bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fold or hold: experimental evolution in vitro
Authors: Collins S. , Rambaut A. , Bridgett S. J. 
Published: September 2013

AbstractWe 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

AbstractHepatocellular 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.
Failure of Intralesional Propranolol in Infantile Hemangiomas
Authors: Torres‐Pradilla Mauricio , Baselga Eulalia 
Published: September 2013

AbstractThe 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

AbstractBackgroundNimotuzumab, 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.MethodsFourteen 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.ResultsA 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.ConclusionsMRI/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

AbstractBackgroundThe 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.MethodsThe 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.ResultsThe 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).ConclusionThe 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

AbstractThe 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

SummaryBackgroundCatechol‐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.MethodsAn 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.ResultsBefore 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.ConclusionPsoriasis 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

AbstractSpiny 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

ContentsStrategic 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

AbstractIn 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

AbstractIn 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

SummaryThe 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

SummaryOxalate‐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.
Pharmacokinetic and Pharmacodynamic Considerations in Antimalarial Dose Optimization
Authors: White Nicholas J. 
Published: September 2013

ABSTRACT

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.