bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia
Authors: Yamashita Atsuya , Salam Kazi Abdus , Furuta Atsushi , Matsuda Yasuyoshi , Fujita Osamu , Tani Hidenori , Fujita Yoshihisa , Fujimoto Yuusuke , Ikeda Masanori , Kato Nobuyuki , Sakamoto Naoya , Maekawa Shinya , Enomoto Nobuyuki , Nakakoshi Masamichi , Tsubuki Masayoshi , Sekiguchi Yuji , Tsuneda Satoshi , Akimitsu Nobuyoshi , Noda Naohiro , Tanaka Junichi , Moriishi Kohji
Published: March 2012

Hepatitis C virus (HCV) is a causative agent of acute and chronic hepatitis, leading to the development of hepatic cirrhosis and hepatocellular carcinoma. We prepared extracts from 61 marine organisms and screened them by an in vitro fluorescence assay targeting the viral helicase (NS3), which plays an important role in HCV replication, to identify effective candidates for anti-HCV agents. An ethyl acetate-soluble fraction of the feather star Alloeocomatella polycladia exhibited the strongest inhibition of NS3 helicase activity, with an IC50 of 11.7 µg/mL. The extract of A. polycladia inhibited interaction between NS3 and RNA but not ATPase of NS3. Furthermore, the replication of the replicons derived from three HCV strains of genotype 1b in cultured cells was suppressed by the extract with an EC50 value of 23 to 44 µg/mL, which is similar to the IC50 value of the NS3 helicase assay. The extract did not induce interferon or inhibit cell growth. These results suggest that the unknown compound(s) included in A. polycladia can inhibit HCV replication by suppressing the helicase activity of HCV NS3. This study may present a new approach toward the development of a novel therapy for chronic hepatitis C.
Epigenetic Tailoring for the Production of Anti-Infective Cytosporones from the Marine Fungus Leucostoma persoonii
Authors: Beau Jeremy , Mahid Nida , Burda Whittney N. , Harrington Lacey , Shaw Lindsey N. , Mutka Tina , Kyle Dennis E. , Barisic Betty , Van Olphen Alberto , Baker Bill J.
Published: March 2012

Recent genomic studies have demonstrated that fungi can possess gene clusters encoding for the production of previously unobserved secondary metabolites. Activation of these attenuated or silenced genes to obtain either improved titers of known compounds or new ones altogether has been a subject of considerable interest. In our efforts to discover new chemotypes that are effective against infectious diseases, including malaria and methicillin-resistant Staphylococcus aureus (MRSA), we have isolated a strain of marine fungus, Leucostoma persoonii, that produces bioactive cytosporones. Epigenetic modifiers employed to activate secondary metabolite genes resulted in enhanced production of known cytosporones B (1, 360%), C (2, 580%) and E (3, 890%), as well as the production of the previously undescribed cytosporone R (4). Cytosporone E was the most bioactive, displaying an IC90 of 13 µM toward Plasmodium falciparum, with A549 cytotoxicity IC90 of 437 µM, representing a 90% inhibition therapeutic index (TI90 = IC90 A459/IC90 P. falciparum) of 33. In addition, cytosporone E was active against MRSA with a minimal inhibitory concentration (MIC) of 72 µM and inhibition of MRSA biofilm at roughly half that value (minimum biofilm eradication counts, MBEC90, was found to be 39 µM).
1D 13C-NMR Data as Molecular Descriptors in Spectra — Structure Relationship Analysis of Oligosaccharides
Authors: Pereira Florbela
Published: March 2012

Spectra-structure relationships were investigated for estimating the anomeric configuration, residues and type of linkages of linear and branched trisaccharides using 13C-NMR chemical shifts. For this study, 119 pyranosyl trisaccharides were used that are trimers of the α or β anomers of D-glucose, D-galactose, D-mannose, L-fucose or L-rhamnose residues bonded through a or b glycosidic linkages of types 1→2, 1→3, 1→4, or 1→6, as well as methoxylated and/or N-acetylated amino trisaccharides. Machine learning experiments were performed for: (1) classification of the anomeric configuration of the first unit, second unit and reducing end; (2) classification of the type of first and second linkages; (3) classification of the three residues: reducing end, middle and first residue; and (4) classification of the chain type. Our previously model for predicting the structure of disaccharides was incorporated in this new model with an improvement of the predictive power. The best results were achieved using Random Forests with 204 di- and trisaccharides for the training set—it could correctly classify 83%, 90%, 88%, 85%, 85%, 75%, 79%, 68% and 94% of the test set (69 compounds) for the nine tasks, respectively, on the basis of unassigned chemical shifts.
Underwater Wireless Sensor Communications in the 2.4 GHz ISM Frequency Band
Authors: Lloret Jaime , Sendra Sandra , Ardid Miguel , Rodrigues Joel J. P. C.
Published: March 2012

One of the main problems in underwater communications is the low data rate available due to the use of low frequencies. Moreover, there are many problems inherent to the medium such as reflections, refraction, energy dispersion, etc., that greatly degrade communication between devices. In some cases, wireless sensors must be placed quite close to each other in order to take more accurate measurements from the water while having high communication bandwidth. In these cases, while most researchers focus their efforts on increasing the data rate for low frequencies, we propose the use of the 2.4 GHz ISM frequency band in these special cases. In this paper, we show our wireless sensor node deployment and its performance obtained from a real scenario and measures taken for different frequencies, modulations and data transfer rates. The performed tests show the maximum distance between sensors, the number of lost packets and the average round trip time. Based on our measurements, we provide some experimental models of underwater communication in fresh water using EM waves in the 2.4 GHz ISM frequency band. Finally, we compare our communication system proposal with the existing systems. Although our proposal provides short communication distances, it provides high data transfer rates. It can be used for precision monitoring in applications such as contaminated ecosystems or for device communicate at high depth.
Parametric Study of the Reflective Periodic Grating for In-Plane Displacement Measurement Using Optical Fibers
Authors: Lee Yeon-Gwan , Kim Dae-Hyun , Kim Chun-Gon
Published: March 2012

This paper presents a technique for a simple sensing principle that can be used for the measurement of displacement. The proposed sensor head is composed of a reflective grating panel and an optical fiber as a transceiver. The simplified layout contributes to resolving the issues of space restraints during installation and complex cabling problems in transmission fiber optic sensors. In order to verify the effectiveness of the proposed technique, it is important to obtain the sinusoidal signal reflected from the grating for reasonable phase tracking. In the numerical analysis, a real wave based optical beam model is proposed for the extraction of predicted signal according to the grating width and ratio of reflection bar width to spacing. The grating pattern design to obtain a sine wave reflected sensor signal was determined within an R-square value of 0.98 after sine curve fitting analysis. Consequently, the proposed sensor principle achieved the in-plane displacement measurement with a maximum accuracy error of 5.34 µm.
Application of Optical Biosensors in Small-Molecule Screening Activities
Authors: Geschwindner Stefan , Carlsson Johan F. , Knecht Wolfgang
Published: March 2012

The last two decades have seen remarkable progress and improvements in optical biosensor systems such that those are currently seen as an important and value-adding component of modern drug screening activities. In particular the introduction of microplate-based biosensor systems holds the promise to match the required throughput without compromising on data quality thus representing a sought-after complement to traditional fluidic systems. This article aims to highlight the application of the two most prominent optical biosensor technologies, namely surface plasmon resonance (SPR) and optical waveguide grating (OWG), in small-molecule screening and will present, review and discuss the advantages and disadvantages of different assay formats on these platforms. A particular focus will be on the specific advantages of the inhibition in solution assay (ISA) format in contrast to traditional direct binding assays (DBA). Furthermore we will discuss different application areas for both fluidic as well as plate-based biosensor systems by considering the individual strength of the platforms.
Moving towards Energy Self-Sufficiency Based on Renewables: Comparative Case Studies on the Emergence of Regional Processes of Socio-Technical Change in Germany
Authors: Hauber Jürgen , Ruppert-Winkel Chantal
Published: March 2012

The change of conventional energy systems to a system mainly based on renewable energies is occurring in many parts of the world. A processual analysis of three case studies from regions in Germany that are moving towards renewable energy self-sufficiency were conducted in order to better understand this process of socio-technical change. This paper scrutinizes the role of actors and their activities, which are driving the change of the local energy system. Three discrete distinguishable phases of this change were found: pioneer phase, pivotal network phase, and extended network and emerging market dynamic phase. Each phase can be characterized by the type of actor, their specific activities, artifacts involved, and their underlying motives. We suggest using the phase model as a heuristic instrument to identify the elements which shape socio-technical change.
The limitations of the constant load and self-paced exercise models of exercise physiology
Authors: Marino F.E.
Published: March 2012

The fundamental tenets of exercise physiology are to describe energy transformations during physical work and make predictions about physical performance during different conditions. Historically, the most popular method to observe such responses during exercise has been the constant load or fixed intensity protocol based largely on the assumption that there is a threshold response of the organism under given conditions. However, constant load exercise does not fully allow for randomness or variability as the biological system is overridden by a predetermined externally imposed load which cannot be altered. Conversely, in self-regulated (paced) exercise there is almost an immediate reduction in power output and muscle recruitment upon commencing exercise. This observation suggests the existence of a neural inhibitory command processes. This difference in regulation demonstrates the inherent importance of variability in the biological system; for in tightly controlled energy expenditure, as is the case during constant load exercise, sensory cues cannot be fully integrated to provide a more appropriate response to the given task. The collective evidence from conventional constant load versus self-regulated exercise studies suggest that energy transformations are indeed different so that the inherent biological variability accounts for the different results achieved by the two experimental paradigms.
Ultrasonographic measurement of spleen volume in horses
Authors: Navas de Solis C. , Foreman J.H. , Byron C.R. , Carpenter R.E.
Published: March 2012

Ante-mortemmeasurement of spleen size may be valuable to understand and study hemodynamic changes during exercise and in clinical determination of splenomegaly. The hypotheses were that spleen volume can be calculated from transcutaneous ultrasonographic measurements in live standing horses; and that the spleen volume is proportional to blood volume, maximal under the influence of detomidine and minimal under the influence of epinephrine. Eight donated horses free of splenic disease were studied. Ultrasonographic spleen volume and Evans blue dye-dilution blood volume were measured before (baseline) and after intravenous administration of detomidine and epinephrine (separately). Spleen volume was calculated using a standard ellipsoid formula (VOLstandard) and with the formula modified for the unique shape of the equine spleen (VOLmodified). Horses were euthanised using pentobarbital sodium, spleens removed immediately and measurements repeated on the removed spleen. Descriptive statistics, correlation and regression analysis were performed. Mean VOLstandardwas 31.4±9.8 litre at baseline, 34.0±10.5 litre after detomidine, and 5.4±3.1 litre after epinephrine. VOLmodifiedwas 25.1±9.1 litre at baseline, 27.4±9.6 litre after detomidine, and 4.2±2.4 litre after epinephrine.Post-mortemspleen volume was 14.1±4.6 litre and was correlated with VOLstandard(r=0.86,P=0.006) and VOLmodified(r=0.87,P=0.004). Blood volume was correlated with VOLstandard(r=0.81,P=0.014) and VOLmodified(r=0.78,P=0.02). Packed cell volume after epinephrine was correlated with VOLstandard(r=0.95,P<0.001) and VOLmodified(r=0.96,P<0.001). When compared to baseline, spleen volume was smaller after epinephrine (P=0.009) but not larger after detomidine (P=0.12). Blood volume after epinephrine was larger than after detomidine (P=0.009). The study demonstrated that splenic size, under various pharmacological influences, can be calculated from ultrasonographic measurements in the live standing horse. Packed cell volume after epinephrine was the best indicator of spleen volume.
La investigación-acción en la formación del profesorado
Authors: Romera-Iruela María Jesús
Published: March 2012

La investigación en la acción del profesor posibilita la mejora continua de la educación y la vinculación entre la teoría y la práctica. Esta investigación, si bien tiene tradición en la formación del profesorado, adquiere, en estos momentos, una gran relevancia, puesto que ha de preceder y seguir a las reformas educativas. El objetivo de esta investigación es identificar la trayectoria de la investigación-acción en la formación del profesorado, a través de los artículos publicados en las revistas españolas de educación. El diseño de la misma es de examen y utiliza la metodología documental. Los resultados dan a conocer la productividad de esta línea de investigación duran te todo su desarrollo, aportando una base de datos con todos los artículos, y muestran sus dimensiones personales, sociales y cognitivas: grado de colaboración en las publicaciones, autores más productivos, grupos de investigación, principales instituciones en la realización de trabajos, revistas propias de esta línea de investigación, principales temas estudiados y enfoques epistemológicos, entre otras variables consideradas.
Reseñas en revistas científicas españolas de Ciencias Sociales y Humanidades: análisis de la producción entre 2007 y 2009
Authors: Sorli Rojo Ángela , Mochón Bezares Gonzalo , Martín-Carretero Carolina
Published: March 2012

Se presenta un análisis bibliométrico de la producción de reseñas editadas en revistas científicas españolas de calidad en ciencias Sociales y Humanidades incluidas en la base de datos ISOC, y publicadas en los años 2007-2009. Se analizan: evolución temporal, revistas editoras, autoría y filiación institucional. También se examina la producción de libros reseñados según tipo documental, idioma de edición, autoría, entidad editora, y la duración del intervalo de tiempo entre edición de libro y reseña. Los resultados sobre reseñas indican un descenso constante en su producción, y un elevado número de documentos en humanidades. Los autores son en su mayoría profesores universitarios y españoles; publican solos; tienen una productividad muy baja; y un alto nivel de endogamia en aquellos autores que son miembros de Consejos de revista. Los resultados sobre libros reseñados demuestran que hay pocos títulos reseñados más de una vez, un elevado número de monografías, muchas en español, y un intervalo alto de tiempo entre la edición de los libros y su reseña.
Synthesis of chitosan stabilized silver nanoparticles using gamma ray irradiation and characterization
Authors: Hettiarachchi M.A. , Wickramarachchi P.A.S.R.
Published: March 2012

Chitosan stabilized silver nanoparticles (AgNPs) were synthesized using gamma ray irradiation. Four different sample solutions were prepared [1 mM AgNO3 in 0.1% (w/v) chitosan, 1 mM AgNO3 in 0.5% (w/v) chitosan, 2 mM AgNO3 in 0.1% (w/v) chitosan 2 mM AgNO3 in 0.5% (w/v) chitosan] with controls maintaining dose of radiation at 20±2 kGy. The formation of AgNPs were determined by the appearance of the characteristic colour of the AgNPs, using the surface plasmon resonance band (SPR) at 400-432 nm range and the N-H band of the FT-IR spectrum. Stability of the maximum absorption wave lengths of the samples was monitored for three months by UV-visible spectroscopy. The particle size distribution of the stabilized sample, showed a wide distribution of 28-1106 nm. The sample, 2 mM AgNO3 in 0.5% (w/v) chitosan was stable for three months. FT-IR spectroscopic analysis revealed a shifting of N-H stretching vibration band from 3367-3228 cm-1 with the introduction of nanoparticles. Keywords : Silver nanoparticles; Chitosan; Gamma ray irradiationDOI: http://dx.doi.org/10.4038/josuk.v6i0.4222J Sci.Univ.Kelaniya 6 (2011) : 65-75
Traumatic Pseudoaneurysm of the Superficial Temporal Artery
Authors: Manuel Suvy , Simon Deepti , George Eldhose K. , Naik Raghava B.
Published: March 2012

Aneurysms of the superficial temporal artery are relatively rare vascular complications following trauma. Two cases of pseudoaneurysm of the anterior branch of the superficial temporal artery, subjected to blunt maxillofacial trauma are presented here. The first case was treated by surgical resection and the second was cured by application of continuous pressure. The review of the English literature has also been included. An awareness of these vascular injuries, despite their infrequency, is necessary to facilitate early diagnosis, proper investigation and prompt treatment.
Die kerk en sy mag in Openbaring 11
Authors: De Villiers Pieter G.R.
Published: March 2012

The church and power in Revelation 11. The article discusses the notion of power in the episode of the two witnesses in Revelation 11:4–6 as a point of departure for a reflection on power in early Christian documents. It also aims to determine the meaning of power in terms of a close reading of a specific text so that discussions about its nature and about power in Biblical texts can be rooted in firm evidence. This evidence should then, at later stages be further developed with the aid of theoretical models and insights about power. In a first section power in Revelation 11:4−6 is described in terms of the identity and task of the witnesses and in terms of its divine origins, followed in a second part by reflection on the direct references to their power. Special attention is given to some seminal issues about power, namely, its relationship with truth and prophecy, its divine origins, the misuse of power, violence as a response to evil and, finally, its role in the Book of Revelation and Early Christianity.
Does warming enhance the effect of microzooplankton grazing on marine phytoplankton in the ocean?
Authors: Chen Bingzhang , Landry Michael R. , Huang Bangqin , Liu Hongbin
Published: March 2012

We evaluated a hypothesis derived from the metabolic theory of ecology (MTE) that the ratio of microzooplankton herbivory (m) to phytoplankton growth (μ) will arise in a warming ocean because of the different temperature dependencies of autotrophic and heterotrophic organisms. Using community‐level growth and grazing data from dilution experiments, generalized additive models (GAMs) were constructed to describe the effects of temperature and chlorophyll on m : μ. At low chlorophyll levels, m : μ decreases with increasing temperature, whereas at high chlorophyll levels, m : μ increases initially with temperature before reaching a peak and then declines. These complex responses of m : μ result from mixed effects of temperature and chlorophyll on microzooplankton biomass (Bz), biomass‐specific microzooplankton grazing rate (m : Bz), and phytoplankton growth rate (μ). Bz decreases with rising temperature and increases with rising chlorophyll. m : Bz increases with temperature and decreases with chlorophyll. Nutrient‐enriched growth rate of phytoplankton (μn) and μ increase with increasing temperature and chlorophyll. Holding chlorophyll constant, the calculated activation energies of m : Bz and μn are 0.67 ± 0.05 and 0.36 ± 0.05 eV, respectively, both consistent with previous MTE estimates for heterotrophs and autotrophs. Our study indicates that warming may enhance phytoplankton losses to microzooplankton herbivory in eutrophic but not in oligotrophic waters. The GAM analysis also provides important insights into underlying system relationships and reasons why community‐level responses in natural systems may depart from theory based on laboratory data and individual species.
Temperature and photoperiod effects on phytoplankton growing under simulated mixed layer light fluctuations
Authors: Shatwell Tom , Nicklisch Andreas , Köhler Jan
Published: March 2012

We measured specific growth rates of Stephanodiscus minutulus, Nitzschia acicularis (diatoms), and Limnothrix redekei (cyanobacterium) under fluctuating and constant light in semi‐continuous culture at 10°C, 15°C, and 20°C and under photoperiods of 6 h d−1 and 12 h d−1. Fluctuating light regimes simulated regular vertical mixing in lakes with a ratio of euphotic to mixed depth (zeu : zmix) of 1 and 0.5 on a cloudless day. Light fluctuations at zeu : zmix = 1 decreased the growth rates of S. minutulus, N. acicularis, and L. redekei by 18%, 33%, and 29%, respectively, compared to constant light at the same daily light supply. Temperature had no effect on this decrease. Halving zeu : zmix (simulating deep mixing) had the same effect on growth as halving the photoperiod, demonstrating that these factors are cumulative. We introduce a simple empirical factor to adjust growth rates measured under constant light to account for fluctuating light. This factor is independent of temperature and photoperiod, applies over a range of zeu : zmix, and accurately describes present and published growth rates of several species. We show how to account for temporal variability of the light supply at different temperatures and photoperiods when predicting growth rates of phytoplankton.
Transformations of carbon in anoxic marine sediments: Implications from Δ14C and δ13C signatures
Authors: Komada Tomoko , Polly Jonathon A. , Johnson Leah
Published: March 2012

Organic‐rich nearshore sediment was incubated in sealed vessels under sulfate‐reducing conditions to investigate the mechanism of dissolved organic carbon (DOC) production in marine sediments. Concentrations and isotopic signatures (δ13C and Δ14C) of particulate organic carbon (POC), DOC, dissolved inorganic carbon (DIC), and particulate inorganic carbon (PIC) were monitored for 130 d. POC solubilization was largely counterbalanced by respiration, resulting in a net increase in DIC of > 35 mmol L−1. Net accumulation of DOC was relatively muted, yet significant, at ∼ 0.04 mmol L−1. All carbon pools exhibited distinct δ13C and Δ14C signatures prior to the incubation. Once the incubation began, these isotopic values varied with time, reflecting exchanges of isotopically distinct moieties across carbon pools. The 14C‐enriched (modern) component of bulk POC was selectively solubilized into DOC, and the majority of this DOC was rapidly respired to DIC. However, net accumulation of DOC was accompanied by a drop in Δ14C, suggesting that during selective solubilization of the younger component of bulk POC, there was concomitant solubilization of pre‐aged organic matter that subsequently accumulated as DOC. PIC was minor in terms of pool size, but likely played a critical role in determining the δ13C signature of pore‐water DIC through isotope exchange.
A Pilot Study on Usability Analysis of Emergency Department Information System by Nurses
Authors: Shapiro J.S. , Genes N. , Aguilar M.V. , Mohrer D. , Baumlin K. , Belden J.L. , Kim M.S.
Published: March 2012

Objectives: Employing new health information technologies while concurrently providing quality patient care and reducing risk is a major challenge in all health care sectors. In this study, we investigated the usability gaps in the Emergency Department Information System (EDIS) as ten nurses differentiated by two experience levels, namely six expert nurses and four novice nurses, completed two lists of nine scenario-based tasks.

Methods: Standard usability tests using video analysis, including four sets of performance measures, a task completion survey, the system usability scale (SUS), and sub-task analysis were conducted in order to analyze usability gaps between the two nurse groups.

Results: A varying degree of usability gaps were observed between the expert and novice nurse groups, as novice nurses completed the tasks both less efficiently, and expressed less satisfaction with the EDIS. The most interesting finding in this study was the result of ‘percent task success rate,’ the clearest performance measure, with no substantial difference observed between the two nurse groups. Geometric mean values between expert and novice nurse groups for this measure were 60% vs. 62% in scenario 1 and 66% vs. 55% in scenario 2 respectively, while there were some marginal to substantial gaps observed in other performance measures. In addition to performance measures and the SUS, sub-task analysis highlighted navigation pattern differences between users, regardless of experience level.

Conclusion: This study will serve as a baseline study for a future comparative usability evaluation of EDIS in other institutions with similar clinical settings.
Building block method: a bottom-up modular synthesis methodology for distributed compliant mechanisms
Authors: Krishnan G. , Kim C. , Kota S.
Published: March 2012

Abstract. Synthesizing topologies of compliant mechanisms are based on rigid-link kinematic designs or completely automated optimization techniques. These designs yield mechanisms that match the kinematic specifications as a whole, but seldom yield user insight on how each constituent member contributes towards the overall mechanism performance. This paper reviews recent developments in building block based design of compliant mechanisms. A key aspect of such a methodology is formulating a representation of compliance at a (i) single unique point of interest in terms of geometric quantities such as ellipses and vectors, and (ii) relative compliance between distinct input(s) and output(s) in terms of load flow. This geometric representation provides a direct mapping between the mechanism geometry and their behavior, and is used to characterize simple deformable members that form a library of building blocks. The design space spanned by the building block library guides the decomposition of a given problem specification into tractable sub-problems that can be each solved from an entry in the library. The effectiveness of this geometric representation aids user insight in design, and enables discovery of trends and guidelines to obtain practical conceptual designs.
Analyzing the temporal fluctuations of the reservoir-triggered seismicity observed at Açu (Brazil)
Authors: Telesca L. , do Nascimento A. F. , Bezerra F. H. R. , Ferreira J. M.
Published: March 2012

Abstract. The time dynamics of the reservoir-induced seismicity observed in Açu area (Brazil) from November 1994 to April 1997 reveals a super-Poissonian behaviour in the direction of a clustering process, where the occurrence of an earthquake increases the likelihood of the occurrence of a subsequent one. The seismicity shows strong correlation for time scales larger than approximately 1 day up to about four months, being characterized by Poissonian behavior for timescales smaller than 1 day. Processes of formation of fractures in the anisotropic and heterogeneous rockmass, along with pore pressure diffusion driven processes, are hypothesized as physical mechanisms for the appearance of Poissonian and clusterized dynamics respectively.
Reprogramming Approaches for Human Heart Disease
Authors: Srivastava Deepak
Published: March 2012

Heart disease is a leading cause of death in adults and children. We, and others, have described complex signaling, transcriptional and translational networks that guide early differentiation of cardiac progenitors and later morphogenetic events during cardiogenesis. We found that networks of transcription factors and miRNAs function through positive and negative feedback loops to reinforce differentiation and proliferation decisions. Many of the same cues have been leveraged to control differentiation of pluripotent stem cells into cardiac, endothelial and smooth muscle cells that may be useful for regenerative purposes. We have used similar approaches to direct differentiation of disease-specific human induced pluripotent stem cells in order to model human heart disease.

Recently, we utilized a combination of major cardiac regulatory factors, Gata4/Mef2c/Tbx5, to induce direct reprogramming of cardiac fibroblasts into cardiomyocyte-like cells with global gene expression and electrical activity similar to cardiomyocytes. The reprogramming was a stable event at the epigenetic level. We have now used genetic lineage-tracing techniques to demonstrate that resident cardiac fibroblasts can be reprogrammed into induced cardiomyocytes in vivo using a gene therapy approach. The in vivo efficiency of reprogramming into cells that are more fully reprogrammed into beating cardiomyocytes was greater than in vitro and resulted in improved cardiac function after injury. Knowledge regarding the early steps of cardiac differentiation in vivo has led to effective strategies to generate necessary cardiac cell types for disease-modeling and regenerative approaches, and promise to lead to new strategies for human heart disease.
Stem Cell Research: From Promise to Practice
Authors: Al Aqeel Aida
Published: March 2012

Stem cells are unspecialized cells able to divide and produce copies of themselves and having the potential to differentiate, ie to produce other cell types in the body. Because of the latter ability, the scientists investigate their possible use in regenerative medicine. Embryonic stem cells (ESCs), especially, have huge therapeutic potential because they can give rise to every cell type in the body (pluripotency) as compared to stem cells from certain adult tissues that can only differentiate into a limited range of cell types. For this reason scientists stress the importance of embryonic stem cell research. However, this research raises sensitive ethical and religious arguments, which are balanced against possible great benefit of such research for the patients suffering from so far incurable diseases. Serious questions remain about safety.

In Saudi Arabia, for the last five years, the Stem Cell Therapy Program has been established at King Faisal Specialist hospital and research center with the launch of 10 projects. Embryonic stem cell therapy for genetics metabolic disorders is one of the most promising modalities for the therapy and prevention of mentally and physically handicapped in children.

Recent advances in the field of cloning and stem cell research has raised many complex questions. It is rare that a field of science causes debate and challenge not only among scientists, but also among ethicists, religious scholars, governments and politicians. There is no consensus on the morality of human cloning, even within specific religious traditions. In countries in which religion has a strong influence on political decision-making, the moral status of the human embryo is at the center of the debate. We will discuss our experience; how Islamic teachings make this very promising research and therapeutic technique, and modality of treatment permissible; and the Islamic perspectives about reproductive/therapeutic cloning.

In conclusion, it is still unclear which human stem cells— whether embryonic or adult — will be developed and for which conditions. Qualities of the ideal stem cell in a clinical setting are expected to be extensive and far reaching. The ability for stem cells to be expanded in culture without genetic and epigenetic abnormalities, their ability to form functional cell types in vitro and in vivo, and their immuno-compatibility with the patient need to be studied. Given this, the focus of research community should be on developing human research capacity in both ASCs and ESCs. Each type of research will take time to mature. The ethical debate will need to produce acceptable policy and regulatory compromises so that the regulatory burden can be reduced and investors’ risk aversion can be overcome. If these things happen, the major remaining barrier to realizing the medical benefits of stem-cell research might be the lack of skilled scientists in the field. Our experience in Saudi Arabia will be presented.
Overview of Present Guidelines on Stem Cell Research
Authors: Ali Faleh Mohamed Hussein
Published: March 2012

Human stem cells, particularly embryonic stem cells, have unlimited capacity to develop into different types of cells such as muscle cells, nerve cells, heart cells, blood cells and others. Therefore, human stem cells hold the promise of a renewable source of replacement cells and tissues to treat an ever growing list of human diseases and conditions, including Parkinson's disease, amyotrophic lateral sclerosis, spinal cord injury, burns, heart disease, diabetes and arthritis.

On the other hand, stem cell research has led to great controversy. The controversy centers on the ethics of conducting research involving the generation, usage and destruction of human embryonic stem cells. But it should be noted that new approaches and innovative strategies have yielded human stem cells without destruction of embryos via generating pluripotent stem cells from adult cells.

The Supreme Council of Health (SCH) has developed a policy for the ethical use of human stem cells in research. The policy provides guidance and procedures under which proposed research in this area, conducted in Qatar publicly or privately funded, is ethically responsible, scientifically worthy, and conducted in accordance with national and international laws.

The SCH presentation will introduce the research community to what is allowed and not allowed in research involving human embryonic stem cells in Qatar.
Umbilical cord blood transplantation: Saudi Arabia experience
Authors: Al Humaidan Hind
Published: March 2012

Transplantation of allogeneic bone marrow has been successfully used in the treatment of high risk or recurrent hematologic malignancies, bone marrow failure syndromes, selected hereditary immunodeficiency states and metabolic disorders.
Early in the history of bone marrow transplantation, it was clear that access to a suitable donor was a major obstacle severely limiting the use of this potentially curative treatment modality. Although using an HLA sibling donor is the best choice for transplantation, not all patients could have access to such a donor, therefore transplant centers explored the possibility of using volunteer adult unrelated donors as an alternative to HLA–matched siblings. In addition, there was another alternative treatment strategy as a source of hematopoietic stem cell namely Umbilical Cord Blood. In Saudi Arabia, 60 percent of our patients who need a transplant will find an HLA-matched sibling donor, leaving 40 percent of the patients in need of alternative sources. The concept of establishing a Cord Blood Bank in Saudi Arabia under the umbrella of King Faisal Specialist Hospital & Research Centre was raised after the increase in the rate of using cord blood for transplantation due to the inability of finding fully or closely HLA-matched related donors. This Cord Blood Bank is a non-profit public cord blood bank dedicated to making high quality cord blood units available to all patients in need of related and/or unrelated transplantation in the Kingdom of Saudi Arabia and in the neighboring countries through the development and maintenance of a center of excellence for the collection, storage, search and distribution of ethnically and racially diverse cord blood units. Additionally, the mission of the Cord Blood Bank is to educate both the medical community and the public to the value of cord blood donation collection and cryopreservation, and increase the awareness of the importance of cord blood banking. To date, our inventory consists of 3,725 units of high quality cord blood with a total of 70 cord blood transplants carried out from our own inventory.
An international perspective on the regulation of biosamples
Authors: Ellson Sarah
Published: March 2012

This presentation will provide an additional perspective to that of the scientific and ethical issues that surround biosamples, by considering the appropriate role of regulation in this area. A regulatory regime can be used to ensure that the individuals, organisations and activities are governed in such a way as to ensure the highest ethical and scientific standards are maintained. Right touch regulation should promote innovation and should not be overly burdensome, but it is required to ensure that, in the highly sensitive area of biosampling, there is an appropriate framework in which high calibre operators can function and unsafe or unethical practise is prevented. As stem cell and biosample banking expands into new scientific and geographic areas regulation has to be sufficiently flexible to adapt to the unknown. It is also required if the bio banking communities are going to operate internationally.The presentation will consider what the international community might expect to see in regulatory terms as the Middle East expands into these opportunities. Regulation should be understood as key to ensuring confidence in the processes involved in biosampling. The presentation will look at some of the regulatory issues and challenges encountered in Europe and beyond and discuss the perspective and lessons to be learned. Central to the discussion will be consent issues and how consent may be embedded in regulation to underpin approaches to the storage, import and export and research with human tissue and cells.
Generation of red blood cells from pluripotent stem cells as an alternative to donated blood
Authors: Mountford Joanne
Published: March 2012

We are working to generate human red blood cells from human pluripotent stem cells at sufficient levels of quality and safety to warrant entry to pre-clinical and clinical studies. These in vitro generated red blood cells (RBCs) offer an alternative to donated blood and may be of particular use for patients receiving repeated red cell transfusions including those with sickle cell disease and thalassaemias. In order to generate RBCs suitable for clinical use we have derived 10 new clinical grade GMP human embryonic stem cell lines. Our erythroid differentiation protocol is suspension culture based with no co-culture. The protocol, which lasts 24 days, achieves ~20,000 fold expansion in cell numbers and results in ~95% of the cells in culture expressing erythroid markers (glycophorin A, CD71, CD36)and having the characteristic morphology of haemoglobinised normoblasts. HPLC and quantitative PCR analysis of globin chains show that fetal alpha and gamma chains predominate with embryonic epsilon and zeta chains only comprising >5% of total globins. Minimal spontaneous enucleation (≤5%) has observed, however, nucleated erythroid cells examined for their ability to bind and release oxygen (in a Hemox Analyser) demonstrated a similar profile to cord blood derived RBCs, consistent with the presence of fetal haemoglobin in these cells. We are currently testing our differentiation protocol with induced pluripotent stem cells (iPSC) and dissecting the molecular profile of the hESC-derived day 24 normoblast population in order to better understand why these cells do not enucleate as readily as adult haematopoietic stem cell derived erythrocytes. In addition to these remaining biological issues, we are addressing the processes needed for GMP-grade scale up of the protocol to facilitate the production of large numbers of clinically acceptable RBCs.

J. C. Mountford1,4, D. Anstee2, A. Courtney6, L. Forrester4, W. Murphy3, S. Parsons2, P. de Sousa6,5 and M.L Turner1.

Scottish National Blood Transfusion Service1, NHS Blood and Transplant2, Irish Blood Transfusion Service3, University of Glasgow4, University of Edinburgh5 and Roslin Cells Ltd6. United Kingdom.
From Dissertation to Publication in JRME
Authors: Thanheiser Eva , Ellis Amy , Herbel-Eisenmann Beth
Published: March 2012

In this Research Commentary, 3JRMEauthors describe the process of publishing their research inJRME. All 3 authors published parts of their dissertation inJRMEand are sharing their stories to help (new) researchers in mathematics education better understand the process and to offer (experienced) researchers in mathematics education a tool that can be used to mentor their less experienced colleagues and students. The authors address preparing, conceptualizing, and writing a manuscript as well as responding to reviewers.
Seeing With Two Eyes: A Teacher's Use of Gestures in Questioning and Revoicing to Engage English Language Learners in the Repair of Mathematical Errors
Authors: Shein Paichi Pat
Published: March 2012

This revelatory case study examines a 5th-grade teacher's orchestration of discourse and interaction to create opportunities for English language learners to participate in the repair of mathematical errors during a unit on finding the area of geometric shapes. The analysis of discourse takes on a binocular perspective of considering gesture and speech as a unity (McNeill, 1992). The teacher's pointing, representational, and writing gestures were studied in relation to her questioning and revoicing. This research was guided by a social learning theory that characterizes learning as active and interactive participation in communities of practice (Lave & Wenger, 1991; Wenger, 1998). The findings detail how the teacher used gestures in grounding her questioning, revoicing students' strategies, and narrating the meaning of geometric features.
Confirmation of drug delivery after liver chemoembolization: direct tissue doxorubicin measurement by UHPLC‐MS‐MS
Authors: Baumgarten Sigrid , Gaba Ron C. , van Breemen Richard B.
Published: March 2012

Because liver cancer is rarely suitable for surgery, transcatheter arterial chemoembolization (TACE) is used for palliative therapy. In this procedure, an emulsion of doxorubicin in iodized oil is injected directly into liver tumors through a catheter positioned within the artery supplying blood flow to the tumor. At present, there is limited understanding of factors affecting the delivery and dispersion of doxorubicin within treated tumors during TACE. This study addresses the development and application of an ultrahigh‐pressure liquid chromatography–tandem mass spectrometry (UHPLC‐MS‐MS) method for rapid confirmation of drug delivery after TACE in a rabbit VX2 liver cancer model. Doxorubicin levels in liver tumors were measured using UHPLC‐MS‐MS and compared with computed tomography measured levels of iodized oil, a metric used clinically to indicate drug delivery. We found that tissue drug levels determined using UHPLC‐MS‐MS did not correlate with the regional iodized oil concentration (vehicle) within tumors following TACE, suggesting that chemotherapeutic drugs like doxorubicin spread throughout tumors, and that lack of iodized oil staining in portions of a tumor does not necessarily indicate inadequate therapy during TACE. Copyright © 2012 John Wiley & Sons, Ltd.
Nitraminoazoles Based on ANTA – A Comprehensive Study of Structural and Energetic Properties
Authors: Dippold Alexander A. , Klapötke Thomas M. , Martin Franz A. , Wiedbrauk Sandra
Published: March 2012

Since 5‐Amino‐3‐nitro‐1H‐1,2,4‐triazole (ANTA) is known to be a thermally very stable secondary explosive, our goal in this contribution was the synthesis of thermally stable but more powerful energetic compounds based on ANTA. Hence, we utilized ANTA to synthesize 5‐nitramino‐3‐nitro‐1H‐1,2,4‐triazole (1) by nitration with a mixture of concentrated sulfuric acid and 100 % nitric acid. ANTA was also methylated with dimethyl sulfate to yield 5‐amino‐1‐methyl‐3‐nitro‐1,2,4‐triazole (2), which was then subsequently nitrated by using the method mentioned above to yield 1‐methyl‐5‐nitramino‐3‐nitro‐1,2,4‐triazole (3). All three compounds were characterized by IR and Raman as well as multinuclear NMR spectroscopy. Additionally, X‐ray crystallographic measurements of 1 and 3 were performed. The decomposition points of the compounds were found to be low for 1 (135 °C) and 3 (108 °C), despite the high thermal stability of ANTA (>220 °C) and 2 (294 °C). In order to increase the thermal stability of the compounds, nitrogen‐rich salts of 1 and 3 with the ammonium, hydrazinium, guanidinium, aminoguanidinium, and triaminoguanidinium cations were prepared and fully characterized by means of vibrational and NMR spectroscopy, DSC measurements, and X‐ray diffraction measurements. Additionally, the impact as well as friction sensitivities and the sensitivity against electrostatic discharge were determined by using standard BAM techniques. The standard heats of formation were calculated for selected compounds at the CBS‐4M level of theory, which reveals high positive heats of formation for all compounds.
Holding back the microfilament—Structural insights into actin and the actin‐monomer‐binding proteins of apicomplexan parasites
Authors: Olshina Maya A. , Wong Wilson , Baum Jake
Published: March 2012

Parasites from the phylum Apicomplexa are responsible for several major diseases of man, including malaria and toxoplasmosis. These highly motile protozoa use a conserved actomyosin‐based mode of movement to power tissue traversal and host cell invasion. The mode termed as ‘gliding motility’ relies on the dynamic turnover of actin, whose polymerisation state is controlled by a markedly limited number of identifiable regulators when compared with other eukaryotic cells. Recent studies of apicomplexan actin regulator structure—in particular those of the core triad of monomer‐binding proteins, actin‐depolymerising factor/cofilin, cyclase‐associated protein/Srv2, and profilin—have provided new insights into possible mechanisms of actin regulation in parasite cells, highlighting divergent structural features and functions to regulators from other cellular systems. Furthermore, the unusual nature of apicomplexan actin itself is increasingly coming into the spotlight. Here, we review recent advances in understanding of the structure and function of actin and its regulators in apicomplexan parasites. In particular we explore the paradox between there being an abundance of unpolymerised actin, its having a seemingly increased potential to form filaments relative to vertebrate actin, and the apparent lack of visible, stable filaments in parasite cells. 2012 IUBMB IUBMB Life, 2012
Supramolecular Synthesis of Graphenic Mesogenic Materials
Authors: Guo Fei , Hurt Robert
Published: March 2012

Supramolecular chemistry offers new routes for creation of carbon and graphene‐based materials with precise control of structure. This approach stacks, aligns, polymerizes, or otherwise directs the assembly of precursor molecules into non‐covalent superstructures or macromolecular intermediates that are then chemically converted to carbon. A subset of this field uses liquid crystal phases, or mesophases, which exhibit orientational molecular order somewhere along the chemical trajectory to carbon. Covalent capture of that orientational order followed by heteroatom removal leads to “mesogenic graphenic materials”. This review article addresses these carbons and focuses on new methods and materials that use well‐defined molecular precursors. It discusses polyaromatic compounds as starting materials, assembly modes in the melt and solvent phases, and potential applications.