bluuebunny/crossref_metadata_2025 huggingface dataset:
A review of the developments of characteristics of PEI derivatives for gene delivery applications
Authors: Taranejoo Shahrouz , Liu Jun , Verma Paul , Hourigan Kerry
Published: March 2015

Redox‐active stimuli have gained a great deal of interest as an indicating factor for designing bioresponsive matrices in gene delivery. Hence, a wide range of gene carriers has been designed incorporating the redox‐stimuli characteristics. The most important type of gene carriers is the class of redox responsive polymers. Among them, disulfide incorporated redox‐responsive polyethyleneimine (PEI) and its derivatives, as a result of their outstanding DNA entrapping characteristics and their intrinsic endosomolytic activity, have attracted considerable attention in recent studies. The review presents the main developments of the characteristics of PEI derivatives and their applications in gene delivery. It is found that despite the uniquely stated characteristics, the noncleavable structure of conventional PEI (high molecular weight PEI: 25k), which makes it a nondegradable material, as well as the frequent inclusion of positively charged amino groups, which reduces its blood circulation period, render conventional PEI a very toxic material for gene‐delivery applications. The extremely high cellular toxicity of conventional PEI has restricted its administration for real in‐vivo physiological media. Recent studies have shown that employing low molecular weight PEI cross‐linked by disulfide linkages (SS‐PEI) and assembling low molecular weight disulfide linkages PEI (LMW SS‐PEI) with bio‐detachable anionic groups were two successful approaches for increasing bioavailability of the PEI‐based gene carriers, while keeping outstanding cellular transfection. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42096.
CanAmazon.com reviews help to assess the wider impacts of books?
Authors: Kousha Kayvan , Thelwall Mike
Published: March 2015

Although citation counts are often used to evaluate the research impact of academic publications, they are problematic for books that aim for educational or cultural impact. To fill this gap, this article assesses whether a number of simple metrics derived fromAmazon.com reviews of academic books could provide evidence of their impact. Based on a set of 2,739 academic monographs from 2008 and a set of 1,305 best‐selling books in 15Amazon.com academic subject categories, the existence of significant but low or moderate correlations between citations and numbers of reviews, combined with other evidence, suggests that online book reviews tend to reflect the wider popularity of a book rather than its academic impact, although there are substantial disciplinary differences. Metrics based on online reviews are therefore recommended for the evaluation of books that aim at a wide audience inside or outside academia when it is important to capture the broader impacts of educational or cultural activities and when they cannot be manipulated in advance of the evaluation.
Institutional and individual factors affecting scientists' data‐sharing behaviors: A multilevel analysis
Authors: Kim Youngseek , Stanton Jeffrey M.
Published: March 2015

The objective of this research was to investigate the institutional and individual factors that influence scientists' data‐sharing behaviors across different scientific disciplines. Two theoretical perspectives, institutional theory, and theory of planned behavior, were employed in developing a research model that showed the complementary nature of the institutional and individual factors influencing scientists' data‐sharing behaviors. This research used a survey method to examine to what extent those institutional and individual factors influence scientists' data‐sharing behaviors in a range of scientific disciplines. A national survey (with 1,317 scientists in 43 disciplines) showed that regulative pressure by journals, normative pressure at a discipline level, and perceived career benefit and scholarly altruism at an individual level had significant positive relationships with data‐sharing behaviors, and that perceived effort had a significant negative relationship. Regulative pressure by funding agencies and the availability of data repositories at a discipline level and perceived career risk at an individual level were not found to have any significant relationships with data‐sharing behaviors.
How to count chromosomes in a cell: An overview of current and novel technologies
Authors: Bakker Bjorn , van den Bos Hilda , Lansdorp Peter M. , Foijer Floris
Published: March 2015

Aneuploidy, an aberrant number of chromosomes in a cell, is a feature of several syndromes associated with cognitive and developmental defects. In addition, aneuploidy is considered a hallmark of cancer cells and has been suggested to play a role in neurodegenerative disease. To better understand the relationship between aneuploidy and disease, various methods to measure the chromosome numbers in cells have been developed, each with their own advantages and limitations. While some methods rely on dividing cells and thus bias aneuploidy rates to that population, other, more unbiased methods can only detect the average aneuploidy rates in a cell population, cloaking cell‐to‐cell heterogeneity. Furthermore, some techniques are more prone to technical artefacts, which can result in over‐ or underestimation of aneuploidy rates. In this review, we provide an overview of several “traditional” karyotyping methods as well as the latest high throughput next generation sequencing karyotyping protocols with their respective advantages and disadvantages.
Modification of luminescence spectra of CaF2: Eu2+
Authors: Singh Vartika S. , Joshi C. P. , Moharil S. V. , Muthal P. L. , Dhopte S. M.
Published: March 2015

CaF2:Eu2+ is a well known phosphor having efficient excitation in the near ultraviolet (NUV) range. Phosphors with NUV excitation are required in newly emerging applications such as photoluminescence liquid crystal displays (PLLCD), solid‐state lighting (SSL), and down‐conversion for solar cells. However, emission of CaF2:Eu2+ is around 424 nm. Eye sensitivity drops considerably at these wavelengths. It is thus not useful for display applications for which emission in one of the primary colours (blue – 450 nm, green – 540 nm or red – 610 nm) is required. Efforts were made to modify the Photoluminescence (PL) spectra of CaF2:Eu2+ to meet these requirements using co‐dopants. A Ca0.49Sr0.50Eu0.01F2 phosphor showing better colour coordinates and having an emission maximum around 440 nm was discovered during these studies. Copyright © 2015 John Wiley & Sons, Ltd.
Study on the interaction of a cyanine dye with human serum transferrin
Authors: Zhang Xiu‐feng , Chen Lei , Yang Qian‐fan , Li Qian , Sun Xiao‐ran , Chen Hong‐bo , Yang Guang , Tang Ya‐lin
Published: March 2015

Complexation between the primary carrier of ligands in blood plasma, human serum transferrin (Tf), and a cyanine dye, 3,3′‐di(3‐sulfopropyl)‐4,5,4′,5′‐dibenzo‐9‐phenyl‐thiacarbocyanine‐triethylam monium salt (PTC) was investigated using fluorescence spectra, UV/Vis absorption spectra, synchronous fluorescence spectra, circular dichroism (CD) and molecular dynamic docking. The experimental results demonstrate that the formation of PTC–Tf complex is stabilized by van der Waal's interactions and hydrogen bonds, and the binding constants were found to be 8.55 × 106, 8.19 × 106 and 1.75 × 104 M−1. Moreover, fluorescence experiments prove that the operational mechanism for the fluorescence quenching is static quenching and non‐radiative energy transfer. Structural investigation of the PTC–Tf complexes via synchronous fluorescence spectra and CD showed that the structure of Tf became more stable with a major increase in the α‐helix content and increased polarity around the tryptophan residues after PTC binding. In addition, molecular modeling highlights the residues located in the N‐lobe, which retain high affinity for PTC. The mode of action of the PTC–Tf complex is illustrated by these results, and may provide an effective pathway for the transport and targeted delivery of antitumor agents. Copyright © 2015 John Wiley & Sons, Ltd.
Study on interactions of aminoglycoside antibiotics with calf thymus DNA and determination of calf thymus DNA via the resonance Rayleigh scattering technique
Authors: Qiao Man , Li Chunyan , Shi Ying , Liu Shaopu , Liu Zhongfang , Hu Xiaoli
Published: March 2015

A simple and sensitive resonance Rayleigh scattering (RRS) spectra method was developed for the determination of calf thymus DNA (ctDNA). The enhanced RRS signals were based on the interactions between ctDNA and aminoglycoside antibiotics (AGs) including kanamycin (KANA), tobramycin (TOB), gentamicin (GEN) and neomycin (NEO) in a weakly acidic medium (pH 3.3–5.7). Parameters influencing the method were investigated. Under optimum conditions, increments in the scattering intensity (∆I) were directly proportional to the concentration of ctDNA over certain ranges. The detection limit ranged from 12.2 to 16.9 ng/mL. Spectroscopic methods, including RRS spectra, absorption spectra and circular dichroism (CD) spectroscopy, coupled with thermo‐denaturation experiments were used to study the interactions, indicating that the interaction between AGs with ctDNA was electrostatic binding mode. Copyright © 2015 John Wiley & Sons, Ltd.
Heat shock protein 27 overexpression in CHO cells modulates apoptosis pathways and delays activation of caspases to improve recombinant monoclonal antibody titre in fed‐batch bioreactors
Authors: Tan Janice G.L. , Lee Yih Yean , Wang Tianhua , Yap Miranda G. S. , Tan Tin Wee , Ng Say Kong
Published: March 2015

CHO cells are major production hosts for recombinant biologics including the rapidly expanding recombinant monoclonal antibodies (mAbs). Heat shock protein 27 (HSP27) expression was observed to be down‐regulated towards the late‐exponential and stationary phase of CHO fed‐batch bioreactor cultures, whereas HSP27 was found to be highly expressed in human pathological cells and reported to have anti‐apoptotic functions. These phenotypes suggest that overexpression of HSP27 is a potential cell line engineering strategy for improving robustness of CHO cells. In this work, HSP27 was stably overexpressed in CHO cells producing recombinant mAb and the effects of HSP27 on cell growth, volumetric production titer and product quality were assessed. Concomitantly, HSP27 anti‐apoptosis functions in CHO cells were investigated. Stably transfected clones cultured in fed‐batch bioreactors displayed 2.2‐fold higher peak viable cell density, delayed loss of culture viability by two days and 2.3‐fold increase in mAb titer without affecting the N‐glycosylation profile, as compared to clones stably transfected with the vector backbone. Co‐immunoprecipitation studies revealed HSP27 interactions with Akt, pro‐caspase 3 and Daxx and caspase activity profiling showed delayed increase in caspase 2, 3, 8 and 9 activities. These results suggest that HSP27 modulates apoptosis signaling pathways and delays caspase activities to improve performance of CHO fed‐batch bioreactor cultures.
Doing that thing that scientists do: A discovery‐driven module on protein purification and characterization for the undergraduate biochemistry laboratory classroom
Authors: Garrett Teresa A. , Osmundson Joseph , Isaacson Marisa , Herrera Jennifer
Published: March 2015

In traditional introductory biochemistry laboratory classes students learn techniques for protein purification and analysis by following provided, established, step‐by‐step procedures. Students are exposed to a variety of biochemical techniques but are often not developing procedures or collecting new, original data. In this laboratory module, students develop research skills through work on an original research project and gain confidence in their ability to design and execute an experiment while faculty can enhance their scholarly pursuits through the acquisition of original data in the classroom laboratory. Students are prepared for a 6–8 week discovery‐driven project on the purification of the Escherichia coli cytidylate kinase (CMP kinase) through in class problems and other laboratory exercises on bioinformatics and protein structure analysis. After a minimal amount of guidance on how to perform the CMP kinase in vitro enzyme assay, SDS‐PAGE, and the basics of protein purification, students, working in groups of three to four, develop a protein purification protocol based on the scientific literature and investigate some aspect of CMP kinase that interests them. Through this process, students learn how to implement a new but perhaps previously worked out procedure to answer their research question. In addition, they learn the importance of keeping a clear and thorough laboratory notebook and how to interpret their data and use that data to inform the next set of experiments. Following this module, students had increased confidence in their ability to do basic biochemistry techniques and reported that the “self‐directed” nature of this lab increased their engagement in the project. © 2015 by The International Union of Biochemistry and Molecular Biology, 43(3):145–153, 2015.
Green Practices and Organizational Design as Sources of Strategic Flexibility and Performance
Authors: Perez‐Valls Miguel , Cespedes‐Lorente Jose , Moreno‐Garcia Juan
Published: March 2015

Green competences are dynamic capabilities based on practices (green practices), routines and structures that can be used to detect opportunities, make the most of them and use them to transform organizations. With this in mind, we explore the relationships between environmental management, organizational performance, and organizational processes and practices. We identify three key constructs related to green competences: (1) hybrid structures, (2) environmental best practices and (3) strategic flexibility, a key variable connecting structural design and green practices to organizational performance. We propose that the implementation of specific organizational structures characterized by the inclusion of market‐driven control practices within hierarchies (internal hybrids) could enhance firms' environmental responsiveness and deployment of green best practices. In addition, we suggest that green practices and structures are positively related to the development of strategic flexibility, driving above‐average returns in dynamic environments. To test these hypotheses, we use data from the European aviation industry. Copyright © 2015 John Wiley & Sons, Ltd and ERP Environment
Bilateral cleft lip and palate: A morphometric analysis of facial skeletal form using cone beam computed tomography
Authors: Starbuck John M. , Ghoneima Ahmed , Kula Katherine
Published: March 2015

Bilateral cleft lip and palate (BCLP) is caused by a lack of merging of maxillary and nasal facial prominences during development and morphogenesis. BCLP is associated with congenital defects of the oronasal facial region that can impair ingestion, mastication, speech, and dentofacial development. Using cone beam computed tomography (CBCT) images, 7‐ to 18‐year old individuals born with BCLP (n = 15) and age‐ and sex‐matched controls (n = 15) were retrospectively assessed. Coordinate values of three‐dimensional facial skeletal anatomical landmarks (n = 32) were measured from each CBCT image. Data were evaluated using principal coordinates analysis (PCOORD) and Euclidean Distance Matrix Analysis (EDMA). PCOORD axes 1–3 explain approximately 45% of the morphological variation between samples, and specific patterns of morphological differences were associated with each axis. Approximately, 30% of facial skeletal measures significantly differ by confidence interval testing (α = 0.10) between samples. While significant form differences occur across the facial skeleton, strong patterns of differences are localized to the lateral and superioinferior aspects of the nasal aperture. In conclusion, the BCLP deformity significantly alters facial skeletal morphology of the midface and oronasal regions of the face, but morphological differences were also found in the upper facial skeleton and to a lesser extent, the lower facial skeleton. This pattern of strong differences in the oronasal region of the facial skeleton combined with differences across the rest of the facial complex underscores the idea that bones of the craniofacial skeleton are integrated. Clin. Anat. 28:584–592, 2015. © 2015 Wiley Periodicals, Inc.
Dual Soft‐Template System Based on Colloidal Chemistry for the Synthesis of Hollow Mesoporous Silica Nanoparticles
Authors: Li Yunqi , Bastakoti Bishnu Prasad , Imura Masataka , Tang Jing , Aldalbahi Ali , Torad Nagy L. , Yamauchi Yusuke
Published: March 2015

A new dual soft‐template system comprising the asymmetric triblock copolymer poly(styrene‐b‐2‐vinyl pyridine‐b‐ethylene oxide) (PS‐b‐P2VP‐b‐PEO) and the cationic surfactant cetyltrimethylammonium bromide (CTAB) is used to synthesize hollow mesoporous silica (HMS) nanoparticles with a center void of around 17 nm. The stable PS‐b‐P2VP‐b‐PEO polymeric micelle serves as a template to form the hollow interior, while the CTAB surfactant serves as a template to form mesopores in the shells. The P2VP blocks on the polymeric micelles can interact with positively charged CTA+ ions via negatively charged hydrolyzed silica species. Thus, dual soft‐templates clearly have different roles for the preparation of the HMS nanoparticles. Interestingly, the thicknesses of the mesoporous shell are tunable by varying the amounts of TEOS and CTAB. This study provides new insight on the preparation of mesoporous materials based on colloidal chemistry.
Ein neuer Ansatz zur Charakterisierung der Flüssigphasenadsorption an Aktivkohlen
Authors: Treese Julian , Pasel Christoph , Luckas Michael , Bathen Dieter
Published: March 2015

Aktivkohlen sind industriell häufig eingesetzte Adsorbentien. Die Charakterisierung ihrer Oberflächeneigenschaften bereitet jedoch aufgrund der Vielzahl an Rohstoffen und Herstellungsvarianten Probleme. Hier wird eine Modellvorstellung zur Beschreibung der Oberfläche hergeleitet, die auf der Kenntnis der wesentlichen chemischen Wechselwirkungen auf Aktivkohleoberflächen basiert, die bereits erforscht wurden. An verschiedenen Aktivkohlen werden Adsorptionsisothermen ausgesuchter Probemoleküle vermessen und mit den Daten überprüft, inwiefern das Modell zur Bewertung der Oberflächenchemie von Aktivkohlen geeignet ist.
Stabilitätsanalyse mehrphasiger Strömungen in Mikrokanälen
Authors: Antweiler Nicolai , Munera Parra Alejandro A. , Agar David W.
Published: March 2015

Die Durchführung von mehrphasigen Reaktionen und Extraktionen in Mikrokanälen ermöglicht eine Intensivierung chemischer Prozesse. Eine Übertragung dieser Technologie in den industriellen Maßstab erfordert Strategien zur Skalierung ohne Maßstabsänderung. In dieser Arbeit findet eine Stabilitätsanalyse mehrphasiger Strömungen in Mikrokanälen statt. Es wird eine Gas/Flüssig‐Strömung modelliert und die Druckverlustdynamik in Abhängigkeit von Strömungs‐ und Stoffeigenschaften analysiert. Für mögliche Strategien zur Parallelisierung machen diese Ergebnisse auf die Notwendigkeit eines aktiven Regelkonzeptes aufmerksam.
Laparoscopic liver resection
Authors: Geller David A. , Khreiss Mohammad
Published: March 2015

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New treatments for HCV: Perspective from Asia
Authors: Yu Ming‐Lung , Chuang Wan‐Long
Published: March 2015

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Management patterns and predictors of mortality among US patients with cancer hospitalized for malignant bowel obstruction
Authors: Alese Olatunji B. , Kim Sungjin , Chen Zhengjia , Owonikoko Taofeek K. , El‐Rayes Bassel F.
Published: March 2015

BACKGROUND

Malignant bowel obstruction affects an estimated 3% to 15% of patients with cancer, with a mean survival of <4 weeks reported in patients with inoperable malignant bowel obstruction. In the current study, the authors assessed predictors of survival and the influence of treatment modality in US patients with cancer who were hospitalized for malignant bowel obstruction.

METHODS

All the US cancer patients hospitalized with malignant bowel obstruction in 2006 and 2010 were included. Data were obtained from the Nationwide Inpatient Sample provided by the Agency for Healthcare Research and Quality. Malignant bowel obstruction diagnoses and treatment variables were identified using Clinical Classifications Software codes based on International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Univariate and multivariate analyses were performed with a logistic model, weighted chi‐square test, and a generalized linear model.

RESULTS

The authors identified 942,014 and 1,103,528 hospitalizations for malignant bowel obstruction in 2006 and 2010, respectively. Medical management, upper gastrointestinal obstruction, health insurance coverage, and obesity were found to be significantly associated with better hospital survival. Multivariate analysis also demonstrated significantly increased odds of death with male sex, advanced age, AJCC stage IV disease, multiple comorbid conditions (except acquired immunodeficiency syndrome), and weight loss. There were no significant differences with stratification based on the location and etiology of the obstruction (primary tumor vs metastatic).

CONCLUSIONS

Malignant bowel obstruction is a common cause of death in hospitalized patients with advanced cancer in the United States. The odds of death are especially high in older patients and those with concurrent medical illnesses. Lack of insurance coverage, significant weight loss, and surgical management also appear to be associated with higher mortality in this population. Cancer 2015;121:1772–1778. © 2015 American Cancer Society.
Three‐arm, randomized, phase 2 study of carboplatin and paclitaxel in combination with cetuximab, cixutumumab, or both for advanced non–small cell lung cancer (NSCLC) patients who will not receive bevacizumab‐based therapy: An Eastern Cooperative Oncology Group (ECOG) study (E4508)
Authors: Hanna Nasser H. , Dahlberg Suzanne E. , Kolesar Jill M. , Aggarwal Charu , Hirsch Fred R. , Ramalingam Suresh S. , Schiller Joan H.
Published: March 2015

BACKGROUND

Preclinical evidence supports the clinical investigation of inhibitors to the insulin‐like growth factor receptor (IGFR) and the epidermal growth factor receptor (EGFR) either alone or in combination as treatment for patients with non–small cell lung cancer (NSCLC).

METHODS

Patients with chemotherapy‐naïve, advanced NSCLC who had an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomized to receive carboplatin intravenously at an area under the plasma drug concentration‐time curve of 6.0 plus paclitaxel 200 mg/m2 intravenously on day 1 every 3 weeks combined with either intravenous cetuximab weekly (arm A), intravenous cixutumumab every 2 weeks (arm B), or both (arm C). Patients who had nonprogessing disease after 12 weeks of therapy were permitted to continue on maintenance antibody therapy until they developed progressive disease. The primary endpoint was progression‐free survival (PFS). The study design required 180 eligible patients and had 88% power to detect a 60% increase in median PFS for either comparison (arm A vs arm C or arm B vs arm C) using the log‐rank test.

RESULTS

From September 2009 to December 2010, 140 patients were accrued. The study was closed to accrual early because of an excessive number of grade 5 events reported on arms A and C. Thirteen patients died during treatment (6 patients on arm A, 2 patients on arm B, and 5 patients on arm C), including 9 within approximately 1 month of starting therapy. The estimated median PFS for arms A, B, and C were similar at 3.4 months, 4.2 months, and 4 months, respectively.

CONCLUSIONS

On the basis of the apparent lack of efficacy and excessive premature deaths, the current results do not support the continued investigation of carboplatin, paclitaxel, and cixutumumab either alone or in combination with cetuximab for patients with advanced NSCLC. Cancer 2015;121:2253–2261. © 2015 American Cancer Society.
2‐Heteroaryl‐[1,2,4]triazolo[1,5‐c]quinazoline‐5(6 H)‐thiones and Their S‐Substituted Derivatives: Synthesis, Spectroscopic Data, and Biological Activity
Authors: Bilyi Andrii K. , Antypenko Lyudmyla M. , Ivchuk Vitalii V. , Kamyshnyi Oleksandr M. , Polishchuk Natalya M. , Kovalenko Sergiy I.
Published: March 2015

In the continuing search for novel, biologically effective heterocyclic agents, several methods for the synthesis of 2‐heteroaryl‐[1,2,4]triazolo[1,5‐c]quinazoline‐5(6 H)‐thiones have been developed: thiolation of oxo derivatives, [5+1] cyclocondensation of [2‐(3‐heteroaryl‐[1,2,4]triazol‐5‐yl)phenyl]amines with carbon disulfide, potassium ethyl xanthogenate, or aryl isothiocyanates, and in situ reaction of 2‐isothiocyanatobenzonitrile with hydrazides. A series of N‐R‐2‐[(2‐heteroaryl‐[1,2,4]triazole‐[1,5‐c]quinazoline‐5‐yl)thio]acetamides were obtained by aminolysis of the corresponding acetic acids and alkylation of potassium thiolates with N‐R‐2‐chloroacetamides. It was established that some potassium thiolates, 4 a–4 d, 4 h, and 4 i, had high antibacterial activity against Staphylococcus aureus with a minimum inhibitory concentration of 12.5 μg mL−1 and minimum bactericidal concentration of 25 μg mL−1, which exceeded the values for trimethoprim. In addition, {2‐[3‐(1 H‐indole‐2‐yl)‐1 H‐1,2,4‐triazol‐5‐yl]phenyl}amine 2 i was investigated in the concentration range 100–0.01 μM at 59 lines of nine cancer cell types, and showed a mean effective concentration at 3.12–7.03 μM and cytotoxic effect at 15.56–67.38 μM. The possible mechanisms of activity were predicted by molecular docking studies to S. aureus dihydrofolate reductase and epidermal growth factor receptor kinase.
Simultaneous quantification of digoxin, digitoxin, and their metabolites in serum using high performance liquid chromatography‐tandem mass spectrometry
Authors: Bylda Caroline , Thiele Roland , Kobold Uwe , Volmer Dietrich A.
Published: March 2015

The aim of this work was the development of a liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method for simultaneous quantification of two cardiac glycosidic drugs in human serum, namely digoxin (DG) and digitoxin (DT), as well as several of their metabolites: digoxin‐bis‐digitoxose and digoxin‐mono‐digitoxose, digitoxin‐bis‐digitoxose and digitoxin‐mono‐digitoxose, digoxigenin, digitoxigenin, dihydrodigoxin and acetyl‐ and methyldigoxin. The assay also allowed for semi‐quantitative analysis of two structurally similar compounds, deslanoside and lanatoside. As internal standards, deuterated analogues were synthesized for some of the target analytes. Highly abundant proteins were initially removed by protein precipitation using zinc sulfate before samples were extracted by supported liquid extraction. Chromatographic separation was achieved on a pentafluorphenyl stationary phase prior to electrospray ionization triple quadrupole mass spectrometry in multiple reaction monitoring mode. The assay allowed quantification of the analytes with lower limits of quantification between 0.04 and 2.0 ng/mL. Linearity was shown over the range 0.16–9.5 ng/mL for DG and its metabolites, and 1.6–95 ng/mL for DT and its metabolites with correlation coefficients R>0.991. The quantification range was determined as 1.1–8.9 ng/mL for DG and its metabolites and 12–90 ng/mL for DT and its metabolites. Within this range, DG and DT were determined with an accuracy of ±2% and precision <7% RSD. Trueness was confirmed by analyzing native samples and comparing the results to values obtained by a certified analysis laboratory. In conclusion, the assay represents a useful reference method for immunoassay‐based digoxin and digitoxin tests, which are easily biased by the presence of metabolites of the target analytes or structurally similar substances. Copyright © 2015 John Wiley & Sons, Ltd.
An inducible offense: carnivore morph tadpoles induced by tadpole carnivory
Authors: Levis Nicholas A. , de la Serna Buzón Sofia , Pfennig David W.
Published: March 2015

Phenotypic plasticity is commonplace, and plasticity theory predicts that organisms should often evolve mechanisms to detect and respond to environmental cues that accurately predict future environmental conditions. Here, we test this prediction in tadpoles of spadefoot toads, Spea multiplicata. These tadpoles develop into either an omnivore ecomorph, which is a dietary generalist, or a carnivore ecomorph, which specializes on anostracan shrimp and other tadpoles. We investigated a novel proximate cue – ingestion of Scaphiopus tadpoles – and its propensity to produce carnivores by rearing tadpoles on different diets. We found that diets containing tadpoles from the genus Scaphiopus produced more carnivores than diets without Scaphiopus tadpoles. We discuss why Scaphiopus tadpoles are an excellent food source and why it is therefore advantageous for S. multiplicata tadpoles to produce an inducible offense that allows them to better utilize this resource. In general, such inducible offenses provide an excellent setting for investigating the proximate and evolutionary basis of phenotypic plasticity.
Dispersive Raman spectroscopy allows the identification and quantification of melanin types
Authors: Galván Ismael , Jorge Alberto
Published: March 2015

Melanins are the most prevalent pigments in animals and are involved in visual communication by producing colored traits that often evolve as intraspecific signals of quality. Identifying and quantifying melanins are therefore essential to understand the function and evolution of melanin‐based signals. However, the analysis of melanins is difficult due to their insolubility and the lack of simple methods that allow the identification of their chemical forms. We recently proposed the use of Raman spectroscopy as a simple, noninvasive technique that can be used to identify and quantify melanins in feathers and hairs. Contrarily, other authors later stated that melanins are characterized by a lack of defined Raman signals. Here, we use confocal Raman microscopy to confirm previous analyses showing that the two main chemical forms of melanins (eumelanin and pheomelanin) exhibit distinct Raman signal and compare different excitation wavelengths to analyze synthetic pheomelanin and natural melanins in feathers of different species of birds. Our analyses indicate that only laser excitation wavelengths below 1064 nm are useful for the analysis of melanins by Raman spectroscopy, and only 780‐nm laser in the case of melanins in feathers. These findings show that the capacity of Raman spectroscopy to distinguish different chemical forms of melanins depends on laser power and integration time. As a consequence, Raman spectroscopy should be applied after preliminar analyses using a range of these parameters, especially in fragile biological tissues such as feathers.
Glaciokarst landforms and processes of the southern Dinaric Alps
Authors: Žebre Manja , Stepišnik Uroš
Published: March 2015

Glaciokarst is a landscape which combines karst features and hydrology as well as inherited glacial features. It is a result of glaciation upon a karst geomorphological system. The relationship between glaciers and karst is rather poorly known and inadequately recognized. This research focuses on three distinct karst areas along the Adriatic coast in the southern Dinaric Alps that were affected by the Quaternary glaciations. An insight into specific glaciokarst processes and surface features was provided through the study of the areas of the Lovćen, Orjen and Velež Mountains. A glaciokarst geomorphology is in general well preserved due to the prevailing vertically oriented chemical denudation following de‐glaciation and almost the entire absence of other surface processes. Typical glacial erosional features are combined by a variety of depressions which are the result of a karstic drainage of sub‐glacial waters. The majority of glacial deposits occur as extensive lateral‐terminal moraine complexes, which are often dissected by smaller breach‐lobe moraines on the external side of the ridge. Those moraine complexes are likely to be a product of several glacial events, which is supported by complex depositional structures. According to the type of glacial depositional features, the glaciers in the study areas were likely to have characteristics of moraine‐dammed glaciers. Due to vertical drainage ice‐marginal fluvial processes were unable to evacuate sediment. Fluvial transport between glacial and pro‐glacial systems in karst areas is inefficient. Nevertheless, some sediment from the glacier margin is washed away by the pro‐glacial streams, filling the karst depressions and forming piedmont‐type poljes. Copyright © 2015 John Wiley & Sons, Ltd.
Behavior of beams in bolted column‐tree frames at elevated temperature
Authors: Yahyai Mahmood , Rezaeian Abbas
Published: March 2015

Column‐tree moment resisting frames, as the efficient shop‐welded and field‐bolted structural systems, are used in many countries. Very limited research has been carried out on such systems under fire conditions. This paper presents experimental and numerical investigations of the behavior of beam and bolted splice connections in steel column‐tree moment resisting frames exposed to fire. Two full‐scale steel sub‐frames with different splice connections were tested under International Organization for Standardization (ISO 834) fire. The observation of thermal and structural fire behaviors including temperature histories, temperature deflection of the beam, temperature rotation of splice connections, and failure modes was investigated. The beam splice connection failed because of shear fracture of top bolts at temperatures beyond 750 °C, while beam underwent large deflections of more than span/20. In addition, detailed 3‐D finite element models were developed to simulate the structural behavior of the specimens in fire. Obtained numerical results from the finite element analysis successfully simulated the experimental fire test results. Copyright © 2015 John Wiley & Sons, Ltd.
Risk of sensitization to fragrances estimated on the basis of patch test data and exposure, according to volume used and a sample of 5451 cosmetic products
Authors: Schnuch Axel , Uter Wolfgang , Lessmann Holger , Geier Johannes
Published: March 2015

The risk of sensitization cannot be derived from the frequency of sensitization to allergens alone, as exposure also should be considered. The occurrence of 26 fragrances in 5451 products based on the labelling of the ingredients was documented. Use volumes were provided by the International Fragrance Association (IFRA). Frequency of sensitization to fragrances was analysed based on IVDK data from September 2007 to December 2009. As an estimate of sensitization risk, the sensitization exposure quotient (SEQ) was calculated as the quotient of the relative frequency of sensitization and the relative frequency of use/labelling. The SEQs (the risk) varied greatly, offering a ranking regarding risk of sensitization: oak moss, tree moss, farnesol, methyl 2‐octynoate (methyl heptine carbonate) and isoeugenol at the top of the list indicating a (very) high risk of sensitization, butylphenyl methylpropional (Lilial ®), hexyl cinnamal, citronellol, linalool and limonene at the bottom, indicating a (very) low risk of sensitization. Compounds with a high risk were found to be classified as potent allergens according to the LLNA. High frequencies of sensitization may be put into perspective by the frequent use of certain fragrances. Despite infrequent use, others (with higher potencies or too high use concentrations) may turn out to be associated with an increased risk. Hazard assessment should be supplemented by risk assessment. Copyright © 2015 John Wiley & Sons, Ltd.
Simulation of viscoelastic fluids in a 2D abrupt contraction by spectral element method
Authors: Jafari Azadeh , Fiétier Nicolas , Deville Michel O.
Published: March 2015

This study presents the vortex structure and numerical instability increase occurring when the level of elasticity is enhanced in inertial flows in planar contraction configuration for finitely extensible nonlinear elastic model by Peterlin (FENE‐P) fluid . The re‐entrant corner effect on corner vortices is also considered. The calculations are performed using extended matrix logarithm formulation described in a previous paper: A. Jafari et al. A new extended matrix logarithm formulation for the simulation of viscoelastic fluids by spectral elements. Computer & Fluids 2010; 39(9):1425–1438. In that reference, the proposed algorithm has been tested for simple geometry such as Poiseuille flow. In this study, we are interested in the capability of this algorithm for more complex geometry. This formulation helps to reach higher values of the Weissenberg number when compared with the classical one. Copyright © 2015 John Wiley & Sons, Ltd.
Subduction initiation of Indochina and South China blocks: insight from the forearc ophiolitic peridotites of the Song Ma Suture Zone in Vietnam
Authors: Ngo Thanh Xuan , Santosh M. , Tran Hai Thanh , Pham Hieu Trung
Published: March 2015

The Song Ma region, which is located in the northwestern Vietnam represents the zone of amalgamation between Indochina and South China blocks. Numerous scattered ultramafic rocks occur in this region in association with Early to Middle Palaeozoic greenschists and paragneisses, and all these rocks were subjected to hydrous metamorphism and deformation. Here, we present new field data, mineral chemistry and geochemistry from a suite of hydrated peridotites within the Song Ma region and discuss the tectonic significances of the region. We also combine the available data within the Song Ma region and Indochina–South China blocks to discuss the tectonic evolution of the subduction zone. Based on the results, we suggest that the peridotites from the Song Ma are mantle residues that suffered a high degree of partial melting in a forearc tectonic setting. The present data together with the available data within the Song Ma region and the Indochina and South China blocks clearly represent a southward directed Middle Palaeozoic subduction system. The Middle Palaeozoic subduction and accretion events mark the evolutionary history along an active convergent margin between the Indochina and South China blocks, possibly related to the amalgamation of the Pangaea supercontinent. Copyright © 2015 John Wiley & Sons, Ltd.
World Health Organization Reform: Lessons Learned from the Ebola Epidemic
Authors: Gostin Lawrence O.
Published: March 2015

It was October 2014, and Ebola was raging out of control in Guinea, Liberia, and Sierra Leone. Margaret Chan, the World Health Organization's director‐general, defended the organization against charges that its response was late and ineffective: “We are a technical agency, with governments having first priority to take care of their people.” In January 2015, the WHO executive board undertook a systematic reform of the agency's performance, and Chan again offered a defense: I followed protocol, leaving it to the Africa office (AFRO) to respond. Yet the three nations could not possibly have stemmed the outbreak alone, and AFRO was known to be dysfunctional.

Ebola represents an inflection point requiring fundamental reform for the WHO. A failure of leadership will impact its status and legitimacy for a generation. Here, I offer five reforms that would transform it and ensure that it fulfills its constitutional mission as “the directing and coordinating authority on international health work.”
Temporizing after Spinal Cord Injury
Authors: Volpe Rebecca L. , Crites Joshua S. , Kirschner Kristi L.
Published: March 2015

Mr. C is a twenty‐two‐year‐old who was flown to a level‐1 trauma center after diving headfirst into shallow water. Prior to this accident, he was in excellent health. At the scene, he had been conscious but was paralyzed and had no sensation below his neck. The emergency medical services team immobilized Mr. C's neck with a cervical collar and intubated him for airway protection before transport. As Mr. C's medical care proceeds, he expresses a desire for extubation, although it was not clear that he had the capacity to make this (or any other) decision. It also was unclear whether this desire reflected his authentic wishes to be allowed to die or stemmed from feelings of discomfort and agitation. Over a period of several days, Mr. C's sedation was lightened, and the psychiatry service conducted a formal decision‐making capacity assessment. Mr. C continues to express a desire to withdraw life‐sustaining medical treatment. However, the psychiatry service is concerned that Mr. C seems to lack adequate insight into what it would mean to die.

What does it mean to respect Mr. C's autonomy?
Why It's Not Time for Health Care Rationing
Authors: Ubel Peter A.
Published: March 2015

In the last few years, the U.S. health care system has seemingly been gripped by “back to the nineties” fever. But there is a notable change in professional debates about how to better control health care costs. Discussion of health care rationing, which was hotly debated in the nineties, has become much more muted.

Is health care rationing passé? I contend that debates about health care rationing have waned not because the need to ration has dwindled nor because ethical debates about how or whether to ration have been resolved. They have declined because the word “rationing,” and unrelated concepts such as cost‐effectiveness analysis, have been replaced by terms—“parsimony,” “value,” and “CER”—that are not burdened by emotional and historical baggage.

Sometimes the best way to promote healthy moral debate is to turn to new words that don't carry the burden of past debates.
Translational Research May Be Most Successful When It Fails
Authors: Ioannidis John P. A.
Published: March 2015

In this issue of the Hastings Center Report, Jonathan Kimmelman and Alex London argue that in assessing the success of clinical translation, it is narrow‐minded to focus only on how many new drugs get licensed and how quickly they achieve licensure. Kimmelman and London show that clinical translation should be judged on its ability to generate as comprehensive an intervention ensemble as possible for the tested interventions. I would like to extend Kimmelman and London's position in two ways. First, I would argue that in the current environment, failures should be seen not just as acceptable, but probably as the most useful outcomes that translational research efforts can offer. Second, an intervention ensemble probably cannot be generated with information only about the drug or drugs produced by a single company. For most conditions and diseases, there are already a large number of other interventions whose use is supported or contradicted by various levels of evidence.
Thiophosphate/Phosphonate‐Containing Cross‐Linked PEGs and Their Use for the Stabilization of Silver Nanoparticles
Authors: Hameau Aurélien , Collière Vincent , Glaria Arnaud , Caminade Anne‐Marie , Turrin Cédric‐Olivier
Published: March 2015

A simple strategy was developed to obtain poly(ethylene glycol) (PEG)‐based materials incorporating phosphonate functions and thiophosphate groups from readily accessible symmetrical PEG compounds and trifunctional thiophosphates. These materials are obtained in a two‐step procedure, via the formation of THF soluble, hyperbranched PEG‐based polyazomethines that are subsequently functionalized with dimethylphosphite. The resulting materials are hydrolytically degradable, and upon exposure to aqueous solutions of silver acetate they afford stable colloidal solutions of silver.
Undergraduate Research and Its Impact on Student Success for Underrepresented Students
Authors: O'Donnell Ken , Botelho Judy , Brown Jessica , González Gerardo M. , Head William
Published: March 2015

This chapter captures the mission and spirit of the California State University in its efforts to institutionalize undergraduate research and support the success of students traditionally underrepresented in higher education.
Investigations of uncertainty in SWAT hydrologic simulations: a case study of a Canadian Shield catchment
Authors: Fu Congsheng , James April L. , Yao Huaxia
Published: March 2015

Uncertainty analysis is an integral part of hydrological modelling. We investigated uncertainty from model structure and parameters in the soil and water assessment tool (SWAT) hydrologic simulations for a Canadian Shield catchment (5.4 km2) in south central Ontario. We investigated influences of model structure on parameter identifiability and prediction uncertainty by comparing model performance of SWAT (version 2009.10.1 Beta3) and SWAT‐CS (a version representing hydrological processes in Canadian Shield catchments). Equifinality was found to exist for many parameters in process modules of snow water equivalent (SWE), streamflow and lake outflow. For SWAT, there are clearly identifiable parameters from process modules of snowmelt, overland flow, lateral flow and groundwater flow, while snowmelt parameters and lateral flow travel time are the only clearly identifiable parameters in SWAT‐CS. Model structure also notably influenced the optimum parameter values. Only 50–55% of observed SWE and 27–43% of observed streamflow were bracketed by the corresponding 95% confidence interval. The prediction uncertainty for SWE was mainly caused by the inaccuracy in timing of simulated snowmelt. This, along with use of a daily time step that is not able to capture the subdaily rainfall on snow pack, the limited capability of simulating groundwater by SWAT and the close‐to‐zero streamflow during dry seasons at the study catchment, could all contribute to the prediction uncertainty in streamflow. Comparatively, more reasonable model structure (SWAT‐CS) was shown to reduce prediction uncertainty. Copyright © 2015 John Wiley & Sons, Ltd.
Co-administration of Antiresorptive and Anabolic Agents: A Missed Opportunity
Authors: Seeman Ego , Martin T John
Published: March 2015

Co-administration of antiresorptive and anabolic therapies has appeal because these treatments target the two main abnormalities in bone remodeling responsible for bone loss and microstructural deterioration. Antiresorptives reduce the number of basic multicellular units (BMUs) remodeling bone and reduce the volume of bone each BMU resorbs. Intermittent parathyroid hormone (PTH) increases the volume of bone formed by existing BMUs and those generated by PTH administration. PTH also increases bone formation by stimulating the differentiation, maturation, and longevity of osteoblast lineage cells residing upon quiescent bone surfaces. Despite these rationally targeted actions, enthusiasm for this approach waned when combined therapy blunted the increase in areal bone mineral density (aBMD) relative to that produced by PTH. Although many studies have since reported additive effects of combined therapy, whatever the aBMD result (blunting, additive, or null), these outcomes give little, if any, insight into changes in bone's material composition or microstructure and give misleading information concerning the net effects on bone strength. Combined therapy remains a potentially valuable approach to therapy. Because studies of antifracture efficacy comparing combined with single therapy are unlikely to be performed in humans, efforts should be directed toward improving methods of quantifying the net effects of combined therapy on bone's material composition, microarchitecture, and strength. © 2015 American Society for Bone and Mineral Research.