bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the Extent of Impervious Surfaces and Turf Grass across Large Regions
Authors: Claggett Peter R. , Irani Frederick M. , Thompson Renee L.
Published: September 2013

The ability of researchers to accurately assess the extent of impervious and pervious developed surfaces, e.g., turf grass, using land‐cover data derived from Landsat satellite imagery in the Chesapeake Bay watershed is limited due to the resolution of the data and systematic discrepancies between developed land‐cover classes, surface mines, forests, and farmlands. Estimates of impervious surface and turf grass area in the Mid‐Atlantic, United States that were based on 2006 Landsat‐derived land‐cover data were substantially lower than estimates based on more authoritative and independent sources. New estimates of impervious surfaces and turf grass area derived using land‐cover data combined with ancillary information on roads, housing units, surface mines, and sampled estimates of road width and residential impervious area were up to 57 and 45% higher than estimates based strictly on land‐cover data. These new estimates closely approximate estimates derived from authoritative and independent sources in developed counties.
Total Maximum Daily Load Criteria Assessment Using Monitoring and Modeling Data
Authors: Keisman Jeni , Shenk Gary
Published: September 2013

Applications of Total Maximum Daily Load (TMDL) criteria for complex estuarine systems like Chesapeake Bay have been limited by difficulties in estimating precisely how changes in input loads will impact ambient water quality. A method to deal with this limitation combines the strengths of the Chesapeake Bay's Water Quality Sediment Transport Model (WQSTM), which simulates load response, and the Chesapeake Bay Program's robust historical monitoring dataset. The method uses linear regression to apply simulated relative load responses to historical observations of water quality at a given location and time. Steps to optimize the application of regression analysis were to: (1) determine the best temporal and spatial scale for applying the WQSTM scenarios, (2) determine whether the WQSTM method remained valid with significant perturbation from calibration conditions, and (3) evaluate the need for log transformation of both dissolved oxygen (DO) and chlorophyll a (CHL) datasets. The final method used simple linear regression at the single month, single WQSTM grid cell scale to quantify changes in DO and CHL resulting from simulated load reduction scenarios. The resulting linear equations were applied to historical monitoring data to produce a set of “scenario‐modified” DO or CHL concentration estimates. The utility of the regression method was validated by its ability to estimate progressively increasing attainment in support of the 2010 Chesapeake Bay TMDL.
Fold or hold: experimental evolution in vitro
Authors: Collins S. , Rambaut A. , Bridgett S. J.
Published: September 2013

We introduce a system for experimental evolution consisting of populations of short oligonucleotides (Oli populations) evolving in a modified quantitative polymerase chain reaction (qPCR). It is tractable at the genetic, genomic, phenotypic and fitness levels. The Oli system uses DNA hairpins designed to form structures that self‐prime under defined conditions. Selection acts on the phenotype of self‐priming, after which differences in fitness are amplified and quantified using qPCR. We outline the methodological and bioinformatics tools for the Oli system here and demonstrate that it can be used as a conventional experimental evolution model system by test‐driving it in an experiment investigating adaptive evolution under different rates of environmental change.
Inhibition of matrix metalloproteinase‐9 and nuclear factor kappa B contribute to melatonin prevention of motility and invasiveness in HepG2 liver cancer cells
Authors: Ordoñez Raquel , Carbajo‐Pescador Sara , Prieto‐Dominguez Néstor , García‐Palomo Andrés , González‐Gallego Javier , Mauriz José L.
Published: September 2013

Hepatocellular carcinoma (HCC) is one of the most lethal human cancers worldwide because of its high incidence and its metastatic potential. Extracellular matrix degradation by matrix metalloproteinases (MMPs) has been connected with cancer cell invasion, and it has been suggested that inhibition of MMPs by synthetic and natural inhibitors may be of great importance in the HCC therapies. Melatonin, the main product of the pineal gland, exerts antiproliferative, proapoptotic, and antiangiogenic properties in HepG2 human hepatocellular cells, and exhibits anti‐invasive and antimetastatic activities by suppressing the enzymatic activity of MMP‐9 in different tumor types. However, the underlying mechanism of anti‐invasive activity in HCC models has not been fully elucidated. Here, we demonstrate that 1 mm melatonin dosage reduced in IL‐1β‐induced HepG2 cells MMP‐9 gelatinase activity and inhibited cell invasion and motility through downregulation of MMP‐9 gene expression and upregulation of the MMP‐9‐specific inhibitor tissue inhibitor of metalloproteinases (TIMP)‐1. No significant changes were observed in the expression and activity of MMP‐2, the other proteinase implicated in matrix collagen degradation, and its tissue inhibitor, TIMP‐2. Also, melatonin significantly suppressed IL‐1β‐induced nuclear factor‐kappaB (NF‐κB) translocation and transcriptional activity. In summary, we demonstrate that melatonin modulates motility and invasiveness of HepG2 cell in vitro through a molecular mechanism that involves TIMP‐1 upregulation and attenuation of MMP‐9 expression and activity via NF‐κB signal pathway inhibition.
The Impact of Front‐End Innovation Activities on Product Performance
Authors: Markham Stephen K.
Published: September 2013

This paper describes and tests a model of the impact of front‐end innovation activities on product performance. Data were collected from 272 companies to test the hypothesis that front‐end performance impacts new product performance in the marketplace while controlling for new product development (NPD) processes and strategy. The data support the hypothesis that front‐end performance favorably and independently impacts overall product success, time to market, market penetration, and financial performance.

Front‐end performance is predicted by a set of activities, including: the actual amount of front‐end work done in various areas, specifically marketing, R&D, and concept development; the existence of a front‐end process; the existence of a champion; and agreement on the order of developmental steps in the front end. Front‐end activities are related to front‐end performance, and front‐end performance is related to NPD performance. This relationship highlights the distinction between front‐end activities and standard product development practices and the importance of building competency in the front end.

This is the first study that quantifies both the nature and amount of work done in the front end and relates that work to commercial performance. This research empirically demonstrates the distinction between the front‐end and formal stages and gates types of systems. This suggests that the concept of the front end needs it own set of theoretical constructs to adequately describe and predict this categorically different set of activities. While this study demonstrates the difference between front‐end and stage‐gate systems, it does not establish the limits of those activities.

From a managerial point of view recognizing that formal development and front‐end activities are different mandates that these activities must be managed differently. In particular, the skills, structures, processes, governance, leadership, performance metrics, and resources must be assessed separately and differently. These findings suggest that firms should actively manage the flow of ideas from the front end into the more formal development programs.
Character Strengths and Deep Connections Following Hurricanes Katrina and Rita: Spiritual and Secular Pathways to Resistance Among Volunteers
Authors: Ai Amy L. , Richardson Roslyn , Plummer Carol , Ellison Christopher G. , Lemieux Catherine , Tice Terrence N. , Huang Bu
Published: September 2013

This study investigated a conceptual model with two pathways, altruism and perceived spiritual support, leading to resilience among student volunteers following Hurricanes Katrina and Rita (H‐KR). Both strengths share the sense of deep connections. Parallel pathways with the two major constructs were estimated using structural equation modeling, adjusting for demographics and peritraumatic emotional reactions. The two indicators may have served as a protective mechanism for all volunteers despite differing racial/cultural backgrounds. The potential protection of these strength factors was mediated through optimism and hope. Resilience among minority volunteers was associated more with faith‐related strengths, as indicated in the relevant pathway that also contributed to their altruistic actions. The resilience of white volunteers, however, was directly associated with altruism, a strength that does depend heavily on religious beliefs. Further, the modification index suggested a direct path from race to depression.
Are Muslims a Distinctive Minority? An Empirical Analysis of Religiosity, Social Attitudes, and Islam
Authors: Lewis Valerie A. , Kashyap Ridhi
Published: September 2013

Scholarly and public discourses on Muslim immigrants in Europe have questioned if Islam is an impediment to sociocultural adaptation and whether Muslims are a distinctive group in their religiosity and social values. We use a new survey of 480 British Muslims in conjunction with the British Social Attitudes Survey to examine differences between Muslim and non‐Muslim Britons on religiosity (practice, belief, salience) and moral and social issues regarding gender, abortion, and homosexuality. Muslims are more religious than other Britons, including both British Christians and religious “nones.” Muslims also are more conservative than other Britons across the range of social and moral attitudes. Multivariate analysis shows, however, that much of the difference on moral issues is due to socioeconomic disadvantage and high religiosity among Muslims. Although being a highly religious group in an otherwise secular country renders Muslims distinctive, factors that predict social conservatism among all Britons—high religiosity and low SES—apply similarly to Muslims.
Examining Trends in Muslim Self‐Identification and Mosque Attendance Among People of Turkish and Moroccan Descent in the Netherlands, 1997–2009
Authors: Smits Fransje , Ultee Wout
Published: September 2013

This study examines the extent to which Muslim self‐identification and mosque attendance have changed in the period 1997–2009 among people of Turkish and Moroccan descent in the Netherlands. Mainly trendless fluctuations are found. Overall, Muslim self‐identification seems to very slightly increase and mosque attendance seems to very slightly decrease. We examined the extent to which factors that are important according to theories and previous research explain or enlarge these differences over time. The factors about which we hypothesize are largely unable to explain differences over time in Muslim self‐identification and mosque attendance.
Outsourcing Moral Authority: The Internal Secularization of Evangelicals’ Anti‐Pornography Narratives
Authors: Thomas Jeremy N.
Published: September 2013

Based on content analysis of the popular evangelical magazineChristianity Today, I show that while evangelicals' outward opposition to pornography has remained steady and robust across the period 1956 to 2010, nonetheless, during this same time, evangelicals' anti‐pornography narratives have become increasingly secular. Through using and expanding Chaves's notion of internal secularization, I demonstrate how these narratives have become decreasingly legitimated through religious forms of moral authority such as scriptural prohibitions and derivative ideas about God's plan for society, and increasingly legitimated through secular forms of moral authority such as humanistic conceptions of individual rights and of psychological health. I refer to this type of internal secularization as the process of outsourcing moral authority, and I discuss the theoretical significance of this process for potential investigations of a range of other moral narratives.
Hydrogeochemistry of the Catskill Mountains of New York
Authors: Parisio Steven J. , Halton Casey R. , Bowles Emily K. , Keimowitz Alison R. , Corey Karen , Myers Kellie , Adams Morton S.
Published: September 2013

Major ion chemistry of Catskill region groundwater is characterized on the basis of 207 analyses compiled from three sources, including a web‐based U.S. Geological Survey database, state agency regulatory compliance data, and sampling of trailside springs performed by the authors. All samples were analyzed for the complete set of major ions, including calcium, magnesium, sodium, potassium, bicarbonate, chloride, sulfate, and nitrate. Groundwater in pristine, high‐elevation areas of the Catskill Peaks was found to be predominantly of calcium bicarbonate, calcium sulfate, or calcium bicarbonate–sulfate types, with relatively low ionic strength. Groundwater at lower elevations along the margins of the region or in valley bottoms was predominantly of sodium–chloride or sodium–bicarbonate types, showing the effects of road salt and other local pollution sources. Nitrate and sulfate enrichment attributable to regional air pollution sources were most evident in the high‐elevation spring samples, owing to the generally low concentrations of other major ions. Trailside springs appear to be viable low‐cost sources for obtaining samples representative of groundwater, especially in remote and inaccessible areas of the Catskill forest preserve.
Failure of Intralesional Propranolol in Infantile Hemangiomas
Authors: Torres‐Pradilla Mauricio , Baselga Eulalia
Published: September 2013

The purpose of this study was to evaluate the use of intralesional propranolol injection in the management of small, noncomplicated infantile hemangiomas (IHs) located in areas of cosmetic concern. A prospective study was performed in six female infants with small, non‐complicated IHs in areas of cosmetic concern. The parents had refused oral propranolol or the patients had no response to topical timolol or had relapsed after oral propranolol and the parents refused further systemic treatment. All six patients were treated with 1 mg/mL propranolol solution at a dose of 0.2 mL/cm2. The size, color, and growth of the hemangiomas were monitored and recorded every 4 weeks. Treatment response was evaluated using a 5‐point scale: much better (+2), better (+1), same (0), worse (−1), and much worse (−2). Heart rate and blood pressure were measured before and 1 hour after each injection. Adverse effects after medication were evaluated and managed accordingly. All hemangiomas stopped growing during therapy, but no significant changes in size or color were observed, even after repeated injections, and all patients were evaluated as 0 (same). One patient whose hemangioma stopped growing during treatment presented rebound growth after therapy cessation. No changes in heart rate or blood pressure were observed after intralesional propranolol injection. Adverse effects observed were pain and redness after injection. Intralesional propranolol seems safe but is not effective for the treatment of IH.
Brain tumor response to nimotuzumab treatment evaluated on magnetic resonance imaging
Authors: Dalmau Evelio Rafael González , Cabal Mirabal Carlos , Martínez Giselle Saurez , Dávila Agustín Lage , Suárez José Carlos Ugarte , Cabanas Armada Ricardo , Rodriguez Cruz Gretel , Darias Zayas Daniel , Castillo Martha Ríos , Valle Garrido Luis , Sotolongo Luis Quevedo , Fernández Mercedes Monzón
Published: September 2013

Background

Nimotuzumab, a humanized monoclonal antibody anti‐epidermal growth factor receptor, has been shown to improve survival and quality of life in patients with pediatric malignant brain tumor. It is necessary, however, to increase the objective response criteria to define the optimal therapeutic schedule. The aim of this study was to obtain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) quantitative information related to dimensions and morphology, molecular mobility and metabolic activity of the lesion and surroundings in order to evaluate any changes through time.

Methods

Fourteen pediatric patients treated with nimotuzumab were evaluated on MRI and MRS for >2 years. Each patient was their own control. The MRI/MRS pulse sequence parameters were standardized to ensure experimental reproducibility.

Results

A total of 71.4% of patients had stable disease; 21.4% had objective response and 7.1% had progression of disease during the >2 year evaluation period.

Conclusions

MRI/MRS data with clinical information provide a clearer picture of treatment response and confirm once again that nimotuzumab is effective in the treatment of pediatric brain tumor. These imaging procedures can be a useful tool for the clinical evaluation of study protocol in clinical practice.
Translation and validation of the Children's Communication Checklist to evaluate pragmatic language impairment in Thai children
Authors: Chuthapisith Jariya , Taycharpipranai Pasinee , Roongpraiwan Rawiwan , Ruangdaraganon Nichara
Published: September 2013

Background

The Children's Communication Checklist (CCC) was developed to provide an assessment of domains of language impairment in children, particularly the pragmatic domain. This study examined the effectiveness of the CCC‐Thai version in discriminating children with autism spectrum disorders (ASD) from typically developing children.

Methods

The parents of two groups of 50 children aged 4–6 years, one with clinically ascertained ASD, and one with typical development, completed the CCC‐Thai version.

Results

The mean pragmatic composite score was significantly lower in the ASD group (124.6) than in the typical development group (142). The optimal receiver operating characteristic curve cut‐off score was found to be identical to the original English version (132). Corresponding sensitivity and specificity were 94% and 86%, respectively. The positive predictive value and the negative predictive value were 87% and 93%, respectively. The corresponding area under the curve was 0.95 (95% confidence interval: 0.91–0.99).

Conclusion

The CCC‐Thai version is a promising instrument to assess pragmatic language impairment in Thai children.
Chemical Analysis of the Luminous Slime Secreted by the Marine Worm Chaetopterus (Annelida, Polychaeta)
Authors: Branchini Bruce R. , Behney Curran E. , Southworth Tara L. , Rawat Renu , Deheyn Dimitri D.
Published: September 2013

The marine annelid Chaetopterus variopedatus produces bioluminescence by an unknown and potentially novel mechanism. We have advanced the study of this fascinating phenomenon, which has not been investigated for nearly 60 years after initial studies were first reported for this species. Here, we show that the luminous slime produced by the worm exhibits blue fluorescence that matches the bioluminescence emission. This result suggests that the oxyluciferin emitter is present. However, while the blue fluorescence decays over time green fluorescence is increasingly revealed that is likely associated with products of the luminescence reaction. LC/MS and fluorescence analysis of harvested luminescent material revealed riboflavin as the major green fluorescent component. Riboflavin is usually associated with the mechanism of light production in bacteria, yet luminous bacteria were not found in the worm mucus, and accordingly were not reported to be directly responsible for the light emission, which is under nervous control in the worm. We therefore propose a hypothesis in which riboflavin or a structurally related derivative serves as the emitter in the worm's light producing reaction.
Catechol‐O‐methyltransferase activity in psoriasis patients treated with psoralen plus ultraviolet A therapy
Authors: Souteiro Pedro , Vieira‐Coelho Maria Augusta , Serrão Maria Paula , Magina Sofia
Published: September 2013

Background

Catechol‐O‐methyltransferase (COMT) activity is increased in patients with mild/moderate psoriasis. Narrowband ultraviolet B (nbUVB) phototherapy decreases COMT activity. However, the effect of psoralen plus ultraviolet A (PUVA) on this enzyme activity is unknown, and it remains to be clarified if the nbUVB‐induced effect in COMT activity is related to clinical response. The aim of this study is to evaluate COMT activity in moderate/severe psoriasis and assess whether PUVA therapy modifies this activity.

Methods

An observational study was conducted on 18 patients with moderate/severe psoriasis and 13 matched controls. Patients were treated with PUVA twice weekly during 6 weeks, and they were evaluated for Psoriasis Area and Severity Index (PASI) and COMT activity before photochemotherapy, at the end of it and 4 weeks after stopping.

Results

Before PUVA therapy, S(soluble)‐COMT activity was significantly (P < 0.05) higher in psoriasis patients than in controls. After photochemotherapy, no significant differences were found in S‐COMT activity at all end points. Photochemotherapy significantly decreased PASI but COMT activity values remained higher than those of control population.

Conclusion

Psoriasis patients with moderate/severe disease present higher S‐COMT activity than controls. Although a good clinical response was observed, PUVA therapy does not change S‐COMT activity. This differential COMT effect of PUVA and nbUVB suggests a wavelength‐specific regulation.
Nutritional composition of potential zooplankton prey of spiny lobster larvae: a review
Authors: Wang Miao , Jeffs Andrew G.
Published: September 2013

Spiny lobsters are one of the most valuable seafood products in the world. A major bottleneck to the development of commercial spiny lobster aquaculture is a lack of understanding of the natural diet and nutritional requirements of the larvae. Recent studies have identified the varied pelagic zooplankton prey of spiny lobster phyllosoma, which includes gelatinous taxa, such as ctenophores, jellyfish, salps, chaetognaths, polychaetes, siphonophores and radiolarians, as well as crustaceans, such as amphipods, copepods and krill. In light of these studies, the extensive range of published studies on the biochemical composition of zooplankton have been reviewed in an attempt to provide an initial indication of the possible nutritional requirements of spiny lobster phyllosoma, including protein, lipid, carbohydrate, ash and moisture content. The results indicate that protein is the predominant component in all taxonomic groups of potential prey, which is 46.7 ± 6.0% of dry mass (mean ± SE) in crustaceans and 18.3 ± 7.8% of dry mass in gelatinous zooplankton, followed by lipid, which is 23.8 ± 4.5% of dry mass in crustaceans and 5.3 ± 1.4% of dry mass in gelatinous zooplankton. Carbohydrate is 1.9 ± 0.1% of dry mass in crustaceans and 0.9 ± 0.1% of dry mass in gelatinous zooplankton. Despite the much lower nutrient and energy content of gelatinous zooplankton compared with crustaceans, feeding by phyllosoma on gelatinous zooplankton may provide them more readily accessible nutrients. The results indicate that spiny lobster phyllosoma have a high dietary requirement for protein.
Corpus Luteum Development and Function after Supplementation of Long‐Acting Progesterone During the Early Luteal Phase in Beef Cattle
Authors: Pugliesi G , Oliveria ML , Scolari SC , Lopes E , Pinaffi FV , Miagawa BT , Paiva YN , Maio JRG , Nogueira GP , Binelli M
Published: September 2013

Contents

Strategic supplementation of P4 may be used to increase conception rates in cattle, but timing of supplementation in relation to ovulation, mass of supplementary P4 and formulation of the P4‐containing supplement has not been determined for beef cattle. Effects of supplementation of long‐acting progesterone (P4) on Days 2 or 3 post‐ovulation on development, function and regression of corpus luteum (CL) were studied in beef cattle. Cows were synchronized with an oestradiol/P4‐based protocol and treated with 150 or 300 mg of long‐acting P4 on Day 2 or 3 post‐ovulation (6–7 cows/group). Colour‐doppler ultrasound scanning and blood sample collection were performed from Day 2–21.5. Plasma P4 concentrations were greater (p < 0.05) from Day 2.5–5.5 in the Day 2‐treated groups and from Day 3.5–5.5 in the Day 3‐treated cows than in the control group. CL area and blood flow during Day 2–8.5 did not differ (p > 0.05) among groups, suggesting no effect of P4 treatment on luteal development. The frequency of cows that began luteolysis before Day 15 was greater (p < 0.04) in cows treated with 300 mg than in the controls, but there were no differences between non‐treated and 150 mg‐treated cows. The interval from pre‐treatment ovulation to functional and structural luteolysis was shorter (p < 0.01) in the combined P4‐treated groups than in the control cows. In conclusion, was showed for the first time that long‐acting P4 supplementation on Day 2 or 3 post‐ovulation increases P4 concentrations for ≥3 day, has no effect on luteal development, but anticipates the beginning of luteolysis in beef cattle.
Analytic Philosophy and Christian Theology
Authors: McMartin Jason
Published: September 2013

In the 20th century, a particularly acrimonious relationship took place between analytic philosophy on the one side and Christian theology on the other. Analytic philosophy has been the dominant mode of philosophical engagement in the English‐speaking world. After a long period of hostility or apathy toward religion, it has surged back to the investigation of religious, theological, ethical, and metaphysical questions. The end of the 20th century and the beginning of the 21st century witnessed the explosion of Christian analytic philosophical theology and its exploration of standard doctrines of the Christian faith. I survey the history and nature of analytic philosophy and explore arguments from Christian theology against analytic philosophy to unearth sources of the division between the two. Several positive appropriations of analytic thought are discussed, including analytic philosophy of religion and philosophical theology, postliberalism, process theology, speech–act theory, and proper functionalism. Finally, I briefly propose a mode of future engagement between the two disciplines and will consider the program of analytic theology.
“The Cure of Souls is the Art of Arts:” Preaching, Confession, and Catechesis in the Middle Ages
Authors: Reeves Andrew
Published: September 2013

In the European Middle Ages, the area in which the majority of lay Christians came into contact with the so‐called institutional Church was pastoral care. Three principle areas of this care were preaching, confession, and catechesis. All three provide a window into popular religious practice, and thus, the study of pastoral care benefitted from the social‐historical turn of the 1960s and 1970s and an increased emphasis on “the people.” One of the key aspects of this study of pastoral care has been in investigation of pastoralia, those works of literature meant to help clergy with the cure of souls carry out their tasks. The study of pastoralia begins with the manuscripts, but then aids several different approaches: history of sexuality, feminism, social and cultural history, and history of universities all make abundant use of pastoral literature.
Conservation of fruit dehiscence pathways between Lepidium campestre and Arabidopsis thaliana sheds light on the regulation of INDEHISCENT
Authors: Lenser Teresa , Theißen Günter
Published: September 2013

The mode of fruit opening is an important agronomic and evolutionary trait that has been studied intensively in the major plant model system Arabidopsis thaliana. Because fruit morphology is highly variable between species, and is also often the target of artificial selection during breeding, it is interesting to investigate whether a change in fruit morphology may alter the developmental pathway leading to fruit opening. Here we have studied fruit development in Lepidium campestre, a Brassicaceae species that forms silicles instead of siliques. Transgenic L. campestre plants with altered expression levels of orthologs of A. thaliana fruit developmental genes (ALCATRAZ, FRUITFULL, INDEHISCENT and SHATTERPROOF1,2) were found to be defective in fruit dehiscence, and anatomical sections revealed similar changes in tissue patterning as found in respective A. thaliana mutants. Gene expression analyses demonstrated a high degree of conservation in gene regulatory circuits, indicating that, despite great differences in fruit morphology, the process of fruit opening remains basically unchanged between species. Interestingly, our data identify ALCATRAZ as a negative regulator of INDEHISCENT in L. campestre. By mutant analysis, we found the same regulatory relationship in A. thaliana also, thereby shedding new light on how ALCATRAZ drives separation layer formation.
Contrasting calcium localization and speciation in leaves of the Medicago truncatula mutant cod5 analyzed via synchrotron X–ray techniques
Authors: Punshon Tracy , Tappero Ryan , Ricachenevsky Felipe K. , Hirschi Kendal , Nakata Paul A.
Published: September 2013

Oxalate‐producing plants accumulate calcium oxalate crystals (CaOx(c)) in the range of 3–80% w/w of their dry weight, reducing calcium (Ca) bioavailability. The calcium oxalate deficient 5 (cod5) mutant of Medicago truncatula has been previously shown to contain similar Ca concentrations to wild‐type (WT) plants, but lower oxalate and CaOx(c) concentrations. We imaged the Ca distribution in WT and cod5 leaflets via synchrotron X–ray fluorescence mapping (SXRF). We observed a difference in the Ca distribution between cod5 and WT leaflets, manifested as an abundance of Ca in the interveinal areas and a lack of Ca along the secondary veins in cod5, i.e. the opposite of what is observed in WT. X–ray microdiffraction (μXRD) of M. truncatula leaves confirmed that crystalline CaOx(c) (whewellite; CaC2O4·H2O) was present in the WT only, in cells sheathing the secondary veins. Together with μXRD, microbeam Ca K–edge X–ray absorption near‐edge structure spectroscopy (μXANES) indicated that, among the forms of CaOx, i.e. crystalline or amorphous, only amorphous CaOx was present in cod5. These results demonstrate that deletion of COD5 changes both Ca localization and the form of CaOx within leaflets.
Phosphorylation and growth inhibitory activity of all ketohexose analogs
Authors: Kato‐Noguchi Hisashi , Okada Kozue
Published: September 2013

Sugars are not only important energy sources and structural components, but they also act as signaling molecules that are involved in specific signal sensing. Among all ketohexose analogs (d‐fructose, d‐psicose, d‐tagatose, d‐sorbose, l‐fructose, l‐psicose, l‐tagatose and l‐sorbose), only d‐psicose inhibited the growth of Arabidopsis roots. Phosphorylation by fructokinase occurred in d‐fructose and d‐psicose. d‐Psicose‐induced inhibition was relieved by adding d‐fructose. Thus, the inhibition could not be attributed to the toxicity of phosphorylated d‐psicose. The phosphorylation process requires ATP. After phosphorylation, d‐fructose is metabolized in glycolysis and becomes energy sources and structural components, whereas d‐psicose cannot contribute to the energy sources and structural components because it does not get metabolized further. However, d‐psicose did not affect ATP level in the Arabidopsis roots, suggesting that the d‐psicose‐induced growth inhibition may not be related to the starvation of ATP. The phosphorylation of ketohexoses by fructokinase is known to a trigger signal‐sensing resulting in growth inhibition. Therefore, d‐psicose can be phosphorylated by fructokinase and this process may play a possible role in signal‐sensing. This is probably one of the useful model systems for the study of the hexokinase‐independent sugar‐sensing function and for developing new types of weed‐control agents.
Influence of Model Geometry and Boundary Conditions on the Ultimate Strength of Stiffened Panels Under Uniaxial Compressive Loading
Authors: Xu Ming Cai , Fujikubo Masahiko , Guedes Soares C.
Published: September 2013

The aim of this paper is to determine an appropriate configuration of the boundary conditions and geometric model to calculate the ultimate strength of a continuous stiffened panel under compressive loading in the finite element (FE) analysis. The 1 + 1 spans model with periodical symmetric boundary conditions is proposed to be used in the FE analysis, whose results are compared with the 1/2 + 1 + 1/2 span model with periodical symmetric and symmetric boundary condition, and the 1/2 + 1 + 1 + 1/2 span model with symmetric boundary conditions. The effects of the continuity of the stiffened panel with different geometric models and boundary conditions on its collapse mode are investigated. A beam tension test has been used to define the true stress-strain relationship in the FE analysis. The two-span model, either 1 + 1 or 1/2 + 1 + 1/2, with periodical symmetric conditions give a reasonable FE modeling, which can consider both odd and even number half waves and, thus, have the smallest model uncertainty.
Effects of Joint Discontinuity on the Vibration Power Flow Propagation in a Submerged Cylindrical Shell
Authors: Wang Yun , Zheng Gangtie
Published: September 2013

The propagation characteristics of the vibration power flow in a submerged cylindrical shell with joint discontinuity are investigated by the wave propagation approach. The motion of the cylindrical shell and the pressure field in fluid are described by the Flügge shell theory and the Helmholtz equation, respectively. And the dynamic equations of the system are obtained by the coupling between the shell and the fluid. Then, an analysis of the vibration power flow transmission and reflection at the joint discontinuity is presented and the power flow transmission ratio Tr through the joint discontinuity is studied. Results show that the joint discontinuity can reduce the mean value of the Tr and thus, reduce the energy level of the transmitted vibration, as it has the effect of partially reflecting some of the incident wave with relations to its physical and geometric parameters. The influences of the fluid and the material damping of the joint discontinuity are also studied.
‘Any dead bodies we can exhume?’ Story-Blood and the Politics of Cultural Appropriation in Paula Morris’s Queen of Beauty, Hibiscus Coast, and ‘Rangatira’
Authors: Pistacchi Ann Katherine
Published: September 2013

Taking into account the complicated history surrounding issues of indigenous oral-story appropriation, this paper examines the ways in which appropriation disputes in Aotearoa/New Zealand are played out within Paula Morris’s fictional narratives. Adopting as its base assumption social anthropologist Arnd Schneider’s definition of ‘cultural appropriation’ as ‘taking – from a culture that is not one’s own’ (2003:218), and Jonathan Hart’s belief that cultural appropriation ‘occurs when a member of one culture takes a cultural practice or theory of a member of another culture as if it were his or her own right’ (1997:138), this study uncovers the ways in which Morris’s Maori characters identify and challenge, and at the same time are often complicit with, instances of Pakeha appropriation of indigenous stories, lands, and cultural artifacts.
Antibody-Based Delivery of Interleukin-2 to Neovasculature Has Potent Activity Against Acute Myeloid Leukemia
Authors: Gutbrodt Katrin L. , Schliemann Christoph , Giovannoni Leonardo , Frey Katharina , Pabst Thomas , Klapper Wolfram , Berdel Wolfgang E. , Neri Dario
Published: September 2013

Neovascular structures in acute myeloid leukemia can be targeted using a cognate antibody fused to human interleukin-2.
Surprisingly Easy to Swallow
Authors: Mack William J.
Published: September 2013

A straightforward dysphagia-screening initiative led to an increase in patients tested and a decrease in hospital-acquired pneumonia in the setting of acute stroke.
Pharmacokinetic and Pharmacodynamic Considerations in Antimalarial Dose Optimization
Authors: White Nicholas J.
Published: September 2013

Antimalarial drugs have usually been first deployed in areas of malaria endemicity at doses which were too low, particularly for high-risk groups such as young children and pregnant women. This may accelerate the emergence and spread of resistance, thereby shortening the useful life of the drug, but it is an inevitable consequence of the current imprecise method of dose finding. An alternative approach to dose finding is suggested in which phase 2 studies concentrate initially on pharmacokinetic-pharmacodynamic (PK-PD) characterization and
in vivo
calibration of
in vitro
susceptibility information. PD assessment is facilitated in malaria because serial parasite densities are readily assessed by microscopy, and at low densities by quantitative PCR, so that initial therapeutic responses can be quantitated accurately. If the
in vivo
MIC could be characterized early in phase 2 studies, it would provide a sound basis for the choice of dose in all target populations in subsequent combination treatments. Population PK assessments in phase 2b and phase 3 studies which characterize PK differences between different age groups, clinical disease states, and human populations can then be combined with the PK-PD observations to provide a sound evidence base for dose recommendations in different target groups.
Association of Higher Plasma Vitamin D Binding Protein and Lower Free Calcitriol Levels with Tenofovir Disoproxil Fumarate Use and Plasma and Intracellular Tenofovir Pharmacokinetics: Cause of a Functional Vitamin D Deficiency?
Authors: Havens Peter L. , Kiser Jennifer J. , Stephensen Charles B. , Hazra Rohan , Flynn Patricia M. , Wilson Craig M. , Rutledge Brandy , Bethel James , Pan Cynthia G. , Woodhouse Leslie R. , Van Loan Marta D. , Liu Nancy , Lujan-Zilbermann Jorge , Baker Alyne , Kapogiannis Bill G. , Gordon Catherine M. , Mulligan Kathleen
Published: September 2013

Tenofovir disoproxil fumarate (TDF) causes bone, endocrine, and renal changes by an unknown mechanism(s). Data are limited on tenofovir pharmacokinetics and these effects. Using baseline data from a multicenter study of HIV-infected youth on stable treatment with regimens containing TDF (n= 118) or lacking TDF (n= 85), we measured cross-sectional associations of TDF use with markers of renal function, vitamin D-calcium-parathyroid hormone balance, phosphate metabolism (tubular reabsorption of phosphate and fibroblast growth factor 23 [FGF23]), and bone turnover. Pharmacokinetic-pharmacodynamic associations with plasma tenofovir and intracellular tenofovir diphosphate concentrations were explored among those receiving TDF. The mean age was 20.9 (standard deviation [SD], 2.0) years; 63% were male; and 52% were African American. Compared to the no-TDF group, the TDF group showed lower mean estimated glomerular filtration rates and tubular reabsorption of phosphate, as well as higher parathyroid hormone and 1,25-dihydroxy vitamin D [1,25-OH(2)D] levels. The highest quintile of plasma tenofovir concentrations was associated with higher vitamin D binding protein, lower free 1,25-OH(2)D, higher 25-OH vitamin D, and higher serum calcium. The highest quintile of intracellular tenofovir diphosphate concentration was associated with lower FGF23. Higher plasma tenofovir concentrations were associated with higher vitamin D binding protein and lower free 1,25-OH(2)D, suggesting a functional vitamin D deficiency explaining TDF-associated increased parathyroid hormone. The finding of lower FGF23 accompanying higher intracellular tenofovir diphosphate suggests that different mechanisms mediate TDF-associated changes in phosphate handling. Separate pharmacokinetic properties may be associated with distinct TDF toxicities: tenofovir with parathyroid hormone and altered calcium balance and tenofovir diphosphate with hypophosphatemia and FGF23 regulation.

IMPORTANCE(The clinical trial registration number for this study is NCT00490412 and is available online athttp://clinicaltrials.gov/ct2/show/NCT00490412.)
RALP1 Is a Rhoptry Neck Erythrocyte-Binding Protein of Plasmodium falciparum Merozoites and a Potential Blood-Stage Vaccine Candidate Antigen
Authors: Ito Daisuke , Hasegawa Tomoyuki , Miura Kazutoyo , Yamasaki Tsutomu , Arumugam Thangavelu U. , Thongkukiatkul Amporn , Takeo Satoru , Takashima Eizo , Sattabongkot Jetsumon , Han Eun-Taek , Long Carole A. , Torii Motomi , Tsuboi Takafumi
Published: September 2013

Erythrocyte invasion by merozoites is an obligatory stage of
Plasmodium
infection and is essential to disease progression. Proteins in the apical organelles of merozoites mediate the invasion of erythrocytes and are potential malaria vaccine candidates. Rhoptry-associated, leucine zipper-like protein 1 (RALP1) of
Plasmodium falciparum
was previously found to be specifically expressed in schizont stages and localized to the rhoptries of merozoites by immunofluorescence assay (IFA). Also, RALP1 has been refractory to gene knockout attempts, suggesting that it is essential for blood-stage parasite survival. These characteristics suggest that RALP1 can be a potential blood-stage vaccine candidate antigen, and here we assessed its potential in this regard. Antibodies were raised against recombinant RALP1 proteins synthesized by using the wheat germ cell-free system. Immunoelectron microscopy demonstrated for the first time that RALP1 is a rhoptry neck protein of merozoites. Moreover, our IFA data showed that RALP1 translocates from the rhoptry neck to the moving junction during merozoite invasion. Growth and invasion inhibition assays revealed that anti-RALP1 antibodies inhibit the invasion of erythrocytes by merozoites. The findings that RALP1 possesses an erythrocyte-binding epitope in the C-terminal region and that anti-RALP1 antibodies disrupt tight-junction formation, are evidence that RALP1 plays an important role during merozoite invasion of erythrocytes. In addition, human sera collected from areas in Thailand and Mali where malaria is endemic recognized this protein. Overall, our findings indicate that RALP1 is a rhoptry neck erythrocyte-binding protein and that it qualifies as a potential blood-stage vaccine candidate.
Small-Molecule Inhibitor of the Shigella flexneri Master Virulence Regulator VirF
Authors: Koppolu Veerendra , Osaka Ichie , Skredenske Jeff M. , Kettle Bria , Hefty P. Scott , Li Jiaqin , Egan Susan M.
Published: September 2013

VirF is an AraC family transcriptional activator that is required for the expression of virulence genes associated with invasion and cell-to-cell spread byShigella flexneri, including multiple components of the type three secretion system (T3SS) machinery and effectors. We tested a small-molecule compound, SE-1 (formerly designated OSSL_051168), which we had identified as an effective inhibitor of the AraC family proteins RhaS and RhaR, for its ability to inhibit VirF. Cell-based reporter gene assays withEscherichia coliandShigella, as well asin vitroDNA binding assays with purified VirF, demonstrated that SE-1 inhibited DNA binding and transcription activation (likely by blocking DNA binding) by VirF. Analysis of mRNA levels using real-time quantitative reverse transcription-PCR (qRT-PCR) further demonstrated that SE-1 reduced the expression of the VirF-dependent virulence genesicsA,virB,icsB, andipaBinShigella. We also performed eukaryotic cell invasion assays and found that SE-1 reduced invasion byShigella. The effect of SE-1 on invasion required preincubation ofShigellawith SE-1, in agreement with the hypothesis that SE-1 inhibited the expression of VirF-activated genes required for the formation of the T3SS apparatus and invasion. We found that the same concentrations of SE-1 had no detectable effects on the growth or metabolism of the bacterial cells or the eukaryotic host cells, respectively, indicating that the inhibition of invasion was not due to general toxicity. Overall, SE-1 appears to inhibit transcription activation by VirF, exhibits selectivity toward AraC family proteins, and has the potential to be developed into a novel antibacterial agent.
Mechanism of Homologous Recombination and Implications for Aging-Related Deletions in Mitochondrial DNA
Authors: Chen Xin Jie
Published: September 2013

Homologous recombination is a universal process, conserved from bacteriophage to human, which is important for the repair of double-strand DNA breaks. Recombination in mitochondrial DNA (mtDNA) was documented more than 4 decades ago, but the underlying molecular mechanism has remained elusive. Recent studies have revealed the presence of a Rad52-type recombination system of bacteriophage origin in mitochondria, which operates by a single-strand annealing mechanism independent of the canonical RecA/Rad51-type recombinases. Increasing evidence supports the notion that, like in bacteriophages, mtDNA inheritance is a coordinated interplay between recombination, repair, and replication. These findings could have profound implications for understanding the mechanism of mtDNA inheritance and the generation of mtDNA deletions in aging cells.
Paediatric autoimmune liver disease
Authors: Mieli-Vergani Giorgina , Vergani Diego
Published: September 2013

Autoimmune liver disorders in childhood include autoimmune hepatitis (AIH) and AIH/sclerosing cholangitis overlap syndrome (henceforth referred to as autoimmune sclerosing cholangitis, ASC). These inflammatory liver disorders are characterised histologically by interface hepatitis, biochemically by elevated transaminase levels, and serologically by autoantibodies and increased levels of immunoglobulin G. AIH is particularly aggressive in children and progresses rapidly unless immunosuppressive treatment is started promptly. With appropriate treatment, 80% of patients achieve remission and long-term survival. For non-responders and difficult-to-treat patients, novel and more effective therapeutic approaches are sought. ASC responds to the same treatment used for AIH in regards to parenchymal inflammation, but bile duct disease progresses in about 50% of cases, leading to a worse prognosis and a higher liver transplantation requirement; moreover, it has a high recurrence rate after transplant. Progression of liver disease and recurrence after transplant are more common in patients with associated poorly controlled inflammatory bowel disease. Though the mechanisms underlying the pathogenesis of liver autoimmunity are not fully understood, genetic and environmental factors are likely to be involved. A deeper understanding of the pathogenesis of these conditions will contribute to the development of novel treatments, aimed ultimately at the restoration of tolerance to liver-derived antigens.