bluuebunny/crossref_metadata_2025 huggingface dataset:
The other side of innovation
Authors: Pitts Peter J.
Published: January 2013

Government sponsored comparative effectiveness research is the first step towards allowing Uncle Sam to push a restrictive formulary on more and more Americans â€“ with step one in the process being unfettered (and unregulated) communications efforts. Unless we are aware and vigilant, such cost-think may very well lead to a single-payer system referred to in cost-think as â€œuniversal coverageâ€ â€“ but in reality will be nothing short of healthcare rationing. There are many dangerous implications, but the most frightening is the chilling effect so-called comparative effectiveness programs will have on the future of healthcare innovation.
Fixing a broken drug development process
Authors: Holland John
Published: January 2013

It costs about $1.2 billion to bring a single new drug to market in the U.S. today.[1] With a combination of high late-stage failure rates and the high cost of drug trials, the number of new drugs being approved by the FDA has flat-lined at historically low levels, falling from 53 in 1996 to just 19 in 2009.[2] If the cost of drug trials doesnâ€™t come down, we will see far fewer new drugs on pharmacy shelves. [1] Pharmaceutical Research and Manufacturers of America Profile 2009. Washington, DC: PhRMA. [2] Hughes B. 2009 Drug Approvals. Nature Reviews Drug Discovery 9, 89-92 (February 2010)
Use of medicines for carved out indications - Time for a change in approach?
Authors: Cordery Brian
Published: January 2013

All stake-holders in the pharmaceutical industry recognise that valuable new medicines can be obtained from investing in the research and development of new uses for existing drugs.Â  The present system of awarding second medical use patents to originators which develop new and inventive medicines from known drugs does not provide sufficient incentive to this part of the industry.Â  Moreover the status of second medical use patents is so uncertain that generics do not know where they stand.Â  A solution which provides proper protection to second medical use patents is required to bring certainty and fairness to all involved in the industry to the ultimate benefit of patients.
Positioning Oneself in Mathematics Education Research
Authors: D'Ambrosio Beatriz , Frankenstein Marilyn , Gutiérrez Rochelle , Kastberg Signe , Martin Danny Bernard , Moschkovich Judit , Taylor Edd , Barnes David
Published: January 2013

This dialogue, also extracted from a conversation among members of the Equity Special Issue Editorial Panel, involves the role of a researcher's position in mathematics education. It raises issues about the non-neutrality of research; the relationship between a researcher's identity and the design, analysis, and conclusions of a research study; the benefits for researchers and participants in positioning oneself; and the role of mathematics education in this endeavor.
Addressing Racism
Authors: D'Ambrosio Beatriz , Frankenstein Marilyn , Gutiérrez Rochelle , Kastberg Signe , Martin Danny Bernard , Moschkovich Judit , Taylor Edd , Barnes David
Published: January 2013

This is a dialogue extracted from a conversation among some members of the Equity Special Issue Editorial Panel (Beatriz D'Ambrosio; Marilyn Frankenstein; Rochelle Gutiérrez, Special Issue editor; Signe Kastberg; Danny Martin; Judit Moschkovich; Edd Taylor; and David Barnes) about racism in mathematics education. It raises issues about the use of terms such as race and racism; understanding fields of research outside of mathematics education; the kinds of racialization processes that occur for students, teachers, and researchers; the social context of students; the achievement gap; and the role of mathematics education in the production of race.
Negotiating the “White Male Math Myth”: African American Male Students and Success in School Mathematics
Authors: Stinson David W.
Published: January 2013

This article shows how equity research in mathematics education can be decentered by reporting the “voices” of mathematically successful African American male students as they recount their experiences with school mathematics, illustrating, in essence, how they negotiated the White male math myth. Using post-structural theory, the concepts discourse, person/identity, and power/agency are reinscribed or redefined. The article also shows that using a post-structural reinscription of these concepts, a more complex analysis of the multiplicitous and fragmented robust mathematics identities of African American male students is possible—an analysis that refutes simple explanations of effort. The article concludes, not with “answers,” but with questions to facilitate dialogue among those who are interested in the mathematics achievement and persistence of African American male students—and equity and justice in the mathematics classroom for all students.
One Size Does NOT Fit All: Achieving Equity in Māori Mathematics Classrooms
Authors: Meaney Tamsin , Trinick Tony , Fairhall Uenuku
Published: January 2013

In this article, we explore how a school in Aotearoa [New Zealand] infuses the identity of Indigenous students into the school-based curriculum through the promotion of their language and culture in mathematics lessons. Bernstein's pedagogic device illustrates how teachers' practices were influenced by being able to think the “unthinkable.” This came from the contestation that arose when competing bodies of knowledge had to be integrated both at the school level and at the classroom level. For equity to be achieved regarding students' mathematics learning, parents' and the community's aspirations for students' education need to be infused into debates about the knowledge that teachers are expected to include in their teaching. This enables the local context to make a positive contribution to students' learning. It also implies that programs for improvement should not be imposed on schools unless there are opportunities for them to be adapted to the needs of individual schools.
Power, Identity, and Mathematical Practices Outside and Inside School
Authors: Nasir Na'ilah Suad , de Royston Maxine McKinney
Published: January 2013

This article explores how issues of power and identity play out in mathematical practices and offers a perspective on how we might better understand the sociopolitical nature of teaching and learning mathematics. We present data from studies of mathematics teaching and learning in out-of-school settings, offering a sociocultural, then a sociopolitical analysis (attending to race, identity, and power), noting the value of the latter. In doing so, we develop a set of theoretical tools that move us from the sociocultural to the sociopolitical in studies of mathematics teaching and learning.
Effects of Nutraceuticals and Botanicals on Macrophage Cholesterol Efflux: Implications for Atherosclerosis
Authors: Sotherden Grace Megumi , Uto-Kondo Harumi , Ayaori Makoto , Ikewaki Katsunori
Published: January 2013

To date, the literature on high-density lipoprotein (HDL) levels as an inverse risk factor for atherosclerosis has mainly been observational, and it is likely that the metabolism and function of HDL is a more significant determinant of cardiovascular disease. As an example, as cholesterol is effluxed out of macrophages and carried to the liver via HDL for excretion, reduced cholesterol efflux can result in increased cholesterol accumulation. In terms of atherosclerosis risk, increasing cholesterol efflux is theoretically a strategy that can be considered as the groundwork of cardiovascular disease treatment and prevention. However, until now, there has not been a pharmaceutical agent that has effectively increased reverse cholesterol transport (RCT) at all steps of the process. Here is a review of the research on natural compounds present in edible foods and their observed in vitro and in vivo (and even ex vivo) effects on the first step of RCT: macrophage cholesterol efflux. The findings here are preliminary and contradictory, making it hard to translate the evidence on most of these naturally occurring agents into clinical applications.
Influence of Xpand Nitric Oxide Reactor, L-Arginine Alpha-Ketoglutarate, and Caffeine Supplementation on Calf Muscle Re-Oxygenation During and after Acute Resistance Exercise
Authors: Collins Brittany C. , Sapp Ryan , LaManca John , Wolff Christopher , Miranda Edwin , Gutierrez Vincent , Mazzetti Scott A.
Published: January 2013

Xpand Nitric Oxide Reactor is a ‘cocktail’ supplement proposed to improve skeletal muscle blood flow via arginine’s effect on nitric oxide synthesis and vasodilation. Two other major ingredients, caffeine and creatine, cause vasoconstriction, which could potentially counteract the proposed hemodynamic effects of arginine. The purpose of this study was to examine the influence of Xpand Nitric Oxide Reactor on muscle re-oxygenation after resistance exercise compared to supplementation with constituent ingredients L-arginine alpha-ketoglutarate and caffeine. Nine recreationally active men (21±1y) performed 3 sets of 20 repetitions of seated single-leg calf raise at 60% 1-RM with 3 min rests. The same calf raise exercise was performed following 4 separate supplementation conditions: L-arginine alpha-ketoglutarate (AAKG), caffeine (CAFF), Xpand Nitric Oxide Reactor (XPAND), and placebo (PLAC). Soleus muscle re-oxygenation time was measured before, during, and immediately after exercise using near infrared spectroscopy. Supplementation with XPAND (0.43±0.03), AAKG (0.34±0.02), and CAFF (0.45±0.05) did not significantly affect muscle re-oxygenation halftime (minutes) compared to placebo (0.35±0.04). An arginine containing ‘cocktail’ supplement did not affect skeletal muscle re-oxygenation after resistance exercise, possibly due to a wash-out effect caused by the multiple ingredients.
Stability of Three Different Galenic Liquid Formulations Compounded from Tablet Containing Glibenclamide
Authors: Di Folco Ugo , Falco Daniela De , Marcucci Fabio , Nobili Graziella , Moretti Vincenzo , Gioventù Giorgio , Tubili Claudio
Published: January 2013

The suspensions of sulfonylurea glyburide (glibenclamide) are compounded extemporaneously for patients suffering from transitional and Permanent Neonatal Diabetes mellitus (PND). The purpose of this study is to compare the stability of three different galenic liquid formulations compounded from tablet containing glibenclamide. The samples were stored at refrigerated (2-8°C) and room temperature and analyzed at different times. All formulations analysed are stable for at least 90 days, but only two guarantee the administration responding to prescription, especially when it comes to giving dosages very small.
State Collapse and Household Resilience in the Oaxaca Valley of Mexico
Authors: Faulseit Ronald K.
Published: January 2013

A two-year project of survey, surface collection, and excavation on the hill of Cerro Danush within the site of Dainzú-Macuilxóchitl in Oaxaca, Mexico, was focused on identifying and characterizing the Late Classic (A.D. 600–850/900) and Early Postclassic (A.D. 850/900–1300) components of the site, which coincide with the political fragmentation and reorganization of complex society within the Valley of Oaxaca. The transition in sociopolitical organization from the Classic to Postclassic has been the subject of several research projects, but few, if any, have clearly identified an Early Postclassic settlement. A radiocarbon analysis of charcoal samples collected during the excavation of a residential complex on Cerro Danush reveals its most recent period of occupation to be between A.D. 1000 and 1300, placing it firmly within the Early Postclassic. The excavation data are contextualized with data from the surface collection, illuminating patterns of Late Classic political fragmentation and Early Postclassic household resilience. Since Dainzú-Macuilxóchitl emerged in the Late Postclassic (A.D. 1300–1521) as a powerful city-state, exploring its Early Postclassic component contributes to the study of how societies reorganize on a local level after the collapse of centralized authority, such as the Classic period Monte Albán state.
La Ocupacion Humana Durante La Transicion Pleistoceno-Holoceno (11,000–9000 a.P.) En Las Sierras Centrales De Argentina
Authors: Rivero Diego E.
Published: January 2013

El objetivo de este trabajo consiste en el análisis de la evidencia arqueológica de las Sierras Centrales de Argentina correspondiente al período que abarca desde la Transición Pleistoceno-Holoceno (11,000 – 9000 a.P.) hasta fines del Holoceno Temprano (ca. 6000 a.P.) y sus implicancias para el conocimiento del proceso de poblamiento inicial de este sector de Argentina. Proponemos la existencia de una presencia humana poco intensa y discontinua durante la Transición Pleistoceno-Holoceno y que la intensidad de la ocupación aumenta notablemente con posterioridad a ca. 8000 a.P. Las evidencias sugieren que desde la llegada de los primeros grupos a las Sierras Centrales ca. 11,000 a.P. hasta el logro de la colonización efectiva del área (sensu Borrero 1989-1990) ocurrida a partir de ca. 8000 a.P., se produjo un proceso de exploración caracterizado por muy bajas densidades poblacionales que bien pudo incluir colonizaciones fallidas. Estas conclusiones alertan sobre el empleo de modelos de poblamiento que asuman continuidad biológica-cultural durante todo el Holoceno.
A Clinical Objective IMRT QA Method Based on Portal Dosimetry and Electronic Portal Imager Device (EPID) Measurement
Authors: Zhang Miao , Qin Songbing , Chen Ting , Kim Sung , Jabbour Salma , Haffty Bruce , Yue Ning J.
Published: January 2013

Clinical objective IMRT QA is a new approach to conduct patient specific IMRT QA by evaluating the QA result based on metrics like the structure dose volume histograms (DVH) on the planning CT image. Different from traditional 2D planar dose based IMRT QA in which all the measurements and evaluations were based on a phantom, clinical objective IMRT QA reveals the direct clinical impact of any measured variation based on the predicted delivered dose to the patient target volumes and critical organs. In this study, we proposed a method to implement the clinical objective IMRT QA procedure by using generally available dosimetry equipment in a radiation oncology clinic. The proposed procedure was tested and validated on five IMRT plans by using a solid water phantom, which served as a test patient, along with total 30 ion chamber measurements. The result showed that the proposed QA procedure successfully achieved the goal of clinical objective IMRT QA. Based on the ion chamber measurements, the QA procedure predicted that the average variations between the planned and the delivered doses were within 1.9%. This method may hold potentials to help radiation oncology clinics to move from the traditional IMRT QA to the clinical objective IMRT QA.
EZH2 Regulates the Expression of p16 in the Nasopharyngeal Cancer Cells
Authors: Zhong Jing , Min Lishan , Huang Huilian , Li Liqin , Li Dongli , Li Jing , Ma Zhihong , Dai Licheng
Published: January 2013

The increasing evidence supported the role of Enhancer of Zeste Homolog 2 (EZH2) in the cancer development and progression. However, its precise role in the tumorigenesis of Nasopharyngeal Carcinoma (NPC) remains to be elucidated. EZH2 was depleted by retroviral infection in the NPC cells (HK-1, CNE-2, CNE-1 and C666-1). The degree of EZH2 knockdown was then assessed by real-time quantitative PCR and Western Blot analysis. Cell proliferation was assessed using the soluble tetrazolium salt (MTS) cell proliferation assay, and cell cycle was measured by FACS test. The methylation status of p16INK4a was determined by bisulphate treatment of the DNA, followed by MSP. EZH2 was over-expressed in NPC cells, and the expression in undifferentiated-derived NPC cells (CNE-1, C666-1) was more significant than differentiated-derived NPC cells (HK-1, CNE-2). EZH2 was successfully depleted after retroviral infection in C666-1 cells, and the EZH2 depletion could inhibit the proliferation and arrested G1/S phase of NPC cells. In addition, both mRNA and protein levels of p16INK4a increased significantly in presence of EZH2 depletion. The further Methylation-Specific Polymerase Chain Reaction (MSP) assay suggested that over-expressed EZH2 may contribute to the reduction of p16INK4a expression by hyper methylating its promoter. EZH2 is overexpressed in NPC and reduces expression of p16INK4a by influencing methylation, opening therapeutic options.
Outcomes of a mentored research competition for authoring pediatric case reports in chiropractic
Authors: Pohlman Katherine A. , Vallone Sharon , Nightingale Lia M.
Published: January 2013

Objective

A chiropractic pediatric specialist often encounters novel clinical findings not reported currently in the literature. This project matched board certified chiropractic pediatric specialists with a mentor experienced in scientific writing to co-author a research paper to add to the literature base available on chiropractic pediatric practice.

Methods

Clinicians who had received their Diplomate in Clinical Chiropractic Pediatrics and mentors in scientific writing were teamed up. Two surveys were conducted to collect quantitative data, and focus groups were held to gather qualitative data about the overall experience of the mentor and mentee (clinicians) participating in the study. The first survey was sent to the clinicians to gather information about their research idea and their experience in research. The second survey was conducted upon project completion by clinicians and mentors. A project wiki was used as a communication strategy.

Results

Ten reports were submitted by authorship teams. Time spent on this project was an average of 58 hours by clinicians and 36 hours by the mentors. Mentors aided by adding content material, editing manuscripts, and educating the clinicians in the art of writing a paper. Improvements for this project included clearer mentoring guidelines and not using the wiki as a communication venue.

Conclusion

The project ultimately fulfilled the goal of using a mentorship model to facilitate scientific writing education and ease the anxiety of authoring a first publication. The overall experience was “good”; however, there are opportunities for improvement.
SHAPE–Seq: High‐Throughput RNA Structure Analysis
Authors: Mortimer Stefanie A. , Trapnell Cole , Aviran Sharon , Pachter Lior , Lucks Julius B.
Published: December 2012

Knowledge of RNA structure is critical to understanding both the important functional roles of RNA in biology and the engineering of RNA to control biological systems. This article contains a protocol for selective 2′‐hydroxyl acylation analyzed by primer extension and sequencing (SHAPE‐Seq) that, through a combination of structure‐dependent chemical probing and next‐generation sequencing technologies, achieves structural characterization of hundreds of RNAs in a single experiment. This protocol is applicable in a variety of conditions, and represents an important tool for understanding RNA biology. The protocol includes methods for the design and synthesis of RNA mixtures for study, and the construction and analysis of structure‐dependent sequencing libraries that reveal structural information of the RNAs in the mixtures. The methods are generally applicable to studying RNA structure and interactions in vitro in a variety of conditions, and allows for the rapid characterization of RNA structures in a high‐throughput manner. Curr. Protoc. Chem. Biol. 4:275‐297 © 2012 by John Wiley & Sons, Inc.
Specificity Profiling of Protein‐Binding Domains Using One‐Bead‐One‐Compound Peptide Libraries
Authors: Kunys Andrew R. , Lian Wenlong , Pei Dehua
Published: December 2012

One‐bead‐one‐compound (OBOC) libraries consist of structurally related compounds (e.g., peptides) covalently attached to a solid support, with each resin bead carrying a unique compound. OBOC libraries of high structural diversity can be rapidly synthesized and screened without the need for any special equipment, and therefore can be employed in any chemical or biochemical laboratory. OBOC peptide libraries have been widely used to map the ligand specificity of proteins, to determine the substrate specificity of enzymes, and to develop inhibitors against macromolecular targets. They have proven particularly useful in profiling the binding specificity of protein modular domains (e.g., SH2 domains, BIR domains, and PDZ domains); subsequently, the specificity information can be used to predict the protein targets of these domains. The protocols outlined in this article describe the methodologies for synthesizing and screening OBOC peptide libraries against SH2 and PDZ domains, and the related data analysis. Curr. Protoc. Chem. Biol. 4:331‐355 © 2012 by John Wiley & Sons, Inc.
A Screening Protocol for Identification of Functional Mutants of RNA Editing Adenosine Deaminases
Authors: Eifler Tristan , Chan Dalen , Beal Peter A.
Published: December 2012

Genetic screens can be used to evaluate a spectrum of mutations and thereby infer the function of particular residues within a protein. The Adenosine Deaminase Acting on RNA (ADAR) family of RNA‐editing enzymes selectively deaminate adenosines (A) in double‐helical RNA, generating inosine (I). The protocol described here exploits the editing activity of ADAR2 in a yeast‐based screen by inserting an editing substrate sequence with a stop codon incorporated at the editing site upstream from the sequence encoding the reporter α‐galactosidase. A‐to‐I editing changes the stop codon to a tryptophan codon, allowing normal expression of the reporter. This technique is particularly well‐suited for screening ADAR and ADAR substrate mutant libraries for editing activity. Curr. Protoc. Chem. Biol. 4:357‐369 © 2012 by John Wiley & Sons, Inc.
Evaluation of the suchey–brooks method of age estimation in an Australian subpopulation using computed tomography of the pubic symphyseal surface
Authors: Lottering Nicolene , MacGregor Donna M. , Meredith Matthew , Alston Clair L. , Gregory Laura S.
Published: January 2013

Despite the prominent use of the Suchey–Brooks (S–B) method of age estimation in forensic anthropological practice, it is subject to intrinsic limitations, with reports of differential interpopulation error rates between geographical locations. This study assessed the accuracy of the S–B method to a contemporary adult population in Queensland, Australia and provides robust age parameters calibrated for our population. Three‐dimensional surface reconstructions were generated from computed tomography scans of the pubic symphysis of male and female Caucasian individuals aged 15–70 years (n = 195) in Amira® and Rapidform®. Error was analyzed on the basis of bias, inaccuracy and percentage correct classification for left and right symphyseal surfaces. Application of transition analysis and Chi‐square statistics demonstrated 63.9 and 69.7% correct age classification associated with the left symphyseal surface of Australian males and females, respectively, using the S–B method. Using Bayesian statistics, probability density distributions for each S–B phase were calculated, providing refined age parameters for our population. Mean inaccuracies of 6.77 (±2.76) and 8.28 (±4.41) years were reported for the left surfaces of males and females, respectively; with positive biases for younger individuals (<55 years) and negative biases in older individuals. Significant sexual dimorphism in the application of the S–B method was observed; and asymmetry in phase classification of the pubic symphysis was a frequent phenomenon. These results recommend that the S–B method should be applied with caution in medico‐legal death investigations of Queensland skeletal remains and warrant further investigation of reliable age estimation techniques. Am J Phys Anthropol, 2013. © 2013 Wiley Periodicals, Inc.
Chylous ascites after hepatopancreatobiliary surgery
Authors: Kuboki S , Shimizu H , Yoshidome H , Ohtsuka M , Kato A , Yoshitomi H , Furukawa K , Miyazaki M
Published: January 2013

Background

Postoperative chylous ascites following abdominal surgery is uncommon. It potentially induces malnutrition and immunodeficiency, contributing to increased mortality. In the field of hepatopancreatobiliary (HPB) surgery, no large studies have been conducted that focused on postoperative chylous ascites. The aim of this study was to determine the incidence, risk factors and management of chylous ascites following HPB surgery, with particular emphasis on pancreatic resection.

Methods

Consecutive patients who had HPB surgery between 2000 and 2011 at a single institution were reviewed retrospectively. Chyle leak was defined as 100 ml/day or more of milky, amylase-free peritoneal fluid with a triglyceride concentration of 110 mg/dl or above. Risk factors for chylous ascites associated with pancreatic resection and the clinical efficacy of octreotide in treating chylous ascites were evaluated.

Results

Of 2002 consecutive patients who underwent HPB surgery during the study period, 21 (1·0 per cent) developed chylous ascites. Chylous ascites occurred relatively frequently in patients who had a pancreatic resection, such as pancreaticoduodenectomy (3·3 per cent) or distal pancreatectomy (3·8 per cent). Multivariable analysis revealed that manipulation of the para-aortic area (P < 0·001), retroperitoneal invasion (P = 0·031) and early enteral feeding after operation (P < 0·001) were independent risk factors for chylous ascites following pancreatic resection. Octreotide treatment decreased drainage output of chylous ascites on day 1 after initiation of treatment (P = 0·002).

Conclusion

Chylous ascites is a rare complication following HPB surgery. It is more common after pancreatic resection. Treatment with octreotide combined with total parenteral nutrition is recommended.
The Return‐Implied Volatility Relation for Commodity ETFs
Authors: Padungsaksawasdi Chaiyuth , Daigler Robert T.
Published: January 2013

We examine the return‐implied volatility relation by employing “commodity” option VIXs for the euro, gold, and oil. This relation is substantially weaker than for stock indexes. We propose several potential reasons for these unusually weak results. Also, gold possesses an unusual positive contemporaneous return coefficient, which is consistent with a demand volatility skew rather than the typical investment skew. Moreover, the euro and gold are not asymmetric. We relate the results to trading strategies, algorithmic trading, and behavioral theories. An important conclusion of the study is that important differences exist regarding implied volatility for certain types of assets that have not yet been explained in the literature; namely, the results in this study concerning commodity ETFs versus stock indexes, plus previous research on stock indexes versus individual stocks, and the pricing of stock index options versus individual stock options. © 2013 Wiley Periodicals, Inc. Jrl Fut Mark 34:261–281, 2014
Simulation‐based estimates of safety distances for pipeline transportation of carbon dioxide
Authors: Mazzoldi Alberto , Picard David , Sriram Papagudi G. , Oldenburg Curtis M.
Published: January 2013

Pipeline transportation of fluids is a proven technology for moving large quantities of liquids and gases (e.g. hydrocarbons, hazardous liquids, hydrogen). The anticipated introduction of large‐scale geologic carbon sequestration (GCS) as a means of reducing greenhouse gas (GHG) emissions will require the ability to transport massive amounts of carbon dioxide (CO2) safely and economically. To accommodate GCS demands, the existing US and European CO2 pipeline infrastructure may eventually have to be expanded to be comparable in size to natural gas and oil pipeline systems. Furthermore, the new pipeline infrastructure will inevitably intersect with population centers as it connects sources with sink areas. There are important unanswered questions about pipeline network requirements, regulations, utility cost recovery, economics, regulatory classification of CO2 itself, and pipeline safety. The focus of this research is on this last aspect, i.e. safety of the general public, workers, and property related to the transportation of CO2. We carried out simulations that coupled two computational fluid dynamics (CFD) codes to determine: (i) leakage rates from fully ruptured above‐ground CO2 pipelines for a typical pipeline fluid composition, and (ii) the resulting atmospheric dispersion of the gas near the broken pipe. Using threshold values for atmospheric CO2 concentration, our work shows that concentrations dangerous to human health can extend on the order of hundreds of meters from the ruptured pipeline. This work contributes to the knowledge base needed to establish safety distances for routing CO2 pipelines through inhabited and other sensitive areas. © 2012 Society of Chemical Industry and John Wiley & Sons, Ltd
FEW: A workflow tool for free energy calculations of ligand binding
Authors: Homeyer Nadine , Gohlke Holger
Published: January 2013

In the later stages of drug design projects, accurately predicting relative binding affinities of chemically similar compounds to a biomolecular target is of utmost importance for making decisions based on the ranking of such compounds. So far, the extensive application of binding free energy approaches has been hampered by the complex and time‐consuming setup of such calculations. We introduce the free energy workflow (FEW) tool that facilitates setup and execution of binding free energy calculations with the AMBER suite for multiple ligands. FEW allows performing free energy calculations according to the implicit solvent molecular mechanics (MM‐PB(GB)SA), the linear interaction energy, and the thermodynamic integration approaches. We describe the tool's architecture and functionality and demonstrate in a show case study on Factor Xa inhibitors that the time needed for the preparation and analysis of free energy calculations is considerably reduced with FEW compared to a fully manual procedure. © 2013 Wiley Periodicals, Inc.
Multi‐proxy study of Holocene environmental change and human activity in the Central Apennine Mountains, Italy
Authors: Brown A. G. , Hatton J. , Selby K. A. , Leng M. J. , Christie N.
Published: January 2013

This paper describes a multi‐proxy palaeoecological investigation undertaken in conjunction with an archaeological survey of the Upper Sangro Valley in the Abruzzo National Park, Central Italy. Despite being a biodiversity hotspot and regarded as a near‐pristine area, the pollen, spore and diatom data all show major changes in the vegetation extending to over 2000 m a.s.l. during the mid to late Holocene. Although there are changes in ecological composition earlier in the Holocene they are different in type and magnitude from the changes which began about 800 cal a BC. The pollen and diatom evidence do not correlate well with regional palaeoclimate data, or on‐site isotopic evidence, but do appear to be related to Samnite (later Iron Age) clearance and upland grazing associated with transhumance and later annexation (and centuriation) of the lower slopes by Roman surveyors. The greatest change in vegetation was during the period c. AD 500–600 and corresponds with the Byzantine–Gothic Wars, and Lombard–Carolingian settlement reorganization into nucleated hilltop settlements which managed upland grazing. This pattern of intensive land use at all altitudes persisted until the early 20th century and only changed following rural depopulation after World War II. These data illustrate how cultural factors had a profound effect on this mountainous region which, in this case, far outweighed the effects of climatic fluctuations which are known to have occurred from both this study area and the region. Copyright © 2012 John Wiley & Sons, Ltd.
Barcode DNA high‐resolution melting (Bar‐HRM) analysis as a novel close‐tubed and accurate tool for olive oil forensic use
Authors: Ganopoulos Ioannis , Bazakos Christos , Madesis Panagiotis , Kalaitzis Panagiotis , Tsaftaris Athanasios
Published: January 2013

BACKGROUND

The adulteration of high‐priced olive oil with low‐cost oils and the fraudulent labelling of oil products make the identification and traceability of vegetable oil species in the food chain very important. This paper describes a high‐resolution melting analysis‐based method using chloroplast barcoding regions as target (Bar‐HRM) to obtain barcoding information for the major vegetable oil species and to quantitatively identify the botanical origin of plant oils. The detection of adulteration of olive oil with canola oil was used as a case study.

RESULTS

The proposed method was capable of distinguishing among different vegetable oil species and detecting a level of 1% (w/w) of canola oil in olive oil.

CONCLUSION

Bar‐HRM analysis is a more accurate, faster and less costly alternative method to authenticate vegetable oils, including olive oil, and to detect mixtures of oils. © 2013 Society of Chemical Industry
Associations of body fat percent and body mass index with childhood asthma by age and gender
Authors: Yiallouros Panayiotis K. , Lamnisos Demetris , Kolokotroni Ourania , Moustaki Maria , Middleton Nicos
Published: January 2013

Objective

High body mass index (BMI) has been shown to be associated with asthma, but the pattern of this association is still unclear and may differ by gender or stage of puberty. BMI is only a proxy of adiposity, whereas estimation of body fat percent (BF%) by the bioimpedance technique is considered an accurate measure of adiposity. We investigated whether BMI and BF% behave differently in their association with asthma between genders, before and during adolescence.

Design and Methods

In this cross‐sectional study of 10,981 schoolchildren, we used logistic regression models to examine the pattern of association of BMI and BF% with asthma.

Results

In the case of BF%, both the highest (odds ratio [OR]: 1.68, 95% confidence interval [95% CI]: 1.21‐2.30) and lowest (OR: 1.59, 95% CI: 1.13‐2.23) z‐score categories conferred an increased adjusted risk for active asthma. The likelihood ratio test (LRT) of nonlinearity yielded significant results (P < 0.01) for BF%. In contrast, the LRT for BMI yielded a nonsignificant result (P = 0.45) indicating a linear association of asthma with BMI. A unit increase in BMI z‐score conferred an increase in the adjusted odds of active asthma (OR: 1.14, 95% CI: 1.02‐1.27). In the case of BF%, the adjusted ORs for active asthma at the highest and lowest z‐score categories in both genders, before and during adolescence, were similarly elevated, exhibiting a U‐shape pattern.

Conclusions

In contrast to the linear association observed with BMI, BF% displayed a U‐shaped association with asthma and may be the preferred measure of adiposity in epidemiological studies of asthma in children.
Knockdown of diacylglycerol kinase delta inhibits adipocyte differentiation and alters lipid synthesis
Authors: Lowe Christopher E. , Zhang Qifeng , Dennis Rowena J. , Aubry Evelyne M. , O'Rahilly Stephen , Wakelam Michael J.O. , Rochford Justin J.
Published: January 2013

Objective

Decreased expression of diacylglycerol kinase delta (DGKδ) has been linked to insulin resistance in humans and mice and it is abundantly expressed in adipose tissue. Therefore, its role in adipogenesis was examined.

Design and Methods

3T3‐L1 pre‐adipocytes were generated in which DGKδ expression had been knocked down and the effect of this on adipogenesis was determined. Lipidomic analyses were performed to determine levels of the DGKδ product phosphatidic acid (PA), its substrate diacylglycerol (DAG) and triglyceride (TG).

Results

Inhibiting DGKδ expression prevents adipogenesis. DGKδ knockdown in differentiating adipocytes blunted the increase in total levels of PA and DAG but did not affect the early rise in TG levels. DAG or PA species acting as TG precursors were only modestly reduced by DGKδ knockdown which significantly impaired the accumulation of DAG or PA species implicated in intracellular signaling. The DAG activated kinase PKCδ was also stimulated in DGKδ knockdown cells, despite no increase in detectable species of DAG.

Conclusions

DGKδ is a novel regulator of adipogenesis and phosphorylates a quantitatively small pool of signaling DAG important for differentiation and indirectly affects overall levels of signaling DAG and PA species distinct from those acting as precursors for TG synthesis.
The relationship between measures of obesity and incident heart failure: The multi‐ethnic study of atherosclerosis
Authors: Ebong Imo A. , Goff David C. , Rodriguez Carlos J. , Chen Haiying , Bluemke David A. , Szklo Moyses , Bertoni Alain G.
Published: January 2013

Objective: To evaluate the strength of association of body mass index (BMI) and waist circumference (WC) with incident heart failure (HF), exploring our associations by ethnicity and age.

Design and Methods: 6,809 participants, aged 45‐84 years old, without clinical cardiovascular disease (2000–2002), from the Multi‐Ethnic Study of Atherosclerosis were included. Cox‐Proportional hazards models were used to examine associations of BMI and WC with incident HF. The predictive abilities of BMI and WC were compared using receiver operating characteristic curves.

Results: Over a median follow‐up of 7.6 years, there were 176 cases. BMI and WC were associated with incident HF in men (1.33 [1.10‐1.61] and 1.38 [1.18‐1.62], respectively] and women (1.70 [1.33‐2.17] and 1.64 [1.29‐2.08], respectively). These associations became non‐significant after adjusting for obesity‐related conditions (hypertension, dysglycemia, hypercholesterolemia, left ventricular hypertrophy, kidney disease, and inflammation). The associations of BMI and WC did not vary significantly by ethnicity or age‐group, but were inverse in Hispanic men. The area under the curve for BMI and WC was 0.749 and 0.750, respectively, in men and 0.782 and 0.777, respectively, in women.

Conclusions: The association between obesity and incident HF is largely mediated by obesity‐related conditions. BMI and WC have similar predictive abilities for incident HF.
Crosslinked PVAL nanofibers with enhanced long‐term stability prepared by single‐step electrospinning
Authors: Nugroho Robertus Wahyu N. , Roy Prasun Kumar , Odelius Karin , Albertsson Ann‐Christine
Published: December 2012

We present a single‐step route for the preparation of crosslinked poly(vinyl alcohol) (PVAL) nanofibers where a conventional electrospinning setup can be used. The simple crosslinking chemistry and the fast and easily applicable technique is an important step towards large‐scale production. In contrast to conventional systems, the PVAL crosslinker solution exhibited no increase in viscosity during storage and can therefore be used even after long shelf‐times before electrospinning. In addition, the crosslinked nanofibrous mats exhibited a gel content of almost 100%, indicating complete crosslinking; they did not dissolve in water, and no PVAL was found in the aqueous extract. The E‐moduli of the nanofibrous mats before and after water immersion could be measured by an intermodulation atomic force microscopy technique. A denser nanofibrous texture with enhanced mechanical properties can be observed after long‐term water immersion. Copyright © 2012 John Wiley & Sons, Ltd.
Increased autophagy in the placental territory of selective intrauterine growth‐restricted monochorionic twins
Authors: Chang Yao‐Lung , Wang Tzu‐Hao , Chang Shuenn‐Dyh , Chao An‐Shine , Hsieh Peter C. C. , Wang Chao‐Nin
Published: January 2013

Subject

This study investigates the placental autophagic activity in growth‐restricted fetuses in the monochorionic (MC) twin model.

Patients and methods

Forty MC twins were prospectively enrolled in this study, including 21 with and 19 without selective intrauterine growth restriction (sIUGR), defined as birth weight below the tenth percentile. The sIUGR group was subdivided on the basis of present versus absent or reversed umbilical artery end‐diastolic flow at Doppler. Placenta samples were taken after delivery from each twin placenta territories. After protein extraction, Western blot was used to determine light chain 3 (LC3)‐II placental protein expression in sIUGR and appropriately grown (appropriate‐for‐gestational age, AGA) twins.

Results

The LC3‐II was significantly higher in the sIUGR twin placental territory than in their AGA counterparts. In the sIUGR group, LC3‐II fold change was significantly increased compared with that in the AGA cotwins (2.28 vs 1.04, p < 0.05). Placental LC3‐II protein expression was particularly stimulated in the MC sIUGR group with abnormal umbilical artery Doppler flow compared with AGA controls (p < 0.05, one‐way analysis of variance test).

Conclusions

In MC twins, the placental autophagic activity is different between sIUGR and AGA cotwins. The placenta territory with the least blood flow perfusion has the highest autophagic activity. © 2013 John Wiley & Sons, Ltd.
A review of pharmaceutical labeling for overdose treatment and toxicity data
Authors: Mazer‐Amirshahi Maryann , Sokol Gerald , van den Anker John , Cantilena Louis
Published: January 2013

Purpose

Adverse drug reactions, including overdose are a major cause of morbidity and mortality, yet clinical toxicology data is limited at the time of drug approval. This study was conducted to determine the quality of clinical toxicology data available for newly approved pharmaceuticals and time to labeling revisions.

Methods

The labeling data of 100 new molecular entities (NMEs) approved between 2005 and 2011 was systematically reviewed. Initial approval data and subsequent labeling revisions were evaluated. The type and quality of clinical toxicology data present at the time of approval as well as the time to any labeling revisions was recorded. The presence of black box warnings and Risk Evaluation and Mitigation Strategies (REMS) was noted.

Results

Of the NMEs reviewed, 27 had agent‐specific toxicology data at approval. General recommendations for overdose management were made in 45 cases. Eight pharmaceuticals had toxicology updates during the study period. The average time to labeling revision was 27.4 months. Expanded adverse effects from case reports comprised 7/8 of the updates, and animal data was added in one case. Over a third of the NMEs had a black box warning or REMS status, suggesting potential for significant human toxicity.

Conclusions

Our study suggests there is a paucity of clinical toxicology data at the time of drug approval, with a notable lag time between initial approval and labeling revisions. This lack of toxicology data limits the ability of providers to optimally care for poisoned patients. Copyright © 2013 John Wiley & Sons, Ltd.
Quantitative local L2‐gain and Reachability analysis for nonlinear systems
Authors: Summers Erin , Chakraborty Abhijit , Tan Weehong , Topcu Ufuk , Seiler Pete , Balas Gary , Packard Andrew
Published: January 2013

This paper develops theoretical and numerical tools for quantitative local analysis of nonlinear systems. Specifically, sufficient conditions are provided for bounds on the reachable set and L2 gain of the nonlinear system subject to norm‐bounded disturbance inputs. The main theoretical results are extensions of classical dissipation inequalities but enforced only on local regions of the state and input space. Computational algorithms are derived from these local results by restricting to polynomial systems, using convex relaxations, for example the S‐procedure, and applying sum‐of‐squares optimizations. Several pedagogical and realistic examples are provided to illustrate the proposed approach. Copyright © 2013 John Wiley & Sons, Ltd.
Random non‐crossing plane configurations: A conditioned Galton‐Watson tree approach
Authors: Curien Nicolas , Kortchemski Igor
Published: December 2012

We study various models of random non‐crossing configurations consisting of diagonals of convex polygons, and focus in particular on uniform dissections and non‐crossing trees. For both these models, we prove convergence in distribution towards Aldous’ Brownian triangulation of the disk. In the case of dissections, we also refine the study of the maximal vertex degree and validate a conjecture of Bernasconi, Panagiotou and Steger. Our main tool is the use of an underlying Galton‐Watson tree structure. © 2014 Wiley Periodicals, Inc. Random Struct. Alg., 45, 236–260, 2014
XAFS analysis of indium oxynitride thin films grown on silicon substrates
Authors: Amnuyswat K. , Saributr C. , Thanomngam P. , Sungthong A. , Porntheeraphat S. , Sopitpan S. , Nukeaw J.
Published: December 2012

Local structure of indium oxynitride thin films grown on silicon substrates was investigated by X‐ray absorption fine structure technique incorporated with first principle calculations. The thin films were grown by using reactive gas timing radio frequency (RF) magnetron sputtering technique with nitrogen (N2) and oxygen (O2) as reactive gasses. The reactive gasses were interchangeably fed into sputtering system at five different time intervals. The gas feeding time intervals of N2:O2 are 30 : 0, 30 : 5, 30 : 10, 30 : 20 and 10 : 30 s, respectively. The analysis results can be divided into three main categories. Firstly, the films grown with 30 : 0 and 30 : 5 s gas feeding time intervals are wurtzite structure indium nitride with 25 and 43% oxygen contaminations, respectively. Secondary, the film grown with 10 : 30 s gas feeding time intervals is bixbyite structure indium oxide. Finally, the films are alloying between indium nitride and indium oxide for other growth condition. The fitted radial distribution spectra, the structural parameters and the combination ratios of the alloys are discussed. Copyright © 2012 John Wiley & Sons, Ltd.
Gestational protein restriction induces CA3 dendritic atrophy in dorsal hippocampal neurons but does not alter learning and memory performance in adult offspring
Authors: Lopes A. , Torres D.B. , Rodrigues A.J. , Cerqueira J.J. , Pêgo J.M. , Sousa N. , Gontijo J.A.R. , Boer P.A.
Published: December 2012

Studies have demonstrated that nutrient deficiency during pregnancy or in early postnatal life results in structural abnormalities in the offspring hippocampus and in cognitive impairment. In an attempt to analyze whether gestational protein restriction might induce learning and memory impairments associated with structural changes in the hippocampus, we carried out a detailed morphometric analysis of the hippocampus of male adult rats together with the behavioral characterization of these animals in the Morris water maze (MWM). Our results demonstrate that gestational protein restriction leads to a decrease in total basal dendritic length and in the number of intersections of CA3 pyramidal neurons whereas the cytoarchitecture of CA1 and dentate gyrus remained unchanged. Despite presenting significant structural rearrangements, we did not observe impairments in the MWM test. Considering the clear dissociation between the behavioral profile and the hippocampus neuronal changes, the functional significance of dendritic remodeling in fetal processing remains undisclosed.