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PURPOSE: Using a sample of 20,445 Dutch twins, this study examined the relationship between speech fluency and attentional regulation in children. A secondary objective was to identify etiological overlap between nonfluency and poor attention using fluency-discordant twin pairs., METHOD: Three fluency groups were created at age 5 using a parent questionnaire: (a) probable stuttering (PS; N=826; 4.0%), highly nonfluent (HNF; N=547; 2.7%), and typically fluent (TF; N=19,072; 93%). Multiple scales assessing attention, primarily self-regulation/inhibition, were obtained from both parents when children were ages 5 and 7 and from teachers when children were age 7., RESULTS: When compared with the TF controls, both the PS and HNF children received higher (i.e., more problematic) scores on parental attention ratings at both ages (p<.002). Effect sizes were moderate for both groups. Teacher and parent ratings were generally comparable. The discordant co-twin analyses suggested that nonfluency and attention were influenced by potentially overlapping genetic and shared environmental factors., CONCLUSIONS: The liability to express both high nonfluency and problems with self-regulation/inhibition may arise from a common set of pathogenic mechanisms. This supports emerging models of stuttering, which propose that poor fluency may be part of a broader network of impaired self-regulatory processes.

PURPOSE: The purpose of this investigation was to examine the impact of Chromosome 4p- syndrome on the communication and expressive language phenotype of a large cross-cultural population of children, adolescents, and adults., METHOD: A large-scale survey study was conducted and a descriptive research design was used to analyze quantitative and qualitative data regarding the communication and expressive language manifestations of 200 children, youth, and adults from 16 countries and Puerto Rico who had been diagnosed with 4p conditions, including Wolf-Hirschhorn syndrome (WHS), Pitt-Rogers-Danks syndrome (PRDS), Proximal 4p Deletion syndrome, and complex chromosomal rearrangements associated with 4p-., RESULTS: Individuals with Chromosome 4p- syndrome represent a heterogeneous population with complex phenotypic profiles. The majority of the participants exhibited communication and expressive language skills below the 36-month developmental functioning level. A relatively small cohort of the study population exhibited advanced expressive language skills, a finding not reported in the professional literature., CONCLUSION: Results broaden the spectrum of expressive language skills associated with Chromosome 4p- syndrome and highlight the communication potential of a subset of individuals with 4p abnormalities for development of advanced language structures. It is hypothesized that the largest 4p deletion, which includes the 4p16.3 band and contiguous gene regions, results in the most severely affected expressive language phenotype.

Purpose: Behavioral genetic studies of speech fluency have focused on participants who present with clinical stuttering. Knowledge about genetic influences on the development and regulation of normal speech fluency is limited. The primary aims of this study were to identify the heritability of stuttering and high nonfluency and to assess the relative contribution of genetic and environmental factors to the correlation between these 2 fluency phenotypes. Method: Information on 6 specific speech fluency behaviors was obtained by maternal report for over 10,500 5-year-old Dutch twin pairs. Results: Genetic analyses revealed that both fluency phenotypes were moderately heritable, with heritability estimates of 42% and 45% for probable stuttering and high nonfluency, respectively. Shared environmental factors were also significant, explaining 44% of the individual differences in probable stuttering and 32% in nonfluency. For both phenotypes, the magnitude of the genetic and environmental influences did not differ between boys and girls. The overlap between the 2 traits was substantial (tetrachoric correlation was .72). A bivariate genetic analysis showed that this overlap was due to both overlapping genetic and environmental influences. Conclusions: These findings provide a foundation to justify further studies in normal fluency control, a scientific area that has received little cross-disciplinary attention.

This investigation examined the listening comprehension (LC) performance of two groups of adolescent struggling readers, one group with word-finding difficulties (WFD) and one with no word-finding difficulties (NWFD). Of interest was whether the expressive language difficulties of the WFD group would interfere with their success on a LC assessment that requires oral responses to complete. Findings indicated that whereas the performance of the WFD group was comparable with the NWFD group when LC was measured using a multiple-choice response format, their performance was significantly poorer when LC was measured using an open-ended verbal response format, suggesting that learners' WFD could interfere with their success on such assessments. Practical implications of these findings for the assessment of LC as part of adolescents' reading evaluations are discussed. © 2010 Hammill Institute on Disabilities.

(Chemical Equation Presented). Bismuth chloride was used to catalyze the [2 + 3] cycloaddition between sodium azide with aryl nitriles, aliphatic nitriles, and vinyl nitriles. A number of 5-substituted 1H-tetrazoles were synthesized in water or isopropanol/water mixtures using microwave heating. Good yields were obtained for these reactions when heated for 1 h at 120-160°C in a 3:1 isopropanol/water mixture. A few of the less reactive nitriles required longer reaction times for good yields. © Taylor & Francis Group, LLC.

Several 5-substituted 1H-tetrazoles were prepared in water or isopropanol/water mixtures using microwave heating. Good yields were obtained for the [2 + 3] cycloaddition of sodium azide with aryl nitriles, aliphatic nitriles, and vinyl nitriles when catalyzed by scandium triflate. The reactions were typically heated for 1 h at 160 °C in a 3:1 isopropanol/water mixture to obtain the best yields. © 2015 Taylor & Francis Group, LLC.

Various 5-substituted 1H-tetrazoles were synthesized from aryl nitriles, alkyl nitriles, and vinyl nitriles reacting with sodium azide. The tetrazoles were recovered in high yield under mild conditions when the reaction was catalyzed by ytterbium triflate hydrate in dimethylformamide. Other rare-earth and post-transition metal catalysts were also investigated. © 2014 Elsevier Ltd. All rights reserved.

Student self-assessment surveys were used to assess student study methods in organic chemistry courses. Surveys were given after examinations in the courses. Students that performed well on exams accurately predicted their exam scores. Students that did poorly were significantly off in their expectations.

Olfactory receptor neurons in Atlantic salmon (Salmo salar) appear to use a phosphoinositide-directed phospholipase C (PLC) in odorant signal transduction. The consequences of odor-activated PLC depend on its product, inositol 1,4,5-trisphosphate (IP3). Therefore, a plasma membrane rich (PMR) fraction, previously characterized from salmon olfactory rosettes, was used to study binding sites for IP3 and its phosphorylation product, inositol 1,3,4,5-tetrakisphosphate (IP4). Binding sites for IP3 were present at the lower limit for detection in the PMR fraction but were abundant in a microsomal fraction. Binding sites for IP4 were abundant in the PMR fraction and thus colocalized in the same subcellular fraction with odorant receptors for amino acids and bile acids. Binding of IP4 was saturable and high affinity (K d = 83 nM). The rank order for potency of inhibition of IP4 by other inositol polyphosphates (InsP x ) followed the phosphorylation number with InsP6 > InsP5 > other InsP4 isomers > InsP3 isomers > InsP2 isomers, with the latter showing no activity. The consequences of PLC activity in this system may be dictated in part by a putative receptor for IP4.

In the complete-basis-set (CBS) model chemistries, an interference correction is added to the total energy. It is added because the CBS-type extrapolation to the basis-set limit of second-order Møller–Plesset (MP2) perturbation theory usually overestimates the magnitude of the basis-set truncation error at higher levels of electron-correlation treatment. In this Letter, the question is pursued whether the CBS-type interference correction could also improve the computational results when the MP2 basis set limit is approached by means of explicitly-correlated MP2 theory using Slater-type geminals.

We present a quantitative model for predicting the level of difficulty subjects will experience with specific problems. The model explicitly accounts for the number of subproblems a problem can be broken into and the difficultly of each subproblem. Although the model builds on previously published models, it is uniquely suited for blending with qualitative methods for the study of problem-solving processes rather than being limited to examination of final answers only. We illustrate the usefulness of the model by analysing the written solutions and think-aloud protocols of 17 subjects engaged with 25 chemical stoichiometry problems. We find that familiar themes for subject difficulty are revealed, including mapping of surface features, lack of interconnected knowledge hierarchy, and algorithmic operations at the expense of conceptual understanding.

Aims: Loline alkaloids produced by Epichloë spp. are known to deter feeding by insect herbivores while also serving as a significant carbon source for certain epiphytic bacteria on tall fescue leaves. In this study we examined the role of loline alkaloids in attracting certain bacteria to the rhizosphere of tall fescue plants that harbor loline producing fungal endophytes. Methods: Population studies were used to compare the fitness of known loline catabolizing strains to other rhizosphere bacteria. Pyrosequencing of 16S rRNA fragments compared the composition of bacterial communities inhabiting the endophyte infected tall fescue (Festuca arundinacea) rhizosphere to those of endophyte free fescue plants. Results: Rhizosphere population studies demonstrated that loline catabolizing strains Burkholderia ambifaria 7R and Pseudomonas aureofaciens outcompete and suppress the growth of non-loline catabolizing strains. Pyrosequencing of 16S rRNA fragments showed greater percentages of certain plant growth promoting bacteria in rhizosperes seeded with B. ambifaria 7R than non-inoculated soils. Rhizospheres of endophyte infected plants showed higher species richness (Shannon diversity index = 4.03) over endophyte free rhizospheres (Shannon diversity index = 3.08) and a greater percentage of Firmicutes. Conclusions: The differences in microbial community composition between endophyte-infected and endophyte-free rhizospheres suggest that the presence of fungal endophytes influences microbial community structure. Loline alkaloid production may be one proxy by which the fungal endophyte shapes microbial communities, as evidenced by increased fitness of loline catabolizing bacteria in the tall fescue rhizosphere. © 2015, Springer International Publishing Switzerland.

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adaptive immunity. Here we highlight specific biological processes that could be exploited as targets for the prevention and therapy of cancer. Specifically, we describe how inhibition of targets such as cholesterol synthesis and metabolites, reactive oxygen species and hypoxia, macrophage activation and conversion, indoleamine 2,3-dioxygenase regulation of dendritic cells, vascular endothelial growth factor regulation of angiogenesis, fibrosis inhibition, endoglin, and Janus kinase signaling emerge as examples of important potential nexuses in the regulation of tumorigenesis and the tumor microenvironment that can be targeted. We have also identified therapeutic agents as approaches, in particular natural products such as berberine, resveratrol, onionin A, epigallocatechin gallate, genistein, curcumin, naringenin, desoxyrhapontigenin, piperine, and zerumbone, that may warrant further investigation to target the tumor microenvironment for the treatment and/or prevention of cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.