency learning and vice versa.
The linear transformation model with frailties for the analysis of item response times
Authors: Wang Chun , Chang Hua‐Hua , Douglas Jeffrey A.
Published: April 2012

The item response times (RTs) collected from computerized testing represent an underutilized source of information about items and examinees. In addition to knowing the examinees’ responses to each item, we can investigate the amount of time examinees spend on each item. In this paper, we propose a semi‐parametric model for RTs, the linear transformation model with a latent speed covariate, which combines the flexibility of non‐parametric modelling and the brevity as well as interpretability of parametric modelling. In this new model, the RTs, after some non‐parametric monotone transformation, become a linear model with latent speed as covariate plus an error term. The distribution of the error term implicitly defines the relationship between the RT and examinees’ latent speeds; whereas the non‐parametric transformation is able to describe various shapes of RT distributions. The linear transformation model represents a rich family of models that includes the Cox proportional hazards model, the Box–Cox normal model, and many other models as special cases. This new model is embedded in a hierarchical framework so that both RTs and responses are modelled simultaneously. A two‐stage estimation method is proposed. In the first stage, the Markov chain Monte Carlo method is employed to estimate the parametric part of the model. In the second stage, an estimating equation method with a recursive algorithm is adopted to estimate the non‐parametric transformation. Applicability of the new model is demonstrated with a simulation study and a real data application. Finally, methods to evaluate the model fit are suggested.
A genome resource to address mechanisms of developmental programming: determination of the fetal sheep heart transcriptome
Authors: Cox Laura A. , Glenn Jeremy P. , Spradling Kimberly D. , Nijland Mark J. , Garcia Roy , Nathanielsz Peter W. , Ford Stephen P.
Published: April 2012

Key points

The sheep is a valuable model for biomedical research, including the study of developmental programming mechanisms that are critical to better understand gene–environment interactions responsible for each individual's phenotype and predisposition to chronic diseases.

The lack of genetic and genomic resources for the sheep has limited the power of this model, impeding progress in emerging areas of pregnancy biology and other fields of biomedical research.

In this study, we examined the expressed fetal sheep heart transcriptome using high‐throughput sequencing technologies.

We identified 36,737 novel transcripts and describe genes, gene variants and pathways relevant to fundamental developmental mechanisms.

The data presented in this study provide a foundation of genetic information on the repertoire of genes expressed in the fetal heart transcriptome, which will augment annotation and assembly of the sheep genome.

Abstract  The pregnant sheep has provided seminal insights into reproduction related to animal and human development (ovarian function, fertility, implantation, fetal growth, parturition and lactation). Fetal sheep physiology has been extensively studied since 1950, contributing significantly to the basis for our understanding of many aspects of fetal development and behaviour that remain in use in clinical practice today. Understanding mechanisms requires the combination of systems approaches uniquely available in fetal sheep with the power of genomic studies. Absence of the full range of sheep genomic resources has limited the full realization of the power of this model, impeding progress in emerging areas of pregnancy biology such as developmental programming. We have examined the expressed fetal sheep heart transcriptome using high‐throughput sequencing technologies. In so doing we identified 36,737 novel transcripts and describe genes, gene variants and pathways relevant to fundamental developmental mechanisms. Genes with the highest expression levels and with novel exons in the fetal heart transcriptome are known to play central roles in muscle development. We show that high‐throughput sequencing methods can generate extensive transcriptome information in the absence of an assembled and annotated genome for that species. The gene sequence data obtained provide a unique genomic resource for sheep specific genetic technology development and, combined with the polymorphism data, augment annotation and assembly of the sheep genome. In addition, identification and pathway analysis of novel fetal sheep heart transcriptome splice variants is a first step towards revealing mechanisms of genetic variation and gene environment interactions during fetal heart development.
Hydrogen sulfide activates Ca2+ sparks to induce cerebral arteriole dilatation
Authors: Liang Guo Hua , Xi Qi , Leffler Charles W. , Jaggar Jonathan H.
Published: April 2012

Key points

Hydrogen sulfide (H2S), a gas produced by endothelial cells, relaxes smooth muscle cells within the vascular wall to increase organ blood flow and lower systemic blood pressure.

Mechanisms by which H2S produces vasodilatation in the cerebral circulation are unclear.

We demonstrate that H2S increases the quantity of calcium ions (Ca2+) contained with the sarcoplasmic reticulum (SR), the intracellular Ca2+ store, of cerebral arteriole smooth muscle cells.

This elevation in SR Ca2+ stimulates the generation of local intracellular Ca2+ signals called Ca2+ sparks, which in turn activate Ca2+‐sensitive potassium (KCa) channels on the cell membrane, leading to membrane hyperpolarization and vasodilatation.

Elucidating this novel mechanism of H2S‐induced vasodilatation is important to better understand physiological control of blood flow within the brain.
Topics in quantum physics with origins in astronomy: Two examples
Authors: Rau A. R. P.
Published: April 2012

Astronomy has provided the inspiration for several investigations in quantum physics. These topics can serve as pedagogical vehicles for undergraduate courses in physics and astronomy. Two examples are considered, atoms in strong magnetic fields and the negative ion of hydrogen. Both are fundamental problems of quantum physics which involve basic principles and techniques and are of practical interest and historically important. They also provide, in a form accessible to undergraduates, analogs of exotic topics such as the stability at a saddle of a potential surface, supersymmetry, dimensional reduction, and models for fundamental constants.
Cosmogenesis and the tipping pencil analogy
Authors: Adler Ronald J.
Published: April 2012

We present a toy model and scenario for cosmogenesis which provides an interesting rationale for the spatial flatness of the universe. The basic assumptions are that the cosmological scale factor obeys the standard Friedmann equation of general relativistic cosmology and that the equation is dominated by a cosmological constant term and a curvature term. The dynamics of the universe is then similar to that of a tipping pencil. The scale factor cannot remain at an unstable initial value of zero and must increase according to the uncertainty principle. If it is also assumed that the universe expands at the minimum asymptotic rate consistent with the uncertainty principle, the result is exact spatial flatness, rather than the near flatness obtained in standard inflation theory.
Teaching physics with Hubble’s law and dark matter
Authors: Wallace Colin S. , Prather Edward E.
Published: April 2012

Physics instructors can enrich, enliven, and enhance their courses with conceptually rich cosmology content. In this paper, we specifically discuss how instructors can integrate lessons on Hubble’s law (as it relates to the expansion of the universe and dark energy) and spiral galaxies’ rotation curves (as they relate to the presence of dark matter) into an introductory, college-level course on mechanics. These cosmology topics intersect with the content of introductory physics in a number of areas, such as students’ abilities to read and interpret graphs and their conceptual understandings of both kinematics and dynamics. Throughout this paper, we draw upon the results from, and research-validated curricula informed by, physics and astronomy education research. In particular, we feature the results from a national study we recently completed with introductory college-level general education astronomy students on the teaching and learning of cosmology.
Measurement of the Earth’s rotational speed via Doppler shift of solar absorption lines
Authors: Oostra Benjamin
Published: April 2012

This paper describes an experiment regularly presented to advanced undergraduate Physics students at the Universidad de los Andes in Bogotá, Colombia. The purpose of the experiment is to use high-resolution solar spectra to measure the horizontal speed of the laboratory caused by terrestrial rotation. Using this result, the radius of the Earth can be deduced. It is also possible to observe the Earth’s motion towards or away from the Sun, and hence compute our planet’s orbital eccentricity.
The first three rungs of the cosmological distance ladder
Authors: Krisciunas Kevin , DeBenedictis Erika , Steeger Jeremy , Bischoff-Kim Agnes , Tabak Gil , Pasricha Kanika
Published: April 2012

It is straightforward to determine the size of the Earth and the distance to the Moon without using a telescope. The methods have been known since the third century BCE. However, few astronomers have done this measurement from data they have taken. We use a gnomon to determine the latitude and longitude of South Bend, Indiana, and College Station, Texas, and determine the value of the radius of the Earth to be Rearth=6290 km, only 1.4% smaller than the known value. We use the method of Aristarchus and the size of the Earth’s shadow during the lunar eclipse of June 15, 2011 to estimate the distance to the Moon to be 62.3Rearth, 3.3% greater than the known mean value. We use measurements of the angular motion of the Moon against the background stars over the course of two nights, using a simple cross staff device, to estimate the Moon’s distance at perigee and apogee. We use simultaneous observations of asteroid 1996 HW1 obtained with small telescopes in Socorro, New Mexico, and Ojai, California, to obtain a value of the Astronomical Unit of (1.59±0.19)×108 km, about 6% too large. The data and methods presented here can easily become part of an introductory astronomy laboratory class.
Quantifying Crosstalk Among Interferon-γ, Interleukin-12, and Tumor Necrosis Factor Signaling Pathways Within a T
H
1 Cell Model
Authors: Klinke David J. , Cheng Ning , Chambers Emily
Published: April 2012

Combining experiments with mathematical modeling provides insights into the responses of T cells to cytokines.
Unmasking Functional Motifs Within Disordered Regions of Proteins
Authors: Das Rahul K. , Mao Albert H. , Pappu Rohit V.
Published: April 2012

The application of a computational approach to identify short linear motifs may enable the engineering of signaling networks.
Understanding Signaling Dynamics Through Synthesis
Authors: Slusarczyk Adrian L. , Weiss Ron
Published: April 2012

Signal propagation through a synthetic gene circuit containing a cell
contact–dependent positive feedback loop requires intracellular
amplification.
Focus Issue: Adding Math to the Signaling Toolkit
Authors: Wong Wei , Foley John F.
Published: April 2012

Computational approaches can reveal how cells interpret, process, and respond to signals.
To Cut or Not to Cut
Authors: Hurtley Stella M.
Published: April 2012

The membrane scission and cytokinesis ESCRT machinery may help to protect against genetic damage.
Open and Shut Case
Authors: Vinson Valda K.
Published: April 2012

Molecular dynamics simulations show how a voltage-gated channel closes.
Crosstalk Between Wnt and Insulin
Authors: Foley John F.
Published: April 2012

Both insulin and Wnt signaling in preadipocytes depend on the Wnt co-receptor LRP5.
Antimalarial Activity of the Anticancer Histone Deacetylase Inhibitor SB939
Authors: Sumanadasa Subathdrage D. M. , Goodman Christopher D. , Lucke Andrew J. , Skinner-Adams Tina , Sahama Ishani , Haque Ashraful , Do Tram Anh , McFadden Geoffrey I. , Fairlie David P. , Andrews Katherine T.
Published: April 2012

Histone deacetylase (HDAC) enzymes posttranslationally modify lysines on histone and nonhistone proteins and play crucial roles in epigenetic regulation and other important cellular processes. HDAC inhibitors (e.g., suberoylanilide hydroxamic acid [SAHA; also known as vorinostat]) are used clinically to treat some cancers and are under investigation for use against many other diseases. Development of new HDAC inhibitors for noncancer indications has the potential to be accelerated by piggybacking onto cancer studies, as several HDAC inhibitors have undergone or are undergoing clinical trials. One such compound, SB939, is a new orally active hydroxamate-based HDAC inhibitor with an improved pharmacokinetic profile compared to that of SAHA. In this study, the
in vitro
and
in vivo
antiplasmodial activities of SB939 were investigated. SB939 was found to be a potent inhibitor of the growth of
Plasmodium falciparum
asexual-stage parasites
in vitro
(50% inhibitory concentration [IC
50
], 100 to 200 nM), causing hyperacetylation of parasite histone and nonhistone proteins. In combination with the aspartic protease inhibitor lopinavir, SB939 displayed additive activity. SB939 also potently inhibited the
in vitro
growth of exoerythrocytic-stage
Plasmodium
parasites in liver cells (IC
50
, ∼150 nM), suggesting that inhibitor targeting to multiple malaria parasite life cycle stages may be possible. In an experimental
in vivo
murine model of cerebral malaria, orally administered SB939 significantly inhibited
P. berghei
ANKA parasite growth, preventing development of cerebral malaria-like symptoms. These results identify SB939 as a potent new antimalarial HDAC inhibitor and underscore the potential of investigating next-generation anticancer HDAC inhibitors as prospective new drug leads for treatment of malaria.
In Vitro
Anti-Trypanosoma cruzi Activity of Dronedarone, a Novel Amiodarone Derivative with an Improved Safety Profile
Authors: Benaim Gustavo , Hernandez-Rodriguez Vanessa , Mujica-Gonzalez Sheira , Plaza-Rojas Lourdes , Silva May Li , Parra-Gimenez Nereida , Garcia-Marchan Yael , Paniz-Mondolfi Alberto , Uzcanga Graciela
Published: April 2012

Amiodarone, a commonly used antiarrhythmic, is also a potent and selective anti-
Trypanosoma cruzi
agent. Dronedarone is an amiodarone derivative in which the 2,5-diiodophenyl moiety of the parental drug has been replaced with an unsubstituted phenyl group aiming to eliminate the thyroid toxicity frequently observed with amiodarone treatment. Dronedarone has been approved by the Food and Drug Administration (FDA), and its use as a safe antiarrhythmic has been extensively documented. We show here that dronedarone also has potent anti-
T. cruzi
activity, against both extracellular epimastigotes and intracellular amastigotes, the clinically relevant form of the parasite. The 50% inhibitory concentrations against both proliferative stages are lower than those previously reported for amiodarone. The mechanism of action of dronedarone resembles that of amiodarone, as it induces a large increase in the intracellular Ca
2+
concentration of the parasite, which results from the release of this ion from intracellular storage sites, including a direct effect of the drug on the mitochondrial electrochemical potential, and through alkalinization of the acidocalcisomes. Our results suggest a possible future repurposed use of dronedarone for the treatment of Chagas' disease.
Antiviral Effects of Small Interfering RNA Simultaneously Inducing RNA Interference and Type 1 Interferon in Coxsackievirus Myocarditis
Authors: Ahn Jeonghyun , Ko Ara , Jun Eun Jung , Won Minah , Kim Yoo Kyum , Ju Eun-Seon , Jeon Eun Seok , Lee Heuiran
Published: April 2012

Antiviral therapeutics are currently unavailable for treatment of coxsackievirus B3, which can cause life-threatening myocarditis. A modified small interfering RNA (siRNA) containing 5′-triphosphate, 3p-siRNA, was shown to induce RNA interference and interferon activation. We aimed to develop a potent antiviral treatment using CVB3-specific 3p-siRNA and to understand its underlying mechanisms. Virus-specific 3p-siRNA was superior to both conventional virus-specific siRNA with an empty hydroxyl group at the 5′ end (OH-siRNA) and nonspecific 3p-siRNA in decreasing viral replication and subsequent cytotoxicity. A single administration of 3p-siRNA dramatically attenuated virus-associated pathological symptoms in mice with no signs of toxicity, and their body weights eventually reached the normal range. Myocardial inflammation and fibrosis were rare, and virus production was greatly reduced. A nonspecific 3p-siRNA showed relatively less protective effect under identical conditions, and a virus-specific OH-siRNA showed no protective effects. We confirmed that virus-specific 3p-siRNA simultaneously activated target-specific gene silencing and type I interferon signaling. We provide a clear proof of concept that coxsackievirus B3-specific 3p-siRNA has 2 distinct modes of action, which significantly enhance antiviral activities with minimal organ damage. This is the first direct demonstration of improved antiviral effects with an immunostimulatory virus-specific siRNA in coxsackievirus myocarditis, and this method could be applied to many virus-related diseases.
pfmdr1
Amplification Is Related to Increased Plasmodium falciparum In Vitro Sensitivity to the Bisquinoline Piperaquine
Authors: Veiga M. I. , Ferreira P. E. , Malmberg M. , Jörnhagen L. , Björkman A. , Nosten F. , Gil J. P.
Published: April 2012

The 4-aminoquinoline bisquinoline piperaquine is an important partner drug in one of the presently recommended artemisinin combination therapies. Recent clinical trials have confirmed its high efficacy in combination with dihydroartemisinin. Resistance to piperaquine alone has, however, been documented. Amplification in copy number of the
Plasmodium falciparum
multidrug resistance locus on chromosome 5, containing the
pfmdr1
gene, has been shown to confer resistance to structurally unrelated antimalarials. Through the determination of the 50% inhibitory concentrations (IC
50
s) and IC
90
s for piperaquine and chloroquine in a set of 46 adapted
P. falciparum
cultures originating from the Thai-Burmese border, we have characterized the regions around the
pfmdr1
gene and identified a significant association between the presence of
pfmdr1
duplications and enhanced sensitivity to piperaquine (
P
= 0.005 for IC
50
and
P
= 0.002 for IC
90
) and chloroquine, reaching statistical significance at IC
90
s (
P
= 0.026). These results substantiate the potential importance of
pfmdr1
copy number amplifications in the efficacy of the combination therapy piperaquine-dihydroartemisinin. It supports the rational use of 4-aminoquinolines and artemisinin-based compounds, as they independently select for mutually incompatible combinations of mutations.