bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial Testing (Stage 1) of MK‐8242—A Novel MDM2 Inhibitor—by the Pediatric Preclinical Testing Program
Authors: Kang Min H. , Reynolds C. Patrick , Kolb E. Anders , Gorlick Richard , Carol Hernan , Lock Richard , Keir Stephen T. , Maris John M. , Wu Jianwrong , Lyalin Dmitry , Kurmasheva Raushan T. , Houghton Peter J. , Smith Malcolm A. 
Published: May 2016

BackgroundMK‐8242 is an inhibitor of MDM2 that stabilizes the tumor suppressor TP53 and induces growth arrest or apoptosis downstream of TP53 induction.ProceduresMK‐8242 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro cell line panel at concentrations from 1.0 nM to 10.0 μM and against the PPTP in vivo xenograft panels using oral gavage on Days 1–5 and Day 15–19 at a dose of 125 mg/kg (solid tumors) or 75 mg/kg (acute lymphoblastic leukemia [ALL] models).ResultsThe median IC50 for MK‐8242 was 0.07 μM for TP53 wild‐type cell lines versus >10 μM for TP53 mutant cell lines. MK‐8242 induced a twofold or greater delay in time to event in 10 of 17 (59%) of TP53 wild‐type solid tumor xenografts, excluding osteosarcoma xenografts that have very low TP53 expression. Objective responses were observed in seven solid tumor xenografts representing multiple histotypes. For the systemic‐disease ALL panel, among eight xenografts there were two complete responses (CRs) and six partial responses (PRs). Two additional MLL‐rearranged xenografts (MV4;11 and RS4;11) grown subcutaneously showed maintained CR and PR, respectively. The expected pharmacodynamic responses to TP53 activation were observed in TP53 wild‐type models treated with MK‐8242. Pharmacokinetic analysis showed that MK‐8242 drug exposure in SCID mice appears to exceed that was observed in adult phase 1 trials.ConclusionsMK‐8242‐induced tumor regressions across multiple solid tumor histotypes and induced CRs or PRs for most ALL xenografts. This activity was observed at MK‐8242 drug exposures that appear to exceed those observed in human phase 1 trials.
Post‐polymerization modification of branched polyglycidol with N‐Hydroxy phthalimide to give ratio‐controlled amino‐oxy functionalized species
Authors: Beezer Dain B. , Harth Eva 
Published: May 2016

ABSTRACTRatio‐controlled amino‐oxy functionalized, branched polyglycidols are prepared by a post‐polymerizaton modification using and optimizing the Mitsunobu reaction for this purpose. The hydroxyl side‐groups are functionalized with N‐hydroxy phthalimide and the hydrazinolysis of this group furnishes a new class of branched polyglycidols with pendant amino‐oxy groups. Reproducible functionalization degrees of 17, 33, 43, and 63% of the hydroxyl groups are obtained via the presented developed methodology. MTT assays demonstrate the biocompatibility of amino‐oxy functionalized materials. With this, the prepared structural motifs are valuable precursors for the synthesis of biomaterials, bioconjugates and hydrogels in which orthogonal strategies are desired. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 2820–2825
Cancer negatively impacts on sexual function in adolescents and young adults: The AYA HOPE study
Authors: Wettergren Lena , Kent Erin E. , Mitchell Sandra A. , Zebrack Brad , Lynch Charles F. , Rubenstein Mara B. , Keegan Theresa H. M. , Wu Xiao‐Cheng , Parsons Helen M. , Smith Ashley Wilder ,   the AYA HOPE Study Collaborative Group
Published: May 2016

AbstractObjectiveThis cohort study examined the impact of cancer on sexual function and intimate relationships in adolescents and young adults (AYAs). We also explored factors predicting an increased likelihood that cancer had negatively affected these outcomes.MethodsParticipants (n = 465, ages 15–39) in the Adolescent and Young Adult Health Outcomes and Patient Experience (AYA HOPE) study completed two surveys approximately 1 and 2 years post‐cancer diagnosis. We used multivariable logistic regression to determine factors negatively affected by perceptions of sexual function at 2 years post‐diagnosis.ResultsForty‐nine percent of AYAs reported negative effects on sexual function at 1 year post‐cancer diagnosis and 70% of those persisted in their negative perceptions 2 years after diagnosis. Those reporting a negative impact at 2 years were more likely to be 25 years or older (OR, 2.53; 95% CI, 1.44–4.42), currently not raising children (OR, 1.81; 95% CI, 1.06–3.08), experiencing fatigue (OR, 0.99; 95% CI, 0.975–0.998) and more likely to report that their diagnosis has had a negative effect on physical appearance (OR, 3.08; 95% CI, 1.97–4.81). Clinical factors and mental health were not significant predictors of negative effects on sexual function.ConclusionsMany AYAs diagnosed with cancer experience a persistent negative impact on sexual life up to 2 years following diagnosis. The findings underscore the need to develop routine protocols to assess sexual function in AYAs with cancer and to provide comprehensive management in the clinical setting. Copyright © 2016 John Wiley & Sons, Ltd.
The assessment of metacognition in children aged 4–16 years: a systematic review
Authors: Gascoine Louise , Higgins Steve , Wall Kate 
Published: May 2016

This article presents the results of a systematic review of methods that have been used to measure or assess metacognition in children aged 4–16 years over a 20‐year period (1992–2012). It includes an overview of the types of tool and methods used linked with the ages of the participants targeted and how metacognition and associated concepts are defined. Two thousand, seven hundred and twenty‐one records were identified through systematic searching; 525 articles or reports were full text screened, resulting in 149 included studies reporting 84 distinct tools or methods. Of these 84 distinct tools or methods, four were excluded from further analysis after appraisal for reliability, validity and replicability. The final number of methods and tools for metacognitive assessment included in the analysis is 80. The key findings of this review include:

Self‐report measures (including questionnaires, surveys and tests) comprise 61% of the included tools;
Observational methods that do not rely on prompting to ‘think aloud’ (Think Aloud Protocols) have only been used with students aged 9 years and under;
Information about reliability and validity is not always given or given accurately for different tools and methods;
The definition of metacognition in a particular study relates directly to its assessment and therefore its outcomes: this can be misaligned.
Prediction model of time diversity using Japan rain radar data
Authors: Chodkaveekityada Peeramed , Fukuchi Hajime 
Published: May 2016

SummaryThe effects of rain attenuation on communication systems will become more pronounced in future satellite communication systems, especially with the planned use of the 21‐GHz band or higher‐frequency bands. Diversity techniques provide a solution to mitigate rain attenuation effects. This study proposes a time diversity technique, one such technique that is likely to demonstrate high effectiveness. To model the system, rainfall rate statistics are necessary, and reliability is improved as the amount of statistical data increases. This paper derives the cumulative distribution of the rainfall rate across Japan over 4 years using rain radar data from the automated meteorological data acquisition system and ground‐based rain radar network and evaluates the rainfall rate at 23 observation points across Japan. We carry out a performance evaluation for all locations within Japan to confirm the efficiency of the time diversity method. Finally, we propose prediction model of the time diversity gain for Japan and other significant parameter which is time correlation of rainfall rate that was found from the time diversity results for further investigation. Copyright © 2016 John Wiley & Sons, Ltd.
Calcium channel blockade attenuates abnormal synaptic transmission in the dentate gyrus elicited by entorhinal amyloidopathy
Authors: Gholami Pourbadie Hamid , Naderi Nima , Janahmadi Mahyar , Mehranfard Nasrin , Motamedi Fereshteh 
Published: May 2016

AbstractEntorhinal‐hippocampal network is one of the earliest circuits which is affected by Alzheimer's disease (AD). There are numerous data providing the evidence of synaptic deficit in the dentate gyrus (DG) of AD animal model. However, there is little known about how entorhinal cortex (EC) amyloidophaty affects each excitatory and/or inhibitory transmission in the early stage of AD. On the other hand, it is believed that calcium dyshomeostasis has a critical role in the etiology of AD. Here, the effect of the EC amyloid pathogenesis on excitatory or inhibitory post synaptic currents (EPSC and IPSC, respectively) in the DG granule cells and then the possible neuroprotective action of L‐type calcium channel blockers (CCBs), nimodipine and isradipine, were examined. The amyloid beta (Aβ) 1–42 was injected bilaterally into the EC of male rats and one week later, synaptic currents in the DG granule cells were assessed by whole cell patch clamp. EPSCs were evoked by stimulating the perforant pathway. Voltage clamp recording showed profound decrease of evoked EPSC amplitude and paired pulse facilitation in the DG granule cells of Aβ treated rats. Furthermore, AMPA/NMDA ratio was significantly decreased in the Aβ treated animals. On the other hand, amplitude of IPSC currents was significantly increased in the DG granule cells of these animals. These modifications of synaptic currents were partially reversed by daily intracerebroventricular administration of isradipine or nimodipine. In conclusion, our results suggest that Aβ in the EC triggers decreased excitatory transmission in the DG with substantial decrement in AMPA currents, leading to a prominent activity of inhibitory circuits and increased inhibition of granule cells which may contribute to the development of AD‐related neurological deficits in AD and treatment by CCBs could preserve normal synaptic transmission against Aβ toxicity.
Teaching and Learning in the Global Village: Connect, Create, Collaborate, and Communicate
Authors: Dwyer Bernadette 
Published: May 2016

AbstractThe world is increasingly interconnected through technology. In order to live and work in a global village our students need to develop global literacy. Global literacy incorporates a range of overlapping concepts including an advocacy dimension, global citizenship responsibility, and cultural and linguistic awareness. Further, global literacy encompasses a multiplicity of literacies and is grounded in social, cultural, political, and historical practices and events. The article discusses how educators can harness the power of technology to engage their students in authentic literacy events and practices designed to promote the knowledge, skills, and dispositions that students require to develop global literacy in the 21st century. Initiatives and projects designed to create global literacy are described in areas such as connecting communities of readers and writers; creating cultural understanding through literature and folklore; communicating across time and space; and collaborating with learning partners across the globe.
Statistical learning and the critical period: how a continuous learning mechanism can give rise to discontinuous learning
Authors: Thiessen Erik D. , Girard Sandrine , Erickson Lucy C. 
Published: May 2016

Infants and children are generally more successful than adults in learning novel languages, a phenomenon referred to as acriticalorsensitiveperiod for language acquisition. One explanation for this critical period is the idea that children have access to a set of language learning processes or mechanisms unavailable to adults. From this perspective, developmental change is explained in terms of a discontinuity of learning processes. We suggest that this is not the only possible explanation for developmental change in language learning outcomes. Instead, we propose that the mechanisms underlying language acquisition (in particular, we highlight statistical learning) are largely continuous across the lifespan. From this perspective, developmental change is explained in terms of experience, differences in the input with age, and maturational changes in the cognitive architecture supporting learning, even while the learning process itself operates continuously across developmental time.WIREs Cogn Sci2016, 7:276–288. doi: 10.1002/wcs.1394This article is categorized under:Linguistics > Language AcquisitionPsychology > Language
Altered development and function of the placental regions in preeclampsia and its association with long‐chain polyunsaturated fatty acids
Authors: Rani Alka , Wadhwani Nisha , Chavan‐Gautam Preeti , Joshi Sadhana 
Published: May 2016

The placenta is an essential organ formed during pregnancy that mainly transfers nutrients from the mother to the fetus. Nutrients taken up by the placenta are required for its own growth and development and to optimize fetal growth. Hence, placental function is an important determinant of pregnancy outcome. Among various nutrients, fatty acids, especially long‐chain polyunsaturated fatty acids (LCPUFAs), including omega 3 and omega 6 fatty acids, are essential for placental development from the time of implantation. Studies have associated these LCPUFAs with placental development through their roles in regulating oxidative stress, angiogenesis, and inflammation, which may in turn influence their transfer to the fetus. The placenta has a heterogeneous morphology with variable regional vasculature, oxidative stress, and LCPUFA levels in healthy pregnancies depending upon the location within the placenta. However, these regional structural and functional parameters are found to be disturbed in pathological conditions, such as preeclampsia (PE), thereby affecting pregnancy outcome. Hence, the alterations in LCPUFA metabolism and transport in different regions of the PE placenta as compared with normal placenta could potentially be contributing to the pathological features of PE. The regional variations in development and function of the placenta and its possible association with placental LCPUFA metabolism and transport in normal and PE pregnancies are discussed in this review. WIREs Dev Biol 2016, 5:582–597. doi: 10.1002/wdev.238This article is categorized under:

Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing
Early Embryonic Development > Fertilization to Gastrulation
Vertebrate Organogenesis > Musculoskeletal and Vascular
Role of frameshift ubiquitin B protein in Alzheimer's disease
Authors: Chen Xin , Petranovic Dina 
Published: May 2016

Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by accumulation of misfolded and aggregated proteins. Since the ubiquitin‐proteasome system (UPS) is the major intracellular protein quality control (PQC) system in eukaryotic cells, it is likely involved in the etiology of AD. The frameshift form of ubiquitin (Ubb+1) accumulates in the neuritic plaques and neurofibrillary tangles in patients with AD. Ubb+1 accumulates in an age‐dependent manner as a result of RNA‐polymerase mediated molecular misreading during transcription, which allows the formation of mutant proteins in the absence of gene mutations. The accumulation of the Ubb+1 protein may act as an endogenous reporter for proteasome dysfunction and a growing number of studies have shown that Ubb+1 may play more important pathogenic roles in AD etiology than previously hypothesized. The yeast Saccharomyces cerevisiae shares many conserved biological processes with all eukaryotic cells, including human neurons. This organism has been regarded as a model system for investigating the fundamental intracellular mechanisms, including those underlying neurodegeneration. We propose here that yeast systems biology approaches, combined with cell and molecular biology approaches will increase the relevant knowledge needed for advancement and elucidation of mechanisms and complex traits, which could provide new targets for therapeutic intervention in AD. WIREs Syst Biol Med 2016, 8:300–313. doi: 10.1002/wsbm.1340This article is categorized under:

Models of Systems Properties and Processes > Organismal Models
Cluster Helix Structure of the Binary Compound W5I12
Authors: Ströbele Markus , Meyer H.‐Jürgen 
Published: May 2016

AbstractThe binary tungsten iodide W5I12 forms an unprecedented one‐dimensional helical structure. A crystal structure refinement performed on basis of X‐ray powder diffraction data revealed the space group P61 [Z = 6, a = 993.97(2) pm, c = 4226.73(9) pm]. The crystal structure is based on [(W5I8i)I3aI2/2a‐a] clusters, interconnected by two shared apical iodido ligands to form helical chain arrangements.
From structural biology to designing therapy for inborn errors of metabolism
Authors: Yue Wyatt W. 
Published: May 2016

AbstractAt the SSIEM Symposium in Istanbul 2010, I presented an overview of protein structural approaches in the study of inborn errors of metabolism (Yue and Oppermann 2011). Five years on, the field is going strong with new protein structures, uncovered catalytic functions and novel chemical matters for metabolic enzymes, setting the stage for the next generation of drug discovery. This article aims to update on recent advances and lessons learnt on inborn errors of metabolism via the protein‐centric approach, citing examples of work from my group, collaborators and co‐workers that cover diverse pathways of transsulfuration, cobalamin and glycogen metabolism. Taking into consideration that many inborn errors of metabolism result in the loss of enzyme function, this presentation aims to outline three key principles that guide the design of small molecule therapy in this technically challenging field: (1) integrating structural, biochemical and cell‐based data to evaluate the wide spectrum of mutation‐driven enzyme defects in stability, catalysis and protein‐protein interaction; (2) studying multi‐domain proteins and multi‐protein complexes as examples from nature, to learn how enzymes are activated by small molecules; (3) surveying different regions of the enzyme, away from its active site, that can be targeted for the design of allosteric activators and inhibitors.
Insights into a million-year-scale Rhenohercynian carbonate platform evolution through a multi-disciplinary approach: example of a Givetian carbonate record from Belgium
Authors: PAS D. , DA SILVA A. C. , DEVLEESCHOUWER X. , DE VLEESCHOUWER D. , CORNET P. , LABAYE C. , BOULVAIN F. 
Published: May 2016

AbstractIn this paper we formulate answers to three important questions related to Givetian carbonate records and their use for reconstructing million-year-scale past palaeoenvironmental changes. First, we provide detailed illustrations of the fascinating diversity that shaped a significant shallow reefal platform during early to late Givetian time in the Rhenohercynian Ocean; secondly we improve the sedimentological model of the extensive Givetian carbonate platform in the Dinant Basin; and thirdly we evaluate the application of magnetic susceptibility as a tool for long-term trend correlations and palaeoenvironmental reconstructions. These goals are reached by making a sedimentological, geophysical and geochemical study of the La Thure section. Through the early–late Givetian interval we discerned 18 microfacies ranging from a homoclinal ramp to a discontinuously rimmed shelf and then a drowning shelf. The comparison of these sedimentological results with those published for the south of the Dinant Syncline allowed us to provide an up to date model of the vertical and lateral environmental development of one of the largest Givetian carbonate platforms in Europe. This comparison also increased the knowledge on the distribution of facies belts in the Dinant Basin and allowed us to highlight the Taghanic Event. Palaeoredox proxies reveal a substantial change in the oxygenation level, from oxygen-depleted to more oxic conditions, between middle and late Givetian time. We demonstrated the relationship between variation in magnetic susceptibility values and proxies for siliciclastic input (such as Si, Al). The La Thure section is considered a key section for the understanding of internal shelf settings bordering Laurussia's southeastern margin.
Carbon-isotope anomalies and demise of carbonate platforms in the Sinemurian (Early Jurassic) of the Tethyan region: evidence from the Southern Alps (Northern Italy)
Authors: MASETTI DANIELE , FIGUS BILLY , JENKYNS HUGH C. , BARATTOLO FILIPPO , MATTIOLI EMANUELA , POSENATO RENATO 
Published: May 2016

AbstractDespite its global impact on ecosystems, the Triassic/Jurassic boundary event had only a modest effect on the carbonate depositional systems of the Southern Alps, whereas a fundamental reorganization of the same palaeogeographic area took place during the Sinemurian Age. This paper investigates whether or not the well-documented demise of Sinemurian carbonate platforms in the Tethyan region was a response to a global event by examination of carbon-isotope anomalies in successions of different facies that record this interval of time. A chemostratigraphic transect from Lake Garda up to the eastern Italian border is illustrated by four stratigraphic sections; high-resolution (20 cm over key intervals) chemostratigraphic sampling allowed detection of a major negative δ13C anomaly of ~ 1.5‰, preceded by a positive excursion, both in shallow- and deep-water successions, over the stratigraphical range of the ammonite genusArnioceras. A comparison with sections from the UK suggests that the positive excursion belongs to theturneriZone and the succeeding negative excursion falls within theobtusumZone. In the deep-water Belluno Basin, the negative anomaly occurs in a biogenic chert-rich unit recording the onset of mesotrophic conditions in the basin. In the platform-carbonate successions, this major negative carbon-isotope excursion is developed within a calcarenitic unit corresponding to the lowest occurrence of the foraminiferPaleomayncina termieri. This evidence for deepening and transgression across the carbonate platform suggests pre-conditioning for drowning. Hence, rather than tectonic subsidence alone, environmental factors may have aided the demise of Tethyan carbonate platforms during the Early Jurassic Sinemurian Age.
A simple proof of Gauss's inequality.
Authors: Perks Wilfred 
Published: May 2016

Consider a continuous probability distribution of a variablexmeasured from its mean in units of its standard deviation, and suppose that deviations from the mean are taken irrespective of sign; letpxrepresent the ordinate applicable tox(this ordinate is, of course, the sum of the original ordinates at +xand —x). We then have, and we write.
The Impact of Holy Land Crusades on State Formation: War Mobilization, Trade Integration, and Political Development in Medieval Europe
Authors: Blaydes Lisa , Paik Christopher 
Published: May 2016

AbstractHoly Land Crusades were among the most significant forms of military mobilization to occur during the medieval period. Crusader mobilization had important implications for European state formation. We find that areas with large numbers of Holy Land crusaders witnessed increased political stability and institutional development as well as greater urbanization associated with rising trade and capital accumulation, even after taking into account underlying levels of religiosity and economic development. Our findings contribute to a scholarly debate regarding when the essential elements of the modern state first began to appear. Although our causal mechanisms—which focus on the importance of war preparation and urban capital accumulation—resemble those emphasized by previous research, we date the point of critical transition to statehood centuries earlier, in line with scholars who emphasize the medieval origins of the modern state. We also point to one avenue by which the rise of Muslim military and political power may have affected European institutional development.